An Israeli national survey on ischemic colitis induced by pre-colonoscopy bowel preparation (R1).

Background and study aims: Ischemic colitis (IC) may occur as a complication of colonoscopy. The aim of this study was to characterize patients with IC that occurred after exposure to bowel preparation laxatives, prior to an elective colonoscopy. Patients and methods: A survey among Israeli gastroenterologists. Information was collected regarding individual cases. Results: Eight patients, who developed IC after bisacodyl ingestion that was taken as part of pre-colonoscopy bowel preparation protocol, were reported. In all patients, severe abdominal pain and/or hematochezia started shortly after the ingestion of the first dose of bisacodyl. IC was found in 7 patients during the planned colonoscopy and in 1 patient using computerized tomography. All patients received supportive treatment and recovered. Conclusions: IC induced by bisacodyl is a rare phenomenon. Regardless of being rare, we would advise withholding bisacodyl bowel preparation in elderly subjects with risk factors for IC that are scheduled for a colonoscopy.

Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation.

BACKGROUND AND PURPOSE: We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. EXPERIMENTAL APPROACH: Cannabidiol (5 mg x kg(-1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(-1)), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin. KEY RESULTS: Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis factor-alpha receptor 1 and the BDNF genes, which increased and decreased, respectively, following BDL. It did not affect reduced 5-HT(1A) expression in BDL mice. All the effects of cannabidiol, except for that on BDNF expression, were blocked by WAY-100635, indicating 5-HT(1A) receptor involvement in cannabidiol's effects. Cannabidiol did not affect the impaired liver function in BDL. CONCLUSIONS AND IMPLICATIONS: The behavioural outcomes of BDL result from both 5-HT(1A) receptor down-regulation and neuroinflammation. Cannabidiol reverses these effects through a combination of anti-inflammatory activity and activation of this receptor, leading to improvement of the neurological deficits without affecting 5-HT(1A) receptor expression or liver function. BDNF up-regulation by cannabidiol does not seem to account for the cognitive improvement.

The clinical spectrum of cytomegalovirus colitis in adults.

BACKGROUND: Colonic cytomegalovirus reactivation rarely occurs in adults without inflammatory bowel disease or a known immunosuppressive state. AIM: To describe our experience with such patients. METHODS: All consecutive admissions of patients with possible cytomegalovirus colitis, between 1995 and 2006, were reviewed retrospectively. RESULTS: Nineteen patients were studied. Most of the patients were elderly with multiple co-morbidities. Three main forms of disease presentation were recognized: acute diarrhoea, chronic diarrhoea and lower gastrointestinal bleeding. Colonic mucosal intranuclear inclusion bodies were found in 12 patients. Thirteen patients had cytomegalovirus viraemia (either by polymerase chain reaction and/or by white blood cell-cytomegalovirus antigenaemia test). Ganciclovir therapy was given to only eight patients; only five of these patients survived. The other subgroup of 11 patients received only supportive therapy. Most of the patients from this subgroup had a prolonged and complicated hospital course; only nine patients survived. Follow-up colonoscopies were performed only in five patients (out of the 14 patients who survived). In four of these patients, chronic mucosal inflammatory changes were noted. CONCLUSIONS: Cytomegalovirus colitis occurs rarely in adult individuals. The disease may have various and multiple acute and/or chronic clinical manifestations. Clinical awareness of this condition is needed.

Lamivudine treatment for acute severe hepatitis B: a pilot study.

BACKGROUND: Experience with lamivudine treatment of immunocompetent patients with acute hepatitis B is limited. AIM OF STUDY: To evaluate the safety and efficacy of lamivudine for the treatment of acute severe hepatitis B virus (HBV) infection in immunocompetent adults. PATIENTS AND METHODS: Fifteen patients (10 men, 5 women, mean age 34.3+/-7.3 years) with severe acute HBV infection were treated with lamivudine 100 mg daily for 3-6 months, starting 3-12 weeks after onset of infection. Prior to treatment, 5 patients had grade 1-4 encephalopathy; all patients had severe coagulopathy (mean INR was 4.5+/-6.4), and all patients had evidence of severe hepatocyte lysis (mean alanine aminotransferase 3738+/-1659 U/L, and mean total serum bilirubin 18+/-6.8 mg/dl). All patients had evidence of highly replicative HBV (mean HBV DNA 13.5 x 10(6)+/-11 x 10(6) copies/ml). RESULTS: Thirteen patients (86.6%) responded to treatment. Encephalopathy disappeared within 3 days of treatment and coagulopathy improved within 1 week. Serum HBV DNA was undetectable (by polymerase chain reaction) within 4 weeks, and serum liver enzyme levels normalized within 8 weeks. Two patients in whom lamivudine therapy was delayed developed fulminant hepatitis and underwent urgent liver transplantation. (One died of vascular complications 1 month later). The 11 patients who were serum HBeAg-positive before treatment seroconverted, and HBeAb developed within 12 weeks in 9 of them; HBsAg was undetectable in all 11 tested patients, and protective titer of HBsAb developed within 12-16 weeks in 9 of them. Therapy was well tolerated in all cases. CONCLUSIONS: These data indicate that lamivudine induces a prompt clinical, biochemical, serological and virological response in immunocompetent patients with de novo HBV infection. Lamivudine may prevent the progression of severe acute disease to fulminant or chronic hepatitis and should be considered for use in selected patients. A large randomized controlled, double-blind prospective study is needed.

Longitudinal prostaglandin E(2) generation in various organs during evolution of experimental portal hypertension.

It has been suggested that the arteriolar vasodilatation and hyperdynamic circulation observed in rats with partial portal vein ligation (PPVL) is caused by increased splanchnic and systemic delivery of vasodilator substances. The aims of our study were to determine organ-specific generation of prostaglandin E(2) (PGE(2)) in rats with PPVL during the evolution of portal hypertension. Rats with PPVL and sham-operated (S) rats were studied in the first, third, fourth and 14th postoperative days. They were anesthetized and splenic pulp pressure and blood pressure were measured. Spleen, colon and lungs were removed and the splenic, pulmonary and mucosal colonic PGE(2) were determined. All PPVL rats developed sequential hemodynamic changes compatible with evolving portal hypertension. Splenic pulp pressure was higher in PPVL rats compared with S rats during all days of the study. Within the group of PPVL the splenic pulp pressure was higher in the first postoperative day and decreased in the ensuing days. No changes in splenic and colonic PGE(2) generation were noted during the study period. Pulmonary PGE(2) generation increased significantly in the first postoperative day in PPVL rats compared with S rats. However, similar increase was observed on the third postoperative day in S rats. PGE(2) probably has no role in splanchnic hemodynamic changes during evolution of portal hypertension. Pulmonary PGE(2) generation may increase as a response to increased portal pressure, or to abdominal surgery.

[Does incidence of hepatitis A increase during shmitah (the Sabbatical year)?].

In Israel the biblical injunction of the sabbatical year (shmitah) prevails, whereby all Jewish-owned land should lie fallow during every seventh year. Consequently, it is customary for members of the orthodox Jewish community to eat only produce grown by non-Jews (Arabs). Many Arab farmers use sewage water for irrigation and since such water could be infected with hepatitis A virus (HAV), there is concern about the possibility of HAV epidemics during the sabbatical year. We therefore we examined the data of the Israeli Center for Disease Control (ICDC). We found no obvious increase in incidence of viral hepatitis during, nor in the year immediately after, all sabbatical years since 1951. However, the data was not comprehensive as it included only partial information on morbidity from HAV in our Jewish inhabitants. Also, there was no data specific for the orthodox Jewish community, which is especially at risk for HAV from sewage-irrigated vegetables. Irrespective of shmitah, there should be constant effort to prevent HAV infection in Israel.

Intrafamilial transmission of hepatitis C virus: a systematic review.

To examine the risk of hepatitis C virus (HCV) transmission between patients infected with HCV and their household members (siblings, offspring and parents), as well as their stable heterosexual partners, a systematic search of the MEDLINE database was undertaken for all relevant articles published up to June 1997. English language publications or those supplemented with an English abstract that reported studies concerning hepatitis C, and household, intrafamilial, sexual and intraspousal transmission of HCV, were reviewed. Data from uncontrolled and controlled studies were collected and analysed separately. Studies reporting the exclusive use of first-generation anti-HCV antibodies without supplemental tests were excluded. Pre- or postnatal mother-to-child transmission of HCV and homosexual and heterosexual transmission of HCV among non-permanent couples were not included. Unweighted data from individual studies were pooled for each category of family member. Data were also analysed separately for Japanese and non-Japanese studies because there is evidence that intrafamilial transmission may differ, based on endemicity of the viral infection. Comparisons were drawn only from controlled studies that reported the prevalence of HCV in family members of both HCV-positive and HCV-negative controls. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated for each family category. In uncontrolled studies, the pooled prevalence of anti-HCV among 4250 stable sexual contacts of patients with HCV-related chronic liver disease (CLD) was 13.48%, while the pooled prevalence of anti-HCV among 580 stable sexual contacts of patients who contracted HCV as a result of multiple transfusions was 2.41%. In controlled studies, the pooled prevalence of anti-HCV among 175 siblings and household contacts of patients with CLD was 4.0% compared with 0% among 109 contacts of anti-HCV-negative controls (OR 9.75, 95% CI 0.91 ad infinitum). The pooled prevalence of anti-HCV among offspring of Japanese HCV-infected CLD patients was 17% compared with 10.4% among offspring of HCV-negative Japanese controls (OR 1.77, 95% CI 1.21-2. 58, P=0.002). The pooled prevalence of anti-HCV among spouses of non-Japanese HCV-infected CLD patients was 15.2% compared with 0.9% in the spouses of non-Japanese HCV-negative controls (OR 20.57, 95% CI 6.05-84.08, P=0.0001). The prevalence of anti-HCV among non-Japanese offspring and Japanese spouses of HCV-infected patients was not increased compared with controls. HCV genotype homology and mutant analysis studies in pairs of HCV-infected patients and their HCV-infected contacts showed that concordant genotype homology was found in 66% of non-sexual contacts and in 74% of sexual contacts. Sequence homology of greater than 92% was found in 19 out of 35 pairs. Hence, evidence exists that familial, non-sexual and sexual transmission of HCV does occur. In Japanese patients, transmission probably occurs in younger family members while, in non-Japanese patients, transmission probably occurs at an older age, after contact with an HCV-infected spouse.

Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease.

OBJECTIVE: Reduced bone mineral density (BMD) is common in patients with inflammatory bowel disease (IBD), but the factors associated with its longitudinal rate of change have not been established. We prospectively assessed the rate of change in BMD, and its association with biochemical markers of bone turnover. METHODS: Twenty-two patients with Crohn's disease and 14 ulcerative colitis patients age 37.1 +/- 11.6 yr were followed for 2 yr. Lumbar spine (L2-L4) and femoral neck BMD were measured by dual x-ray absorptiometry at baseline and 24 months. Bone-specific alkaline phosphatase, osteocalcin, urinary N-telopeptide crosslinked type 1 collagen (NTx), parathyroid hormone, and 25-hydroxyvitamin-D were determined at baseline. RESULTS: At baseline, 59% of Crohn's patients and 43% of ulcerative colitis patients were osteoporotic, with spine or femoral neck BMD T-score < -2.5. Spine BMD, and spine and femoral neck T-scores were lower and disease duration was longer in nine patients with ileal resection compared with nonoperated patients (0.84 +/- 0.15 g/cm2 vs 0.96 +/- 0.11 g/cm2, -3.0 +/- 1.5 vs -1.7 +/- 1.3, -3.2 +/- 1.5 vs -2.2 +/- 1.0, respectively; all p < 0.05). At 24 months, 13/36 (36%) and 14/36 (39%) patients experienced spinal and femoral neck bone loss, respectively, with mean annual percent BMD changes of -2.0% and -1.5%, respectively. NTx, a bone resorption marker, inversely correlated with spinal BMD rate of change (r = -0.4, p < 0.05). Using quartiles analysis, patients with the highest NTx (Q4) experienced the greatest decrease in spine BMD compared with patients with the lowest NTx (Q1). CONCLUSIONS: Spine and femoral neck bone loss continues over time in more than one-third of IBD patients. Increased NTx level predicts spinal bone loss in IBD patients.

Lymphocytic colitis: a clue to an infectious trigger.

We present a 19-year-old patient who was admitted for evaluation of prolonged watery diarrhea. Previous study showed one stool culture positive for Campylobacter jejuni, which was treated with appropriate antibiotics with no response. She underwent colonoscopy with multiple biopsies, which led to a diagnosis of lymphocytic colitis. We believe that the patient's disease was due to the infectious process, which triggered an autoimmune response and caused the lymphocytic colitis.

Unusual gallbladder findings in two brothers with metachromatic leukodystrophy.

Characteristic biliary tree abnormalities in metachromatic leukodystrophy (MLD) include gallbladder polyposis and haemobilia. We report two brothers with MLD, who presented with uncommon biliary complications. One presented with gastric outlet obstruction secondary to gallbladder enlargement, which was treated by percutaneous aspiration. He later developed gallbladder carcinoma with liver metastases. His brother demonstrated US findings consistent with gallstones.

Femoral neck osteopenia in patients with inflammatory bowel disease.

OBJECTIVE: The mechanism of bone loss in patients with inflammatory bowel disease (IBD) is not completely understood. The aim of this study was to assess indices of bone turnover and bone mineral density (BMD) in the lumbar spine and femoral neck in IBD patients. METHODS: Sixty-three patients with Crohn's disease and 41 with ulcerative colitis were studied. Serum bone-specific alkaline phosphatase (B-ALP), osteocalcin, parathyroid hormone (PTH), 25 hydroxyvitamin D, interleukin-6 (IL-6), and urinary N-telopeptide cross linked type 1 collagen (NTX) were determined. BMD of the lumbar spine and femoral neck was determined by dual x-ray absorptiometry in 59 patients. RESULTS: In the femoral neck 42% of the patients had osteopenia (-2.5 SD < BMD T score < -1 SD) and another 41% had osteoporosis (BMD T score < -2.5). In the spine 34% of the patients had osteopenia and additional 42% had osteoporosis. BMD T scores were lower in the femoral neck compared to the spine. Reduced BMD was unrelated to gender, disease type, lifetime corticosteroid dose, but inversely correlated with disease duration (r = -0.36, p < 0.05). Serum IL-6 was higher in IBD patients compared to controls. A reduced level of osteocalcin, a marker of bone formation, was present in 7% of patients and an increase in NTX, a marker of bone resorption, in 25% of them. Osteoporotic IBD patients (spine or hip BMD T score < -2.5) had increased serum IL-6, osteocalcin and PTH level compared to nonosteoporotic patients. CONCLUSIONS: There is a high prevalence of reduced BMD at the spine and femoral neck in IBD patients, which is more severe in the hip. Bone turnover in osteoporotic IBD patients is associated with an increase in osteocalcin, PTH and IL-6. IL-6 may play a role in the pathogenesis of bone loss in IBD.

Ischemic hepatitis: clinical and laboratory observations of 34 patients.

Ischemic hepatitis, a relatively infrequent disorder occurring in 0.16% to 0.50% of patients admitted to medical intensive care units, often follows episodes of hypotension or acute heart failure. Investigating the clinical characteristics of patients with ischemic hepatitis may add to our understanding of the pathogenesis and significance of this syndrome. We therefore conducted a retrospective analysis of 34 patients to examine the possible contribution of the various baseline characteristics to the severity of the hepatic damage. In all patients liver disease was unexpected and in some, liver dysfunction dominated the clinical picture. All patients had high serum glutamic pyruvic transaminase (SGPT) and lactic dehydrogenase (LDH) levels (mean +/- SE, 2073 +/- 255 international units and 6085 +/- 748 international units, respectively). The mean SGPT/LDH ratio was 0.34. Most patients had coagulopathy with a prolonged prothrombin time (mean +/- SE, 5.86 +/- 1.37 international normalized ratio [INR]). The most common diagnosis on admission was respiratory distress secondary to various causes. Before the development of the hepatic dysfunction, respiratory failure and hypoxemia were observed in 68% of the patients, whereas hypotension was observed in only 38%. More than 90% of the patients had three or more associated comorbid conditions. The most frequent of these were left heart failure (88.2%), right heart failure (67.6%), chronic obstructive lung disease (58.8%), and chronic renal failure (55.9%). During the acute episode, more than 90% of the patients had transient deterioration of their renal functions. Hypoglycemia was noted in 11 patients (32.4%), and the glucose level was inversely correlated with the SGPT level (r = -0.43, p = 0.01). Stepwise multiple regression analysis showed that left heart failure, systolic blood pressure lower than 90 mm Hg, and female gender, together, accounted for 34% of the variance of the peak SGPT levels (p = 0.002). Fourteen (41.2%) patients died during the 3-month follow-up period, but none from the hepatic injury. None of the clinical or laboratory parameters measured predicted mortality. Clearly, ischemic hepatitis is associated with a high risk of death. The characteristic patients are those with multiple underlying systemic diseases and conditions, especially those with left heart failure. Liver function test results and levels of liver enzymes should be monitored in these patients, particularly when they are admitted for respiratory deterioration and episodes of hypotension.

Direct determination of colonic nitric oxide level--a sensitive marker of disease activity in ulcerative colitis.

OBJECTIVE: In active ulcerative colitis, colonic nitric oxide (NO) generation is enhanced and probably has an important role in its pathogenesis. We tested the reliability of an NO electrode in monitoring colonic NO levels in ulcerative colitis patients and control subjects and its possible usage as a marker of disease activity. METHODS: Colonic NO level was determined by the NO detection system model NO-501 (InterMedical, Nagoya, Japan). The working electrode was inserted into a 7-mm diameter polyvinyl tube and introduced at a distance 6 cm from the anus. In each subject sigmoidoscopy was performed and mucosal biopsies were obtained. NO synthase (NOS) activity was determined by monitoring the conversion of 3H-arginine to citrulline. RESULTS: Colonic NO level is significantly increased in patients with active ulcerative or Crohn's colitis--more than 2-fold higher than in control subjects. There was good correlation between colonic NO level and NOS activity and the clinical and endoscopic indices of disease activity. CONCLUSION: Direct determination of colonic NO level is convenient, and reliable, and may help to monitor disease activity in ulcerative colitis.

The contraceptive choice for a Wilson's disease patient with chronic liver disease.

Preserved fertility status is frequently encountered in patients with Wilson's disease, and contraceptive counseling may, therefore, be a relevant issue. Yet, several contraceptive methods can adversely influence the hepatic function, and the efficacy of others may be affected by the liver disease. We describe a patient with Wilson's disease manifested by cirrhosis, portal hypertension, and bleeding esophageal varices who underwent termination of pregnancy at 9 weeks' gestation. Following the procedure, contraceptive advice was sought in order to postpone conception until portal hypertension was controlled and hepatic function improved. Intramuscular depot medroxyprogesterone acetate was administered and tolerated well by the patient. A detailed discussion of the contraceptive options for patients with chronic liver disease, in general, and Wilson's disease, in particular, follows the case report.

PIP: Although the fertility status of women with Wilson's disease may be preserved, contraceptive method choice is complicated by the tendency for some methods to have an adverse effect on hepatic function and, conversely, for liver disease to compromise the efficacy of some contraceptives. This paper presents the case of a 28-year-old woman diagnosed with Wilson's disease at 13 years of age. She presented to an Israeli hospital at 9 weeks' gestational age with bleeding esophageal varices, cirrhosis, and portal hypertension. Although the patient had been oligomenorrheic, with menses every 2-3 months, she had experienced 3 spontaneous first-trimester abortions. Due to the urgent need for a portal decompression shunt procedure and the risk of further bleeding, the patient opted to terminate the current pregnancy. To prevent conception until the patient's liver condition stabilized, she was injected with Depo-Provera and penicillamine treatment was resumed. Although IUDs and estrogen-containing oral contraceptives are relatively contraindicated in women with liver dysfunction, spermicide and barrier contraceptives are highly recommended and progesterone-only preparations can be safely prescribed.