Comparative genomic hybridization in ganglioneuroblastomas.

The ganglioneuroblastoma are rare lesions with widespread neuronal differentiation that have been classified as intermediate stages between neuroblastoma and ganglioneuroma. To identify overall chromosome aberrations in ganglioneuroblastoma, we performed comparative genomic hybridization. All of the five tumor samples were found to exhibit multiple gains involving different chromosomal regions. Chromosomal gains displayed by chromosomes and chromosome loci were 2p25 approximately pter (60%), 5p15.1 approximately p15.3 (60%), 7 (60%), 13q22 approximately q31 (60%), and 22 (60%), which were detected as minimal common regions in all five tumor samples. Chromosome 22 gain, which had not been reported in neuronal tumors before, and novel site 13q22 approximately q31 may be considered to play an important role in progression and differentiation of ganglioneuroblastoma.     

Effect of melatonin in the prevention of post-operative adhesion formation in a rat uterine horn adhesion model

BACKGROUND: Our main aim was to investigate the effects of melatonin (ME), possibly the most powerful free-radical scavenger, on the prevention of i.p. adhesion formation in rat uterine horn. Our secondary aim was to determine whether different methods of administration of ME were beneficial. METHODS: Animals were randomly assigned into seven groups, each consisting of 13 rats. Measured serosal injury was created using a standard technique. While control and two sham groups were not given ME, two of the remaining four groups were given a single dose of 10 mg/kg (2 mg) of ME i.p. immediately after injury and 30 min prior to injury respectively. In the two other groups, ME treatment was continued daily for 5 days. All animals were killed 2 weeks after surgery and adhesions were determined and scored by a examiner blinded to the test. RESULTS: The extent, severity and total scores of adhesion were found to be significantly reduced in all of the ME treatment groups when compared with control and sham groups. There were no statistically significant differences between the treatment groups. CONCLUSIONS: This study showed that even single dose ME therapy was effective in the prevention of post- operative i.p. adhesion formation.     

Suicide attempts and risk factors among children and adolescents

The purpose of this study was to determine the prevalence of suicide attempts, and to identify the risk factors for suicide attempts in Turkish children and adolescents between the ages 10 and 20 years. Multi-step, stratified, cluster sampling was used. A stratified sample of 4256 students was selected as representative of the city's school children population. Data was obtained with a pair of structured questionnaires designed to evaluate the presence and risk factors of suicide attempts, both in the children and adolescents and their parents. These questionnaires investigated family environment, subject characteristics, and various risk factors for suicide attempts. Child Beck Depression Inventory (CBDI) was administered to all children and adolescents. After the data quality control process, the study sample was reduced to 4143 children and adolescents. Children and adolescents were divided two groups according to the experience or non-experience of suicide attempts: group 1 (n=80) and group 2 (n=4063), respectively. Three categories of independent variables were assessed: adolescent, family, and socioeconomic characteristics. Logistic regression models were based on the children and adolescents and on parent reports. The prevalence of suicide attempts as reported by the children and adolescents was 1.93% (n=80).The mean age of group 1 was higher than that of group 2 (p=0.002, t=-3.172), as was the mean score of CBDI (p=0.000, t=-9.083). Logistic regression analysis indicated that having problems with parents, using illicit drugs, and psychiatric problems in relatives best predicted suicide attempts in Turkish children and adolescents.     

Clinical evidence for utilization of the A3 adenosine receptor as a target to treat rheumatoid arthritis: data from a phase II clinical trial

OBJECTIVE: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist. METHODS: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients. RESULTS:. Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed. CONCLUSION: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.     

The burden attributable to headache disorders in children and adolescents in Lithuania: estimates from a national schools-based study

BackgroundWe recently showed headache to be common in children (aged 7–11 years) and adolescents (aged 12–17) in Lithuania. Here we provide evidence from the same study of the headache-attributable burden.MethodsFollowing the generic protocol for Lifting The Burden’s global schools-based study, this cross-sectional survey administered self-completed structured questionnaires to pupils within classes in 24 nationally representative schools selected from seven regions of the country. Headache diagnostic questions were based on ICHD-3 beta criteria but for the inclusion of undifferentiated headache (UdH; defined as mild headache with usual duration < 1 h). Burden enquiry was conducted in multiple domains.ResultsQuestionnaires were completed by 2505 pupils (1382 children, 1123 adolescents; participating proportion 67.4%), of whom 1858 reported headache in the preceding year, with mean frequency (±SD) of 3.7 ± 4.5 days/4 weeks and mean duration of 1.6 ± 1.9 h. Mean proportion of time in ictal state, estimated from these, was 0.9% (migraine 1.5%, probable medication-overuse headache [pMOH] 10.9%). Mean intensity on a scale of 1–3 was 1.6 ± 0.6 (mild-to-moderate). Symptomatic medication was consumed on 1.5 ± 2.8 days/4 weeks. Lost school time was 0.5 ± 1.5 days/4 weeks (migraine 0.7 ± 1.5, pMOH 5.0 ± 7.8) based on recall, but about 50% higher for migraine according to actual absences recorded in association with reported headache on the preceding day. More days were reported with limited activity (overall 1.2 ± 2.4, migraine 1.5 ± 2.2, pMOH 8.4 ± 8.5) than lost from school. One in 30 parents (3.3%) missed work at least once in 4 weeks because of their son’s or daughter’s headache. Emotional impact and quality-of-life scores generally reflected other measures of burden, with pMOH causing greatest detriments, followed by migraine and tension-type headache, and UdH least. Burdens were greater in adolescents than children as UdH differentiated into adult headache types.ConclusionsHeadache in children and adolescents in Lithuania is mostly associated with modest symptom burden. However, the consequential burdens, in particular lost school days, are far from negligible for migraine (which is prevalent) and very heavy for pMOH (which, while uncommon in children, becomes four-fold more prevalent in adolescents). These findings are of importance to both health and educational policies in Lithuania.     

Repair of nostril stenosis using a triple flap combination: boomerang, nasolabial, and vestibular rotation flaps

Tissue losses within the nose due to various reasons result in the loss of normal anatomy and function. The external nasal valve area is one of the most important functional components of the nose. The columella, lobule, nostril, and alar region are among the components forming the external nasal valve area. Deformities of the nostrils are among the most frequently observed features that interfere with the functional anatomy of the nose. Malformations of the nostrils often emerge subsequent to cleft lip repairs. Stenoses are a common type of pathology among nostril deformities. In cases where a stenosis has formed, breathing problems and developmental anomalies may occur. In the patient with nostril stenosis presented in this report, there was a serious alar collapse and contracture subsequent to a cleft lip repair. In order to repair the nostril stenosis, a "boomerang flap" was chosen. This boomerang flap was used in combination with a nasolabial flap, a vestibular rotation flap, and a conchal cartilage graft to achieve a satisfactory repair.     

Food Effect Projections via Physiologically Based Pharmacokinetic Modeling: Predictive Case Studies

Food can alter the absorption of orally administered drugs. Biopharmaceutics physiologically based pharmacokinetic (PBPK) modeling offers the possibility to simulate a compound's pharmacokinetics under fasted or fed states. To advance the utility of PBPK modeling, with a view to regulatory impact, we have pooled our experience across 4 pharmaceutical companies to propose a general multistep PBPK workflow leveraging pre-existing clinical data for immediate-release formulations of Biopharmaceutics Classification System I and II compounds. With this strategy, we wish to promote pragmatic PBPK approaches for compounds where absorption is well understood, that is, compounds with moderate-to-high permeability that are not substrates for uptake transporters. Five case studies demonstrate how food effect can be well predicted using appropriately established and validated models. The case studies integrate solubility and dissolution data for initial model development and apply a “middle-out” validation with clinical data in one prandial state. Then, whenever possible, a validation against both fasted and fed state data is recommended before application of the models prospectively for to-be-marketed formulations. Thus, when combined with limited clinical data, PBPK models could be used to simulate outcomes for new doses, formulations, or active pharmaceutical ingredient forms, in lieu of a clinical food-effect study.