Prevalence and determinants of electrocardiographic abnormalities in sub-Saharan African individuals with type 2 diabetes

Aim

This study assessed the prevalence and determinants of electrocardiographic abnormalities in a group of type 2 diabetes patients recruited from two referral centres in Cameroon.

Methods

A total of 420 patients (49% men) receiving chronic diabetes care at the Douala General and Yaoundé Central hospitals were included. Electrocardiographic abnormalities were investigated, identified and related to potential determinants, with logistic regressions.

Results

The mean age and median duration of diagnosis were 56.7 years and four years, respectively. The main electrocardiographic aberrations (prevalence %) were: T-wave abnormalities (20.9%), Cornell product left ventricular hypertrophy (16.4%), arrhythmia (16.2%), ischaemic heart disease (13.6%), conduction defects (11.9%), QTc prolongation (10.2%) and ectopic beats (4.8%). Blood pressure variables were consistently associated with all electrocardiographic abnormalities. Diabetes-specific factors were associated with some abnormalities only.

Conclusions

Electrocardiographic aberrations in this population were dominated by repolarisation, conduction defects and left ventricular hypertrophy, and were more related to blood pressure than diabetes-specific factors.     

Influence of lipophilicity on the diffusion of cephalosporins into the cerebrospinal fluid

Summary— The aim of this quantitative structure-activity relationship (QSAR) study was to investigate the influence of lipophilicity on the diffusion of cephalosporins into the cerebrospinal fluid (CSF). The lipophilicity was expressed as the chromatographic capacity factor (log k'_w) determined by high-performance liquid chromatography in a reversed-phase system. The penetration of eight cephalosporins into CSF was studied in male Wistar rats receiving the drugs intramuscularly (1.5 mg/kg). One hour after administration, CSF and blood samples were collected, and concentrations of free drug were measured in CSF (C_CSF) and in plasma (C_P). A significant parabolic relationship was sought between lipophilicity (log k'_w) and the capacity of diffusion across the blood-brain barrier expressed as log (C_CSF/C_P). The cephalosporins exhibiting a moderate lipophilicity diffused well into CSF. A pharmacokinetic study was performed at 1, 2 and 4 h after administration of three cephalosporins: cefazolin, ceftriaxone and cefsulodin. These compounds were choosen according to their lipophilicities (low, moderate and high values, respectively). The AUC_0–4h for both free plasma (AUC_P) and cerebrospinal fluid (AUC_CSF) concentrations were determined. The AUC_CSF/AUC_P ratio presented a maximum value for a strongly albumin bound cephalosporin, ceftriaxone. In our experimental conditions, the ideal lipophilicity (log k'_w) range for diffusion of cephalosporins from plasma into CSF was between 1.6 and 1.8.     

Osteoporosis: radiographic detection of fluoride-induced extra-axial bone formation

New bone formation in the peripheral skeleton was detected radiographically in 67% (22/33) of patients studied for new periarticular pain among 72 patients with osteoporosis being treated with fluoride, 66-88 mg/d, for 6 or more months. Changes included periosteal and endosteal new bone formation as well as trabecular thickening and were localized in areas of high mechanical stress. Sufficient mineral deposition for radiographic detection required 6 or more months of fluoride treatment. Radiologists must differentiate fluoride-induced new bone formation from other-processes, such as fractures and tumor, and elicit information on fluoride intake in suspicious cases.     

Miniature endplate current rise times less than 100 microseconds from improved dual recordings can be modeled with passive acetylcholine diffusion from a synaptic vesicle.

We recorded miniature endplate currents (mEPCs) using simultaneous voltage clamp and extracellular methods, allowing correction for time course measurement errors. We obtained a 20-80% rise time (tr) of approximately 80 micros at 22 degrees C, shorter than any previously reported values, and tr variability (SD) with an upper limit of 25-30 micros. Extracellular electrode pressure can increase tr and its variability by 2- to 3-fold. Using Monte Carlo simulations, we modeled passive acetylcholine diffusion through a vesicle fusion pore expanding radially at 25 nm x ms(-1) (rapid, from endplate omega figure appearance) or 0.275 nm x ms(-1) (slow, from mast cell exocytosis). Simulated mEPCs obtained with rapid expansion reproduced tr and the overall shape of our experimental mEPCs, and were similar to simulated mEPCs obtained with instant acetylcholine release. We conclude that passive transmitter diffusion, coupled with rapid expansion of the fusion pore, is sufficient to explain the time course of experimentally measured synaptic currents with trs of less than 100 micros.     

Hormone therapy for younger postmenopausal women: how can we make sense out of the evidence?

The Women's Health Initiative (WHI) trials have provided us with valuable information on the effect of hormone therapy (HT) in older postmenopausal women. These results have been generalized to women of all ages, despite the fact that the trials were not powered to evaluate the effect of HT in younger women who initiate treatment shortly after menopause. Pooled data from the WHI and other randomized trials now reveal that HT in younger women is associated with a reduction in coronary heart disease events and total mortality, a benefit that is not seen in older women.