Objective: A national survey of early hearing detection services was undertaken to describe the demographics, protocols and performance of early hearing detection, referral, follow-up and data management practices in the private health care sector of South Africa.Methods: All private hospitals with obstetric units (n=166) in South Africa were surveyed telephonically. This data was incorporated with data collected from self-administered questionnaires subsequently distributed nationally to audiology private practices providing hearing screening at the respective hospitals reporting hearing screening services (n=87). Data was analyzed descriptively to yield national percentages and frequency distributions and possible statistical associations between variables were explored.Results: Newborn hearing screening was available in 53% of private health care obstetric units in South Africa of which only 14% provided universal screening. Most (81%) of the healthy baby screening programs used only otoacoustic emission screening. Auditory brainstem response screening was employed by 24% of neonatal intensive care unit screening programs with only 16% repeating auditory brainstem response screening during the follow-up screen. Consequently 84% of neonatal intensive care unit hearing screening programs will not identify auditory neuropathy. A referral rate of less than 5% for diagnostic assessments was reported by 80% of universal programs. Follow-up return rates were reported to exceed 70% by only 28% of programs. Using multiple methods of reminding parents did not significantly increase reported follow-up return rates. Data management was mainly paper based with only 10% of programs using an electronic database primarily to manage screening data. Conclusions:A shortage of programs and suboptimal and variable protocols for early hearing detection, follow-up and data management in existing programs mean the majority of babies with hearing loss in the South African private health care sector will not be identified early. Newborn hearing screening must be integrated with hospital-based birthing services, ideally with centralized data management and quality control.
1 The structure-activity relationship for hypoglycaemic sulphonylureas and analogues was examined. Binding a nities were compared using membranes from HIT-T15 cells (b-cell line) and from COS-7 cells transiently expressing sulphonylurea receptor subtypes (SUR1, SUR2A and SUR2B). Inhibition of adenosine-triphosphate-sensitive K + channels (K ATP -channels) was measured in mouse pancreatic b-cells. 2 The tested compounds displayed similar binding a nities for SUR2A and SUR2B. 3 Meglitinide (benzoic acid derivative) bound to SUR1 and the SUR2 isoforms with similar a nities. Replacement of the carboxyl group of meglitinide by a methyl group signi®cantly decreased the binding a nities for SUR1 and the SUR2 isoforms (44 fold) and the potency to inhibit K ATP -channel activity of b-cells (24 fold). Replacement of the carboxyl group of meglitinide by a sulphonylurea group signi®cantly increased the a nities for SUR1 (5 fold) and the SUR2 isoforms (13 ± 16 fold). 4 Glibenclamide bound to the SUR2 isoforms with 300 ± 500 fold lower a nity than to SUR1. Exchanging the cyclohexyl ring of glibenclamide by a methyl group or removal of the lipophilic side chain of glibenclamide (5-chloro-2-methoxy-benzamidoethyl chain) markedly reduced but did not abolish the selectivity for SUR1. 5 In conclusion, interaction of sulphonylureas and acidic analogues with SUR1, SUR2A and SUR2B is favoured by the anionic group of these drugs. Hypoglycaemic sulphonylureas (e.g. glibenclamide) owe selectivity for SUR1 to lipophilic substitution on their urea group. Sulphonylureas without lipophilic substitution on the urea group could represent lead compounds for the development of SUR2-selective drugs.
BackgroundFalls frequency increases with age and particularly in neurogeriatric cohorts. The interplay between eye movements and locomotion may contribute substantially to the occurrence of falls, but is hardly investigated. This paper provides an overview of current approaches to simultaneously measure eye and body movements, particularly for analyzing the association of vestibulo-ocular reflex (VOR) suppression, postural deficits and falls in neurogeriatric risk cohorts. Moreover, VOR suppression is measured during head-fixed target presentation and during gaze shifting while postural control is challenged. Using these approaches, we aim at identifying quantitative parameters of eye-head-coordination during postural balance and gait, as indicators of fall risk.Methods/DesignPatients with Progressive Supranuclear Palsy (PSP) or Parkinson’s disease (PD), age- and sex-matched healthy older adults, and a cohort of young healthy adults will be recruited. Baseline assessment will include a detailed clinical assessment, covering medical history, neurological examination, disease specific clinical rating scales, falls-related self-efficacy, activities of daily living, neuro-psychological screening, assessment of mobility function and a questionnaire for retrospective falls. Moreover, participants will simultaneously perform eye and head movements (fixating a head-fixed target vs. shifting gaze to light emitting diodes in order to quantify vestibulo-ocular reflex suppression ability) under different conditions (sitting, standing, or walking). An eye/head tracker synchronized with a 3-D motion analysis system will be used to quantify parameters related to eye-head-coordination, postural balance, and gait. Established outcome parameters related to VOR suppression ability (e.g., gain, saccadic reaction time, frequency of saccades) and motor related fall risk (e.g., step-time variability, postural sway) will be calculated. Falls will be assessed prospectively over 12 months via protocols and monthly telephone interviews.DiscussionThis study protocol describes an experimental setup allowing the analysis of simultaneously assessed eye, head and body movements. Results will improve our understanding of the influence of the interplay between eye, head and body movements on falls in geriatric high-risk cohorts.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-015-0447-5) contains supplementary material, which is available to authorized users.
1 The structure activity relationships for the insulin secretagogues N-benzoyl-D-phenylalanine (NBDP) and related compounds were examined at the sulphonylurea receptor level by use of cultured HIT-T15 and mouse pancreatic b-cells. The a nities of these compounds for the sulphonylurea receptor were compared with their potencies for K ATP -channel inhibition. In addition, the e ects of cytosolic nucleotides on K ATP -channel inhibition by NBDP were investigated. 2 NBDP displayed a dissociation constant for binding to the sulphonylurea receptor (K D value) of 11 mM and half-maximally e ective concentrations of K ATP -channel inhibition (EC 50 values) between 2 and 4 mM (in the absence of cytosolic nucleotides or presence of 0.1 mM GDP or 1 mM ADP). 3 In the absence of cytosolic nucleotides or presence of GDP (0.1 mM) maximally e ective concentrations of NBDP (0.1 ± 1 mM) reduced K ATP -channel activity to 47% and 44% of control, respectively. In the presence of ADP (1 mM), K ATP -channel activity was completely suppressed by 0.1 mM NBDP. 4 The L-isomer of N-benzoyl-phenylalanine displayed a 20 fold lower a nity and an 80 fold lower potency than the D-isomer. 5 Introduction of a p-nitro substituent in the D-phenylalanine moiety of NBDP did not decrease lipophilicity but lowered a nity and potency by more than 30 fold. 6 Introduction of a p-amino substituent in the D-phenylalanine moiety of NBDP (N-benzoyl-p-amino-D-phenylalanine, NBADP) reduced lipophilicity and lowered a nity and potency by about 10 fold. This loss of a nity and potency was compensated for by formation of the phenylpropionic acid derivative of NBADP. A similar di erence in a nity was observed for the sulphonylurea carbutamide and its phenylpropionic acid derivative. 7 Replacing the benzene ring in the D-phenylalanine moiety of NBDP by a cyclohexyl ring increased lipophilicity, and the K D and EC 50 values were slightly lower than for NBDP. Exchange of both benzene rings in NBDP by cyclohexyl rings further increased lipophilicity without altering a nity and potency. 8 This study shows that N-acylphenylalanines interact with the sulphonylurea receptor of pancreatic bcells in a stereospeci®c manner. Their potency depends on lipophilic but not aromatic properties of their benzene rings. As observed for sulphonylureas, interaction of N-acylphenylalanines with the sulphonylurea receptor does not induce complete inhibition of K ATP -channel activity in the absence of inhibitory cytosolic nucleotides.
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