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Biomedical subjects

M Drayson

Publications and source records attributed to M Drayson.

6 recordsLinked to original sources

Myasthenia gravis and elderly people.

Myasthenia gravis is probably commoner than previously suspected, the annual incidence being nearer 9-10/million than earlier figures of 2-4/million. The current study found an annual incidence in Croyden of 9.1 per million (95% confidence limits 5.7-13.8 per million). Of the 22 patients (59%) seen in Croyden with newly diagnosed myasthenia gravis during the past 7 years, 13 were aged over 60. In a separate study of the age distribution of positive acetylcholine receptor antibody assays, 51% were 60 years or above in 1991, and 64% in 1994. The peak age in both sexes was 70-80, and numbers were greatest in men aged 60-80.

Adolescent

Multiple myeloma.

Multiple myeloma occurs in over 2000 new patients in England and Wales each year. It presents most frequently as bone pain and patients tend to become dehydrated and may develop renal failure. No available treatment is curative, but about two thirds of patients achieve a stable response with low dose combination chemotherapy. Combination chemotherapy including doxorubicin and carmustine with the alkylating agents cyclophosphamide and melphalan achieve a higher stable response rate than conventional treatment with melphalan and prednisone without additional haematological toxicity. These responses are associated with loss of bone pain and patients remain symptom free for months without further treatment. Relapse occurs on average in a little under two years and, though second responses are frequently obtained, the disease eventually becomes refractory. This paper looks at who should be treated and the benefits that may be expected from the treatments available.

Antineoplastic Combined Chemotherapy Protocols

Circulating soluble adhesion molecules in systemic vasculitis.

The plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin (sE-selectin), and vascular cell adhesion molecule-1 (sVCAM-1), might reflect endothelial activation and injury and would therefore be useful markers of disease activity in vasculitis. To investigate this we measured the levels of sICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in the plasma of patients with (a) active vasculitis (n = 16), (b) vasculitis in remission (n = 15), (c) chronic renal failure (CRF) (n = 10), and (d) normal healthy controls (n = 10). Plasma sICAM-1 levels were significantly higher in patients with active vasculitis, 323 ng/ml (193-607) compared with patients with inactive vasculitis, 199 ng/ml (131-297); P = 0.0006 and healthy controls, 188 ng/ml (138-259); P = 0.0002. Plasma sE-selectin levels were also significantly higher in the patients with active vasculitis, 45 ng/ml (15-65) compared with patients with inactive vasculitis, 25 ng/ml (15-55); P = 0.027 but not when compared with healthy controls, 35 ng/ml (20-55); P = 0.16. There was no difference in plasma sVCAM-1 levels between patients with active vasculitis, OD 0.56 (0.45-0.85) and inactive disease, OD 0.58 (0.47-0.79) (P = 0.12) or with healthy controls OD 0.49 (0.42-0.68) (P = 0.48). There were no significant differences between the plasma levels of any of the soluble adhesion molecules between patients with active vasculitis and patients with chronic failure.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Reactive Protein

Metabolism of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 by blood derived macrophages from a patient with alveolar rhabdomyosarcoma during short-term culture and 1 alpha,25-dihydroxyvitamin D3 after long-term culture.

We have examined the ability of blood-derived monocytes and macrophages isolated from a patient with alveolar rhabdomyosarcoma and hypercalcaemia, to form 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) or 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) from 25-hydroxyvitamin D3 (25(OH)D3). Adherent monocyte-macrophage cells incubated with 25(OH)D3 over the initial 2 days in culture synthesized 1.9 pmol 24,25(OH)2D3/h/incubation (representing 0.63 pmol/h/10(6) cells), whereas macrophages synthesized 1.03 and 1.15 pmol 1 alpha,25(OH)2D3/h/incubation after 1 and 4 weeks in culture respectively. In a further experiment synthesis of 1 alpha,25(OH)2D3 by long-term cultured macrophages fell from 2.25 to 0.04 pmol/h/incubation following exposure to 10 nM 1 alpha,25(OH)2D3 for 7 days, whereas 24,25(OH)2D3 synthesis was induced (0.46 pmol/h/incubation). The vitamin D3 metabolites were identified by co-chromatography with authentic 24,25(OH)2D3 or 1 alpha,25(OH)2D3 in three different high-performance liquid chromatography systems. Serum 1 alpha,25(OH)2D3 in the patient was markedly suppressed at 5 pg/ml (normal 20-50 pg/ml) indicating that raised 1 alpha,25(OH)2D3 was not the cause of the hypercalcaemia, but rather, that raised calcium may have suppressed renal 1 alpha,25(OH)2D3 synthesis. Administration of APD (3-amino-1-hydroxypropylidine-1,1-bisphosphonate) corrected the hypercalcaemia in the patient suggesting that increased bone resorption was responsible for the raised calcium. The results of this study show for the first time that immature blood derived monocyte-macrophage cells can synthesize 24,25(OH)2D3 before they mature into macrophages able to synthesize 1 alpha,25(OH)2D3.

24,25-Dihydroxyvitamin D 3

114Inm oxine-labelled lymphocytes--therapeutic applications.

It has shown that, after intravenous administration of autologous lymphocytes labelled with the beta-emitting radionuclide 114Inm, the cells initially migrate normally before succumbing to the toxic effects of the radiation. The radioactive material is then released from the cell and taken up by neighbouring radioresistant macrophages, thereby localizing a field of radiation to the site of lymphocyte death. Using this technique, lymphocytopoenia has been produced in rats. We have measured the whole-body distribution and excretion of radioactivity in patients who received escalating activities of 114Inm-labelled lymphocytes. All patients had active non-Hodgkin's lymphoma involving the spleen and liver which proved resistant to combination chemotherapy and conventional radiotherapy. Following intravenous administration, the labelled cells cleared rapidly from the vasculature with only 15% remaining in the peripheral blood at 30 min. The radioactivity continued to fall over the next 5 days to approximately 3% and was maintained at approximately 2% for up to 90 days. There was an almost immediate uptake of radioactivity by the spleen and liver which reached approximately 85% of the injected dose by 48 h. The localization of radioactivity stabilized by 48 h and thereafter the whole-body content fell by approximately 0.8% per day. Up to 5% of the administered radioactivity accumulated in the bone marrow. The activities administered were too low to produce a therapeutic response and no toxicity was experienced by the patients. A therapeutic study at higher activities is now underway.

Humans

The behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy.

It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that 114mIn deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.

Adult