George T. Fantry

Increased expression and cellular localization of inducible nitric oxide synthase and cyclooxygenase 2 in Helicobacter pylori gastritis

BACKGROUND & AIMS Inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 are important regulators of mucosal inflammation and epithelial cell growth. To determine the role of iNOS and COX-2 in Helicobacter pylori-induced tissue injury, we compared their gene expression in H. pylori-induced gastritis with that in normal gastric mucosa and in non-H. pylori gastritis. METHODS In 43 patients, we assessed H. pylori infection status, histopathology, messenger RNA (mRNA) and protein expression, and cellular localization of iNOS and COX-2. RESULTS By reverse-transcription polymerase chain reaction (RT-PCR), antral iNOS and COX-2 mRNA expression was absent to low in normal mucosa (n = 10), significantly increased in H. pylori-negative gastritis (n = 13), and even more markedly increased in H. pylori-positive gastritis (n = 20). Increased iNOS and COX-2 levels were confirmed by Northern and Western blot analysis and were both greater in the gastric antrum than in the gastric body of infected patients. Immunohistochemistry also showed increased expression of both genes in H. pylori gastritis: iNOS protein was detected in epithelium, endothelium, and lamina propria inflammatory cells, and COX-2 protein localized to mononuclear and fibroblast cells in the lamina propria. CONCLUSIONS iNOS and COX-2 are induced in H. pylori-positive gastritis and thus may modulate the inflammation and alterations in epithelial cell growth that occur in this disease. Higher levels of iNOS and COX-2 in H. pylori-positive vs. -negative gastritis and in gastric antrum, where bacterial density is greatest, suggest that expression of these genes is a direct response to H. pylori infection.

Decreased Prevalence of Helicobacter pylori Infection in Gastroesophageal Reflux Disease

Background. An increased incidence of reflux esophagitis has been reported after eradication of H. pylori in patients with duodenal ulcer. To determine if H. pylori is associated with lower rates of esophagitis, we studied the prevalence of H. pylori infection in patients with and without reflux esophagitis and a subgroup of patients with concomitant peptic ulcer disease.

Role of EspB in Experimental Human Enteropathogenic Escherichia coli Infection

ABSTRACT Enteropathogenic Escherichia coli (EPEC), a leading cause of diarrhea among infants in developing countries, induces dramatic alterations in host cell architecture that depend on a type III secretion system. EspB, one of the proteins secreted and translocated to the host cytoplasm via this system, is required for numerous alterations in host cell structure and function. To determine the role of EspB in virulence, we conducted a randomized, double-blind trial comparing the ability of wild-type EPEC and an isogenic ΔespB mutant strain to cause diarrhea in adult volunteers. Diarrhea developed in 9 of 10 volunteers who ingested the wild-type strain but in only 1 of 10 volunteers who ingested the ΔespB mutant strain. Marked destruction of the microvillous brush border adjacent to adherent organisms was observed in a jejunal biopsy from a volunteer who ingested the wild-type strain but not from two volunteers who ingested the ΔespB mutant strain. Humoral and cell-mediated immune responses to EPEC antigens were stronger among recipients of the wild-type strain. In addition, four of the volunteers who ingested the wild-type strain had lymphoproliferative responses to EspB. These results demonstrate that EspB is a critical virulence determinant of EPEC infections and suggest that EspB contributes to an immune response.

Gastrocolic and duodenocolic fistulas in Crohn's disease

Crohns disease is a rare cause of gastrocolic and duodenocolic fistulas. Only 83 examples (27 gastric, 52 duodenal, four both) have been described. Weight loss, abdominal pain, and diarrhea are common features but fail to distinguish a fistula from active inflammatory bowel disease. Fecal vomiting is pathognomic but is present in one third of gastrocolic and only 2% of duodenocolic fistulas. Diagnosis is most readily made by contrast radiography, with barium enema being more sensitive than barium meal. Although several gastrocolic fistulas have been successfully treated with long-term 6-mercaptopurine, surgery is the mainstay of therapy. An isolated duodenocolic fistula should not be regarded as the primary indication for operation because most are asymptomatic. Ileocolonic resection with simple gastric or duodenal repair is safe and effective in most cases. An ileocolonic anastomosis should be positioned away from the stomach or duodenum or protected with omentum to prevent recurrent fistulization. A number of fistulas appear to have arisen from gastric or duodenal Crohns, but the vast majority originate from diseased colon.

Immune Evasion by Helicobacter pylori: Gastric Spiral Bacteria Lack Surface Immunoglobulin Deposition and Reactivity with Homologous Antibodies

Background. Helicobacter pylori infection persists in the presence of potent serum and gastric mucosal anti‐body responses against bacterial antigens. The aim of this article is to report on a study determine whether there is antibody deposition on H. pylori in vivo in the stomach of infected patients and whether gastric and cultured forms of H. pylori differ in their antibody reactivity.

Knowledge-Based Modeling and Simulation of Diseases with Highly Differentiated Clinical Manifestations

This paper presents the cognitive model of gastroesophageal reflux disease (GERD) developed for the Maryland Virtual Patient simulation and mentoring environment. GERD represents a class of diseases that have a large number of clinical manifestations. Our model at once manages that complexity while offering robust automatic function in response to open-ended user actions. This ontologically grounded model is largely based on script-oriented representations of causal chains reflecting the actual physiological processes in virtual patients. A detailed description of the GERD model is presented along with a high-level description of the environment for which it was developed.

Iron deficiency anemia due to a Brunner's gland hamartoma

Brunners gland hamartomas are rare benign duodenal tumors often discovered incidentally during endoscopy or on an upper gastrointestinal series. These tumors arise mainly in the duodenal bulb and can present with gastrointestinal bleeding or symptoms of intestinal obstruction. When symptomatic, surgical or endoscopic removal can be safely performed and the prognosis is very good. We describe a 63-year-old man presenting with iron deficiency anemia due to a large Brunners gland hamartoma and review the endoscopic, radiologic, surgical, and pathologic findings.

Inconsistency as a diagnostic tool in a society of intelligent agents

OBJECTIVE To use the detection of clinically relevant inconsistencies to support the reasoning capabilities of intelligent agents acting as physicians and tutors in the realm of clinical medicine. METHODS We are developing a cognitive architecture, OntoAgent, that supports the creation and deployment of intelligent agents capable of simulating human-like abilities. The agents, which have a simulated mind and, if applicable, a simulated body, are intended to operate as members of multi-agent teams featuring both artificial and human agents. The agent architecture and its underlying knowledge resources and processors are being developed in a sufficiently generic way to support a variety of applications. RESULTS We show how several types of inconsistency can be detected and leveraged by intelligent agents in the setting of clinical medicine. The types of inconsistencies discussed include: test results not supporting the doctors hypothesis; the results of a treatment trial not supporting a clinical diagnosis; and information reported by the patient not being consistent with observations. We show the opportunities afforded by detecting each inconsistency, such as rethinking a hypothesis, reevaluating evidence, and motivating or teaching a patient. CONCLUSIONS Inconsistency is not always the absence of the goal of consistency; rather, it can be a valuable trigger for further exploration in the realm of clinical medicine. The OntoAgent cognitive architecture, along with its extensive suite of knowledge resources an processors, is sufficient to support sophisticated agent functioning such as detecting clinically relevant inconsistencies and using them to benefit patient-centered medical training and practice.

Primary posttransplant lymphoproliferative disorder of the gallbladder in a lung transplant patient presenting with acute cholecystitis.

BACKGROUND Acute cholecystitis in an immunocompromised host is potentially devastating. Posttransplant lymphoproliferative disorder (PTLD) is a well described complication of immunosuppressive therapy used after solid organ transplantation; however, isolated involvement of the gallbladder has not been described. METHODS Case report format is used. RESULTS We report a case of PTLD isolated to the gallbladder, as well as histological evidence of acute cholecystitis, in a patient who presented with signs and symptoms of acute cholecystitis 1 year after single lung transplant. CONCLUSIONS PTLD can occur in the setting of acute cholecystitis and may be missed if careful pathological examination is not undertaken.

Confounding Factors in the Detection of Helicobacter pylori Infection in Patients With Upper Gastrointestinal Bleeding

Confounding Factors in the Detection of Helicobacter pylori Infection in Patients With Upper Gastrointestinal Bleeding