Between 1979 and 1984, 195 evaluable patients were entered in an international multicenter study comparing two regimens for patients with completely resected pathological Stage II testicular cancer (that is, with positive retroperitoneal lymph nodes). All patients had undergone orchiectomy and dissection of the retroperitoneal lymph nodes. They were randomly assigned to be treated with two cycles of immediate adjuvant cisplatin-based chemotherapy or to be observed monthly with treatment at relapse. The median follow-up period was four years. Of the 97 patients assigned to adjuvant chemotherapy, 6 (6 percent) had a recurrence; however, only 1 had received adjuvant chemotherapy before the recurrence. Three died (one of testicular cancer), and 94 of the 97 survived. Of the 98 patients who were observed, 48 (49 percent) had a relapse. However, almost all patients with relapses were effectively treated, and 93 of the 98 are alive and disease-free; 3 have died of testicular cancer. No identifiable factors were strongly associated with the risk of relapse. We conclude that two courses of cisplatin-based adjuvant chemotherapy will almost always prevent relapse in pathological Stage II testicular cancer treated with orchiectomy and retroperitoneal-lymph-node dissection. However, when surgery, follow-up, and chemotherapy are optimal, observation with chemotherapy only for relapse will lead to equivalent cure rates.

Gram-negative nosocomial pneumonia may result from retrograde colonization of the pharynx from the stomach, and this may be more likely when the gastric pH is relatively high. We studied the rate of nosocomial pneumonia among 130 patients given mechanical ventilation in an intensive care unit who were receiving as prophylaxis for stress ulcer either sucralfate (n = 61), which does not raise gastric pH, or conventional treatment with antacids, histamine type 2 (H2) blockers, or both (n = 69). At the time of randomization to treatment, the two groups were similar in age, underlying diseases, and severity of acute illness. Patients in the sucralfate group had a higher proportion of gastric aspirates with a pH less than or equal to 4 (P less than 0.001) and significantly lower concentrations of gram-negative bacilli (P less than 0.05) in gastric aspirates, pharyngeal swabs, and tracheal aspirates than did patients in the antacid-H2-blocker group. The rate of pneumonia was twice as high in the antacid-H2 group as in the sucralfate group (95 percent confidence interval, 0.89 to 4.58; P = 0.11). Gram-negative bacilli were isolated more frequently from the tracheal aspirates of patients with pneumonia who were receiving antacids or H2 blockers. Mortality rates were 1.6 times higher in the antacid-H2 group than in the sucralfate group (95 percent confidence interval, 0.99 to 2.50; P = 0.07). Although our results fell just short of statistical significance when they were analyzed according to intention to treat, they suggest that agents that elevate gastric pH increase the risk of nosocomial pneumonia in patients receiving ventilation by favoring gastric colonization with gram-negative bacilli. We conclude that in patients receiving mechanical ventilation, the use of a prophylactic agent against stress-ulcer bleeding that preserves the natural gastric acid barrier against bacterial overgrowth may be preferable to antacids and H2 blockers.

In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.

We performed a prospective, randomized, placebo-controlled, double-blind clinical trial of antibiotic administration to treat possible occult bacteremia in febrile children. A total of 955 children aged 3 to 36 months with temperatures greater than or equal to 39.0 degrees C and no focal bacterial infection were enrolled at the emergency departments of two children's hospitals from January 1982 until July 1984. Blood samples for culture were obtained, and the children were randomly assigned to receive either oral amoxicillin or placebo and were restudied approximately 48 hours after enrollment. Data were also collected on 228 children who could not be randomly assigned. Twenty-seven of the randomly assigned children (2.8 percent) had bacteremic infections with pathogenic organisms (Streptococcus pneumoniae, Haemophilus influenzae, and salmonella). There were no differences in the incidence of major infectious morbidity associated with bacteremia between the antibiotic and placebo groups--2 of 19 patients (10.5 percent) in the antibiotic group and 1 of 8 (12.5 percent) in the placebo group--although the power for this comparison was low. Antibiotics reduced fever (P less than 0.005) and improved the clinical appearance (P = 0.07) in the children with bacteremia but not in those without bacteremia. Although there were no statistically significant differences in the incidence of side effects, diarrhea tended to occur more often in the patients treated with amoxicillin (15 vs. 11 percent, P less than 0.10). We conclude that our data do not support the routine use of standard oral doses of amoxicillin in febrile children who do not have evidence of focal bacterial disease.

We conducted a pilot study followed by a large clinical trial in Nepal of the use of the capsular polysaccharide of Salmonella typhi (Vi) as a vaccine to prevent typhoid fever. In the pilot study, involving 274 Nepalese, there were no significant side effects of the Vi vaccine; about 75 percent responded with a rise in serum antibodies of fourfold or more. In the clinical trial, residents of five villages were given intramuscular injections of either Vi or, as a control, pneumococcus vaccine dispensed in coded, randomly arranged, single-dose syringes. There were 6907 participants, of whom 6438 were members of the target population (5 to 44 years of age); each was visited every two days. Those with temperatures of 37.8 degrees C or higher for three consecutive days were examined and asked to give blood for culture. Typhoid was diagnosed as either blood culture-positive or clinically suspected on the basis of bradycardia, splenomegaly, and fever, with a negative blood culture. Seventeen months after vaccination, the codes were broken for the 71 patients meeting the criteria for either culture-positive or clinically suspected typhoid. The attack rate of typhoid was 16.2 per 1000 among the controls and 4.1 per 1000 among those immunized with Vi (P less than 0.00001). The efficacy of Vi was 72 percent in the culture-positive cases, 80 percent in the clinically suspected cases, and 75 percent in the two groups combined. These data provide evidence that Vi antibodies confer protection against typhoid. Surveillance continues to determine the duration of Vi-induced immunity.

We undertook a prospective randomized trial to examine whether an intravenous cytomegalovirus (CMV) immune globulin would prevent primary CMV disease in renal-transplant recipients. Fifty-nine CMV-seronegative patients who received kidneys from donors who had antibodies against CMV were assigned to receive either intravenous CMV immune globulin or no treatment. The immune globulin was administered in multiple doses over the first four months after transplantation. The incidence of virologically confirmed CMV-associated syndromes was reduced from 60 percent in controls to 21 percent in recipients of CMV immune globulin (P less than 0.01). Fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20 percent of controls (P = 0.05). Only 4 percent of globulin recipients had marked leukopenia (reflecting serious CMV disease), as compared with 37 percent of the controls (P less than 0.01). There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17 percent of controls as compared with 4 percent of globulin recipients). A significant reduction in serious CMV-associated disease was observed even when patients were stratified according to therapy for transplant rejection (P = 0.04). We observed no effect of immune globulin on rates of viral isolation or seroconversion, suggesting that treated patients often harbored the virus but that clinically evident disease was much less likely to develop in them. We conclude that CMV immune globulin provides effective prophylaxis in renal-transplant recipients at risk for primary CMV disease.

Apache Indian infants have a high frequency of Haemophilus influenzae type b (Hib) and pneumococcal infections. Forty percent of Hib infections in these infants occur before the age of six months, when active immunization may not be protective. To evaluate the efficacy of passive immunization with a human hyperimmune globulin (bacterial polysaccharide immune globulin [BPIG]) prepared from the plasma of immunized adult donors, we randomly assigned 703 infants in a double-blind fashion to receive 0.5 ml of BPIG per kilogram of body weight (n = 353) or 0.5 ml of saline (n = 350) intramuscularly at 2, 6, and 10 months of age. Hib-antibody levels were significantly higher in BPIG recipients than in placebo recipients at 4, 6, and 10 months of age (P less than 0.001). During the first 90 days after BPIG or placebo injection, no Hib or pneumococcal infections were detected in the BPIG group, whereas seven Hib infections (six cases of bacteremia and one of meningitis) and four pneumococcal infections (bacteremia) were detected in the placebo group (P = 0.007 and 0.06, respectively). During the fourth month, one case of Hib meningitis and two cases of pneumococcal bacteremia developed in the BPIG group, whereas there were no Hib or pneumococcal infections in the placebo group. We conclude that BPIG given at four-month intervals provided significant protection against serious Hib disease for three months, and that in high-risk infants it might be used alone, perhaps at three-month intervals, or together with active immunization.

The x-ray contrast mediums used over the past three decades have been salts of iodinated acids administered in highly hypertonic concentrations. We conducted a multiinstitutional randomized study of the protective effects of pretreatment with corticosteroids against reactions to intravenous contrast material. We gave 6763 patients two doses of oral corticosteroids (methylprednisolone, 32 mg) approximately 12 hours and 2 hours before challenge with contrast material, one dose of oral prednisolone approximately 2 hours before challenge, or placebo in the same dosages. The two-dose corticosteroid regimen, but not the one-dose regimen, significantly reduced the incidence of reactions of all types (P less than 0.05) except a category of reactions dominated by hives, for which the reduction approached significance (P = 0.055). In recent years, several relatively expensive monomeric nonionic iodinated compounds having approximately half the osmolality of the corresponding ionic compounds and a lower reaction rate have become available. With our two-dose corticosteroid regimen, the incidence of reactions necessitating therapy in patients receiving the ionic medium approximated that reported in an unblinded nonrandomized study of patients receiving a newer intravenous nonionic medium without corticosteroid pretreatment. We conclude that the much less expensive ionic medium, if administered with corticosteroid pretreatment, may serve as a reasonable alternative to intravenous nonionic medium, without loss of safety.

We conducted a prospective, randomized, multicenter, single-blind trial of propranolol as compared with placebo in the prevention of first upper gastrointestinal tract bleeding in patients with cirrhosis of the liver. A total of 230 patients (90 percent with alcoholism and 46 percent with a Child-Pugh grade C classification) with large esophageal varices without previous bleeding were randomly assigned to receive either propranolol (n = 118) or placebo (n = 112), after they had been divided into two groups according to the severity of their liver disease. The end points of the study were bleeding and death. The dose of propranolol was progressively increased to decrease the heart rate by 20 to 25 percent. The final doses were 40 mg of conventional propranolol and 160 and 320 mg of long-acting propranolol daily in 22 percent, 60 percent, and 18 percent of patients, respectively. The mean (+/- SD) follow-up time among survivors without bleeding was 436 +/- 172 days. The cumulative percentages of patients free of bleeding two years after inclusion in the study were 74 percent (95 percent confidence limits, 61 and 83) in the propranolol group and 39 percent (95 percent confidence limits, 15 and 69) in the placebo group (P less than 0.05). Cumulative two-year survival was 72 percent (95 percent confidence limits, 60 and 81) in the propranolol group and 51 percent (95 percent confidence limits, 37 and 64) in the placebo group (P less than 0.05). The advantage of propranolol over placebo was maintained when potentially confounding variables were adjusted with use of the Cox model. Side effects occurred in 17 percent of the patients who received propranolol and led to the stopping of treatment in 11 percent. We conclude that propranolol can decrease the incidence of first bleeding and death during a period of two years in patients with cirrhosis and large varices.

In a double-blind trial of streptokinase for acute myocardial infarction, 219 consecutive patients presenting with infarction within four hours (mean, 3.0 +/- 0.8) of the onset of chest pain were randomly assigned to treatment with streptokinase (1.5 million units) or placebo, given intravenously over 30 minutes. The primary end point of the study was left ventricular function in patients with first infarctions. Patients who could undergo beta-blockade also received intravenous propranolol. Heparin (for 48 hours) and a combination of low-dose aspirin and dipyridamole were administered to both groups until cineangiography was performed at three weeks. In the patients with first infarctions treated with streptokinase, the left ventricular ejection fraction was 6 percentage points higher (streptokinase vs. placebo, 59 +/- 10.5 vs. 53 +/- 13.5 percent; P less than 0.005), with benefit to patients with either anterior infarction (57 +/- 11.9 vs. 49 +/- 15.9 percent; P less than 0.05) or inferior infarction (60 +/- 9.1 vs. 55 +/- 11.3 percent; P less than 0.05). Left ventricular function was improved regardless of whether concomitant propranolol was given. Survival (at 30 days) was improved with streptokinase: 2 deaths occurred among 79 patients who received this drug, as compared with 12 deaths among 93 patients who received placebo (2.5 vs. 12.9 percent, P = 0.012). Rates of reinfarction (streptokinase vs. placebo, 3 vs. 1 percent) and requirements for surgery or angioplasty (7 vs. 5 percent) were similar in the two groups. We conclude that administration of intravenous streptokinase (1.5 million units) to patients with a first myocardial infarction results in improved left ventricular function and short-term survival.

Sixty volunteers with insomnia participated in a randomized, double-blind, controlled clinical trial. After an initial six nights of placebo, 30 subjects (the abrupt-withdrawal group) received 0.5 mg of triazolam nightly for 7 to 10 nights, after which they received placebo. The other 30 subjects (the tapered-dosage group) received the same initial placebo treatment, then triazolam at 0.5 mg for seven nights, at 0.25 mg for two nights, and at 0.125 mg for two nights, and then placebo. As compared with the initial placebo period, the triazolam period significantly reduced the interval before the onset of sleep (sleep latency), and it prolonged sleep duration, reduced the number of awakenings, and improved the self-rated soundness of sleep in all cohorts. In the abrupt-withdrawal group, plasma levels of triazolam were undetectable the morning after the first night of placebo substitution, and subjects reported prolongation of sleep latency (57 minutes longer than base line), reduction in sleep duration (1.4 hours less than base line), and increased awakenings (1.2 per night above base line). The symptoms of rebound sleep disorder lasted one or possibly two nights, and there was a reversion toward base line on subsequent placebo nights. In the tapered-dosage group, however, plasma triazolam levels fell gradually to zero, and rebound symptoms were decreased or eliminated. Thus, rebound sleep disorder following abrupt discontinuation of triazolam can be attenuated by a regimen of tapering.

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.

We conducted a multicenter randomized, double-blind, placebo-controlled trial of early short-term, high-dose methylprednisolone sodium succinate in 223 patients with clinical signs of systemic sepsis and a normal sensorium (112 received glucocorticoid and 111 placebo). Patients also received antibiotics and intravenous fluids. Glucocorticoid or placebo was administered intravenously by a bolus (30 mg per kilogram of body weight over 15 minutes) followed by infusion of 5 mg per kilogram per hour for nine hours. The average time between the diagnosis of sepsis and infusion was 2.8 hours. The principal end point was 14-day mortality, which was similar in the placebo (22 percent) and glucocorticoid (21 percent) groups (P = 0.97). Mortality was also not significantly different between those receiving placebo and those receiving glucocorticoid in subgroups with evidence of sepsis (21 vs. 19 percent), gram-negative bacteremia (27 vs. 7 percent), gram-positive bacteremia (18 vs. 26 percent), or all gram-negative infections (25 vs. 17 percent). Resolution of secondary infection within 14 days was significantly higher in patients receiving placebo (12 of 23) than in those receiving glucocorticoid (3 of 16) (P = 0.03), but mortality rates were similar in both treatment groups for those with unresolved infection (36 vs. 31 percent). We conclude that early high-dose glucocorticoid therapy does not reduce mortality significantly in patients with systemic sepsis who have a normal sensorium, and therefore should not be used as adjunctive therapy.

We compared the efficacy of immediate coronary angioplasty after acute myocardial infarction with that of elective angioplasty at 7 to 10 days in patients treated initially with intravenous tissue plasminogen activator. The plasminogen activator (150 mg) was administered 2.95 +/- 1.1 hours after the onset of symptoms, to 386 patients with acute myocardial infarction. Ninety minutes later, patency of the coronary artery serving the area of the infarct was demonstrated by coronary angiography in 288 patients (75 percent). Bleeding problems were frequently encountered, as evidenced by an average drop in hematocrit of 11.7 +/- 6.5 points from base line to nadir and by a need for transfusion not related to bypass surgery in 70 patients (18 percent). After successful thrombolysis, 197 patients with a patent but severely stenotic vessel suitable for angioplasty were randomly assigned to immediate angioplasty (n = 99) or, if indicated 7 to 10 days after infarction, to deferred (elective) angioplasty (n = 98). The incidence of reocclusion was similar in the two groups: 11 percent in the group assigned to immediate angioplasty and 13 percent in the group assigned to elective angioplasty. Neither group had a significant improvement in global left ventricular function, and regional wall motion in the infarct zone improved to a similar extent in the two groups. In the elective-angioplasty group, the rate of crossover to emergency angioplasty for recurrent ischemia was 16 percent (whereas 5 percent of the immediate-angioplasty group required emergency repeated angioplasty; P = 0.01). In 14 percent of the patients in the elective group, the stenosis was substantially reduced by the time of the seven-day follow-up angiography, obviating the need for angioplasty. We conclude that in patients with initially successful thrombolysis and suitable coronary-artery anatomy, immediate angioplasty offers no clear advantage over delayed elective angioplasty.

Whether ingested calcium is absorbed more efficiently from freely water-soluble calcium salts than from poorly soluble salts is unclear. It is also unknown whether calcium is absorbed better from dairy products than from calcium salts. Using a method by which the net absorption of calcium can be accurately measured after a single dose, we studied eight healthy fasting subjects after they took a 500-mg dose of calcium from each of five calcium salts with various degrees of water solubility and from milk. The order of administration of the agents given was randomly determined. The mean (+/- SEM) net calcium absorption, in decreasing order of the solubility of the salts, was 32 +/- 4 percent from calcium acetate, 32 +/- 4 percent from calcium lactate, 27 +/- 3 percent from calcium gluconate, 30 +/- 3 percent from calcium citrate, and 39 +/- 3 percent from calcium carbonate. The differences in absorption were not statistically significant according to analysis of variance. On the basis of in vitro solubility experiments in acid mediums, we hypothesize that acid dissolution in the gastrointestinal tract may be responsible for the similar absorption of calcium from salts with widely different water solubilities. Calcium absorption from whole milk (31 +/- 3 percent) was similar to absorption from calcium salts. We conclude that calcium absorption from carbonate, acetate, lactate, gluconate, and citrate salts of calcium, and from whole milk, is similar in fasting healthy young subjects. Further study will be required to determine whether the results would be different in older subjects, with a higher dose of calcium, or if the calcium was ingested with food.

Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher--27 as compared with 16 percent--whereas the incidence of toxic effects for the two regimens was similar--44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P less than 0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy.

We conducted a double-blind, placebo-controlled trial of the efficacy of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) manifested by Pneumocystis carinii pneumonia alone, or with advanced AIDS-related complex. The subjects were stratified according to numbers of T cells with CD4 surface markers and were randomly assigned to receive either 250 mg of AZT or placebo by mouth every four hours for a total of 24 weeks. One hundred forty-five subjects received AZT, and 137 received placebo. When the study was terminated, 27 subjects had completed 24 weeks of the study, 152 had completed 16 weeks, and the remainder had completed at least 8 weeks. Nineteen placebo recipients and 1 AZT recipient died during the study (P less than 0.001). Opportunistic infections developed in 45 subjects receiving placebo, as compared with 24 receiving AZT. The base-line Karnofsky performance score and weight increased significantly among AZT recipients (P less than 0.001). A statistically significant increase in the number of CD4 cells was noted in subjects receiving AZT (P less than 0.001). After 12 weeks, the number of CD4 cells declined to pretreatment values among AZT recipients with AIDS but not amonG AZT recipients with AIDS-related complex. Skin-test anergy was partially reversed in 29 percent of subjects receiving AZT, as compared with 9 percent of those receiving placebo (P less than 0.001). These data demonstrate that AZT administration can decrease mortality and the frequency of opportunistic infections in a selected group of subjects with AIDS or AIDS-related complex, at least over the 8 to 24 weeks of observation in this study.

Thyroid nodules are present in up to 50 percent of adults in the fifth decade of life. Patients are often treated with thyroxine in order to reduce the size of the nodule, but the efficacy of thyrotropin-suppressive therapy with thyroxine remains uncertain. In this study, 53 patients with a colloid solitary thyroid nodule confirmed by biopsy were randomly assigned in a double-blind manner to receive placebo (n = 25) or levothyroxine (n = 28) for six months. Before treatment, pertechnetate-99m thyroid scanning showed that 22 percent of the nodules were functional, 25 percent hypofunctional, and 53 percent nonfunctional. High-resolution (10-MHz) sonography was used to measure the size of the nodules before and after treatment. Suppression of thyrotropin release was confirmed in the levothyroxine-treated group by the administration of thyrotropin-releasing hormone; thyrotropin release was normal in the placebo group. Six months of therapy did not significantly decrease the diameter or volume of the nodules in the levothyroxine group as compared with the placebo group. We conclude that the efficacy of levothyroxine therapy in reducing the size of colloid thyroid nodules is not apparent within six months, despite effective suppression of thyrotropin.

We conducted a prospective, randomized clinical trial over a two-year period in patients with acute lymphocytic leukemia to assess the effectiveness of trimethoprim-sulfamethoxazole given on three consecutive days each week as compared with daily in the prevention of Pneumocystis carinii pneumonitis. P. carinii pneumonitis did not develop in any of 92 patients receiving the drug daily (30,602 patient-days) or in any of 74 who received it three consecutive days a week (27,329 patient-days), whereas the incidence of the infection expected without prophylaxis is 21 percent. One patient, excluded from both groups because of an adverse reaction to sulfonamides in the past, acquired P. carinii pneumonitis. Especially noteworthy was a difference in the occurrence of systemic mycoses, with 10 cases in the daily-treatment group and only 1 case in the three-days-a-week group (P = 0.024). No differences were observed in the rates of other infections or adverse effects associated with the drug. We conclude that trimethoprim-sulfamethoxazole is as effective given three days a week as it is given daily in the prevention of P. carinii pneumonitis and that the intermittent schedule has the advantages of less frequent fungal infections and lower cost. Intermittent chemoprophylaxis may be especially beneficial to certain patients who are unable to tolerate the daily doses.