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Biomedical subjects

Yoram Bujanover

Publications and source records attributed to Yoram Bujanover.

15 recordsLinked to original sources

Long term nutritional rehabilitation by gastrostomy in Israeli patients with cystic fibrosis: clinical outcome in advanced pulmonary disease.

OBJECTIVES: Several studies have shown a linear correlation between nutritional status and pulmonary function in patients with cystic fibrosis. Our study aims were: 1) To evaluate the effect of nutritional supplementation via gastrostomy on nutritional, clinical, and pulmonary parameters, and 2) To identify predicting factors for success of long-term nutritional rehabilitation. METHODS: Twenty-one Israeli patients, aged 8 months to 20 years, underwent gastrostomy insertion from 1992 to 2001. All patients were pancreatic insufficient, and all carried severe mutations (W1282X in 62% of the patients). Anthropometric and clinical data were obtained for each patient: 0-12 months before and 6-12 months and 18-24 months after gastrostomy placement. Standard deviation scores (SDS) for height, weight, and body mass index as well as percent of height-appropriate body weight were calculated. RESULTS: The mean percent-of-predicted forced expiratory volume in 1 second (FEV1) decreased significantly during the first year of gastrostomy feeding (n = 16), from 44.2% +/- 13.9 to 41% +/- 13.3 (P = 0.05). However, during the second year of therapy (n = 10), a trend toward improvement was observed (from 39.4 +/- 12.1 to 41.4 +/- 16.1). Weight, and BMI z-scores as well as weight percent-of ideal body weight increased significantly. Height z-score for age decreased during the first year (from -1.9 +/- 1.3 to -2.1 +/- 1.4), However, a trend toward improvement was observed during the second year. A significant correlation was found between the change in weight z-score and height z-score during the first (r = 0.488, P = 0.016) and the second (r = 0.825, P < 0.001) years. There was no difference between compliers and noncompliers regarding height, weight, and BMI either before or after gastrostomy placement. A significant correlation between age at insertion of gastrostomy and improvement in height z-score (r = 0.52, P = 0.016) was observed. Cystic fibrosis related diabetes (n = 8) did not affect the response to supplemental feeding. CONCLUSIONS: We observed a trend toward improvement of pulmonary disease during the second year, and a significant improvement in weight, height, and BMI z-scores. Compliance, diabetes, and young age prior to tube insertion did not predict success of nutritional rehabilitation.

Adolescent↗

5-ASA and lycopene decrease the oxidative stress and inflammation induced by iron in rats with colitis.

BACKGROUND: Supplementation of 5-aminosalicylic acid (5-ASA) and of iron are among the principal therapies in patients with inflammatory bowel disease. Therapeutic iron, as well as heme iron from chronic mucosal bleeding, can increase iron-mediated oxidative stress in colitis. This study was designed to examine the influence of iron supplementation on histological expression and oxidative status relative to 5-ASA treatment and antioxidant treatment. METHODS: Colitis was induced using the iodoacetamide rat model, and rats were divided into different dietary groups of 6 rats each: 1, normal chow diet (control); 2, diet supplemented with iron; 3, iron supplementation and lycopene; 4, iron and Beta-carotene; 5, 5-ASA; 6, 5-ASA and lycopene; 7, 5-ASA and iron; 8, 5-ASA, iron, and lycopene. The animals were killed after 3 days and the weight of the ulcerated area recorded. Mucosal specimens were histologically evaluated. Myeloperoxidase (MPO) was measured to evaluate inflammatory status (U/g). Malondialdehyde (MDA) was measured in colonic tissue ( micro mol/g) and superoxide dismutase (SOD) in erythrocytes to assess the degree of tissue oxidative stress. RESULTS: Significantly more severe colitis, including necrosis, ulceration, and hemorrhage, was seen in colonic biopsies of rats with colitis when iron was supplemented. This pathology was attenuated when iron was given in combination with 5-ASA and/or lycopene. There was no significant benefit from adding Beta-carotene. CONCLUSIONS: Iron supplementation can amplify the inflammatory response and subsequent mucosal damage in a rat model of colitis. We suggest that the resultant oxidative stress generated by iron supplementation leads to the extension and propagation of crypt abscesses, either through direct membrane disruption by lipid peroxidation or through the generation of secondary toxic oxidants. Simultaneous treatment with 5-ASA and/or lycopene minimizes the potential hazard of iron. Therefore, we suggest giving iron supplementation with 5-ASA or lycopene or both.

Animals↗

NOD2/CARD15 mutation analysis and genotype-phenotype correlation in Jewish pediatric patients compared with adults with Crohn's disease.

OBJECTIVES: The allelic variants in the NOD2/CARD15 gene G908R, R702W, and 1007fs are strongly and independently associated with susceptibility to Crohn's disease (CD). Our aim was to compare the NOD2/CARD15 genotype and the genotype-phenotype correlation in Jewish pediatric patients with CD (</=16 years of age) with older patients with CD. STUDY DESIGN: Carrier frequencies of the three variants were determined in 67 children and 144 adults with CD. Variants were detected by using allele-specific polymerase chain reaction and restriction enzyme digestion assay. Demographic and phenotypic characterizations of the patients were determined. RESULTS: The carrier rate of the three NOD2/CARD15-associated variants was 51.5% in children and 37.5% in adults (P=.07). The most prevalent allele variant was G908R (allele frequency 18% in children, 11% in adults; P=.063). Young Ashkenazi patients had the highest allele frequency of G908R, and higher than Ashkenazi adults: 25% and 9%, respectively (P=.003). Children had more family history of inflammatory bowel disease and more inflammatory-type disease, with no relation to variant allele carriage. CONCLUSIONS: G908R allele-variant of the NOD2/CARD15 gene is closely related with the appearance of CD at a young age in Jewish Ashkenazi patients.

Adolescent↗

The month of birth is linked to the risk of Crohn's disease in the Israeli population.

OBJECTIVE: The main objective is to study whether the month of birth is associated with the development of Crohn's disease (CD) in the Israeli Jewish population. BACKGROUND: It was suggested that perinatal exposure to infectious agents may have a role in the pathogenesis of CD. Due to the seasonal nature of some infections, a linkage between birth dates and a risk to develop CD would support such a hypothesis. Previous studies that addressed this question were conducted in Europe and differed in their findings. METHODS: Birth dates of 844 Jewish ulcerative colitis (UC) and CD patients from three medical centers representing the north, central, and the south of Israel were compared with the monthly rates of birth during the same period of time. The standard incidence ratio was used to define the risk to develop either disease according to the month of birth. The Score method was used for the evaluation of seasonality trends. RESULTS: Birth during the winter period in Israel was associated with increased risk to develop CD, whereas birth during the spring was associated with a reduced risk. The Score method for seasonality showed a significant peak during winter time in these patients (z = 2.02, p= 0.021). No such seasonal variation was noted for UC patients. CONCLUSIONS: A seasonal pattern was observed in the risk to develop CD but not UC. The findings may support the involvement of environmental factors in the pathogenesis of CD.

Adult↗

Physicians' attitude toward identification and management of childhood obesity in Israel.

Obesity is a serious health problem, and is becoming increasingly common in affluent societies. In 1998, an Expert Committee published guidelines regarding obesity evaluation and treatment. The purpose of this study was to assess the attitude of primary care physicians in Israel toward diagnosis and treatment of childhood obesity, as related to the recommended guidelines. Primary physicians caring for children and adolescents were asked to complete an anonymous questionnaire including personal and professional details, methods of diagnosis, documentation and treatment of childhood obesity, and familiarity with and implementation of the Expert Committee recommendations. One hundred forty-four physicians, treating approximately 100,000 children monthly, completed the questionnaire. Ninety-four percent were considered to have diagnosed obesity properly. Furthermore, only 19% reported weighing all children examined, while 99% of the physicians suggested some treatment for obesity. The most frequent recommendations for managing obesity were referral to a dietitian (92%), physical exercise (85%), and group treatment (27%). The majority of physicians (78%) were not familiar with the new Expert Committee recommendations regarding obesity treatment. This study suggests that the majority of primary physicians diagnose obesity properly and recommend accepted modalities to manage obesity. A comprehensive program to prevent and treat obesity is recommended to improve the health status of the population.

Adolescent↗

Positive tissue transglutaminase antibodies with negative endomysial antibodies: low rate of celiac disease.

BACKGROUND: Screening for celiac disease is based on the sequential evaluation of serologic tests and intestinal biopsy; an optimal screening protocol is still under investigation. The screening policy of one of the main healthcare providers in Israel (Maccabi) consists of measuring total immunoglobulin A and tissue transglutaminase IgA antibodies and confirming positive results by endomysial antibodies. For IgA-deficient patients antigliadin IgG is measured. OBJECTIVES: To evaluate the use of tTGA as a first-level screening test in patients suspected of having celiac disease METHODS: The results of tTGA and EMA tests over a 3 month period were obtained from the laboratory computer. Letters were sent to the referring physicians of patients with positive tests, requesting clinical information and small intestinal biopsy results. tTGA was performed using an anti-guinea pig tTG-IgA enzyme-linked immunosorbent assay kit. RESULTS: Overall, 2,505 tTGA tests were performed: 216 (8.6%) were tTGA-positive of which 162 (75%) were EMA-negative (group 1) and 54 (25%) EMA-positive (group 2.) Clinical information was obtained for 91 patients in group 1 and 32 in group 2. Small intestinal biopsy was performed in 33 (36%) and 27 patients (84%) in groups 1 and 2, respectively. Celiac disease was diagnosed in 4 biopsies (12%) in group 1 and 23 (85%) in group 2 (P < 0.0001). The positive predictive value was 45% for tTGA and 85% for EMA. CONCLUSIONS: Symptomatic patients with positive tTGA and negative EMA have a low rate of celiac disease compared to those who are tTGA-positive and EMA-positive. Confirmation with EMA is advised when tTGA is performed as a first-level screening for suspected celiac disease.

Adolescent↗

Colonic hydrogen elimination and methane production in infants with and without infantile colic syndrome.

Our objective was to investigate the relationship between demographic factors, nutrition, stool gas production, and the existence of infantile colic (IC) syndrome. Hydrogen and methane production from stool specimens of infants with and without infantile colic was quantified at two separate time points, the age at presentation of colic (<12 weeks) and at >6 months of age. The relationship between demographic variables and IC was also studied. A total of 59 infants with ages ranging from 2 to 12 weeks were enrolled in the study. Of these, 30 infants developed symptoms of colic. No correlation was found between IC and birth weight, gestational age, sex, type of feeding, mean time of feeding, stool frequency, and consistency. There was also no correlation between IC and the parents' age or education or the infant's number of siblings. Analysis of the stool samples revealed that methane was produced at concentrations >2 ppm by 15.3% of the infants at age <3 months and by 46.4% of infants at age >6 months. The mean methane concentrations produced by stool increased with age (0.95 +/- 0.58 ppm at 3 months of age vs 1.29 +/- 0.65 ppm at 6 months of age. There was no difference in stool hydrogen concentration between infants with and without IC. In contrast, the mean methane level at 3 and 6 months of age was higher in infants without IC than with IC, but reached statistical significance only at 6 months of age (0.97 +/- 0.68 vs 0.93 +/- 0.46) (NS) at 3 months of age, and 1.56 +/- 0.55 vs 0.93 +/- 0.62 (P < 0.05) at 6 months of age respectively. Furthermore, infants that produced higher methane levels at 3 and 6 months of age had significantly (p < 0.05) less colic in the first months of life. In conclusions, methane production may play a role in the alleviation of IC. Future studies are needed to confirm our findings.

Colic↗

A comparison of budesonide and prednisone for the treatment of active pediatric Crohn disease.

OBJECTIVES: Budesonide has been found effective in patients with mild and moderate Crohn disease and has been found to cause fewer side effects than prednisone. The use of oral budesonide has not been prospectively evaluated in children with Crohn disease. Therefore, the authors initiated a trial to compare remission and tolerance to budesonide and prednisone in children with mild or moderately active Crohn disease. METHODS: A prospective randomized open controlled 12-week trial was carried out comparing pH modified release budesonide, 9 mg, versus prednisone, 40 mg, in children with active mild to moderate pediatric Crohn disease. RESULTS: Thirty-three patients (20 boys and 13 girls; mean age, 14.3 years) enrolled and completed the study. The groups treated with budesonide and prednisone did not differ by age, onset of disease, location of disease, or disease activity. The remission rate at 12 weeks was 47% in the budesonide treatment group and 50% in the prednisone treatment group. Side effects occurred in 32% and 71% of patients treated with budesonide and prednisone, respectively (P< 0.05). Severity of cosmetic side effects was significantly lower in patients treated with budesonide (P< 0.01). CONCLUSIONS: Remission rates for Crohn disease with budesonide and prednisone treatment in this study were similar. Pediatric patients treated with budesonide had significantly fewer side effects than patients treated with prednisone. Budesonide should be considered an alternative to prednisone in pediatric patients with mild to moderate disease activity.

Adolescent↗

Liver cirrhosis and portal hypertension in cystic fibrosis.

OBJECTIVES: Liver disease is the second cause of death in cystic fibrosis. The most deleterious complication of liver disease is portal hypertension, which has an estimated prevalence of up to 8%. Portal hypertension may manifest itself by splenomegaly, hypersplenism, gastro-oesophageal bleeding and ascites. The aim of our study was to determine the prevalence, risk factors and invasive management of portal hypertension at our centre. METHODS: One hundred and fifty patients with cystic fibrosis were followed up between 1975 and 2000 in the national cystic fibrosis centre in Israel. Forty patients (27%) had liver disease. All underwent clinical evaluation and laboratory and imaging studies. RESULTS: Portal hypertension was diagnosed in 10 patients (7%), of whom eight were male. The mean age at diagnosis was 11 years (range, 4-17 years). All had severe mutations of the cystic fibrosis transmembrane conductance regulator gene (the CFTR gene), pancreatic insufficiency, meconium ileus or distal intestinal obstruction syndrome and variceal bleeding. Seven patients underwent sclerotherapy to control acute bleeding. Four underwent portosystemic shunting (functioning up to 37 years). Two patients with severe lung and liver disease underwent transjugular intrahepatic portosystemic shunting, which provided bleeding control, but both died while waiting for lung/liver transplantation. One patient underwent liver transplantation due to liver failure and still had good liver and lung function 10 years later. CONCLUSIONS: Portal hypertension is more common among Israeli patients with cystic fibrosis. The unique genetic composition of our population may explain this phenomenon. Risk factors include male gender, pancreatic insufficiency, severe CFTR mutations, meconium ileus and meconium ileus equivalent. Sclerotherapy is the main option to control oesophageal variceal bleeding, while portosystemic shunts offer a prolonged alternative treatment for refractory bleeding. A transjugular intrahepatic portosystemic shunt and liver transplantation may also be effective, but further research is required in order to establish their role.

Adolescent↗

Evaluation of oral budesonide for treatment of mild and moderate exacerbations of Crohn's disease in children.

OBJECTIVES: Oral budesonide has been found to be efficacious for mild to moderate Crohn's disease in adults, with equal improvement rates for budesonide and prednisone. We report the results of a retrospective study of budesonide treatment in mild to moderate Crohn's disease in children. STUDY DESIGN: Charts of patients treated with budesonide (n = 62) with a pediatric Crohn's Disease Activity Index of 12.5 to 40 were compared with a cohort of 58 age-matched patients treated with prednisone. RESULTS: Among children treated with budesonide, 48% had remission compared with 77% of the children treated with prednisone (P =.001). Among patients who had failed previous medical therapy with mesalamine, 59% had remission with budesonide (9 mg/day). Remission with prednisone occurred in 73% of children who failed to achieve remission with budesonide. Patients responding to budesonide had significantly milder disease compared with nonresponders who had remission while taking prednisone. CONCLUSIONS: Budesonide is useful in mild to moderate Crohn's disease in children. It is more effective than mesalamine and antibiotics but less effective than prednisone. Budesonide should be considered for first-line therapy in mild to moderate Crohn's disease.

Administration, Oral↗

A possible role of prolactin on growth and maturation of the gut during development in the rat.

The growth and maturation of the gastrointestinal tract during development is influenced by diverse genetic and growth factors. Since prolactin is abundant in amniotic fluid and breast milk, we hypothesized that it may also affect gut development. The effect of prolactin on thymidine incorporation and tissue alkaline phosphatase, maltase and lactase activity was studied on jejunal explants from fetal, newborn and 2 week-old rats. The results were compared with the effects of epidermal growth factor (EGF) under identical experimental conditions. Prolactin induced a significant increase in proliferation and a two- to threefold increase in maltase and alkaline phosphatase activity of the newborn explants. The effect of prolactin in this group compared to that of EGF was significantly greater with respect to proliferation, and almost identical with respect to the hydrolases studied. These results suggest that prolactin might have a role in the process of growth and maturation of the gut mucosa during ontogeny.

Alkaline Phosphatase↗

Chronic hepatitis C in Israeli children.

Natural history, epidemiology, and histopathological features of chronic hepatis C (CHC) are well established in adults. Data on histopathological findings of CHC in children are still limited and controversial. We aimed to evaluate the histopathological features of CHC in children in Israel. We reviewed, retrospectively, 20 liver specimens from 20 children with CHC for inflammation and fibrosis, hepatocyte necrosis, fatty changes, cholestasis, bile duct damage, sinusoidal lymphocytosis, and glycogen storage. The most common histological feature was portal inflammation (95%) and lobular inflammation (70%). Sinusoidal lymphocytosis was present in 85% and glycogen storage vacuoles in 40%. Most of the children (80%) had no fibrosis, 15% had mild fibrosis and 5% moderate fibrosis. Advanced fibrosis or cirrhosis was not found. No correlation was found between the age at biopsy and any of the histological parameters. Our study shows that children with CHC have a different phenotype of liver disease with slowly progressive natural history irrespective of duration of the disease.

Adolescent↗

Divergent patterns of extracellular matrix protein expression in neonatal versus adult liver fibrosis.

The extracellular matrix (ECM) expression is subject to distinct changes during ontogeny, and the natural course of liver fibrosis in neonates is thought to differ from that in adults. We compared the expression and distribution of main ECM components between neonatal and adult liver fibrosis. Liver biopsies from infants with neonatal cholestasis and fibrosis were compared to adult biopsies exhibiting an equivalent stage of fibrosis. All biopsies were examined by immunohistochemistry (indirect ABC method) for the ECM proteins, collagens I, III, IV, and VI, laminin, and fibronectin. Infants (aged 1-8 months) with neonatal hepatitis (n = 3), extrahepatic biliary atresia (EHBA) (n = 5), and normal histology (n = 2) were compared with 9 adults (aged 17-70 years) with chronic hepatitis (n = 3), primary biliary cirrhosis (PBC) (n = 4), and normal histology (n = 2). Collagens I, III, and IV and fibronectin were significantly increased in neonatal hepatitis with mild fibrosis (score < or = 4) compared to adults with an equivalent fibrosis stage. This increase was particularly notable in perisinusoidal spaces. Laminin expression was increased in portal and perisinusoidal spaces both in neonatal hepatitis and extrahepatic biliary atresia with mild fibrosis. In infants with moderate to severe fibrosis (score > or = 6), only collagen I was increased in comparison to adults, whereas collagen VI expression was identical in all groups, irrespective of the degree of fibrosis. Expression of matrix proteins was not different in infants and adults without fibrosis. The increased perisinusoidal deposition of certain ECM components in infants with active hepatitis and mild fibrosis may point to an underlying difference in the mechanism or stimulus of fibrogenesis in neonates as compared to adults.

Adolescent↗