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Biomedical subjects

A Whelan

Publications and source records attributed to A Whelan.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Changes in lymphocyte infiltration of the synovial membrane and the clinical course of rheumatoid arthritis.

Multiple samples of synovial membrane were obtained by needle biopsy from 24 patients with rheumatoid arthritis (RA) before, and 1 year after, standard antirheumatic drug therapy was given. Changes in the immunohistologic features of the synovial membrane (read blindly) were compared with the clinical course of RA in each patient. A composite clinical index of disease activity (IDA) and spontaneous in vitro synthesis of IgM rheumatoid factor (IgM-RF) by blood mononuclear cells were also measured before and after treatment. In 16 patients (group A), the IDA indicated 26-69% improvement, and the values for spontaneous IgM-RF decreased substantially. In 8 patients (group B), the IDA indicated deterioration or no improvement, and the values for spontaneous IgM-RF were unchanged. In group A patients, the intensity of the T cell infiltrate decreased from a mean score of 1.3 to a mean score of 0.8 (P = 0.025). The ratio of T helper cells to T suppressor/cytotoxic cells was greater than or equal to 2:1 in 90% of group A patients before treatment, compared with 20% of these patients after treatment (P = 0.016), and the number of biopsy samples that contained identifiable B cells decreased from 36% before treatment to 7% after treatment. In group B patients, there were no changes in the intensity of T cell infiltration, the ratio of T helper cells to T suppressor/cytotoxic cells, or the number of biopsy samples with identifiable B cells.

Antibodies, Monoclonal↗
PubMed1989

Lymphoid irradiation in intractable rheumatoid arthritis. Long-term followup of patients treated with 750 rads or 2,000 rads.

Twenty patients with intractable rheumatoid arthritis were randomized to receive 750 or 2,000 rads of lymphoid irradiation (LI) in a double-blind comparative study, and were followed for a maximum of 48 months (mean 40 months) after treatment. During followup, sustained immunomodulation (including lymphopenia, particularly of the T helper cell subset; reduced ratio of helper cells to suppressor cells; and impaired in vitro lymphocyte proliferation in response to phytohemagglutinin and pokeweed mitogen) was observed. Significant improvements in early morning stiffness, Ritchie articular index, pain score, grip strength, and 15-meter walk time were observed in both treatment groups, but these were not sustained through the followup period. Progressive joint damage was observed radiologically in both groups during followup. Thus, LI induced sustained immunosuppression, but resulted in only short-lived clinical improvement and was associated with progressive joint erosion in these patients.

Arthritis, Rheumatoid↗
PubMed1989

Expression and regulation of the HLA-DR antigen on circulating monocytes isolated from patients with rheumatoid arthritis.

Using a modified radioimmunoassay, surface labeling of HLA-DR antigens on monocytes revealed reduced densities in patients with active rheumatoid arthritis (RA) (P less than 0.001) and in gold-treated patients (P less than 0.01) versus normal controls. Significant enhancement of DR antigen expression (P = 0.01), with values similar to those of normal monocytes, occurred in patient monocytes preincubated at 37 degrees C overnight, but not in monocytes preincubated at 4 degrees C. This suggested that a temperature-dependent metabolic process is required to enhance antigen expression. The addition of cycloheximide totally inhibited the enhancement of DR antigen density. Incubation of monocytes with exogenous prostaglandin E2 (10(-5)M final concentration) caused a reduction of DR densities on control and on RA monocytes, although this decrease was more marked in the controls. Addition of indomethacin did not affect DR antigen levels on control monocytes, but greatly enhanced the expression of DR antigens on RA monocytes. When HLA-DR antigen levels were estimated in detergent-solubilized membrane preparations, monocytes from patients with active RA demonstrated normal-to-increased densities compared with control monocytes. Thus, although RA monocytes possess a normal ability to synthesize DR molecules, surface expression of these molecules is inhibited; this inhibition may be mediated by prostaglandin E2 acting as a negative suppressive signal.

Arthritis, Rheumatoid↗
PubMed1989

Immunohistological features in the synovium obtained from clinically uninvolved knee joints of patients with rheumatoid arthritis.

The spectrum of immunohistological change in the affected joints of patients with rheumatoid arthritis has been well described. In this study, the immunohistological features in synovial membrane obtained from apparently uninvolved knee joints of 16 patients with active untreated rheumatoid arthritis were examined and compared to tissue from control subjects. Synovial tissue was obtained by needle biopsy. Hyperplasia of the synovial lining layer, present in 69%, was the most frequently observed abnormality in synovium obtained from uninvolved joints. Perivascular mononuclear cell infiltration was present in 31% and consisted predominantly of helper T-cells. Increased vascularity and fibrin deposition were not notable features. Clinically overt synovitis emerged in only two patients during a follow-up period of up to 36 months. In conclusion, a considerable degree of histological change was observed in the apparently uninvolved knee joints of patients with active rheumatoid arthritis. The presence of subclinical synovitis challenges current concepts of disease activity and clinical remission. Further study is required to determine whether the features described may be associated with progressive joint erosion.

Arthritis, Rheumatoid↗
PubMed1989

The immunohistologic features of synovitis, disease activity and in vitro IgM rheumatoid factor synthesis by blood mononuclear cells in rheumatoid arthritis.

The immunohistologic characteristics of synovial membrane obtained from patients with active rheumatoid arthritis (RA) were correlated with disease activity and spontaneous in vitro synthesis of IgM rheumatoid factor (RF) by peripheral blood mononuclear cells (MNC). Positive correlations were found between the intensity of inflammatory cell infiltration and both disease activity (p = 0.0007) and RF synthesis (p = 0.028). Moreover, the intensity of both T cell and B cell infiltration correlated significantly with disease activity. Within the group studied 3 previously described immunohistologic categories were identified. These categories could not be distinguished by clinical measurements, but did differ with respect to their capacity for spontaneous in vitro IgM RF synthesis by blood MNC. Our study provides evidence that a relationship does exist between the immunohistologic characteristics and disease severity in RA. Furthermore, the concept of distinct histologic categories of RA representing different immunopathogenic mechanisms is supported.

Adult↗
PubMed1988

Analysis of the histologic variation of synovitis in rheumatoid arthritis.

One hundred forty-five synovial biopsy specimens were obtained from 30 procedures performed on the knee joints of 29 patients with rheumatoid arthritis. All patients had clinically active rheumatoid arthritis and none had received slow-acting disease-modifying drugs or intraarticular corticosteroids. Scores were assigned to each biopsy specimen for each of 6 histologic features to quantify variation within each joint. In the majority of knee joint biopsies, there was considerable clustering of scores for all histologic features. Thus, on a scale of 0-10, 82% of the scores for synoviocyte hyperplasia were within 1 point of the median score for a given joint. Similarly, between 69% and 85% of the scores for the remaining features (fibrosis, vessel proliferation, perivascular infiltrates, focal aggregates, and diffuse infiltrates of lymphocytes) were within 1 point of the median values. Multiple biopsies were obtained at arthroscopy in 8 patients. Tissue was selected from areas of apparent maximal and minimal involvement, to enhance the likelihood of regional histologic variation. Of the scores for synoviocyte hyperplasia, 91% were within 1 point of the median values for a given joint, and of the scores for the remaining 5 features, 72-94% fell within 1 point of the median values. In addition, highly significant statistical correlations of the intensity of synovial lining layer hyperplasia, vessel proliferation, mononuclear cell infiltration, fibrosis, and clinical measurements of synovitis were observed.

Arthritis, Rheumatoid↗
PubMed1988

Myeloid antigen expression on common acute lymphatic leukaemia blasts after culture.

Blast cells from seven out of ten patients with common acute lymphoblastic leukaemia (cALL) developed the myeloid antigen MY7 (CD13) after culture, and one of these coexpressed the myeloid antigen MY9 (CD33). CD13 expression appeared to be independent of maturation since it could be induced more readily in cultures which did not contain the differentiation promoter 12-O-tetradecanoyl-phorbol 13 acetate (TPA). CD13 expression in culture was not seen on one null ALL, or 6 B-CLL investigated or on normal tonsillar B cells or PBMC under similar conditions. CD13 expression on cALL blasts probably represents evidence of abnormal gene expression in the leukaemic cells. However the absence of CD13 expression on the earlier B null ALL or the later B-CLL suggests we cannot exclude the possibility that CD13 expression is a feature of normal precursor B cells.

Adult↗