Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a colombian family

Background: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. Objective: we describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. Methods: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot-Marie-Tooth disease, type 4A. Results: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease.

Caractérisation du syndrome de chevauchement de l’asthme et de la maladie pulmonaire obstructive chronique

Maladies fréquentes, l’asthme touche 8,4% de la population canadienne âgée de 12 ans et plus et la maladie pulmonaire obstructive chronique (MPOC) touche de 5 à 15% de la population âgée entre 35 et 79 ans. L’asthme et la MPOC peuvent coexister chez un patient. Ce phénomène appelé syndrome de chevauchement de l’asthme et de la MPOC (ACOS) toucherait environ 10% à 55% des patients MPOC. Afin de mieux caractériser l’ACOS et les effets indésirables des médicaments utilisés pour traiter la MPOC, deux études ont été mises en place. Une première étude réalisée auprès de pneumologues a permis de décrire les méthodes de diagnostic, de traitement et d’évaluation de la maitrise de l’ACOS dans la pratique clinique. Les pneumologues rapportent que le diagnostic devrait être basé sur les caractéristiques cliniques, les tests de fonction pulmonaire et l'intuition clinique du médecin. De plus, un corticostéroïde inhalé en combinaison et un bronchodilatateur inhalé à longue durée d’action devraient être introduits rapidement dans le plan de traitement. La deuxième étude a permis d’évaluer la fréquence des effets indésirables chez les patients MPOC/ACOS traités avec un bronchodilatateur inhalé à longue durée d’action. Cette étude démontre que les effets indésirables sont fréquents chez les patients MPOC/ACOS et que la sécheresse buccale et la gorge sèche sont les plus rapportés. Ces résultats démontrent que la mise en place de lignes directrices pour l’ACOS ainsi qu’une meilleure connaissance du profil de tolérance des bronchodilatateurs inhalés à longue durée d’action seraient bénéfiques pour les patients

Caractérisation du syndrome de chevauchement de l’asthme et de la maladie pulmonaire obstructive chronique

Maladies fréquentes, l’asthme touche 8,4% de la population canadienne âgée de 12 ans et plus et la maladie pulmonaire obstructive chronique (MPOC) touche de 5 à 15% de la population âgée entre 35 et 79 ans. L’asthme et la MPOC peuvent coexister chez un patient. Ce phénomène appelé syndrome de chevauchement de l’asthme et de la MPOC (ACOS) toucherait environ 10% à 55% des patients MPOC. Afin de mieux caractériser l’ACOS et les effets indésirables des médicaments utilisés pour traiter la MPOC, deux études ont été mises en place. Une première étude réalisée auprès de pneumologues a permis de décrire les méthodes de diagnostic, de traitement et d’évaluation de la maitrise de l’ACOS dans la pratique clinique. Les pneumologues rapportent que le diagnostic devrait être basé sur les caractéristiques cliniques, les tests de fonction pulmonaire et l'intuition clinique du médecin. De plus, un corticostéroïde inhalé en combinaison et un bronchodilatateur inhalé à longue durée d’action devraient être introduits rapidement dans le plan de traitement. La deuxième étude a permis d’évaluer la fréquence des effets indésirables chez les patients MPOC/ACOS traités avec un bronchodilatateur inhalé à longue durée d’action. Cette étude démontre que les effets indésirables sont fréquents chez les patients MPOC/ACOS et que la sécheresse buccale et la gorge sèche sont les plus rapportés. Ces résultats démontrent que la mise en place de lignes directrices pour l’ACOS ainsi qu’une meilleure connaissance du profil de tolérance des bronchodilatateurs inhalés à longue durée d’action seraient bénéfiques pour les patients

Efeitos do treino muscular inspiratório na função pulmonar de basquetebolistas federadas

Projeto de Graduação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Licenciado em Fisioterapia

Assessment of interstitial lung disease in Sjögren’s syndrome by lung ultrasound: a pilot study of correlation with high-resolution chest tomography

The background of this study is to assess the accuracy of lung ultrasound (LUS) to diagnose interstitial lung disease (ILD) in Sjögren’s syndrome (Sjs), in patients who have any alterations in pulmonary function tests (PFT) or respiratory symptoms. LUS was correlated with chest tomography (hrCT), considering it as the imaging gold standard technique to diagnose ILD. This is a pilot, multicenter, cross-sectional, and consecutive-case study. The inclusion criteria are ≥18 years old, Signs and symptoms: according to ACEG 2002 criteria, respiratory symptoms (dyspnea, cough), or any alterations in PFR. LUS was done following the International Consensus Conference on Lung Ultrasound protocol for interstitial syndrome (B pattern). Of the 50 patients in follow-up, 13 (26%) met the inclusion criteria. All were women with age 63.62 years (range 39–88). 78.6% of the cases had primary Sjs (SLE, RA, n = 2). The intra-rater reliability k is 1, according to Gwet’s Ac1 and GI index (probability to concordance—e(K)—, by Cohen, of 0.52). LUS has a sensitivity of 1 (95% CI 0.398–1.0), specificity of 0.89 (95% CI 0.518–0.997), and a positive probability reason of 9.00 (95% CI 7.1–11.3) to detect ILD. The correlation of Pearson is r = 0.84 (p < 0.001). To check the accuracy of LUS to diagnose ILD, a completely bilateral criterion of yes/no for interstitial pattern was chosen, AUC reaches significance, 0.94 (0.07) (95% CI 0.81–1.0, p = 0.014). LUS reaches an excellent correlation to hrCT in Sjs affected with ILD, and might be a useful technique in daily clinical practice for the assessment of pulmonary disease in the sicca syndrome. © 2016 SIMI

Carcinomatosis linfangitica pulmonar

Mujer de 69 años con antecedente de gastrectomía subtotal por adenocarcinoma de estómago (2 años antes), con diagnóstico de carcinomatosis linfangítica pulmonar.

Pulmonary artery thrombosis in experimental Angiostrongylus vasorum infection does not result in pulmonary hypertension and echocardiographic right ventricular changes

BACKGROUND: Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. HYPOTHESIS: A. vasorum-induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. ANIMALS: Six healthy Beagles experimentally inoculated with A. vasorum. METHODS: Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. RESULTS: All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO2 of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. CONCLUSION: In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

1 Hypoxic pulmonary hypertension in rats (10% O-2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 Perindopril (30 mg kg(-1) d(-1)) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5 We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

Post-match changes in neuromuscular function and the relationship to match demands in amateur rugby league matches

Objectives: The current study investigated the change in neuromuscular contractile properties following competitive rugby league matches and the relationship with physical match demands. Design: Eleven trained, male rugby league players participated in 2–3 amateur, competitive matches (n = 30). Methods: Prior to, immediately (within 15-min) and 2 h post-match, players performed repeated counter-movement jumps (CMJ) followed by isometric tests on the right knee extensors for maximal voluntary contraction (MVC), voluntary activation (VA) and evoked twitch contractile properties of peak twitch force (Pt), rate of torque development (RTD), contraction duration (CD) and relaxation rate (RR). During each match, players wore 1 Hz Global Positioning Satellite devices to record distance and speeds of matches. Further, matches were filmed and underwent notational analysis for number of total body collisions. Results: Total, high-intensity, very-high intensity distances covered and mean speed were 5585 ± 1078 m, 661 ± 265, 216 ± 121 m and 75 ± 14 m min−1, respectively. MVC was significantly reduced immediately and 2 h post-match by 8 ± 11 and 12 ± 13% from pre-match (p < 0.05). Moreover, twitch contractile properties indicated a suppression of Pt, RTD and RR immediately post-match (p < 0.05). However, VA was not significantly altered from pre-match (90 ± 9%), immediately-post (89 ± 9%) or 2 h post (89 ± 8%), (p > 0.05). Correlation analyses indicated that total playing time (r = −0.50) and mean speed (r = −0.40) were moderately associated to the change in post-match MVC, while mean speed (r = 0.35) was moderately associated to VA. Conclusions: The present study highlights the physical demands of competitive amateur rugby league result in interruption of peripheral contractile function, and post-match voluntary torque suppression may be associated with match playing time and mean speeds.

Nutritional support and functional capacity in chronic obstructive pulmonary disease: A systematic review and meta-analysis

Currently there is confusion about the value of using nutritional support to treat malnutrition and improve functional outcomes in chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to clarify the effectiveness of nutritional support in improving functional outcomes in COPD. A systematic review identified 12 RCTs (n = 448) in stable COPD patients investigating the effects of nutritional support [dietary advice (1 RCT), oral nutritional supplements (ONS; 10 RCTs), enteral tube feeding (1 RCT)] versus control on functional outcomes. Meta-analysis of the changes induced by intervention found that whilst respiratory function (FEV(1,) lung capacity, blood gases) was unresponsive to nutritional support, both inspiratory and expiratory muscle strength (PI max +3.86 SE 1.89 cm H(2) O, P = 0.041; PE max +11.85 SE 5.54 cm H(2) O, P = 0.032) and handgrip strength (+1.35 SE 0.69 kg, P = 0.05) were significantly improved, and associated with weight gains of ≥ 2 kg. Nutritional support produced significant improvements in quality of life in some trials, although meta-analysis was not possible. It also led to improved exercise performance and enhancement of exercise rehabilitation programmes. This systematic review and meta-analysis demonstrates that nutritional support in COPD results in significant improvements in a number of clinically relevant functional outcomes, complementing a previous review showing improvements in nutritional intake and weight.

A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis

BACKGROUND AND OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a degenerative disease characterized by fibrosis following failed epithelial repair. Mesenchymal stromal cells (MSC), a key component of the stem cell niche in bone marrow and possibly other organs including lung, have been shown to enhance epithelial repair and are effective in preclinical models of inflammation-induced pulmonary fibrosis, but may be profibrotic in some circumstances. METHODS: In this single centre, non-randomized, dose escalation phase 1b trial, patients with moderately severe IPF (diffusing capacity for carbon monoxide (DLCO ) ≥ 25% and forced vital capacity (FVC) ≥ 50%) received either 1 × 10(6) (n = 4) or 2 × 10(6) (n = 4) unrelated-donor, placenta-derived MSC/kg via a peripheral vein and were followed for 6 months with lung function (FVC and DLCO ), 6-min walk distance (6MWD) and computed tomography (CT) chest. RESULTS: Eight patients (4 female, aged 63.5 (57-75) years) with median (interquartile range) FVC 60 (52.5-74.5)% and DLCO 34.5 (29.5-40)% predicted were treated. Both dose schedules were well tolerated with only minor and transient acute adverse effects. MSC infusion was associated with a transient (1% (0-2%)) fall in SaO2 after 15 min, but no changes in haemodynamics. At 6 months FVC, DLCO , 6MWD and CT fibrosis score were unchanged compared with baseline. There was no evidence of worsening fibrosis. CONCLUSIONS: Intravenous MSC administration is feasible and has a good short-term safety profile in patients with moderately severe IPF.