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Biomedical subjects

J A Knight

Publications and source records attributed to J A Knight.

At least 37 records · Page 2Linked to original sources

Moral growth in medical students.

Although students bring to medical school a fairly well established value system, the potential for moral growth through the medical school environment and experience is substantial. The educational environment poses a succession of developmental and adaptive tasks to be accomplished. Several of these tasks are discussed her, tasks that are value-laden and involve, directly or indirectly, the interplay of ethical theory and practice. During the past quarter century, the two influences that have had the greatest impact on the moral growth and moral reasoning capacity of medical students have been the incorporation into the medical school curriculum of courses in medical humanities and the admission to medical school of an increasing number of female students. The female students have brought to medical school a level or dimension of moral reasoning (morality as care or responsibility for others) to augment the male students' focus on rights and justice considerations.

Attitude to Death↗

Intraarticular carcinogenesis bioassays of CoCrMo and TiAlV alloys in rats.

Wear-debris powders of cobalt-chromium-molybdenum (CoCrMo) and titanium-aluminum-vanadium (TiAlV) alloys, which are widely used for orthopedic implants (eg, hip and knee prostheses), were tested for carcinogenic activity following intraarticular administration (20 mg/rat) to groups of 44 male Fischer-344 rats (Charles River Breeding Laboratories, North Wilmington, MA). Control groups received similar intraarticular injections of either a noncarcinogen (manganese powder, negative control rats) or a potent carcinogen (nickel subsulfide powder, positive control rats). The experimental groups of 8-12 rats were observed for 24 months after injection. No local tumors developed at the injection site in the negative control rats or in rats that received the CoCrMo or TiAlV powders; poorly differentiated or pleomorphic sarcomas developed at the injection site in 10 of the 12 positive control rats that were treated with nickel subsulfide. Incidences of primary tumors distant from the injection site did not differ significantly among the experimental groups. This study shows that, under experimental conditions, any carcinogenic activity of CoCrMo or TiAlV wear-debris powders is weak in comparison to nickel subsulfide. Based on this study and observations in other laboratories, intraarticular administration of test materials to rats provides a practical, reliable, and biologically relevant method for carcinogenesis testing of biomaterials used for orthopedic implants.

Alloys↗

The prevalence of cervical infection with human papillomaviruses and cervical dysplasia in Alaska Native women.

Alaska Native women historically have high rates of sexually transmitted diseases (STDs) and invasive cervical cancer. Their prevalence of cervical infections with human papillomavirus (HPV) in relation to cervical dysplasia was determined with a commercial dot hybridization test for seven HPV genotypes. Type-specific HPV DNA, similarly distributed between genotype groups 16/18 and 31/33/35, was detected in 234 cervical specimens (21%) from 1126 Alaska Native women seeking routine care and colposcopy or from population-based lists. The prevalence of HPV DNA declined with age and increased with sexual activity and cigarette smoking. It was unrelated to use of oral contraceptives or condoms or to STDs. Relative risks associating HPV with increasing severe grades of cervical dysplasia increased markedly with HPV infection, up to 7.1 for high-risk genotypes 16/18 and 14.4 for coinfection with 31/33/35. These genotypes were detected in 8% of women without dysplasia seeking routine care. Screening for strain-specific HPV DNA may identify women at highest risk for cervical neoplasia.

Adolescent↗

Ethics of care in caring for the elderly.

While some ethical and value issues are unique to the care of the elderly, many are shared with other age groups in medical practice. Efforts at cost containment and the rationing of medical services are impinging deeply on the elderly and placing physicians in roles that may interfere with the covenant of faithfulness that exists between physician and patient. Physicians must examine negative societal images that may influence the care of the elderly and hold firm to the commitment to respond to the needs, values, and best interests of the elderly in the face of changing health care policies and constraints of one kind or another. Further, a major ethical imperative for physicians relates to making themselves available for the treatment of the elderly in the context of an appreciation of these patients' tasks in the final stage of development.

Aged↗

Diagnosis of superior sulcus tumors: a further use of the thoracoscope.

Most irradiation therapists require a tissue diagnosis of a superior sulcus tumor prior to initiating preoperative irradiation. In the rare case, obtaining a tissue diagnosis via the normally used procedures proves challenging. A technique for obtaining a tissue diagnosis using a thoracoscope in this circumstance is presented.

Carcinoma, Non-Small-Cell Lung↗

Lipid peroxidation in stored red cells.

Lipid peroxidation is initiated by the production of oxygen-free radicals; it is increased in a wide variety of diseases, including various hemolytic anemias, and in hemoglobin disorders. Increased lipid peroxidation occurs in red cells in the presence of reactive iron species and some heme moieties. In this study, greatly reduced concentrations of malondialdehyde, an indicator of lipid peroxidation, were observed in stored blood upon the addition of both deferoxamine mesylate and diethylenetriaminepentaacetic acid (p less than 0.001). The antioxidant glutathione was much less effective (p less than 0.01 or less than 0.05, depending on incubation time). On the other hand, the addition of dimercaptosuccinic acid and ascorbic acid both significantly increased malondialdehyde production over controls (p less than 0.001 and p less than 0.05, respectively). Ascorbic acid, in the presence of deferoxamine mesylate, added no red cell protection over that of deferoxamine mesylate alone. The addition of metal chelators and, possibly, certain antioxidants to stored blood may be effective in increasing the viability and longevity of transfused red cells.

Blood Component Transfusion↗

Acetylcholine receptors from normal human muscle: concentration, purification, and use in radioreceptor assays for autoantibodies.

We measured the concentration of acetylcholine receptor (AChR) in various normal human muscles, obtained at autopsy, in order to find a more reliable and convenient source than the amputated leg muscle from diabetic patients for the isolation of AChR. We found that human calf muscle contains the highest concentration of AChR, approaching the concentration of receptor required for the radioreceptor assay for autoantibodies in myasthenia gravis (MG). Because the amount of contaminant proteins in the receptor preparations affect the sensitivity and precision of the assay, various chromatographic techniques were tested to improve the purity of the receptor preparation. We found that both G-100 Sephadex and DEAE Sephacel chromatographies were effective in removing contaminant proteins. DEAE Sephacel chromatography is particularly useful because the procedure provides higher recovery of receptor. Against the same pool of autoantibodies from patients with MG, AChRs from diabetic and normal leg muscle exhibit similar affinities. We conclude that AChR from normal human calf muscle can be used in radioreceptor assays for measuring autoantibodies in patients with myasthenia gravis.

Autoantibodies↗

Carcinogenesis bioassays of nickel oxides and nickel-copper oxides by intramuscular administration to Fischer-344 rats.

Five nickel oxides and nickel-copper oxides, with chemical compositions, physicochemical properties, and biological characteristics that were previously reported, were tested for carcinogenicity by administration to groups of male Fischer-344 rats as a single im injection (20 mg Ni/rat). Two additional groups of rats received injections of the glycerol vehicle (Negative Controls) or nickel subsulfide (alpha Ni3S2, 20 mg Ni/rat, Positive Controls). Within the observation period of 2 yr post-injection, the following numbers of sarcomas developed at the injection site: Negative Controls, 0/15; Positive Controls, 15/15; Compound A (INCO black NiO, prepared at less than 650 degrees C), 6/15; Compound B (grey NiO, calcined at 735 degrees C), 0/15; Compound F (green NiO, calcined at 1,045 degrees C), 0/15; Compound H (oxidized Ni-Cu matte, Ni/Cu = 2.5:1, calcined at 850 degrees C), 13/15; Compound I (oxidized Ni-Cu matte, Ni/Cu = 5:1, calcined at 850 degrees C), 15/15. The Ni- and Ni/Cu-oxides that induced sarcomas (Compounds A, H, and I) had measurable dissolution rates in body fluids and were strongly positive in an erythrocytosis stimulation assay, demonstrating Ni bioavailability. Compound A contained detectable Ni[III] and Compounds H and I contained Cu, plus traces of Fe, Co and S, which may all promote oxygen free-radical reactions. In contrast, the compounds that did not induce sarcomas (Compounds B and F) were essentially insoluble in body fluids, did not stimulate erythrocytosis, and were practically devoid of Ni[III], Cu, Fe, Co, or S. Thus, the bioavailability of nickel and the presence of constituents that promote oxygen free-radical reactions evidently influence the carcinogenicity of nickel oxides and related compounds.

Animals↗

Cerebrospinal fluid lipoperoxides quantified by liquid chromatography, and determination of reference values.

Cerebrospinal fluid lipoperoxides, measured as the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct, were quantified by adapting the plasma liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to cerebrospinal fluid. Reference values for spinal fluid specimens from 91 adults, ages 17 to 95 y, and 37 children, ages 8 d to 8 y, were determined. Their concentrations were not significantly different (P = 0.222), adults having a mean (and SD) of 0.11 (0.06) mumol and children 0.10 (0.04) mumol of MDA per liter. Their ranges were 0.02-0.26 and 0.04-0.21 mumol of MDA per liter, respectively. We found concentrations in cerebrospinal fluid to be increased in several central nervous system disorders, including seizures, cerebral infarction, alcoholic encephalopathy, and, perhaps, prematurity. The presence of other thiobarbituric acid-reactive substances in cerebrospinal fluid stresses the importance of using highly specific techniques when lipoperoxides are measured in body fluids.

Adolescent↗

Generalized beta 2-microglobulin deposition. A preamyloidosis disorder?

Generalized beta 2-microglobulin deposition in the tissues of a 64-year-old man with idiopathic end-stage renal disease was determined post mortem by the use of immunoperoxidase and radial immunodiffusion techniques. He developed progressive organ failure secondary to beta 2-microglobulin deposition, requiring dialysis for the last two years of his life. His immediate cause of death was severe bronchopneumonia. The extensive tissular deposits were shown to be congophilic but not birefringent by alkaline Congo red stains. Immunochemical studies showed that the deposits were beta 2-microglobulin-positive but AA amyloid-, P-component-, prealbumin-, and kappa and lambda light chain-negative. We suggest that this patient had a primary beta 2-microglobulin dyscrasia in which beta 2-microglobulin deposited in tissues but did not undergo complete amyloidogenic change.

Amyloidosis↗

Pulmonary histopathology of rats following parenteral injections of nickel chloride.

To elucidate the subacute toxic reactions to parenteral administration of Ni2+, male F-344 rats were given daily injections of NiCl2 (62.5 or 125 mumol/kg, sc) for 3 to 6 weeks. Nickel accumulation was greater in lung than in the other major organs, based upon tissue analyses by electrothermal atomic absorption spectrometry. After 5 or 6 weeks of NiCl2 treatment, severe pathological changes developed in the lungs, including a) prominent hydropic and degenerative changes of the endothelium of pulmonary arteries and veins; b) marked proliferation of alveolar lining cells, affecting Type II (granular)pneumocytes; c) thickening of alveolar walls, with proteinaceous alveolar exudate; d) hyperplasia of bronchial epithelium, with cellular atypia and mitoses; and e) focal bronchial pneumonia with intrabronchial exudates. These pulmonary responses to repeated daily injections of NiCl2 were substantially different from the pathological lesions seen 24 to 72 hours after a single sc injection of NiCl2 (500 or 750 mumol/kg), which included perivascular edema, karyorrhexis and pyknosis of mononuclear cells in focal perivascular infiltrates, and mild pulmonary congestion. This study shows that the lung is a primary site of toxicity in rats following parenteral administration of NiCl2; vascular endothelial cells, Type II pneumocytes, bronchial epithelial cells, and mononuclear cells constitute the principal cellular targets for pulmonary toxicity of Ni2+.

Animals↗

Improved specificity of the CA 125 enzyme immunoassay for ovarian carcinomas by use of the ratio of CA 125 to carcinoembryonic antigen.

We found that ovarian cyst fluids contained carcinoembryonic antigen (CEA) and CA 19-9 and CA 125 tumor markers. However, only the ratio of CA 125 to CEA concentrations provided sufficient specificity to differentiate serous from mucinous cysts. For CEA measurement, our results suggested the use of a monoclonal CEA kit. When CEA was determined with a Hybritech monoclonal CEA kit, all ratios in mucinous ovarian cysts were less than 10 and most of the ratios were greater than 1000 in serous ovarian cysts. We also found that the ratio of CA 125 to CEA in serum could be used to differentiate ovarian from nonovarian malignant diseases when both sera contain increased CA 125 concentrations. The nonovarian malignancies consisted of colorectal, breast, lung, and pancreatic carcinomas. The mean ratio for serum from patients with nonovarian cancers was 0.94 (n = 19); for ovarian-cancer patients (n = 45), 916. Therefore, determining this ratio will greatly improve the specificity of the CA 125 test for ovarian cancer.

Antibodies, Monoclonal↗