Home About us Contact
|
Home About us Contact | ||
|
|
||
Functional Deficits (functional + deficit)
Selected AbstractsCorrelation of anatomy and function in medulla oblongata infarctionEUROPEAN JOURNAL OF NEUROLOGY, Issue 2 2009C. Eggers Background:, A presentation of all aspects of the dorsolateral medulla oblongata syndrome is clinically very rare to find. In most cases patients present with fragmentary symptoms, e.g. ipsilateral axial lateropulsion, nystagmus, dysarthria, dysphagia or hemiataxia. However, the clinical presentation and lesion anatomy at the level of the medulla oblongata is still unsatisfactory. The aim of this study was to correlate the functional deficit with structural MRI-data. Methods:, We included thirteen patients (eight male, five female, mean age 65.5) with medulla oblongata infarction with clinically predominant ipsilateral axial lateropulsion and correlated clinical with structural deficits. Results:, Magnetic resonance imaging lesion mapping demonstrated ipsilateral axial lateropulsion to result from lesions of the spinocerebellar tract, the inferior cerebellar peduncle or the inferior vestibular nucleus. Nystagmus was associated with lesions of the inferior vestibular nucleus, dissociated sensory loss with the spinothalamic tract and hemiataxia with the spinocerebellar tract. Conclusions:, Correlating dysfunction and lesion anatomy is a promising approach to enhance our knowledge on medulla oblongata topography. [source] The symptomatic treatment of multiple system atrophyEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2002C. Colosimo Multiple system atrophy (MSA) is a neurodegenerative disease of undetermined aetiology that occurs sporadically and manifests itself as a combination of parkinsonian, autonomic, cerebellar and pyramidal signs. Despite the lack of any effective therapy to reverse this condition, some of the symptoms may be, at least temporarily, improved with adequate symptomatic therapies. Medical treatment is largely aimed at mitigating the parkinsonian and autonomic features. The therapeutic results of levodopa therapy in cases of MSA are difficult to interpret because of their variability. Nevertheless, the statement that patients with MSA are non or poorly levodopa-responsive is misleading. Clinical and pathologically proven series document about 40,60% levodopa efficacy in patients with MSA presenting with predominant parkinsonian features. Unfortunately, other antiparkinsonian compounds (dopamine agonists, amantadine) are not more effective than levodopa. Orthostatic hypotension (OH) can be suspected from the patient's history and subsequently documented in the clinic by measuring lying and standing blood pressure. The diagnosis ideally should be confirmed in the laboratory with additional tests to determine the cause and evaluate the functional deficit, so as to aid treatment. A variety of pharmacological agents with different mechanisms of action have been used in MSA to reduce OH when this is symptomatic. OH can also be alleviated by avoiding aggravating factors, such as the effects of food, micturition, exposure to a warm environment and physiological diurnal changes and by using other non-pharmacological strategies. The treatment of the very common genito-urinary symptoms (incontinence, retention, impotence) should also be considered in order to improve the quality of life of these patients. [source] Total joint arthroplasty in haemophiliaHAEMOPHILIA, Issue 5 2000Beeton In severely affected haemophilic patients arthropathy is a common problem which can lead to considerable pain and functional deficit. Surgical management, including total joint arthroplasty, can be undertaken if conservative management fails. A search of the literature showed that a number of studies describing the use of total knee arthroplasty (TKA) and total hip arthroplasty (THA) in haemophilia have been published, whereas shoulder, elbow and ankle arthroplasties are confined to case reports. This paper reviews the functional outcome of arthroplasty in the different joints, the postoperative and long-term complications, and the impact of HIV. Although complications are commonly described and the surgery is technically demanding, the results suggest that arthroplasty, particularly of the hip and knee, can be a valuable option in the management of severe haemophilic arthropathy. [source] Resting state sensorimotor functional connectivity in multiple sclerosis inversely correlates with transcallosal motor pathway transverse diffusivityHUMAN BRAIN MAPPING, Issue 7 2008Mark J. Lowe Abstract Recent studies indicate that functional connectivity using low-frequency BOLD fluctuations (LFBFs) is reduced between the bilateral primary sensorimotor regions in multiple sclerosis. In addition, it has been shown that pathway-dependent measures of the transverse diffusivity of water in white matter correlate with related clinical measures of functional deficit in multiple sclerosis. Taken together, these methods suggest that MRI methods can be used to probe both functional connectivity and anatomic connectivity in subjects with known white matter impairment. We report the results of a study comparing anatomic connectivity of the transcallosal motor pathway, as measured with diffusion tensor imaging (DTI) and functional connectivity of the bilateral primary sensorimotor cortices (SMC), as measured with LFBFs in the resting state. High angular resolution diffusion imaging was combined with functional MRI to define the transcallosal white matter pathway connecting the bilateral primary SMC. Maps were generated from the probabilistic tracking employed and these maps were used to calculate the mean pathway diffusion measures fractional anisotropy ,FA,, mean diffusivity ,MD,, longitudinal diffusivity ,,1,, and transverse diffusivity ,,2,. These were compared with LFBF-based functional connectivity measures (Fc) obtained at rest in a cohort of 11 multiple sclerosis patients and ,10 age- and gender-matched control subjects. The correlation between ,FA, and Fc for MS patients was r = ,0.63, P < 0.04. The correlation between all subjects ,,2, and Fc was r = 0.42, P < 0.05. The correlation between all subjects ,,2, and Fc was r = ,0.50, P < 0.02. None of the control subject correlations were significant, nor were ,FA,, ,,1,, or ,MD, significantly correlated with Fc for MS patients. This constitutes the first in vivo observation of a correlation between measures of anatomic connectivity and functional connectivity using spontaneous LFBFs. Hum Brain Mapp, 2008. © 2008 Wiley-Liss, Inc. [source] Functional correlates of lower cognitive test scores in essential tremor,MOVEMENT DISORDERS, Issue 4 2010Elan D. Louis MD Abstract Although motor features have been the defining element of essential tremor (ET), lower neurocognitive test scores are increasingly being recognized. However, the clinical correlates, if any, of these lower test scores remain largely unexplored. The aim of this study was to determine whether cognitive test scores in ET have any functional correlates. The Modified Mini Mental Status Examination (MMSE), Katz Activities of Daily Living (ADL) scale and Lawton Instrumental (I) ADL scale were administered to 95 cases. The Katz ADL score (rho = 0.26, P = 0.01) and Lawton IADL score (rho = 0.32, P = 0.001) were correlated with MMSE scores, such that poorer cognitive performance indicated greater dysfunction. Furthermore, cognitive test scores were a better predictor of functional disability than was tremor severity. Poorer cognitive performance in ET was associated with greater functional deficit. Cognition should enter the clinical dialog with ET patients as an issue of clinical significance. © 2010 Movement Disorder Society [source] Functional impairment after latissimus dorsi flapANZ JOURNAL OF SURGERY, Issue 1-2 2009Cherry E. Koh Abstract Background:, Available published reports suggest that loss of latissimus dorsi muscle following latissimus myocutaneous flap does not lead to functional impairment. However, significant functional impairment has been observed in clinical practice, prompting this study to evaluate the functional deficit in patients who had undergone reconstruction using latissimus dorsi muscle. Methods:, A retrospective review was undertaken between 1998 and 2003. Patients were identified from the audit of the plastic surgery unit at St Vincent's Hospital and recruited by direct telephone contact. They were assessed using the Disability of Arm, Shoulder and Hand questionnaire. Results:, There were 25 participants. Eighteen completed their questionnaires. Six of 18 patients reported scores of 30 or more, which corresponded to a global moderate functional deficit. These patients were severely limited in their ability to carry out housework. Major postoperative complications were associated with high Disability of Arm, Shoulder and Hand scores (P = 0.028). Three of five patients involved with sports reported impaired performance in sports. The subgroup of four patients who underwent bilateral latissimus dorsi flaps also experienced significant morbidity with all four reporting moderate to severe impairment in their ability to return to gardening and/or sports. Conclusion:, Patients undergoing this procedure should be fully informed of potential sequelae. Athletic patients and patients undergoing bilateral latissimus dorsi flaps should also be warned of possible reduced performance in sports. Alternatively, perforator cutaneous flaps, which preserve the latissimus muscle, should be chosen when feasible. [source] HS08 CONGENITAL HAND: THE DEFORMITY-DEFICIENCY INDEXANZ JOURNAL OF SURGERY, Issue 2007L. C. Teoh Congenital hand is a complex and vast subject therefore classification is very necessary for the purpose of teaching, communication and guide treatment. The first comprehensive and yet user friendly classification was proposed by Swanson et al. in 1976. This classification based on etiopathogenic is popularly known as the ,IFSSH 7 groups classification'. (I) Failure of formation: transverse or longitudinal (II) Failure of differentiation (III) Polydactyly (IV) Overgrowth (V) Undergrowth (VI) Amniotic band syndrome (VII) Generalized skeletal syndromes. However this classification was found not able to satisfactorily classify 20,30% of cases. Other classifications based on genetic defects, teratogenic sequence and syndromics were being introduced previously and continue to be used parallel with the IFSSH classification. Furthermore the classification continue to be besieged by multiple morphological types of deformity in a same hand. Ogino introduced the JSSH expanded classification to address some of the deficiencies of the IFSSH classification. For a beginner in treating congenital hand, it is indeed daunting, as the variations in morphology, the degree of severity and functional deficit even in the same diagnosis can be very different. It is usual to find further sub classifications. For the purpose of guiding treatment, I propose the concept of deformity/ deficiency index. Group I) The imbalance/ small in size II) Extra digits III) Mal positioned/ Mal-aligned IV) Poor/ No function V) Total absent. The residual functional decreases from group I to V. And similarly the reconstruction becomes complex and difficult. [source] Postmarketing surveillance for human teratogenicity: A model approach,BIRTH DEFECTS RESEARCH, Issue 5 2001Christina D. Chambers Background Most congenital defects associated with prenatal exposures are notable for a pattern of major and minor malformations, rather than for a single major malformation. Thus, traditional epidemiological methods are not universally effective in identifying new teratogens. The purpose of this report is to outline a complementary approach that can be used in addition to other more established methods to provide the most comprehensive evaluation of prenatal exposures with respect to teratogenicity. Methods We describe a multicenter prospective cohort study design involving dysmorphological assessment of liveborn infants. This design uses the Organization of Teratology Information Services, a North American network of information providers who also collaborate for research purposes. Procedures for subject selection, methods for data collection, standard criteria for outcome classification, and the approach to analysis are detailed. Results The focused cohort study design allows for evaluation of a spectrum of adverse pregnancy outcomes ranging from spontaneous abortion to functional deficit. While sample sizes are typically inadequate to identify increased risks for single major malformations, the use of dysmorphological examinations to classify structural anomalies provides the unique advantage of screening for a pattern of malformation among exposed infants. Conclusions As the known human teratogens are generally associated with patterns of structural defects, it is only when studies of this type are used in combination with more traditional methods that we can achieve an acceptable level of confidence regarding the risk or safety of specific exposures during pregnancy. Teratology 64:252,261, 2001. © 2001 Wiley-Liss, Inc. [source] The multifocal electroretinogram (mfERG) in the pigACTA OPHTHALMOLOGICA, Issue 4 2007Maria Voss Kyhn Abstract. Purpose:, To establish a method allowing multifocal electroretinography (mfERG) recording with simultaneous fundus monitoring on anaesthetized pigs. In addition we characterize the peaks of the porcine mfERG trace, and compare the visual streak area with the optic nerve head, a known non-response area. Finally we illustrate the feasibility of the method by performing mfERG after an induced laser burn in the visual streak. Methods:, Fifteen pigs underwent mfERG recordings at baseline, and after 1 and 6 weeks of observation. One pig was evaluated before and after retinal diode laser treatment in the visual streak. Results:, The porcine mfERG trace appears similar to the human mfERG trace, and can be described by three peaks named N1, P1 and N2. Significantly faster implicit time was found in the visual streak regarding N1 (P < 0.001) than in areas outside the visual streak. Amplitudes of all three peaks were increased in the visual streak (P < 0.005). The laser-treated area was characterized by a response similar to what is found at the location of the optic nerve head. Conclusion:, Porcine mfERG is similar in appearance to the human response and can be described by the same three peaks. Significantly higher amplitudes of all three peaks are found in the visual streak when compared to the optic nerve head and inferior retina. We have detected the functional deficit caused by a laser burn at the size of 3 × 3 mm. [source] Conservation surgery in the management of T1 and T2 oropharyngeal squamous cell carcinoma: the Birmingham UK experienceCLINICAL OTOLARYNGOLOGY, Issue 6 2002J.C. Watkinson The aim of this paper was to evaluate our experience using conservation surgery in the management of T1 and T2 oropharyngeal squamous cell carcinoma. Eighteen patients underwent conservation surgery between 1993 and 2000 and were analysed retrospectively. The mean age was 54 years and the male to female ratio was 8:1. There were 14 tonsil and 4 tongue base tumours and 83% of cases presented with neck nodes, thereby classifying them as having advanced disease (stages 2,4). All patients received postoperative radiotherapy. All patients were followed up to December 2001. The median follow-up time was 3.8 years (minimum was 1.5 years). The 2-year and 5-year survival rates were 100% and 92% respectively. Approximately 66% of patients returned the EORTC and GHQ/12 quality-of-life questionnaires. Of these, seventy-five percent had a high healthy level of general functioning in accordance with the EORTC general health section. These results show that conservation surgery techniques are effective in the treatment of T1 and T2 oropharyngeal squamous carcinoma associated with significant metastatic neck disease. The techniques are well tolerated, produce minimal functional deficit and do not have a negative impact on the patients quality of life in either the immediate postoperative period or up to 4 years post-treatment. [source] Inhibitory deficits in tourette's syndromeDEVELOPMENTAL PSYCHOBIOLOGY, Issue 1 2008Emily R. Stern Abstract A developmental approach to the study of psychopathology can broaden understanding of a wide variety of complex psychological disorders. This article reviews research on Tourette's syndrome (TS), a developmental disorder characterized by unwanted motor and vocal tics. Over the past decade, knowledge of the neurobiology and pathophysiology of TS has progressed rapidly. The application of brain imaging techniques, primarily magnetic resonance imaging, to the study of Tourette's has increased knowledge of structural and functional deficits in brain areas associated with behavioral and psychological disturbances in the disorder. By reviewing some of this work, we will describe one way in which knowledge of brain function in TS has both informed and been informed by a developmental science approach. In particular, we will consider the extent to which the cognitive and emotional development of persons with TS may be affected by specific neurobiological characteristics of the disorder. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 50: 9,18, 2008. [source] Recreational ecstasy use and the neurotoxic potential of MDMA: current status of the controversy and methodological issuesDRUG AND ALCOHOL REVIEW, Issue 3 2006MICHAEL LYVERS Abstract The controversy over possible MDMA-induced serotonergic neurotoxicity in human recreational ecstasy users is examined critically in light of recent research findings. Although the designs of such studies have improved considerably since the 1990s, the evidence to date remains equivocal for a number of reasons, including (1) inconsistent findings on the existence and reversibility of persistent ecstasy-related serotonergic and cognitive deficits; (2) lack of clear association between changes in brain imaging measures and functional deficits attributed to MDMA-induced neurotoxicity; (3) the contribution of concomitant cannabis or other drug use to both brain imaging abnormalities and cognitive deficits; (4) methodological shortcomings such as failure to adequately match samples of ecstasy users and controls; (5) the questionable relevance of animal models of MDMA-induced neurotoxicity to typical human patterns of ecstasy use; and (6) the potential role of inherent pre-drug deficits in serotonergic systems, impulse control and executive cognitive function that may predispose to excessive use of drugs including ecstasy. Given the retrospective nature of nearly all studies of ecstasy users to date, the controversy over whether MDMA has ever caused neurotoxicity or cognitive deficit in human ecstasy users is likely to continue for some time without resolution. [source] Comparison of Effect of Aerobic Cycle Training and Progressive Resistance Training on Walking Ability After Stroke: A Randomized Sham Exercise,Controlled StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2008Mi-Joung Lee PhD OBJECTIVES: To determine whether changes in strength or cardiorespiratory fitness after exercise training improve walking ability in individuals who have had a stroke. DESIGN: A sham exercise-controlled, randomized two-by-two factorial design, in which the two factors investigated were cycle training (AEROBIC) and resistance training (STRENGTH). SETTING: University exercise laboratory. PARTICIPANTS: Fifty-two individuals with a history of stroke (aged 63±9; time since stroke, 57±54 months). INTERVENTION: Participants undertook 30 exercise sessions over 10 to 12 weeks. Depending on group allocation, individuals underwent aerobic cycling plus sham progressive resistance training (PRT) (n=13), sham cycling plus PRT (n=13), aerobic cycling plus PRT (n=14), or sham cycling plus sham PRT (n=12). MEASUREMENTS: Primary outcomes were 6-minute walk distance, habitual and fast gait velocities, and stair climbing power. Secondary outcomes included measures of cardiorespiratory fitness; muscle strength, power, and endurance; and psychosocial attributes. RESULTS: Neither AEROBIC nor STRENGTH improved walking distance or gait velocity significantly more than sham exercise, although STRENGTH significantly improved participants' stair climbing power by 17% (P=.009), as well as their muscle strength, power, and endurance; cycling peak power output; and self-efficacy. Conversely, AEROBIC improved indicators of cardiorespiratory fitness only. Cycling plus PRT produced larger effects than either single modality for mobility and impairment outcomes. CONCLUSION: Single-modality exercises targeted at existing impairments do not optimally address the functional deficits of walking but do ameliorate the underlying impairments. The underlying cardiovascular and musculoskeletal impairments are significantly modifiable years after stroke with targeted robust exercise. [source] Attention Deficit Hyperactivity Disorder: Current Concepts and Underlying MechanismsJOURNAL OF CHILD AND ADOLESCENT PSYCHIATRIC NURSING, Issue 3 2000Brenda J. Wagner PhD TOPIC. Neuropsychological concentration of attention deficit hyperactivity disorder (ADHD). PURPOSE. Survey of current understanding of underlying neural systems and pathways involved in ADHD and the relationship to specific behavioral patterns. SOURCES. Literature review, author's experience in neuropsychological assessment and clinical treatment. CONCLUSIONS. Clinicians will be able to specify treat men t interventions designed to compensate for specific behavioral patterns and functional deficits. [source] Subcortical lesions after transient thread occlusion in the rat: T2 -weighted magnetic resonance imaging findings without corresponding sensorimotor deficitsJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2005Susanne Wegener MD Abstract Purpose To investigate infarct evolution and functional consequences of exclusive subcortical or cortico-subcortical strokes, transient middle cerebral artery occlusion (MCAO) was conducted in Wistar rats. Materials and Methods MCAO was induced in male Wistar rats (260,300 g) for 60 minutes. Lesion volumes and absolute T2 times on magnetic resonance imaging (MRI) were assessed 1 and 14 days after MCAO using a 4.7-T MRI animal scanner in conjunction with functional testing (adhesive tape removal, cylinder test, and ledged beam walking). Results Functional test scores were not distinguishable between sham-operated animals (N = 5) and those with exclusive caudoputaminal infarct (N = 8; group cp), but showed significant deficits in animals with cortico-subcortical infarction (N = 10; group cp+). The cp group had lower absolute T2 times and a more pronounced reduction in T2 lesion volume over time than the subcortical component in the cp+ group. There was no correlation of T2 lesion size or absolute T2 times and functional impairment in either group. Conclusion When judged from functional tests alone, subcortical ischemic lesions may not be diagnosed reliably. Furthermore, T2 -weighted (T2 -w) MRI does not well anticipate functional deficits in primarily striatal lesions. J. Magn. Reson. Imaging 2005;21:340,346. © 2005 Wiley-Liss, Inc. [source] Expression of mutant SOD1G93A in astrocytes induces functional deficits in motoneuron mitochondriaJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Lynsey G. Bilsland Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration resulting in paralysis and eventual death. ALS is regarded as a motoneuron-specific disorder but increasing evidence indicates non-neuronal cells play a significant role in disease pathogenesis. Although the precise aetiology of ALS remains unclear, mutations in the superoxide dismutase (SOD1) gene are known to account for approximately 20% of familial ALS. We examined the influence of SOD1G93A expression in astrocytes on mitochondrial homeostasis in motoneurons in a primary astrocyte : motoneuron co-culture model. SOD1G93A expression in astrocytes induced changes in mitochondrial function of both SOD1G93A and wild-type motoneurons. In the presence of SOD1G93A astrocytes, mitochondrial redox state of both wild-type and SOD1G93A motoneurons was more reduced and mitochondrial membrane potential decreased. While intra-mitochondrial calcium levels [Ca2+]m were elevated in SOD1G93A motoneurons, changes in mitochondrial function did not correlate with [Ca2+]m. Thus, expression of SOD1G93A in astrocytes directly alters mitochondrial function even in embryonic motoneurons, irrespective of genotype. These early deficits in mitochondrial function induced by surrounding astrocytes may increase the vulnerability of motoneurons to other neurotoxic mechanisms involved in ALS pathogenesis. [source] Transient versus prolonged hyperlocomotion following lateral fluid percussion injury in mongolian gerbilsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2006Shihong Li Abstract Posttraumatic hyperactivity is a neurobehavioral symptom commonly seen in patients after traumatic brain injury (TBI). No useful animal model has yet been established for evaluation of this important symptom. We induced either mild (MILD, 0.7,0.9 atm) or moderate (MOD, 1.3,1.6 atm) lateral fluid percussion injury (LFPI) in Mongolian gerbils. Open-field and T-maze tests were used during a 7-day period after the trauma. All animals were perfusion fixed for histopathological examinations. Transient locomotor hyperactivity was found with a peak at 6 hr after injury in the MILD animals, whereas MOD animals showed prolonged and severe hyperlocomotion throughout the 7-day posttrauma period (P < 0.0001). Interestingly, the temporal profile of the posttraumatic hyperactivity was similar to that of the working memory deficit in both injury groups. Histological examination revealed significant neural tissue damages, including cortical necrosis, white matter rarefaction, and neuronal loss in the hippocampus in the ipsilateral hemisphere of the MOD animals, vs. only negligible changes in the MILD animals. Correlation analysis revealed that the volume of white matter lesions was significantly correlated with both posttraumatic hyperactivity (r = 0.591, P < 0.01) and working memory deficit (r = ,0.859, P < 0.0001). Taken together, our findings confirm the successful reproduction of posttraumatic hyperactivity following experimental TBI. The posttraumatic hyperlocomotion probably shared pathomechanisms common to those of cognitive dysfunction caused by LFPI, supporting the speculation from previous studies that some neurobehavioral abnormities intimately correlate with TBI-induced cognitive dysfunction. Histopathologically, significant involvement of white matter damage in the posttraumatic functional deficits was indicated. © 2006 Wiley-Liss, Inc. [source] Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2005Eric Anthony Sribnick Abstract Spinal cord injury (SCI) is a devastating neurologic injury with functional deficits for which the only currently recommended pharmacotherapy is high-dose methylprednisolone, which has limited efficacy. Estrogen is a multiactive steroid that has shown antiinflammatory and antioxidant effects, and estrogen may modulate intracellular Ca2+ and attenuate apoptosis. For this study, male rats were divided into three groups. Sham group animals received a laminectomy at T12. Injured rats received both laminectomy and 40 g · cm force SCI. Estrogen-group rats received 4 mg/kg 17,-estradiol (estrogen) at 15 min and 24 hr post-injury, and vehicle-group rats received equal volumes of dimethyl sulfoxide (vehicle). Animals were sacrificed at 48 hr post-injury, and 1-cm-long segments of the lesion, rostral penumbra, and caudal penumbra were excised. Inflammation was assessed by examining tissue edema, infiltration of macrophages/microglia, and levels of cytosolic and nuclear NF,B and inhibitor of kappa B (I,B,). Myelin integrity was examined using Luxol fast blue staining. When compared to sham, vehicle-treated animals revealed increased tissue edema, increased infiltration of inflammatory cells, decreased cytosolic levels of NF,B and I,B,, increased levels of nuclear NF,B, and increased myelin loss. Treatment of SCI rats with estrogen reduced edema and decreased inflammation and myelin loss in the lesion and penumbral areas, suggesting its potential as a therapeutic agent. Further work needs to be done, however, to elucidate the neuroprotective mechanism of estrogen. © 2005 Wiley-Liss, Inc. [source] Exercise Neuroprotection in a Rat Model of Binge Alcohol ConsumptionALCOHOLISM, Issue 3 2010J. Leigh Leasure Background:, Excessive alcohol intake produces structural and functional deficits in corticolimbic pathways that are thought to underlie cognitive deficits in the alcohol use disorders (AUDs). Animal models of binge alcohol administration support the direct link of high levels of alcohol consumption and neurotoxicity in the hippocampus and surrounding cortex. In contrast, voluntary wheel running enhances hippocampal neurogenesis and generally promotes the health of neurons. Methods:, We investigated whether voluntary exercise prior to binge alcohol exposure could protect against alcohol-induced cell loss. Female Long-Evans rats exercised voluntarily for 14 days before undergoing 4 days of binge alcohol consumption. Brains were harvested immediately after the last dose of alcohol and examined for various histological markers of neurodegeneration, including both cell death (FluoroJade B) and cell birth (Ki67) markers. Results:, Rats that exercised prior to binge exposure were significantly less behaviorally intoxicated, which was not a result of enhanced hepatic metabolism. Rats that exercised prior to binge alcohol consumption had reduced loss of dentate gyrus granule cells and fewer FluoroJade B positive cells in the dentate gyrus and associated entorhinal-perirhinal cortex compared to nonexercisers. However, exercise did not protect against cell death in the piriform cortex nor protect against alcohol-induced decreases in cell proliferation, evidenced by a similar alcohol-induced reduction in Ki67 labeled cells between exercise and sedentary rats. Conclusions:, We conclude that exercise can reduce behavioral sensitivity to ethanol intoxication and protect vulnerable brain areas from alcohol-induced cell death. Exercise neuroprotection of alcohol-induced brain damage has important implications in understanding the neurobiology of the AUDs as well as in developing novel treatment strategies. [source] Rehabilitation of surgical cancer patients at University of Texas M. D. Anderson Cancer CenterJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2007Rajesh Yadav MD Abstract With early detection and treatment, survival rates for many types of cancer have improved. Long term survivors have number of issues, which can include functional deficits, pain, fatigue, lymphedema and altered bowel and bladder function. Simple activities such as mobility and the ability to perform self care can be limited. In addition, re-integration into society with activities such as driving, social interaction and return to work are often problematic. The goal of cancer rehabilitation is to improve quality of life by minimizing disability and handicap caused by cancer and associated treatments. Initial rehabilitation interventions usually occur in an inpatient setting as patients often experience a decline in functional status due to cancer progression and or surgical treatment. Rehabilitation interventions reduce the debility and functional deficits and add to the quality of life for cancer patients undergoing surgical treatments. The rehabilitation team can assist not only with acute decline in functional status but also with re-integration back in society. Both general and specific rehabilitation interventions based on diagnoses are reviewed. J. Surg. Oncol. 95:361,369. © 2007 Wiley-Liss, Inc. [source] Dose-Dependent Effects of Prenatal Ethanol Exposure on Synaptic Plasticity and Learning in Mature OffspringALCOHOLISM, Issue 11 2002Daniel D. Savage Background We have observed profound deficits in hippocampal synaptic plasticity and one-trial learning in offspring whose mothers drank moderate quantities of ethanol during pregnancy. In the present study, we examined the question of whether lower maternal blood ethanol concentrations (BECs) could produce functional deficits in offspring. Methods Rat dams consumed either a 2%, 3%, or 5% ethanol liquid diet throughout gestation. Three other groups of dams were pair-fed a 0% ethanol liquid diet, and a seventh group consumed lab chow ad libitum. Adult offspring from each diet group were assigned either to studies of evoked [3H]-D-aspartate (D-ASP) release from hippocampal slices or spatial learning studies using the Morris Water Task. Results Consumption of the 2%, 3%, and 5% ethanol liquid diets produced mean peak maternal BECs of 7, 30 and 83 mg/dL, respectively. Consumption of these ethanol diets had no effect on offspring birthweight, litter size or neonatal mortality. Likewise, evoked D-ASP release from hippocampal slices and performance on a standard version of the Morris Water Task were not affected by prenatal ethanol exposure. By contrast, activity-dependent potentiation of evoked D-ASP release from slices and one-trial learning on a "moving platform" version of the Morris Water Task were markedly reduced in offspring whose mothers consumed the 5% ethanol liquid diet. Intermediate deficits in these two parameters were observed in offspring from the 3% ethanol diet group, whereas offspring from the 2% ethanol diet group were not statistically different than controls. Conclusions We conclude that the threshold for eliciting subtle, yet significant learning deficits in offspring prenatally exposed to ethanol is less than 30 mg/dL. This BEC is roughly equivalent to drinking 1 to 1.5 ounces of ethanol per day. [source] Human neural stem cells genetically modified for brain repair in neurological disordersNEUROPATHOLOGY, Issue 3 2004Seung U. Kim Existence of multipotent neural stem cells (NSC) has been known in developing or adult mammalian CNS, including humans. NSC have the capacity to grow indefinitely and have multipotent potential to differentiate into three major cell types of CNS, neurons, astrocytes and oligodendrocytes. Stable clonal lines of human NSC have recently been generated from the human fetal telencephalon using a retroviral vector encoding v-myc. One of the NSC lines, HB1.F3, carries normal human karyotype of 46XX and has the ability to self-renew, differentiate into cells of neuronal and glial lineages, and integrate into the damaged CNS loci upon transplantation into the brain of animal models of Parkinson disease, HD, stroke and mucopolysaccharidosis. F3 human NSC were genetically engineered to produce L-dihydroxyphenylalanine (L-DOPA) by double transfection with cDNA for tyrosine hydroxylase and guanosine triphosphate cylohydrolase-1, and transplantation of these cells in the brain of Parkinson disease model rats led to L-DOPA production and functional recovery. Proactively transplanted F3 human NSC in rat striatum, supported the survival of host striatal neurons against neuronal injury caused by 3-nitropro-pionic acid in rat model of HD. Intravenously introduced through the tail vein, F3 human NSC were found to migrate into ischemic lesion sites, differentiate into neurons and glial cells, and improve functional deficits in rat stroke models. These results indicate that human NSC should be an ideal vehicle for cell replacement and gene transfer therapy for patients with neurological diseases. In addition to immortalized human NSC, immortalized human bone marrow mesenchymal stem cell lines have been generated from human embryonic bone marrow tissues with retroviral vectors encording v-myc or teromerase gene. These immortalized cell lines of human bone marrow mesenchymal stem cells differentiated into neurons/glial cells, bone, cartilage and adipose tissue when they were grown in selective inducing media. There is further need for investigation into the neurogenic potential of the human bone marrow stem cell lines and their utility in animal models of neurological diseases. [source] Physical sequelae and self-perceived attachment in adult survivors of childhood cancerPSYCHO-ONCOLOGY, Issue 4 2001David Joubert The association between the physical sequelae of childhood cancer and self-reported attachment behavior was investigated in 97 adult survivors. Attachment was assessed using standardized self-report questionnaires. Functional disability and cosmetic sequelae of the cancer and its treatment were evaluated by the attending oncologist using a standardized rating scale. Results suggest that attachment is not significantly associated with physician-rated physical sequelae, but may be related to the time of onset of the functional deficits, independent of the current age or age at diagnosis. Further, survivors with functional sequelae in adulthood describe themselves as more insecure in their relationships in general and more ambivalent in their relationship with their parents. These findings, if replicated, suggest that the duration of the functional deficits as well as the developmental stage of the individual when they began may be important variables which affect the survivor's capacity to develop and maintain intimate relationships that are secure and satisfying. Copyright © 2001 John Wiley & Sons, Ltd. [source] Annotation: The role of prefrontal deficits, low autonomic arousal, and early health factors in the development of antisocial and aggressive behavior in childrenTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 4 2002Adrian Raine Background: This article selectively reviews the biological bases of antisocial and aggressive behavior in children with a focus on low autonomic functioning, prefrontal deficits, and early health factors. Results: Low resting heart rate is thought to be the best-replicated biological correlate of antisocial and aggressive behavior in child and adolescent populations and may reflect reduced noradrenergic functioning and a fearless, stimulation-seeking temperament. Evidence from neuropsychological, neurological, and brain imaging studies converges on the conclusion that prefrontal structural and functional deficits are related to antisocial, aggressive behavior throughout the lifespan. A prefrontal dysfunction theory of antisocial behavior is advanced. This argues that social and executive function demands of late adolescence overload the late developing prefrontal cortex, giving rise to prefrontal dysfunction and a lack of inhibitory control over antisocial, violent behavior that peaks at this age. Birth complications and minor physical anomalies are selectively associated with later violent behavior, especially when combined with adverse psychosocial risk factors for violence. Cigarette smoking during pregnancy may increase the risk for antisocial and violent behavior in later life by disrupting noradrenergic functioning and enhancement of cholinergic receptors that inhibit cardiac functioning. Malnutrition during pregnancy is associated with later antisocial behavior and may be mediated by protein deficiency. Conclusions: It is argued that early health intervention and prevention studies may provide the most effective way of reversing biological deficits that predispose to antisocial and aggressive behavior in children and adults. [source] Aging of the nigrostriatal system in the squirrel monkeyTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2004Alison L. McCormack Abstract Increasing incidence of Parkinson's disease with advancing age suggests that age-related processes predispose the nigrostriatal dopaminergic system to neurodegeneration. Several hypotheses concerning the effects of aging on nigrostriatal neurons were assessed in this study using a non-human primate model. First, we examined the possibility that the total number of dopaminergic neurons decline in the substantia nigra as a function of age. Stereological counting based on both tyrosine hydroxylase immunoreactivity (TH-ir) and neuromelanin (NM) content revealed no difference in cell number between young, middle-aged and old squirrel monkeys. We then determined whether advancing age changed the relative proportion of neurons characterized by 1) TH-ir in the absence of NM, 2) the presence of both TH-ir and NM, or 3) NM without TH-ir. Indeed, a progressive age-related depletion of TH only cells was paralleled by an increase in NM only neurons. The possibility that these changes could underlie a functional impairment of the nigrostriatal system was supported by striatal dopamine measurements showing a decrease in older monkeys. Finally, we tested the hypotheses that aging may enhance cell vulnerability to injury and that different dopaminergic subpopulations display varying degrees of susceptibility. When monkeys were exposed to the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, cell loss was markedly more pronounced in older animals, and the ranking of vulnerability was TH only < TH/NM < NM only cells. The data indicate that, even in the absence of an overall neuronal loss, changes in the characteristics of dopaminergic cells reflect functional deficits and increased vulnerability to injury with age. NM content appears to be an important marker of these age-related effects. J. Comp. Neurol. 471:387,395, 2004. © 2004 Wiley-Liss, Inc. [source] External Beam Radiation Followed by Planned Neck Dissection and Brachytherapy for Base of Tongue Squamous Cell Carcinoma,THE LARYNGOSCOPE, Issue 10 2000David M. Kaylie MD Abstract Background Surgical resection of tongue base cancer can leave the patient with significant functional deficits. Other therapies, such as external beam radiation followed by neck dissection and radiation implants, have shown equal tumor control with good functional outcome. Methods Between March 1991 and July 1999, 12 patients at Oregon Health Sciences University, the Portland Veterans Administration Medical Center and West Virginia University School of Medicine Hospital were treated with external beam radiation followed by neck dissection and Ir192 implants. Two patients had T1 disease, two had T2, five patients had T3 tumors, and three had T4 tumors. Six had N2a necks, three had N2b necks, and three had N2c. Follow-up ranged from 13 months to 8 years. Results After external beam radiation, five patients had complete response and seven had partial response in the neck without complications. One patient underwent a unilateral radical neck dissection, eight had unilateral selective neck dissections involving levels I to IV, and three had dissections involving levels I to III. One of the five patients who had a complete clinical response in the neck had pathologically positive nodes. One patient had a pulmonary embolus that was treated and had no permanent sequelae. There were three complications from brachytherapy. Two patients had soft tissue necrosis at the primary site and one patient had radionecrosis of the mandible. All healed without further therapy. One patient had persistent disease and underwent a partial glossectomy but died of local disease. Distant metastasis developed in two patients. All others show no evidence of disease and are able to eat a normal diet by mouth. Conclusion This combination of therapies should be considered when treating tongue base cancer. [source] Benefit of Feeding Assessment Before Pediatric Airway Reconstruction ,THE LARYNGOSCOPE, Issue 5 2000Jay Paul Willging MD Abstract Objectives/Hypothesis To determine the utility of preoperative feeding assessments in children undergoing airway reconstruction, identifying parameters that correlate with functional deficits in swallowing and postoperative feeding difficulties. Study Design Prospective, sequential enrollment. Methods Two hundred fifty-five patients with structural abnormalities of the upper aerodigestive tract underwent endoscopic swallow studies. Classification of preoperative feeding abilities, specific feeding disorders, and abnormal endoscopic feeding parameters were used to predict the postoperative course of patients undergoing airway reconstruction. The relationships between diagnoses and functional feeding categories and postoperative outcomes and functional feeding categories were appraised by ,2 analysis. Results The median age of the study population was 2.5 years. Fifty-three percent of the patients were tracheotomy dependent. Only 13% of the patients had diagnoses limited to the airway, with 45% of patients having three or more diagnoses. Worse preoperative feeding abilities were associated with the presence of a tracheotomy, age 2 years or less, and multiple underlying diagnoses. Neurological diagnoses were associated with worse feeding abilities. Preoperative feeding assessments directly altered the course of management of 15% of operative patients, by recommending a delay in the surgical correction, the placement of a gastrostomy tube preoperatively, or a modification in the surgical reconstruction planned for the patient. Postoperative airway protection predictions were 80% accurate. Twelve percent of the predictions involved patients who developed unforeseen complications that required additional treatments or prolonged the hospital stay secondary to difficulties with airway protection. There was no correlation between the preoperative feeding abilities of the patients and their postoperative course after airway reconstruction. Conclusion Transient dysphagia is common after laryngotracheal reconstruction. Preoperative feeding abilities do not correlate with the postoperative airway protection abilities of a patient. Feeding assessments before pediatric airway reconstruction provide a means of identifying patients with poor airway protection mechanisms that may compromise the patient after reconstruction. Findings on swallowing evaluations that predict poor airway protective mechanisms are 1) pooling of secretions in the hypopharynx, 2) poor oral motor skills, allowing premature spillage of material into the hypopharynx where it penetrates the larynx, and 3) residue that persists in the hypopharynx after multiple swallows. The integration of information generated from the preoperative swallowing assessment promotes the selection of operative procedures that are optimal for that patient and highlights specific therapy issues that may need to be addressed in the postoperative management of the patient that may not have been obvious without the study. [source] Silencing Nogo-A promotes functional recovery in demyelinating diseaseANNALS OF NEUROLOGY, Issue 4 2010Yuhong Yang MD Objective To determine if suppressing Nogo-A, an axonal inhibitory protein, will promote functional recovery in a murine model of multiple sclerosis (MS). Methods A small interfering RNA was developed to specifically suppress Nogo-A (siRNA-NogoA). The siRNA-NogoA silencing effect was evaluated in vitro and in vivo via immunohistochemistry. The siRNA was administered intravenously in 2 models of experimental autoimmune encephalomyelitis (EAE). Axonal repair was measured by upregulation of GAP43. Enzyme-linked immunosorbent assay, flow cytometry, and 3H-thymidine incorporation were used to determine immunological changes in myelin-specific T cells in mice with EAE. Results The siRNA-NogoA suppressed Nogo-A expression in vitro and in vivo. Systemic administration of siRNA-NogoA ameliorated EAE and promoted axonal repair, as demonstrated by enhanced GAP43+ axons in the lesions. Myelin-specific T-cell proliferation and cytokine production were unchanged in the siRNA-NogoA,treated mice. Interpretation Silencing Nogo-A in EAE promotes functional recovery. The therapeutic benefit appears to be mediated by axonal growth and repair, and is not attributable to changes in the encephalitogenic capacity of the myelin-specific T cells. Silencing Nogo-A may be a therapeutic option for MS patients to prevent permanent functional deficits caused by immune-mediated axonal damage. ANN NEUROL 2010;67:498,507 [source] Dysferlin overexpression in skeletal muscle produces a progressive myopathyANNALS OF NEUROLOGY, Issue 3 2010Louise E. Glover Objective The dose,response effects of dysferlin transgenesis were analyzed to determine if the dysferlin-deficient myopathies are good candidates for gene replacement therapy. Methods We have generated 3 lines of transgenic mice, expressing low, mid, and high levels of full-length human dysferlin from a muscle-specific promoter. Transgenic skeletal muscle was analyzed and scored for morphological and functional deficits. Results Overexpression of dysferlin in mice resulted in a striking phenotype of kyphosis, irregular gait, and reduced muscle mass and strength. Moreover, protein dosage correlated with phenotype severity. In contrast to dysferlin-null skeletal muscle, no evidence of sarcolemmal impairment was revealed. Rather, increased levels of Ca2+ -regulated, dysferlin-binding proteins and endoplasmic reticulum stress chaperone proteins were observed in muscle lysates from transgenic mice as compared with controls. Interpretation Expression levels of dysferlin are important for appropriate function without deleterious or cytotoxic effects. As a corollary, we propose that future endeavors in gene replacement for correction of dysferlinopathy should be tailored to take account of this. ANN NEUROL 2010;67:384,393 [source] Protein Kinase C Activators as Synaptogenic and Memory TherapeuticsARCHIV DER PHARMAZIE, Issue 12 2009Miao-Kun Sun Abstract The last decade has witnessed a rapid progress in understanding of the molecular cascades that may underlie memory and memory disorders. Among the critical players, activity of protein kinase C (PKC) isoforms is essential for many types of learning and memory and their dysfunction, and is critical in memory disorders. PKC inhibition and functional deficits lead to an impairment of various types of learning and memory, consistent with the observations that neurotoxic amyloid inhibits PKC activity and that transgenic animal models with PKC, deficit exhibit impaired capacity in cognition. In addition, PKC isozymes play a regulatory role in amyloid production and accumulation. Restoration of the impaired PKC signal pathway pharmacologically results in an enhanced memory capacity and synaptic remodeling / repair and synaptogenesis, and, therefore, represents a potentially important strategy for the treatment of memory disorders, including Alzheimer's dementia. The PKC activators, especially those that are isozyme-specific, are a new class of drug candidates that may be developed as future memory therapeutics. [source] | ||||||||||||||||||||||||||||||||||