Affinity labeling of mu opioid receptors by sulfhydryl alkylating derivatives of morphine and morphinone.

After reduction of a disulfide bond at or near the mu opioid binding site in rat brain membranes, incubating membranes with 14 beta-bromoacetamido derivatives of either morphine, dihydromorphine, morphinone, or dihydromorphinone resulted in the irreversible inhibition of mu opioid binding to rat brain membranes. Without the addition of the disulfide bond-reducing reagent dithiothreitol, these affinity ligands bound reversibly to opioid binding sites. Binding to either delta or kappa opioid binding sites was not altered by alkylation of the membranes with the affinity ligands. The percentage of irreversible inhibition of mu opioid binding was dependent on the time and temperature of the incubation of membranes with the affinity ligands and on the concentrations of dithiothreitol and the affinity ligands. Incubating membranes with morphine afforded almost complete protection from alkylation of the mu opioid binding site. Naloxone and the l-isomer levorphanol also protected the site from alkylation, whereas the d-isomer dextrorphan and the kappa-selective opioid U50,488H did not protect the site. The mu-selective peptide [D-Ala2, (Me)Phe4,Gly(ol)5]enkephalin was the peptide that afforded the greatest protection. These studies have shown that, after the reduction of a disulfide bond at or near the mu opioid binding site, this sulfhydryl group can be specifically alkylated, resulting in the affinity labeling of the mu opioid binding site.     

New aspects of airway mechanics in pre-term infants.

High-frequency respiratory impedance data measured noninvasively by the high-speed interrupter technique (HIT), particularly the first antiresonance frequency (f(ar,1)), is related to airway wall mechanics. The aim of this study was to evaluate the feasibility and repeatability of HIT in unsedated pre-term infants, and to compare values of f(ar,1) from 18 pre-term (post-conceptional age 32-37 weeks, weight 1,730-2,910 g) and 18 full-term infants (42-47 weeks, 3,920-5,340 g). Among the pre-term infants, there was good short-term repeatability of f(ar,1) within a single sleep epoch (mean (sd) coefficient of variance: 8 (1.7)%), but 95% limits of agreement for repeated measures of f(ar,1) after 3-8 h were relatively wide (-41 Hz; 37 Hz). f(ar,1) was significantly lower in pre-term infants (199 versus 257 Hz), indicating that wave propagation characteristics in pre-term airways are different from those of full-term infants. The present authors suggest that this is consistent with developmental differences in airway wall structure and compliance, including the influence of the surrounding tissue. Since flow limitation is determined by wave propagation velocity and airway cross-sectional area, it was hypothesised that the physical ability of the airways to carry large flows is fundamentally different in pre-term than in full-term infants.     

Chemosensory event-related potentials in relation to side of stimulation, age, sex, and stimulus concentration.

OBJECTIVE: For chemosensory event-related potentials (ERP) significant effects of age and sex have been demonstrated. The aim of the present study was to assess the effects of stimulus concentration, side of stimulation, and sex on the topographical distribution of chemosensory ERP in a large group of subjects stratified for different age groups. In addition, psychophysical measures of both olfactory and trigeminal function should be assessed in greater detail compared to previous work. METHODS: A total of 95 healthy subjects participated in the study. Olfactory functions were tested using the 'Sniffin' Sticks' comprising tests of odor identification, odor discrimination, and odor threshold. Trigeminal sensitivity was assessed on a psychophysical level using a lateralization paradigm. ERP to the olfactory stimulant H2S and the trigeminal irritant CO2 were recorded; stimuli were presented in different concentrations to the left and right nostril. RESULTS: Olfactory thresholds exhibited an age-related increase while the outcome of psychophysical trigeminal tests was not significantly affected by age. In contrast, there was no significant main effect of the factor 'sex' for olfactory tests, while women scored higher than men in the trigeminal task. ERP to olfactory and trigeminal stimuli exhibited a relationship to stimulus concentration, age, and sex with youngest women showing largest amplitudes and shortest latencies. There was no significant main effect of left- or right-sided stimulation on ERP. Measures of olfactory function were found to correlate with parameters of olfactory ERP even when controlling for the subject's age. In addition, correlations between scores in the lateralization task and parameters of the trigeminal ERP were found. CONCLUSIONS: Based on electrophysiological data obtained in a large sample size the present results established an age-related loss of olfactory and trigeminal function, which appears to be almost linear. Further, the present results emphasize that responses to chemosensory stimuli are related to sex, while the side of stimulation does not play a major role in the presently used paradigm. Finally, these data establish the lateralization paradigm as a psychophysical tool to investigate intranasal trigeminal function. SIGNIFICANCE: The present results obtained in a representative group of healthy subjects establishes a comprehensive set of data, which will serve as reference for future work in this area of research.     

A comparison of the stressors experienced by parents of intubated and non-intubated children

When children are ill enough to require admission to paediatric intensive care, parents may become distressed about their child's medical condition and this distress may be compounded by the unfamiliar nature of the highly technological environment Parents of children who are sick enough to warrant intubation are particularly likely to be exposed to a frightening array of technological equipment Seventy-one parents of intubated and non-intubated children completed the Parental Stressor Scale Paediatnc Intensive Care Unit (PSS PICU) Overall the findings suggest that parents were most distressed (a) by the painful procedures to which their children were subjected, (b) by the sights and sounds of the intensive care unit and (c) by their children's reactions to intensive care The behaviour of staff towards parents and the way that staff communicated with them caused the least distress When the levels of stress reported by parents of intubated children were compared with those reported by parents of non-intubated children, different patterns of stress were found Painful procedures were a source of greater stress to parents of intubated children whereas the behaviour of staff and the children's reactions to the intensive care experience caused greater stress to the parents of the non-intubated children In general the findings suggest that the needs of parents of non-intubated children are being overlooked, with staff focusing more of their attention on the parents of intubated children     

A critical analysis of attenuation effects of different types of ear protective devices

The present study was undertaken to evaluate the noise attenuation characteristics of different types of Ear protective Devices which are commonly used. 20 healthy normal subjects’ open and closed hearing thresholds (with the usage of ear protective device) were recorded in an anechoic chamber and the attenuation charactaristics at 8 discrete frequencies were analysed and compared. Though the attenuation given by different types of ear protective devices are variable and not the ideal, still the present generation of devices have shown satisfactory attenuation characteristics, It is important that proper selection, fitment and usage of these devices should he carefully thought of prior to its usage.     

Pathologic features of cytomegalovirus retinopathy after treatment with the antiviral agent ganciclovir

Ganciclovir is a new antiviral compound (also called BW B759U, DHPG, BIOLF-62, and 2'NDG) that has been used for the treatment of cytomegalovirus (CMV) retinopathy in immunocompromised patients (bone marrow recipients or acquired immune deficiency syndrome [AIDS] victims). The authors studied the eyes of three AIDS patients with CMV retinopathy who died while receiving ganciclovir chemotherapy. Gross, microscopic, and ultrastructural studies of these cases showed varying degrees of retinal scarring and active CMV lesions at the margins of the scars. CMV antigens were localized in cells at all layers of retina at the border of the lesions and in isolated cells in a perivascular location within histologically normal appearing retina. These areas probably represent sites of recrudescence when the drug is discontinued. In situ hybridization using a cloned complementary DNA (cDNA) probe of human CMV corroborated the immunocytologic localization of the virus. Ultrastructural studies showed megalic syncytial cells containing mostly capsids exclusively in the cell nucleus. The cytoplasmic electron-dense membrane-bound bodies that have characterized untreated cases of CMV retinopathy were absent in the treated cases. An attempt to isolate CMV in tissue culture from the vitreous and retina of one of the cases yielded a negative result. Our results indicate that ganciclovir does not effectively eliminate CMV from the retina nor does it suppress expression of all viral genes. Ganciclovir appears to function by limiting viral DNA synthesis and subsequent packaging of viral DNA into infectious units, thereby acting as a virostatic chemotherapeutic agent.     

Invasive ventilation in the emergency department: Part 2: Implications for patient safety

The use of mechanical ventilation in the Emergency Department requires adequate resources in order to maintain patient safety and avoid potential risks. Moreover, developments in technology require increased knowledge of mechanical ventilation techniques to address the complexity of decision-making involved. Organisational issues and system factors have the potential to negatively impact on the ability of the emergency service to provide optimum care to patients receiving mechanical ventilation. These issues include staffing and skill-mix, demand on emergency services, role-delineation, scope of practice, and current mechanisms for monitoring of quality and safety. Furthermore, in response to advances in ventilator technology, current education programs for both nursing and medical staff require review to ensure that they provide comprehensive information about the types of ventilation techniques now available and the relative risks and benefits associated with their application.This article is the second in a two-part series and explores the educational and organisational factors that impact upon safety and quality of care delivered to patients receiving mechanical ventilation in the emergency department. Recommendations for future policy development, curriculum review and reporting mechanisms to support further research in the application of mechanical ventilation in the emergency department are made.     

Differentiation of radioligand delivery and binding in the brain: validation of a two-compartment model for [11C]flumazenil

We recently developed a two-compartment, two-parameter tracer kinetic model to estimate the in vivo ligand transport rate (K1) and distribution volume (DV) for the benzodiazepine antagonist [11C]flumazenil (FMZ) as measured by positron emission tomography (PET). The aim of the present study was to validate that this simplified model provides a stable measure of regional benzodiazepine receptor availability even when ligand delivery is altered. Six young normal volunteers underwent two PET studies subsequent to intravenous injections of [11C]FMZ. Each FMZ study was immediately preceded by measurements of CBF following injection of [15O]water. One set of scans (water/FMZ) was acquired under resting conditions and the other set during audiovisual stimulation. Six additional volunteers underwent two FMZ studies under identical resting conditions. Parametric images were analyzed and a comparison of test-retest studies in the stimulation group revealed a significant increase of CBF and K1 of FMZ in the occipital cortex evoked by visual activation, whereas no regional changes were noted for the DV of FMZ. No significant changes were noted for either K1 or DV of FMZ when comparing studies in the rest-rest setting. The results indicate that the use of a simple two-compartment model for the tracer kinetic analysis of [11C]FMZ makes it possible to separate high-affinity binding from altered radio-ligand delivery to the human brain.