Distortion-product emissions and auditory sensitivity in human ears with normal hearing and cochlear hearing loss.

Distortion product emissions (DPEs) at 2f1-f2 frequencies were measured in 53 human ears; 21 of them exhibited cochlear hearing loss. DPEs were obtained as a function of stimulus level (DPE growth curves) at seven frequency regions between 707 Hz and 5656 Hz. Several distinctly different shapes or patterns of DPE growth curves were observed. These included single-segment monotonic growth curves with and without saturation at moderate and high stimulus levels, diphasic growth curves with nulls at moderate stimulus levels, and non-monotonic growth curves with negative slopes at high stimulus levels. Low-level, irregularly shaped segments were more frequent in normal-hearing ears, suggestive of normal low-level active nonlinearities from the outer-hair-cell subsystem. High-level, steeply sloped segments were frequent in hearing-impaired ears, suggestive of residual nonlinearities from a cochlear partition without functional outer hair cells. The stimulus level at which the DPE could just be distinguished from the noise floor, the DPE detection threshold, demonstrated moderate positive correlations (r's from 0.50 to 0.81) with auditory thresholds when all ears, both normal and impaired, were considered together. Those correlations were not strong enough to quantitatively predict auditory thresholds with any great accuracy. However, DPE thresholds were able to predict abnormal auditory sensitivity with some precision. DPE thresholds correctly predicted abnormal auditory sensitivity 79% of the time in the present study, and up to 96% of the time in previous studies. These results suggest that DPE thresholds may prove useful for hearing screening in cases where cooperation from the subject is limited or where corroboration of cochlear hearing loss is required. Different patterns of DPE growth curves suggest underlying micro-mechanical differences between ears, but the differential diagnostic value of those patterns remains to be determined.     

Exercise induced vasodepressor syncope.

Five cases of exercise induced pure vasodepressor syncope in patients without significant structural heart disease are reported. Hypotension and symptoms of syncope or pre-syncope were induced by treadmill exercise testing and in each case limited exercise performance. Evidence of inappropriate peripheral vasodilation, probably as a consequence of ventricular mechanoreceptor stimulation, was shown in all five patients. Head up tilt testing resulted in hypotension in four patients and isoprenaline infusion in the supine position resulted in hypotension in the fifth. These patients had a new condition of exercise induced neurally mediated (vasodepressor) syncope without appreciable structural cardiac abnormalities.     

Discovering genes: the use of microarrays and laser capture microdissection in pain research

The DNA microarray is a powerful, high throughput technique for assessing gene expression on a system-wide genomic scale. It has great potential in pain research for determining the network of gene regulation in different pain conditions, and also for producing detailed gene expression maps in anatomical areas that process nociceptive stimuli. However, for the potential of this high throughput technology to be realised in pain research, microarrays need to be combined with other technologies. Laser capture microdissection is capable of isolating small populations of homogenous cells, allowing distinct areas involved in nociceptive processing to be examined. In combination with sophisticated PCR-based amplification protocols this technique provides sufficient amounts of messenger RNA (mRNA) for application to microarrays. Aside from the technological issues, a difficult task in any microarray study is the analysis of the resulting enormous data set to reveal the key genes, whose regulation is central to the phenotypic changes observed. For this to be achieved, the methods of data analysis, pattern searching and feature recognition, and bioinformatics have to be properly deployed all within the context of an appropriate statistical design. These issues are especially relevant to pain research where interindividual and interpopulation variation is likely to be high, and where polymorphisms can greatly affect nociceptive sensitivity and susceptibility to pain conditions. Methods for assessing the function of new candidate genes identified in microarray screening experiments are also discussed.     

Catheter ablation by low energy DC shocks for successful management of atrial flutter.

OBJECTIVE--To assess the effects of low energy ablation of the substrate for atrial flutter. DESIGN--Initial retrospective analysis of patients undergoing low energy ablation of the atrioventricular node for refractory atrial flutter (group 1) was followed by a prospective assessment of low energy ablation in the posterio-inferior right atrium for the same condition (group 2). SETTING--Tertiary referral centre for management of cardiac arrhythmias. PATIENTS--Seven men (aged 50-67 years) with refractory atrial flutter. INTERVENTIONS--Multiple (3-10) low energy DC shocks with a cumulative energy of 100-245 J in the region of the atrioventricular node in group 1 and 12-15 low energy DC shocks (cumulative energy 110-235 J) guided by the anatomical landmarks of the triangle of Koch and applied directly to the atrial wall. MAIN OUTCOME MEASURE--Freedom from recurrence of atrial flutter. RESULTS--In group 1 despite initial complete atrioventricular block in three patients, atrioventricular conduction had resumed in all by one month. All four, however, were in sinus rhythm at follow up six to 13 months later. Two of the three patients in group 2 were free of atrial flutter at follow up three to four months after ablation. CONCLUSION--Ablation of the atrial flutter substrate with low energy DC shocks is feasible. Precise electrophysiological mapping is not necessary.     

Sexual behavior and attitudes of University students in Northern Ireland

Two surveys of a Northern Ireland student sample were conducted in 1987 and 1988. A total of 419 female and 201 male subjects completed self-administered anonymous questionnaires concerning their behavior, knowledge, and attitudes towards sex, AIDS, homosexuality, contraception, and relationships. Results indicated a relatively low level of sexual experience, and for those with experience, relatively few partners. The possible influences of gender and religiosity on sexual behavior and attitudes, in the context of Northern Ireland, are discussed. Subjects reported considerable variation in the amount of sex education, but the majority received little or none. This student sample held relatively conservative attitudes towards love, sex, and marriage and this was particularly true for females and for regular churchgoers. In addition, attitudes towards homosexuality were negative (particularly among regular churchgoers). Attitudes towards contraception were more positive than expected among Catholic subjects, and few indicated that they would refuse to use contraceptives on principle. Responses to items about AIDS were highly uniform, suggesting that much of the information made available to the public has been absorbed. However, the lack of uniformity of response to more general items about sex, relationships, and contraception may indicate that fundamental changes in sexual behavior are unlikely to be brought about by influencing a rather narrowly defined set of attitudes about AIDS.     

Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model

We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid beta-peptide (Abeta), increases plasma concentrations of Abeta and reduces Abeta burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Abeta burden. We also found that an Abeta/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Abeta monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Abeta species.     

Subpopulations of motor and sensory neurons respond differently to brain-derived neurotrophic factor depending on the presence of the skeletal muscle.

The aim of our study was to assess the ability of brain-derived neurotrophic factor (BDNF) to rescue motor and sensory neurons from programmed cell death. It is clearly demonstrated that the administration of a single injection of a putative neurotrophic factor to mouse embryos in utero on embryonic day (E) 14.5 is sufficient to significantly reduce the death of motor neurons when assessed on E18.5. However, the trophic requirements of somatic neurons have not been unequivocally determined in a mammalian species in vivo. Indeed, the unexpectedly high numbers of surviving neurons observed in neurotrophin and tyrosine kinase receptor knockout mice are probably the consequence of functional redundancy between the neurotrophins and their receptors. We studied spinal cord and facial motor nucleus neurons and proprioceptive neurons in the dorsal root ganglion and mesencephalic nucleus. The action of BDNF was assessed in wild-type fetuses to gain insight into its ability to rescue neurons from naturally occurring programmed cell death. In addition, we used Myf5(-/-):MyoD(-/-) embryos, which completely lack skeletal musculature, to assess the ability of BDNF to rescue neurons from excessively occurring programmed cell death. We found that BDNF differentially rescued neurons from naturally vs. excessively occurring cell death and that its ability to do so varied among neuronal subpopulations.