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Biomedical subjects

Raanan Shamir

Publications and source records attributed to Raanan Shamir.

At least 55 records · Page 3Linked to original sources

Assessment of osteoporosis by quantitative ultrasound versus dual energy X-ray absorptiometry in children with chronic rheumatic diseases.

OBJECTIVE: To evaluate the validity of quantitative ultrasound bone sonometry (QUBS) as a screening tool for the diagnosis of osteoporosis in children with chronic rheumatic diseases (CRD), compared to the conventional dual energy x-ray absorptiometry (DEXA). METHODS: Forty children with CRD [32 with juvenile idiopathic arthritis (JIA), 6 with systemic lupus erythematosus, and 2 with dermatomyositis] aged 9.9 +/- 4.3 years, were evaluated by QUBS of radius and tibia and DEXA of the lumbar spine. Twenty-five (62.5%) patients were treated with corticosteroids. Measurements of the velocity of the ultrasound wave, expressed as speed of sound (SOS) in m/s, and the results of the bone mineral density (BMD) assessed by DEXA were compared to reference data from healthy age and sex matched Israeli children. RESULTS: Compared to controls, patients with CRD had significantly lower values by QUBS and DEXA alike. BMD and SOS z scores < -1 SD were found in 45% and 38% of the patients, respectively. Reduced BMD and SOS values correlated with age at disease onset and corticosteroid treatment. BMD alone correlated negatively with disease duration and methotrexate therapy. BMD was significantly lower in patients with polyarticular JIA compared to patients with oligoarticular disease (p < 0.03). SOS values did not differ between subtypes of JIA. A significant positive correlation was found between the lumbar DEXA and radius SOS. CONCLUSION: QUBS evaluation of radius and tibia yielded results comparable to DEXA and may therefore be used for screening patients with CRD for osteoporosis. QUBS might represent a promising means of evaluating bone quality in at-risk children.

Absorptiometry, Photon↗

New supplements to infant formulas.

Foods, which, in addition to their nutritional attributes, contain also elements that are considered to be health-promoting, have been termed "functional foods". In this regard, human milk has gained recognition as being the ultimate functional food for infants - by its biological compatibility, nutritional value and the undisputed added value of its health promoting qualities. Intensive research activity has recently evolved in a quest to identify and define the components of human milk that might confer disease-preventing and health-enhancing properties and to determine the instances and clinical conditions in which these factors become particularly important. The outcome of such research would also provide a rationale for advocating the supplementation of commercial infant formulas with such substances. In effect, the body of data accumulated from scientific and clinical studies on nucleotides, probiotics, prebiotics and long-chain polyunsaturated fatty acids in human milk and as additives to infant formula, has become regarded as convincing enough by the infant formula industry so as to launch into the market formulas supplemented with one or more of these factors - in an effort to emulate human milk and its beneficial effects. The following review is intended for the reader to obtain a general idea of the new supplements that have been introduced to infant formulas. We summarize the pertinent experimental and clinical observations concerning each of the supplements, pointing out their potential specific benefits, their possible disadvantages and the issues that still remain unresolved.

Dietary Supplements↗

Oral insulin supplementation attenuates atherosclerosis progression in apolipoprotein E-deficient mice.

OBJECTIVE: The role of insulin in atherosclerosis progression in diabetes is uncertain. We examined the effects of oral insulin supplementation on atherogenesis in apolipoprotein E-deficient (E(0)) mice. METHODS AND RESULTS: One-month-old male E(0) mice were orally supplemented with human insulin (0.1, 0.5, and 1 U/mL) or placebo for 3 months. At the end of the study, serum and macrophage oxidative stress and atherosclerosis progression were studied. Insulin reduced lesion size by 22% to 37% (P<0.05) in all study groups. Lipid peroxides serum levels were 18% lower (P<0.01), and serum paraoxonase activity was 30% higher (P<0.01) in mice supplemented with 1.0 U/mL insulin compared with controls. Insulin reduced mouse peritoneal macrophage (MPM) lipid peroxides content and superoxide anion release by up to 44% and 62%, respectively (P<0.01). In addition, oral insulin reduced MPM cholesterol content and cholesterol biosynthesis by up to 36% and 53%, respectively (P<0.01). In vitro incubation of E(0) mice MPM with increasing insulin concentrations (0 to 100 micro U/mL) resulted in a dose-dependent reduction of cholesterol synthesis by up to 66% (P<0.05). CONCLUSIONS: In E(0) mice, oral insulin supplementation attenuates the atherosclerotic process. This may be attributable to insulin-mediated reduction of oxidative stress in serum and macrophages as well as reduction in macrophage cholesterol content.

Administration, Oral↗

Advances in celiac disease.

In recent years, it has become evident that CD is much more common than previously appreciated, with a prevalence of 0.5% to 1% in Western, Arabian, and Indian populations. The disease may be present without symptoms (silent CD) or may present with extraintestinal manifestations only. Increasing awareness of the many faces of CD will increase diagnosis rate. CD patients have a cure for their disease, named the gluten-free diet, but this curative measure is very hard to adhere to. With the new insights into the pathogenesis of CD, clinicians enter an era where new treatment modalities for CD may turn into reality.

Autoantibodies↗

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↗

The effect of early treatment in children with chronic hepatitis.

BACKGROUND: The aim of this study was to compare the efficacy of interferon alpha (IFN) or IFN and ribavirin (IFN+RIB) combination therapy in children with chronic hepatitis C (CHC). Most children were infected during treatment for pediatric malignancies. PATIENTS AND METHODS: We reviewed the charts of 20 patients (11 boys and 9 girls) aged 10.6 +/- 3.7 years with CHC who were treated between 1995 and 2001. Seven patients diagnosed with CHC before 1998 were treated with 3 million units of IFN three times weekly for 6 to 12 months. Thirteen children diagnosed after 1998 were treated with 3 million units of IFN three times weekly plus 15 mg/kg of ribavirin daily for 6 months (IFN+RIB). RESULTS: Demographic and clinical characteristics were not different between the two treatment groups. A sustained complete response defined as serum alanine aminotransferase normalization and hepatitis C virus RNA clearance at 6 and 12 months after termination of treatment occurred in three of seven children (43%) treated with IFN monotherapy compared with 7 of 12 children (54%) in the group treated with IFN+RIB combination therapy (not significant). The only difference between responders and nonresponders was the duration of infection before the initiation of therapy, which was significantly shorter in responders (1 +/- 0.3 vs. 5.6 +/- 2.2; P = 0.001). CONCLUSIONS: In this small cohort of children with CHC, early initiation of antiviral treatment was associated with a sustained response rate independent of treatment type. Regular follow-up of children at risk of acquiring hepatitis C virus infection should assist in the early diagnosis. Early initiation of antiviral treatment may improve the rate of sustained response.

Antiviral Agents↗

Nonsyndromic paucity of interlobular bile ducts: report of 10 patients.

OBJECTIVES: Only a few reports of nonsyndromic paucity of interlobular bile ducts (NS-PILBD) have been published. The authors' aim was to outline the clinical and laboratory profile of patients with NS-PILBD diagnosed at a tertiary referral center. METHODS: The authors reviewed all the reports of pediatric liver biopsies performed between 1991 and 2000 at their institution. Upon diagnosis of NS-PILBD, patients' records were examined for clinical, laboratory, and histologic data, and liver biopsy specimens were re-evaluated. RESULTS: Three hundred biopsies were performed in children during the study period, of which 64 were in infants younger than 1 year. NS-PILBD was diagnosed in 10 of 64 (16%) biopsy specimens. Mean age at presentation was 10 days (range, 1 day-6 weeks), and mean follow-up was 4.5 years (range, 1-9 years). An underlying condition was identified in 70% of children with NS-PILBD: namely congenital cytomegalovirus (n = 2), progressive familial intrahepatic cholestasis (PFIC, n = 2), mitochondrial DNA depletion (n = 1), Niemann-Pick type C (n = 1), and arthrogryposis multiplex congenita, renal dysfunction, and cholestasis (ARC syndrome; n = 1). All children presented with jaundice. Four children had initially acholic stools. At their last follow-up visit, failure to thrive was present in five children, and cholestasis in six children. Mortality was noted only in children with metabolic diseases (n = 2). CONCLUSIONS: In the study, NS-PILBD was common in young children undergoing liver biopsy. Although NS-PILBD is nonspecific, a wide survey for inborn errors of metabolism should be included in the diagnostic work-up of NS-PILBD. In the authors' center, the association of certain metabolic diseases with NS-PILBD carries a grave prognosis.

Arthrogryposis↗

Lamivudine treatment for chronic hepatitis B infection in children unresponsive to interferon.

BACKGROUND/AIMS: Lamivudine is a potent inhibitor of hepatitis B virus (HBV) replication. This prospective open study reports the results of lamivudine treatment in children with chronic hepatitis B infection who did not respond to previous interferon treatment. PATIENTS AND METHODS: Lamivudine, 3 mg/kg/day (maximum, 100 mg/day), was given for 52 weeks to 20 children and adolescents, ages 8.5 to 19 years, with chronic hepatitis B infection who had been treated with interferon 2 to 5 years earlier. We evaluated virologic and biochemical responses, the occurrence of YMDD mutants and adverse effects. RESULTS: All children were HBV DNA+, hepatitis B e antigen (HBeAg) /anti-hepatitis B e antibody- at start of treatment. At the end of 1 year, HBV DNA declined by 95% in all patients, and 8 of 18 (44%) had sustained undetectable HBV DNA by hybridization assay. Median pretreatment alanine aminotransferase (ALT) x1.5 upper limit of normal decreased to ALT x0.9 upper limit of normal after 1 year. One child became HBeAg-negative. YMDD mutants were detected in 11 of 17 (65%) children after 1 year of lamivudine treatment. Among children with YMDD mutant variants, 54% maintained normal ALT values and 45% had undetectable HBV DNA by hybridization assay. No adverse effects were observed. CONCLUSIONS: Children with chronic hepatitis B infection treated with lamivudine after failure of interferon therapy had decreased HBV replication and improved ALT values. However, lamivudine treatment resulted in an exceptionally high rate of lamivudine-resistant mutants and low HBeAg seroconversion rate.

Adolescent↗

Influence of oral insulin supplementation on carbohydrate, lipid and protein metabolism in weaned Balb/c mice.

BACKGROUND: [corrected] Insulin is substantially present in human milk. Suckling animal models have demonstrated local trophic effects of insulin on the gut mucosa, but the effects of oral insulin in the post-weaning period are controversial. OBJECTIVE: To examine local and systemic effects of oral insulin supplementation in the post-weaning period. MATERIALS AND METHODS: Balb/c mice received oral insulin supplementation in their drinking water (1 U/ml) from beyond weaning during 40 days (S group). Plasma glucose, lipid levels, amylase and insulin were measured. The liver and intestine were weighed and thiobarbituric acid-reactive substance (TBARS) levels were examined in liver tissue. These data were compared to a control group (C group). RESULTS: Fasting glucose levels (mean +/- SD) were lower in the S than in the C group (116. 5 +/- 10.7 vs 143.9 +/- 25.4 mg/dl; p < 0.001), as were prandial glucose levels (123.1 +/- 12.2 vs 145.1 +/- 18.0 mg/dl; p = 0.03). Plasma insulin levels were higher in the S than in the C group (1,110.28 +/- 721.59 vs 308.17 +/- 100.50 pmol/; p = 0.03). Total triglyceride levels (130.4 +/- 32.4 vs 193.6 +/- 48.4 mg/dl; p < 0.02) and total cholesterol levels (83.6 +/- 5.7 vs 93.3 +/- 7.9 mg/dl; p < 0.05) were lower in the S group compared with the C group. Liver weight was significantly higher in the S group compared with C (0.75 +/- 0.1 vs 0. 7 +/- 0.1 g, p = 0.05). CONCLUSIONS: In the post-weaning period, oral insulin supplementation had a significant effect on plasma glucose levels and lipid profile, as well as on liver weight and protein content in Balb/c mice. The application of these findings in humans should be studied.

Administration, Oral↗

Serum levels of bile salt-stimulated lipase and breast feeding.

OBJECTIVES: Bile salt-stimulated lipase (BSSL) is present in the sera of healthy humans, may affect lipoprotein structure and composition, and reduce atherogenicity of oxidized LDL-cholesterol. Our aims were to examine serum levels of BSSL in breast- and formula-fed infants, and explore the influence of BSSL on serum lipid profile and oxidative status. METHODS: Infants (2-8 weeks old) were prospectively enrolled. Blood was drawn for serum levels of BSSL, total antioxidant status (TAS), and lipid profile. RESULTS: Serum levels of BSSL were similar in breast-fed (0.28 +/- 0.15 microg/l, n = 18) and formula-fed (0.31 +/- 0.09 microg/l, n = 15) infants, and were much lower than reported levels for adults. In breast-fed infants only, BSSL levels were correlated with LDL-cholesterol serum levels (r = -0.53, p = 0.04). Total cholesterol (119.2 +/- 34.3 mg/dl vs 97 +/- 27.2, and p = 0.05) and LDL-cholesterol serum levels (50.5 +/- 26.1 mg/dl vs 33.3 +/- 20.3, p = 0.05), were elevated in breast-fed compared with formula-fed infants, but TAS was similar in both groups (1.02 +/- 0.18 mmol/l and 0.98 +/- 0.12 mmol/l, respectively). CONCLUSIONS: Lack of difference in BSSL serum levels between formula- and breast-feeding, and lower BSSL levels in infants compared to adults, suggest that human milk does not contribute to BSSL serum levels.

Antioxidants↗

The prevalence of low selenium levels in newly diagnosed pediatric cancer patients.

Low selenium (Se) levels have been found in assoiciation with high incidences of various types of adult cancer. Much less is known about this issue among pediatric cancer patients. Forty-two pediatric patients with a variety of newly diagnosed malignancies were divided into two groups, 20 with localized disease (LD) and 22 with widespread disease (WSD). Analysis of serum collected before the commencement of treatment showed that half the patients had low Se serum levels, lower and more common in WSD than in LD. There was no significant difference in the prevalence of low albumin levels among patients with low Se levels, and most of the newly diagnosed children did not suffer from malnutrition. It was concluded that Se deficiency is common among newly diagnosed pediatric cancer patients, Se levels are lower in WSD than LD, and low Se levels are more prevalent in WSD patients than in LD patients.

Adolescent↗

Intradialytic parenteral nutrition in malnourished children treated with hemodialysis.

OBJECTIVE: To examine the feasibility and effectiveness of intradialytic parenteral nutrition (IDPN) in children on hemodialysis. DESIGN: Prospective experimental study with a single intervention group. SETTING: A pediatric hemodialysis unit. SUBJECTS: Four malnourished children on hemodialysis (3 girls and 1 boy) 4 to 18 years of age were studied during a period of 1 year. INTERVENTION: IDPN, which is composed of amino acids (8.5% solution), glucose (as 10% to 15% dextrose), and 20% fat emulsion, was administered at every dialysis session (3 times a week, during 4 hours each time) for 7 to 12 weeks. MAIN OUTCOME MEASURE: Oral caloric intake (evaluated by using a 3-day diet history), dry weight (weight after dialysis), body mass index, percent ideal body weight, total lymphocyte count, and serum levels of albumin before, immediately after cessation of IDPN, and 3 months after cessation of IDPN. RESULTS: Oral caloric intake increased markedly after IDPN administration, from 5 to 63 kcal/kg/d (mean, 33 kcal/kg/d) before IDPN administration to 35 to 177 kcal/kg/d (mean, 86 kcal/kg/d) at the time of cessation. Weight did not change during the treatment period but it did increase from 9.5 to 36.4 kg (mean, 25 kg) to 11 to 39 kg (mean, 26.7 kg) 3 months later. Percent ideal body weight increased from 73% to 88% (mean, 78.5%) to 79% to 90% (mean, 85.1%), and body mass index increased from 12.2 to 15 kg/m(2) (mean, 13.5 kg/m(2)) to 13.4 to 15.5 kg/m(2) (mean, 14.6 kg/m(2)). Total lymphocyte count increased from 538 to 2,041 cells/mm(3) (mean, 1,403 cells/mm(3)) to 724 to 2,884 cells/mm(3) (mean, 2,066 cells/mm(3)). Plasma levels of albumin increased in 1 patient but remained unchanged in others. CONCLUSION: Short-term IDPN treatment may serve as a safe and effective nutritional intervention in malnourished children on hemodialysis.

Adolescent↗

Hypocholesterolemia in children and adolescents with beta-thalassemia intermedia.

OBJECTIVES: To conduct a prospective study to evaluate the lipid profile in children and adolescents with beta-thalassemia intermedia and major, and to examine the contribution of different factors to hypocholesterolemia observed in these patients. STUDY DESIGN: Demographic, clinical, and laboratory data were prospectively obtained from patients with beta-thalassemia intermedia (n = 9) and major (n = 47). Lipid profiles were also determined in a control group of healthy children (n = 18). Lipid values of beta-thalassemics and controls were compared and the relationships between lipid levels and different covariates were determined. RESULTS: beta-thalassemia intermedia patients had significantly lower total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) compared with beta-thalassemia major and controls (P <.001). With regression analysis, serum lipid levels (TC, HDL-C, and triglycerides) correlated with diagnosis (beta-thalassemia major or intermedia) but not with age, sex, hemoglobin, or ferritin. LDL-C was influenced by both diagnosis and ferritin levels. CONCLUSIONS: Children and adolescents with beta-thalassemia intermedia have significantly lower cholesterol levels than patients with beta-thalassemia major. This is related to their disorder and not influenced by age, sex, hemoglobin, or ferritin levels. In these patients, needless investigations for hypolipidemia should be avoided.

Adolescent↗

Use of quantitative ultrasound to assess osteopenia in children with Crohn disease.

BACKGROUND AND AIMS: Children with Crohn disease are at increased risk for osteopenia and osteoporosis. Early development of osteopenia can increase the lifetime risk for fractures and may be amenable to early intervention. The gold standard for measuring bone mineral density (BMD) and fracture risk is dual x-ray absorptiometry (DXA), but this involves some radiation and specialized programs for measuring BMD in children. Bone density Z scores were evaluated with quantitative ultrasound (QUS) using a novel portable device and were compared with DXA in children with Crohn disease. METHODS: Thirty-five children with documented Crohn disease (mean age 14.3 +/- 2.3 years) had speed of sound measured at the left radius and left tibia. Normative values for QUS Z scores were calculated from a cohort of 1,110 healthy children. A subgroup of 26 children with Crohn disease underwent both QUS and DXA. Z scores were calculated and compared for both groups. RESULTS: The mean Z score using lumbar spine DXA was -1.04 +/- 1.51 SD, compared with -0.15 +/- 1.49 SD, using the lowest Z score for QUS ( < 0.05). Using height adjusted DXA, 50% of children with Crohn disease had osteopenia, whereas QUS detected only 19.2% of these children ( < 0.05). Significantly fewer cases of osteopenia were detected using QUS at Z scores up to -2 SD. CONCLUSIONS: Quantitative ultrasound performed on the radius and tibia may not be sensitive enough to pick up osteopenia in children with Crohn disease.

Absorptiometry, Photon↗

The use of a single serological marker underestimates the prevalence of celiac disease in Israel: a study of blood donors.

OBJECTIVES: Recent studies suggest that celiac disease was previously underdiagnosed. To find out whether antiendomysial antibodies underestimate the prevalence of celiac disease, we elected to use a strategy combining multiple serological markers to explore the prevalence of celiac disease in Israel and the usefulness of the various antibodies in screening for celiac disease. METHODS: Serum samples from 1571 healthy blood donors were tested. A small intestinal biopsy was offered to all patients who tested positive for either human tissue transglutaminase antibodies, an ELISA kit based on antiendomysium (EMA-ELISA), immunoglobulin A antigliadin verified by antiendomysial immunofluorescence antibodies, and to patients who were IgA deficient with elevated antigliadin IgG. RESULTS: A total of 59 subjects (3.8% of study population) were offered an intestinal biopsy based on serological findings, and 30 of 59 patients agreed to undergo intestinal biopsy (1.9% of study population). Celiac disease was diagnosed in 10 patients, establishing a prevalence of at least 1:157 in the general population (0.6%, CI = 0.3-1.1%). Using any serological marker alone would have underestimated the prevalence of celiac disease, as it was diagnosed in only two patients who tested positive for endomysial immunofluorescence antibodies (prevalence of 1:786, 0.1%, CI = 0.02-0.5%), six patients positive for tissue transglutaminase (prevalence of 1:262, 0.4%, CI = 0.1-0.9%), and seven patients positive for ELISA-EMA (prevalence of 1:224, 0.45%, CI = 0.2-0.9%). CONCLUSIONS: The prevalence of celiac disease in Israel is at least 1:157 in the general population, confirming its underdiagnosis in previous studies. The disparity between the various serological markers suggest that the use of one serological marker is insufficient for establishing the true prevalence of celiac disease.

Adolescent↗

[Consumption of soy and phytoestrogens--is there a place for dietary guidelines?].

Phytoestrogens (PE), and soy protein consumption are suggested to be associated with reduced risk of developing breast and prostate cancer, slowing the progression of renal failure, improved bone density, reduced serum lipid levels, and reduction in the risk of developing coronary artery disease. In infants, breast milk is the feeding of choice in the first months of life, and soy-based formulas should only be given to infants with intolerance of cows milk protein. In adults, except for reduced serum lipid levels, there is a lack of scientific evidence for health claims related to high phytoestrogen consumption.

Animals↗

ELISA of anti-endomysial antibodies in the diagnosis of celiac disease: comparison with immunofluorescence assay of anti-endomysial antibodies and tissue transglutaminase antibodies.

BACKGROUND: Celiac disease is common in both children and adults. Small intestinal biopsy is mandatory for establishing a diagnosis. Anti-endomysial antibodies, detected by immunofluorescence, have a sensitivity and specificity close to 100% in the diagnosis of CD. Recently, tissue transglutaminase has been identified as the target autoantigen of antibodies against endomysium, and TTG antibodies are comparable to EMA-IMF in the diagnosis of CD. OBJECTIVE: To evaluate a new enzyme-linked immunosorbent assay kit for EMA, compared to EMA-IMF and TTG antibodies in the diagnosis of CD. METHODS: Our study population included all subjects with positive EMA-IMF who underwent intestinal biopsy (n = 21). From the same sera, TTG antibodies and EMA-ELISA were determined, and all antibody results were compared to the biopsy findings. RESULTS: EMA-IMF was able to predict biopsy findings of CD in 19 of 21 cases (90.5%). When patients with biopsy findings compatible with CD and positive EMA-IMF (n = 19) were tested for EMA-ELISA and TTG antibodies, 18 of the 19 were positive for both EMA-ELISA and TTG antibodies. A significant correlation was found between EMA-ELISA and TTG antibody titers (r = 0.74, P < 0.001). CONCLUSIONS: Our study demonstrates that EMA-ELISA is comparable to TTG antibodies in the diagnosis of CD, and supports the use of EMA-ELISA as a serologic marker for this disease.

Autoantibodies↗