A phase I-II study of isolated hepatic perfusion using melphalan with or without tumor necrosis factor for patients with ocular melanoma metastatic to liver.

There are no satisfactory treatment options for patients with ocular melanoma metastatic to liver, and after liver metastases are identified, median survival is only between 2 and 7 months. Because liver metastases are the sole or life-limiting component of disease in the vast majority of patients who recur, we reasoned that complete vascular isolation and perfusion of the liver might result in clinically meaningful regression of disease. Between September 1994 and July 1999, 22 patients (13 women and 9 men; mean age, 49 years) with ocular melanoma metastatic to liver were treated with a 60-min hyperthermic isolated hepatic perfusion (IHP) using melphalan alone (1.5-2.5 mg/kg, n = 11) or with tumor necrosis factor (TNF, 1.0 mg, n = 11). Via a laparotomy, IHP inflow was via the hepatic artery alone (n = 17) or hepatic artery and portal vein (n = 5) and outflow from an isolated segment of inferior vena cava. Most patients had advanced tumor burden with a mean percentage of hepatic replacement of 25% (range, 10-75%) and a median number of metastatic nodules of 25 (range, 5 to >50). Complete vascular isolation was confirmed in all patients using a continuous intraoperative leak monitoring technique with 131I radiolabeled albumin. There was one treatment mortality (5%). The overall response rate in 21 patients was 62% including 2 radiographic complete responses (9.5%) and 11 partial responses (52%). The overall median duration of response was 9 months (range, 5-50) and was significantly longer in those treated with TNF than without (14 versus 6 months, respectively; P = 0.04). Overall median survival in 22 patients was 11 months. These data indicate that a single 60-min IHP can result in significant regression of advanced hepatic metastases from ocular melanoma. TNF appears to significantly prolong the duration of response.

Desmopressin acetate in cardiac surgery: a double-blind, randomized study.

Use of desmopressin acetate (DDAVP) for patients having cardiac surgery is controversial. We did a double-blind, randomized study of 83 patients having cardiac operations at Georgetown University Hospital. The effect of DDAVP on bleeding as compared to placebo was evaluated by blood loss, replacement volume, and laboratory tests. There were no significant differences in baseline and intraoperative data between the DDAVP (n = 40) and placebo (n = 43) groups. Total drainage for the first 24 postoperative hours was 1,214 mL (+/- 78) for the DDAVP group and 1,386 mL (+/- 116) for the placebo group (not significant). There were no significant differences in replacement therapy. In this study, administration of DDAVP did not decrease bleeding.

The resting volume and compliance characteristics of the bronchial cuff of left polyvinyl chloride double-lumen endobronchial tubes.

The resting volume of a low-pressure, high-volume cuff is an important factor that determines the cuff compliance, because it is the maximum volume that maintains the low-pressure characteristics of the cuff. Modern polyvinyl chloride (PVC) double-lumen tubes (DLT) are designed with a low-pressure bronchial cuff to minimize the risk of bronchial damage. Maintenance of the low-pressure characteristics of this cuff, however, requires knowledge of how its resting volume and compliance vary between different DLT sizes and brands, and how the compliance changes when the cuff is inflated inside different-sized bronchi. We, therefore, measured the bronchial cuff pressure-volume relationship for each of the adult sizes, 35 Fr, 37 Fr, 39 Fr, and 41 Fr, of the Mallinckrodt, Sheridan, Rusch, and Portex left DLTs. The compliance of each cuff was characterized by: 1) the cuff resting volume, defined as the smallest cuff volume beyond which a 0.5-mL increase in volume resulted in more than 10 mm Hg increase in cuff pressure; and 2) the cuff pressure at 3-mL volume. Measurements were repeated for sizes 35 Fr and 41 Fr left Mallinckrodt DLTs with the bronchial cuff lying inside two canine left main-stem bronchi measuring 11 mm and 13 mm in diameter. The bronchial cuff resting volume ranged from 1.5 to 5.0 mL in different sizes and brands of DLTs, which could be explained by differences in cuff size between different manufacturers and between different DLT sizes of the same manufacturer.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence that cocaine slows cardiac conduction by an action on both AV nodal and His-Purkinje tissue in the dog.

The effects of intravenous cocaine (2 mg/kg) were tested on several indices of cardiac electrical activity in sedated dogs. These included sinus rate, PR, AH, and HV intervals; AV nodal effective refractory period (AVNERP); ventricular effective refractory period; QRS duration; and the QT interval. Cocaine induced significant changes in six control animals with an intact-functioning autonomic nervous systems. After pharmacologic autonomic blockade with propranolol plus propantheline, cocaine increased the PR interval (+ 11 +/- 4.0 ms, p less than 0.05), primarily by slowing conduction at the AV nodal level. However, with constant atrial pacing at a rate above the sinus cycle length, prolongation of both the AH and the HV intervals (+ 15 +/- 2.5 and 6.7 +/- 1.7 ms, respectively) occurred. There was also a significant increase in the AVNERP (+ 29 +/- 5.9 ms, p less than 0.05). Consistent with the observed rate-dependent HV prolongation, cocaine decreased the rate of rise of phase 0 of the transmembrane action potential of Purkinje fibers. These data indicate that cocaine impairs cardiac conduction by direct actions on AV nodal and His-Purkinje cells.

Factors determining whether cocaine will potentiate the cardiac effects of neurally released norepinephrine.

The purpose of the present study was to re-evaluate the effects of cocaine on cardiac responses elicited by sympathetic nerve stimulation. Cats anesthetized with pentobarbital and subjected to spinal cord transection were used. Control heart rate increases were obtained to submaximal stimulation of postganglionic accelerator nerves, before and after i.v. bolus doses of cocaine ranging from 0.0625 to 2.0 mg/kg. Maximal potentiation of heart rate increases elicited by nerve stimulation were observed with 0.25 mg/kg. In precocaine controls, stimulation increased sinus rate by 31 +/- beats/min; 30 sec to 1 min after cocaine (0.25 mg/kg), stimulation increased sinus rate by 55 +/- beats/min. Maximal potentiation (80 +/- 10%) was observed at 30 sec to 1 min after cocaine administration, and was usually over by 45 to 60 min later. Cocaine was repeated twice (0.25 mg/kg i.v.) at hourly intervals and the magnitude of potentiation was only 19 +/- 6 and 24 +/- 4%, respectively, indicating that tachyphylaxis had developed toward cocaine's potentiating effect. Dose-response studies indicated that as little as 0.0625 mg/kg of cocaine can potentiate heart rate increases elicited by sympathetic nerve stimulation. Doubling the dose to 0.125 mg/kg, and again to 0.25 mg/kg, resulted in a linear dose-related increase in the magnitude of potentiation. However, doubling the dose again to 0.5 mg/kg and increasing this dose by 4-fold to 2 mg/kg did not result in additional potentiation. Indeed, there was a significant drop-off in the magnitude of potentiation to nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer.

Risk factors for local-regional recurrence of breast cancer were analyzed in a retrospective review of 117 patients treated with adjuvant CMF (Cytoxan [Mead Johnson & Co, Evansville, Ind], methotrexate, 5-fluorouracil) after radical or modified radical mastectomy at the Vincent T. Lombardi Comprehensive Cancer Center (Washington, DC). The median follow-up time was 50 months after mastectomy. The median time to recurrence was 23 months. The actuarial local-regional failure rate was 19% at five years. Risk of local failure correlated with size of primary (27% for T3 v 15% for T1) and axillary node status (36% for four or more positive nodes v 9% for three or fewer positive nodes). These findings suggest a rationale for the addition of postoperative radiation therapy in high-risk patients treated with adjuvant chemotherapy.