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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.

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 : 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 : 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 : 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 : 69373_2.pdf (Publisher’s version ) (Closed access) Contains fulltext : 69373_1.pdf (author's version ) (Open Access) In a Dutch pedigree suffering from autosomal dominant nonsyndromic hearing impairment (ADNSHI), linkage was found to the locus for DFNA15, with a two-point logarithm of the odds (LOD) score of 5.1. Sequence analysis of the POU4F3 gene that is involved in DFNA15 revealed the presence of a missense mutation (c.865C>T), segregating with the deafness in this family. The mutation is predicted to result in the substitution of a phenylalanine residue for a leucine residue (p.L289F) in the POU homeodomain of the transcription factor POU4F3. Mutation analysis of the POU4F3 gene in 30 patients suffering from dominantly inherited hearing impairment revealed a second novel missense mutation (c.668T>C), resulting in the substitution of a proline for a leucine residue (p.L223P) within the POU-specific DNA-binding domain of the protein. In a computer model describing the structure of the two DNA-binding domains, the alterations are predicted to affect the tertiary structure of these domains. Transient transfection studies showed that whereas the wild-type POU4F3 is located almost exclusively in the nucleus, part of the mutant proteins was also present in the cytoplasm. In addition, both mutant proteins showed greatly reduced capability for binding to DNA as well as transcriptionally activating reporter gene expression. Together, our results describe the identification of the first missense mutations in POU4F3 causing DFNA15. Furthermore, mutations in this gene do not seem to be a rare cause of hearing impairment in the Dutch population, and the POU4F3 gene may thus be suitable for implementation in diagnostic testing.

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 : 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 : 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.

Item does not contain fulltext It is generally accepted that vocal performance decreases with age. This decrease can be expected to be more pronounced in voice loading professions, which may lead to occupational dysphonia. The aim of this study was to investigate the course of voice complaints, experienced handicap, and absenteeism of work due to voice problems throughout the teaching years. Questionnaires were distributed among teachers of primary and secondary education, and 1875 were analyzed. The questionnaire was designed in such a way that personal aspects and questions about periods with symptoms and absence from work were included. The Voice Handicap Index (VHI) developed by Jacobson et al was sent along with the questionnaire. Surprisingly, a significant decrease of voice complaints during the career of the teachers was observed. The expectation that the percentage of teachers with a history of voice problems should experience more psychosocial impact, measured with the VHI, along their professional career could not be confirmed by this study. These results indicate that serious attention has to be paid to teachers with voice complaints. The fact that teachers in the beginning of their career complain more than in the end of their career emphasizes the importance of adequate aimed prevention programs for future teachers and for starting teachers with regard to their voice.

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 : 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.

Contains fulltext : 53706.pdf (Publisher’s version ) (Closed access) BACKGROUND: Continuous positive airway pressure (CPAP) increases the caudad spread of sensory blockade after low-thoracic epidural injection of lidocaine. We hypothesized that CPAP would increase cephalad spread of blockade after cervicothoracic epidural injection. METHODS: Twenty patients with an epidural catheter at the C6-7 or C7-T1 interspace received an epidural dose of lidocaine while breathing at ambient pressure (control group), or while breathing with 7.5 cm H2O CPAP. After injection, we evaluated the spread of sensory blockade. Spirometry variables before and after epidural injection were also measured. RESULTS: Data are presented as median (interquartile range) values. Sensory block ranged from C7 (C4-7) to T4 (T4-6) in the control group and from C2 (C2-4) to T4 (T2-5) in the CPAP group (P = 0.003 for the cranial border). The total number of segments blocked was 7.5 (6.8-9.8) in the control group and 10 (8-12) in the CPAP group (P = 0.13). The number of segments blocked cranial to the injection site was one (0.8-3.5) in the control group and five (3.5-7) in the CPAP group (P = 0.006). The number of patients with a maximal cranial block (up to C2) was one in the control group and seven in the CPAP group (P = 0.02). In both groups, there was a small but significant decrease from baseline in spirometry values, with no differences between groups. CONCLUSION: Applying CPAP during cervicothoracic epidural injection of lidocaine resulted in a more cranial extension of sensory blockade when compared with breathing at ambient pressure.

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.

A cross-sectional questionnaire survey was done among 457 female student teachers and 144 females in the general population. The conclusions are based on the opinions of student teachers and the general population. The results of this study show that 39.6% of the student teachers and 32.6% of the general population reported voice complaints at the moment and/or over the past year (p = 0.198). The association between various risk factors (vocal loading factors, physical factors, environmental factors and psycho-emotional factors) and voice complaints were examined. Vocal load was reported in both the student teachers and the general population (p = 0.322). Among the subjects with voice complaints, the student teachers were significantly more of the opinion than the general population that environmental irritants in the classroom (p = 0.001) and the composition of the group they communicate with (p = 0.033) have a negative influence on their voice. In the groups with voice complaints, the student teachers reported significantly less than the general population that stress (p = 0.004) and the deterioration of their general physical condition (p = 0.003) have a negative influence on their voice. Remarkably, over a third of the student teachers and one fifth of the general population with voice complaints were of the opinion that decrease of hearing has a negative influence on their voices (p = 0.113). There was no significant difference in Voice Handicap Index (VHI) scores (p = 0.284) and impact of voice complaints among student teachers and the general population. Over 15% of the student teachers and the general population with voice complaints reported being or having been disabled due to the voice problem, probably reflecting the severity of the voice problem (p = 0.838). The groups reporting voice complaints and disability in relation to their voice complaints have significantly higher VHI scores than those without voice complaints and disability, which indicates a higher psychosocial impact of voice complaints. Only around a third of the student teachers and the general population with voice complaints sought paramedical care (p = 0.656)/treatment (p = 0.361) for their voice complaint. Only a minority of student teachers (18.6%) and the general population (29.5%) with voice complaints were of the opinion that the number of people they communicate with has a negative influence on their voice (p = 0.120). Only around a third of the student teachers and less than a tenth of the general population with voice complaints were of the view that they would develop a voice complaint due to their profession (p = 0.003). Less than half of the student teachers and less than one fifth of the general population with voice complaints were aware of the potential risks of their profession on their voice (p = 0.002). Voice complaints appear to have a multifactorial genesis. The student teachers are not sufficiently aware of the impact of the various risk factors on their voice. Furthermore, they are not aware of the potential risk that future teaching may have on their voice. This apparent lack of awareness in student teachers may be considered a risk factor for voice complaints.

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 : 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 : 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.

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 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.

Contains fulltext : 50306.pdf (Publisher’s version ) (Closed access) PURPOSE: To test human CRB1 heterozygotes for possible clinical or functional retinal changes and to evaluate whether a patient with Leber congenital amaurosis (LCA) with CRB1 mutations not consistent with previously described CRB1 phenotypes carried a modifier allele in another LCA gene. METHODS: Seven unrelated heterozygous carriers of CRB1 mutations underwent phenotyping by full eye examinations (indirect ophthalmoscopy and slit lamp biomicroscopy) and functional testing (standard full-field electroretinography [ERG] and multifocal ERG). For genotyping of the LCA patients and their parents, denaturing high-performance liquid chromatography (dHPLC) analyses were performed, followed by sequence analysis of CRB1, followed by sequence analysis of the AIPL1 and CRX genes to identify a putative modifier effect in a patient with an atypical CRB1 phenotype. RESULTS: Reduced full-field ERG b-wave amplitudes were observed with scotopic -2 dB flash (140 microV; P < 0.05), normal full-field cone ERGs, and significant regional retinal dysfunction on mfERG in five of seven carriers of CRB1 mutations. A known AIPL1 mutation (p. R302L) was identified as a potential modifier allele in a patient with LCA carrying two CRB1 mutations and with a prominent maculopathy. CONCLUSIONS: In human heterozygotes of CRB1 mutations (parents of offspring with LCA), distinctive regional retinal dysfunctions were found by multifocal ERG measurements that were consistent with the focal histologic abnormalities reported for the two CRB1 knockout mice models. This phenotypic finding may identify CRB1 carriers and point to the causal gene defect in affected LCA offspring, significantly facilitating the molecular diagnostic process. Evidence suggests a modifier allele in AIPL1 in a patient with LCA with prominent atrophic macular lesions and homozygous defects in CRB1.

Contains fulltext : 47623.pdf (Publisher’s version ) (Closed access) OBJECTIVES: To perform genetic analysis and to analyze cochleovestibular impairment features in a newly identified Dutch family with nonsyndromic autosomal dominant hearing impairment (DFNA9). STUDY DESIGN: Genetic analysis was performed using microsatellite markers and single nucleotide polymorphisms. Audiometric data were collected and analyzed longitudinally. Results were compared with those obtained in previously identified P51S COCH mutation carriers (n = 74). Special attention was also given to a comparison of age-related features such as progressive hearing loss and vestibular impairment. SETTING: Tertiary referral center. PATIENTS: G88E COCH mutation carriers from a Dutch family. MAIN OUTCOME MEASURES: The study of clinical features of a DFNA9 family carrying a G88E COCH mutation and to compare this to the symptoms of those carrying a P51S/COCH mutation. RESULTS: Pure-tone thresholds, phoneme recognition scores, and vestibular responses of the G88E mutation carriers were essentially similar to those previously established in the P51S mutation carriers. Hearing started to deteriorate in G88E mutation carriers from age 46 to 49 years and onward, whereas deterioration of vestibular function started from approximately age 46 years. In the P51S mutation carriers, vestibular impairment started earlier, at approximately age 34 years. However, the difference in age of onset with the G88E mutation carriers was not significant. Remarkably, the proportion of patients who developed complete vestibular areflexia within the age range of 40 to 56 years was significantly lower for the G88E mutation carriers than for the P51S mutation carriers. CONCLUSION: Apart from a significantly lower frequency of vestibular areflexia between the ages of 40 and 56 years, there are no phenotypic differences between carriers of the G88E and P51S mutations in the COCH gene.

Contains fulltext : 47349.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To study the effect of two multipolar electrode configurations on speech perception, pitch perception, and the intracochlear electrical field. STUDY DESIGN: Crossover design; within subject. SETTING: Tertiary referral center. PATIENTS: Eight experienced adult cochlear implant users. INTERVENTION: Each subject used each of three experimental processors for 3 weeks. The following processors were compared that differed only in electrode configuration: 1) monopolar; 2) hybrid quadrupolar, in which half of the current returned to the extracochlear reference electrode and half to two electrodes immediately to the left and right of the active electrode; and 3) flat tripolar +2, which directed all the current to four reference electrodes (two on each side), separated from the active electrode by two inactive electrodes. All the processors used the standard Advanced Bionics HiRes speech-processing strategy, 12 channels, 1,220 pulses per second per channel, and with a pulse width of 33 (micros/phase). RESULTS: The monopolar processors had the largest stimulation efficiency and the smallest dynamic range in linear current units. The reverse was true of flat tripolar +2 processor, whereas the hybrid quadrupolar processor fell in between. Insufficient loudness growth prevented the use of the flat tripolar +2 processor in three subjects. Word recognition did not differ between the clinically used 16-channel monopolar processor and the experimental monopolar processor, regardless of the differences in the number of channels, pulse rate, and duration of experience. Word recognition with the flat tripolar +2 processor was significantly poorer than with the monopolar and hybrid quadrupolar processors; monopolar and quadrupolar processors did not differ. There was no significant interaction between processor type and competing noise type (stationary or fluctuating), but performance at the higher level of fluctuating noise was best with the hybrid quadrupolar processor in almost all the subjects. Pitch scaling showed ceiling performance in five subjects and differed between processors in the two other subjects with imperfect tonotopy. Intracochlear current spread was considerable with the monopolar configuration; it was reduced with the hybrid quadrupolar configuration and virtually absent beyond the active electrodes with the tripolar configuration. CONCLUSION: More confined configurations reduced the longitudinal width of the electrical field, which was expected to enhance channel separation, but no improvement in word recognition was found. More research is needed to test confined configurations that have enhanced efficiency and to evaluate the fundamental effects of configuration on channel discriminability.

OBJECTIVE: To evaluate the safety and performance of a synthetic dural sealant as an adjunct to standard surgical dural repair techniques to prevent cerebrospinal fluid (CSF) leakage. METHODS: This study was designed as a prospective, nonrandomized, single-center clinical trial. The dural sealant is a synthetic absorbable hydrogel. Consecutive series of patients scheduled for elective cranial and intradural spinal surgery were included until a total of 50 applications were achieved. It was used primarily as an adjunct to ensure watertight dural closure. The end point was defined as no leak with the Valsalva maneuver after dural sealant application. The patients were followed up for 3 months after surgery to check for CSF leakage, standard laboratory and neurological examinations, and possible adverse advents. RESULTS: Of the 49 patients, 46 were included and treated with the dural sealant because of spontaneous leak (n = 34; 69%) or leak after the Valsalva maneuver (n = 12; 25%). There was no leak in the other patients (n = 3; 6%). After application of the dural sealant, there was no leak in all 46 patients (100%). Of the 46 patients included, there was one case of overt CSF leak. One patient had a pseudomeningocele. There were no adverse events other than those related to the disease or to the surgical procedure itself. CONCLUSION: The dural sealant, a synthetic absorbable hydrogel, is a useful adjunct to achieve watertight dural closure. Application resulted in 100% closure of intraoperative CSF leaks. There are no evident adverse effects.

Item does not contain fulltext OBJECTIVE: To study the impact of introducing a blood loss chart as a means to support treatment selection in women with dysfunctional uterine blood loss. STUDY DESIGN: Retrospective chart review, prospective observational study, and decision modelling. RESULTS: Introduction of a blood loss chart resulted in a 50% reduction of re-treatments within 1 year (from 25% to 12.5%). The use of the blood loss chart resulted in a slightly higher expected value and lower costs, which is reflected in a more favourable cost/quality adjusted life year (QALY) ratio. CONCLUSION: The use of a blood loss chart as an aid in treatment selection in women with dysfunctional uterine blood loss is feasible. Although its use requires an extra outpatient visit, the associated extra costs are off-set by its impact on initial treatment selection, and, in particular, on the probability of re-treatment within 1 year of follow-up.

Contains fulltext : 47504.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To identify EEG derivations that yield high signal-to-noise ratios (SNRs) of the auditory steady-state response (ASSR) in infants aged 0 to 5 months. DESIGN: The ASSR was recorded simultaneously from 10 EEG derivations in a monopolar montage in 20 sleeping infants. Stimuli were tones of 0.5 or 2 kHz that were 100% amplitude modulated and 20% frequency modulated, presented at 65 dB SPL for 4.4 minutes in either the right or the left ear. An amplitude modulation frequency of 90 Hz (left ear) or 94 Hz (right ear) was used. From the 10 measured monopolar derivations, all 45 bipolar derivations were calculated mounting up to 55 EEG derivations. EEG derivations were selected in the preferred set if they had the largest SNRs within subjects and if they were obtained significantly more frequently across subjects than was expected by chance (Monte Carlo simulation and Wilcoxon signed ranks test). RESULTS: The preferred derivations are both mastoids ipsilateral to the stimulated ear with Cz as common reference. These derivations improved SNRs compared with each of several conventional EEG derivations (excluding the preferred derivations) between 16 and 69% (500 Hz, left ear), 9 and 132% (500 Hz, right ear), 31 and 193% (2 kHz, left ear), and 3 and 105% (2 kHz, right ear). In contrast to results reported earlier for adults, high SNRs were not found at the inion-Cz derivation in these infants. CONCLUSIONS: High SNRs were obtained in infants aged younger than 6 months if the ASSR was recorded from the mastoids ipsilateral to the ear of stimulation referenced to Cz.

Contains fulltext : 47792.pdf (Publisher’s version ) (Closed access) Nail-patella syndrome (NPS) is characterized by developmental defects of dorsal limb structures, nephropathy, and glaucoma and is caused by heterozygous mutations in the LIM homeodomain transcription factor LMX1B. In order to identify possible genotype-phenotype correlations, we performed LMX1B mutation analysis and comprehensive investigations of limb, renal, ocular, and audiological characteristics in 106 subjects from 32 NPS families. Remarkable phenotypic variability at the individual, intrafamilial, and interfamilial level was observed for different NPS manifestations. Quantitative urinanalysis revealed proteinuria in 21.3% of individuals. Microalbuminuria was detected in 21.7% of subjects without overt proteinuria. Interestingly, nephropathy appeared significantly more frequent in females. A significant association was established between the presence of clinically relevant renal involvement in an NPS patient and a positive family history of nephropathy. We identified normal-tension glaucoma (NTG) and sensorineural hearing impairment as new symptoms associated with NPS. Sequencing of LMX1B revealed 18 different mutations, including six novel variants, in 28 families. Individuals with an LMX1B mutation located in the homeodomain showed significantly more frequent and higher values of proteinuria compared to subjects carrying mutations in the LIM domains. No clear genotype-phenotype association was apparent for extrarenal manifestations. This is the first study indicating that family history of nephropathy and mutation location might be important in precipitating individual risks for developing NPS renal disease. We suggest that the NPS phenotype is broader than previously described and that NTG and hearing impairment are part of NPS. Further studies on modifier factors are needed to understand the mechanisms underlying phenotypic heterogeneity.

Contains fulltext : 49086.pdf (Publisher’s version ) (Closed access) We used quantitative sensory testing (QST) to gain further insight into mechanisms underlying pain in CRPS 1. Specific goals were: (1) to identify altered patterns of sensory processing some 8 years after diagnosis, (2) to document differences in sensory processing between 'warm' and 'cold' diagnostic subgroups, (3) to determine relationships between changed sensory processing and disease progression regarding pain. The study was performed on a cohort of patients (n=47) clinically diagnosed with CRPS 1 of one upper extremity approximately 8 years previously. Pain was quantified by VAS and MacGill Pain Questionnaire (MPQ), and all subjects underwent electrical and mechanical QST. Cold patients (n=13) had poorer MPQ scores than warm ones (n=34), and more pain on electrical stimulation. Their evoked pain increased with disease progression and correlated with clinical pain measures. For both diagnostic subgroups, thresholds to pressure pain were lower on the affected extremity and with disease progression. Eight years after original diagnosis, cold CRPS 1 patients have poorer clinical pain outcomes and show persistent signs of central sensitisation correlating with disease progression. The latter is not the case for warm CRPS 1 patients. Both diagnostic subgroups show greater pressure hyperalgesia on the affected limb and with disease progression. QST may prove useful in the subdiagnosis of CRPS 1 and in quantifying its progression, with both applications warranting further investigation for clinical and research use.

Contains fulltext : 47759.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Despite the identification of mutations in the connexin 26 (GJB2) gene as the most common cause of recessive nonsyndromic hearing loss, the pattern of hearing impairment with these mutations remains inconsistent. Recently a deletion encompassing the GJB6 gene was identified and hypothesized to also contribute to hearing loss. We hereby describe the hearing impairment in Dutch patients with biallelic connexin 26 (GJB2) and GJB2+connexin 30 (GJB6) mutations. METHODS: The audiograms of patients who were screened for GJB2 and GJB6 mutations were analysed retrospectively. Standard statistical testing was done for symmetry and shape, while repeated measurement analysis was used to assess the relation between mutation and severity. Progression was also studied via linear regression analysis. RESULTS: Of 222 hearing-impaired individuals, 35 exhibited sequence variations; of these 19 had audiograms for study. Hearing loss in patients with biallelic "radical" (i.e. deletions, nonsense and splice site) mutations was significantly worse than in the wild type and heterozygotes (SAS proc GENMOD, p=0.013). The presence of at least one missense mutation in compound heterozygotes tends to lead to better hearing thresholds compared to biallelic radical mutations (p=0.08). One patient with the [35delG]+[del(GJB6-D13S1830)] genotype was severely impaired. Non-progressive hearing impairment was demonstrated in five 35delG homozygotes in individual longitudinal analyses. However a patient with the [299A>C]+[416G>A] genotype showed significant threshold progression in the lower frequencies. Findings on asymmetry and shape were inconclusive. CONCLUSIONS: Our data support the hypothesis that severity is a function of genotype and its effect on the amino acid sequence. A bigger cohort is required to establish non-progressivity more definitively.

Contains fulltext : 48525.pdf (Publisher’s version ) (Open Access) The results obtained by percutaneous cervical cordotomy (PCC) were analysed in 43 terminally ill cancer patients treated in our institution from 1998 to 2001. We wished to determine whether there is still a place for PCC in the actual clinical situation with its wide choice of pain therapies. All patients had severe unilateral pain due to cancer, resistant to opioids and co-analgesics. Following PCC, mean pain intensity was reduced from Numeric Rating Scale (NRS) 7.2 to 1.1. At the end of life, pain had increased to NRS 2.9. Initially following PCC a good result (NRS

Item does not contain fulltext PURPOSE: To report unusual vitelliform fundus findings in three cases of paraneoplastic retinopathy associated with metastasised cutaneous or uveal melanoma and in one case, a unique immunoreactivity response. PATIENTS AND METHODS: Observational case series. The histories of three patients with MAR-like paraneoplastic retinopathy were reviewed. Electroretinography, Goldmann perimetry, fluorescein angiography, and in one case optical coherence tomography, immunohistochemistry and Western blotting were performed. RESULTS: All patients revealed similar paraneoplastic vitelliform retinal abnormalities. Symptoms in two cases differed from the classical MAR syndrome. In one case, western blotting and immunohistochemistry demonstrated antibodies against 120-kDa, a soluble photoreceptor protein. No immunoreactivity to retinal bipolar cells was detected. CONCLUSION: The clinical, electrophysiological, and immunological findings in our patients suggest a melanoma associated paraneoplastic origin, like in MAR syndrome. However contrary to MAR syndrome, this paraneoplastic vitelliform retinopathy exhibits a peculiar fundus picture, consisting of serous macular detachment and nummular vitelliform lesions in the posterior pole. This could be an unusual presentation of MAR or a separate paraneoplastic entity.

Contains fulltext : 48927.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To present the course of tympanic membrane pathology in childhood and young adulthood after otitis media (OM) in early life. STUDY DESIGN: Prospective follow-up study. SETTING: Community study of a birth cohort. PATIENTS: Three hundred fifty-eight subjects with a positive and negative history of OM (OM+ or OM-) or ventilation tube insertion (VT+ or VT-) derived from a birth cohort that had been followed-up from preschool to adult age. METHODS: Standardized otomicroscopic examination performed at ages 8 and 18 years. MAIN OUTCOME MEASURES: Tympanic membrane abnormalities (i.e., tympanosclerosis, atrophy, atelectasis and retraction pockets of the pars tensa, and retraction of the pars flaccida). RESULTS: At the age of 8 years, tympanic membrane pathology was highly prevalent in the both OM+ subcohorts (OM+VT+, 92% and OM+VT-, 46%), whereas in the OM- ears (11%), tympanic membrane abnormalities were rare. In the subsequent 10-year period, many tympanic membrane abnormalities disappeared spontaneously, although the prevalence of tympanosclerosis remained substantial in the OM+VT+ cohort. CONCLUSION: The natural course of most tympanic membrane pathology associated with OM in early life is favorable over time, suggesting an intrinsic repair capacity of the tympanic membrane. Tympanosclerosis, the most prevalent sequelae of OM and treatment with VT, however, shows little tendency of resolution.