Gastrointestinal problems in the chronically critically ill patient.

In summary, a variety of gastrointestinal processes may occur in the chronically critically ill patient population, usually as consequence of the primary systemic process. The clinical presentation is frequently nonclassic and there often is a substantial delay in diagnosis, resulting in increased morbidity and mortality.

Spleen size in health and disease: a sonographic assessment.

Ultrasonography was used to evaluate splenic size in normal patients as well as in patients with various clinical conditions. To express splenic size, a splenic volumetric index (SVI) was used. By grading the SVI on the basis of age and sex in normal patients, and in various diseases, characteristic distributions of SVI were obtained. Obtaining the SVI by the use of ultrasound appears to be a significant supplemental aid for evaluating spleen size, especially in patients whose spleens are not palpable.

Ultrasonic evaluation of portosystemic collateral circulation in portal hypertension.

The aim of the study was to evaluate portosystemic collateral circulation in relation to (1)individual etiological groups of portal hypertension., (2) Presence and size of esophageal varices, (3) esophageal sclerotherapy and (4) ascites. A prospective study of 101 patients of portal hypertension was carried out. Patients were divided into 4 etiological groups: Alcoholic cirrhosis (ALD) (38), Non-alcoholic cirrhosis (NALD) (35), non cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Esophageal varices were assessed and graded endoscopically into 3 categories: no varix, small varices and large varices. Evaluation of portosystemic collateral circulation, other than esophageal varices was done ultrasonically. "Other" portosystemic collaterals (lienorenal, gastrorenal, dilated paraumbilical and umbilical veins, paraduodenal and gall bladdes varices) were seen in 26 out of 101 patients and more commonly in the non-cirrhotic groups (50%) [NCPF: 57.14%, EHPVO: 42.86%] than in the cirrhotic group (16.44%) [ALD: 13.5%, NALD: 20%]. Gall bladder varices were the only form of ectopic (extra esophagogastric) varices visualised with an overall incidence of 3.96%. Collateral shunts were seen more frequently in patients without varices (100%), than in patients with small varices (34.88%) or large varices (7.84%), and in patients having undergone esophageal sclerotherapy (57.14%). Collateral circulation did not contribute to the development of ascites. 37 patients with ascites did not have collateral shunts. We conclude portosystmic circulation plays a decompressive role in portal hypertension and prevents formation of esophageal varices or prevents them from increasing in size. It is seen more frequently in noncirrhotic patients and in those having undergone sclerotherapy and does not contribute to development of ascites.

Significance of radioisotope bone marrow uptake on 99m technetium sulphocolloid scan in portal hypertension.

A prospective study of 101 consecutive patients of portal hypertension was carried out to study the possible relationships between bone marrow activity on 99m technetium labelled sulphocolloid scan and severity of liver disease, etiology of portal hypertension and cirrhosis, as well as presence and extent of collateral circulation, including esophageal varices. The patients were divided into 4 etiological groups: alcoholic cirrhosis (ALD), (38) non-alcoholic cirrhosis (NALD) (35) non-cirrhotic portal fibrosis (NCPF) (14) and extrahepatic portal vein obstruction (EHPVO) (14). Patients of cirrhosis were categorised according to modified Child-Pugh's classification. Esophageal varices were graded endoscopically as (1) no varix (2) small varices (< 5mm) (3) large varices (> 5mm). All patients underwent radionuclide imaging using 99m Technetium labelled sulphocolloid and bone marrow activity was studied. Evaluation of portasystemic collaterals was done ultrasonically. We found that 16.6%, 44.6% and 72.72% patients with Child A, B and C cirrhosis respectively, had increased marrow activity (p < 0.05). There was no significant difference between marrow activity of patients with ALD (52.6%) and NALD (40%). None of the non-cirrhotic patients demonstrated bone marrow uptake of radioisotope. There was no significant difference between bone marrow uptake presence of lienorenal collaterals and presence or size of esophageal varices. We thus conclude the bone marrow activity on radioisotope scanning depends only on the severity of liver disease and does not vary a according to the etiology of cirrhosis, or presence and extent of portasystemic collaterals, including esophageal varices.

Systematic review: the quality of the scientific evidence and conflicts of interest in international inflammatory bowel disease practice guidelines.

BACKGROUND: Guidelines published by the international gastroenterology societies establish standards of care and seek to improve patient outcomes. AIM: We examined inflammatory bowel disease guidelines (IBD) for quality of evidence, methods of grading evidence and conflicts of interest (COI). METHODS: All 182 guidelines published by the American College of Gastroenterology, American Gastroenterological Association, British Society of Gastroenterology, Canadian Association of Gastroenterology, Crohn's and Colitis Foundation of America and European Crohn's and Colitis Organisation as of 27 September 2012 were reviewed. Nineteen IBD guidelines were found. RESULTS: Eighty-nine per cent (n = 17/19) of the guidelines graded the levels of evidence using seven different systems. Of the 1070 recommendations reviewed, 23% (n = 249) cited level A evidence; 28% (n = 302) level B; 36% (n = 383) level C and 13% (n = 136) level D. The mean age of the guidelines was 4.2 years. In addition, 61% (n = 11/19) of the guidelines failed to comment on COI. All eight articles commenting on COI had conflicts with 81% (n = 92/113) of authors reported an average 11.7 COI. Lastly, there were variations in the recommendations between societies. CONCLUSIONS: Nearly half the IBD guideline recommendations are based on expert opinion or no evidence. Majority of the guidelines fail to disclose any COI, and when commenting, all have numerous COI. Furthermore, the guidelines are not updated frequently and there is a lack of consensus between societal guidelines. This study highlights the critical need to centralize and redesign the guidelines development process.

Nonalcoholic steatohepatitis.

OBJECTIVE: To determine the clinical relevance of nonalcoholic steatohepatitis (NASH) and to review the available literature on the epidemiology, clinical features, histology, pathogenesis, clinical course, and management of this condition. DATA SOURCES: Pertinent articles in English identified through a MEDLINE search (1966 to the present) and the bibliographies of relevant articles. STUDY SELECTION: All studies, including case reports, evaluating the salient features and clinical profile of NASH. DATA EXTRACTION: Data were selected from all articles that fit the study selection criteria. DATA SYNTHESIS: Nonalcoholic steatohepatitis is a distinct clinical entity characterized by elevated plasma liver enzyme levels and liver biopsy findings that are identical to those seen in alcoholic hepatitis; patients with NASH, however, do not consume alcohol in quantities known to cause liver injury. Patients with NASH are typically obese, middle-aged women with asymptomatic hepatomegaly who are diabetic or hyperlipidemic and present with an unrelated medical problem. Analysis of liver biopsy specimens is the cornerstone of diagnosis; hepatic morphologic findings range from mild fatty degeneration and inflammation to cell degeneration, fibrosis, and cirrhosis with or without the presence of Mallory hyaline bodies. Elevated levels of free fatty acids in the liver are thought to be responsible for the development of steatohepatitis. Although NASH is most often a benign disease with an indolent course, patients with this condition occasionally develop cirrhosis, portal hypertension, and hepatic failure. In some cases, NASH may be reversed with weight reduction. CONCLUSION: Nonalcoholic steatohepatitis is an important differential diagnosis for asymptomatic patients with chronically elevated plasma liver enzyme levels, especially if obesity, diabetes, or hyperlipidemia are present. Analysis of liver biopsy specimens is necessary for diagnosis and must be done in all patients with unexplained abnormal liver function and negative results on a noninvasive workup. Prognosis is good in most patients. The precise role of weight reduction and ursodeoxycholic acid therapy in the favorable alteration of the natural history of this disorder needs to be addressed in large, well-controlled studies.

AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection.

OBJECTIVE: A liver biopsy is necessary to grade and stage chronic hepatitis C virus (HCV) infection. In a previous study of patients with nonalcoholic liver disease, an aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio >1 suggested cirrhosis. We sought to examine the value of the AST/ALT ratio in distinguishing cirrhotic patients with chronic HCV infection from noncirrhotic patients and to correlate the ratio with the grade and stage of hepatitis and other biochemical indices. METHODS: We retrospectively studied 139 patients with chronic HCV infection. Routine biochemical indices were determined, and the histological grade of necroinflammatory activity and the stage of fibrosis of the liver biopsy specimens were scored. RESULTS: The mean AST/ALT ratio in the cirrhotic patients (n = 47) was higher than in the noncirrhotic patients (n = 92) (1.06 +/- 0.06 vs 0.60 +/- 0.09; p < 0.001). A ratio > or =1 had 100% specificity and positive predictive value in distinguishing cirrhotic from noncirrhotic patients, with a 53.2% sensitivity and 80.7% negative predictive value. The ratio correlated positively with the stage of fibrosis but not with the grade of activity or other biochemical indices. Of the cirrhotic patients, 17% had no clinical or biochemical features suggestive of chronic liver disease except for an AST/ALT ratio > or =1. CONCLUSION: The AST/ALT ratio is a dependable marker of fibrosis stage and cirrhosis in patients with chronic HCV infection.

Evaluation of splenomegaly in portal hypertension.

Splenomegaly is obvious in portal hypertension, but controversy still exists over the relationship between splenic size or size of esophageal varices. Previous methods to assess spleen size are less accurate than ultrasonic estimation of spleen size by splenic volumetric index (SVI). In a prospective study, we evaluated 101 consecutive patients with portal hypertension for spleen size measured ultrasonically by SVI, presence and size of esophageal varices, and etiology of portal hypertension. A total of 219 age-matched controls were evaluated ultrasonically to define a normal SVI. Splenomegaly defined by 1 or 2 standard deviations of normal SVI had high accuracy in predicting portal hypertension, presence of esophageal varices, and provided a clue to the etiology of portal hypertension. However, there was no correlation between spleen size and size of esophageal varices.

Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10-7 cm2/hr to 120 x 10-7 cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphene sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.

Use of synthetic polypeptides in the preparation of biodegradable delivery vehicles for narcotic antagonists.

Synthetic polypeptides consisting of copolymers of glutamic acid and leucine have been shown to be useful materials for the fabrication of practical, biodegradable delivery vehicles for narcotic antagonists. Model delivery vehicles in film form were prepared from copolymers containing 10 mole percent to 40 mole percent glutamic acid, and loaded with 10% to 40% naltrexone by weight. The naltrexone was found to be released by diffusion, exhibiting diffusion coefficients that varied as a function of the glutamic acid content and the initial naltrexone loading. A wide range in diffusion coefficients were achieved (0.31 x 10(-7) cm2/hr to 120 x 10(-7) cm2/hr), leading to release rates within practical ranges of interest for meeting the program goals. We have demonstrated that the polypeptides can be fabricated into dosage forms that are amenable to administration by trochar. For example, rods 0.4 mm to 0.8 mm in diameter containing as much as 40% naltrexone by weight were extruded using a simple compression mold and die arrangement. An in vitro evaluation of the rods showed that antagonist is released by diffusion at a continuously decreasing rate, a behavior similar to that observed with the film devices that were, nonetheless, capable of blocking an AD80 challenge of morphine sulfate in mice for more than 30 days. One of the most promising delivery vehicles that we have developed to date consists of a polypeptide tube filled with a naltrexone/polypeptide core. Preliminary experiments have shown that these devices may be capable of administering high, constant rates of release for prolonged periods of time. Additional work, however, is required to develop techniques for the preparation of reproducible delivery vehicles.