Inherited thrombophilia in pediatric ischemic stroke: an Egyptian study

Pediatric stroke is relatively uncommon, with often subtle clinical presentations. Numerous predisposing risk factors can be both inherited and acquired, including cardiac disease, vascular abnormalities, infectious diseases, collagen tissue diseases, inborn errors of metabolism, anticardiolipin antibody, lupus anticoagulant, deficiencies of protein C, protein S, antithrombin, or plasminogen, and prothrombotic mutations. We explored risk factors, clinical features, and neuroimaging among Egyptian children with ischemic stroke, and estimated the prevalence of inherited thrombophilia. We included 20 children with ischemic stroke, recruited from the Pediatric Neurology Outpatient Clinic (Ain Shams University). Basic clinical evaluations for stroke and genotyping for factor V 1691 G-A (factor V Leiden), prothrombin 20210 G-A mutations, and methylenetetrahydrofolate reductase 677 C-T polymorphisms were performed using real-time polymerase chain reaction, with fluorescent melting curve detection analysis. Ten patients (50%) manifested methylenetetrahydrofolate reductase polymorphisms (six homozygotes and four heterozygotes). Heterozygous factor V Leiden was present in five (25%), whereas prothrombin mutation was present in only one (5%). Five patients (25%) manifested combined prothrombotic abnormalities. Thirteen demonstrated evidence of inherited thrombophilic disorder; 25% manifested more than one mutation. For appropriate risk assessment, even in the presence of overt acquired thrombotic risk factors, physicians should request complete thrombophilia screening for patients with stroke.     

Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial

Background: Several small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists. Objective: The objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. Study Design: This was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. Study Setting: The study setting was outpatient clinics of two large referral centres. Patients: Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21. Interventions: Participants were randomly assigned to granisetron (Kytril?; SmithKline Beecham, Philadelphia, PA, USA) 1?mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks. Main Outcome Measure: Patients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups. Results: Of the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678]?=?4.941, p?=?0.009), obsession (F [2.337, 88.799]?=?4.938, p?=?0.006) and compulsion (F [2.050, 77.899]?=?4.674, p?=?0.012) subscales. By week 8, complete response and remission were achieved by 20 (100%) and 18 (90%) patients in the granisetron group and by 7 (35%) patients in the placebo group (p-value of Fisher's exact test <0.001, risk ratio (RR) [95% CI]?=?3.857 [2.039, 7.297]). There was no significant difference in the tolerability between the two regimens. Conclusion: Granisetron is an efficacious adjunct for the short-term treatment of patients with moderate to severe OCD and is well tolerated. Clinical Trial Registration Number: IRCT201202041556N32.     

A New Face by Combined Surgery for Patients with Complex Dentofacial Deformity

BACKGROUND: This article aims to present and discuss 53 patients who received a new identity because of major changes to the face after treatment with bimaxillary osteotomy, concomitant maxillomalar augmentation, genioplasty, and rhinoplastic procedures for their complex dentofacial skeletal deformity and class 3 malocclusion. METHODS: During a 12-year period (January 1993 to April 2005), more than 500 patients with dentofacial deformities and malocclusions have undergone orthognathic surgery performed by a team consisting of the same plastic surgeons and orthodontists. Among this group, 53 patients (30 women and 23 men) underwent surgery for both aesthetic and functional concerns. The mean patient age was 20.4 years (range, 17-28 years). All the patients were treated with bimaxillary osteotomy, concomitant maxillomalar augmentation, osseous genioplasty, and rhinoplastic procedures in the same session. The patients were followed 12 to 44 months by the plastic surgeon, and at least 1 year by the orthodontist. RESULTS: There was no orthognathic relapse or other major complications requiring reoperation. There was prolonged nerve anesthesia or hypoesthesia that resolved within 6 months for 4 patients (7.5%), a short period of anesthesia or hypoesthesia that resolved within 4 weeks for 11 patients (20.7%), a wide alar base in 3 patients, and a slight deviation of the cartilage septum in 2 patients. CONCLUSION: In one session, five different procedures can be performed without any problem, each of which can produce major changes to the face while maintaining the whole facial harmony. The authors determined that these dramatic positive outcomes for the combined procedure can easily be tolerated and accepted by all their patients. However, the patients have had difficulty with their family or friends accepting their new appearance, and even have had to change their photos on identification cards. This is encouraging for the management of new patients in the future.     

Correlation between proteinuria level and renal morphology with special reference to electron microscopy in kidney donors

The aims of this study were to evaluate whether there is a correlation between protein level in urine and renal morphology in kidney transplant donors, as well as to detect the role of electron microscopy. For this purpose, kidney biopsies of 10 donors with urine protein levels were evaluated. Seven patients were female and three were male. Two had physiologic proteinuria (< 150 mg/24h), four had non-significant proteinuria (150-300 mg/24h), and three had significant (> 300 mg/24h) proteinuria. Serum creatinine levels were in normal ranges in all patients except for one who had a slight increase (1.76 mg/dL). Seven cases were reported to have normal or nonspecific light microscopic findings. Two of those seven cases had physiologic proteinuria, three had non-significant proteinuria, and two had significant proteinuria. One case had IgA nephropathy with significant proteinuria. One donor had early stage focal segmental glomerulosclerosis with non-significant proteinuria, and one donor had focal interstitial fibrosis with normal urine protein level. There was no statistically significant difference between score means of ultrastructural morphology of the six patients with same patients' light microscopic results and score means of light microscopic results with urine protein levels of all patients. However, there was a significant difference between score means of ultrastructural morphology with urine protein levels of those six patients. In conclusion, urine protein levels and light microscopic findings did not always reflect the detailed morphology alone and together. Therefore, combining with electron microscopic examination could be more beneficial in relieving problems occurring in long-term prognoses.     

Sitimagene ceradenovec, a gene therapeutic for the treatment of glioma

Ark Therapeutics Group plc is developing sitimagene ceradenovec, a herpes simplex virus thymidine kinase/ganciclovir gene therapy utilizing an adenoviral vector, for the potential treatment of glioma. Sitimagene ceradenovec is currently undergoing a phase III clinical trial in malignant glioma patients.     

A novel mutation of 5α-steroid reductase 2 deficiency (CD 65 ALA-PRO) with severe virilization defect in a Turkish family and difficulty in gender assignment

Molecular genetic characterization of mutations in SRD5A2 gene is used as an essential procedure for the final diagnosis of 5α-reductase deficiency. Here, we report a novel homozygous point mutation of SRD5A2 gene at codon 65 in exon 1, due to a proline for alanine substitution in a Turkish family whose proband has severe undervirilization. This mutation has not been reported up to date in association with 5α-reductase deficiency in various ethnic groups. We discussed some questions about gender assignment in addition to the molecular and clinical characteristics of the disease.