We report a process for oxidizing bilirubin. Hemoglobin in the presence of an oxidizing agent can effectively oxidize bilirubin. Hemoglobin can be used either in free form or immobilized. Immobilisation includes microencapsulation, covalent linkage to carriers, intermolecular crosslinking into polyhemoglobin and others. The oxidizing agent can be added in the form of a peroxide. However, no external peroxide is required when hemoglobin is co-immobilized with glucose oxidase. In this case, the oxidation reaction takes place in the presence of glucose which is normally available in the blood stream and the presence of other oxidizing agents becomes unnecessary. In cases where bilirubin is conjugated to large proteins such as albumin, oxidation can be accomplished by using hemoglobin either in free form, adsorbed or bound on a suitable surface. Polyhemoglobin or cross-linked hemoglobins can also be used as oxidation catalysts in this case.

Destructive uniaxial load tests were performed on bovine pericardium that had been chemically modified by glutaraldehyde fixation. To investigate the tearing strength of this tissue, an artificial tear, in the form of a 2mm notch, was introduced into the test specimens. Specimens without a notch, harvested from the same sites in the pericardial sac but from different sacs, were used as controls. A video system with zoom and lens magnification facilities combined with low power oblique illumination was used to observe the events leading to tissue failure. Analysis of variance demonstrated that there was no overall significant difference in tensile strength or percentage strain at fracture between the test specimens with a tear and the control specimens without a tear. Rupture of the tissue occurred following laminate debonding by shear and fibre slippage through the viscous ground matrix.

Quantitative measurement of tissue blood flow is of importance for many reasons: detection of capillary flow disturbances, evaluating indications for amputation, investigating vasospastic conditions, and evaluating vasoactive drugs or the effect of sympathectomy. Methods of investigating tissue blood flows include skin thermometry, thermal conductance or clearance, transcutaneous PO2, laser doppler flux, and photoplethysmographic techniques. A major reason that ultrasound has not previously been applied to this problem is that at the very low blood velocities in the capillaries (0.1 to 1 mm/sec) the Doppler shift is small (on the order of 1 Hz/MHz of carrier signal). Advantages of ultrasound are a noninvasive procedure and penetration depths greater than that possible with optical techniques. This paper discusses the development of a Doppler ultrasound instrument which allows spectral resolution of the velocities in tissue blood flow. Briefly, a low phase noise oscillator at 7.5 Mhz is used with two transducers to obtain the shifted signal. After mixing with the fundamental, the resulting low frequency signal is fed into a high resolution spectrum analyzer for analysis.

In order to study developmental aspects of colonic motility, we have developed a miniaturized electrophysiologic recording system for use in the infant primate rhesus (Macaca mulatta). Technical considerations including absence of rectal valves, decreased tissue thickness and small colonic diameter limit application of standard non-surgical recording methodology in this model. In-vivo testing with 4 different bipolar electrode probe configurations yielded satisfactory quality recordings only with silver chloride suction electrodes. Using this system, colonic slow waves and spike action potentials were studied in 6 infant primates (ages 1 to 7 months) both fasting and following a standard liquid meal of 10 cc/kg. In response to feeding, colonic spike potentials increased from 7.8 +/- 1.7 to 14.2 +/- 4.1 within 15 minutes (mean spikes +/- SEM/5 min interval). The observed response of the distal colon to a meal in this model is similar to the response reported in adult humans using intraluminal recording techniques. Utilizing the described methodology, the infant primate appears to be a suitable model for investigation of developmental aspects of gastrointestinal motility and electrophysiology. These techniques have important direct applications for investigation in the human infant.

Conformable and conventional indwelling urinary catheters, made of latex coated with Teflon and of the same nominal size, were encrusted in vitro. The extent of encrustation was quantified by dissolving the deposits, determining the concentrations of calcium and magnesium in the resulting solutions (by atomic adsorption spectroscopy), and calculating the surface densities of calcium and magnesium. Surface densities of both elements were significantly less on the conformable than on the conventional catheters. This result can be explained by the pulsed flow of urine through the conformable catheter tending to dislodge deposits adhering to its inner surface. A similar action is expected to occur in vivo.

Site binding constants, calculated for the adsorption of bilirubin onto various lysine, arginine, or histidine containing oligopeptide-resins assuming either a one or two site binding model, are of the order of 10(4) M-1. Using these data it can be shown that there are positive cooperative effects for lysine-containing pendants, while arginine-containing pendants eventually result in negative cooperative behaviour. This difference in behaviour has been attributed to the difference in the side groups in the arginine and lysine pendants and is discussed in terms of the basicity of the amino acids, accessibility to the sites as a consequence of the flexibility or rigidity of the side group, and in terms of pi-pi electron interactions, where applicable.

Scientists, businessmen, universities and industries with fundamental or peripheral interests in technology as applied to life processes will be keenly interested in recent U.S. Patent Office decisions. These decisions indicate that new higher life forms, animal or plant, are proper subjects of patents if they are not naturally occurring (and are not human in the case of animals). In contrast to plants and other organisms, genetically modified animals have had no mode of protection as intellectual property except possibly as a trade secret or utility patent. The Ex parte Allen decision, reached by the Patent Office Board of Appeals and Interferences, directly addressed the issue of animal patentability in view of the broad reading of 35 U.S.C. section 101 by the U.S. Supreme Court in the Chakrabarty decision. The subject invention concerned polyploid oysters. Claims directed toward polyploid oysters produced by a particular process were rejected under 35 U.S.C. section 103 and section 101. The Board, reversing the 35 U.S.C. section 101 - based rejection in view of the Chakrabarty decision, indicated that the claimed polyploid oysters were non-naturally occurring manufactures or compositions of matter within the confines of patentable subject matter under 35 U.S.C. section 101. A similar decision affecting the patentable status of plants or segments thereof had previously been reached by the Patent and Trademark Office in the case of Ex parte Hibberd, 227 U.S.P.Q. 443 (Bd. Pat. App. 1985). The Hibberd utility patent application concerned "genetically engineered" maize which had high levels of the tryptophan.

Substitution solutions used for plasmapheresis (PH) may be human albumin, serum protein conserves or plasma. 746 plasmapheresis carried out on 88 patients with a variety of diseases were examined and the side effects due to the substitution solutions were investigated. Side effects occurred in less than 10% of the cases where the four substitution solutions were used. The least side effects were observed in treatments using human albumin as substitution. Side effects increased for serum protein conserves, followed lyophilised plasma and were highest for fresh frozen plasma. In view of these possible side effects the criteria for PH should be strictly observed and the substitution solution should meet clinical requirements.

Peritoneal oxygenation is a proposed method of augmenting a patient's oxygen supply via a non-pulmonary pathway. Thirteen experiments were performed in which an oxygenation fluid was infused into the peritoneal cavity of a dog and allowed to remain for 18 minutes to almost one hour. The two oxygen transporting fluids tested were: 1) a slightly hypertonic aqueous solution of NaCl and dextrose, and 2) perfluorodecalin. A one-compartment open model was developed to describe the decrease of the PO2 in the infusion solution with time. A second mathematical model was developed to determine the limitation blood flow placed on oxygen transport. Even though no physiologic signs of oxygen uptake were observed in dogs with normal lung function, physiologically significant oxygen delivery was evidenced in acutely hypoxic animals.

Antipyrine metabolism was determined in conscious, unrestrained rats after isovolemic hemodilution with FluosolR-DA. Rats received an intravenous antipyrine dose (20 mg/kg) 0.5, 24, 48, or 72 hours after hemodilution and the pharmacokinetic parameters were compared to non-exchanged control (CONT) animals. Antipyrine clearance (Cl) was significantly decreased at 0.5 and 72 hours after hemodilution. Hemodilution did not significantly alter the antipyrine apparent volume of distribution (Vd) for 48 hours; however, Vd was significantly decreased by 60% at 72 hours. The cytochrome P-450 mediated formation of 3OHME and 4OH was significantly increased at 48 and 72 hours due to an increased metabolite formation rate constant (kf) and not an enhanced metabolic clearance (Clm).