Mid-term quality of life after gastric band removal and single-stage conversion to gastric bypass: a single-center cohort study.

BACKGROUND: Revision surgeries in patients with failed gastric banding including band removal are increasingly necessary. However, long-term outcomes after band removal alone are unsatisfactory due to weight regain and limited improvement in quality of life. This study aimed to report mid-term quality of life outcomes after gastric band removal and single-stage conversion to Roux-en-Y gastric bypass. METHODS: Data of 108 patients who underwent conversion surgery from 2011 to 2017 were extracted from a prospective database and retrospectively analyzed. During follow-up visits, physical and laboratory data as well as quality of life questionnaires were obtained. RESULTS: Postoperative mean Moorehead score increased significantly after 1 year (1.62 ± 0.86, p < 0.001) and after 5 years (1.55 ± 0.84, p < 0.001) compared to baseline values (0.72 ± 1.1). The mean follow-up time was 53 months. Moorehead scores at 1, 2, and 5 years postoperative were available in 75% (n = 81), 71% (n = 77), and 42% (n = 45) of cases, respectively. Mixed ANOVA analysis showed a significantly superior increase in Moorehead score in males (p = 0.024). No other significant predictors were identified. Lasting BMI reduction (- 4.6 to 33.0 ± 6.7 kg/m2, p < 0.001) and weight loss (- 12.9% (- 13.6 kg), p < 0.001) 5 years after conversion surgery were seen. Postoperative complications occurred in 35% (n = 38) of patients with a re-operation rate of 30.5% (n = 33). CONCLUSION: The current study shows that band removal with single-stage gastric bypass in patients with failed gastric banding leads to a lasting improvement in quality of life and may be the rescue procedure of choice in this setting.

Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebellopontine angle (CPA), 1a transotic including the CPA, and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients decided for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single-stage procedure; 1 patient had extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI after repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontine angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Cochlear implantation during or after tumor resection (i. e., as synchronous or staged surgeries) is an option for hearing rehabilitation in cartain cases and represents a therapeutic approach in contrast to a "wait-and-test-and-scan" strategy.

[Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants. German version]. / Intralabyrinthäre Schwannome : Chirurgisches Management und Hörrehabilitation mit Cochleaimplantaten.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebello-pontine angle (CPA), 1 a transotic including the CPA and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients opted for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single stage procedure; 1 patient received extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI following repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontile angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Provided performed early enough, cochlear implantation after surgical removal of ILS is an option for auditory rehabilitation, thus representing-in contrast to the "wait-and-test-and-scan" strategy-a therapeutic approach.

[Personalized molecular medicine: new paradigms in the treatment of cochlear implant and cancer patients]. / Molekulare personalisierte Medizin: Paradigmenwechsel in der Krankenversorgung von Cochlear-Implant- und Tumorpatienten.

OBJECTIVES: To evaluate present options for the indication of cochlear implants (CI) and new forms of treatment for head and neck cancer, melanomas and basal cell carcinomas, with emphasis on future perspectives. METHODS: A literature search was performed in the PubMed database. Search parameters were "personalized medicine", "individualized medicine" and "molecular medicine". RESULTS: Personalized medicine based on molecular-genetic evaluation of functional proteins such as otoferlin, connexin 26 and KCNQ4 or the Usher gene is becoming increasingly important for the indication of CI in the context of infant deafness. Determination of HER2/EGFR mutations in the epithelial growth factor receptor (EGFR) gene may be an important prognostic parameter for therapeutic decisions in head and neck cancer patients. In basal cell carcinoma therapy, mutations in the Hedgehog (PCTH1) and Smoothened (SMO) pathways strongly influence the indication of therapeutic Hedgehog inhibition, e.g. using small molecules. Analyses of c-Kit receptor, BRAF-600E and NRAS mutations are required for specific molecular therapy of metastasizing melanomas. The significant advances in the field of specific molecular therapy are best illustrated by the availability of the first gene therapeutic procedures for treatment of RPE65-induced infantile retinal degradation. CONCLUSION: The aim of personalized molecular medicine is to identify patients who will respond particularly positively or negatively (e.g. in terms of adverse side effects) to a therapy using the methods of molecular medicine. This should allow a specific therapy to be successfully applied or preclude its indication in order to avoid serious adverse side effects. This approach serves to stratify patients for adequate treatment.

[Image guiding techniques and navigation for TACE, SIRT and TIPS]. / Bildführungstechniken und Navigation bei TACE, SIRT und TIPS.

CLINICAL/METHODICAL ISSUE: To avoid non-targeted embolization in liver tumors, arteries important for embolization must be detected. In transarterial chemoembolization (TACE) arteries for particle embolization have to be detected and in selective internal radiotherapy (SIRT) extrahepatic arteries which must be protected from embolization have to be detected. In transjugular intrahepatic portosystemic shunt (TIPS) the problem is to achieve an exactly targeted puncture of the portal vein. STANDARD RADIOLOGICAL METHODS: In TACE and SIRT detection of the vessels is performed from various angles by digital subtraction angiography (DSA). In TIPS puncture is guided by ultrasound or performed blindly. METHODICAL INNOVATIONS: Using cone beam CT (CBCT) very small vessels in the liver can be visualized and 2D-3D back projection is able to detect the exact position of the portal vein in TIPS. ACHIEVEMENTS: The use of CBCT and 2D-3D back projection significantly enhances navigation of vessels. PRACTICAL RECOMMENDATIONS: If flat detector technique is available CBCT should be used in TACE and SIRT and 2D-3D navigation needs hardware and software updates.

Altered expression of securin (Pttg1) and serpina3n in the auditory system of hearing-impaired Tff3-deficient mice.

INTRODUCTION: Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals. RESULTS: Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots. CONCLUSIONS: We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis.

Lack of pharmacokinetic interaction between dapagliflozin, a novel sodium-glucose transporter 2 inhibitor, and metformin, pioglitazone, glimepiride or sitagliptin in healthy subjects.

AIMS: Dapagliflozin increases urinary glucose excretion by selectively inhibiting renal sodium-glucose transporter 2, an insulin-independent mechanism of action that may be complementary to that of other oral antidiabetes drugs. The current studies assessed the potential for pharmacokinetic (PK) interaction between dapagliflozin and pioglitazone, metformin, glimepiride or sitagliptin in healthy subjects following single-dose administration. METHODS: In open-label, randomized, three-period, three-treatment crossover studies, 24 subjects received 50 mg dapagliflozin, 45 mg pioglitazone or the combination, while 18 subjects received 20 mg dapagliflozin, 1000 mg metformin or the combination. In an open-label, randomized, five-period, five-treatment, unbalanced crossover study, 18 subjects first received 20 mg dapagliflozin, 4 mg glimepiride or the combination, and afterward 100 mg sitagliptin or sitagliptin plus 20 mg dapagliflozin. Blood samples were taken over 72 h of each treatment period. Lack of PK interaction was defined as the ratio of geometric means and 90% confidence interval (CI) for combination:monotherapy being within the range of 0.80-1.25. RESULTS: Co-administration of dapagliflozin with pioglitazone, metformin, glimepiride or sitagliptin had no effect on dapagliflozin maximum plasma concentration (C(max) ) or area under the plasma concentration-time curve (AUC). Similarly, dapagliflozin did not affect the C(max) or AUC for the co-administered drug, except for slight extensions of the 90% CI for the ratio of geometric means for glimepiride AUC (upper limit 1.29) and pioglitazone C(max) (lower limit 0.75). All monotherapies and combination therapies were well tolerated. CONCLUSION: Dapagliflozin can be co-administered with pioglitazone, metformin, glimepiride or sitagliptin without dose adjustment of either drug.

Effect of a high-fat meal on the pharmacokinetics of dapagliflozin, a selective SGLT2 inhibitor, in healthy subjects.

Dapagliflozin is a potent and selective inhibitor of sodium-glucose co-transporter type 2 that is being developed for the treatment of type 2 diabetes mellitus. This open-label, randomized, two-period, two-treatment (single doses of 10-mg dapagliflozin fasted or fed), crossover study was conducted to evaluate the effect of a high-fat meal on the pharmacokinetics of dapagliflozin in 14 healthy subjects. Compared to the fasted state, a high-fat meal decreased mean dapagliflozin maximum plasma concentrations (C(max) ) by 31%, increased the time to C(max) (T(max) ) by 1 h, but did not affect overall dapagliflozin systemic exposure [area under the plasma concentration-time curve (AUC)]. As the cumulative (daily) amount of glucose excreted in the urine induced by dapagliflozin is dependent upon dapagliflozin AUC, the effect of food on dapagliflozin C(max) is unlikely to have a clinically meaningful effect on dapagliflozin's efficacy. On the basis of these findings, dapagliflozin can be administered without regard to meals.

Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus: effects on glycaemic control and body weight.

AIM: Dapagliflozin is a stable, competitive, reversible, and highly selective inhibitor of sodium-glucose co-transporter 2, the major transporter responsible for renal glucose reabsorption. With an insulin-independent mechanism of action, dapagliflozin is currently being developed for the treatment of type 2 diabetes mellitus (T2DM). This work aims to compare the efficacy of dapagliflozin, as measured by the change in hemoglobin A1c concentration (A1c) and body weight, and to determine the pharmacodynamic effects of dapagliflozin, as measured by urinary glucose excretion in early-stage and late-stage T2DM patient populations. METHODS: A total of 151 early-stage patients and 58 late-stage patients with T2DM randomly assigned 10 or 20 mg once daily (QD) dapagliflozin treatment or placebo for 12 weeks from two phase 2 studies were included in the analysis. A1c, body weight, and urinary glucose were compared between the two patient populations. RESULTS: Compared with the early-stage population, patients in the late-stage population had a longer duration of T2DM and higher baseline levels of A1c, body weight, fasting plasma glucose, and urinary glucose excretion. After 12 weeks of dapagliflozin treatment, A1c reduction, weight loss, and increased urinary glucose excretion from baseline were observed in both populations. Baseline A1c level impacted the A1c reduction after dapagliflozin treatment with a comparable effect in patients with early and late stage disease. Late-stage patients had greater reduction in body weight. There was no statistically significant difference in the amount of urinary glucose excretion between the early-stage and late-stage patients. CONCLUSIONS: Dapagliflozin treatment at 10 and 20 mg QD for 12 weeks resulted in significant improvement in glycaemic control and body weight reduction in both early-stage and late-stage patients with T2DM. The findings suggest that dapagliflozin could be a promising treatment option for a wide range of patients with T2DM.

Association of human cathelicidin (hCAP-18/LL-37) gene expression with cardiovascular disease risk factors.

BACKGROUND AND AIMS: Antimicrobial peptides (AMPs) are components of the innate immune system. In addition, evidence suggests that these peptides are associated with various inflammatory diseases. We examined whether expression of the cathelicidin LL-37 in peripheral blood mononuclear cells (PBMCs) is associated with cardiovascular risk factors. METHODS AND RESULTS: A total of 90 men and 87 women selected from STANISLAS cohort were studied. Expression of LL-37 mRNA isolated from PBMCs of these subjects was quantified by quantitative RT-PCR. Anthropometric measurements and biochemical profiles were assessed for each individual. In women, LL-37 mRNA expression was significantly and positively correlated with body mass index (BMI) (p

[Influence of exogenic factors on age-related hearing impairment]. / Einfluss exogener Faktoren auf Altersschwerhörigkeit

BACKGROUND: Age-related hearing impairment is a complex disorder, the causes for which have been insufficiently studied. Genetic and environmental factors all play a role. METHODS: A total of 406 persons aged between 53 and 67 years old were interviewed about various causes and audiometric data were collected. The audiometric pure tone data were adjusted for sex and age and tested for association with exposure to risk factors. RESULTS: Significant negative effects of noise exposure, painkillers, overweight, and cardiovascular diseases on hearing loss were found. A positive effect of moderate alcohol consumption could also be shown in the elderly. These results suggest that a healthy lifestyle can positively affect age-related hearing impairment.

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment.

BACKGROUND: Age-related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4. METHODS: In the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Z(low) and Z(high), representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene-environment and gene-gene interactions. RESULTS: We found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data. CONCLUSION: As replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.

[Disabled elderly people waiting for institutionalization to a hospital ward: prospective study in the administrative district of Strasbourg (France)]. / Personnes âgées dépendantes en attente d'entrée en EHPAD depuis un service hospitalier: étude prospective sur la communauté urbaine de Strasbourg, France.

OBJECTIVES: Our aim was to estimate the number of non-satisfied instutionalization requests for inpatients and to describe the strategies elaborated to compensate for the waiting time. METHODS: This prospective follow-up study concerning all requests for institution admission for inpatients aged 75 years or older hospitalized in acute care and rehabilitation wards. Descriptive data were gathered throughout the social support process conducted during the hospitalization. A three months follow-up was conducted. RESULTS: Among 5200 hospitalizations, a social support process was initiated for 270 patients aged 75 years and over. Two thirds of the sample were women (n=163). Mean age was 82 years. Fifty-two percent of the subjects met the criteria for iso-resource grades (IRG) 1 to 2 and 90% in IRG 1 to 4. The mean length of hospitalized stay (MLOS) was 56.8+/-10.2 days; the MLOS of unjustified stay of 23.5+/-5.6 (n=222). The average time before the social worker was informed of the patient's situation was 13.6+/-2.0 days; in addition, the time required to establish the administrative documents necessary for initiation of the social support progress was 15.0+/-1.8. The principal reasons for social support were physical dependence (77%), mental dependence (60%), insufficient family support (36%) and/or disease progression (21%). At three months, 104 patients were institutionalized, 128 were still on institution waiting list (in hospital: 48%; at home: 16%) and 38 had died (14%). The estimated annual institutional deficit for disabled elderly people was 512 beds. CONCLUSION: In light of demographical perspectives, an overall re-organization of the geriatric network is absolutely necessary. A simple increase in the capacity to fulfil the institutional beds deficit would be insufficient.

[Propionic acidemia and sensorineural hearing loss: is there a connection at the molecular genetics level?]. / Propionazidämie und Schallempfindungsschwerhörigkeit: Gibt es eine molekulargenetische Basis?

CURRENT KNOWLEDGE: Propionic acidemia is caused by a gene defect leading to malfunction of the enzyme propionyl-CoA carboxylase (PCC) and in turn to a pathologic accumulation of propionic acid. Many mutations have been found at the molecular genetic level over the past 20 years, and their implications for the limitation of enzyme activity of PCC in propionic acidemia are discussed. SCIENTIFIC QUESTION AND AIMS OF THE STUDY: As an elevated incidence of deafness has been observed in patients with propionic acidemia, the question arises of whether mutations primarily responsible for this disease could also be the underlying cause for a genetic form of deafness. METHODS AND RESULTS: As well as a standard pure tone audiogram, a pedigree was elaborated and DNA isolated for each family concerned. In one family several subjects displayed mutations of both the PCCA and the PCCB -subunits; these included only one girl whose phenotype was affected, however. CONCLUSIONS: Mutation of the PCCB subunit p.R113X has not previously been mentioned in the literature. According to our present knowledge no connection can be assumed between either of the two mutations and the severe sensorineural hearing loss.

Familial aggregation of tinnitus: a European multicentre study.

INTRODUCTION AND AIM: Tinnitus is a common condition affecting approximately 20% of the older population. There is increasing evidence that changes in the central auditory system following cochlear malfunctioning are responsible for tinnitus. To date, few investigators have studied the influence of genetic factors on tinnitus. The present report investigates the presence of a familial effect in tinnitus subjects. METHODS: In a European multicentre study, 198 families were recruited in seven European countries. Each family had at least 3 siblings. Subjects were screened for causes of hearing loss other than presbyacusis by clinical examination and a questionnaire. The presence of tinnitus was evaluated with the question "Nowadays, do you ever get noises in your head or ear (tinnitus) which usually last longer than five minutes". Familial aggregation was tested using three methods: a mixed model approach, calculating familial correlations, and estimating the risk of a subject having tinnitus if the disorder is present in another family member. RESULTS: All methods demonstrated a significant familial effect for tinnitus. The effect persisted after correction for the effect of other risk factors such as hearing loss, gender and age. The size of the familial effect is smaller than that for age-related hearing impairment, with a familial correlation of 0.15. CONCLUSION: The presence of a familial effect for tinnitus opens the door to specific studies that can determine whether this effect is due to a shared familial environment or the involvement of genetic factors. Subsequent association studies may result in the identification of the factors responsible. In addition, more emphasis should be placed on the effect of role models in the treatment of tinnitus.

Radioactive labeling and location of specific thiol groups in myosin from fast, slow and cardiac muscles.

1. Based on incorporation of radioactively labeled N-ethylmaleimide, the readily reactive thiol groups of isolated myosin (EC 3.6.1.3) from fast, slow and cardiac muscles could be classified into 3 types. All 3 myosins contain 2 thiol-1, 2 thiol-2 and a variable number of thiol-3 groups per molecule. Both thiol-1 and thiol-2 groups which are essential for functioning of the K+-stimulated ATPase, are located in the heavy chains in all 3 myosin types. 2. The variation in the incorporation pattern of N-ethylmaleimide over the 3 thiol group classes under steady-state conditions of Mg(2+) - ATP hydrolysis allowed different conformations of some reaction intermediates to be characterized. In all 3 types of myosin the hydrolytic cycle of Mg(2+) - ATP was found to be controlled by the same step at 25 degrees C. In all three cases, this rate-limiting step is changed in the same way by lowereing temperature. 3. Using the chemically determined molecular weights for myosin light chains, their stoichiometry was found on the basis of sodium dodecyl sulfate electrophoresis to be 1.2 : 2.1 : 0.8 for light chain-1: light chain-2:light chain-3 per molecule of fast myosin, 2.0 : 1.9 for light chain-1:light chain-2 per molecule of slow myosin and 1.9 : 1.9 for light chain-1:light chain-2 per molecule of cardiac myosin. This qualitative difference in light subunit composition between the fast and the two types of slow myosin is not reflected in the small variations of the characteristics exhibited by the isolated myosins, but rather seems to be connected with their respective myofibrillar ATPase activities.

Refinement of the DFNA4 locus to a 1.44 Mb region in 19q13.33.

Many forms of autosomal dominant non-syndromic hearing impairment are known. While the underlying gene defects and causative mutations have been discovered for some forms, the gene responsible for DFNA4 has remained elusive to date. Examination of a German four-generation kindred led to the identification of a 1.44 Mb map segment in contig NT_011109 as being the most likely DFNA4 candidate region in 19q13.33. The recombination breakpoints in this family and the intervals of two previously reported DFNA4 families allowed us to delineate a minimum consensus region between the markers D19S879 and D19S246. In our family, a maximum two-point LOD score of 4.5 was obtained at theta = 0 for the marker D19S867. Within the refined DFNA4 interval the public databases list more than 50 genes, from which several appear to be promising DFNA4 candidates due to similarities with animal models and with other causative genes involved in hearing disability.

Assessment of denaturing high-performance liquid chromatography (DHPLC) in screening for mutations in connexin 26 (GJB2).

Mutations in the gene GJB2 encoding connexin 26 (Cx26), a gap junction protein, have been shown to be responsible for a majority of recessive nonsyndromic hereditary hearing impairment in children. Over 60 different mutations in Cx26 have been reported. To obviate the need for direct sequencing of each specimen, a variety of screening techniques have been used to detect mutations in Cx26. However, each of these methods has significant shortcomings including expense, time consumption, and limited sensitivity. Denaturing high-performance liquid chromatography (DHPLC) has been recently introduced as a rapid and highly sensitive method of detecting sequence alterations. We have assessed the efficacy of DHPLC as a screening assay for detecting mutation in Cx26 coding region in 154 patients with hereditary hearing impairment. The GJB2 coding exon was amplified in one or two fragments, analyzed by DHPLC, and sequenced. Sequence analysis identified sequence variations in 34 patients concordant with abnormal DHPLC results. Three novel Cx26 mutations were identified: a single base pair substitution 511G>A, a 4 bp insertion 504insAACG, and a 3 bp deletion 358delAGG in three unrelated patients. In 120 patients with normal Cx26 sequence, DHPLC was normal. These results yield sensitivity and specificity of 100% for DHPLC-based detection of Cx26 mutations, and demonstrate that DHPLC is a highly sensitive and specific method of screening for sequence variations in Cx26 that is time and labor efficient. Further, our experience suggests that DHPLC screening alone followed by DNA sequencing only when DHPLC is abnormal may be adequate for identification of all sequence alterations in Cx26.

A second middle eastern kindred with autosomal recessive non-syndromic hearing loss segregates DFNB9.

A second kindred has been identified which supports the previously reported location of DFNB9. Linkage has been established to markers closely linked to DFNB9 which is located on 2p22-p23. The hearing impaired individuals in this highly consanguineous kindred from Eastern Turkey have prelingual profound hearing loss which affects all frequencies. A genetic map of the 2p22-p23 region where DFNB9 resides was generated using marker genotypes available from the CEPH database. All markers were placed on this genetic map using a likelihood ratio criterion of 1000:1. This map suggests that the region for DFNB9 is less than 1.08 cM, 95% confidence interval (0-2.59 cM).