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Biomedical subjects

R Kettritz

Publications and source records attributed to R Kettritz.

32 records · Page 2Linked to original sources
PubMed1996

Disease activity and autoantibodies to endothelial cells in patients with Wegener's granulomatosis.

The purpose of this study was to assess the utility of antiendothelial cell antibodies (AECAs) in patients with active and inactive Wegener's granulomatosis. We studied 32 patients with Wegener's disease (clinical criteria and biopsy, as well as titers of antineutrophil cytoplasmic antibodies with a cytoplasmic pattern [cANCA]) over 4 years and compared their AECA values with those of 24 normal subjects similar in age and gender distribution, as well as with those of patients with chronic glomerulonephritis with or without dialysis and of patients with severe arteriosclerosis. We measured AECAs, cANCAs, C-reactive protein, erythrocyte sedimentation rate, proteinuria, and renal function in patients with active disease or in patients reactivating their disease. A time course with repeated AECAs was conducted over 27 months in 24 patients. The AECAs were measured with an enzyme-linked immunosorbent assay. The specificity was verified with immunofluorescent confocal microscopy, which showed the AECA epitopes to be within the cytoplasm of endothelial cells. Elevated AECA titers were found in all patients with active disease, not all of whom had positive cANCAs. Although elevated AECAs were also found in some patients with inactive disease, normal AECA values were seen only in patients with inactive disease. Patients with active disease entering remission showed a decrease in AECA titers, while patients entering a relapse increased their AECA titers. We conclude that AECAs are present in patients with Wegener's granulomatosis. To our knowledge, these are the first serial AECA observations. Our data suggest that AECAs are correlated with disease activity. Antiendothelial cell antibody values in the normal range strongly support remission. These findings may be of clinical utility in distinguishing relapse from concomitant illness.

Autoantibodies↗
PubMed1996

Apoptosis of endothelial cells induced by the neutrophil serine proteases proteinase 3 and elastase.

The pathogenesis of vasculitis associated with anti-neutrophil cytoplasmic antibodies is not established. The anti-neutrophil cytoplasmic antibody autoanigens proteinase 3 (PR3) and elastase induce detachment and cytolysis of endothelial cells in vitro. We investigated whether PR3 and elastase trigger endothelial cell apoptosis. Primary bovine pulmonary artery endothelial cells were treated with either PR3, elastase, or myeloperoxidase (MPO) and apoptosis assessed by four different methods. By the cell death detection enzyme-linked immunosorbent assay, DNA fragmentation increased to 208 +/- 84% or 153 +/- 27% of control with 1 micrograms/ml PR3 or elastase at 24 hours. By ultraviolet light microscopy, the percentage of apoptotic cells significantly increased (P < 0.05) with 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase at 6, 12, or 24 hours. Values at the 24-hour time point are 15.3 +/- 6.4% or 25.8 +/- 6.6% for 5 or 10 micrograms/ml PR3 and 13.9 +/- 3.6% or 20.7 +/- 1.8% for 25 or 50 micrograms/ml elastase compared with 2.2 +/- 1.2% for control. Similarly, with flow cytometry, 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase for 6, 12, or 24 hours demonstrated increasing apoptosis in a dose- and time-dependent manner with the highest values achieved at 24 hours (23.4 +/- 4.0% and 35.6% for 5 and 10 micrograms/ml PR3 and 31.8 +/- 4.0% and 47.8% for 25 and 50 micrograms/ml elastase compared with 7.9 +/- 2.2% in control). Typical DNA laddering was apparent from 6 to 24 hours at 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase. Myeloperoxidase did not induce cell apoptosis. Release of PR3 and elastase by activated neutrophils during acute inflammation, including anti-neutrophil cytoplasmic antibody-associated vasculitis, may result in vascular damage by endothelial cell apoptosis.

Animals↗
PubMed1995

Wegener's granulomatosis masquerading as breast cancer.

We describe a patient with Wegener's granulomatosis whose disease presented as pseudotumor of the orbit and a breast mass. Both findings were misinterpreted and errors in diagnosis resulted, despite the availability of rapid and accurate diagnostic tests for this disease. We report this case to emphasize the more unusual presentations of Wegener's granulomatosis.

Breast Neoplasms↗
PubMed1993

Prognostic factors in Wegener's granulomatosis.

We analysed data from 64 patients with Wegener's granulomatosis to determine predictor variables of outcome. The mean period of observation after the diagnosis had been established was 3.2 (range 0.1-11.2) years. At the time of diagnosis, 15 (23%) patients had only local symptoms. The disease was generalized to multiple organs in 49 (77%) patients. Renal biopsies were obtained in 33 patients; 13 (39%) had extracapillary glomerulonephritis, which was the most common renal lesion. All but three patients received immunosuppressive therapy. At time of follow-up, 17 (27%) patients were in complete, and 26 (40%) in partial remission. We employed a Kaplan Meier analysis to identify predictor variables of outcome. Renal involvement, initial creatinine concentration, serum albumin or total protein concentration, leukocyte count and erythrocyturia proved to be predictor variables. These variables may be of value in guiding the intensity of treatment in patients with Wegener's granulomatosis.

Adolescent↗
PubMed1990

[Wegener's granulomatosis and anti-cytoplasm antibodies].

20 patients with biopsy-proven Wegener's granulomatosis (WG) and 95 control patients underwent determination of anticytoplasmic antibodies (ACPA) by the indirect immunofluorescence technique to assess the specificity and sensitivity of ACPA for WG. Of 14 untreated patients with WG, 13 were ACPA-positive. All these patients became ACPA-negative under immunosuppressive treatment. 4 patients treated with immunosuppressive drugs and 2 patients in remission after termination of therapy had a negative ACPA-test. ACPA were detected in 9 patients of the control group (two patients with Henoch Schoenlein purpura, two patients with systemic vasculitis, 2 patients with systemic diseases, and 1 patient with systemic lupus erythematodes). With that we achieved a specificity of 90.5% and a sensitivity 65.0%. In conclusion the ACPA-determination is very helpful for diagnosis and follow-up of WG.

Adolescent↗
PubMed1988

[Cellular immune response and glomerulonephritis--their detection with the Tetamun intracutaneous test].

In the considerations of the pathogenesis of glomerulonephritis more importance is attributed to cellular immune reactions. The cell-mediated immune response was examined by means of the Tetamun intracutaneous test in 37 patients with histological verified glomerulonephritis, in 18 patients with non-glomerular renal diseases, and in 25 healthy probands. The influence of main disease, renal insufficiency, nephrotic syndrome and immunosuppressive therapy on the test results could be determined by proper group formation. A significant diminution of cell-mediated immune reactions by the glomerulonephritis was verified. The importance of this finding in the pathogenetic routes and a possible model are discussed.

Adult↗
PubMedDate not supplied

Cytomegalovirus colitis during mycophenolate mofetil therapy for Wegener's granulomatosis.

Cytomegalovirus (CMV) infection of the gastrointestinal tract is an increasingly recognized cause of morbidity and mortality during the course of HIV infection and in association with immunosuppressive pharmacotherapy. Mycophenolate mofetil, a novel immunosuppressive drug, is currently used in renal transplant recipients and is under evaluation for a variety of disorders. There is preliminary evidence to suggest that CMV reactivation may be more common during treatment with mycophenolate than with other immunosuppressive drugs. We present the case of a 59-year-old male with Wegener's granulomatosis who received mycophenolate and presented with guaiac-positive diarrhea 8 weeks after recovery from Salmonella brandenburg infection. CMV serology and assays for CMV antigens were entirely negative. Colonoscopy demonstrated pancolitis and examination of the specimens disclosed CMV infection. Ganciclovir was administered and the patient made an uneventful recovery. We discuss aspects of gastrointestinal CMV infection with an emphasis on pitfalls in diagnosis and the association with mycophenolate mofetil treatment. We also speculate as to the potential role of previous Salmonella infection and proinflammatory cytokines in CMV reactivation. In summary, when using mycophenolate, clinicians should be more aware of CMV reactivation and disease.

Antiviral Agents↗