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Leucocyte adhesion deficiency (LAD) is a rare, innate autosomal recessive immunodeficiency with three subtypes. Twenty-nine patients with LADs were diagnosed and treated in Israeli Medical Centers and in the Palestinian Authority. We discuss the phenotypic, genotypic and biochemical features of LAD-I, LAD-II and LAD-III diagnosed during the neonatal period and early infancy in 18, 6 and 5 patients, respectively. Consanguinity was frequent. Common features were severe infections of variable aetiology, excessive leukocytosis and delayed umbilical cord detachment. In LAD-I, the integrin CD18 expression varied from negligible to normal. However, CD11a expression was negligible in all tested patients, suggesting both CD11a and CD18 should be used to assess this subtype. LAD-II patients showed distinctive facial features, physical malformations, short stature and developmental delay. These patients show defective expression of SLeX (CD15a) on cell surface glycoproteins and lack of H antigen on erythroid cell surfaces resulting in Bombay blood group (hh). LAD-III showed intact but inactive β2 integrins associated with severe infections and significant bleeding disorders caused by defective platelet aggregation and thrombocytopenia. We report four patients with two new unpublished mutations: two LAD-I patients with c.1099delG in ITGB2 and two LAD-III patients with c.1069C>T in FERMT3. LAD-I patients harbouring the c.119_128 deletion in ITGB2 seemed to have better outcomes as compared to other LAD-I patients. Eight patients with LAD-I and -III underwent successful haematopoietic stem cell transplantation. Cumulative survival was 75%, 50% and 40% for LAD-I, LAD-II and LAD-III, with a median follow-up of 4 (0.08-19), 3.25 (1-32) and 6 (0.08-8) years, respectively. Prenatal diagnosis is recommended in families with LAD syndromes.

BackgroundMutations in the NCF1 gene that encodes p47phox, a subunit of the NADPH oxidase complex, cause chronic granulomatous disease (CGD). In Kavkazi Jews, a c.579G>A (p.Trp193Ter) mutation in NCF1 is frequently found, leading to CGD. The same mutation is found in about 1% of Ashkenazi Jews, although Ashkenazi CGD patients with this mutation have never been described.MethodsWe used Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), gene scan analysis and Ion Torrent Next Generation Sequencing for genetic analysis, and measured NADPH oxidase activity and p47phox expression.ResultsIn an Ashkenazi couple expecting a baby, both parents were found to be heterozygotes for this mutation, as was the fetus. However, segregation analysis in the extended family was consistent with the fetus inheriting both carrier alleles from the parents. MLPA indicated four complete NCF1 genes in the fetus and three in each parent. Gene sequencing confirmed these results. Analysis of fetal leucocytes obtained by cordocentesis revealed substantial oxidase activity with three different assays, which was confirmed after birth. In six additional Ashkenazi carriers of the NCF1 c.579G>A mutation, we found five individuals with three complete NCF1 genes of which one was mutated (like the parents), and one individual with in addition a fusion gene of NCF1 with a pseudogene.ConclusionThese results point to the existence of a ‘false-carrier’ state in Ashkenazi Jews and have wide implications regarding pre-pregnancy screening in this and other population groups.

Chronic granulomatous disease (CGD) is a rare congenital immune deficiency caused by mutations in any of the five genes encoding NADPH oxidase subunits. One of these genes is NCF1, encoding the p47(phox) protein. A group of 39 patients, 14 of whom are of Kavkazi Jewish descent, was investigated for a founder effect for the mutation c.579G>A (p.Trp193Ter) in NCF1. We analyzed various genetic markers in the NCF1 region, including two single nucleotide polymorphisms (SNPs) in NCF1 and two short tandem repeats (STRs) located near NCF1. Most patients were homozygous for the c.579G>A mutation, but three patients were hemizygotes, with a deletion of NCF1 on the other allele, and three patients were compound heterozygotes with another mutation in NCF1. All Kavkazi Jewish patients had a c.295G_c.345T SNP combination in NCF1 and shared a common number of repeats in STR3. In addition, 90% of the Kavkazi Jewish patients shared a common number of repeats in STR1. This uniformity indicates that the c.579G>A mutation in NCF1 was introduced some 1200-2300 years ago in the Kavkazi Jewish population. Variation amongst the other investigated populations from the Middle East indicates that this mutation exists in these non-Kavkazi populations already for more than 5000 years.

Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47phox deficiency. Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47phox by immunoblotting and molecular confirmation by DNA sequence analysis. Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47phox deficiency. Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.

Autosomal dominant Hyper IgE syndrome (AD-HIES) is a rare and complex primary immunodeficiency that affects multiple systems. Mutations in signal transducer and activator of transcription 3 (STAT3) gene cause AD-HIES. These mutations have a dominant-negative effect and the presence of such mutations is associated with a clinical phenotype. We aim to describe genetic and clinical characteristics of patients with AD-HIES in our clinic and to highlight the variability of clinical patterns in the same family. We describe six patients, four individuals of the same family and two unrelated patients. All patients were given a clinical score based on disease phenotype according to the National Institute of Health (NIH) score. Mutation analysis of STAT3 was done by PCR amplification of all coding exons followed by bidirectional sequencing using the BigDye kit v1.1 and an ABI3700 genetic analyzer (Applied Biosystems). All six patients had DNA binding region point mutations: a proband and his three children with p.Phe384Leu mutation, a patient with p.Arg382Trp substitution and a patient with p.Arg382Gln mutation. All of these mutations were previously reported. Patients differed in infectious, immunologic and somatic features. We observed an extreme variability in disease phenotype within the reported family with one genetically affected patient displaying an ‘unaffected’ phenotype. Although the genetic cause of AD-HIES is known, more studies are required to better understand the possible additional factors that may affect disease expressivity within families and the clinical diversity of the disease.

Chronic granulomatous disease (CGD) is an innate immunodeficiency with a genetic defect of the nicotinamide adenosine dinucleotide phosphate, reduced, oxidase components. This leads to decreased reactive oxygen species (ROS) production, which renders patients susceptible to life-threatening infections. Over the course of 30 years, we diagnosed CGD in 84 patients from 61 families using functional, molecular, and genetic studies. The incidence of CGD in Israel is 1.05 per 100,000 live-births in the Jewish population and 1.49 in the Israeli Arab population. We diagnosed 52 patients (62%) with autosomal recessive inheritance (AR-CGD) and 32 (38%) with X-linked recessive inheritance (XLR-CGD). Consanguinity was detected in 64% of AR-CGD families (14% in Jews and 50% in Israeli Arabs). We found 36 different mutations (23 in XLR-CGD and 13 in AR-CGD patients), 15 of which were new. The clinical spectrum of CGD varied from mild to severe disease in both XLR and AR forms, although the AR subtype is generally milder. Further, residual ROS production correlated with milder clinical expression, better prognosis and improved overall survival. Patients with recurrent pyogenic infections developed fibrosis and hyperinflammatory states with granuloma formation. The management of CGD has progressed substantially in recent years, evolving from a fatal disease of early childhood to one of long-term survival. Our present cohort displays an encouraging 81% overall long term survival. Early hematopoietic stem cell transplantation is advisable before tissue damage is irreversible. Successful transplantation was performed in 18/21 patients. Therapeutic gene modification could become an alternative cure for CGD. Am. J. Hematol. 92:28-36, 2017. © 2016 Wiley Periodicals, Inc.

Background There is a paucity of data on the relationship between demographic characteristics, specific clinical manifestations, and neutrophil dysfunction, guiding physicians to decide which clinical signs and symptoms are a code for an underlying phagocytic disorder. Methods The data over a 21-year period of all adult and pediatric patients referred to our Laboratory for Leukocyte Functions with recurrent pyogenic infections were analyzed. Neutrophil function studies included chemotaxis, superoxide production (SOP), bactericidal activity (BA), and specific studies in case of suspected primary phagocytic disorder (PPD). Results Neutrophil dysfunction was found in 33.6% of 998 patients; chemotaxis in 16.6%, SOP in 6%, and BA in 24.5%. The younger the patient and the more organ systems involved, the greater the probability of finding phagocytic impairment. Impaired chemotaxis correlated with recurrent aphthous stomatitis, infections associated with elevated IgE, and purulent upper respiratory tract infections. Impaired SOP and BA correlated with deep-seated abscesses, recurrent lymphadenitis, sepsis, and bone and joint and central nervous system infections. PPDs were identified in 5.7%, chronic granulomatous disease in 4.8%, neutrophil glucose-6-phosphate dehydrogenase deficiency in 0.3%, leukocyte adhesion deficiency type 1 in 0.4%, and myeloperoxidase deficiency in 0.2%. Phagocytic evaluation contributed to the diagnosis of hyperimmunoglobulin-E syndrome (n=21) and Chediak-Higashi syndrome (n=3). Conclusions PPDs are identified in 5.7% of patients with recurrent pyogenic infections; in the remainder, phagocytic dysfunction may be related to deleterious effects of persistent infection, drug consumption, or disorders not yet established

Chronic granulomatous disease (CGD) is an immune deficiency syndrome caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the enzyme that generates reactive oxygen species (ROS) in phagocytizing leukocytes. This study evaluates the NADPH oxidase capacity in two X-linked CGD patients with mutations in gp91(phox) that alter the regions in this membrane-bound NADPH oxidase component involved in docking of the cytosolic component p47(phox). Hydrogen peroxide and superoxide generation, bactericidal activity, and NADPH oxidase protein expression by the patients' neutrophils were measured, and genetic analysis was performed. We report two patients, each with a novel missense mutation in CYBB, the gene that encodes gp91(phox). Surprisingly, neutrophils from these patients showed total absence of superoxide production, although they retained 13-30% of the hydrogen peroxide production capability. We speculate that this is due to direct electron transfer from flavin adenine dinucleotide (FAD) in gp91(phox) to oxygen, leading to inefficient hydrogen peroxide formation instead of efficient superoxide production. X-linked CGD patients with mutations that alter the gp91(phox) protein in regions involved in docking of the cytosolic NADPH oxidase component p47(phox) may have higher than expected hydrogen peroxide generation capability

Purpose: Intense exercise bouts are associated with a reduction of immune function and increased susceptibility to infections. Neutrophils act as a first line of defense to eliminate infectious agents and are also involved in muscle tissue inflammatory response to exercise. Intensive exercise suppresses several neutrophil functions including chemotaxis. The study investigates the pathophysiological mechanisms of impaired chemotaxis after submaximal aerobic exercise. Methods: Twenty-three healthy physically active adult males were tested before and 24 h after 30 min of treadmill running at 75% V[spacing dot above]O2max. N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophil migration, polarization, adherence, expression of adhesion molecules (CD11b/CD18), and chemotactic receptor (C5aR) were assessed preexercise and postexercise. Results: Neutrophil chemotaxis and polarization were found to be impaired 24 h postexercise. Adherence was impaired 24 h postexercise as well, but the expression of the adhesion molecule CD11b/CD18 was not affected. Further, the availability of the C5aR was found to be unaffected 24 h postaerobic exercise. Conclusions: The pathophysiological mechanism of the impaired chemotaxis is likely related to the impaired postexercise neutrophil adherence and polarization but not to changes in the chemotactic receptor availability

Obesity has become the most common pediatric chronic disease in the modern era. Recent data suggests that unlike obese adults, obese children and adolescents may have decreased bone strength. It was the objective to prospectively examine the short term effects of a 3 month combined dietary-physical activity intervention on anthropometric measures, body composition, fitness and bone strength in obese children. Twelve obese subjects completed the 3 m intervention and were compared to 12 obese age and gender matched controls. Bone strength was measured using quantitative ultrasound measurements of bone speed of sound (SOS). There were significant differences in changes of body weight (0.01 +/- 0.7 vs. 2.3 +/- 0.6 kg, p = 0.033), BMI percentiles (- 2.8 +/- 1.1 vs. - 0.2 +/- 0.2 %, p = 0.037), body fat percent (by skinfolds, - 1.5 +/- 0.8 vs. 0.7 +/- 0.5 %, p = 0.035), and endurance time (170 +/- 42 vs. 50 +/- 27 s, p = 0.045) in the intervention vs. control subjects, respectively. In addition, we found a significant difference in the change of bone SOS between the intervention and control group subjects (21.5 +/- 21.6 vs. - 87.0 +/- 37 m/s, p = 0.023). During the critical period of bone development of childhood and adolescence, a combined dietary-physical activity intervention leads to increased bone strength in obese children. These results highlight the importance of multi-disciplinary programs for the treatment of childhood obesity and its complications.

To examine the prevalence of abnormal thyroid function tests among obese children and adolescents, and to study the effect of thyroid hormone supplementation on body weight, linear growth and lipid profiles in these children.Thyroid function tests and lipid profiles were measured in 196 obese children and adolescents. Thyroid auto-antibodies were measured in children with hyperthyrotropinemia (elevated thyroid stimulating hormone (TSH) and normal free thyroxine-FT4). All children with hyperthyrotropinemia participated in a combined dietary-behavioral-physical activity weight management intervention. Fifteen of the obese children with hyperthyrotropinemia were also treated with thyroid hormone substitution for 6 months and were compared to non-treated subjects (n = 26).Forty-one obese children had hyperthyrotropinemia (20.9%). Positive thyroid auto-antibodies were only found in 19.5% of these children. Treatment had no significant effect on body weight, linear growth and lipid profile, except for causing a greater decrease in triglyceride levels. TSH levels returned to normal ranges in the majority of children with hyperthyrotropinemia who participated in the combined intervention, irrespective of thyroxine treatment.Hyperthyrotropinemia is relatively common in obese children, but autoimmune thyroid disease accounts for a minority of the cases. TSH levels returned to normal in the majority of patients even without thyroid hormone administration. No beneficial effects on body weight, body mass index, linear growth and body lipids were found in treated subjects, suggesting that thyroid substitution is not necessary in most cases.

OBJECTIVES: To study the epidemiology and risk factors for unintentional exposure to poisoning among the Jewish and the Arab population in the Sharon area in Israel. METHODS: We prospectively evaluated visits to the pediatric emergency department because of unintentional poisoning exposure, at the Meir General Hospital. We collected demographic data, substance exposure data, and the clinical outcome of the poisoning. RESULTS: During the 5 years of the study, 502 children were evaluated for unintentional poisoning, 84% Jewish and 16% Arabs; 88.5% occurred in children younger than 5 years, with a peak incidence at the age of 2 years (39.5%). Medications including hormones, vitamins, and antibiotics were the most common cause of exposure. Most children (95%) had no symptoms or abnormal findings on physical examination (84%), and most (85%) were discharged after several hours of observation. However, children of Arab origin presented with severe clinical manifestations because of a high rate of pesticide poisoning. There was 1 death from organic phosphate poisoning. CONCLUSION: Exposure to poisoning is commonly encountered in children. Pesticides exposure is more common in the Arab community and is usually associated with more severe clinical manifestations. Educational preventive programs are mandatory.

Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92] → GGT), predicting Tyr30Arg31 → stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow.

We report for the first time a child with chronic granulomatous disease (CGD) who developed acute lymphoblastic leukemia (ALL). The diagnosis of CGD was made at the age of 4 months, by studies of his neutrophil functions. The superoxide production of the cells was negligible, as was the bactericidal activity. He was found to have a deficiency of the gp91(phox) subunit of the leukocyte NADPH oxidase, with the X-linked inheritance of the disease. DNA analysis revealed a C nucleotide insertion between C1028 and T1029. This insertion has not been described before and causes a frameshift and a premature stop codon at amino-acid position 347. The mother was found to be a carrier of this mutation. At the age of 16 months, the patient developed T-cell ALL. He was treated for 2 years, and today, 10 years since the diagnosis, he is disease-free. During the course of ALL and later, he suffered from recurrent severe pyogenic infections, but careful detection of the etiological agent and promptly instituted specific treatment resulted in his complete recovery. Although primary immune deficiencies have been reported to have an increased tendency to develop malignancies, until now there have been no reports of CGD patients with ALL.

Defective neutrophil function in schizophrenic patients has recently been reported. There are several lines of evidence to support the contribution of oxygen free radicals in schizophrenia, including increased lipid peroxidation, fatty acids and alterations in blood levels of anti-oxidant enzymes. Eighteen schizophrenic patients (DSM-IV) and 15 healthy controls were studied. Neutrophil chemotaxis, superoxide production and bactericidal activity were investigated. A statistically significant increase of superoxide anion release was found in schizophrenic patients compared with controls (mean+/-S.E.M., patients: 6.89+/-0.30 nmol O2-/10(6) cells/min, controls: 5.13+/-0.55 nmol O2-/10(6) cells/min). Moreover, a significant positive correlation between superoxide production and negative symptoms as assessed by the Positive and Negative Syndrome Scale was demonstrated. No differences were detected in chemotaxis and phagocytosis between schizophrenic patients and healthy controls. The present findings of a positive correlation between superoxide generation and negative symptoms in schizophrenic patients support the hypothesis that superoxide anion may participate in the pathogenesis of schizophrenia, as an excess of free radicals could contribute to the deterioration phase of the disease. Further studies are required to establish the role of oxidative stress in the ethiopathogenesis of schizophrenia.

Objective Velocardiofacial syndrome (VCFS) is the most common multiple anomaly disorder associated with palatal clefting. Cytogenetic hemizygous deletion of 22q11 region is found in 80% of patients. The frequency of 22q11 deletion in patients presenting with isolated palatal anomalies has not been fully assessed. Our objective was to determine the frequency of the deletion in patients with isolated palatal anomalies. Design Patients were referred because of velopharyngeal insufficiency because of isolated congenital palatal anomalies. Diagnosis of palatal anomalies was confirmed by videonasopharyngoscopy, multiview videofluoroscopy and cephalometry. Other clinical findings suggestive of VCFS were sought, and subjects with these characteristics were excluded from the study. Peripheral blood samples from all patients were analyzed cytogenetically utilizing fluorescent in situ hybridization for the 22q11 region. Results Thirty-eight patients aged 3 to 31 years were included in the study. Nine had cleft palate, 7 cleft lip and palate, 10 overt and 11 occult submucous cleft palate, and 1 had a deep nasopharynx. No deletion of 22q11 region was detected in any of the evaluated patients. Conclusions A routine screening for the 22q11 deletion in older children and adults presenting with an isolated palatal anomaly may not be required. Because other signs related to VCFS such as facial dysmorphism and behavioral or psychiatric disorders may evolve at an older age, young patients should be followed up and reevaluated for additional relevant symptoms that may lead to deletion evaluation. In light of the fact that the current literature is inconsistent, the relative small size of this study and the significant consequences of missed 22q11.2 deletion, more information is needed before definitive recommendations can be made.

Leukocyte adhesion deficiency type III (LADIII) is an autosomal recessive disorder that presents with a severe leukocyte adhesion defect and a Glanzmann-type thrombocytopathy. Hematopoietic stem cell transplantation (HSCT)--the only definitive treatment for LADIII--appears to have a high rate of complications. In this study, we describe a new group of patients with LADIII, highlighting further clinical and immunologic aspects of this disease, and reevaluating the effectiveness of HSCT for its treatment. The patients had clinical and laboratory findings consistent with LADIII. Molecular analysis confirmed the presence of a mutation in the kindlin-3 gene. HSCT was carried out in 3 patients and was successful in 2. The diagnosis of LADIII should be considered in all patients who present with recurrent infections and a bleeding diathesis, regardless of the leukocyte count. LADIII is a primary immune deficiency, which can be successfully corrected by bone marrow transplantation if applied early in the course of the disease using appropriate conditioning.

We measured bone speed of sound in premature infants by quantitative ultrasound. A total of 44 neonates participated in the study including 29 premature infants (median birth weight 1264 g, range 578–2420 g; median gestational age 31 weeks, range 24–36 weeks) and 15 full-term infants (median birth weight 3360 g, range 2700–3730 g; median gestational age 40 weeks, range 37–41 weeks). The left tibial speed of sound (SOS) was measured by quantitative ultrasound. Bone SOS was successfully measured in all infants. We found a significant correlation between tibial SOS and gestational age (r=0.78, P

Object. The aim of this prospective study was to evaluate the phagocytic, humoral, and cellular arms of the immune system in comatose patients shortly after severe brain injury and to compare the findings with those reported earlier in patients in a persistent vegetative state. The study was conducted in intensive care units and immunology laboratories of university-affiliated hospitals in central Israel. Methods. The study group consisted of 14 men aged 16 to 65 years who were comatose as a result of acute brain injury due to mechanical trauma. All were studied within 72 hours of injury. Brain damage was severe in all cases (Glasgow Coma Scale score < 8). Healthy age- and sex-matched volunteers served as simultaneous controls. Infections arose in nine (75%) of the 12 patients in whom data were available; the cumulative mortality rate was 38% (five of 13 patients in whom outcome data were available). Every patient exhibited one or more defects in at least one arm of the immune system. Significant deficiencies were noted in neutrophil superoxide release, immunoglobulin (Ig)G, IgG1, IgM, C1q, C2, properdin, alternate C pathway, T cells, T helper cells, T suppressor cells, and natural killer cells. In an earlier series of patients examined by the authors months after the primary insult, these impairments were absent in most of the patients in the vegetative state. Conclusions. Significant deficiencies of the immune system, particularly the cellular arm, are precipitated by severe brain injury within 72 hours of the event. These impairments probably play a role in the high rate of complicating infections and multiple organ failure. Together with earlier findings, the results of this study indicate that if brain-injured patients survive these hazards, their immune system will eventually recover.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by impaired microbial killing and susceptibility to bacterial and fungal infections. Cure of the disease can be achieved by stem cell transplantation when performed early in its course, and before severe infections have developed. Invasive aspergillosis constitutes a very high risk for transplantation. We report a 4-year-old boy with X-linked CGD who underwent successful HLA-identical peripheral blood stem cell (PBSC) transplantation during invasive pulmonary aspergillosis and osteomyelitis of the left fourth rib, which was unresponsive to antifungal treatment. During the 2 months prior to the transplant he received G-CSF-mobilized granulocyte transfusions (GTX) from unrelated donors three times a week in addition to the antifungal treatment. This resulted in clinical improvement in his respiratory status. He also received GTX during the aplastic period after the conditioning regimen, until he had engrafted. Post-transplant superoxide generation test revealed that neutrophil function was within normal range. One year post transplant the CT scan showed almost complete clearance of the pulmonary infiltrates and a marked improvement in the osteomyelitic process. Based on other reports and our own experience, GTX can serve as important treatment in patients with CGD who have failed conventional anti-fungal treatment and for whom stem cell transplantation is the only chance for cure.

Objectives—Recent studies have indicated reduced immunity in trained athletes. Aim—To assess the effects of aerobic and anaerobic exercise on the phagocytic process in 18–26 year old trained female judoka (n = 8) and untrained controls (n = 7). Methods—Each subject participated randomly in two different testing sessions (aerobic, 20 minutes of treadmill running at 70–80% of maximal heart rate; anaerobic, Wingate anaerobic test). Venous blood samples were drawn before, immediately after, and 24 hours after each session. Results—There were no significant differences in basal values of net chemotaxis (chemotaxis - random migration), bactericidal activity, and superoxide anion release between the judoka and the untrained women. There was a significant decrease in net chemotaxis 24 hours after the aerobic exercise in both the judoka (from 64 (19) to 39 (13) cells/field, p

Aim: To assess the influence on blood pressure in schoolchildren, of elevated sodium (Na+) and nitrate (NO–3) levels in the drinking water. Methods: The blood pressure was recorded in three groups of age- and weight-matched schoolchildren (fourth and fifth graders) ingesting differing Na+ and NO–3 concentrations with their drinking water. Group 1 (n = 452) imbibed high-Na+, high-NO–3 water (196 and 49 mg/l, respectively); group 2 (n = 418) consumed low-Na+, high-NO–3 water (25 and 49 mg/l, respectively) and group 3 (n = 86) drank low-Na+, low-NO–3 water (35 and 25 mg/l, respectively). The chloride (Cl–) concentrations varied in parallel to those of Na+. Results: Systolic blood pressure (SBP) and mean arterial pressure (MAP) were significantly increased in group 1 versus groups 2 and 3 (115.6 ± 12.2 and 86.4 ± 9.6 mm Hg vs. 111.1 ± 11.6 and 83 ± 8.3 and 107 ± 8.8 and 81 ± 7.2 mm Hg, respectively, p < 0.05). The SBP in group 2 was also significantly higher than in group 3 (111.1 ± 11.6 vs. 107 ± 8.8 mm Hg; p < 0.05). Conclusions: Elevated Na+ (and possibly Cl–) in combination with high NO–3 concentrations in drinking water leads to an increase of SBP and MAP in fourth and fifth graders. The effects of Na+ (and/or Cl–) and NO–3 on SBP and MAP appear to be additive, yet independent of each other.

The myeloproliferative disorders (MPD) are clonal diseases that originate from a transformed stem cell and involve all myeloid lineage. The affected cells have both proliferative and functional impairment. Therefore, we evaluated and compared neutrophil function in 31 patients with polycythemia vera (PV), idiopathic myelofibrosis (MF), chronic myeloid leukemia (CML), and essential thrombocytosis (ET). Neutrophil chemotaxis, random migration, bactericidal activity and superoxide anion release in these patients were simultaneously compared to those of 31 healthy controls. In this study, chemotactic activity was significantly impaired in patients with PV and CML as compared to controls (M+/-SE: 42 +/- 6 vs. 69+/- 5 cells/field; p0.005 and 47+/-7 vs. 68+/- 5; p0.05, respectively). The assessment of the bactericidal activity of neutrophils showed no impairment in most of the patients. In the CML group, the serum had a very strong "lytic" effect on bacteria, possibly due to the high levels of serum lysozyme (22 +/- 2 microgram/ml). The superoxide anion release was found to be normal in most of the patients. Nevertheless, in 25% of PV patients the superoxide production was impaired (less than 60% of the simultaneous controls). In ET most patients had normal neutrophil function. Regarding the effect of treatment, neutrophil chemotactic activity was found to be significantly reduced in the hydrea-treated patients, as compared to the non- treated patients (p0.001) or healthy controls (0.0001). We conclude that disturbances in neutrophil function are present in patients with various MPDs, except ET. This probably reflects abnormal maturation of ancessors of the damaged stem cells. Nevertheless, we should keep in mind that therapy itself could affect neutrophil functions. This matter should be studied more extensively. Although infections are not common in MPD disorders, they occasionally occur. It is possible that impairment in the phagocytic function contribute to the development of infections in patients with myeloproliferative disorders.

The aim of this study was to assess sleep and pulmonary function in asthmatic and control children. Forty children with well-controlled, stable asthma, and 34 controls (age range: 8.2 to 15.4 years) were monitored with wrist actigraphs and peak-flow meters for 3 consecutive days. In addition, asthma severity was assessed by subjective parental and self-rating scale and symptom checklist. Asthmatic children had poorer sleep quality in comparison to their controls, as manifested in lower percentages of quiet sleep (p < .05) and increased activity level during sleep (p < .05). As expected, asthmatic children had reduced morning peak expiratory flow measures (p < .01) and a higher evening-to-morning drop in peak expiratory flow (p < .005). Peak-flow measures were significantly correlated with subjective and objective sleep measures. In the asthmatic group, sleep measures were also correlated with subjective asthma severity indices and symptom checklists. We conclude that poorer sleep is associated with reduced pulmonary function. The reduced sleep quality, coupled with subjective reports of increased fatigue and reduced alertness found in asthmatic children, suggest that these children are at risk for developing neurobehavioral deficits associated with chronic sleep loss.

Brucellosis has become a major medical problem in Israel particularly in the Muslim Arab population.Eighty-eight children with acute brucellosis are described. Sixty-seven were studied retrospectively during 1987 through 1988, and 21 children were studied prospectively during 1989 through 1992. Epidemiologic, clinical and laboratory features were evaluated, and the outcome of 4 antimicrobial regimens are compared.Although the clinical manifestation varied, the classical triad of fever (91%), arthralgia or arthritis (83%) and hepato- and/or splenomegaly (63%) characterized most patients. Sixty-one percent of the children had elevated liver enzymes. Brucella melitensis was isolated from 61% of blood cultures. The relapse rate in patients who were treated with monotherapy (doxycycline) was 43% compared with 14% with regimens of combined therapy with rifampin and doxycycline, streptomycin and doxycycline or rifampin and trimethoprim-sulfamethoxazole (P0.049). Eleven children (33%) who were treated for 3 weeks had relapse compared with 1 patient (3.5%) treated for 4 weeks or longer. The total relapse or reinfection rate was 20%. All patients with relapse recovered after a second course of antibiotic therapy. During the 2 years of follow-up one child progressed to chronic osteomyelitis.Combination therapy and extending treatment for 4 weeks or longer gave significantly better results than monotherapy or shorter courses of therapy and resulted in fewer relapses.

The study objectives were to determine the impact of a nationwide educational campaign on the incidence of foreign body aspiration (FBA) in Israeli children. Impressed by the alarming number of FBAs, we conducted an educational campaign through the media during 1982-1983. The campaign included television and radio broadcasts, newspaper articles and interviews, and medical educational programmes in community paediatric care centres. Questionnaires were sent to all Departments of Paediatrics in Israel. Results showed a reduction in the incidence of FBA by 35% in 1983 as compared to 1981. Re-evaluation studies conducted in 1992 showed no further reduction of FBA. CONCLUSION. Continuous and extensive educational programmes should be undertaken by the health authorities if FBA is to be prevented. Furthermore, it is important to legislate mandatory labelling of seed and nut containers with the warning that the intake of seeds is dangerous to children under 5 years of age.

Two cases of atypical Kawasaki disease (KD) manifested as persistent lobar lung consolidation, prolonged fever, and active inflammatory laboratory markers unresponsive to antibiotic treatment are reported. One of the children developed a giant coronary aneurysm. Atypical KD should be considered in the differential diagnosis of young children with prolonged fever and lobar consolidation unresponsive to antibiotics.

The treatment of an acute asthma attack usually includes bronchodilators and often steroids. We studied 70 children who were randomly assigned to receive either single dose steroids (oral prednisone: 20-40 mg) or placebo on a double blind basis. The time course of the observation was 72 h. We demonstrate that a single dose of steroids, given orally in paediatric community clinics during an acute mild to moderate asthma attack, significantly improves the patient's course; deterioration was prevented, symptoms were relieved faster, and hospitalization was not required. We encourage paediatricians in the ambulatory clinics to follow this treatment modality and to give, in addition to other conventional therapy, a single oral dose of steroids early in the asthma attack, in order to relieve and shorten the child's distress.

We describe three Israeli children with fatal spotted fever. Clinical disease was characterized by irreversible shock, encephalopathy, renal failure, bleeding tendency, and death within 24 hours of admission. None of the patients had a history of tick bite, and no tache noire was noted. One child presented without rash, and the other two did not have antibodies to spotted-fever-group rickettsiae. The disease was confirmed by isolation of Rickettsia conorii from the patients' blood and tissues in cell cultures or from susceptible laboratory animals inoculated with human specimens. The present cases demonstrate the existence of a severe form of Israeli spotted fever in this population that resembles Rocky Mountain spotted fever. Because Israeli spotted fever may follow a quick, unpredictable, rapidly fatal clinical course, specific antimicrobial therapy should be promptly administered whenever the diagnosis is suspected.

Post-comatose unawareness (PCU) is one of the possible outcomes of severe brain injury. Patients with severe brain injury have an increased susceptibility to severe nosocomial infections for multifactorial reasons, including immune suppression at different levels. We studied different immunological aspects in 11 PCU patients. Impaired humoral immunity was found in 27% of them. Two patients had decreased haemolytic activity of the classical complement pathway, associated with decreased levels of the components C1q, C1r and C4. Another patient had very low levels of IgG2 and IgG4. The neutrophil killing activity was impaired in these three patients, but was completely restored with the addition of a heterologous serum, suggesting a humoral defect. Neutrophils showed normal chemotaxis and random migration, and the superoxide anion release by neutrophils was also found to be normal. Understanding the immunological events in PCU patients contributes to a better and more intensive therapeutic approach, which might accelerate the rehabilitation of these patients.

BackgroundLeukocyte adhesion deficiency 1 (LAD1) is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2) gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.g., gentamicin) were reported to partially correct the premature protein termination, by induction of readthrough mechanism.Methodology/principal findingsGenetic analysis was performed on 2 LAD1 patients. Expression, functional and immunofluorescence assays of CD18 in the patients were used to determine the in-vivo and in-vitro effects of gentamicin-induced readthrough. A theoretical modeling of the corrected CD18 protein was developed to predict the protein function.ResultsWe found a novel premature termination codon, C562T (R188X), in exon 6 of the CD18 gene that caused a severe LAD1 phenotype in two unrelated Palestinian children. In-vivo studies on these patients' cells after gentamicin treatment showed abnormal adhesion and chemotactic functions, while in-vitro studies showed mislocalization of the corrected protein to the cytoplasm and not to the cell surface. A theoretical modeling of the corrected CD18 protein suggested that the replacement of the wild type arginine by gentamicin induced tryptophan at the position of the nonsense mutation, although enabled the expression of the entire CD18 protein, this was not sufficient to stabilize the CD18/11 heterodimer at the cell surface.ConclusionA novel nonsense mutation in the CD18 gene causing a complete absence of CD18 protein and severe LAD1 clinical phenotype is reported. Both in vivo and in vitro treatments with gentamicin resulted in the expression of a corrected full-length dysfunctional or mislocalized CD18 protein. However, while the use of gentamicin increased the expression of CD18, it did not improve leukocyte adhesion and chemotaxis. Moreover, the integrity of the CD18/CD11 complex at the cell surface was impaired, due to abnormal CD18 protein and possibly lack of CD11a expression.

The current medical management of children with chronic suppurative otitis media without cholesteatoma unresponsive to local treatment and oral antibiotics is intravenous antibiotic therapy in the hospital setting. We studied the efficacy and toxicity of oral ciprofloxacin in chronic suppurative otitis media. Twenty-one children received oral ciprofloxacin, 30 mg/kg/day. Ear discharge was positive for bacteria resistant to other oral medications and susceptible to the quinolones. The mean duration of treatment was 16.7 days. In 18 children suppuration ceased and 3 failed their first course. During a mean follow-up of 15.4 months, 6 children remained free of ear, nose and throat problems. Otorrhea recurred in 12 children. Ear cultures were positive for organisms susceptible to amoxicillin in 5 of them. In 7 cases Pseudomonas aeruginosa was again isolated from otorrhea. Repeated antibiotic therapy was advocated only in 3 (2 responded to ciprofloxacin; 1 failed ciprofloxacin and was cured by ceftazidime). Adverse clinical effects were not observed. Transient neutropenia was observed in 1 child. There was no change in the height percentile. The results of this study show that children with chronic suppurative otitis media without cholesteatoma can be effectively treated with oral ciprofloxacin. This novel approach may prevent hospitalization.

International audience; CGD is an immunodeficiency caused by deletions or mutations in genes that encode subunits of the leukocyte NADPH oxidase complex. Normally, assembly of the NADPH oxidase complex in phagosomes of certain phagocytic cells leads to a "respiratory burst", essential for the clearance of phagocytosed micro-organisms. CGD patients lack this mechanism, which leads to life-threatening infections and granuloma formation. However, a clear picture of the clinical course of CGD is hampered by its low prevalence (approximately 1:250,000). Therefore, extensive clinical data from 429 European patients were collected and analyzed. Of these patients 351 were males and 78 were females. X-linked (XL) CGD (gp91(phox) deficient) accounted for 67% of the cases, autosomal recessive (AR) inheritance for 33%. AR-CGD was diagnosed later in life, and the mean survival time was significantly better in AR patients (49.6 years) than in XL CGD (37.8 years), suggesting a milder disease course in AR patients. The disease manifested itself most frequently in the lungs (66% of patients), skin (53%), lymph nodes (50%), gastrointestinal tract (48%) and liver (32%). The most frequently cultured micro-organisms per episode were Staphylococcus aureus (30%), Aspergillus spp. (26%), and Salmonella spp. (16%). Surprisingly, Pseudomonas spp. (2%) and Burkholderia cepacia (

Chronic granulomatous disease (CGD) is an innate immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. In the course of 21 years, 38 Israeli CGD patients were diagnosed with 17 gene mutations, seven of which were new. Clinical, functional, and molecular studies were accomplished. Although X-linked recessive (XLR)-CGD is worldwide the most common genotype of the disease (~70%), in our study only 11 patients (29%) suffered from XLR-CGD. In Israel, the higher incidence of the autosomal recessive (AR) form of CGD (63%) may be related to consanguineous marriages. In three patients (8%), all four proteins of the NADPH oxidase were present. Severe clinical expression was found both in the XLR and AR forms, but in general a milder disease was evident in AR-CGD, particularly in patients with p47(phox) deficiency. Despite early and aggressive therapy, a mortality rate of 26% was noted. Given that bone-marrow transplantation was successful in five of seven patients, it is recommended to perform it as early as possible before tissue damage is irreversible.

Thrombocytosis is seen in association with many conditions, including infectious diseases. We studied thrombocytosis after severe bacterial infections, particularly pneumonia with empyema in children. A systematic survey of the phenomenon was conducted. Twenty-seven children admitted for pneumonia with empyema were studied. Thrombocytosis (platelet counts greater than 500 x 10(3)/microliters) was present in 92.5%. Platelet counts reached their maximum at 15.1 +/- 3.7 days (range, 7 to 25) and declined to normal after 3 weeks of illness. Compared with a healthy control group, significant thrombocytosis, but of lower incidence, was also noted in children with lobar pneumonia without pleural effusion, bacterial meningitis and osteomyelitis. Platelet functions were examined in seven of the children but no abnormalities were observed. Bone marrow aspiration of three children with pneumonia and empyema showed megakaryocytic hyperplasia. We found no correlation between thrombocytosis, neutrophilia, fever, the clinical course, complications, prognosis or treatment. Neither thromboembolic nor hemorrhagic phenomena were observed.

Bilateral choanal atresia is a rare but life-threatening disorder. Prompt diagnosis and emergency treatment are necessary. Various transnasal tools as well as other techniques have been tried in the past; they have all been associated with complications. The authors report a treatment of a newborn with a simple and previously unreported procedure for dealing with bilateral choanal atresia. As described, the use of a simple hand-powered drill and bit offers an approach which is straightforward and free of complications. Efficacy of this procedure is documented by a 6-year follow-up period.

The most common cause of recurring childhood musculoskeletal pain is termed growing pains (GP). We hypothesized that GP may represent a local overuse syndrome and therefore may be associated with decreased bone speed of sound (SOS) measured by quantitative ultrasound (US).We studied 39 children with GP. Bone SOS was measured by US in both mid-tibial and radius bones according to a validated protocol. Unpaired Student t test was used to compare patients and norms of healthy controls.Tibial SOS was significantly reduced in children with GP compared to controls (Z score -0.546 for boys and -0.891 for girls; p = 0.004, p0.001, respectively). Radius SOS was significantly reduced only in girls with GP (Z score -0.692, p = 0.006). No correlation was found between bone SOS and various demographic and clinical factors besides the child's ethnicity and body mass index.Bone SOS was significantly reduced in children with GP, especially in painful tibial regions. GP may represent a local overuse syndrome.

Objective: To assess the effects and identify factors associated with success of a combined, structured multidisciplinary weight management program in obese children and adolescents. Methods: Seventy-seven obese children (age 6-16 years) participated in a 12-month combined dietary-behavioral-exercise intervention. Thirty-seven (age and maturity comparable) obese children who did not participate in the structured program served as controls. Body weight, BMI, and BMI percentiles were measured at baseline, after 6 months, and at the end of the intervention. Results: The combined intervention was associated with a significant decrease in BMI (from 25.9 ′ 0.4 to 24.5 ′ 0.4 kg/m 2 , p

Hemoglobin Taybe is an unstable alpha-chain hemoglobin variant caused by a deletion of a threonine residue at codon 38 or 39 of the alpha-1 globin chain. We describe preterm infant triplets born with hydrops fetalis and anemia who were found by DNA analysis to be homozygous for hemoglobin Taybe. All three infants developed intrauterine hemolytic anemia, which subsequently led to hydrops fetalis. To the best of our knowledge, this is the first description of hydrops fetalis associated with this hemoglobinopathy. We suggest that hemoglobin Taybe be considered in the differential diagnosis of hydrops fetalis and that known affected fetuses be carefully followed both antenatally and postnatally.

To investigate whether children with recurrent musculoskeletal pain termed growing pains (GP) have lower pain thresholds than children without GP.We measured the pain threshold of 44 children with GP and 46 controls. Pain thresholds were measured by use of a Fisher type dolorimeter with pressure applied to areas associated with increased tenderness in fibromyalgia (FM), control points, and anterior tibia, the usual region of pain in children with GP. Unpaired Student's t test and chi-square tests were used to compare the pain threshold and number of tender points in patients and controls.The pain threshold in characteristic tender points of FM, control points, and anterior tibia in the children with GP was significantly lower in children with GP (3.5 +/- 0.6 kg/cm2 in GP versus 4.0 +/- 0.7 in controls, p0.001, 3.8 +/- 0.7 versus 4.4 +/- 0.8, p = 0.005; 5.1 +/- 1.1 versus 5.9 +/- 1.5, p = 0.004). Children with GP had a significantly greater number of tender points in response to an applied pressure of 4 kg/cm2.Children with GP have more tender points and lower pain thresholds than children without GP indicating that GP may represent a variant of a noninflammatory pain syndrome in younger children.

The role of the pediatric emergency department (ED) in the management of acute asthma was assessed by examining patterns of referrals, admissions, clinical patient evaluation, laboratory tests ordered, and treatment instituted. The functioning of the attending physicians with different degrees of seniority was also evaluated. One thousand thirty-six children with acute asthma (5.3% of all visits) were admitted to the ED during 1990. The mean age was 5.5 years, and the male to female ratio was 2.6:1. Fifty percent of the patients reported atopic disease in their immediate family, and upper respiratory tract infection preceding the attack was reported in 27% of patients. Significant differences were observed between Arab and Jewish patients: more Arab patients presented after physician referral (90 vs 33%) in morning hours (43 vs 26%), and after a longer duration of symptoms. Experienced physicians ordered fewer laboratory tests and treated the patients less aggressively than junior physicians. Patients treated by senior physicians stayed less time in the ED, and a smaller proportion of patients was hospitalized (4 vs 19%). Patients admitted by senior physicians had a longer period of hospitalization (4.7 vs 1.2 days). This study shows that ethnicity influenced the pattern of utilization of the ED and that the approach to care differed among junior and senior physicians.

The inflammatory process in torticollis involves the cervical muscles, nerves, and/or the vertebral synovia causing painful and abnormal head position. Most cases of acute acquired non-traumatic torticollis are of benign etiology, but some patients may suffer from a serious disease requiring thorough investigation and hospitalization.To describe the epidemiology, clinical features and the etiology of acute acquired non-traumatic torticollis in our center.A retrospective chart review of 45 hospitalized children in the Sapir Medical Center over a 10 year period.We studied 45 children; 23 girls and 22 boys. Their mean age was 6 years (range 6 months to 16 years). All patients reported marked neck pain as their main complaint. Local infection was the most frequent etiology, and 33 (73%) patients were hospitalized during the fall-winter season. Twenty six patients underwent x-ray imaging, and of these, ten (38%) had pathology. The main findings were some degree of atlanto-axial subluxation, and widening of the prevertebral space. Treatment included analgesic and antibiotics for suspected bacterial infections. Two patients required surgical drainage. Cervical neck traction was performed on 15 patients. Mean admission time was 4.1 days and was shorter in the pediatric department compared to the ENT and orthopedic departments.Careful clinical and radiological evaluation for the wide spectrum of clinical entities should be done. Local infections of the respiratory tract are the most common etiology. Conservative treatment usually leads to complete resolution in a short time.

BACKGROUND: In experimental animals, a reduction in renal mass leads to glomerulosclerosis of the residual parenchyma and eventual renal failure. In humans, however, data on the influence of nephrectomy or agenesis on future functional parameters and hypertension are as yet controversial. OBJECTIVE: To evaluate blood-pressure patterns in children with a solitary kidney as a result of either unilateral renal agenesis (URA) or uninephrectomy (UNX) and correlate them to the increase in size of the remaining kidney. METHODS: Twenty-eight children with a solitary kidney were divided into two groups: the URA group, with 18 subjects (13 male and five female, with a mean age of 9.6 +/- 3.9 years), and the UNX group, which contained 10 subjects (four male and six female, with a mean age of 14.0 +/- 2.7 years). The mean time since nephrectomy was 8.7 years. Each study group was assigned an age-, weight- and height-matched control group. In all subjects, ambulatory blood pressure monitoring was performed using the SpaceLabs model no. 90207. Daytime and night-time were defined as 0800-2200 h and 2200-0800 h, respectively. Urinalysis, serum creatinine and urea results were recorded for all the study group participants. The size of the remaining kidney was determined by ultrasound examination. The percentage increase in kidney size, as calculated from standard kidney-length-against-age nomograms was correlated to the percentage deviation from normal blood pressure values. RESULTS: The mean 24 h, daytime and night-time systolic blood pressure (SBP) readings were significantly higher in children in the URA group than in those in the corresponding control group (111.4 +/- 7.5 mmHg versus 106.9 +/- 6.7 mmHg, P < 0.004; 115.2 +/- 3.1 mmHg versus 110.7 +/- 3.4 mmHg, P < 0.004; and 105.2 +/- 2.6 mmHg versus 101.2 +/- 1.8 mmHg, P < 0.002, respectively). Daytime heart rate was found to be significantly reduced (84.4 +/- 5.2 versus 87.8 +/- 8.2 beats/min, P < 0.04). In the UNX group, 24 h mean, systolic and diastolic blood pressure (DBP), as well as heart rate, did not differ from control values. Daytime systolic and diastolic blood pressures were higher than those of the controls (119.8 +/- 4.0 mmHg versus 115.5 +/- 3.8 mmHg, P < 0.02; and 72.7 +/- 4.0 mmHg versus 70.0 +/- 11.0 mmHg, P < 0.02, respectively). Nocturnal dipping was present in all groups and was of equal magnitude in the corresponding control groups. The mean 24 h diastolic blood pressure load was significantly greater in URA patients than in controls (19.6 versus 10.8%, respectively, P < 0.01). In the UNX group, the blood pressure loads were similar to those of controls. The percentage increase in length of the remaining kidney was found to correlate positively with the percentage delta increase in both systolic and diastolic blood pressure. CONCLUSIONS: Compared with the age-, height- and weight-matched controls, the children with a solitary kidney caused by URA had an elevated mean 24 h SBP. In contrast, those with UNX had mean 24 h blood pressure values similar to those of their controls. A rise in SBP was, however, seen in both groups during the daytime hours. Thus, the presence of a solitary kidney, for whatever reason, may be pathogenetically linked to a raised blood pressure, and this linkage may be more pronounced in URA. The delta increase in size of the remaining kidney may serve as a prognostic indicator of blood pressure elevation.

We assessed the effect of a weight management programme on body weight, body mass index (BMI), and fitness in obese children and adolescents. The study was designed as a longitudinal, non-randomised, clinical experience of a 3 and 6 month combined dietary-behavioural-exercise intervention. A total of 177 obese children (age 6–16 years) participated in the 3 month programme, of whom 65 completed the 6 month intervention. A group of 25 age- and maturity-matched obese children who did not participate in the structured programme served as controls. Body weight, BMI, and fitness were evaluated at baseline, and after the 3 and 6 months intervention. Body weight and BMI were significantly reduced (P

Childhood obesity is associated with unfavorable lipid profile, suggesting that obese children should be screened for hypercholesterolemia. However, the prevalence of hypercholesterolemia in childhood obesity, and the effect of the degree of obesity on lipid profile, are unknown. Eighty-nine obese children and adolescents (BMI85%, mean age 10.4 +/- 2.5 years) and 53 non-obese control children matched for age, gender and pubertal stage participated in the study. Early morning blood samples for serum lipids were collected in all children after a 12-h fast. Mean serum cholesterol and triglycerides (TG) levels were significantly higher (p0.05) among the obese children (cholesterol: 175.2 +/- 31.4 vs 143.3 +/- 24.3 mg/dl; TG: 122.8 +/- 69.7 vs 94.3 +/- 37.8 mg/dl in obese and control children, respectively). Among the obese children, 52% had elevated serum cholesterol levels (170 mg/dl) compared to 16% in the controls. The degree of obesity (BMI 85-95% vs BMI95%) had no effect on serum lipids. Unfavorable lipid levels were relatively common among obese children, suggesting that obesity should be considered a risk factor for hypercholesterolemia, and that screening obese children for hypercholesterolemia should be considered.

A 4-year-old Jewish boy presented with dysuria, urinary dribbling, increased urinary frequency, and new onset of diurnal enuresis. An infiltrating solid mass involving the entire bladder wall was found. Biopsy revealed “tumor-forming” eosinophilic cystitis, a rare bladder lesion of unclear cause. Antitoxocariasis treatment was unsuccessful. High-dose corticosteroids failed. The child’s clinical condition and bladder sonographic findings continued to deteriorate. Treatment with cyclosporin A was given for 8 months, with a complete clinical, radiologic, and histopathologic cure and no side effects. Two years of follow-up showed a complete recovery.

Ambulatory blood pressure monitoring (ABPM) was performed in 29 children, ages 8.5-10.5 years (mean 11.6+/-3.0) with isolated haematuria (IH) and in 27 age, sex, weight and height matched healthy controls (C). Isolated haematuria was defined asor=5 RBC/HPF on three separate urinalyses over a 3-month period with normal renal function, a normal appearing ultrasound examination of the kidneys and the absence of hypercalciuria. Haematuria had been documented for at least 3 years prior to ABPM. Daytime and nighttime periods were 0800-2200 and 2200-0800 hours, respectively. The total number of successful blood pressure readings was 21.8 and 20.7 per subject (90.0 and 86.1% of all attempted measurements) in IH and C, respectively. Mean 24-h, daytime and nighttime heart rate, mean arterial pressure, and systolic and diastolic blood pressure in IH did not differ from that of controls. Nocturnal dipping was present in all IH patients and was of equal magnitude to C (9.5 vs 8.4 and 13.7 vs 10.3% for average systolic blood pressure (SBP) and diastolic blood pressure (DBP) dips, respectively). We conclude that normal blood pressure values, as well as the circadian rhythm of blood pressure, are maintained in children with IH of at least 3 years' duration.

Very few studies have examined the effect of childhood obesity on bone mineralization. The purpose of the present study was to determine bone strength by quantitative ultrasound (QUS) measurements of bone speed of sound (SOS) in obese children (n = 45; age range 6-17 yr). SOS was measured (by Sunlight Omnisense) in the mid-tibial and radial bones. Data were compared to age- and gender-matched norms of Israeli non-obese children. Radial and tibial SOS was significantly reduced in obese compared to non-obese children (p0.05). Bone SOS in obese children with BMI95th percentile was not significantly different from obese children with BMI from 85-95th percentile. Tibial and radial SOS were correlated with pubertal stage (r = 0.52, p0.005; and r = 0.35, p0.01, respectively), and with chronological age (r = 0.47, p0.005; and r = 0.32, p0.025, respectively). No significant correlation was found between endurance time as an indicator of fitness and bone SOS. Bone strength measured by QUS is reduced in obese children, but is not affected by the severity of obesity.

A 12-year-old boy presented with a limp and findings suggesting localised myositis of his right calf and a working diagnosis of Behcet disease was made. During 3 years of follow-up, he had another three episodes of calf myositis, all responsive to corticosteroids within days. Conclusion A case of recurrent localised myositis as a main manifestation of Behcet disease is reported. The evolution of incomplete Behcet disease, which is common in children, to the full blown form, with the emphasis on muscle involvement and the importance of early diagnosis of Behcet disease, is discussed.