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Biomedical subjects

J McIntosh

Publications and source records attributed to J McIntosh.

At least 19 recordsLinked to original sources
PubMed2006

Nicotine and smoker status moderate brain electric and mood activation induced by ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist.

As the increased smoking prevalence in schizophrenics may be interpreted as an adaptive response to an underlying biological defect, investigations into nicotine's actions within N-methyl-d-aspartate (NMDA) antagonist drug models of schizophrenia may improve our understanding of the role of glutamatergic neurotransmission in initiating and maintaining nicotine dependence in this disorder. In this double-blind, placebo-controlled, randomized study, the electroencephalographic (EEG) and subjective response to a sub-psychotomimetic intravenous dose of the NMDA antagonist ketamine was examined in 20 regular smokers and 20 non-smokers pretreated with placebo or nicotine gum. Although nicotine increased EEG arousal, ketamine produced electrocerebral signs of brain activation (decreased slow wave power) and sedation (decreased fast wave power and frequency), which were not affected by nicotine pretreatment and were evident only in non-smokers. Ketamine increased a number of self-report indices of subjective arousal, some of which were attenuated and potentiated by nicotine in smokers and non-smokers, respectively. These findings suggest that long-term (evidenced by smoker vs. non-smoker comparisons) and short-term (acute) nicotine exposure may alter NMDA receptor-mediated arousal and mood systems in a way that promotes nicotine dependence in smokers, and addresses neurobiological deficiencies in smokers with schizophrenia.

Adult↗
PubMed2006

Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes.

IGF-binding protein (IGFBP)-3 is generally considered to have actions that counterbalance those of IGFs and is therefore being developed as a cancer treatment. In breast tumors, however, high levels are associated with aggressive tumors and poor prognosis. Consistent with this we have demonstrated that although IGFBP-3 and a non-IGF-binding fragment (serine phosphorylation domain peptide) reduced attachment and enhanced apoptosis of Hs578T breast cancer cells cultured on collagen or laminin, it promoted their attachment and survival on fibronectin, which is abundant in the matrix of aggressive tumors. We have now examined the factors that determine whether IGFBP-3 has positive or negative actions on breast epithelial cells. IGFBP-3 also promoted survival of Hs578T cells in the presence of an antibody to the beta1-integrin subunit or when cholesterol-stabilized complexes were disrupted. These actions were blocked by IGF-I or a MAPK inhibitor. Serine phosphorylation domain peptide had similar actions on MCF-7 cells that were again reversed on fibronectin or with disruption of cholesterol-stabilized complexes and blocked by the beta1-integrin antibody. In contrast, IGFBP-3 promoted growth and survival for nonmalignant MCF-10A cells, but these effects were again reversed on fibronectin and blocked by the beta1 antibody or a MAPK inhibitor or by disruption of cholesterol-stabilized complexes. On Hs578T cells, IGFBP-3 bound to caveolin-1 and beta1-integrins, enhancing their aggregation, the recruitment of focal adhesion kinase, and the activation of MAPK. In summary, with three breast epithelial cell lines, IGFBP-3 had positive or negative effects on growth and survival dependent upon the status of cholesterol-stabilized integrin receptor complexes.

Apoptosis↗
PubMed2005

Pulmonary staging in colorectal cancer--is computerised tomography the answer?

INTRODUCTION: Pulmonary staging in colorectal cancer (CRC) has traditionally been carried out by means of plain chest radiograph (CXR), although computerised tomography (CT) imaging of the chest is increasingly being performed for this purpose. The aim of this study was to assess the value of pre-operative thoracic CT for pulmonary staging in CRC. PATIENTS AND METHODS: Data were collected prospectively on all patients referred into hospital over a 20-month study period for double contrast barium enema evaluation of symptoms suggestive of an underlying CRC. Patients with a CRC went on to have a staging intravenous, contrast-enhanced CT of the chest, abdomen and pelvis prior to an out-patient appointment with a colorectal surgeon. The CXRs of those patients in whom a radiological abnormality was seen on thoracic CT were reviewed blindly by an independent consultant radiologist. RESULTS: A total of 403 barium enemas were performed, of which 38 demonstrated a CRC (9%). In those patients diagnosed with CRC, nine (24%) had an abnormality on thoracic CT. Four patients with positive thoracic CTs had chemotherapy and or radiotherapy with no surgery. One patient underwent colectomy, and 2 patients who had primary lung tumours as opposed to metastases also underwent colectomies. One patient received palliative care only. In addition, one of the patients underwent multiple, non-diagnostic thoracic investigations prior to a diagnosis of sarcoidosis being made and then proceeding to surgery. An independent consultant radiologist reviewed seven out of the nine CXRs of patients with an abnormality on thoracic CT without knowledge of the clinical diagnosis, and reported three of the CXRs to be normal. CONCLUSIONS: Thoracic CT appears to improve the accuracy of pulmonary staging in CRC allowing a more appropriate level of intervention. However, CT is likely to identify more benign radiological abnormalities than CXR alone, and investigations should not occur to the detriment of treating the primary tumour.

Aged↗
PubMed2002

Audit of attendance rates for an infra-inguinal graft surveillance programme--how complete is your graft surveillance?

Much has been written on the subject of graft surveillance following infra-inguinal bypass graft surgery, but surprisingly little information exists on actual attendance rates for such programmes. The aim of this study was to calculate the attendance rate for graft surveillance at the vascular unit in Cheltenham. All patients who entered the graft surveillance programme following an infra-inguinal graft procedure over a 5-year period were included in the study. Partial and complete surveillance attendance rates were calculated for each year in the study period. Both rates were seen to rise over the 5-year period, from 31% to 78% and 0 to 38%, respectively. These attendance rates were much lower than were expected. Vascular units relying on such graft surveillance programmes should evaluate their own 'surveillance rates'.

Ambulatory Care↗
PubMed2001

Changes in general health and musculoskeletal outcomes in the workforce of a hospital undergoing rapid change: a longitudinal study.

This article aimed to examine changes in general health and time with back pain and neck pain and to identify predictors of any such changes. Hospital workers were studied longitudinally with surveys in 1995, 1996, and 1997 (N = 712). Back and neck pain were reported only at the 2nd and 3rd surveys. There was a significant decline in general health and significant increases in time with neck pain and back pain. Predictors of changes in these outcomes were mainly work-related variables (initial or change values), such as job interference with family, job influence, work psychological demands, and hours worked.

Adult↗
PubMed2001

An economic analysis of surgical wound infection.

Audit of surgical wound infection is not only an outcome indicator, but also an important aspect of infection control. The literature suggests an expensive 'gold standard' involving a full-time audit nurse collecting prospective data, including a 30-day follow-up into the community.Our study indicates that the cost of surgical wound infection is three-fold: cost to the hospital, the community services and the patient. Although the greatest costs were due to prolonged stay or re-admission to hospital (just under pound90 000), costs to the community and patient cannot be ignored. Hospital expenditure varied according to the type of operation. The study clearly demonstrated the potential cost savings to be highlighted by this type of audit.

Costs and Cost Analysis↗
PubMed2001

Regulation of bleomycin-induced DNA breakage and chromatin structure in lung endothelial cells by integrins and poly(ADP-ribose) polymerase.

Activation of endothelial cell integrins inhibits DNA breakage by diverse agents, including the DNA-damaging agent bleomycin. DNA breaks activate nuclear poly(ADP-ribose) polymerase (PARP), which regulates chromatin structure and DNA repair. We determined the role of PARP in suppression of bleomycin genotoxicity by integrins using wild-type and PARP knockout mouse lung endothelial cells (MLEC), and the PARP inhibitor, 3-aminobenzamide (3AB). Activation of beta1 integrins by antibody clustering enhanced the sensitivity of wild-type nuclei to digestion with micrococcal nuclease and deoxyribonuclease I, indicating that chromatin structure was altered. 3AB blocked this effect. Knockout and 3AB-treated wild-type MLEC were hypersensitive to deoxyribonuclease I compared with wild-type cells, demonstrating that PARP regulates chromatin structure. Integrin clustering reduced the hypersensitivity of knockout cells, suggesting additional, PARP-independent mechanisms that inhibit nuclease interaction with chromatin. Bleomycin caused DNA breakage in wild-type and knockout MLEC. Breaks were eliminated after 60 min incubation of wild-type cells in drug-free medium, whereas 3AB or PARP knockout inhibited DNA repair. Integrin clustering protected wild-type cells from DNA breakage, and 3AB and PARP knockout inhibited this protection. Bleomycin caused large increases in PARP activity in wild-type but not knockout MLEC, and integrin clustering inhibited the activation of PARP. The results indicate that the antigenotoxic effects of integrin activation require PARP and that integrins alter chromatin structure by PARP-dependent and -independent mechanisms.

Animals↗
PubMed2000

Addicts' narratives of recovery from drug use: constructing a non-addict identity.

Sociological accounts of the process of recovery from dependent drug use have emphasised the importance of the individual constructing a non-addict identity for themselves. Following Giddens we identify the process of providing a narrative of their recovery as one of the mechanisms by which addicts may seek to achieve this. The narratives of recovery which are the subject of this paper were elicited in the course of semi-structured interviews with a sample of 70 recovering addicts. There were three key areas in which the addicts' narratives of recovery could be seen to be constructing a non-addict identity for the individual; firstly, in relation to the reinterpretation of aspects of their drug using lifestyle; secondly, in relation to the reconstruction of their sense of self and thirdly, in relation to the provision of convincing explanations for their recovery. In certain respects, the addicts' narratives of recovery are similar to the accounts of recovery provided by drug workers and addictions researchers. The paper argues that the correspondence between addicts' own accounts of their recovery and those of professional drug workers may be not so much the result of the intrinsic nature of the recovery process as a product of the socially constructed nature of the narratives and the fact that the latter may have been developed in conjunction with those working in the drug treatment industry.

Adult↗
PubMed2000

Predictors of job stress and satisfaction among hospital workers during re-engineering: differences by extent of supervisory responsibilities.

After two years of rapid organizational change within a large teaching hospital, 83 percent of workers remained employed there. Among these "survivors," job satisfaction decreased and job stress increased regardless of whether they were employed in a supervisory position. This article examines the predictors of job satisfaction and job stress for managers, for people who indicated that they supervised others but were not managers, and for workers. There are areas of commonality in predictors across these groups, as well as some differences by level of supervisory responsibility. Examining and modifying job characteristics associated with high stress could result in healthier hospital work environments.

Hospital Administrators↗
PubMed2000

Factors associated with consulting medical or non-medical practitioners for dyspepsia: an australian population-based study.

BACKGROUND: Little is known about how many dyspeptics in the population consult medical and non-medical practitioners, or the factors associated with various consulting patterns. METHODS: A cross-sectional survey of 748 Australians with dyspepsia investigated their age, sex, dyspepsia symptoms, medical and non-medical consultations, and health status on the SF-12. RESULTS: Overall, 56% had ever consulted a medical practitioner for dyspepsia. Of these, 54% consulted within 6 months of first symptoms. Non-medical practitioners were consulted by 29%. Compared to dyspeptics in all, or most, other consulting groups, subjects who did not consult (37%, group NO) were characterized by fewer symptoms, better physical health, and younger age. Those who only consulted doctors (34%, group M) were older and had better mental, but poorer physical health. Those who only consulted non-medical practitioners (7%, group N) were younger and had better physical, but poorer mental health. Dyspeptics consulting both medical and non-medical practitioners (22%, group M + N), were older, more dissatisfied with medical care, had more symptoms and poorer physical and mental health. Timing of medical consultations was similar in groups M and M + N. Group M + N dyspeptics consulted similar types, but more non-medical practitioners than group N. No sex differences were found in consulting behaviour. CONCLUSIONS: Many dyspeptics do not consult; they have fewer symptoms than consulters. Consultation with non-medical practitioners is common and is associated with poor mental health. Dyspeptics seeking advice from both medical and non-medical practitioners are less satisfied with their medical management than those who only consult doctors for their dyspepsia.

Adult↗
PubMed2000

The use of simulation and post-simulation interview to examine the knowledge involved in community nursing assessment practice.

This paper describes the development of an innovative research approach which used the complementary methods of simulation and post-simulation interview to examine the knowledge-base involved in community nursing assessment practice in the United Kingdom. The study commenced in 1994 and the main phase of data-gathering took place over a 3-week period in 1995. Having outlined the study's aim, context and theoretical background, this paper focuses on the two main methods of data-gathering used. Detailed description of the simulation method and the post-simulation interview and the rationales for their use are followed by critical discussion which identifies their particular strengths and weaknesses. Threats to validity are also considered. It is argued that the combined use of a simulated assessment and a post-simulation structured interview has great potential as a means of exploring the knowledge involved in community nursing assessment practice.

Community Health Nursing↗
PubMed2000

Evolutionary change in the use of skills within the district nursing team: a study in two Health Board areas in Scotland.

Grade mix within the district nursing team in the United Kingdom has changed markedly over the last 10 years but the relationship between grade mix and skill mix has received only intermittent research attention. This study adopted an ethnographic approach and aimed to explore the way in which grade and skill are taken into account in the delegation of nursing care. After gaining ethical approval, a total of 76 members of 21 district nursing teams in two areas were observed and interviewed. Delegation practices were found to vary both within and between areas and considerable differences were uncovered in the responsibilities allocated to more junior and unqualified team members. The developing role of nursing auxiliaries is discussed in relation to the role of the G grade sister, resource constraints and the standards of patient care. The paper concludes by arguing that the supervision and leadership role provided by the G grade sister should be fully recognized and safeguarded.

Attitude of Health Personnel↗
PubMed1999

Short- and long-periods of neonatal maternal separation differentially affect anxiety and feeding in adult rats: gender-dependent effects.

Environmental manipulations during early development can induce permanent alterations in hypothalamic-pituitary-adrenal (HPA) and behavioral responses to stressors. However, little is known about the impact of early life experiences on appetitive responses. The present investigation assessed the effects of brief handling/separation or protracted separation from the dams, on feeding and anxiety responses during development. During the first 3 weeks post-partum, Sprague-Dawley rat pups were exposed daily to either brief (15 min) handling/isolation (H), a more protracted (3 h) period of maternal separation (MS), or were not handled (NH). When tested on the elevated plus-maze (at 5-6 weeks) H groups displayed less anxiety than NH gender-matched controls. Surprisingly, so did the MS females. At weaning (Day 22), the MS rats weighed significantly less than both the H and NH animals; the difference between the H and MS was more robust and persisted throughout the experiment (D 62). The H animals of both genders, and the females of the MS group, consumed more of the palatable 'snack' than their NH counterparts. The feeding suppressant response to the various satiety peptides (bombesin, cholecystokinin, and amylin) was not affected by the early life experience, with exception of cholecystokinin (CCK) effects, which were more pronounced in H and MS males. These results suggest that early life events may contribute to anxiety and/or ingestive disorders such as anorexia nervosa, bulimia and obesity.

Amyloid↗
PubMed1999

Determinants of job stress and job satisfaction among supervisory and non-supervisory employees in a large Canadian teaching hospital.

This article explores the extent to which hospital workers at a large teaching hospital at different managerial/supervisory levels (designated and non-designated supervisors, and non-supervisory staff), experienced job stress and job satisfaction prior to the re-engineering of hospital services. For all groups, increased levels of job demands were associated with higher levels of stress. Lower levels of decision latitude were associated with increased job stress for designated supervisors. Increasing levels of decision latitude were associated with both job stress and satisfaction for the other two groups. Co-worker support and teamwork contributed to increased job satisfaction for all groups.

Adaptation, Psychological↗
PubMed1999

Role of bombesin-related peptides in the control of food intake.

In 1970, Erspamer et al.(1,14)isolated and characterized the tetradecapeptide bombesin (BN) from the skin of amphibian frog Bombina bombina. Subsequently, several BN-like peptides have been identified in mammals, consisting of various forms of gastrin-releasing peptide (GRP) and/or neuromedin B (NMB), together with their distinct receptor subtypes. It has been proposed that BN-related peptides may be released from the gastrointestinal (GI)-tract in response to ingested food, and that they bridge the gut and brain (through neurocrine means) to inhibit further food intake. Conversely, the suppression of release of BN-like peptides at relevant brain nuclei may signal the initiation of a feeding episode. The present review will describe recent pharmacological, molecular, behavioral and physiological experiments, supporting the contention that endogenous BN-related peptides do indeed influence ingestive behaviors. Particular attention is focused on the relationship between these peptides in the peripheral compartment and their impact on central circuits using GRP and/or NMB as transmitters. In addition, however, we will point out various caveats and conundrums that preclude unequivocal conclusions about the precise role(s) of these peptides and their mechanism(s) of action. We conclude that BN-related peptides play an important role in the control of food intake, and may contribute to ingestive disruptions associated with anorexia (anorexia nervosa, AIDS and cancer anorexia), bulimia, obesity and depression. Hence, pharmacological targeting of these systems may be of therapeutic value.

Animals↗
PubMed1999

The impact of re-engineering and other cost reduction strategies on the staff of a large teaching hospital: a longitudinal study.

OBJECTIVES: To examine changes over time in the hospital staff's perceptions of how rapid organizational change, caused by fiscal constraints imposed by governments, affects them, their work environment, and the quality of care and services that they provide. METHODS: A random sample of hospital employees (n = 900) of a large Ontario teaching hospital participated in a longitudinal study which involved surveys at 3 measurement periods over a 2-year period. The questionnaire used in this study included scales reflecting work environment, emotional distress, personal resources, spillover from work to home and vice versa, and perceptions regarding patient care and the hospital as an employer. RESULTS: Significant increases in depression, anxiety, emotional exhaustion, and job insecurity were seen among employees, particularly during the first year of the change process. By the end of the second year, employees reported deterioration in team work, increased unclarity of role, and increased use of distraction to cope. Job demands increased throughout the period whereas little change occurred in the employee's job influence or decision latitude. Overall, the work environment was negatively affected. Although patient care was unaffected in the first year, a significant decline in perceptions of patient care, attention to quality improvement, and overall quality of care were later seen. CONCLUSIONS: This study raises questions about whether hospital re-engineering and mergers will be able to achieve the cost reductions sought without sacrificing quality of work life. Along with the rapid change, there was increase in emotional distress among staff and a deterioration in their relationship with their employer.

Adaptation, Psychological↗