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Biomedical subjects

C Evans

Publications and source records attributed to C Evans.

At least 91 records · Page 5Linked to original sources

Interleukin-2-induces development of denditric cells from cord blood CD34+ cells.

Dendritic cells (DC) have been shown to develop along a myeloid or lymphoid lineage of differentiation propagated from bone marrow or early thymic precursor cells with hematopoietic cytokines. In our study, we have induced growth and differentiation of DC from cord blood CD34+ cells initiated in interleukin-2 (IL-2) alone or in IL-2 + stem cell factor (SCF) + tumor necrosis factor alpha (TNF-alpha)-supplemented medium and cultured with IL-2 or IL-2 + SCF for 28-35 days. Dendritic morphology and antigenic phenotype of DC grown with IL-2 were characteristic for DC cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Growth and differentiation of DC was followed by an increase in expression of MHC II and co-stimulating molecules CD80 and CD86. We have also shown the expression of the IL-2 receptor (IL-2R) gamma-chain in CD34+ cells after 2-3 days of culture with IL-2 alone. The co-expression of the IL-2R alpha, beta, and gamma subunits in both DC cultured with IL-2- or GM-CSF-containing cocktail of cytokines was also shown. The time curve for induction of IL-2R demonstrated low levels of subunit expression at the beginning of culture. The number of CD1a cells co-expressing CD25, CD122, and CDgamma increased to about 24-68 and to 78-95% after 21 and 28-35 days, respectively. Development of natural killer cells was shown along with DC. The proportion of CD56+ cells and cytotoxicity increased in a time-dependent manner.

Antigens, CD↗

Bone mineral density, collagen type 1 alpha 1 genotypes and bone turnover in premenopausal women with diabetes mellitus.

Osteopenia is a recognised complication of diabetes mellitus which could be due to abnormal bone turnover or disturbances in the calcium/parathyroid hormone/vitamin D axis or both. Genetic factors also play an important part in determining bone mass although this has not been studied in diabetes. Recently a polymorphism of the collagen type 1 alpha 1 (COL1A1) gene has been shown to be associated with low bone mass in British women. To identify subjects with diabetes who may be at risk of developing osteoporosis and fractures, we analysed bone mineral density in relation to the biochemical markers of bone turnover, calcium homeostasis and the COL1A1 genotype in a group of premenopausal women with Type I (insulin-dependent) diabetes mellitus (n = 31), Type II (non-insulin dependent) diabetes mellitus (n = 21) and control subjects (n = 20). Bone mineral density was lower at the femoral neck in the subjects with Type I diabetes (p = 0.08) as were serum 25-hydroxyvitamin D compared with control subjects (p = 0.023) and this was negatively correlated with serum collagen type 1 C-terminal propeptide (r = -0.56, p < 0.001). Bone mineral density in Type II diabetes was not different from control subjects, after correction for body mass index. Bone resorption was, however, raised in the Type II diabetic subjects as reflected by the higher urinary deoxypyridinoline values (p = 0.016) and lower collagen type 1 C-terminal propeptide:deoxypyridinoline ratio (p = 0.04). In the whole group studied, subjects with the COL1A1 's' genotype had lower bone mineral density at the femoral neck (p = 0.01) which was partly attributable to a lower body mass index. Following multiple regression analysis body mass index and collagen type 1 C-terminal propeptide concentrations remained determinants of bone mass at all three sites, whereas genotype appeared to be a predictor of bone mass at the femoral neck only. We conclude that measurement of these variables could prove useful in firstly identifying those diabetic women at risk of osteoporosis and secondly guiding therapeutic intervention.

Adult↗

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease.

Incidence of end-stage renal disease in medically treated patients with severe bilateral atherosclerotic renovascular disease. Atherosclerotic renovascular disease is an important cause of end-stage renal disease (ESRD). The exact incidence of ESRD and the rate of decline in glomerular filtration rate (GFR) in patients with this condition is unknown. We report the mortality, the rate of decline in renal function, and incidence of ESRD in 51 patients with bilateral atherosclerotic renovascular disease followed-up for a median period of 52 months. None of these patients had undergone any surgical or radiological intervention. Renal function was determined by serial measurements of serum creatinine. Bilateral atherosclerotic renovascular disease was associated with a high mortality rate; the crude mortality rate at 60 months was 45%. Assessment of renal function showed impaired renal function at time of angiography and a nonuniform and variable decline in renal function during the period of observation. The median GFR decreased from 39 mL/min (range, 15 to 80 mL/min) at time of angiography to 31 mL/min (range, 10 to 70 mL/min) and 24 mL/min (range, 10 to 40 mL/min) at 24 and 60 months, respectively (P < 0.05). The calculated mean rate of decline in GFR for all patients was 4 mL/min/yr (range, 1 to 16 mL/min/yr). Over the 5 years, there was a progressive increase in the incidence of ESRD. Of the original 51 patients who underwent angiography, six patients reached ESRD. The crude incidence of ESRD was, therefore, 12%. Patients who reached ESRD were characterized by advanced azotemia at the time of angiography (median GFR, 25 mL/min) and a rapid decline in GFR (8 mL/min) compared with patients who did not reach ESRD during the observation period (median GFR, 43 mL/min and an average rate of decline GFR of 3 mL/min).

Arteriosclerosis↗

The dean as spiritual leader.

These are hard times for medical school deans--high turnover among deans, the fiscal distress of many medical schools, the gap between what deans expect the job will be and what is required of them, the stark differences between what the job of dean is today and what it was in the past, and the threats to the academic missions of education and research. Using stories, anecdotes, and parables, the authors illustrates how these very difficulties might be an opportunity to rethink the role of deans and to re-examine the attributes and skills required of successful deans today. The ultimate goals of medical education have not changed, but the drastic nature of the changes taking place all around, and within, medical education make it more critical than ever to keep in mind what is really important. Deans must be exquisitely attuned to what is really important and they must make sure that the academic medical community never loses sight of what that is. To do that, deans must be deeply rooted personally in the enduring values and commitments that inform medicine as a profession and a vocation and in the fundamental values of medical education and scholarship; they must personify and embody these values; and they must remind us of these values and inspire us to embrace them and be guided by them. This is the sense in which deans must be "spiritual" leaders--that is, through their personal example, they must rekindle and engage the spirit of those working on behalf of the academic mission. While the need for fiscal expertise, management skills, and diplomatic and interpersonal skills in deans is widely acknowledged, the need for sensitivity to the spiritual dimensions of the work of deans has not received the attention it deserves.

Education, Medical↗

Development of the Guide to Community Preventive Services: a U.S. Public Health Service initiative.

The Task Force on Community Preventive Services is developing a Guide to Community Preventive Services (the Guide). Based on available evidence the Guide will summarize the effectiveness and cost-effectiveness of population-based interventions for prevention and control, and provide recommendations for people who plan, fund, and implement population-based services and policies. On behalf of the Department of Health and Human Services, the Centers for Disease Control and Prevention is coordinating support to the Task Force from governmental agencies, voluntary and professional groups, managed care organizations, and academia to develop and implement the Guide. Publication is targeted for the year 2000. Individual components will be published when completed.

Health Resources↗

Cost effectiveness of fluvoxamine in the treatment of recurrent depression in France.

OBJECTIVE: The objective of this study was to examine the cost effectiveness of fluvoxamine compared with tricyclic antidepressants (TCAs) in the treatment of patients with depressive episodes. DESIGN AND SETTING: A Markov process model was constructed to model the effectiveness, as measured by time without depression, and the costs of both treatments. The model examined a period of 18 months in order to capture the influence of both relapses and recurrences on the outcomes. Data for the construction of the model came from the published literature, an expert panel and a large multicentre randomised clinical trial. Costs were obtained from published sources. The setting for this study was France. MAIN OUTCOME MEASURES AND RESULTS: The results of the baseline analysis showed that the use of fluvoxamine in the maintenance treatment (recurrence prevention) of depressive disorders was less costly than TCAs with total costs (direct and indirect costs) of 40,232.40 French francs (FF) and FF52,257.53, respectively (1996 values). In addition, due to the prevention of relapse and recurrence, effectiveness favoured fluvoxamine as it was associated with a longer period of time without depression when compared with TCAs (79% of the study period vs 71%). Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: In conclusion, on the basis of the assumptions used in the model, the use of fluvoxamine as maintenance therapy is clinically and economically justified in patients with depressive disorders.

Antidepressive Agents, Second-Generation↗

Progress in development of herpes simplex virus gene vectors for treatment of rheumatoid arthritis.

Arthritis is presently incurable and poorly treatable, but there are good grounds for expecting gene therapy to improve matters considerably. Although local ex vivo delivery of anti-arthritic genes to the synovial lining of joints has shown considerable promise, intraarticular gene delivery may be desirable. Herpes simplex virus (HSV) may be a viable vector for in vivo transfer of anti-arthritic genes to joints. HSV has the advantages of high infectivity, large carrying capacity and high titer. The large packaging capacity would permit the inclusion of multiple anti-arthritic genes and necessary regulatory elements. Recombinant vectors produced by this laboratory infect synovial cells efficiently, permitting prolonged expression of transgenes in vitro and in vivo without evidence of cytotoxicity. Further improvements to this vector system include taking advantage of an endogenous HSV 'stealthing' gene, ICP47, which interferes with formation of antigen-class I complexes. Inclusion of inducible promoters to appropriately regulate expression of anti-arthritic genes should further improve this system.

Journal Article↗

In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy.

OBJECTIVE: This study explored the therapeutic effect of interleukin-1 receptor antagonist (IL-1Ra), administered by gene transfer, on the progression of osteoarthritic (OA) lesions in an experimental dog model. METHODS: Seventeen mature mongrel dogs were divided into 3 groups. Group 1 (n = 7) had an anterior cruciate ligament (ACL) section of the right knee through a stab wound incision. Groups 2 and 3 (n = 5 per group), had an ACL section of the right knee and partial synovectomy of the left knee. Each dog's synovium was subjected to enzymatic digestion, and the synovial fibroblasts were propagated in monolayer culture. Synovial cells from each dog were transduced in vitro using the retrovirus MFG with either the Escherichia coli beta-galactosidase (lac Z) gene (group 2) or the human IL-1Ra gene (group 3). Two days after surgery, the dogs received intraarticular injections as follows: group 1 phosphate buffered saline (PBS) (2 ml); group 2 autologous cells (60 x 10(6) cells/2 ml of PBS) transduced with the lac Z gene; group 3 autologous cells transduced with the IL-1Ra gene. Synovial fluid was aspirated at 2 weeks and 4 weeks. All dogs were euthanized at 4 weeks postsurgery. The right knees were dissected, and lesions were scored for macroscopic and microscopic changes. Synovial explants were dissected and representative specimens were used for histology or were cultured for 48 hours. The levels of IL-1Ra in synovial fluid and synovial explant conditioned medium were measured by specific enzyme-linked immunosorbent assay. RESULTS: The level of IL-1Ra in synovial fluid of group 3 was 202.8 +/- 131.5 ng/ml (mean +/- SEM) at 2 weeks and 2.8 +/- 2.2 ng/ml at 4 weeks after surgery. Membrane explants isolated from dogs that received synovial cells transduced with the IL-1Ra gene (group 3) actively produced IL-1Ra (4.0 +/- 2.0 ng/gm of tissue wet weight). The severity of OA cartilage lesions was similar in groups 1 and 2. In contrast, group 3 dogs had a marked reduction in macroscopic lesion severity on the tibial plateaus (P < 0.01 for grade; P < 0.04 for size) and femoral condyles. Moreover, the histologic lesion severity was decreased on both plateaus (P < 0.06) and condyles. CONCLUSION: This study showed that a local increase in IL-1Ra production in OA knee joints by intraarticular injection of transduced synovial cells can reduce the progression of experimentally induced lesions.

Animals↗

The High-Resolution FTIR Spectrum of Jet-Cooled CH3CF2Cl

The infrared spectrum of HCFC-142b, CH3CF2Cl, has been recorded at high and low resolution using a supersonic jet-FTIR spectrometer system. Molecular parameters for a number of vibrational states have been obtained from rovibrational analyses of the C-type bands nu14 (1192 cm-1) and nu15 (967 cm-1), the A-type band nu7 (905 cm-1), and the B-type bands nu5 (1234 cm-1) and nu7 + nu11 (1215 cm-1). A rotational temperature of ca. 50 K in the jet expansion has been estimated from a comparison of the experimental spectrum with band simulations calculated using the resultant molecular constants. Copyright 1997Academic Press

Journal Article↗

Detection of intra- and cross-cultural non-equivalence by simple methods in cross-cultural research: evidence from a study of eating attitudes in Nigeria and Britain.

The desiderata for cross-cultural research are reviewed showing how this is dominated by the presumption of transcultural equivalence hidden by the technical problems of translation. This model requires intensive translation work on measures to preserve "equivalence". This work can be prohibitively intensive, might lead to spurious evidence of "equivalence" and has not produced much evidence of equivalence to date. A psychometric axiom--that a measure with low reliability cannot have validity--suggests a pragmatic way to explore these issues and current statistical software and personal computers make this feasible. We recommend that all cross-cultural research should present the internal reliability of the data as this will expose all but one theoretical problem in the detection of "equivalence". We also suggest that non-equivalence may indicate cross-cultural differences in the dimensionality of eating and body image concerns rather than just a problem to be exorcised by more translation work or to be hidden by not reporting reliability. These issues are not specific to work across languages but also apply to comparisons between any social groups within cultures. This is shown using data from questionnaires in their original English with respondents who were fluent in that language.

Adult↗

Health-seeking strategies and sexual health among female sex workers in urban India: implications for research and service provision.

This paper presents and discusses selected findings from a study of health-seeking strategies in relation to sexual health among a group of female sex workers in Calcutta, India. Background information on sex work and sexually transmitted disease in Calcutta is followed by the presentation of findings pertaining to women's understandings of (sexual) health, treatment-seeking and service utilisation. In the urban context where health services are readily available, patterns of initial treatment-seeking are shown to be generally (biomedically) appropriate, but subsequent "non-compliant" therapeutic practices give cause for concern. Conventional approaches to the study of "health-seeking behaviour" are reviewed in the light of these findings and questions raised about the appropriateness of approaches that focus on initial choice of treatment type and/or assume processes of health-seeking to be determined primarily by cultural "beliefs" about illness. Inherent biomedical and culturalist biases in the orientation of such research are shown to produce an analytic neglect of the dual influences of material life conditions and people's perceptions of health, rather than illness, upon health-related strategies. Recommendations are made for operational research and policy formulation on the provision of effective sexual health services, and implications are drawn for the scope of interventions and applied research directed at improving sexual health.

Adult↗

Amphotericin B lipid complex (ABLC) for the treatment of confirmed or presumed fungal infections in immunocompromised patients with hematologic malignancies.

Sixty-four adult patients (median age 43) with hematologic malignancies who were immunocompromised after allogeneic (n = 23) or autologous (n = 9) blood/marrow transplantation, or chemotherapy (n = 32) received 68 courses of amphotericin B lipid complex (ABLC, Abelcet) at the daily dose of 5 mg/kg for presumed (n = 52) or proven (n = 16) fungal infection. The major indications for ABLC were failure of previous antifungal therapy and/or renal dysfunction. Fifty-three treatment courses in 49 patients comprising 4-58 doses (median 10) were considered evaluable. Fourteen courses administered for confirmed infections resulted in nine complete and one partial responses, and four failures (71% response). Thirty-nine empiric courses resulted in 18 complete and six partial responses, and 14 failures (64% response). The overall response rate was 66%. Five of seven evaluable patients with aspergillus pneumonia responded. Response rates were comparable for chemotherapy, autograft and allograft recipients. The change in serum creatinine from the beginning to the end of therapy was -284 to +277 mumol/l (median +24). The creatinine doubled during seven evaluable courses of therapy, five of which were associated with concomitant nephrotoxic therapy. Nephrotoxicity was comparable for transplant and chemotherapy patients. Renal dysfunction necessitated discontinuation of ABLC in only four patients. These data suggest that ABLC is effective in presumed or confirmed fungal infections in immunocompromised patients after transplantation or chemotherapy.

Adolescent↗

Drug abuse in pregnancy: obstetric and neonatal problems. Ten years' experience.

Drug abuse is an increasing problem and approximately 80% of female drug abusers are of childbearing age. This retrospective case note study reviews 10 years' experience of the management of pregnant drug abusers (n = 57) in the obstetric hospital of a London teaching hospital. Surprisingly, in view of other reports of high morbidity, no significantly increased rates of obstetric and neonatal problems were found when this group was compared with case-matched controls. Thirty-nine per cent of drug abusers managed to reduce and stop their drug use. However, 56% of the infants of drug abusers had withdrawal symptoms. Concern for her unborn child can motivate the pregnant drug abuser to comply with treatment and thus improve the outcome of pregnancy.

Journal Article↗

The use of consensus methods and expert panels in pharmacoeconomic studies. Practical applications and methodological shortcomings.

The use of expert opinion in pharmacoeconomic studies is widespread. A review of the relevant literature has shown that expert opinion is frequently used in decision analysis, Markov models and disease management, with estimates of potential values derived from Delphi panels, modified Delphi panels and expert round tables. These consensus-gathering methods are often applied as if potential drawbacks to their application were absent. This article reviews and summarises the use of these techniques in pharmacoeconomic research and evaluates the potential shortcomings of the methodology employed. In particular, several areas of concern are noted: the provision of baseline information or seed algorithms to panellists, the high attrition rate of panels, the criteria for selecting experts and the definition of consensus. This article offers recommendations for the future application of these techniques and concludes that expert opinion can still play a valuable role in pharmacoeconomic research.

Consensus Statements as Topic↗

Coronary artery disease in diabetic patients with lower-extremity arterial disease: disease characteristics and survival. A report from the Coronary Artery Surgery Study (CASS) registry.

OBJECTIVE: Patients who have diabetes and lower-extremity arterial disease (LEAD) are at an increased risk of dying from coronary artery disease (CAD). This study was undertaken to: 1) define the clinical and arteriographic factors associated with LEAD among diabetic patients; 2) determine the long-term survival and predictors of mortality of diabetic patients with LEAD, compared to those without LEAD; and 3) determine if the presence of LEAD is an independent risk factor for mortality among diabetic patients with CAD. RESEARCH DESIGN AND METHODS: A total of 263 diabetic patients from the Coronary Artery Surgery Study (CASS) registry with LEAD, who were > or = 50 years of age, and who had arteriographically proven CAD, were identified and followed for a mean of 12.8 years. A total of 1,349 comparably aged diabetic patients from the CASS registry with CAD and no evidence of LEAD were followed for an equivalent period of time. RESULTS: Compared with diabetic patients without LEAD, diabetic patients with LEAD were characterized by the presence of cerebrovascular disease, a high rate of current smoking, elevated systolic blood pressure, high grades of angina pectoris, and digitalis use. Severity of epicardial CAD and extent of CAD were not independent predictors of the presence of LEAD. On follow-up, diabetic patients with LEAD had significantly higher mortality (mostly cardiovascular) than diabetic patients without LEAD, with a median survival of 8.1 and 10.9 years, respectively. On multivariate analysis, age, the number of significantly narrowed coronary arteries, and the presence of left ventricular dysfunction predicted mortality in both subsets of diabetic patients. Among all the diabetic patients with CAD, the presence of LEAD was an independent risk factor for mortality. CONCLUSIONS: Diabetic patients with LEAD have a higher mortality rate (mostly cardiovascular) than diabetic patients without LEAD, despite no apparent anatomic differences in the severity and extent of CAD. This suggests that factors associated with the presence of LEAD, other than the anatomy of the coronary circulation, may play a role in determining survival among diabetic patients with LEAD and CAD.

Aged↗