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Biomedical subjects

André Van Gossum

Publications and source records attributed to André Van Gossum.

13 recordsLinked to original sources

Diarrhoea in the critically ill.

PURPOSE OF REVIEW: The purpose of this review is to update the knowledge on diarrhoea, a common problem in critically ill patients. Epidemiological data will be discussed, with special emphasis on diarrhoea in tube-fed patients and during antibiotic therapy. The possible preventive and therapeutic measures will be presented. RECENT FINDINGS: The need for concise definitions of diarrhoea was recently re-emphasized. The use of pump-driven continuous instead of intermittent enteral feeding is less often associated with diarrhoea. The discontinuation of enteral feeding during diarrhoea is not justified. Clostridium difficile-associated diarrhoea is frequent during antibiotic therapy with quinolones and cephalosporins. Formulas enriched with water-soluble fibres are probably effective to prevent diarrhoea, and promising data on the modulation of gut microflora with probiotics and prebiotics were recently released. SUMMARY: Diarrhoea is common in critically ill patients, especially when sepsis and hypoalbuminaemia are present, and during enteral feeding and antibiotic therapy. The management of diarrhoea includes generous hydration, compensation for the loss of electrolytes, antidiarrheal oral medications, the continuation of enteral feeding, and metronidazole or glycopeptides in the case of moderate to severe C. difficile colitis. The place of enteral formulas enriched with water-soluble fibres, probiotics and prebiotics is not yet fully defined.

Anti-Bacterial Agents↗

No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease.

We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage disequilibrium (LD) between the two genes and (ii) to study the association between CRP polymorphisms and the response to infliximab, particularly the decrease in CRP after treatment, in Crohn's disease patients. FCGR3A (V/F) polymorphism and three CRP polymorphisms (-717G/A, 1444C/T, CRP 4A/G) were determined in 206 healthy blood donors and 189 Crohn's disease patients who had received infliximab for either refractory luminal or fistulizing Crohn's disease. Clinical response was defined as complete, partial or absent according to the same definition as in controlled trials. The biological response was defined on the basis of CRP decrease. There was no LD between CRP and FCGR3A in healthy donors or Crohn's disease patients. CRP polymorphisms had no impact on CRP decrease after infliximab. The proportions of Crohn's disease having a positive clinical or biological response were not statistically different among the various genotypes of CRP polymorphisms. There was no LD between CRP and FCGR3A polymorphisms. CRP polymorphisms were not associated with the response to infliximab in Crohn's disease.

Adolescent↗

Lymphotoxin alpha gene in Crohn's disease patients: absence of implication in the response to infliximab in a large cohort study.

A haplotype in the lymphotoxin alpha (LTA) gene has been associated with a lack of response to infliximab in a small cohort of Crohn's disease (CD) patients. The present study aimed to confirm the implication of this haplotype in the response to infliximab in a larger cohort of Caucasian patients. The response to the first infusion with infliximab was evaluated in 214 Caucasian patients with either luminal (n=150) or fistulising (n=64) CD. Clinical response was based on the decrease in CD Activity Index (luminal) or on the evolution in the fistula discharge (fistulising). Biological response was assessed in 139 patients who had elevated C-reactive protein (CRP) before treatment and for whom CRP values were also available after treatment. A positive biological response was defined as a decrease in CRP of at least 25%. The patients were genotyped for six polymorphisms in the LTA gene. A positive clinical response was present in 65.4% of the patients and a positive biological response was observed in 80.6% of the patients. No association was found with any of the studied polymorphisms, nor with the previously published LTA haplotype and the response to infliximab. We could not confirm an association between the LTA locus and clinical or biological response to infliximab in a large cohort of CD patients.

Adult↗

The TNF/ADAM 17 system: implication of an ADAM 17 haplotype in the clinical response to infliximab in Crohn's disease.

Infliximab, a chimeric anti-tumour necrosis factor (TNF)-alpha antibody induces a clinical response in 70% of Crohn's disease patients and the response to infliximab therapy could be partially determined by genetic factors. The implication of both transmembrane and soluble forms of the TNF-alpha in the mechanism of action of infliximab has been demonstrated. The aim of our work was first to perform a complete study of TNF variants role in the response to infliximab in Crohn's disease. Secondly, considering the role of ADAM 17 in TNF-alpha shedding, the ADAM 17 locus was also studied. The response to infliximab was evaluated in 222 Caucasian Crohn's disease patients with a luminal (n=160) or fistulizing (n=62) form of the disease. Clinical and biological response evaluation was based on the Crohn's Disease Activity Index score and C-reactive protein level evolutions, respectively. The entire TNF gene was sequenced on the complete cohort. Twelve single nucleotide polymorphisms spanning the ADAM 17 locus were studied and haplotypes rebuilt. A clinical response was observed in 64% of the patients and biological response in 77.1% of patients. No association was found between the TNF gene and the response to infliximab. One haplotype in the ADAM 17 region was associated with a clinical response to infliximab in CD patients (adjusted P=0.045). In conclusion, our results exclude, with a reasonable power, an implication of the TNF gene in the response to infliximab in Crohn's disease, but reveal a potential role of the ADAM 17 gene in this response.

ADAM Proteins↗

Predictive factors of positive findings in patients explored by push enteroscopy for unexplained GI bleeding.

BACKGROUND: The diagnostic yield of push enteroscopy (PE) in patients with unexplained overt GI bleeding is about 30%. The aim of this study was to assess for predictive factors of positive findings. METHODS: A total of 182 patients referred to two endoscopic centers (European Georges Pompidou Hospital [Paris, France] and Erasmus Hospital [Brussels, Belgium]) for unexplained overt GI bleeding (melena [57%], hematochezia [26%], or hematochezia associated with melena [17%]) were included in this retrospective study. Predictive factors associated with positive findings at upper PE were studied by using uni- and multivariate analysis. RESULTS: The overall diagnostic yield of upper PE was 34% (62/182), but lesions were found beyond the second duodenum in 25% of the patients (45/182). Factors significantly associated with positive findings at upper PE were the following. (1) In univariate analysis: the presence of melena, Hb level <7 g/dL, blood transfusion >4 units per patient, chronic renal failure, disorder of hemostasis or effective anticoagulant treatment, history of intestinal arteriovenous malformation, and age > 65 years. (2) In multivariate analysis: chronic renal failure and presence of melena. If only jejunal lesions were considered, chronic renal failure was the only predictive factor associated with positive findings at upper PE in multivariate analysis. The severity of GI bleeding did not reach statistical significance ( p = 0.06). Delay between GI bleeding and PE, number of previous standard endoscopies and previous episodes of bleeding were not associated with positive findings in upper PE. CONCLUSIONS: In patients with unexplained overt GI bleeding, upper PE has a higher diagnostic yield in patients with chronic renal failure and patients with melena (vs. hematochezia).

Adolescent↗

Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients.

BACKGROUND: Addition of glutamine to enteral nutrition formulas is consistently associated with a significant decrease in septic morbidity in critically ill patients, possibly related to the attenuation of gut dysfunction. This pilot study was undertaken to compare the effects of enteral administration of two glutamine-enriched formulas containing either additional free glutamine or glutamine-rich proteins, with a standard solution on plasma and mucosal concentrations of glutamine in patients admitted in the Department of Intensive Care. METHODS: Following randomization, glutamine concentration was determined in endoscopically sampled duodenal biopsies and plasma, before and after a 7-day period of continuous administration of the designated solution. RESULTS: The mucosal concentration of glutamine increased in the duodenal biopsies sampled from patients randomized to the solution containing the glutamine-rich proteins (from 3.6 +/- 2.2 to 6.7 +/- 5.2 micro-mol/g protein), but not from the others. There were no differences between the 3 groups in the plasma concentrations of glutamine, which remained stable over time. CONCLUSION: The source of supplemental glutamine can influence gut mucosal glutamine concentrations, suggesting differences in its availability or utilization.

Clinical Trial↗

Helicobacter pylori modulation of gastric and duodenal mucosal T cell cytokine secretions in children compared with adults.

BACKGROUND: In contrast to adults, ulcers are un-common in Helicobacter pylori-infected children. Since immunological determinants influence the outcome of H. pylori infection, we have investigated mucosal T cell responses in H. pylori-infected children and compared them with those of adults and negative controls. MATERIAL AND METHODS: Mucosal biopsies were obtained from 43 patients undergoing an upper GI endoscopy for dyspeptic symptoms. The concentrations of released cytokines and the density of CD3+, CD25+ and CD69+cells were evaluated by flow cytometry, and the numbers of cytokine-secreting cells were measured by ELISPOT. RESULTS: The numbers of isolated antral CD3+ lymphocytes were only significantly raised in infected adults compared with noninfected controls (p < 0.05), whereas the proportion of CD3+ cells expressing activation markers (CD25 or CD69) remained low. In the stomach, IFN-gamma concentrations increased in infected children and infected adults compared with controls (p < 0.05), but IFN-gamma concentrations were tenfold lower in children than in adults (p < 0.01). IL-2, IL-4, IL-10 and TNF-alpha concentrations were similar in infected and in uninfected children and adults. In contrast, in the duodenum, IFN-gamma, as well as IL-4 and IL-10 concentrations were only increased in infected children compared with controls (p < 0.05). The concentrations of these cytokines were similar in both groups of adults who, however, like children, displayed a higher number of duodenal IL-4-secreting cells compared to controls (p < 0.05). CONCLUSION: These results suggest that IFN-gamma secretion in the stomach of H. pylori-infected patients is lower in children than in adults. This could protect children from development of severe gastro-duodenal diseases such as ulcer disease. In addition, infected patients are characterised by a dysregulation of the mucosal cytokine secretion at distance from the infection site.

Adolescent↗

Prevalence of bone disease in patients on home parenteral nutrition.

BACKGROUND & AIMS: The epidemiology of bone disease in home parenteral nutrition (HPN) is unknown. The aim of this paper is to evaluate the prevalence and severity of reduced bone mineral density (BMD) in long-term HPN. DESIGN: Cross-sectional, multicentre study including patients who within the last 12 months had their BMD assessed by dual-energy-X-ray absorptiometry after at least 6 months of HPN. Data on bone pain and fractures, the primary gastrointestinal diseases, nutritional and rehabilitation status and HPN regimen were reviewed. Both the T-score (no. of SD below mean BMD of young subjects) and the Z-score (no. of SD from normal BMD values corrected for sex and age) were analysed. RESULTS: A T -score <-1 at any site of assessment was observed in 84% of the 165 patients enrolled (<or= -2.5 in 41%). Bone pain occurred in 35% and bone fracture in 10% of patients. Both T - and Z-scores were significantly lower in symptomatic patients. The frequency of bone disease was higher in post-menopausal women but did not differ among the subgroups of the primary diseases. Stepwise regression analysis showed the lumbar spine Z -score positively associated with the age at starting HPN and the femoral neck Z-score positively associated with the body mass index. CONCLUSIONS: Bone disease was present in most of the patients on HPN, was of severe degree in one-half of them and symptomatic in one-third. The BMD Z-score appeared predictive of the risk of fracture. The prevalence of bone disease did not differ between the various primary diseases. Age at starting HPN and body mass index appeared to be the major factors associated with BMD Z-scores.

Absorptiometry, Photon↗

Dose-effect of interleukin-10 and its immunoregulatory role in Crohn's disease.

BACKGROUND: Interleukin-10 (IL-10) is currently being extensively studied in clinical trials for the treatment of Crohn's disease (CD). Only marginal effects have, however, been reported, and the dose-response curve was bell-shaped contrasting with the reported data from in vitro experiments. AIM: To use another in vitro model to analyze the effect of rhIL-10 and rhIL-4 on the spontaneous mucosal TNF-alpha secretion in patients with CD, and to characterize the phenotype of the cells targeted by rhIL-10. METHODS: Non-inflamed colon biopsies from CD patients were cultured for 16 hours in presence of different concentrations of rhIL-10 or rhIL-4. The numbers of TNF-alpha-secreting cells among isolated lamina propria mononuclear cells (LPMNC) were estimated by Elispot. RESULTS: Both rhIL-10 and rhIL-4 down-regulate TNF-alpha secretion by LPMNC from CD patients, with a more pronounced effect with rhIL-10. These effects were closely linked to the cytokine concentrations used, with a bell-shaped dose-response curve. Residual TNF-alpha secretion, in the presence of optimal rhIL-10 concentration was mainly attributable to CD3+ T cells. In contrast, at higher rhIL-10 concentrations, CD3- cells contributed significantly to the TNF-alpha secretion. CONCLUSIONS: The in vitro model we used, demonstrates that IL-4, but mostly IL-10, efficiently suppresses TNF-alpha secretion in LPMNC from CD patients, with a dose-response curve similar to results obtained in vivo. Resistance at high rhIL-10 concentrations was associated with a change in the phenotype of TNF-alpha-secreting cells.

Biopsy↗

A prospective comparative study of push and wireless-capsule enteroscopy in patients with obscure digestive bleeding.

OBJECTIVES: To prospectively compare the global and specific diagnostic yields of push and wireless videocapsule enteroscopy for small bowel lesions in patients with obscure digestive bleeding after esogastroduodenoscopy and colonoscopy. METHODS: The patients studied had unexplained chronic iron-deficient anemia or digestive blood loss after routine investigations. Small bowel investigation was performed first with the wireless-capsule (M2A, Given Imaging) and then with the push-enteroscope (Olympus SIF100). RESULTS: Twenty-one patients were included in the protocol (14 females and 7 males), whose mean age was 60 years (range: 18 to 81). All patients had iron-deficient anemia with occult bleeding (n = 16) or overt bleeding (n = 5). A digestive lesion was observed in 14 of 21 cases (66%). Lesions were: esophageal varices (n = 2), reflux esophagitis (n = 1), upper gastrointestinal tract ulcerations (n = 9), intestinal angioectasia (n = 4), ileal varices (n = 1), cecal angioectasia (n = 1) and tumor-like angioma in the jejunum (n = 1). These 19 lesions were discovered by both methods in 10 cases (52%), by push-enteroscopy only in 6 (31%) and by wireless-capsule endoscopy only in 3 (17%). The global diagnostic yield was therefore slightly but not significantly higher for push wireless-capsule enteroscopy (61 vs 52%; NS) and the specific diagnostic yield was similar (20%). Interobserver agreement on the wireless-capsule recordings reached 85% for detection of findings. CONCLUSIONS: In patients with obscure digestive bleeding, no significant difference in diagnostic yield was evidenced between push and wireless-capsule endoscopy. The main advantage of the latter method versus the former was the detection of distal lesions in the small bowel. Wireless-capsule enteroscopy is mandatory for patients with active unexplained bleeding and negative push-enteroscopy, or for defining the extension of a disease involving, for instance, the presence of angioectasia.

Adult↗

[Acute intestinal bleeding due to Taenia solium infection].

Parasite infections of the digestive tract are a rare cause of acute haemorrhage in Western countries. We report here on a case of acute intestinal bleeding due to Taenia solium infection diagnosed at surgery. A 79-year-old white female patient was admitted to our institution for instable angina and severe anaemia secondary to acute intestinal bleeding. The patient's medical history was positive for long-standing microcytic anaemia. A recent diagnostic work-up had revealed the presence of chronic erosive antral gastritis and colonic diverticular disease without acute bleeding. On admission to our department the patient underwent antegrade bowel endoscopy which showed a bleeding site 120 cm caudad to the Treitz ligament in the absence of ulcers and/or neoplastic lesions. The patient was eventually referred to surgery for suspected intestinal angiodysplasia. At surgery no gross lesions of the stomach, bowel or colon were observed. We then performed a custom enterotomy 120 cm caudad to the Treitz ligament and discovered a 250-cm-long tapeworm. The parasite was removed with the aid of a second enterotomy 60 cm cephalad to the previous one and the entire bowel was explored with an intraoperative fiberoptic endoscope. Histology of the parasite revealed a T. solium species. The postoperative course was uneventful and the patient was discharged on postoperative day 10 with a prescription of 2 g/day niclosamide. No recurrent digestive bleeding has so far been reported after a follow-up of 8 months. T. solium infection is a common cause of chronic microcytic anaemia in tropical and subtropical areas. In Western countries intestinal parasite infections are rarely taken into account in the diagnostic work-up of patients affected with chronic anaemia and/or acute digestive bleeding. The mechanisms responsible for acute intestinal bleeding in tapeworm infections are poorly understood and could be related to parasite-induced erosions of the bowel wall or be secondary to manipulations occurring during diagnostic manoeuvres.

Acute Disease↗