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Biomedical subjects

R B Edwards

Publications and source records attributed to R B Edwards.

At least 55 records · Page 3Linked to original sources

Association of changes in intracellular cyclic AMP with changes in phagocytosis in cultured rat pigment epithelium.

Papavarine, cholera toxin, and isoproterenol each elevated cyclic AMP in cultured rat retinal pigment epithelium and reduced the phagocytosis of isolated rod outer segments (38-66% of controls) during a 4 hour incubation. In addition, cultured pigment epithelium was preincubated with 25 mM exogenous cyclic AMP for two days and then incubated with outer segments for 4 hours either in the continued presence of exogenous cyclic AMP (condition A) or in the absence of exogenous cyclic AMP (condition B). Under condition B phagocytosis was 38% higher than under condition A. Intracellular cyclic AMP decreased under condition B but remained constant under condition A. These observations provide evidence that short term decreases in intracellular cyclic AMP are associated with increases in phagocytosis of outer segments by cultured rat pigment epithelium.

Animals↗

Pain and the ethics of pain management.

In this article I clarify the concepts of 'pain', 'suffering', 'pains of body', 'pains of soul'. I explore the relevance of an ethic to the clinical setting which gives patients a strong prima facie right to freedom from unnecessary and unwanted pain and which places upon medical professionals two concomitant moral obligations to patients. First, there is the duty not to inflict pain and suffering beyond what is necessary for effective diagnosis, treatment and research. Next, there is the duty to do all that can be done to relieve all the pain and suffering which can be alleviated. I develop in some detail that individuality of pain sensitivity must be taken into account in fulfilling these obligations. I explore the issue of the relevance of informed consent and the right to refuse treatment to the matter of pain relief. And I raise the question of what conditions, if any, should override the right to refuse treatment where pain relief is of paramount concern.

Attitude of Health Personnel↗

A tableted enzymic reagent for salicylate, for use in a discrete multiwavelength analytical system (Paramax).

A fully enzymic reagent for determination of salicylate in serum has been developed for use in the Paramax analytical system. The assay, run as an equilibrium determination, is based on the reaction of salicylate with NADPH and oxygen in the presence of salicylate hydroxylase (EC 1.14.13.1) to form catechol, NADP+, carbon dioxide, and water. The reaction is complete within 7 min, after which time the resulting absorbance change at 340/405 nm is measured. The sample:reagent ratio is 1:60 (5 microL of sample in a 300 microL final reaction volume). A single 30-mg tablet contains all of the reactants with tableting excipients. The use of NADPH eliminates interferences from reactions involving NADH. The large sample:reagent ratio, high sensitivity, and choice of bichromatic wavelengths minimize sample error. Results are linearly related to salicylate concentration to 1500 mg/L. Precision (CV) is 1.7% at 540 mg/L and 2.4% at 280 mg/L.

Autoanalysis↗

Discrete automated chemistry system with tableted reagents.

An instrument/reagent system with tableted reagents has been developed for performing ultraviolet/visible photometric assays. Preformed disposable plastic cuvettes pass through a stationary track every 5 s, providing a maximum throughput of 698 tests/h. The photometric system consists of a single light source with a separate set of light guides for each of eight photometer stations; bichromatic readings are possible at any of seven wavelengths between 340 and 630 nm. Tablets for 30 different analytes have been developed, each of which contains all necessary components for a single determination. Tablets are dispensed from disposable dispensers into cuvettes under the direction of the system's microprocessor and are completely dissolved within 45 s by ultrasonic agitation. Sample volumes range from 2 to 20 microL. Test requests are selected on a cathode-ray tube display, and sample-container bar-code labels are automatically printed. Sample entry is totally random. The system is designed to provide reagent quality control and also serum and reagent blank corrections for each test. Examples of equilibrium, zero-order, and first-order kinetic assays are presented.

Alkaline Phosphatase↗

Glycosaminoglycan synthesis by cultured human retinal pigmented epithelium from normal postmortem donors and a postmortem donor with retinitis pigmentosa.

Cultured human retinal pigmented epithelium (RPE) synthesized and secreted glycosaminoglycans (GAGs) with the characteristics of chondroitin sulfate, dermatan sulfate, and hyaluronic acid from radioactive precursors. Cells subcultured for up to 18 passages from normal RPE and from the RPE of a patient with X-linked retinitis pigmentosa synthesized and secreted the same types and proportions of GAGs as primary cultures of normal RPE. Extracts of native human interphotoreceptor matrix contained hyaluronic acid and chondroitin sulfate but little or no dermatan sulfate, and the chondroitin sulfate differed in electrophoretic mobility and enzyme susceptibility from the chondroitin sulfates secreted by cultured RPE. Cultured human choroidal cells and cultured human skin fibroblasts secreted a much higher proportion of hyaluronic acid than cultured RPE. This study demonstrates that the profile of GAGs synthesized from radioactive precursors and secreted by cultured human RPE is a specific and stable characteristic of these cells that is retained even after extensive proliferation in vitro.

Adolescent↗

Mental health as rational autonomy.

Rather than eliminate the terms "mental health and illness" because of the grave moral consequences of psychiatric labeling, conservative definitions are proposed and defended. Mental health is rational autonomy, and mental illness is the sustained loss of such. Key terms are explained, advantages are explored, and alternative concepts are criticized. The value and descriptive components of all such definitions are consciously acknowledged. Where rational autonomy is intact, mental hospitals and psychotherapists should not think of themselves as treating an illness. Instead, they are functioning as applied axiologists, moral educators, spiritual mentors, etc. They deal with what Szasz has called "personal, social, and ethical problems in living." But mental illness is real.

Brain Diseases↗

Selective phagocytosis of liposomes by cultured RCS rat pigment epithelium.

Liposomes 0.5 to 5 micron in diameter and of various phospholipid compositions were used as a simplified model of rod outer segment membranes to examine the phagocytic mechanism of cultured explants of retinal dystrophic Royal College of Surgeons (RCS) and normal Long-Evans (LE) rat pigment epithelium. RCS pigment epithelium explants phagocytized liposomes composed of phosphatidylserine (pS) plus phosphatidylinositol (pI). However, phagocytosis was not observed in RCS pigment epithelium explants incubated with liposomes composed of phosphatidylcholine (pC) plus phosphatidylserine (pS), phosphatidylethanolamine (pE) plus phosphatidylinositol (pI), or pC + pS + pI + pE. Normal LE pigment epithelium explants phagocytized all preparations of liposomes. The ability of RCS pigment epithelium to differently phagocytize liposomes preparations of different phospholipid composition supports the idea that phospholipids in the membrane may participate in the phagocytic mechanism.

Animals↗

Phagocytosis of outer segments by cultured rat pigment epithelium. Reduction by cyclic AMP and phosphodiesterase inhibitors.

Phagocytosis of isolated outer segments by cultured rat pigment epithelium was decreased by cyclic 3',5'adenosine monophosphate (cyclic AMP), dibutyryl cyclic AMP, and three phosphodiesterase inhibitors (isobutylmethylxanthine, papaverine, and SQ 65442). Cyclic GMP and its dibutyryl derivative had little effect on phagocytosis. Phagocytosis was moderately reduced by several other purine nucleotides and nucleosides and substantially reduced by adenine.

1-Methyl-3-isobutylxanthine↗

Defective phagocytosis of isolated rod outer segments by RCS rat retinal pigment epithelium in culture.

Retinal pigment epithelium cultured from normal rats phagocytizes large amounts of rod outer segment fragments isolated from normal rats and from RCS rats with inherited retinal degeneration. Cultured RCS rat pigment epithelium rarely ingests outer segment material, although the cells extend cellular processes around fragments of either type. Both normal and RCS pigment epithelium phagocytize polystyrene spheres. This demonstrates that RCS rat pigment epithelial cells contain a defect in the mechanism for phagocytizing outer segments.

Animals↗

Culture of rat retinal pigment epithelium.

A method of preparing monolayer cultures of retinal pigment epithelium from normal pigmented neonatal rats is described. Critical features include incubating the eyes in balanced salt solution and treating with trypsin before dissecting the eyes. The tissue also has been culured from RCS rats with inherited retinal degeneration. Since the pigment epithelium has been shown to be the primary site of action of the gene for retinal dystrophy in the RCS rat, the method should be usefull in studying the defect(s) associated with this mutation.

Animals↗

Accumulation of taurine by cultured retinal pigment epithelium of the rat.

Cultured rat retinal pigment epithelium actively accumulates taurine against a concentration gradient; an intracellular concentration of 12 mM is maintained at an extracellular taurine concentration of 0.12 mM. Taurine accumulation conforms to Michaelis-Menten kinetics for extracellular taurine concentrations between 0.006 and 0.05 mM; within that range the Km is 16 muM and the Vmax is 2.3 nmol./hr./mul of cells. Above an extracellular concentration of 0.5 mM the kinetics are complex. Accumulation is inhibited by reduced temperature and iodoacetate as well as by dinitrophenol in the absence of glucose. Ouabain, reduced extracellular sodium, and removal of extracellular potassium and calcium also inhibit taurine accumulation. The cells also release previously accumulated taurine at half-time of 1 to 3 hours. The rapid accumulation and release of taurine by cultured retinal pigment epithelial cells is consistent with the idea that this tissue is a site for the transport of taurine in vivo.

Animals↗

The effect of monopolar radiofrequency energy on partial-thickness defects of articular cartilage.

PURPOSE: To evaluate the effect of monopolar radiofrequency (RF) energy on partial-thickness defects of articular cartilage, comparing the outcome of partial-thickness defects treated with monopolar RF energy with that of treatment by conversion of partial-thickness defects to full-thickness defects by curettage and microfracture. TYPE OF STUDY: Randomized trial using adult female sheep. MATERIALS AND METHODS: Thirty-six sheep were used in this study. Both stifles in each animal were randomly assigned to 1 of the following 3 procedures: (1) partial-thickness defect without any treatment to serve as a sham-operated control, (2) partial-thickness defect with RF energy treatment, and (3) partial-thickness defect treated by conversion of the defect to a full-thickness defect by curettage and microfracture. Nine sheep were euthanized at 0, 2, 12, and 24 weeks after surgery (n = 6 per group). After euthanasia, cartilage samples were harvested from the defect sites, and chondrocyte viability was analyzed by confocal laser microscopy using a triple-labeling technique. Cartilage samples also were decalcified and stained with hematoxylin and eosin and safranin-O for histologic analysis. Surface properties of cartilage samples were analyzed using scanning electron microscopy. RESULTS: The analysis of chondrocyte viability showed that RF treatment caused death of almost all chondrocytes in the defect. Histologic analysis showed that RF treatment caused detrimental effects to chondrocytes and proteoglycan concentration that progressed over time, and that full-thickness defects were repaired by fibrocartilage by 24 weeks after surgery. Scanning electron microscopy analysis indicated that RF-treated groups were significantly smoother and less irregular than control groups at 2, 12, and 24 weeks after surgery. CONCLUSIONS: This study showed that monopolar RF energy caused long-term damage to cartilage in this sheep model and did not appear to have the beneficial effects reported in a previous study that evaluated application of this technique using a bipolar RF probe.

Animals↗

Arthrodesis of the equine proximal interphalangeal joint: a biomechanical comparison of three 4.5-mm and two 5.5-mm cortical screws.

OBJECTIVE: To compare the biomechanical characteristics and mode of failure of 2 parallel-screw techniques for proximal interphalangeal joint arthrodesis in horses. STUDY DESIGN: Randomized block design, blocking for horse (1-5), method of screw fixation (three 4.5-mm vs two 5.5-mm), side (left limb vs right limb), and end (front limb vs hind limb). Constructs were loaded to failure in 3-point bending in a dorsal-to-palmar (plantar) direction. SAMPLE POPULATION: Twenty limbs (10 limb pairs) from 5 equine cadavers. METHODS: A combined aiming device was used to facilitate consistent screw placement. Three parallel 4.5-mm cortical screws were placed in lag fashion in 1 limb of a pair, and 2 parallel 5.5-mm cortical screws were placed in lag fashion in the contralateral limb. Arthrodesis constructs were tested in 3-point bending in a dorsal-to-palmar (plantar) direction using a materials-testing machine. Loading rate was 19 mm/s. Maximal bending moment at failure and composite stiffness were obtained from bending moment-angular deformation curves. Data were analyzed using ANOVA and chi(2) analysis. RESULTS: There were no significant differences in bending moment (P >.05, power = 0.8 @ delta = 19%) or composite stiffness (P >.05, power = 0.8 @ delta = 19%) between the 2 fixation techniques. Higher maximal bending moment was found in front limbs than hind limbs, and front limbs with two 5.5-mm screws than hind limbs with two 5.5-mm screws. In all cases, constructs completely failed. A greater number of 4.5-mm cortical screws failed than 5.5-mm cortical screws. CONCLUSIONS-In pastern arthrodesis constructs loaded in 3-point bending, end (front limb vs hind limb) affected maximal bending moment at failure of constructs. There was no significant effect of horse, treatment, or side on maximal bending moment or stiffness. Two 5.5-mm cortical screws should provide a surgically simpler pastern arthrodesis than three 4.5-mm cortical screws while maintaining similar biomechanical characteristics. CLINICAL RELEVANCE: Three 4.5-mm screws or two 5.5-mm screws will provide similar biomechanical characteristics in bending when performing equine pastern arthrodesis.

Animals↗