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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 37 records · Page 2Linked to original sources
PubMed2004

Beliefs and practices of patients with advanced cancer: implications for communication.

The aim of this study was to investigate the beliefs that patients with advanced cancer held about the curability of their cancer, their use of alternatives to conventional medical treatment, and their need to have control over decisions about treatment. Of 149 patients who fulfilled the criteria for participation and completed a self-administered questionnaire, 45 patients (31%) believed their cancer was incurable, 61 (42%) were uncertain and 39 (27%) believed their cancer was curable. The index of need for control over treatment decisions was low in 53 patients (35.6%) and high in only 17 patients (11.4%). Committed users of alternatives to conventional medical treatments were more likely to believe that their cancer was curable (P<0.001) and to have a higher need for control over decisions about treatment (P<0.004). The mean need for control scores were highest in patients who believed that their cancer was curable, or who were uncertain about the curability of their cancer, but who acknowledged that their oncologist had reported that the cancer was incurable. The diverse beliefs, attitudes and actions of these patients were consistent with a range of psychological adaptations to a life-threatening illness, some realistic and others illusory. Illusory responses influence what communication can achieve in daily oncology practice.

Attitude of Health Personnel↗
PubMed2004

Illusions in advanced cancer: the effect of belief systems and attitudes on quality of life.

Patients with advanced cancer frequently express positive attitudes and can be unduly optimistic about the potential benefits of treatment. In order to evaluate an illusory domain in the context of advanced cancer, we developed a scale of will to live and characterized the beliefs that patients held about the curability of their cancer, and how committed they were to using alternative treatments. A measure of quality of life was used as the dependent variable in order to assess the association between these attributes. After a preliminary exploration confirmed the presence of an illusory domain, these concepts were prospectively tested in 149 ambulant patients with advanced cancer who attended for palliative systemic treatment, radiation treatment or supportive care. The scale of global quality of life was reliable (Cronbach's alpha coefficient 0.72). The distribution of the scores of will to live was skewed, with no respondent scoring poorly, and the scale was reliable (Cronbach's alpha coefficient 0.82). The scale of belief in curability showed diverse beliefs. In some cases, there was a discrepancy between respondents' beliefs in curability and what they believed to be the report by their doctors. There was also an association between a committed use of alternative treatments and a belief in the curability of the cancer (p<0.001). In a multiple regression analysis, both will to live and performance status remained associated with better quality of life scores after adjustment for other relevant variables (p<0.05 and <0.001, respectively). These results suggest that positive illusory beliefs can be measured and are an important component of adaption for some patients with advanced cancer. Furthermore, this illusory domain may influence the perception and measurement of quality of life.

Adaptation, Psychological↗
PubMed2004

Evaluation of femur length during the second and third trimesters in fetuses with myelomeningocele.

OBJECTIVES: To determine if the femur length of fetuses with myelomeningocele is shorter in the second and third trimesters compared with that of normal fetuses. METHODS: We retrospectively collected measurements of femur length, head circumference, biparietal diameter and abdominal circumference from detailed obstetric ultrasound studies performed during the second and third trimesters in 31 fetuses with myelomeningocele and 43 fetuses with no detectable anomaly. The gestational age predicted by each parameter (based on Hadlock's tables) was compared with the true gestational age (based on last menstrual period), using the ANCOVA test to determine if there was a statistically significant difference between the two groups of fetuses. RESULTS: There was no significant difference in femur length (P = 0.60) or in abdominal circumference (P = 0.85) between fetuses with myelomeningocele and normal fetuses. Fetuses with myelomeningocele did have a significantly lower biparietal diameter and head circumference (P < or = 0.001). CONCLUSIONS: Myelomeningocele is not associated with reduced femur length in the second and third trimesters, suggesting that the known postnatal lower extremity foreshortening in patients with myelomeningocele develops late in gestation or after birth.

Case-Control Studies↗
PubMed2004

Evaluation of a porcine origin acellular dermal matrix and small intestinal submucosa as dermal replacements in preventing secondary skin graft contraction.

The degree to which a split thickness skin graft (STSG) contracts after application to its recipient bed is related in part to the proportion of the dermis harvested from the donor site. Harvesting thicker skin grafts may produce better cosmetic results in the recipient bed but result in increased donor site morbidity. The combination of an autologous ultra thin split thickness graft with an underlying non-autologous dermal component may reduce secondary skin graft contraction without further increasing donor site morbidity. This study was aimed at assessing the suitability of two porcine derived biomaterials (Permacol and small intestinal submucosa, SIS) for use in combination with skin grafts in a Sprague-Dawley rat model. Full thickness wounds (1 cm(2)) were created in Sprague-Dawley rats and grafted with skin in combination with Permacol or SIS either as a one-stage operation or following a 2-week-period of vascularisation of these dermal matrices before a second stage operation to cover with skin. Skin graft viability and wound area were assessed at weekly intervals until 4 weeks after graft application. Both Permacol and SIS were able to support an overlying skin graft but had no beneficial effect on skin graft contraction in this model compared to skin grafts alone.

Animals↗
PubMed2004

The diamond CO2 laser as a method of improving the vascularisation of a permanent collagen implant.

For a biomaterial to be considered as anything other than a simple filler material it must allow a certain degree of ingrowth from the surrounding host tissues. Permacol is a novel porcine derived biomaterial that is isocynate crosslinked to prevent its degradation in vivo, but while it appears to be biocompatible in terms of its histological tissue response, our early studies demonstrate only a limited degree of fibrovascular ingrowth. The aim of this study was to assess the effectiveness of both laser perforations and topically applied VEGF as methods of encouraging fibrovascular ingrowth. Treatment of Permacol with the diamond CO(2) laser significantly increased the porosity of the material as assessed by seescan image analysis. Fibrovascular ingrowth as assessed in the Sprague-dawley rat model was found to be limited to the pores themselves and not the surrounding native matrix. Pre-soaking of laser treated Permacol in vascular endothelial growth factor (VEGF) did not further increase fibrovascular ingrowth. Increasing the porosity of Permacol may allow its use as a dermal replacement in the support of an overlying skin graft or keratinocyte sheet; however using the laser may not be the optimal method of achieving this aim.

Animals↗
PubMed2004

Hyperglycaemic crises and lactic acidosis in diabetes mellitus.

Diabetic ketoacidosis, hyperglycaemic hyperosmolar state, and lactic acidosis represent three of the most serious acute complications of diabetes. There have been some advances in our understanding of the pathogenesis of these conditions over the last three decades, together with more uniform agreement on their treatment and innovations in technology. Accordingly their incidence, morbidity, and mortality are decreasing, but at rates that fall short of our aspirations. Hyperglycaemic crises in particular remain an important cause of morbidity and mortality in diabetic populations around the world. In this article, understanding of these conditions and advances in their management, and the available guidelines for their treatment, are reviewed. As far as is possible, the recommendations are based on clear published evidence; failing that, what is considered to be a common sense synthesis of consensus guidelines and recommendations is provided.

Acidosis, Lactic↗
PubMed2004

Long-term outcomes in patients with prostate cancer managed with intermittent androgen suppression.

OBJECTIVES: To assess the long-term outcomes of patients with prostate cancer managed with intermittent androgen suppression (IAS) following their enrollment in an open, non-randomised feasibility study initiated 10 years ago. PATIENTS AND METHODS: Patients with prostate cancer who developed marked side effects following androgen deprivation were considered for entry into the study. All patients were required to have been managed with androgen deprivation for a minimum of 9 months and to have achieved PSA remissions to levels <4 ng/ml or falls to greater than 90% of pre-treatment levels. Patients remained off treatment until PSA values rose to >20 ng/ml or individuals became symptomatic--at which stage a 9-month cycle of androgen suppression was repeated. Such on-off cycling continued until hormone-resistant disease developed and patients proceeded (off trial) to second-line therapies. RESULTS: 75 patients were recruited to the study following an initial referral with treatment-related side effects specifically associated with androgen deprivation. 86% of these remain alive at a median of 134 months (11 years) since initial histological diagnosis. Survival times and times to hormone resistance (from first cycle hormone deprivation) have also been calculated. Overall there is a median survival time of 95 months (8 years) from initial (first-cycle) androgen deprivation in those presenting with localised or locally advanced disease and a median survival time of 87 months (7 years) for those presenting with metastatic disease. There exists a median of 83 months to hormone resistance in the localised and locally advanced group and a median of 50 months in those presenting with metastatic disease. We have calculated a 100% 5-year actuarial survival rate for those presenting with localised or locally advanced disease (from time of first cycle hormone ablation) and a 70% 5-year actuarial survival rate for those presenting with metastatic. CONCLUSIONS: Long-term outcome figures and actuarial survival rates presented here provide further support for a pulsed or intermittent approach to androgen ablation in patients with prostate cancer. In addition, they serve as valuable extended outcome data for patients managed in this way. Likewise, data presented here suggests that apparent survival advantages appear related, at least in part, to a delay in the onset of androgen resistance and that such a management approach is both safe and effective in those presenting with both metastatic disease as well as those with more localised pathology.

Androgen Antagonists↗
PubMed2004

Diurnal changes in hypothalamic neuropeptide and SOCS-3 expression: effects of lactation and relationship with serum leptin and food intake.

Rats normally eat about 85% of their food at night. Lactation increases food intake 3- to 4-fold, but the diurnal pattern of food intake persists. The mechanisms responsible for the diurnal and lactation-induced changes in food intake are still unresolved, hence we have further investigated the possible roles of serum leptin and hypothalamic expression of neuropeptide Y (NPY), agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in rats. Suppressor of cytokine signalling-3 (SOCS-3) acts as a feedback inhibitor of leptin signalling in the hypothalamus, hence changes in expression of SOCS-3 were also investigated. Changes in expression of NPY, AgRP or POMC alone could not account for the diurnal changes in intake and their alteration by lactation. However, there were increased AgRP mRNA:POMC mRNA ratios at night and also during lactation, which were very similar to estimated changes in food intake. Such changes in expression may result in dominance of the orexigenic AgRP peptide over the appetite-suppressing POMC-derived peptides, and so could contribute to the hyperphagia in these states. Diurnal and lactation-related changes in the AgRP mRNA:POMC mRNA ratio and food intake are not due to changes in leptin alone. However, hypoleptinaemia, possibly through increased expression of NPY, may contribute to the hyperphagia of lactation. In the dark, expression of SOCS-3 was decreased in non-lactating rats; lactation decreased SOCS-3 expression in both light and dark phases. However, such changes are likely to enhance the ability of leptin-responsive neurones to transmit the leptin signal, and so are unlikely to contribute to either the nocturnal increase in appetite or the hyperphagia of lactation.

Agouti-Related Protein↗
PubMed2003

Prefabricated skin flaps in a rat model based on a dermal replacement matrix Permacol.

The reconstruction of three-dimensional structures is one of the most challenging problems in plastic surgery. While shaped frameworks incorporated within soft tissue envelopes often lose their fine detail, the integration of a blood supply to a stable biomaterial scaffold allows skin graft cover and emphasis of fine detail. The aim of this study was to evaluate whether a porcine derived isocyanate crosslinked collagen tissue matrix (Permacol) could be vascularised from an isolated vascular pedicle and subsequently sustain an overlying skin graft as a pedicled prefabricated flap. A vascular induction technique was employed using the epigastric pedicles in Sprague-Dawley rats to vascularise 2 x 2 cm(2) pieces of Permacol of standard 0.75 and 1.5 mm thickness Permacol and laser treated Permacol of 0.4 and 0.75 mm thickness. Flaps were able to support overlying skin grafts as early as 2 weeks following vessel implantation and laser treated Permacol had an increased vascularity compared to standard Permacol with no evidence of degradation. The study showed that Permacol could be a useful matrix for use in tissue engineered flaps.

Animals↗
PubMed2003

Randomised crossover trial to assess the tolerability of LHRH analogue administration.

Luteinising hormone releasing hormone (LHRH) analogues are routinely used in the treatment of patients with advanced prostate cancer. This randomised crossover trial was conducted to compare patient comfort and tolerability between two commonly used LHRH analogues: goserelin acetate and leuprorelin acetate. A total of 50 patients were randomised into two groups, each receiving 6-monthly injections of leuprorelin acetate (a liquid presentation) and goserelin acetate (a depot pellet) and crossing over between treatments. Patients completed a simple visual analogue score for the discomfort felt from the injections. An analysis of variance model was used, and the results found that patients do tolerate leuprorelin acetate (0.589) better than goserelin acetate (1.343) (P < 0.001, CI = 95%).

Aged↗
PubMed2003

The rigid nasendoscope as a tool for difficult tracheal intubation: a manikin study.

We examined the use of the 30 degrees rigid nasendoscope in aiding difficult tracheal intubations. A Cormack and Lehane grade 4 difficult intubation (no view of glottis or epiglottis) was set up on a manikin. After 10 s of tuition, 40 anaesthetists attempted to pass a standard gum elastic bougie between the cords, with and without the nasendoscope, in randomised order. A bougie curved to an 'optimal curve' was also tested. Using the standard bougie 13/40 (33%) passed the bougie between the cords without the nasendoscope, compared with 31/40 (78%) when using the nasendoscope (p < 0.001). The 'optimal curve' bougie resulted in 29/40 (73%) and 39/40 (98%) success rates without and with the nasendoscope, respectively (p = 0.004). The nasendoscope is a simple and easy to use tool in grade 4 intubation, and results are improved further by the use of an 'optimal curve' bougie.

Attitude of Health Personnel↗
PubMed2003

Altered arousal response in infants exposed to cigarette smoke.

AIMS: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. METHODS: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8-12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10-12 hours using complex sleep polysomnography. RESULTS: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. CONCLUSION: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk of SIDS.

Adult↗
PubMed2003

From trench fever to endocarditis.

The case of a 44 year old woman with infective endocarditis due to Bartonella quintana, an organism long recognised to cause a condition known as trench fever, is reported. This case illustrates the lengthy differential diagnosis of "culture negative" endocarditis. In addition the presence of serological cross reactivity of Bartonella spp and Chlamydia spp demonstrates the potential for misdiagnosis in these circumstances.

Adult↗
PubMed2003

Regulation of serum leptin and its role in the hyperphagia of lactation in the rat.

The factors regulating serum leptin concentration and its relationship to the hyperphagia of lactation have been investigated in rats. Lactation results in hypoleptinaemia and loss, or at least marked attenuation, of the nocturnal rise in serum leptin. Litter removal resulted in a fall in food intake and restoration of the nocturnal rise in serum leptin. Returning the litter to the mother after a 48-h absence increased food intake and began to reinitiate milk production, but the nocturnal serum leptin levels were still increased at 48 h after litter restoration. Adjusting litter size to four, eight, ten or fourteen pups at parturition resulted in different rates of litter growth and food intake during the subsequent lactation, but had no effect on the degree of hypoleptinaemia. Reducing litter size from ten to four pups at mid-lactation resulted in a transient increase in both serum leptin and pup growth rate, while food intake fell to a level found in rats suckling four pups throughout lactation. Reducing milk production by injection of bromocriptine increased serum leptin, but did not restore the nocturnal rise in serum leptin; food intake decreased, but remained much higher than in non-lactating rats. Feeding a varied, high-energy diet resulted in a decrease in the weight of food ingested, but no change in calorie intake, and had no effect on the hypoleptinaemia. These studies suggested that the hypoleptinaemia of lactating rats is due to negative energy balance, but the loss of the nocturnal rise in serum leptin is due to the suckling stimulus. The negative energy balance of lactation does not appear to be caused by a physical constraint on food intake. While the hypoleptinaemia should facilitate the hyperphagia of lactation, other orexigenic signals must also be involved.

Animals↗
PubMed2003

Lactation modulates diurnal expression profiles of specific leptin receptor isoforms in the rat hypothalamus.

We investigated the effects of lactation on diurnal changes in serum leptin and hypothalamic expression of the leptin receptor isoforms, Ob-Ra, -Rb, -Rc, -Re and -Rf in rats. In non-lactating rats, serum leptin concentration was increased at night while hypothalamic mRNA levels of Ob-Rb, -Rc and -Re decreased; by contrast, expression of Ob-Ra and Ob-Rf was unchanged at night. There were significant negative correlations between serum leptin and mRNA expression of Ob-Rb (P<0.001) and Ob-Re (P<0.05), which were independent of time of day. In lactating rats, the nocturnal rise in serum leptin was attenuated. Daytime hypothalamic Ob-Rb mRNA levels were significantly lower than in non-lactating controls, and the normal nocturnal decreases in expression of Ob-Rb, -Rc and -Re were lost. The relationship between serum leptin and Ob-Re expression was not changed by lactation. Lactation had no effect on the expression of Ob-Ra mRNA in the hypothalamus. Decreased daytime Ob-Rb expression could lead to reduced hypothalamic sensitivity to leptin, and thus contribute to increased daytime appetite in lactating rats. Moreover, maintaining high levels of Ob-Re expression could, by increasing hypothalamic leptin-binding protein concentration and reducing local leptin bioavailability, further accentuate hyperphagia. Thus, selective changes in expression of specific isoforms of the leptin receptor may contribute to the hyperphagia of lactation in rats.

Animals↗
PubMed2002

Expression of uncoupling proteins-1, -2 and -3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor.

The abnormalities of lipid metabolism observed in cancer cachexia may be induced by a lipid-mobilizing factor produced by adenocarcinomas. The specific molecules and metabolic pathways that mediate the actions of lipid-mobilizing factor are not known. The mitochondrial uncoupling proteins-1, -2 and -3 are suggested to play essential roles in energy dissipation and disposal of excess lipid. Here, we studied the effects of lipid-mobilizing factor on the expression of uncoupling proteins-1, -2 and -3 in normal mice. Lipid-mobilizing factor isolated from the urine of cancer patients was injected intravenously into mice over a 52-h period, while vehicle was similarly given to controls. Lipid-mobilizing factor caused significant reductions in body weight (-10%, P=0.03) and fat mass (-20%, P<0.01) accompanied by a marked decrease in plasma leptin (-59%, P<0.01) and heavy lipid deposition in the liver. In brown adipose tissue, uncoupling protein-1 mRNA levels were elevated in lipid-mobilizing factor-treated mice (+96%, P<0.01), as were uncoupling proteins-2 and -3 (+57% and +37%, both P<0.05). Lipid-mobilizing factor increased uncoupling protein-2 mRNA in both skeletal muscle (+146%, P<0.05) and liver (+142%, P=0.03). The protein levels of uncoupling protein-1 in brown adipose tissue and uncoupling protein-2 in liver were also increased with lipid-mobilizing factor administration (+49% and +67%, both P=0.02). Upregulation by lipid-mobilizing factor of uncoupling proteins-1, -2 and -3 in brown adipose tissue, and of uncoupling protein-2 in skeletal muscle and liver, suggests that these uncoupling proteins may serve to utilize excess lipid mobilized during fat catabolism in cancer cachexia.

Adenocarcinoma↗
PubMed2002

Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans.

The mitochondrial uncoupling proteins-2 and -3 are putative mediators of thermogenesis and energy expenditure. We measured the mRNA levels of uncoupling proteins-2 and -3 in skeletal muscle from 12 gastrointestinal adenocarcinoma patients, of whom six had stable weight and six had lost 2-18 kg, and from six healthy controls undergoing elective surgery. Uncoupling proteins-3 mRNA levels were significantly higher in the muscle of the cancer patients with weight loss (2.2 +/- 0.47 arbitrary units) compared both with controls (0.39 +/- 0.20) and with cancer patients who had not lost weight (0.47 +/- 0.23; P<0.02). Uncoupling proteins-2 mRNA levels did not differ significantly between groups. Elevations in muscle uncoupling proteins-3 activity may enhance energy expenditure and this in turn could contribute to tissue catabolism.

Adenocarcinoma↗