Phase II study of iproplatin in metastatic breast carcinoma

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.     

Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study.

An analysis of the Coronary Artery Surgery Registry (CASS) was performed to determine the occurrence of stroke after coronary artery bypass surgery in patients entered into the Coronary Artery Surgery Study Registry. Of the 10,098 patients having coronary artery bypass surgery at the Coronary Artery Surgery Study participating sites during the period July 1974 through May 1979, a total of 348 patients (or 3.4%) sustained a stroke during the first year after coronary bypass surgery. Fifty-nine strokes occurred on the day of surgery, and an additional 129 strokes occurred during hospitalization for coronary bypass surgery. Thus, 188 patients (1.9%) of the entire surgical group sustained a stroke during initial hospitalization for coronary artery bypass surgery. Logistic regression analysis was used to predict stroke on the day of surgery, during the hospitalization for surgery, and during the first year after surgery. The most powerful predictors of stroke on the day of coronary artery bypass surgery were: 1) older age (n = less than 0.0001); 2) use of alpha-adrenergic drugs after bypass (n = 0.0001); and 3) longer duration of cardiopulmonary bypass (n = 0.002). For those strokes occurring at least 1 day after coronary artery bypass but during the initial hospitalization, age and duration of cardiopulmonary bypass were the most powerful predictors of stroke. An analysis of predictors of stroke within 1 yr after hospital dismissal for initial coronary bypass surgery revealed that the most powerful predictor was a history of previous cerebrovascular disease (n less than 0.0001) and a history of hypertension (n less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of cigarette smoking on survival of patients with angiographically documented coronary artery disease. Report from the CASS registry

Through a multicenter registry of patients in the Coronary Artery Surgery Study, we prospectively evaluated morbidity and mortality in 4,165 smokers with angiographically proved coronary artery disease, 2,675 of whom continued to smoke and 1,490 of whom quit. At five years, mortality (adjusted by Cox analysis for baseline differences) was 22% for those who continued smoking and 15% for quitters. The relative risk (also from the Cox analysis) for mortality in continuers vs quitters was 1.55 (95% confidence interval, 1.29 to 1.85). The adverse effect of smoking mainly took the form of higher frequencies of myocardial infarction--associated death and sudden death: the frequencies of these events during follow-up in continuers vs quitters were 7.9% vs 4.4% for myocardial infarction--associated death and 2.8% vs 1.5% for sudden death. This study supports the recommendation that patients with coronary artery disease should stop smoking.     

Multicenter Pilot Study of a Serpentine Balloon-Expandable Stent (beStentTM): Acute Angiographic and Clinical Results

The beStent is a new stainless steel, balloon-expandable mesh stent which has a unique serpentine design. Rotation of the unique low stress junctions upon expansion leads to orthogonal locking of the wires, maximizing radial strength and assuring zero shortening. The stent has delineating gold markers which assure precise positioning. We aim to present the initial acute results in a pilot registry for stent evaluation. Two hundred eighty-four stents were used in a total of 217 patients (age 57.9 ± 3.10 years; 178 males; 39 females) in seven centers, for variable indications. Stents of 15-, 25-, and 35-mm length were used. The arteries treated were the left anterior descending (n = 112, 42%), circumflex (n = 54, 20.2%), right coronary (n = 95, 35.5%), left main (n = 1, 0.4%), and vein graft (n = 5, 1.9%). Lesion types were: A in 42 patients (16.5%); B1 in 53 patients (20.7%); B2 in 81 patients (31.8%); and C in 79 patients (31%). One hundred fifty-nine patients required one stent, 40 patients required two stents, and 18 patients required three or more stents. Anticoagulation protocol included procedural heparin with aspirin with/without ticlopidine. Smooth angiographie results were obtained in all cases with no plaque herniation. Acute angiographic success was obtained in 97% of the patients, and acute clinical success in 95% of the patients. Complications within 30 days were: 3 deaths (1.4%) (2 noncardiac); 2 (0.9%) myocardial infarctions; and 2 (0.9%) stent thromboses. Therefore, the beStent is useful in treatment of complex lesions of variable length and complexity, providing excellent acute results with a low complication rate, in spite of unfavorable basic clinical and angiographie characteristics.     

Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

Evidence for a non-genomic action of progestins on sexual receptivity in hamster ventral tegmental area but not hypothalamus.

Progestogenic stimulation of both the ventromedial nucleus of the hypothalamus (VMH) and the ventral tegmental area (VTA) is critical for normal receptivity in estrogen-primed hamsters. However, anatomical and biochemical studies have identified very few estrogen-induced progestin receptors in the rodent ventral midbrain. To determine whether progesterone might be working on the membrane of neurons in the VTA, progesterone 3-CMO BSA (P-3-BSA) was applied intracranially. The size of P-3-BSA makes it relatively impermeable to the cell membrane. Ovariectomized hamsters were implanted with 2 chronic cannulae, one aimed at the VMH and the other at the contralateral VTA. These animals were then estrogen-primed and tested for sexual receptivity after progesterone-containing tubes were inserted just dorsal to the VMH and P-3-BSA inserts were applied above the VTA. The following week, the hamsters were tested again with the contents of the inserts reversed. Animals with progestogenic stimulation to the VMH and P-3-BSA to the VTA were receptive yet those with P-3-BSA to the hypothalamus and progesterone to the VTA were not receptive. These data suggest that progesterone is capable of facilitating sexual receptivity within the VTA by actions on the cell membrane. The non-genomic effects in the VTA require concurrent genomic activation by progesterone within the hypothalamus.