The efficacy of inhaled beclomethasone dipropionate has been examined in 44 steroid-dependent asthmatics observed for 9 months to 2 years. A 3-month double-blind trial found that subjects treated with beclomethasone had a significant diminution in symptoms, were able to reduce their use of medication, and had improved maximum expiratory flow rates. Approximately one half were able to discontinue the use of oral prednisone within 9 months after starting beclomethasone, and a further one third reduced their dose by at least 50%. No characteristics could be defined to predict responsiveness to beclomethasone. The effectiveness of beclomethasone was sustained for as long as 2 years and was not associated with any abnormal urine, blood, or serum values or chest X-ray findings. Candidiasis of the palate appeared in approximately one third of the subjects and was usually transient. The chronic use of beclomethasone did not result in endocrine suppression.

Heat-stable, serum-derived chemotactic activity for neutrophils is shown in a human model of immunoglobulin E-mediated asthma. Twenty-six ragweed-sensitive subjects underwent bronchial provocation challenge using ragweed and Mecholyl. Increased neutrophil chemotactic activity was found in serum tested from 5 to 30 min after a positive ragweed-inhalation challenge, but not after negative ragweed challenge. The appearance of neutrophil chemotactic activity did not reflect the effects of bronchospasm alone, because it was not found after bronchospastic responses to Mecholyl in the same subjects. There were no accompanying changes of serum complement activity, nor evidence of inhibition of the chemotactic activity by proir exposure to antisera to the third and fifth components of complement. Ultrafiltration of serum showed chemotactic activity contained in fractions of at least 50 000 daltons. This appears to be the first demonstration of neutrophil chemotactic activity liberated during experimentally induced immunoglobulin E-mediated asthma in humans.

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.

Minocycline has proved to have a wider spectrum of activity against both aerobic and anaerobic bacteria and has enhanced tissue penetration when compared with its tetracycline congeners. The latter, and possibly the former, can be related to its increased lipophilicity in the physiologic pH range. It appears to be a superior chemoprophylactic agent against sulfonamide-resistant meningococci that do not become minocycline resistant as a result of treatment. The clinical promise of this agent has been dimmed, however, by recent reports of vestibular toxicity manifest in ambulatory patients. Though data on the frequency and severity of these symptoms are in some conflict, minocycline cannot currently be recommended for general clinical use.

Amantadine HCl administration has resulted in accelerated resolution of influenza A illness. Prolonged abnormalities in pulmonary function have been described in uncomplicated influenza A. To study the effect of amantadine on these changes, we evaluated young adults with documented natural influenza A with clear chest examinations and X rays. Subjects received placebo or amantadine in random, double-blind fashion. Physiologic studies included maximal expiratory flow volume curves with air and helium-oxygen mixtures. Air flow rates were unchanged in all subjects throughout. Initially, both groups showed comparable decreases in mean helium-oxygen maximal expiratory flow rates. The amantadine group showed accelerated physiologic improvement: significant increase in helium-oxygen flow rates occurred within 7 days (P less than 0.05). The rate of improvement in the helium-oxygen flow rates in the placebo group was not statistically significant. These studies confirm peripheral airways dysfunction after uncomplicated influenza A and suggest that amantadine is associated with accelerated resolution of this dysfunction.

The premise that measures used to lower the plasma lipids in patients with hyperlipidemia will lead to reductions in new events of coronary heart disease (the Lipid Hypothesis) should be reconsidered today as a result of several recent reports of large-scale double-blind drug trials in the United Kingdom and in the United States. To that end, the published evidence that bears on tests of the hypothesis by dietary and drug interventions is reviewed, and the conclusion reached that the hypothesis has not yet been adequately tested. A phased program is described that will prepare the ground for a fuller and more definitive trial of the premise in the future: the first steps must be to establish that a combined diet/drug regimen in large numbers of adult male hyperlipidemic patients is acceptable and essentially harmless and that during an observation period of several years a high rate of adherence to the regimen can be attained. Any advice to the general public to make large dietary changes now is considered premature.

SKin testing was done on 30 patients with a history of anaphylactic reactions after a Hymenoptera sting and on 30 control subjects. The patients all had positive basophilhistamine release to one or more venoms on challenge with the specific venoms used for skin testing (honey bee, yellow jacket, white-faced hornet, yellow hornet, and Polistes). At 0.1 mug of venom/ml and at 1.0 mug of venom/ml, 75% and 100%, respectively, of the sensitive patients had a positive skin test. There was a significant (P less than 0.001) correlation between skin test and histamine release results. Of the 150 skin tests in control patients, only 1 was positive. Venom skin tests provide, for the first time, a simple, readily available technique to accurately diagnose allergy to stinging insects.

To determine the effects of early ambulation on peripheral venous thrombosis in the coronary care unit, 29 patients with acute myocardial infarction had daily 125I-fibrinogen point counting of both legs using a standard portable technique in the first 3 to 7 days after admission. Twenty-one patients underwent early ambulation during the initial 3 days, while 8 remained at complete bed rest for 5 days. Only 2 of 21 early ambulated patients had positive fibrinogen point counts, in contrast to 5 of 8 nonambulated patients (P less than 0.01). With heart failure, only 2 of 9 ambulated patients had positive point counts, compared with 4 of 5 nonambulated patients (P less than 0.05). In 16 patients undergoing venography, point counts were confirmed in 6 positive and 10 negative findings. These results show that the high frequency of peripheral venous thrombosis in immobilized acute myocardial infarction patients, particularly those with heart failure, can be effectively reduced by early ambulation.

Physicians working at the General Medical Clinic of the Johns Hopkins Hospital entered into tutorials to improve their effectiveness as managers and educators of patients with essential hypertension. After exposure to a single teaching session, tutored physicians allocated a greater percent of clinic-visit time to patient teaching than did control physicians, achieving increased patient knowledge and more appropriate patient beliefs regarding hypertension and its therapy. Patients of tutored physicians were more compliant with drug regimens and had better control of blood pressure than patients of untutored physicians. The personal physician, if he is provided with strategies for identifying the noncompliant patient and for intervening in that behavior, can apply a stimulus to his patients that results in improved compliance and better control of hypertension.

The effect of low-dose intramuscular insulin therapy was compared with that of high-dose insulin therapy by intravenous and subcutaneous routes in 48 patients with diabetic ketoacidosis. A simplified protocol was devised to compare efficacy of the two methods of therapy in a randomized manner. Plasma glucose dropped to less than 250 mg/dl in the low-dose group in 6.7 +/- 0.8 h and in the high-dose group in 4.5 +/- 0.8 h (P = not significant). The amount of insulin necessary to lower plasma glucose to 250 mg/dl was 263 +/- 45 U in the high-dose group and 46 +/- 5 U in the low-dose group. Twenty five percent in the high-dose group and none in the low-dose group developed hypoglycemia. Other biochemical and clinical variables in the two groups were comparable. No treatment complications were noted in the low-dose group. Our studies suggest that low-dose intramuscular insulin therapy is simple and as effective as high-dose therapy in the treatment of diabetic ketoacidosis without the risk of hypoglycemia and with a diminished incidence of hypokalemia. Furthermore, the favorable response of these patients to low-dose insulin therapy suggests the absence of insulin resistance in diabetic ketoacidosis.

The effect of ingestion of a gelatin capsule containing 127 mug of 16,16-dimethyl prostaglandin E2 (DM-prostaglandin E2) or a liquid containing 127 mug of DM-prostaglandin E2 on stimulated gastric secretion in man was studied. DM-prostaglandin E2 significantly reduced the volume, acid concentration, and total acid output of gastric secretion. Secretory inhibition during the 3 h after treatment with the capsule was 37% (volume), 39% (acid concentration), and 60% (acid output). The DM-prostaglandin E2 capsule was nearly as effective as equivalent amount of DM-prostaglandin E2 in solution. Prostaglandin analogues, because of their oral effectiveness and duration of action, may have therapeutic value in peptic ulcer disease.

We evaluated the effect of ethanol on exercise performance until angina in 12 patients in a double-blind, randomized study. The mean resting heart rate times systolic blood pressure was not changed after Fresca but was increased after 2 ounces of ethanol (P less than 0.001) and after 5 ounces of ethanol (P less than 0.01). Compared to the control periods, the mean exercise time until angina was not different after Fresca but was decreased after 2 ounces of ethanol (P less than 0.001) and after 5 ounces of ethanol (P less than 0.001). Compared to the control periods, the mean maximal ischemic ST-segment depression after angina was not changed after Fresca but was increased after 2 ounces of ethanol (P less than 0.01) and after 5 ounces of ethanol (P less than 0.001). Drinking 5 ounces or 2 ounces of ethanol decreases exercise duration until angina and increases ischemic ST-segment depression after angina.