Browsing The Christie Research Publications Repository by Title
Now showing items 1-20 of 7985
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1 versus 2-cm excision margins for pT2-pT4 primary cutaneous melanoma (MelMarT): a feasibility study.There is a lack of consensus regarding optimal surgical excision margins for primary cutaneous melanoma > 1 mm in Breslow thickness (BT). A narrower surgical margin is expected to be associated with lower morbidity, improved quality of life (QoL), and reduced cost. We report the results of a pilot international study (MelMarT) comparing a 1 versus 2-cm surgical margin for patients with primary melanoma > 1 mm in BT.
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11 beta-Hydroxysteroid dehydrogenase activity in Cushing's syndrome: explaining the mineralocorticoid excess state of the ectopic adrenocorticotropin syndrome.A characteristic feature of the ectopic ACTH syndrome is a state of mineralocorticoid excess, although the etiology remains obscure. Some forms of endocrine hypertension, such as licorice ingestion, have been explained by cortisol acting as a mineralocorticoid in the setting of inhibition or deficiency of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD). This enzyme is responsible for the conversion of cortisol (F) to hormonally inactive cortisone, and its activity in vivo can be inferred from the ratio of the urinary excretion of tetrahydrocortisol (THF) and its isomer (5 alpha THF) to tetrahydrocortisone. Twenty-two patients with Cushing's syndrome (11 pituitary dependent, 9 ectopic, and 2 adrenal adenomas) and 13 controls were studied. Compared to controls. Cushing's patients had a significant increase (P < 0.001) in the excretion of all principal metabolites of F, secondary to a 5- to 6-fold increase in the cortisol secretion rate [median, 34.0 (range, 13.3-327) mg/day in Cushing's vs. 6.1 (range, 2.5-10.3) mg/day in controls]. The THF plus 5 alpha THF/tetrahydrocortisone ratio was significantly increased in Cushing's syndrome regardless of etiology [mean, 1.81 (range, 1.09-9.99) in Cushing's vs. 0.81 (range, 0.51-1.47) in controls; P < 0.001), indicative of defective 11 beta HSD activity. Furthermore, compared to patients with pituitary-dependent Cushing's, this ratio was significantly higher in patients with the ectopic ACTH syndrome (4.12 vs. 1.49; P < 0.01) and was inversely correlated with serum potassium levels (r = -0.57; P = 0.01; n = 22). One explanation for the mineralocorticoid excess state of the ectopic ACTH syndrome appears to be that cortisol gains inappropriate access to the mineralocorticoid receptor through failure of its normal metabolism by 11 beta HSD. The reason for the defective 11 beta HSD activity is unclear, but it may be secondary to substrate saturation, inhibition by other adrenal steroids, or product inhibition.
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11-week course of sequential methotrexate, thoracic irradiation, and moderate-dose cyclophosphamide for "limited"-stage small-cell bronchogenic carcinoma. A study from the Manchester Lung Tumour Group.55 patients with inoperable but "limited"-stage small-cell carcinoma were treated sequentially with methotrexate, radiotherapy, and high doses of cyclophosphamide. The treatment was completed over 11 weeks and no maintenance chemotherapy was given. Follow-up lasted 9-29 months. Toxicity was acceptable, despite doses of cyclophosphamide of 1.5-3.5 g/m2. The complete response rate was 53%. Median survival for the total patient group was 12 months, range 2-29+. Patients who attained a complete response had a 17 month median survival; 17 patients remained in complete remission, 9 of whom first underwent treatment 14-29 months previously. Karnofsky performance scores improved after treatment and most patients were able to resume normal activity. The results are similar to those obtained with prolonged combination chemotherapy.
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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.
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118 Multiparametric Cardiovascular Magnetic Resonance Surveillance of Acute Cardiac Allograft Rejection and Characterisation of Transplantation-associated Myocardial Injury.Acute cardiac allograft rejection (ACAR) affects approximately 20% of patients in the first year post-transplantation, represents a leading cause of death during this period and confers higher mortality in patients surviving beyond the first year. Clinical features of ACAR are unreliable, therefore serial surveillance endomyocardial biopsies are performed in order to detect ACAR at an early stage. However the procedure is invasive, is associated with uncommon but significant complications and expensive, factors which prevent more frequent monitoring thus limiting optimal immunosuppression titration. This study aimed to prospectively and longitudinally evaluate the performance of multiparametric cardiovascular magnetic resonance (CMR) for detecting and monitoring ACAR in the early phase post-transplant, and characterise graft recovery following transplantation.