Search

Adults with dyschezia are occasionally diagnosed as having megarectum when anorectal manometry identifies rectal sensory disturbances. It remains difficult however to ascertain whether this state represents a part of the pathophysiological process responsible for symptoms, or just an associated phenomenon. The aim of this study was to highlight the symptomatic and functional features encountered in patients with dyschezia and megarectum, and to compare them with those obtained in an asymptomatic group and in a group of patients complaining of dyschezia without manometric megarectum.The maximum tolerable volume (MTV) was defined as the highest tolerable volume which induced painful and irrepressible repletion upon inflation of the rectum with air. The upper normal range of MTV (330 mL) was obtained from rectal manometry performed in a group of 18 healthy volunteers and asymptomatic patients (mean age: 37.8 +/- 14 years, 12 F, 6 M). Between February 90 and February 92, 27 consecutive adults (48 ans +/- 15 years, 26 F, 1 M) suffering from dyschezia were found to have abnormally increased MTV, and were compared to a group of 35 patients (47 +/- 15.3 years, 34 F, 1 M) with dyschezia with MTV within normal ranges. Symptomatic patients underwent detailed interrogation, clinical examination, anorectal manometry, and evacuation proctography.Parity, prevalence of hysterectomy, symptoms and natural history did not differ between the two groups except for increased use of antidepressive agents in the megarectum group.(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of this study was to evaluate the prognosis and the determinants of survival in cirrhotics presenting with variceal bleeding. One hundred and ninety one consecutive patients with cirrhosis (alcoholic 93 percent) were enrolled between 1983 and 1988. Treatment was principally but not exclusively based on early endoscopic sclerotherapy. At admission all patients were classified according to Child-Pugh's classification (class A = 16 percent; class B = 53 percent; class C = 31 percent). The rebleeding rates at 48 hours and for the entire hospitalisation were 11 and 30 percent respectively. Actuarial survival rates were 45, 40, and 37 percent at 12, 18, and 36 months, respectively. Prognostic factors, as determined by uni- and multivariate analysis (Cox model), corresponded to Child-Pugh's score, to the five components, and the occurrence of early bleeding recurrence. This study also showed that: i) the role of Child-Pugh's classification on long-term prognosis is determined during the 3 months following index bleeding; ii) early rebleeding is a significant prognostic factor, particularly in Child-Pugh's class B patients; iii) there are few indicators of early rebleeding (serum albumin level, presence of gastric varices at initial endoscopy). Prognosis of variceal bleeding is still severe in cirrhosis but efforts made to prevent early bleeding recurrence seem to be fully justified.

Chemokines and their receptors are involved in the migration of different mononuclear cells. Among them macrophages-derived chemokines (MDC) and thymus-and activation regulated chemokine (TARC) belong to a new cluster of genes involve in Th2 lymphocytes homing. Cytokines appear to play a significant role in pathogenesis of inflammatory bowel diseases with an excessive Th1 response in chronic lesions of Crohn's disease (CD) and a Th2 pattern in both earlier mucosal CD lesions and in mucosa of ulcerative colitis (UC). Here we demonstrate that RNAm coding for MDC and TARC are expressed in mucosa from CD and UC patients. Using real-time fluorescent RT-PCR, MDC and TARC mRNA were increased in CD inflamed mucosa. Moreover MDC and TARC transcripts were increased in inflamed CD specimen compared to non-involved CD mucosa. These differences both discriminate CD from UC patients. Additionally, MDC protein was produced in isolated mononuclear cells from peripheral blood (PBMC) or mucosa (LPMC) from UC and CD patients: spontaneously, MDC production from PBMC was increased in CD compared to UC patients. MDC production from CD PBMC was also higher than that found in healthy controls. Together, these data indicate that MDC should be involved in the lymphocytes homing in mucosa from CD patients.

Gastroduodenal duplication is a rare congenital entity. Preoperative diagnosis is difficult because symptoms are usually non specific and can mimick pancreatitis. We report 2 cases of gastric and duodenal cystic duplication in adults presenting as pancreatitis. Chronic pancreatitis was observed on endoscopic retrograde pancreatography and confirmed at laparotomy in both cases. Pancreatitis was probably related to alcoholism in one case, but might have been secondary to duplication in the other. In both cases, duplication was misinterpreted initially as a pseudocystic complication of pancreatitis until laparotomy was performed. These 2 cases lead us to discuss the relationship between duplication and pancreatitis.

Endoscopic information was obtained for 52 patients with ulcerative proctitis (23 F, 29 H) seen during a ten-year period. The median follow-up was 68 +/- 8 months. During the first referral period (38 patients experienced a first attack), endoscopic particularities were available: inflammation involved the anal mucosa above the dental line (n = 16), the whole circumference of rectal mucosa (n = 19) or the anterior wall exclusively (n = 33). The upper limit was 12.2 +/- 0.6 cm from the anal verge. Inflammatory lesions were higher in circumferencial conditions, when patients were older (late onset disease) but sex and ethnic state did not influence results of endoscopic presentation. Exulcerations or superficial ulcers were visualized in 16 and spontaneous bleeding in 43. Forty-five patients achieved clinical accuracy after 9.4 +/- 1 ms, but 32 only a complete endoscopic remission. Mean number of relapses was 3.6 +/- 0.4; 13 patients experienced a single attack. During relapses, inflammation was stable in 11 of 38 patients. Extension to the rectum in rectosigmoid junction, and sigmoid and above by 6, 14, and 7 patients respectively. After 5 years follow-up, the cumulative risk of further extension was 37 percent and 13 percent, respectively. Low abdominal pain, an family history of ulcerative colitis, and high inflammatory lesions at referral were significantly associated with a higher risk of extension. Cancer did not occur and not surgery was necessary during the follow-up. Idiopathic proctitis is perhaps at the "benign end" of the spectrum of ulcerative colitis. Nevertheless, its endoscopic particularities should be noticed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ulcerative colitis (UC) is a chronic disabling and relapsing inflammatory disease of the colonic mucosa that for more than half of patients results in chronic intermittent or continuous symptoms of increased stool frequency, fecal urgency and rectal bleeding The aim of the present work was to assess experimental ways and new therapeutic strategies with current treatments to improve long-term outcomes of UC. We focused experimental work on the peroxisome proliferator-activated receptor γ (PPARγ), a key factor of gut homeostasis and a target of mesalamine. The mechanism of primary impaired expression of PPARγ in colonic epithelial cells (CEC) during UC remains unknown. We demonstrated the control of PPARγ expression by intracellular CEC production of cortisol and the lack of cortisol production during UC that may participate towards the decreased expression of PPARγ. Furthermore hypoxia, a driver of mucosal inflammation during UC, markedly decreased PPARγ expression through the over-expression of miR-27a that was reversible by the use of sildenafil. From a clinic point of view, we assessed the efficacy and feasibility of a treat to target strategy which implies treatment optimization to achieve mucosal healing a key factor of long-term outcomes. Finally we addressed the long-term outcomes of patients treated with infliximab including the case of refractory proctitis., La rectocolite hémorragique (RCH) est une maladie inflammatoire chronique de l'intestin responsable d'un handicap et d'une altération de la qualité de vie pouvant exposer les patients à des complications sévères en dépit des thérapeutiques actuelles. L'objectif de cette thèse était d'analyser les voies possibles d'amélioration de la prise en charge thérapeutique des patients à partir de données expérimentales et cliniques. Au niveau expérimentale nous nous sommes intéressés au mécanisme impliqué dans la régulation de l'expression de PPARγ, récepteur nucléaires aux propriétés anti-inflammatoires, primitivement diminuée au cours de la RCH et cible des 5-aminosalicylés. Il a été montré que son expression était d'une part sous le contrôle de la stéroidogenèse intraépithéliale, elle-même sous contrôlée par LRH-1 et d'autre part que l'hypoxie épithéliale diminuait son expression via une sur-expression de miR-27a. Par ailleurs, les effets de l'hypoxie sur l'expression de PPARγ étaient inversés en présence de sildénafil. Sur le versant clinique, l'analyse d'une nouvelle stratégie thérapeutique ciblant la cicatrisation muqueuse, c'est à dire l'abrogation de l'inflammation colique macroscopique était efficace et possible dans la pratique clinique. Cet objectif semble aujourd’hui fondamental pour diminué la morbi-mortalité induite par cette maladie. Enfin nous avons observé l'efficacité des anti-TNF dans le cas spécifique de la rectite réfractaire et l'importance de son utilisation prolongée pour éviter les rechutes de la maladie et l’obtention d’une rémission prolongée.

Ulcerative colitis (UC) is a chronic disabling and relapsing inflammatory disease of the colonic mucosa that for more than half of patients results in chronic intermittent or continuous symptoms of increased stool frequency, fecal urgency and rectal bleeding The aim of the present work was to assess experimental ways and new therapeutic strategies with current treatments to improve long-term outcomes of UC. We focused experimental work on the peroxisome proliferator-activated receptor γ (PPARγ), a key factor of gut homeostasis and a target of mesalamine. The mechanism of primary impaired expression of PPARγ in colonic epithelial cells (CEC) during UC remains unknown. We demonstrated the control of PPARγ expression by intracellular CEC production of cortisol and the lack of cortisol production during UC that may participate towards the decreased expression of PPARγ. Furthermore hypoxia, a driver of mucosal inflammation during UC, markedly decreased PPARγ expression through the over-expression of miR-27a that was reversible by the use of sildenafil. From a clinic point of view, we assessed the efficacy and feasibility of a treat to target strategy which implies treatment optimization to achieve mucosal healing a key factor of long-term outcomes. Finally we addressed the long-term outcomes of patients treated with infliximab including the case of refractory proctitis., La rectocolite hémorragique (RCH) est une maladie inflammatoire chronique de l'intestin responsable d'un handicap et d'une altération de la qualité de vie pouvant exposer les patients à des complications sévères en dépit des thérapeutiques actuelles. L'objectif de cette thèse était d'analyser les voies possibles d'amélioration de la prise en charge thérapeutique des patients à partir de données expérimentales et cliniques. Au niveau expérimentale nous nous sommes intéressés au mécanisme impliqué dans la régulation de l'expression de PPARγ, récepteur nucléaires aux propriétés anti-inflammatoires, primitivement diminuée au cours de la RCH et cible des 5-aminosalicylés. Il a été montré que son expression était d'une part sous le contrôle de la stéroidogenèse intraépithéliale, elle-même sous contrôlée par LRH-1 et d'autre part que l'hypoxie épithéliale diminuait son expression via une sur-expression de miR-27a. Par ailleurs, les effets de l'hypoxie sur l'expression de PPARγ étaient inversés en présence de sildénafil. Sur le versant clinique, l'analyse d'une nouvelle stratégie thérapeutique ciblant la cicatrisation muqueuse, c'est à dire l'abrogation de l'inflammation colique macroscopique était efficace et possible dans la pratique clinique. Cet objectif semble aujourd’hui fondamental pour diminué la morbi-mortalité induite par cette maladie. Enfin nous avons observé l'efficacité des anti-TNF dans le cas spécifique de la rectite réfractaire et l'importance de son utilisation prolongée pour éviter les rechutes de la maladie et l’obtention d’une rémission prolongée.