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1.
Pediatr Blood Cancer ; 71(4): e30894, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38296838

ABSTRACT

BACKGROUND: Neonatal hemophagocytic lymphohistiocytosis (nHLH), defined as HLH that presents in the first month of life, is clinically devastating. There have been few large descriptive studies of nHLH. OBJECTIVES: The objective of this study was to perform a meta-analysis of published cases of nHLH. METHODS: A comprehensive literature database search was performed. Cases of HLH were eligible for inclusion if clinical analysis was performed at age ≤30 days. Up to 70 variables were extracted from each case. RESULTS: A total of 544 studies were assessed for eligibility, and 205 cases of nHLH from 142 articles were included. The median age of symptom onset was day of life 3 (interquartile range [IQR]: 0-11, n = 141). Median age at diagnosis was day of life 15 (IQR: 6-27, n = 87). Causes of HLH included familial HLH (48%, n = 99/205), infection (26%, n = 53/205), unknown (17%, n = 35/205), macrophage activation syndrome/rheumatologic (2.9%, n = 4/205), primary immune deficiency (2.0%, n = 5/205), inborn errors of metabolism (2.4%, n = 5/205), and malignancy (2.0%, n = 4/205). Fever was absent in 19% (n = 28/147) of all neonates and 39% (n = 15/38) of preterm neonates. Bicytopenia was absent in 26% (n = 47/183) of patients. Central nervous system (CNS) manifestations were reported in 63% of cases (n = 64/102). Liver injury (68%, n = 91/134) and/or liver failure (24%, n = 32/134) were common. Flow cytometry was performed in 22% (n = 45/205) of cases. Many patients (63%, n = 121/193) died within the period of reporting. Discernable values for HLH diagnostic criteria were reported between 30% and 83% of the time. CONCLUSIONS: Evaluation of nHLH requires rapid testing for a wide range of differential diagnoses. HLH diagnostic criteria such as fever and bicytopenia may not occur as frequently in the neonatal population as in older pediatric populations. Neurologic and hepatic manifestations frequently occur in the neonatal population. Current reports of nHLH suggest a high mortality rate. Future publications containing data on nHLH should improve reporting quality by reporting all clinically relevant data.


Subject(s)
Lymphohistiocytosis, Hemophagocytic , Macrophage Activation Syndrome , Humans , Infant, Newborn , Databases, Factual , Diagnosis, Differential , Fever/diagnosis , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/etiology , Lymphohistiocytosis, Hemophagocytic/epidemiology
2.
Behav Brain Res ; 406: 113229, 2021 05 21.
Article in English | MEDLINE | ID: mdl-33684425

ABSTRACT

Increased neuroinflammation has been shown in individuals diagnosed with schizophrenia (SCHZ). This study evaluated a novel immune modulator (PD2024) that targets the pro-inflammatory cytokine tumor necrosis factor-alpha (TNFα) to alleviate sensorimotor gating deficits and microglial activation employing two different rodent models of SCHZ. In Experiment 1, rats were neonatally treated with saline or the dopamine D2-like agonist quinpirole (NQ; 1 mg/kg) from postnatal day (P) 1-21 which produces increases of dopamine D2 receptor sensitivity throughout the animal's lifetime. In Experiment 2, rats were neonatally treated with saline or the immune system stimulant polyinosinic:polycytidylic acid (Poly I:C) from P5-7. Neonatal Poly I:C treatment mimics immune system activation associated with SCHZ. In both experiments, rats were raised to P30 and administered a control diet or a novel TNFα inhibitor PD2024 (10 mg/kg) in the diet from P30 until P67. At P45-46 and from P60-67, animals were behaviorally tested on auditory sensorimotor gating as measured through prepulse inhibition (PPI). NQ or Poly I:C treatment resulted in PPI deficits, and PD2024 treatment alleviated PPI deficits in both models. Results also revealed that increased hippocampal and prefrontal cortex microglial activation produced by neonatal Poly I:C was significantly reduced to control levels by PD2024. In addition, a separate group of animals neonatally treated with saline or Poly I:C from P5-7 demonstrated increased TNFα protein levels in the hippocampus but not prefrontal cortex, verifying increased TNFα in the brain produced by Poly I:C. Results from this study suggests that that brain TNFα is a viable pharmacological target to treat the neuroinflammation known to be associated with SCHZ.


Subject(s)
Hippocampus/drug effects , Immunomodulating Agents/pharmacology , Microglia/drug effects , Neuroinflammatory Diseases/drug therapy , Prepulse Inhibition/drug effects , Schizophrenia/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Age Factors , Animals , Animals, Newborn , Behavior, Animal/drug effects , Disease Models, Animal , Dopamine Agonists/administration & dosage , Hippocampus/immunology , Hippocampus/metabolism , Hippocampus/physiopathology , Immunomodulating Agents/administration & dosage , Male , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/metabolism , Neuroinflammatory Diseases/physiopathology , Rats , Rats, Sprague-Dawley , Schizophrenia/immunology , Schizophrenia/metabolism , Schizophrenia/physiopathology
3.
Pilot Feasibility Stud ; 7(1): 6, 2021 Jan 04.
Article in English | MEDLINE | ID: mdl-33390189

ABSTRACT

BACKGROUND: Prevalence of depression is increasing in young people, and there is a need to develop and evaluate behavioural interventions which may provide benefits equal to or greater than talking therapies or pharmacological alternatives. Exercise could be beneficial for young people living with depression, but robust, large-scale trials of effectiveness and the impact of exercise intensity are lacking. This study aims to test whether a randomised controlled trial (RCT) of an intervention targeting young people living with depression is feasible by determining whether it is possible to recruit and retain young people, develop and deliver the intervention as planned, and evaluate training and delivery. METHODS: The design is a three-arm cluster randomised controlled feasibility trial with embedded process evaluation. Participants will be help-seeking young people, aged 13-17 years experiencing mild to moderate low mood or depression, referred from three counties in England. The intervention will be delivered by registered exercise professionals, supported by mental health support workers, twice a week for 12 weeks. The three arms will be high-intensity exercise, low-intensity exercise, and a social activity control. All arms will receive a 'healthy living' behaviour change session prior to each exercise session and the two exercise groups are energy matched. The outcomes are referral, recruitment, and retention rates; attendance at exercise sessions; adherence to and ability to reach intensity during exercise sessions; proportions of missing data; adverse events, all measured at baseline, 3, and 6 months; resource use; and reach and representativeness. DISCUSSION: UK National Health Service (NHS) policy is to provide young people with advice about using exercise to help depression but there is no evidence-based exercise intervention to either complement or as an alternative to medication or talking therapies. UK National Institute for Health and Care Excellence (NICE) guidelines suggest that exercise can be an effective treatment, but the evidence base is relatively weak. This feasibility trial will provide evidence about whether it is feasible to recruit and retain young people to a full RCT to assess the effectiveness and cost-effectiveness of an exercise intervention for depression. TRIAL REGISTRATION: ISRCTN, ISRCTN66452702 . Registered 9 April 2020.

4.
IEEE Trans Autom Sci Eng ; 17(4): 2154-2161, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33746640

ABSTRACT

The development of autonomous or semi-autonomous surgical robots stands to improve the performance of existing teleoperated equipment, but requires fine hand-eye calibration between the free-moving endoscopic camera and patient-side manipulator arms (PSMs). A novel method of solving this problem for the da Vinci® robotic surgical system and kinematically similar systems is presented. First, a series of image-processing and optical-tracking operations are performed to compute the coordinate transformation between the endoscopic camera view frame and an optical-tracking marker permanently affixed to the camera body. Then, the kinematic properties of the PSM are exploited to compute the coordinate transformation between the kinematic base frame of the PSM and an optical marker permanently affixed thereto. Using these transformations, it is then possible to compute the spatial relationship between the PSM and the endoscopic camera using only one tracker snapshot of the two markers. The effectiveness of this calibration is demonstrated by successfully guiding the PSM end effector to points of interest identified through the camera. Additional tests on a surgical task, namely grasping a surgical needle, are also performed to validate the proposed method. The resulting visually-guided robot positioning accuracy is better than the earlier hand-eye calibration results reported in the literature for the da Vinci® system, while supporting intraoperative update of the calibration and requiring only devices that are already commonly used in the surgical environment.

5.
Aust Vet J ; 97(4): 116-121, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30919444

ABSTRACT

AIM: To determine the incidence and types of complications associated with oesophageal foreign body (FB) removal in dogs, as well as to evaluate potential risk factors for the development of complications. METHODS: Clinical records were searched within Animal Emergency Service and Veterinary Specialist Services databases between July 2001 and March 2017. Data were collected regarding signalment, FB type, method of removal, medical management and complications. Follow-up records from the referring veterinarian were then obtained by either phone call or email. RESULTS: A total of 349 FB cases were reviewed. The majority of FBs were bones (77.4%), with Staffordshire Bull Terriers (12.3%) and West Highland White Terriers (9.8%) the most common breeds seen. Complications at the time of FB removal occurred in 20 cases (5.9%), with 14 cases of perforation. Persistent gastrointestinal signs were reported in 4.7% of cases within the initial 72-h period following FB removal and 11.9% cases outside this time period. Respiratory signs such as dyspnoea and coughing were also reported in 8 cases (2.3%), all of which occurred within 72 h after FB removal. Follow-up of at least 1 month was available in 151 cases. Delayed complications occurred in 11 cases (7.3%), with stricture occurring in 4 cases (2.6%); 16 animals were either euthanased (n = 14) or died (n = 2) post-FB removal, resulting in a case fatality rate of 4.6%. CONCLUSION: Use of antacid medications and FB type did not have a statistically significant relationship with complications following FB removal.


Subject(s)
Dog Diseases/surgery , Esophagoscopy/veterinary , Foreign Bodies/veterinary , Animals , Antacids/administration & dosage , Breeding , Dogs , Esophageal Perforation/epidemiology , Esophageal Perforation/veterinary , Esophageal Stenosis/epidemiology , Esophageal Stenosis/veterinary , Esophagoscopy/adverse effects , Esophagus/pathology , Esophagus/surgery , Female , Follow-Up Studies , Foreign Bodies/complications , Foreign Bodies/surgery , Incidence , Male , Postoperative Complications/epidemiology , Postoperative Complications/veterinary , Retrospective Studies , Risk Factors , Treatment Outcome
6.
Vet J ; 244: 45-50, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30825894

ABSTRACT

The study objective was to compare temporal-spatial and kinetic gait variables in neurologically normal French bulldogs with and without vertebral kyphosis. French bulldogs presented to a dedicated brachycephalic clinic were prospectively enrolled. All dogs underwent general physical, orthopaedic, and neurological examination prior to study inclusion. The presence of vertebral kyphosis was evaluated by computed tomography and kyphosis was defined as a Cobb angle exceeding 10°. Gait variables were collected using a pressure-sensitive GAITRite walkway with GAITFour software and included measurement of total pressure index (TPI) defined as the sum of peak pressure values recorded from each activated sensor by a paw during mat contact. Fifteen French bulldogs with (n=8) and without kyphosis (n=7) were included. Cobb angle in kyphotic dogs ranged from 14.9° to 39.5°. Univariate analyses were initially performed to examine the association between kyphosis and 16 gait variables. When those variables found to be associated (P<0.2) were taken forward into multivariate generalised linear mixed models (accounting for dog, velocity and side), kyphosis had a significant effect upon TPI of the forelimbs and TPI symmetry ratio (P<0.05); however, the size of these effects was small. Although vertebral kyphosis is rarely associated with neurological deficits, it was associated with subtle alterations in kinetic gait variables (TPI forelimbs and TPI symmetry ratio). Further studies are needed to evaluate the clinical importance of altered gait variables in French bulldogs with kyphosis.


Subject(s)
Dog Diseases/physiopathology , Dogs/physiology , Kyphosis/veterinary , Animals , Dog Diseases/diagnostic imaging , Female , Gait Analysis/veterinary , Kyphosis/diagnostic imaging , Kyphosis/physiopathology , Male , Pedigree , Prospective Studies , Severity of Illness Index
7.
Int J Obes (Lond) ; 39(11): 1630-7, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26063330

ABSTRACT

BACKGROUND: The ability to non-invasively measure body composition in mouse models of obesity and obesity-related disorders is essential for elucidating mechanisms of metabolic regulation and monitoring the effects of novel treatments. These studies aimed to develop a fully automated, high-throughput micro-computed tomography (micro-CT)-based image analysis technique for longitudinal quantitation of adipose, non-adipose and lean tissue as well as bone and demonstrate utility for assessing the effects of two distinct treatments. METHODS: An initial validation study was performed in diet-induced obesity (DIO) and control mice on a vivaCT 75 micro-CT system. Subsequently, four groups of DIO mice were imaged pre- and post-treatment with an experimental agonistic antibody specific for anti-fibroblast growth factor receptor 1 (anti-FGFR1, R1MAb1), control immunoglobulin G antibody, a known anorectic antiobesity drug (rimonabant, SR141716), or solvent control. The body composition analysis technique was then ported to a faster micro-CT system (CT120) to markedly increase throughput as well as to evaluate the use of micro-CT image intensity for hepatic lipid content in DIO and control mice. Ex vivo chemical analysis and colorimetric analysis of the liver triglycerides were performed as the standard metrics for correlation with body composition and hepatic lipid status, respectively. RESULTS: Micro-CT-based body composition measures correlate with ex vivo chemical analysis metrics and enable distinction between DIO and control mice. R1MAb1 and rimonabant have differing effects on body composition as assessed by micro-CT. High-throughput body composition imaging is possible using a modified CT120 system. Micro-CT also provides a non-invasive assessment of hepatic lipid content. CONCLUSIONS: This work describes, validates and demonstrates utility of a fully automated image analysis technique to quantify in vivo micro-CT-derived measures of adipose, non-adipose and lean tissue, as well as bone. These body composition metrics highly correlate with standard ex vivo chemical analysis and enable longitudinal evaluation of body composition and therapeutic efficacy monitoring.


Subject(s)
Adipose Tissue/pathology , Obesity/pathology , X-Ray Microtomography , Adipose Tissue/diagnostic imaging , Animals , Body Composition , Disease Models, Animal , Image Interpretation, Computer-Assisted , Male , Mice , Mice, Obese , Reproducibility of Results , Sensitivity and Specificity
8.
J Evol Biol ; 27(3): 604-15, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24494715

ABSTRACT

Fitness valleys, in which mutations at different loci are singly deleterious but jointly beneficial, arise because of reciprocal sign epistasis. Recent theoretical work provides analytical approximations of times to cross fitness valleys via three mechanisms: sequential fixation, stochastic tunnelling and recombination. These times depend critically on the effective population size (N(e)). Human immunodeficiency virus type 1 (HIV-1) encounters fitness valleys in adapting to its secondary cell-surface chemokine coreceptor, CXCR4. Adaptation to CXCR4 tends to occur late in infection and only in about 50% of patients and is associated with disease progression. It has been hypothesized that the need to cross fitness valleys may explain the delayed and inconsistent adaptation to CXCR4. We have identified four fitness valleys from a previous study of fitness epistasis in adaptation to CXCR4 and use estimates of the within-patient variance N(e) for different patient treatment statuses and infection stages (conditions) to estimate times to cross the valleys. These valleys may be crossed predominantly by stochastic tunnelling, although mean crossing times are consistently longer than the durations of the conditions for which they are calculated. These results were confirmed with stochastic simulation. Simulations show that crossing times for a given condition are highly variable and that for each condition there is a low probability of crossing each valley. These findings support the hypothesis that fitness valleys constrain the adaptation of HIV-1 to CXCR4. This study provides the first detailed analysis of the evolutionary dynamics associated with empirical fitness valleys.


Subject(s)
Adaptation, Physiological , HIV-1/physiology , Receptors, CXCR4/physiology , Humans
9.
Collegian ; 21(4): 287-93, 2014.
Article in English | MEDLINE | ID: mdl-25632725

ABSTRACT

BACKGROUND: Coronary heart disease is common in Type 2 diabetes and often requires cardiac surgery. However poorer outcomes have been reported including increased rates of post-operative infection and prolonged hospital stay. AIM: The aim of the study was to determine the feasibility and acceptability of a specialist consultation model (pre-operative medical and educational intervention) for type 2 diabetes in the cardiac surgery setting. METHODS: Twenty four patients were assigned usual care or to the intervention group. The intervention group were assessed by a diabetes clinical nurse consultant, dietitian, and endocrinologist during a pre-operative visit. Specific diabetes questionnaires were administered, education was delivered, and protocol-driven changes to the medical regimen were instituted. Length of stay, incidence of post-operative complications, and number of post-operative inpatient review endocrinology visits required were recorded. RESULTS: Twenty four patients with a pre-operative HbA(1c) greater than 6.5% (48 mmol/mol) were studied (17 males and 7 females). In the usual care group (n = 15), HbA(1c) pre-operatively was 7.2% (55.2 mmol/mol) compared to 10.1% (86.9 mmol/mol) in the intervention group (n = 9). Six weeks post-operatively HbA(1c) fell significantly in the intervention group by 1.9% (to 8.2% [66.1 mmol/mol]) compared to a reduction of 1.2% (to 7.0% [53 mmol/mol]) in the usual care group (p < 0.05). No significant differences were observed in length of stay in intensive care or in total hospital stay between the groups: length of ICU stay 54 h for intervention versus 47 h for usual care, total hospital stay (mean 8 days for both); or in rates of post-operative infection. Differences were seen between in the diabetes questionnaires: in the Problem Areas in Diabetes questionnaire and in the Diabetes Treatment Satisfaction Questionnaire (p = 0.048). CONCLUSION: This small pilot feasibility study suggests there is potential benefit in the acute optimisation of diabetes treatment before elective cardiac surgery.


Subject(s)
Cardiac Surgical Procedures , Diabetes Mellitus, Type 2/surgery , Aged , Female , Humans , Male , Middle Aged , Preoperative Care
10.
NI 2012 (2012) ; 2012: 263, 2012.
Article in English | MEDLINE | ID: mdl-24199099

ABSTRACT

Technological advances have made it possible to integrate a variety of functions into "smart" wheelchairs that include robotics but also sensors that support telehealth and communication applications. The purpose of this study was to identify possible features that current older adult wheelchair users identify as being most helpful and most important and to use scenarios to determine acceptability of potential features. A small pilot study including 5 wheelchair users residing an assisted living facility was conducted that included a questionnaire and a focus group. The participants identified safety-related features as most helpful and important. Within the scenarios presented, the safety-related features were identified as highly acceptable. Features that were available with current technology (e.g. communication with family) were least highly rated. While more research is needed on user preferences, "smart" wheelchair developers will want to include user preferences and focus on safety and telehealth features.

12.
Clin Toxicol (Phila) ; 48(5): 435-42, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20586573

ABSTRACT

INTRODUCTION: We report a case of digoxin-like toxicity because of ingestion of foraged plants. This patient presented with nausea, vomiting, bradycardia, and hypotension after ingesting Veratrum viride (false hellebore). The patient's serum specimen demonstrated a positive digoxin level (0.38 ng/mL) measured by a clinical tubidimetric immunoassay. We hypothesize that steroidal alkaloid compounds contained in V. viride cross-react with the Multigent Digoxin immunoassay reagent antibodies. RESULTS: Plant extracts from V. viride demonstrated cross-reactivity to Multigent reagent antibodies but did not bind therapeutic DigiFab antibodies. Gas chromatography/mass spectrometry analyses identified several steroidal alkaloid compounds present in the V. viride extracts: jervine, ribigirvine, solanidine, and veratraman. CONCLUSIONS: This study indicates that compounds extracted from V. viride can cross-react with a clinical Digoxin immunoassay. Yet these extracts did not bind DigiFab antibody fragments used for therapeutic intervention. Providers should not unnecessarily administer DigiFab fragments as an antidote in symptomatic V. viride toxic patients.


Subject(s)
Digoxin/blood , Digoxin/immunology , Veratrum , Biological Assay , Bradycardia/complications , Bradycardia/etiology , Chemistry, Clinical , Cross Reactions , Eating , Humans , Hypotension/etiology , Immunoassay/methods , Immunoglobulin Fab Fragments , Nausea/complications , Plant Extracts , Plants/immunology , Veratrum Alkaloids , Vomiting/complications , Vomiting/etiology
13.
Arch Virol ; 153(4): 733-8, 2008.
Article in English | MEDLINE | ID: mdl-18253696

ABSTRACT

The genome structure and organization of a new and distinct caulimovirus that is widespread in dahlia (Dahlia variabilis) was determined. The double-stranded DNA genome was ca. 7.0 kb in size and shared many of the features of the members of the genus Caulimovirus, such as the presence of genes potentially coding for the movement protein, the inclusion body protein, and the reverse transcriptase (RT), and an intergenic region consisting of a potential 35S promoter. However, the virus differed from the previously described dahlia mosaic caulimovirus and other known caulimoviruses in that the aphid transmission factor (ATF) was absent and the putative coat protein contained a C-terminal deletion and was fused in-frame with the RT. Sequence identity at the amino acid level with known caulimoviruses including a previously reported caulimovirus from dahlia was low and ranged from 32 to 72%. The absence of an ATF and the highly divergent nature of the genomic sequence are characteristics of this new caulimovirus that is widely associated with dahlia.


Subject(s)
Caulimovirus/classification , Caulimovirus/genetics , Dahlia/virology , Genome, Viral/genetics , Plant Diseases/virology , Viral Proteins/genetics , Amino Acid Motifs , Amino Acid Sequence , DNA, Viral/genetics , Molecular Sequence Data , Open Reading Frames , Phylogeny , Sequence Analysis, DNA , Species Specificity , Viral Nonstructural Proteins/genetics
14.
Placenta ; 26(5): 372-9, 2005 May.
Article in English | MEDLINE | ID: mdl-15850641

ABSTRACT

Using oligonucleotide microarrays we recently identified a set of transcripts that were up-regulated in hypoxic human trophoblasts. To test the hypothesis that expression of hypoxia-related placental transcripts depends on sampling site we analyzed nine different sites from term human placentas (n=6), obtained after uncomplicated pregnancies. These sites spanned the placental center to the lateral border and the basal to the chorionic plate. Relative gene expression at each site, determined using quantitative PCR, was correlated with villous histology. The expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF), the cytoskeleton proteins lamininA3 and alpha-tubulin, and the signal transduction protein Rad was enhanced in the subchorionic lateral border compared to medial basal site (1.6-2.9 fold, p<0.05). In contrast, the expression of NDRG1, adipophilin and human placental lactogen was unchanged. Enhanced villous maturation, syncytial knots and fibrin deposits were more frequent in the subchorionic placental lateral border, and correlated with up-regulation of hypoxia-related transcripts (p<0.05). The association between sample site and expression level was not observed in placentas with marginal cord insertion. The expression of hypoxia-related genes in the term human placenta is dependent on sampling site within the placental disk, likely reflecting local differences in villous perfusion.


Subject(s)
Gene Expression , Placenta/anatomy & histology , Placenta/metabolism , Base Sequence , Cell Cycle Proteins , Connective Tissue Growth Factor , DNA, Complementary/genetics , Female , Gene Expression Profiling , Humans , Immediate-Early Proteins/genetics , Intercellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins , Laminin/genetics , Membrane Proteins/genetics , Oligonucleotide Array Sequence Analysis , Perilipin-2 , Polymerase Chain Reaction , Pregnancy , Proteins/genetics , Tubulin/genetics , Vascular Endothelial Growth Factor A/genetics , ras Proteins/genetics
15.
Aging Cell ; 2(1): 59-69, 2003 02.
Article in English | MEDLINE | ID: mdl-12882335

ABSTRACT

Selective vulnerability of particular groups of neurons is a characteristic of the aging nervous system. We have studied the role of neurotrophin (NT) signalling in this phenomenon using rat sympathetic (SCG) neurons projecting to cerebral blood vessels (CV) and iris which are, respectively, vulnerable to and protected from atrophic changes during old age. RT-PCR was used to examine NT expression in iris and CV in 3- and 24-month-old rats. NGF and NT3 expression in iris was substantially higher compared to CV; neither target showed any alterations with age. RT-PCR for the principal NT receptors, trkA and p75, in SCG showed increased message during early postnatal life. However, during mature adulthood and old age, trkA expression remained stable while p75 declined significantly over the same period. In situ hybridization was used to examine receptor expression in subpopulations of SCG neurons identified using retrograde tracing. Eighteen to 20 h following local treatment of iris and CV with NGF, NT3 or vehicle, expression of NT receptor protein and mRNA was higher in iris- compared with CV-projecting neurons from both young and old rats. NGF and NT3 treatment had no effect on NT receptor expression in CV-projecting neurons at either age. However, similar treatment up-regulated p75 and trkA expression in iris-projecting neurons from 3-month-old, but not 24-month-old, rats. We conclude that lifelong exposure to low levels of NTs combined with impaired plasticity of NT receptor expression are predictors of neuronal vulnerability to age-related atrophy.


Subject(s)
Adrenergic Fibers/metabolism , Aging/physiology , Neurons/metabolism , Receptor, trkA/metabolism , Receptor, trkC/metabolism , Receptors, Nerve Growth Factor/metabolism , Animals , Cerebrovascular Circulation , In Situ Hybridization , Iris/cytology , Iris/innervation , Iris/metabolism , Nerve Growth Factors/genetics , Nerve Growth Factors/metabolism , Rats , Receptor, Nerve Growth Factor , Receptor, trkA/genetics , Receptor, trkC/genetics , Receptors, Nerve Growth Factor/genetics , Signal Transduction/physiology , Superior Cervical Ganglion/cytology , Superior Cervical Ganglion/metabolism
16.
Am Heart J ; 146(1): 62-8, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12851609

ABSTRACT

BACKGROUND: Sphingolipids are emerging as important signaling molecules that may be produced by cardiac tissue during ischemic stress or as a consequence of inflammation. Because both inflammation and myocardial ischemia are associated with coronary artery disease (CAD), a study was designed to test the ability of serum sphingolipids to predict obstructive CAD. METHODS: The study consisted of 308 consecutive patients undergoing coronary angiography for all indications. The primary data points were the assessment of coronary artery stenosis with angiography and the measurements of serum sphingolipids. RESULTS: In this diverse population, serum sphingosine-1-phosphate (S1P) was a significant predictor of CAD (P <.001). Multivariate analysis with logistic regression demonstrated that serum S1P was more predictive of obstructive CAD (odds ratio = 7.61) than the traditional risk factors (age, sex, family history of CAD, diabetes mellitus, lipid profile, hypertension, etc.). A 3-variable S1PC composite score was derived by combining the power of the S1P marker with the 2 most important risk factors, age and sex. The relationship between the S1PC and CAD scores was continuous and progressive, such that patients with elevated S1PC scores had higher occurrences of obstructive CAD. S1PC was also predictive of disease severity; 53.2% of patients in the fourth S1PC quartile had 2 to 3 vessel CAD, whereas only 5.2% of patients in the first S1PC quartile had 2 to 3 vessel disease (RR = 10.2 for severity). CONCLUSIONS: Serum S1P is a remarkably strong and robust predictor of both the occurrence and severity of coronary stenosis. An S1P-based composite score may be useful as a novel, non-invasive indicator of obstructive CAD.


Subject(s)
Biomarkers/blood , Coronary Artery Disease/blood , Lysophospholipids , Sphingosine/analogs & derivatives , Sphingosine/blood , Adult , Aged , Aged, 80 and over , Analysis of Variance , Female , Humans , Logistic Models , Male , Middle Aged , Risk Factors , Severity of Illness Index
17.
J Clin Hypertens (Greenwich) ; 4(3): 189-96, 2002.
Article in English | MEDLINE | ID: mdl-12045368

ABSTRACT

Obesity, now recognized as an independent risk factor for cardiovascular disease, is closely associated with hypertension. Complex mechanisms link increasing body weight with increasing blood pressure. Treatment of the obese patient with hypertension requires consideration of physiologic changes related to obesity hypertension. Lifestyle modification, including weight reduction and increased physical activity, can directly influence blood pressure levels and improve blood pressure control in obese, hypertensive patients. Clinical trials are needed to determine the most effective antihypertensive drugs for the obese, hypertensive patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity hypertension, but additional long-term studies are needed to support their safety and efficacy.


Subject(s)
Hypertension/epidemiology , Hypertension/therapy , Obesity/epidemiology , Obesity/therapy , Adult , Aged , Antihypertensive Agents/therapeutic use , Combined Modality Therapy , Comorbidity , Diet, Fat-Restricted , Exercise , Female , Humans , Incidence , Life Style , Male , Middle Aged , Prognosis , Risk Assessment , Risk Factors , Treatment Outcome
18.
Tissue Eng ; 8(2): 309-19, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12031119

ABSTRACT

Soft tissue reconstruction using tissue-engineered constructs requires the development of materials that are biocompatible and support cell adhesion and growth. The objective of this study was to evaluate the use of macroporous hydrogel fragments that were formed using either unmodified alginate or alginate covalently linked with the fibronectin cell adhesion peptide RGD (alginate-RGD). These materials were injected into the subcutaneous space of adult, domesticated female sheep and harvested for histological comparisons at 1 and 3 months. In addition, the alginate-RGD porous fragments were seeded with autologous sheep preadipocytes isolated from the omentum, and these cell-based constructs were also implanted. The results from this study indicate that both the alginate and alginate-RGD subcutaneous implants supported tissue and vascular ingrowth. Furthermore, at all time points of the experiment, a minimal inflammatory response and capsule formation surrounding the implant were observed. The implanted materials also maintained their sizes over the 3-month study period. In addition, the alginate-RGD fragments supported the adhesion and proliferation of sheep preadipocytes, and adipose tissue was present within the transplant site of these cellular constructs, which was not present within the biomaterial control sites.


Subject(s)
Adipose Tissue/cytology , Adipose Tissue/physiology , Alginates/administration & dosage , Biocompatible Materials/pharmacology , Hydrogel, Polyethylene Glycol Dimethacrylate/administration & dosage , Absorbable Implants , Adipose Tissue/diagnostic imaging , Analysis of Variance , Animals , Cross-Linking Reagents , Glucuronic Acid , Hexuronic Acids , Injections, Subcutaneous , Oligopeptides , Radiography , Sheep , Tissue Engineering/methods
19.
Rheumatology (Oxford) ; 40(11): 1274-8, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11709611

ABSTRACT

OBJECTIVE: Juvenile idiopathic arthritis (JIA) can affect a child's performance across a range of activities necessary to normal childhood development. Although there are now several available measures of disability in JIA, none have been validated for use with children in the UK. Consequently, a study was undertaken to compare and validate four such measures, together with a locally developed function test. METHODS: Fifty-three children between the ages of 5 and 16 yr were recruited into the study. The mean age was 10.4 yr and mean duration of disease 4 yr. Seventy per cent were female. RESULTS: Internal consistency was adequate in three of five measures. Four of five measures showed the expected associations between disease activity and function (P<0.05). The level of reliability was poor for tests that involved direct assessment by therapists. Most showed poor levels of unidimensionality. CONCLUSION: Until new measures become available, the CHAQ appears to be the current 'best buy' for measuring function in children with arthritis.


Subject(s)
Arthritis, Juvenile/physiopathology , Disability Evaluation , Adolescent , Arthritis, Juvenile/diagnosis , Child , Child, Preschool , Female , Humans , Male , Psychometrics , Reproducibility of Results , Treatment Outcome
20.
Arch Virol ; 146(8): 1581-98, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11676419

ABSTRACT

Polymerase chain reaction (PCR) was applied to detect and establish provisional identity of begomoviruses through amplification of a approximately 575 bp fragment of the begomoviral coat protein gene (CP), referred to as the 'core' region of the CP gene (core CP). The core CP fragment contains conserved and unique regions, and was hypothesized to constitute a sequence useful for begomovirus classification. Virus relationships were predicted by distance and parsimony analyses using the A component (bipartite viruses) or full genome (monopartite viruses), CP gene, core CP, or the 200 5'-nucleotides (nt) of the CP. Reconstructed trees and sequence divergence estimates yielded very similar conclusions for all sequence sets, while the CP 5'-200 nt was the best strain discriminator. Alignment of the core CP region for 52 field isolates with reference begomovirus sequences permitted provisional virus identification based on tree position and extent of sequence divergence. Geographic origin of field isolates was predictable based on phylogenetic separation of field isolates examined here. A 'closest match' or genus-level identification could be obtained for previously undescribed begomoviruses using the BLAST program to search a reference core CP database located at our website and/or in GenBank. Here, we describe an informative molecular marker that permits provisional begomovirus identification and classification using a begomoviral sequence that is smaller than the presently accepted, but less accessible CP sequence.


Subject(s)
Capsid/genetics , Geminiviridae/classification , Geminiviridae/genetics , Plant Diseases/virology , Plants/virology , DNA, Viral/analysis , Databases, Nucleic Acid , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction , Reference Standards , Sequence Analysis, DNA
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