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M Haubitz

Publications and source records attributed to M Haubitz.

36 records · Page 2Linked to original sources
PubMed1998

Cyclosporin for the prevention of disease reactivation in relapsing ANCA-associated vasculitis.

BACKGROUND: In patients with ANCA-associated vasculitis the frequent development of relapses after successful initial treatment remains a major therapeutic problem. Thus a long-term prophylactic therapy with low side-effect potential is needed. As recent data suggest an involvement of T cells in the pathogenesis of ANCA-associated vasculitis, the prophylactic value of therapy with low-dose cyclosporin was investigated in seven patients (three with Wegener's granulomatosis, four with microscopic polyangiitis, all with renal involvement) who had developed at least one relapse during cyclophosphamide (CP) treatment or in the first 4 months after the end of CP therapy. METHODS: After remission had been achieved for 6 months using CP and prednisolone, the CP dose was reduced (3 months 75%, 3 months 50%) and cyclosporin was added concomitantly (dose adjusted to whole blood levels 60-90 ng/ml). Cyclosporin therapy was continued for 1 year after the end of CP treatment. RESULTS: During a mean follow-up of 24 months no patient developed a relapse. Two patients developed a herpes zoster infection. No severe bacterial infection occurred. CONCLUSIONS: These preliminary results indicate that cyclosporin can be successfully used to sustain remission in patients with a relapsing course of ANCA-associated vasculitis and renal involvement.

Adult↗
PubMed1998

Reduced gonadal toxicity after i.v. cyclophosphamide administration in patients with nonmalignant diseases.

BACKGROUND: Cyclophosphamide has been used increasingly to treat patients with nonmalignant diseases like primary glomerulonephritis and systemic vasculitis. Thus long-term side effects like gonadal toxicity have become an important issue. Monthly i.v. cyclophosphamide pulse administration leads to a reduction in total dose of 60% compared to daily oral treatment which would be favorable for i.v. therapy. However, the risk of increased germinal damage due to higher peak levels had to be excluded. METHODS: Gonadal toxicity after different modes of cyclophosphamide administration was investigated in men with vasculitis or minimal change glomerulonephritis by measurement of FSH (follicle-stimulating hormone) plasma levels, as well as in Lewis rats by the investigation of testis histology and number of foetuses after mating with healthy female rats. RESULTS: FSH plasma levels after 3 months of treatment were significantly higher in men receiving daily oral cyclophosphamide (28.7 +/- 34 IU/l) compared to i.v. pulse administration (9.5 +/- 5.1 IU/l; p < 0.01) indicating a higher gonadal toxicity after oral treatment. In Lewis rats daily oral gavage led to a significantly reduced number of foetuses and changes in testis histology compared to pulse administration. CONCLUSION: As pulse administration of cyclophosphamide led to a significantly reduced gonadal toxicity compared to oral treatment this administration should be preferred, provided that an equal disease control and relapse rate is achieved.

Administration, Oral↗
PubMed1997

Renal transplantation for patients with autoimmune diseases: single-center experience with 42 patients.

BACKGROUND: In patients with autoimmune diseases such as vasculitis or systemic lupus erythematosus (SLE), end-stage renal disease develops in a high percentage of patients, and kidney transplantation has become a therapeutic option. However, only limited data about the prognosis and outcome after kidney transplantation are available. METHODS: Long-term graft survival and graft function of renal transplant recipients with SLE, Wegener's granulomatosis, microscopic polyangiitis, Goodpasture's syndrome, and Henoch-Schonlein purpura were evaluated in a single center. In addition, the incidence of renal and extrarenal relapses and the impact of the immunosuppressive therapy on the course of the autoimmune disease were studied. RESULTS: Renal transplant recipients with autoimmune diseases such as vasculitis and SLE had a patient survival rate (94% after 5 years) and a graft survival rate (65% after 5 years) comparable to those of patients with other causes of end-stage renal disease (patient survival 88% and graft survival 71% after 5 years). Graft losses due to the underlying disease were rare. Extrarenal relapses occurred in three patients with Wegener's granulomatosis, one patient with microscopic polyangiitis, and three patients with SLE, but were less frequent compared with the period with chronic dialysis therapy. Autoantibody levels in patients with SLE, Wegener's granulomatosis, or microscopic polyangiitis did not seem to influence the outcome. CONCLUSIONS: Renal transplantation should be offered to patients with autoimmune diseases. Follow-up should include the short-term control of renal and extrarenal disease activity.

Adult↗
PubMed1997

Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection.

OBJECTIVE: To investigate whether the determination of serum procalcitonin (PCT) in systemic autoimmune disease will help to discriminate invasive infection from highly active underlying disease. METHODS: Three hundred ninety-seven serum samples, from 18 patients with systemic lupus erythematosus (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV), were analyzed. Clinical disease activity was assessed by the Systemic Lupus Activity Measure in SLE patients and by the Birmingham Vasculitis Activity Score in AAV patients. Procalcitonin concentrations were determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP). Additionally, serum creatinine values were obtained. RESULTS: In 321 of the 324 samples from the 42 patients with autoimmune disease but without systemic infection, serum PCT levels were within the normal range (i.e., <0.5 ng/ml), whereas the values for neopterin, IL-6, and CRP were elevated in patients with active underlying disease. All 16 systemic infections occurred in 11 patients with AAV, and were associated with PCT levels that were markedly elevated, to a mean +/- SD of 1.93 +/- 1.19 ng/ml. No correlation between the degree of renal impairment and PCT concentrations was seen. CONCLUSION: PCT may serve as a useful marker for the detection of systemic bacterial infection in patients with systemic autoimmune disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Complexed plasma elastase as an in vivo marker for leukocyte activation in antineutrophil cytoplasmic antibody-associated vasculitis.

OBJECTIVE: It has been postulated that antineutrophil cytoplasmic antibody (ANCA)-induced degranulation of primed granulocytes and monocytes is involved in the pathogenesis of ANCA-associated vasculitis. Since elastase is the major lysosomal protein released during leukocyte degranulation, we investigated cell activation in vivo in patients with ANCA-associated vasculitis by determining complexed plasma elastase levels. METHODS: Plasma elastase complexed with alpha1-antitrypsin was measured in 20 patients with ANCA-associated vasculitis, using an immunoactivation assay. In parallel, C-reactive protein (CRP) and ANCA levels were determined and clinical disease activity was assessed. RESULTS: Complexed elastase levels were significantly elevated in patients with ANCA-associated vasculitis who had not received immunosuppressive therapy (mean +/- SD 71.5 +/- 22.6 microg/liter), compared with healthy volunteers (12.2 +/- 11.4 microg/liter; P < 0.001). Elastase decreased significantly after 2 weeks (46.5 +/- 26.8 microg/liter; P < 0.01) and further after 8-10 weeks of immunosuppressive treatment (28.1 +/- 13.4 microg/liter; P < 0.02), in correlation with decreasing vasculitis activity. Concomitantly, ANCA titers and CRP levels decreased. CONCLUSION: These data support the theory that, by the release of lysosomal proteinases, leukocyte activation may be involved in the pathogenesis of ANCA-associated vasculitis. In addition, plasma elastase may be used as a marker for disease activity.

Adolescent↗
PubMed1996

Clinical experience with a new recombinant hepatitis-B vaccine in previous non-responders with chronic renal insufficiency.

Patients with renal insufficiency have an increased risk of hepatitis B infection and a high probability to develop a chronic course of this disease. After hepatitis B vaccination they are known to show a low rate of seroconversion. In the present study we assessed the efficacy of a new recombinant pre-S1 and pre-S2 containing hepatitis B vaccine in 17 non-responders (anti-HBs titer 0) and 4 low-responders (anti-HBs titer < or = 5 IU/ml) with chronic renal insufficiency (16 on chronic hemodialysis therapy and 5 without hemodialysis treatment). Seroconversion rate was 65% after the third and 71% after the fourth vaccination. Only minor side effects were seen. These results encourage to use the new vaccine in a larger number of patients with renal insufficiency.

Adult↗
PubMed1995

Impaired endotoxin-induced interleukin-1 beta secretion, not total production, of mononuclear cells from ESRD patients.

Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS-induced IL-1 beta production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1 beta secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1 beta production remained unchanged but IL-1 beta secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1 beta secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1 beta secretion (P < 0.01) but did not enhance total IL-1 beta production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNF alpha was different comparing the three study groups. We conclude that LPS-induced IL-1 beta secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1 beta, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1 beta secretion in the presence of unchanged total IL-1 beta production. We speculate that PGE2 could inactivate the IL-1 beta converting enzyme which is essential for processing and secretion of mature IL-1 beta.

Adult↗
PubMed1992

In vitro production of interleukin-1 from blood mononuclear cells of patients on chronic hemodialysis therapy.

A monocyte defect is thought to be involved in the impaired immune response in patients on regular hemodialysis therapy. As an indicator of cell function, we studied in vitro IL-1 beta production of mononuclear cells from hemodialysis patients in comparison to normal controls. Mononuclear cells were stimulated with endotoxin or Staphylococcus epidermidis in parallel with control incubations in tissue culture medium alone. Spontaneous as well as stimulated total IL-1 beta production (cell-associated plus extracellular) did not differ significantly in cells obtained from patients compared to those from normal controls. However, the relative amounts of IL-1 beta released into the cell supernatants were significantly reduced in mononuclear cells from hemodialysis patients when stimulated with endotoxin but not with Staphylococcus epidermidis. These data indicate a stimulus-dependent defect in the mechanism of IL-1 beta release. As IL-1 is necessary for T-cell activation this alteration in mononuclear cell function may play a role in the impaired cellular immunity observed in patients on chronic hemodialysis therapy.

Culture Media↗
PubMed1991

Cyclophosphamide pulse therapy in Wegener's granulomatosis.

Twenty-three patients with Wegener's granulomatosis, 15 with daily oral cyclophosphamide therapy and eight with intravenous cyclophosphamide pulse therapy, were studied retrospectively. All patients had involvement of the kidneys and systemic symptoms. Mean monthly cyclophosphamide dose was 1.0 g in the pulse group and 2.7 g in the daily treated group. In all patients remission could be achieved. During 207.5 months of daily oral therapy the following complications were observed: leukopenia, necessitating dose reduction in seven patients, severe infection in one patient, relapses in three patients. During 103 months of intravenous pulse therapy one patient developed leukopenia. No patient had a severe infection. Two relapses were seen. Our data suggest that cyclophosphamide pulse therapy is an effective treatment strategy in patients with Wegener's granulomatosis and kidney involvement. It offers the chance of bladder protection and marked total dose reduction, possibly decreasing the risk of malignancies.

Administration, Oral↗
PubMed1990

Increase of C-reactive protein serum values following haemodialysis.

In this study serum C-reactive protein values were measured to prove the induction of an acute-phase response during the haemodialysis procedure in end-stage renal disease patients. C-reactive protein values were measured with a sensitive enzyme-linked immunosorbent assay to detect values below the detection limit of standard assays. Predialysis C-reactive protein serum values in 17 patients on regular haemodialysis with cuprophan dialysers were greater than those of 18 normal controls (P less than 0.001). In the same group of haemodialysis patients serum C-reactive protein values 24 h after haemodialysis were significantly greater than predialysis values (P less than 0.001). These results suggest that acute-phase proteins are induced during haemodialysis, probably due to cytokine release during the haemodialysis procedure.

Adult↗
PubMed1990

Hemodialysis-associated induction of cytokines.

The interleukin hypothesis relates chronic pathology in long-term end-stage renal disease (ESRD) patients to repeated stimulation of mononuclear cell cytokine production during hemodialysis. In vitro experiments demonstrated different possible mechanisms involved in hemodialysis-associated cytokine induction: adherence of mononuclear cells to the dialyzer membrane; complement activation, and the passage of cytokine-inducing bacterial fragments from contaminated dialysate through the dialyzer membrane into the blood. Studies investigating mononuclear cells from ESRD patients ex vivo suggest that these cells become activated during hemodialysis with complement-activating membranes and that the type of dialyzer membrane may influence mononuclear cell cytokine production in response to endotoxin. According to biological assays, plasma levels of interleukin-1 but not interleukin-6 activity seem to be elevated in ESRD patients compared to normal subjects and may increase further during treatment depending on the choice of the dialyzer membrane. However, to date, partly due to insufficient assay sensitivity and circulating inhibitors, measurements of interleukin-1, interleukin-6 and tumor necrosis factor in plasma by specific immunoassays could not finally prove elevated plasma cytokine levels in ESRD patients. Since circulating mononuclear cells are a major source of cytokines, studying the activation of these cells ex vivo seems to be the best approach to study hemodialysis-associated cytokine induction.

Cytokines↗
PubMed1990

Continuous arteriovenous hemofiltration: in vivo functional characteristics and its dependence on vascular access and filter design.

The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1988

Complement activation in patients with renal failure as detected through the quantitation of fragments of the complement proteins C3, C5, and factor B.

Using sensitive and highly specific enzyme-linked immunosorbent assays fragments of the complement proteins C3, C5, and factor B were quantitated in patients with renal failure. During hemodialysis on new cuprophan membranes raised levels not only of C3a, but in addition of activated C3, C5a, and Ba were demonstrated. In patients with chronic renal failure and end-stage renal disease plasma concentrations of Ba and activated C3 were markedly elevated independent of hemodialysis. This finding is taken as an indication of a continuous recruitment of the alternative pathway of complement in these patients. As the detected complement protein fragments are known to exert immune regulatory functions these findings may imply that these peptides are involved in the maintenance of the immune suppressed state in renal failure.

Acute Kidney Injury↗
PubMedDate not supplied

Chronic induction of C-reactive protein by hemodialysis, but not by peritoneal dialysis therapy.

OBJECTIVE: Evaluation of the inflammatory activity in patients on chronic peritoneal dialysis (PD) and patients on chronic hemodialysis (HD) in comparison to patients with chronic renal insufficiency without dialysis treatment and healthy volunteers. DESIGN: Open, nonrandomized prospective study. SETTING: Nephrology Department, including HD and PD therapy in a university hospital. PATIENTS: Twenty-four patients on chronic PD,21 patients on chronic HD therapy using a cuprophan dialyzer,16 patients with chronic renal insufficiency without dialysis treatment, and 33 healthy volunteers; 8 additional patients before and after initiation of chronic HD therapy. All patients and controls were without infection or immunosuppressive therapy. MAIN OUTCOME MEASURES: As a marker of the inflammatory activity in the different patient groups, C-reactive protein (CRP) was measured serially using a sensitive, enzyme-linked, immunosorbent assay in order to detect values below the detection limit of standard assays. RESULTS: Patient groups had CRP levels higher than the normal controls (p < 0.01). Patients on HD had CRP levels significantly higher than PD patients (p < 0.01) whose levels were comparable to patients without dialysis therapy. Accordingly, longitudinal measurements before and after initiation of chronic HD showed a significant increase in CRP levels after the beginning of HD treatment (p < 0.04). CONCLUSIONS: The results suggest that induction of the inflammatory activity is lower during PD compared to HD, since stimulation by the dialyzer membrane, dialysate buffer, or bacterial fragments in the dialysate is avoided. This observation might indicate a possible lower risk of long-term complications in patients with PD.

Acute-Phase Reaction↗