Synaptic potentials and effects of amino acid antagonists in the auditory cortex

Neurons of in vitro guinea pig and rat auditory cortex receive a complex synaptic pattern of afferent information. As many as four synaptic responses to a single-stimulus pulse to the gray or white matter can occur; an early-EPSP followed, sequentially, by an early-IPSP, late-EPSP, and late-IPSP. Paired pulse stimulation and pharmacological studies show that the early-IPSP can modify information transmission that occurs by way of the early-EPSP. Each of these four synaptic responses differed in estimated reversal potential, and each was differentially sensitive to antagonism by pharmacological agents. DNQX (6,7-dinitroquinoxaline-2,3-dione), a quisqualate/kainate receptor antagonist, blocked the early-EPSP, and the late-EPSP was blocked by the NMDA receptor antagonist APV (D-2-amino-5-phosphonovalerate). The early-IPSP was blocked by the GABA-a receptor antagonist bicuculline, and the late-IPSP by the GABA-b receptor antagonists 2-OH saclofen or phaclofen. Presentation of stimulus trains, even at relatively low intensities, could produce a long-lasting APV-sensitive membrane depolarization. Also discussed is the possible role of these synaptic potentials in auditory cortical function and plasticity.     

Impact of Increasing Margin Around the Lumpectomy Cavity to Define the Planning Target Volume for 3D Conformal External Beam Accelerated Partial Breast Irradiation

The purpose of this study was to evaluate the dose to normal tissues as a function of increasing margins around the lumpectomy cavity in accelerated partial breast irradiation (APBI) using 3D-conformal radiotherapy (3DCRT). Eight patients with Stage 0-I breast cancer underwent treatment planning for 3DCRT APBI. The clinical target volume (CTV) was defined as a 15-mm expansion around the cavity limited by the chest wall and skin. Three planning target volumes (PTV1, PTV2, PTV3) were generated for each patient using a 0, 5-, and 10-mm expansion around the CTV, for a total margin of 15, 20, and 25 mm. Three treatment plans were generated for every patient using the 3 PTVs, and dose-volume analysis was performed for each plan. For each 5-mm increase in margin, the mean PTV:total breast volume ratio increased 10% and the relative increase in the mean ipsilateral breast dose was 15%. The mean volume of ipsilateral breast tissue receiving 75%, 50%, and 25% of the prescribed dose increased 6% to 7% for every 5 mm increase in PTV margin. Compared to lesions located in the upper outer quadrant, plans for medially located tumors revealed higher mean ipsilateral breast doses and 20% to 22% more ipsilateral breast tissue encompassed by the 25% IDL. The use of 3DCRT for APBI delivers higher doses to normal breast tissue as the PTV increases around the lumpectomy cavity. Efforts should be made to minimize the overall PTV when this technique is used. Ongoing studies will be necessary to determine the clinical relevance of these findings.     

A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone.

AIM: To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose. RESULTS: Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group. CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.     

The application of crime science to the prevention of elder abuse

The abuse of older people is a significant problem, with estimates intimating that there may be over 340,000 cases per year in the United Kingdom. Despite improvements in screening and assessment to identify and treat those who are abused or at risk of abuse, the healthcare community remains preoccupied with prevalence rather than prevention. In light of the paucity of health-related research evidence to support the effectiveness of preventative measures, the application of crime prevention theory and knowledge is appropriate. Routine activity theory and situational crime prevention literature acknowledges the vulnerability of older people to abuse and the potential of any person employed as a carer to be an abuser. Preventative measures are focused on techniques that make abuse more difficult and more risky for the perpetrator and, therefore, less 'rewarding'. The regulation of healthcare support workers and increased workplace surveillance are examples of the 25 techniques of situational prevention that could be applied in a healthcare setting.     

Wavefront aberration and its relationship to the accommodative stimulus-response function in myopic subjects.

BACKGROUND: Autorefractors are increasingly used in myopia research because they are convenient tools to investigate aspects of the accommodation response. The degree to which the autorefractor measures are affected by ocular aberrations has been highlighted by studies that have shown changes in aberration levels through different parts of the pupil and with accommodation. We have compared accommodative accuracy as measured with a Shin-Nippon SRW 5000 autorefractor with wavefront error as measured with a Hartmann-Shack wavefront sensor to investigate how factors such as accommodation demand, ocular aberrations, and pupil size can influence autorefractor measures. METHODS: Accommodation stimulus-response curves were determined (using negative lenses) for 30 young healthy subjects (20 myopic [-0.75 to -6.00 D] and 10 emmetropic). Accommodation levels ranged from 0 to 4 D in 1 D steps. Wavefront aberrations were also determined for the same accommodation levels using a Hartmann-Shack wavefront sensor for both the subjects' natural pupil sizes and for a 2.9-mm pupil. RESULTS: For all subjects, there was a consistent increase in negative spherical aberration with increases in accommodative stimulus. However, there was no consistent change in paraxial spherocylindrical refractive correction with accommodation stimulus. For the emmetropic subjects, accommodation error as measured with the autorefractor was statistically similar to the total spherocylindrical correction for the eye as estimated by the Hartmann-Shack wavefront sensor, but only for a 2.9-mm pupil (the pupil size utilized by the autorefractor). For the myopic subjects, accommodation error as measured with the autorefractor was statistically similar to the higher-order aberrations, but only when measured for a natural pupil size. CONCLUSIONS: The relationship between the accommodation accuracy as measured with the autorefractor and the total wavefront aberration as measured with a Hartmann-Shack wavefront sensor is largely influenced by the higher-order (fourth and above) aberration levels. For the emmetropic subjects, the errors measured by the two methods agree when adjusted to measure at similar pupil sizes. For the myopic subjects with similar pupil sizes, however, the Hartmann-Shack wavefront sensor underestimates the accommodation error at higher accommodation levels (2 to 4 D) compared with the autorefractor.     

A brief self-rating scale for PTSD after road vehicle accident

The Accident Fear Questionnaire (AFQ) is a new self-rated scale for PTSD and “accident phobia” (subsyndromal PTSD) after road vehicle accident (RVA). AFQ data from 54 RVA survivors were compared with two clinician-rated and three self-report measures of psychopathology. Diagnoses were based on the DSM-III-R structured clinical interview for PTSD and on DSM-III-R criteria for specific phobia. Diagnostic groups were similar in regards to demographic variables, duration of illness, measures of pain, self-rated physical impairment, and duration of illness. The AFQ had good internal consistency with a Crohnbach's alpha of 0.89 and yielded the largest group differences between PTSD (n = 12), “accident phobia” (n = 14), and neither diagnosis (n = 28). Subjects with PTSD tended to score highest on all self-report measures of psychopathology, followed by “accident phobics”, followed by subjects with neither diagnosis. On the AFQ, this order of severity was preserved after subjects with major depression had been removed from the analysis. Lacking effects from depression and from pain suggest that the AFQ is a specific measure of RVA-related phobic avoidance.     

Functional MR activation correlated with intraoperative cortical mapping.

PURPOSETo evaluate the spatial specificity of functional MR imaging by comparing it with intraoperative electrocortical mapping.METHODSFunctional MR imaging was performed in 28 patients before awake craniotomy and intraoperative electrocortical mapping. Activation was mapped for finger movement, lip movement, tongue movement, word generation, and counting paradigms. During surgery, finger movement, lip movement, tongue movement, counting, and/or speaking were mapped. The functional images and the photographic recordings of the brain functions mapped during surgery were converted to bit maps and coregistered by a computer program. The distance between the intraoperatively mapped function site and the MR activation site for a comparable function was measured.RESULTSForty-six functions were recorded on MR images and intraoperative maps. In 100% of correlations, the intraoperative site and the MR activation site were within 20 mm; in 87% of correlations they were within 10 mm. For each paradigm, 67% or more of the intraoperative stimulation maps correlated within 10 mm of the MR activation site.CONCLUSIONSFor the tasks used in this study, the activation site on functional MR images correlated well with the site at which intraoperative stimulation identified function.     

Supercritical fluid extraction in the determination of tobacco-specific N-nitrosamines in smokeless tobacco.

A new approach to the analysis of the carcinogenic, tobacco-specific N-nitrosamines (TSNA) in moist snuff tobacco is based on the extraction of tobacco with methanol-modified supercritical carbon dioxide. Extracted TSNA are trapped across a glass cartridge filled with Tenax GR, from which they are subsequently released by thermal desorption and analyzed by capillary gas chromatography with a thermal energy analyzer. The analytical recoveries for the major TSNA range from 83 to 98%; the detection limits are below 2 ng/g. The methodology is fast, reproducible, highly selective, and sensitive. The supercritical fluid extraction (SFE) releases up to 7 times more of the highly carcinogenic 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) from tobacco than has been determined after conventional solvent extraction. Studies have confirmed that this is not an artifact. In contrast, the cyclic N-nitrosamines, N'-nitrosonornicotine, N'-nitrosoanabasine, and N'-nitrosoanatabine, showed no significant quantitative differences whether determined by the SFE method or the conventional solvent extraction method.