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Biomedical subjects

D King

Publications and source records attributed to D King.

At least 199 records · Page 11Linked to original sources

Viral inactivation in blood and red cell concentrates with benzoporphyrin derivative.

Using both the vesicular stomatitis virus (VSV) and feline leukemia virus (FeLV) as models we have shown that the photosensitizer benzoporphyrin derivative ring A (BPD), when activated with red light (600-700 nm), is effective in eliminating both free virus and virally infected cells from spiked blood products and whole blood drawn from viremic cats experimentally infected with FeLV, under conditions which appear to share red blood cells. The effect of photodynamic therapy on infected lymphocytes, as visualized by scanning electron microscopy, initially appeared as a limited area of tiny holes in the membrane. These holes were subsequently seen to increase in size until the membrane appeared completely decomposed. The red cell membranes however, seem to be undamaged by such photodynamic treatment.

Animals↗

Doctors' knowledge of socio-legal aspects of patient care.

Doctors' knowledge of socio-legal aspects of patient care is poor. To quantify this a questionnaire on certain socio-legal topics was sent to 400 general practitioners and 250 hospital doctors. The responses were compared to a group of social workers. Both hospital doctors and general practitioners did badly on all topics considered. Social workers' knowledge was significantly better overall, (P < 0.01). Our results confirm the lack of knowledge amongst a broad spectrum of doctors. We suggest that this may be related to a lack of emphasis on these aspects in both undergraduate and postgraduate education.

Aged↗

Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans.

Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa light chain, was administered as a 131I-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t 1/2 of 18 +/- 7 h and a beta t 1/2 of 224 +/- 66 h. A second infusion of the same dose of 131I-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free 131I in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions.

Animals↗

Pressurised aerosol inhalers: the cost of misuse.

Bronchodilator aerosols, if used correctly, have many advantages over other therapies in patients with chronic airflow limitation caused by asthma or chronic bronchitis. The use of pressurized aerosol inhalers was examined in a district general hospital: of 57 patients on these inhalers, 39 were unable to use the inhaler effectively, and 23 had never received any advice on inhaler technique. A single demonstration of correct technique decreased the failures to 21 patients and, after two demonstrations, to ten. The cost of the misused inhalers in this relatively small population was 450 pounds, and obviously this figure escalates when the prescription for these inhalers is repeated monthly. It is also increased when the total numbers of misused inhalers in the country are accounted for. The cost in terms of finance, in these days of medical audit and drug budgets, and, more importantly, in terms of patient health, is unacceptable and can be avoided by repeated tuition of technique.

Adult↗

Direct sequencing of PCR-amplified junction fragments from tandemly repeated transgenes.

When microinjected foreign genes integrate into the genomes of mice, multiple copies are frequently found clustered together at one location. How they concatamerize--by the integration of large linearized concatamers that are formed by simple end-to-end linkage, by circularization of individual DNA fragments and recombination, or by some other means--is not understood. In the transgenic animals studied thus far by ourselves and others, integration frequency and transgene copy number do not seem to be significantly influenced by the complementarity of the ends of the DNA fragments that have been microinjected. We have utilized PCR amplification and DNA sequence analysis to study selected transgene junctions at the nucleotide level. In two transgenic mice carrying the synthetic RSVcat gene (injected with noncomplementary overhangs on the fragment ends), ends were 'nibbled' from 1 to 62 bases before being joined to an adjacent gene copy. Repeated dinucleotides, providing the most minimal of homologies, are present in half of the characterized junctions. Determination of the relative copy number of the junctions in each mouse supports the idea that transgene complexes can undergo additional rearrangements after the initial formation event.

Animals↗

Establishment of immortalized primate epithelial cells with sub-genomic EBV DNA.

The genetic information in a sub-fragment of EBV DNA, designated p31 (containing less than a quarter of the viral genome and derived from a recombinant DNA cosmid library) allows epithelial cells from primary monkey and human kidney cultures to escape senescence under standard tissue culture conditions. A number of epithelial cell lines, designated M1/31, 483/31, 199/31 and HK/31, have been established and characterized following transfection of primary cells with p31 DNA. They share many properties, although morphologically they are not all identical. The cultures are immortalized but not fully transformed or tumorigenic. They appear to be phenotypically stable, although DNA hybridization studies indicate that genotypic alterations, including amplification, occur subsequent to transfection with p31 DNA and the establishment of a continuously proliferating epithelium. All cell lines consistently express high levels of cytokeratin 18 and varying amounts of cytokeratin 7, demonstrating their epithelial origin. From a single marmoset kidney (designated 199) a series of related immortalized cells, with subtle phenotypic differences, have been generated by p31 or sub-fragments of it. Although hallmarks of a "hit-and-run" mechanism are apparent in all of our studies, 2 different techniques (in situ hybridization or selection for cell survival in semi-solid media, followed by nucleic acid hybridization) show that, in late-passaged cultures, a small proportion of the cells still contain some viral DNA. The studies focus on genetic information within the BamHI A and I regions as being relevant to immortalization. The role of the EBV DNA fragment in the genesis of epithelial cell lines is considered.

Animals↗

Small increases in circulating luteinizing hormone (LH) concentrations shortly before human chorionic gonadotropin (hCG) are associated with reduced in vitro fertilization (IVF) pregnancy rate.

The effects of slight elevations in serum LH just before hCG administration on IVF cycle outcome were studied in 219 women undergoing retrieval. One hundred seven patients were stimulated using human menopausal gonadotropin (hMG), and 112 received clomiphene citrate and hMG. Serum LH, estradiol (E2), and progesterone concentrations were measured before and during controlled ovarian stimulation. Retrospectively the women were subdivided into three groups based on serum LH before hCG: Group I, less than 50% LH rise from baseline (BL) value (mean of day 2 and day 7); Group II, LH rise greater than or equal to 50% but less than 2 x BL; and, Group III, LH rise greater than or equal to 2 x BL. The fertilization and cleavage rates were similar in all groups. However, a greater than or equal to 50% rise in serum LH before hCG was associated with a significantly reduced IVF pregnancy rate.

Chorionic Gonadotropin↗

Lung management during cardiopulmonary bypass: influence on extravascular lung water.

Progressive respiratory insufficiency secondary to cardiopulmonary bypass (CPB) is still a hazard after cardiac surgery. Pathophysiologically, impaired capillary endothelial integrity seems to be the fundamental lesion, followed by increased interstitial fluid accumulation. The reasons for this pulmonary damage are controversial; however, management of the nonperfused lungs during CPB has been widely neglected and may be partly responsible. In this study, 90 patients undergoing coronary artery bypass grafting were randomly divided into six groups (15 patients each) with different management of the lungs during CPB: group 1, lungs collapsed (0/0); group 2, static inflation with +5 cm H2O and F1O2 1.0 (+5/1.0); group 3, static inflation with +5 cm H2O and F1O2 0.21 (+5/0.21); group 4, static inflation with +15 cm H2O and F1O2 1.0 (+15/1.0); group 5, static inflation with +15 cm H2O and F1O2 0.21 (+15/0.21); and group 6, controlled mechanical ventilation as before start of CPB (positive end-expiratory pressure [PEEP] +5 cm H2O; F1O2 1.0) (ventilation). In addition to hemodynamic monitoring, extravascular lung water (EVLW) was measured by means of a double-indicator dilution technique with heat and indocyanine green. Measurements were performed after induction of anesthesia, before onset of CPB, and immediately after weaning from bypass, as well as 60 minutes and 5 hours after termination of CPB. Pulmonary gas exchange (PaO2) and intrapulmonary shunting (Qs/Qt) were also measured. Starting from comparable, normal baseline values, EVLW was increased in all groups after weaning from CPB, with the most pronounced increase in group 4 (maximum, +35%) and group 5 (+40%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Response of oral leukoplakia to beta-carotene.

Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta-carotene. Therefore, the study design was changed to a phase II trial of beta-carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer.

Aged↗

"Prostitutes as pariah in the age of AIDS": a content analysis of coverage of women prostitutes in The New York Times and the Washington Post September 1985-April 1988.

Misrepresentation in the media portrays women prostitutes as sexual transmitters of AIDS to men. Yet careful study of the available data shows male-to-female transmission of the HIV virus is the overwhelming mode of heterosexual transmission of AIDS. Content analysis is performed to analyze the role newspaper coverage played from 1985 through early 1988 in the social construction of prostitutes as a new target group for AIDS. The results show little concern for the health of prostitutes at risk for AIDS, but rather for their role as possible disease vectors. That women prostitutes were eagerly singled out as a target group despite a dearth of evidence points in large measure to their precarious position in society. And it highlights the impact media has when it acts as an uncritical sounding-board for government and medical press releases about a disease with dire social as well as physical consequences.

Acquired Immunodeficiency Syndrome↗

Acquisition and maintenance of exercise skills under normalized conditions by adults with moderate and severe mental retardation.

Three older adults with severe and moderate mental retardation were taught a complete regimen of aerobic-type exercises under conditions that approximated mainstream exercise programs. A treatment package (prompts, contingent praise, and delayed reinforcing activities) was implemented by individual coaches while participants followed the instructions of an exercise leader. Prompts were faded and contingent activities were discontinued following skill acquisition. All participants correctly performed between 63% and 85% of the exercise repetitions during training and between 82% and 95% at a 9-month follow-up. Issues and strategies for achieving integration of persons with mental retardation into mainstream leisure activities were discussed.

Adult↗

Perceptions of clinical decision making by dietitians and physicians.

Role delineation is an ongoing process and must be evaluated within the health care team framework. The specific interactions between dietitians and physicians in the nutrition care of patients is one aspect that needs to be more clearly defined. This study examined selected practice issues by surveying physicians and dietitians to identify perceptions of ideal and actual performance. Role disparity was found between the responses of the dietitians and those of the physicians. Dietitian respondents identified themselves as the primary decision makers more than 50% of the time in all circumstances queried. In contrast, 10% or less of the MDs saw the dietitians as the primary decision makers in any area except selection of caloric supplements. In the ideal setting, the dietitian desired a greater degree of autonomy than the physician was willing to grant. Our findings were not explained by demographic differences. Perhaps faulty communication between the physician and the dietitian or unclear medical-legal issues may explain our findings of perceived role disparity.

Decision Making↗