NFL during acute spinal cord lesions in MS: a hurdle for the detection of inflammatory activity.

INTRODUCTION: Levels of neuro-filament light chain (NFL) correlate with clinical and radiological activity in multiple sclerosis (MS) and have been used as a surrogate biomarker of axonal destruction related to inflammatory activity. The main objective of this work is to explore the specific contribution of acute inflammation within the spinal cord to the elevation of NFL levels. PATIENTS AND METHODS: MS patients with a baseline study of NFL at diagnosis of the disease and a brain and spinal cord MRI scan were selected. Patients were classified according to the presence, number and location of gadolinium enhancing lesion (GEL) and the relationship between NFL levels and both brain and spinal cord GEL were explored. RESULTS: Seventy-seven patients were selected. NFL levels were significantly higher in patients with only one GEL restricted to the brain than those without GEL (1702 pg/ml vs 722.7 pg/mL, p = 0.03) and correlated with number. However, no differences were seen among patients with GEL limited to the spinal cord and those without GEL (735.2 pg/ml vs 722.7 pg/mL). CONCLUSION: Our study reaffirms the value of NFL levels in monitoring asymptomatic inflammatory activity in the brain measured by GEL. However, NFL concentration is not as useful when only inflammatory activity occurs in the spinal cord.

Protective effects of melatonin on changes occurring in the experimental autoimmune encephalomyelitis model of multiple sclerosis.

BACKGROUND: Melatonin has been related to the pathophysiology of multiple sclerosis (MS), and its anti-inflammatory and immunomodulatory properties have been proved in numerous neurodegenerative diseases. This study aimed to find out whether a melatonin supplement in MS is able to act as a benefit to its clinical status, i.e. oxidative stress, inflammation and indirect biomarkers of bacterial dysbiosis, lipopolysaccharide (LPS) and LPS-binding protein (LBP), verifying its therapeutic potential and its possible clinical use in patients with MS. METHODS: The animal MS model, experimental autoimmune encephalomyelitis (EAE), was employed whereby 25 male Dark Agouti rats (5 animals per group) were divided into: a control group (not manipulated); a control+vehicle group; a control+melatonin group; an EAE group; an EAE+melatonin group. Melatonin was administered daily for 51 days, at a dose of 1 mg/kg body weight/i.p., once a day, five days a week. RESULTS: The results from the administration of melatonin demonstrated an improvement in clinical status, a diminution in oxidative stress and inflammation, as well as in bacterial dysbiosis. CONCLUSION: Melatonin could play an effective role against MS, either alone or as a therapy combined with traditional agents.

Optimization of the magnetic field homogeneity of circular and conical coil pairs.

The magnetic field generated by a pair of coaxial circular loops is analyzed in order to find the optimum separation between the loops for each value of a prescribed homogeneity. For the maximum heterogeneities considered here, 0.1%, 1%, and 10%, the optimum loop spacing is obtained following a graphical procedure so that the length of the homogeneous field region along the axis is the longest possible. This study is extended to regions near the axis and to the entire region surrounding the center, calculating the loop separation that produces the largest homogeneous volume. The field homogeneity of a pair of "Helmholtz" coaxial conical coils is also investigated to obtain the optimum spacing between the conical coils; the volumes calculated with the desired homogeneity are compared with those obtained with a single pair of optimum coaxial loops. A new arrangement is hereby proposed based on double conical coils with optimum separation between the coils and optimum aperture of the cones. Some of the proposed arrangements are carried out in the laboratory where the experimental results are in good agreement with the theoretical predictions.

Treatment with alemtuzumab or rituximab after fingolimod withdrawal in relapsing-remitting multiple sclerosis is effective and safe.

BACKGROUND: It has been described that treating relapsing-remitting multiple sclerosis (RRMS) patients with alemtuzumab following fingolimod could be less effective due to the different dynamics of lymphocyte repopulation. Effectiveness and safety of alemtuzumab compared to rituximab after fingolimod withdrawal were analyzed. PATIENTS AND METHODS: A follow-up of a cohort of RRMS patients treated with alemtuzumab or rituximab after fingolimod withdrawal was accomplished. Effectiveness, measured by the percentage of patients with no evidence of disease activity (NEDA), and the presence of side effects (SE) were registered. RESULTS: Fifty-five patients, 28 with alemtuzumab and 27 with rituximab, were analyzed. No differences in the washout period or in the baseline lymphocytes counts were observed. After a mean follow-up period of 28.8 months, the annualized relapsing rate was significantly reduced in the alemtuzumab group from 1.29 to 0.004 (p < 0.001) and in the rituximab group from 1.24 to 0.02 (p < 0.001), without differences. A significant reduction of the median EDSS from 2.8 to 2.0 in the alemtuzumab group and from 3.5 to 2.5 (p < 0.01) in the rituximab group was observed, without differences. Eighty-two per cent (n = 28) of patients in alemtuzumab group and 69.2% (n = 26) in rituximab group achieved NEDA criteria, without differences (p = 0.3). Symptoms related to the infusion were the most frequent SE in both groups. No serious SE were registered. CONCLUSION: Treating RRMS patients with alemtuzumab or rituximab after fingolimod withdrawal is effective and safe, without significant differences between both groups in our series.

Efficacy and safety of rituximab in relapsing and progressive multiple sclerosis: a hospital-based study.

INTRODUCTION: Rituximab is considered as a potential therapeutic option in relapsing-remitting (RRMS) and progressive forms (PMS) of multiple sclerosis (MS). OBJECTIVE: To investigate the effectiveness and safety of rituximab in MS. PATIENTS AND METHODS: Observational study of effectiveness (clinical and radiological) and safety of rituximab in RRMS and PMS. RESULTS: A total of 90 rituximab-treated patients were collected: 31 RRMS and 59 PMS All patients had an active disease despite standard treatment. The annualized relapse rate (ARR) the year before rituximab was 0.86, 53.3% of patients had gadolinium enhanced lesion, and mean Expanded Disability Status Scale (EDSS) had increased from 4.2 to 4.9. During treatment, the ARR was reduced an 88.4% (p < 0.001). A significant decrease of EDSS to 4.6 was observed (p = 0.01) after 1 year of treatment, which remained stable during the second year in both groups. There was no evidence of disease activity in 70% of total sample, 74.2% of RRMS, and 67% of the PMS patients. Infusion-related symptoms were the most prevalent side effect (18.8%) and most were mild. Three thrombotic events were detected. CONCLUSION: Rituximab could be an effective and safe treatment in aggressive RRMS. Some selected PMS patients could also benefit from this treatment.

Magnetic field homogeneity of a conical coaxial coil pair.

An analytical study of the magnetic field created by a double-conical conducting sheet is presented. The analysis is based on the expansion of the magnetic field in terms of Legendre polynomials. It is demonstrated analytically that the angle of the conical surface that produces a nearly homogeneous magnetic field coincides with that of a pair of loops that fulfills the Helmholtz condition. From the results obtained, we propose an electric circuit formed by pairs of isolated conducting loops tightly wound around a pair of conical surfaces, calculating numerically the magnetic field produced by this system and its heterogeneity. An experimental setup of the proposed circuit was constructed and its magnetic field was measured. The results were compared with those obtained by numerical calculation, finding a good agreement. The numerical results demonstrate a significant improvement in homogeneity in the field of the proposed pair of conical coils compared with that achieved with a simple pair of Helmholtz loops or with a double solenoid. Moreover, a new design of a double pair of conical coils based on Braunbek's four loops is also proposed to achieve greater homogeneity. Regarding homogeneity, the rating of the analyzed configurations from best to worst is as follows: (1) double pair of conical coils, (2) pair of conical coils, (3) Braunbek's four loops, (4) Helmholtz pair, and (5) solenoid pair.

[Natalizumab and reduction of carbonylated proteins in patients with multiple sclerosis]. / Natalizumab y reduccion de los niveles de proteinas carboniladas en pacientes con esclerosis multiple.

INTRODUCTION: The sensitivity of the central nervous system to oxidative damage and its relationship with inflammatory response are well known. Recent studies have shown that oxidative stress is present in the establishment and development of multiple sclerosis (MS). One of the most recent treatments in this process is natalizumab, a monoclonal antibody. AIM: To evaluate whether the therapeutic effect of natalizumab is associated with the severity of the disease and the oxidative damage. PATIENTS AND METHODS: Researchers recruited twenty patients with relapsing-remitting MS (RRMS) undergoing therapy with natalizumab and distributed, according to the Expanded Disability Status Scale (EDSS), in two groups: RRMS-1 (EDSS < 5) and RRMS-2 (EDSS ≥ 5). Blood samples were taken for an oxidative profile study. RESULTS: Data showed a decrease in carbonylated proteins following treatment with natalizumab. The reduction in oxidative damage rated as protein oxidation is significant between the previous (baseline) situation of the patient and after 14 months' treatment. The most significant decrease coincided with the patients with the highest levels of severity in the process. Although it has not been possible to establish a correlation, the statistical significance is higher for patients in the RRMS-2 group treated with natalizumab. The antioxidant systems, on the other hand, did not display any statistically significant changes. CONCLUSIONS: Natalizumab brings about a reduction in carbonylated protein levels.

Neuroprotective effects of extremely low-frequency electromagnetic fields on a Huntington's disease rat model: effects on neurotrophic factors and neuronal density.

There is evidence to suggest that the neuroprotective effect of exposure of extremely low-frequency electromagnetic fields (ELF-EMF) may be due, at least in part, to the effect of these fields on neurotrophic factors levels and cell survival, leading to an improvement in behavior. This study was undertaken to investigate the neuroprotective effects of ELFEF in a rat model of 3-nitropropionic acid (3NP)-induced Huntington's disease. Behavior patterns were evaluated, and changes in neurotrophic factor, cell damage, and oxidative stress biomarker levels were monitored in Wistar rats. Rats were given 3NP over four consecutive days (20 mg/kg body weight), whereas ELFEF (60 Hz and 0.7 mT) was applied over 21 days, starting after the last injection of 3NP. Rats treated with 3NP exhibited significantly different behavior in the open field test (OFT) and the forced swim test (FST), and displayed significant differences in neurotrophic factor levels and oxidative stress biomarkers levels, together with a neuronal damage and diminished neuronal density, with respect neuronal controls. ELFEF improved neurological scores, enhanced neurotrophic factor levels, and reduced both oxidative damage and neuronal loss in 3NP-treated rats. ELFEF alleviates 3NP-induced brain injury and prevents loss of neurons in rat striatum, thus showing considerable potential as a therapeutic tool.

Straightforward estimation of the elastic constants of an isotropic cube excited by a single percussion.

Ritz's method is applied to calculate accurate values of the lowest non-dimensional natural frequencies of a freely vibrating isotropic cube. The dependence of such frequencies and their quotients on Poisson's ratio is established. Vibration of a cube caused by percussion is detected at a point by a laser interferometer. With the help of the tables and graphs provided and with the values of the first lowest frequencies obtained experimentally in a single test, Poisson's ratio and the shear modulus are calculated by means of elementary arithmetical operations.

[Tuberculosis in the area of Lorca: to adapt or resist]. / Tuberculosis en la comarca de Lorca: adaptarse o resistir.

OBJECTIVE: We studied the epidemiological characteristic of tuberculosis in Lorca area, drug resistant and the effect of the immigration population (Ecuador) in this area. PATIENTS AND METHODS: A retrospective study for six years ago (1999, January to 2004, December) was realized. Epidemiological data, initial diagnostic probability, mycobacteria stain and cultive, drug resistance, treatment response, and epidemiological differences between immigrants and spain population were compared. RESULTS: Within 158 cases registered, 41.7 percent were immigrants with less than one year in Spain, the most part Ecuador population. We observed that extrapulmonar tuberculosis was lower initial diagnostic probability than pleural disease as well too haemoptisis, pleural pain and weight loss. It was identified positive micobacterial stain in 35.4 percent of respiratory samples. It was successfully results in 74 percent of cases and 13.9 percent of patients were lost, this result was frequently registered in immigrants, The isoniazide resistant in patients with not previous treatment was 5.3 percent and it was 9.5 percent in immigrants and 10.8 percent in Ecuador population. CONCLUSION: It is necessary improve: the diagnostic of extrapulmonar tuberculosis and avoid loss patient by programs of capture and then the successfully treatments raise. The isoniazide resistant in this area suggest that we must use initial four drug than tree and this manner not raise the drug resistant in the area.

Morphogenesis of rat experimental pulmonary emphysema induced by intratracheally administered papain: changes in elastic fibres.

The ultrastructural changes of elastic fibres in emphysematous lungs have been studied in men, but few works exist on this topic in experimental emphysematous animals. In this paper, the morphogenesis of emphysema and alterations of the elastic fibres produced by the instillation of papain are described by light and electron microscopy. Wistar rats were instilled through the trachea with papain at a rate of 3 mg/100 g animal weight. The animals were sacrificed 12 h, 3 days, 10 days and 60 days after enzyme instillation. The "Mean Linear Intercept" (MLI), the "Number of fenestrations/respiratory units" (NF) the "Number of macrophages per mm of alveolar wall" (NM) and the "Number of respiratory unit/mm2" (RU), both in the control and experimental groups were studied. Two months after treatment, the experimental group showed a strong increase in the MLI (p<0.001) and NF (p<0.001), and a diminished number of RU (p<0.05) compared with the control group. Partial correlation analysis showed a positive correlation only between MLI and NF. Twelve hours after papain instillation an inflammatory response was observed, the elastic fibres were ruptured, while the microfibrilar component remained. New formations of eulanin elastic fibres were observed three days post papain instillation. After ten days the interalveolar oedema had disappeared and the elastic fibres were of normal morphology although irregular groups of strips of elastic fibres were evident. A mixed pattern of panlobular, centrilobular and normal lung zones were observed. Two months after papain instillation abundant accumulations of elastic fibres of irregular outline were observed associated to collagen fibres. In conclusion, the morphometric parameters studied showed a significant progression of the emphysema. The strong correlation between NF and MLI suggested that papain-induced emphysema is principally caused by breaches of the alveolar walls. The results seem to point to a very abnormal remodelling process associated with elastic fibre regeneration, although there were no signs of destruction of these new fibres formed in emphysematous rat lung induced by papain.

Influence of residency training on personal stress and impairment in family life: analysis of related factors.

OBJECTIVES: This cross-sectional study was designed to assess the level of stress among residents and stress-related impairment of family life. SUBJECTS AND METHODS: A 41-item anonymous questionnaire was designed to determine the level of stress and its effects on the residents' family as well as factors associated with stress during residency training in a tertiary-care hospital accredited with official resident training 'Medicos Internos Residentes' in Murcia, Spain. Questionnaires were distributed in sealed nominal envelopes during February and March 2002 to 227 eligible residents. RESULTS: Of the 227 residents, 175 (77%) completed and returned the questionnaires. Forty-two percent of residents recognized that residency training caused an important level of stress and 21% felt that stress interfered with family relationships. Both factors were significantly associated. Feelings of being unsatisfied with supervision of care and achievement of training objectives as well as low satisfaction with residency training and poor assessment of the hospital were significant stressors. Impairment in family life was significantly dependent on degree of satisfaction with residency training and evaluation of the hospital. CONCLUSION: The data showed that residency training generated stress and impaired family life. These were closely associated with perception of being unsatisfied with the residency training and evaluation.

Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5-week randomized, double-blind, placebo-controlled trial.

OBJECTIVE: The aim of the present study is to investigate the effect of antioxidant polyphenol-rich pomegranate juice (PJ) supplementation for 5 weeks on patients with stable chronic obstructive pulmonary disease (COPD), since the oxidative stress plays a major role in the evolution and pathophysiology of COPD. DESIGN: A randomized, double-blind, placebo-controlled trial was conducted. SUBJECTS: A total of 30 patients with stable COPD were randomly distributed in two groups (15 patients each). INTERVENTIONS: Both groups consumed either 400 ml PJ daily or matched placebo (synthetic orange-flavoured drink) for 5 weeks. Trolox Equivalent Antioxidant Capacity (TEAC) of PJ, blood parameters (14 haematological and 18 serobiochemical), respiratory function variables, bioavailability of PJ polyphenols (plasma and urine) and urinary isoprostane (8-iso-PGF(2alpha)) were evaluated. RESULTS: The daily dose of PJ (containing 2.66 g polyphenols) provided 4 mmol/l TEAC. None of the polyphenols present in PJ were detected in plasma or in urine of volunteers. The most abundant PJ polyphenols, ellagitannins, were metabolized by the colonic microflora of COPD patients to yield two major metabolites in both plasma and urine (dibenzopyranone derivatives) with no TEAC. No differences were found (P > 0.05) between PJ and placebo groups for any of the parameters evaluated (serobiochemical and haematological), urinary 8-iso-PGF(2alpha), respiratory function variables and clinical symptoms of COPD patients. CONCLUSIONS: Our results suggest that PJ supplementation adds no benefit to the current standard therapy in patients with stable COPD. The high TEAC of PJ cannot be extrapolated in vivo probably due to the metabolism of its polyphenols by the colonic microflora. The understanding of the different bioavailability of dietary polyphenols is critical before claiming any antioxidant-related health benefit. SPONSORSHIP: 'Fundación Séneca' (Murcia, Spain), Project PB/18/FS/02 and Spanish CICYT, Project AGL2003-02195.

Cold urticaria associated with acute serologic toxoplasmosis.

Cold urticaria is defined as a urticarial and/or angioedematous reaction of the skin to contact with cold objects, water or air. Types of urticaria associated with infectious diseases, such as mononucleosis, rubeola, varicella, syphilis, hepatitis, and HIV infection have been reported. We present the case of a patient who developed cold urticaria associated with acute serologic toxoplasmosis. The patient was a 34-year-old man who for the previous 2 months had presented cutaneous pruritus accompanied by several papular lesions in parts of the skin exposed to cold as well as those in contact with cold water. The result of an "ice-cube test" was positive. Serologic tests for Toxoplasma gondii showed an IgG level of 68 UI/ml and were positive for IgM, while a test for cryoglobulins was positive. One month later cryoglobulins were negative and a serologic test for T. gondii showed an IgG concentration of 75 UI/ml and positive IgM. Three months later cryoglobulins were still negative, IgG for T. gondii was 84 UI/ml, and IgM was positive. After 6 months cryoglobulins were still negative, IgG level was 68 UI/ml and IgM was still slightly positive. In the final evaluation, 14 months later, IgG level was 32 UI/ml and IgM was negative. The patient continues to present clinical manifestations of cold urticaria, although he has experienced some improvement and his tolerance to cold has increased after treatment with cetirizine.

Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome.

OBJECTIVE: To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1. METHODS: A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured. RESULTS: The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides. CONCLUSIONS: Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.

[Scintigraphic study of gastric emptying of rehydration drinks in athletes]. / Estudio gammagráfico del ritmo de vaciado gástrico de bebidas de reposición en deportistas.

UNLABELLED: This study aims to evaluate how rehydration beverage ingestion influences gastric emptying rate (in cycle ergometer) at rest and during exercise at 70 % of maximal oxygen consumption (VO2max). MATERIAL AND METHOD: 26 well-trained cyclists performed a preliminary maximal test until exhaustion to evaluate their VO2max, and two submaximal exercise tests at 70 % of their mode-specific VO2max. Each test was separated by one week. During the two submaximal tests, cyclists consumed 200 ml of a 99mTc-DTPA labeled rehydration beverage (A or B) and scintigraphy determinations were performed at rest. After, exercise was initiated for 60 minutes with an intake rate of 200 ml every 15 minutes, making gastric serial scintigraphy determinations. The difference regarding chemical composition between A and B drinks resides in the fact that drink A contains a smaller load in carbohydrates (10.3 g/100 ml versus 15.2 g/100 ml of B), proteins in form of serum milk and antioxidants in form of fruit juice. Both contain ions and vitamins. RESULTS: at rest, gastric count number was significantly reduced (p > 0.000) from 0 to 25 minutes for both A and B beverage. At the end of exercise (60 min), there was greater gastric retention for B beverage than for A, this difference being statistically significant (p < 0.031). CONCLUSIONS: The A beverage, a rehydration drink on the market with protein and antioxidants with fruit juice content, has a faster gastric emptying rate than the B sport beverage.

Research training during medical residency (MIR). Satisfaction questionnaire.

INTRODUCTION: It is during Medical Residency Training (MIR) that knowledge, abilities and habits are acquired, which will shape professional activity in the future. It is therefore very likely that residents who do not acquire the necessary habits and knowledge for research activities will eventually not carry out these activities in the future. The aim of this study was to analyze the level of satisfaction of residents with his or her scientific and research training, and to determine any deficiencies with respect to this training. MATERIALS AND METHODS: The aim of the questionnaire used was to determine the level of satisfaction of residents regarding their scientific and research training during their residency period. Questionnaires were usually distributed via internal mail to all residents (MIR physicians) registered at a third level teaching hospital, with a completion rate of 78% (n = 178). RESULTS: As far as the evaluation of scientific training is concerned, 68% of residents were dissatisfied or very dissatisfied. With respect to scientific studies carried out, 49% of residents had not taken part in any, but the number of studies carried out increases as the residency progresses. On the other hand, 22% of residents reported not having started their doctoral thesis, 50% having attended doctorate courses, 24% having a title for their thesis, and only 4% having written a thesis. Doctorate courses, thesis topics, and written theses increase with the year of residency, and a greater activity may be seen in this respect in surgical departments. If we analyze help available to residents for their carrying out scientific activities, 55% reported that only selected assistant doctors would offer help, and 21% reported that no doctors would offer help. Dissatisfaction with research training increases with the year of residency. With regard to main specialist fields, it can be seen that residents in surgical fields carry out more theses, whereas central fields report less facilities. Finally, if we evaluate the influence that these variables may have on the general satisfaction of residents with his or her residency, these variables are seen to be significant factors of dissatisfaction. CONCLUSIONS: Most residents are dissatisfied with their scientific training and have relatively few facilities for developing such skills, which in turn results in a scarce number of scientific studies and doctoral theses.