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Biomedical subjects

M McCarthy

Publications and source records attributed to M McCarthy.

At least 19 recordsLinked to original sources

The Pliocene paradox (mechanisms for a permanent El Niño).

During the early Pliocene, 5 to 3 million years ago, globally averaged temperatures were substantially higher than they are today, even though the external factors that determine climate were essentially the same. In the tropics, El Niño was continual (or "permanent") rather than intermittent. The appearance of northern continental glaciers, and of cold surface waters in oceanic upwelling zones in low latitudes (both coastal and equatorial), signaled the termination of those warm climate conditions and the end of permanent El Niño. This led to the amplification of obliquity (but not precession) cycles in equatorial sea surface temperatures and in global ice volume, with the former leading the latter by several thousand years. A possible explanation is that the gradual shoaling of the oceanic thermocline reached a threshold around 3 million years ago, when the winds started bringing cold waters to the surface in low latitudes. This introduced feedbacks involving ocean-atmosphere interactions that, along with ice-albedo feedbacks, amplified obliquity cycles. A future melting of glaciers, changes in the hydrological cycle, and a deepening of the thermocline could restore the warm conditions of the early Pliocene.

Journal Article↗

Predicting drug-resistant patients who respond to add-on therapy with levetiracetam.

INTRODUCTION: Levetiracetam (LEV) is approved for use as add-on therapy in adult patients with partial epilepsy. It is apparent from clinical trials that up to 8% of previously drug-resistant patients may be rendered seizure-free by adding-on levetiracetam. As yet there is no way of predicting these unexpectedly responsive patients. We set out to identify our previously refractory patients who had demonstrated unexpected responsiveness to add-on therapy with levetiracetam, and compared these to patients who had not responded to the drug. We then attempted to characterise any clinical features that differentiated these groups of patients. METHODS: We included all patients with a history of present or previous exposure to levetiracetam who had been unresponsive to at least two other prior anti-epileptic drugs (AEDs) and recorded their demographic and clinical data. We divided response into (a) 'seizure-free' (seizure-free for a minimum of 6 months after commencing LEV); (b) 'partial > 50%' (greater than 50% reduction in seizures for a minimum of 6 months after commencing LEV); (c) 'honeymoon' (seizure-free for less than 6 months after commencing LEV and then returned towards baseline frequency); and (d) 'no-response'. For the purpose of analysis we considered the 'seizure-free' and 'partial > 50%' groups as 'responders', and the 'no response' group as 'non responders'. RESULTS: 344 patients were included in the analysis. Fifty-six patients (16.3%) were rendered seizure-free on levetiracetam. Idiopathic generalised epilepsy and post-traumatic partial epilepsy were more common in the responder than the non-responder group (p = 0.005 and 0.05 respectively). Lamotrigine was used significantly more often in combination with levetiracetam in responders than non-responders (p = 0.003). The mean daily dose of levetiracetam was lower in responders than non-responders. DISCUSSION: A higher than expected number of previously drug resistant patients was rendered seizure-free by add-on therapy with levetiracetam. Those who respond best appear to do so at relatively low doses and our data suggest the possibility of a beneficial pharmacodynamic interaction between levetiracetam and lamotrigine. We were unable to identify any clinical factors that clearly predicted which patients would become seizure-free and we hypothesise that response may be determined by genetic or molecular factors. All drug-resistant patients, including those being assessed for surgery, should be considered for a trial of levetiracetam, regardless of their epilepsy classification.

Anticonvulsants↗

Sampling period determination for heart rate logging under an exercise regimen.

Using a mathematical procedure, we determine appropriate sampling rates for logging heart rate, at a variety of exercise intensities. The mathematical procedure involves correlating exercise and heart rate data to determine a dynamical mathematical model, from which the frequency response of the relationship between exercise intensity and heart rate can be determined. The sampling rate is then straightforwardly deduced by making appropriate measurements on the frequency response curve. We show how careful consideration needs to be given to the choice of dynamical model structure and the work regimen, so that consistent and convincing conclusions can be drawn. We demonstrate that the dynamics of the work-rate/heart-rate system are dependent on the nominal work/heart rate, but a 5-s sampling period, as used in many commercial heart rate monitors, appears to be adequate, especially when some averaging is performed before logging.

Adult↗

Physiological responses of Bos taurus and Bos indicus cattle to prolonged, continuous heat and humidity.

Two experiments were conducted to investigate the physiological responses of Bos taurus (Angus cross, n = 6) and Bos indicus (Brahman, n = 6) cattle to prolonged heat and humidity, as can occur during live export by sea. Each experiment was carried out in climate-controlled rooms, where heifers were exposed to 15 d of sustained heat and humidity. The treatment was designed to be representative of a long-haul, live-export voyage leaving a southern Australian winter and traveling to a Middle Eastern summer. Wet bulb temperature (WBT) was used to give a combined measure of dry bulb temperature and relative humidity and was increased over several days, culminating in 5 d at 32 degrees C WBT between d 7 and 11. By d 11, the respiratory rate and core body temperature increased (P < 0.001) compared with values at lower ambient temperature on d 1 and 2 when climate-controlled rooms were not operating. Feed intake of Bos taurus was reduced (P < 0.001) by d 11, whereas that of Bos indicus did not change (P = 0.14). Despite no diurnal variation in climatic conditions, core body temperature of both Bos taurus and Bos indicus continued to show a circadian amplitude of approximately 1 degrees C throughout the hottest period. This amplitude increased during the recovery period after heat was removed (up to 1.8 degrees C for Bos indicus and 1.6 degrees C for Bos taurus). Water intake for both Bos taurus and Bos indicus increased when WBT increased (P < 0.01 on d 11). Significant acid-base and blood electrolyte imbalances occurred in both Bos taurus and Bos indicus, with changes in Bos taurus being more substantial and prolonged. The increase in respiratory rate coincided with a decrease in the partial pressures of carbon dioxide and bicarbonate in venous blood. However, during the hottest period, average daily venous blood pH remained unchanged. When the heat load was reduced after d 11, the blood pH decreased, indicating metabolic acidosis. Blood pH declined from 7.44 to 7.36 for Bos taurus (P < 0.001) and from 7.44 to 7.38 for Bos indicus (P < 0.001). Other parameters measured include heart rate; packed cell volume; plasma and urine Na, K, and Cl; urine pH; and specific gravity. Our results suggest that Bos taurus cattle experience significant physiological changes during exposure to prolonged and continuous high heat and humidity, with alterations persisting for some days after the heat-stress conditions subside. Bos indicus experience similar but less pronounced physiological changes.

Acclimatization↗

Modality-specific aspects of sustained and divided attentional performance in multiple sclerosis.

While the prevalence of cognitive impairment in multiple sclerosis is well documented, few studies have systematically investigated the profile of attentional abilities. In the current study, 30 MS participants were assessed on measures of sustained and divided attention and compared to a sample of 30 neurologically intact healthy controls. Performance on visual and auditory unimodal and bimodal trials were conducted for measures of both forms of attention. A three-factor mixed measures analysis of variance (groupxtaskxmodality) was conducted. MS participants were impaired relative to controls on all measures of speed and accuracy across unimodal and bimodal trials and more impaired on measures of divided attention than on sustained attention measures. Performance on the bimodal trials was also significantly compromised relative to the unimodal trials especially on the divided attention task. The theoretical and clinical implications of these findings are discussed.

Acoustic Stimulation↗

Factors influencing consumption of pork and poultry in the Irish market.

Comparisons of Irish consumers' beliefs about pork and poultry in the framework of Fishbein and Ajzen's Theory of Reasoned Action (TRA) showed that poultry is viewed as the tastier, healthier and less expensive of the two meats while pork is viewed as the safer meat. The influence of attitudes and important others on intention to consume these meats was explored and the findings support the basic structure of the TRA model. In this study, both attitudes towards poultry and pork consumption and the influence of important others influenced intention to consume pork and poultry, but attitude was of greater importance. For poultry, health, eating enjoyment, safety and price were most important determinants of attitude with environment and animal welfare less so. In the case of pork, health, eating enjoyment, safety and animal welfare were most important determinants of attitude with environment and price less so. Furthermore, doctor's advice influenced the subject norm for both poultry and pork, which in turn influenced intention to consume, while dietician's advice only influenced the subject norm for pork.

Adult↗

Epilepsy in the United Kingdom: seizure frequency and severity, anti-epileptic drug utilization and impact on life in 1652 people with epilepsy.

OBJECTIVES: To describe the clinical characteristics of epilepsy in a representative sample of the UK population, including seizure frequency and severity; overall severity of epilepsy; patterns of anti-epileptic drug (AED) use; and the impact of epilepsy on patients' lives. Secondly, to determine if these characteristics differ according to age. METHOD: A large, geographically comprehensive survey of people with epilepsy by means of a postal questionnaire distributed by general practitioners to 3455 unselected patients receiving AEDs for epilepsy, regardless of age or type of epilepsy and including all regions of the UK. Data were collected on age and gender; age of onset of seizures; seizure frequency and severity; AED use and adverse effect levels; and impact on life of epilepsy. Sub-analyses were performed with stratification by epilepsy severity and age-group. RESULTS: There were 1652 completed replies. The mean age was 44.2 years; there were 47.2% males, 48.5% females (4.4% not recorded). The mean age at first seizure, 25.1 years, and the mean duration of epilepsy, 19.7 years, were comparable with previous studies. In the preceding one year, 51.7% of patients had no seizures; 7.9% one seizure, 17.2% 2-9 seizures and 23.2% 10 or more. Sixty-four percent of patients had epilepsy classified as mild and 32% severe. There was a marked and significant decrement of seizure frequency with increasing age. The most commonly used AEDs were carbamazepine (37.4%), valproate (35.7%), phenytoin (29.4%), phenobarbitone or primidone (14.2%) and lamotrigine (10.3%). Monotherapy was used in 68% of patients. Patients taking multiple AEDs reported significantly higher levels of adverse effects and worse seizure control. The major impacts of epilepsy on life were work and school difficulties, driving prohibition, psychological and social life. The impacts listed varied with the epilepsy severity and age. CONCLUSIONS: Seizures remain uncontrolled in up to half of all people with epilepsy in the UK with significant impact on work, family and social life. Previously, there has been a deficiency of data on the characteristics of epilepsy in older people, although it is recognized that the condition is of increasing epidemiological importance in this age group. We have found clear differences in the clinical characteristics of epilepsy in older people, particularly that seizure frequency appears to decline with increasing age.

Adult↗

MRI and plain radiography in the assessment of displaced fractures of the waist of the carpal scaphoid.

We treated 50 patients with fractures of the waist of the scaphoid in a below-elbow plaster cast for up to 13 weeks. Displacement of the fragments was assessed independently by two observers using MRI and radiographs performed within two weeks of injury. The MRI assessments showed that only the measurement of sagittal translation of the fragments and an overall assessment of displacement had satisfactory inter- and intra-observer reproducibility and revealed that nine of the 50 fractures were displaced. Only three of the 49 fractures with adequate follow-up failed to unite, and all were displaced with more than 1 mm of translation in the sagittal plane. If the MRI assessment of displacement of the fracture was used as the measurement of choice, assessment of displacement on the initial scaphoid series of radiographs showed a sensitivity of between 33% and 47% and a positive predictive value of between 27% and 86%. Neither observer was able correctly to identify more than 33% to 47% of the displaced fractures from the plain radiographs. Although the overall assessment of displacement and gapping and translation in the coronal plane on the plain radiographs influenced the rate of union, none of these parameters identified all three fractures which failed to unite. We conclude that the assessment of displacement of scaphoid fractures on MRI can probably be used to assess the likelihood of union although the small number of nonunions limits the power of the study. In contrast, the assessment of displacement on routine radiography is inaccurate and of less value in predicting union.

Casts, Surgical↗

Thrombolytic therapy for myocardial infarction facilitated by mobile coronary care.

BACKGROUND: The benefit of Thrombolytic Therapy (TT) for acute myocardial infarction is time sensitive. In Northern Ireland widespread availability of mobile coronary care units facilitates delivery of TT to heart attack victims. This region-wide prospective observational study assessed the efficacy of various methods of delivery of TT. METHODS: All 15 acute hospitals providing acute coronary care in Northern Ireland participated and data were collected prospectively over six months on all patients admitted with acute myocardial infarction or who received TT. The information was analysed regarding appropriateness of TT, methods and timeliness of delivery of TT and mortality rates. Performance was measured against National Service Framework standards. FINDINGS: Of 1638 patients with acute myocardial infarction 584 were considered eligible for TT and 494 (85 %) received it, in addition to 18 patients without infarction. Of the 512 thrombolysed patients 282 (55%) were treated in hospital coronary care units, 131 (26%) were treated pre-hospital, 97 (19%) in accident and emergency departments, and two in general medical wards. Overall median call-to-needle time was 87 (7-1110) mins and this was shortest for pre-hospital treatment when 55% of call-to-needle times were < or = 60 mins. For patients treated in hospital median door-to-needle time was 46 (0-1065) mins and this was shortest when TT was administered by accident and emergency staff, when 65% of door-to-needle times were < or = 30 mins. In patients with ST elevation myocardial infarction TT was associated with lower mortality, especially when administered pre-hospital. INTERPRETATION: NSF targets for TT are unlikely to be met in Northern Ireland without increasing pre-hospital delivery of TT and by improving collaboration between coronary care and accident and emergency staff with TT availability in accident and emergency departments.

Aged↗

CD4+ and CD8+ cells accumulate in the brains of acquired immunodeficiency syndrome patients with human immunodeficiency virus encephalitis.

To test the hypothesis that CD4+ T lymphocytes accumulate in brains of end-stage acquired immunodeficiency syndrome (AIDS) patients, we examined T-lymphocyte subsets in the CA1, CA3, and CA4 regions of the hippocampus of AIDS patients with (n = 10) and without (n = 11) human immunodeficiency virus encephalitis (HIVE) plus controls (n = 7). HIV p24 antigen was common in monocytic cells and rare in activated/memory CD45RO+ lymphocytes. Hippocampal activated/memory CD45RO+ T lymphocytes significantly increased (P <.001) in seven of the eight hippocampal subregions with hippocampal HIVE (1.14 +/- 1.4 T cells/high-power field [hpf]), but AIDS hippocampus without HIVE were similar to controls (0.03 +/- 0.07 T cells/hpf and 0.03 +/- 0.09 T cells/hpf, respectively). CD45RO+ and CD3+ lymphocytes were similar in numbers and distribution, whereas CD4+ and CD8+ lymphocytes were weakly immunoreactive and less frequent. All four lymphocyte subtypes were present in perivascular spaces and microglial nodules of HIVE, and had direct contact with neurons. Monocytes, microglia, and multinucleated giant cells were immunoreactive for CD4 in AIDS cases with hippocampal HIVE but microglia in remaining AIDS cases and controls were CD4-. CD68+ macrophages significantly increased in hippocampus of HIVE patients (P <.05) and were predominately perivascular in the absence of local HIVE. These studies show that CD4+ T lymphocytes, as well as CD8+ T lymphocytes, participate in the local inflammatory response of HIVE in end-stage AIDS patients, and suggest that their recruitment requires local HIV infection. The perineuronal location of CD4+ cells provides the potential for lymphocyte-mediated neuronal injury or trans-receptor-mediated neuronal infection.

AIDS Dementia Complex↗

Line bisection in normal adults: direction of attentional bias for near and far space.

The direction of attentional bias in forty normal adults was assessed using a computer generated line bisection task. A 4 (viewing distance)x4 (line length)x2 (cursor starting position) repeated measures factorial design was employed. As predicted, differences in bisection performance as a function of viewing distance were observed. The findings confirmed that scanning direction (contingent upon the starting position of the cursor), but not line length, significantly modulated this effect. The direction of bias across near and far space was further clarified yielding a progressive shift from a leftward bias in near space to a rightward bias in far space. A significant interaction of distance, line length and starting position revealed differential effects for left and right starting positions as a function of viewing distance and line length. More specifically, a leftward start witnessed deviations shifting progressively from left-to-right as distance and line length increased though no comparable pattern was observed for rightward starts. The results provide important behavioural support for the suggestion that dissociated neural systems may be responsible for attending and acting in near and far space and that other lateralised functions (such as scanning strategies) can influence hemispheric activation. The findings have relevant theoretical implications as well as important implications for the clinical assessment of unilateral neglect using a standard line bisection task, both of which are discussed.

Adolescent↗

Information recalled by women taking anti-epileptic drugs for epilepsy: a questionnaire study.

Women with epilepsy have different needs from men, particularly associated with childbearing. Despite clinical guidelines, the care of women with epilepsy remains suboptimal. The aim of this study was to establish whether women with epilepsy recall being given information on topics relating to childbearing. Design of study and methods included a postal questionnaire study of 795 women with epilepsy and of childbearing age. The respondents were identified through both general practices and hospital clinics as part of the Clinical Standards Advisory Group study into Epilepsy Services. Of those women who considered the questions personally relevant, 38-48% recalled receiving information about contraception, pre-pregnancy planning, folic acid and teratogenicity, with lower overall proportions among adolescent women. The proportions that recalled receiving information about vitamin K, safety in child-care and breast-feeding were lower at 12, 24 and 24%, respectively. While it is recognised that information provided may not be recalled, our results suggest that further measures are required to improve the effectiveness of information provision in the UK in relation to women of childbearing age with epilepsy.

Adolescent↗

A health impact assessment model for environmental changes attributable to development projects.

STUDY OBJECTIVE: European Union legislation requires large industrial and civil development projects to undergo environmental impact assessment. The study objective was to identify environmental health risk estimates for these developments from the epidemiological literature and to develop, and apply these within, a mathematical health impact assessment model. DESIGN AND RESULTS: In the UK, good practice guidelines have set out environmental issues to be considered in development projects, but little attention is given to direct health effects. Broad quantifiable risks were identified for four-air, chemicals, noise, and road traffic-of 14 standard environmental effects. A mathematical model was constructed that is based on people moving between different health states over their lifetime. Age related hazard functions are applied to cause specific measures of mortality and morbidity. A hypothetical example for a development creating air and chemical pollutants is given. CONCLUSIONS: A mathematical model applying epidemiological risks to an exposed population can provide quantification of environmental health effects. The approach may in future find application during project development, and by public health regulatory authorities for environmental health impact assessment.

Air Pollution↗