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Functional Abnormalities (functional + abnormality)
Selected AbstractsAtaxic mutant mice with defects in Ca2+ channel ,1A subunit gene: morphological and functional abnormalities in cerebellar cortical neuronsCONGENITAL ANOMALIES, Issue 2 2000Kazuhiko Sawada ABSTRACT This review summarizes recent studies in the morphological and functional abnormalities of cerebella in three ataxic mutant mice, i.e. tottering mouse, leaner mouse, and rolling mouse Nagoya (RMN). These mutants carry mutations in the Ca2+ channel ,1A subunit gene, and become useful models for human neurological diseases such as episodic ataxia type-2, familial hemiplegic migraine, and spinocerebellar ataxia type-6. All three mutants exhibited altered morphology of the Purkinje cells, ectopic synaptic contacts between granule cell axons (parallel fibers) and Purkinje cell dendritic spines and abnormal expression of tyrosine hydroxylase in Purkinje cells. In leaner mice, Purkinje cell loss was observed in alternating sagittal compartments of the cerebellar cortex corresponding to the Zebrin II-negative zones. The mutated Ca2+ channel ,1A subunit was highly expressed in granule and Purkinje cells, and the P-type Ca2+ currents in Purkinje cells were selectively reduced in the mutant mice. Therefore, we concluded that altered Ca2+ currents through the mutated Ca2+ channel ,1A subunit might be involved in the functional and morphological abnormalities in granule and Purkinje cells, and might result in expressions of behavioral phenotypes including ataxia. Increased levels of corticotropin-releasing factor and cholecystokinin in some climbing and mossy fibers were observed in RMN. These neuropeptides modulated the excitability of granule and Purkinje cells, indicating the possible expression of ataxic symptoms. [source] Ophthalmological, cognitive, electrophysiological and MRI assessment of visual processing in preterm children without major neuromotor impairmentDEVELOPMENTAL SCIENCE, Issue 5 2010Michelle O'Reilly Many studies report chronic deficits in visual processing in children born preterm. We investigated whether functional abnormalities in visual processing exist in children born preterm but without major neuromotor impairment (i.e. cerebral palsy). Twelve such children (< 33 weeks gestation or birthweight < 1000 g) without major neuromotor impairment and 12 born full-term controls were assessed at 8,12 years of age by means of ophthalmological assessment (visual acuity, colour vision, stereopsis, stereoacuity, visual fields, ocular motility, motor fusion), cognitive tests of visual-motor, visual-perceptual and visual-spatial skills and pattern-reversal visual evoked potentials (PR-VEPs). All participants also underwent magnetic resonance imaging (MRI) of the brain and neuromotor assessments. No significant differences were found between the groups on the ophthalmological, visual cognitive, neurological, neuromotor or MRI measures. The P100 component of the PR-VEP showed a significantly shorter latency in the preterm compared with the full-term participants. Whilst this P100 finding suggests that subtle abnormalities may exist at the neurophysiological level, we conclude that visual dysfunction is not systematically associated with preterm birth in the context of normal neurological status. [source] An Abnormal Right Ventricular Apical Angle is Indicative of Global Right Ventricular ImpairmentECHOCARDIOGRAPHY, Issue 5 2006Angel López-Candales M.D. The presence of right ventricular (RV) dysfunction is an adverse prognostic indicator but current echocardiographic methods have some limitations. RV apical angles in systole and diastole were correlated with known parameters of RV function in patients without pulmonary hypertension (Group 1) and in patients with pulmonary hypertension (Group 2). RV apical angles were significantly smaller in both systole (22 ± 7°) and diastole (33 ± 6°) in Group 1 patients when compared to Group 2 (54 ± 18°, p < 0.0001 and 59 ± 17°, p < 0.0001, respectively). RV apical angles, both in systole and diastole, were strongly correlated with RV end-systolic area (R = 0.89, p < 0.0001) and end-diastolic area (R = 0.81, p < 0.0001), respectively. Similarly, the apical systolic and diastolic angle correlated well with decreased tricuspid annular plane systolic excursion (TAPSE, R =,0.76 and R =,0.73, p < 0.001) as well as with decreased RV fractional area change (R =,0.81 and R =,0.77, p < 0.001). Therefore, we conclude that this new measurement of RV apical angle is simple and useful to quantify RV apical structural and functional abnormalities that are well correlated with global RV impairment in patients with chronic pulmonary hypertension. [source] PRECLINICAL STUDY: FULL ARTICLE: Altered architecture and functional consequences of the mesolimbic dopamine system in cannabis dependenceADDICTION BIOLOGY, Issue 3 2010Saturnino Spiga ABSTRACT Cannabinoid withdrawal produces a hypofunction of mesencephalic dopamine neurons that impinge upon medium spiny neurons (MSN) of the forebrain. After chronic treatment with two structurally different cannabinoid agonists, ,9 -tetrahydrocannabinol and CP55 940 (CP) rats were withdrawn spontaneously and pharmacologically with the CB1 antagonist SR141716A (SR). In these two conditions, evaluation of tyrosine hydroxylase (TH)-positive neurons revealed significant morphometrical reductions in the ventrotegmental area but not substantia nigra pars compacta of withdrawn rats. Similarly, confocal analysis of Golgi,Cox-stained sections of the nucleus accumbens revealed a decrease in the shell, but not the core, of the spines' density of withdrawn rats. Administration of the CB1 antagonist SR to control rats, provoked structural abnormalities reminiscent of those observed in withdrawal conditions and support the regulatory role of cannabinoids in neurogenesis, axonal growth and synaptogenesis by acting as eu-proliferative signals through the CB1 receptors. Further, these measures were incorporated into a realistic computational model that predicts a strong reduction in the excitability of morphologically altered MSN, yielding a significant reduction in action potential output. These pieces of evidence support the tenet that withdrawal from addictive compounds alters functioning of the mesolimbic system and provide direct morphological evidence for functional abnormalities associated with cannabinoid dependence at the level of dopaminergic neurons and their postsynaptic counterpart and are coherent with recent hypothesis underscoring a hypodopaminergic state as a distinctive feature of the ,addicted brain'. [source] Effect of the lactic acid bacterium Streptococcus thermophilus on stratum corneum ceramide levels and signs and symptoms of atopic dermatitis patientsEXPERIMENTAL DERMATOLOGY, Issue 5 2003Luisa Di Marzio Abstract:, A reduced amount of total ceramides could be responsible for functional abnormalities of the skin of atopic dermatitis (AD) patients. The ability of an experimental cream containing sonicated Streptococcus thermophilus to increase skin ceramide levels in healthy subjects has been previously reported. The aim of the present work was to investigate the effects of the topical administration of a S. thermophilus -containing cream on ceramide levels of stratum corneum from AD patients. A 2-week application of the cream, containing a sonicated preparation of the lactic acid bacterium S. thermophilus, in the forearm skin of 11 patients led to a significant and relevant increase of skin ceramide amounts, which could have resulted from the sphingomyelin hydrolysis through the bacterial sphingomyelinase. Moreover, in all patients the topical application of our experimental cream also resulted in the improvement of the signs and symptoms characteristic of AD skin (i.e. erythema, scaling, pruritus). [source] Dynamic Assessment of Abnormalities in Central Pain Transmission and Modulation in Tension-type Headache SufferersHEADACHE, Issue 2 2000Jonathan D. Neufeld PhD Objective.,To examine and compare central pain processing and modulation in young tension-type headache sufferers with that of matched healthy controls using an induced headache "challenge" paradigm. Background.,Recent research has suggested that abnormalities in central pain processing and descending pain modulation may contribute to chronic tension-type headache. These abnormalities, if they contribute to headache pathogenesis, should be present in young adult tension-type headache sufferers. Recent research using static measures of physiological variables, such as muscle tenderness and exteroceptive suppression, has identified chronic muscle tenderness as a characteristic of young tension-type headache sufferers, but other central nervous system functional abnormalities may require a dynamic "challenge" to be observed. Methods.,Twenty-four young women meeting the International Headache Society diagnostic criteria for tension-type headache (headache-prone) and a matched group of 24 healthy women who reported fewer than 10 problem headaches per year (control) participated in a double-blind, placebo-controlled, crossover study. Subjects completed jaw clenching and a placebo condition on different days in counterbalanced order. Pericranial muscle tenderness, pressure-pain thresholds on the temporalis, and exteroceptive suppression periods were assessed before and after each procedure. Head pain was recorded for 12 to16 hours following each condition. Results.,Headache-prone subjects were more likely than controls to experience headaches after both the jaw clenching and placebo procedures, but neither group was significantly more likely to experience headaches following jaw clenching than placebo. In pretreatment measurements, headache-prone subjects exhibited greater muscle tenderness than controls, but pressure-pain detection thresholds and exteroceptive suppression periods did not differ in the two groups. Control subjects showed increases in muscle tenderness and exteroceptive suppression periods following both the clenching and placebo procedures, whereas headache-prone subjects exhibited no significant changes in any of the physiological measures following either experimental manipulation. Conclusions.,These results confirm previous findings indicating abnormally high pericranial muscle tenderness in young tension headache sufferers even in the headache-free state. In addition, the results suggest that the development of headaches following noxious stimulation is more strongly related to headache proneness and associated abnormalities in central pain transmission or modulation (indexed by pericranial muscle tenderness and exteroceptive suppression responses) than muscle strain induced by jaw clenching. [source] Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophreniaHUMAN BRAIN MAPPING, Issue 12 2009Bumseok Jeong Abstract Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract-based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Changes in oxidative balance in rat pericytes exposed to diabetic conditionsJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2004A. Manea Abstract Recent data indicate that the oxidative stress plays an important role in the pathogenesis of diabetes and its complications such as retinopathy, nephropathy and accelerated atherosclerosis. In diabetic retinopathy, it was demonstrated a selective loss of pericytes accompanied by capillary basement membrane thickening, increased permeability and neovascularization. This study was designed to investigate the role of diabetic conditions such as high glucose, AGE-Lysine, and angiotensin II in the modulation of antioxidant enzymes activities, glutathione level and reactive oxygen species (ROS) production in pericytes. The activity of antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total glutathione (GSH) was measured spectrophotometrically. The production of ROS was detected by spectrofluorimetry and fluorescence microscopy after loading the cells with 2,-7, dichlorofluoresceine diacetate; as positive control H2O2 was used. Intracellular calcium was determined using Fura 2 AM assay. The results showed that the cells cultured in high glucose alone, do not exhibit major changes in the antioxidant enzyme activities. The presence of AGE-Lys or Ang II induced the increase of SOD activity. Their combination decreased significantly GPx activity and GSH level. Athree times increase in ROS production and a significant impairment of intracellular calcium homeostasis was detected in cells cultured in the presence of the three pro-diabetic agents used. In conclusion, our data indicate that diabetic conditions induce in pericytes: (i) an increase of ROS and SOD activity, (ii) a decrease in GPx activity and GSH level, (iii) a major perturbation of the intracellular calcium homeostasis. The data may explain the structural and functional abnormalities of pericytes characteristic for diabetic retinopathy. [source] Heart failure: a hemodynamic disorder complicated by maladaptive proliferative responsesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2003A. M. Katz Abstract Heart failure has traditionally been viewed as a hemodynamic syndrome characterized by fluid retention, high venous pressure, and low cardiac output. Over the past decade, however, it has become clear that because of deterioration and progressive dilatation (remodeling) of the diseased heart, this is also a rapidly fatal syndrome. The importance of prognosis came to be appreciated when clinical trials showed that therapy which initially improves such functional abnormalities, as high venous pressure and low cardiac output, often fail to improve survival, and that some drugs which improve hemodynamics worsen long-term prognosis. The latter is true for most vasodilators which, in spite of alleviating the adverse short-term consequences of high afterload, shorten survival. Notable exceptions are ACE inhibitors, whose vasodilator effects do not explain their ability to prolong survival; instead, these drugs slow both deterioration and remodeling of the failing heart. Inotropic agents, while providing immediate relief of symptoms, generally shorten long-term survival, whereas ,-blockers slow deterioration and remodeling, and reduce mortality. Aldosterone antagonists exert beneficial effects on prognosis that are not easily explained by their diuretic effects, but instead can be explained by their ability to inhibit signaling pathways that stimulate maladaptive hypertrophy, remodeling, apoptosis and other deleterious responses that cause deterioration of the failing heart. These and other findings demonstrate that heart failure is more than a hemodynamic disorder; these patients suffer from maladaptive proliferative responses that cause cardiac cell death and progressive dilatation that play a key role in determining the poor progressive in this syndrome. [source] Ethanol exposure during embryogenesis decreases the radial glial progenitorpool and affects the generation of neurons and astrocytesJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Gemma Rubert Abstract Prenatal ethanol exposure induces functional abnormalities during brain development affecting neurogenesis and gliogenesis. We have previously reported that alcohol exposure during embryogenesis disrupts radial glia (RG) and gliogenesis. Taking into account the new role of RG as neural progenitors, we have investigated whether ethanol affects RG as a neural stem cell. We found that in utero ethanol exposure impairs cell proliferation and decreases neurons and astrocytes generated in cultured RG and in embryonic cerebral cortex. Telencephalic cultures obtained at E12 from ethanol-treated rats displayed a reduction in the proportion of actively dividing RG progenitors, as demonstrated by 5-bromo-2,-deoxyuridine incorporation, and in the percentage of brain lipid binding protein-positive RG. Consistently, neurosphere formation assay from E12 telencephalon showed a reduced number of multipotent progenitor cells in cultures isolated from ethanol-treated rats in comparison with pair-fed control group. Moreover, levels of activated Notch1 and fibroblast growth factor receptor 2, which regulate the maintenance of the progenitor state of RG, are decreased by prenatal ethanol exposure. These findings demonstrate that ethanol reduces the telencephalic RG progenitor pool and its transformation into neurons and astrocytes, which may contribute to an explanation of the defects in brain function often observed in fetal alcohol syndrome. © 2006 Wiley-Liss, Inc. [source] Fibrinogens Kosai and Ogasa: B,15Gly,Cys (GGT,TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregationJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003M. Hirota-Kawadobora Summary., We found two heterozygous dysfibrinogenemias, designated fibrinogen Kosai and fibrinogen Ogasa. Kosai was associated with arteriosclerosis obliterans but Ogasa showed no bleeding or thrombotic tendencies. The plasma fibrinogen concentrations from the two propositi (Ogasa and Kosai) were much lower when determined by the thrombin-time method (0.94 and 1.06 g L,1, respectively) than when determined by the immunological method (2.87 and 2.72 g L,1, respectively). We performed DNA sequencing and functional analyses to clarify the relationship between the structural and functional abnormalities. Genetic analysis of PCR-amplified DNA from the propositi identified the heterozygous substitution B,15Gly,Cys (GGT,TGT). Western blotting analysis of purified fibrinogen revealed the existence of albumin,fibrinogen complexes. Functional analyses indicated that compared with the normal control, the propositi's fibrinogen released only half the normal amount of fibrinopeptide B and showed markedly impaired polymerization. In addition, the observation of thinner fibers in fibrin clots (by scanning electron microscopy) indicated markedly defective lateral aggregation in the variant fibrinogens. The impaired functions may be due to the substitution of Cys for B,o15Gly plus the existence of some additional disulfide-bonded forms. [source] Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's crampMOVEMENT DISORDERS, Issue 1 2007Tobias Bäumer MD Abstract Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients. © 2006 Movement Disorder Society [source] Relationship between induced sputum cytology and inflammatory status with lung structural and functional abnormalities in asbestosisAMERICAN JOURNAL OF INDUSTRIAL MEDICINE, Issue 3 2008José Henrique Setta MD Abstract Background Asbestosis is associated with lung cellular and immunological abnormalities. Induced sputum cytology and local and systemic markers of inflammation may be helpful to characterize disease status and progression in these patients. Methods Thirty-nine ex-workers with asbestosis on high-resolution CT (HRCT) and 21 non-exposed controls were evaluated. Sputum cytology and IL-8 in serum and sputum were related to lung function impairment. Results Subjects with asbestosis had reduced sputum cellularity but higher macrophage/neutrophil ratio and % macrophage as compared with controls. Sputum and serum IL-8 were also higher in patients with asbestosis (P,<,0.05). In addition, evidence of lung architectural distorption on HRCT was associated with increased levels of serum IL-8. Interestingly, absolute macrophage number was negatively correlated with total lung capacity (r,=,,0.40; P,=,0.04) and serum IL-8 to lung diffusing capacity (r,=,,0.45; P,=,0.01). Conclusions Occupationally exposed subjects with asbestosis on HRCT have cytologic abnormalities in induced sputum and increased local and systemic pro-inflammatory status which are correlated to functional impairment. Am. J. Ind. Med. 51:186,194, 2008. © 2008 Wiley-Liss, Inc. [source] Anterior cingulate cortex volume reduction in patients with panic disorderPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2008Takeshi Asami md Aim:, Recent neuroimaging studies have suggested that the anterior cingulate cortex (ACC) has an important role in the pathology of panic disorder. Despite numerous functional neuroimaging studies that have elucidated the strong relationship between functional abnormalities of the ACC and panic disorder and its symptoms and response to emotional tasks associated with panic disorder, there has been no study showing volumetric changes of the ACC or its subregions. Methods:, To clarify the structural abnormalities of ACC and its subregions, the combination of region of interest (ROI) and optimized voxel-based morphometry (VBM) methods were performed on 26 patients with panic disorder, and 26 age and sex-matched healthy subjects. In the ROI study, ACC was divided into four subregions: dorsal, rostral, subcallosal and subgenual ACC. Results:, The results of the manually traced ROI volume comparison showed significant volume reduction in the right dorsal ACC. VBM also showed a volume reduction in the right dorsal as well as a part of the rostral ACC as a compound mass. Conclusions:, Both manual ROI tracing and optimized VBM suggest a subregion-specific pattern of ACC volume deficit in panic disorder. In addition to functional abnormalities, these results suggest that structural abnormalities of the ACC contribute to the pathophysiology of panic disorder. [source] Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controlsTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 3 2009Rozmin Halari Background:, There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. Methods:, Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14,17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). Results:, In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. Conclusions:, This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD. [source] Comparisons of structural and functional abnormalities in mouse b-wave mutantsTHE JOURNAL OF PHYSIOLOGY, Issue 18 2008Maureen A. McCall In the most simplistic view, the retinal circuit can be divided into vertical excitatory pathways that use glutamate as their neurotransmitter and lateral inhibitory pathways in the outer and inner synaptic layers that modulate excitation via glycine and GABA. Within the vertical excitatory pathways, the visual signal is initiated in the rod, cone or both photoreceptors, depending on the adaptation state of the retina. This signal is transmitted to the rest of the retina through the bipolar cells, which can be subdivided based on: the photoreceptor that provides their input, their dendritic and axonal morphology, and the polarity of their response evoked by a luminance increment, e.g. depolarizing or hyperpolarizing responses. The polarity of this response is controlled by the type of glutamatergic postsynaptic receptor that is expressed on their dendritic terminals. Hyperpolarizing bipolar cells express AMPA/kainate receptors, whereas depolarizing bipolar cells (DBCs) express the metabotropic glutamate receptor 6 (Grm6). The electroretinogram (ERG) is a non-invasive method used to assess overall retinal function. The initiation of the visual signal in the photoreceptors is reflected in the ERG a-wave and the ensuing depolarization of DBCs in the b-wave. When there is failure of signal transmission from photoreceptors to DBCs or signalling within DBCs, the ERG a-wave is present, while the b-wave is absent or significantly reduced. This ERG phenotype has been found in the human population and is referred to as congenital stationary night blindness. Until recently, it had been assumed that the absence of a b-wave was indicative of a lack of signalling through the On pathway, leaving the Off pathway unaffected. Here we review recent findings that demonstrate that many mouse mutants share a no b-wave ERG phenotype but their retinal morphology and RGC responses differ significantly, suggesting very different effects of the underlying mutations on output from the DBCs to the rest of the retinal circuit. [source] Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fractionARTHRITIS & RHEUMATISM, Issue 1 2009Rebecca L. Rudominer Objective Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with premature atherosclerosis, vascular stiffening, and heart failure. This study was undertaken to investigate whether RA is associated with underlying structural and functional abnormalities of the left ventricle (LV). Methods Eighty-nine RA patients without clinical cardiovascular disease and 89 healthy matched controls underwent echocardiography, carotid ultrasonography, and radial tonometry to measure arterial stiffness. RA patients and controls were similar in body size, hypertension and diabetes status, and cholesterol level. Results LV diastolic diameter (4.92 cm versus 4.64 cm; P < 0.001), mass (136.9 gm versus 121.7 gm; P = 0.004 or 36.5 versus 32.9 gm/m2.7; P = 0.01), ejection fraction (71% versus 67%; P < 0.001), and prevalence of LV hypertrophy (18% versus 6.7%; P = 0.023) were all higher among RA patients versus controls. In multivariate analysis, presence of RA was an independent correlate of LV mass (P = 0.004). Furthermore, RA was independently associated with presence of LV hypertrophy (odds ratio 4.14 [95% confidence interval 1.24, 13.80], P = 0.021). Among RA patients, age at diagnosis and disease duration were independently related to LV mass. RA patients with LV hypertrophy were older and had higher systolic pressure, damage index scores, C-reactive protein levels, homocysteine levels, and arterial stiffness compared with those without LV hypertrophy. Conclusion The present results demonstrate that RA is associated with increased LV mass. Disease duration is independently related to increased LV mass, suggesting a pathophysiologic link between chronic inflammation and LV hypertrophy. In contrast, LV systolic function is preserved in RA patients, indicating that systolic dysfunction is not an intrinsic feature of RA. [source] Role of videofluorography in assessing functional abnormalities in patients of head and neck cancer treated with chemoradiotherapyASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 4 2009Punita LAL Abstract Aim: The major toxicity following treatment for head neck cancer is swallowing dysfunction which can be easily assessed by videofluorography (VFG), allowing documentation of the site and extent of abnormality thereby facilitating directed management. Methods: Between October 2003 and January 2007, 56 patients with locally advanced head and neck cancer were treated by an accelerated radiotherapy schedule with concurrent weekly cisplatin chemotherapy. Three months following treatment, these patients were locally disease free clinically, but complained of varying degrees of dysphagia and were subjected to a VFG evaluation. Results: This group comprised 52 men and four women with a median age of 56 years. The primary site distribution was: oral cavity (9), oropharynx (22), larynx (19), hypopharynx (5) and unknown primary (1). Swallowing function abnormalities in the form of structural displacement and temporal delays were documented and recorded as weakness of the tongue musculature (n = 6), palatal kink (n = 8), premature leak into the oropharynx (n = 20), impaired hyoid elevation (n = 23), impaired epiglottic tilt (n = 26), unilateral pharyngeal wall impairment (n = 16), residuum in vallecula or pyriform fossa (n = 30), aspiration in trachea (n = 29) and loss of nasopharyngeal seal (n = 7). Multiple abnormalities of different sub-sites were seen in each patient. Conclusion: VFG can document dysmotility disorders of upper aero-digestive tract like dysfunction of the base of tongue, larynx and pharyngeal musculature leading to stasis of the bolus and vallecular residuum, epiglottis dysmotility resulting in silent aspirations, and inadequate nasopharyngeal seal leading to nasal regurgitation. A clinical correlation alongwith quantification of VFG findings is required. [source] Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunctionBIPOLAR DISORDERS, Issue 1 2009Amanda R Bolbecker Objectives:, Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. Methods:, Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. Results:, Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. Conclusions:, These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness. [source] Stroop performance in bipolar disorder: further evidence for abnormalities in the ventral prefrontal cortexBIPOLAR DISORDERS, Issue 1 2006Dina M Kronhaus Objectives:, Bipolar patients are impaired in Stroop task performance, a measure of selective attention. Structural and functional abnormalities in task-associated regions, in particular the prefrontal cortex (PFC), have been reported in this population. We aimed to examine the relationship between functional abnormalities, impaired task performance and the severity of depressive symptoms in bipolar patients. Methods:, Remitted bipolar patients (n = 10; all medicated), either euthymic or with subsyndromal depression, and age-matched control subjects (n = 11) viewed 10 alternating blocks of incongruent Stroop and control stimuli, naming the colour of the ink. Neural response was measured using functional magnetic resonance imaging. We computed between-group differences in neural response and within-group correlations with mood and anxiety. Results:, There were no significant between-group differences in task performance. During the Stroop condition, controls demonstrated greater activation of visual and dorsolateral and ventrolateral prefrontal cortical areas; bipolar patients demonstrated relative deactivation within orbital and medial prefrontal cortices. Depression scores showed a trend towards a negative correlation with the magnitude of orbitofrontal cortex deactivation in bipolar patients, whereas state anxiety correlated positively with activation of dorsolateral PFC and precuneus in controls. Conclusions:, Our findings confirm previous reports of decreased ventral prefrontal activity during Stroop task performance in bipolar patients, and suggest a possible negative correlation between this and depression severity in bipolar patients. These findings further highlight the ventromedial PFC as a potential candidate for illness related dysfunction in bipolar disorder. [source] Lower oesophageal sphincter dysfunction is part of the functional abnormality in epiphrenic diverticulumBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2009X. B. D'Journo Background: The pathophysiology and management of epiphrenic diverticula remain controversial. This study investigated the underlying functional abnormalities and long-term results of surgical treatment. Methods: Patients with symptoms and epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV fundoplication were reviewed retrospectively. They were assessed before and after surgery by radiology, functional testing and endoscopy, and compared with a group of 40 normal volunteers. Results: The study included 23 consecutive symptomatic patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower oesophageal sphincter (LOS) incoordination was considered the most constant functional abnormality (P < 0·001). After operation oesophageal diameter increased, contraction pressures decreased and peristalsis was reduced. LOS resting and gradient pressures decreased (P = 0·001). Despite unchanged acid exposure values, endoscopy revealed increased mucosal damage after operation (P = 0·003). New columnar-lined metaplasia was documented in eight patients (P = 0·013). Symptoms had decreased after a median of 61 months (P = 0·001). Conclusion: Epiphrenic diverticulum was associated with spastic dysfunction and LOS abnormalities. A long myotomy including the LOS relieved functional obstruction and symptoms, but partial fundoplication did not prevent reflux damage. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 6 2001G. Westberg Background: The association between malignant midgut carcinoid tumours and right-sided cardiac lesions is well known, but the pathogenetic link between tumour secretion and valvular disease is still obscure. The purpose of this investigation was to describe the morphological and functional changes of valvular heart disease in a large patient series and to correlate these findings with hormonal secretion and prognosis. Methods: Of 64 consecutive patients with the midgut carcinoid syndrome followed between 1985 and 1998, valvular heart disease was evaluated in 52 patients by two-dimensional echocardiography, Doppler estimation of valvular regurgitation and flow profiles. A majority was also evaluated with exercise electrocardiography and spirometry. Results: Structural and functional abnormalities of the tricuspid valve were found in 65 per cent of patients, while only 19 per cent had pulmonary valve regurgitation. Long-term survival was related to excessive urinary excretion of 5,hydroxyindole acetic acid of over 500 µmol in 24 h, but the main predictor of prognosis was the presence of severe structural and functional abnormalities of the tricuspid valve. Although advanced tricuspid abnormalities were prevalent in this series, only one patient died from right ventricular heart failure. Conclusion: Tricuspid valvular disease is a common manifestation of the midgut carcinoid syndrome and advanced changes are associated with poor long-term survival. Active surgical and medical therapy of the tumour disease reduced the hormonal secretion and, combined with cardiological surveillance, made right ventricular heart failure a rare cause of death in these patients. © 2001 British Journal of Surgery Society Ltd [source] A ventral prefrontal-amygdala neural system in bipolar disorder: a view from neuroimaging researchACTA NEUROPSYCHIATRICA, Issue 5 2009Fay Y. Womer In the past decade, neuroimaging research has identified key components in the neural system that underlies bipolar disorder (BD). The ventral prefrontal cortex (VPFC) and amygdala are highly interconnected structures that jointly play a central role in emotional regulation. Numerous research groups have reported prominent structural and functional abnormalities within the VPFC and amygdala supporting their essential role in a neural system underlying the emotional dysregulation that is a core feature of BD. Findings in BD also include those in brain regions interconnected with the VPFC and amygdala, including the ventral striatum, hippocampus and the cerebellum. Abnormalities in these regions may contribute to symptoms that reflect disruption in functions sub-served by these structures, including motivational, mnemonic and psychomotor functions. This article will first review leads from behavioural neurology that implicated these neural system abnormalities in BD. It will then review findings from structural and functional imaging studies to support the presence of abnormalities within these neural system components in BD. It will also review new findings from studies using diffusion tensor imaging (DTI) that provide increasing evidence of abnormalities in the connections between these neural system components in BD. Emerging data supporting differences in this neural system during adolescence, as well as potential beneficial effects of treatment on structure and function will also be presented. Finally, the article will discuss the implications for future investigations, including those for early identification and treatment of BD. [source] 2135: Influence of Hsp90 and HDAC inhibition and tubulin acetylation on perinuclear protein aggregation in human retinal pigment epithelial cellsACTA OPHTHALMOLOGICA, Issue 2010K KAARNIRANTA Purpose Retinal pigment epithelial (RPE) cells are continually exposed to oxidative stress that contributes to protein misfolding, aggregation and functional abnormalities during aging. The protein aggregates formed at the cell periphery are delivered along the microtubulus network by dynein dependent retrograde trafficking to a juxtanuclear location. Methods Cellular organelles were analysed by transmission electron microscopy of ARPE-19 cells exposed 5 µM MG-132, 0.25 µM geldanamycin (GA), 1 µM trichostatin A (TSA), 1 µM taxol (TAX) or 5 µM nocodazole (NOC) for 24 hours. In addition, the cells were treated simultaneously with GA or TSA or TAX or NOC and MG-132 up to 24 hours. Ubiquitin, Hsp90, Hsp70, acetylated tubulin and Hsc70 protein levels were analyzed by western blotting. Results Hsp90 inhibition by geldanamycin can effectively suppress proteasome inhibitor, MG-132 ,induced protein aggregation in a way that is an independent of HDAC inhibition, or the tubulin acetylation levels in ARPE-19 cells. However, the tubulin acetylation and polymerization state affects the localization of the proteasome-inhibitor ,induced aggregation. Conclusion Hsp90 inhibition is effectively related to regulation of protein aggregation that is independent of HDAC inhibition or tubulin acetylation levels in the RPE cells. Our findings open new perspectives for understanding the pathogenesis of protein aggregation in retinal cells and can be useful for the development of therapeutic treatments to prevent retinal cell deterioration. [source] Multi-dimensional phenotyping: towards a new taxonomy for airway diseaseCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2005A. J. Wardlaw Summary All the real knowledge which we possess, depends on methods by which we distinguish the similar from the dissimilar. The greater the number of natural distinctions this method comprehends the clearer becomes our idea of things. The more numerous the objects which employ our attention the more difficult it becomes to form such a method and the more necessary. [1]. Classification is a fundamental part of medicine. Diseases are often categorized according to pre-20th century descriptions and concepts of disease based on symptoms, signs and functional abnormalities rather than on underlying pathogenesis. Where the aetiology of disease has been revealed (for example in the infectious diseases) a more precise classification has become possible, but in the chronic inflammatory diseases, and in the inflammatory airway diseases in particular, where pathogenesis has been stubbornly difficult to elucidate, we still use broad descriptive terms such as asthma and chronic obstructive pulmonary disease, which defy precise definition because they encompass a wide spectrum of presentations and physiological and cellular abnormalities. It is our contention that these broad-brush terms have outlived their usefulness and that we should be looking to create a new taxonomy of airway disease,a taxonomy that more closely reflects the spectrum of phenotypes that are encompassed within the term airway inflammatory diseases, and that gives full recognition to late 20th and 21st century insights into the disordered physiology and cell biology that characterizes these conditions in the expectation that these will map more closely to both aetiology and response to treatment. Development of this taxonomy will require a much more complete and sophisticated correlation of the many variables that make up a condition than has been usual to employ in an approach that encompasses multi-dimensional phenotyping and uses complex statistical tools such as cluster analysis. [source] Attenuated prefrontal activation during a verbal fluency task in remitted major depressionPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 3 2009Go Okada md The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression. [source] Influence of high dietary sodium intake on the functional subtypes of ,1 -adrenoceptors in the renal cortical vasculature of Wistar,Kyoto ratsAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1-2 2009R. N. Kazi Summary 1,Increased renal vascular resistance is one renal functional abnormality that contributes to hypertension, and ,1 -adrenoceptors play a pivotal role in modulating this renal vascular resistance. This study investigates the functional contribution of ,1 -adrenoceptor subtypes in the renal cortical vasculature of Wistar,Kyoto rats on a normal sodium diet (WKYNNa) compared with those given saline to drink for 6 weeks (WKYHNa). 2,The renal cortical vascular responses to the adrenergic agonists noradrenaline (NA), methoxamine (ME) and phenylephrine (PE) were measured in WKYHNa and WKYNNa rats either in the absence (the control phase) or presence of chloroethylclonidine (CEC), an ,1B -adrenoceptor antagonist, 5-methylurapidil (5-MeU), an ,1A antagonist, or BMY7378, an ,1D antagonist. 3,Results showed a greater renal cortical vascular sensitivity to NA, PE and ME in the WKYHNa compared with WKYNNa rats (P < 0.05). Moreover, 5-MeU and BMY7378 attenuated adrenergically induced renal cortical vasoconstriction in WKYHNa and WKYNNa rats; this response was largely blunted in CEC-treated WKYHNa rats (all P < 0.05) but not in CEC-treated WKYNNa rats. 4,The data suggest that irrespective of dietary sodium content, in Wistar,Kyoto rats ,1A - and ,1D -subtypes are the major ,1 -adrenoceptors in renal cortical vasculature; however, there appears to be a functional involvement of ,1B -adrenoceptors in the WKYHNa rats. [source] Lower oesophageal sphincter dysfunction is part of the functional abnormality in epiphrenic diverticulumBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 8 2009X. B. D'Journo Background: The pathophysiology and management of epiphrenic diverticula remain controversial. This study investigated the underlying functional abnormalities and long-term results of surgical treatment. Methods: Patients with symptoms and epiphrenic diverticula who had undergone long myotomy and Belsey Mark IV fundoplication were reviewed retrospectively. They were assessed before and after surgery by radiology, functional testing and endoscopy, and compared with a group of 40 normal volunteers. Results: The study included 23 consecutive symptomatic patients who had surgery, 20 of whom had oesophageal spastic disorders. Lower oesophageal sphincter (LOS) incoordination was considered the most constant functional abnormality (P < 0·001). After operation oesophageal diameter increased, contraction pressures decreased and peristalsis was reduced. LOS resting and gradient pressures decreased (P = 0·001). Despite unchanged acid exposure values, endoscopy revealed increased mucosal damage after operation (P = 0·003). New columnar-lined metaplasia was documented in eight patients (P = 0·013). Symptoms had decreased after a median of 61 months (P = 0·001). Conclusion: Epiphrenic diverticulum was associated with spastic dysfunction and LOS abnormalities. A long myotomy including the LOS relieved functional obstruction and symptoms, but partial fundoplication did not prevent reflux damage. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Short wavelength automated perimetryACTA OPHTHALMOLOGICA, Issue 6 2001John M. Wild ABSTRACT. Short Wavelength Automated Perimetry (SWAP) utilizes a blue stimulus to preferentially stimulate the blue cones and a high luminance yellow background to adapt the green and red cones and to saturate, simultaneously, the activity of the rods. This review describes the theoretical aspects of SWAP, highlights current limitations associated with the technique and discusses potential clinical applications. Compared to white-on-white (W-W) perimetry, SWAP is limited clinically by: greater variability associated with the estimation of threshold, ocular media absorption, increased examination duration and an additional learning effect. Comparative studies of SWAP and W-W perimetry have generally been undertaken on small cohorts of patients. The conclusions are frequently unconvincing due to limitations for SWAP in the delineation of abnormality and of progressive field loss. SWAP is almost certainly able to identify glaucomatous visual field loss in advance of that by W-W perimetry although the incidence of progressive field loss is similar between the two techniques. Increasing evidence suggests that functional abnormality with SWAP is preceded by structural abnormality of the optic nerve head and/or the retinal nerve fibre layer. SWAP appears to be beneficial in the detection of diabetic macular oedema and possibly in some neuro-ophthalmic disorders. 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