bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal Reference Ranges of Ductus Venosus Doppler Indices in the Period from 14 to 40 Weeks’ Gestation
Authors: Tongprasert Fuanglada , Srisupundit Kasemsri , Luewan Suchaya , Wanapirak Chanane , Tongsong Theera
Published: November 2011

Objective: To construct reference ranges of ductus venosus (DV) Doppler indices in normal singleton pregnancies. Methods: A cross-sectional study was conducted on low-risk singleton pregnancies with accurate gestational age, and normal fetuses were enrolled into the study. Measurements of DV Doppler indices were determined by experienced sonographers. Poor quality images were excluded. Results: A total of 640 fetuses underwent DV measurements, ranging from 13 to 30 for each gestational week. The relationship between gestational age and DV Doppler indices was not linear. The best-fit regression equations are as follows: preload index = (5.061 – 0.4882) × exp (–0.211 × GA) + 0.4882; peak velocity index for veins = (7.498 – 0.5609) × exp (–0.2184 × GA) + 0.5609; pulsatility index for veins = (17.9 – 0.6053) × exp (–0.2512 × GA) + 0.6053; systolic/atrial wave ratio = (300 – 2.124) × exp (–0.3649 × GA) + 2.124. Notably, during the period from 14 to 20 weeks’ gestation, all of the four indices rapidly decreased and they were relatively stable or slightly decreased after that. The nomogram tables for various percentile ranges were constructed. Conclusion: A nomogram for DV Doppler indices for each gestational week during the period from 14 to 40 weeks’ gestation was established. These reference ranges may be a useful non-invasive tool for evaluation of fetal cardiac function.
Vaginal Rugation Rejuvenation (Restoration): A New Surgical Technique for an Acquired Sensation of Wide/Smooth Vagina
Authors: Ostrzenski Adam
Published: November 2011

Background: No paper on vaginal columnar rugation rejuvenation has been published so far. Objectives: To evaluate a new surgical technique of vaginal rugae restoration for the management of an acquired sensation of wide/smooth vagina (ASWSV). Methods: A prospective observational study was conducted. Ten women with ASWSV (group I) were compared to 10 healthy women (control group II). The vaginal rugation rejuvenation (VRR) technique was developed and appraised. The primary outcome measure was to assess VRR applicability. A secondary outcome measure was to evaluate the surgical resolution of symptoms and signs associated with ASWSV and the impact of VRR on female sexual function. Results: In group I, VRR was executed without complications and the surgical resolution of symptoms and signs associated with ASWSV was observed in all subjects. Improved feelings of penile strokes during coitus were also reported by all subjects of study group I. Conclusions:VRR (restoration) was accomplished without increasing the risks of complications. Surgical resolution of symptoms and signs was observed and sexual function improved by 18.75% following VRR in group I. This nonrandomized study precluded us from drawing the conclusion that VRR is a safe and effective operation.
Macroscopic Analysis of Human Masseter Compartments Assessed by Magnetic Resonance Imaging
Authors: Cioffi Iacopo , Gallo Luigi Maria , Palla Sandro , Erni Stefan , Farella Mauro
Published: November 2011

The human masseter is divided into compartments by aponeuroses. So far, the qualitative and quantitative features of these compartments and their aponeuroses have been scarcely investigated. This study investigated the three-dimensional compartmentalization of the masseter muscle and tested the hypothesis that aponeurosis content varies systematically across different masseter subportions as well as between genders. The right masseter of 14 healthy participants was scanned by magnetic resonance, and the outlines of muscle and aponeuroses were segmented and rendered in three dimensions by AMIRA software. The internal architecture of the masseter muscle varied markedly across individuals, with respect to the number, shape and location of the compartments delimited by aponeuroses. Aponeuroses were widely represented inside the masseter, amounting to 7.1 ± 2.1% of its volume. The aponeurosis content varied systematically across masseter subvolumes and did not differ between genders after adjusting for body height and weight.
Inhaled Corticosteroid/Long-Acting β2-Agonist Combination Therapy for Asthma: Attitudes of Specialists in Europe
Authors: Bousquet Jean , Winchester Chris , Papi Alberto , Virchow J. Christian , Haughney John , Costa David , Usmani Omar , Bjermer Leif , Price David ,   on behalf of the Global Allergy and Asthma European Network (GA2LEN)
Published: November 2011

Background: As new combinations of inhaled corticosteroids (ICSs) and long-acting β2-agonists (LABAs) become available for the treatment of asthma, it will be important to determine criteria against which they can be evaluated. The aim of this study was to assess which attributes of combination therapy physicians consider most important. Methods: Primary and secondary care asthma specialists (n = 32) were recruited for an expert Delphi process that was performed over three rounds to determine attributes perceived to be important in the selection of combination therapy. A pan-European survey was carried out to assess the attitudes, perceptions and prescribing behaviour of a larger population (n = 1,861) of physicians with a specialist interest in asthma treatment. Results: The expert Delphi panel (response rate 59.4%) agreed that the availability of a range of doses (88% agreement in the final round), the efficacy of the combination (81%) and the safety and tolerability of the therapy (81%) were important attributes of ICS/LABA combination treatment. The potency of the ICS (69%) and the speed of onset of the LABA (69%) were also prioritized. The results of the attitudinal survey (eligibility rate 54.1%) showed that the same factors were considered important in everyday clinical practice. Conclusions: These studies identified which attributes of an ICS/LABA treatment are considered most important by an expert panel and a broader group of physicians; further research is warranted to better understand the influences that drive physician opinions.
Comparison of Microcoaxial with Standard Clear Corneal Incisions in Torsional Handpiece Cataract Surgery
Authors: Park Young-Gun , Chung So-Hyang , Joo Choun-Ki
Published: November 2011

Aim: To evaluate the effect of torsional handpiece incision size on phacodynamics and endothelial cell loss (ECL) in cataract surgery. Design: Prospective, observer-masked study at the Department of Ophthalmology and Visual Science, Catholic University of Korea, Seoul St. Mary’s Hospital, Seoul, Korea. Participants: This study was conducted on 60 eyes of 60 patients who underwent phacoemulsification. Methods: Cataract surgery was performed on 28 eyes using a 0.9-mm micro 45-degree Kelman ABS (aspiration bypass system) tip through a 2.8-mm standard incision, and on 32 eyes using a 0.9-mm mini-flared 45-degree Kelman ABS tip through a 2.2-mm microcoaxial incision. As main outcome measures, intraoperative phacodynamics (cumulative dissipated energy, CDE, and balanced salt solution, BSS, use), central corneal thickness (CCT) and endothelial cell count (ECC) were investigated. Results: The CDE was lower in the microcoaxial incision (2.2-mm) group than in the standard incision (2.8-mm) group (p = 0.038). The ECC loss at 6 months was significantly lower in the microcoaxial incision group than in the standard incision group (p = 0.048). There were no differences in BSS use or CCT between the two groups. Conclusions: Torsional ultrasound phacoemulsification using microcoaxial incision with a mini-flared tip resulted in less energy use and less ECL compared with standard incision with a micro tip.
Primary Mucinous Adenocarcinoma of the Renal Pelvis with Elevated CEA and CA19-9
Authors: Ye Yun-Lin , Bian Jun , Huang Yan-Ping , Guo Yan , Li Zhi-Xun , Deng Chun-Hua , Dai Yu-Ping , Sun Xiang-Zhou
Published: November 2011

Primary adenocarcinoma of the renal pelvis is rarely reported in the literature. Here we present a case of primary mucinous adenocarcinoma of the renal pelvis with elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels. A 56-year-old woman was referred to our center with intermittent fever and left-sided back pain for 1 month. Computed tomography showed bilateral nephrolithiasis, mild right hydronephrosis and left pyonephrosis accompanied with ambiguous soft tissues. A radionucleorenogram showed that the glomerular filtration rate of the left and right kidney was 0 and 79 ml/min, respectively. Left nephrectomy was performed without lymph node dissection. Histopathology revealed mucinous adenocarcinoma and elevated serum CEA and CA19-9 levels were found. She died of multiorgan metastasis after 5 months. A review of the literature is also reported.
Double Unfurled Dartos Flap Technique in the Surgical Treatment of Recurrent Urethrocutaneous Fistulas
Authors: Józsa Tamás , Csízy István , Csiszkó Adrienn , Boros Miklós , Rőszer Tamás , Nyirády Péter
Published: November 2011

Background: The management of recurrent urethrocutaneous fistula (RUCF) is a challenging problem that poses a serious difficulty for the hypospadias surgeon. We report here a novel technique in which a double unfurled dartos subcutaneous flap is utilized in the treatment of patients with RUCF. Methods: We retrospectively reviewed the records of all our patients who underwent surgical treatment of urethrocutaneous fistula with this new operative method after previously failed fistula repair. The main novelty of this technique is the use of two opposite medium thickness flaps, unfurled from the inner surface of the dartos fascia and spread over the fistula and each other so as to cover the urethral suture line completely, and fixed to the surrounding corporal tissue. Results: Eight patients with 11 RUCFs (with localizations varying from subcoronal to penoscrotal fistula opening) underwent surgical correction with the new method. There had previously been at least 3 recurrences in 6 of these patients, and different closure techniques had been used. RUCF diameter was <4 mm in all patients. Surgery was performed at the earliest following a 6-month healing period since the last fistula repair attempt. All of the RUCFs were repaired successfully with the technique. After a follow-up of at least 6 months, none of the 8 patients had developed recurrence of the fistula, and there were no postoperative complications. Conclusion: The double unfurled dartos subcutaneous flap method appears to be a simple and appropriate procedure with which to repair recurrent mid-shaft and proximal urethral fistulas after failed hypospadias repair.
Fetal Surgery for Myelomeningocele: Patient Selection, Perioperative Management and Outcomes
Authors: Danzer Enrico , Adzick N. Scott
Published: November 2011

Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities, including paraplegia, hydrocephalus, Chiari II malformation (CM-II), incontinence, sexual dysfunction, skeletal deformations and mental impairment. MMC was the first nonlethal anomaly to be treated by fetal surgery. Experimental and clinical evidence suggests that the primary cause of the neurologic deficit associated with MMC is not simply incomplete neurulation but rather chronic mechanical injury and amniotic fluid-induced chemical trauma that progressively damages the exposed neural tissue during gestation. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks’ gestation may preserve neurologic function, reverse the hindbrain herniation of the CM-II and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, these studies also demonstrate that fetal surgery is associated with significant maternal and fetal risks. Consequently, further research is warranted to further expand our understanding of the pathophysiology of MMC, to evaluate the long-term impact of in utero intervention and to refine the timing and technique of fetal MMC surgery.
Early Intensive Obstetric and Medical Nutrition Care Is Associated with Decreased Prepregnancy Obesity Impact on Perinatal Outcomes
Authors: Reyes Enrique , Martínez Nayeli , Parra Adalberto , Castillo-Mora Alfredo , Ortega-González Carlos
Published: November 2011

Background/Aims: To compare the gestational weight gain and adverse perinatal outcomes in urban Mexican women with prepregnancy overweight or obesity, under an early intensive obstetric and nutrition program versus women with prepregnancy normal weight. Methods: A cohort of 546 pregnant women with prepregnancy normal weight (n = 201, NW), overweight (n = 171, OW) or obesity (n = 174, OB), ≤13 weeks of gestation and a singleton pregnancy. OW and OB groups were under early intensive obstetric and nutritional care and NW group was under routine prenatal care. Miscarriage, hypertensive disorders, premature rupture of membranes, preterm birth, stillbirth, gestational diabetes mellitus (GDM) and large- or small-for-gestational-age newborns, were compared between groups. Results: Weight gain was smaller in OB than in OW or NW (mean ± SD): 6.1 ± 4.4, 9.5 ± 5.1, 10.3 ± 5.4 kg, respectively (p < 0.001). OB women had the highest frequency of GDM (p < 0.001), lack of spontaneous labor (p < 0.001) and preeclampsia (p < 0.001), but no other between-group differences existed. Conclusion: Early intensive medical-nutrition prenatal care and adequate gestational weight gain may contribute to decreasing most maternal and newborn adverse outcomes associated with prepregnancy overweight or obesity.
Effect of Rearing Temperatures during Embryonic Development on the Phenotypic Sex in Zebrafish (Danio rerio)
Authors: Abozaid H. , Wessels S. , Hörstgen-Schwark G.
Published: November 2011

In zebrafish, Danio rerio, a polygenic pattern of sex determination or a female heterogamety with possible influences of environmental factors is assumed. The present study focuses on the effects of an elevated water temperature (35°C) during the embryonic development on sex determination in zebrafish. Eggs derived from 3 golden females were fertilized by the same mitotic gynogenetic male and exposed to a water temperature of 35°C, applied from 5 to 10 h post fertilization (hpf), from 5 to 24 hpf, and from 5 to 48 hpf, which correspond to the following developmental stages: gastrula, gastrula to segmentation, and gastrula to pharyngula stage, respectively. Hatching and survival rates decreased with increasing exposure to high water temperatures. Reductions in the hatching and survival rates were not responsible for differences in sex ratios. Accordingly, exposition of the fertilized eggs to a high temperature (35°C) leads to an increase of the male proportion from 22.0% in the controls to a balanced sex ratio (48.3, 47.5, and 52.6%) in the gastrula, segmentation, and pharyngula groups, respectively. These results prove the possibility to change the pathway of sexual determination during early embryonic stages in zebrafish by exposure to a high water temperature.
Association of Primary Ovarian Insufficiency with a Specific Human Leukocyte Antigen Haplotype (A*24:02-C*03:03-B*35:01) in Japanese Women
Authors: Ayabe T. , Ishizuka B. , Maruyama T. , Fukami M. , Yoshida R. , Uchida H. , Yoshimura Y. , Nagai T. , Ogata T.
Published: November 2011

Primary ovarian insufficiency (POI) is a heterogeneous condition defined by the triad of oligo/amenorrhea, elevated gonadotropins and estrogen deficiency in women under the age of 40 years. Although autoimmune abnormalities appear to be involved in the development of POI, there are only a few studies with respect to human leukocyte antigen (HLA). The objective of this study was to identify an HLA allele(s) and/or haplotype(s) constituting a susceptibility factor(s) for POI. We examined 83 Japanese women with apparently idiopathic isolated POI. For controls, Japanese HLA reference data registered in the HLA Laboratory were utilized. No significant association was found for a total of 94 alleles for HLA-A, B, C, DRB1, and DQB1 loci, after both stringent Bonferroni correction and less stringent Benjamini- Hochberg (B-H) correction for multiple comparisons. By contrast, of 86 haplotypes identified for MHC class I (HLA-A, B, and C) and 31 haplotypes detected for MHC class II (HLA-DRB1 and DQB1), a single haplotype (A*24:02-C*03:03-B*35:01) remained significant after Bonferroni and B-H corrections (frequency: 4.82% in women with POI and 1.06% in the control data; p = 0.00049). The results imply that a specific HLA haplotype (A*24:02-C*03:03-B*35:01) constitutes a susceptibility factor for apparently isolated POI in Japanese women.
First-Trimester Screening for Trisomy 21 Using Alpha-Fetoprotein
Authors: Bredaki Foteini E. , Wright David , Matos Pedro , Syngelaki Argyro , Nicolaides Kypros H.
Published: November 2011

Objective: To investigate the potential value of adding maternal serum alpha-fetoprotein (AFP) to free β-human chorionic gonadotropin (β-hCG) and PAPP-A and fetal nuchal translucency (NT) thickness in first-trimester screening for trisomy 21. Methods: In this case control study, serum AFP was measured in 100 trisomy 21 and 1,500 euploid pregnancies in which screening for trisomy 21 had been performed by a combination of serum free β-hCG and PAPP-A and fetal NT at 11–13 weeks’ gestation. We examined the effect of adding AFP on the performance of screening by the combined test. Results: In the trisomy 21 pregnancies, the median multiple of the normal median AFP, adjusted for gestational age, maternal weight, racial origin, smoking status and method of conception, was significantly reduced (0.7037, 95% CI: 0.6398–0.7739). Adding AFP to the combined test improved the performance of screening and for a risk cut-off of 1 in 100, the false-positive rate was reduced from 2.8 by 0.4% (95% CI: 0.13–0.77%) without a significant change in detection rate. Conclusions: Inclusion of serum AFP improves the performance of the first-trimester combined test in screening for trisomy 21.
Origins and Breakpoint Analyses of Copy Number Variations: Up Close and Personal
Authors: van Binsbergen E.
Published: November 2011

Array-based methods have enabled the detection of many genomic gains and losses. These are stated as copy number variants (CNVs) and comprise up to 13% of the human genome. Based on their breakpoints and modes of formation CNVs are termed recurrent or nonrecurrent. Recurrent CNVs are flanked by low copy repeats and are of a fixed size. They arise as a result of misalignment during meiosis by a mechanism named nonallelic homologous recombination. Several of such recurrent CNVs have been linked to human diseases. Nonrecurrent CNVs, which are not flanked by low copy repeats, are of variable size and may arise via mechanisms like nonhomologous end joining and replication-based mechanisms described by the fork stalling and template switching and microhomology-mediated break-induced replication models. It is becoming clear that most disease-causing CNVs are nonrecurrent and generally arise via replication-based mechanisms. Furthermore, it is now appreciated that genomic features other than low copy repeats play a role in the formation of nonrecurrent CNVs. This review will discuss the different mechanisms of CNV formation and how high resolution analyses of CNV breakpoints have added to our knowledge of their precise structure.
Endocrinology and Gynecology of Girls and Women with Low Birth Weight
Authors: Ibáñez Lourdes , López-Bermejo Abel , Díaz Marta , Marcos Maria Victoria
Published: November 2011

In girls, low birth weight (LBW), when followed by postnatal catch-up growth, is accompanied by endocrine-metabolic abnormalities which include a more adipose body composition (with increased visceral fat), insulin resistance and a less favorable adipokine profile as early as in the pre-school age. These girls also exhibit follicle-stimulating hormone hypersecretion both in early infancy and early post-menarche, with reduced uterine and ovarian size in adolescence. These endocrine and gynecological changes result in a decreased ovulation rate and in an advanced tempo of adrenarche, pubertal development and menarche (by nearly a year, compared to non-LBW girls). The earlier maturation in LBW girls may result in a loss of about 1 SD in height, as compared with target height. During the post-menarcheal period, LBW girls are at increased risk of developing polycystic ovary syndrome. Early insulin sensitization may prevent or delay some of the endocrine-metabolic abnormalities associated to LBW.
Dose-Dependent Protective Effect of Ivabradine against Ischemia-Reperfusion-Induced Renal Injury in Rats
Authors: Beytur Ali , Binbay Murat , Sarihan M. Ediz , Parlakpinar Hakan , Polat Alaadin , Gunaydin M. Orhun , Acet Ahmet
Published: November 2011

Background/Aims: This study was designed to investigate the dose-dependent protective effect of ivabradine, a specific inhibitor of the cardiac sinoatrial node, on renal ischemia-reperfusion (I/R) injury in rats. Methods: Rats were divided into six groups: group 1, control; group 2, I/R (60 min ischemia followed by 24 h reperfusion); groups 3 and 4, 0.6–6 mg/kg ivabradine; and groups 5 and 6, sham+0.6–6 mg/kg ivabradine. At the end of the study, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase contents were assayed in the kidney tissues; serum blood levels of urea nitrogen (BUN), creatinine (Cr) and albumin also were determined. Results: Tissue MDA levels were found to be significantly higher in the I/R group, whereas SOD and CAT levels were lower when compared to the control group. Ivabradine (0.6 mg/kg) treatment reduced the MDA levels and elevated the SOD and CAT enzyme activity. Treatment with a dose of 6 mg/kg ivabradine further increased MDA levels and did not ameliorate SOD or CAT activities. Serum levels of BUN and Cr were significantly higher in the I/R group. I/R+0.6 mg ivabradine reduced the elevated BUN and Cr levels. Conclusion: This study indicates that ivabradine exerts a dose-dependent response beyond heart rate reduction against renal I/R injury.
The Pseudoautosomal Region and Sex Chromosome Aneuploidies in Domestic Species
Authors: Raudsepp T. , Das P.J. , Avila F. , Chowdhary B.P.
Published: November 2011

The pseudoautosomal region (PAR) is a unique and specialized segment on the mammalian sex chromosomes with known functions in male meiosis and fertility. Detailed molecular studies of the region in human and mouse show dramatic differences between the 2 PARs. Recent mapping efforts in horse, dog/cat, cattle/ruminants, pig and alpaca indicate that the PAR also varies in size and gene content between other species. Given that PAR genes escape X inactivation, these differences might critically affect the genetic consequences, such as embryonic survival and postnatal phenotypes of sex chromosome aneuploidies. The aim of this review is to combine the available information about the organization of the PAR in domestic species with the cytogenetic data on sex chromosome aneuploidies. We show that viable XO individuals are relatively frequently found in species with small PARs, such as horses, humans and mice but are rare or absent in species in which the PAR is substantially larger, like in cattle/ruminants, dogs, pigs, and alpacas. No similar correlation can be detected between the PAR size and the X chromosome trisomy in different species. Recent evidence about the likely involvement of PAR genes in placenta formation, early embryonic development and genomic imprinting are presented.
Generation and Biological Properties of a Recombinant Dodecahedron Containing the Short Fiber Protein of the Human Adenovirus 41
Authors: Siqueira-Silva Joselma , Fenel Daphna , Gout Evelyne , Yeda Fernanda P. , Marinheiro Juliana C. , Barrella Karina M. , Silva Misael L. , Schoehn Guy , Harsi Charlotte M. , Fender Pascal
Published: November 2011

Objective: In order to gain further insight into the function of the enteric adenovirus short fiber (SF), we have constructed a recombinant dodecahedron containing the SF protein of HAdV-41 and the HAdV-3 penton base. Methods: Recombinant baculoviruses expressing the HAdV-41 SF protein and HAdV-3 penton base were cloned and amplified in Sf9 insect cells. Recombinant dodecahedra were expressed by coinfection of High Five™ cells with both baculoviruses, 72 h post-infection. Cell lysate was centrifuged on sucrose density gradient and the purified recombinant dodecahedra were recovered. Results: Analysis by negative staining electron microscopy demonstrated that chimeric dodecahedra made of the HAdV-3 penton base and decorated with the HAdV-41 SF were successfully generated. Next, recombinant dodecahedra were digested with pepsin and analyzed by Western blot. A ‘site-specific’ proteolysis of the HAdV-41 SF was observed, while the HAdV-3 penton base core was completely digested. Conclusion: These results show that, in vitro, the HAdV-41 SF likely undergoes proteolysis in the gastrointestinal tract, its natural environment, which may facilitate the recognition of receptors in intestinal cells. The results obtained in the present study may be the basis for the development of gene therapy vectors towards the intestinal epithelium, as well as orally administered vaccine vectors, but also for the HAdV-41 SF partner identification.
Melamine-Related Urinary Stones in 195 Infants and Young Children: Clinical Features within 2 Years of Follow-Up
Authors: Wen Jian Guo , Chang Qing Long , Lou An Feng , Li Zhen Zhen , Lu Shan , Wang Yan , Wang Ya Lun , Hu Jin Hua , Mao Shu Ping , Zhang Yan , Xue Rui , Ren Chuanchuan , Xing Lu , Zhang Guo Xian , Zhang Shengjun , Djurhuus Jens Christian , Frøkiaer Jørgen
Published: November 2011

Objective: To summarize the clinical features and follow-up, the effects of melamine-tainted milk powder (MMP) consumption on kidney and body growth in children who suffered from melamine-related urinary stones (MUS) 2 years earlier were checked. Measurements: Body height and weight, kidney and bladder morphology monitored by ultrasound, urinalysis and renal function were recorded. Plain abdominal radiography was performed for differential diagnosis. The first follow-up was carried out at 15 months and the second 2 years later for patients who showed any abnormality at the first follow-up. Two hundred age- and gender-matched cohorts were included. Results: All cases received conservative treatment in hospital. Fifteen months of follow-up was successfully carried out in 167 cases. 91 children had residual MUS at the time of discharge, 58 MUS disappeared completely, 25 dissolved partially, 1 increased in size, and 7 did not change. At 2 years of follow-up, the residual stones all disappeared except for 1 case; the patient who showed a delayed development with regard to height caught up at 24 months of follow-up. Conclusions: Conservative treatment shows a high effectiveness in cases with residual MUS. Consumption of MMP with timely treatment did not demonstrate an evident impact on kidney and bladder although body height is slightly affected in a few cases.
Pre- and Postnatal Ultrasound and Magnetic Resonance Imaging of Intracranial Extra-Axial Glioneuronal Heterotopia
Authors: Meoded Avner , Turan Sifa , Harman Chris , Poretti Andrea , Zinreich James , Huisman Thierry A.G.M.
Published: November 2011

Glioneuronal heterotopias are rare malformations composed of differentiated derivates of neuroectodermal tissue that include disorganized neuronal and glial cells. They are typically located extracranially. The nasal cavity represents the most common location. Glioneuronal heterotopias have also been reported in the orbit, pharynx, middle ear, neck and thorax. Rarely, glioneuronal heterotopias may be located intracranially. We are aware of only 15 patients reported with intracranial extra-axial glioneuronal heterotopia (IEGH). We present the prenatal ultrasound and MRI as well as the matching postnatal CT, conventional MRI and diffusion tensor imaging findings of a newborn with an infratentorial IEGH accompanied with craniofacial anomalies.
Mild to Moderate Intellectual Disability and Significant Speech and Language Deficits in Patients with FOXP1 Deletions and Mutations
Authors: Horn D.
Published: November 2011

Very recently, FOXP1 deficiency was shown to result in a phenotype of intellectual disability with significant speech and language impairment. Behavioral abnormalities should be considered as part of the clinical spectrum. Mild craniofacial abnormalities found in half of the described patients expand the clinical spectrum associated with FOXP1 mutations.
Urethral Reconstruction in Patients Suffering from Aphallia: A Reconstructive Challenge
Authors: Bhandari Mahendra , Sinha Rahul Janak , Singh Vishwajeet
Published: November 2011

Objective: To document our experience (at a tertiary health care center) of reconstruction of the urethra in 3 male patients suffering from aphallia and congenital urethrorectal fistula as well as their long-term follow-up. Methods: Extensive single-stage urethroplasty in 3 patients suffering from aphallia was performed. Prior to that, neophallus reconstruction was done in all 3 patients after puberty. In a single stage, we used oral mucosa and pedicled penile skin onlay for anterior urethra reconstruction and groin-based pedicle (Singapore) flap for posterior urethra substitution surgery. The current follow-up is between 2 and 5 years. During the last follow-up, the patients also answered questions from a validated patient-reported outcome measure and quality of life questionnaire. Results: All the 3 patients are voiding well in the standing position with a mean Qmax of 14 ml/s. None of them has any problems related to the neourethra as per their last follow-up. All 3 patients were satisfied with the surgical procedures related to the aphallia correction and stated that the surgery did not interfere with the quality of their lives. Conclusion: Reconstruction of the urethra from pedicled skin flap combined with buccal mucosa graft urethroplasty gives durable and satisfactory long-term results.
Importance of Ambulatory Blood Pressure Monitoring in Adolescent Hypertension
Authors: Pall Denes , Kiss Istvan , Katona Eva
Published: November 2011

There has been a steady increase in the prevalence of adolescent hypertension in recent years. In order to prevent target organ damages, it is important to determine the group of hypertensive adolescents. If repeatedly elevated blood pressure values are observed, with special emphasis on white coat hypertension, which is particularly frequent at this age, ambulatory blood pressure monitoring is highly recommended before pharmacological treatment is started. In addition, performing ambulatory blood pressure monitoring is recommended with target organ damage, resistance to therapy, and suspicion of secondary hypertension. The results of the widely available, simple-to-use device are easy to reproduce.
Sex Chromosomes in Vertebrates: XX/XY against ZZ/ZW
Authors: Zechner U. , Hameister H.
Published: November 2011

It was noted only recently that the mammalian X/Y sex chromosome system originated late in our therian ancestors. The question is, what makes the X/Y sex chromosome system so special that it has replaced the original Z/W sex chromosome system? Two classes of genes are overrepresented on the X chromosome: sex and reproduction genes and brain-related genes. The X chromosome has acquired bursts of young male-biased genes engaged in sex and reproduction which exemplifies the dynamics of sex chromosome evolution. Brain genes are old genes and display the most conserved transcriptome. The new therian X chromosome was formed by fusion of chromosome building blocks already bearing the highest density of brain genes in the ancestral vertebrate karyotype. These building blocks constitute an X chromosome haplotype that undergoes strong selection and benefits both sexes by oscillating between males and females. We believe that this strategy is superior to male-driven Z/W sex chromosome evolution.
Severe Intellectual Disability Associated with Recessive Defects in CNTNAP2 and NRXN1
Authors: Zweier C.
Published: November 2011

While heterozygous variants in CNTNAP2 and NRXN1 are reported as susceptibility factors for neuropsychiatric disorders, homozygous or compound heterozygous defects in either gene were reported as causative for severe neurodevelopmental disorders. This review provides an overview of the clinical aspects in patients with recessive defects in CNTNAP2 and NRXN1.
Challenges of Interpreting Copy Number Variation in Syndromic and Non-Syndromic Congenital Heart Defects
Authors: Breckpot J. , Thienpont B. , Arens Y. , Tranchevent L.C. , Vermeesch J.R. , Moreau Y. , Gewillig M. , Devriendt K.
Published: November 2011

Array comparative genomic hybridization (aCGH) has led to an increased detection of causal chromosomal imbalances in individuals with congenital heart defects (CHD). The introduction of aCGH as a diagnostic tool in a clinical cardiogenetic setting entails numerous challenges. Based on our own experience as well as those of others described in the literature, we outline the state of the art and attempt to answer a number of outstanding questions such as the detection frequency of causal imbalances in different patient populations, the added value of higher-resolution arrays, and the existence of predictive factors in syndromic cases. We introduce a step-by-step approach for clinical interpretation of copy number variants (CNV) detected in CHD, which is primarily based on gene content and overlap with known chromosomal syndromes, rather than on CNV inheritance and size. Based on this algorithm, we have reclassified the detected aberrations in aCGH studies for their causality for syndromic and non-syndromic CHD. From this literature overview, supplemented with own investigations in a cohort of 46 sporadic patients with severe non-syndromic CHD, it seems clear that the frequency of causal CNVs in non-syndromic CHD populations is lower than that in syndromic CNV populations (3.6 vs. 19%). Moreover, causal CNVs in non-syndromic CHD mostly involve imbalances with a moderate effect size and reduced penetrance, whereas the majority of causal imbalances in syndromic CHD consistently affects human development and significantly reduces reproductive fitness.
SNP Array Analysis in Constitutional and Cancer Genome Diagnostics – Copy Number Variants, Genotyping and Quality Control
Authors: de Leeuw N. , Hehir-Kwa J.Y. , Simons A. , Geurts van Kessel A. , Smeets D.F. , Faas B.H.W. , Pfundt R.
Published: November 2011

Array-based comparative genomic hybridization analysis of genomic DNA was first applied in postnatal diagnosis for patients with intellectual disability (ID) and/or congenital anomalies (CA). Genome-wide single-nucleotide polymorphism (SNP) array analysis was subsequently implemented as the first line diagnostic test for ID/CA patients in our laboratory in 2009, because its diagnostic yield is significantly higher than that of routine cytogenetic analysis. In addition to the detection of copy number variations, the genotype information obtained with SNP array analysis enables the detection of stretches of homozygosity and thereby the possible identification of recessive disease genes, mosaic aneuploidy, or uniparental disomy. Patient-parent (trio) information analysis is used to screen for the presence of any form of uniparental disomy in the patient and can determine the parental origin of a de novo copy number variation. Moreover, the outcome of a genotype analysis is used as a final quality control by ruling out potential sample mismatches due to non-paternity or sample mix-up. SNP array analysis is now also used in our laboratory for patients with disorders for which locus heterogeneity is known (homozygosity pre-screening), in prenatal diagnosis in case of structural ultrasound anomalies, and for patients with leukemia. In this report, we summarize our array findings and experiences in the various diagnostic applications and demonstrate the power of a SNP-based array platform for molecular karyotyping, because it not only significantly improves the diagnostic yield in both constitutional and cancer genome diagnostics, but it also enhances the quality of the diagnostic laboratory workflow.
Pseudophakic Cystoid Macular Edema
Authors: Lobo Conceição
Published: November 2011

Cataract surgery is an efficient procedure, and is generally associated with good visual results. Nevertheless, cystoid macular edema (CME) may develop, and this can result in suboptimal postoperative vision. Many factors are considered to contribute to its development, and although the treatment options depend upon the underlying cause of CME, the usual therapeutic approach for prophylaxis and treatment of CME is directed towards blocking the inflammatory mediators. This article provides a review of possible risk factors, pathogeneses, incidence rates, and methods of diagnosis, as well as the current guidelines for managing CME.
Hemodialysis-Induced Alterations in Macular Thickness Measured by Optical Coherence Tomography in Diabetic Patients with End-Stage Renal Disease
Authors: Theodossiadis Panagiotis G. , Theodoropoulou Sofia , Neamonitou Georgia , Grigoropoulos Vlassis , Liarakos Vasilios , Triantou Eleni , Theodossiadis George P. , Vlahakos Demetrios V.
Published: November 2011

Background/Aims: To evaluate changes in macular thickness measured by optical coherence tomography (OCT) during a hemodialysis (HD) session in diabetic patients with end-stage renal disease. Methods: 72 eyes of 36 diabetic patients with and without macular edema were evaluated before and immediately after an HD session. Average and maximum macular thicknesses in the central disk (6 mm in diameter) and total macular volume were measured. Results: In the eyes with diabetic macular edema, maximum macular thickness within the central disk of 6 mm, and mainly in its peripheral parts, was significantly reduced by 31.18 ± 4.18 µm after HD (p < 0.001). Average macular thickness and total macular volume were also significantly reduced (p = 0.003 and 0.015, respectively). In diabetic eyes without edema, maximum macular thickness decreased significantly by 11.21 ± 1.98 µm after HD (p < 0.001), while average macular thickness and total macular volume decreased slightly (p = 0.034, p = 0.043). Best-corrected visual acuity failed to change. We found a significant association of macular thickness changes with osmolality reduction and the presence of macular edema. Conclusion: HD decreases macular thickness in diabetic patients with macular edema, while there exists a less-pronounced effect in diabetic eyes without edema.
CDKL5-Related Disorders: From Clinical Description to Molecular Genetics
Authors: Bahi-Buisson N. , Bienvenu T.
Published: November 2011

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) have been described in girls with Rett-like features and early-onset epileptic encephalopathy including infantile spasms. To date, with more than 80 reported cases, the phenotype of CDKL5-related encephalopathy is better defined. The main features consist of early-onset seizures starting before 5 months of age, severe mental retardation with absent speech and Rett-like features such as hand stereotypies and deceleration of head growth. On the other hand, neuro-vegetative signs and developmental regression are rare in CDKL5 mutation patients. The CDKL5 gene encodes a serine threonine kinase protein which is characterized by a catalytic domain and a long C-terminal extension involved in the regulation of the catalytic activity of CDKL5 and in the sub-nuclear localization of the protein. To our knowledge, more than 70 different point mutations have been described including missense mutations within the catalytic domain, nonsense mutations causing the premature termination of the protein distributed in the entire open reading frame, splice variants, and frameshift mutations. Additionally, CDKL5 mutations have recently been described in 7 males with a more severe epileptic encephalopathy and a worse outcome compared to female patients. Finally, about 23 male and female patients have been identified with gross rearrangements encompassing all or part of the CDKL5 gene, with a phenotype reminiscent of CDKL5-related encephalopathy combined with dysmorphic features. Even if recent data clearly indicate that CDKL5 plays an important role in brain function, the protein remains largely uncharacterized. Phenotype-genotype correlation is additionally hampered by the relatively small number of patients described.
Oxygen Sensing in Retinal Health and Disease
Authors: Lange Clemens A.K. , Bainbridge James W.B.
Published: November 2011

The retina has a uniquely high metabolic demand for oxygen that is normally met by a highly efficient vascular supply. Oxygen plays an essential role in oxidative phosphorylation as an electron acceptor in the mitochondrial respiratory chain in the synthesis of adenosine triphosphate required to support the metabolic demand, including that of the visual cycle. Maintenance of normal retinal function depends on a continuous supply of oxygen and on the capability to detect and respond rapidly to local oxygen deficiency (hypoxia). The functional reserve of oxygen is small and retinal hypoxia can cause neuroretinal dysfunction and degeneration that lead directly to vision loss. Local oxygen sensing mechanisms control adaptive responses that can help protect against ischaemic injury. In the retina, powerful oxygen sensing mechanisms rapidly detect alterations in intracellular oxygen tension and respond with adaptive changes that redress the balance between oxygen supply and demand. These responses include rapid changes in blood flow, protective metabolic adaptations and angiogenesis. In the eye, however, the angiogenic response to hypoxia is typically associated with oedema, haemorrhage and fibrosis that can exacerbate hypoxic neuroretinal injury, causing severe vision loss. This aberrant response is the target of novel therapies including inhibitors of vascular endothelial growth factor. However, non-specific angiostatic agents fail to consider appropriate beneficial adaptive responses to hypoxia, and risk compromising neuroprotective mechanisms. In this review, we discuss the current understanding of retinal oxygenation and oxygen sensing in health and disease, focussing on the central role of hypoxia-inducible transcription factors, and suggest that therapeutic strategies may be improved by considering more targeted interventions.
Cerebral Microbleeds Predict Impending Intracranial Hemorrhage in Infective Endocarditis
Authors: Okazaki Shuhei , Sakaguchi Manabu , Hyun BooHan , Nagano Keiko , Tagaya Masafumi , Sakata Yasushi , Sakaguchi Taichi , Kitagawa Kazuo
Published: November 2011

Background: Cerebral microbleeds (CMBs) detected by T2*-weighted MRI are a potential indicator of hypertension, microvascular disease and hemorrhagic stroke. An association between infective endocarditis (IE) and CMBs has been reported recently, but the clinical significance remains unclear. We hypothesized that CMBs in patients with IE are associated with vascular vulnerabilities such as mycotic aneurysm or pyogenic vasculitis. Methods: We retrospectively reviewed 26 consecutive patients with definite IE who underwent T2*-weighted MRI and were admitted to 2 medical centers in Osaka, Japan, between January 2006 and June 2010. We examined the incidence of symptomatic intracranial hemorrhage (ICH) occurring after initial MRI examination and investigated the association between ICH, CMBs and other clinical characteristics. Results: CMBs were identified in 14 patients (54%), and 72% of CMBs were found in the lobar region. Symptomatic ICH was observed in 8 patients (31%) during the 3-month follow-up period after initial MRI examination. In multiple logistic regression analyses, the presence of preceding ICH [odds ratio (OR) 40.0, 95% confidence interval (CI) 2.5–2,870] and the presence of CMBs (OR 34.0, 95% CI 1.3–17,300) were independent predictors of the development of ICH. Using cutoff values for CMBs of ≧2 and ≧3, the adjusted ORs for ICH increased (OR 42.1, 95% CI 1.9–24,300, and OR 70.1, 95% CI 2.5–105,000, respectively). Conclusions: In addition to prior ICH, the presence of CMBs was a strong predictor of impending ICH in patients with IE. CMBs might represent vascular vulnerability related to IE.
Life-Threatening Hyponatremia and Acute Renal Failure due to Iatrogenic Neonatal Bladder Rupture
Authors: Printza Nikoleta , Ververi Athina , Bandouraki Maria , Vargiami Euthymia , Gidaris Dimos , Papachristou Fotios
Published: November 2011

Neonatal urinary ascites is a rare entity, usually associated with a spontaneous rupture of the bladder with an underlying pathology such as high pressure or wall disruption. Its presentation involves abdominal distension, metabolic derangement and respiratory compromise. We report the case of a male neonate with solitary functioning kidney presented with life-threatening persistent hyponatremia and acute renal failure due to iatrogenic bladder rupture after catheterization. The aim of our report is to raise awareness on the possibility of bladder perforation in neonates even in the absence of technical faults. We discuss the uncommon presentation of our case and highlight the need for early recognition and management of urinary ascites, addressing all subspecialties involved in diagnostic or therapeutic procedures of neonates with urinary abnormalities.
Epilepsy Surgery in Children Compared to Adults
Authors: Hindi-Ling Hila , Kipervasser Svetlana , Neufeld Miri Y. , Andelman Fani , Nagar Sari , Chistik Vladimir , Veshchev Igor , Fried Itzhak , Kramer Uri
Published: November 2011

Aim: The purpose of this study was to compare the frequency of various surgical techniques and surgical outcome between pediatric and adult populations that underwent epilepsy surgery by the same team.Methods: All patients who underwent epilepsy surgery at the Tel Aviv Medical Center between 1997 and 2006 and had been followed up for >2 years were eligible for this study. The majority (90%) of all epilepsy surgeries carried out in Israel were performed in this institution and by a single neurosurgeon. Only patients that underwent video-EEG monitoring as part of the presurgical evaluation were included in the study. Results: A total of 186 patients (131 adults and 55 children) underwent epilepsy surgery in our institute during the study period, and follow-up was available for 177 patients (95%). While the adults underwent significantly more temporal lobe resections (51 vs. 20%, p < 0.0001), the children had significantly more extra-temporal non-lesional resections (18 vs. 1%, p < 0.0001) and hemispherectomies (5 vs. 1%, p = 0.002). Over one half (54%) of all the patients had a postoperative reduction in seizures of >90%, and 72% had a reduction of >50%, with no group difference in surgical success. Among the lesionectomies, the outcome was better for tumors, especially those in the temporal lobe. Only 1% of the patients had a long-term neurological deficit.Conclusions: Children comprised 30% of the epilepsy surgical cases during the study period. Children underwent more non-lesional resections and hemispherectomies, while adults underwent more temporal lobe resections. There was no age-related difference in surgical outcome.