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Modification of the methacholine inhalation test and its epidemiologic use in polyurethane workers.

The dosimeter method of administering doubling cumulative doses of methacholine to measure bronchial responsiveness was standardized to control for the effects of a number of potential influencing variables. The aerodynamic mass median diameter of the challenge aerosol produced from a DeVilbiss 646 nebulizer proved to be 1.2 mu, and the mean output per inhalation 8.9 microliters. Each challenge dose comprised 5 inhalations. Cumulative doses ranged from 0.3 methacholine inhalation units (1 unit = 1 inhalation of aerosol from a 1-mg/ml solution of methacholine, i.e., 8.9 micrograms methacholine) to a possible 640 units, the maximum that was considered reasonable to avoid the risk of unacceptable systemic effects. Responsiveness was expressed as the dose provoking a 20% decline (PD20) in FEV1. Modifications in this full protocol were introduced to facilitate epidemiologic investigations. Physician assessments coupled with baseline measurements of ventilatory function allowed starting at higher dosages for persons with low probability of hyperresponsiveness, thereby shortening the time required for testing to an average of 38 min. In a validation study of 20 persons using both the full and modified protocols, no significant differences were detected between measured PD20 values (geometric means Full versus Modified, 14.83 versus 14.88; r = 0.99). The modified protocol was used to measure bronchial responsiveness in 254 workers exposed to toluene diisocyanate. It proved to be safe and acceptable. Sixty-four workers (25.2%) were found to be reactors. The frequency distribution of the PD20 values exhibited a steadily increasing trend, consistent with a unimodal distribution.

Adult↗

Seldinger technique as an alternative approach for percutaneous insertion of hydrophilic polyurethane central venous catheters in newborns.

The use of hydrophilic central venous catheters, percutaneously inserted by means of the Seldinger technique, was evaluated in this prospective study. Between 1988 and 1991, 138 catheters were inserted in newborns who were admitted to our neonatal intensive care unit. An adequate position of the tip, evaluated radiographically, was achieved in 130 (94.2%) of these insertions. The side effects associated with these 130 catheters and the duration of their use were recorded. Results were compared with those of percutaneously inserted Silastic catheters described in the literature. The rate of adequate catheter placement seems comparable. Because of a high rate of minor mechanical complications, the mean catheter duration was rather short (8.3 days). However, the incidence of serious complications, especially infectious complications, was low.

Acinetobacter Infections↗

Surface and hemocompatibility studies of bi-soft segment polyurethane membranes.

Cross-linked urethane/urea membranes with two soft segments were prepared by extending a poly(propylene oxide) based tri-isocyanate-terminated prepolymer (PUR) with polybutadiene diol (PBDO). The ratio of prepolymer and polybutadiene diol was varied to yield cross-linked membranes with different compositions, exhibiting different degrees of phase-separation of the PBDO segments in the bulk and of surface enrichment in PUR. In this work, surface energy and hemocompatibility aspects (hemolysis and thrombosis) of the PUR/PBDO membranes were evaluated. The results showed that the membrane surface energy increased with the PBDO content until 25% of PBDO, and decreased thereafter. The introduction of the second, more hydrophobic, soft segment (PBDO) in the PUR membranes turned hemolytic into non-hemolytic membranes and, for a blood-material contact time of 10 minutes, decreased the thrombogenicity significantly. The 10% PBDO membrane was the least thrombogenic and was also non-hemolytic. The hemolysis degree did not vary significantly with the PBDO content while, for blood-material contact times of 10 minutes, the thrombogenicity increased with an increase in PBDO content above 10%. Membrane thrombogenicity varied with the blood-material contact time. For blood contact times of 10 minutes, all membranes tested were less thrombogenic than glass.

Animals↗

In vivo testing of a biostable polyurethane.

At present all the commercially available "medical grade" urethane elastomers exhibit a phenomenon known as environmental stress cracking (ESC). This phenomenon is characterized by surface microcracking when the elastomer is elongated while in vivo. The degree of strain that is required to initiate microcracking varies from composition to composition. It has been found that harder compounds generally tend to have a higher strain threshold than corresponding softer ones. We theorized that this degradation occurs when certain enzymes (present only in vivo) attack and break down the ether linkages that link the polymer molecules together. Those elastomers that contain more ether linkages (such as the softer compositions) appear to microcrack more easily than elastomers with fewer ether linkages (such as the harder ones). The molecular composition of ChronoFlex urethane has been chosen so that the finished elastomer will be free of ether linkages; thus, it is expected to be immune from environmental stress cracking.

Animals↗

Effect of fabrication, sterilization and mediators--blood compatibility of polyurethanes.

The possible changes in the surface and physical properties of polyether urethane urea (PEUU) implants, including their interaction with blood, due to the different preparation methods, sterilization techniques and long term storage in different environmental conditions have been investigated by conducting the studies of mechanical properties, contact angle, platelet adhesion and protein adsorption. Considerable variations in the mechanical properties have been observed for the PEUU grafts stored in different conditions. Changes in platelet adhesion and albumin adsorption have also been observed in the case of samples that underwent different sterilization methods. The effect of mediators like bromelain, an enzyme present in pineapple juice, on albumin adsorption and platelet adhesion on PEUU surfaces have been investigated. It seems the presence of pineapple juice increases the adsorption of albumin and reduces the adhesion of platelets on PEUU surfaces.

Biocompatible Materials↗

Biodegradable polyurethanes: biodegradable low adherence films for the prevention of adhesions after surgery.

Adhesions commonly occur after internal disease or surgery. The natural healing response leads to the formation of vascular and avascular adhesions after inflammatory diseases and surgical interventions. A barrier film could be incorporated during surgery between layers of tissues that must not adhere to one another. The film would be biodegradable so that it disappears over a period of time, and would ideally be two sided, allowing relative movement at that interface, while being firmly anchored on the opposite side to prevent displacement. Polyesterurethane-polydimethylsiloxane graft polymers are synthesised. Chemical characterisation of the polymer is performed by using Fourier transform infrared spectroscopy and gel permeation chromatography. In vitro hydrolytic degradation is carried out in which films are immersed at 37 degrees C in alkaline solution. Degradation is assessed by tensile testing as a function of time to determine the degradation of mechanical strength, infrared spectroscopy, and mass loss. A titration method is also used to determine quantitatively the hydrolytic degradation. In order to study the adhesions of films, an in-vitro model based on a gelatine test, which is simple and rapid, is described. Suitable candidate films investigated from the in-vitro work are subjected to in vivo tests for both biodegradation and their ability to prevent adhesion.

Adhesiveness↗

A physiologically based pharmacokinetic model for 2,4-toluenediamine leached from polyurethane foam-covered breast implants.

Physiologically based pharmacokinetic (PBPK) modeling was used to assess the low-dose exposure of patients to the carcinogen 2, 4-toluenediamine (2,4-TDA) released from the degradation of the polyester urethane foam (PU) used in Meme silicone breast implants. The tissues are represented as five compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues (e.g., fat), and richly perfused tissues (e.g., muscle). The PBPK model was fitted to the plasma and urine concentrations of 2,4-TDA and its metabolite 4-AAT (4-N-acetyl-2-amino toluene) in rats given low doses of 2, 4-TDA intravenously and subcutaneously. The rat model was extrapolated to simulate oral and implant routes in rats. After adjusting for human physiological parameters, the model was then used to predict the bioavailability of 2,4-TDA released from a typical 4.87-g polyester urethane foam implant found in a patient who weighed 58 kg with the Meme and had the breast implant for 10 years. A quantitative risk assessment for 2,4-TDA was performed and the polyester urethane foam did present an unreasonable risk to health for the patient.

Algorithms↗