Clinical Studies with Vincristine

Forty patients with malignant neoplastic disease received vincristine in aneffort to define the toxicity, the tolerated dose, the effect of varying doseschedules, and the antitumor properties. The toxicity of vincristine is doserelated, and the tolerated dose for the weekly schedule is 0.05 mg. per Kg.for the majority of patients. The tolerated dose per unit time is independentof the schedule of administration. The toxic manifestations relate primarilyto the neuromuscular system and the gastrointestinal tract. At the tolerateddose or below, these manifestations are reversible and not accumulative.Hematologic toxicity is rare, and thrombocytosis occurs in some patients.Vincristine produces tumor regression in the majority of the patients withlymphoma where its activity compares favorably with that of the alkylatingagents and vinblastine. There is suggestive evidence that cross-resistance between vincristine and the alkylating agents and between vincristine and vinblastine does not occur.

Accepted on December 28, 1962     

Echocardiographic Diagnosis of a Partially Thrombosed Right Coronary Artery Aneurysm in a Patient with Polycystic Disease

This report describes a patient with polycystic disease of the kidneys and the liver and an aneurysm of the proximal right coronary artery. Transthoracic and transesophageal echocardiographic imaging showed a 5 times 5 cm oval-shaped, spherical tumor in the atrioventricular corner. The tumor was partially filled with homogenous echostructures. Coronary angiography showed aneurysmatic configuration of the right coronary artery, but no region demonstrating a mass of similar size and shape as seen by echocardiography. The finding of a partially thrombosed coronary artery aneurysm was subsequently confirmed by surgery.     

IS THE END-TIDAL PARTIAL PRESSURE OF ISOFLURANE A GOOD PREDICTOR OF ITS ARTERIAL PARTIAL PRESSURE?

End-tidal partial pressure of isoflurane (PE'_iso) may be usedas a measure of anaesthetic depth. During uptake, an arterialpartial pressure (Pa_iso) which is considerably less than PE'_iso(Pa_iso/PE'_iso«1)leads to underestimation of depth of anaesthesia and, duringelimination, PE'_iso/Pa_iso«1 will lead to an overestimationof anaesthetic depth. We measured Pa_iso/PE'_iso during a 60-minuptake period of 1% isoflurane and PE'_iso/Pa_iso during the subsequent60-min elimination period in 26 patients (age 13–88 yr,ASA I–III) undergoing various surgical procedures. After15 min of isoflurane uptake, Pa_iso/PE'_iso of 26 patients wasmean 0.78 (SD 0.10) and this increased only marginally at 60min (0.79 (0.09)), whereas during elimination, PE'_iso/Pa_isowas in the range 0.79 (0.14)–0.83 (0.11). Predictabilityof Pa_iso in a given patient is hindered by the high SD of Pa_iso/PE'_isoand PE'_iso/Pa_iso, but it may be improved by taking into accountage, ASA physical status category, vital capacity, inspiredminus end-tidal isoflurane partial pressure and arterial minusend-tidal carbon dioxide partial pressure during uptake; andobesity, end-tidal isoflurane partial pressure and arterialminus end-tidal carbon dioxide partial pressure during elimination.However, even with multiple regression analysis (to accountfor the various possible variables), clinically useful predictionof Pa_iso/PE'_iso and PE'_iso/Pa_iso in a particular patient isnot possible (residual SD 0.084 and 0.113, respectively).     

Evaluation of a New Chemotherapeutic Agent in Patients with "Advanced Refractory" Acute Leukemia. Studies of 6-Azauracil

6-Azauracil was studied in patients with "advanced" acute leukemia, refractory to standard chemotherapy. Under the conditions of the study thiscompound was found to have no significant antileukemic activity. As a result,these data have defined the natural history of this phase of acute leukemia. Asignificant proportion (30 per cent) of these patients showed objective hematologic improvement even in the absence of effective specific therapy, whichmight be ascribed to a prospective new agent. The median survival from theonset of the study of this group of patients was two months, and survivalpatterns for adults and children were similar.

Submitted on December 23, 1959 Accepted on February 20, 1960