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Biomedical subjects

J Bradley

Publications and source records attributed to J Bradley.

At least 19 recordsLinked to original sources
PubMed1992

The high-risk liver allograft recipient. Should allocation policy consider outcome?

The Boston Center for Liver Transplantation has accumulated one of the larger series of liver allograft recipients. This review has provided an opportunity to examine recent pronouncements by Medicare regarding patient selection and survival and to question whether the current allocation scheme best utilizes a scarce supply of donor liver allografts. Patients with primary biliary cirrhosis, sclerosing cholangitis, and metabolic derangements have enjoyed excellent survival: in aggregate, 78.9% at 1 year. In contrast, patients suffering from acute hepatic failure, patients requiring life support, or patients with primary graft failure who need a second liver transplant did poorly compared with other recipient groups: 45% 1-year survival. This center's experience reflects a more realistic expectation of patient survival because it considers the high-risk recipient by diagnosis and urgency status. This study also suggests that assessment of outcome should be a component of allocation planning in the future.

Adult↗
PubMed1992

Lipid parameters and apolipoprotein B RFLP studies: comparison of normal and coronary heart disease groups as defined by angiography.

We have compared the lipid and apolipoprotein values and the frequency of DNA polymorphisms of the apolipoprotein B gene detected with the restriction enzymes, Xba I and Eco RI in 122 patients with coronary heart disease (CHD) and 80 control subjects. The patients with coronary heart disease (CHD) were defined by > 70% stenosis in at least one major coronary artery whereas the controls showed no signs of coronary artery narrowing at angiography. When males and females were considered separately, differences in triglyceride, total cholesterol and high density lipoprotein-cholesterol (HDL-cholesterol) between CHD and control subjects were significant only for females. The polymorphism studies showed no significant differences between the control and CHD subjects except for a difference in the frequency in the females of the Xba I polymorphism (p < 0.05). The X1 allele (absence of the restriction enzyme cutting site) occurred significantly more often in the patient group than in the controls. Individuals with the X1X2 genotype had the highest serum total cholesterol whereas those with the X1X1 genotype had the lowest HDL-cholesterol value. Generally, the associations between the Xba I and Eco RI alleles and serum lipid levels were weak and inconsistent. Furthermore, even after careful selection of disease and control groups, a useful role for restriction fragment length polymorphism studies in assessing CHD risk in individual patients was not demonstrated.

Aged↗
PubMed1992

Mononuclear cells in normal colon and colonic carcinoma express the same T cell activation markers.

The proportion of mononuclear cells (MC) expressing some of the T cell activation markers in normal colon and colonic carcinomas was determined by immunoperoxidase staining and computer-assisted video image analysis (VIA). Tissue sections were stained with monoclonal antibodies against the T cell activation markers which included the MHC class II antigens DR, DP and DQ, interleukin 2 receptor (CD25) and the p180 (CD45RO) form of the leucocyte common antigen. The mean values for the proportion of leucocytes expressing these activation markers were 92% for DR, 61% for DP, 68% for DQ and 60% for CD45RO in tumours and 90, 62, 70 and 55% in normal tissue respectively. Few cells were stained for the IL2 receptor (mean values 7% for tumours and 5% for normal tissue) or the p220 form (CD45RA) of the leucocyte common antigen (mean values 6% for tumours and 4% for normal tissue). The proportion of MC bearing any of these markers in the normal colon was not significantly different from the matched colonic carcinomas.

Antibodies, Monoclonal↗
PubMed1992

Prevalence of latex sensitization among hospital physicians occupationally exposed to latex gloves.

Patients undergoing surgery who have a history of occupational exposure to latex gloves may be predisposed to intraoperative anaphylaxis caused by latex allergy. Thus, medical personnel who routinely wear latex gloves may be at higher risk than the general population. The prevalence of latex sensitization has not been reported previously among physicians using latex gloves in a North American hospital setting. Using a latex skin prick test (SPT), we determined the prevalence of latex sensitization among 101 staff anesthesiologists, radiologists, and surgeons who regularly use latex gloves and among 100 atopic controls who were not occupationally exposed to latex gloves. Latex SPT was positive in 10 of 101 physicians (rho = 0.099; 95% confidence interval [CI] 0.041, 0.157) and 3 of 100 controls. Subgroup analysis showed that 9 of 38 atopic physicians were SPT-positive (rho = 0.237; 95% CI 0.102, 0.372). Atopic physicians were more likely to be latex SPT-positive than either nonatopic physicians or atopic controls (atopic vs. nonatopic physicians: P = 0.0006, odds ratio = 19.2, 95% CI 15.4, 23.1; atopic physicians vs. atopic controls: P = 0.0005, odds ratio = 9.1, 95% CI 7.5, 11.6). We conclude that compared to nonatopic physicians exposed to latex, or nonexposed atopic controls, atopic physicians who wear latex gloves are at increased risk of latex allergy.

Adult↗
PubMed1992

Relationship between serum total cholesterol, infarct size, and early clinical outcome following acute myocardial infarction.

Strategies designed to decrease coronary heart disease (CHD) associated morbidity and mortality have focused primarily on established risk factors, including hypercholesterolemia, systemic hypertension, and cigarette smoking. Indeed, primary and secondary intervention trials have provided evidence for cholesterol lowering as an efficient method of CHD risk reduction. To test the hypothesis that serum total cholesterol influences the clinical outcome following acute myocardial infarction, infarct size, left ventricular ejection fraction, infarct-related vessel patency, and in-hospital cardiac events were determined in 106 consecutive patients given thrombolytic therapy within 5 h of symptom onset. Cumulative 48-hour creatine kinase (CK) release, peak CK, and calculated infarct size did not differ significantly between patients with an admitting serum total cholesterol level less than 200 mg/dl (group 1) and those with a cholesterol level greater than 250 mg/dl (group 2). Total cholesterol did not correlate with either cumulative CK release, peak CK, infarct size, vessel patency, or left ventricular ejection fraction. The vessel patency correlated inversely with cumulative CK release (r = -0.27; p = 0.03) and directly with left ventricular ejection fraction (r = 0.24; p = 0.03). The incidence of in-hospital cardiac events including recurrent infarction, congestive heart failure, and death was 6.9, 13.9, and 2.6%, respectively, and did not differ significantly between patient groups. Thus, although serum total cholesterol has been shown to influence CHD incidence, morbidity, and overall mortality, the findings of our study suggest that it does not impact directly on infarct size, left ventricular function, or in-hospital clinical outcome among patients sustaining acute myocardial infarction.

Cholesterol↗
PubMed1992

Age-related changes in the expression of T cell activation antigens following phytohaemagglutinin stimulation.

The role of accessory cells (AC) in the temporal expression of several key T-cell-activation-associated antigens has been studied in healthy aged subjects. Compared to responses seen in young adults, phytohaemagglutinin (PHA) induced weak proliferation in peripheral blood mononuclear cells from the aged and lower numbers of T cells expressing CD71, CD25, CD38 or HLA-DR. T cell responses to the monoclonal antibody OKT3, however, were normal. Whereas HLA-DR+ T cell numbers could be increased by raising the AC content (up to 50%) in cultures comprising purified T cells and graded numbers of autologous AC, CD25+ T cell numbers remained largely unaltered. Co-stimulation with PHA + phorbol myristate acetate in the absence of AC restored both proliferation and CD25 expression in the aged. These results indicate that T cells from the healthy aged show selective deficiencies in their capacity to respond to mitogenic stimuli and suggest that impaired PHA responsiveness is due, at least in part, to defective AC-derived signals.

Aged↗
PubMed1991

Cytoreductive surgery in disseminated non-seminomatous germ cell tumours of testis.

Between 1977 and 1988, 67 patients underwent surgical removal of residual metastatic deposits following an aggressive chemotherapy regimen (cisplatin, vincristine, methotrexate and bleomycin alternating with etoposide, actinomycin D and cyclophosphamide) for disseminated germ cell tumours of the testis (stage IIB or above). Ninety-one surgical procedures were performed. There were 63 (69 per cent) retroperitoneal lymph node dissections, 16 (18 per cent) thoracotomies, three (3 per cent) hepatic resections, three (3 per cent) craniotomies, five (5 per cent) delayed orchidectomies and one anterolateral decompression of the vertebral column. Nine (13 per cent) patients required a repeat retroperitoneal node dissection and one patient needed a repeat thoracotomy to remove recurrent metastatic deposits during the period of follow-up. Multivisceral resections and vascular reconstruction procedures were required in 20 (30 per cent) patients undergoing retroperitoneal node dissection. Fifty-five (82 per cent) patients remain in complete remission with a mean follow-up period of 49.6 months (range 2-121 months). Nine (13 per cent) patients died with metastatic disease between 2 months to 4 years after operation. There were three deaths in the perioperative period (4 per cent). The histology of the resected metastases revealed undifferentiated active tumour in 20 (30 per cent) patients, differentiated mature teratoma in 29 (43 per cent) patients and fibrosis/necrosis in 18 (27 per cent) patients. Twelve (60 per cent) patients with undifferentiated elements and 15 patients (60 per cent) with raised preoperative tumour markers (poor prognostic categories) are in complete remission. Cytoreductive surgery in patients with metastatic germ cell tumours offers the best chance of remission following chemotherapy even in poor prognostic group categories.

Adolescent↗
PubMed1991

Age-related changes in the activation requirements of human CD4+ T-cell subsets.

In agreement with previous studies, we found that the proliferative response of unfractionated T-cells to phytohaemagglutinin (PHA) was severely impaired in healthy aged individuals (70-85 years). On the other hand, we did not observe significant differences between aged and young adults in T-cell responsiveness to mab OKT3 (anti-CD3). PHA responses in "old" T-cells could be substantially improved, however, by the addition of recombinant interleukin-2 (rIL-2) or KOLT2 (anti-CD28 mab). When individual CD4+ T-cell subpopulations were isolated from young and old donors and stimulated with PHA in the presence of autologous accessory cells, age-related deficiencies were seen in both CD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) cell populations. Further analysis using a panel of coactivators in cultures depleted of accessory cells identified specific abnormalities in the CD2 or alternate pathway of T-cell activation. These were predominantly seen in CD4+ naive T-cells. The capacity of rIL-2, KOLT2, and PMA to restore, at least partially, T-cell responsiveness in the aged suggests a defect(s) in an early signal transduction mechanism.

Adult↗
PubMed1991

On-line determination of glucose in biotechnological processes: comparison between FIA and an in situ enzyme electrode.

Two different analysis techniques for on-line monitoring of glucose in biotechnological processes have been tested: an in situ enzyme electrode and a flow injection analysis system (FIA). The measuring ranges, detection limits, response times and the reliabilities of each system have been compared during monitoring of batch and continuous cultures of Saccharomyces cerevisiae.

Computers↗
PubMed1991

Triage model for suicidal runaways.

A triage model for suicidal youth was evaluated at four community-based agencies over a 30-month period. The program screened youths for suicidal ideation, trained staff in assessment, instituted agency protocols for triage, and established a multilevel mental health service network. The number of suicide attempts decreased after implementation of the program, psychiatrists' evaluations of suicidal tendencies concurred with those of the staff, and additional community-based agencies voluntarily introduced the program.

Adolescent↗
PubMed1991

The H3 anti-phospholipid idiotype is found in patients with systemic lupus erythematosus (SLE) but not in patients with syphilis.

The human H3 idiotype, defined by a mouse monoclonal antibody S2.9, is commonly found in patients with SLE where it is correlated with the amount of anti-cardiolipin antibodies. No correlation between the amount of anti-cardiolipin antibody and the H3 idiotype is found in patients with syphilis. Using the S2.9 antibody, serum from each of 10 patients with SLE and eight patients with syphilis was separated into H3-bearing and H3-negative fractions. Comparison of the partition of anti-cardiolipin antibody in these two groups of patients revealed that much of the anti-cardiolipin antibody (44-91%) was found in the H3+ fraction in patients with SLE; in patients with syphilis, virtually none of the anti-cardiolipin antibody was H3+. In patients with SLE, the H3+ fraction contained both IgG and IgM and antibodies of both kappa and lambda light chains. The H3+ fraction was polyspecific and frequently reacted with dsDNA.

Antibody Specificity↗
PubMed1991

A randomised double-blind trial of cyclosporin and azathioprine in refractory rheumatoid arthritis.

Fifty-two patients with severe rheumatoid arthritis (RA) from four Australian centres were randomised to receive cyclosporin A (CSA) (n = 25) or azathioprine (AZA) (n = 27) for six months. Initial mean doses of CSA and AZA were 4.2 mg/kg and 1.7 mg/kg respectively. The mean doses of CSA and AZA at six months were 3.4 mg/kg and 1.9 mg/kg. Assessments of side-effects and outcomes of benefit were made monthly by independent, blinded observers. Both treatment groups exhibited statistically significant improvement in standard outcome parameters when compared with baseline values. However, there were no statistically significant differences in these parameters between the two groups. There was a mean increase in serum creatinine concentration associated with CSA; no persons were withdrawn from the study for this reason. Seven CSA recipients (three gastrointestinal symptoms, two neurological symptoms, two other) and 12 AZA recipients (six gastrointestinal symptoms, four inefficacy, two other) withdrew from treatment prematurely. Seven CSA recipients became hypertensive and four required anti-hypertensive therapy. Adverse events not requiring cessation of therapy were more commonly seen among CSA patients. In this group of severely affected patients with RA both cyclosporin and azathioprine were effective therapies. CSA toxicities were predictable and manageable but required close monitoring.

Adult↗
PubMed1991

Catalysis of poliovirus VP0 maturation cleavage is not mediated by serine 10 of VP2.

The maturation of the poliovirus capsid occurs as the result of a single unexplained proteolytic event during which 58 to 59 copies of the 60 VP0 capsid protein precursors are cleaved. An autocatalytic mechanism for cleavage of VP0 to VP4 and VP2 was proposed by Arnold et al. (E. Arnold, M. Luo, G. Vriend, M. G. Rossman, A. C. Palmenberg, G. D. Parks, M. J. Nicklin, and E. Wimmer, Proc. Natl. Acad. Sci. USA 84:21-25, 1987) in which serine 10 of VP2 is activated by virion RNA to catalyze VP4-VP2 processing. The hypothesis rests on the observation that a hydrogen bond was observed between serine 10 of VP2 (S2010) and the carboxyl terminus of VP4 in three mature picornaviral atomic structures: rhinovirus 14, mengovirus, and poliovirus type 1 (Mahoney). We constructed mutant viruses with cysteine (S2010C) or alanine (S2010A) replacing serine 10 of VP2; these exhibited normal proteolytic processing of VP0. While our results do not exclude an autocatalytic mechanism for the maturation cleavage, they do eliminate the conserved S2010 residue as the catalytic amino acid.

Amino Acid Sequence↗
PubMed1991

Quality assurance of immunodiagnostic tests in Australasia.

A Royal College of Pathologists of Australasia (RCPA) sponsored Quality Assurance Program (QAP) in Clinical Immunology, involving 128 laboratories over a 1 yr period, revealed the following: successful participation in the program by 16 overseas laboratories (distant from Australia); only 30% of laboratories succeeded in returning their results by the scheduled date on every occasion; quantitation of urinary total protein and Bence Jones protein was poor and varied over a log scale; immunofixation was more successful in characterizing urinary paraprotein than immunoelectrophoresis; densitometry of protein electrophoresis appeared the method of choice in quantitating serum paraproteins accurately; nephelometric techniques gave better concordance between laboratories than turbidometric, radial immunodiffusion or agglutination techniques; poor concordance between laboratories in detecting weakly positive antinuclear antibodies (ANA); some laboratories had difficulties in identifying ANA patterns (only 60% of laboratories correctly identified the anticentromere pattern); few laboratories could correctly identify antibodies to extractable nuclear antigens (ENA); flow cytometry gave a smaller dispersion of lymphocyte subpopulation percentages than microscopy. A method was established to rank laboratory performance of selected tests over the 1 yr period. Such a comparative ranking scheme may alert laboratories in identifying specific or generalized deficiencies in performance.

Antibodies, Antinuclear↗
PubMed1990

The use of computer-assisted video image analysis in the enumeration of immuno-stained cells in tissue sections.

A novel method of computer-assisted video image analysis (VIA) was used to determine the number of immunostained cells in tissue sections. This method permitted an accurate and objective quantification of cells of a particular phenotype. This enumeration was achieved by measuring the area stained by a test monoclonal antibody (such as the T cell marker, CD3) and comparing it with the area stained by a leukocyte common (LCA) monoclonal antibody (CD45). The proportion of T cells within the total leukocyte population in a particular tissue was then calculated. The differentiation of positive (stained) and negative (unstained) cells was uniformly maintained by setting the computer to detect a threshold for staining intensity. This enabled consistency to be maintained within a tissue section as well as between sections stained with the same antibody. In the present study, we determined the phenotype of leukocytes in colonic carcinomas by VIA and compared this with results obtained by normal visual analysis. The VIA method showed distinct advantages over normal visual analysis especially in sections which contained moderate numbers of stained cells.

Antibodies, Monoclonal↗
PubMed1990

T cell activation in the elderly: evidence for specific deficiencies in T cell/accessory cell interactions.

We studied T cell activation in the healthy aged (greater than 70 years) by examining lymphocyte proliferative responses to various mitogenic stimuli in accessory cell (AC)-dependent and AC-independent systems. Results show that despite a near normal response to the anti-CD3 monoclonal antibody (mAb) OKT3, peripheral blood mononuclear cells (PBM) from the elderly exhibit a profound reduction in phytohaemagglutinin (PHA)-responsiveness (approximately 30% of young adults). This deficit becomes even more severe at suboptimal doses of PHA. Adding exogenous interleukin-2 (IL-2) or pretreating the AC population with gamma interferon (IFN-gamma) returns the level of proliferation to that seen with young adults. Furthermore, replacing "old" AC with AC from young adults or with U937 (a monocytic cell line) in T cell/AC cell-mixing experiments restores PHA-responsiveness in 70% of cases. On the other hand, AC from the aged fully support PHA responses in T cells from young adults. In AC-depleted cultures, purified T cells from the aged respond normally to the co-mitogenic stimuli, PHA + PMA. Taken together, these results suggest that the age-associated diminution in PHA-responsiveness is due, at least in part, to specific deficiencies in T cell/AC communication.

Aged↗