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Biomedical subjects

R Waldherr

Publications and source records attributed to R Waldherr.

At least 91 records · Page 5Linked to original sources
PubMed1994

[Schistosomiasis and signet ring cell carcinoma of the ileocecal valve].

A 24-year-old male Egyptian complained of cramp-like upper abdominal discomfort and weight loss (3 kg) over 4 weeks. Physical examination merely gave evidence of the weight loss and of a slightly prominent gas-filled abdomen, mild diffuse abdominal tenderness and considerable borborygmus. Radiology of the intestines revealed chronic subileus of the small intestine caused by stenosis of the ileocaecal valve, which was impassable by coloscope. Biopsy suggested schistosomiasis of the ileocaecal valve. Examination of the resected ileocaecum showed a typical signet-ring carcinoma of the ileocaecal valve which had infiltrated all layers but had not metastasised to the regional lymph nodes (pT3, N0, M0). Typical eggs of Schistosoma haematobium were present in the mucosa of the tumour segment and of the neighbouring tissues. It is possible that chronic intestinal schistosomiasis is a potentially precancerous condition, similar to schistosomiasis of the urinary bladder.

Adult↗
PubMed1994

Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model.

There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea-pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline-treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 +/- 2.1 min. Administration of a single 60 U/kg i.v. bolus of CVF significantly prolonged renal graft survival to 20.4 +/- 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 +/- 2.3 h was achieved. The grafts functioned only over periods of 2.5 +/- 0.3 and 2.3 +/- 0.2 h, respectively. No complications of sCR1 were noted. We concluded that complement inhibition by sCR1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.

Animals↗
PubMed1994

Enhancement of ethanol induced rectal mucosal hyper regeneration with age in F344 rats.

Experimental studies in rats have shown an independent stimulation of rectal cell turnover by either chronic ethanol consumption or age. In this study the combined effect of these two factors on colorectal cell regeneration has been investigated. Ninety male F344 rats aged 2, 12, and 22 months were pair fed nutritionally adequate liquid diets containing 36% of total energy either as ethanol or isoenergetic carbohydrates. After four weeks of feeding, colorectal crypt cell production rates were measured using a stathmokinetic technique with vincristine. While age by itself did not affect colorectal cell renewal, chronic ethanol consumption stimulated rectal, but not colonic crypt cell production rate in an age dependent manner. While no significant effect of ethanol was noted in young animals, cell proliferation was significantly enhanced in middle aged animals by 81% (4.1 (2.7-5.5) v 7.4 (6.0-8.7) cells/crypt/hour, p < 0.001) and in old animals by 138% (4.5 (3.3-5.6) v 10.7 (8.9-12.4) cells/crypt/hour, p < 0.001) after ethanol ingestion. Because acetaldehyde, the first and most toxic metabolite of ethanol, has been detected in the colorectal mucosa and may lead to tissue injury influencing cell regeneration, acetaldehyde concentrations have been measured in the colons of 15 male F344 rats of various ages after an acute intraperitoneal dose of ethanol (2.5 g/kg bodyweight). There was a significant positive correlation between crypt cell production rate and acetaldehyde concentrations measured in the distal and proximal colon after an acute dose of ethanol (r = 0.5955, p < 0.005). These data clearly show that the ethanol mediated stimulation of cell regeneration in the rectum is age dependent. As reported earlier, there was found indirect evidence that acetaldehyde participates in the pathogenesis of rectal hyperregeneration after chronic alcohol consumption. This hyperregeneration of the rectal mucosa after alcohol drinking could by itself favour carcinogenesis, which is especially relevant in old age.

Acetaldehyde↗
PubMed1994

Outcome and prognostic determinants in the hemolytic uremic syndrome of children.

The late outcome in 89 children with the hemolytic-uremic syndrome (HUS) observed from 1971 to 1988 was analyzed up to 17 years after onset in relationship to various clinical and pathologic features at the onset of the disease. In the first 3 months after onset (acute phase) 69% of all children needed dialysis therapy. Fifteen children died, 9 during the acute phase and 6 subsequently. All surviving patients except 7 were reexamined and divided into five prognostic categories: recovery, residual renal symptoms with normal kidney function, moderate renal insufficiency, preterminal chronic renal failure (CRF) and end-stage renal disease (ESRD). The rate of recovery calculated by the life table method increased from 35% after 10 years in 1971-1979 to 68% in 1980-1988 (p < 0.001); it was lower in infants than in older children (44 vs. 63%; nonsignificant). Children with atypical HUS experienced more often preterminal CRF, ESRD or death than those with a typical (postenteropathic) form (33 vs. 17%; p < 0.05). If oliguria lasted < 7 days, 74% of patients recovered after 10 years versus 13% in the case of oliguria > 14 days or anuria > 7 days (p < 0.0005). The rate of recovery was also significantly smaller with the duration of dialysis treatment > 7 days, central nervous system involvement and requirement for antihypertensive therapy. In the entire series 7 patients developed preterminal CRF and 5 ESRD. Of 27 cases serially followed for 5-10 years after onset, a stable course was noted in 16, a subsequent improvement in 8 and deterioration in 3 leading to ESRD in 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Central Nervous System Diseases↗
PubMed1994

Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice.

Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells over-expressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.

Animals↗
PubMed1994

Vascular origin of Kaposi's sarcoma. Expression of leukocyte adhesion molecule-1, thrombomodulin, and tissue factor.

We studied seven cases of Kaposi's sarcomas (KS) obtained from patients with AIDS and one KS from a patient without HIV infection. Antigen expression was studied by immunocytochemistry and mRNA expression by in situ hybridisation. The markers tested were endothelial leukocyte adhesion molecule-1, thrombomodulin, and tissue factor. In all tumors (AIDS and non-AIDS associated) these markers reacted positive, indicating transcription and translation of these genes in KS. The synthesis and expression of tissue factor and thrombomodulin suggests that KS is a tumor that has tissue factor-mediated thrombin formation under the control of thrombomodulin. The expression of thrombomodulin and endothelial leukocyte adhesion molecule-1 provides evidence for the vascular origin of KS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A role for histones and ubiquitin in lupus nephritis?

Glomerulonephritis frequently develops in Systemic lupus erythematosus (SLE) but the pathogenesis is still poorly understood. Experimental evidence now suggests that histones can participate in immune complex formation in lupus nephritis. In a retrospective study, using samples from Northern and Southern Europe, Japan and South America, we searched for glomerular deposits of histones, both in native and ubiquitinated forms, in renal biopsy specimens from 48 patients with SLE and 70 cases of glomerulonephritis from patients without SLE. Positive glomerular immunofluorescent staining was revealed with rabbit antibodies to synthetic peptide 1-21 of histone H3, 22-45 of ubiquitin and to the branched region of ubiquitinated histone H2A (U-H2A) in 65% (31/48), 29% (14/48) and 54% (26/48) of the cases of SLE respectively. In total positive staining with at least one of the antibodies was seen in 36/48 (75%) cases. The staining was granular in nature and was present in capillary and mesangial areas. Only 3% (2/70) of non-SLE renal biopsies revealed positive staining with the above antibodies. None of the biopsy specimens from SLE patients were positive for ss- or ds-DNA, when tested with intercalating dyes. Serum samples were available from 15/48 SLE cases and were analysed with peptides and parent proteins by ELISA; epitopes in the N-terminal regions of core histones and in the C-terminus of histone H1 were often recognised by IgG antibodies in SLE sera, as was ubiquitin and the branched octapeptide of U-H2A. These results support the notion that the nuclear autoantigens histone and ubiquitin may be involved in the induction of glomerulonephritis in human SLE.

Animals↗
PubMed1994

Prevalence of immunecomplex-associated glomerulonephritis in hypertensive subjects.

Glomerulonephritis demonstrable by immunohistochemistry may be present at post mortem in many patients without overt renal diseases. Systematic renal biopsies in severely hypertensive patients have shown a high prevalence of clinically undiagnosed glomerulonephritis. We have examined the kidneys of 423 consecutive subjects who came to post mortem and full-filled criteria for the diagnosis of hypertension. Patients were considered to be hypertensive if this had been clinically documented during life or if the heart weight/body weight ratio was > 0.005 in the absence of known other causes of cardiac hypertrophy. Normotensive controls were selected on the basis of clinically documented normal BP or a heart weight/body weight ratio of < 0.001. Kidneys were examined by immunohistology (PAP technique using human IgA, IgG, IgM antibodies). Excluding cases with liver cirrhosis, only two of the 337 patients with hypertension (= 0.6%) and none of the 49 normotensive patients had mesangial IgA deposits (P = 0.77). This finding argues against the frequent occurrence of latent glomerulonephritis in elderly patients with manifest hypertension.

Adolescent↗
PubMed1994

Postinfectious glomerulonephritis--is there a link to alcoholism?

From January 1984 to May 1993, we observed 30 cases of postinfectious glomerulonephritis (GN)--endocapillary, exudative GN with humps (23 males, 7 females; median age 49 years; range 17-77). They represented 4.5% of all renal biopsies. Crescents were present in 9/26 who had renal biopsies (35%) and there was a mesangioproliferative pattern in 14 (54%). Seventeen of the 30 patients (57%) were alcoholics by history and biochemistry. Cirrhosis was present in 8/17 (47%), but alcoholic hepatitis in none. Nine of the 17 alcoholic (53%) but none of the non-alcoholic patients developed chronic renal failure. Adverse renal prognosis was significantly correlated to alcoholism. We conclude that (i) alcoholism is common in patients with postinfectious GN, and, (ii) alcoholism adversely affects renal prognosis in patients with postinfectious GN.

Adolescent↗
PubMed1994

[Local recurrence after organ saving kidney tumor surgery].

Although excellent survival rates for nephron-sparing surgery in mandatory indications (solitary kidney, bilateral renal neoplasms) have been documented, parenchymasparing surgery in elective indications (normal contralateral kidney) is a point of controversy. Local tumor recurrence is the most important argument against this approach. From January 1971 to December 1989, 107 patients suffering from renal cell carcinoma in solitary kidneys or bilateral renal carcinoma underwent nephron-sparing surgery. Thirteen patients (12%) suffered from local recurrence between 4 and 112 months after tumor resection. A high proportion of these recurrences were seen within the first 2 years after resection, followed by a almost linear increase thereafter. Thus-there are possibly two different entities for local recurrence. A correlation between tumor grade and interval from resection to local recurrence could be found, with a long average interval for grade 1 tumors--longer than the published follow-up times for patients undergoing elective tumor resections. Although most of the patients described in this report do not fulfil the surgical criteria for elective resection, we cannot recommend parenchyma-sparing surgery in elective indications.

Adult↗
PubMed1993

Expression of cytokines and growth factors in human glomerulonephritides.

Numerous experimental studies point to the potential role of cytokines and growth factors in the pathogenesis of renal disease. However, from the various autocrine and paracrine mediators identified in vitro and in animal models, so far only a few have been demonstrated in selected human glomerulopathies. We examined two types of glomerulonephritis (GN): extracapillary GN with anti-neutrophil cytoplasmic autoantibodies (ANCA), an example of an acute form of GN, and mesangial IgA GN, usually a chronic form of GN, with immunocytochemistry, in situ hybridization and the polymerase chain reaction. Normal renal tissue from tumour nephrectomies served as a control. In ANCA-positive GN with active renal lesions (crescents, glomerular and vascular necrosis), infiltrating mononuclear cells in glomeruli and in the interstitium expressed interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha, IL-2, interferon (IFN)-gamma, platelet-derived growth factor (PDGF) and transforming growth factor (TGF)-beta. Cytokine expression was also observed in activated resident cells, including endothelial cells, capsular epithelial cells, smooth muscle cells of vessel walls, fibroblasts and some tubular epithelial cells. In addition, we noted an increase in the cytokine and growth factor receptors TNF-R, IL-1R type II, IL-2R, IFN-gamma R and PDGF beta-R. In contrast, in mesangial IgA-GN, IL-1 beta, TNF-alpha, IFN-gamma and IL-2 were usually absent in glomeruli. Mesangial expansion in this disorder was accompanied by an increased expression of PDGF, PDGF beta-R, TGF-beta and IL-6 in mesangial areas. In both conditions a good correlation was observed between cytokine expression at the mRNA (in situ hybridization) and protein level (immunocytochemistry).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Scleroderma renal crisis as a presenting feature in the absence of skin involvement.

A 56-year-old man was admitted to the nephrology unit with a short (6-week) history of severe hypertension that necessitated renal replacement therapy within 7 days after admission. Renal biopsy showed features of thrombotic microangiopathy in arterioles and small arteries with occluding thrombi. The skin was unremarkable at the time of admission. Progressive skin lesions with scleroderma, telangiectasia, sclerodactyly, and generalized cutaneous sclerosis developed within 4 weeks and the specific skin changes were found on skin biopsy. On admission antinuclear antibody titers were high (1:10, 240) with a nucleolar pattern, and PM-Scl antibodies (1:5, 120) were present. In the present case the diagnosis of scleroderma renal crisis was made in vivo by renal biopsy. Renal and skin biopsies documented that renal lesions may precede the clinically manifest skin lesions of progressive systemic sclerosis.

Biopsy↗
PubMed1993

In situ production of TNF-alpha, IL-1 beta and IL-2R in ANCA-positive glomerulonephritis.

Humoral and cellular immune mechanisms are thought to be involved in various forms of vasculitis and glomerulonephritis. Recent clinical and experimental results point to a role of cytokines in ANCA-positive vasculitides. We analyzed tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-2 receptors (IL-2R) in renal biopsies and in plasma from 22 patients with Wegener's granulomatosis and microscopic polyangiitis. Kidney biopsies were examined by immunocytochemistry, polymerase chain reaction and in situ hybridization. Immunoreactive TNF-alpha, IL-1 beta and/or IL-2R positive infiltrating cells were observed in 21 of 22 biopsies. TNF-alpha, IL-1 beta and IL-2R staining was evident in the interstitium and at periglomerular and perivascular sites. The number of positive cells was markedly increased in biopsies with active lesions. Positive cells were also present in cellular and fibrocellular crescents, surrounding tuft necrosis and in the walls of arteries and arterioles with acute vasculitic lesion. Some tubular epithelial cells stained for TNF-alpha and IL-1 beta. TNF-alpha, IL-1 beta and IL-2R positive infiltrating cells correlated with the presence of histologically active renal lesions. The evaluation of TNF-alpha and IL-1 beta expression at the mRNA level assessed by the polymerase chain reaction demonstrated specific transcripts for TNF-alpha and IL-1 beta in all six cases analyzed. In situ hybridization studies showed an increased expression of mRNA for TNF-alpha and IL-1 beta in infiltrating mononuclear cells, in epithelial cells of Bowman's capsule and in some tubules, predominantly of patients with active renal lesions. The results at the mRNA level correlated with the immunocytochemical findings. Compared to healthy individuals higher TNF-alpha plasma levels were observed in patients with vasculitis (34.4 +/- 16.6 pg/ml (SEM) vs. 1.9 +/- 0.7 pg/ml in controls; P < 0.01). All patients presented a marked increase in sIL-2R plasma levels (3512 +/- 485 U/ml vs. 397 +/- 21 U/ml in healthy controls; P < 0.001). IL-1 beta was not detected in most plasma samples. Elevated TNF-alpha and sIL-2R plasma levels were related to active renal lesions. Our study clearly demonstrates that in ANCA-positive vasculitis TNF-alpha and IL-1 beta are produced in situ by activated infiltrating mononuclear cells and resident renal cells. Intrarenal localization of cytokine producing cells and the correlation between cytokine production and histological signs of activity suggest that TNF-alpha and IL-1 beta are important locally acting mediators in the vasculitic/glomerulonephritic process.

Adolescent↗
PubMed1993

Autosomal dominant polycystic kidney disease (ADPKD)--mechanisms of cyst formation and renal failure.

None of the hypotheses proposed so far to explain cyst formation in autosomal dominant polycystic kidney disease (ADPKD) is entirely satisfactory, e.g. the theory of tubular obstruction by intraluminal polyps or dilatation of nephron segments as a consequence of abnormal compliance of the basement membrane. Recent in vitro studies show that (i) synthesis of basement membrane material is abnormal and that (ii) the direction of transepithelial resorptive flux into a secretory mode is reversed as a consequence of faulty insertion of Na, K-ATP'ase into the luminal membrane. It remains unclear why cystic transformation of a few percent of nephrons should cause endstage renal failure. Our clinical and experimental studies do not provide evidence to support some hypotheses proposed in the past, i.e. that renal parenchyma is compressed by expanding cysts and that glomeruli are overperfused. Our histological studies show that progression to endstage renal failure is associated with (i) progressive arteriolar lesions (out of proportion to the vascular lesions seen in extrarenal vascular beds; and (ii) progressive interstitial fibrosis. It appears that fibroblasts in ADPKD are particularly sensitive to platelet derived growth factor (PDGF) which is secreted by epithelial cells of the cyst wall in a paracrine fashion. In contrast to previous opinion, which was presumably skewed by ascertainment bias, it appears that not all, and perhaps not even a majority, of ADPKD patients progress to endstage renal failure. Factors related to progression are gender, family history and hypertension. Both abnormal sodium excretion and inappropriate renin secretion play a role in the genesis of hypertension. Elevated blood pressure, albeit within the normotensive range, is demonstrable even in prepubertal children. The involvement of renin in renal vasoconstriction of normotensive ADPKD patients suggests a particular role of ACE inhibitors in the management of these patients.

Dilatation, Pathologic↗
PubMed1993

Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people.

Adolescent↗