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Biomedical subjects

J C Edwards

Publications and source records attributed to J C Edwards.

At least 109 records · Page 6Linked to original sources
PubMed1992

Induced hypothermia in the management of refractory low cardiac output states following cardiac surgery in infants and children.

Post-operative low cardiac output states remain a major cause of mortality following cardiac surgery in infants and children. Since 1979 we have used moderate induced whole-body hypothermia in the management of low-output states refractory to conventional modes of therapy. This is based not only upon the relationship between body temperature and oxygen consumption, but also on experimental work showing a beneficial effect of cooling upon myocardial contractility, particularly when there is pre-existing impairment of ventricular function. Between July 1986 and June 1990, 20 children with refractory low-output states were cooled by means of a thermostatically controlled water blanket to a rectal temperature of 32-33 degrees C. The median age was 12 months (1 week-11 years) with a median weight of 6 kg (3.5-33 kg). Ten children survived to leave hospital while a further two made a haemodynamic recovery. There was a marked reduction in heart rate (P < 0.001). The mean arterial pressure rose (P = 0.037) while there was a fall in mean atrial pressure (P < 0.001). There was a significant improvement in the urine output (P = 0.002). A fall in the platelet count (P < 0.001) was not accompanied by any change in the white cell count (P = 0.15). Although it is impossible to say whether cooling influenced the outcome in any of these children, it was usually effective in stabilising their clinical condition. The technique is simple and has a sound theoretical basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output, Low↗
PubMed1992

Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.

Blood Transfusion↗
PubMed1992

A comparison of the performance of two types of infusion device.

The delivery performance of two types of infusion pump, the IVAC 711 series syringe driver and the IVAC 531 series drop-counter, was examined by measuring the output of 16 pumps. We found that despite careful attention to the setting up of all apparatus, the IVAC 711 series syringe drivers had a significant lag phase before output matched the set rate, and that this lag phase was more pronounced at low rates of infusion. This was not the case with the IVAC 531 series which delivered the set rate from the outset. We suggest, that when the timing and rate of an infusion of drug is important from the outset and when these types of pump are being used, that either the syringe driver pump is primed by a brief period of high rate infusion vented by a three-way tap or that a drop-counter pump is used.

Infusion Pumps↗
PubMed1992

Conditional immortalization of bicarbonate-secreting intercalated cells from rabbit.

We have derived an immortalized cell line from primary cultures of bicarbonate-secreting intercalated cells from rabbit. Cells were transfected with a plasmid encoding a temperature-sensitive large T antigen of SV40 plus the neomycin resistance gene under the control of an SV40 promoter. Transfectants were selected for resistance to G418. One stably transfected clone, designated IC250, was subcloned to ensure clonality, and a subclone (clone C) was characterized in detail. The cells divide continuously at permissive temperature. At restrictive temperature, they cease dividing and assume morphological and transport properties of true bicarbonate-secreting intercalated cells. They express appropriate ultrastructural features, bind peanut lectin in an apical pattern, are rich in carbonic anhydrase, stain for proton-adenosinetriphosphatase in a basolateral pattern, and do not stain with antibodies to erythrocyte band 3. Most monolayers of transformed type B intercalated cells do not achieve a significant transepithelial resistance; those monolayers that are sufficiently electrically tight for electrophysiological studies are capable of chloride-dependent bicarbonate transport.

Adenosine Triphosphatases↗
PubMed1992

A multicentre survey of serum calcium levels in patients with malignant diseases.

Serum calcium and albumin levels were measured in 255 patients with a confirmed diagnosis of malignant disease. The average serum calcium and albumin levels were similar to those reported in an earlier larger American survey. Only 6/255 patients were above the normal range of corrected serum calcium and one patient was sufficiently hypercalcaemic (corrected serum calcium at least 2.8 mmol/L) to be included in a trial of oral clodronate therapy. The incidence of hypercalcaemia in this survey is considerably lower than that reported in the published literature (5-10%). A much larger proportion of patients (21/255) were hypocalcaemic. Serum albumin was depressed in 25/255 cases and elevated in 2/255 cases.

Calcium↗
PubMed1991

Binding of antibodies raised against tumour necrosis factor alpha (TNF alpha) to blood vessels and macrophages in inflamed synovial tissue.

The distribution of tumour necrosis factor alpha (TNF alpha) in rheumatoid synovium has been investigated. Ten rheumatoid synovia were compared with seven normal synovia and a range of other tissues, using one polyclonal and six monoclonal antibodies. A common staining pattern was obtained with five reagents. Absence of staining of tissue with the other reagents may relate to binding to different epitopes. Excluding cross-reactivity with smooth muscle seen with two reagents, results with the first five reagents were as follows. Normal tissues showed either no staining or faint staining of venular endothelium. In addition skin keratinocytes and colonic mucus showed staining. Rheumatoid synovium showed staining of venules and weaker staining of mononuclear cells, both as individual cells in the deep tissue and more uniformly in areas of the lining layer. The majority of cells that stained for TNF alpha double-stained for CD68 (macrophages). These represented less than 10% of CD68-positive cells. Isolated cells staining for TNF alpha stained for CD3 (T-cells), forming less than 1% of the total T-cells. The presence of staining of venular endothelium suggests that the cytokine may be synthesised by endothelial cells or may be taken up after production by macrophages.

Adult↗
PubMed1991

Demonstration of lymphatics in human synovial tissue.

Using a cocktail of monoclonal antibodies PAL-E and DE-U-10 (anti-desmin), combined in double labelling techniques with the lectin Ulex europaeus agglutinin I (UEAI), vessels consistent with lymphatics were demonstrated in normal human synovial tissue. These vessels were negative for the monoclonal cocktail and positive for UEAI, were thin-walled and were located close to deep arterioles and venules as expected. Elastin was not found to assist identification of lymphatics in synovium. In rheumatoid arthritic synovium no vessels staining in the manner of normal lymphatics were found. This may indicate absence or change of phenotype of this type of endothelium in disease.

Adolescent↗
PubMed1991

IL-1 alpha inhibits lymphocyte migration into a site of chronic inflammation.

The effects of murine recombinant IL-1 alpha (muIL-1 alpha) on lymphocyte migration in the mouse have been investigated. Continuous infusion of muIL-1 alpha had marked effects on patterns of lymphocyte migration into a site of chronic inflammation, inflammatory exudate and spleen; the numbers of lymphocytes migrating to the inflamed tissue and spleen were reduced in a dose-dependent manner. The number of lymphocytes in the blood of muIL-1 alpha-treated animals was increased in a dose-related manner. The decrease in numbers of lymphocytes present in the chronically inflamed site may either be due to a direct inhibitory action of muIL-1 alpha or reflect an increased rate of cell migration through the inflamed tissues accompanied by a more rapid return to the circulation. These findings suggest that IL-1 alpha may act not only as an inflammatory cytokine, but also as a modulator with anti-inflammatory activity during chronic inflammation.

Animals↗
PubMed1991

Current practices in admission interviews at U.S. medical schools.

Although the interview is widely used in the selection of applicants for admission to U.S. medical schools, little is known about current interview practices. The authors formulated a 46-item questionnaire concerning the interview process for medical school applicants, then in 1989 sent it to admission officials at all the 127 LCME-accredited schools in the United States. The questionnaire concerned the interview's status as a predictor; interviewers and interview structure; interviewer training; and the utility of interview data. Seventy-two percent of those sent the questionnaire completed and returned it. The responding admission officials indicated that the interview had two major purposes at their schools: as a means of assessing candidates' noncognitive skills and as a public relations tool. Most schools' interview processes were loosely to moderately structured, and interviewers received minimal training. It is concluded that the interview's role is primarily subjective and that it has a definite but imprecise influence on admission decisions.

Education, Medical, Undergraduate↗
PubMed1991

A comparative study of the cellular, exudative and histological responses to carrageenan, dextran and zymosan in the mouse.

A murine 6-day air-pouch model of inflammation has been developed and used to compare the patterns of acute and chronic inflammatory response to three irritants, carrageenan, dextran and zymosan, each injected into the cavity of the pre-formed pouch. The inflammation was assessed by measurement of exudate volume and numbers of infiltrating leucocytes over a 30-day time course. Histological changes in the inflamed air-pouch lining tissue were also investigated. The inflammatory response to carrageenan was acute with moderate exudate formation and cell numbers. Dextran produced a mild inflammatory reaction with low cell infiltration into exudate. In contrast, the inflammatory response to zymosan was greater in terms of cell migration, but smaller in terms of exudate volume and occurred later in the time course. Histological changes in the inflamed air-pouch tissue were also markedly different in response to the three irritants. Carrageenan induced a rapid, mainly polymorphonuclear leucocyte (PMN) infiltrate into the tissue and deposition of fibrin on the luminal surface. The response to dextran was characterized by a rapid resolution of the inflammatory response, with fewer leucocytes present in the lining and no fibrin deposition. In contrast, zymosan caused a marked but slower leucocyte influx, with greater numbers of monocytes, and clearance of the zymosan particles from the air-pouch lining by macrophages. This study indicates that by using different irritants to produce inflammation, it may be possible to dissect the roles played by various cells and inflammatory mediators during acute and chronic inflammation.

Animals↗
PubMed1991

Morphological localization of hyaluronan in normal and diseased synovium.

The morphological distribution of hyaluronan in normal and diseased synovium has been determined using a probe derived from the hyaluronan binding region of cartilage proteoglycan core protein. Normal synovium showed hyaluronan surrounding the lining layer cells with little in deeper layers. Rheumatoid synovium showed intense staining for hyaluronan throughout the tissue, notably associated with blood vessels and areas of dense cellular infiltration. Osteoarthritic tissues varied according to the degree of infiltration present, with inflamed specimens closely resembling rheumatoid tissue. The distribution of hyaluronan in diseased synovium suggests a role in aspects of the inflammatory process such as angiogenesis and cell traffic.

Adult↗
PubMed1990

Terminal N-acetylglucosamine in chronic synovitis.

The distribution of terminal GlcNAc residues in normal and diseased synovial tissue has been studied using a mouse monoclonal antibody (mAb) which binds to terminal N-acetylglucosamine (GlcNAc). Normal human connective tissue, including synovium, showed no staining for terminal GlcNAc. Normal epithelial tissues, including tonsillar epithelium, skin, small intestinal epithelium and salivary epithelium showed cellular staining. Synovium from patients with definite rheumatoid arthritis showed dense granular staining of macrophages. In addition, synovium from 9 of 12 patients with definite rheumatoid arthritis showed reticular extracellular staining indicating deposition of material bearing terminal GlcNAc in the connective tissue stroma. The extracellular staining was not seen in synovium from patients with osteoarthritis. Extracellular material bearing terminal GlcNAc may act as an inflammatory stimulus in rheumatoid arthritis, either by acting as antigen or by interaction with receptors on macrophage membranes which also recognize GlcNAc on bacterial material, thus triggering biochemical pathways normally occurring in response to the presence of micro-organisms.

Acetylglucosamine↗
PubMed1990

Immunohistological reassessment of accessory cell populations in normal and diseased human synovium.

Accessory cell populations in normal and diseased synovial tissue have been reanalyzed following the development of the monoclonal antibody, EBM11, directed against the CD68 epitope which is expressed by macrophages in all locations so far examined. Previous studies used as a macrophage marker the monoclonal antibody RFD7 which binds only a proportion of (mature) macrophages. Using double indirect immunofluorescence, normal and rheumatoid synovial samples were examined for the presence of cells which bind the putative dendritic cell marker, RFD1, in conjunction with either RFD7 or EBM11. RFD1 positive cells were found in five of 40 normal synovia. Of these cells, 30-35% were negative for RFD7 or EBM11 and, when closely apposed to T-lymphocytes, showed a typical interdigitating morphology. In contrast, all of ten rheumatoid synovia contained RFD1 positive cells; the extent of double labelling with macrophage markers varied with the position of the cells in the tissue. As expected, EBM11 stained a larger number of cells with macrophage morphology than RFD7. The combination of RFD1 and EBM11 appears to be a useful method for identifying interdigitating dendritic cells in connective tissue, these cells being characterized by positive RFD1 and negative EBM11 binding. On this criterion, interdigitating dendritic cells were plentiful in rheumatoid synovium and present, albeit infrequently, in normal synovium.

Antibodies, Monoclonal↗
PubMed1990

The interview in the admission process.

Significant demographic, legal, and educational developments during the last ten years have led medical schools to review critically their selection procedures. A critical component of this review is the selection interview, since it is an integral part of most admission processes; however, some question its value. Interviews serve four purposes: information gathering, decision making, verification of application data, and recruitment. The first and last of these merit special attention. The interview enables an admission committee to gather information about a candidate that would be difficult or impossible to obtain by any other means yet is readily evaluated in an interview. Given the recent decline in numbers of applicants to and interest in medical school, many schools are paying closer attention to the interview as a powerful recruiting tool. Interviews can be unstructured, semistructured, or structured. Structuring involves analyzing what makes a medical student successful, standardizing the questions for all applicants, providing sample answers for evaluating responses, and using panel interviews (several interviewers simultaneously with one applicant). Reliability and validity of results increase with the degree of structuring. Studies of interviewers show that they are often biased in terms of the rating tendencies (for instance, leniency or severity) and in terms of an applicant's sex, race, appearance, similarity to the interviewer, and contrast to other applicants). Training interviewers may reduce such bias. Admission committees should weigh the purposes of interviewing differently for various types of candidates, develop structured or semistructured interviews focusing on nonacademic criteria, and train the interviewers.

Bias↗
PubMed1990

T gamma delta cells and their subsets in blood and synovial tissue from rheumatoid arthritis patients.

We have examined the frequencies of T gamma delta cells in blood, synovial fluids, and synovial membranes of patients with rheumatoid arthritis (RA) and in blood from age-matched controls. Immunocytochemical and immunohistochemical techniques were used with monoclonal antibodies BB3 and A13 to define a major and minor blood subset of T gamma delta cells respectively. Together, these antibodies identify the majority (if not all) of the peripheral blood T gamma delta cells. Significantly lower levels of T gamma delta cells were found in the blood of RA patients compared with controls, whilst higher but not significant numbers were found in the synovial fluids of paired samples. Scattered T gamma delta cells were found only in some synovial membranes with a distribution similar to the T alpha beta cells. Analysis of the two different T gamma delta-cell subsets indicated a ratio of BB3 to A13 of about 5:1 in control and RA blood. However, this ratio was less than 1:1 in the RA synovial fluids and membranes. The migratory nature of the A13+ cells could account for their predominance in these sites. The possible pathological significance of these cells in the rheumatoid synovial fluid and synovial membranes is discussed.

Adult↗
PubMed1990

The prevalence and distribution of macrophages bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in synovium.

Fc-receptors for IgG (Fc gamma R) are important triggers of effector function in macrophages. We have investigated the distribution of cells bearing Fc gamma R I, Fc gamma R II, and Fc gamma R III in 14 synovia and 3 nodules from rheumatoid arthritis (RA) patients, using monoclonal antibodies on serial cryostat sections. 8 osteoarthritis (OA), 2 ankylosing spondylitis (AS) patients and one sarcoid patient were also studied. Significant numbers of macrophages bearing Fc gamma R were present in inflamed synovial tissue with no significant difference in relative frequency between RA and OA. There was no correlation with the degree of lymphocytic infiltration. Distinctive staining patterns for the three Fc-receptors suggest differential regulation of these molecules on macrophages in synovium.

Antigens, Differentiation↗