Ilan Zahavi

Serum transferrin receptor in children and adolescents with inflammatory bowel disease

Abstract Iron studies are difficult to interpret in patients with chronic inflammatory states such as inflammatory bowel disease (IBD). Serum transferrin receptor (TfR) has been reported to be a reliable tool for the diagnosis of iron deficiency in adults. Our aim was to evaluate the role of serum TfR in diagnosing iron deficiency in children and adolescents with IBD. A total of 63 consecutive patients with IBD, aged 9 to 22 years (median 15 years), were tested for serum haemoglobin level, mean corpuscular volume (MCV), and serum iron, transferrin, ferritin and serum TfR levels. Those found to be anaemic were compared with seven age-matched subjects with iron deficiency anaemia (IDA) and 24 age-matched children without signs of anaemia or inflammation. Of the 63 patients with IBD, 26 had anaemia. Based on ferritin levels and MCV indices, anaemia was classified as IDA in 11 patients and as anaemia of chronic disease (ACD) in 15 patients. Mean serum TfR level in normal controls was 3.5 mg/l (range 1.2–8.2 mg/l). Mean (±SD) serum TfR levels were significantly lower in the IBD patients with ACD (5.3 ± 2.3 mg/l) than in the IBD patients with IDA (8.2 ± 3.1 mg/l) (P < 0.05). Serum TfR levels above 5 mg/l identified 10/11 IBD patients with IDA. The calculated TfR/ferritin ratio was 84 (range 17–367) for controls and 133 (range 6.4–1840) for IBD patients. A cut-off level of 350 (91% sensitivity, 100% specificity, 100% positive predictive value, 98% negative predictive value) was established for the diagnosis of IDA in IBD. Conclusion The results suggest that serum transferrin receptor is a useful parameter for the diagnosis of iron deficiency in inflammatory bowel disease, in particular, the transferrin receptor/ferritin ratio with a cut-off level ≥350.

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.

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.

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.

The effect of opiates on the intestinal immune response to cholera toxin in mice

We studied the effect of opiates on the intestinal immunoglobulin A response in mice. C57BL mice were orally immunized by two doses of 10 micrograms of cholera toxin, 2 weeks apart. Experimental groups received subcutaneous injections of morphine, either 10 or 20 mg/kg/day, in two divided doses. Morphine was given for 4 days, starting 1 day prior to each cholera toxin dose. Intestinal secretions were collected by lavage 1 week after the last cholera toxin dose, and assayed for specific anticholera toxin antibody and total immunoglobulin A. Results were expressed as units of anticholera toxin per nanogram immunoglobulin A. It was found that morphine, 20 mg/kg/day, reduced the response from 30.9 +/- 3.11 to 9.78 +2- 1.42 units/ng (M +/- SEM; p less than 0.0001). 10 mg/kg/day of morphine slightly reduced the immune response to 21.38 +/- 3.51 units/ng (M +/- SEM), but failed to achieve statistical significance. Naloxone administration prior to morphine injections abolished the inhibitory effects of morphine. Morphine administration had no effect on the response to a booster dose of cholera toxin 3 months after the initial cholera toxin immunization and morphine administration. It is concluded that morphine has a significant inhibitory effect on the intestinal immune response, but does not effect long-term mucosal immunological memory. The effect is probably mediated by a specific opiate receptor, as it is blocked by naloxone. This effect may have clinical implications.

Activated protein C resistance in pediatric inflammatory bowel disease

BACKGROUND There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohns disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohns disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS One patient with Crohns disease had a positive screen result, two patients (one with Crohns, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohns disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.