Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
1.
Respir Care ; 68(1): 60-66, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36167848

RESUMO

BACKGROUND: A proportion of patients with COVID-19 need hospitalization due to severe respiratory symptoms. We sought to analyze characteristics of survivors of severe COVID-19 subsequently admitted to in-patient pulmonary rehabilitation and identify their rehabilitation needs. METHODS: From the COVID-19 Registry of Fondazione Don Gnocchi, we extracted 203 subjects admitted for in-patient pulmonary rehabilitation after severe COVID-19 from April 2020-September 2021. Specific information on acute-hospital stay and clinical and functional characteristics on admission to rehabilitation units were collected. RESULTS: During the acute phase of disease, 168 subjects received mechanical ventilation for 26 d; 85 experienced delirium during their stay in ICU. On admission to rehabilitation units, 20 subjects were still on mechanical ventilation; 57 had tracheostomy; 142 were on oxygen therapy; 49 were diagnosed critical illness neuropathy; 162 showed modified Barthel Index < 75; only 51 were able to perform a 6-min walk test; 32 of 90 scored abnormal at Montreal Cognitive Assessment; 43 of 88 scored abnormal at Hospital Anxiety and Depression Scale; 65 scored ≥ 2 at Malnutrition Universal Screening Tool, and 95 showed dysphagia needing logopedic treatment. CONCLUSIONS: Our analysis shows that subjects admitted for in-patient pulmonary rehabilitation after severe COVID-19 represent an extraordinarily multifaceted and clinically complex patient population who need customized, comprehensive rehabilitation programs carried out by teams with different professional skills. The need for step-down facilities, such as sub-intensive rehabilitation units, is also highlighted.


Assuntos
COVID-19 , Humanos , Unidades de Terapia Intensiva , Respiração Artificial , Hospitalização , Tempo de Internação
3.
Acta Biomed ; 91(3): e2020087, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921783

RESUMO

Hashimoto encephalopathy (HE) is a rare but controversial entity encompassing a variety of neuropsychological presentations in the setting of autoimmune thyroid disease. HE, mostly described in adults, with a female­to­male ratio of 4:1, is a relatively rare entity in the pediatric population and probably under recognized as a cause of acute encephalopathy in children and adolescents. A number of pathogenetic mechanisms have been suggested. Female prevalence, presence of autoantibodies, fluctuating course, and response to immunomodulatory therapy suggest the autoimmune nature of the disease. Existing diagnostic criteria for adults require modification to be applied to children and adolescents, who differ from adults in their clinical presentations, clinical findings, autoantibody profiles, treatment response, and long-term outcomes. A combination of neurological findings, positive antithyroid autoantibodies, and responsiveness to steroids is diagnostic of HE. We add a new case of HE in an adolescent girl and review the current HE literature.


Assuntos
Encefalopatias , Encefalite , Doença de Hashimoto , Adolescente , Autoanticorpos , Encefalopatias/etiologia , Encefalite/diagnóstico , Feminino , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/tratamento farmacológico , Humanos
4.
Monaldi Arch Chest Dis ; 90(2)2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32573175

RESUMO

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.


Assuntos
Infecções por Coronavirus/reabilitação , Modalidades de Fisioterapia , Pneumonia Viral/reabilitação , Insuficiência Respiratória/reabilitação , Terapia Respiratória/métodos , Assistência Ambulatorial , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Técnica Delphi , Teste de Esforço , Humanos , Unidades de Terapia Intensiva , Itália , Estado Nutricional , Pandemias , Equipamento de Proteção Individual , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , Qualidade de Vida , Testes de Função Respiratória , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , SARS-CoV-2 , Transtornos de Estresse Pós-Traumáticos
5.
Respiration ; 99(6): 493-499, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428909

RESUMO

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning for COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which are described in this paper to face the emergency.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Modalidades de Fisioterapia , Pneumonia Viral/complicações , Insuficiência Respiratória/reabilitação , COVID-19 , Infecções por Coronavirus/epidemiologia , Humanos , Itália , Pandemias , Gravidade do Paciente , Pneumonia Viral/epidemiologia , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/reabilitação , Insuficiência Respiratória/etiologia , SARS-CoV-2
6.
Phys Ther ; 100(8): 1249-1259, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32329780

RESUMO

OBJECTIVE: The study aimed to evaluate whether high-flow oxygen therapy (HFOT) during training was more effective than oxygen in improving exercise capacity in hypoxemic chronic obstructive pulmonary disease (COPD). METHODS: A total of 171 patients with COPD and chronic hypoxemia were consecutively recruited in 8 rehabilitation hospitals in a randomized controlled trial. Cycle-ergometer exercise training was used in 20 supervised sessions at iso inspiratory oxygen fraction in both groups. Pre- and post-training endurance time (Tlim), 6-minute walking distance (6MWD), respiratory and limb muscle strength, arterial blood gases, Barthel Index, Barthel Dyspnea Index, COPD Assessment Test, Maugeri Respiratory Failure questionnaire, and patient satisfaction were evaluated. RESULTS: Due to 15.4% and 24.1% dropout rates, 71 and 66 patients were analyzed in HFOT and Venturi mask (V-mask) groups, respectively. Exercise capacity significantly improved after training in both groups with similar patient satisfaction. Between-group difference in post-training improvement in 6MWD (mean: 17.14 m; 95% CI = 0.87 to 33.43 m) but not in Tlim (mean: 141.85 seconds; 95% CI = -18.72 to 302.42 seconds) was significantly higher in HFOT. The minimal clinically important difference of Tlim was reached by 47% of patients in the V-mask group and 56% of patients in the HFOT group, whereas the minimal clinically important difference of 6MWD was reached by 51% of patients in the V-mask group and 69% of patients in the HFOT group, respectively. CONCLUSION: In patients with hypoxemic COPD, exercise training is effective in improving exercise capacity. IMPACT STATEMENT: The addition of HFOT during exercise training is not more effective than oxygen through V-mask in improving endurance time, the primary outcome, whereas it is more effective in improving walking distance.


Assuntos
Dispneia/terapia , Tolerância ao Exercício/fisiologia , Exercício Físico , Oxigenoterapia/métodos , Doença Pulmonar Obstrutiva Crônica/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Gasometria , Doença Crônica , Intervalos de Confiança , Dispneia/sangue , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Força Muscular , Ventilação não Invasiva , Oxigênio/administração & dosagem , Satisfação do Paciente , Doença Pulmonar Obstrutiva Crônica/sangue , Método Simples-Cego , Teste de Caminhada
7.
Eur J Phys Rehabil Med ; 56(6): 713-724, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33494558

RESUMO

BACKGROUND: To standardize assessment and coordinate processes in stroke rehabilitation, an integrated care pathway (ICP) was developed in an Italian Rehabilitation and Research Institution by a knowledge-translation interdisciplinary process, from evidence-based guidelines to rehabilitation practice. The ICP was implemented in two pilot Tuscan rehabilitation Centers. AIM: The purpose of this study was to describe ICP development and assess the ICP effects on postacute stroke inpatient rehabilitation outcomes. DESIGN: Prospective observational study, before and after comparison. SETTING: Two Tuscan inpatient rehabilitation centers. POPULATION: Patients accessing either centers for intensive rehabilitation after acute stroke. METHODS: Two cohorts were prospectively recruited before (2015-2017) and after (2018) implementation of the pathway. The primary outcome was change in activities of daily living disability, assessed by the modified Barthel Index (mBI) from admission to discharge. Secondary outcomes included length of stay (LOS), adverse outcomes, and changes in communication ability, trunk control, pain, ambulation, bladder catheter (Y/N), bedsores (Y/N). RESULTS: In 2015-2017, 443 postacute stroke patients (mean age 77±11 years, 47% women), while in 2018, 84 patients (mean age 76±13 years, 61% women) were admitted to the two facilities. Comparing the 2018 vs. the 2015-17 cohort, the mean mBI increase was not substantially different (26 vs. 24 points), nor were LOS (37±18 vs. 36±16 days), adverse outcomes, discharge destination, and improvement of ambulation, pain, and communication (P>0.05). Instead, a significantly higher improvement of trunk control (trunk control test: 69.6±33.2 vs. 79.0±31.3, P=0.019), and a higher percentage of bedsore resolution (13% vs. 5%, P=0.033), and bladder catheter removal (37% vs. 17% P<0.001) were observed in 2018 vs. 2015-2017. CONCLUSIONS: Compared to prior practice, ICP was associated to improvement of trunk control recovery, bladder catheter removal, and bedsores resolution. Further ICP implementation on a larger scale is needed to verify improvements of stroke inpatient rehabilitation outcomes. CLINICAL REHABILITATION IMPACT: An evidence-based stroke rehabilitation ICP was interdisciplinary developed and implemented in two rehabilitation centers of a multicenter Italian health group. ICP implementation as to inpatient intensive postacute stroke rehabilitation was associated to improved trunk control recovery, bladder catheter removal, and bedsore resolution. Further ICP implementation will allow multicenter studies and quality benchmarking.


Assuntos
Prestação Integrada de Cuidados de Saúde , Desenvolvimento de Programas , Melhoria de Qualidade , Reabilitação do Acidente Vascular Cerebral/métodos , Reabilitação do Acidente Vascular Cerebral/normas , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Avaliação da Deficiência , Medicina Baseada em Evidências , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica , Centros de Reabilitação
8.
Sleep Med ; 64: 106-111, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31678699

RESUMO

OBJECTIVES: This study evaluated heart failure (HF) patients who underwent cardiac resynchronization therapy (CRT) and who had device-documented sleep-disordered breathing (SDB). We found gender differences in acute changes in SDB due to CRT impact. BACKGROUND: SDB typically occurs in HF patients. However, the role of SDB and its response to CRT in HF patients, as well as the relation with gender are currently not fully researched. METHODS: Among 63 consecutive patients who received CRT with an SDB algorithm, 23 patients documented SDB at one-month cardiac device interrogation and represented our population. We defined a Sleep apnoea Severity SCore(SSSC), and consequently, patients were categorized to have mild, moderate, and severe sleep apnoea syndrome divided into two groups: Group-1: 18 males (78%); Group-2: 5 females (22%). We evaluated the variation of apnoea burden and CRT response based on gender differences. RESULTS: A significantly higher proportion of patients in the male group were non-responders to CRT at 12-months follow-up (p = 0.076) while in the female population 5/5 patients (100%) were responders to CRT at the same follow-up time (p = 0.021). Among Group-2 subjects, we documented a significant linear decrease in SSSC(p > 0,01) while in Group-1 the CRT effect on SSSC was variable. At 12-months follow-up, the difference in SSSC between the two groups was statistically significant (p < 0.001). CONCLUSIONS: Our study reports a correlation between CRT response and sleep apnoea burden considering gender differences. In particular, HF-women responders to CRT demonstrate a significant linear decrease in sleep apnoea burden determined through a device algorithm, when compared to a similar male population. Further research is needed to confirm these findings.


Assuntos
Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca/complicações , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/terapia , Idoso de 80 Anos ou mais , Algoritmos , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Estudos Retrospectivos , Fatores Sexuais , Síndromes da Apneia do Sono/epidemiologia , Resultado do Tratamento
9.
Respirology ; 23(2): 182-189, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28940820

RESUMO

BACKGROUND AND OBJECTIVE: The role of non-invasive ventilation (NIV) during exercise training (ET) in patients with chronic respiratory failure (CRF) is still unclear. The aim of this study was to test whether NIV during ET had an additional effect in increasing the 6-min walking distance (6MWD) and cycle endurance time compared with ET alone. METHODS: All patients underwent 20 sessions of cycle training over 3 weeks and were randomly assigned to ET with NIV or ET alone. Outcome measures were 6MWD (primary outcome), incremental and endurance cycle ergometer exercise time, respiratory muscle function, quality of life by the Maugeri Respiratory Failure questionnaire (MRF-28), dyspnoea (Medical Research Council scale) and leg fatigue at rest. RESULTS: Forty-two patients completed the study. Following training, no significant difference in 6MWD changes were found between groups. Improvement in endurance time was significantly greater in the NIV group compared with the non-NIV training group (754 ± 973 vs 51 ± 406 s, P = 0.0271); dyspnoea improved in both groups, while respiratory muscle function and leg fatigue improved only in the NIV ET group. MRF-28 improved only in the group training without NIV. CONCLUSION: In CRF patients on long-term NIV and long-term oxygen therapy (LTOT), the addition of NIV to ET sessions resulted in an improvement in endurance time, but not in 6MWD.


Assuntos
Terapia por Exercício , Tolerância ao Exercício/fisiologia , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica/reabilitação , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/reabilitação , Adulto , Idoso , Idoso de 80 Anos ou mais , Dispneia/etiologia , Dispneia/fisiopatologia , Dispneia/prevenção & controle , Feminino , Humanos , Hipercapnia/etiologia , Hipercapnia/fisiopatologia , Hipercapnia/terapia , Hipóxia/etiologia , Hipóxia/fisiopatologia , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxigenoterapia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Qualidade de Vida , Insuficiência Respiratória/complicações , Músculos Respiratórios/fisiopatologia
10.
BMC Pulm Med ; 17(1): 130, 2017 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29017478

RESUMO

BACKGROUND: Recent evidences show that Pulmonary Rehabilitation (PR) is effective in patients with Interstitial Lung Disease (ILD). It is still unclear whether disease severity and/or etiology might impact on the reported benefits. We designed this prospective study 1) to confirm the efficacy of rehabilitation in a population of patients with ILDs and 2) to investigate whether baseline exercise capacity, disease severity or ILD etiology might affect outcomes. METHODS: Forty-one patients (IPF 63%, age 66.9 ± 11 ys) were enrolled in a standard PR course in two centers. Lung function, incremental and endurance cyclo-ergometry, Six Minutes Walking Distance (6MWD), chronic dyspnea (Medical Research Council scale-MRC) and quality of life (St. George Respiratory Questionnaire-SGRQ) were recorded before and at the end of PR to measure any pre-to-post change. Correlation coefficients between the baseline level of Diffuse Lung Capacity for Carbon monoxide (DLCO), Forced Vital Capacity (FVC), 6MWD, power developed during incremental endurance test, GAP index (in IPF patients only) and etiology (IPF or non-IPF) with the functional improvement at the 6MWDT (meters), at the incremental and endurance cyclo-ergometry (endurance time) and the HRQoL were assessed. RESULTS: Out of the 41 patients, 97% (n = 40) completed the PR course. Exercise performance (both at peak load and submaximal effort), symptoms (iso-time dyspnea and leg fatigue), SGRQ and MRC significantly improved after PR (p < .001). Patients with lower baseline 6MWD showed greater improvement in 6MWD (Spearman r score = - .359, p = .034) and symptoms relief at SGRQ (r = -.315, p = .025) regardless of underlying disease. CONCLUSION: Present study confirms that comprehensive rehabilitation is feasible and effective in patients with ILD of different severity and etiology. The baseline submaximal exercise capacity inversely correlates with both functional and symptom gains in this heterogeneous population.


Assuntos
Tolerância ao Exercício , Exercício Físico , Doenças Pulmonares Intersticiais/fisiopatologia , Doenças Pulmonares Intersticiais/reabilitação , Idoso , Dispneia/etiologia , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários , Capacidade Vital , Teste de Caminhada
11.
Clin Case Rep ; 5(9): 1465-1467, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28878905

RESUMO

Sleep apnea syndrome (SAS) is a chronic condition associated with cardiovascular disease. In some pacemakers, an advanced algorithm using transthoracic impedance may be used to identify SAS. This algorithm may be also a useful tool for a long-term monitoring helping physicians to optimize therapy, reducing risk factors, and improving therapeutic compliance.

12.
Oncotarget ; 6(35): 37511-25, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26462020

RESUMO

The SGK1 kinase is pivotal in signal transduction pathways operating in cell transformation and tumor progression. Here, we characterize in depth a novel potent and selective pyrazolo[3,4-d]pyrimidine-based SGK1 inhibitor. This compound, named SI113, active in vitro in the sub-micromolar range, inhibits SGK1-dependent signaling in cell lines in a dose- and time-dependent manner. We recently showed that SI113 slows down tumor growth and induces cell death in colon carcinoma cells, when used in monotherapy or in combination with paclitaxel. We now demonstrate for the first time that SI113 inhibits tumour growth in hepatocarcinoma models in vitro and in vivo. SI113-dependent tumor inhibition is dose- and time-dependent. In vitro and in vivo SI113-dependent SGK1 inhibition determined a dramatic increase in apoptosis/necrosis, inhibited cell proliferation and altered the cell cycle profile of treated cells. Proteome-wide biochemical studies confirmed that SI113 down-regulates the abundance of proteins downstream of SGK1 with established roles in neoplastic transformation, e.g. MDM2, NDRG1 and RAN network members. Consistent with knock-down and over-expressing cellular models for SGK1, SI113 potentiated and synergized with radiotherapy in tumor killing. No short-term toxicity was observed in treated animals during in vivo SI113 administration. These data show that direct SGK1 inhibition can be effective in hepatic cancer therapy, either alone or in combination with radiotherapy.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Raios gama , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas Imediatamente Precoces/antagonistas & inibidores , Neoplasias Hepáticas/tratamento farmacológico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinas/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Western Blotting , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Proteínas Imediatamente Precoces/metabolismo , Técnicas Imunoenzimáticas , Técnicas In Vitro , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Proteínas Serina-Treonina Quinases/metabolismo , Proteoma/análise , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Cell Physiol Biochem ; 35(5): 2006-18, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25871776

RESUMO

BACKGROUND/AIMS: Published observations on serum and glucocorticoid regulated kinase 1 (Sgk1) knockout murine models and Sgk1-specific RNA silencing in the RKO human colon carcinoma cell line point to this kinase as a central player in colon carcinogenesis and in resistance to taxanes. METHODS: By in vitro kinase activity inhibition assays, cell cycle and viability analysis in human cancer model systems, we describe the biologic effects of a recently identified kinase inhibitor, SI113, characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold, that shows specificity for Sgk1. RESULTS: SI113 was able to inhibit in vitro cell growth in cancer cells derived from tumors with different origins. In RKO cells, this kinase inhibitor blocked insulin-dependent phosphorylation of the Sgk1 substrate Mdm2, the main regulator of p53 protein stability, and induced necrosis and apoptosis when used as a single agent. Finally, SI113 potentiated the effects of paclitaxel on cell viability. CONCLUSION: Since SI113 appears to be effective in inducing cell death in RKO cells, potentiating paclitaxel sensitivity, we believe that this new molecule could be efficiently employed, alone or in combination with paclitaxel, in colon cancer chemotherapy.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas Imediatamente Precoces/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinas/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Proteínas Imediatamente Precoces/metabolismo , Insulina/farmacologia , Células MCF-7 , Necrose , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/metabolismo , Estabilidade Proteica , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Pirazóis/química , Pirazóis/uso terapêutico , Pirimidinas/química , Pirimidinas/uso terapêutico , Proteína Supressora de Tumor p53/metabolismo
14.
J Chem Inf Model ; 54(7): 1828-32, 2014 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-24896223

RESUMO

The serum/glucocorticoid-inducible kinase 1 (Sgk1) has demonstrated antiapoptotic function and the capability to regulate cell survival, proliferation, and differentiation. A pivotal role of Sgk1 in carcinogenesis and in resistance to anticancer therapy has been suggested. With the aim of identifying new Sgk1 modulators, 322 pyrazolo-pyrimidine derivatives have been virtually screened with respect to a crystallographic model of Sgk1. The top five ranked compounds have been evaluated demonstrating Sgk1 inhibition in vitro and selectivity compared to RAC-alpha serine/threonine-protein kinase (Akt1).


Assuntos
Simulação por Computador , Descoberta de Drogas , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinas/química , Linhagem Celular Tumoral , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/metabolismo , Pirazóis/química , Pirazóis/metabolismo
15.
Respir Care ; 59(5): 709-17, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24149672

RESUMO

BACKGROUND: Exercise training improves both exercise tolerance and quality of life in patients with COPD. The intensity of exercise training is crucial to achieve a true physiologic effect. However, in COPD patients, exertional dyspnea and leg fatigue mean that the patient cannot maintain intensity of training for enough time to yield a physiologic training effect. The use of noninvasive ventilation (NIV) support has been proposed as an alternative strategy to improve exercise tolerance and respiratory and cardiovascular performances. The first aim of our meta-analysis was to evaluate exercise training with NIV in terms of physiologic effects after the completion of a pulmonary rehabilitation program. The second aim was to investigate the dose-response relationship between physical improvement and training intensity. METHODS: Literature research was performed using MEDLINE, Embase, and CINAHL. Meta-analysis and meta-regressions were performed using random effects models. RESULTS: Eight studies provided a proper description of a training schedule in stable COPD patients. A similar effect between NIV and placebo was observed for the outcomes considered despite differences between studies. However, subjects experienced a relevant and statistically significant improvement after rehabilitation for almost all of the outcomes considered. Heart rate (6 beats/min [95% CI 0.94-11.01], P = .02), work load (9.73 W [95% CI 3.78-15.67], P < .001), and oxygen consumption (242.11 mL/min [95% CI 154.93-329.9], P < .001) significantly improved after training. Improvements in heart rate and work load were significantly correlated to training intensity. CONCLUSIONS: Given the small number of available studies, the small sample sizes, and the complete absence of power calculation, we think that this topic deserves a more in-depth investigation. Randomized clinical trials with larger sample sizes based on statistical power calculations and designed to investigate the effect of training duration and intensity on rehabilitation are needed to confirm results in this important field.


Assuntos
Tolerância ao Exercício/fisiologia , Ventilação não Invasiva , Condicionamento Físico Humano/fisiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/reabilitação , Frequência Cardíaca , Humanos , Consumo de Oxigênio , Condicionamento Físico Humano/métodos , Esforço Físico/fisiologia
16.
Respir Physiol Neurobiol ; 190: 124-30, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24140573

RESUMO

PURPOSE: The interrelations among chest wall kinematics (displacement and configuration), ventilatory profile and dyspnea relief following cycle exercise training (EXT) have not been systematically evaluated in hyperinflated chronic obstructive pulmonary disease (COPD) patients. We hypothesize that a decrease in ventilation affects dyspnea relief, regardless of the changes in chest wall kinematics. METHODS: Fourteen patients were studied before and after 24-session exercise training program. We evaluated the volumes of chest wall and its compartments (rib cage, and abdomen) using optoelectronic plethysmography. RESULTS: At iso-time EXT (i) reduced ventilation, respiratory frequency and dyspnea (by Borg scale), mildly improved rib cage configuration, but left operational volumes unchanged; (ii) Borg was much smaller for any comparable inspiratory reserve volume (IRVcw), and a decrease in IRVcw was tolerated much better for any given Borg. CONCLUSIONS: Regardless of the changes in chest wall kinematics, a decrease in ventilation attenuates dyspnea following EXT.


Assuntos
Abdome/fisiopatologia , Dispneia/etiologia , Dispneia/reabilitação , Terapia por Exercício/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/reabilitação , Idoso , Tolerância ao Exercício , Humanos , Estudos Longitudinais , Medidas de Volume Pulmonar , Masculino , Movimento (Física) , Pletismografia , Doença Pulmonar Obstrutiva Crônica/patologia , Costelas/fisiopatologia , Espirometria , Parede Torácica/fisiopatologia
17.
J Rehabil Med ; 45(5): 504-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23468060

RESUMO

BACKGROUND: Although the six-minute walk test (6MWT) is widely used in cardiac rehabilitation, little is known about the ventilatory strategies adopted by older patients who have recently undergone median sternotomy, in order to meet the increased metabolic demand in the 6MWT. METHODS: Using a portable gas-analyser we assessed the breathing patterns in the 6MWT before and after a 3-week rehabilitation programme in 84 older patients, 58 men and 26 women, mean age 71 years (standard deviation (SD) 6 years), who had undergone median sternotomy. RESULTS: After rehabilitation, patients increased end-test ventilation (33.1 l (SD 9.8) vs. 30.9 l (SD 8.4), p < 0.001) by increasing tidal volume (1.158 l (SD 0.298) vs. 1.065 l (SD 0.255), p < 0.001), while breathing frequency remained unchanged (29.9 bpm (SD 5.4) vs. 30.2 bpm (SD 5.8), p = 0.621). As a consequence, the ventilatory equivalent for CO2, was significantly improved (39.9 (SD 5.3) vs. 43.5 (SD 7.4), p < 0.001). Furthermore, the improvement in ventilatory efficiency was significantly (p < 0.001) correlated with the improvement in the distance walked on the 6MWT. CONCLUSION: Older patients who have undergone median sternotomy meet the increased metabolic demand on the 6MWT after cardiac rehabilitation by increasing tidal volume. Accordingly, we should consider including as a routine specific exercises for inspiratory muscle training in current rehabilitation programmes to reduce inspiratory muscle effort and further improve ventilatory efficiency.


Assuntos
Procedimentos Cirúrgicos Cardíacos/reabilitação , Teste de Esforço , Cardiopatias/cirurgia , Respiração , Esternotomia/reabilitação , Idoso , Feminino , Cardiopatias/fisiopatologia , Humanos , Masculino , Ventilação Pulmonar , Caminhada/fisiologia
18.
Respir Med ; 107(5): 649-55, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23347530

RESUMO

Anxiety and depression can increase the intensity of dyspnea out of proportion to the impairment in cardiorespiratory function and may contribute to the degree of disability associated with dyspnea. The effect of anxiety/depression on the sensory and affective components of reported dyspnea in patients with respiratory disorders might be of particular importance in improving the accuracy of the diagnostic process. However, the exact cause-relationship between dyspnea and anxiety/depression are unclear. A multidimensional model of dyspnea subsuming sensory components (i.e. intensity and quality) and affective components has recently been proposed. Affective responses drive patients to seek treatment which can cause them to alter their lifestyle to avoid dyspnea. Brain imaging techniques help identify distinct cortical structures involved in processing the discrete components of dyspnea.


Assuntos
Dispneia/psicologia , Emoções , Ansiedade/complicações , Asma/complicações , Asma/psicologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Depressão/complicações , Dispneia/etiologia , Dispneia/fisiopatologia , Humanos
19.
Respir Physiol Neurobiol ; 183(3): 193-200, 2012 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-22772311

RESUMO

We have tested the hypothesis that high mass loading effects and obstructive sleep apnea (OSA) constrain the ventilatory response to exercise in morbidly obese subjects as compared to their counterparts without OSA. Fifteen obese patients with (8) and without OSA and 12 lean healthy subjects performed incremental cycle exercise. The functional evaluation included ventilation, oxygen uptake, carbon dioxide production, end-expiratory-lung-volumes (EELV), inspiratory capacity, heart rate, dyspnea and leg effort (by a modified Borg scale). Changes in ventilation and dyspnea per unit changes in work rate and metabolic variables were similar in the three groups. Breathing pattern and heart rate increased from rest to peak exercise similarly in the three groups. Leg effort was the prevailing symptom for stopping exercise in most subjects. In conclusion, OSA does not limit exercise capacity in morbidly obese subjects. Ventilation contributes to exertional dyspnea similarly as in lean subjects and in obese patients regardless of OSA.


Assuntos
Teste de Esforço/métodos , Exercício Físico/fisiologia , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Ventilação Pulmonar/fisiologia , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Feminino , Humanos , Medidas de Volume Pulmonar/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Med Sci Sports Exerc ; 44(6): 1049-56, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22595983

RESUMO

PURPOSE: Whether dyspnea, chest wall dynamic hyperinflation, and abnormalities of rib cage motion are interrelated phenomena has not been systematically evaluated in patients with chronic obstructive pulmonary disease (COPD). Our hypothesis that they are not interrelated was based on the following observations: (i) externally imposed expiratory flow limitation is associated with no rib cage distortion during strenuous incremental exercise, with indexes of hyperinflation not being correlated with dyspnea, and (ii) end-expiratory chest wall volume may either increase or decrease during exercise in patients with COPD, with those who hyperinflate being as breathless as those who do not. METHODS: Sixteen patients breathed either room air or 50% supplemental O2 at 75% of peak exercise in randomized order. We evaluated the volume of chest wall (V(cw)) and its compartments: the upper rib cage (V(rcp)), lower rib cage (V(rca)), and abdomen (V(ab)) using optoelectronic plethysmography; rib cage distortion was assessed by measuring the phase angle shift between V(rcp) and V(rca). RESULTS: Ten patients increased end-expiratory V(cw) (V(cw,ee)) on air. In seven hyperinflators and three non-hyperinflators, the lower rib cage paradoxed inward during inspiration with a phase angle of 63.4° ± 30.7° compared with a normal phase angle of 16.1° ± 2.3° recorded in patients without rib cage distortion. Dyspnea (by Borg scale) averaged 8.2 and 9 at the end of exercise on air in patients with and without rib cage distortion, respectively. At iso-time during exercise with oxygen, decreased dyspnea was associated with a decrease in ventilation regardless of whether patients distorted the rib cage, dynamically hyperinflated, or deflated the chest wall. CONCLUSIONS: Dyspnea, chest wall dynamic hyperinflation, and rib cage distortion are not interrelated phenomena.


Assuntos
Dispneia/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Costelas/fisiopatologia , Parede Torácica/fisiopatologia , Idoso , Análise de Variância , Teste de Esforço , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Radiografia Torácica , Testes de Função Respiratória , Fumar/efeitos adversos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...