No abstract

The anxiolytic activity of methylclonazepam was compared to lorazepam and placebo in a double-blind, randomized cross-over study, using a latin square design, in 18 inpatients meeting Research Diagnostic Criteria for Generalized Anxiety Disorders. Patients presented at least 1 year of symptomatology and had a minimum score of 20 on the Hamilton Anxiety Scale, despite chronic anxiolytic pharmacotherapy. Daily dosage was flexible, from three to six tablets of methylclonazepam 1 mg, lorazepam 2.5 mg, or placebo. Clinical evaluation included Hamilton Anxiety Scale, Clinical Global Impression (CGI), a side-effects checklist, completed every 2 days, and the global preference of the patient for one of the treatment periods. Results showed a highly significant superiority of both benzodiazepines over placebo on the Hamilton Scale (P less than 0.000001) and CGI (P less than 0.001), and also a significant superiority of methylclonazepam over lorazepam on the Hamilton Scale (P less than 0.01), CGI-1 (P less than 0.01), and in the number of patient preferences (14 versus 1; P less than 0.001), with no significant differences in side-effects or related to position in the trial. These results support the value of the cross-over design in chronic and severe anxious inpatients for the demonstration of differences in efficacy between anxiolytic pharmacotherapies.

No abstract

The early changes in tubular reabsorption, glomerular filtration, blood flow and sodium excretion brought about by uranyl nitrate were investigated in isolated, blood-perfused dog kidneys during water diuresis. No significant changes in urine volume were observed; the decrease in fluid reabsorption was counterbalanced quantitatively by a reduction in glomerular filtration rate; only a small diminution of renal blood flow was found. The balance between reabsorption and filtration was observed as well when angiotensin action or prostaglandin synthesis were inhibited. The intrarenal venous pressure rose, suggesting that an increase in proximal intratubular hydrostatic pressure caused the decrease in filtration. Tubular back-leak of fluid, or back-diffusion, induced by the toxin, were excluded. The presence of natriuretic compounds in the urine was confirmed.

Tubular reabsorption was inhibited in isolated dog kidneys by the progressive substitution of plasma chloride by sulphate. In the absence of antidiuretic hormone activity, urine output remained unchanged owing to an equivalent decrease in glomerular filtration rate. This equilibrium was demonstrated under conditions of "saline natriuresis" and was not disturbed by furosemide. Although the impairment of glomerular filtration rate was accompanied by a decrease of total renal blood flow, the equilibrium was not disrupted by angiotensin antagonism. Sodium excretion was enhanced by low plasma chloride concentrations in the absence, but not in the presence of furosemide. The results are not compatible with a specific role of osmolality, sodium or chloride concentrations in the tubular fluid in the adjustment of glomerular filtration. Simultaneous changes in blood flow and tubular flow resistances might explain the results. It is suggested that, in contrast to the mechanism of tubulo-glomerular feedback found in individual nephrons of hydropenic animals, this intrarenal mechanism might serve to protect the organism against sodium loss under conditions of high intake.