[Use of immunosuppressors in chronic inflammatory intestinal diseases].
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Azathioprine↗
Biomedical subjects
M Lémann
Publications and source records attributed to M Lémann.
[Treatment of Crohn's disease with anti-TNF alpha].
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Antibodies, Monoclonal↗
Foetal outcome in women with inflammatory bowel disease treated during pregnancy with oral mesalazine microgranules.
BACKGROUND: Little information is available about the safety of high doses of mesalazine during pregnancy. AIM: To study the fate of pregnancy and foetal outcome in women taking 1-4 g/day of mesalazine microgranules for inflammatory bowel disease. PATIENTS AND METHODS: Case reports were collected from the Pharmacovigilance Department of Ferring SA, France, from a survey conducted in three gastroenterology units, and from a teratology information service. The evolution of pregnancy and foetal outcome were assessed by questionnaire. RESULTS: The study covered a total of 123 pregnancies (126 foetuses). Ninety-six women took mesalazine during the first trimester, 85 during the second and 83 during the third. The mean daily dose was 2.1+/-0.8 g; 86 women received <3 g/day (low-dose group), 37 women received > or =3 g/day (high-dose group). The following abnormalities were observed in the low-dose and high-dose groups, respectively: ectopic pregnancy (1/0), spontaneous abortions (1/1), foetal death (0/1), premature deliveries (3/5, P < 0.05), congenital malformations (3/1) and one case of lethal oxalosis. Abnormalities were not considered to be related to mesalazine. CONCLUSIONS: The use of oral mesalazine microgranules during pregnancy is safe at doses < or =2 g/day, and probably also at a dose of 3 g/day.
Adult↗
Granulocytic sarcoma of the jejunum: a rare cause of small bowel obstruction.
We report the case of a 40-yr-old man presenting with symptoms of small bowel obstruction. Small bowel x-rays revealed a stricture of the mid-jejunum. Push enteroscopy found a polypoid mass at 1 meter of the ligament of Treitz. Histopathological examination of the biopsy and surgical specimens showed a diffuse infiltrate of the mucosa made of medium to large cells, which were stained on immunohistochemistry by the leucocyte marker CD45 and the histiocyte/monocyte marker CD68 but were negative for the B and T cell markers. Cytological examination of the ascitic fluid revealed many myelobasts with cytoplasmic Auer rods and positive myeloperoxidase staining. There was no evidence of blood or bone marrow involvement suggestive of acute leukemia or myeloproliferative disorders. These findings were consistent with the diagnosis of preleukemic granulocytic sarcoma (or chloroma). Chemotherapy led to complete remission, but 21 months later the patient developed an acute myeloid leukemia. He died from aspergillus pneumonitis, 10 months after bone marrow allograft. Preleukemic granulocytic sarcoma of the small bowel is a rare condition and its diagnosis is usually not easy, requiring histochemical or immunohistochemical studies. Most cases have progressed to acute myeloid leukemia.
Adult↗
Tonic and phasic motor activity in the proximal and distal colon of healthy humans.
In healthy humans, meals stimulate phasic and tonic motor activity in the unprepared distal colon. The response of the proximal colon remains unknown. In this study, we assessed the effect of a liquid meal on proximal and distal colonic motor activity. In 12 healthy volunteers, colonic tone and phasic motility were simultaneously recorded by using an electronic barostat and perfused catheters in the fasting state and in response to a 1,000-kcal meal. The meal significantly increased the phasic activity in the distal colon (230 +/- 46% of the basal value; P = 0.02) but not in the proximal colon (138 +/- 25% of the basal value; P = 0.2). The intrabag volume of the barostat was significantly more reduced in the distal than in the proximal colon (74 +/- 11 vs. 50 +/- 9% of the basal values, respectively; P = 0.04). We conclude that the postprandial response of the unprepared proximal colon is an immediate tonic contraction that is less pronounced than in the distal colon.
Adult↗
[6-mercaptopurine levels and study of blood lymphocyte subsets during azathioprine treatment of Crohn's disease].
OBJECTIVES: Our aim was to study the relationships between clinical efficacy of azathioprine, 6-mercaptopurine pharmacokinetics and changes in peripheral blood lymphocyte subpopulations induced by azathioprine treatment in Crohn's disease. METHODS: Twenty-three patients were prospectively followed up for 1 year. Peripheral blood counts, total lymphocytes, CD3+, CD4+, CD8+, CD25+, CD16+CD56+, CD57+ and CD19+ lymphocyte subpopulations were carried out, using flow cytometry, during azathioprine treatment. Pharmacokinetic studies were performed at day 8 and month 3 by measuring 6-mercaptopurine plasma concentration after an oral dose of azathioprine (2 mg/kg). Results were compared in responders (no activity and no steroids) and non-responders. RESULTS: The decrease in peripheral blood leukocytes and neutrophils was significant after 1 month, reaching 49% and 48% of the pre-treatment values at 1 year; the one of lymphocytes was significant after 6 months and reached 41% at 1 year. Percentages of CD3+, CD4+, CD8+, CD57+, CD16+CD56+ and CD19+ lymphocytes remained unchanged whereas percentage of CD25+ lymphocytes increased from 10% to 28% (P < 0.01). There was a high inter and intraindividual variability of 6-mercaptopurine peak plasma concentration and area under the curve. No significant difference was found between responders (n = 14) and non responders (n = 7) for pharmacokinetic parameters and lymphocyte subpopulations; there was no correlation between lymphocyte subpopulation changes and 6-mercaptopurine pharmacokinetics. CONCLUSION: Monitoring of 6-mercaptopurine plasma concentration and blood lymphocyte subpopulations is of little value in Crohn's disease patients treated with azathioprine.
Adult↗
[Favorable outcome of a severe carcinoid cardiopathy after complete resection of the primary ovarian tumor].
Carcinoid heart disease induced by a primary ovarian carcinoid tumor is very uncommon but offers the opportunity to study its specific outcome. Indeed, unlike to other carcinoid syndromes that occur in the setting of liver metastasis, a complete removal of the primary carcinoid ovarian tumor is often possible in such cases. We report a case of severe carcinoid heart disease secondary to a carcinoid ovarian tumor. Its interest is related to the exhaustive assessment of the cardiopathy and its complete regression after removal of the ovarian tumor. This outcome emphasizes the need for a as complete as possible reduction of humoral secretions in carcinoid heart disease by medical or surgical therapies before discussing valve replacement surgery.
Aged↗
Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.
BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT) in patients with achalasia followed up for six months. METHODS: Fifty five symptomatic patients with manometrically proven achalasia were included in a multicentre prospective trial. Before and two weeks and two months after intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP) was assessed. The symptom score was determined again at six months, clinical improvement being defined by < or = 3, relapse by > 3, and failure as a relapse after two injections or loss to follow up. RESULTS: Except for transient chest or epigastric pain (22%), no side effects were observed. There was a significant decrease in LOSP after treatment. Symptom scores were significantly improved at two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0)) compared with pretreatment values (5.1 (1.8), p < 0.001). At six months, 33 patients had clinical improvement (27 after one injection), 17 were considered failures, and five had just relapsed. Although there was a trend for age (older patients being more responsive), age, sex, prior duration of symptoms, initial symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous or non-vigorous achalasia, previous dilatations, and radiological features were not predictive of results. CONCLUSIONS: This multicentre series confirms that intrasphincteric injection of BT is a safe procedure, resulting in clinical improvement in 60% of patients with achalasia at six months. The therapeutic role of BT in achalasia needs further evaluation with regard to other alternatives.
Adult↗
Local regulation of ileal tone in healthy humans.
We previously showed that a meal induced, in the human terminal ileum, a delayed tonic relaxation, which could be related to the ileal delivery of meal residues and/or endogenous secretions released by a meal. In this study, we assessed the effects of some components of the ileal contents on its motor activity. In six healthy subjects, we studied ileal tonic and phasic motility in response to the infusion into the terminal ileum of different isotonic solutions: saline, glycochenodeoxycholic acid (GDCA), triglycerides, and short-chain fatty acids (SCFA). Tonic activity was not modified by saline, whereas it was significantly decreased by GDCA and triglycerides (maximal increase in intrabag volume 139 +/- 7% and 152 +/- 16%, respectively, P < 0.01), and significantly increased by SCFA (maximal decrease in intrabag volume 72 +/- 4%, P < 0.01). No significant change of phasic activity was evidenced with either solution. We conclude that 1) bile acids and triglycerides not absorbed in the more proximal gut could be involved in the ileal relaxation occurring after eating and 2) local stimulation of chemoreceptors is of importance in the regulation of ileal motility.
Adult↗
[Severe colitis in mucoviscidosis].
We report the association of severe indeterminate colitis with cystic fibrosis in a 21 year old woman, with mild pulmonary involvement, and without digestive or pancreatic symptoms or pancreatic enzyme preparation. Ten cases of inflammatory bowel disease associated with a cystic fibrosis have been reported. Most fit with the diagnostic criteria of Crohn's disease. Although this case was compatible with this diagnosis, we have retained the diagnosis of "severe indeterminate colitis" because of the lack of specific histological features of Crohn's disease. The association between inflammatory bowel disease and cystic fibrosis is probably not fortuitous, although the pathophysiological link between the two diseases is unknown.
Adolescent↗
Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine.
BACKGROUND: Crohn's ulcerative gastrointestinal disease is presently managed through a variety of medical interventions, including-according to severity of illness-anti-inflammatory, immunosuppressive, and corticosteroid agents; and with remedial surgery to correct anatomical abnormalities caused by disease processes. The immunosuppressant azathioprine (or its metabolite, 6-mercaptopurine) is considered an efficient maintenance therapy for Crohn's, but there is always concern about bone-marrow suppression, liver damage, and other adverse effects. For how long persons with this disease should be given these drugs has not been determined. METHODS: Patients who were treated with azathioprine or 6-mercaptopurine for more than 6 months, and who were in prolonged clinical remission (> 6 months without steroids) were followed. The time-to-relapse was analysed in those on treatment, in those who stopped treatment for reasons other than a relapse, and in the whole sample, taking into account that they could be treated with the drugs or not, as a function of time. The influence of concomitant variables on time-to-relapse rate was examined using the Cox proportional hazard model. FINDINGS: In the 157 patients who continued to take the therapy, cumulative probabilities of relapse at 1 and 5 years were 11% and 32% respectively. Female gender, younger age, and a time for achieving remission more than 6 months were associated with a higher risk of relapse. In 42 patients who stopped therapy, probabilities of relapse at 1 and 5 years were 38% and 75%, respectively. Male gender, younger age and duration of remission less than 4 years were associated with a higher risk of relapse. After 4 years of remission on these drugs, the risk of relapse appeared to be similar, whether the therapy was maintained or stopped. INTERPRETATION: Taking into account the potential risks of long-term immunosuppressive therapy, the usefulness of maintaining azathioprine or 6-mercaptopurine in patients who have been in remission for more than 4 years is questionable.
Adolescent↗
Fecal incontinence after pelvic radiotherapy: evidences for a lumbosacral plexopathy. Report of a case.
PURPOSE: Clinical manifestations of radiation-induced lumbosacral plexopathy remain a rare event. We report the case of a 62-year-old woman with neurogenic fecal incontinence that occurred after radiotherapy of cervical carcinoma. METHODS: Anorectal, bladder, and lower limb sensory-motor functions, as biologic and morphologic explorations, were performed on repeated occasions. RESULTS: Anorectal manometry, conduction times of pudendal nerves, sacral latencies, and pudendal nerve-evoked corticals disclosed lesions of the lumbosacral plexus that was confirmed by bladder manometry and electromyography of lower limbs. Biologic and morphologic explorations were within normal ranges. CONCLUSION: Because no other cause except radiation was demonstrated in this case, we suggest that plexopathy may be a late-occurring complication of radiotherapy.
Brachytherapy↗
Intravenous cyclosporine in attacks of ulcerative colitis: short-term and long-term responses.
The present study reports the results of intravenous cyclosporine in 32 patients with refractory and/or severe attacks of ulcerative colitis (UC). Twenty of 32 patients responded to intravenous cyclosporine; cyclosporine was clinically effective and improved colonic lesions. However, one colonic perforation and one postoperative death were observed in two patients with severe endoscopic colitis who had failed to reach clinical remission with high-dose corticosteroids and cyclosporine. Moreover, after a median follow-up of 190 days, only one-third of the patients avoided colectomy. No predictive factor of response to cyclosporine was identified. This study confirms that cyclosporine is effective in severe UC but suggests that its use could be associated with serious complications in patients with severe lesions who had failed to settle with corticosteroids and cyclosporine.
Adolescent↗
Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody.
BACKGROUND: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti-CD4 (B-F5) antibody in severe refractory Crohn's disease. METHODS: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B-F5 was given intravenously at a dose of 0.5 mg. day/kg for 7 consecutive days (patients 1-8). For patients 9-12, B-F5 was given at a dose of 0.5 mg. day/kg on the first day (day 0) and of 1 mg.day/kg on days 1-6. Follow-up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients. RESULTS: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed. CONCLUSION: In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.
Adolescent↗
Colonic ischemia reveals thromboangiitis obliterans (Buerger's disease).
Two years before the appearance of distal peripheral manifestations of thromboangiitis obliterans (Buerger's disease), a young man had acute peritonitis attributable to an ischemic perforation of the sigmoid colon. Only the histological examination of excised tissue was able to differentially diagnose this entity unambiguously.
Adult↗
Methotrexate for the treatment of refractory Crohn's disease.
BACKGROUND: Previous studies suggested that methotrexate has beneficial effects in patients with Crohn's disease. We report our experience with this agent in patients with chronic active Crohn's disease who previously failed to improve with conventional treatment, including azathioprine in most cases. METHODS: Between June 1988 and June 1992, 39 patients with refractory Crohn's disease were treated with methotrexate. In patients with active disease, clinical remission was defined by a Harvey-Bradshaw index of less than 4. For patients also taking corticosteroids, the dates of remission and complete steroid withdrawal were recorded. For patients who achieved clinical remission, and those in clinical remission when methotrexate was started, the relapse rate on methotrexate therapy was noted. RESULTS: In the 37 patients with active disease at methotrexate initiation, the probability of remission was 72% at 3 months. The probability of remission and steroid withdrawal was 42% at 12 months. In patients on clinical remission, the probability of relapse on methotrexate was 58% at 12 months. Twenty-two patients experienced side-effects, but these only warranted methotrexate discontinuation in four cases. CONCLUSIONS: Methotrexate appears effective in most patients with refractory Crohn's disease and its short-term toxicity is acceptable, but the long-term benefit seems more limited.
Adolescent↗
Effect of glucose and lipids on intestinal absorption of sorbitol: role of gastric emptying.
The aim of our study was to test the hypothesis that the better absorption of sorbitol when ingested with glucose could be related to a delayed gastric emptying. We tested the effect of the ingestion of glucose and lipids on the gastric emptying and intestinal absorption of sorbitol in six healthy volunteers, using gastric scintigraphy and hydrogen breath test. After an overnight fast, subjects ingested in random order, on 48-h test periods separated by at least one week, the following solutions: (a) 20 g sorbitol alone; (b) 20 g sorbitol and 20 g glucose; (c) 20 g sorbitol and 9 g lipids. Isotopic acquisitions were taken for 3 h following the ingestion of sorbitol labelled with 111Indium. Hydrogen concentration was measured in end-expiratory samples during 5 h, and the areas under the breath hydrogen curve, reflecting the amounts of sorbitol unabsorbed in the small bowel, were compared between periods. Mean area under the curve was 397 +/- 159 when sorbitol was ingested alone, and this was significantly lower when ingested with glucose or lipids (313 +/- 181 and 337 +/- 135, respectively; P < 0.05). The three curves of sorbitol gastric emptying differed significantly from each other, the gastric emptying being the slowest for sorbitol plus lipids, and the fastest for sorbitol taken alone. We found a positive correlation between the half-emptying time and the hydrogen areas under the curve (r = 0.46, P = 0.05). In conclusion, our study demonstrates that adding glucose or lipids to a solution of sorbitol slows the gastric emptying of sorbitol, resulting in a better intestinal absorption of sorbitol.
Adult↗
Localized epidermolysis bullosa acquisita of the esophagus in a patient with Crohn's disease.
Epidermolysis bullosa acquisita is a rare autoimmune subepidermal bullous disease that affects both the skin and mucosae and is frequently associated with Crohn's disease. We report the case of a 27-yr-old man with Crohn's disease who presented with localized epidermolysis bullosa acquisita of the esophagus, without any other mucosal or cutaneous lesions. The patient was successfully treated with sulfasalazine.
Adult↗