Altered membrane sodium transport in Bartter's syndrome.

To explore the possibility that Bartter's syndrome is the manifestation of an inherited abnormality of sodium transport, we have measured various parameters of sodium transport in erythrocytes from patients with Bartter's syndrome, their siblings, and their parents. Sodium transport in six of the eight patients with Bartter's syndrome differed significantly from that in the other two patients. On the basis of this difference, the patients were divided into two groups (type I and type II). In the six type I patients, fractional sodium outflux (0.38+/-0.05/hr [SD]) was significantly less than normal (0.50+/-0.07) and erythrocyte sodium concentration (9.48+/-0.84 mmoles/liter cells per hr) was significantly greater than normal (5.24+/-0.66). In the two type II patients, none of the measured parameters of sodium transport differed significantly from normal. Erythrocyte sodium transport in the relatives of three type I patients was altered in a way similar to that in the type I patients and was significantly different from that in the relatives of a type II patient. These findings indicate the presence of inherited alterations of erythrocyte sodium transport in certain patients with Bartter's syndrome.

Typhoid hepatitis with immunoglobulins and complement deposits in bile canaliculi.

Documented typhoid fever in a 26-year-old patient was complicated by acute hepatitis with unusually profound jaundice. Liver biopsy revealed focal cell necrosis, mononuclear cell infiltration. Kupffer cell proliferation, and mild cholestasis. Immunofluorescent studies of the liver biopsy revealed deposits of IgG, IgA, IgM, and C3 in the bile canaliculi, suggesting a role for damage by immune complexes in typhoid hepatitis.

Familial hyperpotassemia and hypertension accompanied by normal plasma aldosterone levels: possible hereditary cell membrane defect.

Hypertension and hyperpotassemia that were accompanied by normal plasma aldosterone and low renin levels and were responsive to chlorothiazide administration were found in a 29-year-old patient and two decades later in his 21-year-old son. Their renal function is normal, including response to sodium sulfate, mannitol, and aldosterone infusions. Adrenal insufficiency was excluded. The renin-aldosterone system was proved intact by physiological and pharmacologic stress and angiotensin-II infusion. Also normal were values for blood counts, blood volumes, and erythrocyte and exchangeable body potassium. The postulation of a defective cell membrane impeding potassium influx is supported by the failure of glucose and insulin infusions to substantially reduce hyperpotassemia. In the context of a hereditary disorder (the pedigree, compatible with autosomal dominant inheritance, includes five affected in two generations), hypertension is a second phenotypic character of a single defective pleiotropic gene although its pathogenesis remains unclear.

Controlled trial of propranolol in intermittent claudication.

Seven patients (5 with arteriosclerosis obliterans and 2 with Buerger's disease) completed a two-phase double-blind crossover trial of propranolol in intermittent claudication. Performance was measured on a moving treadmill. In the initial phase, the patients were hospitalized in order to determine an "effective" dose of propranolol. Improvement was noted in all: after 1,600 mg in 5 and after 240 mg and 600 mg in the others. The controlled phase was carried out on an outpatient basis over 8 weeks, the patients receiving propranolol and placebo in a random manner, each for two 2-week periods. Comparison of matched periods of drug and placebo revealed no advantage for propranolol. Patients' performances deteriorated with time. None of the patients evidenced deterioration of occlusive peripheral arterial disease that could be attributed to propranolol, in spite of the high doses used.

Increased 25-hydroxyvitamin D levels in portal blood following cholecystokinin injection in the dog.

To establish whether an enterohepatic circulation of the metabolites of vitamin D exists, polyethylene catheters were cannulated into the portal vein of dogs. The dogs were then starved for 24 h and injected with cholecystokinin (CCK) to induce gall bladder contraction. At various time intervals thereafter blood samples were collected from the portal and the saphena veins, and sera prepared and analyzed for the metabolites of vitamin D. The serum levels of 25-hydroxyvitamin D [25(OH)D] were found to be significantly higher in the portal blood when compared with levels in peripheral blood following CCK injection. Since portal blood collects nutrients absorbed from the gut and as the dogs were starved for 24 h prior to blood collection, the only source of the increased concentrations of 25(OH)D in portal blood is likely to be bile. These findings support the notion that an enterohepatic circulation of 25(OH)D does exist under normal physiological conditions.

Amyloidosis associated with renal cell carcinoma of the AA type.

Amyloid fibrils were found at postmortem examination in a 70 year old woman with generalized amyloidosis associated with renal carcinoma (hypernephroma). Clinically, her amyloid disease presented as nephrotic syndrome. It was demonstrated by electrophoretic and amino acid sequence analysis studies that the amyloid fibrils contained AA protein identical to that found in amyloidosis associated with chronic inflammatory and infectious diseases as well as in the genetic form of familial Mediterranean fever.

Restoration of in vitro hematopoiesis in B-chronic lymphocytic leukemia by antibodies to tumor necrosis factor.

Hematopoiesis was evaluated in 15 B-CLL patients using the mixed colony formation assay. The mean growth of all types of colonies in B-CLL peripheral blood was significantly lower than that of 10 normal controls (p less than 0.05). To investigate whether TNF is the cytokine involved in the reduced growth of hematopoietic progenitors in B-CLL, neutralizing anti-TNF antibodies (anti-TNF Abs) were added to the cultures. Anti-TNF Abs optimized in vitro hematopoiesis in 11 out of 15 B-CLL patients and a significant growth increase in all types of colonies was noted as compared to baseline cultures (p less than 0.05). In patients with stage IV disease, the increase in both mixed and erythroid colonies was more prominent than in patients with earlier disease stages. This optimization of growth was also observed in normal control cultures containing accessory cells. However, high TNF levels were measured in conditioned media from CLL patients and suppressed normal bone marrow hematopoietic progenitors growth. In contrast no TNF was detected in normal conditioned media. It is concluded that TNF and other cytokines, among them IL-3, play a role in the regulation of hematopoietic function in some B-CLL cases. These findings may have clinical applicability.

Recurrent miliary tuberculosis secondary to infected ventriculoatrial shunt.

The placing of a ventriculoatrial anastomosis because of elevated CSF pressure secondary to tuberculous meningitis resulted in repeated dissemination of Mycobacterium tuberculosis from the anastomosis. The consequent clinical picture showed recurrent appearance and clearing of miliary tuberculosis of the lung in spite of antituberculosis chemotherapy. While this possibility was considered early, the diagnosis was not established until the shunt was replaced shortly before the patient's death.

Multiple neuropathic arthropathy in a patient with syphilis.

An unusual case of neuropathic arthropathy in a patient with tabes dorsalis is presented. The special feature consisted of multiple joint involvement in the upper limbs and spine. This uncommon location of Charcot joints can probably be attributed to the patient's occupation which involved heavy strains on his upper limbs.

Heat stroke: a review.

Heat stroke is a complex clinical picture caused by extreme elevation of body temperature and is especially prevalent in hot climates. The danger of heat stroke has apparently always accompanied unacclimatized man on his way through arid zones, and was often the cause of man's fatal adventures in the desert. Large numbers of unacclimatized urban dwellers have suffered when the urban areas have been involved in heat waves. Heat stroke has also been a major problem in hot industrial environments. This paper is a review of pertinent literature on this subject.

Dynamic changes in acid base balance during heatstroke in dogs.

The dynamic changes in acid base balance and respiratory metabolism during the development of heatstroke in dogs were studied. Three groups of five unanesthetized dogs each were exposed to different climatic conditions while at rest: A) 24 degrees C, 50% relative humidity (RH); B) 35 degrees C, 35% RH, and C) 45 degrees C , 25% RH. These conditions were maintained for 4 h or until the dogs collapsed. The heatstroke dogs were cooled in tap water bathes and were observed for another 4 h. Dogs of groups A and B did not show any notable changes in rectal temperature (Tre) and acid base balance. All dogs in group C developed heatstroke. Their peak mean Tre (44.1 degrees C) was reached after a mean of 111 min of exposure, with respiratory alkalosis followed by increasingly severe metabolic acidosis above Tre of 42 degrees C. At peak Tre mean arterial pH was 7.26. Acidosis increased (pHa = 7.17) following cooling, as panting subsided. At Tre above 42 degrees C blood lactate increased and bicarbonate decreased significantly, attaining mean values of 58 mg% and 8 mEq/l, respectively. Bicarbonate changes correlated linearly with lactate changes. During recovery lactate decreased and blood pH increased approximating normal by the end of the experiment. The results illustrate the body's ability to spontaneously correct arterial pH without therapeutic means.

Recurrent septic arthritis due to Pseudomonas sp.

Two episodes of Pseudomonas septic arthritis occurred in an 84-year-old diabetic man separated by a 6 year interval. Pseudomonas is an unusual cause of septic arthritis requiring vigorous antibiotic therapy. The recurrence of the infection may be related to the inadequate response to treatment in the first episode, however, the long interval remains unexplained.