A Phase I study of combined modality (90)Yttrium-CC49 intraperitoneal radioimmunotherapy for ovarian cancer.

PURPOSE: The purpose of this study was to determine the feasibility and maximum tolerated dose of (90)Yttrium-CC49 ((90)Y-CC49) as the radioimmunotherapy (RIT) component of an i.p. combined modality treatment for recurrent ovarian cancer. EXPERIMENTAL DESIGN: A Phase I trial of (90)Y-CC49 RIT was conducted in ovarian cancer patients who had persistent or recurrent intra-abdominal disease, had failed one or two prior chemotherapy regimens, and demonstrated TAG-72 expression. Patients were treated with a previously established combined modality treatment protocol of s.c. IFN alpha2b, i.p. paclitaxel, and increasing dosages of i.p. (90)Y-CC49. Patients were monitored for toxicity, generation of human antimouse antibody response, and clinical efficacy. RESULTS: Twenty eligible patients were treated per study specifications. All patients had been treated with debulking and paclitaxel/carboplatin-based chemotherapy at initial diagnosis. The patients included 11 patients with persistent disease at the time of second look laparotomy and 9 patients with delayed recurrence. Patients were treated with i.p. (90)Y-CC49 given in combination with s.c. IFN alpha2b (dose of 3 x 10(6) units for a total of four doses) and i.p. paclitaxel (dose of 100 mg/m(2)). RIT treatment was associated with primarily hematological toxicity. The maximum tolerated dose of i.p. (90)Y-CC49 was established at 24.2 mCi/m(2) in this combined regimen. Of nine patients with measurable disease, two had partial responses lasting 2 and 4 months. Of 11 patients with nonmeasurable disease, median time to progression was 6 months in 7 patients who recurred; 4 of these patients remain no evidence of disease at 9+, 18+, 19+, and 23+ months. CONCLUSIONS: (90)Yttrium-CC49-based RIT in combination with IFN alpha2b and i.p. paclitaxel is feasible and well tolerated at a dose of < or =24.2 mCi/m(2).     

Opioids confer myocardial tolerance to ischemia: interaction of delta opioid agonists and antagonists

BACKGROUND: Mammalian hibernation biology is now known to be mediated by delta opioids. The altered myocellular physiology of hibernation closely parallels that of hypothermic ischemia used to protect the heart for cardiac surgery. METHODS AND RESULTS: The present study examined the interaction of delta opioid agonists and antagonists on myocardial tolerance to ischemia. By means of a nonhibernating isolated rabbit heart model, functional and metabolic myocardial parameters were assessed during nonischemic baseline and postischemic recovery periods. Control hearts with standard cardioplegic protection alone were compared with those with cardioplegia plus preperfusion with a delta opioid agonist, a delta opioid antagonist, or both. All hearts were then subjected to 2 hours of global ischemia. Compared with cardioplegia alone, postischemic left ventricular developed pressure, coronary flows, and myocardial oxygen consumption were all increased with administration of delta opioid agonists and decreased below baseline with delta opioid antagonists. Functional recovery of left ventricular developed pressure was improved with opioids (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist: 65 +/- 5 mm Hg, P <.01) and inhibited with antagonists (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid antagonist: 17 +/- 5 mm Hg, P <.05), and true to form, the protective opioid effect was negated when combined with an antagonist (control hearts: 36 +/- 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist and delta opioid antagonist: 42 +/- 4 mm Hg, P = not significant). CONCLUSIONS: This study demonstrates that cardiac tolerance to ischemia may be mediated by delta opioids.     

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group Study

From October 1995 to March 1997, a phase II trial of topotecan was carried out in chemotherapy-naive women with advanced, persistent, or recurrent uterine leiomyosarcomas. Thirty-six patients were entered. Median age was 53 years. Performance status was 0 (50%) in 18, 1 (36%) in 13, and 2 (14%) in 5. Most patients, 33 (92%), had undergone prior surgery, and 8 (22%) prior radiation therapy. Topotecan, 1.5 mg/m2. was administered intravenously daily for 5 days, every 3 weeks, until progression of disease or adverse affects prohibited further therapy. Patients received 1 to 13 courses with a median of 3 courses. The most frequent grade 4 adverse effects were neutropenia in 28 (78%), leukopenia in 8 (22%), thrombocytopenia in 3 (8%), and anemia in 3 (8%). Complete response was seen in 1 (3%), partial response in 3 (8%), stable disease in 12 (33%), and increasing tumor in 20 (56%). Thus topotecan at this dose and schedule does not appear to have major activity in uterine leiomyosarcomas.     

Physiological response to organophosphate residues in field workers

The physiologic response of 21 male agricultural field workers exposed to foliage-borne Guthion residues was monitored during routine peach-thinning operations in a northern California orchard. Surveillance included daily venipuncture and urine collection to determine whole blood cholinesterase (CHE) activity and level of dialkylphosphate excretion for 3 baseline (nonexposed) and 5 normal work days. Foliage samples were obtained to measure dislodgeable and total Guthion residues. A decrease in group-mean CHE activity by 15% over the surveillance period was found. Apart from one worker who showed a consistent decrease in CHE activity, reaching a maximum of 30% below baseline at the end of the work week, daily changes in individual CHE activity were erratic. Group-mean dialkylphosphate excretion levels provided a semiquantitative indication of exposure to Guthion. Medical examination before and after the exposure period revealed an absence of clinical signs of organophosphate intoxication.