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Biomedical subjects

E Andrews

Publications and source records attributed to E Andrews.

At least 19 recordsLinked to original sources
PubMed2002

Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.

Cell Adhesion↗
PubMed2000

Evaluation of a problem-based learning workshop using pre- and post-test objective structured clinical examinations and standardized patients.

BACKGROUND: Osteoporosis is a health care issue in which family physicians play a major role. Although awareness of osteoporosis is high, recent studies suggest that application of recent advances in its treatment to the clinical setting may be low. We have developed a problem-based learning intervention for osteoporosis in which paired rheumatologists and family physicians developed nine problem-solving clinical scenarios. An educational matrix was used to link specific case scenarios with individual teaching objectives, developed via a previous needs assessment. Family physicians participated in the workshop, developing best practice responses to the clinical scenarios with a trained facilitator and content expert. METHODS: To assess the impact of this intervention, family physicians participated in a pre- and post-test evaluation, using objective structured clinical examinations and standardized patients. Objective structured clinical examination stations tested knowledge, skills, and judgment relating to osteoporosis with respect to risk factors, use of appropriate investigations including bone mineral densitometry (BMD), strategies for the prevention of osteoporosis (both pharmacologic and nonpharmacologic), treatment options for established osteoporosis (bisphosphonates and hormone replacement therapy), and management of recent osteoporosis fracture. Participants were evaluated using a predetermined score generated by their responses to objective structured clinical examinations and standardized patients (max. score = 101). Evaluations were conducted anonymously, although participants had access to their own pre- and post-test results for personal feedback. The impact of the workshop was assessed by comparing pre- and post-test responses by group, by individual, and by station. RESULTS: Participants demonstrated a significant improvement in their post-workshop scores. Of 40 participants, 26 showed improvement in score (> +10), 13 showed modest change (+1 to +10), and 1 showed a marked decrease (> -10). The greatest improvements were seen in the management of the male osteoporosis patient, determination of risk factors for osteoporosis, and the use and interpretation of bone mineral densitometry. Family physicians reported general satisfaction with the content and format of both the workshop and the evaluation process. IMPLICATIONS: We conclude that this type of problem-based learning intervention workshop results in improved knowledge, skills, and judgment in the management of osteoporosis by family physicians as objectively assessed using a pre- and post-test format including objective structured clinical examinations and standardized patients.

Clinical Competence↗
PubMed2000

Frequent exposure of mice to crude Brucella abortus proteins down-regulates immune response.

Mice repeatedly immunized via the intraperitoneal route with a Brucella abortus antigen lost their ability to develop a strong in vitro lymphoproliferative response. This result correlates with a decreased tendency of the lymphoid population to produce interferon-gamma when stimulated in culture with the immunizing antigen. With respect to the humoral response, as the number of immunizations increased, the animals produced more specific immunoglobulin M and immunoglobulin G1 antibodies. It is postulated that the long-term exposure of an animal to Brucella antigen changes the nature of the immune response from a T-cell-mediated response to a humoral response favouring the establishment of the disease.

Animals↗
PubMed2000

Concentration and composition of atmospheric aerosols from the 1995 SEAVS experiment and a review of the closure between chemical and gravimetric measurements.

We summarize the results from the various measurements and the inter-sampler comparisons from Southeastern Aerosol and Visibility Study (SEAVS), a study with one of its objectives to test for closure among chemical, gravimetric and optical measurements of atmospheric aerosol particles. Sulfate and organics are the dominant components of the SEAVS fine particles (nominally, particles with aerodynamic diameter < or = 2.5 microns) but between 28 and 42% (range over various samplers) of the gravimetrically measured total fine particle concentration is unidentified by the chemical measurements. Estimates of water associated with inorganic components and measurement imprecision do not totally explain the observed difference between gravimetric and chemical measurements. We examine the theoretical and empirical basis for assumptions commonly made in the published literature to extrapolate total fine particle concentration on the basis of chemical measurements of ions, carbon and elements. We then explore the more general question of closure using the SEAVS data as well as data from other, similar studies reported in the literature. In so combining the SEAVS measurements with other similar studies, we find a strong association between organic carbon and the unidentified component, that is, the fraction of the total fine particle concentration not identified by chemical measurements. We offer several tenable hypotheses for the relationship between the organic and unidentified components that deserve to be tested in future work. Specifically, we hypothesize that (1) errors in the sampling and analysis of organic carbon; (2) estimates of organic mass from measurements of organic carbon; and/or (3) water absorption by organics may all contribute to the observed relationship.

Aerosols↗
PubMed1999

Collision or collaboration? School-based health services meet managed care.

Describes interactions of for-profit managed-care organizations (MCOs) with not-for-profit school mental health programs that are affiliated with school-based health centers (SB-HCs). Discussion focuses on the developments and challenges that emerged between SBHCs and MCOs. While relations between MCOs and more traditional forms of mental health services (e.g., community mental health centers) are becoming established, such relations with SBHCs remain far from established. The example of the pathway Connecticut has taken in the continuing dialogue between SBHCs and MCOs is described in detail. Attention is given to the advocacy groups for child and adolescent mental health that were instrumental in convincing legislatures to enact safeguards to maintain SBHCs as providers of health and mental health care in the era of managed care. Challenges and recommendations are outlined to insure that the mental health needs of underserved, disadvantaged children are met through the provision of school-based mental health services.

Adolescent↗
PubMed1999

Vaccination with live Escherichia coli expressing Brucella abortus Cu/Zn superoxide dismutase protects mice against virulent B. abortus.

Vaccination of mice with Escherichia coli expressing Brucella Cu/Zn superoxide dismutase (SOD) [E. coli(pBSSOD)] induced a significant level of protection against virulent Brucella abortus challenge, although this level was not as high as the one reached with B. abortus vaccine strain RB51. In addition, vaccination with E. coli(pBSSOD) induced antibodies to Cu/Zn SOD and a strong proliferative response of splenocytes when stimulated in vitro with a thioredoxin-Cu/Zn SOD fusion protein.

Animals↗
PubMed1999

Initial experience with breast reconstruction using the transverse rectus abdominis myocutaneous flap: a study of 45 patients.

Breast conserving surgery for breast cancer has led to an increased interest in reconstruction following mastectomy. The transverse rectus abdominis myocutaneous flap has been proven to give good results in terms of restoration of body symmetry with near normal contour and consistency. Furthermore, immediate reconstruction has the advantage of a single procedure with less psychological morbidity, and reduction in hospital stay and overall complication rate. The aim of this study was to review our experience with the transverse rectus abdominis myocutaneous flap procedure an initial series of 45 patients. The overall complication rate of 27% is similar to that reported in the literature, with no total flap loss and nine patients with partial flap loss. There was no delay in commencement of adjuvant chemotherapy or radiotherapy and we believe our ability to detect local recurrence has not been compromised. We consider that immediate breast reconstruction is now an integral part of the surgical treatment of breast cancer.

Adult↗
PubMed1999

Case studies in osteoporosis: a problem based learning intervention for family physicians.

OBJECTIVE: To develop and evaluate a practice based small group (PBSG) learning intervention on osteoporosis for primary care physicians. METHODS: A needs assessment on osteoporosis was performed and objectives for a continuing medical education (CME) program developed by an interdisciplinary advisory committee. Nine clinical cases were developed for evaluation by CME participants with a trained facilitator and content expert using the PBSG format. The effect of the CME intervention was evaluated using a pre and post-test consisting of objective structured clinical examination stations and standardized patients. RESULTS: Fifty-four family physicians participated in 4 pilot PBSG learning sessions. The program format, content, and participant satisfaction was highly rated (> 3.35:4.0). Participants expected the program to have a significant effect on the practices (3:40:4.0). Ninety-eight percent of participants improved their pretest scores, with a mean increase of 13% (range 1-36%). CONCLUSION: Based on our experience, we advocate the use of PBSG learning interventions as an effective and acceptable method of providing CME by rheumatologists for their family physician colleagues. This format appears to be associated with a significant effect on knowledge, skills, and behavior as assessed by our study.

Aged↗
PubMed1997

Birth outcomes following zidovudine exposure in pregnant women: the Antiretroviral Pregnancy Registry.

Potential risk of adverse birth outcomes associated with the use of antiretrovirals in human immunodeficiency virus (HIV)-infected women during pregnancy must be assessed. Data through June 1995 are reported from the worldwide Antiretroviral Pregnancy Registry on the incidence of structural birth defects following prenatal exposure to zidovudine. Healthcare professionals register pregnant women anonymously. Follow-up is at time of delivery. Results are reviewed semi-annually by an advisory committee, which follows the Centers for Disease Control and Prevention (CDC) guidelines for definitions of birth defects. From 1989 through to 30 June, 1995, 198 outcomes involving exposure to zidovudine were reported. Of 73 first-trimester exposures, outcomes included one infant with a birth defect. Of 125 exposures in the second and third trimesters, six infants were reported with birth defects. Data on other antiretrovirals are insufficient for analysis. The Registry findings to date do not show an increase in the number of birth defects (1/63 in the first trimester, or 1.59%, 95% CI 0.083%, 9.69%) following prenatal zidovudine exposure when compared with that expected in the general population; however, the number of outcomes to date represents a sample of insufficient size for developing precise estimates regarding the teratogenic risk of zidovudine.

Abnormalities, Drug-Induced↗
PubMed1996

[Intervention of Campylobacter jejuni subsp. jejuni flagella in the adhesion to cellular cultures: bacteriological and immunological evidence].

The participation of the flagella of a virulent strain (O52) of Campylobacter jejuni subsp. jejuni in the adhesion to HEp-2 cells and their inhibition by means of homologous polyclonal antibodies, monoclonal anti-flagella antibodies and colostral natural antibodies (IgA) was studied. An aflagellated strain (T1) was used as negative control. Adhesion was observed in higher rates with O52 strain (72%) than with T1 strain (27.5%). Polyclonal, monoclonal and colostral antibodies inhibited O52 strain adhesion in more than 70% (p < 0.001). T1 strain adhesion was inhibited only by polyclonal and colostral natural antibodies. Our results suggest that the flagella of C. jejuni subsp. jejuni could participate effectively in the adhesion process. However, the inhibition of T1 strain by polyclonal and colostral antibodies suggests the existence of other binds of adhesins in the bacterial surface.

Bacterial Adhesion↗
PubMed1996

[Participation of Campylobacter jejuni flagellar epitopes in cellular adhesion].

Using a flagellated (052) and an aflagellated (T-1) strains we studied the participation of flagellar epitopes of C. jejuni in the adhesion to HEp-2 cells in vitro. Strain 052 was significantly more adherent than strain T-1. When adhesion assays were carried out with antiflagella monoclonal antibodies, strain 052 showed inhibition of their adhesive capacity that varied between 64.3 and 92.9%. With an ELISA test it was demonstrated that those monoclonal antibodies were specific and directed exclusively against flagellar epitopes of strain 052 being unreactive with strain T-1. Our results show that flagellar epitopes could participate in the adhesion process suggesting that flagella could be involved in the installation of the infectious process.

Antibodies, Monoclonal↗
PubMed1995

Clinical experience with atovaquone on a treatment investigational new drug protocol for Pneumocystis carinii pneumonia.

The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view.

AIDS-Related Opportunistic Infections↗
PubMed1994

Overexpression of human methylmalonyl CoA mutase in mice after in vivo gene transfer with asialoglycoprotein/polylysine/DNA complexes.

Methylmalonic acidemia resulting from genetic deficiency of methylmalonyl CoA mutase (MCM) is an often fatal metabolic disease. Somatic gene therapy for this disorder may require gene replacement in the liver. We describe overexpression of MCM in the liver of mice after in vivo gene delivery using asialoglycoprotein/polylysine/DNA (ASO/PL/DNA) targeted delivery to the liver of plasmids expressing recombinant MCM. After intravenous administration of the ASO/PL/DNA complex, the vector sequences are cleared from the blood with t1/2 = 2.5 min and > 95% of the vector is taken up by the liver. Vector sequences are cleared from the liver with t1/2 = 1.0-1.3 hr. MCM enzyme activity in the liver increases to levels 30-40% over baseline 6-24 hr after injection. No acute or chronic toxicity was observed. This net level of expression is likely to be therapeutic for MCM if the complex could be administered repetitively to treat acute episodes of life-threatening acidosis or establish a steady-state level of MCM activity. Repetitive administration of the ASO/PL/DNA complexes in mice was associated with formation of antibodies against asialo-orosomucoid and the asialo-orosomucoid complex but not against DNA.

Animals↗
PubMed1993

Expression of recombinant human methylmalonyl-CoA mutase: in primary mut fibroblasts and Saccharomyces cerevisiae.

Methylmalonyl-CoA mutase is an adenosylcobalamin-dependent enzyme which catalyzes isomerization of methylmalonyl-CoA to succinyl-CoA. Previous reports have described cloning and sequencing of a cDNA for human methylmalonyl-CoA mutase. This clone does not express an active apoenzyme after gene transfer into primary MCM-deficient fibroblasts and contains several sequences which differ from the consensus sequence of other cDNA clones. We describe reconstruction of a functional MCM cDNA and expression of recombinant enzyme activity in primary fibroblasts and Saccharomyces cerevisiae. This consensus human MCM cDNA is capable of complementing the inherited defect in mut MMA and overexpressing an enzyme in yeast with kinetic properties indistinguishable from the enzyme in murine or human tissues.

Acyl Coenzyme A↗
PubMed1993

Record linkage to conduct an epidemiologic study on the association of rheumatoid arthritis and lymphoma in the Province of Saskatchewan, Canada.

The objective of this effort was to assess the utility of the large automated database in Saskatchewan as a resource for pharmacoepidemiologic studies. To this end a study was undertaken to test the hypothesis that rheumatoid arthritis (RA) increases the risk of cancer, especially lymphoma. This was done by performing a retrospective cohort study based on record linkage data from Saskatchewan Health. From hospital discharge diagnoses in the hospital file an exposed group (RA) and two comparison groups matched to the RA group by age and sex were identified: (1) the RA group consisted of people with a discharge diagnosis of rheumatoid arthritis; (2) the osteoarthritis (OA) group consisted of people with OA discharge diagnoses; and (3) a comparison (CN) group consisted of hospitalized people with no discharge diagnoses of arthritis. Drug exposures were determined by linkage with the Prescription Drug File, cancer outcomes were determined by linkage with the Cancer Foundation file, and length of eligibility in the health plan and demographics information were determined by linkage with the registration file. The data were checked for quality of linkages across files and consistency with study definitions. Of 13,333 identified subjects, 2.8% were excluded because of apparent incorrect assignment to study group or age group or because of ineligibility in health plan during the study period. In order to decrease the possibility of misclassification of exposure (rheumatoid arthritis), hospital discharge diagnoses were used to exclude subjects with any inflammatory rheumatic diseases (IRD) from the CN (7.8%) and OA (8.3%) groups and subjects with IRD other than rheumatoid arthritis (4.6%) from the RA group. To decrease selection bias, those who had cancer within 1 year of enrollment (to exclude those in hospital because of symptoms of undiagnosed cancer) were excluded. Because RA subjects hospitalized by a rheumatologist were most likely to have valid rheumatoid arthritis diagnoses, each analysis was run twice: once with the entire RA group (N = 1210) and once with those in the RA group who were rheumatologist-hospitalized (N = 646). Logistic regression of incidence was used to control for age, sex, and use of individual disease-modifying anti-rheumatoid drugs (DMARDs). For the rheumatologist-hospitalized RA group compared to the CN group, a significant 4-fold greater risk for lymphoma/myeloma was detected when DMARD use was not controlled for, and a 3.4-fold increase in risk was detected even when use of individual DMARDs was controlled for.(ABSTRACT TRUNCATED AT 400 WORDS)

Arthritis, Rheumatoid↗