3-Aminobenzamide Prevents Concanavalin A-Induced Acute Hepatitis by an Anti-inflammatory and Anti-oxidative Mechanism.

BACKGROUND AND AIMS: Concanavalin A is known to activate T cells and to cause liver injury and hepatitis, mediated in part by secretion of TNFα from macrophages. Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors have been shown to prevent tissue damage in various animal models of inflammation. The objectives of this study were to evaluate the efficacy and mechanism of the PARP-1 inhibitor 3-aminobenzamide (3-AB) in preventing concanavalin A-induced liver damage. METHODS: We tested the in vivo effects of 3-AB on concanavalin A-treated mice, its effects on lipopolysaccharide (LPS)-stimulated macrophages in culture, and its ability to act as a scavenger in in vitro assays. RESULTS: 3-AB markedly reduced inflammation, oxidative stress, and liver tissue damage in concanavalin A-treated mice. In LPS-stimulated RAW264.7 macrophages, 3-AB inhibited NFκB transcriptional activity and subsequent expression of TNFα and iNOS and blocked NO production. In vitro, 3-AB acted as a hydrogen peroxide scavenger. The ROS scavenger N-acetylcysteine (NAC) and the ROS formation inhibitor diphenyleneiodonium (DPI) also inhibited TNFα expression in stimulated macrophages, but unlike 3-AB, NAC and DPI were unable to abolish NFκB activity. PARP-1 knockout failed to affect NFκB and TNFα suppression by 3-AB in stimulated macrophages. CONCLUSIONS: Our results suggest that 3-AB has a therapeutic effect on concanavalin A-induced liver injury by inhibiting expression of the key pro-inflammatory cytokine TNFα, via PARP-1-independent NFκB suppression and via an NFκB-independent anti-oxidative mechanism.

Anemia associated with acute infection in children: an animal model.

BACKGROUND: We constructed an animal model to examine the possibility that erythrophagocytosis may contribute to decreased hemoglobin (Hgb) levels in acute infection in mice. METHODS: BALB/c mice weighing 20 to 25 g were injected (intraperitoneally) with lipopolysaccharide (LPS) (Escherichia coli serotype) of some concentrations. Control mice were injected intraperitoneally with saline (0.5 mL). Two and 4 hours after LPS administration, mice were bled (0.25 mL) for complete blood count measures and tumor necrosis factor-α and interleukin-6 levels. The mice were then killed, and their spleen, liver, and bone marrow were examined microscopically for erythrophagocytosis. RESULTS: After LPS administration, mouse Hgb and hematocrit levels dropped significantly. At 4 hours after LPS injection, all Hgb and hematocrit concentrations were found to be significantly lower compared with that of controls (P = 0.002 and 0.001, respectively). Significantly increased concentrations of tumor necrosis factor-α and interleukin-6 were evident after LPS injection. Prominent hepatic erythrophagocytosis was observed in the LPS-injected mice compared with controls. A significant across-group difference was observed at 4 hours, driven by significantly higher values in group 500 mcg versus controls (P = 0.005) and 100 mcg (P = 0.025). A significant increase in erythrophagocytes was observed at 2 to 4 hours in the 500 mcg LPS group (P = 0.044). CONCLUSIONS: Erythrophagocytosis may play a role in anemia associated with acute infection in mice.

A rapid continuous-real-time 13C-urea breath test for the detection of Helicobacter pylori in patients after partial gastrectomy.

INTRODUCTION: Before the development of efficient medications for peptic ulcer disease many patients were treated surgically by partial gastrectomy. The pathogenetic role of Helicobacter pylori was also not known yet. Some of these patients may therefore still harbor H. pylori in their remnant stomach as a carcinogenic agent for gastric cancer. This could be even more relevant for patients who were operated for tumors in the stomach. The efficacy of the urea breath test (UBT) is not clear in this population. AIMS: To study the prevalence of H. pylori and to evaluate the sensitivity and specificity of the continuous UBT (BreathID) in postgastrectomized patients in Israel. In this system, the pH of the stomach is lowered by the addition of citric acid that may be beneficial in the smaller and more alkalic stomach. METHODS: We compared retrospectively the results of our continous UBT with a rapid urease test (RUT) and the histology in all our patients who underwent gastroscopy for any clinical indication, and had a history of partial gastrectomy during the years 2002 to 2010. Only patients in whom H. pylori was tested by all the 3 methods during the same day were included in the study. We identified 76 such patients older than 18 years and performed a statistical analysis of all possibly related clinical data. The 3 methods were compared with each other. RESULTS: H. pylori was positive in 14/76 (18.4%) patients when histology was considered as the gold standard method. The positive predictive value of the continuous UBT and the RUT was 0.64 and 0.35, respectively. The negative predictive value was high by both the methods, 0.92 and 0.95, respectively. Weight loss was correlated with positivity for H. pylori (P=0.032) and a longer gastric stump was marginally related to H. pylori (P=0.071). There was no difference for H. pylori positivity between patients with Billroth I or Billroth II operations. Prevalence of H. pylori was not lower in patients who had partial gastrectomy several years earlier. CONCLUSIONS: The prevalence of H. pylori is considerable even several years after partial gastrectomy. The BreathID is reliable to exclude H. pylori after partial gastrectomy. The positive predictive value of the UBT is not very high but better than the RUT. We suggest that all positive patients found by the breath test should be treated. Our results support the view that alternative noninvasive methods, such as the stool antigen test should be further studied and compared with the BreathID in larger populations.

Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: retrospective multicenter chart review study.

BACKGROUND: Carbon labeled urea breath tests usually entail a two point sampling with a 20 to 30-minute gap. Our aim was to evaluate the duration of time needed for diagnosing Helicobacter pylori by the BreathID® System. METHODS: This is a retrospective multicenter chart review study. Test location, date, delta over baseline, and duration of the entire test were recorded. Consecutively 13C urea breath tests results were extracted from the files over a nine year period. RESULTS: Of the 12,791 tests results, 35.1% were positively diagnosed and only 0.1% were inconclusive. A statistically significant difference in prevalence among the countries was found: Germany showing the lowest, 13.3%, and Israel the highest, 44.1%. Significant differences were found in time to diagnosis: a positive diagnosis had the shortest and an inconclusive result had the longest. Overall test duration averaged 15.1 minutes in Germany versus approximately 13 minutes in other countries. Diagnosis was achieved after approximately 9 minutes in Israel, Italy and Switzerland, but after 10 on average in the others. The mean delta over baseline value for a negative diagnosis was 1.03 ± 0.86, (range, 0.9 - 5), versus 20.2 ± 18.9, (range, 5.1 - 159.4) for a positive one. CONCLUSIONS: The BreathID® System used in diagnosing Helicobacter pylori can safely shorten test duration on average of 10-13 minutes without any loss of sensitivity or specificity and with no test lasting more than 21 minutes.

[Nodular regenerative hyperplasia as a complication of thiopurine treatment in a patient with inflammatory bowel disease].

Immunomodulator therapy with thiopurine analogues azathioprine or 6-mercaptopurine is commonly prescribed for the treatment of organ transplantation, inflammatory bowel disease, autoimmune diseases and malignancies. Hepatotoxicity due to thiopurine analogues usually presents as an increase in serum transaminase levels. Toxicity is usually not severe, and a dose reduction is effective in most patients. Nodular regenerative hyperplasia (NRH) is a very rare but potentially severe complication of thiopurine-containing therapy. NRH is often asymptomatic, neither biochemical nor molecular markers are indicative for NRH. The suspicion rises when there are clinical symptoms of portal hypertension or increases in transaminases levels orthrombocytopenia. Liver biopsy is essential for definitive diagnosis. This is a case report of a 40-year-old male patient with Crohn's disease who developed increased serum levels of liver enzymes and thrombocytopenia following the administration of thiopurine. Although treatment with thiopurine was discontinued, he has further progressed and presented with acute variceal bleeding due to portal hypertension. The diagnosis of nodular regenerative hyperplasia was proven by a liver biopsy. In conclusion, NRH is a very rare but potentially severe complication of thiopurine-containing immunosuppressive therapy for IBD.

Evaluation of the 13C-octanoate breath test as a surrogate marker of liver damage in animal models.

BACKGROUND: Octanoate (also known as sodium octanoate), a medium-chain fatty acid metabolized in the liver, is a potential substrate for non-invasive breath testing of hepatic mitochondrial beta-oxidation. METHODS: We evaluated the 13C-octanoate breath test (OBT) for assessing injury in acute hepatitis and two rat models of liver cirrhosis, first testing octanoate absorption (per os or intraperitoneally (i.p.)) in normal rats. We then induced acute hepatitis with thioacetamide (300 mg/kg/i.p., 24-h intervals). Liver injury end points were serum aminotransferase levels and 13C-OBT (24 and 48 h following initial injection). Thioacetamide (200 mg/kg/i.p., twice per week, 12 weeks) was used to induce liver cirrhosis. OBT and liver histological assessment were performed every 4 weeks. Bile duct ligation (BDL) was used to induce cholestatic liver injury. We completed breath tests with 13C-OBT and 13C-methacetin (MBID), liver biochemistry, and liver histology in BDL and sham-operated rats (baseline, 6, 14, 20 days post-BDL). RESULTS: Octanoate absorbs well by either route. Peak amplitudes and cumulative percentage dose recovered at 30 and 60 min (CPDR30/60), but not peak time, correlated with acute hepatitis. Fibrosis stage 3 at week 8 significantly correlated with each OBT parameter. Cholestatic liver injury (serum bilirubin, ALP, gamma-GT, liver histology) was associated with significant suppression of the maximal peak values and CPDR30/60, respectively (P<0.05),using MBID but not 13C-octanoate. CONCLUSIONS: OBT is sensitive for potentially evaluating liver function in rat models of acute hepatitis and thioacetamide-induced liver cirrhosis but not in cholestatic liver injury. The MBID test may be better for evaluation of cholestatic liver disease in this model.

Utility of a 13C-methacetin breath test in evaluating hepatic injury in rats.

BACKGROUND AND AIM: Methacetin is thought to be a good substrate for the evaluation of different cytochrome P450 enzymatic systems of liver microsomes because of its rapid metabolism and lack of toxicity in small doses. Recent studies indicate that a methacetin breath test may be a non-invasive alternative for the evaluation of liver function since it correlates well with the severity of liver damage. It may also discriminate between different stages of liver cirrhosis and correlates with the Child-Pugh score. The application of this test in experimental liver damage in animal models has not yet been examined. This study aimed to evaluate the efficacy of the (13)C-methacetin breath test in assessing the extent of hepatic injury in models of acute liver failure, liver cirrhosis, and fatty liver in rats. METHODS: Absorption of methacetin given per os or intraperitoneally in normal rats was evaluated. The association between liver mass and (13)C-methacetin breath test results was assessed in a 70% hepatectomy rat model. Fulminant hepatic failure was induced by three consecutive intraperitoneal injections of thioacetamide, 300 mg/kg, at 24 h intervals. For induction of liver cirrhosis, rats were given intraperitoneal injections of thioacetamide, 200 mg/kg, twice a week for 12 weeks. A methionine-choline deficient diet was used for the induction of fatty liver. Rats were analyzed for (13)C-methacetin by BreathID (MBID) using molecular correlation spectrometry. BreathID continuously sampled the animal's breath for 60 min and displayed the results on the BreathID screen in real-time. RESULTS: Methacetin was absorbed well irrespective of the administration method in normal rats. Liver mass was associated with peak amplitude, complete percent dose recovery (CPDR) at 30 and 60 min and MBID peak time. A high degree of association was also demonstrated with MBID results in acute hepatitis (peak amplitude, 19.6 +/- 3.4 vs 6.3 +/- 1.63.4; CPDR30, 6.0 +/- 3.3 vs 1.2 +/- 0.5; CPDR60, 13.3 +/- 4.5 vs 3.2 +/- 1.4; and peak time, 31.0 +/- 14.9 vs 46.9 +/- 10.8 min) and liver cirrhosis (peak amplitude, 24.4 +/- 2.3 vs 15.6 +/- 6.4; CPDR30, 7.9 +/- 1.2 vs 2.7 +/- 1.0; CPDR60, 17.8 +/- 2.6 vs 8.8 +/- 2.1; and peak time, 30.2 +/- 1.5 vs 59.6 +/- 14.5 min), but not with grade of liver steatosis. CONCLUSIONS: Methacetin is well absorbed and exclusively metabolized in the liver. MBID is a sensitive test and may be a useful tool for the evaluation of functional liver mass in animal models of acute liver failure and cirrhosis. However, MBID could not distinguish between fatty liver and normal liver in rats.

The cyclin-dependent kinase inhibitor, p27, has no correlation with the malignant potential of GIST.

BACKGROUND: Tumor size and mitotic activity are characteristically associated with the malignant potential and prognosis of gastrointestinal stromal tumors (GIST). However, since neither small tumor size nor low mitotic activity can rule out malignancy, additional factors that may predict malignant behavior have been suggested. AIM: To evaluate the correlation between the cyclin-dependent kinase inhibitor (CDI), p27kip1, expression and the malignant potential of GIST. METHODS: Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67 in surgical material obtained from 36 patients with GIST. p27kip1 staining intensity and the percentage of positive cells were investigated for association with the malignancy risk, pathological features, overall survival, and disease-free survival. Histologic grade was assigned by spindle vs. epithelioid cell histology, mucosal invasion, tumor cell necrosis or atypia and the number of mitoses. RESULTS: In the multivariate model, p27kip1 expression was not significantly associated with any of the variables examined except Kit protein-CD117 (r = 0.37, p = 0.03). Comparative evaluation of p27kip1 expression in GIST cells revealed higher levels of p27kip1 in patients who died compared to those who survived (2.04 +/- 0.54 vs. 1.3 +/- 0.99, p = 0.1). CONCLUSION: The CDI p27kip1 was not associated with malignancy of GISTs and did not serve as a predictor of survival.

p27kip1 expression is inversely related to the grade of gastric MALT lymphoma.

BACKGROUND: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. AIM: To evaluate p27kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. METHODS: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23-90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. RESULTS: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1+/-31.2 vs 17.3+/-20.6 (p=0.0001). The mean p27kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5+/-0.4 and 1.6+/-0.8, respectively (p=0.001). Comparative evaluation of p27kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27kip1, 0.36+/-0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64+/-0.53, advanced low-grade MALT lymphoma, 1.59+/-0.79, and localized low-grade MALT lymphoma, 1.59+/-0.84. In the multivariate model in which all p27kip1 variables were entered, the expression of p27kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07-0.31, p=0.0001. CONCLUSION: p27kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.

Endoscopic Occlusion of Tracheoesophageal Fistula in Ventilated Patients Using an Amplatzer Septal Occluder.

Acquired tracheoesophageal fistula (TEF) is a challenging, life threatening condition. It most commonly appears in critically ill patients requiring prolonged mechanical ventilation, who cannot withstand open neck or chest surgery. An endoscopic technique could be better tolerated by these patients. We present our experience using a cardiac Amplatzer ASD septal occluder for an endoscopic TEF repair in ventilation-dependent patients. Two high risk patients underwent the procedure under general anesthesia and close respiratory monitoring. In one patient the device was inserted through the trachea and in the other through the esophagus. In both cases fistula closure was achieved for different periods of time allowing the patients a temporary relief of symptoms. The procedure was well tolerated by the patients, and no significant adverse effect documented. The technique was successful as a temporary solution for unstable patients with TEFs and should be considered as a treatment modality for similar patients.

Fecal incontinence secondary to CAPD.

A 74-year-old patient who has developed fecal incontinence following continuous ambulatory peritoneal dialysis (CAPD) is presented. Incontinence was caused by elevated intra-abdominal pressure during peritoneal dialysis, which correlated with the volume of dialysate and position of the patient. The lowest pressure was found in the recumbent position. A change of dialysis schedule to continuous cycler peritoneal dialysis (CCPD) with "dry day" resulted in a disappearance of the symptoms.

The effect of acarbose on the colonic transit time of elderly long-term care patients with type 2 diabetes mellitus.

BACKGROUND: Constipation is common in elderly patients with diabetes mellitus (DM); its prevalence is estimated as up to 60% among patients with diabetic neuropathy. Acarbose, an alpha-glucosidase inhibitor, has a beneficial role in controlling DM, although one of its side effects is diarrhea. This study evaluates the efficacy of acarbose in improving constipation using transit time (TT) studies in elderly long-term care (LTC) patients. METHODS: Twenty-eight patients with type 2 DM and constipation were recruited for the study. TT was measured by radiopaque markers and was calculated separately for the four segments of the colon (ascending, transverse, descending, and rectosigmoid) and for the total colonic transit time (CTT). Segmental TT and CTT were evaluated in each patient before and after 1 week, and again after 4 weeks of treatment with acarbose. RESULTS: The mean baseline CTT measured in patients was 202 plus minus 136 hours. After 1 and 4 weeks of acarbose treatment, the baseline CTT significantly decreased to 149 plus minus 107 hours and 161 plus minus 97 hours, respectively (p <.002). For each segment studied, the TT was shortened, but it reached significance for the ascending and transverse colon only (p <.02 and p <.03, respectively). The effect of diet composition was examined. The amount of fiber consumed correlated with shortened CTT, while fat tended to be in negative correlation with TT. CONCLUSIONS: Acarbose therapy reduced the extremely prolonged CTT in LTC diabetic persons with constipation. The drug could be useful in relieving constipation in these patients, in addition to its beneficial effect in the control of diabetes.

Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis.

BACKGROUND:: Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage. AIM:: To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis. METHODS:: Steatohepatitis was induced in rats by placing them on a methionine-choline deficient diet for 1 month. Thioacetamide was administered by three consecutive intraperitoneal injections (300mg/kg) at 24h intervals. RESULTS:: Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necroinflammation and the survival rate after 48h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when steatohepatitis regressed after return to normal diet for 1 month (P < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between livers with steatohepatitis and steatohepatitis after regression, suggesting that the enhanced hepatotoxicity after regression of steatohepatitis could not be attributed to increased cytochrome P4502E1. CONCLUSIONS:: In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with steatohepatitis after 1 month regression.

Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders.

BACKGROUND: Epidemiologic studies in different parts of the world have revealed controversial results on the association between hepatitis C virus infection and non-Hodgkin's lymphoma. This discrepancy suggests that HCV lymphotropism or its effect on host lymphocytes may be influenced by regional and racial factors, as well as by genomic variations. OBJECTIVE: To determine the prevalence of HCV infection in patients with lymphoproliferative disorders diagnosed and treated in our institute in Israel. METHODS: A total of 212 consecutive patients (95 males and 117 females) treated in our hematology outpatient clinic between August 1997 and September 1999 was screened for anti-HCV antibodies and hepatitis B surface antigen. HCV infection was confirmed by the presence of HCV RNA in the serum. The prevalence of HCV in patients with lymphoproliferative disorders was compared to that in a control group of patients with myeloproliferative disorders and myelodysplastic syndromes. RESULTS: HCV infection was more prevalent in the group of LPD patients than in the control group, but this finding was not statistically significant. The prevalence of HCV among LPD patients was 7.8%, while that in the group with myeloproliferative and myelodysplastic disorders was 1.19% and in the general population 0.64%. Among the different classes of LPD, a significant association with HCV infection was established only in patients with diffuse large B cell lymphoma. Furthermore, HCV infection was significantly more prevalent than HBV infection in the LPD group, but not in the myeloproliferative and myelodysplastic disorders group. CONCLUSIONS: Our finding of a significant association between HCV infection and diffuse large B cell lymphoma leads us to suggest that anti-HCV antibodies be performed routinely in such subjects.

Early satiety is the only patient-reported symptom associated with delayed gastric emptying, as assessed by breath-test.

BACKGROUND/AIMS: To evaluate associations between delayed gastric emptying (GE) assessed by the octanoic acid breath test and upper gastrointestinal (GI) symptoms. METHODS: A historical, prospective study included 111 consecutive symptomatic adults referred for a GE breath test because of upper abdominal symptoms suggestive of delayed GE. Exclusion criteria included underlying organic disease associated with delayed GE. Patients completed a symptom questionnaire and underwent a GE octanoic breath test. Patients with delayed GE were compared with those with normal results, for upper GI symptoms. RESULTS: Early satiety was the only symptom significantly associated with delayed GE. It was observed in 52% of subjects with delayed GE compared to 33% patients with no evidence of delayed GE (P = 0.005). This association was seen for all degrees of severity of delayed GE. Patients with early satiety had a t(1/2) of 153.9 ± 84.6 minutes compared to 110.9 ± 47.6 minutes in subjects without it (P = 0.002). In a logistic regression model, early satiety was significantly associated with delayed GE (OR, 2.29; 95% CI, 1.01-5.18; P = 0.048). CONCLUSIONS: Early satiety is the only patient-reported GI symptom associated with delayed GE. The utility of GE tests as a clinical diagnostic tool in the work-up of dyspeptic symptoms may be overrated.

Modified endoscopic swallowing test for improved diagnosis and prevention of aspiration.

Laryngopharyngeal sensation is important in the normal process of swallowing, it is often impaired after neurological events and it has been common practice in such an occurrence to order non-oral tube feeding to prevent aspiration. This study assesses a novel approach to the evaluation of the laryngopharyngeal sensation that allows for improved triage of aspiration risk and more lenience towards oral feeding. This is a case series with follow-up period ranging from 6 to 24 months. Forty patients with neurological deficiencies were tested by a modified laryngopharyngeal sensation study that included evaluation of both supra and infra-glottis. All patients had impaired supra glottic sensation but had good infra glottic sensation that enabled cough protection. All had received oral feeding. Main outcome measure is incident aspiration pneumonia. Twenty-two patients maintained oral feeding without any evidence of aspiration. Eighteen patients had some aspirations associated with cough, and were maintained on modified oral feeding. Out of these 18 patients, four patients (10% of the entire group) developed aspiration pneumonia. The presented procedure identified patients with impaired supraglottic sensation but preserved good infra glottic sensation. This observation enables safe oral feeding in most patients and therefore offers a better quality of life for these individuals.

Eradication of Helicobacter pylori can be accurately confirmed 14 days after termination of triple therapy using a high-dose citric acid-based 13C urea breath test.

BACKGROUND: Confirmation of Helicobacter pylori eradication by urea breath test (UBT) is currently performed 4-6 weeks after completion of therapy because of unacceptable false-negative results in UBTs performed earlier. Use of a high-dose citric acid test meal appears to enable accurate detection of H. pylori even during short term therapy with proton pump inhibitors. AIM: To evaluate if use of a high dose citric acid (4.0 g) test meal can decrease the interval required for confirmation of eradication after triple therapy. METHODS: 233 patients positive for H. pylori were randomized to undergo UBT at 7 days or 14 days after triple therapy, and again at 6 weeks. The latter test was considered the gold standard test. RESULTS: The UBT performed 6 weeks after the end of treatment found that 79.9% were cured. The same test 7 days after therapy found false-negative detection of H. pylori in 7.3% patients compared to 3.2% patients examined after 14 days. The sensitivity, specificity, positive and negative predictive values and accuracy for evaluation on day 14 were 80, 100, 100, 96.3 and 96.7%, respectively. CONCLUSIONS: High-dose citric acid-based UBT is a valid test for the assessment of H. pylori status 14 days after triple therapy. This may obviate the delay in instituting second-line eradication therapy, or further evaluation of the symptomatic patient unresponsive to therapy despite eradication.

Chronic cholestasis associated with Turner's syndrome: 12 years of clinical and histopathological follow-up.

Clinically significant liver disease is probably a rare condition in Turner's syndrome and only a few cases of severe liver disease have been described. The natural history of patients with Turner's syndrome and elevated cholestatic liver enzymes is unclear. We report a case with a long history of intrahepatic cholestasis and without clinical or histopathological progression in 12 years of follow-up. Like some other reports our case suggests, also histologically, that the liver disease in these patients runs a benign course.

Thioacetamide-induced hepatic damage in a rat nutritional model of steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis is most often attributed to the effects of obesity, hyperlipidemia, diabetes mellitus and drugs. It is still unknown whether livers with steatohepatitis are more vulnerable to toxic damage. AIM: To determine the effect of the hepatotoxicant thioacetamide in a rat nutritional model of hepatic steatohepatitis. METHODS: Fatty liver was induced in rats by placing them on a methionine-choline deficient diet for one month. Thioacetamide was administered by 3 consecutive intraperitoneal injections (300 mg/kg) at 24 h intervals. RESULTS: Following treatment with thioacetamide, the elevated serum levels of liver enzymes and blood ammonia, liver necrotic inflammation and the survival rate after 48 h were not different between rats with normal or fatty liver. However, those parameters were significantly worse when fatty liver regressed after return to normal diet for one month (p < 0.01). Western blot analysis of hepatic extracts revealed no difference in cytochrome P4502E1 levels between fatty livers and fatty livers after regression, suggesting that the enhanced hepatotoxicity after regression of fatty liver could not be attributed to increased cytochrome P4502E1. CONCLUSIONS: In a nutritional model of steatohepatitis, rats with fatty liver were not more vulnerable than normal rats to liver damage induced by thioacetamide. However, liver damage was significantly more severe in rats with fatty livers after one month regression of steatosis.

Effect of heparin on tissue binding activity of fibroblast growth factor and heparin-binding epidermal growth factor in experimental colitis in rats.

There have been several reports implying a benefit for heparin therapy in patients with refractory ulcerative colitis. Although this effect has been attributed to the anti-inflammatory properties of heparin, other mechanisms have not been excluded. Heparin is a potent modulator of receptor binding of growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, and heparin-binding epidermal growth factor (HB-EGF), that play a role in wound repair. We examined the effect of heparin on the functional levels of FGF and HB-EGF in a model of experimental colitis. Fifty-six Wistar rats were divided into four groups: group 1 was the control group, group 2 received s.c. heparin 50 units/kg/d, group 3 underwent induction of 3% iodoacetamide colitis, and group 4 underwent induction of colitis and heparin treatment. Rats were killed and evaluated for severity of colitis by macroscopic and microscopic colitis scores, area of inflammation, and myeloperoxidase levels. FGF and HB-EGF levels were functionally assessed in colonic tissue in each group. Heparin therapy resulted in significant improvement in macroscopic and microscopic features of colitis (p < 0.05), accompanied by a partial reduction in myeloperoxidase levels. FGF receptor binding activity was identical in groups 1 and 2 but increased more than 3-fold after colitis induction in group 3 (p < 0.05). Treatment with heparin caused a significant decrease in FGF concentration. Levels of HB-EGF binding activity were similar in groups 1 and 2 and decreased in group 3 (p < 0.01). Heparin caused a significant increase in HB-EGF content in group 4 (p < 0.05). Levels of growth factors are altered differently in experimental colitis. Colonic FGF binding activity increases with colitis, whereas HB-EGF binding decreases with colitis. These trends were reversed by heparin, concomitant with a clinical and pathologic improvement in colitis. We suggest that one mechanism of heparin-mediated improvement in colitis may involve tissue healing associated with changes in functional levels of colonic growth factors.