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Biomedical subjects

R Waldherr

Publications and source records attributed to R Waldherr.

At least 55 records · Page 3Linked to original sources
PubMed1997

The clinical spectrum of shunt nephritis.

BACKGROUND: Shunt nephritis is an immune-complex-mediated glomerulonephritis (GN) associated with chronically infected ventriculoatrial shunts inserted for treatment of hydrocephalus. METHODS: Six patients aged 5-22 years with shunt nephritis are reported who have been observed between 1971 and 1994. The clinical course and long-term outcome are analysed in relation to the time of diagnosis and renal histopathology. RESULTS: The time of diagnosis of shunt nephritis ranged from 0.3 to 4.5 years after the last shunt operation. Diagnosis was delayed up to 1.5 years after the first clinical manifestations. All patients had signs of infection, i.e. recurrent fever, hepatosplenomegaly, anaemia, and cerebral symptoms. Renal manifestations consisted of haematuria (macroscopic in 3 patients), proteinuria (heavy in 5), renal insufficiency (4) and hypertension (2). Decreased C3 levels, cryoglobulins, and antinuclear factors were frequent. Cultures of blood and cerebrospinal fluid provided growth mainly of S. epidermidis. Renal biopsy revealed endocapillary GN (1), membranoproliferative GN (1) and endocapillary/extracapillary GN with crescents (2). All patients received antibiotics i.v. Complete recovery was observed in three of four patients in whom the shunt was totally removed, supported by transient external drainage of cerebrospinal fluid, and followed by placement of a ventriculoperitoneal shunt. One child with delayed diagnosis, presenting with a serum creatinine of 3.2 mg/dl, hypertension, and severe scarring on renal biopsy, rapidly progressed to irreversible ESRD within 5 months. Two patients without and only partial removal of the shunt died subsequently from sepsis. CONCLUSIONS: The renal outcome of shunt nephritis is good if early diagnosis and treatment is provided including i.v. antibiotics and total removal of the infected shunt. The possible progression to ESRD requires frequent nephrological monitoring of patients with ventriculoatrial shunts.

Adult↗
PubMed1997

Renal granulomas in systemic vasculitis. EC/BCR Project for ANCA-Assay Standardization.

Renal granulomas are a relatively infrequent finding in the kidney biopsy. They have been described in a number of syndromes such as Wegener's granulomatosis, anti-GBM glomerulonephritis, and sarcoidosis, and are commonly believed to be indicative of a fulminant clinical course. In leading textbooks, diverse definitions of renal granulomas are presented, which has led to controversies in identifying them. This, in combination with their rare occurrence, makes it difficult for the general pathologist to identify them. We present the clinical data of 16 patients with renal granulomas, from a total group of 157 patients with systemic vasculitis. Their renal functioning was not significantly different from the other 141 patients in whose renal biopsies renal granulomas were present. Furthermore, we present two practical definitions for the recognition of renal granulomas in the kidney biopsy, and we show a number of examples of their various histopathological shapes.

Adult↗
PubMed1997

Rapidly progressive IgA nephropathy with anti-myeloperoxidase antibodies benefits from immunosuppression.

CLINICAL OBSERVATIONS: Three patients with previous pulmonary infections were recently admitted with rapidly progressive renal failure. Renal biopsy showed crescentic glomerulonephritis with deposits of IgA, C3c and C3d. Serology disclosed P-ANCA with high-titer anti-myeloperoxidase antibodies. Two out of three patients became dialysis dependent despite immunosuppression with methylprednisolone and cyclophosphamide. Renal function improved in both patients after 2 weeks and 9 months, respectively, permitting termination of hemodialysis. All patients benefited from immunosuppressive treatment which is currently still being continued. CONCLUSION: The data suggest that early immunosuppression is beneficial in patients presenting with crescentic rapidly progressive IgA GN and anti-myeloperoxidase antibodies, which may represent a novel subset of crescentic IgA GN associated with high-titer anti-myeloperoxidase antibodies constituting an overlap group between microscopic polyangiitis and IgA GN.

Aged↗
PubMed1996

Intravenous somatic gene transfer with antisense tissue factor restores blood flow by reducing tumor necrosis factor-induced tissue factor expression and fibrin deposition in mouse meth-A sarcoma.

Fibrin is deposited on the endothelial cell surface in the vasculature of murine methylcholanthrene A-induced sarcomas after injection of tumor necrosis factor (TNF). Capillary endothelial cells of the tumor vascular bed become positive for tissue factor after TNF injection, based on immunocytochemistry and in situ hybridization. Intravascular clot formation was not dependent on tissue factor derived from tumor cells, since in vessels of tumors not expressing tissue factor, TNF also induced fibrin/fibrinogen deposition. However, the time course of fibrin/fibrinogen deposition after TNF differed in tumors expressing no, little, or greater amounts of tissue factor. Fibrin/fibrinogen deposition was more rapid in tumors in which the neoplastic cells expressed tissue factor than in tumors not expressing tissue factor. In the tumors not expressing tissue factor, activation of coagulation was dependent on TNF-induced synthesis of tissue factor by host cells, i.e., endothelium or monocytes/macrophages. Intravenous somatic gene transfer with tissue factor cDNA in the antisense orientation (but not sense or vector alone) reduced intravascular fibrin/fibrinogen deposition and restored blood flow to the tumor, showing that de novo tissue factor expression is central in TNF-induced activation of the coagulation mechanism.

Animals↗
PubMed1996

Concomitant overexpression of the EGFR and erbB-2 genes in renal cell carcinoma (RCC) is correlated with dedifferentiation and metastasis.

Gene amplification or structural alteration of different erbB genes exerts a transforming effect in a variety of human neoplasms. Overexpression of the EGF receptor is associated with tumor initiation and progression of renal cell carcinoma (RCC). However, the role of erbB-2 in these processes remains unknown. We investigated 34 renal cell carcinomas for gene amplification and expression of the EGFR and erbB-2 genes at the mRNA and protein level and their relationship to pathological and clinical parameters. No amplification of both genes has been observed. However, high expression of the EGF receptor protein and p185erbB2 was frequent in RCC and statistically significantly related to higher tumor grades. We could demonstrate a close correlation of p185erbB2 overexpression with high EGF receptor levels. Co-overexpression of both receptor types was significantly associated with metastatic disease. Our results suggest a synergistic involvement of both EGF receptor and p185erbB2 in the progression of RCC.

Blotting, Southern↗
PubMed1996

X-chromosome methylation ratios as indicators of chromosomal activity: evidence of intraindividual divergencies among tissues of different embryonal origin.

To test whether the differentiation events that lead to the embryonal layers and their derived organs produce divergent X-chromosome activation ratios among the different tissues, the X-chromosome activation ratios in leucocytes and muscle (mesodermal origin), thyroid gland (endodermal origin) and medulla of the suprarenal glands (ectodermal origin) from ten deceased females were surveyed. Analysis of the degree of the methylation of the polymorphic alleles recognized by the probes M27beta and pSPT-PGK showed that the ratios for the medulla of the suprarenals correlated well with those of all other tissues except for leucocytes; the thyroid gland showed limited correlation with muscle, whereas leucocytes showed correlation only with muscle. The results of this preliminary study suggest that differentiation events result in considerable variation in the activation ratios in different tissues. As a consequence caution should be taken in extrapolating from the activation ratios observed in leucocytes or fibroblasts to tissues of endodermal or ectodermal origin.

Aged↗
PubMed1996

[Effect of complement modulation with the soluble complement receptor sCR1 on survival and function of kidney xenotransplant. An experimental study with a new guinea pig to rate transplant model].

In this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 +/- 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.

Animals↗
PubMed1996

Nephrotic syndrome, hypertension, and adrenal failure in atypical Cockayne syndrome.

This report describes a boy with an atypical severe from of Cockayne syndrome type II manifesting in infancy. He developed nephrotic syndrome at the age of 4.7 years and a hypertensive crisis with hemiparesis at 5.4 years. Renal biopsy revealed focal segmental glomerulosclerosis, which was confirmed at autopsy. Adrenocortical failure was also present. The course was characterized by frequent infections and an episode of myocarditis. The boy died at the age of 6.0 years after rapid neurological deterioration accompanied by renal insufficiency. Autopsy disclosed cerebral leukodystrophy compatible with Cockayne syndrome.

Adrenal Cortex Diseases↗
PubMed1996

Early increase in blood pressure and diastolic left ventricular malfunction in patients with glomerulonephritis.

In patients with diabetic nephropathy blood pressure increases progressively before the conventional threshold of normal blood pressure (140/90 mm Hg) is transgressed. In patients with glomerulonephritis, no information on this point is available. To clarify this issue we sequentially examined 20 untreated patients with biopsy-proven primary chronic glomerulonephritis (GN) who had casual blood pressure below 140/90 mm Hg and normal GFR by inulin clearance. Patients were compared with normotensive healthy controls who were matched for BMI, gender and age. We measured ambulatory 24-hour blood pressure (SpaceLab system), echocardiography (ASE criteria, Acuson 128 XP 10), CIn and CPAH, urinary Na excretion, PRA and insulin concentration. In patients with GN, the median 24 hour (P < 0.0005), daytime (P < 0.001) and nocturnal sleeping time (P < 0.0001) MAP values were significantly higher than in matched controls (daytime, mean 97 mm Hg, 85 to 106 GN vs. 89 controls range 82 to 102; nocturnal sleeping time, mean 80.3 mm Hg, 71 to 89.5 GN vs. 73 controls, range 63 to 84). Echocardiographic examination showed significantly greater posterior wall thickness (P < 0.01) and ventricular septal thickness (P < 0.003). In addition the early diastolic to late diastolic (E/A) ratio of mitral valve peak inflow velocity was significantly (P < 0.0008) lower in patients. The data point to left ventricular wall thickening accompanied by LV diastolic malfunction. The study documents elevated ambulatory blood pressure in patients with primary chronic glomerulonephritis despite normal body weight and normal GFR. This is associated with evidence of target organ damage in the heart. The findings suggest that in patients with glomerulonephritis blood pressure increases initially within the normotensive range. This observation in conjunction with evidence of early target organ changes provides an argument for early antihypertensive intervention, but controlled trials to test efficacy and safety of this proposal are necessary.

Adult↗
PubMed1996

Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNF alpha therapy.

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-alpha) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-alpha (rhTNF-alpha). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-alpha therapy was poor. Only one patient with isolated intraarterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-alpha therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.

Adult↗
PubMed1996

The renal histopathology in systemic vasculitis: an international survey study of inter- and intra-observer agreement.

In order to relate histopathological findings of the kidney in systemic vasculitis to renal outcome, scoring of various morphological parameters is necessary. Therefore, we conducted a standardization study for evaluating renal biopsies from patients with systemic vasculitis. Four experienced renal pathologists from four European centres joined in the study. A scoring protocol was devised that required the observers to score an extensive number of histopathological lesions either quantitatively (as a percentage of the total number of glomeruli) or dichotomously (on a present/absent scale). Twenty renal biopsies were scored individually by all the observers, from which the inter-observer variability was analysed. Ten randomly chosen biopsies were scored again, in order to obtain the intra-observer variability. For inter-observer agreement, the evaluation of the quantitative variables was satisfactory for both rounds (0.55 < or = Kendall's W < or = 0.95 and 0.59 < or = W < or = 0.96, respectively, with all P < 0.05). However, the inter-observer agreement for the dichotomous data was poor (kappa < or = 0.30 in more than half of the parameters in both rounds). Also the data on intra-observer agreement showed more favourable results for the analysis of the quantitative data (Pearson's r > 0.45 in more than 85% of the variables in both rounds) than for the dichotomous scoring system (kappa < or = 0.30 in more than half of the variables). It is concluded that even between experienced renal pathologists discrepancies occur in scoring kidney biopsies. Inter- and intra-observer agreement is greater if a quantitative method for reviewing the biopsies is applied that requires the observers to score the tissue specimens systematically.

Biopsy↗
PubMed1996

Receptors for advance glycation end-products (AGE) - expression by endothelial cells in non-diabetic uraemic patients.

BACKGROUND: Cellular actions of advanced glycation end-products (AGE) are mediated by a receptor for AGE (RAGE), a novel integral membrane protein. Immunohistochemical studies show only low-level RAGE antigen expression in endothelial cells. Design. It was the purposes of the study to compare expression of RAGE antigen by endothelial cells in non-diabetic uraemic patients (n=8) with non-uraemic controls (n=11). Samples of arterial tissue were obtained at the time of renal transplantation (in uraemic patients) and abdominal surgery (in controls). RAGE antigen was visualized using guinea-pig anti-RAGE IgG and PAP technique. RESULTS: Marked staining for RAGE was noted in endothelial cells, both arterial endothelium and endothelium of vasa vasorum of normoglycaemic uraemic patients, but was not demonstrable in endothelial cells of large arteries and only faintly expressed in vasa vasorum of non-uraemic individuals. CONCLUSION: Normal endothelial cells do not constitually express RAGE antigen; in contrast it is expressed by arterial and capillary endothelial cells of uraemic patients. The observation is of note in view of the putative role of AGE of causing atherosclerotic and non-atherosclerotic vascular lesions.

Adult↗
PubMed1996

Effect of longterm placebo controlled calcium supplementation on sigmoidal cell proliferation in patients with sporadic adenomatous polyps.

A longterm, double blind intervention trial was undertaken in patients with sporadic adenoma treated by polypectomy to investigate the putative role of calcium as a protective factor in colon carcinogenesis. The aim of the study was to assess the effect of a daily dietary supplementation of 2 g calcium over nine months on cell proliferation measured as proliferation index in colonic mucosa. A total of 48 patients were entered into the study of which 30 were fully compliant. After intervention proliferation index % (mean (SEM) in colonic epithelium was decreased in both the calcium (13.5 (1.5) to 11.4 (1.2)) and the placebo group (13.7 (0.9) to 10.8 (1.1)). The difference in the change between the two groups was not significant (p = 0.7). Changes in proliferation index % of crypt compartments were also not significantly different between the two groups. A significantly positive correlation between soluble calcium in faeces and the total proliferation index % in colonic epithelium at baseline and after intervention (r = 0.54, p < 0.01, r = 0.50, p < 0.01 respectively) suggests that an increase of free luminal calcium alone is insufficient for inhibition of cellular proliferation.

Adenomatous Polyposis Coli↗
PubMed1996

Excessive testosterone production in a patient with Nelson syndrome and bilateral testicular tumors.

Bilateral primary testicular tumors are rare and usually consist of either interstitial cells or hypertrophic testicular adrenal remnant tissue. Their differentiation on clinical presentation and histologic examination remains difficult but is essential because of the different therapeutic approaches. We report a rare case of excessive testosterone production by bilateral testicular tumors in a patient with Nelson syndrome (ACTH-secreting pituitary adenoma after bilateral adrenalectomy in patients with Cushing's disease). Increased ACTH stimulation in this patient supports the thesis of pluripotent cells within the testis which can undergo differentiation to cells which are not only morphologically similar to Leydig cells but also have the functional property of these cells. Our clinical findings support the diagnosis of hyperplasia of adrenal remnant or pluripotent cells rather than a true Leydig cell tumor. We emphasize the need for hormonal evaluations which should be assessed in the context of the size of these nodular tumors prior to therapeutic decisions. In cases with elevated serum ACTH and small nodular hyperplasia, we would favor a 'wait-and-see' strategy with appropriate hormonal therapy. In large tumors with clinical signs of hormonal activity, patient noncompliance with steroid replacement regimens or with local symptoms, scrotal exploration and tumor enucleation are indicated.

Adrenalectomy↗