We have treated seven patients with severe psoriasis with sham or true hemodialysis. Three patients received one 24-h course of true hemodialysis over 4 d followed by an identical 24-h course 4 weeks later. Four patients received one 24-h course of sham diaglysis over 4 d followed by a 24-h course of true dialysis 4 weeks later. Significant subjective improvement was noted by both groups after the first series of treatments but not after the second. No objective improvement in skin disease was found at any time. We were unable to confirm the many uncontrolled reports on the efficacy of dialysis in ameliorating severe psoriasis. Neither the heparin used for anticoagulation, the acetate present in the dialysis bath, nor the removal of a "psoriatic factor" seemed to affect the skin disease in these patients.

Under randomized double-blind conditions, 1.00 to 1.67 mg of intravenous physostigmine (Antilirium) reversed sleep induced by administration of 0.102 to 0.238 mg/kg body weight of intravenous diazepam in eight healthy human volunteers. Awakening occurred 330 to 740s after initiation of the physostigmine infusion at a rate of 0.5 mg/min every 4 min. Diazepam plasma levels were not significantly different at the start of either the physostigmine or placebo infusion. Physostigmine did not effect plasma binding of diazepam. Six subjects experienced nausea, and one subject developed an arrhythmia. Physostigmine reverses diazepam-induced hypnosis but causes side-effects requiring cautious administration.

One hundred twenty-eight alcoholic men were assigned randomly to receive either a regular dose of disulfiram (250 mg), a pharmacologically inactive dose (1 mg), or no disulfiram. There were no statistically significant differences among the three treatment groups in total abstinence, percentage of drinking days, days worked, family stability (living with same relative), or percent of scheduled appointments kept. However, 21% of those who received the regular dose of disulfiram and 25% who received the pharmacologically inactive dose remained abstinent, whereas only 12% of those who received no disulfiram did so. These results indicate that disulfiram may be of limited value in the treatment of alcoholism, fear of the disulfiram-ethanol reaction is important in preventing drinking, and patients willing to take disulfiram are more likely to be abstinent if given the drug. We also found that complete abstinence correlated significantly with compliance and obtaining employment.

The effect of hypertonic (50%) glucose injected for relief of hemodialysis-induced muscular cramps was studied in 15 chronically uremic, nondiabetic patients who experienced a total of 44 cramp episodes. In a double-blind trial either 50 mL (or less) of hypertonic glucose or physiologic (0.9%) saline solution was injected, and the therapeutic response was evaluated. Of a total of 44 episodes of cramps, 26 were treated with hypertonic glucose and 18 with normal saline. Treatment with hypertonic glucose relieved 17 of 26 episodes, in contrast to only five of 18 episodes relieved with 50 mL of normal saline (P less than 0.016). No complications related to hypertonic glucose administration were observed. Hypertonic glucose seems to be safe and effective for the relief of dialysis-induced cramps. It also avoids undesirable loading with sodium and mannitol, which have been suggested for treatment of dialysis-induced cramps.

Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.

Daily change of intravenous (i.v.) infusion administration sets has been recommended by the Center for Disease Control since 1973 to reduce the risk of infusion bacteremia. To evaluate this recommendation, we undertook a prospective, randomized, controlled trial that compared the rates of i.v.-associated bacteremia, in-use i.v. fluid contamination, and phlebitis in 300 patients whose administration sets were changed every 24 h with those in 300 patients whose administration sets were changed every 48 h. No i.v.-associated bacteremia occurred. Twelve of 600 infusions (2%) had positive infusion-fluid cultures: five in one group and seven in the other. Both groups had comparable rates of phlebitis. In this study population with low rates of fluid contamination, no benefit accrued from changing the administration sets every 24 h instead of every 48 h. In hospitals with low rates of fluid contamination, the routine changing of i.v. administration sets every 48 h will result in substantial financial savings.

We compared low-dose insulin regimens in a prospective randomized trial in 30 patients with diabetic ketoacidosis. One group received a loading dose of 0.44 U/kg body weight of regular insulin half intramuscularly and half intravenously followed by 7 U/h intramuscularly, whereas the other group received a loading dose of 0.44 U/kg intravenously followed immediately by a constant infusion of 7 U/h in albumin-free saline. The time for metabolic control of the ketoacidosis was not significantly different in the two groups. Five patients in each group developed mild hypokalemia (serum potassium, 3.0 to 3.4 meq/litre). No patient became hypoglycemic, and there were no deaths within the follow-up period (24 h). In the treatment of diabetic ketoacidosis, low doses of insulin administered by the priming dose-intermittent intramuscular route are as effective as the constant infusion method.

Laminar air flow isolation and decontamination procedures were evaluated in a prospective randomized study in patients with aplastic anemia or acute leukemia undergoing marrow transplantation from HLA-matched siblings. Patients transplanted in the laminar air flow group had significantly less septicemia and major local infections than did patients in the control group. Nineteen of 46 laminar air flow patients and six of 44 control patients are alive at present. In patients with aplastic anemia the survival was 13 of 17 in the laminar air flow group compared with four of 17 in the control group. In patients with acute leukemia the survival was six of 29 in the laminar air flow group versus two of 27 in the control group. These differences were not statistically significant. Death in both the laminar air flow and control groups was predominantly due to interstitial pneumonitis or recurrent leukemia, which were unaffected by isolation and decontamination.

Alcoholism is a frequent complication of methadone treatment and is one of the few behaviors found to correlate with methadone treatment failure. To eliminate drinking among severely alcoholic patients, we tested the efficacy of incorporating methadone into a behavioral contingency to reinforce disulfiram ingestion. Methadone was dispensed to alcoholic narcotic addicts contingent upon their ingesting disulfiram, and as a control patients were urged to take disulfiram but received methadone regardless of whether they took disulfiram. The results indicated that the reinforced disulfiram treatment was highly successful in controlling alcoholism. In addition, nonstatistically significant trends suggested that the reinforced disulfiram treatment resulted in a superior adjustment, as reflected in arrest rate, unemployment, and illicit drug use. There appeared to be no significant physiologic or behavioral adverse effects.

A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.

Forty-seven patients with cholestatic jaundice were evaluated for extrahepatic biliary obstruction by ultrasonic cholangiography and the results verified by contrast cholangiography, celiotomy, or autopsy. Sonograms were evaluated both with ("official" reading) and without ("blind" reading) clinical information. By showing dilated bile ducts, sonography correctly diagnosed extrahepatic obstruction in 26 of 30 patients on "official" reading and 23 of 30 on "blind" reading. In all 17 patients without extrahepatic obstruction, sonography revealed the absence of dilated bile ducts. Among patients with extrahepatic obstruction, those with larger bile ducts had higher bilirubin concentrations, longer duration of jaundice, and were more reliably detected by sonography. In these patients, 94% with total bilirubin concentration greater than 10 mg/dl were detected by sonography, while 47% with total bilirubin concentration less than 10 mg/dl were detected. Although we recognize the limited sensitivity of sonography in early extrahepatic obstruction, we find it to be a valuable screening test in cholestatic jaundice.

Since both propranolol therapy and saphenous-vein bypass surgery have become accepted treatments for patients with symptomatic coronary-artery disease, it is important to determine if either influences the prevalence of ventricular arrhythmias in these patients. Six-hour dynamic electrocardiography was done on 130 patients with chronic stable angina pectoris at least 1 year after being randomized to surgical or medical therapy. All surgical patients had saphenous-vein grafting; 90% of the medical patients received propranolol. Data analysis showed that even though the overall prevalence of premature ventricular contractions was no different in medical and surgical patients, the prevalence of complex premature ventricular contractions was significantly higher in surgically treated patients not receiving propranolol than in propranolol-treated medical patients (p less than 0.05). However, the survival rate was no different in either group, and the quality of life in the surgical patients remained superior.

1,25 dihydroxycholecalciferol [1,25(OH)2D3] was studied in a double-blind controlled fashion in patients on chronic dialysis. Serum calcium was unchanged in 16 patients on vitamin D3 (D3) (400 to 1200 IU/day). In 15 patients on 1,25(OH)2D3 (0.5 to 1.5 microgram/day), serum calcium increased from 9.05 +/- .15 to 10.25 +/- .20 mg/dl (p less than 0.001), returning to 9.37 +/- .16 mg/dl (p less than 0.001) in the post control period. Patients on D3 showed no reversible decrease in immunoreactive parathyroid hormone levels, but patients on 1,25(OH)2D3 did, from a control of 1077 +/- 258 to 595 +/- 213 microliter equivalents/ml (p less than 0.01), and returned to 1165 +/- 271 microliter equivalents/ml (p less than 0.005). Nine of 12 patients on D3 who underwent serial iliac-crest biopsies showed histologic deterioration, and six of seven who received 1,25(OH)2D3 were improved or unchanged (p less than 0.025). Bone mineral and calcium decreased in patients on D3 (p less than 0.05) but not in those on 1,25(OH)2D3. Hypercalcemia occurred in five of 15 patients. We conclude that 1,25(OH)2D3 has a calcemic effect in chronic dialysis patients, decreases levels of immunoreactive parathyroid hormone, and is associated with histologic improvement in bone disease. Thus, 1,25(OH)2D3 is a valuable adjunct to the management of renal osteodystrophy but requires monitoring of serum calcium to avoid hypercalcemia.

We studied 24 healthy young male smokers to ascertain the medical safety of a highly effective smoking-abatement technique called rapid smoking. In comparison with results obtained after a 12-h cigarette fast or after normal smoking, statistically significant increases occurred after rapid smoking in heart and respiratory rates, systolic blood pressure, carboxyhemoglobin, and pH (p less than 0.05), while arterial PCO2, HCO3-, and serum [K+] fell (p less than 0.05). Rapid smoking produced alveolar hyperventilation in all subjects. In eight, arterial PO2 increased appropriately, but in 16, fell paradoxically (p less than 0.01); seven had arterial PO2 below 80 torr. Because this fall could represent ventilation/perfusion mismatch due to early bronchoconstrictive disease, in subjects with normal flow/volume loops and spirometry rapid smoking may be a simple, provocative screening test for early airway disease. Despite the changes produced there were no arrhythmias. Rapid smoking is safe for healthy subjects but should not now be used for higher-risk patients.

Eight patients with insulin-requiring diabetes were given, in random order, a diet containing 3 g and one containing 20 g of crude fiber. Each diet was maintained for 10 days and was the same in calories, carbohydrate, fat, and protein. Insulin dose was kept constant. Mean plasma glucose on the low-fiber diet was 169.4 +/- 11.7 mg/dl, significantly higher (P less than 0.001) than the value of 120.8 +/- 10.1 on the high-fiber diet. Hypoglycemic reactions were more common on the high-fiber diet. Weight remained essentially constant on both diets. Mean serum glucagon level on the high-fiber diet was significantly lower (P less than 0.001) than on the low-fiber diet, while serum free insulin levels were unchanged. These data indicate that substantial changes in fiber content of the diabetic diet may lead to marked changes in diabetic control and that increasing dietary fiber may be a useful means of lowering plasma glucose in some diabetic patients.

Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.

Sixty postmenopausal women were placed in three groups--control, sex hormone-treated, and CaCO3-treated--and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective.

Aspirin alters the gastric mucosal barrier as measured by ionic flux and potential difference. The effect of cimetidine on aspirin-induced alterations in gastric mucosa was studied in five normal male volunteers. Aspirin effects were studied with and without previous treatment with cimetidine. Mean (+/- SEM) basal potential difference was -48 +/- 1 mV. After 600 mg of aspirin in 1 dl of isotonic saline, potential difference decreased in 10 min to -39 +/- 1 mV (P less than 0.001) and returned to baseline within 60 min. Control biopsies showed 2% damaged mucosal cells compared with 20% damaged at the time of maximal drop in potential difference (P less than 0.001) after aspirin. Recovery to 9% damage occurred by 60 min. In subjects pretreated with 300 mg cimetidine, potential difference rose during 1 h to -62 +/- 1 mV (P less than 0.001). After aspirin potential difference fell to -48 +/- 1 mV compared with -39 +/- 1 mV with aspirin alone (P less than 0.01) and returned to -62 +/- 1 mV at 60 min. The cimetidine-treated group showed 4% mucosal damage at the peak potential difference fall after aspirin, significantly less (P less than 0.02) than in the untreated subjects.

To characterize the immunogenicity of influenza vaccine in patients with malignant disease, 21 patients with lymphoreticular neoplasms and 21 patients with solid tumors were immunized with inactivated influenza A/New Jersey/76 whole virus vaccine. The patients were randomized with respect to time of vaccine administration in relation to administration of chemotherapy. Fourfold or greater antibody titer increases occurred in 94% of controls and 71% of cancer patients (P less than 0.05), and the magnitude of antibody response was also significantly lower in cancer patients (P less than 0.01). There was no correlation of antibody responsiveness with sex, age, tumor type, absolute lymphocyte count, disease status, or type of chemotherapeutic agent used. Fifty percent of patients immunized at the time of chemotherapy administration showed seroconversion, which is significantly less than the 93% response rate observed in patients immunized between chemotherapy courses. It is thus recommended that individuals with malignant disease should receive influenza immunization between chemotherapy courses.

Folate deficiency is a frequent cause of anemia in alcoholics, but little attention has been paid to its prevention. Folic acid was readily soluble in wines of high ethanol content at concentrations of 10 microgram/ml. Lactobacillus casei folate activity of folic acid added to wines was well maintained during a month's storage at room temperature and fell to 61% to 66% of original activity after 3 months. Pteroylglutamic acid, 10 microgram/ml, added to wines and given in doses of the beverages (4 ml/kg body weight that caused inebriation, was well absorbed by six normal human volunteers (mean maximal increment in serum folate concentration +/- SEM, 71 +/- 8 ng/ml) and by seven recently intoxicated chronic alcoholics (mean increment, 94 +/- 4 ng/ml). Folate deficiency in alcoholics could be prevented by the fortification of alcoholic beverages with the vitamin.