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Biomedical subjects

H E Davidson

Publications and source records attributed to H E Davidson.

5 recordsLinked to original sources

Retroviral transduction of enriched hematopoietic stem cells allows lifelong Bcl-2 expression in multiple lineages but does not perturb hematopoiesis.

Transduction of hematopoietic stem cells with a novel retrovirus has allowed long-term expression of human Bcl-2 in multiple hematopoietic lineages. Thy-1.2lo Sca-1+ H-2Khi stem cells enriched from the bone marrow of 5-fluorouracil-treated (Ly5-2) mice were infected with the bcl-2 retrovirus and injected into (Ly5-1) irradiated recipients. Analysis at 5 months indicated that reconstitution of hematopoiesis occurred predominantly from donor-derived (Ly5-2+) stem cells and that, in half the mice (18 of 35), most blood cells derived from virally transduced stem cells. The level of Bcl-2 expression achieved with the retroviral vector approached that of a well-characterized transgenic vector and could be sustained for life in several blood cell lineages. In the 25 mice assessed at 10 months, human Bcl-2 was readily detectable in 62+/-22% of Ly5-2+ peripheral blood leukocytes. More detailed analysis of a cohort killed between 14 and 20 months established that human Bcl-2 protein could be detected in B and T lymphocytes, granulocytes, macrophages, and some immature erythroid cells. Furthermore, hematopoietic stem cells from the bone marrow of these mice maintained Bcl-2 expression in hematopoietic tissues of secondary recipients for at least another 19 months. These data provide clear evidence for efficient infection of primitive hematopoietic stem cells and for maintenance of proviral expression for over 2.5 years, the lifespan of mice. The level of exogenous Bcl-2 was sufficient to enhance survival of B and T lymphoid cells, granulocytes, and myeloid colony-forming cells cultured under suboptimal conditions, but hematopoiesis in the mice was not notably perturbed.

Animals↗

Results of treatment of primary breast carcinoma by radical radiotherapy with artificial pneumothorax.

One hundred and forty-three women with primary breast carcinoma were treated by radical radiotherapy associated with artificial pneumothorax to include the breast and lymphatics en bloc with large opposed fields. Surgery was restricted to local excision or drill biopsy. Most patients received a tumour dose of 5200-5600 cGy in 19-22 fractions over 4 weeks and were followed up for at least 5 years. Local control was achieved in 87% of T1, 52% of T2, 27% of T3 and 23% of T4 tumours. For T2 tumours local control was greater following excision biopsy (75%) than when surgery was more limited (21%). Acute morbidity was mostly minor and self-limiting. The commonest permanent late complication was restriction of shoulder movement in 20 patients. This method although safe and feasible does not offer significant advantages over conventional techniques.

Adult↗

Megestrol acetate in the treatment of advanced post-menopausal breast cancer.

The effect of megestrol acetate 160 mg daily was studied in 49 previously treated post-menopausal patients with advanced carcinoma of the breast. An overall response of 31% was obtained with 1 complete and 14 partial remissions, chiefly in soft tissue and bone. The median duration of response was in excess of 10 months. Toxicity was minimal and the only notable side effect was mild weight gain without fluid retention. Megestrol acetate is safe and well tolerated, with useful activity in the palliation of advanced breast cancer.

Aged↗

Disease-based assessment of peripheral vascular disease in nursing facility patients.

OBJECTIVE: To determine the frequency of diagnosis of peripheral vascular disease (PVD) and selected related conditions in patients in a nursing facility, to determine the frequency of patients with risk factor(s) for or clinical evidence of PVD but without a diagnosis of PVD or a related condition, and to determine the frequency with which patients with and without a diagnosis of PVD or a related condition were treated with drug and nondrug therapies. DESIGN: A multicenter, disease-based, retrospective evaluation. SETTING: 41 nursing facilities in 6 regions of the US. PATIENTS: 4038 patients in a nursing facility: 827 patients with a PVD or related diagnosis; 2719 patients without a PVD or related diagnosis but with risk factor(s) for or clinical evidence of PVD; and 492 patients without a PVD or related diagnosis, risk factor(s), and clinical evidence. MAIN OUTCOME MEASURES: Evidence of disease and drug therapy for PVD. RESULTS: PVD was documented in 21% of patients; another 67% had risk factor(s) for or clinical evidence of PVD but no diagnosis of PVD or a related condition. Pentoxifylline was prescribed for 3% of the total sample and 12% of patients with PVD or a related condition. CONCLUSIONS: PVD appears to be inadequately evaluated in patients in a nursing facility. Disease treatment strategies should be developed and implemented to educate healthcare professionals and the general public about the need to acknowledge, assess, and treat PVD and related conditions.

Adult↗