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.

In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.

The feasibility of determining the exact site and amount of drug-induced gastric bleeding was tested. Fourteen patients with rheumatoid arthritis received equivalent therapeutic doses of the antinflammatory drugs aspirin, 4 gm/day, and fenoprofen calcium, 2.4 gm/day, in randomized order for seven days. Acetaminophen was given for 14 days just prior to each of these periods. By fiberoptic gastroscopy, antral ulceration and acute mucosal lesions were found in seven patients following aspirin ingestion, in one taking fenoprofen, and in none taking acetaminophen. Fecal blood loss in four-day stool collections, quantitated by autologous chromium 51-labeled erythrocytes shed into the stool averaged 5.0 ml/day while taking aspirin, 2.2 ml/day while taking fenoprofen calcium, and 0.8 ml/day while taking acetaminophen. The mean blood loss was greater for those in whom gastric lesions developed while taking aspirin than for those in whom lesions did not develop. The short-term risk of erosive gastritis was greater for aspirin than fenoprofen.

Multiphasic screening as a case-finding tool was evaluated in a randomized, controlled study. For each of 112 physicians, a patient was assigned to one of three groups: multiphasic screening group (SG), chart abstract group (AG), or chart review group (RG). Medical problem lists constructed before and after receiving additional information were compared. Physicians for 36 SG patients identified considerably more new medical problems, both total (77) and ones they considered important (25), than 40 AG physicians (14 and 8) and 36 RG physicians (4 and 0). One year later, 38 of the 95 newly identified problems had been acted on, 31 in the SG. Medical care was affected in nine patients: six in SG, two in AG, and one in RG. Multiphasic screening may help physicians identify new medical problems in clinic patients.

A prospective randomized study comparing constant intravenous infusion of regular, low-dose insulin versus conventional subcutaneous administration of neutral protein Hagedorn (NPH) insulin in insulin-requiring patients undergoing orthopedic procedures under general anesthesia was undertaken. The degree of diabetic control was better in those receiving constant 2 units/hour of regular insulin than in those receiving two thirds of daily maintenance doses of NPH insulin. However, in two of eight patients receiving 2 units/hour, decreased insulin infusion rates and increased dextrose infusion rates were required to avoid hypoglycemia. Preoperative NPH insulin and 1 unit/hour insulin administration resulted in equivalent diabetic control.

In a double-blind study, 20 hypertensive patients were randomly assigned to a six-week regimen of either ticrynafen or hydrochlorothiazide. Blood pressure was significantly reduced with both medications, although most patients required an increase in dosage from 250 to 500 mg ticrynafen daily. Whereas the serum uric acid level rose moderately in the hydrochlorothiazide-treated patients, it fell strikingly to less than half of the pretreatment level in patients treated with ticryafen. Body weight decreased slightly in both groups, as did serum potassium levels. Blood urea nitrogen and serum creatinine levels rose slightly in both groups. The magnitude of these changes was not significantly different between the two groups. Use of ticryafen was well tolerated. Ticryafen appears to be a useful new antihypertensive agent because of its unique combination of diuretic, antihypertensive, and hypouricemic effects.

Three different dosages of vitamin C, dependent on body weight, were administered to 44 school-aged monozygotic twins for five months using a double-blind, co-twin control study design. The mothers recorded daily observations of cold symptoms, and multiple biochemical, anthropometric, and psychological measurements were made at the beginning and end of the study. Paired comparisons showed no significant overall treatment effect on cold symptoms, but the response was not uniform in all sub-groups. Treated girls in the youngest two groups had significantly shorter and less severe illness episodes, and an effect on severity was also observed in the youngest group of boys. The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study.

Heroin addicts were recruited for a 14-week open clinical comparison of methadone hydrochloride and methadyl acetate. Patients were randomly assigned to a methadyl acetate clinic in which methadyl acetate was dispensed to patients three times per week or to a methadone clinic in which methadone was dispensed six days per week. No statistically significant differences were observed between groups in retention rates, illicit drug use, employment rates, or arrest rates. The group treated with methadyl acetate had more dropouts in the first seven weeks than the second seven weeks: this pattern was reversed for the methadone-treated group. The differences were significant (P = .01). Spontaneously reported symptoms suggest that induction with methadyl acetate may be a more clinically variable phenomenon than induction with methadone. The reduction of number of clinic visits in the group treated with methadyl acetate was not a source of variance in treatment effectiveness.

Two hundred two patients participated in a double-blind random cross-over study of the effectiveness of human chorionic gonadotropin (HCG) vs placebo in a wieght reduction program. Serial measurements were made of weight, skin-fold thickness, dropout rates, reasons for dropping out, and patient subjective response. There was no statistically significant difference between those receiving HCG vs placebo during any phase of this study (P greater than .1).

Sixty-three patients with gonococcal arthritis completed a double-blind randomized penicillin therapy trial comparing a low dose regimen (procaine penicillin G, 600,000 units intramuscularly, given every 12 hours for up to ten days) with a high dose (the same procaine penicillin regimen and intravenous aqueous penicillin G, 10 million units daily, for the first three days). Pretherapy features were similar in the 36 patients allocated to low-dose vs the 27 to high-dose therapy. All patients had definite improvement within 48 hours of the initiation of either regimen. No therapeutic response variable studied differed significantly between the groups. Thus, no additional therapeutic benefit accrued from the high doses of penicillin. The absence of complications or failures in either treatment group indicate that gonococcal arthritis is ordinarily quite responsive to low doses of penicillin given intramuscularly, and that massive intravenous therapy is unnecessary.

Forty-one patients with clinical indications for heparin therapy were randomized to receive continuous intravenous heparin sodium therapy or intermittent (four-hourly bolus) heparin therapy, with control by the activated partial thromboplastin time. Seven of 21 patients receiving intermittent therapy had major bleeding episodes, whereas none of the 20 patients receiving continuous heparin therapy had major bleeding (P = .005). One patient on continuous therapy had a pulmonary embolus, while none on intermittent therapy had recurrent thromboembolism. Two heavily bleeding patients on intermittent therapy were switched to continuous treatment after bleeding was controlled. The use of continuous heparin therapy appears significantly safer with regard to hemorrhagic complications than the use of intermittent therapy.

The action mechanism of cromolyn sodium and its effect on bronchial sensitivity to allergen, methacholine chloride, and histamine inhalations were studied in 17 asthmatic subjects. Cromolyn capsules or placebo was administered by an inhaler (Spinhaler) randomly on alternate days 30 minutes before aerosol challenge. Cromolyn and placebo did not differ in their effect on bronchial response to histamine or methacholine. However, the degree of decrease in forced vital capacity and forced expiratory volume in one second after allergen challenge was significantly reduced by cromolyn in 15 of 17 subjects. Immediate and delayed reactions of itching, tightness, or wheezing developed in 14 subjects after allergen challenges following placebo intake and were prevented or substantially inhibited by cromolyn.

To evaluate the efficacy of antidiarrheal agents in the treatment of diarrheal illnesses, a study was conducted with children in Guatemala who had an acute diarrheal illness. Eighty patients, aged 3 to 11 years, were hospitalized and treated for two days with one of five agents: kaolin-pectin suspension concentrate (Kao-Con), kaolin suspension, pectin suspension, diphenoxylate-atropine liquid (Lomotil), or placebo. Although the patients receiving kaolin-pectin produced stools that tended to be more formed than those of the placebo-treated group patients, the study did not demonstrate any effect by any of the agents tested in influencing the frequency of bowel movement, the water content of the stools, or the weight of stools. Kaolin-pectin suspension and diphenoxylate-atropine liquid do not appear to be useful in the relief of acute nonspecific diarrhea in children.

One cannot now predict with accuracy the degree of deficit that may be anticipated following a carotid occlusion even when the condition of the opposite artery is known. When symptoms and signs occur, they are most likely related to the hemisphere or eye on the side of the occlusion. In patients with carotid occlusion, a higher rate of severe complications and mortality was encountered following arteriography than in the general study population. Among randomized patients with a carotid occlusion and a contralateral carotid stenosis, 63% of medically treated patients were alive at the end of a 66-month follow-up, whereas only 34% of surgically treated patients were still living. Surgical mortality was extremely high in patients with a carotid occlusion. Sixty-seven percent mortality occurred in patients undergoing surgery within one week of a cerebral infarction.

A long-term comparative field trial of three live, attenuated rubella vaccines (HPV-77 DE-5, HPV-77 DK-12, and Cendehill) was initiated in 1969 on the islands of Kauai and Hawaii in the state of Hawaii. Rubella hemagglutination-inhibition (HI) tests on prevaccination serum specimens from 7,931 children in the two study areas indicated an overall susceptibility to rubella of nearly 70%. The rates of seroconversion of 5,153 seronegative subjects to HPV-77 DE-5, HPV-77 DK-12, and Cendehill vaccine were 97.5%, 99.9%, and 99.8%, respectively. Over the subsequent four-year follow-up period, during which time natural exposure to rubella was minimal, the percent decline of geometric mean titers did not vary substantially among the three vaccine groups and measured about twofold for all three. A total of only 28 vaccines (0.7%) who seroconverted to one of the vaccines in 1969 lost all measurable antibody by 1974. Measurable antibody persisted in more than 98% of all vaccinees over the four-year period. Reinfection, thought possibly to be an important factor in maintaining titers, did not occur frequently in the study population and could not be related to outbreaks of disease.

The effect of low-dose heparin prophylaxis on venous thrombosis and bleeding after major elective surgery was studied in a prospective controlled study of 820 patients. The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine (125I) was reduced from 16.0% in the control group to 4.2% in treated patients. More important, the incidence of popliteal or femoral vein thrombosis was reduced from 2.9% to 1.0%. Prophylaxis resulted in a slight increase in bleeding-minor wound hematoma, mean volume of blood transfused, and a post-operative hematocrit fall in treated patients. However, increased bleeding was clinically minor, and prophylaxis was well tolerated.

In this double-blind, randomized study, 200 normal subjects received a three-day course of one of five treatment regimens: lincomycin hydrochloride monohydrate injection (sterile solution, 300 mg/ml) with two tablets of either placebo, a mixture of atropine sulfate and diphenoxylate hydrochloride (Lomotil), an aspirin-phenacetin-caffeine (APC) combination or the latter with codeine, or an injection of saline with two placebo tablets. Gastrointestinal irritation was most prominent in subjects receiving lincomycin with atropine-diphenoxylate and lincomycin with APC plus codeine (P less than .05). Decreased intestinal motility from atropine-diphenoxylate or codeine may increase the contact time between the lincomycin (or its metabolites) or some developing toxic substances and the mucosal epithelium. The use of atropine-diphenoxylate or codeine in treating lincomycin-induced diarrhea may be questionable.

Twenty-eight infants and children hospitalized for severe shigellosis were treated orally either with ampicillin trihydrate (100 mg/kg/day administered in divided doses every six hours) or with trimethoprim-sulfamethoxazole (trimethoprim, 10 mg; sulfamethoxazole, 50 mg/kg/day in divided doses every 12 hours) for five days. Four patients with ampicillin-resistant shigellae continued to have diarrhea and positive stool cultures during therapy. Patients with susceptible shigellae treated with ampicillin and all patients treated with trimethoprim-sulfamethoxazole responsed promptly and comparably within an average of 1.6 and 1.7 days, respectively, until stool cultures were negative, and 3.1 and 2.9 days, respectively, until diarrhea stopped. Patients with ampicillin-resistant shigellae responded to treatment with trimethoprim-sulfamethoxazole. It is concluded that trimethoprim-sulfamethoxazole is the best currently available drug for treatment of shigellosis in areas where multiple antibiotic resistance of shigellae is common.

Four hundred children with streptococcal pharyngitis were treated randomly with single injections in groups of 100 each (1) with 600,000 units of penicillin G benzathine, (2) 1.2 million units of penicillin G benzathine, (3) 600,000 units of penicillin G benzathine and 600,000 units of penicillin G procaine, or (4) 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine. Clinical response and severity of local reaction were judged in a double-blind manner at 24, 48, and 72 hours; throat cultures were taken then, and at 10, 21, and 42 days. Although the clinical response to 900,000 units of penicillin G benzathine and 300,000 units of penicillin G procaine was equal to 1.2 million units of penicillin G benzathine, the former cleared the streptococci more quickly, greatly reduced the incidence and severity of local reactions, and offered optimal therapy for streptococcal pharyngitis in the pediatric age group.

Nitrous oxide in a concentration of 35% has been shown to ameliorate the pain of acute myocardial infarction. This conclusion was reached on the basis of a double-blind study in 69 patients and a clinical study in an additional 42 patients. The use of nitrous oxide was not accompanied by hemodynamic changes or significant adverse reactions.