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Biomedical subjects

S Ariad

Publications and source records attributed to S Ariad.

51 records · Page 3Linked to original sources

Prognostic factors in chronic myeloid leukaemia--importance of staging or disease biology.

The presenting clinical, haematological and cytogenetic features of 215 patients with a haematological diagnosis of chronic myeloid leukaemia (CML) were analysed with a view to defining prognostic factors. Of the 215 patients, 166 (77%) were found to be Philadelphia chromosome (Ph')-positive. The frequency of Ph' and complex Ph' abnormalities was similar for black and white patients. Black patients, however, had a significantly higher frequency of additional clonal chromosome abnormalities at presentation compared with whites (15/87 v. 1/79). Blacks also tended to present with more advanced disease, lower haemoglobin values, higher white cell counts, larger spleens and a higher frequency of lymphadenopathy and leukostasis. Median duration of survival from diagnosis of Ph'-positive patients was 44 months for whites and 30 months for blacks. The poorer survival of the black patients was in part accounted for by the poor survival of patients with additional clonal chromosomal abnormalities over and above Ph'. Black patients with only simple Ph' or complex Ph' had a similar survival to whites. In a multivariate analysis, the significant factors determining survival were: (i) the presence of additional clonal chromosomal abnormalities; and (ii) peripheral blast count over 5%, platelet count outside the normal range and haemoglobin value less than 10 g/dl. These factors defined subgroups of patients with median survival ranging from 12 months to 62 months. The inclusion of patients with variable prognoses needs to be taken into account when evaluating the results of new treatment modalities for CML.

Female↗

Erythropoietin response in anaemic patients with multiple myeloma and other lymphoid malignancies infiltrating the bone marrow.

Immunoreactive erythropoietin levels were measured in 42 patients with lymphoid malignancies with anaemia and bone marrow involvement. Results were compared to a control group of 16 patients suffering from anaemia due to other causes. Significant inverse correlations between serum erythropoietin level and haemoglobin concentration were shown for the patients with lymphoid malignancies and also for the control subjects. Overall, the erythropoietin levels of patients with lymphoid malignancies with bone marrow infiltration and with normal renal function did not differ significantly from erythropoietin levels of the anaemic controls. We conclude that anaemia in patients with lymphoproliferative disorders with bone marrow infiltration and normal renal function is caused primarily by a diminished/inadequate response to erythropoietin at the level of the target cell.

Anemia↗

High-dose etoposide in treatment of metastatic breast cancer.

High-dose etoposide (1,500-2,500 mg/m2) was used for the treatment of 23 previously treated patients with advanced breast cancer. Six of 23 (26%) showed objective regression with a median duration of response of 5 months. Responses were seen at all sites apart from bone. Response was related to dose level with 11/23 responses of measurable lesions occurring at doses greater than or equal to 2,000 mg/m2 as compared to 2/23 responses at a dose of 1,500 mg/m2. The treatment regimen was able to be given on an outpatient basis with only routine supportive measures. High-dose etoposide may come to play a role in high-dose combination chemotherapy regimens for advanced breast cancer.

Breast Neoplasms↗

Interferon-alpha induced autoimmune hepatitis in a patient with Philadelphia chromosome-positive chronic myeloid leukemia with cytogenetically normal T lymphocytes.

We report the occurrence of autoimmune hepatitis after treatment with interferon-alpha in a patient with Philadelphia chromosome-positive chronic myeloid leukemia. Cytogenetic and molecular genetic studies of the T lymphocytes in this patient demonstrated that the T lymphocytes were not part of the leukemic clone. The role of interferon in the production of autoimmune abnormalities is reviewed.

Adult↗

High-dose chemotherapy: therapeutic potential in the age of growth factor support.

The steep dose-response curve for most chemotherapeutic drugs and the need to overcome tumor resistance has resulted in renewed interest in the use of high-dose chemotherapy. Bone marrow rescue has allowed the dose-limiting barrier of hematopoietic suspension to be overcome. However, despite such salvage methods and the use of blood products and effective antibiotics, myelosuppression remains a major obstacle to treatment. The use of recombinant colony-stimulating factors in combination with bone marrow following high-dose chemotherapy may well shorten the period of neutropenia and reduce the frequency of neutropenia-related complications, thus making high-dose treatment more acceptable.

Antineoplastic Agents↗

Platelet-derived growth factor (PDGF) in plasma of breast cancer patients: correlation with stage and rate of progression.

Plasma levels of platelet-derived growth factor (PDGF) were measured in 58 female patients with breast cancer and in 9 normal female control subjects by means of a specific radioimmunoassay. Levels in normal control subjects were all below the lower limits of detection by the assay (1.56 fmol/100 microliters plasma). Two of 17 (12%) patients with stage 2 breast cancer had detectable plasma levels. Among patients with Stage 4 breast cancer 13/41 (32%) had significantly elevated levels (greater than 2 times the lower limit of sensitivity of the assay). Patients with elevated PDGF levels had a significantly greater degree of metastatic involvement and significantly shorter survival. Apart from being a marker of aggressive high bulk breast cancer, PDGF may be involved in the acceleration of growth of some metastatic breast tumors.

Biomarkers, Tumor↗

Adverse cardiovascular responses to thyrotropin-releasing hormone (200 micrograms) in cardiac patients.

Although a pressor effect of 500 micrograms i.v. thyrotropin-releasing hormone (TRH) in noncardiac patients has been reported, the effect of a lesser dose of TRH (200 micrograms) in cardiac patients has not been evaluated. We performed a 200 micrograms i.v. TRH test to exclude thyrotoxicosis in 20 cardiac patients, aged 38 to 42 years. No clinical side effects were noted, but increments in systolic and diastolic blood pressure of 21.8 +/- 2.7 and 17.3 +/- 1.6 mm Hg (SE), respectively, were documented. Mean arterial pressure rose from 104.9 +/- 2.9 to 123.7 +/- 5.5 mm Hg (SE) after TRH (P less than 0.001). In nine patients the pressor response persisted for 5 to 20 min, and blood pressures of 220 mm Hg systolic and 145 mm Hg diastolic were recorded. We conclude that the 200 micrograms TRH i.v. has a significant pressor effect.

Adult↗

Effect of activators and inhibitors on human blood platelets: study by freeze-fracturing technique and electron microscopy.

Samples of normal human platelet-rich plasma were activated by ADP (0.5 microM and 20 microM) or by cold treatment (4 degrees C). The effects of incubation in EDTA, colchicine or cytochalazin B were also studied. Samples were prepared by the freeze-fracturing technique and examined by electron microscopy. Faces of fractured membranes were examined for aggregation of particles, for pore-openings in the membrane, and for the general morphological appearance of the membrane-fractured faces. No aggregation of particles was found in platelet-rich plasma preparations treated with ADP, EDTA, colchicine or cytochalazin B, nor did the pore openings reveal any changes following these treatments. We conclude that platelet activation and an increase in microviscosity of the platelet membrane is not due to platelet aggregates in the membrane.

Adenosine Diphosphate↗