March 27, 2015

Chronic Kidney Disease & Intensive Glycemic Control Increases Cardiovascular Risk in Patients with Type 2 Diabetes

Shaylma Salinas '15

26 million American adults have chronic kidney disease (CKD) and millions of others are at increased risk. CKD is the gradual loss of kidney function and structure over time. There are five stages of CKD, ranging from mild to moderate to severe. Type II diabetes is when your body is unable to use insulin properly, known as insulin resistance. Type II diabetes is the leading cause of CKD. This form of diabetes associates with increased cardiovascular and mortality risk, but how chronic kidney disease contributes to these risks among individuals with type II diabetes is not completely understood. Ideally the progression of renal damage in diabetes can be slowed through intensive glycemic control and optimization of blood pressure. However, this study shows that individuals with diabetes and CKD have a much higher cardiovascular and mortality risk in comparison to individuals with diabetes and no CKD. The purpose of this study was to assess the impact on cardiovascular outcomes in this population. Data was collected from 10,136 patients with diabetes. Of those, 6,506 were free of CKD and 3,636 met the criteria for CKD. Participants were randomly assigned to a treatment method of either intensive or standard glycemic goal. The primary outcome, all-cause and cardiovascular mortality, and secondary outcomes were analyzed. Risk for the primary outcome was 87% higher in patients with than in those without CKD All secondary outcomes were 1.5 to 3 times more frequent in patients with than in those without CKD. In patients with CKD, compared with standard therapy, intensive glucose lowering was significantly associated with both 31% higher all-cause mortality 41% higher cardiovascular mortality. No significant effects were found in patients without CKD. Thus, in high-risk patients with type II diabetes, mild and moderate CKD is associated with increased cardiovascular risk. Intensive glycemic control significantly increases the risk of cardiovascular and all-cause mortality in this population.

Osteochondritis Dissecans: A disorder of the Epiphysis

Dami Oshin '15

The skeletal system is responsible for the balance and structure of the human body. Abnormalities and variation in the growth patterns of this system could be benign or detrimental depending on its location. Osteochondritis Dissecans (OCD) is a disorder of the epiphysis in the long bones. This disorder occurs when cartilage and subchondral bone becomes loose. Untreated OCD lesions lead to extreme pain and early degenerative arthritis. Due to the weight bearing characteristic, OCD lesions are usually seen in the distal epiphysis of the femur. The cause of OCD is unknown; hence treatments are not completely effective. There are two types of OCD. Adult OCD occurs after skeletal maturity while juvenile OCD occurs before skeletal maturity. In this study, researchers aimed to determine the point at which a disruption in the growth pattern of endochondral ossification leads to OCD lesions. The study used MRI examinations to analyze 30 children with OCD in comparison to 30 children without this condition. A chi square test was employed to compare the integrity of the secondary physis and the chondroepihyseal integrity. Results showed that all children where skeletally immature. A statistically significant difference in the continuity of the secondary physis was observed (p<0.001). No statistically significant difference in the integrity of the chondroepiphysis, however there was a difference in the width of the chondroepiphysis (p<0.001). There was also a significant difference in the bone marrow edema pattern between both groups (p<0.001). The findings of the study suggest that an insult in the normal process of endochondral ossification leads to a disturbance in the secondary physis, leading to Osteochondritis Dissecans.

Decreased Cocaine Use & Addiction in Male Offspring of Cocaine-Using Sires

Dan Jaeger '15

There is an increasing need to understand the reasoning behind drug abuse and, more specifically, how drug abuse is inherited from one generation to the next. Cocaine in particular has caused thousands of deaths per year and untold costs to the health care system. To explore possible epigenetic inheritance of cocaine abuse, Vassoler et al. set up a rat model allowing male rats to self-administer cocaine prior to siring offspring. After the progeny of these cocaine using sires grew to 60 days of age, they were also allowed to self-administer cocaine. These data were then compared to a saline-sired control group's use of cocaine. The cocaine-sired male offspring showed a significant delay in the acquisition of cocaine use as well as decreased maintenance of cocaine use compared to the control group. However, female progeny showed no change in either of these categories. The brains of the cocaine-sired rats were then examined and male brains showed an increase in brain-derived neurotrophic factor levels in the medial prefrontal cortex (mPFC). There was also an increase in the association between acetylated histone H3 and the BDNF promotor of the cocaine using sires sperm as well as in the cocaine-sired males' mPFC. Vassoler et al. concluded that voluntary self-administration of cocaine in male sires leads to reprogramming of the germline resulting in the inheritance of a cocaine resistant phenotype in male offspring as a result of changes in the BDNF levels and expression in the mPFC.