Fixed combination of losartan and hydrochlorothiazide and reduction of risk of stroke

A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin-angiotensin-aldosterone-system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.     

Cloning of glycoprotein IIIa cDNA from human erythroleukemia cells and localization of the gene to chromosome 17

Platelet aggregation requires the binding of adhesive proteins such as fibrinogen to the heterodimer of membrane glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Human erythroleukemia (HEL) cells synthesize both GPIIb and GPIIIa. Using poly(A+) RNA purified from HEL cells, we constructed a cDNA library in the lambda gt10 phage vector. This library was screened with a 38mer oligonucleotide derived from a platelet GPIIIa peptide, and three overlapping cDNAs were isolated. The three inserts encompassed 3.5 kilobases (kb), including the entire coding region of mature GPIIIa (2,286 basepairs, bp) and 1.3 kb of 3' untranslated sequence. All 222 residues determined directly from platelet GPIIIa tryptic peptides exactly matched the HEL cell-deduced amino acid sequence. The HEL cell sequence matched a previously reported endothelial cell cDNA sequence except for eight nucleotides. Five of these nucleotide differences were silent changes consistent with genetic polymorphisms. The other three differences resulted in changes in the deduced amino acid sequence of GPIIIa; reexamination of the endothelial cell cDNA sequence in these three areas revealed that it is actually identical to the HEL cell sequence. The virtual identity of the endothelial and HEL cell cDNA sequences provides direct evidence that GPIIIa is a subunit common to cell-adhesion receptors present in more than one cell type. We localized the gene for GPIIIa to chromosome 17, the same chromosome to which we had previously mapped the gene for GPIIb.     

The effects of losartan compared to atenolol on stroke in patients with isolated systolic hypertension and left ventricular hypertrophy. The LIFE study

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study reported that a losartan-based antihypertensive regimen reduced cardiovascular morbidity and mortality (composite of cardiovascular death, stroke, and myocardial infarction) more than therapy based on atenolol in patients with left ventricular hypertrophy and isolated systolic hypertension (ISH). Patients aged 55-80 years with blood pressures 160-200/<90 mm Hg were followed for a mean of 4.7 years. Blood pressure was similarly reduced in the losartan (n=660) and atenolol (n=666) ISH groups. There were 88 (6.6%) patients who experienced a stroke, 18 of which were fatal. Of patients experiencing strokes, 72.7% had an ischemic stroke. ISH patients in LIFE compared to the non-ISH group had a higher incidence of any stroke and embolic stroke, and similar incidences of fatal, atherosclerotic, and hemorrhagic/other strokes. The incidence of any stroke (40% risk reduction [RR], p=0.02), fatal stroke (70% RR, p=0.035), and atherothrombotic stroke (45% RR, p=0.022) was significantly lower in losartan-treated compared to the atenolol-treated patients. The 36% RR for embolic strokes in the losartan group was not statistically significantly (p=0.33) different from the atenolol group. These data suggest that losartan-based treatment is more effective than an atenolol-based treatment for patients with ISH and a high risk for stroke.     

Purification and characterization of a peptidyl glycine monooxygenase from porcine pituitary

A peptide alpha-amidating enzyme was purified to apparent homogeneity from porcine pituitary. This enzyme is a glycoprotein with a mol wt of 64,000, a metal prosthetic group, and a dependence upon ascorbate and molecular oxygen. The purified enzyme has a strong preference for peptides ending in glycine. It also catalyzes the oxidation of valylglycine bonds more rapidly than prolylglycine bonds, and demonstrates a primary isotope effect greater than 5 when the alpha-hydrogens of glycine are replaced by deuterium. Kinetic analysis is consistent with a ping-pong or double displacement catalytic mechanism in which both the peptide substrate and ascorbate are competitive inhibitors with respect to each other. With respect to its kinetic properties, catalytic mechanism, and cofactor requirements, the purified amidating enzyme is very similar to dopamine beta-hydroxylase, a finding which supports the previous suggestion that the peptide alpha-amidating enzyme be classified as a peptidyl glycine monooxygenase.     

Lipoid pneumonitis in a commercial abalone diver

This report describes the clinical and pulmonary function manifestations found in a 37-yr-old commercial abalone diver who developed diffuse lipoid pneumonitis due to inhalation of aerosolized mineral oil contained in the unfiltered air generated from his surface air compressor. Four years later, the patient continued to be symptomatic with shortness of breath and dyspnea during exertion, and repeat physiologic evaluation continued to demonstrate findings of a restrictive ventilatory defect.     

卵圆孔未闭与年轻人不明原因脑卒中

1例38岁男性描述在阅读时突然出现右侧视野偏盲。该患者无重要病史，且自诉无吸烟、饮酒和服用违禁药物的情况。体格检查显示，除右侧同侧偏盲外无其他异常。MRI显示急性左枕叶梗死，头部和颈部血管正常。经食管超声心动图显示为卵圆孔未闭，无房间隔瘤。     

Alcohol-related mortality in California, 1980 to 1989.

OBJECTIVES. This study sought to examine the impact of alcohol use and misuse on mortality in California during the 1980s. METHODS. Alcohol-Related Disease Impact estimation software and California vital statistics data were used to calculate alcohol-related mortality, mortality rates, and years of potential life lost. Statistical tests were applied to detect significant differences in death rates by sex and race/ethnicity. Time trends in death rates for a subset of alcohol-defined diagnoses were examined using regression analysis. RESULTS. An estimated 6.2% of all deaths for California residents during 1989 were related to alcohol, making it one of the top 10 leading causes of death. Injury diagnoses were major contributors to the total estimated number of alcohol-related deaths and years of potential life lost before age 65. Alcohol-related mortality rates were significantly higher for men and for Blacks. However, age-adjusted death rates for alcohol-defined diagnoses declined significantly from 1980 to 1989. CONCLUSIONS. A structured data-base approach to analyzing mortality data represents an important advance for alcohol research that has implications for policy and program planning. Future refinements and enhancements to the disease impact estimation methodology will add precision to determining how alcohol use and misuse affect public health in California.