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Biomedical subjects

J Bashford

Publications and source records attributed to J Bashford.

15 recordsLinked to original sources
PubMed1999

Safe mobilization of normal progenitors in advanced chronic myeloid leukemia with intensive chemotherapy and granulocyte-colony stimulating factor.

Twenty-one patients with advanced chronic myeloid leukemia (late chronic phase (n = 8), accelerated phase (n = 11) and blast crisis (n = 2)) were treated with idarubicin, cytarabine, and etoposide followed by G-CSF and subsequent collection of peripheral blood progenitor cells in the early recovery phase. Treatment was reasonably well tolerated with no deaths or intensive care admissions. Despite the advanced phase of disease and heavy pretreatment with cytotoxics and interferon-alfa, 11 of 21 patients (52%) achieved a cytogenetic response. Of the nine major cytogenetic responses (complete (n = 3) and partial (n = 6)), seven achieved adequate progenitor collections for consideration for autologous transplantation. The only predictor of response was disease duration (P = 0.02). With a median follow-up of 1171 days from treatment it appears unlikely that G-CSF contributed to disease progression. Survival post-IcE was predicted by disease stage (P = 0.0001). Intensive chemotherapy followed by G-CSF allowed adequate yields of predominantly Philadelphia chromosome negative progenitor cells to be obtained from one-third of patients with advanced CML.

Adult↗
PubMed1999

Should the corticosteroid to bronchodilator ratio be promoted as a quality prescribing marker?

In recent years the ratio of inhaled corticosteroid:bronchodilator (C:B) prescribing has been promoted as a quality marker for asthma treatment and cross-sectional data indicate an association with hospital admissions. If prescribing advice has been followed then it can be hypothesised that the C:B ratio will have increased and hospitalisation decreased. The West Midlands General Practice Research Database was used to monitor changes in the C:B ratio and hospital referrals for asthma between 1993 and 1996. The C:B ratio increased from 0.5 to 0.6 (P<0.001) and hospital referrals decreased from 7% to 4% per annum (P<0.001). Overall, 38% of the variation in hospital referrals was explained by the C:B ratio. This is higher than previous studies, perhaps because the study was longitudinal and the ratio assessed accurately in terms of volume rather than prescription items. When measured in defined daily doses, the C:B ratio does appear to have validity as an indicator of good prescribing in primary care. The General Practice Research Database offers an opportunity for assessing the validity of prescribing indicators before they are considered for wider use by Primary Care Groups and Health Authorities.

Administration, Inhalation↗
PubMed1999

Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia.

BACKGROUND: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. AIMS: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. METHODS: Seventeen patients with ET and a platelet count > 600 x 10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). RESULTS: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728 x 10(9)/L (95% CI 611-845 x 10(9)/L) to 412 x 10(9)/L (95% CI 319-504 x 10(9)/L) (p < 0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to < 600 x 10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. CONCLUSIONS: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.

Adolescent↗
PubMed1999

Multicycle high-dose chemotherapy and filgrastim-mobilized peripheral-blood progenitor cells in women with high-risk stage II or III breast cancer: five-year follow-up.

PURPOSE: To determine the safety and efficacy of multiple cycles of dose-intensive, nonablative chemotherapy in women with poor-prognosis breast cancer. PATIENTS AND METHODS: Women with stage II breast cancer and 10 or more involved nodes or four or more involved nodes and estrogen receptor-negative tumors and women with stage III disease received three cycles of epirubicin 200 mg/m2 and cyclophosphamide 4 g/m2, with progenitor cell and filgrastim support every 28 days (n = 79) or 21 days (n = 20). Patients were reviewed at least twice yearly thereafter. Twenty-six patients had bone marrow and apheresis collections assessed for the presence of micrometastatic tumor cells. RESULTS: Ninety-nine women (median age, 43 years; range, 24 to 60 years) were treated. Ninety-two completed all three cycles of chemotherapy. The major toxicity was severe, reversible myelosuppression that was more prolonged with successive cycles, and this did not differ between patients given treatment every 28 days and those treated every 21 days. Febrile neutropenia occurred in 176 (61%) of 287 cycles. Severe mucositis (grade 3 or 4) occurred in 23% of cycles but tended to be short-lived and was reversible. The cardiac ejection fraction fell by a median of 4% during treatment, and three patients developed evidence of cardiac failure after chemotherapy. Two patients (2%) died of acute toxicity. Three of 26 patients had evidence of circulating micrometastatic tumor cells. The actuarial distant disease-free and overall survival rates at 60-month follow-up were 64% (95% confidence interval [CI], 53% to 75%) and 67% (95% CI, 56% to 78%), respectively. CONCLUSION: Multiple cycles of dose-intensive, nonablative chemotherapy is a feasible and safe approach. Disease control and survival are similar to those in other studies of myeloablative chemotherapy in poor-prognosis breast cancer. The regimen is being evaluated in a randomized trial of the International Breast Cancer Study Group.

Adult↗
PubMed1996

High response rates with short infusional 2-chlorodeoxyadenosine in de novo and relapsed low-grade lymphoma. Australian and New Zealand Lymphoma Study Group.

Thirty-five patients (eight de novo, 27 relapsed disease) with low-grade non-Hodgkin's lymphoma (diffuse small lymphocytic, follicular small cleaved cell, follicular mixed cell, and lymphoplasmacytoid) were treated with 2-chlorodeoxyadenosine (2CdA) at a daily dose of 0.14 mg/kg for 5d (2 h infusion) for an average of three cycles. Minor treatment delays, generally due to haematological toxicities, occurred in nine of 105 cycles. Major toxicities were lymphopenia, neutropenia and thrombocytopenia. Opportunistic infections occurred in seven patients. Overall response rate was 69% (five complete, 19 partial) reaching 88% for de novo patients (two complete, five partial). Elevated beta 2-microglobulin level was negatively predictive of response (P = 0.0014). Eight of 24 responders relapsed, with a median follow-up of 13 months. 2CdA administered as an intermittent infusion shows considerable single-agent activity in low-grade lymphomas achieving high response rates of prolonged duration. Consideration of schedules where 2CdA is alternatively administered with combination chemotherapy appears warranted.

Adult↗
PubMed1991

Treatment of acute promyelocytic leukaemia relapsing after allogeneic bone marrow transplantation with all-trans-retinoic acid: suppression of the leukaemic clone.

We describe the clinical experience of a male patient with acute promyelocytic leukaemia, relapsing after sex-mismatched allogeneic bone marrow transplantation and treated with all-trans-retinoic acid. Resolution of the coagulopathy was observed by day 7 of therapy. A complete remission was achieved by day 47 after a period of pancytopenia, dysplastic myeloid maturation and bone marrow hypocellularity with necrosis and fibrosis. Serial cytogenetic analyses revealed a progressive loss of the male leukaemic clone [46XY,t(15;17)] and emergence of normal female (donor) cells [46XX] which became completely dominant with remission. Adverse effects of all-trans-retinoic acid included bone pain and a prominent leucocytosis requiring leukaphereses and hydroxyurea therapy. All-trans-retinoic acid can induce complete remission of recurrent acute promyelocytic leukaemia following bone marrow transplantation. The data suggest that remission is due to differentiation and suppression of the leukaemic clone while allowing repopulation of the marrow with non-malignant cells.

Adult↗
PubMed1988

A radiographic technique of interest to physical anthropologists.

A radiographic technique for processing a large number of human crania was developed to aid in the diagnosis of porotic hyperostosis in a large skeletal population. These images are made directly onto photographic paper, thereby reducing costs and increasing the rate of processing. The technique is especially well suited for radiographing human skeletal material and gives excellent diagnostic image quality.

Anthropology, Physical↗
PubMed1983

High-affinity erythrocyte rosette formation and inhibition in premalignant disease of the uterine cervix.

Total lymphocyte counts, total rosette formation, high-affinity rosette formation, and the rosette inhibition titer were studied in 104 patients with dysplasia, carcinoma in situ, or Stage I squamous cell carcinoma of the uterine cervix. Although no changes were detected in total lymphocytes or total rosette formation, a significant decrease (p less than 0.001) was observed in high-affinity rosette formation in patients with moderate and severe dysplasia and carcinoma in situ. The rosette inhibition titer was significantly increased (p less than 0.001) in all stages of dysplasia and carcinoma in situ; incubation of patients' serum with normal lymphocytes did not reproduce this change but significantly decreased the rosette inhibition titer of the patients' lymphocytes (p less than 0.001). No change in high-affinity rosette formation or the rosette inhibition titer was observed in patients with Stage I squamous cell carcinoma as compared to controls. These changes are postulated to represent alterations in the normal balance of T-cell differentiation during the early stages of tumor development.

Adult↗
PubMed1983

Depression of high-affinity rosette formation in dysplasia and carcinoma in situ of the uterine cervix: mediation by serum factors.

High-affinity erythrocyte rosettes (HA-RFC) have been shown previously to be depressed in patients with dysplasia and carcinoma in situ of the uterine cervix. The effect of serum from these patients on HA-RFC in normal lymphocytes was studied to further elucidate the nature of immunological changes in early cancer. Sera from patients with dysplasia and carcinoma in situ significantly decreased HA-RFC in normal lymphocytes as compared to control serum (p less than 0.001). Serum inhibitory activity correlated well (p less than 0.001) with HA-RFC in the patients' lymphocytes and was postulated to represent the presence of a serum factor in these patients. Liquid chromatography studies showed this factor to have a molecular weight of approximately 50,000. Additional factors with molecular weights of 73,000 and 88,000 were present in patients with carcinoma in situ but not in patients with dysplasia. Serum inhibitory activity was not observed in Stage I squamous cell carcinoma. These factors may represent antigen-specific suppressor factors produced in response to the expression of neoantigens by premalignant cells and may be involved in "sneaking through" of developing tumors.

Blood↗