Two distinct regions in 2q24.2-q24.3 associated with idiopathic epilepsy

P>Approximately 50% of all carriers of 2q21-q31 deletions present epileptic seizures. The band 2q24 constitutes the smallest commonly deleted segment in these patients, and contains the voltage-gated sodium channel genes SCN1A and SCN2A, associated with Dravet syndrome and benign familial neonatal-infantile seizures, respectively. A further putative locus involving epilepsy in the region was previously identified through disruption of the SLC4A10 gene by translocation. In the course of performing high-resolution DNA copy number analyses on syndromic mentally impaired individuals, we encountered three patients with overlapping deletions in chromosome region 2q24. Two of these patients exhibited epileptic seizures in addition to mental deficiency. The deletion in one of the epileptic patients did not include the SCN cluster, demonstrating that a less severe form of epilepsy maps to an adjacent genomic region. This second region comprises about 3 Mb and contains the candidate gene SLC4A10, providing further support for the potential role of this gene in epilepsy.

Two-stage laparoscopic liver resection for bilateral colorectal liver metastasis

Hepatectomy may prolong the survival of colorectal cancer patients with liver metastases. Two-stage liver surgery is a valid option for the treatment of bilobar colorectal liver metastasis. This video demonstrates technical aspects of a two-stage pure laparoscopic hepatectomy for bilateral liver metastasis. To the authors` knowledge, this is the first description of a two-stage laparoscopic liver resection in the English literature. A 54-year-old man with right colon cancer and synchronous bilobar colorectal liver metastasis underwent laparoscopic right colon resection followed by oxaliplatin-based chemotherapy. The patient then was referred for surgical treatment of liver metastasis. Liver volumetry showed a small left liver remnant. Surgical planning was for a totally laparoscopic two-stage liver resection. The first stage involved laparoscopic resection of segment 3 and ligature of the right portal vein. The postoperative pathology showed high-grade liver steatosis. After 4 weeks, the left liver had regenerated, and volumetry of left liver was 43%. The second stage involved laparoscopic right hepatectomy using the intrahepatic Glissonian approach. Intrahepatic access to the main right Glissonian pedicle was achieved with two small incisions, and an endoscopic vascular stapling device was inserted between these incisions and fired. The line of liver transection was marked following the ischemic area. Liver transection was accomplished with the Harmonic scalpel and an endoscopic stapling device. The specimen was extracted through a suprapubic incision. The falciform ligament was fixed to maintain the left liver in its original anatomic position, avoiding hepatic vein kinking and outflow syndrome. The operative time was 90 min for stage 1 and 240 min for stage 2 of the procedure. The recoveries after the first and second operations were uneventful, and the patient was discharged on postoperative days 2 and 7, respectively. Two-stage liver resections can be performed safely using laparoscopy. The intrahepatic Glissonian approach is a useful tool for pedicle control of the right liver, especially after previous dissection of the hilar plate.

Age-dependent increase in blood pressure in two different Native American communities in Brazil

Objective Cardiovascular risk factors were surveyed in two Indian populations (Guarani, n=60; Tupinikin, n=496) and in a non-Indian group (n=114) living in the same reserve in southeast Brazilian coast. The relationship between an age-dependent blood pressure (BP) increase with salt consumption was also investigated. Methods Overnight (12 h) urine was collected to evaluate Na excretion. Fasting glucose and lipids, anthropometry, BP, ECG and carotid-femoral pulse wave velocity (PWV) were measured in a clinic visit. Participation (318 men/352 women, age 20-94 years; mean=37.6 +/- 14.9 years) comprised 80% of the eligible population. Results The prevalence of hypertension, diabetes and high cholesterol was similar in Tupinikins and in non-Indians and higher than in Guaranis. The prevalence of smoking and obesity was higher in the latter group. Hypertension and diabetes were detected in only one individual of the Guarani group. Mean BP adjusted to age and BMI was significantly lower (P<0.01) in Guaranis (82.8 +/- 1.6 mmHg) than in Tupinikins (92.3 +/- 0.5 mmHg) and non-Indians (91.6 +/- 1.1 mmHg). Urinary Na excretion (mEq/12h), however, was similar in the three groups (Guarani=94 +/- 40; Tupinikin=105 +/- 56; non-Indian=109 +/- 55; P>0.05). PWV (m/s) was lower (P<0.01) in Guarani (7.5 +/- 1.4) than in Tupinikins (8.8 +/- 2.2) and non-Indians (8.4 +/- 2.0). Multiple regression analysis showed that age and waist-to-hip ratio (WHR) were independent predictors of SBP and DBP (r(2)=0.44) in Tupinikins, whereas the WHR was the unique independent predictor of BP variability in Guaranis (r(2)=0.22). Conclusion Lower BP levels in Guaranis cannot be explained by low salt intake observed in other primitive populations. J Hypertens 27:1753-1760 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

The influence of the amount of sunscreen applied and its sun protection factor (SPF): evaluation of two sunscreens including the same ingredients at different concentrations

Background To estimate labeled sun protection factor (SPF) for sunscreen, the amount of product applied on volunteers, according to food and drug administration (FDA) and International protocols, is 2 mg/cm(2). However, different studies have shown that consumers actually apply much less product when exposed to the sun. Previous studies have reported contradictory findings in an attempt to correlate the amount applied in relation to SPF. The objective of the present study was to estimate the influence of the quantity of sunscreen applied in the determination of SPF, according to the FDA methodology. Subjects and methods Forty volunteers were included in two groups (SPF 15 and 30). The selected sunscreen was then applied in four different quantities (2, 1.5, 1.0 and 0.5 mg/cm(2)). All areas were irradiated with a solar simulator. After 24 h, the minimal erythemal dose (MED) and SPF were determined. Results In both groups, we observed that the SPF decreased when the amount of sunscreen applied was decreased. The differences between the 2 mg/cm(2) area and the others were significant in both groups (P < 0.001). The correlation between specified SPF and applied amount grew exponentially. Conclusion The protection provided by sunscreen is related to the amount of product applied. It is essential to educate consumers to apply larger amounts of sunscreen for adequate photoprotection.

Performance of Two Commercial ELISAs for Detecting IgA Anti-Human and Anti-Guinea Pig Tissue Transglutaminase Antibodies

Background: Sensitivity and specificity of anti-human tissue transglutaminase antibodies (anti-htTGA) seem to be superior to those of anti-tissue transglutaminase of guinea pig (anti-gptTGA) for screening patients with celiac disease (CD), but there are still controversies. The aim of this study was to evaluate the performance of two INOVA ELISA kits to detect IgA anti-htTGA and anti-gptTGA in patients with and without CD. Methods: The study groups were comprised of 49 anti-endomysial antibody (EMA)-positive untreated-CD, and 123 controls (EMA-negative treated CD, EMA-negative chronic diarrhea, autoimmune hepatitis, inflammatory bowel disease and healthy people). Results: The agreement between the two ELISAs was statistically significant in all study groups and there was no significant difference between them (92.7% agreement; kappa=0.70; kappa p=0.001; McNemar p=1). All patients with serum reactivity of more than 100 units had histologic diagnosis of CD. In seven of 10 patients with treated-CD who had control biopsies, villous atrophy was still present in four who tested positive by both kits. Two of three celiacs with histologic remission tested positive for both anti-tTGA. Conclusions: the anti-gptTGA and anti-htTGA determination were equally efficient in identifying patients with untreated-CD with high titers of EMA. Whatever the anti-tTGA ELISA used, the reactivity above 100 units was always related to active CD diagnosed by histologic alterations in intestinal biopsies. The anti-tTGA reactivity by both kits was not only similar in determining histologic activity in the follow-up of CD after a gluten free diet, but also in identifying positive sera from the control groups, regardless if CD has been confirmed by duodenal biopsies. (Clin. Lab. 2010;56:29-35)

Wilson`s disease: two treatment modalities. Correlations to pretreatment and posttreatment brain MRI

Brain magnetic resonance imaging (MRI) studies on Wilson`s disease (WD) show lack of correlations between neurological and neuroimaging features. Long-term follow-up reports with sequential brain MRI in patients with neurological WD comparing different modalities of treatment are scarce. Eighteen patients with neurological WD underwent pretreatment and posttreatment brain MRI scans to evaluate the range of abnormalities and the evolution along these different periods. All patients underwent at least two MRI scans at different intervals, up to 11 years after the beginning of treatment. MRI findings were correlated with clinical picture, clinical severity, duration of neurological symptoms, and treatment with two different drugs. Patients were divided into two groups according to treatment: d-penicillamine (D-P), zinc (Zn), and Zn after the onset of severe intolerance to D-P. MRI scans before treatment showed, in all patients, hypersignal intensity lesions on T2- and proton-density-weighted images bilaterally and symmetrically at basal nuclei, thalamus, brain stem, cerebellum, brain cortex, and brain white matter. The most common neurological symptoms were: dysarthria, parkinsonism, dystonia, tremor, psychiatric disturbances, dysphagia, risus sardonicus, ataxia, chorea, and athetosis. From the neurological point of view, there was no difference on the evolution between the group treated exclusively with D-P and the one treated with Zn. Analysis of MRI scans with longer intervals after the beginning of treatment depicted a trend for neuroimaging worsening, without neurological correspondence, among patients treated with Zn. Neuroimaging pattern of evolution was more favorable for the group that received exclusively D-P.

Two-Year Outcome of Partial Lacrimal Punctal Occlusion in the Management of Dry Eye Related to Sjogren Syndrome

Purpose: To analyze the influence of thermal partial punctal occlusion on the ocular surface of dry eye related to Sjogren syndrome. Material and Methods: Thirty-seven eyes of 19 patients (3 male and 16 female; 49.11 +/- 14.33 years old) with keratoconjunctivitis sicca were enrolled in this study. Superior and inferior partial occlusion were performed in both eyes under topical anesthesia using thermal cautery with a sterile tip to obtain lacrimal punctum smaller than 0.5 mm. Schirmer I, break-up-time, diameter of lacrimal puncta, corneal fluorescein, and rose Bengal staining scores were analyzed before and after 24 weeks and after 24 months of the procedure. All measurements were performed under controlled climate. Results: The average lacrimal punctum diameter before the procedure was 0.65 +/- 0.134 mm. All lacrimal puncta were successfully reduced to less than 0.5 mm after 4 weeks of the procedure. The average Schirmer I test values improved statistically after 24 weeks and maintained stable after 24 months. Average break-up-time, rose Bengal, and fluorescein staining score values improved statistically after 24 weeks and improved even more after 24 months. Average Schirmer I test, break-up-time, rose Bengal, and fluorescein staining scores showed significant improvement (p < 0.0001) after 24 months of partial thermal punctal occlusion. Conclusion: Our study showed that reducing the punctum diameter to 0.5 mm can improve vital staining scores, break-up-time, and Schirmer I test in dry eye related to Sjogren syndrome.

Two-stage transvaginal cervical length screening for preterm birth in twin pregnancies

Aim: To compare cervical length (CL) at 18-21 and 22-25 weeks` gestation in twin pregnancies in prediction of spontaneous preterm delivery and to examine cervical shortening. Methods: Retrospective cohort study of CL measured at 18-21 and 22-25 weeks` gestation in twin pregnancies. Results: Receiver operating characteristics (ROC) curve revealed area of 0.64 (95% CI 0.53-0.75) and 0.80 (95% CI 0.72-0.88) for measurements at 18-21 and 22-25 weeks, respectively (P <= 0.001). Sensitivities of 33.3% and 23% and negative predicting value (NPV) of 97.3% and 86.8% for delivery at <28 and <34 weeks gestation were reached for measurements at 18-21 weeks. Sensitivities of 71.4% and 38.2% and NPV of 99.1% and 91.4% for delivery at <28 and <34 weeks` gestation were reached for measurements at 22-25 weeks. Cervical length shortening analysis showed an area under ROC curve of 0.81 (95% CI 0.73-0.89) and best cut-off was at >= 2 mm/week. Sensitivities of 80% and 60.8% and NPV of 98.9% and 90.6% for delivery at <28 and <34 weeks gestation were reached. Conclusions: In twin gestations, assessment of CL at 22-25 weeks is better than assessment at 18-21 weeks to predict preterm delivery before 34 weeks. Cervical shortening at a rate of >= 2 mm/weeks between 18 and 25 weeks gestation was a good predictor of spontaneous preterm birth in this high-risk population.

Prenatal diagnosis of posterior mediastinal lymphangioma by two- and three-dimensional ultrasonography

Lymphangioma is a rare benign tumor characterized by proliferating lymph vessels and composed of large cyst spaces with endothelium-lined channels of varying dimensions. The incidence of lymphangioma is approximately one in 6000 pregnancies. Less than 1 % of lymphangiomas are purely mediastinal. The great majority of cases are of cystic lymphangioma, but very rarely there is a mixed lesion consisting of multiple cysts of dilated capillary and lymph vessels. We report a case of posterior mediastinal lymphangioma diagnosed at 28 weeks` gestation, in which three-dimensional ultrasonography was helpful in determining the precise location of the tumor. A Cesarean section was performed at 39 weeks and the tumor was resected on the 5(th) day postdelivery; histological examination revealed a mixed cystic lymphangioma. Copyright (C) 2008 ISUOG. Published by John Wiley & Sons, Ltd.

FIBRIN GLUE APPLICATION IN MICROVASCULAR ANASTOMOSIS: COMPARATIVE STUDY OF TWO FREE FLAPS SERIES

Background: Since the first experiments with fibrin glue application in microvascular anastomoses in 1977, several studies have reported its benefits on suture reduction and anastomosis decreased time. In spite of that, clinical experience has been limited to two neurosurgical and two replantation case series, all of them with good results. This study was conducted to evaluate the feasibility and the potential benefits of fibrin glue application in free flaps. Methods: We performed 24 free flaps in 24 patients, from March 2005 to June 2006. Twenty were included in this study. They were divided into two groups according to the anastomosis technique: conventional group (n = 7 patients) and fibrin glue group (n = 13 patients). In the conventional group, the anastomosis was performed with interrupted sutures, whereas in the fibrin glue group, they were performed using less sutures and fibrin glue application. Results: The application of fibrin glue cut by half the number of sutures required to complete the anastomoses. The mean arterial and venous anastomotic times in the conventional group were 27.2 and 24.0 minutes, respectively. In the fibrin glue group, they were 13.6 and 12.6 minutes, respectively. All these differences were statistically significant. There was no significant difference of ischemic time between two groups (P = 0.26). The survival rate of the flaps was similar in both groups: 84.6% (11 of 13) in the fibrin glue group and 85.7% (6 of 7) in the conventional group (P = 1.0). Conclusions: Fibrin glue application in free flaps was feasible and allowed us to complete the anastomoses with fewer sutures and less time. The survival rate of the flaps was not adversely affected by the fibrin glue. (C) 2008 Wiley-Liss, Inc. Microsurgery 29:24-28, 2009.

Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

Dual candidemia detected by nested polymerase chain reaction in two critically ill children

The use of improved microbiological procedures associated with molecular techniques has increased the identification of Candida bloodstream infections, even if the isolation of more than one species by culture methods remains uncommon. We report the cases of two children presenting with severe gastrointestinal disorders and other risk factors that contribute to Candida infections. In the first patient, C. albicans DNA was initially detected by a nested-amplification and C. tropicalis was found later during hospitalization, while blood cultures were persistently negative. In the second child, there was amplification of C. albicans and C. glabrata DNA in the same samples, but blood cultures yielded only C. albicans. Both patients received antifungal therapy but had unfavorable outcomes. These two cases illustrate that PCR was more successful than culture methods in detecting Candida in the bloodstream of high risk children, and was also able to detect the presence of more than one species in the same patient that might impact therapy when the fungi are resistant to azole compounds.

A comparison of the symptomatic profile between two consecutive depressive episodes in patients with bipolar disorder type I

Objective: To compare the variability of patterns of depressive symptoms between two consecutive depressive episodes in patients with bipolar disorder type I. Methods: Review of prospectively collected data from 136 subjects of an out-patient bipolar unit from 1997 to 2007. Binomial statistics was used for the analysis of Hamilton Depression Rating Scale (HDRS)-31 items of the first and second episodes, and the correlation of the HDRS-31 item scores of both episodes was determined using the Spearman coefficient. Results: Ten depressive symptoms showed a significant correlation between index and subsequent episodes: psychological anxiety, somatic anxiety, somatic symptoms, diurnal variation, paranoid symptoms, obsessive and compulsive symptoms, hypersomnia, loss of appetite and helplessness. Only four symptoms were stable in both statistical tests: paranoid symptoms, obsessive-compulsive symptoms, loss of appetite and hypersomnia. Conclusions: Paranoid and obsessive-compulsive symptoms, loss of appetite and hypersomnia tended to be found in successive episodes. However, the moderate correlations of the symptoms across two depressive recurrences suggested that clinical presentations in bipolar depression may not be predicted by symptom profiles presented in previous episodes.

Relative Bioavailability of Two Oral Formulations of Risperidone 2 mg: A Single-Dose, Randomized-Sequence, Open-Label, Two-Period Crossover Comparison in Healthy Brazilian Volunteers

Background: Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. Objectives: The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. Methods: This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. Results: A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 18-58 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m [range, 1.56-1.80 m]; and body mass index, 25 [4] kg/m(2) [range, 18-29 kg/m(2)]). For RSP, mean (SD) C(max) values were 12.6 (2.7) and 16.0 (2.3) ng/mL for the test and reference formulations, respectively. For 9-OH-RSP, mean C(max) values were 17.8 (1.3) and 21.0 (1.7) ng/mL for the test and reference formulations. The 90% CIs for the mean test/reference ratios for RSP C(max), AUC(0-120), and AUC(0-infinity) were 74% to 82%, 75% to 85%, and 76% to 85%, respectively, and 83% to 87%, 75% to 79%, and 75% to 78% for 9-OH-RSP. The related adverse events (headache, low back pain, drowsiness, standing hypotension, local postvenipuncture ecchymoses, insomnia, nausea, and vomiting) were transient and mild. Conclusions: This single-dose study found that the test and reference formulations of oral RSP 2 mg did not meet the Brazilian and US regulatory criteria for bioequivalence in these fasting, healthy volunteers. The study formulations appeared to be well tolerated. (Clin Ther 2010;32:2106-2115) (C) 2010 Elsevier HS Journals, Inc.

Ethical Conflicts over the Management of Transsexual Adolescents-Report of Two Cases

Introduction. The diagnosis and the treatment of transsexualism, particularly during adolescence, generate considerable discussion among specialists. Many health and legal professionals have not yet reached a strong consensus on medical treatment for juvenile transsexuals. Hormonal therapy cannot only represent a medical procedure to adjust the somatic sex to the psychological gender, but can also be a reasonable means of preventing some juvenile transsexuals from engaging in undesirable and risky behavior. Aim. To report the cases of two transsexual adolescents who resorted to prostitution to afford hormonal medications when treatment was denied because of age criteria. Results. Hormonal medications were not recommended by the endocrinology staff because specific laws regulating this medical procedure for juvenile transsexuals in Brazil are lacking. In response, these adolescents chose to use illegally obtained sex hormones to treat themselves. Conclusions. We propose ""harm reduction"" as a means of coping with this dilemma in some cases. Baltieri DA, Cortez FCP, and de Andrade AG. Ethical conflicts over the management of transsexual adolescents-report of two cases. J Sex Med 2009;6:3214-3220.