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Biomedical subjects

A Lakhani

Publications and source records attributed to A Lakhani.

14 recordsLinked to original sources

Deletion of the long arm of chromosome 5 in essential thrombocythemia.

A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis.

Biopsy

Treatment of relapsed and refractory acute leukaemia with high-dose cytosine arabinoside and etoposide.

A total of 65 patients under the age of 55 with acute leukaemia received high-dose cytosine arabinoside (Ara-C) in combination with high-dose etoposide without an anthracycline. Complete remission rates for patients with relapsed or refractory acute myelogenous leukaemia (AML) were 15/25 (60%) and 11/16 (69%), respectively. The complete remission rate for patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) was 10/18 (56%). The treatment-related mortality was 17%. Nine patients whose leukaemia relapsed after matched allogeneic, sibling bone-marrow transplantation (BMT) were also treated in this way; the treatment-related mortality in this group was high (7/9) and the duration of remission in the two patients who responded, too short to justify this intensive treatment in such patients. Similarly, patients who underwent BMT after achieving a complete remission with high-dose Ara-C and etoposide did very poorly, only one patient surviving well and disease-free at 8 months. The important finding in this study was the high complete remission rate rapidly obtained in patients with relapsed or refractory AML without using an anthracycline.

Adult

Legionnaires' disease and the sick-building syndrome.

In October 1985, six cases of legionnaires' disease were associated with a police headquarters building. Four were amongst staff who worked in or visited the communications wing of the headquarters and two cases occurred in the local community. A case-control study implicated the operations room of the communications wing as the main area associated with infection. This wing was air-conditioned and smoke tracer studies showed that drift from the exhaust as well as from the base of the cooling tower entered the main air-intake which serviced the air-conditioning system. Legionella pneumophila serogroup 1 subgroup pontiac was isolated from water and sludge in the cooling tower pond. Contaminated drift from the top of the cooling tower was probably responsible for the two community cases. An additional discovery was that symptoms suggestive of the sick-building syndrome were associated with working in this wing.

Adult

Avoidable deaths.

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Adolescent

A simple method for culturing myeloma cells from human bone marrow aspirates and peripheral blood in vitro.

A double layer agar technique has been developed to grow myeloma colonies (MY-CFUc) from human bone marrow aspirates and peripheral blood. Heavily irradiated HL60 cells (5 x 10(5)/plate) are added to an agar underlay in growth medium containing 0.5% agar. Mononuclear cells from the test bone marrow or blood are overlayered in either 0.2 ml HL60-conditioned medium (HL60-CM) or in 0.5 ml growth medium containing 0.23% agar, and the cultures are incubated at 37 degrees C in an atmosphere of 5% CO2, 10% O2 and 85% N2. Colonies (greater than 50 cells) form between 2 and 3 weeks. Using this method 60/68 samples of bone marrow and 7/12 samples of blood from 54 patients have produced colonies in soft agar and in liquid on an agar underlay. The cells which form these colonies are of two distinct sizes, the larger cells being plasmacytoid and the smaller lymphoid. The two cell types are usually, but not always, present in separate colonies. Both plasmacytoid and lymphoid cells carry the isotype of the respective patient's myeloma protein and the plasma cell marker (HAN PC1). This technique has enabled us to culture myeloma cells from patients with as few as 2% plasma cells in the bone marrow but it does not permit the growth of normal B, T or granulocyte-macrophage colonies (GM-CFUc). The drug sensitivity of myeloma cells (MY-CFUc) compared with normal haemopoietic cells (GM-CFUc) can be measured using dose-response curves in individual patients. Furthermore, this method can detect resistant subpopulations within a given myeloma sample.

Bone Marrow

Melphalan and total body irradiation (TBI) versus cyclophosphamide and TBI as conditioning for allogeneic matched sibling bone marrow transplants for acute myeloblastic leukaemia in first remission.

Between June 1981 and April 1986 63 patients with acute myeloid leukaemia (AML) in first remission and HLA-identical sibling donors were entered into a prospective study comparing cyclophosphamide (CY) + total body irradiation (TBI) with melphalan + TBI as conditioning therapy prior to transplantation. Thirty-six patients received CY/TBI and 27 received melphalan/TBI. The actuarial probability of remaining in remission for patients receiving melphalan/TBI was 94% compared with 66% following CY/TBI (p greater than 0.01). By including a comparable group of 41 patients with AML in first remission, conditioned with CY/TBI prior to the onset of the study, the greater anti-leukaemic effect of melphalan/TBI compared to CY/TBI was unchanged and statistically the chance of this being wrong is 1 in 10 (p less than 0.1). The overall survival in remission of both arms of the study was the same with 15/27 patients (55%) surviving in remission following melphalan/TBI compared with 19/36 patients (53%) following CY/TBI. The benefit obtained in reduced relapse was offset by the combined nephrotoxic effect of melphalan and cyclosporin which was not identified until the programme had been underway for a period of time. This shows that misinterpretation of 'no survival advantage' for the new treatment may occur due to unforeseen and preventable toxicities.

Actuarial Analysis

Is the Jarman underprivileged area score valid?

A recently published validation of an underprivileged area score, which is intended to reflect factors that increase general practice workload or pressure on their services, was incomplete; a validation based on criteria other than the opinion of general practitioners is also required. Areas with higher mortality from diseases where general practitioner intervention can reduce mortality substantially are likely to have a greater need for general practice services. Similarly, the need for general practitioner services should be higher where the incidence of such treatable conditions is higher. This paper describes the association between Jarman's score and (a) mortality from causes that are amenable to general practice intervention and (b) incidence of two diseases where general practice intervention is important. Using these data the score appears to have external criterion validity and thus is likely to reflect, at least crudely, the need for general practitioner services.

Catchment Area, Health