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Biomedical subjects

K Farrell

Publications and source records attributed to K Farrell.

At least 19 recordsLinked to original sources
PubMed2001

Current perceived risks of transfusion in the UK and relevance to the future acceptance of blood substitutes.

Data has been gathered on the perception of risk associated with blood donation and transfusion (including the use of so-called blood substitutes) by UK general practitioners (GPs), anaesthetists, healthcare journalists and blood donors of both genders. A questionnaire survey was conducted from March-July 2000 involving (i) GPs (n = 88), (ii) anaesthetists (n = 143), (iii)journalists (n = 20), and (iv) blood donors (n = 250). Respondents rated (scale of 1-7) the general risk of blood transfusion and the risk of infection associated with blood transfusion and donation. Respondents were asked through free response questions to identify the risks they most associated with blood transfusion and the infections associated with blood transfusion and donation. They were also asked to indicate their preference for their own blood, compared to donor blood or a blood substitute and to make a choice between donated blood or a blood substitute. The percentage of respondents who preferred to receive their own blood, compared to donor blood or a suitable substitute, was 73-94%. When required to choose between donor blood or a blood substitute, there were significant (P < 0.05) differences between sample groups: anaesthetists and GPs preferred to receive a blood substitute (52-59%), whereas blood donors and journalists preferred donated blood (74-93%). These findings have clear implications for the future development and implementation of modern transfusion options, including the use and acceptability of blood substitutes as alternatives to donor blood.

Blood Donors↗
PubMed2000

Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter.

We tested the hypothesis that astrocytic glycogen sustains axon function during and enhances axon survival after 60 min of glucose deprivation. Axon function in the rat optic nerve (RON), a CNS white matter tract, was monitored by measuring the area of the stimulus-evoked compound action potential (CAP). Switching to glucose-free artificial CSF (aCSF) had no effect on the CAP area for approximately 30 min, after which the CAP rapidly failed. Exposure to glucose-free aCSF for 60 min caused irreversible injury, which was measured as incomplete recovery of the CAP. Glycogen content of the RON fell to a low stable level 30 min after glucose withdrawal, compatible with rapid use in the absence of glucose. An increase of glycogen content induced by high-glucose pretreatment increased the latency to CAP failure and improved CAP recovery. Conversely, a decrease of glycogen content induced by norepinephrine pretreatment decreased the latency to CAP failure and reduced CAP recovery. To determine whether lactate represented the fuel derived from glycogen and shuttled to axons, we used the lactate transport blockers quercetin, alpha-cyano-4-hydroxycinnamic acid (4-CIN), and p-chloromercuribenzene sulfonic acid (pCMBS). All transport blockers, when applied during glucose withdrawal, decreased latency to CAP failure and decreased CAP recovery. The inhibitors 4-CIN and pCMBS, but not quercetin, blocked lactate uptake by axons. These results indicated that, in the absence of glucose, astrocytic glycogen was broken down to lactate, which was transferred to axons for fuel.

4-Chloromercuribenzenesulfonate↗
PubMed2000

Gas chromatography/negative ion chemical ionization mass spectrometry and liquid chromatography/electrospray ionization tandem mass spectrometry quantitative profiling of N-acetylcysteine conjugates of valproic acid in urine: application in drug metabolism studies in humans.

We report a GC/NICI-MS assay and a LC/ESI-MS/MS assay for the analysis of N-acetylcysteine (NAC) conjugates of (E)-2,4-diene VPA (NAC I and NAC II) identified in humans. The assay also includes the analysis of the NAC conjugate of 4,5-epoxy VPA (NAC III), an identified metabolite in rats treated with 4-ene VPA for its use in metabolic studies in animals. The highly sensitive GC/MS assay was designed to monitor selectively the diagnostic and most abundant [M - 181](-) fragment anion of the di-PFB derivatives of NAC I, NAC II, and NAC IV, the internal standard (IS) and the PFB derivative of NAC III. The higher selectivity of LC/MS/MS methodology was the basis for an assay which could identify and quantitate the underivatized conjugates simultaneously using MRM of the diagnostic ions m/z 130 and 123 arising from the CID of their protonated molecular ions [MH](+). The GC/MS assay employed liquid-liquid extraction whereas the LC/MS/MS assay used a solid-phase extraction procedure. Linearity ranges of the calibration curves were 0.10-5.0microg ml(-1) by GC/MS and 0.10-1.0microg ml(-1) by LC/MS/MS for NAC I, NAC II and NAC III (r(2) = 0.999 or better). Both assays were validated for NAC I and NAC II and provided good inter- and intra-assay precision and accuracy for NAC I and NAC II. The LOQ by LC/MS/MS was 0.1microg ml(-1), representing 1 ng of NAC I and NAC II. The same LOQ (0.1microg ml(-1)) was observed by GC/MS and was equivalent to 100 pg of each metabolite. NAC III was detected at concentrations as low as 0.01 microg ml(-1) by both methods. The total urinary excretion of the NAC conjugates in four patients on VPA therapy was determined to be 0.004-0.088% of a VPA dose by GC/MS and 0.004-0. 109% of a VPA dose by LC/MS/MS.

Acetylcysteine↗
PubMed2000

Factors associated with behavioral and cognitive abnormalities in children receiving topiramate.

The objective of this study was to examine the factors associated with the occurrence of behavioral and cognitive abnormalities in children treated with topiramate. A retrospective chart review of patients up to 18 years of age who had been treated with topiramate at a tertiary epilepsy center was performed. Behavioral or cognitive abnormalities were observed in 11 (14.6%) of 75 children between 2 weeks and 4 months after initiation of therapy. The mean dosage (4.6 mg/kg daily) at which these abnormalities were observed was similar to the mean final dose (5.8 mg/kg daily) in children without abnormalities. The mean rate of dosage increase was 0.72 mg/kg weekly and 0.7 mg/kg weekly in those with and without abnormalities, respectively. Five of the 11 children with behavioral or cognitive abnormalities had a previous history of behavioral or cognitive abnormalities, but only nine of the 64 children without abnormalities had a previous history of behavioral or cognitive abnormalities (P = 0.03). Lamotrigine was used concurrently in four of the 11 children with behavioral or cognitive abnormalities but in only seven of the 64 children without abnormalities (P = 0.05). Behavioral and cognitive abnormalities in children treated with topiramate do not appear to be related to the rate of dosage increase. A previous history of behavioral problems and the concurrent use of lamotrigine may be predisposing factors.

Adolescent↗
PubMed2000

A competency model for general practice: implications for selection, training, and development.

BACKGROUND: The role of the general practitioner (GP) has changed significantly over the past decade. This problem is compounded by growing concern over postgraduate attrition rates from medicine, with current estimates as high as 19%. AIM: To define a comprehensive model of the competencies required for the job role of GP. METHOD: Three independent studies were conducted to define GP competencies including (1) critical incidents focus groups with GPs, (2) behavioural coding of GP-patient consultations, and (3) critical incidents interviews with patients. Study 1 was conducted with GPs (n = 35) from the Trent region. Study 2 involved observation of GP-patient consultations (n = 33 consultations), and Study 3 was conducted with patients (n = 21), all from a Midlands-based medical practice. RESULTS: The data collected from the three studies provided strong evidence for a competency model comprising 11 categories with a summary of the associated behavioural descriptions. Example competencies included empathy and sensitivity, communication skills, clinical knowledge and expertise, conceptual thinking, and coping with pressure. CONCLUSIONS: Triangulation of results was achieved from three independent studies. The competencies derived imply that a greater account of personal attributes needs to be considered in recruitment and training, rather than focusing on academic and clinical competency alone. The model could be employed for future research in design of selection techniques for the role of GP.

Clinical Competence↗
PubMed2000

Identification and characterization of N-acetylcysteine conjugates of valproic acid in humans and animals.

Reactive and hepatotoxic metabolites formed from the biotransformation of valproic acid (VPA) are normally detoxified by conjugating with GSH and followed by mercapturic acid metabolism to produce their respective N-acetylcysteine (NAC) conjugates. Hence, the levels of NAC conjugates of VPA in human urine are an indirect measure of exposure of the liver toward reactive metabolites of the anticonvulsant drug. We report here the synthesis, identification, and characterization of a second NAC conjugate of (E)-2-propyl-2, 4-pentadienoic acid in the urine samples (n = 39) of humans on VPA therapy, namely, (E)-5-(N-acetylcystein-S-yl)-2-ene VPA by gas chromatography/mass spectrometry and liquid chromatography with tandem mass spectrometry. In this study, we were able to separate the diastereomers of (E)-5-(N-acetylcystein-S-yl)-3-ene VPA by HPLC. The NAC conjugate of 4,5-epoxy VPA, namely, 5-NAC-4-OH-VPA gamma-lactone, previously identified in rats treated with 2-propyl-4-pentenoic acid (4-ene VPA), was not detected in any of the human urine samples studied. This suggests that in humans, the P-450 metabolism of 4-ene VPA to the reactive epoxide is not a significant pathway. The excretion of the NAC conjugate of (E)-2, 4-diene VPA glucuronide in the urine of seven patients on VPA was also examined and was not detected. The limit of detection of 5-NAC-3-keto VPA and its decarboxylated product, 1-NAC-3-heptanone, was estimated at 25 ng (signal to noise ratio > 3). Neither 5-NAC-3-keto VPA nor 1-NAC-3-heptanone was detected in the urine of patients on VPA therapy or 4-ene VPA-treated guinea pigs, but 1-NAC-3-heptanone was detected in the urine of 4-ene VPA-treated rats.

Acetylcysteine↗
PubMed1999

K(+)-induced reversal of astrocyte glutamate uptake is limited by compensatory changes in intracellular Na+.

Glutamate uptake is coupled to counter-transport of K+, and high external K+ concentrations can induce reversal of glutamate uptake in whole-cell patch-clamp and isolated membrane preparations. However, high external K+ causes little or no reversal of glutamate uptake in intact astrocytes, suggesting a regulatory mechanism not evident in membrane preparations. One mechanism by which intact cells could limit the effects of altered extracellular ion concentrations on glutamate transport is by compensatory changes in intracellular Na+ concentrations. This possibility was examined using astrocyte cultures treated in two ways to reduce the driving force for glutamate uptake: incubation in high K+ (with reciprocal reduction in Na+), and incubation with metabolic inhibitors to induce ATP depletion. ATP depletion produced a rise in intracellular Na+, a collapse of the membrane sodium gradient and a massive reversal of glutamate uptake. By contrast, incubation in high K+/low Na+ medium did not significantly alter the sodium gradient and did not induce glutamate uptake reversal. The sodium gradient was shown to be maintained under these conditions by compensatory reductions in intracellular Na+ that approximately matched the reductions in extracellular Na+. These findings suggest a mechanism by which astrocytes may limit reversal of glutamate uptake under high K+/low Na+ conditions, and further suggest a general mechanism by which Na(+)-dependent transport processes could be shielded from fluctuating extracellular ion concentrations.

Adenosine Triphosphate↗
PubMed1999

Retrospective study of late febrile seizures.

This retrospective study documents the clinical features, electroencephalographic data, and outcome of 50 children with a history of seizures with fever that occurred after 5 years of age. Children with afebrile seizures before the onset of febrile seizures were excluded. Outcome was based on a cross-sectional survey and the follow-up period was 1-13 years. Of the 50 children, 40 had two or fewer febrile seizures after 5 years of age, and febrile seizures did not occur after 10 years of age. Twenty had complex febrile seizures, and 16 had a first-degree relative with febrile seizures. Five developed afebrile seizures, and 18 had educational difficulties. Epileptiform electroencephalographic abnormalities were observed in 22 but were not predictive of later afebrile seizures. Febrile seizures that occur after 5 years of age recur infrequently and cease by 10 years of age. The risk of developing afebrile seizures in this group is small.

Adolescent↗
PubMed1998

Case-control study of primary human herpesvirus 6 infection in children with febrile seizures.

RATIONALE: Human herpesvirus 6 (HHV-6) has been demonstrated to be the causative agent in roseola infantum. It has been suggested that HHV-6 may have neurotropic properties and be involved in the pathogenesis of febrile seizures in infants. We describe a case-control study to examine the hypothesis that acute HHV-6 infection occurs more commonly in children with febrile seizures than in controls. METHODS: Patients presenting with a first or second febrile seizure between 6 months and 2 years of age were entered in the study. Control patients did not have a seizure but had similar inclusion and exclusion criteria. Specimens were obtained for HHV-6 viral serology and polymerase chain reaction in the acute stage and approximately 2 weeks later. A diagnosis of HHV-6 infection was based on HHV-6-specific IgM and IgG serology and HHV-6 polymerase chain reaction of peripheral blood mononuclear cells and saliva. RESULTS: Eighty-six patients (45 with febrile seizures; 41 controls) were enrolled. The HHV-6 infection status could be determined in only 68 patients (35 with febrile seizures; 33 controls). Acute HHV-6 infection was identified in 15 of 35 febrile seizure patients and in 15 of 33 controls. Evidence of past HHV-6 infection was demonstrated in 13 febrile seizure patients and in 8 controls. CONCLUSIONS: The incidence of primary HHV-6 infection is similar in patients with febrile seizures and age-matched controls. HHV-6 does not seem to be a major factor in the pathogenesis of first and second febrile seizures.

Acute Disease↗