Search PubMed⌕ Search

Biomedical subjects

P Halloran

Publications and source records attributed to P Halloran.

36 records · Page 2Linked to original sources
PubMed1989

Cyclosporine-induced deterioration in patients with AIDS.

Eight patients with AIDS (acquired immune deficiency syndrome) but free of life-threatening infection were treated with the immunosuppressive drug cyclosporine for a mean of 53.9 days. The serum cyclosporine levels were maintained in the desired therapeutic range. All eight patients experienced severe toxic symptoms, which necessitated discontinuation of cyclosporine therapy in six. The serum levels of creatinine, urea and potassium rose during treatment and fell after therapy was stopped. The total leukocyte count, hemoglobin level, platelet count, total T-cell count, and T4- and T8-cell counts all fell markedly during treatment. The total leukocyte count, platelet count, and T4- and T8-cell counts rose after therapy was stopped, but the hemoglobin level remained low. No patient experienced resolution of symptoms during therapy, and the condition of all patients improved after treatment was stopped. The results of this pilot study indicate that cyclosporine does not alleviate, and may worsen, the symptoms and laboratory findings in patients with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Factors influencing early renal function in cadaver kidney transplants. A case-control study.

We performed a multicenter study to investigate the problem of cadaver kidney transplants that never achieve function, or that recover after a period of delayed function, and we used multivariate techniques to model the results. Sixty-nine patients who received cadaver kidney transplants that never functioned (NF) were compared with 69 kidney recipients with early graft function (EF), and 69 with delayed but recovering graft function (DF), matched for transplant hospital and time. The results were analyzed using an unconditional logistic regression model. Risk factors for never-function transplants compared to immediate-function transplants were as follows: previous failed transplant, no polyclonal antilymphocyte globulin (ALG) prophylaxis, increasing anastomosis time, decreasing donor blood pressure, and prior transfusions in first but not subsequent transplant recipients. When technical failures were excluded, 88% of NF grafts displayed severe rejection, suggesting that rejection in a poorly functioning kidney is the principal cause of the NF outcome. Risk factors for delayed function compared to immediate function were these: increasing anastomosis time, no ALG, increasing total cold ischemia time, duration of end-stage renal disease (ESRD), and male sex. Thus ischemic and immunologic risk factors contributed to the DF and NF outcomes. This study suggests that efforts to reduce the delayed and never-function outcomes should be directed to the use of ALG prophylaxis and to the reduction of cold ischemia and anastomosis times, particularly in recipients who have lost a previous transplant.

Adolescent↗
PubMed1987

A randomized prospective trial of cold storage versus pulsatile perfusion for cadaver kidney preservation.

In a randomized trial conducted in 9 Ontario transplant centers, 107 cadaver kidney donors were randomized so that both kidneys were preserved either by simple cold storage (CS) or by pulsatile perfusion (PP). After exclusions and losses to follow-up, there were 90 patients in the CS group and 91 in the PP group. Total preservation times were similar in the two groups (27.7 +/- 12 and 30.5 +/- 10 hr), as was the proportion of kidneys with long (greater than 36 hr) storage times (21% and 26%). Twelve-month graft survival was 70% for CS and 75% for PP (not significant, NS); patient survival was 89% for CS and 95% for PP (NS). The incidence of kidneys that never functioned was also similar in the two groups (14% vs. 15%, respectively). However, the risk of early, reversible graft dysfunction was significantly higher for CS (44%) than for PP (31%). The same effect was observed with two independent methods of assessment of graft function. The chief effect of PP on renal function was in reduction of the mean serum creatinine at 1 week (632 mumol/L for CS vs. 403 mumol/L for PP, P less than .001). There was no significant influence of storage mode on the rapidity of urine output or number of dialyses required. No apparent effect of cyclosporine on the results with either preservation method was seen. We conclude that the case for retention of PP for kidney preservation now rests on its ability to achieve slightly better initial function than CS. However, the mild dysfunction observed with CS did not appear to translate into long-term detriment. When these considerations are weighed against the increased cost of PP, the advantage may lie with cold storage.

ABO Blood-Group System↗
PubMed1981

Autoantibody against fibroblasts in renal transplant recipients: analysis by 51Cr-release assays.

In testing for donor-specific alloantibody in renal transplantation we discovered that sera of many recipients lysed their own fibroblasts in complement-dependent cytotoxicity. The incidence of this autoreactivity before and during the first month post-transplant was 15 and 10% respectively, but rose to 48% after 2 months. There was a significant association between autoantibody formation and the presence of donor-specific alloantibody, but no association between autoantibody and graft survival. Autoantibody reactive with fibroblasts was three times more frequent than lymphocytotoxic autoantibody, and showed no association with the presence of such antibody, indicating that these autoantibodies were directed against different antigens. Reduction with 2-mercaptoethanol indicated that much of the autoreactivity was IgM. By absorption tests the autoantigen was shown to be expressed extensively on fibroblasts, but not on lymphocytes, platelets or red cells. Susceptibility to lysis by the autoantibody varied from day to day in the fibroblasts of a particular individual, and also varied from individual to individual. These results are of interest because they indicate that autoantibody formation in human renal allografts may result from chronic allogeneic stimulation, and that the antibody may be detecting a previously unknown fibroblast antigen.

Antibody Specificity↗
PubMed1976

Fc receptors and Ia antigens.

Antibody against Ia antigens inhibits the ability of B lymphocytes to bind aggregated immunoglobulin and to form EA rosettes. The explanation suggested for this phenomenon has been that Ia antigens are identical to or closely associated with Fc receptors. But a variety of observations preclude acceptance of this explanation since inhibition is also demonstrable with antibody against a wide variety of B cell surface components, including H-2K, H-2D, beta2 microglobulin, immunoglobulin, Ly 4.2. Furthermore, Fc receptor function can be separated from Ia antigens by capping or by isolation of membrane components. It seems likely that the mechanism of inhibition of Fc receptors by antibody against Ia antigens is part of a broader spectrum of effects induced when antibody binds to cell membrane antigens.

Animals↗
PubMed1975

Interactions of Fc receptors with antibodies against Ia antigens and other cell surface components.

Two Fc receptor-dependent tests were investigated to study the question of a relationship between Fc receptors and known cell surface antigens, in particular I region-associated (Ia) antigens: (a) a rosette assay with antibody-coated erythrocytes (EA) as indicator cells and normal mouse lymphoid cells as source of rosette-forming cells, and (b) a cytotoxicity test with antibody-coated erythrocytes as target cells and normal mouse spleen cells as a source of cytotoxic cells (K cells). EA rosettes were specifically inhibited by antibodies reacting with Ia antigens. Various other antisera reacting with antigens on B lymphocytes, like anti-Ly 4.2 (raised in H-2 identical mice), rabbit antimouse B-cell serum, or rabbit antimouse immunoglobulin, also specifically inhibited the rosettes. No inhibition occurred in the presence of allogeneic or xenogeneic antisera reacting with T lymphocytes. K-cell cytotoxicity was specifically inhibited by each of the antisera (reacting with either B cells or T cells). F(ab')2 fragments of anti-Ia antibodies could still specifically inhibit EA rosettes but they could not inhibit K-cell cytotoxicity. Similar results were obtained with F(ab')2 fragments of anti-immunoglobulin antibodies. These results indicate that the mechanism of inhibition of Fc receptors in the two tests was different. In neither of the tests could we find any evidence for a unique association between the Fc receptors and Ia antigens. The Fc receptors on K cells did not seem to be associated at all with Ia antigens.

Animals↗
PubMed1974

A new sensitive assay for antibody against cell surface antigens based on inhibition of cell-dependent antibody-mediated cytotoxicity. I. Specificity and sensitivity.

Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells ((61)Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays. A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2-11 times more sensitive for anti-H-2 antisera and 20-780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man.

Animals↗
PubMedDate not supplied

Cadaveric renal transplant failure: the short-term sequelae.

Quality of life was evaluated in 103 patients initially when each was placed on the waiting list for a cadaveric transplant. Patients who were not transplanted were reassessed six months after being placed on the waiting list. Patients who received a transplant were reassessed six months after the surgery. Cadaveric transplantation was performed in sixty-three patients by the time of follow-up. The mortality rate of 12.7 percent in transplanted patients after six months was more than twice that in patients who remained on the waiting list without a transplant, but this difference was not statistically significant. There was a graft failure rate of 23.6 percent among transplanted patients who survived six months. Graft failures were associated with some deterioration in subsequent physical activity (F = 5.4, p less than 0.03) but not in psychosocial functioning. Successful cadaveric transplants were associated with a marked and significant improvement in psychosocial well-being (F = 10.5, p less than 0.002) after six months even though physical activity did not increase. These findings suggest that 1) a successful cadaveric transplant is associated with an improved quality of life, 2) the graft failure rate of 23 percent with cadaveric transplantation is still appreciable but 3) graft failure is not necessarily associated in the short term with deterioration in psychosocial well-being.

Adolescent↗