Biomedical subjects

K Hunt

Publications and source records attributed to K Hunt.

At least 55 records · Page 3Linked to original sources

PubMed1997

Characterization of pigs transgenic for human decay-accelerating factor.

BACKGROUND: To prevent the central role played by complement activation in the hyperacute rejection of pig organs transplanted into primates, pigs transgenic for human decay-accelerating factor (HDAF) have recently been produced. The data presented here extend previous immunohistochemical findings by documenting the immunological characterization and the levels of expression of HDAF in these transgenic pigs. METHODS: Animals from 30 independently derived lines were included in this study. HDAF expression was characterized by immunoprecipitation and epitope mapping. Quantitative analysis was performed by radiometric assays followed by Scatchard analysis and by double-determinant radioimmunoassay. Deposition of iC3b on porcine aortic endothelial cells was determined by radioimmunoassay. DNA slot-blot analysis and densitometric scanning were used to evaluate HDAF transgene copy number. RESULTS: The integrity of HDAF expressed by these transgenic pigs could be demonstrated. HDAF was present in 72% of the organs analyzed, although considerable variation in expression occurred, both between animals and within the same pig. High levels of HDAF on porcine aortic endothelial cells resulted in iC3b deposition at levels as low as that detected on human endothelial cells. Twenty-six organs expressed levels of HDAF greater than those observed in the equivalent human tissue. HDAF expression did not correlate with the number of copies of the transgene incorporated into the porcine genome. CONCLUSIONS: Transgenic pigs, which express levels of functional HDAF even greater than those observed in humans, have successfully been produced. Pigs transgenic for human complement inhibiting molecules could represent a source of organs for future clinical xenotransplantation.

Animals↗

PubMed1997

NHS reforms. Counting the costs.

Localism predominates in purchaser-provider relationships, with markets strictly limited in practice. Block contracting predominates, largely to enable purchasers to bring pressure to bear on providers' costs and outputs. The administrative costs of operating the purchaser-provider split have led to a clear growth in the overall administrative costs within the NHS. Locality commissioning may conflict with the need to reorganise clinical services.

Contract Services↗

PubMed1997

Transduction of murine and human tumors using recombinant adenovirus vectors.

BACKGROUND: Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. METHODS: AdV vectors contained a reporter (Escherichia coli beta-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. RESULTS: All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI > 100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. CONCLUSIONS: E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels.

Adenoviridae↗

PubMed1997

Morbidity and Irish Catholic descent in Britain: an ethnic and religious minority 150 years on.

Ethnic and religious minorities often suffer disadvantages both in socio-economic status and in health. Data from the West of Scotland Twenty-07 study suggest some differences in morbidity between those descended from Irish Catholic migrants of the great emigration from 1840 onwards and others. Catholic religion of at least one parent or at birth is used here as a proxy measure to indicate Irish Catholic descent, on the basis of estimates of sensitivity and specificity in the local area. Higher proportions of "Catholics" are in manual social classes. Differences between "Catholics" and "non-Catholics" in one or more age cohorts are observed for the following aspects of health and physical development: general and physical health (self-assessed health, number of symptoms, accidents), psychological distress (depression, anxiety, number of psychosomatic symptoms), impairments and disabilities (sight, hearing, wearing dentures, disability), and physical measures (height, waist-to-hip ratio, lung function). Furthermore, for all aspects except hearing, wearing dentures and number of psychosomatic symptoms, significant differences remain after accounting for sex and social class. For each measure where a difference is observed, it is those respondents with a Catholic parent or who were born Catholic who experience poorer health or physical development. This suggests that those of Irish Catholic descent are at some disadvantage compared with the rest of the population, with respect to health as well as social class, 150 years after the start of the main migration.

Adolescent↗

PubMed1997

Psychological distress among British South Asians: the contribution of stressful situations and subcultural differences in the West of Scotland Twenty-07 Study.

BACKGROUND: This paper seeks to explain an excess of psychological distress previously found among groups of British South Asians (with ancestry from the Indian subcontinent) living in Glasgow, compared with the general population. The excess was found on a psychosomatic measure and a measure of self-assessed distress but not on a clinically validated measure (the General Health Questionnaire or GHQ). The paper investigates whether South Asians are subject to stressful situations to which the GHQ is less sensitive than the other two measures. METHODS: Random samples of 159 South Asians aged 30-40, mean age 35, and 319 from the general population, all aged 35, were interviewed in Glasgow, using the 12-item General Health Questionnaire (GHQ-12), a psychosomatic symptom scale (PSS) and a self-assessment of distress. Subcultural groupings were differentiated by South Asian origin, English fluency, religion, and gender. Stressful situations assessed were experience of assault, stress/dissatisfaction with work, overcrowding, low standard of living, absence of family and absence of confidants. RESULTS: The GHQ-12 was less sensitive to certain stressful situations than the other two measures. The PSS and/or self-assessed distress were more sensitive to low standard of living, self-rated stress in work around the house and possibly experience of assault. In a combined analysis, the relation between distress on the PSS or self-assessed measure and subcultural groupings became nonsignificant, while the relation between distress and key stressful situations remained significant. CONCLUSIONS: The greater distress of women, Muslims and limited English speakers is largely explained by the stressful situations they experience. The GHQ-12 under-estimates distress related to situations experienced particularly by ethnic minorities and by women.

Adult↗

PubMed1996

Gender differences in health: are things really as simple as they seem?

It is conventional wisdom in medical sociology and social epidemiology that in industrialized societies men die earlier than women, but that women have poorer health than men. A number of explanations for these differences have been postulated and tested (for example, different biological risks, acquired risks, reporting biases and experiences of health care). Using two recent British data sets we find that the pattern of sex differences in morbidity is more complicated than the conventional wisdom often suggests. The direction and magnitude of sex differences in health vary according to the particular symptom or condition in question and according to the phase of the life cycle. Female excess is only consistently found across the life span for psychological distress and is far less apparent, or reversed, for a number of physical symptoms and conditions. Detailed inspection of papers on gender differences published in the last decade reveals that our findings are not unique, but that a relatively undifferentiated model of consistent sex differences has nevertheless continued to predominate in the literature. We believe that the topic of gender differences in health warrants periodic re-examination.

Adolescent↗

PubMed1996

Irish descent, religion, and alcohol and tobacco use.

The West of Scotland has traditionally been a focus for Irish migration. Using data from two studies carried out in this region, one quantitative, the other qualitative, this paper shows little difference in drinking and smoking between Scots of Irish descent and other Scots. It does, however, show significant differences in these behaviours according to religious affiliation in adulthood. Rather than confirming the stereotype of Irish Catholics as heavy drinkers and smokers the present paper puts forward the hypothesis that drinkers and smokers are differentially retained in membership by different religious affiliations, and argues that this accounts for differences in reputation and in health-related behaviours.

Adolescent↗

PubMed1996

Accreditation at what cost?

Analyses the implications of the management of labour for an organization undertaking an accreditation exercise. Considers the King's Fund Organizational Audit (KFOA) accreditation scheme, which is concerned with process and facilities, and assesses the quality of the hospital environment in which the health care product is supplied. Concludes that, given the current enthusiasm for finding best practice in health care and the ever-increasing number of cost-effectiveness analyses of therapeutic interventions, it seems somewhat contradictory that interventions which cover the whole environment in which health care interventions are performed are not treated in the same way.

Accreditation↗

PubMed1996

Ergonomics: a case study in preventing repetitive motion injuries.

Dental Services Group has designed and implemented a system for its dental laboratories to mitigate cumulative trauma injuries, such as carpal tunnel syndrome and tendinitis. In the dental laboratory, these injuries result from repetitive motions such as waxing, sandblasting, grinding and polishing. This article describes purchasing guidelines for ergonomically designed laboratory equipment and offers resources for implementing workplace safety programs.

Cumulative Trauma Disorders↗

PubMed1994

The hexosamine biosynthetic pathway and glucose-induced down regulation of glucose transport in L6 myotubes.

Based on experiments in cultured adipocytes, it has been proposed that glucose-induced down regulation of glucose transport is mediated by the conversion of fructose-6-phosphate to glucosamine-6-phosphate via the first and rate-determining enzyme of the hexosamine biosynthetic pathway, glutamine: fructose-6-phosphate amidotransferase (glutamine hexosephosphate aminotransferase). Evidence for this assertion was: (a) L-glutamine, the provider group for the aminotransferase was essential; (b) two inhibitors of glutamine hexosephosphate aminotransferase, 6-diazo-5-oxonorleucine (L form) and azaserine, blocked glucose-induced down regulation of glucose transport; (c) azaserine inhibited the activity of the aminotransferase, (d) glucosamine, which enters the hexosamine pathway distal to this enzyme was 40-times more potent than glucose; and (e) azaserine was unable to block the effect of glucosamine. Since muscle is quantitatively much more important than adipose tissue for whole body glucose utilization, we sought to determine if the hexosamine pathway was involved in glucose-induced down regulation of glucose transport in L6 myotubes. Glucose was effective, both in the presence and absence of glutamine in the incubation media. Glucosamine was also effective but was as equipotent as glucose. Small amounts of glutamine hexosephosphate aminotransferase were present in the L6 myotubes and although the leucine derivative (20 microM) inhibited the enzyme, it did not impair glucose-induced down regulation of glucose transport. Total GLUT-1 levels were similar when the cells were incubated in the absence or presence of 5 mM glucose or glucosamine although glucosamine was associated with a marked increase in a lower molecular weight band. These results do not suggest that the hexosamine biosynthetic pathway is involved in glucose-induced down regulation of glucose transport in L6 myotubes. Thus, this phenomenon is regulated differently in muscle and fat.

Animals↗

PubMed1994

Emphysematous cholecystitis after ERCP.

Emphysematous cholecystitis is a rare variant of acute cholecystitis, most frequently seen in elderly, debilitated, or diabetic patients. This report documents the development of fulminant sepsis due to acalculous cholecystitis after endoscopic retrograde cholangiopancreatogram (ERCP) in an otherwise healthy patient with suspected malignant obstructive jaundice. Three other cases of acute cholecystitis have been reported in the literature after ERCP. Although not proven to prevent infectious complications during ERCP, strong consideration should be given to prophylactic antibiotics in patients with suspected malignant obstruction and/or coexistent medical illness, eg, diabetes. When attempts at decompression of the obstructed biliary system by endoscopy fail, decompression by percutaneous or surgical routes should be considered in a timely fashion.

Acute Disease↗

PubMed1994

Cytokine-mediated gene therapy for cancer.

BACKGROUND: Significant interest has been generated in the gene therapy of cancer. One strategy involves tumor-directed cytokine gene transfer and its effects on tumor immunobiology. METHODS: The authors review the current literature pertaining to cytokine gene therapy of cancer and provide a description of gene transfer methods currently being evaluated. RESULTS: Several cytokine gene transfer models have been described involving at least 12 different cytokines. The introduction of cytokine genes into experimental animal tumors improves their ability to be recognized and destroyed by the host immune system. Certain cytokines will regulate phenotypic properties such as major histocompatibility complex antigens, immunosuppressive peptides, protooncogenes or endogenous cytokine production. Cytokine-transduced tumors attract an inflammatory exudate in vivo that generally results in tumor destruction. The nature of the infiltrate (lymphocytic, mononuclear, granulocytic) cannot always be predicted from the known biological properties of each cytokine. Untransduced bystander tumor cells are usually also destroyed. Some, but not all, cytokine transductions result in the generation of systemic major histocompatibility complex-restricted, tumor immunity. It has been hypothesized that the local continuous production of cytokines by tumor cells provides an optimal microenvironment for antigen recognition and the generation of T-cell immunity. CONCLUSIONS: These experimental observations hold promise for the clinical application of genetically engineered tumor vaccines.

Animals↗

PubMed1994

Patterns of class inequality in health through the lifespan: class gradients at 15, 35 and 55 years in the west of Scotland.

Data confirming the existence of social inequalities in health have continued to accumulate since the Black Report reported class inequalities across a broad range of causes of mortality, with an increasing emphasis on indicators of morbidity and current health status. Although evidence of continuing inequalities mounts, elucidation of underlying mechanisms generating and maintaining such inequalities has been more elusive, and much of the debate has oscillated from the very broad to the very specific. In this paper, the class patterning of a range of non-fatal indicators of health are modelled in an attempt to outline first the adequacy of models of linear relationships for this range of measures, and secondly, the extent to which these are generalizable across a series of age/sex subgroups and across different domains of health. Data are presented here for representative community samples of men and women in adolescence, early- and late-midlife. While orderly relationships between social class and health were seen for the majority of the measures considered; the detailed patterns show considerable diversity. Thus for some aspects of health, notably height (itself often heralded as a broad indicator of health and early life experience), common class gradients were observed for both sexes at each of the stages of the life course examined. For others (notably mental health and presence of chronic illness), gradients were evident in later life but not in adolescence. Others still showed sex but not age differences in class patterning (typically measures of body shape), or no clear patterns (notably blood pressure and consultations with general practitioners). The current analysis draws attention to the consistency of gradients in early- and late-midlife, which are apparent despite the marked increase in the burden of poorer health which manifests between these life stages for almost all indicators of health (an exception being mental health). The challenges which this presents for understanding the mechanisms and processes which have been candidate explanations for social inequalities in health are discussed.

Adolescent↗

PubMed1994

Coronary risk in a British Punjabi population: comparative profile of non-biochemical factors.

OBJECTIVES: To develop a profile of non-biochemical coronary risks for the South Asian population (predominantly Punjabi with origins in the Indian subcontinent) and the general population in Glasgow, with a focus on dietary patterns, and potential causes of stress. DESIGN: Cross-sectional survey of South Asian men and women of 30-40 years (mean 35), compared with a general population sample aged 35 years. MEASUREMENTS: Data were collected on socioeconomic circumstances, smoking, diet, alcohol, exercise, past health, perceptions of stress and other psychological morbidity, blood pressure, height, weight and waist and hip girth. RESULTS: The socioeconomic circumstances of the South Asian group were worse than the general population. The prevalence of several circumstances potentially associated with stress, such as length of working day, low income, crowded housing, liability to attack and perceived lack of social support (women), was greater in South Asians. Smoking was less common in South Asians, particularly among women and non-Muslims. Amongst South Asians, alcohol use was uncommon in women and Muslims. South Asians ate meat, and fruit, salad and raw vegetables more frequently than the general population though there were large variations by religion. South Asian men were less likely to take vigorous exercise than the general population. Diastolic, but not systolic, blood pressure was higher in South Asian males than general population males, but there were no differences among women. Men were shorter and weighed less than general population men, with no difference in body mass index. South Asian women were shorter but had higher mean body mass index than the general population. Waist and hip circumference in both South Asian men and women were higher although waist/hip ratios were not different. Self-reported diabetes was commoner in Asian men than in general population men, and angina symptoms commoner in South Asian women. CONCLUSIONS: Among established risk factors studied here or reported in an earlier paper the only one to which South Asians had less exposure was smoking. In either men or women (or both) there was a relative excess of the other known risk factors. There was evidence in support of three newer hypotheses for the high incidence of coronary heart disease (CHD), namely, insulin resistance, stress, and socioeconomic deprivation. The high CHD rates in South Asians are likely to result from a complex interaction of risk factors.

Adult↗

PubMed1994

How sick is the West of Scotland? Age specific comparisons with national datasets on a range of health measures.

The Central Clydeside Conurbation (CCC) has relatively high mortality rates. This paper examines whether it also has relatively high rates of ill health, using data from three cohorts (aged 15, 35 and 55 in 1987/88) in the West of Scotland. Comparisons on a range of self-reported physical and mental health indicators, anthropometric measures, blood pressure, and respiratory function were made with comparable age groups in ten British or Scottish national studies. The older two cohorts in the CCC exhibited relatively high rates of longstanding and limiting longstanding illness and the youngest cohort had relatively poor psychosocial health, compared to their age peers elsewhere. Fewer differences were found in blood pressure, anthropometric measures or respiratory function although older CCC residents were slightly shorter than in Britain as a whole and had slightly poorer respiratory function. Central Clydesiders in the late 1980s were generally in poorer health than those of the same sex and similar age elsewhere in the UK, but the extent of the disadvantage varied across different dimensions of health, and was not as marked as some stereotypes of the West of Scotland would suggest.

Adaptation, Psychological↗

PubMed1994

Stereotactic delivery of a recombinant adenovirus into a C6 glioma cell line in a rat brain tumor model.

The dismal results of conventional therapy for primary malignant brain tumors has justified exploring gene therapy approaches for this disease. Transduction of animal brain tumor models in vivo has been reported previously with retroviruses and herpes viruses. Because adenoviruses have the advantage of transducing quiescent and actively dividing tumor cells, they may prove to be more effective in such therapy. We used a replication-deficient recombinant adenovirus bearing the Escherichia coli beta-galactosidase gene in a rat C6 glioma tumor model. Transduced cells were detected by X-5-bromo-4-chloro-3-indolyl beta-D-galactoside staining to reveal beta-galactosidase activity. Initial experiments in vitro showed 50% and 90% transduction at vector titers of approximately 10(7) and 10(8) plaque-forming units/ml, respectively. Although no cytopathic effects were seen at 10(7) plaque-forming units/ml, more than 50% reduction in tumor cell growth was noted at 10(8) plaque-forming units/ml both in vitro and in vivo. Stereotactic delivery of the recombinant adenovirus into the frontal lobe of normal rat brains resulted in intense staining of all cell types, that is, neurons, astrocytes, and ependymal cells. Stereotactic injection into C6 glioma brain tumors in rats stained 25 to 30% of the tumor cells. We conclude that adenovirus vectors can be used to transfer genes to central nervous system tumors in vivo. Using stereotactic delivery, adenovirus vectors can transfer genes into the central nervous system intended for tumor therapy.

Adenoviridae↗

PubMed1994

Breast cancer risk and hormone replacement therapy: a review of the epidemiology.

Hormone-related cancers account for more than 20% of all newly diagnosed malignancies and more than 40% of all female cancers in the United States. The life-time odds of getting breast cancer in North America are now one in eight. Mortality rates have held almost steady over the past 20 years, even though the number of new cases has grown. The impact of exogenous hormones on risk of reproductive cancer, especially breast cancer, has been the focus of considerable interest in recent years as the use of exogenous hormones (both pre-menopausally and post-menopausally) has increased. Evidence concerning the effect of hormone replacement therapy (HRT) on breast cancer risk is presented. The epidemiology of other risk factors for breast cancer is summarized as background; this includes reproductive factors (such as age at first birth, and age at menarche and menopause), family history, and use of exogenous hormones other than HRT.

Age Factors↗

PubMed1993

Health of a Punjabi ethnic minority in Glasgow: a comparison with the general population.

OBJECTIVE: To compare common health experiences of a South Asian (predominantly Punjabi) population with that of the general population, according to sex, and to related patterns of health in the fourth decade of life to the pattern of hospital admission and mortality documented in the published reports. DESIGN AND SETTING: A cross sectional survey with interviews and physical measures was undertaken in a two stage stratified random cluster sample in the city of Glasgow. SAMPLE: This comprised 159 South Asians aged 30-40 years, mean age 35 (73.6% of those invited) and 319 subjects from the general population, all aged 35 years. MEASUREMENTS AND MAIN RESULTS: Body structure, lung function, pulse and blood pressure, history of physical and mental health, results of standardised questionnaires on mental health, angina and respiratory health, recent and past symptoms, history of accidents, and sickness behaviour were determined. South Asians were shorter, broader, and more overweight (women); they had lower values for forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), a faster pulse, and higher diastolic pressure (men). Fewer South Asians had had accidents or digestive symptoms (men); more had psychosomatic and high total symptoms (women); fewer wore glasses, had lost teeth, or had long standing illness (men) (all p < 0.01). Women had a lower FEV1/FVC ratio (p < 0.05). CONCLUSIONS: South Asians were consistently disadvantaged only in terms of anthropometric measures. Otherwise, the many differences were balanced, with disadvantage being concentrated only among South Asian women. The health gap between sexes in South Asians seems higher than in the general population. The findings show patterns of health in the fourth decade of life which are consistent with patterns of hospital admission and mortality documented in the published reports.

Adult↗