Surface contamination with antineoplastic agents in six cancer treatment centers in Canada and the United States.

The level of contamination by antineoplastic agents in drug preparation and administration areas in cancer treatment centers in Canada and the United States was determined. Sampling locations at three cancer treatment centers in Canada and three centers in the United States were selected (biological safety cabinets, countertops, and floors in and adjacent to preparation areas; tabletops, chairs, and floors in administration areas). A solution of sodium hydroxide (0.03 M) was spread over the surface of each area. The surface was wiped with one or two absorbent tissues, which were then stored in plastic screw-top containers. Samples were stored at -40 degrees C before analysis of ifosfamide content (U.S. centers only) and cyclophosphamide content by gas chromatography in tandem with mass spectroscopy-mass spectroscopy and fluorouracil content by reverse-phase high-performance liquid chromatography with ultraviolet-light detection. Measurable amounts of the antineoplastic agents were detected in 75% of the pharmacy samples and 65% of the administration samples. In general, the levels of contamination were higher in the pharmacy areas than in the drug administration areas. The pharmacy area at the site with the highest number of drug preparations had considerably more drug contamination than the other sites. The results were similar for Canadian and U.S. centers. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.

Endometrial transport generates the maternal-fetal electrical potential difference in guinea pigs.

These studies examined the transport characteristics of the uterine endometrium with respect to the origin and mechanism of generation of the maternal-fetal electrical potential difference (PD) in pregnant guinea pigs. Late-gestation animals were used in two experimental preparations. In vivo, a sealed uterine pouch that preserved blood flow to the endometrium was prepared by removal of the fetus, placenta, and fetal membranes from the uterus and replacement with Earle's solution, a balanced electrolyte solution. In vitro, sections of uterine wall comprised of myometrium and endometrium without fetal membranes were mounted in Ussing chambers. Transuterine PDs (fetal side negative) were indistinguishable in vivo and in vitro, averaging 29.6 +/- 4.5 and 32.6 +/- 6.1 (95% confidence interval) mV in the respective preparations. Both values are within the range of maternal-fetal PD measured in intact guinea pigs, indicating that the fetoplacental unit is not essential in generating an intrauterine PD. The maternal-fetal PD, therefore, is likely a passive result of the fetus and placenta being immersed in fluids at the intrauterine potential. In vitro, both PD and short-circuit current (Isc) were completely inhibited by ouabain (10(-3) M) at the serosal (maternal) side of the uterine wall but unaffected by the inhibitor from the luminal (fetal) side. Amiloride (10(-5) M) and valinomycin (10(-5) M) caused decreases in the PD when added to the luminal side, both in vivo and in vitro, and were both ineffective from the serosal side in vitro. Isc was reduced 83% from 315 +/- 24 to 53 +/- 6 (SE) microA/cm2 after luminal amiloride (5 x 10(-4) M), indicating that Na+ is the predominant ion actively transported.(ABSTRACT TRUNCATED AT 250 WORDS)

Update on safe handling of hazardous drugs: the advice of experts.

Questions related to the handling of hazardous drug products were discussed by a panel of pharmacy practitioners. The panel addressed the following issues: pharmacists' responsibilities for instructing patients, nurses, and physicians on safe handling of hazardous drug products; safe transport of hazardous drug products outside the hospital; disposal of hazardous drug products, items contaminated by these products, and body wastes of patients receiving these drugs; appropriate operation, venting, cleaning, decontamination, and recertification of biological safety cabinets (BSCs); the protective clothing and technique that should be used by workers in BSCs; monitoring the health of workers who handle hazardous drug products; pharmacy's potential liability for nonconformance to published guidelines; whether and how pharmacies that prepare few doses of hazardous drug products should comply with stringent guidelines geared to institutions that handle many doses of these products; and precautions for handling hazardous drug products for oral administration, caustic products, and vesicants. Safe limits for time and amount of exposure to hazardous drugs are unknown, but ASHP's revised Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs and current guidelines from the federal Occupational Health and Safety Administration provide guidance on precautions that should be observed.

Transuterine ion movement and electrical potential difference in pregnant guinea pigs.

An investigation of the site and mechanism responsible for the maternal-fetal electrical potential difference (PD) was done in 11 anesthetized guinea pigs at 54-56 days gestation. We removed the most distal fetus and placenta from one uterine horn and secured a catheter, thermistor, and Ag-AgCl electrode in the resulting pouch. The pouch was filled with Earle's solution. We placed another thermistor and electrode in the maternal abdomen. The PD between electrodes was monitored continuously; periodic samples of maternal blood and intrauterine fluid were taken. Thirty minutes after the uterus was filled, the PD (uterine cavity negative) averaged 29.6 +/- 4.5 (95% confidence interval of the mean) mV. Over 4 h, intrauterine K+ concentration [( K+]) decreased from 4.9 to 2.6 +/- 0.5 meq/l, against a chemical and electrical gradient. In eight animals, we measured bidirectional Na+ flux using 22Na and 24Na. The flux ratio was not distinguishable from unity despite a significant PD. Our data indicate that the maternal-fetal PD is probably generated by the endometrial epithelium and that Na+ and K+ both move across the epithelium by active transport or cotransport rather than simple diffusion.

Controls of corticotrophin-releasing factor output by hypothalamic tissue from fetal sheep in vitro.

Corticotrophin-releasing factor (CRF) is thought to be an important physiological regulator of the pituitary-adrenal axis in fetal sheep and, as such, plays a fundamental role in the initiation of parturition in this species. However, little is known of the controls of CRF secretion from the fetal hypothalamus. We looked for the presence of CRF in fetal hypothalami, and examined whether the hypothalamic CRF concentration or molecular species changed in relation to gestational age. We established an in-vitro perifusion system to examine the release of CRF from perifused hypothalami taken from fetuses at day 100 and day 140 of pregnancy, under basal conditions and in response to potassium depolarization and/or dexamethasone administration. Immunoreactive CRF was present in fetal hypothalami as early as day 100 (2.42 +/- 0.99 (S.E.M.) micrograms/g protein, n = 9) and in similar concentrations at day 140 (2.31 +/- 0.69 micrograms/g protein, n = 9). There was a significant (P less than 0.05) increase in hypothalamic CRF content to 14.79 +/- 4.09 micrograms/g protein (n = 16) between day 122 and day 135 of gestation. Using Sephadex G-75 chromatography, hypothalamic extracts at day 100, days 122-135 and day 140 eluted with a single peak of immunoreactivity which corresponded to synthetic ovine CRF(1-41). The basal release of CRF from perifused hypothalami at day 140 (76.6 +/- 10.4 pg/fraction, n = 8) was significantly (P less than 0.05) greater than at day 100 (50.1 +/- 10.2 pg/fraction, n = 11). Dexamethasone significantly inhibited basal CRF release at day 140 of gestation but not at day 100.(ABSTRACT TRUNCATED AT 250 WORDS)

Recommendations for handling cytotoxic drugs in hospitals.

Recommended procedures for handling cytotoxic drugs in hospitals are presented. The recommended procedures are designed to reduce the number of opportunities for unnecessary contact with cytotoxic agents (CYTAs) by hospital personnel and to prevent contamination of the hospital environment and staff with cytotoxic agents. The recommendations incorporate elements of previously published and unpublished guidelines; they admittedly are based on informed judgment as well. Three sets of recommended procedures are presented, each offering a varying degree of protection. The number of cytotoxic drug doses prepared and administered is suggested as the determinant of which level of protection is followed. The cytotoxic workload index, defined as the number of CYTAs prepared or administered (or both) divided by the number of available staff hours, is proposed as a quantitative method of deciding which level of protection is required for a particular work station or work shift. The recommended procedures cover the following seven topic areas: general guidelines; apparel, equipment, and facilities; drug preparation; drug administration; housekeeping, waste disposal, and management of spills and contamination; medical surveillance of staff; and legal and personnel considerations. The recommended procedures and associated equipment are considered to be practical and to adequately protect hospital personnel from risks associated with handling cytotoxic agents.