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Biomedical subjects

A J Malcolm

Publications and source records attributed to A J Malcolm.

At least 109 records · Page 6Linked to original sources

Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer.

In 135 primary breast cancers, there was a significant inverse relation between epidermal-growth-factor receptor (EGFR) and oestrogen receptor (ER) status, and a significant association with tumour size and poor differentiation. The relapse-free survival and overall survival were significantly worse for patients with EGFR+ tumours compared with EGFR- tumours. Relapse-free survival and overall survival were also worse for patients with ER- tumours compared with ER+ tumours. Of the 71 ER- patients 28 were EGFR+ and 43 were EGFR-. The relapse-free and overall survival for ER- but EGFR+ patients were significantly worse than for "double-negative" patients. Moreover, relapse-free survival and overall survival for "double-negative" patients were similar to those for ER+ patients. Thus EGFR status divides the ER- population into good and poor prognosis subgroups. The presence of EGFR was the most important variable in the primary tumours for predicting relapse-free and overall survival. Multivariate analysis showed that EGFR status was the most important variable in predicting relapse-free and overall survival in lymph-node-negative patients, and the second most important variable in lymph-node positive patients.

Adult↗

Lymphadenopathy in rheumatic patients.

Lymph node biopsy specimens from 22 patients with chronic inflammatory joint disease have been studied. The histology has been reviewed and immunoperoxidase staining carried out for the major immunoglobulin heavy and light chains, macrophage markers, and MT1, MB1 surface markers. Although two of these patients had been initially diagnosed and treated for malignant lymphoma, the clinical course has not substantiated the diagnosis, and on review malignancy could not be identified in any of the biopsy specimens. Careful attention to specific histological features, together with adequate clinical information, is therefore essential if the true nature of the lymph node enlargement is to be recognised. Clinical review of the 22 patients suggested that lymphadenopathy may, in some cases, be an early feature of inflammatory polyarthritis, and this was supported by the observation that 20% of patients with otherwise unexplained reactive lymphadenopathy developed an inflammatory polyarthropathy within one year of biopsy.

Adult↗

Cytogenic investigations in the assessment of response to treatment in neuroblastoma.

In a patient with stage IV disseminated neuroblastoma treated by chemotherapy extensive cytogenetic investigations were performed on the residual primary tumour and bone marrow immediately before myeloablative treatment and autologous marrow rescue. Two abnormal clones both showing lp+, a characteristic abnormality of neuroblastoma, were detected in cells from the residual primary tumour, providing direct evidence of persisting viable tumour. Such investigations should be a routine part of the assessment of response to treatment in patients with neuroblastoma, and could be extended to others in whom "second look" surgery is performed.

Adrenal Gland Neoplasms↗

The significance of hyperplastic lymphadenopathy.

The finding of reactive hyperplasia in a lymph node removed for diagnostic purposes often induces a feeling of disappointment in the clinician. However, this review indicates that reactive hyperplasia is frequently associated with a number of well-defined clinical conditions.

Arthritis, Rheumatoid↗

Simultaneous AL-type amyloid and light chain deposit disease in a liver biopsy: a case report.

A 57-year-old male caucasian presented with a peripheral neuropathy which had an autonomic component. Clinical examination revealed hepatomegaly and laboratory tests showed derangement of liver function tests and IgG lambda myeloma. Biopsy of the liver was performed. Histological examination revealed AL-type amyloid in the hepatic arteries and a perisinusoidal deposit of diastase resistant, periodic acid-Schiff positive material which did not react in the same way as the arterial deposit, giving no apple green birefringence when stained with Congo red. Immunohistochemistry showed the material to consist of lambda light chains. Electron microscopy confirmed that the material did not have the ultrastructural characteristics of amyloid. A diagnosis of light chain deposit disease concurrent with vascular AL-type amyloid was made.

Amyloid↗

Demonstration of a leukemia-associated antigen (CAMAL) in peripheral blood leucocytes of bone marrow transplant patients prior to relapse.

We have previously described a monoclonal antibody (CAMAL-1) that reacts in an indirect immunoperoxidase slide test at high frequency with cells of patients with acute nonlymphoblastic leukemia (ANLL), both at presentation and in remission (1). This article reports on a 12-month blind study carried out on peripheral blood leukocytes (PBL) of patients who had received bone marrow transplants for acute leukemias. PBL of patients attending the Royal Marsden Hospital were sent as cytospins to the University of British Columbia for staining and screening. Results of this study showed the following: of the 15 patients who remained in remission during the period of the study, 13 showed no abnormal increase in reactivity with CAMAL-1 (2 patients did show increased levels of reactivity over time); of the four patients relapsing but surviving within this period with ANLL, all showed elevated numbers of cells reactive with CAMAL-1 as long as 3 months prior to relapse (the two relapsing patients who had acute undifferentiated leukemia and acute lymphoblastic leukemia did not show elevations of CAMAL-1-reactive cells); of the 14 patients dying during this time of causes other than leukemia, none had elevated levels of CAMAL-1-reactive cells--and, of 4 patients dying in relapse, all had extremely elevated levels of CAMAL-1-reactive cells as long as 4 months prior to relapse. The implications of these observations are discussed.

Acute Disease↗

Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer.

Epidermal growth factor receptors are present in some breast cancers in man, and there is an inverse relation to oestrogen receptor state. We assessed the presence of epidermal growth factor receptors as a single prognostic indicator in a series of breast tumours by comparing this with the Bloom and Richardson scores for these tumours. One hundred and eight ductal tumours were examined for epidermal growth factor receptors by radioligand binding. There was a significant (p less than 0.01) correlation between the presence of the growth factor receptor and poor prognosis as assessed by the Bloom and Richardson score, suggesting that epidermal growth factor receptor state could be a useful prognostic marker. Epidermal growth factor receptor state was not significantly correlated with the lymph node state but showed a tendency to be associated with large tumours.

Breast Neoplasms↗

Characterization of lymphoid cells in the thyroid of patients with Graves' disease.

The distribution and function of lymphoid cells has been investigated in thyroid glands obtained at operation from 16 patients with Graves' disease (GD) using a peroxidase technique to enumerate total T and B lymphocytes as well as helper and suppressor T cell subsets in tissue sections. A spectrum of lymphocytic infiltration was observed and the increase from minimal numbers of immune cells in some GD thyroids to focal thyroiditis in others appeared to be due to a rise in all the lymphoid cell types analysed and was not the result of major change in any one lymphoid compartment. T cells were diffusely distributed whereas B cells tended to occur in aggregates. Small numbers of OKT6+ cells (possibly antigen presenting cells) were observed although these were less numerous than in lymphoid organs such as tonsil. Lymphoid cell suspensions prepared from the thyroid tissue of five of seven GD individuals treated pre-operatively with propranolol synthesized thyroid autoantibodies spontaneously in culture and this synthesis was decreased in the presence of pokeweed mitogen. Since the OKT8+ T cell subset has been shown to suppress immunoglobulin production by lymphocyte cultures containing mitogen, it appears that the suppressor T cells, which are readily demonstrable in GD thyroid sections, are functional. It seems unlikely, therefore, that a defect in this type of suppression is responsible for the initiation or perpetuation of the autoimmune response to thyroid antigens in GD.

Adult↗

Detection of a common leukemia-associated antigen in human myelogenous leukemia using immunoperoxidase.

The reactivity of a monoclonal antibody (CAMAL-1), raised to a purified leukemia-associated antigen (CAMAL) commonly expressed in or on cells from human myelogenous leukemics has been investigated using an indirect immunoperoxidase staining technique on single cell slide preparations of peripheral blood leucocytes (PBL) or bone marrow (BM) cells. A comparison of reactivity between CAMAL-1 monoclonal antibody (MAb) and rabbit anti-CAMAL serum using this procedure has clarified that differences in reactivities relate to antigen distribution and recognition. The specificity of the CAMAL-1 MAb has been established; most samples from patients with myelogenous leukemia (acute phase or remission and CGL chronic phase) show significantly increased numbers (greater than or equal to 1%) of CAMAL-expressing cells compared to those from normals or individuals with lymphoid leukemias. Evidence is presented that indicates that expression of the CAMAL antigen may represent continued underlying pathology in the acute myelogenous leukemia remission state.

Animals↗

A monoclonal antibody to myelogenous leukemia: isolation and characterization.

A purified antigen from human acute myelogenous leukemia (AML) cells has been used to produce a myelogenous leukemia-associated monoclonal antibody. In limited FACS-IV analyses the monoclonal antibody to leukemia (CAMAL-1) as well as a conventional rabbit antiserum have been used to positively identify AML or chronic granulocytic leukemia patient cell samples. Neither CAMAL-1 nor the rabbit antiserum bound appreciably to acute lymphocytic leukemia cells, normal bone marrow, or normal peripheral blood leukocytes. CAMAL-1 was shown to be specific for AML cell extracts in the ELISA and was successfully used as an immunoadsorbent for the purification of the AML antigen from cell extracts. No significant levels of equivalent antigen were found when cell extracts from normal cells, lymphocytic leukemia cells, and lymphoma cells were similarly absorbed. These findings indicate that CAMAL-1 shows considerable specificity for an antigen associated with cells from patients with myelogenous leukemia.

Animals↗

Analysis of human myelogenous leukemia cells in the fluorescence-activated cell sorter using a tumor-specific antiserum.

The properties of a rabbit antiserum (anti-AML) raised to a purified protein from membranes of human acute myelogenous leukemia (AML) cells is described. Bone marrow and peripheral blood leukocytes (PBL) from either normal individuals or patients with either myeloproliferative or other disorders were analyzed in a fluorescence-activated cell sorter (FACS IV) after labeling with anti-AML, normal rabbit serum (NRS), or antiserum raised to normal human membrane antigens. Of 40 cell samples from patients with acute myelogenous leukemia, 39 reacted strongly with the anti-AML antiserum. Similarly, all of 19 specimens from patients with chronic granulocytic leukemia reacted with the anti-AML. When 42 bone marrow or PBL samples from patients with a variety of lymphoproliferative disorders were examined, 2 specimens reacted with the antiserum, both from individuals with diagnoses of acute lymphocytic leukemia (ALL). None of the 14 normal bone marrow or PBL donor specimens tested reacted with the antiserum. It was also found that essentially all samples from patients in clinical remission from AML had high numbers of cells reactive with the anti-AML. When cells from such individuals were labeled and sorted on the FACS IV, it was found that cells fluorescing strongly with the anti-AML contained cells of both myeloid and lymphoid origin. The implications of these results are discussed.

Antibodies, Neoplasm↗

Pathologic effects of vaccinia virus on rabbit bone and marrow. An experimental study.

Although viruses have recently been implicated in the pathogenesis of Paget's disease and Perthes' disease, little information is available regarding bone and marrow response to the presence of a noncarcinogenic virus. Vaccinia virus was introduced into the medullary cavity of the femoral shaft of 30 New Zealand White rabbits, and an appropriate control inoculation was performed. Virus was recovered from the inoculation site in 50% of the animals at intervals to one month after inoculation. Histologic abnormalities were observed in 69% of the test femora; similar abnormalities were not observed in the control femora. These abnormalities consisted of bone and marrow necrosis, lymphocyte and plasma cell infiltration, and new bone formation. Some of the newly formed bone was also necrotic. The latter observation suggests an alternative mechanism for the death of new bone, which, in Perthes' disease, has customarily been attributed to repeated ischemic insults.

Animals↗

Squamous cell carcinoma of bladder. A review of 114 patients.

A retrospective review of 114 cases of squamous cell carcinoma of bladder presenting in Glasgow between 1964 and 1978 is described with emphasis on treatment and survival. Ninety-seven patients (92.4%) were found to have invasive tumours (T2-T4) at diagnosis. Metastatic disease was confirmed in only 10 patients (8.8%). Only 23.8% of patients were alive one year after diagnosis, the overall 5-year survival rate being 1.9%. The 5-year survival rates for patients with T2 and T3 disease following radical radiotherapy were 16.7 and 4.8% respectively. No conclusions concerning the role of total cystectomy could be drawn from this series because of the small number of patients undergoing the operation, but a review of the literature suggests this may be the treatment of choice.

Adult↗