The Anturane Reinfarction Trial is a randomized, double-blind, multicenter clinical trial comparing sulfinpyrazone (200 mg four times a day) and placebo in the prevention of cardiac mortality among patients with a recent documented myocardial infarction. Results represent data accumulated on 1475 cligible patients entered 25 to 35 days after myocardial infarction and followed for an average of 8.4 months. The data reflect excellent randomization, compliance with therapy and tolerance of the drug. All 69 deaths were a cardiovascular nature (68 cardiac and one cerebrovascular). For cardiac deaths, the annual death rate was 9.5 per cent in the placebo group and 4.9 per cent in the sulfinpyrazone group, representing an observed reduction of 48.5 per cent (P = 0.018). The annual sudden-cardiac-death rate was 6.3 per cent for the placebo and 2.7 per cent for the sulfinpyrazone group, representing a 57.2 per cent reduction in sudden-cardiac-death rate (P = 0.015). Sulfinpyrazone appears to be effective in reducing cardiac deaths during the first year after myocardial infarction.

We conducted a prospective study in a prepaid primary-care practice (health-maintenance organization) of a system in which nurses and physician assistants used protocols, and compared the efficiency and costs of this "new-health-practitioner" protocol system to a physician-only nonprotocol system. In five months, we studied 472 patients with any of four common acute complaints--respiratory infections, urinary and vaginal infections, headache, and abdominal pain; a subset of 203 patients was randomly allocated between the two systems. In the new-health-practitioner system physician time per patient was reduced by 92 per cent, from 11.8 to 0.9 minutes, and average visit costs--including practitioner time and charges for laboratory tests and medications--were 20 per cent less (P = 0.01). We conclude that this protocol system saves physician time and reduces costs.

Industrial workers exposed to the organochlorine pesticide, chlordecone (Kepone), had signs of toxicity in several organs. The extent of toxicity was proportional to the levels of this chemical in the tissues. In 22 patients, chlordecone was eliminated slowly from blood (half time of 165 +/- 27 days--mean +/- S.E.M.) and fat (half time of 125 days, with a range of 97 to 177), chiefly in the stool. Output of chlordecone in bile was 10 to 20 times greater than in stool, suggesting that chlordecone is reabsorbed in the "ntestine. Cholestyramine, an anion-exchange resin that binds chlordecone, increased its fecal excretion by seven times. In a five-month trial, cholestyramine significantly accelerated elimination of chlordecone from blood, with a half life of 80 +/- 4 days (S.E.M.) (P less than 0.005) and fat (half life of 64 days, with a range of 52 to 85) (P less than 0.05). Cholestyramine offers a practical means for detoxification of persons exposed to chlordecone and possibly to other lipophilic toxins.

Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.

To examine the effects of leg exercise on insulin absorption from various injection sites, 125I-labelled rapid actin insulin (9 units) was injected subcutaneously into the leg, arm or abdomen of patients with insulin-dependent diabetes before one hour of intermittent leg (bicycle) exercise and on a resting, control day. Insulin disappearance from the leg increased by 135 per cent during the first 10 minutes of leg exercise (P less than 0.05) and remained 50 per cent above resting levels after 60 minutes (P less than 0.02). Leg exercise had no effect on insulin disappearance from the arm, but insulin disappearance from the abdomen was reduced during the post-exercise recovery period (P less than 0.02). As compared to leg injection, arm or abdominal injection reduced the hypoglycemic effect of exercise by 57 per cent (P less than 0.02) and 89 per cent (P less than 0.005), respectively. Leg exercise accelerates insulin absorption from the leg. Arm or abdominal injection avoids this acceleration during leg exercise and reduces exercise-induced hypoglycemia.

Overweight patients with uncomplicated essential hypertension were followed up biweekly for six months: 24 not receiving antihypertensive-drug therapy (Group I) and 83 on regular but inadequate (despite drug manipulation) antihypertensive-drug therapy (Group II). All patients in Group I and 57 randomly selected patients from group II (IIa) participated in a weight-reduction program. The remaining 26 from Group II (IIb) did not receive a dietary program. Salt intake was in the normal range in all three groups. All patients on the dietary program lost at least 3 kg (mean, 10.5 kg), and all but two showed a meaningful reduction in blood pressure; 75 per cent of Group I and 61 per cent of Group IIa returned to normal blood pressure. The weight and blood-pressure reductions were highly significant (P less than 0.001), were present in both sexes and all ages, and were directly associated. In Group IIb, no significant change in blood pressure or weight occurred (P greater than 0.30).

In a randomized, double-blind, placebocontrolled study to evaluate the efficacy of trimethoprim-sulfamethoxazole for the prevention of Pneumocystis carinii pneumonia, we studied 160 patients with cancer who were at high risk for this pneumonia over a two-year period. Seventeen of the 80 patients receiving a placebo acquired P. carinii pneumonitis, whereas none of the 80 given 150 mg of trimethoprim and 750 mg of sulfamethoxazole per square meter per day had the infection P less than 0.01). Bacterial sepsis, pneumonia other than that caused by P. carinii, acute otitis media, upper-respiratory-tract infections, sinusitis and cellulitis occurred less frequently in recipients of the drug than in the placebo group (P less than 0.01 in each case). Oral candidiasis was the only adverse effect ecountered from trimethoprim-sulfamethoxazole administration. The study shows the combination to be highly effective in the prevention of P. carinii pneumonitis.

We assessed aspirin prophylaxis against venous thromboembolism in a prospective, controlled, double-blind study of patients over 40 years of age, who had undergone total hip replacement. Radiographic phlebography was the diagnostic end point. Thromboembolism developed in 11 of 44 patients receiving aspirin, as compared to 23 of 51 receiving the placebo (P less than 0.03). Unexpectedly, this protection was limited to men. In four of 23 men on aspirin thrombi developed, as compared to 14 of 25 receiving placebo (P less than 0.01). Corresponding figures for women were seven of 21 versus nine of 26. Review of a similar group of patients receiving aspirin revealed significantly greater protection (P less than 0.03) in men (three of 15) than in women (15 of 27). These data establish statistically significant prophylaxis in men over the age of 40 by 600 mg of aspirin given twice daily. The absence of a protective effect in women remains unexplained.

Since the last comprehensive review of anticoagulation in acute myocardial infarction four additional randomized control trials have been reported. The overwhelming majority of all trials favored anticoagulation. Rates of thromboembolism were higher in the control, and hemorrhagic complications in the anticoagulated group. Pooling of all randomized control trials gives mean case fatality rates of 19.6% for the control and 15.4% for the anticoagulated group, a relative reduction of 21% (P less than 0.05 or less than 0.001, depending on the analytic method). Five of six randomized control trials reported "no effect" because the difference favoring anticoagulation was not statistically significant. However, sample sizes in these "negative" papers were too small to protect against missing a 21% reduction in true case fatality rate due to anticoagulation (beta greater than 0.10). All patients who present no specific contraindication should receive anticoagulants during hospitalization for infarction.

To provide a rational basis for pancreatic enzyme replacement therapy, we evaluated, in six patients with advanced pancreatic insufficiency, the effects of various treatment regimens on fecal fat and nitrogen balance and on duodenal recovery of ingested pancreatic enzymes after a solid test meal. The combination of cimetidine (an H2-receptor antagonist) and pancreatin, each given by mouth, produced significantly higher postprandial duodenal recoveries and concentrations of trypsin and lipase (P less than 0.05). Steatorrhea was reduced in all patients and abolished in four of the six. In the dosages used, neither enteric-coated enzymes nor supplemental neutralizing antacids were more effective than pancreatin alone in decreasing steatorrhea or improving duodenal enzyme delivery. Cimetidine may be a useful adjunct to oral pancreatic extract therapy in some patients with severe pancreatic insufficiency who fail to respond to pancreatic enzyme replacement alone.

We performed field trials in the course of an epidemic in Finland to learn whether Group A memingococcal capsular polysaccharide vaccine protects infants and young children from meningitis. The first trial involved 130,178 children between the ages of three months and five years; 49,295 children received the vaccine, 48,977 received a control Haemophilus influenzae Type b polysaccharide vaccine, and 31.906 remained unvaccinated. No cases of meningitis or sepsis caused by Group A meningococci were seen in the first year of observation among the children vaccinated with meningococcal vaccine whereas six occurred among those vaccinated with the H. influenzae vaccine and 13 among those not vaccinated. In the second trial 21,007 children of the same ages received the meningococcal vaccine. No cases caused by Group A occurred among those vaccinated, although five to seven would have been expected within the year. Meningococcal Group A vaccine appears efficacious in young infants and children.

From September, 1967, to January, 1974, a clinical trial was carried out by the WHO Melanoma Group to evaluate the efficacy of elective lymph-node dissection in the treatment of malignant melanoma of the extremities with clinically uninvolved regional lymph nodes. Treatment was prospectively randomized: 267 patients to excision of primary melanoma and immediate regional-lymph-node dissection and 286 to excision of primary melanoma and regional-lymph-node dissection at the time of appearance of metastases. The statistical analysis showed no difference in survival between the two groups of patients, regardless of how the data were analyzed (according to sex, site of origin, maximum diameter of primary tumor or Clark's level or Breslow's thickness). Elective lymph-node dissection in malignant malanoma of the limbs does not improve the prognosis and is not recommended when patients can be followed at intervals of three months.

We evaluated the effect of saphenous-vein-bypass grafting on survival in patients with chronic stable angina by comparing medical and surgical treatment in a large-scale, prospective randomized study. Excluding patients with left-main-coronary-artery disease who have already been reported, a total of 596 patients were entered into this study; when randomized into a medical group (310 patients) and a surgical group (286 patients), entry clinical and angiographic base lines were comparable. Operative mortality at 30 days was 5.6 per cent. At an average of one year after operation, 69 per cent of all grafts were patent, and 88 per cent of the surgical patients had atleast one patent graft. There was no statistically significant difference in survival, at a minimal follow-up interval of 21 months, between patients treated medically and those treated with saphenous-vein-bypass grafting. At 36 months, 87 per cent of the medical group and 88 per cent of the surgical group were alive.