Novel FOXF1 Mutations in Sporadic and Familial Cases of Alveolar Capillary Dysplasia with Misaligned Pulmonary Veins Imply a Role for its DNA Binding Domain.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a rare and lethal developmental disorder of the lung defined by a constellation of characteristic histopathological features. Nonpulmonary anomalies involving organs of gastrointestinal, cardiovascular, and genitourinary systems have been identified in approximately 80% of patients with ACD/MPV. We have collected DNA and pathological samples from more than 90 infants with ACD/MPV and their family members. Since the publication of our initial report of four point mutations and 10 deletions, we have identified an additional 38 novel nonsynonymous mutations of FOXF1 (nine nonsense, seven frameshift, one inframe deletion, 20 missense, and one no stop). This report represents an up to date list of all known FOXF1 mutations to the best of our knowledge. Majority of the cases are sporadic. We report four familial cases of which three show maternal inheritance, consistent with paternal imprinting of the gene. Twenty five mutations (60%) are located within the putative DNA-binding domain, indicating its plausible role in FOXF1 function. Five mutations map to the second exon. We identified two additional genic and eight genomic deletions upstream to FOXF1. These results corroborate and extend our previous observations and further establish involvement of FOXF1 in ACD/MPV and lung organogenesis.

A 3-step therapeutic strategy for severe alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of lipoproteinaceous material in the terminal airways. Whole lung lavage (WLL) remains the gold standard treatment but may be particularly challenging in cases of severe hypoxemia. We present a 3-step strategy that was used in a patient with PAP-associated refractory hypoxemia and that combined venovenous extracorporeal membrane oxygenation (vvECMO), double-lumen orotracheal intubation, and bilateral multisegmental sequential lavage (MSL). The procedure was well tolerated and permitted weaning from the ventilator.

CARCINOMA BRONQUÍOLO-ALVEOLAR: ASPECTOS NA TOMOGRAFIA COMPUTADORIZADA DE ALTA RESOLUÇÃO

O carcinoma bronquíolo-alveolar é um tipo de carcinoma broncogênico de crescimento insidioso, que surge nas paredes das vias aéreas distais e se dissemina utilizando o septo alveolar como um estroma, preservando a arquitetura pulmonar. Neste trabalho foram analisadas as tomografias computadorizadas de alta resolução de 17 pacientes com carcinoma bronquíolo-alveolar. Ao contrário do relatado na literatura, foram observados predomínio no sexo masculino (71%) e maior freqüência da associação das formas de consolidação e multinodular (53%) em relação à forma nodular solitária (12%), multinodular (12%) e de consolidação (23%). Os aspectos mais encontrados foram: áreas de consolidação (76%), broncograma aéreo (71%), áreas de baixa atenuação provavelmente devidas à presença de muco (60%), espessamento de septos interlobulares, opacidades em vidro fosco e nódulos confluentes (54% cada), e pavimentação em mosaico (36%). Os nódulos cavitados, a atelectasia, o sinal do halo e o aspecto de "árvore em brotamento" foram observados em apenas um caso cada.

Microlitíase alveolar pulmonar em gêmeos univitelinos: relato de dois casos

Os autores apresentam dois casos de microlitíase alveolar pulmonar em gêmeos monozigóticos. Os principais achados obtidos em exames radiográficos e de tomografia computadorizada (técnica de alta resolução) são enfatizados, com base em breve revisão literária.

Comparative study of two needle models in terms of deflection during inferior alveolar nerve block

Objectives: The purpose of this study is to determine the possible differences in deflection between two needles of same length and external gauge but with different internal gauges during truncal block of the inferior alveolar nerve. The initial working hypothesis was that greater deflection may be expected with larger internal gauge needles. Study design: Four clinicians subjected 346 patients to inferior alveolar nerve block and infiltrating anesthesia of the buccal nerve trajectory for the surgical or conventional extraction of the lower third molar. A nonautoaspirating syringe system with 2 types of needle was used: a standard 27-gauge x 35-mm needle with an internal gauge of 0.215 mm or an XL Monoprotect® 27-gauge x 35-mm needle with an internal gauge of 0.265 mm. The following information was systematically recorded for each patient: needle type, gender, anesthetic technique (direct or indirect truncal block) and the number of bone contacts during the procedure, the patient-extraction side, the practitioner performing the technique, and blood aspiration (either positive or negative). Results: 346 needles were used in total. 190 were standard needles (27-gauge x 35-mm needle with an internal gauge of 0.215 mm) and 156 were XL Monoprotect®. Incidence of deflection was observed in 49.1% of cases (170 needles) where 94 were standard needles and 76 XL Monoprotect®. Needle torsion ranged from 0º and 6º. Conclusions: No significant differences were recorded in terms of deflection and internal gauge, operator, patient-extraction side, the anesthetic technique involved and the number of bone contacts during the procedure

Outcomes After Liver Resection for Hepatic Alveolar Echinococcosis: A Single-Center Cohort Study.

BACKGROUND: Switzerland is a region in which alveolar echinococcosis (AE) is endemic. Studies evaluating outcomes after liver resection (LR) for AE are scarce. The aim of this study was to assess the short- and long-term outcomes of AE patients after LR in a single tertiary referral center. METHODS: We retrospectively analyzed data pertaining to all patients with liver AE who were treated with LR at our institution between January 1992 and December 2013. Patient demographics, intraoperative data, extent of LR procedures (major vs. minor LR), postoperative outcomes, and negative histological margin (R0) resection rate were recorded in a database. Recurrence rates after LR were analyzed. RESULTS: LR was performed in 59 patients diagnosed with hepatic AE (56 complete surgeries, 3 reduction surgeries). Postoperative morbidity and mortality were observed in 34 % (25 % grade I-II, 9 % grade III-IV) and 2 % of the patients, respectively. R0 (complete) resection rate was 71 % (n = 42), and R1/R2 resection rate was 29 % (n = 17). Extra-hepatic recurrence occurred in 1 case (lung) after R0 resection. In cases of R1/R2 resection, 7 intra-hepatic disease progressions occurred with a median time of 10 months (IQR 6-11 months). Long-term (more than 1 year) benzimidazole treatment stabilized the disease in 64 % (9/14) of patients with R1 status. The overall survival rate was 97 %. CONCLUSIONS: Liver AE can be safely and definitively treated with LR, provided that R0 resection is achieved. In cases of R1 resection, benzimidazole therapy seems to be effective in stabilizing the intra-hepatic disease and preventing extra-hepatic recurrence.

Regressão espontânea de proteinose alveolar pulmonar: relato de caso

Relatamos o caso de uma mulher de 21 anos com história de seis meses de dispneia progressiva, tosse seca e perda de peso. A tomografia computadorizada de alta resolução revelou padrão de pavimentação em mosaico com áreas focais poupadas. A paciente foi submetida a biópsia pulmonar transbrônquica, que confirmou o diagnóstico de proteinose alveolar. Dois anos depois, sem tratamento, houve importante melhora das opacidades pulmonares.

Can chest high-resolution computed tomography findings diagnose pulmonary alveolar microlithiasis?

AbstractObjective:The present study was aimed at retrospectively reviewing high-resolution computed tomography (HRCT) findings in patients with pulmonary alveolar microlithiasis in order to evaluate the frequency of tomographic findings and their distribution in the lung parenchyma.Materials and Methods:Thirteen patients (9 females and 4 males; age, 9 to 59 years; mean age, 34.5 years) were included in the present study. The HRCT images were independently evaluated by two observers whose decisions were made by consensus. The inclusion criterion was the presence of abnormalities typical of pulmonary alveolar microlithiasis at HRCT, which precludes lung biopsy. However, in 6 cases lung biopsy was performed.Results:Ground-glass opacities and small parenchymal nodules were the predominant tomographic findings, present in 100% of cases, followed by small subpleural nodules (92.3%), subpleural cysts (84.6%), subpleural linear calcifications (69.2%), crazy-paving pattern (69.2%), fissure nodularity (53.8%), calcification along interlobular septa (46.2%) and dense consolidation (46.2%).Conclusion:As regards distribution of the lesions, there was preferential involvement of the lower third of the lungs. No predominance of distribution in axial and anteroposterior directions was observed.

Barrier-protective effects of activated protein C in human alveolar epithelial cells

Acute lung injury (ALI) is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC) on mechanical tension and barrier integrity in human alveolar epithelial cells (A549) exposed to thrombin. Cells were pretreated for 3 h with APC (50 mg/ml) or vehicle (control). Subsequently, thrombin (50 nM) or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

Pregabalin in the treatment of inferior alveolar nerve paraesthesia following overfilling of endodontic sealer

A case of orofacial pain and inferior alveolar nerve (IAN) paraesthesia after extrusion of endodontic sealer within the mandibular canal treated with prednisone and pregabalin is described. A 36-year-old woman underwent root canal treatment of the mandibular second right premolar tooth. Post-operative panoramic radiograph revealed the presence of radiopaque canal sealer in the mandibular canal. Damage to IAN consecutive to extrusion of endodontic sealer was diagnosed. Non-surgical management was decided, including: 1 mg/kg/day prednisone 2 times/day, once-daily regimen, and 150 mg/day pregabalin, two doses per day, monitoring the progress with periodic follow-up visits. Six weeks after the incident the signs and symptoms were gone. The complete resolution of paraesthesia and the control of pain achieved suggest that a non-surgical approach, combining prednisone and the GABA analogue pregabalin, is a good option in the management of the IAN damage subsequent to endodontic sealer extrusion