No abstract

Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5·6 to 27 min resulted in a decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 niM 2‐deoxyglucose, 10−3 i.u. insulin ml−1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2‐deoxyglucose but increased by insulin. 2‐Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.

I The sensitivities of alloxan and streptozotocin diabetic and hereditary obese pithed rats to acetylcholine, isoprenaline and noradrenaline were compared to those of controls. 2 Blood pressure and heart rate recordings made before dosing was started showed the streptozotocin-treated animals to have a significantly reduced heart rate and increased pulse pressure as compared with controls.3 Both diabetic groups were found to have reduced sensitivities to the pressor effect of noradrenaline, the depressor effect of acetylcholine, the positive chronotropic and inotropic effect of isoprenaline and the reduction in diastolic pressure induced by isoprenaline. The reduction in sensitivity was generally much greater in the streptozotocin diabetic animals. 4 The genetically obese rats were found to have similar sensitivities to all three agents as did their non-obese litter mates. 5When either diabetic group was deprived of food for 24 h preceding the tests the sensitivities were found to be raised significantly towards normal in almost all cases. 6 The results are contrasted with previous in vitro results and possible causative metabolic factors discussed. It is suggested that sensitivity changes are unevenly distributed within the cardiovascular system.

Eleven patients with advanced soft tissue sarcoma were treated with whole body hyperthermia (41.8°C–43.0°C) for 2 hours, doxorubicin (45 mg/m2) at the beginning of peak temperature and cyclophosphamide (1000 mg/m2) 6 hours after doxorubicin. Warming was accomplished with a nylon and vinyl mesh water perfused suit and heating blankets under barbiturate anesthesia. Thirty‐five thermochemotherapy treatments were administered after an initial baseline euthermic course. There were two complete and two partial responses including three of three liposarcomas and one of two leiomyosarcomas, and there were two disease stabilizations. Morbidity included anasarca, nausea and vomiting, diarrhea, myalgias, mild surface burns, perioral herpes simplex, reversible neuropathy, hypotension, and cardiac arrythmias. Hyperglycemia and hypophosphatemia were found during heating, and normalized at 24 hours. Liver enzyme elevations occurred 24 hours after heating and normalized within 1 week. A uniform platelet decrease (mean, 107,000/μ l) was found at 24 hours. Thermochemotherapy was found to be a feasible approach for selected patients with advanced soft tissue sarcoma for the subset of liposarcomas and leiomyosarcomas.

Isotopes of water (deuterium oxide and tritium oxide) have been used for the determination of total body water in certain mammalian species (Hevesy & Hofer, 1934;Pace, Kline, Schackman & Harfenist, 1947; Soberman, Brodie, Levy, Axelrod, Hollander & Steele, 1949;Haigh & Schnieden, 1956;Langham, Eversole, Hayes & Trujillo, 1956; Fallot, Aeberhardt & Masson, 1957). However, the techniques involved in these determinations have limited use, being either difficult, expensive or timeconsuming. Recent advances in scintillation counting techniques (Haigh, 1957) have made it much easier to estimate one of these isotopes of hydrogen, namely tritium. The purpose of the present paper is to describe how far such scintillation counter techniques can be applied to the determination of tritium in urine and plasma and the estimation of degree of error involved. The use of such techniques for a comparative study of total body water in a number of mammalian species and of water turnover under tropical conditions in one species, namely man, is also presented. METHODS 0-5 ml. of tritiated water or processed tritiated plasma or urine (see below) was added to 8 ml. of absolute ethanol and 10 ml. of scintillation solution (3 g 2:5-diphenyloxazole/l. sulphur-free toluene). The mixture was shaken and then centrifuged at approximately 1500 rev/min for 2-3 min. 5 ml. of the supernatant fluid was placed in the special counting container supplied with the N612 Ekco Scintillation Counter. This scintillation unit was kept at -20°C in a deep-freeze cabinet and its amplifier set at maximum gain. It was connected to a N 530E Ekco Automatic Scaler unit which was set at H.V. 1200 and Discrimator bias of -5 V. The scaler received a stabilized current from a constant-voltage stabilizer (Servomex AC 2 Mark IIB). Unless otherwise stated, all specimens were counted for 1000 sec and were allowed to cool in their counting containers for 1000 sec at -20°C before counting.Preparation of urine. 3*5 ml. of urine was mixed thoroughly in a test-tube with 0 5 g of activated charcoal. The resultant sludge was filtered through a Whatman No. 2 filter paper and 0 5 ml. of the filtrate was then added to 18 ml. of the alcohol-scintillator mixture, shaken and centrifuged, and a 5 ml. portion taken for counting. J. M. FOY AND H. SCHNIEDENPreparation of rat, cat, guinea-pig or rabbit plasma. 0*5 ml. of plasma was added to 18 ml. of the alcohol-scintillator solution mixture. After thorough shaking the mixture was centrifuged. 5 ml. of the clear supernatant fluid was then withdrawn and placed in the counting container before counting.Preparation of human plasma. Since it was found that the above method of preparation for rat plasma gave a coloured (orange-yellow) supernatant liquid with human and baboon plasma, another method was also investigated. The plasma was precipitated with 10 % trichloroacetic acid (Langham et al. 1956) and 0 5 ml. of the clear colourless filtrate was mixed with 18 ml. of alcohol-scintillation fluid mixture. 5 ml. of this final mixture was used f...