Francis X. Schloeder

Bolivian hemorrhagic fever: A report of four cases

Abstract Four cases of epidemic hemorrhagic fever, which occurred among members of a team investigating the disease in Bolivia, are described. The similarity in the epidemiology, clinical course and causative agent of this disease to Argentine hemorrhagic fever is noted. Speculations about the pathophysiology of this disease, which appears to be similar to Korean hemorrhagic fever, and a review of the current concepts of therapy are presented.

Antiglobulins and glomerulonephritis. Classification of patients by the reactivity of their sera and renal tissue with aggregated and native human IgG.

Renal biopsies and sera from 41 consecutive patients were studied to determine if antiglobulins were found more frequently in patients with severely diseased glomeruli. Patients were classified into three groups: A, 12 patients with normal renal function and minimal histological evidence of glomerular disease; B, 18 patients with normal renal function but distinctly abnormal biopsies (16 cases) or proteinuria greater than 16 g/24 h (2 cases); and C, 11 patients with both decreased function and abnormal histology. Positive latex fixation tests for rheumatoid factor were found in none of group A, four (22%) of group B, and five (45%) of group C patients. Sera heated 56 degrees C for 30 min contained precipitins reactive with heat-aggregated IgG in none of seven group A, five of ten (50%) group B, and four of ten (40%) group C patients. The quantity of 135I-labeled patient globulin which bound to immunoadsorbents coated with Cohn fraction II in competition with an equal quantity of 131I-labeled globulin from pooled plasma of normal donors was also measured. Patient globulins bound in significantly greater quantity (greater than or equal 2 SD) than the control in none of the group A, 7 of 18 (39%) group B, and 7 of 11 (64%) group C patients. Renal biopsies from 18 patients were also studied for the ability to fix fluorescein-conjugated heat-aggregated and native human IgG. None of nine tissue specimens from group A or B patients fixed either fluorescein-conjugated protein whereas tissue from eight of nine group C patients showed glomerular localization of one or both reagents. Severity of disease as judged by renal function and glomerular histology correlated with the presence of tissue-fixed and serum antiglobulins. Thus, detection of antiglobulins in glomeruli and sera of patients with glomerulonephritis may indicate a relatively poor prognosis and raises the possibility that antiglobulins may be implicated in some way in the pathophysiology of human glomerulonephritis.

Clinical studyBolivian hemorrhagic fever: A report of four cases

Abstract Four cases of epidemic hemorrhagic fever, which occurred among members of a team investigating the disease in Bolivia, are described. The similarity in the epidemiology, clinical course and causative agent of this disease to Argentine hemorrhagic fever is noted. Speculations about the pathophysiology of this disease, which appears to be similar to Korean hemorrhagic fever, and a review of the current concepts of therapy are presented.

Defect of urinary acidification during fasting.

Abstract The capacity of the kidney to secrete hydrogen ions against a gradient was evaluated during fasting. Six healthy obese individuals were subjected to the short ammonium chloride loading test before and after 8 days of fasting. Fasting was continued for an additional 5 days, during which each subject was given 300 mEq. of potassium chloride. After the potassium replacement, a third ammonium chloride loading test was performed. The results demonstrated that after 8 days of fasting the renal capacity to depress the urine pH after ammonium chloride loading was completely lost, but that this impairment was reversed by the administration of potassium chloride.

Studies on the natriuresis of fasting: II. Relationship to acidosis☆

Abstract The relationship of acidosis to the natriuresis of fasting was investigated by producing a metabolic acidosis in the prefast period with ammonium chloride. The results show that as a result of this exogenous acidosis, the natriuresis of fasting was considerably reduced. It was concluded that the greatest part of the sodium excretion due to fasting is lost during adaptation to the metabolic acidosis which occurs, and that this can be markedly reduced by adaptation to acidosis in the prefast period.

Studies on the natriuresis of fasting: I. Effect of prefast intake☆

Abstract By employing low sodium diets in the prefast period, the effects of salt restriction and fasting were temporarily separated so that the character and magnitude of the natriuresis due to caloric withdrawal could be determined. During fasting, there was a rise in the mean sodium excretion beginning on the second day, reaching a peak on the fourth day, and subsiding thereafter. It is concluded that the natriuresis attributed to fasting in previous studies consisted of 2 separate but concurrent processes: (1) an early and rapidly diminishing sodium loss due to withdrawal from salt, and (2) a pattern of sodium excretion similar to that described above. The mechanisms and origins of the sodium lost as a result of fasting are considered, and it is suggested that both extracellular and intracellular spaces play varying roles as fasting progresses.

The effect of age on the character of immune complex disease: a comparison of the incidence and relative size of materials reactive with Clq in sera of patients with glomerulonephritis and cancer.

The impact of aging on the severity of chronic immune-complex glomerulonephritis was studied in 144 patients from whom diagnostic renal biopsies were obtained over a 3-year period. Glomerulonephritis was related to an antecedent streptococcal infection in nine of these patients. In 58, glomerulonephritis occurred in association with a systemic disease; 27 of these had lupus erythematosus. At the time of the renal biopsy, serum creatinines were more frequently abnormal in men over 40 years of age. Similarly, histological evidence of irreversible glomerular injury was more evident in men over 40. Histological indices of renal glomerular injury correlated with the presence of intense fluorescent antibody reactions specific for C3 and C4 and IgG in the glomeruli. High serum Clq binding activities (Clq BA), an indication of the presence of circulating immune complexes, also were found significantly more often in males over 40. High serum Clq BA correlated with renal functional and biopsy evidence of severe glomerulonephritis. The renal biopsies in 89 cases were tested with fluorescein-conjugated heat-aggregated IgG (FAIgG) to determine how many contained focal immunoglobulin deposits with antiglobulin activity. Antiglobulins were detected in glomeruli of 24 patients and were found significantly more often in biopsies which revealed histological evidence of severe and irreversible histological injury. Binding of FAIgG was not selectively associated with any sex or age groups. Thus, detection of circulating immune complex-like materials in sera and the presence of glomerular deposits with antiglobulin activity were both features associated with severe glomerular injury. Both correlated with the quantity of complement deposited in the glomeruli. But only serum Clq binding activity was age and sex related. Similarly, in cancer patients, abnormal Clq BA were found more frequently in sera of older men with cancer but not in age- and sex-matched controls. Examination of selected sera by sucrose density gradient ultracentrifugation revealed that the complexes from cancer patients were relatively small (less than 19S greater than 7S) whereas those in most nephritis patients were heterogeneous in size. Sera with relatively high Clq binding activity from patients with chronic glomerulonephritis tended to contain relatively greater quantities of Clq binding materials sedimenting more rapidly than 19S.

Glucose-induced alkalosis in fasting subjects: Relationship to renal bicarbonate reabsorption during fasting and refeeding

This study documents the development of alkalosis in patients returning to caloric intake after a period of starvation and investigates the mechanisms responsible for this metabolic alteration. We studied the acid-base status, bicarbonate reabsorption, acid excretion, and sodium metabolism during fasting and glucose refeeding in 19 patients receiving sodium supplements. Metabolic alkalosis developed promptly in all of the subjects who terminated an 18 day fast with 300 g of glucose daily for 4 days. Tubular maximum reabsorptive capacity for bicarbonate and renal bicarbonate threshold determinations were performed at varying intervals in six and seven subjects, respectively, who had fasted for 3-18 days. The results demonstrated that bicarbonate reabsorptive capacity was normal or low during early fasting, markedly elevated during the 2nd wk; and moderately elevated during the 3rd wk of fasting. Glucose administration at all stages of fasting caused a further increase in bicarbonate threshold. Sodium balance during fasting with sodium supplements was found to follow a triphasic pattern, with the occurrence of a natriuresis during the 1st wk followed by a period of sodium retention after which neutral daily sodium balance was reestablished. Correlation of bicarbonate reabsorption with sodium homeostasis indicated a slight decrease in renal bicarbonate threshold during the natriuretic phase, a marked increase in bicarbonate reabsorption during the period of sodium retention, and a continued moderate elevation of threshold after sodium balance was reestablished. This relationship was interpreted to indicate that changes in bicarbonate reabsorption during fasting and refeeding may be secondary to alterations in the renal reabsorption of sodium.

Renal Tubular Sites of Natriuresis of Fasting and Glucose-induced Sodium Conservation

Abstract The sites in the nephron involved in the natriuresis of fasting and its reversal by glucose have been investigated. Alterations in urinary volume (V), glomerular filtration rate (GFR) and free water clearance (CH2O) were studied during water diuresis prior to fasting, on the fifth fasting day and immediately after the administration of glucose. The results demonstrate that fasting is associated with an increase in V GFR and in C H 2 O GFR , but a decrease in the ratio C H 2 O V . Glucose promptly reverses these changes to values similar to the prefast state. It was concluded that both proximal and distal sites in the nephron are involved in the natriuresis of fasting and its reversal by glucose.

Disequilibrium pH and bicarbonate reabsorption: relevance to the pathogenesis of distal renal tubular acidosis.

An augmented renal capacity to reabsorb bicarbonate (RHCO3) has been noted in patients with distal renal tubular acidosis (dRTA), and construed as evidence that the basic defect in dRTA is abnormal distal tubular permeability. According to this interpretation, the absence of a disequilibrium pH due to a back-leak of H2C03 permits increased distal H+ secretion and results in an increased RHCO3. To test this assumption, we have evaluated the effect of acute elimination of the disequilibrium pH by carbonic anhydrase infusion. The results establish that this maneuver doses not cause a rise in RHCO3. Thus, the elevated value of RHC3 described in dRTA cannot be the consequence of increased back-diffusion of H2CO3 and is more likely due to coexisting extracellular volume depletion and/or postassium deficiency.