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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 73 records · Page 4Linked to original sources

Orexin-A immunoreactive neurons in the rat hypothalamus do not contain neuronal nitric oxide synthase (nNOS).

The lateral hypothalamic area (LHA), a key site involved in the central control of feeding and energy homeostasis, contains populations of neurons that produce the orexin peptides or nitric oxide, two chemical factors that increase food intake. In this study, we used immunohistochemistry to investigate the possibility that rat LHA neurons co-express orexin-A and neuronal nitric oxide synthase (nNOS). The orexin-A and nNOS cell populations in the LHA showed extensive overlap without co-localization, and no evidence of direct anatomic contact was found. The finding that LHA neurons do not co-localize orexin-A and nNOS may suggest that the actions of the orexins and nitric oxide on food intake are mediated via independent mechanisms, however, nitric oxide is a diffusible molecule and could potentially affect the activity of orexin neurons via a non-synaptic mechanism.

Animals↗

Intensity-modulated radiosurgery/radiotherapy using a micromultileaf collimator.

Intensity modulation with inverse treatment planning for 3 clinical stereotactic radiotherapy cases were directly compared against forward planning techniques using beam modification by enhanced dynamic wedge. Dose-volume histogram (DVH) analysis demonstrated that a significant reduction in dose to neighboring critical structures can-be achieved through intensity modulation patterns determined from inverse planning, while a marginal change is achieved in the target volume dose uniformity. This study also demonstrates that the intensity modulated dose patterns generated from inverse planning may differ significantly from the intuitive beam modified patterns developed in the forward planning model. These results suggest that one advantage of intensity modulated radiosurgery/radiotherapy with inverse planning is the significant reduction in dose to normal tissue and critical structures, with its coincident implications for dose escalation studies.

Brain Neoplasms↗

A consensus driven method to measure the required number of intensive care nurses in Australia.

This paper describes a methodology for determining the number of nurses required to staff Australia's intensive care unit (ICU) beds. The evidence used is level IV, that is the use of expert panel opinion, and it is the strongest and most accurate attempt yet to describe how Australia's ICU beds should be staffed with nurses. The researchers provide ratios of staffing applicable to a variety of situations that should be of use to ICU managers and hospital administrators. Equally, the broader calculations explaining the national supply and demand needs provide an easy to use approach and explanation suitable to health professionals, health administrators, policy advisors, governments, politicians and the broader community. Limitations of the approach and further recommendations are made to encourage future work in this area. Finally, a strong correlation between the number of available 'open' ICU beds in Australia and the number of nurses actually working in ICU at any given time is well demonstrated using the methodology outlined in this paper. Clarification of scope and terminology: This paper focuses on the nursing requirements of ICUs only; occasionally we use the word critical care nurse--this generally refers to those nurses who have completed a generic critical care nursing course but who, for the purposes of our study, are working in ICUs. Critical care units encompass ICUs but may also encompass recovery room, cardiothoracic units, coronary care, emergency departments and many other environments where critically ill patients are cared for and treated. This paper does not cover the broader scope of critical care units, only ICUs.

Australia↗

Diet-induced endothelial dysfunction in the rat is independent of the degree of increase in total body weight.

A growing number of studies indicate an association between obesity, insulin resistance, dyslipidaemia and cardiovascular disorders, collectively known as Syndrome X. In this study we have aimed to produce a model of Syndrome X by voluntary feeding of Wistar rats with a highly palatable cafeteria diet, and examined its effects on metabolic changes and vascular reactivity of Wistar rats. At the end of the experiment, the cafeteria-diet fed group was divided into two groups of low weight gain (LWG) and high weight gain (HWG). Both LWG and HWG groups had significantly (P<0.01) higher fat-pad mass than their chow-fed counterparts, while gastrocnemius muscle mass were comparable. All cafeteria-diet fed rats had significantly (P<0.01) raised plasma triacylglycerol (TG) levels whereas plasma non-esterified fatty acids, glucose and insulin levels were similar between chow-fed and cafeteria-diet fed rats. Vasorelaxation responses to acteylcholine, insulin and sodium nitroprusside were significantly (P<0.01) attenuated in cafeteria-diet fed animals; however, there were no differences in contractile responses of the mesenteric arteries to noradrenaline or KCl between the groups. Multiple regression analysis showed a significant (P<0.05) negative association between plasma TG levels and reduction in acetylcholine-induced vasorelaxation. Acetylcholine-induced vasorelaxation was also significantly (P<0.05) associated with the amount of fat-pad mass. These data suggest that diet-induced vascular dysfunction can occur in the absence of insulin resistance, and that plasma TGs may have a detrimental effect on vascular reactivity.

Animals↗

Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols.

Impaired arterial vasorelaxation, due primarily to endothelial dysfunction, is associated with obesity. To clarify the relationship with insulin resistance and other metabolic disturbances, we studied endothelial-dependent and -independent vascular responses in rats with dietary-induced obesity. Dietary-obese rats had significantly higher body weights (10-32%; P<0.001) and fat-pad masses (220-280%; P<0.001) than lean controls, together with raised plasma levels of triacylglycerols (15-80%; P<0.001), non-esterified fatty acids (13-38%; P<0.05) and leptin (85-180%; P<0.001). However, measures of insulin sensitivity (including the hyperinsulinaemic-euglycaemic clamp in a parallel experiment) were comparable with those in controls. Contractions induced in mesenteric arteries by noradrenaline (0.5-8 micromol/l) were comparable in lean and obese groups, but vasorelaxation in noradrenaline-preconstricted arteries was markedly reduced in dietary-obese rats of both sexes. Concentration-response curves to endothelium-dependent vasorelaxants (acetylcholine, A23187 and insulin) showed significant reductions in maximal relaxation (20-95% less than in leans; P<0.001) and significant rightward shifts in EC(40) (concentration giving 40% of maximal response) (P<0.01). Relaxation in response to the direct NO donor, sodium nitroprusside, showed a lesser impairment (12%; P<0.01) in dietary-obese rats. Maximal relaxation to acetylcholine was correlated inversely in both sexes with fat-pad mass (r(2)=0.37, P<0.05) and plasma triacylglycerols (r(2)=0.51, P<0.01), and with leptin in males only (r(2)=0.35, P<0.05). Independent determinants of acetylcholine-induced relaxation were fat mass and plasma triacylglycerols; plasma insulin and insulin sensitivity had no effect. Dietary-induced obesity severely impaired arterial relaxation in both sexes, particularly at the endothelial level. This is not attributable to insulin resistance, but may be related to moderate hypertriglyceridaemia.

Analysis of Variance↗

Interleukin 4 content in chronic lymphocytic leukaemia (CLL) B cells and blood CD8+ T cells from B-CLL patients: impact on clonal B-cell apoptosis.

B-chronic lymphocytic leukaemia (CLL) clonal B cells are characterized by resistance to apoptosis. We evaluated clonal B cells and blood T cells for interleukin 4 (IL-4) content as IL-4 is able to increase CLL cell resistance to apoptosis. The content of IL-4 in CD8+ T cells of CLL patients (n = 9) ranged from 37% to 63% of the total CD8+ T cells (mean level of 49% +/- 3.4) compared with a range of 5-10% for control CD8+ T cells. Clonal B cells positive for cytoplasmic IL-4 ranged from 1% to 97% (mean value 57.8 +/- 6.9%). CD8+ T cells and clonal B cells secreted detectable levels of IL-4, but only clonal CLL B cells (n = 4) secreted IL-4 in association with increasing cell numbers. Fludarabine (F-ara-AMP, 0.1-100 micromol/ml) was able to downregulate the IL-4 content of CD8+ T cells, but not clonal B-cell IL-4. Culture supernatant from CLL CD8+ T cells decreased the spontaneous apoptotic rate of clonal B cells that was reversed with anti-IL-4 and soluble IL-4 receptor. These findings show that IL-4 is present in the microenvironment of B-CLL. In addition, use of agents that can interfere with IL-4 presentation to clonal B cells can be effective in increasing clonal B-cell apoptosis.

Antineoplastic Agents↗

Vasorelaxant effects of oestradiols on guinea pigs: a role for gender differences.

Various studies have shown vasorelaxation properties for 17alpha- and 17beta-oestradiol. Here, we studied the effects of gender difference as well as oestrous cycle on oestradiol-induced vasorelaxation in mesenteric arteries from male and female guinea-pigs and in main uterine arteries from female guinea-pigs in vitro. Both 17alpha- and 17beta-oestradiol (0.5-20 micromol L-1) induced concentration-dependent relaxation of both mesenteric and uterine arteries preconstricted with either noradrenaline (NA; 10 micromol L-1) or KCl (125 mmol L-1) from both day-7 and day-15 female guinea-pigs. 17beta-oestradiol was more potent in relaxing arteries precontracted with NA than those pretreated with KCl, while 17alpha-oestradiol was more effective in relaxing those arteries precontracted with KCl. In mesenteric arteries from male animals, 17alpha-oestradiol was significantly (P < 0.001) more potent on arteries precontracted with NA than KCl, an effect opposite to that seen on arteries from female animals. However, both 17alpha- and 17beta-oestradiol were more potent in relaxing arteries from male animals compared with their female counterparts. These data indicate a possible role for gender differences in the vascular effects of oestradiols.

Abdomen↗

Effects of short-term feeding of a highly palatable diet on vascular reactivity in rats.

BACKGROUND: Numerous studies have shown that long-term consumption of high-fat, high-energy diet results in obesity, which in turn, leads to cardiovascular disorders. However, there is little or no data on the acute effects of a highly palatable diet on vascular function. MATERIAL AND METHODS: In this study we aimed to evaluate the changes in metabolic and vascular reactivity in Wistar rats fed a palatable diet for 2 days. RESULTS: Two-days feeding of rats with a palatable diet did not effect body weight, fat-pad mass or gastrocnemius muscles weights. Nor there were any changes in plasma glucose, insulin or leptin levels. However, compared with chow-fed rats, palatable diet-fed rats had significantly raised plasma free fatty acids and triglycerides levels (for both, P < 0.01). Compared with chow-fed animals, vasorelaxation responses to carbamylcholine and sodium nitroprusside were significantly attenuated in palatable diet-fed rats (for both, P < 0.01). However, there were no differences in histamine-induced vasorelaxation between chow-fed and palatable diet-fed rats. CONCLUSION: These data indicates that diet-induced endothelium-dependent and -independent vascular dysfunction occurs long before obesity develops.

Aldehydes↗

Worldwide overview of critical care nursing organizations and their activities.

While critical care has been a specialty within nursing for almost 50 years, with many countries having professional organizations representing these nurses, it is only recently that the formation of an international society has been considered. A three-phased study was planned: the aim of the first phase was to identify critical care organizations worldwide; the aim of the second was to describe the characteristics of these organizations, including their issues and activities; and the aim of the third was to plan for an international society, if international support was evident. In the first phase, contacts in 44 countries were identified using a number of strategies. In the second phase, 24 (55%) countries responded to a survey about their organizations. Common issues for critical care nurses were identified, including concerns over staffing levels, working conditions, educational programme standards and wages. Critical care nursing organizations were generally favourable towards the notion of establishing a World Federation of their respective societies. Some of the important issues that will need to be addressed in the lead up to the formation of such a federation are now being considered.

Critical Care↗

Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y.

Weight loss normally stimulates hunger, through mechanisms that include falls in circulating leptin and insulin, leading to stimulation of hypothalamic neuropeptide Y (NPY). Here, we investigated the leptin, insulin and NPY to clarify why hunger is suppressed in mice with severe cachexia due to the MAC16 adenocarcinoma. MAC16-bearing mice progressively lost weight (19% below controls) and fat (- 61%) over 16 days after tumour transplantation, while total food intake fell by 10%. Pair-fed mice showed less wasting, with final weight being 9% and fat mass 25% below controls. Plasma leptin fell by 85% in MAC16 and 51% in pair-fed mice, in proportion to loss of fat. Plasma insulin was also reduced by 49% in MAC16 and 53% in pair-fed groups. Hypothalamic leptin receptor (OB-Rb) mRNA was significantly increased in both MAC16 (+ 223%) and pair-fed (+192%) mice. Hypothalamic NPY mRNA was also significantly raised in MAC16 (+152%) and pair-fed (+ 99%) groups, showing negative correlations with plasma leptin and insulin, and a positive association with OB-Rb mRNA. In MAC16-induced cachexia, leptin production and hypothalamic OB-Rb and NPY expression are regulated appropriately in response to fat depletion. Therefore, suppression of hunger is probably due to tumour products that inhibit NPY transport or release, or that interfere with neuronal targets downstream of NPY.

Adenocarcinoma↗

Antibiotics for the prevention of urinary tract infection in children: A systematic review of randomized controlled trials.

OBJECTIVE: The objective was to evaluate the effectiveness of low-dose, long-term antibiotics for the prevention of symptomatic urinary tract infection (UTI) in children. DESIGN: This was a systematic review of randomized controlled trials with a random effects model meta-analysis. PARTICIPANTS: Five trials involving 463 children were performed. RESULTS: Three trials (n = 392) evaluated the effectiveness of long treatment courses of antibiotics (2 to 6 months) for children with acute UTI to prevent subsequent, off-treatment infection. Only 2 trials (n = 71) evaluated the effectiveness of long-term, low-dose antibiotics to prevent on-treatment UTI. Very few of the children enrolled in the trials were boys, had abnormal renal tracts, or were infants. The trial quality was poor, with a lack of blinding, and unstated UTI definitions were almost universal. Long-term antibiotic administration reduced the risk of UTI with treatment (relative risk 0.31, 95% confidence limits 0.10 to 1.00), but there was significant heterogeneity (Q = 13.45, P <.01), and there was no sustained benefit once antibiotics had ceased (relative risk 0.79, 0.61 to 1.02). CONCLUSIONS: Methodologic and applicability problems with published trials mean that there is considerable uncertainty about whether long-term, low-dose antibiotic administration prevents UTI in children. Well-designed, randomized, placebo-controlled trials are still required to evaluate this commonly used intervention.

Anti-Bacterial Agents↗

Validity of motor tasks for predicting running ability in acquired brain injury.

INTRODUCTION: Rehabilitation of running following traumatic brain injury (TBI) has the potential to enhance quality of life. Retraining of running following TBI has not been previously reported in the literature. In response to a lack of information about which motor tasks should be included in a retraining programme, this study aimed to investigate performance predictors of running ability. METHOD: Forty TBI subjects (20 runners and 20 non-runners) performed four specific motor tasks which were selected on the basis of theory and clinical experience with TBI subjects. The four tasks included bounding onto a leg, walking on toes, stepping backwards up a step, and balancing on one leg. Subjects were generally extremely severely brain damaged (median post-traumatic amnesia >28 days), had suffered multiple leg fractures and had received greater than 8 months rehabilitation. RESULTS: The four motor tasks differentiated significantly between the two groups (p < 0.001) and were all strong predictors of running ability. The presence of a non-support phase (NSP) during the bounding task was the strongest predictor of running ability. Logistic regression indicated that TBI subjects who could execute a NSP into a single bound were 24.6 times more likely to be able to run than subjects who could not. When the four tasks were used in combination, two tasks were identified by logistic regression: (1) ability to execute a free-float phase during a bound, and (2) balancing on one leg. All four motor tasks had high retest reliability, with proportional indices of reliability ranging from 0.92-0.97. No statistically significant difference was found between runners and non-runners for group characteristics such as age, severity of injury (length of PTA), orthopaedic leg injuries and time post-injury (p > 0.05). These characteristics were not shown to influence the ability to run following TBI. CLINICAL IMPLICATIONS: The four motor tasks were strong predictors of running ability. Severity and type of injury were not factors influencing ability to run. This study provides preliminary evidence about the motor tasks which have the potential to be used in a running programme. No casual relationship has been identified. The next step is to investigate whether training in these tasks is effective in the rehabilitation of running following TBI.

Adult↗

Congenital heart disease in Papua New Guinean children.

The aim of the study was to analyse critically the programme for surgical management of children in Papua New Guinea (PNG) with congenital heart disease. A hospital record-based analysis was undertaken to document the pattern, management and short-term outcome of surgery in PNG children referred with a diagnosis of congenital heart disease to the Royal Alexandra Hospital for Children in Sydney, Australia. On admission, physical examination, chest radiogram, electrocardiogram, cross-sectional echocardiogram and, in most cases, cardiac catheterization were performed. Of the 170 children referred over the 17-year period, 1978-1994, 165 were confirmed to have congenital heart disease and were included in the study. Their ages ranged from 2 months to 16 years (median 5.5) and the male to female ratio was 1:1. One-sixth had delayed milestones and one-fifth long-term wasting. A large number were tachypnoeic, in heart failure or had pulmonary hypertension on admission. Ventricular septal defect, 34%, tetralogy of Fallot, 23%, and patent ductus arteriosus, 16.4%, were the predominant defects. lesions such as aortic stenosis, coarctation of the aorta and transposition of the great arteries are under-represented. Altogether, 133 children (81%) had surgery; 75% were open- and 25% closed-heart operations. The complications were unremarkable and the mortality rate (6%) acceptable for the era. The programme was therefore very successful for a small proportion of children born in PNG with congenital heart disease.

Adolescent↗