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Biomedical subjects

K M Taylor

Publications and source records attributed to K M Taylor.

At least 127 records · Page 7Linked to original sources
PubMed1996

The emerging role of the physician in genetic counselling and testing for heritable breast, ovarian and colon cancer.

As a genetic testing for susceptibility to breast, ovarian and colon cancer becomes more readily available, physicians are faced with an increasing demand for information about inherited cancer risk. Because advances in treatment have not kept pace with advances in predictive testing, the provision of genetic counselling and testing marks a departure from the traditional role of the physician. A systematic framework is needed within which the physician's emerging role in predictive testing for heritable cancer can be delineated. The development of such a framework will require collaboration among professionals in a range of scientific disciplines, as well as the suspension of traditional assumptions about the physicians role.

Breast Neoplasms↗
PubMed1996

Legal and ethical issues in genetic testing and counseling for susceptibility to breast, ovarian and colon cancer.

The prediction of susceptibility to heritable breast, ovarian and colon cancer raises important legal and ethical concerns. Health care professionals have a duty to disclose sufficient information to enable patients to make informed decisions. They must also safeguard the confidentiality of patient data. These duties may come into conflict if a positive finding in one patient implies that family members are also at risk. A legal distinction is made between a breach of confidentiality and the legitimate sharing of information in a patient's interest or to prevent harm to a third party. Physicians also have a fiduciary duty to warn. Other issues concern the legal liability assumed by genetic counsellors, whose disclosures may influence decisions about childbearing, for example, and the risk of socioeconomic discrimination faced by people with a known genetic susceptibility. Traditional ethical orientations and principals may be applied to these and other questions, but feminist ethics will likely have particular importance in the development of an ethical stance toward testing and counseling for heritable breast and ovarian cancer.

Beneficence↗
PubMed1996

A sociobehavioural perspective on genetic testing and counselling for heritable breast, ovarian and colon cancer.

Testing for susceptibility to heritable breast, ovarian and colon cancer has unique psychosocial costs. Negative test results may not be sufficient to relieve anxiety, and positive results can cause sufficient distress to compromise patient compliance with surveillance and risk reduction measures. More needs to be learned about how sociocultural factors affect the understanding of risk, how decisions to undergo testing are made and how information about increased risk affects family dynamics. As the demand for testing and counselling grows, health care providers will be faced with new challenges and dilemmas. A better understanding of genetics by the public is needed to mitigate deterministic attitudes that can lead to the neglect of health promotion. Also of concern are the socioeconomic implications of being identified as having a high risk for heritable cancer and the dangers inherent in using genetics to explain sociological phenomena. Health care providers must take the lead in ensuring that developments in genetics are used to the benefit of all.

Attitude↗
PubMed1996

Effect of cholesterol on the tight insertion of cytochrome b5 into large unilamellar vesicles.

When cytochrome b5 is added to large unilamellar vesicles (LUVs) of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), it binds predominantly in a 'loose,' or transferable form. Prolonged incubation of 30 degrees C leads to insertion in the physiological 'tight,' nontransferable form, with a halftime for the loose --> tight conversion of approx. 9 days. In this study, the effect of cholesterol on the rate of tight insertion was determined. Tight binding was assayed by depleting the LUVs of loose cytochrome b5 with an excess of SUV acceptors and then separating the liposome populations by gel-filtration or velocity sedimentation. Incorporation of cholesterol into the LUVs was found to markedly increase the rate of tight insertion, even though cholesterol decreases the equilibrium binding constant and saturation level of protein binding. The effect is not a continuously increasing function of cholesterol content, but attains a maximum at 20-25% mol%, where the rate enhancement is approx. 10-fold over baseline. At higher cholesterol levels, the rate decreases, returning to baseline at 40 mol% cholesterol. These observations are highly unusual in that cholesterol generally decreases the membrane binding affinity and the permeability of solutes, and does so as a monotonic function of cholesterol concentration (above the liquid-crystalline phase transition of the phospholipids). It is suggested that tight insertion is enhanced by lipid-protein packing mismatches and by bilayer fluidity; the former increases monotonically with increasing cholesterol whereas the latter decreases monotonically. At 20-25 mol% cholesterol the optimum balance of these physical properties is obtained for tight insertion.

Centrifugation, Density Gradient↗
PubMed1996

Validation of the Applied Biosystems Prism 377 automated sequencer for the forensic short tandem repeat analysis.

The Applied Biosystems (ABI) Prism 377 DNA sequencer has been evaluated in an attempt to increase the throughput of samples for short tandem repeat (STR) analysis, in both forensic casework and the UK National Criminal Intelligence DNA Database. The gel system assessed consisted of 0.2 mm, 4% acrylamide 6 M urea gels, with a well-to-read distance of 36 cm. Gels were run at a constant voltage of 3 kV and constant temperature of 51 degrees C. The run time of our second generation multiplex (SGM) STR system was achieved in less than 2 h. Rigorous validation has been performed on the instrument hardware and software. Complete resolution of 1 base differences was obtained, up to and beyond 350 bases; sizing precision across gels was more than 2-fold higher than the 373A and the sensitivity was increased by one third.

Autoanalysis↗
PubMed1996

Physicians' perspective on quality of life: an exploratory study of oncologists.

There is an implicit assumption that physicians incorporate quality of life (QOL) information in clinical decision-making. However, very limited data exists on how physicians view QOL information and how they actually use it. To explore this issue, an in-depth study was conducted using a semi-structured interview guide, with 60 oncologists in Canada and the USA. While the majority of respondents perceived QOL as important they reported a tendency to use it informally and not in all situations. Key findings include the belief expressed by 88% of respondents that the term QOL could be defined, although they differed in their definitions. Although 85% stated that QOL can be formally measured, only a third perceived that the current instruments provide valid and reliable data. Respondents noted a number of significant benefits and drawbacks of using QOL data in their clinical practice that had not been previously noted in the literature. For example, its use as an endpoint in clinical trials was generally perceived to enhance both physician and patient participation. A drawback noted was that including QOL might adversely affect the decision-making process. These findings have been used to develop a self-administered questionnaire (MD-QOL) which will test the generalizability of these findings.

Adult↗
PubMed1996

Genetically engineered serine protease inhibitor for hemostasis after cardiac operations.

BACKGROUND: The serine protease inhibitor aprotinin has been widely reported for its beneficial action in limiting blood loss after cardiopulmonary bypass (CPB). A potent human serine protease inhibitor known as protease nexin II or amyloid precursor protein has been recently isolated. A recombinant protein known as recombinant Kunitz protease inhibitor (rKPI; Scios Nova, Mountain View, CA) with sequence homology to the protease nexin II-amyloid precursor protein molecule has been manufactured. METHODS: Recombinant Kunitz protease inhibitor was assessed in an ovine model of CPB as a hemostatic agent after CPB. Sheep (n = 22) underwent CPB for 90 minutes. Two thoracic drains were sited and drain losses collected for a period of 3 hours after CPB. Wounds were subjectively assessed before closure for "dryness" using a visual analogue scale. Sheep were randomized to control (n = 8), aprotinin (n = 8), and rKPI (n = 6) groups. RESULTS: Control animals had a drain loss of 409.4 +/- 39.4 mL/3 h, compared with 131.3 +/- 20.3 mL/3 h for the aprotinin group and 163.7 +/- 34.3 mL/3 h for the rKPI group (p = 0.16). Hemoglobin loss was 11.6 +/- 3.6, 6.02 +/- 2.1, and 4.6 +/- 1.2 g/3 h for the control, rKPI, and aprotinin groups respectively (p = 0.25). The subjective analysis of the wounds at the end of CPB found aprotinin (1.25 +/- 0.16; p < 0.05) and rKPI (1.17 +/- 0.17; p < 0.05) animals to score significantly lower than control animals (2.63 +/- 0.42). CONCLUSIONS: On the basis of these in vivo findings, genetic modification may yield a more efficacious serine protease inhibitor with the inherent advantages of using a human-based protein.

Animals↗
PubMed1996

Morphine and naloxone, i.p. or locally, affect extracellular acetylcholine in the accumbens and prefrontal cortex.

In rats with microdialysis probes in the nucleus accumbens (NAc) or prefrontal cortex (PFC), intraperitoneally (IP) delivered morphine on the 8th day of escalating doses decreased extracellular ACh in the NAc. On day 9, naloxone (5 mg/kg) precipitated withdrawal and increased the release of ACh. When morphine and methylnaloxonium were given locally into the NAc by reverse dialysis, the opiate again decreased extracellular ACh, and the opiate antagonist increased it. These effects were proportional to the dose of local infusions. Local morphine had the same ACh-lowering effect in morphine-dependent and nondependent rats, whereas local methylnaloxonium increased extracellular ACh significantly more in morphine-dependent animals. Systemic and local effects on ACh systems in the PFC were more complicated and showed some relation to locomotor activity. The results suggest that intrinsic ACh neurons in the NAc have a special relationship to opiate reinforcement such that extracellular ACh is low in response to morphine and high during withdrawal. Thus, low ACh may correlate with opiate reward, and high ACh with aversion.

Acetylcholine↗
PubMed1996

A pharmacokinetic study of sublingual aerosolized morphine in healthy volunteers.

A pharmacokinetic study was undertaken to compare the pharmacokinetics of morphine after an intravenous dose with the pharmacokinetics after a sublingual dose administered from an aerosol. Plasma levels of morphine, morphine-3-glucuronide and morphine-6-glucuronide were measured in five normal volunteers after morphine administration by the intravenous route and from a novel sublingual pressurized aerosol formulation. The mean (+/- s.d.) bioavailability of the sublingual aerosol morphine was 19.7 +/- 6.7%. The morphine-3-glucuronide/morphine and the morphine-6-glucuronide/morphine ratios were 5.1 +/- 1.6 and 1.2 +/- 0.4, respectively, for the intravenous route and 28.3 +/- 11.3 and 5.2 +/- 1.4, respectively, for the sublingual route. The combined total areas under the plots of systemic concentration against time (AUC) for the metabolites after the two routes was not significantly different. When compared with published data for oral administration the results demonstrate that the sublingual aerosol morphine might provide an alternative to conventional methods of morphine delivery, and has similar pharmacokinetics to a sublingual morphine tablet. It has no particular pharmacokinetic advantages over oral morphine, except a potential for a faster onset of analgesia. Bioavailability, maximum plasma concentration, Cpmax, and the time at which the maximum plasma concentration is reached, Tmax, are equivalent to those for orally administered morphine.

Administration, Sublingual↗
PubMed1996

Granulocyte colony stimulating factor treatment for alloimmune neonatal neutropenia.

Granulocyte colony stimulating factor (G-CSF) treatment was successfully used in three preterm infants with alloimmune neonatal neutropenia (AINN). Two infants had persistent neutropenia despite treatment with intravenous immunoglobulin and random donor granulocyte transfusions for presumed sepsis. Neutrophil counts returned to normal with G-CSF treatment; the response was least convincing in one infant with fulminant necrotising enterocolits. It is suggested that treatment with G-CSF be considered early for the treatment of infants with AINN.

Antibodies↗