Gender-specific response to isoflurane preconditioning in focal cerebral ischemia.

Inhalation anesthetics are effective chemical preconditioning agents in experimental cerebral ischemia. However, previous work has been performed exclusively in male animals. We determined if there is a gender difference in ischemic outcome after isoflurane preconditioning (IsoPC), and if this sex-specific response is linked to differences in Akt phosphorylation or expression of neuronal inducible cell-death putative kinase (NIPK), a negative modulator of Akt activation. Young and middle-aged male and female mice were preconditioned for 4 h with air (sham PC) or 1.0% IsoPC and recovered for 24 h. Cortices were subdissected from preconditioned young male and female mice for measurement of Akt phosphorylation (Western blot) and NIPK mRNA (quantitative polymerase chain reaction). Additional cohorts underwent 2 h of reversible middle cerebral artery occlusion. Lastly, male and female Akt1(+/+) and Akt1(-/-) mice were studied to determine if gender differences in ischemic outcome after IsoPC is Akt1-dependent. Infarction volume was determined at 22 h reperfusion (2,3,5-triphenyltetrazolium chloride). As expected, IsoPC decreased ischemic damage as compared with sham PC in young and middle-aged male mice. In contrast, IsoPC markedly increased infarction in young female mice and had no effect in middle-aged female mice. Cortical phospho-Akt was increased by IsoPC versus sham PC only in male mice. No increase was observed in IsoPC female mice. NIPK mRNA was higher in female mice than in male mice regardless of preconditioning status. Male IsoPC neuroprotection was lost in Akt1-deficient male mice. We conclude that IsoPC is beneficial only in ischemic male brain and that sex differences in IsoPC are mediated through Akt activation and basal NIPK expression.     

Sample size considerations when groups are the appropriate unit of analysis.

This article discusses issues to be considered by nurse researchers when groups should be used as the unit of randomization. Advantages and disadvantages are presented, with statistical calculations needed to determine the effective sample size. Examples of these concepts are presented using data from the Black Cosmetologists Promoting Health Program. Different hypothetical scenarios and their impact on sample size are also presented. Given the complexity of calculating the sample size when using groups as the unit of randomization, it is advantageous for researchers to work closely with statisticians when designing and implementing studies that anticipate the use of groups as the unit of randomization.     

Food and health at work–a review. The costs and benefits of a policy approach

The workplace is an important setting for health promotion and provides an ideal opportunity for shaping healthy eating patterns in occupational groups for whom inequalities have been identified (DHSS, 1980). Workplace food/health policies provide an intermediate and pragmatic step towards achieving the dietary targets set out in the Government's white paper Health of the Nation and the most recent COMA report (DoH, 1991,1992). Food/health policies have been widely adopted in the NHS (Gibson & Kallevik, 1990) and preliminary research suggests that they are an effective means of intervention (Wallis & Poulter, 1988; Frost et al., 1991). Industry has been slower to link food and health promotion to a policy making process. Surveys imply that action on healthy eating in companies often originates in the occupational health department and is based on individualistic approaches with little energy being put into preventive activities which would originate in the canteen (Mclnerney & Cooper, 1989; Poulter, 1990). Policies provide a means of balancing the environmental and educational paradigms of health promotion. If food/health policies are to grow in the private sector then industry has to be convinced that the benefits Justify the costs. Some philanthropic employers are motivated by interests other than financial gain, but others are commercially led. There is little hard evidence to demonstrate that any type of employer-sponsored healthy eating initiative provides a favourable return for investment. It has been ‘guesstimates’ and extrapolation from other situations which have provided the justification for UK companies to allocate any resources towards addressing food/health issues. In April 1990 the National Grid Company adopted a comprehensive food/health policy. This paper draws on the experiences in developing and implementing the policy document to discuss the issues around evaluative activity in a commercial setting. Views are expressed on the feasibility of measurement and the value of the informaton collected. One aim of the future should be to research this under-examined area to establish a solid body of information. This would raise the level of debate from one which is currently based on anecdotal evidence to a sounder scientific footing and, therefore, ensure the future growth of such policies in the corporate sector.     

Reflective practice: a critique of the work of Argyris and Schön

The seminal work of Argyris and Schon on action theories, technical rationality and reflective practice is reviewed, it is argued that their work reflects important inconsistencies between their theorizing and the pedagogical interventions they implemented/recommended The implications of the results of these inconsistencies, which appear mirrored in nurse-education programmes in the United Kingdom and Australia, are discussed Tentative suggestions for the provision of a more adequate practical pedagogy are included     

Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure

The N-methyl- -aspartate (NMDA) receptor has shown to play an important role in the cognitive deficits associated with developmental lead (Pb) exposure. In this study, we examined the effects of low-level Pb exposure on NMDA receptor subunit gene expression in the developing rat brain. The pattern of NR1, NR2A, NR2B, and NR2C subunit mRNA in situ hybridization was consistent with previous studies. Brain levels of NR1 and NR2A mRNAs were lowest shortly after birth, increasing to reach peak levels by 14 or 21 days of age and subsequently decreasing at 28 days of age. NR2B mRNA levels were highest during early development and decreased as the animals aged. NR2C subunit mRNA was restricted to the cerebellum and a signal was not detectable until the second week of life. Lead exposure resulted in significant and opposite effects in NR1 and NR2A subunit mRNA expression with no changes in NR2B or NR2C subunit expression. The Pb-induced changes in NR1 and NR2A subunit mRNA were mainly present in the hippocampus. Hippocampal NR1 mRNA levels were significantly increased in the CA1 (15.3%) and CA4 (26.8%) pyramidal cells from 14-day-old Pb-exposed rats. At 21 days of age, only the NR1 mRNA at the CA4 subfield remained significantly elevated (10.3%). Lead exposure caused reductions of NR2A mRNA levels (11.9–19.3%) in the pyramidal and granule cell layers of the hippocampus at 14 and 21 days of age. NR1 mRNA levels were also significantly increased (14.0%) in the cerebellum of 28-day-old rats with no change in NR2A mRNA at any age. No significant changes in subunit mRNA levels were present in cortical or subcortical regions at any age. The Pb-induced changes in hippocampal NMDA receptor subunit mRNA expression measured in the present study may lead to modifications in receptor levels or subtypes and alter the development of defined neuronal connections which require NMDA receptor activation.     

Long-latency auditory-evoked potentials: Role of polysensory association cortex in the cat

The objective of this study has been to define the role of polysensory association cortex in the generation of "wave NA" and of "wave C," long-latency auditory-evoked potentials recorded from the vertex of conscious cats as, respectively, a marked negative potential of latency 30-48 msec followed by a broad positive wave of latency 50-75 msec. Wave C may represent the feline analogue of the longer latency human auditory-evoked potential wave P2, insofar as both waveforms are very large amplitude, long duration positivities characterized by long recovery cycles. Based on previous studies of wave C and the generators of other middle-latency evoked potentials, we hypothesized that both wave NA and wave C might reflect, at least in part, the cortical culmination of a nonlemniscal line auditory association system arising in reticulothalamic projections to intralaminar and associated ventral thalamic regions. Relays from these thalamic areas are known to project to polysensory association cortex, including pericruciate gyrus, anterolateral gyrus, and medial suprasylvian gyrus. Therefore we implemented a series of lesion experiments to characterize the role of each of these cortical areas in the production of wave NA and wave C. Our results indicate that all three polysensory association areas contribute significantly to both waves NA and C, although the largest effects followed ablation of the pericruciate area alone. Thus, the generator substrates of waves NA and C appear to involve a long-recovery cycle system which functionally incorporates activation of association cortex.     

Postnatal development of the mouse dentate gyrus in organotypic cultures of the hippocampal formation

The hippocampal formation of newborn mice was explanted and maintained in Maximow culture assemblies for up to 35 days. At the time of explantation, only the suprapyramidal limb of the dentate gyrus was cytoarchitectonically distinct, and electron microscopy of newborn hippocampus revealed no definitive synapses. Histogenesis, as indicated by the development of the infrapyramidal limb of the dentate gyrus, and synaptogenesis, as indicated by the in vitro formation of mossy fiber synapses on the dendrites of hippocampal pyramidal neurons were studied by light and electron microscopy. At 12 days and thereafter in culture, mossy fiber terminals were found in synapsis with dendritic spines probably belonging to pyramidal cells of the hippocampal zone CA4. Near dentate granule cell somata a few axosomatic and many axospinous and axodendritic synapses were found. The data indicate that granule cells of the developing dentate gyrus are capable of differentiation in vitro into a structure essentially equivalent to that developed in vivo. The granule cells may become arranged into a recognizable granule cell layer, and develop dendritic processes which receive synapses virtually identical to those found in the intact organ. The differentiation of these features proceeds in the absence of the extrinsic afferents from the septum or from the contralateral hippocampal formation.     

Policies of academic medical centers for disclosing financial conflicts of interest to potential research participants.

PURPOSE: To document the current state of institutional review board (IRB) and conflict of interest committee policies regarding disclosures of financial conflicts of interest to potential research participants, and to use this information to identify and share models for effectively achieving disclosure. METHOD: The authors identified the 123 U.S. academic medical centers that have IRBs and sought their IRB and institutional policies regarding financial conflicts of interest. In February and March 2004, using manual and key word searches, each institution's Web site was searched to identify documents containing information regarding the disclosure of financial conflicts of interest. Letters were sent to 24 institutions that had either no information or incomplete information posted on their Web sites. To assess institutions' guidelines for disclosure, the authors extracted and content coded each institution's information on disclosure. RESULTS: Relevant information was obtained from 120 (98%) academic medical centers (AMCs), of which 57 (48%) mentioned disclosing financial conflicts to potential research participants. Of these 57, 33 (58%) included verbatim language that could be used in informed consent documents. AMCs' recommendations and requirements for disclosure included details of the financial arrangement, administrative management of conflicts of interest, and encouragement of dialogue between the investigator and the potential research participant. CONCLUSIONS: Considerable variability exists concerning the specific information that should be disclosed. Most of the AMCs' policies were consistent with the goal of protection from legal liability. Significant questions remain, however, concerning the goals of disclosure and the most effective methods for achieving those goals.     

A study of the increased sensitivity of denervated and re-innervated muscle to depolarizing drugs

1. The response of re-innervated muscles to depolarizing blocking drugs was studied.

2. During the early stages of re-innervation the `new' neuromuscular junctions are more sensitive to decamethonium and suxamethonium. The recovery from the block and the repolarization of the end-plate are markedly slowed.

3. This increased sensitivity does not appear to be characteristic of all newly formed neuromuscular junctions. It was found that in new-born kittens the muscles are very insensitive to neuromuscular blocking drugs.

4. It is concluded that the increased sensitivity of re-innervated muscles to depolarizing blocking drugs and the slow repolarization are due to a persistence of changes which developed during denervation.