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Biomedical subjects

K Sullivan

Publications and source records attributed to K Sullivan.

At least 19 recordsLinked to original sources

Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone.

Sixty-eight patients with moderate (n = 15) or severe (n = 53) aplastic anemia were entered into a prospective, randomized, two-arm treatment study comparing antihuman thymocyte globulin (ATG), lower-dose methylprednisolone (LDM) and oxymetholone to ATG, higher-dose methylprednisolone (HDM), and oxymetholone. There were no differences between the two groups when comparing age, sex, etiology of aplasia, disease duration, severity of aplasia, or pretherapy granulocyte counts. Side effects of LDM and HDM were similar. Of the 64 patients evaluable for response to therapy, 12 of 33 (36%) who received LDM had complete, partial, or minimal responses compared with 15 of 31 patients (48%) who received HDM (P = .33). Actuarial survival at 4 years is 43% for patients in the LDM group and 47% for patients in the HDM group (P = .99). Causes of death included hemorrhage, infection, evolution to acute leukemia, and complications of subsequent bone marrow transplantation. Long-term complications included paroxysmal nocturnal hemoglobinuria (n = 3), evolution to myelodysplasia or acute leukemia (n = 6), and recurrent aplasia (n = 6). We were unable to show a significant difference in toxicity, response rate, or survival for patients treated with ATG, oxymetholone, and LDM compared with patients who received ATG, oxymetholone, and HDM.

Adult

Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors.

The safety and possible efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2-hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF-treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM-CSF-treated group had a higher proportion of "good risk" patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus-host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM-CSF is required to confirm these suggestive data.

Adult

A rapid polymerase chain reaction method for identifying fixed specimens.

DNA profiling analysis of preserved tissue samples was achieved by using an extraction method which incorporated the use of a chelating resin "Chelex" to chelate inhibitory polyvalent metal ions. An automated sequencer was used to estimate sizes of low molecular weight trimeric and tetrameric microsatellites labelled with fluorescent dyes. The entire analysis can be completed within 48h. Probabilities of chance association using two microsatellites were calculated as ranging between 10(-2) and 10(-4). The methods described have considerable potential for use in routine genetic analysis of preserved samples.

Alleles

Adult respiratory distress syndrome following cardiopulmonary bypass: incidence and prediction.

The outcome of adult respiratory distress syndrome complicating cardiopulmonary bypass has changed little in recent years. A retrospective, case-controlled study was designed to assess the incidence of the adult respiratory distress syndrome in these circumstances and the extent to which it could be linked with pre and peri-operative predictive factors. Eleven patients who developed the syndrome out of 840 who underwent cardiopulmonary bypass over a 9 month period were compared with 53 controls matched for sex, operation and surgeon. The incidence of adult respiratory distress syndrome and its mortality were 1.3% and 53% respectively. Significant predictors were a high intra and postoperative intervention score, the total volume of blood pumped during bypass (greater than 300 l) and age (greater than 60 years). These risk factors should alert the clinician to the possibility of severe postoperative pulmonary complications.

Adult

A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation.

Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.

Acute Disease

Diffuse anterior scleritis during OKT3 monoclonal antibody therapy for renal transplant rejection.

OKT3, a murine monoclonal antibody, is a potent, specific immunosuppressive agent used in solid-organ transplantation both as an adjunct during induction therapy and for treatment of steroid-resistant graft rejection. Minor, self-limiting ocular complications are often seen with this drug, of which conjunctivitis is the most common, occurring in approximately three-quarters of patients. We describe the more serious and previously unreported complication of diffuse anterior scleritis, which developed on the fifth day of OKT3 therapy in a 47-year-old man who had undergone cadaveric renal transplantation. Despite continuation of OKT3 treatment the scleritis resolved rapidly with increased dosages of prednisone.

Glucocorticoids

Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies.

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

Adult

Combined modality therapy for advanced, diffuse lymphocytic and histiocytic lymphomas.

Forty-six previously untreated patients with advanced aggressive non-Hodgkin's (34 poorly differentiated and mixed diffuse, 8 histiocytic and 4 undifferentiated) were treated with a 3 phase combined modality program employing cyclophosphamide (C), hydroxyl-daunomycin (H), vincristine (O), prednisone (P), procarbazine (P) [CHOP(P)] combination chemotherapy in an initial induction phase, radiotherapy and nonmarrow toxic chemotherapy as a second consolidation phase, followed by a third phase of CHOP(P) chemotherapy for four more cycles. Long-term maintenance therapy was not given. High dose involved field radiation in phase II was limited to volumes encompasing less than 50% of the marrow bearing skeleton. The large majority of patients (82%) had such widespread involvement that this limitation precluded the use of local radiation and were treated instead with a mean of 132 rad of fractionated total body irradiation (TBI). Thirty-eight patients (83%) achieved complete remission. Twenty-nine (66%) of the 44 patients evaluable for follow-up, and 22 (61%) of the 36 patients receiving TBI, remain alive in complete remission for observation periods of up to 26 months.

Adolescent