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Y W Sijpkens

Publications and source records attributed to Y W Sijpkens.

14 recordsLinked to original sources
PubMed2001

Risk factors of cyclosporine nephrotoxicity after conversion from Sandimmune to Neoral.

BACKGROUND: In 1995 - 1996, we switched from a once-daily Sandimmune dose to a twice-daily dose regimen of Neoral. Concurrent with the switch we changed our target trough level from 100 microg/l at 24 hours to the generally accepted 12-hour level of 150 microg/l. We performed a retrospective cohort study to assess cyclosporine toxicity following this switch and to identify risk factors for nephrotoxicity. PATIENTS AND METHODS: Of 212 patients with a stable graft function pre-conversion clinical parameters at 1 and 12 months post-conversion were compared with those at time of conversion. Cyclosporine nephrotoxicity was defined as a significant decline of the reciprocal of the serum creatinine concentration over time post-conversion in the absence of other obvious causes for declining graft function. Risk factors of cyclosporine nephrotoxicity were assessed using logistic regression analysis. RESULTS: The mean cyclosporine trough level rose from 87 microg/l at the time of conversion to 139 microg/l at 12 months post-conversion whereas the daily drug dose increased over the same period from 233 mg to 252 mg. Mean serum creatinine increased by 10% from 135 to 148 micromol/l (p < 0.001). Cyclosporine nephrotoxicity was present in 42 patients (20%). Cyclosporine dose and trough level did not predict nephrotoxicity but beta-blockers (OR 0.35, 95% CI 0.17-0.72) and calcium channel blockers (OR 0.35, 95% CI 0.19-0.82) reduced the risk of nephrotoxicity, independent from an effect on blood pressure. CONCLUSION: 20% of stable renal transplant patients experienced chronic cyclosporine nephrotoxicity after conversion from a once-daily Sandimmune regimen to a twice-daily Neoral regimen with dose adjustments to a trough level of 150 microg/l. beta-blockers and calcium channel blockers reduced the risk of nephrotoxicity.

Adrenergic beta-Antagonists↗
PubMed2000

Morphometry of interstitial fibrosis.

Several clinical studies have confirmed that histomorphometric changes in the tubulointerstitial compartment contain the best correlating parameters to predict the development of progressive renal insufficiency. The process of interstitial fibrosis is accompanied by an influx of inflammatory cells, up-regulation of fibrogenic cytokines such as transforming growth factor-beta and basic fibroblast growth factor, transient down-modulation of their antagonists, generation and proliferation of myofibroblasts, and, finally, by accumulation of interstitial collagens and proteoglycans. A careful morphometric analysis of interstitial fibrosis requires sensitive parameters through which the severity can be quantified and by which the progression into renal insufficiency can be predicted. We have addressed these issues by morphometric analysis of both human biopsies and by refining existing experimental models in the rat. Morphometric analysis was performed using a Zeiss microscope equipped with a full colour 3CCD camera and KS-400 image analysis software from Zeiss-Kontron. For studies with human material, biopsies were examined from patients with various renal diseases including patients with chronic allotransplant dysfunction. The development of interstitial fibrosis was correlated with clinical parameters. In experimental models, we analysed the interstitial composition and eventual glomerular alterations in rats with bovine serum albumin (BSA)-induced protein overload nephropathy and with human IgG-induced chronic serum sickness nephritis. Finally, we adapted and refined the model of ureter obstruction-induced interstitial fibrosis in the rat. For this purpose, custom-made titanium clips (S&T, Neuhaus, Switzerland) were implanted around the ureter in the abdomen of rats to obstruct the ureter without causing necrosis. The clips were removed at various time points after obstruction of the ureter (1-14 days). The subsequent remodelling of the interstitium was studied thereafter, in order to establish whether uraemia-induced interstitial fibrosis remains reversible at all times. In rat models, we have found that both protein overload-induced and serum sickness-induced interstitial fibrosis are accompanied by the development of focal and segmental glomerulosclerosis. Only in the ureter obstruction model did selective interstitial fibrosis develop, and remained reversible at all times studied. For the reliable assessment of interstitial fibrosis we have found that the best correlating parameters of interstitial fibrosis with renal function were: (i) the ratio of protein accumulation of TGF-beta-1 and its antagonist decorin; (ii) interstitial expression of smooth muscle alpha-actin; and (iii) accumulation of interstitial collagens (as determined by immunoperoxidase and by Sirius red staining).

Animals↗
PubMed1999

Sharing cross-reactive groups of MHC class I improves long-term graft survival.

BACKGROUND: Renal transplant loss from chronic rejection remains substantial. To increase our understanding of this syndrome, we identified risk factors predicting late graft loss, with a special emphasis on the impact of human lymphocyte antigen (HLA) matching. METHODS: We studied all 654 cadaveric kidney transplants performed in our center between 1983 and 1996 that had survived for more than six months. Eighty-two transplants, lost because of chronic rejection, were used as the outcome variable. The influence of HLA mismatches and shares on long-term graft survival was evaluated at the level of private antigens and cross-reactive groups (CREG) of multiple histocompatibility complex (MHC) class I. HLA and other recipient, donors and transplant parameters were studied using univariate and multivariate Cox regression analysis. RESULTS: The cohort had a mean number of 1.9 HLA mismatches. Because of the homozygosity of HLA antigens, HLA mismatches were not reciprocal to shares. CREG and HLA-A-B mismatches had a relative risk for graft loss of 1.19 (95% CI, 0.97 to 1.45) and 1.05 (0.84 to 1.32) per mismatch. In contrast, the relative risk per shared CREG and broad HLA-A-B antigen was 0.76 (0.63 to 0.92) and 0.79 (0.61 to 1.03). Multivariate analysis revealed that individuals sharing less than four CREGs had a relative risk of 2.13 (1.29 to 3.75) for late graft loss. Other independent predictors were a recipient age of less than 50 years, relative risk 1.95 (1.02 to 3.71); a donor age of more than 50 years, relative risk 1.68 (1.01 to 2.80); acute rejection (vascular vs. no rejection), relative risk 3.52 (1.72 to 7.18); proteinuria (dipstick > 1+ vs. negative), relative risk 2.86 (1.29 to 6.35); and a serum creatinine concentration of more than 150 micromol/liter at six months, relative risk 3.41 (1.96 to 5.94). CONCLUSION: We identified several coexisting recipient-, donor-, and transplant-related risk factors for graft loss from chronic rejection. In this well-matched group of renal transplants, HLA mismatches and shares had a nonreciprocal relationship. Sharing of HLA antigens, especially CREG of MHC class I, was associated with improved long-term survival.

Adult↗
PubMed1997

[Spondylodiscitis caused by Streptococcus agalactiae].

Two previously healthy adults, a man aged 69 and a woman aged 51 years, presented with spondylitis caused by Streptococcus agalactiae. One patient had fever and acute pain in the neck, the other progressive pain in the lower back. From cultures of blood and bone respectively. S. agalactiae was isolated. Both patients recovered after treatment with benzylpenicillin. S. agalactiae (group B streptococcus) is a wellknown cause of invasive infections in neonates and pregnant adults. Infections in nonpregnant adults are increasingly reported. Chronic conditions such as diabetes mellitus are strongly associated with disease caused by S. agalactiae.

Aged↗
PubMed1995

Enterococcus faecalis colonisation and endocarditis in five intensive care patients as late sequelae of selective decontamination.

OBJECTIVE: To describe Enterococcus faecalis colonisation and endocarditis in 5 intensive care patients after treatment with selective decontamination (SDD). SETTING: Intensive care unit (ICU) in a general hospital. PATIENTS: The patients were admitted to the ICU because of adult respiratory distress syndrome, polytrauma (2 patients), abdominal aortic surgery and gastrointestinal surgery. Because these patients needed mechanical ventilation they received systemic cefotaxime and SDD (polymyxin E, amphotericin B and norfloxacin). RESULTS: Colonisation with E. faecalis was documented in all patients. Intravascular catheter-related infection with E. faecalis occurred in 4 patients. None of the patients received antibiotics active against, E. faecalis, because body temperature normalised after catheter removal. In the course of his ICU stay one patient died. Autopsy showed E. faecalis endocarditis. The other 4 patients recovered from their primary illness, but had to be readmitted after several months because of E. faecalis endocarditis. One of these patients died. One patient recovered of endocarditis, but one year later valve surgery was necessary. The other 2 patients needed acute valve replacement. The latter 3 patients survived. CONCLUSION: We observed 5 patients with E. faecalis endocarditis as a late and severe sequela of SDD during their ICU stay.

Aged↗
PubMed1994

Unusual presentation of acquired toxoplasmosis in an immunocompetent adult.

We report an unusual clinical presentation of toxoplasmosis. Fever and headache were the only complaints of a 48-year-old immunocompetent man who was found to have a rash, hepatitis and a pericardial effusion. Lymphadenopathy was not present. Evolving atypical lymphocytosis was the clue to the diagnosis of toxoplasmosis. Undercooked meat was the probable source of infection.

Acute Disease↗