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Biomedical subjects

J Irvine

Publications and source records attributed to J Irvine.

At least 37 records · Page 2Linked to original sources

A longitudinal study of psychological adjustment to familial genetic risk assessment for ovarian cancer.

OBJECTIVES: To evaluate the psychological adjustment of women during initial genetic ovarian cancer risk assessment and at clinic follow-up, 6-12 months later. METHODS: Sixty-five subjects were assessed with the Centre for Epidemiological Studies Depression Scale (CESD), Spielberger's State Anxiety Inventory, and an 18-item, investigator-designed questionnaire yielding self-report on screening responses, worry about increased risk, identification of cancer-related deaths in relatives, worry about future cancer risks of daughters, alteration of future plans as a result of ovarian cancer risk, etc. RESULTS: Thirty-three percent of subjects had CESD scores above the established cutoff for depression at baseline and 38% had scores above cutoff at follow-up. Sixteen percent of subjects had state scores on the State-Trait Anxiety Inventory higher than 1 standard deviation above average (norm) at baseline, while only 6% had scores higher than 1 SD above average at follow-up. CONCLUSION: To identify factors associated with self-reported depression at follow-up, a series of demographic and self-reported variables (e.g., presence of identified problems in family, impact of genetic risk information, concern for daughter in the future) were entered in a multiple regression analysis with the CESD follow-up score as the dependent variable. Only one predictor accounted for a significant amount of variance in depression scores. Concern for daughter's risk in the future was associated with higher depression scores at follow-up (R = 0.33, P<0.02, R(2) = 11%).

Adaptation, Psychological↗

Evidence for continued transmission of parasitic nematodes in reindeer during the Arctic winter.

Living in the high Arctic, the Svalbard reindeer (Rangifer tarandus platyrhynchus) and its trichostrongyle nematodes experience a long cold winter from October to late May/early June. Over this period, transmission would be expected to be low. However, in culled reindeer the abundance of infection increased from autumn to late winter, providing evidence for continued transmission within this period. To our knowledge this is the first time this has been demonstrated in a climate with temperatures consistently below 0 degrees C. In one winter (1996-1997), the average fraction of nematodes found as larvae in the abomasal mucosa increased from around 10% to 50% between October and March. This suggests that arrested development took place throughout the winter. We found no evidence for an efficient acquired immune response towards the nematodes. The abundance of infection did not tend to decrease with increasing host age after an earlier peak, but levelled off instead, as predicted by a simple immigration-death model. In the late winter when the nutritional plane is low, both adult reindeer and calves had high worm burdens at intensities that may affect their condition and fitness.

Abomasum↗

The patient's motivation in seeking complementary therapies.

The motivations of cancer patients in seeking complementary therapies are, fundamentally, self-healing motivations which, when engaged appropriately, can contribute to the patient's psychological and physical well being. In this paper, we apply a theoretical model, the Risk Adaptation Model, to furthering the clinical understanding of the motivations of cancer patients in seeking complementary therapies. The model identifies six discrete cognitive processes which, in combination, are hypothesized to play a central role in therapy seeking. Emphasis in this model is placed on the patient's need to maintain positive expectancies (optimism) when faced with the risk and uncertainty of cancer. This understanding of complementary-therapy seeking is grounded in the perspective that clinicians must respect the autonomy of cancer patients in their quest for appropriate therapies, and assist rather than direct their process of therapy-seeking.

Adaptation, Psychological↗

Development and testing of a new hostility scale.

Evidence suggests that assessment of global type A behaviour as a coronary risk factor may not be the most fruitful strategy because some components, particularly hostility, may be more harmful than others. Measurement of hostility has been primarily through two types of instrumentation: the Type A Structured Interview (SI) and the Cook-Medley (Ho) scale. Deficiencies in the measurement of hostility have resulted from a lack of conceptual clarity because definitions of hostility have been blurred by overlap with the concepts of anger and aggression. The main objective of this study was to develop and test an instrument that focuses hostility on attitude rather than emotion or behaviour. Psychometric properties of the Hostile Attitude Scale (HAS) were Cronbach's alpha, 0.80, and correlation of 0.56 with the Ho scale and 0.43 with the SI. In a clinical investigation that used the HAS, SI and Ho scale, all measures were significantly correlated with angiogram outcome, although the strongest relationship was with the HAS. Hostile attitude alone (HAS) accounted for 6% of explained variance in angiogram outcome based on regression analysis. The HAS is offered as a short, easily administered measure of hostility, with particular emphasis on cognitive aspects of the construct.

Coronary Disease↗

Tumours derived from HTLV-I tax transgenic mice are characterized by enhanced levels of apoptosis and oncogene expression.

In order to investigate the role that the human T-lymphotropic virus type I (HTLV-I) tax oncogene plays in apoptosis and transformation in vivo, four lines of HTLV-I tax transgenic mice were generated under the regulatory control of the CD3-epsilon promoter-enhancer sequence. These mice develop a variety of phenotypes including mesenchymal tumours, which develop at wound sites, and salivary and mammary adenomas. In situ DNA fragment labelling and immunocytochemical analysis of these tumours reveals that they display enhanced levels of apoptosis, which is associated with elevated levels of Myc, Fos, Jun, and p53 protein expression. Furthermore, double immunofluorescent staining shows that Tax expression and apoptosis co-localize, indicating that Tax expression is closely associated with apoptosis in vivo.

Adenoma↗

Changes in the zymogenic cell populations of the abomasa of sheep infected with Haemonchus contortus.

The effects of dietary urea supplementation and of a 10-week trickle infection regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic population of the abomasa of Hampshire Down lambs was examined. At necropsy a variety of parameters including plasma pepsinogen concentration, the wet weights of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in them, were assessed. Tissue pepsinogen concentration was measured as the total, acid-stable proteolytic activity present in mucosal homogenates, as well as immunohistochemically. The immunohistochemical findings were quantified using computer-aided image analysis. Elevation of plasma pepsinogen concentrations in infected animals was of borderline significance (P = 0.06). The fundic mucosae of infected animals were heavier (P < 0.02) than those of control animals, but there was no overall change in the pepsinogen content of tissues. Immunohistochemistry revealed that infected animals had increased numbers of zymogenic cells, due to mucous cell hyperplasia and the adaptation of cells to produce both mucins and pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen in uninfected animals, was reduced in infected lambs. Image analysis confirmed that at a mid-point of the mucosa of infected animals there was increased pepsinogen-specific immunoreactivity that corresponded with areas of mucosal hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of pepsinogen secretion in infected animals even if chief cell output is reduced.

Abomasum↗

Autonomic correlates of antidepressant treatment using heart-rate variability analysis.

OBJECTIVE: To assess the 24-hour temporal-domain heart-rate variability correlates of treatment with fluoxetine or doxepin for depression. METHOD: A randomized evaluation of fluoxetine and doxepin measured a 50% change in the Hamilton Depression Rating Scale (HDRS) score as a response to therapy and was correlated with measures of standard deviation of the mean of all 5-minute segments of normal electrocardiographic R-R intervals (SDANN), standard deviation of all normal R-R intervals (SDNN), root mean square of successive differences in R-R intervals (r-MSSD), and percentage difference between adjacent normal R-R intervals that are greater than 50 msec (pNN50) from 24-hour electrocardiogram (ECG) tapes. RESULTS: Ten out of 14 patients responded. Response was associated with an increase in SDANN of 17% (P < 0.05). Nonresponse was associated with a 17% decrease in SDANN and a 22% decrease in SDNN (both P < 0.05). No other measures correlated with therapeutic response. No heart-rate variability (HRV) differences between the 2 drug therapies were observed. CONCLUSION: Twenty-four-hour HRV measures may be useful in assessing response to antidepressant therapy.

Analysis of Variance↗

Effectiveness of fluoxetine and doxepin in treatment of melancholia in depressed patients.

It has been suggested that serotonin reuptake inhibitors (SSRIs) may be less effective than tricyclic antidepressants (TCAs) in treatment of melancholic depression. We treated 36 depressed ambulatory patients with doxepin or fluoxetine in a double-blind, randomized 6-week trial with placebo run-in. Seven patients treated with doxepin and 13 patients treated with fluoxetine met diagnostic criteria for melancholic depression. Average daily dose was 169.4 +/- 41.6 mg for doxepin and 36.8 +/- 18 mg for fluoxetine. We observed a 50% response rate in both treatment groups, using as outcome criterion reduction of Hamilton Depression Scale Score to less than 10. Regardless of how strict the definition of response, we found fluoxetine to be as effective as doxepin in our group of melancholic outpatients.

Adult↗

Helplessness, self-efficacy, cognitive distortions, and depression in multiple sclerosis and spinal cord injury.

The aim of this study was to determine if learned helplessness, self-efficacy, and cognitive distortions would predict depression in a sample of 80 individuals with multiple sclerosis (MS) and 80 individuals with a spinal cord injury (SCI). As MS and SCI usually present with disparate disease courses and etiologies, a secondary objective was to determine if individuals with MS would exhibit greater levels of helplessness, cognitive distortions, and depression and lower levels of self-efficacy than those with SCI. Results indicated that helplessness and self-efficacy significantly predicted depression for both the MS and SCI groups after controlling for confounding variables. Cognitive distortions had no independent effect, indicating that cognitive distortions may have caused feelings of helplessness and low self-efficacy and, in this way, had indirect effects on depression. The MS group exhibited significantly greater levels of depression and helplessness and significantly lower levels of self-efficacy than the SCI group. It was hypothesized that it may have been the combination of an unpredictable course of disease activity and the possibility of being affected by MS in many different ways that produced greater feelings of depression, helplessness, and low self-efficacy in the MS group.

Adaptation, Psychological↗

The feasibility of assessing women's perceptions of the risks and benefits of fertility drug therapy in relation to ovarian cancer risk.

OBJECTIVE: To determine the feasibility of asking women undergoing fertility treatment the maximum increased risk of ovarian cancer they would be willing to tolerate in order to take ovulation-induction drugs. DESIGN: A prospective pilot study of women attending fertility clinics over a 2-month period. SETTING: Two tertiary care fertility clinics in Toronto. PATIENT(S): Sixty-one English-speaking women were approached and 85% (n = 52) were enrolled. INTERVENTION(S): A self-administered questionnaire with fertility-specific questions. Thirty-eight women also were asked to complete standardized scales of anxiety and optimism. MAIN OUTCOME MEASURE(S): Women's report of the maximum level of lifetime risk of ovarian cancer they were willing to tolerate in order to undergo fertility treatment. RESULT(S): Seventy-nine percent were willing to accept an increased risk of ovarian cancer. Only 24% understood that treatment for ovarian cancer usually was not curative. CONCLUSION(S): A majority of patients were willing to tolerate a modest increase in their lifetime risk of ovarian cancer because of fertility treatment, most basing their estimate of acceptable risk on limited awareness of the issue.

Adult↗

What role do patients wish to play in treatment decision making?

BACKGROUND: Although current ideology suggests patients should be active participants in decision making about their care, the literature suggests that patients wish to be informed but not involved. OBJECTIVE: To test the hypothesis that most patients want their physicians to take the responsibility for problem solving (PS, identifying the one right answer), but that many want to be involved in decision-making (DM, selecting the most desired bundle of outcomes) tasks. METHODS: Survey responses from 300 patients undergoing angiogram at a Toronto, Ontario, hospital were analyzed (response rate, 72%). Survey items included scales to measure desire for information and participation, including Autonomy Preference Index, the Krantz Health Opinion Survey, and the Deber-Kraetschmer Problem-Solving Decision-Making Scale measured on a scale from, 1 (doctor only) to 5 (patient only). RESULTS: Patients had a relatively high desire for information. On the Problem-Solving Decision-Making Scale, they overwhelmingly wished the PS tasks to be performed by or shared with the physician (98.4% of the 12 PS scores are between 1 and 3), but wanted to be involved in DM (78% of the 6 DM scores are between 3 and 5). Preference for handing over control to the physician was significantly greater for the vignette involving potential mortality (chest pain) than for the vignettes involving mainly morbidity (urinary problems) or quality of life (fertility). CONCLUSIONS: Although patients do not wish to be involved in PS tasks, few wish to hand over DM control to their physician. These findings suggest 2 major roles for clinicians--assisting patients in PS to structure choices and supporting them in making often difficult decisions.

Attitude to Health↗

Histologic classification and immunophenotype of lymphosarcomas in cats with naturally and experimentally acquired feline immunodeficiency virus infections.

Lymphosarcoma (malignant lymphoma) is the commonest hematopoietic tumor in the cat. Many cases are associated with feline leukemia virus (FeLV) infection, but epidemiologic and experimental data suggest that feline immunodeficiency virus (FIV) may also have a role in lymphomagenesis. In this paper, we describe the clinical presentation, histologic classification, and immunophenotype of lymphosarcoma in eight domestic cats with natural or experimental FIV infections. The tumors were often of unusual distribution, with the majority of cases conforming to the least common anatomic classification of "miscellaneous." Histopathologic and immunophenotypic analysis using a panel of anti-cat and cross-reactive anti-human monoclonal and polyclonal antibodies identified seven of these tumors as high-grade B cell lymphomas of the centroblastic or immunoblastic subtypes. The remaining case was a T-cell tumor associated with a concurrent FeLV infection. Our findings, together with the results of an analysis of FIV proviral DNA in these tumors, indicate that the B-cell lymphosarcomas were comparable to those observed in human and simian immunodeficiency virus infections and that the role of FIV in lymphomagenesis is indirect and related to the potential for malignant transformation during polyclonal B cell activation.

Animals↗

Behavioral effects of neonatal cocaine exposure using a rodent model.

This study examined the effects of neonatal cocaine exposure on behavior using a rodent model. Rat pups were implanted with intragastric cannulas on postnatal day (PND) 4 and artificially reared (AR) from PND 4-10. The AR groups included two cocaine doses (20 mg/kg per day and 60 mg/kg per day) and an AR control. A sham surgery control group was also included that was reared naturally by its dam. Offspring from these neonatal treatment groups were examined for suckling performance (PND 13), passive avoidance learning (PND 23-24), activity (PND 18-21), or spontaneous alternation (PND 21). Neonatal cocaine exposure had no effect on suckling measures or passive avoidance learning. Activity was increased in the 60 mg/kg per day cocaine group relative to controls. In addition, spontaneous alternation was delayed in the 20 mg/kg per day cocaine-exposed females relative to all other groups. These data suggest that neonatal cocaine exposure may alter performance on some relatively simple tasks. More work is clearly warranted to look at the effects of neonatal cocaine exposure on more complex behaviors.

Animals↗

Regulation of egg production, worm burden, worm length and worm fecundity by host responses in sheep infected with Ostertagia circumcincta.

Following infection with Ostertagia circumcincta there was considerable variation in worm burdens, worm size and number of inhibited larvae even among sheep matched for age, sex, breed, farm of origin and history of parasite exposure. There was also substantial variation among sheep in the concentration of mast cells, globule leucocytes, eosinophils, IgA-positive plasma cells and parasite-specific IgA in the abomasal mucosa. With the exception of faecal egg counts over time, the parasitological and immunological traits were all continually distributed among animals and sheep did not fall into discrete high and low-responder categories. The responses were correlated. Sheep with more mast cells also had more globule leucocytes, more eosinophils, more IgA plasma cells and greater amounts of parasite-specific IgA in the abomasal mucosa. Female worm length was strongly and positively correlated with the number of eggs in utero. Faecal egg counts were associated with variation in worm number and with variation in the number of eggs in utero. The worm burden was negatively correlated with the number of globule leucocytes in the abomasal mucosa, suggesting that worm numbers are regulated by immediate hypersensitivity reactions. Decreased female worm length was associated with an increased local IgA response to fourth stage larvae. The number of inhibited larvae was positively associated with the size of the local IgA response and positively associated with the size of the worm burden. The results suggest that variation among mature sheep in faecal egg counts is due, at least in part, to variation in local IgA responses which regulate worm fecundity and to variation in local immediate hypersensitivity reactions which regulate worm burdens.

Animals↗

Assessment of the cytotoxicity of the photosensitizing drug BPD verteporfin using human vascular smooth muscle cells in culture.

Photosensitizing drugs are selectively taken up by lipid-rich lesions such as atheromatous plaque which when exposed to light render the drugs cytotoxic. However, skin photosensitivity which persists for many weeks is a significant side effect. We investigated the cytotoxicity of a new photosensitizing drug, the benzoporphyrin derivative BPD verteporfin (Quadra Logic Technologies), which does not have this deleterious side effect. Vascular smooth muscle cells (VSMC) from normal human mammary and diseased human coronary arteries were grown in culture from explants and characterized with respect to their growth rates. The sensitivity to BPD with and without light was assessed by measuring viability after treatment. The lethal dose of drug for 50% viability loss (LD50) for BPD with light was approximately 12.5 ng/ml for mammary artery, with 52 +/- 8% cell survival (n = 6). The coronary artery VSMC from all patient sources, although differing significantly in growth rate, had a survival of 44 +/- 6% (n = 12) at the same concentration of BPD used for the mammary artery SMC (p = NS). Our results established the LD50 for BPD using human arterial sources of SMC and showed that the growth rates of the cells did not affect the cytotoxicity of the drug.

Cell Survival↗