Heart rate response of the rat fetus and neonate to a chemosensory stimulus

Resting heart rate (HR) and HR responses of fetal and neonatal rats are described before and after intraoral infusion of isotonic saline or lemon solution. Stable measurements of resting HR were obtained for fetuses over the last three days of gestation (E19, E20, E21) and pups on the day of birth (P0) and four subsequent postnatal ages (P1, P3, P5, P7). Resting HR decreased significantly on P0 relative to the three prenatal ages and exhibited a linear increase thereafter. Variability in resting HR was pronounced on E21, decreased sharply after birth, and gradually increased through P7. Developmental changes in the HR response of fetuses and pups were evident following infusion of lemon. Fetal HR responses to lemon were characterized by bradycardia, which increased in magnitude through P1, diminished after P1, and eventually changed to tachycardia by P7. Both resting HR and HR responses to chemosensory stimulation point to the immediate perinatal period as a time of quantitative and qualitative change during sensory development.     

A phase I trial of 14-day continuous intravenous infusion mitoxantrone.

Based on clinical evidence that prolonged exposure to anti-neoplastic agents may ameliorate dose-limiting toxicity while facilitating anti-tumor activity, we conducted a phase I trial of 14-day continuous intravenous infusion mitoxantrone. Study objectives were to: (1) determine the maximally tolerated dose for phase II trials; (2) determine the incidence and severity of side effects; and (3) study the pharmacokinetics of continuous infusion mitoxantrone. Sixteen patients with drug-resistant advanced cancers were entered into the trial. Three or more patients were treated at each dose level (1.0, 1.25, and 1.5 mg/m2/day) for a total of 33 courses (mean 2.1 courses/patient, range, 1-4). Courses were repeated every 4 weeks. The maximally tolerated dose (MTD) was found to be 1.5 mg/m2/day. At this dose four of six patients had grade III or IV leukopenia (mean WBC nadir 1900/microliters, range, 800-3600/microliters). Other toxicities were grade I or II stomatitis (two patients), grade I diarrhea (one patient), and grade I nausea (one patient). Renal and hepatic toxicity were not observed. No alopecia or infectious complications occurred. Pharmacokinetic studies were performed using high-performance liquid chromatography (HPLC). Steady-state plasma levels at the 1.5 mg/m2/day dose were reached by 48 h, with a mean steady-state plasma concentration of 3.2 +/- 0.7 ng/ml, mean total body clearance of 340 +/- 79 ml/min/m2, and mean area under the plasma disappearance curve (AUC) of 955 +/- 185 micrograms h/l. No responses were observed, although no patients with mitoxantrone-sensitive tumors were treated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Case report: topical DMSO for mitomycin-C-induced skin ulceration

Mitomycin-C is a commonly used anticancer drug for patients with advanced anal, breast, colorectal, gastric, lung, or pancreatic cancers. Mitomycin-C can cause severe necrosis and ulceration when extravasated inadvertently into skin and soft tissues following IV drug administration. Local applications of heat, ice, and common antidotes such as glucocorticosteroids and hyaluronidase or sodium thiosulfate have failed to reduce the experimental toxicity of these vesicant reactions in mice. Plastic surgery with split-thickness skin grafting may be required to palliate local pain symptoms and loss of function, although some extravasations heal without any local treatment. This brief communication summarizes two case reports of the treatment of severe mitomycin-C venous extravasations using topical applications of dimethylsulfoxide (DMSO). Although the authors' experience represents the results of DMSO interventions in only two patients, the response to treatment in both patients was so pronounced that others may find this useful in their practice.