摘要:Aim: The aim of this study was to establish a method of investigating intestinal eosinophil and neutrophil granulocytes by flow cytometry, and to compare the distribution and activity of these cells in different stages of ulcerative colit is (UC). Methods: Biopsy samples were taken from six locations of the entire col on and from the terminal ileum in 10 patients with active total UC, 10 patients with inactive total UC, eight patients with active distal UC, and 11 control sub jects. Cell suspensions from biopsies and from peripheral blood were incubated w ith fluorophore conjugated monoclonal antibodies. The use of scatter plot-gatin g and specific antibodies was established in a flow cytometry assay. Results: Eo sinophils were more numerous and more active in patients with active UC than in controls. Interestingly, during inactive UC, the number of activated eosinophils was even larger. Eosinophil activity was high in the rectum of patients with di stal colitis but was also slightly elevated in the proximal colon. Neutrophils w ere increased in number and activity during active but not inactive UC. In patie nts with distal colitis, activated neutrophils were only found in the sigmoid co lon and rectum. Conclusion: With this method, we confirm that neutrophils partic ipate in the inflammatory process during active UC, and that they express a rest ing phenotype during remission. The finding of activated eosinophils in inflamed intestine strengthens the view of these cells as proinflammatory and tissue dam aging. Nevertheless, our new finding of high eosinophil activation during inacti ve UC suggests that eosinophils play a role in repair of injured epithelium.
摘要:Anti-liver-kidney microsome type 1 (LKM1) autoantibodies directed against the cytochrome P450 2D6 (CYP2D6) are considered specific markers of type 2 autoimmune hepatitis, but are also found in 5% of sera from patients chronically infected by hepatitis C virus (HCV). Molecular mimicry between HCV proteins and CYP2D6 has been proposed to explain the emergence of these autoantibodies. Anti LKM1 autoantibodies from hepatitis C-infected patients were affinity-purified against immobilized CYP2D6 protein and used to screen a phage display library. CYP2D6 conformational epitopes were identified using phage display analysis and the identification of statistically significant pairs (SSPs). Cross-reactivity between CYP2D6 and HCV protein candidates was tested by immunoprecipitation. Nineteen different clones were isolated, and their sequencing resulted in the mapping of a conformational epitope to the region of amino acids 254- 288 of CYP2D6. Candidate HCV proteins for molecular mimicry included: core, E2, NS3 and NS5a. Affinity-purified autoantibodies from HCV+ /LKM1+ patients immunoprecipitated either NS3, NS5a, or both, and these reactivities were specifically inhibited by immobilized CYP2D6. In conclusion, HCV+ /LKM1 + sera recognize a specific conformational epitope on CYP2D6 between amino acids 254 to 288, the region that contains the major linear epitope in type 2 autoimmune hepatitis patients. Cross-reactivity due to molecular mimicry at the B-cell level was shown between the CYP2D6 and the HCV NS3 and NS5a proteins and could explain the presence of anti-LKMl in patients chronically infected with HCV. Further investigation of the role played by this molecular mimicry in HCV-infected patients may lead to more specific strategies for diagnosis and treatment.
摘要:Objective. The nuclear factor(NF)-κB is one of the pivotal regulators of autoimmunity and inflammation, which has been shown to be activated in the inflamed mucosa of patients with celiac disease(CD). Recently, in the NFKB1 gene promoter region, a common insertion/deletion(-94ins/ delATTG) polymorphism located between two putative key promoter regulatory elements was described. The aim of this study was to investigate the contribution of the -94ins/ delATTG NFKB1 gene promoter functional variant to CD genetic predisposition. Material and methods. A case-control cohort comprising 478 patients with CD and 711 healthy controls as well as a panel of 196 celiac families was genotyped for the 94ins/delATTG NFKB1 polymorphism, using a polymerase chain reaction (PCR) method combined with fluorescence technology. Results. We found no statistically significant differences between CD patients and controls when the -94ins/delATTG genotype and allele distributions were compared. Accordingly, the familial analysis did not reach statistically significant deviation in the transmission of -94ins/delATTG alleles to the affected offspring. Conclusions. From these results, it could be suggested that the -94ins/delATTG NFKB1 polymorphism does not play a major role in CD susceptibility.
摘要:Objective. Animal studies show that small intestinal bacterial overgrowth and infusion of bacterial antigens into portal blood cause hepatic histological changes similar to those seen in primary sclerosing cholangitis in man. It has been suggested that a similar mechanism involving bacterial overgrowth with increased small-bowel permeability may play a pathogenic role in patients with primary sclerosing cholangitis. Material and methods. Twenty-two patients with primary sclerosing cholangitis (13 M, 9 F, median age 37 years, range 21-74 years), 19 of whom (83%) had quiescent inflammatory bowel disease, were included in the study along with 18 healthy volunteers (9 F, 9 M, median age 36 years, range 23-80 years). Small-bowel bacterial overgrowth was denned as the presence of colonic flora > 105 colony-forming units (cfu)/ml from duodenal aspirations. Small-bowel intestinal permeability was assessed as the differential urinary excretion of lactulose/L-rhamnose. Results. Bacterial overgrowth was evident in one patient with primary sclerosing cholangitis (4.5%) (Enterobacter) and in none of the controls. Intestinal permeability in patients with primary sclerosing cholangitis (0.034 (0.026-0.041) (median, interquartile range (IQR)) did not differ significantly from that of the controls (0.033 (0.025-0.041). Conclusions. Small intestinal bacterial overgrowth and increased intestinal permeability does not seem to play an important pathogenic role in patients with primary sclerosing cholangitis.
摘要:PURPOSE:The aim of this study was to investigate the effects of lateral internal sphincterotomy on quality of life in patients with chronic anal fissure using the Gastrointestinal Quality of Life Index and the Fecal Incontinence Quality of Life Scale.METHODS:Adult patients with chronic anal fissure underwent lateral internal sphincterotomy with the open technique.Two hundred forty-four patients completed the Gastrointestinal Quality of Life Index questionnaire at admission and at 12 months postoperatively.The Fecal Incontinence Severity Index score was calculated preoperatively and at 2 and 12 months postoperatively.The Fecal Incontinence Quality of Life Scale was administered to any patient who had a Fecal Incontinence Severity Index score greater than 0 at 12 months postoperatively.RESULTS:The mean preoperative Gastrointestinal Quality of Life Index score was 118.34± 6.33,which developed to 140.74 ± 2.38 postoperatively(P< 0.001) .At the two-month follow-up,18 patients(7.38 percent) had a Fecal Incontinence Severity Index score greater than 0.By 12 months,the number of patients with Fecal Incontinence Severity Index score greater than 0 was reduced to seven(2.87 percent) .These seven patients had a Gastrointestinal Quality of Life Index score similar to that of the group with postoperative Fecal Incontinence Severity Index score of 0,and only three patients(1.22 percent) had evident deterioration in the Fecal Incontinence Quality of Life Scale.The 12-month total Gastrointestinal Quality of Life Index score of the three patients who developed anal abscess/fistula after sphincterotomy(139.33 ± 3.21) was similar to the Gastrointestinal Quality of Life Index score of those without complications.However,the Gastrointestinal Quality of Life Index score of the recurrent cases(111.53 ± 3.53) was apparently low.CONCLUSION:The gastrointestinal quality of life improved significantly following lateral internal sphincterotomy,regardless of the surgical complications or postoperative disturbances of continence.Only 1.2 percent of the patients experienced deterioration in Fecal Incontinence Quality of Life Scale.
摘要:Objectives -To evaluate in naive patients with chronic hepatitis C 1 -the efficacy and safety of one month interferon alpha (IFN-α) induction regimen; 2-the potential virological benefit of a secondary adjunction of ribavirin among HCV-RNA negative patients after 20 weeks of IFN therapy,with or without an initial 4-week IFN induction. Material and methods -151 naive HCV-RNA positive patients presenting with biopsy-proven chronic hepatitis C and elevated ALT were randomised in a 2∶1 ratio in two arms: IFN-α3 MU thrice a week (tiw) for 24 weeks (non-induced patients); IFN-α6 MU daily for two weeks, then 3 MU daily for two weeks then 3 MU tiw for 20 weeks (induced patients). At week 24, HCV-RNA negative patients were randomised to receive in addition or not ribavirin 1-1.2 g daily for 24 additional weeks. Induction efficacy was assessed on the early viral response (EVR) defined as undetectable HCV RNA at week 4 then week 20. Ribavirin efficacy was assessed on the proportion of maintained complete response until the end of follow-up, 24 weeks after discontinuation of treatment. Data were analysed on an intent-to-treat basis. Results -Efficacy of IFN-αinduction: 104 patients were randomised to the non-induction group, 47 to the induction group. Gender, age, genotype distribution and HCV viral load at baseline did not differ significantly between the two groups. There was one treatment discontinuation because of adverse events in induced patients versus four in non-induced patients (P > 0.05). The 4 week EVR was significantly greater in induced patients in patients with HCV genotype 1, 4 or 5 (47%vs 12%, P = 0.0002) only. There was no impact of induction in patients with HCV genotype 2 or 3. Efficacy of ribavirin: at week 24, 28 and 26 HCV-RNA negative patients were randomised to addition of ribavirin or not, respectively. Patients randomised to secondary additive ribavirin were more often HCV-RNA negative at the end of follow-up than patients treated with IFN-αalone: 18/28 (64%) vs 10/26 (39%); P = 0.06. Among patients randomised to bitherapy, the relapse rate was significantly lower in patients with genotype 2 or 3 (0/12 vs 6/13, P = 0.01) and not in those with genotype 1, 4 or 5 (5/11 vs 3/6, P = 0.99). Conclusion-A 4 week IFN-αinduction significantly increases the EVR rate in patients with HCV genotype 1, 4 or 5. Late secondary adjunction of ribavirin to IFN-αfor 6 months in HCV-RNA negative patients after 6 months of IFN-αsignificantly decreases the relapse rate in patients with HCV genotype 2 or 3, but not in patients with genotypes 1, 4 or 5.
摘要:The incidence of hepatitis C (HCV) infection and associated risk factors were prospectively assessed in a cohort of 6,734 Egyptians from 2 rural villages who were negative for antibodies to HCV (anti-HCV). Initial and follow-up sera were tested for anti-HCV by enzyme immunoassay (EIA), and possible incident cases were confirmed by using the microparticle enzyme immunoassay (MEIA) and tested for HCV RNA. All follow-up serum samples converting from negative to positive without detectable HCV-RNA were further tested by recombinant immunoblot assay. Over an average of 1.6 years, asymptomatic anti-HCV seroconversion occurred in 33 people (3.1/1,000 person- years [PY]), including 28 (6.8/1,000 PY) in the Nile Delta village (AES), where prevalence was 24% and 5 (0.8/1,000 PY) in the Upper Egypt village (baseline prevalence of 9% ). The strongest predictor of incident HCV was having an anti- HCV-positive family member. Among those that did, incidence was 5- 8/1,000 PY, compared (P < .001) with 1.0/1,000 PY; 27 of 33 incident cases had an anti-HCV-positive family member. Parenteral exposures increased the risk of HCV but were not statistically significant; 67% of seroconverters were younger than 20 years of age, and the highest incidence rate (14.1/1,000 PY) was in children younger than 10 who were living in AES households with an anti-HCV-positive parent. In conclusion, young children would especially benefit from measures reducing exposures or preventing infection with HCV.
摘要:Background and aims: The diagnostic yield of capsule endoscopy (CE) compared with magnetic resonance imaging (MRI) in small bowel Crohn‘s disease is not well established. We prospectively investigated CE, MRI, and double contrast fluoroscopy in patients with suspected small bowel Crohn‘s disease. Methods: Fifty two consecutive patients (39 females, 13 males) were investigated by MRI, fluorosco py and if bowel obstruction could be excluded-by CE. In 25, Crohn‘s disease wa s newly suspected while the diagnosis of Crohn‘s disease (non-small bowel) had been previously established in 27. Results: Small bowel Crohn‘s disease was di agnosed in 41 of 52 patients (79%). CE was not accomplished in 14 patients due to bowel strictures. Of the remaining 27 patients, CE, MRI, and fluoroscopy dete cted small bowel Crohn‘s disease in 25 (93%), 21 (78%), and 7 (of 21; 33%) c ases, respectively. CE was the only diagnostic tool in four patients. CE was sli ghtly more sensitive than MRI (12 v 10 of 13 in suspected Crohn‘s disease and 1 3 v 11 of 14 in established Crohn‘s disease). MRI detected inflammatory conglom erates and enteric fistulae in three and two cases, respectively. Conclusion: CE and MRI are complementary methods for diagnosing small bowel Crohn‘s disease. CE is capable of detecting limited mucosal lesions that may be missed by MRI, bu t awareness of bowel obstruction is mandatory. In contrast, MRI is helpful in id entifying transmural Crohn‘s disease and extraluminal lesions, and may exclude strictures.
摘要:Objective. The two forms of inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are thought to arise because of an interplay of unfavorable genetic and exogenous factors. During a genome-wide linkage study of IBD, we observed a nominal linkage to chromosome 11p12-q13 that was further confirmed upon fine density mapping. This chromosomal region contains a functional IBD candidate gene coding for tumor necrosis factor receptor-associated factor 6(TRAF6), a signal transducer regulating innate and adaptive immunity as well as bone homeostasis. Material and methods. Using denaturing high-performance liquid chromatography (dHPLC) and DNA sequencing, all exons and exon-intron boundaries of the TRAF6 gene in probands of 95 IBD families were initially screened; this material comprised 20 CD, 39 UC and 36 mixed families. Results. No nucleotide changes in the coding sequence of TRAF6 were detected, but a single-base insertion/deletion polymorphism in a polythymine stretch (containing 8 or 7 thymines, respectively) in intron 3 was identified. However, examination of an extended material of 290 unrelated CD patients, 416 UC patients and 320 healthy blood donors failed to show any association with this 7T/8T variation and IBD, nor was this polymorphism related to specific clinical features in IBD. Conclusions. Our study tends to exclude a good positional and functional candidate gene, TRAF6, as an IBD predisposing gene and lends support to the idea that the function of TRAF6 is important enough not to permit structural alterations of this mediator.
摘要:PURPOSE:This study examines whether preoperative anal manometry and pudendal nerve terminal motor latency predict functional outcome after perineal proctectomy for rectal prolapse.METHODS:All adult patients treated by perineal proctectomy for rectal prolapse from 1995 to 2004 were identified(N = 106) .Forty-five patients underwent anal manometry and pudendal nerve terminal motor latency testing before proctectomy and they form the basis for this study.RESULTS:Perineal proctectomy with levatoroplasty(anterior 88.9 percent;posterior 75.6 percent) was performed in all patients,with a mean resection length of 10.4 cm.Four patients(8.9 percent) developed recurrent prolapse during a 44-month mean follow-up.Preoperative resting and maximal squeeze pressures were 34.2 ± 18.3 and 60.4 ± 30.5 mmHg,respectively.Pudendal nerve terminal motor latency testing was prolonged or undetectable in 55.6 percent of patients.Grade 2 or 3 fecal incontinence was reported by 77.8 percent of patients before surgery,and one-third had obstructed defecation.The overall prevalence of incontinence(77.8 vs.35.6 percent,P60 mmHg(n = 19) had improved postoperative fecal continence relative to those with lower pressures(incontinence rate,10 vs.54 percent;P = 0.004) ,despite having similar degrees of preoperative incontinence.Abnormalities of pudendal nerve function and mean resting pressures were not predictive of postoperative incontinence.CONCLUSIONS:Perineal proctectomy provides relief from rectal prolapse,with good intermediate term results.Preoperative anal manometry can predict fecal continence rates after proctectomy,because patients with maximal squeeze pressures >60 mmHg have significantly improved outcomes.
摘要:Objective. In alcoholic liver disease (ALD), progression from initial steatosis, through hepatitis to cirrhosis is well described, resulting in 20,000 deaths in the UK annually. However, pathological mechanisms are not well understood and drug trials have led to conflicting results. It has been established that alcohol consumption increases hepatic free radical production and oxidant stress has been implicated in the disease process. Material and methods. Markers of lipid peroxidation, antioxidant status, hepatic fibrogenesis, inflammation and liver function were measured in blood and urine from 24 patients with established alcoholic cirrhosis and in 49 age-and sex-matched controls. Results. In the ALD group, lipid peroxidation markers 8-isoprostane and malondialdehyde were significantly increased (p < 0.001), as was the ratio of oxidized to reduced glutathione (p = 0.027). The antioxidants selenium, glutathione (whole blood and plasma) and vitamins A, C and E were all significantly decreased (p < 0.001); median plasma glutathione levels were only 19%of control levels. Type III procollagen peptide (PIIINP), a serum marker of hepatic fibrogenesis, and C-reactive protein (CRP) were both increased (p < 0.001). Urinary 8-isoprostane correlated positively with PIIINP, CRP and markers of cholestasis (alkaline phosphatase and bilirubin) and negatively with glutathione (whole blood), vitamins A and E and albumin. Conclusions. Oxidant stress, as reflected in blood and urine by a wide range of pro-and antioxidant markers, is a significant feature of alcoholic cirrhosis, providing a mechanism by which alcohol intake may be linked to hepatic inflammation and fibrosis. Non-invasive markers could prove valuable in monitoring response to treatment during clinical trials.
摘要:Background: Hereditary non-polyposis colorectal cancer (HNPCC) is clinically defined by familial clustering of colorectal cancer and other associated tumours. Methods: By thorough molecular and clinical evaluation of 41 families, two dif ferent groups were characterised: group 1, 25 families with truncating mutations in MLH1 or MSH2 (12 novel mutations); and group 2, 16 Amsterdam positive famili es without mutations in these genes and without microsatellite instability in th eir corresponding tumours. Results: Significant clinical differences between the se two groups were found. Firstly, earlier age of onset for all colorectal cancers (median 41 v 55 years; p < 0.001) and all tumours (median 4 3 v 56 years; p = 0.022) was observed, comparing groups 1 and 2. Secondly, 68%o f the index colorectal cancers were localised proximally of the splenic flexure in group 1 compared with 14%in group 2 (p < 0.010). Thirdly, more synchronous a nd metachronous colorectal (p = 0.017) and extracolorectal tumours (p < 0.001) w ere found in group 1. Fourthly, a higher colorectal adenoma/carcinoma ratio (p = 0.030) and a tendency towards more synchronousor metachronous adenomas in group 2 (p = 0.084) was observed, indicating a slower progression of adenomas to carc inomas. As three mutation negative tumours revealed chromosomal instability afte r comparative genomic hybridisation, these tumours may be caused by one or more highly penetrant disease alleles from the chromosomal instability pathway. Concl usion: These data show that HNPCC includes at least two entities with clinical a nd molecular differences. This will have implications for surveillance programme s and for cancer research.
摘要:Severe hyperbilirubinemia in a pregnant mother suffering from Crigler-Najjar syndrome type II is a threat to the unborn child and may result in brain injury. We report the case of a Gly71 →Arg/Tyr 486 →Asp homozygous mother of East Asian descent, who was treated with phototherapy during embryogenesis and with phenobarbital during the rest of the pregnancy. This resulted in significantly reduced bilirubin levels in the mother, who gave birth to a healthy boy. A neonatal hyperbilirubinemia resolved spontaneously.
摘要:Objective. Hyper-IgD syndrome(HIDS) is a rare autosomal recessive disease characterized by recurrent fever, lymphadenopathy, diarrhoea, abdominal pain, headache, arthralgia and skin rash. Abdominal symptomatology may mimic inflammatory bowel disease. We report on four patients with HIDS who had been previously investigated for Crohn’s disease (CD). The levels of IgD were measured in a series of patients with CD to evaluate the specificity of this assay in the differential diagnosis between the two conditions. Material and methods. Diagnosis of HIDS was based on clinical criteria as well as immunological or genetic data. IgD levels were measured in the four subjects affected by HIDS, in 59 patients with CD and in a group of 160 healthy controls. Result. All patients underwent a variety of gastroenterological investigations because inflammatory bowel disease was suspected. Ultrasonography was pathologic in all the patients, showing enlargement of mesenteric lymph nodes. Abdominal leucocyte scintigraphy displayed diffuse signals of mild to moderate degree. IgD and IgA levels were elevated in three out of four patients. No difference in IgD values was found in CD patients as compared to the control group. Conclusions. Gastrointestinal complaints associated with recurrent fever and mesenteric adenopathy warrant genetic investigation for HIDS, in order to avoid unnecessary invasive investigations and treatment.
摘要:Aim of the study -The aim of this retrospective multicenter study was to collect data from patients with chronic alcoholic pancreatitis and cystic dystrophy of the duodenal wall in order to better understand the outcome after medical, endoscopic and/or surgical treatment. Patients and methods-The data from medical records of 23 patients consecutively seen in ten primary referral centers from January 1990 to July 2004 were studied. Clinical, biological, and endoscopic features as well as imaging findings were recorded. Response to treatment was noted. Results -Twenty-three patients (20 men), aged 45 years (range: 30-66),with chronic alcohol intake, cystic dystrophy of the duodenal wall, and previously known (N = 14) or simultaneously diagnosed (N = 9) chronic pancreatitis were included. Symptoms most frequently encountered were abdominal pain (N = 22) and weight loss (N = 16). An abdominal ultrasound was available for 10 patients, abdominal computed tomography for 22, upper endoscopy for 18, and endoscopic ultrasonography for 22. Endoscopic ultrasonography enabled diagnosis of cystic dystrophy of the duodenal wall in 19/22 patients. Six patients were symptom-free after alcohol withdrawal. Seven patients received octreotide 200 to 400 μg per day, 5 of whom subsequently underwent surgery (71%). Fourteen patients out of 23 were operated on (61%), 11 of whom underwent pancreaticoduodenectomy and remained symptom-free for 47 months follow-up. Mean follow-up was 56 months (range: 2-78) for non surgical patients (39%) and 47 months (range: 12-108)-for surgical patients (61%). Conclusion -Cystic dystrophy of the duodenal wall complicating chronic alcoholic pancreatitis may be the revealing sign of pancreatitis. Endoscopic ultrasongraphy is the most reliable imaging method for diagnosis. Pancreaticoduodenectomy is the most frequently employed definitive treatment.
摘要:Barrett’s oesophagus and oesophageal adenocarcinoma, although increasingly common, have no known genetic cause. In this report we describe a family with a remarkable history of Barrett’s oesophagus and adenocarcinoma. The index case is a 76-year-old man with adenocarcinoma arising within Barrett’s oesophagus. Two of his three brothers, aged 68 and 78 years, also developed adenocarcinoma arising in Barrett’s oesophagus and the remaining 67-year-old brother has severe dysplasia in biopsies from Barrett’s oesophagus. The sons and daughters of the index case requested screening and all had histologically confirmed short-segment Barrett’s oesophagus. This kindred appears to be genetically susceptible to Barrett’s oesophagus and oesophageal adenocarcinoma. Pooling of data from this and other Barrett’s families may allow successful linkage analysis.
摘要:Objectives -The aim of this study was to evaluate the histological characteristics of adenomatous polyps (AP), non adenomatous polyps (NAP), and colorectal cancers (CRC) diagnosed in the greater Paris area. Material and methods -Pathologists filled out an identification and histological questionnaire for each biopsy or surgical specimen received between 20/09/02 and 20/12/02, which had at least one colorectal polyp or CRC, taken from a patient of the greater Paris area. Results -The participation rate of pathologists was 73.3%and 10 396 patients with 16 681 lesions were included. Lesions consisted in 1 223 CRC among 1 107 patients, 9 280 AP and 6 178 NAP. Mean age of patients with CRC was 68 years, with at least one AP without CRC 62 years, and with at least one NAP without CRC or AP 58 years. The mean number of polyps per patient was 1.4, and increased with age. Average size of AP was larger than that of NAP and the size increased with age for AP but not NAP. pTNM staging of CRC was: pT0, 1%pT1, 4%pT2, 13%pT3, 63%pT4, 19%N0, 55%N1, 24%N2, 19%Nx, 2%. Conclusion -This study provides detailed data on colorectal polyps and colorectal cancers in the greater Paris region, which does not have a cancer registry. Repeated surveys could be helpful for evaluating the efficacy of screening programs in the general population.
摘要:Background: Surveillance colonoscopy is widely recommended in patients with longstanding and extensive ulcerative colitis (UC) in order to detect colorectalneoplasia at an early stage. However, it still remains questionable whether surveillance colonoscopy effectively enables early detection of UC associated neoplasia. There is a great need for sensitive markers to identify individuals at increased risk of neoplasia. The oestrogen receptor (OR) gene shows age related methylation in the colorectal epithelium and is methylated frequently in sporadic colorectal neoplasia, suggesting that OR methylation may predispose to colorectal neoplasia. Aim: To clarify whether analysis of methylation of the OR gene in non-neoplastic epithelium can contribute to prediction of increased neoplasia risk in UC patients. Materials and methods: Atotal of 165 non-neoplastic colorectal epithelia from 30 patients with longstanding and extensive UC, including 13 UC patients with neoplasia and 17 patients without, were evaluated. Methylation specific polymerase chain reaction was performed to determine the methylation status of the OR gene. Results: Methylation of the OR gene was detected in 54 of 70 (77.1% ) non-neoplastic colorectal epithelia in UC with neoplasia but in only 23 of 95 (24.2% ) without neoplasia. Methylation of the OR gene was significantly more frequent in non-neoplastic epithelium from UC with neoplasia than in chronic colitic epithelium from UC without neoplasia. Furthermore, in UC with neoplasia, the OR gene was extensively methylated in non-neoplastic epithelia throughout the colorectum compared with those in UC without neoplasia. Conclusion: These results suggest that analysis ofOR gene methylation may have potential as a useful marker for identifying individuals at increased risk of neoplasia among those with longstanding and extensive UC.
摘要:Objectives -Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. Patients and methods -This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. Results -Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and / or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. Conclusion -These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.
摘要:Background and aims: Bacterial infections are common complications in patients with acute pancreatitis, and translocation of bacteria from the intestinal lumen is probably the first step in the pathogenesis of these infections. As blood cultures in afebrile patients are usually negative, more sensitive methods to investigate this hypothesis in patients are needed. Our group has recently developed a method to detect the presence of bacterial DNA in biological fluids, and we aimed to detect bacterial DNA in patients with acute pancreatitis, as molecular evidences of bacterial translocation. Methods: Samples of blood were obtained on three consecutive days within the first six days after admission. Bacterial DNA was detected using a polymerase chain reaction based method, and an automated DNA nucleotide sequencing process allowed identification of bacteria species. Results: Thirty one consecutively admitted patients with acute pancreatitis were studied. Bacterial DNA was detected in six patients (19.3% ), and the sequencing process allowed identification of Citrobacter freundii and Pseudomonas aeruginosa. In two patients the same bacteria detected at admission was detected 24 hours later (above 99.9% homology of nucleotide sequence). Basic clinical and biochemical characteristics were similar among patients with or without the presence of bacterial DNA. Conclusion: Detection of gram negative bacteria derived bacterial DNA in our series supports the contention that bacterial translocation is a systemic process in approximately 20% of patients with acute pancreatitis that does not seem to be related to the severity of the episode or immediate development of
摘要:Introduction -Laparoscopic rectopexy for complete rectal prolapse offers short-term advantages compared with operations performed by laparotomy. The aim of this prospective study was to report technical and functional outcome after laparoscopic rectopexy to the promontory in consecutive patients operated on by a single surgeon. Patients and methods -From May 1996 to July 2004, 54 consecutive patients (47 women), median age 53 years (range: 16-84 years), underwent laparoscopic rectopexy to the promontory for complete rectal prolapse. Preoperative evaluation included physical examination, dynamic videoproctography and, in patients with constipation, colonic transit time (with radiopaque markers). Postoperative evaluation included the same examinations and a simple global quality-of-life questionnaire. Results -Conversion to laparotomy was required for three patients during the learning curve. Median duration of operation was 157 minutes (range: 50 -370). There was no mortality and morbidity was 5.5%(brachial plexus palsy in two patients and urinary tract infection in one). Median hospital stay was 3.5 days (range: 1 -11). There were 4 recurrences (7.4%). Functional outcome at 12 months showed the presence of constipation in 20.3%of patients (persistence in eight and de novo in three) and the presence of outlet obstruction in 25.9%of patients (persistence in six and de novo in eight). Anal continence improved in 72.4%of the 29 patients who complained of this symptom. The global quality-of-life questionnaire showed a satisfactory result in 96%of patients. Conclusion -Laparoscopic rectopexy to the promontory is a safe and efficient procedure to treat complete rectal prolapse; morbidity is low. Functional outcome is at least equivalent to that obtained with open procedures in terms of continence, constipation and outlet obstruction.
摘要:Liver disease in alpha-1-antitrypsin (α 1AT) deficiency is caused by a gain-of-toxic function mechanism engendered by the accumulation of a mutant glycoprotein in the endoplasmic reticulum (ER). The extraordinary degree of variation in phenotypical expression of this liver disease is believed to be determined by genetic modifiers and/or environmental factors that influence the intracellular disposal of the mutant glycoprotein or the signal transduction pathways that are activated. Recent investigations suggest that a specific repertoire of signaling pathways are involved, including the autophagic response, mitochondrial-and ER-caspase activation, and nuclear factor kappa B (NFκ B) activation. Whether activation of these signaling pathways, presumably to protect the cell, inadvertently contributes to liver injury or perhaps protects the cell from one injury and, in so doing, predisposes it to another type of injury, such as hepatocarcinogenesis, is not yet known. Recent studies also suggest that hepatocytes with marked accumulation of α 1ATZ, globule-containing hepatocytes, engender a cancer-prone state by surviving with intrinsic damage and by chronically stimulating in‘ trans’ adjacent relatively undamaged hepatocytes that have a selective proliferative advantage. Further, this paradigm may apply to other genetic and infectious liver diseases that are predisposed to hepatocellular carcinoma.
摘要:Objective -To report cases of gastrointestinal endoscopies performed with endoscopes that were reprocessed without detergent substance during a period of dysfunction of the automated endoscope reprocessor (AER). Method -A dysfunction of the AER for the cycles requiring detergent substance was reported at the Grenoble University Hospital on March 2005. During this period, 72 patients had potentially been exposed to a contaminated endoscope. A recall procedure was organized and serologic tests (HIV, HCV, HBV) were performed 3 and 6 months after the AER incident. Results -Within the 72 patients convened, 56 (77.8%) were seen in consultation and accepted the serologic screening. Finally, serologic screening was done for 59 patients (81.9%) and no seroconversion for HIV, HCV, or HBV was observed. The final attrition rate was 13 patients (18.1%). Conclusion -No viral infection was transmitted during the AER dysfunction. After this AER incident, the monitoring of the endoscopic procedures and the traceability of the cleaning process were both improved to prevent further incidents.
摘要:Introduction -Sacral neuromodulation is a recognized therapeutic option in severe anal incontinence from neurogenic origins, when medical treatment has failed. Methods -We report the results of this procedure applied in 40 consecutive patients operated on by a single surgeon from August 2001 to June 2004. Mean duration of incontinence was 5 years. There were 33 women and 7 men of mean age 59 (range 29-89). All patients had had medical treatment, 26 had had physiotherapy and 9 had been previously operated on for that problem. Neuromodulation consisted in a temporary electrical stimulation test followed by implantation of a stimulator in case of efficacy. Results -Twenty nine patients had a positive test and were implanted. Ten had a negative test and one is waiting for implantation. From the 29 patients, 23 had uneventful postoperative course. Incontinence score varied from 17 before neuromodulation to 6 after in the 24 patients who were improved. Mean resting pressure, mean maximum squeeze pressure and mean duration of squeeze pressure did not change from pre to postoperative period. Conclusion -Sacral neuromodulation is a safe and efficacious procedure in properly selected anal incontinent patients. However, we observed no correlation between clinical and manometric data.
摘要:The administration of albumin improves circulatory function, prevents hepatorenal syndrome, and reduces hospital mortality in patients with cirrhosis and spontaneous bacterial peritonitis. This randomized unblinded pilot study compared the effect of albumin (10 patients) and the synthetic plasma expander hydroxyethyl starch 200/0.5 (10 patients) on the systemic hemodynamics of patients with spontaneous bacterial peritonitis. Baseline measurements were performed within 12 hours after diagnosis of infection. Patients then received 2 doses of the volume expander (1.5 g/kg bodyweight after baselinemeasurements and 1 g/kg body weight on day 3). Measurements were repeated after infection resolution. Treatment with albumin was associated with a significant increase in arterial pressure and a suppression of plasma renin activity, indicating an improvement in circulatory function. This occurred in the setting of a significant expansion of central blood volume (increase in cardiopulmonary pressures and atrial natriuretic factor) and an increase in systolic volume and systemic vascular resistance. In contrast, no significant changes were observed in these parameters in patients treated with hydroxyethyl starch. Von Willebrand-related antigen plasma levels significantly decreased in patients treated with albumin but not in those treated with hydroxyethyl starch. Serum nitrates and nitrites increased in patients treated with hydroxyethyl starch but not in those treated with albumin. These data suggest an effect of albumin on endothelial function. In conclusion, albumin but not hydroxyethyl starch improves systemic hemodynamics in patients with spontaneous bacterial peritonitis. This effect is due not only to volume expansion but also to an action on the peripheral arterial circulation.
摘要:Uncontrolled studies suggest that transjugular intrahepatic portal-systemic shunting (TIPS) may improve quality of life in patients with refractory ascites. We hypothesized that any improvement of quality of life in patients with TIPS would be matched in controls due to the competing effects of improved ascites and worsened hepatic encephalopathy. Thus, an analysis of quality of life was performed using original data from the North American Study for the Treatment of Refractory Ascites, a multicenter trial of 109 patients randomized to TIPS or repeated large volume paracentesis (LVP) for refractory ascites. Short form 36 (SF-36) surveys were completed at baseline and at 6-and 12-month follow-up. Variables analyzed were: randomization group, number of LVP performed, cumulative volume from LVP, shortness of breath, abdominal distention, abdominal pain, diuretic usage, confusion, hospitalizations, and emergency room visits. Outcomes were changes in physical component scale (PCS) and mental component scale (MCS) of SF-36 results. We constructed multivariable, mixed effects models, including randomization group and baseline MCS and PCS. Changes in PCS and MCS from baseline were similar between the two randomization groups. In multivariate analysis, PCS improvement was associated with lack of confusion, improved ascites, and lack of hospitalizations, but not directly with randomization group. Improvement in MCS was associated with randomization to TIPS and lack of confusion. In conclusion, patients with refractory ascites randomized to TIPS or repeated LVP had similar changes in quality of life. Competing effects of hepatic encephalopathy, requirement for repeated LVP, and need for hospitalizations explain similar changes in quality of life between the two groups.
摘要:To determine the value of pH testing in clinical practice in gastroesophageal reflux disease patients who failed anti-reflux treatment. Patients resistant to standard dose proton pump inhibitor or an H2-blocker underwent pH testing. Randomly selected patients from the proton pump inhibitor failure group underwent the modified acid perfusion test as compared to patients with non-erosive reflux disease. In the proton pump inhibitor failure group (n = 70), 63.8%had a normal pH test as compared to 29%in the H2-blocker group (n = 31) (P = 0.007). Sensory intensity rating and acid perfusion sensitivity score were significantly higher in the non-erosive reflux disease control group than the proton pump inhibitor failure group (P < 0.05). Most patients who continued to be symptomatic on proton pump inhibitor once daily demonstrated a normal pH test and overall lack of increased chemoreceptor sensitivity to acid.
摘要:Appropriate indication for upper gastrointestinal endoscopy (UGE) may be facilitated by referring to qualifying criteria such as those devised by the European Panel (EPAGE) and French Experts (ANAES). This prospective study evaluates the applicability and efficacy of these criteria in clinical practice. Patients and methods -A total of 522 patients was included (55%inpatients, 57%male, mean age 55 years). Appropriateness of referral was evaluated using EPAGE and ANAES criteria sets by a single independent expert. Results -EPAGE criteria were applicable in 71%of cases. Indications for UGE were appropriate, inappropriate and uncertain in 62%, 27%and 11%respectively; 74%, 16%and 10%of clinically significant lesions detected by UGE were disclosed in patients having appropriate, inappropriate and uncertain indications respectively. ANAES criteria were applicable in 81%of cases. Indications for UGE were appropriate in 74%, inappropriate in 26%; 76%and 24%of clinically significant lesions detected by UGE were disclosed in patients having appropriate and inappropriate indications respectively. Whatever the criteria set used, all cancers and most of the severe lesions were observed in patients with appropriate indications: those patients were more often in-patients and were significantly older than patients belonging to the inappropriate group. Conclusion -Reference to EPAGE and ANAES qualifying criteria facilitates patient selection for UGE. Final decision must however rely upon practitioner advice. ANAES criteria are significantly more often applicable than EPAGE ones. However EPAGE referential when applicable is more predictive of the UGE findings.
摘要:Helicobacter pylori genetic diversity and geographic distribution affect the severity of gastric histology; while eradication heals gastritis, the improvement of atrophy and intestinal metaplasia (IM) is still controversial. We investigated whether H. pylori infection and genotypes (cagA- vacA) influence the histological changes and whether eradication resolves these changes. Twenty- one patients (11 duodenal ulcer, 2 gastric ulcer, 8 gastritis) received treatment. Biopsies for CLO, PCR, histology, and culture were collected before and at 1 and 12 months after treatment, and serum samples at 0, 1, 2, 6, and 12 months. H. pylori eradication was achieved in 71% of the patients. Histological scores for H. pylori densities were significantly higher in the antrum and incisura angularis. Scores for mononuclear cell and neutrophil infiltration were significantly higher in regions with a high H. pylori density and improved progressively after eradication. Eight patients with atrophy including five with IM showed no significant changes 12 months after eradication. The cagA gene, detected in 13 (62% ), the vacA- s1a gene, in 20 (95% ), and the vacA- m1 gene, in 12 (57% ) of 21 patients were significantly associated with duodenal ulcer. A gradual decline in antibody titer reached an average of 67% 12 months after eradication. H. pylori infection and the associated genotypes (cagA of Western type) affect the severity of the gastric histology (mild forms of atrophy and IM) and the disease outcome. Eradication of H. pyloriresulted in healing of gastritis, but with no significant improvement in atrophy or IM.