The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery.

We investigated the influence of either propofol or desflurane on the incidence of postoperative cognitive dysfunction in a randomised trial of 180 patients undergoing coronary artery bypass surgery. The primary outcome was incidence of postoperative cognitive dysfunction at 3 months, defined as ≥1 SD deterioration in two or more of 12 neurocognitive tests. Secondary outcomes included early postoperative cognitive dysfunction (between days three and seven), delirium on day one, morbidity and length of hospital stay. Early postoperative cognitive dysfunction was significantly higher with propofol compared with desflurane (56/84 (67.5%) vs 41/83 (49.4%), respectively, p=0.018), but this effect was not seen at 3 months (10/87 (11.2%) vs 9/90 (10.0%), respectively. There was no difference in delirium (7/89 (7.9%) vs 12/91 (13.2%), respectively, length of hospital stay (median (IQR [range]) 7 (6-9 [4-15]) vs 6 (5-7 [5-16) days, respectively or other morbidities. Desflurane was associated with reduced early cognitive dysfunction.

The impact of a breast cancer diagnosis on religious/spiritual beliefs and practices in the UK.

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women (n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made.

Religious coping strategies in patients diagnosed with breast cancer in the UK.

OBJECTIVES: The use of religious/spiritual coping strategies may be particularly prevalent when dealing with the stress of a cancer diagnosis. There has, however, been very little research conducted on this topic outside the USA. Existing measures of coping largely ignore the complexity of religious/spiritual coping and its potential to be adaptive as well as maladaptive. The aim of this study was to examine the prevalence of various religious coping strategies in a UK cancer sample. METHOD: A longitudinal design assessed religious coping strategies in patients newly diagnosed with breast cancer at the time of surgery and at 3 and 12 months post surgery. We recruited 202 patients of which, at 12 months, 160 remained. A non-religious coping measure was included for comparison. RESULTS: The use of religious coping strategies was overall common; up to 73% of patients used positive religious coping to some degree at surgery and up to 53% experienced various religious/spiritual struggles. The use of some religious coping strategies showed differing patterns of change across time while others remained stable. CONCLUSION: Using religious/spiritual resources in the coping process during the early stages of breast cancer appears common in the UK. Patients may benefit from having their spiritual needs addressed as experiencing some form of religious/spiritual struggle may serve as a barrier to illness adjustment. Health-care professionals should also be aware that some religious coping strategies may be more prevalent at different times during the first year of illness.

Evaluation of an alternative S100b assay for use in cardiac surgery: relationship with microemboli and neuropsychological outcome.

INTRODUCTION: The aim of the study was to investigate the relationship between S100b release, neuropsychological outcome and cerebral microemboli. Peri-operative assay of the astroglial cell protein S100b has been used as a marker of cerebral damage after cardiac surgery but potential assay cross-reactivity has limited its specificity. The present study uses an alternative enzyme-linked immunoabsorbant assay (ELISA) for serum S100b that has documented sensitivity and specificity data in patients undergoing coronary artery bypass grafting (CABG). METHODS: Fifty-five consecutive patients undergoing routine CABG surgery received serial venous S100b sampling at five time points: i) Pre-operative, ii) At the end of cardiopulmonary bypass (CPB), iii) 6 hrs, iv) 24 hrs and v) 48 hrs post skin closure. A previously described sandwich ELISA with monoclonal anti- S100b was used. This assay has a lower limit of detection of 0.04 microg/L and < 0.006% reactivity with S100a at a concentration of 100 microg/L S100a. Cerebral microemboli during surgery were recorded by transcranial Doppler monitor over the right middle cerebral artery. Evidence of cerebral impairment was obtained by comparing patients' performance in a neuropsychological battery of 9 tests administered 6-8 weeks post-operatively with their pre-operative scores. RESULTS: There was a significant increase in S100b only at the end of bypass (mean 0.30 microg/L, SD +/- 0.33 and range .00 to 1.57). S100b levels at the end of bypass did not correlate with neuropsychological outcome or microemboli counts. CONCLUSIONS: The low levels of S100b detected using the present assay, despite its high sensitivity and despite the routine use of cardiotomy suction, suggest that the assay may have higher specificity for cerebral S100b than previously used assays. There was no evidence that this assay is related to neuropsychological change or cerebral microemboli in cardiac surgery.

Neuroprotection during cardiac surgery: strategies to reduce cognitive decline.

Although the population receiving cardiac surgery is older and therefore more prone to cognitive deterioration, these difficulties have declined over the last ten years. It is likely that the multiple changes introduced to cardiac surgery over time have had a cumulative benefit in protecting the brain. The most likely causes of cognitive difficulties are microemboli delivered to the brain during surgery, altered cerebral perfusion and an inflammatory response. The interventions that have been implemented can be divided into those which have attempted to reduce the potential causes of damage and those aimed at reducing the impact by attempting to protect the brain. The evidence for three main types of intervention (equipment, techniques and drugs) is reviewed in this paper. Although many interventions are available only a few have shown a clear benefit. Progress in the future will require larger studies to address this multifactorial problem.

RPR 119990, a novel alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid antagonist: synthesis, pharmacological properties, and activity in an animal model of amyotrophic lateral sclerosis.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonists are of potential interest for the treatment of certain acute and chronic neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we describe the synthesis and pharmacological properties of 9-carboxymethyl-4-oxo-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-2-phosphonic acid (RPR 119990). The compound displaced [3H]AMPA from rat cortex membranes with a K(i) of 107 nM. In oocytes expressing human recombinant AMPA receptors, RPR 119990 depressed ion flux with a K(B) of 71 nM. The antagonist properties of this compound were confirmed on rat native AMPA receptors in cerebella granule neurons in culture and in hippocampal slices where it antagonized electrophysiological responses with IC50 values of 50 and 93 nM, respectively. RPR 119990 antagonized hippocampal evoked responses in vivo, demonstrating brain penetration at active concentrations. RPR 119990 is a potent anticonvulsant in the supramaximal electroshock in the mouse with an ED50 of 2.3 mg/kg 1 h post s.c. administration, giving it a workably long action. Pharmacokinetic studies show good passage into the plasma after subcutaneous administration, whereas brain penetration is low but with slow elimination. This compound was found active in a transgenic mouse model of familial amyotrophic lateral sclerosis (SOD1-G93A) where it was able to improve grip muscle strength and glutamate uptake from spinal synaptosomal preparations, and prolong survival with a daily dose of 3 mg/kg s.c.

The role of apolipoprotein E in cognitive decline after cardiac operation.

BACKGROUND: Recently, Tardiff and colleagues have suggested that the presence of the apolipoprotein E, epsilon4 allele was associated with increased likelihood of cognitive decline after coronary artery bypass grafting. The objective of the current study was to replicate this earlier work using an increased sample size. The increased sample also enabled an analysis by individual genotype in cognitive decline after coronary artery bypass grafting. METHODS: Apolipoprotein E genotyping was performed on 111 individuals undergoing coronary artery bypass grafting. Each participant underwent a battery of nine neuropsychological tests before operation and 4 to 7 weeks after operation. RESULTS: Cognitive decline, assessed by both continuous Z change scores and two categoric measures of cognitive deficit, was not significantly associated with either individual apolipoprotein E genotypes or categorization by the presence or absence of the epsilon4 allele. The examination of potential moderating factors did not alter this finding. CONCLUSIONS: This study suggests that the epsilon4 allele is not associated with cognitive decline in the weeks after coronary artery bypass grafting.

The use of leucocyte-depleting and conventional arterial line filters in cardiac surgery: a systematic review of clinical studies.

Although various forms of arterial line filter have been available for use during cardiopulmonary bypass (CPB) for 30 years, their use is not universal. The aim of this review was to seek evidence of the clinical benefit of using conventional or leucocyte-depleting arterial line filters during bypass. A literature search revealed 28 relevant clinical studies. Despite the wide variety of patient populations, types of filter and outcome measures utilized in studies, a few conclusions are possible. Whereas conventional filtration has the definite effect of reducing neuropsychological deficit post-CPB, the results of studies using the leucocyte-depleting filter are less clear cut. Leucocyte-depleting filters have potential for reducing inflammatory mediated heart and lung injury, however it is recommended that any additional benefit of leucocyte-depleting filters over conventional filters should be further tested by randomized controlled trials of sufficient size.

Cerebral microembolism detected by transcranial Doppler during cardiac procedures.

BACKGROUND AND PURPOSE: Cerebral embolism with clinical sequelae may rarely complicate cardioversion and cardiac catheterization. Transcranial Doppler sonography has recently been introduced to monitor microemboli entering the middle cerebral artery in cardiac and carotid surgery. We therefore used this technique to evaluate the risk of asymptomatic embolism during common cardiac procedures. METHODS: Patients were monitored by transcranial Doppler while undergoing direct current cardioversion (n=15) and cardiac catheterization (n=17). RESULTS: Microemboli were detected in all patients having cardiac catheterization but in only 1 patient after cardioversion. CONCLUSIONS: Microembolism occurred frequently during cardiac catheterization and rarely during cardioversion. It is not yet known whether this has clinical relevance.

Comparison of microembolism detected by transcranial Doppler and neuropsychological sequelae of carotid surgery and percutaneous transluminal angioplasty.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty (PTA) is currently being assessed for the treatment of carotid stenosis. In comparison with carotid endarterectomy (CEA), there is evidence of an increased risk of cerebral microembolism during the procedure. We have sought evidence of any neuropsychological sequelae of carotid PTA and compared it with CEA to demonstrate the relative safety of the 2 treatment options. METHODS: The neuropsychological outcomes after CEA and PTA were compared in 2 matched groups of patients with severe symptomatic carotid stenosis, 96% of whom had been randomized in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), at a single center. Transcranial Doppler insonation of the middle cerebral artery was used to measure cerebral reactivity in response to carbon dioxide inhalation before treatment and then to detect microembolization of the ipsilateral cerebral hemisphere and measure changes in blood flow velocity during the procedures. The performance on a neuropsychological test battery administered before, 6 weeks after, and 6 months after the procedure was compared in 20 patients undergoing PTA and 26 having CEA. RESULTS: At 6 weeks, 5 patients in each group showed a similar decline in neuropsychological performance; global measures showed no significant difference between the 2 procedures, despite a significantly higher incidence of microemboli during PTA. Both groups showed a marked reduction in anxiety after treatment. CONCLUSIONS: The findings provide some reassurance that PTA is not associated with greater cerebral complications than CEA, despite the higher embolic load recorded by transcranial Doppler ultrasonography during angioplasty.

Neuroprotection of the brain during cardiopulmonary bypass: a randomized trial of remacemide during coronary artery bypass in 171 patients.

BACKGROUND AND PURPOSE: Neuropsychological impairment may follow coronary artery bypass surgery as a result of peroperative cerebral microembolism. The hypothesis that remacemide, an NMDA receptor antagonist, would provide protection against such ischemic damage has been tested in a randomized trial. METHODS: One hundred seventy-one patients undergoing coronary artery bypass surgery by a single cardiothoracic surgical team were randomized to receive remacemide (up to 150 mg every 6 hours) or placebo from 4 days before to 5 days after their bypass procedure. Peroperative monitoring included an estimate of the number of microembolic events detected by transcranial Doppler ultrasonography of the middle cerebral artery. A battery of 9 neuropsychological tests was administered before and 8 weeks after surgery. RESULTS: The proportion of patients showing a decline in performance of 1 SD or more in 2 or more tests was reduced in the treated group (9% versus 12%), but this was not statistically significant. On the other hand, overall postoperative change (reflecting learning ability in addition to reduced deficits) was more favorable in the remacemide group, which demonstrated significantly greater improvement in a global z score (P=0.028) and changes in 3 individual tests (P<0.05). The 2 patient groups were well matched, including for the burden of microembolic events. CONCLUSIONS: This is the first study to show statistically significant drug-based neuroprotection during cardiac surgery. In addition to offering improvement in cerebral outcome for such at-risk patients, it supports the hypothesis that drugs acting on the excitotoxic mechanism of ischemic cerebral damage can be effective in humans.

Does being religious help or hinder coping with chronic illness? A critical literature review.

This paper reviews a number of studies relating to religion and coping with chronic illness, emphasizing those aspects relevant to palliative care. After pointing out that religious and existential needs are common in chronic illness, a critical examination is made of those studies which purport to demonstrate associations between spiritual beliefs, religious practices and psychological prognosis. Recommendations are made as to how religious issues can be dealt with in clinical practice, with particular relevance to the multidisciplinary palliative care team.

Particle beam-mass spectrometric analysis of difluorophenyl triazole compounds using normal phase-HPLC.

Normal phase liquid chromatography combined with particle beam mass spectrometry has been applied to the analysis of fluconazole, an anti-fungal agent, [2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-propan-2-ol] and a related intermediate, UK-51060 [2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-ethan-2-one]. Electron ionisation and chemical ionisation have been investigated in combination with quadrupole ion trap and magnetic sector mass spectrometers and the spectra obtained compared with those for direct probe analysis. A novel method for the introduction of the chemical ionisation reagent gas via the interface is described for particle beam-magnetic sector mass spectrometry. Multi-stage scan routines have been implemented on the ion trap for the selective storage of analyte species and removal of solvent ions. Detection limits for both spectrometers have been determined and are discussed in terms of interface geometry and analyte transport characteristics. Normal phase HPLC on silica provided a good separation of the intermediate from the later eluting fluconazole peak.

The short-term impact of Botox injections on speech disability in adductor spasmodic dysphonia.

This study investigates the impact of Botox injections on speech disability in a group of patients with adductor spasmodic dysphonia. Patient-perceived disability was assessed on the Speech Disability Questionnaire. A factor analysis on speech disability yielded five factors. Four of these, social isolation (p < 0.001), negative communication (p < 0.005), public avoidance (p < 0.05) and limited understanding (p < 0.01), showed significant change from prior to and one week post injection. Speech and language therapists' assessment also showed changes in voice quality over the same period. These findings are discussed in terms of the relationship between voice quality, disability and handicap, in adductor spasmodic dysphonia.

Prospective associations between lateralised brain function and immune status in HIV infection: analysis of EEG, cognition and mood over 30 months.

Prospective relations between individual differences in both lateralised neuro-psychophysiological functions and mood ratings with immune status (CD4 and CD8 counts) were examined in asymptomatic HIV-positive men (n = 27) over thirty months. They participated in a controlled study of zidovudine versus placebo (results published elsewhere). Measures included EEG spectra, neuropsychological tests and mood ratings. A model of reciprocal lateralised influences on the immune system was tested whereby patients with left superior to right hemispheric functions were predicted to show a less deleterious outcome than those with the opposite asymmetry pattern. Prospective relations with immune status were found in the EEG with lateralised theta, alpha and beta activity; among cognitive measures with word fluency, semantic processing, and lateralised motor and recognition memory (word/face) processes; with mood ratings including depression, confusion and the total mood score. The nature of the effects supported the laterality predictions. These unique data, showing that neuro-psychophysiological factors in HIV+ but otherwise healthy subjects predict immune competence and compromise present 2-3 years later, warrant replication in a larger cohort.

Anxiety associated with botox injections for adductor spasmodic dysphonia.

This study investigated the relationship between anxiety and Botox injections in a group of patients with adductor spasmodic dysphonia. The aim of the study was to record the course of anxiety using both self report as well as Speech and Language Therapists' evaluation of anxiety. The study confirmed that most patients within the group showed increased anxiety prior to intervention with a gradual decline in the post intervention period. The decline of anxiety seems to reflect the outcome of the procedure rather than the procedure itself. Individual variations and their implications are discussed.

Neurophysiological evaluation of zidovudine in asymptomatic HIV-1 infection: a longitudinal placebo-controlled study.

The effect of early antiretroviral medication with zidovudine on neurophysiological functions was evaluated in subjects with asymptomatic HIV-1 infection. Patients were recruited participants of a larger double-blind randomised placebo-controlled treatment trial with zidovudine (Concorde). The main outcome measures included: quantitative electroencephalography (QEEG), auditory event-related potentials (AEP) and pattern-reversal visual evoked potentials (PRVEP), as well as standard clinical, virological and immunological markers. No significant impairment and no difference between treatment groups was found in visual P100 latency and auditory long-latency P3 responses which is in agreement with the absence of neurological and neuropsychological impairment over the study period. Significant treatment effects were revealed by quantitative electroencephalography (QEEG). While the placebo group showed a significant increase in delta and theta slow frequency QEEG activity over the study period, slow wave amplitude remained unchanged in the zidovudine group after a mean follow-up period of 28 months. In summary, the data provide evidence for a low level neuropathological process in asymptomatic HIV-1 infection which can be effectively suppressed by antiretroviral medication.

Acceptance of zidovudine (AZT) in early HIV disease: the role of health beliefs.

The object of this paper is to explore the health beliefs associated with taking AZT in asymptomatic HIV seropositive individuals. Twenty-eight asymptomatic gay men receiving out-patient care completed self-report questionnaires. Information was gathered on demography, general state of health, health locus of control and health beliefs about AZT therapy. Analyses revealed that 'acceptors' and 'decliners' of early (controversial) medical intervention in HIV disease hold distinctly different beliefs regarding their own health and its relation to treatment. An awareness of the fact that a patient's view of themselves is likely to accord with any action or treatment decision they may have taken, could help to promote a better understanding of why treatment behaviours may or may not appear to be in harmony with the doctors own views and any current medical advice being offered.

Patterns of cognitive asymmetry and syndromes of schizotypal personality.

The Schizotypal Personality Questionnaire, modeled on the nine components of DSM-III-R schizotypy, was administered to 122 medical students along with the Thayer Activation-Deactivation Adjective Checklist and the Warrington Recognition Memory Test for words and faces. Close affinities were found between a three-factor schizotypal personality structure and a three-syndrome model of schizophrenia. Different patterns of cognitive asymmetry (word-face discrepancy scores) were related to Active and Withdrawn syndromes as in schizophrenia, and were related to high activation and general deactivation differences as predicted. A prospective single case study showed that a face-word discrepancy before a first episode of schizophrenia accurately predicted a Withdrawn presenting syndrome. The consistency between syndromes of schizophrenia and schizotypal personality in a normal population suggests possible etiological links between the two, and it supports a dimensional view of psychosis and subclinical predispositions.