Valutazione delle funzioni cardio-respiratorie ed epatiche in pazienti con cuore univentricolare trattati con intervento di connessione cavo-polmonare totale

L'intervento di connessione cavo-polmonare totale (TCPC) nei pazienti portatori di cuore univentricolare, a causa della particolare condizione emodinamica, determina un risentimento a carico di numerosi parenchimi. Scopo della ricerca è di valutare l'entità di questo danno ad un follow-up medio-lungo. Sono stati arruolati 115 pazienti, sottoposti ad intervento presso i centri di Cardiochirurgia Pediatrica di Bologna (52 pz) e Torino (63 pz). Il follow-up medio è stato di 125±2 mesi. I pazienti sono stati sottoposti ad indagine emodinamica (88 pz), test cardiopolmonare (75 pz) e Fibroscan ed ecografia epatica (47 pz). La pressione polmonare media è stata di 11.5±2.6mmHg, ed in 12 pazienti i valori di pressione polmonare erano superiori a 15mmHg. La pressione atriale media era di 6.7±2.3mmHg ed il calcolo delle resistenze vascolari polmonari indicizzate (RVP) era in media di 2±0.99 UW/m2. In 29 pazienti le RVP erano superiori a 2 UW/m2. La VO2 max in media era pari a 28±31 ml/Kg/min, 58±15 % del valore teorico. La frequenza cardiaca massima all'apice dello sforzo era di 151±22 bpm, pari al 74±17% del valore teorico. Il Fibroscan ha fornito un valore medio di 17.01 kPa (8-34.3kPa). Cinque pazienti erano in classe F2, 9 pazienti in classe F3 e 33 pazienti risultavano in classe F4. Nei pazienti con follow-up maggiore di 10 anni il valore di stiffness epatica (19.6±5.2kPa) è risultato significativamente maggiore a quello dei pazienti con follow-up minore di 10 anni (15.1±5.8kPa, p<0.01). La frequenza cardiaca massima raggiunta durante lo sforzo del test cardiopolmonare è risultata significativamente correlata alla morfologia del ventricolo unico, risultando del 67.8±14.4% del valore teorico nei pazienti portatori di ventricolo destro contro il 79.6±8.7% dei portatori di ventricolo sinistro (p=0.006). L'intervento di TCPC determina un risentimento a carico di numerosi parenchimi proporzionale alla lunghezza del follow-up, e necessita pertanto un costante monitoraggio clinico-strumentale multidisciplinare.

Nocturnal periodic breathing during acclimatization at very high altitude at Mount Muztagh Ata (7,546 m)

Quantitative data on ventilation during acclimatization at very high altitude are scant. Therefore, we monitored nocturnal ventilation and oxygen saturation in mountaineers ascending Mt. Muztagh Ata (7,546 m).

Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration

Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration.

Prognostic importance of hyponatremia in patients with acute pulmonary embolism

Although associated with adverse outcomes in other cardiopulmonary conditions, the prognostic value of hyponatremia, a marker of neurohormonal activation, in patients with acute pulmonary embolism (PE) is unknown.

The Th17 pathway in cystic fibrosis lung disease

Cystic fibrosis (CF) is characterized by bronchoalveolar neutrophilia and submucosal lymphocytosis. We hypothesized that Th17 lymphocytes are part of this submucosal infiltrate.

Alteration of the pulmonary surfactant system in full-term infants with hereditary ABCA3 deficiency

RATIONALE: ABCA3 mutations are known to cause fatal surfactant deficiency. OBJECTIVE: We studied ABCA3 protein expression in full-term newborns with unexplained respiratory distress syndrome (URDS) as well as the relevance of ABCA3 mutations for surfactant homeostasis. METHODS: Lung tissue of infants with URDS was analyzed for the expression of ABCA3 in type II pneumocytes. Coding exons of the ABCA3 gene were sequenced. Surfactant protein expression was studied by immunohistochemistry, immunoelectron microscopy, and Western blotting. RESULTS: ABCA3 protein expression was found to be greatly reduced or absent in 10 of 14 infants with URDS. Direct sequencing revealed distinct ABCA3 mutations clustering within vulnerable domains of the ABCA3 protein. A strong expression of precursors of surfactant protein B (pro-SP-B) but only low levels and aggregates of mature surfactant protein B (SP-B) within electron-dense bodies in type II pneumocytes were found. Within the matrix of electron-dense bodies, we detected precursors of SP-C (pro-SP-C) and cathepsin D. SP-A was localized in small intracellular vesicles, but not in electron-dense bodies. SP-A and pro-SP-B were shown to accumulate in the intraalveolar space, whereas mature SP-B and SP-C were reduced or absent, respectively. CONCLUSION: Our data provide evidence that ABCA3 mutations are associated not only with a deficiency of ABCA3 but also with an abnormal processing and routing of SP-B and SP-C, leading to severe alterations of surfactant homeostasis and respiratory distress syndrome. To identify infants with hereditary ABCA3 deficiency, we suggest a combined diagnostic approach including immunohistochemical, ultrastructural, and mutation analysis.

Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis

RATIONALE: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA. OBJECTIVES: To determine whether serum levels of TARC and MDC characterize ABPA in patients with cystic fibrosis (CF) and to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in patients with CF. METHODS: Levels of TARC and MDC and levels of Th1 (IL-12 and IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines were analyzed in serum of 16 patients with CF with ABPA, six non-CF patients with asthma with ABPA, 13 patients with CF colonized with Aspergillus fumigatus, six patients with CF sensitized to A. fumigatus, 12 atopic patients with CF, and 13 non-CF atopic control subjects by ELISA. The longitudinal course of TARC, MDC, and IgE levels was assessed during ABPA episodes. RESULTS: Patients with ABPA had significantly higher serum levels of TARC compared with the other patient groups. Cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in patients with CF more clearly than IgE levels. In patients with CF and ABPA, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4. CONCLUSIONS: Serum levels of TARC differentiate patients with CF or patients with asthma with ABPA from patients with CF colonized with or sensitized to A. fumigatus, atopic patients with CF, and atopic control subjects. Longitudinally, levels of TARC indicate ABPA exacerbations, suggesting TARC as a marker for identification and monitoring of ABPA in patients with CF.

Chronic rhinoviral infection in lung transplant recipients

RATIONALE: Lung transplant recipients are particularly at risk of complications from rhinovirus, the most frequent respiratory virus circulating in the community. OBJECTIVES: To determine whether lung transplant recipients can be chronically infected by rhinovirus and the potential clinical impact. METHODS: We first identified an index case, in which rhinovirus was isolated repeatedly, and conducted detailed molecular analysis to determine whether this was related to a unique strain or to re-infection episodes. Transbronchial biopsies were used to assess the presence of rhinovirus in the lung parenchyma. The incidence of chronic rhinoviral infections and potential clinical impact was assessed prospectively in a cohort of 68 lung transplant recipients during 19 mo by screening of bronchoalveolar lavages. MEASUREMENTS AND MAIN RESULTS: We describe 3 lung transplant recipients with graft dysfunctions in whom rhinovirus was identified by reverse transcriptase-polymerase chain reaction in upper and lower respiratory specimens over a 12-mo period. In two cases, rhinovirus was repeatedly isolated in culture. The persistence of a unique strain in each case was confirmed by sequence analysis of the 5'NCR and VP1 gene. In the index case, rhinovirus was detected in the lower respiratory parenchyma. In the cohort of lung transplant recipients, rhinoviral infections were documented in bronchoalveolar lavage specimens of 10 recipients, and 2 presented with a persistent infection. CONCLUSIONS: Rhinoviral infection can be persistent in lung transplant recipients with graft dysfunction, and the virus can be detected in the lung parenchyma. Given the potential clinical impact, chronic rhinoviral infection needs to be considered in lung transplant recipients.

Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell-mediated graft-versus-host disease

RATIONALE: Pulmonary complications of hematopoietic stem cell transplantation include infections and graft-versus-host diseases, such as idiopathic pneumonia syndrome (IPS). Conflicting data exist regarding the role of the interferon (IFN)-gamma-producing Th1 CD4(+) T-cell subset and IL-17A in IPS. OBJECTIVES: To determine the role of IFN-gamma and IL-17A in the establishment of pulmonary graft-versus-host disease. METHODS: A semiallogeneic murine model based on C57BL/6 x BALB/c as recipients with transplantation of BALB/c RAG2(-/-) bone marrow and transfer of different genetic knockout T cells (T-bet(-/-), IFN-gamma(-/-), IFN-gammaR(-/-)) on a BALB/c background. Lung tissue was examined for parenchymal changes and infiltrating cells by histology and fluorescence-activated cell sorter analysis. MEASUREMENTS AND MAIN RESULTS: After transfer of semiallogeneic bone marrow together with donor CD4(+) T cells lacking IFN-gamma or T-bet-a T-box transcription factor controlling Th1 commitment-we found severe inflammation in the lungs, but no enhancement in other organs. In contrast, wild-type donor CD4(+) T cells mediated minimal inflammation only, and donor CD8(+) T cells were not required for IPS development. Mechanistically, the absence of IFN-gamma or IFN-gamma signaling in pulmonary parenchymal cells promoted expansion of IL-17A-producing CD4(+) T cells and local IL-17A release. In vivo depletion of IL-17A reduced disease severity. CONCLUSIONS: One mechanism of IFN-gamma protection against IPS is negative regulation of the expansion of pathogenic IL-17A-producing CD4(+) T cells through interaction with the IFN-gamma receptor on the pulmonary parenchymal cell population.

Perioperative anaesthetic management of mediastinal mass in adults

Mediastinal mass syndrome remains an anaesthetic challenge that cannot be underestimated. Depending on the localization and the size of the mediastinal tumour, the clinical presentation is variable ranging from a complete lack of symptoms to severe cardiorespiratory problems. The administration of general anaesthesia can be associated with acute intraoperative or postoperative cardiorespiratory decompensation that may result in death due to tumour-related compression syndromes. The role of the anaesthesiologist, as a part of the interdisciplinary treatment team, is to ensure a safe perioperative period. However, there is still no structured protocol available for perioperative anaesthesiological procedure. The aim of this article is to summarize the genesis of and the diagnostic options for mediastinal mass syndrome and to provide a solid detailed methodology for its safe perioperative management based on a review of the latest literature and our own clinical experiences. Proper anaesthetic management of patients with mediastinal mass syndrome begins with an assessment of the preoperative status, directed foremost at establishing the localization of the tumour and on the basis of the clinical and radiological findings, discerning whether any vital mediastinal structures are affected. We have found it helpful to assign 'severity grade' (using a three-grade clinical classification scale: 'safe', 'uncertain', 'unsafe'), whereby each stage triggers appropriate action in terms of staffing and apparatus, such as the provision of alternatives for airway management, cardiopulmonary bypass and additional specialists. During the preoperative period, we are guided by a 12-point plan that also takes into account the special features of transportation into the operating theatre and patient monitoring. Tumour compression on the airways or the great vessels may create a critical respiratory and/or haemodynamic situation, and therefore the standard of intraoperative management includes induction of anaesthesia in the operating theatre on an adjustable surgical table, the use of short-acting anaesthetics, avoidance of muscle relaxants and maintenance of spontaneous respiration. In the case of severe clinical symptoms and large mediastinal tumours, we consider it absolutely essential to cannulate the femoral vessels preoperatively under local anaesthesia and to provide for the availability of cardiopulmonary bypass in the operating theatre, should extracorporeal circulation become necessary. The benefits of establishing vascular access under local anaesthesia clearly outweigh any associated degree of patient discomfort. In the case of patients classified as 'safe' or 'uncertain', a preoperative consensus with the surgeons should be reached as to the anaesthetic approach and the management of possible complications.

Haptische, visuelle und olfaktorische Sprachen: Westnilotische Wahrnehmungen

Cet article traite des expressions de la perception sensuelle de l’ouest nilotique. La première partie de l’article présente une terminologie ophrésiologique en louo et burun et démontre que cette catégorie lexicale détient aussi une catégorie grammaticale particulière. Phénomènes très rares dans les langues du monde, les termes ophrésiologiques sont seulement présentés sous forme introductive pour encourager davantage les recherches futures. La seconde partie de l’article porte sur les descriptions des couleurs utilisées pour les animaux domestiques. Quand les modalités de l’économie changent, les noms utilisés pour les couleurs des animaux peuvent aussi être employés pour d’autres concepts culturels. La troisième partie de l’article montre que les classificateurs nominaux en mabaan (burun) expriment des principes concernant le toucher en tant que structure cognitive. En conséquence, différents procédés de grammaticalisation sont assumés et corrélés avec des ponctuations dans l’histoire culturelle et mentale des ancêtres des locuteurs de l’ouest nilotique.

Porcine ulcerative dermatitis syndrome in sows: a form of vesicular cutaneous lupus erythematosus?

Severe ulcerative lesions were observed in the skin of two sows in a herd of 540 hybrid sows. Annular to polycyclic, severe crusting dermal ulcerations were found on the abdomen and flanks; moderate lesions were also found at the base of the tail and on the perineum. The lesions were histologically characterised as cell-poor interface dermatitis and folliculitis, basal cell vacuolisation, vesicle formation at the dermal-epidermal junction and serocellular crusts. A subepidermal mild to moderate band, characterised as a mixed inflammatory infiltrate, was present. A test for antinuclear antibodies was negative; however, immunofluorescence testing revealed a linear pattern of IgG precipitation in the skin. Staphylococcus hyicus was demonstrated in the serocellular crusts of one sow. Treatment with antibiotics, topical antiseptics and corticosteroids did not improve the sows' condition. Porcine circovirus and porcine respiratory and reproductive syndrome virus were not isolated from samples taken at postmortem examination. The observed gross lesions, the absence of response to treatment and the exclusion of other skin diseases suggested that the sows were affected with porcine ulcerative dermatitis syndrome.