Showing papers in "Digestive Diseases and Sciences in 1995"

Chronic pancreatitis caused by an autoimmune abnormality : proposal of the concept of autoimmune pancreatitis

Abstract: Several authors have reported a case of chronic pancreatitis associated with Sjogren's syndrome in which an autoimmune mechanism may have been involved in the etiology and in which steroid therapy was effective. We recently encountered a patient with pancreatitis who had hyperglobulinemia, was autoantibody-positive, and responded to steroid therapy. This patient, however, failed to show any evidence of association with Sjogren's syndrome or other collagen diseases. Although the concept of autoimmune hepatitis and the criteria for diagnosing it have been established, autoimmune pancreatitis has not yet been defined as a clinical entity. We report a case of chronic pancreatitis in which an autoimmune mechanism is involved in the etiology and summarize the cases of pancreatitis suspected of being caused by an autoimmune mechanism in the Japanese and English literature.

Functional bowel disorders - A multicenter comparison of health status and development of illness severity index

Abstract: In a multicenter study of patients with painful functional bowel disorders (FBD), we compared the demographic, health status, and diagnostic features of patients with FBD and developed a functional bowel disorder severity index (FBDSI) for research and clinical care. Two hundred seventy patients with FBD in the United States, England, and Canada were surveyed on symptoms and health status, and their physicians made a diagnosis and rated illness severity as mild, moderate, or severe. Comparisons of 22 demographic and clinical variables were made by study site in addition to physicians' severity ratings. To develop the FBDSI, multiple regression analysis used the demographic and clinical variables to predict the physician's rating of severity. We found that most health status measures of patients with FBD across study sites are comparable and the derived and validated FBDSI scoring system uses three easy to obtain variables: FBDSI = [current pain by visual analog scale (0-100)] + [diagnosis of chronic functional abdominal pain (0 if absent and 106 if present)] + [number of physicians visits over previous six months x 11]. The FBDSI can be used to select patients for research protocols and/or follow their clinical outcome or response to treatments over time.

Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey.

Abstract: The prevalence of fatty liver in children is unknown and its relationship to obesity is poorly defined. The present study of 810 northern Japanese children (4-12 years old) determined the prevalence of fatty liver in the pediatric population and its relationship to obesity. Diagnosis of fatty liver was based on established real-time ultrasonographic criteria. The overall prevalence of fatty liver was 2.6% and was higher for boys (3.4%) than for girls (1.8%), although not statistically significant (P = 0.15). Fatty liver was found in children as young as 6 years of age. There was no significant association between the prevalence of fatty liver and height (physical growth). There was a strong positive correlation between fatty liver prevalence and established obesity indices: Rohrer's Index--chi 2 linear trend = 59.2, P < 0.0001; body mass index--chi 2 linear trend = 91.6, P < 0.0001; and age-gender-adjusted Japanese standard index of weight for height--chi 2 linear trend = 93.2, P < 0.0001. However, direct measurement of abdominal subcutaneous fat thickness by ultrasonography was the best predictor of fatty liver: chi 2 linear trend = 159, P < 0.0001. These results indicate that fatty liver may develop very early in life, and there is a direct relationship between degree of obesity and fatty liver in children.

Small bowel bacterial overgrowth in patients with alcoholic cirrhosis

Abstract: A total of 89 patients with alcoholic cirrhosis and 40 healthy subjects were included in a study to assess the prevalence of intestinal bacterial overgrowth and to analyze its relationship with the severity of liver dysfunction, presence of ascites, and development of spontaneous bacterial peritonitis (SBP). Bacterial overgrowth was measured by means of a breath test after ingestion of glucose. Intestinal bacterial overgrowth was documented in 27 (30.3%) of the 89 patients with alcoholic cirrhosis and in none of the healthy subjects. The prevalence of intestinal bacterial overgrowth was significantly higher in cirrhotics with ascites (37.1%) than in those with no evidence of ascites (5.3%) and among patients with Pugh-Child class C (48.3%) than in patients with class A (13.1%) or B (27%). Twelve (17.1%) of the 70 patients with ascites developed an episode of SBP. The prevalence of spontaneous bacterial peritonitis was significantly higher in patients who had intestinal bacterial overgrowth (30.7%) than in patients who did not (9.09%). We conclude that intestinal bacterial overgrowth occurs in approximately one third of patients with cirrhosis secondary to alcohol, particularly in patients with ascites and advanced liver dysfunction. Moreover, bacterial overgrowth may be a condition favoring infection of the ascitic fluid.

Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity.

Abstract: Alteration in visceral sensation locally at the site of presumed symptom origin in the gastrointestinal tract has been proposed as an important etiopathological mechanism in the so-called functional bowel disorders. Patients presenting with one functional gastrointestinal syndrome, however, frequently have additional symptoms referable to other parts of the gut, suggesting that enhanced visceral nociception may be a panintestinal phenomenon. We measured the sensory thresholds for initial perception (IP), desire to defecate (DD), and urgency (U) in response to rectal balloon distension, and the thresholds for initial perception and for discomfort in response to esophageal balloon distension in 12 patients with irritable bowel syndrome (IBS) and 10 patients with functional dyspepsia (FD), in comparison with healthy controls. As expected, IBS patients exhibited lower rectal sensory thresholds than controls (P<0.0001), but in addition had significantly lower sensory thresholds for both perception and discomfort evoked by balloon distension of the esophagus (mean ±SEM: 8.8±1.3 ml vs 12.1±1.5 ml (P<0.05) and 12.2±1.4 ml vs 16.4±1.4 ml (P<0.02) respectively. Patients with FD showed similarily enhanced esophageal sensitivity, with thresholds for perception and discomfort of 8.1±0.9 ml (P<0.02), and 10.1±1.0 ml (P<0.001), respectively, but were also found to have sensory thresholds for rectal distension similar to those observed in the IBS group, significantly lower than in controls: IP 45.0±17.6 vs 59.3±1.5 ml (P<0.001), DD 98.0±17.9 vs 298.7±9.0 ml (P<0.0001), U 177.2±25.4 vs 415.1 ±12.6 ml (P<0.0001). Somatic nerve sensory thresholds showed no significant differences between the patient and control groups. Our findings indicate that alterations in visceral sensitivity in functional gastrointestinal disease affect sites in the gut other than the putative organ of symptom origin, supporting the concept of generally enhanced visceral awareness in patients with functional bowel disorders.

Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans.

Abstract: There is evidence that the distal intestine participates in the regulation of gastric motor and secretory function. It was the aim of this study to examine in greater detail the effects of ileal nutrient exposure on human gastric acid secretion and to investigate potential intermediary mechanisms. Twelve normal subjects were intubated with an oroileal multilumen tube assembly for gastric, duodenal, and ileal perfusion of marker and test solutions, aspiration, and intestinal manometry. We studied ileal effects on gastric acid output in the unstimulated, interdigestive state (during early phase II, N = 6), and during endogenous stimulation by intraduodenal essential amino acid perfusion, N = 6) and on release of candidate humoral mediators, peptide YY (PYY) and glucagonlike peptide-1 (GLP-1), both known inhibitors of human gastric acid secretion. Compared with ileal saline perfusion, ileal carbohydrate (total caloric load: 60 kcal) decreased interdigestive gastric acid output by 64% (P < 0.01), and endogenously stimulated output by 68%, respectively (P < 0.005). Under all experimental conditions, ileal carbohydrate increased plasma GLP-1 by 80-100% (all P < 0.005). Ileal lipid perfusion had similar inhibitory effects on gastric acid output and stimulatory effects on GLP-1 release as had ileal carbohydrate. By contrast, ileal perfusion with peptone had no or only weak effects on either acid output or plasma GLP-1. Plasma PYY concentrations and suppression of gastric secretion in response to ileal perfusions were not correlated. In humans, both interdigestive and endogenously stimulated gastric acid output are inhibited in response to intraileal carbohydrate or lipids, but not protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum interleukin-6, interleukin-8, and beta 2-microglobulin in early assessment of severity of acute pancreatitis. Comparison with serum C-reactive protein.

Abstract: The aim of this study was to compare the sensitivity, specificity, and diagnostic accuracy of serum interleukin-6, interleukin-8,β2-microglobulin, and C-reactive protein in the assessment of the severity of acute pancreatitis using commercial kits for their respective assays. Thirty-eight patients with acute pancreatitis (25 men, 13 women, mean age 59 years, range 16–97) were studied; the diagnosis was based on prolonged upper abdominal pain associated with a twofold increase of serum lipase, and it was confirmed by imaging techniques. According to the Atlanta criteria, 15 patients had severe illness and 23 had mild disease. The four serum markers were determined in all patients on admission, as well as daily for the following five days. On the first day of the disease, the sensitivity (calculated on patients with severe pancreatitis), specificity (calculated on patients with mild pancreatitis), and the diagnostic accuracy of these serum markers for establishing the severity of acute pancreatitis were 100%, 86%, and 91% for interleukin-6 (cutoff level 2.7 pg/ml); 100%, 81%, and 88% for interleukin-8 (cutoff level 30 pg/ml); 58%, 81%, and 73% forβ2-microglobulin (cutoff level 2.1 mg/liter); and 8%, 95%, and 64% for C-reactive protein (cutoff level 11 mg/dl). The results of our study indicate that, when assayed during the first 24 hr of disease onset, interleukin-6 and interleukin-8 are better markers thanβ2-microglobulin or C-reactive protein for evaluating the severity of acute pancreatitis.

Papillary dilation vs sphincterotomy in endoscopic removal of bile duct stones. A randomized trial with manometric function.

Abstract: To circumvent the long-term effects of papillary ablation for extracting common bile duct stones (< 12 mm in diameter) in endoscopic sphincterotomy (EST), endoscopic papillary dilation (EPD) was attempted in 20 patients. To evaluate papillary function before and after the procedures, manometry of the sphincter of Oddi was carried out in 13 with EPD and 10 of 20 patients with EST. Extraction of all stones was successful (100%) in both groups at an equal rate. Repeated numbers of procedures were common in both groups. However, the mean duration of the procedure was high in EPD compared to EST (63 min vs 42 min, P < NS). Adjunctive therapies like mechanical lithotripsy (ML), nasobiliary drainage, and choledochoscopy were included in EPD, while EST required a basket catheter and ML. There was no significant difference on manometry before and after the procedures (P = NS), although papillary function was found to have decreased after the EPD. In contrast, all patients in the EST group lost papillary function after the procedure. Thirty-day morbidity and mortality rate were absent in both groups. Immediate and 2.5-year follow up complications were uncommon in both groups. As a simple method, EPD may be an effective and safe alternative to EST in the management of patients with bile duct stones who require maintenance of papillary function.

Prospective evaluation of gastrointestinal tract in patients with iron-deficiency anemia

Abstract: Gastrointestinal bleeding is believed to cause iron-deficiency anemia (IDA). The information concerning ideal evaluation of the gastrointestinal tract and exact findings in patients with IDA is scant. The aim of this study was to prospectively evaluate patients with IDA for gastrointestinal lesions potentially causing IDA at a US Army Teaching Medical Center with Gastroenterology Fellowship. Seventy patients with IDA had esophagogastroduodenoscopy (EGD) and colonoscopy, and if this evaluation was unremarkable, then small bowel biopsy was obtained at EGD to evaluate for celiac disease. Enteroclysis was done if endoscopic evaluation was negative. At endoscopy, at least one lesion potentially accounted for the IDA in 50 (71%) patients. At colonoscopy, 21 (30%) patients had 22 lesions (four colon cancer, seven adenoma > 1 cm, six vascular malformation, four severely bleeding hemorrhoids, one ileal Crohn's); at EGD, 39 (56%) patients had 43 lesions (11 gastric erosion, 10 esophagitis, four vascular malformation, four celiac disease, three gastric cancer, three gastric ulcer, three duodenal ulcer, two gastric polyp > 1 cm, one duodenal lymphoma, one esophageal cancer, and one duodenal Crohn's). Twelve (17%) patients had both upper and lower gastrointestinal tract lesions. Twenty-four of 32 (75%) patients with positive fecal occult blood test had potentially bleeding lesions compared to 24 of 38 (63%) patients with negative fecal occult blood test (P > 0.05). Six of nine patients with malignancy had positive fecal occult blood test. Twenty patients with normal endoscopy and small bowel biopsy had normal enteroclysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of octreotide and erythromycin on idiopathic and scleroderma-associated intestinal pseudoobstruction.

Abstract: Treatment of chronic intestinal pseudoobstruction with prokinetic agents has been disappointing. Our study was designed to determine if octreotide and erythromycin would provide sustained relief from nausea, abdominal pain, and bloating in pseudoobstruction. Using gastrointestinal manometry, quantitative parameters of the activity front of the migrating motor complex at baseline and after prokinetic therapy with erythromycin and octreotide were determined in 14 patients with intestinal pseudoobstruction who had nausea, abdominal pain, and bloating. Patients were treated with erythromycin and octreotide for 20–33 weeks. Octreotide increased the frequency, duration, and motility index of activity fronts (AFs) from 1.2±0.3 AFs/4hr, 2.7±0.7 min, and 85±23 min mm Hg to 4.1±0.8 AFs/4 hr, 5.5±0.7 min, and 152±24 min mm Hg, respectively (P<0.05). Antral activity was decreased from 63±14 to 23±8% by octreotide (P<0.05). Erythromycin induced antral activity; however, small intestinal motor activity was suppressed. While on erythromycin and octreotide, five patients had long-term improvement of nausea and abdominal pain. All responders had at least 5 AFs/4 hr induced by octreotide. We conclude that octreotide and erythromycin relieve abdominal pain and nausea in pseudoobstruction. Patients who have at least 5 AFs/4 hr after octreotide administration are most likely to clinically respond.

Autoimmune cholangitis: a variant of primary biliary cirrhosis. Clinicopathologic and serologic correlations in 200 cases.

Abstract: The term “autoimmune cholangitis” is used for a disease with clinical and pathologic features of primary biliary cirrhosis (PBC) but with negative anti-mitochondrial antibody (AMA) and positive anti-nuclear antibody (ANA) tests. In order to characterize autoimmune cholangitis and to determine whether this truly differs from PBC, we reviewed 200 cases morphologically consistent with PBC in which data on AMA and ANA status were available to us. Of these, 64 (32%) had a negative AMA, 114 (57%) had a positive ANA, and 40 (20%) had negative AMA and positive ANA (autoimmune cholangitis). The AMA-negative group was slightly younger on average (50 vs 55 years) than AMA positives (P<0.05). There were no significant differences in gender (15.5% male overall), hepatic histopathology, or other laboratory tests between the groups of patients with any of the 4 possible combinations of AMA and ANA. Since the only consistently distinguishing feature among these patients is the autoantibody (AMA and ANA) profile, and they otherwise have virtually identical clinical and histopathologic features, autoimmune cholangitis can be considered to be the same as AMA-negative PBC.

Visceral perception in irritable bowel syndrome : rectal and gastric responses to distension and serotonin type 3 antagonism

Abstract: We wished to determine if visceral perception in the rectum and stomach is altered in patients with irritable bowel syndrome and to evaluate the effects on visceral sensation of 5-HT3 receptor blockade. Twelve community patients with diarrhea-predominant irritable bowel syndrome and 10 healthy controls were studied in a double-blind, randomized, placebo-controlled study. Using two barostats, the stomach and rectum were distended, with pressure increments of 4 mm Hg, from 10 to 26 mm Hg; visceral perception was measured on an ordinal scale of 0–10. Personality traits were measured using standard psychological methods, and somatic pain was evaluated by immersion of the nondominant hand in cold water. The effect of 5-HT3 antagonism was tested with a single intravenous dose of ondansetron at 0.15 mg/kg. Gastric perception was higher in irritable bowel syndrome, but rectal distension was perceived similarly in irritable bowel syndrome and controls. Pain tolerance to cold water was also similar in irritable bowel syndrome and controls. Ondansetron induced rectal relaxation and increased rectal compliance but did not significantly alter gastric compliance or visceral perception. Psychological test scores were similar in patients and controls. We conclude that in this group of psychologically normal patients with irritable bowel syndrome, who were not chronic health-care seekers, visceral perception was normal. Ondansetron did not alter gut perception in health or in irritable bowel syndrome.

Irritable bowel syndrome defined by factor analysis. Gender and race comparisons.

Abstract: To examine the applicability across subgroups of the Manning criteria commonly used to diagnose the irritable bowel syndrome, a 22-item symptom questionnaire was administered to male and female African-American and Caucasian adults (N=1344). Principal components factor analysis with varimax rotation was used to identify symptom clusters. Consistent with the findings of a previous factor analytic study, three of the six Manning symptoms (loose stools and more frequent bowel movements with onset of pain, pain relieved by defecation) formed a cluster corresponding to the irritable bowel syndrome in all subgroups. It is concluded that: (1) The three core Manning symptoms have equal applicability to both genders and to African-Americans as well as to Caucasians. They are useful symptom criteria for the diagnosis of IBS when used in conjunction with medical evaluation. (2) Three of the six Manning symptoms rarely correlate with the others; if confirmed in patient samples, this would indicate that these three symptoms are not useful for making a diagnosis of the irritable bowel syndrome.

Impact of functional dyspepsia on quality of life

Abstract: Little information on functional status and well-being is available in patients with functional gastrointestinal disease. We aimed to evaluate whether quality of life is poorer in patients with functional dyspepsia. A consecutive sample of 73 patients with functional dyspepsia completed a validated questionnaire prior to endoscopy. Organic disease controls comprised 658 outpatients attending endoscopy. Quality of life was measured using the validated Medical Outcomes Survey (which assessed physical, role, and social functioning; mental health; health perception; and any bodily pain) and the Brief Symptom Inventory (for current anxiety and depression); additional specific gastrointestinal items were also included. A stepwise logistic regression analysis was used to assess the association between diagnostic group and the quality of life measures, adjusting for potential confounders. Patients who reported more interruptions in their daily activities due to abdominal pain and who had fewer limitations of physical functioning were more likely to have functional dyspepsia (vs other disease,P<0.01). Mental health, social functioning, and health perception also tended to be poorer in functional dyspepsia. We conclude that quality of life may be more impaired in patients with functional dyspepsia than in patients with other conditions, who present for upper endoscopy.

Nonsteroidal antiinflammatory drugs and dyspepsia in the elderly

Abstract: Upper gastrointestinal tract symptoms are common in the elderly and, despite a paucity of data, nonsteroidal antiinflammatory drugs (NSAIDs) are believed to be important risk factors. We aimed to evaluate the association of NSAIDs with dyspepsia and heartburn in a population-based study. An age- and gender-stratified random sample of Olmsted County, Minnesota, Caucasian residents aged 65 years and older was mailed a valid self-report questionnaire; 74% responded (N=1375). Age- and gender-adjusted (to 1980 US Caucasian population) prevalence rates for NSAID use, dyspepsia (defined as pain located in the upper abdomen or nausea), and heartburn (defined as retrosternal burning pain) were calculated. Logistic regression analysis was used to estimate the association of dyspepsia and heartburn with potential risk factors adjusting for age and gender. The age- and gender-adjusted annual prevalences (per 100) of aspirin and nonaspirin NSAID use were 60.0 (95% CI 57.2,62.7) and 26.1 (95% CI 23.6,28.7), respectively. The annual prevalences of dyspepsia and heartburn were 15.0 (95% CI 12.9,17.0) and 12.9 (95% CI 10.9,14.8), respectively. Aspirin was associated with dyspepsia and/or heartburn (OR=1.6, 95% CI 1.2,2.2) as were nonaspirin NSAIDs (OR=1.8, 95% CI 1.3,2.6), but smoking and alcohol were not significant risk factors. Aspirin and nonaspirin NSAIDs are associated with almost a twofold risk of upper gastrointestinal tract symptoms in elderly community subjects.

Prothrombotic state and signs of endothelial lesion in plasma of patients with inflammatory bowel disease

Abstract: Recent investigations suggest that microthrombi formation in bowel capillaries could be a determinant factor in inflammatory bowel disease (IBD) pathogenesis. To evaluate the implication of the hemostatic system during these thrombotic events, we analyzed plasmatic values of prothrombotic state markers, physiologic inhibitors of coagulation, and endothelial lesion markers in 112 IBD patients. We found an increase in thrombin-antithrombin complexes and a decrease in antithrombin III, probably due to consumption, demonstrating an increase in thrombin generation. High levels ofd-dimer reflect increased fibrin formation, but there is no correlation between thrombin generation markers andd-dimer, possibly suggesting the presence of inadequate fibrinolysis. Levels of tissue factor pathway inhibitor were higher in patients than in controls. Nine patients with Crohn's disease (35% of our sample) had levels of this marker under 70% (range 37–69%). Von Willebrand factor values were increased and those of thrombomodulin only in active patients. Most of the changes were detected in patients with inflammatory activity, and there were no differences between ulcerative colitis and Crohn's disease. In conclusion, these results support the hypothesis that there is an endothelial lesion with sustained coagulation activation in IBD patients.

Efficacy of peripheral kappa agonist fedotozine versus placebo in treatment of irritable bowel syndrome. A multicenter dose-response study.

Abstract: The efficacy and safety of the peripheral kappa agonist fedotozine was evaluated in a double-blind, multicenter study involving 238 patients with the irritable bowel syndrome. After a two-week washout, patients were assigned to one of four groups to receive either placebo or fedotozine three times a day at doses of 3.5, 15, or 30 mg for six weeks. Patient assessment of mean symptom intensity indicated that the 30-mg dose of fedotozine was superior to placebo in relieving maximal daily abdominal pain (P=0.01), mean daily pain (P=0.007), and abdominal bloating (P=0.02). Changes in bowel function and defecation disorders could not be evaluated reliably. According to the investigators, the highest dose of fedotozine markedly reduced overall disease severity (P=0.003) and the pain component of the symptomatic profile (P=0.009). Clinical and laboratory safety was very good. Fedotozine 30 mg three times a day therefore appears to be effective and safe in the treatment of the abdominal pain and bloating associated with IBS.

Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent

Abstract: Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD specimens exhibited significantly higher IL-6 activity than control specimens in both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal tissues with an increased number of IL-6-producing cells. However, the activity in inactive IBD or inflammatory controls did not differ from controls. Northern blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial cells isolated from active IBD specimens but not in control cells. Furthermore, immunofluorescent microscopic study of active IBD specimens showed more conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and colonic epithelial cells. These results suggest that elevation of local IL-6 activity may be a characteristic feature of active IBD and both macrophages and colonic epithelial cells are the major cell types responsible for this phenomenon.

Long-term prospective study of Helicobacter pylori in nonulcer dyspepsia.

Abstract: Helicobacter pylori is present in up to 87% of patients with nonulcer dyspepsia. This study assessed the effect of eradicatingHelicobacter pylori infection on the symptoms of nonulcer dyspepsia at four weeks and one year after treatment. Dyspepsia was assessed on the frequency and severity of six symptoms [epigastric pain (night and day), nausea and vomiting, upper abdominal discomfort, and regurgitation] where each symptom was scored from 0 to 4.Helicobacter pylori status was assessed before treatment and four weeks after treatment with histology and microbiology, and at one year with a carbon-13 urea breath test. Eighty-three patients (23 males, 60 females; mean age 56.3 years; mean symptom duration 3.6 months) with nonulcer dyspepsia andHelicobacter pylori infection entered the study. Seventy-five were available at one year follow-up. Four weeks after treatment, the mean symptom score improved in those with eradication (6.95–2.3,P=0.01,N=41) or persistent infection (6.69–3.0,P=0.015,N=42). At one year, those with persistentHelicobacter pylori infection (N=38, score 5.24) had a higher score than those remaining clear of infection (N=24, score 1.4,P<0.0001) and those with reinfection (N=13, score 2.2,P<0.0001). In addition, persistentHelicobacter pylori infection was associated with more additional treatments than those with eradication (34/38 versus 4/37,P<0.001). These results suggest thatHelicobacter pylori plays an important role in the symptoms of nonulcer dyspepsia.

Autoimmune hepatitis. Evolving concepts and treatment strategies.

Abstract: Autoimmune hepatitis is an unresolving inflammation of the liver that is characterized by hypergammaglobulinemia, autoantibodies in serum, and the presence of at least periportal hepatitis (piecemeal necrosis) on histological examination (1). Now in its fifth decade of formal existence, autoimmune hepatitis is the archetypical form of chronic hepatitis (2, 3) and yet it is the least well understood (4, 5). Its autoimmune nature has been easier to presume than to prove (5), and its validity continues to be challenged by studies that implicate viruses and drugs as causative agents (6, 7). The concept that autoimmunity per se is a sufficient etiological basis for the disease is still heretical in some circles and, in the absence of pathognomonic features, pathogenic autoantibodies, well-characterized target autoantigens, clearly defined immunological mechanisms, and a reproducible animal model, it has been impossible to validate the disease (5). Fortunately, advances in molecular biology and the development of sensitive and specific diagnostic assays for viral infection have now afforded opportunities never before realized to solidify the concept of autoimmune hepatitis. The disease that had previously been shaped by deduction, exclusion, and loose association is at last acquiring a believable substantive character. Investigative activity has been intense, and traditional concepts about autoimmune hepatitis are rapidly changing. The nomenclature and diagnostic criteria have been standardized; homogeneous subpopulations of patients are being defined to facilitate assessment of pertinent pathogenic mechanisms; autoantibodies are being characterized to identify target autoantigens; candidate hepatic autoantigens

Compliance of the proximal stomach and dyspeptic symptoms in patients with type I diabetes mellitus

Abstract: In the present study the function of the proximal stomach and its role in eliciting dyspeptic symptoms were evaluated in patients with diabetes mellitus. Eight type I diabetics with cardiovascular autonomic neuropathy and dyspeptic symptoms, and 10 healthy volunteers were studied using an electronic barostat device connected to a intragastric bag. The intragastric bag was inflated and deflated by stepwise pressure increments, creating pressurevolume curves. During the experiment the blood glucose concentrations were maintained within the euglycemic range in the diabetics. The volume-pressure curves showed a larger volume during the pressure increase in the diabetics than in the controls (P<0.01). This resulted in a significant difference in compliance (dV/dP), 57.2±4.2 ml/mm Hg in diabetics and 43.7±3.5 ml/MM Hg in controls (P<0.014). The volume-pressure curves during deflation of the intragastric balloon were different from the curves during inflation, creating a hysteresis loop. The area between the inflation and deflation curves was 827 ml/mm Hg in diabetics and 627 ml/mm Hg in the controls (P=0.21). Gastric distension induced more upper gastrointestinal sensations in the patients than in the volunteers: nausea (P<0.002), bloating (P<0.003), upper abdominal pain (P<0.001). In conclusion: this study showed that the compliance of the proximal stomach is increased in diabetic patients with autonomic neuropathy and gastrointestinal symptoms. This abnormality, probably due to autonomic neuropathy, is associated with increased symptom generation during gastric distension.

Prognosis and life expectancy in chronic liver disease.

Abstract: The aim of the present was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population Among patients with cirrhosis, prognosis was dependent upon Child classification (P = 0001) Patients with alcoholic cirrhosis and fatty liver disease were younger (P = 001) and had a lower life expectancy than patients with other causes of chronic liver disease (P = 0004) Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population In patients with alpha 1-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P = 001) For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and alpha 1-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment In patients with hereditary liver disease, additional viral infection of alcohol abuse lead to a significant deterioration of life expectancy Patients with alcoholic chronic liver disease have the poorest prognosis

Nutrient-specific modulation of gastric mechanosensitivity in patients with functional dyspepsia.

Abstract: Intraduodenal lipid infusion induces symptoms and increases sensitivity to gastric distension in patients with functional dyspepsia. To test whether these effects are specific for lipid, we compared the effects of intraduodenal infusions of either lipid or glucose on symptoms and gastric sensory and motor responses to gastric distension. Eighteen dyspeptic patients and nine controls were studied. The stomach was distended with a flaccid bag during isocaloric infusions (1 kcal/ml) of saline and either 10% Intralipid (nine patients) or 26.7% glucose (nine patients) into the duodenum. Dyspeptic symptoms and sensory thresholds for epigastric fullness and discomfort were assessed. Gastric pressure profiles during distensions were similar during lipid and glucose infusions in patients and controls, but both were significantly lower than during saline infusion. Lower volumes were required to induce fullness and discomfort in the patients compared with the controls. In the controls, the threshold volumes required to induce fullness and discomfort were greater during infusion of lipid and glucose than during saline infusion, but in the patients, the threshold volumes were increased during glucose infusion but further reduced during lipid infusion. Moreover, in the patients, nausea was more common during lipid than glucose infusion and did not occur during saline. The controls did not experience any symptoms during any infusion. In conclusion, intraduodenal lipid but not glucose sensitizes the stomach to distension in patients with functional dyspepsia but not in controls.

Does massive obesity promote abnormal gastroesophageal reflux

Abstract: Fifty consecutive massively obese patients referred for gastroplasty operations were prospectively studied to determine the existence of gastroesophageal reflux disease by means of a standardized questionnaire, 24-hr ambulatory pH-metry, and endoscopy (27 females, mean age 48 years, range 38–57 years). These patients had a body mass index (BMI) of 42.5±5.2 kg/m2 and an actual weight of 125.5±17 kg. Heartburn and acid regurgitation was reported by 37% and 28%, respectively, mostly of a mild degree (22% and 20%). Dysphagia was reported by 2%, but none had odynophagia. No patient had any macroscopic esophagitis. The pH data were compared with those obtained in 29 age- and sex-matched, symptom-free, healthy controls (15 females, mean age 47.6 years, range 30–63 years). During ambulatory pH-metry, we recorded a predominance of daytime reflux (7.2±8.2% and a total acid exposure of 5.3±6.4%) in the obese patients, but neither the weight, BMI, nor the waist-hip ratio were significantly correlated with any of the reflux variables. The pH data obtained from these patients did not, however, differ significantly from those recorded in the control population, although a somewhat lower daytime acid reflux was found in the latter group. These results suggest that massive overweight is not associated with an increased prevalence of gastroesophageal reflux disease.

Pharmacological aspects of acid secretion

Abstract: The secretion of gastric acid is regulated both centrally and peripherally. The finding that H2-receptor antagonists are able to reduce or abolish acid secretion due to vagal, gastrinergic, and histaminergic stimulation shows that histamine plays a pivotal role in stimulation of the parietal cell. In the rat, the fundic histamine is released from the ECL cell, in response to gastrin, acetylcholine, or epinephrine, and histamine release is inhibited by somatostatin or by the H3-receptor ligand, R-alpha-methyl histamine. The parietal cell has a muscarinic, M3, receptor responsible for [Ca]i regulation. Blockade of muscarinic receptors by atropine can be as effective as H2-receptor blockade in controlling acid secretion. However, general effects on muscarinic receptors elsewhere produce significant side effects. The different receptor pathways converge to stimulate the gastric H+,K(+)-ATPase, the pump responsible for acid secretion by the stomach. This enzyme is an alpha,beta heterodimer, present in cytoplasmic membrane vesicles of the resting cell and in the canaliculus of the stimulated cell. It has been shown that acid secretion by the pump depends on provision of K+Cl- efflux pathway becoming associated with the pump. As secretion occurs only in the canaliculus, this K+Cl- pathway is activated only when the pump inserts into the canalicular membrane. Transport by the enzyme involves reciprocal conformational changes in the cytoplasmic and extracytoplasmic domain. These result in changes in sidedness and affinity for H3O+ and K+, enabling active H+ for K+ exchange. The acid pump inhibitors of the substituted benzimidazole class, such as omeprazole, are concentrated in the canaliculus of the secreting parietal cell and are activated there to form sulfenamides. The omeprazole sulfenamide, for example, reacts covalently with two cysteines in the extracytoplasmic loops between the fifth and sixth transmembrane and the seventh and eighth transmembrane segments of the alpha subunit of the H+,K(+)-ATPase, forming disulfide derivatives. This inhibits ATP hydrolysis and H+ transport, resulting in effective, long-lasting regulation of acid secretion. Therefore, this class of acid pump inhibitor is significantly more effective and faster acting than the H2 receptor antagonists. K+ competitive antagonists bind to the M1 and M2 transmembrane segments of the alpha subunit of the acid pump and also abolish ATPase activity. These drugs should also be able to reduce acid secretion more effectively than receptor antagonists and provide shorter acting but complete inhibition of acid secretion.

Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis

Abstract: This 12-month, double-blind, placebo-controlled study randomized 205 ulcerative colitis patients in remission to placebo or controlled-release mesalamine at 4 g/day for 12 months. Patients were stratified to either pancolitis or left-sided disease, based on previous diagnosis. Maintenance of remission was defined as a sigmoidoscopic index of <5, less than five stools per day, and the absence of rectal bleeding. A significantly greater number of patients maintained remission on mesalamine 4 g/day than on placebo at each of five study visits, following the first one-month visit (P<0.05). The estimated 12-month remission rates for the mesalamine group were 64% (38% for placebo,P=0.0004). Baseline subgroups (disease location, time since last flare of active disease, and previous response to oral/rectal steroids or sulfasalazine) did not influence remission rates. Treatment-related adverse events were rare. Controlled-release mesalamine is a safe and efficacious single agent for maintaining remission of ulcerative colitis.

Current theories of pathogenesis and treatment of nonocclusive mesenteric ischemia

Abstract: Nonocclusive mesenteric ischemia (NOMI) is a poorly understood condition marked by progressive intestinal ischemia leading to infarction, sepsis, and death in a high proportion of patients. The mortality rate for this intestinal disorder remains high, even when the diagnosis is made early in the disease course. This paper presents a comprehensive review of NOMI with a detailed discussion of its history, pathophysiology, diagnosis, and treatment.

IgA anti-endomysial antibodies on human umbilical cord tissue for celiac disease screening. Save both money and monkeys.

Abstract: Since celiac disease screening by traditional IgA anti-endomysial antibody test is limited by high costs of monkey esophagus commercial kits as well as by rising ethical problems related to the endangered species, the identification of an inexpensive and commonly available substrate for this antibody determination is urgently required. To achieve this goal, we compared the prevalence of IgA anti-endomysial antibodies detected on monkey esophagus with that on human umbilical cord. Fifty-seven (95%) of 60 untreated adult celiacs were positive for these antibodies on monkey esophagus as well as on human umbilical cord. IgA anti-endomysial antibodies, detected on both tissues, were negative in all 200 disease and healthy controls tested, displaying a 100% specificity for gluten-sensitive enteropathy. These data suggest that human umbilical cord can replace monkey esophagus for IgA anti-endomysial antibodies test. Human umbilical cord allows unlimited testing for celiac disease screening on wide series of high-risk subjects, permitting identification of greater numbers of asymptomatic celiac patients with a remarkable saving of money and bypassing the ethical problems related to killing monkeys.

Colonic lactate metabolism and D-lactic acidosis.

Abstract: d-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic producedd-lactate accumulates. An intestinal bypassed patient withd-lactic acidosis had higher fecald-lactate (122.4 mmol/liter) andl-lactate (90.1 mmol/liter) than described before in humans.d-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal<0.1 mmol/liter) and between 1.1 and 52.8 mmol/liter in urine (normal<0.7 mmol/liter) within a few hours, indicating that the human organism do metabolize and excreted-lactate. The patient withd-lactic acidosis had a 10-fold increasedDl-lactate production from glucose in fecal homogenates compared to 14 healthy controls and a patient with intestinal bypass, who did not haved-lactic acidosis. A 67% carbohydrate (starch)-enriched diet resulted in a minor elevation of fecal and plasma lactate, whereas 50 + 100+150 g of ingested lactose increasedd-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient withd-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasmad-lactate, but intestinal continuity was reestablished 26 months later becaused-lactic acidosis recurred (plasma 8.6 mmol/liter, urine 101.3 mmol/liter). Large amounts of lactulose (160 g/day) to 12 normal individuals increasedd-lactate to 13.6±3.5 mmol/liter in feces, but never increasedd-lactate in plasma or urine. Thein vitro fermentation of glucose in fecal homogenates increasedDl-lactate, which disappeared after complete metabolization of the glucose.l-Lactate was converted tod-lactate andvice versa, and both were degraded to the short-chain fatty acids acetate, propionate, and butyrate. An infrequent, but elevated ability of the colonic flora to produce lactate may be a prerequisite ford-lactic acidosis to occur and may explain why the syndrome is so seldom seen even in patients with intestinal bypass or short bowels. The suggestion thatd-lactate is not metabolized and hence accumulates is probably not valid.

Uptake and translocation of microparticles in small intestine. Morphology and quantification of particle distribution.

Abstract: The intestinal transit of large (micro-) particles to other sites of the body remains a controversial issue of relevance in various fields of study. In this report fluorescent polystyrene latex microparticles in the size range of 2 ώm were used as models for nonspecifically absorbed nonbiodegradable particulates. They were administered to young adult rats as a single oral dose of 1.65 × 109 particles; Peyer's patches and surrounding normal absorptive small intestinal tissue were collected at various time points. Quantification of solubilized tissue samples and fluorescence (epi- and confocal) qualitative and quantitative microscopy showed uptake of latex microparticles in all parts of the intestine sampled, but with the proximal segment the preferential site of absorption. The maximum uptake of particles occurred 0.5 hr after dosing in all three segments of the small intestine; there were progressively smaller numbers with distance from the pylorus and with time. Translocation of small numbers of particles to the mesenteric lymph nodes was also detected at 0.5 hr. Transmucosal passage of particles occurred primarily in the villous tissues adjacent to the Peyer's patch regions. These studies give confirmatory evidence for the uptake and translocation of microparticulates across the mucosal barrier and provide new information regarding site- and time-related effects on particle uptake and the involvement of the villous epithelium in particle translocation.