Changes in bile saturation and biliary bile acid composition in patients with gallstones who received chenodeoxycholic ("chenic") acid, cholic acid, or placebo were measured. Chenodeoxycholic induced bile desaturation; this effect was attributable solely to a decrease in the proportion of cholesterol. By gas chromatography, chenodeoxycholic acid increased substantially in the biliary bile acids of patients receiving it, and by mass spectrometry, no unusual bile acids were detected in appreciable amounts. Changes in bile saturation and biliary bile acid composition were then related to chenodeoxycholic acid dosage, and all of these variables were, in turn, related to gallstone response. In general, patients whose gallstones dissolved ingested a higher dose of chenodeoxycholic acid or had bile that contained a higher proportion of this acid and it was more unsaturated, but there were many exceptions, casting doubt on the value of a single analysis of fasting-state bile for predicting gallstone dissolutions. The major factor influencing response, provided dosage is adequate, appears to be gallstone type. Nonetheless, the proportion of chenodeoxycholic acid in biliary bile acids can probably be used to infer patient compliance.

Clinical experience with chenodeoxycholic acid therapy for dissolving gallstones is reported, with particular attention to determinants of response. Of 12 patients receiving 15 mg/kg/day or more, ten responded (83%); only 15 of 40 patients (38%) receiving less than 15 mg/kg/day responded. Large solitary stones and stones in gallbladders that visualized poorly after oral cholecystography had a lower response rate. Radiopaque stones did not respond in 18 patients. Five of ten patients with stones in the common bile duct responded. Small, dose-related elevations in SGOT were the only biochemical abnormality observed. Liver biopsy specimens showed no notable abnormality. Diarrhea was an infrequent problem. Stones recurred in three of 15 patients during six to 48 months of observation without treatment. Chenodeoxycholic acid, when given in adequate dosage, continues to appear promising as medical therapy for asymptomatic radiolucent gallstones in radiologically visualizing gallbladders.

Clinical studies of 6- and 12-valent pneumococcal capsular polysaccharide vaccines were carried out in controlled studies among novice gold miners in South Africa. In the studies 1,523 persons received pneumococcal vaccine, and 3,171 were included as controls. In the great majority of subjects given pneumococcal vaccine, antibodies developed against the capsular types included in the vaccine. The 6-valent vaccine afforded 76% reduction in cases of laboratory-verified pneumococcal pneumonia caused by the homologous types, and there was 92% reduction in the cases afforded by the 12-valent vaccine. The vaccines were well tolerated and offer great promise for effective control of illnesses caused by pneumococci.

The chemical structure of probucol differs from that of other hypolipemic agents, and its mechanism of action is unknown. This agent lowers elevated serum cholesterol (and low-density lipoprotein) levels and appears to be effective when used as an adjunct to a low-cholesterol, low-saturated-fat diet for treatment of type IIa hyperlipoproteinimia in adults; however, it is less effective than cholestyramine resin in patients with familial type IIa disorder. Although probucol has no consistent effect on elevated triglyceride levels, it may be useful as an adjunct to other drugs that lower these concentrations in patients with types IIb, III, and IV hyperlipoproteinemia when hypercholesterolemia persists. Probucol is generally well tolerated.

Lergotrile mesylate, an ergot alkaloid derivative and putative dopamine agonist, was effective in the majority of patients with Parkinson's disease who were showing signs of disease progression despite treatment with levodopa combined with a peripheral decarboxylase inhibitor (carbidopa). Among 20 patients completing a six-month trial, there was a significant (P less than .01) reduction in rigidity, tremor, bradykinesia, gait disturbance, and total score when lergotrile was added to levodopa plus carbidopa. Mean daily dose of lergotrile mesylate was 52 mg, and the mean daily dose of levodopa was reduced by 15%. Abnormal involuntary movements were decreased on addition of lergotrile and reduction in levodopa while mental changes and orthostatic hypotension were increased. Elevations in serum transaminase levels were noted in three patients. The ergot alkaloids promise to be an important new class of antiparkinsonian drugs.

The bronchodilator effects of aerosols of a high-dose of terbutaline sulfate (1.5 mg), a low-dose of terbutaline sulfate (0.75 mg), isoproterenol (0.3 mg), and placebo were compared using forced expiratory spirometry, flow-volume curves, and body plethysmography in a double-blind, six-hour, controlled study in 25 patients with reversible airflow obstruction. After isoproterenol therapy, the values peaked at 15 minutes, and none were significantly different (P less than .05) from placebo after the 30-minute observation point. The values for high-dose terbutaline peaked at one hour at a level that exceeded responses to isoproterenol. All values except the forced vital capacity at five and six hours and functional residual capacity at six hours were significantly greater than placebo (P less than .05) at all observation points. The low-dose terbutaline values peaked earlier and at a lower value than the high-dose terbutaline values, and several indexes were significantly greater (P less than .05) than after isoproterenol therapy beyond the two-hour point.

Beclomethasone dipropionate was administered by aerosol to 30 patients whose chronic bronchial asthma required oral corticosteroid therapy. During the initial 12 weeks of the trial, beclomethasone therapy could be discontinued in 12 of 16 patients in contrast to only one of 14 patients receiving the inert aerosol placebo. Patients receiving the placebo were then given beclomethasone, and prednisone therapy was discontinued in five more. During six months of observation, adrenal function improved and steroid toxic reactions decreased in patients in whom oral corticosteroid therapy had been discontinued. Beclomethasone aerosol was generally well-tolerated. Asymptomatic thrush developed in four patients and rhinitis developed in ten patients as prednisone therapy was discontinued.

A randomized double-blind trial of 152 men with gonococcal urethritis compared the therapeutic efficacy of erythromycin estolate and erythromycin base. Twenty-one of 86 (24%) men treated with the estolate and 15 of 66 (23%) treated with the base had recurrent or persistent gonococcal infection when seen after a 9-g course of erythromycin. The serum erythromycin activity among estolate-treated patients (3.57 +/- 0.84 microgram/ml) was nearly twice that for base-treated patients (1.76 +/- 0.80 microgram/ml). Our findings do not support routine use of erythromycin for treatment of pregnant, penicillin-allergic patients.

A relative intolerance of lactose was demonstrated in 14 of 16 patients receiving nasogastric tube feedings following surgery for head or neck carcinoma. Two liquid diets differing only in the presence or absence of lactose, were administered for eight to 20 days per patient in a double-blind crossover study. Increased stool frequency, decreased stool consistency, and more frequent flatulence, borborygmi, and distention were found with the lactose diet, although classic lactose intolerance (plasma glucose rise of less than 26 mg/dl) was indicated in only two patients. Differences between amounts and times of peak rise following the glucose tolerance test and lactose tolerance test for each patient indicated the advisability of locating patients on a continuum of ability to hydrolyze lactose. The results indicate that lactose should be reduced or eliminated from tube-feeding diets to improve patient tolerance and comfort and to reduce diarrhea.

Seroconversion and adverse reaction rates were studied in 92 persons given four or five doses in a two-week period of duck embryo rabies vaccine (DEV) or duck embryo rabies vaccine purified by ultracentrifugation (P-DEV). Mouse-neutralizing antibodies developed in 78 of 92 (84.8%) persons in these accelerated schedules. There were no significant differences in the frequency of antibody conversion or in geometric mean titers of antibody between persons given either vaccine. However, local and systemic adverse reactions were substantially less common with P-DEV. These data suggest that four of five doses of DEV or P-DEV given in a two-week course can be used for preexposure prophylaxis in situations where the more drawn-out regimens would result in continuation of a high-risk of rabies exposure. The antibody response of persons given this more accelerated regimen must be determined.

Twenty-nine patients with small cell carcinoma of the lung and without evidence of brain metastasis were randomized into two treatment groups consisting of 14 patients who received prophylactic cranial irradiation (PCI) and 15 who received none (non-PCI). All patients were treated with irradiation of the primary lesion and concomitant chemotherapy. The response rate and median survival of the two groups were not significantly different: 93% and 7.2 months in the non-PCI; 86% and 9.8 months in the PCI; P larger than or equal to .05. Brain metastasis occurred in 0/14 patients in the PCI and 4/15 in the non-PCI (P less than or equal to .05) and was the cause of major neurologic disability in each. Although PCI did not improve response rate or survival, brain metastasis with its attendant neurologic complications was effectively prevented.

In a double-blind control study, oral doses of placebo, propoxyphene napsylate (50 or 100 mg), or codeine sulfate (30 or 60 mg) were administered to 46 postepisiotomy patients, grouped by severity of pain reported at first-dose drug administration. Eight hourly observations by a trained observer provided estimates of analgesia. The analgesia scores for placebo treatments were significantly lower than for the lesser doses of either drug (P less than .05) as well as for the greater doses (P less than .01). At both dose levels, the analgesia scores for both drugs were almost identical. Analgesia with the higher doses was greater than with the lower, but not to a statistically significant extent. The difference in patient responses increased following the second dose. No serious adverse reactions occurred; the elicited and volunteered reports of minor side effects were similar for all five treatments.

In a series of 450 patients with mild essential hypertension, propranolol alone (P), propranolol plus hydrochlorothiazide (P+T), propranolol plus hydralazine (P+H), and propranolol plus hydrochlorothiazide plus hydralazine (P+T+H) were compared to reserpine plus hydrochlorothiazide (R+T). Comparison was based on reduction of diastolic blood pressures (BP) to below 90 mm Hg and at least 5 mm Hg less than initial BP after six months of treatment. This was achieved in 92% of patients who received P+T+H, 88% taking R+T, 81% receiving P+T, 72% on P+H and 52% taking P alone. The number of drop-outs, morbid events, and terminating side effects were insignificantly different among the various regimens. In this study, P and P+H were less effective, while P+T and P+T+H were as effective as the standard regimen.

A total of 523 postmenopausal breast cancer patients with progressive disease were entered in a radomized, double-blind study of four dosages of diethylstibestrol (DES): 1.5, 15, 150, OR 1,500 MG/DAY. Higher dosages produced significantly (p less than .05) higher regression rates: 21% for the 1,500 mg dosage, 17% for the 150 mg dosage, 15% for the 15 mg dosage, and 10% for 1.5 mg dosage. Durations of regressions were similar regardless of the dosages used to induce them. Although the highest dosage produced the highest regression rate overall, selecting the best dosage or treatment of choice for each type of patient based on menopausal age and on dominant metastatic site would result in more regressions.