Biomedical subjects

M Lee

Publications and source records attributed to M Lee.

At least 73 records · Page 4Linked to original sources

PubMed2003

Cerebral autoregulation in children during sevoflurane anaesthesia.

INTRODUCTION: Little is known about cerebral autoregulation in children. The aim of this study was to examine cerebral autoregulation in children. METHODS: Cerebral autoregulation testing was performed during less than 1 MAC sevoflurane anaesthesia in children (from 6 months to 14 yr) and in adults (18-41 yr). Mean middle cerebral artery flow velocities (V(MCA)) were measured using transcranial Doppler ultrasonography. Mean arterial pressure (MAP) was increased to whichever was greater: 20% above baseline or (i) 80 mm Hg for less than 9 yr, (ii) 90 mm Hg for 9-14 yr, and (iii) 100 mm Hg for adults. Cerebral autoregulation was considered intact if the autoregulatory index was > or =0.4. RESULTS: There were 13 subjects less than 2 yr old (Group 1), 13 subjects 2-5 yr (Group II), 14 subjects 6-9 yr (Group III), 12 subjects 10-14 yr (Group IV), and 12 adults (Group V; control group). All subjects had an autoregulatory index > or =0.4. There was no difference in autoregulatory index between children in Groups I-IV or between children and adults. DISCUSSION: We found no age-related differences in autoregulatory capacity during low-dose sevoflurane anaesthesia. We report no differences in autoregulatory capacity between children and adults.

Adolescent↗

PubMed2003

High-level beta-lactam resistance associated with acquired multidrug resistance in Helicobacter pylori.

Four clinical Helicobacter pylori isolates with high-level resistance to beta-lactams exhibited low- to moderate-level resistance to the structurally and functionally unrelated antibiotics ciprofloxacin, chloramphenicol, metronidazole, rifampin, and tetracycline. This pattern of multidrug resistance was transferable to susceptible H. pylori by natural transformation using naked genomic DNA from a clinical multidrug-resistant isolate. Acquisition of the multidrug resistance was also associated with a change in the genotype of the transformed multidrug-resistant H. pylori. DNA sequence analyses of the gene encoding penicillin binding protein 1A (PBP 1A) showed 36 nucleotide substitutions resulting in 10 amino acid changes in the C-terminal portion (the putative penicillin binding domain). Acquisition of beta-lactam resistance was consistently associated with transfer of a mosaic block containing the C-terminal portion of PBP 1A. No changes of genes gyrA, rpoB, rrn16S, rdxA, and frxA, and nine other genes (ftsI, hcpA, llm, lytB, mreB, mreC, pbp2, pbp4, and rodA1) encoding putative PBPs or involved in cell wall synthesis were found among the transformed resistant H. pylori. Antibiotic accumulations of chloramphenicol, penicillin, and tetracycline were all significantly decreased in the natural and transformed resistant H. pylori compared to what was seen with susceptible H. pylori. Natural transformation also resulted in the outer membrane protein profiles of the transformed resistant H. pylori becoming similar to that of the clinical resistant H. pylori isolates. Overall, these results demonstrate that high-level beta-lactam resistance associated with acquired multidrug resistance in clinical H. pylori is mediated by combination strategies including alterations of PBP 1A and decreased membrane permeability.

Amino Acid Sequence↗

PubMed2003

Drowning your sorrows? Attitudes towards alcohol in UK Jews and Protestants: a thematic analysis.

BACKGROUND: Jewish culturally supported beliefs may discourage drinking and drunkenness as ways of socialising and coping with stress. Thus Jewish men under stress may be relatively more likely to become depressed, and less likely to use and abuse alcohol. This study is the first qualitative comparison of Jews and Protestants, men and women. It examines whether alcohol-related beliefs are consistent with the alcohol-depression hypothesis, i.e. that positive beliefs about alcohol use and effects are associated with high alcohol use and low depression. MATERIAL AND DISCUSSION: A thematic (interpretive phenomenological) analysis on open-ended question responses, from 70 Jews and 91 Protestants, and on semi-structured interviews with five Jews and four Protestants, identified three salient themes: the importance of retaining self-control; the pleasures of losing inhibitions; and the relations of alcohol-related behaviour to identity. Compared to Protestants, Jews described alcohol-related behaviour as threatening to self-control, loss of inhibition as unenjoyable and dangerous and distinguished between the kinds of drinking behaviours appropriate for Jews and others. Sub-themes for Protestant men were denial that drinking threatens self-control, and appropriateness of going to the pub. CONCLUSIONS: The themes identified are not measurable using published research instruments. Alcohol-related behaviour may be a feature of Jewish identity. The beliefs identified are consistent with the alcohol-depression hypothesis.

Adult↗

PubMed2002

Observations of comet 19P/Borrelly by the miniature integrated camera and spectrometer aboard Deep Space 1.

The nucleus of the Jupiter-family comet 19P/Borrelly was closely observed by the Miniature Integrated Camera and Spectrometer aboard the Deep Space 1 spacecraft on 22 September 2001. The 8-kilometer-long body is highly variegated on a scale of 200 meters, exhibiting large albedo variations (0.01 to 0.03) and complex geologic relationships. Short-wavelength infrared spectra (1.3 to 2.6 micrometers) show a slope toward the red and a hot, dry surface (</=345 kelvin, with no trace of water ice or hydrated minerals), consistent with approximately 10% or less of the surface actively sublimating. Borrelly's coma exhibits two types of dust features: fans and highly collimated jets. At encounter, the near-nucleus coma was dominated by a prominent dust jet that resolved into at least three smaller jets emanating from a broad basin in the middle of the nucleus. Because the major dust jet remained fixed in orientation, it is evidently aligned near the rotation axis of the nucleus.

Carbon↗

PubMed2002

Band-gap tuning and linear magnetoresistance in the silver chalcogenides.

Optimally doped silver selenide and silver telluride exhibit linear positive magnetoresistance over decades in magnetic field and on a scale comparable to the colossal magnetoresistance compounds. We use hydrostatic pressure to smoothly alter the band structure of Ag-rich and Ag-deficient samples of semiconducting Ag(2 +/-delta)Te of fixed stoichiometry and disorder. We find that the magnetoresistance spikes and the linear field dependence emerges when the bands cross and the Hall coefficient changes sign.

Journal Article↗

PubMed2002

Checkerboard DNA-DNA hybridisation technology focused on the analysis of Gram-positive cariogenic bacteria.

Checkerboard DNA-DNA hybridisation enabled the quantitative analysis of plaque samples against 40 microbial species simultaneously, using digoxygenin-labelled, whole-genome DNA probes. This technique was initially developed to study the predominantly Gram-negative sub-gingival plaque microbiota. The aim of this study was to apply it to a suite of predominantly Gram-positive microorganisms, such as those implicated in cariogenesis. To specifically target Gram-positive species (and Candida albicans) required optimisation and modification of DNA extraction, prehybridisation, hybridisation, and antibody detection conditions. The suitability of the revised technique for clinical and epidemiological studies was confirmed using interproximal plaque from small groups of 5- to 6-year-old children of high (decayed, missing, or filled teeth (dmft)> or =5, n=8) and zero (n=5) caries rates.

Buffers↗

PubMed2002

Ultrasonic spectral parameter characterization of apoptosis.

Ultrasound (US) spectral analysis methods are used to analyze the radiofrequency (RF) data collected from cell pellets exposed to chemotherapeutics that induce apoptosis and other chemicals that induce nuclear transformations. Calibrated backscatter spectra from regions-of-interest (ROI) were analyzed using linear regression techniques to calculate the spectral slope and midband fit. Two f/2 transducers, with operating frequencies of 30 and 34 MHz (relative bandwidths of 93% and 78%, respectively) were used with a custom-made imaging system that enabled the collection of the raw RF data. For apoptotic cells, the spectral slope increased from 0.37 dB/MHz before drug exposure to 0.57 dB/MHz 24 h after, corresponding to a change in effective scatterer radius from 8.7 to 3.2 microm. The midband fit increased in a time-dependent fashion, peaking at 13dB 24 h after exposure. The statistical deviation of the spectral parameters was in close agreement with theoretical predictions. The results provide a framework for using spectral parameter methods to monitor apoptosis in in vitro and in in vivo systems and are being used to guide the design of system and signal analysis parameters.

Apoptosis↗

PubMed2002

VNS therapy in clinical practice in children with refractory epilepsy.

OBJECTIVES: To study the efficacy, tolerability and safety of the vagus nerve stimulation (VNS) therapy in clinical practice, in 16 children and adolescents with refractory epilepsy. METHODOLOGY: We assessed the efficacy of VNS therapy, retrospectively by comparing seizure frequency, duration and severity at the time of most recent follow up (av: 24.9 months) to that in the 4 weeks prior to VNS surgery. Changes in quality of life, sleep and behaviour at last review was compared with that prior to VNS. Adverse effects elicited by specific questioning, spontaneous reporting and clinical examination are described. RESULTS: Vagus nerve stimulation resulted in a >50% reduction in seizure frequency in 62.5% of children with 25% achieving a >90% reduction. Vagus nerve stimulation was well tolerated in all but one of our cohort, with no serious side-effects. CONCLUSION: Our results support its role as one of the options in intractable childhood epilepsy.

Adolescent↗

PubMed2002

Dopamine depletion results in increased neostriatal D(2), but not D(1), receptor binding in humans.

The effect of endogenous dopamine (DA) on neostriatal DA D(1) and D(2) receptor binding potentials (D(1)RBP and D(2)RBP, respectively) in vivo was evaluated with positron emission tomography (PET) and the radiotracers [(11)C]SCH23390 and [(11)C]raclopride, respectively, by comparing the D(1)RBP and D(2)RBP before and after acute DA depletion. DA depletion was achieved by per-oral administration of 4500 mg alpha-methyl-para-tyrosine (AMPT) given in the 25 h prior to [(11)C]SCH23390 PET and of 5250 mg AMPT given in the 29 h prior to [(11)C]raclopride PET. Six healthy subjects completed the protocol. The AMPT treatment decreased plasma levels of the DA metabolite homovanillic acid by 61 +/- 16% (4500 mg; average +/- standard deviation) and 62 +/- 17% (5250 mg), and levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol by 58 +/- 7% (4500 mg) and 66 +/- 5% (5250 mg). This AMPT treatment increased D(2)RBP significantly from 3.18 +/- 0.34 to 3.59 +/- 0.30 but no significant change was observed in D(1)RBP (1.64 +/- 0.24 pre AMPT vs 1.70 +/- 0.17 post AMPT). Thus, while DA depletion "uncovers" D(2)receptors, it does not do so for D(1) receptors. The implications of this finding for measuring endogenous DA and its effects on in vivo receptor binding in humans are discussed.

Administration, Oral↗

PubMed2002

Properties of neurotoxic peptides related to the BRI gene.

Mutations in the BRI gene are thought to cause dementias in members of families. The clinical symptoms are similar to those of Alzheimer's disease, but with additional ocular and hearing deficits, and spasticity. The mutations lead to the release of the 34-residue peptides, ABri and ADan, in the brains of afflicted individuals. We have synthesized the peptides in their straight-chain and oxidized cyclic forms and shown that the oxidized form of ABri and reduced form of ADan are toxic to human neuronal cell lines in culture. Neurotoxicity correlates with the extent of formation of SDS-stable non-fibrillar low-molecular-mass oligomers (SSNFOs).

Adaptor Proteins, Signal Transducing↗

PubMed2002

Tolerance for depression: are there cultural and gender differences?

This study examined tolerance for depression among Jewish and Protestant men and women in the United Kingdom. A measure of tolerance for depression was developed, which examined willingness to admit to and seek help for depression. More specifically, the items in the measure (developed from extended interviews) covered empathy towards sufferers, potential virtues of the illness, hopes for treatment, seeing the illness as 'normal', and telling other people about it. Existing evidence suggested that tolerance for depression might be greater amongst Jews compared with Protestants, and women compared with men. Also, Jewish men were expected to be more tolerant than Protestant men, whereas Protestant and Jewish women were not expected to differ from each other. It was found that tolerance for depression was greater amongst Jews than Protestants, and this is consistent with the elevated levels of depression amongst Jewish men as compared with Protestant men. However, findings relating to gender were mixed and were not always consistent with our expectations. The findings suggest that there may be some cultural variations in willingness to admit to and seek help for depression, and this may be worth examining in other cultural-religious groups. Individual variations in tolerance for depression may be clinically significant.

Adolescent↗

PubMed2002

Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis.

Intravenous immunoglobulin (IVIG) has several effects on the immune system that could have a beneficial influence on disease processes in multiple sclerosis (MS). Four double-blind trials in relapsing-remitting MS have demonstrated that IVIG may reduce the relapse rate, progression and the number of gadolinium-enhancing lesions. However, these trials were smaller than the pivotal trials of interferon-beta and glatiramer acetate, and therefore, we performed a meta-analysis of the four trials in order to provide an overall assessment of the benefits of IVIG in relapsing-remitting multiple sclerosis in comparison with other drugs currently available for treatment of disease activity in MS. The meta-analysis showed a significant beneficial effect on the annual relapse rate (effect size -0.5; P = 0.00003), on the proportion of relapse-free patients (0.29 difference; P = 2.1 x 10(-8)), change in Expanded Disability Status Scale (EDSS) score (effect size: 0.25; P = 0.04), and a trend towards a reduction in the proportion of patients who deteriorated (P = 0.03). Each single study in the meta-analysis had its weaknesses, but all studies were positive regarding their primary end-point, and the results yield concordant evidence for reduction of relapse rate and progression. The ideal dosage of IVIG for treating MS needs still to be determined. In conclusion, IVIG may be a valuable alternative for treatment of relapsing-remitting MS, but can presently not be considered as a first-line treatment. IVIG could be considered in patients who do not tolerate or are unwilling to take the approved injectable medications, but additional studies are needed to establish the role of IVIG in the management of multiple sclerosis.

Persons with Disabilities↗

PubMed2002

Manual examination of accessory movements--seeking R1.

Movement diagrams are used by physiotherapists to depict the behaviour of resistance through the available range of accessory and physiological joint movement. It is generally accepted that for an asymptomatic joint, the resistance first felt by the therapist (R1) occurs towards the end of range. R1 is considered to be at the transition point between the toe and linear region of a load displacement curve. The aim of this study was to more accurately define R1 from force displacement curves of accessory movement to the spine and peripheral joints using a validated instrument, the Spinal Assessment Machine (SAM). Thirty archived force displacement curves obtained using the SAM, which applied a posteroanterior force of 100N at a frequency of 0.5 Hz to L3 spinous process, were examined. In addition force displacement curves were similarly obtained from the tibiofemoral joint, glenohumeral joint and radiocarpal joint of one asymptomatic individual. In all cases resistance to a PA movement commenced at the beginning of range, the curve ascending as soon as the force was applied. While in most cases there was a low stiffness 'toe' region there was no unambiguous point where it could be said that the toe region ended. It is concluded that for spinal and peripheral accessory movements both the onset of resistance and the toe occurs at the beginning of range. Therapists should therefore depict R1 at the beginning of range not toward the end of range as is current practice.

Humans↗

PubMed2002

The response of posteroanterior lumbar stiffness to repeated loading.

Lumbar posteroanterior (PA) responses are determined by manual examination and are used to guide treatment decisions and interpret changes in symptoms within and between treatments. Mechanical devices that simulate manual assessment have been developed to measure lumbar PA responses. The two variables used to describe lumbar PA responses to mechanical loading are stiffness coefficient K and displacement D30. The purpose of this study was to investigate the behaviour of lumbar PA responses with repeated loading over time. Lumbar PA responses at L4 were measured in 18 pain-free subjects using a mechanical device. Measurements were made for five consecutive loading cycles on three test occasions. The responses were compared between the five cycles within a single test occasion and between three test occasions. An identical procedure was also used to test a set of elastic springs for comparison. There was a significant increase in both stiffness coefficient K and displacement D30 between the first cycle and subsequent cycles of a single test occasion on human subjects. This response which demonstrates an increase in stiffness and displacement between the first and subsequent cycles can be considered a normal response to PA loading. PA stiffness remains constant over several tests both within one day and between days.

Adult↗

PubMed2002

Why study pain? A qualitative analysis of medical and nursing faculty and students' knowledge of and attitudes to cancer pain management.

Although effective means for pain management have long been available, cancer pain remains widely undertreated. Surveys of medical personnel have revealed knowledge deficits and attitudinal barriers to pain management, but have not determined why such attitudes persist and how they may be addressed in medical and nursing curricula. This paper presents findings from a qualitative study of the beliefs and attitudes toward pain and cancer pain management held by medical and nursing students and faculty who participated in the Cancer Education Module for the Management of Pain (CEMMP) project. Analysis centered on informants' prioritization and knowledge of pain and cancer pain management and on the meanings informants assigned to pain in a clinical context. Themes in prioritization included the importance of learning about pain versus cancer pain and the responsibility of primary care providers versus specialists for pain and cancer pain management. Themes in informants' knowledge of pain included knowledge deficits about medications and adjunct therapies and the presence of pain management in the curriculum, and the role of knowledgeable faculty members and mentors in the dissemination of information about pain management. Themes in the meanings informants' assigned to pain included opioidphobia, and the (inter-)subjectivity of pain. The discussion focuses in particular on tensions within the prioritization, knowledge and meanings of pain that must be resolved before students can be appropriately educated for optimal pain management.

Attitude of Health Personnel↗

PubMed2002

Nicotinic receptor abnormalities in the cerebellar cortex in autism.

Autism is a common developmental disorder associated with structural and inferred neurochemical abnormalities of the brain. Cerebellar abnormalities frequently have been identified, based on neuroimaging or neuropathology. Recently, the cholinergic neurotransmitter system has been implicated on the basis of nicotinic receptor loss in the cerebral cortex. Cerebellar cholinergic activities were therefore investigated in autopsy tissue from a series of autistic individuals. The presynaptic cholinergic enzyme, choline acetyltransferase, together with nicotinic and muscarinic receptor subtypes were compared in the cerebellum from age-matched mentally retarded autistic (eight), normal control (10) and non-autistic mentally retarded individuals (11). The nicotinic receptor binding the agonist epibatidine (the high affinity receptor subtype, consisting primarily of alpha3 and alpha4, together with beta2 receptor subunits) was significantly reduced by 40-50% in the granule cell, Purkinje and molecular layers in the autistic compared with the normal group (P < 0.05). There was an opposite increase (3-fold) in the nicotinic receptor binding alpha-bungarotoxin (to the alpha7 subunit) which reached significance in the granule cell layer (P < 0.05). These receptor changes were paralleled by a significant reduction (P < 0.05) and non-significant increase, respectively, of alpha4 and alpha7 receptor subunit immunoreactivity measured using western blotting. Immunohistochemically loss of alpha(4 )reactivity was apparent from Purkinje and the other cell layers, with increased alpha7 reactivity in the granule cell layer. There were no significant changes in choline acetyltransferase activity, or in muscarinic M1 and M2 receptor subtypes in autism. In the non-autistic mentally retarded group, the only significant abnormality was a reduction in epibatidine binding in the granule cell and Purkinje layers. In two autistic cases examined histologically, Purkinje cell loss was observed in multiple lobules throughout the vermis and hemispheres. This was more severe in one case with epilepsy, which also showed vermis folial malformation. The case with less severe Purkinje cell loss also showed cerebellar white matter thinning and demyelination. These findings indicate a loss of the cerebellar nicotinic alpha4 receptor subunit in autism which may relate to the loss of Purkinje cells, and a compensatory increase in the alpha7 subunit. It remains to be determined how these receptor abnormalities are involved in neurodevelopment in autism and what is the relationship to mental function. Since nicotinic receptor agonists enhance attentional function and also induce an elevation in the high affinity receptor, nicotinic therapy in autism may be worth considering.

Adult↗

PubMed2002

Brain SPECT: a controlled, blinded assessment of intra-reader and inter-reader agreement.

A detailed assessment of intra- and inter-reader variation in the interpretation of brain SPECT scans has been performed. A random sample was selected from scans performed at a community/teaching hospital in Seattle. Scans were interpreted independently by three experienced readers who were blinded to all patient information. Forty-eight scans were interpreted twice by each reader, for a total of 288 readings. Readers recorded detailed assessments of individual lesions and overall impressions using a standardized reporting form. Intra-observer agreement as reflected in per cent agreement for severity scores ranged from 65% to 100%. Intra-observer agreement on the 'overall impression' was very good for Alzheimer's pattern (kappa=0.73-1.00), and fair to good for the 'heterogeneous pattern' (kappa=0.30-0.63). Inter-observer agreement, as reflected in per cent agreement, ranged from 29% to 100%. Inter-observer agreement about the 'overall impression' was fair to moderate for Alzheimer's pattern (kappa=0.24-0.54) and was poor for the descriptors 'heterogeneous' and 'normal'. It is concluded that brain SPECT has great potential value in many important conditions. This study demonstrates a need for further work in the areas of pattern definition and reduction of observer variation.

Adult↗

PubMed2002

mSprouty2 inhibits FGF10-activated MAP kinase by differentially binding to upstream target proteins.

Murine Sprouty2 (mSpry2) is a conserved ortholog of Drosophila Sprouty, a gene that inhibits several tyrosine kinase receptor pathways, resulting in net reduction of mitogen-activated protein (MAP) kinase activation. However, the precise mechanism mediating mSpry2 function as a negative regulator in tyrosine kinase growth factor pathways that regulate diverse biological functions remains incompletely characterized. Fibroblast growth factor 10 (FGF10) is a key positive regulator of lung branching morphogenesis and induces epithelial expression of mSpry2 adjacent to mesenchymal sites of FGF10. Herein, we demonstrate that FGF10 stimulation of mouse lung epithelial cells (MLE15) overexpressing mSpry2 results in both mSpry2 tyrosine phosphorylation and differential binding of mSpry2 to several key upstream target proteins in the MAP kinase-activating pathway. Thus FGF receptor (FGFR) activation results in increased association of mSpry2 with growth factor receptor-binding protein 2, suc-1-associated nuerotrophic factor target 2, and Raf but decreased binding to protein tyrosine phosphatase 2 and GTPase-activating protein 1, resulting in a net reduction of MAP kinase activation. mSpry2 also spatially translocates to the plasma membrane and intracellular membrane structures in response to FGF10 stimulation. Our data demonstrate novel intracellular mechanisms mediating mSpry2 function as a negative regulator of uncontrolled FGF-induced MAP kinase signaling.

Amino Acid Sequence↗