Relating smoking, obesity, insulin resistance, and ovarian biomarker changes to the final menstrual period

To determine if smoking, obesity, and insulin resistance mediated age at final menstrual period (FMP), we examined anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH) as biomarkers of changing follicle status and ovarian aging. We performed a longitudinal data analysis from a cohort of premenopausal women followed to their FMP. Our results found that smokers had an earlier age at FMP ( P < 0.003) and a more rapid decline in their AMH slope relative to age at FMP ( P < 0.002). Smokers had a lower baseline inhibin B level relative to age at the FMP than nonsmokers ( P = 0.002). Increasing insulin resistance was associated with a shorter time to FMP ( P < 0.003) and associations of obesity and time to FMP were observed ( P = 0.004, in model with FSH). Change in ovarian biomarkers did not mediate the time to FMP. We found that smoking was associated with age at FMP and modified associations of AMH and inhibin B with age at FMP. Insulin resistance was associated with shorter time to FMP independent of the biomarkers. Interventions targeting smoking and insulin resistance could curtail the undue advancement of reproductive aging.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79293/1/j.1749-6632.2010.05523.x.pd

Renalase Gene Polymorphisms in Patients With Type 2 Diabetes, Hypertension and Stroke

Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33–2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke

Minimally invasive surgery for diabetic plantar foot ulcerations

Complications of diabetes mellitus constitute the most common indications for hospitalization and non-traumatic amputations in the USA. The most important risk factors for the development of diabetic foot ulcerations include the presence of peripheral neuropathy, vasculopathy, limited joint mobility, and pre-existing foot deformities. In our study, 500 diabetic patients treated for plantar forefoot ulcerations were enrolled in a prospective study from 2000 to 2008 at the Federal University of São Paulo, Brazil. Fifty-two patients in the study met the criteria and underwent surgical treatment consisting of percutaneous Achilles tendon lengthening to treat plantar forefoot ulcerations. The postoperative follow-up demonstrated prevention of recurrent foot ulcerations in 92% of these diabetic patients that maintained an improved foot function. In conclusion, our study supports that identification and treatment of ankle equinus in the diabetic population may potentially lead to decreased patient morbidity, including reduced risk for both reulceration, and potential lower extremity amputation

Diabetes and cardiovascular disease: A statement for healthcare professionals from the American Heart Association

This statement examines the cardiovascular complications of diabetes mellitus and considers opportunities for their prevention. These complications include coronary heart disease (CHD), stroke, peripheral arterial disease, nephropathy, retinopathy, and possibly neuropathy and cardiomyopathy. Because of the aging of the population and an increasing prevalence of obesity and sedentary life habits in the United States, the prevalence of diabetes is increasing. Thus, diabetes must take its place alongside the other major risk factors as important causes of cardiovascular disease (CVD). In fact, from the point of view of cardiovascular medicine, it may be appropriate to say, “diabetes is a cardiovascular disease.

Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier

<p>Abstract</p> <p>Background</p> <p>Methotrexate (MTX) uptake is mediated by the reduced folate carrier (RFC). Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied.</p> <p>Methods</p> <p>In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8), including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines.</p> <p>Results</p> <p>A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, <it>p </it>< 0.05) was identified between the promoter methylation and RFC mRNA levels in this a panel of malignant cell lines.</p> <p>Conclusion</p> <p>This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription.</p

Renal function during rofecoxib therapy in patients with metastatic cancer: retrospective analysis of a prospective phase II trial

German Clinical Trials Register DRKS: DRKS0000011

Active, but not passive cigarette smoking was inversely associated with mammographic density

The opposing carcinogenic and antiestrogenic properties of tobacco smoke may explain why epidemiologic studies have not consistently reported positive associations for active smoking and breast cancer risk. A negative relation between mammographic density, a strong breast cancer risk factor, and active smoking would lend support for an antiestrogenic mechanism. We used multivariable linear regression to assess the associations of active smoking and secondhand smoke (SHS) exposure with mammographic density in 799 pre- and early perimenopausal women in the Study of Women’s Health Across the Nation (SWAN). We observed that current active smoking was associated with 7.2% lower mammographic density, compared to never active smoking and no SHS exposure (p = 0.02). Starting to smoke before 18 years of age and having smoked ≥20 cigarettes/day were also associated with statistically significantly lower percent densities. Among nulliparous women having smoked ≥20 cigarettes/day was associated with 23.8% lower density, compared to having smoked ≤9 cigarettes/day (p &lt; 0.001). Our findings support the hypothesis that tobacco smoke exerts an antiestrogenic effect on breast tissue, but counters the known increased risk of breast cancer with smoking prior to first full-term birth. Thus, our data suggest that the antiestrogenic but not the carcinogenic effects of smoking may be reflected by breast density

Association between CYP19 gene SNP rs2414096 Polymorphism and polycystic ovary syndrome in Chinese women

<p>Abstract</p> <p>Background</p> <p>Several studies have reported the association of the SNP rs2414096 in the CYP19 gene with hyperandrogenism, which is one of the clinical manifestations of polycystic ovary syndrome (PCOS). These studies suggest that SNP rs2414096 may be involved in the etiopathogenisis of PCOS. To investigate whetherthe CYP19 gene SNP rs2414096 polymorphism is associated with the susceptibility to PCOS, we designed a case-controlled association study including 684 individuals.</p> <p>Methods</p> <p>A case-controlled association study including 684 individuals (386 PCOS patients and 298 controls) was performed to assess the association of SNP rs2414096 with PCOS. Genotyping of SNP rs2414096 was conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method that was performed on genomic DNA isolated from blood leucocytes. Results were analyzed in respect to clinical test results.</p> <p>Results</p> <p>The genotypic distributions of rs2414096 (GG, AG, AA) in the CYP19 gene (GG, AG, AA) in women with PCOS (0.363, 0.474, 0.163, respectively) were significantly different from that in controls (0.242, 0.500, 0.258, respectively) (<it>P </it>= 0.001). E2/T was different between the AA and GG genotypes. Age at menarche (AAM) and FSH were also significantly different among the GG, AG, and AA genotypes in women with PCOS (P = 0.0391 and 0.0118, respectively). No differences were observed in body mass index (BMI) and other serum hormone concentrations among the three genotypes, either in the PCOS patients or controls.</p> <p>Conclusions</p> <p>Our data suggest that SNP rs2414096 in the CYP19 gene is associated with susceptibility to PCOS.</p

Antihypertensive medication prescription patterns and time trends for newly-diagnosed uncomplicated hypertension patients in Taiwan

<p>Abstract</p> <p>Background</p> <p>Knowledge of existing prescription patterns in the treatment of newly-diagnosed hypertension can provide useful information for improving clinical practice in this field. The aims of this study are to determine the prescription patterns and time trends for antihypertensive medication in newly-diagnosed cases of uncomplicated hypertension in Taiwan and to compare these with current clinical guidelines.</p> <p>Methods</p> <p>A total of 6,536 newly-diagnosed patients with uncomplicated hypertension, aged ≥30 years, were identified from the representative 200,000-person sample in the computerized reimbursement database of the National Health Insurance in Taiwan. These patients were followed from 1998 to 2004 with all diagnoses, prescription data and medication charges being retrieved for subsequent analysis.</p> <p>Results</p> <p>Prescription patterns varied by age, gender and clinical facilities, with mono-therapies being found to be dominant in the first year, albeit declining over time. Calcium channel blockers and beta-blockers were the most frequently prescribed antihypertensive drugs, either alone or in combinations. Although least expensive, the prescription rates of diuretics were low, at 8.3% for mono-therapies and 19.9% overall. The prescription rate for angiotensin receptor blockers (ARBs) was elevated considerably over time. After controlling for other related factors by multiple logistic regression analysis, ARBs were found to be prescribed mainly by medical centers or regional hospitals.</p> <p>Conclusion</p> <p>These findings indicate the existence of a gap between current clinical practice and the desired goal of cost-effectiveness in antihypertensive treatment in Taiwan, which should be corrected.</p