Baclofen reverses the reduction in prepulse inhibition of the acoustic startle response induced by dizocilpine,but not by apomorphine

Rationale Since baclofen, the prototypical GABA_B receptor agonist, is known to reduce the activity of dopaminergic mesolimbic neurons, a putative antipsychotic property of this compound has been suggested, but the evidence for this is still controversial.Objectives The aim of the present study was to elucidate the effects of baclofen on the prepulse inhibition (PPI) of the acoustic startle response (ASR), a behavioral paradigm considered to be one of the most powerful tools for the evaluation of sensorimotor gating and for the screening of antipsychotics.Methods We tested the effects of baclofen (1.25, 2.5, 5 and 10 mg/kg IP) in rats, per se and in co-treatment with some of the substances known to induce a robust reduction of PPI, such as apomorphine (0.25 mg/kg SC) and dizocilpine (0.1 mg/kg SC). Finally, in order to ascertain whether the effects of baclofen could be ascribed to its activity on GABA_B receptors, we analyzed whether its action could be prevented by pretreatment with SCH 50911, a selective GABA_B receptor antagonist (20 mg/kg IP). All the experiments were carried out using standard procedures for the assessment of PPI of the ASR.Results Baclofen per se produced no significant change in PPI parameters. Moreover, while no effect on apomorphine-mediated alterations in PPI parameters was observed, baclofen proved able to reverse dizocilpine-induced PPI disruption, and this effect was significantly prevented by SCH 50911. On the other hand, this last compound exhibited no effects per se at the same dose.Conclusions These results indicate that GABA_B receptors are implicated in the neurobiological circuitry accounting for glutamatergic action in sensorimotor gating, and therefore can be proposed as putative new targets in the pharmacological therapy of psychotic disorders. Further studies should be addressed to evaluate more closely the clinical efficacy of baclofen in this respect.     

Autoimmune thyroid disease and celiac disease in children

BACKGROUND: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. METHODS: Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered. RESULTS: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). CONCLUSIONS: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.     

Maintenance of B lymphocyte-related clones in the cerebrospinal fluid of multiple sclerosis patients

A longitudinal study of Ig V gene segments utilized by B cells from the cerebrospinal fluid (CSF) of two patients with multiple sclerosis (MS) was carried out using RT-PCR methodologies. One patient with a relapsing-remitting (RR)-MS was investigated at onset and at relapse, 1 year later. A patient with secondary-progressive (SP)-MS was tested 9 and 13 years after disease onset. Sequence analyses of V(H)DJ(H) segments bearing V(H)3 and V(H)4 that were obtained from Cgamma cDNA genes demonstrated a substantial proportion of shared clones in the samples taken at different times; these clones were identical or closely related, i.e. had the same third complementary determining region (CDR) of the H chain variable region gene (HCDR3) with different mutations in the V(H) segment. Collectively, these data demonstrate that in MS patients there is a strong selective pressure, which could be exerted by antigen (or autoantigen) stimulation, for the maintenance and partial diversification of certain V(H)DJ(H) Cgamma sequences.     

Effect of highly purified urinary follicle-stimulating hormone on oocyte and embryo quality

OBJECTIVE: To determine the effects of ovarian stimulation with highly purified urofollitropin on oocyte and embryo quality. DESIGN: Parallel randomized open-label clinical study. SETTING: Assisted reproduction centers. PATIENT(S): Two hundred sixty-seven infertile couples undergoing IVF/ICSI. INTERVENTION(S): All participants underwent standard down-regulation with GnRH analogue. One hundred thirty-three participants received highly purified urinary FSH and 134 controls received recombinant FSH. MAIN OUTCOME MEASURE(S): Primary end points were number of morphologically mature oocytes retrieved, embryo quality, and pregnancy and implantation rates. Secondary end points were: total number of days of FSH stimulation, total dose of gonadotropin administered, fertilization rate per number of retrieved oocytes, embryo cleavage rate, live birth and miscarriage rates, endometrial thickness and estradiol level on the day of hCG administration, cancellation rate, and incidence of moderate or severe ovarian hyperstimulation syndrome. RESULT(S): Pregnancy and implantation rates were nonsignificantly higher in the urinary FSH group than the recombinant FSH group (46.5% vs. 36.8% and 22.1% vs. 15.8%, respectively). The grade 1 embryo score was significantly higher in the urinary FSH group than the recombinant FSH (42.1% vs. 33.5%), and the live birth rate was nonsignificantly higher in the former group. CONCLUSION(S): Highly purified urinary FSH is as effective, efficient, and safe for clinical use as recombinant FSH.     

Developmental changes of HT7 expression in the microvessels of the chick embryo brain

The neurothelin/HT7 antigen is a chick-specific, cell-surface glycoprotein expressed by the brain endothelial cells and widely utilized in experimental studies as a marker of barrier-provided vessels. Previous immunohistochemical studies have demonstrated that HT7 is already expressed in the embryonic brain vessels and that it is first detectable on embryonic day 10 and developmentally regulated. In the present study, the vascular expression of HT7 was investigated in different regions of the central nervous system from the 5th day right up to the latest stage of the chick embryo development. The study was carried out utilizing a monoclonal antibody anti-HT7, which was detected by both enzymatic and fluorescent immunohistochemical methods. The observations demonstrated the presence of HT7-stained vessels as early as embryonic day 6 in the rhombencephalon and mesencephalon, and at embryonic day 9 in the prosencephalon. Regional differences were also evidenced within the rhombencephalon and mesencephalon, since the endothelial antigen HT7 was expressed earlier in the brain stem (tegmentum of the medulla oblongata, pons and mesencephalon) than in the cerebellum and optic tectum. The caudo-cranial and ventro-dorsal gradients of HT7 expression were temporally and spatially related to the development of the brain vessels. The early detection of HT7 staining in the choroid plexus epithelium and perineural vessel endothelium, sites of the blood-cerebrospinal fluid barrier and pial barrier, respectively, has confirmed this antigen to be a precocious marker for all the barrier systems in the brain.     

<Emphasis Type="Bold">Reproductive Endocrinology:</Emphasis> Uterine Perfusion and Hormonal Pattern in Patients with Polycystic Ovary Syndrome

Purpose: To evaluate whether polycystic ovary syndrome (PCOS) patients with different pulsatility index (PI) of uterine artery showed differences in their hormonal pattern. Methods: Eighty-eight PCOS-affected patients and 15 controls were submitted to Doppler flow measurement of uterine artery; LH, FSH PRL, estradiol, and androgens concentration determination; and BMI evaluation during early follicular phase. Results: The mean PI of uterine artery of PCOS patients was significantly higher than control group (2.97 ± 0.9 vs. 1.89 ± 0.2 respectively). The distribution of the PI'values was significantly different in the PCOS-affected patients and in control group. The plasma levels of DHEAS and BMI were significantly higher in PCOS patients with PI 3 than in PCOS patients with PI < 3. Conclusion: High resistance in the uterine artery is present in PCOS patients, but a wide range PI values of uterine artery is present. BMI and DHEAS seem to be factors interfering with uterine perfusion.     

The treatment of large supratentorial arachnoid cysts in infants with cyst-peritoneal shunting and Hakim programmable valve

OBJECTIVE: This retrospective case series examines 7 infants with large supratentorial arachnoid cysts who underwent cyst-peritoneal shunting and insertion of a Hakim programmable valve. Comparing pre- and postoperative clinical data, neuroradiological and regional cerebral blood flow (rCBF) findings we evaluated the efficacy of the surgical procedure. METHODS: Infants, ranging in age from 1 to 55 days (mean age 29.5 days), were assessed pre- and postoperatively by neurological examination, developmental profile and neuroimaging. RESULTS: Post procedure, all patients showed a significant reduction in the cyst/brain ratio on neuroimaging (p<0.001), 6 had a normal developmental profile (p<0.001) and 5 cases showed a significant amelioration of clinical symptoms and neurological signs. Two patients underwent preoperative SPECT scans, which showed hypoperfusion in the area surrounding the cyst; this decreased rCBF also improved post shunting. CONCLUSIONS: Large supratentorial arachnoid cysts in infants can be successfully treated with cyst-peritoneal shunting and insertion of a Hakim programmable valve. This is the first study specifically aimed at evaluating the long-term results of these conditions.     

Recurrent Abdominal Pain in Primary and Tertiary Care: Differences and Similarities

This study sought to identify child and parent characteristics differentiating children with recurrent abdominal pain seen by a pediatrician (RAP-Peds) from those seen by a gastroenterologist (RAP-GI). Children (7-10 years) and mothers in three groups (RAP-GI, RAP-Peds, and Controls) completed mother and child reports of child's functional disability, internalizing symptoms, and somatic complaints, and mother report of her anxiety and somatization. Child report did not differentiate groups. RAP mothers were more likely than Control mothers to focus on somatic complaints in themselves and their children. Mother report of child disability was strongly related to tertiary care for child's recurrent abdominal pain.     

Use and tolerability of newer antipsychotics and antidepressants: a chart review in a paediatric setting

Objective To analyse the prescribing pattern and the safety profile of different atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) during the years 2002–2003 in paediatric setting. Setting Two Child Neurology and Psychiatry Divisions of Southern Italy (University of Messina and “Oasi Institute for Research on Mental Retardation and Brain Aging” of Troina). Methods A retrospective chart review of all children and adolescents starting an incident treatment with atypical antipsychotics or SSRIs was performed. Within the first 3 months of therapy, any potential adverse drug reaction (ADR) was identified and the clinical outcome of psychotropic drug treatment was assessed. Main Outcome Measure Rate of ADR in the first 3 months of therapy with atypical antipsychotics and SSRIs in children and adolescents. Results On a total of 97 patients’ charts being reviewed, 73 (75%) concerned atypical antipsychotics and 24 (25%) SSRIs. Risperidone (N = 45, 62%) was the most frequently prescribed antipsychotic drug, followed by olanzapine (24, 32%). Overall, 50 (68%) antipsychotic users reported a total of 108 ADRs during the first 3 months of therapy, leading to drug discontinuation in 23 patients (31%). Among 24 users of SSRI, 12 (50%) received paroxetine, 6 (25%) sertraline, 5 (21%) citalopram and 1 (4%) fluoxetine. Only paroxetine users (21%) reported at least one ADR, however, none of SSRI users withdrew drug treatment within first 3 months. Conclusions ADRs occurred frequently during first 3 months of treatment with atypical antipsychotics and, to a lesser extent, with SSRIs in children and adolescents. Further investigations are urgently needed to better define the benefit/risk ratio of psychotropic medications in paediatric setting.