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Biomedical subjects

R Champlin

Publications and source records attributed to R Champlin.

228 records · Page 13Linked to original sources

Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial.

We evaluated the efficacy of antithymocyte globulin for the treatment of moderate to severe aplastic anemia in a randomized controlled study. Eleven of 21 patients initially randomized to receive antithymocyte globulin (given intravenously on eight consecutive days) had sustained improvement in hematopoiesis within three months of treatment; none of 21 control patients who received supportive care alone improved (P = 0.0005). Six of 12 control patients who subsequently received antithymocyte globulin improved. Responders had gradual improvement in hematopoiesis, but none recovered completely normal peripheral-blood counts. The severity of bone-marrow failure, age, cause of aplastic anemia, and transfusion history had no apparent bearing on treatment outcome. The interval from diagnosis to antithymocyte globulin treatment correlated inversely with the chance of a treatment response, although this correlation was not statistically significant. These data indicate that antithymocyte globulin is effective in improving hematopoiesis in some patients with aplastic anemia.

Adolescent↗

Improved survival following bone marrow transplantation for aplastic anaemia.

We transplanted 46 patients with severe aplastic anaemia with a new pretransplant immunosuppressive regimen consisting of cyclophosphamide (200 mg/kg) and low-dose total body irradiation (3 Gy). This regimen (CY-TBI-2) was designed to decrease the high risk of graft rejection associated with the use of cyclophosphamide alone, without increasing the incidence of graft-versus-host disease (GHVD) or interstitial pneumonia (IPn). Two-year actuarial disease-free survival of patients conditioned with CY-TBI-2 was 62% (95% CI: 47-77%). Only one patient rejected her graft and the incidence and severity of GVHD and IPn were not increased compared to previous studies. Patients less than 25 years of age had excellent 2-year survival of 82% (95% CI: 69-95%). These data indicate that CY-TBI-2 is an effective means of preventing graft-rejection and achieving long-term disease-free survival in multiply transfused patients with severe aplastic anaemia.

Adolescent↗

Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia.

We performed a prospective randomized trial of antithoracic duct lymphocyte globulin (ATDLG), HLA-haploidentical marrow, and androgen (regimen ABA) versus androgen alone (concurrent STANDARD care controls) in 42 newly diagnosed individuals with severe aplastic anemia. ABA patients also were matched with patients from our preceding study (historical STANDARD care controls). Supportive care and pretreatment patient characteristics were the same in all groups. By life table analysis, 76% of patients receiving ABA are alive at 2 yr compared to 31% of the concurrent control group (p less than 0.002 versus ABA) and 19% of the historical controls (p less than 0.0001 versus ABA) given STANDARD care. ABA patients had greater hematologic improvement than either control group (p less than 0.001). However, improvement with ABA was often incomplete. Toxicity of ATDLG was considerable but manageable. Further studies to determine the mechanism of action and active component(s) of ABA are indicated.

Androgens↗

Humoral stimulation of hemopoietic progenitors from human fetal liver.

Hemopoietic cells from human fetal livers of 9-21 weeks gestation were cultured in semisolid media in vitro and in diffusion chambers implanted in mice. Myeloid colony formation in agar (CFU-C) was detected only in the presence of colony-stimulating factor. Formation of erythroid bursts in vitro was enhanced by addition of erythropoietin or erythroid-potentiating activity derived from a human T cell line (Mo). Fetal liver cells implanted in diffusion chambers gave rise to myeloid (CFU-DG) and occasionally to erythroid colonies. Administration of colony-stimulating factor derived from the T cell line to the host mice did not effect CFU-DG numbers. In contrast, a partially purified preparation containing erythroid-potentiating activity, caused a significant increase in the formation of CFU-DG. Similar stimulation was achieved by pretreatment of the diffusion chamber hosts with cyclophosphamide. None of these manipulations effected erythroid colony formation in diffusion chambers in mice.

Animals↗

Allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic or accelerated phase.

Eight patients with Ph1-positive chronic myelogenous leukemia (CML) in chronic or accelerated phase received high-dose cyclophosphamide, total body irradiation, and bone marrow transplantation from an HLA-identical sibling donor. All patients had prompt engraftment and achieved complete hematologic remission. Six patients remain alive and in continuous remission with a normal bone marrow karyotype 3-20+ mo posttransplant. One patient died from cytomegalovirus interstitial pneumonitis. Only one patient who was transplanted in accelerated phase relapsed 6.5 mo posttransplant and died in blast crisis. High-dose combined modality therapy is capable of producing sustained complete remissions in patients with CML treated during chronic or accelerated phase.

Adult↗

Prevention of graft rejection following bone marrow transplantation.

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

Actuarial Analysis↗

Bovine respiratory syncytial virus in Quebec: antibody prevalence and disease outbreak.

The prevalence of antibody to bovine respiratory syncytial virus in Quebec and the role of the virus in a respiratory disease outbreak was investigated. The indirect immunofluorescent, neutralization and haemagglutination inhibition techniques were used to carry out this study. Of the 1,444 adult animals examined 519 (35.9%) had antibody to bovine respiratory syncytial virus. These positive reactors were found in each agricultural region of Quebec. The highest (53.0%) and the lowest (21.8%) prevalence was observed in the sera collected by the laboratories of St. Hyacinthe and Sherbrooke. During a respiratory disease outbreak affecting 77 calves on a farm, bovine respiratory syncytial virus was shown to be associated with infectious bovine rhinotracheitis, bovine parainfluenza type 3, bovine viral diarrhea viruses and bovine adenovirus type 3 as detected by seroconversion. Of the 38 seroconverted animals 14 were seropositive to bovine respiratory syncytial virus.

Animals↗

An outbreak of severe pneumonia due to respiratory syncytial virus in isolated Arctic populations.

A rapidly developing outbreak of pneumonia in young infants was documented in two isolated Artic populations in May 1972. These were studied virologically, serologically and clinically. In addition to the two stricken communities, one apparently unaffected with serious clinical illness and a fourth, in which are located the major hospital and airport in the eastern Arctic, were also studied. One hundred and twenty-four patients were studied serologically and 81 respiratory and other specimens were obtained for virus isolation from 40 of these patients. Clinical records were kept of the outbreak in each area and a detailed questionnaire was filled out for 140 children and their families. Respiratory syncytial irus (RSV) was cultured from eight ill children. Electron microscopy provided the first evidence of RSV infection. A seroconversion rate of approximately 50% was seen in both affected communities as well as in the clinically unaffected one. The epidemic in the first two communities was characterized by severe pneumonia and frequent hospitalization but no cases of bronchiolitis were seen. No evidence for other causes of this outbreak could be obtained by testing for antibodies to influenza A and B, parainfluenza 1, 2 and 3, adenovirus and herpes simplex viruses. Unusual features of this epidemic of RSV infection include the high attack rate, severe morbidity, illness manifest almost exclusively as pneumonia rather than bronchiolitis and the difference between the expression of disease in different communities. Historical data and clinical observations were inadequate to explain these unusual features.

Adult↗

Studies on the composition of adjuvants which selectively enhance delayed-type hypersensitivity to lipid conjugated protein antigens.

Hen egg albumin (HEA), heavily conjugated with dodecanoic acid (D-HEA), stimulated sustained delayed type hypersensitivity (DTH) specific for HEA without detectable antibody formation in guinea pigs. An oil-in-water emulsion containing purified BCG cell walls attached to the oil drops was found to be a very effective adjuvant for enhancing DTH to D-HEA, but not to HEA. Animals immunized with D-HEA in the BCG cell wall emulsion produced skin test reactions 2.4 cm in diameter when challenged with HEA 21 days after a single immunization. Control animals immunized with D-HEA in saline produced skin reactions 1 cm in diameter to similar challenge. Neither group of animals produced detectable antibody to HEA-OR D-HEAmThe emulsion had no adjuvant effect if the BCG cell walls were suspended in the aqueous phase and not attached to the oil droplets. Dodecanoic acid conjugated Salmonella typhi organisms could be used in place of the BCG cell walls to produce effective adjuvant preparations. Fruend's complete adjuvant and other water-in-oil emulsions, however, were found to be ineffective adjuvants for enhancing the degree of DTH produced by D-HEA. Experiments with autoradiography demonstrated that effective adjuvant preparations promote the localization and retention of both 125-I-labeled D-HEA and 125-I-labeled BCG cell walls in the paracortical area of lymph nodes where they are in close proximity to many T-type lymphocytes which proliferate in the induction of DTH.

Adjuvants, Immunologic↗

Adenovirus type 19 keratoconjunctivitis in Canada.

We describe an outbreak of epidemic keratoconjunctivitis occurring in Montreal during the winter of 1974. Adenovirus type 19 was the only virus isolated. We confirm the presence of type 19 adenovirus in Canada; it produces severe keratoconjunctivitis. The incubation period, method of spread and clinical findings resemble those seen in outbreaks of type 8 EKC. The prevalence of adenovirus type 19 in the population of Canada is unknown. Although some object to the use of the term EKC for infection caused by adenoviruses other than type 8, we believe that EKC should be regarded as an entity requiring virus isolation and antibody determination to identify the adenovirus type responsible for it.

Adenoviridae↗