Treatment of recurrent idiopathic nephrotic syndrome after transplantation using plasmaphaeresis and intensified immunosuppression over 2 months.
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Adolescent↗
Biomedical subjects
A Zimmermann
Publications and source records attributed to A Zimmermann.
Increased bone metabolism in a patient undergoing long-term rhG-CSF treatment for idiopathic acquired neutropenia.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used mainly for treatment of chemotherapy-induced neutropenia. The reported side effects were of minor importance. We describe a case of long-term treatment with rhG-CSF, in which we observed enhanced bone remodeling.
Adult↗
Lymphocyte subpopulations in healthy newborn infants: comparison of cord blood values with values five days after birth.
Significant differences (p < 0.0001) were demonstrated in lymphocyte subpopulations both in cord blood and in venous blood samples obtained at day 5 from the same healthy infants. Numbers of T lymphocytes increased, especially CD4+/CD45RA+ cells, whereas numbers of B lymphocytes and natural killer cells decreased without changes in CD8+ and other cytotoxic cells.
Female↗
Biliary retention in a chronic choledocho-venous fistula in the rat: induction of portal hypertension but not of biliary cirrhosis.
In this study we investigated whether the retention of compounds which are excreted into the bile could contribute to portal hypertension in secondary biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13 of the animals had biochemical evidence of partial obstruction. Microsomal function, as measured by the aminopyrine breath test, was decreased in all animals with biliary retention while microsomal cytochrome P-450 content was decreased only in rats with evidence of obstruction. All animals with biliary retention with or without partial obstruction had portal hypertension. Animals with biliary retention and partial obstruction had hypercholeresis but decreased bile salt excretion. All animals with a chronic catheter in the biliary tree had a loss of the negative permselectivity of the sinusoidal-canalicular barrier and decreased maximal bile secretory pressure. Only animals with biochemical evidence of obstruction had moderate fibrosis and ductular proliferation as determined by stereological techniques. Unexpectedly, morphometric analysis also revealed an increase in hepatocyte mass induced by biliary retention. We conclude that bile contains a compound(s) which induces portal hypertension. This putative substance is neither bilirubin nor a bile acid since portal hypertension was also observed in animals with biliary retention without obstructive signs.
Aminopyrine↗
Acute effects of partial hepatectomy on liver blood flow in the jaundiced rat.
The aim of this study was to define the effects of hepatic resection on liver blood flow and portal pressure in the presence of obstructive jaundice. Liver blood flow and portal pressure were measured in 17 jaundiced animals (5 days bile duct ligation) and 16 control animals. A 70% liver resection with or without hepatic artery ligation was performed in the control animals. On day 5, the animals underwent a second operation. Hepatic artery ligation alone was performed in a group of control animals. In jaundiced rats there was a decrease in liver blood flow (1.24 +/- 0.23 ml/min per g vs. normal 1.91 +/- 0.38 ml/min per g, P < 0.01) and an increase in portal pressure (11.2 +/- 3.47 mmHg vs. normal 6.93 +/- 1.01 mmHg, P < 0.01). After partial hepatectomy, a significant increase in liver blood flow was observed in controls (2.44 +/- 0.74 ml/min per g, P < 0.01) but not in jaundiced rats. Hepatic artery ligation did not affect blood flow or portal pressure either before or after resection. Small but significant portal-systemic shunting was found in all jaundiced rats (2.19 +/- 2.1% vs. 0.026 +/- 0.015%, P < 0.05). These results demonstrate that partial hepatectomy results in a significant increase in total liver blood flow. Acute cholestasis appears to prevent this increase. Even in the early stages of obstructive jaundice in the rat, there were signs of portal-systemic shunts.
Animals↗
Effect of orthotopic transplantation and chemical denervation of the liver on hepatic hemodynamics in the rat.
The involvement of the sympathetic nervous system in the control of basal hepatic hemodynamics was investigated. Hepatic denervation was achieved by orthotopic transplantation or chemical denervation of the organ. In male Lewis rats, transplantation with rearterialization of the graft was performed. Chemical denervation was achieved by intraportal injection of 6-hydroxydopamine (75 mg/kg). Normal liver physiology was confirmed by histology and liver function tests. Four weeks post-transplantation and 7 days post-denervation, histological examination revealed no differences between transplanted, denervated and untreated or sham-operated control animals. Liver function measured by standard tests (e.g., plasma SGOT, bilirubin) was normal in all groups. The rate constants for aminopyrine breakdown in transplanted (0.015 +/- 0.005 min-1), denervated (0.015 +/- 0.0012 min-1) and control rats (0.015 +/- 0.001 min-1) were not significantly different. No significant difference in the rate of galactose breakdown was found. Total liver blood flow (measured by the 133Xe clearance technique in the anesthetized animal) was unaffected by transplantation (rate constant, 0.245 +/- 0.062 min-1; control 0.279 +/- 0.011 min-1). The interlobular distribution of portal blood flow was tested by intraportal injection of 51Cr-labelled microspheres. A linear relationship between flow to lobe and lobe size was confirmed in control (r = 0.95), denervated, (r = 0.99) and transplanted rats (r = 0.97) and the 'relative' flow to each lobe was not significantly different in the 3 groups. No significant differences in the 'core' to 'periphery' distribution of portal blood flow were found in the 3 groups. A small but significant portal systemic shunt was found in transplanted but not denervated or control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate.
Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma-glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue.
Adult↗
HPLC is an effective and fast method for analysis of viral proteins: a study of encephalomyocarditis virus mutants differing in pathogenicity.
We investigated the use of HPLC in analysis of picornavirus variants by comparing structural polypeptides of three stable mutants of encephalomyocarditis virus (EMCV). The variants are known to differ in their pathogenicity for mice: plaque variant 2 (PV2) is diabetogenic, PV7 is non-diabetogenic and PV21 induces a generalized lethal infection. We first used HPLC to separate the structural proteins at high purity levels. Detailed analysis of these structural proteins by HPLC-peptide mapping revealed differences in all four viral proteins of PV21 as compared with mutants PV2 and PV7. A single amino acid exchange was found in viral protein 1 between PV2 and PV7. Altered peaks were identified by calculating retention times of tryptic peptides using sequence data and a computer program. Since peak alterations could be attributed to the observed amino acid exchanges, the results correlate well with cDNA sequencing data. Thus HPLC proved to be a useful and fast tool for primary or additional characterization of picornavirus variants at the level of whole virus proteins.
Capsid↗
Vertical LM sectioning and parallel CT scanning designs for stereology: application to human lung.
Practical, unbiased stereological methods are described to estimate lung volume and external surface area, and total volume and surface area of relatively large and anisotropic structures (bronchi and arteries) inside the lung. The volume of each of five lung strata was estimated first by fluid displacement and then by computed tomography (CT) using Cavalieri's method; the reliability of CT was assessed through a calibration procedure, and image thresholding criteria for an accurate volume estimation using CT were established. The parallel, perfectly registered CT section images were also used to estimate the external surface area of each stratum by the spatial grid method. Unbiased estimation of internal surface areas in lung is a long-standing problem: since the structures are large and essentially void, large sections are needed; to facilitate identification, thin sections have to be used for light microscopy, and since such structures are anisotropic, the sections should be vertical. A practical stereological design is demonstrated here on an infant lung, which fulfils all these requirements. This study illustrates the potential of using unbiased stereology to characterize infant pulmonary hypoplasia.
Female↗
Gingivitis, plaque accumulation and plaque composition under long-term use of Meridol.
The effectiveness of amine fluoride and stannous fluoride in the prophylaxis of caries and gingivitis is well-known from the literature. The aim of this study was to assess whether these agents could be recommended for long-term use. Under conditions of a clinical double-blind study, the influence of an amine/stannous fluoride rinse on gingivitis, plaque accumulation and the composition of the supragingival plaque was tested over a period of 7 months. 102 persons with signs of chronic gingivitis participated in the study. Gingival indices (GI, SBI) and plaque indices (PlI, API) were recorded at baseline, after 3.5 and 7 months. The composition of the supragingival plaque was evaluated by dark-field microscopy. During the 7 months, the GI decreased in the test group from 1.36 to 0.95, and the SBI from 52.0% to 29.3%. The PlI fell from 1.17 to 0.68, and the API from 61.3% to 50.6% (p < 0.001). No significant changes were recorded in the control group. In the test group, the proportion of cocci in the plaque increased from 58.4% to 68.9% (p < 0.001) while the proportion of rods and other plaque bacteria underwent a significant decrease (p < 0.001). The microflora was stable in the control group throughout the study period. No side-effects of the drug were reported by the probands. The results suggest that long-term use of the amine/stannous fluoride rinse is of benefit to gingival health.
Adolescent↗
Treatment of refractory ulcerative oesophagitis with omeprazole.
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Esophagitis↗
Proliferation of guinea pig tracheal epithelial cells induced by calcitonin gene-related peptide.
Calcitonin gene-related peptide (CGRP) is contained within and secreted by nerves and neuroepithelial bodies in the airway epithelium. To determine whether CGRP is mitogenic for airway epithelial cells, tracheal epithelial cells isolated from 26 guinea pigs were grown in primary culture for 2 days. Subconfluent cells were exposed to 10(-13) to 10(-9) M CGRP for 4 h and then returned to CGRP-free medium. Proliferation was quantified by direct cell count and by measurement of fractional labeling with the thymidine analog, bromodeoxyuridine (BrdU). CGRP exposure increased both cell number (53,980 +/- 9,870 cells after 10(-9) M CGRP versus 33,910 +/- 5,150 cells after control, P < 0.05) and fractional BrdU labeling (12.9 +/- 2.2% after 10(-11) M CGRP versus 3.9 +/- 0.9%, control; P < 0.01, n = 9) at 24 h after exposure. The mitogenic effect of CGRP persisted at least 3 days after exposure. CGRP-induced proliferation was attenuated by co-incubation with the CGRP receptor antagonist, hCGRP-(8-37). These data demonstrate that CGRP causes proliferation of guinea pig tracheal epithelial cells in primary culture through stimulation of a specific receptor, and suggest a role for this neuropeptide in regulating airway epithelial cell growth.
Animals↗
Increased plasma viscosity as a reason for inappropriate erythropoietin formation.
The aim of this study was to examine whether altered plasma viscosity could contribute to the inappropriately low production rate of erythropoietin (EPO) observed in patients suffering from hypergammaglobulinemias associated with multiple myeloma or Waldenström's disease. We found that the EPO formation in response to anemia in these patients was inversely related to plasma viscosity. A similar inverse relationship between plasma viscosity and EPO production was seen in rats in which EPO formation had been stimulated by exchange transfusion and the plasma viscosity of which was thereby altered by using exchange solutions of different composition to alter plasma viscosity and thus whole blood viscosity independently from hematocrit. Raising the gammaglobulin concentration to approximately 40 mg/ml plasma in the rats almost totally blunted the rise in serum EPO levels despite a fall of the hematocrit to 20%. Determination of renal EPO mRNA levels by RNase protection revealed that the reductions in serum EPO levels at higher plasma viscosities were paralleled by reductions in renal EPO mRNA levels. Taken together, our findings suggest that plasma viscosity may be a significant inhibitory modulator of anemia-induced EPO formation. The increased plasma viscosity in patients with hypergammaglobulinemias may therefore contribute to the inappropriate EPO production, which is a major reason for the anemia developing in these patients.
Adult↗
T cell receptor V beta gene bias in rheumatoid arthritis.
Polymerase chain reaction (PCR) technology was employed to examine peripheral blood and synovial T cells in patients with rheumatoid arthritis (RA) for biased utilization of T cell receptor (TCR) variable region (V) genes. Oligonucleotide primers specific for individual TCR V beta gene families were used to amplify TCR gene products in a semiquantitative assay of their relative utilization in unselected T cell populations. Mean V beta expression in 24 RA peripheral blood samples was very similar to that in a panel of 15 normal subjects, except for a slight decrease in V beta 13.2 expression. V beta utilization in 8 RA synovial tissue samples and 13 synovial fluid samples was compared to simultaneously obtained blood samples. Although heterogeneous patterns of skewed V beta utilization were observed, several significant trends emerged. By a number of approaches to data analysis, a statistically significant increase in expression of V beta 6 and V beta 15 in synovial T cells was documented. In addition, increased synovial expression of V beta 14 was found, but only in the synovial fluid samples. Reduced expression of V beta 1, V beta 4, V beta 5.1, V beta 10, V beta 16, and V beta 19 was also observed in synovial T cells. These results indicate that biased V beta gene utilization in different peripheral compartments of RA patients can be observed in unselected T cell populations, and are consistent with the conclusion that populations of T cells expressing these V beta gene products may be involved in the pathogenesis of the disease.
Adult↗
Increased benzodiazepine-like activity is neither necessary nor sufficient to explain acute hepatic encephalopathy in the thioacetamide-treated rat.
Increased levels of natural benzodiazepine receptor agonists, produced in the body (endogenous) or ingested with food (exogenous) have been proposed as one of the factors causing hepatic encephalopathy in both experimental animals and human subjects. However, the divergent response of hepatic encephalopathy to benzodiazepine antagonists sheds doubt on this attractive hypothesis. Acute liver failure was induced in male Sprague-Dawley rats (n = 17) with intraperitoneal thioacetamide (600 mg/kg/day for 3 days) while 14 control rats received vehicle only. Acute liver failure developed in all treated rats (AST: 1,898 +/- 1,359 IU/L vs. controls, 45 +/- 5 IU/L, p < 0.005; bilirubin: 36 +/- 27 mumol/L vs. controls, 1.5 +/- 0.5 mumol/L, p < 0.005; centrizonal necrosis) and grade 3 or 4 hepatic encephalopathy (neurologic assessment and activity monitoring). However, benzodiazepine receptor ligand activity, measured in the supernatant of whole-brain homogenates with a [3H]flumazenil binding competition assay, was clearly increased in only 1 of 17 rats with acute liver failure compared with controls (52.7 +/- 34.1 vs. 44.3 +/- 18.9 ng diazepam equivalents/gm; NS). To evaluate whether the reported increase in benzodiazepine receptor ligand activity could be due to prolonged residence of exogenous benzodiazepine-like substances, additional rats with acute liver failure and controls were treated with diazepam (five doses of 0.5 mg/kg at 12-hr intervals by gavage). Benzodiazepine receptor ligand activity was greater in animals with acute liver failure than in controls (223 +/- 65 vs. 103 +/- 23 ng diazepam equivalents/gm; p < 0.002) 1 to 3 hr after the last diazepam dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
"Neuroendocrine" differentiation in hepatocellular carcinomas (HCCs): immunohistochemical reactivity is related to distinct tumor cell types, but not to tumor grade.
We have analyzed neuroendocrine differentiation (ND) in hepatocellular carcinomas (HCCs) of fifty patients. It turned out that ND is frequent in HCCs, and that it is not restricted to fibrolamellar hepatocellular carcinoma (FL-HCC). Multiexpression is seen in a quarter of the cases, and marker coexpression may occur within the same tumor cell. ND predominates in trabecular and mixed HCCs, but does not appear to be related to grade. Most positive cases showed a hepatocyte-like cell morphology, frequently associated with bile formation. It thus appears that the HCC cell type most likely to show ND is a hepatocyte-like one, i.e. differentiated cell, frequently polarized and producing bile, rather than a small and poorly-differentiated cell. Possible pathogenic mechanisms leading to ND in HCCs are briefly discussed.
Adult↗
Morphometry of the liver after liver transplantation in the rat: significance of an intact arterial supply.
Two models of orthotopic liver transplantation in the rat currently used are with and without reconstruction of the hepatic artery. The aim of this study was to assess the importance of the arterial blood supply to liver structure after orthotopic liver transplantation with advanced morphometric methods. Orthotopic liver transplantation was performed in male Lewis rats, of which 11 underwent reconstruction of the hepatic artery and 11 did not. A group of untreated controls (n = 5) and a group of animals with hepatic artery ligation (n = 4) were included. Eight weeks after surgery liver tissue was harvested and subjected to systematic random sampling. A point-counting method was used, volume fractions of tissue components were determined. Liver samples from rats that underwent hepatic artery reconstruction had preserved lobular architecture, and estimated bile duct (0.71% +/- 0.33% [S.D.]) and connective tissue (1.89% +/- 0.52%) volumes were not significantly different from those of controls (bile duct, 0.34% +/- 0.17%; connective tissue, 0.70% +/- 0.07%). In contrast, liver samples from rats that did not undergo hepatic artery reconstruction showed bile duct proliferation (7.19% +/- 4.83%; p < 0.05) and an increase in connective tissue volume (7.54% +/- 3.68%; p < 0.05) associated with a decrease in hepatocyte volume (controls, 87.3% +/- 0.3%; rats that underwent arterialization, 85.5% +/- 1.0%; rats that did not undergo arterialization, 73.2% +/- 8.2% [p < 0.05]). Interestingly, hepatic artery ligation had no significant effect on any parameter.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[Glomerulonephritis with transient C3 hypoclompimentemia and endotheliomesangial glomerulonephritis in childhood. A long-term experience].
62 children (20 girls and 42 boys, ranging in age between 3 and 15 years), presenting with acute hypocomplementemic glomerulonephritis or morphologically confirmed endotheliomesangial glomerulonephritis, were admitted to the University Children's Hospital, Berne from 1970 to 1991. The annual incidence of cases of acute hypocomplementemic glomerulonephritis was stable during the study period. The site of the antecedent infection was the throat in 26 patients, upper respiratory tract in 15, the skin in 9, and unknown in 10. The latent period ranged from 0.5 to 3.5 weeks. 41 patients developed hypertension and 17 renal failure. Hypertensive complications were observed in 6 patients and remitted completely in 5 cases. A nephrotic syndrome (edema, proteinuria of 40 mg/[m2.h], albuminemia < 25 g/l) was observed in 11 patients. Microscopic hematuria persisted in many patients for one year or more. Proteinuria remitted in all but one patient, who was found to have Alport syndrome. This study shows the stable frequency of hypocomplementemic glomerulonephritis since 1970, its good prognosis, and the importance of the measurement of C3-complementemia in children presenting with acute glomerulonephritis.
Adolescent↗