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Biomedical subjects

D Linch

Publications and source records attributed to D Linch.

31 records · Page 2Linked to original sources

Autologous bone marrow transplantation for acute leukaemia in remission.

Between 1980 and 1985, 175 patients with acute leukaemia in first or subsequent complete remission (CR) were treated by chemotherapy or chemoradiotherapy followed by transfusion of autologous bone marrow cells that had been collected days or months previously. In 85 cases, autologous marrow cells were treated ex vivo with cytotoxic drugs or monoclonal antibodies with the intention of removing residual leukaemic cells. The actuarial relapse-free rate was 52% at 2 years. Of 89 patients autografted for acute non-lymphocytic (myeloid) leukaemia (ANLL), 60 were treated in first remission and 18 in second CR; their relapse-free rates at 2 years were 67% and 41% respectively (P less than 0.001). In contrast, of 77 patients autografted for acute lymphoblastic leukaemia (ALL), 32 were treated in first CR and 28 in second CR and their actuarial relapse free rates at 2 years were 56% and 55% respectively (P = NS). There was no significant difference in leukaemia relapse rates between patients autografted with purged and those autografted with non-purged marrow cells. These preliminary results suggest that autologous bone marrow transplantation may be valuable if offered to patients with ANLL in first CR or to patients with ALL in first or second CR but the need for marrow purging remains uncertain.

Acute Disease↗

A monoclonal antibody reactive with normal and leukemic human myeloid progenitor cells.

Anti-MY9 is an IgG2b murine monoclonal antibody selected for reactivity with immature normal human myeloid cells. The MY9 antigen is expressed by blasts, promyelocytes and myelocytes in the bone marrow, and by monocytes in the peripheral blood. Erythrocytes, lymphocytes and platelets are MY9 negative. All myeloid colony-forming cells (CFU-GM), a fraction of erythroid burst-forming cells (BFU-E) and multipotent progenitors (CFU-GEMM) are MY9 positive. This antigen is further expressed by the leukemic cells of a majority of patients with AML and myeloid CML-BC. Leukemic stem cells (leukemic colony-forming cells, L-CFC) from most patients tested were also MY9 positive. In contrast, MY9 was not detected on lymphocytic leukemias. Anti-MY9 may be a valuable reagent for the purification of hematopoietic colony-forming cells and for the diagnosis of myeloid-lineage leukemias.

Antibodies, Monoclonal↗

Chronic T cell lymphocytosis: a review of 21 cases.

Twenty-one patients are described with a proliferation of morphologically mature T lymphocytes. The clinical course was chronic in most, and splenic enlargement the main clinical finding; skin involvement and lymphadenopathy were rare. The mean lymphocyte count at presentation was 8 X 10(9)/1 (range 0.75-24 X 10(9)/1). Nineteen of these patients showed some form of cytopenia (18 neutropenia, two red cell aplasia, eight thrombocytopenia) and one had hypogammaglobulinaemia. Seven patients had long-standing arthropathy serologically proven to be rheumatoid arthritis and these had previously been considered to have Felty's syndrome. Five of the group have died (three with an aggressive course), but most have remained stable for prolonged periods with a slow increase in peripheral lymphocyte count and marrow infiltration. Spontaneous regression was never observed but in two patients a prolonged remission was achieved by chemotherapy. The lymphocytes were morphologically and phenotypically homogeneous at presentation and remained so post-splenectomy; they contained azurophilic granules, stained with acid phosphatase but weakly or not at all with alpha napthyl acetate esterase. Membrane phenotyping shows the majority of the cells to be E+, Fc gamma+, OKT3+, OKT8+. Most cells do not stain with OKT1-like reagents and a significant number express HLA-Dr. From these and other reported cases it is clear that this condition represents a distinct entity resulting from the expansion of a subset of cytotoxic/suppressor T cells--the question of the benign or neoplastic nature of the disease remains open. Using T cell-specific antisera and E-rosetting techniques, a small percentage of CLL cases have been shown to be of T-cell origin (TCLL) (Dickler et al, 1973; Lille et al, 1973). Estimates of the percentage vary but in most series T-CLL has been diagnosed in less than 5% (Brouet & Seligmann, 1981), and this is supported by date from the M.R.C. Leukaemia Unit which found T-CLL in only 1.5% of 600 cases of CLL examined by marker studies (D. Catovsky, unpublished). Amongst the published reports of T-CLL a variety of clinical and morphological entities have been described including T prolymphocytic leukaemia (TPLL) (Brouet et al. 1975) and adult T cell disease in Japanese (Uchiyama et al, 1977) and West Indian Caribbean groups (ATLL) (Catovsky et al, 1982). In the original series of Brouet & Seligmann (1981) the group was defined as presenting in middle age with marked hepatosplenomegaly, some lymphadenopathy, skin involvement and with an aggressive disease course; peripheral blood and marrow lymphocytosis were variable.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

High-dose cyclophosphamide with autologous marrow transplantation for small cell carcinoma of the bronchus.

Twenty-five patients with previously untreated small cell carcinoma of the bronchus have been treated with cyclophosphamide 160-200 mg/kg and subsequent radiotherapy to the primary site. Eighty-four percent of patients responded to the single cycle of chemotherapy, with 56% attaining a complete response. Median duration of remission was 43 weeks and median survival 69 weeks. 2-Mercaptoethane sulphonate was given to prevent urothelial toxicity. Autologous bone marrow transplantation was used to mitigate bone marrow depression but sequential delay in reinfusing cryopreserved bone marrow did not alter the period of cytopenia. Other toxicities were mild. The procedure proved safe and manageable. High-dose chemotherapy may prove to be useful in the initial management of this tumour.

Adult↗

Immunocompromise syndrome in homosexual men. Prevalence of possible risk factors and screening for the prodrome using an accurate white cell count.

The immunocompromise syndrome in homosexual men in the USA is thought to be associated with cytomegalovirus (CMV) infection and nitrite intake. Such men often have a lymphopenia. In a clinic in London 76% of 46 unselected homosexual men and 50% of 76 heterosexual controls had serum CMV IgG antibody at a titre of 1/16 or more (p less than 0.01). No case of excretion of CMV in the urine was found. Thirty per cent of the homosexual men admitted to using nitrites. These figures suggest that this population of homosexual men uses nitrites less often than their counterparts in the USA and is less likely to have evidence of active or past CMV infection. In addition, these male homosexual patients seem to be less promiscuous than those reported from the USA. Mean accurate total and differential white blood cell counts, using the Haemalog D automatic white cell counter, were no different in homosexual men (and various at risk subgroups of them) than heterosexuals, suggesting that the prodrome to the immunocompromise syndrome was not present in the London clinic population.

Acquired Immunodeficiency Syndrome↗

High-dose cyclophosphamide with autologous marrow transplantation as initial treatment of small cell carcinoma of the bronchus.

Sixteen patients with untreated small cell carcinoma of the bronchus received cyclophosphamide in a total dose of 160-200 mg/kg. Autologous marrow transplantation was used to minimise the period of hypoplasia and 2-mercaptoethane sulphonate to prevent urothelial toxicity. The procedure was well tolerated, with predictable and manageable toxicity. Complete radiological and bronchoscopic response was achieved in seven patients and partial response in a further seven. High-dose cyclophosphamide may be a useful initial treatment for this disease.

Adult↗

Unusual phenotype and function of an expanded subpopulation of T cells in patients with haemopoietic disorders.

We have studied two patients, one with red cell aplasia and the other with neutropenia. Both showed lymphocytosis. In both cases, 90-100% of E rosetting cells were T cells as defined by the monoclonal antibodies UCHT1 and OKT3. The majority of these cells also carried the OKT8 suppressor/cytotoxic marker and were HLA-DR- and Fc gamma R-positive. In spite of the similarity of this phenotype to that reported for suppressor cells, these cells failed to suppress pokeweed mitogen-induced polyclonal Ig synthesis. Cells from both patients also failed to respond significantly to Con A and PHA. They were, however, unable to suppress the Con A responses of normal donors although cells from one patient were able to suppress completely a normal PHA response. These results demonstrate the existence of a genuine subset of T cells with Fc gamma receptors but suggest that not all such cells have typical suppressor function.

Agranulocytosis↗

Isolation of human haematopoietic progenitor cells using monoclonal antibodies.

Studies of the differentiation of human haematopoietic cells have been greatly advanced by the use of in vitro cloning techniques to enumerate the myeloid and erythroid progenitor cells which form colonies in semi-solid medium. The granulocytic/monocytic colony-forming cells (CFU-GM) and erythroid burst-forming cells (BFU-E) are thought to be mononuclear cells, similar in size to medium size lymphocytes, but their ontogenetic relationship to other progenitor cells and the putative pluripotential stem cell remains obscure. This is partly because elucidation of parent-progeny relationships requires the isolation of precursor cells before they acquire mature phenotypic characters. Physical methods have failed to separate CFU-GM cleanly from other cells because of their heterogeneity, and immunologically specific markers for human progenitor cells have not been reported. We report here that a fraction containing all the granulocytic/monocytic and erythroid progenitor cells, as well as cells which may be lymphoid progenitors, can be isolated from bone marrow using a combination of monoclonal antibodies.

Bone Marrow Cells↗

Tension pneumoperitoneum complicating cardiac resuscitation.

A case of gastric rupture and tension pneumonperitoneum following cardiac resuscitation is presented. Respiratory embarrassment necessitated emergency decompression by needle puncture of the peritoneal cavity, followed by laparotomy and repair of the gastric tear. The post-operative course has been satisfactory. The aetiology of the gastric rupture is discussed and recommendations are made for the prevention and treatment of this unusual complication of combined mouth to mouth respiration and external cardiac massage.

Humans↗