Biomedical subjects
Publications and source records attributed to J Graham.
All three simulated loci influencing the quantitative variables Q1, Q2 and Q3 were successfully mapped by using a strategy of covariate adjustment and segregation analysis, coupled with association analyses and lod-score analyses.
The prevalence and causes of 'burnout' and psychiatric disorder among senior oncologists and palliative care specialists have been measured in a national questionnaire-based survey. All consultant non-surgical oncologists in the UK were asked to participate. Sources of work-related stress and satisfaction were measured using study-specific questions which were aggregated into factors. Psychiatric disorder was estimated using the 12-item General Health Questionnaire. The three components of 'burnout'--emotional exhaustion, depersonalisation and low personal accomplishment--were assessed using the Maslach Burnout Inventory. Three hundred and ninety-three out of 476 (83%) consultants returned their questionnaires. The estimated prevalence of psychiatric disorder in cancer clinicians was 28%, and this is similar to the rate among British junior house officers. The study group had equivalent levels of emotional exhaustion and low personal accomplishment to those found in American doctors and nurses, but lower levels of depersonalisation. Among cancer clinicians, 'burnout' was more prevalent among clinical oncologists than among medical oncologists and palliative care specialists. Psychiatric disorder was independently associated with the stress of feeling overloaded (P < 0.0001), dealing with treatment toxicity/errors (P < 0.004) and deriving little satisfaction from professional status/esteem (P = 0.002). 'Burnout' was also related to these factors, and in addition was associated with high stress and low satisfaction from dealing with patients, and with low satisfaction from having adequate resources (each at a level of P < or = 0.002). Clinicians who felt insufficiently trained in communication and management skills had significantly higher levels of distress than those who felt sufficiently trained. If 'burnout' and psychiatric disorder among cancer clinicians are to be reduced, increased resources will be required to lessen overload and to improve training in communication and management skills.
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Carotid endarterectomy if advised for asymptomatic disease must be associated with a low peri-operative morbidity and mortality and satisfactory long-term results. Over a 12 year period between 1978-1989 181 carotid endarterectomies were performed on 163 patients with asymptomatic carotid artery stenosis. There were 112 males and 51 females with a mean age of 64.9 years. All patients had a high-grade lesion (> 70% stenosis). The combined operative mortality and stroke rate was 2.8%. On long-term follow up six patients suffered a stroke. Only one patient however sustained a stroke in the same territory as the previously operated carotid artery. Four years following surgery 78% of patients were alive. Carotid restenosis or occlusion occurred in 8.3% of the remaining patients, all of whom were asymptomatic. All the immediate postoperative strokes occurred in patients with severe bilateral carotid artery disease. These patients with severe bilateral disease appear to constitute a high risk sub-group for peri-operative stroke. The role of 'normal pressure-hyperperfusion breakthrough' syndrome as the presumed aetiology of two of the postoperative cerebral haemorrhages is discussed.
Extreme heart-rate lability accompanies the air-breathing cycles of Synbranchus marmoratus and Monopterus albus. When air is taken into the buccopharyngeal air-breathing organ of these fishes, heart rate increases sharply above pre-inspiration rates of 3­25 beats min-1 to as high as 40­45 beats min-1. With time, and as O2 is depleted from the air-breathing organ, heart rate gradually declines and drops to its lowest level with, or following, exhalation. Relationships between air breathing and sinus arrhythmia in M. albus were investigated by injecting variable gas volumes and O2 mixtures into the cannulated air-breathing organ. Tests were also carried out on undisturbed fish breathing volitionally in atmospheres containing different O2 levels. Both the volume and O2 content of the inspired gas affect the level and duration of inspiration tachycardia. Additional factors affecting tachycardia are the heart rate prior to inspiration and the time since air was last held. S. marmoratus is a non-obligatory air breather and uses rhythmic branchial aquatic respiration to a greater extent than M. albus, an obligate air breather. While the heart rates of both species are increased during aquatic ventilation, the higher heart rate to ventilation ratio in S. marmoratus (2­3 versus approximately 1 in M. albus) seems attributable to its more proficient aquatic respiratory system. The available cardiorespiratory data for air-breathing fishes indicate that the scope of air-inspiration tachycardia is smaller in lungfishes and other primitive species than in most teleosts. This difference is mainly attributable to the greater chronotropic effect of sympathetic cardiac innervation in teleosts.
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To audit the referral decisions made by a single cardiologist for coronary angiography after exercise testing, we retrospectively reviewed the charts of 303 consecutive patients in a community hospital. The outcomes of these decisions, in terms of angiograms performed and quality-adjusted life expectancy gains as predicted by a decision analysis model, were compared with the theoretical decisions that would have been made using the model. The 97 patients sent for angiography exercised for a shorter time (5.6 +/- 3.1 vs. 6.9 +/- 3.2 min, p < 0.001) had more ST deviation (2.7 +/- 1.4 vs. 1.7 +/- 1.0 mm, p < 0.001), more angina (53.6 vs. 36.9% of patients, p < 0.01) and were more likely to have had a previous myocardial infarction (59.8 vs. 33.5% of patients, p < 0.001) than the 206 not referred. However, of those not referred, 137 were each predicted to gain up to 5.7 quality-adjusted life years (QALYs) from bypass surgery. The overall predicted gain from the cardiologist's decisions was only 0.1 +/- 2.5 QALYs/patient. Had the decisions been made using the model, the mean gain would have been 1.9 +/- 1.3 QALYs/patient, and an extra 128 patients would have been sent for angiography. Decision analysis makes consistent decisions with defined risks and benefits. Such decisions can be reproduced, reviewed and analysed, whereas traditional decision-making may inconsistently reflect the clinician's beliefs and values.
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The physical and biological properties of Iodixanol, a new nonionic density gradient medium, are described in this paper. It is effectively a dimer of Nycodenz and it exhibits two significant advantages over previous iodinated density gradient media--its aqueous solutions are iso-osmotic up to a density of 1.32 g/ml and it is capable of forming self-generating gradients in 1 to 3 h. It has a very low toxicity toward biological material and enzyme assays can be carried out in its presence.
This paper reports the use of a new density gradient compound, Iodixanol, for the resolution of the major organelles from mouse liver. A major advantage of Iodixanol over other iodinated density gradient media is its ready ability to form self-generated gradients. Gradient-forming conditions have been modulated to provide optimal recoveries of Golgi membranes, lysosomes, mitochondria, and peroxisomes. The organelles were isolated in high yield (80-90% of gradient input) and high purity. Nycodenz and Iodixanol were compared using preformed gradients. Iodixanol provided resolution superior to that of Nycodenz, notably of peroxisomes and mitochondria and the separation of lysosomes from endoplasmic reticulum. Because Iodixanol does not interfere significantly with marker enzyme activities, gradient fractions can be analyzed without removal of the gradient medium.
In order to evaluate the influence of dopaminergic transmission on regional brain utilization of serotonin (5HT), the effects of the destruction of the ascending dopamine (DA) pathways on regional brain 5HT metabolism in the rat were examined. Complete unilateral lesions of the nigrostriatal DA pathways (> 90% DA loss) were made by infusing the neurotoxin 6-hydroxy-dopamine into either the left medial forebrain bundle (MFB) or the left substantia nigra (SN). At 6 weeks after the lesions, levels of 5HT and its major metabolite, 5-hydroxyindoleacetic acid (5HIAA), were determined bilaterally in the striatum, frontal cortex, and hypothalamus. In the striatum of the lesioned hemisphere, the 5HT level decreased by more than 50%, while the ratio of 5HIAA:5HT (an index of 5HT turnover) increased by more than 90%. In the same rats, cortical and hypothalamic 5HT, 5HIAA, and 5HT turnover were not changed as a result of the MFB or SN lesions. These results suggest that the loss of DA innervation in the striatum triggers an increase in 5HT turnover and a net depletion of 5HT in the striatum. To verify that the loss of DA was responsible for the observed striatal 5HT changes, we examined the effect of intracerebral implantation of DA-containing pellets into one group of MFB-lesioned rats. The lesioned rats with placebo pellets did not differ from lesioned rats without pellets, whereas the implantation of DA pellets reversed the lesion-induced changes in the 5HT levels and 5HIAA:5HT ratios.(ABSTRACT TRUNCATED AT 250 WORDS)
This study examines the effect of a 6 month dietary supplement of either gamma-linolenic acid (GLA) or eicosapentaenoic acid (EPA) on the synthesis of prostaglandins E2 and F2 alpha by the endometrium of women with regular menstrual cycles. Samples of endometrium, obtained pre- and post-treatment, were incubated in vitro for 2 h and the prostaglandins E2 and F2 alpha released into the medium measured by radioimmunoassay. The ability of the tissue to take up 14C-arachidonic acid before and after treatment was also examined. Both GLA and EPA caused a marked decrease in the synthesis of prostaglandins E2 and F2 alpha (P < 0.001) but under the experimental conditions used, there was no consistent effect on arachidonic acid uptake. Body mass index, serum testosterone, fasting insulin and serum sex hormone-binding globulin (SHBG) concentrations did not change during the 6 month treatment period. An effect of GLA and EPA on arachidonic acid uptake into endometrial tissue explants was demonstrated in vitro. In the presence of both GLA and EPA, uptake into phospholipids (particularly phosphatidylcholine) decreased while uptake into triglycerides increased. Free 14C-arachidonic acid levels (that which could not be removed from the tissue by washing) also increased. Suppression of endometrial prostaglandin E2 and F2 alpha synthesis following GLA or EPA supplementation can be explained as direct competition between these fatty acids and arachidonic acid (the precursor of 2-series prostaglandins) for incorporation into membrane phospholipids. The amount of arachidonic acid available for 2-series prostaglandin synthesis will therefore be reduced. However, other mechanisms may exist which need to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
Reflective practice offers a way to structure learning within supervision by paying attention to aspects of practice within reflected experiences, in such ways that the issues can be identified, understood, and worked through to resolve contradictions between desired outcomes and actual practice. In this process, emerging personal knowledge of practice is juxtaposed with relevant theory in such a way that the manager is able to meaningfully assimilate theory into his or her practice as appropriate. This paper illustrates how an H-grade unit nurse manager identified a number of situational management issues through reflecting and sharing experiences in a group clinical supervision milieu (over a period of 15 weeks). Clinical supervision is being advocated as a means to ensure practitioner development of effective practice (Vision for the Future, Department of Health 1993).
The metabolic rates (V(dot)O2) of three tropical tunas [yellowfin tuna (Thunnus albacares), kawakawa (Euthynnus affinis) and skipjack (Katsuwonus pelamis)] were estimated using a large water-tunnel respirometer. Experiments lasting up to 31 h were used to determine the effects of velocity (U) on tuna V(dot)O2 over a range of U (17-150 cm s-1) and temperatures (18­30°C). Replicate tests were carried out on several fish. The swimming V(dot)O2 of yellowfin is temperature-dependent (Q10=1.67, determined over intervals of 3­5°C). For yellowfin and skipjack, it was also possible to partition metabolic costs between maintenance and locomotion. The standard metabolic rate (SV(dot)O2) was estimated by extrapolation of the U/V(dot)O2 function to U=0. Comparisons of SV(dot)O2 for different size groups of yellowfin show that the mass-specific scaling exponent for V(dot)O2 is -0.40. The SV(dot)O2 of tuna is comparable to values determined previously by stasis respirometry and is approximately three times higher than that of salmonids. Further comparisons with salmonids show that the slope of the U/V(dot)O2 function is less for tunas, which demonstrate a greater swimming efficiency.
The body temperatures (Tb) of nine yellowfin tuna (Thunnus albacares) were monitored while fish swam in a large water tunnel at controlled velocities (U) and ambient temperatures (Ta). Monitoring Tb during step changes in Ta at constant U permitted estimation of the thermal rate coefficient (k), an index of heat transfer. In the yellowfin, k is dependent on both Ta and the direction of the thermal gradient (i.e. whether Ta is greater or less than Tb). Modulation of k in response to Ta was further demonstrated during tests in which U was varied; the elevation of Tb in response to equal increases in U was 3­4 times less at 30 C than at 25 and 20 C. These experiments demonstrate that the yellowfin tuna can modulate heat transfer. This ability could prevent overheating during intense activity, retard heat loss during a descent into cool water and permit increased heat gain upon returning to warm surface waters (i.e. when Tb<Ta).
Yellowfin tuna (Thunnus albacares) swimming kinematics was studied in a large water tunnel at controlled swimming velocities (U). Quantified kinematic variables included the tail-beat frequency, stride length (l), caudal amplitude, yaw, the propulsive wavelength, the speed of the propulsive wave (C) and the sweepback angle of the pectoral fins. In general, all variables, except the propulsive wavelength and consequently C, are comparable to values determined for other teleosts. The propulsive wavelength for the tunas (1.23­1.29 L, where L is fork length) is 30­60 % longer than in other cruise-adapted teleosts such as salmonids. The resulting thunniform swimming mode and the morphological and anatomical adaptations associated with the long propulsive wavelength (e.g. fusiform body shape, rigid vertebral column) act to minimize anterior resistance and maximize caudal thrust. The long propulsive wavelength also increases the maximum l which, in concert with the elevated muscle temperatures of tunas, increases their maximum swimming velocity.
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The effects of N omega-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase (1,5, and 10 mg/kg) on vasopressor and depressor responses to segmental sympathetic nerve stimulation were studied in the pithed rat preparation. Vasopressor responses were evoked by stimulation of the spinal sympathetic outflow at T6-T8 (30 V, 0.05 ms at 5 Hz with 10 pulses). This pressor response was biphasic: An initial transient response (to nerve stimulation) was followed by a later prolonged response (to adrenal catecholamine release). L-NAME 1, 5, and 10 mg/kg increased mean arterial blood pressure (MAP); this effect was maximal at 1 mg/kg L-NAME, but had no effect on heart rate (HR). L-NAME 1, 5, and 10 mg/kg potentiated both phases of the pressor response; the effect was maximal at 10 mg/kg. Vasodepressor responses were evoked by stimulation of the spinal sympathetic outflow at S2-L6 (30 V, 0.05 ms at 5 Hz with 10 pulses). L-NAME 1, 5, and 10 mg/kg did not inhibit these depressor responses. We conclude that inhibition of the synthesis of endogenous NO causes a hypertension in pithed rats that is associated with increased vasoconstriction in response to sympathetic nerve stimulation and adrenal catecholamine release. Systemic vascular depressor responses to segmental sympathetic nerve stimulation are not affected, however; therefore, NO cannot be the major mediator of these responses.