Long-term data on children implanted with a short electrode array

Ossification and cochlear malformations are no longer seen as a contra-indication to cochlear implantation. The MED-EL COMBI 40+ short electrode was designed specifically for cases where major ossification has occurred, or where full insertion of an electrode may not be possible due to abnormal structure of the cochlea. This study investigates outcomes of 18 children implanted with the short electrode array. These children were assessed using the EARS test battery pre-operatively and at a number of intervals thereafter. Results show a consistent improvement in time on most tests; these results appear to be independent of aetiology. Data from these children were compared to 18 matched pairs implanted with the standard COMBI 40+ electrode array. The short electrode children do not perform as well as the standard children initially, but do tend to catch-up at later test intervals. Results indicate the benefit of using a short electrode when complete insertion of the standard electrode is not viable.     

Experimental bullous pemphigoid generated in mice with an antigenic epitope of the human hemidesmosomal protein BP230

Bullous pemphigoid (BP) is an IgG-mediated autoimmune blistering disease that targets the hemidesmosomal proteins BP230 and BP180. To investigate the pathogenic role of anti-BP230 antibodies, rabbit polyclonal antibodies were generated against an antigenic sequence of the human BP230 antigen (BPAG 1, 2479-2499), which shows 67% homology in the human and the mouse BP230. Purified IgG from the rabbit anti-serum was transferred subcutaneously into the dorsal skin of neonatal isogeneic CBA/Ca (CBA) mice in a dose of 5 mg (n=7) or 1.2 mg IgG/50 microl (n=16). After 24 h, 1 of the mice injected with 5 mg IgG exhibited blisters, but the dorsal skin of all 7 of them was erythematous, and gentle friction produced a fine persistent wrinkling of the epidermis in 4 mice. The mice injected with 1.2 mg IgG developed less severe symptoms. Immunohistological examinations revealed linear rabbit IgG and mouse C3 depositions along the basement membrane of the perilesional skin and subepidermal blister formation. An intradermal inflammatory reaction (granulocyte infiltration) was also detected. None of these symptoms was seen in mice injected with IgG from a control rabbit anti-serum. These findings demonstrate that antibodies against BP230 can elicit the clinical and immunopathological features of BP in neonatal mice, suggesting that anti-BP230 antibodies may possibly play a pathogenic role in this disease.     

Deletion of XPC leads to lung tumors in mice and is associated with early events in human lung carcinogenesis

Chromosome 3p and 1p deletions are among the most frequent genetic changes in human lung cancer and although candidate tumor suppressor genes have been identified in these regions, no causative correlations have been drawn between deletion or mutation of these and lung carcinogenesis. We identify XPC and Gadd45a as genes within each of these regions involved in lung tumor initiation and progression, respectively. One hundred percent of XPC-/- mice develop multiple spontaneous lung tumors with a minority progressing to non-small cell lung adenocarcinoma, occasionally with metastasis to adjacent lymph nodes. Deletion of Gadd45a alone does not lead to increased lung tumors in mice, but coupled with an XPC deletion, it results in lung tumor progression. Analysis of published data indicated allelic loss of XPC in most human lung tumors and allelic loss of Gadd45a in some human lung and other cancer types. Because DNA repair capacity is compromised in XPC+/- cells, it is possible that the loss of a single XPC allele in the human lung might confer a mutator phenotype. Coupled with cigarette carcinogens, decreased DNA repair would lead to additional mutations in genes such as p53 that are frequent targets in lung cancer.     

Alterations of prenatal morphine exposure in mu-opioid receptor density in hypothalamic nuclei associated with sexual behavior

Our previous work demonstrated that prenatal morphine exposure twice daily during gestational days 11-18 differentially alters male and female sexual behavior. One possible explanation may be that prenatal morphine exposure alters the sexual behavior via alterations of mu-opioid receptors in brain regions involved in reproductive function and behavior, including the ventromedial nucleus of the hypothalamus (VMH), arcuate nucleus (ARC), and medial preoptic area (mPOA). In experiment 1, mu-opioid receptor density was analyzed in three groups of adult male rats: gonadally intact, gonadectomized (GNX), and GNX and testosterone 17beta-propionate-treated (TP). In experiment 2, mu-opioid receptor density was analyzed in four groups of adult female rats: ovariectomized (OVX), OVX and estradiol benzoate-treated (EB), OVX and progesterone-treated (P), and OVX and EB- and P-treated (EB+P). Experiment 1 demonstrated that prenatal morphine exposure lowered the mu-opioid receptor density in the mPOA of adult, gonadally intact and in TP males, while this difference was not apparent in GNX male rats. Experiment 2 demonstrated that prenatal morphine exposure increased mu-opioid receptor density in OVX females, while decreasing it in EB females in the VMH. When compared to our previous sexual behavior data, the present results demonstrate that at least some changes in sexual behavior of adult male and female rats prenatally exposed to morphine may be related to alterations in mu-opioid receptors in brain regions controlling sexual behavior.     

Development of the Childhood Atopic Dermatitis Impact Scale: initial validation of a quality-of-life measure for young children with atopic dermatitis and their families

To measure the effects of atopic dermatitis (AD) on the quality of life of affected young children and their families, we developed a prototype 62-item instrument, the Childhood Atopic Dermatitis Impact Scale (CADIS). The prototype CADIS was developed from a comprehensive conceptual framework based on data from parents and clinicians. The instrument had eight subscales (four each for child and parent): physical health, emotional health, physical functioning, and social functioning. The goal of this work was to test the validity of and to refine the prototype of CADIS. Two hundred seventy parents of children under the age of 6 y with AD responded to the instrument. Content validity was demonstrated by expert and parent reviews of the drafted and refined instrument, and by analyzing parents' responses to open-ended questions about their children's skin disease. Construct validity was assessed in exploratory factor analyses which supported a refinement in the conceptual framework to consist of two dimensions with five domains: child dimensions (symptoms and activity limitation/behavior), and parent dimensions (family/social function, sleep, and emotions). Seventeen items were eliminated, yielding a 45-item refined version of CADIS (score 0-180) with evidence of content and construct validity and suggested use in clinical research.     

Supplementary sensory-motor seizures--symptomatology, etiology, and surgical management with illustrative case reports

In the past decade, owing to the advance of epilepsy surgery, growing knowledge has accumulated on the role of the supplementary motor area, described by Penfield and coworkers in the early fifties, in movement regulation and on the characteristics of seizures involving this area. In the Hungarian neurological literature this topic--despite its neurophysiological and practical clinical importance--has been hardly touched. The authors, based on their own experience obtained from surgeries performed within the framework of the "Co-operative Epilepsy Surgery Program", describe the electrophysiological features of this area, its role in movement regulation and the symptoms of epileptic seizures stemmed from or spread onto this area. Using cases as illustrations, they demonstrate the reasoning and various algorithms of the multidisciplinary examination necessary to explore the seizure onset zone and the pathways of seizure spread. Details of the surgical solution are also described.     

Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature

Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal.