A. Brian West

Immunocytochemical evidence of Listeria, Escherichia coil, and Streptococcus antigens in Crohn's disease

Abstract Background/Aims Infectious agents have long been suspected of playing a role in the initiation of Crohns disease. The objective of this study was to search for likely microbial agents in diseased tissues using immunocytochemical techniques. Methods Intestines and mesenteric lymph node specimens of 21 patients from two French families with a high frequency of Crohns disease and from Connecticut were studied. The microbial agents searched for included Bacteroides vulgatus, Borrelia burgdorferi, Escherichia coil, Listeria monocytogenes, Streptococcus spp., bovine viral diarrhea virus, influenza A virus, measles virus, parainfluenza virus, and respiratory syncytial virus. Results Seventy-five percent of the patients with Crohns disease (12 of 16) were positively labeled with the antibody to Listeria. Macrophages and giant cells immunolabeled for this antigen were distributed underneath ulcers, along fissures, around abscesses, within the lamina propria, in granulomas, and in the germinal centers of mesenteric lymph nodes. In addition, 57% (12 of 21) of the cases contained the E. coli antigen, and 44% (7 of 16) contained the streptococcal antigen. The immunolabeling for the latter two agents also occurred within macrophages and giant cells, distributed in a pattern similar to that of Listeria antigen. Conclusions The results suggest that Listeria spp., E. coli, and streptococci, but not measles virus, play a role in the pathogenesis of Crohns disease.

Bacterial Translocation to Mesenteric Lymph Nodes Is Increased in Cirrhotic Rats With Ascites

BACKGROUND/AIMS Cirrhotic patients are predisposed to develop spontaneous bacteremias and/or peritonitis, mainly caused by enteric bacteria. The aim of this study was to investigate if bacterial translocation, which is the passage of bacteria from the intestinal lumen to regional lymph nodes and/or the systemic circulation, is increased in a rat model of cirrhosis. METHODS Rats were studied after 12-16 weeks of CCl4 inhalation, when samples of mesenteric lymph nodes, blood, liver, and spleen for standard bacteriologic cultures and a fragment of colon and liver for histology were obtained. Immunostaining of the cecum was performed using a polyclonal anti-Escherichia coli antibody. RESULTS A significantly greater proportion of rats with cirrhosis and ascites (5 of 9; 56%) had positive mesenteric lymph node cultures compared with cirrhotics without ascites (0 of 9) and normal controls (0 of 12) (P < 0.01). In one cirrhotic rat, E. coli was isolated from both mesenteric lymph nodes and ascites. Rats with cirrhosis and ascites had significantly greater cecal submucosal edema and inflammation than rats with no ascites and controls. Immunoreactivity with E. coli was present in the cecal wall in 3 of 5 animals with E. coli translocation to mesenteric lymph nodes. CONCLUSIONS In cirrhotic rats, bacterial translocation is increased after the development of ascites and may be a major factor in the development of spontaneous infections in cirrhosis.

Family history of cancer and risk of esophageal and gastric cancers in the United States

The worldwide rates for histology‐ and subsite‐specific types of esophageal and gastric cancer reveal strikingly divergent patterns. The contribution of environmental and genetic factors has been explored in several high‐incidence areas, but data on genetic influences are scarce for Western countries. Using data from a multicenter, population‐based, case‐control study on 1,143 cases and 695 controls in the United States, we evaluated whether a family history of digestive or other cancers was associated with an increased risk of esophageal adenocarcinoma (n = 293), esophageal squamous cell carcinoma (n = 221), gastric cardia adenocarcinoma (n = 261) or non‐cardia gastric adenocarcinoma (n = 368). After adjusting for other risk factors, individuals reporting a family history of digestive cancers experienced no increased risk of either type of esophageal cancer but they were prone to adenocarcinomas of the gastric cardia [odds ratio (OR) = 1.34, 95% confidence interval (CI) 0.91–1.97] and non‐cardia segments (OR =1.46, 95% CI 1.03–2.08). This familial tendency, particularly for non‐cardia gastric tumors, was largely explained by an association with family history of stomach cancer (OR = 2.52, 95% CI 1.50–4.23). In addition, family history of breast cancer was associated with increased risks of esophageal adenocarcinoma (OR = 1.74, 95% CI 1.07–2.83) and non‐cardia gastric adenocarcinoma (OR = 1.76, 95% CI 1.09–2.82). Also seen were non‐significant familial associations of esophageal squamous‐cell cancer with prostate cancer as well as non‐cardia gastric cancer with leukemia and brain tumors, though these relationships must be interpreted with caution. Our data point to the role of familial susceptibility to gastric cancer, but not to any form of esophageal cancer, in the United States.

Migration of Salmonella typhi through Intestinal Epithelial Monolayers: An In Vitro Study

This study characterizes the transmigration of enteroinvasive Salmonella typhi in vitro, using a human intestinal epithelial cell line as a model of small intestinal epithelium. C2BBe cells, a subclone of CACO‐2 with a highly differentiated enterocytic phenotype, were grown to maturity on Transwell filters. S. typhi Ty2 and the vaccine strain, Ty21a, the S. typhi mutant X7344 and parent strain SB130, and S. typhimurium 5771 in logarithmic phase were introduced to the upper chamber of the filter units. Numbers of bacteria in the lower chamber, TER and permeability of the monolayer to mannitol were measured over time. Monolayers were examined by light, electron and confocal microscopy to determine the pathway of bacterial transmigration, and intracellular bacteria were estimated by gentamicin assay. Epithelial cell injury was quantified by light microscopy. S. typhi transmigrated earlier and in larger numbers than S. typhimurium, inducing marked changes in electrical resistance and permeability. Unlike S. typhimurium, S. typhi selected epithelial cells in small number and caused their death and extrusion from the monolayers leaving holes through which S. typhi transmigrated. Ty2 consistently transmigrated in larger numbers and with more injury to monolayers than Ty21a. S. typhi crosses the monolayers of C2BBe cells by a paracellular route in contrast to the transcellular pathway described for other Salmonellae. This may be related to the unique pathophysiology of S. typhi infection and the restricted host specificity of this pathogen. In these assays the vaccine strain, Ty21a, is slightly less invasive than its parent, though more invasive than S. typhimurium.

Glutaraldehyde colitis following endoscopy: Clinical and pathological features and investigation of an outbreak

Although potentially noxious compounds are used routinely to disinfect endoscopes, reports of their inadvertent introduction to the gastrointestinal tract, usually attributed to the retention of disinfectant within endoscope channels, are rare. This case report describes the clinical features of glutaraldehyde-induced colitis and the pathology of the mucosal injury in four patients, in at least one of whom the disinfectant was not retained in the endoscope itself. Within 3 months, three patients experienced severe acute proctocolitis < 6 hours after a sigmoidoscopy showing no abnormalities, performed in a small endoscopy unit. Investigation of the units protocols suggested that the most likely cause was retention of 2% glutaraldehyde disinfectant in the endoscope channels, and changes were made to prevent this. When a fourth case occurred 5 months later, the source of the glutaraldehyde was found to be the tubing connecting water bottles to the endoscopes, which was disinfected rigorously but flushed inconsistently between cases. Glutaraldehyde-induced colitis seems similar to ischemic colitis in biopsy specimens and cannot be diagnosed by histological analysis alone. Acute colitis occurring within 24 hours of a colonoscopy showing no abnormalities should be considered iatrogenic and should lead to an investigation of procedures in use for cleaning and disinfecting endoscopic equipment.

Clinical and pathological characteristics of hepatotoxicity associated with occupational exposure to dimethylformamide.

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.

Principal Component Analysis of Dietary and Lifestyle Patterns in Relation to Risk of Subtypes of Esophageal and Gastric Cancer

PURPOSE To carry out pattern analyses of dietary and lifestyle factors in relation to risk of esophageal and gastric cancers. METHODS We evaluated risk factors for esophageal adenocarcinoma (EA), esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and other gastric cancers (OGA) using data from a population-based case-control study conducted in Connecticut, New Jersey, and western Washington state. Dietary/lifestyle patterns were created using principal component analysis (PCA). Impact of the resultant scores on cancer risk was estimated through logistic regression. RESULTS PCA identified six patterns: meat/nitrite, fruit/vegetable, smoking/alcohol, legume/meat alternate, GERD/BMI, and fish/vitamin C. Risk of each cancer under study increased with rising meat/nitrite score. Risk of EA increased with increasing GERD/BMI score, and risk of ESCC rose with increasing smoking/alcohol score and decreasing gastroesophageal reflux disease (GERD)/body mass index (BMI) score. Fruit/vegetable scores were inversely associated with EA, ESCC, and GCA. CONCLUSIONS PCA may provide a useful approach for summarizing extensive dietary/lifestyle data into fewer interpretable combinations that discriminate between cancer cases and controls. The analyses suggest that meat/nitrite intake is associated with elevated risk of each cancer under study, whereas fruit/vegetable intake reduces risk of EA, ESCC, and GCA. GERD/obesity were confirmed as risk factors for EA and smoking/alcohol as risk factors for ESCC.

Multiple focal nodular hyperplasia of the liver associated with hemihypertrophy and vascular malformations

A case of multiple focal nodular hyperplasia of the liver occurring in a 22-year-old woman with musculoskeletal hemihypertrophy and anomalous vascular supply to the liver is described. The patient had Klippel-Trénaunay-Weber syndrome and abdominal pain and tender massive hepatomegaly. Visceral angiography showed marked dilatation of the celiac axis and both the main trunk and peripheral branches of the hepatic artery. Large abdominal veins drained from the dome of the liver into the hepatic veins. The vascular anomalies were evident on contrast-enhanced computed tomography and magnetic resonance imaging. Multiple focal nodular hyperplasia was confirmed by laparoscopic liver biopsy. The findings in this patient support the concept that multiple focal nodular hyperplasia characteristically occurs in a syndromic form and is induced by an irregular arterial supply in the liver, with localized hyperfusion that leads to nodular areas of hepatocyte hyperproliferation.

Benign peptic ulcers penetrating pericardium and heart: Clinicopathological features and factors favoring survival

Penetration of the pericardium and heart by benign peptic ulcers is rare. Before 1965 it was almost invariably fatal, but about 20% of recently reported cases have survived. We report 4 representative cases and review 91 additional cases from the literature. The ulcers arose in esophagus, hiatus hernias, abdominal stomach, and near anastomoses, and the predominant predisposing factor was previous surgery to the esophagogastric region. Whereas penetrating esophageal ulcers had a slightly better prognosis than gastric lesions, the principal determinant of clinical presentation, findings, and prognosis was the site of cardiac involvement. The clinicopathological features of pericardial, atrial, and ventricular involvement are distinct. We evaluate the different implications of these features for diagnosis, management, and prognosis and make some tentative recommendations regarding diagnostic procedures and treatment. Early diagnosis and prompt surgical intervention are critical to successful treatment of this entity, which may present with predominantly cardiac or gastrointestinal symptomatology.

Differences in laser-induced autofluorescence between adenomatous and hyperplastic polyps and normal colonic mucosa by confocal microscopy

Laser-induced autofluorescence has been used to discriminate normal from adenomatous colonic mucosa. However, few studies to date have studied the origin of colonic autofluorescence. Using confocal microscopy (excitation wavelength 488 nm), we have shown that autofluorescence at this wavelength is present predominantly in the lamina propria of normal mucosa but in the epithelium in adenomatous and hyperplastic polyps. The intensity ratio of epithelial cell to lamina propria fluorescence was significantly lower (P<0.0001) in normal mucosa (0.52±0.01) compared with either adenomatous (1.6±0.2) or hyperplastic polyps (1.7±0.15). However, the ratios were not significantly different between hyperplastic and adenomatous polyps. Thus, confocal microscopy enables the detection of the sites of autofluorescence within colonic mucosa and the quantitation of differences in fluorescence between different tissue types.