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Biomedical subjects

J Murphy

Publications and source records attributed to J Murphy.

At least 145 records · Page 8Linked to original sources

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↗

IL-4R expression in AIDS-KS cells and response to rhIL-4 and IL-4 toxin (DAB389-IL-4).

Interleukin-4 (IL-4) is a pleiotropic cytokine affecting growth and differentiation of various cell types as well as regulating other cytokines. To study the effect of IL-4 on AIDS-related Kaposi's sarcoma (AIDS-KS) cells, we first examined the tumor cells for IL-4 receptor (IL-4R) expression. KS cells express a single 4 kB IL-4R-specific mRNA and 1828 +/- 408 high affinity IL-4 binding sites per cell with a dissociation constant (Kd) of 154 +/- 37 pM. Addition of recombinant human IL-4 (rIL-4) minimally inhibited AIDS-KS cell growth and expression of IL-6. We then studied the effects of a chimeric fusion toxin DAB389-IL-4 which exerts cellular toxicity only on cells expressing IL-4R. DAB389-IL-4 inhibited protein synthesis in AIDS-KS cells at low concentrations (IC50 of 5 x 10(-11) M). This effect was abrogated by neutralizing antibody to IL-4 (25D2). We conclude that KS cells express a functional IL-4R and this receptor could serve as a target for novel therapy with agents such as DAB389-IL-4.

Acquired Immunodeficiency Syndrome↗

Interleukin-2 fusion protein (DAB389IL-2) selectively targets activated human peripheral blood and lamina propria lymphocytes.

Activated mucosal T lymphocytes correlate with the intestinal inflammation of inflammatory bowel disease. Activated T cells elaborate interferon-gamma (IFN-gamma) and express high-affinity interleukin-2 (IL-2) receptors. The IL-2/diphtheria toxin fusion protein (DAB389IL-2) has been shown to specifically kill high affinity IL-2 receptor-bearing cells. We tested whether DAB389IL-2 could specifically target activated lamina propria lymphocytes. Lymphocytes were activated in vitro with phytohemagglutinin and IL-2 for 24-48 hr. Toxin efficacy was determined by the [14C]leucine incorporation, IFN-gamma ELISA, and flow cytometry. DAB389IL-2 (10(-11) M) inhibited protein synthesis by 80% in activated lamina propria lymphocytes. This inhibition was blocked by coculture of either excess IL-2 or a nonfunctional IL-2 diphtheria toxin mutant protein. DAB389IL-2 (10(-12) M) also significantly reduced the numbers of activated helper T cells and IFN-gamma levels in 24-hr cultures. DAB389IL-2 specifically targets activated IL-2 receptor-positive lamina propria lymphocytes and is a potential new therapeutic agent for patients with active inflammatory bowel disease.

Diphtheria Toxin↗

Evaluation of differential effects of carbohydrate and fat intake on weight gain, serum IGF-1 and erythrocyte Na+K+ATPase activity in suboptimal nutrition in rats.

OBJECTIVE: Suboptimal nutrition leads to growth delay, frequently without over clinical or biochemical signs. We hypothesize that changes in serum IFG-1 and erythrocyte sodium-potassium ATPase activity (ENKA) may be indices of suboptimal nutrition. METHODS: Male Sprague-Dawley rats were pair-fed for 4 weeks with balanced diets of different carbohydrate (CHO) to fat (FAT) ratios (3:1, 2:1, and 1:1) and three levels of energy intake (ad-libitum, 80%, and 60%), corrected for actual body weight). Daily weight gain and weekly tail growth were monitored while ENKA, serum total protein, T3, insulin and IGF-1 were measured after four weeks. Refeeding experiments were also performed with the 3:1 and 1:1 CHO:FAT diets, including 4 weeks of dietary restriction and one week of ad-libitum feeding. RESULTS: Weight gain, tail growth, and IGF-1 decreased (p < 0.05) in all groups after 1 week of dietary restriction. A decrease in ENKA (p < 0.05) was found in rats that consumed 60% of ad-libitum energy intake only after 4 weeks. At the end of dietary treatment, weight gain was higher (p < 0.05) in rats fed the 3:1 CHO:FAT diet. In contrast, when energy was restricted to 80% or 60% of ad-libitum intake, rats fed the 1:1 CHO:FAT diet gained more weight (p < 0.05) compared to the 3:1 and 2:1 CHO:FAT diets. After 1 week of refeeding body weight, tail growth and ENKA returned to control values while serum IGF-1 levels remained depressed. CONCLUSIONS: Acute nutritional changes are clearly detected by a reduction of serum IGF-1 while ENKA may be a useful index for assessing chronic suboptimal nutrition.

Animal Nutritional Physiological Phenomena↗

Screening questionnaires for bakers' asthma--are they worth the effort?

The use of a respiratory screening questionnaire is recommended annually to screen bakery workers in the UK. We compared questionnaire screening with other methods of detecting workers with asthmatic symptoms and then assessed the significance of these symptoms with careful investigation and follow-up. Reasons for questionnaire failures were then explored. A questionnaire was issued to 362 flour-exposed workers in a large bakery. All positive respondents to respiratory symptom questions were interviewed by an occupational nurse. Workers with occupationally related symptoms at this interview were referred to the chest clinic. In addition, workers with negative questionnaires were screened using attendance records, sick notes and direct workplace observations. Workers with frequent absence from work or sick notes with respiratory diagnoses were interviewed in the same manner as those answering the questionnaire positively and then referred to clinic. At clinic, a diagnosis was made for each worker on the basis of clinical assessment, spirometry, serial peak expiratory flow rate (PEFR) analysis and radioallergosorbent testing (RAST) testing for specific IgE. Using the clinic diagnoses, the referral routes were audited to assess the rates of case detection of asthma and occupational asthma. The respiratory screening questionnaire identified 68 workers with respiratory symptoms. Of these, 21 proceeded to full assessment. A diagnosis of asthma was made in five cases, one of which was bakers' asthma. In addition, 11 workers not reporting any symptoms by questionnaire were referred to clinic and five were diagnosed as having asthma. Screening questionnaires may lead to an underestimate of the prevalence of asthmatic symptoms and as such should not be used alone in workplace screening.

Adult↗

Determining and discerning expert practice: a review of the literature.

Although the nature and characteristics of expert practice have been described in the literature, the description is incomplete. How expertise is gained is not fully understood, and definitions of expert competencies have yet to be developed. Essential issues for education arise from the demand for knowledge for expert practice. Because expertise is gained in the context of practice, expertise cannot be achieved out of context or taught as an academic exercise. A clear picture of the practice of expert nurses is necessary so that those in the profession can know and articulate expert practice and direct it to the community.

Clinical Competence↗

Classification of mild Alzheimer's disease by artificial neural network analysis of SPET data.

An evaluation of the performance of artificial neural networks (ANNs) for the classification of probable Alzheimer's disease (pAD) patients was undertaken using data extracted from four regions of interest constructed on single photon emission tomographic (SPET) cerebral perfusion images. Two studies using feed-forward neural networks (FFNNs) were undertaken. The first was to determine if it would be possible to classify pAD patients and normal subjects in a mixed group, comprising 29 patients diagnosed as having pAD varying in severity from mild, established dementia to moderate dementia and 10 healthy control subjects. The second was to determine if the networks generated in the first study could prospectively classify 15 additional patients with very mild or mild cognitive impairment. The results were compared to those obtained using the same data and discriminant analysis. The relative performances of the two analysis techniques were assessed on the basis of the area under receiver operating characteristics (ROC) curves. The FFNN successfully classified all datasets in the first study, achieving an area under the ROC curve of 1.00, whereas discriminant analysis achieved 0.94. When tested on data from the second group, the areas under the ROC curves varied between 0.86 and 1.00 for the FFNN, whereas that for discriminant analysis was 0.99. We conclude that FFNNs can accurately classify pAD patients with mild to moderate dementia using data obtained from SPET cerebral perfusion images.

Aged↗

Control of the amount of free molecular iodine in iodine germicides.

Horseradish peroxidase has been used to generate iodine compositions that comprised principally free molecular iodine. The concentration of free molecular iodine in these enzyme-based compositions ranged from 44 to 63% of the thiosulphate titratable iodine; this is substantially higher than the corresponding value for the povidone-iodine preparation betadine. The biocidal efficacy of these compositions was proportional to the concentration of free molecular iodine. Iodine compositions with relatively low total iodine concentrations but high levels of free molecular iodine (20-175 ppm) killed Staphylococcus aureus and spores of Bacillus subtilis more rapidly than betadine. The effects of normal saline and these enzyme-based iodine compositions on the rate of epidermal regeneration in superficial swine wounds were comparable. These results suggest that an effective germicide containing a high level of molecular iodine need not be irritating or toxic.

Animals↗

Correlation of peak systolic velocity and angiographic measurement of carotid stenosis revisited.

BACKGROUND AND PURPOSE: Recent observations from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) questioned the reliability of peak systolic velocity (PSV) criteria for grading carotid stenosis. We compared PSV and angiographic measurements at our center together with known physiological relationships to investigate the accuracy of ultrasound. METHODS: Consecutive patients who underwent both color-coded duplex ultrasound and intra-arterial digital subtraction angiography were studied. PSV was determined with angle correction at the site of the tightest internal carotid artery narrowing. Carotid stenosis was measured on angiograms with the North American (N) and common carotid (C) methods. Variables for the stepwise multiple linear regression analysis were selected from an axisymmetrical flow model. RESULTS: Eighty bifurcations were imaged in 40 patients. PSV did not exceed 140 cm/s in normal vessels. In diseased arteries, PSV increased proportionally with increasing stenosis and decreased to 0 cm/s at occlusion. In stepwise selection of polynomial terms, the linear, quadratic, and cubic correlations of .38, .17, and .22 for N and .45, .24, and .03 for C were found to be significant (P < .02). When only stenosed vessels were evaluated, PSV increase was found with greater scatter for the N measurement: r2 = .73 for N and r2 = .85 for C (n = 50; P = .03 for the difference between two correlated correlation coefficients). CONCLUSIONS: At our laboratory PSV consistently correlates well with N and C angiographic measurements, as determined with a simple flow model. The complex nature of these correlations and greater variability of the N measurement should be taken into account when data from different centers are compared.

Angiography, Digital Subtraction↗

The clinical advantages of autologous transfusion. A randomized, controlled study after knee replacement.

We have carried out a randomised, controlled trial on 70 patients having unilateral total knee replacement in which transfusion was either with homologous bank blood or by reinfusion of unwashed blood salvaged after operation. No complications or adverse effects were observed from reinfusion. The need for bank blood was reduced by 86% in the reinfusion group but, more importantly, the number of infective episodes was significantly less when the use of bank blood was avoided. The mean length of stay in hospital was also reduced by more than two days.

Blood Transfusion, Autologous↗

Issues in patient compliance.

Patient compliance refers to the willingness and ability of an individual to follow health-related advice, to take medication as prescribed, to attend scheduled clinic appointments and to complete recommended investigations. It is a major health issue, with outcomes related to levels of morbidity, mortality and cost utilisation. Poor compliance has been reported as the most common cause of nonresponse to medication, with evidence to show that patients who adhere to treatment recommendations have better health outcomes than those who do not adhere, even when taking a placebo. Evidence-based practice guidelines, founded on clinical, behavioural and educational concepts, provide a means of measuring outcomes related to health status, patient satisfaction and cost-benefit issues, and may help to ensure that responsibility for compliance is shared between the clinician and the patient.

Humans↗

Importance of cerebral blood flow to the recognition of and physiological responses to hypoglycemia.

During hypoglycemia, cerebral blood flow (CBF) does not increase significantly until peripheral glucose levels are very low (2.0 mmol/l), that is, well below the blood glucose threshold for impairment of cognitive function (3.0 mmol/l). Because increased rates of cerebral blood flow will increase glucose transport, a failure of flow to rise earlier, before brain function is threatened, might be considered maladaptive. To examine the influence of inducing an earlier rise in CBF during hypoglycemia, eight healthy volunteers participated in three studies using a randomized, placebo-controlled design. In all three studies, a hyperinsulinemic (60 mU x m2 x min(-1)) clamp was used to maintain blood glucose levels at 4.5 mmol/l for 60 min. Thereafter, for EUG-ACZ, blood glucose was maintained at 4.5 mmol/l from 60 to 170 min and at 90 min from the start of this study, and 1-g acetazolamide i.v. was given to induce an early rise in CBF; for HYPO-ACZ, glucose was lowered over 20 min to 2.8 mmol/l and kept at that level for 90 min, and acetazolamide was given 90 min from the start of this study; and for HYPO-CON, glucose was treated as in HYPO-ACZ, and matching placebo was given in place of acetazolamide. Injection of acetazolamide was associated with a 30% rise in right (95% CI 24-34%) and left (20-32%) middle cerebral artery velocity (an index of CBF) during euglycemia without any change in hypoglycemia awareness or counterregulatory hormone levels. When glucose was lowered to 2.8 mmol/l, acetazolamide caused a similar rise in middle cerebral artery velocity in the HYPO-ACZ study. However, all subjects were less "aware" of hypoglycemia, had fewer adrenergic symptoms (sweating, palpitations, tremors; all P < 0.05), and had lower plasma epinephrine levels (1,026 vs. 1,790 pmol/l; -764 [437 to 1,097] pmol/l, point estimate of difference [95% CI]; P < 0.001), compared with the HYPO-CON study, whereas levels of other counter-regulatory hormones and norepinephrine were similar. Cognitive function (latency of the P300 evoked response) was unaffected by increasing CBF. In conclusion, enhanced rates of cerebral blood flow at the onset of systemic hypoglycemia are associated with diminished perception of low blood glucose levels and attenuation of the epinephrine counterregulatory response. These findings suggest that augmenting cerebral blood flow leads to an enhanced rate of substrate delivery to the central nervous system.

Acetazolamide↗

The early experience of a voluntary small group insurance program utilizing managed care plans.

HealthCare Group of Arizona (HCGA), a state-sponsored, voluntary health insurance purchasing program offering prepaid health plans to small businesses, became operational in 1988. This article summarizes the results from a wide-ranging evaluation of that program and discusses their implications. In general, enrollees were satisfied with their experience in their plans. HCGA did not appear to attract an adverse mix of health risks, and service utilization rates were consistent with HMO industry averages. However, these findings varied across health plans and the marketing approaches they adopted. Enrollment growth in HCGA has been steady, but premium subsidies may be necessary if HCGA is to substantially increase its enrollment of low-wage, uninsured workers.

Adolescent↗

Preparing the next generation of clinicians to manage information.

Curriculum development in informatics must be underpinned by knowledge of the information environment new recruits encounter after qualification. A pilot study was carried out to identify the type of information handling tasks newly qualified healthcare professionals are expected to undertake. This data was related to the skills junior staff possess at the point of entry to hospital posts. Data was collected on the opportunities these recently qualified individuals had to acquire IT skills and generic competence in information handling in their prequalification courses. Self-report data was supplemented by direct observation of junior staff on the wards. In addition to investigating the perspective of the junior staff, the study also explored the attitudes and expectations of senior clinicians, educationalists and NHS trust staff. The purpose of the study was to provide guidance to those involved in developing informatics curricula for clinical students at the prequalification stage. This paper reports some of our preliminary findings.

Adult↗

A brief overview of the initial location decisions of immigrants.

"The current longitudinal survey of recent migrants has provided information on the factors shaping their locational choices within Australia. The main finding is that family and friends are the dominant influence. Job opportunities are much less influential, even amongst Independent migrants."

Australia↗

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↗

A phase I trial of paclitaxel plus carboplatin in untreated patients with advanced non-small cell lung cancer.

This Phase I study was designed to determine the maximally tolerated doses of paclitaxel (given as an outpatient 3-h infusion) plus carboplatin in advanced, untreated non-small cell lung cancer. Secondary objectives were to determine the response rate, response duration, and survival. Fifty-six patients were accrued, and all were evaluable for toxicity; 50 patients were assessable for response. Paclitaxel doses ranged from 135-250 mg/m2, whereas carboplatin dosing started at 250 mg/m2 and was escalated to 400 mg/m2. Patients received therapy on day 1 every 21 days for a maximum of six cycles. Prophylactic granulocyte colony-stimulating factor was not given initially but was allowed if grade 4 neutropenia developed. Neutropenia was the major toxicity observed (41% of patients; 16% of courses) and was dose related. However, febrile neutropenia was uncommon (4%), and no patient receiving growth factor developed subsequent grade 4 neutropenia. Only one patient developed grade 4 thrombocytopenia. No grade 4 neuropathy or grade 3 or 4 myalgias/arthralgias were reported. Grade 4 allergic reactions occurred in three patients (5%), and two patients sustained grade 4 cardiac toxicity (4%). Partial responses were observed in 13 of 50 patients (26%). One of 13 patients (8%) receiving paclitaxel at 135 mg/m2 and carboplatin (250-350 mg/m2) responded versus 12 of 37 patients (32%) receiving paclitaxel doses >/= 175 mg/m2 with carboplatin doses of 350-400 mg/m2. The median time to progression, median survival, and 1-year survival rates seemed to be dose related, with median times to progression of 6, 18, and 27 weeks; median survival of 13, 29, and 39 weeks; and 1-year survival rates of 15, 28, and 41% for the 135, 175-200, and 225-250 mg/m2 groups. We conclude that full doses of both paclitaxel and carboplatin can be given safely on an outpatient basis with 3-h paclitaxel infusions. Neutropenia is the most common toxicity; response rates and survival at higher dose levels were encouraging. Phase III trials to determine the optimal dose and infusion schedule of this combination are warranted, as are trials to compare paclitaxel/carboplatin to other active single agents or combination regimens.

Adult↗