The differences between the two primary care practitioner groups may reflect variations in training, skills and practice. Further investigation of the particular strengths of both groups, and how they can be optimised to promote effective shared care, is required.
Background Association between the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and congenital heart disease (CHD) is contentious. Methods and Results We compared genotypes between CHD cases and controls, and between mothers of CHD cases and controls. We placed our results in context by conducting metaanalyses of previously published studies. Among 5,814 cases with primary genotype data and 10,056 controls, there was no evidence of association between MTHFR C677T genotype and CHD risk (OR 0.96 [95% CI 0.87-1.07]). A random-effects meta-analysis of all studies (involving 7,697 cases and 13,125 controls) suggested the presence of association (OR 1.25 [95% CI 1.03-1.51]; p=0.022), but with substantial heterogeneity among contributing studies (I2=64.4%), and evidence of publication bias. Meta-analysis of large studies only (defined by a variance of the log OR less than 0.05), which together contributed 83% of all cases, yielded no evidence of association (OR 0.97 [95% CI 0.91-1.03]), without significant heterogeneity (I2=0). Moreover, meta-analysis of 1,781 mothers of CHD cases (829 of whom were genotyped in this study) and 19,861 controls revealed no evidence of association between maternal C677T genotype and risk of CHD in offspring (OR 1.13 [95% CI 0.87-1.47]). There was no significant association between MTHFR genotype and CHD risk in large studies from regions with different levels of dietary folate. Conclusions The MTHFR C677T polymorphism, which directly influences plasma folate levels, is not associated with CHD risk. Publication biases appear to substantially contaminate the literature with regard to this genetic association.
Most UK hospitals, laboratories, and research institutions use uniform reference intervals (RI) that do not take into account known diurnal and racial variation in total white blood cells (WBC) count and its constituent parameters. These risks of excluding potentially suitable ethnic minority volunteers from participating in phase I clinical trials could call into question the validity of a trial's findings or limit its scientific applications and ability to accurately observe drug effects upon WBC parameters. This study pools data from multiple phase I trials, assesses the effects of race and time of day on WBC count, and compares it to the existing literature to establish race and time-specific RIs. A total 13,332 venous blood samples obtained from 7,157 healthy male and female volunteers at the time of screening or admission (predosing) who took part in 35 phase I trials over a period of seven years were pooled and the data were analyzed using generalised estimating equation models. Adjusted RI of total WBC count and its individual parameters were then calculated according to time of day (morning vs. evening) for both black and nonblack populations. This study indicates that black individuals on average had lower total WBC, neutrophil, monocyte, eosinophil, and basophil counts than individuals from nonblack racial groups. Black volunteers had higher mean lymphocyte counts relative to their nonblack counterparts. These differences were deemed statistically significant. Statistically significant increases in total WBC, neutrophil, lymphocyte, and monocyte counts were also observed over the course of daily sampling. Eosinophil counts decreased during this time period, but this finding was only statistically significant in the nonblack population. Despite an observed mild diurnal increase in basophil count in both populations, this was not considered statistically significant. This high-powered study adds significant weight to the known evidence for diurnal and racial variation in WBC parameters. Importantly, it proposes specific RIs that more precisely reflect race and time of day. These could ensure increased participation of black volunteers in clinical trials for improved population representation. Furthermore, the proposed RIs allow for more
BackgroundThis study aimed to estimate the rate of HER-2/neu (c-erbB2) immunohistochemical overexpression in different histological types of breast cancer found in the middle Euphrates region of Iraq, a region that was exposed to high levels of depleted uranium. HER-2/neu (c-erbB2) overexpression was correlated with common clinicopathological parameters such as age, grade, stage, tumor size and lymph node involvement to determine if any particular biomarker for exposure to depleted uranium could be found in the tumor samples from this region.Materials and MethodsThe present investigation was performed over a period starting from September 2007 to June 2008. Formalin-fixed, paraffin-embedded blocks from 90 patients with breast cancer were included in this study. A group of 25 patients with benign breast lesions (fibroadenoma) was included as a comparative group, and 20 breast tissue sections were used as controls. Labeled streptavidin-biotin (LSAB) complex method was employed for immunohistochemical detection of HER-2/neu.ResultsHER-2/neu immuno-expression was positive in 67.8% of breast cancer, while it was negative in all benign breast lesions (fibroadenoma) (P < 0.05). HER-2/neu immunostaining was significantly associated with histological type and recurrence of breast cancer (P < 0.05). It was positively correlated with tumor grade, but this finding was not significant (P > 0.05).ConclusionBased upon the findings of this study, it can be concluded that HER-2/neu overexpression plays an important role in the pathogenesis of breast cancer and is associated with a worse prognosis. The findings indicate that in regions exposed to high levels of depleted uranium, HER-2/neu overexpression is high, but its correlation with age, grade, stage, tumor size, and lymph node involvement is similar to studies that have been conducted on populations not exposed to depleted uranium.
Anything that engenders a homeostatic response in the tightly regulated hypothalamic-pituitary-adrenal (HPA) axis may be thought of as a stressor and may exert an allostatic load, engendering a sustained change in the regulation of this system. Genetic, epigenetic, endocrine, post mortem, and animal studies suggest that dysregulation of the HPA axis plays a part in the pathophysiology of mood disorders and negatively impacts the antidepressant response and prognosis. Neuropsychological impairment, which is a common and disabling concomitant of depression, has been linked to disturbance of the HPA axis. A number of HPA axis-mediated treatment strategies have shown benefit in open or smallscale preliminary trials, and there are ongoing studies seeking both to replicate these initial findings and to develop new targets. HPA axis-based treatments are a fertile area of research, and much current thought pertains to the optimum targets, optimum population (including the potential for stratified medicine), and optimum outcome measures. We have, for instance, argued here that neuropsychological performance may be more sensitive and robust than scores on traditional depression rating scales.
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