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Biomedical subjects

R Brunkhorst

Publications and source records attributed to R Brunkhorst.

At least 37 records · Page 2Linked to original sources
PubMed1998

Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study.

OBJECTIVE: There is growing concern about the toxic side effects of daily oral cyclophosphamide (CYC) treatment. Intravenous (i.v.) pulse administration of CYC has been shown to be effective in patients with systemic lupus erythematosus, but contradictory results have been reported in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. METHODS: The efficacy and toxicity of i.v. pulse administration of CYC (0.75 gm/m2) versus daily oral CYC treatment (2 mg/kg body weight) were investigated in a prospective, randomized, multicenter study in patients with ANCA-associated vasculitis and renal involvement. RESULTS: The cumulative CYC dose was reduced by 57% in patients with i.v. pulse treatment (n = 22) compared with patients treated with daily oral therapy (n = 25). Patient survival, remission rate, time of remission, relapse rate, and outcome of renal function were not different between the 2 treatment groups. However, the rate of leukopenia (P < 0.01) and severe infections (P < 0.05 by 1-tailed test) was significantly reduced in the i.v. pulse group compared with the group receiving daily oral treatment. Moreover, gonadal toxicity was reduced in the i.v. pulse group, as indicated by significantly lower levels of follicle-stimulating hormone. CONCLUSION: This randomized study shows that i.v. CYC administration is an effective therapeutic tool with low toxicity in patients with ANCA-associated vasculitis and renal involvement.

Administration, Oral↗
PubMed1998

Pronounced renal vasoconstriction and systemic hypertension in renal transplant patients treated with cyclosporin A versus FK 506.

This prospective study investigated hypertension and renal vasoconstriction developing during the 1st year after renal transplantation in patients randomly allocated to treatment with FK 506 (n = 28) or CyA (n = 13). Starting doses were 0.2-0.3 mg/kg per day for FK 506 and 5-8 mg/kg per day for CyA: doses were subsequently adjusted to trough levels (5-15 ng/ml for FK 506 and 100-150 ng/ml for CyA). We compared 24-h ambulatory blood pressure measurement, antihypertensive treatment, serum creatinine, and resistance index (RI), measured by Doppler ultrasound at the level of the interlobar artery. Until month 2 of treatment, FK 506-treated patients had a significantly lower RI (8%) and better renal graft function, as evidenced by significantly lower serum creatinine values. Some 13% of FK 506-treated patients, compared to 70% of CyA-treated patients (P < 0.01), needed additional antihypertensive drugs after transplantation to keep blood pressure stable. FK 506 treatment, at the above-mentioned dosages, was associated with a significantly higher number of infections (urinary tract infection, pyelonephritis, and pneumonia). We conclude that CyA produces greater renal vasoconstriction and systemic hypertension than FK 506, as reflected in higher renal interlobar artery RI values and a greater need for antihypertensive treatment. After 2 months of treatment and a reduction in CyA trough levels, the renal effects (i.e., lower RI and lower creatinine values), but not the systemic hypertensive effects, disappear.

Adult↗
PubMed1998

Effect of a silver device in preventing catheter-related infections in peritoneal dialysis patients: silver ring prophylaxis at the catheter exit study.

Catheter-related infections remain a significant cause of method failure in chronic peritoneal dialysis (PD) therapy. Given the increasing antibiotic resistance, such nonpharmacological strategies as local silver devices attract more interest. To establish whether a silver ring device (designed by Grosse-Siestrup in 1992) mounted onto the PD catheter and placed at the exit site at skin level is effective in preventing exit-site and other catheter-related infections, a prospective 12-month, multicenter, controlled study stratified by diabetes status was conducted. The study subjects were assessed by an extensive structured inventory, including a broad spectrum of control variables, such as age, body mass index (BMI), Staphylococcus aureus carrier status, catheter features, mode and quality of PD therapy, comorbidity, and psychosocial rehabilitation. Ten experienced German outpatient dialysis centers (seven adult, three pediatric) participated in the trial. All eligible patients (n=195) from the study area without catheter-related infections during the ascertainment period were included (incidental subjects undergoing PD therapy for at least 3 months). The main outcome measures were the occurrence of first exit-site infections (primary study end point), sinus tract/tunnel infection, and peritonitis. Ninety-seven patients were assigned to the silver ring and 98 patients to the control group. Baseline characteristics of age, sex, proportion of pediatric and incidental patients, S aureus carrier status, and other variables were similar in both groups. The incidence of infections in the silver ring group versus the control group was as follows: 23 of 97 versus 16 of 98 patients had exit-site infections, 12 of 97 versus 12 of 98 patients had sinus tract/tunnel infections, 16 of 97 versus 18 of 98 patients had peritonitis, respectively. Kaplan-Meier analysis for the probability of an infection-free interval showed no statistical difference (log-rank test) between the two groups. Displacement of the silver ring contributed to study termination in 6% of the study group patients, including two patients with catheter loss. Univariate analysis and multiple logistic regression identified younger age (<50 years), low serum albumin level (<35 g/L), number of previously placed PD catheters, short cuff-exit distance (<2 cm), and S aureus nasal carriage as risk factors for the development of exit-site infections. In conclusion, our study does not show any benefit of the silver ring in preventing catheter-related infections in PD patients. Thus, prevention of infection-related method failure in PD still has to rely on conventional antibiotic treatment strategies and less so on alternative methods.

Adult↗
PubMed1998

Peritoneal mononuclear cell differentiation and cytokine production in intermittent and continuous automated peritoneal dialysis.

The long period without dialysate exchanges in nightly intermittent peritoneal dialysis (NIPD; no peritoneal filling during the day) and continuous cyclic peritoneal dialysis (CCPD; peritoneal filling during the day) might lead to an improved repopulation and functional regeneration of peritoneal macrophages (PMOs). We investigated this issue in seven stable, noninfected CCPD patients and seven stable, noninfected NIPD patients. PMO differentiation and cytokine production were measured after automated peritoneal dialysis and after a 12- to 14-hour period without dialysate exchanges. PMO maturation was evaluated by antibody staining. The proportion of "young" monocytes (positive for 27E10 and RM3/1) was decreased, whereas the proportion of mature macrophages (positive for 25F9) was significantly increased after the exchange-free interval. No differences between NIPD and CCPD were observed. The cytokine response to lipopolysaccharide was significantly increased after the exchange-free interval in both NIPD and CCPD. The interleukin-1 receptor antagonist (IL-1Ra) content of PMO lysates significantly increased after the exchange-free interval in both groups, but no changes were found in dialysate and serum IL-1Ra. We conclude that the long daytime interval without dialysate exchanges allows for additional PMO differentiation. Furthermore, the potential for cytokine release, which is inhibited (possibly by dialysate effects) after automated peritoneal dialysis, is restored after a 12- to 14-hour interval without peritoneal dialysis exchanges. The "dry" day in NIPD seems to have no important additional positive effect compared with CCPD.

Adult↗
PubMed1998

Automated peritoneal dialysis with 'on-line'-prepared bicarbonate-buffered dialysate: technique and first clinical experiences.

BACKGROUND: Automated peritoneal dialysis (APD) has the possibility of increasing the dialysis efficacy by using higher fill volumes, frequent dialysate exchanges, and tidal techniques. It is then possible to treat patients adequately without residual renal function. The drawbacks of the required high amounts of dialysis solution of up to 30 litres per session are the high costs of lactate-based dialysate bags and difficulties for the patients in handling these bags. So far, bicarbonate-based peritoneal dialysate, which may be more biocompatible, is only available for CAPD in double-chamber bags. In APD this could be overcome by 'on-line' preparation of bicarbonate-buffered dialysate using advanced technologies originally designed for on-line preparation of substitution fluid for haemofiltration. METHODS: Four patients without residual renal function were treated with APD five times weekly in a crossover study design. Patients received standard lactate-based (35 mmol/l) treatment (25 litres per session each) in weeks 1 and 3. In week 2 on-line-produced bicarbonate-buffered (37 mmol/l) dialysate was used. This dialysate was prepared by an AK 100 Ultra haemodialysis machine. The machine was modified for adding glucose from a 50% concentrate to the desired concentration of 1.7%. Electrolytes, pH, pCO2, and dialysis efficacy parameters were measured. Microbiological testing was carefully performed. RESULTS: Creatinine clearances, Kt/V, and pCO2 did not vary between the different treatment phases, whereas the pH showed a distinct increase during the bicarbonate phase. Repeated determinations of endotoxins and culturing showed no contamination of the dialysate. The composition of the produced dialysate was reproducible with respect to pH, pCO2, sodium, calcium and bicarbonate, whereas the glucose concentration varied by +/- 20%. CONCLUSIONS: On-line preparation of PD fluid with the AK 100 Ultra is easy and safe to handle. APD with dialysate containing 37 mmol/l bicarbonate provides improved acid base balance and possibly improved biocompatibility, and may lead to a significant cost reduction. Further development in order to provide smaller machines and more precise ways of achieving a desired dialysate glucose concentration is necessary.

Adult↗
PubMed1998

Survival and vasculitis activity in patients with end-stage renal disease due to Wegener's granulomatosis.

BACKGROUND: In patients with end-stage renal disease (ESRD) due to Wegener's granulomatosis, a decrease in vasculitis activity after the development of ESRD, as described in other autoimmune diseases, has been postulated. However, up to now no data in a larger group of patients with Wegener's granulomatosis on chronic dialysis have been available. METHODS: We retrospectively analysed the clinical course of 35 patients with Wegener's granulomatosis and ESRD during chronic dialysis treatment. Diagnosis was based on clinical manifestation, antineutrophil cytoplasmic antibodies and/or histology. RESULTS: During a mean follow-up of 43 months (5-113 months), six patients died, three related to treatment toxicity. The patient survival rates (according to Kaplan-Meier calculation) were 93% after 2 years and 79% after 5 years. Twenty-nine relapses of Wegener's granulomatosis occurred in 17 patients (relapse rate 0.24/patient/year); 2/3 of the relapses were seen during treatment with steroids, 1/6 during cyclophosphamide therapy. The relapses were not related to the dialysis membrane used. Remission or partial remission could be achieved in 93% of the relapses. CONCLUSIONS: The survival of patients on chronic dialysis treatment due to Wegener's granulomatosis was comparable to that of other patient groups with ESRD. The relapse rate was not different from that of non-dialysed patients with Wegener's granulomatosis, and this finding underlines the need for a therapeutic strategy to maintain long-term remission in dialysis-dependent patients, too.

Adolescent↗
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↗
PubMed1998

Procalcitonin in the early phase after renal transplantation--will it add to diagnostic accuracy?

The determination of serum procalcitonin (PCT) was tested for its utility in detecting invasive bacterial infection and acute rejection during the first 6 wk after kidney transplantation. Fifty-seven kidney graft recipients were prospectively included in the study. In 13/57 patients, 16 episodes of acute biopsy-proven rejection occurred and were treated with high-dose steroids (n = 14) or with OKT3 (n = 2). Seventeen out of 57 patients experienced 19 invasive bacterial infections; 2/57 had partial graft necrosis due to malperfusion. Twenty-five out of 57 graft recipients experienced an uncomplicated postoperative course. A total of 116 samples were analyzed and the following data obtained: PCT, C-reactive protein (CRP), white blood cell (WBC) count, corresponding body temperature and serum creatinine. Procalcitonin values for patients with rejection did not differ significantly from those of the healthy transplant recipients (p = 0.47). In contrast, PCT was clearly elevated with invasive bacterial infection or partial graft necrosis (p < 0.01). OKT3 treatment of rejection led to a more than 10-fold increase in PCT. C-reactive protein, unlike PCT, was elevated to a variable extent in patients with graft rejection, though CRP values were significantly more elevated in patients with infection than in those with rejection (p < 0.01). The specifity for detection of invasive bacterial infection was 0.7 for PCT and 0.43 for CRP, whereas sensitivity was 0.87 for PCT and 1.0 for CRP. There was no correlation between PCT and serum creatinine (r = 0.06). Haemodialysis did not lower PCT serum concentrations. Procalcitonin values rose postoperatively to peak levels on the first and second days and mostly declined to normals within 1 wk. In conclusion PCT, not being influenced by acute kidney graft rejection but serving as a specific indicator of systemic bacterial infection, could help to discriminate between both types of inflammation.

Bacterial Infections↗