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Biomedical subjects

J L Toy

Publications and source records attributed to J L Toy.

9 recordsLinked to original sources

Response of differentiated but not anaplastic teratoma to interferon.

A Phase 2 trial was conducted using intramuscular lymphoblastoid interferon (IFN, Wellcome Research Laboratories), 4 MU per day, in 10 patients with chemotherapy-resistant teratomas. There was stabilisation of disease in 2 patients both of whom were in retrospect considered to have had differentiated teratoma at the time of IFN administration. There was progression of presumed active anaplastic germ cell tumour in 8 patients. One of these patients, a 15-year-old boy with biopsy proven differentiated teratoma has received 2 courses of lymphoblastoid IFN and 1 course of recombinant leukocyte A IFN (Roche Products Ltd.) lasting 5 1/2, 8 and 8+ months respectively. He has had a mixed response in his differentiated tumour which on each occasion has been maintained for the duration that he received IFN. Rising HCG levels during his second course of interferon required additional cytotoxic chemotherapy. Lymphoblastoid IFN does not appear to be active against anaplastic germ cell tumours but both lymphoblastoid and recombinant leukocyte A IFN may be useful in the treatment of unresectable differentiated teratoma.

Adolescent

The interferons.

An overview of the interferons is presented. A description of something of what is known about them is given, including: their genes; their protein structures and characteristics; their mechanisms of actions; and their varied biological effects emphasising particularly their immunomodulatory actions. Finally, a brief summary is made of the current status of human clinical studies that have been conducted with interferons in the oncological and viral fields, mentioning also recent findings in patients who have the acquired immunodeficiency syndrome (AIDS).

Animals

Coagulation studies in rheumatic heart disease.

The clotting characteristics of pulmonary and systemic blood were studied in 10 patients with chronic rheumatic mitral valve disease complicated by atrial fibrillation and in seven patients with aortic valve disease in sinus rhythm. A haemostatic basis for the association of rheumatic mitral valve disease with thrombotic emboli was sought. Both groups of patients showed differences in platelet function between pulmonary and systemic arterial blood. In patients with mitral valve disease aggregation of platelets was significantly greater in pulmonary than in systemic arterial blood at rest; the converse was true during exercise. In aortic valve disease platelet aggregation was greater in systemic than in pulmonary arterial blood at all times. Only the patients with mitral valve disease showed changes in blood coagulation during passage through the lungs and left heart; there was a small but statistically significant shortening in partial thromboplastin time in systemic as compared with pulmonary arterial blood both at rest and during exercise. Similarly, the effects of exercise on the various haemostatic factors measured were largely confined to the patients with mitral valve disease; in these patients exercise stimulated an increase in factor VIII in pulmonary arterial blood and an increase in platelet adhesiveness and aggregability in left heart blood. These changes provide a basis for the suggestion that in patients with rheumatic mitral valve disease, unlike those with aortic valve disease, there is an increased thrombotic tendency in blood in the left heart which is particularly pronounced during exercise.

Aortic Valve

The comparative effects of a synthetic and a 'natural' oestrogen on the haemostatic mechanism in patients with primary amenorrhoea.

A synthetic and a natural oestrogen were administered alternately for three months to nine women with primary amenorrhoea using a randomized cross-over schedule. Measurements of haemostatic function were performed before and at the end of each treatment period. No significant change in haemostatic function was observed after treatment with the 'natural' oestrogen, oestriol succinate. In contrast, treatment with a synthetic oestrogen, ethinyloestradiol, caused shortening of the prothrombin time and an increase in plasma concentration of factor VII and plasminogen. These data support other observations in suggesting that natural oestrogens may have fewer potentially adverse effects on haemostatic function than synthetic oestrogen.

Adolescent

The effects of long-term therapy with oestriol succinate on the haemostatic mechanism in postmenopausal women.

In a previous report we showed that oestriol succinate administered to postmenopausal women caused fewer changes in haemostatic function over a four-month period than ethinyloestradiol. Potential longer-term effects were studied in postmenopausal women treated for osteoporosis with oestriol succinate for up to 12 months. Over this period there was no significant change in concentration of plasma coagulation factors, an increase in plasminogen concentration and euglobulin lysis activity, and an inconsistent increase in platelet sensitivity to aggregation induced by ADP and collagen. The relative lack of effect of oestriol succinate on coagulation function is encouraging with regard to the future incidence of thromboembolic complications of therapy.

Adult

The effect of immunotherapy on survival of patients with acute myelogenous leukaemia after relapse.

A randomized controlled clinical trial for the use of immunotherapy for maintaining patients with acute myelogenous leukaemia has been conducted involving 52 patients. All patients received short pulsed maintenance chemotherapy but 30 of the patients received additional immunotherapy consisting of BCG and irradiated allogeneic myeloblastic leukaemia cells. Of the 22 patients who received chemotherapy alone, 19 died with a medium survival of 39 weeks, whereas 20 of the 30 patients who received chemotherapy plus immunotherapy died with an estimated median survival of 74 weeks. The value for the significance of the difference in death rates of patients was less than .01. The main effect of this immunotherapy was, however, due to a prolongation of survival after the patients had relapsed; the median survival for the immunotherapy patients being 23 weeks compared with only 11 weeks for the chemotherapy alone patients (p less than .005). The overall results also show that there was a slight prolongation of first remission in patients who received immunotherapy with a median duration of 44 weeks compared with 27 weeks for patients who received only chemotherapy. The possible mechanisms of action of this form of immunotherapy are discussed.

Adolescent