Single course versus maintenance bacillus Calmette-Guerin therapy for superficial bladder tumors: a prospective, randomized trial

A total of 42 patients with recurrent superficial bladder tumors or carcinoma in situ entered a prospective, randomized trial to compare the efficacy of bacillus Calmette-Guerin therapy with and without quarterly maintenance instillations of bacillus Calmette-Guerin. Maintenance therapy did not reduce further bladder tumor recurrence rates or the interval to recurrence in patients who responded to the initial course of therapy. However, prolongation of toxicity was observed with maintenance bacillus Calmette-Guerin therapy.     

An antinociceptive profile of kojic amine: an analogue of gamma-aminobutyric acid (GABA)

Kojic amine [2-(aminomethyl)-5-hydroxy-4H-pyran-4-one], an analogue of gamma-aminobutyric acid (GABA), produced dose-related, but short-lived, antinociceptive activity in the 48 degrees C [ED50 = 9.2 (8.2-10.3) mg/kg i.p.] and 55 degrees C [ED50 = 13.8 (12.2-15.7) mg/kg i.p.] hot-plate tests in the mouse. The antinociceptive activity of kojic amine at 48 degrees C was found to be insensitive to bicuculline (1.0 mg/kg i.p.) and picrotoxin (0.5 mg/kg i.p.). At this temperature, antinociception was distinctly separate from the impairment of motor function (measured by a rotorod assay) and was not significantly affected by prior treatment with the cholinergic antagonist, atropine sulfate (10.0 mg/kg i.p.). However, at 55 degrees C, the antinociceptive effect of a large dose (20 mg/kg i.p.) of kojic amine was significantly attenuated by similar pretreatment with atropine sulfate, but not by the peripheral cholinergic antagonist, atropine methylnitrate (10.0 mg/kg i.p.). Kojic amine exhibited no significant interaction with haloperidol (0.5 mg/kg i.p.) at this temperature. In animals made tolerant to morphine, THIP or baclofen, there was analgesic cross-tolerance between kojic amine, morphine and baclofen but not between kojic amine and THIP. It is suggested that kojic amine-induced antinociception is similar to that produced by both THIP and baclofen. Thus, kojic amine represents a unique tool with which to study GABA-ergic antinociceptive processes.     

Computed tomography of the brain in the Smith-Lemli-Opitz syndrome

Computed tomographic (CT) scans of the brain in a child with Smith-Lemli-Opitz syndrome revealed enlargement of the ventricular system, hypoplasia of the cerebellum, and abnormal thickening of the gray matter, consistent with pachygyria. These findings have been previously noted in autopsies performed on patients with this disorder. We conclude that CT scanning is a valuable tool in the evaluation of children suspected of having the Smith-Lemli-Opitz syndrome.     

Fate of the monoamine oxidase inhibitor pargyline in cultured hepatocytes

The interaction of the monoamine oxidase inhibitor pargyline with cultured hepatocytes has been studied. [Phenyl-3, benzyl-3H] pargyline (38 nM) rapidly enters the cells and a plateau of incorporation into a trichloroacetic acid insoluble form (monoamine oxidase) is reached after 2 hr. The level of labelling is lower in freshly isolated cells than in those in later culture. The maximum incorporation accounts for only 6% of the added radioactivity and produces a 9% inhibition of monoamine oxidase activity. The remaining [3H] pargyline is metabolized and quickly accumulates in the cell culture medium in a form which cannot label exogenous mitochondria. The metabolism of pargyline varies both qualitatively and quantitatively with culture age. In 0 hr and 20 hr-cultured cells one metabolite preferentially appears whilst in 140 hr cultured hepatocytes at least three metabolites are formed. The metabolism of [3H] pargyline in early culture is consistent with a cytochrome P-450 involvement. The use of [3H] pargyline to label monoamine oxidase in cultured hepatocytes offers several attractive features for studying the turnover of this enzyme. These include speed of interaction, non-reutilization, application to normal cells, controlled inhibition of monoamine oxidase and metabolism of non-specific label.     

Long-lasting effects of chronic chlorimipramine treatment of rats on exploratory activity on a hole-board, and on immobility in the forced swimming test

The study concerned the effects of acute and chronic clomipramine administration to male rats on exploratory activity in a novel environment (hole-board) and on immobility in the forced swimming test. Acute clomipramine administration did not alter either exploratory activity on a hole-board as measured 3 or 20 h after drug administration, or immobility in the forced swimming test as measured 20 h after drug administration. Approximately 20 h after the last injection of clomipramine, the rats chronically treated with the drug showed reduced exploratory activity on the hole-board. In contrast, chronic clomipramine treatment significantly increased the activity in the forced swimming test. The effects of the drug on exploratory and forced swimming activities persisted for 14 days after the cessation of clomipramine administration. These data indicate that chronic clomipramine administration exerted profound and long-lasting effects on central nervous system function. The long-lasting action of the drug on behaviour in the forced swimming test might explain the long-term beneficial effect of antidepressant drugs in counteracting behavioral depression.     

Biomechanical comparison of stimulated and nonstimulated skeletal muscle pulled to failure

We compared the biomechanical properties of passive and stimulated muscle rapidly lengthened to failure in an experimental animal model. The mechanical parameters compared were force to tear, change in length to tear, site of failure, and energy absorbed by the muscle-tendon unit before failure. Paired comparisons were made between 1) muscles stimulated at 64 Hz (tetanic stimulation) and passive (no stimulation) muscles, 2) muscles stimulated at 16 Hz (wave-summated stimulation) and passive muscles, and 3) muscles stimulated at 64 Hz and at 16 Hz. Both tetanically stimulated and wave-summation contracted muscles required a greater force to tear (at 64 Hz, 12.86 N more, P less than 0.0004; and at 16 Hz, 17.79 N more, P less than 0.003) than their nonstimulated controls, while there was no statistical difference in failure force between muscles stimulated at 16 Hz and 64 Hz. The energy absorbed was statistically greater for the stimulated muscles than for the passive muscles in Groups 1 and 2 (at 64 Hz, 100% more, P less than 0.0003; and 16 Hz, 88% more, P less than 0.0002). In Group 3, the tetanically contracted muscle-tendon units absorbed 18% more energy than the wave-summated stimulated muscles (P less than 0.01). All muscles tore at the distal musculotendinous junction, and there was no difference in the length increase at tear between muscles in each group. These findings may lead to enhanced understanding of the mechanism and physiology of muscle strain injuries.     

Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.