Gerald W. Keusch

Sodium-volume factor, cardiovascular reactivity and hypotensive mechanism of diuretic therapy in mild hypertension associated with diabetes mellitus☆

Abstract Diabetes mellitus is often associated with excess body sodium and frequently accompanied by hypertension. Relationships among blood pressure and various regulatory factors were studied before and after six weeks of diuretic therapy with chlorthalidone, 100 mg/day, in 17 diabetic subjects (aged 32 to 75 years) with borderline to moderate hypertension. Following a four-week placebo phase, mean supine blood pressure was 165/93 ± 26/15 (±SD) mm Hg and exchangeable sodium was increased (49 ± 4 versus 45 ± 4 meq/kg lean body mass in 90 normal subjects; p

IgA nephropathy and hypercalcemia in Whipple's disease

In 2 patients an IgA nephropathy was found 2 and 5 years before gastrointestinal symptoms led to the diagnosis of Whipples disease. One patient additionally presented with hypercalcemia. Subsequently 1 patient died, whereas treatment with trimethoprim/sulfamethoxazole resulted in an improvement of IgA nephropathy and in a complete recovery from hypercalcemia and all the manifestations of Whipples disease in the other patient. IgA nephropathy and hypercalcemia may be considered as early manifestations of Whipples disease.

Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation.

Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (< 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by auto-antibodies to erythroblasts, this type of PRCA could be viewed as “heteroimmune disease.”

Peritonitis During Continuous Ambulatory Peritoneal Dialysis: Improving Patient Defense by Type of Buffer of Dialysate?

Replication of Staphylococcus aureus as well as phagocytosis by normal human leucocytes was studied in acetate and lactate containing dialysate in vitro. Bacterial replication was neither impaired nor promoted by the media tested. Phagocytosis occurred at the same rate in both solutions studied.

Evidence for a beneficial effect of plasma exchange in severe active lupus nephritis

Abstract We examined the impact of plasma exchange (PE) on the long-term course of active lupus nephritis in 7 female patients (age 21–48 yr, mean 32). Before starting PE all patients had renal failure (serum creatinine 347 ± 194 μmol L ) proteinuria (6.2 ± 3.4 g/24 h) and hematuria. Renal biopsies performed before PE in 5 cases showed a membranoproliferative glomerulonephritis in 3 cases, a moderate focal and segmental glomerulonephritis in one case, and a diffuse proliferative glomerulonephritis in one case. All specimens showed active lesions. PE was carried out with the Haemonetic Model 50 blood cell separator. The volume of plasma removed (2.3–4 L per run) was replaced by human plasma-protein fraction (PPL, SRK-Hu-man). 7–135 runs (mean 36) were performed over a period of 13–1619 days (mean 359). At the time of PE all patients received prednisone in combination with azathioprine or cyclophosphamid. The course of renal failure was analyzed by plotting the reciprocal values of the serum creatinine vs time. The mean period of analysis before and after initiation of PE was 15.8 and 30.3 months, respectively. Before PE renal function was deteriorating rapidly in all 7 patients. After PE renal function improved in 3 patients, stabilized in 1 patient and deteriorated at a slower rate compared to the pre-treatment period in 2 patients. No beneficial effect of PE on renal function was observed in 1 patient. We conclude that PE combined with immunosuppressive drugs may have a favorable impact on the long time-course of lupus nephritis.

200. Die subtotale Parathyreoidektomie zur Behandlung des tertiären Hyperparathyreoidismus

SummaryIn some patients with chronic renal failure, persistent hypocalcemia may develop due to secondary hyperparathyroidism; the term “tertiary hyperparathyroidism” is used for such cases. In a four-year period, parathyroidectomy was performed in 22 patients. The operation procedure was to remove three of the glands, and from the fourth so much tissue that the remainder was half the size of a rice grain; this was marked with a silver clip. The serum calcium dropped from 2.79±0.25 to 1.9±0.48 mmol/1. Extra osseous calcification disappeared within months. We conclude that subtotal parathyroidectomy is a safe and effective procedure in tertiary hyperparathyroidism. We emphasize that the size of the remaining gland or tissue must not be more than half a grain of rice.ZusammenfassungAls tertiärer Hyperparathyreoidismus versteht man die Hypercalciämie aufgrund eines entgleisten sekundären Hyperparathyreoidismus. In einem Zeitraum von vier Jahren haben wir 22 Patienten operiert. Wir entfernen drei Epithelkörperchen und soviel des vierten, daß nur noch Gewebe in der Größe eines halben Reiskornes zurückbleibt. Die Lage wird mit einem Silberklips markiert. Dadurch fiel das Serumcalcium von 2,79±0,25 auf 1,9±0,48 mmol/l. Extraossäre Verkalkungen verschwanden im späteren Verlauf. Die subtotale Parathyreoidektomie hat sich als Therapie des tertiären Hyperparathyreoidismus bewährt. Ausschlaggebend ist, daß nur ein Restepithelörperchen von der Größe eines halben Reiskornes zurückbleibt.

Circulating immune complexes before and after kidney allotransplantation

In a prospective study circulating immune complexes (CIC) were analyzed before and serially after renal transplantation in 141 consecutive patients. CIC were measured using the Raji cell assay as originally described by Theofilopoulos and Dixon. The amount of CIC was expressed as microgram heat aggregated human immunoglobulin G (IgG) equivalent/ml serum. The upper limit of normal sera was 25 micrograms/ml. The values are expressed as geometric means (- 1 SD/ + 1 SD). In 86 of 133 rejection episodes a renal biopsy was performed and the histopathologic changes were semiquantitatively assessed and classified in a cellular or vascular type of rejection. Before transplantation CIC were detected in 104 of 141 patients (73.8%) and the mean value was 65.6 (27.8-154.9) micrograms/ml. The level of CIC was positively correlated with the number of grafts (r: 0.43; P less than 0.01) and the occurrence of chronic active hepatitis (r: 0.31; P less than 0.01). No correlation was found between CIC and the underlying kidney disease, the number of blood transfusions prior to transplantation, and the pre-existing lymphocytotoxic antibodies. Graft survival and number of rejection episodes were not influenced by the level of CIC prior to transplantation. After transplantation CIC were elevated in 60 patients (41%), appeared transiently in 49 patients (35%) and were never detectable in 32 patients (23%). In patients with a graft survival less than or equal to 11 months the average and peak post-transplant CIC levels were significantly higher than patients with a graft survival of 12 months: 64.4 (21.8-191.0); 87.7 (26.0-295.8) versus 39.6 (18.4-85.3); 56.8 (21.0-150.1) micrograms/ml; P less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)SummaryIn a prospective study circulating immune complexes (CIC) were analyzed before and serially after renal transplantation in 141 consecutive patients. CIC were measured using the Raji cell assay as originally described by Theofilopoulos and Dixon. The amount of CIC was expressed as µg heat aggregated human immunoglobulin G (IgG) equivalent/ml serum. The upper limit of normal sera was 25 µg/ml. The values are expressed as geometric means (−1 SD/+1 SD). In 86 of 133 rejection episodes a renal biopsy was performed and the histopathologic changes were semiquantitatively assessed and classified in a cellular or vascular type of rejection. Before transplantation CIC were detected in 104 of 141 patients (73.8%) and the mean value was 65.6 (27.8–154.9) µg/ml. The level of CIC was positively correlated with the number of grafts (r:0.43;P<0.01) and the occurrence of chronic active hepatitis (r:0.31;P<0.01). No correlation was found between CIC and the underlying kidney disease, the number of blood transfusions prior to transplantation, and the pre-existing lymphocytotoxic antibodies. Graft survival and number of rejection episodes were not influenced by the level of CIC prior to transplantation. After transplantation CIC were elevated in 60 patients (41%), appeared transiently in 49 patients (35%) and were never detectable in 32 patients (23%). In patients with a graft survival ≦11 months the average and peak post-transplant CIC levels were significantly higher than patients with a graft survival of 12 months: 64.4 (21.8–191.0); 87.7 (26.0–295.8) versus 39.6 (18.4–85.3); 56.8 (21.0–150.1) µg/ml;P<0.01. There was a positive correlation between CIC and serum creatinine in the post-transplant period (P<0.001). The histopathologic severity and morphological type of rejection did not correlate with CIC. In patients without rejection episodes CIC were significantly lower: 41.2 (39.6–42.9) than patients with rejection episodes: 61.8 (56.2–68.0);P<0.05.