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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 325 records · Page 18Linked to original sources
PubMed1995

Vascular reactivity to noradrenaline and neuropeptide Y in the streptozotocin-induced diabetic rat.

The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se. The authors compared non-diabetic rats (n = 9) and rats with streptozotocin-induced diabetes that were either untreated (n = 10), or treated with insulin (n = 9) or food restriction (n = 8) to restore near-normoglycaemia. After 4 weeks of diabetes, contractile responses to noradrenaline (0.24-48 mumol L-1), without and with neuropeptide Y (0.1 mumol L-1), were assessed using an isometric myograph in two mesenteric arteries from each rat. Vessels from untreated diabetic rats were significantly more reactive to noradrenaline than the control vessels when tested without (P < 0.0001) but not with (P = NS) neuropeptide Y. Diabetic rats rendered nearly normoglycaemic through food restriction showed dose-response curves that were very similar to the untreated diabetic group (P = NS). By contrast, insulin-treated diabetic vessels showed reduced sensitivity to noradrenaline, with and without neuropeptide Y, compared with both the diet-restricted and untreated vessels (both P < 0.0001). The authors conclude that vascular sensitivity to noradrenaline, without or with neuropeptide Y, is reduced over a wide dose range in vessels taken from rats treated in vivo with insulin; furthermore, vessels taken from diabetic rats not treated with insulin (hypoinsulinaemic) tended to be more reactive than either control vessels or those taken from the insulin-treated rats. The latter group of rats were probably hyperinsulinaemic for much of the time; the results may therefore support the hypothesis that insulin acts as a vasodilator.

Animals↗
PubMed1995

Effect of sustained physiological hyperinsulinaemia on hypothalamic neuropeptide Y and NPY mRNA levels in the rat.

Neuropeptide Y (NPY) synthesized in the arcuato-paraventricular projection in the rat hypothalamus is thought to play an important role in controlling energy homeostasis. The factors that regulate hypothalamic NPY are not known but, amongst others, insulin has been postulated as an inhibitory modulatory agent. To test this hypothesis, normal male rats were given either insulin (2 units/day) or saline via subcutaneous osmotic minipumps for 3 days. Euglycaemia was maintained by a concomitant glucose infusion in insulin-infused rats which had peripheral insulin levels 5-8 times higher than saline-infused controls. Hyperinsulinaemic rats ate 42% less than controls, but their total energy intake (food intake plus glucose infusion) was higher than that of controls, and they gained more weight than controls during the experimental period. Hyperinsulinaemia had no significant effect on hypothalamic NPY mRNA or NPY levels in the arcuate nucleus. NPY concentrations in the paraventricular nucleus were, however, significantly increased by 73% in hyperinsulinaemic rats, but were closely similar to controls in all other areas. Insulin may act as a satiety factor in that hyperinsulinaemic rats ate less, but the fact that these animals had increased total energy intake and gained excessive weight suggests that insulin may not function as an overall regulator of energy balance. In addition, physiological hyperinsulinaemia does not apparently inhibit NPY gene expression in the arcuate nucleus. Due to the lack of effect of hyperinsulinaemia on NPY synthesis in the arcuate nucleus, the elevated NPY concentrations in the paraventricular nucleus could result from a reduction of its release, which would be in keeping with the reduction in food intake.

Analysis of Variance↗
PubMed1995

Experience with the second generation UroLume prostatic stent.

OBJECTIVE: To assess the efficacy of the new, second generation UroLume (American Medical Systems) prostatic stent. PATIENTS AND METHODS: Forty-seven men with symptomatic and objective evidence of bladder outflow obstruction who were fit for a transurethral resection accepted, as an alternative, the insertion of a new prostatic stent which shortens less than its predecessor. RESULTS: It was possible to insert the stent into 44 of the 47 men. All patients voided spontaneously following stent insertion. Thirty-three patients had their stent inserted either as a day case or with an overnight stay. Six patients were lost to follow-up and two died. Of the remaining 36 patients 22 have now been followed for 2 years, with a mean obstructive score of 1.6 (range 0-12), a mean irritative score of 2.5 (range 0-10) and a mean peak flow of 16.8 mL/s (range 3-31). Fourteen stents had to be removed; in the majority of cases this was because of stent migration or the development of epithelial hyperplasia within the lumen of the stent. CONCLUSION: Because of the development of epithelial hyperplasia and stent migration in approximately one-third of men in this study, a third generation stent has now been developed. Before permanently implanted stents can be recommended for widespread use, the efficacy of new stents should be assessed in specialist units with large numbers of patients and adequate facilities for follow-up.

Aged↗
PubMed1995

Experience with the Memotherm permanently implanted prostatic stent.

OBJECTIVE: To evaluate the Memotherm (Angiomed) permanently implantable prostatic stent. PATIENTS AND METHODS: Forty-eight men (mean age 70.3 years, range 57-86) with symptoms and urodynamics suggestive of bladder outflow obstruction had a Memotherm stent inserted into the prostatic urethra. Subjective and objective follow-up was performed at 1, 3 and 6 months. RESULTS: All but one patient was eventually able to void. Ten stents have been removed and three patients are awaiting stent removal. Subjective benefits bore no correlation with the maximum urinary flow rate and the findings on cystoscopy. Only 15 of the 48 patients had a satisfactory result. CONCLUSION: Permanently implanted prostatic stents should be considered experimental and only marketed after intensive investigation. As a result of this study, the Memotherm stent is to undergo significant modifications.

Aged↗
PubMed1995

Interleukin-1 beta-induced anorexia and pyrexia in rat: relationship to hypothalamic neuropeptide Y.

We investigated the effect of recombinant human interleukin-1 beta (rhIL-1 beta)-induced anorexia and pyrexia on the hypothalamic neuropeptide Y (NPY)-ergic system, which stimulates feeding and reduces thermogenesis. In meal-fed rats, food intake decreased by 83%, 90 min after IL-1 beta treatment (1.3 micrograms/100 g ip; n - 8) vs. controls. NPY concentrations were significantly higher in the medial preoptic area (MPO), paraventricular (PVN), ventromedial (VMN), and dorsomedial (DMN) nuclei but unchanged in the arcuate nucleus (ARC) in both IL-1 beta-treated and pair-fed groups. Indomethacin (0.25 mg/100 g ip) reduced IL-1 beta-induced anorexia and tended to normalize NPY concentrations. In study 2, IL-1 beta increased core temperature by 1.1 degrees C above preinjection values (P < 0.001) and significantly raised NPY concentrations in the MPO, PVN, VMN, and DMN compared with controls, 60 min postinjection. Indomethacin prevented the pyrexia and normalized hypothalamic NPY levels. As NPY concentrations were not increased in the ARC (the hypothalamic site of synthesis), we suggest that the increased NPY levels may result from blocked release, which would be in accord with the known experimental effects of NPY.

Animals↗
PubMed1995

Influence of task demand characteristics on workload and performance.

Two experiments are reported that examined the influence of variation in task demand on performance and workload. The first experiment considered how the manipulation of prior level of task demand affected subsequent workload and performance. The second experiment examined the effects on performance and workload of increments in the level of task demand. Results from the first study indicated that prior level of imposed task difficulty did affect response in a manner consistent with a scaling of workload in relation to previous task conditions. The second study demonstrated the primacy of absolute demand level over increments in that demand as influencing operator response. Overall, our results indicate that workload and performance are sensitive to multiple characteristics of the task and not instantaneous demand level alone. These findings are important in explaining why association and dissociation occur between task demand, operator efficiency, and perceived workload in differing performance contexts. The importance of these findings for the aviation psychologist in assessing pilot and operator workload is articulated.

Adult↗
PubMed1995

The cardiopulmonary cost of backward walking at selected speeds.

Backward walking has been advocated as a method of maintaining cardiovascular conditioning in patients undergoing knee rehabilitation because it may decrease patellofemoral joint compressive forces. The primary purpose of this study was to determine the relationship between the rate of oxygen consumption (VO2) and backward walking speed. Twenty-five healthy males, aged 18-35 years, participated in this study. The rate of oxygen consumption and heart rate were measured at the backward walking speeds of 0.89, 1.12, 1.34, 1.56, and 1.79 m/sec (2.0, 2.5, 3.0, 3.5, and 4.0 miles/hour, respectively). Analysis revealed a direct, curvilinear relationship between VO2 and backward walking speed. This research provides information that can be used to prescribe a backward walking rehabilitation program which may be appropriate to maintain aerobic fitness levels during rehabilitation of patients with patellofemoral pain syndrome.

Adolescent↗
PubMed1995

Regulation of cytokine gene expression: tumor necrosis factor, interleukin-1, and the emerging biology of cytokine receptors.

Cytokines are bioactive molecules which mediate host responses to inflammatory stimuli. For cytokines to exert their effects, a number of molecular processes must occur. Inflammatory cells must sense the presence of a stimulus, often by detection of that stimulus via cell-surface receptors. Information detected at the cell surface must be transduced intracellularly, and the machinery of cytokine messenger RNA and protein synthesis initiated. Once secreted, cytokines must bind specific receptors on target tissues; these receptors in turn transduce signals which alter target cell phenotypes and responses. Each one of these steps is tightly regulated and may serve as a target for therapeutic manipulation. In this article, the regulation of cytokine gene expression is summarized, with particular emphasis on the regulation of tumor necrosis factor alpha and interleukin-1 biosynthesis. Attention is focused on therapeutic agents which alter cytokine production or activity, some of which are currently used in the ICU.

Animals↗
PubMed1995

Postlaryngectomy voice restoration--a 2-year review.

We present a 2-year (1991/92) review of tracheo-oesophageal speech following total laryngectomy with tracheo-oesophageal fistula formation and subsequent use of a voicing prosthesis. Thirty-five primary fistulas and four secondary fistulas were created. Initially, 86% of patients obtained daily use of intelligible, fluent voice with few extraneous stomal sounds. Over a 2-3-month period following surgery, approximately one-third of these lost their fistula speech. The reasons for this were mainly related to psychological and socio-economic factors. Patient selection, surgical technique and postoperative management are described. Although a successful outcome requires a consolidated team approach, primary health care workers also need to know about postlaryngectomy prosthetic (fistula) speech and its management.

Esophagus↗
PubMed1994

Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations.

Megestrol acetate, a synthetic progestogen, stimulates appetite through an unknown mechanism. We tested the hypothesis that it might act, at least in part, by stimulating the activity of hypothalamic pathways containing neuropeptide Y, a potent central appetite stimulant in rats. Administration of megestrol acetate (50 mg/kg/day, n = 8) for 9 days significantly increased food and water intake compared with untreated controls (n = 8). Treated rats showed significant (90-140%) increases in neuropeptide Y concentrations in the arcuate nucleus (where neuropeptide Y is synthesized), in the lateral hypothalamic area (through which arcuate neurones project) and in the medial preoptic area, ventromedial nucleus and dorsomedial nucleus. The latter are sites of neuropeptide Y release and sensitive to neuropeptide Y-induced hyperphagia. Megestrol acetate may therefore stimulate neuropeptide Y synthesis, transport and release, and this could contribute to its appetite-stimulating effects.

Analysis of Variance↗
PubMed1994

Mortality and outcome of patients with brittle diabetes and recurrent ketoacidosis.

The long-term outlook of patients with brittle insulin-dependent diabetes is uncertain. We assessed the outcome of a group of young female patients with diabetes and recurrent ketoacidosis originally investigated in 1979-85 and reassessed after a mean of 10.5 (SD 1.4) years. 7 of the 33 patients could not be traced. 5 (19%) of the remaining 26 had died. Causes of death were not certain, but were probably ketoacidosis (2), hypoglycaemia (2), and renal failure (1). Of the 21 survivors, only 2 (10%) were still considered to have brittle diabetes. Diabetic complications were common (67%), and were more frequent than in a matched control group of stable patients with diabetes (25%). Brittle diabetic patients also had lower quality-of-life scores, more frequent psychosocial disruptions, and were on higher insulin doses (77 [39] vs 47 [15] U per day, p = 0.007) than controls. Pregnancy complications had occurred in 13 of 28 (46%) pregnancies in severely unstable patients compared with 2 of 27 (7%) in stable controls. Patients with brittle diabetes have a tendency to become more stable with time, but have a higher risk of death, more microvascular and pregnancy complications, and a poorer quality of life.

Adolescent↗
PubMed1994

Asymptomatic peripheral nerve dysfunction and vascular reactivity in IDDM patients with and without microalbuminuria.

Abnormal vascular reactivity has been implicated in the aetiology of diabetic microvascular disease and we have previously demonstrated enhanced contractility of hand veins to noradrenaline in insulin-dependent diabetic (IDDM) patients with microalbuminuria. We have now assessed the possible contribution of subclinical peripheral nerve dysfunction to exaggerated vascular reactivity in micro-albuminuric patients. Twenty-five IDDM patients (15 with microalbuminuria), none of whom had symptomatic neuropathy, and 10 control subjects were studied. Vasoconstrictor responses were measured in dorsal hand veins using noradrenaline and phenylephrine. Conduction in median, peroneal and sural nerves was assessed using electrophysiology, and autonomic function using standard cardiovascular reflex tests. The noradrenaline dose causing 50% vasoconstriction was significantly lower in the microalbuminuric diabetic subjects compared with normoalbuminuric (3.6(1.7) mean (SEM) ng/min vs 20.1(6.0) ng/min, p = 0.0002) and non-diabetic subjects (35.1(5.0) ng/min; p < 0.0001). However, reactivity to phenylephrine did not differ between the groups. Median nerve motor conduction velocity was significantly slower in microalbuminuric (48.4(1.4) m/s) than in normoalbuminuric (52.7(1.2) m/s, p = 0.04) and non-diabetic subjects (56.7(0.9) m/s, p = 0.0001). In the diabetic group overall, there was a strongly positive linear correlation between vascular response to noradrenaline and conduction velocity in both the median nerve (r = 0.62, p = 0.0009) and peroneal nerve (r = 0.53, p = 0.006). There was no correlation between phenylephrine-induced responses and motor conduction velocity in either nerve, nor were indices of autonomic function correlated with vascular reactivity to either agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Increased neuropeptide Y concentrations in specific hypothalamic regions of lactating rats: possible relationship to hyperphagia and adaptive changes in energy balance.

Lactation is accompanied by hyperphagia and a reduction in brown adipose tissue (BAT) thermogenesis, which are unexplained. Neuropeptide Y (NPY) powerfully stimulates feeding and inhibits BAT thermogenesis when injected into the paraventricular nucleus and other specific regions of the rat hypothalamus. We have tested the hypothesis that hypothalamic NPY activity is increased in lactating rats. Lactating rats consumed over four times as much food as nonlactating controls (n = 10; p < 0.001). Final plasma insulin concentrations in lactating rats were lower than in controls (6.8 +/- 0.8 vs. 11.7 +/- 2.1 pmol/l; p < 0.05) although plasma glucose and corticosterone concentrations were comparable (p > 0.05). Lactating rats showed significantly higher NPY levels than controls in specific hypothalamic regions, namely the arcuate nucleus-median eminence complex (a 41% rise; p < 0.001), paraventricular nucleus (35%; p < 0.001), ventromedial nucleus (66%; p = 0.003), and dorsomedial nucleus (78%; p < 0.001). Other hypothalamic regions showed no significant differences between groups. Increased NPY concentrations in specific hypothalamic regions, particularly the arcuate nucleus where NPY is synthesized, suggest increased activity of the hypothalamic NPYergic system in lactation. Neuropeptide Y may mediate hyperphagia and reduced BAT thermogenesis in lactation. Hypoinsulinemia may be a stimulus to hypothalamic NPY in lactation, as has been postulated in other conditions of negative energy balance.

Adaptation, Physiological↗
PubMed1994

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial: design and baseline characteristics of participants.

The Nambour Skin Cancer and Actinic Eye Disease Prevention Trial (the Nambour Trial) is a field trial conducted in an unselected adult population in Australia. Using a randomized 2 x 2 factorial design, the principal aim is to evaluate whether regular use of high-protection sunscreen and/or dietary supplementation with beta-carotene (30 mg daily) can alter the incidence rates of basal cell carcinomas and squamous cell carcinomas of the skin over a minimum follow-up time of 4.5 years. Changes in the incidence of solar keratoses and actinic eye disease and the rate of photoaging after intervention will also be investigated. In 1992, 1626 participants between the ages of 25 and 75 years were enrolled, all of whom had been randomly selected from residents of the southeastern Queensland township of Nambour for an earlier skin cancer prevalence survey. This paper describes the background to the trial and its design, with respect to evaluation of effects on actinic skin disease, and documents the baseline characteristics of participants recruited into the Nambour Trial.

Adult↗