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Biomedical subjects

C Evans

Publications and source records attributed to C Evans.

At least 73 records · Page 4Linked to original sources

Relative cost of autologous red cell salvage versus allogeneic red cell transfusion during abdominal aortic aneurysm repair.

The costs of washed autologous red cell concentrate obtained by intraoperative red cell salvage were compared to the costs of allogeneic packed red cell transfusion during 110 consecutive abdominal aortic aneurysm repairs. The mean volume of scavenged blood during elective procedures was 1350 ml (range 350 to 6675 ml, n = 90) and emergency procedures 2750 ml (range 750 to 9400 ml, n = 20). The mean volume of processed (washed) blood returned during elective repairs was 759 ml (range 150 to 2900 ml, n = 51) and emergency repairs 1117 ml (range 0 to 4100 ml, n = 20). During elective repairs, the cost of routine autologous red cell salvage ($151 per 285 ml unit) was only slightly greater than the estimated cost of cross-matched, leucocyte-reduced, allogeneic blood ($143 per 285 ml unit). During emergency repairs, washed autologous red cells ($83 per 285 ml unit) were less expensive than allogeneic packed red cells. These findings indicate that, compared with the use of allogeneic packed red cells, red cell salvage during emergency abdominal aortic aneurysm repair can be justified on an economic basis alone, and that routine red cell salvage during elective repair can achieve the benefits of autologous blood at little extra cost to the community.

Aged↗

Measurement and psychotherapy. Evidence-based practice and practice-based evidence.

BACKGROUND: Measurement is the foundation of evidence-based practice. Advances in measurement procedures should extend to psychotherapy practice. AIMS: To review the developments in measurement relevant to psychotherapy. METHOD: Domains reviewed are: (a) interventions; (b) case formulation; (c) treatment integrity; (d) performance (including adherence, competence and skillfulness); (e) treatment definitions; (f) therapeutic alliance; and (g) routine outcome measurement. RESULTS: Modern methods of measurement can support 'evidence-based practice' for psychological treatments. They also support 'practice-based evidence', a complementary paradigm to improve clinical effectiveness in routine practice via the infrastructure of Practice Research Networks (PRNs). CONCLUSIONS: Advances in measurement derived from psychotherapy research support a model of professional self-management (practice-based evidence) which is widely applicable in psychiatry and medicine.

Clinical Competence↗

Current challenges in wound care management: an overview.

This article provides an overview of the latest theories and technology in compression therapy, and the use of growth factors and skin substitutes. Compression therapy is a major factor in the treatment of venous leg ulcers and is widely used and readily available on the Drug Tariff. Skin substitute and growth factors provide a new technological approach to wound healing with hope for the future management of both acute and chronic wounds. While new technologies are an exciting prospect for the future of wound management, there can be no substitute for good wound care. In the interest of optimum wound management and patient care, health professionals have a duty to find ways to improve patients' quality of life.

Bandages↗

Expert judgement in pharmacoeconomic studies. Guidance and future use.

Research in the field of pharmacoeconomics has increased substantially during the past decade. Much of this research has been on the design and analysis of data concerning the relative merits of one drug or device compared with another in terms of costs and effects. Concomitant with these evaluations has been the development of guidelines for the conduct of economic evaluations in several countries. However, despite an increase in research, little attention has been paid to how different study designs may influence the results of a study. The use of expert judgement in decision analytic modelling is one area where design issues may influence the findings of a study. This issue is examined for the case of modified Delphi and Delphi panels. Although the use of expert opinion in modelling studies seems to be widespread, there is little consistent application, understanding or reporting of the techniques used. In particular, the definitions of techniques vary between studies, the criteria for determining when consensus is reached vary, and the reporting of these criteria is absent. Future studies using expert judgement should be more aware of the controversies surrounding the issue and provide more reporting of the techniques used. It is proposed that future validation exercises may assist researchers in determining the most appropriate application of methods.

Economics, Pharmaceutical↗

Congenital anomalies after prenatal ecstasy exposure.

Prospective follow-up of 136 babies exposed to ecstasy in utero indicated that the drug may be associated with a significantly increased risk of congenital defects (15.4% [95% CI 8.2-25.4]). Cardiovascular anomalies (26 per 1000 livebirths [3.0-90.0]) and musculoskeletal anomalies (38 per 1000 [8.0-109.0]) were predominant.

Abnormalities, Drug-Induced↗

Mouse model of a familial hypertrophic cardiomyopathy mutation in alpha-tropomyosin manifests cardiac dysfunction.

To investigate the functional consequences of a tropomyosin (TM) mutation associated with familial hypertrophic cardiomyopathy (FHC), we generated transgenic mice that express mutant alpha-TM in the adult heart. The missense mutation, which results in the substitution of asparagine for aspartic acid at amino acid position 175, occurs in a troponin T binding region of TM. S1 nuclease mapping and Western blot analyses demonstrate that increased expression of the alpha-TM 175 transgene in different lines causes a concomitant decrease in levels of endogenous alpha-TM mRNA and protein expression. In vivo physiological analyses show a severe impairment of both contractility and relaxation in hearts of the FHC mice, with a significant change in left ventricular fractional shortening. Myofilaments that contain alpha-TM 175 demonstrate an increased activation of the thin filament through enhanced Ca2+ sensitivity of steady-state force. Histological analyses show patchy areas of mild ventricular myocyte disorganization and hypertrophy, with occasional thrombi formation in the left atria. Thus, the FHC alpha-TM transgenic mouse can serve as a model system for the examination of pathological and physiological alterations imparted through aberrant TM isoforms.

Animals↗

Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer.

BACKGROUND: Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined. METHODS: Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain. RESULTS: Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population. CONCLUSIONS: Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.

Adult↗

What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey.

OBJECTIVE: To define the relations between age, sex, lower limb symptoms, and the presence of trunk varicose veins on clinical examination. DESIGN: Cross sectional population study. SETTING: 12 general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh. PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867 women) aged 18-64 selected from the computerised age-sex registers of participating practices. MAIN OUTCOME MEASURES: Self administered questionnaire on the presence of lower limb symptoms and physical examination to determine the presence and severity of varicose veins. RESULTS: Women were significantly more likely than men to report lower limb symptoms such as heaviness or tension, swelling, aching, restless legs, cramps, and itching. The prevalence of symptoms tended to increase with age in both sexes. In men, only itching was significantly related to the presence and severity of trunk varices (linear test for trend, P=0.011). In women there was a significant relation between trunk varices and the symptoms of heaviness or tension (P</=0.001), aching (P</=0.001), and itching (P</=0.005). However, the level of agreement between the presence of symptoms and trunk varices was too low to be of clinical value, especially in men. CONCLUSIONS: Even in the presence of trunk varices, most lower limb symptoms probably have a non-venous cause. Surgical extirpation of trunk varices is unlikely to ameliorate such symptoms in most patients.

Adolescent↗

Erythrocytapheresis for chronically transfused children with sickle cell disease: an effective method for maintaining a low hemoglobin S level and reducing iron overload.

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long-term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre-transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months of erythrocytapheresis, none of the patients developed complications related to the procedure or to the increased blood use. Ferritin levels decreased by a mean of 26.5% in all patients. When evaluating the ferritin level in five patients, who remained on chelation therapy with deferoxamine (DFO), the level dropped by a mean of 32%. The levels remained stable in the three patients who were not on DFO. The procedure is safe and effective in reducing iron overload and can obviate the need for chelation therapy, even when the target Hb S is maintained at the standard 30% range.

Adolescent↗

The generation of human dendritic and NK cells from hemopoietic progenitors induced by interleukin-15.

Interleukin-15 (IL-15) is a pleiotropic cytokine that induces the generation and differentiation of lymphoid cells and shares many biological activities with IL-2. We have shown here the development of dendritic cells (DC) from human CD34+ hemopoietic precursor cells cultured for 2-4 weeks with IL-15 alone. DC generated with IL-15 have typical morphological, immunocytochemical, phenotypic, and functional characteristics of mature DC. Dual flow cytometry analysis performed weekly demonstrated increasing co-expression of CD1a or CD83 with HLA-DR, CD80, CD86, IL-2R alpha, beta, and gamma. Two populations of cells were distinguished among CD34+ progeny. Small and medium-size cells were mainly natural killer (NK) cells (72.6-85.2% CD56+) and low numbers of DC (9.1-21.3% CD1a+). Large cells were mostly DC (75.4-95.4% CD1a+). Isolated CD34+ cells did not express IL-2R subunits but after 2-3 days in culture with IL-15, they were found to express IL-2Rgamma. Induced expression of IL-2Rgamma on CD34+ cells may explain the primary mechanism of IL-15-regulated differentiation of hemopoietic precursor cells. Thus, our data suggest that IL-15 stimulates CD34+ cells to differentiate into NK and DC and may represent a new growth and survival factor for lymphoid DC.

Antigens, CD34↗

Large-scale propagation of recombinant adherent cells that secrete a stable form of human glandular kallikrein, hK2.

Human glandular kallikrein 2 (hK2) is a trypsin-like serine protease that is expressed predominantly in the prostate epithelium and has 78% aa identity with prostate-specific antigen (PSA). hK2 has been recognized as a potential prostate cancer marker and has been demonstrated to be highly expressed in prostate cancer compared to benign prostatic tissue. Purification and characterization of hK2 have been impeded due to its lower expression in bodily fluids and tissues compared to PSA and its ability to autodegrade. Therefore, to study biochemical and biological characteristics of hK2, a stable and enzymatically inactive mutant form of hK2, hK2(A217V), was expressed in a hamster cell line, AV12-664 (AV12-hK2(A217V)). AV12-hK2(A217V) cells secreted prohK2(A217V) (phK2(A217V)) in the spent medium at approximately 2.5 microgram/ml. Since AV12-hK2(A217V) are adherent cells, it was necessary to develop an efficient system to propagate large numbers of cells to obtain significant quantities of phK2(A217V). In this paper, we compared ceramic core bioreactor and microcarrier beads as alternatives to static culture to propagate adherent cells. Considering production levels, ease of operation, cost effectiveness, and labor, microcarrier beads were found to be a better alternative. Our findings led to the development of a general protocol for large-scale propagation of adherent cells on microcarrier beads eliminating the need for propagating AV12-hK2(A217V) in culture flasks or bioreactors. Microcarrier beads coated with AV12-hK2(A217V) cells could be propagated in 1- or 3-liter spinner flasks and were passed from one spinner to the next in a manner analogous to static culture or could be frozen and later used as inoculum for subsequent spinners. Using this protocol, >40 liters of spent medium was harvested within 30 days, which in turn was used to purify phK2(A217V). phK2(A217V) purified from spent medium of cells grown either on microcarrier beads or in culture flasks were biochemically similar as indicated by HIC-HPLC profile followed by sequencing of relevant peaks.

Animals↗

Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis.

To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/0- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints con- tained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1beta using retrovirus transduced synovial cells, the HSV T/0- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases.

Adoptive Transfer↗

Magnitude of the disease burden from neurocysticercosis in a developing country.

Cysticercosis contributes to higher epilepsy rates in developing countries than in industrialized ones, yet no estimate exists for the associated burden of disease. We used epidemiological data on neurocysticercosis in Peru to calculate the burden of disease and applied our model to the other countries of Latin America where neurocysticercosis is endemic to determine a regional estimate. Analysis of 12 population-based community studies demonstrated that neurocysticercosis was endemic in highland areas and high jungles, with seroprevalences from 6% to 24%. In one community, the adult seizure disorder rate was 9.1% among seropositive persons versus 4. 6% among seronegative persons; we used this difference for estimates. On the basis of average prevalence rates in areas of endemicity of 6%-10%, we estimated that there are 23,512-39,186 symptomatic neurocysticercosis cases in Peru. In Latin America, an estimated 75 million persons live in areas where cysticercosis is endemic, and approximately 400,000 have symptomatic disease. Cysticercosis contributes substantially to neurological disease in Peru and in all of Latin America.

Animals↗

Development of a luminescent bioassay for thyroid stimulating antibodies.

The hyperthyroidism of Graves Disease (GD) is due to thyroid stimulating antibodies (TSAb) which are thyrotropin (TSH) agonists. They are detected routinely by measuring their ability to inhibit TSH binding to the receptor (TBII), which does not reflect their true biological activity. Current bioassays which measure cAMP by RIA, are not suitable for routine use. We have developed a luminescent bioassay for TSAb, by introducing a cAMP responsive luciferase construct into CHO cells stably expressing the human TSH receptor (TSHR). Clone lulul displays dose dependent TSH response detectable from 10 microU/ml and maximal at 10 mU/ml when a >25 fold increase in light output is obtained. 34 euthyroid sera were tested to determine a reference range, with values >1.5 relative light units (R.L.U.) being considered positive. An international TSAb standard responded in a dose dependent manner with 10 mIU/ml giving an R.L.U. of >10. The assay was adapted to a 96 well format for automatic readout and 100 treated GD samples (50 TBII negative and 50 TBII positive) were tested, 73% being positive. In contrast only 4% of 79 control sera from individuals with Hashimoto's, non-thyroid autoimmunity or multinodular goitre produced R.L.U. >1.5. When 44 of the GD sera were compared in a traditional salt-free bioassay, 61% were positive compared with 75% in the new luminescent assay. In conclusion, we have developed a luminescent bioassay for TSAb, using unfractionated serum which is capable of high throughput suitable for routine use.

Animals↗

Patient self-reports in pharmacoeconomic studies. Their use and impact on study validity.

The validity of estimates of resource utilisation based on patient recall has not been firmly established. A comprehensive literature search was conducted to identify studies that used patient self-reports to derive estimates of healthcare resource utilisation, direct nonmedical costs and indirect costs. Previous work in this area was examined to determine the issues that were most important in determining whether patient self-reports lead to valid and unbiased estimates in cost-effectiveness studies. This study reviews and highlights areas where patient self-reports lead to reliable estimates and where their use may lead to erroneous conclusions. In particular, it is noted that patient recall of resource utilisation declines over time, that the salience of a treatment episode affects recall and that the perceived social acceptability of a condition and other confounding factors may influence patient reporting. Moreover, it appears that not all elements of healthcare consumption are recalled to the same degree: medication use tends to be recalled with less accuracy than hospitalisation. In terms of the potential impact on cost-effectiveness results, the main concern is with problems of validity rather than bias, although bias may occur when the results are applied to league tables.

Cost-Benefit Analysis↗