Faecal occult blood in children with coeliac disease.

UNLABELLED: 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.

Serum transferrin receptor in children and adolescents with inflammatory bowel disease.

UNLABELLED: 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 > or = 350.

The effect of cisapride on total parenteral nutrition-associated cholestasis in rats.

BACKGROUND: Cholestasis is a frequent problem in patients on total parenteral nutrition. Cisapride has a prokinetic effect on the biliary system, but its effect on hepatic excretory function is unknown. OBJECTIVES: To study the effect of cisapride on TPN-induced cholestasis in a rat model. METHODS: Bile flow and bile salt secretion rate were measured in rats given TPN. There were four groups of 8 to 13 animals each. After a one hour baseline period during which all four groups received i.v. saline infusion, two groups received a TPN solution for another 2 hours, while saline was infused in the two control groups. At the beginning of the second hour, 2 mg/kg cisapride was injected i.v. as a bolus into one experimental and one control group. Bile was collected from the common bile duct. RESULTS: At the end of the third hour, TPN caused a significant reduction in bile flow (P < 0.02) and bile salt secretion rate (P < 0.001) (61.24 vs. 50.74 microliters/min/kg, and 1.173 vs. 0.799 mumol/min/kg, respectively). Addition of cisapride abolished the cholestatic effect of TPN. CONCLUSIONS: Cisapride has a protective effect against TPN-associated cholestasis. This may have clinical significance, and further studies are warranted.

The role of Helicobacter pylori and gastritis in children with recurrent abdominal pain.

BACKGROUND: Recurrent abdominal pain is a common pediatric diagnostic problem. Endoscopy is sometimes performed as part of the evaluation. Although gastritis and/or Helicobacter pylori infection is often present, it is not known if they contribute to the symptomatology. OBJECTIVES: To evaluate the role of either gastritis or H. pylori infection in the symptomatology of children with RAP. PATIENTS AND METHODS: We retrospectively studied two groups of patients, 70 children in each, who had undergone endoscopy. One group was evaluated endoscopically for RAP and the other was a heterogeneous group that underwent endoscopy for indications other than RAP. Biopsies were taken during endoscopy and Giemsa staining was performed for the presence of H. pylori. Triple therapy was given as indicated, and the children were followed for an average of 6 months. RESULTS: Microscopic gastritis was diagnosed in 39 patients (55.7%) of the RAP group and in 31 of the heterogeneous group (44.2%) (NS), and H. pylori was found in 32 patients of the RAP group and in 16 of the heterogeneous group (45.7% vs. 22.8%, P < 0.01). All children with H. pylori, except one in the heterogeneous group, had accompanying gastritis. On the other hand, gastritis without H. pylori infection was seen in 7 children in the RAP group and in 15 of the other. Endoscopy revealed macroscopic abnormalities in 52 of the 70 children with microscopic gastritis. There was a clinical improvement after triple therapy in 28 of 33 children with H. pylori-associated gastritis (84.85%), in 4 of 8 children with gastritis unassociated with H. pylori (50%), and in 8 of 15 without gastritis or H. pylori (53.3%) (P < 0.01 between the H. pylori-associated gastritis and each of the other groups). CONCLUSIONS: H. pylori infection and gastritis may be associated with RAP in a selected subgroup of children. We recommend a complete work-up, including endoscopy and invasive or non-invasive diagnostic modalities for H. pylori, and treatment of the infection.

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.

Adenosine stimulates ANP expression in cultured ventricular cardiomyocytes.

Adenosine protects the ischemic myocardium by coronary vasodilation and the depression of heart rate and contractility, improving myocardial energy balance. Adenosine effects on the myocardium are mediated predominantly by the type A1 receptors. Atrial natriuretic peptide (ANP), a vasodilator and regulator of blood volume, is secreted from either atrial or ventricular myocytes in response to cellular distention. In vivo, adenosine infusion has been shown to induce a rapid increase in plasma ANP, independent of blood pressure. We examined the possibility that adenosine enhances ANP-gene expression in cardiac myocytes. Administration of adenosine (10 microM) to cultured neonatal rat cardiomyocytes led to a 1.7-fold increase (p = 0.014, n = 9) in the abundance of ANP messenger RNA (mRNA) within 30 min, as measured by Northern blot hybridization. No such increase was obtained when adenosine was coadministered with 8-cyclopentyl-1,3dipropylxanthine (CPX, 10 microM), an adenosine A1-receptor antagonist. Our results point at adenosine as regulator of ANP mRNA level in cardiac myocytes.

Hepatic artery thrombosis in pediatric liver transplantation: graft salvage after thrombectomy.

Hepatic artery thrombosis (HAT) is a devastating complication that may occur after orthotopic liver transplantation (OLT). A higher incidence has been reported in children. Salvage of the graft by thrombectomy has been suggested as an alternative to re-transplantation. In this study we report the outcome of three children who underwent thrombectomy for HAT. Between January 1992 and June 1998, 14 children (< 17 yrs of age) underwent liver transplantation. Three developed HAT (one a whole-liver graft recipient, age 17; two living-related graft recipients, ages 4 and 4.5 yr). In the first patient, thrombosis of the hepatic artery was associated with scattered areas of parenchymal necrosis on computed tomography. In the two living-related patients, HAT was found incidentally during re-exploration for bleeding (day 2 and day 10). Thrombectomy was performed in all three patients. At 18-24 months after thrombectomy, all three children had normal graft function. In the first patient, complete regeneration of the liver has been documented by computed tomography and a late asymptomatic recurrent thrombosis is suggested by absence of arterial flow on Doppler examination. The hepatic artery is patent in the two living-related recipients. One of these living-related recipients developed ischemic bile duct stricture and underwent successful percutaneous balloon dilatation. We conclude that long-term normal graft function can be achieved by thrombectomy in pediatric liver recipients with HAT, even in the presence of limited parenchymal damage.

Effect of three days starvation on the phagocytic activity of rat peritoneal macrophages.

To examine the effect of starvation on the phagocytic activity of rat peritoneal macrophages, 8 animals were kept for 3 days on water supply only. The cells showed an increased capacity for superoxide anion production and a marked decrease in their ability to engulf latex particles. The corticosterone level of the fasting animals was markedly increased, an observation suggesting that the alteration of macrophage function could be hormonally mediated. The findings in the present study indicate that the decreased phagocytic capacity of peritoneal macrophages following starvation may be one of the factors responsible for the increased susceptibility to infections in malnourished individuals.

Management of acute gastroenteritis in children in Israel.

OBJECTIVE: Diarrheal diseases are a major cause of morbidity and mortality worldwide. Guidelines about the use of oral rehydration solutions (ORS) and dietary management of acute gastroenteritis (GE) were recently revised and published by the American Academy of Pediatrics (AAP). Study aims were to examine Israeli pediatricians' knowledge and implementation of the revised AAP guidelines, the effect of medical school (Israeli versus foreign medical graduates) on the physicians' practice, and the effect of the type of practice (community vs hospital-based) on the management of gastroenteritis. METHODS: A multiple-choice, written questionnaire was distributed at two pediatrics annual meetings. RESULTS: A total of 87 pediatricians completed the questionnaire. They were aware of 73% of the current AAP guidelines and followed 60% of the guidelines. Most pediatricians (83%) use ORS for treatment of dehydration in GE, but 60% of pediatricians believe that full-strength feeds are inappropriate in the presence of GE, and 67% of them do not recommend full-strength formulas. In addition, 37% of the pediatricians stop feeding temporarily in the presence of GE, in contrast to the 1996 AAP guidelines. There were no differences in knowledge and management practices among pediatricians graduating in Israel, Europe, or the United States, and no differences between pediatricians working in an ambulatory setting or in a hospital. CONCLUSIONS: Pediatricians in Israel, regardless of country of origin, medical school, or place of practice, are aware of the correct use of ORS but do not follow nutritional practices recommended recently by the AAP. These findings suggest that steps for implementing the guidelines are needed in Israel and most probably worldwide.

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 Crohn's 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 Crohn's 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 Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's 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.

In vitro modulation of activation antigens on human lymphocytes by beta-estradiol.

PROBLEM: The possible in vitro immunomodulating effect of beta-estradiol on phytohemagglutinin-stimulated human lymphocyte cultures was studied. METHOD OF STUDY: Lymphocyte cultures from 12 healthy men and women aged 25-35 years were set up for 12 hr in the presence and in the absence of beta-estradiol, and the expression of the activation markers CD25, CD69, and CD71 was examined by flow cytometric analysis with specific fluorescent conjugated antibodies. RESULTS: Although the number of cases is small, in 10 of 12 cases in the presence of beta-estradiol in two different concentrations, a significantly decreased expression of CD69 could be observed. A slight decrease could also be observed for the Interleukin-2 receptor expression; however, the difference, in the presence or absence of beta-estradiol, was not significant. CONCLUSIONS: The results suggest that in vitro addition of beta-estradiol can inhibit, to a certain degree, specific activation markers on phytohemagglutinin-stimulated lymphocytes from young men and women. The present study could not define the role of sex differences because of the small number of samples. A comparison between men and women at various ages in a greater number of cases, as well as studies on activation markers after treatments with estrogens, would be useful.

Elevated serum ferritin level in acute myocardial infarction.

Serum ferritin level was determined in 20 patients with acute myocardial infarction (AMI) during the first 10 days post infarction. Starting on the second day, a gradual increase in serum ferritin level was detected, reaching a maximum of four times the initial level on the sixth day after the infarction. In addition, a significant increase in ferritin content was found in the peripheral blood monocytes on the fifth day after the event. The control group comprised six patients suffering from chest pains not due to AMI. In all of them the serum ferritin level was found to be within normal limits. Peripheral blood monocytes derived from healthy individuals incubated with hydrocortisone, showed a significant enhancement of their ferritin content, a finding suggesting that these cells activated by steroids during stress could be a source of the increased serum ferritin level following AMI. It is concluded that measurement of serum ferritin may be used as a complementary tool for confirming the diagnosis of AMI.

Plasma fibrinogen in Israeli Moslem and Jewish school-children: distribution and relation to other cardiovascular risk factors. The Petah Tikva project.

Plasma fibrinogen levels were measured in 1,175 Israeli schoolchildren, aged 9-18 years, originating from diverse ethnic groups. The Moslem children displayed striking differences in levels and age-patterns of fibrinogen compared to Jewish children. Lower mean plasma fibrinogen levels in boys aged 9-10, 13-14 and 16-18 were observed among Moslem boys, compared to their Jewish counterparts born in Israel. Moslem girls showed lower levels of fibrinogen than Jewish Israeli girls at ages 9-10 and 16-18. While the Jewish children displayed an age-associated fibrinogen pattern comparable at the three age groups, the levels for Moslem children increased pre-puberty and decreased post-puberty, peaking at 13-14 years. No significant difference in mean plasma fibrinogen was found between sexes within ethnic groups. A number of statistically significant but low correlations (-0.32 to 0.24) were found between plasma fibrinogen and high density lipoprotein cholesterol (HDL-C) as a percentage of total cholesterol, triglycerides, blood glucose, uric acid, blood pressure, Quetelet index and sports activity. The difference between fibrinogen levels might point to a possible ethnicity risk factor explanation rather than environmentally acquired factors.

The choleretic effect of nonsteroidal anti-inflammatory drugs in total parenteral nutrition-associated cholestasis.

Cholestasis is a frequent problem in patients on total parenteral nutrition (TPN) therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, cause choleresis in animals. We studied the effect of aspirin on bile flow and bile salt secretion in TPN-associated cholestasis in rats. Four groups of 6-10 animals each received either 154 mM NaCl (saline) or 2.5% amino acid solution (TRAVASOL, Travenol, Israel) and 10% glucose i.v. (TPN) for 3 h. During the second and third hours, taurocholate, the main bile salt in rats, was infused at a rate of 10 micromol/min per kg to prevent bile salt pool depletion. Aspirin, one of the main NSAIDs, was infused during the last 2 h into animals with or without TPN treatment at a rate of 100 mg/kg. Bile was directly collected from the common bile duct for 3 h. Rats given TPN showed a significant reduction in bile flow and bile salt secretion rate compared to control groups: 20.89 vs. 29.60 microl/min per kg (P <0.02) and 0.37 vs. 0.65 micromol/min per kg (P <0.0001), respectively. Aspirin had a significant choleretic effect and was able to overcome the bile flow and bile salt secretion rate reduction caused by TPN; 33.07 vs. 20.89 microl/min per kg (P <0.002) and 0.66 vs. 0.37 micromol/min per kg (P <0.0001), respectively. These results may have clinical implications for TPN-associated cholestasis.

Long-term prognosis of patients after a Q wave compared with a non-Q wave first acute myocardial infarction. Data from the SPRINT Registry.

UNLABELLED: OBJECTIVE, DESIGN AND PATIENTS: Between August 1981 and July 1983, 5839 consecutive myocardial infarction patients were hospitalized in 13 coronary care units in Israel. The present study examines 10 year survival among 4037 consecutive patients with a first myocardial infarction with either Q or non-Q waves. Demographic and medical data were collected from hospital records, and 1 year clinical follow-up was complete for 99% of hospital survivors. Mortality follow-up was extended to June 1992 (mean 10 years of follow-up). RESULTS: Five hundred and eighty patients (14%) had first myocardial infarctions of the non-Q wave type and 3457 of the Q wave type. Hospital mortality was significantly higher in patients with a Q wave (10%) than those with a non-Q wave myocardial infarction (7%) (P < 0.05). One year post-discharge, non-fatal reinfarction and mortality rates were comparable in patients with Q wave (4% and 7%) and non-Q wave myocardial infarctions (4% and 7% respectively). Similarly, 5 to 10 year post-discharge mortality rates were equally high in patients with a non-Q wave (26% and 44%) as in those with a first episode of a Q wave myocardial infarction (22% and 40% respectively). CONCLUSIONS: Patients with a first non-Q wave acute myocardial infarction exhibited relatively better in-hospital survival than counterparts with a first Q wave infarction, but the advantage did not persist after discharge. Patients with a non-Q wave infarction deserve particular attention as their post-discharge mortality risk is similar to counterparts with a first Q wave myocardial infarction.