An intensive task-oriented circuit training positively impacts gait biomechanics in MS patients.

BACKGROUND: An intensive task-oriented circuit training (TOCT) provides a valid approach in improving motor function in Multiple Sclerosis (MS). OBJECTIVE: We aimed at testing the efficacy of TOCT on gait kinematics in MS patients with mild-moderate disability. METHODS: Nineteen MS patients able of independent walking performed 3-D Gait Analysis before (T0) and after (T1) a two-week TOCT program. Patients were clustered in two different subgroups, according to clinical neurological impairments assessed with specific functional system of Expanded Disability Status Scale (EDSS): pyramidal (Group 1) and cerebellar (Group 2) subjects. Spatio-temporal and kinematic data were compared before and after the TOCT intervention in the total sample of patients and in the two selected subgroups at two time intervals. RESULTS: Data obtained revealed increased dynamic ROM at knee joint after training in the whole study sample. Of note, knee dynamic excursion improved significantly in Group 1 but not in Group 2 patients after TOCT. Moreover, sagittal plane kinematics revealed significant modifications on knee and ankle biomechanics in Group 1 after rehabilitation. CONCLUSIONS: These data point out the benefits of the task specific training on gait dynamics in mild impaired MS subjects, linking to treatment opportunity in patients with a prevalent pyramidal impairment.

Cilostazol reduces dry eye symptoms and improve walking distance in patients with peripheral artery disease.

AIM OF THE STUDY: Cilostazol is a phosphodiesterase III inhibitor that has anti-inflammatory and immunomodulatory effects and can act with beneficial effect in Dry Eye Syndrome (DES). This clinical trial evaluates the effects of cilostazol on the tear film. MATERIALS AND METHODS: Following the run-in period, subjects were randomly into two groups: 40 subjects treated with cilostazol and 40 no-treated subjects. The Walking Impairment Questionnaire (WIQ) has been administered to all patients. RESULT: The data obtained from comparison of the two study groups A and B were, respectively, the following: Schirmer I: 10.2±0.2 Vs 13.8±0.4 (p< 0.001); Schirmer II: 3.8±0.1 Vs 4.6±0.2 (p<0.001); Break-up time (BUT) 4.2±0.3 Vs 6.5±0.2 (p<0.001) with disappearing of symptoms. The WIQ showed a significant difference in the walking distance (p<0.05) and calf pain severity (p<0.005) of treated patients. In comparison with the placebo group, treated patients showed an improvement (p<0.03) in calf pain severity. CONCLUSION: The administration of cilostazol was effective, in reducing DES and improve walking distance questionnaire.

Static postural control disturbances among the different multiple sclerosis phenotypes: A Neurocom Balance Manager® evaluation study.

BACKGROUND: The computerized stabilometric platform can be used and privileged over clinical scales, as self-administered questionnaires to asses postural control and balance evaluation in Multiple sclerosis (MS). Aim of our study was to evaluate static postural control assessed by Neurocom Balance Manager® through the modified Clinical Test of Sensory Interaction on Balance (mCTSIB) in relapsing-remitting MS (RRMS), progressive MS (PMS) and CIS, compared to healthy controls (HC). METHODS: We screened MS patients consecutively referring to our MS Center at University of Catania, during July 2013-June 2014 diagnosed as CIS, RRMS and PMS. All MS patients underwent clinical and neurological evaluations and a complete postural exam by Neurocom Balance Manager® in order to evaluate Center of Pressure (COP), through mCTSIB. We evaluated the following parameters: Total Path Length-open eyes (TPL-OE), Total Path Length-closed eyes (TPL-CE), Sway Area-open eyes (SA-OE), Sway Area-closed eyes (SA-CE), Mean sway velocity-open eyes (MSV-OE), Mean sway velocity-closed eyes (MSV-CE). Additionally, patients were tested by Berg balance scale (BBS) for balance and Barthel Index (BI) for disability outcomes. RESULTS: Out of 170 MS patients assessed for eligibility, 163 met the inclusion/exclusion criteria and were finally enrolled. All balance parameters were found more impaired in MS group compared to controls and CIS. Moreover, no differences in terms of balance assessment were found between HC and CIS. The correlation analysis showed that BBS was strongly associated to SA-OE, SA-CE, TPL-OE and MSV-OE. We also found a correlation between BI and SA-CE. CONCLUSION: Our study revealed significant differences among HCs, CIS and MS. MS, especially PMS, exhibit the worst balance performances especially in EC trials. The higher correlation between balance parameters, especially sway area, and BBS score confirmed the reliability and sensibility of mCTSIB assessment in evaluating static postural control in MS patients.

Late-onset and young-onset relapsing-remitting multiple sclerosis: evidence from a retrospective long-term follow-up study.

BACKGROUND AND PURPOSE: Late-onset multiple sclerosis (MS) has a prevalence of about 10-20% in natural history MS studies. Few data have been published about the long-term disease trajectory in the cohort of late-onset relapsing-remitting MS (LORRMS). The aim of this study was to identify the risk factors for reaching an Expanded Disability Status Scale (EDSS) score of 6.0 in LORRMS (onset at >40 years of age) and young-onset relapsing-remitting MS (YORRMS) (onset between 18 and 40 years of age). METHODS: Clinical and radiological [magnetic resonance imaging (MRI) of the brain] follow-up data were collected. Disability was assessed by EDSS score. A Cox proportional hazards model was used to evaluate the demographic and clinical predictors of reaching an EDSS score of 6.0 in the two cohorts. RESULTS: A total of 671 patients with relapsing-remitting MS were enrolled, 143 (21.3%) with LORRMS and 528 (78.7%) with YORRMS. In LORRMS, age at onset was 47.8 ± 5.3 (mean ± SD) years and duration of follow-up was 120.7 ± 52.7 months. In YORRMS, age at onset was 27 ± 2.7 years and duration of follow-up was 149.9 ± 92.7 months. The survival curve analyses showed a higher probability of reaching an EDSS score of 6.0 for LORRMS in a shorter time (months) than for YORRMS (94.2 vs. 103.2 months; log-rank 8.8; P < 0.05). On MRI, YORRMS showed more brain inflammatory features than LORRMS. In the multivariate Cox model, age at onset [Exp(B) value, 6.5; 95% confidence interval, 1.9-22.6; P < 0.001] and male gender [Exp(B) value, 1.7; 95% confidence interval, 1.0-2.8; P < 0.05] were the strongest predictors of reaching an EDSS score of 6.0. CONCLUSIONS: The male population with LORRMS reached severe disability faster than those with YORRMS, even when YORRMS showed more brain inflammatory features on MRI.

Bilateral cortical representation of tactile roughness.

Roughness is the most important feature for texture discrimination. Here we investigate how the bilateral cortical representation of touch is modulated by tactile roughness by analyzing the neural responses elicited by stimuli with various coarseness levels ranging from fine to medium. A prolonged stimulation was delivered to 10 healthy subjects by passively sliding tactile stimuli under the fingertip while recording the EEG to study the modulation of Somatosensory Evoked Potentials (SEPs) as well as activity in the theta and alpha bands. Elicited long-latency SEPs, namely bilateral P100-N140 and frontal P240 were consistent across stimuli. On the contrary, the temporal lag N140 - P240 was nonlinearly modulated both in contralateral and ipsilateral sides, in agreement with literature. Using a time-frequency analysis approach, we identified a theta band power increase in the [0 0.5]s interval and a partially overlapped power decrease in the alpha band which lasted throughout the stimulation. The estimated time these two phenomena were overlapped was comparable across stimuli, whereas a linear decrease in alpha band amplitude was reported when increasing the stimulus roughness in both contralateral and ipsilateral sides. This study showed that the selected tactile stimuli generated physiological bilateral responses that were modulated in a diversified way according to the stimulus roughness and side. Specifically, we identified sensory processing features (i.e., theta and alpha time overlap) invariant to the stimulus roughness (i.e., associated to a basic cortical mechanism of touch) and roughness-dependent cortical outputs comparable in the contralateral and ipsilateral sides that confirm a bilateral processing of tactile information.

Lateral switch to IFN beta-1a 44 mcg may be effective as escalation switch to fingolimod in selected persons with relapsing remitting multiple sclerosis: a real-world setting experience.

BACKGROUND: The efficacy of lateral and escalation switch is a challenge in MS. We compared in a real-world setting the efficacy of switching to IFN beta-1a 44 mcg or to fingolimod in persons with relapsing remitting MS (pwRRMS) who failed with others injectable IFNs or glatiramer acetate. RESEARCH DESIGN AND METHODS: retrospective analysis of 24 months prospectively-collected data at the MS center of the University of Catania, Italy was performed. Patients who were switched to IFN-beta 1a 44 mcg or fingolimod were analyzed using propensity-score covariate adjustment model within demographic (e.g. age and gender) and disease (e.g. timing of pre-switch relapse) characteristics. Switching-time was considered the starting-time of the observation. RESULTS: 43 pwRRMS on IFN beta-1a 44 mcg and 49 pwRRMS on fingolimod were included. Baseline characteristics differed for EDSS score and number of T2 lesions (higher in group on fingolimod). At 24 months of follow up, both groups showed no differences in the survival curves of reaching a first new relapse, new T2 and Gd+ MRI brain lesions, even corrected for the propensity score covariate adjustment. CONCLUSIONS: lateral switch to IFN beta-1a 44 mcg and escalation switch to fingolimod showed same ability in influencing RRMS disease activity at 24 months.

Etiology of chronic skin lesions in subjects with peripheral arterial disease.

INTRODUCTION: Skin lesions can be defined as lesions that result in loss of tissues and their joints, and often this cutaneous skin process is a primary or secondary consequence of the structural changes in the skin itself. Subjects with peripheral arteripathies that develop chronic skin lesions in the lower extremities of the Western world are constantly increasing. We conducted a study on the etiologic incidence of chronic skin lesions in peripheral arterial disease CSLpa subjects in the lower limbs compared to subjects with chronic skin lesions CSL (controls). MATERIALS AND METHODS: 30 subjects with peripheral atheropathies PA (22 F - 8 M mean age 74,5 ± 4,9) and with chronic skin lesions (CSLpa) in the lower limbs "A" group were admitted to our study according to a randomized and compared to 30 no peripheral atheropathies subjects (19 F-11 M, mean age 81,5 ± 7,3 - controls) group B with chronic skin lesions (CSL). These two groups "A" and "B" have been studied and compared on the basis of infectious etiology responsible for the infectious skin process. RESULTS: In the subjects of the "A" group we found a 12 positive assay of 40.0% of the examinations, while in the group "B" we achieved a total cultured positivity of 9 cases corresponding to 30.0% of the examinations . For the number of bacterial species identified for "A" group we obtained 3 mono microbial and 6 poly microbial bacteriological tests and for group "B" we observed 7 mono microbial and 2 poly microbial tests. All bacteriological isolates showed "in vitro" sensitivity to satisfactory ciprofloxacin with MICs range of 0.78-1.56mg/L. The data observed after 4 weeks after the amniotic membrane (MA) in the two study groups A and B were respectively the following: and for group A 50% scarring, 46.6% partial resolution and in one case worsening for the B-healing group in 63.3%, the partial resolution in the remaining 36.6. CONCLUSIONS: The data from this study show a different etiology between subjects with CSLpa than subjects with CSL. This phenomenon confirms an alteration of the skin microbioma of subjects with peripheral arteriopathy and chronic skin lesions with modification of the opportunistic role of some species of cutaneous bacterial flora.

A multicenter, observational, prospective study of self- and parent-reported quality of life in adolescent multiple sclerosis patients self-administering interferon-ß1a using RebiSmart™-the FUTURE study.

Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-ß1a (Rebif; 22 µg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being "Emotional functioning." In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points, p = 0.041). Significant increases were also evident for parent-reported "Psychosocial health summary score" (+ 5.90 points; p = 0.015) and "School functioning" (+ 7.84 points; p = 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart™ for self-administration of Rebif® can experience long-term improvements in QL.

The mixture of bifidobacterium associated with fructo-oligosaccharides reduces the damage of the ocular surface.

BACKGROUND: Despite its high prevalence Dry Eye Syndrome (DES) in frequently under-recognized owing to its negative influence on patients visual function. METHODS: This clinical trial was a pilot study to evaluate the effects of supplementation with mixture (Bifidobacterium lactis and Bifidobacterium bifido) on the tear film. Following the run-in period subjects were randomized in two groups: group A (N°20 subjects) and group B (N°20 subjects). Group A (control) treated only with substitute tear and group B treated with substitute tear + mixture (symbiotic). RESULTS: The data obtained in the two study groups A and B were, respectively the following: Schirmer 9.1±0.2 vs 12.7±0.4 (p< 0.001); Schirmer II 3.5±0.1 VS 4.7±0.2 (p<0.001); BUT 3.9±0.3 vs 6.3±0.2 (p<0.001). Culture test showed initial bacterial growth in group "A" (placebo) 18 out of 40 samples tested, corresponding to 45.0% and "B" after treatment ((symbiotic) was found positive culture whit growth of bacteria in 12 tests equal to 30.0%. The total numbers of isolations of aerobic and anaerobic bacteria found group A and B after treatment. A reduction of 15 to 11 strains of aerobic and anaerobic isolates from 9 to 5 has been found. CONCLUSIONS: The present study shows that the administration of bifidobacterium may represent a success full treatment in ameliorating dry eye syndrome (DES). The effect of imbalanced microbiota are not restricted by gastrointestinal abnormalities but could have systemic impact on immunity. Commensal bacteria or probiotics interact with the endogenous enteric microbiota and gut cells therein confereing health benefit to the host.

Gait dynamics in Pisa syndrome and Camptocormia: The role of stride length and hip kinematics.

This is an observational cross-sectional study evaluating gait dynamics in patients with Parkinson's Disease (PD) and severe postural deformities, PD without axial deviations and healthy subjects. Ten PS individuals with Pisa syndrome (PS) and nine subjects with Camptocormia (CC) performed 3-D Gait Analysis and were evaluated with walking and balance scales. Correlations with clinical and functional scales were investigated. Spatio-temporal and kinematic data were compared to ten PD subjects without postural deformities (PP) and ten healthy matched individuals (CG). Data obtained showed decreased walking velocity, stride and step length in PP, PS and CC groups compared to controls. The correlation analysis showed that stride and step length were associated with reduced functional abilities and disease severity in PS and CC groups. Kinematic data revealed marked reduction in range of movements (ROMs) at all lower-extremity joints in PS group. While, in CC group the main differences were pronounced in hip and knee joints. PS and CC groups presented a more pronounced reduction in hip articular excursion compared to PP subjects, revealing an increased hip flexion pattern during gait cycle. Moreover, the increased hip and knee flexion pattern adversely affected functional performance during walking tests. Results obtained provide evidence that step length, along with stride length, can be proposed as simple and clear indicators of disease severity and reduced functional abilities. The reduction of ROMs at hip joint represented an important mechanism contributing to decreased walking velocity, balance impairment and reduced gait performance in PD patients with postural deformities.

Long-latency components of somatosensory evoked potentials during passive tactile perception of gratings.

Perception of tactile stimuli elicits Somatosensory Evoked Potentials (SEPs) that can be recorded via non-invasive electroencephalography (EEG). However, it is not yet clear how SEPs localization, shape and latency are modulated by different stimuli during mechanical tactile stimulation of fingertips. The aim of this work is thus to characterize SEPs generated by the tactile perception of gratings during dynamic passive stimulation of the dominant fingertip by means of a mechatronic platform. Results show that a random sequence of stimuli elicited SEPs with two long-latency components: (i) a negative deflection around 140 ms located in the frontal-central-parietal side in the contralateral hemisphere; (ii) a positive deflection around 250 ms located in the frontal-central midline. Time-frequency analysis revealed significant continuous bilateral desynchronization in the alpha band throughout the passive stimulation. These results are a fundamental step towards building a model of brain responses during perception of tactile stimuli for future benchmarking studies.

Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia.

BACKGROUND: Gait impairment, balance problems and falls have a negative impact on independence in ADL and quality of life of patients affected by Hereditary Spastic Paraplegia (HSP). Since no pharmacological options are available, treatments rely mostly on rehabilitation therapy, although almost no data on this topic exist. Given the demonstrated effectiveness of robotics in improving gait and balance in various neurological diseases, aim of this study is to test the effectiveness of a robotic-aided program of gait training on balance, walking ability and quality of life in adult subjects affected by uncomplicated HSP. METHODS: Thirteen patients affected by uncomplicated HSP were subjected to a six-week robotic-aided gait training protocol. Participants underwent a battery of 3 walking test, 1 balance test and 2 quality of life questionnaires. RESULTS: At the end of the treatment a significant improvement of balance, walking ability and quality of life was observed in almost all the tests. The improvements were maintained over a two-month follow-up period. CONCLUSIONS: Our study indicates that a robotic gait training is long term effective in improving balance and walking ability with a positive impact on quality of life in patients affected by uncomplicated form of HSP. As currently there is no specific treatment to prevent or reverse HSP progression, our contribution would be significant for the development of exercise recommendations in this rare disease.

Robot-assisted gait training improves motor performances and modifies Motor Unit firing in poststroke patients.

BACKGROUND: Robotics and related technologies are realizing their promise to improve the delivery of rehabilitation therapy but the mechanism by which they enhance recovery is still unknown. The electromechanical-driven gait orthosis Lokomat has demonstrated its utility for gait rehabilitation after stroke. AIM: To test the efficacy of Lokomat in gait retraining and to investigate the neurophysiological mechanisms underlying the recovery process. DESIGN: Case series study. SETTING: Unit of Neurorehabilitation of a University Hospital. POPULATION: Fifteen patients with post-stroke hemiparesis. METHODS: Patients underwent a six weeks rehabilitative treatment provided by Lokomat. The outcome measures were: Fugl-Meyer Motor Scale (FMMS), Berg Balance Scale (BBS), 10 metres Walking Test (10mWT), Timed Up and Go test (TUG), 6 Minute Walking Test (6MWT). Strength and Motor Unit firing rate of vastus medialis (VM) were analyzed during isometric knee extension through an isokinetic dynamometer and surface EMG recording. RESULTS: An increase of duration and covered distance, a decrease of body weight support and guidance force on the paretic side along the sessions were observed. The FMMS, the BBS, the TUG and the 6MWT demonstrated a significant improvement after the training. No increase of force was observed whereas a significant increase of firing rate of VM was recorded. CONCLUSION: The evidence that the improvement of walking ability observed in our study determines a significant increase of firing rate of VM not accompanied by an increase of force could suggest an effect of training on motorneuronal firing rate that thus contributes to improve motor control. CLINICAL REHABILITATION IMPACT: Given the current wide use of robotics in gait retraining after stroke, our approach can contribute to clarify the mechanisms underlying its rehabilitative impact so as to incorporate the findings of evidence-based practice into appropriate treatment plans for persons poststroke.

Benefits of an intensive task-oriented circuit training in Multiple Sclerosis patients with mild disability.

BACKGROUND: Exercise is well tolerated and induces relevant improvements in physical and mental functioning of persons with Multiple Sclerosis (MS). Unfortunately, due to the wide variety of symptoms and the broad range of exercise interventions, it is not possible to make unified exercise recommendation as to what type of exercise is safe and effective for persons with MS. OBJECTIVE: The aim was to test the impact of an intensive task-oriented training on motor function and quality of life in 17 MS patients with an Expanded Disability Status Scale (EDSS) between 4 and 5.5. METHODS: Patients underwent a two-week intensive, task-oriented rehabilitation program. Outcome measures were: Berg Balance Scale, Gait Dynamic Index, 6 Minute Walking Test, Physiological Cost Index, Fatigue Severity Scale, 10 metres Walking Test, Timed Up and Go test, Short form 36, Multiple Sclerosis Impact Scale, Patient Health Questionnaire. RESULTS: All outcome measures showed a significant improvement after the treatment except for the 6 Minute Walking test and the Short form 36 that showed a trend of improvement although not statistically significant. CONCLUSIONS: An intensive task-oriented rehabilitation protocol is effective in improving motor function and has a positive impact on quality of life in MS patients with moderate disability.

Abnormal lactate levels in patients with polymyositis and dermatomyositis: the benefits of a specific rehabilitative program.

BACKGROUND: Polymyositis (PM) and Dermatomyositis (DM) are chronic, inflammatory and autoimmune skeletal muscle disorders characterized by reduced muscle strength, fatigue and myalgia. While inflammation causes muscle damage in the early phase, metabolic alterations such as an impairment of oxidative metabolism seem to be responsible for the disability in the chronic phase of the disease. AIM: To assess muscle oxidative efficiency and to test the effect of aerobic training in a group of PM/DM patients. DESIGN: A case-control study and a within-group comparison. SETTING. Outpatients of the Unit of Neurorehabilitation of the University Hospital of Pisa. POPULATION: 20 patients with myositis (15 PM and 5 DM) and 15 healthy subjects as a control group. METHODS: The test consisted of an incremental, sub-maximal aerobic exercise on a treadmill; haematic lactate was assessed at rest and after 1', 5', 10' and 30' minutes from the end of the exercise. A within-group comparison was conducted on four of the PM patients (P group). They were subjected to six weeks aerobic training. Lactate curve and functional tests were assessed before and after the treatment. RESULTS: A precocious fatigability and significantly higher values of lactate at rest and after the exercise were observed in patients. In the P group mean lactate levels were significantly decreased after the treatment and an improvement of muscle performance was observed. CONCLUSION: Abnormal blood lactate levels suggested an impaired muscle oxidative efficiency in PM/DM patients. A specific aerobic training program reduced lactate levels and relieved fatigue symptoms in a within-group of four of the PM patients. CLINICAL REHABILITATION IMPACT: Such a specific aerobic training program could be introduced in everyday practice for the rehabilitative treatment of PM/DM patients.

Intensive aerobic training improves motor performances and oxidative metabolism efficiency in chronic polymyositis: a case report.

We describe the case of a 64-year-old woman affected by chronic polymyositis with gait disturbance, fatty replacement and swelling of thigh muscles. She achieved significant clinical improvement after 5 weeks intensive aerobic training. In particular the patient improved in motor performance tests, showed an improvement in the efficiency of oxidative metabolism and quality of life. Furthermore, analysis of creatinephosphokinase levels showed a reduction of muscle damage susceptibility. In conclusion, a specific intensive exercise program can be safely used with beneficial effects on muscle function in patients with chronic polymyositis.

Skeletal muscle and nutritional assessment in chronic renal failure patients on a protein-restricted diet.

BACKGROUND: The close relationship between protein-energy malnutrition and quality of life, morbidity and mortality, makes mandatory a careful evaluation of the nutritional status and muscle mass in chronic renal failure (CRF) patients. METHODS: Nutritional and skeletal muscle data were obtained from 28 nondiabetic patients with severe CRF (glomerular filtration rate, GFR < 15 mL min-1) on conservative treatment. Of them, 14 (8 males, 4 females) were on a conventional low-protein (0.6 g kg-1 body weight) diet (LPD) and 14 (8 males, 4 females) were on a very low-protein (0.3 g kg-1 body weight) diet supplemented with essential amino acids and ketoacids (Ketodiet); 28 healthy sex- and age-matched subjects served as controls. We evaluated biochemistry, anthropometry, bioelectrical impedance vector analysis, and three noninvasive tests investigating some skeletal muscle features: (a) myoelectrical fatigue phenomenon was studied using a surface electromyography technique that provides data on conduction velocity (CV), median frequency of power spectrum (MDF) and average rectified value (ARV) of myofibre action potential, at 15 and 35 Hz stimulation frequency; (b) muscle oxidative metabolism was studied by serum lactate following aerobic exercise; and (c) muscle strength of the legs was studied using an isokinetic exercise test at two different angular velocities (60 degrees and 180 degrees s-1). RESULTS: No difference between patients and controls was detected regarding CV, MDF and ARV, at 35 and 15 Hz testing. Serum lactate was higher in patients than in controls at 1, 5, 10 and 30 min recovery. A decreased knee extension and flexion strength was detected in CRF patients both at low (60 degrees s-1) and at high (180 degrees s-1) angular velocity; muscle strength deficit negatively correlated to serum albumin (r = -0.52, P < 0.01), but no relationship was found with protein intake or residual renal function. No difference was found between LPD and Ketodiet patients regarding the studied muscular tests as well as the anthropometry and bio-impedance data. CONCLUSIONS: Implementation of a proper dietary regimen, including severe restriction of protein intake can preserve lean body mass and nutritional status of advanced CRF patients. Skeletal muscle shows unchanged sarcolemma excitability but abnormal oxidative metabolism and reduced segmental strength. Regular physical activity and a close clinical and dietary monitoring should be recommended for the predialysis patient care.

Spontaneous chromosome loss and colcemid resistance in lymphocytes from patients with myotonic dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is one of the many inherited human diseases whose molecular defect is the expansion of a trinucleotide DNA sequence. DM1 shares with fragile X syndrome (FMR1), another "unstable triplet syndrome", several molecular features not present in the remaining triplet diseases. As FMR1 is also characterised by chromosome instability at the site of the expanded triplet, lymphocytes from DM1 patients and healthy donors were cultured for micronucleus (MN) analysis, in order to verify if DM1 is also prone to chromosome instability. A FISH analysis was also carried out to detect the presence of centromeric sequences in the observed MN. The data indicate that DM1 patients present a percentage of centromere-positive MN significantly higher than controls, suggesting that chromosome loss is the main mechanism underlying the origin of the increased spontaneous instability. To further assess the proneness to instability of cells of DM1 patients, cultures from patients and controls were treated in vitro with growing concentrations of two different mutagens: colcemid, a "pure" aneugen compound whose target is tubulin, and mytomicin C, a strong clastogen. The results show that the patient group is significantly less sensitive to colcemid. These data, together with FISH analysis, suggest the presence, in DM1 patients, of an already damaged tubulin, which becomes no more sensitive to the effect of colcemid and which could be the main defect underlying the aneugenic effects in DM1.

A surface EMG analysis of sarcolemma excitability alteration and myofibre degeneration in Steinert disease.

OBJECTIVES: To apply surface electromyography (EMG) using low and high stimulation frequencies, to establish the contribution of myotonia and/or dystrophy to muscle impairment in subjects affected by myotonic dystrophy (MyD). METHODS: A motor point stimulation protocol, at 15 and 35 Hz, was carried out on the tibialis anterior (TA) of 25 MyD patients. These were subdivided into 3 subgroups, MyD3 (9), MyD4 (10) and MyD5 (6), on the basis of their TA MRC score. The surface myoelectric signal was recorded and the average rectified value of amplitude (ARV) was evaluated. In 4 MyD5 patients we simultaneously recorded EMG and force. RESULTS: Each subgroup presented a characteristic ARV trend both at 15 and 35 Hz - increasing in MyD3 (like the controls), slightly decreasing in MyD4 and clearly decreasing in MyD5. The low frequency permitted a greater resolution of the statistical analysis. Two out of 4 patients showed an opposite trend of ARV with respect to the force, whereas the others presented a parallel decreasing trend. CONCLUSIONS: The analysis of the ARV during a stimulated contraction permits the identification and quantification of the sarcolemma excitability alteration and/or the myofibre degeneration contributing to muscle impairment in MyD. The lower frequency is more sensitive and offers better inter-experiment repeatability.

Abnormal increase of creatine kinase plasma levels following muscle exercise in nephrotic patients.

Nephrotic syndrome is a protein-wasting disorder affecting total body protein metabolism, often leading to reduction of lean body mass and changes of muscle cell composition. The aim of this study was to investigate the susceptibility to muscle cell damage in nephrotic patients following submaximal physical exercise, by detection of the creatine kinase (CK) plasma level changes. Fourteen patients affected by primary nephrotic syndrome, without chronic renal failure, underwent an exercise test on a cycle ergometer for 20 min at a constant speed (60 rpm). In each subject, the work rate (expressed as watts) was established as 70% of the maximum power theoretically calculated on a sex, age, weight and height basis. CK plasma levels (U/l) were determined before and 1, 3, 6 and 24 h after the exercise. Following exercise, CK plasma levels became higher in nephrotics than in normal controls. That is, the amount of CK increments was greater in nephrotics than in controls from the first hour after the end of exertion. These changes, both as absolute values and as percentage of the basal values, correlate positively to daily urinary protein losses; moreover, an inverse relationship was detected with albumin serum levels. However, no correlation was observed between the amount of plasma CK increases and age, body weight, plasma creatinine, plasma cholesterol or hemoglobin levels. These results demonstrate that a greater than normal increase of CK plasma levels occurs in nephrotics following physical exercise, and that this increment correlates with the severity of urinary protein wasting. This suggests an increased susceptibility to muscle injury in nephrotic patients probably related to protein depletion and/or to modifications of muscle cell metabolism. Further studies are needed to define the pathogenesis of our findings.