Short-term protein loading in assessment of patients with renal disease

The effect of short-term protein loading on the glomerular filtration rate in normal persons and patients with renal disease was evaluated. Previous studies have demonstrated that in healthy subjects, protein loading results in an increased glomerular filtration rate. By determining the glomerular filtration rate preceding (baseline glomerular filtration rate) and following (test glomerular filtration rate) oral protein loading, it was possible to define (1) the filtration capacity (test glomerular filtration rate) and (2) the renal reserve (test glomerular filtration rate - baseline glomerular filtration rate) of the kidney. In normal persons, filtration capacity averaged 157 +/- 13 ml per minute and renal reserve 34 ml per minute. The test glomerular filtration rate was reproducible and independent of protein intake, whereas baseline glomerular filtration rate was significantly influenced by diet. Patients with renal disease were found to have a reduced renal reserve and/or a diminished filtration capacity. The reduction in filtration capacity appears to correlate with the damage sustained by the organ. It is suggested that an abnormal response to protein loading in renal disease may herald the fall in the baseline glomerular filtration rate and the rise in plasma creatinine level.     

Failure of mean red cell volume to serve as a biologic marker for alcoholism in narcotic dependence. A randomized control trial

Mean red cell volume, mean red cell hemoglobin, and mean red cell hemoglobin concentration were measured in a prospective, longitudinal, single-bind study of alcoholism and its treatment in 625 patients receiving methadone. Mean red cell volume and mean red cell hemoglobin were significantly elevated in alcoholic as compared with nonalcoholic patients (p less than 0.001), with a sensitivity of 40 and 51 percent, respectively. The ability of an elevated mean red cell volume and mean red cell hemoglobin to exclude active alcoholism (specificity) was 86 and 76 percent, respectively. Development of excessive consumption of alcohol during the course of the study was not associated with significant elevations over baseline values of either mean red cell volume or mean red cell hemoglobin. Similarly, the mean red cell volume and mean red cell hemoglobin in the small number of patients whose consumption of alcohol markedly decreased did not significantly change from baseline values. These findings suggest that although the specificity of mean red cell volume may be helpful in eliminating those persons who are not actively alcoholic, its sensitivity does not permit its use as a biologic marker for alcoholism. The inclusion of an elevated mean red cell volume as a major criterion for the diagnosis of alcoholism should be reconsidered.     

Renal function in gout. V. Factors influencing the renal hemodynamics

Renal hemodynamics as measured by inulin clearance (Cinulin) and para-aminohippurate clearance (CPAH) was evaluated in 149 patients with primary gout over intervals of two to 22 years. In over 30 per cent of the patients plasma urate was greater than 10 mg/dl and urinary uric acid greater than 800 mg/min. A linear trend in decreasing frequency of hyperuricemia and excessive uricosuria is significantly related to the patient's age at the onset of gout. Group I consisted of 84 patients with uncomplicated gout in both clearance studies. Cinulin and CPAH were somewhat lower in patients larger than or equal to 50 years of age with longer duration of gout. Further reduction in clearances was minimal at the second clearance study in intervals of approximately 10 years. Group II included 27 patients who had no associated disease at the time of the first clearance study but in whom associated disease had developed by the time of the second clearance study. A striking reduction in Cinulin and CPAH was noted, especially in those 50 years old or above. There were 38 patients in group III with associated diseases at the time of both clearance studies. They had lower Cinulin and CPAH at the time of the first study, particularly the older patients. Further reduction during the second study was less striking than that in group II. Analyses of variance suggest that various coexisting vascular diseases with associated nephropathy have the most significant impact on the status of renal function in gout, with aging the second most important and duration of gout, the third.     

Alcoholism as a risk factor in methadone maintenance: A randomized controlled trial

A randomized controlled trial of 625 addicts on methadone maintenance identified 105 (17 percent) as active alcoholics, 47 (8 percent) as inactive alcoholics, and 473 (75 percent) as nonalcoholics. Subjects were followed for up to 29 months (mean 53.7 weeks) to assess the influence of alcoholism on the rehabilitative process. During the study, alcohol consumption significantly decreased (p < 0.001) in active alcoholics. Indexes of productive activity on entry or during follow-up revealed no significant differences between active alcoholics and other patients with the exception of alcohol-related hospitalizations (p < 0.001). Behavioral indexes consistently improved with treatment in all patients, being greatest among active alcoholics (p < 0.01). During the study, 28 (7 percent) of 399 nonalcoholics were recategorized as active alcoholics, and remission from alcoholism was noted in 28 (27 percent) of patients who were initially classified as alcoholic. These findings suggest that alcoholism does not significantly affect rehabilitation from narcotic use and therefore should not be cause for detoxification from methadone maintenance.     

Clotrimazole treatment of oral candidiasis in patients with neoplastic disease

A double-blind controlled study was performed to evaluate the effectiveness of Clotrimazole in the treatment of oral candidiasis in patients with neoplastic disease. Six of seven patients who received clotrimazole had resolution of symptoms and signs of oral candidiasis. In five of six patients who received placebo, clinical progression of signs and symptoms occurred, esophagitis developed, and amphotericin B therapy had to be given. No toxicity was observed that could be attributed to clotrimazole. The results were statistically significant (p = 0.025 by Fisher's exact test). Clotrimazole is effective therapy for oral candidiasis in patients with neoplastic disease, and may prevent the development of esophagitis.     

Immune thrombocytopenia and Gaucher's disease

A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.     

Malignancy in primary biliary cirrhosis. High incidence of breast cancer in affected women

Primary biliary cirrhosis is characterized by abnormalities in both cellular and humoral immunity. It is associated with presumably autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis, and scleroderma. Sjögren's syndrome and scleroderma have been noted to have an increased frequency of malignancy. Of 208 patients with primary biliary cirrhosis, followed for one month to 15.9 years, extrahepatic malignancies developed in 11, six of whom were women with breast cancer, and one with hepatocellular carcinoma. The incidence of breast cancer was 4.4 times (p < 0.01) the incidence expected from the rate prevailing in the same age range in a comparable normal population. The incidence of cancer in sites other than the breast and of primary hepatocellular tumor was not significantly increased.     

Intraleukocytic sequestration as a cause of persistent Staphylococcus aureus peritonitis in continuous ambulatory peritoneal dialysis

Peritonitis caused by Staphylococcus aureus in four patients undergoing continuous ambulatory peritoneal dialysis failed to respond to, or relapsed immediately after cessation of, intraperitoneal antibiotic therapy with vancomycin or cephalothin and tobramycin. Sequestration of viable staphylococci within polymorphonuclear leukocytes in the peritoneal fluid was suspected for two reasons: (1) staphylococci could still be grown after treatment of the dialysate cell fraction with lysostaphin, a procedure that kills only extracellular staphylococci, and (2) diminished polymorphonuclear leukocyte bactericidal activity was demonstrated in peritoneal dialysis effluent. Addition of rifampin, which readily penetrates polymorphonuclear leukocytes, to the treatment regimen of all patients led to prompt resolution of peritonitis without relapse.     

Long-term follow-up of incorporation of 15N from glycine into uric acid in gout

The incorporation of ¹⁵N-glycine into urinary uric acid was studied in three gouty patients, repeating a study carried out 13 to 27 years ago. The ¹⁵N incorporation attained a lower maximum and declined less rapidly in the repeat study in all three patients. The cumulative ¹⁵N incorporation into uric acid was reduced to one half of that determined previously. Similarly, urinary uric acid excretion was less, along with a lower uric acid nitrogen to total nitrogen ratio. The data indicate changes in the nature of the metabolic aberrations, which are apparently related to long-term drug therapy, changes in lifestyle, aging and associated medical complications.     

Solitary pulmonary nodules due to nontuberculous mycobacterial infection

Resected solitary pulmonary nodules which histologically are granulomas and in which acid-fast bacilli are seen are usually assumed to be due to infection with Mycobacterium tuberculosis. We reviewed the culture results of all resected lung specimens submitted to the mycobacteriology laboratory from 1969 to 1979. Of the 20 specimens in which acid-fast bacilli were seen and which roentgenographically were solitary pulmonary nodules, 12 (60 percent) were due to infection with M. avium-intracellulare. In five granulomas, acid-fast bacilli were seen but failed to grow on culture. In one instance each, M. tuberculosis, M. fortuitum and M. gordonae grow on culture. Fiberoptic bronchoscopy was not diagnostic in 10 patients, although in one patient M. avium-intracellulare was cultured from the bronchial washings. Lymph nodes removed at mediastinoscopy from 12 patients did not contain granulomas. Since the physician was often unaware that cultures subsequently grew nontuberculous mycobacteria, most patients were treated with two drug regimens for presumed tuberculosis. Postoperative follow-up was available for 14 of the 20 patients, for a period ranging from four months to 10 years. There was no instance of dissemination of the infection to lung or pleura. We conclude that solitary pulmonary “tuberculomas” are often due to nontuberculous mycobacterial infection, particularly M. avium-intracellulare. When the lesion is due to nontuberculous mycobacteria and can be resected in its entirety, drug therapy is not indicated.     

Carotid sinus hypersensitivity. Case report and review of the literature

Carotid sinus hypersensitivity is a potentially treatable cause of recurrent neurologic symptoms. Diagnosis depends upon recognizing the variable presentation of symptomatic carotid sinus hypersensitivity, and noting an exaggerated cardiovascular response to carotid sinus massage associated with neurologic symptoms. Once the diagnosis of symptomatic carotid sinus hypersensitivity has been established, it is important to delineate the type of hypersensitivity present, because identification of the vasodepressor response has important therapeutic implications.     

Fatal disseminated adenovirus 11 pneumonia in an agammaglobulinemic patient

Adenovirus type 11, an organism not previously associated with pneumonia, caused the death of a patient with infantile x-linked agammaglobulinemia who had normal cell-mediated immunity. Despite long-standing, regular therapy with immune globulin, his serum lacked neutralizing antibody to the virus. This case confronts the conventional view that viral infections are primarily resisted by cellular immune reactions and reemphasizes the importance of antibody in the host defense against adenoviruses. It further demonstrates the continued vulnerability of such patients to certain pathogens in the presence of presumably adequate standard-dose passive immunization.     

Normolipemic subcutaneous xanthomatosis

A patient with diabetes mellitus is described in whom an unusual xanthomatosis developed involving large areas of the subcutaneous tissue and vocal cords. Few lesions were present on the skin. Plasma lipid, lipoprotein, apolipoprotein, and cholestanol levels revealed normal patterns. Electron microscopy showed macrophages with vacuolar and crystal lipid inclusions. Results of lipid and enzyme analysis of the subcutaneous xanthoma were similar to those of xanthomas derived from a patient with diabetes mellitus and type V hyperlipidemia. The mechanism of this xanthomatosis remains unknown.     

Impaired renal function in gout: Its association with hypertensive vascular disease and intrinsic renal disease

Inulin clearance was measured in 624 patients with gout, and para-aminohippuric acid (PAH) clearance in 359; Group I consisted of 397 patients with uncomplicated gout; Group II, 191 patients with hypertension and/or ischemic heart disease; and Group III, 36 patients with chronic renal disease. Mean inulin clearance was normal in Group I, slightly depressed in Group II and more markedly decreased in Group III. There was some reduction in PAH clearance in all groups, but not in the very young patients with no complications. A disproportionate reduction in PAH clearance was noted in Groups II and III, particularly in the older patients with longer duration of gout. Uncomplicated gout, except in rare cases of fulminating gout, does not lead to decreased renal hemodynamics. An increased incidence of tophi correlates with decreased renal function, but incidence of renal calculi does not. Renal insufficiency when seen in patients with gout usually correlates with coexistence of hypertension, ischemic heart disease, or primary preexistent renal insufficiency.     

Randomized versus historical controls for clinical trials

To compare the use of randomized controls (RCTs) and historical controls (HCTs) for clinical trials, we searched the literature for therapies studied by both methods. We found six therapies for which 50 RCTs and 56 HCTs were reported. Forty-four of 56 HCTs (79 percent) found the therapy better than the control regimen, but only 10 of 50 RCTs (20 percent) agreed. For each therapy, the treated patients in RCTs and HCTs had similar outcomes. The difference between RCTs and HCTs of the same therapy was largely due to differences in outcome for the control groups, with the HCT control patients generally doing worse than the RCT control groups. Adjustment of the outcomes of the HCTs for prognostic factors, when possible, did not appreciably change the results. The data suggest that biases in patient selection may irretrievably weight the outcome of HCTs in favor of new therapies. RCTs may miss clinically important benefits because of inadequate attention to sample size. The predictive value of each might be improved by reconsidering the use of p < 0.05 as the significance level for all types of clinical trials, and by the use of confidence intervals around estimates of treatment effects.     

Ventilatory failure due to asbestos pleurisy

Seven patients are described who had a distinctive syndrome of chest wall restriction caused by asbestos-induced pleural fibrosis. All had severe dyspnea and predominant pleural disease on radiographic examination, with pulmonary function findings of reduced vital capacity, total lung capacity (measured in five patients), and maximal voluntary ventilation. Five patients had ventilatory failure with carbon dioxide retention; four of these have died and one is close to death. Examination of the thoracic organs in five patients showed minimal or no parenchymal fibrosis in three and less severe involvement of the parenchyma than of the pleura in the remaining two. Neoplasms were suspected in three patients because of extension of the pleural fibrosis into the lung. Two of these patients had pleural uptake of 67-gallium citrate attributable to the inflammatory reaction. With the increasing duration since onset of exposure in the nine million workers who have been exposed to asbestos, as well as in other exposed persons, it is expected that additional cases of ventilatory failure caused by asbestos-induced pleural fibrosis will be encountered.