Comparison of central and intraesophageal factors between gastroesophageal reflux disease (GERD) patients and those with GERD-related noncardiac chest pain.

Gastroesophageal reflux disease (GERD) causes a wide range of symptoms. Some patients present with typical symptoms such as heartburn and regurgitation and others with atypical symptoms such as chest pain. The mechanism responsible for the varying clinical presentation of GERD is still not fully elucidated. The aim of this study was to prospectively evaluate differences in central and local intraesophageal factors between patients with typical GERD symptoms and those with noncardiac chest pain (NCCP). Patients presenting with typical and atypical symptoms suspicious of GERD underwent upper endoscopy and 24-hour pH monitoring with four sensors, each positioned at a different esophageal level. All patients completed GERD symptom, Hospital Anxiety and Depression Scale, and Symptom Stress Rating questionnaires. From January 2006 to December 2009, 50 patients were recruited, 29 with typical symptoms, and 21 with NCCP. Patients with proven GERD and NCCP had higher proximal extension of acid during reflux episodes than patients with typical symptoms. They were found to be older, had a shorter history of symptom onset, worse anxiety scores, and more endoscopic findings compatible with gastritis. Proximal extension of acid during the reflux episodes in patients with GERD presenting with NCCP may play a role in symptom generation.

Methotrexate treatment in pediatric Crohn disease patients intolerant or resistant to purine analogues.

BACKGROUND: Immunomodulatory drugs play a major role in maintaining remission and steroid sparing in children with Crohn disease. Although thiopurine agents are commonly used, unresponsiveness or intolerance to these drugs is common. The efficacy of methotrexate in maintenance of remission has been shown in adult Crohn disease; however, pediatric data are limited. Our goal was to evaluate the efficacy and safety of methotrexate in induction and maintenance of clinical remission in children with active Crohn disease who failed thiopurine treatment. PATIENTS AND METHODS: In a retrospective multicenter study, efficacy of methotrexate in inducing and maintaining remission or response was assessed by Harvey-Bradshaw activity index, paediatric Crohn disease activity index and steroid use, in 25 children with Crohn disease, refractory or intolerant to thiopurine analogues. RESULTS: Crohn disease was diagnosed at a mean age of 11.1 +/- 3.1 years and methotrexate was initiated at age 14.5 +/- 3.1 years. The median methotrexate dose was 12.5 mg/m2. Remission was achieved in 16 patients (64%), and response in 6 patients (24%). Out of 18 patients treated for longer than 6 months, 83% were in remission or response after 12 months of treatment. The mean duration of remission and response was 10.8 +/- 8.8 months. Steroid withdrawal was possible in 12/16 patients (75%) receiving steroids at methotrexate introduction. Adverse effects were observed in 6 patients (24%) including nausea and vomiting in 3, elevation of liver enzymes in 2 and pancreatitis in 1 patient. CONCLUSIONS: Methotrexate is beneficial in maintaining remission and steroid-sparing treatment in children with Crohn disease following failure of thiopurine therapy.

Evidence for aberrant regulation of MAP kinase signal transduction pathway in peripheral blood mononuclear cells in patients with active celiac disease.

BACKGROUND: Aberrant signaling via the p21/mitogen-activated proteins (MAP) kinase pathway has been described in lymphocytes of patients with various autoimmune diseases. There is little published data about the intracellular mediators and signals that regulate expression and activity of transcription factors and their effect on celiac disease induction and progression. AIM: To investigate the possible involvement of MAP kinase pathway in peripheral blood mononuclear cells (PBMC) in celiac disease and its correlation with disease activity. METHODS: Expression of the total and activated forms of two MAP kinases [extracellular response kinase (ERK) and c-Jun amino terminal kinase (JNK)] were studied by Western blots in PBMC of 17 untreated and 19 treated celiac patients, and 17 controls. Seven of these untreated celiac patients were studies before and after 6 months of gluten-free diet. RESULTS: Phosphorylated ERK of active celiac disease patients was significantly lower compared with controls (P < 0.01) and was increased towards normal after 6 month of gluten-free diet (P < 0.01). Phosphorylated JNK was increased significantly in the untreated celiac group (P < 0.01) and normalized towards the control level after 6 months of gluten-free diet (P < 0.04). CONCLUSIONS: Aberrant MAP-kinase pathway activity is associated with active celiac disease (CD). Further studies should examine the potential role of this aberration in pathogenesis of CD.

Safety, tolerability and efficacy of a novel self-use biodegradable device for management of obesity.

OBJECTIVE: Obesity is a major public health issue with significant impact on quality of life, morbidity and mortality rates. It is estimated that if the current trends continue, 18% of men and 21% of women worldwide will be obese by 2025. All the current therapies are not optimal due to limited efficacy or safety; thus, there is a need for additional devices for the treatment of obesity. This study aimed to examine the safety, tolerability, and efficacy of a biodegradable encapsulated Epitomee device for weight loss. The technology is based on absorbent pharmaceuticals polymers and bonding materials that self-expand in the stomach to create a pH-sensitive super absorbent gel structure for weight loss. METHODS: A prospective, 12-week twice daily use of the encapsulated device in patients with body mass index of 27-40 kg m-2. Efficacy endpoints were the percent total body weight loss (%TBWL), proportion of participants with 5% TBWL and changes in cardio-metabolic markers. Safety analysis included evaluation of adverse events, laboratory and endoscopic findings. RESULTS: Overall, 52 patients completed the study. TBWL per intension-to-treat analysis was 3.68 ± 3.07% (3.23 ± 2.69 kg) and 4.52 ± 2.97% (3.95 ± 2.57 kg) per protocol. No device serious adverse effects reported. The most common adverse events were headache (18.1%), viral infection (11.5%), abdominal discomfort (10.1%), bloating (7.9%), nausea and constipation (5% each) and flatulence (4.3%). Endoscopy in 26 patients revealed mild, asymptomatic gastric/duodenal erythema without erosions in five patients. CONCLUSIONS: Twelve weeks of Epitomee capsules treatment combined with lifestyle counselling resulted in 3.68-4.52% of TBWL. With continued research, the Epitomee capsules have considerable potential to become a non-invasive, safe and effective treatment option for weight loss.

Antiplatelet therapy and the risk of bleeding induced by gastrointestinal endoscopic procedures. A systematic review of the literature and recommendations.

Antiplatelet drugs may increase the risk of bleeding induced by gastrointestinal endoscopic procedures. The antiplatelet effect of cyclooxygenase-1 inhibitors lasts less than 4 h. Skin and colonic bleeding times are prolonged for 3 and 5 days after aspirin and ticlopidine withdrawal respectively. Major bleeding from endoscopic biopsies is extremely rare. In the four recent largest series, the general incidence of polypectomy-induced major bleeding was 0.11-0.42%. In more than half of the cases the bleeding was delayed, usually up to 2 weeks after the endoscopy. Although three retrospective studies suggested that aspirin does not increase the risk of polypectomy-induced bleeding, the power of these studies is limited. Similarly, it is difficult to draw conclusions from the two studies that assessed the risk of aspirin use during sphincterotomy. Aspirin withdrawal may be harmful in susceptible patients, mainly if it is for more than 7 days. There is no indication to stop aspirin before esophagogastroduodenoscopy, which may reveal aspirin-induced lesions. We recommend discontinuation of aspirin 4-7 days (according to the cardiovascular risk) before other endoscopic procedures. When aspirin is indicated for primary prevention, it can be resumed 14 and 10 days after polypectomy and sphincterotomy respectively. In cases of secondary prevention, it should be resumed after 1 week.

Chronic hepatitis C infection in children.

Hepatitis C virus infection may differ in the pediatric age group with respect to transmission, natural history and response to treatment. Most infected children develop chronic hepatitis but with a relatively mild course of the disease. The most efficient transmission of hepatitis C virus is through direct percutaneous exposure to infected blood or blood products. However, the major risk factor for acquisition of hepatitis C virus in children at present is maternal-infant transmission. The rate of progression to advanced liver disease seems to be more rapid in post transfusional and vertically acquired hepatitis C virus infection than in sporadic hepatitis C virus infection acquired postnatally, or in those without known risk factors. There is a wide variety of histopathological expression, depending on the geographical distribution of the different countries. Treatment for hepatitis C virus in children has not yet been approved. However, combination treatment with peginterferon-alpha-2b with ribavirin shows encouraging results and is generally well tolerated. More randomized controlled trials are needed in the future to optimize the approach to hepatitis C virus infection in children.

Orthotopic liver transplantation reverses the adverse nutritional changes of end-stage liver disease in children.

The changes in growth and body composition after orthotopic liver transplantation (OLT) were studied in 61 children [median age at OLT 3.49 y (range: 0.04-14.5 y), 26 boys and 35 girls] who had survived > or = 1 y post-OLT. Height, weight, midarm circumference (MAC), triceps skinfold thickness (TSF), and subscapular skinfold thickness (SSF) were measured at OLT, 3 and 6 mo later, then annually up to 5 y. SD scores (SDS) were derived from population standards. Results are reported as mean SDS +/- SEM. At OLT the children were short and malnourished (height: -0.98 +/- 0.22; weight -0.82 +/- 0.18; MAC: -1.77 +/- 0.21; TSF: -1.27 +/- 0.17; SSF: -1.49 +/- 0.17). By 3 mo post-OLT, there was a sustained improvement in MAC (-0.73 +/- 0.22), TSF (-0.48 +/- 0.18), and SSF (-0.50 +/- 0.18). Weight SDS (-0.48 +/- 0.20) improved by 6 mo without significant change in height SDS. The three children with Alagille syndrome were smaller (height, weight, and MAC) than children with other diagnoses but did show catch-up growth. Fulminant hepatic failure was not associated with growth failure before or after OLT. Infants (n = 14) were smaller and more malnourished at OLT (smaller skinfold thicknesses and lower weight SDS) than those who received transplants at an older age. By 1 y post-OLT, the only persisting difference was in TSF. Abnormal liver function at 1 y post-OLT (n = 8) and repeated episodes of steroid-treated rejection (n = 13) were associated with worsening height and weight SDS. The use of tacrolimus for graft salvage from rejection (n = 6) was not associated with growth failure. In conclusion, end-stage liver disease has a more adverse effect on MAC, TSF, and SSF than on height and weight, but a marked and rapid improvement occurred post-OLT. Children who were most severely malnourished and growth restricted at the time of OLT showed the greatest catch-up growth after OLT.

Screening for carriers of Tay-Sachs disease in the ultraorthodox Ashkenazi Jewish community in Israel.

A screening program for the detection of Tay-Sachs disease (TSD) carriers in the ultra Orthodox community of Ashkenazi Jews has operated in Israel since 1986. The purpose of this program is the prevention of marriages of 2 heterozygotes. The screened individuals are mostly couples in the engagement process or students in religious high schools. Two mandatory requirements guide this program. First, anonymity of the tested individuals who are identified only by code numbers; second completion of the test results of couples in the engagement process within a few days. The screening program is performed by the determination of hexosaminidase A (Hex A) activity in serum which is repeated in serum and leukocyte extracts in couples where both partners were found in the heterozygote range in the initial tests. The minimal carrier frequency was estimated to be 1:26 or higher, which is higher then in the general Jewish Ashkenazi population. This higher carrier frequency apparently stems from the fact that most members of this community originate from central Europe where the TSD carrier frequency was previously reported to be the highest in the Ashkenazi population. Since the beginning of the screening program no TSD child has been born to newlywed couples of this community in Israel.

Superoxide dismutase activity in duodenal ulcer patients.

OBJECTIVE: To investigate whether duodenal ulcer (DU) is associated with increased free radical generation at the site of ulceration and to attempt, indirectly, to confirm the hypothesis by determining activity of free radical scavengers such as superoxide dismutase (SOD). STUDY DESIGN: Prospective study comparing SOD activity in biopsies taken from the ulcer edge, and antrum in DU patients before and after one month of treatment to SOD activity in biopsies from the duodenal bulb and antrum in a control population. SETTING: Institute of Gastroenterology of a university hospital. STUDY POPULATION: Twenty-five patients with DU. The diagnosis was confirmed by endoscopy. MEASUREMENTS: SOD activity in biopsy specimen, red blood cells (RBC) and serum was measured using the cytochrome c method by spectrophotometry and expressed as U SOD/mg protein. Helicobacter pylori was diagnosed by the rapid urease test (CLO test) from antral biopsies. RESULTS: SOD activity was markedly depleted in the ulcer edge (2.78 +/- 0.9 U SOD/mg protein) as compared to the same patients after one month of treatment (4.59 +/- 2.2 U SOD/mg protein) (P = 0.05) and to biopsies from the duodenal bulb in control population (6.7 +/- 2.4 U.SOD/mg protein) (P = 0.05). SOD activity in the antrum of both groups was similar. There was no difference in SOD activity in RBC and serum of both groups. CONCLUSION: Products of free radical reactions are implicated in the pathogenesis of DU disease. SOD, which is a key enzyme in gastric mucosal protection, is depleted significantly in the ulcer edge compared with controls and increases after healing. However, it is not clear whether this abnormality in oxygen free radical metabolism reflects, rather than causes, the condition which characterizes DU.

Passive smoking in patients with inflammatory bowel disease: an Israeli multicentre case-control study.

BACKGROUND: The association between smoking and inflammatory bowel disease (IBD) is well established. There are, however, no large scale studies of passive smoking in inflammatory bowel disease and this has never been surveyed in the Jewish population of Israel. AIM: To study the passive smoking exposure of Jewish IBD patients in Israel in a large scale multicentre study. METHODS: Patients with established IBD, aged 18-70 years, were interviewed regarding smoking and other habits. Two controls, one clinic and one neighbourhood, matched by age, sex, community group, and education, were sought for each subject. RESULTS: Five hundred and thirty-four patients (273 ulcerative colitis (UC) and 261 Crohn's disease (CD)), 478 clinic controls and 430 community controls were interviewed. There were no significant differences in the passive smoking habits between IBD patients and their controls. Fifty-one percent of UC patients, 50% of the clinic controls and 58% of the community controls were exposed to passive smoking at home (NS); similar results were found among CD patients (50%, 55% and 56%, respectively). When a quantitative exposure index was used UC patients were significantly less exposed to passive smoking than were their community controls (7.46 +/- 8.40 vs 9.36 +/- 9.46, n = 229, P< 0.031). There was no difference in the exposure to passive smoking among CD patients and their controls. No differences in exposure to passive smoking were found when UC patients who had never smoked were compared with their controls. When the quantitative index was used 'never-smoked' CD patients tended to be less exposed to passive smoking at home than their community controls (5.40 +/- 7.60 vs 8.04 +/- 8.72, P < 0.05). CONCLUSION: There is a lack of association between passive smoking and IBD in Jewish patients in Israel. When a quantitative exposure index was used UC patients were found to be less exposed to passive smoking than their community controls.

Measles is more prevalent in Crohn's disease patients. A multicentre Israeli study.

The question whether there is a transmissible pathogenetic agent as a cause for Crohn's disease, remains unanswered. Measles virus has been the subject of many intensive studies, in the attempt to find a role for it in the pathogenesis of inflammatory bowel disease. Whether an early infection with measles virus may predispose to Crohn's disease in later life is still not clear. We conducted a large scale multicentre study, in order to obtain sufficient data to answer this question. To do so, we compared inflammatory bowel disease patients, with Crohn's disease or ulcerative colitis, with two matched control groups: clinical controls, and community controls. A total of 531 patients, 271 with ulcerative colitis and 260 with Crohn's disease were interviewed, as well as 903 matched controls. Blood from 104 inflammatory bowel disease patients and 50 controls was tested for antibodies to measles virus. We did not find any differences related to measles vaccination, either in Crohn's disease or in ulcerative colitis. Exposure to measles in childhood was more frequent in Crohn's disease patients than in their controls, the difference being statistically significant (p < 0.05) in relation to community controls. The presence of IgG antibodies to measles virus was higher in patients with Crohn's disease than in patients with ulcerative colitis or controls (p = 0.084). Another observation of interest was the finding that Crohn's disease patients who had measles in childhood, more frequently had large bowel disease than those who had not had measles. These data lead us to postulate that there may be a role for measles infection in Crohn's disease, even if, at present, this role remains unclear.

Laparoscopically monitored percutaneous endoscopic gastrostomy (PEG) in children: a safer procedure.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) has now become the preferred technique for facilitating enteral nutrition in children with inadequate caloric intake. Because many problems related to PEG insertion have recently been reported, we were motivated to reassess this established technique. We have therefore added a new step--laparoscopic monitoring--to the classic PEG procedure. METHODS: Fifteen children who required PEG during the previous year were studied. Their ages ranged from 2 months to 18 years. Six children were < 1 year old at the time of operation. In 11 patients, the PEG was performed at the end of a laparoscopic Nissen fundoplication. In the others, it was done as a single procedure. RESULTS: In all 15 children, the PEG was performed safely and quickly, without complications. CONCLUSION: The addition of 'laparoscopic monitoring' to the classic PEG procedure introduced by Gauderer et al. changes the first and last parts of the procedure from an almost 'blind' undertaking to a well-controlled and safer procedure.

Type IV 3-methylglutaconic (3-MGC) aciduria: a new case presenting with hepatic dysfunction.

We describe a new patient with type IV 3-methylglutaconic aciduria who presented with a clinical picture simulating a primary hepatic disorder subsequently followed with progressive neurologic impairment and an magnetic resonance imaging picture of Leigh syndrome.

Prevalence of celiac antibodies in children with neurologic disorders.

Neurologic complications are a recognized but unusual manifestation of celiac disease (CD) in adults and children. The use of antigliadin and antiendomysial antibodies in screening has revealed the frequency of CD among symptom-free individuals to be high. Recently, a high frequency (57%) of antigliadin antibodies was demonstrated in adult patients with neurologic dysfunctions of unknown cause. We investigated the yield of screening for CD in children with common neurologic disorders. One hundred sixty-seven children, 1-16 years of age, were included in the study: 41 with migraine headaches, 39 with attention-deficit disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were evident in 22 children (13%) in the study group compared with three children (9%) in the control group. However, in all children, negative IgA and endomysial antibodies were observed; thus duodenal biopsies were not performed. Contrary to studies performed in adults, these results did not demonstrate any relationship between common neurologic disorders without a specific diagnosis during childhood and CD. Thus screening for CD does not need to be routinely included in the diagnostic evaluation of children with these disorders.

Chronic hepatitis B virus in children in Israel: clinical and epidemiological characteristics and response to interferon therapy.

OBJECTIVE: To describe the clinical and epidemiological features of hepatitis B virus infection in Israeli children, and to evaluate their response and compliance to therapy. METHODS: We retrospectively studied 51 patients (34 males, 17 females), aged 2-18 years, from several medical centers in Israel. RESULTS: Of the 51 patients, 38 with elevated transaminase, positive hepatitis B e antigen and/or HBV DNA, and histologic evidence of liver inflammation were treated. Interferon was administered by subcutaneous injections three times a week for 3-12 months (dosage range 3-6 MU/m2). Only 16% were native Israelis, while 78% of the children were of USSR origin. A family history of HBV infection was recorded in 25 of the 51 patients (9 mothers, 16 fathers or siblings). Five children had a history of blood transfusion. The histological findings were normal in 3 patients, 24 had chronic persistent hepatitis, 14 had chronic active hepatitis and 2 had chronic lobular hepatitis. Five children also had anti-hepatitis D virus antibodies. Twelve of the 38 treated patients (31.5%) responded to IFN completely, with normalization of the transaminase levels and disappearance of HBeAg and HBV DNA. In no patient was there a loss of hepatitis B surface antigen. The main side effects of IFN were fever in 20 children, weakness in 10, headaches in 9, and anorexia in 6; nausea, abdominal pain, and leukopenia were present in 3 cases each. The response rate was not affected by age, country of origin, alanine/aspartate aminotransferase levels, or histological findings. However, a history of blood transfusion was a predictor of good response, 60% vs 27% (P < 0.05). CONCLUSIONS: We found IFN to be a safe and adequate mode of treatment in children with chronic HBV infection, regardless of their liver histology and transaminase levels. Therefore, in view of the transient side effects associated with this drug, we recommend considering its use in all children with chronic hepatitis B.

[Groove pancreatitis and adenocarcinoma of the pancreatic head].

A mass within the head of the pancreas causing obstructive jaundice is frequently adenocarcinoma, or infrequently focal pancreatitis. Groove pancreatitis is an inflammation of the head of the pancreas which fills the anatomic space between the head of the pancreas on 1 side and the second part of the duodenum on the other. Obstruction from either cause may cause vomiting, abdominal pain, and loss of weight. It is sometimes impossible to differentiate between the 2 conditions clinically. We present 2 women, aged 41 and 42 years, respectively, with recent onset of diabetes mellitus, obstructive jaundice, abdominal pain and severe loss of weight in whom diagnosis was difficult. In 1 repeated fine needle biopsy directly from the mass did not show adenocarcinoma, but she died of the disease a few months later. The other, in whom malignancy was also suspected, recovered from what was retrospectively diagnosed as groove pancreatitis.

[Percutaneous endoscopic gastrostomy].

Although percutaneous endoscopic gastrostomy (PEG) for feeding purposes has been in use for the past 10-12 years, many practitioners are unaware of this option. We describe 10 patients who underwent PEG with only 1 major, but nonfatal, complication. We stress that PEG is indicated for those who cannot swallow, and is safe, easy to perform, and a relatively cheap procedure. It is therefore a useful substitute for surgical gastrostomy.

Reduced GLP-1R expression in gastric glands of patients with type 2 diabetes mellitus.

BACKGROUND: The incretin effect is reduced in type 2 diabetes mellitus (T2DM) patients. Whether the impaired function of the enteropancreatic axis in these patients is due to defective GLP-1 receptor (GLP-1R) expression in extrapancreatic target organs is not known. AIMS AND METHODS: To compare the GLP-1R expression and distribution in gastric mucosa biopsies of patients with (n =22) and without (n =22) T2DM referred for routine esophagogastroduodenoscopies. GLP-1R mRNA levels were estimated by real-time PCR. The intensity of GLP-1R immunostaining, frequency, and types of glandular cells bearing GLP-1R and their glandular distribution in different stomach mucosa regions were evaluated by immunohistochemical morphological semiquantitative and quantitative analysis. RESULTS: Mean mRNA GLP-1R levels were significantly reduced in patients with T2DM compared with nondiabetic patients (P < .02). Immunohistochemical analysis revealed that the reduced GLP-1R expression in T2DM patients was due to a decreased intensity of immunostaining (P < .01). The number of glandular GLP-1R-bearing cells in both body and antrum mucosa was decreased in T2DM patients. Most notably, the frequency of GLP-1R immunoreactive acid-secreting parietal cells was reduced in the neck area of the gastric principal glands of T2DM patients (P < .01). No correlation was found between the reduced GLP-1R expression and clinical parameters including body mass index, age, glycosylated hemoglobin, and disease duration. CONCLUSION: This is the first evidence of reduced GLP-1R expression in gastric glands of T2DM patients. These data demonstrate that the defective function of the incretin axis in T2DM may also result from decreased GLP-1R expression in its extrapancreatic target organs.

Carriage rate of carbapenem-resistant Klebsiella pneumoniae in hospitalised patients during a national outbreak.

During a national outbreak of carbapenem-resistant Klebsiella pneumoniae (CRKP) in Israel, we conducted a point prevalence survey to determine the extent of asymptomatic carriage. Subsequently, a retrospective case-control study was done, comparing carriers of CRKP with non-carriers, in order to detect risk factors for carriage. Oral, perianal and rectal swabs were obtained from all hospitalised eligible and consenting patients. Selective media for carbapenem-resistant Gram-negative bacteria were used and pulsed-field gel electrophoresis (PFGE) helped to determine clonal source. Culture was obtained from 298 patients. Sixteen (5.4%) were carriers of CRKP, with a higher carriage rate in medical and surgical wards. Only 18% of carriers were treated with any carbapenem prior to the survey. Five of the 16 carriers had a positive clinical specimen for CRKP, hence a clinical infection versus asymptomatic carriage ratio of 1:3. The rectum was the most sensitive site sampled, detecting 15/16 carriers, and the overall sensitivity of the method was 94% with a negative predictive value of 99.6%. In a multivariate analysis of risk factors for CRKP carriage, three variables were significantly related to carriage state: diaper use, longer duration of hospital stay and vancomycin use. PFGE demonstrated that all 16 isolates were identical, confirming clonal origin. A point prevalence survey performed at a single medical centre during an outbreak of CRKP demonstrated a carriage rate of 5.4%. The clonal origin of these isolates suggests that strict adherence to isolation procedure may contain this outbreak.