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Biomedical subjects

P Illingworth

Publications and source records attributed to P Illingworth.

16 recordsLinked to original sources
PubMed2002

HOVIS -- The Hertfordshire/Oxfordshire Violent Incident Study.

Violence in psychiatric inpatient units is a major and growing problem. Research interest has primarily focussed on patient characteristics. The role of staff factors and the antecedents of violent incidents has been neglected, despite the fact that staff factors and behaviour may be more readily amenable to change than patient characteristics. The HOVIS study sought to obtain the views of a sample of mental health nurses in current clinical practice about staff-related factors, which they perceive to contribute to, or protect against, the occurrence of violent incidents. A total of 108 nurses working in psychiatric acute admission, intensive care and low secure units, in two NHS Trusts were interviewed using a specially designed semistructured interview schedule. These nurses identified a variety of behaviours, clinical skills, personal characteristics and interpersonal skills that they believe impact on the occurrence of violent incidents. These findings are discussed in relation to their possible training and managerial implications.

Adult↗
PubMed2002

Inhibin and activin secretion during murine preantral follicle culture and following HCG stimulation.

BACKGROUND: Isolation and culture to antral stage of mouse preantral follicles provides an ideal system for investigating the endocrinology of follicular development to maturity. METHODS: The release of inhibin A, inhibin B, pro-alphaC and activin A was measured at specific time-points throughout an in-vitro culture period of 8 days. At the end of culture, follicles were induced to ovulate in vitro by the addition of HCG and the resulting hormone secretion studied both at 20 h and at 6 h intervals. RESULTS: During the preovulatory culture period, the concentrations of inhibin A, B, pro-alphaC and activin A increased significantly. Compared with control, there was a significant decline at 24 h in the concentrations of inhibin A [P < 0.001; 216 +/- 47 versus 823 +/- 110 arbitrary mouse units (amu)/ml], inhibin B (P < 0.01; 131 +/- 23 versus 361 +/- 45 amu/ml) and pro-alphaC (P < 0.001; 14 +/- 5 versus 1198 +/- 212 pg/ml). In contrast, there was a significant increase in the concentration of activin A (P < 0.001; 1.32 +/- 0.04 versus 0.34 +/- 0.03 ng/ml). CONCLUSIONS: These data provide clear evidence of a profound change in the relative secretion rates of inhibin and activin relative to ovulation and suggest that the principal role of activin A may be at time of ovulation rather than during follicular development.

Activins↗
PubMed2001

In-vitro growth of murine pre-antral follicles after isolation from cryopreserved ovarian tissue.

The low temperature storage of ovarian tissue allows patients at risk of premature menopause to preserve their fecundity. One strategy for harvesting mature oocytes may be to isolate small follicles from the stroma for in-vitro culture. The aim of this study was to assess the survival and growth of murine follicles during in-vitro culture after isolation from tissue frozen-thawed in various cryoprotective agents. The effect of different seeding and thawing temperatures was also investigated. Pre-antral follicles 100--135 microm in diameter were isolated from fresh and frozen-thawed tissue and cultured in vitro for 8 days. In the fresh control group 79 +/- 3% of follicles survived in-vitro culture and grew to antral stages. Fewer follicles survived after isolation from tissue cryopreserved in dimethyl sulphoxide (43 +/- 5%) or propylene glycol (24 +/- 2%) and none survived freeze-thawing in glycerol. Lowering the seeding temperature from -5 degrees to -7 degrees or -9 degrees C reduced follicle survival rates from 49 +/- 4% to 26 +/- 1% and 28 +/- 3% respectively. If thawing was carried out at 27 degrees C follicle survival rate was higher (38 +/- 7%) than at 37 degrees C (26 +/- 2%) or 47 degrees C (20 +/- 6%). Follicles surviving 8 days of in-vitro culture were stimulated with human chorionic gonadotrophin. The number of mature oocytes released did not differ between any experimental group. The results indicate that follicles isolated from frozen-thawed tissue can be grown to antral sizes and produce mature oocytes. The in-vitro culture system also proved a sensitive method for testing variations in the freeze-thaw protocol.

Animals↗
PubMed2001

A novel transgenic model to characterize the specific effects of follicle-stimulating hormone on gonadal physiology in the absence of luteinizing hormone actions.

Gonadal function is wholly reliant on the two pituitary-derived gonadotropins, FSH and LH. Identifying the specific effects of FSH has been difficult because of the intimate relationship between LH and FSH action and inherent limitations of classic research paradigms. We describe a novel transgenic model to characterize the definitive actions of FSH alone, distinct from LH effects, created by combining transgenic FSH expression with the gonadotropin-deficient background of the hypogonadal (hpg) mouse. A tandem transgene construct encoding each alpha- and beta-subunit of human FSH, under the rat insulin II promoter, expressed biologically active heterodimers at serum levels, by immunoassay, equivalent to circulating FSH concentrations in fertile humans (0.1-25 IU/liter). Transgenic mice were crossed into the hpg mouse genotype to obtain LH-deficient animals secreting FSH alone. Testis weights of adult FSHxhpg mice were increased up to 5-fold, relative to nontransgenic hpg controls (P < 0.001). However, only transgenic males with serum FSH levels more than 1 IU/liter showed testis weights increased relative to hpg controls, indicating a physiological FSH threshold for the testicular response. Histology of enlarged FSHxhpg testes revealed round spermatids and sparse numbers of elongated spermatids, demonstrating that the testosterone-independent FSH response targeting the Sertoli cell can facilitate completion of meiosis and minimal initiation, but not completion, of spermiogenesis. Transgenic FSH also induced inhibin B secretion in FSHxhpg mice, but showed a distinct sexual dimorphism with only females exhibiting a strong FSH dose-dependent increase in serum inhibin B levels (r(2) = 0.84). In addition, ovaries of FSHxhpg females were enlarged up to 10-fold (P < 0.001), characterized by increased follicular recruitment and development to type 7 antral follicles. Thus, these findings show that the transgenic FSHxhpg mouse provides a unique model for detailed investigations of the definitive in vivo actions of FSH alone.

Animals↗
PubMed2000

Bluffing, puffing and spinning in managed-care organizations.

I argue that because bluffing, puffing, and spinning are features of corporate life, they are likely to characterize the doctor-patient relationship in managed care medicine. I show that managed-care organizations (MCOs) and the physicians who contract with them make liberal use of puffing and spinning. In this way, they create a context in which it is likely that patients will also use deceptive mechanisms. Unfortunately, patients risk their health when they deceive their doctors. Using the warranty theory of truth I argue that although bluffing may be ethical in business because all participants agree to it and business has not warranted truth-telling, it is not ethical in a medical context because physicians and MCOs have warranted truth-telling and the quality of medical care depends on it.

Deception↗
PubMed1999

Ectopic expression of protein kinase CbetaII, -delta, and -epsilon, but not -betaI or -zeta, provide for insulin stimulation of glucose uptake in NIH-3T3 cells.

Insulin regulates a diverse array of signaling pathways involved in the control of growth, differentiation, proliferation, and metabolism. Insulin increases in glucose uptake via a protein kinase C-dependent pathway in target tissues such as fat and muscle are well documented. Insulin-regulated events, however, occur in all cells. The utilization of glucose as a preferred energy source is a ubiquitous event in eukaryotic cells. In NIH-3T3 fibroblasts, insulin treatment increased levels of the cPKC and nPKC activator, diacylglycerol. Insulin-responsive 2-[(3)H]deoxyglucose uptake was stimulated in a dose-dependent manner. The overexpression of protein kinase C (PKC)betaI, -betaII, -delta, -epsilon, and -zeta was used to investigate the specificity of PKC isozymes for insulin-sensitive glucose uptake. The stable overexpression of PKCbetaII, -delta, and -epsilon resulted in increases in insulin-stimulated 2-[(3)H]deoxyglucose uptake compared to vector control cells, while basal 2-deoxyglucose uptake levels were not elevated. Overexpression of PKCbetaI and PKCzeta isozymes had no further effect on basal or insulin-stimulated 2-deoxyglucose uptake. The PKC-specific inhibitor, CGP41251, blocked insulin effects on 2-deoxyglucose uptake but not its effects on tyrosine phosphorylation of cellular substrates. Insulin-stimulated 3-O-methylglucose uptake was also greater in cells overexpressing PKCbetaII, -delta, and -epsilon, compared to control cells. The increased responsiveness was not accompanied by conversion of 3T3 cells to the adipocyte phenotype or the increased expression of insulin receptors or glucose transporters (GLUT1-type). Insulin-stimulated recruitment of GLUT1 to plasma membranes of cells overexpressing PKCbetaII, -delta, and -epsilon, was greater than that in control cells. The data suggest that more than one PKC isozyme is involved in insulin signaling pathways in fibroblasts, resulting in increased GLUT1 transporter recruitment to cell membranes.

3-O-Methylglucose↗
PubMed1994

Progesterone control of interleukin-8 production in endometrium and chorio-decidual cells underlines the role of the neutrophil in menstruation and parturition.

Interleukin-8 (IL-8) attracts neutrophils into tissues and causes them to degranulate. Both menstruation and parturition involve neutrophil migration into uterine tissues and therefore IL-8 is a likely mediator of the tissue re-arrangements that accompany these events. We have examined the ability of endometrium explants and chorion cells in culture to synthesize and release IL-8 and the ability of progesterone, a synthetic progestin [medroxyprogesterone acetate (MPA)] and dexamethasone to inhibit this production. In endometrium, the stage of the menstrual cycle did not affect IL-8 production but a 10(-6) M concentration of progesterone or dexamethasone significantly reduced the concentration of IL-8 in medium after 24 h. After a further 24 h with lipopolysaccharide (LPS) stimulation, only MPA and dexamethasone inhibited production significantly. In chorion cells, IL-8 production was significantly decreased by both MPA and dexamethasone in the LPS stimulated cells but the reduction in the first 24 h was not significant. The IL-8 produced in uterine tissues might act synergistically with prostaglandin E (PGE), a likely site for this interaction being blood vessels where PGE production is also repressed by progesterone. Such a cooperative action would maintain low leukocyte entry into uterine tissues in the presence of progesterone and falling steroid levels would induce leukocyte immigration and activation with consequent tissue destruction. Such steroid-dependent interactions are important in our understanding of the mechanisms of menstruation and parturition and could allow new approaches to the treatment of uterine pathology.

Cells, Cultured↗
PubMed1988

Heterogeneity of noradrenergic thermic responses in obese and lean humans.

The thermic response to noradrenaline infusion was measured by indirect calorimetry in 40 newly referred obese subjects and 19 lean controls. A marked variation in response was found, more so in the obese than in the lean. In the lean group the lowest noradrenergic thermic response was 12.8 kJ but in the obese group 26 per cent had a thermic response less than this. When the thermic response to noradrenaline is expressed as a percentage of the resting metabolic rate the response was significantly (P less than 0.002) lower in the obese, 8.5 (s.d. 6.0) per cent compared with 13.8 (s.d. 5.1) per cent in the lean. The lowest value in the lean group was 7.8 and 42 per cent of the obese group had lower values. The thermic responses in the obese group did not correlate with glucose:insulin ratios measured both fasting and in response to oral glucose, or with the cumulative rises of either free fatty acids or glycerol during the noradrenaline infusion. Hence the majority of obese subjects have a 'normal' response to infused noradrenaline, but there is a subgroup who do have a blunted response. This may explain to some extent the conflicting reports in the literature regarding the presence of otherwise of a thermic defect in obesity.

Adult↗
PubMed1986

Effect of optimal glycaemic control with continuous subcutaneous insulin infusion on energy expenditure in type I diabetes mellitus.

To assess the role of insulin in the control of body weight energy expenditure was measured by indirect calorimetry in eight patients of normal weight with type I diabetes initially while poorly controlled during conventional insulin treatment and later during optimal glycaemic control achieved by using the continuous subcutaneous insulin infusion pump. Their response to seven days of fat supplementation was also assessed and the results compared with those in eight non-diabetic subjects. After a mean of 5.3 months of continuous subcutaneous insulin infusion the diabetic subjects had gained on average 3.5 kg. In the poorly controlled diabetic state the resting metabolic rate was raised but decreased by a mean of 374 kJ (90 kcal) per 24 hours with optimal glycaemic control. The thermic response to infused noradrenaline was reduced by 59% in the diabetic subjects, was not improved by continuous subcutaneous insulin infusion, but was improved when three of the subjects were given metformin in addition. The diabetic subjects had no abnormality in the thermic response to a meal while taking their usual diabetic diet. During fat supplementation, however, this thermic response was reduced when glycaemic control was poor but not when control was precise. Fat supplementation did not alter the resting metabolic rate or the reduced noradrenergic thermic response in the diabetic subjects. These findings suggest that precise glycaemic control could produce weight gain if energy intake remained unaltered, for diabetic subjects do not compensate for the decrease in metabolic rate by an increase in noradrenergic and dietary thermic responses. Also precise glycaemic control using continuous subcutaneous insulin infusion does not correct all the metabolic abnormalities of diabetes mellitus.

Adult↗
PubMed1985

The characterization and energetic potential of brown adipose tissue in man.

In adult man, brown fat can be detected in perinephric fat depots by visual inspection, electron microscopy and nucleotide binding to the tissue-specific uncoupling protein. The 32 kDa uncoupling protein is functionally active, showing a nucleotide-sensitive conductance to protons and an uncoupling response to fatty acids. The amount of uncoupling protein in human mitochondria is equivalent to that in a partially cold-adapted guinea pig, indicating some potential for thermogenesis. Respiratory capacity measurements indicate that the total perinephric fat in adult man can only account for one-fivehundredth of the whole-body response to infused noradrenaline. Thus, although brown fat has been found to be quantitatively important in animal studies, considerable caution must be exercised in extrapolating its significance to adult man.

Adipose Tissue, Brown↗
PubMedDate not supplied

Electrically mediated drug delivery for treating subcutaneous and orthotopic pancreatic adenocarcinoma in a hamster model.

BACKGROUND: Current therapies for pancreatic adenocarcinoma only benefit a fraction of those diagnosed with this disease. New strategies for improving treatment are clearly needed. This study investigated the use of electrically mediated drug delivery for the treatment of pancreatic adenocarcinoma in a hamster model. MATERIALS AND METHODS: Hamster PC-1 pancreatic adenocarcinoma cells and Golden Syrian hamsters were used as a model. RESULTS: In vitro testing indicated that bleomycin was more effective than Cisplatin and Doxorubicin when delivered using pulsed electric fields. Treatment of subcutaneous tumors with bleomycin and electric fields resulted in a 100 percent complete response rate. No effect was observed when either drug or pulses were used alone. Treatment of tumors induced in the gland resulted in a 25 percent complete response rate. CONCLUSIONS: Electrochemotherapy was highly effective for subcutaneous tumors. There was also a significant antitumor effect for the more complex and clinically relevant intraoperative treatment of tumors in the pancreas.

Adenocarcinoma↗
PubMedDate not supplied

Return to sender.

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Cost Control↗
PubMedDate not supplied

Looking after Gemma.

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Chromosomes, Human, Pair 18↗