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Biomedical subjects

A Elewaut

Publications and source records attributed to A Elewaut.

At least 19 recordsLinked to original sources

Influence of low-dose oral contraceptives, alcohol, and grapefruit on.

The aminopryine breath test (ABT) measures hepatic reserve in patients with acute and chronic liver disease and gives an assesment of the hepatic function in patients undergoing major liver surgery. Aminopyrine is metabolized by the mixed cytochrome P-450 system, which can be influenced by many foreign compounds and drugs. Whether these foreign compounds and drugs can influence the results of the ABT has seldomly been tested. We studied three groups: Healthy female volunteers, either normally menstruating or taking oral contraceptives, were asked to perform a [13C]ABT during the time of the menses and at midcylce. Healthy volunteers were asked to perform a ABT after consuming 30 g of alcohol. Healthy volunteers were asked to perform a ABT after consuming 250 ml of grapefruit juice. The 13C/12C ratio in expired air was measured by gas isotope ratio mass spectrometry.

Acute Disease↗

Long term response to interferon treatment in chronic hepatitis C patients is associated with a significant reduction in anti-E1 envelope antibody titers.

Interferon (IFN) alfa has been used widely for the treatment of chronic hepatitis C virus (HCV) infections but only a small number of patients treated have shown a sustained biochemical and virological response. Anti-envelope E1 and E2 antibody titers were assessed retrospectively before, during, and after treatment with IFN in order to evaluate their usefulness for the prediction and monitoring of therapy outcome in 115 patients infected chronically with HCV genotype 1b. At baseline, E2 induced more frequent and stronger immunogenic responses than E1, irrespective of patient response to therapy. E1 and E2 antibodies also tended to be higher in patients with a long-term or a transient response to IFN treatment than in patients who were absolute non-responders. In most patients, E1 and E2 antibody levels tended to be lower after treatment. This reduction was most pronounced and occurred most frequently in long-term responders to therapy. In this patient group, the reduction of E1 antibodies was more pronounced than that of E2 antibodies. In contrast to E2 antibodies, the decrease of E1 antibodies could already be observed at the end of therapy (week 24) and was significantly larger (p<0.05) than that observed in relapsers and non-responders. Thus, a sustained elevation of E1 antibodies seems to be associated with ongoing infection even when HCV RNA levels were undetectable in serum. Monitoring of E1 antibody titers may represent a useful additional marker to discriminate sustained responders from those who relapse in patients receiving interferon therapy.

Antigens, Viral↗

Gallstone recurrence after successful shock wave therapy: the magnitude of the problem and the predictive factors.

OBJECTIVE: Reports concerning long term recurrence of gallstones after successful extracorporeal shock wave lithotripsy (ESWL) show a high probability of stone recurrence. There is still discussion on the factors influencing stone recurrence. In this study we wanted to evaluate the long term recurrence of gallstones after stone clearance with ESWL and oral bile acids, and to assess possible risk and preventive factors of stone recurrence. METHODS: A total of 322 consecutive patients with stone clearance between December 1988 and December 1995 were included. All patients were contacted for ultrasonography and were interviewed for additional information on daily intake of aspirin, NSAIDs, cholesterol lowering medication, estrogen therapy, and biliary pain during follow-up. RESULTS: A total of 187 patients were still stone-free after a mean follow-up of 35 months (range: 3-89 months); 135 patients had recurrence. There was a significant association between stone recurrence and estrogen intake (p = 0.04), number of lithotripsy sessions (p = 0.0007), time until stone disappearance (p = 0.0003), and biliary pain (p < 0.0001). There was no difference in recurrence rate between solitary and multiple stones. CONCLUSIONS: Long-term recurrence of gallstones after lithotripsy is high: < or = 69% after 6 yr. We found a significant association of stone recurrence with estrogen intake, number of lithotripsy sessions, and time until stone disappearance. Intake of aspirin or NSAIDs was not associated with decreased stone recurrence. Of the patients with recurrent stones, 57% had biliary pain.

Actuarial Analysis↗

Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients.

BACKGROUND/AIMS: In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pertreatment factors associated with response or non-response. METHODS: Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment. RESULTS: Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%,) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down-titration this difference in viral on-treatment response was lost. CONCLUSIONS: In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.

Adult↗

Ultrarapid hepatitis C virus clearance by daily high-dose interferon in non-responders to standard therapy.

BACKGROUND/AIMS: To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha, we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to standard treatment. METHODS: Eleven non-responders to previous therapy with 3-6 MU interferon three times a week were retreated with daily 10 MU. Plasma was sampled at days 0, 1, 2, 3, 14 and 28; all samples were prepared within 2 h and stored at -70 degrees C without thawing until analysis. The quantitative HCV RNA level was assessed by the Superquant assay (NGI, USA). The Eurohep reference panel, tested blindly, confirmed the linearity of the assay with a detection limit for genotypes 1 and 3 between 10(2) and 10(3) copies/ml. RESULTS: All patients showed a fall in viral load between week 0 and week 2 (2.6 log, i.e. 99.7%, range 1.3-4.7 log), whereas no fall was detected after week 2. Closer examination in nine patients revealed that all had a dramatic fall in the first 2 days (first day 1.8 log, 0.8-3.5; second day 0.8 log, -0.2-1.3), without any significant fall thereafter. The calculated half-life of viral decay in plasma was 5 (2-8.9) h, corresponding to a clearance of 2.4 (0.2-13.7) x 10(11) virions per day. Sustained responders showed a significantly greater fall in viral load in the first day (3.2 log, 2.8-3.5) than those who did not respond (1.4 log, 0.8-2.1, p=0.001). All three sustained responders had undetectable plasma HCV RNA at day 14. CONCLUSION: In patients without a response to standard interferon, the hepatitis C virus has a high daily turnover rate similar to that reported in naive patients. Our findings suggest that an early clearance of HCV RNA from the circulation is the key to a sustained response, which might be induced in about 25% of these patients by treatment with high (10 MU) daily doses of interferon. These findings have important implications for the concept of treatment of hepatitis C, which should shift its focus from long-term mild treatment towards aggressive therapy aiming at a fast viral disappearance within the first few days.

Adult↗

Constipation and other chronic gastrointestinal problems in spinal cord injury patients.

From a questionnaire sent to 90 spinal cord injury (SCI) patients it is concluded that 58% of patients with a complete SCI above L2 suffer from constipation, defined as two or fewer bowel movements per week, or the use of aids such as laxatives, manual evacuation or enemas. Tetraplegic patients had the highest prevalence of constipation, while patients with low paraplegia were less prone to constipation. The use of anticholinergic drugs was found to predispose to constipation. Preserved rectal sensation did not influence the presence of constipation. Faecal incontinence was rare. Regular abdominal pain was present in one third of SCI patients and might be caused by an irritable bowel syndrome in 62% of these.

Abdominal Pain↗

Hepatitis C virus genotypes: epidemiological and clinical associations. Benelux Study Group on Treatment of Chronic Hepatitis C.

In a cohort of 292 chronic hepatitis C patients living in the Benelux countries the relationship between viral genotype and geographical origin, route of transmission, clinical characteristics and severity of liver disease was analyzed. HCV-RNA isolates could be classified by the Line Probe Assay (LiPA) as 1a, 1b, 2, 3, 4 or 5 in 286 (98%) cases. Patients of European origin were predominantly infected with HCV subtype 1b (164/254, 65%, CI 58-70%), as were patients of Asian origin (7/13, 54%). Patients originating from Surinam (South America) had predominantly type 2 (9/10, 90%), whereas Africans were mainly infected with type 4 (7/9, 77%). Blood transfusion was the mode of transmission in 142 (50%) patients, intravenous drug abuse (IVDA) in 40 (14%), occupational needle accident or tattoo in 11 (4%); no obvious source of infection was found in 93 (33%). In patients infected by blood transfusion, subtype 1b was predominant (70%, CI 61-77%), whereas subtypes la and 3 were predominant in those infected by IVDA (25% and 45%, respectively, p<0.001). Cirrhosis was observed in 68 (24%) patients; in multivariate analysis, factors independently related to cirrhosis were: the duration of infection, age and prior hepatitis B. No significant relationship was found between the severity of fibrosis or liver inflammation and the HCV (sub)types. In summary, in this large cohort of patients in the Benelux countries the hepatitis C virus (sub)type present was clearly related to the country of origin and the route of transmission, but not to the severity of liver disease.

Adult↗

Diuretic requirements after therapeutic paracentesis in non-azotemic patients with cirrhosis. A randomized double-blind trial of spironolactone versus placebo.

BACKGROUND/AIMS: Diuretic requirements after mobilization of ascites by paracentesis have never been assessed in cirrhosis. It is also unknown whether diuretics increase the incidence of postparacentesis circulatory dysfunction. The aim of this study was to investigate these features and to assess whether measurement of plasma renin activity and aldosterone prior to paracentesis predicts diuretic response after this procedure. METHODS: Thirty-six patients with non-azotemic cirrhosis and ascites treated by total paracentesis plus i.v. albumin were randomly assigned to receive placebo (n=17) or spironolactone 225 mg/day (n=19) immediately after paracentesis and followed-up for 4 weeks. RESULTS: Five patients (three in the placebo and two in the spironolactone group) abandoned the treatment prior to ascites recurrence or the end of the study due to complications or lack of compliance. The analysis was performed in the remaining 31 patients. Ascites recurrence was more common in the placebo group (13 cases, 93%) than in the spironolactone group (3 cases, 18%) (p<0.0001) and occurred within the first 2 weeks of follow-up in more than 50% of patients. Patients developing ascites in the spironolactone group had higher levels of renin (14.1, 20.6, 32.4 ng/ml per h) and aldosterone (120, 149, 288 ng/dl) than those who did not develop ascites (renin: 2.0+/-2.1 ng/ml per h; range 0.1-6.8; aldosterone: 43+/-38 ng/dl; range 4-116). Three patients in the placebo group and two in the spironolactone group developed postparacentesis circulatory dysfunction (defined as an increase in renin at the third day after paracentesis greater than 50% over baseline levels up to a value higher than 4 ng/ml per h). CONCLUSIONS: Patients with cirrhosis treated by paracentesis should receive diuretics immediately after this procedure to prevent early recurrence of ascites. The administration of 225 mg/day of spironolactone is a good empiric treatment for non-azotemic patients with cirrhosis, because it is effective in most cases and does not increase the incidence of postparacentesis circulatory dysfunction. The determination of plasma levels of renin or aldosterone prior to paracentesis predicts the efficacy of spironolactone in the prevention of ascites recurrence.

Aldosterone↗

Lymphoproliferative responses to hepatitis C virus core, E1, E2, and NS3 in patients with chronic hepatitis C infection treated with interferon alfa.

The quality of the hepatitis C virus (HCV)-specific T-cell response may greatly determine the course of an HCV infection. An adequate T-cell response may contribute to a successful clearance of the virus and a rapid recovery from the disease. An inadequate response may lead to viral persistence and may eventually contribute to the pathogenesis of hepatocellular damage in chronic disease. The effect of interferon alfa (IFN-alpha), presently the most popular therapeutic agent for chronic HCV infections, on HCV-specific T-cell responses is completely unknown. To demonstrate the presence of HCV-specific T lymphocytes during chronic HCV infections, to know their antigenic specificities, and to examine possible effects of IFN-alpha treatment on their presence and antigen recognition patterns, we have stimulated peripheral blood mononuclear cells (PBMC) from 35 chronic HCV patients with nine pools of synthetic peptides representing the HCV Core, E1, and E2 proteins as well as with a recombinant NS3 protein. The proliferative responses of PBMC from 16 healthy control subjects toward these antigens were measured for comparison. Lymphoproliferative responses of patients with chronic HCV infections were assayed either before (in 10 patients), during (in 13 patients), or after (in 21 patients) treatment with IFN-alpha. The analysis showed that PBMC from most HCV patients consistently recognized the COOH-terminal part of the core protein. E1, E2, and NS3 were recognized less frequently. This recognition pattern was not related to the therapy with IFN-alpha nor to the clinical response of the patient toward this therapy. The response to the Core protein could be fine-mapped to the COOH-terminal region encompassing amino acids (aa) 73 to 92, 121 to 140, 145 to 164, and 157 to 176.

Adult↗

Distribution and concentrations of 5-aminosalicylic acid in rectosigmoid biopsy specimens after rectal administration.

PURPOSE: Using the autofluorescent properties of 5-aminosalicylic acid (5-ASA), we studied the penetration and distribution of this molecule in human colonic biopsies at different time intervals after administration of 5-ASA enemas. METHODS: Fluorescence scores of rectosigmoidal biopsy specimens were compared with 5-ASA and acetyl-5-aminosalicylic (Ac-5-ASA) concentrations, determined by high-performance liquid chromatography, in adjacent biopsies and in serum samples. RESULTS: 5-ASA penetrates into the rectal mucosa and into the epithelial cells after local application by means of an enema. We found a characteristic 5-ASA staining of two intramucosal structures that need further identification: intraepithelial triangular configurations and "5-ASA scavengers" in the lamina propria. Fluorescence scores correlate well with 5-ASA concentrations in adjacent biopsies (r = 0.67; P < 0.005) and correlate even better with serum concentrations of 5-ASA (r = 0.84; P < 0.005) and Ac-5-ASA (r = 0.80; P < 0.005), hence reflecting the amount of systemically absorbed and metabolized 5-ASA. CONCLUSION: 5-ASA penetrates into the rectal mucosa after local application. Local availability, assessed by means of fluorescence microscopy, correlates well with serum concentrations.

Administration, Rectal↗

Polyarteritis nodosa and the antiphospholipid syndrome.

We report a case of biopsy-proven polyarteritis nodosa (classic type in association with the antiphospholipid syndrome. Medium-sized arteriopathy was confirmed on visceral angiography. Elevated anticardiolipin antibodies were detected before initiating therapy with methylprednisolone and IV pulse cyclophosphamide. Rapid subsidence of symptoms correlated with a gradual normalisation of the erythrocyte sedimentation rate. After 6 months of therapy anticardiolipin antibodies were within normal limits. Only one similar case has been reported so far.

Angiography↗

Lusoria dysphagia in a patient with retroperitoneal fibrosis and Riedel's thyroiditis.

The case history of a 68-year-old woman with progressive dysphagia caused by extrinsic compression of the oesophagus by an aberrant right subclavian artery or arteria lusoria is presented. Previous history mentioned a Riedel's thyroiditis, idiopathic retroperitoneal fibrosis and an aortic sclerosis. The authors want to report the case because it is an example of an association between lusoria dysphagia and retroperitoneal fibrosis, the connective tissue disease responsible for Riedel's thyroiditis, and perhaps, aortic sclerosis. This is the first report of this particular association.

Aged↗

Long-term evolution of gut inflammation in patients with spondyloarthropathy.

BACKGROUND & AIMS: Intestinal inflammation has been observed in patients with spondyloarthropathy (SpA). This prospective study reports the evolution of the intestinal inflammation observed in patients with SpA. METHODS: One hundred twenty-three patients with SpA who had undergone initial endoscopy were clinically reassessed. Intestinal evolution was evaluated by ileocolonoscopy and the histological study of biopsy specimens in 49 patients. RESULTS: Articular remission rates were independent of initial gut inflammation and associated with endoscopic and histological remission. Persistent gut inflammation was observed in active joint disease. Gut inflammation rarely disappeared, despite the persistence of articular complaints. Initial chronic gut inflammation implied a high risk of evolution to ankylosing spondylitis. Evolution to inflammatory bowel disease (IBD) was observed in 7% of patients. Mainly patients with initial chronic inflammation and mild complaints of diarrhea were at risk. Sulfasalazine was more frequently needed in the treatment of patients with gut inflammation with a beneficial effect on articular and intestinal evolution but did not prevent evolution to IBD. CONCLUSIONS: This study supports the etiopathogenetic role of the gut in SpA. Presence of chronic gut inflammation and mild complaints of diarrhea implies a high risk of evolution to ankylosing spondylitis and IBD. Sulfasalazine has a beneficial effect on articular activity by controlling gut inflammation, but it cannot prevent evolution to overt IBD.

Adolescent↗