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1 The pharmacokinetic parameters of morphine were determined in a crossover fashion following 4 days pretreatment with cimetidine, 300 mg every 6 h, or placebo. 2 Cimetidine had no apparent effect on the mean morphine plasma clearance, volume of distribution, AUC or half-life (P greater than 0.05; power greater than 0.80). 3 Cimetidine had no apparent effect on the magnitude or duration of morphine induced miosis. 4 The absence of a demonstrable effect on the pharmacokinetics of a drug with a high extraction ratio such as morphine suggests that cimetidine did not significantly reduce hepatic blood flow in ambulant normal volunteers. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations., Design: Case control study over three years., Setting: An 800 bed general municipal hospital., Subjects: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography., Interventions: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate., Main Outcome Measure: Postprandial lipoprotein metabolism., Results: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82)., Conclusion: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.

The penetration of ciprofloxacin into the ascitic fluid of eight patients was studied. Serum and ascitic fluid samples were obtained before and at 1, 2, 3, 6, and 12 h following administration of a single oral dose of 750 mg. Peak levels (mean +/- standard deviation) were 4.0 +/- 0.7 micrograms/ml in serum and 2.6 +/- 0.6 micrograms/ml in ascitic fluid; the areas under the curve (0 to 12 h) were 29.1 +/- 6.5 micrograms.h/ml in serum and 20.7 +/- 5.0 micrograms.h/ml in ascitic fluid. The concentrations that were achieved are well above the MICs of ciprofloxacin for the members of the family Enterobacteriaceae that cause spontaneous bacterial peritonitis.

The epidemiologic, clinical, and laboratory aspects of group A streptococcal bacteremia were studied in 33 patients seen at two urban hospitals in the Tel Aviv (Israel) area, over an 8-year period. Most patients (two-thirds) were female. Clinically significant bacteremia was observed in 26 patients, two of whom acquired their infection (puerperal sepsis) during hospitalization. A portal of entry, mainly cutaneous, was recognized in 61% of the patients, and a chronic underlying condition was observed in 69%. The case-fatality rate was 27%, with death occurring predominantly in patients admitted with shock or cryptogenic bacteremia. Our clinical experience and literature review show that the presentation of group A streptococcal bacteremia is diverse, with transient bacteremia of uncertain clinical significance on one end of the spectrum and overwhelming sepsis on the other. A practical classification of the various clinical forms of group A streptococcal bacteremia is proposed.

Forty-two patients with a history of symptomatic ventricular tachycardia or cardiac arrest underwent electrophysiologic testing at control and early in the course of amiodarone therapy (mean 12 +/- 7 days). Late electrophysiologic studies (mean 17 +/- 4 weeks) were repeated in 23 patients on a maintenance dose of 400 mg/day. At control study, all patients had inducible ventricular tachyarrhythmias (sustained ventricular tachycardia in 35, nonsustained ventricular tachycardia in 4, ventricular fibrillation in 3), while after amiodarone loading (1,200 mg daily) 4 (10.5%) of the 42 patients developed noninducible ventricular arrhythmias. At late study, an additional 6 (26%) of the 23 patients with inducible arrhythmias at early study developed noninducible arrhythmias. The cycle length of induced ventricular tachycardia increased from 275 +/- 61 ms at control study to 340 +/- 58 ms at early study (p = 0.001). A further increase in ventricular tachycardia cycle length was noted in patients who underwent both early and late study (341 +/- 38 versus 375 +/- 63 ms, p less than 0.05). The percent of induced tachycardias that were clinically tolerated increased as patients were treated longer with amiodarone (control = 22%, early = 34%, late = 53%, p less than 0.001). Of the 23 patients who had both early and late electrophysiologic studies and were followed up for a mean of 21.7 months (range 4 to 47), there were no recurrences among the 6 patients with noninducible arrhythmias, but there were five recurrences among the 17 patients with persistently inducible arrhythmias. None of the four patients with noninducible arrhythmias at early study had a recurrence. On the basis of these findings, it is concluded that: 1) The timing of programmed electrical stimulation will affect the results of the study in patients treated with oral amiodarone.(ABSTRACT TRUNCATED AT 250 WORDS)

To compare the antihypertensive and humoral effects of the angiotensin-converting enzyme inhibitors captopril and enalapril, 20 patients with essential hypertension, not receiving treatment for 2 weeks and consuming a prescribed sodium ion intake, were randomly assigned to two parallel, double-blind treatment groups with stratification based on race and untreated seated diastolic blood pressure. These groups received a placebo (day -1) followed by either captopril, 200 mg every 12 hours (n = 9), or enalapril maleate, 20 mg every 12 hours (n = 11), alone (days 1 to 14) and then with hydrochlorothiazide, 25 mg every 12 hours (days 16 to 28). Captopril and enalapril were coadministered alone (day 15) and with hydrochlorothiazide (day 29) to assess whether further decreases in blood pressure would occur. Captopril and enalapril alone caused comparable decreases (p less than 0.05) in the mean 12 hour time-averaged seated diastolic blood pressure from values on day -1 (placebo), on day 1 (11 and 9 mm Hg, respectively) and day 14 (8 and 7 mm Hg, respectively). The addition of hydrochlorothiazide further decreased (p less than 0.05) blood pressure in each group (7 and 8 mm Hg, respectively) from values on day 14. Combined use of captopril and enalapril did not result in further reduction. Coupled with the comparable changes observed in each treatment group in serum angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration, these data support the view that captopril and enalapril have similar antihypertensive effects and mechanisms.

Single doses of norfloxacin (200, 400, 800, 1,200, and 1,600 mg) or placebo were administered orally at weekly intervals to 14 healthy male volunteers in a double-blind study. Norfloxacin was measured in serum and urine by high-pressure liquid chromatography with UV detection. The concentrations of this drug in serum peaked 1 to 2 h after each dose; the mean peak values for increasing doses were 0.75, 1.58, 2.41, 3.15, and 3.87 micrograms/ml. Mean area under the serum concentration-time curves for the first 12 h after each dose were 3.56, 6.26, 11.4, 16.1, and 19.7 micrograms . h/ml, respectively. The elimination half-life of norfloxacin was about 7 h and was similar for all doses. The concentrations of the drug in urine also peaked 1 to 2 h after dosage; mean peak values for increasing doses were 200, 478, 697, 992, and 1,045 micrograms/ml. Renal clearances approximated 285 ml/min. About 30% of each dose was excreted into urine as unmetabolized norfloxacin. Crystals of the drug were occasionally observed during microscopic examination of freshly voided urine collected after the 1,200- and 1,600-mg doses. Crystalluria was not encountered at lower doses.

The serum concentrations and beta-blockade after dermal application of timolol ointment were evaluated in six healthy men (21-31 years old; 74-82 kg). Two patches (25 cm2) containing placebo and either 30 (n = 2) or 60 mg (n = 4) timolol base were randomly applied to the chest for 30 h. Serial serum concentrations of timolol were measured by a radioligand receptor assay. Bicycle ergometry, at a predetermined workload, was performed before and at 3, 8, 24, and 48 h after patch application; mean +/- SD heart rates (beats/min) at these times were 167 +/- 2, 158 +/- 7, 125 +/- 7, 120 +/- 5, and 150 +/- 5 (last 3 values: p less than 0.05 from pretreatment), and beta-blockade was evident in all subjects. Measurable serum concentrations in the therapeutic range were achieved in all subjects. The change in exercise-induced heart rate (y) was closely related to log timolol serum concentration (x) (y = -36 X - 5.3; r = -0.92; p less than 0.001). Based on the amount of timolol in the residual ointment, 50-60% of the original timolol dosage was delivered from the patch. Skin irritation under the patch compared with placebo was minimal. Further studies are warranted to assess the potential clinical utility of transdermal timolol.

A 28-year-old man is described with no demonstrable organic heart disease and recurrent paroxysmal attacks of sustained ventricular tachycardia. Lignocaine and ajmaline failed to terminate the first attack but a bolus infection of verapamil succeeded. This drug was subsequently successful on six more occasions. During electrophysiological study of the eighth attack, slow intravenous administration of verapamil significantly reduced the rate of the tachycardia and prevented its subsequent reinitiation by pacing. Two mechanisms are postulated to explain both the arrhythmia and the beneficial effects of verapamil in this case.

Cholestatic jaundice associated with chills, pruritus and blood eosinophilia developed in a patient who received prajmalium bitartrate therapy for ventricular arrhythmia following acute myocardial infarction. Discontinuation of the drug resulted in a spontaneous improvement in the clinical and biochemical findings. Challenge by prajmalium bitartrate caused rapid reappearance of the clinical and biochemical features. In immunological studies, deposits of IgG and IgA were detected at the bile canaliculi by fluorescent staining, and the patient's lymphocytes produced macrophage migration inhibition after in vitro incubation with prajmalium bitartrate. Thus, laboratory results support the assumption of an allergic mechanism.

Chlamydia trachomatis was isolated from perianal lesions in a patient in whom lymphogranuloma venereum had been diagnosed 20 years previously. Treatment with tetracycline resulted in a pronounced improvement. Although C trachomatis is known to persist for a long time in the host, isolation of the micro-organism from infected tissues after such a prolonged period has not previously been reported.