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Biomedical subjects

Zvi Zadik

Publications and source records attributed to Zvi Zadik.

At least 19 recordsLinked to original sources
PubMed2006

Proximal 19q trisomy: a new syndrome of morbid obesity and mental retardation.

AIMS: To report on the clinical and metabolic characteristic and the unique chromosomal defect of a mentally retarded and morbidly obese patient. METHODS: A 13-year follow-up, including insulin sensitivity, lipid profile and polysomnography studies and various therapeutic interventions are described. The presence of a supernumerary marker in karyotype preparation was further studied by fluorescence in situ hybridization (FISH). Comparative genomic hybridization (CGH) was used to identify the source of the chromosomal marker. RESULTS: Insulin resistance was found by the homeostatic model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). M-FISH identified euchromatin derived from chromosome 19, and CGH confirmed the FISH results and demonstrated that the supernumerary marker derived from 19q12 to 19q13.2. CONCLUSION: The clinical and metabolic characteristics in association with partial chromosomal trisomy differ our patient from the currently known syndromes of obesity and mental retardation. The metabolic impairments in this case can derive from unbalanced expression of several genes in the 19q12-19q13.2 region, genes that are related to adipose tissue homeostasis and insulin resistance. The clinical and genetic similarities to a previously reported case may suggest that partial 19q trisomy is a new syndrome of obesity and mental retardation.

Adolescent↗
PubMed2006

Growth hormone/JAK-STAT axis signal-transduction defect. A novel treatable cause of growth failure.

Primary cultured fibroblasts of four patients with idiopathic short stature and severe growth delay, which displayed normal growth hormone receptor expression presented a reduced ability for activation of signal transducer and activator of transcription-3 (STAT3). Impaired STAT3 activation was accompanied by cell-cycle arrest at the Go /G1 phase. Increased levels of the cyclin-dependent kinase inhibitor, p21(WAF/CIPI), and reduced levels of cyclins were also detected in these patients. High concentrations of human growth hormone (1000 ng x mL(-1)) added to the culture medium induced activation of STAT3 and reduced the levels of p21(WAF/CIPI) in the fibroblasts of the four idiopathic short stature children. Treatment of these children with exogenous human growth hormone significantly augmented their growth velocity. Overall, our study provides the first evidence linking the idiopathic short stature phenotype with a functional aberration in the growth hormone signal transduction cascade which can be successfully overcome by exposure to high doses of growth hormone.

Base Sequence↗
PubMed2006

Familial Mediterranean fever and growth: effect of disease severity and colchicine treatment.

OBJECTIVE: To evaluate the effect of disease severity and colchicine treatment on height and weight parameters in children with familial Mediterranean fever (FMF). METHODS: Thirty prepubertal children (19 M, 11 F) were studied retrospectively. Z-score values of height, growth velocity, weight and body mass index were obtained over 1.84 +/- 1.14 years before and 2.58 +/- 1.55 years during colchicine therapy. Disease severity was evaluated by a specific score for FMF. RESULTS: By comparison to growth before treatment, during colchicine therapy height SDS increased from -1.00 +/- 1.17 to -0.54 +/- 0.96 (p < 0.001) and weight SDS increased from -0.74 +/- 1.09 to -0.47 +/- 1.06 (p = 0.008). An effect of disease severity on growth pattern could not be detected. Height SDS during therapy was negatively correlated with age at colchicine initiation. CONCLUSIONS: Colchicine therapy has a positive effect on both height and weight parameters in children with FMF. Early initiation of treatment is beneficial for height gain.

Anti-Inflammatory Agents↗
PubMed2005

Beta-adrenergic hyperresponsiveness in compensated hypothyroidism associated with Down syndrome.

Although compensated hypothyroidism (CH) is the most common thyroid impairment in Down syndrome (DS), its pathogenesis remains elusive. Because primary gonadal failure is another DS-associated endocrinopathy, we hypothesized that an impaired signal-transduction pathway shared by several organs may provide a unifying explanation for both endocrinopathies. We assessed two possible transduction-pathway components associated with CH in DS: the G-protein adenylate-cyclase (AC) system and beta-adrenergic responsiveness, previously reported to be enhanced in DS fibroblasts. Twenty-one DS patients and 14 control subjects were studied. Peripheral mononuclear cells (PMCs) were incubated with G-protein modulators [prostaglandin E1 (PGE1) and cholera toxin (CTx)], an AC stimulator (forskolin), and a beta-adrenergic agonist (isoproterenol), and cAMP levels were determined. All participants had normal plasma thyroid hormone levels, but 11 of the DS patients had elevated TSH levels (hTSH), whereas in the 10 others, they were normal (nTSH). cAMP levels in response to forskolin, PGE1, and CTx were similar in all groups, whereas isoproterenol-stimulated cAMP levels were significantly higher in the hTSH group than in the nTSH group and control subjects (45 +/- 30 versus 22 +/- 9 and 21 +/- 9 pmol . 10(6) cells(-1) . 10 min(-1), respectively; p = 0.02). Four patients in the DS hTSH subgroup had impaired sexual development. We found hyperresponsiveness of PMCs to a beta-adrenergic agonist in a subgroup of DS patients with CH. If this observation is applicable to the thyroid gland, then it may reflect a mechanism in which negative effects on cell growth or responsiveness to TSH lead to CH.

Adenylyl Cyclases↗
PubMed2005

Effect of nutrition on growth in short stature before and during growth-hormone therapy.

OBJECTIVE: Although nutritional counseling is an integral part of the management of rapidly growing children, few studies have focused on the importance of nutritional supervision during growth-hormone (GH) therapy. The objective of this study was to study the effect of caloric intake on growth before and during GH therapy. METHODS: A total of 115 short normal prepubertal children who were 7.4 +/- 1.2 years of age (mean +/- SD) and had height SD score (SDS) of -2.5 +/- 0.6 were treated with a GH dose range of 0.13 to 0.52 mg/kg per week for 1 year. A 3-day nutritional recall and blood chemistry analysis were repeated every 3 months. RESULTS: Caloric intake (expressed as % recommended dietary allowance) was positively correlated with the pretreatment growth velocity (SDS) and the increment in growth velocity SDS during the first year of GH therapy (r = 0.363 and 0.493). By stepwise regression analysis, we identified 4 parameters that could predict the 1-year increment in growth velocity SDS: the contribution of each factor (% variability) was pretreatment growth velocity SDS 36%, GH dose (27%), caloric intake 4%, and the integrated concentration of GH 2% (r(2) = 0.689). GH therapy induced an alkaline phosphatase increment of 59 +/- 49 IU/mL, an insulin-like growth factor-I increment of 32.6 +/- 11.9 nmol/L, and a GH binding protein increment of 10.2 +/- 2.7%. During GH therapy, an increase in serum transferrin (56.5 +/- 35.2 mg/dL) and a decrease in serum iron (20.5.5 +/- 20.2 microg/dL) were noted. These changes could not be detected through hemoglobin levels or hematopoietic indexes. Dietary iron supplementation reversed this phenomenon. CONCLUSIONS: The nutritional status of GH-treated patients before and throughout the course of GH treatment should be monitored closely to improve the growth response and prevent nutritional deficiencies. Special emphasis should be placed on iron nurture.

Alkaline Phosphatase↗
PubMed2005

Longitudinal monitoring of bone measured by quantitative multisite ultrasound in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is characterized, among other features, by intestinal malabsorption of minerals, vitamins, and various food ingredients. This may cause a suboptimal peak bone mass and thereby susceptibility to osteoporosis at an early age. OBJECTIVE: Longitudinal measurement of bone in CD during active disease and during remission. DESIGN: We evaluated 24 patients with CD (16 males) 14 to 16 years of age longitudinally, every 3 months over 12 months, for disease activity. Longitudinal follow-up by quantitative ultrasound measurement using a bone sonometer (Sunlight Omnisense, Tel Aviv, Israel) that obtains axial speed of sound (SOS) was also performed. Eight of the CD patients were in remission (R-CD), characterized by accelerated weight and height gain and near-normal erythrocyte sedimentation rate and serum iron. Eight patients had active CD (A-CD), and 8 patients were under treatment with oxandrolone. RESULTS: By two-way repeated-measures analysis of variance, the change in SOS Z-score of tibia at 0, 6, and 12 months was as follows: -0.5 +/- 0.2 to -0.3 +/- 0.2, -0.6 +/- 0.2 to -1.0 +/- 0.5 and -0.6 +/- 0.2 to -0.4 +/- 0.2 in the remission, active disease, and oxandrolone-treated groups, respectively (P < 0.001). Similarly, the change in SOS Z-score of radius during the study was as follows: -0.5 +/- 0.3 to -0.6 +/- 0.3, -0.6 +/- 0.3 to -1.0 +/- 0.3 and -0.6 +/- 0.2 to -0.4 +/- 0.2 in the remission, active disease, and oxandrolone-treated groups, respectively (P < 0.001). While a small change over time in patients in remission was noted, SOS decreased in patients with active disease and increased in oxandrolone-treated patients. Despite the fact that SOS remained in the normative range in all patients, a clear deterioration was demonstrated for patients with active disease. CONCLUSIONS: We conclude that longitudinal follow-up of patients with active disease may detect an early pattern of deterioration in quality of bone.

Adolescent↗
PubMed2004

Longitudinal monitoring of bone accretion measured by quantitative multi-site ultrasound (QUS) of bones in patients with delayed puberty (a pilot study).

OBJECTIVE: to compare the effect of anabolic agents on bone accretion in boys with constitutional delay of puberty (CGDP). RATIONALE: it has been suggested that an appropriate timing of puberty is necessary for normal bone mineral density (BMD) acquisition. Proper bone development during childhood is the key factor in achieving higher peak bone mass during middle age, which may not be achievable in CGDP children, and thereby osteoporosis may appear at an earlier age then expected. PATIENTS AND METHODS: 45 boys with CGDP aged 14-16 years were monitored longitudinally, every 3 months over 12 months with Sunlight Omnisense, a quantitative ultrasound device (Tel Aviv, Israel). The apparatus is a multi-site bone sonometer that obtains axial Speed of Sound (SOS). Based on a reference database obtained on n=1,085 (490 boys) 0-18 years, a normative curve was determined. Fifteen (14-16 years old) of the CGDP patients were treated with I.M. testovirone depot 100 mg monthly for 6 months, 15 (14-16 years old) were treated with oxandrolone 5 mg/m(2) daily for 6 months, and 15 (14-16 years old) were in an observation group. RESULTS: whereas the quantitative ultrasound (QUS) Z-score had shown some increase over time in CGDP-treated patients, an increase was found in tibia Z-score from -0.5(-0.64, -0.36) to -0.4(-0.54, -0.26) and from -0.52(-0.67, -0.38) to -0.31(-0.44, -0.11) in the testosterone and oxandrolone-treated groups, respectively, [median (25%, 75%)]. An increase in radius Z-score from -0.52(-0.65, -0.25) to -0.4(-0.54, -0.15) and from -0.51(-0.61, -0.21) to -0.37(-0.47, -0.07) in the testosterone- and oxandrolone-treated groups respectively [median (25%,75%)]. Z-score SOS decreased in the observation group -0.5(-0.66, -0.3) to -0.69(-0.85, -0.54) and -0.5(-0.59, -0.41) to -0.81(-0.95, -0.55) in tibia (P = 0.032) and radius (P = 0.029), respectively. Despite the fact that QUS remained in the normative range in all patients, a clear deterioration was demonstrated in untreated CGDP patients. CONCLUSION: longitudinal follow-up of patients with CGDP may detect an early pattern of deterioration of bone mass.

Adolescent↗
PubMed2004

Childhood obesity.

In March 2004 a group of 65 physicians and other health professionals representing nine countries on four continents convened in Israel to discuss the widespread public health crisis in childhood obesity. Their aim was to explore the available evidence and develop a consensus on the way forward. The process was rigorous, although time and resources did not permit the development of formal evidence-based guidelines. In the months before meeting, participants were allocated to seven groups covering prevalence, causes, risks, prevention, diagnosis, treatment, and psychology. Through electronic communication each group selected the key issues for their area, searched the literature, and developed a draft document. Over the 3-d meeting, these papers were debated and finalized by each group before presenting to the full group for further discussion and agreement. In developing a consensus statement, this international group has presented the evidence, developed recommendations, and provided a platform aimed toward future corrective action and ongoing debate in the international community.

Child↗
PubMed2004

Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2.

Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Recently, activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 were identified in 10 PNDM patients. Tolbutamide-stimulated insulin secretion, demonstrated in 3 of these patients suggested that some PNDM patients may respond to oral sulfonylurea treatment. In this report, we describe an infant with PNDM due to an arginine-to-histidine substitution at position 201 (R201H) of the gene encoding Kir6.2. After insulin pump therapy for six months, he was shifted to oral glybenclamide therapy at a daily dose of 0.8 mg/kg. Basal c-peptide level increased by two fold during glybenclamide treatment, but no further elevation was observed following intravenous glucose administration. Outpatient, continuous glucose monitoring while on a normal infant diet demonstrated a marked improvement in glycemic control. This study demonstrates the feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy, and the superiority of this approach over insulin administration.

Blood Glucose↗
PubMed2003

Pediatric reference curves for multi-site quantitative ultrasound and its modulators.

More than 85% of peak skeletal mass is accrued by the age of 18 years, making bone growth during childhood and adolescence a critical process. The purpose of this study is to establish pediatric reference curves for bone Speed of Sound (SOS) as measured by multi-site quantitative ultrasound. Analysis was performed on a total of 1085 healthy subjects ages 0-18 years (595 females, 490 males). Demographic and anthropometric parameters (height and weight), as well as data on calcium intake and physical activity, were collected. Ultrasound bone measurements were performed at the mid-shaft tibia and the distal third of the radius (Sunlight Omnisense 7000P). An age-related speed of sound (SOS) curve that describes SOS changes at the tibia and radius in both genders was demonstrated. SOS showed a steep increase during the first 5 years of life in both genders at the tibia and radius. The period between the ages of 6-11 years is characterized with a very shallow increase in SOS at both sites. Thereafter, during the pubertal period, there is a second growth burst in SOS, starting at age 11 for girls and age 14 for boys. No significant meaningful correlation was found between the anthropometric parameters (height, weight and BMI) and the SOS measurements after the age parameter was controlled. Subjects who reported low physical activity levels were found to have lower Z-scores than their counterparts (P<0.05). The SOS of pre-menarche girls was significantly lower than that of post-menarche girls at the radius and tibia (P<0.05). The level of calcium intake did not correlate with bone SOS. Intra-operator precision measurements were 0.36% (0.25-0.47%) at radius and 0.30% (0.20-0.40%) at the tibia. To date, there is no widely accepted classification or clinical working guidelines for children's bone health assessment or prediction of fracture risk based on bone strength measurements in children. This study establishes a pediatric reference curve for the Omnisense, and therefore supports the feasibility of using Sunlight Omnisense 7000P, a multi-site bone sonometer, for the assessment of pediatric bone properties. Further studies mainly in different diseased children groups should further support the use of such a basic tool for clinical evaluation, assisting the physician to work towards healthy bones for his patients.

Adolescent↗
PubMed2003

Adult height and weight of breast-fed and bottle-fed Israeli infants.

BACKGROUND: Breast-fed infants grow more slowly than bottle-fed infants. This growth deceleration sometimes alarms health care personnel to the point of considering other forms of nutrition. OBJECTIVES: To evaluate the final adult anthropometric outcome associated with breast or formula feeding during infancy. DESIGN: Height and weight data were collected from eight well-baby clinics representing various ethnic origins, lifestyles, and socioeconomic backgrounds. Children were measured every 1 to 2 months for the first 6 months, every 3 months until 2 years of age, and yearly thereafter, until they reached their final height. Longitudinal data were collected from 1960 healthy children (961 boys). Overall, 613 of the children were breast fed for 1 year and 218 for 6 months. RESULTS: The magnitude of the decline in Z scores of breast-fed vs. bottle-fed infants, between birth and 1 year of age was not as great for height as for weight -0.2 and -0.3 respectively, and disappeared at 2 years of age. The weight for height decreased between birth and the end of the first year in breast-fed children by 0.3 (Z score). Children switched to bottle feeding exhibited a growth spurt. However, there was no difference in the final heights or weights of breast-fed children compared with bottle-fed children 165.3 +/- 6.2 (n = 134) versus 164.9 +/- 6.4 (n = 195) in females, respectively, and 175.3 +/- 6.8 (n = 122) versus 175.8 +/- 7.1 (n = 162) in males, respectively. Adult obesity in this sample population (n = 637) was correlated with maternal obesity. Maternal BMI SD correlated with offspring BMI SD at 18 years of age (r = 0.873, P < 0.001) but not with breast feeding. Adult BMI was similar between the breast-fed and bottle-fed groups. CONCLUSIONS: Despite their slower growth rate, breast-fed children reach the same final height as bottle-fed children. Breast-fed infants should be monitored according to specifically designed growth charts. Obesity in adult life is correlated with factors not related to breast feeding.

Body Height↗
PubMed2002

Decreased growth during therapy with selective serotonin reuptake inhibitors.

BACKGROUND: There is no information on the effects of selective serotonin reuptake inhibitors (SSRIs) on growth and puberty in children. We examined growth and growth hormone secretion in 4 children treated with SSRIs for various psychiatric disorders. DESIGN: Case study. PARTICIPANTS: Four children (3 boys) aged 11.6 to 13.7 years with obsessive-compulsive disorder or Tourette syndrome. MAIN OUTCOME MEASURES: Growth, pubertal progression, and hypothalamic pituitary function. METHODS: The patients were treated with SSRIs for 6 months to 5 years (dosage, 20-100 mg/d). All were regularly examined for changes in height and bone age and for pubertal progression. They also underwent evaluation of somatotrophic axis and hypothalamic-pituitary axis function. RESULTS: All 4 patients had growth attenuation. Three of them exhibited growth retardation at a pubertal stage when a growth spurt was anticipated. Three had a decreased growth hormone response to clonidine hydrochloride stimulation and 2 to both clonidine and glucagon stimulation, and 1 had decreased 24-hour secretion of growth hormone that normalized when therapy was stopped. The rest of the endocrine evaluations were within reference ranges in all patients. At follow-up, 2 patients were being treated with somatropin while continuing SSRI therapy, and the other 2 resumed normal growth after discontinuation of therapy. CONCLUSIONS: A decrease in growth rate, possibly secondary to suppression of growth hormone secretion, may occur during SSRI therapy. As the use of this group of drugs is expected to increase in the young age groups, larger studies are warranted to investigate their effect on growth and growth hormone secretion.

Adolescent↗
PubMed2002

[New approaches in the treatment of short stature].

Over the past years, the efforts to improve the final height of children with short stature has yielded new modalities of therapy. New types of injection devices, mainly ready-to-use injection pens with multi-dose vials of reconstituted growth hormone (GH), have made the treatment technically easier and less stressful for the patients. A new type of slow-release GH injected once or twice a month has recently been studied. In addition, several types of synthetic GH-secretagogues were examined, with the advantage of being introduced by the oral or nasal route. The recognition of the pivotal role of estrogens in skeletal maturation and subsequent growth arrest, was the basis for the use of aromatase inhibitor in a pioneering study, with promising results. We have concluded the review with an update on the benefit of GH therapy in children with normal short stature, based on 12 studies that provided data on the final height of these children.

Child↗
PubMedDate not supplied

The emergence and treatment of anorexia and bulimia nervosa. A comprehensive and practical model.

UNLABELLED: The objective was to propose and describe a new bio-psycho-social model of emergence and maintenance of anorexia nervosa and bulimia nervosa, and demonstrate its application to treatment. An original model, based on literature review and our own clinical experience, was created. Therapeutic guidelines were derived from the theoretical model and applied in the treatment of 97 anorexia and bulimia nervosa patients presented at the eating disorders unit at Kaplan Hospital in Israel over 18 months. A team comprising a pediatrician, a child psychiatrist, a dietician, and trained nurses collaborated in a comprehensive systemic therapeutic approach involving parents, schools, and community agents. RESULTS: Ninety-one girls and six boys were treated in the eating disorder unit (55 had AN, 29 had BN and 13 had EDNOS). Thirty-seven patients were hospitalized and sixty were treated in the outpatient clinic. Mean hospitalization time of the first five patients was 108 days. Mean hospitalization time of the remaining 32 patients was reduced to 32 days. The mean number of outpatient clinic interventions was 12. At the one-year follow up, 74 patients were doing well in all respects. Fourteen patients still needed a lot of supervision in eating. Five are still hospitalized and four were lost to follow up. CONCLUSIONS: The proposed model proves to be more than just another theory in that it is successfully applied in treatment. Short systemic therapy is very effective. The longer the delay in drastic, aggressive treatment, the worse the prognosis. Extended hospitalization periods worsen the prognosis. Weakness of the parental unit is a strong indication for inpatient care. The longer the experience in treating eating disorders, the shorter the hospitalization and number of interventions.

Adolescent↗