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W Bernauer

Publications and source records attributed to W Bernauer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cells perpetuating the inflammatory response in scleritis.

Scleritis can be a destructive disease frequently associated with autoimmune disorders. It is believed that primary vasculitis plays an important role in its pathogenesis, but little is known about the cellular effector mechanisms. The purpose of this study was to analyse the inflammatory cellular infiltrate in scleritis. Six episcleral biopsies and two enucleated eyes were studied. The episcleral biopsies were taken from patients with nodular scleritis. In one patient enucleation was done after perforation in anterior necrotising scleritis and, in the other after misdiagnosis of posterior scleritis as intraocular tumour. Morphological criteria and immunohistochemical methods were used to characterise the inflammatory cellular infiltrate. The inflammatory cells infiltrating the episcleral tissue were mainly T lymphocytes and macrophages. There was a predominance of CD4 positive cells, but only few lymphocytes were activated (expressed IL-2 receptor). The cells infiltrating the scleral fibres in the enucleated eyes consisted in both cases predominantly of T cells. Clusters of B cells were found in perivascular areas. In circumscribed areas neutrophils, macrophages, and plasma cells were part of the scleral infiltrate. Signs of a granulomatous process with activated macrophages (epithelioid and giant cells) were present in necrotising scleritis. Expression of major histocompatibility class II molecules (MHC II) was found on lymphocytes and rarely on macrophages. Signs of primary vasculitis were not found in any of the specimens. The cellular infiltrate in scleritis shows, at least at certain stages, features compatible with a T cell mediated (autoimmune) disorder, which may have major therapeutic implications.

Adult↗
PubMed1994

[Immunohistologic findings in chronic cicatricial conjunctivitis].

BACKGROUND: Chronic progressive conjunctival cicatrization is found in some mucocutaneous disorders (cicatricial pemphigoid, linear IgA disease) and after long-term treatment with certain topical medications (pseudo-pemphigoid). Little is known about the mechanisms of conjunctival shrinkage, and therapy for these conditions remains difficult. OBJECTIVES: To elucidate the immune mechanisms and assess the main factors involved in conjunctival scar tissue formation in patients with chronic progressive conjunctival cicatrization. PATIENTS AND METHOD: We examined 14 bulbar conjunctival biopsy specimens from patients with chronic progressive conjunctival cicatrization (8 with benign mucous membrane pemphigoid confirmed by biopsy, 4 with the ocular features of benign mucous membrane pemphigoid and 2 with pseudopemphigoid) and 10 biopsies from matched healthy individuals: 1.5 mm sections of glycol methacrylate embedded tissue were analysed with the aid of a panel of monoclonal antibodies. MAIN RESULTS: Cell counts in the subepithelial substantia propria showed a marked increase in T-cells over normal controls (up to 30-fold). Among the T-cell subsets, there were more CD8 than CD4-positive cells observed. Only about 5% of the T-cells were activated (IL-2 receptor-positive). Macrophages were--as in normal tissues--the second most predominant cell. The absolute number was 2-3 times as high in diseased conjunctiva as in controls. There was increased expression of MHC II molecules on macrophages, lymphocytes und fibroblasts. The numbers of B-cells and NK were not increased. CONCLUSIONS: The analysis of the cellular infiltrate showed nonspecific immunopathological characteristics. Thus, the cellular infiltrate gives no explanation for the progressive cicatrization. There is evidence that soluble factors, especially fibrogenic cytokines, play an important role.

B-Lymphocytes↗
PubMed1993

Cytokines in the conjunctiva of acute and chronic mucous membrane pemphigoid: an immunohistochemical analysis.

The aim of this study was to evaluate the potential role of certain soluble factors in conjunctival scar tissue formation of pemphigoid patients. Epibulbar conjunctival biopsy specimens were taken from patients with acute ulcerative (n = 4), subacute (n = 8) and chronic (n = 8) mucous membrane pemphigoid and from twelve age-matched healthy individuals. The tissues were embedded in glycol methacrylate and analysed by immunohistochemical methods. Interleukin-2 (IL-2), interferon-gamma, transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), tumour necrosis factor-alpha and proliferating cells (as identified with the antibody Ki-67) were found in both pemphigoid patients and normal controls. Interleukin-4 was not found with this method in either normal or diseased conjunctiva. Significant differences between normal and diseased conjunctiva were found for TGF-beta and for proliferating cells, which were both increased in the acute disease group. More intense staining was found in the subacute disease group for IL-2, bFGF and PDGF. Our findings showed that a variety of cytokines were present in normal and diseased bulbar conjunctiva. Acute conjunctival disease in mucous membrane pemphigoid may indicate active scar tissue formation, implied by an increase in TGF-beta and the presence of proliferating fibroblasts.

Acute Disease↗
PubMed1993

The conjunctiva in acute and chronic mucous membrane pemphigoid. An immunohistochemical analysis.

BACKGROUND: The mechanism of chronic progressive conjunctival cicatrization in mucous membrane pemphigoid is not well understood, and current therapy is often of limited use. Rapid progression of cicatrization follows exacerbations of clinical inflammation, and the investigation of immune mechanisms related to disease activity may provide a clue for more effective therapeutic strategies. METHODS: The authors undertook an immunohistochemical study, using monoclonal and polyclonal antibodies in glycol methacrylate-embedded tissues, of epibulbar conjunctival biopsy specimens obtained from 20 patients with ocular cicatricial pemphigoid and from 12 matched healthy controls. The study patients were classified according to the ocular disease activity as acute ulcerative (n = 4), subacute (n = 8), and chronic (n = 8). RESULTS: The composition of the subepithelial cellular infiltrate varied with disease activity. Acute disease was characterized by an abundance of macrophages and neutrophils. The number of T lymphocytes was significantly raised in all the disease groups, but were most marked in subacute disease. Of the T-cell subsets, there were more CD8- than CD4-positive cells observed, except in acute disease where there were equal numbers. Only approximately 5% of the T cells in all disease groups were activated as demonstrated by expression of interleukin-2 receptor. There was increased expression of major histocompatibility complex class II (MHC II) molecules on macrophages, fibroblasts, and other cells in all the groups. The number of B cells and natural killer cells was not increased. Staining for the fibrogenic cytokines, transforming growth factor-beta (TGF-beta), platelet-derived growth factor, and basic fibroblast growth factor was found in both pemphigoid patients and control persons, but the intensity of TGF-beta staining was significantly greater in acute disease. CONCLUSIONS: The composition of the cellular infiltrate in the bulbar conjunctiva depends on clinical disease activity. The numbers of neutrophils and macrophages seem to reflect clinical disease activity. Fibrogenic cytokines, especially TGF-beta, may play an important role in the formation of conjunctival scar tissue.

Acute Disease↗
PubMed1993

Chronic progressive conjunctival cicatrisation.

The aim of this review is to demonstrate the spectrum of conditions encompassed by the term 'chronic progressive cicatrising conjunctivitis', to discuss mechanisms of conjunctival scar tissue formation and to describe the sequelae and therapeutic options in this potentially blinding condition. Chronic progressive cicatrising conjunctivitis is found in association with some mucocutaneous disorders (cicatricial pemphigoid, linear IgA disease), as part of paraneoplastic syndromes and after long-term treatment with certain systemic and topical medications (pseudo-pemphigoid). Recent studies on the conjunctiva of pemphigoid patients indicate that macrophages may play a pivotal role in chronic progressive conjunctival cicatrisation. They mediate the transition from inflammation to scar tissue by secretion of fibrogenic cytokines. There is evidence that similar mechanisms are involved in the other fibrosing conjunctival disorders. Sequelae of chronic conjunctival cicatrisation include the obstruction of lacrimal and meibomian glands, tear film alterations, trichiasis, keratopathy and blindness. Present possibilities and future options for the treatment of this condition are discussed.

Chronic Disease↗
PubMed1992

Failure to control AIDS-related CMV-retinitis with intravenous ganciclovir.

Between January 1988 and May 1991 intravenous ganciclovir (GCV) treatment was administered to eight male AIDS-patients with unilateral cytomegalovirus (CMV)-retinitis. Despite of continuous therapy with at least the recommended dose of GCV, three patients developed slowly progressive CMV-retinitis in the fellow eye after 4 to 13 months. The progression could not be stopped by GCV and thus bilateral blindness resulted after 12 to 22 months. The number of CD4-lymphocytes in the blood was reduced in all patients, but particularly in patients with progressive disease. Treatment failure was partly related to the duration of CMV-retinitis and partly to the degree of immunodeficiency. Intravenous treatment with GCV alone can not stop the progression of CMV-retinitis in long-term survivors and in those with advanced immunodeficiency.

AIDS-Related Opportunistic Infections↗
PubMed1992

[Morphologic aspects of therapy-resistant cytomegalovirus retinitis].

Intravenous ganciclovir treatment was performed in eight male AIDS patients with primary unilateral CMV-retinitis. Three patients developed slowly progressive CMV-retinitis in the fellow eye despite adequate dose of ganciclovir. These different CMV-manifestations are shown in a sequence of fundus pictures. Three types of CMV-lesions were observed in connection with this study. Untreated central lesions showed the aspect of crumbled cheese and ketchup. Untreated lesions in the peripherie were yellowish-white, granular, "dry" and showed in most cases no haemorrhages. Lesions appearing during treatment showed initially "dry" white opaque subretinal areas, turning later on to the typical aspect of untreated lesions. The progression could not be stopped by highdose ganciclovir i.v. and thus bilateral blindness resulted after 12 to 22 months. The level of CD4-lymphocytes in the blood was diminished in all patients, but much more in patients with progressive disease.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Bietti's corneal-retinal dystrophy. A 16-year progression.

Bietti's crystalline corneal-retinal dystrophy is characterized by deposits of crystals in the marginal cornea and the paracentral and peripapillary retina. To date, only three cases with long term follow-up have been reported. The case of another patient, who has been observed for 16 years, is reported here. The most striking morphologic feature during the period of examination was the diminution of the retinal crystals, an optical phenomenon that appears to be due to the advanced atrophy of the retinal pigment epithelium. The progressive course is documented photographically.

Adult↗
PubMed1991

Microvasculopathy in the ocular fundus after bone marrow transplantation.

OBJECTIVE: To determine the incidence and time course of retinal and optic-disk ischemia after bone marrow transplantation and to describe the clinical, fluorescein-angiographic, and histologic findings in patients with these ischemic fundus lesions. DESIGN: Prospective cohort study; standardized clinical and ophthalmologic evaluation of all patients before bone marrow transplantation and 3, 6, and 12 months after transplantation (and when indicated). SETTING: University hospitals in Basel, Switzerland. PATIENTS: Consecutive patients (127) treated with allogeneic or autologous bone marrow grafts. MAIN RESULTS: Thirteen of the 127 patients (10%; 95% Cl, 5% to 15%) had lesions of the ocular microcirculation. All patients had cotton-wool spots in the fundus of both eyes, and three patients also had bilateral optic-disk edema. Secondary changes included retinal hemorrhages and lipid deposits. The ischemic fundus lesions appeared during the first 6 months after transplantation and were reversible in 9 of the 13 patients. The lesions occurred only in patients who were treated with total body irradiation and were given cyclosporin A as prophylaxis for graft-versus-host disease. CONCLUSIONS: Ischemic fundus lesions are a frequent complication after bone marrow transplantation. They were only observed in patients treated with total body irradiation and cyclosporin A. This combination of therapy appears to have an additive effect on the development of ocular and possibly generalized microvascular lesions.

Adolescent↗
PubMed1991

Effect of exogenous adenosine deaminase on arrhythmias and the release of adenine nucleotide catabolites in isolated rat hearts with coronary occlusion and reperfusion.

In isolated perfused rat hearts with occlusion of the left coronary artery the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated with and without exogenous addition of adenosine deaminase. In the control experiments large amounts of the adenine nucleotide catabolites appeared in the perfusate during coronary reperfusion. The greater part was represented by adenosine and inosine. During the coronary occlusion itself only a minor increase in the release of adenine nucleotide catabolites was observed, compared with the basal release before the coronary occlusion. Depending on the duration of the coronary occlusion more or less severe tachyarrhythmias occurred during the reperfusion of the previously ischaemic myocardium. Reperfusion-induced ventricular fibrillation was associated with a significant increase in the release of adenine nucleotide catabolites, compared with non-fibrillating hearts. In the presence of exogenously-added adenosine deaminase the release of adenine nucleotide catabolites from reperfused hearts was further increased. Adenosine itself, however, almost completely disappeared from the perfusate. In adenosine-deaminase treated hearts the incidence of reperfusion-induced fibrillation increased, thereby contributing to the enhanced release of adenine nucleotide catabolites. However, the release was also increased by the enzyme when only the fibrillating hearts were considered, suggesting that rapid elimination of adenosine from the interstitial space also directly increases the release of adenine nucleotide catabolites from the heart.

Adenosine↗
PubMed1991

[CMV retinitis in AIDS--a pre-final complication?].

The appearance of cytomegalovirus (CMV) retinitis in AIDS is regarded as an unfavourable sign, it was even considered in the first years of the HIV-epidemic to be a pre-final complication. The survival period after diagnosis of the retinitis is under virostatic therapy generally given as several months, only exceptionally as more than a year. We report here 3 cases of CMV retinitis in AIDS having an unusually long duration of 14-24 months. The clinical and histological results with the pecularities (resistance to therapy, optic atrophy, retinal atrophy with detachment, atypical peripheral fundus lesions) are presented. The importance of ophthalmological care of HIV-patients is indicated and a screening procedure is suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[HIV patient and eyes].

A large percentage of patients in stage IV of HIV infection (CDC classification) show changes in the ocular fundus. Most frequent are functionally unimportant cotton-wool spots resulting from a HIV-associated microvasculopathy. Infectious retinitis due to opportunistic organisms is in most cases caused by cytomegalovirus (CMV). Untreated patients may become blind. In case of general or local treatment of cytomegalovirus retinitis with ganciclovir, sight may be preserved on a long-term basis. The ophthalmoscopic appearance of the typical changes and their histological substrate are presented, and modes of treatment are discussed. By direct ophthalmoscopy and visual acuity testing any physician can diagnose these fundus changes. Cotton-wool spots only require follow-up. In retinitis an ophthalmologist should be consulted. A screening procedure is suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1989

The effect of reserpine and guanethidine on carbohydrate metabolism in ischaemic rat myocardium.

We have investigated the role of endogenous catecholamines in myocardial carbohydrate metabolism in isolated, perfused rat hearts after left coronary artery occlusion for 30 min. A significant decrease in ATP and glycogen, and an increase in glucose-6-phosphate (G-6-P) content in the ischaemic myocardium was obtained. After depletion of the cardiac noradrenaline stores by reserpine or guanethidine pretreatment the increase in the G-6-P levels was very markedly enhanced, and the myocardial glycogen content of non-ischaemic control hearts was significantly increased by reserpine. However, the amount of glycogen broken down during the ischaemia in pretreated animals was similar to that in the ischaemic myocardium from control animals, and the decrease in the myocardial ATP was not altered by reserpine or guanethidine. Thus the well known release of noradrenaline during myocardial ischaemia is not an essential prerequisite for the activation of the ischaemic breakdown of glycogen. Rather, it is of importance for later steps in anaerobic carbohydrate metabolism, probably for the activation of phosphofructokinase, as suggested by the large ischaemic accumulation of G-6-P in noradrenaline depleted hearts.

Adenosine Triphosphate↗
PubMed1988

Antagonistic effects of alpha-adrenoceptor blocking agents on arrhythmias, enzyme release, and myocardial necrosis in isolated rat hearts with coronary occlusion and reperfusion.

In isolated perfused rat hearts reperfusion of the occluded left coronary artery led to arrhythmias, their severity depending on the duration of the foregoing period of myocardial ischaemia. Simultaneously, high activities of the myocardial enzyme creatine kinase (CK) were released into the perfusion fluid. Corynanthine, blocking mainly alpha 1-adrenoceptors, and rauwolscine, blocking mainly alpha 2-adrenoceptors, concentration-dependently antagonized the reperfusion-induced arrhythmias (3-30 mumol/l). The most severe kind of arrhythmia, i.e., ventricular fibrillation was completely prevented by 30 mumol/l of either drug. Also arrhythmias occurring already during the period of coronary occlusion were antagonized, as tested with corynanthine. The beta 1-adrenoceptor blocking agent metoprolol (1, and 10 mumol/l) had no effect at all against reperfusion arrhythmias, and the mainly alpha 1-adrenoceptor stimulating agent phenylephrine markedly increased the severity of these rhythm disturbances. The release of creatine kinase during the coronary reperfusion was significantly decreased by corynanthine, while the effect of rauwolscine was smaller and non-significant. Phenylephrine markedly increased the enzyme leakage from the myocardium. In all hearts the extent of the ischaemic and necrotic areas was determined. The percentage of the previously ischaemic area found necrotic at the end of the reperfusion, depended on the duration of the coronary occlusion. Corynanthine in a highly significant way decreased the area of myocardial necrosis, an effect obtained to some extent also with rauwolscine. The findings suggest that alpha-adrenoceptor stimulation is involved in the genesis of arrhythmias and myocardial damage associated with myocardial ischaemia and reperfusion. Possible mechanisms of action of corynanthine and rauwolscine are discussed, especially in view of the interrelationship between alpha-adrenoceptors and slow calcium channels.

Adrenergic beta-Antagonists↗
PubMed1987

The effect of the calcium antagonist gallopamil on arrhythmias and enzyme release in rat hearts with coronary ligation and reperfusion.

In intact rats, as well as in isolated perfused rat hearts, the calcium antagonist gallopamil reduced the severity of ischemic and reperfusion-induced arrhythmias. The effective doses, or concentrations, respectively, lay near the border to those producing atrioventricular block. The antiarrhythmic action was connected with a negative chronotropic effect, but was independent of the coronary vasodilating effect of the drug. Coronary occlusion, and especially reperfusion of the ischemic myocardium, led to the release of the enzyme creatine kinase (CK) from isolated hearts, and to the increase of the serum CK activity in intact rats. Gallopamil significantly reduced the reperfusion-induced enzyme release in isolated hearts. In intact rats the serum CK activities were higher in the presence of gallopamil, than without the drug. It is shown that gallopamil itself releases CK from the heart. This effect interferes with the action which gallopamil has on the enzyme release due to myocardial ischemia or reperfusion, respectively.

Animals↗
PubMed1986

The effect of ethanol on arrhythmias and myocardial necrosis in rats with coronary occlusion and reperfusion.

Ethanol (1, 2 and 3 g/kg, intravenously) decreased the severity of the ischemic arrhythmias in rats with ligation of the left coronary artery and subsequent coronary reperfusion. Reperfusion arrhythmias occurring intensively after occlusion times of 5 and 15 min, respectively, were however not antagonized. Similar results were obtained in isolated perfused rat hearts with final concentrations of 4 and 6 mg ethanol/ml. In rats with reperfusion after 60 min of coronary occlusion, 2 g ethanol/kg significantly reduced the percentage of the ischemic area which underwent necrosis. Moreover, the increase in the wet weight/dry weight ratio of the lungs, as a measure of edema formation, was prevented. The ethanol effects are discussed in the light of present knowledge of the pathogenesis of arrhythmias and myocardial necrosis in experimental myocardial infarction.

Animals↗