A meta-analysis of genome-wide linkage scans for hypertension: the National Heart,Lung and Blood Institute Family Blood Pressure Program

bACKGROUND: Four multicenter Networks (GenNet, GENOA, HyperGEN, SAPPHIRe) form the National Heart, Lung and Blood Institute Family Blood Pressure Program (FBPP), to search for hypertension/blood pressure (BP) genes. The networks used different family designs and targeted multiple ethnic groups, using standardized protocols and definitions. Linkage genome scans were done on samples within each network (N = 6245 relatives). METHODS: The evidence was synthesized using meta-analysis. RESULTS: Combining ethnic groups, no region reached LOD >2, but several small peaks were identified, including chromosome 2p where two other recent reports find hypertension linkage. CONCLUSIONS: No regions show uniformly large effects on BP/hypertension in all populations.     

The 2004 Canadian recommendations for the management of hypertension: Part III--Lifestyle modifications to prevent and control hypertension

OBJECTIVE: To provide updated, evidence-based recommendations regarding the role of lifestyle modification in the treatment and prevention of hypertension. OUTCOMES: Lifestyle modification interventions including exercise, weight reduction, alcohol consumption, dietary modification, intake of dietary cations and stress management are reviewed. Antioxidants and fish oil supplements are also reviewed, although specific recommendations cannot be made at present. EVIDENCE: MEDLINE searches were conducted from January 2002 to September 2003 to update the 2001 recommendations for the management of hypertension. Supplemental searches in the Cochrane Collaboration databases were also performed. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently using prespecified levels of evidence by content and methodology experts. RECOMMENDATIONS: Key recommendations include the following: lifestyle modification should be extended to nonhypertensive individuals who are at risk for developing high blood pressure; 30 min to 45 min of aerobic exercise should be performed on most days (four to five days) of the week; an ideal body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) should be maintained and weight loss strategies should use a multidisciplinary approach; alcohol consumption should be limited to two drinks or fewer per day, and weekly intake should not exceed 14 standard drinks for men and nine standard drinks for women; a reduced fat, low cholesterol diet that emphasizes fruits, vegetables and low fat dairy products, and maintains an adequate intake of potassium, magnesium and calcium, should be followed; salt intake should be restricted to 65 mmol/day to 100 mmol/day in hypertensive individuals and less than 100 mmol/day in normotensive individuals at high risk for developing hypertension; and stress management should be considered as an intervention in selected individuals. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. Individuals with irreconcilable competing interests (declared by all members, compiled and circulated before the meeting) relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving at least 70% consensus are reported here. These guidelines will continue to be updated annually.     

Colchicine

The clinical pharmacology of colchicine has been reviewed and its therapeutic use described. There is still some disagreement about its diagnostic utility; it is clearly most effective in acute gout, but benefit has been reported from its use in sarcoid arthritis and in the inflammation associated with hydroxyapatite deposition.Colchicine toxicity is largely gastrointestinal in customary doses, with a choleriform syndrome of varying severity produced in 80% of patients. Larger doses in addition produce disseminated intravascular coagulation, marrow failure, hepatocellular failure, and late central-nervous-system dysfunction, among other effects. Treatment of colchicine toxicity is supportive.Colchicine metabolic studies demonstrate that the drug leaves the blood rapidly and remains in cells for protracted periods of time. Measurable amounts were still found in leukocytes as late as 10 days after a single administration, and urinary excretion persisted for a similar length of time.A comparison of the relation between function and the structure of colchicine and its analogues in the human and in two species of rodent revealed significant variability in results. It was concluded that urate crystal-induced inflammation in the rodent was not necessarily a suitable model for human acute gout.Studies of colchicine's mechanism of action in acute gout have previously suggested that it depended on interference with microtubular subunit protein aggregation. Evidence is here summarized that colchicine may have other effects on the cell and that the benefit in gout may possibly be unrelated to the microtubular action.     

Rationale and design of a randomized trial to assess the effects of beta-blocker in diastolic heart failure; Japanese Diastolic Heart Failure Study (J-DHF)

BACKGROUND: Heart failure consists of two phenotypes: systolic heart failure and diastolic heart failure (DHF). A growing body of evidence demonstrated benefits of beta-blocker, angiotensin-converting enzyme inhibitor, and angiotensin II receptor blocker in systolic heart failure; however, evidence leading to therapeutic strategy of DHF is lacking. METHODS AND RESULTS: The Japanese Diastolic Heart Failure Study (J-DHF) is a multicenter, prospective, randomized trial designed to assess effects of beta-blocker in patients with DHF. A total of 800 patients (400 patients in each group) will be enrolled. The primary outcome is a composite of cardiovascular death and unplanned admission to hospital for congestive heart failure. Other outcomes include all-cause mortality, worsening of the symptoms of heart failure, or a need for modification of the treatment for heart failure. Serial assessment of echocardiographic and neurohumoral parameters and cost analysis of the treatment regimen will be conducted. The follow-up period is a minimum of 2 years. CONCLUSION: This study will provide important evidences for the treatment of DHF.     

ASCO-Update 2005--Highlights of the 41st Meeting of the American Society of Clinical Oncology/ASCO 2005

Currently, the treatment of gastrointestinal cancers is rapidly changing due to the implementation of novel chemotherapeutic agents as well as the introduction of targeted therapies into treatment protocols. The following review provides an overview of the most important clinical trials in esophageal, gastric, colorectal, pancreatic and hepatobiliary cancer that were presented at the annual meeting of the American Society of Clinical Oncology.     

Screening, diagnosis and management of early syphilis in genitourinary medicine clinics in the UK

New diagnoses of syphilis in the UK increased eight-fold between 1997 and 2002. This study, conducted in 2002, demonstrated that 31% of clinics were not confident of their expertise to obtain an adequate specimen for dark ground microscopy (DGM), and 35% were not confident of their expertise to detect treponemes on DGM. In all, 64% of clinics had observed adherence problems in HIV-positive patients treated with parenteral regimens, as against 42% with oral regimens. Also, 51% of clinics waited more than a week for the results of initial serological tests for syphilis, and 88% of clinics waited more than a week for confirmatory test results. Other concerns include the failure to perform syphilis serology consistently whenever HIV-positive patients were at risk, and the widespread use of doxycycline as a therapy for syphilis in HIV-positive patients despite concerns that this is not known to be fully treponemicidal in cerebrospinal fluid.