An unusual case of recurrent septicaemia.
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Bacteremia↗
Biomedical subjects
D Cole
Publications and source records attributed to D Cole.
Specific cytolytic T-cell responses to human CEA from patients immunized with recombinant avipox-CEA vaccine.
Avipox viruses are replication-defective members of the poxvirus family. Avipox-derived vectors such as ALVAC (canarypox) and fowlpox have the ability to infect mammalian cells, including human cells, but do not replicate. The first clinical trial of an avipox recombinant vaccine for patients with advanced carcinomas has recently been conducted using the ALVAC vector and the human carcinoembryonic antigen (CEA) transgene (designated ALVAC-CEA; J. L. Marshall et al, J. Clin. Oncol., 17: 332-337, 1999). The T-cell responses elicited by patients before and after vaccination with the ALVAC-CEA recombinants are characterized in this report. Pre- and postvaccination peripheral blood mononuclear cells (PMBCs) of the eight patients positive for HLA-class I A2 allele, were incubated with the HLA-A2-CEA peptide CAP-1 and interleukin 2. In no cases using prevaccination PMBCs could cultures be established that had the ability to lyse C1R-A2 target cells pulsed with the CAP-1 peptide. However, T-cell cultures from seven of eight of these same patients, obtained from PBMCs after ALVAC-CEA vaccination, were shown to lyse C1R-A2 cells only when pulsed with CAP-1. Moreover, all seven of these T-cell cultures were shown to lyse allogeneic human carcinoma cell lines (SW1463 and SW480) that were both A2+ and expressed CEA; an allogeneic tumor cell line (LS174T) expressing CEA that was negative for A2 expression was not lysed. HLA-A2+ and CEA+ autologous tumor cells were also capable of being lysed by CEA-specific T cells from this patient. Analysis of this CTL line also revealed the expression of several homing and adhesion-associated molecules. Fluorescence-activated cell sorter analysis of the T-cell lines established from patients after ALVAC-CEA vaccination revealed that most were CD8+/CD4-, but many also had a CD8+/CD4+ component. Analyses of T-cell receptor Vbeta usage of several of the CEA-specific CTL lines showed a relatively diverse Vbeta pattern. These studies demonstrate for the first time the ability to vaccinate cancer patients with an avipox recombinant and derive T cells that are capable of lysing allogeneic and autologous tumor cells in a MHC-restricted manner. These studies thus form the rationale to use such replication-deficient recombinant vaccines in future cancer vaccine trials.
Antigen-Presenting Cells↗
Lessons learned--15 years of the WHO-NCTB: a review.
Based on expert recommendations, the World Health Organization (WHO) recommended the Neurobehavioral Core Test Battery (NCTB) in 1983 to detect neurotoxicity in world-wide populations. The NCTB consists of 7 neurobehavioral tests (Digit Symbol, Digit Span, Benton visual memory test/recognition form, Santa Ana dexterity test, Simple Reaction Time, Pursuit Aiming II, and Profile of Mood States). Research with the NCTB provides the context for the results of a mini-symposium held in 1999 to discuss the lessons learned about using the NCTB in working populations. Speakers from Africa, Asia, Europe, and North America reviewed data from 94 studies using the NCTB, including 63 from China, 13 from Korea, 11 from Poland, three from South Africa, three from the USA, and one from Ecuador. Although a consensus was not sought in the symposium, the key lessons learned that emerged from the various presentations, were: * The NCTB is effective in testing adults with 12 or more years of formal education, but can not reliably test persons with less than 9 years of education. * People from cultures very different from those in Europe and North America (eg, aboriginal and African cultures) may not be tested effectively by the NCTB, although others such as at least some Asian populations, can be. To address this problem, the construct validity of the NCTB should be established in a wide range of countries. * The POMS measures of emotion proved to be very sensitive to neurotoxic exposures in several countries, but the POMS was the NCTB test most affected by cultural differences. The Digit Symbol or the Milan modification of that test was also highly sensitive to neurotoxic exposures. * Examiner drift following training to administer the NCTB is a significant problem in technically trained Examiners. Pursuit Aiming II is very difficult to score reliably.
Adult↗
A world apart. Interview by Jeremy Davies.
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Administrative Personnel↗
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↗
Follow-up of breast cancer in primary care vs specialist care: results of an economic evaluation.
A randomized controlled trial (RCT) comparing primary-care-centred follow-up of breast cancer patients with the current standard practice of specialist-centred follow-up showed no increase in delay in diagnosing recurrence, and no increase in anxiety or deterioration in health-related quality of life. An economic evaluation of the two schemes of follow-up was conducted concurrent with the RCT Because the RCT found no difference in the primary clinical outcomes, a cost minimization analysis was conducted. Process measures of the quality of care such as frequency and length of visits were superior in primary care. Costs to patients and to the health service were lower in primary care. There was no difference in total costs of diagnostic tests, with particular tests being performed more frequently in primary care than in specialist care. Data are provided on the average frequency and length of visits, and frequency of diagnostic testing for breast cancer patients during the follow-up period.
Breast Neoplasms↗
An environmental radionuclide baseline study near three Canadian naval ports.
This paper summarizes an environmental radionuclide baseline study undertaken for the Department of National Defence in Canada. The purpose of the project was to establish levels of radionuclides present in the environment around areas where nuclear propelled vessels may be berthed. Specifically, this report describes environmental baselines near Halifax (Nova Scotia), Esquimalt (British Columbia), and Nanoose Bay (British Columbia). Valued ecosystem component samples were taken from dairy farms, beef producers, market gardens, vegetables, tree fruits and berries within the study areas, as well as marine bivalves (mussels and clams), salmon, seaweed, and food from native fisheries. Numerous naturally occurring isotopes were detected and quantified. The only non-naturally occurring isotope positively identified was in the form of trace quantities of 131I, measured in the Halifax study zone (attributed to local hospital cancer therapy). 137Cs is the only other anthropogenic radionuclide detected. Its origin may be the combination of fallout from the Chernobyl accident and fallout from atmospheric nuclear weapon tests. The results indicate that nuclear-powered vessels have not resulted in activity levels that would contribute a significant radiation exposure to the public, the biota, and the environment within the three study zones.
British Columbia↗
Trends in indications and outcomes in the Whipple procedure over a 40-year period.
There have been increasing changes in the role of pancreatoduodenectomy (PD) in the management of benign and malignant pancreatic disease. The aim of this paper was to compare the current role of PD with that of our earlier experience. The records of patients undergoing PD at our institution between 1983 and 1996 (Group A) were reviewed and compared with cases between 1956 and 1982 (Group B). Student's t test was used to analyze differences between groups. A total of 153 PDs were performed with 98 (64%) in Group A (88% of these in the last 6 years) and 55 (36%) in Group B. Carcinoma of the head of the pancreas was the most common indication for surgery in both periods (43% and 47% for Groups A and B, respectively). In Group A, the next most common indication was chronic pancreatitis, accounting for 28 per cent versus 13 per cent in Group B. Carcinoma of ampulla of Vater was also a common indication, making up 21 per cent of the cases in Group A and 20 per cent in Group B. Preoperative biliary drainage was performed in 62 per cent of Group A and 3 per cent of Group B patients (P < 0.001). Postoperative complications were comparable in both groups: delayed gastric emptying (22%), wound infection (17%), pancreatic fistula (13%), gastrointestinal bleeding (8%), and intestinal obstruction (3%). The perioperative mortality rate was significantly different between the two groups: 1 per cent in Group A versus 16 per cent in Group B (P < 0.001). Mean postoperative length of stay was 17 days in Group A (22 days for benign disease) and 25 days for Group B (P < 0.01). In the last 40 years, there has been a rise in the use of PD for chronic pancreatitis and a significant decrease in postoperative mortality and hospital length of stay. These data support the safety of PD in the management of patients with both benign and malignant periampullary disease.
Adult↗
Comparison of breast cancer patient satisfaction with follow-up in primary care versus specialist care: results from a randomized controlled trial.
BACKGROUND: Routine follow-up of breast cancer patients in specialist clinics is standard practice in most countries. Follow-up involves regularly scheduled breast cancer check-ups during the disease-free period. The aims of follow-up are to detect breast cancer recurrence and to provide psychosocial support to the patient; however, little is known about patients' views on breast cancer follow-up. AIM: To assess the effect on patient satisfaction of transferring primary responsibility for follow-up of women with breast cancer in remission from hospital outpatient clinics to general practice. METHOD: Randomized controlled trial with 18 months' follow-up in which women received routine follow-up either in hospital outpatient clinics or from their own general practitioner. Two hundred and ninety-six women with breast cancer in remission receiving regular follow-up care at two district general hospitals in England were included in the study. Patient satisfaction was measured by means of a self-administered questionnaire supplied three times during the 18-month study period. RESULTS: The general practice group selected responses indicating greater satisfaction than did the hospital group on virtually every question. Furthermore, in the general practice group there was a significant increase in satisfaction over baseline; a similar significant increase in satisfaction over baseline was not found in the hospital group. CONCLUSION: Patients with breast cancer were more satisfied with follow-up in general practice than in hospital outpatient departments. When discussing follow-up with breast cancer patients, they should be provided with complete and accurate information about the goals, expectations, and limitations of the follow-up programme so that they can make an informed choice.
Ambulatory Care↗
Characterization of glucose transport activity reconstituted from heart and other tissues.
We examined several aspects of glucose transport reconstituted in liposomes, with emphasis on transporters of rat heart (mostly GLUT4) compared to those of human erythrocytes (GLUT1), and on effects of agents that modulate transport in intact cells. Several types of samples gave higher reconstituted activity using liposomes of egg lipids rather than soybean lipids. Diacylglycerol, proposed to activate transporters directly as part of the mechanism of insulin action, increased the intrinsic activity of heart transporters by only 25%, but increased the size of the reconstituted liposomes by 90%. The dipeptide Cbz-Gly-Phe-NH2 inhibited GLUT4 with a Ki of 0.2 mM, compared to 2.5 mM for GLUT1, which explains its preferential inhibition of insulin-stimulated glucose transport in adipocytes. Verapamil, which inhibits insulin- and hypoxia-stimulated glucose transport in muscle, had no effect on reconstituted transporters. Heart transporters had a higher Km for glucose uptake (13.4) than did GLUT1 (1.6 mM), in agreement with a recent study of GLUT1 and GLUT4 expressed in yeast and reconstituted in liposomes. Transporters reconstituted from heart and adipocytes were 40-70% inactivated by external trypsin, suggesting the presence of trypsin-sensitive sites on the cytoplasmic domain of GLUT4. NaCl and KCl both reduced reconstituted transport activity, but KCl had a much smaller effect on the size of the liposomes.
Animals↗
Preventing disability from work-related low-back pain. New evidence gives new hope--if we can just get all the players onside.
Despite the publication in the mid-1990s of comprehensive practice guidelines for the management of acute low-back pain, both in the United States and elsewhere, this ubiquitous health problem continues to be the main cause of workers' compensation claims in much of the Western world. This paper represents a synthesis of the intervention studies published in the last 4 years and is based on a new approach to categorizing these studies that emphasizes the stage or phase of back pain at the time of intervention and the site or agent of the intervention. Current thinking suggests that medical management in the first 3-4 weeks after the onset of pain should be generally conservative. Several studies of rather heterogeneous interventions focusing on return to work and implemented in the subacute stage (3-4 to 12 weeks after the onset of pain) have shown important reductions in time lost from work (by 30% to 50%). There is substantial evidence indicating that employers who promptly offer appropriately modified duties can reduce time lost per episode of back pain by at least 30%, with frequent spin-off effects on the incidence of new back-pain claims as well. Finally, newer studies of guidelines-based approaches to back pain in the workplace suggest that a combination of all these approaches, in a coordinated workplace-linked care system, can achieve a reduction of 50% in time lost due to back pain, at no extra cost and, in some settings, with significant savings.
Absenteeism↗
Socioeconomic and environmental covariates of premature mortality in Ontario.
This paper contributes to debates on the broad determinants of health and on the policy shift from curative to preventive and protective interventions. It addresses empirically the relative importance of influences on health with a multiple regression analysis of ecologic data from the 49 counties of Ontario. One model achieved high predictive power (that is, Adj R2 > 75%, p < 0.0001). Educational levels were a strong predictor of population health, showing a consistent inverse relationship with premature mortality ratios for both sexes and it was the strongest predictor for females. A low income variable supplied the strongest prediction for male mortality. This variable displayed a positive association with male mortality. Municipal expenditures on environmental protection exerted a negative effect on male mortality. These findings raise questions about the current directions of health policy in Ontario where the provincial government has reduced funding to social and environmental programs, while promising to maintain health care funding.
Adolescent↗
Outpatient laparoscopic surgery.
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Adult↗
The value of communication through the use of a newsletter.
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Communication↗
Bayesian interim statistical analysis of randomised trials: the case against.
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Angiotensin-Converting Enzyme Inhibitors↗
Doxorubicin-induced acute changes in cytotoxic aldehydes, antioxidant status and cardiac function in the rat.
Doxorubicin (DOX)-induced cardiotoxicity is thought to be caused by free radical-mediated mechanisms. An in vivo rat model was developed to investigate the DOX-induced cascade of early biochemical changes focusing on the central role of the aldehydic lipid peroxidation products. Antioxidant status was evaluated by glutathione measurements. Creatine Kinase (CK) activity was measured as an index of cardiac injury. Development of functional abnormalities were documented by echocardiography. The results showed that aldehydes in rat plasma and heart tissues increased significantly following DOX treatment. The changes occurred early, peaked around 2 h after DOX administration, and the levels declined or returned to baseline value within 8-24 h. Toxic aldehyde levels including malondialdehyde, hexanal and 4-hydroxy-non-2-enal also increased. Acyloin levels, metabolic products of aldehydes, increased early and then decreased in plasma, and there was a significant decrease in heart tissues after DOX treatment. GSH levels decreased early, then increased by 24 h, while GSSG levels decreased initially, then increased after DOX treatment, suggesting early depletion of GSH and a later rebound phenomenon. CK levels were elevated after treatment. The functional abnormalities were documented by stress echocardiography in some rats although the changes were not consistent at such an early stage following treatment. Our data confirmed the involvement of free radicals, and suggested that the cytotoxic aldehydes play a central role in initiating the steps that lead to functional impairment of the myocardium following DOX administration. Scavengers and the metabolic removal of some of the aldehydes also play a role in protecting the myocardium against injury.
Aldehydes↗
A multicenter, double-blind comparison of the effects of nefazodone and fluoxetine on sleep architecture and quality of sleep in depressed outpatients.
This study was an 8-week, randomized, double-blind, parallel-group investigation that compared the effects of nefazodone and fluoxetine on sleep architecture and on clinician- and patient-rated sleep measures in 43 outpatients with moderate to severe, nonpsychotic major depressive disorder and insomnia. Twenty-two patients received nefazodone 200 mg daily for 1 week, followed by 400 mg daily for 7 weeks. Twenty-one patients received fluoxetine 20 mg daily. Dosage increases (to 500 mg/day for nefazodone and 40 mg/day for fluoxetine) were available after day 29, depending on clinician judgement. Sleep parameters were measured during baseline phase, while patients were unmeasured and symptomatic, and at weeks 2, 4, and 8 of treatment. Nefazodone and fluoxetine were equally effective as antidepressants. However, compared with baseline, nefazodone increased sleep efficiency and reduced the number of awakenings and percent awake and movement time, whereas fluoxetine increased the number of awakenings and did not significantly alter sleep efficiency or percent awake and movement time. Although fluoxetine increased stage 1 sleep and rapid eye movement (REM) latency and reduced total percent REM sleep, nefazodone increased REM sleep, decreased REM latency, and did not alter stage 1 sleep. Differences between treatment groups, based on change from baseline, revealed greater sleep efficiency, fewer awakenings, less percent awake and movement time, less percent stage 1 and more REM sleep, and shorter REM latency for nefazodone compared with fluoxetine. Significantly greater improvement in clinician- and patient-rated sleep disturbance was found with nefazodone compared with fluoxetine. Nefazodone was associated with better sleep quality.
Adult↗