High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support.

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels

Vacuum-assisted abdominal wall lift for minimal-access surgery: a porcine model study.

Carbon dioxide pneumoperitoneum, although used universally in laparoscopy, has several well-documented complications and disadvantages. The authors describe a simple method of creating vacuum between a rigid shell and the abdominal wall in a porcine model to create adequate operative space for minimal-access surgery, which does not requires carbon dioxide, does not raise intraabdominal pressure, and is safe, cost effective, and feasible. The proposed device and method could be useful wherever basic laparoscopic equipment and a vacuum pump are available, including many parts of the developing world. The study was carried out with three groups using individual porcine models for each study. Group 1 was studied for feasibility of abdominal wall lift, adequacy of intraabdominal space, optimal vacuum levels, and safety and efficacy of the procedure. Group 2 was subjected to laparoscopic cholecystectomy and salpingectomy. Group 3 was studied for 2 days and 8 days after the animals were subjected to prolonged, high-level vacuum and monitored every 24 h to establish long-term effects. In all three groups the safety and efficacy of the proposed method were established, as well as the absence of physiological or histological alterations.

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na+,K+-adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 +/- 8.9; drug-treated, 86.9 +/- 4.9 mm Hg; p less than 0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 +/- 1.8; drug-treated, 5.2 +/- 0.4 mmol/L cells; p less than 0.002) and calcium (placebo, 13.5 +/- 1.6; drug-treated 10.8 +/- 3.3 mumol/L cells; p less than 0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+,K+-ATPase of erythrocyte membranes (placebo, 7.1 +/- 1.1 X 10(-2); drug-treated, 9.0 +/- 0.6 X 10(-2) microM inorganic phosphate/hr/mg; p less than 0.001) at the end of the study. However, no significant change in the ouabain-insensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx.(ABSTRACT TRUNCATED AT 250 WORDS)

Knotting of a bypass graft catheter: report of a case.

A case of knotting of a bypass graft catheter during coronary arteriography is presented. An arteriotomy had to be done to remove the catheter. A possible mechanism causing this complication and precautions to avoid it are described.

The small right coronary artery: angiographic implications--case reports.

Two patients with small right coronary arteries are presented. Possible complications during coronary angiography and methods of preventing them are discussed. It is stressed that the time of occlusion of the artery by the catheter tip should be kept to a minimum. The use of newly available angiographic catheters with side holes is also illustrated.

Severe pulmonary hypertension with patent ductus arteriosus.

A 36-year-old man was found to have severe pulmonary hypertension and a right-to-left shunt secondary to a patent ductus arteriosus. Attempt at surgical closure was unsuccessful. The patient was followed up for 21 years, and his only significant medical problem is leg weakness to moderate exertion.

Possible mechanism of interleukin-2-induced decline of serum cholesterol during adoptive cellular immunotherapy in cancer patients.

The serum levels of total, LDL, and HDL cholesterol of patients receiving intravenous infusion of interleukin-2 as part of adoptive cellular immunotherapy were analyzed. The total, LDL, and HDL cholesterol significantly decreased to about one-half of the pretreatment levels after 5 days of infusion (183 +/- 34 to 110 +/- 19, 112 +/- 40 to 48 +/- 24, and 41 +/- 10 to 16 +/- 7 mg/dl, respectively). The decrease was gradual during each day of the treatment. Lymphocyte concentration increased markedly during treatment (4.0 +/- 0.52 to 12.3 +/- 2.95 million cells/ml) and the low-density lipoprotein receptor levels in the lymphocytes also increased significantly (1188 +/- 240 to 1442 +/- 276 ng of bound LDL/million cells). The decrease in cholesterol levels may be related to the cholesterol needed for membrane synthesis during lymphocyte proliferation.

Hysteresis in the human RR-QT relationship during exercise and recovery.

The present study was undertaken to test the hypothesis that the human RR-QT relationship during dynamic exercise differs markedly from that during the recovery phase. Fourteen subjects from the age of 16 to 71 years exercised on a treadmill according to the Bruce protocol. Electrocardiograms were recorded continuously on a magnetic tape, from 1 minute before exercise to 10 minutes into recovery. An exponential formula, proposed by us earlier, closely represented the exercise RR-QT data. However, it was not appropriate for the often S-shaped recovery curves which invariably deviated from the exercise curves, exhibiting hysteresis. Initially, all recovery QT intervals were shorter than the exercise values, but later in the recovery, some crossed the exercise curves from below, resulting in longer QT intervals. The recovery data were fitted by a third degree polynomial, and the hysteresis was calculated as the area between the exercise and recovery curves within a 150 ms range of the RR interval starting from its minimum value. The mechanisms for the occurrence of hysteresis are likely to involve the sympatho-adrenal activity in the early post-exercise period and the time course of QT interval adaptation to rapid changes in the RR interval.

Effect of ethanol on regional myocardial blood flow and hemodynamics, before and after coronary artery ligation in dogs.

The effects on regional myocardial blood flows (RMBF) and hemodynamics due to ethanol administered before and after acute coronary artery ligation (CAL) in 18 anesthetized dogs were studied. Ethanol was administered to seven dogs (group I) prior to CAL and to six dogs (group II) after CAL; five dogs (group III, control) received only saline before and after CAL. Uniform blood ethanol levels (180 +/- 30 mg/dl) were maintained in groups I and II after initial ethanol administration. In these groups the heart rate and rate-pressure product (which reflects myocardial oxygen consumption) remained stable, but pulmonary arterial pressures were elevated. Other hemodynamic parameters remained stable in all groups. Ethanol caused a significant transmural increase of RMBF (p less than 0.001) in both groups I and II. In group II the increase was significant in both nonischemic and ischemic tissues, with no apparent redistribution of flow among the myocardial layers. The percentage increase of RMBF due to ethanol was highest in group II nonischemic tissue (95-107%) compared to the corresponding ischemic tissue (57-60%) and the group I myocardial tissue (36-47%) prior to CAL (p less than 0.001). The observed differences between ethanol pre- and posttreatments suggest different interactions between ethanol and catecholamines. The results also confirm that vasodilatory reserve is present in the acutely ischemic myocardium and that the local availability of ethanol is important for coronary vasodilatation.

Effect of propranolol on the QT intervals of normal individuals during exercise: a new method for studying interventions.

A new method was used to study the effect of a single dose of propranolol on the QT intervals during exercise in 11 normal volunteers. They exercised maximally on a bicycle ergometer and repeated the test after taking propranolol (40 mg) by mouth two hours before. Electrocardiograms were continuously recorded on magnetic tape and the cardiac cycle length (RR interval) and the QT interval were measured every five seconds by a computer aided method. The RR-QT data from each test during the exercise phase were analysed by an exponential formula, QT = A - B x exp (-k x RR) and by Bazett's formula, QT = K x square root of (RR). Three reference QT intervals, QTc1, QTc2, and QTc3, estimated at RR = 400, 700, and 1000 ms respectively from the regression curves of both formulas were compared. The exponential formula, which consistently gave a better fit with the data, showed that propranolol had a biphasic action on the QT intervals during exercise. It significantly prolonged the mean (SD) interval at longer cycle lengths (from 287 (27) to 305 (18) ms at RR = 1000 ms and shortened it at shorter cycle lengths (from 198 (14) to 179 (16) ms at RR = 400 ms). In contrast, Bazett's formula did not show any significant effect when the same raw data were used. The exponential formula can be adapted to study other interventions or conditions that affect QT intervals.