Pilot study of potential barriers to blood pressure control in patients with inadequately controlled hypertension

BACKGROUND: Most people with high blood pressure (BP) are managed in primary care, but BP control is often inadequate. OBJECTIVES: To examine potential barriers to adequate BP control in patients with poorly controlled hypertension. DESIGN: Cross-sectional survey. SETTING: Computerized inner city general practice. PARTICIPANTS: A total of 155 hypertensive patients aged 50-80 years with last recorded BP > or =150/90 mm Hg (or > or =140/85 mm Hg if diabetic). METHODS: Patients were invited to attend a nurse-led clinic where BP was measured according to a standardized protocol and patients were asked to complete a semi-structured questionnaire including lifestyle, compliance with treatment and knowledge about hypertension. Details of BP reviews were obtained from medical records. RESULTS: A total of 110 patients (71%) with a mean age of 65 years attended the nurse-led clinic of whom 27% were of African origin. Of those who attended, 52 (47%) had adequately controlled BP when measured according to protocol. The remaining 58 (53%) had inadequately controlled BP. Of patients on treatment, 94% (83/88) reported taking it at least 6 days a week. Only 9% of patients knew their target BP and only 39% that treatment aims to prevent stroke or heart attack. Patients with diabetes were more likely than those without to have BP > or = audit standard (79% 26/33 versus 42% 32/77, P < 0.001). CONCLUSION: About half of apparently uncontrolled hypertensive patients had BP below target when measured according to standard methods. Reported compliance was good, but patient knowledge of target BP was poor. Patients with diabetes were more likely than those without to have inadequately controlled BP.     

Prevalence and penetrance of HFE mutations in 4865 unselected primary care patients

Two HFE gene mutations, C282Y and H63D, underlie the vast majority of cases of hereditary hemochromatosis. We performed a cross-sectional primary care-based study to determine the allele frequency of the C282Y and H63D mutations and the penetrance of each of the affected genotypes defined by their presence. Patients had previously undergone transferrin saturation (TS) testing. A total of 4865 unselected frozen serum samples were analyzed to determine serum ferritin (SF) levels. Genomic DNA isolated from these samples was analyzed for the C282Y and H63D HFE mutations. Homozygotes for each mutation and compound heterozygotes were evaluated to determine clinical penetrance. The allele frequency of C282Y was 0.0507 among Caucasian and 0.0067 among African Americans; that of H63D was 0.1512 and 0.0263, respectively. TS was > or =55% in 83% of individuals with C282Y/C282Y, 14.5% of C282Y/H63D, and 5% of H63D/H63D; SF was > or =300 microG/L in 42, 9, and 5% of these genotypes, respectively. None of the 12 C282Y homozygotes had cardiac dysfunction or hepatic cirrhosis. Only 9/129 (7%) individuals with the genotypes C282Y/H63D or H63D/H63D had a SF > or =300 microG/L; many had explanations other than iron overload that accounted for this increase. Thus, the prevalence of the common HFE mutations is the same in our population as previously described. TS screening would detect most C282Y homozygotes but not the other two genotypes. The penetrance of C282Y/C282Y is significant. The biochemical penetrance of H63D/H63D and C282Y/H63D is modest and the clinical penetrance is low.     

Snake bites by the jararacucu (Bothrops jararacussu): clinicopathological studies of 29 proven cases in Sao Paulo State, Brazil

The jararacucu, one of the most dreaded snakes of Brazil, southern Bolivia, Paraguay and northeastern Argentina, is a heavily-built pit viper which may grow to a length of 2.2 m. Up to 1000 mg (dry weight) of highly-lethal venom may be milked from its venom glands on a single occasion. It has accounted for 0.8% to 10% of series of snake bites in Sao Paulo State, Brazil. We examined 29 cases of proven jararacucu bites recruited over a 20-year period in two Sao Paulo hospitals. Severe signs of local and systemic envenoming, (local necrosis, shock, spontaneous systemic bleeding, renal failure) were seen only in patients bitten by snakes longer than 50 cm; bites by shorter specimens were more likely to cause incoagulable blood. Fourteen patients developed coagulopathy, six local necrosis (requiring amputation in one) and five local abscesses. Two became shocked and four developed renal failure. Three patients, aged 3, 11 and 65 years, died 18.75, 27.75 and 83 h after being bitten, with respiratory and circulatory failure despite large doses of specific antivenom and intensive-care- unit management. In two patients, autopsies revealed acute renal tubular necrosis, cerebral oedema, haemorrhagic rhabdomyolysis at the site of the bite and disseminated intravascular coagulation. In one survivor with chronic renal failure, renal biopsy showed bilateral cortical necrosis; the patient remains dependent on haemodialysis. Effects of polyspecific Bothrops antivenom were not impressive, and it has been suggested that anti-Bothrops and anti-Crotalus antivenoms should be given in combination.      

Erythrocyte sodium/lithium countertransport and renal lithium clearance in a random sample of untreated middle-aged men

1. It has been proposed that the enhanced erythrocyte Na+/Li+ countertransport observed in many patients with essential hypertension could be a marker of abnormal renal proximal tubular function. We thus investigated the relationship of blood pressure and Na+/Li+ countertransport to an index of proximal tubular function such as renal Li+ clearance. 2. The study was carried out in a sample of 299 untreated male subjects (aged 21-59 years) randomly selected from a population at work. Na+/Li+ countertransport was measured in a representative sub-group of 176 men. 3. We did not detect statistically significant correlation of either blood pressure or Na+/Li+ countertransport (Vmax) with fractional excretion of Li+, while confirming the existence of a significant continuous association of blood pressure and body mass index with Na+/Li+ countertransport (P less than 0.01). 4. A sub-sample of 57 participants belonging to the lowest or the highest quintiles of Na+/Li+ countertransport distribution repeated the Li+ clearance study after moderate Na+ restriction. 5. Although fractional excretions of Na+ and Li+ were reduced on the low Na+ diet (both P less than 0.001), they did not differ significantly between groups. 6. Our results are at variance with the findings of a recent case-control study in a young age group and suggest that further studies are necessary before a conclusion can be drawn as to the suitability of Na+/Li+ countertransport as a marker of Na+ reabsorption in the renal proximal tubule.     

Biallelic variants in CENPF causing a phenotype distinct from Strømme syndrome

Biallelic loss-of-function (LoF) variants in CENPF gene are responsible for Strømme syndrome, a condition presenting with intestinal atresia, anterior ocular chamber anomalies, and microcephaly. Through an international collaboration, four individuals (three males and one female) carrying CENPF biallelic variants, including two missense variants in homozygous state and four LoF variants, were identified by exome sequencing. All individuals had variable degree of developmental delay/intellectual disability and microcephaly (ranging from −2.9 SDS to −5.6 SDS) and a recognizable pattern of dysmorphic facial features including inverted-V shaped interrupted eyebrows, epicanthal fold, depressed nasal bridge, and pointed chin. Although one of the cases had duodenal atresia, all four individuals did not have the combination of internal organ malformations of Strømme syndrome (intestinal atresia and anterior eye segment abnormalities). Immunofluorescence analysis on skin fibroblasts on one of the four cases with the antibody for ARL13B that decorates primary cilia revealed shorter primary cilia that are consistent with a ciliary defect. This case-series of individuals with biallelic CENPF variants suggests the spectrum of clinical manifestations of the disorder that may be related to CENPF variants is broad and can include phenotypes lacking the cardinal features of Strømme syndrome.     

Loading-induced changes in synovial fluid affect cartilage metabolism

The purpose of this study was to determine whether changes in the synovial fluid (SF) induced by in vivo loading can induce an alteration in the metabolic activity of chondrocytes in vitro. Therefore, SF was collected from ponies after a period of box rest and after they had exercise for a week. Normal, unloaded articular cartilage explants were cultured in 20% solutions of these SFs for 4 days and chondrocyte activity was determined by glycosaminoglycan (GAG) turnover. In explants cultured in post-exercise SF, GAG synthesis was enhanced and GAG release was diminished when compared to cultures in pre-exercise SF. SF analysis showed that levels of insulin-like growth factors (IGF- I and IGF-II) tended to be higher in post-exercise SF, while no differences were found in metalloproteinase activity, hyaluronic acid and protein concentrations. This study showed that anabolic effects of joint loading on cartilage are, at least partially, mediated by alterations in the SF.      

The epidemiology of HIV infection in Zambia

Population surveys of health and fertility are an important source of information about demographic trends and their likely impact on the HIV/AIDS epidemic. In contrast to groups sampled at health facilities they can provide nationally and regionally representative estimates of a range of variables. Data on HIV-sero-status were collected in the 2001 Zambia Demographic and Health Survey (ZDHS) and made available in a separate data file in which HIV status was linked to a very limited set of demographic variables. We utilized this data set to examine associations between HIV prevalence, gender, age and geographical location. We applied the generalized geo-additive semi-parametric model as an alternative to the common linear model, in the context of analyzing the prevalence of HIV infection. This model enabled us to account for spatial auto-correlation, non-linear, location effects on the prevalence of HIV infection at the disaggregated provincial level (nine provinces) and assess temporal and geographical variation in the prevalence of HIV infection, while simultaneously controlling for important risk factors. Of the overall sample of 3950, 54% was female. The overall HIV-positivity rate was 565 (14.3%). The mean age at HIV diagnosis for male was 30.3 (SD=11.2) and 27.7 (SD=9.3) for female respectively. Lusaka and Copperbelt have the first and second highest prevalence of AIDS/HIV (marginal odds ratios of 3.24 and 2.88, respectively) but when the younger age of the urban population and the spatial auto-correlation was taken into account, Lusaka and Copperbelt were no longer among the areas with the highest prevalence. Non-linear effects of age at HIV diagnosis are also discussed and the importance of spatial residual effects and control of confounders on the prevalence of HIV infection. The study was conducted to assess the spatial pattern and the effect of confounding risk factors on AIDS/HIV prevalence and to develop a means of adjusting estimates of AIDS/HIV prevalence on the important risk factors. Controlling for important risk factors, such as geographical location (spatial auto-correlation), age structure of the population and gender, gave estimates of prevalence that are statistically robust. Researchers should be encouraged to use all available information in the data to account for important risk factors when reporting AIDS/HIV prevalence. Where this is not possible, correction factors should be applied, particularly where estimates of AIDS/HIV prevalence are pooled in systematic reviews. Our maps can be used for policy planning and management of AIDS/HIV in Zambia.