Biomedical subjects
J L Vanherweghem
Publications and source records attributed to J L Vanherweghem.
[Evidence-based medicine and art of healing: the dead end of incommensurate paradigms].
What is called the art of healing may refer to mainstream Western medicine (MM) as well as complementary and alternative medicines (CAM). MM asserts to be based on scientific evidence. The analysis of medical thought and practices in Evidence-Based Medicine (EBM) allows us to identify at least three paradigms on which MM is based: materialism (the rules of life are the rules of the natural sciences), reductionism (human diseases are diseases of the molecules) and neo-positivism (theories, diagnoses and treatments must be based on evidence). As in a mirror, CAM refer to the opposite paradigms of vitalism (life is the result of non measurable energies), holism (a whole human being cannot be fully understood from his/her parts) and relativism (there is no absolute reality nor truth, "facts are artifacts"). MM and CAM are thus based on diametrically opposed paradigms and the aim of an "integrative medicine" is aforetic. The problem is that CAM are very popular. The "art of healing" has to meet the expectations of patients wanting their illness taken into account while EBM often fails to identify a disease. EBM is thus faced with an ethical dead-end: patients must be relieved, using information based solely on scientific evidence and at the same time the use of placebo, unbeknown to them, must be rejected for ethical reasons. A solution might be found in a parallel coexistence but not in an integration, of EBM and CAM. Coexistence however does not mean coresponsibility.
Renal interstitial fibrosis and urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi).
A new renal disease called 'Chinese-herb nephropathy' (CHN) has been reported to occur in women who have ingested slimming pills containing powdered extracts of the Chinese herb Stephania tetrandra (ST). Moderate to end-stage renal disease developed, requiring renal replacement therapy by dialysis or transplantation. Phytochemical analyses of the pills revealed the presence of aristolochic acids (AA) instead of tetrandrine, suggesting the substitution of ST (Han fang ji) by Aristolochia fangchi containing nephrotoxic and carcinogenic AA. A typical histological feature of CHN is a progressive interstitial fibrosis leading to a severe atrophy of the proximal tubules, as documented by the urinary excretion rates of markers of tubular integrity (reduction of neutral endopeptidase enzymuria and high levels of microproteinurias). Removal of the native kidneys and ureters in end-stage CHN patients provided a high prevalence of urothelial carcinoma (46%). Tissue samples contained AA-related DNA adducts, which are not only specific markers of prior exposure to AA but are also directly involved in tumorigenesis. Exposure to Aristolochia species (spp.) is associated with the development of renal interstitial fibrosis (CHN) and urothelial cancer in humans. Health professionals should be aware that in traditional Chinese medicine, Aristolochia spp. are considered interchangeable with certain other herbal ingredients and are also sometimes mistaken for ST, Akebia, Asarum, Clematis spp. and Cocculus spp. in herbal remedies.
[Erasme is 25 years old].
The opportunity of the 25th anniversary of the Erasme hospital was taken for drawing up an inventory of the scientific publications issued from the medical teams of the institution. The inventory was established in accordance with the missions of an academic hospital, namely, evaluation and development of new diagnostic and therapeutic tools, creation of new knowledge in basic science as well as in clinical research, translation of new biomedical findings to patient's care by the fruitful back and forth between the laboratory and the bedside and, finally, launching of new skills to be prepared for the medicine of the new millennium. The assessment is positive. However, the future is uncertain due to the under reimbursement of the academic medicine.
[The medico-surgical department of nephrology dialysis and renal transplantation].
The Department of Nephrology of the Hospital Erasme, opened 25 years ago, is now performing, each year, 22,000 hemodialysis sessions, 800 patient-weeks of peritoneal dialysis treatment and 70 renal grafts. Scientific contributions of the department deal with vascular access for hemodialysis, susceptibility to infections of dialyzed patients, parathyroid surgery, biocompatibility of dialysis membranes, predictive factors of renal graft survival, immunosuppression with monoclonal antibodies, experimental studies of graft tolerance and rejection, toxic nephropathies. The most original contributions are related to anaphylactoïd reactions in hemodialysis by association of acrylonitrile membranes with inhibition of the converting enzyme, to advantages and side effects of OKT3 monoclonal antibody and to discovery and study of the Chinese herbs nephropathy.
Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi)
BACKGROUND: Chinese-herb nephropathy is a progressive form of renal fibrosis that develops in some patients who take weight-reducing pills containing Chinese herbs. Because of a manufacturing error, one of the herbs in these pills (Stephania tetrandra) was inadvertently replaced by Aristolochia fangchi, which is nephrotoxic and carcinogenic. METHODS: The diagnosis of a neoplastic lesion in the native urinary tract of a renal-transplant recipient who had Chinese-herb nephropathy prompted us to propose regular cystoscopic examinations and the prophylactic removal of the native kidneys and ureters in all our patients with end-stage Chinese-herb nephropathy who were being treated with either transplantation or dialysis. Surgical specimens were examined histologically and analyzed for the presence of DNA adducts formed by aristolochic acid. All prescriptions written for Chinese-herb weight-reducing compounds during the period of exposure (1990 to 1992) in these patients were obtained, and the cumulative doses were calculated. RESULTS: Among 39 patients who agreed to undergo prophylactic surgery, there were 18 cases of urothelial carcinoma (prevalence, 46 percent; 95 percent confidence interval, 29 to 62 percent): 17 cases of carcinoma of the ureter, renal pelvis, or both and 1 papillary bladder tumor. Nineteen of the remaining patients had mild-to-moderate urothelial dysplasia, and two had normal urothelium. All tissue samples analyzed contained aristolochic acid-related DNA adducts. The cumulative dose of aristolochia was a significant risk factor for urothelial carcinoma, with total doses of more than 200 g associated with a higher risk of urothelial carcinoma. CONCLUSIONS: The prevalence of urothelial carcinoma among patients with end-stage Chinese-herb nephropathy (caused by aristolochia species) is a high.
Nephropathy and herbal medicine.
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Role of complement and platelet-activating factor in the stimulation of phagocytosis and reactive oxygen species production during haemodialysis.
BACKGROUND: Neutrophil phagocytic functions have been studied extensively in haemodialysis (HD) patients; however, results are contradictory and the mechanisms that modulate phagocytosis and oxidative burst during dialysis are not completely understood. METHODS: The present study investigated neutrophil functions in a selected population of patients before and during clinical dialysis with cuprophane, and polyacrylonitrile (AN69) membranes. We measured phagocytosis of Escherichia coli and intracellular hydrogen peroxide (H2O2) production by flow cytometry in whole blood. RESULTS: Before dialysis, neutrophils from HD patients showed normal phagocytic capability and H2O2 formation. Phagocytosis of FITC-E. coli was significantly stimulated in cuprophane but not AN69-treated patients. Spontaneous and stimulated H2O2 production was enhanced with both cuprophane and AN69 membranes. We then investigated in vitro the role of complement and platelet-activating factor (PAF) in the activation of neutrophils. Incubation of whole blood with C5a increased phagocytosis but not H2O2 production. On the contrary, the addition of synthetic PAF showed a markedly stimulated H2O2 production without increase in phagocytosis. Moreover, during dialysis with formaldehyde-reused cuprophane, complement activation was abolished and phagocytosis was no longer enhanced, while the stimulation of H2O2 production persisted. In addition, we also excluded a particular role of the membrane itself in the activation of neutrophils. CONCLUSION: We demonstrated that in a selected population of HD patients, neutrophils exhibit normal phagocytic capability and normal intracellular H2O2 production. During dialysis, the stimulation of phagocytosis observed with cuprophane is complement dependent, whereas the enhanced H2O2 production observed with both cuprophane and AN69 membranes might be related to PAF production.
Comparison of cellulose diacetate and polysulfone membranes in the outcome of acute renal failure. A prospective randomized study.
BACKGROUND: Whether the nature of haemodialysis (HD) membranes can influence the outcome of acute renal failure (ARF) remains debatable. Recent studies have suggested that dialysis with bioincompatible unsubstituted cellulosic membranes is associated with a less favourable patient outcome than dialysis with biocompatible synthetic membranes. Since we generally use a modified cellulosic membrane with substantially lower complement- and leukocyte-activating potential than cuprophane, for dialysis of patients with ARF, and because there are no data in the literature regarding the influence of modified cellulosic membranes on the outcome of patients with ARF, we compared the outcome of ARF patients dialysed either with cellulose diacetate or with a synthetic polysulfone membrane. We also investigated the potential role of permeability by comparing membranes with high-flux versus low-flux characteristics. METHODS: This prospective, randomized, single centre study included 159 patients with ARF requiring HD. Patients were stratified according to age, gender, and APACHE II score and then randomized in chronological order to one of three dialysis membranes: low-flux polysulfone, high-flux polysulfone and meltspun cellulose diacetate. RESULTS: Aetiologies of ARF and the prevalence of oliguria were similarly distributed among the three groups. There was no significant difference between the three groups for survival (multivariate Cox's proportional hazards model, P=0.57), time necessary to recover renal function (P=0.82), and number of dialysis sessions required before recovery (P=0.86). Multivariate analysis showed that survival was significantly influenced only by the severity of the disease state (APACHE III score, P<0.0001), but not by the nature of the dialysis membrane (P=0.57) or the presence of oliguria (P=0.24). CONCLUSIONS: Among patients with ARF requiring HD survival and recovery time are not significantly influenced by the use of either meltspun cellulose diacetate or the more biocompatible high-flux or low-flux polysulfone. Dialysis using modified cellulose membranes is just as effective as dialysis using synthetic polysulfone membranes, but at a lower cost. In addition, the flux of the membrane did not influence patient outcome.
[Herbal remedies and nephrotoxicity].
Numerous substances from vegetal origin used as herbal remedies can be nephrotoxic. This article summarizes several circumstances of development of acute or chronic renal failure in which the responsible agent has been identified after a thorough toxicologic study. The Chinese herbs nephropathy is extensively described, detailing not only the epidemiological and histological aspects but also the extrarenal and neoplastic complications recently reported.
Efficacy of oral immunotherapy on respiratory infections in hemodialysis patients: a double-blind, placebo-controlled study.
BACKGROUND: Hemodialysis (HD) patients suffer from several immune defects that make them prone to develop bacterial infections, in particular respiratory tract infections (RTIs). PATIENTS AND METHODS: As previous studies have shown that oral immunotherapy with an immunomodulating bacterial extract (IBE) is effective against RTIs, we decided to test its efficacy and safety in HD patients during a double-blind placebo-controlled prospective study. 40 HD patients with a documented history of RTIs in the previous year were treated for 24 weeks of the endemic season with one capsule daily of IBE (n = 21) or placebo (PL, n = 19). Clinical examinations, measurements of Mac-1 and gp150.95 on circulating phagocytes and routine laboratory evaluations were performed at week 0, 4, 12 and 24. Patients were also examined at each dialysis session allowing an accurate recording of any infectious episode, its treatment and of any untoward effect. RESULTS: During the last period of the study (weeks 13-24), IBE significantly reduced the number of patients with RTIs and consequently of antibiotic treatment courses as compared to PL (p = 0.018), whereas no difference was detected between IBE and PL during periods I (weeks 0-4) and II (weeks 5-12). There was no difference between IBE and PL for other, non respiratory infections. IBE was associated at several time points with an increased expression on phagocytes of adhesion molecules involved in phagocytosis (Mac-1 and gp150.95). However, the expression of these molecules was not predictive for the occurrence of RTI. IBE was on the whole as well tolerated as PL, 7 patients presented side effects (5 IBE, 2 PL, NS) which led to drop-out in 4 cases (3 IBE, 1 PL). No serious side effect was recorded, gastrointestinal upset being the most prevalent type. CONCLUSION: The results of this study indicate that immunomodulation with selected bacterial extracts constitutes a promising approach for the prevention of bacterial airway infections in groups at risk, such as HD patients.
[Apocalypse 2000: the end of science and the golden age of pseudo-medicine].
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The policy of admission to the education in medicine and dentistry in the French-speaking community of Belgium.
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[Does the biocompatibility of the hemodialysis membrane influence the prognosis of acute renal insufficiency?].
Several recent publications have suggested that the use of cuprophane in the setting of acute renal failure is associated with a higher mortality (especially from sepsis) and a slower recovery of renal function in the survivors in comparison with more biocompatible membranes. We present here a critical review of these publications and point to several methodological bias that might invalidate their conclusions. However, while waiting further information, we would advocate to abandon the use of cuprophane to dialyze patients with acute renal failure.
Aristolochia sp and chronic interstitial nephropathies in Indians.
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Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.
Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.
Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis: a pilot study in Chinese herbs nephropathy.
Chinese herbs nephropathy is characterized by an extensive interstitial fibrosis and by a rapid evolution to end-stage renal failure. We thus decided to try steroid therapy (prednisolone 1 mg/kg for 1 month, tapered off 0.1 mg/kg every 2 weeks) in cases with moderate renal failure and evidence of deterioration in renal function. Our steroid group (SG) consisted of 12 female patients with biopsy-proven renal fibrosis who were followed for at least 12 months after the initiation of steroids. Plasma creatinine level (Pcreat) ranged from 1.8 to 3.9 mg/dL (mean +/- SEM, 2.8 +/- 0.2 mg/dL) when steroids were initiated at t = 0. Renal failure was in progression since Pcreat was 2.1 +/- 0.1 mg/dL (P = 0.022) 3 months before t = 0. Our control group (CG; N = 23) was selected retrospectively from among the 81 patients in the Belgian Register of Chinese Herbs Nephropathy. Compared with the CG, renal function was better preserved in the SG (Pcreat; mean +/- SEM): SG v CG, 2.9 +/- 0.3 mg/dL v 5.3 +/- 0.5 mg/dL at 6 months (P = 0.0024) and 4.0 +/- 0.7 mg/dL v 7.1 +/- 0.5 mg/dL at 1 year (P = 0.001). The slope of the reciprocal serum creatinine concentration was similar in both groups before t = 0 (-0.0463 mg/dL/mo in the SG v -0.0438 mg/dL/mo in the CG; P = 0.83), but it became less steep after initiation of steroid therapy (between 0 and 6 months, -0.000742 mg/dL/mo in the SG v -0.0284 mg/dL/mo in the CG; P < 0.001). Finally, only two of the 12 patients in the SG required dialysis at 1 year compared with 16 of the 23 patients in the CG (P = 0.0045). We conclude that steroid therapy slows the progression of renal failure in a disease characterized by an interstitial fibrosis that progresses quickly despite the fact that the insulting agent has been withdrawn. This supports the hypothesis that renal interstitial fibrosis may be an immune-mediated process.
OKT3 prophylaxis in renal grafts with prolonged cold ischemia times: association with improvement in long-term survival.
The data on patients participating in two randomized, prospective studies with similar immunosuppressive regimens were updated and combined to evaluate the long-term effects of OKT3 according to cold ischemia time (< or = or > 24 hr). Among 159 patients in the OKT3 and 153 in the cyclosporine A (CsA) group, 8 and 12 deaths occurred, respectively (P = NS). In patients with cold ischemia > 24 hours, OKT3 prophylaxis resulted in a lower mean number of rejection episodes per patient than did CsA prophylaxis within one year (mean +/- SEM: 0.87 +/- 0.11 vs. 1.35 +/- 0.14, respectively; P = 0.008) and within five years (1.07 +/- 0.12 vs. 1.49 +/- 0.15, respectively; P = 0.032). In contrast, rejection incidences in patients with cold ischemia < or = 24 hours was not significantly different in the two groups. In all study patients, there was a trend towards higher graft survival rates in the OKT3 group versus the CsA group (at 5 years, 73% vs. 66%, respectively; P = 0.182). Among recipients of kidneys with cold ischemia times > 24 hours, OKT3 patients had significantly higher graft survival than CsA patients at two years (84% vs. 64%, respectively) and at five years (71% vs. 56%, respectively; P = 0.045). Significant differences were not observed in recipients of kidneys with cold ischemia times < or = 24 hours. In conclusion, patients receiving renal grafts with long cold ischemia times strongly benefit from OKT3 prophylaxis.