The 2001 Canadian recommendations for the management of hypertension: Part one--Assessment for diagnosis, cardiovascular risk, causes and lifestyle modification.

Objective: To provide updated, evidence-based recommendations for the assessment of the diagnosis, cardiovascular risk, identifiable causes and lifestyle modifications for adults with high blood pressure.

Options: For persons in whom a high blood pressure value is recorded, hypertension is diagnosed based on the appropriate measurement of blood pressure, the level of the blood pressure elevation and the duration of follow-up. In addition, the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases must be assessed to determine the urgency, intensity and type of treatment.

Functional tests for primary aldosteronism: value of captopril suppression.

With the introduction of more simple screening tests such as the aldosterone/renin ratio, the detection rate of primary aldosteronism has increased considerably. Until now, no reference values have been available for reporting the aldosterone/renin ratio using plasma aldosterone values expressed in SI units (pmol/L) and plasma active renin (ng/L) measured by immunoradiometric assay. We studied 153 subjects who had either normal blood pressure, essential hypertension, or primary aldosteronism.

Direct interaction between uracil-DNA glycosylase and a proliferating cell nuclear antigen homolog in the crenarchaeon Pyrobaculum aerophilum.

Proliferating cell nuclear antigen (PCNA) acts as a sliding clamp on duplex DNA. Its homologs, present in Eukarya and Archaea, are part of protein complexes that are indispensable for DNA replication and DNA repair. In Eukarya, PCNA is known to interact with more than a dozen different proteins, including a human major nuclear uracil-DNA glycosylase (hUNG2) involved in immediate postreplicative repair.

The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers.

Aims: To examine the effect of concomitant cimetidine or antacid administration on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers in two open-label, randomized studies.

Methods: The first study was a parallel-group design in which 22 healthy male volunteers received sildenafil (50 mg) on days 1 and 5 and cimetidine (800 mg) or placebo on days 3, 4, 5, and 6. Blood samples were collected predose and at specified times up to 48 h postdose on days 1 and 5 to determine plasma levels of sildenafil and its metabolite, UK-103,320.

Nontuberculous mycobacterial adenitis of the head and neck in children: experience from a tertiary care pediatric center.

Objective: To describe our experience with the diagnosis, surgical treatment, and outcome of nontuberculous mycobacterial (NTM) adenitis of the head and neck in children, and to present a preliminary report about the use of NTM skin tests in our institution.

Study Design: Retrospective study.

Methods: The medical records of all children diagnosed with cervicofacial NTM adenitis were retrospectively reviewed for the period from January 1, 1995, through December 31, 2000.

The 2000 Canadian recommendations for the management of hypertension: part two--diagnosis and assessment of people with high blood pressure.

Objective: To provide updated, evidence-based recommendations for the diagnosis and assessment of high blood pressure in adults.

Options: For people with high blood pressure, the assignment of a diagnosis of hypertension depends on the appropriate measurement of blood pressure, the level of the blood pressure elevation, the duration of follow-up and the presence of concomitant vascular risk factors, target organ damage and established atherosclerotic diseases. For people diagnosed with hypertension, defining the overall risk of adverse cardiovascular outcomes requires laboratory testing, a search for target organ damage and an assessment of the modifiable causes of hypertension.

Increased frequency of DNA deletions in pink-eyed unstable mice carrying a mutation in the Werner syndrome gene homologue.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by genomic instability and the premature onset of a number of age-related diseases, including cancers. Accumulating evidence indicates that the WS gene product is involved in resolving aberrant DNA structures that may arise during the process of DNA replication and/or transcription. To estimate the frequency of DNA deletions directly in the skin of mouse embryos, mice with a deletion of part of the murine WRN helicase domain were created.

Efficacy and safety of clarithromycin versus erythromycin for the treatment of pertussis: a prospective, randomized, single blind trial.

Background: Pertussis is still a prevalent public health problem, and antibiotic therapy may decrease disease severity and limit communicability. Erythromycin is the recommended antibiotic for treatment and prophylaxis of pertussis; however, side effects of erythromycin limit its usefulness in some patients. Clarithromycin, a newer macrolide, has good in vitro activity against Bordetella pertussis and a better side effect profile.

Blood pressure-independent effect of angiotensin AT1 receptor blockade on renal endothelin-1 production in hypertensive uremic rats.

Objective: We recently reported that treatment of uremic rats with reduced renal mass with the angiotensin II (Ang II) subtype 1 receptor (AT1) antagonist losartan reduces endothelin-1 (ET-1) levels in blood vessels and in glomeruli. Although this suggests an important role for Ang II in the modulation of ET-1 production, the concomitant decrease in blood pressure may also be involved. The present study was designed to investigate whether the modulation of ET-1 production in uremic rats is related to tissue-specific effects of AT1 receptor blockade or to the antihypertensive effect of losartan.

Werner syndrome: genetic and molecular basis of a premature aging disorder.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by genomic instability and by the premature onset of a number of age-related diseases, including cancers. The gene responsible for WS encodes a protein that has an exonuclease domain and a domain similar to DNA helicases of the RecQ-like subfamily. Accumulating evidence indicates that the WS gene product is involved in resolving aberrant DNA structures that may arise during the process of DNA replication and transcription.

Captopril suppression versus salt loading in confirming primary aldosteronism.

This prospective study was designed to compare the captopril suppression test with the salt-loading approach to confirm the diagnosis of primary aldosteronism. A total of 49 patients were referred with a presumed diagnosis of primary aldosteronism. The captopril test was performed in the morning with patients in the seated position after overnight fasting.

The 2000 Canadian recommendations for the management of hypertension: Part one--therapy.

Objective: To provide updated, evidence-based recommendations for the therapy of hypertension in adults.

Options: For patients with hypertension, there are a number of lifestyle manoeuvres and antihypertensive agents that may control blood pressure. Randomized trials evaluating first- line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed.

Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme of dopamine and (nor)adrenaline biosynthesis. Regulation of its gene expression is complex and different regulatory mechanisms appear to be operative in various neuronal lineages. Pitx3, a homeodomain-containing transcription factor, has been cloned from neuronal tissues and, in the CNS, mouse Pitx3 is exclusively expressed in midbrain dopaminergic (MesDA) neurons from embryonic day 11 (E11).

Tumorigenic effect of nonfunctional p53 or p21 in mice mutant in the Werner syndrome helicase.

Werner syndrome is an autosomal recessive disorder characterized by genomic instability and by the premature onset of a number of age-related diseases, including malignancy. To assess a potential collaboration between p21 or p53 cell cycle regulators and Wrn proteins, Wrn mutant mice were created and mated with p21 or p53 null mice to generate double mutants. The p21 null/Wrn mutant mice did not show an acceleration of tumorigenesis during the first year of life, suggesting that the p53-dependent G1-S cell cycle checkpoint (which operates via p21) is not involved in Wrn-abetted tumor suppression.

Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats.

Background: We documented recently that increased endothelin-1 (ET-1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET-1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure.

Chronic nitric oxide inhibition aggravates hypertension in erythropoietin-treated renal failure rats.

Alterations in nitric oxide (NO) and endothelin-1 (ET-1) production have recently been reported in erythropoietin (r-HuEPO)-induced hypertension in renal failure rats. The present study was designed to evaluate the effect of NO synthase inhibition with the L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) on blood pressure (BP) and ET-1 production in control and in uremic rats treated or not treated with r-HuEPO. Renal failure was induced by a two-stage 5/6 nephrectomy.

The Immunization Monitoring Program Active (IMPACT) prospective five year study of Canadian children hospitalized for chickenpox or an associated complication.

Background: Varicella vaccine was approved for use in Canada in 1998. A major goal of universal varicella vaccine programs is to reduce severe infection and associated complications. Baseline data are essential against which to judge the effectiveness of routine childhood immunization.

Who needs individual bioequivalence studies for narrow therapeutic index drugs? A case for warfarin.

Warfarin is, among drugs, considered to have a narrow therapeutic index for which individual bioequivalence has been suggested. To establish the propriety of "switching," an individual bioequivalence study involving a replicate-design study and three "switchings" in healthy subjects was undertaken using the U.S.

Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the hemolytic-uremic syndrome.

Background: Fewer than 10% of children with Escherichia coli O157:H7 enteritis develop hemolytic-uremic syndrome (HUS).

Objective: To determine whether circulating leukocytes are independent risk markers of developing HUS during E. coli O157:H7 enteritis.

Specific protein-protein interaction between basic helix-loop-helix transcription factors and homeoproteins of the Pitx family.

Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1.

The Werner syndrome gene product co-purifies with the DNA replication complex and interacts with PCNA and topoisomerase I.

Werner syndrome (WS) is a recessive disorder characterized by genomic instability and by the premature onset of a number of age-related diseases. To understand the molecular basis of this disease, we deleted a segment of the murine Wrn gene and created Wrn-deficient embryonic stem (ES) cells. At the molecular level, wild type-but not mutant-WS protein co-purifies through a series of centrifugation, chromatography, and sucrose gradient steps with the well characterized 17 S multiprotein DNA replication complex.