Cardiotoxicity evaluation in patients treated with a mitoxantrone combination as adjuvant chemotherapy for breast cancer.

Indices of cardiac function were measured in 49 women who received adjuvant treatment for stage II breast cancer. The combination chemotherapy consisted of six monthly courses of cyclophosphamide, 500 mg/m2, mitoxantrone, 10 mg/m2 and fluorouracil, 500 mg/m2 (CNF). Left ventricular function was assessed by echocardiography, systolic time intervals and nuclear angiography. The values of the echocardiographic left ventricular end diastolic diameter (Dd) and end systolic diameter (Ds), and those of the index of preejection period (PEPI) and the ratio of the preejection period to left ventricular ejection time (PEP/LVET), determined in 41 patients before chemotherapy, at midcourse and after chemotherapy by echocardiography and systolic time intervals (STI), showed a slight but significant increase. All these values remained within normal limits. Resting nuclear angiography, performed before and after treatment, showed a decrease in LVEF by 10% or more in four patients; the postchemotherapy values remained within the normal range in all cases. In conclusion, adjuvant treatment of breast cancer patients with 6 cycles of the CNF combination, as judged by its effect on the measured indices, does not appear to be cardiotoxic.     

The effect of dopamine on renal function during aortic cross clamping.

Eighteen male patients undergoing elective surgical reconstruction of the abdominal aorta were divided into two groups. Patients in Group I (nine) were given dopamine intravenously, in a dose of 2 micrograms/kg/min, during the first half of the period of cross-clamping, whilst those in Group II received dopamine during the second half. Each patient acted as his own control and for each, three periods were examined, namely: pre-clamp, clamping with dopamine and clamping without dopamine. Dopamine infusion during aortic clamping caused a significant rise in sodium output (P less than 0.01), potassium output (P less than 0.05), creatinine clearance (P less than 0.05) and urine output (P less than 0.05). We conclude that dopamine infusion during aortic clamping helps to protect the kidney from any deleterious effect of clamping.     

Modification of human thrombin: effect on thrombomodulin binding

Thrombomodulin, an endothelial cell protein, binds thrombin with high affinity and alters thrombin from a procoagulant to an anticoagulant molecule. In this study, chemical and/or proteolytic modification of thrombin was carried out to identify the essential components required for its interaction with thrombomodulin. Modification of thrombin at the catalytic site serine and histidine residues, with Diisopropylfluorophosphate and Tosyl-L-lysine chloromethyl ketone, resulted in loss of clotting and amidolytic activity. Both Diisopropyl phosphoryl-thrombin and Tosyl-L-chloromethyl ketone-thrombin inhibited native-thrombin: thrombomodulin catalyzed protein C activation with Ki values of 5 nM and 6 nM respectively indicating no loss of affinity for thrombomodulin. Oxidation of tryptophan residues with N-bromosuccinimide or iodination of tyrosine residues of thrombin led to reduced clotting and amidolytic activity as well as a reduced ability to interact with thrombomodulin. Modification of arginine residues with Phenylglyoxal and 2,3,Butanedione led to loss of thrombomodulin binding affinity. Limited proteolysis of thrombin by trypsin yielded the derivative beta-thrombin which had also lost its ability to interact with thrombomodulin. Deglycosylation of thrombin did not alter its binding affinity for thrombomodulin. These results indicate that one or more tryptophan, arginine and tyrosine residues are essential for the recognition of thrombin by thrombomodulin whilst the carbohydrate side chain and the active site residues of the thrombin molecule are not involved in thrombomodulin binding.     

Detection of refrigerator-associated 60 Hz alternating current as ventricular fibrillation by an implantable defibrillator.

This report describes a patient with an implantable defibrillator who suffered an inappropriate defibrillation shock upon retrieving some food items from his inadequately earthed refrigerator. Noise typical of electrical interference can be observed in the stored electrogram of the episode. The patient was instructed to earth his home appliances, but he decided to avoid his refrigerator altogether, and has had no subsequent shocks.     

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC ANALYSIS OF RANITIDINE IN PLASMA AND URINE

A high-performance liquid chromatographic method for the analysis of ranitidine in plasma and urine is described. Plasma samples were extracted with dichloromethane while urine samples were injected directly after dilution. The mobile phase consisted of: 0.05 M ammonium acetate buffer containing 0.01 M octane sulphonate, 5.3%; methanol, 31.6%; and acetonitrile, 63.1%. Detection was carried out at 330 nm. Metoclopramide was used as the internal standard. Peak height ratios were measured. Absolute recovery from plasma was 83-85%. Within and between day coefficients of variation ranged from 0.79 to 2.42% and 1.09-2.95% respectively. Plasma and urine samples from a healthy volunteer were analysed.