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Biomedical subjects

K Atkinson

Publications and source records attributed to K Atkinson.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry.

A questionnaire comprised of a series of clinical vignettes illustrating potential difficulties in diagnosis, grading and treatment of chronic graft-versus-host disease (GVHD) was completed by 65 bone marrow transplant physicians from 51 transplant centers worldwide. The concordance index (CI) for responses to each question was calculated using the formula CI = 2p-1, where p was the percentage agreement among respondents. Possible responses ranged from 0 (no agreement) to 1.00 (perfect agreement). Responses indicated moderate (CI = 0.55), high (CI = 0.88) and moderate (CI = 0.54) agreement among transplanters for diagnosis, grading and treatment of chronic GVHD, respectively. Disagreement was observed in (1) diagnosis of uncommon manifestations of chronic GVHD; (2) in interpretation of symptoms which occur less than 2 months after transplant; (3) in interpretation of persistent stable symptoms; and (4) in deciding whether to treat chronic GVHD limited to skin. The results point to potential problem areas in designing and interpreting clinical trials to prevent or treat chronic GVHD and highlight the need for improved diagnostic criteria.

Adolescent↗
PubMed1988

Cytokine activity after human bone marrow transplantation. II. Production of macrophage procoagulant activity and the cytokine regulating its production, macrophage procoagulant inducing factor.

The production of procoagulant activity by circulating monocytes and its regulation by a cytokine secreted by mitogen-stimulated peripheral blood mononuclear cells was investigated in recipients of HLA-identical sibling bone marrow transplants. Blood monocyte numbers reached the normal range within 3 weeks of transplant. After stimulation with lipopolysaccharide, macrophage procoagulant activity was found to be within the normal range in all patients at all times post transplant. It did not appear to correlate with the presence or absence of graft-versus-host disease. Surprisingly, and in marked contrast to our previously documented severe depression of interleukin 2 production by transplant recipients' peripheral blood mononuclear cells, the mitogen-induced production of the cytokine that induces procoagulant activity production (macrophage procoagulant inducing factor, MPIF) was also normal in the majority of patients when assayed using the responsive myelomonocytic cell line RC-2A. These findings suggest firstly that monocyte differentiation and function normalize rapidly post transplant; and secondly, when taken together with previous studies, that the ability of peripheral blood mononuclear cells to synthesize cytokines post transplant varies greatly according to the specific cytokine involved.

Adolescent↗
PubMed1988

High incidence of early leukemic relapse in patients given cyclosporin and T cell depleted HLA-identical sibling marrow transplants for acute leukemia in first remission.

Twelve patients with acute nonlymphoblastic leukemia (ANL, n = 6) or acute lymphoblastic leukemia (ALL, n = 6) in first complete remission received cyclophosphamide 120 mg/kg and total body irradiation (TBI) 12 Gy followed by HLA-identical sibling marrow that had been depleted of T cells by incubation with anti-CD2 (with or without anti-CD8) monoclonal antibody and rabbit complement. These 12 patients were compared historically to 25 patients with ANL (n = 15) or ALL (n = 10) in first remission given cyclophosphamide 120 mg/kg and TBI 12 Gy followed by non-T cell depleted HLA-identical sibling marrow for parameters of relapse and survival. Thirty-six of the 37 patients received cyclosporin as post transplant prophylaxis for graft-versus-host disease (GVHD). All surviving patients have been followed for a minimum of one year from transplant. The actuarial rate of leukemic relapse in the T-depleted group was 62% compared to 37% in the non-depleted group (p less than 0.02). Additionally, relapse occurred significantly earlier post transplant in the T-depleted recipients (p = 0.012). Actuarial survival at two years post transplant was 24% for the T-depleted recipients and 41% at six years post transplant for the non-depleted recipients (not significant, p = 0.37). We have previously shown that GVHD is less severe in patients given T cell depleted transplants. Taken together, these findings suggest that (under the protocol conditions used) a graft-versus-leukemia effect is not separable from a GVHD effect in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗