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2.
Br Med Bull ; 146(1): 43-72, 2023 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-37170956

RESUMEN

INTRODUCTION: Whole-body cryotherapy (WBC) is a controlled exposure of the whole body to cold to gain health benefits. In recent years, data on potential applications of WBC in multiple clinical settings have emerged. SOURCES OF DATA: PubMed, EBSCO and Clinical Key search using keywords including terms 'whole body', 'cryotherapy' and 'cryostimulation'. AREAS OF AGREEMENT: WBC could be applied as adjuvant therapy in multiple conditions involving chronic inflammation because of its potent anti-inflammatory effects. Those might include systemic inflammation as in rheumatoid arthritis. In addition, WBC could serve as adjuvant therapy for chronic inflammation in some patients with obesity. AREAS OF CONTROVERSY: WBC probably might be applied as an adjuvant treatment in patients with chronic brain disorders including mild cognitive impairment and general anxiety disorder and in patients with depressive episodes and neuroinflammation reduction as in multiple sclerosis. WBC effects in metabolic disorder treatment are yet to be determined. WBC presumably exerts pleiotropic effects and therefore might serve as adjuvant therapy in multi-systemic disorders, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). GROWING POINTS: The quality of studies on the effects of WBC in the clinical setting is in general low; hence, randomized controlled trials with adequate sample size and longer follow-up periods are needed. AREAS ARE TIMELY FOR DEVELOPING RESEARCH: Further studies should examine the mechanism underlying the clinical efficacy of WBC. Multiple conditions might involve chronic inflammation, which in turn could be a potential target of WBC. Further research on the application of WBC in neurodegenerative disorders, neuropsychiatric disorders and ME/CFS should be conducted.


Asunto(s)
Síndrome de Fatiga Crónica , Humanos , Síndrome de Fatiga Crónica/terapia , Crioterapia , Enfermedad Crónica , Resultado del Tratamiento , Inflamación/metabolismo
3.
Cryobiology ; 112: 104546, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37230457

RESUMEN

In the previous study, whole-body cryotherapy (WBC)+static stretching (SS) has been shown to reduce the severity of some symptoms in Chronic Fatigue Syndrome (CFS) noted just after the therapy. Here we consider the effects of treatment and explore the sustainability of symptom improvements at four weeks (one-month) follow-up. Twenty-two CFS patients were assessed one month after WBC + SS programme. Parameters related to fatigue (Chalder Fatigue Questionnaire (CFQ), Fatigue Impact Scale (FIS), Fatigue Severity Scale (FSS)), cognitive function (Trial Making test part A and B (TMT A and TMT B and its difference (TMT B-A)), Coding) hemodynamic, aortic stiffness (aortic systolic blood pressure (sBP aortic)) and autonomic nervous system functioning were measured. TMT A, TMT B, TMT B-A and Coding improved at one month after the WBC + SS programme. WBC + SS had a significant effect on the increase in sympathetic nervous system activity in rest. WBC + SS had a significant, positive chronotropic effect on the cardiac muscle. Peripheral and aortic systolic blood pressure decreased one month after WBC + SS in comparison to before. Effects of WBC + SS on reduction of fatigue, indicators of aortic stiffness and symptoms severity related to autonomic nervous system disturbance and improvement in cognitive function were maintained at one month. However, improvement in all three fatigue scales (CFQ, FIS and FSS) was noted in 17 of 22 patients. In addition, ten patients were treated initially but they were not assessed at 4 weeks, and are thus not included in the 22 patients who were examined on follow-up. The overall effects of WBC + SS noted at one month post-treatment should be interpreted with caution.


Asunto(s)
Síndrome de Fatiga Crónica , Ejercicios de Estiramiento Muscular , Humanos , Crioterapia , Síndrome de Fatiga Crónica/terapia , Encuestas y Cuestionarios
4.
J Transl Med ; 20(1): 273, 2022 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-35715857

RESUMEN

BACKGROUND: The aim of this study was to explore the tolerability and effect of static stretching (SS) and whole body cryotherapy (WBC) upon fatigue, daytime sleepiness, cognitive functioning and objective and subjective autonomic nervous system functioning in those with Chronic Fatigue Syndrome (CFS) compared to a control population. METHODS: Thirty-two CFS and eighteen healthy controls (HC) participated in 2 weeks of a SS + WBC programme. This programme was composed of five sessions per week, 10 sessions in total. RESULTS: A significant decrease in fatigue was noted in the CFS group in response to SS + WBC. Some domains of cognitive functioning (speed of processing visual information and set-shifting) also improved in response to SS + WBC in both CFS and HC groups. Our study has confirmed that WBC is well tolerated by those with CFS and leads to symptomatic improvements associated with changes in cardiovascular and autonomic function. CONCLUSIONS: Given the preliminary data showing the beneficial effect of cryotherapy, its relative ease of application, good tolerability, and proven safety, therapy with cold exposure appears to be an approach worth attention. Further studies of cryotherapy as a potential treatment in CFS is important in the light of the lack of effective therapeutic options for these common and often disabling symptoms.


Asunto(s)
Síndrome de Fatiga Crónica , Ejercicios de Estiramiento Muscular , Sistema Nervioso Autónomo , Crioterapia , Síndrome de Fatiga Crónica/diagnóstico , Frecuencia Cardíaca/fisiología , Humanos
5.
Neurol Sci ; 43(8): 4829-4839, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35507192

RESUMEN

OBJECTIVES: This study evaluates cardiovascular autonomic dysfunction (CAD) in multiple sclerosis (MS) and explores if CAD is related to clinical outcomes and fatigue severity. METHODS: A total of 53 MS patients (30 relapsing-remitting, RRMS; 23 progressive, PMS) and 30 healthy controls were evaluated. TaskForce® Monitor was used to assess impedance cardiography parameters, heart rate (HRV), and blood pressure (BPV) variability during head-up tilt test (HUTT). Expiration/inspiration (E/I) ratio was assessed in response to a deep breathing test. Fatigue severity was evaluated using Chalder Fatigue Scale (CFQ). RESULTS: Compared to controls, PMS patients were characterized by increased sympathetic-parasympathetic ratio at rest (p < 0.01), decreased resting values of parasympathetic parameters (high-frequency HRV, p < 0.05; E/I ratio, p < 0.001), and index of contractility (p < 0.05), whereas RRMS patients showed reduced E/I ratio (p < 0.01). Compared to RRMS group, PMS patients had higher sympathovagal ratio and lower cardiac inotropy parameters (p < 0.05). No intergroup differences were observed for cardiovascular and autonomic function test parameters after HUTT. PMS and low CFQ physical score were identified as independent predictors of sympathetic hyper-reactivity as measured with HRV. Greater disability and male sex were predictors of diastolic BP increase and reduced cardiac inotropy parameters, and older age was predictor of decreased vagal tone (E/I ratio, high-frequency HRV). CONCLUSION: Cardiovascular autonomic modulation is altered in MS and highly dependent on disease variant, disability level, fatigue severity, and patients' demographics.


Asunto(s)
Enfermedades del Sistema Nervioso Autónomo , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Sistema Nervioso Autónomo , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Presión Sanguínea , Fatiga/etiología , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple Recurrente-Remitente/complicaciones
6.
J Therm Biol ; 96: 102861, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33627288

RESUMEN

In this review we examine studies exploring the effects of whole-body cryostimulation (WBC) from the perspective of applications with age with subjects over the age of 55 years old. Blood based factors such as Erythropoietin and Il-3 increased in exercised trained and normal subjects after WBC while other parameters did not change. WBC treatment of patients with Rheumatoid Arthritis decreased levels of the inflammatory markers IL-6 and TNF-α with a in the elasticity of erythrocytes. In older subjects with Mild Cognitive Impairment (MCI) a significant improvement of short-term memory was noted with reduced levels of IL-6 with an increase in BDNF release when whole blood was challenged with Aß42. WBC appears to be an exciting non-pharmacological treatments with pleiotropic action. It has potential in enhancing performance and alleviating chronic conditions in older subjects as part of an active rest programme in combination with regular physical exercise. In conditions associated with cognitive dysfunction including Alzheimer's and other forms of dementia the many properties of WBC as an affordable treatment has exciting therapeutic potential.


Asunto(s)
Envejecimiento , Crioterapia , Humanos
7.
Medicina (Kaunas) ; 57(10)2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34684049

RESUMEN

This collection of research papers addresses fundamental questions concerning the nature of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS), the problem of disbelief and lack of knowledge and understanding of the condition among many doctors and the origins of this problem, and its impact on patients and their families. We report briefly the growing knowledge of the underlying pathological processes in ME/CFS, and the development of new organizations, including Doctors with ME, the US ME/CFS Clinical Coalition and EUROMENE, to address aspects of the challenges posed by the illness. We discuss the implications of COVID-19, which has much in common with ME/CFS, with much overlap of symptoms, and propose a new taxonomic category, which we are terming post-active phase of infection syndromes (PAPIS) to include both. This collection of papers includes a number of papers reporting similar serious impacts on the quality of life of patients and their families in various European countries. The advice of EUROMENE experts on diagnosis and management is included in the collection. We report this in light of guidance from other parts of the world, including the USA and Australia, and in the context of current difficulties in the UK over the promulgation of a revised guideline from the National Institute for Health and Care Excellence (NICE). We also consider evidence on the cost-effectiveness of interventions for ME/CFS, and on the difficulties of determining the costs of care when a high proportion of people with ME/CFS are never diagnosed as such. The Special Issue includes a paper which is a reminder of the importance of a person-centred approach to care by reviewing mind-body interventions. Finally, another paper reviews the scope for prevention in minimizing the population burden of ME/CFS, and concludes that secondary prevention, through early detection and diagnosis, could be of value.


Asunto(s)
COVID-19 , Síndrome de Fatiga Crónica , Europa (Continente) , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/terapia , Humanos , Calidad de Vida , SARS-CoV-2
8.
Medicina (Kaunas) ; 57(3)2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33652622

RESUMEN

The potential benefits of the scientific insights gleaned from years of treating ME/CFS for the emerging symptoms of COVID-19, and in particular Longhaul- or Longhauler-COVID-19 are discussed in this opinion article. Longhaul COVID-19 is the current name being given to the long-term sequelae (symptoms lasting beyond 6 weeks) of SARS-CoV-2 infection. Multiple case definitions for ME/CFS exist, but post-exertional malaise (PEM) is currently emerging as the 'hallmark' symptom. The inability to identify a unique trigger of ME/CFS, as well as the inability to identify a specific, diagnostic laboratory test, led many physicians to conclude that the illness was psychosomatic or non-existent. However, recent research in the US and the UK, championed by patient organizations and their use of the internet and social media, suggest underlying pathophysiologies, e.g., oxidative stress and mitochondrial dysfunction. The similarity and overlap of ME/CFS and Longhaul COVID-19 symptoms suggest to us similar pathological processes. We put forward a unifying hypothesis that explains the precipitating events such as viral triggers and other documented exposures: For their overlap in symptoms, ME/CFS and Longhaul COVID-19 should be described as Post Active Phase of Infection Syndromes (PAPIS). We further propose that the underlying biochemical pathways and pathophysiological processes of similar symptoms are similar regardless of the initiating trigger. Exploration of the biochemical pathways and pathophysiological processes should yield effective therapies for these conditions and others that may exhibit these symptoms. ME/CFS patients have suffered far too long. Longhaul COVD-19 patients should not be subject to a similar fate. We caution that failure to meet the now combined challenges of ME/CFS and Longhaul COVID-19 will impose serious socioeconomic as well as clinical consequences for patients, the families of patients, and society as a whole.


Asunto(s)
COVID-19/complicaciones , Síndrome de Fatiga Crónica/virología , SARS-CoV-2 , Humanos , Tiempo
9.
Medicina (Kaunas) ; 57(5)2021 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-34069603

RESUMEN

Designed by a group of ME/CFS researchers and health professionals, the European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE) has received funding from the European Cooperation in Science and Technology (COST)-COST action 15111-from 2016 to 2020. The main goal of the Cost Action was to assess the existing knowledge and experience on health care delivery for people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) in European countries, and to enhance coordinated research and health care provision in this field. We report our findings and make recommendations for clinical diagnosis, health services and care for people with ME/CFS in Europe, as prepared by the group of clinicians and researchers from 22 countries and 55 European health professionals and researchers, who have been informed by people with ME/CFS.


Asunto(s)
Síndrome de Fatiga Crónica , Consenso , Atención a la Salud , Europa (Continente) , Síndrome de Fatiga Crónica/diagnóstico , Síndrome de Fatiga Crónica/epidemiología , Síndrome de Fatiga Crónica/terapia , Humanos
10.
Sensors (Basel) ; 20(7)2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32272729

RESUMEN

The primary means for electronic position fixing currently in use in majority of contemporary merchant ships are shipborne GPS (Global Positioning System) receivers or DGPS (Differential GPS) and IALA (International Association of Lighthouse Authorities) radio beacon receivers. More advanced GNSS (Global Navigation Satellite System) receivers able to process signals from GPS, Russian GLONASS, Chinese Beidou, European Galileo, Indian IRNSS, Japan QZSS, and satellite-based augmentation systems (SBAS), are still relatively rare in maritime domain. However, it is expected that such combined or multi-system receivers will soon become more common in maritime transport and integrated with gyro, inertial, radar, laser, and optical sensors, and they will become indispensable onboard maritime autonomous surface ships (MASS). To be prepared for a malfunction of any position sensors, their state-of-the-art integrity monitoring should be developed and standardized, taking into account the specificity of MASS and e-navigation safety. The issues of existing requirements, performance standards, and future concepts of integrity monitoring for maritime position sensors are discussed and presented in this paper.

11.
Sensors (Basel) ; 20(6)2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32188114

RESUMEN

Wearable systems constitute a promising solution to the emerging challenges of healthcare provision, feeding machine learning frameworks with necessary data. In practice, however, raw data collection is expensive in terms of energy, and therefore imposes a significant maintenance burden to the user, which in turn results in poor user experience, as well as significant data loss due to improper battery maintenance. In this paper, we propose a framework for on-board activity classification targeting severely energy-constrained wearable systems. The proposed framework leverages embedded classifiers to activate power-hungry sensing elements only when they are useful, and to distil the raw data into knowledge that is eventually transmitted over the air. We implement the proposed framework on a prototype wearable system and demonstrate that it can decrease the energy requirements by one order of magnitude, yielding high classification accuracy that is reduced by approximately 5%, as compared to a cloud-based reference system.


Asunto(s)
Técnicas Biosensibles , Aprendizaje Automático , Dispositivos Electrónicos Vestibles , Suministros de Energía Eléctrica , Humanos
12.
Medicina (Kaunas) ; 56(4)2020 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-32290164

RESUMEN

Background and objective: This is the first study to investigate the effect of high-flow oxygen therapy, using a normobaric chamber on cognitive, biochemical (oxidative stress parameters and the level of neurotrophins), cardiovascular and autonomic functioning. Materials and methods: 17 healthy volunteers, eight males and nine females, with a mean age of 37.5 years, were examined. The experimental study involved ten two-hour exposures in a normobaric chamber with a total pressure of 1500 hPa, in air adjusted to 37% oxygen, 1.079% carbon dioxide and 0.44% hydrogen. Cognitive function was assessed by using Trail Making Test parts A, B and difference in results of these tests (TMT A, TMT B and TMT B-A); California Verbal Learning Test (CVLT); Digit symbol substitution test (DSST); and Digit Span (DS). Fatigue (Fatigue Severity Scale (FSS)), cardiovascular, autonomic and baroreceptor functioning (Task Force Monitor) and biochemical parameters were measured before and after intervention. Results: After 10 sessions in the normobaric chamber, significant decreases in weight, caused mainly by body fat % decrease (24.86 vs. 23.93%, p = 0.04 were observed. TMT part A and B results improved (p = 0.0007 and p = 0.001, respectively). In contrast, there was no statistically significant influence on TMT B-A. Moreover, decrease in the number of symbols left after a one-minute test in DSST was noted (p = 0.0001). The mean number of words correctly recalled in the CVLT Long Delay Free Recall test improved (p = 0.002), and a reduction in fatigue was observed (p = 0.001). Biochemical tests showed a reduction in levels of malondialdehyde (p < 0.001), with increased levels of Cu Zn superoxide dismutase (p < 0.001), Neurotrophin 4 (p = 0.0001) and brain-derived neurotrophic factor (p = 0.001). A significant increase in nitric oxide synthase 2 (Z = 2.29, p = 0.02) and Club cell secretory protein (p = 0.015) was also noted. Baroreceptor function was significantly improved after normobaric exposures (p = 0.003). Significant effect of normobaric exposures and BDNF in CVLT Long Delay Free Recall was noted. Conclusions: This study demonstrates that 10 exposures in a normobaric chamber have a positive impact on visual information and set-shifting processing speed and increase auditory-verbal short-term memory, neurotrophic levels and baroreceptor function. A response of the respiratory tract to oxidative stress was also noted. There is a need to rigorously examine the safety of normobaric therapy. Further studies should be carried out with physician examination, both pre and post treatment.


Asunto(s)
Fármacos del Sistema Nervioso Autónomo/metabolismo , Cognición/fisiología , Voluntarios Sanos/estadística & datos numéricos , Hiperoxia/complicaciones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas/estadística & datos numéricos , Oxígeno/administración & dosificación , Oxígeno/uso terapéutico , Polonia
13.
J Hepatol ; 70(6): 1203-1213, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30769007

RESUMEN

BACKGROUND & AIMS: Cardiovascular disease is the principle cause of death in patients with elevated liver fat unrelated to alcohol consumption, more so than liver-related morbidity and mortality. The aim of this study was to evaluate the relationship between liver fat and cardiac and autonomic function, as well as to assess how impairment in cardiac and autonomic function is influenced by metabolic risk factors. METHODS: Cardiovascular and autonomic function were assessed in 96 sedentary individuals: i) non-alcoholic fatty liver disease (NAFLD) (n = 46, hepatic steatosis >5% by magnetic resonance spectroscopy), ii) Hepatic steatosis and alcohol (dual aetiology fatty liver disease [DAFLD]) (n = 16, hepatic steatosis >5%, consuming >20 g/day of alcohol) and iii) CONTROL (n = 34, no cardiac, liver or metabolic disorders, <20 g/day of alcohol). RESULTS: Patients with NAFLD and DAFLD had significantly impaired cardiac and autonomic function when compared with controls. Diastolic variability and systolic variability (LF/HF-sBP [n/1]; 2.3 (1.7) and 2.3 (1.5) vs. 3.4 (1.5), p <0.01) were impaired in patients with NAFLD and DAFLD when compared to controls, with DAFLD individuals showing a decrease in diastolic variability relative to NAFLD patients. Hepatic steatosis and fasting glucose were negatively correlated with stroke volume index. Fibrosis stage was significantly negatively associated with mean blood pressure (r = -0.47, p = 0.02), diastolic variability (r = -0.58, p ≤0.01) and systolic variability (r = -0.42, p = 0.04). Hepatic steatosis was independently associated with cardiac function (p ≤0.01); TNF-α (p ≤0.05) and CK-18 (p ≤0.05) were independently associated with autonomic function. CONCLUSION: Cardiac and autonomic impairments appear to be dependent on level of liver fat, metabolic dysfunction, inflammation and fibrosis staging, and to a lesser extent alcohol intake. Interventions should be sought to moderate the excess cardiovascular risk in patients with NAFLD or DAFLD. LAY SUMMARY: Increased levels of fat in the liver impair the ability of the cardiovascular system to work properly. The amount of fat in the liver, metabolic control, inflammation and alcohol are all linked to the degree that the cardiovascular system is affected.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Hígado Graso/fisiopatología , Corazón/fisiopatología , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Hígado Graso/complicaciones , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/fisiopatología
14.
Medicina (Kaunas) ; 55(6)2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31159275

RESUMEN

Background and Objectives: Determining the clinical course of multiple sclerosis (MS) and prediction of long-term disability can be a big challenge. To determine early clinical features of MS, their influence on long-term disability progression, and time to transition from relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS), a cohort of Polish patients was studied. Materials and Methods: We retrospectively evaluated 375 Polish MS patients based on data from available medical records. We assessed early clinical MS features and the relationship between demographics and time from disease onset to attainment of 4 and 6 points on the Expanded Disability Status Scale (EDSS), as well as time to conversion from RRMS to SPMS. Results: The differences between initial MS variants were significantly associated with gender, age at disease onset, number and type of the first symptoms, and rate of the disability accrual. Mean times from disease onset to attainment of EDSS 4 and 6 were significantly influenced by the disease variant, age at onset, gender, degree of recovery from the initial symptoms, and first inter-bouts interval. The mean time to secondary progression was significantly influenced by the number and type of the first symptoms of RRMS. Conclusions: Early clinical features of MS are important in determining the disease variant, the time to transition from RRMS to SPMS, as well as predicting the disability accumulation of patients. Despite the small differences regarding the first MS symptoms, the disability outcomes in the cohort of Polish patients are similar to other regions of the world.


Asunto(s)
Personas con Discapacidad , Esclerosis Múltiple Crónica Progresiva/clasificación , Esclerosis Múltiple Recurrente-Remitente/clasificación , Esclerosis Múltiple/fisiopatología , Factores de Tiempo , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/clasificación , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Polonia
15.
Br Med Bull ; 128(1): 61-74, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30418540

RESUMEN

Introduction: The majority of chronic diseases are accompanied by symptoms of more or less pronounced dysautonomia, which frequently and noticeably deteriorate the quality of patients' life. Sources of data: Pubmed. Areas of agreement: Functional disorders in the autonomic nervous system (ANS) require very precise diagnostics; frequently involving several specialists and a number of diagnostic tests. Areas of controversy: Dysautonomia symptoms are of a very discrete nature and may develop much earlier than symptoms specific for a given chronic disease, significantly influencing the treatment process itself. Growing points: ANS dysfunctions should be considered at each stage of the diagnostic and treatment processes, as a predictor for the patient's clinical condition. Areas timely for developing research: Many researchers indicate that a decrease in dysautonomia intensity has a direct effect on the progress of the underlying disease and undoubtedly contributes to the improvement of the general health condition or to symptoms remission.


Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Enfermedad Crónica , Disautonomías Primarias , Humanos , Disautonomías Primarias/fisiopatología , Calidad de Vida
16.
Lancet Oncol ; 18(4): 473-485, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-28283282

RESUMEN

BACKGROUND: Clusterin is a chaperone protein associated with treatment resistance and upregulated by apoptotic stressors such as chemotherapy. Custirsen is a second-generation antisense oligonucleotide that inhibits clusterin production. The aim of the SYNERGY trial was to investigate the effect of custirsen in combination with docetaxel and prednisone on overall survival in patients with metastatic castration-resistant prostate cancer. METHODS: SYNERGY was a phase 3, multicentre, open-label, randomised trial set at 134 study centres in 12 countries. Patients were eligible for participation if they had: metastatic castration-resistant prostate cancer and had received no previous chemotherapy; prostate-specific antigen greater than 5 ng/mL; and a Karnofsky performance score of 70% or higher. Patients were randomly assigned 1:1 centrally to either the docetaxel, prednisone, and custirsen combination or docetaxel and prednisone alone. Patients were not masked to treatment allocation. Randomisation was stratified by opioid use for cancer-related pain and radiographic evidence of progression. All patients received docetaxel 75 mg/m2 intravenously with 5 mg of prednisone orally twice daily. Patients assigned docetaxel, prednisone, and custirsen received weekly doses of custirsen 640 mg intravenously after three loading doses of 640 mg. The primary endpoint was overall survival analysed in the intention-to-treat population. Patients who received at least one study dose were included in the safety analysis set. This trial is registered with ClinicalTrials.gov, number NCT01188187. The trial is completed and final analyses are reported here. FINDINGS: Between Dec 10, 2010, and Nov 7, 2012, 1022 patients were enrolled to the trial, of whom 510 were assigned docetaxel, prednisone, and custirsen and 512 were allocated docetaxel and prednisone. No difference in overall survival was recorded between the two groups (median survival 23·4 months [95% CI 20·9-24·8] with docetaxel, prednisone, and custirsen vs 22·0 months [19·5-24·0] with docetaxel and prednisone; hazard ratio [HR] 0·93, 95% CI 0·79-1·10; p=0·415). The most common adverse events of grade 3 or worse in the docetaxel, prednisone and custirsen group (n=501) compared with the docetaxel and prednisone alone group (n=499) were neutropenia (grade 3, 63 [13%] vs 28 [6%]; grade 4, 98 [20%] vs 77 [15%]), febrile neutropenia (grade 3, 52 [10%] vs 31 [6%]; grade 4, four [1%] vs two [<1%]), and fatigue (grade 3, 53 [11%] vs 41 [8%]; grade 4, three [1%] vs one [<1%]). One or more serious adverse events were reported for 214 (43%) of 501 patients treated with docetaxel, prednisone, and custirsen and 181 (36%) of 499 receiving docetaxel and prednisone alone. Adverse events were attributable to 23 (5%) deaths in the docetaxel, prednisone, and custirsen group and 24 (5%) deaths in the docetaxel and prednisone alone group. INTERPRETATION: Addition of custirsen to first-line docetaxel and prednisone was reasonably well tolerated, but overall survival was not significantly longer for patients with metastatic castration-resistant prostate cancer treated with this combination, compared with patients treated with docetaxel and prednisone alone. FUNDING: OncoGenex Technologies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/secundario , Progresión de la Enfermedad , Docetaxel , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Prednisona/administración & dosificación , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/patología , Tasa de Supervivencia , Taxoides/administración & dosificación , Tionucleótidos/administración & dosificación
17.
Clin Exp Pharmacol Physiol ; 44(11): 1089-1098, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28681408

RESUMEN

The aim of this study was to evaluate cardiovascular autonomic modulation in response to an orthostatic stress in healthy subjects and Parkinson's disease (PD). The study included 47 controls and 56 PD patients divided into groups (vasoconstrictor PD, vasodilator PD, control) according to vasodilation/vasoconstriction response during 70° head up tilt test. Using impedance cardiography (ICG) and electrocardiography (ECG) we measured stroke volume, cardiac output, left ventricular work index, left ventricular ejection time, acceleration index, index of contractility, Heather index, thoracic fluid content, total peripheral resistance, total arterial compliance. We also analyzed heart rate variability (HRV), using spectral analysis and continuous blood pressure (contBP). At rest, the vasodilator PD group showed significantly higher values of total peripheral resistance and lower values of stroke volume and cardiac output, compared to the vasoconstrictor PD and the control groups. A post-tilt drop in ∆ (change rest - tilt) systolic blood pressure, ∆mean blood pressure, ∆total peripheral resistance and ∆Heather index, and a significantly lower increase in ∆diastolic blood pressure was observed in subjects from the vasodilator PD group compared to the vasoconstrictor PD and the control groups. No statistically significant differences were observed for HRV parameters between the vasoconstrictor and vasodilator PD groups, P > .05. Longer duration and higher disease stage of PD correlated with a reduction in post-tilt systolic blood pressure changes in vasodilator group. Positive inotropy of the cardiac muscle represents a significant factor preventing orthostatic hypotension in PD subjects with a concurrent drop in peripheral vascular resistance during orthostatic stress.


Asunto(s)
Sistema Cardiovascular/fisiopatología , Enfermedad de Parkinson/fisiopatología , Resistencia Vascular , Sistema Nervioso Autónomo/fisiopatología , Sistema Cardiovascular/inervación , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estrés Fisiológico
18.
Cryobiology ; 69(2): 249-55, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25108050

RESUMEN

Over recent years, a considerable increase in the popularity of cryostimulation and whole body cryotherapy (WBC) procedures has occurred both among healthy individuals and in various groups of patients, including those with primary untreated hypertension. The aim of this study was to compare the effects of WBC on the functional parameters of cardiovascular system in normotensive and primarily hypertensive individuals. The study included 26 young male volunteers with normal blood pressure range (NormoBP) and 13 with essential arterial hypertension (HyperBP). Each subject was exposed to cryotherapeutic factor (whole-body cryotherapy/cryostimulation, WBC) at a temperature of approximately -115°C to -125°C for a period of 3 min. The cardiovascular and autonomic parameters were measured noninvasively with Task Force® Monitor. Measurements in a supine position and tilt test were performed "before WBC" and "after WBC". Our study revealed that cryogenic temperatures exert strong modulatory effect on the cardiovascular system. Both groups showed adaptive changes of myocardial and vascular parameters in response to rapid cooling of virtually the whole body surface. While the profiles of some of these changes were similar in both the groups, also several considerable intergroup differences were documented. Consequently, the cryostimulation and cryotherapy treatment should be prescribed carefully to individuals who present with cardiovascular failure of any degree.


Asunto(s)
Crioterapia/métodos , Hipertensión/terapia , Adulto , Barorreflejo , Presión Sanguínea , Fenómenos Fisiológicos Cardiovasculares , Sistema Cardiovascular/fisiopatología , Hipertensión Esencial , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Adulto Joven
19.
Aging Clin Exp Res ; 26(5): 505-10, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24691816

RESUMEN

BACKGROUND AND AIMS: This study objectively analyzed postural instability and cognitive function in patients with Parkinson's disease (PD) and a group of healthy elderly and middle-aged individuals. METHODS: The study included ten healthy middle-aged individuals (range 42-57 years), 14 healthy elderly individuals (range 60-90 years) and 15 PD patients (range 58-93 years). Center of pressure (COP) parameters were determined by means of computed static posturography during free standing with open and closed eyes. The level of cognitive functioning was examined with mini mental state examination (MMSE) and counting backwards test (CBT). RESULTS: Parkinson's disease patients showed significantly lower MMSE scores compared to healthy middle-aged (p = 0.004) and elderly individuals (p = 0.03). Mean duration of CBT in PD patients was significantly longer than in healthy subjects. COP parameters correlated with age of subjects and cognitive function (MMSE score). No significant differences in any stabilographic parameters were observed between healthy elderly subjects and PD patients. CONCLUSIONS: Age is the most significant factor impacting upon the static balance of older individuals during free standing. Compared to middle-aged and elderly individuals without central nervous system impairment, patients with PD present with significant delay in cognitive processes associated with executive function.


Asunto(s)
Factores de Edad , Trastornos del Conocimiento/fisiopatología , Cognición , Enfermedad de Parkinson/fisiopatología , Equilibrio Postural , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas
20.
J Therm Biol ; 45: 75-80, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25436954

RESUMEN

The cardiovascular, autonomic and thermal response to whole-body cryostimulation exposure are not completely known. Thus the aim of this study was to evaluate objectively and noninvasively autonomic and thermal reactions observed after short exposure to very low temperatures. We examined 25 healthy men with mean age 30.1 ± 3.7 years and comparable anthropomorphical characteristic. Each subject was exposed to cryotherapeutic temperatures in a cryogenic chamber for 3 min (approx. -120 °C). The cardiovascular and autonomic parameters were measured noninvasively with Task Force Monitor. The changes in core body temperature were determined with the Vital Sense telemetric measurement system. Results show that 3 min to cryotherapeutic temperatures causes significant changes in autonomic balance which are induced by peripheral and central blood volume changes. Cryostimulation also induced changes in core body temperature, maximum drop of core temperature was observed 50-60 min after the stimulation. Autonomic and thermal reactions to cryostimulation were observed up to 6 h after the exposure and were not harmful for examined subjects.


Asunto(s)
Circulación Sanguínea , Temperatura Corporal , Crioterapia/métodos , Sistema Nervioso Parasimpático/fisiología , Adulto , Volumen Sanguíneo , Crioterapia/efectos adversos , Humanos , Masculino
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