ABSTRACT
BACKGROUND: Cervical dystonia (CD) is a common adult-onset idiopathic form of dystonia characterized by an abnormal head posture caused by an excessive activity of the neck muscles. The position of the head is important to direct viewpoint in the rounding environment, and the body orientation, during gait, must be coherent with the subjective straight ahead (SSA). An alteration of the SSA, as in the case of CD patients, could affect gait when visual input is not available. The aim of this study was to probe the behavior of patients with CD during blindfolded walking, investigating the ability to walk straight ahead based only on somatosensory and vestibular information. METHODS: In this observational cross-sectional study, patients with CD and healthy control subjects (HC) were compared. All participants were evaluated through a gait analysis during blindfolded walking on a GAITRite carpet, relying on their own sense of straightness. RESULTS: Patients with CD showed lower values of path length (p < 0.001), a lower number of steps on the carpet (p < 0.001). A higher number of CD patients deviated during the task, walking out of the carpet, (p < 0.005) compared to HS. No relation was found between the dystonic side and the gait trajectory deviation. A significant correlation was found between pain symptom and gait performance. CONCLUSIONS: CD patients showed dysfunctions in controlling dynamic body location during walking without visual afferences, while the dystonic side does not seem to be related to the lateral deviation of the trajectory. Our results would assume that a general proprioceptive impairment could lead to an improper body position awareness in patients with CD.
Subject(s)
Torticollis , Adult , Humans , Torticollis/complications , Body Image , Gait/physiology , Neck Muscles , Walking/physiologyABSTRACT
BACKGROUND: The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. METHODS: Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. RESULTS: Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P<.005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. CONCLUSIONS: Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine.
Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/immunology , Herpes Zoster Vaccine/immunology , Herpes Zoster/prevention & control , Herpesvirus 3, Human/immunology , Aged , Case-Control Studies , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/virology , Female , Herpes Zoster/immunology , Humans , Immunity, Cellular/drug effects , Longitudinal Studies , Male , Middle Aged , VaccinationABSTRACT
Major depressive disorder has been associated with activation of inflammatory processes as well as with reductions in innate, adaptive and non-specific immune responses. The objective of this study was to evaluate the association between major depression and a disease-relevant immunologic response, namely varicella-zoster virus (VZV)-specific immunity, in elderly adults. A cross-sectional cohort study was conducted in 104 elderly community dwelling adults ≥ 60years of age who were enrolled in the depression substudy of the shingles prevention study, a double blind, placebo-controlled vaccine efficacy trial. Fifty-two subjects had a current major depressive disorder, and 52 age- and sex-matched controls had no history of depression or any mental illness. VZV-specific cell-mediated immunity (VZV-CMI) was measured by VZV responder cell frequency (VZV-RCF) and interferon-γ enzyme-linked immunospot (ELISPOT) assays, and antibody to VZV was measured by an enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). VZV-CMI, measured by VZV-RCF, was significantly lower in the depressed group than in the controls (p<0.001), and VZV-RCF was inversely correlated with the severity of depressive symptoms in the depressed patients. In addition, an age-related reduction in VZV-RCF was observed in the depressed patients, but not in the controls. Furthermore, there was a trend for depressive symptom severity to be associated with lower ELISPOT counts. Finally, VZV-RCF was higher in depressed patients treated with antidepressant medications as compared to untreated depressed patients. Since lower levels of VZV-RCF appear to explain the increased risk and severity of herpes zoster observed in older adults, these findings suggest that, in addition to increasing age, depression may increase the risk and severity of herpes zoster.
Subject(s)
Aging/immunology , Antidepressive Agents/immunology , Depressive Disorder, Major/immunology , Herpes Zoster/immunology , Herpesvirus 3, Human/immunology , Immunity, Cellular/immunology , Aged , Aged, 80 and over , Aging/blood , Analysis of Variance , Antibodies, Viral/blood , Antidepressive Agents/therapeutic use , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Depressive Disorder, Major/blood , Depressive Disorder, Major/drug therapy , Female , Herpes Zoster/psychology , Humans , Immunity, Cellular/drug effects , Male , Matched-Pair Analysis , Middle Aged , Reference Values , Risk FactorsABSTRACT
BACKGROUND: Sleep disturbances are common in patients with movement disorders. Evaluating quality of sleep is of primary importance because of the effect that nocturnal and daytime sleep abnormalities exert on general health status. However, quality of sleep has never been addressed in detail in patients with dystonia. The aim of this case-control study was to analyse quality of sleep in patients with the two most common forms of primary focal dystonia, blepharospasm (BSP) and cervical dystonia (CD). METHODS: We evaluated quality of sleep (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) in 98 patients with focal adult-onset dystonia (52 with BSP; 46 with CD) and in a group of 56 age-and gender-matched healthy subjects. The Beck Depression Inventory (BDI) was used for the evaluation of depressive symptomatology. RESULTS: Quality of sleep was impaired (significantly higher PSQI scores) in both groups of patients. However, differences in PSQI scores between patients with CD and control subjects were partly confounded by BDI scores, whereas differences in PSQI scores between patients with BSP and control subjects were not influenced by BDI. Excessive daytime sleepiness was not significantly more frequent than in control subjects in either patients with BSP or patients with CD. CONCLUSIONS: This study suggests that the assessment and treatment of insomnia-related complaints should be considered in global management plans of patients with focal dystonia, particularly in those affected by BSP.
Subject(s)
Blepharospasm/complications , Dystonic Disorders/complications , Sleep Wake Disorders/complications , Torticollis/complications , Adult , Age Factors , Aged , Aged, 80 and over , Blepharospasm/diagnosis , Case-Control Studies , Depression/complications , Depression/diagnosis , Dystonic Disorders/diagnosis , Female , Humans , Logistic Models , Male , Middle Aged , Psychiatric Status Rating Scales , Severity of Illness Index , Sex Factors , Sleep Wake Disorders/diagnosis , Sleep Wake Disorders/drug therapy , Torticollis/diagnosisABSTRACT
Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD) is an agent with adrenotoxic effect, which is able to block cortisol synthesis. This drug and radiotherapy are used also in adrenal cancer treatment even if their biological action in this neoplasia remains unknown. We investigated the effects of o,p'-DDD and ionizing radiations (IR) on cell growth inhibition and cell cycle perturbation in H295R and SW13 adrenocortical cancer cells. Both cell lines were irradiated at a 6 Gy dose and were treated with o,p'-DDD 10(-5) M separately and with IR/o,p'-DDD in combination. This combination treatment induced an irreversible inhibition of cell growth in both adrenocortical cancer cells. Cell cycle analysis showed that IR alone and IR/o,p'-DDD in combination induced the cell accumulation in the G2 phase. At 120 h after IR, the cells were able to recover the IR-induced G2 block while cells treated with IR/o,p'-DDD were still arrested in G2 phase. In order to study the molecular mechanism involved in the G2 irreversible arrest, we have considered the H295R cell line showing the highest inhibition of cell proliferation associated with a noteworthy G2 arrest. In these cells, cyclin B1 and Cdk2 proteins were examined by western blot and Cdk2 kinase activity measured by assay kit. The H295R cells treated with IR/o,p'-DDD shared an increase in cyclin B1 amount as the coimmunoprecipitation of Cdc2-cyclin B1 complex. The kinase activity also shows an increase in the treated cells with combination therapy. Moreover, in these cells, sequence analysis of p53 revealed a large deletion of exons 8 and 9. The same irreversible block on G2 phase, induced by IR/o,p'-DDD treatment, happened in H295R cells with restored wild-type p53 suggesting that this mechanism is not mediated by p53 pathway.
Subject(s)
Adrenal Cortex Neoplasms/pathology , Adrenocortical Carcinoma/pathology , Antineoplastic Agents, Hormonal/pharmacology , Mitotane/pharmacology , Radiotherapy , Adrenal Cortex Neoplasms/drug therapy , Adrenal Cortex Neoplasms/radiotherapy , Adrenocortical Carcinoma/drug therapy , Adrenocortical Carcinoma/radiotherapy , CDC2 Protein Kinase/metabolism , Cell Division/drug effects , Cell Division/radiation effects , Cell Line, Tumor , Cyclin B/metabolism , Cyclin B1 , G2 Phase/drug effects , G2 Phase/radiation effects , Humans , RNA, Messenger/metabolism , Steroids/pharmacology , Tumor Suppressor Protein p53/geneticsABSTRACT
BACKGROUND: Primary late-onset focal dystonias may spread over time to adjacent body regions, but differences in the risk of spread over time among the various focal forms and the influence of age at dystonia onset on the risk of spread are not well established. METHODS: Patients presenting with primary late-onset focal blepharospasm (BSP, n = 124), cervical dystonia (CD, n = 73) and focal hand dystonia (FHD, n = 24) with 10 years or more of disease duration (mean +/- SD, 15.3 (SD 4.9) years) were included in the study. The relationship between demographic/clinical variables and spread of dystonia was assessed by Kaplan-Meier survival curves and Cox proportional hazard regression models. RESULTS: Patients starting with BSP, CD and FHD had similar age, sex and disease duration. Age at dystonia onset, age at initial spread and the risk of initial spread were significantly higher, whereas time elapsing from onset to initial spread was significantly lower in the BSP group than in those with onset in the neck or in the upper extremities. Conversely, these parameters were similar in the CD and FHD groups. The greater risk of spread in the BSP group was mainly evident in the first 5 years of history; thereafter, it declined and became similar to that of patients with CD/FHD. The difference in the risk of initial spread by site of onset was partly confounded by age at dystonia onset. Site of and age at dystonia onset, and age at first spread, were not significant predictors of the risk of a second spread. CONCLUSION: This study adds new insights into the phenomenon of spread of primary late-onset focal dystonia and provides the framework for future studies aimed at an indepth investigation of the mechanism(s) of spread.
Subject(s)
Dystonic Disorders/diagnosis , Neurologic Examination , Age of Onset , Aged , Blepharospasm/diagnosis , Disease Progression , Female , Hand , Humans , Italy , Kaplan-Meier Estimate , Male , Middle Aged , Proportional Hazards Models , Risk Factors , Torticollis/diagnosisABSTRACT
Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have impaired postural control. Recent studies using foot sensory stimulation delivered by means of automated mechanical peripheral stimulation (AMPS) have demonstrated improvements of gait in individuals with PD. This study aimed to investigate the effects of AMPS on postural control in individuals with PD and FOG. Thirty-three subjects participated in this randomized controlled trial. Participants were allocated to two groups: AMPS and AMPS SHAM. Subjects underwent eight sessions of real (AMPS) or placebo AMPS (AMPS SHAM) once every three/four days. Postural control was assessed by means of posturography before the first and after the eighth session of treatment. We did not find positive effects of AMPS on center of pressure parameters. Thus, it seems that AMPS has no positive effect in terms of improving static postural control in individuals with PD and FOG.
Subject(s)
Gait Disorders, Neurologic/rehabilitation , Neurological Rehabilitation/methods , Outcome Assessment, Health Care , Parkinson Disease/rehabilitation , Postural Balance/physiology , Aged , Female , Gait Disorders, Neurologic/etiology , Humans , Male , Middle Aged , Parkinson Disease/complications , Physical Stimulation/methodsABSTRACT
The required coefficient of friction (RCOF) is frequently reported in the literature as an indicator of slip propensity, a consequence of the collisional aspect of legged locomotion. Little is known about the RCOF in pathological gait. Therefore, this study aimed to quantify the RCOF in subjects with Parkinson's disease (PD) and freezing of gait (FOG) during the OFF-pharma phase, and to investigate the interplay between RCOF parameters and ankle kinematic and kinetic gait variables. Fourteen subjects with PD and 14 healthy age-matched subjects were instructed to walk barefoot at self-selected speed over a force platform. The RCOF curve was obtained as the ratio between the tangential and vertical ground reaction forces. Then, the following discrete variables were identified: P1COF (the peak at the loading response phase), V1COF (the valley at midstance phase) and P2COF (the peak at push-off phase). Stepwise multiple regressions were applied to observe the influence of the gait speed and ankle kinematic and kinetic gait variables on RCOF variables. In subjects with PD and FOG the gait speed is a predictor of the RCOF in the loading response phase; plantarflexion and the plantarflexion moment are strong predictors of the RCOF in midstance; finally, push-off power is a predictor of RCOF increasing in the push-off phase. These results characterized the biomechanical strategies adopted by subjects with PD and FOG during gait in order to avoid falls.
Subject(s)
Friction , Gait , Parkinson Disease/physiopathology , Aged , Biomechanical Phenomena , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVE: To evaluate the prevalence of Chlamydia pneumoniae antibodies in an Italian population of HIV-infected and uninfected individuals in relation to the presence of HIV risk factors. DESIGN AND METHODS: A prospective evaluation of C. pneumoniae microimmunofluorescence immunoglobulin (Ig) G and IgM titres, in relation to sex, age, HIV clinical stage, and the presence of different HIV acquisition risk factors. SETTING: The Department of Infectious and Tropical Diseases, a secondary and tertiary care institution in the 'La Sapienza' University of Rome, during 1994 and 1995. PARTICIPANTS: HIV-infected and uninfected subjects (n = 322), all of them without respiratory symptoms. RESULTS: A statistically significant higher C. pneumoniae seroprevalence was found to be related, by multivariate analysis, to sex, age, and presence of HIV risk factor, but not to the presence of HIV infection itself. Among HIV-positive subjects, C. pneumoniae seroprevalence appeared to decrease with absolute CD4+ cell count and was low in Centers for Disease Control and Prevention (CDC) stage C of HIV infection. Furthermore, high C. pneumoniae IgG titres (> or = 1:512) were not found in subjects with CDC stage C disease or in those with low CD4+ cell count (< 200 x 10(6)/l). CONCLUSION: C. pneumoniae seroprevalence is higher in injecting drug users and in subjects with promiscuous heterosexual activity. A previous report of a higher C. pneumoniae seroprevalence among HIV-1-infected subjects (in relation to the normal population) was probably due to the presence of HIV risk factor and not to the HIV infection itself. HIV-infected subjects seem to have progressively lost their C. pneumoniae IgG antibodies in middle and advanced stages of HIV infection. High C. pneumoniae IgG titres are rarely found in advanced stage HIV-infected patients.
Subject(s)
AIDS-Related Opportunistic Infections/immunology , Antibodies, Bacterial/blood , Chlamydia Infections/immunology , Chlamydophila pneumoniae/immunology , HIV-1/isolation & purification , AIDS-Related Opportunistic Infections/blood , AIDS-Related Opportunistic Infections/epidemiology , Adult , Age Factors , CD4 Lymphocyte Count , Chlamydia Infections/blood , Chlamydia Infections/epidemiology , Female , Homosexuality , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Male , Multivariate Analysis , Prospective Studies , Risk Factors , Sex Factors , Substance Abuse, IntravenousABSTRACT
In a case-control study, the authors found that arterial hypertension occurred more frequently among 115 patients with primary hemifacial spasm than among 115 neurologic controls matched for age (+/-5 years), sex, and referral center. The association was not confounded by education level, smoking history, diabetes, or other diseases (adjusted OR 2.64; 95% CI 1.3 to 5.33, p = 0.007). Hypertension was significantly associated with the outcome in the left-sided group (OR 4.0; 95% CI 1.4 to 11.5), but data concerning patients with right-sided spasm were inconclusive (OR 1.05; 95% CI 0.36 to 3.1). In our sample, hypertension either preceded or followed the onset of hemifacial spasm.
Subject(s)
Hemifacial Spasm/physiopathology , Hypertension/physiopathology , Aged , Case-Control Studies , Female , Humans , Male , Middle AgedABSTRACT
OBJECTIVES: To verify the usefulness of early recording of motor evoked potentials (MEPs) in predicting motor outcome after stroke and to investigate the neural mechanisms underlying functional recovery following stroke. METHODS: We performed a comparative analysis of the behaviour of motor responses evoked by transcranial magnetic stimulation (TMS) of the ipsilateral and contralateral motor cortex in the affected and unaffected thenar muscles of 21 consecutive patients with acute stroke. RESULTS: According to the behaviour of MEPs in the affected muscles, patients could be divided into 3 groups: (a) 10 subjects with absent responses to TMS of both the damaged and undamaged hemisphere, whose motor recovery was poor and related to the size of MEPs on the normal side; (b) 5 subjects with larger MEPs upon TMS of the ipsilateral (undamaged) than of the contralateral (damaged) cortex, whose good recovery possibly resulted from the emergence of ipsilateral pathways; (c) 6 subjects with larger MEPs in the affected than in the unaffected muscles, whose good recovery was possibly subserved by alternative circuits taking over cortical deafferentation. CONCLUSIONS: Early MEP recording in acute stroke provides useful information on the clinical prognosis and the different mechanisms of motor recovery.
Subject(s)
Evoked Potentials, Motor/physiology , Stroke/physiopathology , Transcranial Magnetic Stimulation , Adult , Aged , Aged, 80 and over , Electromyography , Female , Humans , Male , Middle Aged , Muscles/physiopathologyABSTRACT
OBJECTIVES: To assess whether cortico-cortical inhibition (CCI) induced by paired-pulse transcranial magnetic stimulation (TMS) is influenced by 'preferential' or 'non-preferential' activation of the motor cortex. METHODS: Paired-pulse TMS (conditioning-test paradigm with interstimulus intervals of 2-5 ms) with a round coil centered over the vertex was performed in 10 normal subjects using opposite current flow directions. The amount of CCI in the opponens pollicis and first dorsal interosseus muscles was determined. RESULTS: When a clockwise current was induced in the brain (side A of the coil uppermost) a 'preferential' activation of the left hemisphere (right hand muscles) was observed, but the suppression of the test response by the conditioning stimulus (i.e. the CCI) was significantly greater in the left hand muscles. The situation was reversed when an anticlockwise current (side B of the coil uppermost) was induced in the brain. These effects occurred independently of the interstimulus interval, or of the absolute conditioning stimulus strength. CONCLUSIONS: CCI is more effective in the 'non-preferentially' stimulated hemisphere, and the neural elements generating the indirect I3 wave are more sensitive to intracortical inhibition than those generating the I1 wave.
Subject(s)
Motor Cortex/physiology , Transcranial Magnetic Stimulation , Adult , Analysis of Variance , Electromyography , Female , Functional Laterality/physiology , Humans , Male , Middle Aged , Reaction Time/physiologyABSTRACT
OBJECTIVE: To evaluate the motor function of the transcallosal pathways in patients with clinical diagnosis of corticobasal degeneration (CBD). METHODS: In a group of 7 patients (4 males, 3 females; mean age 70.6 years) with clinical diagnosis of probable CBD (and in 8 age-matched normal controls) we evaluated the suppression of the ongoing voluntary EMG activity in the opponens pollicis muscle induced by focal transcranial magnetic stimulation (TMS) of the ipsilateral hand motor cortex. Such ipsilateral silent period (iSP) is mediated from one motor cortex to the contralateral side via a transcallosal pathway. In addition, CBD patients were investigated with magnetic resonance imaging (MRI) and neuropsychological assessment. RESULTS: iSP was normal in 4 CBD patients, while it was bilaterally disrupted in the other 3. MRI showed an atrophy of the corpus callosum (middle-posterior part of the trunk) in the CBD patients with iSP disruption. Neuropsychological evaluation showed in patients with iSP impairment a decrease of verbal fluencies associated with an impairment of attentive function. CONCLUSIONS: A proportion of CBD patients shows physiological evidence of impaired callosal motor function and atrophy of the corpus callosum on MRI, possibly correlated to dysphasic and cognitive disorders.
Subject(s)
Corpus Callosum/physiopathology , Neural Inhibition/physiology , Neurodegenerative Diseases/physiopathology , Aged , Cognition Disorders/pathology , Cognition Disorders/physiopathology , Corpus Callosum/pathology , Electric Stimulation , Female , Humans , Magnetic Resonance Imaging , Magnetics , Male , Middle Aged , Neurodegenerative Diseases/pathology , Psychological TestsABSTRACT
Paired-pulse transcranial magnetic stimulation with a conditioning-test paradigm was used to assess changes of corticocortical inhibition and facilitation during mental simulation of sequential finger movements in normal subjects. The cortico-cortical inhibition (at interstimulus interval, ISI, of 3 ms) was significantly reduced in the relaxed opponens pollicis (OP) muscle during motor imagery, regardless of the absolute size of the test motor evoked potential. The amount of cortico-cortical inhibition was similar to that observed during a mild voluntary contraction of the OP. No change of cortico-cortical facilitation was observed at the ISI of 12 ms. The data support the hypothesis that similar neural structures, including the primary motor cortex, are activated during both mental simulation and actual execution of motor activities.
Subject(s)
Cerebral Cortex/physiology , Evoked Potentials, Motor/physiology , Magnetics , Motor Activity/physiology , Motor Cortex/physiology , Perception/physiology , Adult , Analysis of Variance , Conditioning, Psychological/physiology , Electric Stimulation , Electromyography , Humans , Movement/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Reference ValuesABSTRACT
Several clues suggest that alpha-synuclein, a presynaptic protein, plays a central role in the pathogenesis of idiopathic Parkinson's disease (PD). To search a peripheral marker of PD, we analyzed presence and amount of alpha-synuclein in CSF from 12 PD patients and 10 neurologically normal subjects. The protein was extracted from CSF samples through immunoprecipitation and immunoblotting with different specific anti-alpha-synuclein antibodies. We identified a 19 kDa band that corresponds to monomeric alpha-synuclein, given its comigration with homologue human recombinant peptide as well as with the protein extracted from cerebral cortex of normal subjects. The amount of CSF 19 kDa alpha-synuclein did not significantly vary in PD and normal cases. These findings have two implications: (a) full length alpha-synuclein is released by neurons in the extracellular space; (b) alpha-synuclein does not appear a peripheral marker of PD pathology.
Subject(s)
Nerve Tissue Proteins/cerebrospinal fluid , Parkinson Disease/cerebrospinal fluid , Biomarkers/cerebrospinal fluid , Humans , Immunoblotting , Synucleins , alpha-SynucleinABSTRACT
Transcranial magnetic stimulation with a conditioning-test paradigm was used to assess cortico-cortical interactions in the motor cortex of 11 patients with Huntington's disease (HD) as compared to normal controls (NC). In the HD patients, threshold and amplitude of motor potentials evoked in the opponens pollicis muscle at rest were not significantly different from NC. The cortico-cortical inhibition at interstimulus intervals of 2-5 ms was significantly reduced and the cortico-cortical facilitation at longer intervals (10-25 ms) was significantly enhanced. Changes of intracortical inhibition and facilitation were related to clinical rating of choreic dyskinesias. The data support the hypothesis of a functional impairment of the motor cortex-basal ganglia loop in HD patients.
Subject(s)
Huntington Disease/physiopathology , Magnetics , Motor Cortex/physiopathology , Neural Inhibition/physiology , Adult , Conditioning, Psychological/physiology , Electric Stimulation , Electromyography , Evoked Potentials, Motor/physiology , Female , Humans , Male , Middle AgedABSTRACT
Patients that are followed by nephrologists from the beginning of the illness, they show a deceleration in the progression of the Chronic Kidney Disease towards dialysis and a better quality of life (less osteodystrophy, anaemia and fluids overload, better pressure management). However, in 2013 it still exists a great lack of knowledge about the professional figure of nephrologist. Residents of Nephrological School of Catania decided to conduct a survey to evaluate common knowledge of renal diseases and their treatments. The survey was conducted in two cities of Sicily. The results show that people are generally uninformed and disoriented about renal illness and their risks.
Subject(s)
Health Knowledge, Attitudes, Practice , Kidney Diseases , Nephrology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Italy , Male , Middle Aged , Young AdultABSTRACT
OBJECTIVES: We investigated the antiproliferative effect of Myc down-regulation via cell proliferation inhibition, cell cycle perturbation and apoptosis in two human astrocytoma models (T98G and ADF) steadily expressing an inducible c-myc Anti-sense RNA. MATERIALS AND METHODS: Cell growth experiments were performed using the trypan blue dye exclusion test and cell cycle analysis was evaluated by flow cytometry. Cell cycle molecules were detected by Western blot analysis, co-immunoprecipitation and reverse transcription-polymerase chain reaction assays. RESULTS: We showed that Myc down-regulation in astrocytoma cells led to G1 accumulation and an inhibition of cell proliferation characterized by S phase delay. Co-immunoprecipitation experiments detected formation of inactive cyclin D1/cdk4 complexes as evaluated by presence of an active unphosphorylated form of retinoblastoma protein, the best characterized target substrate for cyclin D1/cdk4 complex, in ADF pINDc-myc anti-sense 7 cells. We also found that either p57Kip2 "apice" or p27Kip1 "apice" inhibitors bound to cyclin D1/cdk4 complex, thus, suggesting that they cooperated to inhibit the activity of cyclin D1/cdk4. Moreover, c-Myc down-regulation led to activation of the apoptotic mitochondrial pathway, characterized by release of cytochrome c and Smac/Diablo proteins and by reduction of c-IAP levels through activation of proteasome-mediated protein degradation system. CONCLUSIONS: Our results suggest that c-Myc could be considered as a good target for the study of new approaches in anticancer astrocytoma treatment.
Subject(s)
Apoptosis/genetics , Astrocytoma/metabolism , Cyclin D1/metabolism , Cyclin-Dependent Kinase 4/metabolism , Down-Regulation , Genes, myc , Intracellular Signaling Peptides and Proteins/physiology , Mitochondrial Proteins/physiology , Apoptosis Regulatory Proteins , Astrocytoma/enzymology , Astrocytoma/pathology , Base Sequence , Blotting, Western , Cell Cycle , Cell Line, Tumor , DNA Primers , Gene Silencing , Humans , RNA, Small Interfering/genetics , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND: A double-blind, placebo-controlled trial that involved 38,546 subjects > or =60 years old demonstrated efficacy of a high-potency live-attenuated Oka/Merck varicella-zoster virus (VZV) vaccine. The trial included an immunology substudy to determine the relationship of VZV-specific immune responses to vaccination and clinical outcome. METHODS: The immunology substudy enrolled 1395 subjects at 2 sites where blood samples obtained prior to vaccination, at 6 weeks after vaccination, and at 1, 2, and 3 years thereafter were tested for VZV-specific cell-mediated immunity (VZV-CMI) by gamma-interferon ELISPOT and responder cell frequency assays and for VZV antibody by glycoprotein ELISA. RESULTS: VZV-CMI and VZV antibodies were significantly increased in vaccine recipients at 6 weeks after vaccination. The vaccine-induced increases in VZV-CMI persisted during the 3 years of follow-up, although their magnitude decreased over time. The magnitude of these VZV-specific immune responses was greater in subjects 60-69 years old than in subjects > or =70 years old. CONCLUSIONS: The zoster vaccine induced a significant increase in VZV-CMI and VZV antibody. The magnitude and duration of the boost in VZV-CMI in vaccine recipients and the relationship of this boost to age paralleled the clinical effects of the vaccine observed during the efficacy trial. These findings support the hypothesis that boosting VZV-CMI protects older adults against herpes zoster and postherpetic neuralgia.
Subject(s)
Herpes Zoster Vaccine/immunology , Herpes Zoster/prevention & control , Herpesvirus 3, Human/immunology , Age Factors , Aged , Antibodies, Viral/blood , Double-Blind Method , Female , Herpes Zoster/immunology , Herpes Zoster/virology , Herpes Zoster Vaccine/blood , Herpes Zoster Vaccine/pharmacokinetics , Herpes Zoster Vaccine/therapeutic use , Humans , Immunity, Cellular , Male , Vaccines, Attenuated/immunology , Vaccines, Attenuated/pharmacokinetics , Vaccines, Attenuated/therapeutic useABSTRACT
OBJECTIVE: Freezing of gait is a frequently disabling symptom in Parkinson's disease, poorly responding to dopaminergic treatment. We investigated the short-term effectiveness of a rehabilitation protocol in parkinsonian patients with freezing of gait. DESIGN: Prospective, uncontrolled pilot study with open label design. SETTING: Outpatient service for rehabilitation of neurological disorders. SUBJECTS: Twelve patients (8 male, 4 female; aged 59-78 years; Hoehn-Yahr stage: 2-3; mean disease duration: 14.2 +/- SD 4.1 years). INTERVENTIONS: Patients attended three (45 min) sessions every week, over a six-week period, of physical therapy focused to improve balance, postural control and walking, and to learn new strategies for overcoming freezing of gait. MAIN OUTCOME MEASURES: Patients were evaluated before (T0), at the end (T1), and one month after (T2) rehabilitation by means of clinical rating scales (Unified Parkinson Disease Rating Scale--Motor Section; Freezing of Gait Questionnaire; Parkinson Disease Quality of Life Score) and gait parameters (number of strides, stride length and velocity) during a standardized walking test. RESULTS: The scores of Freezing of Gait Questionnaire and of Parkinson Disease Quality of Life Questionnaire (but not of the Unified Parkinson Disease Rating Scale--Motor Section) were significantly improved after treatment (T1). Gait parameters were significantly improved at T1 and T2. CONCLUSIONS: We showed the potential short-term efficacy of a rehabilitative approach to freezing of gait in Parkinson's disease. The positive outcome was documented by clinical rating scales and objective gait evaluation. The rapid reversibility of the clinical benefit suggests that further studies are needed to better define the optimal frequency and duration of treatment.