Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness

Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.     

Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Articulation of Asthma and Its Care Among Low-Income Emergency Care Recipients

Low-income minority patients from East St. Louis, Illinois, a depressed midwestern urban city, who had visited acute care settings with asthma symptoms, participated in a focus group. Questions were constructed around the Health Belief Model to characterize participants' experiences in receiving asthma care, their confidence in long-term asthma self-management, barriers they perceived to managing their asthma, and recommendations they would make for improving asthma care in their community. Analysis of comments suggests an appreciable understanding of asthma triggers, limited coping behaviors for asthma symptoms, very limited practice of active asthma management, perception of the health care system as frequently insensitive to their needs or their knowledge of their own care, exchange of well-articulated information regarding how to deal with the system, and an apparent lack of awareness of any potential contribution of patient education or support system.     

Albumin Adsorption and Retention on C18-Alkyl-Derivatized Polyurethane Vascular Grafts

The short-term albumin affinity and thrombo-resistance of a polyether polyurethane vascular graft have been improved. The method is based on the C18 alkylation of the polymer. Thrombus formation by a planimetric technique and albumin retention on wire-reinforced polyurethane tubes, both C18 alkylated and untreated, were measured in short-term (4-h) exposure at femoral arterial sites in the dog. 125I-Albumin was preabsorbed on tubes and then exposed to blood for successive 2-h periods. Albumin uptake on alkylated tubes prior to blood exposure and retention following 2 h of blood exposure were significantly greater than on controls. Following a fast desorption phase in blood, the remaining albumin was more slowly desorbed from alkylated than from control tubes. Reincubation with albumin and blood reexposure produced a similar tendency, suggesting blood conditioning does not reduce the albumin affinity-enhancing property of C18 alkylation in the short term. Blood-preconditioning experiments suggested endogenous albumin has a high affinity for the C18-alkylated surface. Scanning electron microscopic examination showed thrombus and platelet densities were higher on control than on alkylated surfaces. These results suggest in vivo albumin affinity is increased for C18-alkylated polyurethane, which may be linked to decreased thrombus formation on these surfaces.     

Do budget-holding physicians respond to price? the case of fundholding in the UK.

In an effort to improve the efficiency of the healthcare sector, some countries have experimented with various forms of 'internal market' in public healthcare provision. In some models, policymakers have assumed that actors will behave, as in a retail market, by responding to price in the course of seeking the best 'value for money' from healthcare providers. In the study reported here we examined the responsiveness of general practitioners to price during the British experiment in general practice (GP) fundholding. The study analysed routine data on 29 423 referrals for elective care made by 129 practices in one city to two competing providers of secondary care. Indices of price responsiveness were calculated for each practice from their manifest referral behaviour. These were then used to compare fundholding and non-fundholding practices. The results showed no difference between these groups in their propensity to respond to published procedure prices, even when potential savings were very large. Our findings are consistent with the reported views of fundholding GPs that price was a secondary consideration in their referral behaviour, and provides further evidence that healthcare markets cannot be understood in simplistic terms.     

HERPES SIMPLEX VIRUS ENCEPHALITIS: PROBLEMS IN DIAGNOSIS

Six children aged 13 days to nine years with herpes simplex encephalitis (HSE) are presented. Institution of appropriate antiviral treatment was later than six days in three cases; original diagnosis in these cases were post-traumatic epilepsy, bacterial meningitis and febrile convulsion. Initially pyrexia was absent in two cases and cranial CT was normal in two cases. Encephalitic changes were observed on the EEGs of five children. Diagnosis was confirmed by paired serological titres, brain biopsy, vesicle culture and CSF titres. The outcome for all six children was poor. HSE should always be considered in children presenting with focal seizures, even when apyrexial and with normal CT findings. In such situations, saving CSF for antibody titres or antigen identification should be routine practice. Treatment with acyclovir is justified before precise virological diagnosis has been established.     

Examining the range of normal intraindividual variability in neuropsychological test performance.

Neuropsychologists often diagnose cerebral dysfunction based, in part, on marked variation in an individual's cognitive test performance. However, little is known about what constitutes the normal range of intraindividual variation. In this study, after excluding 54 individuals with significant health problems, we derived 32 z-transformed scores from 15 tests administered to 197 adult participants in a study of normal aging. The difference between each person's highest and lowest scores was computed to assess his or her maximum discrepancy (MD). The resulting MD values ranged from 1.6 to 6.1 meaning that the smallest MD shown by any person was 1.6 standard deviations (SDs) and the largest MD shown by any person was 6.1 SDs. Sixty-six percent of participants produced MD values that exceeded 3 SDs. Eliminating each person's highest and lowest test scores decreased their MDs, but 27% of the participants still produced MD values exceeding 3. Although MD values appeared to increase with age, adjusting test scores for age, which is standard in clinical practice, did not correct for this. These data reveal that marked intraindividual variability is very common in normal adults, and underscore the need to base diagnostic inferences on clinically recognizable patterns rather than psychometric variability alone.     

Beauty and the eye of the beholder: social consequences and personal adjustments for facial patients

Patients' pre- and postoperative self-reports were compared with reports of non-medical observers to investigate whether improved self-esteem is a direct result of increased social acceptance in maxillo- and craniofacial patients. Twenty-two children and adolescents undergoing reconstructive surgery for a variety of facial deformities were asked to rate their physical appearance on the Hay's Scale and fill out the Piers-Harris Self-Concept Scale. Their ratings were compared with scores given by a panel of lay volunteers on random presentation of pre- and postoperative photographs of the same patients. Patients rated their appearance as noticeably improved after surgery, their self-esteem rose significantly and they reported more social adeptness and acceptance at home and school. Raters observed only relatively subtle changes. Apparently, quality of life improved for the postsurgical facial patient because of increased self-esteem and confidence, which free him to overcome social barriers.