Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
Lymphology ; 54(3): 133-139, 2021.
Article in English | MEDLINE | ID: mdl-34929074

ABSTRACT

In a thought experiment, a "washing machine" model is proposed based on turbulent flow from complex multi-dimensional forces to characterize fluid dynamics in the brain. The glymphatic system's hypothetical role in this system is illustrated in a series of diagrams. Implications of this model are discussed in terms of normal physiology and a variety of pathologic conditions such as brain atrophy and Alzheimer disease.


Subject(s)
Glymphatic System , Brain , Humans
2.
Lymphology ; 54(1): 23-40, 2021.
Article in English | MEDLINE | ID: mdl-34506085

ABSTRACT

To determine the historical use and utility of various lymphatic imaging modalities in Noonan syndrome (NS) patients, we performed a comprehensive literature review by collecting the published medical imaging of NS lymphatic dysplasias. We correlated imaging findings with clinical phenotypes and treatment. Our analysis of lymphatic imaging modalities provides an algorithmic approach to imaging and patient care across the spectrum of NS developmental defects. A total of 54 NS cases have been published since 1975. Using the observations reported in 15 reviewed publications, an association was made between disruptions in central lymphatic flow and poor clinical presentations/outcomes in NS patients.


Subject(s)
Lymphatic Vessels , Noonan Syndrome , Diagnostic Imaging , Humans , Lymphatic Vessels/diagnostic imaging , Noonan Syndrome/diagnostic imaging , Noonan Syndrome/genetics , Phenotype
3.
Lymphology ; 52(4): 157-165, 2019.
Article in English | MEDLINE | ID: mdl-32171182

ABSTRACT

The number of patients surviving repair of complex congenital heart disease (CCHD) has increased due to improved surgical techniques, post operative management and outpatient care. Likewise, this growing patient population has demonstrated an increasing number and complexity of complications involving the lymphatic system. To evaluate the peripheral and central lymphatic system, whole-body lymphangioscintigraphy (LAS) is considered as the initial imaging evaluation of choice. To date, very few publications exist on the value of lymphatic imaging techniques in infants and small children with lymphatic complications following surgery for congenital heart disease. A retrospective review of medical records from 2008 to 2018 was performed for pediatric patients referred for lymphatic complications after CCHD surgery at an academic medical center. LAS and SPECT/CT was performed using intradermal bipedal injections of Tc 99m labeled filtered sulfur colloid, and in some patients also bilateral hand injections, followed by dynamic imaging and whole- body planar imaging typically up to 180 minutes post injection. Clinical decision making and outcomes were recorded. LAS and SPECT/CT were performed without complication in pediatric patients with prior surgery for CCHD. LAS successfully localized various lymphatic abnormalities such as lymphatic obstruction, reflux, and leaks, which were further delineated by SPECT/CT. LAS findings directed further evaluation with more definitive studies, management and prognosis. Five of the ten patients had follow up outcome data - 2 years and up to 10 years. LAS and SPECT/CT are safe and effective techniques for the initial evaluation of lymphatic abnormalities in pediatric patients with CCHD. LAS, particularly with further 3D localization by SPECT/CT, provides functional imaging of peripheral and central lymphatic flow and thus provides guidance for medical therapy, non operative interventional management, and surgical therapy for these diverse, debilitating, and often life threatening disorders.


Subject(s)
Heart Defects, Congenital/complications , Lymphatic Diseases/diagnosis , Lymphatic Diseases/etiology , Lymphoscintigraphy , Postoperative Complications/diagnosis , Single Photon Emission Computed Tomography Computed Tomography , Whole Body Imaging , Child , Child, Preschool , Female , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/surgery , Humans , Infant , Lymphoscintigraphy/methods , Male , Retrospective Studies , Single Photon Emission Computed Tomography Computed Tomography/methods , Whole Body Imaging/methods
4.
Acta Psychiatr Scand ; 137(1): 30-38, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29141103

ABSTRACT

OBJECTIVE: To examine the associations between personality traits and suicidal ideation (SI) and attempt (SA) in mood disorder patients and community controls. METHOD: We recruited 365 bipolar, 296 major depressive disorder patients, and 315 community controls to assess their lifetime suicidality. Participants filled out self-reported personality questionnaires to collect data of personality traits, including novelty seeking (NS), harm avoidance (HA), extraversion (E), and neuroticism (N). We used logistic regression models adjusted for diagnoses to analyze combinational effects of personality traits on the risk of suicide. Additionally, radar charts display personality profiles for suicidal behaviours by groups. RESULTS: All personality traits were associated with the risk of suicidality with various effect size, except for E that showed protective effect. High N or HA had prominent and independent risk effects on SI and SA. Combinations of high N and low E, or high HA and NS were the risk personality profiles for suicidality. Higher N scores further distinguished SA from SI in mood disorder patients. CONCLUSION: Introvert personality traits showed independent risk effects on suicidality regardless of diagnosis status. Among high-risk individuals with suicidal thoughts, higher neuroticism tendency is further associated with increased risk of suicide attempt.


Subject(s)
Bipolar Disorder/psychology , Depressive Disorder, Major/psychology , Personality , Suicidal Ideation , Suicide, Attempted/psychology , Adult , Case-Control Studies , Exploratory Behavior , Extraversion, Psychological , Female , Humans , Logistic Models , Male , Middle Aged , Neuroticism , Risk Factors , Suicide/psychology , Suicide/statistics & numerical data , Suicide, Attempted/statistics & numerical data , Surveys and Questionnaires
5.
Lymphology ; 50(2): 67-72, 2017.
Article in English | MEDLINE | ID: mdl-30234243

ABSTRACT

Percutaneous intravenous central catheter (PICC) complications are not common and generalized edema and anasarca in neonates as a complication of PICC malposition is even rarer. Documentation of the pathomechanisms of lymphedema in cases of severe anasarca in neonates is not often done. Here we document thoracic duct obstruction as the cause of lymphedema in a neonate with severe nonpitting generalized edema. Most PICC procedures should ideally be guided by point-of-care bedside ultrasound (US), and this precaution may prevent malposition of PICC lines although it will not detect subsequent migration or extravasation.

6.
Int J Obes (Lond) ; 39(8): 1241-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25907313

ABSTRACT

OBJECTIVES: Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity. METHODS: We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways. RESULTS: A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation. CONCLUSION: Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.


Subject(s)
Blood Glucose/metabolism , Inflammation/metabolism , Obesity/metabolism , Adult , Body Fat Distribution , Body Mass Index , Female , Humans , Inflammation/physiopathology , Male , Metabolic Networks and Pathways , Metabolome , Metabolomics/methods , Obesity/physiopathology , Risk Factors , Taiwan
7.
Lymphology ; 47(3): 134-41, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25420306

ABSTRACT

A retrospective study of 67 patients with metastatic melanoma was performed to evaluate if imaging from lymphoscintigraphy could predict a higher miss rate if only the most radioactive node were removed. Following protocol for sentinel node biopsy, the surgeon resected all lymph nodes containing radioactivity > 10% of the most radioactive node. A correlation was performed between the radioactive counts of the lymph nodes and the presence of metastases. The percentage of cases in which the most radioactive node was negative for metastasis on pathology was calculated. Two nuclear medicine physicians read the images from lymphoscintigraphy specifically to determine if the first lymph node visualized became less intense than other nodes on later images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. In 13 of 67 (19%) patients, the most radioactive lymph node was negative for metastasis while a less radioactive node contained metastatic disease. Consensus reading by the nuclear medicine physicians determined that in 9 cases, the first lymph node visualized became less intense than another lymph node on later images. Of the 9 cases, 4 were true positive and 5 were false positive when correlated with intraoperative count rate and pathology. Of the cases where the most radioactive node was not positive on histopathology (n = 13), the consensus reading by the nuclear medicine physicians reported 4 of them (31%). Imaging by lymphoscintigram had a sensitivity 31%, specificity 91%, positive predictive value 44%, and negative predictive value 85% for predicting whether the most radioactive lymph node at surgery would be negative for metastasis at pathology. We conclude that in patients with melanoma, lymphoscintigraphy has high specificity and negative predictive value but modest sensitivity and positive predictive value for detecting when the sentinel node will not be the most radioactive lymph node during sentinel lymph node dissection. These findings support that dynamic imaging by lymphoscintigraphy has a role in surgical planning but that the imaging protocol could benefit from further optimization.


Subject(s)
Lymph Nodes/diagnostic imaging , Lymphoscintigraphy , Melanoma/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Aged , Female , Humans , Lymph Node Excision , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis , Male , Melanoma/secondary , Melanoma/surgery , Middle Aged , Neoplasm Staging , Observer Variation , Predictive Value of Tests , Reproducibility of Results , Retrospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology , Skin Neoplasms/surgery
8.
Minerva Anestesiol ; 80(11): 1158-68, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24569355

ABSTRACT

BACKGROUND: The purpose of this study was to investigate the factors affecting adherence to the low-tidal volume (LTV) strategy in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and their impacts on outcomes. METHODS: This prospective observational study included 111 patients with ALI/ARDS admitted to six intensive care units between March 2010 and February 2011. The patients were divided into the LTV group, which received a TV ≤7.5 mL/kg predicted body weight (PBW), and the non-LTV group, which received a TV >7.5 mL/kg PBW. We studied the association of selected clinical factors and adherence to the LTV strategy, and evaluated their impacts on 28-day mortality and 1-year mortality by the propensity-match process. RESULTS: Adherence to the LTV strategy was only 44%, which was related to lung injury severity (odds ratio [OR]: 3.15, P=0.038), muscle relaxant use (OR: 3.28, P=0.031), and depth of sedation (OR: 0.65, P=0.008). Propensity score-based analysis showed that the LTV group had modestly better 28-day survival (P=0.081) and 1-year survival (P=0.067) than the non-LTV group. Moreover, muscle relaxant use was strongly associated with reducing the risk of death at both 28 days (hazard ratio [HR]: 0.122, 95% confidence interval [CI]: 0.027-0.542, P=0.006) and 1 year ([HR]: 0.111, 95% [CI]: 0.030-0.408, P=0.001). CONCLUSION: Adherence to the LTV strategy was strongly associated with the lung injury score, muscle relaxant use, and depth of sedation. Propensity score-based analysis showed that the use of LTV ventilation and muscle relaxants reduced 28-day and 1-year mortality in ALI/ARDS patients.


Subject(s)
Acute Lung Injury/therapy , Respiration, Artificial/methods , Respiratory Distress Syndrome/therapy , Tidal Volume , Acute Lung Injury/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Muscle Relaxants, Central/therapeutic use , Propensity Score , Prospective Studies , Respiration, Artificial/standards , Respiratory Distress Syndrome/mortality , Treatment Outcome , Young Adult
9.
Article in English | MEDLINE | ID: mdl-24444492

ABSTRACT

OBJECTIVE: Identification of genetic variants that influence bipolar I disorder (BPD-I) through genome-wide association (GWA) studies is limited in Asian populations. The current study aimed to identify novel common variants for BPD-I in an ethnically homogeneous Taiwanese sample using a multi-stage GWA study design. METHOD: At the discovery stage, 200 BPD-I patients and 200 controls that combined to form 16 pools were genotyped with 1 million markers. Utilizing a newly developed rank-based method, top-ranked markers were selected. After validation with individual genotyping, a fine-mapping association study was conducted to identify associated loci using 240 patients and 240 controls. At the last stage, independent samples were collected (351 cases and 341 controls) for replication. RESULTS: Among the top-ranked markers from the discovery stage, eight genes and 15 individual SNPs were evaluated in the fine-mapping stage. At this stage, rs7619173, which is not in a gene coding region, showed the most significant association (P = 2 ∗ 10(-5)) with BPD-I. Four genes had empirical P-values<0.05, including KCNH7 (P = 0.0047), MYST4 (P = 0.0047), NRXN3 (P = 0.0095), and SEMA3D (P = 0.037). For markers genotyped in replication samples, rs7619173 exhibited a significant association (P(combined) = 2 ∗ 10(-4)) after multiple testing correction, while markers rs11001178 (MYST4) and rs2217887 (NRXN3) showed weak associations (P(combined) = 0.02) with BPD-I. CONCLUSION: A multi-stage GWA design has the potential to uncover the underlying pathogenesis of a complex trait. Findings in the present study highlight three loci that warrant further investigation for bipolar.


Subject(s)
Bipolar Disorder/genetics , Genetic Predisposition to Disease/genetics , Histone Acetyltransferases/genetics , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Aged , Ether-A-Go-Go Potassium Channels/genetics , Female , Genome-Wide Association Study , Genotype , Humans , Logistic Models , Male , Middle Aged , Semaphorins/genetics , Taiwan , Young Adult
10.
Eur Psychiatry ; 29(1): 36-43, 2014 Jan.
Article in English | MEDLINE | ID: mdl-23871494

ABSTRACT

Many family characteristics were reported to increase the risk of bipolar disorder (BPD). The development of BPD may be mediated through different pathways, involving diverse risk factor profiles. We evaluated the associations of family characteristics to build influential causal-pie models to estimate their contributions on the risk of developing BPD at the population level. We recruited 329 clinically diagnosed BPD patients and 202 healthy controls to collect information in parental psychopathology, parent-child relationship, and conflict within family. Other than logistic regression models, we applied causal-pie models to identify pathways involved with different family factors for BPD. The risk of BPD was significantly increased with parental depression, neurosis, anxiety, paternal substance use problems, and poor relationship with parents. Having a depressed mother further predicted early onset of BPD. Additionally, a greater risk for BPD was observed with higher numbers of paternal/maternal psychopathologies. Three significant risk profiles were identified for BPD, including paternal substance use problems (73.0%), maternal depression (17.6%), and through poor relationship with parents and conflict within the family (6.3%). Our findings demonstrate that different aspects of family characteristics elicit negative impacts on bipolar illness, which can be utilized to target specific factors to design and employ efficient intervention programs.


Subject(s)
Bipolar Disorder/etiology , Causality , Family Relations , Models, Psychological , Parents/psychology , Adolescent , Adult , Age of Onset , Aged , Bipolar Disorder/epidemiology , Bipolar Disorder/ethnology , Family Characteristics/ethnology , Family Conflict/ethnology , Family Relations/ethnology , Female , Humans , Male , Middle Aged , Parent-Child Relations/ethnology , Taiwan/epidemiology , Taiwan/ethnology , Young Adult
11.
Nutr Diabetes ; 3: e61, 2013 Mar 04.
Article in English | MEDLINE | ID: mdl-23459084

ABSTRACT

BACKGROUND: Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known. METHOD: The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) 25 kg m(-2)) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined. PATIENTS: Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments. RESULTS: APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender-genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014-0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR 1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87-22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007). CONCLUSION: This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

12.
Anaesth Intensive Care ; 41(1): 41-5, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23362891

ABSTRACT

Previous studies have shown that spontaneous breathing trials (SBT) with a T-tube or low-level pressure support are comparable. However, low-level pressure support may overestimate the ability of a patient to sustain spontaneous breathing, resulting in premature extubation. Understanding factors contributing to different responses by patients to the two SBT methods aids in clarifying the limitation of using low-level pressure support for SBT. We performed a prospective observational study in 80 consecutive adult patients with mechanical ventilation to identify the factors contributing to different responses of a patient to the two SBT methods. The 80 patients underwent both a T-tube trial and pressure support ventilation of 6 cmH2O (PS-6) on the day of extubation. Stratified analysis was used to evaluate the effects of age, respiratory compliance and resistance, PaO2/FiO2 ratio and underlying disease on post-SBT responses. Comparing the responses to a T-tube trial and PS-6, the patients with old age, poor pulmonary compliance (≤40 ml/cmH2O) and chronic obstructive pulmonary disease had a higher heart rate (difference [95% CI]: 4 [0,8], 5 [2,9], 5 [0,10] beats/minute, respectively) and systolic blood pressure (10 [4,16], 11 [5,16], 7 [0,13] mmHg, respectively) after the T-tube trial. In conclusion, this research shows that old age and impaired respiratory mechanics contribute to different responses to spontaneous breathing trials with a T-tube and low-level pressure support. Further studies are needed to compare the effectiveness of the two SBT methods in predicting successful extubation in such patient groups.


Subject(s)
Respiration, Artificial/methods , Respiratory Mechanics/physiology , Ventilator Weaning/methods , Age Factors , Aged , Aged, 80 and over , Blood Pressure , Female , Heart Rate , Humans , Male , Oxygen/administration & dosage , Oxygen/metabolism , Prospective Studies , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/therapy , Risk Factors
13.
Equine Vet J ; 42(4): 351-7, 2010 May.
Article in English | MEDLINE | ID: mdl-20525055

ABSTRACT

REASONS FOR PERFORMING STUDY: Differences in racing times have been noted on synthetic track surfaces that appear to depend on the temperature of the track. No published study to date has considered this effect in a systematic manner. OBJECTIVES: To investigate the relationship between temperature of track and speed of horses racing on a synthetic surface. Potential changes in the wax component of the synthetic track were investigated as one possible cause of changes in the track speed at the temperatures observed. METHODS: At Del Mar racetrack (California, USA), the air, surface and subsurface temperatures at 4 depths in the synthetic race surface were measured periodically throughout the day over a 42 day period. The 6 furlong (1.2 km) race (afternoon) and fast training 'work' (morning) times were also compiled. Samples of the track were obtained and the wax separated using a solvent separation technique. Differential scanning calorimetry was used to determine the range of temperatures at which the wax from the track underwent softening and other material changes. Transformation temperatures were compared to temperatures acquired from the track to evaluate the likelihood of changes in the wax properties during racing. RESULTS: Average air, surface and subsurface temperatures changed significantly throughout the day. Temperatures were higher during the afternoon race sessions and race times were significantly slower compared to morning work times. Temperatures at which some of the components of the wax began to soften were found to be within the range of temperature measured during track operation. CONCLUSIONS: A correlation was found between temperature of the synthetic track and speed of horse. Wax separated from the track showed that the temperatures experienced in the surface during normal operation exceed the temperatures at which the wax begins to experience thermal transformation. It is therefore hypothesised that the wax may be a cause of the observed changes in the track performance. POTENTIAL RELEVANCE: Future work should include a study of components of the synthetic track responsible for the change and epidemiological association of risk of injury.


Subject(s)
Horses/physiology , Running/physiology , Sports , Temperature , Animals
14.
Cephalalgia ; 29(8): 883-90, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19236383

ABSTRACT

To investigate the role of plasma calcitonin gene-related peptide (CGRP) in paediatric migraine, we prospectively collected 134 blood samples during or between attacks from 66 migraine, 33 non-migraine headache (non-migraine) and 22 non-headache patients, aged 4-18 years. Plasma CGRP concentrations were measured by enzyme-linked immunosorbent assay and disability by Pediatric MIgraine Disability ASsessment (PedMIDAS) questionnaire. Migraineurs had higher plasma CGRP levels than non-migraine patients (P = 0.007). The attack level was higher than the non-attack level in migraine (P = 0.036), but not in non-migraine, patients. This was also revealed in paired comparison (n = 9, P = 0.015 vs. n = 4, P = 0.47). Using a threshold of 55.1 pg/ml, the sensitivity of the attack level in predicting migraine was 0.81, and specificity 0.75. The PedMIDAS score tended to be higher in the high CGRP (> 200 pg/ml, n = 7) group than in the low (< 200 pg/ml, n = 33) group (26.07 vs. 19.32, P = 0.16) using Mann-Whitney test. Plasma CGRP is useful for diagnosis in paediatric migraine.


Subject(s)
Calcitonin Gene-Related Peptide/blood , Migraine Disorders/blood , Migraine Disorders/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Male , Pediatrics/methods , Reproducibility of Results , Sensitivity and Specificity , Young Adult
15.
Mol Psychiatry ; 12(9): 842-53, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17505468

ABSTRACT

The TAAR6 gene has been previously associated with schizophrenia in 192 pedigrees of European and African ancestry. To replicate these findings we performed an association study of TAAR6 in 265 pedigrees of the Irish Study of High-Density Schizophrenia Families (ISHDSF). Of the 24 genotyped single-nucleotide polymorphisms only rs12189813 and rs9389011 provided single-marker evidence for association (0.0094

Subject(s)
Cell Cycle Proteins/genetics , Family Health , Genetic Linkage , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide , Schizophrenia/genetics , Computational Biology/methods , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Ireland/epidemiology , Male , Models, Molecular , Molecular Weight , Receptors, G-Protein-Coupled , Schizophrenia/physiopathology
16.
Curr Drug Targets ; 8(1): 117-35, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17266536

ABSTRACT

The advance of functional genomics revealed the superfamily of G-protein coupled receptors (GPCRs). Hundreds of GPCRs have been cloned but many of them are orphan GPCRs with unidentified ligands. The first identified orphan GPCR is the opioid receptor like orphan receptor, ORL1. It was cloned in 1994 during the identification of opioid receptor subtypes and was de-orphanized in 1995 by the discovery of its endogenous ligand, nociceptin or orphanin FQ (N/OFQ). This receptor was renamed as N/OFQ peptide (NOP) receptor. Several selective ligands acting at NOP receptors or other anti-N/OFQ agents have been reported. These include N/OFQ-derived peptides acting as agonists (cyclo[Cys(10),Cys(14)]N/OFQ, [Arg(14), Lys(15)]N/OFQ, [pX]Phe(4)N/OFQ(1-13)-NH(2), UFP-102, [(pF)Phe(4),Aib(7), Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)) or antagonists (Phe(1)psi(CH(2)-NH)Gly(2)]N/OFQ(1-13)-NH(2), [Nphe(1)]N/OFQ(1-13)-NH(2), UFP-101, [Nphe(1), (pF)Phe(4),Aib(7),Aib(11),Arg(14),Lys(15)]N/OFQ-NH(2)), hexapeptides, other peptide derivatives (peptide III-BTD, ZP-120, OS-461, OS-462, OS-500), non-peptide agonists (NNC 63-0532, Ro 64-6198, (+)-5a compound, W-212393, 3-(4-piperidinyl)indoles, 3-(4-piperidinyl) pyrrolo[2,3-b]pyridines) and antagonists (TRK-820, J-113397, JTC-801, octahydrobenzimidazol-2-ones, 2-(1,2,4-oxadiazol-5-yl)-1 H-indole, N-benzyl-D-prolines, SB-612111), biostable RNA Spiegelmers specific against N/OFQ, and a functional antagonist, nocistatin. Buprenorphine and naloxone benzoylhydrazone are two opioid receptor ligands showing high affinity for NOP receptors. NOP receptor agonists might be beneficial in the treatment of pain, anxiety, stress-induced anorexia, cough, neurogenic bladder, edema, drug dependence, and, less promising, in cerebral ischemia and epilepsy, while antagonists might be of help in the management of pain, depression, dementia and Parkinsonism. N/OFQ is also involved in cardiovascular, gastrointestinal and immune regulation. Altered plasma levels of N/OFQ have been reported in patients with various pain states, depression and liver diseases. This review summarizes the pharmacological characteristics of, and studies with, the available NOP receptor ligands and their possible clinical implications.


Subject(s)
Drug Delivery Systems/methods , Receptors, Opioid/metabolism , Animals , Humans , Narcotic Antagonists , Opioid Peptides/agonists , Opioid Peptides/antagonists & inhibitors , Opioid Peptides/metabolism , Receptors, Opioid/agonists , Nociceptin Receptor , Nociceptin
17.
Mol Psychiatry ; 11(11): 1025-31, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16940975

ABSTRACT

Because tolerance is an important aspect of alcohol dependence (AD) in humans, recent evidence showing that the Drosophila gene hang is critically involved in the development of alcohol tolerance in the fly suggests that variation in related human loci might be important in the etiology of alcohol-related disorders. The orthology of hang in mammals is complex, but a number of human gene products (including ZNF699) with similar levels of amino-acid identity (18-26%) and similarity (30-41%), are consistently identified as the best matches with the translated hang sequence. We tested for association between the dichotomous clinical phenotype of alcohol dependence and seven single nucleotide polymorphisms (SNPs) in ZNF699 in our sample of 565 genetically independent cases and 496 siblings diagnosed with AD, and 609 controls. In analyses of genetically independent cases and controls, four of the seven single markers show strong evidence for association with AD (0.00003

Subject(s)
Alcohol-Related Disorders/genetics , Carrier Proteins/genetics , Chromosomes, Human, Pair 19/genetics , Transcription Factors/genetics , Zinc Fingers/genetics , Animals , Case-Control Studies , Drosophila Proteins/genetics , Genetic Predisposition to Disease/genetics , Haplotypes , Humans , Linkage Disequilibrium , Polymorphism, Single Nucleotide , Reference Values , Siblings
18.
Mol Psychiatry ; 11(6): 603-11, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16534506

ABSTRACT

Alcoholism is a relatively common, chronic, disabling and often treatment-resistant disorder. Evidence from twin and adoption studies indicates a substantial genetic influence, with heritability estimates of 50-60%. We conducted a genome scan in the Irish Affected Sib Pair Study of Alcohol Dependence (IASPSAD). Most probands were ascertained through alcoholism treatment settings and were severely affected. Probands, affected siblings and parents were evaluated by structured interview. A 4 cM genome scan was conducted using 474 families of which most (96%) were comprised by affected sib pairs. Nonparametric and quantitative linkage analyses were conducted using DSM-IV alcohol dependence (AD) and number of DSM-IV AD symptoms (ADSX). Quantitative results indicate strong linkage for number of AD criteria to a broad region of chromosome 4, ranging from 4q22 to 4q32 (peak multipoint LOD=4.59, P=2.1 x 10(-6), at D4S1611). Follow-up analyses suggest that the linkage may be due to variation in the symptoms of tolerance and out of control drinking. There was evidence of weak linkage (LODs of 1.0-2.0) to several other regions, including 1q44, 13q31, and 22q11 for AD along with 2q37, 9q21, 9q34 and 18p11 for ADSX. The location of the chromosome 4 peak is consistent with results from prior linkage studies and includes the alcohol dehydrogenase gene cluster. The results of this study suggest the importance of genetic variation in chromosome 4 in the etiology and severity of alcoholism in Caucasian populations.


Subject(s)
Alcohol-Related Disorders/genetics , Chromosomes, Human, Pair 4/genetics , Genetic Predisposition to Disease , Aged , Female , Genetic Linkage , Humans , Lod Score , Male , Middle Aged , Pedigree , Siblings , Statistics, Nonparametric
19.
Eur J Clin Microbiol Infect Dis ; 24(8): 559-61, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16096776

ABSTRACT

The study presented here aimed to elucidate the diagnostic value of bacterial stool cultures and viral antigen tests when performed based on the clinical characteristics of acute gastroenteritis in infants and young children. A total of 21 (11.2%) bacterial and 74 (39.6%) viral infections affecting 187 children under the age of 3 years was investigated. Blood (p<0.001) and mucus (p=0.014) in the stool and a C-reactive protein (CRP) level of >or=50 mg/l (p=0.006) were more significantly associated with gastroenteritis of bacterial rather than viral origin. Vomiting (p<0.001) was significantly associated with viral gastroenteritis. Among children with bloody stool, culture grew a Salmonella spp. in 35% and for vomiting children, stool antigen tests detected rotavirus in 60% of cases. In conclusion, etiologic tests to determine the cause of childhood gastroenteritis according to their characteristic clinical features or laboratory test results, or both, are of low diagnostic value.


Subject(s)
Antigens, Viral/analysis , Bacterial Infections/diagnosis , Gastroenteritis/diagnosis , Acute Disease , Bacteria/isolation & purification , Bacterial Infections/therapy , Child, Preschool , Diarrhea, Infantile/diagnosis , Diarrhea, Infantile/microbiology , Disease Management , Feces/microbiology , Feces/virology , Gastroenteritis/microbiology , Gastroenteritis/therapy , Gastroenteritis/virology , Humans , Infant , Infant, Newborn , Rotavirus/isolation & purification
20.
Thorax ; 58(2): 183-4, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12554906

ABSTRACT

The Klippel-Trenaunay syndrome (KTS) is a rare syndrome characterised by the triad of varicose veins, bony and soft tissue hypertrophy, and cutaneous haemangioma. A 30 year old man with KTS with a right mediastinal mass which progressively enlarged over 5 years is described. Computed tomography, magnetic resonance imaging, and bronchial angiography revealed a vascular lesion in the azygous area. After complete excision of the mass, histological examination revealed cavernous haemangioma. To our knowledge, this is the first report of intrathoracic haemangioma in KTS.


Subject(s)
Hemangioma, Cavernous/etiology , Klippel-Trenaunay-Weber Syndrome/complications , Mediastinal Neoplasms/etiology , Adult , Hemangioma, Cavernous/diagnosis , Humans , Magnetic Resonance Imaging/methods , Male , Mediastinal Neoplasms/diagnosis , Tomography, X-Ray Computed/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...