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Biomedical subjects

C D Cook

Publications and source records attributed to C D Cook.

At least 19 recordsLinked to original sources

Effects of the delta opioid against BW373U86 in pigeons trained to discriminate fentanyl, bremazocine and water in a three-choice drug discrimination procedure.

The delta opioid agonist BW373U86 was examined alone and in combination with mu agonists in pigeons trained to discriminate the mu agonist fentanyl (0.056 mg/kg), the kappa agonist bremazocine (0.017 mg/kg), and distilled water in a three-choice drug discrimination procedure. BW373U86 (0.01-10 mg/kg) produced a dose-dependent increase in fentanyl-appropriate responding and complete generalization to fentanyl in four of five subjects. BW373U86 did not elicit bremazocine-appropriate responding in any of the subjects. Fentanyl-appropriate responding elicited by BW373U86 was antagonized by the delta selective antagonist naltrindole (0.1-10 mg/kg) but not by the mu selective antagonist naloxone (0.1-30.0 mg/kg). When BW373U86 was administered in combination with the mu agonists fentanyl, morphine and nalbuphine, a low dose of BW373U86 (0.01 mg/kg) that elicited primarily water-appropriate responding when administered alone did not produce a significant change in the ED50 values for fentanyl, morphine or nalbuphine. Higher doses of BW373U86 (0.1-1.0 mg/kg) increased levels of fentanyl-appropriate responding elicited by low doses of fentanyl, morphine and nalbuphine to levels similar to those produced by BW373U86 alone. These results indicate that BW373U86 shares discriminative stimulus properties with the mu agonist fentanyl in pigeons, possibly by acting at delta opioid receptors. However, BW373U86 does not potentiate the discriminative stimulus effects of mu agonists or share discriminative stimulus effects with the kappa agonist bremazocine.

Analgesics

The expert witness: real issues and suggestions.

Medical malpractice lawsuits generally require expert testimony. Defendants and plaintiffs deserve expert testimony that is exacting, accurate, and consistent. A study of four frequently testifying experts was undertaken with review of depositions, reports, and trial transcripts of those experts. Contradictions in claimed medical principles from one case to the next were found and examples were cited for each expert. The review suggested that expert testimony regarding the standard of care may be neither reliable nor accurate for the purposes of judging physician conduct is lawsuits. Presently, no peer review or sanction process has been implemented to ensure accuracy and reliability of expert testimony used in medical malpractice lawsuits. We recommend changes that would include independent court-appointed experts, central filing of opinion letters by experts with authoritative text citations, and a sanction process by courts and/or authorized boards for testimony that is deemed inaccurate, false, or contradictory to the standard of care.

Expert Testimony

Prevalence and incidence of blindness due to age-related cataract in the rural areas of South Africa.

OBJECTIVES: The Bureau for the Prevention of Blindness is responsible for the provision of cataract surgery to the rural indigent population of South Africa. It is important for the Bureau to know both the prevalence and the incidence of cataract blindness in the population. DESIGN, SETTING AND SUBJECTS: Blindness prevalence surveys were conducted in KwaZulu in 1990 and 1993. OUTCOME MEASURES AND RESULTS: The prevalence of cataract blindness was 0.59% (95% confidence interval 0.21) in 1990 and 1993. The prevalence of aphakia was 0.1% in 1990 and 0.2% in 1993, demonstrating a probable increase in the delivery of cataract surgical services, although this had not produced a demonstrable fall in the prevalence of cataract blindness. The calculated annual incidence of cataract blindness was 0.14%. CONCLUSION: Among a rural population of approximately 19 million South Africans, there is a backlog of 113,000 unoperated cataract-blind people and an incidence of 27,000 new cataract blind per year. The implications of this backlog for cataract blindness in our rural areas are discussed.

Age Factors

Impact of a sight-saver clinic on the prevalence of blindness in northern KwaZulu.

The prevalence of blindness in the Ingwavuma district of northern KwaZulu was 1% (95% confidence interval 0.75 - 1.25) in 1990, and the prevalence of blindness due solely to age-related cataract was 0.39% (95% CI 0.24 - 0.54). Eight sight-saver clinics were held between 1990 and 1993. Nine hundred and thirteen patients were seen and 113 cataract extractions performed at a cost of R62,000. The prevalence of blindness due solely to age-related cataract was reduced by 25% to 0.29% (95% CI 0.17 - 0.41). The overall prevalence of blindness was reduced by 4% to 0.96% (95% CI 0.72 - 1.20). The provision of aphakic spectacles to aphakic patients whose spectacles have either been lost or broken would effect a further 11% reduction to 0.85% (95% CI 0.63 - 1.07). The establishment of a permanent sight-saver clinic staffed by an ophthalmic medical assistant who is working full-time in this capacity would facilitate an improvement in the delivery of eye care in the area.

Age Factors

Prevalence and causes of low vision and blindness in northern KwaZulu.

A survey of the prevalence of blindness and low vision was conducted in the Ingwavuma district of KwaZulu to assess the effectiveness of existing eye care facilities in the prevention and treatment of impaired vision and blindness. One hundred subjects from each of 60 randomly selected clusters (N = 6,090) were screened. Of these, 293 were identified and referred to an ophthalmologist for examination. Of the 268 (91,5%) examined, 241 were found to have visual impairment. Sixty-one of these people were blind, 85 had low vision, 61 were blind in one eye but had normal vision in the other, and 34 had low vision in one eye but normal vision in the other. The prevalence of blindness was 1,0% (95% confidence interval 0,7-1,2%), and the prevalence of impaired vision was 1,4% (95% confidence interval 1,1-1,7%). Age-related cataract (59,0%) and chronic glaucoma (22,9%) were the two main causes of blindness. Age-related cataract (75,3%), refractive error (10,0%) and chronic glaucoma (4,7%) were the main causes of impaired vision. Existing eye care services for the region have reduced the prevalence of blindness by only 7,0%. The training of ophthalmic nurses and the establishment of a sight-saver clinic in the area are necessary to reduce the prevalence of low vision and blindness.

Adolescent

Thrombomodulin activity and localization.

An overview on the properties, actions and localization of thrombomodulin (TM) in situations of tissue injury and in selected tumors is presented. The localization and activity of TM after injury to vascular endothelium shows that following balloon catheter denudation of the endothelium of the rabbit aorta, the activity and immunohistochemical staining is markedly reduced. The functional and antigenic levels approach the control levels approximately one week after the initial injury. The results suggest that the neointimal smooth muscle cells express TM. This phenotypic plasticity of the neointimal smooth muscle cells may be important in conferring thrombo-resistance to the lumenal lining cells of vessels after injury. Studies are also reviewed on the use of soluble recombinant TM to prevent thrombosis after ligature of vessels in an experimental model. Further characterization on the immunohistochemical distribution of TM in normal tissues and tumors shows that staining with a monoclonal anti TM antibody can be very useful in separating mesotheliomas from pulmonary adenocarcinomas. These studies may lead to insights concerning the role of TM in tissue-injury-repair and tissue differentiation.

Adenocarcinoma

Thrombomodulin expression in malignant pleural mesothelioma and pulmonary adenocarcinoma.

Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.

Adenocarcinoma

Perforating eye injuries in KwaZulu.

Data on 100 consecutive perforating eye injuries treated at Edendale Hospital, Pietermaritzburg, were collected in order to evaluate some of the features of this condition seen in KwaZulu, and also to assess the outcome of current management. Fifty-six of the injuries were due to assault and 44 were accidental. Fifty injuries involved the anterior segment only, and 50 involved the posterior segment. Only 6 eyes achieved a final visual acuity of 6/12 or better, and 44 eyes ended up with no light perception. Factors contributing to the poor visual results in this Third-World situation include the severity of the injuries and the inadequacy of surgical management within the constraints imposed by limited facilities and expertise. More care is needed in selecting patients with posterior segment injuries, in whom useful ambulatory vision may be salvageable, for vitrectomy and retinal detachment repair. The criteria for such selection should include the nature of the injury, the visual acuity, the presence or absence of an afferent pupil defect, the extent of the injury found at the time of repair, the presence and extent of vitreous haemorrhage, and the findings on ultrasonography.

Adolescent

Thrombomodulin activity on human saphenous vein grafts prepared for coronary artery bypass.

Thrombomodulin, a membrane glycoprotein present on normal vascular endothelium, binds circulating thrombin and is important in protein C activation. These functions contribute to the nonthrombogenic nature of endothelium. Damage during harvest and ex vivo storage of vein grafts may result in dysfunction of this endothelial anticoagulant barrier and possibly contribute to early graft thrombosis. We studied the functional activity and antigenic expression of thrombomodulin on saphenous veins before (initial) and after (harvested) harvest and storage for coronary artery bypass grafting in 15 patients. Also, fresh saphenous vein was studied after mechanical endothelial stripping. After storage for 2.7 +/- 0.6 hours at room temperature in heparinized saline, thrombomodulin functional activity in harvested vein segments was 28% less than initial segments (p = 0.08). Endothelial stripping resulted in a 79% reduction in thrombomodulin activity compared with initial segments (p = 0.04). Immunohistochemical staining confirmed thrombomodulin antigen on vein grafts after harvest and storage, but not on segments stripped of endothelium. Thrombomodulin functional activity and antigenic expression on human saphenous vein grafts is not significantly changed by harvest and relatively short periods of storage at room temperature in heparinized saline.

Antigens

Tuberculosis of the conjunctiva occurring in association with a neighbouring lupus vulgaris lesion.

A case of tuberculosis of the conjunctiva in association with a neighbouring lupus vulgaris lesion is reported. Both lesions resolved within one month of starting antituberculous therapy. Tuberculosis of the conjunctiva is nowadays a rare condition. It should be considered in the differential diagnosis of any unusual chronic conjunctivitis, particularly in patients who are at risk of contracting tuberculosis.

Adult

Clinical algorithms teach pediatric decisionmaking more effectively than prose.

Despite the rapidly increasing volume of medical literature, little attention has been paid to the appropriate printed format for teaching clinical content. This study attempted to determine whether a clinical algorithm (CA) or prose is more effective for teaching clinical decisionmaking. Clerkship students, preclerkship students, and pediatric house officers in five medical centers in the USA and Israel were presented with clinical algorithms and prose describing management of fever in a child under 2 years of age, and management of meningitis in children. Knowledge of decisionmaking was measured before and after learning, using audio-taped clinical problems and learning time as measured. It was concluded that CAs are more effective and more efficient than prose for teaching clinical decisionmaking. When writing about clinical decisionmaking, the use of CAs should always be considered, especially if a series of interdependent decisions is being described.

Algorithms

Moral reasoning and decisions in dilemmas of neonatal care.

The relationship between levels of moral reasoning and decisions in dilemmas of neonatal care was investigated in a sample of 452 pediatricians. Subjects included residents, faculty members, and practitioners recruited from a variety of university-affiliated and community hospitals. It was hypothesized that physicians whose moral reasoning was more fully developed would less actively treat particular cases. Such cases might include those where a patient's family requested such a limit (designated "negative family attitude") or the quality of life likely to be led after therapy was so low as to preclude even a minimal degree of human activity or social interaction (designated "unsalvageable prognosis"). The hypothesis was tested through the use of two questionnaires. The first questionnaire, devised by Crane, assessed the physician's reported degree of activism in treating six cases of infants born with severe defects. The structure of moral reasoning was measured by a second questionnaire, Rest's Defining Issue Test. Subjects were scored by the degree to which they use universal, ethical principles in resolving a series of moral dilemmas. Results of the absolute level of activism (Table 1) showed that among both residents and postresidents, the degree to which cases are actively treated depends, for salvageable patients, on the type of damage and on the possibility for research. Results involving moral reasoning showed a different pattern among residents and postresidents. Among residents, a significant correlation exists between principled reasoning and the absence of active treatment (r = - 0.41, Form A; r = - 0.23, Form B). As predicted, such correlations were strongest for cases of negative family attitude or of unsalvageable prognosis. The pattern of correlations among postresidents showed either no relationship to moral reasoning or the reverse of the residency pattern (r = -0.08, Form A; r = 0.30, Form B). The influence of the type of institution a resident operates within was assessed by analysis of variance. Inasmuch as moral reasoning and institutional type both had significant main effects (Form A), their magnitude differed. Institutional type accounted for 43% of the variation in mean activism scores whereas moral reasoning accounted for only 4%; however, because one could, a priori, expect institutional norms and customs to be powerful determinants of behavior, any additional, identifiable influence deserves attention. The structure of individuals' moral reasoning seems to be such an influence.

Attitude of Health Personnel