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Biomedical subjects

P Buckley

Publications and source records attributed to P Buckley.

At least 19 recordsLinked to original sources

Identifying some determinants of "jet lag" and its symptoms: a study of athletes and other travellers.

BACKGROUND: Travelling across multiple time zones disrupts normal circadian rhythms and induces "jet lag". Possible effects of this on training and performance in athletes were concerns before the Sydney Olympic Games. OBJECTIVE: To identify some determinants of jet lag and its symptoms. METHODS: A mixture of athletes, their coaches, and academics attending a conference (n = 85) was studied during their flights from the United Kingdom to Australia (two flights with a one hour stopover in Singapore), and for the first six days in Australia. Subjects differed in age, sex, chronotype, flexibility of sleeping habits, feelings of languor, fitness, time of arrival in Australia, and whether or not they had previous experience of travel to Australia. These variables and whether the body clock adjusted to new local time by phase advance or delay were tested as predictors for jet lag and some of its symptoms by stepwise multiple regression analyses. RESULTS: The amount of sleep in the first flight was significantly greater in those who had left the United Kingdom in the evening than the morning (medians of 5.5 hours and 1.5 hours respectively; p = 0.0002, Mann-Whitney), whereas there was no significant difference on the second flight (2.5 hours v 2.8 hours; p = 0.72). Only the severity of jet lag and assessments of sleep and fatigue were commonly predicted significantly (p<0.05) by regression analysis, and then by only some of the variables. Thus increasing age and a later time of arrival in Australia were associated with less jet lag and fatigue, and previous experience of travel to Australia was associated with an earlier time of getting to sleep. Subjects who had adjusted by phase advance suffered worse jet lag during the 5th and 6th days in Australia. CONCLUSIONS: These results indicate the importance of an appropriate choice of itinerary and lifestyle for reducing the negative effects of jet lag in athletes and others who wish to perform optimally in the new time zone.

Adult↗

Enteral versus parenteral nutrition: a pragmatic study.

Controversy persists as to the optimal means of providing adjuvant nutritional support. The aim of this study was to compare enteral nutrition (EN) and parenteral nutrition (TPN) in terms of adequacy of nutritional intake, septic and nonseptic morbidity, and mortality. This was a prospective pragmatic study, whereby the route of delivery of nutritional support was determined by the attending clinician's assessment of gastrointestinal function. Patients considered to have inadequate gastrointestinal function were given TPN (group 1), while those deemed to have a functioning gastrointestinal tract received EN (group 2). Patients in whom there was reasonable doubt as to the adequacy of intestinal function were randomized to receive either TPN (group 3) or EN (group 4). The trial setting was a large district general hospital with a dedicated nutrition team. A total of 562 patients were included in the study (331 males; median age 67 y). Gastrointestinal function on entry into the study was considered inadequate in 267 patients who were given TPN (group 1) and adequate in 231 whom received EN (group 2). There was clinical uncertainty about the adequacy of gut function in 64 patients (11.4%) who were randomized to receive either TPN (group 3, 32 patients) or EN (group 4, 32 patients). The incidence of inadequate nutritional intake was significantly higher in group 4 compared with group 3 (78.1% versus 25%, P < 0.001). Complications related to the delivery system and other feed-related morbidity were significantly more frequent in both EN groups compared with the respective TPN groups. EN was associated with a higher overall mortality in both nonrandomized and randomized patients. There were no significant differences observed in the incidences of septic morbidity between patients receiving TPN and those given EN. EN is associated with a higher incidence of inadequate nutritional intake, complications related to the delivery system, and other feed-related morbidity than TPN. There is no evidence from this study to support a difference between the two modalities in terms of septic morbidity. Patients in whom there is reasonable doubt as to the adequacy of gastrointestinal function should be fed by the parenteral route.

Adult↗

Are there hangover-effects on physical performance when melatonin is ingested by athletes before nocturnal sleep?

Athletes ingest melatonin in an attempt to improve sleep quality or alleviate symptoms of jet lag after transmeridian travel. It is not known whether there are residual effects of this hormone on physical performance in fit subjects. After a sample size estimation involving a meaningful effect on performance of 5%, five milligrams of melatonin or placebo were ingested by twelve physically-active subjects before sleep in a double-blind experiment. The following morning, subjective sleep quality (latency and maintenance) were measured together with intra-aural temperature, grip strength of the left and right hands, and time to complete a 4 km time trial on a cycle ergometer. The subjects also rated perceived exertion during the latter test. The null hypothesis of no effect of melatonin on either subjective sleep quality or physical performance measured the morning after administration could not be rejected on the basis of our observations (P > 0.30). The mean differences between treatments were less than 1% for the strength tests and time trial performance. The confidence intervals for these differences for left and right grip strength and the cycling test were - 2.1 to 2.8 kg, - 3.1 to 2.7 kg and -3.0 to 4.5 s, respectively. In conclusion, it is unlikely that 5 mg of melatonin would have any meaningful effects on physical performance in the morning after fit subjects ingest the hormone. There was also little evidence that it improves sleep quality in this population. Further research is needed concerning the effects of daytime and nighttime admistration of melatonin on performance, in both situations of normal and disturbed sleep.

Adult↗

When symptoms persist: clozapine augmentation strategies.

Recent data and clinical experience confirm that, in spite of superior efficacy for treatment-refractory schizophrenia, a substantial proportion of patients receiving clozapine will continue to experience disabling symptoms. Optimizing clozapine monotherapy is the first step in the management of "clozapine nonresponders." Described here is a synthesis of the available literature on the range and efficacy of clozapine augmentation strategies that may be used when monotherapy fails. Treatment options include adjunctive antipsychotic medications, mood stabilizers, selective serotonin reuptake inhibitors, glycinergic agents, and electroconvulsive therapy. The evidence favoring one augmentation strategy over another is lacking; overall, adjunctive therapy is associated with only modest clinical improvement. Moreover, case series and open-labeled clinical trials dominate the extant literature, and there is a dearth of double-blind trials comparing these augmentation agents. Current systematic efforts to enhance the treatment of these patients with adjunctive therapies are worthy of being studied in carefully conducted clinical trials.

Antipsychotic Agents↗

Linking cardiovascular theory to practice in an undergraduate medical curriculum.

Case-based teaching (CBT) tutorials were introduced by the Physiology Department at Adelaide University to bridge the gap between theory and practice in the early years of undergraduate medical education. With the use of a clinical case-based environment, CBT aimed to achieve integration of structure-function relationships and an increase in students' capacity to apply a physiological understanding to clinical observations/symptoms and data. With peer-peer interactions in small groups, students could trial history taking and examination skills, interpret common investigations, and relate their findings to an understanding of structure and function. Here, the cardiovascular tutorials highlight the centrality of an understanding of structure and function in the evaluation of a case of syncope. An independent evaluation of the students' learning experience demonstrated that CBT tutorials were successful in their aims. The "hands-on" experience was highly rated, with students reporting that the CBT approach gave relevance to structure and function. Whatever the curriculum learning style, underpinning practice with an understanding of theory remains a desirable feature of medical education.

Cardiovascular Physiological Phenomena↗

If patients with schizophrenia have small brains, why don't they have small heads?

Although patients with schizophrenia have reduced brain size, there is no conclusive evidence that they have reduced head size. This begs the question: 'What is the precise relationship between head size and brain size?' We used a unique osteological collection to explore the relationship between external head measures and cranial capacity. The external measures accounted for, at most, 60% of the variance in cranial capacity - a value low enough to question the oft-assumed tight relationship between head measures and brain size. Obviously, various tissues and spaces [skull, sinus, muscle (frontalis, temporalis and occipitalis), subcutaneous fat and epidermal layers] contribute to head size without contributing to brain volume. The contribution of these other tissues and spaces tends to decrease the signal and increase the noise in the estimation of brain volume. Thus, it is understandable that patients with schizophrenia can have reduced cranial capacity and not reduced head size.

Adult↗

The trouble with kidneys derived from the non heart-beating donor: a single center 10-year experience.

BACKGROUND: The demand for renal transplantation has increasingly outstripped the supply of donor organs especially over the past 10 years. Although related and unrelated live donation is being promoted as one option for increasing the donor pool, it is unlikely that this will in itself be able to bridge the gap. Non-heart beating donors (NHBD) can provide an alternative supply of organs, which should substantially increase the donor pool. METHODS: In Newcastle, NHBD kidneys have been used for transplantation for a period of 10 years. In the early period (1988-1993) excellent results were obtained (90.5% success); however, these donors were controlled NHBD, Maastricht category III. In the second phase (1994-1998) increasing numbers of donors were obtained from the Accident and Emergency Department unit. These were failed resuscitation for cardiac arrest (category II). The rates of success in this period were poor (45.5% success) and the program was halted. The third phase of the program used machine perfusion of the kidneys and glutathione S transferase enzyme analysis to assess viability. RESULTS: Using such approaches renal transplants from largely category II donors produced a success rate of 92.3% which was significantly better than the phase II period of the program (P=0.023, Fisher two-tail test). CONCLUSION: Machine perfusion and viability assessment of NHB kidneys in phase III of the program has increased our donor pool as well as improved the graft survival. This is particularly relevant for the use of the category II NHB donor where the incidence of primary nonfunction was high, illustrated by phase II where machine perfusion/viability assessment was not used.

Adult↗

Early results of a non-heartbeating donor (NHBD) programme with machine perfusion.

Freeman Hospital, Newcastle upon Tyne restarted their non-heartbeating donor (NHBD) programme in September 1998 using machine perfusion, due to early poor results with conventional cold storage (45% graft survival, phase II). Since then, 15 NHBD kidneys have been transplanted. The retrieval protocol consisted of in situ perfusion with a double balloon triple lumen cannula in Maastricht category II male donors age range 13-59 years. Mean primary warm ischaemic time was 24.8 min (range 10-44). All kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of total GST (maximum acceptable limit of 200 units/l) and intrarenal vascular resistance (IRVR) was recorded. Fifteen of the 22 kidneys (68.62%) were transplanted. Delayed graft function (DGF) was seen in ten recipients (66.6%), two kidneys had immediate function (IF), one organ was exported, two recipients died of unrelated causes and a further seven kidneys were discarded (two had high tGST, two were infected and three had poor flow characteristics). In phase III, a success rate of 91.7% was thus achieved, which was better than the phase II period (P = 0.027, Fisher 2-tail test). Machine perfusion has been successfully introduced in phase III to the Newcastle NHBD programme and facilitates viability assessment of NHBD kidneys.

Adolescent↗

Bed sharing patterns in a cohort of Australian infants during the first six months after birth.

OBJECTIVE: To measure bed sharing (BS) activity in healthy term infants. METHODOLOGY: The sleep-wake behaviour and place of infant sleep were recorded for infants aged between 2 and 24 weeks. Infants were then identified as BS or non bed sharing (NBS) according to each of four different definitions of bed sharing. RESULTS: The mean proportion of infants who spent any time BS during a 24-h period was significantly greater (P < 0.05) between 2 and 12 weeks (40.9 +/- 1. 4%) than between 13 and 24 weeks (36.5 +/- 1.5%). A significantly greater proportion (P < 0.005) of infants bed shared for more than 2 h (25 +/- 1%) than for either 1-2 h (10.5 +/- 1.1%) or for less than 1 h/24 h (3.2 +/- 0.5%) during the whole study period. Each of the definitions of BS used in the study separated infants on the basis of the amount and frequency of BS activity. CONCLUSION: : Bed sharing activity was common and varied in this cohort. It was possible, using quantitative definitions, to identify those infants who routinely bed share.

Australia↗

Admissions, length of stay, and medication use among women in an acute care state psychiatric facility.

OBJECTIVE: Despite growing numbers of elderly persons with serious mental illness such as schizophrenia, little research has been conducted on the manifestation of serious mental illness in later life, and our understanding of the mental health care needs of this population is limited. This study examined length of stay and medication use among women age 50 and older admitted to an acute care state psychiatric facility. METHODS: A computerized record search for all women discharged from a large urban state psychiatric facility over a one-year period was undertaken. Demographic and resource utilization data, including total length of stay and pharmacy utilization, were obtained from the hospital database. RESULTS: The database search produced the records of 564 women, with a mean age of 37.5 years. Women constituted 60 percent of patients over age 50. The mean length of stay was 16.1 days for the entire group; for women under age 50 (N=492), mean length of stay was 15 days, and for women age 50 and older (N=72), it was 23.1 days (p=. 01). Among those age 50 and older, 58.3 percent had a diagnosis of schizophrenia or schizoaffective disorder, compared with only 38 percent of those under age 50. CONCLUSIONS: Our data suggest that women constitute the majority of patients over age 50 in a state psychiatric facility and that they have longer stays than younger women.

Acute Disease↗

Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals.

A workshop was held to critically discuss the need for a nonrodent species and the role of the dog in regulatory toxicity testing of pharmaceuticals; to discuss opportunities to reduce and refine the use of dogs in preclinical toxicology; and to identify a number of specific recommendations which could be feasibly achieved to move the process forward. To facilitate a preliminary evaluation of the contribution of dog studies to the risk assessment process, anonymised, unpublished data were provided from fully evaluated, repeat-dose toxicity studies in the rat and dog. Results of the International Life Sciences Institute (ILSI) Human Toxicity Project were also presented and discussed. Analysis of the data demonstrated that the dog can provide additional toxicity information, which, in some cases, was shown to be predictive for humans. Discussions indicated that there is potential for achieving a reduction in dog use and several possible approaches were identified. To further the progress of this initiative, there is a need to collate the results of pharmacology, toxicology, and clinical studies to address some of the proposed approaches. One of the outcomes of the workshop will be the establishment of a steering group to co-ordinate data collation for further analysis.

Animal Testing Alternatives↗

Assessment of non-heart-beating donor (NHBD) kidneys for viability on machine perfusion.

UNLABELLED: The shortage of organs has resulted in renewed interest in organs from non-heart-beating donors (NHBD). Viability assessment of such organs may reduce the incidence of delayed graft function and primary non-function. In Phase III of the NHBD programme, introduction of machine perfusion enabled the assessment of these marginal donors. Since then the graft survival has been 88.4% compared with the previous phase where machine perfusion or viability assessment was not done (45.5%). The parameters used were total glutathione S-transferase (GST) in the perfusate, the intrarenal vascular resistance (IRVR) and flow characteristics over time. METHODS: All NHBD kidneys were machine perfused through a locally developed perfusion system. The viability was assessed by serial measurements of the above-mentioned parameters. RESULTS: Forty-two local NHBD kidneys were retrieved and one kidney was imported, of which 19 donors (i.e. 38 kidneys) were of the uncontrolled (category II) donors. After viability assessment on machine perfusion; two kidneys were discarded due to positive tests for syphilis, four kidneys had high total GST levels, five kidneys due to high IRVR and poor flow characteristics and one did not flush on retrieval. Three kidneys were exported after viability tests. In 28 NHBD kidney recipients, immediate graft function was seen in two kidneys, 22 (84.6%) developed delayed graft function. One kidney had primary non-function, and two recipients lost their grafts, due to chronic rejection and renal vein thrombosis. There were two deaths, unrelated to transplantation. Graft survival was achieved in 88.4% (23/26 graft survival in phase III) of cases. CONCLUSION: Machine perfusion and assessment of NHBD kidneys has been successfully introduced to the Newcastle NHBD programme. This approach, using renal transplants from largely category II donors produced a success rate of 88.4% which was significantly better than the phase II period (45.5%) of the program (p=0.023, Fisher 2 tail test).

Humans↗

Neutrophil gelatinase-associated lipocalin in normal and neoplastic human tissues. Cell type-specific pattern of expression.

Neutrophil gelatinase-associated lipocalin (NGAL) has recently been identified in myeloperoxidase-negative neutrophil granules. Members of the lipocalin family are thought to bind and transport small lipophilic molecules such as retinoids and roles in cell regulation have been proposed. Recently, NGAL has also been demonstrated in the colonic mucosa in certain pathologic conditions. The aim of this study was to examine the distribution of NGAL in normal and neoplastic tissues by immunohistochemistry. Interestingly, NGAL was found in a variety of normal and pathological human tissues. A cell type-specific pattern of expression was seen in bronchus, stomach, small intestine, pancreas, kidney, prostate gland, and thymus. The comparative analysis of the putative rat homologue neu-related lipocalin showed a very similar pattern of expression with the exception of pancreas and kidney. Neoplastic human tissues showed a very heterogeneous expression of NGAL protein. High NGAL levels were found in adenocarcinomas of lung, colon and pancreas. In contrast, renal cell carcinomas of various subtypes and prostate cancers contained low NGAL levels. Lymphomas and thymic tumours were negative for NGAL immuno-labeling. Knowledge about the location of NGAL in normal cells and in disease states provides the first clues towards understanding its biological function.

Acute-Phase Proteins↗