Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure

BACKGROUND: The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. METHODS AND RESULTS: Thirty-six men (mean age+/-SD, 55+/-8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4+/-4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], -13.9% [-16.0% to -11.7%]), pulmonary artery mean (-12.9% [-17. 4% to -8.3%]) and capillary wedge (-14.5% [-20.5% to -8.5%]) pressures, and right atrial pressure (-20.2% [-29.4% to -11.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (-24.2% [-28.1% to -20.3%]) and pulmonary (-19.9% [-28.4% to -11.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15. 2% [10.8% to 19.6%]) and systemic (-9.3% [-12.3% to -6.4%]) and pulmonary (-9.7% [-16.3% to -3.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged. CONCLUSIONS: Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.     

Effect of temperature on the Electrochemical corrosion behaviour of titanium

The influence of variations in temperature on the electrochemical corrosion properties of VT 1-0 commercial titanium was studied in deaerated 1 mol/dm³ sulphuric acid between 293 and 353 K. Galvanostatic and quasi-potentiostatic polarization measurements were carried out. Corrosion rates were determined by mass loss measurements, too. The slopes of the cathodic Tafel-like lines obtained with galvanostatic polarization change anomalously with temperature. The corrosion rates calculated from the mass loss data increase with increasing temperature at a higher rate than those determined with the polarization method, pointing to a self-dissolution process. The results are attributed to a hydride layer with a H/Ti ratio increasing with temperature. Titanium hydride may play a dominant role both in the hydrogen evolution reaction and in the self-dissolution process.     

A study of "atypical schizophrenia". Comparison with schizophrenia and affective disorder by sex, age of admission, precipitant, outcome, and family history

Eighty-five cases of atypical schizophrenia were compared with 200 of schizophrenia, 100 of bipolar (mania), and 225 of unipolar (depression) affective disorder. Comparisons were made on the basis of sex, age at admission, precipitating factors, outcome, and a family history of schizophrenia or of affective disorder. The atypical schizophrenia differed remarkably from the schizophrenia and most closely resembled the bipolar affective disorder when allowance was made for a younger age at onset and a higher frequency of precipitants. An analysis of symptoms verified the predominance of schizophrenic features in the atypical schizophrenia, but also showed a high percentage (80%) of patients who had one or more manic symptoms at index admission. It is concluded that great care should be taken in diagnosing schizophrenia in a patient who also has manic symptoms.     

Isolation, crystallization and preliminary crystallographic data of aspartate aminotransferase from chicken heart mitochondria

A series of 238 hydronephrotic kidneys in 219 children is reported. The condition was more common in the male than in the female subject and occurred more frequently on the left side. It was often bilateral, especially in infants, with an abdominal mass as the common presenting feature. Loin or abdominal pain was the most frequent complaint in older children. In some cases hydronephrosis presented as a ruptured kidney following trauma. Only 1 patient was hypertensive. The lesion was asymptomatic in 18 cases and the incidence of urinary infection was low. Dismembered pyeloureteroplasty was the procedure of choice for reconstruction. Preliminary nephrostomy was used rarely and nephrectomy was done in 10 per cent of the kidneys. Of the 7 reoperations 4 were for persistent obstruction and 3 were because stones had formed after the pyeloplasty. The late results, assessed clinically and radiologically, have been entirely satisfactory. Many kidneys of initially doubtful value showed useful improvement after reconstructive operation and no secondary nephrectomies were performed. The only death in the series occurred 2 1/2 years postoperatively and was unrelated to the urinary tract.     

Validated capillary electrophoresis method for the determination of atropine and scopolamine derivatives in pharmaceutical formulations

The simultaneous determination of atropine and scopolamine derivatives, which have similar structures, was investigated by using capillary zone electrophoresis. The effects of buffer pH, buffer concentration and hydroxypropyl-beta-cyclodextrin concentration on migration time and resolution of the investigated compounds were systematically studied. The selected electrophoretic buffer consisted of a 80 mM sodium citrate pH 2.5, containing 2.5 mM hydroxypropyl-beta-cyclodextrin as the complexing agent. Quantitative analysis was validated by testing the reproducibility of the method, giving a relative standard deviation less than 1 and 2% for the intermediate precision of migration times and peak area ratios, respectively. The linearity of the method was assessed between 50 and 150% of the theoretical content (coefficient of correlation greater than 0.99). The proposed method was found to be suitable and accurate for the determination of these basic drugs in pharmaceutical preparations.