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Biomedical subjects

J Patrick

Publications and source records attributed to J Patrick.

At least 19 recordsLinked to original sources
PubMed2006

Observational assessment of situation awareness, team differences and training implications.

The two goals were to investigate, first, the practicability and reliability of observational assessment of team situation awareness (SA) and, second, the nature of any team differences, their consistency and training implications. Five shift teams tackled three scenarios, each with three probe events concerning SA, and three observers viewed and rated concurrently each shift. This methodology was found to be practicable and achieved satisfactory rater reliability as indicated by intraclass and inter-rater correlations. Team differences in SA emerged although there was no consistent pattern. A retrospective analysis of individual and team behaviours relating to SA was performed using the Critical Incident Technique. A total of 75 incidents and 20 behavioural dimensions relevant to SA were identified and these were subsumed under planning, problem solving, team coordination, attention, communication and knowledge. These findings are discussed with regard to the nature and measurement of SA, and the content of training to improve SA for control room teams.

Adult↗
PubMed2005

Metabolism and excretion of loratadine in male and female mice, rats and monkeys.

The metabolism and excretion of loratadine (LOR), a long-acting non-sedating antihistamine, have been evaluated in male and female mice, rats and monkeys. Following a single (8 mg kg-1) oral administration of [14C]LOR, radioactivity was predominantly eliminated in the faeces. Profiling and characterization of metabolites in plasma, bile, urine and faeces from male and female mice, rats and monkeys showed LOR to be extensively metabolized with quantitative species and gender differences in the observed metabolites. In all species investigated, the primary biotransformation of LOR involved decarboethoxylation to form desloratadine (DL), subsequent oxidation (hydroxylation and N-oxidation) and glucuronidation. More than 50 metabolites were profiled using liquid chromatography-mass spectrometry (LC-MS) with in-line flow scintillation analysis (FSA) and characterized using LC-MSn techniques. The major circulating metabolite in male rats is a DL derivative in which the piperidine ring was aromatized and oxidized to pyridine-N-oxide. Much lower levels of the pyridine-N-oxide metabolite were observed in female rat plasma. In contrast, the relative amount of DL was notably higher in female than in male rats. The major circulating metabolite in either gender of mouse and male monkey is a glucuronide conjugate of an aliphatic hydroxylated LOR; in the female monkey, the major circulating metabolite is formed through oxidation of the pyridine moiety and subsequent glucuronidation. Qualitatively similar metabolic profiles were observed in the mouse, rat and monkey urine and bile, and the metabolites characterized resulted from biotransformation of LOR to DL, hydroxylation of DL and subsequent glucuronide conjugation. 5-Hydroxy-desloratadine was the major faecal metabolite across all three species irrespective of gender.

Animals↗
PubMed2004

Disposition and pharmacokinetics of temozolomide in rat.

1. Temozolomide, an imidazotetrazine derivative, is a cytotoxic alkylating agent of broad-spectrum antitumour activity. The absorption, metabolism, distribution and excretion of temozolomide have been investigated in male and female Sprague-Dawley and Long-Evans rats following single oral or intravenous dose administration of 200 mg m(-2) non-radiolabelled or (14)C-radiolabelled temozolomide. The distribution of (14)C-temozolomide was also evaluated by whole-body autoradiography in male Sprague-Dawley rats. Plasma concentrations of temozolomide and its active metabolite 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) were determined by high-performance liquid chromatography (HPLC) with ultraviolet detection. Plasma, urine and faeces were profiled by HPLC with radiochemical detection. 2. Temozolomide was rapidly and extensively (>90%) absorbed and widely distributed in tissues. The distribution pattern of radioactivity was gender independent. Penetration into the brain following oral or intravenous administration was 35-39% based on the brain/plasma AUC ratio. 3. Following intravenous or oral administration, temozolomide was primarily eliminated renally (75-85% of the dose) as either unchanged drug, a carboxylic acid analogue, AIC (a degradation product) and a highly polar unidentified peak. Biliary excretion was minimal (1.4-1.6%). The pharmacokinetics (oral versus intravenous) were similar and gender independent. The absolute oral availability was 96-100%. Temozolomide was rapidly eliminated (t(1/2) = 1.2 h) and converted to MTIC. 4. Systemic exposure to MTIC was about 2% that of temozolomide. Overall, the disposition of temozolomide in rats was similar to that observed in humans.

Administration, Oral↗
PubMed2001

Development of functional electrical stimulators utilizing cochlear implant technology.

In 1983, R. Davis proposed the development of a functional electrical stimulator, based on multi-channel cochlear implant technology, for the restoration of function in spinal cord injured paraplegic subjects. In 1984, the US Veteran Administration funded the initial investigations including animal experiments and purchase of a FES stimulator based on the Nucleus 22 cochlear implant. In 1987, the US Food and Drug Administration approved an Investigational Device Exemption (IDE# G870142) for this FES project. In 1991, the first stimulator was implanted in a 21-year old male paraplegic subject (complete thoracic spinal cord lesion at level #10), who was subsequently able to stand and to perform one-handed tasks for up to 1h. In 1996-1997 development started on a new multi-function FES system. In 1998, a stimulator was implanted in a 35-year-old male paraplegic subject (complete thoracic spinal cord lesion at level #10). After 8 months of use providing multiple functions including bladder voiding, the implant's internal antenna wire broke. A modified implant (FES 24-B) is due to be implanted in July 2001.

Adult↗
PubMed2001

The plasma concentration and LDL-C relationship in patients receiving ezetimibe.

Ezetimibe is a novel selective inhibitor of intestinal cholesterol absorption, which has been shown to significantly decrease low-density lipoprotein cholesterol (LDL-C). In this article, the relationship between plasma ezetimibe concentrations and lowering of LDL-C is determined using Emax and regression models. Data from two phase II double-blind placebo-controlled studies (n = 232 and 177) were used in which daily doses of ezetimibe ranging from 0.25 to 10 mg were administered for 12 weeks. Ezetimibe concentrations correlated significantly with percentage change in LDL-C from baseline (%LDL-C). Reductions in %LDL-C of 10%, 15%, and 20% were achieved with concentrations in the ranges 0 to 2, 2 to 15, and > 15 ng/ml, respectively, as compared with placebo. To achieve > 15% reduction in LDL-C, patients need to maintain trough concentrations > 15 ng/ml, taking plasma concentrations as a surrogate for concentrations at the enterocyte. Based on the doses administered, the 10 mg dose had the highest likelihood of sustaining such concentrations, confirming that a daily 10 mg dose of ezetimibe is an optimal therapeutic dose in the treatment of hypercholesterolemia.

Adolescent↗
PubMed2000

Liquid chromatography/mass spectrometry methods for distinguishing N-oxides from hydroxylated compounds

This study describes the application of liquid chromatography/mass spectrometry (LC/MS) methods for distinguishing between aliphatic and aromatic hydroxylations and between hydroxylations and N-oxidations. Hydroxylations and N-oxidations are common biotransformation reactions of drugs. Electrospray (ESI) and atmospheric pressure chemical ionization (APCI) were used to generate ions from liquid chromatographic effluents. ESI-MS, ESI-MS/MS, APCI-MS, and APCI-MS/MS experiments were performed on several metabolites and derivatives of loratadine (a long-acting and nonsedating tricyclic antihistamine) using an ion trap mass spectrometer (LCQ) and a triple-quadrupole mass spectrometer (TSQ). The observations are as follows: (1) LC/ESI-MS produced predominantly [M + H]+ ions with minor fragmentation. (2) LC/ESI-MS/MS data, however, showed a predominant loss of water from metabolites with aliphatic hydroxylation while the loss of water was not favored when hydroxylation was phenolic. N-Oxides (aromatic and aliphatic) showed only a small amount of water loss in the MS/MS spectra. (3) Under LC/APCI-MS conditions, aliphatic hydroxylation could be readily distinguished from aromatic hydroxylation based on the extent of water loss. In addition, N-oxides produced distinct [M + H - O]+ ions. These [M + H - O]+ ions were not produced in the APCI-MS spectra of hydroxylated metabolites. (4) Similar to the ESI-MS/MS spectra, the APCI-MS/MS spectra from the (M + H)+ ions of N-oxides yielded a small amount of water loss but no [M + H - O]+ ions. These results indicate that LC/APCI-MS can be used to distinguish between hydroxylated metabolites and N-oxides.

Journal Article↗
PubMed2000

Tilt testing for syncope.

Vasovagal syncope is a common cause of sudden collapse. It results from inappropriate activation of left ventricular mechanoreceptors causing sudden vasodilation with bradycardia. Tilt testing is an inexpensive and non-invasive way of establishing a vasovagal diagnosis in unexplained syncope. If critical care nurses improve their understanding of the pathophysiology of vasovagal syncope and the procedure of tilt testing, their care of syncopal patients will be enhanced. This literature review discusses the pathophysiology and clinical presentation of vasovagal syncope. The procedure of tilt testing is explained and the treatment of vasovagal syncope is briefly reviewed.

Critical Care↗
PubMed1999

Megacystis, mydriasis, and ion channel defect in mice lacking the alpha3 neuronal nicotinic acetylcholine receptor.

The alpha3 subunit of the neuronal nicotinic acetylcholine receptor is widely expressed in autonomic ganglia and in some parts of the brain. The alpha3 subunit can form heteromultimeric ion channels with other alpha subunits and with beta2 and beta4 subunits, but its function in vivo is poorly understood. We prepared a null mutation for the alpha3 gene by deletion of exon 5 and found that homozygous (-/-) mice lacked detectable mRNA on Northern blotting. The -/- mice survive to birth but have impaired growth and increased mortality before and after weaning. The -/- mice have extreme bladder enlargement, dribbling urination, bladder infection, urinary stones, and widely dilated ocular pupils that do not contract in response to light. Detailed histological studies of -/- mice revealed no significant abnormalities in brain or peripheral tissues except urinary bladder, where inflammation was prominent. Ganglion cells and axons were present in bladder and bowel. Bladder strips from -/- mice failed to contract in response to 0.1 mM nicotine, but did contract in response to electrical field stimulation or carbamoylcholine. The number of acetylcholine-activated single-channel currents was severely reduced in the neurons of superior cervical ganglia in -/- mice with five physiologically distinguishable nicotinic acetylcholine receptor subtypes with different conductance and kinetic properties in wild-type mice, all of which were reduced in -/- mice. The findings in the alpha3-null mice suggest that this subunit is an essential component of the nicotinic receptors mediating normal function of the autonomic nervous system. The phenotype in -/- mice may be similar to the rare human genetic disorder of megacystis-microcolon-intestinal hypoperistalsis syndrome.

Animals↗
PubMed1999

Screening for Down's syndrome: experience of two district general hospitals having different screening strategies.

The aim of this retrospective study is to determine the rate of reduction in the number of Down's syndrome babies delivered in two hospitals having different screening strategies. The total number of Down's syndrome babies during the study period was 0.6/1000 births at Birch Hill Hospital and 1.9/1000 births at Oldham Hospital. Antenatal diagnosis of Down's syndrome was made in 1/4 of women (25%) at Birch Hill and 7/19 of women (37%) in Oldham. The reduction rate of Down's syndrome was similar in both hospitals (25 and 26%). This retrospective analysis and comparison between two neighbouring units, highlights the fact that there is little standardisation of screening policies and screening programmes have not resulted in a substantial reduction in Down's syndrome babies.

Journal Article↗
PubMed1998

A study of the effect of cyproheptadine on gait in hemiplegic children.

The properties of cyproheptadine as an anti-spastic agent have been reported since 1980. In this study we sought to investigate whether gait function, as specified by stride length, cadence, heart rate, and also by questionnaire, correlated with cyproheptadine medication during a double-blind matched-placebo cross-over trial, undertaken on a group of 16 hemiplegic spastic patients aged 4-18 years. We found that neither qualitative nor quantitative analyses suggested any systematic change in gait parameters dependent on cyproheptadine medication. We conclude that our study on 16 patients showed no statistical evidence of improvement in spasticity due to the action of cyproheptadine. An effect was, however, found in the case of mean patient heart rate, which was 10% higher (P<0.003) at the end of the cyproheptadine medication period. Copyright 1998 Elsevier Science B.V.

Journal Article↗
PubMed1997

Peptidyl prolyl cis-trans isomerase activity of cyclophilin A in functional homo-oligomeric receptor expression.

The functional expression of homo-oligomeric alpha7 neuronal nicotinic and type 3 serotonin receptors is dependent on the activity of a cyclophilin. In this paper we demonstrate that the mechanism of cyclophilin action during functional homo-oligomeric receptor expression in Xenopus oocytes is distinct from the calcineurin-dependent immunosuppressive mechanism by showing that a nonimmunosuppressive analog of cyclosporin A (CsA), SDZ 211-811, reduces functional receptor expression to the same extent as CsA. The cytoplasmic subtype of cyclophilin, cyclophilin A (CyPA), appears to be required for functional receptor expression. This is because overexpression of CyPA and a CyPA mutant that is deficient in CsA binding activity reverses CsA-induced reduction in functional receptor expression. The mechanism of action of CyPA is likely to involve its prolyl isomerase activity because a mutant CyPA with a single amino acid substitution (arginine 55 to alanine) that is predicted to produce a 1000-fold attenuation in isomerase activity fails to reverse the cyclosporin A effect. Our data also suggest that CyPA does not form a stable complex with receptor subunits.

Amino Acid Isomerases↗
PubMed1997

Paraplegia: prolonged closed-loop standing with implanted nucleus FES-22 stimulator and Andrews' foot-ankle orthosis.

Our object is to develop a reliable, implantable and closed-loop functional electrical stimulator (FES) hybrid system for safe prolonged standing in paraplegic individuals. Open-loop FES systems rapidly induce muscle fatigue that limits paraplegic standing to less than 20 and typically 10 min. Since December 1991, a paraplegic male (CS: 23 years old, T10 level, Asia: A) has been implanted with the first Nucleus FES-22 channel stimulating system (Cochlear Ltd., Lane Cove, N.S.W., Australia). Epineural platinum disc electrodes (2.5 mm) were placed on branches of the femoral, gluteal and sciatic nerves, which can be activated to produce controlled lower extremity movements for exercise and standing. No medical complications have occurred during these 5 1/2 years of implantation. The ankles are stabilized with Andrews' ankle-foot braces, the knees are free to flex. With bilateral knee goniometers fitted to sense a 10 degrees angle flexion, this hybrid closed-loop stimulation system allows the patient to achieve safe uninterrupted standing for over 60 min. The stimulator has needed to be activated 'on' for 8% (range: 3-17%) of the standing times, preventing muscle fatigue, with little or no changes found in the vital signs. The patient can manipulate and transfer objects at arm length up to 2.2 kg with good stability. New, less obstrusive sensors are currently being tested for a safer and more reliable closed-loop system.

Adult↗
PubMed1996

Impulsivity, defensive functioning, and borderline personality disorder.

OBJECTIVE: To replicate previous research suggesting that impulsivity highly predicts current DIB(R) score and social functioning, with the additional inclusion of other measures, including defensive functioning. METHOD: Correlational analyses between impulsivity and other measures, and regression analyses with DIB(R) and SAS-SR as outcome measures, and impulsivity and other measures as predictor variables, were performed on data derived from n = 57 initially borderline personality disorder (BPD) subjects recruited as part of a 7-year follow-up study of BPD. RESULTS: Data showed strong correlations between the elements of impulsivity described previously and defensive functioning. The initial study results were repeated, and only a minor contribution from defensive functioning additionally contributed to the regression models. No other variables entered the model, unless anger was dropped from the variables entered into the analysis. CONCLUSIONS: The results may contribute to a better definition of the term "impulsivity" as related to BPD, and may lead to further, improved research into the cause, treatment, and prognosis of BPD.

Borderline Personality Disorder↗
PubMed1996

A controlled trial of general practitioners' attitudes to patients with schizophrenia.

OBJECTIVE: To examine general practitioners' attitudes to patients with schizophrenia. DESIGN: A random sample of primary care physicians were alternately sent a case vignette of a patient with or without schizophrenia, in an otherwise identical clinical abstract, and asked to indicate their level of agreement with fifteen statements based on it. SUBJECTS AND SETTING: A one-in-five sample of general practitioners who were identified from the Primary Care Services Register of Lothian Health Board. RESULTS: The median score for each statement was compared by the two-tailed Wilcoxon rank sum test. Doctors responding to the vignette of the patient with schizophrenia were significantly less willing to have the patient on their practice list, more likely to refer them to a specialist and more likely to think that they would be violent; whereas they did not think that they would take up any more time than the other patient. These impressions were no different between those who had or had not received work training in psychiatry. CONCLUSIONS: This controlled trial of primary care physicians' attitudes towards patients with schizophrenia amounts to an empirical demonstration of medical discrimination against the sufferers of this and potentially of other long term psychiatric disorders. Psychiatrists and general practitioners should share care in the management of schizophrenia and try to overcome the prejudices against such patients in an attempt to improve their overall clinical care.

Attitude of Health Personnel↗