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Item does not contain fulltext Pathogenic mutations in TMPRSS3, which encodes a transmembrane serine protease, cause non-syndromic deafness DFNB8/10. Missense mutations map in the low density-lipoprotein receptor A (LDLRA), scavenger-receptor cysteine-rich (SRCR), and protease domains of the protein, indicating that all domains are important for its function. TMPRSS3 undergoes proteolytic cleavage and activates the ENaC sodium channel in a Xenopus oocyte model system. To assess the importance of this gene in non-syndromic childhood or congenital deafness in Turkey, we screened for mutations affected members of 25 unrelated Turkish families. The three families with the highest LOD score for linkage to chromosome 21q22.3 were shown to harbor P404L, R216L, or Q398X mutations, suggesting that mutations in TMPRSS3 are a considerable contributor to non-syndromic deafness in the Turkish population. The mutant TMPRSS3 harboring the novel R216L missense mutation within the predicted cleavage site of the protein fails to undergo proteolytic cleavage and is unable to activate ENaC, thus providing evidence that pre-cleavage of TMPRSS3 is mandatory for normal function.

Contains fulltext : 69893.pdf (Publisher’s version ) (Closed access) In patients with autosomal-recessive retinitis pigmentosa (arRP), homozygosity mapping was performed for detection of regions harboring genes that might be causative for RP. In one affected sib pair, a shared homozygous region of 5.0 Mb was identified on chromosome 6, within the RP25 locus. One of the genes residing in this interval was the retina-expressed gene EGFL11. Several genes resembling EGFL11 were predicted just centromeric of EGFL11. Extensive long-range RT-PCR, combined with 5'- and 3'- RACE analysis, resulted in the identification of a 10-kb transcript, starting with the annotated exons of EGFL11 and spanning 44 exons and 2 Mb of genomic DNA. The transcript is predicted to encode a 3165-aa extracellular protein containing 28 EGF-like and five laminin A G-like domains. Interestingly, the second part of the protein was found to be the human ortholog of Drosophila eyes shut (eys), also known as spacemaker, a protein essential for photoreceptor morphology. Mutation analysis in the sib pair homozygous at RP25 revealed a nonsense mutation (p.Tyr3156X) segregating with RP. The same mutation was identified homozygously in three arRP siblings of an unrelated family. A frame-shift mutation (pPro2238ProfsX16) was found in an isolated RP patient. In conclusion, we identified a gene, coined eyes shut homolog (EYS), consisting of EGFL11 and the human ortholog of Drosophila eys, which is mutated in patients with arRP. With a size of 2 Mb, it is one of the largest human genes, and it is by far the largest retinal dystrophy gene. The discovery of EYS might shed light on a critical component of photoreceptor morphogenesis.

Contains fulltext : 70189.pdf (Publisher’s version ) (Closed access) Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

Contains fulltext : 70666.pdf (Publisher’s version ) (Closed access) Peripherin/rds is an integral membrane glycoprotein, mainly located in the rod and cone outer segments. The relevance of this protein to photoreceptor outer segment morphology was first demonstrated in retinal degeneration slow (rds) mice. Thus far, over 90 human peripherin/RDS gene mutations have been identified. These mutations have been associated with a variety of retinal dystrophies, in which there is a remarkable inter- and intrafamilial variation of the retinal phenotype. In this paper, we discuss the characteristics of the peripherin/RDS gene and its protein product. An overview is presented of the broad spectrum of clinical phenotypes caused by human peripherin/RDS gene mutations, ranging from various macular dystrophies to widespread forms of retinal dystrophy such as retinitis pigmentosa. Finally, we review the proposed genotype-phenotype correlation and the pathophysiologic mechanisms underlying this group of retinal dystrophies.

Purpose Dominant cystoid macular degeneration (DCMD) is an autosomal dominant trait of cystoid macular edema with poor visual prognosis. Until now, no efficient treatments for DCMD have been reported. The authors evaluated a somatostatin-analogue (octreotide acetate) as treatment for DCMD. Methods The authors treated four patients with early DCMD by intramuscular longacting octreotide acetate, 20 mg every 4 weeks for 1 year. In addition to general ophthalmologic examination the authors performed fluorescein angiography (FA) before and after treatment. Results Seven out of eight eyes showed improvement on FA and stabilization of visual acuity. Conclusions Somatostatin-analogues may reduce cystoid edema in DCMD and may thus prevent disease-related visual loss.

Contains fulltext : 69050.pdf (Publisher’s version ) (Open Access) Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS: MIM 270550) is a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy. This disorder, considered to be rare, was first described in the late seventies among French Canadians in the isolated Charlevoix-Saguenay region of Quebec. Nowadays, it is known that the disorder is not only limited to this region but occurs worldwide. Our objective was to identify cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) in Dutch patients with recessive early-onset cerebellar ataxia by sequencing the complete SACS gene. In a Dutch cohort of 43 index patients with ataxia onset before age 25, we identified 16 index patients (total 23 patients) with mutations in the SACS gene. Nine of them had homozygous mutations, and seven of them had compound heterozygous mutations. Retrospectively, the phenotype of patients carrying mutations was remarkably uniform: cerebellar ataxia with onset before age 13 years, lower limb spasticity and sensorimotor axonal neuropathy, and cerebellar (vermis) atrophy on magnetic resonance imaging, consistent with the core ARSACS phenotype previously described. The high rate of mutations (37%) identified in this cohort of Dutch patients suggests that ARSACS is substantially more frequent than previously estimated. We predict that the availability of SACS mutation analysis as well as an increasing awareness of the characteristic ARSACS phenotype will lead to the diagnosis of many additional patients, possibly even at a younger age.

Contains fulltext : 70417.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To study the audiologic outcome of bone-anchored hearing aid (BAHA) application in patients with congenital unilateral conductive hearing impairment. STUDY DESIGN: Prospective audiometric evaluation on 20 patients. SETTING: Tertiary referral center. PATIENTS: The experimental group comprised 20 consecutive patients with congenital unilateral conductive hearing impairment, with a mean air-bone gap of 50 dB. METHODS: Aided and unaided hearing was assessed using sound localization and speech recognition-in-noise tests. RESULTS: Aided hearing thresholds and aided speech perception thresholds were measured to verify the effect of the BAHA system on the hearing acuity. All patients fulfilled the criteria that the aided speech reception thresholds or the mean aided sound field thresholds were 25 dB or better in the aided situation. Most patients were still using the BAHA almost every day. Sound localization scores varied widely in the unaided and aided situations. Many patients showed unexpectedly good unaided performance. However, nonsignificant improvements of 3.0 (500 Hz) and 6.9 degrees (3,000 Hz) were observed in favor of the BAHA. Speech recognition in noise with spatially separated speech and noise sources also improved after BAHA implantation, but not significantly. CONCLUSION: Some patients with congenital unilateral conductive hearing impairment had such good directional hearing and speech-in-noise scores in the unaided situation that no overall significant improvement occurred after BAHA fitting in our setup. Of the 18 patients with a complete data set, 6 did not show any significant improvement at all. However, compliance with BAHA use in this patient group was remarkably high. Observations of consistent use of the device are highly suggestive of patient benefit. Further research is recommended to get more insight into these findings.

Contains fulltext : 70855.pdf (Publisher’s version ) (Closed access) Meckel-Gruber syndrome (MKS) is an autosomal recessive, lethal multisystemic disorder characterized by meningooccipital encephalocele, cystic kidney dysplasia, hepatobiliary ductal plate malformation, and postaxial polydactyly. Recently, genes for MKS1 and MKS3 were identified, putting MKS on the list of ciliary disorders (ciliopathies). By positional cloning in a distantly related multiplex family, we mapped a novel locus for MKS to a 3-Mb interval on 12q21. Sequencing of the CEP290 gene located in the minimal critical region showed a homozygous 1-bp deletion supposed to lead to loss of function of the encoded centrosomal protein CEP290/nephrocystin-6. CEP290 is thought to be involved in chromosome segregation and localizes to cilia, centrosomes, and the nucleus. Subsequent analysis of another consanguineous multiplex family revealed homozygous haplotypes and the same frameshift mutation. Our findings add to the increasing body of evidence that ciliopathies can cause a broad spectrum of disease phenotypes, and pleiotropic effects of CEP290 mutations range from single organ involvement with isolated Leber congenital amaurosis to Joubert syndrome and lethal early embryonic multisystemic malformations in Meckel-Gruber syndrome. We compiled clinical and genetic data of all patients with CEP290 mutations described so far. No clear-cut genotype-phenotype correlations were apparent as almost all mutations are nonsense, frameshift, or splice-site changes and scattered throughout the gene irrespective of the patients' phenotypes. Conclusively, other factors than the type and location of CEP290 mutations may underlie phenotypic variability.

Contains fulltext : 70980.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Evaluation of the management and survival of patients treated for temporal bone squamous cell carcinoma. STUDY DESIGN: A retrospective analysis. SETTING: Tertiary care, academic referral center. PATIENTS: Twenty-eight patients underwent primary treatment for squamous cell carcinoma of the temporal bone. INTERVENTIONS: The patients were staged using the modified Pittsburgh staging system. Patients underwent a local resection, lateral temporal bone resection, or a subtotal lateral temporal bone resection usually followed by radiotherapy. MAIN OUTCOME MEASURE: The survival rate of patients grouped by tumor size was calculated. RESULTS: Staging revealed 12 pT1, 2 pT2, 4 pT3, and 10 pT4 tumors. The mean follow-up was 34 months (2-132 mo). The Kaplan-Meier survival curves showed survival rates at 5 years of 83 and 25% for the stages pT1 and pT4, respectively. The pooled survival curves showed survival rates at 5 years of 85 and 46% for the stages pT1p/T2 and pT3/pT4, respectively. CONCLUSION: Long-term prognosis of the carcinoma of the external auditory canal mainly depends on the stage and primary treatment. Surgery may consist of a lateral temporal bone or subtotal temporal bone resection; in T3 and T4 tumors, resection may be combined with a superficial parotidectomy. If disease is diagnosed in the neck or parotid, then a neck dissection and total parotidectomy may also be performed. Additional radiotherapy should be provided in incompletely resected T1 and all T2 and T3 tumors and part of the T4 tumors. T4 tumors may be treated according to their subclassification based on the anatomic extension.

Contains fulltext : 71383.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To evaluate the preliminary visual results of femtosecond laser-assisted Descemet stripping endothelial keratoplasty (FS-DSEK). METHODS: We prospectively analyzed results of 20 consecutive patients with Fuchs endothelial dystrophy or aphakic/pseudophakic bullous keratopathy who underwent FS-DSEK. Best spectacle-corrected visual acuity (BSCVA), refraction, corneal topography, and endothelial cell density were measured preoperatively and 3 and 6 months after FS-DSEK. Corneal thickness was measured using an optical coherence tomography technique. RESULTS: The average BSCVA of 11 eyes with normal visual potential significantly improved from 20/110 +/- 4 lines to 20/57 +/- 1 line at 6 months (P < .007). At 6 months, the mean (SD) hyperopic shift was 2.24 (2.3) diopters (D). Preoperative and 6 months postoperative refractive astigmatism were -0.75 (0.9) D and -1.58 (1.1) D (P = .01), but the topographic astigmatism did not change postoperatively (P = .95). Mean (SD) endothelial cell density at 6 months was 1368 (425) cells/mm(2). There was a persistent deswelling of the graft up to 3 months postoperatively. Complications included graft dislocations requiring repositioning (20%), pupillary block glaucoma (5%), epithelial ingrowth (5%), and primary graft failure (5%). CONCLUSIONS: Femtosecond laser-assisted Descemet stripping endothelial keratoplasty was effective in treating endothelial failure with minimal induced refractive astigmatism, limited improvement of BSCVA, and induction of a hyperopic shift. Endothelial cell count and dislocation rate were significant, which may be related to the surgical technique.

Contains fulltext : 69544.pdf (Publisher’s version ) (Closed access) Developmental disorders might differ in their language profiles when using parent reports. The first study indicated that school aged children with ASD have similar language profiles as children with ADHD. Both groups had relatively more difficulties with pragmatics than with structural language aspects. The second study indicated that both preschoolers with ASD and those with SLI show the opposite pattern, thus having relatively more difficulties with structural language aspects than with pragmatics. Finally, an increase in the presence of ADHD characteristics of impulsivity in these preschoolers is associated with an increase in language difficulties, while there is no such relation with inattention. It seems useful to evaluate the communication abilities of children regularly in the course of development and take ADHD characteristics into account. Finally recommendations on clinical use of the Children's Communication Checklist-2 (CCC-2, Bishop 2003) are discussed.

Contains fulltext : 69778.pdf (Publisher’s version ) (Closed access) Pain is a prominent issue in inguinal hernia repair research as its persisting appearance is a severe complication. The interest is also urged by the combination of a high number of repairs with an estimated risk for chronic postoperative pain of 11%. Almost every healthcare provider could encounter this complication. Pain is a complex study subject, mostly defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Various explanatory factors for pain following hernia repair have been reported. Most investigators, however, discuss only a few aspects. In the present review, these factors are collected to provide a more holistic synopsis of pain following hernia repair. It may be a resource for understanding this and other postsurgical pain.

Contains fulltext : 69802.pdf (Publisher’s version ) (Closed access) This study investigated changes of short-wavelength fundus autofluorescence (SW-AF) by retinal bleaching effects. All measurements were performed with the Heidelberg Retina Angiograph 2 (HRA 2). Initially, experimental imaging was done on a healthy eye after dark adaptation. Photopigment was bleached within the central 30 degrees of the fundus by HRA 2 excitation light. Then SW-AF imaging of this region was performed, and SW-AF of the surrounding, unbleached 25 degrees fundus region was subsequently studied by a wide-field lens. Next, another 30 degrees SW-AF image of the posterior pole was obtained after complete dark adaptation. Then an extra SW-AF examination was performed with 15 degrees temporal eccentricity, overlapping the original examination area. Finally, a successive image series was carried out on the dark-adapted eye to test for bleaching kinetics. The second and third experiments were also performed on eyes with macular dystrophies. Distinct regions of increased SW-AF were observed after strong illumination with the blue excitation light in all eyes studied. During light adaptation mean gray levels showed a saturation plateau after an initial steep increase. The resulting gray-value maps showed significant differences of pixel intensities between bleached and unbleached parts of the fundus. Two-dimensional density difference maps allowed analysis of visual pigment distribution and density in both healthy eyes and eyes with macular dystrophies. Our observations highlight the viability of objective, non-invasive evaluation of visual pigment in the healthy and diseased human retina by means of confocal fundus autofluorescence.

Contains fulltext : 69994.pdf (Publisher’s version ) (Closed access) OBJECTIVES/HYPOTHESIS: To define audiological application criteria for different implantable hearing aid devices. STUDY DESIGN: Retrospective study. METHODS: Comparisons were made between aided speech recognition scores obtained at conversational level (65 dB) in patients with the Vibrant Soundbridge (VSB) (n = 22), the Otologics middle ear transducer (MET) (n = 10), conventional hearing aids (behind-the-ears) (n = 47), and cochlear implants (CIs) (n = 123). RESULTS: In relation to hearing loss, only for mild hearing loss, speech recognition scores with VSB were comparable to that with conventional hearing aids. In the Otologics MET users, speech recognition scores were comparable with those of the conventional hearing aid users until a mean hearing loss of about 75 dB HL. At a sensorineural hearing loss of about 65 dB HL or more, the Otologics MET users have better speech recognition scores than the VSB users. For comparison with CI users, we followed a more conservative approach. In 90% of the users of a CI, speech recognition scores were better than those in: 1) patients with a conventional hearing aid and a mean hearing loss of about 95 dB HL or worse; 2) patients with an Otologics MET and a mean hearing loss of 85 dB HL or worse. CONCLUSIONS: Patients fitted with a VSB or an Otologics MET middle ear implant do not demonstrate better speech recognition scores than patients fitted with today's conventional hearing aids. Results might even been worse. However, the VSB and Otologics MET are a good option in patients with moderate (VSB) to severe (Otologics MET) sensorineural hearing loss and external otitis.

Item does not contain fulltext We present an overview of the history, development, technological advancements, current application, and future trends of cranial endoscopy. Neuroendoscopy provides a safe and effective management modality for the treatment of a variety of intracranial disorders, either tumoral or non-tumoral, congenital, developmental, and degenerative, and its knowledge, indications, and limits are fundamental for the armamentarium of the modern neurosurgeon.

Contains fulltext : 70450.pdf (Publisher’s version ) (Closed access) Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by the association of branchial and external ear malformations, hearing loss, and renal anomalies. The phenotype varies from ear pits to profound hearing loss, branchial fistulae, and kidney agenesis. The most common gene mutated in BOR families is EYA1, a transcriptional activator. Over 80 different disease-causing mutations have been published (www.healthcare.uiowa.edu/labs/pendredandbor/, last accessed 20 November 2007). We analyzed the EYA1 coding region (16 exons) from 435 families (345 at the University of Iowa [UI] and 95 at Boys Town National Research Hospital [BTNRH], including five at both) and found 70 different EYA1 mutations in 89 families. Most of the mutations (56/70) were private. EYA1 mutations were found in 31% of families (76/248) fitting established clinical criteria for BOR and 7% of families with questionable BOR phenotype (13/187). Severity of the phenotype did not correlate with type of mutation nor with the domain involved. These results add considerably to the spectrum of EYA1 mutations associated with BOR and indicate that the BOR phenotype is an indication for molecular studies to diagnose EYA1-associated BOR.

Contains fulltext : 71081.pdf (Publisher’s version ) (Closed access) The treatment of lumbar spinal stenosis is either conservative or surgical decompression. Recently, an interspinous decompression device (X-Stop) has been developed as an alternative. Patients treated with an X-Stop between 2003 and 2006 are subject of this study. The SF-36 Health Survey and Zurich Questionnaires are used. The data of pre- and post-operative self-rated questionnaires are collected and analysed by independent investigators. The data were statistically analysed. A good outcome was defined when the mean score at the ZQ for satisfaction was at maximal 2.0, and the mean improvement of the severity score was at least 0.5, and also for vitality score. For relations between outcome and gender, smoking, BMI, orthopaedic co-morbidity, number of implanted X-Stops were sought. The change in SF-36 scales was related to the outcome. Sixty-five patients did undergo implantation of an X-Stop. The mean age was 64.4 +/- 10.0 years (range: 37.0-85.0 years). 31.1% Of the patients had a good outcome. A good outcome was not related to smoking, BMI, number of implanted X-Stops. However, a good outcome was related to the absence of orthopaedic co-morbidity or male gender. Patients with a good outcome had significantly a better improvement of the scales of the SF-36 concerning physical pain or impairment. The X-Stop does improve the clinical situation. However, a good outcome is achieved less often than previously reported. Probable explanations are discussed.

Contains fulltext : 36578.pdf (Publisher’s version ) (Closed access) Otosclerosis is a progressive hearing loss characterized by an abnormal bone homeostasis of the otic capsule that leads to stapes fixation. Although its etiology remains unknown, otosclerosis can be considered a complex disease. Transforming growth factor-beta 1 (TGF-beta1) was chosen for a case-control association study, because of several non-genetic indications of involvement in otosclerosis. Single nucleotide polymorphism (SNP) analysis in a large Belgian-Dutch sample set gave significant results (P = 0.0044) for an amino acid changing SNP, T263I. Analysis of an independent French population replicated this association with SNP T263I (P = 0.00019). The results remained significant after multiple testing correction in both populations. Haplotype analysis and the results of an independent effect test using the weighted haplotype (WHAP) computer program in both populations were both compatible with SNP T263I being the only causal variant. The variant I263 is under-represented in otosclerosis patients and hence protective against the disease. Combining the data of both case-control groups for SNP T263I with a Mantel-Haenszel estimate of common odds ratios gave a very significant result (P = 9.2 x 10(-6)). Functional analysis of SNP T263I with a luciferase reporter assay showed that the protective variant I263 of TGF-beta1 is more active than the WT variant T263 (P = 1.6 x 10(-6)). On the basis of very low P-values, replication in an independent population and a functional effect of the protective variant, we conclude that TGF-beta1 influences the susceptibility for otosclerosis, and that the I263 variant is protective against the disease.

Contains fulltext : 53618.pdf (Publisher’s version ) (Closed access) Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

Contains fulltext : 51677.pdf (Publisher’s version ) (Closed access) Pharmacokinetic models can be differentiated into two groups: physiological-based models and empirical models. Traditionally the pharmacokinetics of volatile anaesthetics are described using physiological-based models together with the respective tissue-blood distribution coefficients. The compartments of the empirical model have no anatomical equivalents and are merely the product of the mathematical procedure for parameter estimation. The end expiratory concentration of volatile anaesthetics is approximately equal to the arterial concentration and, therefore, the description of the transition between plasma and effect site for volatile anaesthetics plays a central role. The most important parameter here is the k(e0) value which is a time constant and describes the time delay for the transition from the central compartment to the calculated effect compartment. The k(e0) values for sevoflurane and isoflurane are the same but the concentration balance between the end-tidal concentration and the effect compartment occurs twice as quickly with desflurane. In clinical practice volatile anaesthetics are normally combined with N(2)O and/or opioids. This results in an additive interaction between volatile anaesthetics and N(2)O but a synergistic interaction of volatile anaesthetics with opioids. However, there are relatively few investigations on the interactions between the clinically widely used combination of volatile anaesthetics, N(2)O and opioids.

Contains fulltext : 35228.pdf (Publisher’s version ) (Closed access) Otosclerosis is a common form of hearing impairment among white adults with a prevalence of 0.3-0.4%. It is caused by abnormal bone homeostasis of the otic capsule that compromises free motion of the stapes in the oval window. Otosclerosis is in most patients a multifactorial disease, caused by both genetic and environmental factors. In some cases, the disease is inherited as a monogenic autosomal dominant trait, sometimes with reduced penetrance. However, families large enough for genetic linkage studies are extremely rare. To date, five loci (OTSC1-5) have been reported, but none of the responsible genes have been cloned yet. An additional locus, OTSC6, has been reported to the HUGO nomenclature committee but the relevant linkage study has not been published. In this study, a genome-wide linkage study was performed in a large Greek pedigree segregating autosomal dominant otosclerosis. A seventh locus, OTSC7, was localized on chromosome 6q13-16.1 with a multipoint LOD score of 7.5 in the 13.47 cM region defined by markers D6S1036 (centromeric) and D6S300 (telomeric). Linkage analysis of this new locus in 13 smaller Belgian and Dutch families has identified one family from The Netherlands in which allele segregation suggests linkage to this region. The overlap between the critical regions of these two families is a 1.06 Mb interval between the genetic markers D6S1036 (centromeric) and D6S406 (telomeric) on chromosome 6q13.

Contains fulltext : 53292.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine whether intra-individual changes in eustachian tube (ET) function induced by local application of a histamine phosphate solution can be detected using an improved sonotubometer. DESIGN: The function of the ET was measured with a revised sonotubometer before and after histamine was applied to the nasopharyngeal ostium of the ET. SETTING: Tertiary referral hospital. PATIENTS: Twenty-five otologically healthy adults. INTERVENTIONS: A histamine phosphate solution with a concentration of 16 mg/mL was applied to the nasopharyngeal ostium of the ET using a pressure nebulizer. MAIN OUTCOME MEASURES: The number of openings during 10 acts of swallowing. This outcome value could range from 0 to 10. The number of ET openings before and after histamine application was compared. RESULTS: The mean number of ET openings dropped dramatically: from 8.4 before application of histamine to 2.7 after application. This difference was statistically significant; there was a mean difference of 5.6 (95% confidence interval, 4.4-6.9; P < .001). CONCLUSION: Sonotubometry is capable of detecting intra-individual changes in ET function and may therefore be a very useful tool in monitoring and/or clinical research of ET dysfunction or function.

Contains fulltext : 52398.pdf (Publisher’s version ) (Closed access) BACKGROUND: The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. METHODS: The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. RESULTS: The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). CONCLUSIONS: A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required.

Contains fulltext : 52397.pdf (Publisher’s version ) (Closed access) BACKGROUND: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. METHODS: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. RESULTS: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of >98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C>T (p.R134X) in PCDH15 and c.1606T>C (p.C536S) in USH2A. CONCLUSION: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool.

Contains fulltext : 52793.pdf (Publisher’s version ) (Closed access) A cross-sectional questionnaire survey was performed. The objectives of the study were to assess the psychosocial impact of current voice complaints as perceived by student-teachers with voice complaints in comparison with student-teachers without voice complaints, and to observe the pattern of risk factors in relation to their voice handicap. Subjects in the general population without a voice-demanding profession were selected as a reference group for limited comparison with the total group of student-teachers (future professional voice users). The respondents to the questionnaires were anonymous. Among the student-teachers, 17.2% reported current voice complaints in comparison with 9.7% of the reference group, and the odds ratio was 1.94, which showed the relative risk. Student-teachers had significantly greater total Voice Handicap Index (VHI) scores than the reference group (P = 0.034). The VHI subscale scores were not significantly different (P > 0.05). Student-teachers who reported current voice complaints had a significantly higher total VHI and subscale scores than student teachers without voice complaints (P < 0.001). Of the student-teachers without voice complaints, 17.0% had VHI scores greater than the 75th percentile. These persons may be neglecting their voice handicap and probably represent the false-negative cases in the estimation of voice complaints. Logistic regression analysis of each of the given risk factors with the VHI as the independent variable showed that the perceived negative influence of the given risk factors on their voices was significantly greater with increasing VHI scores across the VHI range. A significant correlation was observed between the number of perceived risk factors and increasing VHI scores across the VHI range. An increased awareness of risk factors in relation to their voice handicap would serve to motivate student-teachers to change factors that contributed to their voice problem. Attention to all risk factors, which the subjects perceive to be a risk, would aid in effective management of their voice handicap.

Contains fulltext : 52594.pdf (Publisher’s version ) (Closed access) BACKGROUND: Our study aims to identify anatomical characteristics of glaucoma filtering blebs by means of slit lamp-adapted optical coherence tomography (SL-OCT) and to identify new parameters for the functional prognosis of the filter in the early post-operative period. METHODS: Patients with primary open-angle glaucoma, aged 18 years and older, scheduled for primary trabeculectomy at the Department of Ophthalmology, Radboud University Nijmegen Medical Centre, were considered for our study. All patients underwent standardized trabeculectomy with intra-operative application of mitomycin C. The filtering blebs were evaluated clinically and with SL-OCT on day 1 and 1, 2, 4 and 12 weeks following surgery. The resulting data were analysed and weighed against surgical success. To better understand the SL-OCT data a small comparative histologic study was performed. RESULTS: The study included 20 eyes of 20 patients. After completion of our study, 15 eyes of 15 patients (mean age+/-SD 67 +/- 16 years) were eligible for data analysis and 5 eyes missed at least one follow-up visit. Filtering surgery was considered successful (intraocular pressure < or = 21 mmHg without antiglaucomatous medication) in 11 of 15 eyes. SL-OCT frequently demonstrated multiple hypo-reflective layers within Tenon's capsule ("striping" phenomenon) in the first post-operative week. Presumably, these layers corresponded with drainage channels in the histological specimen. These channels were present in functional filters but not in the failures. In addition, the visualisation of the sclera below the filtering zone was better defined in failures compared with successful filtering blebs ("shading" phenomenon). We observed no differences in the volume and clinical aspect of the blebs in the successful group compared with the unsuccessful group. CONCLUSIONS: Successful filtering blebs show characteristic optical properties on SL-OCT. These phenomena suggest a diffusely enhanced fluid content and the presence of intra-bleb drainage channels in functional filtering blebs.

Item does not contain fulltext AIMS: To determine and compare the accuracy and reproducibility of GDx variable cornea compensation (VCC) scanning laser polarimetry (SLP) with VCC, Heidelberg retina tomograph (HRT) I confocal scanning laser ophthalmoscopy (CSLO), and clinical assessment of stereoscopic optic nerve head (ONH) photographs for diagnosing glaucoma. METHODS: One eye each of 40 healthy subjects, 48 glaucoma patients, and six patients with ocular hypertension were measured with SLP-VCC and CSLO. Simultaneous stereoscopic ONH photographs were also obtained. Sixteen photographs of healthy and glaucomatous eyes were duplicated for assessing intraobserver agreement. Four glaucoma specialists, four general ophthalmologists, four residents in ophthalmology, and four optometrists classified the ONH photographs as normal or glaucomatous. For SLP-VCC, the nerve fiber indicator (NFI) was evaluated. For CSLO, the Moorfields regression analysis (MRA) and the Bathija linear discriminant function (LDF) were used. Sensitivity, specificity, percentage of correctly classified eyes, and intra- and interobserver agreement, expressed as kappa (kappa) were calculated. RESULTS: SLP-VCC had the highest diagnostic accuracy, with a sensitivity, specificity, and overall correct classification of 91.7%, 95.0% and 93.2%, respectively. CSLO, expressed as Bathija LDF and MRA, had a diagnostic accuracy comparable to glaucoma specialists and general ophthalmologists with an overall accuracy of 89.8%, 86.4%, 86.7% and 85.2%, respectively. Residents classified the fewest eyes correctly. Intraobserver agreement for classifying the ONH photographs ranged between 0.48 (within residents) and 0.78 (within glaucoma specialists). The interobserver agreement ranged between 0.45 (between residents) and 0.74 (between glaucoma specialists). The agreement between observers and CSLO MRA (kappa, 0.68) was statistically significantly higher (p

Contains fulltext : 49790.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To describe the different imaging modalities used for the diagnosis and classification of hydrocephalus, their role in defining the optimal treatment of hydrocephalus and to define the optimal preoperative diagnostics for endoscopic third ventriculocisternostomy (ETV). METHODS: An overview on available imaging modalities for hydrocephalus will be given and their pros and cons discussed. In addition, different aspects of the treatment of hydrocephalus by shunts and by ETV will be highlighted. DISCUSSION: The role of the technical aspects of performing an ETV, the role of the surgeon's philosophy, the role of the urgency of the procedure, and the role of informed consent on the requirements for the imaging of the hydrocephalus will be discussed. CONCLUSION: The authors conclude that MRI is a conditio sine qua non for ETV in elective surgical cases.

Contains fulltext : 50281thijssen.pdf (Publisher’s version ) (Closed access) Despite the social impact of repetitive strain injury (RSI), little is known about its pathophysiological mechanism. The main objective of this study was to assess the local muscle oxygenation (mVO2) and blood flow (mBF) of the forearm in individuals with RSI during isometric contractions of the forearm. We employed the non-invasive optical technique near-infrared spectroscopy to assess forearm VO2 and BF. These variables were assessed at 10%, 20%, and 40% of their individual maximal voluntary strength. Twenty-two patients with RSI symptoms in both arms (bilateral RSI) and 30 healthy age-matched subjects participated in this cross-sectional study. The results showed lower mVO2 during exercise and a reduced mBF after exercise. The results suggest that mVO2 and mVO2 are lower in the forearms of individuals with RSI compared with their controls at similar working intensities. This finding indicates that the underlying vasculature may be impaired. Although these findings contribute to the understanding of RSI, future research is necessary to further unravel the mechanisms of this area.

Contains fulltext : 49620.pdf (Publisher’s version ) (Closed access) A novel TECTA mutation, p.R1890C, was found in a Dutch family with nonsyndromic autosomal dominant sensorineural hearing impairment. In early life, presumably congenital, hearing impairment occurred in the midfrequency range, amounting to about 40 dB at 1 kHz. Speech recognition was good with all phoneme recognition scores exceeding 90%. An intact horizontal vestibuloocular reflex was found in four tested patients. The missense mutation is located in the zona pellucida (ZP) domain of alpha-tectorin. Mutations affecting the ZP domain of alpha-tectorin are significantly associated with midfrequency hearing impairment. Substitutions affecting other amino acid residues than cysteines show a significant association with hearing impairment without progression. Indeed, in the present family progression seemed to be absent. In addition, the presently identified mutation affecting the ZP domain resulted in a substantially lesser degree of hearing impairment than was previously reported for DFNA8/12 traits with mutations affecting the ZP domain of alpha-tectorin.

Contains fulltext : 50720.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To report hearing impairment and vestibular and ocular features in a Dutch DFNA11 family and to compare these results to reported data on three other DFNA11 families. STUDY DESIGN: Family study. METHODS: Regression analysis was performed in relation to age to outline the development of hearing thresholds and speech recognition scores. Vestibular and ocular functions were examined. RESULTS: First symptoms of hearing impairment started between the ages of 4 and 43 years. Most of the audiograms were symmetric and flat or downsloping. The annual threshold deterioration increased from 0.2 to 2.6 dB per year at 0.25 to 8 kHz in the longitudinal analyses and in the cross-sectional analysis from 0.3 to 0.9 dB per year. The speech recognition score was quite good, deteriorating by 0.9% per year from a 90% score at the age of 36 years onward. Remarkably, extensive ocular examination including corrected visual acuity and refraction measurements, slit-lamp examination, ophthalmoscopy, Goldmann perimetry, electroretinography and electro-oculography revealed signs of subclinical retinal dysfunction. None of the patients showed the classic triad of retinitis pigmentosa. Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the mutation carriers were fairly similar to previously described DFNA11 families. CONCLUSION: Even though the diverse mutations are located in different regions of the myosin VIIa gene, the cochleovestibular phenotype is fairly similar in all DFNA11 families. Surprisingly, only in this family was subclinical retinal dysfunction detected.

Contains fulltext : 50690.pdf (Publisher’s version ) (Closed access) PURPOSE: Yoked prism spectacles (eccentric viewing spectacles [EVS]) facilitate eccentric viewing in patients with bilateral central scotomas. This study was conducted to evaluate the long-term success and patient satisfaction of this type of low-vision aid. METHODS. In this retrospective cross-sectional study, we reviewed the low-vision rehabilitation records of all patients who received EVS since 1993. With an 18-item survey, 191 patients were questioned about the wearing characteristics, advantages, and disadvantages of the EVS. Descriptive and nonparametric statistics were applied to compare regular users with those persons who no longer use the EVS. RESULTS: The response rate was 83.2% and the average follow-up time was 4.5 years. Forty percent of all patients still used the EVS. The main disadvantages of these spectacles, mentioned mainly by the nonusers, included the heavy weight (41%), perception of curved lines (46%), dizziness during walking (46%), and poor cosmetic appearance (25%). Many successful long-term users considered the EVS suitable for home activities (86%) and walking in the street (70%) and reported that this device reduced eccentric viewing (77%), created better vision in the center of their visual field (67%), and helped with recognition of objects and faces (64%). CONCLUSIONS: The prescription of EVS aids eccentric viewing in patients with dense central scotomas. Although associated with a number of disadvantages and side effects, 40% of the patients continued to use EVS. The results of this study indicate that patients who experience difficulties with eccentric fixation are most likely to benefit from these low-vision aids. A thorough explanation of the advantages and disadvantages of the EVS is important to prevent unnecessary disappointments.

Item does not contain fulltext BACKGROUND: In circumscribed choroidal hemangiomas (CCH) a long observation period and decreased visual acuity before treatment are risk factors for poor visual outcome. Therefore, we studied the use of limited, single spot photodynamic therapy (PDT) with Visudyne for the timely treatment of CCH. METHODS: Six consecutive patients with CCH, and metamorphopsia but (near) normal visual acuity were treated with PDT, using a single spot covering only the most prominent part of the tumour, and a radiance exposure of 50 J/cm(2). Start of treatment was 6 min following a 1-min infusion with Visudyne (6 mg/m(2) BSA), using a diode laser (692 nm). RESULTS: In all patients, the metamorphopsia disappeared, the OCT images returned to a normal foveal contour, and visual acuity remained 20/20 or improved to 20/20. In five patients, the tumour became ultrasonographically undetectable; in three after one PDT session, in one patient after two and in another patient after three PDT sessions. The last patient had a residual tumour height of 1.2 mm, but no metamorphopsia, a normal foveal contour on OCT, and fluorescein angiography showed no residual leakage. CONCLUSION: The present series demonstrates that single spot PDT might be an effective treatment for CCH with a visual acuity > or =20/30, without serious side-effects during a follow-up of at least 18 months.

Contains fulltext : 50908.pdf (Publisher’s version ) (Closed access) Assessment of initial disease severity after subarachnoid haemorrhage (SAH) remains difficult. The objective of the study is to identify biochemical markers of brain damage in peripheral blood after SAH. Hospital admission S100beta, glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) serum levels were analysed in 67 patients with SAH. Disease severity was determined by using the World Federation of Neurological Surgeons (WFNS) scale and the Fisher CT (computerized tomography) grading scale. Mean astroglial serum concentrations taken at hospital admission were increased (S100beta 2.8-fold and GFAP 1.8-fold) compared with the upper limit of normal laboratory reference values (P95). The mean NSE concentration was within normal limits. S100beta (P < 0.001) and GFAP (P =0.011) but not NSE levels were higher in patients who were in coma at the time of hospital admission compared with patients who were not. Similarly S100beta and GFAP but not NSE serum levels increased with higher WFNS scores, raised intracranial pressure and higher CT Fisher grade scores. Concerning the location of the aneurysm, S100beta and GFAP serum levels were within normal limits after a perimesencephalic type of haemorrhage and significantly increased after aneurysmal type SAH. Increased glial (S100beta and GFAP) but not neuronal (NSE) protein serum concentrations are found after SAH, associated to the clinical severity of the initial injury.

Purpose Several types of inborn errors of the O-glycan biosynthesis are known, leading to clinically very distinct phenotypes. Children with O-mannosyl glycan biosynthesis defects commonly present as a severe form of congenital muscular dystrophy with decreased alpha-dystroglycan staining, congenital eye anomalies, and brain migration defects. Alpha-dystroglycan is an O-mannosylated glycoprotein with additional mucin type O-glycans. Methods Based on overlapping clinical features with O-mannosyl glycan defects, especially with muscle-eye-brain disease, the authors performed a muscle biopsy in a child with severe congenital hypotonia, high myopia, partial pachygyria, mental retardation, cutis laxa, and an inborn error affecting the biosynthesis of both mucin type O-glycans and N-linked glycans. Results The histology showed no signs of muscle dystrophy, but a mild myopathy with slight increase in the muscle fiber diameter variability and type I fiber predominance. No significant decrease in the alpha-dystroglycan staining was detected; therefore, in spite of the phenotypic similarities the authors could not confirm the role of abnormal dystroglycan in the etiology of the muscle weakness and the developmental anomalies. Conclusions High myopia, muscle weakness, and cortical neuronal migration abnormalities are common in disorders of O-mannosylation and also observed in the authors’ patient. However, compared to the severe generalized defect observed in mannosyl glycan defects, in this child the cerebral white matter and cerebellum were spared, and no muscle dystrophy could be confirmed. This is the first description of high myopia in cutis laxa syndrome in combination with congenital disorders of glycosylation.

Contains fulltext : 50873.pdf (Publisher’s version ) (Closed access) BACKGROUND: The present preliminary study documents the effects of a selective nerve root block (SNB) with short or long acting local anaesthetic compared with baseline measurements in patients with chronic low back pain radiating to the leg with maximum pain in one dermatome (L4). METHODS: Ten consecutive patients underwent 20 controlled SNBs at L4 with ropivacaine 0.25% and lidocaine 1% in a prospective, randomized, double blind, crossover fashion. Baseline measurements included sensory function (assessed by pinprick on both unaffected and painful leg) and pain (Verbal Numeric Rating Scale; VNRS, 0-10). A change in size of areas with altered sensory function >10% and a VNRS change of 2 points were considered clinically significant. P-values

Contains fulltext : 49730.pdf (Publisher’s version ) (Closed access) Pain is the major presenting symptom of chronic pancreatitis. Patients with chronic pancreatitis experience substantial impairments in health-related quality of life. Pain may be considered as the most important factor affecting the quality of life. The pathogenesis of pancreatic pain is poorly understood. The cause of pain in chronic pancreatitis is probably multifactorial. This article discusses the various hypotheses that have been suggested to underlie pain. Special attention is paid to the concept of autonomous central sensitisation and hyperalgesia as a cause of pain. Strict abstinence from alcohol is the first step of chronic pancreatic pain management. As a second step, it is important to exclude treatable complications of chronic pancreatitis, such as pseudocysts. Symptomatic treatment with analgesics is often unavoidable in patients with chronic pancreatitis. Acetaminophen, non-steroidal anti-inflammatory drugs and eventually opioids are suitable. Several trials have been performed with pancreatic enzymes, but a meta-analysis demonstrated no significant benefit in terms of pain relief. The treatment of chronic pancreatic pain requires a multidisciplinary approach that tailors the various therapeutic options to meet the need of the individual patient.

Contains fulltext : 51141.pdf (Publisher’s version ) (Open Access) BACKGROUND: Frequent active opening of the eustachian tube (ET) allows ventilation of the middle ear and equilibration of pressure changes. Active opening is accomplished by the contraction of the paratubal muscles during swallowing. Because a disturbance of the ventilatory function of the ET may contribute to the development of otitis media with effusion, it is important to investigate ET function. Sonotubometry can be used to detect whether the ET can open or not during swallowing acts. METHODS: We developed a sonotubometer to test ET ventilatory function in 36 healthy adults. The width of the test signal frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the loudness was 95 dB. To test reproducibility, testing took place in two sessions of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in 91.6 per cent of the subjects in at least one of the two measurements. The first and the second measurements were highly correlated, with a Spearman's coefficient of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET function in otologically healthy adults, although, in a few cases, ET opening was not registered. Furthermore, we confirmed that our sonometric test equipment had acceptable reproducibility. Sonotubometry is a promising method for assessing ventilatory ET function. Research is ongoing to test the discriminative power of sonotubometry in children with various otological conditions.

Contains fulltext : 50194.pdf (Publisher’s version ) (Closed access) Median entrapment neuropathy or carpal tunnel syndrome is uncommon in children. The majority of cases are related to genetic conditions which result in skeletal dysplasia or altered connective tissue characteristics, direct injury to the median nerve caused by intensive sports or trauma, or hereditary neuropathy with liability to pressure palsies. This report describes a 10-year-old patient with Alagille syndrome who presented with poor fine motor skills because of an entrapment neuropathy of the median nerve at the wrist. This condition was probably caused by intermittent external compression at the wrists due to years of rubbing both wrists and hands to relieve pruritus. To our knowledge, median neuropathy has never been associated with Alagille syndrome, although severe pruritus is considered a major symptom and many patients exhibit widespread scratching and rubbing.

Contains fulltext : 51125.pdf (Publisher’s version ) (Closed access) The performance of continuous bilateral sciatic nerve blocks under ultrasonographic control using stimulating catheters is described in a 4-year-old child with VACTERL syndrome. Ultrasound showed an abnormal vascular and nerve supply to the lower limbs. The use of ultrasound guidance made successful continuous sciatic nerve blocks possible in a child in whom the traditional method of nerve localisation was unlikely to succeed for anatomical reasons.

Contains fulltext : 51311.pdf (Publisher’s version ) (Open Access) Stem cells have been recognized and intensively studied for their potential use in restorative approaches for degenerative diseases and traumatic injuries. In the central nervous system (CNS), stem cell-based strategies have been proposed to replace lost neurons in degenerative diseases such as Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (Lou Gehrig's disease), or to replace lost oligodendrocytes in demyelinating diseases such as multiple sclerosis. Stem cells have also been implicated in repair of the adult spinal cord. An impact to the spinal cord results in immediate damage to tissue including blood vessels, causing loss of neurons, astrocytes, and oligodendrocytes. In time, more tissue nearby or away from the injury site is lost due to secondary injury. In case of relatively minor damage to the cord some return of function can be observed, but in most cases the neurological loss is permanent. This review will focus on in vitro and in vivo studies on the use of bone marrow stromal cells (BMSCs), a heterogeneous cell population that includes mesenchymal stem cells, for repair of the spinal cord in experimental injury models and their potential for human application. To optimally benefit from BMSCs for repair of the spinal cord it is imperative to develop in vitro techniques that will generate the desired cell type and/or a large enough number for in vivo transplantation approaches. We will also assess the potential and possible pitfalls for use of BMSCs in humans and ongoing clinical trials.

Objectives: We compared classroom performance of children with a cochlear implant (CI) with that of their normal-hearing peers in mainstream education. Methods: Thirty-two CI children in mainstream education, congenitally or prelingually deaf, participated in this study, as did 37 hearing classmates. Their teachers filled out 2 questionnaires: the Assessment of Mainstream Performance (AMP) and the Screening Instrument for Targeting Educational Risk (SIFTER). A high Fletcher index and open-set speech perception scores were obtained. Results: The children with CIs scored above average on the AMP and sufficiently well in all but one area (communication) of the SIFTER questionnaire. Class rankings did not differ significantly between the CI students and their normal-hearing peers. Overall, the normal-hearing group outperformed the CI group. The classroom performance of CI children correlated negatively with duration of deafness and age at implantation. All longitudinal audiological data of the CI children showed improvement in open-set speech recognition. Conclusions: Although the results are encouraging, the CI group scored significantly less well than their normal-hearing peers on most questionnaire domains of both the AMP and the SIFTER. The most important variables for the outcome in this study were age at implantation and duration of deafness.

Contains fulltext : 51217.pdf (Publisher’s version ) (Open Access) The aim of this study was to test the efficacy of shortterm transcutaneous electrical nerve stimulation (TENS) treatment in chronic pain with respect to pain intensity and patients' satisfaction with treatment results. We therefore performed a randomised controlled trial comparing TENS and sham TENS. Patients, researchers and therapists were blinded for treatment allocation. One hundred and sixty-three patients with chronic pain referred to the Pain Centre entered the study. Conventional TENS and sham TENS were applied in the segments of pain, for a period of ten days. Outcome measures were pain intensity (visual analogue scale) and patients' satisfaction with treatment result (yes or no). The proportions of patients satisfied with treatment result differed significantly for TENS compared to sham TENS (58 and 42.7% respectively, chi(2)=3.8, p=0.05). However, no differences in pain intensity were found for patients treated with TENS or sham TENS. Only for patients satisfied with treatment results pain intensity gradually decrease equally both for TENS and sham TENS with repeated treatment application.

Contains fulltext : 51288.pdf (Publisher’s version ) (Closed access) It has long been recognized that from the first months of life auditory perception plays a crucial role in speech and language development. Only in recent years, however, is the precise mechanism of auditory development and its interaction with the acquisition of speech and language beginning to be systematically revealed. This paper presents the results of a series of studies exploring the relevance of electrophysiological measurements for the objective diagnosis of children with language and speech disorders. In the first, retrospective, study, an inventory was made of clinical neurological, neuropsychological, logopedic and neurophysiological findings obtained from 43 children referred to the Paediatric Neurology Centre for the diagnosis of their speech and language deficits. Neurophysiological abnormalities were found in 95% of these children, among these deviant auditory evoked potentials (AEVPs). The second study demonstrated developmental trends in the waveform of the cortical AEVPs up to age 6 years; the implications for longitudinal studies are discussed. Preliminary results from the third study show emerging differences in auditory event-related potentials (AERPs) for young children who are at risk for developmental dyslexia based on their family history. These findings underscore the clinical usefulness of neurophysiological measures for the diagnosis of speech-language disorders. Clinical protocols are further developed and tested.

Contains fulltext : 51266.pdf (Publisher’s version ) (Closed access) Artemisinin derivatives are becoming the first-line treatment for uncomplicated malaria in areas with widespread resistance to chloroquine. Although generally safe and well tolerated, it has been suggested from animal experiments, and more recently from one human study with artemether-lumefantrine, that these compounds are potentially neurotoxic, affecting particularly the brainstem auditory pathways. We report here the auditory analyses of 15 volunteers who underwent an experimental human malaria infection and were treated with artemether-lumefantrine. The subjects underwent audiological examination before the start of the study, during infection, and after treatment. Examination included standard tone audiometry, high frequency tone audiometry and auditory brainstem response (ABR). No effects on hearing loss that were deemed to be caused by drug treatment were found using tone audiometry. ABR analysis similarly failed to demonstrate any auditory pathway damage in the volunteers after treatment. We have thus not found any clear evidence of a detrimental effect on the auditory system by artemether-lumefantrine treatment in uncomplicated malaria. Our results support the continued implementation of artemisinin derivatives in the fight against drug-resistant malaria.

Contains fulltext : 50148.pdf (Publisher’s version ) (Closed access) OBJECTIVES: The objectives of this descriptive, retrospective study were to evaluate quality of life, hearing, and vision in patients with Usher syndrome type I with and without cochlear implant. METHODS: Quality of life (QoL) of 14 patients with Usher type I (USH1) with a cochlear implant (CI) (seven adults, seven children) was compared with those of 14 patients with USH1 without a CI (12 adults, two children) by means of three questionnaires: NCIQ, SF12, and the Usher Lifestyle Survey. Additional information on hearing level was obtained by the equivalent hearing loss (EHL) principle and on the visual deterioration by the functional vision score (FVS). RESULTS: A significant benefit of CI was seen in the hearing-specific questionnaire NCIQ. This difference could not be detected in the generic SF12 survey. The Usher Lifestyle Survey indicated that patients with USH1 with a CI tend to be able to live an independent life more easily than the profoundly deaf unimplanted patients with USH1. EHL and FVS scores varied in both groups. CONCLUSIONS: Overall QoL can be enhanced by CI in patients with USH1, although effects are mostly seen in hearing-related QoL items.

Contains fulltext : 51132.pdf (Publisher’s version ) (Closed access) There is a need to evaluate the effectiveness of stuttering treatment programs delivered in domestic and international contexts and to determine if treatment delivered internationally is culturally sensitive. Evaluation of the effectiveness of the ISTAR Comprehensive Stuttering Program (CSP) within and across client groups from the Netherlands and Canada revealed generally positive results. At 2 years post-treatment both groups were maintaining statistically significant reductions in stuttering frequency and improvements in attitudes, confidence, and perceptions as measured by the Revised Communication Attitude Inventory (S24), Perceptions of Stuttering Inventory (PSI), and the approach scale of the Self-Efficacy Scaling by Adult Stutterers (SESAS). Data pooled across the groups on these measures gave evidence of a global treatment effect with standardized effect sizes ranging from typical to larger than typical in the behavioural sciences. Only two differences between the groups emerged: differences in speech rate and perception of self. Given that these groups represent two distinct cultures, differences were discussed in terms of whether they could be due to cultural, methodological, or other variables. Overall, results suggest that, the CSP appears to be similarly effective in both cultures and thus, sufficiently sensitive to the culture of Dutch adults who stutter. Educational objectives: The reader will be able to (a) describe a methodology that can be used in a clinical setting to evaluate the long-term effectiveness of stuttering treatment with adults, (b) describe some of the challenges in developing a model of clinically meaningful outcome, (c) explain the rationale for the need for cross-cultural investigations of treatment outcome, and (d) summarize speech and self-report results of the cross-cultural evaluation of an integrated stuttering treatment program.

Item does not contain fulltext Research on mechanisms of drug action, and preclinical screening of molecules with a potential activity on neuropathic pain requires extensive animal work. The chronic constriction injury model is one of the best-characterized models of neuropathic pain behavior in rats, but requires extensive time consuming operations and animal handling. The formalin test is easier to perform, and a well validated model. The latter may serve as an effective prescreening test of molecules and may facilitate drug targeting. In the present study the activity of different pharmacological reference compounds was tested in rats and gerbils on the cold plate for animals that had undergone chronic constriction injury and in the second phase of the formalin test. In rats, a comparable outcome in both test conditions was observed for morphine, fentanyl, MK-801 and flunarizine. Clonidine had more activity in the second phase of the formalin test, whereas baclofen, tramadol, amitryptiline, ketamine and topiramate showed more activity in the cold plate. In gerbils, both test conditions yielded comparable results for fentanyl and ketoprofen. Tramadol and CP-96345 tended to have more activity in the second phase of the formalin test, whereas morphine, SR-48968, SR-142801 and R116301 demonstrated more activity in the cold plate test. This study demonstrates a good correlation between the second phase of the formalin test and the cold allodynia in the CCI model for, both for rats and gerbils. Drugs with a proven activity in humans, used as reference compounds, also showed good pharmacological activity in this animal study.

Item does not contain fulltext Treatment of patients with prolactinomas consists primarily of dopamine agonists (DA). Cerebrospinal fluid (CSF) leakage has sporadically been reported in patients with macroprolactinomas treated with short-acting DA such as bromocriptine. Little is known on the incidence of this complication in patients treated with the long-acting D2 specific DA cabergoline. We report three patients with CSF leakage shortly after initiation of cabergoline treatment for macroprolactinoma. All three patients responded rapidly to cabergoline (CAB) by shrinkage of the tumor and release of the optic chiasm compression. The CSF leakage occurred within 10 days after initiation of treatment. CAB treatment was not discontinued. In one patient the CSF leakage ceased spontaneously, with no additional therapy. The second patient had a surgical repair of the CSF fistula, permitting cabergoline to be continued without a recurrence of the CSF leakage. The third patient refused surgical repair of the sellar defect. In this patient the cabergoline dosage was temporarily decreased with no effect on the CSF leakage. Four years later, the CSF leakage is unchanged in this patient, whilst no other complications occurred during the follow-up. No infectious complications occurred in these three patients. In conclusion, patients with large, invasive macroprolactinomas are at risk of CSF leakage during medical treatment with CAB. It is advisable to warn these patients for occurrence of this complication and to monitor them closely especially during the first months of treatment.

Contains fulltext : 51290.pdf (Publisher’s version ) (Closed access) Streptococcus pneumoniae is a major bacterial pathogen involved in the development of otitis media. The pathogenic mechanisms of this middle ear disease, including the bacterial adherence mechanisms to the mucosal epithelial cells of the host, are poorly understood. In this study, the role of glycosaminoglycans in the adhesion of pneumococci to mucosal epithelial cells is examined. Both nasopharyngeal epithelium from rats and an oral epithelial cell line were used for pneumococcal adherence experiments. Preincubation of pneumococci with heparin, heparan sulfate (HS) and to a lesser extent, chondroitin 4-sulfate (C-4S), was found to inhibit attachment of S. pneumoniae to oral epithelial cells, while dermatan sulfate and hyaluronate did not interfere with pneumococcal binding. Enzymatic removal of HS moieties by heparinase III from nasopharyngeal epithelial cells abolished the attachment of pneumococci to nasopharyngeal epithelium. This study demonstrates that heparin, HS and C-4S are involved in pneumococcal binding to mucosal epithelial cells. This knowledge may contribute to the development of a new prophylactic strategy for otitis media.