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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 109 records · Page 6Linked to original sources
PubMed1990

Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation.

Chronic graft-versus-host disease (GVHD) is an important complication of bone marrow transplantation. We analyzed risk factors for chronic GVHD in 2,534 recipients of HLA-identical sibling transplants surviving at least 90 days after transplantation. The actuarial probability of developing chronic GVHD within three years posttransplant was 46% +/- 3% (95% confidence interval). The most important risk factor for chronic GVHD was acute GVHD. The 3-year probabilities of chronic GVHD were 28% +/- 3%, 49% +/- 5%, 59% +/- 6%, 80% +/- 9%, and 85% +/- 15% for persons with grades 0, I, II, III, and IV acute GVHD, respectively (P less than .0001). Among patients with no or grade I acute GVHD, recipient age greater than 20 years, use of non-T-cell depleted bone marrow, and alloimmune female donors for male recipients predicted a higher risk of chronic GVHD. When all three adverse risk factors were present, the probability of chronic GVHD was 62% among persons with no prior acute GVHD and 85% among those with grade I acute GVHD. Among patients with grade II through IV acute GVHD, no other risk factor predicted chronic GVHD. These data identify individuals who might benefit from treatment strategies aimed at changing the incidence of chronic GVHD.

Acute Disease↗
PubMed1990

Serum erythropoietin changes in autologous and allogeneic bone marrow transplant patients.

Sequential changes in serum erythropoietin (sEPO) levels were measured by radioimmunoassay in six patients receiving autologous rescue (AR) and 11 patients receiving an allogeneic bone marrow transplant (BMT) for malignant disease. Longitudinal studies showed an inverse relationship between sEPO and haemoglobin levels in the autologous rescue and allogeneic transplant patients throughout the 130 d post-transplant study period. Early post-conditioning EPO responses were normal for the haemoglobin level in both groups, but after day 14 post-transplant, erythropoietin production in response to anaemia became impaired in one autologous rescue patient and eight of the 11 allogeneic transplant patients. There was no clear association between late impairment of sEPO production and conditioning therapy, infection, graft-versus-host disease, immunosuppressive therapy or serum creatinine. Blood transfusion requirements were similar for both groups in the first month after transplantation, but from days 31 to 90 post-transplant, BMT patients required an average of 5.5 units per patient compared with 1 unit per patient for the autologous group. Marrow transplant procedures do not affect early EPO responses but may diminish late responses. The potential value of exogenous rHuEPO in hastening engraftment and decreasing transfusion requirements, particularly for those patients who appear to have impaired EPO responses, remains to be shown by clinical trials.

Adolescent↗
PubMed1990

A novel human leucocyte surface membrane antigen defined by murine monoclonal antibody.

A murine monoclonal antibody has been produced which identifies a novel human leucocyte differentiation antigen. The antibody, designated WM-66, of IgM subclass, was cytolytic with human complement. WM-66 was shown to react with virtually all normal T and B lymphocytes from peripheral blood and lymphoid tissues, as well as blood monocytes and approximately 40% of bone marrow mononuclear cells. The antibody also bound to the majority of cases of chronic B-cell malignancies, including chronic lymphatic leukaemia and non-Hodgkin's lymphoma, but not to cases of acute leukaemia or to the majority of leukaemic and lymphoblastoid cell lines. WM-66 also reacted with epithelium of bronchus and salivary gland ducts. A single band of relative molecular mass 65,000 Daltons was immunoprecipitated from membrane extracts of normal lymphocytes and the B-cell line Daudi. Treatment of a number of WM-66-negative B-cell lines with neuraminidase resulted in WM-66 binding, indicating that the antigen exists in a covert form masked by sialic acid residues on a wider spectrum of cell types than was initially apparent. The reactivity pattern of WM-66 indicates that it recognises a previously undescribed surface membrane molecule with broad non-lineage-specific distribution on leucocytes. This has recently been confirmed at the Fourth International Workshop on Human Leucocyte Differentiation Antigens. Although the biological function of the molecule recognised by WM-66 is unknown, the lytic properties of the antibody suggest a possible in vivo therapeutic role as an immunosuppressant or for treatment of lymphoid malignancy.

Animals↗
PubMed1989

Extraovarian peritoneal serous papillary carcinoma. A clinicopathologic study of 31 cases.

The rate and clinical features of patients admitted to King George V Hospital with extraovarian peritoneal serous papillary carcinoma during a 9-year period were reviewed. In this time, 31 of 236 (13%) patients with an initial diagnosis of invasive serous ovarian carcinoma fulfilled the surgicopathologic criteria for this entity. All patients had disseminated tumor equivalent to ovarian Stage III and IV disease (International Federation of Gynecology and Obstetrics [FIGO]) and with predominantly high-grade neoplasms. They were managed by surgical exploration, tumor debulking where possible, and postoperative chemotherapy. A comparison with a contemporaneous series of 139 patients with primary epithelial ovarian carcinoma matched for stage and grade of disease and managed similarly showed no difference in actuarial survival. The median survival times were 11.3 months for patients with extraovarian serous papillary carcinomas and 13.5 months for patients with equivalent primary ovarian neoplasms. The features of the disease and the treatment regimens used are discussed.

Adult↗
PubMed1989

Expression of a novel human pan leucocyte differentiation antigen on leukaemic cells.

A murine monoclonal antibody has been produced which identifies a novel surface membrane antigen present on virtually all normal human leucocytes and leukaemic cells. The antibody, designated WM-65, reacted with over 95% of peripheral blood, tonsil and thymic lymphocytes, and with a similar proportion of monocytes and granulocytes. A majority of nucleated normal bone marrow cells were also reactive with WM-65; however, these included only a small proportion of myeloid progenitor cells. WM-65 reacted with a wide range of acute and chronic leukaemias of both myeloid and lymphoid types, and with corresponding cell lines, but did not react with non-haemopoietic cells. By immunoprecipitation and SDS-PAGE, WM-65 identifies a heavily glycosylated surface protein of molecular weight between 40 and 50 kD. This property, and the broad non-lineage-specific distribution of the antigen on haemopoietically-derived cells, indicates that WM-65 is different from other monoclonal antibodies with "leucocyte common" reactivity patterns. The extensive reactivity of WM-65 with leukaemic cells raises the possibility of therapeutic applications of the antibody in haematological malignancies.

Animals↗
PubMed1989

Cytokine activity after human bone marrow transplantation. III. Defect in IL2 production by peripheral blood mononuclear cells is not corrected by stimulation with Ca++ ionophore plus phorbol ester.

Previous studies have shown that interleukin 2 (IL2) production by peripheral blood mononuclear cells (PBMC) is severely impaired post allogeneic bone marrow transplantation, whereas production of interferon-gamma (IFN-gamma) is at most marginally depressed. To investigate the mechanisms behind this apparently differential inhibition of lymphokine production, we stimulated PBMC from recipients of HLA-identical sibling bone marrow transplants with phytohaemagglutinin (PHA), PHA + phorbol ester (PMA) (to bypass accessory cell requirements) or Ca++ ionophore + PMA (to bypass both accessory cell and T cell surface receptor (CD2 and/or CD3/Ti interactions). Increasing the potency of the stimulus increased the amount of IL2 and IFN produced by PBMC from both normal volunteers and from marrow transplant recipients, but for each stimulus the amount of IL2 produced by marrow transplant recipient PBMC remained 10-100-fold lower than that produced by normal PBMC, suggesting an underlying defect in IL2 production by marrow transplant recipient T cells, not due to accessory cell or CD2 defects. Selection experiments showed that CD3+ cells were the primary IL2 producers, and we were unable to demonstrate presence of suppressor cells in marrow transplant PBMC. Statistical analysis of the clinical factors possibly affecting lymphokine synthesis showed that in vivo cyclosporin A did not affect the in vitro capacity of PBMC to produce cytokines, although steroid therapy had a negative effect on IL2 production. The only variable significantly affecting IL2 and IFN production in marrow transplant recipients was increasing time post transplant. It is suggested that the defect in IL2 but not IFN production could be due to either a selective reduction in the frequency of IL2 producing cells as opposed to IFN producing cells, or to a reduction in the amount of IL2 produced per cell in marrow transplant recipients.

Adolescent↗
PubMed1989

A comparative study of proliferating (borderline) and invasive epithelial ovarian tumours in young women.

A series of 18 patients with proliferating or borderline ovarian tumours and 18 with invasive ovarian tumours is discussed. Proliferating tumours occurred at a younger mean age than invasive disease, and presented at an earlier stage, both contributing factors to their more favourable outlook. Histopathological assessment revealed that the majority of both proliferating and invasive tumours were of serous origin. Mucinous cell type occurred less often as did the endometrioid and clear cell types. The management of the proliferating tumours involved 'radical' surgical procedures in 11 of 18 (61.6%) patients. Only 7 patients (38.8%) had conservative surgical procedures performed. Six patients (33%) had adjuvant chemotherapy while 2 (11%) also underwent abdominopelvic irradiation. All patients with invasive disease had radical surgery and adjuvant chemotherapy and 2 also received abdominopelvic irradiation. The fact that epithelial malignancies of the ovary do occur in younger women needs to be remembered by gynaecologists contemplating surgical procedures on younger patients with adnexal masses. Proliferating or borderline tumours tend to occur more frequently in the younger age groups, and contrary to the implication of their name, they are associated with significant morbidity and mortality.

Adolescent↗
PubMed1989

Widespread pulmonary fibrosis as a major clinical manifestation of chronic graft-versus-host disease.

A 20-year-old Chinese male given an HLA-identical sibling bone marrow transplant for severe aplastic anemia, who had previously had chronic graft-versus-host disease (GVHD) of the mouth, developed myasthenia gravis and widespread pulmonary infiltrates with cough and exertional dyspnea at day 820 post-transplant. There was nothing to suggest aspiration pneumonia. Lung histology at day 940 showed some areas of dense pulmonary fibrosis, some areas of normal parenchyma, and some areas of widening of the interstitium and a mild lymphocytic infiltrate. Evidence of infection was not found. Treatment with cyclosporin and prednisone resulted in slow partial resolution of the infiltrates over 5 months. The myasthenia gravis was controlled with pyridostigmine. In view of the association with myasthenia gravis, of the absence of infectious agents and the response to immunosuppression, we conclude that widespread pulmonary fibrosis can be a major clinical manifestation of chronic GVHD. Examination of lung tissue to distinguish this from infective interstitial pneumonitis is essential.

Adult↗
PubMed1989

Recipients of HLA-identical sibling marrow transplants with severe aplastic anemia engraft more quickly, and those with chronic myeloid leukemia more slowly, than those with acute leukemia.

An analysis of the rate of leukocyte reconstitution in 164 recipients of HLA-identical sibling marrow transplants showed two factors to be independently influential. These were the underlying diagnosis and the type of prophylactic regimen used to minimize the risk of graft-versus-host disease. Patients with severe aplastic anemia had a faster rate of reconstitution of the total white blood cell count to levels of both 500 and 1000 x 10(6)/l than patients with acute non-lymphoblastic leukemia (ANL), acute lymphoblastic leukemia (ALL) or chronic myeloid leukemia (CML). Patients with severe aplastic anemia (SAA), however, did not show a faster rate of reconstitution of blood neutrophils. As well as being slower than patients with SAA for total leukocyte reconstitution, patients with CML were slower than patients with ANL and ALL in attaining a neutrophil count of 500 x 10(6)/l, and slower than patients with ANL in attaining a neutrophil count of 1000 x 10(6)/l. Patients given cyclosporin as the sole immunosuppressant prophylactic regimen post-transplant had faster reconstitution to total leukocyte counts of 500 and 1000 x 10(6)/l and to neutrophils of 1000 x 10(6)/l than patients given methotrexate alone, methotrexate and cyclosporin, or cyclosporin and T cell depletion of the donor marrow. No other factors (including the pretransplant preparative regimen) were significant in influencing the rate of leukocyte or neutrophil reconstitution. When only patients given cyclosporin were analysed, those with severe aplastic anemia continued to show a faster rate of leukocyte reconstitution to WBC 500 x 10(6)/l compared to patients with ANL, ALL or CML, and a faster rate to WBC 1000 x 10(6)/l than patients with CML.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Aplastic↗