SummaryA total of 32 patients suffering from acute myeloid leukaemia were initially treated with daunorubicin and cytosine arabinoside, and eight who achieved full remission were given a brief cytoreduction course of cyclophosphamide and thioguanine. Of these eight patients seven were then actively immunized with 10' irradiated allogeneic acute myeloid leukaemia cells and B.C.G. at weekly intervals. Six of these patients have survived in apparent good health for more than one year. Bone marrow changes suggestive of relapse were used as an indication for further short courses of chemotherapy, and except on single occasions in two different patients clinical relapse has been prevented. The average duration of first (bone marrow) remission appears to be comparable with the best achieved in trials using regular chemotherapy for maintenance, though criteria for determining relapse may be different. The rate of reinduction of remissions (bone marrow) in this series was high, with a subsequent increase in overall survival time. Possible explanations for the high rate of reinduction include, firstly, the effects of active immunization with specific leukaemia antigen; secondly, non-specific adjuvant effect; thirdly, avoidance of drug resistance; and, fourthly, early diagnosis of relapse by frequent bone marrow examinations.
Metabolic balance studies were carried out in 17 unselected patients with acute myeloid leukaemia. Widespread metabolic disturbances were observed. Serum Na fell below 135 mmol/1 in 14 patients (82%) and 11 patients (64%) developed hypokalaemia. An increased osmolal clearance caused by a release of electrolyte and blast cell waste (i.e. urea, urate, etc.) during chemotherapy appeared to be the principle cause of natriuresis and hyperkaluria. Seven patients had proteinuria before and eight others developed it during antileukemic therapy. Nine patients (53%) developed proximal renal tubular dysfunction with aminoaciduria, hyperphosphaturia and incomplete reabsorption of urate. No significant relation was found between this widespread glomerulo-tubular dysfunction and lysozymuria. We suggest that antileukaemic drugs release unidentified substances from blast cells which are toxic to the kidney. Metabolic alkalosis in six patients (35%) was probably related to volume depletion and hypokalaemia, while two patients developed acidaemia with the onset of renal failure. Hypocalcemia in seven patients (41%) had a multifactorial basis: hyperphosphaturia, septicaemia, malnutrition and cytotoxic drugs were among the probable causes.
743uterine activity (Alexandria units) at varying doses of orciprenaline in seven patients studied for this effect is given in Table II. Tachyphylaxis was not observed in the three patients studied for 25, 70, and Maternal tachycardia and increase in pulse pressure were noted in all patients but presented no problems. The most unpleasant side effect was nausea and vomiting which occurred in three patients at the effective dose after 9, 20, and 22 minutes respectively. This may well limit the period of administration. Further clinical experience has shown that diazepam reduces this distressing symptom.Some difficulty was encountered in recording the fetal heart rate phonocardiographically at higher infusion rates. This was due to the transmission of abdominal aortic sounds when the maternal pulse pressure was markedly increased. The maternal aortic sounds then obscured the fetal heart sounds so that the maternal pulse rate was recorded instead. In these circumstances the fetal heart rate was auscultated in the usul manner without difficulty.
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