Physico-chemical and toxico-hygienic aspects of using ethylene oxide for the sterilization of articles for medical use. Part 2. Toxicity and risk of ethylene oxide entering the organism by non-inhalation routes

Results of investigation of toxicity of ethylene oxide (EO) entering the organism by routes other than inhalation (subcutaneous, intramuscular, intraperitoneal, intravenous) have demonstrated that the substance causes intoxication characterized by polytropic effect on many vitally important organs and systems. The changes in most of the indices under study show a phasic character and dose-time dependence. In both the acute and chronic effect, impairment of the state of the nervous system, the liver, kidney, blood and reactivity of the organism come to the foreground. After one single entrance, EO becomes manifest as a low-risk (class 4) compound (Limac for subcutaneous, intraperitoneal and intravenous routes being 5.0, 0.5 and 1.0 mg/kg, respectively); after repeated exposure as a high-risk (class 2) compound (Limchr for subcutaneous and intraperitoneal route being 1.0 and 0.1 mg/kg, respectively). In comparison with the subcutaneous route, the intravenous and intraperitoneal routes are more dangerous. The obtained parameters of EO toxicometry can be used as a basis for the calculation of safe levels of residual quantities of the compound in articles for medical use.     

Physicochemical, toxicological and hygienic aspects of ethylene oxide application for the sterilization of medical products. III. Setting hygienic norms in sterilized medical products

Some of the drawbacks are discussed associated with hygienic norms for gaseous sterilizing agents in polymeric products for medical applications. A new approach is proposed for regulating ethylene oxide (EO) in such products. To this end, limiting types of biological effect and its pathways have been determined and substantiated as well as the reliability factor for establishing hygienic norms for EO in medical products. Daily threshold EO limit values were calculated for momentary and repeated exposure of humans. The duration of long-term and short-term exposure of the patient to sterilized products was evaluated on the basis of EO extraction kinetics from a variety of materials. Using daily threshold limit values, threshold residual values (TRV) of EO were calculated for different groups of polymeric products for medical applications.     

Studies on the sterilization of pharmaceutical base materials with ionizing radiation and ethylene oxide.

The use of ionizing radiation and ethylene oxide for the sterilization of pharmaceutical base materials of animal origin, used to produce organopreparations, was studied. The materials included liver extract, pancreas extract, dried thyroid and intrinsic factor. The effective sterilizing doses for the examined materials and dependence between effective ionizing radiation dose and primary contamination were determined.     

Aeration time following ethylene oxide sterilization for reusable rigid sterilization containers: concentration of gaseous ethylene oxide in containers

Because ethylene oxide (EO) gas is toxic to humans, restrictions have been imposed on its use for sterilization, specifying allowable levels of residual EO remaining in sterilized apparatus and materials. However, the aeration time that optimizes the removal of the remaining EO when a rigid sterilizing container is used for a vessel had not been identified. Therefore, polyvinyl chloride, which easily adsorbs EO, was placed in rigid sterilizing containers, and aeration was carried out after 1, 8, 12, 17, and 24 hours. After standard EO sterilization, the EO concentrations remaining in the air in the rigid containers were measured. The results indicate that a period of 17 hours of aeration is appropriate when a rigid sterilizing container is used.     

Comparison of European and US biological indicators for ethylene oxide sterilization

Summary Biological indicators (BIs) are used to monitor ethylene oxide (EO) gas sterilization processes for medical devices. Several European and United States BIs for EO sterilization were evaluated for resistance according to both United States Pharmacopeia (USP) XXI and United Kingdom's (UK) tests for D-values. US BIs areB. subtilis var. niger spores on paper strips or disc carriers while European BIs use aluminum strips, quartz sand, or cotton yarn. Numerous BIs per run and runs per lot, as well as 2–3 different lots of BIs from each manufacturer, were examined. Both British and US BIs met their respective label claims for rates of inactivation when tested against British and USP EO test parameters, respectively. However, Danish BIs, on cotton yarn or quartz sand, were not inactivated following USP specifications during the exposure dwell times tested (600 mg L^–1 EO, 54°C, 60% RH, 0–110 min). The Danish BIs will require further testing in order for us to determine if theirB. subtilis spores are unusually resistant to EO or if the spore carrier substrates protect the spores from the sterilizing gas. In conclusion, the British and American BIs for EO sterilization are equivalent in resistance despite differences in carrier substrate, recovery conditions, calculation methods for D-values, and the labeled sterilization conditions for use.     

Effects of temperature and relative humidity on biological indicators used for ethylene oxide sterilization.

A study was made to determine the effects of temperature and moisture on the D-value of a common biological indicator. Relative humidity (RH) was varied between 10 and 70% in increments of 10%, and temperature was varied between 30 and 70 degrees C in increments of 10 degrees C. Temperature was found to have a pronounced effect on the D-value. At 60% RH, the D-value varied from 15.0 min at 30 degrees C to 1.1 min at 70 degrees C. When RH was plotted against the average D-value at the various temperatures, the temperature curves at or above 50 degrees C were more erratic and the RH had a significant effect. The study showed that temperature and RH must be controlled if biological indicators are to be properly calibrated for use in ethylene oxide sterilization.     

The use of information technology in improving medical performance. Part I. Information systems for medical transactions

Investment in medical information technologies reached $15 billion in 1996. However, these technologies have not had the wide impact predicted in streamlining bureaucracy, improving communications, and raising the effectiveness of care. In this series, we identify how such technologies are being used to improve quality and performance, the future directions for advancement, and the policy and research developments required to maximize public benefit from these technologies. Each of these articles focuses on a different type of information technology: (1) information systems to manage medical transactions; (2) physician-support technologies to improve medical practice; and (3) patient-focused technologies designed to change how people manage their own care. This first article of a 3-part series examines the successes of and opportunities for using advanced information systems that track and manage medical transactions for large populations to improve performance. Examples of such systems include: HEDIS, which gathers standardized data from health plans on quality of care; the USQA Health Services Research Program, which tracks treatment patterns and outcomes for 14 million insurance members; Ford's program to collect medical data for over 600,000 employees; and Harvard Pilgrim Health Care's system of computerized laboratory, pharmacy, ambulatory, and hospital admission records for its 1.5 million members. Data from these systems have led to modest improvements in knowledge and practice patterns for some diseases. Significant barriers are slowing efforts to add outcomes data to these databases and broaden the databases to cover larger populations. Nonetheless, existing data in currently evolving systems could be used to greater benefit in tracking public health and in identifying more effective treatments and causes of diseases.     

Cannabidiol: an overview of some chemical and pharmacological aspects. Part I: chemical aspects

Over the last few years considerable attention has focused on cannabidiol (CBD), a major non-psychotropic constituent of Cannabis. In Part I of this review we present a condensed survey of the chemistry of CBD; in Part II, to be published later, we shall discuss the anti-convulsive, anti-anxiety, anti-psychotic, anti-nausea and anti-rheumatoid arthritic properties of CBD. CBD does not bind to the known cannabinoid receptors and its mechanism of action is yet unknown. In Part II we shall also present evidence that it is conceivable that, in part at least, its effects are due to its recently discovered inhibition of anandamide uptake and hydrolysis and to its anti-oxidative effect.     

Examining axial diffusion of nitric oxide in the lungs using heliox and breath hold.

Exhaled nitric oxide (NO) is highly dependent on exhalation flow; thus exchange dynamics of NO have been described by multicompartment models and a series of flow-independent parameters that describe airway and alveolar exchange. Because the flow-independent NO airway parameters characterize features of the airway tissue (e.g., wall concentration), they should also be independent of the physical properties of the insufflating gas. We measured the total mass of NO exhaled (A(I,II)) from the airways after five different breath-hold times (5-30 s) in healthy adults (21-38 yr, n = 9) using air and heliox as the insufflating gas, and then modeled A(I,II) as a function of breath-hold time to determine airway NO exchange parameters. Increasing breath-hold time results in an increase in A(I,II) for both air and heliox, but A(I,II) is reduced by a mean (SD) of 31% (SD 6) (P < 0.04) in the presence of heliox, independent of breath-hold time. However, mean (SD) values (air, heliox) for the airway wall diffusing capacity [3.70 (SD 4.18), 3.56 pl.s(-1).ppb(-1) (SD 3.20)], the airway wall concentration [1,439 (SD 487), 1,503 ppb (SD 644>)], and the maximum airway wall flux [4,156 (SD 2,502), 4,412 pl/s (SD 2,906)] using a single-path trumpet-shaped airway model that considers axial diffusion were independent of the insufflating gas (P > 0.55). We conclude that a single-path trumpet model that considers axial diffusion captures the essential features of airway wall NO exchange and confirm earlier reports that the airway wall concentration in healthy adults exceeds 1 ppm and thus approaches physiological concentrations capable of modulating smooth muscle tone.     

Staining kinetics in single cells. Part I. Influence of convective diffusion on the staining rate

The staining kinetics of single cells have been investigated using a perfusion cuvette in combination with a computer controlled microscope spectrometer. The physicochemical hydrodynamics of staining are characterized. Using a steady-state laminar flow parallel to the cell surface a hydrodynamic and a diffusional boundary layer are observed which are determined by the flow rate. The thickness of the diffusional boundary layer revealed by experimental data is in agreement with theoretically calculated values. At certain well-defined hydrodynamic conditions convective diffusion has no further effect on the staining rate.     

Biodegradable polymeric nanospheres formed by temperature-induced phase transition in a mixture of poly(lactide-co-glycolide) and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer

The mixture of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer(F-127) and PLGA (poly(lactide-co-gycolide)) forms a liquid state above their phase transition temperatures, and the phase-separated state is induced by decreasing the temperature below the phase transition temperature. On the basis of the temperature-induced phase transition behavior in the mixture of F-127 and PLGA, a novel method for the preparation of drug-loaded PLGA nanospheres was designed and characterized by measuring the loading amount, the encapsulation efficiency, and the drug release pattern. Paclitaxel, used as a potent anticancer drug, was selected as a model drug.     

Some mathematical aspects of the medical diagnostic process. I: a general mathematical model

Making a medical diagnosis consists of correlating knownpatterns of disease with the various classes of clinical data elicited from the history, physical examination, and batteries of tests relative to the diagnostic dynamics symbolized by atree branching into the various possible diagnostic decisions. In this paper a relational mathematical model of the reasoning aspects of the conventional medical diagnostic process is suggested as a way of extracting a general, formal concept of medical diagnosis. Computer implementation of the model is discussed briefly.