Yoram Rosenbach

Long-term outcome of tumor necrosis factor alpha antagonist's treatment in pediatric Crohn's disease

BACKGROUND Anti tumor necrosis factor alpha (TNFα) agents have become widely used in pediatric inflammatory bowel disease (IBD). So far, only few studies examined the long-term results of anti-TNFα treatment in children with IBD. METHODS The long-term outcome of pediatric patients with IBD was assessed retrospectively in a multicenter cohort of children treated with anti-TNFα beyond induction treatment. Short- and long-term response rates, predictors for loss of response, data on growth and laboratory parameters were assessed. RESULTS 120 patients [101 crohns disease (CD), 19 ulcerative colitis (UC) or indeterminate colitis (IC)] received either infliximab or adalimumab. The mean age at initiation of anti-TNFα was 13.4 ± 3.9 years and the median duration of anti-TNFα treatment was 15 months (range: 2-90). Overall, 89% of the cohort experienced short-term response following induction. Response was associated with improvement in weight and BMI Z-scores (p<0.001) but not with linear growth. Responders experienced a significant decrease in erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) during treatment (p<0.001). Albumin and hemoglobin both improved but only albumin increased significantly (p<0.001). The cumulative probability of losing response to anti-TNFα treatment was 17%, 38%, and 49% after 1, 3, and 5 years, respectively. Responders had a significantly lower weight and BMI Z-scores at initiation of anti-TNFα treatment in compared to non-responders (p=0.04 and 0.02 respectively). CONCLUSIONS Our long term cohort supports the current evidence on the effectiveness and safety of anti-TNFα treatment in children with IBD. Response to treatment was interestingly associated with lower weight and BMI.

Naloxone is protective against indomethacin-induced intestinal ulceration in the rat

Naloxone, an opiate antagonist, was reported to protect against stress ulcers in dogs and rats. We studied its possible protective effect against indomethacin-induced intestinal ulceration in the rat. Naloxone was indeed found to possess a marked protective effect on the intestinal mucosa (ulcer index 73.3 +/- 13.6 vs. 273.8 +/- 21.8, p less than 0.001). Naloxone was found to elevate basal intestinal mucosal prostaglandin E2 (p less than 0.001) and cyclic adenosine monophosphate levels (p less than 0.005) but was unable to overcome the inhibition of prostaglandin E2 caused by indomethacin. An increase of cyclic adenosine monophosphate levels was seen, however, even in the presence of indomethacin, suggesting that cyclic adenosine monophosphate, but not prostaglandins, may play a role in the protective effect of naloxone.

Spontaneous Normalization of Anti-Tissue Transglutaminase Antibody Levels Is Common in Children with Type 1 Diabetes Mellitus

BackgroundThe prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5–10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up.AimThis study was prompted by the observation that elevated anti-TTG antibody levels in diabetic children may spontaneously normalize despite continued consumption of gluten. The objective of the study was to investigate the prevalence of this phenomenon and associated factors.Materials and MethodsThe files of all children diagnosed with type 1 diabetes mellitus from 2003–2009 at a tertiary pediatric medical center were reviewed for those with elevated serum levels of anti-TTG antibody. Clinical, medical, laboratory, and treatment data were collected. Findings were compared between patients diagnosed with celiac disease and patients with initially elevated anti-TTG antibody levels that spontaneously normalized.ResultsForty-eight of the 738 patients with type 1 diabetes attending our center (6.5%) had elevated anti-TTG antibody blood levels. Celiac disease was diagnosed in 23, and anti-TTG antibody levels normalized in 17 (35.4%), all of whom consumed gluten. At one-year follow-up, there was no significant difference between the groups in HbA1c level or change in anthropometric measurements.ConclusionPhysicians treating children with type 1 diabetes and mildly elevated anti-TTG antibody levels might consider 12-month serologic follow-up on a gluten-containing diet rather than immediate duodenal biopsy.

Short Stature as the Major Manifestation of Celiac Disease in Older Children

Celiac disease was diagnosed by jejunal biopsy and response to gluten elimination in 11 of 23 children with short stature referred after negative endocrine evaluation. The mean age of the group was 11 years, with a range of 5-16. All had been followed for a mean of 2.5 years at a large pediatric endocrine clinic for the evaluation of growth retardation. Bone age retardation of more than 25 percent of the chronologic age was found in all children. Microcytic anemia and past history of gastrointestinal problems were typical of the celiac group but were not documented in the nonceliac patients. Stool fat excretion was a specific but insensitive test, while the 1-hour blood xylose test was of no value in differentiating between the two groups. Close cooperation between pediatric endocrinology and gastroenterology clinics may be fruitful in the identification of celiac patients, especially in a group of older children with short stature, bone age retardation, and microcytic anemia.

The Role of Duodenal Bulb Biopsy in the Diagnosis of Celiac Disease in Children

Background and Study Aims It is suggested that for celiac disease (CD) diagnosis, biopsies should also be taken from the duodenal bulb. Whether bulb biopsies suggestive of CD can be found on upper gastrointestinal endoscopy (EGD) done for reasons other than CD diagnosis is not clear. The aim of our study was to evaluate the contribution of routine bulb biopsies to the diagnosis of CD, when taken regardless of prior suspicion of CD. Methods The study included 96 children who underwent EGD for suspected CD and a control group of 69 children who underwent EGD for reasons other than CD. The mucosal changes were evaluated using the Marsh-Oberhuber classification. Results Among the 87 children diagnosed with CD, we identified 6 patients (7%) with typical histologic findings only in the bulb (Marsh 3), but also 1 patient (1.1%) with findings only in the distal duodenum (Marsh 2). In 20 patients (23%) the histological changes were more severe in the bulb. One patient had more prominent findings in the second part of the duodenum. None of the control patients had histological changes compatible with CD in the bulb or the second part of the duodenum. Conclusions Our findings suggest that when CD is suspected, biopsies should be taken from both locations (bulb and second part) as mucosal changes may emerge only at one site. Nevertheless, the presence of characteristic histology on duodenal bulb biopsies might be sufficient for the diagnosis of CD.

Faecal occult blood in children with coeliac disease.

Abstract It has recently been suggested that in adults with coeliac disease, faecal blood loss may play a role in the development of iron deficiency. A group of 45 children diagnosed with coeliac disease during 1996 and 1997 were therefore prospectively evaluated for the presence of gluten in their diet, iron deficiency anaemia, and faecal occult blood. Sixty children admitted for elective surgery or asthma served as controls. Faecal occult blood was found in four iron deficient children on normal diet, of whom three were newly diagnosed. Occult blood loss disappeared in three of the four children when gluten was removed from their diet. Faecal occult blood was found in 26.7% of children on gluten-containing diet, but not in children on gluten-free diet (P=0.01), or in control children (P=0.001). Conclusion Our data suggest that the incidence of occult blood loss in coeliac disease occurs mainly in newly diagnosed cases and responds to a gluten-free diet. Occult blood testing may not be warranted in the absence of iron deficiency anaemia nor in children with iron deficiency anaemia who are on a gluten-free diet.

Sucralfate Is Protective against Indomethacin-induced Intestinal Ulceration in the Rat

The therapeutic effects of sucralfate on ulcerated gastric and duodenal mucosa is well known. There is, however, very little information about its effect on the mucosa of the small intestine. We studied the possible protective effect of sucralfate against indomethacin-induced intestinal ulceration in the rat. Sucralfate was found to possess a marked protective effect on the intestinal mucosa (ulcer index 23.16 +/- 6.58 vs. 225 +/- 36.37; p less than 0.001). Sucralfate elevated basal mucosal prostaglandin E2 generation (p less than 0.001), and partially overcame the inhibition of prostaglandin E2 synthesis caused by indomethacin (p less than 0.03), but had no effect on mucosal cAMP level. The effect of sucralfate on prostaglandin E2 content might partially explain its protective effect on the intestinal mucosa.

Effect of sucralfate on experimental colitis in the rat

The therapeutic effect of sucralfate on ulcerated gastric and duodenal mucosa is well known. There is, however, almost no information about its activity in colitis. Experimental colitis was produced in rats by rectal instillation of 1 ml of 10 percent acetic acid, and 1.5 ml of a 20 percent suspension of sucralfate was then administered every 12 hours for various lengths of time. Study animals and appropriate controls were killed after 3, 7, 10, or 14 days. The distal colons were studied macroscopically and histologically. Colonic prostaglandin E2 levels were measured in animals killed after 3, 7, 10, or 14 days. The macroscopic score was significantly improved 10 and 14 days after induction of colitis, although the histologic appearence was unchanged. Acetic acid administration increased and sucralfate treatment reduced prosta-glandin E2 levels in colitic animals on days 3 and 7, but not later. The present study supports a role for sucralfate in the treatment of colitis, but further studies on the mechanism of its effect and on its clinical activity are indicated.

Pathologic childhood aerophagy: an under-diagnosed entity

Three children with pathologic childhood aerophagy are described. This entity is characterized by progressive abdominal distension during the day, non-distended abdomen in the morning, and visible air swallowing. The condition is usually self-limited, and treatment is symptomatic and by reassurance. Early recognition and diagnosis of this condition might help avoid unnecessary and expensive diagnostic investigations.

Cricopharyngeal dysfunction in childhood: treatment by dilatations.

A 3-year-old child with Cricopharyngeal dysfunction is reported. Swallowing difficulties, nasal regurgitation, and gagging developed at 2 months of age. Repeated aspirations and over 40 episodes of pneumonia necessitating multiple hospitalizations occurred up to 2 years of age, along with pharyngcal pooling of saliva and inability to swallow solid food. Barium was held up at the Cricopharyngeal level, and a prominent esophageal impression was seen at the same level. Symptoms were completely alleviated after two esophageal dilatations by mercury dilators, and the relief persisted for the 6 months of follow-up. The diagnosis of Cricopharyngeal dysfunction is discussed, and the necessity for manometric studies, in the face of often misleading radiologic appearance, is emphasized. It is suggested that early use of esophageal dilatations might prevent prolonged morbidity and afford long-term symptomatic relief.