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Biomedical subjects

S Collins

Publications and source records attributed to S Collins.

At least 37 records · Page 2Linked to original sources

Factors predisposing to suspected offending by adults with self-reported learning disabilities.

BACKGROUND: This study investigated factors contributing to suspected offending behaviour by adults with a history of learning disabilities taken into custody at a city police station. METHODS: Adults charged with offences, and/or leaving custody, during a defined period, were identified as having a possible learning disability using a four-item questionnaire (Lyall et al. 1995 a). A comparison group, of similar age, sex and IQ, was identified from a database of young people with learning difficulties. Information was obtained on interview about each individual's medical, psychiatric, social and family histories and psychological assessments were undertaken. RESULTS: In contrast to the comparison group, those in the 'offending' group were more likely to have a history of the following: losing contact with their father, forensic contact in one or more family members, past homelessness, illicit drug use, experiencing an excess of recent life events, self-reported behavioural problems at school, truancy, childhood police contact and contact with probation services. All had histories of repeated offending. There was also an increased rate of drug/alcohol dependence. Only two subjects in the study group had a full-scale IQ below 70. CONCLUSIONS: These differences would suggest that the presence of childhood behavioural problems, offending behaviour by other family members, family separation and other social disruption and the development of drug and alcohol related problems are potentially the most important factors in trying to understand why one group engaged in criminal behaviour. The offending group had many characteristics in common with general offending populations.

Adult

Risk of subsequent primary cancers in patients with carcinoma of the Ampulla of Vater.

Data were collected on subsequent primary cancers occurring in 194 individuals diagnosed with ampullary carcinoma during 1979-92 in the north western region of England, UK. Four cancers were identified compared with 6.62 expected (relative risk 0.60), suggesting that individuals with ampullary carcinoma are not at increased risk of developing subsequent primary cancers.

Adult

Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.

A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.

Adipose Tissue

RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient beta-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice.

OBJECTIVE: To investigate the role of hypercorticism in the development of compromised beta-adrenergic signalling in adipocytes of mature C57BL/6J-ob/ob mice. DESIGN AND EXPERIMENTAL UNITS: Mature male ob/ob mice and their lean littermates were treated with vehicle or the specific glucocorticoid receptor (GR) antagonist, RU-486 (30 mg/kg bw/d) for 21 d. MEASUREMENTS: Blood glucose, serum insulin, adipocyte Glut-4 expression, adipocyte Gs alpha expression, adenylylcyclase activation by beta-adrenergic receptor (beta-AR) agonists in adipocyte membranes and mRNA levels for beta 1-, beta 2- and beta 3-adrenergic receptor subtypes in adipocytes. RESULTS: RU-486 reduced blood glucose levels in ob/ob mice to levels that were not different from lean mice. RU-486 also reduced serum insulin by approximately 50% in ob/ob mice, but failed to restore depressed Gs alpha or GLUT-4 expression in adipocytes of ob/ob mice. RU-486 produced a two-fold increase in beta 3-AR mRNA in ob/ob mice and a small but significant improvement in isoprenaline-mediated adenylylcyclase activation. CONCLUSIONS: The present results indicate that glucocorticoid antagonism ameliorates diabetic symptoms of the mature ob/ob mouse, but does not lessen their obesity or fully reverse deficient expression and function of components of the adipocyte beta-adrenergic signalling cascade.

Adenylyl Cyclases

What changes in the organisation of cancer services will improve the outcome for women with ovarian cancer?

OBJECTIVE: To examine the influence of operator specialty, volume of work and referral to an oncologist on the survival of women with ovarian cancer. DESIGN: Population-based retrospective cohort study, using hospital records and Cancer Registry data. SETTING: The North Western Region, UK. POPULATION: Six hundred and ninety-one women undergoing laparotomy for histologically confirmed ovarian malignancy during 1991 to 1992. METHODS: Univariate and multivariate survival analyses. MAIN OUTCOME MEASURES: Univariate survival estimates. Relative risks, derived from Cox's proportional hazards model, describing the effect on survival of surgeons vs gynaecologists as baseline, high volume vs low volume operators and referral vs nonreferral to an oncologist. RESULTS: After adjusting for woman and disease-related prognostic factors, operation by a surgeon was shown to have an adverse impact on survival (RR = 1.58, 95% CI 1.19 to 2.10). Regardless of how a high volume operator was defined (in terms of the number of laparotomies performed), no survival advantage over low volume operators could be demonstrated. Women referred to an oncologist had significantly better survival than women not referred (RR = 0.54, 95% CI 0.43 to 0.68). CONCLUSIONS: All women undergoing surgery for ovarian cancer should have access to a gynaecological opinion and postoperatively should be referred for a nonsurgical oncological opinion.

Adolescent

Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice.

Fat intake has long been associated with the development of obesity. The studies described herein show that fat adversely affects adipocyte adrenergic receptor (AR) expression and function. As beta 3AR agonists have been shown to acutely reduce adipose tissue mass and improve thermogenesis in genetically obese rodents, we examined whether chronic supplementation of a high fat diet with a highly selective beta 3AR agonist, CL316,243 could prevent diet-induced obesity, and whether the effect could be sustained over prolonged treatment. C57BL/6J and A/J mice were weaned onto one of three diets: low fat (10.5% calories from fat), high fat (58% calories from fat), or high fat supplemented with 0.001% CL316,243. B/6J mice gained more weight on the high fat diet than A/J mice (at 16 weeks: B/6J, 36.6 +/- 1.4 g; A/J, 32.9 +/- 0.8 g; P < 0.002; n = 10), whereas weights on the low fat diets were similar (B/6J, 29.5 +/- 0.5 g; A/J, 28.8 +/- 0.6 g; P > 0.05; n = 10). CL316,243 prevented the development of diet-induced obesity in A/J animals, but not in B/6J animals. A/J mice weighed 26.0 +/- 0.5 g at 16 weeks, whereas B/6J animals on the same diet weighed 34.1 +/- 0.8 g (P < 0.00001; n = 10), but food intake was not different between the strains throughout the study. beta-Adrenergic stimulation of adenylyl cyclase in obese B/6J mice was decreased by more than 75% in white adipose tissue and by more than 90% in brown adipose tissue (BAT). In contrast, in fat-fed A/J mice, beta-agonist-stimulated adenylyl cyclase was decreased in white adipose tissue by about 10%, whereas the activity in interscapular BAT was decreased by 50%, indicating significant retention of beta AR-stimulated activity in A/J mice compared to B/6J mice. High fat feeding was associated with decreased expression of beta 3AR and beta 1AR in white adipose tissue of both strains. However, chronic CL316,243 treatment prevented both the obesity and the decline in beta 3AR and beta 1AR messenger RNA levels in all adipose depots from A/J mice, but not B/6J mice. As CL316,243-treated A/J mice, but not B/6J mice, also showed marked uncoupling protein expression in white adipose depots, the ability of chronic CL316,243 treatment to prevent diet-induced obesity is dependent upon the elaboration of functional BAT in these regions.

Adipocytes

Low plasma leptin in response to dietary fat in diabetes- and obesity-prone mice.

Despite the fact that mutations resulting in the absence of leptin or its receptor have been associated with severe obesity and diabetes, such mutations do not appear to be responsible for most human obesity. Indeed, diet-induced obesity in animals and humans has been characterized by hyperleptinemia. This has been interpreted as evidence for leptin resistance. However, no careful longitudinal studies evaluating the role of leptin in the development of obesity exist. We report a series of studies in A/J and C57BL/6J (B/6) mice that demonstrate a direct relationship between the ability to increase plasma leptin levels in response to a high-fat diet and resistance to the subsequent development of obesity and diabetes. While leptin levels are similar in lean, low-fat-fed A/J and B/6 mice, the effects of a high-fat diet on plasma leptin differ dramatically between the two strains. After 4 weeks of high-fat feeding, leptin levels in A/J mice increased 10-fold, and this elevated level was maintained independent of weight gain throughout a 14-week feeding period. However, in B/6 mice, leptin levels remained at least twofold lower and only rose very gradually along with a significant increase in adiposity, hyperglycemia, and hyperinsulinemia. These differences in the response of leptin to diet are independent of food intake and plasma insulin levels during the 1st month of feeding. Further, we demonstrated that leptin administration did not influence the expression of the novel uncoupling protein UCP2, which also responds to dietary fat. From these results, we suggest that the response of leptin to fat feeding may be an important predictor of the development of subsequent obesity.

Animals

Renal cryotherapy in a sheep model; a feasibility study.

PURPOSE: This study was designed to evaluate the safety and efficacy of renal cryotherapy as a possible treatment of renal malignancy with preservation of renal parenchyma. MATERIALS AND METHODS: Ten Merino sheep were anaesthetised and the right kidney was exposed through a retro-peritoneal approach. A 5 mm. cryotherapy probe (LCS 3000 Cryotec UK) was inserted into the lower pole of the kidney and freezing was undertaken to form an iceball 5 cm. in diameter. RESULTS: There was no mortality and no complications were observed. A transient rise in creatinine was observed post-operatively. The sheep were euthenased at 4 weeks and at necropsy macroscopic examination revealed a contracted, fibrotic wedge shaped lesion of 3 cm in diameter. Histological examination of the "cryolesion" revealed a central area of coagulative necrosis and a 5 mm rim of partial necrosis with preservation of renal tubules. CONCLUSION: We conclude that renal cryotherapy is safe and can achieve effective renal necrosis in the sheep model.

Animals

Perspectives on AAC systems by the users and by their communication partners.

The study examined the perspectives of augmentative and alternative communication (AAC) users and their 'formal' and 'informal' communication partners in relation to two areas of relevance to AAC: firstly, communication strategies, and secondly, advantages and disadvantages of AAC systems. With respect to communication strategies, it was found that formal communication partners thought that more vocabulary for communicating social purposes was actually available to AAC users and they were less aware of daily routines within day and residential environments. With respect to advantages and disadvantages, three main areas of concern emerged: the effect of the AAC system on the users' communication; features of AAC systems; and the effect of AAC on the users' quality of life. Both high- and low-technology AAC systems were seen as having advantages and disadvantages. This study demonstrates the important contribution to be made by AAC users in the provision of a new set of priorities based on their user experiences.

Adolescent

Adequacy of cervical cytology sampling with the Cervex brush and the Aylesbury spatula: a population based randomised controlled trial.

OBJECTIVE: To compare the adequacy of cervical cytology sampling with two sampling instruments commonly used in primary care-namely, the Aylesbury spatula and the Cervex brush. DESIGN: Pair matched, population based randomised controlled trial. SETTING: 86 general practices and family planning clinics in Greater Manchester. SUBJECTS: 15 882 cervical smears taken from women aged 20-64 years as part of the national cervical screening programme. INTERVENTIONS: Participating centres were allocated to sample with either the Cervex brush or the Aylesbury spatula. MAIN OUTCOME MEASURE: Inadequate smear rate. RESULTS: 5.4% and 5.5% (433/8086 and 426/7796) of smears taken with the Cervex brush and the Aylesbury spatula respectively were reported as inadequate (odds ratio 0.95; 95% confidence interval 0.74 to 1.22). CONCLUSION: The Cervex brush offers no advantage over the Aylesbury spatula in reducing inadequate smear rates in the primary care setting.

Adult

Using middle upper arm circumference to assess severe adult malnutrition during famine.

OBJECTIVES: To examine the use of middle upper arm circumference measurement (MUAC [cm]) and body mass index measurement (BMI [kg/m2]) in the screening of severely malnourished adults during famine. DESIGN: Nonrandomized cohort study, correlating measurements of MUAC and BMI. SETTING: The Concern Worldwide adult feeding center in the village of Ayod in south Sudan. The area has experienced several years of war, leading to severe famine during early 1993. PARTICIPANTS: A total of 98 adult inpatients belonging to the Nuer tribe. Criteria for entry into the study were prior admission to the feeding center and the ability to stand and have a BMI measured. MAIN OUTCOME MEASURES: A comparison of the ease of use of MUAC and BMI assessments, and a correlation of MUAC and BMI measurements. RESULTS: An MUAC measurement was easier to perform on severely malnourished adults than BMI assessment. For MUAC, the patient could be standing, sitting, or, in extreme cases, lying. For BMI, patients were required to stand. Measuring BMI requires a height board, weighing scales, and mathematical calculations; to measure MUAC, only a tape measure is required. A correlation between measurements of MUAC and BMI was demonstrated (r=0.88; 95% confidence interval, 0.82-0.92 P<.001). The proportions of the population and the actual individuals identified as malnourished by the 2 indicators were similar. CONCLUSIONS: The MUAC measurement reflects adult nutritional status as defined by BMI. During famine, MUAC may be better suited to screening admissions to adult feeding centers than BMI. Studies to assess the capacity of MUAC cutoffs to predict mortality in severe adult malnutrition are needed.

Adult

Iatrogenic and zoonotic Creutzfeldt-Jakob disease: the Australian perspective.

The transmissible brain diseases of humans and animals, the spongiform encephalopathies, continue to stimulate interest, and the announcement that exposure to "mad cow disease" (bovine spongiform encephalopathy [BSE]) is a possible explanation for more than 10 cases of a variant Creutzfeldt-Jakob disease in humans in the United Kingdom is a recent example. Cases of iatrogenic Creutzfeldt-Jakob disease (from previous use of human cadaveric tissues for pituitary hormone therapy and neurosurgical grafts) are still being identified, and the unique nosological status of this group of disorders-that they are both transmissible and inherited and that the only known component of their infectious agent is protein-alone makes these diseases remarkable.

Animals

Pharmacologic manipulation of ob expression in a dietary model of obesity.

Mutation of the obese (ob) gene results in severe hereditary obesity and diabetes in the C57BL/6J and related strains of mice. In this study we examined the expression of the ob gene in a dietary model in which moderate obesity develops in response to fat (58% of calories from fat) without mutation of the ob gene, and in four genetic models of obesity in mice: ob/ob, db/db, tubby, and fat. Several white and brown adipose depots were examined (epididymal, subcutaneous, perirenal, and interscapular). Northern blot analysis shows that levels of ob mRNA are increased in all adipose depots examined in every model of obesity. The average fold increases were 12.0 +/ 2.1 (ob/ob), 4.8 +/- 1.5 (db/db), 2.8 +/- 0.1 (tubby), 2.4 +/- 0.3 (fat), and 2.1 +/- 0.2 (high fat diet-induced A/J). Moreover, we found that the expression of the ob gene could be manipulated by pharmacologically blocking the development of diet-induced obesity. Supplementation of a high fat diet with a beta 3-adrenergic receptor agonist (CL316,243) prevented obesity, but not hyperphagia associated with high fat feeding (body weights of high fat-fed A/J mice = 34.0 +/- 1.0 g; high fat plus CL316,243-fed mice = 26.8 +/- 0.5 g; n = 10). CL316,243-treated, high fat-fed animals contained levels of ob mRNA in all adipose depots that were equal to or less than levels in low fat-fed mice (average levels in high fat plus CL316,243-fed mice relative to low fat-fed mice: 0.93 +/- 0.09). Inasmuch as fat cell size, but not number, was increased in a previous study in diet-induced obese A/J mice, these results indicate that expression of the ob gene serves as a sensor of fat cell hypertrophy, independent of any effects on food intake.

Adipose Tissue

Abnormalities of smooth eye and head movement control in Parkinson's disease.

The control of horizontal head and eye movements was examined in 13 nondemented patients with Parkinson's disease (PD) of mild to moderate severity. During pursuit of single-frequency sine waves, smooth component eye velocity was lower in the PD group at frequencies of 1.2 Hz and above; but the differences in overall eye displacement were even greater, indicating an impaired ability to generate catch-up saccades at high frequencies. A corresponding deficit in saccadic performance was observed during a high-frequency saccadic tracking task where predictive saccades of reduced gain and variable timing were generated. During pursuit of pseudo-random target motion with varying degrees of predictability, small differences in smooth component eye velocity were observed, but prediction was otherwise well preserved in the patient group. Vestibulo-ocular reflex (VOR) suppression was also normal during head-free pursuit. No major improvement in smooth pursuit gain could be attributed to drug treatment, based on a comparison of patient results before and after administration of levodopa.

Adult