Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension

BACKGROUND: People from British South Asian communities have an increased risk of mortality from coronary heart disease (CHD). Doxazosin, a selective alpha(1)-adrenergic blocker, in addition to lowering blood pressure, has been shown to have positive effects on glucose metabolism and lipid profiles in patients with hypertension. AIM: We studied doxazosin (1-8 mg) and bendrofluazide (2.5 mg) in patients of British South Asian origin with existing mild to moderate hypertension (doxazosin n = 78; bendrofluazide n = 82), to compare their effects on glucose and lipid metabolism in this group. DESIGN OF STUDY: A 34-week randomised, double-blind, parallel-group, multicentre study. SETTING: Primary care in the UK. METHOD: All doxazosin patients started with an initial dose of 1 mg once daily, titrated to a maximum 8 mg once daily if diastolic blood pressure was >90 mmHg or was not <5 mmHg of the baseline value. The primary efficacy variables were mean glucose and total cholesterol concentrations at week 21. RESULT: Doxazosin reduced glucose, total cholesterol, low-density lipoprotein-cholesterol and triglycerides and increased high-density lipoprotein-cholesterol. There were significant differences between doxazosin and bendrofluazide for glucose concentrations at week 21 (P = 0.029) and week 34 (P = 0.015), total cholesterol at week 21 (P = 0.048) and triglycerides at week 21 (P = 0.047) and week 34 (P = 0.009). There was no significant difference in blood pressure lowering between the two treatments. CONCLUSION: Doxazosin exhibits beneficial effects on glucose concentrations and lipid profile, in particular in lowering triglyceride concentrations in British South Asians. Whether these desirable characteristics translate to improved overall cardiovascular risk requires formal evaluation.     

Cognitive and adaptive outcome in low-grade pediatric cerebellar astrocytomas： evidence of diminished cognitive and adaptive functioning in National Collaborative Research Studies （CCG 9891/POG 9130）.

PURPOSE： Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits ff they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study （1） assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and （2） examined the effect of tumor location and medical complications on cognitive and adaptive functioning. PATIENTS AND METHODS： The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astroeytomas, who underwent only surgical treatment as part of Children＇s Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location： vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. RESULTS： The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. CONCLUSION： We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.     

Experimental autoimmune myasthenia gravis induction in B cell-deficient mice

Experimental autoimmune myasthenia gravis (EAMG) is an animal model for human myasthenia gravis (MG). Autoantibody-induced functional loss of nicotinic acetylcholine receptor (AChR) at the postsynaptic membrane is an important pathogenic feature of both MG and EAMG. To evaluate the extent at which the humoral immune response against AChR operates in the pathogenesis of EAMG, we immunized B cell knockout (muMT) and wild- type C57BL/6 mice with AChR and complete Freund's adjuvant. The ability of AChR-primed lymph node cells to proliferate and secrete IFN-gamma in response to AChR and its dominant peptide alpha146-162 were intact in muMT mice as in wild-type mice. Similar amounts of mRNA for IFN-gamma, IL-4 and IL-10 in AChR-reactive lymph node cells were detected in muMT and wild-type mice. However, muMT mice had no detectable anti-AChR antibodies and remained completely free from clinical EAMG. We conclude that B cells are critically required for the genesis of clinical EAMG, but not for AChR-specific T cell priming.      

SMART: Self-Management of Anticoagulation,a Randomised Trial [ISRCTN19313375]

Background  

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care.     

Low dose short duration pulsed electromagnetic field effects on cultured human chondrocytes: An experimental study

Background:

Pulsed electromagnetic field (PEMF) is used to treat bone and joint disorders for over 30 years. Recent studies demonstrate a significant effect of PEMF on bone and cartilage proliferation, differentiation, synthesis of extracellular matrix (ECM) and production of growth factors. The aim of this study is to assess if PEMF of low frequency, ultralow field strength and short time exposure have beneficial effects on in-vitro cultured human chondrocytes.

Materials and Methods:

Primary human chondrocytes cultures were established using articular cartilage obtained from knee joint during joint replacement surgery. Post characterization, the cells were exposed to PEMF at frequencies ranging from 0.1 to 10 Hz and field intensities ranging from 0.65 to 1.95 μT for 60 min/day for 3 consecutive days to analyze the viability, ECM component synthesis, proliferation and morphology related changes post exposure. Association between exposure doses and cellular effects were analyzed with paired''t’ test.

Results:

In-vitro PEMF exposure of 0.1 Hz frequency, 1.95 μT and duration of 60 min/day for 3 consecutive days produced the most favorable response on chondrocytes viability (P < 0.001), ECM component production (P < 0.001) and multiplication. Exposure of identical chondrocyte cultures to PEMFs of 0.65 μT field intensity at 1 Hz frequency resulted in less significant response. Exposure to 1.3 μT PEMFs at 10 Hz frequency does not show any significant effects in different analytical parameters.

Conclusions:

Short duration PEMF exposure may represent a new therapy for patients with Osteoarthritis (OA).     

查耳酮类化合物对过敏性慢反应物质拮抗作用的构效关系

查耳酮类化合物对过敏性慢反应物质拮抗作用的构效关系何克勤，程桂芳，奚凤德，郭宗儒，朱秀媛（中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）过敏性慢反应物质（ＳＲＳＡ），主要含白三烯Ｃ４（ＬＴＣ４）、白三烯Ｄ４（ＬＴＤ４）和白三烯Ｅ４（Ｌ...     

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications.