The effect of smoking on the heart has been a controversial subject. The present studies were undertaken to investigate the effect of cigarette smoking on the coronary flow, myocardial usage of oxygen and myocardial extraction of glucose, pyruvate, lactate, and ketones. Catheterization of the coronary sinus revealed that cigarette smoking in patients without heart disease results in a significant rise in coronary blood flow and heart rate and a significant (Icelilie in coronary vascular resistance and myocardial extraction of oxygen Despite these generally accepted actiolls ons specific tissue, the effect of smoking on the heart has been a controversial subject. The experimental literature on the effect of nicotine on animal and heart-lung preparations is contradictory. In 1912 Meyer,8

Continuous flow apneic ventilation (CFAV) was studied in five adult female patients. After induction of anesthesia with thiopental sodium (5 mg/kg) and fentanyl (5 micrograms/kg), and paralysis with pancuronium bromide (0.12 mg/kg), the patients were ventilated with oxygen at an FIO2 of 1.0 by face mask. Two polyethylene catheters (outside diameter [OD] 2.5 mm) were each inserted into the right and left mainstem bronchi. Each catheter had a curved tip measuring 2 cm in length. The angulation of the catheter tip from the axis was 20 degrees for the right side and 30 degrees for the left side. The endobronchial position was checked by fiberoptic bronchoscopy. Subsequently, tracheal intubation was performed using a 7.5 mm OD tracheal tube. CFAV was started when both catheters were connected to the gas delivery system. Humidified oxygen was delivered at total flows between 0.6 and 0.7 1/min. Arterial blood gases were analyzed every 5 min for 30 min. Monitoring included electrocardiogram, indirect blood pressure, heart rate, temperature, and peripheral nerve stimulation. Adequate oxygenation was maintained in all patients, 39.76 +/- 4.32 kPa (299 +/- 37 mmHg) at 30 min. There was a significant rise in Paco2 (P less than 0.05) at 30 min compared to the control, 4.92 +/- 0.25 kPa compared to 7.30 +/- 0.53 kPa (37.0 +/- 1.9 mmHg compared to 54.9 +/- 4.0 mmHg). There was a mean rise in Paco2 of 0.03 kPa/min (0.6 mmHg/min) compared to 0.5 kPa/min (3.8 mmHg/min) with apneic diffusion ventilation. In one patient there was no increase in Paco2 during the 30 min of CFAV.(ABSTRACT TRUNCATED AT 250 WORDS)

FMAU (1-[2'-deoxy-2'-fluoro-1-beta-D-arabinofuranosyl]-5-methyluracil) a newly synthesized fluorinated nucleoside, has potent in vitro antiviral and antileukemic activity and is active in murine leukemia lines resistant to cytosine arabinoside. In the initial phase I trial neurotoxicity, characterized by extrapyramidal dysfunction, was found to be the dose-limiting toxic effect, and a dosage of 32 mg/m2/day for 5 days was suggested for phase II studies. We report a second phase I study of FMAU using this schedule. Mild, transient neurologic dysfunction was encountered in patients treated at the starting dose of 4 mg/m2/day x 5 days and became severe and irreversible in two patients who received the highest cumulative doses administered at the 8 mg/m2/day x 5 days level. Both severely affected patients died. Severe neurotoxicity developed and progressed in these patients despite serial neurologic examinations, including detailed neuropsychologic tests implemented in an effort to detect early neurotoxicity. Because of these findings, further study of this drug as an antileukemic agent cannot be recommended. If it is to be used as an antiviral agent, further phase I study at lower doses is advised.