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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.

Item does not contain fulltext OBJECTIVE: To investigate whether Helicopter-Mobile Medical Teams (H-MMTs or HEMS) are optimally deployed in all emergency dispatch centres. DESIGN: Descriptive, retrospective. METHOD: Initially, we assessed whether data from different ambulance regions could be compared effectively if they were related to the number of inhabitants per region. Data concerning the number of inhabitants, number of deaths caused by trauma, number of traffic accidents with injury, number ofemergency call-outs by ambulance services and H-MMT deployment were collected from several governmental databases for the period 2002-2005. The correlation coefficients between these data and the number of inhabitants were calculated. Subsequently, we determined the number of H-MMT deployments per 100,000 inhabitants per year per emergency dispatch centre. The number of H-MMT dispatches from the 4 H-MMT coordinating dispatch centres was compared to the number of dispatches from the 17 other emergency dispatch centres. RESULTS: There was a strong correlation between the number of deaths caused by trauma, the number of traffic accidents with injury, emergency call-outs from ambulance services, and the number of inhabitants per region (correlation coefficients: 0.90-0.98). On average there were 2664 H-MMT calls per year. The average number of H-MMT calls per emergency dispatch centre per year was 110 (range: 2-403). The number of H-MMT deployments per 100,000 inhabitants per year was 10.5 (0.9-27.8). Emergency dispatch centres coordinating H-MMTs conducted significantly more H-MMT calls with a lower cancellation rate. CONCLUSION: By relating the deployment of H-MMTs with the number of inhabitants per region, a comparison can be made of the deployment frequencies in different emergency dispatch regions. The deployment of H-MMTs proved to differ significantly between emergency dispatch centres.

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 : 70836.pdf (Publisher’s version ) (Closed access) The Baha (bone-anchored hearing aid) Softband appears to be an effective mean of hearing rehabilitation for children with a congenital bilateral aural atresia who are too young for the amplification of a Baha on an implant. The aided hearing threshold with a Baha Softband is almost equal to that achieved with a conventional bone conductor. The speech development of the children studied with a Baha Softband is on a par with peers with good hearing.

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Contains fulltext : 69300.pdf (Publisher’s version ) (Closed access) BACKGROUND: Fundus autofluorescence (FAF) may be excited and measured at different wavelengths. In the present study we compared short wavelength and near-infrared FAF patterns of retinal dystrophies. METHODS: We analysed both eyes of 108 patients with diverse retinal dystrophies. Besides colour fundus photographs, FAF images were obtained with the Heidelberg Retina Angiograph (HRA 2). Excitation wavelengths of 488 nm (blue; filter at 500 nm) and 787 nm (near-infrared; filter at 810 nm) were applied. For improvement of the signal-to-noise ratio a total of nine images were averaged, and the mean images (original grey values, not normalized) were analysed. RESULTS: Useful FAF images of both excitation wavelengths were achieved in all patients. We observed characteristic FAF patterns, which differed between excitation wavelengths depending on the disease. With time, FAF pattern changes and progression could be observed. CONCLUSION: FAF of both wavelengths provided additional information for phenotype description in retinal dystrophies. Other than short wavelength FAF, near-infrared FAF showed different pathological changes, which may be related to changes in RPE melanin. However, any conclusions may be limited by the still incomplete knowledge about the prognostic value of FAF in the diseases studied here.

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.

Item does not contain fulltext We describe thoracic spinal stenosis with progressive myelopathy in association with Albright hereditary osteodystrophy (AHO) in a 12-year-old child with delayed diagnosis and review the relevant literature in order to identify the pathophysiological mechanism. The child was successfully treated by decompressive upper thoracic laminoplasty with full neurological recovery. The pathological changes of the skin also dissolved. Ten more cases of myelopathy and paraparesis in association with AHO, of whom two were children, could be found in the literature. Basically, two different causes for the spinal canal stenosis could be identified: abnormal ossifications of ligaments and congenital narrow spinal canal due to short vertebral pedicles. Awareness of structural spinal column changes in AHO is essential in order to appreciate the neurological symptoms of a beginning myelopathy before irreversible damage to the myelum occurs.

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 : 69446.pdf (Publisher’s version ) (Closed access) BACKGROUND: The sciatic nerve block by the posterior approaches represents one of the more difficult ultrasound-guided nerve blocks. Our clinical experiences with these blocks indicated a point slightly distal to the subgluteal fold as an advantageous position to allow good ultrasonic visibility. In this study, we systematically scanned the sciatic nerve from the subgluteal fold to the popliteal crease, to determine an optimal point for ultrasonographic visualization. METHODS: After institutional approval and written informed consent, we recruited 15 volunteers to visualize the sciatic nerve from the subgluteal fold to the popliteal crease using a linear ultrasound probe in the range of 7-13 MHz. The ultrasonographic visibility of the sciatic nerve, nerve diameter (width and thickness), and skin-to-nerve distance at 20 equidistant points between the subgluteal fold and the popliteal crease were recorded. RESULTS: The sciatic nerve could be successfully visualized in cross-section as a hyperechoic structure on ultrasound in all volunteers. In the course from subgluteal to the popliteal area, the shape of the sciatic nerve changed from flat to round, while the skin-nerve distance varied with the smallest skin-nerve distances at the popliteal crease and at 5.4 cm (on average) distal to the subgluteal fold. The best ultrasonographic visibility scores were found between 7.2 and 10.8 cm (on average) distal to the gluteal fold. CONCLUSION: Between 5.4 and 10.8 cm from the subgluteal fold seems to be the best area to scan the sciatic nerve in terms of superficial nerve position and good ultrasonic visibility.

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 : 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 : 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.

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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 : 70096.pdf (Publisher’s version ) (Closed access)

Contains fulltext : 69239.pdf (Publisher’s version ) (Closed access) In this in vitro study, a needle guidance device and a 'free hand' technique for ultrasound guided needle insertion were compared in a simulated ultrasound-guided interventional task using a porcine phantom. Residents inexperienced in using ultrasonography were asked to insert a needle, using an in-plane techniques, and to make contact with metal rods at a depth of 2 and 4 cm in the phantom. The transducer made angles of 90 degrees, 60 degrees and 45 degrees with the surface of the phantom. The times to perform the procedures were significantly shorter and the needle visualisation was significantly better when using the needle guidance device. The residents ranked their satisfaction with the needle-guidance device significantly better than the 'free-hand' technique. This device may be beneficial when performing ultrasound guided peripheral nerve blocks, especially by inexperienced operators.

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 : 53571.pdf (Publisher’s version ) (Closed access) The highly ordered distribution of neurons is an essential feature of a functional mammalian retina. Disruptions in the apico-basal polarity complexes at the outer limiting membrane (OLM) of the retina are associated with retinal patterning defects in vertebrates. We have analyzed the binding repertoire of MPP5/Pals1, a key member of the apico-basal Crumbs polarity complex, that has functionally conserved counterparts in zebrafish (nagie oko) and Drosophila (Stardust). We show that MPP5 interacts with its MAGUK family member MPP1/p55 at the OLM. Mechanistically, this interaction involves heterodimerization of both MAGUK modules in a directional fashion. MPP1 expression in the retina throughout development resembles the expression of whirlin, a multi-PDZ scaffold protein and an important organizer in the Usher protein network. We demonstrate that both proteins interact strongly by both a classical PDZ domain-to-PDZ binding motif (PBM) mechanism, and a mechanism involving internal epitopes. MPP1 and whirlin colocalize in the retina at the OLM, at the outer synaptic layer and at the basal bodies and the ciliary axoneme. In view of the known roles of the Crumbs and Usher protein networks, our findings suggest a novel link of the core developmental processes of actin polymerization and establishment/maintenance of apico-basal cell polarity through MPP1. These processes, essential in neural development and patterning of the retina, may be disrupted in eye disorders that are associated with defects in these protein networks.

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 : 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.

Contains fulltext : 34519.pdf (Publisher’s version ) (Closed access) Myosin XVA is an unconventional myosin which has been implicated in autosomal recessive nonsyndromic hearing impairment (ARNSHI) in humans. In Myo15A mouse models, vestibular dysfunction accompanies the autosomal recessive hearing loss. Genomewide homozygosity mapping and subsequent fine mapping in two Turkish families with ARNSHI revealed significant linkage to a critical interval harboring a known deafness gene MYO15A on chromosome 17p13.1-17q11.2. Subsequent sequencing of the MYO15A gene led to the identification of a novel missense mutation, c.5492G-->T (p.Gly1831Val) and a novel splice site mutation, c.8968-1G-->C. These mutations were not detected in additional 64 unrelated ARNSHI index patients and in 230 Turkish control chromosomes. Gly1831 is a conserved residue located in the motor domains of the different classes of myosins of different species. Molecular modeling of the motor head domain of the human myosin XVa protein suggests that the Gly1831Val mutation inhibits the powerstroke by reducing backbone flexibility and weakening the hydrophobic interactions necessary for signal transmission to the converter domain. Copyright (c) 2007 Wiley-Liss, Inc.

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.

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

Using in situ schlieren microscopy, we have studied the growth process of nickel sulfate hexahydrate crystals in a gradient magnetic field under conditions where convection is suppressed, to investigate whether the features that occur here are the same as those that occur during microgravity crystal growth. An expansion of the depletion zone with decreasing effective gravity was observed. If convection is suppressed, the depletion zone keeps expanding and the crystal growth rate decreases significantly, reaching a constant value. Although there remains some residual flow, it is very slow and does not affect the depletion zone. We find that homogeneity of the effective gravity in the milligravity range is sufficient to suppress convection. The results show that crystal growth in gradient magnetic fields is a good alternative for microgravity crystal growth in space.

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.

Contains fulltext : 49510.pdf (Publisher’s version ) (Closed access)

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.