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Biomedical subjects

D Peck

Publications and source records attributed to D Peck.

At least 19 recordsLinked to original sources
PubMed2006

Clinical, enzymatic and molecular characterization of nine new patients with malonyl-coenzyme A decarboxylase deficiency.

We report nine new patients with malonic aciduria associated with enzyme-confirmed malonyl-CoA decarboxylase (MCD) deficiency in eight. Clinical details were available on eight, and molecular genetic characterization was obtained for nine. As for 15 previously described patients, cardinal clinical manifestations included developmental delay and cardiomyopathy; metabolic perturbations (e.g. acidosis) and seizures, however, were infrequent or not observed in our patients. For all, detection of elevated malonic acid in urine (+/- increased C3DC acylcarnitine by analysis employing tandem mass spectrometry) led to pursuit of enzyme studies. MCD activities (nmol/h PER mg protein) revealed: control (n = 22), 16.2 +/- 1.8 (SEM; range 5.7-46.2); patients (n = 8, assayed in duplicate), 1.7 +/- 0.3 (10% of parallel control; range 0.6-2.8). Molecular characterization by DNA sequence analysis and multiplex ligation-dependent probe amplification revealed nine novel mutations (c.796C>T; p.Gln266X, c.481delC; p.Leu161CysfsX18, c.1367A>C; p.Tyr456Ser, c.1319G>T; p.Ser440Ile, c.1430C>T; p.Ser477Phe, c.899G>T; p.Gly300Val, c.799-1683_949-1293del3128, and two other large genomic deletions comprising exons 1 or the complete gene) and two known mutations in the MLYCD gene. Our findings increase the number of enzyme-confirmed MCD-deficient patients by >50%, and expand our understanding of the phenotypic and molecular heterogeneity of this rare disorder.

Adolescent↗
PubMed2005

Variant Creutzfeldt-Jakob disease: a cause for concern. Review of the evidence for risk of transmission through abdominal lymphoreticular tissue surgery.

BACKGROUND: Concern has long existed regarding the possible iatrogenic spread of variant Creutzfeldt-Jakob disease (v-CJD) through surgery. This had been fueled by recent reports of bovine spongiform encephalopathy in U.S. cattle and the first probable case of blood transmission of v-CJD in the UK. METHODS: Systematic review of experimental and nonexperimental studies. Studies identified from searches of Medline, Embase, Cochrane Library, Science Citation Index medical databases, searching bibliographies of retrieved papers, and personal communication with international experts in the field. RESULTS: Six articles satisfied our search criteria. Evidence stems from case reports, case series, and cross-sectional studies. There are no published cases of surgically transmitted v-CJD. CONCLUSION: We found evidence of v-CJD prion agents in the spleen, appendix, rectum, and adrenal glands of affected patients and evidence of v-CJD prion in the appendix of patients in the preclinical stage of the disease. The risk of transmission of v-CJD prion during abdominal surgery is currently unquantifiable.

Abdomen↗
PubMed2004

The relationship between plasma MMP-1, -7, -8 and -13 levels and embolic potential during carotid endoluminal intervention.

BACKGROUND: Patients undergoing carotid endoluminal intervention are at risk of embolic stroke even with the use of distal protection devices. Matrix metalloproteinases (MMPs) have been implicated as a causal factor in plaque instability leading to spontaneous embolisation. We investigated whether plasma MMP levels correlated with the embolisation during carotid endoluminal intervention. METHODS: Thirty circumferentially intact carotid endarterectomy specimens were subjected to a standardised angioplasty procedure in a pulsatile ex vivo model. Emboli collected in a series of distal filters were counted and sized. Plasma samples were collected pre-operatively and analysed for MMP-7 and MMP-8 levels using Western immunoblotting. MMP-1 and MMP-13 levels were determined using ELISA. Emboli number and maximum size were correlated with plasma levels of the MMPs using Spearmans rank. RESULTS: Total MMP-8 levels were related to maximum embolus size (r=0.442, p=0.005) but not emboli number (r=0.342, p=0.052). MMP-1, -7 and -13 were not correlated with either emboli number or with maximum embolus size. CONCLUSION: Pre-operative plasma MMP-8 levels are related to the size of emboli from plaques during carotid endovascular intervention. Further in vivo studies need to be performed to assess the importance of this finding. There is potential for development of plasma markers to identify those patients at greater risk of embolic stroke during carotid endoluminal intervention.

Aged↗
PubMed2001

Intraperitoneal hypothermia during surgery enhances postoperative tumor growth.

BACKGROUND: Recent work has shown that intraoperative hypothermia is a significant source of surgical trauma, with wide-ranging physiological and immunological sequelae. The aim of this study was to examine the effects of intraperitoneal hypothermia during laparoscopy on tumor growth in an animal model. METHODS: Thirty WAG rats were randomized to undergo anesthesia alone (n = 10), insufflation with cold carbon dioxide (CO2) (n = 10), or insufflation with warm CO2 (n = 10). During insufflation, 1 x 105/ml CC531s colon cancer cells in suspension were injected into the peritoneal cavity. The control group was anesthetized and tumor cells were injected without insufflation. After 3 weeks, total tumor weight and the extent of tumor spread, as assessed by the modified Peritoneal Cancer Index (PCI), were compared at autopsy. RESULTS: Laparoscopy with cold CO2 resulted in a significant reduction in local and core body temperatures (p <0.05). Tumor growth in both groups that underwent CO2 pneumoperitoneum was significantly increased compared with the group that did not (p <0.0001, control vs warm CO2 and cold CO2). There was significantly more tumor growth in the rats insufflated with unwarmed CO2 than in the normothermic group (mean total tumor 0.01 g +/- 0.03 vs. 0.043 g +/- 0.07; p = 0.025 Mann-Whitney U test). Tumor spread as shown by the PCI scores was less in the warm gas group than it was in the animals insufflated with cold gas (151 vs 266). CONCLUSIONS: These data demonstrate that the peritoneal insufflation of CO2 enhances tumor growth and that the prevention of perioperative hypothermia during laparoscopy attenuates tumor growth. This effect may be partially mediated by the increased peritoneal trauma that results from insufflation with cold gas.

Animals↗
PubMed1999

Telemedicine for clinical psychology in the Highlands of Scotland.

Telemedicine may be useful in the delivery of clinical psychology services in the Highlands of Scotland, where geographical size and sociodemographic factors can hinder service delivery. The Highlands have a population of 210,000 at a density of approximately 8 people/km2, one of the lowest in the European Union. Despite a general lack of formal evaluation of telemedicine, especially in mental health, descriptive studies and patient satisfaction reports give grounds for optimism. There are several current applications of telemedicine in the Highlands, including cognitive-behavioural therapy, a comparative evaluation of neuropsychological assessments, and the treatment of children and their families. The projects are being formally evaluated and early results are encouraging.

Humans↗
PubMed1998

Time course of ADCw changes in ischemic stroke: beyond the human eye!

BACKGROUND AND PURPOSE: Using newly developed computerized image analysis, we studied the heterogeneity of apparent diffusion coefficient of water (ADCw) values in human ischemic stroke within 10 hours of onset. METHODS: Echo-planar trace diffusion-weighted images from 9 patients with focal cortical ischemic stroke were obtained within 10 hours of symptom onset. An Iterative Self-Organizing Data Analysis (ISODATA) clustering algorithm was implemented to segment different tissue types with a series of DW images. ADCw maps were calculated from 4 DW images on a pixel-by-pixel basis. The segmented zones within the lesion were characterized as low, pseudonormal, or high, expressed as a ratio of the mean+/-SD of ADCw of contralateral noninvolved tissue. RESULTS: The average ADCW in the ischemic stroke region within 10 hours of onset was significantly depressed compared with homologous contralateral tissue (626.6+/-76.8 versus 842.9+/-60.4x10(-6) mm2/s; P<0.0001). Nevertheless, ISODATA segmentation yielded multiple zones within the stroke region that were characterized as low, pseudonormal, and high. The mean proportion of low:pseudonormal:high was 72%:20%:8%. CONCLUSIONS: Despite low average ADCW, computer-assisted segmentation of DW MRI detected heterogeneous zones within ischemic lesions corresponding to low, pseudonormal, and high ADCw not visible to the human eye. This supports acute elevation of ADCw in human ischemic stroke and, accordingly, different temporal rates of tissue evolution toward infarction.

Acute Disease↗
PubMed1998

Hyaluronan-dependent cell migration can be blocked by a CD44 cytoplasmic domain peptide containing a phosphoserine at position 325.

CD44 is the principle transmembrane receptor for the extracellular matrix glycosaminoglycan hyaluronan. This receptor:ligand interaction plays an essential role in a number of physiological events including tumour progression, lymphocyte homing into inflammatory sites and tissue morphogenesis during development. In previous studies we have shown that serine phosphorylation is a critical control mechanism for CD44-dependent cell migration. Here we have investigated the target phosphorylation residues by mutating them individually or in combination. These studies demonstrate that Ser325 is the principle CD44 phosphorylation site and that mutation of this residue blocks CD44-mediated cell migration but not hyaluronan binding. In addition, we show that an upstream Ser323 residue is required as part of the kinase consensus site. To further characterize the role of CD44 phosphorylation, phosphorylated and non-phosphorylated peptides spanning the Ser325 region were synthesised and linked to a 16 amino acid Penetratin sequence to mediate efficient plasma membrane translocation. Peptides containing a phosphoserine at residue 325 are efficient blockers of CD44-mediated cell migration but do not reduce CD44 expression or its ability to bind hyaluronan. These data strongly argue that CD44 adhesion and migration are regulated by distinct mechanisms and that migration requires the specific interaction of intracellular component(s) with phosphorylated CD44 receptors.

Amino Acid Sequence↗
PubMed1998

Discrete domains within the hyaluronan receptor CD44 regulate membrane localization and cell migration.

CD44 is the principle transmembrane receptor for the extracellular matrix glycosaminoglycan, hyaluronan. This receptor: ligand interaction is required for many normal cellular processes including lymphocyte homing into inflammatory sites, assembly of a pericellular matrix during chondrogenesis, wound healing and tissue morphogenesis during development. In order to mediate these diverse events, CD44 expressing cells must be able to regulate, and respond to, interactions with hyaluronan. The mechanisms responsible have been subject to scrutiny over the past few years as it has become clear that their disruption can underlie the progression of both metastatic tumours and chronic inflammatory diseases. Here we describe recent data identifying discrete regions within the transmembrane and cytoplasmic domains of CD44 which regulate this important adhesion receptor.

Animals↗
PubMed1997

The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat.

We have developed a multiparameter magnetic resonance imaging (MRI) cluster analysis model of acute ischemic stroke using T2 relaxation times and the diffusion coefficient of water (ADCw). To test the ability of this model to predict cerebral infarction, male Wistar rats (n = 7) were subjected to 2 h of transient middle cerebral artery (MCA) occlusion, and diffusion and T2 weighted MRI were performed on these rats before, during and up to 7 days after MCA occlusion. MRI tissue signatures, specified by values of ADCw and T2 were assigned to tissue histopathology. Significant correlations were obtained between MRI signatures at different time points and histopathologic measurements of lesion area obtained at 1 week. In addition, we compared the temporal evolution of MRI tissue signatures to a separate population of animals at which histological data were obtained at select times of reperfusion. A significant shift (p < or = 0.05) within signatures reflecting tissue histopathology was demonstrated as the ischemic lesion evolved over time. Our data suggest, that the MRI signatures are associated with the degree of ischemic cell damage. Thus, the tissue signature model may provide a noninvasive means to monitor the evolution of ischemic cell damage and to predict final outcome of ischemic cell damage.

Animals↗
PubMed1997

How do you identify people with severe mental illness in rural communities?

Mental health trusts serving scattered rural communities face particular challenges when attempting to identify and meet unmet need. A number of social, geographical and practical factors are involved. Kim Kirkwood and David Peck describe one such survey, carried out by the Highland Communities NHS Trust, the failure of which raises a number of important issues for practitioners and service planners.

Health Services Accessibility↗
PubMed1996

CD44 phosphorylation regulates melanoma cell and fibroblast migration on, but not attachment to, a hyaluronan substratum.

BACKGROUND: CD44 is a transmembrane receptor for the extracellular matrix glycosaminoglycan, hyaluronan. This receptor-ligand interaction plays an essential role in tumour progression, in embryonic tissue morphogenesis and in leukocyte migration during inflammation. It is well documented that the interaction between CD44 and hyaluronan is strictly regulated, but little is known about the relationship between hyaluronan-dependent cell adhesion and cell migration. RESULTS: In these studies we have used a CD44-negative human melanoma cell line and a murine fibroblast line which expresses low levels of endogenous CD44. Both cell lines were transfected with plasmids encoding wild-type human CD44 or CD44 phosphorylation mutants, in which the target serines had been mutated to small neutral amino acids or large acidic residues. We show that expression of wild-type CD44 enhances the ability of both cell lines to bind to, and migrate on, a hyaluronan-coated substratum. In contrast, the two CD44 phosphorylation mutants were as efficient as wild-type CD44 in mediating cell adhesion but were unable to support hyaluronan-dependent migration. CONCLUSIONS: These studies demonstrate a control mechanism specific for CD44-mediated cell motility and have implications for the regulation of metastatic progression by cell-adhesion receptors.

Animals↗
PubMed1996

The Symptom Questionnaire: British standardization data.

The Symptom Questionnaire is a simple and quick measure of emotional state; previous work has indicated that the Questionnaire has good reliability and validity. However the original sample on which it was based was small, and exclusively North American. Data from a large sample (N = 707) of British psychiatric in-patients, out-patients, day hospital attenders, and a non-patient population sample are presented. Consistent differences between the patient and non-patient samples were obtained on the scales, with a few exceptions; there were no significant differences due to sex.

Affect↗
PubMed1995

A model to predict the histopathology of human stroke using diffusion and T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: We sought to identify MRI measures that have high probability in a short acquisition time to predict, at early time points after onset of ischemia, the eventual development of cerebral infarction in clinical patients who suffer occlusion of a cerebral artery. METHODS: We developed an MR tissue signature model based on experimentally derived relationships of the apparent diffusion coefficient of water (ADCw) and T2 to ischemic brain tissue histopathology. In eight stroke patients we measured ADCw and T2 intensity using diffusion-weighted echo-planar imaging (DW-EPI). Tissue signature regions were defined, and theme maps of the ischemic focus at subacute time points after stroke onset were generated. RESULTS: Five MR signatures were identified in human stroke foci: two that may predict either cell recovery or progression to necrosis, one that may mark the transition to cell necrosis, and two that may be markers of established cell necrosis. CONCLUSIONS: An MR tissue signature model of ischemic histopathology using ADCw and T2 can now be tested for its potential to predict reversible and identify irreversible cellular damage in human ischemic brain regions.

Aged↗