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Biomedical subjects

C A Stegeman

Publications and source records attributed to C A Stegeman.

At least 73 records · Page 4Linked to original sources
PubMed1997

Are angiotensin converting enzyme inhibitors superior to beta blockers in retarding progressive renal function decline?

We questioned the superiority of angiotensin converting enzyme (ACE) inhibitors to beta blocking drugs with regard to renal function outcome in patients with mild to moderate renal insufficiency and normal to moderately elevated blood pressure (BP). We therefore studied 89 patients in a prospective double-blind randomized trial comparing the effect of enalapril and atenolol on the slope of glomerular filtration rate (GFR). Mean baseline GFR was 53 +/- 20 ml/min, untreated BP 152 +/- 20 mm Hg systolic and 90 +/- 11 mm Hg diastolic and median proteinuria 0.6 g/24 hr (interquartile range 0.0 to 2.5). After a run-in period without antihypertensives, the test drug was titrated to lower diastolic BP to a predefined goal of 10 mm Hg below baseline and/or below 95 mm Hg. The median follow up was 3.9 years. Antihypertensive therapy resulted in a comparable decrease of BP in both study groups. Filtration fraction and proteinuria decreased in both groups. The slope of GFR over time was not different between both groups (-1.39 +/- 2.82 and -1.97 +/- 3.38 ml/min/year on atenolol and enalapril, respectively). In multiple regression analysis a higher baseline GFR, a greater decrease in GFR and in proteinuria during titration and a lower proteinuria during follow up were independently related to a better GFR slope. We conclude that the use of ACE inhibitors is not imperative in all patients with non-diabetic nephropathy.

Adolescent↗
PubMed1996

Trimethoprim-sulfamethoxazole (co-trimoxazole) for the prevention of relapses of Wegener's granulomatosis. Dutch Co-Trimoxazole Wegener Study Group.

BACKGROUND: Respiratory tract infections may trigger relapses in patients with Wegener's granulomatosis in remission. Uncontrolled data have suggested that treatment with trimethoprim-sulfamethoxazole (co-trimoxazole) may be beneficial. METHODS: We conducted a prospective, randomized, placebo-controlled study of the efficacy of co-trimoxazole (800 mg of sulfamethoxazole and 160 mg of trimethoprim) given twice daily for 24 months in preventing relapses in patients with Wegener's granulomatosis in remission during or after treatment with cyclophosphamide and prednisolone. Relapses and infections were assessed with predefined criteria based on clinical, laboratory, and histopathological findings. Patients were evaluated at least once every three months for signs of disease activity, compliance with the treatment regimen, side effects of the therapy, and evidence of infections. Titers of serum antineutrophil cytoplasmic antibodies were measured serially. RESULTS: Forty-one patients were assigned to receive co-trimoxazole, and 40 to receive placebo. In 8 of the 41 patients in the co-trimoxazole group (20 percent), the drug had to be stopped because of side effects. According to life-table analysis, 82 percent of the patients remained in remission at 24 months, as compared with 60 percent of the patients in the placebo group (relative risk of relapse, 0.40; 95 percent confidence interval, 0.17 to 0.98). There were fewer respiratory tract infections (P = 0.005) and non-respiratory tract infections (P = 0.05) in the co-trimoxazole group than in the placebo group. There were no significant differences in antineutrophil cytoplasmic antibody titers at any time. Proportional-hazards regression analysis identified treatment with co-trimoxazole as an independent factor associated with prolonged disease-free survival and a positive antineutrophil cytoplasmic antibody test at the start of treatment as a risk factor for relapse. CONCLUSIONS: Treatment with co-trimoxazole reduces the incidence of relapses in patients with Wegener's granulomatosis in remission.

Adult↗
PubMed1995

Determination of protein catabolic rate in patients on chronic intermittent hemodialysis: urea output measurements compared with dietary protein intake and with calculation of urea generation rate.

We assessed the agreement between different methods of determining protein catabolic rate (PCR) in hemodialysis patients and the possible influence of postdialysis urea rebound and the length of the interdialytic interval on the PCR determination. Protein catabolic rate derived from measured total urea output was compared with recorded daily protein intake (DPI) and calculated urea generation rate (G), calculated by the interdialytic increase in serum urea and an estimated urea distribution volume using either the Watson equation or 58% of postdialysis body weight, and by single-pool urea kinetic modelling. In 16 patients PCR derived from calculated G by fixed urea distribution volume showed a significant decrease with blood samples obtained 10 minutes after dialysis onward as compared with immediately after dialysis, leading to an approximately 6% decrease at 60 minutes. Protein catabolic rate values derived from blood samples taken 15 to 60 minutes after dialysis were not significantly different. Urea kinetic modelling led to a significant increase in calculated PCR with samples from 5 minutes after dialysis onward and a total increase by 11.5% at 60 minutes. Different methods for determining PCR were compared in 13 clinically stable outpatients treated with conventional hemodialysis on cellulose acetate membrane dialyzers during 1 week. The mean PCR calculated from measured total urea output was 61.3 g/24 hr (range, 43.7 to 83.2 g/24 hr). Assessment of DPI as compared with PCR calculated from measured total urea output was lower by 7.5% (95% confidence intervale [CI], 1.4 to 17.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1995

Decreased frequency of HLA-DR13DR6 in Wegener's granulomatosis.

The pathogenesis of Wegener's granulomatosis, microscopic polyangiitis and idiopathic rapidly progressive glomerulonephritis (RPGN) is still unclear; in vitro data support both humoral and cellular autoimmune mechanisms. An association of Wegener's granulomatosis with HLA antigens has been described, with conflicting results concerning the antigens involved. We have performed serological HLA typing of patients at two different laboratories within the Netherlands (N = 118 and N = 106,N respectively). A significant decrease in the frequency of HLA-DR13DR6 was present in both patient groups in comparison to controls (chi 2 = 21.9; corrected P value < 0.004 for both groups together). There were no differences in the distribution of HLA-antigens between patients with Wegener's granulomatosis and microscopic polyangiitis, between cANCA (cytoplasmic anti-neutrophil cytoplasmic antibodies) and pANCA (perinuclear ANCA, anti-MPO) positive patients, and between patients with and without relapsing disease.

Aged↗
PubMed1995

Activation of granulocytes by anti-neutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis: a predominant role for the IgG3 subclass of ANCA.

To study ANCA-induced granulocyte activation in relation to disease activity in Wegener's granulomatosis (WG), serum samples taken from patients with WG at the time of active (n = 17) and inactive (n = 17) disease were analysed for their capacity to activate primed normal donor granulocytes. Compared with control sera (n = 6), the capacity of IgG fractions from patients with WG to induce the respiratory burst was significantly higher (P < 0.0001). Furthermore, the capacity to induce the respiratory burst significantly correlated with ANCA titre (r = 0.499, P = 0.003). IgG fractions from patients with active extensive disease induced the respiratory burst significantly more strongly than IgG fractions from patients with limited disease (n = 7) (P < 0.01) or patients during disease remission (n = 17) (P < 0.001). As ANCA-induced neutrophil activation is Fc-dependent and different IgG subclasses are involved in the interaction with various Fc receptors from neutrophils, we assessed changes in ANCA titre, total IgG and IgG subclass distribution of ANCA during active disease and remission in relation to the neutrophil-activating capacity of ANCA. Changes in capacity to activate granulocytes were related neither to changes in titre nor to changes in levels of total IgG, IgG1, IgG3, or IgG4 subclass of ANCA. However, changes in capacity to induce the respiratory burst were significantly related to changes in the relative amount of the IgG3 subclass of ANCA (P < 0.001), and not to changes in the relative amount of IgG1 or IgG4 subclass of ANCA. These data suggest that the increase in neutrophil-activating capacity of ANCA from inactive to active disease is, at least in part, based on the relative increase of the IgG3 subclass of ANCA that occurs during active disease.

Adult↗
PubMed1995

Influence of ambient plasma noradrenaline on renal haemodynamics in type 1 (insulin-dependent) diabetic patients and healthy subjects.

Imbalances in renal vasodilatory and vasoconstrictive mechanisms are responsible for the renal haemodynamic changes observed in Type 1 diabetes mellitus. Animal experiments have shown that noradrenaline (NA) infusion increases the intraglomerular pressure by predominantly efferent arteriolar vasoconstriction. The relationships between ambient plasma NA levels and renal haemodynamics were studied in 18 healthy control subjects (group C); in 17 normoalbuminuric diabetic patients (group D1) (albumin excretion rate (Ualb V) < 20 micrograms min-1), and in 17 microalbuminuric Type 1 diabetic patients (group D2) (UalbV 20-200 micrograms min-1), all patients being without overt autonomic neuropathy. Supine glomerular filtration rate (GFR (ml min-1 1.73 m-2)) and effective renal plasma flow (ERPF (ml min-1 1.73 m-2)) were determined over a 2-h period using constant infusions of 125I-iothalamate and 131I-hippuran, respectively. The subjects were studied in the fasting state. The diabetic patients were investigated during near normoglycaemia. Data are given as means and SD. In group D1, GFR and ERPF (126 +/- 15 and 538 +/- 89, respectively) were elevated as compared with controls (108 +/- 15 and 478 +/- 73; p < 0.01 and p < 0.05, respectively). In group D2, GFR (124 +/- 25, p < 0.05) but not ERPF (515 +/- 104) was higher than in the controls. GFR and ERPF were negatively correlated with venous plasma NA in group C (r = -0.61, p < 0.005 and r = -0.64, p < 0.001, respectively), in group D1 (r = -0.54, p < 0.03 and r = -0.63, p < 0.005, respectively) and in group D2 (r = 0.53, p < 0.03 and r = -0.60, p < 0.01, respectively). Multiple regression analysis disclosed that diabetes per se, independent from plasma NA, had a positive contribution to GFR. In contrast, ERPF was only related to plasma NA levels. GFR and ERPF are inversely related to venous plasma NA levels, both in healthy and in diabetic subjects, supporting the hypothesis that plasma NA is a vasoconstrictive substance. The independent positive effect of diabetes as a categorial variable on GFR, suggests that concomitant vasodilating mechanisms play a role in the renal haemodynamic alterations in Type 1 diabetes mellitus.

Adult↗
PubMed1994

Association of chronic nasal carriage of Staphylococcus aureus and higher relapse rates in Wegener granulomatosis.

OBJECTIVE: To examine possible risk factors for relapse, including chronic nasal carriage of Staphylococcus aureus and serial antineutrophil cytoplasmic antibody (ANCA) determinations in patients with Wegener granulomatosis. DESIGN: Observational cohort study. SETTING: Outpatient clinic at a university-affiliated hospital. PATIENTS: Consecutive patients (n = 71) with biopsy-proven Wegener granulomatosis who were seen during follow-up at the outpatient clinic from January 1988 to July 1991. Fourteen patients were ineligible or dropped out; 57 patients were analyzed. MEASUREMENTS: Serial ANCA determinations and swab cultures of both anterior nares for S. aureus taken at each visit every 4 to 6 weeks. Occurrence of infections and relapses of Wegener granulomatosis were identified according to strict, predefined criteria. RESULTS: Thirty-six of the 57 patients (63%; 95% CI, 49% to 76%) were found to be chronic nasal carriers of S. aureus (> or = 75% of nasal cultures positive for S. aureus). Proportional-hazards regression analysis identified chronic nasal carriage of S. aureus (adjusted relative risk, 7.16; CI, 1.63 to 31.50), creatinine clearance above 60 mL.min-1 (adjusted relative risk, 2.94; CI, 1.27 to 6.67), and a history of previous relapses of Wegener granulomatosis (adjusted relative risk, 1.33; CI, 0.98 to 1.78) as independent risk factors for relapse. Twenty-two of 33 patients persistently or intermittently positive for ANCA had a relapse as opposed to only 1 of 21 persistently negative patients. Relapses of Wegener granulomatosis were not related to diagnosed infections. CONCLUSION: Chronic nasal carriage of S. aureus identifies a subgroup of patients with Wegener granulomatosis who are more prone to relapses of the disease, suggesting a role for S. aureus in its pathophysiology and a possible clue for treatment.

Adult↗
PubMed1994

Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E-selectin in patients with Wegener's granulomatosis. Relationship to disease activity and relevance during followup.

OBJECTIVE: To assess the value of measuring serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAMP-1), and soluble E-selectin for monitoring disease activity in Wegener's granulomatosis (WG). METHODS: A sandwich enzyme-linked immunosorbent assay was used to measure levels of soluble adhesion molecules at the time of diagnosis in 22 consecutive patients with WG, in 12 WG patients studied serially prior to disease relapse, at the time of upper airways infection in 18 patients with inactive WG, and in 57 controls. Disease activity was assessed by disease activity score and C-reactive protein levels. RESULTS: At diagnosis of WG, sICAM-1 and sVCAM-1 levels were significantly elevated and correlated with disease activity. At the time of relapse, a significant increase in all 3 soluble adhesion molecules was found compared with levels at 6 months prior to relapse, but only sVCAM-1 levels were significantly elevated compared with those in controls. Levels of soluble adhesion molecules at the time of relapse did not differ from those measured during an upper airways infection without disease activity. CONCLUSION: Elevated serum levels of sICAM-1 and sVCAM-1 can be found in active WG and correlate with disease activity. However, their clinical relevance for followup is limited due to lack of sensitivity and specificity for WG disease activity.

Adolescent↗
PubMed1994

GC-MS determination of ratios of stable-isotope labelled to natural urea using [13C15N2]urea for studying urea kinetics in serum and as a means to validate routine methods for the quantitative assay of urea in dialysate.

A GC-MS determination of urea in serum or spent dialysate is described, using 13C15N2-labelled urea and assaying the area ratio of labelled to natural urea by mass fragmentographic monitoring of fragments m/e 153 and 156, after its eventual conversion into the trimethylsilylether-derivative of 2-hydroxypyrimidine. The procedure can be successfully applied in the follow-up of the disappearance of labelled urea in serum after intravenous injection in man, enabling kinetic parameters of urea to be established, e.g. for purposes of studying the effectiveness of dialysis procedures. Furthermore the method can be used for validation of routine methods for measuring urea in other fluids, in particular dialysate. Examples are given of both applications of the GC-MS method described.

Calibration↗
PubMed1994

T cell reactivity to proteinase 3 and myeloperoxidase in patients with Wegener's granulomatosis (WG).

T cell-mediated immunity is hypothesized to play an important role in the pathogenesis of granulomatous inflammation and vasculitis as found in patients with WG. The antigenic specificities of those T cells remain, however, unknown. Anti-neutrophil cytoplasmic antibodies (ANCA) present in patients with WG are directed to proteinase 3 (PR3) and myeloperoxidase (MPO). In the present study we investigated the proliferative capacity of peripheral blood mononuclear cells (PBMC) from patients with WG and age- and sex-matched controls in response to the WG autoantigens PR3 and MPO. Possible mitogenic effects of active PR3 and toxic effects of active MPO were excluded by using heat-inactivated PR3 and MPO. Antigen-specific stimulation induced by these autoantigens was studied by using processed PR3 and MPO in the lymphocyte stimulation test (LST). Proliferation induced by processed antigen correlated with that by heat-inactivated free antigen. The general capacity to proliferate in response to mitogens and recall antigens did not differ between patients and controls. However, patients with WG who were or had been positive for PR3-ANCA (n = 17) responded more strongly to PR3 than to MPO and showed higher responses to PR3 compared with controls (n = 13). Within the PR3-ANCA group T cell proliferation did not correlate with ANCA titre. In a small group of patients with MPO-ANCA (n = 5) no differences were observed compared with controls for MPO-specific proliferation. The data presented demonstrate that autoreactive PR3-specific T cells are present in patients with WG. Their fine specificity and possible role in the pathogenesis of WG have to be defined in further studies.

Adult↗
PubMed1994

Late recurrence of Wegener's granulomatosis presenting as solitary upper lobe pulmonary mass.

Recurrent Wegener's granulomatosis (WG) was diagnosed in a 40 year old man presenting with a solitary mass in the right lung apex and with possible lymph node enlargement in the anterior mediastinum, resembling malignancy. Eight years previously, a first episode of WG involving the upper airways and kidneys, but not the lungs, had been successfully treated with prednisolone and cyclophosphamide, which could be stopped after 2 yrs. The antineutrophil cytoplasmic antibody titres (anti-protease 3), which had been very high during the first disease episode, failed to predict the recurrence.

Adult↗