Biomedical subjects
Publications and source records attributed to G Schrijver.
We described two elderly patients with severe hyponatremia that was probably caused by inappropriate secretion of antidiuretic hormone. The hyponatremia arose during fluoxetine (Prozac) antidepressant therapy.
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We describe 2 case reports dealing with accidental hypothermia in which continuous veno-venous haemofiltration and dialysis (CVVHD) in combination with hyperinfusion with heated crystalloids was used as a rewarming technique. In this way it also is possible to correct metabolic disturbances, even during cardiopulmonary resuscitation.
Cyclosporin A (CsA) can reduce proteinuria in various forms of human and experimental glomerulonephritis. This antiproteinuric effect of CsA may be the consequence of diminution of immunological damage, a drug-induced decrease of GFR, or changes in permselectivity of the glomerular basement membrane (GBM). We studied the antiproteinuric effect of CsA in the heterologous phase of a passively induced anti-GBM nephritis in the mouse. This passive model is characterized by acute exudative glomerular lesions and a dose-dependent albuminuria. Rabbit anti-mouse GBM antibodies were administered intravenously in C57B110 mice at day 4, after 3 days of pretreatment with either CsA (75 mg/kg body weight) (n = 15) or olive oil (OO, controls, n = 15) orally. CsA did not influence the severity of the histological lesions. Albuminuria was substantially reduced by CsA (CsA 1.6 +/- 1.8; OO 5.6 +/- 3.2 mg/18 h; P < 0.002). There was a considerable concomitant reduction of the GFR by CsA, as measured with a 51Cr-EDTA single-shot plasma clearance technique before (day-1) and during treatment (day 4): GFR ratio day 4/day-1 for CsA, 0.4 +/- 0.1; for OO controls, 1.1 +/- 0.6; P < 0.01. This drug-induced decrease of GFR was prevented by simultaneous treatment with phenoxybenzamine (PB) twice daily 45 micrograms orally for 4 days (GFR ratio day 4/day-1 for PB and CsA, 0.9 +/- 0.4; controls (PB and OO), 1.0 +/- 0.4; P = NS). Although the CsA-induced GFR reduction was prevented, CsA still reduced albuminuria significantly (PB and CsA, 2.2 +/- 1.8; controls (PB and OO), 5.6 +/- 1.8 mg/18 h; P = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
In a 78-year-old female with hyponatraemia, the syndrome of inappropriate ADH secretion as a side effect of fluoxetine, a relatively new antidepressive drug, was tentatively diagnosed. In the literature 14 cases of this adverse reaction have been described. One should be careful when prescribing fluoxetine to elderly persons, notably when a diuretic is prescribed as well.
A patient is described with Sjögren's syndrome and an IgM-kappa gammopathy. With time cryoglobulins, the cause of acute renal failure, could be detected. The kidney biopsy showed a proliferative glomerulonephritis as is frequently seen with mixed cryoglobulinaemia. Plasmapheresis and immunosuppression resulted in long-term improvement of kidney function. The differential diagnosis of acute renal failure of glomerular origin in a patient with Sjögren's syndrome is discussed. This case report illustrates once more the consequences of monoclonal B-cell lymphocyte activation in Sjögren's syndrome.
The role of polymorphonuclear granulocytes (PMNs) was studied in a model of anti-GBM nephritis in mice, in which PMN depletion was induced by total body irradiation of 7.5 Gy. Both in complement-normal B10.D2 new and in C5-deficient B10.D2 old mice, PMN depletion completely prevented the albuminuria occurring after injection of low doses of anti-GBM serum, and severely depressed the albuminuria after injection of high doses. In immunofluorescence, glomerular deposition of antibody and C3 was similar to that in control mice. The glomerular influx of PMNs in both the complement-normal and C5-deficient controls was inhibited to 10% or less of control values. Fibrin deposition or necrosis did not occur. Injection of F(ab')2 fragments of the anti-GBM antibody in non-irradiated mice caused only limited PMN influx and reduced the albuminuria to physiological levels, although the binding of 125I labeled F(ab')2 fragments to the glomeruli was as high as 82% of that of the complete antibody. We conclude that the albuminuria in this model is Fc-dependent and largely, if not completely, dependent on the influx of PMNs in the glomeruli. Among the many experimental models of anti-GBM nephritis, this is the first one in which the heterologous phase is complement-independent but PMN-dependent.
Antiglomerular basement membrane (GBM) nephritis with massive albuminuria can be induced in mice by injection of heterologous antibodies against mouse GBM. The albuminuria and the glomerular lesions in this model are not mediated by complement, but are dependent on the presence of polymorphonuclear granulocytes (PMN) in the glomeruli. Neutral serine proteinases and reactive oxygen metabolites produced by activated PMN have been implicated as agents contributing to tissue damage. We examined the role of leukocytic neutral proteinases by comparing the glomerular damage and albuminuria after injection of rabbit anti-mouse GBM antibodies in normal control mice (C57BL/6J, +/+) and in beige mice (C57BL/6J,bg/bg) in which PMN are deficient of the neutral proteinases elastase and cathepsin G. The dose-dependent albuminuria that occurred in control mice after injection of 1.4-22 mg of anti-GBM antibodies was not observed in beige mice, despite a comparable influx of PMNs in the glomeruli. By electron microscopy both strains showed a similar attachment of PMN to the denuded GBM together with swelling and necrosis of endothelial cells. Elastase activity of extracts from PMN of beige mice was only 10-15% of the activity of control mice. In vitro, GBM degradation by PMN extracts of beige mice was 70% lower than that seen in control experiments. PMNs of beige and control mice showed no differences in superoxide production. In addition, administration of scavengers of reactive oxygen metabolites, such as catalase and desferrioxamine, did not prevent the albuminuria in this model. These findings support the important contribution of leukocytic neutral proteinases to the induction of albuminuria in the acute phase of anti-GBM nephritis in the mouse.
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A simple and fast hemolytic microassay was developed for the determination of classical pathway complement activity in mouse serum. The assay is based on hemolysis of sheep red blood cells (SRBC) that are sensitized with polyclonal mouse antibodies. The degree of hemolysis was measured in the reaction supernatants by photometric reading in an ELISA plate scanner at 405 nm wavelength. It was found that some batches of unpurified mouse anti-SRBC antibodies gave insufficient hemolysis. Analysis of two antibody preparations indicated that this might be caused by anti-complementary factors in the ascites fluid, and by an excess of non-complement fixing IgG1 antibodies. For optimal and standardized results, removal of anticomplementary factors and enrichment for complement fixing IgG2 antibodies was required and was achieved using protein A purified anti-SRBC IgG. In our assay it is possible to determine CH50 titers in triplicate in 80 microliters samples of individual mouse sera with high sensitivity. Using this rapid one-step method large numbers of tests could be performed in 1 day.
The role of complement was examined in a model of antiglomerular basement membrane nephritis in the mouse, induced by intravenous injection of goat anti-mouse glomerular basement membrane serum, and characterized by early glomerular lesions and a dose-dependent albuminuria. We compared the reaction after injection of the antiserum in complement-normal B10.D2 new mice with that in congenic, congenitally C5-deficient B10.D2 old mice, and in both strains after C3 depletion by treatment with cobra venom factor. The dose-dependent albuminuria was not affected by the absence of complement activation. Also, deficiency of C3 and/or C5 had no inhibitory effect on the histologic glomerular lesions: it did not reduce the influx of polymorphonuclear granulocytes in the glomerular capillary vessels, nor prevented the eventual intravascular coagulation. We conclude that complement-independent mechanisms are involved in the development of the heterologous phase of antiglomerular basement membrane nephritis in the mouse.
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Highly reproducible anti glomerular basement membrane (GBM) nephritis has been induced in the mouse after a single injection of rabbit or goat antibody against purified homologous GBM. The severity of albuminuria was closely related to the amount of antibody given. With doses of 4 mg or more, low serum albumin concentrations, sometimes accompanied by ascites and oedema, were observed after 1 week. Glomerular injury was characterized by an initial accumulation of polymorphonuclear granulocytes followed by thrombosis and necrosis, the extent of which defined the outcome of the glomerulonephritis. With high doses of antibody the exudative lesions entered a chronic phase, while at doses lower than 2 mg remission of the lesions occurred. Immunofluorescence studies showed prompt linear fixation of the injected antibodies to the glomerular capillary wall, accompanied by immediate binding of C3 in a fine granular pattern. Fibrin deposits appeared at 2 h in some glomeruli, increased thereafter, and were present after one day in more than 90% of the glomeruli in mice that had received 4 mg of antibody. This new reproducible model in the mouse is suited for the study of the relationship between activation of mediator systems, histological lesions, and proteinuria.
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A double-blind study of hydrochlorothiazide and spironolactone, alone and in combination, was conducted in 49 patients with mild-to-moderate essential hypertension after a 4-wk placebo washout period. In the whole group mean arterial blood pressure fell to levels of less than or equal to 107 mm Hg or declined by more than 15 mm Hg in 78% of the patients after twelve weeks of treatment. Sixty-nine percent of patients receiving hydrochlorothiazide alone developed serum potassium levels lower than 3.5 mEq/L; serum potassium levels were above 5.5 mEq/L in 2 patients (5.5%) receiving spironolactone 400 mg/day. Uric acid levels rose in all patients, more in those on hydrochlorothiazide, but clinical gout did not develop in any subject. Hydrochlorothiazide, spironolactone, and the combination of the two are effective antihypertensives. Spironolactone in doses of 200 and 400 mg/day was associated with side effects but did not induce a greater antihypertensive effect than doses of 100 mg/day. Our data suggest that when hydrochlorothiazide is associated with potassium loss, when gout or elevated uric acid levels are of concern, or when carbohydrate tolerance is abnormal, supplementation or replacement with spironolactone (up to 100 mg/day) may be useful in controlling blood pressure while reducing side effects.
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