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Biomedical subjects

J McKie

Publications and source records attributed to J McKie.

16 recordsLinked to original sources
PubMed2001

Thinking about possible people: a comment on Tooley and Rachels.

Most people believe it would be wrong to bring a child into the world if in all likelihood its life would be miserable. But if pain and suffering count against bringing someone into existence, why do pleasure and happiness not count in favour of bringing them into existence? Recently in this journal Michael Tooley has re-affirmed his rights-based explanation for this asymmetry. In a nutshell: to create an individual whose life is not worth living would be to wrong that individual--to create an obligation that cannot be fulfilled--but it is not possible to wrong an individual who is not brought into existence. In the same issue of this journal, in an article covering a range of arguments for and against the claim that it would be good for additional people to exist, Stuart Rachels objects to Tooley's account on the ground that it has counterintuitive implications. His most interesting argument involves a Parfit-style counterexample: a woman is about to take a fertility pill that will result in twins, one of whom will be healthy and the other of whom will not. Does it make a difference, morally speaking, if the woman knows which of the twins will be healthy and which will not? In this paper I argue that both Rachels' criticism of Tooley's rights-based account, and Tooley's own defence of it, are unsuccessful due to their failure to come to grips with the semantics of names for possible individuals. Both of them implicitly assume that it is possible to have a potential person in mind, in a way that misleads them about the fairness of actions that involve possible people. The significance of this extends to other areas such as abortion, population policy, and embryo experimentation, where examples involving possible people are common.

Persons with Disabilities↗
PubMed2000

ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin- 3-yl)pyrido[2,3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory properties. II. In vivo characterization in the rat.

Adenosine kinase (AK; EC 2.7.1.20) is a key intracellular enzyme regulating intra-and extracellular concentrations of adenosine (ADO), an endogenous neuromodulator, antinociceptive, and anti-inflammatory autocoid. AK inhibition provides a means of potentiating local tissue concentrations of endogenous ADO, and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agents. The effects of ABT-702, a novel, potent (IC(50) = 1.7 nM), and selective non-nucleoside AK inhibitor were examined in rat models of nociception and acute inflammation. ABT-702 was orally effective and fully efficacious to suppress nociception in a spectrum of pain models in the rat, including carrageenan-induced thermal hyperalgesia, the formalin test of persistent pain, and models of nerve injury-induced and diabetic neuropathic pain (tactile allodynia after L5/L6 spinal nerve ligation or streptozotocin injection, respectively.) ABT-702 was especially potent at relieving inflammatory thermal hyperalgesia (ED(50) = 5 micromol/kg p.o.). ABT-702 was also effective in the carrageenan-induced paw edema model of acute inflammation (ED(50) = 70 micromol/kg p.o.). The antinociceptive and anti-inflammatory effects of ABT-702 were blocked by selective ADO receptor antagonists, consistent with endogenous ADO accumulation and ADO receptor activation as a mechanism of action. The antinociceptive effects of ABT-702 were not blocked by the opioid antagonist naloxone. In addition, ABT-702 showed less potential to develop tolerance to its antinociceptive effects compared with morphine. ABT-702 had no significant effect on rotorod performance or heart rate (at 30-300 micromol/kg p.o.), mean arterial pressure (at 30-100 micromol/kg p.o.), or exploratory locomotor activity (at </=10 micromol/kg p.o.). Thus, ABT-702 is a novel, non-nucleoside AK inhibitor, with a nonopioid, non-nonsteroidal anti-inflammatory drug mechanism of action, which shows antinociceptive and anti-inflammatory activity in vivo.

Adenosine Kinase↗
PubMed1997

Molecular definition of 22q11 deletions in 151 velo-cardio-facial syndrome patients.

Velo-cardio-facial syndrome (VCFS) is a relatively common developmental disorder characterized by craniofacial anomalies and conotruncal heart defects. Many VCFS patients have hemizygous deletions for a part of 22q11, suggesting that haploinsufficiency in this region is responsible for its etiology. Because most cases of VCFS are sporadic, portions of 22q11 may be prone to rearrangement. To understand the molecular basis for chromosomal deletions, we defined the extent of the deletion, by genotyping 151 VCFS patients and performing haplotype analysis on 105, using 15 consecutive polymorphic markers in 22q11. We found that 83% had a deletion and >90% of these had a similar approximately 3 Mb deletion, suggesting that sequences flanking the common breakpoints are susceptible to rearrangement. We found no correlation between the presence or size of the deletion and the phenotype. To further define the chromosomal breakpoints among the VCFS patients, we developed somatic hybrid cell lines from a set of VCFS patients. An 11-kb resolution physical map of a 1,080-kb region that includes deletion breakpoints was constructed, incorporating genes and expressed sequence tags (ESTs) isolated by the hybridization selection method. The ordered markers were used to examine the two separated copies of chromosome 22 in the somatic hybrid cell lines. In some cases, we were able to map the chromosome breakpoints within a single cosmid. A 480-kb critical region for VCFS has been delineated, including the genes for GSCL, CTP, CLTD, HIRA, and TMVCF, as well as a number of novel ordered ESTs.

Abnormalities, Multiple↗
PubMed1996

Double jeopardy, the equal value of lives and the veil of ignorance: a rejoinder to Harris.

Harris levels two main criticisms against our original defence of QALYs (Quality Adjusted Life Years). First, he rejects the assumption implicit in the QALY approach that not all lives are of equal value. Second, he rejects our appeal to Rawls's veil of ignorance test in support of the QALY method. In the present article we defend QALYs against Harris's criticisms. We argue that some of the conclusions Harris draws from our view that resources should be allocated on the basis of potential improvements in quality of life and quantity of life are erroneous, and that others lack the moral implications Harris claims for them. On the other hand, we defend our claim that a rational egoist, behind a veil of ignorance, could consistently choose to allocate life-saving resources in accordance with the QALY method, despite Harris's claim that a rational egoist would allocate randomly if there is no better than a 50% chance of being the recipient.

Australia↗
PubMed1996

Another peep behind the veil.

Harris argues that if QALYs are used only 50% of the population will be eligible for survival, whereas if random methods of allocation are used 100% will be eligible. We argue that this involves an equivocation in the use of "eligible", and provides no support for the random method. There is no advantage in having a 100% chance of being "eligible" for survival behind a veil of ignorance if you still only have a 50% chance of survival once the veil is lifted. A 100% chance of a 50% chance is still only a 50% chance. We also argue that Harris provides no plausible way of dealing with the criticism that his random method of allocation may result in the squandering of resources.

Australia↗
PubMed1995

Cloning and mapping of murine Nfe2l1.

The murine homologue of the human NFE2L1 basic leucine-zipper gene was isolated from an early embryo library. The deduced amino acid sequence shows 97% identity between the two proteins. Significant sequence similarity is also seen with the p45 subunit of NF-E2 and with the Drosophila CNC protein. Murine Nfe2l1 maps to chromosome 11DE with similar sequence at 7D1-7F1 and 2E4-2G.

Amino Acid Sequence↗
PubMed1995

Double jeopardy and the use of QALYs in health care allocation.

The use of the Quality Adjusted Life-Year (QALY) as a measure of the benefit obtained from health care expenditure has been attacked on the ground that it gives a lower value to preserving the lives of people with a permanent disability or illness than to preserving the lives of those who are healthy and not disabled. The reason for this is that the quality of life of those with illness or disability is ranked, on the QALY scale, below that of someone without a disability or illness. Hence we can, other things being equal, gain more QALYs by saving the lives of those without a permanent disability or illness than by saving the lives of those who are disadvantaged in these ways. But to do so puts these disadvantaged people under a kind of double jeopardy. Not only do they suffer from the disability or illness, but because of it, a low priority is given to forms of health care that can preserve their lives. This, so the objection runs, is unjust or unfair. This article assesses this objection to the use of QALYs as a basis for allocating health care resources. It seeks to determine what is sound in the double jeopardy objection, and then to show that the defender of QALYs has an adequate response to it.

Attitude to Health↗
PubMed1994

Deformity planning for frontal and sagittal plane corrective osteotomies.

The authors have developed a universal system of geometric deformity planning based on the mechanical or anatomic axes. The place where the axes intersect is the center of rotation angulation (CORA) of a deformity. Osteotomy level and type should be considered relative to the CORA to avoid creating secondary deformities. This type of planning is applicable to both frontal and sagittal plane deformities.

Bone Malalignment↗
PubMed1991

Stereospecific effect of flupenthixol on neuroreceptor gene expression.

An experimental method to test the hypothesis that antipsychotic (neuroleptic) agents influence gene expression in the mouse brain has been developed using the cis and trans stereoisomers of flupenthixol. The cis form of the drug is known to be clinically effective against some of the psychotic symptoms of schizophrenia as opposed to the trans isomer which is relatively inactive. A 2- to 3-fold increase in the abundance of dopamine 2 receptor mRNA was observed in the cis treated mice after a period of ten weeks. No change was observed in the expression of the dopamine D2 receptor gene upon treatment with the trans isomer. No change in the amount of 5-HT1A, 5-HT1C, alpha 1 adrenergic, beta 1 and beta 2 adrenergic neuroreceptor mRNA was found in the mice treated with active drug. The results show a long-term adaptation to D2 antagonism at the level of gene expression which occurs over a similar time scale to that of the clinical response to neuroleptic treatment of schizophrenia.

Actins↗
PubMed1990

Stiffness of the distal tip of bipolar pacing leads.

The stiffness of a bipolar pacing lead, particularly between anode and cathode, may be responsible for myocardial penetration and perforation. Following an unprecedented 7% incidence of high threshold exit block with a single model bipolar ventricular endocardial lead, a study was undertaken to compare pacing lead stiffness between anode and cathode of six models of bipolar leads from two manufacturers; Telectronics (T) and Medtronics (M). Four leads had polyurethane insulation; T 030-284 (Laser Dish), T 329-259 (Cordis, Encor), M 4012 (Target Tip), and M 4004 (Capsure). Two leads had silicone rubber insulation; M 5026 (Capsure) and M 5024 (Capsure SP). All leads were subjected to two stiffness tests. The Tip Deflection Test involved securing the lead at 45 degrees at the indifferent electrode and applying a force to deflect the tip 5 mm. The three point bending test involved placing the lead over two fixed bars in contact with the anode and cathode. Midway a third bar was pushed onto the lead and the force to deflect the lead 2 mm was recorded. The results showed that pacing leads with polyurethane insulation were much stiffer than those with silicone rubber insulation. The T 030-284 because of its construction was found to be the stiffnest. The next stiffnest was the M 4012. Both these leads had an unacceptable incidence of high threshold exit block; 7% with the T 030-284 (89 implants) and 3% with the M 4012 (102 implants). No cases of high threshold exit block were documented with the other four pacing leads and in particular the silicone rubber M 5026 (344 implants).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Pacing, Artificial↗
PubMed1978

[Sensitivity of bacteria to antibiotics. Evaluation of a rapid automatic method (author's transl)].

A rapid automated sensitivity testing system is evaluated in this report. The results have been compared with the standard disk diffusion method (ICS). Three hundred strains recently isolated from clinical cases : Enterobacteriaceae, Staphylococcus aureus, Streptococci D, Pseudomonas aeruginosa, have been tested. The general agreement between the two techniques was 89 p. cent.

Anti-Bacterial Agents↗