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Hepatitis C, a common chronic bloodborne infection, is found in approximately 2 percent of adults in the United States. Chronic infection is associated with serious morbidity and mortality (e.g., cirrhosis, hepatocellular carcinoma). Testing for hepatitis C is recommended for at-risk populations, and confirmatory testing includes quantification of virus by polymerase chain reaction. The U.S. Preventive Services Task Force recommends against routine screening for hepatitis C virus infection in asymptomatic adults who are not at increased risk of infection (general population). It found insufficient evidence to recommend for or against routine screening in adults at high risk of infection. Current therapy for chronic hepatitis C virus includes pegylated interferon and ribavirin. Therapy is based on factors that predict sustained virologic response, and the goal of therapy is to slow or halt progression of fibrosis and prevent the development of cirrhosis. In the future, multidrug regimens in combination with current therapies may be developed. Patients with chronic hepatitis C virus infection should be advised to abstain from alcohol use. Currently, there is no vaccine available to prevent hepatitis C virus infection; however, persons infected with hepatitis C virus should be vaccinated for hepatitis A and B. The American Association for the Study of Liver Diseases recommends ultrasound surveillance for hepatocellular carcinoma in persons with chronic hepatitis C virus infection and cirrhosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness of presenting individualized colorectal cancer (CRC) risk information for increasing CRC screening rates in primary care patients at above-average risk of CRC., Design: Randomized controlled trial., Setting: Georgia Regents University in Augusta-an academic family medicine clinic in the southeastern United States., Participants: Outpatients (50 to 70 years of age) scheduled for routine visits in the family medicine clinic who were determined to be at above-average risk of CRC., Interventions: Individualized CRC risk information calculated from the Your Disease Risk tool compared with a standard CRC screening handout., Main Outcome Measures: Intention to complete CRC screening. Secondary measures included the proportions of subjects completing fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy., Results: A total of 1147 consecutive records were reviewed to determine eligibility. Overall, 210 (37.7%) of 557 eligible participants were randomized to receive either individualized CRC risk information (prepared by a research assistant) or a standard CRC screening handout. The intervention group had a mean (SD) age of 55.7 (4.8) years and the control group had a mean (SD) age of 55.6 (4.6) years. Two-thirds of the participants in each group were female. The intervention group and the control group were matched by race (P = .40). There was no significant difference between groups for intention to complete CRC screening (P = .58). Overall, 26.7% of the intervention participants and 27.7% of the control participants completed 1 or more CRC screening tests (P = .66)., Conclusion: Presentation of individualized CRC risk information by a nonphysician assistant as a decision aid did not result in higher CRC screening rates in primary care patients compared with presentation of general CRC screening information. Future research is needed to determine if physician presentation of CRC risk information would result in increased screening rates compared with research assistant presentation., (Copyright© the College of Family Physicians of Canada.)

Nonalcoholic fatty liver disease is characterized by excessive fat accumulation in the liver (hepatic steatosis). Nonalcoholic steatohepatitis is characterized by steatosis, liver cell injury, and inflammation. The mechanism of nonalcoholic fatty liver disease is unknown but involves the development of insulin resistance, steatosis, inflammatory cytokines, and oxidative stress. Nonalcoholic fatty liver disease is associated with physical inactivity, obesity, and metabolic syndrome. Screening is not recommended in the general population. The diagnosis is usually made after an incidental discovery of unexplained elevation of liver enzyme levels or when steatosis is noted on imaging (e.g., ultrasonography). Patients are often asymptomatic and the physical examination is often unremarkable. No single laboratory test is diagnostic, but tests of liver function, tests for metabolic syndrome, and tests to exclude other causes of abnormal liver enzyme levels are routinely performed. Imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, can assess hepatic fat, measure liver and spleen size, and exclude other diseases. Liver biopsy remains the criterion standard for the diagnosis of nonalcoholic steatohepatitis. Noninvasive tests are available and may reduce the need for liver biopsy. A healthy diet, weight loss, and exercise are first-line therapeutic measures to reduce insulin resistance. There is insufficient evidence to support bariatric surgery, metformin, thiazolidinediones, bile acids, or antioxidant supplements for the treatment of nonalcoholic fatty liver disease. The long-term prognosis is not associated with an increased risk of all-cause mortality, cardiovascular disease, cancer, or liver disease.

Irritable bowel syndrome is defined as abdominal discomfort or pain associated with altered bowel habits for at least three days per month in the previous three months, with the absence of organic disease. In North America, the prevalence of irritable bowel syndrome is 5 to 10 percent with peak prevalence from 20 to 39 years of age. Abdominal pain is the most common symptom and often is described as a cramping sensation. The absence of abdominal pain essentially excludes irritable bowel syndrome. Other common symptoms include diarrhea, constipation, or alternating diarrhea and constipation. The goals of treatment are symptom relief and improved quality of life. Exercise, antibiotics, antispasmodics, peppermint oil, and probiotics appear to improve symptoms. Over-the-counter laxatives and antidiarrheals may improve stool frequency but not pain. Treatment with antidepressants and psychological therapies are also effective for improving symptoms compared with usual care. Lubiprostone is effective for the treatment of constipation-predominant irritable bowel syndrome, and alosetron (restrictions for use apply in the United States) and tegaserod (available only for emergency use in the United States) are approved for patients with severe symptoms in whom conventional therapy has been ineffective., (Copyright © 2012 American Academy of Family Physicians.)

Introduction: This study examined barriers to colorectal cancer (CRC) screening in people living in rural areas., Methods: We identified 2 rural counties with high rates of CRC and randomly contacted county residents by telephone using a published listing., Results: Six hundred thirty-five of the 1839 eligible respondents (34.5%) between the ages of 50 and 79 years living in McDuffie and Screven counties, Georgia, agreed to complete the survey. The mean age was 62.2 years (SD, ±7.5 years); 72.4% were women, 79.4% were white, and 19.5% were African American. African-American respondents had lower CRC screening rates (50.4%) than whites (63.4%; P = .009). Significantly more African Americans compared with whites reported barriers to CRC screening. Based on logistic regression analyses, having a physician recommend CRC screening had the strongest association with having a current CRC screening, regardless of race., Conclusions: Important racial differences existed between African Americans and whites regarding the barriers to CRC screening and factors impacting current screening. However, endorsement of a small set of questionnaire items--not race--had the strongest association with being current with screening. Physician recommendation for CRC screening had the strongest association with being current with CRC screening.

Upper gastrointestinal bleeding causes significant morbidity and mortality in the United States, and has been associated with increasing nonsteroidal anti-inflammatory drug use and the high prevalence of Helicobacter pylori infection in patients with peptic ulcer bleeding. Rapid assessment and resuscitation should precede the diagnostic evaluation in unstable patients with severe bleeding. Risk stratification is based on clinical assessment and endoscopic findings. Early upper endoscopy (within 24 hours of presentation) is recommended in most patients because it confirms the diagnosis and allows for targeted endoscopic treatment, including epinephrine injection, thermocoagulation, application of clips, and banding. Endoscopic therapy results in reduced morbidity, hospital stays, risk of recurrent bleeding, and need for surgery. Although administration of proton pump inhibitors does not decrease mortality, risk of rebleeding, or need for surgery, it reduces stigmata of recent hemorrhage and the need for endoscopic therapy. Despite successful endoscopic therapy, rebleeding can occur in 10 to 20 percent of patients; a second attempt at endoscopic therapy is recommended in these patients. Arteriography with embolization or surgery may be needed if there is persistent and severe bleeding.

Purpose of Review: Acute-on-chronic liver failure (ACLF), a syndrome precipitated by acute liver injury in patients with advanced cirrhosis, is associated with multiorgan dysfunction and high rates of mortality. Liver support systems have been developed in an attempt to improve survival of patients with ACLF by providing a bridge until recovery of the native liver function., Recent Findings: Nonbiological devices such as molecular adsorbent recirculating system (MARS) and fractionated plasma separation and adsorption (Prometheus) are effective in improving severe hepatic encephalopathy and cholestasis, have good safety and tolerability profiles and are frequently employed in patients with ACLD; however, randomized controlled trials (RCTs) failed to show improvement in survival. Biologic devices that incorporate hepatic cells in bioreactors are also under development. Recent data from pilot studies suggested improvement in survival rates in some groups of patients with ACLF; however, their effect on patient survival in RCT is still unknown., Summary: Liver support systems are safe and well tolerated when used in management of patients with ACLF. Their use should continue in controlled clinical trials to explore their role in bridging patients to liver transplantation or recovery in well defined patient groups.

In the United States, Salmonella infections (salmonellosis) cause multiple medical problems. Although the most common presenting symptom is diarrhea, bacteremia can also occur. An estimated 1.4 million cases of salmonellosis occur annually in the United States. We present a case of Salmonella bacteremia in a 12-day old infant. We discuss the presenting signs, symptoms, and management strategies for a patient younger than 28 days old (neonate) presenting with fever and diarrhea.

Eosinophilic ascites (EA) is a rare disorder of unknown etiology that has been reported in both adult and pediatric patients. It is a part of the syndrome of eosinophilic gastroenteritis, which is characterized by eosinophilic infiltration of any or all layers of the gut wall and may involve any segment of the gastrointestinal tract. Peripheral eosinophilia may or may not be present. We report a case of EA that developed post partum.

Although an estimated 1 million persons in the United States are chronically infected with hepatitis B virus, the prevalence of hepatitis B has declined since the implementation of a national vaccination program. Hepatitis B virus is transmitted in blood and secretions. Acute infection may cause nonspecific symptoms, such as fatigue, poor appetite, nausea, vomiting, abdominal pain, low-grade fever, jaundice, and dark urine; and clinical signs, such as hepatomegaly and splenomegaly. Fewer than 5 percent of adults acutely infected with hepatitis B virus progress to chronic infection. The diagnosis of hepatitis B virus infection requires the evaluation of the patient's blood for hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody. The goals of treatment for chronic hepatitis B virus infection are to reduce inflammation of the liver and to prevent complications by suppressing viral replication. Treatment options include pegylated interferon alfa-2a administered subcutaneously or oral antiviral agents (nucleotide reverse transcriptase inhibitors). Persons with chronic hepatitis B virus infection should be monitored for disease activity with liver enzyme tests and hepatitis B virus DNA levels; considered for liver biopsy; and entered into a surveillance program for hepatocellular carcinoma.

Background: Currently, little evidence supports computer-based simulation for ERCP training., Objective: To determine face and construct validity of a computer-based simulator for ERCP and assess its perceived utility as a training tool., Design: Novice and expert endoscopists completed 2 simulated ERCP cases by using the GI Mentor II., Setting: Virtual Education and Surgical Simulation Laboratory, Medical College of Georgia., Main Outcome Measurements: Outcomes included times to complete the procedure, reach the papilla, and use fluoroscopy; attempts to cannulate the papilla, pancreatic duct, and common bile duct; and number of contrast injections and complications. Subjects assessed simulator graphics, procedural accuracy, difficulty, haptics, overall realism, and training potential., Results: Only when performance data from cases A and B were combined did the GI Mentor II differentiate novices and experts based on times to complete the procedure, reach the papilla, and use fluoroscopy. Across skill levels, overall opinions were similar regarding graphics (moderately realistic), accuracy (similar to clinical ERCP), difficulty (similar to clinical ERCP), overall realism (moderately realistic), and haptics. Most participants (92%) claimed that the simulator has definite training potential or should be required for training., Limitations: Small sample size, single institution., Conclusions: The GI Mentor II demonstrated construct validity for ERCP based on select metrics. Most subjects thought that the simulated graphics, procedural accuracy, and overall realism exhibit face validity. Subjects deemed it a useful training tool. Study repetition involving more participants and cases may help confirm results and establish the simulator's ability to differentiate skill levels based on ERCP-specific metrics.

Diverticular bleeding is a common cause of lower gastrointestinal hemorrhage. Patients typically present with massive and painless rectal hemorrhage. If bleeding is severe, initial resuscitative measures should include airway maintenance and oxygen supplementation, followed by measurement of hemoglobin and hematocrit levels, and blood typing and crossmatching. Patients may need intravenous fluid resuscitation with normal saline or lactated Ringer's solution, followed by transfusion of packed red blood cells in the event of ongoing bleeding. Diverticular hemorrhage resolves spontaneously in approximately 80 percent of patients. If there is severe bleeding or significant comorbidities, patients should be admitted to the intensive care unit. The recommended initial diagnostic test is colonoscopy, performed within 12 to 48 hours of presentation and after a rapid bowel preparation with polyethylene glycol solutions. If the bleeding source is identified by colonoscopy, endoscopic therapeutic maneuvers can be performed. These may include injection with epinephrine or electrocautery therapy. If the bleeding source is not identified, radionuclide imaging (i.e., technetium-99m-tagged red blood cell scan) should be performed, usually followed by arteriography. For ongoing diverticular hemorrhage, other therapeutic modalities such as selective embolization, intra-arterial vasopressin infusion, or surgery, should be considered.

Metastatic dissemination of primary tumors is responsible for 90% of colorectal cancer (CRC) deaths. The presence of positive lymph nodes, which separates stage I/II from stage III CRC, is a particularly key factor in patient management. Here, we describe results of a quantitative proteomic survey to identify molecular correlates of node status. Laser capture microdissection and two-dimensional difference gel electrophoresis were used to establish expression profiles for 980 discrete protein features in 24 human CRC specimens. Protein abundances were determined with a median technical coefficient of variation of 10%, which provided an ability to detect small differences between cancer subtypes. Transgelin, a 23-kDa actin-binding protein, emerged as a top-ranked candidate biomarker of node status. The area under the receiver operating characteristic curve for transgelin in predicting node status was 0.868 (P = .002). Significantly increased frequency of moderate- and high-level transgelin expression in node-positive CRC was also seen using semiquantitative immunohistochemistry to analyze 94 independent CRC specimens on tissue microarrays (P = .036). Follow-up studies in CRC cell lines demonstrated roles for transgelin in promoting invasion, survival, and resistance to anoikis. Transgelin localizes to the nucleus of CRC cells, and its sequence and properties suggest that it may participate in regulation of the transcriptional program associated with the epithelial-to-mesenchymal transition.

Although plasma cell infiltration is not rare in autopsy of patients with multiple myeloma (MM), it is very rarely detected in living patients. This is because MM rarely causes significant liver dysfunction that requires further evaluation. A 49-year-old man presented with acute renal failure and was diagnosed with kappa light chain MM stage IIB. Thalidomide and dexamethasone were initiated. The patient developed a continuous increase in bilirubin that led to severe cholestasis. A liver biopsy revealed plasma cell infiltration. He then rapidly progressed to liver failure and died. Treatment options are limited in MM with significant liver dysfunction. Despite new drug therapies in MM, those patients with rapidly progressive liver failure appear to have a dismal outcome.

Objectives: We performed a prospective study of asymptomatic adult volunteers to establish normative values of pharyngeal pH using a novel pH probe., Methods: The Dx-pH probe is a novel pH device capable of measuring liquid and aerosolized acid levels. Twenty asymptomatic patients (Reflux Symptom Index less than 10 and Reflux Finding Score less than 6) underwent simultaneous investigation with this probe placed in the oropharynx and a dual antimony probe placed in the hypopharynx and esophagus. The reflux parameters measured from the oropharyngeal probe included the percentage of time and the number of events in which the pH was less than 5.5,5.0,4.5, and 4.0., Results: The upper limits of normal (95th percentile) for the number of events below pH of 5.5, 5.0, 4.5, and 4.0 per 24-hour period were 16.6, 10.7, 7.4, and 0.2, respectively. The upper limits of normal (95th percentile) for an acid exposure time below pH of 5.5, 5.0, 4.5, and 4.0 per 24-hour period were 820 seconds, 385 seconds, 75 seconds, and 3 seconds, respectively., Conclusions: Normative pharyngeal pH values are presented. Further studies are required to determine clinical relevance.

Proteomics refers to the study of the entire set of proteins in a given cell or tissue. With the extensive development of protein separation, mass spectrometry, and bioinformatics technologies, clinical proteomics has shown its potential as a powerful approach for biomarker discovery, particularly in the area of oncology. More than 130 exploratory studies have defined candidate markers in serum, gastrointestinal (GI) fluids, or cancer tissue. In this article, we introduce the commonly adopted proteomic technologies and describe results of a comprehensive review of studies that have applied these technologies to GI oncology, with a particular emphasis on developments in the last 3 years. We discuss reasons why the more than 130 studies to date have had little discernible clinical impact, and we outline steps that may allow proteomics to realize its promise for early detection of disease, monitoring of disease recurrence, and identification of targets for individualized therapy.

Liver disorders associated with pregnancy include hyperemesis gravidarum (HG), intrahepatic cholestasis of pregnancy (ICP), preeclampsia, syndrome of hemolysis, elevated liver enzymes and low platelets (HELLP), and acute fatty liver of pregnancy (AFLP). These conditions are relatively common and unique to pregnancy and are more likely to occur at certain terms of gestation specific to each condition. They can be associated with significant maternal and fetal morbidity and mortality. Although managing such patients may be very challenging, spontaneous resolution of the disease occurs shortly after termination of the pregnancy, usually without hepatic sequellae. Early diagnosis and timely treatment is a key to therapeutic success. This article explores the clinical features, pathophysiology, and management of these disorders.

We present four cases of gastrointestinal granular cell tumors (GCT) with a literature review. Gastrointestinal granular cell tumors, a benign neural tumor thought to arise from Schwann cells, can occur in several areas, including the gastrointestinal tract. Studies suggest that endoscopic ultrasound and endoscopic removal is the treatment of choice for esophageal GCTs if they are small in size (< 2 cm) and do not involve the muscularis propria. GCTs are malignant less than 2% of the time. Although most GCTs are benign and can be followed endoscopically without resection, the malignant potential warrants evaluation with endoscopic ultrasound for possible endoscopic or surgical resection.

The incidence and prevalence of achalasia is 0.6/100,000 people per year and 1/10,000, respectively. It is difficult then for one center to accumulate a large cohort of patients. One study (Gut 33:1011,1992) described the presenting symptoms in only 38 patients. To approach this problem differently, we used the internet to access a larger patient population. Using search engines at Google and Yahoo, Inc., we identified achalasia support groups. We examined the most populated support group (YSG) and assembled the exchanged messages into 4 categories: support, symptoms, treatment, and diagnosis. Next, a survey modeled after a previous study (ibid) was composed and posted on a university-sponsored Web site for March 2003, advertised to YSG members, and then removed from the server. The results were entered into a database and analyzed. There were 6 support groups identified; 1 was foreign. The most populated site was the Yahoo, Inc., group with 298 active members. We analyzed the 3,222 messages posted from October 6, 2002 through October 5, 2003. The message composition was as follows: 67% support, 16% symptoms, 12% treatment, and 5% diagnosis. Of 298 Yahoo site members, we had 88 respondents to the survey from 9 countries. The data from 83 were analyzed (5 were not completed). Respondents were 66 women (55%), 29 men (24%), and 5 non-gender-identified respondents. They ranged in age from 6 to 72 years at time of diagnosis. In the 83 respondents, dysphagia symptoms were reported by 98%, regurgitation by 68%, chest pain by 81%, weight loss by 69%, and epigastric pain by 67%, similar to those reported in the study cited in Gut. The modalities used to evaluate these achalasia patients were as follows: 83% had monometry, 87% had radiography, and 89% had endoscopy. The mean time from symptom onset to diagnosis was 5 years. The treatments attempted on this population were balloon dilatation in 57%, botulinum toxin injection (Botox) in 8%, myotomy in 12%, by lifestyle/diet modification in 12%, and other treatments in 11%. We believe that the Internet can provide physician-researchers with useful information about common and uncommon diseases on a global basis. The Internet allows patients to voice concerns that they may not freely express to their doctor and provides a modality to collect data from a larger number of patients than may be available at any single institution.

Aim: To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database., Method: We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test., Results: Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients., Conclusion: HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.

Abdominal pain is a common presenting symptom in adults with sickle cell disease (SCD). One case of Helicobacter pylori gastritis has been reported in a child with sickle cell anemia. H. pylori-induced peptic ulcer disease (PUD) has not previously been reported in adults with SCD. We report eight cases of H. pylori infection in adult sickle cell patients presenting with acute or recurrent abdominal pain and/or gastrointestinal bleeding. In all cases, H. pylori serology (IgG) was positive, and three patients had gastric or duodenal ulcer by endoscopic examination. All patients responded to H. pylori treatment with complete resolution of symptoms by 4 weeks. The prevalence of H. pylori infection in SCD is unknown, but patients may be at increased risk for H. pylori-induced PUD and complications due to pre-existing anemia, increased nonsteroidal anti-inflammatory drug use, and alloimmunization which may delay necessary transfusion. It is important that the differential diagnosis of abdominal pain in adults with SCD include nonsickle cell-related disorders such as PUD. When confirmed, a definitive etiology of PUD must be determined so that appropriate treatment strategies can be initiated promptly and excess morbidity avoided.

The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy: age 35 years of more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 years of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (> of = 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T(1)) and 4 (T(4)) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based is 3 years (T(1) to T(4)), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T(1), given that at least 10-15% of polyps may be missed at baseline. The final (T(4)) colonoscopies are expected to be completed in early 1998.

Unlabelled: By conventional criteria the diagnosis of primary sclerosing cholangitis (PSC) is excluded if biliary tract calculi are present., Objective: To compare patients with sclerosing cholangitis with and without calculi., Methods: Retrospective review between 8/91 and 9/93 identified 63 patients with sclerosing cholangitis alone (Group A) and 22 patients with sclerosing cholangitis and biliary tract calculi (Group B). The mean follow-up was 13.6 months. Clinical features reviewed were age, sex, associated inflammatory disease (IBD), and clinical presentation. Cholangiographic features compared were site and extent of disease. Endoscopic stone extraction was reviewed for success and complications., Results: Both groups had the following features in common: 1) mean age (45.9 vs 46.3 yr), 2) prevalence of IBD (68.3 vs 72.7%), 3) extent of bile duct strictures (intrahepatic: 28.5% vs 27.2%; extrahepatic: 12.7% vs 13.6%; both: 58.7% vs 54.5%). There were proportionately more women in Group B (45.5% vs 33.3%). Symptomatic presentation (pain, pruritus, jaundice, and cholangitis) was seen more often in Group B: 86.4% compared with Group A: 39.7% (specifically cholangitis was seen in 22.7% vs 4.7%). Among Group B, calculi developed subsequent (mean 40.2 months) after the diagnosis of sclerosing cholangitis in 77.3% of patients. The distribution of calculi was cholelithiasis: 7 (31.8%); choledocholithiasis: 9 (40.9%); and both: 6 (27.2%). Of the patients with choledocholithiasis alone, 78% had undergone previous cholecystectomy. Endoscopic stone extraction was successful in 13 (86.6%) of the patients with choledocholithiasis. Complications included mild pancreatitis in one patient and bleeding from sphincterotomy site in another patient which responded to sclerotherapy. In follow-up, only one patient had recurrent calculi and underwent successful stone extraction., Conclusion: We suggest that biliary tract calculi are a part of the spectrum of otherwise typical PSC and therefore their presence should not necessarily exclude the diagnosis.

From January 1985 through July 1987, adult patients accepted for liver transplantation with large esophageal varices were enrolled in a study evaluating the use of prophylactic vs emergency sclerotherapy. Six hundred forty-eight subjects received prophylactic sclerotherapy, and 172 received emergent sclerotherapy. Esophageal stricture formation was increased 12.9-fold (P < 0.001), esophageal perforation 6.4-fold (P < 0.005), and postsclerotherapy bleeding esophageal ulcers 3.7-fold (P < 0.001) in those receiving emergency sclerotherapy as opposed to prophylactic sclerotherapy. These differences were even greater if the number of sclerotherapy sessions rather than the number of patients was used as the denominator for the comparisons. In total, 19.6% of emergency sclerotherapy cases were associated with an untoward outcome of sclerotherapy; only 1.9% of cases receiving prophylactic sclerotherapy experienced an untoward outcome (P < 0.001). These data demonstrate that emergency sclerotherapy is associated with a greater prevalence of complications and support earlier studies that show that sclerotherapy prevents variceal bleeding over the short term. The data also suggest that when applied to patients with large varices awaiting orthotopic liver transplantation, it enhances the chance of a patient surviving to be transplanted by preventing a variceal bleed and the spiral of liver failure and death that frequently follows an episode of acute variceal bleeding.

Gastrointestinal infection due to cytomegalovirus occurs frequently in liver transplant recipients. Upper gastrointestinal cytomegalovirus infection is associated with subjective complaints of nausea, a sense of abdominal fullness, and occasionally emesis and/or dysphagia. In order to determine whether these symptoms reflect a disruption of the normal motility of the stomach, the following study was performed. Eleven individuals who were evaluated for liver transplantation were prospectively recruited and studied as follows: (1) upper gastrointestinal endoscopy with biopsy of the gastric antral mucosa; (2) viral culture of the gastric mucosa; (3) a histologic examination of the gastric mucosa; and (4) a radionuclide gastric emptying study was obtained before and 4-8 weeks following successful liver transplantation. Prior to liver transplantation, none had symptoms of nausea, vomiting, or epigastric fullness. All were culture-negative for cytomegalovirus. All had endoscopic and histologic evidence of portal hypertensive gastropathy but none had antral erosions or ulcers. All demonstrated normal gastric emptying of a liquid meal. Following liver transplantation, 6 remained free of gastric cytomegalovirus while 5 developed a culture-confirmed gastric cytomegalovirus infection. Those that developed a gastric cytomegalovirus infection also had more gastric symptoms, and more gastric histologic abnormalities. Moreover, those with a gastric cytomegalovirus infection demonstrated enhanced gastric retention of a liquid meal (P less than 0.01).

A technique is described whereby it is possible to surgically ablate the lumbosacral spinal cord of a developing mouse fetus without interfering with fetal viability. The lumbosacral spinal cords of 14-day in utero, 129ReJ mice were ablated with a Cooper Nd-YAG laser, and the fetuses, enclosed in their membranes and attached to the uterus by their placentae, were allowed to develop in the abdominal cavity of the dam. The cytoarchitecture and the temporal pattern of organogenesis of aneural soleus muscles were studied in spaced, serial, transverse, ultrathin sections of muscles of 16- and 18-day gestation and newborn (20-day gestation) mice. At the time of surgery, the soleus muscle was a discrete mass consisting of primary myotubes and a pleomorphic population of mononucleated cells. Axon bundles and blood vessels were found at the muscle's periphery, but had not penetrated throughout the muscle mass. The organogenesis of the aneural muscle was remarkably similar to that of the innervated soleus muscle (Ontell et al., Am J Anat 181:267-278, 1988). In the aneural muscle, as in the innervated muscle, significant numbers of secondary myotubes formed all along the lengths of primary myotubes. Moreover, the time course of myotube formation, the dynamics of cluster formation and cluster dispersal, and the ultrastructural appearance of the myotubes mimicked that observed in innervated muscle. The frequency of necrotic myotubes was no greater in the aneural muscle than in the innervated soleus muscle. Myotube maturation was similar in aneural and innervated soleus muscles until 18 days gestation. However, at birth, aneural myotubes appeared to be slightly less mature than innervated myotubes. Thus, the major morphogenic phenomena that characterize the development of the soleus muscle appear to be independent of innervation.

Endoscopic retrograde cholangiopancreatography (ERCP) was performed 42 times in 38 patients aged 14 months to 20 yr at Children's Hospital of Pittsburgh from 1982 to 1990. The adult side-viewing duodenoscope, Olympus JF1T, was used for all procedures. Intravenous sedation was used in 68% of the patients, whereas general anesthesia was employed in the remainder. Visualization of the appropriate ductal system was accomplished in 35 patients (92%). No therapeutic maneuvers were performed at endoscopy. Eleven of the 22 patients with ductal abnormalities underwent surgical treatment, based on the ERCP findings. The only complication encountered was mild pancreatitis in three patients (8%), all with a history of pancreatitis. We conclude that ERCP is a safe, useful procedure in the evaluation of children with pancreaticobiliary disorders, and in the identification of surgically correctable lesions in 29% of those patients.

Individuals with chronic renal failure (CRF) may have a variety of gastrointestinal (GI) problems, including dyspepsia, acid peptic disease, and bacterial overgrowth. We investigated gastrointestinal function in 11 uremic patients, seven of whom were on dialysis three times a week and four who were not on dialysis. Ten normal subjects were studied as controls. The nutritional status of the patients did not differ from that of the control subjects. Seven patients demonstrated abnormal GI endoscopic findings, although none was severe; they also had prolonged oral-cecal transit times but had no evidence of bacterial overgrowth, and all had normal numbers of lymphocyte subpopulations within the intestinal mucosa. The patients had significantly reduced activities of mucosal sucrase and maltase but not of lactase. In spite of the reductions in these enzymatic activities, carbohydrate malabsorption was not evident in the CRF group, probably because of the vast reserve of the small intestine. No differences were noted between the groups in the activities of several intestinal peptidases. From these data, we concluded that GI function is essentially normal in patients with CRF and postulate that this normality, which is in contrast to previous findings, is related to recent advances in the clinical management of uremic patients.