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.

Kayser-Fleischer rings are pigmented corneal rings at the limbus of the cornea in Descemet's membrane that have been deemed pathognomonic of Wilson's disease. However, we have observed four exceptions in patients with non-Wilsonian liver disease. Three patients had primary biliary cirrhosis and one patient had chronic aggressive hepatitis with cirrhosis. Pigmented corneal rings were seen only by slit-lamp examination. Hepatic, serum, and urinary copper and serum ceruloplasmin levels were significantly elevated in the patients with primary biliary cirrhosis. Radiocopper (64Cu or 67Cu) studies in patients with primary biliary cirrhosis showed plasma disappearance curves which allowed a clear distinction from Wilson's disease in that all three patients with primary biliary cirrhosis showed a secondary rise in radiocopper that presumably represented copper incorporation into ceruloplasmin. In one patient, in whom 64Cu in ceruloplasmin was studied specifically, incorporation was found to be normal.

In a double-blind study of four patients with hereditary angioedema, the efficacy of methyltestosterone (taken daily in 10-mg linguet form) in preventing attacks was shown. There were 19 episodes during 11.8 months of placebo administration, compared with only four attacks during the 46 months of cumulative methyltestosterone treatment (P less than 0.001). The mean serum C4 protein level was twice as high in all patients when they were taking the drug (176 +/- 36 mug/ml) as compared with the placebo (84 +/- 21 mug/ml), and rose to normal range in three of four patients.

Investigators at 30 centers evaluated an intravenous hepatitis B immune globulin preparation in the therapy of fulminant type B hepatitis. Patients with serum positive for hepatitis B surface antigen were treated at stage II to stage IV of hepatic encephalopathy. A central computer program randomized cases for treatment with hyperimmune globulin or albumin placebo. During the first 6 months, the dose of hepatitis B immune globulin was 1.32 g of immunoglobulin G protein; during the last 7 months, it was 5.28 g. Neither dose eliminated antigenemia. In the placebo group, death occurred in four of eight cases randomized at stage II, five of eight at stage III, and 10 of 12 at stage IV. In the group treated with hyperimmune globulin, death occurred in three of five patients randomized at stage II, seven of 12 at stage III, and six of eight at stage IV. The study, therefore, showed no benefit of treatment with exogenous antibody.

Nine patients with familial Mediterranean fever (FMF) were admitted to a controlled, double-blind trial to determine if there are patients with this disease who are able to abort their acute episodes of pain and fever with short courses of colchicine taken at the onset of attacks. Five patients completed their treatment assignments, and colchicine was significantly effective in aborting the attacks of three but was ineffective in two. The remaining four patients could not be assessed because of insufficient numbers of courses. During the 10 months of the trial, 28 courses of colchicine and 31 of placebo were taken during the early stages of FMF attacks. Twenty-one (75%) colchicine courses were followed by attacks considered to have been aborted, compared to only three (10%) placebo courses. This trial shows that patients can recognize the prodrome of their FMF attacks and that some patients can consistently abort their attacks with short courses of colchicine taken at the very onset of symptoms.

Postprandila glycaemia and rise in serum insulin after carbohydrate-containing meals were reduced by the addition of guar flour or pectin, or both. After a liquid test meal (four subjects) the 30-min blood glucose was reduced from 6.33 +/- 0.19 mmol/litre (114 +/- mg/dl), mean +/- SEM, in the control subjects of 4.77 +/- 0.17 mmol/litre (86 +/- 3 mg/dl) by addition of guar gum (P less than 0.05). The mean insulin level was also significantly lower at 15 min. A breakfast test meal (bread, butter, marmalade, and tea) resulted in a mean 15-min blood glucose of 6.18 +/- 0.21 mmol/litre (111 +/- 4 mg/dl) in eight subjects; 10 g of pectin added to the marmalade reduced this level to 5.64 +/- 0.17 mmol/litre (102 +/- 3 mg/dl) (P less than 0.01). The insulin levels were significantly lower at 15, 30, and 45 min. A similar meal in which guar was added to the bread and pectin to the marmalade resulted in significant reductions of blood glucose at 15 min (P less than 0.002) and 30 min (P less than 0.01). The insulin values were also significantly lower throughout the first 90 min of the test. This action of unavailable carbohydrate may prove useful in the dietary control of diabetes.