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1.
Pulmonology ; 29(6): 469-477, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36180352

RESUMO

BACKGROUND: Patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) may experience severe acute respiratory failure, even requiring ventilatory assistance. Physiological data on lung mechanics during these events are lacking. METHODS: Patients with AE-IPF admitted to Respiratory Intensive Care Unit to receive non-invasive ventilation (NIV) were retrospectively analyzed. Esophageal pressure swing (ΔPes) and respiratory mechanics before and after 2 hours of NIV were collected as primary outcome. The correlation between positive end-expiratory pressure (PEEP) levels and changes of in dynamic compliance (dynCRS) and PaO2/FiO2 ratio was assessed. Further, an exploratory comparison with a historical cohort of ARDS patients matched 1:1 by age, sequential organ failure assessment score, body mass index and PaO2/FiO2 level was performed. RESULTS: At baseline, AE-IPF patients presented a high respiratory drive activation with ΔPes = 27 (21-34) cmH2O, respiratory rate (RR) = 34 (30-39) bpm and minute ventilation (VE) = 21 (20-26) L/min. Two hours after NIV application, ΔPes, RR and VE values showed a significant reduction (16 [14-24] cmH2O, p<0.0001, 27 [25-30] bpm, p=0.001, and 18 [17-20] L/min, p=0.003, respectively) while no significant change was found in dynamic transpulmonary pressure, expiratory tidal volume (Vte), dynCRS and dynamic mechanical power. PEEP levels negatively correlated with PaO2/FiO2 ratio and dynCRS (r=-0.67, p=0.03 and r=-0.27, p=0.4, respectively). When compared to AE-IPF, ARDS patients presented lower baseline ΔPes, RR, VE and dynamic mechanical power. Differently from AE-IPF, in ARDS both Vte and dynCRS increased significantly following NIV (p=0.01 and p=0.004 respectively) with PEEP levels directly associated with PaO2/FiO2 ratio and dynCRS (r=0.24, p=0.5 and r=0.65, p=0.04, respectively). CONCLUSIONS: In this study, patients with AE-IPF showed a high inspiratory effort, whose intensity was reduced by NIV application without a significant improvement in respiratory mechanics. In an exploratory analysis, AE-IPF patients showed a different mechanical behavior under spontaneous unassisted and assisted breathing compared with ARDS patients of similar severity.


Assuntos
Fibrose Pulmonar Idiopática , Síndrome do Desconforto Respiratório , Humanos , Estudos Retrospectivos , Respiração Artificial , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/terapia , Mecânica Respiratória/fisiologia , Síndrome do Desconforto Respiratório/terapia
3.
Neuropharmacology ; 123: 22-33, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28526609

RESUMO

INTRODUCTION: The mainstay therapy for Parkinson's disease (PD) relies on L-3,4-dihydroxyphenylalanine (L-DOPA) plus a DOPA-decarboxylase inhibitor. However, their effects on colonic dysmotility and inflammation observed in PD are undetermined. This study examined the effects of L-DOPA plus benserazide (BE) on colonic motility and inflammation in rats with central nigrostriatal dopaminergic denervation. METHODS: Neurodegeneration was induced by 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). 6-OHDA animals were treated orally with L-DOPA/BE for 28 days, starting 28 days after 6-OHDA injection. At the end of treatment, in vivo colonic transit was evaluated by a radiologic assay. Electrically stimulated (ES) cholinergic contractions were recorded in vitro from colonic preparations, while acetylcholine release was measured in the incubation medium. Choline acetyltransferase (ChAT) and glial fibrillary acidic protein (GFAP) expression as well as eosinophil and mast cell density were examined in the colonic wall by immunohistochemistry. Colonic TNF and IL-1ß levels were also assayed. RESULTS: 6-OHDA animals displayed: 1) decrease in in vivo colonic transit; 2) impairment of ES-stimulated cholinergic contractions; 3) decreased acetylcholine release from myenteric nerves; 4) decrease in ChAT and increase in GFAP myenteric immunopositivity; 5) increase in eosinophil and mast cell density; 6) increase in TNF and IL-1ß levels. Treatment with L-DOPA/BE elicited an improvement of in vivo and in vitro colonic motor activity, a normalization of acetylcholine release, ChAT immunopositivity, as well as pro-inflammatory cytokine patterns, ganglionic GFAP levels, eosinophil and mast cell density. CONCLUSION: Under dopaminergic nigrostriatal denervation, treatment with L-DOPA/BE ameliorated colonic motility through a normalization of myenteric cholinergic neurotransmission, along with an improvement of colonic inflammation.


Assuntos
Antiparkinsonianos/farmacologia , Benserazida/farmacologia , Colo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Levodopa/farmacologia , Transtornos Parkinsonianos/tratamento farmacológico , Acetilcolina/metabolismo , Administração Oral , Animais , Colina O-Acetiltransferase/metabolismo , Colo/patologia , Colo/fisiopatologia , Trânsito Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/fisiologia , Inflamação/patologia , Inflamação/fisiopatologia , Interleucina-1beta/metabolismo , Masculino , Músculo Liso/efeitos dos fármacos , Músculo Liso/patologia , Músculo Liso/fisiopatologia , Oxidopamina , Transtornos Parkinsonianos/patologia , Transtornos Parkinsonianos/fisiopatologia , Ratos Sprague-Dawley , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Técnicas de Cultura de Tecidos , Fator de Necrose Tumoral alfa/metabolismo
4.
Respir Med ; 109(7): 904-13, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25962649

RESUMO

BACKGROUND: In this retrospective Italian study, which involved all major national interstitial lung diseases centers, we evaluated the effect of pirfenidone on disease progression in patients with IPF. METHODS: We retrospectively studied 128 patients diagnosed with mild, moderate or severe IPF, and the decline in lung function monitored during the one-year treatment with pirfenidone was compared with the decline measured during the one-year pre-treatment period. RESULTS: At baseline (first pirfenidone prescription), the mean percentage forced vital capacity (FVC) was 75% (35-143%) of predicted, and the mean percentage diffuse lung capacity (DLCO) was 47% (17-120%) of predicted. Forty-eight patients (37.5%) had mild disease (GAP index stage I), 64 patients (50%) had moderate IPF (stage II), and 8 patients (6.3%) had severe disease (stage III). In the whole population, pirfenidone attenuated the decline in FVC (p = 0.065), but did not influence the decline in DLCO (p = 0.355) in comparison to the pre-treatment period. Stratification of patients into mild and severe disease groups based on %FVC level at baseline (>75% and ≤75%) revealed that attenuation of decline in FVC (p = 0.002) was more pronounced in second group of patients. Stratification of patients according to GAP index at baseline (stage I vs. II/III) also revealed that attenuation of decline in lung function was more pronounced in patients with more severe disease. CONCLUSIONS: In this national experience, pirfenidone reduced the rate of annual FVC decline (p = 0.065). Since pirfenidone provided significant treatment benefit for patients with moderate-severe disease, our results suggest that the drug may also be effective in patients with more advanced disease.


Assuntos
Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/administração & dosagem , Capacidade Vital/efeitos dos fármacos , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/fisiopatologia , Incidência , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Resultado do Tratamento
5.
Sarcoidosis Vasc Diffuse Lung Dis ; 30 Suppl 1: 52-62, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-24081247

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressively fibrotic interstitial lung disease that is associated with a median survival of 2-5 years from initial diagnosis. To date, the search for an effective treatment has involved numerous clinical trials of investigational agents but without significant success. Nevertheless, research over the past 10 years has provided us with a wealth of information on its histopathology, diagnostic work-up, and a greater understanding of its pathophysiology. Specifically, IPF is no longer thought to be a predominantly pro-inflammatory disorder. Rather, the fibrosis in IPF is increasingly understood to be the result of a fibroproliferative and aberrant wound healing cascade. The development of therapeutic targets has therefore shifted in accordance with this paradigm change. Emerging clinical data from recently published and ongoing trials investigating new potential pharmacological agents should be considered in the routine clinical management of these patients. Based upon encouraging results from randomised-controlled trials showing a positive effect in slowing decline in pulmonary function and reducing disease progression, pirfenidone was approved in 2011 as the first treatment in patients with IPF. This case study describes the clinical course of a patient enrolled into the Phase III and open-label extension studies of pirfenidone.


Assuntos
Anti-Inflamatórios não Esteroides , Fibrose Pulmonar Idiopática , Seguimentos , Humanos , Pulmão , Resultado do Tratamento
6.
Int J Nanomedicine ; 7: 435-47, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22334776

RESUMO

BACKGROUND: We have previously shown that human mesenchymal stem cells (hMSCs) can reduce toxin-induced neurodegeneration in a well characterized rodent model of Parkinson's disease. However, the precise mechanisms, optimal cell concentration required for neuroprotection, and detailed cell tracking need to be defined. We exploited a near-infrared imaging platform to perform noninvasive tracing following transplantation of tagged hMSCs in live parkinsonian rats. METHODS: hMSCs were labeled both with a membrane intercalating dye, emitting in the near- infrared 815 nm spectrum, and the nuclear counterstain, Hoechst 33258. Effects of near-infrared dye on cell metabolism and proliferation were extensively evaluated in vitro. Tagged hMSCs were then administered to parkinsonian rats bearing a 6-hydroxydopamine-induced lesion of the nigrostriatal pathway, via two alternative routes, ie, intrastriatal or intranasal, and the cells were tracked in vivo and ex vivo using near-infrared technology. RESULTS: In vitro, NIR815 staining was stable in long-term hMSC cultures and did not interfere with cell metabolism or proliferation. A significant near-infrared signal was detectable in vivo, confined around the injection site for up to 14 days after intrastriatal transplantation. Conversely, following intranasal delivery, a strong near-infrared signal was immediately visible, but rapidly faded and was completely lost within 1 hour. After sacrifice, imaging data were confirmed by presence/absence of the Hoechst signal ex vivo in coronal brain sections. Semiquantitative analysis and precise localization of transplanted hMSCs were further performed ex vivo using near-infrared imaging. CONCLUSION: Near-infrared technology allowed longitudinal detection of fluorescent-tagged cells in living animals giving immediate information on how different delivery routes affect cell distribution in the brain. Near-infrared imaging represents a valuable tool to evaluate multiple outcomes of transplanted cells, including their survival, localization, and migration over time within the host brain. This procedure considerably reduces the number of animal experiments needed, as well as interindividual variability, and may favor the development of efficient therapeutic strategies promptly applicable to patients.


Assuntos
Rastreamento de Células/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/citologia , Doença de Parkinson/cirurgia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Administração Intranasal , Análise de Variância , Animais , Bisbenzimidazol , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Humanos , Masculino , Células-Tronco Mesenquimais/química , Imagem Molecular , Ratos , Ratos Sprague-Dawley , Córtex Visual/cirurgia
7.
G Ital Med Lav Ergon ; 33(2 Suppl): 57-60, 2011.
Artigo em Italiano | MEDLINE | ID: mdl-22187927

RESUMO

From the 2002 through 2009 years 419 health care workers of the Hospital of Lecco, occupationally exposed to X-ray, were invited to undergo a cancer screening programme for the early diagnosis of cervical, breast, colorectal and prostate cancers. A total of 341 subjects performed the screening tests with an overall compliance of 83,8%; the participation rate to each test was significantly higher than that of general population. Breast cancer was diagnosed and treated in 5 women, cervical premalignant lesions in 8 women and colorectal adenomas in 13 subjects; no prostate cancer was detected. The participation rate, the premalignant and malignant findings and the cost-effectiveness analysis are consistent with the possibility that cancer screening programme can be set out as health promotion activity in health care workers.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Pessoal de Saúde/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/prevenção & controle , Colonoscopia/economia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/prevenção & controle , Análise Custo-Benefício , Detecção Precoce de Câncer/economia , Detecção Precoce de Câncer/métodos , Feminino , Promoção da Saúde , Humanos , Itália/epidemiologia , Masculino , Mamografia/economia , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Serviço Hospitalar de Radiologia , Estudos Retrospectivos , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle
8.
Med Lav ; 98(5): 415-21, 2007.
Artigo em Italiano | MEDLINE | ID: mdl-17907534

RESUMO

BACKGROUND: In many sports (such as rock-climbing and caving) and working activities (e.g., construction and maintenance of buildings, pruning of lung-trunked trees, abseiling in wells) people run the risk of falling from a height. To prevent the effects of any potential fall, personalprotection devices consisting of at least a body holding device (i.e. a harness of some type), a lanyard and a reliable anchor are used. OBJECTIVES: Reporting on the occurrence of vascular thrombosis in subjects undergoing prolonged hanging in a harness, either for work or recreation. METHODS: We investigated patients treated for vascular thrombosis in our hospital in the last 5 years to identify subjects with frequent use of a harness. RESULTS: We identified a 36-year-old rock-climber who developed pulmonary thrombo-embolism and infarction 5 days after he had been wearing a harness for 12 hours consecutively, and a 32 year-old worker who often used a harness to fix wire-nettings to prevent rocks falling from steep places and suffered thrombosis of the left superficial femoral artery. A feature of both cases was the considerable length of time spent hanging in the harness and the absence of alternative risk factors for thrombosis. CONCLUSIONS: Prolonged hanging in a harness can be dangerous in itself because it can produce vascular thrombosis. Reduction of intravascular blood flow (stasis) and compression of the femoral veins by harness groin straps were the likely pathogenetic mechanisms of the described diseases. The importance is stressed of prevention, which must be based on planned regular breaks in the hanging position, checking on the fit and comfort level of the harness before it is first used, as well as medical surveillance of the subjects who spend prolonged periods in a harness for work or recreation.


Assuntos
Artéria Femoral , Montanhismo/lesões , Doenças Profissionais/etiologia , Embolia Pulmonar/etiologia , Trombose/etiologia , Administração Oral , Adulto , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Biópsia , Implante de Prótese Vascular , Artéria Femoral/patologia , Artéria Femoral/cirurgia , Seguimentos , Heparina/administração & dosagem , Heparina/uso terapêutico , Humanos , Masculino , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/tratamento farmacológico , Radiografia Torácica , Trombose/patologia , Trombose/cirurgia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
9.
Int Arch Occup Environ Health ; 80(4): 298-305, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16957957

RESUMO

OBJECTIVES: Aims of this study were to define (1) whether toluene diisocyanate (TDI) bronchial hyper-responsiveness persists in subjects with occupational asthma after long-term cessation of exposure; (2) whether evolution of specific bronchial TDI sensitization and symptoms and functional abnormalities of asthma were coincident, and (3) the determinants at the time of diagnosis of patients' outcome. METHODS: Twenty-five nonatopic spray painters with occupational asthma due to TDI were re-examined 58 +/- 7 (46-73) months after removal from exposure. On both examinations, the severity of asthmatic symptoms and the need for antiasthma treatment over the past 12 months were graded and lung function tests, measurement of airway responsiveness to methacholine (PD(20)), circulating total IgE and TDI-HSA specific IgE, skin tests with common inhalant allergens and specific bronchial challenge with TDI were carried out. RESULTS: Seven subjects were still TDI-reactors and 18 lost reactivity to it. All persistent reactors had still asthma and their symptom score, medication score, FEV(1), PD(20) and serum IgE were unchanged between assessments. In the 18 subjects no longer responsive to TDI, 8 had still features of asthma: their symptom and medication score had improved significantly, but FEV(1), PD(20) and serum IgE had not significantly changed; the other ten patients no longer reactors to TDI were also asymptomatic and their PD(20) had become normal. The duration of symptomatic exposure to TDI was the only feature at diagnosis that differentiated patients with persistent TDI airway hyper-responsiveness and asthma from those who were no longer responsive to TDI but still asthmatic and those who were no longer responsive to TDI and no longer asthmatic (4 +/- 1.6; 2.1 +/- 0.8; 0.6 +/- 0.3 years, respectively; p < 0.001). CONCLUSION: our study demonstrates that airway sensitization to TDI and symptoms and functional airway abnormalities of asthma can persist for years after cessation of exposure and may have different outcome. If avoidance of the offending agent takes place within few months after the development of symptoms, remission of asthma and of TDI bronchial hyper-responsiveness can occur, whereas waiting for years makes it too late to cure asthma and, in the end, to reverse specific sensitization.


Assuntos
Asma/induzido quimicamente , Doenças Profissionais/imunologia , Exposição Ocupacional/efeitos adversos , Tolueno 2,4-Di-Isocianato/efeitos adversos , Adulto , Asma/fisiopatologia , Asma/prevenção & controle , Testes de Provocação Brônquica , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Recuperação de Função Fisiológica
11.
J Pediatr Endocrinol Metab ; 13 Suppl 1: 821-6, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10969927

RESUMO

The availability of recombinant human growth hormone (GH) and the optimization of substitutive therapy have improved final growth in children with GH deficiency, but despite this some of them fail to grow to their genetic potential. In particular, this may occur in patients who started the substitutive therapy too late and/or in whom bone age progressed too fast during GH administration. In these patients, with unfavorable auxological characteristics, the administration of a GnRH agonist in combination with GH may slow down bone maturation and prolong prepubertal growth, mimicking, to some extent, the growth pattern of patients with GH + Gn deficiency who grow better than children with isolated GHD. A different condition in which such a combined therapy might be used is the short normal child. As they are short but normally-growing children, the onset of puberty is in general appropriate for their chronological age but precocious for their height age. Thus, slowing down pubertal maturation may increase the time available for growth. GH would sustain growth during both GnRHa administration and after its withdrawal, when puberty starts again. Our preliminary results suggest that the administration of GH + GnRHa in combination may have a positive effect on final height in selected children with isolated GHD and in short normal children.


Assuntos
Estatura/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/agonistas , Hormônio do Crescimento/uso terapêutico , Criança , Quimioterapia Combinada , Hormônio do Crescimento/deficiência , Humanos , Valores de Referência
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