Biomedical subjects
Publications and source records attributed to K Lhotta.
We herein present the first case in the literature of enucleation of an aldosterone-producing adenoma by laparoscopy. The indication for adrenal-sparing surgery was bilateral adrenal adenoma. The operation turned out to be easier than laparoscopic adrenalectomy. The postoperative course was uneventful, and the patient was cured; split adrenal function tests showed normal function of both adrenal glands.
A soluble form of intercellular adhesion molecule-1 (sICAM-1) has been described in serum and other body fluids. In order to determine whether sICAM-1 in serum and urine is a useful marker of inflammatory activity in kidney diseases we measured sICAM-1 in serum and urine of fifty patients who underwent renal biopsy, and of twenty healthy individuals. Expression of ICAM-1 on proximal tubular epithelial cells was investigated by immunohistochemistry. Soluble ICAM-1 in serum did not differ between patients and controls (354 +/- 129 ng/ml vs. 305 +/- 52 ng/ml). By multiple regression analysis sICAM-1 correlated with tubular expression of ICAM-1 (p < 0.01), but not with serum creatinine, infiltrating leukocytes, urinary ICAM-1 or proteinuria. In healthy controls mean urinary ICAM-1/cr was 2.5 +/- 3.0 ng/mg creatinine and differed significantly from that of patients (14.5 +/- 14.9 ng/mg) (p < 0.005). Patients with minimal-change disease had the highest uICAM-1 levels. The ratio of urinary ICAM-1 and proteinuria was remarkably constant in all patients with 6.0 +/- 0.9 ng/mg. By multiple regression analysis uICAM-1/cr correlated with proteinuria/cr (p < 0.001) and sICAM-1 (p < 0.005). These data show that sICAM-1 does to some degree reflect ICAM-1 expression in the kidney, whereas uICAM-1 is derived from glomerular filtration and closely parallels proteinuria. Both sICAM-1 and uICAM-1 are not useful to estimate ICAM-1 expression and inflammatory activity in the kidney.
A 10-year-old boy suffered from recurrent attacks of fever, vomiting, and hematuria. During disease flares, circulating immune complexes were detected in the serum. Elevated levels of Bb, Ba, and C3a indicated complement activation through the alternative pathway. Complement C4 was undetectable. C4 phenotyping by agarose gel electrophoresis showed complete C4 deficiency. Restriction fragment length polymorphism (RFLP) studies showed a homozygous deletion of the C4B and 21-hydroxylase A genes. A mild mesangioproliferative glomerulonephritis with mesangial deposits of immunoglobulin (1g) G, IgM, IgA, Clq, C3, properdin, and terminal complement complex was probably caused by immune complex deposition and alternative complement pathway activation. Treatment with low-dose prednisolone substantially reduced the frequency of further episodes.
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The phenotypes of complement C4 were determined by agarose gel electrophoresis in 130 patients with end-stage renal failure of various causes and compared with those of 140 healthy controls. C4 allotype frequencies did not differ between patients and controls. Null alleles of both isotypes C4A and C4B were increased, but also without reaching significance. In type 1 diabetics an increased frequency of C4AQ0 (25 vs. 11.8%, p < 0.05) was found. Patients with two null alleles were far more frequent in the group with insulin-dependent diabetes mellitus (25 vs. 3.6%, p < 0.01). We confirmed the presence of a previously described uremic variant of C4B1. Additional uremic variants of C4 were detected in uremic patients homozygous for C4A3, B2 and B3. The relative electrophoretic migration values of the uremic variants of C4A3, B1, B2 and B3 were 132.1 +/- 2.9, 35.8 +/- 1.5, 70.4 and 73.9. These variants appear early in the course of chronic renal failure and disappear after successful renal transplantation. Uremic variants are the only acquired C4 phenotypes known so far. How uremia causes these variants remains unclear, but probably involves carbamylation of the C4 molecule.
OBJECTIVE: The aim of this study was to investigate whether or not the inherited polymorphism of complement C4 is associated with genetic susceptibility to microvascular complications in IDDM as previously reported. RESEARCH DESIGN AND METHODS: We determined C4 phenotypes in 241 patients with IDDM and 140 healthy control subjects by agarose gel electrophoresis and immunoprecipitation. C4 allotype frequencies were compared between patients and healthy control subjects. In addition, we compared allotype frequencies of 83 patients with nephropathy with those of 80 patients without nephropathy and compared those of 50 patients with proliferative retinopathy with those of 68 patients without retinopathy or background retinopathy. Duration of IDDM in control patients was at least 21 years. RESULTS: Patients and healthy control subjects differed at both the C4A (P < 0.00001) and C4B (P < 0.0005) loci. The C4 null allele C4AQ0 was significantly increased in IDDM patients (26.8 vs. 11.8%, P < 0.005). C4B2 was more frequently observed in patients (14.5 vs. 6.8%, P < 0.05) compared with healthy control subjects. No differences were observed in C4 allotype distribution between patients with and without nephropathy or retinopathy. CONCLUSIONS: These data confirm previous reports of an association between the C4 null allele C4AQ0 and IDDM. Our results do not support an association of the inherited polymorphism of complement C4 with genetic susceptibility to microvascular complications in patients with IDDM.
BACKGROUND: Complement C4 is a component of the classical complement pathway, which is a major mediator of inflammation in many forms of glomerulonephritis. The two isoforms of C4-C4A and C4B-differ in their physicochemical and functional properties. METHODS: The glomerular deposition of C4A and C4B was investigated in 39 cases of glomerulonephritis with classical pathway activation using isotype-specific monoclonal antibodies 99H7 (C4A) and 1288 (C4B) and indirect immunofluorescence. Complement C4 phenotypes of all patients were determined by agarose gel electrophoresis and immunoprecipitation. RESULTS: Three biopsies contained only the isotype C4B. C4 phenotyping revealed complete C4A deficiency in these three patients. Both isotypes C4A and C4B were detected in 36 biopsies. In 19 (53%) thereof staining for both isotypes was identical. In the remaining 17 (47%), staining intensity of C4A predominated over C4B. The distribution of these two staining patterns did not differ between membranous glomerulonephritis and lupus nephritis. They were also independent of C4A and C4B allotypes including the presence or absence of null alleles at either gene locus. In no case was C4B staining stronger than C4A staining. Serum creatinine and proteinuria did not differ between patients with identical and C4A-dominant C4 deposition. CONCLUSIONS: The most likely but still hypothetical explanation for predominance in glomerular deposition of C4A over C4B in many cases of immune complex-mediated glomerulonephritis is the greater affinity of C4A to protein-containing immune complexes as compared to C4B.
Hepatitis, A is usually a mild and self-limiting infection of the liver. Whereas the clinical course is usually benign in children, complications such as prolonged cholestasis and fulminant liver failure have been reported in adults. Acute functional renal failure is an uncommon event in the absence of fulminating liver disease. So far, only cases of acute hepatitis A with biopsy-proven interstitial renal disease or tubular necrosis have been reported [Geltner et al. 1992. Kramer et al. 1986]. We present the case of a 35-year-old, previously healthy male with non-fulminant cholestatic viral hepatitis A, who developed progressive oliguric renal failure requiring dialysis therapy. Kidney biopsy ruled out glomerular disease and tubular necrosis. In the absence of bleeding and other causes of fluid depletion this case may be another variant of hepatorenal syndrome whose etiopathogenesis is only poorly understood.
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Recent studies have indicated a beneficial effect of one particular low molecular weight heparin preparation (Fragmin) on lipid metabolism in patients on chronic hemodialysis as compared to unfractionated heparin. We conducted a prospective crossover study with paired comparison of two different anticoagulant agents to examine the effects of a recently released new low molecular weight heparin (Sandoparin) on lipid and lipoprotein parameters in 24 patients starting hemodialysis. During the first six months of observation patients received Sandoparin. Then patients were switched to unfractionated heparin and observed for further six months. After switching from Sandoparin to unfractionated heparin we observed significant decreases in total cholesterol (from 168.6 +/- 42.2 to 154.4 +/- 41.9 mg/dl, p < 0.02), LDL cholesterol (from 106.4 +/- 35.2 to 89.9 +/- 32.3 mg/dl, p < 0.005), triglycerides (from 148.7 +/- 85.0 to 121.4 +/- 88.8 mg/dl, p < 0.05) and apolipoprotein B (from 100.0 +/- 35.3 to 89.9 +/- 30.4 mg/dl, p < 0.05) and a significant increase in HDL cholesterol (from 32.8 +/- 12.5 to 37.7 +/- 17.5 mg/dl, p < 0.02). This is in contrast to earlier results and can possibly be explained by a higher percentage of fractions with high M(r) in the investigated Sandoparin, which results in a more pronounced depletion of lipoprotein lipase. Together with the enhanced hepatic clearance of lipoprotein lipase induced by low molecular weight heparins, this may decrease lipoprotein lipase activity with a subsequent increase in plasma triglycerides, total and LDL cholesterol. We conclude from our data that a general recommendation for clinical use of low molecular weight heparin in hemodialysis patients cannot be given.
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1. The genetic background of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis remains largely unknown. Recently a very high prevalence of medium and severe deficiency of alpha 1-antitrypsin was described in a small group of patients with Wegener's granulomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and alpha 1-antitrypsin is the main inhibitor of this enzyme. 2. alpha 1-Antitrypsin phenotypic polymorphism was determined by isoelectric focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyarteritis and one suffered from idiopathic rapidly progressive glomerulonephritis. 3. Two patients were homozygous PiZZ and three were heterozygous PiMZ. These phenotype frequencies differed significantly from expected values, assuming Hardy-Weinberg equilibrium (P < 0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P < 0.001). 4. Furthermore, the serum of 47 patients with severe alpha 1-antitrypsin deficiency (PiZZ) was tested for the presence of ANCA. All sera were negative for c-ANCA and p-ANCA. None of the patients showed clinical signs of systemic vasculitis. 5. In conclusion, these data indicate that alpha 1-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease.
High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. In the general population, Lp(a) levels are primarily determined by allelic variation at the apolipoprotein(a) [apo(a)] gene locus. Apo(a) isoforms of various sizes are associated with different Lp(a) concentrations. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by the size variation at the apo(a) gene locus. To further investigate the origin of the elevated Lp(a) plasma concentrations, we examined Lp(a) concentrations and apo(a) phenotypes in 154 ESRD patients undergoing renal transplantation. In a prospective longitudinal study we observed a rapid normalization of Lp(a) levels from an average concentration of 25.9 +/- 28.7 mg/dL before to 17.9 +/- 25.5 mg/dL 3 weeks after renal transplantation (P < .0001). Only patients with high-molecular-weight phenotypes had a significant decrease in Lp(a) plasma concentrations. This study demonstrates the nongenetic origin of elevated Lp(a) concentrations in ESRD patients, which is obviously caused by the disease. It further confirms a phenotype-associated elevation of Lp(a) concentrations in ESRD.
Several studies have demonstrated that atherosclerotic complications are the major cause of morbidity and mortality in hemodialysis patients. High lipoprotein(a) [Lp(a)] plasma concentrations are an independent risk factor for atherosclerosis. Patients with end-stage renal disease (ESRD) have elevated plasma concentrations of Lp(a), which are not explained by size variation at the apolipoprotein(a) [apo(a)] gene locus. The aim of our study was to investigate whether Lp(a) concentrations and/or apo(a) phenotypes are predictive of the degree of atherosclerosis in the extracranial carotid arteries in ESRD patients. Of 167 patients, 108 showed atherosclerotic plaques (65%). Univariate analysis showed that the plaque-affected group was significantly older and had a higher frequency of angina pectoris, previous myocardial infarction, or cerebrovascular accident. Furthermore, this group included significantly more patients with low-molecular-weight apo(a) isoforms (26.9% versus 8.5%, P < .005) and had significantly higher mean Lp(a) plasma concentrations (29.3 +/- 31.0 versus 19.7 +/- 25.7 mg/dL, P < .05). Lp(a) plasma concentration increased significantly with the number of affected arterial sites, from 19.7 mg/dL in patients without plaques to 40.1 mg/dL in patients with seven or eight affected sites. In patients with low-molecular-weight phenotypes, significantly more arterial sites were affected (3.62 versus 2.08, P < .001). Multivariate regression analysis showed that age, angina pectoris, and the apo(a) phenotype were the only significant predictors of the degree of atherosclerosis. We conclude that, besides age, the apo(a) phenotype is the best predictor of carotid atherosclerosis in ESRD patients and may be used for assessment of general atherosclerosis risk in this patient group.
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Described here is a family in which the father with partial C4 deficiency had Wegener's granulomatosis and a son with complete C4 deficiency presented with Henoch-Schönlein Purpura. The possible role of C4 deficiency in the pathogenesis of both vasculitic disorders is discussed.