Two insulin-requiring diabetics with isolated hyporeninemic hypoaldosteronism cpontaneously developed hyperkalemia that was aggravated whenever blood glucose concentration rose. Acute glucose infusions raised the serum potassium concentration in these patients with combined insulin and aldosterone deficiency but lowered, or did not change, the serum potassium concentration in normal subjects and in patients with either aldosterone or insulin deficiency alone. The paradoxical hyperkalemic response to glucose in patients with combined hormonal deficiency was blunted by prior administration of desoxycorticosterone acetate and abolished by prior administration of insulin. Our studies emphasize the crucial roles played by insulin and aldosterone in regulating the serum potassium concentration in man, and the need to avoid hyperglycemia in patients with combined insulin and aldosterone deficiency.

Oxazepam (Serax) is a tranquilizer-sedative of the benzodiazepine group that is predominantly metabolized to a pharmacologically inactive glucuronide and subsequently excreted by way of the kidneys. We administered this drug as a single oral dose to seven patients with acute viral hepatitis, to six with cirrhosis, and to age-matched control subjects. Elimination half-life (T1/2) and the apparent oral plasma clearance for the drug in patients with hepatitis and cirrhosis were comparable to values obtained in age-matched controls (P greater than 0.05). In addition, the apparent volume of distribution of oxazepam, its plasma binding, blood/plasma ratio, and the rate of urinary excretion of oxazepam, predominantly as the glucuronide, were comparable (p greater than 0.05) in the two groups of patients with liver disease and their respective controls. Unlike many other sedatives, oxazepam is eliminated normally in patients with parenchymal liver disease an therefore, on pharmacokinetic grounds, seems to be an excellent sedative for use in such persons.

The leukotactic function of patients with sarcoidosis was studied. A defect was found in 19 of the 20 patients tested and was due to moderately elevated serum levels of the chemotactic factor inactivator. The chemotactic factor inactivator levels were not as high as those previously reported in patients with Hodgkin's disease or cirrhosis of the liver. The effect of the inactivator was irreversible and was directed toward all three of the chemotactic factors tested. The physicochemical characteristics of chemotactic factor inactivator in serum from sarcoid patients resembled in most respects the features of chemotactic factor inactivator in normal serum. As expected, the generation of chemotactic activity in some sarcoid serums by zymosan was impaired. The results of this study may relate to some of the reported defects in expression of immunity in sarcoid patients.

One half of 42 subjects treated for painful shoulders received classic acupuncture, and one half received a placebo in which the needles did not penetrate the skin. Half of each of these groups was treated in a positive setting to encourage the subject, and half in a negative setting designed to keep encouragement at a minimum. All patients were independently rated for susceptibility to hypnosis. Although range of motion did not improve, the majority of patients reported significant improvement in shoulder discomfort to a blind evaluator after treatment; placebo and acupuncture groups did not differ in this respect, however. The positive and negative settings did not affect treatment outcome. In all groups, those who were not rated as highly susceptible to hypnosis tended to fail to achieve the highest levels of relief, but such differences were not statistically significant.

To assess the prevalence and distribution of allergic skin-test reactions in a general population sample, allergy prick tests were applied to 3101 subjects older than 2 years of age. Test materials included allergens common to the Tucson environment, and subjects were randomly stratified by age, sex, and socioeconomic status. No difference in the prevalence of measurable reactions was found among male subjects versus female subjects. A definite age relation was apparent, however, with the peak prevalence of reactivity (more than 40%) occurring during the third decade, and falling rapidly past age 50. When present, reactions tended to be multiple, highly reproducible, and more frequent among those in the higher socioeconomic strata. The prick test was judged to be a useful tool for the assessment of atopy.

A lipid intervention clinic screened 4000 employees (89% participation) and identified 150 type IV subjects (top 5 percentile triglyceride values, 100% initial participation, 6% drop out). The 150 healthy type IV subjects, ages 20 to 49, were randomly divided into treatment subgroups: A, treatment by clinic nutritionist and physician with the National Heart and Lung Institute's type IV diet for 6 weeks, then diet plus clofibrate for 18 weeks; B, same treatment by private physician; C, no intervention for 24 weeks, subjects advised of abnormality. The group A mean fasting serum triglyceride of 407 mg/dl declined 50% at 6 weeks, 61% at 12 weeks, and was unchanged at 24 weeks (P less than 0.0005 at 6, 12, 24 weeks). Group B triglyceride decreased 42%, 50%, 41% (P less than 0.0005 at 6, 12, 24 weeks). Group C triglyceride declined 20%, 1st to 24th week. Body weight decreased 8% (A) and 4% (B) at 6 weeks (P less than 0.0005) and was unchanged at 24 weeks. The maximum cholesterol decrease (A) was 11% (P less than 0.0005). Type IV hyperlipoproteinemia can readily be identified in a working population; treatment by clinic or private physician will markedly lower fasting serum triglyceride values in apparently healthy type IV subjects for at least 24 weeks.

Thirty-eight patients with diffuse glomerulonephritis of systemic lupus erythematosus were randomly assigned to add cyclophosphamide, azathioprine, or nothing to low-dose corticosteroid treatment and have been followed for a mean of 21/3 years thereafter. Of the 11 patients with unfavorable outcomes (8 deaths and 2 beginning hemodialyses), 2 occurred on cyclophosphamide, 4 on azathioprine, and 5 on prednisone only. Deaths due to infection occurred on the cytotoxics, while deaths ascribed to central nervous system lupus erythematosus occurred exclusively on prednisone only. Gradual deterioration of renal function was observed in all three groups, most frequently on prednisone only. Undesirable events, some due to drugs, were observed. At the time of reporting, the cytotoxic agents seemed to add marginally to the control of the disease; other treatment schedules should be evaluated.

A prospective, randomized drug trial compared prednisone (60 mg per day initially) to azathioprine (3 to 4 mg/kg of body weight - day initially) plus prednisone in 24 patients with life-threatening systemic lupus erythematosus. Each group contained patients matched for age, sex, disease duration, previous therapy, and clinical and laboratory features of lupus erythematosus. During a mean follow-up period of 18 to 24 months, there were no significant differences between the two groups in number of deaths, renal or extrarenal manifestations of disease, serum complement levels, DNA antibodies, antinuclear antibody titers, lupus erythematosus cells, or Coombs' antibodies. There was no convincing evidence of a steroid-sparing effect of azathioprine. Side effects attributable to steroids were equally common in both groups; infections were not increased in the combination therapy group. Azathioprine was hepatotoxic in doses of 200 mg daily or more. Azathioprine was not a useful adjunct to corticosterolds in short-term therapy of a small number of patients with severe systemic lupus.

Ten patients with the Pickwickian syndrome, characterized by obesity, hypoxemia, hypercapnia, polycythemia, and cor pulmonale, underwent long-term treatment as outpatients with medroxyprogesterone acetate. Although there was no significant weight change in the group, PaO2 rose 12.6 +/- 2.7 mm Hg (SEM) from 49 +/- 2.6 mm Hg to 62 +/- 2.3 mm Hg (P less than 0.001), while PaCO2 fell 13 +/- 2.6 mm Hg from 51 +/- 1.9 mm Hg to 38 +/- 1.2 mm Hg (P less than 0.001). Hematocrit fell from 56 +/- 2.5% to 50 +/- 1.2%, a mean fall of 6% (P less than 0.01), during medroxyprogesterone acetate therapy. In the 2 patients who had cardiac catheterization before and during medroxyprogesterone acetate therapy, mean pulmonary arterial pressure fell 13 and 19 mm Hg. There were no recurrences of cor pulmonale during treatment. These effects on arterial blood gas values and clinical state were sustained during therapy. On withdrawal of medroxyprogesterone acetate during 1-month period, arterial oxygen and carbon dioxide tensions deteriorated to their previous pretreatment values. Reinstitution of medroxyprogesterone acetate caused improvement in both the oxygen and carbon dioxide tensions. We conclude that sublingual medroxyprogesterone acetate therapy is useful in the management of the Pickwickian syndrome.

The effects of oral propranolol and digoxin and digoxin alone and in combination on angina frequency, heart size, systolic time intervals and treadmill exercise tolerance, were assessed in 20 patients with coronary heart disease. Oral propranolol alone reduced the average frequency of angina pectoris from 16 to 7 attacks per week (P less than 0.02). However, the mean duration of exercise was not significantly improved because 8 patients with abnormal left ventricular function exhibited a decrease in exercise tolerance. Combined propranolol and digoxin improved exercise tolerance in these patients, and, consequently, mean exercise duration in all patients increased significantly from the control value of 390 +/- 42 to 458 +/- 46 s (P less than 0.01). Propranolol alone also resulted in a significant increase in left heart size from 46.5 +/- 1.3 to 47.7 +/- 1.5 mm/m2 (P less than 0.001), which was reversed by the addition of digoxin. Therefore, oral propranolol combined with digoxin is advantageous in patients with angina pectoris who have abnormal ventricular function or large hearts.

To evaluate the interaction between the antibiotic rifampin and the anticoagulant warfarin during chronic therapy, eight normal subjects were given daily doses of warfarin for 21 days to achieve therapeutic hypoprothrombinemia. Daily blood samples were analyzed for one-stage prothrombin activity and for warfarin content spectrophotometrically and chromatographically. One month later, the same warfarin dose was repeated plus rifampin, 600 mg a day orally. For the last 10 days of every experiment, there was a highly significant lessening of both the hypoprothrombinemic effect (P less than 0.001) and the blood levels of warfarin (P less than 0.001). No significant difference in the warfarin levels was found between the spectrophotometric and chromatographic methods. It is concluded that rifampin markedly decreases the hypoprothrombinemic effect of warfarin during long-term therapy by enhancing its elimination from plasma. This conclusion was reinforced by finding increased amounts of warfarin metabolites in urine and stool.

The effect of breathing 100 ppm of carbon monoxide versus compressed, purified air for 1 h on maximal treadmill exericse was studied (double-blind crossover design) in 10 middle-aged, healthy nonsmokers. The mean venous carboxyhemoglobin level significantly increased from 1.67% to 3.95% after breathing carbon monoxide (P less than 0.001) and significantly decreased from 1.63% to 1.30% after breathing compressed, purified air (P less than 0.001). The mean exercise time until exhaustion significantly decreased from 697.7 to 662.7 s after breathing carbon monoxide (P less than 0.001) and insignificantly increased from 694.9 s to 703.4 s after breathing compressed, purified air. Ischemic S-T segment depression larger than or equal to 1.0 mm after exercise occurred in 1 of 10 subjects after exercise following carbon monoxide inhalation. Increased carboxyhemoglobin levels of the magnitude encountered after smoking or heavy atmospheric pollution impair exercise performance in normal persons.

Amikacin (BB-K8) is a semisynthetic derivative of kanamycin which is active in vitro against many gentamicin-resistant Gram-negative bacilli. Twenty-three patients with 25 serious Gram-negative infections were treated with this new aminoglycoside. Twelve infections involved organisms that were resistant to gentamicin. Twenty patients satisfied the criteria for bacteriological and clinical cure. This included 11 of the 12 infections involving gentamicin-resistant Gram-negative bacilli. In 4 urinary tract infections there was a good clinical response, but routine follow-up urine cultures at 30 days were positive. One patient failed on amikacin therapy. Eighth nerve toxicity was detected in two patients. These results indicate that amikacin is effective in the treatment of serious Gram-negative infections and is particularly useful in those involving resistant organisms. Further studies are indicated to evaluate ototoxic potential.

The efficacy of naproxen in treating rheumatoid arthritis patients was evaluated in a double-blind clinical trial using aspirin as the control drug. The study was conducted at seven centers and involved 80 patients. After an unequivocal increase in disease activity during a drug-free period, patients were randomly assigned to either drug and continued in the trial for 16 weeks. Some patients took low maintenance doses of corticosteroids, or gold salts, or both throughout the trial. Both test drugs significantly decreased disease activity as measured by a number of ways. By objective measurements, naproxen was as effective as aspirin, although patients in the naproxen-treated group entered the trial with more severe disease. By some subjective evaluations, naproxen was considered more effective than aspirin. Although patients taking naproxen had less frequent gastrointestinal side effects and fewer symptoms VIIIth nerve toxicity, the differences were not statistically significant. We conclude that naproxen is a useful addition to the physician's armamentarium for the treatment of rheumatoid arthritis.

We studied 18 patients with moderate to severe asthma for cardiac response to repeated doses of isoproterenol aerosol. In only 1 patient was there a significant increase in heart rate immediately after inhalation of isoproterenol aerosol, and it lasted only for 1 minute. In 2 patients increased heart rate was either due to breathholding or to the propellant in the aerosol. There was no cumulative effect on heart rate. Arrhythmias did not develop at any time despite repeated doses of aerosol every 5 to 20 minutes. Peak expiratory flow rate increased 5 minutes after the first dose, and it increased even further after repeated doses; at no time did it decrease after repeated doses.