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Biomedical subjects

E G Armstrong

Publications and source records attributed to E G Armstrong.

At least 19 recordsLinked to original sources
PubMed2001

Comparing health care delivery systems--initiating a student exchange project between Europe and the United States.

BACKGROUND: Cross-cultural contact among different health care systems can provide a framework for identifying the strengths and weaknesses of one's own healthcare system. However, such contact has rarely had much impact upon medical education curricula. Despite intense debate on reforming the healthcare delivery systems (HCDS) in Europe and the United States, there is very little formal representation of this interdisciplinary field in our educational programs. DESCRIPTION: To address this problem, a medical student exchange program was conducted in which students developed case studies that produced comparative analyses of HCDS in Germany, Sweden, Denmark and the United States. Each case is intended to highlight critical differences among the systems. EVALUATION: Students and their faculty preceptors completed pre- and post-exchange questionnaires to assess perceived knowledge of the HCDS and the adequacy of time devoted to it in their curricula. Both perceived that too little attention was devoted to this content in their programs. Following the exchange, students described clear increases in perceived knowledge. DISCUSSION: Our common interest in curriculum reform was key to implementing the exchange. The written cases generated by the students are being developed as course material in some of the schools and a conference is planned to disseminate the cases and the implementation strategies for their inclusion in medical curricula.

Cross-Cultural Comparison↗
PubMed2001

"Practicing" medicine without risk: students' and educators' responses to high-fidelity patient simulation.

PURPOSE: To understand the responses of medical students and educators to high-fidelity patient simulation, a new technology allowing "practice without risk." METHOD: Pilot groups of students (n = 27) and educators (n = 33) were exposed to a simulator session, then surveyed with multiple-choice and open-ended questions. Open-ended comments were transcribed and coded. They were analyzed for recurring themes and tested for inter-rater agreement. An independent focus group subsequently performed higher-level thematic analysis. RESULTS: Overall, 85% of the students rated the session excellent and 85% of the educators rated it excellent or very good. Over 80% of both groups thought that simulator-based training should be required for all medical students. Analytic categories derived from written comments were: Overall Assessment (i.e., "generally good experience"); Process Descriptors (i.e., "very realistic"); Teaching Utility (i.e., "broad educational tool"); Pedagogic Efficacy (i.e., "promotes critical thinking"); and Goals for Future Use (i.e., "more practice sessions"). Thirty percent of students and 38% of educators were impressed by the realism of the simulator, and they (37% and 25%, respectively) identified the ability to "practice" medicine as the primary advantage of simulation. The focus group rated cost as the major current disadvantage (66%). CONCLUSIONS: Students' and educators' responses to high-fidelity patient simulation were very positive. The ability to practice without risk must be weighed against the cost of this new technology.

Attitude of Health Personnel↗
PubMed2000

Enhancing nutrition education through faculty development: from workshops to Web sites.

Faculty resistance to changing medical school curricula is a major barrier to overcome in the effort to expand nutrition education. With clinical clerkships becoming more decentralized and basic science courses utilizing more small group teaching, the problem of reform is compounded by the increasing numbers of a more dispersed teaching faculty. A faculty development program was designed to complement a thematic approach to the inclusion of nutrition in a 4-y curriculum. The program offers workshops to help faculty learn how to teach in new settings while acquiring new knowledge about nutrition. Additionally, a themes Web site offers a window that faculty may use to review current nutrition content, to plan their teaching agendas, and to continually reassess where nutrition fits in the curriculum.

Curriculum↗
PubMed1998

Equivalent recognition of free and ACT-complexed PSA in a monoclonal-polyclonal sandwich assay is conferred by binding specificity of the monoclonal antibody.

The Bayer Immuno 1 PSA Assay measures free and ACT-complexed PSA on an equimolar basis, although it uses a monoclonal antibody (MM1) for capture and polyclonal antibodies for detection. Competitive inhibition studies using antibodies directed at various epitopes on PSA and PSA-ACT demonstrated that the capture antibody, MM1, does not bind to free PSA simultaneously with antibodies against Epitope E which is exposed only in free PSA. Affinity studies showed that the affinity constants of MM1 for both free PSA and PSA-ACT are similar. One explanation for the properties of MM1 is that it precludes the binding of antibodies to Epitope E due to steric hindrance. Alternatively, the binding of MM1 causes a conformation change within the free PSA molecule, so that Epitope E is altered in a way that causes a loss of binding affinity. The unusual properties of MM1 are responsible for the equimolar response of this monoclonal-polyclonal sandwich assay for free and ACT-complexed PSA.

Alkaline Phosphatase↗
PubMed1996

Crafting cases for problem-based learning: experience in a neuroscience course.

Clinical cases for problem-based learning should capture the relevance of patient encounters, and not serve merely as a 'take-off' point for scientific study. As a vehicle of learning, the case should drive the science and the science should drive the case. Decision points elicit intellectual commitment, and help to raise the level of inquiry. Our cases are focused, avoiding clinical complexity and reliance on pattern recognition. We emphasize formulation of evidence-based mechanistic hypotheses. The case does not stand alone, but must suit its position in the course and curriculum.

Curriculum↗
PubMed1988

Incidence of early loss of pregnancy.

We studied the risk of early loss of pregnancy by collecting daily urine specimens from 221 healthy women who were attempting to conceive. Urinary concentrations of human chorionic gonadotropin (hCG) were measured for a total of 707 menstrual cycles with use of an immunoradiometric assay that is able to detect hCG levels as low as 0.01 ng per milliliter, with virtually 100 percent specificity for hCG in the presence of luteinizing hormone. Our criterion for early pregnancy--an hCG level above 0.025 ng per milliliter on three consecutive days--was determined after we compared the hCG levels in the study group with the levels in a comparable group of 28 women who had undergone sterilization by tubal ligation. We identified 198 pregnancies by an increase in the hCG level near the expected time of implantation. Of these, 22 percent ended before pregnancy was detected clinically. Most of these early pregnancy losses would not have been detectable by the less sensitive assays for hCG used in earlier studies. The total rate of pregnancy loss after implantation, including clinically recognized spontaneous abortions, was 31 percent. Most of the 40 women with unrecognized early pregnancy losses had normal fertility, since 95 percent of them subsequently became clinically pregnant within two years.

Abortion, Spontaneous↗
PubMed1988

Development of highly sensitive immunoassays to measure human chorionic gonadotropin, its beta-subunit, and beta core fragment in the urine: application to malignancies.

A variety of malignancies have been associated with the presence of human chorionic gonadotropin, hCG, its subunits, and fragments of its beta-subunit in blood and urine. The usefulness of these hCG-related tumor markers in nontrophoblastic malignancies has been inhibited by inadequate assay techniques. In order to achieve the required sensitivity and specificity, concentration steps and other procedures to remove cross-reacting human luteinizing hormone were necessary. In addition, the coexistence of a fragment of the hCG-beta or beta human luteinizing hormone subunit contributes to significant errors of measurement in urine. The importance of the hCG-beta fragment as a potential tumor marker has been recognized previously but no method was available to measure this antigen readily. We report here the development of a series of radioimmunometric, two-site assays which will accurately measure hCG, hCG-beta subunit, and the beta-subunit fragment directly in small volumes of unprocessed urine. These assays are highly specific, extremely sensitive, and not labor intensive since they employ microtiter plate procedures. Application of these assays to urine samples from patients with gynecological malignancies indicated that over 50% of all patients tested excreted the hCG-beta fragment in their urine. Also, this fragment comprised more than 50% of the moles of hCG immunoreactive components present in the specimens that were positive for hCG. This cancer marker is also demonstrable in trophoblastic malignant states such as choriocarcinoma in which the low molecular weight fragment can also be visualized directly by immunoblotting procedures. We conclude that a search for hCG immunoreactivity in the urine of patients with malignancies will be improved by the inclusion of accurate measurements of the prominent quantities of the beta fragment excreted by these individuals.

Biomarkers, Tumor↗
PubMed1988

Structure of the human chorionic gonadotropin beta-subunit fragment from pregnancy urine.

A major portion of the hCG immunoreactivity detectable in pregnancy urine is derived from a fragment of hCG beta. This lacks the COOH-terminal portion of hCG beta, but retains immunoreactivity with most antibodies raised against the beta-subunit of hCG. To improve clinical measurements of hCG and assess the importance of such fragments in human urine, we have isolated and determined the structure of this molecule. The hCG beta fragment was isolated from a partially purified commercial preparation of hCG (Organon) by gel filtration and immunoaffinity chromatography using monoclonal antibodies. It was found to consist of two polypeptide chains composed of residues beta-(6-40) disulfide-bridged to residues beta-(55-92). It also differs from the beta-subunit of hCG in its carbohydrate structure, lacking sialic acid and having a low but variable amount of galactose. A beta-fragment containing the same two NH2-terminal sequences was also isolated from a single pregnant woman's urine. The two major polypeptides comprising the beta-fragment contain a total of nine half-cystine residues, raising the possibility that a free thiol may exist or that a third undetected disulfide-bridged peptide is present in the intact fragment. However, tests for the presence of a free thiol have been negative. Another intrinsic characteristic of the beta-fragment is the formation of a variable amount of dimer in solutions of neutral pH. beta-fragment will not combine with intact alpha-subunit. Despite the absence of regions beta-(1-5), beta-(41-54), and beta-(93-145), the beta fragment is recognized by the SB-6 antibody and most monoclonal antibodies elicited to the beta-subunit, thus excluding half of the amino acids of the beta-subunit from the epitope(s) where these antibodies bind.

Amino Acid Sequence↗
PubMed1988

Preparation and characterization of antibodies to the urinary fragment of the human chorionic gonadotropin beta-subunit.

hCG is a glycoprotein hormone composed of two dissimilar subunits (alpha and beta) and is normally synthesized by trophoblastic tissue. Its measurement by immunoassay is widely employed as a test for pregnancy, but can be complicated by cross-reactivity with human (h) LH. Immunoassays based on the beta-subunit of hCG have been employed to decrease this cross-reactivity with hLH, but when these assays are used with urine specimens, the antibodies employed also detect a fragment of hCG beta, which can lead to significant differences in measurement. To overcome these problems, we have developed a series of monoclonal antibodies to the beta fragment of hCG recovered from pregnancy urine. Some of the antibodies that bind to this beta fragment are directed to a region of hCG beta that is different from the epitopes recognized by antibodies raised against the intact beta-subunit. The new epitopes available in the hCG beta fragment form the basis for novel immunoassays. These beta fragment antibodies are used in conjunction with other antibodies, directed to different epitopes of the hormone, to produce a series of immunoradiometric assays that can discriminate among intact hormone, free hCG beta, and hCG beta fragment. The hCG beta fragment antibodies described herein have affinities between 10(9) and 10(11) M-1 for the beta fragment and exhibit varying degrees of discrimination between the hCG beta fragment, the beta-subunits of hCG and hLH, and intact hCG and hLH.

Animals↗
PubMed1988

Bioimmunoassay (BIA): a sandwich immunoassay scheme employing monoclonal antibodies and hormone receptors to quantify analytes.

When some antigens bind to receptors, a portion of the antigen remains exposed and can be recognized by labeled monoclonal antibodies. By measuring the amount of antibody bound to the antigen-receptor complex, one can quantify the amount of antigen that is present. Since this assay procedure depends on simultaneous receptor recognition of a biologically active site and antibody recognition of a distal epitope on the analyte, we call it a bioimmunoassay. Bioimmunoassays have many of the advantages of radioligand receptor assays (RRA) used to quantify biological activity and, depending on the choice of antibodies employed, may be more specific than RRA. In addition, since they are sandwich assays, they are usually more sensitive than RRA. Bioimmunoassays can be performed in several different modes and in the case described here we used a radiolabeled antibody to detect hormone-receptor complexes. Hence we term this example a bio-immunoradiometric assay or BIO-IRMA. We illustrate the properties of various assay procedures using a monoclonal antibody to the beta subunit of hCG which recognizes an epitope common to all other mammalian LH/hCG-like gonadotropins and which is capable of detecting 10 pg of hCG standard. In principle, this assay can be applied to any material capable of binding to a receptor, enzyme, etc. which can also be recognized by an antibody. Since it is a sandwich type of assay, it is subject to the same advantages and limitations of other sandwich assays except that it can be used to discriminate some biologically active and inactive analytes. Monoclonal antibodies which are prepared from spleen cells of animals immunized with antigen-receptor complexes and selected for their ability to bind antigen-receptor complexes should prove most useful for bioimmunoassay procedures.

Animals↗
PubMed1987

Detection of desialylated forms of human chorionic gonadotropin.

Urinary forms of human chorionic gonadotropin (hCG) with oligosaccharides deficient in sialic acid content (ashCG) have been reported to be excreted by patients with choriocarcinoma in greater amounts than by healthy, pregnant women. Although ashCG potentially could be a useful marker for the diagnosis and management of gestational trophoblastic neoplasia, the methods previously used for its detection were not suitable for routine clinical application. Therefore, we have devised a simpler method which can provide specific and sensitive measurements of ashCG in urine. This method, which is designated as a lectin-immunoradiometric assay (LIRMA), employs an agarose-coupled lectin to selectively extract the ashCG, which is then quantified directly with a purified and radiolabelled rabbit antibody. The LIRMA has been applied to demonstrate that there is an increased excretion of ashCG by choriocarcinoma patients. It is also applicable, in principle, for the study of any glycoprotein which has a reduced content of sialic acid in its carbohydrate side chains.

Chorionic Gonadotropin↗
PubMed1987

Unique variants of hCG in sera of choriocarcinoma patients.

Human chorionic gonadotropin (hCG) of pregnancy can be separated into several variants by an isoelectric focusing (IEF) method. The hCG produced by choriocarcinoma consists of components found in pregnancy sera (pI 3.9-6.0) and, in addition, unique variants with more acidic isoelectric points ranging from 3.2 to 3.7. The sera of all five patients with advanced choriocarcinoma contained these unique acidic variants of hCG and the immunoreactive levels were significantly higher in these patients than in normal pregnant women or patients afflicted with hydatidiform mole or invasive mole. When the acidic variants of hCG were treated with neuraminidase they migrated to the alkaline region (pI 9-11) of the IEF column. In conclusion, sera of choriocarcinoma patients contain unique variants of hCG. The finding that these highly acidic components can be converted to molecules with an alkaline pI by neuraminidase digestion suggests that this high negative charge may be due to an increased sialic acid content. Patients possessing the acidic variants of hCG in their sera had poor survival rate. Determination of the variants may be useful as a prognosis marker and in evaluating the efficacy of therapy.

Chorionic Gonadotropin↗
PubMed1987

Nonreceptor binding of human chorionic gonadotropin (hCG): detection of hCG or a related molecule bound to endometrial tissue during pregnancy using labeled monoclonal antibodies that bind to exposed epitopes on the hormone.

When hCG adsorbs to surfaces, including membranes from tissues that lack specific hCG receptors, it adsorbs with a particular orientation. Some sites on the alpha- and beta-subunits project away from the surface and can be detected with radiolabeled monoclonal antibodies. Other epitopes, which are located on a region on the hormone that presumably contacts the surface, lose their ability to bind antibody. Using antibodies specific for epitopes on hCG which remain exposed and can be detected when the hormone is adsorbed to rat brain homogenates, we found hCG or closely related substances bound to progestational decidual tissues. Immunologically reactive material adsorbed to the decidual tissue increased and decreased in parallel with the serum levels of hCG throughout pregnancy. Binding of labeled monoclonal antibody to substances similar or identical to hCG in other tissues, including placenta and fetal lung, but not red cells, also was identified. Unlike material adsorbed to decidual tissues, receptor-bound hCG was not recognized by any of our alpha-subunit-specific antibodies. This finding suggests either that the adsorbed hormone has a different orientation than receptor-bound hormone or that the adsorbed hormone has dissociated into subunits. These studies represent the first detection of nonreceptor binding of hCG or related molecules to tissues lacking receptors or presumed not to synthesize the hormone. The role of nonreceptor-bound hCG, if any, is unknown. Other than its effects on stimulation of luteal steroidogenesis during early pregnancy, the role of hCG during most of pregnancy has not been determined. Conceivably, the nonreceptor binding we identified is related to a role for hCG in pregnancy that is not associated with an action on the ovarian LH receptor.

Adsorption↗
PubMed1987

The use of biochemical assays in epidemiologic studies of reproduction.

Recent progress in the assay of urinary hormones has opened new opportunities for epidemiologists to study hormones and health outcomes. This is especially true for studies of female reproduction. The cyclic nature of female reproduction can be fully described only by continuous frequent measurements that, in order to be practical, require easily collected biological specimens. We describe our experience in collecting and analyzing daily urine specimens from 301 healthy women. We conclude that this approach is not only feasible but potentially of great value to epidemiologists for studying fertility, early pregnancy, the effects of toxic exposures on reproduction, and the relationships between reproduction and later risk of chronic diseases.

Adult↗
PubMed1987

Urinary human chorionic gonadotropin among intrauterine device users: detection with a highly specific and sensitive assay.

The mechanism by which the intrauterine device (IUD) prevents clinical pregnancy has not been established. The possibility that the IUD works primarily at the time of implantation or beyond has raised legal and ethical concerns. Numerous studies have measured human chorionic gonadotropin (hCG) among IUD users as a way to determine whether implantation routinely occurs in the presence of an IUD. Both positive and negative findings have been reported, reflecting major difficulties in the measurement of hCG at low levels. In this study, we collected daily urine specimens for up to three menstrual cycles from 40 women who used nonmedicated IUDs. We assayed these urines with an immunoradiometric assay that is highly specific for hCG at very low concentrations. This assay allows us to describe patterns of hCG rise and fall that would be undetectable by standard radioimmunoassays. In this study of IUD users, we found only one incident of probable early pregnancy loss among 107 cycles. With the use of an assay sensitive to hCG at levels as low as physiologic background, the possibility of frequent unrecognized implantation among IUD users can be reasonably excluded.

Adult↗
PubMed1985

Characterization and relative orientation of epitopes for monoclonal antibodies and antisera to human chorionic gonadotropin.

We analyzed ten monoclonal antibodies and three polyclonal antisera directed against human chorionic gonadotropin by immunoassay in order to determine which pairs of antibodies are capable of binding simultaneously to hCG. A relative orientation of epitopes on the surface of hCG could be inferred from a matrix of data describing the abilities of particular antibody pairs to inhibit competitively or enhance the binding of each other. These results indicated that the binding site of each of the antibodies could be assigned to one of three different regions of the hCG molecule, and at least one antibody binding within each region exhibited a substantial preference for hCG relative to human luteinizing hormone. One of these regions is the COOH-terminal portion of the hCG beta subunit. A second region contains the binding site for the SB6 rabbit antiserum (which has been widely employed in clinical studies) as well as the binding sites of several monoclonal antibodies. Antibodies to this second region characteristically bind both the whole hormone and the free beta subunit. A third region contains the binding sites of a previously reported human antiserum and also several monoclonal antibodies. These antibodies characteristically react preferentially with the intact hormone relative to the free subunits. The information contained in the type of epitope map described here can be used as the rational basis for the design of two-site immunoradiometric assays for hCG and/or its subunits.

Animals↗
PubMed1985

Measuring early pregnancy loss: laboratory and field methods.

We intensively studied 30 women attempting pregnancy in order to lay groundwork for larger studies of early pregnancy loss. These women collected first morning urine specimens for up to 6 months after discontinuing use of birth control. Urine specimens were successfully collected for 98% of the woman-days in the study. Three assays for human chorionic gonadotropin (hCG) were performed on each urine specimen. An immunoradiometric assay (IRMA) specific to the carboxyterminal peptide of the hCG beta-chain proved to be more sensitive and more specific than two radioimmunoassays (RIAs). Using the IRMA, we found four cases in which hCG rose and fell over successive days, consistent with early pregnancy loss. For three of these four cases, the level of hCG was too low to be detectable with the RIAs. Among the control group of five women with tubal ligations, there was no detectable hCG above threshold with the IRMA. Thus, the enhanced sensitivity and specificity of the IRMA allows very early pregnancy losses to be identified that would otherwise be undetectable. Furthermore, its effectiveness with small quantities of first morning urine makes the IRMA a useful tool for epidemiologic studies.

Abortion, Spontaneous↗