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Biomedical subjects

A Whelan

Publications and source records attributed to A Whelan.

At least 55 records · Page 3Linked to original sources
PubMed1994

Human glucagon-like peptide-1 receptor gene in NIDDM. Identification and use of simple sequence repeat polymorphisms in genetic analysis.

Glucagon-like polypeptides, GLP-1-(7-36)-amide and GLP-1-(7-37), are important regulators of insulin synthesis and secretion by islet beta-cells. The hypothesis to be tested in this study was that defects in the islet beta-cell GLP-1 receptor gene contribute to the impaired glucose-regulated insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM). Human islet GLP-1 receptor genomic clones were isolated, and two highly polymorphic simple sequence repeat regions (GLP-1R-CA1 and GLP-1R-CA3) were identified. Polymerase chain reaction assays were developed to define alleles. For GLP-1R-CA1, 14 alleles were observed in African-Americans (heterozygosity [het] = 0.78) and 6 alleles in Caucasians (het = 0.67). For GLP-1R-CA3, 16 alleles were observed in African Americans (het = 0.89) and 8 alleles in Caucasians (het = 0.83). By genotyping all members of the 40 reference Centre d'Etude du Polymorphisme Humain pedigrees at GLP-1R-CA3, the human GLP-1 receptor gene was uniquely placed on chromosome 6p between GLO1 and D6S19, 20.4 cM from human leukocyte antigen. To assess the possible role of the GLP-1 receptor gene in determining the genetic susceptibility to NIDDM, allelic frequencies of GLP-1R-CA1 and GLP-1R-CA3 were compared between African-American NIDDM patients (n = 95) and control subjects (n = 93). The frequencies did not differ between the two groups at either GLP-1R-CA1 or GLP-1R-CA3. The GLP-1 receptor gene simple-sequence repeat polymorphisms were used for linkage analysis in Utah Mormon pedigrees (n = 16) with NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Serum IgA and IgG subclasses during treatment for acute respiratory exacerbation in cystic fibrosis: analysis of patients colonised with mucoid or non-mucoid strains of pseudomonas aeruginosa.

Patients with cystic fibrosis (CF) have a high prevalence of Pseudomonas aeruginosa infection which causes chronic infection of the mucosal surfaces of the lung. This results in recurrent immune stimulation and hypergammaglobulinemia. The present study examines the levels of circulating Ig classes, IgG and IgA subclasses in 13 adult patients with CF during acute pulmonary infection and post-exacerbation. Total serum IgG levels were raised in the patients during infection and post-treatment when compared to the normal range (mean +/- SEM: 17.21 +/- 1.4 g/l vs 16.45 +/- 1.5 g/l respectively; normal range 8-16 g/l). In contrast, total IgM (2.6 +/- 0.26 vs 2.69 +/- 2.74 g/l; normal range 0.6-2.8 g/l) and IgA levels (2.5 +/- 0.52 vs 2.41 +/- 0.48 g/l; normal range 0.5-4 g/l) remained unchanged when examined during all stages of the disease. Of the 13 patients studied, 69%, 39% and 31% had IgG, IgM and IgA levels respectively raised above the normal range values. The mean levels of individual IgG subclasses examined in this group of patients revealed values within the normal ranges, however IgG2 and IgG3 were increased in 31% and 46% of patients. Individual IgG3 levels fell in 77% (10/13) and IgG4 in 62% (8/13) of the patients post-exacerbation. With regard to IgA subclasses, significant reduction in the IgA1 levels were observed post treatment (3687 +/- 539 mg/l vs 2713 +/- 498 mg/l, p < 0.01). In contrast, IgA2 levels were increased from 279 +/- 49 mg/l to 421 +/- 69 mg/l, although statistical significance was not reached. Upon antibiotic treatment for infection, the findings in this study show that IgA1 which is susceptible to bacterial proteases is reduced with a concommitant increase in the protease resistant IgA2 subclass. Moreover, patients colonised with non-mucoid strains of P. aeroginosa had higher total IgA levels due to the raised IgA1 subclass whereas they had lower IgG levels due to low IgG2 and IgG4 subclasses.

Acute Disease↗
PubMed1993

IL-2 enhances polyclonal IgM but not IgM-rheumatoid factor synthesis by activated human peripheral blood B cells.

IgM-rheumatoid factor (RF) is thought to be involved in the pathogenesis of rheumatoid arthritis (RA). Several cytokines are known to regulate immunoglobulin synthesis. In this study the effects of IL-2 on polyclonal IgM and IgM RF synthesis were compared. Cytokines were added to peripheral blood B cells from normal subjects and patients with RA after activation by Staphylococcus aureus Cowan 1 (SAC). The addition of IL-2, but not IL-4 or IL-6, resulted in significant enhancement of IgM synthesis in cultures from both healthy subjects and patients with RA. Similar degrees of enhancement were seen in both peripheral blood mononuclear cell and highly purified B cell cultures. IgM-RF was synthesized after activation in cultures from healthy subjects and spontaneously in cultures from RA patients. In contrast to polyclonal IgM synthesis, IL-2 failed to augment IgM-RF synthesis in cell cultures from either healthy subjects or RA patients. This study demonstrates different effects of IL-2 on IgM and IgM-RF synthesis.

Adult↗
PubMed1993

Contrasting levels of in vitro cytokine production by rheumatoid synovial tissues demonstrating different patterns of mononuclear cell infiltration.

Synovial membrane samples obtained at knee arthroplasty from 22 patients with rheumatoid arthritis (RA) were characterized histologically. Two groups were identified. Tissue samples from 15 patients demonstrated multiple focal lymphoid aggregates of mononuclear cells (group A). Samples from the remaining seven patients demonstrated diffuse mononuclear cell infiltration (group B). Samples of each synovial membrane (0.25 g) were cultured for cytokine production. The highest levels of IL-1 beta and IL-6 were produced by group A tissues: 19.1 +/- 19.6 ng/ml IL-1 beta (mean +/- s.d.) and 264.4 +/- 301.9 ng/ml IL-6, versus 3.8 +/- 6.6 ng/ml and 54.7 +/- 42.6 ng/ml respectively. Small quantities of IL-2 and IL-4 were measured in both groups: the levels of IL-2 in group A cultures were highest (P = 0.04). Moreover, using MoAbs, the most intense cytokine staining in the tissues was detected in group A. Similar total numbers of each cell subpopulation and similar quantities of immunoglobulin and rheumatoid factor synthesis were measured in both groups. It is suggested that the presence of multiple focal lymphoid aggregates associated with higher levels of cytokine production observed in group A represent a greater degree of immunological activation, and may represent a subgroup of patients with a greater potential for articular destruction.

Adult↗
PubMed1993

Nursing staff requirements for neonatal intensive care.

A study to estimate the number of nursing staff required for neonatal nursing was undertaken. Certain nursing tasks, such as transporting any infant, caring for the dying infant, and looking after the very unstable infant required continuous attention by one nurse (5.5 whole time equivalent (wte) nurses for each cot). The stable ventilated infant required 10.5 nursing hours each day-that is, 2.4 wte/cot. Infants with intravenous infusions, but not ventilated, required only slightly less nursing time: 9.25 nursing hours each day or 2.12 wte/cot. Each special care patient needed 6.50 nursing hours each day, or 1.49 wte/cot. It is emphasised that each neonatal unit will have to take its own practices into account when calculating neonatal nursing requirements.

England↗
PubMed1993

Morphometric analysis of synovial membrane blood vessels in rheumatoid arthritis: associations with the immunohistologic features, synovial fluid cytokine levels and the clinical course.

The morphologic characteristics of the endothelial cells lining postcapillary venules are cytokine dependent and critical in facilitating the infiltration of mononuclear cells into synovial membrane in rheumatoid arthritis (RA). We determined the relationships between endothelial cell (EC) tallness, mononuclear cell infiltration and synovial fluid levels of interleukin 1 beta (IL-1 beta) and interleukin 6 (IL-6) at different stages of RA. EC tallness was greatest in synovial tissues obtained by needle biopsy of the knee joints from 18 patients with active RA who had never received disease modifying drugs (Group 1) (p = 0.000001 versus controls). EC tallness in tissues obtained from 18 patients with advanced disease undergoing knee arthroplasty (Group 2) was greater than controls (p = 0.001) only when vessels located in focal lymphoid aggregates were considered. Vascular proliferation was noted in both groups. Synovial fluid IL-6 levels were greatest in Group 1. IL-1 beta levels were greatest in Group 2. The total numbers of infiltrating mononuclear cells and the clinical measures of disease activity were similar in both groups. The differences in EC characteristics at different stages of RA suggest changing pathogenic mechanisms as disease progresses. Disease modifying antirheumatic drugs may contribute to the findings observed.

Anti-Inflammatory Agents↗
PubMed1992

Analysis of cell populations in rheumatoid arthritis synovial tissues.

Knee synovium, taken from patients with rheumatoid arthritis at the time of arthroplasty, was studied immunohistologically. Focal perivascular lymphoid infiltrates of different sizes were examined in detail to evaluate changes in cell populations as the infiltrate size increased. T cells formed the largest component of mononuclear cells of all aggregates. The large grade 3 aggregates contained substantial numbers of B cells arranged around a central venule and cells bearing the CD45RA+ phenotype. In contrast, the small grade 1 aggregates contained few B cells and the T-cell population contained relatively greater numbers of CD8+ cells. Cells bearing the CD45RO+ phenotype exceeded CD45RA+ cells in grade 1 aggregates. Detailed analysis of mononuclear cell aggregates of different sizes in the rheumatoid synovium suggests that the composition of each aggregate depends on the total number of mononuclear cells it contains.

Antigens, CD↗
PubMed1992

Prevalence of anti-Fab antibodies in patients with autoimmune and infectious diseases.

Sensitive ELISA were devised to examine the specificity of circulating IgM and IgA autoantibodies for whole human IgG, Fc and Fab fragments of human IgG. Sera from patients with autoimmune and infectious conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), tuberculosis (TB), infectious mononucleosis (IM) and cystic fibrosis (CF) were studied. Results of the ELISA assays using whole human IgG as antigen revealed that a proportion of patients in each of the groups studied had circulating IgM and IgA rheumatoid factors (RF). Fifteen normal individuals studied were negative. In the latex positive RA group, IgM RF and IgA RF had primarily anti-Fc reactivity (100% and 93% respectively), although 3/15 patients also showed IgM anti-Fab reactivity and one patient had high IgA anti-Fab activity. Patients with SLE and TB who had detectable RF levels also revealed predominantly anti-Fc specificity. In contrast, examination of 25 patients with IM showed positivity for IgM RF activity in 8% of patients using whole IgG as antigen, 24% positivity using purified Fc fragments as antigen and 45% positivity when plates were coated with Fab fragments. Similarly, a large number of CF patients (54%) also showed predominantly IgM anti-Fab activity. Of interest, 69% of the CF patients who were all studied at the time of bacterial infection had detectable IgA RF levels, with 46% of these patients showing both IgA anti-Fc and anti-Fab activity. These findings suggest that autoantibody specificities in autoimmune and infectious diseases are different.

Adolescent↗
PubMed1991

Effect of gold therapy on CD5+ B-cells and TCR gamma delta+ T-cells in patients with rheumatoid arthritis.

Circulating CD5+ B-cell levels in 15 patients with rheumatoid arthritis (RA) not receiving remittive therapy was significantly increased when compared to 17 normal controls (mean +/- SE: RA, 19.7 +/- 2.85%; controls, 11.6 +/- 1.67%; P less than 0.02). In contrast, 24 patients with RA receiving gold sodium thiomalate therapy (GST) had similar CD5+ B-cell levels (11.88 +/- 1.65) when compared to controls and significantly reduced levels when compared to the RA group not receiving remittive agents (P less than 0.01). Furthermore, TCR gamma delta+ T-cell levels were also assessed in these patients groups. These values were not significantly different between any of the groups (controls, 4.46 +/- 1.36%; GST, 6.88 +/- 1.73%; RA, 2.73 +/- 0.55%), although 42% of the GST treated group had gamma delta+ T-cell levels higher than the entire untreated RA group. No correlation was observed between the levels of TCR gamma delta + T-cells and CD5+ B-cells in any of these groups. These results suggested that therapy does influence the level of CD5+ B-cells and gamma delta+ T-cells in these patients.

Antigens, CD↗
PubMed1991

Induction of IgM and IgM-rheumatoid factor synthesis in vitro by indomethacin.

Indomethacin, which is thought to exert its therapeutic effect by inhibiting the synthesis of PGE2, is a commonly used first-line agent in the treatment of rheumatoid arthritis (RA). However, the effect of this drug on the humoral immune response in RA remains unclear. In this study, modulation of the in vitro synthesis of IgM and IgM-rheumatoid factor (RF) by indomethacin and prostaglandin E2 was examined in 11 patients with active RA and 10 normal controls. Indomethacin at a final concentration of 1 microgram/ml significantly enhanced IgM production (P less than 0.01) and RF production (P less than 0.02) in Staphylococcus aureus Cowan I (SAC) stimulated RA cultures when compared to controls in whom no net enhancement effect was observed. In the patients, this increase in IgM production was more pronounced than the corresponding increase in RF synthesis (P = 0.078), suggesting that IgM and IgM-RF-secreting RA plasma cells have different susceptibilities to PGE2 mediated suppression. Nonetheless, addition of PGE2 (10(-8) M final concentration) to the cultures inhibited IgM and RF production to a similar degree in the patient and control cultures. These findings demonstrate that PGE2 causes suppression of IgM and IgM auto-antibody production in vitro and that inhibition of endogenous PGE2 synthesis in RA patients treated with indomethacin results in a marked increase in the production of these antibodies.

Arthritis, Rheumatoid↗
PubMed1991

Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis.

Immunohistological features which might predict the clinical course and outcome of rheumatoid arthritis were sought by examining multiple synovial membrane samples obtained by needle biopsy from the knee joints of 57 patients who had not received disease modifying antirheumatic drugs. Clinical measurements, but not biopsies, were repeated one year and three years after starting treatment. A correlation between both the intensity of synovial lining layer thickening and mononuclear cell infiltration and the clinical status at the time of biopsy was seen. After three years of treatment the correlations were maintained in patients who had presented and persisted with milder disease but not in patients who had presented with more active disease.

Adolescent↗
PubMed1991

Tort reform and the obstetric access crisis. The case of the WAMI states.

The states of Washington, Alaska, Montana, and Idaho (WAMI) have all had declines in the proportion of physicians offering obstetric services during the past few years, a decline precipitated by rising medical malpractice premiums. One response to the problem of rising liability premiums has been the passage of extensive tort reform legislation. We present the results of recent studies of physicians' obstetric practices in the WAMI states and summarize the major changes in tort legislation and regulation that have occurred in these states. Most general and family physicians in the WAMI region no longer provide obstetric care; by contrast, more than 80% of the obstetrician-gynecologists in the WAMI states are still practicing obstetrics. Despite the fact that only a minority of family physicians are still active in obstetrics, most rural family physicians in all four states still deliver babies. Most physicians in all four states limit the amount of care they provide to those covered by Medicaid, which suggests that significant barriers to care exist for medically indigent persons. All four states have adopted significant tort reforms. Despite these changes in the legal environment, the cost of malpractice premiums and concerns over the likelihood of being sued continue to limit the number of physicians willing to provide obstetric care. Although it cannot be inferred from these data that tort reform has decreased the rate at which physicians give up obstetric practice, the evidence is compatible with such a conclusion.

Alaska↗
PubMed1990

Lymphocyte infiltration and the synthesis of IgM and IgA rheumatoid factors by rheumatoid synovial membrane.

IgM and IgA rheumatoid factor (RF) synthesis by synovial membrane mononuclear cells was measured in 14 patients with rheumatoid arthritis (RA). The results were compared with blood mononuclear cell cultures and correlated with the intensity of lymphocyte infiltration of the synovium. IgM RF was produced by all synovial cultures compared with 56% of blood cultures; IgA RF was produced by 86% of synovial cultures and by 21% of blood cultures. A correlation was observed between synovial IgM RF synthesis, but not IgA RF synthesis, and the intensity of T cell and B cell infiltration of the synovial membrane.

Adult↗
PubMed1990

Raised PPD antibodies in active pulmonary tuberculosis.

Antibodies to purified protein derivative of tuberculin (PPD) were measured in 47 patients with active pulmonary tuberculosis and in various control subjects using an enzyme linked immunosorbent assay. Raised IgG anti PPD antibodies were found in 30 patients with active tuberculosis, in one of 28 patients with miscellaneous non tuberculous diseases and in one of 49 healthy control subjects. This gave the assay a sensitivity of 65% and a specificity of 98%. Antibodies were also measured in a further 20 patients with suspected tuberculosis but in whom microbiological evidence was absent. In eight of these patients active tuberculous disease was subsequently validated on the basis of clinical response to chemotherapy: raised PPD antibodies were found in six of this group but in none of the remaining 12 patients in whom the diagnosis of tuberculosis was considered doubtful. Further studies showed that patients' PPD antibody level fell over a one year period of successful therapy and that tuberculin skin testing and BCG vaccination did not cause a rise in antibodies in healthy subjects. These results suggest that the measurement of PPD antibodies is a useful adjunctive test in the diagnosis of tuberculosis.

Antibodies, Bacterial↗
PubMed1990

Obstetric practice patterns in Washington state after tort reform: has the access problem been solved?

We surveyed all potential obstetric providers in Washington state in the spring of 1989 to determine whether the passage of tort reform in 1986 had improved access to care for rural and medically indigent women. We found that, although the exodus of family physicians from obstetric practice that had been observed between 1985-1986 appears to have slowed, there is still substantial net attrition among family physicians. As a result, rural patients are having increasing difficulty obtaining local access to obstetric care. By contrast, the supply of obstetricians and midwives seems to be stable. All three groups of providers are increasingly reluctant to provide care to the growing number of Medicaid patients. Although tort reform may have slowed the rate at which providers are quitting obstetrics, equilibrium has not yet been achieved. Shortages of rural physicians and inadequate Medicaid reimbursement rates must be addressed to improve obstetric access for underserved groups.

Health Services Accessibility↗