Yardena Danziger

Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone

Summary:  Purpose: To evaluate the outcome of children with cryptogenic infantile spasms treated with high‐dose synthetic adrenocorticotropic hormone (ACTH) and the relation between early treatment, within 1 month of onset, and outcome.

Association of anorexia nervosa with the high activity allele of the COMT gene: a family-based study in Israeli patients.

Anorexia nervosa (AN) is a common, severe and disabling psychiatric disorder, characterized by profound weight loss and body image disturbance.1 Family and twin studies indicate a significant genetic contribution2,3 and pharmacological data suggest possible dysfunction of the serotonergic4,5 and dopaminergic6–9pathways. Catechol-O-methyltransferase (COMT) is a candidate gene for mediating susceptibility to AN since it is involved in the dopamine catabolism10 and because its functional polymorphism (Val/Met 158) determines high (H) and low (L) enzymatic activity alleles.11 Fifty-one Israeli AN patients and their parents were genotyped with the COMT polymorphism. Using the haplotype relative risk (HRR) method it was found that the frequency of the H allele among alleles transmitted to AN patients from their parents was significantly higher than in those not transmitted (68% vs 51% χ2 = 5.20, df = 1, P = 0.023, odds ratio: 2.01). Transmission disequilibrium test (TDT) revealed that out of 49 heterozygote parents the H allele was transmitted to AN patients 33 times while the L allele was transmitted only 16 (McNemars χ2 = 5.90, df = 1, P = 0.015). Our study suggests that the COMT gene is associated with genetic susceptibility to AN, and that individuals homozygous for the high activity allele (HH) have a two-fold increased risk for development of the disorder.

Scrotal involvement in Henoch-Schönlein purpura in children

Different rates of scrotal involvement in Henoch-Schonlein purpura (HSP) have been reported. We assessed scrotal involvement in 86 children over a 20-year period: 10 patients suffered from scrotal involvement and 9 of them also had arthritis. The possible association between scrotal involvement and arthritis may help the physician in the differential diagnosis of atypical presentations.

Reduction of serum theophylline levels by terbutaline in children with asthma

We studied the effect of oral terbutaline on serum theophylline levels in 12 children with asthma. Sustained‐release theophylline (10 mg/kg twice a day) was given with placebo or terbutaline (0.075 mg/ kg three times a day) in a chronic, randomized, double‐blind, crossover design. The trough serum theophylline concentration fell from 13.8 ± 4.0 to 10.8 ± 3.6 μg/ml and the peak expiratory flow rate increased from 285 ± 30 to 310 ± 29 L/min after terbutaline. Further investigation is needed to clarify the mechanism of action by which terbutaline decreases serum theophylline levels.

Haplotype analysis of the COMT-ARVCF gene region in israeli anorexia nervosa family trios

Anorexia nervosa (AN) is a severe and complex psychiatric disorder with a significant genetic contribution. Previously, we found an association between AN and the 158Val/Met polymorphism of the catechol‐O‐methyltransferase (COMT) gene in a family‐based study of 51 Israeli AN trios. In the present study, we extended the original sample to include 85 family trios [66 AN restricting (AN‐R) and 19 bingeing/purging (AN‐BP) subtype] and performed a family‐based transmission disequilibrium test (TDT) analysis for five SNPs in the COMT and two in the adjacent ARVCF gene. Association was found between AN‐R and several SNPs in the COMT‐ARVCF region including the 158Val/Met polymorphism. TDT analysis of 5‐SNP haplotypes in AN‐R trios revealed an overall statistically significant transmission disequilibrium (P < 0.001). Specifically, haplotype B [COMT‐186C‐408G‐472G(158Val)‐ARVCF‐659C(220Pro)‐524T(175Val)] was preferentially transmitted (P < 0.001) from parents of AN‐R patients to their affected daughters, while haplotype A [COMT‐186T‐408C‐472A(158Met)‐ARVCF‐659T(220Leu)‐524C(175Ala)] was preferentially (P = 0.01) not transmitted. Haplotype B was associated with increased risk (RR 3.38; 0.95CI 1.98–6.43) while haplotype A exhibited a protective effect (RR 0.40; 0.95CI 0.21–0.70) for AN‐R. Preferential transmission of the risk alleles and haplotypes from the parents was mostly contributed by the fathers. No significant transmission disequilibrium of alleles or haplotypes was found for AN‐BP trios. The risk and protective haplotypes may carry molecular variations in the COMT gene or its vicinity that are relevant to the pathophysiology of restrictive anorexia nervosa in the Israeli‐Jewish population.

CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: A case-control study of female patients and several ethnic groups in the Israeli Jewish population

The human small‐conductance Ca2+‐activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family‐based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co‐morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case‐control analysis that has demonstrated a significant over‐representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co‐morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive‐compulsive disorder (OCD) co‐morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.

Cricopharyngeal dysfunction in childhood: treatment by dilatations.

A 3-year-old child with Cricopharyngeal dysfunction is reported. Swallowing difficulties, nasal regurgitation, and gagging developed at 2 months of age. Repeated aspirations and over 40 episodes of pneumonia necessitating multiple hospitalizations occurred up to 2 years of age, along with pharyngcal pooling of saliva and inability to swallow solid food. Barium was held up at the Cricopharyngeal level, and a prominent esophageal impression was seen at the same level. Symptoms were completely alleviated after two esophageal dilatations by mercury dilators, and the relief persisted for the 6 months of follow-up. The diagnosis of Cricopharyngeal dysfunction is discussed, and the necessity for manometric studies, in the face of often misleading radiologic appearance, is emphasized. It is suggested that early use of esophageal dilatations might prevent prolonged morbidity and afford long-term symptomatic relief.

Is psychotherapy mandatory during the acute refeeding period in the treatment of anorexia nervosa

Forty-five adolescent and preadolescent patients (42 females, three males) with anorexia nervosa (AN) were treated in a pediatric day care unit of a large urban hospital by a multidisciplinary team. In our treatment model, the pediatrician has the responsibility for the initial evaluation and physical rehabilitation while the pediatric psychiatrist does the initial evaluation of the patient and family and is available for intervention in an emergency. Parents are actively involved in the treatment program. Family psychotherapy is recommended for each patient and his or her family. Among 45 patients, 24 did not enter psychotherapy during the first 2 months of the refeeding period, while the remaining 21 patients started psychotherapy (family and/or individual) during this period. Weight gain was higher in the group without formal psychotherapy during the initial period of refeeding (7.3 +/- 3.1 kg versus 5 +/- 2.5 kg; p less than 0.01). It is suggested that the initiation of structured psychotherapy is not mandatory and does not contribute to treatment effectiveness in the acute phase when emaciation and negativism may hinder the psychotherapeutic process. We believe a multidisciplinary team, together with the parents, is the treatment of choice during the acute phase of AN.

Non-interaction of ketotifen and theophylline in children with asthma – an acute study

SummarySix asthmatic children participated in an acute crossover randomized study. They received a single dose of aminophylline syrup 6 mg/kg after having received ketotifen syrup 1 mg b.i.d. or place-bo for 8 days. Ketotifen did not significantly affect the heart rate, pulse pressure or such pharmacokinetic parameters of theophylline as peak serum level, time to peak, half life and AUC. Thus, ketotifen had no significant effect on the disposition of theophylline.

Association between a common CYP17A1 haplotype and anxiety in female anorexia nervosa

Dehydroepiandrosterone (DHEA), the main brain neurosteroid, has been implicated in various psychiatric disorders especially those including gender differences. We studied genetic variability in the DHEA-producing enzyme CYP17A1 in relation to anorexia nervosa (AN) susceptibility and AN-related co-morbidities. We performed analysis of 100 Israeli AN family trios accounting for CYP17A1 haplotypes characteristic of populations of European origin and studied genotype–phenotype relationships using correlation analyses and transmission disequilibrium test. Although our analysis revealed no evidence of association between CYP17A1 and AN per se, it revealed an association between specific CYP17A1 haplotypes and AN co-morbidity, specifically anxiety. We found that a common CYP17A1 haplotype (H1) was associated with higher anxiety in AN patients (Clinical Global Impression; CGI-anxiety ≥4). Moreover, H1 homozygotes were at higher risk for expressing high CGI-anxiety levels (OR = 3.7), and H1 was preferentially transmitted to AN patients with high CGI-anxiety levels (P = 0. 037). We suggest that CYP17A1 H1 haplotype may contribute to genetic predisposition to higher CGI-anxiety levels in AN patients and that this predisposition may be mediated by reduced CYP17A1 enzymatic activity and corresponding lower DHEA production.