Inside Maloney's Brain

Here is a wonderful source evaluating different alternative autism treatments.

In summary:  just as non-autistic children can benefit from a good diet (by which I mean something dramatically different from the S.A.D., or Standard American Diet), studies indicate that diet plays a profound role in the brain development of autistic children. 

Aliment Pharmacol Ther. 2002 Apr;16(4):663-74.  Related Articles, Links 

Review article: the concept of entero-colonic encephalopathy, autism and opioid receptor ligands.

Wakefield AJ, Puleston JM, Montgomery SM, Anthony A, O'Leary JJ, Murch SH.

Inflammatory Bowel Disease Study Group, Centre for Gastroenterology, Department of Medicine, Royal Free and University College Medical School, London, UK. wakers@aol.com

There is growing awareness that primary gastrointestinal pathology may play an important role in the inception and clinical expression of some childhood developmental disorders, including autism. In addition to frequent gastrointestinal symptoms, children with autism often manifest complex biochemical and immunological abnormalities. The gut-brain axis is central to certain encephalopathies of extra-cranial origin, hepatic encephalopathy being the best characterized. Commonalities in the clinical characteristics of hepatic encephalopathy and a form of autism associated with developmental regression in an apparently previously normal child, accompanied by immune-mediated gastrointestinal pathology, have led to the proposal that there may be analogous mechanisms of toxic encephalopathy in patients with liver failure and some children with autism. Aberrations in opioid biochemistry are common to these two conditions, and there is evidence that opioid peptides may mediate certain aspects of the respective syndromes. The generation of plausible and testable hypotheses in this area may help to identify new treatment options in encephalopathies of extra-cranial origin. Therapeutic targets for this autistic phenotype may include: modification of diet and entero-colonic microbial milieu in order to reduce toxin substrates, improve nutritional status and modify mucosal immunity; anti-inflammatory/immunomodulatory therapy; and specific treatment of dysmotility, focusing, for example, on the pharmacology of local opioid activity in the gut.

Publication Types:

Review

Review, Tutorial

PMID: 11929383 [PubMed - indexed for MEDLINE]

Neuropsychopharmacology 2003 Jan;28(1):193-8          Related Articles, Links

Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders.

Hollander E, Novotny S, Hanratty M, Yaffe R, DeCaria CM, Aronowitz BR, Mosovich S.

Autism is a neurodevelopmental disorder characterized by dysfunction in three core behavioral domains: repetitive behaviors, social deficits, and language abnormalities. There is evidence that abnormalities exist in peptide systems, particularly the oxytocin system, in autism spectrum patients. Furthermore, oxytocin and the closely related peptide vasopressin are known to play a role in social and repetitive behaviors. This study examined the impact of oxytocin on repetitive behaviors in 15 adults with autism or Asperger's disorder via randomized double-blind oxytocin and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviors: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant reduction in repetitive behaviors following oxytocin infusion in comparison to placebo infusion. Repetitive behavior in autism spectrum disorders may be related to abnormalities in the oxytocin system, and may be partially ameliorated by synthetic oxytocin infusion.Neuropsychopharmacology (2003) 28, 193-198. doi:10.1038/sj.npp.1300021

PMID: 12496956 [PubMed - in process]

J Fam Health Care 2002;12(2):34-8     Related Articles, Links

Diet in autism and associated disorders.

Garvey J.

Royal Free Hospital, London.

A dietitian discusses the theory that peptides with opioid activity may cause or trigger autism. The use of an exclusion diet to treat autism is explained, weighing the potential benefits against some of the practical difficulties of keeping to a strict exclusion diet. The use of nutritional supplements is described. An abnormal gut flora has also been implicated in autism and the use of probiotics and prebiotics in improving the integrity of the gut mucosa is also discussed.

Publication Types:

•               Review

•               Review, Tutorial

PMID: 12415751 [PubMed - indexed for MEDLINE]

Neuropsychobiology 2002;46(2):76-84             Related Articles, Links

Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder.

Jyonouchi H, Sun S, Itokazu N.

Department of Pediatrics, University of Minnesota, Minneapolis, Minn, USA.

OBJECTIVES: Children with autism spectrum disorder (ASD) frequently reveal various gastrointestinal (GI) symptoms that may resolve with an elimination diet along with apparent improvement of some of the behavioral symptoms. Evidence suggests that ASD may be accompanied by aberrant (inflammatory) innate immune responses. This may predispose ASD children to sensitization to common dietary proteins (DP), leading to GI inflammation and aggravation of some behavioral symptoms. METHODS: We measured IFN-gamma, IL-5, and TNF-alpha production against representative DPs [gliadin, cow's milk protein (CMP), and soy] by peripheral blood mononuclear cells (PBMCs) from ASD and control children [those with DP intolerance (DPI), ASD siblings, and healthy unrelated children]. We evaluated the results in association with proinflammatory and counter-regulatory cytokine production with endotoxin (LPS), a microbial product of intestinal flora and a surrogate stimulant for innate immune responses. RESULTS: ASD PBMCs produced elevated IFN-gamma and TNF-alpha, but not IL-5 with common DPs at high frequency as observed in DPI PBMCs. ASD PBMCs revealed increased proinflammatory cytokine responses with LPS at high frequency with positive correlation between proinflammatory cytokine production with LPS and IFN-gamma and TNF-alpha production against DPs. Such correlation was less evident in DPI PBMCs. CONCLUSION: Immune reactivity to DPs may be associated with apparent DPI and GI inflammation in ASD children that may be partly associated with aberrant innate immune response against endotoxin, a product of the gut bacteria. Copyright 2002 S. Karger AG, Basel

Publication Types:

•               Clinical Trial

PMID: 12378124 [PubMed - indexed for MEDLINE]

Nutr Neurosci 2002 Sep;5(4):251-61  Related Articles, Links

A randomised, controlled study of dietary intervention in autistic syndromes.

Knivsberg AM, Reichelt KL, Hoien T, Nodland M.

Center for Reading Research, Stavanger University College, Norway. ann-mari.knivsberg@slf.his.no

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.

Publication Types:

•               Clinical Trial

•               Randomized Controlled Trial

PMID: 12168688 [PubMed - indexed for MEDLINE]

Nutr Neurosci 2001;4(1):25-37            Related Articles, Links

Reports on dietary intervention in autistic disorders.

Knivsber AM, Reichelt KL, Nodland M.

Center for Reading Research, Stavanger College, Norway. ann-mari.knivsberg@slf.his.no

Autism is a developmental disorder for which no cure currently exists. Gluten and/or casein free diet has been implemented to reduce autistic behaviour, in addition to special education, since early in the eighties. Over the last twelve years various studies on this dietary intervention have been published in addition to anecdotal, parental reports. The scientific studies include both groups of participants as well as single cases, and beneficial results are reported in all, but one study. While some studies are based on urinary peptide abnormalities, others are not. The reported results are, however, more or less identical; reduction of autistic behaviour, increased social and communicative skills, and reappearance of autistic traits after the diet has been broken.

Publication Types:

•               Review

•               Review, Tutorial

PMID: 11842874 [PubMed - indexed for MEDLINE]

J Autism Dev Disord 2000 Oct;30(5):463-9      Related Articles, Links

Comment in:

•               J Autism Dev Disord. 2000 Oct;30(5):471-3.

Metabolic approaches to the treatment of autism spectrum disorders.

Page T.

Department of Neurosciences, University of California, San Diego, USA.

Although the exact prevalence of metabolic abnormalities in autism spectrum disorders is unknown, several metabolic defects have been associated with autistic symptoms. These include phenylketonuria, histidinemia, adenylosuccinate lyase deficiency, dihydropyrimidine dehydrogenase deficiency, 5'-nucleotidase superactivity, and phosphoribosylpyrophosphate synthetase deficiency. When the metabolic consequences of an enzyme defect are well defined (e.g., phenylketonuria, 5'-nucleotidase superactivity), treatment with diet, drugs, or nutritional supplements may bring about a dramatic reduction in autistic symptoms. This review evaluates evidence for metabolic etiologies in autism spectrum disorders, as well as for the efficacy of dietary and vitamin treatments. The relationship between gastrointestinal abnormalities and autism spectrum disorders is also considered.

PMID: 11098885 [PubMed - indexed for MEDLINE]

Am J Psychiatry 1978 Apr;135(4):472-5            Related Articles, Links

The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study.

Rimland B, Callaway E, Dreyfus P.

The authors used data from an earlier nonblind study to identify 16 autistic-type child outpatients who had apparently improved when given vitamin B6 (pyridoxine). In a double-blind study each child's B6 supplement was replaced during two separate experimental trial periods with either a B6 supplement or a matched placebo. Behavior was rated as deteriorating significantly during the B6 withdrawal.

Publication Types:

•               Clinical Trial

•               Controlled Clinical Trial

PMID: 345827 [PubMed - indexed for MEDLINE]

Adrenal Checklist

A. Reformatting recent traumas. Write down your deepest feelings on four consecutive nights. 

B. Watching for exercise/exhaustion. Movement up to the point of exhaustion, not beyond.

C. Sleeping in 1 1/2 hour cycles. Even if you don’t sleep, sleep when you can in multiples.

D. Not expecting more energy than you have. Do not work to exhaustion. Taking breaks shortens healing.

E. Adaptogen herbs: astragalus, ginseng.

F. Licorice trial (cortisol maintaining).

G. Watching for insulin bumps and a decrease in adrenal function (sleeping after meals). Eat every two hours. 

H. DHEA prehormone for individuals with chronic fatigue. May become any hormone in the body.

I. 7 Keto DHEA prehormone directly linked to cortisol production. 

J. Methylprednisolone long acting adrenal hormone. (Prescription only). 

Summary: many things may work, but the hormonal basis is absolutely essential to address first. 

J Am Acad Dermatol. 2002 Aug;47(2):231-40.

Acne therapy: a methodologic review.

Lehmann HP, Robinson KA, Andrews JS, Holloway V, Goodman SN.

Source

Department of Pediatrics, Johns Hopkins School of Medicine and Bloomberg School of Public Health, USA.

Abstract

BACKGROUND: 

Acne is a very common problem with significant physical and psychological morbidity. The evidence basis for its treatment had not been systematically reviewed. Therefore, we performed an evidence review to provide researchers a basis for further studies, and to provide clinicians the background needed to interpret current and future clinical studies.

OBJECTIVE: 

We summarize the methodologic state of the acne literature in patients with acne who do not have complicating co-morbidities.

METHODS: 

This was an expert-advised literature synthesis. We used a structured literature search for English-language controlled trials in Cochrane CENTRAL, MEDLINE, OLDMEDLINE, HSTAT, CINAHL, and PsychInfo. Results underwent a structured data abstraction process, with review by at least 2 reviewers.

RESULTS: 

Out of 1588 unique articles, 250 articles (274 controlled trials) over the past 50 years were reviewed: 57 (21%) trials had at least one major weakness and no strengths; 125 (47%) trials had at least one major strength and at least one major weakness; 48 (18%) trials had at least one major strength, and no major weaknesses. The remaining 16 (6%) were of intermediate quality or did not provide enough information to make a determination. One fourth of studies did not report patient age; one fourth did not report on patient gender. Only 8% mentioned patient race; only 2% mentioned skin type; 0.4% mentioned diet; none scored sexual maturity or insurance status. There were 1237 outcomes. There were more than 25 methods of assessing acne severity and more than 19 methods for counting lesions. There were only two trials that formally assessed psychological outcomes. More than 140 treatments were tested in 251 comparisons.

CONCLUSION: 

Ranging over 50 years of research, the acne literature evidences great heterogeneity at all levels: patient characteristics, acne severity, outcome assessments, treatments, and comparisons. A list of methodologic recommendations is provided.

PMID: 12140469

J Womens Health (Larchmt). 2012 Feb;21(2):223-30. Epub 2011 Dec 15.

Acne vulgaris in women: prevalence across the life span.

Perkins AC, Maglione J, Hillebrand GG, Miyamoto K, Kimball AB.

Source

Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

BACKGROUND: 

Acne vulgaris is a common skin disease with a large quality of life impact, characterized by comedones, inflammatory lesions, secondary dyspigmentation, and scarring. Although traditionally considered a disease of adolescence, reports suggest it is also a disease of adults, especially adult women. Our objectives were to determine acne prevalence in a large, diverse group of women and to examine acne by subtype and in relation to other skin findings, measurements, and lifestyle factors.

METHODS: 

We recruited 2895 women aged 10-70 from the general population. Photographs were graded for acne lesions, scars, and dyspigmentation. Measurements were taken of sebum excretion and pore size, and survey data were collected.

RESULTS: 

Of the women studied, 55% had some form of acne: 28% had mild acne, and 27% had clinical acne, 14% of which was primarily inflammatory and 13% of which was primarily comedonal. Acne peaked in the teenage years, but 45% of women aged 21-30, 26% aged 31-40, and 12% aged 41-50 had clinical acne. Women with inflammatory acne were younger than those with comedonal acne (p≤0.001), and postmenopausal women had less acne than age-matched peers (p<0.0001). Acne was associated with facial hirsutism (p=0.001), large pores (p=0.001), and sebum excretion (p=0.002). Smokers had more, primarily comedonal, acne than nonsmokers.

CONCLUSIONS: 

The cross-sectional design precludes conclusions about progression of acne with age. Participation was restricted to women. The photographic nature of the study imposes general limitations. Techniques used in this study were not sufficiently sensitive to identify cases of subclinical acne. More than a quarter of women studied had acne, which peaked in the teens but continued to be prevalent through the fifth decade.

PMID: 22171979

Pak J Biol Sci. 2011 Jun 1;14(11):658-63.

Therapeutic effects of biguanide vs. statin in polycystic ovary syndrome: a randomized clinical trial.

Navali N, Pourabolghasem S, Fouladi RF, Nikpour MA.

Source

Department of Obstetrics and Gynecology, Women's Reproduction Health Research Center, Alzahra and Taleghani Hospitals, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Various classes of medication are currently being used in Polycystic Ovary Syndrome (PCOS) patients including the biguanides and the statins. However, their efficacies are rarely compared. This study aimed to compare efficacy ofa biguanide and a statin in treating PCOS. In a randomized double-blind clinical trial, 400 women with PCOS were recruited within 15 months in Taleghani Hospital. They randomly received either a biguanide (metformin 500 mg three times daily) or a statin (simvastatin 20 mg daily) for three consecutive months. Changes of clinical and laboratory variables were compared. In the biguanide group the serum glucose status (abnormal fasting and non-fasting sugar and insulin levels and percentage of hyperinsulinemic cases) and menstrual abnormalities improved significantly after treatment (p < 0.05). In the statin group the lipid profile status (abnormal total cholesterol, high and low density lipoproteins), C-Reactive Protein (CRP), serum dehydroepiandrosterone sulfate, hyperinsulinemia, severity of acne and menstrual abnormalities improved significantly after treatment (p < 0.05). Comparing the two groups, the improvements in fasting blood sugar and serum insulin levels were significantly better in the biguanide group (p = 0.04 for both parameters); whereas the improvements in serum total cholesterol (p < 0.001), low density lipoprotein (p < 0.001), CRP (p < 0.001) and acne status (p = 0.04) were significantly superior in the statin receivers. Based on these results, each medication is only effective on some aspects of the disease. Overall, the simvastatin was superior to metformin with regard to the number of beneficial effects.

PMID: 22235508

Cochrane Database Syst Rev. 2011 Oct 5;(10):CD008565.

Statins for women with polycystic ovary syndrome not actively trying to conceive.

Raval AD, Hunter T, Stuckey B, Hart RJ.

Source

Shrimati Kaumudiniben Health Outcome Research Group (SKHORG), Near Depala's Chora, Dhrangadhra, Gujrat, India, 363310.

Abstract

BACKGROUND: 

Statins, as lipid-lowering agents with pleiotropic actions, are likely not only to improve the dyslipidaemia associated with polycystic ovary syndrome but may also exert other beneficial metabolic and endocrine effects.

OBJECTIVES: 

To assess the efficacy and safety of statin therapy for women with polycystic ovary syndrome (PCOS) who are not actively trying to conceive.

SEARCH STRATEGY: 

We searched the following databases (from inception to week 1, July 2011): the Cochrane Menstrual Disorders and Subfertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and CINAHL. We handsearched relevant conference proceedings and references of the identified articles for additional studies. We also contacted experts for further studies in progress.

SELECTION CRITERIA: 

Randomised controlled trials (RCTs) comparing a statin versus placebo or statin in combination with another drug versus another drug alone in women with PCOS.

DATA COLLECTION AND ANALYSIS: 

Two review authors performed data collection and analysis independently.

MAIN RESULTS: 

Four trials fulfilled the criteria for inclusion. They comprised a total of 244 women with PCOS receiving 12 weeks or 6 weeks of treatment. Two trials (184 women randomised) studied the effects of simvastatin and two trials (60 women randomised) studied the effects of atorvastatin. There was no good evidence that statins improved menstrual regularity, spontaneous ovulation rate, hirsutism or acne, either alone or in combination with the combined oral contraceptive pill (OCP). Nor were there any significant effects on body mass index (BMI). Statins were effective in lowering testosterone levels (nmol/L) (mean difference (MD) -0.90, 95% CI -1.18 to -0.62, P < 0.00001, 3 RCTs, 105 women) when used alone or with the OCP. Statins also improved total cholesterol, low-density lipoprotein (LDL) and triglycerides but had no significant effect on high-density lipoprotein (HDL) levels, high sensitivity (HS) C-reactive protein (HS-CRP), fasting insulin or homeostatic model assessment (HOMA) insulin resistance. No serious adverse events were reported in any of the included studies.

AUTHORS' CONCLUSIONS: 

Although statins improve lipid profiles and reduce testosterone levels in women with PCOS, there is no evidence that statins improve resumption of menstrual regularity or spontaneous ovulation, nor is there any improvement of hirsutism or acne. There is a need for further research to be performed with large sample sizes and well-designed RCTs to assess clinical outcomes.

PMID: 21975784

J Cosmet Dermatol. 2011 Dec;10(4):294-300. doi: 10.1111/j.1473-2165.2011.00587.x.

Fractional CO2 laser for the treatment of acne scars.

Omi T, Kawana S, Sato S, Bonan P, Naito Z.

Source

Department of Dermatology, Queen's Square Medical Center, Yokohama, Japan. t.omi@queens-sq.or.jp

Abstract

BACKGROUND: 

Numerous reports have been published on skin rejuvenation by the so-called fractional laser device that delivers a laser beam in a dot form over a grid pattern.

AIMS: 

In this study, we characterized the effects of a fractional CO(2) laser on atrophic acne scars at the clinical and ultrastructural levels.

METHODS: 

Seven healthy adult Japanese volunteers (aged 32-46 years, mean 37.6, five men and two women of Fitzpatrick skin type III) were recruited for this study. A fractional CO(2) laser device, SmartXide DOT (DEKA, Florence, Italy), was used with irradiation parameters set as follows: output power 10 W, pulse width 600 μs, dot spacing 800 μm, and stack 2 (irradiation output power 0.91 J/cm(2) ). A clinical examination and punch biopsy of each subject was performed before and just after the irradiation, and also at week 3 after three irradiation sessions. The biopsy specimens were stained with toluidine blue and were examined ultrastructurally.

RESULTS: 

Clinical improvement of the atrophic acne scars was observed at week 3 after the third irradiation session in all cases compared with the condition before treatment. Histologically, outgrowths of many degenerated elastic fibers were observed as irregular rod-shaped masses in the superficial dermis prior to the treatment in the region of the acne scars. At week 3 after the third irradiation, the degenerated elastic fibers were no longer observed, and the elastic fibers were elaunin-like.

CONCLUSIONS: 

The fractional CO(2) laser is considered to be very effective for treating atrophic acne scars.

© 2011 Wiley Periodicals, Inc.

PMID: 22151938

J Cosmet Laser Ther. 2011 Dec;13(6):308-14.

Clinical efficacy of home-use blue-light therapy for mild-to moderate acne.

Gold MH, Sensing W, Biron JA.

Source

Gold Skin Care Center, Department of Dermatology, School of Nursing, Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN 37215, USA. goldskin@goldskincare.com

Abstract

INTRODUCTION: 

Blue-light light-emitting diode (LED) therapy has become widely used for the treatment of inflammatory acne. In this study we evaluated the efficacy of a home use blue-light LED application in improving lesions and shortening their time to clearance.

METHODS: 

This was an IRB approved randomized self-control study. For each patient (n = 30), 2 similar lesions, one of each side of the face were chosen for treatment with either a blue-light LED hand-held or sham device. Treatments (n = 4) were conducted twice daily in the clinic and lesions were followed-up till resolution. Reduction in blemishes size and erythema and the overall improvement were evaluated by both the physician and the patients. Time to lesion resolution was recorded.

RESULTS: 

There was a significant difference in the response of lesions to the blue-light LED application as opposed to the placebo in terms of reduction in lesion size and lesion erythema as well as the improvement in the overall skin condition (p < 0.025). Signs of improvement were observed as early as post 2 treatments. Time to resolution was significantly shorter for the blue-light LED therapy.

CONCLUSION: 

The results support the effectiveness of using blue-light LED therapy on a daily basis for better improvement and faster resolution of inflammatory acne lesions.

PMID: 22091799

J Cosmet Laser Ther. 2006 Jun;8(2):71-5.

Combination blue (415 nm) and red (633 nm) LED phototherapy in the treatment of mild to severe acne vulgaris.

Goldberg DJ, Russell BA.

Source

Skin Laser & Surgery Specialists of New York/New Jersey, and Department of Dermatology, Mount Sinai School of Medicine, New York, NY 10022, USA. drdavidgoldberg@skinandlasers.com

Abstract

BACKGROUND AND OBJECTIVE: 

Acne vulgaris represents both a challenge to the treating dermatologist and a major concern for the patient. Conventional treatments have proved inconsistent with often unacceptable side effects and high rates of recurrence. Non-thermal, non-laser, phototherapy for acne with a combination of blue and red light has recently attracted attention. The present study was designed to assess the efficacy of this combination phototherapy.

METHODS: 

Twenty-four subjects, Fitzpatrick skin types II-V, with mild to severe symmetric facial acne vulgaris were recruited for the study. Subjects were well matched at baseline in terms of both age and duration of acne. Subjects were treated over eight sessions, two per week 3 days apart, alternating between 415 nm blue light (20 minutes/session, 48 J/cm2) and 633 nm red light (20 minutes/session, 96 J/cm2) from a light-emitting diode (LED)-based therapy system. Patients received a mild microdermabrasion before each session. Acne was assessed at baseline and at weeks 2, 4, 8 and 12.

RESULTS: 

Twenty-two patients completed the trial. A mean reduction in lesion count was observed at all follow-up points. At the 4-week follow-up, the mean lesion count reduction was significant at 46% (p=0.001). At the 12-week follow-up, the mean lesion count reduction was also significant at 81% (p=0.001). Patient and dermatologist assessments were similar. Severe acne showed a marginally better response than mild acne. Side effects were minimal and transitory. Comedones did not respond as well as inflammatory lesions.

CONCLUSIONS: 

Combination blue and red LED therapy appears to have excellent potential in the treatment of mild to severe acne. Treatment appears to be both pain- and side effect-free.

PMID: 16766484

Hum Fertil (Camb). 2011 Dec;14(4):261-5. doi: 10.3109/14647273.2011.632058.

Full investigation of patients with polycystic ovary syndrome (PCOS) presenting to four different clinical specialties reveals significant differences and undiagnosed morbidity.

Sivayoganathan D, Maruthini D, Glanville JM, Balen AH.

Source

The Leeds Centre for Reproductive Medicine, Seacroft Hospital, Leeds, UK.

Abstract

OBJECTIVE: 

This study aimed to compare the spectrum of polycystic ovary syndrome (PCOS) symptoms in patients from four different specialist clinics.

DESIGN: 

A prospective cross-sectional observational study. Setting: The study was conducted at the infertility, gynaecology, endocrine and dermatology clinics at Leeds General Infirmary, U.K.

PATIENTS: 

Seventy women presenting with features of PCOS: 20 from infertility, 17 from gynaecology, 17 from dermatology and 16 from endocrine clinics. Interventions: Participants were assessed for symptoms and signs of PCOS and underwent a full endocrine and metabolic profile and a pelvic ultrasound scan.

RESULTS: 

All subjects had experienced menstrual problems, 81% were overweight, 86% had polycystic ovaries on ultrasound, 56% had hirsutism, 53% had acne, 23% had acanthosis nigricans, 16% had alopecia and 38% had previously undiagnosed impaired glucose tolerance (IGT) or diabetes. A significant difference between the four clinic groups existed with regard to menstrual patterns (p = 0.0234), frequency distribution of presenting symptoms and the percentages of patients with PCOS who had already been diagnosed as having PCOS (p = 0.0088).

CONCLUSION: 

This study emphasizes the importance of understanding the full spectrum of PCOS as presented to different specialty clinics. Not only is the syndrome under diagnosed but also are the significant associated morbidities such as IGT and type 2 diabetes. Different specialists need to appreciate the spectrum of health problems for women with PCOS that may extend beyond the specific symptoms that precipitated the initial referral.

PMID: 22088131

Clin Endocrinol (Oxf). 1999 Dec;51(6):779-86.

Polycystic ovaries and associated clinical and biochemical features in young women.

Michelmore KF, Balen AH, Dunger DB, Vessey MP.

Source

Division of Public Health and Primary Care, Institute of Health Sciences, Oxford, UK.

Abstract

OBJECTIVE: 

To determine the prevalence of polycystic ovaries as identified by ultrasound in a group of young, postmenarcheal women in the normal population, and to investigate how polycystic ovaries are related to the spectrum of clinical and biochemical symptoms associated with the polycystic ovary syndrome (PCOS).

DESIGN: 

Cross-sectional observational study.

SUBJECTS AND METHODS: 

Volunteers were recruited from two universities and two general practice surgeries in Oxford. 230 women aged 18-25 years participated. Information collected and measurements performed included: a menstrual history, anthropometric measurements, clinical observation of acne and hirsutism, transabdominal pelvic ultrasound, and biochemical analysis of a fasting blood sample.

MAIN OUTCOME MEASURES: 

Prevalence of polycystic ovaries and their association with symptoms of the polycystic ovary syndrome.

RESULTS: 

Polycystic ovarian morphology was identified in 74 (33%, 95% CI = 27-39%) of the 224 women who attended for an ultrasound scan. In the non-users of hormonal contraception, irregular menstrual cycles were 20% more common in women with polycystic ovaries than in women with normal ovaries (P = 0.07). There were no significant differences in acne, hirsutism, body mass index or body fat percentage between women with polycystic and normal ovaries. Analysis of biochemical data showed that women with polycystic ovaries had higher total serum testosterone concentrations (P = 0.03). The prevalence of PCOS in this age group was as low as 8% or as high as 26% depending on which criteria were applied to define the syndrome. Sub-group analyses of women according to ovarian morphology and features of PCOS revealed greater mean BMI in women with PCOS, and also indicated lower fasting insulin concentrations and greater insulin sensitivity in polycystic ovary and PCOS groups when compared to women with normal ovaries.

CONCLUSIONS: 

Polycystic ovaries are very common in this age group but are not necessarily associated with other symptomatology. The prevalence of polycystic ovary syndrome varies widely according to the definition applied. Sub-group analysis of women with polycystic ovaries according to the presence or absence of features of polycystic ovary syndrome does not reveal an increasing trend for progression of endocrine abnormalities usually associated with polycystic ovary syndrome.

PMID: 10619984

Indian J Dermatol Venereol Leprol. 2011 Nov-Dec;77(6):688-94.

Oral isotretinoin in different dose regimens for acne vulgaris: a randomized comparative trial.

Agarwal US, Besarwal RK, Bhola K.

Source

Department of Dermatology, SMS Medical College and Hospital, Jaipur, Rajasthan, India. dr.usag@gmail.com

Abstract

BACKGROUND: 

Oral isotretinoin is recommended for severe nodulocystic acne in the doses of 1-2 mg/kg/day which is usually associated with higher incidence of adverse effects. To reduce the incidence of side-effects and to make it more cost-effective, the lower dose regimen of isotretinoin has been used.

AIM: 

To compare the efficacy and tolerability of oral isotretinoin in daily, alternate, pulse and low-dose regimens in acne of all types and also to assess whether it can be used for mild and moderate acne also.

METHODS: 

One hundred and twenty patients with acne were randomized into four different treatment regimens each consisting of 30 patients. Group A was prescribed isotretinoin 1 mg/kg/day, Group B 1 mg/kg alternate day, Group C 1 mg/kg/day for one week/four weeks and Group D 20 mg every alternate day for 16 weeks. Patients were further followed for eight weeks to see any relapse. Side-effects were also recorded.

RESULTS: 

Though the daily high dose treatment Group A performed better initially at eight weeks, at the end of therapy at 16 weeks results were comparable in Group A , B and D. Patients with severe acne did better in Group A than in Group B, C and D. Patients with mild acne had almost similar results in all the groups while patients with moderate acne did better in Group A, B and D. Frequency and severity of treatment-related side-effects were significantly higher in treatment Group A as compared to Group B, C and D.

CONCLUSION: 

We conclude that for severe acne either conventional high doses of isotretinoin may be used or we can give conventional high dose for initial eight weeks and later maintain on low doses. Use of isotretinoin should be considered in mild to moderate acne also, in low doses; 20 mg, alternate day seems to be an effective and safe treatment option in such cases.

PMID: 22016276

Clin Drug Investig. 2011;31(8):599-604. doi: 10.2165/11539570-000000000-00000.

Combination of low-dose isotretinoin and pulsed oral azithromycin in the management of moderate to severe acne: a preliminary open-label, prospective, non-comparative, single-centre study.

De D, Kanwar AJ.

Source

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Abstract

BACKGROUND: 

The conventionally used dose of isotretinoin in acne causes significant dose-related adverse effects. Low-dose isotretinoin has been used successfully in mild to moderate papulopustular acne. Although isotretinoin acts against all mechanisms of acne formation, it has no significant direct antimicrobial effect.

OBJECTIVE: 

To test whether the addition of an antibacterial enables use of isotretinoin in low doses even in moderate to severe acne.

METHODS: 

This was a preliminary open-label, prospective, non-comparative, single-centre study carried out in a tertiary-care referral hospital. Seventy patients with grade 3 and 4 acne according to the US FDA global score were included in the study between October 2005 and December 2007. These patients were treated with a combination of low-dose isotretinoin (0.3 mg/kg/day) and pulsed oral azithromycin (500 mg/day over three consecutive days every 2 weeks). Response to treatment was assessed at monthly intervals and was recorded as a percentage decrease in overall severity of disease. Treatment was continued to complete clearance of lesions or to 16 weeks, whichever came later.

RESULTS: 

Sixty-two (93.9%) of 66 eligible patients had complete clearance of disease activity after a mean treatment duration of 21 weeks. The mean total cumulative dose of isotretinoin was 49.6 mg/kg. Seven (11.3%) patients had a relapse of disease during the post-treatment follow-up period. Fifty-three adverse effects were observed. Three patients had initial aggravation of disease that was managed with prednisolone and disappeared with continuation of treatment.

CONCLUSION: 

A combination of low-dose isotretinoin and oral azithromycin pulse is effective in severe acne and has a reasonably acceptable adverse-effect profile and low post-treatment relapse rates.

PMID: 21591819

Arthritis Care Res (Hoboken). 2012 Mar;64(3):389-96. doi: 10.1002/acr.20692.

Independent association of serum retinol and β-carotene levels with hyperuricemia: A national population study.

Choi WJ, Ford ES, Curhan G, Rankin JI, Choi HK.

Source

Arthritis Research Centre of Canada, Vancouver, British Columbia, Canada.

Abstract

OBJECTIVE: 

Uses of synthetic vitamin A derivatives (e.g., isotretinoin used for severe acne) and high doses of preformed vitamin A have been implicated in the pathogenesis of hyperuricemia and gout, whereas a trial reported that β-carotene may lower serum uric acid (UA) levels. We evaluated the potential population impact of these factors on serum UA in a nationally representative sample of US adults.

METHODS: 

Using data from 14,349 participants ages ≥20 years in the Third National Health and Nutrition Examination Survey (1988-1994), we examined the relationship between serum retinol, β-carotene, and UA levels using weighted linear regression. Additionally, we examined the relationship with hyperuricemia using weighted logistic regression.

RESULTS: 

Serum UA levels increased linearly with increasing serum retinol levels, whereas serum UA levels decreased with increasing serum β-carotene levels. After adjusting for age, sex, dietary factors, and other potential confounders, the serum UA level differences from the bottom (referent) to the top quintiles of serum retinol levels were 0, 0.16, 0.32, 0.43, and 0.71 mg/dl (P for trend <0.001), and for β-carotene were 0, -0.15, -0.29, -0.27, and -0.40 mg/dl (P for trend <0.001), respectively. Similarly, the multivariate odds ratios of hyperuricemia from the bottom (referent) to top quintiles of serum retinol levels were 1.00, 1.30, 1.83, 2.09, and 3.22 (P for trend <0.001) and for β-carotene were 1.00, 0.85, 0.68, 0.73, and 0.54 (P for trend <0.001), respectively. The graded associations persisted across subgroups according to cross-classification by both serum retinol and β-carotene levels.

CONCLUSION: 

These nationally representative data raise concerns that vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas β-carotene intake may be beneficial against hyperuricemia. The use of β-carotene as a novel preventive treatment for gout deserves further investigation.

Copyright © 2012 by the American College of Rheumatology.

PMID: 22076806

Dermatology. 2003;206(1):37-53.

Update and future of systemic acne treatment.

Zouboulis CC, Piquero-Martin J.

Source

Department of Dermatology, University Medical Center Benjamin Franklin, The Free University of Berlin, Berlin, Germany. zouboulis@medizin.fu-berlin.de

Abstract

Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8-12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5alpha-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors.

Copyright 2003 S. Karger AG, Basel

PMID: 12566804

Health Technol Assess. 2005 Jan;9(1):iii-212.

Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.

Ozolins M, Eady EA, Avery A, Cunliffe WJ, O'Neill C, Simpson NB, Williams HC.

Source

Department of Dermatology, University of Nottingham, UK.

Abstract

OBJECTIVES: 

To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains.

DESIGN: 

This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks.

SETTING: 

Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England.

PARTICIPANTS: 

Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face.

INTERVENTIONS: 

Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group).

MAIN OUTCOME MEASURES: 

The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots).

RESULTS: 

The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study.

CONCLUSIONS: 

The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).

PMID: 15588555

Br J Dermatol. 1996 Jan;134(1):107-13.

The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin-resistant propionibacteria.

Eady EA, Bojar RA, Jones CE, Cove JH, Holland KT, Cunliffe WJ.

Source

Department of Microbiology, University of Leeds, U.K.

Abstract

Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of erythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P < 0.001, Wilcoxon's matched pairs) and also significantly reduced the number of erythromycin-resistant propionibacteria (P < 0.05). In contrast, erythromycin alone reduced the total propionibacterial count by < 1.5 log10 c.f.u./cm2 after 6 weeks (P < 0.05) and did not affect the number of erythromycin-resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P < 0.01, Mann-Whitney) and 12 weeks (P < 0.05) than erythromycin alone, although, after 12 weeks, the anti-propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin-resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried > 10(3) c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo anti-propionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.

PMID: 8745894

Skin Therapy Lett. 2010 Mar;15(3):1-2, 5.

Does diet really affect acne?

Ferdowsian HR, Levin S.

Source

Physicians Committee for Responsible Medicine, Washington, DC, USA.

Abstract

Acne vulgaris has anecdotally been attributed to diet by individuals affected by this skin condition. In a 2009 systematic literature review of 21 observational studies and 6 clinical trials, the association between acne and diet was evaluated. Observational studies, including 2 large controlled prospective trials, reported that cow's milk intake increased acne prevalence and severity. Furthermore, prospective studies, including randomized controlled trials, demonstrated a positive association between a high-glycemic-load diet, hormonal mediators, and acne risk. Based on these findings, there exists convincing data supporting the role of dairy products and high-glycemic-index foods in influencing hormonal and inflammatory factors, which can increase acne prevalence and severity. Studies have been inconclusive regarding the association between acne and other foods.

PMID: 20361171

Mol Nutr Food Res. 2008 Jun;52(6):718-26.

A pilot study to determine the short-term effects of a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial.

Smith R, Mann N, Mäkeläinen H, Roper J, Braue A, Varigos G.

Source

School of Applied Sciences, RMIT University, Melbourne, Australia. robyn.smith@rmit.edu.au

Abstract

Observational evidence suggests that dietary glycemic load may be one environmental factor contributing to the variation in acne prevalence worldwide. To investigate the effect of a low glycemic load (LGL) diet on endocrine aspects of acne vulgaris, 12 male acne sufferers (17.0 +/- 0.4 years) completed a parallel, controlled feeding trial involving a 7-day admission to a housing facility. Subjects consumed either an LGL diet (n = 7; 25% energy from protein and 45% from carbohydrates) or a high glycemic load (HGL) diet (n = 5; 15% energy from protein, 55% energy from carbohydrate). Study outcomes included changes in the homeostasis model assessment of insulin resistance (HOMA-IR), sex hormone binding globulin (SHBG), free androgen index (FAI), insulin-like growth factor-I (IGF-I), and its binding proteins (IGFBP-I and IGFBP-3). Changes in HOMA-IR were significantly different between groups at day 7 (-0.57 for LGL vs. 0.14 for HGL, p = 0.03). SHBG levels decreased significantly from baseline in the HGL group (p = 0.03), while IGFBP-I and IGFBP-3 significantly increased (p = 0.03 and 0.03, respectively) in the LGL group. These results suggest that increases in dietary glycemic load may augment the biological activity of sex hormones and IGF-I, suggesting that these diets may aggravate potential factors involved in acne development.

PMID: 18496812

Am J Clin Nutr. 2007 Jul;86(1):107-15.

A low-glycemic-load diet improves symptoms in acne vulgaris patients: a randomized controlled trial.

Smith RN, Mann NJ, Braue A, Mäkeläinen H, Varigos GA.

Source

School of Applied Sciences, RMIT University, Melbourne, Australia. robyn.smith@rmit.edu.au

Abstract

BACKGROUND: 

Although the pathogenesis of acne is currently unknown, recent epidemiologic studies of non-Westernized populations suggest that dietary factors, including the glycemic load, may be involved.

OBJECTIVE: 

The objective was to determine whether a low-glycemic-load diet improves acne lesion counts in young males.

DESIGN: 

Forty-three male acne patients aged 15-25 y were recruited for a 12-wk, parallel design, dietary intervention incorporating investigator-blinded dermatology assessments. The experimental treatment was a low-glycemic-load diet composed of 25% energy from protein and 45% from low-glycemic-index carbohydrates. In contrast, the control situation emphasized carbohydrate-dense foods without reference to the glycemic index. Acne lesion counts and severity were assessed during monthly visits, and insulin sensitivity (using the homeostasis model assessment) was measured at baseline and 12 wk.

RESULTS: 

At 12 wk, mean (+/-SEM) total lesion counts had decreased more (P=0.03) in the low-glycemic-load group (-23.5 +/- 3.9) than in the control group (-12.0 +/- 3.5). The experimental diet also resulted in a greater reduction in weight (-2.9 +/- 0.8 compared with 0.5 +/- 0.3 kg; P<0.001) and body mass index (in kg/m(2); -0.92 +/- 0.25 compared with 0.01 +/- 0.11; P=0.001) and a greater improvement in insulin sensitivity (-0.22 +/- 0.12 compared with 0.47 +/- 0.31; P=0.026) than did the control diet.

CONCLUSION: 

The improvement in acne and insulin sensitivity after a low-glycemic-load diet suggests that nutrition-related lifestyle factors may play a role in the pathogenesis of acne. However, further studies are needed to isolate the independent effects of weight loss and dietary intervention and to further elucidate the underlying pathophysiologic mechanisms.

PMID: 17616769

Bosn J Basic Med Sci. 2010 Aug;10(3):260-4.

Outcomes of 3% green tea emulsion on skin sebum production in male volunteers.

Mahmood T, Akhtar N, Khan BA, Khan HM, Saeed T.

Source

Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.

Abstract

This study was aimed to depict potential effects of stable formulation (water in oil emulsion), containing 3% green tea (Camellia sinensis L) extract on skin sebum production in healthy human volunteers. For this purpose formulation was designed using 3% ethanolic green tea extract and Abil®EM90 was used as an emulsifier. Formulation was applied to the cheeks of healthy human volunteers (n=10) for a period of 8 weeks. Measurements for skin sebum production were considered using Sebumeter MPA 5. Results were compiled and any effect produced by the formulation was justified statistically. It was observable that statistically significant (p < 0.5%) results were found for skin sebum production after long term application of the formulation. 3% formulation of green tea extract was ideal in all aspects and can be experienced in skin disorders like acne to further investigate its effects in unhealthy volunteers.

PMID: 20846135

I'm been struck by the comparison between autism spectrum and ADHD. It looks like diet may be helpful in either case. 

Pediatrics. 2012 Jan 9. [Epub ahead of print]

The Diet Factor in Attention-Deficit/Hyperactivity Disorder.

Millichap JG, Yee MM.

Source

Division of Neurology, Children's Memorial Hospital, and Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois.

Abstract

This article is intended to provide a comprehensive overview of the role of dietary methods for treatment of children with attention-deficit/hyperactivity disorder (ADHD) when pharmacotherapy has proven unsatisfactory or unacceptable. Results of recent research and controlled studies, based on a PubMed search, are emphasized and compared with earlier reports. The recent increase of interest in this form of therapy for ADHD, and especially in the use of omega supplements, significance of iron deficiency, and the avoidance of the "Western pattern" diet, make the discussion timely.Diets to reduce symptoms associated with ADHD include sugar-restricted, additive/preservative-free, oligoantigenic/elimination, and fatty acid supplements. Omega-3 supplement is the latest dietary treatment with positive reports of efficacy, and interest in the additive-free diet of the 1970s is occasionally revived. A provocative report draws attention to the ADHD-associated "Western-style" diet, high in fat and refined sugars, and the ADHD-free "healthy" diet, containing fiber, folate, and omega-3 fatty acids.The literature on diets and ADHD, listed by PubMed, is reviewed with emphasis on recent controlled studies. Recommendations for the use of diets are based on current opinion of published reports and our practice experience. Indications for dietary therapy include medication failure, parental or patient preference, iron deficiency, and, when appropriate, change from an ADHD-linked Western diet to an ADHD-free healthy diet. Foods associated with ADHD to be avoided and those not linked with ADHD and preferred are listed.In practice, additive-free and oligoantigenic/elimination diets are time-consuming and disruptive to the household; they are indicated only in selected patients. Iron and zinc are supplemented in patients with known deficiencies; they may also enhance the effectiveness of stimulant therapy. In patients failing to respond or with parents opposed to medication, omega-3 supplements may warrant a trial. A greater attention to the education of parents and children in a healthy dietary pattern, omitting items shown to predispose to ADHD, is perhaps the most promising and practical complementary or alternative treatment of ADHD.

PMID: 22232312 Ned Tijdschr Geneeskd. 2002 Dec 28;146(52):2543-7. Related Articles, Links 

Comment in: 

Ned Tijdschr Geneeskd. 2003 Mar 29;147(13):630-1; author reply 631. 

Ned Tijdschr Geneeskd. 2003 Mar 29;147(13):630; author reply 631. 

[Favourable effect of a standard elimination diet on the behavior of young children with attention deficit hyperactivity disorder (ADHD): a pilot study]

[Article in Dutch]

Pelsser LM, Buitelaar JK.

Onderzoekscentrum voor Hyperactiviteit en ADHD, Vlokhovenseweg 11, 5625 WT Eindhoven. lmjpelsser@worldmail.nl

OBJECTIVE: To determine whether a standard elimination diet can decrease the ADHD-symptoms in a heterogeneous group of young children with ADHD. DESIGN: Open, descriptive. METHOD: 40 children, 36 boys and 4 girls, aged 3-7 (average 4.8 years), who met the DSM-IV-criteria for ADHD, followed their usual diet for two weeks and thereafter for two weeks an elimination diet, based on the few foods diet (rice, turkey, pear and lettuce). The behaviour of the child was evaluated at study entry, after the baseline period and at the end of the diet. Parents completed the 10-item Conners list, the ADHD Rating Scale and a physical complaints list. The teachers completed the 10-item Conners list and the ADHD Rating Scale twice, at the beginning and at the end of the diet. RESULTS: According to the parent-ratings, 25 children (62%) showed an improvement in behaviour of at least 50% on both the Conners list and the ADHD Rating Scale at the end of the elimination diet. Nine children (23%) withdrew from the study because the parents were unable to stick to the diet or because the child fell ill. Among the 15 children with both parent and teacher ratings, 10 responded both at home and in school. CONCLUSION: In young children with ADHD an elimination diet can lead to a statistically significant decrease in symptoms.

PMID: 12532668 [PubMed - indexed for MEDLINE] 

J Dermatol. 2004 Jun;31(6):448-54. Related Articles, Links 

Psychological disturbances in Indian children with atopic eczema.

Sarkar R, Raj L, Kaur H, Basu S, Kanwar AJ, Jain RK.

Department of Dermatology & Venereology, Government Medical College and Hospital, Sector-32, Chandigarh-160031, India.

Although the link between atopic dermatitis (AD) and emotional disturbance is well known, there have been only a few studies assessing the extent of these disturbances in affected children and the problems experienced by their parents. Furthermore, these studies are mostly from western countries, where atopic dermatitis is seen in a more severe form than in India. The purpose of this study was to determine whether there is an excess of psychological disorders in Indian children with AD as compared to healthy controls and whether their mothers showed higher levels of emotional or mental distress than a comparison group. Twenty-two children, aged 3-9 years, with atopic dermatitis, twenty age and sex matched controls, and their mothers were selected for the study. The personalities of the mothers were assessed from a standard and valid questionnaire, the Hindi adaptation of Personality Trait Inventory, which explored nine areas of the maternal personality and mental distress as well as negative traits of some of these. The two groups were compared using the Chi-square test. To assess the psychopathology of the children, the mothers were made to answer parts of a valid, well-developed questionnaire, the Childhood Psychopathology Measurement Schedule, which enabled the assessment of the following factors: low intelligence with behaviour disorders, conduct disorders, anxiety, and depression. The means of each factor in both the groups were compared using the Students' t-test. Out of all the maternal personality traits, an increased number of mothers of affected children, 13 (59%) were found to be submissive as compared to the mothers of the controls i.e. 2 (10%), which was statistically significant (p<0.01). The children with AD had a higher frequency of low intelligence with behaviour disorders (5.9+/-2.9) as compared to controls and also of conduct disorders (2.1+/-1.4), which were both statistically significant (p<0.01). The results of this pilot study, although small in number, suggest that increased psychological disorders are observed in Indian children with AD as compared to controls, despite the fact that the disease is of a milder variety in this country as compared to its western counterparts. More mothers of children with AD were submissive, which could contribute to the psychological disorders and maintenance of eczema in the children. We suggest that children with AD may benefit if such psychological dimensions are considered as a part of their treatment.

PMID: 15235182 [PubMed - in process]

Body fat is not inert. It is supportive or disruptive to the body's hormonal balance. 

Vnitr Lek. 2010 Oct;56(10):1028-34.

[Adipose tissue hormones].

[Article in Czech]

Haluzík M, Trachta P, Haluzíková D.

Source

III. Interní klinika 1. lékarské fakulty UKa VFN Praha. mhalu@lf1.cuni.cz

Abstract

Adipose tissue had been traditionally considered a passive energy storage site without direct influence on energy homeostasis regulation. This view has been principally changed during early nineties by the discovery of hormonal production of adipose tissue. At present, the list of hormonally active substances of adipose tissue includes more than one hundred factors with paracrine or endocrine activity that play an important role in metabolic, food intake a inflammatory regulations and many other processes. Only minority of adipose tissue-derived hormones is produced exclusively in fat. Most of these factors is primarily put out by other tissues and organs. Adipose tissue-derived hormones are produced not only by adipocytes but also by preadipocytes, immunocompetent and endothelial cells and other cell types residing in fat. This paper summarizes current knowledge about endocrine function of adipose tissue with special respect to its changes in obesity. It also describes its possible role in the ethiopathogenesis of insulin resistance, atherosclerosis and other obesity-related pathologies.

PMID: 21105447

Int J Obes Relat Metab Disord. 1996 Apr;20(4):291-302.

The regulation of adipose tissue distribution in humans.

Björntorp P.

Source

Department of Heart and Lung Disease, Sahlgren's Hospital, University of Göteborg, Sweden.

Abstract

The regulation of adipose tissue distribution is an important problem in view of the close epidemiological and metabolic associations between centralized fat accumulation and disease. With visceral fat accumulation multiple endocrine perturbations are found, including elevated cortisol and androgens in women, as well as low growth hormone (GH) and, in men, testosterone (T) secretion. These abnormalities probably derive from a hypersensitive hypothalamo-pituitary-adrenal axis, with hyperinsulinemia related to a marked insulin resistance as a consequence. These hormonal changes exert profound effects on adipose tissue metabolism and distribution. At the adipocyte level cortisol and insulin promote lipid accumulation by expressing lipoprotein lipase activity, while T, GH and probably estrogens exert opposite effects. The consequences will most likely be more expressed in visceral than subcutaneous adipose tissues because of a higher cellularity, innervation and blood flow. Furthermore, the density of cortisol and androgen receptors seems to be higher in this than other adipose tissue regions. The endocrine perturbations found in visceral obesity with an abundance of the lipid accumulating hormones cortisol and insulin, and a relatively low secretion of the lipid mobilizing sex steroid hormones and GH would therefore be expected to be followed by visceral fat accumulation. The potential significance of local synthesis of steroid hormones in adipose tissue requires more attention. Although studies in vitro are informative when elucidating detailed mechanisms of hormonal interactions, they might not give a true picture of the regional integrated regulation of adipose tissue lipid storage and mobilization. Such information can be obtained by regional measurements of lipid mobilization by free fatty acid turnover or by microdialysis techniques, both showing lower rates of mobilization in leg than in upper body adipose tissues. More detailed information can be obtained by physiological oral administration of triglycerides, labelled with a small amount of oleic acid, followed by measurements of the regional uptake and turn-over of adipose tissue triglycerides. Such studies show lipid uptake in the order omental = retroperitoneal > subcutaneous abdominal > subcutaneous femoral adipose tissues in men, with a similar rank order for half-life of the triglyceride, indicating also a turn-over of triglycerides in that order. T amplifies these differences in men. In premenopausal women subcutaneous abdominal has a higher turnover than femoral adipose tissue. Results of studies in vitro indicate that this difference is diminished at the menopause, and restored by estrogen substitution, suggesting that the functional effects of estrogens in women are similar to those of T in men. The mechanisms are, however, probably indirect because of the apparent absence of specific estrogen and progesterone receptors in human adipose tissue. This interpretation from the studies referred to above fits well with physiological, and clinical conditions with increased visceral fat mass, where the balance between the lipid accumulating hormone couple (cortisol and insulin) and the hormones which prevent lipid accumulation and instead activate lipid mobilization pathways (sex steroid hormones and GH) is shifted to the advantage of the former. Such conditions include Cushing's syndrome, the polycystic ovary syndrome, menopause, aging, GH-deficiency, depression, smoking and excess alcohol intake. With appropriate interventions against hypercortisolemia and substitution of deficient sex steroids and GH, visceral fat mass is decreasing. Based on this evidence from physiological, clinical, interventional observations and detailed studies of mechanisms at cellular and molecular levels it is suggested that the combined endocrine abnormalities in the syndrome of visceral obesity direct storage fat to visceral adipose depots. Therefore, measurements of visceral fat accumulat

PMID: 8680455

A good idea to check for dust mite exposure and vitamin D levels. 

Ann Allergy Asthma Immunol. 2010 Apr;104(4):307-13.

Season of birth and food allergy in children.

Vassallo MF, Banerji A, Rudders SA, Clark S, Mullins RJ, Camargo CA Jr.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Abstract

BACKGROUND: The prevalence of food allergy is rising, and etiologic factors remain uncertain. Evidence implicates a role for vitamin D in the development of atopic diseases. Based on seasonal patterns of UV-B exposure (and consequent vitamin D status), we hypothesized that patients with food allergy are more often born in fall or winter.

OBJECTIVE: To investigate whether season of birth is associated with food allergy.

METHODS: We performed a multicenter medical record review of all patients presenting to 3 Boston emergency departments (EDs) for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. Months of birth in patients with food allergy were compared with that of patients visiting the ED for reasons other than food allergy.

RESULTS: We studied 1002 patients with food allergy. Of younger children with food allergy (age < 5 years), but not older children or adults, 41% were born in spring or summer compared with 59% in fall or winter (P = .002). This approximately 40:60 ratio differed from birth season in children treated in the ED for non-food allergy reasons (P = .002). Children younger than 5 years born in fall or winter had a 53% higher odds of food allergy compared with controls. This finding was independent of the suspected triggering food and allergic comorbidities.

CONCLUSIONS: Food allergy is more common in Boston children born in the fall and winter seasons. We propose that these findings are mediated by seasonal differences in UV-B exposure. These results add support to the hypothesis that seasonal fluctuations in sunlight and perhaps vitamin D may be involved in the pathogenesis of food allergy.

PMID: 20408340

Pediatr Allergy Immunol. 2004 Jun;15 Suppl 16:4-5, 9-32.

Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention.

Halken S.

Department of Pediatrics, Sønderborg Hospital, Denmark.

Abstract

The development and phenotypic expression of atopic diseases depends on a complex interaction between genetic factors, environmental exposure to allergens,and non-specific adjuvant factors, such as tobacco smoke, air pollution and infections. Preventive measures may include both exposure to allergens and adjuvant risk/protective factors and pharmacological treatment. These measures may address the general population, children at risk for development of atopic disease (high-risk infants), children with early symptoms of allergic disease or children with chronic disease. The objective for this review was to evaluate possible preventive measures as regards prevention of development of allergic disease in childhood--primary prevention--and also some aspects of the effect of specific allergy treatment as regards secondary prevention in children with allergic asthma and allergic rhinoconjunctivitis. In one prospective observational study of a birth cohort of unselected infants we evaluated possible predictive/risk factors. In two prospective intervention studies including 1 yr birth cohorts of high-risk(HR) infants we investigated the effect of feeding HR infants exclusively breast milk (BM) and/or hydrolyzed cow's milk-based formula the first 4-6 months as regards: (i) the allergy preventive effect of BM/extensively hydrolysed formula (eHF) compared with ordinary cow's milk-based formula, (ii) the effect of two different eHFs, a whey (Profylac) and a casein-based (Nutramigen) formula, as regards development of cow's milk protein allergy (CMA), and (iii) a comparison of the preventive effect of eHF (Profylac/Nutramigen) with a partially hydrolyzed cow's milk-based formula (pHF) (NanHA) as regards development of CMA. None of the mothers had a restricted diet during pregnancy or lactation period. In two prospective randomized intervention studies we evaluated the preventive effect of specific allergen avoidance and specific immunotherapy (SIT) in children with allergic asthma and allergic rhinoconjunctivitis, respectively. The combination of atopic heredity and elevated cord blood IgE resulted in the best predictive discrimination as regards development of allergic disease. The optimal high-risk group was defined by either double parental atopic predisposition or single atopic predisposition, the latter combined with a cord blood IgE > or = 0.3 kU/1. 66% of unselected infants were daily exposed to tobacco smoke, which was a significant risk factor for recurrent wheezing until the age of 1.5 yr. HR infants were breastfed for a longer period and less exposed to tobacco smoke than unselected infants. Exclusively BM/eHF for at least 4 months was associated with a significantly reduced cumulative prevalence of CMA [3.6% (5/141) vs. 20%(15/75) in the control group] up to 5 yr. The effect of the two different eHFs was similar. Exclusively breastfed infants were significantly less exposed to tobacco smoke and pets, had solid foods introduced later and belonged to higher social classes. pHF was significantly (p = 0.05) less effective than eHF as regards prevention of development of CMA. A diet period of 4 months seems to be as efficient as 6 months or more as regards development of CMA. A few ongoing prospective, randomized intervention studies have produced the first indication that avoidance of indoor allergens such as house dust mite (HDM) in HR infants may reduce the incidence of severe wheeze and sensitization during the first 1-4 yr of age. Long-term follow-up is awaited. In a prospective, double-blind placebo-controlled study in children with doctors diagnosed asthma and documented HDM allergy, we found that semipermeable polyurethane mattress and pillow encasings (Allergy Control) when compared with placebo encasings resulted in a significant perennial reduction of HDM exposure and a significant reduction in the needed dose of inhaled steroids by approximately 50% (mean dose: 408 microg--227 microg/day) after 1-yr follow-up. In another randomized prospective study we investigated the possible preventive effect of SIT in children with allergic rhinoconjunctivitis and grass/birch pollen allergy as regards development of asthma. Among those without asthma significantly fewer in the SIT group developed asthma when compared with the control group (19/79 = 24% vs.32/72 = 44%) after the first 3 yr; and methacholinebronchial provocation test results improved significant in the SIT group. The results of our studies support the evidence that the risk for development of early allergic manifestations e.g. CMA and atopic dermatitis can be reduced significantly by simple dietary measures for the first4 months of life. In all infants breastfeeding should beencouraged for at least 4-6 months, and exposure to tobacco smoke should be avoided during pregnancy and early childhood. In HR infants a documented hypoallergenic formula (at present eHF) is recommended if exclusive breastfeeding is not possible for the first 4 months. In homes of HR-infants, current evidence supports measures to reduce the levels of indoor allergens. e.g. HDM and pets. In symptomatic children allergen-specific treatment may influence both the symptoms and the prognosis. Allergen avoidance can reduce the need for pharmacological treatment, SIT may have the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. and it may be possible to interfere with the natural course of allergic diseases.

PMID: 15125698

Appl Physiol Nutr Metab. 2010 Oct;35(5):718.

Vitamin D status and recommendations to improve vitamin D status in Canadian youth.

Mark S.

Health Canada, First Nations and Inuit Health Branch, 757 Hastings Street West, Vancouver, BC V6C 3E6, Canada (e-mail: sean.mark@hc-sc.gc.ca).

Abstract

Little is known regarding the vitamin D status of Canadian youth. Our objectives were (i) to describe the vitamin D status of Quebec youth using a representative sample; (ii) to examine the relative contributions of diet, physical activity, and fat mass to the variance in plasma 25-hydroxyvitamin D(25(OH)D), the best biomarker of vitamin D status; and (iii) to examine the influence of household income and food insecurity on the intakes of dietary vitamin D, calcium, and dairy foods. To describe vitamin D status, we used data from the Quebec Child and Adolescent Health and Social Survey (QCAHS), which is a cross-sectional survey representative of Quebec youth aged 9, 13, and 16 years. For the second objective, 159 youth, aged 8 to 11 years, whose parents (at least one) were obese or had the metabolic syndrome, were used for cross-sectional analysis in the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY). Fat mass was measured using dual X-ray absorptiometry (DXA), and physical activity was assessed by an accelerometer. Finally, we analyzed data from the Canadian Community Health Survey (CCHS), which collected data from 9 to 18 year olds (N = 8960), and was representative of Canadian youth. From this survey a single 24-h dietary recall, measured height and weight, sociodemographic, and food insecurity information were available. In both the QUALITY and QCAHS study, >90% of youth had suboptimal vitamin D levels (plasma 25(OH)D < 75 nmol·L-1) at the end of winter and beginning of spring. In the QCAHS study, older youth had a higher prevalence of vitamin D deficiency (25(OH)D < 27.5 nmol·L-1) (>10%) than younger youth, and girls from low-income households had lower plasma 25(OH)D concentrations. In the QUALITY study, milk consumption and physical activity had modest associations with plasma 25(OH)D, corresponding to 2.9 nmol·L-1 and 2.1 nmol·L-1 higher plasma 25(OH)D per standard deviation increase in these exposures, respectively. In the CCHS study, we found evidence that milk intake was being displaced by sweetened beverages among low-income boys and food insecure girls. We conclude that population-wide measures to increase dietary vitamin D intake should be examined in Canadian youth.

PMID: 20962929

JPEN J Parenter Enteral Nutr. 1984 Sep-Oct;8(5):556-9.

Prophylaxis and treatment of childhood rickets with parenteral cholecalciferol.

Bertino JS Jr, Reed MD, Halpin TC Jr.

Abstract

The safety and efficacy of parenteral cholecalciferol was evaluated in the treatment and prevention of childhood rickets. Children with active disease, and those at high risk for developing rickets were treated either with intravenous or intramuscular cholecalciferol in dosages of 1000 to 1500 IU daily, for periods of 28 to 450 days. All children with rickets responded with radiographic evidence of healing. No child in the prophylaxis group developed bone disease. Side effects were minimal. Parenteral cholecalciferol is a safe and effective therapy for the treatment and prevention of childhood rickets.

PMID: 6092733

Evid Rep Technol Assess (Full Rep). 2007 Aug;(158):1-235.

Effectiveness and safety of vitamin D in relation to bone health.

Cranney A, Horsley T, O'Donnell S, Weiler H, Puil L, Ooi D, Atkinson S, Ward L, Moher D, Hanley D, Fang M, Yazdi F, Garritty C, Sampson M, Barrowman N, Tsertsvadze A, Mamaladze V.

Abstract

OBJECTIVES: To review and synthesize the literature in the following areas: the association of specific circulating 25(OH)D concentrations with bone health outcomes in children, women of reproductive age, postmenopausal women and elderly men; the effect of dietary intakes (foods fortified with vitamin D and/or vitamin D supplementation) and sun exposure on serum 25(OH)D; the effect of vitamin D on bone mineral density (BMD) and fracture or fall risk; and the identification of potential harms of vitamin D above current reference intakes.

DATA SOURCES: MEDLINE(R) (1966-June Week 3 2006); Embase (2002-2006 Week 25); CINAHL (1982-June Week 4, 2006); AMED (1985 to June 2006); Biological Abstracts (1990-February 2005); and the Cochrane Central Register of Controlled Trials (2nd Quarter 2006).

REVIEW METHODS: Two independent reviewers completed a multi-level process of screening the literature to identify eligible studies (title and abstract, followed by full text review, and categorization of study design per key question). To minimize bias, study design was limited to randomized controlled trials (RCTs) wherever possible. Study criteria for question one were broadened to include observational studies due to a paucity of available RCTs, and question four was restricted to systematic reviews to limit scope. Data were abstracted in duplicate and study quality assessed. Differences in opinion were resolved through consensus or adjudication. If clinically relevant and statistically feasible, meta-analyses of RCTs on vitamin D supplementation and bone health outcomes were conducted, with exploration of heterogeneity. When meta-analysis was not feasible, a qualitative systematic review of eligible studies was conducted.

RESULTS: 167 studies met our eligibility criteria (112 RCTs, 19 prospective cohorts, 30 case-controls and six before-after studies). The largest body of evidence on vitamin D status and bone health was in older adults with a lack of studies in premenopausal women and infants, children and adolescents. The quality of RCTs was highest in the vitamin D efficacy trials for prevention of falls and/or fractures in older adults. There was fair evidence of an association between low circulating 25(OH)D concentrations and established rickets. However, the specific 25(OH)D concentrations associated with rickets is uncertain, given the lack of studies in populations with dietary calcium intakes similar to North American diets and the different methods used to determine 25(OH)D concentrations. There was inconsistent evidence of an association of circulating 25(OH)D with bone mineral content in infants, and fair evidence that serum 25(OH)D is inversely associated with serum PTH. In adolescents, there was fair evidence for an association between 25(OH)D levels and changes in BMD. There were very few studies in pregnant and lactating women, and insufficient evidence for an association between serum 25(OH)D and changes in BMD during lactation, and fair evidence of an inverse correlation with PTH. In older adults, there was fair evidence that serum 25(OH)D is inversely associated with falls, fair evidence for a positive association with BMD, and inconsistent evidence for an association with fractures. The imprecision of 25(OH)D assays may have contributed to the variable thresholds of 25(OH)D below which the risk of fractures, falls or bone loss was increased. There was good evidence that intakes from vitamin D-fortified foods (11 RCTs) consistently increased serum 25(OH)D in both young and older adults. Eight randomized trials of ultraviolet (UV)-B radiation (artificial and solar exposure) were small and heterogeneous with respect to determination of the exact UV-B dose and 25(OH)D assay but there was a positive effect on serum 25(OH)D concentrations. It was not possible to determine how 25(OH)D levels varied by ethnicity, sunscreen use or latitude. Seventy-four trials examined the effect of vitamin D(3) or D(2) on 25(OH)D concentrations. Most trials used vitamin D(3), and the majority enrolled older adults. In three trials, there was a greater response of serum 25(OH)D concentrations to vitamin D(3) compared to vitamin D(2), which may have been due to more rapid clearance of vitamin D(2) in addition to other mechanisms. Meta-analysis of 16 trials of vitamin D(3) was consistent with a dose-response effect on serum 25(OH)D when comparing daily doses of <400 IU to doses >/= 400 IU. An exploratory analysis of the heterogeneity demonstrated a significant positive association comparable to an increase of 1 - 2 nmol/L in serum 25(OH)D for every 100 additional units of vitamin D although heterogeneity remained after adjusting for dose. Vitamin D(3) in combination with calcium results in small increases in BMD compared to placebo in older adults although quantitative synthesis was limited due to variable treatment durations and BMD sites. The evidence for fracture reduction with vitamin D supplementation was inconsistent across 15 trials. The combined results of trials using vitamin D(3) (700 - 800 IU daily) with calcium (500 - 1,200 mg) was consistent with a benefit on fractures although in a subgroup analysis by setting, benefit was primarily in elderly institutionalized women (fair evidence from two trials). There was inconsistent evidence across 14 RCTs of a benefit on fall risk. However, a subgroup analysis showed a benefit of vitamin D in postmenopausal women, and in trials that used vitamin D(3) plus calcium. In addition, there was a reduction in fall risk with vitamin D when six trials that adequately ascertained falls were combined. Limitations of the fall and fracture trials included poor compliance with vitamin D supplementation, incomplete assessment of vitamin D status and large losses to follow-up. We did not find any systematic reviews that addressed the question on the level of sunlight exposure that is sufficient to maintain serum 25(OH)D concentrations but minimizes risk of melanoma and non-melanoma skin cancer. There is little evidence from existing trials that vitamin D above current reference intakes is harmful. In most trials, reports of hypercalcemia and hypercalciuria were not associated with clinically relevant events. The Women's Health Initiative study did report a small increase in kidney stones in postmenopausal women aged 50 to 79 years whose daily vitamin D(3) intake was 400 IU (the reference intake for 50 to 70 years, and below the reference intake for > 70 years) combined with 1000 mg calcium. The increase in renal stones corresponded to 5.7 events per 10,000 person-years of exposure. The women in this trial had higher calcium intakes than is seen in most post-menopausal women.

CONCLUSIONS: The results highlight the need for additional high quality studies in infants, children, premenopausal women, and diverse racial or ethnic groups. There was fair evidence from studies of an association between circulating 25(OH)D concentrations with some bone health outcomes (established rickets, PTH, falls, BMD). However, the evidence for an association was inconsistent for other outcomes (e.g., BMC in infants and fractures in adults). It was difficult to define specific thresholds of circulating 25(OH)D for optimal bone health due to the imprecision of different 25(OH)D assays. Standard reference preparations are needed so that serum 25(OH)D can be accurately and reliably measured, and validated. In most trials, the effects of vitamin D and calcium could not be separated. Vitamin D(3) (>700 IU/day) with calcium supplementation compared to placebo has a small beneficial effect on BMD, and reduces the risk of fractures and falls although benefit may be confined to specific subgroups. Vitamin D intake above current dietary reference intakes was not reported to be associated with an increased risk of adverse events. However, most trials of higher doses of vitamin D were not adequately designed to assess long-term harms.

PMID: 18088161

Allergy Asthma Proc. 2001 Jan-Feb;22(1):5-9.

Seasonal variability of non-specific bronchial responsiveness in asthmatic patients with allergy to house dust mites.

Riccioni G, Di Stefano F, De Benedictis M, Verna N, Cavallucci E, Paolini F, Di Sciascio MB, Della Vecchia R, Schiavone C, Boscolo P, Conti P, Di Gioacchino M.

Respiratory Physiopathology Center, G. D'Annunzio University, Chieti, Italy.

Abstract

The aim of the study was to assess the seasonal variability of non-specific bronchial responsiveness to methacholine in allergic asthma. One hundred sixty-five patients (83 male and 82 female) entered the study: 86 subjects (group A) with allergy exclusively to mites and 79 (group B) with concomitant allergy to pollens, e.g., "Graminae" and "Parietaria." Inclusion criteria were the absence of sensitization to other allergens, no smoking habit, withdrawal from steroids, bronchodilators, sodium cromoglycate, and antihistamines for at least four weeks before enrollment, FEV1 > 70% of the predicted value, and absence of other respiratory diseases and of upper and lower respiratory tract infections for at least one month before the methacholine challenge. None of the patients had been previously treated with specific immunotherapy. Subjects of each group (A and B) underwent methacholine challenge at first visit and were divided into four subgroups according to the period when the challenge was performed. Subgroups A1 and B1 performed the challenge in December, January, and February; subgroups A2 and B2 in March, April, and May; subgroups A3 and B3 in June, July, and August; subgroups A4 and B4 in September, October, and November. PD20 values were expressed as the natural logs of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Statistical analysis was carried out using multiple group analysis and Student's t-test. Results showed that the highest non-specific bronchial responsiveness was observed in autumn (ln PC20 = 4.54 +/- 1.51) in patients allergic to mites only (group A), and in summer (ln PC20 = 4.72 +/- 2.11) in those of group B. Multiple group analysis showed statistical significant differences between subgroups within each group (group A, p = 0.039; group B, p < 0.001). In patients allergic exclusively to house dust mites (group A), multiple comparisons and Student's t-test showed statistically significant differences between non-specific bronchial responsiveness (NSBR) assessed in autumn and those of other seasons (winter, p = 0.002; spring, p < 0.001; summer, p = 0.082). These results confirm that the level of allergen exposure may influence NSBR. Mite-allergic patients showed an increase of NSBR in autumn, possibly as a consequence of higher indoor mite concentration. However, mite- and grass-allergic patients had wider variations of NSBR, possibly reflecting changes in seasonal pollen concentration.

PMID: 11227919

I'm a fan of SLIT over SCIT (oral vs. injected) for allergy desensitization. A couple other options (honey, anyone?) touched on. 

Practitioner. 2011 May;255(1740):27-31, 2.

Dentify the culprit allergen in seasonal allergic rhinitis.

Prashantha M, Drewe E.

Source

Nottingham University Hospitals NHS Trust.

Abstract

Seasonal allergic rhinitis (SAR) is the main form of rhinitis in children whereas in adults it accounts for about a third of cases of rhinitis. It is a risk factor for the development of asthma and chronic rhinosinusitis. The most common allergic triggers are grass and tree pollens, allergy to moulds and weeds is less common. Identifying the months of the year when an individual is symptomatic will help define the culprit allergen. If there is a clear recurring seasonal history the diagnosis may be made on the strength of the history. Skin prick tests are available in specialist clinics and are a useful tool in differentiating SAR from non-allergic rhinitis and defining the culprit allergen(s). Specific IgE tests for suspected allergens can be performed if skin tests are not available. A positive specific IgE test to an allergen does not necessarily mean that clinical allergy is present, it may reflect sensitisation of the immune system. Although, in general, specific IgE tests have a high negative predictive value they are less sensitive than skin prick tests for grass pollen and moulds. Allergen avoidance is the first step in the management of any allergic rhinitis. Oral non-sedating antihistamines are recommended as first-line treatment for mild SAR, higher doses may be necessary in moderate to severe SAR. Intranasal corticosteroids should be used in moderate to severe forms of SAR and also in mild forms where treatment with antihistamines has failed. There are no major differences in terms of efficacy between different corticosteroid preparations. Long-term growth studies in children using fluticasone, mometasone and budesonide (but not beclometasone) have been reassuring.

PMID: 21714475

Allerg Immunol (Leipz). 1987;33(4):215-21.

[Allergologic-immunochemical study of tree and bush pollen. II--Study of the sensitization spectrum of patients with seasonal rhinitis in the spring].

[Article in German]

Jung K, Schlenvoigt G, Jäger L.

Source

Institut für Klinische Immunologie, Friedrich-Schiller-Universität, Jena.

Abstract

80 patients sera were investigated by means of radioallergosorbent test (RAST) and enzyme linked immunosorbent assay (ELISA). Specific IgE antibodies against ten various tree pollens were determined. There is a significant correlation between RAST and ELISA results. It was found that birch, beech, alder, hazel and oak pollens are most important as causes of springtime hay fever. 75% of patients had increased specific IgE-titres against these pollens whereas maple, poplar, elm, sallow and ash allergens more often gave negative or only weak positive test results.

PMID: 2964175

Clin Exp Allergy. 2011 Sep;41(9):1313-1323. doi: 10.1111/j.1365-2222.2011.03803.x. Epub 2011 Jul 15.

A national audit of pollen immunotherapy for children in the United Kingdom: patient selection and programme safety.

Vance GH, Goldring S, Warner JO, Cox H, Sihra B, Hughes S, Gardner J, North J, Roberts G, Proudfoot CA, Clarke A, Luyt DK, Gillies D, Fox AT.

Source

Great North Children's Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK Imperial College and St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK Imperial College and Imperial College Healthcare NHS Trust Biomedical Research Centre, London, UK Colchester Hospital University NHS Foundation Trust, Essex, UK Royal Manchester Children's Hospital, Central Manchester Foundation Trust, London, UK Royal Free Hampstead NHS Trust, London, UK City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Sandwell, UK Faculty of Medicine, University of Southampton, Southampton, UK Southampton University Hospital NHS Trust, Southampton, UK Countess of Chester Hospital Foundation Trust, Chester, UK Departments of Medicine and Paediatrics, University of Cambridge, Addenbrookes Hospital, Cambridge, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK Harrogate and District NHS Foundation Trust, Harrogate, UK MRC and Asthma UK Centre in Allergic Mechanisms of Asthma, Division of Asthma, Allergy and Lung Biology, King's College London, Guy's and St Thomas' NHS Foundation Trust, London, UK.

Abstract

Background Specific immunotherapy (SIT) is an effective treatment for grass and/or tree pollen-induced severe allergic rhinoconjunctivitis. However, there are limited detailed data on the use of immunotherapy in children in the United Kingdom. Objectives We audited NHS paediatric practice against current national guidelines to evaluate patient selection, SIT modalities and adverse events (AEs). Methods Paediatricians offering pollen SIT were identified through the British Society of Allergy and Clinical Immunology Paediatric Allergy Group (BSACI-PAG) and the database of SIT providers compiled for the Royal College of Physicians and Royal College of Pathologists 2010 joint working group. Standardized proformas were returned by 12 of 20 centres (60%), including 12 of 14 centres offering subcutaneous immunotherapy (SCIT) (85%). Results Three hundred and twenty-three children, with mean age 11 years at initiation (69% boys), had undergone 528 SIT cycles (SCIT 31%) over 10 years. Fifty-five percent of all patients had asthma. Among SCIT programmes 24.5% patients had perennial (± seasonal) asthma; 75.6% of asthmatics undertaking SCIT had treatments at BTS/SIGN step 2 or above. AEs occurred frequently (50.4% of all SIT cycles) but were mild. In sublingual immunotherapy (SLIT) treatment, local intraoral immediate reactions were most common (44.9% SLIT cycles), as compared with delayed reactions around the injection site in SCIT (28.3% SCIT cycles). An asthma diagnosis had no impact on the number of cycles with AEs, or the severity reported. Few cycles (2.9%) were discontinued as a result of AE(s). Conclusions and Clinical Relevance Pollen SIT is available across England, though small numbers of children are being treated. Current national guidelines to exclude asthmatic children in SIT programmes are not being adhered to by most specialist paediatric allergy centres. SCIT and SLIT has been well tolerated. Review of patient selection criteria is needed and may allow greater use of this therapeutic option in appropriate clinical settings. Cite this as: G. H. S. Vance, S. Goldring, J. O. Warner, H. Cox, B. Sihra, S. Hughes, J. Gardner, J. North, G. Roberts, C. A. Proudfoot, A. Clarke, D. K. Luyt, D. Gillies and A. T. Fox, Clinical & Experimental Allergy, 2011 (41) 1313-1323.

© 2011 Blackwell Publishing Ltd.

PMID: 21762222

Cochrane Database Syst Rev. 2007 Jan 24;(1):CD001936.

Allergen injection immunotherapy for seasonal allergic rhinitis.

Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S.

Source

Royal Brompton Hospital, Department of Allergy and Respiratory Medicine, Imperial College School of Medicine at the National Heart and Lung Institute, London, UK, SW3 6LY. m.calderon@imperial.ac.uk

Abstract

BACKGROUND: 

Allergic rhinitis is the most common of the allergic diseases. Despite improved understanding of the pathophysiology of allergic rhinitis and advances in its pharmacological treatment, its prevalence has increased worldwide. For patients whose symptoms remain uncontrolled despite medical treatment, allergen injection immunotherapy is advised. An allergen-based treatment may reduce symptoms, the need for medication and modify the natural course of this disease.

OBJECTIVES: 

To evaluate the efficacy and safety of subcutaneous specific allergen immunotherapy, compared with placebo, for reducing symptoms and medication requirements in seasonal allergic rhinitis patients.

SEARCH STRATEGY: 

We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2006), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), Pre-MEDLINE, KOREAMED, INDMED, LILACS, PAKMEDINET, Scisearch, mRCT and the National Research Register. The date of the last search was February 2006.

SELECTION CRITERIA: 

All studies identified by the searches were assessed to identify randomised controlled trials involving participants with symptoms of seasonal allergic rhinitis and proven allergen sensitivity, treated with subcutaneous allergen specific immunotherapy or corresponding placebo.

DATA COLLECTION AND ANALYSIS: 

Two independent authors identified all studies reporting double-blind, placebo controlled randomised trials of specific immunotherapy in patients with seasonal allergic rhinitis due to tree, grass or weed pollens. Two authors independently performed quality assessment of studies. Data from identified studies were abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.2.8. Analysis was performed using the Standardised Mean Difference (SMD) method and a random-effects model; P values < 0.05 were considered statistically significant. The primary outcome measures were symptom scores, medication use, quality of life and adverse events.

MAIN RESULTS: 

We retrieved 1111 publications of which 51 satisfied our inclusion criteria. In total there were 2871 participants (1645 active, 1226 placebo), each receiving on average 18 injections. Duration of immunotherapy varied from three days to three years. Symptom score data from 15 trials were suitable for meta-analysis and showed an overall reduction in the immunotherapy group (SMD -0.73 (95% CI -0.97 to -0.50, P < 0.00001)). Medication score data from 13 trials showed an overall reduction in the immunotherapy group (SMD of -0.57 (95% CI -0.82 to -0.33, p<0.00001)). Clinical interpretation of the effect size is difficult. Adrenaline was given in 0.13% (19 of 14085 injections) of those on active treatment and in 0.01% (1 of 8278 injections) of the placebo group for treatment of adverse events. There were no fatalities.

AUTHORS' CONCLUSIONS: 

This review has shown that specific allergen injection immunotherapy in suitably selected patients with seasonal allergic rhinitis results in a significant reduction in symptom scores and medication use. Injection immunotherapy has a known and relatively low risk of severe adverse events. We found no long-term consequences from adverse events.

Comment in

Otolaryngol Head Neck Surg. 2007 Apr;136(4):511-4. 

PMID: 17253469

Phytomedicine. 2001 Jan;8(1):8-15.

Effects of an oriental herbal medicine, "Saiboku-to", and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats.

Ikarashi Y, Yuzurihara M, Sakakibara I, Takahashi A, Ishimaru H, Maruyama Y.

Source

Department of Neuropsychopharmacology (Tsumura), Gunma University School of Medicine, Maebashi, Japan. ikarishi@med.gumna-u.ac.jp

Abstract

Effects of a traditional oriental herbal medicine, "Saiboku-to" and its constituent herbs on Compound 48/80-induced histamine release from peritoneal mast cells in rats were investigated. Saiboku-to inhibited Compound 48/80-induced degranulation of and histamine release from the mast cells, suggesting that Saiboku-to not only possesses anti-histamine release effect from mast cells, but also contains active herbs with this effect. Significant inhibitions were found in 4 of 10 constituent herbs of Saiboku-to: Magnoliae Cortex, Perillae Herba, Bupleuri Radix and Hoelen. In the dose-response curves of the four herbs, the logarithmic linearity was observed for each herb, and 50% inhibitory concentration, the IC50 values, were calculated to be 56.8 microg/ml for Magnoliae Cortex, 175.8 microl/ml for Perillae Herba, 356.6 microg/ml for Bupleuri Radix, and 595.8 microg/ml for Hoelen. One mg/ml of Saiboku-to showing 75% inhibition of Compound 48/80-induced histamine release level from mast cells contains 88.5 microg of Magnoliae Cortex (it was estimated from the dose-response curve that this dose inhibits 62.68% of the Compound 48/80-induced histamine release level), 58.8 microg of Perillae Herba (21% inhibition), 205.9 microg of Bupleuri Radix (35.24% inhibition), and 147.1 microg of Hoelen (11.15% inhibition). From these results, it is suggested that the anti-histamine release effect of Saiboku-to, which contains 10 herbs, may be due mainly to the effect of Magnoliae Cortex and the synergism of the 3 other herbs.

PMID: 11292243

Photochem Photobiol. 2011 Mar-Apr;87(2):474-7. doi: 10.1111/j.1751-1097.2010.00882.x. Epub 2011 Jan 24.

Intranasal phototherapy is more effective than fexofenadine hydrochloride in the treatment of seasonal allergic rhinitis: results of a pilot study.

Garaczi E, Boros-Gyevi M, Bella Z, Csoma Z, Kemény L, Koreck A.

Source

Department of Dermatology and Allergology, University of Szeged, Szeged, Hungary. egaraczi@yahoo.com

Abstract

We recently showed that intranasal phototherapy represents an efficient therapeutic modality for the treatment of patients with seasonal allergic rhinitis (SAR). The aim of this pilot study was to compare the efficacy of intranasal phototherapy with that of the new generation antihistamine fexofenadine HCl in SAR. A randomized open study was conducted in patients with a history of moderate-to-severe ragweed-induced SAR. Thirty-one patients were randomly assigned to receive either intranasal irradiation three times a week for 2 weeks, or 180 mg fexofenadine HCl per day for 2 weeks. Each patient kept a diary of symptoms for nasal obstruction, nasal itching, rhinorrhea, sneezing and palate itching. Total nasal score (TNS), a sum of scores for nasal symptoms, was also calculated. In the rhinophototherapy group the individual scores significantly decreased compared with baseline for all of the parameters. In the fexofenadine HCl group none of the scores improved significantly at the end of the treatment except sneezing. TNS was significantly decreased in the rhinophototherapy group, but no significant change was observed in the fexofenadine HCl group after 2 weeks of treatment. In conclusion, we found that intranasal phototherapy is more efficient than fexofenadine HCl in reducing clinical symptoms for SAR.

© 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

PMID: 21366599

Int Arch Allergy Immunol. 2011;155(2):160-6. Epub 2010 Dec 23.

Birch pollen honey for birch pollen allergy--a randomized controlled pilot study.

Saarinen K, Jantunen J, Haahtela T.

Source

South Karelia Allergy and Environment Institute, Lappeenranta, Finland. all.env@inst.inet.fi

Abstract

BACKGROUND: 

Only a few randomized controlled trials have been carried out to evaluate various complementary treatments for allergic disorders. This study assessed the effects of the preseasonal use of birch pollen honey (BPH; birch pollen added to honey) or regular honey (RH) on symptoms and medication during birch pollen season.

METHODS: 

Forty-four patients (59% female, mean age 33 years) with physician-diagnosed birch pollen allergy consumed either BPH or RH daily in incremental amounts from November 2008 to March 2009. Seventeen patients (53% female, mean age 36 years) on their usual allergy medication served as the control group. From April to May, patients recorded daily rhinoconjunctival and other symptoms and their use of medication. Fifty patients completed the study.

RESULTS: 

During birch pollen season in 2009, BPH patients reported a 60% lower total symptom score (p < 0.01), twice as many asymptomatic days (p < 0.01), and 70% fewer days with severe symptoms (p < 0.001), and they used 50% less antihistamines (p < 0.001) compared to the control group. The differences between the BPH and RH groups were not significant. However, the BPH patients used less antihistamines than did the RH patients (p < 0.05).

CONCLUSIONS: 

Patients who preseasonally used BPH had significantly better control of their symptoms than did those on conventional medication only, and they had marginally better control compared to those on RH. The results should be regarded as preliminary, but they indicate that BPH could serve as a complementary therapy for birch pollen allergy.

Copyright © 2010 S. Karger AG, Basel.

PMID: 21196761

Biosci Biotechnol Biochem. 2003 May;67(5):1126-9.

Effect of the flavonoid components obtained from Scutellaria radix on the histamine, immunoglobulin E and lipid peroxidation of spleen lymphocytes of Sprague-Dawley rats.

Lim BO, Choue RW, Lee HY, Seong NS, Kim JD.

Source

Graduate School of East-West Medical Science, Department of Medical Nutrition, Kyung Hee University, 1 Hoeki-Dong, Dongdaemoon-Ku, Seoul 130-701, Korea. beongou@khu.ac.kr

Abstract

The effect on the IgE content induced by concanavalin A in spleen lymphocytes of the presence wogonin, ganhuangenin, wogonoside and 3,5,7,2',6'-pentahydroxyl flavanone was investigated. These flavonoid components markedly inhibited the histamine released from cells stimulated with the calcium ionophore, A23187. However, the magnitude of the inhibitory effect on the degree of lipid peroxidation by ConA of these components was in order of PHF>GHG>WG>WGS. Interestingly, WG, GHG and WGS, with a methoxyl group in the A and B rings, strongly inhibited histamine and IgE production, whereas PHF without a methoxyl group was much stronger than that for lipid peroxidation. We suggest that WG, GHG and WGS might block the pathway for the release of histamine, and that the IgE level in spleen lymphocytes is responsible for the lipid peroxidation.

PMID: 12834292

J Environ Biol. 2007 Apr;28(2):271-4.

Effect of natural preservatives on the growth of histamine producing bacteria.

Paramasivam S, Thangaradjou T, Kannan L.

Source

Centre of Advanced Study in Marine Biology, Annamalai University, Parangipettai 608 502, India.

Abstract

Present study deals with the hampering of the growth of histamine producing bacteria (HPB), by using NaCl and spices which are easily available and cheaper cost wise. For this experiment, four strains of HPB viz. Vibrio parahaemolyticus, Bacillus cereus, Pseudomonas aeruginosa and Proteus mirabilis were tested against 1 to 10% concentrations of NaCl and 1 to 5% concentrations of natural preservatives (turmeric, ginger and garlic) in a basal medium. HPB showed different growth rates at different concentrations of NaCl and natural preservatives. V. parahaemolyticus, B. cereus and Ps. aeruginosa showed no growth at 10% concentration. When the HPB growth was tested with garlic, turmeric and ginger extracts, growth of all the bacteria was inhibited by garlic and turmeric extracts at 5% concentration. In ginger, V. parahaemolyticus, B. cereus and P. mirabilis were totally inhibited at 5% concentration. But Ps. aeruginosa showed very less growth at this concentration.

PMID: 17915763

What is missing in any discussion of homeopathics is what to do when modern medical treatment is unavailable. Homeopathic arsenic seems to help when nothing else is available. The cost would be negligible, but the improvement to human quality of life might be great. No, it doesn't replace a full hospital's support, but no one is offering that to these patients. And yes, I'd love to see a full hospital available to them, but I'll settle for arsenic-free water first. 

Zhong Xi Yi Jie He Xue Bao. 2011 Jun;9(6):596-604.

An initial report on the efficacy of a millesimal potency Arsenicum Album LM 0/3 in ameliorating arsenic toxicity in humans living in a high-risk arsenic village.

Khuda-Bukhsh AR, Banerjee A, Biswas SJ, Karmakar SR, Banerjee P, Pathak S, Guha B, Haque S, Das D, De A, Das D, Boujedaini N.

Source

Department of Zoology, Laboratory of Cytogenetics and Molecular Biology, University of Kalyani, Kalyani 741235, India. prof_arkb@yahoo.co.in

Abstract

BACKGROUND: Millions of people are at risk of groundwater arsenic contamination, and there is no known remedy that can effectively remove the symptoms of prolonged arsenic poisoning. A potentized homeopathic drug, Arsenicum Album LM 0/3 (Ars Alb LM 0/3), is claimed in homeopathic literature to have the ability to treat symptoms similar to that of arsenic poisoning. OBJECTIVE: This study examines whether Ars Alb LM 0/3 could provide some degree of amelioration for the victims living in an arsenic-affected village where no arsenic-free drinking water is available. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was carried out on volunteers living in an arsenic-affected village where no arsenic-free drinking water is available. Twenty-eight volunteers from the village of Dasdiya, in Haringhata block under Nadia District, West Bengal, India, an arsenic-contaminated village where wells contain 55 to 95 μg/L arsenic, were selected to undertake a double-blind and placebo-controlled trial. The subjects provided samples of blood and urine before and after 2 months of taking either "verum" or "placebo". Another 18 subjects living in an arsenic-free village, served as the negative controls. MAIN OUTCOME MEASURES: Samples of blood and urine from the subjects were assayed for arsenic content, according to various toxicity biomarkers and pathophysiological parameters. Results: Out of the original 28 subjects, only 14 subjects provided samples while the other 14 dropped out. There were elevated levels of arsenic in the blood and urine, alkaline and acid phosphatases, lipid peroxidation, and glutathione activities and increased blood glucose, triacylglycerol, cholesterol, and low-density lipoprotein cholesterol contents, whereas there were decreased levels of aspartate and alanine aminotransferases, gamma glutamyl transferase, glucose-6-phosphate dehydrogenase contents, high-density lipoprotein cholesterol and packed cell volume in the subjects. After 2 months of homeopathic remedy administration, the verum-fed subjects showed positive modulations within these parameters with slight lowering of matrix metalloproteinase activity as compared with the placebo group. Conclusion: Ars Alb LM 0/3 shows potential for use in high-risk arsenic villages as an interim treatment for amelioration of arsenic toxicity until more extensive medical treatment and facilities can be provided to the numerous victims of arsenic poisoning.

PMID: 21669162

Sci Total Environ. 2007 Oct 1;384(1-3):141-50. Epub 2007 Jul 12.

Homeopathic remedy for arsenic toxicity?: Evidence-based findings from a randomized placebo-controlled double blind human trial.

Belon P, Banerjee A, Karmakar SR, Biswas SJ, Choudhury SC, Banerjee P, Das JK, Pathak S, Guha B, Paul S, Bhattacharjee N, Khuda-Bukhsh AR.

Source

Boiron Lab, 20 rue de la Libèration, Sainte-Foy-Lés-Lyon, France.

Abstract

Millions of people are at risk of groundwater arsenic contamination, but supply of arsenic-free drinking water is grossly inadequate. The present study was intended to examine if a potentized homeopathic remedy reportedly showing ameliorating potentials in people inhabiting high-risk arsenic-contaminated areas but drinking arsenic-free water, can also ameliorate arsenic toxicity in subjects living in high-risk arsenic-contaminated areas, and drinking arsenic-contaminated water. This pilot study was conducted on 20 males and 19 females of village Dasdiya (arsenic contaminated) who initially agreed to act as volunteers; but as many as 14, mostly placebo-fed subjects, later dropped out. 18 volunteers, 14 males and 4 females, from a distant village, Padumbasan (arsenic-free), served as negative controls. In a double blind placebo-controlled study, a potentized remedy of homeopathic Arsenicum Album-30 and its placebo (Succussed Alcohol-30) were given randomly to volunteers. Arsenic contents in urine and blood and several widely accepted toxicity biomarkers and pathological parameters in blood were analyzed before and after 2 months of administration of either verum or placebo. Elevated levels of ESR, creatinine and eosinophils and increased activities of AST, ALT, LPO and GGT were recorded in arsenic exposed subjects. Decreased levels of hemoglobin, PCV, neutrophil percentages, and GSH content and low G-6-PD activity were also observed in the arsenic exposed people. The administration of "verum" appeared to make positive modulations of these parameters, suggestive of its ameliorative potentials. Most of the subjects reported better appetite and improvement in general health, thereby indicating possibility of its use in remote arsenic-contaminated areas as an interim health support measure to a large population at risk.

PMID: 17628642

BMC Complement Altern Med. 2003 Oct 22;3:7.

Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice.

Mallick P, Mallick JC, Guha B, Khuda-Bukhsh AR.

Source

Department of Zoology, University of Kalyani, Kalyani-741235, WB, India. palash_mallick@yahoo.com

Abstract

BACKGROUND: 

Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols.

METHODS: 

Mice were divided into different sets of control (both positive and negative) and treated series (As-intoxicated, As-intoxicated plus drug-fed). Alanine amino transferase (ALT) and aspartate amino transferase (AST) activities and reduced glutathione (GSH) level in liver and blood were analyzed in the different series of mice at six different fixation intervals.

RESULTS: 

Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls.

CONCLUSIONS: 

The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

PMID: 14570596

I am not a huge fan of interventions in AF like surgery and blood thinners, as I don't see the kind of results I'd like. There may be less intensive helpful interventions. 

WHAT IS THE CURRENT STATE OF THE TREATMENTS AVAILABLE?

Am J Cardiol. 2011 May 3. [Epub ahead of print]

Non-Pharmacologic Management of Atrial Fibrillation.

Brenyo AJ, Aktas MK.

SourceUniversity of Rochester Medical Center, Strong Memorial Hospital, Department of Cardiovascular Diseases, Rochester, New York.

Abstract

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice today. Contemporary medical treatment options include atrioventricular nodal blocking agents to control heart rates during AF, antiarrhythmic drugs aimed at maintaining normal sinus rhythm, and anticoagulation therapies to reduce stroke risk. Invasive treatment of AF has emerged because of the toxicities and lack of long-term efficacy of available antiarrhythmic medications along with the lack of improvement in symptoms for rate-controlled patients. The investigators review the evolution of the current catheter-delivered AF procedures, starting with surgical maze up to and including left atrial appendage occlusion devices. Individual catheter ablation targets, anatomic and electrophysiologic, are discussed, with a particular focus on the use of an incremental ablation target strategy dependent on the type of AF being treated. In conclusion, the history of invasive AF therapy provides a basic understanding of contemporary ablation strategies and a backdrop for the cutting-edge rhythm and stroke prevention therapies of today.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:21545986

J Cardiovasc Electrophysiol. 2011 Mar 15. doi: 10.1111/j.1540-8167.2011.02035.x. [Epub ahead of print]

Patients Treated with Catheter Ablation for Atrial Fibrillation Have Long-Term Rates of Death, Stroke, and Dementia Similar to Patients Without Atrial Fibrillation.

Bunch TJ, Crandall BG, Weiss JP, May HT, Bair TL, Osborn JS, Anderson JL, Muhlestein JB, Horne BD, Lappe DL, Day JD.

SourceIntermountain Heart Rhythm Specialists Department of Cardiology, Intermountain Medical Center, Murray, Utah, USA.

Abstract

Outcomes in Patients With AF. Introduction: Atrial fibrillation (AF) adversely impacts mortality, stroke, heart failure, and dementia. AF ablation eliminates AF in most patients. We evaluated the long-term impact of AF ablation on mortality, heart failure (HF), stroke, and dementia in a large system-wide patient population. Methods: A total of 4,212 consecutive patients who underwent AF ablation were compared (1:4) to 16,848 age/gender matched controls with AF (no ablation) and 16,848 age/gender matched controls without AF. Patients were enrolled from the large ongoing prospective Intermountain AF study and were followed for at least 3 years. Results: Of the 37,908 patients, mean age 65.0 ± 13 years, 5,667 (14.9%) died, 1,296 (3.4%) had a stroke, and 1,096 (2.9%) were hospitalized for HF over >3 years of follow-up. AF ablation patients were less likely to have diabetes, but were more likely to have hypertension, HF, and significant valvular heart disease. AF ablation patients had a lower risk of death and stroke in comparison to AF patients without ablation. Alzheimer's dementia occurred in 0.2% of the AF ablation patients compared to 0.9% of the AF no ablation patients and 0.5% of the no AF patients (P < 0.0001). Other forms of dementia were also reduced significantly in those treated with ablation. Compared to patients with no AF, AF ablation patients had similar long-term rates of death, dementia, and stroke. Conclusions: AF ablation patients have a significantly lower risk of death, stroke, and dementia in comparison to AF patients without ablation. AF ablation may eliminate the increased risk of death and stroke associated with AF. (J Cardiovasc Electrophysiol, Vol. pp. 1-7).

© 2011 Wiley Periodicals, Inc.

PMID:21410581

IS SLEEP APNEA CAUSING THIS PROBLEM?

Am J Cardiol. 2011 Apr 28. [Epub ahead of print]

Meta-Analysis of Obstructive Sleep Apnea as Predictor of Atrial Fibrillation Recurrence After Catheter Ablation.

Ng CY, Liu T, Shehata M, Stevens S, Chugh SS, Wang X.

SourceCedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

Abstract

The association between obstructive sleep apnea (OSA) and atrial fibrillation (AF) is strong and is now well established. However, studies on the role of OSA on AF recurrence after catheter ablation have yielded conflicting results. The aim of the present study was to investigate the role of OSA on AF recurrence after catheter-based pulmonary vein isolation. We performed a data search on the PubMed, Web of Science, and the Cochrane databases for studies published by August 2010. In addition, we manually searched the conference proceedings of the European Society of Cardiology, American College of Cardiology, and American Heart Association for related abstracts. After the initial search returned 402 reports, we identified 6 studies with a total of 3,995 patients that met our inclusion criteria. Overall, patients with OSA have a 25% greater risk of AF recurrence after catheter ablation than those without OSA (risk ratio 1.25, 95% confidence interval 1.08 to 1.45, p = 0.003). Subgroup analysis showed that OSA diagnosed using polysomnography is a strong predictor of AF recurrence (risk ratio 1.40, 95% confidence interval 1.16 to 1.68, p = 0.0004) but not when OSA was diagnosed using the Berlin questionnaire (risk ratio 1.07, 95% confidence interval 0.91 to 1.27, p = 0.39). In conclusion, patients with OSA have significantly greater AF recurrence rates after pulmonary vein isolation. In addition to other factors, a diagnosis of OSA merits special consideration when evaluating patients for catheter-based AF ablation.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID:21529734

SURGERY?

Health Technol Assess. 2008 Nov;12(34):iii-iv, xi-xiii, 1-198.

Curative catheter ablation in atrial fibrillation and typical atrial flutter: systematic review and economic evaluation.

Rodgers M, McKenna C, Palmer S, Chambers D, Van Hout S, Golder S, Pepper C, Todd D, Woolacott N.

SourceCentre for Reviews and Dissemination, University of York, UK.

Abstract

OBJECTIVES: To determine the safety, clinical effectiveness and cost-effectiveness of radio frequency catheter ablation (RCFA) for the curative treatment of atrial fibrillation (AF) and typical atrial flutter.

DATA SOURCES: For the systematic reviews of clinical studies 25 bibliographic databases and internet sources were searched in July 2006, with subsequent update searches for controlled trials conducted in April 2007. For the review of cost-effectiveness a broad range of studies was considered, including economic evaluations conducted alongside trials, modelling studies and analyses of administrative databases.

REVIEW METHODS: Systematic reviews of clinical studies and economic evaluations of catheter ablation for AF and typical atrial flutter were conducted. The quality of the included studies was assessed using standard methods. A decision model was developed to evaluate a strategy of RFCA compared with long-term antiarrhythmic drug (AAD) treatment alone in adults with paroxysmal AF. This was used to estimate the cost-effectiveness of RFCA in terms of cost per quality-adjusted life-year (QALY) under a range of assumptions. Decision uncertainty associated with this analysis was presented and used to inform future research priorities using the value of information analysis.

RESULTS: A total of 4858 studies were retrieved for the review of clinical effectiveness. Of these, eight controlled studies and 53 case series of AF were included. Two controlled studies and 23 case series of typical atrial flutter were included. For atrial fibrillation, freedom from arrhythmia at 12 months in case series ranged from 28% to 85.3% with a weighted mean of 76%. Three RCTs suggested that RFCA is more effective than long-term AAD therapy in patients with drug-refractory paroxysmal AF. Single RCTs also suggested superiority of RFCA over electrical cardioversion followed by long-term AAD therapy and of RFCA plus AAD therapy over AAD maintenance therapy alone in drug-refractory patients. The available RCTs provided insufficient evidence to determine the effectiveness of RFCA beyond 12 months or in patients with persistent or permanent AF. Adverse events and complications were generally rare. Mortality rates were low in both RCTs and case series. Cardiac tamponade and pulmonary vein stenosis were the most frequently recorded complications. For atrial flutter, freedom from arrhythmia at 12 months in case series ranged from 85% to 92% with a weighted mean of 88%. Neither of the atrial flutter RCTs reported freedom from arrhythmia at 12 months. One RCT found a statistically significant benefit favouring ablation over AADs in terms of freedom from arrhythmia at a mean follow-up of 22 months. A second RCT reported a more modest effect favouring ablation in terms of freedom from atrial flutter at follow-up in older patients (mean age 78 years) after their first episode of flutter. In the atrial flutter case series, mortality was rare and the most frequent complications were atrioventricular block and haematomas. Complications in the RCTs were similar, except for those events likely to have been caused by AAD therapy (e.g. thyroid dysfunction). The review of cost-effectiveness evidence found one relevant study, which from a UK NHS perspective had a number of important limitations. The base-case analysis in the decision model demonstrated that if the quality of life benefits of RFCA are maintained over the remaining lifetime of the patient then the cost-effectiveness of RFCA appears clear. These findings were robust over a wide range of alternative assumptions, being between 7763 and 7910 pounds per additional QALY with very little uncertainty. If the quality of life benefits of RFCA are assumed to be maintained for no more than 5 years, cost-effectiveness of RFCA is dependent on a number of factors. Estimates of cost-effectiveness that explored the influence of these factors ranged from 23,000 to 38,000 pounds per QALY.

CONCLUSIONS: RFCA is a relatively safe and efficacious procedure for the therapeutic treatment of AF and typical atrial flutter. There is some randomised evidence to suggest that RFCA is superior to AADs in patients with drug-refractory paroxysmal AF in terms of freedom from arrhythmia at 12 months. RFCA appears to be cost-effective if the observed quality of life benefits are assumed to continue over a patient's lifetime. However, there remain uncertainties around longer-term effects of the intervention and the extent to which published effectiveness findings can be generalised to 'typical' UK practice. All catheter ablation procedures for the treatment of AF or atrial flutter undertaken in the UK should be recorded prospectively and centrally and measures to increase compliance in recording RFCA procedures may be needed. This would be of particular value in establishing the long-term benefits of RFCA and the true incidence and impact of any complications. Collection of appropriate quality of life data within any such registry would also be of value to future clinical and cost-effectiveness research in this area. Any planned multicentre RCTs comparing RFCA against best medical therapy for the treatment of AF and/or atrial flutter should be conducted among 'non-pioneering' centres using the techniques and equipment typically employed in UK practice and should measure relevant outcomes.

PMID:19036232

Am Heart J. 2009 Jul;158(1):15-20.

Mortality after catheter ablation for atrial fibrillation compared with antiarrhythmic drug therapy. A meta-analysis of randomized trials.

Dagres N, Varounis C, Flevari P, Piorkowski C, Bode K, Rallidis LS, Tsougos E, Leftheriotis D, Sommer P, Hindricks G, Kremastinos DT.

SourceUniversity of Athens, Second Cardiology Department, Attikon University Hospital, Rimini 1, Haidari, Athens, Greece. nikolaosdagres@yahoo.de

Abstract

INTRODUCTION: Nonrandomized studies suggest a survival benefit for patients with atrial fibrillation (AF) undergoing catheter ablation compared with antiarrhythmic drug (AAD) therapy. Data from randomized trials are lacking. We performed a meta-analysis on mortality in randomized controlled trials comparing AF ablation with AADs.

METHODS: Pubmed, the Cochrane Central Register of Controlled Trials, and abstracts of major conferences were searched for randomized trials comparing AF catheter ablation with AADs. Eight trials with a total of 930 patients were analyzed. Trial quality was assessed by a modified Jadad scale. Follow-up was 1 year in most trials. We assessed fixed effect risk differences (RDs) with the Mantel-Haenzel method, heterogeneity with I(2) statistic, and publication bias with Begg's funnel plot and with Egger's test.

RESULTS: A total of 7 deaths were reported: 3 in the ablation and 4 in the AAD arm. There was no difference in mortality between AF ablation and AAD therapy. The RD of mortality in all trials between patients randomized to ablation and those randomized to AADs was -0.003 (95% CI -0.018 to 0.013, P = .74) without evidence for heterogeneity (I(2) = 0%, P = .907). No potential publication bias was found. There was also no difference in rates of stroke or transient ischemic attack between ablation and antiarrhythmic therapy for AF (RD = 0.004, 95% CI -0.010 to 0.018, P = .54).

CONCLUSION: This meta-analysis of randomized controlled trials showed similar survival of patients undergoing catheter ablation for AF compared with patients treated with AADs after 12 months of follow-up. There was also no difference in the rates of stroke or transient ischemic attack. These findings can be probably explained by the low-risk young populations who were included in the trials and the relatively short 12-month follow-up.

PMID:19540387

WHAT DRUGS DO I NEED?

COUMADIN VS. ASPIRIN?

Am J Cardiol. 2010 Feb 15;105(4):502-10.

Thromboembolism in atrial fibrillation.

Menke J, Lüthje L, Kastrup A, Larsen J.

SourceUniversity Hospital, Göttingen, Germany. menke-j@t-online.de

Abstract

Thromboembolism is a severe complication in atrial fibrillation. This overview presents thromboembolic disease as a single entity, ranging from stroke through mesenteric ischemia to acute limb ischemia. The PubMed, Embase, and Cochrane databases were systematically searched for the terms "atrial fibrillation" and "thromboembolism" in reports published from January 1986 to September 2009. The information of 10 evidence-based practice guideline documents and 61 further sources was systematically extracted. In atrial fibrillation, the average annual stroke risk is increased by 2.3% (lethality 30%). The annual incidence of acute mesenteric ischemia is 0.14% (lethality 70%), and that of acute limb ischemia is 0.4% (lethality 16%). In total, approximately 80% of embolism-related deaths are from stroke and 20% from other systemic thromboembolism. The ischemic symptoms generally have an acute onset but may mimic other diseases, particularly in mesenteric ischemia. Early diagnosis and treatment can limit or even prevent tissue infarction. Guideline-recommended therapy with aspirin or warfarin reduces the thromboembolic risk. Suitable patients may optimize their warfarin therapy by self-monitoring of the international normalized ratio (INR). New oral and parenteral anticoagulants with more stable pharmacokinetics are being developed. In conclusion, atrial fibrillation predisposes to thromboembolism. If ischemic stroke or systemic thromboembolism occurs, early diagnosis and treatment can improve outcomes. The thromboembolic risks are reduced by guideline-adherent antithrombotic therapy with warfarin or aspirin. Future directions may include self-monitoring of the international normalized ratio and novel anticoagulants.

Copyright 2010 Elsevier Inc. All rights reserved.

PMID:20152245

BMJ. 2001 Feb 10;322(7282):321-6. Related Articles, Links 

Erratum in: 

BMJ. 2001 Mar 10;322(7286):587.

Comment in: 

ACP J Club. 2001 Sep-Oct;135(2):60. 

BMJ. 2001 Jul 28;323(7306):233-4; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):233; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):234-5; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):234; author reply 235-6. 

BMJ. 2001 Jul 28;323(7306):235-6. 

Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation.

Taylor FC, Cohen H, Ebrahim S.

Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary, Bristol BS2 8HW. f.c.taylor@bristol.ac.uk

OBJECTIVE: To examine the benefits and risks of long term anticoagulation (warfarin) compared with antiplatelet treatment (aspirin/indobufen) [corrected] in patients with non-rheumatic atrial fibrillation. METHODS: Meta-analysis of randomised controlled trials from Cochrane library, Medline, Embase, Cinhal, and Sigle from 1966 to December 1999. Odds ratios (95% confidence intervals) calculated to estimate treatment effects. OUTCOME MEASURES: Fatal and non-fatal cardiovascular events, reductions of which were classified as benefits. Fatal and major non-fatal bleeding events classified as risks. RESULTS: No trials were found from before 1989. There were five randomised controlled trials published between 1989-99. There were no significant differences in mortality between the two treatment options (fixed effects model: odd ratio 0.74 (95% confidence interval 0.39 to 1.40) for stroke deaths; 0.86 (0.63 to 1.17) for vascular deaths). There was a borderline significant difference in non-fatal stroke in favour of anticoagulation (0.68 (0.46 to 0.99)); and 0.75 (0.50 to 1.13) after exclusion of one trial with weak methodological design. A random effects model showed no significant difference in combined fatal and non-fatal events (odds ratio 0.79 (0.61 to 1.02)). There were more major bleeding events among patients on anticoagulation than on antiplatelet treatment (odds ratio 1.45 (0.93 to 2.27)). One trial was stopped prematurely after a significant difference in favour of anticoagulation was observed. The only trial to show a significant difference in effect (favouring anticoagulation) was methodologically weaker in design than the others. CONCLUSIONS: The heterogeneity between the trials and the limited data result in considerable uncertainty about the value of long term anticoagulation compared with antiplatelet treatment. The risks of bleeding and the higher cost of anticoagulation make it an even less convincing treatment option.

Publication Types: 

Meta-Analysis

PMID: 11159653 [PubMed - indexed for MEDLINE] 

Cochrane Database Syst Rev. 2000;(2):CD001927. Related Articles, Links 

Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.

Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. benavente@uthscsa.edu .

BACKGROUND: Non-valvular atrial fibrillation (AF) is associated with an increased risk of stroke. OBJECTIVES: The objective of this review was to characterize the efficacy and safety of oral anticoagulation (OAC) with vitamin K antagonists for the primary prevention of stroke in patients with chronic AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials (June 1999), MEDLINE database, and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized controlled trials comparing the value of OAC versus control in patients with non-valvular chronic atrial fibrillation and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of four trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Of 2313 participants without prior cerebral ischemia from five trials, about half (n = 1154) were randomized to adjusted-dose OAC with an estimated mean INRs ranging between 2.0-2.6 during 1.5 years/participant average follow-up. Participant features and study quality were similar between trials. OAC was associated with large, highly statistically significant reductions in ischemic stroke (OR = 0.34, 95% CI 0.23 - 0.52), all stroke (OR = 0.39, 95% CI 0.26 - 0. 59), all disabling or fatal stroke (OR = 0.47, 95% CI 0.28 - 0.80), and the combined endpoint of all stroke, MI or vascular death (OR = 0.56, 95% CI 0.42 - 0.76). The observed rates of intracranial and extracranial hemorrhage not significantly increased by OAC therapy, but confidence intervals were wide. REVIEWER'S CONCLUSIONS: Adjusted-dose OAC (achieved INRs between 2-3) reduces stroke as well as disabling/fatal stroke for patients with nonvalvular AF, and these benefits were not substantially offset by increased bleeding among participants in randomized clinical trials. Limitations include relatively short follow-up and imprecise estimates of bleeding risks from these selected participants. For primary prevention in AF patients who have an average stroke rate of 4%/year, about 25 strokes and about 12 disabling fatal strokes would be prevented yearly for every 1000 given OAC.

Publication Types: 

Review 

Review, Academic 

PMID: 10796453 [PubMed - indexed for MEDLINE] 

Cochrane Database Syst Rev. 2000;(2):CD001925. Related Articles, Links 

Antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks.

Benavente O, Hart R, Koudstaal P, Laupacis A, McBride R.

Division of Neurology, Department of Medicine, University of Texas. Health Sciences Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7883, USA. benavente@uthscsa.edu

BACKGROUND: Atrial fibrillation (AF) carries an increased risk of stroke; antiplatelet agents are proven effective for stroke prevention in other settings. OBJECTIVES: The objective of this review was to determine the efficacy and safety of antiplatelet therapy for prevention of stroke in patients with chronic non-valvular AF. SEARCH STRATEGY: We searched the Cochrane Stroke Group Specialised Register of Trials, MEDLINE database (June 1999), and the database of the Antithrombotic Trialists Collaboration, as well as reference lists of relevant articles. SELECTION CRITERIA: All randomized trials comparing antiplatelet therapies to placebo in patients with non-valvular AF and no history of transient ischemic attack (TIA) or stroke. DATA COLLECTION AND ANALYSIS: Trials for inclusion were independently selected by two reviewers who also extracted each outcome and double-checked the data. The Peto method was used for combining odds ratios. All analysis were, as far as possible, "intention-to-treat". Since the published results of two trials included 3-8% of participants with prior stroke or TIA, unpublished results excluding these participants were obtained from the Atrial Fibrillation Investigators. MAIN RESULTS: Among 1680 participants without prior stroke/TIA, randomized to aspirin (N = 838) or placebo in two trials, aspirin was associated with nonsignificantly lower risks of ischemic stroke (OR = 0.71, CI 95% 0. 46 - 1.10), all stroke (OR = 0.70, CI 95% 0.45 - 1.08) all disabling/fatal stroke (OR =0.88, CI 95% 0.48 - 1.58) and the constellation of stroke, MI or vascular death (OR = 0.76, CI 95% 0. 54 - 1.05 ). Considering all randomized participants including those with prior stroke or TIA, reductions in these events by aspirin were consistently smaller and marginally statistically significant: ischemic stroke (OR = 0.77, CI 95% 0.60-1.00), all stroke (OR = 0.76, CI 95% 0.61 - 0.93), all disabling/fatal stroke (OR = 0.87, CI 95% 0.64 - 1.19) and the combined outcome (OR = 0.79, CI 95% 0.64 - 0. 99). No increase in major hemorrhage was seen, but the number of hemorrhagic events was small. REVIEWER'S CONCLUSIONS: Considering all randomized data, aspirin modestly (by about 20%) reduces stroke and major vascular events in nonvalvular AF. For primary prevention among AF patients with an average stroke rate of 4.5%/year, about 10 strokes would be prevented yearly for every 1000 given aspirin.

Publication Types: 

Review 

Review, Academic 

PMID: 10796452 [PubMed - indexed for MEDLINE] 

Cochrane Database Syst Rev. 2001;(1):CD001938. Related Articles, Links 

Anticoagulants or antiplatelet therapy for non-rheumatic atrial fibrillation and flutter.

Segal JB, McNamara RL, Miller MR, Powe NR, Goodman SN, Robinson KA, Bass EB.

Medicine, Johns Hopkins School of Medicine, 1830 E. Monument St. 8th floor, Baltimore, Maryland 21205, USA. jsegal@welch.jhu.edu

BACKGROUND: Atrial fibrillation (AF) carries a high risk of stroke and other thromboembolic events. Appropriate use of drugs to prevent thromboembolism in patients with AF involves comparing the patient's risk of stroke to the risk of hemorrhage from medication use. OBJECTIVES: To quantify risk of stroke, major hemorrhage and death from using medications that have been rigorously evaluated for prevention of thromboembolism in AF. SEARCH STRATEGY: Articles were identified through the Cochrane Collaboration's CENTRAL database and MEDLINE until December 1999. SELECTION CRITERIA: Included Randomized controlled trials of drugs to prevent thromboembolism in adults with non-postoperative AF. Excluded RCTS of patients with rheumatic valvular disease. DATA COLLECTION AND ANALYSIS: Data were abstracted by two reviewers. Odds ratios from all qualitatively similar studies were combined, with weighting by study size, to yield aggregate odds ratios for stroke, major hemorrhage, and death for each drug. MAIN RESULTS: Fourteen articles were included in this review. Warfarin was more efficacious than placebo for primary stroke prevention [aggregate odds ratio (OR) of stroke=0.30 [95% Confidence Interval (C.I.) 0.19,0.48]], with moderate evidence of more major bleeding [ OR= 1.90 [95% C.I. 0.89,4.04].]. Aspirin was inconclusively more efficacious than placebo for stroke prevention [OR=0.68 [95% C.I. 0.29,1.57]], with inconclusive evidence regarding more major bleeds [OR=0.81[95% C.I. 0.37,1.78]]. For primary prevention, assuming a baseline risk of 45 strokes per 1000 patient-years, warfarin could prevent 30 strokes at the expense of only 6 additional major bleeds. Aspirin could prevent 17 strokes, without increasing major hemorrhage. In direct comparison, there was moderate evidence for fewer strokes among patients on warfarin than on aspirin [aggregate OR=0.64[95% C.I. 0.43,0.96]], with only suggestive evidence for more major hemorrhage [OR =1.58 [95% C.I. 0.76,3.27]]. However, in younger patients, with a mean age of 65 years, the absolute reduction in stroke rate with warfarin compared to aspirin was low (5.5 per 1000 person-years) compared to an older group (15 per 1000 person-years). Low-dose warfarin or low-dose warfarin with aspirin was less efficacious for stroke prevention than adjusted-dose warfarin. REVIEWER'S CONCLUSIONS: The evidence strongly supports warfarin in AF for patients at average or greater risk of stroke, although clearly there is a risk of hemorrhage. Although not definitively supported by the evidence, aspirin may prove to be useful for stroke prevention in sub-groups with a low risk of stroke, with less risk of hemorrhage than with warfarin. Further studies are needed of low- molecular weight heparin and aspirin in lower risk patients.

Publication Types: 

Review 

Review, Academic 

PMID: 11279741 [PubMed - indexed for MEDLINE] 

Ann Intern Med. 2003 Dec 16;139(12):1018-33. Related Articles, Links 

Comment in: 

Ann Intern Med. 2003 Dec 16;139(12):I32.

Management of atrial fibrillation: review of the evidence for the role of pharmacologic therapy, electrical cardioversion, and echocardiography.

McNamara RL, Tamariz LJ, Segal JB, Bass EB.

Cardiovascular Section, Yale University School of Medicine, New Haven, Connecticut 06520-8017, USA. robert.mcnamara@yale.edu

PURPOSE: This review summarizes the available evidence regarding the efficacy of medications used for ventricular rate control, stroke prevention, acute conversion, and maintenance of sinus rhythm, as well as the efficacy of electrical cardioversion and the use of echocardiography in patients with atrial fibrillation. DATA SOURCES: The Cochrane Collaboration's database of controlled clinical trials and MEDLINE. STUDY SELECTION: Primarily randomized, controlled trials of medications. DATA EXTRACTION: Paired reviewers obtained data on efficacy and safety. Strength of evidence was assessed. DATA SYNTHESIS: Recent clinical trial results showed that most patients with atrial fibrillation have similar outcomes with strategies for controlling ventricular rate compared with strategies for restoring sinus rhythm. For efficacy of primary stroke prevention, compared with placebo, evidence was strong for warfarin and suggestive for aspirin. The evidence for an increased risk for major bleeding was suggestive for warfarin and inconclusive for aspirin. For ventricular rate control, verapamil, diltiazem, atenolol, and metoprolol were qualitatively superior to digoxin and placebo, particularly during exercise. For efficacy of acute conversion, compared with placebo, evidence was strong for ibutilide, flecainide, dofetilide, propafenone, amiodarone, and quinidine. For efficacy of maintenance of sinus rhythm after conversion from atrial fibrillation, evidence was strong for amiodarone, propafenone, disopyramide, and sotalol. Echocardiography was found to be useful in estimating risk for thromboembolism and potentially useful in estimating likelihood of successful cardioversion and maintenance. CONCLUSIONS: For several key questions in the pharmacologic management of atrial fibrillation, strong evidence exists to support 1 or more treatment options.

Publication Types: 

Review 

Review, Academic 

PMID: 14678922 [PubMed - indexed for MEDLINE] 

Arch Intern Med. 2002 Mar 11;162(5):541-50.

Balancing the risks of stroke and upper gastrointestinal tract bleeding in older patients with atrial fibrillation.

Man-Son-Hing M, Laupacis A.

SourceDepartment of Medicine, University of Ottawa, Geriatric Assessment Unit, Ottawa Research Institute, Ottawa Hospital (Civic Campus), 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9. mhing@ottawahospital.on.ca

Abstract

OBJECTIVE: To determine how factors that increase the risk of major upper gastrointestinal (GI) tract hemorrhage (recent upper GI tract bleeding or concurrent use of nonsteroidal anti-inflammatory drugs) influence the choice of antithrombotic therapy in older patients (those > or = 65 years) with atrial fibrillation.

METHODS: For older patients with atrial fibrillation and no other contraindications to antithrombotic therapy, a Markov decision-analytic model was used to determine the preferred treatment strategy (no antithrombotic therapy, long-term aspirin use, or long-term warfarin sodium use) based on their risk of major upper GI tract hemorrhage. Input data were obtained by a systematic review of MEDLINE. Outcomes were expressed as quality-adjusted life-years (QALYs).

RESULTS: For 65-year-old patients with average risks of stroke and upper GI tract bleeding, warfarin therapy was associated with 12.1 QALYs per patient; aspirin therapy, 10.8 QALYs; and no antithrombotic therapy, 10.1 QALYs. For persons with significantly higher risks of upper GI tract bleeding and/or lower risks of stroke, warfarin was no longer clearly the optimal antithrombotic therapy (eg, for 80-year-old persons with a baseline risk of stroke of 4.3% per year who were concurrently taking a conventional nonsteroidal anti-inflammatory drug: warfarin, 7.44 QALYs; aspirin, 7.39 QALYs; and no treatment, 7.21 QALYs).

CONCLUSIONS: For older patients with atrial fibrillation and factors that place them at a higher than average risk of upper GI tract bleeding, the optimal choice of antithrombotic therapy to prevent stroke can vary according to the magnitude of this risk. Based on the risks of stroke and upper GI tract bleeding, clinicians can use the treatment recommendations of this study to provide rational stroke prevention therapy for older patients with atrial fibrillation.

PMID:11871922

Cochrane Database Syst Rev. 2002;(1):CD002903. Related Articles, Links 

J Manag Care Pharm. 2009 Apr;15(3):244-52.

Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States.

Baker WL, Cios DA, Sander SD, Coleman CI.

SourceUniversity of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT 06102, USA.

Abstract

BACKGROUND: Atrial fibrillation (AF) affects a significant proportion of the American population and increases ischemic stroke risk by 4- to 5-fold. Oral vitamin K antagonists, such as warfarin, can significantly reduce this stroke risk but can be difficult to dose and monitor. Previous research on the effects of setting (e.g., randomized controlled trials, anticoagulation management by specialty clinics, usual care by community physicians) on the proportion of time spent within therapeutic range for the international normalized ratio (INR) has not specifically examined anticoagulation in AF patients.

OBJECTIVES: Use traditional meta-analytic and meta-regressive techniques to evaluate the effect of specialty clinic versus usual care by community physicians on anticoagulation control, measured as the proportion of time spent in therapeutic INR range, for AF patients that received warfarin anticoagulation in the United States.

METHODS: Studies included in a previously published meta-analysis (van Walraven et al., 2006), which systematically searched reports between 1987 and 2005, were also screened for inclusion in our analysis. A subsequent systematic literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Clinical Trials from January 2005 through February 2008 was conducted. Studies were included if they (a) contained at least 1 warfarin-treated group including more than 25 patients for whom INR control was monitored for at least 3 weeks; (b) included patients treated for AF in the United States; (c) used a patient-time approach (patient-year) to report outcomes; and (d) reported data on the proportion of time spent in traditional therapeutic INR ranges (i.e., a lower limit INR between 1.8 and 2.0 and an upper limit INR between 3.0 and 3.5. Studies with INR goals outside this range were excluded). The proportion of time spent within the therapeutic INR range for each study group was expressed as an incidence density using a person-time approach (in years). All studies were pooled using a random effects model and were weighted by the inverse of the variance of proportion of time spent in the therapeutic range. In order to determine how study setting influenced the proportion of time spent within a therapeutic INR range, both subgroup and meta-regression analyses were conducted.

RESULTS: This analysis included 8 studies and a total of 14 unique warfarin- treated groups; 3 of the 8 studies and 4 of the warfarin groups were not included in the previous meta-analysis (van Walraven et al., 2006). Overall, patients spent a mean 55% (95% CI = 51%-58%) of their time in the therapeutic INR range. Meta-regression suggested that AF patients treated in a community usual care setting compared with an anticoagulation clinic spent 11% (95% CI = 2%-20%, n = 6 studies with 9 study groups) less time in range.

CONCLUSIONS: In the United States, AF patients spend only about one-half the time within therapeutic INR. Anticoagulation clinic services are associated with somewhat better INR control compared with standard community care.

PMID:19326955

Electrical cardioversion for atrial fibrillation and flutter.

Mead GE, Flapan AD, Elder AT.

Clinical and Surgical Sciences, University of Edinburgh, 21 Chalmers Street, Edinburgh, UK, EH3 9EW. gmead@srv1.med.ed.ac.uk

BACKGROUND: Atrial fibrillation increases the risk of stroke, increases the risk of cognitive impairment, and adversely affects cardiovascular haemodynamics. Electrical cardioversion for atrial fibrillation has been in use since the 1960s; the rationale is that restoration of sinus rhythm improves cardiovascular haemodynamics, reduces the risk of stroke, and obviates the need for long-term anticoagulation. OBJECTIVES: To assess the effects of electrical cardioversion of atrial fibrillation or atrial flutter on the annual risk of thromboembolic events, strokes and mortality (primary outcomes measures), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcome measures) in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. SEARCH STRATEGY: One reviewer searched the Cochrane Controlled Clinical Trials Register (2000 Issue 4), MEDLINE (1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to November 2000) and proceedings of the American College of Cardiology (published in the Journal of the American College of Cardiology 1983 to 2000). Reference lists of articles were searched. Personal contact was made with experts in the field. A second reviewer handsearched proceedings of the British Cardiac Society (published in British Heart Journal (1980 to 1995) and in Heart (1995 to May 2001); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2000); scientific sessions of the American Heart Association (published in Circulation 1990-2000). SELECTION CRITERIA: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of the following: anticoagulants, antiplatelet drugs and drugs for 'rate control', in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. DATA COLLECTION AND ANALYSIS: It was planned to extract study data onto data extraction forms. The planned analysis was by the statistical package in RevMan. MAIN RESULTS: No completed randomised trials or controlled clinical trials of electrical cardioversion were found. Two ongoing trials were identified. REVIEWER'S CONCLUSIONS: There were no data from completed randomised controlled trials or controlled clinical trials to either support or refute the use of electrical cardioversion for atrial fibrillation. Randomised trials of electrical cardioversion are required.

Publication Types: 

Review 

Review, Academic 

PMID: 11869642 [PubMed - indexed for MEDLINE] 

Am J Geriatr Cardiol. 2003 Jan-Feb;12(1):49-56. Related Articles, Links 

Atrial fibrillation in the elderly.

Yadav A, Scheinman M.

Department of Medicine, Division of Cardiology, Cardiac Electrophysiology Section, University of California at San Francisco, San Francisco, CA 94143, USA. yadav@medicine.ucsf.edu

Atrial fibrillation is the most common arrhythmia in the United States, whose incidence is greatest in the elderly population. This rhythm disorder can be paroxysmal or chronic and is associated with a range of clinical conditions from palpitations and dyspnea to stroke and death. In the elderly the mainstay of treatment of atrial fibrillation should utilize drug therapy. The main goals of drug therapy should be effective rate control to avoid tachycardia-induced cardiomyopathy, anticoagulation to reduce the risk of stroke and thromboembolism, and maintenance of sinus rhythm to prevent adverse atrial remodeling. In those patients in whom effective rate control cannot be achieved, catheter ablation of the atrioventricular node and implantation of a permanent pacemaker should be considered. Catheter ablation of atrial fibrillation by targeting pulmonary venous foci or pulmonary venous isolation currently remains investigational and we advocate its use be limited to symptomatic patients who have failed traditional therapy. Copyright 2003 CVRR, Inc.

Publication Types: 

Review 

Review, Tutorial 

PMID: 12502916 [PubMed - indexed for MEDLINE] 

Arch Fam Med. 2000 Apr;9(4):389-90. Related Articles, Links 

Comment in: 

Arch Fam Med. 2000 Jul;9(7):587-8.

Vagally mediated atrial fibrillation in a young man.

Ringdahl EN.

Department of Family and Community Medicine, University of Missouri, Columbia, USA. ringdahle@health.missouri.edu

Atrial fibrillation may be provoked by either vagal or sympathetic stimulation. Sympathetic effects are common in middle-aged and elderly patients with underlying heart disease. However, in the young, non-diseased heart, vagal influences are more likely to predominate. Recognition of vagally mediated atrial fibrillation in young adults as a unique clinical entity has diagnostic and therapeutic implications.

Publication Types: 

Case Reports

PMID: 10776370 [PubMed - indexed for MEDLINE] 

Chest. 1982 Apr;81(4):429-32. Related Articles, Links 

Spontaneous conversion of long-standing atrial fibrillation.

Gardner JD, Dunn M.

Spontaneous conversion to sinus rhythm after prolonged atrial fibrillation is uncommon, with only 11 recorded cases to our knowledge in the English language literature. We report four cases of spontaneous conversion to an organized atrial rhythm (either sinus rhythm or atrial tachycardia with block) after nine to 16 years of established atrial fibrillation. One case was due to a toxic reaction to digitalis. In the other three cases there was no apparent reason. M-mode and two-dimensional echocardiography in three patients showed an akinetic and noncontractile left atrium in each case. This lends support to an earlier hypothesis that complete fibrosis of the left atrium may be responsible for the conversion from atrial fibrillation.

Publication Types: 

Case Reports

PMID: 7067507 [PubMed - indexed for MEDLINE] 

Pacing Clin Electrophysiol. 2001 Sep;24(9 Pt 1):1363-8. Related Articles, Links 

Response of atrial fibrillatory activity to carotid sinus massage in patients with atrial fibrillation.

Bollmann A, Wodarz K, Esperer HD, Toepffer I, Klein HU.

Department of Cardiology, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. andreas.bollmann@medizin.uni-magdeburg.de

In some cases carotid sinus massage (CSM) may induce AF, whereas it may terminate AF in others. The purpose of this study was to investigate the influence of CSM on atrial fibrillatory frequency using spectral analysis of the surface ECG. Continuous ECG recordings were made in 19 patients (12 men, 7 women, mean age 61 +/- 11 years) with AF. Unilateral CSM was performed in the standard fashion to one randomized bifurcation of the carotid artery at a time. Ventricular rate and fibrillatory frequency were assessed in 30-second ECG segments at baseline and during CSM. The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, subtraction of averaged QRST complexes, and Fourier transformation). CSM resulted in a relative change in fibrillatory frequency of 4.5 +/- 3.9% (range 0%-13%). In 8 (42%) patients an increase in fibrillatory frequency was found (6.4 +/- 0.5 vs 6.8 +/- 0.5 Hz, P = 0.012). In 9 (47%) patients a decrease in fibrillatory frequency occurred (6.5 +/- 0.8 vs 6.1 +/- 0.8 Hz, P = 0.008) without AF termination. The remaining two patients showed no change in fibrillatory frequency. CSM on the contralateral side after 2 minutes produced fibrillatory frequency changes in the same direction in all patients with a good reproducibility in its magnitude (r = 0.59, P = 0.05). Calcium channel blockers were more frequently used (78% vs 25%, P = 0.044) in patients with a decrease in fibrillatory frequency compared to patients with a frequency increase. There were no significant changes in ventricular rate during CSM. In conclusion, two different responses of atrial fibrillatory frequency to CSM were found. This might explain why CSM may facilitate AF induction in some cases and AF termination in others. Calcium channel blocker treatment may prevent an increase in fibrillatory frequency provoked by CSM suggesting a blunted electrical remodeling process.

PMID: 11584458 [PubMed - indexed for MEDLINE] 

Int J Clin Pract. 2001 Mar;55(2):108-14. Related Articles, Links 

Comment in: 

Int J Clin Pract. 2001 Mar;55(2):77-8.

The old but reliable digitalis: persistent concerns and expanded indications.

Abarquez RF Jr.

College of Medicine, University of the Philippines, Manila, Philippines.

Digitalis has been an old but reliable drug for 240 years. Concerns regarding its clinical indications and benefits still exist in the absence of a reduction in all-cause mortality. While intravenous digitalis is used without question in cases of atrial fibrillation, it is still controversial in sinus rhythm, despite the Digitalis Investigation Group (DIG) study showing a significant reduction in death and the need for hospitalisation for congestive heart failure in both diastolic and systolic dysfunction. The influence of digitalis in acute myocardial infarction, coronary artery disease and sudden cardiac death remains speculative. In cases of uncomplicated hypertension, it appears to prevent the onset of left ventricular dysfunction and myocardial infarction. Thus, digitalis can be a cost-effective agent with added benefits.

Publication Types: 

Review 

Review, Tutorial 

PMID: 11321850 [PubMed - indexed for MEDLINE] 

Nurs Times. 1994 Sep 21-27;90(38):36-7. Related Articles, Links 

The use of massage in restoring cardiac rhythm.

Curtis M.

There is a growing body of research that connects heart rate and massage. These variously associate massage with reduced cardiac rate, lowered blood pressure, decreased anxiety and increases in relaxation and a sense of well-being. Dunbar and Redick looked specifically at back massage following myocardial infarction and Weiss reports a correlation between touch and heart rate during tracheal suctioning. This paper describes how massage was used to restore cardiac rhythm from a state of atrial fibrillation in one patient.

Publication Types: 

Case Reports

PMID: 7971330 [PubMed - indexed for MEDLINE] 

J Am Coll Cardiol. 1993 Oct;22(4):1123-9. Related Articles, Links 

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation.

Brignole M, Gianfranchi L, Menozzi C, Raviele A, Oddone D, Lolli G, Bottoni N.

Laboratory of Electrophysiology and Pacing, Ospedali Riuniti, Lavagna, Italy.

OBJECTIVES. The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND. Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS. Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS. Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS. Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.

PMID: 8409051 [PubMed - indexed for MEDLINE] 

G Ital Cardiol. 1993 Oct;23(10):985-93. Related Articles, Links 

[Hypersensitivity and carotid sinus syndrome in patients with chronic atrial fibrillation]

[Article in Italian]

Cicogna R, Mascioli G, Bonomi FG, Turelli A, Morandi F, Curnis A, Visioli O.

Cattedra e Divisione di Cardiologia, Universita Degli Studi e Spedali Civili, Brescia.

BACKGROUND. Carotid sinus hypersensitivity (CSH) has always been described in patients in sinus rhythm; we did not find reports of CSH in patients with chronic atrial fibrillation (AF). After the observation of bilateral CSH in a patient with chronic AF admitted to our Division for syncope, we began to systematically study patients with chronic AF and neurological disturbances to evaluate carotid sinus stimulation effects upon cardiac activity and arterial blood pressure in these subjects. METHODS. We studied 28 subjects with chronic AF (mean age 73.3 yrs.; range 60-89): 16 patients had dizziness, fainting or syncope, and formed the study group (A); 12 asymptomatic patients were considered the control group (B). After a careful clinical and instrumental evaluation, all the patients underwent a 24 hour ambulatory (Holter) ECG analysis and right and left carotid sinus massage (CSM). If the latter manoeuvre induced asystolia longer than 3 seconds, CSM was repeated during ventricular pacing to evaluate the vasal component of the carotid sinus reflex. RESULTS. In group A, 24-hour Holter monitoring showed a greater incidence (81.2%) of ventricular standstill (mean duration 2.67 seconds) in comparison to the control group. In group A we found CSH in 75% of the cases, more frequently right CSH (7 subjects with right, 1 with left and 4 with bilateral CSH) with prolonged ventricular asystolia (mean duration 5.3 +/- 1.9 sec. with right CSM; 7.8 +/- 1.4 sec. with left CSM); during CSM, we reproduced spontaneous symptomatology in 9 patients. In 12 patients in group A, diagnosis of carotid sinus syndrome was established; the cardioinhibitory forms were clearly prevalent (91.7%); only one patient presented a cardioinhibitory-vasodepressor form with a predominant vasodepressor component. CONCLUSIONS. The authors believe that CSH is frequent in patients with chronic AF; the vagal hyperactivity due to CSH can induce prolonged ventricular asystole that may be responsible for neurological disturbances such as dizziness, fainting or syncope, as observed in patients in sinus rhythm with carotid sinus syndrome. Abnormal sensitivity of the carotid sinus could thus be one of the causes of increased morbidity and mortality in patients with chronic AF. The majority of these patients may be expected to benefit from permanent pacemaker therapy.

PMID: 8174866 [PubMed - indexed for MEDLINE] 

Biull Eksp Biol Med. 1987 Aug;104(8):151-3. Related Articles, Links 

[Prevention of a stress-induced drop in the threshold of cardiac fibrillation using transauricular electroacupuncture]

[Article in Russian]

Radzievskii SA, Vorontsova EIa, Chuvil'skaia LM, Ustinova EE, Meerson FZ.

The effect of electroacupuncture on stress-induced drop in cardiac fibrillation threshold and catecholamine content in the adrenergic terminals of the myocardium was studied in Wistar rats. Transauricular electroacupuncture causing drowsiness in animals was found to prevent a drop in cardiac fibrillation and norepinephrine level in the adrenergic terminals usually observed after long immobilization stress. It is assumed that the preventive effect of acupuncture may be attributable to reflex activation of the inhibitory brain system which restricts stress reaction.

PMID: 3620666 [PubMed - indexed for MEDLINE] 

Ugeskr Laeger. 2003 Apr 28;165(18):1868-71. Related Articles, Links 

[Effect of Coenzyme Q10 and Ginkgo biloba on warfarin dosage in patients on long-term warfarin treatment. A randomized, double-blind, placebo-controlled cross-over trial]

[Article in Danish]

Engelsen J, Nielsen JD, Hansen KF.

Klinisk Biokemisk Afdeling, Koagulationslaboratoriet, Amtssygehuset i Gentofte, Niels Andersens Vej 165, DK-2900 Hellerup. jeng@dadlnet.dk

INTRODUCTION: A few case-stories claim that the anti-oxidant Coenzyme Q10 and possibly also Ginkgo biloba interact with warfarin treatment. A decreased response to warfarin in the Coenzyme Q10 cases and an increased response in the Ginkgo biloba case have been described. MATERIAL AND METHODS: Twenty-four outpatients on stable, long-term warfarin treatment were included in a randomised, double blind, placebo-controlled crossover trial. Coenzyme Q10 100 mg daily, Ginkgo-Biloba 100 mg daily and placebo were given in random order over treatment periods of four weeks, each followed by a two week wash out period. The international normalized ratio (INR) INR was kept between 2.0 and 4.0 by appropriate adjustment of the warfarin dosage. RESULTS: Fourteen women and ten men, median ages 64.5 years (33-79) were included. Three patients withdrew from the study for personal reasons. The INR was stable during all treatment periods. The geometric mean dosage of warfarin did not change during the treatment periods: Ginkgo biloba 36.7 mg/week (95% confidence interval: 29.2-46.0); CoQ10 36.5 mg/week (29.1-45.8); placebo 36.0 mg/week (28.6-45.1). CONCLUSION: The study indicated that Coenzyme Q10 and Ginkgo biloba do not influence the clinical effect of warfarin.

Publication Types: 

Clinical Trial 

Randomized Controlled Trial 

PMID: 12772396 [PubMed - indexed for MEDLINE] 

Neurol Res. 2000 Jul;22(5):517-21. Related Articles, Links 

Protective effect of ginkgo extract on rat brain with transient middle cerebral artery occlusion.

Zhang WR, Hayashi T, Kitagawa H, Sasaki C, Sakai K, Warita H, Wang JM, Shiro Y, Uchida M, Abe K.

Department of Neurology, Okayama University Medical School, Japan. zhang@cc.okayama-u.ac.jp

It has been empirically known that Ginkgo extract is useful for reducing many symptoms associated with cerebral blood flow (CBF) insufficiency, but its mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo extract to rats with per os digestion, and investigated its effect on CBF and ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment with Ginkgo extract (10 mg 100 g-1 rat) increased CBF in the normal condition, but the degree of increase in CBF was lesser during and after MCAO. TTC staining showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72 immunostaining confirmed the protective effect of Ginkgo treatment reducing numbers of TUNEL and HSP72 positive cells. Immunohistochemical analysis showed that caspase-3 expression was less abundant in Ginkgo treated rats. The present results suggest that Ginkgo extract contains a substance which increases normal CBF and reduces ischemic brain damage.

PMID: 10935227 [PubMed - indexed for MEDLINE] 

Neurology. 2003 Nov 11;61(9):1273-5. Related Articles, Links 

Dietary antioxidants and the risk of ischemic stroke: the Rotterdam Study.

Voko Z, Hollander M, Hofman A, Koudstaal PJ, Breteler MM.

Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, The Netherlands.

In the Rotterdam Study, the authors investigated whether high intake of antioxidants from food is associated with the risk of stroke. Among 5,197 participants who were followed on average for 6.4 years, 227 ischemic strokes occurred. Higher intake of antioxidants was associated with a lower risk of stroke. The relationship was dose-dependent, significant for vitamin C, and most pronounced in smokers. These results agree with the view that high dietary intake of antioxidants, in particular vitamin C and--in smokers--vitamin E, reduces the risk of stroke.

PMID: 14610137 [PubMed - indexed for MEDLINE] Stroke. 2003 Oct;34(10):2355-60. Epub 2003 Sep 18. Related Articles, Links 

Vegetable and fruit intake and stroke mortality in the Hiroshima/Nagasaki Life Span Study.

Sauvaget C, Nagano J, Allen N, Kodama K.

Department of Epidemiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, 732-0815 Hiroshima, Japan. sauvaget@rerf.jp

BACKGROUND AND PURPOSE: Fruits and vegetables are known for their beneficial effects on chronic diseases. The purpose of the present study was to investigate the protective effect of a diet rich in fruits and vegetables on total stroke mortality and its 2 main subtypes in men and women separately. METHODS: A prospective cohort study of 40 349 Japanese men and women was initiated in 1980-1981 and followed until 1998. Fruit and vegetable intake was assessed at baseline on the basis of the response to a food frequency questionnaire. During the 18-year follow-up period, deaths from stroke were registered. RESULTS: A total of 1926 stroke deaths were identified during the follow-up period. An increasing frequency of intake of green-yellow vegetables and fruit was associated with a reduced risk of death from intracerebral hemorrhage and cerebral infarction. Daily intake of green-yellow vegetables was associated with a significant 26% reduction in the risk of death from total stroke in men and women compared with an intake of once or less per week. The protective effect associated with daily fruit and vegetable intake was observed for both cerebral infarction and intracerebral hemorrhage mortality but was slightly stronger and clearer for infarction than for hemorrhage, with a 32% reduction in men and a 30% reduction in women. Daily fruit intake was associated with a significant 35% reduction in risk of total stroke in men and a 25% reduction in women and was equally strong for both intracerebral hemorrhage and cerebral infarction. CONCLUSIONS: Daily consumption of green-yellow vegetables and fruits is associated with a lower risk of total stroke, intracerebral hemorrhage, and cerebral infarction mortality. The protective effects are similar in both men and women.

PMID: 14500940 [PubMed - indexed for MEDLINE] 

Am J Clin Nutr. 2003 Jul;78(1):57-64. Related Articles, Links 

Intake of fruit and vegetables and the risk of ischemic stroke in a cohort of Danish men and women.

Johnsen SP, Overvad K, Stripp C, Tjonneland A, Husted SE, Sorensen HT.

Department of Clinical Epidemiology, Aarhus University Hospital and Aalborg Hospital, Aarhus, Denmark. spj@soci.au.dk

BACKGROUND: Previous studies have suggested that a high dietary intake of fruit and vegetables is associated with a reduced risk of ischemic stroke. The magnitude of the effect is uncertain, and only one study reported data on the intake of specific fruit and vegetables and the risk of stroke. OBJECTIVE: We examined whether the intake of fruit and vegetables is associated with a reduced risk of ischemic stroke, with particular attention paid to specific fruit and vegetables and subtypes of ischemic stroke. DESIGN: In a prospective cohort study of 54,506 men and women who were included in the Danish Diet, Cancer, and Health study from 1993 to 1997, estimated total intakes of fruit and vegetables (in g/d) were extracted from a semiquantitative food-frequency questionnaire completed at baseline. Data about subjects hospitalized with ischemic stroke were obtained from the Danish National Registry of Patients and were verified later by record reviews. The follow-up for ischemic stroke ended on the date of a first hospital admission for stroke or transient ischemic attack, the date of death or emigration, or the end of the study, whichever came first. RESULTS: We identified 266 cases of ischemic stroke involving hospitalization during 168,388 person-years of follow-up (median follow-up: 3.09 y; range: 0.02-5.10 y). After adjustment for potential confounders, persons in the top quintile of fruit and vegetable intake (median: 673 g/d) had a risk ratio of ischemic stroke of 0.72 (95% CI: 0.47, 1.12) relative to persons in the bottom quintile of intake (median: 147 g/d) (P for trend = 0.04). When comparing the top quintile with the bottom quintile, an inverse association was most evident for fruit intake (risk ratio: 0.60; 95% CI: 0.38, 0.95; P for trend = 0.02). Similar risk estimates were seen for most types of fruit and vegetables, although the risks were significant only for citrus fruit. CONCLUSION: An increased intake of fruit may reduce the risk of ischemic stroke.

PMID: 12816771 [PubMed - indexed for MEDLINE] 

Heart. 2011 Apr 8. [Epub ahead of print]

Prevention of atrial fibrillation with omega-3 fatty acids: a meta-analysis of randomised clinical trials.

Liu T, Korantzopoulos P, Shehata M, Li G, Wang X, Kaul S.

SourceCedars-Sinai Medical Center, Los Angeles, California, USA.

Abstract

Context Previous randomised controlled trials (RCT) regarding n-3 PUFA supplementation for atrial fibrillation (AF) prevention have yielded conflicting results. Objective A systematic review and meta-analysis of RCT was conducted to examine the role of n-3 PUFA in AF prevention. Data Sources MEDLINE, Web of Science and Cochrane clinical trials database were searched until November 2010. Study Selection Of 127 initially identified studies, 10 RCT with 1955 patients were finally analysed. Data Extraction Two blinded reviewers extracted data independently to a predefined form. Disagreements were resolved through discussion and consensus. Results n-3 PUFA had no significant effect on the prevention of AF (OR 0.81, 95% CI 0.57 to 1.15; p=0.24). There was significant heterogeneity among the studies (p=0.002, I(2)=65.0%). Subgroup analysis showed no significant beneficial effect of fish oils in any subset of population. Conclusions No significant effects of n-3 PUFA supplementation on AF prevention were observed in this meta-analysis. A large-scale trial with higher doses and longer follow-up might be required to rule out the possibility of any treatment benefit.

PMID:21478384

Health Technol Assess. 2008 Jun;12(28):iii-iv, ix-95.

Intravenous magnesium sulphate and sotalol for prevention of atrial fibrillation after coronary artery bypass surgery: a systematic review and economic evaluation.

Shepherd J, Jones J, Frampton GK, Tanajewski L, Turner D, Price A.

SourceSouthampton Health Technology Assessments Centre, University of Southampton, UK.

Abstract

OBJECTIVES: To assess the clinical and cost-effectiveness of magnesium sulphate compared with sotalol, and to assess the clinical effectiveness of magnesium sulphate compared with placebo in the prevention of atrial fibrillation (AF) in patients who have had a coronary artery bypass graft (CABG).

DATA SOURCES: Major electronic databases were searched from December 2003 to May 2007.

REVIEW METHODS: Selected studies were assessed, subjected to data extraction using a standard template and quality assessment using published criteria. A simple short-term economic model was developed, informed by a systematic review of economic evaluations and populated with data from a review of costing/resource-use studies and other published studies. The cost-effectiveness of magnesium sulphate as prophylaxis was estimated for a set of base-case assumptions and the robustness of these results was assessed using deterministic and probabilistic sensitivity analysis.

RESULTS: Twenty-two papers met the inclusion criteria reporting 15 trials which all compared magnesium sulphate with placebo or control. They ranged in size from 15 to 176 patients randomised, and were conducted in Europe, the USA and Canada. The standard of reporting was generally poor, with details of key methodological attributes difficult to elucidate. No trials were identified that specifically aimed to compare magnesium sulphate with sotalol. Of 1070 patients in the pooled magnesium group, 230 (21%) developed postoperative AF, compared with 307 of 1031 (30%) patients in the placebo or (control) group. Meta-analysis using a fixed-effects model generated a pooled odds ratio (OR) that was significantly less than 1.0 [OR=0.65, 95% confidence interval (CI) 0.53 to 0.79, test for overall effect p<0.0001], but with statistically significant heterogeneity (I2=63.4%, p=0.0005). Two randomised controlled trials (RCTs) were notable as they had relatively lower ORs in favour of magnesium sulphate. When these were removed from the analyses the pooled OR remained statistically significant, but heterogeneity no longer remained significant. These two studies tended to impart a highly significant reduction in the odds of AF to whichever subgroup they were analysed in. When studies were ordered by total duration of prophylaxis, an apparent relationship between duration and odds of AF was evident, with decreasing odds of AF as duration of prophylaxis increased. This was confirmed by linear regression analysis (R2=0.743, p<0.001). When the data were grouped into three classes according to duration, a statistically significant intervention effect was only present for the longest duration (OR=0.12, 95% CI 0.06 to 0.23, p=0.00001). Statistically significant intervention effects were associated with the initiation of prophylaxis 12 hours or more before surgery (OR 0.26; 95% CI 0.16 to 0.44, test for overall effect p=0.00001, fixed-effects model) and less than 12 hours before surgery or during the surgery itself (OR=0.73, 95% CI 0.56 to 0.97, test for overall effect p = 0.03, fixed-effects model), but not when prophylaxis was initiated at the end of surgery or postsurgery (OR=0.85, 95% CI 0.59 to 1.22, p=0.37, fixed-effects model). When studies were ordered by total dose of intravenous magnesium sulphate (<25 g), the odds of AF were independent of the dose. A notable exception was that for a total dose of 9 g magnesium sulphate; here the odds of AF were significantly reduced relative to the control group, although this may be explained by the fact that these studies had excluded patients who were on antiarrhythmic drugs and so may have been at higher risk of AF. Sixty-three potentially relevant references about cost-effectiveness were identified, but no economic evaluations of intravenous magnesium alone as prophylaxis against AF following CABG, compared with sotalol as prophylaxis or no prophylaxis, were identified. Studies reporting resource use by patients with AF following CABG suggest that while AF significantly increased inpatient stays, by up to 2.3 days in the intensive care unit (ICU) and 3.4 days on the ward, differences in length of stay and costs between patients receiving prophylaxis and those not receiving prophylaxis were not statistically significant. In the base-case analysis, magnesium sulphate prophylaxis resulted in 0.081 fewer cases of AF at an incremental cost of 2.55 pounds sterling. The incremental cost-effectiveness ratio (ICER) was 32 pounds sterling per AF case avoided. The estimated difference in average length of stay between the prophylaxis and no-prophylaxis strategies was only 0.24 days, despite a large assumed difference of 3 days for patients experiencing AF in each group (1 extra day in the ICU and 2 extra days on the ward). In a deterministic sensitivity analysis the greatest variation in ICERs was observed for input parameters relating to the baseline risk of AF following CABG and the effectiveness of prophylaxis, cost of prophylaxis and the resource consequences of postoperative AF. The largest ICER (2092 pounds sterling) in the sensitivity analysis was associated with increasing the length of patients' preoperative stay. In the base case it was assumed that admission routines would be identical under both strategies. However, patients receiving prophylaxis by intravenous infusion may have longer preoperative stays. In a probabilistic analysis the majority of the simulations were associated with improved outcomes (in this case fewer cases of AF), but also higher costs. Prophylaxis was the dominant strategy (better outcome at lower cost) in about 41% of the simulations using the base-case assumptions. Under an alternative scenario where patients receiving prophylaxis are admitted for longer before their operation, to receive their initial infusion, the proportion of simulations where prophylaxis dominates fell to around 5%. The probability of being cost-effective was 99% at a willingness to pay (WTP) threshold of 2000 pounds sterling per AF case avoided and 100% at a WTP threshold of 5000 pounds sterling per AF case avoided under the base-case assumptions. Under the alternative scenario of longer preoperative stays the probability of being cost-effective at these two threshold values fell to 48% and 93%, respectively. It is unclear what the appropriate decision threshold should be, given that this model used intermediate rather than final outcomes.

CONCLUSIONS: No RCTs were identified that specifically aimed to compare intravenous magnesium with sotalol as prophylaxis for AF in patients undergoing CABG. Intravenous magnesium, compared with placebo or control, is effective in preventing postoperative AF, as confirmed by a statistically significant intervention effect based on pooled analysis of 15 RCTs. It was also found that AF was less likely to occur when a longer duration of prophylaxis was used, and the earlier that prophylaxis is started; however, this finding was associated with two RCTs that had more favourable results than the other trials. No clear relationship between dose and AF was observed, although a lower constant dose rate was associated with the lowest odds of AF. Further research should investigate the relationship between dose, dose rate, duration of prophylaxis, timing of initiation of therapy and patient characteristics, such as degree of risk for AF. This will provide stronger evidence for the optimum delivery of intravenous magnesium in patients undergoing CABG. In the base-case analysis in the economic model, magnesium sulphate prophylaxis reduced the number of postoperative AF cases at a modest increase in cost. The results of the economic analysis are highly sensitive to variation in certain key parameters. Prophylaxis is less likely to be a cost-effective option if it requires changes in admission routines that result in longer preoperative stays than would be the case without prophylaxis.

PMID:18547499

Hi, I’m Christopher Maloney and I’m here to talk about biochemistry. Specifically the biochemistry of happiness. I know how excited all of you must be, here on a Friday to hear a lecture on biochemistry. Makes your toes twitch with happiness, doesn’t it? 

Google doc link of lecture with footnotes

Meet my three friends of happiness

1. Dopey (Breath and attention)

2. Smiley (Me and meaning)

3. Angry (People and quality)

4. Think of them as the three little dwarves that live in your brain, but not in a Snow White sort of way. More like a South Park sort of dwarf, who will really kick your butt if you don’t pay attention.

SPA to MAA, because frosh kept looking for hot tubs. 

Is is MEAA like a cat? Or Ma-A like a singer?

I understand not going with with Big Bang Theory’s Shelton’s MEMA

But what about MAMA? 

I know it’s not very cool, but hear me out. 

If you had a youth orchestra, it would be YO MAMA.

And if you had a famous cellist come play here, you could advertise:

Yo Yo Ma accompanied by YO MAMA. 

That would be really fun.

If you even smiled, I just altered two of the main chemicals I’m going to talk about today, my friends dopey and smiley. We’ll get to them in a second. 

Naturopathic Doctor 

1. Doctor of last resort metastatic cancer

2. Doctor of Chronic Illness that will not get better.

3. A Jack of all trades in a specialist world.

4. I have a phobia of needles. I faint, at odd times. If you’re going to stick me with a needle, I will start to hyperventilate, I will think about it for days, I will literally lose my mind. But I can take off your toenails no problem. It’s just me getting stuck that freaks me out.

The average person today has an attention span of less that 8 seconds, and I’ve maybe got seven minutes if I’ve somehow interested you enough. Since many of you are already lost in fantasy, and I’ll lose most of you in about three minutes, I’d like to demonstrate happiness and why we need to constantly pursue it in the next ten seconds. 

1. I need you all, when I say go, to hold your breath for five seconds. 

2. Ready, Go! Five, four, three, how much do you want a breath? Two, do the seconds seem to be getting longer? One, breathe. 

3. That feeling you get when you can breathe is happiness, a washing of happiness chemicals dopey, smiley, and maybe a little angry in your brain. Maybe the next breath feels good too. But in three minutes you won’t even notice your breath. Happiness fades. Change happens. Our brains crave change, they want to pursue happiness. 

4. If you forget everything else I say today, remember that happiness is a moving target because the brain becomes used to whatever is your “normal.” That’s why people who are disabled in an accident and people who win the lottery have about the same level of happiness after a year. They’ve adapted to the new normal. 

Your body runs your emotions

1. Your emotions are based in your limbic system at the base of your brain. 

2. What you think should make you happy won’t make you happy.

3. Things that are “bad” for you will often make you happy because they represent a win of the body over your stuck up brain.

4. We can literally wire up your pleasure centers in the base of your brain so that all you need to do to be happy is push a button. When we do this with rats, they will just push the button rather than eat or drink until they die. We’ve all seen stories about people who do this, it’s called doing drugs, and it’s a lot less effective or fun than the electrodes. Human studies of the electrodes have been done for highly unethical reasons, like trying to convert someone who was gay into being straight. 

5. Why don’t we all hook up to electrodes? Because we don’t just want to be happy, we want to feel like that happiness has meaning. We’ll get to that in a bit, but I need to talk about the three main chemicals that are released when you experience happiness.

Meet my three friends of happiness

1. Dopey

2. Smiley

3. Angry

4. Think of them as the three little dwarves that live in your brain, but not in a Snow White sort of way. More like a South Park sort of dwarf, who will really kick your butt if you don’t pay attention.

Let’s talk about Dopey

1. Dopey is your dopamine pathway. It triggers your pleasure centers. It’s why you like getting likes, why every successful ap on the phone is set up to trigger minor rewards. It’s also set up to trigger minor delays and occasional random rewards to maximize your dopamine release in your brain.

2. The same techniques that get you hooked online are the techniques perfected by the gambling industry. They hook you in and keep you playing because you keep getting just enough random dopamine. Dopamine can also be altered by prescription drugs. Abilify, which is used for a variety of reasons in young people, can cause pathological gambling in some people because it alters your brain dopamine.

3. The reason that dopamine is dopey is that you get to decide what makes you feel rewarded. You literally could convince yourself that getting slapped in the face is rewarding thing. Entire cultures have formed very bizarre social rewards for terrible behavior. So consciously examining what you do for short term reward and gradually altering that behavior is a key to happiness.

Altering dopamine response.

1. Let’s give a highly hypothetical situation that I’m sure will never apply to anyone in this room. Let’s say you receive social rewards for drinking too much or using drugs. 

2. Stopping drinking or using drugs deprives you of not only that physical response, that physical burst of dopamine. It removes you from your social group, so you aren’t getting your likes, or your texts, or all the online things that you have associated with social reward. You are literally cast out because you don’t engage in that behavior any more. 

3. So to make a permanent change, you need to create a separate reward system. Some people find a social group with meetings like Alcoholics Anonymous. But others need to find another social group that finds fun without using substances.

4. If you find yourself in that situation, there are always choices. Using far less is completely acceptable as long as you continue to “act” as drunk. You can also claim to already have had enough and as long as you act a little drunk, you’ll be accepted. The social structure is normally based on the appearance of overdrinking rather than overdrinking itself. Dancing anecdote. 

5. Creating alternative activities and moving some members of your group into those activities will buffer your social isolation and continue to provide you with that dopamine response without the “cold turkey” social withdrawal. 

Realize that any activity, repeated, will have a gradual decline in dopamine levels.

1. If you’ve ever played a video game, the first time you do a level, you get a lot of dopamine. The twentieth time, you just want to move on.

2. Life done the same way all the time is going to be boring. It’s not going to reward you.

3. Change is necessary simply to maintain your current level of happiness. Welcome it. 

4. Who Moved My Cheese? Talks about how at every level of your life, you need to move on when you’re no longer receiving the dopamine you need to be happy. Do not ignore the feeling that life is blah. Find out what makes it exciting again.

Here are some dopamine producing exercises.

1. Many people cannot twist their tongues into a u shape

2. Others cannot talk while breathing in

3. Others cannot raise just one eyebrow

4. Very few can lick their elbows

5. Most people find it difficult to tickle themselves

6. Many people find it difficult to put their hands together in both directions (with the index fingers reversing positions) 

If you can do any of these things, you’re special. Feel that dopamine surge? Social reward yourself every time you do something someone else can’t do. Walking and breathing count. 

Proper dopamine levels can be maintained by exercise, sleep, and a variety of foods high in tyrosine. 

I’ve wanted to die, and I’ve wanted to live.

1. When I was 18, my parents divorced. I convinced myself that it was my fault. I tortured myself. Remember my fear of needles? I did that with why I should be alive. Over and over and over again. Until the only thing I wanted to do was die. I made a plan, I started to carry out my plan, climbing up a 150 train trestle in the dead of winter, my hands slipping on the cold bars...spoiler alert, I survived. But it took me years to work through and around all the evil tapes I had created. (I now know the simple solution is to write down the opposite of those tapes and read it to yourself three times a day until it sticks. I literally laughed out loud at myself the first time I said “Every day, in every way, with God’s help, I’m getting better and better.” It took me thirty repetitions before I was willing to even consider it. I spent about three years being deeply philosophical and deeply depressed. Coincidentally, it was the best three years of dating I ever had. People were just drawn to me, and I literally didn’t care. 

2. When I was 45 years old, three years ago, I was diagnosed with colon cancer. I had a 70% chance of being dead within the year. Spoiler alert, I’m still here. But I remember weeping in the car, saying I didn’t want to go yet. I’m not ready to leave. Remember, I’m still the same guy who wanted to go in his early twenties, who spent all my best dating years reading Hume, Nietzsche, and Foucault and ruminating on the nature of existence. 

3. How did I go from someone so unhappy he wanted to end it all to someone so happy with his life that he literally was willing to go through 10 out of 10 screaming pain and surgery to stay alive?

What you think is important may not be important.

1. Think of the most important thing in your life.

2. You’re wrong. I’m wrong too. We all get it wrong.

3. Now, when I say go, let’s all hold our breaths. I’ll be holding my breath as well, holding onto the thing I think is most important to me. Raise your hand when taking another breath is the more important thing. Go.

What you just experienced was a medical term called “patent airway.” 

1. It is why ER doctors aren’t worried about you. You’re breathing, whatever pain you have isn’t a big deal to them.

2. It’s also an introduction to why your willpower can’t get you through life.

3. Welcome to the first lesson is figuring out who you are and what makes you happy. 

Let’s talk about my friend smiley

Serotonin

1. Serotonin is a sedating, calming pathway that helps all the parts of your brain. It also affects your gut through fifteen different receptors divided into seven families. Half of them help with depression, half of them can make it worse.

2. SSRIs are the drugs that keep serotonin in your brain longer. They work on anxiety short term.

3. SSRIs do not produce serotonin.

4. As the body gets exposed to more serotonin, it responds less.

5. SSRIs are not overall very effective long term (a year or more), for many people.

6. Tryptophan produces serotonin. Adding tryptophan to your diet will increase the effectiveness of an SSRI. Tryptophan is found in all proteins, but particularly in turkey and warm milk. 

7. Serotonin and dopamine are often released together.

As a doctor, I’m an expert in unhappiness. I see suffering of all kinds.

1. A 17 y.o. Model who hates her body because she thinks she’s too thin.

2. An NFL football player who hates his life because he lost his girlfriend.

3. People in paroxysmal back pain that isn’t made better by drugs.

I see happiness and sadness unrelated to physical suffering.

1. The woman who cried herself into chronic heart failure

2. The five year metastatic cancer patient who felt no pain.

3. The man with the Calypso heart who wanted to sail the world.

I see death

1. A woman so afraid she was on hospice for a year and a half, exhausting her family.

2. Another woman who died of throwing up rather than cancer. She had nowhere to go when she died because her husband had thrown her out.

3. A man who passed so quickly the EMTs couldn’t save him. His wife and family celebrated his life and had a party for him. 

Angry

1. I thought about talking about endophins or oxytocin, but those are the hormones of pain relief after stress and the hormones of physical closeness. I hope all of you know that physical exercise, just walking for an hour, can be brain altering. I also hope you’re all familiar with the idea of having friends you can touch is way more important than your so-called thumb friends online. Spend time walking with your tribe, it’s hardwired for happiness. 

2. So the third hormone I want to touch on today is your angry hormone. It’s a hormone that is so common online, or when you’re driving, and it’s the opposite of happiness. It’s the “you don’t treat me like a human being, so you should die” craziness.

3. The hormone is called GABA, or the gabanergic pathway in our brains. We don’t hear as much about it, because a lack of gaba isn’t very recognized. Gaba is normally created for us by a healthy gut. So yes, what I’m saying is that all the trolls online are probably mostly reacting to their own irritated bowels and blaming you for it. 

4. We do have a group that have no GABA receptors in their brains. I did a book on this group, and I have a dear friend who has the lack. He is the sweetest human being, no impulse control. He’ll hug you at a moment’s notice. And then, when you cross him, he’ll tell you he hates you and physically go after you. At least he did when he was six. He’s getting better. But he still seems really immature for his age, because he doesn’t have a working GABA pathway. If you think about it, anyone online who is trashing on another human being is expressing that same immaturity. 

5. Why does a person without enough GABA become angry? They’re trapped. Gaba affects both anxiety and depression. A person feels what they think is inescapable stress, develops a hopeless response, and lashes out. We see this in adults who don’t know what to do to make their own lives better. They find an external reason for their problem and lash out. Responding to their criticisms logically does nothing because you’re not treating the underlying anxiety and helplessness that the person may not even acknowledge. For five years, I spent my time online trying to understand and logically address the concerns of an international group of skeptics. What I found was that logic and science were only the thin veneer over a group of people who were deeply sad to the point of madness. When we say don’t feed the trolls, it’s because they’re crazy. If you wouldn’t try to talk down someone screaming on the street, then don’t try it in online.Oh, and yes, they will die sooner than the rest of us. We have 45 studies to prove it. So don’t worry, they’ll get theirs.

6. How does Gaba help with anxiety and depression? It sedates both. We have drugs that mimic Gaba (Valium, Xanax, Ativan) in the brain. 

7. We’ve also got an over-the-counter supplement called GABA that doesn’t cross into the brain but affects the whole balance positively in the body. I’ve seen it turn kids who would punch their moms or get in trouble with the police chill out and become “normal.” 

8. We now think that GABA may be more of a factor in severe depression than even serotonin.

9. Good sources to increase GABA in your diet are beans and nuts. A number of supplements can increase them as well. But remember that your gut bacteria should produce GABA for you. I wrote a book on Tending Your Internal Garden that talks about resetting your gut bacteria safely. 

Putting it together.

1. How do you stay happy? You don’t. Every day you commit to the pursuit of your own happiness. Some days you fail. 

2. How do you get happy? You pursue meaningful goals. 

3. What are meaningful goals for you? I don’t know. Maybe you want to build a pink coral castle in Florida. Maybe to you want to build a cathedral by yourself. Maybe you want to make the most Guinness World Records

4. What we’re talking about is the quality of your life. In medical terms, we value “quality of life” on or above length of life in many older people. 

5. What is quality? I don’t know. But I know you can know it when you see it. A quality whoopie pie has completely different characteristics than a quality motorcycle. Most of us would know instantly that soft and chocolately aren’t going to help Harley Davidson sell a motorcycle. But zero to sixty in two seconds is only a good whoopie pie trait if you’re planning to throw it at someone. 

6. Knowing yourself isn’t optional. Believe me, I’ve majored in ignorance of myself. To this day I only know I’m happy because I’m humming. My brain is a huge obstacle to my happiness. I’ve always been fascinated by medicine. I love learning about the body. But I told myself that medicine wasn’t an option because of my needle fear. I can do most things, and I suck at some things. But very, very few things are going to get me up in the morning excited day after day, year after year. The thing about passion is to figure out how it can pay you. Do what makes you happy, because you’ll only be mediocre at everything else. If you want to truly succeed, you have to figure out what you’ll do for free, then figure out how to get paid enough to support yourself. That’s it. 

7. What makes you happy? It’s simple. If you currently have something you do for fun, that you obsess about, that’s what makes you happy. If you don’t, then you don’t know what makes you happy yet. Trust me, when you find your thing, I won’t be able to drag you away from it. But for some of you it may be raising small kids, or taking care of old people, or driving truck, or raising tropical fish. You may not have tried it yet. 

8. Once you find your thing, make a big goal that seems impossible. Then make really silly, small goals that you can do every day. Set yourself up for reward on a daily basis, something that is very doable and still meaningful. If you do this for three weeks you’ll set up a habitual dopamine response that will carry you through the tough times. 

9. Say your big goal is to become the next Beyonce. Your small goal should be to learn one thing about Beyonce’s career every day, and maybe sing a scale. That’s it. Not even a song. Just a scale. Everything else is gravy. By singing a little and learning a little every day, you’ll keep yourself focused on your goal without losing hope, without using your willpower to force yourself to do more.

10. Will it make you better? Yes, but you can still fail. You’ll be primed for a talent competition, for an opportunity to sing. More importantly, you’ll take any failure and use it to learn how to do better. If you don’t fail, you haven’t pushed yourself. But knowing how to reward yourself, how diet can affect your mood, and that you have to listen to your body when it says it’s done with something, will help you find happiness.

Thank you. 

A modified Mediterranean diet with particular attention paid to soy and greens. Avoid excess supplements?

Nutr Cancer. 2013;65(6):820-6. doi: 10.1080/01635581.2013.804939.

Are diet quality scores after breast cancer diagnosis associated with improved breast cancer survival?

Izano MA, Fung TT, Chiuve SS, Hu FB, Holmes MD.

Source

The Channing Division of Network Medicine, Department of Medicine , Brigham and Women's Hospital and Harvard Medical School , Boston , Massachusetts , USA.

Abstract

Previous studies have found that diets rich in fruits and vegetables are associated with reduced breast cancer mortality. However, these eating patterns do not necessarily reflect overall diet quality. The association of breast cancer mortality with a priori defined dietary scores, which are based on recommended dietary guidelines and reflect diet quality, has not been evaluated. We hypothesized that diet quality indices based on recommended guidelines are associated with decreased risk of breast cancer and nonbreast cancer mortality in breast cancer survivors. We examined the association between the Dietary Approaches to Stop Hypertension (DASH) score, and the Alternative Healthy Eating Index (AHEI)-2010, and the risk of breast cancer mortality and total mortality among women from the Nurses' Health Study diagnosed with breast cancer. Adherence to DASH-style and AHEI-2010 diets were associated with reduced risk of nonbreast cancer mortality (comparing the fifth quintile with the first quintile, relative risk (RR) = 0.72, 95% confidence interval (CI): 0.53-0.99, P trend = 0.03 for DASH, and RR = 0.57, 95% CI: 0.42-0.77, P trend <0.0001 for AHEI-2010). Diet scores were not significantly associated with breast cancer mortality. Our findings suggest that adherence to a higher quality diet after breast cancer diagnosis does not considerably change the risk of breast cancer death and recurrence. However, healthy dietary choices after breast cancer were associated with reduced risk of nonbreast cancer mortality in women with breast cancer. 

PMID: 23909725

Nutr Cancer. 2011;63(3):381-8. doi: 10.1080/01635581.2011.535963.

Diet quality indices and postmenopausal breast cancer survival.

Kim EH, Willett WC, Fung T, Rosner B, Holmes MD.

Source

Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts 02115, USA. ehjkim@post.harvard.edu

Abstract

Research on diet in breast cancer survival has been focused on single nutrients or foods, particularly dietary fat, fruits, vegetables, fiber, and alcohol. We hypothesized that diet quality indices decrease the risk of total and non-breast-cancer-related deaths in women diagnosed with breast cancer. We evaluated 4 dietary quality scores: Alternate Healthy Eating Index (AHEI), Diet Quality Index-Revised (DQIR), Recommended Food Score (RFS), and the alternate Mediterranean Diet Score (aMED), among 2,729 women from the Nurses' Health Study with invasive Stage 1-3 breast cancer diagnosed between 1978 and 1998 with follow-up through 2004. In multivariate adjusted analyses, no association was found between diet quality indices and either total or non-breast-cancer-related deaths. However, a higher aMED score was associated with a lower risk of non-breast-cancer death in women with low physical activity; the RR comparing the highest to lowest tertile was 0.39 (95% CI, 0.20-0.75, P trend = 0.0004). Our results suggest that a higher-quality diet after breast cancer diagnosis does not considerably change the risk of death from breast cancer. However, healthy dietary choices may be important because women are at risk of death from non-breast-cancer-related causes affected by diet.

PMID: 21462090

Breast Cancer Res Treat. 2013 Sep 17. [Epub ahead of print]

Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent girls, and risk for benign breast disease in young women.

Berkey CS, Willett WC, Tamimi RM, Rosner B, Frazier AL, Colditz GA.

Source

Channing Division of Network Medicine, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA, catherine.berkey@channing.harvard.edu.

Abstract

Previous investigations, of adolescent diet recalled in adulthood, found lower risk for benign breast disease (BBD) with higher intakes of vegetable fat and nuts during high school. We investigate whether vegetable protein and fat, derived from diets reported during pre-adolescence and adolescence, are associated with subsequent risk for BBD in young women. The Growing Up Today Study includes 9,039 females, 9-15 years in 1996, who completed questionnaires annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency questionnaires (1996-2001) obtained intake data on a variety of foods. Beginning in 2005, women (18-30 years) reported whether they had ever been diagnosed with BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression estimated associations between intakes of vegetable protein and fat and biopsy-confirmed BBD. Those individual foods that were the largest contributors of protein and fat in this cohort were also investigated. In analyses of intakes from 1996 through 1998, when our cohort was youngest, vegetable fat (OR = 0.72/(10 gm/day), 95 % CI 0.53-0.98; p = 0.04) was inversely associated with BBD risk. The greatest sources of vegetable fat and protein in these girls were peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A daily serving of any one of these was associated with lower risk (OR = 0.32/(serv/day), 95 % CI 0.13-0.79; p = 0.01). Peanut butter (and nuts) at age 11 years was inversely associated with risk (p = 0.01). In analyses of intakes at age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10 gm/day), 95 % CI 0.43-0.95; p = 0.03). A daily serving at 14 years of any one of the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16-0.75; p = 0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of breast cancer had significantly lower risk if they consumed these foods or vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut butter, or nuts by older girls may help reduce their risk of BBD as young women.

PMID: 24043428

Mol Carcinog. 2013 Sep 4. doi: 10.1002/mc.22074. [Epub ahead of print]

Dietary fat without body weight gain increases in vivo MCF-7 human breast cancer cell growth and decreases natural killer cell cytotoxicity.

Lamas B, Nachat-Kappes R, Goncalves-Mendes N, Mishellany F, Rossary A, Vasson MP, Farges MC.

Source

Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne, INRA, UMR 1019, Clermont-Ferrand, France.

Abstract

High-calorie (HC) diet contributes to the increased incidence of obesity, which is a risk factor for breast cancer in postmenopausal women, and in particular for estrogen receptor (ER) positive tumors. This study investigated whether an HC diet increases human ER-positive breast cancer progression and modulates natural killer (NK) cell functions. Four-week-old female BALB/c athymic nude mice were fed a HC diet (5320 kcal/kg) or standard calorie diet (SC, 2820 kcal/kg) for 6 mo. After 5 mo, the mice were randomly implanted with MCF-7 breast cancer cells (SCT and HCT) or received an isovolumic injection (SC and HC) in both inguinal fat pads. Tumor growth was greater in the HCT group than in the SC group without change in body weight. The HC diet decreased the tumor expression of genes involved in the citrate cycle and in adiponectin and lipid metabolism but increased that of genes controlling glycolysis and angiogenesis. The tumor expression level of Ki67 was increased while that of the cleaved caspase 3 and the ER-β and progesterone receptors was reduced. Tumor development in response to the HC diet was associated with smaller numbers and lower cytotoxicity of splenic NK cells. These results indicate that an HC diet without body weight gain increases ER-positive breast cancer cell proliferation and reduces tumor apoptosis. The underlying mechanisms might involve a downexpression of tumor hormonal receptor and reduced NK cell functions, and might also result in the regulation of genes involved in several cellular functions. © 2013 Wiley Periodicals, Inc.

© 2013 Wiley Periodicals, Inc.

KEYWORDS: 

NK cells, high-calorie diet, human breast carcinoma xenograft

PMID: 24038423

BMC Cancer. 2013 Sep 13;13(1):418. [Epub ahead of print]

Characterization of synergistic anti-cancer effects of docosahexaenoic acid and curcumin on DMBA-induced mammary tumorigenesis in mice.

Siddiqui RA, Harvey KA, Walker C, Altenburg J, Xu Z, Terry C, Camarillo I, Jones-Hall Y, Mariash C.

Abstract

BACKGROUND: 

The major obstacles to the successful use of individual nutritional compounds as preventive or therapeutic agents are their efficacy and bioavailability. One approach to overcoming this problem is to use combinations of nutrients to induce synergistic effects. The objective of this research was to investigate the synergistic effects of two dietary components: docosahexaenoic acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM), an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced mammary tumorigenesis in mice.

METHODS: 

We used the carcinogen DMBA to induce breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance and tumor progression were monitored daily. The tumors were harvested 15 days following their first appearance for morphological and immunohistological analysis. Western analysis was performed to determine expression of maspin and survivin in the tumor tissues. Characterization of tumor growth was analyzed using appropriate statistical methods. Otherwise all other results are reported as mean +/- SD and analyzed with one-way ANOVA and Tukey's post hoc procedure.

RESULTS: 

Analysis of gene microarray data indicates that combined treatment with DHA + CCM altered the profile of "PAM50" genes in the SK-BR-3 cell line from an ER-/Her-2+ to that resembling a "normal-like" phenotype. The in vivo studies demonstrated that DHA + CCM treatment reduced the incidence of breast tumors, delayed tumor initiation, and reduced progression of tumor growth. Dietary treatment had no effect on breast size development, but tumors from mice on a control diet (untreated) were less differentiated than tumors from mice fed CCM or DHA + CCM diets. The synergistic effects also led to increased expression of the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic protein, survivin.

CONCLUSIONS: 

The SK-BR-3 cells and DMBA-induced tumors, both with an ER- and Her-2+ phenotype, were affected by the synergistic interaction of DHA and CCM. This suggests that the specific breast cancer phenotype is an important factor for predicting efficacy of these nutraceuticals. The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon the molecular phenotype of the cancer.

PMID: 24034496

Br J Cancer. 2013 Sep 10. doi: 10.1038/bjc.2013.544. [Epub ahead of print]

The association between different night shiftwork factors and breast cancer: a case-control study.

Fritschi L, Erren TC, Glass DC, Girschik J, Thomson AK, Saunders C, Boyle T, El-Zaemey S, Rogers P, Peters S, Slevin T, D'Orsogna A, de Vocht F, Vermeulen R, Heyworth JS.

Source

Western Australian Institute for Medical Research, The University of Western Australia, Nedlands, Western Australia, Australia.

Abstract

Background:Research on the possible association between shiftwork and breast cancer is complicated because there are many different shiftwork factors, which might be involved including: light at night, phase shift, sleep disruption and changes in lifestyle factors while on shiftwork (diet, physical activity, alcohol intake and low sun exposure).Methods:We conducted a population-based case-control study in Western Australia from 2009 to 2011 with 1205 incident breast cancer cases and 1789 frequency age-matched controls. A self-administered questionnaire was used to collect demographic, reproductive, and lifestyle factors and lifetime occupational history and a telephone interview was used to obtain further details about the shiftwork factors listed above.Results:A small increase in risk was suggested for those ever doing the graveyard shift (work between midnight and 0500 hours) and breast cancer (odds ratio (OR)=1.16, 95% confidence interval (CI)=0.97-1.39). For phase shift, we found a 22% increase in breast cancer risk (OR=1.22, 95% CI=1.01-1.47) with a statistically significant dose-response relationship (P=0.04). For the other shiftwork factors, risks were marginally elevated and not statistically significant.Conclusion:We found some evidence that some of the factors involved in shiftwork may be associated with breast cancer but the ORs were low and there were inconsistencies in duration and dose-response relationships.British Journal of Cancer advance online publication, 10 September 2013; doi:10.1038/bjc.2013.544 www.bjcancer.com.

PMID: 24022188

Cancer Epidemiol Biomarkers Prev. 2013 Sep 9. [Epub ahead of print]

Equol producing status, isoflavone intake, and breast density in a sample of US Chinese women.

Tseng M, Byrne C, Kurzer MS, Fang CY.

Source

California Polytechnic State University.

Abstract

Background: Differences in ability to metabolize daidzein to equol might help explain inconsistent findings regarding isoflavones and breast cancer. We examined equol producing status in relation to breast density, a marker of breast cancer risk, and evaluated whether an association of isoflavone intake with breast density differs by equol producing status in a sample of Chinese immigrant women. Methods: Participants were 224 women, age 36-58 years, enrolled in a study on diet and breast density. All women completed dietary recall interviews, underwent a soy challenge to assess equol producing status, and received a mammogram assessed for breast density using a computer-assisted method. Results: In our sample, 30% were classified as equol producers. In adjusted linear regression models, equol producers had significantly lower mean dense tissue area (32.8 vs. 37.7 cm2, p=0.03) and lower mean percent breast density (32% vs. 35%, p=0.03) than non-producers. Significant, inverse associations of isoflavone intake with dense area and percent density were apparent, but only in equol producers (interaction p=0.05 for both). Conclusions: These results support the possibility that equol producing status affects breast density, and that effects of isoflavones on breast density depend on ability to metabolize daidzein to equol. Impact: While these findings warrant confirmation in a larger sample, they offer a possible explanation for the inconsistent findings regarding soy intake and breast density and possibly also breast cancer risk. The findings further suggest the importance of identifying factors that influence equol producing status, and exploring appropriate targeting of interventions.

PMID: 24019393

S-equol is produced by intestinal bacteria in some, but not in all, humans after soy consumption. The ability of S-equol to play a role in the treatment of estrogen or androgen-mediated diseases or disorders was first proposed in 1984

Cancer Sci. 2013 Aug 28. doi: 10.1111/cas.12268. [Epub ahead of print]

Lactobacillus casei Shirota enhances the preventive efficacy of soymilk in chemically induced breast cancer.

Kaga C, Takagi A, Kano M, Kado S, Kato I, Sakai M, Miyazaki K, Nanno M, Ishikawa F, Ohashi Y, Toi M.

Source

Yakult Central Institute for Microbiological Research, Tokyo, Japan.

Abstract

Soy foods are known to be effective for breast cancer prevention. The habitual consumption of soy isoflavones in combination with probiotic Lactobacillus casei Shirota (LcS) was shown to decrease the risk of breast cancer occurrence in our previous population-based case-controlled study among Japanese women. The present study aimed to elucidate the cooperative prevention mechanism of soymilk and LcS using an animal carcinogenic model. Female Sprague-Dawley rats received a high-fat, AIN-76A diet containing soymilk, LcS, both soymilk and LcS, or none and were orally exposed to 2-amino1-methyl-6-penylimidazo[4,5-b]pyridine at a dose of 85 mg/kg body weight 8 times for 2 weeks. The development of palpable mammary tumors was monitored for 17 weeks. Tumor tissues were immunohistochemically examined for estrogen receptor (ER)-α, Ki-67 and CD34. Compared with the control group, the incidence and the multiplicity of the mammary tumors were reduced by soymilk alone and soymilk in combination with LcS, while the tumor volume was decreased by LcS alone and LcS in combination with soymilk. An immunohistochemical analysis revealed that soymilk in combination with LcS more effectively reduced the numbers of ER-α-positive and Ki-67-positive cells in tumor than soymilk alone and that each soymilk and LcS inhibited the tumor angiogenesis. These results demonstrated that soymilk prevents the development of mammary tumors and that LcS suppresses tumor growth, potentially enhancing the preventive efficacy of soymilk. The habitual consumption of LcS in combination with soymilk might be a beneficial dietary style for breast cancer prevention. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID: 23992486

Oncol Rep. 2000 Sep-Oct;7(5):977-82.

The effect of an oral administration of Lactobacillus casei strain shirota on azoxymethane-induced colonic aberrant crypt foci and colon cancer in the rat.

Yamazaki K, Tsunoda A, Sibusawa M, Tsunoda Y, Kusano M, Fukuchi K, Yamanaka M, Kushima M, Nomoto K, Morotomi M.

Source

Second Department of Surgery, School of Medicine, Showa University, Shinagawa-ku, Tokyo 142-8666, Japan.

Abstract

The preventive effect of oral administration of viable Lactobacillus casei strain Shirota (LcS) on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) and colon cancers in the rat was investigated. The study consisted of two experiments; in a short-term experiment (Exp-I), the inhibitory effect of 8- and 12-week treatments with LcS. Forty rats each received weekly a subcutaneous injection of AOM at a dose of 15 mg/kg of body weight for 5 weeks. Eight and twelve weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon and the mesenteric lymph nodes (MLN) were removed. The number of ACFs and the surface marker of lymphocytes derived from the MLN were investigated. The large ACF (those comprising four or more aberrant crypts per focus) had significantly decreased in the rats which had consumed the LcS diet. And oral administration of viable LcS significantly recovered CD8 positive lymphocytes to the levels in the control group. In a long-term experiment (Exp-II), 30 rats each received weekly a subcutaneous injection of AOM at a dose of 7. 4 mg/kg of body weight for 10 weeks. Twenty-five weeks after the start of the carcinogen treatment, each subgroup of rats were sacrificed, and the colon were removed. The number and incidence of colon cancers were investigated. The number of rats with colon cancers and the number of colon cancers per rat, were significantly decreased in the rats which had consumed the LcS diet. LcS inhibited chemically-induced colon carcinogenesis in the rat. CD8 positive T lymphocytes may play a key role in the preventive effect against colon carcinogenesis.

PMID: 10948325

Clin Nutr. 2013 Aug 15. pii: S0261-5614(13)00206-9. doi: 10.1016/j.clnu.2013.08.001. [Epub ahead of print]

A comprehensive metabolic evaluation reveals impaired glucose metabolism and dyslipidemia in breast cancer patients early in the disease trajectory.

Bell KE, Di Sebastiano KM, Vance V, Hanning R, Mitchell A, Quadrilatero J, Russell C, Dubin JA, Bahl M, Califaretti N, Campbell C, Mourtzakis M.

Source

Department of Kinesiology, University of Waterloo, Burt Matthew Hall Rm. 1117, 200 University Avenue W., Waterloo, ON N2J 3G1, Canada.

Abstract

BACKGROUND & AIMS: 

Weight gain in breast cancer patients during treatment is prevalent; the metabolic implications of this weight gain are poorly understood. We aimed to characterize glucose metabolism in breast cancer patients near the initiation of chemotherapy.

METHODS: 

Stage I-II breast cancer patients (n = 8) were evaluated near the initiation of chemotherapy and compared with a group of age- and body mass index-matched, as well as a group of young healthy, non-malignant females. Fasting blood samples (analyzed for lipids and cytokines) were taken and an oral glucose tolerance test was performed. Body composition, waist circumference, diet, cardiovascular fitness and muscle strength were evaluated.

RESULTS: 

Breast cancer patients were abdominally obese (mean ± SD: 94.6 ± 14.0 cm), overweight (28.8 ± 6.0 kg/m2) and dyslipidemic (triacylglycerides: 1.84 ± 1.17 mM; high-density lipoprotein cholesterol: 1.08 ± 0.23 mM). Compared to non-malignant matched females, fasting glucose and insulin concentrations were similar but fasting c-peptide was greater in patients (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater extent in patients during the oral glucose tolerance test compared with all non-malignant females. During the glucose tolerance test, c-peptide, but not insulin, remained elevated in patients compared with all non-malignant females. No differences in body composition, serum cytokines, nutrition or exercise capacity between patients and matched, non-malignant females emerged.

CONCLUSIONS: 

Breast cancer patients present with unhealthy metabolic features early in the disease trajectory. Future investigations need to examine the underlying mechanisms and the potential longitudinal changes following chemotherapy.

Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

KEYWORDS: 

AUC, BMI, Body composition, CRP, Cytokines, DBP, EDTA, Exercise, HDL-c, IDF, IL, Insulin, International Diabetes Federation, LDL-c, NCEP-ATPIII, NEFA, National Cholesterol Education Program – Third Adult Treatment Panel, Nutrition, OGTT, PAQ, SBP, TAG, TNF-α, VO(2peak), area under the curve, body mass index, c-Peptide, c-reactive protein, diastolic blood pressure, ethylenediaminetetraacetic acid, high-density lipoprotein cholesterol, interleukin, low-density lipoprotein cholesterol, non-esterified fatty acid, oral glucose tolerance test, peak oxygen uptake, physical activity questionnaire, systolic blood pressure, triacylglycerol, tumor necrosis factor-α

PMID: 24011971

Int J Cancer. 2013 Aug 30. doi: 10.1002/ijc.28466. [Epub ahead of print]

Associations of dietary folate, vitamin B6, B12 and methionine intake with risk of breast cancer among African American (AA) and European American (EA) women.

Gong Z, Ambrosone CB, McCann SE, Zirpoli G, Chandran U, Hong CC, Bovbjerg DH, Jandorf L, Ciupak G, Pawlish K, Lu Q, Hwang H, Khoury T, Wiam B, Bandera EV.

Source

Department of Cancer Prevention & Control, Roswell Park Cancer Institute, Buffalo, NY.

Abstract

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl-group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case-control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (4th vs. 1st quartile: OR=0.57, 95% CI, 0.33-1.00; P for trend=0.06) and for ER positive tumors (4th vs. 1st quartile: OR=0.58, 95% CI, 0.36-0.93; P for trend=0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (4th vs. 1st quartile: OR=1.53, 95% CI, 1.06-2.21; P for trend=0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation. © 2013 Wiley Periodicals, Inc.

Copyright © 2013 UICC.

KEYWORDS: 

African American, European American, breast cancer, diet, folate, one-carbon nutrients

PMID: 23996837

Expert Opin Ther Targets. 2013 Sep 14. [Epub ahead of print]

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review.

Bizzarri M, Proietti S, Cucina A, Reiter RJ.

Source

University La Sapienza, Department of Experimental Medicine, Systems Biology Group , Rome , Italy mariano.bizzarri@uniroma1.it.

Abstract

Introduction: Compelling evidence has highlighted the complex pleiotropic functions elicited by the melatonin in cancer cells. Melatonin behaves as a 'smart killer', i.e., modulating anti-apoptotic processes in normal cells, and triggering pro-apoptotic signals in cancer cells. Areas covered: Melatonin induces programmed cell death in a wide range of different tumors (breast, gastro-intestinal, hematological, prostate, osteosarcoma, melanoma, kidney, etc…). Mechanisms of action and molecular pathways involved in pro-apoptotic processes under melatonin treatment are discussed. Expert opinion: Melatonin involvement in apoptotic processes is a new and relevant field of investigation. Even in tumor models unresponsive to melatonin alone, this hormone can significantly amplify the cytostatic and the cytotoxic effects triggered by other compounds or conventional drugs. We are far from having a satisfactory understanding about how and when melatonin exerts its beneficial effects. Melatonin in the nanomolar range activates the intrinsic and/or the extrinsic apoptotic pathway in cancer cells, namely through an increase in the p53/MDM2p ratio and downregulation of Sirt1. This finding is of great relevance since there is intense research ongoing to identify nontoxic feasible inhibitors of MDM2 and Sirt1. Melatonin should be evaluated for the management of those cancers where both of these are overexpressed and functionally strategic.

PMID: 24032643

J Pineal Res. 2013 Apr;54(3):334-45. doi: 10.1111/jpi.12032. Epub 2013 Jan 17.

Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

Jablonska K, Pula B, Zemla A, Owczarek T, Wojnar A, Rys J, Ambicka A, Podhorska-Okolow M, Ugorski M, Dziegiel P.

Source

Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.

Abstract

In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC.

© 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

PMID: 23330677

Summary: While it is common, there is no reason not to look at vitamin B levels and possibly turmeric to oppose worsening. Also think about elevated alkaline phosphatase, acetyl-carnitine, and even L-dopa.

J Neurol. 2013 May;260(5):1358-66. doi: 10.1007/s00415-012-6805-y. Epub 2012 Dec 28.

MR imaging and cognitive correlates of relapsing-remitting multiple sclerosis patients with cerebellar symptoms.

Cerasa A, Valentino P, Chiriaco C, Pirritano D, Nisticò R, Gioia CM, Trotta M, Del Giudice F, Tallarico T, Rocca F, Augimeri A, Bilotti G, Quattrone A.

Neuroimaging Research Unit, Institute of Neurological Sciences, National Research Council, 88100, Germaneto, CZ, Italy. a.cerasa@unicz.it

Abstract

Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system, frequently associated with cognitive impairments. Damages of the cerebellum are very common features of patients with MS, although the impact of this clinical factor is generally neglected. Recent evidence from our group demonstrated that MS patients with cerebellar damages are characterized by selective cognitive dysfunctions related to attention and language abilities. Here, we aimed at investigating the presence of neuroanatomical abnormalities in relapsing-remitting MS patients with (RR-MSc) and without (RR-MSnc) cerebellar signs. Twelve RR-MSc patients, 14 demographically, clinically, and radiologically, matched RR-MSnc patients and 20 controls were investigated. All patients underwent neuropsychological assessment. After refilling of FLAIR lesions on the 3D T1-weighted images, VBM was performed using SPM8 and DARTEL. A correlation analysis was performed between VBM results and neuropsychological variables characterizing RR-MSc patients. Despite a similar clinical status, RR-MSc patients were characterized by more severe cognitive damages in attention and language domains with respect to RR-MSnc and controls. With respect to controls, RR-MSnc patients were characterized by a specific atrophy of the bilateral thalami that became more widespread (including motor cortex) in the RR-MSc group (FWE < 0.05). However, consistent with their well-defined neuropsychological deficits, RR-MSc group showed atrophies in the prefrontal and temporal cortical areas when directly compared with RR-MSnc group. Our results demonstrated that RR-MS patients having cerebellar signs were characterized by a distinct neuroanatomical profile, mainly involving cortical regions underpinning executive functions and verbal fluency.

PMID: 23271221

Arch Neurol. 2012 Oct;69(10):1366-71. doi: 10.1001/archneurol.2012.2356.

Slowly progressive ataxia, neuropathy, and oculomotor dysfunction.

Jordan JT, Samuel G, Vernino S, Muppidi S.

Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Justin.Jordan@phhs.org

Abstract

A 54-year-old white man presented with slowly progressive incoordination and weakness. He had normal motor development until, at 16 years of age, he noted difficulty walking and difficulty reading despite normal visual acuity. By the fourth decade of life, he developed poor coordination and balance, as well as inability to walk. In subsequent years, he developed progressive, painless sensory loss, weakness, and atrophy in his distal arms and legs. His vision problems progressed and he also developed dysarthria without dysphagia. Family history was negative except for an uncle who was described as "clumsy." Results of an oculomotor examination were notable for increased square-wave jerks, persistent bilateral gaze-evoked nystagmus with saccadic pursuit, intact vestibulo-ocular reflex, and saccadic dysmetria. He had a mixed dysarthria with flaccid and ataxic characteristics and severe weakness and atrophy in the distal limb muscles. Sensation was diminished to the midforearms and midthighs in all modalities. Deep tendon reflexes were absent throughout, with no response to plantar stimulation. He had marked appendicular ataxia with mild axial ataxia. Magnetic resonance imaging of the brain revealed severe cerebellar atrophy. Results of an electrodiagnostic study suggested a severe axonal sensorimotor polyneuropathy with active and chronic denervation. The differential diagnosis in a patient with ataxia, neuropathy, and oculomotor features is discussed; a methodical approach to the diagnostic workup is suggested; and the final diagnosis is revealed.

PMID: 23044593

Child Adolesc Psychiatry Ment Health. 2012 Jun 22;6(1):25. doi: 10.1186/1753-2000-6-25.

Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report.

Tufan AE, Bilici R, Usta G, Erdoğan A.

Assistant Professor, Abant Izzet Baysal University Medical Faculty, Department of Child and Adolescent Psychiatry, Baysal, Turkey. tevrenus@yahoo.com.

Abstract

Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were "irritability, regressive behavior, apathy, crying and truancy" which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg's sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg's sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.

PMID: 22726236

BMJ Case Rep. 2013 Apr 22;2013. pii: bcr2013008906. doi: 10.1136/bcr-2013-008906.

A rare case of alcoholic pellagra encephalopathy with startle myoclonus and marked response to niacin therapy: time for a new dictum?

Sharma B, Sannegowda RB, Jain R, Dubey P, Prakash S.

Department of Neurology, SMS Medical College Hospital, Jaipur, Rajasthan, India. sharmadrbhawna@gmail.com

Abstract

We report a case of 56-year-old man, chronic alcoholic, presented to us with progressive weakness in all the four limbs with stiffness and gait disturbance since 1-year associated with cognitive impairment. On examination he had mild confusion, spastic quadriparesis with brisk reflexes, extensor plantars and cerebellar features. During the hospital stay myoclonus was noticed in the patient, which was startle in nature. He did not have dermatitis, ascites or any stigmata of liver failure. MRI of brain revealed bilateral subdural effusion, left focal subarachnoid haemorrhage at perisylvian area and diffuse cortical atrophy. He was treated with supportive measures including thiamine with which his condition worsened. His serum niacin was low. With a possibility of alcoholic pellagra encephalopathy (APE) the patient was treated with niacin. His clinical condition improved drastically over next 1 week and startle myoclonus disappeared, favouring the diagnosis of APE though multiple confounding factors were present.

PMID: 23608853

Brain Dev. 2011 Oct;33(9):790-5. doi: 10.1016/j.braindev.2011.06.001. Epub 2011 Jul 20.

Epilepsy in children with methylmalonic acidemia: electroclinical features and prognosis.

Ma X, Zhang Y, Yang Y, Liu X, Yang Z, Bao X, Qin J, Wu X.

Department of Pediatrics, Peking University First Hospital, Beijing, PR China.

Abstract

OBJECTIVE: 

To summarize the electroclinical features and prognosis of epilepsy in children with methylmalonic acidemia (MMA).

METHODS: 

The medical records of hospitalized MMA patients associated with epilepsy were retrospectively reviewed. The clinical manifestations, laboratory examination results, and treatment modalities were analyzed.

RESULTS: 

From 63 pediatric inpatients diagnosed as MMA in Peking University First Hospital from June 1996 to December 2009, 27 children (42.9%) associated with epilepsy were enrolled in this study. These 27 patients were also accompanied with other neurological manifestations including mental retardation or regression (n=22), lethargy (n=10), increased muscle tone (n=8), muscle hypotonia (n=8), recurrent vomiting (n=4), tremor (n=2), ataxia (n=2), and abnormal posture (n=1).The onset age of seizure ranged from 8 days to 11 years. The seizure types included partial seizure (n=21), generalized tonic-clonic seizure (n=5), tonic seizure (n=3), myoclonic seizure (n=3), and epileptic spasms (n=2). Five patients had two or three seizure types. Nine patients (33.3%) had a history of status epilepticus. EEG showed slow background activity in 17 patients, focal or multifocal paroxysmal discharges in 16 patients, generalized paroxysmal discharges in four patients, hypsarrythmia in two patients, and suppression-burst pattern in one patient. Cranial MRI scans showed bilateral cerebral atrophy (n=14), increased T2 signal intensities in white matter (n=12), agenesis of corpus callosum (n=2), bilateral increased T2 signal intensities or necrosis in basal ganglia (n=2), and cerebellar atrophy (n=1). Twenty one patients were MMA combined with homocysteinemia. Seventeen patients were confirmed with cobalamin C disease and one with partial mutase deficiency (mut(-)). Vitamin B12-responsive patients had a better outcome compared with vitamin B12-unresponsive patients.

CONCLUSIONS: 

Epilepsy is a common manifestation of patients with MMA. Partial seizure is more common than other seizure types. Urine organic acid analysis should be performed for children with unknown cause of epilepsy combined with other neurological manifestations, so as to promptly identify the etiology and improve the prognosis.

Copyright © 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

PMID: 21764232

Neuropsychopharmacology. 2007 Oct;32(10):2229-37. Epub 2007 Feb 14.

Cerebellar gray matter volume correlates with duration of cocaine use in cocaine-dependent subjects.

Sim ME, Lyoo IK, Streeter CC, Covell J, Sarid-Segal O, Ciraulo DA, Kim MJ, Kaufman MJ, Yurgelun-Todd DA, Renshaw PF.

Source

Department of Psychiatry, Seoul National University College of Medicine, Seoul 110-744, South Korea.

Abstract

This study was conducted to explore differences in gray and white matter volume between cocaine-dependent and healthy comparison subjects using optimized voxel-based morphometry (VBM). Brain magnetic resonance imaging (MRI) and neuropsychological function tests were performed for 40 cocaine-dependent subjects (41.4+/-6.9 years, 27 men) and 41 healthy age- and sex-matched comparison subjects (38.7+/-8.8 years, 26 men). Optimally normalized whole brain MR images were segmented, modulated, smoothed, and compared between groups with statistical parametric mapping. The cocaine-dependent group had lower gray matter volumes in bilateral premotor cortex (Brodmann area (BA) 6, 8; 16.6%), right orbitofrontal cortex (BA 10, 15.1%), bilateral temporal cortex (BA 20, 38; 15.9%), left thalamus (12.6%), and bilateral cerebellum (13.4%) as well as lower right cerebellar white matter volume (10.0%) relative to the comparison group at a corrected p<0.05 for multiple comparisons. Duration of cocaine use negatively correlated with right and left cerebellar gray matter volumes (r=-0.37, r=-0.39, respectively). In cocaine-dependent subjects, lower cerebellar hemispheric gray and white matter volumes were correlated with deficits in executive function and decreased motor performance. This study reports that cocaine-dependent subjects have lower gray matter volumes in cerebellar hemispheres as well as in frontal, temporal cortex, and thalamus. These findings are the first to suggest that the cerebellum may be vulnerable to cocaine-associated brain volume changes, and that cerebellar deficits may contribute to neuropsychological deficits and motor dysfunction frequently observed in cocaine-dependent subjects.

PMID: 17299505

Cocaine blocks norepinephrine, serotonin, dopamine, and other neurotransmitters from being reabsorbed.

Tohoku J Exp Med. 2007 Jan;211(1):95-6; author reply 97.

Cerebral folate deficiency and folinic acid treatment in hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) syndrome.

Mercimek-Mahmutoglu S, Stockler-Ipsiroglu S.

Comment on

Effective treatment with levodopa and carbidopa for hypomyelination with atrophy of the basal ganglia and cerebellum. [Tohoku J Exp Med. 2006]

PMID: 17202777

Tohoku J Exp Med. 2006 Jun;209(2):163-7.

Effective treatment with levodopa and carbidopa for hypomyelination with atrophy of the basal ganglia and cerebellum.

Wakusawa K, Haginoya K, Kitamura T, Togashi N, Ishitobi M, Yokoyama H, Higano S, Onuma A, Nara T, Iinuma K.

Department of Pediatrics, Tohoku University School of Medicine, 1-1 Seiryomachi, Sendai 980-8574, Japan. k-wakusawa@nifty.com

Abstract

Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare leukoencephalopathy presenting in the infantile period and characterized by diffuse cerebral hypomyelination, and atrophy of the basal ganglia and cerebellum. As patients with H-ABC lack remarkable laboratory findings, the diagnosis is based on brain magnetic resonance imaging findings alone. Only eight cases have been reported in the literature, and thus the natural course and treatment of this disease are not fully understood. We report a 35-month-old boy with H-ABC who had hemidystonia, hypomyelination, and cerebellar ataxia. We diagnosed H-ABC after considering a thorough differential diagnosis, excluding other diseases involving hemidystonia, hypomyelination, and cerebellar ataxia. Furthermore, technetium-99m ethyl cysteinate dimmer-single-photon emission computerized tomography (Tc-ECD-SPECT) and positron emission tomography with fluorodeoxyglucose (18)F (FDG-PET) revealed decreased blood flow and glucose metabolism in the bilateral lenticular nucleus, thalamus, and cerebellum. A peroral levodopa preparation containing carbidopa (levodopa-carbidopa) was effective at ameliorating and stopping the progression of the patient's dystonia (final effective doses: levodopa, 200 mg/day and carbidopa, 20 mg/day). This is the first case report of a Japanese patient with H-ABC and treatment for this disease. Levodopa-carbidopa may be an effective treatment for H-ABC.

Rinsho Shinkeigaku. 1990 Nov;30(11):1232-7.

[A case of membranous lipodystrophy (Nasu) with diffuse cerebral white matter involvement and cerebellar atrophy on brain CT and MRI].

[Article in Japanese]

Shibata K, Uchiyama S, Takeuchi M, Kobayashi I, Maruyama S.

Source

Department of Neurology, Tokyo Women's Medical College.

Abstract

A 37-year-old female was admitted to our hospital because of progressive dementia and gait disturbance. She was healthy until 34 years of age when she had difficulty in walking and memory disturbance with personality changes. At age 36, she developed urinary incontinence and dementia. The neurological examination demonstrated euphoric mental state, emotional incontinence, severe dementia, paraplegia, dysmetria, choreic movements in both arms and urinary incontinence. Diffuse hyperreflexia and bilateral Babinski signs were observed. Routine laboratory examination showed slightly increased erythrocyte sedimentation rate and alkaline phosphatase. Electroencephalogram revealed diffuse irregular slow waves. X-ray film of the ulnar bone revealed osteoporotic and cystic lesions. The biopsy of the left tibial bone showed a specific membranous cystic structure. Computerized tomography (CT) of the brain showed symmetric, diffuse low density areas in the cerebral white matter and severe atrophy of the cerebellum. T2-weighted magnetic resonance imaging (MRI) revealed diffuse high intensity areas in the cerebral white matter. The present case is characterized by diffuse changes in cerebral white matter and cerebellar atrophy, which have been never reported in Nasu-Hakola disease. The diffuse cerebral white matter changes shown by CT and MRI appear to indicate that this patient is the first case of leukodystrophy of sudanophilic type since the original case reported by Nasu et al.

PMID: 2085928

Int J Mol Epidemiol Genet. 2011;2(2):114-21. Epub 2011 Feb 10.

Plasma alkaline phosphatase is elevated in Alzheimer's disease and inversely correlates with cognitive function.

Kellett KA, Williams J, Vardy ER, Smith AD, Hooper NM.

Abstract

Alkaline phosphatase is present on neuronal membranes and plasma alkaline phosphatase activity increases in brain injury and cerebrovascular disease, suggesting that plasma alkaline phosphatase may partly reflect neuronal loss. As neuronal loss occurs in Alzheimer's disease (AD), we hypothesised that alterations in plasma alkaline phosphatase activity may correlate with cognitive impairment. Plasma alkaline phosphatase activity was measured in the longitudinal Oxford Project to Investigate Memory and Aging (OPTIMA) cohort (121 AD patients, 89 mild cognitive impairment (MCI) patients and 180 control subjects). Plasma alkaline phosphatase activity was significantly higher in the AD patients relative to the controls (p<0.001). In the MCI patients, plasma alkaline phosphatase was at a level in between that seen in control and AD subjects, consistent with the clinical status of this group. Furthermore, plasma alkaline phosphatase activity inversely correlated with cognitive function (assessed by the Cambridge Examination for Mental Disorders (CAMC0G)) in controls (z= -2.21 p=0.027), MCI (z= -2.49, p=0.013) and AD patients (z= -3.61, p=0.0003). These data indicate that plasma alkaline phosphatase activity is increased in AD and inversely correlates with cognitive function regardless of diagnostic status.

KEYWORDS: 

Alkaline phosphatase, Alzheimer's, cognitive function, mild cognitive impairment, plasma

PMID: 21686125

J Physiol Biochem. 2011 Dec;67(4):519-30. doi: 10.1007/s13105-011-0097-z. Epub 2011 May 27.

Acetyl-L-carnitine prevents carbon tetrachloride-induced oxidative stress in various tissues of Wistar rats.

Annadurai T, Vigneshwari S, Thirukumaran R, Thomas PA, Geraldine P.

Source

Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, 620 024, Tamil Nadu, India.

Abstract

Acetyl-L-carnitine (ALCAR) has been shown to prevent experimental selenite cataractogenesis, a manifestation of oxidative stress, but little is known about its potential in other settings of oxidative stress. The present study was based on the hypothesis that ALCAR prevents carbon tetrachloride (CCl(4))-induced oxidative stress in vital tissues. Male albino Wistar rats were divided into three groups, each of six rats. Group I (control) rats received only vehicle (1 ml/kg b.w.) for 4 days; Group II (CCl(4)-exposed, untreated) rats received CCl(4) (2 ml/kg b.w.) on the second and third days and vehicle on the first and fourth days; Group III (CCl(4)-exposed, ALCAR-treated) rats received ALCAR (200 mg/kg b.w.) for 4 days and CCl(4) on the second and third days. All administrations were made intraperitoneally. After the experimental period, significantly (P < 0.05) elevated mean serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase were observed in Group II rats when compared to Group I and Group III rats. The mean levels of vitamin C, vitamin E, and reduced glutathione and the mean activities of superoxide dismutase, catalase, and glutathione peroxidase were significantly (P < 0.05) lower in samples of hemolysate and of liver, kidney, and brain tissues of Group II rats than those in Group I and Group III rats. The mean level of lipid peroxidation was significantly (P < 0.05) higher in Group II rats than that in Group I and Group III rats. Moreover, the CCl(4)-induced upregulation of inducible nitric oxide synthase expression was prevented by ALCAR in the liver and brain tissues. These results suggest that ALCAR is able to prevent the CCl(4)-induced oxidative stress.

PMID: 21618017

Food Chem Toxicol. 2010 Nov;48(11):3246-61. doi: 10.1016/j.fct.2010.08.034. Epub 2010 Sep 4.

Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.

Yousef MI, Omar SA, El-Guendi MI, Abdelmegid LA.

Source

Department of Environmental Studies, Institute of Graduate Studies and Research, Alexandria University, Alexandria, Egypt. yousefmokhtar@yahoo.com

Abstract

The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20804811

Toxicol Ind Health. 2011 Nov;27(10):923-33. doi: 10.1177/0748233711399324. Epub 2011 Apr 21.

Protective effect of chrysin on carbon tetrachloride (CCl4)-induced tissue injury in male Wistar rats.

Anand KV, Anandhi R, Pakkiyaraj M, Geraldine P.

Source

Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.

Abstract

Chrysin, a natural flavonoid has been reported to possess potent anti-inflammatory, anti-cancer and antioxidation properties. In the present study, we aimed to evaluate the putative protective effect of chrysin, an isoflavone, on carbon tetrachloride (CCl(4))-induced toxicity in male Wistar rats. Intraperitoneal administration of CCl(4) (2 ml/kg) to rats for 4 days resulted in significantly elevated (p < 0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), when compared to normal rats. In addition, the tissues (liver, kidney and brain) and haemolysate samples showed considerable increase in levels (p < 0.05) of malondialdehyde (MDA) and lowered levels (p < 0.05) of reduced glutathione (GSH), vitamin C and E when compared to values in normal rats. Quantitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) exhibited lower activities of these antioxidant enzymes in the tissues and haemolysate of CCl(4)-administered rats. The protective action of chrysin on CCl(4)-induced rat was demonstrated with SGPT, SGOT, ALP and LDH resuming to near normal levels, while the mean levels of GSH and of vitamin C and E were elevated, the mean activities of CAT, SOD and Gpx were enhanced and the mean level of MDA was lowered in the tissue and haemolysate samples when compared to the CCl(4)-exposed untreated rats. The expression of the iNOS gene appeared to be up-regulated in the liver and kidney samples of CCl(4)-exposed untreated rats, whereas in CCl(4)-exposed chrysin-treated rats, the mRNA transcript levels of iNOS approximated normal levels. These results strongly suggest that chrysin is able to prevent the oxidative damage induced by CCl(4) in the liver, brain, kidney and haemolysate of male Wistar rats.

PMID: 21511893 Passion flower.

World J Biol Psychiatry. 2008;9(3):231-5.

Serum markers of brain-cell damage and C-reactive protein are unaffected by electroconvulsive therapy.

Giltay EJ, Kho KH, Blansjaar BA.

GGZ Delfland, Institute of Mental Health, Delft, The Netherlands. giltay@dds.nl

Abstract

The effects of electroconvulsive therapy (ECT) on serum levels of the acute-phase reactant C-reactive protein (CRP) and intracellular enzymes such as alkaline phosphatase (ALP), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatine kinase (CK), have received little attention. If brain cells are damaged, CK-BB, LDH and AST levels are expected to show (minor) elevations. We measured serum levels of prolactin, AST, ALT, LDH, ALP, CK and CRP before and 5 min, 30 min, 4 h, 1 day, 2 days, and 3 days after ECT in 15 consecutive patients (eight women and seven men; mean 53.9 years old, range 3082) who did not receive ECT in the preceding 2 weeks. Prolactin levels increased (P = 0.001), but none of the other mean concentrations significantly increased over time. All concentrations remained within the normal range in every patient, except for five samples with elevated CK levels (range 333-675 IU/l). CK-MB and CK-BB fractions, however, remained low, indicating that skeletal muscle was the source of the CK elevation. Serum levels of markers of brain cell leakage and inflammation remained low following one ECT session, suggesting that ECT does not cause direct brain cell leakage, nor an inflammatory response.

PMID: 17853285

Nat Genet. 1995 Sep;11(1):45-51.

Mice lacking tissue non-specific alkaline phosphatase die from seizures due to defective metabolism of vitamin B-6.

Waymire KG, Mahuren JD, Jaje JM, Guilarte TR, Coburn SP, MacGregor GR.

Department of Genetics and Molecular Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

In humans, deficiency of the tissue non-specific alkaline phosphatase (TNAP) gene is associated with defective skeletal mineralization. In contrast, mice lacking TNAP generated by homologous recombination using embryonic stem (ES) cells have normal skeletal development. However, at approximately two weeks after birth, homozygous mutant mice develop seizures which are subsequently fatal. Defective metabolism of pyridoxal 5'-phosphate (PLP), characterized by elevated serum PLP levels, results in reduced levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. The mutant seizure phenotype can be rescued by the administration of pyridoxal and a semi-solid diet. Rescued animals subsequently develop defective dentition. This study reveals essential physiological functions of TNAP in the mouse.

PMID: 7550313 [

Summary: continuing hormonal imbalances can worsen symptoms and addressing those imbalances may improve them.

Pak J Biol Sci. 2011 Apr 1;14(7):433-40.

Growth hormone deficiency in children and adolescents with cerebral palsy: relation to gross motor function and degree of spasticity.

Hamza RT, Ismail MA, Hamed AI.

Source

Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Abstract

Children with Cerebral Palsy (CP) often have poor linear growth during childhood with short final height. Thus, we aimed to assess serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels among CP patients and their relation to each of gross motor function and degree of spasticity. Fifty CP children and adolescents were studied in comparison to 50 healthy age-, sex- and pubertal stage-matched children and adolescents. All subjects were subjected to clinical evaluation, Intelligence Quotient (IQ) assessment and measurement of serum GH, IGF-1 and IGFBP-3. All auxological and hormonal parameters were significantly lower among cases. Fifty two% of cases were GH-deficient and 62% had reduced IGF-land IGFBP-3 levels. Gross Motor Function Measure- 88 (GMFM-88) score correlated negatively with each of basal (r = -0.71, p = 0.02) and peak stimulated GH (r =-0.88, p = <0.001); IGF-1 (r = -0.64, p = 0.04) and IGFBP-3 (r = -0.69, p = 0.031). There were significant negative correlations between the degree of spasticity assessed by Modified Ashworth Scale and each of basal (r = -0.61, p = 0.032) and peak stimulated GH (r = -0.78, p = 0.01); IGF-1 (r = -0.65, p = 0.041) and IGFBP-3 (r = -0.62, p = 0.035). Growth Hormone Deficiency (GHD) is prevalent in children with CP and could be one of the causes of their short stature.

PMID: 21902055

Dev Med Child Neurol. 2011 Oct;53(10):933-7. doi: 10.1111/j.1469-8749.2011.04045.x.

The motor repertoire of extremely low-birthweight infants at term in relation to their neurological outcome.

DE Vries N, Bos A.

Source

Department of Paediatrics, Leeuwarden Medical Centre, Leeuwarden Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands.

Abstract

Aim The aim of this study was to assess the motor repertoire of extremely low-birthweight infants at term-equivalent age (TEA), in relation to their neurological outcome. Method Using Prechtl's method, we assessed both the quality of general movements and a detailed motor optimality score in 13 extremely low-birthweight infants (four males; nine females; mean gestational age 27.9wks, SD 2.9wks; mean birthweight 798g, SD 129g) at TEA, and related them to general movements at the age of 3 months after term and neurological outcome at the age of 2 years 6 months. Results At TEA, 10 of the 13 infants had abnormal general movements. All infants showed abnormal leg lifting with extended legs; nine showed stiff movements, three showed cramped movements, and two showed cramped synchronized general movements. At 3 months, three infants still had abnormal general movements. Concurrent movements were abnormal in nine infants owing to monotony and jerkiness. Abnormal posture was seen in seven infants. None developed cerebral palsy; one infant showed cognitive and motor delay. Neurological outcome was not related to general movement quality and optimality score at TEA. Interpretation Abnormal general movements at TEA are common in extremely low-birthweight infants. General movements often appear stiff and cramped with extended legs. At the age of 3 months after term, general movements are mostly normal, but concurrent movements are not. Nevertheless, these abnormalities do not imply an impaired neurological outcome such as cerebral palsy.

© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.

PMID: 21896004

Ugeskr Laeger. 2011 Mar 28;173(13):962-5.

[Evidence exists for prophylactic magnesium sulphate as a neuroprotector in premature births].

[Article in Danish]

Wolf HT, Hegaard HK, Huusom L, Greisen G, Hedegaard M.

Source

Medicinsk Afdeling, Nykøbing Falster Sygehus, 4800 Nykøbing Falster, Denmark. trapwolf@hotmail.com

Abstract

Preterm birth increases the child's risk of cerebral palsy. Observational studies as well as randomized studies find that magnesium sulphate given to women in preterm birth decreases such risk. A Cochrane meta-analysis of the randomized studies shows no change in mortality, whereas some observational studies find a mortality decrease. It is important to identify the neuroprotective mechanism and to decide whether these results are relevant in the current Danish obstetrical practice. Should we use magnesium sulphate now or should questions about doses, time of administration and maternal side effects be answered first?

PMID: 21453636

Ann Trop Paediatr. 2010;30(3):181-96.

A review of the incidence and prevalence, types and aetiology of childhood cerebral palsy in resource-poor settings.

Gladstone M.

Source

Department of Community Child Health, Alder Hey Children's NHS Foundation Trust, Liverpool, UK. mgladstone@btinternet.com

Abstract

BACKGROUND: 

With 80% of children with disabilities living in resource-poor settings, it is likely that there is a high prevalence of cerebral palsy (CP) and neurological impairment in these settings. The prevalence and incidence rates of disability, in particular of children with CP in resource-poor settings, are difficult to access and clarify.

AIM: 

To review the recent literature relating to the prevalence, incidence, type and aetiology of cerebral palsy in low-income settings.

METHODS: 

A systematic search of studies published between 1990 and 2009 was performed using PubMed, Cinahl on Ovid, the Cochrane database, SCOPUS and information from international disability organisations. All studies with information about neurodisability, CP or disability in resource-poor settings were included. Titles and/or abstracts of all studies were reviewed and full texts of relevant studies were obtained.

RESULTS: 

Disparities in methodology, age range, classification systems and populations made studies difficult to compare. Population-based studies provided rates of childhood disability of 31-160/1000. When using limited age ranges of 2-9 years with the Ten Question Questionnaire, rates were 82-160/1000 for children disability and 19-61/1000 for neurological impairment. Rates of CP in population-based settings in China and India gave figures of 2-2.8/1000 births, similar to western settings. Hospital-based studies of CP showed increased rates of spastic quadriplegia rather than diplegia or hemiplegia and possibly increased rates of meningitis, jaundice and asphyxia and lower rates of low birthweight and prematurity in CP populations. These studies were small and not case-controlled or population-based.

CONCLUSIONS: 

Rates of CP and neurological impairment are difficult to obtain in resource-poor settings. Methods of identifying children with CP and causal factors and the effects of disability need to be better classified in order to improve management and help shape preventive measures.

PMID: 20828451 

Ther Clin Risk Manag. 2011;7:199-206. Epub 2011 May 30.

Effects of recombinant growth hormone (GH) replacement and psychomotor and cognitive stimulation in the neurodevelopment of GH-deficient (GHD) children with cerebral palsy: a pilot study.

Devesa J, Alonso B, Casteleiro N, Couto P, Castañón B, Zas E, Reimunde P.

Source

Medical Center "Proyecto Foltra", Cacheiras (Teo), A Coruña, Spain;

Abstract

Cerebral palsy (CP) is the main cause of physical disability in childhood and is an important health issue that has a strong socioeconomic impact. There is no effective treatment for CP and therapeutic approaches report only partial benefits for affected people. In this study we assessed the effects of growth hormone (GH) treatment combined with psychomotor and cognitive stimulation in the neurodevelopment of children with CP and GH deficiency (GHD). The study was carried out in 11 patients (7 boys and 4 girls; 4.12 ± 1.31 years) with GHD and CP who were treated with recombinant GH (rGH) and psychomotor and cognitive stimulation during 2 months. Battelle Developmental Inventory Screening Test (BDIST) was performed 2 months before commencing GH treatment, just before commencing GH administration, and after 2 months of combined treatment involving GH and cognitive stimulation. Psychomotor and cognitive status did not change during the period in which only cognitive stimulation was performed; however, significant improvements in personal and social skills, adaptive behavior, gross motor skills and total psychomotor abilities, receptive and total communication, cognitive skills and in the total score of the test (P < 0.01), and in fine motor skills and expressive communication (P < 0.02) were observed after the combined treatment period. Therefore, GH replacement together with psychomotor and cognitive stimulation seem to be useful for the appropriate neurodevelopment of children with GHD and CP.

PMID: 21691590

Summary: Despite largely being ignored, chronic Epstein-Barr is recognized as life threatening. But we don't have a middle diagnosis, hindering treatment.

Adolesc Med State Art Rev. 2012 Aug;23(2):277-84.

An adolescent evaluated for chronic fatigue: does she have a sleep disorder?

Gonzalez M1, Fisher M.

Author information

Abstract

A 13-year-old girl presented to our Division of Adolescent Medicine for evaluation of ongoing fatigue. She and her mother reported that 15 months earlier, when the patient was in the 7th grade, she started to be tired and "sleep all the time." They do not remember her being ill at that time; a test for mononucleosis was reportedly positive, but Epstein-Barr virus titers showed "old disease." She remained fatigued throughout 7th grade but attended school without falling asleep; however, she was too tired to do her work and had to attend summer school. The patient received home instruction in 8th grade and reported that on weekdays she slept from 1 AM to 11 AM with a nap from 4 to 8 PM and on weekends she slept from 3 AM to 1 PM without a nap.

PMID: 23162932

Zhonghua Er Ke Za Zhi. 2009 Sep;47(9):682-6.

[Clinical characteristics and follow-up of 12 cases with severe chronic active Epstein-Barr virus infection].

[Article in Chinese]

Song HM1, Wu XY, Wang W, Xing Y, Li F, Qiu JJ, Xiao J, Wei M.

Author information

Abstract

OBJECTIVE:

There are two different types of chronic active Epstein-Barr virus (CAEBV) infection: chronic EBV (CEBV) having persistent infectious mononucleosis (IM)-like illness with relatively good prognosis, and severe CAEBV (SCAEBV)infection that has rather severe manifestations and generally poor prognosis with many life-threatening complications, such as EBV-associated malignant lymphoma and hemophagocytic syndrome (HPS). The purpose of this study was to clarify the clinical and prognostic characteristics in 12 cases with SCAEBV infection.

METHOD:

Data of 12 cases with SCAEBV infection were analyzed retrospectively, which included clinical and auxiliary examination, pathological data, especially EB virus (EBV)-antibodies and DNA in peripheral blood mononuclear cells (PBMC) and infected tissue, and follow-up information.

RESULT:

Of the 12 cases, 7 were male and 5 were female. The age at the onset of diseases ranged from 35 months to 14 years (median, 11 years). The major manifestations were fever (100%), splenomegaly (91.7%), hepatomegaly (83.3%), lymphadenopathy (75.0%), and others, including skin rash, development retardation, jaundice, ascites, pulmonary hypertension, oral ulcer, cholecystitis and pleural effusion. The abnormalities of auxiliary examination were as follows: elevated LDH level (91.7%), liver dysfunction (83.3%), anemia (75.0%), leukopenia (58.3%), neutropenia (50.0%), thrombocytopenia (25.0%) and abnormal chest X-ray findings. At the time of onset, 58.3% of the patients had an IM-like illness. In all of the 12 cases, EBV serologic tests revealed high IgG antibody levels against EB viral capsid antigen (VCA). The patients often had positive IgM and IgA antibodies against VCA (33.3% and 66.7%) as well. Elevated IgG antibody level to early antigen (EA) (100.0%), occasionally positive IgA antibody (40.0%) were also seen. The mean load of EBV-DNA detected by real-time polymerase chain reaction (PCR) in the PBMC was (8.12 x 10(6), median)copies/ml. Four of 12 cases presented a poor clinical course, two of whom died from EBV-associated HPS, 1 from severe multiple pathogens infection, and 1 from multiple organ failure. In addition, 1 case developed Hodgkin's T cell lymphoma and another case showed hepatopulmonary syndrome in 2 years after splenectomy.

CONCLUSIONS:

The clinical feature of SCAEBV infection varied exceedingly. EBV-DNA load in PBMC of SCAEBV infected patients was significantly increased. More attention should be paid to the disease because of its severe complications, poor prognosis and high mortality.

PMID: 20021792

Am J Gastroenterol. 1986 Sep;81(9):808-11.

Exudative ascites complicating infectious mononucleosis.

Marano AR, Lanse SB, Garsten JJ, Thornton GF, Antopol SC, Gannon D.

Abstract

A case of Epstein-Barr virus mononucleosis with the unusual complication of exudative ascites is presented. The patient was a 22-yr-old man with the typical symptoms and physical findings of hepatitis secondary to infectious mononucleosis. Extensive evaluation including liver biopsy, failed to show another cause for the patient's ascites. The ascites and hepatitis disappeared with resolution of the acute mononucleosis infection. He is well 12 months after this illness with no evidence for chronic liver disease. This case adds to the list of causes for exudative ascites associated with acute hepatitis.

PMID: 375204

Wiad Lek. 2009;62(4):235-42.

[Chronic active Epstein-Barr virus infection in an adult].

[Article in Polish]

Kościelak J.

Author information

Abstract

A chronic active Epstein-Barr virus infection (CAEBV) following infectious mononucleosis in a 58 years old woman is reported. The disease lasted for one year, and in spite of an intensive search for its cause, was diagnosed only at the 8th months since its onset. A low frequency of CAEBV in caucasians and patient's age were likely responsible for the belated diagnosis. The disease presented with a high, intermittent fever, general lymphoadenopathy, splenomegalia, hypoalbuminemia, polyclonal gamma globulinemia and malaise. Starting from the 6th month, i.e. before the diagnosis was established, a high dose oral therapy with methylprednisolone was introduced. The improvement was significant but the disease recurred after drug withdrawal. Nevertheless its course was milder. At the 8th month since the disease onset elevated antibody to viral capsid antigen (VCA) together with antibody to early antigen (EA) and nuclear antigen (EBNA) were still found in patient's blood. DNA of EBV was detected by PCR in patient's blood and saliva. The patient recovered completely after one year, and as of today i.e. June 2009, is feeling well. A likely cause of the successful steroid therapy is discussed. A review part of the article describes etiopathogenesis, complications, occurrence and treatment of CAEBV, as well as its relation to various lymphoproliferation disorders.

PMID: 20648766

Curr Treat Options Neurol. 2012 Oct;14(5):464-73. doi: 10.1007/s11940-012-0189-2.

Sleep dysfunction in multiple system atrophy.

Ferini-Strambi L1, Marelli S.

Author information

Abstract

OPINION STATEMENT:

Sleep disorders in multiple system atrophy (MSA) are common manifestation and include reduced and fragmented sleep, excessive daytime sleepiness, REM sleep behaviour disorder (RBD), and sleep-disordered breathing. Of these, RBD is the most common (affecting 90 %-100 % of patients with MSA) and is regarded as a red flag for MSA. RBD, as well as stridor during sleep, may be the initial manifestation of the disease, occurring several years before the waking motor and dysautonomic onset. Sleep disorders occur in both MSA with predominant parkinsonism (MSA-P) and MSA with predominant cerebellar ataxia (MSA-C). Treatment strategies in patients with MSA presenting difficulties in initiating and maintaining sleep need to be highly individualized. Clonazepam has been found to be successful in treating RBD symptoms at the dose of 0.25 to 2.0 mg given approximately 30 min before bedtime. In case of comorbid obstructive sleep apnea, zopiclone (at the dose from 3.75 to 7.5 mg each night) or melatonin (with a recommended dose of 3 to 12 mg at bedtime) may be alternative treatments. An increased survival in MSA patients with stridor may be obtained both with continuous positive airway pressure (CPAP) and tracheostomy. Since tracheostomy is an invasive surgical procedure, not easily accepted by the patient, CPAP therapy should be considered first. However, tracheostomy is first indicated when stridor is present during wakefulness because of the high risk of respiratory failure and death. In MSA, obstructive sleep apnea (OSA) occurs more frequently than central sleep apnea, ranging from 15 % to 37 % of the cases. CPAP is an effective treatment for eliminating obstructive sleep apnea in MSA patients, even if the adaptation to the device may be difficult in advanced cases.

PMID: 22886854

Summary: Despite being treated as an ongoing tolerable infection, C. difficile can kill monkeys injected with the toxin.

I seem to be in much demand this week, but I thought I would take a moment to compile a bit of follow up information for you. For my favorite bug, I'm including a study on its uses against Clostridium diarrhea. The brand I use is SBC from Douglas Labs that I get wholesale from Emerson Ecologics 18006544432 (Now Fullscript on my home page). As a practitioner you should be able to get it wholesale, and/or generate it fresh in large batches through making Kombucha tea.

PLoS One. 2011;6(6):e20944. Epub 2011 Jun 9.

Prebiotic effects of wheat arabinoxylan related to the increase in bifidobacteria, Roseburia and Bacteroides/Prevotella in diet-induced obese mice.

Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, Cani PD, Larondelle Y, Delzenne NM.

Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium.

Abstract

BACKGROUND: 

Alterations in the composition of gut microbiota--known as dysbiosis--has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice.

METHODOLOGY/PRINCIPAL FINDINGS: 

Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters.

CONCLUSIONS/SIGNIFICANCE: 

Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention.

PMID: 21695273

MGN-3 500mg DOUBLE STRENGTH BioBran Arabinoxylan Compound AHCC (50 Vegetarian Capsules) by Lane Labs (MGN3 MGN 3) Brand: Daiwa Health Development ($148) rice fiber bran with enzymes. 

Interdiscip Perspect Infect Dis. 2008;2008:829101. Epub 2008 Dec 3.

Insights into the roles of gut microbes in obesity.

Sanz Y, Santacruz A, De Palma G.

Institute of Agrochemistry and Food Technology (IATA), Spanish National Research Council (CSIC), P.O. Box 73, Burjassot, 46100 Valencia, Spain.

Abstract

Obesity is a major public health issue as it enhances the risk of suffering several chronic diseases of increasing prevalence. Obesity results from an imbalance between energy intake and expenditure, associated with a chronic low-grade inflammation. Gut microbes are considered to contribute to body weight regulation and related disorders by influencing metabolic and immune host functions. The gut microbiota as a whole improves the host's ability to extract and store energy from the diet leading to body weight gain, while specific commensal microbes seem to exert beneficial effects on bile salt, lipoprotein, and cholesterol metabolism. The gut microbiota and some probiotics also regulate immune functions, protecting the host form infections and chronic inflammation. In contrast, dysbiosis and endotoxaemia may be inflammatory factors responsible for developing insulin resistance and body weight gain. In the light of the link between the gut microbiota, metabolism, and immunity, the use of dietary strategies to modulate microbiota composition is likely to be effective in controlling metabolic disorders. Although so far only a few preclinical and clinical trials have demonstrated the effects of specific gut microbes and prebiotics on biological markers of these disorders, the findings indicate that advances in this field could be of value in the struggle against obesity and its associated-metabolic disorders.

PMID: 19259329 

J Pediatr. 1984 Jan;104(1):34-40.

Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: physiologic and pathologic basis.

Arnon SS, Mills DC, Day PA, Henrickson RV, Sullivan NM, Wilkins TD.

Abstract

Clostridium botulinum can colonize and produce botulinal toxin in the human infant intestine, which the toxin then permeates to cause generalized flaccid paralysis, and occasionally, sudden death. This study was undertaken to test the hypothesis that toxins produced by other intestinal clostridia, e.g., C. difficile, might also cause systemic illness and sometimes death in infants (J Pediatr 100:568, 1982). Because this hypothesis could not be evaluated clinically until the systemic manifestations of C. difficile toxins in primates were known, infant rhesus monkeys were given 6 to 11 micrograms/kg of the recently purified C. difficile toxins A or B, either intravenously or intraperitoneally. The animals showed no abnormalities for several hours, but then developed lethargy, hypotonia, hypothermia, and, shortly before death, sudden elevation of serum concentrations of potassium, magnesium, and phosphorus and of enzymes that derived mainly from skeletal muscle, heart and brain. Five of six animals died quietly 3.5 to 8.0 hours after onset of symptoms. Death appeared to result from cessation of breathing, after which the sinus tachycardia then deteriorated to a flat ECG. Necropsy findings were insufficient to explain the cause of death. It appears that in infant monkeys microgram amounts of C. difficile toxins A and B can produce a rapid quiet death, the cause of which is undetectable at necropsy, a situation pathologically reminiscent of crib death in human infants, although the possible clinical identity of these two conditions has yet to be established.

PMID: 6690674

Infect Immun. 1999 Jan;67(1):302-7.

Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa.

Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C.

Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Saccharomyces boulardii is a nonpathogenic yeast used in the treatment of Clostridium difficile diarrhea and colitis. We have reported that S. boulardii inhibits C. difficile toxin A enteritis in rats by releasing a 54-kDa protease which digests the toxin A molecule and its brush border membrane (BBM) receptor (I. Castagliuolo, J. T. LaMont, S. T. Nikulasson, and C. Pothoulakis, Infect. Immun. 64:5225-5232, 1996). The aim of this study was to further evaluate the role of S. boulardii protease in preventing C. difficile toxin A enteritis in rat ileum and determine whether it protects human colonic mucosa from C. difficile toxins. A polyclonal rabbit antiserum raised against purified S. boulardii serine protease inhibited by 73% the proteolytic activity present in S. boulardii conditioned medium in vitro. The anti-protease immunoglobulin G (IgG) prevented the action of S. boulardii on toxin A-induced intestinal secretion and mucosal permeability to [3H]mannitol in rat ileal loops, while control rabbit IgG had no effect. The anti-protease IgG also prevented the effects of S. boulardii protease on digestion of toxins A and B and on binding of [3H]toxin A and [3H]toxin B to purified human colonic BBM. Purified S. boulardii protease reversed toxin A- and toxin B-induced inhibition of protein synthesis in human colonic (HT-29) cells. Furthermore, toxin A- and B-induced drops in transepithelial resistance in human colonic mucosa mounted in Ussing chambers were reversed by 60 and 68%, respectively, by preexposing the toxins to S. boulardii protease. We conclude that the protective effects of S. boulardii on C. difficile-induced inflammatory diarrhea in humans are due, at least in part, to proteolytic digestion of toxin A and B molecules by a secreted protease.

PMID: 9864230

The common medical flu prevention is: wash your hands, sneeze into your sleeve, and get the flu shot. Here is an individualized flu prevention program I made up for a patient. Each program is individualized, but the idea is that there is a lot more you can do.

1) Good food

Mediterranean diet

No fast food

Avoid junk, sugar

2) Stress relief

Meditate

Shield yourself from bad bugs and bad people

Practice saying no

Cultivate your spirit

4) Sleep

Sleep in cycles 1.5 hours

Nap 20 minutes a day

Relax between crises

5) Immune support

Avoid deficiencies in vitamins, zinc, selenium

Take a good multivitamin based on smell and taste

Take quantities of antioxidants as possible: colored fruits and vegetables, juices

Tai Chi, Qi Gong, breathing exercises 2 to 4 minutes a day

Stretching One minute every hour of work

Speaking Up and asking for what you need: accept rejection rather than assuming it.

Feeling rather than stuffing: channel your emotions into creative solutions

6) Immune blasters

Antibiotics: Save until last resort.

Kitchen spices: all volatile oils are somewhat bacteriostatic and antiviral

Garlic: kills everything that amoxicillin kills except pseudomonas (green mucus)

Alcohol based tinctures: toxic sludge / any alcohol use requires probiotic replacement

Immune cell boosters: Echinacea, mushroom mixes

Antivirals: licorice, lemon balm for viruses

Liver support: dark green leafy vegetables

Partial fasting (only vegetable stews)

Teas (based on taste)

Probiotics (REUT3, using SBC as a backup) (Emerson codes, call 1 800 654-4432)

Gentle laxatives: magnesium (muscle ache? Possible resolution, vitamin C (flu aid)

7) Moving the body

Castor/Olive oil packs (over liver, abdomen)

Lymph drainage massage (gentle rolling down to the throat from the ears)

Inversion (put your legs above your heart one minute every hour)

Yoga

Lymph gland specific massage (any sore gland should shrink with gentle massage)

Visualization of movement

8) Animal/herbal complexes to support immune function

Thymus/thyroid/adrenal

Alternatively eating intuitively

Astragalus/Sambucol/Berberine (EHB, SAMB8 from Emerson)

9) Creative protection

Visualize flu leaving the body, immune system moving it out

Generate a family ritual for ridding the house of bad bugs

As part of the family ritual, wash and remove shoes before entering

Wash commonly used surfaces with probiotics regularly. (SBC)

10) Conventional interventions

There is a time and a place for antibiotics

Decongestants can be antivirals: eucalyptus and menthol

NASAL INHALATION

1. You need: a large bowl, a large towel, 1 tsp cinnamon, cloves, ginger or turmeric. 2 quarts water, 1 box tissues.

2. Boil water, pour into the bowl. Add 1 tsp of your preferred spice. (Do Not over add, because these volatile oils can cause chemical burns. My personal failed experiment involved ½ cup of cinnamon).

3. Place towel over bowl. In placing your face under the towel, make sure that you leave sufficient cold air coming in the sides to avoid any burns. DO NOT BURN YOURSELF. If a burning sensation occurs, it will usually begin with the lips.

4. The goal of the treatment is to be able to inhale deeply, bringing the steam and spice to the lungs and up into the sinuses. When this begins to work, the sinuses will be begin to run freely. Blow very gently and wipe away mucus, continuing three rounds of one minute each under the towel. Repeat multiple times during an acute episode.

WARMING SOCKS TREATMENT

Warming socks are hydrotherapy (water healing). Using this treatment will help stimulate the immune system and relieve head congestion. As such, warming socks are often recommended for use during colds, flus, sore throats, ear infections, headaches, nasal congestion, coughs, bronchitis, and sinus infections. The warming socks treatment is best if repeated for at least three nights in a row.

Procedure

1. It is imperative that before you begin this treatment that your feet are warm. This is very important as the treatment will not be as effective and could be harmful (think hypothermia). Warming can be accomplished by soaking in warm water for 5-10 minutes.

2. Next, take a pair of cotton socks and wet the bottom with cold water. Be sure to wring the socks out thoroughly. (At this point, I soak the socks in icy water all the way up to the ankle, but I tend to run very hot.)

3. Place the cold wet socks on your feet. Cover with thick wool socks. Go to bed. Avoid getting chilled.

You will find that the wet cotton socks will be dry in the morning. Many patients report that they sleep much better during the treatment. In the case of a fever, I also wear a ski hat to bed to maintain body temperature. If I am experiencing head congestion, it is better not to wear the hat.

Nasal Lavage Instructions

Many people have chronic infections behind the nose, which are typically known as sinusitis, hayfever, or allergies. When you have a low-grade infection, there is a tendency to use up the body’s natural cortisone. This may result in an increased susceptibility to many kinds of infections.

The goal of the nasal lavage program is to reduce the chronic infection so the body can heal itself. Frequently antibiotics are not able to resolve these infections but the long-term use of the nasal lavage may prove extremely beneficial.

It is very important to follow all the instructions very carefully. Continue the routine until all symptoms resolve. This may take 3 to 6 months. BE PATIENT. For acute problems, perform the nasal wash up to four times per day until resolved. For chronic problems, it is usual to do the wash one or more times daily, continuing for several months.

Pain or bleeding after rinsing may mean that an infection is still present and so it is important to ask your doctor if you should continue with the program. Be persistent as it takes a lot of effort to rid your body of these chronic bacteria that may be producing the low-grade infection.

Supplies:

* Salt - sea salt is best * Filtered or bottled water

* Container or bulb syringe * Towel or washcloth

Directions: The technique, outlined below, may seem unusual at first. However, once learned, you will quickly realize how beneficial it is for sinus problems.

1. Locate a workable container. The pot pictured is specially designed with a spout that fits comfortably in one nostril. Alternatives you can use include a bulb syringe, a small flower watering pot, a turkey baster, or just a teacup (though the latter will be messier).

2. Fill the container with lukewarm salt water. The salt-to-water ratio is 1 teaspoon sea salt to 1 pint (2 cups) water. Filtered or bottled water is best.

3. Have some tissues within reach for this next part. Over a sink, tilt your head forward so that you are looking directly down toward the sink. Insert the spout into your right nostril. It is important that you breathe through your mouth. Turn your head to the right and let water move into the right nostril and exit the left nostril. Normally, you will feel the water as it passes through your sinuses. It is fine is some of the water drains into the mouth. Simply spit it out and adjust the tilt of your head.

4. After using a cup of water, repeat the above procedure for the other nostril.

5. To finish, expel any remaining water by quickly blowing air out both open nostrils 15 times over the sink. Avoid the temptation to block off one nostril, as doing so may force water into the eustachian tube.

For starting a fever, you can’t beat:

HOT FOMENTATION TREATMENT

Hot fomentations increase circulation and decrease chest congestion. They are a great treatments for a variety of acute conditions including bronchitis, coughs, chest colds, influenza, asthma, gallstones, dysmenorrhea and insomnia.

Contraindications: Do not use hot fomentations over areas of decreased/absent sensation, hemorrhage, gastric ulcers, malignancy, peripheral vascular disease, conditions aggravated by extreme cold.

Caution: Speak to your physician regarding changes in treatment for patients with asthma or other conditions that are induced or made worse by cold applications.

Supplies:

2 Wool Blankets (polyester if wool unavailable, but not cotton)

3 Washcloths in a bowl of ice water

1 Sheet

6 Medium hand or face towels

Hot water bottle

2 basins - one for hot (near boiling) water and the other for cold (ice) water (alternately the wet towels can be warmed in the microwave, cheating but somewhat less messy).

Pillow

Preparation

1. Spread 2 blankets lengthwise on a bed and cover with a sheet

2. Place the two water filled basins and the hot water bottle nearby. Put two towels in the hot basin and a washcloth in the cold.

Procedure

1. The person to be treated should disrobe down to their underwear and lie on their back atop

the blanket and sheet. Place the hot water bottle at their feet. Wrap the patient tightly with the blankets leaving the chest free.

2. Wring out 2 towels in hot water and apply them to the chest/abdomen. Wrap sheet and blanket tightly around the whole body "mummy-style". DO NOT BURN THE PATIENT. It is advisable to test the towel on the patient's arm prior to placing on the chest.

3. Place a cold wash cloth on the patient's forehead and place two more towels in the hot water

4. After three minutes, remove the towels from the chest and replace them with two fresh hot ones.

5. After three more minutes, remove the second set of towels. Have the patient sit up, and briskly rub the patient's back and chest for 30 seconds with one of the cold washcloths.

6. Repeat the process one last time (for a total of three cycles). After the last round of hot towels are removed, apply the cold friction to the whole body starting with the hands and arms, chest and back, then the legs and feet. Dip the washcloth into the cold water frequently during the friction rub.

7. Dry the patient and bundle warmly. Have them rest for at least 10 minutes or go to bed. If they are fighting an acute infection, this may help them to spike a fever and start the healing process.

I was stunned to read in 2011 that no alternative medicine treatments had any effect on colic. But the review (Ernst, April Pediatrics Journal) itself showed that out of fifteen trials “eleven trials indicated a significant result in favor of complementary and alternative medicines.” The reviewers’ commentary, not the facts, was taken out of context. A previous Pediatrics review (2000) found alternative medicine had: “some effective therapies for infant colic.”

In looking through the medical literature, breast feeding is superior to formula feeding in terms of the softening stool. Prebiotics caused more diarrhea and rashes. Probiotics were helpful in five studies. In a trial for cramping, Spascupreel was comparable to hyoscine butylbromide. When compared to the drug, the homeopathic Sprascupreel is nontoxic. One of its ingredients is chamomile. 

The biggest factor confirmed in colic is reactivity to diet. Older studies have shown a direct relationship to cow’s milk, with elimination of symptoms in the majority of infants. Other studies have found significant benefit only in those infants shown to be allergic. Using soy formula does not show significant benefit, possibly because soy is another common allergen. 

Parents should keep journals of symptoms and consult with their pediatricians. Colic can often be lessened by addressing lifestyle and dietary choices within the family. Simply waiting for the children to grow up is a prescription for grey hair. 

We begin with the “negative” review: 

Nutritional Supplements and Other Complementary Medicines for Infantile Colic: A Systematic Review

Rachel Perry, MPhil, MA, BAa, Katherine Hunt, PhD, MSc, BN, RNa, Edzard Ernst, PhD, MD, FMedSci, FSB, FRCPa 

aDepartment of Complementary Medicine, Peninsula Medical School, Universities of Exeter and Plymouth, Plymouth, United Kingdom 

Background Complementary and alternative medicines often are advocated for infantile colic, yet there has been no synthesis of the evidence to inform current practice about their use. 

Objective To critically evaluate all randomized clinical trials of nutritional supplements and other complementary and alternative medicines as a treatment for infantile colic. 

Methods Five electronic databases were searched from their inception to February 2010 to identify all relevant randomized clinical trials of complementary and alternative medicines and supplements for infantile colic. Reference lists of retrieved articles were hand searched. Data were extracted by two independent reviewers, and methodological quality was assessed using the Jadad score and key aspects of the Cochrane risk of bias. 

Results Fifteen randomized clinical trials met the inclusion criteria and were included. Thirteen studies were placebo controlled. Eight were of good methodological quality. Eleven trials indicated a significant result in favor of complementary and alternative medicines. However, none of these randomized clinical trials were without flaws. Independent replications were missing for most modalities. 

Conclusions Some encouraging results exist for fennel extract, mixed herbal tea, and sugar solutions, although it has to be stressed that all trials have major limitations. Thus, the notion that any form of complementary and alternative medicine is effective for infantile colic currently is not supported from the evidence from the included randomized clinical trials. Additional replications are needed before firm conclusions can be drawn. 

PEDIATRICS Vol. 106 No. 1 Supplement July 2000, pp. 184-190 

EARLY CHILDHOOD: COLIC, CHILD DEVELOPMENT, AND POISONING PREVENTION:

A Systematic Review of Treatments for Infant Colic 

Received Oct 25, 1999; accepted Feb 10, 2000. 

Michelle M. Garrison* and Dimitri A. Christakis*, 

From the * Child Health Institute, University of Washington; and Department of Pediatrics, University of Washington, Seattle, Washington. 

Objective: To conduct a systematic review of rigorously evaluated treatments for infant colic. 

Methods. Online bibliographic databases were searched for the term "colic" in articles classified as clinical trials or randomized controlled trials and conducted in infants. Reference lists from review articles, meta-analyses, and the selected articles were also reviewed for potential studies. The abstracts or full-text articles of 57 relevant studies were examined, of which 22 met the selection criteria. The methodology and findings of all retrieved articles were critically evaluated. Data were extracted from each article regarding study methods, intervention studied, outcomes measured, and results. 

Results. Four of the interventions studied had data of adequate quality and statistically significant numbers needed to treat (NNT): hypoallergenic diet (NNT = 6), soy formula (NNT = 2), reduced stimulation (NNT = 2), and herbal tea (NNT = 3). 

Conclusions. There are some effective therapies for infant colic, but additional rigorous studies of existing and alternative therapies are needed.

Lactobacillus reuteri DSM 17938 in Infantile Colic: A Randomized, Double-Blind, Placebo-Controlled Trial

Francesco Savino, MD, PhDa, Lisa Cordisco, PhDb, Valentina Tarasco, MDa, Elisabetta Palumeri, MDa, Roberto Calabrese, BSca, Roberto Oggero, MDa, Stefan Roos, PhDc, Diego Matteuzzi, PhDb 

a Department of Pediatrics, Regina Margherita Children Hospital, University of Turin, Turin, Italy; 

b Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy; and 

c Department of Microbiology, Swedish University of Agricultural Sciences, Uppsala, Sweden 

OBJECTIVE To test the efficacy of Lactobacillus reuteri on infantile colic and to evaluate its relationship to the gut microbiota. 

STUDY DESIGN Fifty exclusively breastfed colicky infants, diagnosed according to modified Wessel's criteria, were randomly assigned to receive either L reuteri DSM 17 938 (108 colony-forming units) or placebo daily for 21 days. Parental questionnaires monitored daily crying time and adverse effects. Stool samples were collected for microbiologic analysis. 

RESULTS Forty-six infants (L reuteri group: 25; placebo group: 21) completed the trial. Daily crying times in minutes/day (median [interquartile range]) were 370 (120) vs 300 (150) (P = .127) on day 0 and 35.0 (85) vs 90.0 (148) (P = .022) on day 21, in the L reuteri and placebo groups, respectively. Responders (50% reduction in crying time from baseline) were significantly higher in the L reuteri group versus placebo group on days 7 (20 vs 8; P = .006), 14 (24 vs 13; P = .007), and 21 (24 vs 15; P = .036). During the study, there was a significant increase in fecal lactobacilli (P = .002) and a reduction in fecal Escherichia coli and ammonia in the L reuteri group only (P = .001). There were no differences in weight gain, stooling frequency, or incidence of constipation or regurgitation between groups, and no adverse events related to the supplementation were observed. 

CONCLUSION L. reuteri DSM 17 938 at a dose of 108 colony-forming units per day in early breastfed infants improved symptoms of infantile colic and was well tolerated and safe. Gut microbiota changes induced by the probiotic could be involved in the observed clinical improvement. 

J Fam Health Care. 2010;20(6):206-9.

Infantile colic: practicalities of management, including dietary aspects.

Shergill-Bonner R.

Great Ormond Street Hospital, London.

Abstract

The incidence of infantile colic is between 5-20%. It occurs equally in breast- and bottle-fed infants, and in both sexes. The aetiology is unknown. The elimination of cow's milk protein and using extensively hydrolysed protein formula have been shown to be effective treatments for infantile colic. Partially hydrolysed milk has also been shown to be helpful and can be a useful option in the community when a cow's milk allergy is not considered to be an underlining cause of the colic. If symptoms persist the situation should be reassessed, as further investigations and treatment may be necessary. Certain behavioural interventions, such as reassurance, making changes to the parents' responsiveness to the infant, using motion/sound to calm the infant and reducing stimuli to the infant have also been shown to be effective treatments for infantile colic. There is some evidence to suggest that the use of prebiotic oligosaccharides, to restore normal healthy gut flora, can be beneficial. Soya milk is not recommended as a treatment.

PMID: 21319674

Asia Pac J Clin Nutr. 2010;19(4):473-80.

Effect of a whey-predominant starter formula containing LCPUFAs and oligosaccharides (FOS/GOS) on gastrointestinal comfort in infants.

Vivatvakin B, Mahayosnond A, Theamboonlers A, Steenhout PG, Conus NJ.

Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. BOOSBA.V@CHULA.AC.TH

Abstract

Development of new infant formulas aims to replicate the benefits of breast milk. One benefit of breast milk over infant formulas is greater gastrointestinal comfort. We compared indicators of gastrointestinal comfort in infants fed a whey-predominant formula containing long-chain polyunsaturated fatty acids, galacto-oligo-saccharides and fructo-oligosaccharides, and infants fed a control casein-predominant formula without additional ingredients. The single-centre, prospective, double-blind, controlled trial randomly assigned healthy, full-term infants (n=144) to receive exclusively either experimental or control formula from 30 days to 4 months of age. A group of exclusively breast-fed infants served as reference (n=80). At 1, 2, 3, and 4 months, infants' growth parameters were measured and their health assessed. Parents recorded frequency and physical characteristics of infants' stool, frequency of regurgitation, vomiting, crying and colic. At 2-months, gastric emptying (ultrasound) and intestinal transit time (H2 breath test) were measured, and stool samples collected for bacterial analysis. Compared to the control (n=69), fewer of the experimental group (n=67) had hard stools (0.7 vs 7.5%, p<0.001) and more had soft stools (90.8 vs 82.3%, p<0.05). Also compared to the control, the experimental group's stool microbiota composition (mean % bifidobacteria: 78.1 (experimental, n=17), 63.7 (control, n=16), 74.3 (breast-fed, n=20), gastric transit times (59.6 (experimental, n=53), 61.4 (control, n=62), 55.9 (breast-fed, n=67) minutes) and intestinal transit times (data not shown) were closer to that of the breast-fed group. Growth parameter values were similar for all groups. The data suggest that, in infants, the prebiotic-containing whey-based formula provides superior gastrointestinal comfort than a control formula.

PMID: 21147707

J Pediatr Gastroenterol Nutr. 2007 Mar;44(3):359-64.

Term infants fed formula supplemented with selected blends of prebiotics grow normally and have soft stools similar to those reported for breast-fed infants.

Ziegler E, Vanderhoof JA, Petschow B, Mitmesser SH, Stolz SI, Harris CL, Berseth CL.

Department of Pediatrics, University of Iowa Hospital and Clinic, Iowa City, IA, USA.

Abstract

OBJECTIVES: The present study was designed to evaluate the effect of 2 different combinations of prebiotic ingredients, polydextrose (PDX), galactooligosaccharides (GOS), and lactulose (LOS), at 2 different intake levels on the overall growth and tolerance in healthy term infants up to 120 days of age.

PATIENTS AND METHODS: Healthy, formula-fed, term infants (n = 226) were randomly assigned to 1 of 3 study formula groups: control group (n = 76), PG4 group (control formula supplemented with 4 g/L of a prebiotic blend, n = 74), or PGL8 group (control formula supplemented with 8 g/L of a prebiotic blend, n = 76). Anthropometric measurements were taken at 14, 30, 60, 90, and 120 days of age, and 24-hour dietary recall and 24-hour tolerance recall were recorded at 30, 60, 90, and 120 days of age. Adverse events were recorded throughout the study.

RESULTS: There were no statistically significant differences among the 3 formula groups for weight growth rate or length growth rate at any time point. Significant differences in stool consistency were detected among the 3 formula groups at 30, 60, and 90 days of age (P < 0.001, P = 0.025, P = 0.004, respectively), with the supplemented formula groups having looser stools than the control group. The PGL8 group had significantly higher stool frequency compared with the control and PG4 groups at 30 days of age (P = 0.021 and P = 0.017, respectively), but all of the groups were similar at 60, 90, and 120 days of age. A statistical difference was detected among the formula groups in 3 categories of adverse events: diarrhea (control vs PG4, 4% vs 18%, P = 0.008), eczema (PG4 vs control, 18% vs 7%, P = 0.046; PG4 vs PGL8, 18% vs 4%, P = 0.008), and irritability (control vs PGL8, 4% vs 16%, P = 0.027).

CONCLUSIONS: Infants fed formula supplemented with a prebiotic mixture achieved normal growth and stool characteristics more similar to those of breast-fed infants in comparison with infants fed an unsupplemented formula. A pediatrician needs to consider the risk of possible intolerance against the benefits of prebiotics.

PMID: 17325558

Appl Environ Microbiol. 2009 Feb;75(4):1121-8. Epub 2008 Dec 16.

Molecular ecological analysis of fecal bacterial populations from term infants fed formula supplemented with selected blends of prebiotics.

Nakamura N, Gaskins HR, Collier CT, Nava GM, Rai D, Petschow B, Russell WM, Harris C, Mackie RI, Wampler JL, Walker DC.

Division of Nutritional Sciences, Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 1207 W. Gregory Drive, Urbana, IL 61801, USA. nnakamur@illinois.edu

Abstract

Supplementation of infant formulas with prebiotic ingredients continues the effort to mimic functional properties of human milk. In this double-blind, controlled, 28-day study, healthy term infants received control formula (control group; n = 25) or control formula supplemented with polydextrose (PDX) and galactooligosaccharide (GOS) (4 g/liter) (PG4 group; n = 27) or with PDX, GOS, and lactulose (LOS) (either 4 g/liter [PGL4 group; n = 27] or 8 g/liter [PGL8 group; n = 25]). A parallel breast-fed group (BF group) (n = 30) was included. Stool characteristics, formula tolerance, and adverse events were monitored. Fecal bacterial subpopulations were evaluated by culture-based selective enumeration (Enterobacteriaceae), quantitative real-time PCR (Clostridium clusters I, XI, and XIV, Lactobacillus, and Bifidobacterium), and fluorescence in situ hybridization (FISH) (Bifidobacterium). Fecal bacterial community profiles were examined by using 16S rRNA gene PCR-denaturing gradient gel electrophoresis. The daily stool consistency was significantly softer or looser in the BF group than in all of the groups that received formula. The formulas were well tolerated, and the incidences of adverse events did not differ among feeding groups. Few significant changes in bacterial subpopulations were observed at any time point. The bacterial communities were stable; individual profiles tended to cluster by subject rather than by group. Post hoc analysis, however, demonstrated that the bacterial community profiles for subjects in the BF, PG4, PGL4, and PGL8 groups that first received formula at a younger age were less stable than the profiles for subjects in the same groups that received formula at an older age, but there was no difference for the control group. These data indicate that formulas containing PDX, GOS, and LOS blends are more likely to influence gut microbes when administration is begun in early infancy and justify further investigation of the age-related effects of these blends on fecal microbiota.

PMID: 19088307

Ann Saudi Med. 2010 Nov-Dec;30(6):468-70.

Predictive value of the cow's milk skin prick test in infantile colic.

Moravej H, Imanieh MH, Kashef S, Handjani F, Eghterdari F.

Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran. hmoravej@sums.ac.ir

Abstract

BACKGROUND AND OBJECTIVES: Infantile colic is a common problem among young infants. Cow's milk allergy has been suggested as one of the causes. We aimed to investigate the value of the cow's milk skin test for the diagnosis of cow's milk allergy in exclusively breast-fed infants with infantile colic.

METHODS: Exclusively breast-fed infants with infantile colic were enrolled in this study. On the first visit, the average hours of crying of the infant in a 24-h period were recorded and the cow's milk skin test was performed. If the infant had a positive skin test, elimination of cow's milk from the mothers' diet was advised. Infants with negative skin tests were divided into case and control groups. Cow's milk was eliminated from the diet of mothers in the case group. After 2 weeks, the number of hours of crying were recorded again. The reduction in the crying hours was compared between the two groups using the chi-square test.

RESULTS: Skin tests were positive in 3 of 114 cases (2.6%) of infantile colic. All three cases recovered completely following elimination of cow's milk from the mother's diet. Among the 111 patients with negative skin tests, 77 patients completed the study: 35 in the case group and 42 in the control group. The reduction in crying hours in infants in the case group was not significantly different from that in the control group.

CONCLUSION: Elimination of cow's milk from the mothers' diet is not beneficial for infants with a negative skin test. Infants with a positive skin test may benefit from this management.

PMID: 21060160

Pediatrics. 1983 Feb;71(2):268-71.

Cow's milk proteins cause infantile colic in breast-fed infants: a double-blind crossover study.

Jakobsson I, Lindberg T.

Abstract

Sixty-six mothers of 66 breast-fed infants with infantile colic were put on a diet free from cow's milk. The colic disappeared in 35 infants; it reappeared on at least two challenges (cow's milk to mother) in 23 infants (35%). A double-blind crossover trial with cow's milk whey protein was performed in 16 of these 23 mothers and infants. Six infants had to be taken out of the study for various reasons; of the remaining ten infants, nine reacted with colic after their mothers' intake of whey protein-containing capsules. Sequential analysis showed a high correlation between infantile colic in breast-fed infants and their mothers' consumption of cow's milk protein. A diet free of cow's milk is suggested for the mothers as a first trial of treatment of infantile colic in breast-fed infants.

PMID: 6823433

Pediatrics. 1989 Feb;83(2):262-6.

Cow's milk whey protein elicits symptoms of infantile colic in colicky formula-fed infants: a double-blind crossover study.

Lothe L, Lindberg T.

Department of Pediatrics, University of Lund, Malmö General Hospital, Sweden.

Erratum in:

Pediatrics 1989 Jul;84(1):17. 

Comment in:

Pediatrics. 1989 Nov;84(5):938-9. 

Abstract

There are several causes of infantile colic. The aim of this study was to evaluate, under controlled conditions, whether bovine whey proteins can elicit symptoms of infantile colic in colicky formula-fed infants. The mean age for entering the study was 6.4 weeks and the mean age for colic debut was 3.7 weeks. In 24 of 27 infants with severe colic, the symptoms disappeared when they were given a cow's milk-free diet (Nutramigen). These 24 infants were entered into a double-blind crossover study. The infants (receiving cow's milk-free diet) were given the contents of identical capsules with each meal during day 6. The same procedure was repeated on day 10. The capsules contained either whey protein powder (with Nutramigen added) or human albumin powder (with Nutramigen added). Eighteen infants receiving the whey protein-containing capsules reacted with colic, two infants receiving placebo reacted with colic (P less than .001), and four infants did not react at all. Crying hours per day for the 24 infants were 5.6 hours for formula-fed infants and 0.7 hour for cow's milk-free diet-fed infants (P less than .001). Crying hours per day were 3.2 hours for the infants receiving whey protein capsules and 1.0 hour for those receiving placebo (P less than .001). In conclusion, bovine whey protein can elicit symptoms of infantile colic in colicky formula-fed infants.

PMID: 2913556

Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003664.

Formulas containing hydrolysed protein for prevention of allergy and food intolerance in infants.

Osborn DA, Sinn J.

Westmead Hospital, Neonatal Unit, Hawkesbury Road, Westmead, New South Wales, Australia.

Update of:

Cochrane Database Syst Rev. 2003;(4):CD003664. 

Abstract

BACKGROUND: Allergies and food reactions are common and may be associated with foods including adapted cow's milk formula. Formulas containing hydrolysed proteins have been used to treat infants with allergy or food intolerance. However, it is unclear whether hydrolysed formula can be advocated for prevention of allergy and food intolerance in infants without evidence of allergy or food intolerance.

OBJECTIVES: To determine the effect of feeding hydrolysed formulas on allergy and food intolerance in infants and children compared to adapted cow's milk or human breast milk. If hydrolysed formulas are effective, to determine what type of hydrolysed formula is most effective including extensively and partially hydrolysed formulas. To determine which infants benefit, including infants at low or high risk of allergy and infants receiving early, short term or prolonged formula feeding.

SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. The review was updated with searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006) and CINAHL (1982-March 2006) and previous reviews including cross references.

SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of a hydrolysed infant formula to human milk or cow's milk formula. Trials with >80% follow up of participants were eligible for inclusion.

DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Meta-analysis was conducted using a fixed effects model.

MAIN RESULTS: Two trials compared early, short term hydrolysed formula to human milk feeding. No significant difference in infant allergy or childhood cow's milk allergy (CMA) were reported. No eligible trial compared prolonged hydrolysed formula to human milk feeding. Two trials compared early, short term hydrolysed formula to cow's milk formula feeding. No significant benefits were reported. One large quasi-random study reported a reduction in infant CMA of borderline significance in low risk infants (RR 0.62, 95% CI 0.38, 1.00). Ten eligible studies compared prolonged feeding with hydrolysed formula versus cow's milk formula in high risk infants. Meta-analysis found a significant reduction in infant allergy (seven studies, 2514 infants; typical RR 0.79, 95% CI 0.66, 0.94), but not in the incidence of childhood allergy (two studies, 950 infants; typical RR 0.85, 95% CI 0.69, 1.05). There was no significant difference in infant eczema (eight studies, 2558 infants, typical RR 0.84, 95% CI 0.68, 1.04), childhood eczema incidence (two studies, 950 infants, typical RR 0.83, 95% CI 0.63, 1.10), childhood eczema prevalence (one study, 872 infants; RR 0.66, 95% CI 0.43, 1.02), or infant or childhood asthma, rhinitis and food allergy. One study reported a significant reduction in infants with CMA with confirmed atopy (RR 0.36, 95% CI 0.15, 0.89). Subgroup analysis of trials blinded to formula found no significant difference in infant allergy (four studies, 2156 infants; typical RR 0.87, 95% CI 0.69, 1.08) or childhood allergy incidence (one study, 872 infants; RR 0.91, 95% CI 0.73, 1.14). No eligible trial examined the effect of prolonged hydrolysed formula feeding on allergy beyond early childhood. There is evidence that preterm or low birthweight infants fed a hydrolysed preterm formula have significantly reduced weight gain, but not in other growth parameters (head circumference or length). Studies in term infants report no adverse effects on growth. Subgroup analysis of trials of partially hydrolysed versus cow's milk formula found a significant reduction in infant allergy (six studies, 1391 infants; typical RR 0.79, 95% CI 0.65, 0.97) but not childhood allergy, or infant or childhood asthma, eczema or rhinitis. Methodological concerns were the same as for the overall analysis. Analysis of trials of extensively hydrolysed formula versus cow's milk formula found no significant differences in allergy or food intolerance. Infants fed extensively hydrolysed formula compared with partially hydrolysed formula had a significant reduction in food allergy (two studies, 341 infants; typical RR 0.43, 95% CI 0.19, 0.99), but there was no significant difference in all allergy or any other specific allergy incidence. Comparing extensively hydrolysed casein containing formula with cow's milk formula, one study (431 infants) reported a significant reduction in childhood allergy incidence (RR 0.72, 95% CI 0.53, 0.97). Meta-analysis found a significant reduction in infant eczema (three studies, 1237 infants; typical RR 0.71, 95% CI 0.51, 0.97). One study reported a significant reduction in childhood eczema incidence (RR 0.66, 95% CI 0.44, 0.98) and prevalence (RR 0.50, 95% CI 0.27, 0.92).

AUTHORS' CONCLUSIONS: There is no evidence to support feeding with a hydrolysed formula for the prevention of allergy compared to exclusive breast feeding. In high risk infants who are unable to be completely breast fed, there is limited evidence that prolonged feeding with a hydrolysed formula compared to a cow's milk formula reduces infant and childhood allergy and infant CMA. In view of methodological concerns and inconsistency of findings, further large, well designed trials comparing formulas containing partially hydrolysed whey, or extensively hydrolysed casein to cow's milk formulas are needed.

PMID: 17054180

Cochrane Database Syst Rev. 2006 Oct 18;(4):CD003741.

Soy formula for prevention of allergy and food intolerance in infants.

Osborn DA, Sinn J.

Westmead Hospital, Neonatal Unit, Hawkesbury Road, Westmead, New South Wales, Australia.

Update of:

Cochrane Database Syst Rev. 2004;(3):CD003741. 

Abstract

BACKGROUND: Allergies and food reactions in infants and children are common and may be associated with a variety of foods including adapted cow's milk formula. Soy based formulas have been used to treat infants with allergy or food intolerance. However, it is unclear whether they can help prevent allergy and food intolerance in infants without clinical evidence of allergy or food intolerance.

OBJECTIVES: To determine the effect of feeding adapted soy formula compared to human milk, cow's milk formula or a hydrolysed protein formula on preventing allergy or food intolerance in infants without clinical evidence of allergy or food intolerance.

SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. Updated searches were performed of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966-March 2006), EMBASE (1980-March 2006), CINAHL (1982-March 2006) and previous reviews including cross references.

SELECTION CRITERIA: Randomised and quasi-randomised trials that compare the use of an adapted soy formula to human milk, an adapted cow's milk or a hydrolysed protein formula for feeding infants without clinical allergy or food intolerance in the first six months of life. Only trials with > 80% follow up of participants and reported in group of assignment were eligible for inclusion.

DATA COLLECTION AND ANALYSIS: Eligibility of studies for inclusion, methodological quality and data extraction were assessed independently by each review author. Primary outcomes included clinical allergy, specific allergies and food intolerance. Where no heterogeneity of treatment effect was found, the fixed effect model was used for meta-analysis. Where significant or apparent heterogeneity was found, results were reported using the random effects model and potential causes of the heterogeneity were sought.

MAIN RESULTS: Three eligible studies enrolling high risk infants with a history of allergy in a first degree relative were included. No eligible study enrolled infants fed human milk. No study examined the effect of early, short term soy formula feeding. All compared prolonged soy formula to cow's milk formula feeding. One study was of adequate methodology and without unbalanced allergy preventing co-interventions in treatment groups. One study with unclear allocation concealment and 19.5% losses reported a significant reduction in infant allergy, asthma and allergic rhinitis. However, no other study reported any significant benefits from the use of a soy formula. Meta-analysis found no significant difference in childhood allergy incidence (2 studies; typical RR 0.73, 95% CI 0.37, 1.44). No significant difference was reported in one study in infant asthma (RR 1.10, 95% CI 0.86, 1.40), infant eczema (RR 1.20, 95% CI 0.95, 1.52), childhood eczema prevalence (RR 1.10, 95% CI 0.73, 1.68), infant rhinitis (RR 0.94, 95% CI 0.76, 1.16) or childhood rhinitis prevalence (RR 1.20, 95% CI 0.73, 2.00). Meta-analysis found no significant difference in childhood asthma incidence (3 studies, 728 infants; typical RR 0.71, 95% CI 0.26, 1.92), childhood eczema incidence (2 studies, 283 infants; typical RR 1.57, 95% CI 0.90, 2.75) or childhood rhinitis incidence (2 studies, 283 infants; typical RR 0.69, 95% CI 0.06, 8.00). One study reported no significant difference in infant CMPI (RR 1.09, 95% CI 0.45, 2.62), infant CMA (RR 1.09, 95% CI 0.24, 4.86), childhood soy protein allergy incidence (RR 3.26, 95% CI 0.36, 29.17) and urticaria. No study compared soy formula to hydrolysed protein formula.

AUTHORS' CONCLUSIONS: Feeding with a soy formula cannot be recommended for prevention of allergy or food intolerance in infants at high risk of allergy or food intolerance. Further research may be warranted to determine the role of soy formulas for prevention of allergy or food intolerance in infants unable to be breast fed with a strong family history of allergy or cow's milk protein intolerance.

PMID: 17054183

Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006475.

Probiotics in infants for prevention of allergic disease and food hypersensitivity.

Osborn DA, Sinn JK.

Abstract

BACKGROUND: The composition of the intestinal microflora may be different in individuals with atopic eczema from those without this condition, and such differences may precede the development of eczema. Probiotics are live bacteria that colonize the gastrointestinal tract and provide a health benefit to the host. Probiotics added to infant feeds have the potential to prevent sensitisation of infants to dietary allergens.

OBJECTIVES: To determine the effect of probiotics given to infants for the prevention of allergic disease or food hypersensitivity.

SEARCH STRATEGY: This included searches of the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (1966 - February 2007), EMBASE, PREMEDLINE, abstracts of conference proceedings and citations of published articles, and expert informants.

SELECTION CRITERIA: Randomised and quasi-randomised controlled trials that compare the use of a probiotic to no probiotic; or the use a specific probiotic compared to a different probiotic; or a probiotic with added prebiotic to control.

DATA COLLECTION AND ANALYSIS: Assessment of trial quality, data extraction and synthesis of data were performed using standard methods of the Cochrane Neonatal Review Group.

MAIN RESULTS: Twelve studies were eligible for inclusion. Allergic disease and / or food hypersensitivity outcomes were assessed by 6 studies enrolling 2080 infants, but outcomes for only 1549 infants were reported. Studies generally had adequate randomisation, allocation concealment and blinding of treatment. However, the findings of this review should be treated with caution due to excess losses in patient follow-up (17% to 61%). Meta-analysis of five studies reporting the outcomes of 1477 infants found a significant reduction in infant eczema (typical RR 0.82, 95% CI 0.70, 0.95). However, there was significant and substantial heterogeneity between studies. One study reported that the difference in eczema between groups persisted to 4 years age. When the analysis was restricted to studies reporting atopic eczema (confirmed by skin prick test or specific IgE), the findings were no longer significant (typical RR 0.80, 95% CI 0.62, 1.02). All studies reporting significant benefits used probiotic supplements containing L. rhamnosus and enrolled infants at high risk of allergy. No other benefits were reported for any other allergic disease or food hypersensitivity outcome.

AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend the addition of probiotics to infant feeds for prevention of allergic disease or food hypersensitivity. Although there was a reduction in clinical eczema in infants, this effect was not consistent between studies and caution is advised in view of methodological concerns regarding included studies. Further studies are required to determine whether the findings are reproducible.

PMID: 17943912

J Altern Complement Med. 2010 Jan;16(1):69-79.

The use of homeopathic products in childhood: data generated over 8.5 years from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Thompson EA, Bishop JL, Northstone K.

Bristol Homeopathic Hospital, Bristol, United Kingdom. Elizabeth.Thompson@UHBristol.nhs.uk

Abstract

BACKGROUND: Very little is known about the use of homeopathic products (HP) in children. The Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based cohort in the South-West of England, has collected homeopathic data through self-completion questionnaires posted to the mother at regular time points throughout childhood. The aim of this article is to describe the use of these products in a large cohort of children from birth to 8.5 years of age.

METHODS: Questions asked about the use of HP within a preceding time period at seven time points from birth to 8.5 years of age. Additional questions at 18 and 81 months asked about the conditions treated and at 81 months who had prescribed the HP.

RESULTS: Eleven and eight-tenths percent (11.8%) of this cohort used a HP at least once up to 8.5 years of age. Chamomilla for teething and Arnica for soft-tissue bruising were the most commonly used products. The most frequently prescribed products were for common self-limiting infantile conditions such as colic, cuts and bruises, and teething. Parents were most likely at 81 months to prescribe HP for their children (46.3% of all prescription sources) and 10% of products were prescribed by general practitioners. Confusion about what constituted a HP was present in nearly 10% of answers.

CONCLUSIONS: No other study, to our knowledge, has been able to map the use of HP over such a long time period in such a large cohort of children. The amount of HP use reflects a significant minority of the population who use complementary and alternative medicine treatments to manage the health of their family. Health care professionals should be aware of the confusion surrounding HP and have knowledge around some of the more commonly used HP. Parents and carers are using homeopathy wisely with appropriate remedies consistently used for acute problems. Research could focus on greater information delivery to the community and monitoring of potential health and cost benefits, or side-effects of the use of HP for acute and chronic conditions in children.

PMID: 20105063

BMC Fam Pract. 2008 Jan 30;9:8.

Complementary or alternative? The use of homeopathic products and antibiotics amongst pre-school children.

Wye L, Hay AD, Northstone K, Bishop J, Headley J, Thompson E.

Academic Unit of Primary Health Care, Community Based Medicine, University of Bristol, Cotham House, Cotham Hill, Bristol, UK. lesley.wye@bristol.ac.uk

Abstract

BACKGROUND: Any intervention to reduce the inappropriate use of antibiotics for infections in children has the potential to reduce the selective pressure on antimicrobial resistance and minimise the medicalisation of self-limiting illness. Little is known about whether homeopathic products might be used by some families as an alternative to antibiotics or the characteristics of such families. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) observational dataset to explore the hypothesis that the use of homeopathic products is associated with reduced antibiotic use in pre-school children and to identify characteristics of the families of pre-school children given homeopathic products.

METHODS: Questionnaires data were completed by the parents of 9723 children while aged between 3-4.5 years in Bristol UK. Univariable and multivariable analyses were used to explore the relationships between antibiotic and homeopathic product use.

RESULTS: Six percent of children had received one or more homeopathic products and 62% one or more antibiotics between the ages of 3 and 4.5 years. After adjustment for factors associated with antibiotic use, there was no association between homeopathic product and antibiotic use (adjusted OR = 1.02, 95% CI 0.84, 1.24). Factors independently associated with child homeopathic product use were: higher maternal education, maternal use of homeopathic products, maternal lack of confidence in doctors, mothers reporting that they were less likely to see doctor when the child was ill, children being given vitamins, watching less television and suffering from wheeze and food allergies.

CONCLUSION: In this observational study, the use of homeopathic products was not associated with decreased antibiotic consumption, suggesting the use of homeopathic product complements rather than competes with the use of antibiotics in pre-school children. The characteristics of mothers giving homeopathic products to their children are similar to those associated with adult self-administration.

PMID: 18234084

Pediatr Int. 2007 Jun;49(3):328-34.

Effects of Spascupreel versus hyoscine butylbromide for gastrointestinal cramps in children.

Müller-Krampe B, Oberbaum M, Klein P, Weiser M.

Abstract

BACKGROUND: Gastrointestinal spasms and cramps are common in children as well as in adults. Alternative medical practices such as chiropractic and homeopathy are becoming increasingly popular in Europe and the USA. The effectiveness and tolerability of the homeopathic preparation Spascupreel was compared with that of hyoscine butylbromide treatment in children <12 years of age.

METHODS: An observational cohort study in 204 children <12 years was conducted over a 1 week treatment period. The efficacy of the respective therapies were evaluated on the effect on severity of spasms and clinical symptoms (pain/cramps, sleep disturbances, distress, eating or drinking difficulties and frequent crying). Compliance was evaluated on a four-point scale from 'very good' to 'low'. Evaluation was done by the practitioner based on information given by the patient or minder.

RESULTS: The analysis showed comparative improvements with the homeopathic preparation and hyoscine butylbromide therapy on severity of spasms, pain/cramps, sleep disturbances, eating or drinking difficulties, and frequent crying, all as evaluated by the practitioner. Both treatments were very well tolerated.

CONCLUSIONS: For patients opting for a homeopathic therapy, Spascupreel seems to be an effective and well tolerated alternative to conventional therapies in children suffering from gastrointestinal spasms.

PMID: 17532830

http://en.wikipedia.org/wiki/Butylscopolamine 

Br J Clin Pharmacol. 2005 Jun;59(6):743-9.

Paediatric homoeopathy in general practice: where, when and why?

Ekins-Daukes S, Helms PJ, Taylor MW, Simpson CR, McLay JS.

Department of Medicine and Therapeutics, The University of Aberdeen, Polwarth Buildings, Foresterhill, Aberdeen, AB25 2ZD.

Abstract

AIMS: To investigate the extent of homoeopathic prescribing in primary care for childhood diseases and assess GP attitudes towards the use of homoeopathy in children.

METHODS: Homoeopathic prescribing in primary care was assessed in 167 865 children aged 0-16 years for the year 1999-2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Medical attitudes towards homoeopathic prescribing to children were also assessed via a questionnaire survey.

RESULTS: During the year 1999-2000 22% (36) of general practices prescribed homoeopathic medicines to 190 (1.1/1000 registered) children. The majority of such prescriptions were issued to children under 1 year of age (8.0/1000 registered children). The most frequently prescribed medicines were for common self-limiting infantile conditions such as colic, cuts and bruises, and teething. A total of 259 completed questionnaires were returned by GPs, giving a response rate of 75%. GPs who frequently prescribed homoeopathic medicines to children (more than 1 per month) were more likely to claim an interest in homoeopathy, have had a formal training and keep up to date in the discipline, and refer on to a homoeopath (P < 0.001 for all variables) than those GPs who prescribed less than once a month or never. The majority of GPs who prescribed homoeopathic medicines did so when conventional treatments had apparently failed (76%), while 94% also perceived homoeopathy to be safe. Frequent prescribers reported a more positive attitude towards homoeopathic medicines than those who prescribed less frequently. Non-prescribers reported a lack of proven efficacy and lack of training as the main reasons for not prescribing homoeopathic medicines (55% and 79%, respectively). However non-prescribers from within homoeopathic prescribing practices reported a more favourable attitude in general towards homoeopathy and less resistance towards prescribing in the future than non-prescribers from practices where none of the partners practiced homoeopathy.

CONCLUSIONS: In primary care paediatric prescribing of homoeopathic medicines most commonly occurs for self-limiting conditions in infants less than 1 year of age. Although the current level of homoeopathic prescribing is low, the widespread use in the community suggests that at least some knowledge of the main indications for homoeopathy and the preparations used would be of benefit to registered medical practitioners.

PMID: 15948942

Summary: Colonoscopy saved my life, but I was bleeding before I had one. The U.S. continues to use it as a screening test, without large studies. The Canadian response is that the harm possible from colonoscopy equals the possible colon cancer prevention if done widely on non-symptomatic patients.

Screening for Colorectal Cancer: An Updated Systematic Review [Internet].

Editors

Whitlock EP, Lin J, Liles E, Beil T, Fu R, O'Connor E, Thompson RN, Cardenas T. 

Rockville (MD): Agency for Healthcare Research and Quality (US); 2008 Oct. Report No.: 08-05-05124-EF-1.

U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews.

Excerpt

PURPOSE: 

We conducted a systematic review of five key questions to assist the U.S. Preventive Services Task Force (USPSTF) in updating its 2002 recommendation for colorectal cancer (CRC) screening in average-risk adults aged 50 years or older using home fecal occult blood testing (FOBT), flexible sigmoidoscopy (FS), FS and FOBT, colonoscopy, or double-contrast barium enema (DCBE). Key questions for this updated review primarily focused on evidence gaps from the previous review: 1) the accuracy (one-time test performance characteristics) and potential harms of newer CRC screening tests—fecal immunochemical tests (FIT), high-sensitivity FOBT, fecal DNA testing, and CT colonography (CTC)—as possible substitutes for currently recommended CRC screening modalities; 2) updating of evidence on the impact of CRC screening on mortality and to estimate the accuracy and harms of colonoscopy and FS in the community setting. A concurrent decision analysis done by others addressed screening program performance, and compared the life-years gained using different CRC screening tests, test intervals, and stopping ages.

STUDY SELECTION: 

We conducted five literature searches of MEDLINE and the Cochrane Library through January 2008. We identified 3948 abstracts from these searches and 488 articles identified from literature searches and outside sources, which we reviewed against specified inclusion-exclusion criteria. Articles were also excluded for quality reasons. Two reviewers' assents were required to exclude a study.

DATA EXTRACTION: 

One investigator abstracted key elements of all included studies into standardized evidence tables. A second reviewer verified these data. Two investigators critically appraised and quality-rated all studies. Disagreements were resolved by consensus.

DATA SYNTHESIS: 

We reported quantitative synthesis for results of each key question, where possible, and qualitative synthesis otherwise. Impact of Screening on CRC Mortality. We found no new studies of CRC screening that report mortality outcomes; longer-term follow-up of four biennial FOBT screening trials indicates CRC mortality was reduced 13 to 21 percent after 8 to 13 years of screening in two trials, although another two trials did not show mortality benefit until after 15 to18 years of screening. The Cochrane Collaboration's pooled estimate of CRC mortality reduction in all four FOBT trials at last follow-up was 15 percent, using either random or fixed-effect models (RR 0.85, CI: 0.78,0.92). FITs, HemeSensa, fecal DNA. The largest body of evidence to evaluate screening test performance of newer fecal tests in average-risk screening populations is for fecal immunochemical tests (FITs), which cannot be analyzed as a class, but as individual assay types. Specifically, four individual FITs (Magstream/HemeSelect; FlexSure OBT/Hemoccult ICT; OC-Hemodia; Monohaem) have higher sensitivity for CRC (61 to 91 percent) than estimates for nonrehydrated Hemoccult II (25 to 38 percent) from another recent systematic review, with somewhat reduced specificity (91 to 97 percent). Sensitivity for advanced neoplasia or large adenomas is less commonly reported, but ranges between 20 and 67 percent in FITs, which is comparable or superior to the sensitivity for nonrehydrated Hemoccult II. Better detection appears to occur with 2 to 3 days of sample collection. For FITs, however, there is a mismatch between tests with clinical accuracy data and those with FDA approval and current US market availability. Of the four FITs discussed here, FlexSure OBT/Hemoccult ICT is the only FIT that is both FDA approved and on the US market at the time of this article. Fewer acceptable-quality studies evaluate Hemoccult Sensa, and although it appears to improve sensitivity for CRC (64 to 80 percent), it may also lower specificity (87 to 90 percent). Clinical accuracy data on fecal DNA tests is still too limited to support population screening, and there is a mismatch between available clinical studies and commercially available tests. Where test accuracy results do not indicate superior test sensitivity with comparable specificity, determining the trade-offs between sensitivity and specificity of newer tests for fecal CRC screening in a program of CRC screening requires modeling. CT Colonography. Published reports on CT colonography (CTC) screening suggest at least comparable sensitivity to colonoscopy for CRC and large adenomas (10 mm or larger). For smaller polyps (6 mm or larger), published data are inconsistent, with some studies suggesting reduced sensitivity or sensitivity, perhaps contingent upon the CT technology used and the individual reader. Published specificity estimates for CTC are consistently high (≥ 96 percent) for large polyps, but appear lower and more variable (80 to 94 percent) for smaller polyps (6 mm or larger). Test performance estimates will be more precise (more than doubling the number of average-risk patients studied with CTC screening) when currently unpublished data from the ACRIN study are made available. Based on currently published studies, as few as 1 in 8 to 1 in 13 of those screened with CTC would be referred for colonoscopy (if the referral threshold is CTC-detected lesions of 10 mm or greater), or, as many as 1 in 3 to 1 in 5 would be referred for colonoscopy (if the referral threshold is CTC-detected lesions of 6 mm or greater). Few procedure-related harms associated with CTC have been reported, although low-dose ionizing radiation is a potential harm. Additionally, extracolonic findings are relatively common (27 to 69 percent have any findings; 4 to 10 percent have findings of high clinical significance that require treatment or diagnostic evaluation; 5 to 27 percent have findings that would likely require investigation and/or further treatment); the net impact of all of these, in terms of added benefit (or harms), is uncertain. Accuracy and Harms of FS and Colonoscopy in Community Settings. In community settings, FS (with or without biopsy to determine colonoscopy referral) has an estimated sensitivity of 58 to 75 percent for CRC in the entire colon (based on small numbers) and an estimated sensitivity of 72 to 86 percent for advanced neoplasia. Variations in these estimates are likely due to differences in examiner skill and the patient's risks for proximal lesions in the unexamined colon. The performance of FS screening will become more clear after results of current randomized controlled trials (RCT) are reported. While colonoscopy remains the most accurate screening test for CRC at a single application, recent CTC studies have confirmed that colonoscopy misses polyps and may also miss CRC. Colonoscopy also presents a higher risk for harms than other tests. Serious harms from community endoscopies are about ten times more common with colonoscopy (3.1 per 1000 procedures) than with FS (3.4 per 10,000 procedures). The estimates for harms from FS, however, have much wider confidence intervals.

LIMITATIONS: 

We reviewed the accuracy or harms of a CRC screening test in a single application for each question in this systematic review. The USPSTF commissioned a simultaneous decision analysis comparing different CRC screening programs that addressed repeated screening. Other topics beyond the scope of this review include barium enema for CRC screening, the adherence or acceptability of various CRC screening methods, methods to improve CRC screening rates, and cost-effectiveness.

CONCLUSIONS: 

Based on currently available evidence, refinements in current CRC screening recommendations to add some fecal tests appear warranted. Given potential harms and variation in test accuracy, emphasis on quality standards for implementation of recommended operator-dependent CRC screening tests also appears prudent. Re-evaluation may be appropriate once ongoing RCTs, particularly evaluating CTC, but also evaluating FS and fecal DNA, report their results. Screening for CRC has a rapidly evolving science base, such that guidance may be expected to change as additional research becomes available.

PMID: 20722162 [PubMed]

Ont Health Technol Assess Ser. 2009;9(10):1-40. Epub 2009 Sep 1.

Fecal occult blood test for colorectal cancer screening: an evidence-based analysis.

Health Quality Ontario.

Abstract

The colorectal cancer (CRC) screening project was undertaken by the Medical Advisory Secretariat (MAS) in collaboration with the Cancer Care Ontario (CCO).In November 2007, the Ontario Health Technology Advisory Committee (OHTAC) MAS to conduct an evidence-based analysis of the available data with respect to colorectal cancer diagnosis and prevention. The general purpose of the project was to investigate the effectiveness, cost effectiveness, and safety of the various methods and techniques used for colorectal cancer screening in average risk people, 50 years of age and older.The options currently offered for colorectal cancer screening were reviewed and five technologies were selected for review:Computed tomographic (CT) colonographyMagnetic resonance (MR) colonographyWireless capsule endoscopy (PillCam Colon)Fecal occult blood test (FOBT)Flexible sigmoidoscopyIn this review, colonoscopy was considered as the "gold standard" technique by which the effectiveness of all other modalities could be evaluated. An economic analysis was also conducted to determine cost-effectiveness of different screening modalities.Evidence-based analyses have been prepared for each of these technologies, as well as summary document that includes an economic analysis, all of which are presented at the MAS Web site: http://www.health.gov.on.ca/english/providers/program/mas/tech/techmn.html

OBJECTIVE: 

The objective of this evidence review is to examine the effectiveness and cost-effectiveness of fecal occult blood testing (FOBT), including guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT), for use in colorectal cancer (CRC) screening in asymptomatic, average-risk adults. Specifically: Is the use of gFOBT or iFOBT associated with a reduction in CRC and overall mortality?What are the sensitivity and specificity of gFOBT and iFOBT for the detection of 1) CRC and 2) large polyps (≥ 1 cm)? CLINICAL NEED: CRC is the most common cause of non-tobacco related cancer death in Canada. It has been estimated that in 2007, 7,800 people were diagnosed with CRC in Ontario and 3,250 died from the disease, making the province's incidence and mortality rate of CRC amongst the highest in the world. DESCRIPTION OF TECHNOLOGY/THERAPY: THERE ARE TWO GENERAL TYPES OF FOBT THAT ARE CATEGORIZED ACCORDING TO THE ANALYTE DETECTED: guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT). Blood in the stool is a nonspecific finding but may originate from CRC or larger (>1 cm) polyps (small adenomatous polyps do not tend to bleed). Bleeding from cancers and larger polyps may be intermittent and not always detectable in a single sample. The FOBT thus requires regular testing that consists of collecting specimens from consecutive bowel movements. A positive gFOBT or iFOBT involves a diagnostic workup with colonoscopy to examine the entire colon in order to rule out the presence of cancer or advanced neoplasia. METHODS OF EVIDENCE-BASED ANALYSIS: A literature search was conducted from January 2003 to June 2008 that included OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), The Cochrane Library, and the International Agency for Health Technology Assessment/Centre for Review and Dissemination.

INCLUSION CRITERIA: 

Patients at average risk for CRCAll patients must be at least 50 years of ageBiennial FOBT as a screening modality and use of colonoscopy as the reference standardSystematic reviews and randomized controlled trials (RCTs)

OUTCOMES: 

CRC mortality, overall mortality, sensitivity, specificity, adverse effects

EXCLUSION CRITERIA:

Studies involving fewer than 100 patientsStudies that do not report sufficient data for analysis COMPARISONS OF INTEREST: Evidence exists for these comparisons of interest: gFOBT compared with the reference "gold standard" colonoscopy (or double-contrast barium enema where colonoscopy is incomplete or contraindicated)iFOBT compared with the reference gold standard colonoscopy (or DCBE where colonoscopy is incomplete or contraindicated)gFOBT compared with iFOBTThe quality of the diagnostic studies was examined according to the 'GRADE Working Group criteria' for grading quality of evidence and strength of recommendations for diagnostic tests and strategies.

SUMMARY OF FINDINGS: 

SINGLE-TEST STUDIES: There is limited direct/indirect evidence that iFOBT has sensitivity/specificity superior to that of unrehydrated gFOBT for CRC detection: sensitivity for gFOBT:13% and 25%pooled iFOBT sensitivity:81%There is evidence that iFOBT and gFOBT have lower sensitivities for adenoma detection than for CRC detection: sensitivity for rehydrated gFOBT22%pooled iFOBT sensitivity28% REPEATED-TEST STUDIES: No trials have examined CRC mortality outcomes after repeated testing of iFOBT. Two RCTs from the United Kingdom and Denmark showed significant reduction in CRC mortality using unrehydrated gFOBT biennially Relative risk reductions of 13% (UK trial) and 16% (Danish trial); absolute difference of 0.1% (UK trial) and 0.2% (Danish trial).No significant reduction in overall mortalityInterval cancers (CRC that develop in the intervals between routine screening) UNITED KINGDOM TRIAL: 236 CRCs detected by positive test, 236 interval CRCs after negative testDANISH TRIAL: 120 CRCs detected by positive test, 146 interval CRCs after negative testUnrehydrated gFOBT has low sensitivity for CRC detection (45% in the UK trial and 54% in the Danish trial). true positive rate50% (United Kingdom and Danish RCTs)false positive rate5%-10%true negative rate90%-95% (from observational studies as RCTs did not report specificity)false negative rate50%ES Table 1:Guaiac FOBT - GRADE Quality of Evidence for InterventionsOutcomeDesignQualityConsistencyDirectnessOverall QualityCRCMortalityRCTDanishN = 137,485United KingdomN = 152,850No seriouslimitationsYes (RR reduction in 2 trials13% and 16%; absolutedifference 0.1% and 0.2%respectively).Age rangeDanish and UnitedKingdom study 45-75yearsHighCRC indicates colorectal cancer; FOBT, fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation; RCT, randomized controlled trial.*Unlikely to be an important uncertainty.ES Table 2:GRADE Quality of Evidence for Diagnostic Tests: Implications of Testing Focusing on AccuracyNew Test and Reference TestPutative BenefitDiagnostic AccuracyPatient Outcomes and Expected Impact on ManagementSensitivitySpecificityTrue PositiveTrue NegativeFalse PositiveFalse NegativePresumed Influence on Outcomes Important to PatientsiFOBT and ColonoscopySimple, non-invasiveLessLessBenefit from diagnosis and treatment after confirmatory colonoscopySmall risk of bowel perforation during colonoscopyBenefit of reassuranceAnxiety/worry leading up to confirmatory colonoscopySmall risk of bowel perforation during confirmatory colonoscopyDetriment from delayed diagnosisDirectness of Evidence (Test Results) for Outcomes Important to PatientsSome uncertainty (until after confirmatory colonoscopy)No UncertaintyUncertaintyUncertaintyFOBT indicates fecal occult blood test; GRADE, Grading of Recommendations Assessment, Development and Evaluation.Es Table 3:Immunochemical FOBT - GRADE Quality of Evidence for Diagnostic StudiesNo. ofStudiesDesignLimitationsIndirectnessInconsistencyImprecise dataQuality6Diagnostic cohort (single test)(reference standard for positive and negative iFOBT results was colonoscopy)No serious limitationsTP Some uncertaintyTN No uncertaintyFP UncertaintyFN UncertaintyTP rate = 69%TN rate = 94%FP rate = 6%FN rate = 30%(from direct comparison study)Diagnostic cohort iFOBT sensitivities: 50% to 90%High I(2)in pooled sensitivity and specificityWide range in confidence intervals in direct comparison studyLow*FN indicates false negative; FOBT, fecal occult blood test; FP, false positive; Development and Evaluation; TN, true negative; TP, true positive.*Uncertainty until after confirmatory colonoscopy†Stress/worry for patient until confirmatory colonoscopy‡Detrimental effects due to delayed diagnosis.§For these 3 reasons, downgrade quality from High to Moderate.║For these 3 reasons, downgrade quality from Moderate to Low. CONSIDERATIONS FOR THE ONTARIO HEALTH SYSTEM: Executive Summary Table 4 shows the potential system pressures and benefit/risk analysis for the use of FOBT and colonoscopy to screen for CRC in average-risk adults, ages 50 and over in Ontario. Es Table 4:Summary of Potential System Pressures for FOBT ScreeningCriterionColonoscopyFOBTPrimarily prevent or detect cancer?Prevent and detectDetectFrequency of screeningEvery 10 yearsMust repeat at regular intervalsEvery 2 yearsMust repeat at regular intervalsLevel of evidenceObservational studiesRCTsBenefitsUsed as gold standard in studiesINTERVENTION GRADE QUALITY: High (gFOBT)DIAGNOSTIC GRADE QUALITY: Low (iFOBT)No RCTs examining the effectiveness of repeated iFOBT on CRC mortality reduction were identifiedLimited direct/indirect evidence that iFOBT has superior sensitivity/specificity to unrehydrated gFOBT for detection of CRCRisks0.1% risk of serious bleeding and perforation requiring surgery0.3% risk of serious complications (stroke/bleeding requiring hospitalization/ myocardial infarction)High interval cancer rateThe small benefit in CRC mortality reduction (absolute difference 0.1% to 0.2%) also coincides with a 0.3% risk of serious complications.Preparation requirementsNo food 1 day prior to examOffice/hospital visitComplete bowel preparationSedationEliminate citrus fruit and juices and vitamin C from diet for 3 days prior to/during stool collection.Person applies 2 samples per bowel movement (each occurring on 3 different days) onto test areas of FOBT cards.Resources required for screening asymptomatic, average-risk adults ≥ 50 yearsIncreased demand for colonoscopies and colonoscopists or nurses who perform colonoscopies. (ABSTRACT TRUNCATED)

PMID: 23074514

Summary: Despite concussions being treated as acute or self-limited, many continue to have effects. An ongoing problem is the acceptance by both patients and caregivers that the new level of functioning is "normal." 

NeuroRehabilitation. 2011 Jan 1;29(4):317-29.

Etiology of the post-concussion syndrome: Physiogenesis and psychogenesis revisited.

Silverberg ND, Iverson GL.

G.F. Strong Rehab Centre, Vancouver, Canada Division of Physical Medicine and Rehabilitation, Department of Medicine, University of British Columbia, Vancouver, Canada.

Abstract

In his seminal article, Physiogenesis and Psychogenesis in the 'Post-Concussional Syndrome,' Lishman (1988) proposed that neurobiological factors account for the development of the post-concussion syndrome and psychological factors become primarily responsible for maintaining it in the chronic phase. Over the 20 years that followed, researchers have advanced our understanding of the etiology of the post-concussion syndrome. Our review of this evidence suggests that neurobiological and psychological factors play a causal role in post-concussion symptoms from the outset, and thus, Lishman's causal model should be updated. If we can clinically identify individuals on a trajectory of poor recovery in the acute post-injury stage, then we can direct secondary prevention towards modifiable risk factors.

PMID: 22207058

Semin Clin Neuropsychiatry. 1997 Jul;2(3):177-187.

Minor Traumatic Brain Injury: A Review of Physiogenesis and Psychogenesis.

Alexander MP.

Memory Disorders Research Center, Boston, MA, USA

Abstract

Mild Traumatic Brain Injury (TBI) has a well defined neuropathology. The natural history of recovery is well understood. The appropriate somatic and psychological treatments are known. Nevertheless, a subset of patients do not recover and may even worsen with time-the persistent post concussive syndrome (PPCS). They are frequently involved in litigation. The risk factors for PPCS are known, and management strategies are available. There is a great risk of inappropriately attributing PPCS to direct neurological injury that cannot be supported by any objective measure. The symptoms and the cognitive deficits in these patients, even when defined by ostensibly objective testing, have no specificity. Accurately distinguishing among the many possible diagnoses in these patients is critical to avoid iatrogenic disability and incorrect treatment.

PMID: 10320459

Pediatrics. 2006 Apr;117(4):e663-74. Epub 2006 Mar 13.

Health care utilization and needs after pediatric traumatic brain injury.

Slomine BS, McCarthy ML, Ding R, MacKenzie EJ, Jaffe KM, Aitken ME, Durbin DR, Christensen JR, Dorsch AM, Paidas CN; CHAT Study Group.

Department of Neuropsychology, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. slomine@kennedykrieger.org

Abstract

OBJECTIVE: 

Children with moderate to severe traumatic brain injury (TBI) show early neurobehavioral deficits that can persist several years after injury. Despite the negative impact that TBI can have on a child's physical, cognitive, and psychosocial well-being, only 1 study to date has documented the receipt of health care services after acute care and the needs of children after TBI. The purpose of this study was to document the health care use and needs of children after a TBI and to identify factors that are associated with unmet or unrecognized health care needs during the first year after injury.

METHODS: 

The health care use and needs of children who sustained a TBI were obtained via telephone interview with a primary caregiver at 2 and 12 months after injury. Of the 330 who enrolled in the study, 302 (92%) completed the 3-month and 288 (87%) completed the 12-month follow-up interviews. The health care needs of each child were categorized as no need, met need, unmet need, or unrecognized need on the basis of the child's use of post-acute services, the caregiver's report of unmet need, and the caregiver's report of the child's functioning as measured by the Pediatric Quality of Life Inventory (PedsQL). Regardless of the use of services or level of function, children of caregivers who reported an unmet need for a health care service were defined as having unmet need. Children who were categorized as having no needs were defined as those who did not receive services; whose caregiver did not report unmet need for a service; and the whose physical, socioemotional, and cognitive functioning was reported to be normal by the caregiver. Children with met needs were those who used services in a particular domain and whose caregivers did not report need for additional services. Finally, children with unrecognized needs were those whose caregiver reported cognitive, physical, or socioemotional dysfunction; who were not receiving services to address the dysfunction; and whose caregiver did not report unmet need for services. Polytomous logistic regression was used to model unmet and unrecognized need at 3 and 12 months after injury as a function of child, family, and injury characteristics.

RESULTS: 

At 3 months after injury, 62% of the study sample reported receiving at least 1 outpatient health care service. Most frequently, children visited a doctor (56%) or a physical therapist (27%); however, 37% of caregivers reported that their child did not see a physician at all during the first year after injury. At 3 and 12 months after injury, 26% and 31% of children, respectively, had unmet/unrecognized health care needs. The most frequent type of unmet or unrecognized need was for cognitive services. The top 3 reasons for unmet need at 3 and 12 months were (1) not recommended by doctor (34% and 31%); (2) not recommended/provided by school (16% and 17%); and (3) cost too much (16% and 16%). Factors that were associated with unmet or unrecognized need changed over time. At 3 months after injury, the caregivers of children with a preexisting psychosocial condition were 3 times more likely to report unmet need compared with children who did not have one. Also, female caregivers were significantly more likely to report unmet need compared with male caregivers. Finally, the caregivers of children with Medicaid were almost 2 times more likely to report unmet need compared with children who were covered by commercial insurance. The only factor that was associated with unrecognized need at 3 months after injury was abnormal family functioning. At 12 months after injury, although TBI severity was not significant, children who sustained a major associated injury were 2 times more likely to report unmet need compared with children who did not. Consistent with the 3-month results, the caregivers of children with Medicaid were significantly more likely to report unmet needs at 1 year after injury. In addition to poor family functioning's being associated with unrecognized need, nonwhite children were significantly more likely to have unrecognized needs at 1 year compared with white children.

CONCLUSIONS: 

A substantial proportion of children with TBI had unmet or unrecognized health care needs during the first year after injury. It is recommended that pediatricians be involved in the post-acute care follow-up of children with TBI to ensure that the injured child's needs are being addressed in a timely and appropriate manner. One of the recommendations that trauma center providers should make on hospital discharge is that the parent/primary caregiver schedule a visit with the child's pediatrician regardless of the post-acute services that the child may be receiving. Because unmet and unrecognized need was highest for cognitive services, it is important to screen for cognitive dysfunction in the primary care setting. Finally, because the health care needs of children with TBI change over time, it is important for pediatricians to monitor their recovery to ensure that children with TBI receive the services that they need to restore their health after injury.

PMID: 16533894

Neurocrit Care. 2010 Jun;12(3):324-36.

Metabolic crisis after traumatic brain injury is associated with a novel microdialysis proteome.

Lakshmanan R, Loo JA, Drake T, Leblanc J, Ytterberg AJ, McArthur DL, Etchepare M, Vespa PM.

UCLA Department of Chemistry and Biochemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Abstract

BACKGROUND: 

To examine if the metabolic distress after traumatic brain injury (TBI) is associated with a unique proteome.

METHODS: 

Patients with severe TBI prospectively underwent cerebral microdialysis for the initial 96 h after injury. Hourly sampling of metabolism was performed and patients were categorized as having normal or abnormal metabolism as evidenced by the lactate/pyruvate ratio (LPR) threshold of 40. The microdialysate was frozen for proteomic batch processing retrospectively. We employed two different routes of proteomic techniques utilizing mass spectrometry (MS) and categorized as diagnostic and biomarker identification approaches. The diagnostic approach was aimed at finding a signature of MS peaks which can differentiate these two groups. We did this by enriching for intact peptides followed by MALDI-MS analysis. For the biomarker identification approach, we applied classical bottom-up (trypsin digestion followed by LC-MS/MS) proteomic methodologies.

RESULTS: 

Five patients were studied, 3 of whom had abnormal metabolism and 2 who had normal metabolism. By comparison, the abnormal group had higher LPR (1609 +/- 3691 vs. 15.5 +/- 6.8, P < 0.001), higher glutamate (157 +/- 84 vs. 1.8 +/- 1.4 microM, P < 0.001), and lower glucose (0.27 +/- 0.35 vs. 1.8 +/- 1.1 mmol/l, P < 0.001). The abnormal group demonstrated 13 unique proteins as compared with the normal group in the microdialysate. These proteins consisted of cytoarchitectural proteins, as well as blood breakdown proteins, and a few mitochondrial proteins. A unique as yet to be characterized peptide was found at m/z (mass/charge) 4733.5, which may represent a novel biomarker of metabolic distress.

CONCLUSION: 

Metabolic distress after TBI is associated with a differential proteome that indicates cellular destruction during the acute phase of illness. This suggests that metabolic distress has immediate cellular consequences after TBI.

PMID: 20225002

Mol Cell Biochem. 2010 Feb;335(1-2):127-36. Epub 2009 Sep 17.

Regulated expression of pancreatic triglyceride lipase after rat traumatic brain injury.

Jia J, Yan M, Lu Z, Sun M, He J, Xia C.

Source

Cytoneurobiology Unit & Laboratory of Aging and Nervous Diseases, Medical College of Soochow University, Suzhou Industrial Park, Suzhou, Jiangsu 215123, People's Republic of China.

Abstract

Pancreatic triglyceride lipase (PTL), an enzyme of digestive system, plays very important roles in the digestion and absorption of lipids. However, its distribution and function in the central nervous system (CNS) remains unclear. In the present study, we mainly investigated the expression and cellular localization of PTL during traumatic brain injury (TBI). Western blot and RT-PCR analysis revealed that PTL was present in normal rat brain cortex. It gradually increased, reached a peak at the 3rd day after TBI, and then decreased. Double immunofluorescence staining showed that PTL was co-expressed with neuron, but had a few colocalizations in astrocytes. When TBI occurred in the rat cortex, the expression of PTL gradually increased, reached the peak at the 3rd day after TBI, and then decreased. Importantly, more PTL was colocalized with astrocytes, which is positive for proliferating cell nuclear antigen (PCNA). In addition, Western blot detection showed that the 3rd day post injury was not only the proliferation peak indicated by the elevated expression of PCNA, glial fibrillary acidic protein (GFAP) and cyclin D1, but also the apoptotic peak implied by the alteration of caspase-3 and bcl-2. These data suggested that PTL may be involved in the pathophysiology of TBI and PTL may be complicated after injury, more PTL was colocalized with astrocytes. Importantly, injury-induced expression of PTL was colabelled by proliferating cell nuclear antigen (proliferating cells marker), and the western blot for GFAP, PCNA and cyclin D1, showed that 3 days post injury was the proliferation peak, in coincidence to it, the protein level change of caspase-3 and bcl-2 revealed that the stage was peak of apoptotic too. These data suggested that PTL may be involved in the pathophysiology of TBI and that PTL may be implicated in the proliferation of astrocytes and the recovery of neurological outcomes. But the inherent mechanisms remained unknown. Further studies are needed to confirm the exact role of PTL after brain injury.

PMID: 19760487

http://www.jbc.org/content/278/44/42899.full

In addition to CEL and PLA2, the pancreas also secretes pancreatic triglyceride lipase (PTL) in response to a lipid meal (14). This protein is a member of the lipase gene family and has been shown in association with colipase to be the primary enzyme in the digestive tract capable of hydrolyzing triglycerides in emulsified lipid particles

Gastroenterology. 1998 Jan;114(1):123-9.

Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release.

Hildebrand P, Petrig C, Burckhardt B, Ketterer S, Lengsfeld H, Fleury A, Hadváry P, Beglinger C.

Division of gastroenterology, University Hospital, Basel, Switzerland.

Abstract

BACKGROUND &#38; AIMS: 

The hypothesis that cholecystokinin release requires adequate dietary fat digestion in the small intestine was investigated in 10 healthy volunteers, and the consequences of reduced fat hydrolysis on pancreaticobiliary secretions were assessed.

METHODS: 

Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses.

RESULTS: 

In the control without tetrahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fatty acid concentration averaged 60% of total fatty acids. Increasing doses of tetrahydrolipstatin induced a dose-dependent inhibition of duodenal lipase activity (P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreased to < 5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% (P < 0.01). Amylase and trypsin outputs were reduced by 77% and 59%, respectively, and bilirubin secretion was virtually abolished (P < 0.01).

CONCLUSIONS: 

These findings show that tetrahydrolipstatin prevents triglyceride hydrolysis and that plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion require adequate triglyceride digestion. These data also support the concept of negative feedback regulation of cholecystokinin secretion.

PMID: 9428226

Am J Physiol Gastrointest Liver Physiol. 2003 May;284(5):G798-807. Epub 2003 Jan 10.

Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans.

Feinle C, O'Donovan D, Doran S, Andrews JM, Wishart J, Chapman I, Horowitz M.

University of Adelaide Department of Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia. christine.feinle@adelaide.edu.au

Abstract

The presence of nutrients in the small intestine slows gastric emptying and suppresses appetite and food intake; these effects are partly mediated by the release of gut hormones, including CCK. We investigated the hypothesis that the modulation of antropyloroduodenal motility, suppression of appetite, and stimulation of CCK and glucagon-like peptide-1 secretion by intraduodenal fat are dependent on triglyceride hydrolysis by lipase. Sixteen healthy, young, lean men were studied twice in double-blind, randomized, crossover fashion. Ratings for appetite-related sensations, antropyloroduodenal motility, and plasma CCK and glucagon-like peptide-1 concentrations were measured during a 120-min duodenal infusion of a triglyceride emulsion (2.8 kcal/min) on one day with, on the other day without, 120 mg tetrahydrolipstatin, a potent lipase inhibitor. Immediately after the duodenal fat infusion, food intake at a buffet lunch was quantified. Lipase inhibition with tetrahydrolipstatin was associated with reductions in tonic and phasic pyloric pressures, increased numbers of isolated antral and duodenal pressure waves, and stimulation of antropyloroduodenal pressure-wave sequences (all P < 0.05). Scores for prospective consumption and food intake at lunch were greater, and nausea scores were slightly less, and the rises in plasma CCK and glucagon-like peptide-1 were abolished (all P < 0.05). In conclusion, lipase inhibition attenuates the effects of duodenal fat on antropyloroduodenal motility, appetite, and CCK and glucagon-like peptide-1 secretion.

PMID: 12684211

Physiol Behav. 2009 Aug 4;98(1-2):198-204. Epub 2009 May 22.

Dose-response effects of PEGylated cholecystokinin on the behavioral satiety sequence.

Verbaeys I, León-Tamariz F, De Buyser K, Buyse J, Decuypere E, Pottel H, Cokelaere M.

Interdisciplinary Research Center, Katholieke Universiteit Leuven, Campus Kortrijk, Etienne Sabbelaan 53, B-8500, Kortrijk, Belgium. isabelle.verbaeys@kuleuven-kortrijk.be

Abstract

Cholecystokinin (CCK) is known to have a short biological half-life. In order to prolong the half-life and create a new investigative tool, we previously PEGylated the peptide, yielding PEG-CCK(9), and demonstrated that it had a dose-dependent prolonged anorectic effect. The aim of this study was to investigate whether PEG-CCK(9) reduces food intake by inducing satiation or by abnormal physiological effects, such as pain, malaise, or nausea. An observational study was performed to examine the effects of different doses of PEG-CCK(9) (1, 2, 4, 8, or 16 microg kg(-1)) on feeding and other behaviors. The behavioral sequence associated with satiety (BSS), i.e. the orderly progression from eating, through grooming and activity, to resting, was analyzed. From the lowest dose tested (1 microg kg(-1)), PEG-CCK(9) caused a dose-dependent reduction in food intake due to a dose-related reduction in both the duration and frequency of eating and a dose-dependent increase in duration of rest. A dose-dependent acceleration in the temporal profile of the BSS was observed, while the normal structure of feeding behaviors was well preserved, except at the dose of 16 microg kg(-1) of PEG-CCK(9), at which a decrease in eating rate and grooming behavior was observed, together with the occurrence of a significant number of abdominal cramps. These findings suggest that the hypophagic response to PEG-CCK(9) is mainly induced by natural mechanisms of satiety, although abnormal physiological effects, such as abdominal cramps, might reinforce the food inhibitory effect, especially at high doses of PEG-CCK(9) (>8 microg kg(-1)).

PMID: 19465039

Christopher Maloney, N.D. naturopathicmaine.com docmaloneynd@gmail.com

The Dementia Diet: How Not To Lose Your Memories

1. When I was 15, I was diagnosed with Alzheimer’s. (Kills 700,000 U.S. a year).

1. Dr. Herman Weinreb. https://www.ncbi.nlm.nih.gov/pubmed/3966885

2. No follow up for 30 years. I want to make dementia horrible, not terrifying.

2. Alzheimer’s disease

1. Amyloid plaques found in 1906. 55 y.o. Patient

2. Still the dominant model today. Alois died of pneumonia at 51.

3. Fulminant disease Dale Bredesen End of Alzeheimer’s Great stories. Poor follow up.

1. Infectious

2. Autoimmune

3. Chronic disease sequelae

4. Polypharmacy

3. Does Alzheimer’s Exist? Artifact finding. Now mild/moderate neurocognitive decline.

1. Plaque correlation

2. Deterioration correlation

3. Tau, Abeta42 https://www.ncbi.nlm.nih.gov/pubmed/14608585

4. Dietary prevention,

1. Heart, Brain, Kitchen Sink, Math. 

2. Major significant marker?

5. Exercise The Caerphilly Effect 30k folks, South Wales 30 year study.

1. Yes. B. But. Not smoking, drinking < three drinks, walking 4m a day, eating 3+ servings of vegetables and fruits, and keeping a normal body weight. Out of 2k 111 did 4. ⅖.

6. Treatment

1. Drugs https://www.ncbi.nlm.nih.gov/pubmed/30282371 France says no.

2. Increased mortality. Why? Focused on plaque prevention.

3. Do we have any treatment? Yes.

7. Use It Or Lose It

1. No exercise affects the brain globally.

2. Five weeks= two years of benefit.

3. Useful at every age.

8. So why does dementia occur?

1. Decades of depression and withdrawal.

2. Imagine breaking a leg and never using it again.

3. The EB White effect.

9. How do we die? 

1. A year-and-a-half on hospice.

2. Imminent death six times Every time in nursing care.

10. How do we live?

1. Fight, fight against the dying of the light., computer games/school.

2. Hogeway https://www.theatlantic.com/health/archive/2014/11/the-dutch-village-where-everyone-has-dementia/382195/

Other books by Dr. Maloney

For videos and full links go to: https://sites.google.com/view/maloneybooks/home 

CANCER

The Colon Cancer Diet (Updated) Paperback Ebook Audio (Also available in multiple languages: Portuguese, Spanish, German, and French) 

For those diagnosed with colon cancer, how to cut in half your risk of recurrence. 

Related: Walking In The Valley of The Shadow Paperback Ebook (pay what you can) 

My journey through cancer, with gruesome details and my thoughts on faith. 

RARE DISEASES

Helping Your NF1 Child: A Parent's Guide To Neurofibromatosis (NF1) 

Paperback Ebook (coming in other formats)

A layperson’s guide to how the genetics affect the mind and some possible treatments.

(Related: Tending Your Internal Garden Paperback Ebook)

Joint Hypermobility Syndrome (Ehlers-Danlos Syndrome) Paperback Ebook Audio

A discussion of chronic pain and a possible cause.

LYME 

Lyme Free Living In An Infected World Paperback Ebook

Twenty herbs, twenty drugs, and why I hate herxing. 

Why Chronic Lyme Doesn't (And Does) Exist Paperback Ebook

A layperson’s guide to the strange world of Lyme medicine.

GENERAL HEALTH 

Tending Your Internal Garden Paperback Ebook

Why your bowel is a unique rainforest with some gardening tips. 

Your Car For Life: Basic Body Maintenance Paperback Ebook (coming in all formats)

Some general tips on keeping your body on the road.

Shielding 101 Paperback Ebook 

A simple guide for sensitive people who want to be social. 

Zika Virus When You're Expecting Paperback Ebook

Why some women shouldn’t worry and others should be very concerned.

Healing Your Back of Chronic Pain Paperback Ebook

My thoughts on chronic back pain, emotions, and why we don’t heal. 

The Eye Diet Paperback Ebook Audio

How can we keep our sight in a world that is experiencing a pandemic of nearsightedness to the point of blindness?

ALTERNATIVE MEDICINE

M.D. or N.D., What Should I Be? Ebook (pay what you can) 

My thoughts on a career in alternative medicine and why most M.D.s aren’t recommending the field. 

I also write fiction, most recently a climate fiction novel called Miner Six. 

I also explore fantasy topics like the future of the planet, the nature of magic, and how to deal with getting shipwrecked with pirates who like blood. Most are kid appropriate, but write me for recommendations. Go to ChrisJLMaloney for these. 

Hormonal checklist just to see if you're familiar with some of many, many options available to alter female hormones. 

Here’s a short list of some of the basics (originally A-Z, but I really don't want to give the impression that this is anything but a starting point.) 

1. Black cohash 2-4 caps

2. GABA 2 caps daily

3. Multivitamin with women’s herbs (Innate Formulas one a day)

4. Meditation 20 minutes daily

5. Diet Brown, whole, green and colorful, no caloric restriction, no fast food

6. Detox one day a week (vegetable stew/salads)

7. Red meat discussion (20% increase in testosterone in two hours)

8. Dairy discussion (cow hormones still need processing by the body)

9. Alcohol discussion (300% increase in estrogen due to processing delay)

10. Teas raspberry, “Yoni,” female teas

11. Cold packs for pain/hot flashes

12. Progesterone creams

13. Combination creams

14. PhytoB (4 pellets twice a day = one half a standard hormonal dose)

15. Licorice/Ashwaghanda mix

16. Soy (SOYI9)four caps or half a cup of soy a day

17. Sleep discussion (90 minute cycles)

18. Cycle discussion (temperature readings/ journaling)

19. Exercise (adrenal/ thyroid = worse/better) helps process hormones

20. Bowel movements per day (LIQU8) if not at least one.

21. Family history how to avoid/get what mom had.

22. Vitex (VITEX), Chaste Tree-one a day.

23. Weight changes (gain or loss) alter hormonal picture

24. Folic acid 5 mg a day (Gynecol Endocrinol. 2010 Sep;26(9):658-62.)

25. Tyrosine 500mg a day (Actas Urol Esp. 2009 Apr;33(4):337-43.)

26. 5 HTP 50-600mg a day (Serotonin involvement)

The first thing I want to say is that I don't believe in homeopathy. The second thing I want to say is that I often use homeopathy with my patients and I have been very pleased with the results. 

How is that possible?

When we say we believe in something, it means we have a belief system about that thing. If I believe something in a religious way, I have a great deal of thought about that thing's place in my universe. With homeopathy, I use it like I would a wrench. I do not have a strong belief system about wrenches, I just use them because they work. Don't ask me about adjustable vs. fixed wrenches, or try to get me into a discussion about the relative merits of different wrench manufacturers. I'm really not interested and I haven't given it much thought. Here's a post about homeopathy, wrenches, and how homeopathy can cure croup.

Do I have a basis for using homeopathy? A scientific one? 

Yes. I have gone over the arguments quite extensively with good doctors who disagree. Before engaging in another conversation, I would recommend reading through my pages long conversation with Dr. Howell. We go over many of the same points you might bring up. 

Do I think homeopathy is a placebo? That's a complicated answer.

I think that the placebo effect doesn't exist. It hasn't for years. What we see instead is the placebo response, a physical change in the body that is measurable, beneficial, and so powerful it is outdoing many conventional drugs. 

So certainly part of any medical intervention is the placebo response. That includes homeopathy. Anyone who doubts that the placebo response can be lifesaving by itself should read through the Krebiozen effect on cancer. 

But I don't think homeopathy is only a placebo response. I've used it too long and under too many conditions where an expected placebo response has not shown up and another homeopathic remedy has been effective. What is that extra bit? Well, it's something that pushes the edge of what we think we know as common sense about chemistry. One hypothesis is a series of silica interactions with the initial substance. But there are many. The point is not that we have an answer, it's that we should be looking for an answer because we desperately need alternatives to our current medical Titanic. 

Half a million studies

30-40% of patients misdiagnosed in office (white coat hypertension). "a recent review reported that 30%–40% of patients who are diagnosed with hypertension on the basis of their office blood pressure measurement alone have normal out-of-office blood pressure"

Pak J Pharm Sci. 2018 Jan;31(1):237-244.

Review: Beyond conventional therapies: Complementary and alternative medicine in the management of hypertension: An evidence-based review.

Wong AP1, Kassab YW2, Mohamed AL2, Abdul Qader AM1.

Author information

Abstract

Hypertension is one of the major causes of morbidity and mortality. Worldwide, Hypertension is estimated to cause 7.5 million deaths, about 12.8% of the total of all deaths. This accounts for 57 million disability adjusted life years (DALYS) or 3.7% of total DALYS. This led WHO to set a target of 25% reduction in prevalence by 2025. To reach that, WHO has adopted non-conventional methods for the management of hypertension? Despite worldwide popularity of such non-conventional therapies, only small volume of evidence exists that supports its effectiveness. This review attempted to make a critical appraisal of the evidence, with the aim to (1) describe the therapeutic modalities frequently used, and (2) review the current level of evidence attributable to each modality. Databases from Cochrane Library, MEDLINE, PUBMED, and EMBASE were searched from 2005-2015. A total of 23 publications have been identified and selected. Out of these, 15 systematic reviews and/or meta-analysis of RCTs, 5 RCTs, 1 non-RCT, and 2 observational studies without control. Among those 23 publications, therapeutic modalities identified are: fish oil, qigong, yoga, coenzyme Q10, melatonin, meditation, vitamin D, vitamin C, monounsaturated fatty acids, dietary amino-acids, chiropractic, osteopathy, folate, inorganic nitrate, beetroot juice, beetroot bread, magnesium, and L-arginine. The followings were found to have weak or no evidence: fish oil, yoga, vitamin D, monounsaturated fatty acid, dietary amino-acids, and osteopathy. Those found to have significant reduction in blood pressure are: magnesium, qigong, melatonin, meditation, vitamin C, chiropractic, folate, inorganic nitrate, beetroot juice and L-arginine. Coenzyme Q10on the other hand, showed contradicting results were some studies found weak or no effect on blood pressure while others showed significant blood pressure reduction effect. By virtue of the research designs and methodologies, the evidence contributed from these studies is at level 1. Results from this review suggest that certain non-conventional therapies may be effective in treating hypertension and improving cardiac function and therefore considered as part of an evidence-based approach.

PMID:

29348109

Am J Hypertens. 2018 Feb 9. doi: 10.1093/ajh/hpy027. [Epub ahead of print]

Comparative efficacy of antihypertensive agents in salt-sensitive hypertensive patients: a network meta-analysis.

Qi H1, Liu Z1, Cao H1, Sun WP1,2, Peng WJ1, Liu B1, Dong SJ3, Xiang YT4, Zhang L1.

Author information

Abstract

BACKGROUND:

Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure in patients with salt-sensitive hypertension (SSH).

METHODS:

We used sources as PubMed, EMBASE, Cochrane Library, CENTRAL, ClinicalTrials.gov, ICTRP, CNKI and WANFANG database from inception to November 2016. Studies that compared the efficacy of two or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure.

RESULTS:

Twenty-five studies were involved in this meta-analysis. A CCB with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo [standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60-40.16], ARBs [SMD, 95% CI: 22.94, 5.26-40.51] and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, the effect size of CCB with metformin and moderate salt intake was [SMD, 95% CI: 17.90, 6.26 -29.33].

CONCLUSIONS:

For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake were optimal in reducing blood pressure, while CCB combined with metformin and moderate salt intake were the most efficacious at reducing blood pressure in SSH patients with coexisting obesity.

KEYWORDS:

Salt-sensitive hypertension; antihypertensive agents; network meta-analysis

PMID:

29438454

DOI:

10.1093/ajh/hpy027

Cochrane Database Syst Rev. 2017 Jan 20;1:CD002003. doi: 10.1002/14651858.CD002003.pub5.

Beta-blockers for hypertension.

Wiysonge CS1,2, Bradley HA3, Volmink J1,2, Mayosi BM4, Opie LH5.

Author information

Abstract

BACKGROUND:

Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a CochraneReview initially published in 2007 and updated in 2012.

OBJECTIVES:

To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults.

DATA COLLECTION AND ANALYSIS:

We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect).

MAIN RESULTS:

Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol).There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons.Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence). However, there was little or no difference in CHD between beta-blockers and diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS inhibitors (low-certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta-blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate-certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low-certainty evidence).

AUTHORS' CONCLUSIONS:

Most outcome RCTs on beta-blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta-blocker most used. Current evidence suggests that initiating treatment of hypertension with beta-blockers leads to modest CVD reductions and little or no effects on mortality. These beta-blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people.

Update of

• Beta-blockers for hypertension. [Cochrane Database Syst Rev. 2012]

PMID:

28107561

PMCID:

PMC5369873

DOI:

10.1002/14651858.CD002003.pub5

Cochrane Database Syst Rev. 2017 Aug 16;8:CD008276. doi: 10.1002/14651858.CD008276.pub2.

Pharmacotherapy for hypertension in adults aged 18 to 59 years.

Musini VM1, Gueyffier F, Puil L, Salzwedel DM, Wright JM.

Author information

Abstract

BACKGROUND:

Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age.

OBJECTIVES:

To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work.

SELECTION CRITERIA:

Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both.

DATA COLLECTION AND ANALYSIS:

The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity.

MAIN RESULTS:

The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average.

AUTHORS' CONCLUSIONS:

Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.

PMID:

28813123

DOI:

10.1002/14651858.CD008276.pub2

[Indexed for MEDLINE]Cochrane Database Syst Rev. 2017 Aug 8;8:CD011575. doi: 10.1002/14651858.CD011575.pub2.

Blood pressure targets for hypertension in older adults.

Garrison SR1, Kolber MR, Korownyk CS, McCracken RK, Heran BS, Allan GM.

Author information

Abstract

BACKGROUND:

Eight out of 10 major antihypertensive trials in older adults attempted to achieve a target systolic blood pressure (BP) less than 160 mmHg. Collectively these trials demonstrated benefit for treatment, as compared to no treatment, for an older adult with BP greater than 160 mmHg. However an even lower BP target of less than 140 mmHg is commonly applied to all age groups. At the present time it is not known whether a lower or higher BP target is associated with better cardiovascular outcomes in older adults.

OBJECTIVES:

To assess the effects of a higher (less than 150 to 160/95 to 105 mmHg) BP target compared to the lower BP target of less than 140/90 mmHg in hypertensive adults 65 years of age or older.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We also contacted authors of relevant papers regarding further published and unpublished work.

SELECTION CRITERIA:

Randomised trials, of at least one year's duration, conducted on hypertensive adults aged 65 years or older, which report the effect on mortality and morbidity of a higher systolic or diastolic BP treatment target (whether ambulatory, home, or office measurements) in the range of systolic BP less than 150 to 160 mmHg or diastolic BP less than 95 to 105 mmHg as compared to a lower BP treatment target of less than 140/90 mmHg or lower.

DATA COLLECTION AND ANALYSIS:

Two authors independently screened and selected trials for inclusion, assessed risk of bias, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI) and for continuous outcomes we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and cardiovascular serious adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved.

MAIN RESULTS:

We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects.

AUTHORS' CONCLUSIONS:

At the present time there is insufficient evidence to know whether a higher BP target (less than 150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

PMID:

28787537

DOI:

10.1002/14651858.CD011575.pub2

Nutr J. 2017 May 5;16(1):26. doi: 10.1186/s12937-017-0247-4.

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

Han H1, Fang X2, Wei X3, Liu Y3, Jin Z1, Chen Q1, Fan Z4, Aaseth J5,6, Hiyoshi A7, He J8, Cao Y9,7.

Author information

Abstract

BACKGROUND:

The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension.

METHODS:

We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects.

RESULTS:

Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02).

CONCLUSIONS:

Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.

KEYWORDS:

Dietary intake; Dose-response relationship; Hypertension; Magnesium; Prospective cohort study; Serum concentration

PMID:

28476161

PMCID:

PMC5420140

DOI:

10.1186/s12937-017-0247-4

PLoS One. 2017 Apr 18;12(4):e0174967. doi: 10.1371/journal.pone.0174967. eCollection 2017.

Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials.

Poorolajal J1,2,3, Zeraati F4, Soltanian AR3,5, Sheikh V6, Hooshmand E7, Maleki A1.

Author information

Abstract

IMPORTANCE:

Increased dietary potassium intake is thought to be associated with low blood pressure (BP). Whether potassiumsupplementation may be used as an antihypertensive agent is a question that should be answered.

OBJECTIVE:

To assess the effect of oral potassium supplementation on blood pressure in patients with primary hypertension.

SEARCH METHODS:

We searched Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials until October 2016. We also screened reference lists of articles and previous reviews. We applied no language restrictions.

SELECTION CRITERIA:

We included randomized placebo-controlled clinical trials addressing the effect of potassium supplementation on primary hypertension for a minimum of 4 weeks.

DATA COLLECTION AND ANALYSIS:

We extracted data on systolic and diastolic BP (SBP and DBP) at the final follow-up. We explored the heterogeneity across studies using Cochran's test and I2 statistic and assessed the probability of publication bias using Begg's and Egger's tests. We reported the mean difference (MD) of SBP and DBP in a random-effects model.

RESULTS:

We found a total of 9059 articles and included 23 trials with 1213 participants. Compared to placebo, potassium supplementation resulted in modest but significant reductions in both SBP (MD -4.25 mmHg; 95% CI: -5.96 to -2.53; I2 = 41%) and DBP (MD -2.53 mmHg; 95% CI: -4.05 to -1.02; I2 = 65%). According to the change-score analysis, based on 8 out of 23 trials, compared to baseline, the mean changes in SBP (MD -8.89 mmHg; 95% CI: -13.67 to -4.11) and DBP (MD -6.42 mmHg; 95% CI: -10.99 to -1.84) was significantly higher in the intervention group than the control group.

CONCLUSIONS:

Our findings indicated that potassium supplementation is a safe medication with no important adverse effects that has a modest but significant impact BP and may be recommended as an adjuvant antihypertensive agent for patients with essential hypertension.

PMID:

28419159

PMCID:

PMC5395164

DOI:

10.1371/journal.pone.0174967

[Indexed for MEDLINE] 

Free PMC Article

Medicine (Baltimore). 2016 Jul;95(30):e4071. doi: 10.1097/MD.0000000000004071.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.

Paz MA1, de-La-Sierra A, Sáez M, Barceló MA, Rodríguez JJ, Castro S, Lagarón C, Garrido JM, Vera P, Coll-de-Tuero G.

Author information

Abstract

BACKGROUND:

The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with best performance of the drugs will improve management of hypertensive patients.

OBJECTIVE:

To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease.

DATA SOURCES:

MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers.

STUDY ELIGIBILITY CRITERIA:

Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data.

STUDY APPRAISAL AND SYNTHESIS METHODS:

Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework.

MAIN OUTCOME(S) AND MEASURE(S):

Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination.

RESULTS:

Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats.

LIMITATIONS:

Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses.

CONCLUSIONS AND IMPLICATIONS:

Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised.

PMID:

27472680

PMCID:

PMC5265817

DOI:

10.1097/MD.0000000000004071

Ugeskr Laeger. 2015 May 11;177(20):949-51.

[Thiazide diuretics in the treatment of hypertensive patients].

[Article in Danish]

Rasmussen K1.

Author information

Abstract

This Cochrane review had the objectives to determine the dose-related decrease in blood pressure due to thiazide diuretics compared with placebo control in the treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2, 6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers as shown in other Cochrane reviews, which have compared these antihypertensive drugs with placebo having used similar inclusion/exclusion criteria.

PMID:

25967243

[Indexed for MEDLINE]

Hypertens Res. 2012 Jan;35(1):77-81. doi: 10.1038/hr.2011.143. Epub 2011 Sep 1.

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel.

Shimizu H1, Nakagami H, Yasumasa N, Mariana OK, Kyutoku M, Koriyama H, Nakagami F, Shimamura M, Rakugi H, Morishita R.

Author information

Abstract

Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine(L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a β-blocker) because β-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.

PMID:

21881574

DOI:

10.1038/hr.2011.143

Ophthalmology. 2018 Feb 9. pii: S0161-6420(17)30944-2. doi: 10.1016/j.ophtha.2018.01.007. [Epub ahead of print]

Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma.

Zheng W1, Dryja TP1, Wei Z2, Song D2, Tian H3, Kahler KH3, Khawaja AP4.

Author information

Abstract

PURPOSE:

To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study.

DESIGN:

Database study.

PARTICIPANTS:

In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence.

METHODS:

Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed.

MAIN OUTCOME MEASURES:

Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG.

RESULTS:

The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P = 1.0 × 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P = 1.2 × 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P = 1.8 × 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P = 5.9 × 10-10).

CONCLUSIONS:

We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.

Copyright © 2018 American Academy of Ophthalmology. All rights reserved.

PMID:

29433851

DOI:

10.1016/j.ophtha.2018.01.007

Cancer Epidemiol. 2017 Oct;50(Pt A):113-124. doi: 10.1016/j.canep.2017.08.012. Epub 2017 Sep 1.

Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence.

Wright CM1, Moorin RE2, Chowdhury EK3, Stricker BH4, Reid CM5, Saunders CM6, Hughes JD7.

Author information

Abstract

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I2=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I2=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.

KEYWORDS:

Amlodipine; Breast neoplasms; Calcium channel blockers; Dihydropyridines; Nifedipine; Verapamil

J Hypertens. 2015 Jun;33 Suppl 1:e124. doi: 10.1097/01.hjh.0000467686.77672.9e.

9C.05: META-ANALYSIS OF AMLODIPINE VERSUS ANGIOTENSIN RECEPTOR BLOCKERS ON BLOOD PRESSURE, SOME ECHOCARDIOGRAPHIC INDICATORS OF LEFT VENTRICULAR DAMAGE AND ADVERSE EVENTS IN PATIENTS WITH HYPERTENSION.

Xu H1, Wang Q, Yang M, Yu J.

Author information

Abstract

OBJECTIVE:

The aim of this meta-analysis is to evaluate two echocardiographic indicators of left ventricular damage, amlodipine and angiotensin receptor blockers, and associated adverse events in patients with hypertension.

DESIGN AND METHOD:

A meta-analysis was conducted using PubMed, Cochrane Library and EMBASE to investigate and analyze the effects of amlodipine versus angiotensin receptor blockers for blood pressure, associated adverse events, and cardiac structure and function. Data was collected from database inception through October 2014.

RESULTS:

Nineteen randomized-control clinical trials were included in the meta-analysis. 4,248 subjects from the collected trials were given either amlodipine or angiotensin receptor blockers (ARBs) for management of hypertension. The results showed no significant differences between amlodipine and ARBs in ability to lower blood pressure. However, when measuring the decrease of left ventricular mass index (LVMI), amlodipine was shown to be inferior to both irbesartan (weighted mean difference= -15.1, 95% confidence intervals: -22.97 to -7.23, P < 0.001) and valsartan (weighted mean difference = -17.77, 95% confidence intervals:-31.28 to -4.27, P = 0.01). Amlodipine showed decreased performance compared to losartan in early diastolic mitral annular velocity (E[Combining Acute Accent]), the ratio of left ventricular early diastolic filling velocity to early diastolic mitral annular velocity (E/E[Combining Acute Accent]) and an increased number of adverse events[(E[Combining Acute Accent]:weighted mean difference= -0.09, 95%CI -1.76 to -0.04, P = 0.04), (E/E[Combining Acute Accent]:weighted mean difference = 3.00,95%CI 1.22 to 4.78, P = 0.001), (adverse events: OR = 3.78, 95%CI 1.29 to 11.06, P = 0.02)]. Additionally, amlodipine led to more adverse events when compared with valsartan (OR = 1.80, 95% confidence intervals:1.17 to 2.78, P = 0.008).

CONCLUSIONS:

Amlodipine is comparable to several ARBs in its potential to lower blood pressure. However, it is less effective in prevention of left ventricular hypertrophy and exhibits a higher incidence of clinically adverse events, such as dizziness, fatigue, headache, peripheral edema, and erectile dysfunction.

PMID:

26102722

DOI:

10.1097/01.hjh.0000467686.77672.9e

A User’s Guide To Dr. Maloney

(Or, Can I Get This Guy On The Phone?)

Who Am I?

A Naturopathic Doctor, an evidence-based old time doctor who treats with household foods and lifestyle change whenever he can. I look out ten years into the future when I think about my prescriptions.

When Should I See You?

“When you get hit by a bus, go see an M.D. If you just feel like you were, it’s time to see me.” I’d love to see you before you feel that bad, but I understand that most of us are too busy for pain unless it really gets our attention.

Will You Work With My Family Doctor And Specialists?

Yes. No single doctor can be as good as a team.

Will It Cost Me A Lot of Money?

I charge $100 an hour. My visits are one and a half hours, so the cost is $150. BUT...insurance doesn’t cover me, so if you have coverage I will be more expensive.

Privacy Policy

I will maintain your trust and confidentiality in all situations.

Telephone

When you call, you will get voicemail. I can answer your questions easier if you text to my email: docmaloneynd@gmail.com.

Missed appointments

My other patients have asked me to have a policy that requires two days notice if you want to change an appointment. It is so I can help someone else at your time. If you miss an appointment (without an emergency) you will be charged for half the cost of the visit.

Email

I do not respond in the modern sense. Think of sending me an email in the same way you would sending someone else a snail mail. I will get back, but it may take me a few days. Often this is because I want to look something up for you and need time to do so. Thanks for understanding!

Thanks for reading!

Basic Treatment Guidelines (Things I wish I did every day)

One Hundred Abdominal Breaths

Place your hand on your abdomen. Practice filling your belly without lifting your shoulders. Exhale with force, tightening your stomach. Practice at stop lights, in line, etc.

Visualize Healing

Relax. Imagine breathing in light, healing, or relaxation and exhaling dark, pain, or tension. Picture yourself well. How does it feel? Your immune system will respond by lowering inflammation.

Sleep

Establish a routine. Sleep before midnight, in 1 ½ hour segments (normal REM) to awaken rested. (3 hours, 6 hours, 7 ½ hours, etc.)

Movement and Play

Move daily. Do something fun. Imitate your pets, children, or friends. Laughter is essential for stress management and a healthy heart.

Water

Drink until you urinate every two hours. You do not feel thirst until you are two quarts low. End showers with a brief cold to wake up in the morning.

Food

Seek out wonderful food that happens to be healthy. Break your food habits weekly. Variety and color. Do not deprive yourself. Chew thoroughly.

Gut Bugs

We can live in a healthy relationship with ourselves. Cravings may not be from you, especially if they make you feel worse after you eat them. Probiotics are part of a healthy diet.

Liver

Give your liver a break once a month. Avoid carcinogens, excess alcohol, and environmental toxins. Eat dark leafy greens and cultivate a taste for bitter foods that move bile.

Skin

Skin is our largest organ. Brush it lightly toward the heart to help your lymph drain and to stimulate healthy growth.

Financial

Brainstorm to meet your needs. Beyond the essential, think of other things. Serve people and use money, not the other way around.

Social

Surround yourself with positive people. Seek them out. Become one.

Spirit

Cultivate a religion, organized or your own. Practice it every day.

Music

Surround yourself with your own soundtrack. We are all the heroes of our own lives. If this isn’t true yet, change the script.

The Relaxation Response

Dr. Benson describes the practice of the" Relaxation Response" technique as follows:

1. Sit quietly in a comfortable position.

2. Close your eyes.

3. Deeply relax all your muscles, beginning at your feet and progressing up to your face. Keep them relaxed.

4. Breathe through your nose. Become aware of your breathing. As you breathe out, say the word, "ONE," silently to yourself. For example breathe IN... OUT, "ONE; IN...OUT, "ONE", etc. Breathe easily and naturally.

5. Continue for 10 to 20 minutes. You may open your eyes to check the time, but do not use an alarm. When you finish, sit quietly for several minutes, at first with your eyes closed and later with your eyes opened. Do not stand up for a few minutes.

6. Maintain a passive attitude and permit relaxation to occur at its own pace. When distracting thoughts occur, try to ignore them by not dwelling on them and return to repeating "ONE". With practice, the response should come with little effort. Practice the technique once or twice daily, but not within two hours after any meal, since the digestive processes seem to interfere with the elicitation of the Relaxation Response.

Resource: Benson, Herbert, The Relaxation Response, New York: William Morrow and Company, Inc., 1977, p.114]

Anxiety, depression, fatigue, and infertility: statistically significant decreases in anxiety, depression, and fatigue as well as increases in vigor. In addition, 34% of these women became pregnant within 6 months of completing the program. Fertil Steril 1990 Feb;53(2):246-9

SELF THERAPY

Pick something important to you (God, Money, Relationships, Time,)

What is your first memory of this?

How did your parents experience it? What did they teach you?

What negative experiences have you had with this?

How is this holding you back in your life?

How do you move forward? (Problem avoidance/goal setter?)

Write down twenty sentences about this. (_________ is/are…….)

What positive experiences have you had with this?

To what do you attribute those positive experiences?

Go back to your twenty sentences and rewrite them as positive statements about you and your future.

Can you put all twenty sentences into a single positive statement that will act as a goal?

Anti-Inflammatory Diet

Eat only the following organically grown foods for 21 days

Steamed vegetables:

Eat a variety of any and all vegetables that you tolerate. Avoid tomatoes, potatoes, eggplant and bell peppers. Yams, sweet potatoes, and squash are allowed. The primary reason for using steamed vegetables is that steaming improves the utilization or the availability of the food substances and it reduces the irritating residue in the gut, allowing it to restore itself.

Nuts

Any nut that you can tolerate except peanuts (actually a legume).

Legumes

Eat a variety of any legumes you are able to tolerate: split peas, lentils, kidney beans, pinto beans, soybeans, mung beans, garbanzo beans, aduki & azuki beans.

Grains

Eat one to two cups of cooked grains per day of those you tolerate.

Allowed grains are: millet, basmati or brown rice, quinoa, barley, buckwheat, oatmeal, and amaranth. Other grain foods that may be eaten are rice crisps and wasa crackers. In general, plan meals so that bread is not required (rice and beans instead of tacos, celery and nut butter or a chicken salad instead of a sandwich).

Fish

Deep sea fish is preferred (salmon, halibut, cod, sardines, tuna, mackerel - no shellfish or swordfish). The fish should be poached, baked, steamed, or broiled.

Chicken/Turkey

Eat only white meat and do not eat the skin. The chicken should be baked, broiled, or steamed. Free-range or organic chicken is preferable.

Fruit

Eat 1 or 2 pieces of practically any fruit except citrus. Apples, pears, bananas, U.S. grapes, peaches, apricots, mangos, papayas are all acceptable. If possible, bake the fruit for easier digestion.

Sweeteners

Very small amounts of maple syrup, rice syrup, barley syrup and honey may be used.

Absolutely no sugar, Nutrasweet, or any other sweetener is allowed. Often sugar cravings can be avoided by eating protein with each meal.

Butter/Oils

For butter, mix together 1 pound of butter and 1 cup of extra virgin olive oil (from a new dark jar). Whip at room temperature and store in the refrigerator. Provides the benefits and taste of butter and essential fatty acids. Use extra virgin olive oil for all other situations requiring oil.

Herbal teas and good water to drink

Drink 8 to 10 glasses of clean water every day. Drink 2 to 4 cups of herbal tea, sipped slowly in the evening.

For the time-being, avoid the following foods:

Dairy products (milk, cheese, yogurt, kefir). Eggs. Fried foods. Processed foods. Wheat products (breads, muffins, doughnuts, etc.). Corn products (chips, tacos, enchiladas). All caffeinated products. If necessary, wean down with green tea. Alcohol of all kinds. Potatoes, tomatoes, eggplant, green and red bell peppers. Citrus (grapefruit, oranges, lime, lemon). Peanuts and peanut butter (substitute almond butter if necessary). Meat - red meat and especially pork and pork products. Sugar, Nutrasweet, and all sweeteners (except maple syrup and honey)

Week Menu

The biggest change in many diets is in breakfast. Experiment with having "dinner" in the morning, either prepared the night before or made fresh.

B-Oatmeal (add sunflower or flax, dried fruit), L-chicken salad, fruit, D-rice and beans.

B-Protein smoothie (banana, protein powder, other fruit), L-leftover rice and beans, D-baked salmon and salad.

B-alternative grain cereal with soy milk, Snack-almonds, L-california rolls/sushi, D-bean soup.

B-rice and lentils, L-buckwheat soba, D-Indian curry over rice with steamed vegetables.

B-almond butter on rice toast, L- soy cheese on rice crackers, D-chicken with sweet potatoes.

B-spaghetti squash with raisins, maple syrup, and cinnamon. L-split pea soup D-Stir fry.

B-barley soup L-chicken with steamed vegetables D-Thai take out with baked apples (cinnamon and maple syrup) for dessert.

A change in diet means a opening a whole new world. In reexamining our food, we reexamine our past and our present. Unconscious habits, learned early in childhood, become conscious. An unexamined plate is not worth eating.

Home Medicine

What herbs and supplements does Dr. Maloney have on hand for his family? All of the following are available through Full Script/Emerson Ecologics (1-800-654-4432) or you can go on my website. Then find the same brand cheaper elsewhere if you’d like.

Sign up on Fullscript to get these things.

Liquid Calcium Magnesium Orange-Vanilla 2:1

Integrative Therapeutics 16 oz (constipation, bone health, and muscle pains) Product Code: SKU: ITI-10020

It tastes like a bad orange-vanilla milkshake. It keeps my boys regular, and prevents “growing pains”.

LiquiD3 Liquid Rx Vitamins 2000 IU 1 oz Product Code: SKU: RXV-3010

We take 2,000 IU three times a week. Here in the northeast, we don’t get enough D.

S.B.C.(Saccharomyces Boulardii) Douglas Labs 50 caps Product Code: SKU: DL-930250X

Whenever we have a belly upset, we take a probiotic, a non-disease causing yeast, sacchromyces boulardii. It survives antibiotic exposure, but may constipate (see above).

Nordic Berries Gummy Berries Nordic Naturals 120 berries Product Code: SKU: NORD-30120

I have found that Nordic berries can act as both multivitamin and reward for children.

DHA Junior Nordic Naturals 180 gels Product Code: SKU: NORD-03180

Another easy sell is the strawberry flavored fish oil capsule, distilled for purity.

Adults can use: Arctic Omega Lemon Liquid Nordic Naturals Product Code: SKU: NORD-04103

Men Over 40™ One Daily Iron Free Innate Response Product Code: SKU: INR-40125

My multivitamin that I take maybe once a week. Whole food, independently tested.

Women Over 40™ One Daily Innate Response Product Code: SKU: INR-40124

My wife is MUCH more consistent about taking her supplements. But over time, we found that she was getting too much and it was making her ill. The current one works better.

Garlic Extract 300mg Vital Nutrients Product Code: SKU: VN-GE

For cold prevention, garlic contains a low-grade antibiotic/antiviral. 

Sambucus Black Elderberry Syrup Integrative Therapeutics Product Code: SKU: ITI-70653

This is black elderberry in a concentrated form. If I can’t find elderberry jam, I use this in addition to fresh garlic to nip colds in the bud. I also use something I call “toxic sludge,” but it is prescription only. (Throatease Wise Woman Herbals SKU: WWH-2THCO) Ask me for it if you feel yourself coming down with something.

Alive! Rice Pea Shake (vanilla) Boericke & Tafel Product Code: SKU: NW-15545

One scoop in the family smoothie. All your vitamins in a shake.

Sign up on Fullscript to get these things.

These are the things I have on hand for my family. I'm sharing them with you for your consideration.

Liquid Calcium Magnesium Orange-Vanilla 2:1

Integrative Therapeutics 16 oz (constipation, bone health, and muscle pains) Product Code: SKU: ITI-10020

It tastes like a bad orange-vanilla milkshake. It keeps my boys regular, and prevents “growing pains”.

LiquiD3 Liquid Rx Vitamins 2000 IU 1 oz Product Code: SKU: RXV-3010

We take 2,000 IU three times a week. Here in the northeast, we don’t get enough D.

S.B.C.(Saccharomyces Boulardii) Douglas Labs 50 caps Product Code: SKU: DL-930250X

Whenever we have a belly upset, we take a probiotic, a non-disease causing yeast, sacchromyces boulardii. It survives antibiotic exposure, but may constipate (see above).

Nordic Berries Gummy Berries Nordic Naturals 120 berries Product Code: SKU: NORD-30120

I have found that Nordic berries can act as both multivitamin and reward for children.

DHA Junior Nordic Naturals 180 gels Product Code: SKU: NORD-03180

Another easy sell is the strawberry flavored fish oil capsule, distilled for purity.

Adults can use: Arctic Omega Lemon Liquid Nordic Naturals Product Code: SKU: NORD-04103

Men Over 40™ One Daily Iron Free Innate Response Product Code: SKU: INR-40125

My multivitamin that I take maybe once a week. Whole food, independently tested.

Women Over 40™ One Daily Innate Response Product Code: SKU: INR-40124

My wife is MUCH more consistent about taking her supplements. But over time, we found that she was getting too much and it was making her ill. The current one works better.

Garlic Extract 300mg Vital Nutrients Product Code: SKU: VN-GE

For cold prevention, garlic contains a low-grade antibiotic/antiviral. 

Sambucus Black Elderberry Syrup Integrative Therapeutics Product Code: SKU: ITI-70653

This is black elderberry in a concentrated form. If I can’t find elderberry jam, I use this in addition to fresh garlic to nip colds in the bud. I also use something I call “toxic sludge,” but it is prescription only. (Throatease Wise Woman Herbals SKU: WWH-2THCO) Ask me for it if you feel yourself coming down with something.

Alive! Rice Pea Shake (vanilla) Boericke & Tafel Product Code: SKU: NW-15545

One scoop in the family smoothie. All your vitamins in a shake.

Curr Vasc Pharmacol. 2013 Nov;11(6):812-6.

Risk and benefit of statins in stroke secondary prevention.

Laloux P1.

Author information

Abstract

Statin is now recommended in secondary prevention after stroke or transient ischemic attacks to reduce the risk of a new stroke or major cardiovascular events. However, some issues about the extent of the benefit in some stroke patients and the risk of cerebral hemorrhage remain debated. This review shows that statins are significantly effective in decreasing the risk of further strokes despite an increase in the risk of brain hemorrhage. A significant benefit was observed in men and women, in aged patients and possibly to a greater extent in patients with carotid artery stenosis. Intensive statin therapy lowering the LDL-cholesterol beyond the cut-off value of 1.8 mmol/L (70 mg/dl) seems to be more effective than less intensive treatment and without an increased risk of side effects. Overall, statins are well tolerated. Further prospective studies should clarify whether the effect is of the same magnitude in small vessel disease and how to select the patients to reduce the risk of cerebral hemorrhage.

PMID:

24484462

[Indexed for MEDLINE]

BMJ Open. 2015 Feb 25;5(2):e007075. doi: 10.1136/bmjopen-2014-007075.

Statin use and risk of haemorrhagic stroke in a community-based cohort of postmenopausal women: an observational study from the Women's Health Initiative.

Salmoirago-Blotcher E1, Hovey KM2, Andrews CA2, Robinson JG3, Johnson KC4, Wassertheil-Smoller S5, Crawford S6, Qi L7, Martin LW8, Ockene J9, Manson JE10.

Author information

Abstract

OBJECTIVES:

To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.

DESIGN:

Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.

SETTING:

Women were recruited from 40 participating sites.

PARTICIPANTS:

Cohort of 68,132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.

MAIN OUTCOME MEASURES:

Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the 'no use' category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications.

RESULTS:

Final models included 67,882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10,000 person-years among statin users and 5.0/10,000 person-years among non-users (p=0.11). The unadjusted risk of HS in statinusers was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011.

CONCLUSIONS:

This retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

KEYWORDS:

PREVENTIVE MEDICINE

PMID:

25716175

PMCID:

PMC4342587

DOI:

10.1136/bmjopen-2014-007075

[Indexed for MEDLINE] 

Free PMC Article

• Share on Facebook

• Share on Twitter

• Share on Google+

J Stroke Cerebrovasc Dis. 2013 Jan;22(1):66-71. doi: 10.1016/j.jstrokecerebrovasdis.2011.06.008. Epub 2011 Jul 22.

Early statin use is associated with increased risk of infection after stroke.

Becker K1, Tanzi P, Kalil A, Shibata D, Cain K.

Author information

Abstract

BACKGROUND:

Infection after stroke is common and likely detrimental. Given the potent immunomodulatory properties of statins, we hypothesized that early statin use might increase the risk of infection in the immediate post stroke period.

METHODS:

In a study cohort of 112 patients with ischemic stroke, we assessed the impact of early statin use on the risk of post strokeinfection.

RESULTS:

After controlling for stroke severity and patient age, the odds ratio (OR) and 95% confidence interval (CI) for infection in the first 15 days after stroke among patients on a statin by day 3 after stroke was 7.21 (95% CI 1.40-37.98; P = .018). When controlling for univariate predictors of infection, the OR associated for infection associated with statin use actually increased, but was no longer significant (8.49 [95% CI 0.92-77.98]; P = .059). In addition, early statin use was associated with an increase in plasma interleukin-1 receptor antagonist (IL-1ra); IL-1ra was significantly higher in early statin users than in nonstatin users by day 7 after stroke.

CONCLUSIONS:

Our data suggest that early statin use appears to be associated with and increased risk of post stroke infection. This riskmay, in part, be related to increases in plasma IL-1ra. If these findings are replicated in larger studies, they could have important implications for the timing of statin therapy after stroke.

Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

PMID:

21782466

PMCID:

PMC3202647

DOI:

10.1016/j.jstrokecerebrovasdis.2011.06.008

[Indexed for MEDLINE] 

Free PMC Article

J Neurol Sci. 2015 Jan 15;348(1-2):89-93. doi: 10.1016/j.jns.2014.11.013. Epub 2014 Nov 18.

Statin use increases the risk of depressive disorder in stroke patients: a population-based study.

Kang JH1, Kao LT2, Lin HC3, Tsai MC4, Chung SD5.

Author information

Abstract

This study aimed to explore the risk for depressive disorder (DD) among stroke patients with statin use. Totally, 11,218 patients who had a first-time acute hospitalization for stroke were identified from Taiwan's Longitudinal Health Insurance Database 2000. We individually followed each study subject for a 1-year period to identify those patients who were subsequently diagnosed with DD during the follow-up period. We found that the incidence rate of DD during the 1-year follow-up period was 5.52 (95% CI: 4.70-6.43) and 3.46 (95% CI: 3.08-3.88) per 100 person-years for stroke patients who were statin users and nonusers, respectively. Cox proportional hazards regressions revealed that the adjusted hazard ratio (HR) for DD during the 1-year follow-up period was 1.59 for stroke patients who were statin users compared to those who were non-statin users. We further found that the adjusted HR for DD for stroke patients who were regular statin users was 1.65 compared to stroke patients who had never been prescribed statin. However, there was no increased hazard of DD for stroke patients who were irregular statin users compared to stroke patients who had never been prescribed statin (HR: 1.22, 95% CI: 0.70-2.11).

Copyright © 2014. Published by Elsevier B.V.

KEYWORDS:

Cerebrovascular disease; Depression; Depressive disorder; Epidemiology; Statin; Stroke

Comment in

• Letter by Huang regarding the article, "Statin use increases the risk of depressive disorder in stroke patients: A population-based study". [J Neurol Sci. 2015]

PMID:

25483831

DOI:

10.1016/j.jns.2014.11.013

Stroke. 2014 May;45(5):1492-4. doi: 10.1161/STROKEAHA.114.004130. Epub 2014 Apr 8.

Risk factors, stroke prevention treatments, and prevalence of cerebral microbleeds in the Framingham Heart Study.

Romero JR1, Preis SR, Beiser A, DeCarli C, Viswanathan A, Martinez-Ramirez S, Kase CS, Wolf PA, Seshadri S.

Author information

Abstract

BACKGROUND AND PURPOSE:

Cerebral microbleeds (CMBs) are associated with increased risk of stroke and poor cognition. Vascular riskfactors and medications used for stroke prevention may increase the risk of CMB. We examined the prevalence of CMB and the association of these risk factors with CMB, postulating that risk factors for cerebral amyloid angiopathy would be associated with lobar CMB and markers of hypertensive vasculopathy with deep CMB.

METHODS:

We include 1965 Framingham Original and Offspring participants (age, 66.5±11.0 years; 54% women) and evaluated the age- and sex-specific prevalence of CMB. We related various vascular and genetic (apolipoprotein E [APOE]) risk factors and medication use to the presence of CMB overall and stratified by brain location (deep, lobar, or mixed).

RESULTS:

CMBs were observed in 8.8% of participants, being mostly lobar (63%). CMB prevalence increased with age (P<0.0001) and was higher in men (P<0.001). Hypertension increased risk of any CMB, and in deep and mixed locations (P<0.05), and low total cholesterol and APOE ε4 increased risk of lobar CMB (P<0.05). Statin use increased risk of lobar and mixed location CMB (P<0.05). The latter association was not affected by adjustment for cholesterol levels or concomitant medication use.

CONCLUSIONS:

We observed the expected association of hypertension with deep CMB and low cholesterol and APOE ε4 with lobar CMB. In addition, statin use was independently associated with CMB risk. This potential adverse effect of statin use needs to be examined in other cohorts.

KEYWORDS:

cerebral small vessel disease; epidemiology; risk factors

PMID:

24713533

PMCID:

PMC4048617

DOI:

10.1161/STROKEAHA.114.004130

Lancet Neurol. 2009 May;8(5):453-63. doi: 10.1016/S1474-4422(09)70058-4.

Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention.

Amarenco P1, Labreuche J.

Author information

Abstract

Despite the inconsistent or weak association between cholesterol and stroke, lowering of cholesterol concentrations with statins reduces the risk of stroke in high-risk populations and in patients with non-cardioembolic stroke or transient ischaemic attack. Statin therapy is the most important advance in stroke prevention since the introduction of aspirin and antihypertensive treatments. Meta-analysis of randomised trials of statins in combination with other preventive strategies, including 165 792 individuals, shows that each 1 mmol/L (39 mg/dL) decrease in LDL cholesterol equates to a reduction in relative risk for stroke of 21.1% (95% CI 6.3-33.5, p=0.009). In secondary prevention of non-cardioembolic stroke, intense reduction of LDL cholesterol by statins also significantly reduced the risk of recurrent stroke (relative risk 0.84, 0.71-0.99, p=0.03) and major cardiovascular events (0.80, 0.69-0.92, p=0.002). Future directions include assessment of a target LDL cholesterol concentration of less than 1.8 mmol/L (70 mg/dL), the effects of triglyceride-lowering therapy alone or in combination with statins, and the effects of treatments to raise HDL cholesterol concentrations.

PMID:

19375663

DOI:

10.1016/S1474-4422(09)70058-4

PLoS One. 2014 Mar 18;9(3):e92388. doi: 10.1371/journal.pone.0092388. eCollection 2014.

Statins for the prevention of stroke: a meta-analysis of randomized controlled trials.

Wang W1, Zhang B1.

Author information

Abstract

BACKGROUND:

Stroke is a frequently encountered clinical event that has a detrimental impact on the quality of life. Evidence has increasingly shown that statins can substantially reduce the risk of coronary heart disease. However, it remains to be determined whether statins are definitively effective in preventing stroke.

METHODS:

We systematically searched the PubMed, Embase, and Central databases for studies that compared the effects of statins and placebo in patients at high risk for stroke. The outcome measures were overall incidence of stroke, incidence of fatal stroke, and incidence of hemorrhagic stroke.

RESULTS:

Eighteen randomized controlled trials satisfied all the inclusion criteria for the meta-analysis. The analysis revealed that statinsreduced the overall incidence of stroke than placebo (odds ratio [OR]: 0.80; 95% confidence interval [CI]: 0.74-0.87; P<0.00001). In particular, statins showed efficacy in reducing the incidence of fatal stroke (OR: 0.90; 95% CI: 0.67-1.21; P = 0.47) and hemorrhagic stroke (OR: 0.87; 95% CI: 0.60-1.25; P = 0.45). On the contrary, they were found to increase the overall incidence of stroke (OR: 1.12; 95% CI: 0.89-1.41; P = 0.32) and fatal stroke (OR: 1.37; 95% CI: 0.93-2.03; P = 0.11) in renal transplant recipients and patients undergoing regular hemodialysis.

CONCLUSION:

The results of this analysis suggest that statins may be beneficial in reducing the overall incidence of stroke and they may decrease the risk of fatal stroke and hemorrhagic stroke. However, statins should be used with caution in patients with a history of renal transplantation, regular hemodialysis, transient ischemic attack, or stroke. Further analyses should focus on multicentre, double-blind, placebo-controlled randomized trials with data stratification according to the nature of primary diseases and dose-effect relationship, to clarify the benefits of statins in protection against stroke.

PMID:

24643199

PMCID:

PMC3958535

DOI:

10.1371/journal.pone.0092388