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Sample records for nitrofen-induced hypoplastic lungs

  1. Effect of nitric oxide on the development of nitrofen-induced fetal hypoplastic lung explants.

    PubMed

    Shinkai, Masato; Shinkai, Toko; Pirker, Martina E; Montedonico, Sandra; Puri, Prem

    2005-01-01

    Nitric oxide (NO) is an important cell-signaling molecule, and its generators, nitric oxide synthases, are expressed temporospatially in fetal rat lung. Recently, NO has been reported to modulate branching of the fetal rat lung lobe in vitro. We designed this study to evaluate the effect of NO on the morphogenesis of hypoplastic lung using nitrofen-induced rat lung explant model. A hypoplastic fetal lung model and a normal control lung model were induced by feeding a pregnant rat with nitrofen (100 mg) or olive oil on day 9.5 of gestation, respectively. Fetal lungs were harvested on day 13.5 and placed in organ culture containing serum-free medium Dulbecco modified Eagle medium. An NO donor, DETA NONOate (DETA/NO), was added daily in the culture medium. The lung cultures were divided into 4 groups: group 1 (n = 8), normal controls without DETA/NO; group 2 (n = 22), normal controls with DETA/NO; group 3 (n = 13), hypoplastic lungs without DETA/NO; group 4 (n = 22), hypoplastic lungs with DETA/NO. The fetal lungs were incubated for 48 hours at 37 degrees C with 5% CO2. Lung bud count and area of the specimens were measured under computer-assisted digital tracings. The rate of increase in bud count and lung area was calculated as the ratio of each value at 48 hours minus each value at 0 hour, divided by the value at 0 hour. The lung bud count was significantly increased in group 2 compared with group 1 at a concentration of 50 micromol/L DETA/NO (P < .05). In the nitrofen group, the lung bud count was significantly increased in group 4 compared with group 3 at 100 micromol/L DETA/NO added (P < .05). There was no significant difference in the rate of increase in whole lung area among the 4 groups. The peak increase rates of lung area and bud count were significantly lower in group 4 compared with group 2. This study demonstrates that the NO donor, DETA/NO, promotes branching of the nitrofen-induced hypoplastic fetal lung explant. These data suggest that NO may modulate

  2. Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.

    PubMed

    Takahashi, Hiromizu; Friedmacher, Florian; Fujiwara, Naho; Hofmann, Alejandro; Kutasy, Balazs; Gosemann, Jan-Hendrik; Puri, Prem

    2013-11-01

    Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.

  3. Expression of T-box transcription factors 2, 4 and 5 is decreased in the branching airway mesenchyme of nitrofen-induced hypoplastic lungs.

    PubMed

    Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

    2017-02-01

    Pulmonary hypoplasia (PH), characterized by smaller lung size and reduced airway branching, remains a major therapeutic challenge in newborns with congenital diaphragmatic hernia (CDH). T-box transcription factors (Tbx) have been identified as key components of the gene network that regulates fetal lung development. Tbx2, Tbx4 and Tbx5 are expressed throughout the mesenchyme of the developing lung, regulating the process of lung branching morphogenesis. Furthermore, lungs of Tbx2-, Tbx4- and Tbx5-deficient mice are hypoplastic and exhibit decreased lung branching, similar to PH in human CDH. We hypothesized that the expression of Tbx2, Tbx4 and Tbx5 is decreased in the branching airway mesenchyme of hypoplastic rat lungs with nitrofen-induced CDH. Time-mated rats received either nitrofen or vehicle on gestational day 9 (D9). Fetuses were killed on D15, D18 and D21, and dissected lungs were divided into control and nitrofen-exposed specimens. Pulmonary gene expression of Tbx2, Tbx4 and Tbx5 was investigated by quantitative real-time polymerase chain reaction. Immunofluorescence double staining for Tbx2, Tbx4 and Tbx5 was combined with the mesenchymal marker Fgf10 to assess protein expression and localization in branching airway tissue. Relative mRNA levels of Tbx2, Tbx4 and Tbx5 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Confocal laser scanning microscopy showed markedly diminished immunofluorescence of Tbx2, Tbx4 and Tbx5 in mesenchymal cells surrounding branching airways of nitrofen-exposed fetuses on D15, D18 and D21 compared to controls. Decreased expression of Tbx2, Tbx4 and Tbx5 in the pulmonary mesenchyme during fetal lung development may lead to a decrease or arrest of airway branching, thus contributing to PH in the nitrofen-induced CDH model.

  4. NKCC-1 and ENaC are down-regulated in nitrofen-induced hypoplastic lungs with congenital diaphragmatic hernia.

    PubMed

    Ringman, Andreas; Zelenina, Marina; Eklöf, Ann-Christine; Aperia, Anita; Frenckner, Björn

    2008-09-01

    Congenital diaphragmatic hernia (CDH) is accompanied by pulmonary hypoplasia and pulmonary hypertension. Fetal lung growth is dependent on the secretion of lung liquid, which normally is absorbed at partus. The ion channel NKCC-1 is involved in this secretory process, but has recently also been reported to be implicated in absorption. CDH patients show a disturbed transition from secretion to absorption. alpha- and beta-ENaC are essential for lung liquid absorption. Common for all transcellular ion transport is the need for Na/K-ATPase as a primary driving force. The aim of the study was first to map the normal pulmonary expression of the above proteins during late gestation and secondly to see if the expression was affected in a CDH rat model. Pregnant Sprague-Dawley rat dams were given nitrofen on gestational day 9.5 to induce CDH. The fetuses were removed on gestational days E18 and E21. In addition, newborn rats were harvested postpartum on day P2. The fetuses were put into one of two groups: hypoplastic lungs without CDH (N-CDH) and hypoplastic lungs with CDH (N+CDH). The pulmonary expression of NKCC-1, alpha-/beta-ENaC and Na/K-ATPase was then analyzed using Western blot. We found that the protein levels of NKCC-1 on gestational days E18 and E21 were significantly lower among fetuses with N+CDH as well as N-CDH compared to controls. The expression of beta-ENaC was also significantly down-regulated in both the groups on E18 and E21. The protein levels of alpha-ENaC and Na/K-ATPase were not found to be significantly decreased, but both showed a tendency towards down-regulation. The marked down-regulation of NKCC-1 in fetal hypoplastic lungs with CDH indicates a possibly decreased lung liquid production. This may be one of the mechanisms behind the disturbed pulmonary development in CDH. We also show that beta-ENaC is down-regulated. Down-regulation of beta-ENaC may result in abnormal lung liquid absorption, which could be one of the mechanisms behind the

  5. [Effect of tetrandrine on endothelin expression in the lungs and clinical significance thereof: experiment with rat models with nitrofen-induced congenital diaphragmatic hernia].

    PubMed

    Xiong, Zhong-Xun; Liu, Wen-Ying; Wang, Yong-Gang; Xu, Chang; Chen, Zhong-Xian

    2007-02-06

    To investigate the effects of tetrandrine on endothelin expression in the lungs and its clinical significance. 25 pregnant female SD rats were randomly divided into 5 equal groups: Groups A to D were fed with nitrofen to cause congenital diaphragmatic hernia (CDH) in the fetuses. Group A was injected with normal saline, Group B with dexamethasone (DXM), Group C with tetrandrine, and Group D with DXM + tetrandrine. Group E was control Group. On day 21.5 of pregnancy the fetuses were delivered by cesarean section and killed. Microscopy was used to observe the CDH formation, and the relative wall thickness (RWA) and relative wall area (RWA) of pulmonary arterioles. The lung/body weight ratio, and relative integrated optical density (IOD) of pulmonary arteriole and bronchiole were observed. The expression of endothelin in the lung tissues was detected by immunohistochemistry. 9 rats of Group A-D produced 57 fetuses with CDH with a CDH arte of 45.2%. The lung/body weight ratios, and RWA values of Group A-D were all significantly lower than that of Group E (all P < 0.05). The RWT of pulmonary arteriole was significantly lower in Groups B and C compared with Group E (both P < 0.05). The RWT and RWA of Group A were significantly lower than those of Group B-D (all P < 0.05). The values of relative IOD of pulmonary tissues and of pulmonary arteriole of Group A-D were all significantly lower than those of Group E (all P < 0.05). A positive correlation existed between the relative IOD of endothelin in pulmonary arteriole and in bronchiole (P < 0.01), and among the RWT and RWA of pulmonary arteriole, and relative IOD (all P < 0.01). Tetrandrine improves the pulmonary hypoplasia and degrades the pulmonary hypertension.

  6. Prenatal exposure to nitrofen induces Fryns phenotype in mice.

    PubMed

    Acosta, J M; Chai, Y; Meara, J G; Bringas, P; Anderson, K D; Warburton, D

    2001-06-01

    Prenatal exposure to nitrofen is known to cause multiple malformations in mice. The reported malformations include lung hypoplasia, diaphragmatic hernia, cardiovascular defects, skeletal malformations, cleft palate, and renal abnormalities. The authors present detailed findings of craniofacial defects after prenatal exposure to nitrofen, and propose that together with the previously reported malformations, nitrofen exposure induces a Fryns phenotype in mice. Fryns syndrome is a rare human genetic syndrome that is an autosomal recessive disorder characterized by lung hypoplasia, diaphragmatic hernia, craniofacial malformations, skeletal malformations, cardiovascular malformations, and genitourinary malformations. Timed-pregnant Swiss Webster mice were gavage-fed 25 mg of nitrofen on day 8 of gestation. Control animals received olive oil. Osteogenesis and chondrogenesis were studied in fetuses recovered on day 17 after Alcian blue-Alizarin red staining. Approximately 26% of the nitrofen-exposed embryos had severe craniofacial defects, and there was generalized delay in chondrogenesis and osteogenesis throughout the skeleton. No such defects were noted in the control group. The authors propose that prenatal exposure to nitrofen induces a Fryns phenotype in mice, and thus speculate that nitrofen may target similar molecular mechanisms to those that lead to Fryns syndrome.

  7. Neuroendocrine factors regulate retinoic acid receptors in normal and hypoplastic lung development

    PubMed Central

    Pereira-Terra, Patrícia; Moura, Rute S; Nogueira-Silva, Cristina; Correia-Pinto, Jorge

    2015-01-01

    Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague–Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ. Key points Retinoic acid (RA) and ghrelin levels are altered in human hypoplastic lungs when compared to healthy lungs. Although considerable data have been obtained about RA, ghrelin and bombesin in the congenital

  8. MDCT and 3D evaluation of type 2 hypoplastic pulmonary artery sling associated with right lung agenesis, hypoplastic aortic arch, and long segment tracheal stenosis.

    PubMed

    Lee, Edward Y

    2007-11-01

    The early diagnosis and complete anatomic evaluation of pulmonary artery sling, a congenital vascular anomaly in which left pulmonary artery arises from the right pulmonary artery, is paramount for proper patient management, because patients with this disorder frequently have other congenital anomalies resulting in high morbidity and mortality. Until recently, pulmonary artery sling in the neonate has been established with standard radiologic imaging studies such as plain radiographs, barium swallow studies, fluoroscopy-guided airway studies, and echocardiograms. However, with the development and widespread availability of multidetector computed tomography, pulmonary artery sling is increasingly evaluated with this newer technology. This case report presents a rare incidence of type 2 hypoplastic pulmonary artery sling in a neonate associated with right lung agenesis, hypoplastic aortic arch, and long segment tracheal stenosis. Multidetector computed tomography combined with 3-dimensional evaluation was particularly helpful in making a correct diagnosis of the complicated anatomic anomalies found in this case.

  9. Massive Bochdalek diaphragmatic hernia in adult with hypoplastic lung.

    PubMed

    Karamustafaoglu, Yekta Altemur; Yoruk, Yener; Kuzucuoglu, Mustafa; Yanik, Fazli

    2015-05-01

    Bochdalek diaphragmatic hernia is generally congenital and rarely diagnosed incidentally in adults. A 21-year-old man presented with a diaphragmatic hernia suspected during routine examination. Chest radiography showed the colon and small intestine herniating into the left hemithorax and the ileocecal appendix in the superior thoracic apertura. We performed a thoracoabdominal incision and the stomach, omentum, colon, and small intestine were retracted back into the abdomen. The diaphragm was repaired with Prolene mesh following adhesiolysis. Two months later, there was no recurrence but no lung expansion. The space was filled with effusion, but the patient had no complaints. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  10. Cortisol enhances structural maturation of the hypoplastic fetal lung in sheep

    PubMed Central

    Boland, Rochelle; Joyce, Belinda J; Wallace, Megan J; Stanton, Heather; Fosang, Amanda J; Pierce, Richard A; Harding, Richard; Hooper, Stuart B

    2004-01-01

    Although exogenous corticosteroids advance structural maturation of the fetal lung, they can adversely affect fetal lung and body growth. Our aim was to determine whether cortisol, at physiological doses, can enhance structural maturation of the hypoplastic fetal lung without affecting fetal lung growth. Fetal sheep were divided into four groups (n = 5 for each) and lung hypoplasia (LH) was induced in two groups. Increasing doses of cortisol (1.5–4.0 mg) were infused into one group of fetuses with LH and one group without LH; the other two groups received saline. LH retarded structural development, reduced tropoelastin mRNA levels, reduced hydroxyproline and elastin contents, and increased active matrix metalloproteinase-2 (MMP-2) levels in the fetal lung. Cortisol infusions had no effect on fetal lung growth or body weights. In fetuses with LH, cortisol increased the percentage airspace, reduced the interalveolar wall thickness, increased alveolar number and reduced the increase in active MMP-2 levels. Thus, relatively low doses of cortisol can enhance structural maturation of the fetal lung without adversely affecting fetal lung growth. However, cortisol did not correct the abnormal deposition of elastin within the alveolar parenchyma associated with LH, indicating that secondary septal crest formation remained abnormal. PMID:14578477

  11. Pregnancy with hypoplastic left lung complicated by pneumothorax and pulmonary embolism.

    PubMed

    Zainudin, Lily D; Abdul Hafidz, Muhammad I; Zakaria, Ahmad F; Mohd Zim, Mohd A; Ismail, Ahmad I; Abdul Rani, Mohammed F

    2016-03-01

    We report a case of a 34-year-old lady with past history of asthma and pulmonary tuberculosis, who presented 5 weeks pregnant with acute dyspnea. Her chest X-ray showed left-sided complete lung collapse and concomitant right-sided pneumothorax. The pneumothorax was initially managed conservatively with a chest tube but due to its persistence despite suction, was subsequently changed to a Pneumostat(TM), with which she was later discharged. She had a normal echocardiography (ejection fraction [EF] 67%) at 5 weeks of gestation but developed pulmonary hypertension (EF 55%, pulmonary arterial pressure 40.7 mmHg) as the pregnancy progressed. She delivered a healthy baby at 35 weeks via elective lower section caesarean section with spinal anesthesia. We followed her up postnatally and noted the presence of left-sided pulmonary embolism, hypoplastic left lung, and left pulmonary artery. The management of this complex case involved a multidisciplinary effort between general medical, respiratory, obstetric, and cardiothoracic teams.

  12. Hypoplastic left heart syndrome and the nutmeg lung pattern in utero: a cause and effect relationship or prognostic indicator?

    PubMed

    Saul, David; Degenhardt, Karl; Iyoob, Suzanne D; Surrey, Lea F; Johnson, Ann M; Johnson, Mark P; Rychik, Jack; Victoria, Teresa

    2016-04-01

    Hypoplastic left heart syndrome (HLHS) is the third most common cause of critical congenital heart disease in newborns, and one of the most challenging forms to treat. Secondary pulmonary lymphangiectasia has been recognized in association with HLHS, an appearance described on fetal MRI as the "nutmeg lung." To investigate the association of fetal nutmeg lung with HLHS survival. A retrospective search of the fetal MRI database was performed. The nutmeg lung pattern was defined as T2 heterogeneous signal with tubular structures radiating peripherally from the hila. Postnatal echocardiograms and charts were reviewed. Forty-four fetal MR studies met inclusion criteria, of which 4 patients (9%) had the nutmeg lung pattern and 3 of whom also had restrictive lesions. Mortality in this nutmeg lung group was 100% by 5 months of age. Of the 40 patients without nutmeg lung, mortality/orthotopic heart transplant (OHT) was 35%. Of these 40 patients without nutmeg lung, 5 had restriction on echo, 3 of whom died/had OHT before 5 months of age (60% of patients with restriction and non-nutmeg lung). There was a significantly higher incidence of restrictive lesions (P = 0.02) and mortality/OHT (P = 0.02) in patients with nutmeg lung compared to those without. The nutmeg lung MR appearance in HLHS fetuses is associated with increased mortality/OHT (100% in the first 5 months of life compared to 35% with HLHS alone). Not all patients with restrictive lesions develop nutmeg lung, and outcome is not as poor when restriction is present in isolation. Dedicated evaluation for nutmeg lung pattern on fetal MR studies may be useful to guide prognostication and aid clinicians in counseling parents of fetuses with HLHS.

  13. Hypoplastic left heart syndrome

    MedlinePlus

    HLHS; Congenital heart - hypoplastic left heart; Cyanotic heart disease - hypoplastic left heart ... Hypoplastic left heart is a rare type of congenital heart disease. It is more common in males than in females. As ...

  14. Mesenchymal expression of the FRAS1/FREM2 gene unit is decreased in the developing fetal diaphragm of nitrofen-induced congenital diaphragmatic hernia.

    PubMed

    Takahashi, Toshiaki; Friedmacher, Florian; Zimmer, Julia; Puri, Prem

    2016-02-01

    Developmental mutations that inhibit normal formation of extracellular matrix (ECM) in fetal diaphragms have been identified in congenital diaphragmatic hernia (CDH). FRAS1 and FRAS1-related extracellular matrix 2 (FREM2), which encode important ECM proteins, are secreted by mesenchymal cells during diaphragmatic development. The FRAS1/FREM2 gene unit has been shown to form a ternary complex with FREM1, which plays a crucial role during formation of human and rodent diaphragms. Furthermore, it has been demonstrated that the diaphragmatic expression of FREM1 is decreased in the nitrofen-induced CDH model. We hypothesized that FRAS1 and FREM2 expression is decreased in the developing diaphragms of fetal rats with nitrofen-induced CDH. Pregnant rats were exposed to either nitrofen or vehicle on gestational day 9 (D9), and fetuses were harvested on D13, D15 and D18. Microdissected diaphragms were divided into nitrofen-exposed/CDH and control samples (n = 12 per time-point and experimental group, respectively). Diaphragmatic gene expression levels of FRAS1 and FREM2 were analyzed by qRT-PCR. Immunofluorescence double staining for FRAS1 and FREM2 was combined with the mesenchymal marker GATA4 in order to evaluate protein expression and localization in pleuroperitoneal folds (PPFs) and fetal diaphragmatic tissue. Relative mRNA expression of FRAS1 and FREM2 were significantly reduced in PPFs of nitrofen-exposed fetuses on D13 (1.76 ± 0.86 vs. 3.09 ± 1.15; p < 0.05 and 0.47 ± 0.26 vs. 0.82 ± 0.36; p < 0.05), developing diaphragms of nitrofen-exposed fetuses on D15 (1.45 ± 0.80 vs. 2.63 ± 0.84; p < 0.05 and 0.41 ± 0.16 vs. 1.02 ± 0.49; p < 0.05) and fully muscularized diaphragms of CDH fetuses on D18 (1.35 ± 0.75 vs. 2.32 ± 0.92; p < 0.05 and 0.37 ± 0.24 vs. 0.70 ± 0.32; p < 0.05) compared to controls. Confocal laser scanning microscopy revealed markedly diminished FRAS1 and FREM2 immunofluorescence in diaphragmatic

  15. Hypoplastic left heart syndrome (image)

    MedlinePlus

    Hypoplastic left heart syndrome is a congenital heart condition that occurs during the development of the heart in the ... womb. During the heart's development, parts of the left side of the heart (mitral valve, left ventricle ...

  16. Fontan Operation in a Patient with Severe Hypoplastic Right Pulmonary Artery, Single Ventricle, and Heterotaxy Syndrome

    PubMed Central

    Pan, Jun-Yen; Lin, Chu-Chuan; Chang, Jen-Ping

    2016-01-01

    Assessment of the pulmonary circulation status including pressure, resistance, size, and absence of anatomical distortion, is crucial to the successful Fontan operation. Most patients are found to have acceptable pulmonary arteries after previous palliation, although some degree of distortion is not uncommon. However, in rare instances, some patients have only one functioning lung with another pulmonary artery seriously hypoplastic or atretic. For theses patients, completion of a Fontan operation will be challenging. We reported a 17-year-old girl with a single ventricle and heterotaxy syndrome and only her left lung functioning, who underwent one-lung Fontan operation with a satisfactory result. PMID:27713611

  17. Hypoplastic left heart syndrome: a review

    PubMed Central

    Roberts, Gobergs; Elza, Salputra; Ingūna, Lubaua

    2016-01-01

    Background. Hypoplastic left heart syndrome (HLHS) is an etiologically multifactorial congenital heart disease affecting one in 5,000 newborns. Thirty years ago there were no treatment options for this pathology and the natural course of the disease led to death, usually within the first weeks of life. Recently surgical palliative techniques have been developed allowing for a five-year survival in more than half the cases. Materials and methods. We reviewed literature available on HLHS, specifically its anatomy, embryology and pathophysiology, and treatment. The Pubmed and ClinicalKey databases were searched using the key words hypoplastic left heart syndrome, foetal aortic valvuloplasty, foetal septoplasty, Norwood procedure, bidirectional Glenn procedure, Fontan procedure, hybrid procedure. The relevant literature was reviewed and included in the article. We reported a case from Children’s Clinical University Hospital, Riga, to illustrate treatment tactics in Latvia. Results. There are three possible directions for therapy in newborns with HLHS: orthotopic heart transplantation, staged surgical palliation and palliative non-surgical treatment or comfort care. Another treatment mode – foetal therapy – has arisen. Staged palliation and full Fontan circulation is a temporary solution, however, the only means for survival until heart transplantation. Fifty to 70% of patients who have gone through all three stages of palliation live to the age of five years. Conclusions. The superior mode of treatment is not yet clear and the management must be based on each individual case, the experience of each clinic, as well as the financial aspects and will of the patient’s parents. PMID:28356795

  18. Pure midbrain ischemia and hypoplastic vertebrobasilar circulation.

    PubMed

    Gilberti, Nicola; Gamba, Massimo; Costa, Angelo; Vergani, Veronica; Spezi, Raffaella; Pezzini, Alessandro; Volonghi, Irene; Mardighian, Dikran; Gasparotti, Roberto; Padovani, Alessandro; Magoni, Mauro

    2014-02-01

    Isolated midbrain infarction is rare and little is known about etiology and patient's long-term follow up. We aimed to describe the clinical features, the causative diseases and the outcome of patients with isolated midbrain infarction who were admitted to our center, focusing on vascular abnormalities of posterior circulation. All patients with first acute ischemic stroke limited to the midbrain were included and their demographic features, neurological symptoms, neuroimaging data, and cardiovascular risk factors were recorded. Functional outcome, using modified Rankin scale, was assessed at discharge and at the 3 month follow up evaluation. We found nine patients with acute isolated midbrain infarction, representing 0.61 % of all ischemic stroke admitted to our center. The most common cause of stroke was small-vessel disease (88.8 %). At stroke onset, none of the patients had consciousness disturbances, and four patients (44.4 %) had gait impairment, five patients (55.5 %) presented with diplopia due to involvement of the third nerve or fascicular type of third-nerve palsy, seven patients (77.7 %) had vascular anomalies of vertebrobasilar circulation: the most frequent was vertebral artery hypoplasia [four patients (44.4 %)]. At follow up evaluation, seven patients (77.7 %) had a good functional outcome and no patients experienced recurrence of cerebrovascular events. As isolated midbrain infarction is uncommon, specific ocular motor signs, mainly third-nerve palsy, may help to identify and localize the mesencephalic infarct. Abnormalities in vertebrobasilar circulation, such as hypoplastic basilar or vertebral artery, are frequently associated with isolated midbrain ischemia. The hypoplastic vertebrobasilar system may predispose to posterior ischemic stroke.

  19. [Hypoplastic left heart syndrome (general review)].

    PubMed

    Tláskal, T; Povýsilová, V; Vondrys, D; Skovránek, J

    1999-05-01

    The hypoplastic left heart syndrome (HLHS) is a critical congenital heart lesion with a small left ventricle in combination with stenosis or atresia of the aortic and the mitral valve. This heart disease is associated with a nearly 100% mortality at neonatal age. Until recently, this heart lesion was considered inoperable because of extremely unfavourable morphology. Introduction of the Norwood three-step reconstructive operation on one hand, and heart transplantation in neonates, on the other hand, improved the prognosis of patients with this complex heart lesion. In our country, however, this heart disease, if found during the first months of pregnancy, represents an indication for its termination, and neonates with HLHS are offered only symptomatic medical treatment. On basis of good experience from several most experienced cardiac centres we believe that it is necessary to reassess the statement considering HLHS as an inoperable disease. The main change from this aspect necessitates, however, a detailed analysis of the whole problem not only from the morphological, clinical and surgical point of view but also from philosophical, psychological, socio-economic and health care organisation aspects.

  20. Fetal and neonatal imaging and strategy of primary neonatal heart transplantation in hypoplastic left heart with Ebstein's anomaly.

    PubMed

    Hammel, James M; Danford, David A; Spicer, Robert L; Kutty, Shelby

    2015-03-01

    We present the anatomic constellation of mitral stenosis/aortic atresia variant of hypoplastic left heart syndrome, Ebstein's anomaly, and partial anomalous pulmonary venous return, an exceeding rare congenital heart defect. Prenatal echocardiography led to concern about the capacity of the right ventricle to increase cardiac output with lung expansion and pulmonary arterial runoff at birth, prompting the precaution of extracorporeal membrane oxygenator standby at delivery. Stage I palliation was not attempted, and control of pulmonary arterial blood flow was achieved with pulmonary artery banding, allowing sufficient ongoing hemodynamic stability. Orthotopic cardiac transplantation, repair of hypoplastic aortic arch, and primary sutureless repair of left pulmonary veins was performed, using dual-site arterial cannulation and continuous mild hypothermic cardiopulmonary bypass. We discuss how this unique echocardiographic anatomy influenced the surgical decision and point out how it guided therapy toward a strategy of primary transplantation rather than standard staged surgical palliation.

  1. Hypoplastic area method for analyzing dental enamel hypoplasia.

    PubMed

    Ensor, B E; Irish, J D

    1995-12-01

    Most analyses of dental enamel hypoplasia compare frequencies of disturbed tooth types, which do not account for variability in the area of affected enamel. An alternate methodology, hypoplastic area, is presented here that accounts for this variability by combining acute and continuous enamel hypoplasia into an interval-level variable. The method compares samples based on individuals, by multiple tooth type variables, or by a single value rather than by tooth types. Use of the hypoplastic area method is illustrated by analyzing human skeletal dentitions in three archaeological samples: Meroitic Nubians from Semna South, Sudan; Anasazi from Navajo Reservoir, New Mexico; and Mogollon from Grasshopper Pueblo, Arizona. Both univariate and multivariate statistical tests are employed to assess variation in defects between individuals and samples. By incorporating measurements of continuous defects, the hypoplastic area method provides information beyond that of frequency data in comparing levels of stress. Flexibility of the method is also discussed.

  2. Local Fetal Lung Renin-Angiotensin System as a Target to Treat Congenital Diaphragmatic Hernia

    PubMed Central

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge

    2012-01-01

    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT1) and type 2 (AT2) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT1 receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT2-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT2 receptor is presented as a putative antenatal therapy for CDH. PMID:22113494

  3. Local fetal lung renin-angiotensin system as a target to treat congenital diaphragmatic hernia.

    PubMed

    Nogueira-Silva, Cristina; Carvalho-Dias, Emanuel; Piairo, Paulina; Nunes, Susana; Baptista, Maria J; Moura, Rute S; Correia-Pinto, Jorge

    2012-03-27

    Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT₁) and type 2 (AT₂) receptors of angiotensin II (ANGII) was assessed by immunohisto-chemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular pathway alterations assessed by Western blot. In nitrofen-induced CDH model, pregnant rats were treated with saline or PD-123319. In pups, lung growth, protein/DNA ratio, radial saccular count, epithelial differentiation and lung maturation, vascular morphometry, right ventricular hypertrophy and overload molecular markers, gasometry and survival time were evaluated. Results demonstrated that all RAS components were constitutively expressed in the lung during gestation and that ANGII had a stimulatory effect on lung branching, mediated by AT₁ receptor, through p44/42 and Akt phosphorylation. This stimulatory effect on lung growth was mimicked by AT₂-antagonist (PD-123319) treatment. In vivo antenatal PD-123319 treatment increased lung growth, ameliorated indirect parameters of pulmonary hypertension, improved lung function and survival time in nonventilated CDH pups, without maternal or fetal deleterious effects. Therefore, this study demonstrated a local and physiologically active RAS during lung morphogenesis. Moreover, selective inhibition of AT₂ receptor is presented as a putative antenatal therapy for CDH.

  4. [Considerations in orthodontic bracket adhesion to hypoplastic and hypomineralized enamel].

    PubMed

    Sapir, S

    2007-01-01

    Developmental defects of enamel are frequently observed in the pediatric and orthodontic dental clinic. Proper diagnosis may improve the clinician's dental care. The importance of prevention is emphasized as well as the proper management of adhesion of orthodontic brackets to hypoplastic and hypominerilized enamel. A review of recent research findings in this field is discussed as well as recommendations for clinical management of some common dental defects: hypoplasia, diffuse and demarcated opacities, and amelogenesis imperfecta.

  5. The myocardial and coronary histopathology and pathogenesis of hypoplastic left heart syndrome.

    PubMed

    Cole, Charles R; Eghtesady, Pirooz

    2016-01-01

    Hypoplastic left heart syndrome has the greatest mortality rate among all CHDs and without palliation is uniformly fatal. Despite noble efforts, the aetiology of this syndrome is unknown and a cure remains elusive. The genetic and anatomic heterogeneity of hypoplastic left heart syndrome supports a rethinking of old hypotheses and warrants further investigation into the histological and vascular variations recognised with this syndrome. In an effort to elucidate the pathogenesis of hypoplastic left heart syndrome, this review will focus on its unique myocardial and coronary pathology as well as evaluate the association of hypoplastic left heart syndrome with the endocardial fibroelastosis reaction.

  6. Methylenetetrahydrofolate Reductase C677T: Hypoplastic Left Heart and Thrombosis.

    PubMed

    Spronk, Kimberly J; Olivero, Anthony D; Haw, Marcus P; Vettukattil, Joseph J

    2015-10-01

    The incidence of congenital heart defects is higher in infants with mutation of methylenetetrahydrofolate reductase (MTHFR) gene. The MTHFR C677T gene decreases the bioavailability of folate and increases plasma homocysteine, a risk factor for thrombosis. There have been no reported cases in the literature on the clinical implications of this procoagulable state in the setting of cyanotic heart disease, which itself has prothrombotic predisposition. Two patients with hypoplastic left heart syndrome developed postoperative thrombotic complications, both were homozygous for MTHFR C677T. We present these cases and highlight the implications of MTHFR mutation in the management of complex congenital heart disease. © The Author(s) 2015.

  7. Hypoplastic left heart syndrome: palliation without cardiopulmonary bypass.

    PubMed

    Tucker, W Y; McKone, R C; Weesner, K M; Kon, N D

    1990-05-01

    Our 100% mortality rate with first-stage palliation of hypoplastic left heart syndrome performed with cardiopulmonary bypass led us to a procedure not necessitating bypass. In nine neonates with this congenital heart defect, a woven Dacron graft was placed from the main pulmonary artery to the descending thoracic aorta. The patent ductus arteriosus was ligated and the main pulmonary artery banded distal to the graft and proximal to the bifurcation. Five patients were extubated within 4 days. Only low-dose inotropic support was required in eight of the nine. There were no bleeding problems. Four patients died in the hospital: one of Candida sepsis at 81 days, one of low cardiac output at 2 days, and two of restrictive atrial septal defect at 3 and 5 days. The five living patients were discharged 11 to 80 days postoperatively (mean 38 days). We now perform balloon septostomies preoperatively in all patients and believe that this will improve the survival rate. We believe this simpler approach to the treatment of hypoplastic left heart syndrome may allow survival for a cardiac transplant or a staged Fontan procedure at a later date for more definitive treatment.

  8. Posterior circulation ischemia in patients with fetal-type circle of Willis and hypoplastic vertebrobasilar system.

    PubMed

    Lochner, Piergiorgio; Golaszewski, Stefan; Caleri, Francesca; Ladurner, Gunther; Tezzon, Frediano; Zuccoli, Giulio; Nardone, Raffaele

    2011-12-01

    Little attention has been given to the fetal-type posterior circle of Willis (FTP) in the literature; also symptomatic basilar artery (BA) hypoplasia has been rarely reported. We aimed to illustrate that the association of a hypoplastic vertebrobasilar system (VBS) with the FTP may lead to posterior circulation ischemia. Magnetic resonance imaging and three-dimensional time-of-flight magnetic resonance angiography were performed in 88 consecutive patients with ischemic stroke or TIA in the VBS. Thirteen patients were identified with either stroke or TIA in the context of a hypoplastic VBS and a fetal origin of the posterior cerebral arteries. All patients had unilateral or bilateral FTP, hypoplastic BA and at least one hypoplastic vertebral artery. Transcranial color-coded duplex revealed decreased flow velocity and increased pulsatility index along the BA. A hypoplastic VBS may be accompanied by the FTP and its simultaneous occurrence can predispose to ischemic events in the posterior circulation.

  9. Hypoplastic uterus and clitoris enlargement in Swyer syndrome.

    PubMed

    Hétu, Valérie; Caron, Evelyne; Francoeur, Diane

    2010-02-01

    Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads. Copyright 2010 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  10. [Urethroplasty in hypoplastic-dysplastic corpus spongiosum and short urethra].

    PubMed

    Vitarelli, Antonio; Divenuto, Lucia; Altomare, Mauro; Masiello, Giuseppe; Pagliarulo, Arcangelo

    2013-01-01

    Congenital penile curvature and chordee are a rare malformative condition most frequently associated with hypospadias, but varying degrees of penile curvature are observed with an orthotopic meatus. Disease becomes evident after puberty, when curvature becomes more apparent with erection. We present a case of a young man (16 years old), with ventral congenital penile curvature without hypospadias and with hypoplastic-dysplastic corpus spongiosum and short urethra, who could not have normal sexual intercourses. The patient underwent first-stage urethroplasty with urethral opening and graft of buccal mucosa and creation of a temporary hypospadic meatus. No post-operative complications were observed. There were no residual penile curvatures. Results are promising and satisfactory after the first surgical stage and provide a solid ground for the final reconstruction.

  11. Structure, Integrity, and Function of the Hypoplastic Corpus Callosum in Spina Bifida Myelomeningocele

    PubMed Central

    Crawley, Jennifer T.; Hasan, Khader; Hannay, H. Julia; Dennis, Maureen; Jockell, Catherine

    2014-01-01

    Abstract Although there are many studies of people with complete or partial hypogenesis of the corpus callosum (CC), little is understood about the hypoplastic CC in which all structures are present but thinned. Spina bifida myelomeningocele (SBM) is a model organism for such studies because many have either a hypogenetic or hypoplastic CC. We used diffusion tensor tractography (DTT) to evaluate the hypoplastic CC in SBM and its relation to interhemispheric functions and intelligence quotient (IQ). Participants were individuals with SBM and an intact or hypoplastic CC (n=28), who were compared to a typically developing comparison group (n=32). Total and regional DTT volume and integrity measures (fractional anisotropy, axial diffusivity, and radial diffusivity) of the CC were related to measures of intelligence (IQ), bimanual motor functioning, and dichotic auditory performance. As predicted, DTT showed variations in volume and integrity that were maximized in the entire CC and the posterior CC. IQ correlated with entire CC volume, anterior and posterior regional CC volumes, and also with measures of integrity. Bimanual motor functioning correlated with the anterior and posterior volumes of the CC but not with any integrity measures. Axial diffusivity in the posterior CC was negatively correlated with right ear dichotic listening performance. The hypoplastic CC is not macrostructurally or microstructurally intact in SBM, even when it appears radiologically intact. Both volume and integrity of the posterior regions were related to reductions in IQ and to interhemispheric processing. These findings may transfer to other disorders characterized by a hypoplastic CC. PMID:25014561

  12. A cluster of hypoplastic left heart malformation in Baltimore, Maryland.

    PubMed

    Kuehl, K S; Loffredo, C A

    2006-01-01

    Congenital cardiovascular malformations (CCVMs) of the left side of the heart show familial recurrence of various forms of obstructive malformations, including hypoplastic left heart (HLH), interrupted aortic arch, coarctation of the aorta, and aortic stenosis. In a previous population-based study in the Baltimore-Washington region, these malformations were associated with parental reports of occupational or leisure solvent exposure, overt diabetes, and family history of CCVM in first-degree relatives. Spatial analysis in this well-characterized study population may augment self-reported data by revealing additional associations with potential environmental risk factors. We used spatial analysis to identify clusters of HLH as a group. The study population included all live-born cases of hypoplastic left heart syndrome diagnosed in the first year of life between 1981 and 1989 and a random sample of unaffected infant controls matched by year and hospital of birth. The nested case-control cohort in this spatial analysis included 77 HLH cases and 1894 controls in Maryland and the District of Columbia. Nonparametric and regression analyses included personal variables from the interview data set as well as spatial variables. A region of Baltimore was identified that contained HLH at twice the expected frequency based on the distribution of population younger than 5 years of age. The region included 30 of 77 geocoded cases of HLH in the cohort and is significant by spatial scanning at p = 0.056. Within this region, male cases of HLH were disproportionately present compared to females. This cluster is in a region of Baltimore with industrial release of solvents, dioxin, and polychlorinated biphenyls in air. Outside the cluster, HLH is associated with family history of CCVM in a first-degree relative, maternal exposure to miscellaneous solvents, paternal anesthesia, maternal art painting, aspirin ingestion, and maternal diabetes. Inside the cluster, father's painting and

  13. Acetanilide oxidation in phenylbutazone-associated hypoplastic anaemia.

    PubMed

    Cunningham, J L; Leyland, M J; Delamore, I W; Evans, D A

    1974-08-03

    Acetanilide like phenylbutazone is paraoxidized by the liver endoplasmic reticulum as a primary biotransformation step. Both compounds were given at different times to each of 10 healthy volunteer subjects and the plasma disappearances measured. Correlation was shown between plasma clearance values of the two compounds (r = + 0.7067; P < 0.05).Eight patients with hypoplastic anaemia after phenylbutazone therapy were investigated. Plasma clearance values and half lives of acetanilide were measured in this group of patients and compared with those of a group of 30 healthy volunteer controls. There was a significant decrease in clearance (P < 0.01) and lengthening of half lives (P < 0.001 in the patients with phenylbutazone-associated hypoplasia. Five patients with idiopathic aplastic anaemia-that is, without history of antecedent phenylbutazone ingestion-were similarly investigated with acetanilide and there was no significant difference between the results in these patients and those in the control group.It is suggested that relatively poor paraoxidation of phenylbutazone producing high blood concentrations on a given dose may be a factor responsible for the drug-associated hypoplasia even though it does not explain the similar pattern of adverse reactions reported in association with oral administration of the metabolite oxyphenbutazone.

  14. Mining temporal data sets: hypoplastic left heart syndrome case study

    NASA Astrophysics Data System (ADS)

    Kusiak, Andrew; Caldarone, Christopher A.; Kelleher, Michael D.; Lamb, Fred S.; Persoon, Thomas J.; Gan, Yuan; Burns, Alex

    2003-03-01

    Hypoplastic left heart syndrome (HLHS) affects infants and is uniformly fatal without surgery. Post-surgery mortality rates are highly variable and dependent on postoperative management. The high mortality after the first stage surgery usually occurs within the first few days after procedure. Typically, the deaths are attributed to the unstable balance between the pulmonary and systemic circulations. An experienced team of physicians, nurses, and therapists is required to successfully manage the infant. However, even the most experienced teams report significant mortality due to the extremely complex relationships among physiologic parameters in a given patient. A data acquisition system was developed for the simultaneous collection of 73 physiologic, laboratory, and nurse-assessed variables. Data records were created at intervals of 30 seconds. An expert-validated wellness score was computed for each data record. A training data set consisting of over 5000 data records from multiple patients was collected. Preliminary results demonstratd that the knowledge discovery approach was over 94.57% accurate in predicting the "wellness score" of an infant. The discovered knowledge can improve care of complex patients by development of an intelligent simulator that can be used to support decisions.

  15. Survival of Children With Hypoplastic Left Heart Syndrome

    PubMed Central

    Siffel, Csaba; Riehle-Colarusso, Tiffany; Oster, Matthew E.; Correa, Adolfo

    2015-01-01

    OBJECTIVE To examine the survival of infants with hypoplastic left heart syndrome (HLHS) and potential influence of demographic and clinical characteristics on survival using population-based data. METHODS Infants with nonsyndromic HLHS (n = 212) born between 1979 and 2005 were identified through the Metropolitan Atlanta Congenital Defects Program. Vital status was ascertained through 2009 based on linkage with vital records. We estimated Kaplan-Meier survival probabilities stratified by select demographic and clinical characteristics. RESULTS The overall survival probability to 2009 was 24% and significantly improved over time: from 0% in 1979–1984 to 42% in 1999–2005. Survival probability was 66% during the first week, 27% during the first year of life, and 24% during the first 10 years. Survival of very low and low birth weight or preterm infants and those born in high-poverty neighborhoods was significantly poorer. For children with information on surgical intervention (n = 88), the overall survival was 52%, and preterm infants had significantly poorer survival (31%) compared with term infants (56%). For children who survived to 1 year of age, long-term survival was ~90%. CONCLUSIONS Survival to adolescence of children with nonsyndromic HLHS born in metropolitan Atlanta has significantly improved in recent years, with those born full term, with normal birth weight, or in a low-poverty neighborhood having a higher survival probability. Survival beyond infancy to adolescence is high. A better understanding of the growing population of survivors with HLHS is needed to inform resource planning. PMID:26391936

  16. Hypoplastic left heart syndrome: current considerations and expectations.

    PubMed

    Feinstein, Jeffrey A; Benson, D Woodrow; Dubin, Anne M; Cohen, Meryl S; Maxey, Dawn M; Mahle, William T; Pahl, Elfriede; Villafañe, Juan; Bhatt, Ami B; Peng, Lynn F; Johnson, Beth Ann; Marsden, Alison L; Daniels, Curt J; Rudd, Nancy A; Caldarone, Christopher A; Mussatto, Kathleen A; Morales, David L; Ivy, D Dunbar; Gaynor, J William; Tweddell, James S; Deal, Barbara J; Furck, Anke K; Rosenthal, Geoffrey L; Ohye, Richard G; Ghanayem, Nancy S; Cheatham, John P; Tworetzky, Wayne; Martin, Gerard R

    2012-01-03

    In the recent era, no congenital heart defect has undergone a more dramatic change in diagnostic approach, management, and outcomes than hypoplastic left heart syndrome (HLHS). During this time, survival to the age of 5 years (including Fontan) has ranged from 50% to 69%, but current expectations are that 70% of newborns born today with HLHS may reach adulthood. Although the 3-stage treatment approach to HLHS is now well founded, there is significant variation among centers. In this white paper, we present the current state of the art in our understanding and treatment of HLHS during the stages of care: 1) pre-Stage I: fetal and neonatal assessment and management; 2) Stage I: perioperative care, interstage monitoring, and management strategies; 3) Stage II: surgeries; 4) Stage III: Fontan surgery; and 5) long-term follow-up. Issues surrounding the genetics of HLHS, developmental outcomes, and quality of life are addressed in addition to the many other considerations for caring for this group of complex patients.

  17. Preoperative trophic feeds in neonates with hypoplastic left heart syndrome.

    PubMed

    Toms, Rune; Jackson, Kimberly W; Dabal, Robert J; Reebals, Cristina H; Alten, Jeffrey A

    2015-01-01

    The aim of this is study is to determine if preoperative trophic feeds (TFs) can improve outcomes after Norwood palliation. This is a retrospective cohort study. The setting is a pediatric cardiovascular intensive care unit in a tertiary hospital. The patients were 50 consecutive patients with hypoplastic left heart, excluding 5 patients with prematurity or other significant comorbidities. Thirty-one patients that received preoperative TFs (20-30 mL/kg) were compared with 14 that remained nothing by mouth. Decision to initiate feeds was based on attending preference. All patients had protocolized feeds postoperatively, with initiation via transpyloric tube when patient was on minimal inotropes. Demographic, feeding, and other clinical outcome data were collected retrospectively from the patient medical record. There were no differences in demographics or preoperative risk factors (mechanical ventilation and lowest pH) between the two groups. Overall survival to discharge was 78% (25/31 TF, 10/14 nothing by mouth, P = .7). Neonates receiving TFs had less fluid administration in the cardiovascular operating room (P = .002), a more negative 48-hour postoperative fluid balance (P = .03), and median 3 days shorter duration of mechanical ventilation (P = .006). Trophic feeds patients also had a nonsignificant trend toward lower peak lactic acid (P = .06), lower inotropic score (P = .15), shorter hospital length of stay (P = .19), and faster time to tolerance of full enteral and oral feeds by 3 and 8 days, respectively (P = .06 and .01). There were no episodes of necrotizing enterocolitis in either group. Preoperative TFs before Norwood palliation appear safe and are associated with shorter duration of mechanical ventilation, a trend toward more stable postoperative hemodynamics, less fluid overload, and earlier postoperative feeding tolerance. © 2014 Wiley Periodicals, Inc.

  18. Modeling Outcomes: Modified Aortic Arch Advancement for Neonatal Hypoplastic Arch.

    PubMed

    Nellis, Joseph R; Chung, Timothy K; Agarwal, Nandita; Torres, Jose E; Holgren, Sarah E; Raghavan, Madhavan L; Turek, Joseph W

    Numerous surgical approaches regarding aortic arch advancement for neonatal arch hypoplasia have been described. These repairs can be classified into two categories: those that incorporate a patch and those that do not. The decision between repairs remains largely experiential, rather than empirical, because of the limited number of reported outcomes. We report early outcomes from neonates undergoing modified aortic arch advancement with an anterior patch and our experience using computational fluid dynamic modeling to better understand the hemodynamic consequences associated with this repair. A retrospective review of neonates undergoing aortic arch advancement with anterior patch in 2014 at a single institution was performed. Anatomical, perioperative, and follow-up data were collected. Three-dimensional cardiac magnetic resonance images were used to generate computational fluid dynamic models of the modified anterior patch and direct end-to-side repairs. Cardiac waveform inputs were simulated and hemodynamic analyzed. Ten neonates underwent modified aortic arch advancement. No hemodynamically significant gradients were observed at a median follow-up of 0.77 (0.30-1.2) years. Asymmetrical flow was observed in the end-to-side repair, whereas more concentric laminar flow was observed throughout the modified model. Spatial variations in velocities immediately distal to the anastomosis were greater in the end-to-side model (0.35 vs 0.17 m/s, P < 0.001). Time-averaged variations in wall shear stress during systole were greater in the end-to-side model at the same location (3.44 vs 1.98 dynes/cm, P < 0.001). Early outcomes after the use of an anterior patch for neonatal hypoplastic aortic arch repair show favorable hemodynamic outcomes.

  19. Microtensile bond strength to enamel affected by hypoplastic amelogenesis imperfecta.

    PubMed

    Yaman, Batu Can; Ozer, Fusun; Cabukusta, Cigdem Sozen; Eren, Meltem M; Koray, Fatma; Blatz, Markus B

    2014-02-01

    This study compared the microtensile bond strengths (μTBS) of two different self-etching (SE) and etchand- rinse (ER) adhesive systems to enamel affected by hypoplastic amelogenesis imperfecta (HPAI) and analyzed the enamel etching patterns created by the two adhesive systems using scanning electron microscopy (SEM). Sixteen extracted HPAI-affected molars were used for the bond strength tests and 2 molars were examined under SEM for etching patterns. The control groups consisted of 12 healthy third molars for μTBS tests and two molars for SEM. Mesial and distal surfaces of the teeth were slightly ground flat. The adhesive systems and composite resin were applied to the flat enamel surfaces according to the manufacturers' instructions. The tooth slabs containing composite resin material on their mesial and distal surfaces were cut in the mesio-distal direction with a slow-speed diamond saw. The slabs were cut again to obtain square, 1-mm-thick sticks. Finally, each stick was divided into halves and placed in the μTBS tester. Bond strength tests were performed at a speed of 0.5 mm/min. Data were analyzed with two-way ANOVA and Tukey's tests. There was no significant difference between the bond strength values of ER and SE adhesives (p > 0.05). However, significant differences were found between HPAI and control groups (p < 0.05). HPAI-affected enamel surfaces exhibited mild intra- and inter-prismatic enamel etching patterns after orthophosphoric acid application, while conditioning of HPAI-affected enamel with SE primer created a slightly rough and grooved surface. SE and ER adhesive systems provide similar bond strengths to HPAI-affected enamel surfaces.

  20. [The study on chemical composition and crystalline structure of hypoplastic primary dental enamel].

    PubMed

    Zheng, S; Deng, H; Gao, X

    1997-11-01

    The present study, firstly, analyzed chemical composition of hypoplastic primary teeth by electron probe analyzer and compared the hypoplastic part with the normal part in the same tooth; secondly, by X-ray diffraction analyzer, studied the hypoplastic dental enamel and the normal dental enamel, and compared the crystalline structure between different dental enamel and with that of the hydroxyapatite. The aim was to find out any change of crystalline structure. Two exfoliated hypoplastic deciduous anterior teeth were used for the electron probe study. The normal part of each tooth served as control. Determinations of weight percentage (wt%) were made for P, Al, Mg, Ca, Mn, Fe, Zn, Sr, Na, K and F. Four exfoliated hypoplastic deciduous anterior teeth and eight exfoliated normal deciduous anterior teeth were used for the X-ray diffraction study. We found by X-ray diffraction that the length of the alpha-axis of enamel crystallite and the distance of lattice plane (corresponding 300) were increased in defective enamel and could be associated with the increased content of magnesium detected by electron probe. Thus, the present study demonstrated that there were both quantity and quality changes in the enamel hypoplasia lesion, which may increase the susceptibility of the defective teeth to caries.

  1. New developments in the treatment of hypoplastic left heart syndrome.

    PubMed

    Maher, K O; Gidding, S S; Baffa, J M; Pizarro, C; Norwood, W I

    2004-02-01

    Hypoplastic left heart syndrome (HLHS) was once a uniformly fatal disease, accounting the majority of neonatal deaths due to congenital heart defects. Twenty-five years of advances in the surgical and medical management of this disease have resulted in dramatic improvements in survival for these children. The goal for patients with HLHS should be survival of near 100% with a good quality of life. The advances described in this manuscript detail some of the new techniques used in the surgical and medical management. For infants undergoing staged reconstruction, the Norwood procedure is performed in the newborn period, followed by a hemi-Fontan operation at 6 months of age, and a modified Fontan operation at 1 to 2 years of age. A significant recent modification of the Norwood procedure is the placement of a right ventricle to pulmonary artery (RV-PA) conduit instead of a systemic artery to pulmonary shunt (modified Blalock-Taussig or BT shunt) as the source of pulmonary blood flow. Our recent experience with this modification demonstrated an incremental increase in survival, improved postoperative stability, and decreased inter-stage mortality. At catheterization, significant differences in hemodynamic parameters were present that were consistent with improved coronary blood flow, decreased volume load to the single right ventricle, and improved pulmonary artery growth in those patients with the RV-PA conduit. The 3rd stage in the surgical treatment of HLHS is the modified Fontan operation or cavo-pulmonary anastamosis. A new approach for Fontan completion is the placement of a stent covered with a thin layer of Goretex from the inferior vena cava to the hemi-Fontan baffle. This can be performed in the catheterization laboratory, with a decrease in post-procedure pleural effusions, lower mortality, and a shorter length of stay. The future of treatment for HLHS may eventually involve a single open-heart procedure with initial and final interventions being performed

  2. Leftward displacement of septum primum in hypoplastic left heart syndrome.

    PubMed

    Park, Matthew V; Fedderly, Raymond T; Frommelt, Peter C; Frommelt, Michele A; Pelech, Andrew N; Jaquiss, Robert D B; Mussatto, Kathleen; Tweddell, James S

    2013-04-01

    Embryologic development of atrial septum primum antedates formation of the atrioventricular and semilunar valves. Leftward displacement of the superior attachment of septum primum (LDSP) has only been described in hypoplastic left heart syndrome (HLHS). This study reports the frequency of LDSP in HLHS and correlates LDSP with other echocardiographic features of HLHS. Preoperative echocardiograms for 72 consecutive patients with classic HLHS from 1996 to 2002 at Children's Hospital of Wisconsin were reviewed. One patient was excluded for inadequate imaging. Data for the 71 patients included the following: size, location, and Doppler gradient across the atrial septal defect (ASD); location of attachment of septum primum; size and patency of the aortic valve (AoV) annulus; size and patency of the mitral valve (MV) annulus; ascending aorta diameter (AAD); and left-ventricular end diastolic dimension (LVEDD). Patients were categorized into three groups: aortic atresia/mitral atresia (AA/MA), aortic atresia/mitral stenosis (AA/MS), and aortic stenosis/mitral stenosis (AS/MS). LDSP was seen in 46 of 71 patients (64 %). By diagnostic group, 32 of 35 patients with AA/MA had LDSP (91 %) compared with 10 of 19 AA/MS patients (53 %) and 4 of 17 AS/MS patients (24 %), p < 0.05. AoV patency was seen in 4 of 46 (9 %) patients with LDSP compared with 13 of 25 (52 %) patients with normal atrial attachment, p < 0.005. Mean left heart dimensions in infants with LDSP compared with normal attachment were as follows: AoV annulus 2.24 versus 3.83 mm, AAD 2.34 versus 4.1 mm, MV annulus 3.21 versus 6.48 mm, and LVEDD 6.38 versus 13.83 mm. By two-way analysis of variance of diagnostic category versus atrial septal attachment with interaction, MV annulus and AAD were independently predicted smaller by LDSP versus normal atrial attachment, p < 0.05. Nonsignificant factors included AoV annulus, LVEDD, ASD size, and Doppler gradient. LDSP correlates with more severe maldevelopment of the left

  3. Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

    PubMed

    Thompson, Sophie M; Connell, Marilyn G; van Kuppevelt, Toin H; Xu, Ruoyan; Turnbull, Jeremy E; Losty, Paul D; Fernig, David G; Jesudason, Edwin C

    2011-06-14

    Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional

  4. Structure and epitope distribution of heparan sulfate is disrupted in experimental lung hypoplasia: a glycobiological epigenetic cause for malformation?

    PubMed Central

    2011-01-01

    Background Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. Results The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme. We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. Conclusions The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by

  5. [Severe hypoplastic left heart syndrome: palliative care after prenatal diagnosis].

    PubMed

    Noseda, C; Mialet-Marty, T; Basquin, A; Letourneur, I; Bertorello, I; Charlot, F; Le Bouar, G; Bétrémieux, P

    2012-04-01

    We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for prenatal diagnosis. The information given to parents at the moment of choice is capital for them to make their own decision: in our team the real choice for parents stands between termination of pregnancy (TOP) and palliative care (PC). The Norwood procedure is rarely proposed to parents in France and it is performed in very few centers. Heart transplant is never proposed nor done at this age. The objectives of our study were to understand the reasons for the choice of PC, take stock of our experience of PC, and relate the benefits but also the disadvantages of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others wanted to live their pregnancy and meet their child at birth, therefore requesting neonatal PC. No family asked for the Norwood procedure. Four children died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1 child was operated on for coarctation of the aorta (unknown before birth) and is still alive 1.5 years later. Maternal motivations to continue the pregnancy were clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case, negative experiences of previous abortions in the second case. In another case, the parents hesitated between PC and Norwood surgery. For the other women, the reasons were less clearly expressed. In our series, HLHS is the first indication for PC from prenatal diagnosis (7/16 cases in the same period) while in the literature, heart diseases are the second cause of TOP after the neurological causes. The overrepresentation of this pathology in the families who opt for PC may be due to the unconscious image that both professionals and families have of HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no suffering. Our study may change this view: a child was in fact carrying a

  6. Neurodevelopment and quality of life for children with hypoplastic left heart syndrome: current knowns and unknowns

    PubMed Central

    Goldberg, Caren S.; Mussatto, Kathleen; Licht, Daniel; Wernovsky, Gil

    2013-01-01

    The aim of this review is to describe the current state of knowledge related to neurodevelopmental outcomes and quality of life for children with hypoplastic left heart syndrome and to explore future questions to be answered for this group of children. PMID:22152534

  7. Shearing flows of a dry granular material - hypoplastic constitutive theory and numerical simulations

    NASA Astrophysics Data System (ADS)

    Fang, Chung; Wang, Yongqi; Hutter, Kolumban

    2006-12-01

    In the present study, the Goodman-Cowin theory is extended to incorporate plastic features to construct an elasto-visco-plastic constitutive model for flowing dry granular materials. A thermodynamic analysis, based on the Müller-Liu entropy principle, is performed to derive the equilibrium expressions of the constitutive variables. Non-equilibrium responses are proposed by use of a quasi-linear theory, in particular a hypoplastic-type relation is introduced to model the internal friction and plastic effects. It is illustrated that the Goodman-Cowin theory can appropriately be extended to include frictional effects into the evolution equation of the volume fraction (i.e. the so-called balance of equilibrated force) and the equilibrium expression of the Cauchy stress tensor. The implemented model is applied to investigate conventional steady isothermal granular flows with incompressible grains, namely simple plane shear, inclined gravity-driven and vertical channel-flows, respectively. Numerical results show that the hypoplastic effect plays a significant role in the behaviour of a flowing granular material. The obtained profiles of the velocity and the volume fraction with hypoplastic features are usually sharper and the shear-thinning effect is more significant than that without such plastic effects. This points at the possible wide applicability of the present model in the fields of granular materials and soil mechanics. In addition, the present paper also provides a framework for a possible extension of the hypoplastic theories which can be further undertaken. Copyright

  8. Hypoplastic left heart syndrome with restrictive atrial septum and advanced heart block documented with a novel fetal electrocardiographic monitor

    PubMed Central

    NARAYAN, H. K.; FIFER, W.; CARROLL, S.; KERN, J.; SILVER, E.; WILLIAMS, I. A.

    2012-01-01

    Hypoplastic left ventricle with congenital heart block has been reported previously in a fetus with concurrent left atrial isomerism and levo-transposition of the great arteries. We present the unusual case of an infant diagnosed in utero with hypoplastic left heart syndrome, a restrictive atrial septum and advanced heart block but with D-looping of the ventricles and no atrial isomerism. In addition, fetal heart rhythm was documented with the assistance of a new fetal electrocardiographic monitor. PMID:21374749

  9. Feeding Protocols for Neonates With Hypoplastic Left Heart Syndrome: A Review.

    PubMed

    Jenkins, Erin

    2015-01-01

    Optimizing nutrition in neonates with hypoplastic left heart syndrome is essential, given the high rate of growth failure in this population. Infants with hypoplastic left heart syndrome are predisposed to nutritional deficiency as a result of their increased metabolic demand; however, early enteral feeding also increases the risk of serious gastrointestinal morbidity and mortality caused by poor intestinal perfusion. Consequently, providers have difficulty deciding when and how to safely feed these patients. A review of the literature found that implementation of a structured enteral feeding protocol may decrease the risk of gastrointestinal complications while also minimizing dependence on parenteral nutrition and decreasing length of hospital stay. As these studies were limited, further research is warranted to establish a best practice feeding protocol to decrease risk and optimize nutrition in this fragile population.

  10. Isolated hypoplastic circumflex coronary artery: a rare cause of haemorrhagic myocardial infarction in a young athlete.

    PubMed

    Riede, Florian-Nikolaus; Bulla, Stefan; Grundmann, Sebastian; Werner, Martin; Riede, Urs-Nikolaus; Otto, Claudia

    2013-06-06

    Hypoplastic coronary artery disease is a rare condition that may lead to myocardial infarction and sudden death. Here we describe for the first time an isolated hypoplasia of the left circumflex artery (LCX). An otherwise healthy and athletically active 16-year-old boy was admitted to the intensive care unit (ICU) after out-of-hospital cardiac arrest. He died 12 hours after the initial event. Autopsy revealed an isolated hypoplastic LCX and acute haemorrhagic infarction in the posterolateral myocardium. The existence of isolated hypoplasia of the LCX challenges our understanding of coronary artery development. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1558483061962648.

  11. Isolated hypoplastic circumflex coronary artery: a rare cause of haemorrhagic myocardial infarction in a young athlete

    PubMed Central

    2013-01-01

    Hypoplastic coronary artery disease is a rare condition that may lead to myocardial infarction and sudden death. Here we describe for the first time an isolated hypoplasia of the left circumflex artery (LCX). An otherwise healthy and athletically active 16-year-old boy was admitted to the intensive care unit (ICU) after out-of-hospital cardiac arrest. He died 12 hours after the initial event. Autopsy revealed an isolated hypoplastic LCX and acute haemorrhagic infarction in the posterolateral myocardium. The existence of isolated hypoplasia of the LCX challenges our understanding of coronary artery development. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1558483061962648 PMID:23742172

  12. A rare combination of vascular anomalies: Hypoplastic aortic arch, coarctation of the aorta and poststenotic aneurysm.

    PubMed

    Bayar, Nermin; Arslan, Şakir; Üreyen, Çağın Mustafa; Küçükseymen, Selçuk; Erol, Bekir

    2015-04-01

    Coarctation of the aorta is the fifth most common congenital cardiac anomaly encountered in adults. It is important for prognosis to diagnose and treat this anomaly early. An aneurysm might develop due to tunica media abnormalities in patients with coarctation of the aorta. We hereby present an adult case with a very rare combination of vascular anomalies including ascending aorta aneurysm, hypoplastic aortic arch, coarctation of the aorta and poststenotic aneurysm.

  13. Novel ENAM and LAMB3 mutations in Chinese families with hypoplastic amelogenesis imperfecta.

    PubMed

    Wang, Xin; Zhao, Yuming; Yang, Yuan; Qin, Man

    2015-01-01

    Amelogenesis imperfecta is a group of inherited diseases affecting the quality and quantity of dental enamel. To date, mutations in more than ten genes have been associated with non-syndromic amelogenesis imperfecta (AI). Among these, ENAM and LAMB3 mutations are known to be parts of the etiology of hypoplastic AI in human cases. When both alleles of LAMB3 are defective, it could cause junctional epidermolysis bullosa (JEB), while with only one mutant allele in the C-terminus of LAMB3, it could result in severe hypoplastic AI without skin fragility. We enrolled three Chinese families with hypoplastic autosomal-dominant AI. Despite the diagnosis falling into the same type, the characteristics of their enamel hypoplasia were different. Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. Disease-causing mutations were identified and perfectly segregated with the enamel defects in three families: a 19-bp insertion mutation in the exon 7 of ENAM (c.406_407insTCAAAAAAGCCGACCACAA, p.K136Ifs*16) in Family 1, a single-base deletion mutation in the exon 5 of ENAM (c. 139delA, p. M47Cfs*11) in Family 2, and a LAMB3 nonsense mutation in the last exon (c.3466C>T, p.Q1156X) in Family 3. Our results suggest that heterozygous mutations in ENAM and LAMB3 genes can cause hypoplastic AI with markedly different phenotypes in Chinese patients. And these findings extend the mutation spectrum of both genes and can be used for mutation screening of AI in the Chinese population.

  14. Development of an echocardiographic scoring system to predict biventricular repair in neonatal hypoplastic left heart complex.

    PubMed

    Mart, Christopher Robin; Eckhauser, Aaron Wesley

    2014-12-01

    Neonates born with borderline left heart hypoplasia, or hypoplastic left heart complex, can undergo biventricular repair while those with severe left heart hypoplasia require single ventricle palliation. Deciding which patients are candidates for biventricular repair may be very difficult since there are no scoring systems to predict biventricular repair in these patients. The purpose of this study is to develop an echocardiographic scoring system capable of predicting successful biventricular repair in neonatal hypoplastic left heart complex. The study cohort consisted of twenty consecutive neonates with hypoplastic left heart complex presenting between 9/2008 and 5/2013. Multiple retrospective echocardiographic measurements of the right and left heart were performed. Six patients with significant LH hypoplasia (patent mitral and aortic valves, small left ventricle) who had undergone single ventricle repair were used to validate the scoring system. Seventeen patients underwent biventricular repair and three underwent single ventricle repair. A scoring system (2V-Score) was developed using the equation {[(MV4C/AVPSLA) ÷ (LV4C/RV4C)] + MPA}/BSA. Using a cutoff value of ≤ 16.2, a biventricular repair would have been predicted with a sensitivity of 1.0, specificity 1.0, positive predictive value 1.0, negative predictive value 1.0, area under the ROC curve 1.0, and the p value was 0.0004. The 2V-Score was more accurate than the Rhodes, CHSS, or Discriminant scores in retrospectively predicting biventricular repair in this cohort. The 2V-Score shows promise in being able to predict a successful biventricular repair in patients with hypoplastic left heart complex but requires prospective validation prior to widespread clinical application.

  15. Neonatal bronchial reconstruction after Norwood procedure for hypoplastic left heart syndrome.

    PubMed

    Gaughan, Colleen B; Nguyen, Dao; Ricci, Marco

    2009-03-01

    Left bronchial obstruction is a rare complication after neonatal aortic arch reconstruction. This article describes the surgical management of a neonate with hypoplastic left heart syndrome who underwent a stage 1 Norwood reconstruction. A mediastinal infection developed with an abscess that caused left bronchial obstruction and disruption. The left bronchus was repaired successfully by using a pedicle intercostal muscle flap that was used to cover the defect.

  16. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males.

    PubMed

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi

    2011-04-01

    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  17. Heart failure due to "disappearing" aortic valve in hypoplastic left heart syndrome.

    PubMed

    Loftus, Patrick D; Erickson, Lance K; Everitt, Melanie D; Kaza, Aditya K

    2014-04-01

    We present the unusual case of a "disappearing" aortic valve in an infant with hypoplastic left heart syndrome (mitral and aortic stenosis) that underwent Norwood palliation at birth and subsequently a Glenn operation. Angiographic images at the time of operation showed no apparent insufficiency of the native aortic valve. Over the course of 14 months following operation, the patient developed significant cardiomegaly with a workup revealing severe native aortic valve insufficiency. Following orthotopic heart transplantation, examination of the explanted heart revealed a complete absence of native aortic valve leaflets.

  18. A fetus with hypoplastic left heart syndrome and tricuspid stenosis with evolving hydrops fetalis.

    PubMed

    Divanović, Allison; Witte, David; Michelfelder, Erik

    2012-10-01

    Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect that results in death if not treated shortly after birth. In approximately 60 to 70% of cases, HLHS can be detected prenatally and generally is well tolerated due to the presence of the foramen ovale and ductus arteriosus, which allow for blood to bypass the left side of the heart but still provide adequate blood flow to the systemic circulation. A rare case of HLHS involving a fetus with tricuspid valve stenosis, abnormal venous Doppler findings, and hydrops is reported.

  19. Scintigraphy in evaluation of the hypoplastic right hepatic lobe: a rare variant.

    PubMed Central

    Suneja, S. K.; Teal, J. S.

    1989-01-01

    A rare variant of right hepatic lobe hypoplasia associated with high gallbladder position in the right upper abdomen is described. Pain is frequent and may be due to cholelithiasis. It is important to recognize this variant because an associated hypertrophic left hepatic lobe can clinically masquerade as an abdominal mass. Radionuclide studies and abdominal computerized tomography are useful in defining the hypertrophied left hepatic lobe and ectopic gallbladder. The duodenum and hepatic flexure are positioned high due to space left by the hypoplastic right lobe. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2733056

  20. Thermodynamically consistent modeling of granular-fluid mixtures incorporating pore pressure evolution and hypoplastic behavior

    NASA Astrophysics Data System (ADS)

    Heß, Julian; Wang, Yongqi; Hutter, Kolumban

    2017-01-01

    This paper presents a new, thermodynamically consistent model for granular-fluid mixtures, derived with the entropy principle of Müller and Liu. Including a pressure diffusion equation combined with the concept of extra pore pressure, and hypoplastic material behavior, thermodynamic restrictions are imposed on the constitutive quantities. The model is applied to a granular-fluid flow, using a closing assumption in conjunction with the fluid pressure. While the focal point of the work is the conceptional part, i.e. the thermodynamic consistent modeling, numerical simulations with physically reasonable results for simple shear flow are also carried out.

  1. Berlin Heart ventricular assist device in a child with hypoplastic left heart syndrome.

    PubMed

    Chu, Michael W A; Sharma, Kapil; Tchervenkov, Christo I; Jutras, Luc F; Lavoie, Josée; Shemie, Sam D; Laliberte, Eric; Calaritis, Christos; Cecere, Renzo

    2007-03-01

    We report the implantation of a Berlin Heart ventricular assist device (VAD) in a 4-year-old boy with hypoplastic left heart syndrome previously palliated with Norwood and Glenn operations, who presented with progressive ventricular failure and hypoxemia. Insertion of a 30-mL pneumatic pediatric pump with cannulation of the systemic right ventricle and aorta had a salutary effect on cardiac output, improving oxygen saturations. While awaiting heart transplantation, multiple thromboembolic complications developed and he died, despite therapeutic heparinization and aspirin therapy. Important lessons learned about VAD support in Glenn physiology, anticoagulation, and complications of the Berlin Heart are discussed.

  2. Biventricular Badness: Rare Images of Ebstein Anomaly of the Tricuspid Valve in a Patient with Hypoplastic Left Heart Syndrome.

    PubMed

    Werho, David K; Thorsson, Thor; Owens, Sonal T; Fifer, Carlen

    2015-08-01

    We report a rare case of hypoplastic left heart syndrome coexisting in a patient with Ebstein anomaly of the tricuspid valve, which has previously been described only in pathological studies. A fetal echocardiogram at 27-weeks gestation showed severe aortic stenosis with evolving hypoplastic left heart syndrome, significant endocardial fibroelastosis, a dysplastic tricuspid valve with moderate regurgitation, right atrial and ventricular dilation, and signs of fetal congestive heart failure. Due to inadequate left heart size, the patient was not a candidate for fetal intervention for critical aortic stenosis, and repeat studies showed progression of the lesion through the pregnancy. The infant was delivered at 36-weeks gestation with signs of hydrops, and a postnatal echocardiogram confirmed hypoplastic left heart syndrome as well as severe Ebstein anomaly of the tricuspid valve. The infant did not survive to intervention.

  3. Children with hypoplastic left heart syndrome have lower quality of life than healthy controls and children with other illnesses.

    PubMed

    Dempster, Nicole; Cua, Clifford L; Wernovsky, Gil; Caris, Elizabeth; Neely, Trent; Allen, Robin; Butz, Catherine

    2017-08-29

    Previous studies suggest that children with congenital cardiac diagnoses report lower quality of life when compared with healthy norms. A few studies have evaluated quality of life specifically in children born with hypoplastic left heart syndrome, a condition requiring several surgeries before age three. The aim of this study was to use an empirically validated and standardised measure - the Pediatric Quality of Life Inventory - to evaluate quality of life in children with hypoplastic left heart syndrome and compare the findings with similar, medically complicated samples. The parent-report Pediatric Quality of Life Inventory was administered, and demographic information was collected through an internet portal. A total of 121 caregivers of children with hypoplastic left heart syndrome responded. The sample included children aged 2-18 years (M=10.81 years). Independent sample t-tests were used to compare our sample with published norms of healthy children and children with acute or chronic illnesses. Children with hypoplastic left heart syndrome were rated as having significantly lower overall quality-of-life scores (M=59.69) compared with published norms of children without medical diagnoses (M=83.00) and those with acute (M=78.70) or chronic (M=77.19) illnesses (p<0.001). Children with hypoplastic left heart syndrome complicated by a stroke or seizure (15%) reported the lowest quality of life. The results held for all subscales (p<0.001). Children with hypoplastic left heart syndrome appear to be a significantly vulnerable population with difficulties in functioning across psychosocial domains and across the age span. Further research is required to facilitate early identification of the need for resources for these children and families, especially for children who experience additional medical complications.

  4. Double-outlet right ventricle with an intact interventricular septum and concurrent hypoplastic left ventricle in a calf.

    PubMed

    Newhard, D K; Jung, S W; Winter, R L; Kuca, T; Bayne, J; Passler, T

    2017-01-19

    A 3-day-old Hereford heifer calf presented for evaluation of lethargy and dyspnea, with persistent hypoxia despite supplemental oxygen therapy. A grade III/VI right apical systolic murmur was noted during cardiac auscultation. Echocardiography revealed a double-outlet right ventricle with an intact interventricular septum and concurrent hypoplastic left ventricle and tricuspid valve dysplasia. Post-mortem examination revealed additional congenital anomalies of ductus arteriosus, patent foramen ovale, and persistent left cranial vena cava. This report illustrates the use of echocardiographic images to diagnose a double-outlet right ventricle with an intact interventricular septum and a hypoplastic left ventricle in a calf.

  5. Recessive Mutations in ACPT, Encoding Testicular Acid Phosphatase, Cause Hypoplastic Amelogenesis Imperfecta.

    PubMed

    Seymen, Figen; Kim, Youn Jung; Lee, Ye Ji; Kang, Jenny; Kim, Tak-Heun; Choi, Hwajung; Koruyucu, Mine; Kasimoglu, Yelda; Tuna, Elif Bahar; Gencay, Koray; Shin, Teo Jeon; Hyun, Hong-Keun; Kim, Young-Jae; Lee, Sang-Hoon; Lee, Zang Hee; Zhang, Hong; Hu, Jan C-C; Simmer, James P; Cho, Eui-Sic; Kim, Jung-Wook

    2016-11-03

    Amelogenesis imperfecta (AI) is a heterogeneous group of genetic disorders affecting tooth enamel. The affected enamel can be hypoplastic and/or hypomineralized. In this study, we identified ACPT (testicular acid phosphatase) biallelic mutations causing non-syndromic, generalized hypoplastic autosomal-recessive amelogenesis imperfecta (AI) in individuals from six apparently unrelated Turkish families. Families 1, 4, and 5 were affected by the homozygous ACPT mutation c.713C>T (p.Ser238Leu), family 2 by the homozygous ACPT mutation c.331C>T (p.Arg111Cys), family 3 by the homozygous ACPT mutation c.226C>T (p.Arg76Cys), and family 6 by the compound heterozygous ACPT mutations c.382G>C (p.Ala128Pro) and 397G>A (p.Glu133Lys). Analysis of the ACPT crystal structure suggests that these mutations damaged the activity of ACPT by altering the sizes and charges of key amino acid side chains, limiting accessibility of the catalytic core, and interfering with homodimerization. Immunohistochemical analysis confirmed localization of ACPT in secretory-stage ameloblasts. The study results provide evidence for the crucial function of ACPT during amelogenesis.

  6. Electrolytically detachable coils for closure of a modified baffle fenestration in patients with hypoplastic left heart syndrome (HLHS).

    PubMed

    Gundel, Florian; Liebig, Thomas; Eicken, Andreas; Sebening, Walter; Hess, John

    2009-06-26

    Today total cavopulmonary connection (TCPC) is the treatment of choice for long term palliation of patients with hypoplastic left heart syndrome (HLHS). We report a new, relatively simple and effective method to occlude a modified baffle (TCPC) fenestration via the left hepatic vein in two patients with HLHS with the use of electrolytically detachable platinum microcoils after a failed tourniquet closure.

  7. A second case of contractures, webbed neck, micrognathia, hypoplastic nipples, and distinctive facial features: confirmation of the Dinno syndrome.

    PubMed

    Wall, Nerilee; McGaughran, Julie

    2012-04-01

    We report on a child with micrognathia, a short, webbed neck, joint contractures, hypoplastic nipples, and a number of other anomalies. There are striking similarities to a patient reported by [Dinno and Weisskopf (1976); Synd Ident, 4:10-12], and we postulate that this child represents the second patient with this condition.

  8. Modeling the ski-snow contact in skiing turns using a hypoplastic vs an elastic force-penetration relation.

    PubMed

    Mössner, M; Heinrich, D; Schindelwig, K; Kaps, P; Schretter, H; Nachbauer, W

    2014-06-01

    A ski-snow interaction model is presented. The force between ski and snow is decomposed into a penetration force normal to the snow surface, a shear force parallel to it, and friction. The purpose of this study was to investigate the benefits of a hypoplastic vs an elastic contact for penetration in the simulation of skiing turns. To reduce the number of influencing factors, a sledge equipped with skis was considered. A forward dynamic simulation model for the sledge was implemented. For the evaluation of both contact models, the deviation between simulated trajectories and experimental track data was computed for turns of 67 and 42 m. Maximum deviations for these turns were 0.44 and 0.14 m for the hypoplastic contact, and 0.6 and 7.5 m for the elastic contact, respectively. In the hypoplastic contact, the penetration depth of the ski's afterbody maintained nearly the same value as the part under maximum load, whereas it decreased in the elastic contact. Because the shear force is proportional to the penetration depth, the hypoplastic contact resulted in a higher shearing resistance. By replacing the sledge with a skier model, one may investigate more complex skier actions, skiing performance, or accident-prone skiing maneuvers.

  9. Does left ventricular size impact on intrinsic right ventricular function in hypoplastic left heart syndrome?

    PubMed

    Schlangen, Jana; Fischer, Gunther; Steendijk, Paul; Petko, Colin; Scheewe, Jens; Hart, Christopher; Hansen, Jan H; Ahrend, Frederick; Rickers, Carsten; Kramer, Hans-Heiner; Uebing, Anselm

    2013-08-20

    The size of the remnant left ventricle (LV) may influence right ventricular function and thus long-term outcome in palliated hypoplastic left heart syndrome (HLHS). We therefore sought to assess the impact of the size of the hypoplastic LV on intrinsic RV function in HLHS patients after Fontan surgery. Fifty-seven HLHS patients were studied 2.5 (range: 0.8-12.6) years after Fontan-type palliation with the pressure-volume conductance system. The patient cohort was divided into two groups according to the median LV area index (group 1: LV area index ≤ 1.33 cm(2)/m(2), n=29; group 2: LV area index>1.33 cm(2)/m(2), n=28). The slopes of the end systolic elastance (Ees) and the preload recruitable stroke work relation (Mw) were not different between group 1 and 2 (Ees: 2.70 ± 1.92 vs. 3.68 ± 2.68 mmHg/ml; Mw: 52.75 ± 14.98 vs. 51.09 ± 16.63 mmHg x ml; P=NS for all). Furthermore, the systolic responses to dobutamine were not statistically different between groups. However, the slope of the end diastolic stiffness (Eed) was higher in group 2 and catecholaminergic stimulation resulted in a decrease in Eed in group 2 (group 1: 0.40 ± 0.26 vs. 0.52 ± 0.45; group 2: 0.68 ± 0.44 vs. 0.47 ± 0.38 mmHg/ml, P<0.01). Furthermore Eed was lowest in patients with mitral atresia/aortic atresia, the anatomic subgroup with the smallest LV remnant. Intrinsic systolic RV function is not affected by the size of the hypoplastic LV in survivors of surgical palliation of HLHS. Diastolic stiffness, however, was higher in patients with a larger LV remnant. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Disturbed myocardial connexin 43 and N-cadherin expressions in hypoplastic left heart syndrome and borderline left ventricle.

    PubMed

    Mahtab, Edris A F; Gittenberger-de Groot, Adriana C; Vicente-Steijn, Rebecca; Lie-Venema, Heleen; Rijlaarsdam, Marry E B; Hazekamp, Mark G; Bartelings, Margot M

    2012-12-01

    Borderline left ventricle is the left ventricular morphology at the favorable end of the hypoplastic left heart syndrome. In contrast to the severe end, it is suitable for biventricular repair. Wondering whether it is possible to identify cases suitable for biventricular repair from a developmental viewpoint, we investigated the myocardial histology of borderline and severely hypoplastic left ventricles. Postmortem specimens of neonatal, unoperated human hearts with severe hypoplastic left heart syndrome and borderline left ventricle were compared with normal specimens and hearts from patients with transposition of the great arteries. After tissue sampling of the lateral walls of both ventricles, immunohistochemical and immunofluorescence stainings against cardiac troponin I, N-cadherin, and connexin 43, important for proper cardiac differentiation, were done. All severely hypoplastic left hearts (7/7) and most borderline left ventricle hearts (4/6) showed reduced sarcomeric expressions of troponin I in left and right ventricles. N-cadherin and connexin 43 expressions were reduced in intercalated disks. The remaining borderline left ventricle hearts (2/6) were histologically closer to control hearts. Four of 6 borderline left ventricle hearts showed myocardial histopathology similar to the severely hypoplastic left hearts. The remainder were similar to normal hearts. Our results and knowledge regarding the role of epicardial-derived cells in myocardial differentiation lead us to postulate that an abnormal epicardial-myocardial interaction could explain the observed histopathology. Defining the histopathologic severity with preoperative myocardial biopsy samples of hearts with borderline left ventricle might provide a diagnostic tool for preoperative decision making. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  11. Hypoplastic myelodysplastic syndrome transformed in acute myeloid leukemia after androgens and cyclosporin. A treatment.

    PubMed

    Gologan, R; Ostroveanu, Daniela; Dobrea, Camelia; Gioadă, Liliana

    2003-01-01

    The apparent contradiction between clonal expansion and marrow failure encountered in myelodysplastic syndromes (MDS) is more evident in hypocellular forms at presentation. Hypoplastic MDS (hMDS) appears to be a distinct clinicopathologic entity, accounting for about 15% from all MDS. The pathogeny is supposed to result from immunosupressive mechanisms and some observations on successful treatment with Cyclosporine A (CsA) are reported. The case of a young female patient diagnosed by bone marrow core biopsy with hMDS - refractory anemia (FAB and WHO classification) with normal karyotype and scarce CD34(+) cells by immunohistophenotyping is presented. She was treated with androgens followed by CsA for a few months and shortly after she developed an acute myeloid leukemia (M4) which responded to low-doses of daily oral melphalan. This is one of the first few reports on such an event during the immunosuppressive therapy in MDS and the possible explanations for this unusual evolution are discussed.

  12. Hypoplastic left heart syndrome: from comfort care to long-term survival

    PubMed Central

    Yabrodi, Mouhammad; Mastropietro, Christopher W.

    2017-01-01

    The management of hypoplastic left heart syndrome (HLHS) has changed substantially over the past four decades. In the 1970s, children with HLHS could only be provided with supportive care. As a result, most of these unfortunate children died within the neonatal period. The advent of the Norwood procedure in the early 1980s has changed the prognosis for these children, and the majority now undergoing a series of three surgical stages that can support survival beyond the neonatal period and into early adulthood. This review will focus on the Norwood procedure and the other important innovations of the last half century that have improved our outlook toward children born with HLHS. PMID:27701379

  13. Hypoplastic left heart syndrome – a review of supportive percutaneous treatment

    PubMed Central

    Moszura, Tomasz; Dryżek, Paweł

    2014-01-01

    Due to the complex anatomical and haemodynamic consequences of hypoplastic left heart syndrome (HLHS), patients with the condition require multistage surgical and supportive interventional treatment. Percutaneous interventions may be required between each stage of surgical palliation, sometimes simultaneously with surgery as hybrid interventions, or after completion of multistage treatment. Recent advances in the field of interventional cardiology, including new devices and techniques, have significantly contributed to improving results of multistage HLHS palliation. Knowledge of the potential interventional options as well as the limitation of percutaneous interventions will enable the creation of safe and effective treatment protocols in this highly challenging group of patients. In this comprehensive review we discuss the types, goals, and potential complications of transcatheter interventions in patients with HLHS. PMID:25489307

  14. Feasibility and safety of biventricular repair in neonates with hypoplastic left heart complex.

    PubMed

    Bergonzini, S; Mendoza, A; Paz, M A; Garcia, E; Aguilar, J M; Arlati, F G; Galletti, L; Comas, J V

    2015-02-01

    Hypoplastic left heart syndrome is a spectrum of structural cardiac malformations characterized by variable underdevelopment of the left heart-aorta complex. A minority of patients having a milder degree of left ventricular hypoplasia, described as hypoplastic left heart complex (HLHC), may be selected for biventricular repair. The objective of this study was to assess the outcome of the biventricular approach in HLHC. We evaluated retrospectively 30 neonates diagnosed with HLHC from the "12 de Octubre" University Hospital, following established criteria. We analyzed the echocardiographic data recorded just after birth and at last follow-up after surgery. All patients were operated on in the neonatal period using various surgical techniques. There were no early deaths and only 1 late death after a mean follow-up of 62.9 ± 43.8 months. All patients presented a significant growth of the left ventricular structures, with a Z-score increase of 1.17 ± 1.05 for mitral annulus, 1.72 ± 1.23 for aortic annulus, and 1.33 ± 1.46 for left ventricular end-diastolic diameter. Postoperatively, 18 patients showed a left valvular stenosis, and 17 patients underwent a reoperation and/or an interventional procedure. Freedom from surgery or interventional catheterizations at 1, 3 and 5 years was 53, 49 and 43%, respectively. The 29 current survivors are all in a good functional status. In our experience, we achieved good results from biventricular repair in patients with HLHC, with a significant growth of left heart structures and an excellent clinical status at a medium-term follow-up. Nevertheless, there was a high rate of reoperations and/or interventional catheterizations.

  15. Mutations in the Hepatocyte Nuclear Factor-1β Gene Are Associated with Familial Hypoplastic Glomerulocystic Kidney Disease

    PubMed Central

    Bingham, Coralie; Bulman, Michael P.; Ellard, Sian; Allen, Lisa I. S.; Lipkin, Graham W.; Hoff, William G. van't; Woolf, Adrian S.; Rizzoni, Gianfranco; Novelli, Giuseppe; Nicholls, Anthony J.; Hattersley, Andrew T.

    2001-01-01

    Familial glomerulocystic kidney disease (GCKD) is a dominantly inherited condition characterized by glomerular cysts and variable renal size and function; the molecular genetic etiology is unknown. Mutations in the gene encoding hepatocyte nuclear factor (HNF)–1β have been associated with early-onset diabetes and nondiabetic renal disease—particularly renal cystic disease. We investigated a possible role for the HNF-1β gene in four unrelated GCKD families and identified mutations in two families: a nonsense mutation in exon 1 (E101X) and a frameshift mutation in exon 2 (P159fsdelT). The family members with HNF-1β gene mutations had hypoplastic GCKD and early-onset diabetes or impaired glucose tolerance. We conclude that there is genetic heterogeneity in familial GCKD and that the hypoplastic subtype is a part of the clinical spectrum of the renal cysts and diabetes syndrome that is associated with HNF-1β mutations. PMID:11085914

  16. Numerical simulation of soil creep with a visco-hypoplastic constitutive model

    NASA Astrophysics Data System (ADS)

    Wang, Shun; Wu, Wei

    2016-04-01

    Slow-moving landslides make up a great part of geohazards in the Three Gorges reservoir (TGR) in China. Most of them move at speed of several centimeters per year (or even less) and show evidence of creep behaviour. It has been suggested that motion of creep landslides is mainly governed by the viscous properties of sheared materials forming the rupture zone, as these zones are where most of the slope deformation localizes. Understanding of creep behaviour of slipping material calls for laboratory tests as well as advanced constitutive models. For this purpose, a high order visco-hypoplastic constitutive model has been introduced. Unlike some of the visco-hypoplasric models, which consider the total strain rate as a combination of reversible strain rate and viscous strain rate respectively, such as dot{bm{e}}=dot{bm{e}}^e+dot{bm{e}}vis (where dot{bm{e}}, dot{bm{e}}e and dot{bm{e}}vis are the total strain rate ,reversible strain rate and viscous strain rate respectively), the proposed visco-hypolastic constitutive model decompose the Cauchy stress into a statical part and a dynamical part, bm{s}=hat{bm{s}}+\\check{bm{s}} (where bm{s},hat{bm{s}} and \\check{bm{s}} are total stress ,statical stress and dynamical stress respectively), whereas the strain rate has been considered as a whole. Within in this framework, stress change induced by strain acceleration can be taken into account. Moreover, compared with some special creep models, which may only valid for one or two stages of the three-state creep, i.e. primary creep, secondary creep and tertiary creep, this novel scheme is able to describe creep test with the whole three stages. This model has been also implemented into FEM code to evaluate some boundary-value problems. An explicit adaptive Rung-Kutta-Fehlberg algorithm is applied for stress-point integration. For verification of this model, numerical triaxial tests compared with laboratory tests have been conducted. Then a homogenous slope has been taken as an

  17. Extra-anatomical bypass in complex and recurrent aortic coarctation and hypoplastic arch.

    PubMed

    Delmo Walter, Eva Maria; Javier, Mariano Francisco Del Maria; Hetzer, Roland

    2017-09-01

    Our goal was to report the selection schemes, technical variations and long-term outcome of extra-anatomical bypass to correct complex, recurrent aortic coarctation and hypoplastic aortic arch. Between 1989 and 2012, 53 patients (mean age 13.2 ± 4.3, median 11.6, range 9-23 years) with complex aortic coarctation (n = 33; long-segment hypoplastic aortic arch in 15), recurrent coarctation (n = 20; anastomosic pseudoaneurysm in 10), underwent correction using extra-anatomical bypass, either with (n = 18: femoral bypass = 13, left heart bypass = 5) or without (n = 35) extracorporeal circulation via a left lateral thoracotomy (n= 48) and combined median sternotomy and median laparotomy (n = 5). The decision to use extracorporeal circulation was based on the anatomical location of the coarctation, the length of the hypoplasia and a history of previous repair. Preoperatively, mean systolic blood pressure was 130 ± 30 mmHg at rest and 180 ± 40 mmHg during exercise, with a mean pressure gradient of 80 ± 11.6 (range 40-120) mmHg. Various extra-anatomical bypass strategies included left subclavian artery to descending aorta (n = 38), ascending aorta to left subclavian artery (n = 3), ascending aorta to descending aorta (n = 4), aortic arch to descending aorta (n = 3) and ascending aorta to abdominal aorta (n = 5). Graft size (median 18, range 10-26, mm) was chosen according to the diameter of the vessel proximal and distal to the planned graft. No operative deaths, paraplegia or abdominal malperfusion occurred. The mean reduction in systolic blood pressure was 60 ± 25 mmHg without pressure gradients. During a mean follow-up of 18.3 ± 3.7 years, there were no reoperations, graft complications or pseudoaneurysm formation on anastomotic sites. Seven (11.6%) patients are on antihypertensive medications. No patient presented with claudication nor did anyone experience orthostatic problems from

  18. Surgical management of a neonate with congenitally corrected transposition of the great vessels, hypoplastic right aortic arch, and Ebstein anomaly.

    PubMed

    Filippelli, Sergio; Perri, Gianluigi; Kirk, Richard; Hasan, Asif; Griselli, Massimo

    2013-11-01

    We report a neonate with a primary diagnosis of congenitally corrected transposition (ccTGA) of the great vessels, hypoplastic right aortic arch, and a severely regurgitant Ebstein tricuspid valve (TV). During the fetal period, she was listed for heart transplantation, and two weeks after birth due to a deterioration of her general condition, we performed a Norwood-Sano modified procedure. After 58 days a donor heart became available and the baby successfully received a orthotopic heart transplantation.

  19. Effects of milk flow on the physiological and behavioural responses to feeding in an infant with hypoplastic left heart syndrome.

    PubMed

    Pados, Britt F; Thoyre, Suzanne M; Estrem, Hayley H; Park, Jinhee; Knafl, George J; Nix, Brant

    2017-01-01

    Infants with hypoplastic left heart syndrome often experience difficulty with oral feeding, which contributes to growth failure, morbidity, and mortality. In response to feeding difficulty, clinicians often change the bottle nipple, and thus milk flow rate. Slow-flow nipples have been found to reduce the stress of feeding in other fragile infants, but no research has evaluated the responses of infants with hypoplastic left heart syndrome to alterations in milk flow. The purpose of this study was to evaluate the physiological and behavioural responses of an infant with hypoplastic left heart syndrome to bottle feeding with either a slow-flow (Dr. Brown's Preemie) or a standard-flow (Dr. Brown's Level 2) nipple. A single infant was studied for three feedings: two slow-flow and one standard-flow. Oral feeding, whether with a slow-flow or a standard-flow nipple, was distressing for this infant. During slow-flow feeding, she experienced more coughing events, whereas during standard-flow she experienced more gagging. Disengagement and compelling disorganisation were most common during feeding 3, that is slow-flow, which occurred 2 days after surgical placement of a gastrostomy tube. Clinically significant changes in heart rate, oxygen saturation, and respiratory rate were seen during all feedings. Heart rate was higher during standard-flow and respiratory rate was higher during slow-flow. Further research is needed to examine the responses of infants with hypoplastic left heart syndrome to oral feeding and to identify strategies that will support these fragile infants as they learn to feed. Future research should evaluate an even slower-flow nipple along with additional supportive feeding strategies.

  20. Early restenosis following biodegradable stent implantation in an aortopulmonary collateral of a patient with pulmonary atresia and hypoplastic pulmonary arteries.

    PubMed

    McMahon, Colin J; Oslizlok, Paul; Walsh, Kevin P

    2007-04-01

    Traditionally, the implantation of stents in young children with small blood vessels has been avoided as the presence of a metallic or fixed stent structure limits the ability to further dilate the stent with vessel growth. Pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries represents one such cohort where the placement of fixed nondegradable stents has been difficult. We report a 2-month-old girl with pulmonary atresia, VSD, and multiple aorto-pulmonary collaterals with severely hypoplastic pulmonary arteries who underwent placement of a biodegradable magnesium stent within a stenotic aorto-pulmonary collateral. Although there was an initial significant increase in vessel diameter, significant restenosis occurred 4 months after stent placement. This to our knowledge represents the first case of the use of biodegradable stents in a child with severely hypoplastic pulmonary arteries. Although further refinements in stent technology are required, this development will hopefully usher in a new era of potential intervention in children previously deemed unsuitable for stent placement.

  1. A Novel Mutation of the HNF1B Gene Associated With Hypoplastic Glomerulocystic Kidney Disease and Neonatal Renal Failure

    PubMed Central

    Alvelos, Maria Inês; Rodrigues, Magda; Lobo, Luísa; Medeira, Ana; Sousa, Ana Berta; Simão, Carla; Lemos, Manuel Carlos

    2015-01-01

    Abstract Hepatocyte nuclear factor 1 beta (HNF1B) plays an important role in embryonic development, namely in the kidney, pancreas, liver, genital tract, and gut. Heterozygous germline mutations of HNF1B are associated with the renal cysts and diabetes syndrome (RCAD). Affected individuals may present a variety of renal developmental abnormalities and/or maturity-onset diabetes of the young (MODY). A Portuguese 19-month-old male infant was evaluated due to hypoplastic glomerulocystic kidney disease and renal dysfunction diagnosed in the neonatal period that progressed to stage 5 chronic renal disease during the first year of life. His mother was diagnosed with a solitary hypoplastic microcystic left kidney at age 20, with stage 2 chronic renal disease established at age 35, and presented bicornuate uterus, pancreatic atrophy, and gestational diabetes. DNA sequence analysis of HNF1B revealed a novel germline frameshift insertion (c.110_111insC or c.110dupC) in both the child and the mother. A review of the literature revealed a total of 106 different HNF1B mutations, in 236 mutation-positive families, comprising gross deletions (34%), missense mutations (31%), frameshift deletions or insertions (15%), nonsense mutations (11%), and splice-site mutations (8%). The study of this family with an unusual presentation of hypoplastic glomerulocystic kidney disease with neonatal renal dysfunction identified a previously unreported mutation of the HNF1B gene, thereby expanding the spectrum of known mutations associated with renal developmental disorders. PMID:25700310

  2. Surgery for infants with a hypoplastic systemic ventricle and severe outflow obstruction: early results with a modified Norwood procedure.

    PubMed Central

    Bu'Lock, F. A.; Stümper, O.; Jagtap, R.; Silove, E. D.; De Giovanni, J. V.; Wright, J. G.; Sethia, B.; Brawn, W. J.

    1995-01-01

    OBJECTIVE--Prospective audit of the first year of implementation of a modified approach to palliation for infants with hypoplastic systemic ventricle and severe systemic outflow obstruction. SETTING--Tertiary referral centre for neonatal and infant cardiac surgery. PATIENTS AND METHODS--17 of 19 infants (aged < 35 days) presenting to Birmingham Children's Hospital in 1993 with hypoplastic systemic ventricle and severe outflow obstruction underwent surgery. This was performed using a new modification of the Norwood-type arch repair, without the use of exogenous material, and a 3.5 mm Gore-tex shunt between the innominate and right pulmonary arteries. The Gore-tex shunt was replaced by a cavopulmonary shunt between 3 and 5 months later. Clinical, morphological, and functional determinants of outcome were examined. RESULTS--10 (59%) infants survived initial surgery. All proceeded to cavopulmonary shunt without further loss. Significant atrioventricular valve regurgitation seemed to be the main risk factor for poor outcome. If this was excluded, the morphology of the dominant ventricle seemed to have little effect on the outcome of initial surgery. CONCLUSIONS--Early survival was achieved in 59% of patients in the first year of implementation of a protocol for surgery in infants with hypoplastic systemic ventricle and severe outflow obstruction. The construction of a neoaorta without the use of exogenous material may allow improved later growth of the neoaorta. Early cavopulmonary shunt can be performed safely and should reduce mid-term complications from cyanosis and systemic ventricular volume loading. PMID:7540406

  3. Interstage Home Monitoring After Newborn First-Stage Palliation for Hypoplastic Left Heart Syndrome: Family Education Strategies.

    PubMed

    Nieves, Jo Ann; Uzark, Karen; Rudd, Nancy A; Strawn, Jennifer; Schmelzer, Anne; Dobrolet, Nancy

    2017-04-01

    Children born with hypoplastic left heart syndrome are at high risk for serious morbidity, growth failure, and mortality during the interstage period, which is the time from discharge home after first-stage hypoplastic left heart syndrome palliation until the second-stage surgical intervention. The single-ventricle circulatory physiology is complex, fragile, and potentially unstable. Multicenter initiatives have been successfully implemented to improve outcomes and optimize growth and survival during the interstage period. A crucial focus of care is the comprehensive family training in the use of home surveillance monitoring of oxygen saturation, enteral intake, weight, and the early recognition of "red flag" symptoms indicating potential cardiopulmonary or nutritional decompensation. Beginning with admission to the intensive care unit of the newborn with hypoplastic left heart syndrome, nurses provide critical care and education to prepare the family for interstage home care. This article presents detailed nursing guidelines for educating families on the home care of their medically fragile infant with single-ventricle circulation. ©2017 American Association of Critical-Care Nurses.

  4. A nationwide survey of hypoplastic myelodysplastic syndrome (a multicenter retrospective study).

    PubMed

    Kobayashi, Takashi; Nannya, Yasuhito; Ichikawa, Motoshi; Oritani, Kenji; Kanakura, Yuzuru; Tomita, Akihiro; Kiyoi, Hitoshi; Kobune, Masayoshi; Kato, Junji; Kawabata, Hiroshi; Shindo, Motohiro; Torimoto, Yoshihiro; Yonemura, Yuji; Hanaoka, Nobuyoshi; Nakakuma, Hideki; Hasegawa, Daisuke; Manabe, Atsushi; Fujishima, Naohito; Fujii, Nobuharu; Tanimoto, Mitsune; Morita, Yasuyoshi; Matsuda, Akira; Fujieda, Atsushi; Katayama, Naoyuki; Ohashi, Haruhiko; Nagai, Hirokazu; Terada, Yoshiki; Hino, Masayuki; Sato, Ken; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Ohta, Masatsugu; Imataki, Osamu; Uemura, Makiko; Takaku, Tomoiku; Komatsu, Norio; Kitanaka, Akira; Shimoda, Kazuya; Watanabe, Kenichiro; Tohyama, Kaoru; Takaori-Kondo, Akifumi; Harigae, Hideo; Arai, Shunya; Miyazaki, Yasushi; Ozawa, Keiya; Kurokawa, Mineo

    2017-09-11

    Hypoplastic myelodysplastic syndrome (hMDS) is a distinct entity with bone marrow (BM) hypocellularity and the risk of death from BM failure (BMF). To elucidate the characteristics of hMDS, the data of 129 patients diagnosed between April 2003 and March 2012 were collected from 20 institutions and the central review team of the National Research Group on Idiopathic Bone Marrow Failure Syndromes, and compared with 115 non-hMDS patients. More RA and fewer CMMoL and RAEB-t in French-American-British (FAB) and more RCUD and MDS-U and fewer RCMD in World Health Organization (WHO) classifications were found in hMDS than non-hMDS with significant differences. The overall survival (OS) and AML progression-free survival (AML-PFS) of hMDS were higher than those of non-hMDS, especially in patients at age ≥50 and of lower risk in Revised International Prognostic Scoring System (IPSS-R). In competing risks analysis, hMDS exhibited decreased risk of AML-progression in lower IPSS or IPSS-R risk patients, and higher risk of death from BMF in patients at age ≥50. Poor performance status (PS ≥2) and high karyotype risks in IPSS-R (high and very high) were significant risk factors of death and AML-progression in Cox proportional hazards analysis. This article is protected by copyright. All rights reserved. © 2017 Wiley Periodicals, Inc.

  5. Tetralogy of Fallot and Hypoplastic Left Heart Syndrome – Complex Clinical Phenotypes Meet Complex Genetic Networks

    PubMed Central

    Lahm, Harald; Schön, Patric; Doppler, Stefanie; Dreßen, Martina; Cleuziou, Julie; Deutsch, Marcus-André; Ewert, Peter; Lange, Rüdiger; Krane, Markus

    2015-01-01

    In many cases congenital heart disease (CHD) is represented by a complex phenotype and an array of several functional and morphological cardiac disorders. These malformations will be briefly summarized in the first part focusing on two severe CHD phenotypes, hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot (TOF). In most cases of CHD the genetic origin remains largely unknown, though the complexity of the clinical picture strongly argues against a dysregulation which can be attributed to a single candidate gene but rather suggests a multifaceted polygenetic origin with elaborate interactions. Consistent with this idea, genome-wide approaches using whole exome sequencing, comparative sequence analysis of multiplex families to identify de novo mutations and global technologies to identify single nucleotide polymorphisms, copy number variants, dysregulation of the transcriptome and epigenetic variations have been conducted to obtain information about genetic alterations and potential predispositions possibly linked to the occurrence of a CHD phenotype. In the second part of this review we will summarize and discuss the available literature on identified genetic alterations linked to TOF and HLHS. PMID:26069455

  6. Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation

    PubMed Central

    Jones, Helen N.; Olbrych, Stephanie K.; Smith, Kathleen L.; Cnota, James F.; Habli, Mounira; Gonzales-Ramos, Osniel; Owens, Kathryn J; Hinton, Andrea C.; Polzin, William J.; Muglia, Louis J.; Hinton, Robert B.

    2015-01-01

    Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 grams, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases. PMID:26278057

  7. Hypoplastic occipital condyle and third occipital condyle: review of their dysembryology.

    PubMed

    Tubbs, R Shane; Lingo, Patrick Ryan; Mortazavi, Martin M; Cohen-Gadol, Aaron A

    2013-11-01

    Disruption or embryologic derailment of the normal bony architecture of the craniovertebral junction (CVJ) may result in symptoms. As studies of the embryology and pathology of hypoplasia of the occipital condyles and third occipital condyles are lacking in the literature, the present review was performed. Standard search engines were accessed and queried for publications regarding hypoplastic occipital condyles and third occipital condyles. The literature supports the notion that occipital condyle hypoplasia and a third occipital condyle are due to malformation or persistence of the proatlas, respectively. The Pax-1 gene is most likely involved in this process. Clinically, condylar hypoplasia may narrow the foramen magnum and lead to lateral medullary compression. Additionally, this maldevelopment can result in transient vertebral artery compression secondary to posterior subluxation of the occiput. Third occipital condyles have been associated with cervical canal stenosis, hypoplasia of the dens, transverse ligament laxity, and atlanto-axial instability causing acute and chronic spinal cord compression. Treatment goals are focused on craniovertebral stability. A better understanding of the embryology and pathology related to CVJ anomalies is useful to the clinician treating patients presenting with these entities.

  8. A thermodynamically consistent model for granular-fluid mixtures considering pore pressure evolution and hypoplastic behavior

    NASA Astrophysics Data System (ADS)

    Hess, Julian; Wang, Yongqi

    2016-11-01

    A new mixture model for granular-fluid flows, which is thermodynamically consistent with the entropy principle, is presented. The extra pore pressure described by a pressure diffusion equation and the hypoplastic material behavior obeying a transport equation are taken into account. The model is applied to granular-fluid flows, using a closing assumption in conjunction with the dynamic fluid pressure to describe the pressure-like residual unknowns, hereby overcoming previous uncertainties in the modeling process. Besides the thermodynamically consistent modeling, numerical simulations are carried out and demonstrate physically reasonable results, including simple shear flow in order to investigate the vertical distribution of the physical quantities, and a mixture flow down an inclined plane by means of the depth-integrated model. Results presented give insight in the ability of the deduced model to capture the key characteristics of granular-fluid flows. We acknowledge the support of the Deutsche Forschungsgemeinschaft (DFG) for this work within the Project Number WA 2610/3-1.

  9. Prenatal head growth and white matter injury in hypoplastic left heart syndrome.

    PubMed

    Hinton, Robert B; Andelfinger, Gregor; Sekar, Priya; Hinton, Andrea C; Gendron, Roxanne L; Michelfelder, Erik C; Robitaille, Yves; Benson, D Woodrow

    2008-10-01

    Children with hypoplastic left heart syndrome (HLHS) have an increased prevalence of central nervous system (CNS) abnormalities. The extent to which this problem is due to CNS maldevelopment, prenatal ischemia, postnatal chronic cyanosis and/or multiple exposures to cardiopulmonary bypass is unknown. To better understand the etiology of CNS abnormalities in HLHS, we evaluated 68 neonates with HLHS; in 28 cases, both fetal ultrasound and echocardiogram data were available to assess head size, head growth and aortic valve anatomy (atresia or stenosis). In addition, we evaluated neuropathology in 11 electively aborted HLHS fetuses. The mean head circumference percentile in HLHS neonates was significantly smaller than HLHS fetuses (22 +/- 2% versus 40 +/- 4%, p < 0.001). A significant decrease in head growth, defined as a 50% reduction in head circumference percentile, was observed in half (14/28) of HLHS fetuses and nearly a quarter (6/28) were already growth restricted (

  10. Prevention of postoperative pericardial adhesions in children with hypoplastic left heart syndrome.

    PubMed

    Salminen, Jukka T; Mattila, Ilkka P; Puntila, Juha T; Sairanen, Heikki I

    2011-02-01

    Reoperations for congenital cardiac defects are associated with an increased surgical risk due to adhesions. We compared the capability of a polytetrafluoroethylene (PTFE) membrane, synthetic polyethyleneglycol hydrogel (PEG), and a combination of them to prevent postoperative pericardial adhesions in patients with hypoplastic left heart syndrome (HLHS). Eighteen consecutive patients with HLHS were included. At the end of the Norwood I operation the cranial and the caudal half of the heart of each patient was randomized to receive a PTFE membrane, a synthetic PEG, a combination of them, or no treatment (control). Tenacity and density of adhesions, epicardial visibility, and adhesions between the heart and the sternum were analyzed semiquantitatively at a subsequent bidirectional Glenn operation. The PTFE membrane significantly decreased adhesion formation between the heart and the sternum (P<0.001). However, the PTFE membrane, with or without synthetic PEG, impaired epicardial visibility (P<0.05) when compared to synthetic PEG or controls. Synthetic PEG alone did not significantly reduce the formation of pericardial adhesions. Tenacity and density of adhesions were not affected by any of the treatment modalities. The PTFE membrane significantly decreases postoperative adhesions between the heart and the sternum, but impairs epicardial visibility. Synthetic PEG does not prevent formation of pericardial adhesions.

  11. Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome.

    PubMed

    Ricci, Marco; Xu, Yanji; Hammond, Harriet L; Willoughby, David A; Nathanson, Lubov; Rodriguez, Maria M; Vatta, Matteo; Lipshultz, Steven E; Lincoln, Joy

    2012-01-01

    Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome.

  12. Lung hypoplasia in newborn rabbits with a diaphragmatic hernia affects pulmonary ventilation but not perfusion.

    PubMed

    Flemmer, Andreas W; Thio, Marta; Wallace, Megan J; Lee, Katie; Kitchen, Marcus J; Kerr, Lauren; Roehr, Charles C; Fouras, Andreas; Carnibella, Richard; Jani, Jaccques C; DeKoninck, Philip; Te Pas, Arjan B; Pearson, James T; Hooper, Stuart B

    2017-09-01

    BackgroundA congenital diaphragmatic hernia (DH) can result in severe lung hypoplasia that increases the risk of morbidity and mortality after birth; however, little is known about the cardiorespiratory transition at birth.MethodsUsing phase-contrast X-ray imaging and angiography, we examined the cardiorespiratory transition at birth in rabbit kittens with DHs. Surgery was performed on pregnant New Zealand white rabbits (n=18) at 25 days' gestation to induce a left-sided DH. Kittens were delivered at 30 days' gestation, intubated, and ventilated to achieve a tidal volume (Vt) of 8 ml/kg in control and 4 ml/kg in DH kittens while they were imaged.ResultsFunctional residual capacity (FRC) recruitment and Vt in the hypoplastic left lung were markedly reduced, resulting in a disproportionate distribution of FRC into the right lung. Following lung aeration, relative pulmonary blood flow (PBF) increased equally in both lungs, and the increase in pulmonary venous return was similar in both control and DH kittens.ConclusionThese findings indicate that nonuniform lung hypoplasia caused by DH alters the distribution of ventilation away from hypoplastic and into normally grown lung regions. During transition, the increase in PBF and pulmonary venous return, which is vital for maintaining cardiac output, is not affected by lung hypoplasia.

  13. Zellweger syndrome with unusual findings: non-immune hydrops fetalis, dermal erythropoiesis and hypoplastic toe nails.

    PubMed

    Dursun, Ali; Gucer, Safak; Ebberink, M S; Yigit, Sule; Wanders, R J A; Waterham, H R

    2009-12-01

    The peroxisomal biogenesis disorders (PBDs) comprise the Zellweger spectrum disorders (i.e., Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease) and rhizomelic chondrodysplasia punctata. Peroxisomal biogenesis disorders can be caused by mutations in any of 13 currently known PEX genes, which encode peroxins involved in peroxisomal protein import and/or assembly of the organelle. We report here on a Turkish patient who presented with unusual clinical findings, that included non-immune hydrops, dermal erythropoiesis and hypoplastic toenails, as well as common dysmorphic features of Zellweger syndrome. The patient has also pulmonary hypoplasia, which has been reported in only a few patients with Zellweger syndrome. A peroxisomal biogenesis disorder was confirmed by enzyme analysis and abnormal very long-chain fatty acid (VLCFA) profiles in plasma and fibroblast and immunofluorescence microscopy studies. Subsequent molecular genetic analysis revealed a homozygous c.856C>T mutation (R268X) in the PEX3 gene, which made this patient the third to have a defect in this gene. In contrast to those of the two previously reported patients, the cells of this patient still contained peroxisomal membrane structures (ghosts), seen by immunofluorescence microscopy analysis. The case presented here and the two previously reported cases point out that a PEX3 gene defect may present with fairly heterogeneous clinical findings. This case also raises a possibility that hydrops fetalis may be associated with a PEX3 gene defect and that peroxisomal disorders can be considered in the etiology of hydrops fetalis as well as other cell organelle disorders when one is considering yet undiscovered complementation groups in peroxisomal disorders.

  14. Early results of neurodevelopment following hybrid stage I for hypoplastic left heart syndrome.

    PubMed

    Cheatham, Sharon L; Carey, Helen; Chisolm, Joanne L; Heathcock, Jill C; Steward, Deborah

    2015-03-01

    Motor skills and neurodevelopment in infants with hypoplastic left heart syndrome (HLHS) who have undergone Hybrid Stage I palliation is unknown. The purpose of this study is to assess early neurodevelopment in infants with HLHS after Hybrid Stage I palliation. Developmental assessment was performed in HLHS infants who underwent Hybrid Stage I palliation at 2 and 4 months of age using the Test of Infant Motor Performance, and at 6 months of age, prior to undergoing the second staged surgery, using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Results were compared to healthy control subjects and norm-referenced data. The HLHS group scored between -1 and -2 standard deviations (SD) below the mean at 2 months of age (p = 0.002), and within -1 SD of the mean, at 4 months of age (p = 0.0019), on the TIMP. Compared to the control group, composite motor skills were significantly lower at 6 months of age on the Bayley-III in the HLHS group (p = 0.0489), however, not significant for cognitive (p = 0.29) or language (p = 0.68). Percentile rank motor scores were 17 ± 20 % in the HLHS group compared to 85 ± 12 % for the healthy age-matched control group. Infants with HLHS who undergo Hybrid Stage I palliation score lower on standardized motor skill tests compared to healthy age-matched controls and the norm-referenced population. This suggests that infants with HLHS have poorer motor skill performance than typically developing infants at 6 months of age.

  15. [Hypoplastic left heart syndrome: 10 year experience with staged surgical management].

    PubMed

    Urcelay, Gonzalo; Arancibia, Francisca; Retamal, Javiera; Springmuller, Daniel; Clavería, Cristián; Garay, Francisco; Frangini, Patricia; González, Rodrigo; Heusser, Felipe; Arretz, Claudio; Zelada, Pamela; Becker, Pedro

    2016-01-01

    Hypoplastic left heart syndrome (HLHS) is a lethal congenital heart disease in 95% of non-treated patients. Surgical staging is the main form of treatment, consisting of a 3-stage approach, beginning with the Norwood operation. Long term survival of treated patients is unknown in our country. 1) To review our experience in the management of all patients seen with HLHS between January 2000 and June 2012. 2) Identify risk factors for mortality. Retrospective analysis of a single institution experience with a cohort of patients with HLHS. Clinical, surgical, and follow-up records were reviewed. Of the 76 patients with HLHS, 9 had a restrictive atrial septal defect (ASD), and 8 had an ascending aorta ≤2mm. Of the 65 out of 76 patients that were treated, 77% had a Norwood operation with pulmonary blood flow supplied by a right ventricle to pulmonary artery conduit, 17% had a Norwood with a Blalock-Taussig shunt, and 6% other surgical procedure. Surgical mortality at the first stage was 23%, and for Norwood operation 21.3%. For the period between 2000-2005, surgical mortality at the first stage was 36%, and between 2005-2010, 15% (P=.05). Actuarial survival was 64% at one year, and 57% at 5years. Using a multivariate analysis, a restrictive ASD and a diminutive aorta were high risk factors for mortality. Our immediate and long term outcome for staged surgical management of HLHS is similar to that reported by large centres. There is an improvement in surgical mortality in the second half of our experience. Risk factors for mortality are also identified. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. [Comparative results of Fontan surgery in patients with and without hypoplastic left heart syndrome].

    PubMed

    Becker Rencoret, Pedro; Besa Bandeira, Santiago; Riveros González, Sergio; Frangini Sanhueza, Patricia; Springmüller Pinto, Daniel; González Foretic, Rodrigo; Urcelay Montecinos, Gonzalo

    During the last few years, numerous patients with univentricular heart disease have been treated surgically with total cavopulmonary anastomosis according to a staged surgery protocol in our institution. To evaluate the perioperative outcomes and survival of patients with hypoplastic left heart syndrome (HLHS) after the Fontan procedure and compare them with other types of univentricular heart disease. A total of 102 patients underwent a Fontan procedure between April 1996 and March 2014, 25 with HLHS (group I), and 77 patients with other types of univentricular heart disease (group II). Groups survival, demographics, hemodinamic studies, morbimortality, mechanical ventilation, surgical drains, post-operative stay, isotopes score, pacemaker use, and requiriment of Fontan takedown were analyzed. Intraoperative mortality was 4% (n=1) for group I, and 7.8% (n=6) for group II (P=.451). A difference was only found in hospital length of stay (LOS), being 17 days (6-47) for group I and 12 days (5-103) for group II (P=.017). Mean follow-up was 4.24±2.08 years for group I, and 8.7±4.67 for group II. Survival rate at 8 years for both groups was 88%, and 81% at 10 years for group II. The Fontan procedure had similar mortality, but longer LOS, in patients with HLHS compared to those with another types of single ventricle anatomy. Long term survival was comparable between both groups. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Fetal Aortic Valvuloplasty for Evolving Hypoplastic Left Heart Syndrome: Postnatal Outcomes of the First 100 Patients

    PubMed Central

    Freud, Lindsay R.; McElhinney, Doff B.; Marshall, Audrey C.; Marx, Gerald R.; Friedman, Kevin G.; del Nido, Pedro J.; Emani, Sitaram M.; Lafranchi, Terra; Silva, Virginia; Wilkins-Haug, Louise E.; Benson, Carol B.; Lock, James E.; Tworetzky, Wayne

    2015-01-01

    Background Fetal aortic valvuloplasty (FAV) can be performed for severe mid-gestation aortic stenosis (AS) in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after FAV. The postnatal outcomes and survival of the BV patients, compared to those managed as HLHS, have not been reported. Methods and Results We included 100 patients who underwent FAV for severe mid-gestation AS with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and LV volume, were significantly larger in the BV group at the time of birth (p-values <0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank p=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic and/or mitral valve replacement. On most recent echocardiogram, the median LV end-diastolic volume z-score was +1.7 (range: -1.3, +8.2), and 80% had normal ejection fraction. Conclusions Short- and intermediate-term survival among patients who underwent FAV and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and on-going assessment is warranted. PMID:25052401

  18. Mortality-related resource utilization in the inpatient care of hypoplastic left heart syndrome.

    PubMed

    Danford, David A; Karels, Quentin; Kulkarni, Aparna; Hussain, Aysha; Xiao, Yunbin; Kutty, Shelby

    2015-10-22

    Quantifying resource utilization in the inpatient care of congenital heart diease is clinically relevant. Our purpose is to measure the investment of inpatient care resources to achieve survival in hypoplastic left heart syndrome (HLHS), and to determine how much of that investment occurs in hospitalizations that have a fatal outcome, the mortality-related resource utilization fraction (MRRUF). A collaborative administrative database, the Pediatric Health Information System (PHIS) containing data for 43 children's hospitals, was queried by primary diagnosis for HLHS admissions of patients ≤21 years old during 2004-2013. Institution, patient age, inpatient deaths, billed charges (BC) and length of stay (LOS) were recorded. In all, 11,122 HLHS admissions were identified which account for total LOS of 277,027 inpatient-days and $3,928,794,660 in BC. There were 1145 inpatient deaths (10.3%). LOS was greater among inpatient deaths than among patients discharged alive (median 17 vs. 12, p < 0.0001). BC were greater among inpatient deaths than among patients discharged alive (median 4.09 × 10(5) vs. 1.63 × 10(5), p < 0.0001). 16% of all LOS and 21% of all BC were accrued by patients who did not survive their hospitalization. These proportions showed no significant change year-by-year. The highest volume institutions had lower mortality rates, but there was no relation between institutional volume and the MRRUF. These data should alert providers and consumers that current practices often result in major resource expenditure for inpatient care of HLHS that does not result in survival to hospital dismissal. They highlight the need for data-driven critical review of standard practices to identify patterns of care associated with success, and to modify approaches objectively.

  19. Modified Hybrid Procedure in Hypoplastic Left Heart Syndrome: Initial Experience of a Center in Northeastern Brazil

    PubMed Central

    Faria, Renato Max; Pacheco, Juliana Torres; de Oliveira, Itamar Ribeiro; Vidal, José Madson; Rodrigues Junior, Anilton Bezerra; Costa, Ana Luiza Lafeta; Nina, Vinicius José da Silva; Cascudo, Marcelo Matos

    2017-01-01

    Introduction Although it only corresponds to 2.5% of congenital heart defects, hypoplastic left heart syndrome (HLHS) is responsible for more than 25% of cardiac deaths in the first week of life. Palliative surgery performed after the second week of life is considered an important risk factor in the treatment of HLHS. Objective The aim of this study is to describe the initial experience of a medical center in Northeastern Brazil with a modified off-pump hybrid approach for palliation of HLHS. Methods From November 2012 through November 2015, the medical records of 8 patients with HLHS undergoing hybrid procedure were retrospectively evaluated in a tertiary private hospital in Northeastern Brazil. The modified off-pump hybrid palliation consisted of stenting of the ductus arteriosus guided by fluoroscopy without contrast and banding of the main pulmonary artery branches. Demographic and clinical variables were recorded for descriptive analysis. Results Eight patients were included in this study, of whom 37.5% were female. The median age and weight at the time of the procedure was 2 days (p25% and p75% = 2 and 4.5 days, respectively) and 3150 g (p25% and p75% = 3077.5 g and 3400 g, respectively), respectively. The median length in intensive care unit stay was 6 days (p25% and p75% = 3.5% and 8 days, respectively). There were no in-hospital deaths. Four patients have undergone to the second stage of the surgical treatment of HLHS. Conclusion In this series, the initial experience with the modified off-pump hybrid procedure showed to be safe, allowing a low early mortality rate among children presenting HLHS. PMID:28832800

  20. Are the anomalous vertebral arteries more hypoplastic?: retrospective linear mixed model approach.

    PubMed

    Kim, Chulho; Sohn, Jong-Hee; Choi, Hui-Chul

    2017-08-29

    Small or hypoplastic vertebral artery (VA) is one of the risk factor for posterior circulation stroke. We assess whether various types of VA anomaly contribute to its diameter. We screened 238 patients who underwent neck CT and MR angiography within 1 month. A V1 anomaly was defined as the abnormal origin of the VA on a three-dimensional MR angiography and a V2 anomaly was defined as the VA not passing through the 6th cervical transverse foramen (TF) on an axial CT image. A linear mixed model was used to evaluate the determinants of VA size. Among participants, 24 (10.1%) subjects exhibited an anomalous VA and, of the 476 VAs examined, 11 (2.3%) had an aortic origin and 27 (5.7%) had an abnormal entrance into the C6 TF. Presence of the V1 anomaly was positively associated with the V2 anomaly (P for chi-square < 0.001) and a linear mixed model revealed that being male (0.2 mm larger, P = 0.015), having a right VA anomaly (0.3 mm smaller, P < 0.001), having a V1 anomaly (0.9 mm smaller, P < 0.001), and having a V2 anomaly (0.7 mm smaller, P < 0.001) were significant predictor of VA diameter. The diameters of VAs with an anomalous aortic origin or an abnormal entrance of the TF were significantly smaller than those of normal VAs. These findings suggest that anomalies of the VA detected in 3-dimensional CTA or MRA may be clues for vertebral artery hypoplasia.

  1. Neurodevelopmental outcomes for children with hypoplastic left heart syndrome at the age of 5 years.

    PubMed

    Brosig, Cheryl; Mussatto, Kathleen; Hoffman, George; Hoffmann, Raymond G; Dasgupta, Mahua; Tweddell, James; Ghanayem, Nancy

    2013-10-01

    This study aimed to determine the neurodevelopmental (ND) outcome for children with hypoplastic left heart syndrome (HLHS) at early school age. English-speaking patients who underwent the Norwood procedure between 2000 and 2005 were eligible at 4-6 years of age for ND testing. Of the 72 eligible patients, 44 (61 %) agreed to participate, and 37 completed ND testing before the close of the study. Three subjects were excluded from analyses due to late stroke. The ND testing included intelligence, visual motor integration, memory and motor and language skills. Parents and teachers completed measures of behavior and attention problems. Subjects' scores and parent/teacher ratings were converted to z-scores and compared with test norms. Higher scores on child measures represent better outcomes, whereas higher scores on parent and teacher rating scales indicate more problems. The average ND performance of the tested cohort fell within one standard deviation of the test norms for all measures. However, the subjects performed significantly lower than the test norms on measures of visual-motor integration, fine motor skills, memory, and word structure (z = -0.42 to -0.54; p < 0.005). On the parent and teacher completed measures, the subjects scored higher than the test norms on attention problems (z = 0.40-0.62; p < 0.005). Although the overall ND performance of the cohort was normal, the subjects showed relative weakness in visual motor and attention skills. Ongoing developmental monitoring of these children is recommended to guide interventions that may improve individual outcomes and to assess the impact of changes in clinical management strategies on functional outcomes.

  2. Neurodevelopmental Outcomes for Children With Hypoplastic Left Heart Syndrome at the Age of 5 Years

    PubMed Central

    Mussatto, Kathleen; Hoffman, George; Hoffmann, Raymond G.; Dasgupta, Mahua; Tweddell, James; Ghanayem, Nancy

    2014-01-01

    This study aimed to determine the neurodevelopmental (ND) outcome for children with hypoplastic left heart syndrome (HLHS) at early school age. English-speaking patients who underwent the Norwood procedure between 2000 and 2005 were eligible at 4–6 years of age for ND testing. Of the 72 eligible patients, 44 (61 %) agreed to participate, and 37 completed ND testing before the close of the study. Three subjects were excluded from analyses due to late stroke. The ND testing included intelligence, visual motor integration, memory and motor and language skills. Parents and teachers completed measures of behavior and attention problems. Subjects’ scores and parent/teacher ratings were converted to z-scores and compared with test norms. Higher scores on child measures represent better outcomes, whereas higher scores on parent and teacher rating scales indicate more problems. The average ND performance of the tested cohort fell within one standard deviation of the test norms for all measures. However, the subjects performed significantly lower than the test norms on measures of visual-motor integration, fine motor skills, memory, and word structure (z = −0.42 to −0.54; p < 0.005). On the parent and teacher completed measures, the subjects scored higher than the test norms on attention problems (z = 0.40–0.62; p < 0.005). Although the overall ND performance of the cohort was normal, the subjects showed relative weakness in visual motor and attention skills. Ongoing developmental monitoring of these children is recommended to guide interventions that may improve individual outcomes and to assess the impact of changes in clinical management strategies on functional outcomes. PMID:23503929

  3. Treatment of right ventricle to pulmonary artery conduit stenosis in infants with hypoplastic left heart syndrome.

    PubMed

    Münsterer, Andrea; Kasnar-Samprec, Jelena; Hörer, Jürgen; Cleuziou, Julie; Eicken, Andreas; Malcic, Ivan; Lange, Rüdiger; Schreiber, Christian

    2013-09-01

    To determine the incidence of right ventricle-to-pulmonary artery (RV-PA) conduit stenosis after the Norwood I operation in patients with hypoplastic left heart syndrome (HLHS), and to determine whether the treatment strategy of RV-PA conduit stenosis has an influence on interstage and overall survival. Ninety-six patients had a Norwood operation with RV-PA conduit between 2002 and 2011. Details of reoperations/interventions due to conduit obstruction prior to bidirectional superior cavopulmonary anastomosis (BSCPA) were collected. Overall pre-BSCPA mortality was 17%, early mortality after Norwood, 6%. Early angiography was performed in 34 patients due to desaturation at a median of 8 days after the Norwood operation. Fifteen patients (16%) were diagnosed with RV-PA conduit stenosis that required treatment. The location of the conduit stenosis was significantly different in the patients with non-ringed (proximal) and the patients with ring-enforced conduit (distal), P = 0.004. In 6 patients, a surgical revision of the conduit was performed; 3 of them died prior to BSCPA. Another 6 patients had a stent implantation and 3 were treated with balloon dilatation followed by a BSCPA in the subsequent 2 weeks. All patients who were treated interventionally for RV-PA conduit obstruction had a successful BSCPA. Patients who received a surgical RV-PA conduit revision had a significantly higher interstage (P = 0.044) and overall mortality (P = 0.011) than those who received a stent or balloon dilatation of the stenosis followed by an early BSCPA. RV-PA conduit obstruction after Norwood I procedure in patients with HLHS can be safely and effectively treated by stent implantation, balloon dilatation and early BSCPA. Surgical revision of the RV-PA conduit can be reserved for patients in whom an interventional approach fails, and an early BSCPA is not an option.

  4. Vasoreactive Response to Maternal Hyperoxygenation (MH) in the Fetus with Hypoplastic Left Heart Syndrome (HLHS)

    PubMed Central

    Szwast, Anita; Tian, Zhiyun; McCann, Margaret; Donaghue, Denise; Rychik, Jack

    2011-01-01

    Background Cardio-pulmonary interactions play an important role in the pathophysiology of hypoplastic left heart syndrome (HLHS). Pulmonary vasculopathy has been identified, especially in those with restrictive/intact atrial septum (R/IAS). Responsiveness of the pulmonary vasculature to maternal hyperoxygenation (MH) may provide a tool to assess the degree of pulmonary vasculopathy present prior to birth. Methods and Results Doppler echocardiography was performed in 27 normal and 43 HLHS fetuses. In HLHS, sampling was repeated after 10 minutes of MH with 60% FiO2, and after 5 minutes of recovery. Sampling was performed in the proximal, mid-portion, and distal branch pulmonary artery (PA). Pulsatility index (PI) was used as a measure of vascular impedance. Of the HLHS fetuses, 34 had an open inter-atrial septum and 9 had a R/IAS. At birth, 5 fetuses underwent immediate intervention on the inter-atrial septum. Middle cerebral artery PI was lower in HLHS vs. normals (p<0.001). There was no difference in umbilical artery, ductus arteriosus, or branch PA PI between normals and HLHS. MH led to a significant decrease in PI at each of the PA sites sampled in fetuses with an open atrial septum (p<0.001); however, there no was significant change in the PI in fetuses that required immediate intervention on the atrial septum at birth. Using a cutoff value of <10% vasoreactivity, the sensitivity of MH testing for determining need for immediate intervention at birth is 100% [0.46-1.0], specificity 94% [0.78-.99], positive predictive value 71% [0.30-0.95], and negative predictive value 100% [0.86-1.0]. No untoward effects were seen with MH. Conclusions PA vasoreactivity to MH occurs in the fetus with HLHS. MH testing accurately identifies fetuses requiring urgent postnatal intervention at birth and may be used to select candidates for fetal atrial septoplasty. PMID:20044513

  5. Right ventricular mechanical dyssynchrony and asymmetric contraction in hypoplastic heart syndrome are associated with tricuspid regurgitation.

    PubMed

    Bharucha, Tara; Khan, Rubeena; Mertens, Luc; Friedberg, Mark K

    2013-10-01

    Right ventricular (RV) dysfunction and tricuspid regurgitation (TR) are associated with adverse outcome in hypoplastic left heart syndrome (HLHS) but remain poorly understood. The aim of this study was to assess RV longitudinal strain and mechanical dyssynchrony in HLHS in relation to TR. The hypothesis was that inhomogeneous RV contraction and mechanical dyssynchrony around the tricuspid valve apparatus may be associated with TR in some patients with HLHS. Echocardiograms of children aged 0 to 2 years with HLHS at all stages of surgical palliation were retrospectively reviewed for anatomic subtype and severity of TR. RV peak strain and dyssynchrony were assessed by vector velocity imaging. Sixty echocardiograms of patients with a median age of 0.54 years (interquartile range, 0.04-1.63 years) and a median weight 6.40 kg (interquartile range, 3.70-10.45 kg) demonstrated TR, which was absent or trivial in 25 (42%), mild in 20 (33%), moderate in five (8%), and severe in 10 (17%). The difference in peak longitudinal strain between the RV free wall and the septum or left-sided RV wall was significantly higher in patients with moderate or severe TR compared with no, trivial, or mild TR (2.93 ± 6.03% vs 0.16 ± 6.6%, P = .04). The difference in time to peak longitudinal strain between walls was significantly longer in moderate or severe TR compared with no, trivial, or mild TR (57.4 ± 145.1 vs 15.8 ± 75.9 msec, P = .04). There was a significant difference in anatomic subtype between patients with the most difference in peak strain compared with those with the least. RV mechanical dyssynchrony and inhomogeneous contraction are worse in patients with clinically important TR and HLHS. Copyright © 2013 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.

  6. Staged surgical management of hypoplastic left heart syndrome: a single institution 12 year experience

    PubMed Central

    McGuirk, S P; Griselli, M; Stumper, O F; Rumball, E M; Miller, P; Dhillon, R; de Giovanni, J V; Wright, J G; Barron, D J; Brawn, W J

    2006-01-01

    Objective To describe a 12 year experience with staged surgical management of the hypoplastic left heart syndrome (HLHS) and to identify the factors that influenced outcome. Methods Between December 1992 and June 2004, 333 patients with HLHS underwent a Norwood procedure (median age 4 days, range 0–217 days). Subsequently 203 patients underwent a bidirectional Glenn procedure (stage II) and 81 patients underwent a modified Fontan procedure (stage III). Follow up was complete (median interval 3.7 years, range 32 days to 11.3 years). Results Early mortality after the Norwood procedure was 29% (n  =  95); this decreased from 46% (first year) to 16% (last year; p < 0.05). Between stages, 49 patients died, 27 before stage II and 22 between stages II and III. There were one early and three late deaths after stage III. Actuarial survival (SEM) was 58% (3%) at one year and 50% (3%) at five and 10 years. On multivariable analysis, five factors influenced early mortality after the Norwood procedure (p < 0.05). Pulmonary blood flow supplied by a right ventricle to pulmonary artery (RV‐PA) conduit, arch reconstruction with pulmonary homograft patch, and increased operative weight improved early mortality. Increased periods of cardiopulmonary bypass and deep hypothermic circulatory arrest increased early mortality. Similar factors also influenced actuarial survival after the Norwood procedure. Conclusion This study identified an improvement in outcome after staged surgical management of HLHS, which was primarily attributable to changes in surgical technique. The RV‐PA conduit, in particular, was associated with a notable and independent improvement in early and actuarial survival. PMID:15939721

  7. Tracheostomy Among Infants With Hypoplastic Left Heart Syndrome Undergoing Cardiac Operations: A Multicenter Analysis.

    PubMed

    Prodhan, Parthak; Agarwal, Amit; ElHassan, Nahed O; Bolin, Elijah H; Beam, Brandon; Garcia, Xiomara; Gaies, Michael; Tang, Xinyu

    2017-04-01

    Less than 2.7% of infants undergoing congenital heart disease operations have difficulty weaning from invasive mechanical ventilation. In such instances, clinicians may choose to perform tracheostomy. Limited literature has examined tracheostomy placement specifically in infants with hypoplastic left heart syndrome (HLHS). This study evaluated the risk factors for tracheostomy placement in infants with HLHS and examined the outcomes of these infants before their first hospital discharge. This retrospective analysis of the Pediatric Heath Information System data set included infants with HLHS who underwent stage 1 Norwood operation, a hybrid procedure, or heart transplant from 2004 through 2013. We identified 5721 infants with HLHS, and 126 underwent tracheostomy placement. Infants in the tracheostomy group had more morbidities and a higher mortality rate across the study period. Diagnosis of chromosomal abnormalities, anomalies of the trachea and esophagus, larynx, diaphragm and nervous system, bilateral vocal cord paralysis, and necrotizing enterocolitis, and procedures including extracorporeal membrane oxygenation support, cardiac catheterization, and gastrostomy tube were independently associated with tracheostomy placement in the study population. Despite an overall increase in rates of tracheostomy performed in infants with HLHS during the study period, the mortality rate did not improve among tracheostomy patients. Several risk factors were identified in infants with HLHS in whom a tracheostomy was placed during their first hospitalization. Despite an overall increase in rates of tracheostomies during the study period, the mortality rate did not improve among these patients. Appropriate family counseling and thorough preoperative case selection is suggested when discussing possible tracheostomy placement in infants with HLHS. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  8. Prenatal diagnosis, birth location, surgical center, and neonatal mortality in infants with hypoplastic left heart syndrome.

    PubMed

    Morris, Shaine A; Ethen, Mary K; Penny, Daniel J; Canfield, Mark A; Minard, Charles G; Fixler, David E; Nembhard, Wendy N

    2014-01-21

    Most studies have not demonstrated improved survival after prenatal diagnosis of critical congenital heart disease, including hypoplastic left heart syndrome (HLHS). However, the effect of delivery near a cardiac surgical center (CSC), the recommended action after prenatal diagnosis, on HLHS mortality has been poorly investigated. Using Texas Birth Defects Registry data, 1999 through 2007, which monitored >3.4 million births, we investigated the association between distance (calculated driving time) from birth center to CSC and neonatal mortality in 463 infants with HLHS. Infants with extracardiac birth defects or genetic disorders were excluded. The associations between prenatal diagnosis, CSC HLHS volume, and mortality were also examined. Neonatal mortality in infants born <10 minutes from a CSC was 21.0%, 10 to 90 minutes 25.2%, and >90 minutes 39.6% (P for trend <0.001). Prenatal diagnosis alone was not associated with improved survival (P=0.14). In multivariable analysis, birth >90 minutes from a CSC remained associated with increased mortality (odds ratio, 2.03; 95% confidence interval, 1.19-3.45), compared with <10 minutes. In subanalysis, birth >90 minutes from a CSC was associated with higher pretransport mortality (odds ratio, 6.69; 95% confidence interval, 2.52-17.74) and birth 10 to 90 minutes with higher presurgical mortality (odds ratio, 4.45; 95% confidence interval, 1.17-17.00). Higher surgical mortality was associated with lower CSC HLHS volume (odds ratio per 10 patients, 0.88; 95% confidence interval, 0.84-0.91). Infants with HLHS born far from a CSC have increased neonatal mortality, and most of this mortality is presurgical. Efforts to improve prenatal diagnosis of HLHS and subsequent delivery near a large volume CSC may significantly improve neonatal HLHS survival.

  9. Aggressive Patch Augmentation May Reduce Growth Potential of Hypoplastic Branch Pulmonary Arteries After Tetralogy of Fallot Repair.

    PubMed

    Wilder, Travis J; Van Arsdell, Glen S; Pham-Hung, Eric; Gritti, Michael; Hussain, Sara; Caldarone, Christopher A; Redington, Andrew; Hickey, Edward J

    2016-03-01

    Potential surgical strategies for hypoplastic branch pulmonary arteries (BPAs) during tetralogy of Fallot repair include (1) extensive patch augmentation to the hilum (PATCH), (2) limited extension arterioplasty to the proximal pulmonary artery (EXTENSION), or (3) leaving the native vessels unaugmented (NATIVE). We explored the effect of these strategies on reintervention and BPA growth. From 2000 to 2012, 434 children underwent complete tetralogy of Fallot repair. Risk-adjusted parametric models were used to analyze the risk of BPA reintervention for (1) all children, (2) children with BPAs of 4 mm or smaller, and (3) children with BPAs of 3 mm or smaller. Repeated-measures analysis of more than 2,000 echocardiograms was used to characterize postoperative BPA growth and right ventricular pressure by using nonlinear mixed models. Overall survival (99% [3 deaths]) was excellent. The 10-year freedom from BPA reintervention was 84%. In risk-adjusted models (including baseline BPA z-score), PATCH had a decreased freedom from reintervention (73%; p < 0.01) vs EXTENSION (87%) or NATIVE (91%). For children with BPAs of 4 mm or smaller (28 PATCH, 60 EXTENSION, 75 NATIVE), baseline characteristics were similar. The risk-adjusted 5-year freedom from reintervention was 68% for PATCH, 76% for EXTENSION, and 85% for NATIVE. PATCH trended toward an increased risk of reintervention (p = 0.07). For children with BPAs of 4 mm or smaller left in their NATIVE state, only ∼15% required reintervention. After adjustment for baseline BPA z-score, the time-related BPA growth was decreased (p < 0.014) and right ventricular pressure was increased (p = 0.03) for the PATCH group. Aggressive PATCH augmentation of hypoplastic BPAs improves the short-term geometry but may lead to late stenosis and higher rates of reintervention. Hypoplastic BPAs in tetralogy of Fallot tend (∼85%) to grow well without instrumentation. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier

  10. Ventriculoarterial coupling in palliated hypoplastic left heart syndrome: Noninvasive assessment of the effects of surgical arch reconstruction and shunt type.

    PubMed

    Biglino, Giovanni; Giardini, Alessandro; Ntsinjana, Hopewell N; Schievano, Silvia; Hsia, Tain-Yen; Taylor, Andrew M

    2014-10-01

    To assess the coupling efficiency in hypoplastic left heart syndrome, considering the effect of surgical arch reconstruction and the shunt type received during the Norwood procedure. Ventriculoarterial coupling was assessed before Fontan completion in 32 patients with hypoplastic left heart syndrome (19 modified Blalock-Taussig and 13 Sano shunts at stage 1). Cardiovascular magnetic resonance data were analyzed, deriving functional parameters and 3-dimensional volumes. Dimensional indexes were computed from 3-dimensional data sets as the area ratio of the isthmus to the descending aorta (Risthmus) and the isthmus to surgically enlarged transverse arch (Rarch). Wave intensity was calculated from cardiac magnetic resonance, using the peaks of the forward compression and expansion waves in early and late systole as surrogate indicators of ventriculoarterial coupling. Aortic distensibility (3.6±2.7×10(-3) 1/mm Hg) was not associated with the time elapsed from stage 1 palliation (P=.94), suggesting an early loss of elasticity that did not progress thereafter. Risthmus was 1.0±0.4, and Rarch was 0.3±0.1, indicating the dilated reconstructed arch was the main anatomic feature. The forward compression wave correlated significantly with Rarch (R2=0.23, P=.006) but not with Risthmus (R2<0.01, P=.63). Patients with a reduced ejection fraction exhibited a larger ventricular mass (R2=0.28, P=.003). The Sano shunt patients had a lower ejection fraction (51%±6% vs 57%±6%, P=.02); however, neither the forward compression nor expansion wave varied significantly between shunt type or the other functional parameters. Ventriculoarterial coupling in operated hypoplastic left heart syndrome was affected by aortic arch size mismatch but not by the type of shunt placed at the Norwood operation. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  11. Ultrasound assessment of mesenteric blood flow in neonates with hypoplastic left heart before and after hybrid palliation.

    PubMed

    Cozzi, Corin T; Galantowicz, Mark; Cheatham, John P; Nicholson, Lisa; Fernandez, Richard; Backes, Carl H; McCaw, Carrie; Cua, Clifford L

    2015-08-01

    Altered mesenteric perfusion may be a contributor to the development of necrotising enterocolitis in patients with hypoplastic left heart syndrome. The goal of this study was to document mesenteric flow patterns in patients with hypoplastic left heart syndrome pre- and post-hybrid procedure. A prospective study on all patients with hypoplatic left heart syndrome undergoing the hybrid procedure was conducted. Doppler ultrasound analysis of the coeliac and superior mesenteric artery was performed. A total of 13 patients were evaluated. There was a significant difference in the coeliac artery effective velocity-time intergral pre- and post-hybrid procedure (8.69±3.84 versus 12.51±4.95 cm, respectively). There were significant differences in the superior mesenteric artery antegrade velocity-time integral pre- and post-hybrid procedure (6.86±2.45 versus 10.52±2.64 cm, respectively) and superior mesenteric artery effective velocity-time integral pre- and post-hybrid procedure (6.22±2.68 versus 9.73±2.73 cm, respectively). There were no significant differences between the coeliac and superior mesenteric artery Doppler indices in the pre-hybrid procedure; there were, however, significant differences in the post-hybrid procedure between coeliac and superior mesenteric artery antegrade velocity-time integral (13.8 2±5.60 versus 10.52±2.64 cm, respectively) and effective velocity-time integral (13.04±4.71 versus 9.73±2.73 cm, respectively). Doppler mesenteric indices of perfusion improve in patients with hypoplastic left heart syndrome after the hybrid procedure; however, there appears to be preferential flow to the coeliac artery versus the superior mesenteric artery in these patients post-procedure.

  12. Hypoplastic thyroid, growth hormone deficiency, corneal opacities, cataract and hyperkeratotic skin disease: a possible new ichthyosis syndrome associated with endocrinopathies.

    PubMed

    Pichler, Robert; Stelzer, Christoph; Berg, Jörg; Holzinger, Carl; Eckl, Katja Martina; Hennies, Hans Christian; Auböck, Josef

    2005-06-01

    A 56 year old man presented with ichthyosis vulgaris since early childhood, clinically characterised by fine scaling of the trunk and hyperkeratotic scales on the exterior surfaces of the upper and lower extremities. The patient also showed hypothyroidism due to hypoplastic thyroid, cataract, hypercholesterinemia with concommitant arcus cornealis and biliary concrements. Renal lithiasis caused by calcio-oxalate was additionally present. Endocrinological screening revealed growth hormone deficiency in the 1.55 m tall man-(secondary) osteoporosis was observed. The clinical symptomatology indicates that this case cannot be considered as a subtype of the inherited ichthyosis group, but suggests a new syndrome as a separate nosologic entity.

  13. Technical Description of the Use of Selective Perfusion Techniques During the Norwood Procedure for Hypoplastic Left Heart Syndrome

    PubMed Central

    Chabot, David Leonard; Polimenakos, Anastasios C.

    2011-01-01

    Abstract: Since the introduction of the Norwood procedure for surgical palliation of hypoplastic left heart syndrome in 1983, refinements have been made to the original procedure to improve patient outcomes while still accomplishing the original goals of the procedure. One of these refinements has been the introduction of regional selective perfusion to limit the duration of circulatory arrest times and optimize the regional flow distribution. In this paper we describe our technique for performing selective cerebral and lower body perfusion during the Norwood procedure. PMID:22416608

  14. Clinical course and interstage monitoring after the Norwood and hybrid procedures for hypoplastic left heart syndrome.

    PubMed

    Knirsch, Walter; Bertholdt, Sonia; Stoffel, Gaby; Stiasny, Brian; Weber, Roland; Dave, Hitendu; Prêtre, Rene; von Rhein, Michael; Kretschmar, Oliver

    2014-06-01

    Infants with hypoplastic left heart syndrome (HLHS) are at risk for interstage morbidity and mortality, especially between the first and second surgical stages after the Norwood and hybrid procedures. This study compared the morbidity and mortality of patients treated by either the Norwood or the hybrid procedure for HLHS between the first and second stages who were undergoing interstage monitoring. Between October 2008 and December 2011, 26 infants (14 boys) with HLHS (n = 16) and other univentricular heart malformations with aortic arch anomaly (n = 10) were scheduled for interstage monitoring after Norwood I (n = 12) and hybrid (n = 14) procedures. Three infants (11.5 %) died after first-stage palliation (one hybrid patient and two Norwood patients), and three infants (11.5 %) died after second-stage palliation (two hybrid patients and one Norwood patient) (p = 0.83), all after early second-stage surgery (<90 days). The Norwood I and hybrid procedures did not differ in terms of overall mortality (23 %) (three hybrid and three Norwood patients; p = 1.00). Seven infants (26.9 %) could not be discharged from the hospital due to hemodynamic instability and were referred for early second-stage surgery (<90 days). After the first stage, the invasive reevaluation rate before discharge was high (53.8 %), with cardiac catheterizations for 8 of 14 patients after the hybrid procedure and for 6 of 12 patients after the Norwood procedure (p = 0.69). A total of 11 reinterventions were performed (eight by catheter and three by surgery). Of the eight catheter reinterventions, five were performed for hybrid patients (p = 0.22). For 14 infants, 89 days (range 10-177 days) of interstage monitoring were scheduled. One infant (3.9 %) died during the interstage monitoring. The findings showed a breach of the physiologic criteria for interstage monitoring in seven infants (50 %) after 10 days (range 4-68 days) (five hybrid and two Norwood patients), leading to rehospitalization and

  15. Impact of Norwood versus hybrid palliation on cardiac size and function in hypoplastic left heart syndrome.

    PubMed

    Grotenhuis, Heynric B; Ruijsink, Bram; Chetan, Devin; Dragulescu, Andreea; Friedberg, Mark K; Kotani, Yasuhiro; Caldarone, Christopher A; Honjo, Osami; Mertens, Luc L

    2016-06-15

    The hybrid approach for hypoplastic left heart syndrome (HLHS) could theoretically result in better preservation of right ventricular (RV) function then the Norwood procedure. The aim of this study was to compare echocardiographic indices of RV size and function in patients after Norwood and hybrid throughout all stages of palliation. 76 HLHS patients (42 Norwood, 34 hybrid) were retrospectively studied. Echocardiography was obtained before stage I, before and after stage II, and before and after Fontan. Median follow-up was 4.9 years (range 1.1-8.5). Baseline characteristics before stage I were similar. Hybrid patients demonstrated a significant decrease in RV fractional area change (FAC) between baseline and pre-stage II (36±9% vs 27±6%; p<0.01); Norwood patients remained stable (32±10% vs 32±7%; p=0.21). At pre-stage II, moderate/severe tricuspid valve (TV) regurgitation was found in nine Norwood (33%) and four hybrid (18%) patients (p=0.19). After stage II, the difference in FAC became insignificant (29±7% vs 25±8%, p=0.08) and moderate/severe TV regurgitation (TR) was found in 13 Norwood (48%) and four hybrid patients (19%) (p=0.18). At pre-Fontan, RV FAC was similar after Norwood and hybrid (34±5% vs 33±6%, p=0.69), which remained unchanged after Fontan. After Fontan, one Norwood and one hybrid patient had moderate TR. RV and TV size were similar for both groups at each time point. Patients after Norwood and hybrid procedures had equivalent indices of RV size, and systolic and diastolic function throughout all stages of palliation. Small differences in individual RV and TV indices are likely to be explained by differences in physiology or surgical timing rather than by intrinsic differences in myocardial and valve function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Transcatheter Arterial Embolization Therapy for a Hypoplastic Pelvic Kidney with a Single Vaginal Ectopic Ureter to Control Incontinence: The Usefulness of Three-Dimensional CT Angiography Using Multidetector-Row Helical CT

    SciTech Connect

    Kudoh, Kouichi Kadota, Masataka; Nakayama, Yoshiharu; Imuta, Masanori; Yasuda, Tsuyoshi; Yamashita, Yasuyuki; Inadome, Akito; Yoshida, Masaki; Ueda, Shouichi

    2003-09-15

    A girl with continuous urinary incontinence was successfully treated by angiographic embolization of a hypoplastic pelvic kidney with a single unilateral vaginal ectopic opening of the ureter. For this intervention, CT angiography was useful for detecting the corresponding renal artery of the hypoplastic kidney.

  17. [Management of High-Risk Prostate Cancer and Left Ectopic Ureter Inserting into Seminal Vesicle with Ipsilateral Hypoplastic Kidney of a Young Patient : A Case Report].

    PubMed

    Matsumoto, Teppei; Koie, Takuya; Soma, Osamu; Kusaka, Ayumu; Hosogoe, Shogo; Hamano, Itsuto; Imai, Atsushi; Hatakeyama, Shingo; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Ohyama, Chikara

    2016-06-01

    A 44-year-old male patient visited our hospital with a chief complaint of macroscopic hematuria. Prostate biopsies were performed due to prostate specific antigen (PSA) 11.6 ng/ml, and he was diagnosed with Gleason score 5+4 prostate cancer. Computed tomography showed a left hypoplastic kidney. T2- weighted magnetic resonance imaging showed the left ureter stump with ectopic insertion into the dilated left seminal vesicle. He was diagnosed with high-risk prostate cancer and left ectopic ureter inserting into the seminal vesicle with ipsilateral hypoplastic kidney. Laparoscopic left nephroureterectomy and open radical prostatectomy were performed.

  18. Twin-twin transfusion syndrome, coarctation of the aorta and hypoplastic aortic arch: a case series report.

    PubMed

    van den Boom, Jutta; Battin, Malcolm; Hornung, Tim

    2010-03-01

    The twin-twin transfusion syndrome (TTTS) complicates 10-30% of monochorionic pregnancies. The incidence of pulmonary stenosis and endocardial fibroelastosis is especially high in the recipient twin. We report a novel finding of four cases of coarctation of the aorta and hypoplastic aortic arch in the donor to raise awareness of cardiac lesions in twins affected by TTTS. Retrospective review of both neonatal database and mortality data from 2002 to 2007 with cross-validation from the local tertiary cardiology unit data (1998-2006) to identify children presenting with coarctation who were also twins. We identified four monochorionic twin pairs affected by the TTTS, delivered between 25 weeks and 36 weeks' gestation, where the donor was found to have coarctation of the aorta or a hypoplastic aortic arch. In addition, two of the four recipients also had cardiac abnormalities. There was a high mortality rate of 30% for both twins, and a high morbidity rate, especially for neurological sequelae. We believe that the types of abnormalities seen may be explained by the altered fetal blood flow and haemodynamics in TTTS. Given the increased prevalence of congenital heart disease in TTTS, with an increased risk of coarctation in the donor twin and pulmonary stenosis in the recipient, intra-uterine surveillance and a post-natal comprehensive cardiac assessment for both twins is warranted.

  19. Combination of cor triatriatum sinistrum and hypoplastic left heart syndrome in Meckel-Gruber syndrome: a case report.

    PubMed

    Taweevisit, Mana; Treetipsatit, Jitsupa; Tantbirojn, Patou; Thorner, Paul Scott

    2009-01-01

    Meckel-Gruber syndrome (MKS) is a fatal, autosomal recessive disorder characterized by malformation of central nervous system, particularly occipital encephalocele, bilateral renal dysplasia, and polydactyly. However, the clinical findings of this syndrome encompass various organ abnormalities as a result of genetic heterogeneity. The associated heart anomaly in MKS is inconstant. Its prevalence is rare and no striking or specific cardiac defects have been documented. We present a case of MKS with combined cor triatriatum sinistrum (left atrium divided into upper and lower compartment by a thin membrane) and hypoplastic left heart syndrome (underdeveloped mitral valve, left ventricle, and aorta) in a 33-week male fetus that was ultrasonographically detected and confirmed by autopsy. In addition to the cardiac defects, the patient was found to have postaxial polydactyly of 4 extremities, Dandy-Walker malformation, bilateral renal cystic dysplasia, and hepatic plate malformation. To the best of our knowledge, this is the first time that a combination of cor triatriatum sinistrum and hypoplastic left heart syndrome in MKS has been reported in the literature.

  20. Fetal reprogramming and senescence in hypoplastic left heart syndrome and in human pluripotent stem cells during cardiac differentiation.

    PubMed

    Gaber, Naila; Gagliardi, Mark; Patel, Pranali; Kinnear, Caroline; Zhang, Cindy; Chitayat, David; Shannon, Patrick; Jaeggi, Edgar; Tabori, Uri; Keller, Gordon; Mital, Seema

    2013-09-01

    Hypoplastic left heart syndrome (HLHS) is a severe cardiac malformation characterized by left ventricle (LV) hypoplasia and abnormal LV perfusion and oxygenation. We studied hypoxia-associated injury in fetal HLHS and human pluripotent stem cells during cardiac differentiation to assess the effect of microenvironmental perturbations on fetal cardiac reprogramming. We studied LV myocardial samples from 32 HLHS and 17 structurally normal midgestation fetuses. Compared with controls, the LV in fetal HLHS samples had higher nuclear expression of hypoxia-inducible factor-1α but lower angiogenic growth factor expression, higher expression of oncogenes and transforming growth factor (TGF)-β1, more DNA damage and senescence with cell cycle arrest, fewer cardiac progenitors, myocytes and endothelial lineages, and increased myofibroblast population (P < 0.05 versus controls). Smooth muscle cells (SMCs) had less DNA damage compared with endothelial cells and myocytes. We recapitulated the fetal phenotype by subjecting human pluripotent stem cells to hypoxia during cardiac differentiation. DNA damage was prevented by treatment with a TGF-β1 inhibitor (P < 0.05 versus nonhypoxic cells). The hypoplastic LV in fetal HLHS samples demonstrates hypoxia-inducible factor-1α up-regulation, oncogene-associated cellular senescence, TGF-β1-associated fibrosis and impaired vasculogenesis. The phenotype is recapitulated by subjecting human pluripotent stem cells to hypoxia during cardiac differentiation and rescued by inhibition of TGF-β1. This finding suggests that hypoxia may reprogram the immature heart and affect differentiation and development.

  1. Lung Transplant

    MedlinePlus

    Lung transplant Overview By Mayo Clinic Staff A lung transplant is a surgical procedure to replace a diseased or ... lung, usually from a deceased donor. A lung transplant is reserved for people who have tried other ...

  2. Lung surgery

    MedlinePlus

    ... lung tissue that is diseased or damaged from emphysema or bronchiectasis Remove blood or blood clots ( hemothorax ) ... Editorial team. Related MedlinePlus Health Topics Collapsed Lung Emphysema Lung Cancer Lung Diseases Pleural Disorders Browse the ...

  3. Lung Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  4. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  5. Pain management after comprehensive stage 2 repair for hypoplastic left heart syndrome.

    PubMed

    Naguib, Aymen N; Dewhirst, Elisabeth; Winch, Peter D; Simsic, Janet; Galantowicz, Mark; Tobias, Joseph D

    2013-01-01

    Achieving optimal pain control for children after complex cardiac surgery can be challenging. Recently, the hybrid approach to palliation of hypoplastic left heart syndrome (HLHS) was introduced as an alternative to the classic Norwood procedure. The second stage of the hybrid approach is a complex procedure known as comprehensive stage 2 (CS2). The authors have noted that pain control after the CS2 procedure is particularly difficult to manage. This report presents a review of the authors' pain management strategy in this clinical scenario and evaluates its efficacy. The medical records of patients who underwent CS2 repair of the hybrid procedure for HLHS between June 2008 and August 2011 were retrospectively reviewed. As a comparative group with a similar physiology, patients undergoing an isolated Glenn procedure also were reviewed. In addition to demographic data, the intraoperative use of narcotics and other adjunct medications for analgesia and sedation was recorded. Postoperatively, the mode of analgesia, the total opioid administered during the first 48 h postoperatively, and the nursing-assessed patient pain scores were recorded. Any adverse drug effect or need to adjust the analgesic regimen was recorded, as well as the timing of tracheal extubation. During the study period, 36 patients ranging in age from 4 to 14 months underwent the CS2 procedure, and 21 patients underwent a Glenn procedure. After CS2 repair, fentanyl was the opioid initially prescribed for all but 2 of the 21 patients managed with the nurse-controlled analgesia (NCA) delivery method and 15 patients managed with continuous infusion. After the Glenn shunt, all patients were prescribed NCA, with 20 patients receiving fentanyl and 1 patient receiving hydromorphone. The use of intraoperative dexmedetomidine caused a decrease in the total narcotic requirements, although this did not reach a statistical significance for either the extubated or intubated patients after CS2. The extubated

  6. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

  7. Technical modification enabling pulmonary valve-sparing repair of a severely hypoplastic pulmonary annulus in patients with tetralogy of Fallot.

    PubMed

    Ito, Hiroki; Ota, Noritaka; Murata, Masaya; Tosaka, Yuko; Ide, Yujiro; Tachi, Maiko; Sugimoto, Ai; Sakamoto, Kisaburo

    2013-06-01

    Although pulmonary valve-sparing repair is preferable for patients with tetralogy of Fallot, the repair of very small pulmonary valves is challenging. The present study evaluates our modification for preserving severely hypoplastic pulmonary valves in patients with tetralogy of Fallot. Sixty-eight consecutive patients who underwent complete repair of a tetralogy of Fallot between 2005 and 2011 were retrospectively reviewed. Patients with pulmonary atresia, absence of a pulmonary valve, atrioventricular septal defect and/or subarterial ventricular septal defect were excluded. There were 19 (28%) patients with a severely hypoplastic pulmonary annulus determined by preoperative echocardiography (z-score <-4). For these patients, we collected echocardiographic data and information about their postoperative course. Valve preserving was successful in 11 of 19 (58%) of the z < -4 group, compared with 48 of 49 (98%) of the z > -4 group. In the z < -4 valve-sparing subgroup (n = 11), the preoperative pulmonary valve diameter z-score was -4.9 (range -6.3 to -4.3), and an approach involving ventriculotomy with no transannular patch was employed at a mean age of 6.9 (range 2.2-16.1) months. In this subgroup, residual right ventricular outflow tract velocity was 2.4 ± 0.6 m/s at discharge from the hospital. During a mean follow-up of 2.6 ± 2.4 years, no reintervention was necessary. Late right ventricular outflow tract velocity was 2.2 ± 0.6 m/s, and there was no severe pulmonary regurgitation. The pulmonary valve annulus grew in relation to the patient's body surface area (z = -0.51, range -4.2-0.24) without any aneurysmal changes in the right ventricular outflow tract. Although our modification of valve-sparing repair for severely hypoplastic pulmonary valves in patients with tetralogy of Fallot could not be applied in all patients, this strategy enabled acceptable growth of the valve annulus, with only mild stenosis during the early to mid-term follow-up. This

  8. Technical modification enabling pulmonary valve-sparing repair of a severely hypoplastic pulmonary annulus in patients with tetralogy of Fallot†

    PubMed Central

    Ito, Hiroki; Ota, Noritaka; Murata, Masaya; Tosaka, Yuko; Ide, Yujiro; Tachi, Maiko; Sugimoto, Ai; Sakamoto, Kisaburo

    2013-01-01

    OBJECTIVES Although pulmonary valve-sparing repair is preferable for patients with tetralogy of Fallot, the repair of very small pulmonary valves is challenging. The present study evaluates our modification for preserving severely hypoplastic pulmonary valves in patients with tetralogy of Fallot. METHODS Sixty-eight consecutive patients who underwent complete repair of a tetralogy of Fallot between 2005 and 2011 were retrospectively reviewed. Patients with pulmonary atresia, absence of a pulmonary valve, atrioventricular septal defect and/or subarterial ventricular septal defect were excluded. There were 19 (28%) patients with a severely hypoplastic pulmonary annulus determined by preoperative echocardiography (z-score <−4). For these patients, we collected echocardiographic data and information about their postoperative course. RESULTS Valve preserving was successful in 11 of 19 (58%) of the z < −4 group, compared with 48 of 49 (98%) of the z > −4 group. In the z < −4 valve-sparing subgroup (n = 11), the preoperative pulmonary valve diameter z-score was −4.9 (range −6.3 to −4.3), and an approach involving ventriculotomy with no transannular patch was employed at a mean age of 6.9 (range 2.2–16.1) months. In this subgroup, residual right ventricular outflow tract velocity was 2.4 ± 0.6 m/s at discharge from the hospital. During a mean follow-up of 2.6 ± 2.4 years, no reintervention was necessary. Late right ventricular outflow tract velocity was 2.2 ± 0.6 m/s, and there was no severe pulmonary regurgitation. The pulmonary valve annulus grew in relation to the patient's body surface area (z = −0.51, range −4.2–0.24) without any aneurysmal changes in the right ventricular outflow tract. CONCLUSIONS Although our modification of valve-sparing repair for severely hypoplastic pulmonary valves in patients with tetralogy of Fallot could not be applied in all patients, this strategy enabled acceptable growth of the valve annulus, with only mild

  9. Uterine Adenomyosis Which Developed from Hypoplastic Uterus in Postmenopausal Woman with Mayer-Rokitansky-Kuster-Hauser Syndrome: A Case Report

    PubMed Central

    Chun, Sungwook; Kim, Yeon Mee

    2013-01-01

    Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by vaginal agenesis with variable Müllerian duct abnormalities. We report here a case of uterine adenomyosis which developed from a hypoplastic uterus in a patient with MRKHS. A 55-year-old postmenopausal woman visited a university hospital for pelvic mass. She had underwent vaginoplasty via the McIndoe procedure for MRKHS at 15 years of age. Pelvic magnetic resonance imaging showed a 5.4 × 4.8 × 4.7 cm mass suspicious for a uterine myoma. She received total abdominal hysterectomy with bilateral salpingo-oophorectomy, and neither the cervix nor endometrium was found grossly in the surgical specimen. The final histologic diagnosis was uterine adenomyosis. PMID:25371879

  10. Uterine adenomyosis which developed from hypoplastic uterus in postmenopausal woman with mayer-rokitansky-kuster-hauser syndrome: a case report.

    PubMed

    Chun, Sungwook; Kim, Yeon Mee; Ji, Yong-Il

    2013-12-01

    Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by vaginal agenesis with variable Müllerian duct abnormalities. We report here a case of uterine adenomyosis which developed from a hypoplastic uterus in a patient with MRKHS. A 55-year-old postmenopausal woman visited a university hospital for pelvic mass. She had underwent vaginoplasty via the McIndoe procedure for MRKHS at 15 years of age. Pelvic magnetic resonance imaging showed a 5.4 × 4.8 × 4.7 cm mass suspicious for a uterine myoma. She received total abdominal hysterectomy with bilateral salpingo-oophorectomy, and neither the cervix nor endometrium was found grossly in the surgical specimen. The final histologic diagnosis was uterine adenomyosis.

  11. Atrial septal defect of the persistent ostium primum type with hypoplastic right ventricle in a Welsh pony foal.

    PubMed Central

    Physick-Sheard, P W; Maxie, M G; Palmer, N C; Gaul, C

    1985-01-01

    Valvular competency of the foramen ovale (patent foramen ovale) is regarded as a common finding in the neonatal foal and usually occurs in isolation. True atrial septal defects appear to be uncommon and are usually associated with other congenital cardiac lesions. The present report describes a case of atrial septal defect type 1 (persistent ostium primum) complicated by hypoplastic right ventricle, and tricuspid dysplasia, in a Welsh Mountain pony foal, and discusses the embryogenesis of the abnormality. A critical review of the literature suggests that atrial septal defects may occur more frequently than they are reported, and that on occasion they may be described erroneously as patent foramen ovale. The clinical significance of uncomplicated discontinuity of the atrial septum is slight, depending upon the size and location of the defect. Complicated atrial septal defects vary in clinical significance according to the nature of the associated defects. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:4075243

  12. Hypoplastic model for simulation of compressibility characteristics of cement-admixed Bangkok soft clay at high water content

    NASA Astrophysics Data System (ADS)

    Chattonjai, Piyachat

    2016-06-01

    The developed hypoplastic model for simulation of compressibility characteristics of cement-admixed Bangkok soft clay at high water content was proposed in this paper. By using unique equation, the model is able to predict the relationship between void ratio and vertical effective stress of different water and cement content of soil cement. For practically convenient utilization and understanding, the parameters of Q1 which represented to initial cement bonding of soil (the initial value of structure tensor at time = 0) and C2 which effected to the model stiffness on isotropic consolidation direction, at 45° for loading and 225° for unloading of stress response envelope, were proposed as the function of cement and water content by comparing with dry weight of soil. By numerical integration that satisfied one-dimensional settlement, the simulation results were directly compared with fifteen experimental results to verify the accuracy of the proposed model.

  13. Translocation of the Aortic Arch with Norwood Procedure for Hypoplastic Left Heart Syndrome Variant with Circumflex Retroesophageal Aortic Arch

    PubMed Central

    Lee, Chee-Hoon; Seo, Dong Ju; Bang, Ji Hyun; Goo, Hyun Woo; Park, Jeong-Jun

    2014-01-01

    Retroesophageal aortic arch, in which the aortic arch crosses the midline behind the esophagus to the contralateral side, is a rare form of vascular anomaly. The complete form may cause symptoms by compressing the esophagus or the trachea and need a surgical intervention. We report a rare case of a hypoplastic left heart syndrome variant with the left retroesophageal circumflex aortic arch in which the left aortic arch, retroesophageal circumflex aorta, and the right descending aorta with the aberrant right subclavian artery encircle the esophagus completely, thus causing central bronchial compression. Bilateral pulmonary artery banding and subsequent modified Norwood procedure with extensive mobilization and creation of the neo-aorta were performed. As a result of the successful translocation of the aorta, the airway compression was relieved. The patient underwent the second-stage operation and is doing well currently. PMID:25207249

  14. Hybrid Stage I Procedure as Initial Palliation for Neonate With Hypoplastic Left Heart Syndrome and Right Congenital Diaphragmatic Hernia.

    PubMed

    Cvetkovic, Draginja; Giamelli, Joseph; Lyew, Michael; Erb, Markus; Sett, Suvro; DiStefano, Youmna

    2017-01-01

    During the past decade, a hybrid procedure has emerged and dramatically evolved as an alternative stage I palliation to the conventional Norwood procedure in neonates with hypoplastic left heart syndrome (HLHS). The hybrid approach avoids the need for cardiopulmonary bypass (CPB) utilizing stenting of the arterial duct and bilateral pulmonary artery banding. Cerebral and coronary perfusion pressure is maintained, and the pulmonary vasculature is protected from higher systemic pressure. Elimination of risks associated with CPB gains vital time to stabilize the patient and correct coexisting noncardiac anomalies and allows growth in preparation for the later stages of the Fontan pathway. The association of HLHS with right congenital diaphragmatic hernia (CDH) is rare. We report performing a successful hybrid stage I palliation on a neonate with HLHS and severe right CDH.

  15. Modeling single ventricle physiology: review of engineering tools to study first stage palliation of hypoplastic left heart syndrome.

    PubMed

    Biglino, Giovanni; Giardini, Alessandro; Hsia, Tain-Yen; Figliola, Richard; Taylor, Andrew M; Schievano, Silvia

    2013-10-30

    First stage palliation of hypoplastic left heart syndrome, i.e., the Norwood operation, results in a complex physiological arrangement, involving different shunting options (modified Blalock-Taussig, RV-PA conduit, central shunt from the ascending aorta) and enlargement of the hypoplastic ascending aorta. Engineering techniques, both computational and experimental, can aid in the understanding of the Norwood physiology and their correct implementation can potentially lead to refinement of the decision-making process, by means of patient-specific simulations. This paper presents some of the available tools that can corroborate clinical evidence by providing detailed insight into the fluid dynamics of the Norwood circulation as well as alternative surgical scenarios (i.e., virtual surgery). Patient-specific anatomies can be manufactured by means of rapid prototyping and such models can be inserted in experimental set-ups (mock circulatory loops) that can provide a valuable source of validation data as well as hydrodynamic information. Such models can be tuned to respond to differing the patient physiologies. Experimental set-ups can also be compatible with visualization techniques, like particle image velocimetry and cardiovascular magnetic resonance, further adding to the knowledge of the local fluid dynamics. Multi-scale computational models include detailed three-dimensional (3D) anatomical information coupled to a lumped parameter network representing the remainder of the circulation. These models output both overall hemodynamic parameters while also enabling to investigate the local fluid dynamics of the aortic arch or the shunt. As an alternative, pure lumped parameter models can also be employed to model Stage 1 palliation, taking advantage of a much lower computational cost, albeit missing the 3D anatomical component. Finally, analytical techniques, such as wave intensity analysis, can be employed to study the Norwood physiology, providing a mechanistic

  16. Modeling Single Ventricle Physiology: Review of Engineering Tools to Study First Stage Palliation of Hypoplastic Left Heart Syndrome

    PubMed Central

    Biglino, Giovanni; Giardini, Alessandro; Hsia, Tain-Yen; Figliola, Richard; Taylor, Andrew M.; Schievano, Silvia

    2013-01-01

    First stage palliation of hypoplastic left heart syndrome, i.e., the Norwood operation, results in a complex physiological arrangement, involving different shunting options (modified Blalock-Taussig, RV-PA conduit, central shunt from the ascending aorta) and enlargement of the hypoplastic ascending aorta. Engineering techniques, both computational and experimental, can aid in the understanding of the Norwood physiology and their correct implementation can potentially lead to refinement of the decision-making process, by means of patient-specific simulations. This paper presents some of the available tools that can corroborate clinical evidence by providing detailed insight into the fluid dynamics of the Norwood circulation as well as alternative surgical scenarios (i.e., virtual surgery). Patient-specific anatomies can be manufactured by means of rapid prototyping and such models can be inserted in experimental set-ups (mock circulatory loops) that can provide a valuable source of validation data as well as hydrodynamic information. Such models can be tuned to respond to differing the patient physiologies. Experimental set-ups can also be compatible with visualization techniques, like particle image velocimetry and cardiovascular magnetic resonance, further adding to the knowledge of the local fluid dynamics. Multi-scale computational models include detailed three-dimensional (3D) anatomical information coupled to a lumped parameter network representing the remainder of the circulation. These models output both overall hemodynamic parameters while also enabling to investigate the local fluid dynamics of the aortic arch or the shunt. As an alternative, pure lumped parameter models can also be employed to model Stage 1 palliation, taking advantage of a much lower computational cost, albeit missing the 3D anatomical component. Finally, analytical techniques, such as wave intensity analysis, can be employed to study the Norwood physiology, providing a mechanistic

  17. Lung maturity in esophageal atresia: Experimental and clinical study.

    PubMed

    Fragoso, Ana Catarina; Martinez, Leopoldo; Estevão-Costa, José; Tovar, Juan A

    2015-08-01

    Esophageal atresia and tracheoesophageal fistula (EA-TEF) survivors suffer respiratory morbidity of unclear pathogenesis. Defective lung morphogenesis has been described in the rat model. This study examined fetal lung growth and maturity in rats and patients with EA-TEF. Pregnant rats received either adriamycin or vehicle. Control and adriamycin-exposed lungs, with and without EA-TEF, were weighed and processed for RT-PCR, DNA quantification, immunofluorescence and immunoblot analysis of TTF1, VEGF, Sp-B, and α-sma. Twenty human lungs were also processed for immunofluorescence and Alcian-blue staining. Lungs from fetuses with EA-TEF (E21) showed decreased total DNA; FGF7 and TTF1 mRNA expressions were upregulated at E15 and E18, respectively. Protein expression and immunofluorescent distribution of maturity markers were similar. Lungs from stillborns with EA-TEF showed decreased epithelial expression of Sp-B and VEGF whereas those from newborns tended to have less Sp-B and more VEGF and mucous glands. The lungs of rats with EA-TEF were hypoplastic but achieved near-normal maturity. Stillborns with EA-TEF exhibited an apparently disturbed differentiation of the airway epithelium. Newborns with EA-TEF demonstrated subtle differences in the expression of differentiation markers, and increased number of mucous glands that could influence postnatal respiratory adaptation and explain some respiratory symptoms of EA-TEF survivors. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Lung Transplantation

    MedlinePlus

    ... who have severe COPD Cystic fibrosis Idiopathic pulmonary fibrosis Alpha-1 antitrypsin deficiency Pulmonary hypertension Complications of lung transplantation include rejection of the transplanted lung and infection. NIH: National Heart, Lung, and Blood Institute

  19. Lung disease

    MedlinePlus

    ... the lungs to take in oxygen and release carbon dioxide. People with this type of lung disorder often ... the lungs to take up oxygen and release carbon dioxide. These diseases may also affect heart function. An ...

  20. Collapsed Lung

    MedlinePlus

    A collapsed lung happens when air enters the pleural space, the area between the lung and the chest wall. If it is a ... is called pneumothorax. If only part of the lung is affected, it is called atelectasis. Causes of ...

  1. Intrauterine growth retardation, duodenal and extrahepatic biliary atresia, hypoplastic pancreas and other intestinal anomalies: further evidence of the Martínez-Frías syndrome.

    PubMed

    Galán-Gómez, Enrique; Sánchez, Emilio Blesa; Arias-Castro, Sonia; Cardesa-García, Juan J

    2007-01-01

    We describe a patient born to consanguineous parents, who presented with an MCA pattern characterized by low birth weight, duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas and intestinal malrotation. The infant died 60 days after birth. Chromosomes at 550-600 band levels were normal for a female (46,XX). This patient confirmed the autosomal recessive disorder previously described by our group. The pathogenesis of this syndrome is most probably of blastogenetic origin mainly affecting midline developmental duodenal biliary pancreatic junction.

  2. Reduced ascending aorta distensibility relates to adverse ventricular mechanics in patients with hypoplastic left heart syndrome: noninvasive study using wave intensity analysis.

    PubMed

    Biglino, Giovanni; Schievano, Silvia; Steeden, Jennifer A; Ntsinjana, Hopewell; Baker, Catriona; Khambadkone, Sachin; de Leval, Marc R; Hsia, Tain-Yen; Taylor, Andrew M; Giardini, Alessandro

    2012-12-01

    To evaluate the aortic arch elastic properties and ventriculoarterial coupling efficiency in patients with single ventricle physiology, with and without a surgically reconstructed arch. We studied 21 children with single ventricle physiology after bidirectional superior cavopulmonary surgery: 10 with hypoplastic left heart syndrome, who underwent surgical arch reconstruction, and 11 with other types of single ventricle physiology but without arch reconstruction. All children underwent pre-Fontan magnetic resonance imaging. No patient exhibited aortic recoarctation. Data on aortic wave speed, aortic distensibility and wave intensity profiles were all extracted from the magnetic resonance imaging studies using an in-house-written plug-in for the Digital Imaging and Communications in Medicine viewer OsiriX. Children with hypoplastic left heart syndrome had significantly greater wave speed (P = .002), and both stiffer (P = .004) and larger (P < .0001) ascending aortas than the patients with a nonreconstructed arch. Aortic distensibility was not influenced by ventricular stroke volume but depended on a combination of increased aortic diameter and abnormal wall mechanical properties. Those with hypoplastic left heart syndrome had a lower peak wave intensity and reduced energy carried by the forward compression and the forward expansion waves, even after correction for stroke volume, suggesting an abnormal systolic and diastolic function. Lower wave energy was associated with an increased aortic diameter. Using a novel, noninvasive technique based on image analysis, we have demonstrated that aortic arch reconstruction in children with hypoplastic left heart syndrome is associated with reduced aortic distensibility and unfavorable ventricular-vascular coupling compared with those with single ventricle physiology without aortic arch reconstruction. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  3. Brachycephaly, cutis aplasia congenita, blue sclerae, hypertelorism, polydactyly, hypoplastic nipples, failure to thrive, and developmental delay: a distinct autosomal recessive syndrome?

    PubMed

    Teebi, A S; Druker, H A

    2001-01-01

    We report a 6-year-old male of first cousin parents with the unique constellation of frontal bossing with brachycephaly, cutis aplasia congenita, blue sclerae, hypertelorism, hypoplastic nipples, rudimentary unilateral post-axial polydactyly of the hand, failure to thrive, mild to moderate developmental delay and sociable personality. Knoblock-Layer syndrome and Smith-Lemli-Opitz syndrome were considered in the differential diagnosis and were excluded. No similar cases were found in LDDB or other databases.

  4. Evaluation of cardiac function during laparoscopic gastrostomy in pediatric patients with hypoplastic left heart syndrome using intraoperative transesophageal echocardiography.

    PubMed

    Knott, E Marty; Fraser, Jason D; Alemayahu, Hanna; Drake, William B; St Peter, Shawn D; Perryman, Kathy M; Juang, David

    2014-10-01

    Patients with single ventricle physiology (SVP)--specifically, hypoplastic left heart syndrome (HLHS)--frequently need long-term enteral access; however, they are at an extremely high operative risk. Nothing has been published on the physiologic impact on single ventricle function during laparoscopy in this patient population. Therefore, we performed intraoperative transesophageal echocardiography (TEE) to study the physiologic effects of laparoscopic surgery in these patients. After Internal Review Board approval, patients with SVP undergoing laparoscopic gastrostomy were studied with intraoperative TEE, and fractional shortening was determined. Patients were separated into those with HLHS and others with SVP. Data are reported as mean ± standard deviation values. Analysis of variance was used for continuous variables. From August 2011 to February 2013, in total, 11 patients with SVP underwent laparoscopic gastrostomy, including 6 with HLHS. One of the 6 HLHS patients and 1 of the SVP patients underwent concurrent fundoplication. All patients were post-first-stage palliation; two had completed post-second stage. Fractional shortening tended to decrease during insufflation and return to baseline after desufflation. There was no 30-day mortality. Pneumoperitoneum associated with laparoscopic gastrostomy tube placement results in a reversible decrease in fractional shortening in patients with HLHS and SVP. Overall, the children tolerated pneumoperitoneum. TEE allows for real-time assessment of ventricular function and volume and may improve safety during longer procedures.

  5. Quantitative volumetric analysis of a retinoic acid induced hypoplastic model of chick thymus, using Image-J.

    PubMed

    Haque, Ayesha; Khan, Muhammad Yunus

    2017-09-01

    To assess the total volume change in a retinoic acid-induced, hypoplastic model of a chick thymus using Image-J. This experimental study was carried out at the anatomy department of College of Physicians and Surgeons, Islamabad, Pakistan, from February 2009 to February 2010, and comprised fertilised chicken eggs. The eggs were divided into experimental group A and control group C. Group A was injected with 0.3µg of retinoic acid via yolk sac to induce a defective model of a thymus with hypoplasia. The chicks were sacrificed on embryonic day 15 and at hatching. The thymus of each animal was processed, serially sectioned and stained. The total area of each section of thymus was calculated using Image-J. This total area was summed and multiplied with the thickness of each section to obtain volume. Of the 120 eggs, there were 60(50%) in each group. Image analysis revealed a highly significant decrease in the volume of the chick thymus in the experimental group A than its matched control at the time of hatching (p=0.001). Moreover, volumetric depletion progressed with time, being substantially pronounced at hatching compared to the embryonic stage. The volume changes were significant and were effectively quantified using Image-J.

  6. Patient-specific biomechanical model of hypoplastic left heart to predict post-operative cardio-circulatory behaviour.

    PubMed

    Cutrì, Elena; Meoli, Alessio; Dubini, Gabriele; Migliavacca, Francesco; Hsia, Tain-Yen; Pennati, Giancarlo

    2017-09-01

    Hypoplastic left heart syndrome is a complex congenital heart disease characterised by the underdevelopment of the left ventricle normally treated with a three-stage surgical repair. In this study, a multiscale closed-loop cardio-circulatory model is created to reproduce the pre-operative condition of a patient suffering from such pathology and virtual surgery is performed. Firstly, cardio-circulatory parameters are estimated using a fully closed-loop cardio-circulatory lumped parameter model. Secondly, a 3D standalone FEA model is build up to obtain active and passive ventricular characteristics and unloaded reference state. Lastly, the 3D model of the single ventricle is coupled to the lumped parameter model of the circulation obtaining a multiscale closed-loop pre-operative model. Lacking any information on the fibre orientation, two cases were simulated: (i) fibre distributed as in the physiological right ventricle and (ii) fibre as in the physiological left ventricle. Once the pre-operative condition is satisfactorily simulated for the two cases, virtual surgery is performed. The post-operative results in the two cases highlighted similar hemodynamic behaviour but different local mechanics. This finding suggests that the knowledge of the patient-specific fibre arrangement is important to correctly estimate the single ventricle's working condition and consequently can be valuable to support clinical decision. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  7. Application of Mathematical Modeling for Simulation and Analysis of Hypoplastic Left Heart Syndrome (HLHS) in Pre- and Postsurgery Conditions

    PubMed Central

    Jalali, Ali; Jones, Gerard F.; Licht, Daniel J.; Nataraj, C.

    2015-01-01

    This paper is concerned with the mathematical modeling of a severe and common congenital defect called hypoplastic left heart syndrome (HLHS). Surgical approaches are utilized for palliating this heart condition; however, a brain white matter injury called periventricular leukomalacia (PVL) occurs with high prevalence at or around the time of surgery, the exact cause of which is not known presently. Our main goal in this paper is to study the hemodynamic conditions under which HLHS physiology may lead to the occurrence of PVL. A lumped parameter model of the HLHS circulation has been developed integrating diffusion modeling of oxygen and carbon dioxide concentrations in order to study hemodynamic variables such as pressure, flow, and blood gas concentration. Results presented include calculations of blood pressures and flow rates in different parts of the circulation. Simulations also show changes in the ratio of pulmonary to systemic blood flow rates when the sizes of the patent ductus arteriosus and atrial septal defect are varied. These changes lead to unbalanced blood circulations and, when combined with low oxygen and carbon dioxide concentrations in arteries, result in poor oxygen delivery to the brain. We stipulate that PVL occurs as a consequence. PMID:26601113

  8. Chromosomal Abnormalities Affect the Surgical Outcome in Infants with Hypoplastic Left Heart Syndrome: A Large Cohort Analysis.

    PubMed

    Zakaria, Dala; Tang, Xinyu; Bhakta, Rupal; ElHassan, Nahed O; Prodhan, Parthak

    2017-09-18

    Patients with hypoplastic left heart syndrome (HLHS) can have associated genetic abnormalities. This study evaluated the incidence of genetic abnormalities among infants with HLHS and the short-term outcomes of this population during the first hospitalization. This is a retrospective analysis of the multi-center Pediatric Heath Information System database of infants with HLHS who underwent Stage I Norwood, Hybrid, or heart transplant during their first hospitalization from 2004 through 2013. We compared clinical data between infants with and without genetic abnormality, among the three most common chromosomal abnormalities, and between survivors and non-survivors. Multivariable analysis was completed to evaluate predictors of mortality among patients with genetic abnormalities. A total of 5721 infants with HLHS were identified; 282 (5%) had associated genetic abnormalities. The three most common chromosomal abnormalities were Turner (25%), DiGeorge (22%), and Downs (12.7%) syndromes. Over the study period, the number of patients with genetic abnormalities undergoing cardiac operations increased without any significant increases in mortality. Infants with genetic abnormalities compared to those without abnormalities had longer hospital length of stay and higher morbidity and mortality. Variables associated with mortality were lower gestational age, longer duration of vasopressor therapy, need for dialysis, and cardiopulmonary resuscitation; and complicated clinical course as suggested by necrotizing enterocolitis, septicemia. Presence of any genetic abnormality in infants with HLHS undergoing cardiac surgery is associated with increased mortality and morbidity. Timely genetic testing, appropriate family counseling, and thorough preoperative case selection are suggested for these patients for any operative intervention.

  9. Array-CGH and quantitative PCR genetic analysis in a case with bilateral hypoplasia of pulmonary arteries and lungs and simultaneous unilateral renal agenesis.

    PubMed

    Hussein, Kais; Steinemann, Doris; Scholz, Henrike; Menkhaus, Ralf; Feist, Henning; Kreipe, Hans

    2010-08-18

    We describe the clinical course and have characterised anatomically and genetically a unique case of a newborn with bilateral hypoplasia of pulmonary arteries, consecutive extremely hypoplastic lung tissue and associated unilateral renal agenesis. Intrauterine oxygenation by the placenta seemed to have allowed normotrophic body maturity but immediately after delivery, in the third trimester, progressive hypoxemia developed and the newborn succumbed to acute respiratory failure. Genetic analysis by array-based comparative genomic hybridisation and quantitative PCR revealed duplication of 1p21, which, however, might not be the disease causing aberration. This case might represent an extreme form of previously reported, rare cases with simultaneous dysorganogenesis of lungs and kidneys.

  10. Wnt7b stimulates embryonic lung growth by coordinately increasing the replication of epithelium and mesenchyme.

    PubMed

    Rajagopal, Jayaraj; Carroll, Thomas J; Guseh, J Sawalla; Bores, Sam A; Blank, Leah J; Anderson, William J; Yu, Jing; Zhou, Qiao; McMahon, Andrew P; Melton, Douglas A

    2008-05-01

    The effects of Wnt7b on lung development were examined using a conditional Wnt7b-null mouse. Wnt7b-null lungs are markedly hypoplastic, yet display largely normal patterning and cell differentiation. In contrast to findings in prior hypomorphic Wnt7b models, we find decreased replication of both developing epithelium and mesenchyme, without abnormalities of vascular smooth muscle development. We further demonstrate that Wnt7b signals to neighboring cells to activate both autocrine and paracrine canonical Wnt signaling cascades. In contrast to results from hypomorphic models, we show that Wnt7b modulates several important signaling pathways in the lung. Together, these cascades result in the coordinated proliferation of adjacent epithelial and mesenchymal cells to stimulate organ growth with few alterations in differentiation and patterning.

  11. Management Options and Outcomes for Neonatal Hypoplastic Left Heart Syndrome in the Early Twenty-First Century.

    PubMed

    Kane, Jason M; Canar, Jeff; Kalinowski, Valerie; Johnson, Tricia J; Hoehn, K Sarah

    2016-02-01

    Without surgical treatment, neonatal hypoplastic left heart syndrome (HLHS) mortality in the first year of life exceeds 90 % and, in spite of improved surgical outcomes, many families still opt for non-surgical management. The purpose of this study was to investigate trends in neonatal HLHS management and to identify characteristics of patients who did not undergo surgical palliation. Neonates with HLHS were identified from a serial cross-sectional analysis using the Healthcare Cost and Utilization Project's Kids' Inpatient Database from 2000 to 2012. The primary analysis compared children undergoing surgical palliation to those discharged alive without surgery using a binary logistic regression model. Multivariate logistic regression was conducted to determine factors associated with treatment choice. A total of 1750 patients underwent analysis. Overall hospital mortality decreased from 35.3 % in 2000 to 22.9 % in 2012. The percentage of patients undergoing comfort care discharge without surgery also decreased from 21.2 to 14.8 %. After controlling for demographics and comorbidities, older patients at presentation were less likely to undergo surgery (OR 0.93, 0.91-0.96), and patients in 2012 were more likely to undergo surgery compared to those in prior years (OR 1.5, 1.1-2.1). Discharge without surgical intervention is decreasing with a 30 % reduction between 2000 and 2012. Given the improvement in surgical outcomes, further dialogue about ethical justification of non-operative comfort or palliative care is warranted. In the meantime, clinicians should present families with surgical outcome data and recommend intervention, while supporting their option to refuse.

  12. Computational models of aortic coarctation in hypoplastic left heart syndrome: considerations on validation of a detailed 3D model.

    PubMed

    Biglino, Giovanni; Corsini, Chiara; Schievano, Silvia; Dubini, Gabriele; Giardini, Alessandro; Hsia, Tain-Yen; Pennati, Giancarlo; Taylor, Andrew M

    2014-05-01

    Reliability of computational models for cardiovascular investigations strongly depends on their validation against physical data. This study aims to experimentally validate a computational model of complex congenital heart disease (i.e., surgically palliated hypoplastic left heart syndrome with aortic coarctation) thus demonstrating that hemodynamic information can be reliably extrapolated from the model for clinically meaningful investigations. A patient-specific aortic arch model was tested in a mock circulatory system and the same flow conditions were re-created in silico, by setting an appropriate lumped parameter network (LPN) attached to the same three-dimensional (3D) aortic model (i.e., multi-scale approach). The model included a modified Blalock-Taussig shunt and coarctation of the aorta. Different flow regimes were tested as well as the impact of uncertainty in viscosity. Computational flow and pressure results were in good agreement with the experimental signals, both qualitatively, in terms of the shape of the waveforms, and quantitatively (mean aortic pressure 62.3 vs. 65.1 mmHg, 4.8% difference; mean aortic flow 28.0 vs. 28.4% inlet flow, 1.4% difference; coarctation pressure drop 30.0 vs. 33.5 mmHg, 10.4% difference), proving the reliability of the numerical approach. It was observed that substantial changes in fluid viscosity or using a turbulent model in the numerical simulations did not significantly affect flows and pressures of the investigated physiology. Results highlighted how the non-linear fluid dynamic phenomena occurring in vitro must be properly described to ensure satisfactory agreement. This study presents methodological considerations for using experimental data to preliminarily set up a computational model, and then simulate a complex congenital physiology using a multi-scale approach.

  13. Energy loss and coronary flow simulation following hybrid stage I palliation: a hypoplastic left heart computational fluid dynamic model

    PubMed Central

    Shuhaiber, Jeffrey H.; Niehaus, Justin; Gottliebson, William; Abdallah, Shaaban

    2013-01-01

    OBJECTIVES The theoretical differences in energy losses as well as coronary flow with different band sizes for branch pulmonary arteries (PA) in hypoplastic left heart syndrome (HLHS) remain unknown. Our objective was to develop a computational fluid dynamic model (CFD) to determine the energy losses and pulmonary-to-systemic flow rates. This study was done for three different PA band sizes. METHODS Three-dimensional computer models of the hybrid procedure were constructed using the standard commercial CFD softwares Fluent and Gambit. The computer models were controlled for bilateral PA reduction to 25% (restrictive), 50% (intermediate) and 75% (loose) of the native branch pulmonary artery diameter. Velocity and pressure data were calculated throughout the heart geometry using the finite volume numerical method. Coronary flow was measured simultaneously with each model. Wall shear stress and the ratio of pulmonary-to-systemic volume flow rates were calculated. Computer simulations were compared at fixed points utilizing echocardiographic and catheter-based metric dimensions. RESULTS Restricting the PA band to a 25% diameter demonstrated the greatest energy loss. The 25% banding model produced an energy loss of 16.76% systolic and 24.91% diastolic vs loose banding at 7.36% systolic and 17.90% diastolic. Also, restrictive PA bands had greater coronary flow compared with loose PA bands (50.2 vs 41.9 ml/min). Shear stress ranged from 3.75 Pascals with restrictive PA banding to 2.84 Pascals with loose banding. Intermediate PA banding at 50% diameter achieved a Qp/Qs (closest to 1) at 1.46 systolic and 0.66 diastolic compared with loose or restrictive banding without excess energy loss. CONCLUSIONS CFD provides a unique platform to simulate pressure, shear stress as well as energy losses of the hybrid procedure. PA banding at 50% provided a balanced pulmonary and systemic circulation with adequate coronary flow but without extra energy losses incurred. PMID:23660734

  14. Mechanisms of tricuspid valve regurgitation in hypoplastic left heart syndrome: a case-matched echocardiographic-surgical comparison study.

    PubMed

    Bharucha, Tara; Honjo, Osami; Seller, Neil; Atlin, Cori; Redington, Andrew; Caldarone, Christopher A; van Arsdell, Glen; Mertens, Luc

    2013-02-01

    The multifactorial mechanisms of tricuspid valve (TV) insufficiency in patients with hypoplastic left heart syndrome (HLHS) include structural anomalies of TV leaflets and ventricular dilatation. We hypothesized that 2-D echocardiography underestimates the importance of TV structural abnormalities, whereas surgical assessment underestimates the importance of motion abnormalities, and compared echocardiographic assessment with surgical description. Two independent experts retrospectively reviewed echocardiograms of all patients who had staged single-ventricular palliation and TV repair during January 1998-December 2008, and compared with case-matched controls who did not require TV repair. Primary and secondary mechanisms of TV insufficiency were categorized, and surgical findings ascertained from operation records. There were 32 patients with a median age of 5.9 months (0.3-140) and 32 matched controls. On echocardiographic review, an abnormality of at least one leaflet was noted in every patient (100%) vs. in only 14 controls 14 (44%) (P < 0.001). Leaflet prolapse was described in 22 (69%), and the restriction of a leaflet in 20 (69%). Agreement between the experts was excellent (κ = 0.64-0.88). On surgical inspection, annular dilatation was found in 17 (53%), and leaflet dysplasia in 14 (44%). Agreement between echocardiographic and surgical assessment was poor (κ < 0.6). Important structural abnormalities are common in patients with HLHS and TV insufficiency, some readily identified by 2-D echocardiography. However, there are significant discrepancies between echocardiographic and surgical findings. Echocardiographic assessment is sensitive to detect leaflet motion abnormalities, but not leaflet structural abnormalities. Both echocardiographers and surgeons should be aware of these limitations when planning surgical interventions.

  15. Assessing ST Segment Changes and Ischemia During Exercise Stress Testing in Patients with Hypoplastic Left Heart Syndrome and Fontan Palliation.

    PubMed

    Kyle, William Buck; Denfield, Susan W; Valdes, Santiago O; Penny, Daniel J; Bolin, Elijah H; Lopez, Keila N

    2016-03-01

    While exercise stress testing (EST) is an important tool, little is known about its use for determining ischemia in patients with hypoplastic left heart syndrome (HLHS) and Fontan palliation. We sought to determine the frequency of ST segment changes during EST in HLHS patients after Fontan and examine results of further testing performed in response to ST changes. A single-center chart review of HLHS patients post-Fontan from January 1995 to December 2012 was performed. Data collected included demographics, indications for EST, resting electrocardiogram findings, EST and echocardiogram results and outcomes. ESTs were evaluated for ST segment changes concerning for ischemia. Results of additional testing performed based on concerning EST findings were collected. Twenty-seven patients underwent 64 ESTs (mean 2.4 ESTs/patient). Median age at first EST was 9.6 years (range 6.2-16.4). EST was concerning for ischemia in 13 patients (48 %) on 25 (39 %) ESTs. Based on EST results, two patients had stress sestamibi testing, two underwent coronary angiography, and one had both. No reversible perfusion defects or coronary artery obstructions were demonstrated. No patient who underwent EST has died. ST segment depression was not associated with ventricular dysfunction prior to EST or at the end of follow-up (p > 0.05). In patients with HLHS post-Fontan palliation, ST segment depression on EST is common. In patients who underwent further testing, no evidence of ischemia or coronary abnormalities was found. Additional testing may not be necessary in all patients.

  16. Is "treat your child normally" helpful advice for parents of survivors of treatment of hypoplastic left heart syndrome?

    PubMed

    Rempel, Gwen R; Harrison, Margaret J; Williamson, Deanna L

    2009-04-01

    Developing technology affords children with complex congenitally malformed hearts a chance for survival. Parents gratefully pursue life-saving options on behalf of their children, despite the risks to the life of their child, and uncertainty about outcomes. Little is known about how mothers and fathers experience parenting a child whose new state as a survivor may include less than optimal developmental sequels. Our study involved multiple interactive interviews with 9 mothers and 7 fathers of infants and preschool children with hypoplastic left heart syndrome who had survived the Norwood surgical approach. Qualitative methodology included grounded theory methods of simultaneous collection and analysis of data, and we used open and selective coding of transcribed interviews. Parents used normalization in the context of uncertainty regarding the ongoing survival of their child. Parents described their underweight children as being on their own growth curve, and viewed their developmental progress, however delayed, as reason for celebration, as they had been prepared for their child to die. There is growing evidence that children with congenitally malformed hearts who require surgical intervention during the first year of life may experience developmental delay. The use of normalization by their parents may be effective in decreasing their worry regarding the uncertain future faced by their child, but may negatively affect the developmental progress of the child if they do not seek resources to assist development. Advice from paediatric specialists for parents to view their children as normal needs to be balanced with assistance for parents to access services to support optimal growth and development of their child.

  17. Venous saturation and the anaerobic threshold in neonates after the Norwood procedure for hypoplastic left heart syndrome.

    PubMed

    Hoffman, G M; Ghanayem, N S; Kampine, J M; Berger, S; Mussatto, K A; Litwin, S B; Tweddell, J S

    2000-11-01

    Reduction in oxygen delivery can lead to organ dysfunction and death by cellular hypoxia, detectable by progressive (mixed) venous oxyhemoglobin desaturation until extraction is limited at the anaerobic threshold. We sought to determine the critical level of venous oxygen saturation to maintain aerobic metabolism in neonates after the Norwood procedure (NP) for the hypoplastic left heart syndrome (HLHS). A prospective perioperative database was maintained for demographic, hemodynamic, and laboratory data. Invasive arterial and atrial pressures, arterial saturation, oximetric superior vena cava (SVC) saturation, and end-tidal CO2 were continuously recorded and logged hourly for the first 48 postoperative hours. Arterial and venous blood gases and cooximetry were obtained at clinically appropriate intervals. SVC saturation was used as an approximation of mixed venous saturation (SvO2). A standard base excess (BE) less than -4 mEq/L (BElo), or a change exceeding -2 mEq/L/h (deltaBElo), were used as indicators of anaerobic metabolism. The relationship between SvO2 and BE was tested by analysis of variance and covariance for repeated measures; the binomial risk of BElo or deltaBElo at SvO2 strata was tested by the likelihood ratio test and logistic regression, with cutoff at p < 0.05. Complete data were available in 48 of 51 consecutive patients undergoing NP yielding 2,074 valid separate determinations. BE was strongly related to SvO2 (model R2 = 0.40, p < 0.0001) with minimal change after adjustment for physiologic covariates. The risk of anaerobic metabolism was 4.8% overall, but rose to 29% when SvO2 was 30% or below (p < 0.0001). Survival was 100% at 1 week and 94% at hospital discharge. Analysis of acid-base changes revealed an apparent anaerobic threshold when SvO2 fell below 30%. Clinical management to maintain SvO2 above this threshold yielded low mortality.

  18. Hypoplastic Left Heart Syndrome Links to Chromosomes 10q and 6q and Is Genetically Related to Bicuspid Aortic Valve

    PubMed Central

    Hinton, Robert B.; Martin, Lisa J.; Rame-Gowda, Smitha; Tabangin, Meredith E.; Cripe, Linda H.; Benson, D. Woodrow

    2009-01-01

    Objectives This study was designed to identify disease loci for hypoplastic left heart syndrome (HLHS) and evaluate the genetic relationship between HLHS and bicuspid aortic valve (BAV). Background Previously, we identified that HLHS and BAV exhibit complex inheritance, and both HLHS and BAV kindreds are enriched for BAV. However, the genetic basis of HLHS and its relationship to BAV remains unclear. Methods Family-based nonparametric genome-wide linkage analysis was performed in kindreds ascertained by either an HLHS or BAV proband. Echocardiograms were performed on 1,013 participants using a sequential sampling strategy (33 HLHS kindreds, 102 BAV kindreds). Results The recurrence risk ratio of BAV in HLHS families (8.05) was nearly identical to that in BAV families (8.77). Linkage to chromosomal regions 10q22 and 6q23 with maximum logarithm of odds scores of 3.2 and 3.1, respectively, was identified in HLHS kindreds. In addition, 5 suggestive loci were identified (7q31, 11q22, 12q13, 14q23, and 20q11). We previously identified loci at chromosomes 18q22, 13q34, and 5q21 in BAV kindreds. The relationship between these loci was examined in the combined HLHS and BAV cohort and associations between loci were demonstrated (5q21, 13q34, and 14q23; 6q23 and 10q22; 7q31 and 20q11). Subsequent subsets linkage analysis showed a significant improvement in the logarithm of odds score at 14q23 only (4.1, p < 0.0001). Conclusions These studies demonstrate linkage to multiple loci identifying HLHS as genetically heterogeneous. Subsets linkage analyses and recurrence risk ratios in a combined cohort provide evidence that some HLHS and BAV are genetically related. PMID:19298921

  19. Potential Molecular Mechanism of Retrograde Aortic Arch Stenosis in the Hybrid Approach to Hypoplastic Left Heart Syndrome

    PubMed Central

    Hibino, Narutoshi; Cismowski, Mary J.; Lilly, Brenda J.; McConnell, Patrick I.; Shinoka, Toshiharu; Cheatham, John P.; Lucchesi, Pamela A.; Galantowicz, Mark E.; Trask, Aaron J.

    2015-01-01

    Background The hybrid palliation for hypoplastic left heart syndrome (HLHS) has emerged as an alternative approach to the Norwood procedure. The development of patent ductus arteriosus (PDA) in-stent stenosis can cause retrograde aortic arch stenosis (RAAS), leading to significant morbidity. This study aimed to identify potential mechanisms of PDA in-stent stenosis contributing to RAAS. METHODS Tissues from stented PDA were collected from 17 patients undergoing comprehensive stage 2 repair between 2009 and 2014. Patients requiring RAAS intervention based on cardiology–surgery consensus were defined as RAAS (+) (n=10), whereas patients without any RAAS intervention were defined as RAAS (−) (n=7). Tissues were examined by qPCR analysis for vascular smooth muscle cell (VSMC) differentiation and proliferation markers. RESULTS Patient characteristics were: HLHS with aortic atresia: 6; HLHS with aortic stenosis: 3; unbalanced AVC: 3; DILV/TGA: 3; DORV: 2. VSMC differentiation markers (β–actin, SM22, and calponin) and signaling pathways for VSMC modulation (TGFβ1, Notch, and PDGF-BB) were significantly higher in the RAAS (+) than in RAAS (−). The proliferation marker Ki67 was increased in RAAS (+). Cell cycle markers were comparable in both groups. CONCLUSION Increased VSMC differentiation and proliferation markers suggest a mechanism for inward neointima formation of the PDA in RAAS. The apparent lack of change in cell cycle markers is contrary to coronary artery in-stent stenosis, suggesting further targets should be examined. Combined primary in vitro PDA cell culture and proteomics can be strong tools to elucidate targets to reduce PDA in-stent stenosis for RAAS in the future. PMID:26163359

  20. Energy loss and coronary flow simulation following hybrid stage I palliation: a hypoplastic left heart computational fluid dynamic model.

    PubMed

    Shuhaiber, Jeffrey H; Niehaus, Justin; Gottliebson, William; Abdallah, Shaaban

    2013-08-01

    The theoretical differences in energy losses as well as coronary flow with different band sizes for branch pulmonary arteries (PA) in hypoplastic left heart syndrome (HLHS) remain unknown. Our objective was to develop a computational fluid dynamic model (CFD) to determine the energy losses and pulmonary-to-systemic flow rates. This study was done for three different PA band sizes. Three-dimensional computer models of the hybrid procedure were constructed using the standard commercial CFD softwares Fluent and Gambit. The computer models were controlled for bilateral PA reduction to 25% (restrictive), 50% (intermediate) and 75% (loose) of the native branch pulmonary artery diameter. Velocity and pressure data were calculated throughout the heart geometry using the finite volume numerical method. Coronary flow was measured simultaneously with each model. Wall shear stress and the ratio of pulmonary-to-systemic volume flow rates were calculated. Computer simulations were compared at fixed points utilizing echocardiographic and catheter-based metric dimensions. Restricting the PA band to a 25% diameter demonstrated the greatest energy loss. The 25% banding model produced an energy loss of 16.76% systolic and 24.91% diastolic vs loose banding at 7.36% systolic and 17.90% diastolic. Also, restrictive PA bands had greater coronary flow compared with loose PA bands (50.2 vs 41.9 ml/min). Shear stress ranged from 3.75 Pascals with restrictive PA banding to 2.84 Pascals with loose banding. Intermediate PA banding at 50% diameter achieved a Qp/Qs (closest to 1) at 1.46 systolic and 0.66 diastolic compared with loose or restrictive banding without excess energy loss. CFD provides a unique platform to simulate pressure, shear stress as well as energy losses of the hybrid procedure. PA banding at 50% provided a balanced pulmonary and systemic circulation with adequate coronary flow but without extra energy losses incurred.

  1. Lung transplant

    MedlinePlus

    ... diseases that may require a lung transplant are: Cystic fibrosis Damage to the arteries of the lung because ... BC; Clinical Practice Guidelines for Pulmonary Therapies Committee; ... Therapies Committee. Cystic fibrosis pulmonary guidelines: ...

  2. Paracentric inversion of chromosome 7 (46,XX,inv(7)(q21.2q22)) in a newborn with hypoplastic left heart syndrome

    SciTech Connect

    Kuforjii, T.A.; Pillers, D.M.; Silberbach, M.

    1994-09-01

    Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease that is uniformly fatal without surgical intervention. Fetal echocardiography allows prenatal diagnosis, but this condition may not become apparent until after the mid-second trimester. We report a term baby with severe HLHS who had an 18 week fetal ultrasound that reportedly demonstrated a normal heart. There was no family history of congenital heart disease. She was phenotypically female with no dysmorphic features. Physical examination was otherwise normal. She expired at 48 hours of age. The autopsy was noncontributory. The karyotype was 46,XX, but there was an apparently balanced paracentric inversion of the long arm of chromosome 7 (46,XX,inv(7)(q21.2q22)). The mother`s chromosome study was normal without any inversion, and the father was not available for study. Hypoplastic left heart syndrome has been associated with extracardiac anomalies and chromosomal abnormalities including 45,XO,11q-, and trisomy 18. It has also been reported in 5 members spanning 3 generations of a family with a spectrum of left heart defects suggesting an autosomal dominant pattern with high penetrance. First-degree relatives of infants with HLHS have a thirteen percent incidence of related cardiovascular malformations, a frequency higher than predicted by a multifactorial model of inheritance, suggesting that at least a portion of HLHS have a genetic basis. Karyotype analysis, including high resolution banding, may help define the etiology of this condition. Chromosome 7 has not been implicated in HLHS. This case emphasizes the need for genetic analysis, including a pedigree, of affected families. It also underscores the importance of screening by karyotype analysis to determine whether defects of the long arm of chromosome 7 are important in the pathogenesis of hypoplastic left heart syndrome.

  3. Surgical management of a hypoplastic distal aortic arch and coarctation of aorta in a patient with Klippel-Feil syndrome, ascending aortic aneurysm and bicuspid aortic valve.

    PubMed

    Sabol, Frantisek; Kolesar, Adrián; Toporcer, Tomás; Bajmoczi, Milan

    2014-10-01

    Klippel-Feil syndrome has been associated with cardiovascular malformations, but only 3 cases have been reported to be associated with aortic coarctation and surgical management is not defined. A 51-year old woman with Klippel-Feil syndrome associated with an aneurysm of the ascending aorta, hypoplastic aortic arch and aortic coarctation at the level of the left subclavian artery presented with shortness of breath 2 years after diagnosis. Imaging identified interim development of a 7.2-cm aneurysm at the level of the aortic coarctation. She underwent surgical repair with a Dacron interposition graft under hypothermic circulatory arrest. She continues to do well 18 months following repair.

  4. Two problems and a single solution: Covered stent implantation to close an anterograde pulmonary flow and treat hypoplastic left pulmonary artery after Fontan operation.

    PubMed

    Butera, Gianfranco; Taha, Fatma

    2016-05-01

    Several issues may impact on the function of a Fontan circulation including accessory source of pulmonary blood flow and pulmonary artery anatomy. Here we report on a 5.5-year-old boy who showed failing Fontan circulation due to left pulmonary artery stenosis/hypoplasia and significant forward pulmonary blood flow through the native pulmonary artery. Successful implantation of a 34-mm CP covered stent in the left pulmonary artery in a Fontan patient was useful for simultaneous successful treatment of residual antegrade flow from the systemic ventricle to the pulmonary artery and enlargement of hypoplastic left pulmonary artery. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  5. Lung Organogenesis

    PubMed Central

    Warburton, David; El-Hashash, Ahmed; Carraro, Gianni; Tiozzo, Caterina; Sala, Frederic; Rogers, Orquidea; De Langhe, Stijn; Kemp, Paul J.; Riccardi, Daniela; Torday, John; Bellusci, Saverio; Shi, Wei; Lubkin, Sharon R; Jesudason, Edwin

    2011-01-01

    Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the “molecular embryology” of the lung was first comprehensively reviewed, new challenges have emerged—and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits. PMID:20691848

  6. Prenatal diagnosis of hypoplastic left heart syndrome: impact of counseling patterns on parental perceptions and decisions regarding termination of pregnancy.

    PubMed

    Hilton-Kamm, Debra; Chang, Ruey-Kang; Sklansky, Mark

    2012-12-01

    An online survey for parents of children with congenital heart disease (CHD) was developed to study parents' experiences at the time of diagnosis. The survey was distributed to online support groups. A total of 841 responses from parents of children with CHD were received during a 4-week period. The current study examined those respondents (211 [25 %]) who reported their child's diagnosis as hypoplastic left heart syndrome (HLHS). Among these, 138 (65 %) reported receiving the diagnosis prenatally. 32 % of those receiving a prenatal diagnosis reported that after they declined to terminate the pregnancy, termination was mentioned again by their physicians. Parents who had termination mentioned again after their initial decline reported significantly lower optimism regarding their child's life expectancy than those who did not have it mentioned again (66 vs. 94 %, p < 0.001); were more likely to interpret the term "rare" to mean "little or no chance of survival" (34 vs. 13 %, p = 0.01); and were more likely to change pediatric cardiologists (PCs) (43 vs. 12 %, p < 0.001). Similarly, 22 % of respondents receiving a prenatal diagnosis reported feeling pressure to terminate the pregnancy by the PC. Those who felt pressure to terminate reported lower optimism about their child's life expectancy than respondents who did not feel pressure (48 vs. 88 %, p < 0.001) and were more likely to choose a new PC (48 vs. 17 %, p < 0.001). In our cohort of parents, when termination of pregnancy was mentioned after the parents declined it, or if the parents felt pressure to terminate, the parents perceived a lower chance of survival, felt less optimistic about their child's life expectancy, and were more likely to choose another PC for long-term follow-up care. Our study could not determine whether repeated discussions of the possibility for termination of pregnancy independently impacts parental optimism regarding prognosis or whether those who counsel with repeated discussions of

  7. Neutrophil/Lymphocyte ratio and association with arch intervention in patients with hypoplastic left heart syndrome undergoing hybrid procedure.

    PubMed

    Mitchell, Elizabeth; Cheatham, John P; Sisk, James M; Nicholson, Lisa; Holzer, Ralf; Galantowicz, Mark; Cua, Clifford L

    2014-01-01

    Hybrid procedure is an alternative initial palliation for patients with hypoplastic left heart syndrome (HLHS). One major complication with this procedure is stenosis in the aortic arch isthmus possibly due to inflammation from the patent ductus arteriosus (PDA) stent. In adult studies, neutrophil/lymphocyte (N/L) ratio has been used as a marker for increased inflammation and has been associated with increased risk for coronary artery stent stenosis. The goal of this study was to determine if there were differences in N/L ratio between patients with HLHS undergoing hybrid procedure that required an arch intervention (AI-Group) vs. those that did not require an intervention (NAI-Group). Retrospective chart review was performed on patients with HLHS undergoing hybrid procedure between July 2002 and January 2013. Complete blood counts as well as differentials were recorded at four time periods: 1 day prehybrid palliation, one day posthybrid palliation, 1 week posthybrid palliation, and 3 weeks posthybrid palliation. One hundred six patients were evaluated (AI-Group = 38, NAI-Group = 68). AI-Group generally had a higher N/L ratio vs. NAI-group and this was significant immediately 1 day posthybrid palliation: AI-Group vs. NAI-Group, prehybrid (2.95 ± 2.62 vs. 2.44 ± 1.71), 1 day posthybrid (5.95 ± 4.16 vs. 4.34 ± 3.87, P < .05), 1 week posthybrid (2.72 ± 3.01 vs. 2.28 ± 2.12), and 3 weeks posthybrid (1.85 ± 1.24 vs. 1.45 ± 1.16), respectively. Lymphocyte percentage was significantly lower in the AI-Group vs. NAI-Group 3 weeks posthybrid palliation (33.00 + 11.30% vs. 40.65 + 16.82%). Patients that required an arch intervention after hybrid palliation had a higher N/L ratio immediately after the procedure. This may signify increased inflammatory reaction that places these patients at risk for stenosis. Future studies are needed to determine if N/L ratio is a robust marker to risk stratify patients undergoing the hybrid procedure for arch complications. © 2014

  8. A Novel Null Mutation in P450 Aromatase Gene (CYP19A1) Associated with Development of Hypoplastic Ovaries in Humans

    PubMed Central

    Akçurin, Sema; Türkkahraman, Doğa; Kim, Woo-Young; Durmaz, Erdem; Shin, Jae-Gook; Lee, Su-Jun

    2016-01-01

    Objective: The CYP19A1 gene product aromatase is responsible for estrogen synthesis and androgen/estrogen equilibrium in many tissues, particularly in the placenta and gonads. Aromatase deficiency can cause various clinical phenotypes resulting from excessive androgen accumulation and insufficient estrogen synthesis during the pre- and postnatal periods. In this study, our aim was to determine the clinical characteristics and CYP19A1 mutations in three patients from a large Turkish pedigree. Methods: The cases were the newborns referred to our clinic for clitoromegaly and labial fusion. Virilizing signs such as severe acne formation, voice deepening, and clitoromegaly were noted in the mothers during pregnancy. Preliminary diagnosis was aromatase deficiency. Therefore, direct DNA sequencing of CYP19A1 was performed in samples from parents (n=5) and patients (n=3). Results: In all patients, a novel homozygous insertion mutation in the fifth exon (568insC) was found to cause a frameshift in the open reading frame and to truncate the protein prior to the heme-binding region which is crucial for enzymatic activity. The parents were found to be heterozygous for this mutation. Additionally, all patients had hypoplastic ovaries instead of cystic and enlarged ovaries. Conclusion: A novel 568C insertion mutation in CYP19A1 can lead to severe aromatase deficiency. Homozygosity for this mutation is associated with the development of hypoplastic ovaries. This finding provides an important genetic marker for understanding the physiological function of aromatase in fetal ovarian development. PMID:27086564

  9. Serial changes in anatomy and ventricular function on dual-source cardiac computed tomography after the Norwood procedure for hypoplastic left heart syndrome.

    PubMed

    Goo, Hyun Woo

    2017-09-06

    Accurate evaluation of anatomy and ventricular function after the Norwood procedure in hypoplastic left heart syndrome is important for treatment planning and prognostication, but echocardiography and cardiac MRI have limitations. To assess serial changes in anatomy and ventricular function on dual-source cardiac CT after the Norwood procedure for hypoplastic left heart syndrome. In 14 consecutive patients with hypoplastic left heart syndrome, end-systolic and end-diastolic phase cardiac dual-source CT was performed before and early (average: 1 month) after the Norwood procedure, and repeated late (median: 4.5 months) after the Norwood procedure in six patients. Ventricular functional parameters and indexed morphological measurements including pulmonary artery size, right ventricular free wall thickness, and ascending aorta size on cardiac CT were compared between different time points. Moreover, morphological features including ventricular septal defect, endocardial fibroelastosis and coronary ventricular communication were evaluated on cardiac CT. Right ventricular function and volumes remained unchanged (indexed end-systolic and end-diastolic volumes: 38.9±14.0 vs. 41.1±21.5 ml/m(2), P=0.7 and 99.5±30.5 vs. 105.1±33.0 ml/m(2), P=0.6; ejection fraction: 60.1±7.3 vs. 63.8±7.0%, P=0.1, and indexed stroke volume: 60.7±18.0 vs. 64.0±15.6 ml/m(2), P=0.5) early after the Norwood procedure, but function was decreased (ejection fraction: 64.2±2.6 vs. 58.1±7.1%, P=0.01) and volume was increased (indexed end-systolic and end-diastolic volumes: 39.2±14.9 vs. 68.9±20.6 ml/m(2), P<0.003 and 107.8±36.5 vs. 162.9±36.2 ml/m(2), P<0.006, and indexed stroke volume: 68.6±21.7 vs. 94.0±21.3 ml/m(2), P=0.02) later. Branch pulmonary artery size showed a gradual decrease without asymmetry after the Norwood procedure. Right and left pulmonary artery stenoses were identified in 21.4% (3/14) of the patients. Indexed right ventricular free wall thickness showed a

  10. [The lung].

    PubMed

    Martinod, Emmanuel; Uzunhan, Yurdagül; Radu, Dana M; Seguin, Agathe; Boddaert, Guillaume; Valeyre, Dominique; Planès, Carole; Carpentier, Alain

    2011-10-01

    Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.

  11. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  12. Lung Diseases

    MedlinePlus

    When you breathe, your lungs take in oxygen from the air and deliver it to the bloodstream. The cells in your body need oxygen to ... you breathe nearly 25,000 times. People with lung disease have difficulty breathing. Millions of people in ...

  13. Lung Cancer

    MedlinePlus

    Lung cancer is one of the most common cancers in the world. It is a leading cause of cancer death in men and women in the United States. Cigarette smoking causes most lung cancers. The more cigarettes you smoke per day and ...

  14. What Is Lung Cancer?

    MedlinePlus

    ... Graphics Infographic Stay Informed Cancer Home What Is Lung Cancer? Language: English Español (Spanish) Recommend on Facebook Tweet ... cancer starts in the lungs, it is called lung cancer. Lung cancer begins in the lungs and may ...

  15. Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  16. Lung Cancer Prevention

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Prevention (PDQ®)–Patient Version What is prevention? ... to keep cancer from starting. General Information About Lung Cancer Key Points Lung cancer is a disease ...

  17. Scimitar syndrome: Anaesthetic management for pulmonary resection of the unaffected lung.

    PubMed

    Fernández-Torres, B; Fernández-López, A; Congregado, M

    2017-05-26

    Scimitar syndrome is a rare congenital anomaly characterized by anomalous drainage of the right pulmonary veins in the inferior vena cava, frequently associated with right lung and pulmonary artery hypoplasia, dextrocardia and abnormal systemic arterial supply to the lower lobe. Pulmonary resection surgery on healthy lung is exceptional, and there are no published records of it, as far as we know. A man with scimitar syndrome diagnosed with a lung nodule with malignant features in the contralateral lung. This situation implies huge anaesthetic complexity, mainly for intraoperative ventilation. Although spirometry and stress test did not contraindicate the planned lobectomy, scintigraphy showed a hypoplastic right lung with an uptake of 15%. From an anaesthetic point of view we discarded selective ventilation of the right lung, since the shunt made it functionally non-existent. In consequence we proposed four anaesthetic possibilities. After the placement of an epidural catheter and left selective intubation, thoracoscopy with intermittent apnoeas was our first choice, and we could complete the extirpation and avoid excessive complexity. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Perioperative Management of a Child with Hypoplastic Left Heart Syndrome of the Jehovah's Witness Faith Presenting for Hybrid Comprehensive Stage II Procedure

    PubMed Central

    Karuppiah, Sathappan; Mckee, Christopher; Hodge, Ashley; Galantowicz, Mark; Tobias, Joseph; Naguib, Aymen

    2016-01-01

    Abstract: Over the years, there has been a growing recognition of the potential negative sequelae of allogeneic blood products on postoperative outcomes following cardiac surgery. In addition, followers of the Jehovah's Witness (JW) faith have a religious restriction against receiving blood or blood components. Advances in perioperative care, cardiopulmonary bypass (CPB), and surgical technique have minimized the need for allogeneic blood products. Specific blood conservation strategies include maximizing the preoperative hematocrit and coagulation function as well as intraoperative strategies, such as acute normovolemic hemodilution and adjustments of the technique of CPB. We report a 7-month-old patient whose parents were of the JW faith who underwent a comprehensive stage II procedure for hypoplastic left heart syndrome without exposure to blood or blood products during his hospital stay. Perioperative techniques for blood avoidance are discussed with emphasis on their application to infants undergoing surgery for congenital heart disease. PMID:27729708

  19. Perioperative Management of a Child with Hypoplastic Left Heart Syndrome of the Jehovah's Witness Faith Presenting for Hybrid Comprehensive Stage II Procedure.

    PubMed

    Karuppiah, Sathappan; Mckee, Christopher; Hodge, Ashley; Galantowicz, Mark; Tobias, Joseph; Naguib, Aymen

    2016-09-01

    Over the years, there has been a growing recognition of the potential negative sequelae of allogeneic blood products on postoperative outcomes following cardiac surgery. In addition, followers of the Jehovah's Witness (JW) faith have a religious restriction against receiving blood or blood components. Advances in perioperative care, cardiopulmonary bypass (CPB), and surgical technique have minimized the need for allogeneic blood products. Specific blood conservation strategies include maximizing the preoperative hematocrit and coagulation function as well as intraoperative strategies, such as acute normovolemic hemodilution and adjustments of the technique of CPB. We report a 7-month-old patient whose parents were of the JW faith who underwent a comprehensive stage II procedure for hypoplastic left heart syndrome without exposure to blood or blood products during his hospital stay. Perioperative techniques for blood avoidance are discussed with emphasis on their application to infants undergoing surgery for congenital heart disease.

  20. Compound heterozygote (C282Y/H63D) of hereditary hemochromatosis in a 16-year-old girl with hypoplastic kidney.

    PubMed

    Kaczorowska-Hac, Barbara; Sikorska, Katarzyna; Bielawski, Krzysztof P; Schramm, Krystyna; Balcerska, Anna

    2007-05-01

    Iron-overload diseases are associated with primary or secondary disturbances of iron metabolism. Hereditary hemochromatosis, a genetically heterogeneous disease that is characterized by increased iron absorption and progressive deposition in parenchymal cells, may lead to organ damage and failure. Molecular studies have shown that hemochromatosis type 1 is predominantly due to a mutation in the HFE gene; there are 2 major mutations (C282Y and H63D). Disease symptoms are observed mostly after 40 years of age, often in men. We report the unusual case of a 16-year-old girl with an elevated serum iron level and a hypoplastic kidney. Identification of heterozygosity for the HFE gene mutation C282Y/H63D confirmed the diagnosis of hemochromatosis type 1. The early detection of hemochromatosis in the presented case may delay organ damage and failure due to iron overload.

  1. Study design and rationale for ELPIS: A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome.

    PubMed

    Kaushal, Sunjay; Wehman, Brody; Pietris, Nicholas; Naughton, Casey; Bentzen, Soren M; Bigham, Grace; Mishra, Rachana; Sharma, Sudhish; Vricella, Luca; Everett, Allen D; Deatrick, Kristopher B; Huang, Sihong; Mehta, Helina; Ravekes, William A; Hibino, Naru; Difede, Darcy L; Khan, Aisha; Hare, Joshua M

    2017-10-01

    Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow-derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell-based therapy for congenital heart disease patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Reversible ductus arteriosus constriction due to maternal indomethacin after fetal intervention for hypoplastic left heart syndrome with intact/restrictive atrial septum.

    PubMed

    Vogel, Melanie; Wilkins-Haug, Louise E; McElhinney, Doff B; Marshall, Audrey C; Benson, Carol B; Silva, Virginia; Tworetzky, Wayne

    2010-01-01

    Fetal cardiac intervention (FCI) has been performed at our center in selected fetuses with complex congenital heart disease since 2000. Most interventions are performed in fetuses with a ductus arteriosus (DA)-dependent circulation. Indomethacin promotes closure of the DA in newborns and in fetal life, a potentially life threatening complication in fetuses with ductus-dependent congenital heart disease. We reviewed our experience with FCI with a focus on the frequency, features, and clinical course of ductal constriction. Fetuses undergoing FCI receive comprehensive pre- and postoperative cardiac and cerebral ultrasound evaluation, approximately 24 hours before and after the procedure, including imaging of DA flow and Doppler assessment of the umbilical artery and vein, ductus venosus, and, since 2004, the middle cerebral artery. Among 113 fetuses that underwent FCI, 24 of which were older than 28 0/7 weeks gestation, 2 were found to have DA constriction due to indomethacin therapy within 24 hours of intervention. Both of these were 30-week fetuses with hypoplastic left heart syndrome and restrictive or intact atrial septum. The DA was stenotic by spectral and color Doppler, and middle cerebral and umbilical artery pulsatility indexes were depressed. After discontinuation of indomethacin, the Doppler indices improved or normalized. Close echocardiographic monitoring of fetal Doppler flow velocities is very important after fetal intervention and indomethacin treatment, as the consequences of DA constriction in a fetus with hypoplastic left heart syndrome are potentially lethal. Sonographic evaluation should include measurement of cerebral and umbilical arterial flow velocities as well as color and spectral Doppler interrogation of the DA. Copyright 2009 S. Karger AG, Basel.

  3. Lung cancer

    MedlinePlus

    ... Sputum test to look for cancer cells Thoracentesis (sampling of fluid buildup around the lung) In most ... quitting, talk with your provider. There are many methods to help you quit, from support groups to ...

  4. Lung Transplant

    MedlinePlus

    ... will recover in the hospital’s intensive care unit (ICU) before moving to a hospital room for one to three weeks. Your doctor may recommend pulmonary rehabilitation after your lung transplant surgery to help you ...

  5. Unexpandable lung.

    PubMed

    Pereyra, Marco F; Ferreiro, Lucía; Valdés, Luis

    2013-02-01

    Unexpandable lung is a mechanical complication by which the lung does not expand to the chest wall, impeding a normal apposition between the two pleural layers. The main mechanism involved is the restriction of the visceral pleura due to the formation of a fibrous layer along this pleural membrane. This happens because of the presence of an active pleural disease (lung entrapment), which can be resolved if proper therapeutic measures are taken, or a remote disease (trapped lung), in which an irreversible fibrous pleural layer has been formed. The clinical suspicion arises with the presence of post-thoracocentesis hydropneumothorax or a pleural effusion that cannot be drained due to the appearance of thoracic pain. The diagnosis is based on the analysis of the pleural liquid, the determination of pleural pressures as we drain the effusion and on air-contrast chest CT. As both represent the continuity of one same process, the results will depend on the time at which these procedures are done. If, when given a lung that is becoming entrapped, the necessary therapeutic measures are not taken, the final result will be a trapped lung. In this instance, most patients are asymptomatic or have mild exertional dyspnea and therefore they do not require treatment. Nevertheless, in cases of incapacitating dyspnea, it may be necessary to use pleural decortication in order to resolve the symptoms. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.

  6. Eyes absent 1 (Eya1) is a critical coordinator of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

    PubMed Central

    El-Hashash, Ahmed HK; Alam, Denise Al; Turcatel, Gianluca; Bellusci, Saverio; Warburton, David

    2011-01-01

    The proper level of proliferation and differentiation along the proximodistal axis is crucial for lung organogenesis. Elucidation of the factors that control these processes will therefore provide important insights into embryonic lung development and regeneration. Eya1 is a transcription factor/protein phosphatase that regulates cell lineage specification and proliferation. Yet its functions during lung development are unknown. In this paper we show that Eya1-/- lungs are severely hypoplastic with reduced epithelial branching and increased mesenchymal cellularity. Eya1 is expressed at the distal epithelial tips of branching tubules as well as in the surrounding distal mesenchyme. Eya1-/- lung epithelial cells show loss of progenitor cell markers with increased expression of differentiation markers and cell cycle exit. In addition, Eya1–/– embryos and newborn mice exhibit severe defects in the smooth muscle component of the bronchi and major pulmonary vessels with decreased Fgf10 expression. These defects lead to rupture of the major vessels and hemorrhage into the lungs after birth. Treatment of Eya1-/- epithelial explants in culture with recombinant Fgf10 stimulates epithelial branching. Since Shh expression and activity are abnormally increased in Eya1-/- lungs, we tested whether genetically lowering Shh activity could rescue the Eya1-/- lung phenotype. Indeed, genetic reduction of Shh partially rescues Eya1-/- lung defects while restoring Fgf10 expression. This study provides the first evidence that Eya1 regulates Shh signaling in embryonic lung, thus ensuring the proper level of proliferation and differentiation along the proximodistal axis of epithelial, mesenchymal and endothelial cells. These findings uncover novel functions for Eya1 as a critical upstream coordinator of Shh-Fgf10 signaling during embryonic lung development. We conclude, therefore, that Eya1 function is critical for proper coordination of lung epithelial, mesenchymal and vascular

  7. Dynamic tracheal occlusion improves lung morphometrics and function in the fetal lamb model of congenital diaphragmatic hernia

    PubMed Central

    Jelin, Eric B.; Etemadi, Mozziyar; Encinas, Jose; Schecter, Samuel C.; Chapin, Cheryl; Wu, Jianfeng; Guevara-Gallardo, Salvador; Nijagal, Amar; Gonzales, Kelly D.; Ferrier, William T.; Roy, Shuvo; Miniati, Doug

    2011-01-01

    Background Congenital diaphragmatic hernia (CDH) is associated with significant neonatal morbidity and mortality. Although prenatal complete tracheal occlusion (cTO) causes hypoplastic CDH lungs to enlarge, improved lung function has not been demonstrated. Furthermore, cTO interferes with the dynamic pressure change and fluid flow associated with fetal breathing. Purpose To assess a novel dynamic tracheal occlusion (dTO) device that preserves pressure changes and fluid flow. Methods In this pilot study, CDH was created in fetal lambs at 65 days gestational age (GA). At 110 days GA, a cTO device (n=3) or a dTO device (n=4) was placed in the fetal trachea. At 135 days GA, lambs were delivered and resuscitated. Unoperated lamb co-twins (n=5), sham thoracotomy lambs (n=2), and untreated CDH lambs (n=3) served as controls. Results Tracheal opening pressure, lung volume, lung fluid total protein, and phospholipid were significantly higher in the cTO group than in the dTO and unoperated control groups. Maximal oxygenation and lung compliance were significantly lower in the cTO group when compared to the unoperated control and dTO groups. Conclusion Preliminary results suggest that in the fetal lamb CDH model, dTO restores normal lung morphometrics and function, whereas cTO leads to enlarged but less functional lungs. PMID:21683214

  8. Amniotic fluid derived mesenchymal stromal cells augment fetal lung growth in a nitrofen explant model.

    PubMed

    Di Bernardo, Julie; Maiden, Michael M; Hershenson, Marc B; Kunisaki, Shaun M

    2014-06-01

    Recent experimental work suggests the therapeutic role of mesenchymal stromal cells (MSCs) during lung morphogenesis. The purpose of this study was to investigate the potential paracrine effects of amniotic fluid-derived MSCs (AF-MSCs) on fetal lung growth in a nitrofen explant model. Pregnant Sprague-Dawley dams were gavage fed nitrofen on gestational day 9.5 (E9.5). E14.5 lung explants were subsequently harvested and cultured ex vivo for three days on filter membranes in conditioned media from rat AF-MSCs isolated from control (AF-Ctr) or nitrofen-exposed (AF-Nitro) dams. The lungs were analyzed morphometrically and by quantitative gene expression. Although there were no significant differences in total lung surface area among hypoplastic lungs, there were significant increases in terminal budding among E14.5+3 nitrofen explants exposed to AF-Ctr compared to explants exposed to medium alone (58.8±8.4 vs. 39.0±10.0 terminal buds, respectively; p<0.05). In contrast, lungs cultured in AF-Nitro medium failed to augment terminal budding. Nitrofen explants exposed to AF-Ctr showed significant upregulation of surfactant protein C to levels observed in normal fetal lungs. AF-MSCs can augment branching morphogenesis and lung epithelial maturation in a fetal explant model of pulmonary hypoplasia. Cell therapy using donor-derived AF-MSCs may represent a novel strategy for the treatment of fetal congenital diaphragmatic hernia. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Rheumatoid lung disease

    MedlinePlus

    Lung disease - rheumatoid arthritis; Rheumatoid nodules; Rheumatoid lung ... Lung problems are common in rheumatoid arthritis. They often cause no symptoms. The cause of lung disease associated with rheumatoid arthritis is unknown. Sometimes, the medicines used to ...

  10. Nutrition for Lung Cancer

    MedlinePlus

    ... by zip code or Select your state State Lung Cancer www.lung.org > Lung Health and Diseases > ... I Stay Healthy Share this page: Nutrition for Lung Cancer Key Points There is no prescribed diet ...

  11. Lung Nodules: Overview

    MedlinePlus

    ... Research & Science Education & Training Home Conditions Lung Nodules Lung Nodules Make an Appointment Find a Doctor Ask ... Kern, MD (June 01, 2016) What is a lung nodule? A lung nodule is also called a ...

  12. Eosinophilic Lung Disorders

    MedlinePlus

    ... Education & Training Home Conditions Eosinophilic Lung Disorders Eosinophilic Lung Disorders Make an Appointment Find a Doctor Ask ... Rafeul Alam, MD, PhD (July 01, 2012) Eosinophilic lung disorders are a category of lung problems characterized ...

  13. Lung Nodules: Overview

    MedlinePlus

    ... Research & Science Education & Training Home Conditions Lung Nodules Lung Nodules Make an Appointment Find a Doctor Ask ... Kern, MD (June 01, 2016) What is a lung nodule? A lung nodule is also called a ...

  14. Lung Cancer Screening

    MedlinePlus

    Lung cancer screening Overview By Mayo Clinic Staff Lung cancer screening is a process that's used to detect the presence ... with a high risk of lung cancer. Lung cancer screening is recommended for older adults who are longtime ...

  15. Lung cancer - small cell

    MedlinePlus

    Cancer - lung - small cell; Small cell lung cancer; SCLC ... About 15% of all lung cancer cases are SCLC. Small cell lung cancer is slightly more common in men than women. Almost all cases of SCLC are ...

  16. Furrier's lung

    PubMed Central

    Pimentel, J. Cortez

    1970-01-01

    As is known, the inhalation of animal hairs can provoke immunological reactions in the respiratory tract affecting the naso-tracheo-bronchial sector and giving rise to asthma-like syndromes. Another form of disease, found in furriers with long exposure to `hair dust', is described. It is characterized by a granulomatous interstitial pneumonia, of the tuberculoid type, very similar to that described in other diseases related to the inhalation of organic dusts, both vegetable and animal, such as `farmer's lung' and `bird fancier's lung'. This new disease—which we experimentally reproduced—can be diagnosed from the occupational history together with the finding on lung biopsy of hair shafts within granulomatous lesions (birefringence and histo-chemical reactions). As in other diseases of this type, a host factor of probable immunological nature is suggested. Attention is drawn to the need to protect workers in the furrier's trade. Images PMID:5484998

  17. Tsunami lung.

    PubMed

    Inoue, Yoshihiro; Fujino, Yasuhisa; Onodera, Makoto; Kikuchi, Satoshi; Shozushima, Tatsuyori; Ogino, Nobuyoshi; Mori, Kiyoshi; Oikawa, Hirotaka; Koeda, Yorihiko; Ueda, Hironobu; Takahashi, Tomohiro; Terui, Katsutoshi; Nakadate, Toshihide; Aoki, Hidehiko; Endo, Shigeatsu

    2012-04-01

    We encountered three cases of lung disorders caused by drowning in the recent large tsunami that struck following the Great East Japan Earthquake. All three were females, and two of them were old elderly. All segments of both lungs were involved in all the three patients, necessitating ICU admission and endotracheal intubation and mechanical ventilation. All three died within 3 weeks. In at least two cases, misswallowing of oil was suspected from the features noted at the time of the detection. Sputum culture for bacteria yielded isolation of Stenotrophomonas maltophilia, Legionella pneumophila, Burkholderia cepacia, and Pseudomonas aeruginosa. The cause of tsunami lung may be a combination of chemical induced pneumonia and bacterial pneumonia.

  18. Lung imaging.

    PubMed

    Ley, Sebastian

    2015-06-01

    Imaging of the lung is a mainstay of respiratory medicine. It provides local information about morphology and function of the lung parenchyma that is unchallenged by other noninvasive techniques. During the 2014 European Respiratory Society International Congress in Munich, Germany, a Clinical Year in Review session was held focusing on the latest developments in pulmonary imaging. This review summarises some of the main findings of peer-reviewed articles that were published in the 12-month period prior to the 2014 International Congress. Copyright ©ERS 2015.

  19. [Humidifier lung].

    PubMed

    Gerber, P; de Haller, R; Pyrozynski, W J; Sturzenegger, E R; Brändli, O

    1981-02-07

    Breathing air from a humidifier or an air conditioning unit contaminated by various microorganisms can cause an acute lung disease involving fever, cough and dyspnea, termed "humidifier fever". This type of hypersensitivity pneumonitis was first described in 1959 by PESTALOZZI in the Swiss literature and subsequently by BANASZAK et al. in the Anglo-American. Here a chronic form of this disease which led to pulmonary fibrosis is described: A 37-year-old woman who works in a cheese shop presented with dyspnea which had been progressive over two years, weight loss, a diffuse reticular pattern radiographically and a severe restrictive defect in lung function tests. Open lung biopsy revealed chronic interstitial and alveolar inflammation with non-caseating granulomas and fibrotic changes. Circulating immune complexes and precipitins against the contaminated humidifier water and cheese mites were found, but no antibodies suggesting legionnaires' disease. Two out of five otherwise healthy employees of this cheese shop, where a new humidifying system had been installed 7 years earlier, also had precipitins against the contaminated water from the humidifier and the cheese mites. Despite ending of exposure and longterm steroid and immunosuppressive therapy, the signs and symptoms of pulmonary fibrosis persisted. Contrary to the acute disease, this chronic form is termed "humidifier lung". The importance is stressed of investigating the possibility of exposure to contaminated humidifiers or air conditioning units in all cases of newly detected pulmonary fibrosis.

  20. Normal Range of Fetal Nasal Bone Length during the Second Trimester in an Afro-Caribbean Population and Likelihood Ratio for Trisomy 21 of Absent or Hypoplastic Nasal Bone.

    PubMed

    Gautier, Manuella; Gueneret, Michèle; Plavonil, Corinne; Jolivet, Eugénie; Schaub, Bruno

    2017-01-01

    To establish the normal reference range of fetal nasal bone length (NBL) during the second trimester in an Afro-Caribbean population and the likelihood ratio (LR) for fetal trisomy 21. Prenatal records of euploid, non-malformed singleton fetuses who underwent second-trimester ultrasonographic scans at 20-24 weeks of gestation were retrospectively analyzed for NBL and gestational age (GA). Only Afro-Caribbean couples were selected. The relationship between fetal NBL and GA was determined. The data of all fetuses with Down syndrome were provided by the French West Indies Register of Congenital Malformations (REMALAN). There was a significant linear association between fetal NBL and GA (R2 = 0. 354). The 50th percentile for NBL increased from 5.0 to 7.0 mm from week 20 to 24 of gestation. The nasal bone (NB) was absent or hypoplastic in 8.6% of the euploid fetuses and in 69.2% of the trisomy 21 fetuses. The LR for trisomy 21 of absent or hypoplastic NB in an Afro-Caribbean population was 8.02, but only 2.32 when this sign was isolated. The reference range for fetal NBL at 20-24 weeks of gestation in an Afro-Caribbean population and the LR for trisomy 21 of absent or hypoplastic NB differed from the other populations. © 2016 S. Karger AG, Basel.

  1. What Are Lung Carcinoid Tumors?

    MedlinePlus

    ... Carcinoid Tumor About Lung Carcinoid Tumors What Are Lung Carcinoid Tumors? Lung carcinoid tumors (also known as ... lungs, as well as the neuroendocrine system. The lungs The lungs are 2 sponge-like organs in ...

  2. Somatic mutations in NKX2–5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart.

    PubMed

    Esposito, Giorgia; Butler, Tanya L; Blue, Gillian M; Cole, Andrew D; Sholler, Gary F; Kirk, Edwin P; Grossfeld, Paul; Perryman, Benjamin M; Harvey, Richard P; Winlaw, David S

    2011-10-01

    The majority of congenital heart disease (CHD) occurs as a sporadic finding, with a minority of cases associated with a known genetic abnormality. Combinations of genetic and environmental factors are implicated, with the recent and intriguing hypothesis that an apparently high rate of somatic mutations might explain some sporadic CHD. We used samples of right ventricular myocardium from patients undergoing surgical repair of tetralogy of Fallot (TOF) and hypoplastic left heart (HLH) to examine the incidence of somatic mutation in cardiac tissue. TOF is a common form of cyanotic CHD, occurring in 3.3 per 10,000 live births. HLH is a rare defect in which the left side of the heart is severely under-developed. Both are severe malformations whose genetic etiology is largely unknown. We carried out direct sequence analysis of the NKX2–5 and GATA4 genes from fresh frozen cardiac tissues and matched blood samples of nine TOF patients. Analysis of NKX2–5, GATA4, and HAND1 was performed from cardiac tissue of 24 HLH patients and three matched blood samples. No somatic or germline mutations were identified in the TOF or HLH patients. Although limited by sample size, our study suggests that somatic mutations in NKX2–5 and GATA4 are not a common cause of isolated TOF or HLH.

  3. Mid-Term Outcomes of a Modification of Extended Aortic Arch Anastomosis with Pulmonary Artery Banding in Single Ventricle Neonates with Hypoplastic Transverse Arch

    PubMed Central

    Thang, Bui Quoc; Furugaki, Tatsuya; Osaka, Motoo; Watanabe, Yutaka; Kanemoto, Shinya; Suetsugu, Fuminaga

    2016-01-01

    Purpose: There is less certainty regarding the best strategy for treating neonates with functional single ventricle (SV) and hypoplastic aortic arch. We have applied a modified extended aortic arch anastomosis (EAAA) and main pulmonary artery banding (PAB) as an initial palliation in neonates with transverse arch hypoplasia and assessed the mid-term outcomes. Methods: In total, 10 neonates with functional SV and extensive hypoplasia or interruption of the arch underwent a modified EAAA (extended arch anastomosis with a subclavian flap) concomitant with main PAB through a thoracotomy without cardiopulmonary bypass. Patient age and weight ranged from 4 to 14 days and 2.3 to 3.8 kg, respectively. Results: There were no hospital deaths although there were two late deaths. Gradients across the arch were 0 to 7 mmHg at postoperative day 1 and no arch reoperations were required. Two patients required balloon aortoplasty. Nine underwent bidirectional cavopulmonary shunt and two of them needed concomitant Damus–Kaye–Stansel (DKS) anastomosis. Six have completed Fontan. Conclusion: Our modification of EAAA with main PAB for SV neonates may benefit a certain population with transverse arch hypoplasia as an option to be considered. Patients with the potential for developing outflow obstruction may be best managed with an initial DKS-type palliation. PMID:27725352

  4. Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

    PubMed

    Poulter, James A; El-Sayed, Walid; Shore, Roger C; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-01-01

    The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.

  5. Computational modelling of the hybrid procedure in hypoplastic left heart syndrome: a comparison of zero-dimensional and three-dimensional approach.

    PubMed

    Young, Andrew; Gourlay, Terry; McKee, Sean; Danton, Mark H D

    2014-11-01

    Previous studies have employed generic 3D-multiscale models to predict haemodynamic effects of the hybrid procedure in hypoplastic left heart syndrome. Patient-specific models, derived from image data, may allow a more clinically relevant model. However, such models require long computation times and employ internal pulmonary artery band [dint] dimension, which limits clinical application. Simpler, zero-dimensional models utilize external PAB diameters [dext] and provide rapid analysis, which may better guide intervention. This study compared 0-D and 3-D modelling from a single patient dataset and investigated the relationship dint versus dext and hemodynamic outputs of the two models. Optimum oxygen delivery defined at dint=2mm corresponded to dext=3.1 mm and 3.4 mm when models were matched for cardiac output or systemic pressure, respectively. 0-D and 3-D models when matched for PAB dimension produced close equivalence of hemodynamics and ventricular energetics. From this study we conclude that 0-D model can provide a valid alternative to 3D-multiscale in the hybrid-HLHS circulation. Copyright © 2014. Published by Elsevier Ltd.

  6. Parents' perceptions during the transition to home for their child with a congenital heart defect: How can we support families of children with hypoplastic left heart syndrome?

    PubMed

    March, Sarita

    2017-07-01

    The aim of the study was to explore the literature related to transitions in healthcare between the hospital and home that caregivers experience with a child who has a congenital heart defect (CHD), specifically related to hypoplastic left heart syndrome (HLHS). A systematic literature review was conducted searching OVID Medline, CINAHL, and PubMed to discover the caregivers' perceptions on their transitions between hospital care and home care of their child with a CHD. Articles included those with focus on the transitions of caregivers between hospital and home care for children with CHD. Excluded articles were studies focused on adolescents, transition to adult healthcare, mortality results, other diseases associated with CHDs, comparison of CHD treatments, feasibility studies, differences in care between hospitals, home monitoring, and comparison of videoconference and telephone home communication. Ten articles were selected. Many parents voiced their concerns with feeding their child, learning medical skills and knowledge, reported a disrupted relationship between parents and their child, and identified stress and anxiety associated with taking care of a child with a CHD. There were limited studies on caregivers' transitions with a child with HLHS, but there also was limited focus on the caregivers' experiences with transitions between hospital and home care for their child with any CHD. Research on the transition experience between hospital care and home care for caregivers of children born with a CHD, and a specific focus on HLHS from the caregivers' viewpoint, would provide insight into the perspective of caregivers during the numerous transitions. © 2017 Wiley Periodicals, Inc.

  7. Reflux and Lung Disease

    MedlinePlus

    ... Healthy Eating Reflux and Lung Disease Reflux and Lung Disease Make an Appointment Ask a Question Find a Doctor Many people with chronic lung disease also suffer from gastroesophageal reflux (GERD). In this ...

  8. Interstitial Lung Disease

    MedlinePlus

    ... Conditions Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Interstitial Lung Disease (ILD)/Pulmonary Fibrosis Make an Appointment Refer ... ILD clinical trials and most effective therapies. Interstitial Lung Disease Care at National Jewish Health At National ...

  9. Amniotic lamellar body count and congenital diaphragmatic hernia in humans and in a rat model.

    PubMed

    Watanabe, Yuriko; Tsuda, Hiroyuki; Kotani, Tomomi; Sumigama, Seiji; Mano, Yukio; Hayakawa, Masahiro; Sato, Yoshiaki; Kikkawa, Fumitaka

    2013-03-01

    We examined the extent of fetal lung hypoplasia and lung maturation using the amniotic lamellar body count (LBC) in congenital diaphragmatic hernia (CDH). We obtained 30 amniotic fluid samples from human CDH cases during cesarean section. We assessed LBC, magnetic resonance imaging (MRI), and ultrasound findings for predicting the prognosis of CDH. We collected newborn amniotic fluid and lung tissue at embryonic day (E)21 from normal and nitrofen-induced CDH rats (administered 100 mg orally at E9). Amniotic LBCs in rats were measured using light microscopy. In human CDH, LBC was significantly higher in the surviving than in the deceased group (P < 0.01). A significant positive correlation was observed between LBC and percentage of fetal lung volume on MRI (P < 0.001; r = 0.716). In rats, LBC was significantly higher in controls than in CDH rats (P < 0.01) and correlated with fetal lung weight. We conclude that LBC is useful for predicting lung hypoplasia in human CDH after 35 gestational weeks and in a rat model of nitrofen-induced CDH.

  10. Restrictive Atrial Septum Defect Becomes a Risk Factor for Norwood Palliation of Hypoplastic Left Heart Syndrome Only When It Is Combined with Mitral or Aortic Atresia.

    PubMed

    Sata, Sojiro; Sinzobahamvya, Nicodème; Arenz, Claudia; Zartner, Peter; Asfour, Boulos; Hraska, Viktor

    2015-08-01

    Restrictive atrial septal defect (ASD) is described as risk factor for Norwood procedure because of elevated pulmonary resistance. We hypothesized that it invariably could not cause pulmonary hypertension, unless it was combined with mitral valve or aortic valve atresia. We investigated how restrictive ASD influenced survival of patients with hypoplastic left heart syndrome (HLHS) who underwent Norwood operation. A total of 118 HLHS patients who underwent surgery between January 2005 and December 2012 were grouped into three groups. Group 1 included 31 patients with restrictive ASD combined with mitral or aortic atresia; Group 2 composed of 12 patients with restrictive ASD and mitral and aortic stenosis; Group 3 (n = 75) had no ASD restriction. Survival was determined for each group. Multivariate analysis was conducted to test risk factors for mortality. Mean follow-up was 26.3 ± 24.1 months. Survival was 78.7% ± 4.2% at 30-month interval and onward after Norwood procedure for the whole cohort; it was 43.8% ± 10.0%, 91.7% ± 8.0%, and 77.3% ± 5.0% for Group 1, 2, and 3, respectively. The difference was significant between Group 1 and Group 2 and 3: p < 0.001. Survival was similar for Group 2 and Group 3: p = 0.45. Combination of restrictive ASD and mitral or aortic atresia was found to be the sole risk factor for early and late mortality (odds ratio: 3.5, 95% confidence interval: 1.8-7.1, p < 0.001). Restrictive ASD only affects survival of HLHS patients following Norwood procedure if it is associated with mitral or aortic atresia. Georg Thieme Verlag KG Stuttgart · New York.

  11. Effect of endovascular stenting of right ventricle to pulmonary artery conduit stenosis in infants with hypoplastic left heart syndrome on stage II outcomes.

    PubMed

    Gray, Robert G; Minich, L Luann; Weng, Hsin Yi; Heywood, Mason C; Burch, Phillip T; Cowley, Collin G

    2012-07-01

    There is growing awareness that the Norwood procedure with the Sano modification is prone to early right ventricular to pulmonary artery (RV-PA) conduit stenosis resulting in systemic oxygen desaturation, increased interstage morbidity, and death. We report our experience with endovascular stent placement for conduit stenosis and compare the outcomes at stage II surgery between stented and nonstented infants. The medical records of all patients with hypoplastic left heart syndrome who received an RV-PA conduit at Norwood palliation from May 2005 to January 2010 were reviewed. The preoperative anatomy, demographics, operative variables, and outcomes pertaining to the Norwood and subsequent stage II surgeries were obtained and compared between stented and nonstented infants. The pre- and post-stent oxygen saturation, stenosis location, type and number of stents implanted, concomitant interventions, procedure-related complications, and reinterventions were collected. Of the 66 infants who underwent the Norwood procedure with RV-PA conduit modification, 16 (24%) received stents. The anatomy, demographics, and outcome variables after the Norwood procedure were similar between the stented and nonstented infants. The age at catheterization was 93 ± 48 days, and the weight was 4.9 ± 1.2 kg. The oxygen saturation increased from 66 ± 9% before intervention to 82 ± 6% immediately after stenting (p <0.0001). No interstage surgical shunt revisions were performed in either group. Age, weight, pre-stage II echocardiographic variables, oxygen saturation, and operative and outcome variables, including mortality, were similar between the 2 groups. In conclusion, endovascular stent placement for RV-PA conduit stenosis after the Norwood procedure leads to improved systemic oxygen levels and prevents early performance of stage II surgery without compromising stage II outcomes.

  12. Chromosome anomalies in bone marrow as primary cause of aplastic or hypoplastic conditions and peripheral cytopenia: disorders due to secondary impairment of RUNX1 and MPL genes

    PubMed Central

    2012-01-01

    Background Chromosome changes in the bone marrow (BM) of patients with persistent cytopenia are often considered diagnostic for a myelodysplastic syndrome (MDS). Comprehensive cytogenetic evaluations may give evidence of the real pathogenetic role of these changes in cases with cytopenia without morphological signs of MDS. Results Chromosome anomalies were found in the BM of three patients, without any morphological evidence of MDS: 1) an acquired complex rearrangement of chromosome 21 in a boy with severe aplastic anaemia (SAA); the rearrangement caused the loss of exons 2–8 of the RUNX1 gene with subsequent hypoexpression. 2) a constitutional complex rearrangement of chromosome 21 in a girl with congenital thrombocytopenia; the rearrangement led to RUNX1 disruption and hypoexpression. 3) an acquired paracentric inversion of chromosome 1, in which two regions at the breakpoints were shown to be lost, in a boy with aplastic anaemia; the MPL gene, localized in chromosome 1 short arms was not mutated neither disrupted, but its expression was severely reduced: we postulate that the aplastic anaemia was due to position effects acting both in cis and in trans, and causing Congenital Amegakaryocytic Thrombocytopenia (CAMT). Conclusions A clonal anomaly in BM does not imply per se a diagnosis of MDS: a subgroup of BM hypoplastic disorders is directly due to chromosome structural anomalies with effects on specific genes, as was the case of RUNX1 and MPL in the patients here reported with diagnosis of SAA, thrombocytopenia, and CAMT. The anomaly may be either acquired or constitutional, and it may act by deletion/disruption of the gene, or by position effects. Full cytogenetic investigations, including a-CGH, should always be part of the diagnostic evaluation of patients with BM aplasia/hypoplasia and peripheral cytopenias. PMID:23025896

  13. Outcomes of management decisions by parents for their infants with hypoplastic left heart syndrome born with and without a prenatal diagnosis.

    PubMed

    Tibballs, James; Cantwell-Bartl, Annie

    2008-06-01

    To study the influence of a prenatal diagnosis on parental choice of treatment for infants born with hypoplastic left heart syndrome (HLHS). Retrospective review of medical records of infants admitted to a paediatric tertiary hospital 1983-2004 with a diagnosis of HLHS. A total of 201 infants had HLHS diagnosed by echocardiography after birth with 129 subsequently undergoing surgery and 72 non-surgical management (compassionate/comfort care). When the diagnosis of HLHS was made prenatally, 68 of 71 (96%) infants underwent surgery whereas when the diagnosis was made post-natally 61 of 130 (47%) infants underwent surgery. Prenatal diagnosis was significantly associated with a parental choice of surgery (P < 0.001). Among 72 infants managed non-surgically, compassionate care was chosen by parents for 49 (68%) despite being fit for surgery, 20 (28%) were deemed unfit for surgery and in three (4%) the reasons for non-surgical management were unknown. Of the total 178 infants considered fit for surgery, 68 (38%) had had a prenatal diagnosis and 110 (62%) did not. Of 20 considered unfit for surgery, none had had a prenatal diagnosis. A prenatal diagnosis was significantly associated with fitness for surgery (P < 0.001). Approximately half of parents chose non-surgical management (compassionate care) of their infant if the diagnosis was post-natal. Although most parents of infants born with a prenatal diagnosis of HLHS chose surgical management of their infant, this is the likely influence of termination of pregnancy for this condition. Lack of prenatal diagnosis compromised fitness for surgery.

  14. Oxygen supply to the fetal cerebral circulation in hypoplastic left heart syndrome: a simulation study based on the theoretical models of fetal circulation.

    PubMed

    Sakazaki, Sayaka; Masutani, Satoshi; Sugimoto, Masaya; Tamura, Masanori; Kuwata, Seiko; Kurishima, Clara; Saiki, Hirofumi; Iwamoto, Yoichi; Ishido, Hirotaka; Senzaki, Hideaki

    2015-03-01

    Hypoxia due to congenital heart diseases (CHDs) adversely affects brain development during the fetal period. Head circumference at birth is closely associated with neuropsychiatric development, and it is considerably smaller in newborns with hypoplastic left heart syndrome (HLHS) than in normal newborns. We performed simulation studies on newborns with CHD to evaluate the cerebral circulation during the fetal period. The oxygen saturation of cerebral blood flow in newborns with CHD was simulated according to a model for normal fetal circulation in late pregnancy. We compared the oxygen saturation of cerebral blood flow between newborns with tricuspid atresia (TA; a disease showing univentricular circulation and hypoplasia of the right ventricle), those with transposition of the great arteries (TGA; a disease showing abnormal mixing of arterial and venous blood), and those with HLHS. The oxygen saturation of cerebral blood flow in newborns with normal circulation was 75.7 %, whereas it was low (49.5 %) in both newborns with HLHS and those with TA. Although the oxygen level is affected by the blood flow through the foramen ovale, the oxygen saturation in newborns with TGA was even lower (43.2 %). These data, together with previous reports, suggest that the cerebral blood flow rate is decreased in newborns with HLHS, and the main cause was strongly suspected to be retrograde cerebral perfusion through a patent ductus arteriosus. This study provides important information about the neurodevelopmental prognosis of newborns with HLHS and suggests the need to identify strategies to resolve this unfavorable cerebral circulatory state in utero.

  15. Epidemiology of Noncomplex Left Ventricular Outflow Tract Obstruction Malformations (Aortic Valve Stenosis, Coarctation of the Aorta, Hypoplastic Left Heart Syndrome) in Texas, 1999 –2001

    PubMed Central

    McBride, Kim L.; Marengo, Lisa; Canfield, Mark; Langlois, Peter; Fixler, David; Belmont, John W.

    2006-01-01

    BACKGROUND The left ventricular outflow tract (LVOT) malformations aortic valve stenosis (AVS), coarctation of the aorta (CoA), and hypoplastic left heart syndrome (HLHS) contribute significantly to infant mortality due to birth defects. Previous epidemiology data showed rate differences between male and female and white and black ethnic groups. The Texas Birth Defects Registry, an active surveillance program, enables study in a large, diverse population including Hispanics. METHODS Records of children up to 1 year old with AVS, CoA, and HLHS born in Texas from 1999 to 2001, were collected from the registry. Those including additional heart defects or a chromosomal anomaly were excluded. Multivariate analysis included: infant sex; United States–Mexico border county residence; and maternal age, race/ethnicity, birthplace, and education. RESULTS There were 910 cases among 1.08 million live births, of which 499 met inclusion criteria. Multivariate modeling of all LVOT malformations combined demonstrated lower prevalence rate ratios (PRRs) for black males (0.26) and Hispanic males (0.70). Similar results were found for CoA but not AVS or HLHS. Higher PRRs were noted for increased maternal age for LVOT (1.3 for 24–34 years; 1.7 for >34 years), AVS, and HLHS, but not CoA, and higher PRRs across all diagnoses for males (LVOT PRR, 2.4) were noted. CoA PRRs were higher in border county vs. non–border county residents (PRR, 2.1). Maternal education and birthplace were not significant factors. CONCLUSIONS There are rate differences for males among all 3 ethnic groups. Sex and ethnic differences suggest genetic etiologies, where the ethnic differences could be used to find susceptibility loci with mapping by admixture linkage disequilibrium. Increased CoA rates along the U.S.–Mexico border suggest environmental causes that will require further monitoring. PMID:16007587

  16. Analysis of preoperative condition and interstage mortality in Norwood and hybrid procedures for hypoplastic left heart syndrome using the Aristotle scoring system.

    PubMed

    Lloyd, David F A; Cutler, Lindsay; Tibby, Shane M; Vimalesvaran, Sunitha; Qureshi, Shakeel Ahmed; Rosenthal, Eric; Anderson, David; Austin, Conal; Bellsham-Revell, Hannah; Krasemann, Thomas

    2014-05-01

    The 'hybrid procedure', consisting of surgical banding of the pulmonary arteries with intraoperative stenting of the arterial duct, was developed as primary palliation in hypoplastic left heart syndrome (HLHS), avoiding the risks of cardiopulmonary bypass. In many centres, it is reserved for low birth weight, premature or unstable neonates; however, its role in such high risk cases of HLHS has yet to be defined. The preoperative condition of all patients with HLHS who underwent either the hybrid or the Norwood procedure for HLHS between 2005-2011 was analysed retrospectively, using a modified comprehensive Aristotle score. We then compared operative, interstage and 1 year mortalities between the groups after Aristotle adjustment via Cox proportional hazards analyses. Of 138 patients with HLHS, 27 had hybrid and 111 Norwood procedures. The hybrid group had significantly higher Aristotle scores (mean 4.1 vs 1.8; p<0.001); however, there was no significant difference in mortality at any stage. At 1 year, the overall unadjusted survival among Norwood and hybrid patients was 58.6% and 51.9%, respectively, yielding an Aristotle adjusted hazard ratio for mortality among hybrid patients of 1.09 (95% CI 0.56 to 2.11, p=0.80). Applying a hybrid approach to high risk patients with HLHS produces a comparable early and interstage mortality risk to lower risk patients undergoing the Norwood procedure. Prospective studies are needed to establish whether the hybrid procedure is a viable alternative to the Norwood procedure in all HLHS patients in terms of both mortality and long term morbidity.

  17. Pressure-volume loop-derived cardiac indices during dobutamine stress: a step towards understanding limitations in cardiac output in children with hypoplastic left heart syndrome.

    PubMed

    Wong, James; Pushparajah, Kuberan; de Vecchi, Adelaide; Ruijsink, Bram; Greil, Gerald F; Hussain, Tarique; Razavi, Reza

    2017-03-01

    Children with a single systemic right ventricle, such as in hypoplastic left heart syndrome (HLHS), frequently experience reduced exercise capacity. Elucidating the causes could help with optimising treatment strategies. Prospective data from 10 consecutive symptomatic patients with HLHS undergoing clinical cardiac magnetic resonance with catheterisation (XMR) were analysed. Mean age 8.6years (range 3.5-11.6years), mean time since Fontan completion 5.5years. MR-compatible catheters were placed in the systemic right ventricle and branch pulmonary arteries to record pressures at rest, with dobutamine infusion at 10mcg/kg/min and at 20mcg/kg/min. Cine short-axis stacks of the ventricle were performed at each condition and used to construct pressure-volume loops. Compared to rest, cardiac index increased with low-dose dobutamine (p<0.01) with no further rise at peak stress despite a further, albeit, blunted rise in heart rate (p=0.002). A fall in stroke volume occurred (p=0.014) despite good contractility (74% increase, p=0.045) and a well-coupled ventriculo-arterial ratio. End-diastolic pressure and early active relaxation, markers of diastolic function, were normal at rest. However, preload fell at peak stress (p<0.008) while pulmonary vascular resistance (PVR) was low throughout. This group of HLHS patients demonstrated a fall in SV at peak stress, coinciding with a fall in preload. Markers of systolic and diastolic function remained normal. Failure to adequately fill the ventricle implies a ceiling of maximal flow through the Fontan circuit despite low PVR. Copyright © 2016. Published by Elsevier B.V.

  18. Head and neck vessel size by angiography predicts neo-aortic arch obstruction after Norwood/Sano operation for hypoplastic left heart syndrome.

    PubMed

    Seckeler, Michael D; Raucci, Frank J; Saunders, Christine; Gangemi, James J; Peeler, Benjamin B; Jayakumar, K Anitha

    2013-02-01

    To identify and predict neo-aortic arch obstruction (NAAO) in children after Norwood/Sano operation (NO) for hypoplastic left heart syndrome (HLHS). NAAO is associated with morbidity and mortality after NO for HLHS and no objective measure has predicted the initial occurrence of NAAO. Computational flow models of aortic coarctation demonstrate increased wall shear stress (WSS) in vessels proximal to the coarctation segment, which we believe also occurs with NAAO. These vessels respond by increasing their luminal diameter to maintain normal WSS. We hypothesized that the relative increase in diameters of head and neck vessels to the isthmus, as measured by angiography, would identify hemodynamically significant NAAO and predict future NAAO. Retrospective review of patients with HLHS and at least one catheterization with aortic angiography after NO. Diameters of head and neck vessels were totaled and divided by the isthmus diameter to give a head and neck index (HNI), which was compared to coarctation index (CI) for identifying and predicting future NAAO. Forty-four patients were identified, 17 with and 27 without NAAO. Receiver operator characteristic analysis using a value for CI ≤0.5 showed a sensitivity of 47% and specificity of 89%. For HNI, a value >2.65 gave a sensitivity of 77% and specificity of 93%. Three patients who developed NAAO after their initial catheterization had CI >0.5, but abnormally high HNI >2.65. HNI is a more robust indicator of hemodynamically significant NAAO than CI and may predict its future occurrence after NO for HLHS.

  19. Time-to-Surgery and Pre-operative Cerebral Hemodynamics Predict Post-operative White Matter Injury in Neonates with Hypoplastic Left Heart Syndrome

    PubMed Central

    Lynch, Jennifer M.; Buckley, Erin M.; Schwab, Peter J.; McCarthy, Ann L.; Winters, Madeline E.; Busch, David R.; Xiao, Rui; Goff, Donna A.; Nicolson, Susan C.; Montenegro, Lisa M.; Fuller, Stephanie; Gaynor, J. William; Spray, Thomas L.; Yodh, Arjun G.; Naim, Maryam Y.; Licht, Daniel J.

    2014-01-01

    Objective Hypoxic-ischemic white mater brain injury commonly occurs in neonates with hypoplastic left heart syndrome (HLHS). Approximately half of the HLHS survivors exhibit neurobehavioral symptoms believed to be associated with this injury, though the exact timing of the injury is not known. Methods Neonates with HLHS were recruited for pre- and post-operative monitoring of cerebral oxygen saturation (ScO2), cerebral oxygen extraction fraction (OEF), and cerebral blood flow (CBF) using two non-invasive optical-based techniques, namely diffuse optical spectroscopy and diffuse correlation spectroscopy. Anatomical magnetic resonance imaging (MRI) scans were performed prior to and approximately one week after surgery in order to quantify the extent and timing of the acquired white matter injury. Risk factors for developing new or worsened white matter injury were assessed using uni- and multi-variate logistic regression. Results Thirty-seven neonates with HLHS were studied. In a univariate analysis, neonates who developed a large volume of new, or worsened, postoperative white matter injury had a significantly longer time-to-surgery (p=0.0003). In a multivariate model, longer time between birth and surgery (i.e., time-to-surgery), delayed sternal closure, and higher pre-operative CBF were predictors of post-operative white matter injury. Additionally, longer time-to-surgery and higher pre-operative CBF on morning of surgery were correlated with lower ScO2 (p=0.03 and p=0.05) and higher OEF (p=0.05 and p=0.05). Conclusions Longer time-to-surgery is associated with new post-operative white matter injury in otherwise healthy neonates with HLHS. The results suggest that earlier Norwood palliation may decrease the likelihood of acquiring postoperative white matter injury. PMID:25109755

  20. Twin pregnancy complicated by esophageal atresia, duodenal atresia, gastric perforation, and hypoplastic left heart structures in one twin: a case report and review of the literature.

    PubMed

    Abou Chaar, Mohamad K; Meyers, Mariana L; Tucker, Bethany D; Galan, Henry L; Liechty, Kenneth W; Crombleholme, Timothy M; Marwan, Ahmed I

    2017-03-18

    The antenatal diagnosis of a combined esophageal atresia without tracheoesophageal fistula and duodenal atresia with or without gastric perforation is a rare occurrence. These diagnoses are difficult and can be suspected on ultrasound by nonspecific findings including a small stomach and polyhydramnios. Fetal magnetic resonance imaging adds significant anatomical detail and can aid in the diagnosis of these complicated cases. Upon an extensive literature review, there are no reports documenting these combined findings in a twin pregnancy. Therefore we believe this is the first case report of an antenatal diagnosis of combined pure esophageal and duodenal atresia in a twin gestation. We present a case of a 30-year-old G1P0 white woman at 22-week gestation with a monochorionic-diamniotic twin pregnancy discordant for esophageal atresia, duodenal atresia with gastric perforation, hypoplastic left heart structures, and significant early gestation maternal polyhydramnios. In this case, fetal magnetic resonance imaging was able to depict additional findings including area of gastric wall rupture, hiatal hernia, dilation of the distal esophagus, and area of duodenal obstruction and thus facilitated the proper diagnosis. After extensive counseling at our multidisciplinary team meeting, the parents elected to proceed with radiofrequency ablation of the anomalous twin to maximize the survival of the normal co-twin. The procedure was performed successfully with complete cessation of flow in the umbilical artery and complete cardiac standstill in the anomalous twin with no detrimental effects on the healthy co-twin. Prenatal diagnosis of complex anomalies in twin pregnancies constitutes a multitude of ethical, religious, and cultural factors that come into play in the management of these cases. Fetal magnetic resonance imaging provides detailed valuable information that can assist in management options including possible prenatal intervention. The combination of a cystic

  1. Fifteen-year single center experience with the "Giessen Hybrid" approach for hypoplastic left heart and variants: current strategies and outcomes.

    PubMed

    Schranz, Dietmar; Bauer, Anna; Reich, Bettina; Steinbrenner, Blanka; Recla, Sabine; Schmidt, Dorle; Apitz, Christian; Thul, Josef; Valeske, Klaus; Bauer, Jürgen; Müller, Matthias; Jux, Christian; Michel-Behnke, Ina; Akintürk, Hakan

    2015-02-01

    Presented is a retrospective outcome study of a 15-year single institutional experience with a contemporary cohort of patients with hypoplastic left heart syndrome and complex that underwent a "Giessen Hybrid" stage I as initial palliation. Hybrid approach consisting of surgical bilateral pulmonary artery banding and percutaneous duct stenting with or without atrial septum manipulation was developed from a rescue approach to a first-line procedure. Comprehensive Aristotle score defined pre-operative condition. Fifteen-year follow-up mortality is reported as occurring within the staged univentricular palliation or before and after biventricular repair. Hybrid stage I was performed in 154 patients; 107 should be treated by single ventricle palliation, 33 by biventricular repair (BVR), 7 received heart transplantation, and 7 were treated by comfort care, respectively. Overall 34 children died. The Aristotle score (mean value 18.2 ± 3) classified for univentricular circulations in newborns did not have statistical impact on the outcome. Two patients died during stage I (1.2%), and the interstage I mortality was 6.7%, and stage II mortality 9%, respectively. Stage III was up to now performed in 57 patients without mortality. At 1 year, the overall unadjusted survival of HLHS and variants was 84% and following BVR 89%, respectively. The Fifteen-year survival rate for HLHS and variants was 77%, with no significant impact of birth weight of less than 2.5 kg. In conclusion, Hybrid stage I fulfilled the criteria of life-saving approach. In our institution, Hybrid procedure replaced Norwood-staged palliation with a considerable mid- and long-term survival rate. Considering interstage mortality close surveillance is mandatory.

  2. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  3. Risks of Lung Cancer Screening

    MedlinePlus

    ... Treatment Lung Cancer Prevention Lung Cancer Screening Research Lung Cancer Screening (PDQ®)–Patient Version What is screening? ... These are called diagnostic tests . General Information About Lung Cancer Key Points Lung cancer is a disease ...

  4. Lung surfactant.

    PubMed Central

    Rooney, S A

    1984-01-01

    Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, beta-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed. PMID:6145585

  5. Interstitial Lung Diseases

    MedlinePlus

    Interstitial lung disease is the name for a large group of diseases that inflame or scar the lungs. The inflammation and scarring make it hard to ... air is responsible for some types of interstitial lung diseases. Specific types include Black lung disease among ...

  6. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  7. Unilateral right pulmonary artery agenesis and congenital cystic adenomatoid malformation of the right lung with Ortner's syndrome.

    PubMed

    David, Jane Jackie; Mohanlal, Smilu; Sankhe, Punam; Ghildiyal, Radha

    2016-01-01

    We report a 2.5-year-old girl who presented with hoarseness of voice since 3 months of age and failure to thrive. Chest X-ray showed cardiomegaly with a deviation of the trachea and mediastinum to the right side. Two-dimensional echocardiography showed decreased flow across the right pulmonary artery, a small atrial septal defect (ASD) with a right-to-left shunt, and a dilated right atrium and right ventricle with severe tricuspid regurgitation suggestive of severe pulmonary hypertension. A silent large patent ductus arteriosus was also seen. Multiple detector computerized tomography aortogram confirmed the findings of absent right pulmonary artery and hypoplastic right lung with small cystic lesions suggestive of congenital cystic adenomatoid malformation in the right lower lobe. Hoarseness of voice was due to the left vocal cord palsy probably secondary to severe pulmonary hypertension (Ortner's syndrome).

  8. A population-based analysis of mortality in patients with Turner syndrome and hypoplastic left heart syndrome using the Texas Birth Defects Registry.

    PubMed

    Lara, Diego A; Ethen, Mary K; Canfield, Mark A; Nembhard, Wendy N; Morris, Shaine A

    2017-01-01

    Hypoplastic left heart syndrome (HLHS) is strongly associated with Turner syndrome (TS); outcome data when these conditions coexist is sparse. We aimed to investigate long-term survival and causes of death in this population. The Texas Birth Defects Registry was queried for all live born infants with HLHS during 1999-2007. We used Kaplan-Meier and Cox regression analyses to compare survival among patients with HLHS with TS (HLHS/TS+) to patients who had HLHS without genetic disorders or extracardiac birth defects (HLHS/TS-). Of the 542 patients with HLHS, 11 had TS (2.0%), 71 had other extracardiac birth defects or genetic disorders, and 463 had neither. The median follow-up time was 4.2 y (interquartile range [IQR] 2.1-6.5). Comparing those with HLHS/TS+ to HLHS/TS-, 100% versus 35% were female (P < .001), and median birth weight was 2140 g (IQR 1809-2650) versus 3196 g (IQR 2807-3540, P < .001). Neonatal mortality was 36% in HLHS/TS+ versus 27% in HLHS/TS- (log rank = 0.431). Ten of the 11 TS+ patients died during the study period for cumulative mortality of 91% versus 50% (hazard ratio (HR) for TS+: 2.90, 95% CI 1.53-5.48). Six patients died prior to surgery, 5 underwent Stage 1 palliation (S1P), 3 died after S1P, 2 survived past S2P, and one of these died at age 19 mo. The underlying cause of death was listed as congenital heart disease on all the death certificates of HLHS/TS+ patients. In multivariable analysis controlling for low birth weight (<2500 g), TS remained associated with significantly increased cumulative mortality, although females without TS had higher mortality than males (HR for TS+ versus males: 2.42, 95% CI 1.24-4.73; HR for TS- females versus males: 1.41, 95% CI 1.08-1.83). TS with HLHS is associated with significant mortality. The increased mortality in females without documented TS calls to question if TS is undetected in a portion of females with HLHS. © 2016 Wiley Periodicals, Inc.

  9. Epidemiology of Lung Cancer

    PubMed Central

    Brock, Malcolm V.; Ford, Jean G.; Samet, Jonathan M.; Spivack, Simon D.

    2013-01-01

    Background: Ever since a lung cancer epidemic emerged in the mid-1900s, the epidemiology of lung cancer has been intensively investigated to characterize its causes and patterns of occurrence. This report summarizes the key findings of this research. Methods: A detailed literature search provided the basis for a narrative review, identifying and summarizing key reports on population patterns and factors that affect lung cancer risk. Results: Established environmental risk factors for lung cancer include smoking cigarettes and other tobacco products and exposure to secondhand tobacco smoke, occupational lung carcinogens, radiation, and indoor and outdoor air pollution. Cigarette smoking is the predominant cause of lung cancer and the leading worldwide cause of cancer death. Smoking prevalence in developing nations has increased, starting new lung cancer epidemics in these nations. A positive family history and acquired lung disease are examples of host factors that are clinically useful risk indicators. Risk prediction models based on lung cancer risk factors have been developed, but further refinement is needed to provide clinically useful risk stratification. Promising biomarkers of lung cancer risk and early detection have been identified, but none are ready for broad clinical application. Conclusions: Almost all lung cancer deaths are caused by cigarette smoking, underscoring the need for ongoing efforts at tobacco control throughout the world. Further research is needed into the reasons underlying lung cancer disparities, the causes of lung cancer in never smokers, the potential role of HIV in lung carcinogenesis, and the development of biomarkers. PMID:23649439

  10. Functional vascularized lung grafts for lung bioengineering

    PubMed Central

    Dorrello, N. Valerio; Guenthart, Brandon A.; O’Neill, John D.; Kim, Jinho; Cunningham, Katherine; Chen, Ya-Wen; Biscotti, Mauer; Swayne, Theresa; Wobma, Holly M.; Huang, Sarah X. L.; Snoeck, Hans-Willem; Bacchetta, Matthew; Vunjak-Novakovic, Gordana

    2017-01-01

    End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell–derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation. PMID:28875163

  11. Warning Signs of Lung Disease

    MedlinePlus

    ... Warning Signs of Lung Disease Warning Signs of Lung Disease A nagging cough or slight wheeze may ... prepare for you next office visit. Questions about Lung Health? Call our Lung HelpLine. Get free counseling ...

  12. Lung needle biopsy

    MedlinePlus

    ... if you have certain lung diseases such as emphysema. Usually, a collapsed lung after a biopsy does ... any type Bullae (enlarged alveoli that occur with emphysema) Cor pulmonale (condition that causes the right side ...

  13. Lungs and Respiratory System

    MedlinePlus

    ... Your 1- to 2-Year-Old Lungs and Respiratory System KidsHealth > For Parents > Lungs and Respiratory System A ... ll have taken at least 600 million breaths. Respiratory System Basics All of this breathing couldn't happen ...

  14. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  15. Lung cancer screening update

    PubMed Central

    Dhillon, Samjot Singh; Loewen, Gregory; Jayaprakash, Vijayvel; Reid, Mary E.

    2013-01-01

    Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer. PMID:23599684

  16. Interstitial Lung Disease

    MedlinePlus

    ... Critical Care & Sleep Medicine Interstitial Lung Disease Program Sarcoidosis Program Autoimmune Lung Center Rebecca C. Keith, MD, ... Syndromes Hypersensitivity Pneumonitis LAM Lupus Rheumatoid Arthritis (RA) Sarcoidosis Overview Scleroderma (SSC) Systemic Vasculitis Reasons to Visit ...

  17. Lung gallium scan

    MedlinePlus

    ... the lungs. This is most often due to sarcoidosis or a certain type of pneumonia. Normal Results ... it may mean any of the following problems: Sarcoidosis (disease in which inflammation occurs in the lungs ...

  18. Lung cancer prevention.

    PubMed

    Slatore, Christopher; Sockrider, Marianna

    2014-11-15

    Lung cancer is a common form of cancer.There are things you can do to lower your risk of lung cancer. Stop smoking tobacco. Ask your health care provider for help in quitting, including use of medicines to help with nicotine dependence. discuss with your healthcare provider,what you are taking or doing to decrease your risk for lung cancer

  19. Lungs and Respiratory System

    MedlinePlus

    ... A Week of Healthy Breakfasts Shyness Lungs and Respiratory System KidsHealth > For Teens > Lungs and Respiratory System A ... didn't breathe, you couldn't live. Lungs & Respiratory System Basics Each day we breathe about 20,000 ...

  20. The lung in space

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim

    2005-01-01

    The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

  1. The lung in space

    NASA Technical Reports Server (NTRS)

    Prisk, G. Kim

    2005-01-01

    The lung is exquisitely sensitive to gravity, which induces gradients in ventilation, blood flow, and gas exchange. Studies of lungs in microgravity provide a means of elucidating the effects of gravity. They suggest a mechanism by which gravity serves to match ventilation to perfusion, making for a more efficient lung than anticipated. Despite predictions, lungs do not become edematous, and there is no disruption to, gas exchange in microgravity. Sleep disturbances in microgravity are not a result of respiratory-related events; obstructive sleep apnea is caused principally by the gravitational effects on the upper airways. In microgravity, lungs may be at greater risk to the effects of inhaled aerosols.

  2. Advances in artificial lungs.

    PubMed

    Ota, Kei

    2010-04-01

    Artificial lungs have already been developed as complete artificial organs, and results of many investigations based on innovative concepts have been reported continuously. In open-heart surgery, artificial lungs are used for extracorporeal circulation to maintain gas exchange, and the commercial products currently available perform adequately, including providing for antithrombogenicity. However, patients after cardiopulmonary arrest or severe respiratory/circulatory failure have required long-term assist with extracorporeal membrane oxygenation (ECMO). The number of artificial lungs used for ECMO in those cases has shown significant growth in recent years. Therefore, it is expected that durability and antithrombogenicity will ensure the prolonged use of an artificial lung for several weeks or months. Furthermore, interests in research are shifting to use of oxygenators as a bridge to lung transplantation and an implantable artificial lung. This paper discusses recent advances in artificial lungs, focusing on the current state and on trends in research and development.

  3. [Lung cancer screening].

    PubMed

    Sánchez González, M

    2014-01-01

    Lung cancer is a very important disease, curable in early stages. There have been trials trying to show the utility of chest x-ray or computed tomography in Lung Cancer Screening for decades. In 2011, National Lung Screening Trial results were published, showing a 20% reduction in lung cancer mortality in patients with low dose computed tomography screened for three years. These results are very promising and several scientific societies have included lung cancer screening in their guidelines. Nevertheless we have to be aware of lung cancer screening risks, such as: overdiagnosis, radiation and false positive results. Moreover, there are many issues to be solved, including choosing the appropriate group to be screened, the duration of the screening program, intervals between screening and its cost-effectiveness. Ongoing trials will probably answer some of these questions. This article reviews the current evidence on lung cancer screening.

  4. Lung cancer in women

    PubMed Central

    Barrera-Rodriguez, Raúl; Morales-Fuentes, Jorge

    2012-01-01

    Recent biological advances in tumor research provide clear evidence that lung cancer in females is different from that in males. These differences appear to have a direct impact on the clinical presentation, histology, and outcomes of lung cancer. Women are more likely to present with lung adenocarcinoma, tend to receive a diagnosis at an earlier age, and are more likely to be diagnosed with localized disease. Women may also be more predisposed to molecular aberrations resulting from the carcinogenic effects of tobacco, but do not appear to be more susceptible than men to developing lung cancer. The gender differences found in female lung cancer make it mandatory that gender stratification is used in clinical trials in order to improve the survival rates of patients with lung cancer. PMID:28210127

  5. Six1 transcription factor is critical for coordination of epithelial, mesenchymal and vascular morphogenesis in the mammalian lung

    PubMed Central

    El-Hashash, Ahmed HK; Alam, Denise Al; Turcatel, Gianluca; Rogers, Orquidea; Li, Sean; Bellusci, Saverio; Warburton, David

    2011-01-01

    Six1 is a member of the six-homeodomain family of transcription factors. Six1 is expressed in multiple embryonic cell types and plays important roles in proliferation, differentiation and survival of precursor cells of different organs, yet its function during lung development was hitherto unknown. Herein we show that Six1−/− lungs are severely hypoplastic with greatly reduced epithelial branching and increased mesenchymal cellularity. Six1 is expressed at the distal epithelial tips of branching tubules as well as in the surrounding distal mesenchyme. Six1−/− lung epithelial cells show increased expression of differentiation markers, but loss of progenitor cell markers. Six1 overexpression in MLE15 lung epithelial cells in vitro inhibited cell differentiation, but increases the expression of progenitor cell markers. In addition, Six1−/− embryos and newborn mice exhibit mesenchymal overproliferation, decreased Fgf10 expression and severe defects in the smooth muscle component of the bronchi and major pulmonary vessels. These defects lead to rupture of major vessels in mutant lungs after birth. Treatment of Six1−/− epithelial explants in culture with recombinant Fgf10 protein restores epithelial branching. As Shh expression is abnormally increased in Six1−/− lungs, we also treated mutant mesenchymal explants with recombinant Shh protein and found that these explants were competent to respond to Shh and continued to grow in culture. Furthermore, inhibition of Shh signaling with cyclopamine stimulated Six1−/− lungs to grow and branch in culture. This study provides the first evidence for the requirement of Six1 in coordinating Shh-Fgf10 signaling in embryonic lung to ensure proper levels of proliferation and differentiation along the proximodistal axis of epithelial, mesenchymal and endothelial cells. These findings uncover novel and essential functions for Six1 as a critical coordinator of Shh- Fgf10 signaling during embryonic lung development

  6. Pediatric Lung Transplantation.

    PubMed

    Sweet, Stuart C

    2017-06-01

    Pediatric lung transplant is a viable option for treatment of end-stage lung disease in children, with > 100 pediatric lung transplants reported to the Registry of the International Society of Heart and Lung Transplantation each year. Long-term success is limited by availability of donor organs, debilitation as a result of chronic disease, impaired mucus clearance resulting from both surgical and pharmacologic interventions, increased risk for infection resulting from immunosuppression, and most importantly late complications, such as chronic lung allograft dysfunction. Opportunities for investigation and innovation remain in all of these domains: (1) Ex vivo lung perfusion is a promising technology with the potential for increasing the lung donor pool, (2) evolving extracorporeal support strategies coupled with effective rehabilitation will effectively bridge critically ill patients to transplant, and most importantly, (3) research efforts intended to increase our understanding of the underlying mechanisms of chronic lung allograft dysfunction will ultimately lead to the development of effective therapies to prevent or treat the variety of chronic lung allograft dysfunction presentations. Copyright © 2017 by Daedalus Enterprises.

  7. Your Lungs and Respiratory System

    MedlinePlus

    ... Lifesaver Kids Talk About: Coaches Your Lungs & Respiratory System KidsHealth > For Kids > Your Lungs & Respiratory System Print ... its regular size. You've just felt the power of your lungs! continue A Look Inside the ...

  8. 6 Common Cancers - Lung Cancer

    MedlinePlus

    ... Home Current Issue Past Issues 6 Common Cancers - Lung Cancer Past Issues / Spring 2007 Table of Contents ... for Desperate Housewives. (Photo ©2005 Kathy Hutchins / Hutchins) Lung Cancer Lung cancer causes more deaths than the ...

  9. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  10. Interstitial lung disease - adults - discharge

    MedlinePlus

    ... lung disease Pulmonary alveolar proteinosis Rheumatoid lung disease Sarcoidosis Patient Instructions Eating extra calories when sick - adults ... team. Related MedlinePlus Health Topics Interstitial Lung Diseases Sarcoidosis Browse the Encyclopedia A.D.A.M., Inc. ...

  11. Lung protective strategies in anaesthesia.

    PubMed

    Kilpatrick, B; Slinger, P

    2010-12-01

    Patients are at risk for several types of lung injury in the perioperative period including atelectasis, pneumonia, pneumothorax, acute lung injury, and acute respiratory distress syndrome. Anaesthetic management can cause, exacerbate, or ameliorate these injuries. This review examines the effects of perioperative mechanical ventilation and its role in ventilator-induced lung injury. Lung protective ventilatory strategies to specific clinical situations such as cardiopulmonary bypass and one-lung ventilation along with newer novel lung protective strategies are discussed.

  12. Lung alveolar epithelium and interstitial lung disease.

    PubMed

    Corvol, Harriet; Flamein, Florence; Epaud, Ralph; Clement, Annick; Guillot, Loic

    2009-01-01

    Interstitial lung diseases (ILDs) comprise a group of lung disorders characterized by various levels of inflammation and fibrosis. The current understanding of the mechanisms underlying the development and progression of ILD strongly suggests a central role of the alveolar epithelium. Following injury, alveolar epithelial cells (AECs) may actively participate in the restoration of a normal alveolar architecture through a coordinated process of re-epithelialization, or in the development of fibrosis through a process known as epithelial-mesenchymal transition (EMT). Complex networks orchestrate EMT leading to changes in cell architecture and behaviour, loss of epithelial characteristics and gain of mesenchymal properties. In the lung, AECs themselves may serve as a source of fibroblasts and myofibroblasts by acquiring a mesenchymal phenotype. This review covers recent knowledge on the role of alveolar epithelium in the pathogenesis of ILD. The mechanisms underlying disease progression are discussed, with a main focus on the apoptotic pathway, the endoplasmic reticulum stress response and the developmental pathway.

  13. Lung diffusion testing

    MedlinePlus

    ... the blood from the lungs, and to allow carbon dioxide to "diffuse" from the blood into the lungs. How the Test is Performed You breathe in (inhale) air containing a very small amount of carbon monoxide and a tracer gas, such as methane ...

  14. Lung Cancer Indicators Recurrence

    Cancer.gov

    This study describes prognostic factors for lung cancer spread and recurrence, as well as subsequent risk of death from the disease. The investigators observed that regardless of cancer stage, grade, or type of lung cancer, patients in the study were more

  15. Artificial lung: current perspectives.

    PubMed

    Go, T; Macchiarini, P

    2008-10-01

    While the number of the patients suffering from end-stage pulmonary disease has been increasing, the most common treatment for this entity remains mechanical ventilation that entails the risks of lung damage by itself. Although the lung protective strategy for the prevention of further damage to the lung tissue has been elucidated and performed, mechanical ventilation alone as the management tactic coping with the patients of acute respiratory distress syndrome, chronic respiratory failure and lung transplantations has been a frustrated scenario. Extracorporeal membrane oxygenation or extracorporeal lung assist have been applied to these patients with occasional success, but it always accompanies difficulties such as multiple blood transfusion, labor intensity, technically complexity and tendency to infection. In contrast to advances in the development of cardiac or renal support systems for adults, the development of extra-, para- and intracorporeal mechanical systems for acute or chronic lung respiratory failure has logged far behind. It has been mostly due to the lack of the capable technologies. Entering 21st century with advent of new technology especially invention of the low resistance oxygenator, the developments of artificial lungs have entered the new stage. In this report current status of the artificial lungs will be reviewed.

  16. Lung Diseases and Conditions

    MedlinePlus

    ... Explore How the Lungs Work What Are... The Respiratory System What Happens When You Breathe What Controls Your Breathing Lung Diseases & Conditions Clinical Trials Links Related Topics Asthma Bronchitis COPD How the Heart Works Respiratory Failure Send a link to NHLBI to someone ...

  17. Lycopene and Lung Cancer

    USDA-ARS?s Scientific Manuscript database

    Although epidemiological studies have shown dietary intake of lycopene is associated with decreased risk of lung cancer, the effect of lycopene on lung carcinogenesis has not been well studied. A better understanding of lycopene metabolism and the mechanistic basis of lycopene chemoprevention must ...

  18. Indium lung disease.

    PubMed

    Cummings, Kristin J; Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-Long; Harley, Russell A; Roggli, Victor L; Hebisawa, Akira; Tallaksen, Robert J; Trapnell, Bruce C; Day, Gregory A; Saito, Rena; Stanton, Marcia L; Suarthana, Eva; Kreiss, Kathleen

    2012-06-01

    Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies.

  19. Lung transplant infection.

    PubMed

    Burguete, Sergio R; Maselli, Diego J; Fernandez, Juan F; Levine, Stephanie M

    2013-01-01

    Lung transplantation has become an accepted therapeutic procedure for the treatment of end-stage pulmonary parenchymal and vascular disease. Despite improved survival rates over the decades, lung transplant recipients have lower survival rates than other solid organ transplant recipients. The morbidity and mortality following lung transplantation is largely due to infection- and rejection-related complications. This article will review the common infections that develop in the lung transplant recipient, including the general risk factors for infection in this population, and the most frequent bacterial, viral, fungal and other less frequent opportunistic infections. The epidemiology, diagnosis, prophylaxis, treatment and outcomes for the different microbial pathogens will be reviewed. The effects of infection on lung transplant rejection will also be discussed.

  20. Immunotherapy in Lung Cancer.

    PubMed

    Castellanos, Emily H; Horn, Leora

    2016-01-01

    Lung cancer has not traditionally been viewed as an immune-responsive tumor. However, it is becoming evident that tumor-induced immune suppression is vital to malignant progression. Immunotherapies act by enhancing the patient's innate immune response and hold promise for inducing long-term responses in select patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Immune checkpoint inhibitors, in particular, inhibitors to cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) and programmed death receptor ligand 1 (PD-L1) have shown promise in early studies and are currently in clinical trials in both small cell lung cancer and non-small cell lung cancer patients. Two large randomized phase III trials recently demonstrated superior overall survival (OS) in patients treated with anti-PD-1 therapy compared to chemotherapy in the second-line setting.

  1. Lung cancer screening.

    PubMed

    Tanoue, Lynn T; Tanner, Nichole T; Gould, Michael K; Silvestri, Gerard A

    2015-01-01

    The United States Preventive Services Task Force recommends lung cancer screening with low-dose computed tomography (LDCT) in adults of age 55 to 80 years who have a 30 pack-year smoking history and are currently smoking or have quit within the past 15 years. This recommendation is largely based on the findings of the National Lung Screening Trial. Both policy-level and clinical decision-making about LDCT screening must consider the potential benefits of screening (reduced mortality from lung cancer) and possible harms. Effective screening requires an appreciation that screening should be limited to individuals at high risk of death from lung cancer, and that the risk of harm related to false positive findings, overdiagnosis, and unnecessary invasive testing is real. A comprehensive understanding of these aspects of screening will inform appropriate implementation, with the objective that an evidence-based and systematic approach to screening will help to reduce the enormous mortality burden of lung cancer.

  2. Lung cancer - non-small cell

    MedlinePlus

    Cancer - lung - non-small cell; Non-small cell lung cancer; NSCLC; Adenocarcinoma - lung; Squamous cell carcinoma - lung ... Smoking causes most cases (around 90%) of lung cancer. The risk depends on the number of cigarettes ...

  3. Occupational lung cancer

    SciTech Connect

    Coultas, D.B.; Samet, J.M. )

    1992-06-01

    The overall importance of occupational agents as a cause of lung cancer has been a controversial subject since the 1970s. A federal report, released in the late 1970s, projected a surprisingly high burden of occupational lung cancer; for asbestos and four other agents, from 61,000 to 98,000 cases annually were attributed to these agents alone. Many estimates followed, some much more conservative. For example, Doll and Peto estimated that 15% of lung cancer in men and 5% in women could be attributed to occupational exposures. A number of population-based case-control studies also provide relevant estimates. In a recent literature review, Vineis and Simonato cited attributable risk estimates for occupation and lung cancer that ranged from 4% to 40%; for asbestos alone, the estimates ranged from 1% to 5%. These estimates would be expected to vary across locations and over time. Nevertheless, these recent estimates indicate that occupation remains an important cause of lung cancer. Approaches to Prevention. Prevention of lung cancer mortality among workers exposed to agents or industrial processes that cause lung cancer may involve several strategies, including eliminating or reducing exposures, smoking cessation, screening, and chemo-prevention. For example, changes in industrial processes that have eliminated or reduced exposures to chloromethyl ethers and nickel compounds have provided evidence of reduced risk of lung cancer following these changes. Although occupational exposures are important causes of lung cancer, cigarette smoking is the most important preventable cause of lung cancer. For adults, the work site offers an important location to target smoking cessation efforts. In fact, the work site may be the only place to reach many smokers.

  4. Estimation of Lung Ventilation

    NASA Astrophysics Data System (ADS)

    Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

    Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

  5. Lung Cancer Screening Update.

    PubMed

    Ruchalski, Kathleen L; Brown, Kathleen

    2016-07-01

    Since the release of the US Preventive Services Task Force and Centers for Medicare and Medicaid Services recommendations for lung cancer screening, low-dose chest computed tomography screening has moved from the research arena to clinical practice. Lung cancer screening programs must reach beyond image acquisition and interpretation and engage in a multidisciplinary effort of clinical shared decision-making, standardization of imaging and nodule management, smoking cessation, and patient follow-up. Standardization of radiologic reports and nodule management will systematize patient care, provide quality assurance, further reduce harm, and contain health care costs. Although the National Lung Screening Trial results and eligibility criteria of a heavy smoking history are the foundation for the standard guidelines for low-dose chest computed tomography screening in the United States, currently only 27% of patients diagnosed with lung cancer would meet US lung cancer screening recommendations. Current and future efforts must be directed to better delineate those patients who would most benefit from screening and to ensure that the benefits of screening reach all socioeconomic strata and racial and ethnic minorities. Further optimization of lung cancer screening program design and patient eligibility will assure that lung cancer screening benefits will outweigh the potential risks to our patients.

  6. Lung Transplantation for Scleroderma-related Lung Disease

    PubMed Central

    Richardson, Claire B.; Singer, Jonathan P

    2014-01-01

    Lung transplantation for scleroderma-related lung disease is controversial due to extra-pulmonary organ involvement that may threaten allograft and patient survival after transplant surgery. Despite concerns, several lung transplant programs do offer lung transplantation to patients with scleroderma-related lung disease. In this review, we evaluate the scleroderma-related extra-pulmonary organ involvement that may result in poorer outcomes after lung transplantation as well as the existing evidence on survival, freedom from bronchiolitis obliterans syndrome (BOS), and other important clinical outcomes after lung transplantation. Among the nine studies reviewed, comprising 226 subjects, survival and freedom from BOS appears to be similar for subjects undergoing lung transplantation for scleroderma compared to non-scleroderma lung diseases. Although scleroderma is a systemic disease with several unique potential threats to allograft and patient survival, lung transplantation appears to be a reasonable intervention for this patient population. PMID:27833787

  7. Bioengineering Lungs for Transplantation.

    PubMed

    Gilpin, Sarah E; Charest, Jonathan M; Ren, Xi; Ott, Harald C

    2016-05-01

    Whole lung extracellular matrix scaffolds can be created by perfusion of cadaveric organs with decellularizing detergents, providing a platform for organ regeneration. Lung epithelial engineering must address both the proximal airway cells that function to metabolize toxins and aid mucociliary clearance and the distal pneumocytes that facilitate gas exchange. Engineered pulmonary vasculature must support in vivo blood perfusion with low resistance and intact barrier function and be antithrombotic. Repopulating the native lung matrix with sufficient cell numbers in appropriate anatomic locations is required to enable organ function.

  8. Microgravity and the lung

    NASA Technical Reports Server (NTRS)

    West, John B.

    1991-01-01

    Results are presented from studies of the effect of microgravity on the lungs of rats flown on the Cosmos 2044 mission, and from relevant laboratory experiments. The effects of microgravity fall into five categories: topographical structure and function, the lung volumes and mechanics, the intrathoracic blood pressures and volumes, the pulmonary deposition of aerosol, and denitrogenaton during EVA. The ultrastructure of the left lungs of rats flown for 14 days on the Cosmos 2044 spacecraft and that of some tail-suspended rats disclosed presence of red blood cells in the alveolar spaces, indicating that pulmonary hemorrhage and pulmonary edema occurred in these rats. Possible causes for this phenomenon are discussed.

  9. Lung Cancer Screening.

    PubMed

    Hoffman, Richard M; Sanchez, Rolando

    2017-07-01

    Lung cancer is the leading cause of cancer death in the United States. More than 80% of these deaths are attributed to tobacco use, and primary prevention can effectively reduce the cancer burden. The National Lung Screening Trial showed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in high-risk patients by 20% compared with chest radiography. The US Preventive Services Task Force recommends annual LDCT screening for persons aged 55 to 80 years with a 30-pack-year smoking history, either currently smoking or having quit within 15 years. Published by Elsevier Inc.

  10. The lung communication network.

    PubMed

    Losa, Davide; Chanson, Marc

    2015-08-01

    The different types of cells in the lung, from the conducting airway epithelium to the alveolar epithelium and the pulmonary vasculature, are interconnected by gap junctions. The specific profile of gap junction proteins, the connexins, expressed in these different cell types forms compartments of intercellular communication that can be further shaped by the release of extracellular nucleotides via pannexin1 channels. In this review, we focus on the physiology of connexins and pannexins and describe how this lung communication network modulates lung function and host defenses in conductive and respiratory airways.

  11. Cyclophosphamide in diffuse lung damage.

    PubMed

    Musiatowicz, B; Sulkowska, M; Sulik, M; Famulski, W; Dziecioł, J; Sobaniec-Lotowska, M; Baltaziak, M; Arciuch, L; Rółkowski, R; Jabłońska, E

    1997-01-01

    Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

  12. Familial risk for lung cancer

    PubMed Central

    Kanwal, Madiha; Ding, Xiao-Ji; Cao, Yi

    2017-01-01

    Lung cancer, which has a low survival rate, is a leading cause of cancer-associated mortality worldwide. Smoking and air pollution are the major causes of lung cancer; however, numerous studies have demonstrated that genetic factors also contribute to the development of lung cancer. A family history of lung cancer increases the risk for the disease in both smokers and never-smokers. This review focuses on familial lung cancer, in particular on the familial aggregation of lung cancer. The development of familial lung cancer involves shared environmental and genetic factors among family members. Familial lung cancer represents a good model for investigating the association between environmental and genetic factors, as well as for identifying susceptibility genes for lung cancer. In addition, studies on familial lung cancer may help to elucidate the etiology and mechanism of lung cancer, and may identify novel biomarkers for early detection and diagnosis, targeted therapy and improved prevention strategies. This review presents the aetiology and molecular biology of lung cancer and then systematically introduces and discusses several aspects of familial lung cancer, including the characteristics of familial lung cancer, population-based studies on familial lung cancer and the genetics of familial lung cancer. PMID:28356926

  13. Novel Mutations in the NKX2.1 gene and the PAX8 gene in a Boy with Brain-Lung-Thyroid Syndrome.

    PubMed

    Hermanns, Pia; Kumorowicz-Czoch, Małgorzata; Grasberger, Helmut; Refetoff, Samuel; Pohlenz, Joachim

    2017-09-27

    Objective To elucidate the molecular mechanism which causes thyroid dysgenesis (TD) in a boy with brain-lung-thyroid syndrome. Design, patients, measurements We describe a patient with TD, respiratory disease and cerebral palsy who is heterozygous for mutations in two different genes, the PAX8 (p.E234K) and the NKX2.1 (p.A329GfsX108). In vitro studies were performed to functionally characterize these mutations. Congenital hypothyroidism (CH) was identified by neonatal screening associated with a hypoplastic thyroid gland. Postpartum he developed a brain-lung-thyroid syndrome with severe respiratory failure, symptomatic epilepsy and a considerable psychomotor retardation. The DNA-binding capability and the transcriptional activity of the two mutated transcription factors were investigated in vitro. Results The NKX2.1 mutation did not show any transcriptional activity and had almost no DNA-binding. The PAX8 mutation was normally located to the nucleus and showed a normal transactivation and a normal binding to the known downstream targets. Conclusions The molecular defect explaining the phenotype of brain-lung-thyroid syndrome was identified. To what extent the PAX8 mutation contributes to the phenotype needs to be further investigated. We recommend to screen patients with CH and TD for mutations in all known TD candidate genes. © Georg Thieme Verlag KG Stuttgart · New York.

  14. What Are the Lungs?

    MedlinePlus

    ... oxygen from the air. They also help remove carbon dioxide (a waste gas that can be toxic) from ... The lungs' intake of oxygen and removal of carbon dioxide is called gas exchange. Gas exchange is part ...

  15. Women and Lung Cancer

    MedlinePlus

    ... Horrigan Conners Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital, Harvard Medical School, April, ... Lung Cancer in Women: The Differences in Epidemiology, Biology and Treatment Outcomes, Maria Patricia Rivera MD Expert ...

  16. Lung Carcinoid Tumor: Surgery

    MedlinePlus

    ... the sleeve above and below the stain and sewing the cuff back onto the shortened sleeve. A ... because it requires a great deal of technical skill. Possible risks and side effects of lung surgery ...

  17. Justice and lung cancer.

    PubMed

    Wilson, Aaron

    2013-04-01

    Lung cancer is the leading cause of cancer deaths, yet research funding is by far the lowest for lung cancer than for any other cancer compared with respective death rates. Although this discrepancy should appear alarming, one could argue that lung cancer deserves less attention because it is more attributable to poor life choices than other common cancers. Accordingly, the general question that I ask in this article is whether victims of more avoidable diseases, such as lung cancer, deserve to have their needs taken into less consideration than those of less avoidable diseases, on the grounds of either retributive or distributive justice. Such unequal treatment may be the "penalty" one incurs for negligent or reckless behavior. However, I hope to show that such unequal treatment cannot be supported by any coherent accounts of retributive or distributive justice.

  18. Protecting Your Lungs

    MedlinePlus

    ... That Can Damage Your Lungs Secondhand smoke, outdoor air pollution , chemicals in the home and workplace, and radon ... nothing else matters ® . Help us fight to reduce pollution in the air we breathe. Donate

  19. Interstitial lung disease

    MedlinePlus

    ... screened for lung disease. These jobs include coal mining, sand blasting, and working on a ship. Treatment ... Traveling with breathing problems Using oxygen at home Images Clubbing Coal workers pneumoconiosis - stage II Coal workers ...

  20. Abscess in the Lungs

    MedlinePlus

    ... a sample of sputum and try to grow (culture) the organism causing the abscess, but this test ... obtain samples of lung secretions or tissue for culture if, for example, Antibiotics seem ineffective Obstruction of ...

  1. Lung disease - resources

    MedlinePlus

    ... gov/health/dci/Diseases/Asthma/Asthma_WhatIs.html Emphysema/COPD (Chronic Obstructive Pulmonary Disease): COPD Foundation -- www.copdfoundation.org National Emphysema Foundation -- www.emphysemafoundation.org National Heart, Lung, and ...

  2. Lung surgery - discharge

    MedlinePlus

    ... Lung biopsy - discharge; Thoracoscopy - discharge; Video-assisted thoracoscopic surgery - discharge; VATS - discharge ... milk) for 2 weeks after video-assisted thoracoscopic surgery and 6 to 8 weeks after open surgery. ...

  3. Biomarkers of Lung Injury

    EPA Science Inventory

    Unlike the hepatic, cardiovascular, nervous, or excretory organ systems, where there .ls a strong contribution of host factors or extracellular biochemical milieu in causing organ damage, the causes of lung injuries and subsequent diseases are primarily from direct environmental ...

  4. Immunotherapy for lung cancer.

    PubMed

    Steven, Antonius; Fisher, Scott A; Robinson, Bruce W

    2016-07-01

    Treatment of lung cancer remains a challenge, and lung cancer is still the leading cause of cancer-related mortality. Immunotherapy has previously failed in lung cancer but has recently emerged as a very effective new therapy, and there is now growing worldwide enthusiasm in cancer immunotherapy. We summarize why immune checkpoint blockade therapies have generated efficacious and durable responses in clinical trials and why this has reignited interest in this field. Cancer vaccines have also been explored in the past with marginal success. Identification of optimal candidate neoantigens may improve cancer vaccine efficacy and may pave the way to personalized immunotherapy, alone or in combination with other immunotherapy such as immune checkpoint blockade. Understanding the steps in immune recognition and eradication of cancer cells is vital to understanding why previous immunotherapies failed and how current therapies can be used optimally. We hold an optimistic view for the future prospect in lung cancer immunotherapy.

  5. Open lung biopsy

    MedlinePlus

    ... tissues) Granulomatosis with polyangiitis (inflammation of the blood vessels) Pulmonary hypertension (high blood pressure in the arteries of the lungs) Risks There is a slight chance of: Air leak Excess blood loss Infection Injury to the ...

  6. Biomarkers of Lung Injury

    EPA Science Inventory

    Unlike the hepatic, cardiovascular, nervous, or excretory organ systems, where there .ls a strong contribution of host factors or extracellular biochemical milieu in causing organ damage, the causes of lung injuries and subsequent diseases are primarily from direct environmental ...

  7. Endocardial Fibroelastosis of the Left Ventricle Affects Right Ventricular Performance in Fetuses with Hypoplastic Left Heart Syndrome: A Prospective Study Using M-Mode, PW- and Tissue Doppler Techniques.

    PubMed

    Graupner, Oliver; Enzensberger, Christian; Wieg, Larissa; Degenhardt, Jan; Wolter, Aline; Khalil, Markus; Schranz, Dietmar; Yerebakan, Can; Doelle, Astrid; Herrmann, Johannes; Axt-Fliedner, Roland

    2017-07-06

    Purpose Myocardial function (MF) of the systemic right ventricle (RV) influences the postnatal course of neonates with hypoplastic left heart syndrome (HLHS). Our study examines whether the presence of endocardial fibroelastosis of the left ventricle (LV EFE) influences MF of the RV in HLHS fetuses. Materials and Methods A prospective study was conducted including 10 controls (group 1), 10 HLHS fetuses with (group 2) and 10 without LV EFE (group 3) - all matched for gestational age. M-mode was used to assess tricuspid plane systolic excursion (TAPSE) and the shortening fraction (SF). PW-Doppler-derived and PW-TDI-derived velocities were assessed. E/A, E/e', e'/a' ratios and the myocardial performance index (mpi') were calculated. Results The examination of MF revealed significantly lower s' velocities (p < 0.05) and higher values for SF in group 2 compared to group 3. e'/a' ratio, et' (ejection time), E wave velocity, E/e' and SF showed significantly higher values in group 2 compared to group 1. In group 2 a' velocity increased significantly over gestational age. In group 3 but not in group 2, TAPSE increased during gestation. Conclusion These significant differences in MF between the groups might lend support to the notion of negative ventricular-ventricular interaction in the case of HLHS with LV EFE possibly influencing surgical outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Lung Cancer Biomarkers.

    PubMed

    I, Hoseok; Cho, Je-Yoel

    2015-01-01

    Lung cancer is the most frequently occurring cancer in the world and continually leads in mortality among cancers. The overall 5-year survival rate for lung cancer has risen only 4% (from 12% to 16%) over the past 4 decades, and late diagnosis is a major obstacle in improving lung cancer prognosis. Survival of patients undergoing lung resection is greater than 80%, suggesting that early detection and diagnosis of cancers before they become inoperable and lethal will greatly improve mortality. Lung cancer biomarkers can be used for screening, detection, diagnosis, prognosis, prediction, stratification, therapy response monitoring, and so on. This review focuses on noninvasive diagnostic and prognostic biomarkers. For that purpose, our discussion in this review will focus on biological fluid-based biomarkers. The body fluids include blood (serum or plasma), sputum, saliva, BAL, pleural effusion, and VOC. Since it is rich in different cellular and molecular elements and is one of the most convenient and routine clinical procedures, serum or plasma is the main source for the development and validation of many noninvasive biomarkers. In terms of molecular aspects, the most widely validated ones are proteins, some of which are used in the clinical sector, though in limited accessory purposes. We will also discuss the lung cancer (protein) biomarkers in clinical trials and currently in the validation phase with hundreds of samples. After proteins, we will discuss microRNAs, methylated DNA, and circulating tumor cells, which are being vigorously developed and validated as potential lung cancer biomarkers. The main aim of this review is to provide researchers and clinicians with an understanding of the potential noninvasive lung cancer biomarkers in biological fluids that have recently been discovered.

  9. Lung epinephrine synthesis

    SciTech Connect

    Kennedy, B.; Elayan, H.; Ziegler, M.G. )

    1990-04-01

    We studied in vitro and in vivo epinephrine (E) synthesis by rat lung. Nine days after removal of the adrenal medullas, circulating E was reduced to 7% of levels found in sham-operated rats but 30% of lung E remained. Treatment of demedullated rats with 6 hydroxydopamine plus reserpine did not further reduce lung E. In the presence of S-(3H)adenosylmethionine lung homogenates readily N-methylated norepinephrine (NE) to form (3H)E. The rate of E synthesis by lung homogenates was progressively more rapid with increasing NE up to a concentration of 3 mM, above which it declined. The rate of E formation was optimal at an incubation pH of 8 and at temperatures of approximately 55 degrees C. We compared the E-forming enzyme(s) of lung homogenates with those of adrenal and cardiac ventricle. The adrenal contains mainly phenylethanolamine N-methyltransferase (PNMT), which is readily inhibited by SKF 29661 and methylates dopamine (DA) very poorly. Cardiac ventricles contain mainly nonspecific N-methyltransferase (NMT), which is poorly inhibited by SKF 29661 and readily methylates both DA and NE. Lung homogenates were inhibited by SKF 29661 about half as well as adrenal but more than ventricle. We used the rate of E formation from NE as an index of PNMT-like activity and deoxyepinephrine synthesis from DA as an index of NMT-like activity. PNMT and NMT activity in rat lung homogenates were not correlated with each other, displayed different responses to change in temperature, and were affected differently by glucocorticoids.

  10. Indium Lung Disease

    PubMed Central

    Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

    2012-01-01

    Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

  11. Lung Epithelial Progenitor Cells

    PubMed Central

    Rawlins, Emma L.

    2008-01-01

    The current enthusiasm for stem cell research stems from the hope that damaged or diseased tissues may one day be repaired through the manipulation of endogenous or exogenous stem cells. The postnatal human respiratory system is highly accessible and provides unique opportunities for the application of such techniques. Several putative adult lung epithelial stem cells have been identified in the mouse model system. However, their in vivo capabilities to contribute to different lineages, and their control mechanisms, remain unclear. If stem cell–based therapies are to be successful in the lung, it is vitally important that we understand the normal behavior of adult lung stem cells, and how this is regulated. Lung embryonic progenitor cells are much better defined and characterized than their adult counterparts. Moreover, experiments on a variety of developing tissues are beginning to uncover general mechanisms by which embryonic progenitors influence final organ size and structure. This provides a framework for the study of lung embryonic progenitor cells, facilitating experimental design and interpretation. A similar approach to investigating adult lung stem cells could produce rapid advances in the field. PMID:18684716

  12. Lung Parenchymal Mechanics

    PubMed Central

    Suki, Béla; Stamenovic, Dimitrije; Hubmayr, Rolf

    2014-01-01

    The lung parenchyma comprises a large number of thin-walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This article focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed. PMID:23733644

  13. Pediatric lobar lung transplantation.

    PubMed

    Watson, T J; Starnes, V A

    1996-07-01

    The disparity between available donors and potential recipients of lung transplants has demanded a certain degree of flexibility on the part of transplantation surgeons. Marginal donors are now being used more frequently, and downsizing lungs from larger donors to fit into small recipients is quite common. In some instances, particularly in the circumstances of children, a single lobe from a much larger donor may serve very well as an entire lung in the recipient. Although either the upper or lower lobes from either side may be used, the lower lobes, especially the left, are better suited for this purpose because of the anatomy of the arterial, venous, and bronchial systems. As an extension of this concept, living-donor lung transplantation is now an accepted practice in carefully selected patients. Most children are best treated with bilateral lobar transplantation, particularly when cystic fibrosis is the indication. For living-donor transplantation, this obviously involves engaging two willing donors able to pass a rigorous physical and psychological evaluation. Although the recipients are generally sicker than the average cadaveric lung transplant recipient, early results to date have been similar to those receiving cadaveric lungs. In this article, we will describe our experience with this procedure, including the evaluation process, the technical aspects of the donor and recipient operations, and the results in the donors and recipients.

  14. Lung parenchymal mechanics.

    PubMed

    Suki, Béla; Stamenović, Dimitrije; Hubmayr, Rolf

    2011-07-01

    The lung parenchyma comprises a large number of thin-walled alveoli, forming an enormous surface area, which serves to maintain proper gas exchange. The alveoli are held open by the transpulmonary pressure, or prestress, which is balanced by tissues forces and alveolar surface film forces. Gas exchange efficiency is thus inextricably linked to three fundamental features of the lung: parenchymal architecture, prestress, and the mechanical properties of the parenchyma. The prestress is a key determinant of lung deformability that influences many phenomena including local ventilation, regional blood flow, tissue stiffness, smooth muscle contractility, and alveolar stability. The main pathway for stress transmission is through the extracellular matrix. Thus, the mechanical properties of the matrix play a key role both in lung function and biology. These mechanical properties in turn are determined by the constituents of the tissue, including elastin, collagen, and proteoglycans. In addition, the macroscopic mechanical properties are also influenced by the surface tension and, to some extent, the contractile state of the adherent cells. This chapter focuses on the biomechanical properties of the main constituents of the parenchyma in the presence of prestress and how these properties define normal function or change in disease. An integrated view of lung mechanics is presented and the utility of parenchymal mechanics at the bedside as well as its possible future role in lung physiology and medicine are discussed.

  15. Live Imaging of the Lung

    PubMed Central

    Looney, Mark R.; Bhattacharya, Jahar

    2015-01-01

    Live lung imaging has spanned the discovery of capillaries in the frog lung by Malpighi to the current use of single and multiphoton imaging of intravital and isolated perfused lung preparations incorporating fluorescent molecular probes and transgenic reporter mice. Along the way, much has been learned about the unique microcirculation of the lung, including immune cell migration and the mechanisms by which cells at the alveolar-capillary interface communicate with each other. In this review, we highlight live lung imaging techniques as applied to the role of mitochondria in lung immunity, mechanisms of signal transduction in lung compartments, studies on the composition of alveolar wall liquid, and neutrophil and platelet trafficking in the lung under homeostatic and inflammatory conditions. New applications of live lung imaging and the limitations of current techniques are discussed. PMID:24245941

  16. Screening for Lung Cancer

    PubMed Central

    Mazzone, Peter J.; Naidich, David P.; Bach, Peter B.

    2013-01-01

    Background: Lung cancer is by far the major cause of cancer deaths largely because in the majority of patients it is at an advanced stage at the time it is discovered, when curative treatment is no longer feasible. This article examines the data regarding the ability of screening to decrease the number of lung cancer deaths. Methods: A systematic review was conducted of controlled studies that address the effectiveness of methods of screening for lung cancer. Results: Several large randomized controlled trials (RCTs), including a recent one, have demonstrated that screening for lung cancer using a chest radiograph does not reduce the number of deaths from lung cancer. One large RCT involving low-dose CT (LDCT) screening demonstrated a significant reduction in lung cancer deaths, with few harms to individuals at elevated risk when done in the context of a structured program of selection, screening, evaluation, and management of the relatively high number of benign abnormalities. Whether other RCTs involving LDCT screening are consistent is unclear because data are limited or not yet mature. Conclusions: Screening is a complex interplay of selection (a population with sufficient risk and few serious comorbidities), the value of the screening test, the interval between screening tests, the availability of effective treatment, the risk of complications or harms as a result of screening, and the degree with which the screened individuals comply with screening and treatment recommendations. Screening with LDCT of appropriate individuals in the context of a structured process is associated with a significant reduction in the number of lung cancer deaths in the screened population. Given the complex interplay of factors inherent in screening, many questions remain on how to effectively implement screening on a broader scale. PMID:23649455

  17. Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4

    PubMed Central

    Strassner, James P.

    2013-01-01

    T cell trafficking into the lung is critical for lung immunity, but the mechanisms that mediate T cell lung homing are not well understood. Here, we show that lung dendritic cells (DCs) imprint T cell lung homing, as lung DC–activated T cells traffic more efficiently into the lung in response to inhaled antigen and at homeostasis compared with T cells activated by DCs from other tissues. Consequently, lung DC–imprinted T cells protect against influenza more effectively than do gut and skin DC–imprinted T cells. Lung DCs imprint the expression of CCR4 on T cells, and CCR4 contributes to T cell lung imprinting. Lung DC–activated, CCR4-deficient T cells fail to traffic into the lung as efficiently and to protect against influenza as effectively as lung DC–activated, CCR4-sufficient T cells. Thus, lung DCs imprint T cell lung homing and promote lung immunity in part through CCR4. PMID:23960189

  18. Adaptive lung ventilation.

    PubMed

    Linton, D M

    2001-09-01

    Adaptive lung ventilation (ALV) is a method of closed-loop mechanical ventilation analogous to modern closed-loop technology in aviation such as the autopilot and automatic landing system. The algorithm of the controller of ALV is designed to automatically provide pressure-controlled synchronized intermittent mandatory ventilation (P-SIMV) and weaning as individually required in any clinical situation. The synchronized pressure limited breaths constantly adapt to the patient requirements to encourage optimal alveolar ventilation with minimal adverse physiological disturbance and timely weaning. The ease of application, efficiency, and safety of the first ALV controllers have been demonstrated in lung models, in patients with normal lungs undergoing general anesthesia, in patients requiring unusual positioning, in transition to and from one-lung anesthesia, and in long-term ventilation of patients with various lung pathologies and in weaning patients who have restrictive or obstructive pulmonary disease. Prospective comparative studies of ALV versus other currently used manually selected modes of mechanical ventilation, such as the one reported in this article, should confirm the safety and identify the benefits of this form of advanced closed-loop mechanical ventilation technology.

  19. Mechanisms of lung aging.

    PubMed

    Brandenberger, Christina; Mühlfeld, Christian

    2017-03-01

    Lung aging is associated with structural remodeling, a decline of respiratory function and a higher susceptibility to acute and chronic lung diseases. Individual factors that modulate pulmonary aging include basic genetic configuration, environmental exposure, life-style and biography of systemic diseases. However, the actual aging of the lung takes place in pulmonary resident cells and is closely linked to aging of the immune system (immunosenescence). Therefore, this article reviews the current knowledge about the impact of aging on pulmonary cells and the immune system, without analyzing those factors that may accelerate the aging process in depth. Hallmarks of aging include alterations at molecular, cellular and cell-cell interaction levels. Because of the great variety of cell types in the lung, the consequences of aging display a broad spectrum of phenotypes. For example, aging is associated with more collagen and less elastin production by fibroblasts, thus increasing pulmonary stiffness and lowering compliance. Decreased sympathetic airway innervation may increase the constriction status of airway smooth muscle cells. Aging of resident and systemic immune cells leads to a pro-inflammatory milieu and reduced capacity of fighting infectious diseases. The current review provides an overview of cellular changes occurring with advancing age in general and in several cell types of the lung as well as of the immune system. Thereby, this survey not only aims at providing a better understanding of the mechanisms of pulmonary aging but also to identify gaps in knowledge that warrant further investigations.

  20. How Are Lung Carcinoid Tumors Staged?

    MedlinePlus

    ... Tumor Early Detection, Diagnosis, and Staging How Are Lung Carcinoid Tumors Staged? The stage of a cancer ... Your Doctor About Lung Carcinoid Tumors? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  1. How Are Lung Carcinoid Tumors Diagnosed?

    MedlinePlus

    ... Tumor Early Detection, Diagnosis, and Staging How Are Lung Carcinoid Tumors Diagnosed? Certain signs and symptoms might ... Your Doctor About Lung Carcinoid Tumors? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  2. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  3. Lung pair phantom

    DOEpatents

    Olsen, Peter C.; Gordon, N. Ross; Simmons, Kevin L.

    1993-01-01

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an "authentic lung tissue" or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  4. Lung pair phantom

    DOEpatents

    Olsen, P.C.; Gordon, N.R.; Simmons, K.L.

    1993-11-30

    The present invention is a material and method of making the material that exhibits improved radiation attenuation simulation of real lungs, i.e., an ``authentic lung tissue`` or ALT phantom. Specifically, the ALT phantom is a two-part polyurethane medium density foam mixed with calcium carbonate, potassium carbonate if needed for K-40 background, lanthanum nitrate, acetone, and a nitrate or chloride form of a radionuclide. This formulation is found to closely match chemical composition and linear attenuation of real lungs. The ALT phantom material is made according to established procedures but without adding foaming agents or preparing thixotropic concentrate and with a modification for ensuring uniformity of density of the ALT phantom that is necessary for accurate simulation. The modification is that the polyurethane chemicals are mixed at a low temperature prior to pouring the polyurethane mixture into the mold.

  5. [Indium lung disease].

    PubMed

    Nakano, Makiko; Omae, Kazuyuki

    2014-02-01

    "Indium lung" is a new occupational lung disease. The global demand for indium, the major material used in manufacturing flat-screen display panels, has skyrocketed since the 1990s (Japan comprises 85% of the worldwide demand). The first case was reported in Japan in 2003, followed by seven cases (interstitial pneumonia and emphysema) in Japan. Two pulmonary alveolar proteinosis (PAP) cases in the USA followed in 2011. Indium lung has been described as interstitial pneumonia, pneumothorax, emphysema, and PAP. In 2013, The Japan Ministry of Health, Labor and Welfare issued an "Ordinance on the Prevention of Hazards Due to Specified Chemical Substances" requiring employers to provide regular health checks for employees and measurements of work environment concentrations of respirable indium dust.

  6. Lung mass, right upper lung - chest x-ray (image)

    MedlinePlus

    This picture is a chest x-ray of a person with a lung mass. This is a front view, where the lungs are the two dark areas and ... visible in the middle of the chest. The x-ray shows a mass in the right upper lung, ...

  7. Particles causing lung disease.

    PubMed Central

    Kilburn, K H

    1984-01-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response, appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. The insidious and probably most important human lung disease due to particles is bronchiolar obstruction and obliteration, producing progressive impairment of air flow. The responsible particle is the complex combination of poorly digestive lipids and complex carbohydrates with active chemicals which we call cigarette smoke. More research is needed to perfect, correct and

  8. Lung-MAP Clinical Trial

    Cancer.gov

    A collection of material about the Lung-MAP study, which will examine treatment outcomes for patients with squamous cell lung cancer assigned to different targeted drugs based on the results of genomic tumor profiling.

  9. Seniors' Lungs Can Tackle Exercise

    MedlinePlus

    ... news/fullstory_167082.html Seniors' Lungs Can Tackle Exercise Researchers find older adults' respiratory systems keep up ... News) If seniors want to start a vigorous exercise program, there's a good chance their lungs can ...

  10. Lung Cancer Rates by State

    MedlinePlus

    ... HPV-Associated Ovarian Prostate Skin Uterine Cancer Home Lung Cancer Rates by State Language: English Español (Spanish) ... incidence data are currently available. Rates of Getting Lung Cancer by State The number of people who ...

  11. National Lung Screening Trial (NLST)

    Cancer.gov

    The National Lung Screening Trial (NLST), a research study sponsored by the National Cancer Institute that used low-dose helical CT scans or chest X-ray to screen men and women at risk for lung cancer.

  12. The ALCHEMIST Lung Cancer Trial

    Cancer.gov

    A collection of material about the ALCHEMIST lung cancer trial that will examine tumor tissue from patients with early-stage, completely resected lung cancer for gene mutations in the EGFR and ALK genes, and a

  13. What Are Lung Function Tests?

    MedlinePlus

    ... COPD How the Lungs Work Idiopathic Pulmonary Fibrosis Sarcoidosis Send a link to NHLBI to someone by ... the Lungs Work Idiopathic Pulmonary Fibrosis Oxygen Therapy Sarcoidosis Stress Testing Rate This Content: Updated: December 9, ...

  14. Small Cell Lung Cancer

    PubMed Central

    Kalemkerian, Gregory P.; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura QM; Downey, Robert J.; Gandhi, Leena; Ganti, Apar Kishor P.; Govindan, Ramaswamy; Grecula, John C.; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W.; Merritt, Robert E.; Moran, Cesar A.; Niell, Harvey B.; O’Malley, Janis; Patel, Jyoti D.; Ready, Neal; Rudin, Charles M.; Williams, Charles C.; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted. PMID:23307984

  15. Small cell lung cancer.

    PubMed

    Kalemkerian, Gregory P; Akerley, Wallace; Bogner, Paul; Borghaei, Hossein; Chow, Laura Qm; Downey, Robert J; Gandhi, Leena; Ganti, Apar Kishor P; Govindan, Ramaswamy; Grecula, John C; Hayman, James; Heist, Rebecca Suk; Horn, Leora; Jahan, Thierry; Koczywas, Marianna; Loo, Billy W; Merritt, Robert E; Moran, Cesar A; Niell, Harvey B; O'Malley, Janis; Patel, Jyoti D; Ready, Neal; Rudin, Charles M; Williams, Charles C; Gregory, Kristina; Hughes, Miranda

    2013-01-01

    Neuroendocrine tumors account for approximately 20% of lung cancers; most (≈15%) are small cell lung cancer (SCLC). These NCCN Clinical Practice Guidelines in Oncology for SCLC focus on extensive-stage SCLC because it occurs more frequently than limited-stage disease. SCLC is highly sensitive to initial therapy; however, most patients eventually die of recurrent disease. In patients with extensive-stage disease, chemotherapy alone can palliate symptoms and prolong survival in most patients; however, long-term survival is rare. Most cases of SCLC are attributable to cigarette smoking; therefore, smoking cessation should be strongly promoted.

  16. Radiotherapy for lung cancer

    SciTech Connect

    Bleehen, N.M.; Cox, J.D.

    1985-05-01

    The role of radiation therapy in the management of lung cancer was reviewed at a workshop held in Cambridge, England, in June 1984. It was concluded that there was a continuing role for radiation therapy in the primary management of small cell lung cancer, including the loco-regional treatment for patients with limited disease. Radical radiotherapy for patients with non-small cell carcinoma could be curative for a proportion of patients with limited disease. Careful planning and quality control was essential. Palliative radiotherapy provided useful treatment for many other patients. Other related aspects of treatment are also presented.

  17. Poverty and lung health.

    PubMed

    Rusen, I D; Squire, S Bertel; Billo, Nils E

    2010-04-01

    The International Union Against Tuberculosis and Lung Disease (The Union) held its 40th World Conference on Lung Health in Cancun, Mexico, between 3 and 7 December 2009. It was attended by over 2000 delegates from 104 countries around the world. The conference featured four stimulating plenary sessions and an extensive selection of scientific symposia. A total of 1125 abstracts were also presented from five broad categories: clinical trials and TB basic science, clinical research for treatment and care, epidemiology, education, advocacy and social issues, and policy and program implementation. In addition, the conference was preceded by a series of well-attended postgraduate courses and workshops.

  18. Lung Ablation: Whats New?

    PubMed

    Xiong, Lillian; Dupuy, Damian E

    2016-07-01

    Lung cancer had an estimated incidence of 221,200 in 2015, making up 13% of all cancer diagnoses. Tumor ablation is an important treatment option for nonsurgical lung cancer and pulmonary metastatic patients. Radiofrequency ablation has been used for over a decade with newer modalities, microwave ablation, cryoablation, and irreversible electroporation presenting as additional and possibly improved treatment options for patients. This minimally invasive therapy is best for small primary lesions or favorably located metastatic tumors. These technologies can offer palliation and sometimes cure of thoracic malignancies. This article discusses the current available technologies and techniques available for tumor ablation.

  19. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease.

    PubMed

    Warburton, Dorothy; Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-Yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-Ha; Wigler, Michael; Levy, Dan

    2014-01-01

    Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.

  20. The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

    PubMed Central

    Ronemus, Michael; Kline, Jennie; Jobanputra, Vaidehi; Williams, Ismee; Anyane-Yeboa, Kwame; Chung, Wendy; Yu, Lan; Wong, Nancy; Awad, Danielle; Yu, Chih-yu; Leotta, Anthony; Kendall, Jude; Yamrom, Boris; Lee, Yoon-ha; Wigler, Michael; Levy, Dan

    2013-01-01

    Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable pheno-types and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo. PMID:23979609

  1. Lung Mechanics in Marine Mammals

    DTIC Science & Technology

    2012-09-30

    lung mechanics in vivo during spontaneous breathing (dynamic) and mechanical ventilation (static), and the static compliance of the excised lung after...to depth. Physiological Zoology, 1982. 55(1): p. 105-111. 6. Fahlman, A., et al., Estimating the effect of lung collapse and pulmonary shunt on gas...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Lung Mechanics in Marine Mammals Andreas Fahlman

  2. Environmental radiation and the lung

    PubMed Central

    Hamrick, Philip E.; Walsh, Phillip J.

    1974-01-01

    Environmental sources of radioactive materials and their relation to lung doses and lung burdens are described. The approaches used and the problems encountered in estimating lung doses are illustrated. Exposure to radon daughter products is contrasted to exposure to plutonium as particular examples of the hazards associated with radioactive materials of different chemical and physical characteristics. PMID:4620334

  3. [Lung auscultation--an overview].

    PubMed

    Bürgi, Urs; Huber, Lars Christian

    2015-07-01

    The auscultation of the lungs is - among anamnesis - the most important part in the assessment of patients presenting with pulmonary symptoms. The lung auscultation is reproducible, cost efficient and very helpful to distinguish between differential diagnoses, in particular in emergency situations. Detection and description of lung sounds requires experience and should be performed by strict adherence to the internationally accepted terminology.

  4. Particles causing lung disease

    SciTech Connect

    Kilburn, K.H.

    1984-04-01

    The lung has a limited number of patterns of reaction to inhaled particles. The disease observed depends upon the location: conducting airways, terminal bronchioles and alveoli, and upon the nature of inflammation induced: acute, subacute or chronic. Many different agents cause narrowing of conducting airways (asthma) and some of these cause permanent distortion or obliteration of airways as well. Terminal bronchioles appear to be particularly susceptible to particles which cause goblet cell metaplasia, mucous plugging and ultimately peribronchiolar fibrosis. Cancer is the last outcome at the bronchial level and appears to depend upon continuous exposure to or retention of an agent in the airway and failure of the affected cells to be exfoliated which may be due to squamous metaplasia. Alveoli are populated by endothelial cells, Type I or pavement epithelial cells and metabolically active cuboidal Type II cells that produce the lungs specific surfactant, dipalmytol lecithin. Disturbances of surfactant lead to edema in distal lung while laryngeal edema due to anaphylaxis or fumes may produce asphyxia. Physical retention of indigestible particles or retention by immune memory responses may provoke hyaline membranes, stimulate alveolar lipoproteinosis and finally fibrosis. This later exuberant deposition of connective tissue has been best studied in the occupational pneumoconioses especially silicosis and asbestosis. In contrast emphysema a catabolic response appears frequently to result from leakage or release of lysosomal proteases into the lung during processing of cigarette smoke particles. 164 references, 1 figure, 2 tables.

  5. Lung Cancer Brain Metastases.

    PubMed

    Goldberg, Sarah B; Contessa, Joseph N; Omay, Sacit B; Chiang, Veronica

    2015-01-01

    Brain metastases are common among patients with lung cancer and have been associated with significant morbidity and limited survival. However, the treatment of brain metastases has evolved as the field has advanced in terms of central nervous system imaging, surgical technique, and radiotherapy technology. This has allowed patients to receive improved treatment with less toxicity and more durable benefit. In addition, there have been significant advances in systemic therapy for lung cancer in recent years, and several treatments including chemotherapy, targeted therapy, and immunotherapy exhibit activity in the central nervous system. Utilizing systemic therapy for treating brain metastases can avoid or delay local therapy and often allows patients to receive effective treatment for both intracranial and extracranial disease. Determining the appropriate treatment for patients with lung cancer brain metastases therefore requires a clear understanding of intracranial disease burden, tumor histology, molecular characteristics, and overall cancer prognosis. This review provides updates on the current state of surgery and radiotherapy for the treatment of brain metastases, as well as an overview of systemic therapy options that may be effective in select patients with intracranial metastases from lung cancer.

  6. Lung transplant - slideshow

    MedlinePlus

    ... anatomy URL of this page: //medlineplus.gov/ency/presentations/100120.htm Lung transplant - series—Normal anatomy To use the sharing features on this page, please enable JavaScript. Go to slide 1 out of 5 Go to slide 2 ...

  7. Stereology of the lung.

    PubMed

    Schneider, Jan Philipp; Ochs, Matthias

    2013-01-01

    Many scientific projects require a quantitative assessment of organ, tissue and cell (ultra)structure. Such quantitative (morphometric) data are essential to make statistically valid comparisons between experimental groups. The structures of interest are measured at different microscopic levels. However, measurements in microscopy pose two problems: 1) Only a small fraction of the whole biological system can be analyzed (sampling problem). 2) The analysis is performed on nearly two-dimensional (physical, optical or virtual) sections through the object although the aim is to obtain biologically meaningful three-dimensional data (3D vs 2D problem). These problems are solved by the application of unbiased sampling and measurement tools known as stereology. This chapter gives a brief introduction to the theory and practical application of stereology, using the lung as an example. Stereological tools needed to quantify volume, number and surface area are introduced and examples are given how to estimate total lung volume, volume of lung parenchyma, alveolar surface area and number of alveolar epithelial type II cells per lung.

  8. An amyloid lung

    PubMed Central

    Zundel, W. E.; Prior, A. P.

    1971-01-01

    A 55-year-old housewife died from an illness characterized by progressive respiratory incapacity. Changes were confined to the lungs and consisted of a diffuse infiltration by amyloid. No adequate cause was found for this amyloid, and we suggest that this is a case of primary alveolar septal amyloidosis. Images PMID:5559913

  9. Agenesis of the lung.

    PubMed

    Sbokos, C G; McMillan, I K

    1977-07-01

    Agenesis of the lung is rare. The cases of ten patients with this malformation are recorded and illustrated. Most had congenital malformation of other organs, especially the heart, as well. All had hypoplasia of the pulmonary artery or its branches. A pantaloon-like appearance of the trachea and the main bronchi on the bronchograms is described. Exercise tolerance was impaired in all patients.

  10. Chemoprevention of Lung Cancer

    PubMed Central

    Szabo, Eva; Mao, Jenny T.; Lam, Stephen; Reid, Mary E.

    2013-01-01

    Background: Lung cancer is the most common cause of cancer death in men and women in the United States. Cigarette smoking is the main risk factor. Former smokers are at a substantially increased risk of developing lung cancer compared with lifetime never smokers. Chemoprevention refers to the use of specific agents to reverse, suppress, or prevent the process of carcinogenesis. This article reviews the major agents that have been studied for chemoprevention. Methods: Articles of primary, secondary, and tertiary prevention trials were reviewed and summarized to obtain recommendations. Results: None of the phase 3 trials with the agents β-carotene, retinol, 13-cis-retinoic acid, α-tocopherol, N-acetylcysteine, acetylsalicylic acid, or selenium has demonstrated beneficial and reproducible results. To facilitate the evaluation of promising agents and to lessen the need for a large sample size, extensive time commitment, and expense, surrogate end point biomarker trials are being conducted to assist in identifying the most promising agents for later-stage chemoprevention trials. With the understanding of important cellular signaling pathways and the expansion of potentially important targets, agents (many of which target inflammation and the arachidonic acid pathway) are being developed and tested which may prevent or reverse lung carcinogenesis. Conclusions: By integrating biologic knowledge, additional early-phase trials can be performed in a reasonable time frame. The future of lung cancer chemoprevention should entail the evaluation of single agents or combinations that target various pathways while working toward identification and validation of intermediate end points. PMID:23649449

  11. Automated lung segmentation in digital chest tomosynthesis

    PubMed Central

    Wang, Jiahui; Dobbins, James T.; Li, Qiang

    2012-01-01

    Purpose: The purpose of this study was to develop an automated lung segmentation method for computerized detection of lung nodules in digital chest tomosynthesis. Methods: The authors collected 45 digital tomosynthesis scans and manually segmented reference lung regions in each scan to assess the performance of the method. The authors automated the technique by calculating the edge gradient in an original image for enhancing lung outline and transforming the edge gradient image to polar coordinate space. The authors then employed a dynamic programming technique to delineate outlines of the unobscured lungs in the transformed edge gradient image. The lung outlines were converted back to the original image to provide the final segmentation result. The above lung segmentation algorithm was first applied to the central reconstructed tomosynthesis slice because of the absence of ribs overlapping lung structures. The segmented lung in the central slice was then used to guide lung segmentation in noncentral slices. The authors evaluated the segmentation method by using (1) an overlap rate of lung regions, (2) a mean absolute distance (MAD) of lung borders, (3) a Hausdorff distance of lung borders between the automatically segmented lungs and manually segmented reference lungs, and (4) the fraction of nodules included in the automatically segmented lungs. Results: The segmentation method achieved mean overlap rates of 85.7%, 88.3%, and 87.0% for left lungs, right lungs, and entire lungs, respectively; mean MAD of 4.8, 3.9, and 4.4 mm for left lungs, right lungs, and entire lungs, respectively; and mean Hausdorrf distance of 25.0 mm, 25.5 mm, and 30.1 mm for left lungs, right lungs, and entire lungs, respectively. All of the nodules inside the reference lungs were correctly included in the segmented lungs obtained with the lung segmentation method. Conclusions: The method achieved relatively high accuracy for lung segmentation and will be useful for computer-aided detection

  12. Visual anatomical lung CT scan assessment of lung recruitability.

    PubMed

    Chiumello, Davide; Marino, Antonella; Brioni, Matteo; Menga, Federica; Cigada, Irene; Lazzerini, Marco; Andrisani, Maria C; Biondetti, Pietro; Cesana, Bruno; Gattinoni, Luciano

    2013-01-01

    The computation of lung recruitability in acute respiratory distress syndrome (ARDS) is advocated to set positive end-expiratory pressure (PEEP) for preventing lung collapse. The quantitative lung CT scan, obtained by manual image processing, is the reference method but it is time consuming. The aim of this study was to evaluate the accuracy of a visual anatomical analysis compared with a quantitative lung CT scan analysis in assessing lung recruitability. Fifty sets of two complete lung CT scans of ALI/ARDS patients computing lung recruitment were analyzed. Lung recruitability computed at an airway pressure of 5 and 45 cm H(2)O was defined as the percentage decrease in the collapsed/consolidated lung parenchyma assessed by two expert radiologists using a visual anatomical analysis and as the decrease in not aerated lung regions using a quantitative analysis computed by dedicated software. Lung recruitability was 11.3 % (interquartile range 7.39-16.41) and 15.5 % (interquartile range 8.18-21.43) with the visual anatomical and quantitative analysis, respectively. In the Bland-Altman analysis, the bias and agreement bands between the visual anatomical and quantitative analysis were -2.9 % (-11.8 to +5.9 %). The ROC curve showed that the optimal cutoff values for the visual anatomical analysis in predicting high versus low lung recruitability was 8.9 % (area under the ROC curve 0.9248, 95 % CI 0.8550-0.9946). Considering this cutoff, the sensitivity, specificity, and diagnostic accuracy were 0.96, 0.76, and 0.86, respectively. Visual anatomical analysis can classify patients into those with high and low lung recruitability allowing more intensivists to get access to lung recruitability assessment.

  13. Lung Volumes and Emphysema in Smokers with Interstitial Lung Abnormalities

    PubMed Central

    Washko, George R.; Hunninghake, Gary M.; Fernandez, Isis E.; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C.; Estépar, Raúl San José; Lynch, David A.; Brehm, John M.; Andriole, Katherine P.; Diaz, Alejandro A.; Khorasani, Ramin; D’Aco, Katherine; Sciurba, Frank C.; Silverman, Edwin K.; Hatabu, Hiroto; Rosas, Ivan O.

    2011-01-01

    BACKGROUND Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. METHODS We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. RESULTS Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (−0.444 liters; 95% confidence interval [CI], −0.596 to −0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of −950 Hounsfield units (−3%; 95% CI, −4 to −2; P<0.001) and −910 Hounsfield units (−10%; 95% CI, −12 to −8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. CONCLUSIONS In smokers, interstitial lung abnormalities — which were present on about 1 of every 12 HRCT scans — were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the

  14. Lung cancer in Brazil.

    PubMed

    Algranti, E; Menezes, A M; Achutti, A C

    2001-04-01

    Lung cancer is the second leading cause of death in Brazil, after exclusion of external causes. Registries in the country are not reliable because of under-registration and limited coverage. Incidence rates for Brazil are less then half those for selected areas with good registries. Crude and adjusted incidence and mortality rates for lung cancer are rising, particularly among women. The main reason is the acceleration in tobacco consumption and the spread of smoking among women. At present, approximately 40% of men and 25% of women, 15 years of age or older, are current smokers. In the state of Rio Grande do Sul, where registries are reliable, incidence and mortality for males are similar to US data and the figures for women are rapidly approaching those for men. Occupations associated with risks of exposure to respiratory carcinogens show a rise in the incidence of lung cancer in the industrialized area of São Paulo. The main occupational risk in Brazil is exposure to mineral dusts, silica, or asbestos. Although about 15 million Brazilians are exposed to pesticides, agricultural workers were not a risk group for lung cancer in a case-control study. Pesticides containing arsenic and dichlorodiphenyltrichloroethane (DDT) are banned. In recent years, a trend towards a decrease in male smoking has been noted, but there is still a high tobacco exposure burden in both males and females, with a forecast of a further increase in rates of lung cancer incidence and deaths. Control of respiratory carcinogens at work continues to be a problem, particularly in the present scenario of economic and political pressures on Brazil and other developing nations. Semin Oncol 28:143-152. Copyright 2001 by W.B. Saunders Company.

  15. Organ allocation in lung transplant.

    PubMed

    Davis, Steven Q; Garrity, Edward R

    2007-11-01

    Since the first successful single-lung transplant in 1983 and double-lung transplant in 1986, thousands of patients have benefited from the procedures. Until 1995, allocation of donor lungs was based purely on time on the waiting list. In 1995, a 90-day credit was given to patients with idiopathic pulmonary fibrosis, while still maintaining allocation based on waiting list time. In 2005, the lung allocation score (LAS) was implemented, dramatically changing the way lungs are allocated. This article will explore the reasons for the creation of the LAS, the design of the score, early experience with transplant results under the new system, and further changes that may be made to the system of lung allocation. As surgical techniques and medical management evolve, so to will the management of potential donors and the allocation of their organs, with the aim of benefiting patients needing lung transplantation in the United States.

  16. Lung carcinogenesis by tobacco smoke.

    PubMed

    Hecht, Stephen S

    2012-12-15

    Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This article discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers' lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year. Copyright © 2012 UICC.

  17. Lung Carcinogenesis by Tobacco Smoke

    PubMed Central

    Hecht, Stephen S.

    2012-01-01

    Cigarette smoke is a complex mixture of chemicals including multiple genotoxic lung carcinogens. The classic mechanisms of carcinogen metabolic activation to DNA adducts, leading to miscoding and mutations in critical growth control genes, applies to this mixture but some aspects are difficult to establish because of the complexity of the exposure. This paper discusses certain features of this mechanism including the role of nicotine and its receptors; lung carcinogens, co-carcinogens and related substances in cigarette smoke; structurally characterized DNA adducts in the lungs of smokers; the mutational consequences of DNA adduct formation in smokers’ lungs; and biomarkers of nicotine and carcinogen uptake as related to lung cancer. While there are still uncertainties which may never be fully resolved, the general mechanisms by which cigarette smoking causes lung cancer are well understood and provide insights relevant to prevention of lung cancer, the number one cancer killer in the world, causing 1.37 million deaths per year. PMID:22945513

  18. Technetium-fibrinogen lung scanning in canine lung contusion

    SciTech Connect

    Geller, E.; Khaw, B.A.; Strauss, H.W.; Carvalho, A.C.; Rajagopalan, B.; Jones, R.; Zapol, W.M.

    1984-07-01

    To detect experimentally induced acute lung contusion in anesthetized dogs, serial radionuclide images of the lung were recorded following intravenous infusion of 99mTc-labelled human fibrinogen (Tc-HF). The accumulation of Tc-HF in canine lungs was serially quantitated for up to 20 hours after lung contusion. A contusion (number1) was produced in one lung, Tc-HF was injected IV after 15 minutes, and 75 minutes later a contralateral lung contusion (number2) was produced in a series of 14 dogs. At autopsy the excised lungs were scanned, sectioned, and counted for radioactivity. Radiolabelled fibrinogen accumulated within 2-4 minutes of contusion number2 and remained stable over the next 20 hours in 14 dogs; contusion number1 was barely visible in four dogs. Lung Tc-HF activity in the central region of contusion number2 remained sixfold higher than in normal lung tissue. These data suggest that following lung contusion, fibrinogen deposition occurs rapidly and remains stable over a 20-hour interval of observation.

  19. Respiratory Viral Infections in Chronic Lung Diseases.

    PubMed

    Britto, Clemente J; Brady, Virginia; Lee, Seiwon; Dela Cruz, Charles S

    2017-03-01

    Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis (CF) and interstitial lung diseases (ILD), affect many individuals worldwide. Patients with these chronic lung diseases are susceptible to respiratory lung infections and some of these viral infections can contribute to disease pathogenesis. This review highlights the associations of lung infections and the respective chronic lung diseases and how infection in the different lung diseases affects disease exacerbation and progression. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Regeneration of the lung: Lung stem cells and the development of lung mimicking devices.

    PubMed

    Schilders, Kim A A; Eenjes, Evelien; van Riet, Sander; Poot, André A; Stamatialis, Dimitrios; Truckenmüller, Roman; Hiemstra, Pieter S; Rottier, Robbert J

    2016-04-23

    Inspired by the increasing burden of lung associated diseases in society and an growing demand to accommodate patients, great efforts by the scientific community produce an increasing stream of data that are focused on delineating the basic principles of lung development and growth, as well as understanding the biomechanical properties to build artificial lung devices. In addition, the continuing efforts to better define the disease origin, progression and pathology by basic scientists and clinicians contributes to insights in the basic principles of lung biology. However, the use of different model systems, experimental approaches and readout systems may generate somewhat conflicting or contradictory results. In an effort to summarize the latest developments in the lung epithelial stem cell biology, we provide an overview of the current status of the field. We first describe the different stem cells, or progenitor cells, residing in the homeostatic lung. Next, we focus on the plasticity of the different cell types upon several injury-induced activation or repair models, and highlight the regenerative capacity of lung cells. Lastly, we summarize the generation of lung mimics, such as air-liquid interface cultures, organoids and lung on a chip, that are required to test emerging hypotheses. Moreover, the increasing collaboration between distinct specializations will contribute to the eventual development of an artificial lung device capable of assisting reduced lung function and capacity in human patients.

  1. Lung Cancer Biomarkers.

    PubMed

    Villalobos, Pamela; Wistuba, Ignacio I

    2017-02-01

    The molecular characterization of lung cancer has changed the classification and treatment of these tumors, becoming an essential component of pathologic diagnosis and oncologic therapy decisions. Through the recognition of novel biomarkers, such as epidermal growth factor receptor mutations and anaplastic lymphoma kinase translocations, it is possible to identify subsets of patients who benefit from targeted molecular therapies. The success of targeted anticancer therapies and new immunotherapy approaches has created a new paradigm of personalized therapy and has led to accelerated development of new drugs for lung cancer treatment. This article focuses on clinically relevant cancer biomarkers as targets for therapy and potential new targets for drug development. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. [Epidemiology of lung cancer].

    PubMed

    Becker, N

    2010-08-01

    Lung cancer is by far the most common form of cancer worldwide and in Germany is now "only" still the commonest cause of death from cancer. The most important single risk factor is smoking but in selected population groups, for example in the professional area, other factors can also play a role which cannot be ignored and open up a corresponding potential for prevention. Effective early detection procedures are at present unknown. The most promising, however, is multislice computed tomography (MSCT) which for this reason is presently being tested for effectiveness in several large research projects. The results are not expected for some years. Until then the early detection of lung cancer with MSCT cannot be considered suitable for routine use but can only be justified within the framework of research studies.

  3. Immunotherapy in Lung Cancer.

    PubMed

    Du, Lingling; Herbst, Roy S; Morgensztern, Daniel

    2017-02-01

    The treatment of patients with good performance status and advanced stage non-small cell lung cancer has been based on the use of first-line platinum-based doublet and second-line docetaxel. Immunotherapy represents a new therapeutic approach with the potential for prolonged benefit. Although the vaccines studied have not shown benefit in patients with non-small cell lung cancer, immune checkpoint inhibitors against the PD-1/PD-L1 axis showed increased overall survival compared with docetaxel in randomized clinical trials, which led to the approval of nivolumab and pembrolizumab. Because only a minority of patients benefit from this class of drugs, there has been an intense search for biomarkers.

  4. Fire-eater's lung.

    PubMed

    Załęska, Jolanta; Błaszczyk, Arkadiusz; Jakubowska, Lilia; Szopiński, Janusz; Polaczek, Mateusz; Grudny, Jacek; Zych, Jacek; Roszkowski-Śliż, Kazimierz

    2016-01-01

    Fire eater's lung (FEL) is an acute hydrocarbon pneumonitis caused by aspiration or inhalation into airways of liquid hydrocarbons. This disorder is classified into distinct form of chemical toxic pneumonitis. An amateur fire-eater is presented in this work. He accidentally aspirated into airways about 1/3 of glass of grill lighter fluid composed of mixture of liquid hydrocarbons. A few hours after this incident he had severe symptoms like weakness, high temperature, midsternal pleuritic chest pain, myalgia of the back, shortness of breath, and dry cough. Radiologic examination revealed consolidations with well-defined cavitary lesions (pneumatoceles) in lower lobes mainly in the left lower lobe. After one week of this event clinical improvement was observed. The lesions resolved nearly completly during three months. The review of the literature connected with fire-eater's lung is also presented.

  5. Nutrition aspects of lung cancer.

    PubMed

    Cranganu, Andreea; Camporeale, Jayne

    2009-12-01

    Lung cancer is the most common type of cancer, excluding nonmelanoma skin cancer, and is the leading cause of cancer death in the United States. Notable carcinogens involved in the development of lung cancer include smoking, secondhand smoke, and radon. Lung cancer is divided into 2 major types: non-small-cell lung cancer, the most prevalent, and small-cell lung cancer. Treatment includes surgery, chemotherapy, radiation, or a combination of the same. Medical nutrition therapy is often required for nutrition-related side effects of cancer treatment, which include but are not limited to anorexia, nausea and vomiting, and esophagitis. The best protection against lung cancer is avoidance of airborne carcinogens and increased consumption of fruits and vegetables. Studies have shown that smokers taking large amounts of beta-carotene and vitamin A supplements had increased lung cancer incidence and mortality. However, ingestion of beta-carotene from foods, along with a diet rich in fruits and vegetables, has a protective role against lung disease. The use of complementary and alternative medicine by lung cancer patients is prevalent; therefore, clinicians should investigate whether complementary and alternative therapies are used by patients and advise them on the use of these therapies to avoid any potential side effects and interactions with conventional therapies. The article concludes with a case study of a patient with non-small-cell lung cancer and illustrates the use of medical nutrition therapy in relation to cancer treatment side effects.

  6. Hyperoxic Acute Lung Injury

    PubMed Central

    Kallet, Richard H; Matthay, Michael A

    2013-01-01

    Prolonged breathing of very high FIO2 (FIO2 ≥ 0.9) uniformly causes severe hyperoxic acute lung injury (HALI) and, without a reduction of FIO2, is usually fatal. The severity of HALI is directly proportional to PO2 (particularly above 450 mm Hg, or an FIO2 of 0.6) and exposure duration. Hyperoxia produces extraordinary amounts of reactive O2 species that overwhelms natural antioxidant defenses and destroys cellular structures through several pathways. Genetic predisposition has been shown to play an important role in HALI among animals, and some genetics-based epidemiologic research suggests that this may be true for humans as well. Clinically, the risk of HALI likely occurs when FIO2exceeds 0.7, and may become problematic when FIO2 exceeds 0.8 for an extended period of time. Both high-stretch mechanical ventilation and hyperoxia potentiate lung injury and may promote pulmonary infection. During the 1960s, confusion regarding the incidence and relevance of HALI largely reflected such issues as the primitive control of FIO2, the absence of PEEP, and the fact that at the time both ALI and ventilator-induced lung injury were unknown. The advent of PEEP and precise control over FIO2, as well as lung-protective ventilation, and other adjunctive therapies for severe hypoxemia, has greatly reduced the risk of HALI for the vast majority of patients requiring mechanical ventilation in the 21st century. However, a subset of patients with very severe ARDS requiring hyperoxic therapy is at substantial risk for developing HALI, therefore justifying the use of such adjunctive therapies. PMID:23271823

  7. [Secondary lung cancers].

    PubMed

    Etienne-Mastroïanni, Bénédicte; Freyer, Gilles; Cordier, Jean-François

    2003-04-01

    Lung is the most common site of metastatic involvement for many malignant tumors. The most frequent abnormalities are solitary or multiple pulmonary nodules (large "cannonball" nodules or diffuse miliary pattern), and lymphangitic carcinomatosis. Pulmonary metastases usually occur in a context of a previously known tumour, but sometimes may reveal a latent tumour. Most patients receive palliative treatment with chemotherapy, or hormone therapy (for metastases of breast cancer, thyroid, endometrial carcinoma or prostatic cancer). Patients may rarely benefit from resection of pulmonary metastases.

  8. Angiosarcoma of the lung

    PubMed Central

    Grafino, Mónica; Alves, Paula; de Almeida, Margarida Mendes; Garrido, Patrícia; Hasmucrai, Direndra; Teixeira, Encarnação; Sotto-Mayor, Renato

    2016-01-01

    Angiosarcoma is a rare malignant vascular tumor. Pulmonary involvement is usually attributable to metastasis from other primary sites, primary pulmonary angiosarcoma therefore being quite uncommon. We report a case of angiosarcoma with pulmonary involvement, probably primary to the lung, which had gone untreated for more than two years. We describe this rare neoplasm and its growth, as well as the extensive local invasion and hematogenous metastasis at presentation. We also discuss its poor prognosis. PMID:26982044

  9. Marijuana and lung diseases.

    PubMed

    Joshi, Manish; Joshi, Anita; Bartter, Thaddeus

    2014-03-01

    Cannabis sativa (marijuana) is used throughout the world, and its use is increasing. In much of the world, marijuana is illicit. While inhalation of smoke generated by igniting dried components of the plant is the most common way marijuana is used, there is concern over potential adverse lung effects. The purpose of this review is to highlight recent studies that explore the impact upon the respiratory system of inhaling marijuana smoke. Smoking marijuana is associated with chronic bronchitis symptoms and large airway inflammation. Occasional use of marijuana with low cumulative use is not a risk factor for the development of chronic obstructive pulmonary disease. The heavy use of marijuana alone may lead to airflow obstruction. The immuno-histopathologic and epidemiologic evidence in marijuana users suggests biological plausibility of marijuana smoking as a risk for the development of lung cancer; at present, it has been difficult to conclusively link marijuana smoking and cancer development. There is unequivocal evidence that habitual or regular marijuana smoking is not harmless. A caution against regular heavy marijuana usage is prudent. The medicinal use of marijuana is likely not harmful to lungs in low cumulative doses, but the dose limit needs to be defined. Recreational use is not the same as medicinal use and should be discouraged.

  10. Regional tidal lung strain in mechanically ventilated normal lungs.

    PubMed

    Paula, Luis Felipe; Wellman, Tyler J; Winkler, Tilo; Spieth, Peter M; Güldner, Andreas; Venegas, Jose G; Gama de Abreu, Marcelo; Carvalho, Alysson R; Vidal Melo, Marcos F

    2016-12-01

    Parenchymal strain is a key determinant of lung injury produced by mechanical ventilation. However, imaging estimates of volumetric tidal strain (ε = regional tidal volume/reference volume) present substantial conceptual differences in reference volume computation and consideration of tidally recruited lung. We compared current and new methods to estimate tidal volumetric strains with computed tomography, and quantified the effect of tidal volume (VT) and positive end-expiratory pressure (PEEP) on strain estimates. Eight supine pigs were ventilated with VT = 6 and 12 ml/kg and PEEP = 0, 6, and 12 cmH2O. End-expiratory and end-inspiratory scans were analyzed in eight regions of interest along the ventral-dorsal axis. Regional reference volumes were computed at end-expiration (with/without correction of regional VT for intratidal recruitment) and at resting lung volume (PEEP = 0) corrected for intratidal and PEEP-derived recruitment. All strain estimates demonstrated vertical heterogeneity with the largest tidal strains in middependent regions (P < 0.01). Maximal strains for distinct estimates occurred at different lung regions and were differently affected by VT-PEEP conditions. Values consistent with lung injury and inflammation were reached regionally, even when global measurements were below critical levels. Strains increased with VT and were larger in middependent than in nondependent lung regions. PEEP reduced tidal-strain estimates referenced to end-expiratory lung volumes, although it did not affect strains referenced to resting lung volume. These estimates of tidal strains in normal lungs point to middependent lung regions as those at risk for ventilator-induced lung injury. The different conditions and topography at which maximal strain estimates occur allow for testing the importance of each estimate for lung injury.

  11. Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

    PubMed Central

    Shinchi, Yusuke; Sanada, Mune; Motooka, Yamato; Fujino, Kosuke; Mori, Takeshi; Suzuki, Makoto

    2016-01-01

    Background The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA. Methods The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed. Results The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03). Conclusion The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas. PMID:27526096

  12. Morphometric examination of native lungs in human lung allograft recipients.

    PubMed

    Wiebe, B M; Burton, C M; Milman, N; Iversen, M; Andersen, C B

    2006-11-01

    The aim of the study was to estimate the degree of lung damage in patients with alpha(1)-antitrypsin (alpha1AT) deficiency, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) at the time of lung transplantation. Using unbiased stereological methods, lung-, bronchial- and vessel-volume, capillary length, and alveolar surface area and densities were estimated in recipient lungs from 21 consecutive patients with pre-transplant diagnoses including COPD (n=7), alpha1AT deficiency (n=6) and CF (n=8). Six unused adult donor lungs served as controls. Information relating to patient demography and pre-transplant lung function was obtained by retrospective chart review. Disease groups differed significantly with respect to demographics and pre-transplant lung function. Total lung volume was similar in all groups. Bronchial volume was significantly larger in CF patients compared to the control group (p<0.0001) and to the other two diagnostic groups: alpha1AT deficiency (p=0.0001) and COPD (p<0.0001). Alveolar surface density and capillary length density were significantly lower in patients with alpha1AT deficiency and COPD compared to controls (p<0.0001, respectively) and to patients with CF (p<0.0002, respectively). There were no correlations between clinical lung function and morphometric measurements. We conclude that unbiased microscopic stereological morphometry is an evolving science with the potential to elucidate pulmonary disease pathogenesis.

  13. Cholinergic Targets in Lung Cancer.

    PubMed

    Spindel, Eliot R

    2016-01-01

    Lung cancers express an autocrine cholinergic loop in which secreted acetylcholine can stimulate tumor growth through both nicotinic and muscarinic receptors. Because activation of mAChR and nAChR stimulates growth; tumor growth can be stimulated by both locally synthesized acetylcholine as well as acetylcholine from distal sources and from nicotine in the high percentage of lung cancer patients who are smokers. The stimulation of lung cancer growth by cholinergic agonists offers many potential new targets for lung cancer therapy. Cholinergic signaling can be targeted at the level of choline transport; acetylcholine synthesis, secretion and degradation; and nicotinic and muscarinic receptors. In addition, the newly describe family of ly-6 allosteric modulators of nicotinic signaling such as lynx1 and lynx2 offers yet another new approach to novel lung cancer therapeutics. Each of these targets has their potential advantages and disadvantages for the development of new lung cancer therapies which are discussed in this review.

  14. [Asbestos-related lung cancer].

    PubMed

    Lotti, M

    2010-01-01

    Lung cancer is the leading cause of tumour death and a large percentage of it is associated with tobacco smoking. Epidemiology has shown that asbestos cumulative exposures increase the risk of lung cancer to a variable extent, depending on the manufacturing process and the specific job. The risk appears relatively small (< or = 2) and is detectable after massive exposures only. Clinical diagnosis of asbestos-related lung cancer is based upon medical history (exposures > 25 ff.ml years double the risk), possible lung fibrosis and counts of asbestos bodies and fibers in bronchoalveolar lavage and lung tissues. Pleural plaques do not correlate with the cumulative exposures that are associated with lung cancer. The multiplicative interaction between smoke and asbestos is only detectable when the risk associated with asbestos exposure is increased, i.e. after high exposures.

  15. The microbiome and the lung.

    PubMed

    Cui, Lijia; Morris, Alison; Huang, Laurence; Beck, James M; Twigg, Homer L; von Mutius, Erika; Ghedin, Elodie

    2014-08-01

    Investigation of the human microbiome has become an important field of research facilitated by advances in sequencing technologies. The lung, which is one of the latest body sites being explored for the characterization of human-associated microbial communities, has a microbiome that is suspected to play a substantial role in health and disease. In this review, we provide an overview of the basics of microbiome studies. Challenges in the study of the lung microbiome are highlighted, and further attention is called to the optimization and standardization of methodologies to explore the role of the lung microbiome in health and disease. We also provide examples of lung microbial communities associated with disease or infection status and discuss the role of fungal species in the lung. Finally, we review studies demonstrating that the environmental microbiome can influence lung health and disease, such as the finding that the diversity of microbial exposure correlates inversely with the development of childhood asthma.

  16. Retrospective Analysis of Lung Transplant Recipients Found to Have Unexpected Lung Cancer in Explanted Lungs.

    PubMed

    Nakajima, Takahiro; Cypel, Marcelo; de Perrot, Marc; Pierre, Andrew; Waddell, Tom; Singer, Lianne; Roberts, Heidi; Keshavjee, Shaf; Yasufuku, Kazuhiro

    2015-01-01

    Unexpected lung cancer is sometimes found in explanted lungs. The objective of this study was to review these patients and their outcomes to better understand and optimize management protocols for lung transplant candidates with pulmonary nodules. Retrospective analysis of pretransplant imaging and clinicopathologic characteristics of patients who were found to have lung cancer in their explanted lungs was performed. From January 2003 to December 2012, 13 of 853 lung transplant recipients were found to have unexpected lung cancer in their explanted lung (1.52%). Of them, 9 cases were for interstitial lung disease (2.8%; 9/321 recipients) and 4 cases were for chronic obstructive pulmonary disease (1.57%; 4/255 recipients). The median period between computed tomographic scan and lung transplantation was 2.40 months (range: 0.5-19.2). On computed tomographic scan, only 3 cases were shown to possibly have a neoplasm by the radiologist. The staging of these lung cancers was as follows: 3 cases of IA, 1 case of IB, 5 cases of IIA, 1 case of IIIA, and 3 cases of IV. Of 13 cases, 9 died owing to cancer progression. On the contrary, only 1 stage I case with small cell lung cancer showed cancer recurrence. The median survival time was 339 days, and the 3-year survival rate was 11.0%. In conclusion, most of the patients with unexpected lung cancer showed poor prognosis except for the early-stage disease. The establishment of proper protocol for management of such nodules is important to improve the management of candidates who are found to have pulmonary nodules on imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Lung Mechanics in Marine Mammals

    DTIC Science & Technology

    2014-09-30

    volume expressed as a percent of estimated total lung capacity [ TLC = 0.135 x Mb^0.92, 11, 12] for 3 individual California sea lions (Zalophus...airway pressure minus esophageal pressure) and inspired volume expressed as a percent of estimated total lung capacity [ TLC = 0.135 x Mb^0.92, 11, 12...esophageal pressure) and inspired volume expressed as a percent of estimated total lung capacity [ TLC = 0.135 x Mb^0.92, 11, 12] for an excised lung and live

  18. Pulmonary Rehabilitation in Lung Cancer.

    PubMed

    Wang, Hongmei; Liu, Xin; Rice, Shawn J; Belani, Chandra P

    2016-10-01

    Lung cancer remains a challenging disease with high morbidity and mortality despite targeted therapy. Symptom burden related to cancer impairs quality of life and functional status in patients with lung cancer and in survivors. Pulmonary rehabilitation has been recognized as an effective, noninvasive intervention for patients with chronic respiratory disease. It is well established that pulmonary rehabilitation benefits patients with chronic obstruction pulmonary disease through improved exercise capacity and symptoms. Evidence is increasing that the benefit of pulmonary rehabilitation can be applied to patients with lung cancer. Comprehensive pulmonary rehabilitation has made its way as a cornerstone of integrated care for patients with lung cancer.

  19. Current status of lung transplantation.

    PubMed

    Lau, C L; Patterson, G A

    2003-11-01

    Two decades have passed since the first successful clinical lung transplant was performed in 1983, and, in the interim, lung transplantation has become the preferred treatment option for a variety of end-stage pulmonary diseases. Remarkable progress has been made in the field through refinement of technique and improved understanding of transplant immunology and microbiology. Unfortunately, donor shortages continue to limit the more widespread application of lung transplantation. In order to address this issue, marginal donors, living lobar and split lung donor techniques, and nonheartbeating donors have been used clinically to increase the number of donor lungs available. Chronic rejection of the lung allograft is currently the major hurdle limiting longterm survival. To date, prevention of known risk factors and treatment strategies have not lessened the devastating toll this process has on lung transplant survival. Better understanding of the cause of chronic rejection is needed in order to develop novel strategies for its treatment. Promotion of immune tolerance is a promising area that could potentially eliminate chronic rejection. The present article discusses recent advances in lung transplantation. It also details the major issues facing the field today. Only through continued clinical and experimental investigation will lung transplantation eventually reach its full potential.

  20. [Radiotherapy for primary lung carcinoma].

    PubMed

    Giraud, P; Lacornerie, T; Mornex, F

    2016-09-01

    Indication, doses, technique of radiotherapy and concomitant chemotherapy, for primary lung carcinoma are presented. The recommendations for delineation of the target volumes and organs at risk are detailed.

  1. Brain injury requires lung protection

    PubMed Central

    Lopez-Aguilar, Josefina

    2015-01-01

    The paper entitled “The high-mobility group protein B1-Receptor for advanced glycation endproducts (HMGB1-RAGE) axis mediates traumatic brain injury (TBI)-induced pulmonary dysfunction in lung transplantation” published recently in Science Translational Medicine links lung failure after transplantation with alterations in the axis HMGB1-RAGE after TBI, opening a new field for exploring indicators for the early detection of patients at risk of developing acute lung injury (ALI). The lung is one of the organs most vulnerable to the inflammatory cascade triggered by TBI. HMGB1 is an alarm in that can be released from activated immune cells in response to tissue injury. Increased systemic HMGB1 concentration correlates with poor lung function before and after lung transplant, confirming its role in acute ALI after TBI. HMGB1 exerts its influence by interacting with several receptors, including the RAGE receptor. RAGE also plays an important role in the onset of innate immune inflammatory responses, and systemic levels of RAGE are strongly associated with ALI and clinical outcomes in ventilator-induced lung injury. RAGE ligation to HMGB1 triggers the amplification of the inflammatory cascade involving nuclear factor-κB (NF-κB) activation. Identifying early biomarkers that mediate pulmonary dysfunction will improve outcomes not only in lung transplantation, but also in other scenarios. These novel findings show that upregulation of the HMGB1-RAGE axis plays an important role in brain-lung crosstalk. PMID:26046092

  2. Assessment of Peripheral Lung Mechanics

    PubMed Central

    Bates, Jason H.T.; Suki, Béla

    2008-01-01

    The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies. PMID:18463006

  3. Assessment of peripheral lung mechanics.

    PubMed

    Bates, Jason H T; Suki, Béla

    2008-11-30

    The mechanical properties of the lung periphery are major determinants of overall lung function, and can change dramatically in disease. In this review we examine the various experimental techniques that have provided data pertaining to the mechanical properties of the lung periphery, together with the mathematical models that have been used to interpret these data. These models seek to make a clear distinction between the central and peripheral compartments of the lung by encapsulating functional differences between the conducing airways, the terminal airways and the parenchyma. Such a distinction becomes problematic in disease, however, because of the inevitable onset of regional variations in mechanical behavior throughout the lung. Accordingly, lung models are used both in the inverse sense as vehicles for extracting physiological insight from experimental data, and in the forward sense as virtual laboratories for the testing of specific hypothesis about mechanisms such as the effects of regional heterogeneities. Pathologies such as asthma, acute lung injury and emphysema can alter the mechanical properties of the lung periphery through the direct alteration of intrinsic tissue mechanics, the development of regional heterogeneities in mechanical function, and the complete derecruitment of airspaces due to airway closure and alveolar collapse. We are now beginning to decipher the relative contributions of these various factors to pathological alterations in peripheral lung mechanics, which may eventually lead to the development and assessment of novel therapies.

  4. Facts about Hypoplastic Left Heart Syndrome

    MedlinePlus

    ... left and right sides of the heart: the patent ductus arteriosus and the patent foramen ovale . Normally, these openings will close a ... functioning left side of the heart through the patent ductus arteriosus and the patent foramen ovale. The ...

  5. Lung and renal transplantation.

    PubMed

    Caetano Mota, Patrícia; Vaz, Ana Paula; Castro Ferreira, Inês; Bustorff, Manuela; Damas, Carla

    2009-01-01

    Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. To evaluate patients admitted to the Renal Transplant Unit (RTU) of Hospital de S. João with respiratory disease. We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Thirty-six patients were included. Mean age 55.2 (+/-13.4) years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9%) or tacrolimus (22.2%) or rapamycin (13.9%). Thirty-one patients (86.1%) presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2%) pneumonias, 5 (16.1%) opportunistic infections, 2 (6.5%) tracheobronchitis, and 1 case (3.2%) of lung abscesses. Microbiological agent was identified in 7 cases (22.6%). Five patients (13.9%) presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%), diagnostic in 10 cases (66.7%). Mean hospital stay was 17.1 (+/-18.5) days and no related death was observed. Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

  6. Rheumatoid Arthritis: Can It Affect the Lungs?

    MedlinePlus

    Rheumatoid arthritis: Can it affect the lungs? Can rheumatoid arthritis affect your lungs? Answers from April Chang-Miller, M.D. Although rheumatoid arthritis primarily affects joints, it sometimes causes lung disease ...

  7. Potential targets for lung squamous cell carcinoma

    Cancer.gov

    Researchers have identified potential therapeutic targets in lung squamous cell carcinoma, the second most common form of lung cancer. The Cancer Genome Atlas (TCGA) Research Network study comprehensively characterized the lung squamous cell carcinoma gen

  8. Stages of Small Cell Lung Cancer

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  9. Treatment Option Overview (Small Cell Lung Cancer)

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  10. General Information about Small Cell Lung Cancer

    MedlinePlus

    ... Cancer Prevention Lung Cancer Screening Research Small Cell Lung Cancer Treatment (PDQ®)–Patient Version General Information About Small Cell Lung Cancer Go to Health Professional Version Key Points ...

  11. Lung Cancer and Interstitial Lung Diseases: A Systematic Review

    PubMed Central

    Archontogeorgis, Kostas; Steiropoulos, Paschalis; Tzouvelekis, Argyris; Nena, Evangelia; Bouros, Demosthenes

    2012-01-01

    Interstitial lung diseases (ILDs) represent a heterogeneous group of more than two hundred diseases of either known or unknown etiology with different pathogenesis and prognosis. Lung cancer, which is the major cause of cancer death in the developed countries, is mainly attributed to cigarette smoking and exposure to inhaled carcinogens. Different studies suggest a link between ILDs and lung cancer, through different pathogenetic mechanisms, such as inflammation, coagulation, dysregulated apoptosis, focal hypoxia, activation, and accumulation of myofibroblasts as well as extracellular matrix accumulation. This paper reviews current evidence on the association between lung cancer and interstitial lung diseases such as idiopathic pulmonary fibrosis, sarcoidosis, systemic sclerosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic lupus erythematosus, and pneumoconiosis. PMID:22900168

  12. Second lung cancers in patients successfully treated for lung cancer.

    PubMed

    Johnson, B E; Cortazar, P; Chute, J P

    1997-08-01

    The rate of developing second lung cancers and other aerodigestive tumors in patients who have been treated for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is approximately 10-fold higher than other adult smokers. The risk of second lung cancers in patients surviving resection of NSCLC is approximately 1% to 2% per year. The series reported show that the patients who develop second NSCLCs tend to have early-stage NSCLC (predominantly stage I and II). The survival of patients after the second resection of lung cancer is similar to that of patients presenting with initial NSCLC. The risk of second lung cancers in patients surviving SCLC is 2% to 14% per patient per year and increases two- to seven-fold with the passage of time from 2 to 10 years. The risk of second lung cancers in patients treated for SCLC appears to be higher than that found in patients with NSCLC who were treated only with surgical resection. In addition, the chances of successful resection of second primary NSCLCs in patients who were treated for SCLC is much less than that for patients with metachronous lung cancers after an initial NSCLC. Patients treated for SCLC who continue to smoke cigarettes increase their rate of developing second lung cancers. The contribution of chest radiation and chemotherapy administration to the risk of developing second lung tumors remain to be defined but may be responsible for some of the increased risk in patients treated for SCLC compared to patients undergoing a surgical resection for NSCLC.

  13. Your Lungs and Respiratory System

    MedlinePlus

    ... air is necessary for keeping humans (and many animals) alive. And the two parts that are large and in charge when it comes to breathing? If you guessed your lungs, you're right! Your lungs make up one of the largest ...

  14. Metastatic cancer to the lung

    MedlinePlus

    ... lungs may include: Fluid between the lung and chest wall (pleural effusion), which can cause shortness of breath or pain when taking a deep breath Further spread of the cancer Side effects of chemotherapy or radiation therapy When to Contact a Medical Professional Call ...

  15. Asbestos-related lung disease

    SciTech Connect

    Westerfield, B.T. )

    1992-06-01

    Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers.22 references.

  16. Mitochondria in lung disease.

    PubMed

    Cloonan, Suzanne M; Choi, Augustine M K

    2016-03-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell's most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets.

  17. Polonium and Lung Cancer

    PubMed Central

    Zagà, Vincenzo; Lygidakis, Charilaos; Chaouachi, Kamal; Gattavecchia, Enrico

    2011-01-01

    The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties. PMID:21772848

  18. Mitochondria in lung disease

    PubMed Central

    Cloonan, Suzanne M.; Choi, Augustine M.K.

    2016-01-01

    Mitochondria are a distinguishing feature of eukaryotic cells. Best known for their critical function in energy production via oxidative phosphorylation (OXPHOS), mitochondria are essential for nutrient and oxygen sensing and for the regulation of critical cellular processes, including cell death and inflammation. Such diverse functional roles for organelles that were once thought to be simple may be attributed to their distinct heteroplasmic genome, exclusive maternal lineage of inheritance, and ability to generate signals to communicate with other cellular organelles. Mitochondria are now thought of as one of the cell’s most sophisticated and dynamic responsive sensing systems. Specific signatures of mitochondrial dysfunction that are associated with disease pathogenesis and/or progression are becoming increasingly important. In particular, the centrality of mitochondria in the pathological processes and clinical phenotypes associated with a range of lung diseases is emerging. Understanding the molecular mechanisms regulating the mitochondrial processes of lung cells will help to better define phenotypes and clinical manifestations associated with respiratory disease and to identify potential diagnostic and therapeutic targets. PMID:26928034

  19. Nanoparticle delivery in infant lungs

    PubMed Central

    Semmler-Behnke, Manuela; Kreyling, Wolfgang G.; Schulz, Holger; Takenaka, Shinji; Butler, James P.; Henry, Frank S.; Tsuda, Akira

    2012-01-01

    The lung surface is an ideal pathway to the bloodstream for nanoparticle-based drug delivery. Thus far, research has focused on the lungs of adults, and little is known about nanoparticle behavior in the immature lungs of infants. Here, using nonlinear dynamical systems analysis and in vivo experimentation in developing animals, we show that nanoparticle deposition in postnatally developing lungs peaks at the end of bulk alveolation. This finding suggests a unique paradigm, consistent with the emerging theory that as alveoli form through secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in, significantly enhancing particle deposition. This finding has significant implications for the application of nanoparticle-based inhalation therapeutics in young children with immature lungs from birth to ˜2 y of age. PMID:22411799

  20. Anesthetic management for lung transplantation.

    PubMed

    Castillo, Maria

    2011-02-01

    For end-stage lung disease refractory to medical management, lung transplantation remains the definitive treatment. However, this procedure presents unique challenges for the anesthesiologist. This review summarizes the recent literature regarding this procedure and its anesthetic management. Changes in the lung allocation system have had an impact on the characteristics of patients presenting for lung transplantation, resulting in patients who are older, sicker, and possibly presenting for retransplantation. In addition, various donor and recipient characteristics, including BMI, race, sex, and comorbidities such as diabetes and atrial fibrillation, have been shown to influence outcomes. Perioperative management, particularly colloid administration, adequate pain control, and treatment of pulmonary hypertension, may also affect outcomes. Careful preoperative assessment of pulmonary and cardiac function and comorbidities are particularly important for this patient population. Lung protective strategies, intra-operative transesophageal echocardiogram, pulmonary artery catheterization, cardiopulmonary bypass, inhaled nitric oxide, and inhaled prostacyclin are all important tools for the anesthesiologist to optimize patient care.

  1. Biomarkers in acute lung injury.

    PubMed

    Mokra, Daniela; Kosutova, Petra

    2015-04-01

    Acute respiratory distress syndrome (ARDS) and its milder form acute lung injury (ALI) may result from various diseases and situations including sepsis, pneumonia, trauma, acute pancreatitis, aspiration of gastric contents, near-drowning etc. ALI/ARDS is characterized by diffuse alveolar injury, lung edema formation, neutrophil-derived inflammation, and surfactant dysfunction. Clinically, ALI/ARDS is manifested by decreased lung compliance, severe hypoxemia, and bilateral pulmonary infiltrates. Severity and further characteristics of ALI/ARDS may be detected by biomarkers in the plasma and bronchoalveolar lavage fluid (or tracheal aspirate) of patients. Changed concentrations of individual markers may suggest injury or activation of the specific types of lung cells-epithelial or endothelial cells, neutrophils, macrophages, etc.), and thereby help in diagnostics and in evaluation of the patient's clinical status and the treatment efficacy. This chapter reviews various biomarkers of acute lung injury and evaluates their usefulness in diagnostics and prognostication of ALI/ARDS.

  2. Gastroesophageal reflux and lung disease.

    PubMed

    Meyer, Keith C

    2015-08-01

    Gastroesophageal reflux (GER) can cause respiratory symptoms and may trigger, drive and/or worsen airway disorders, interstitial lung diseases and lung allograft dysfunction. Whether lifestyle changes and acid suppression alone can counter and prevent the adverse effects of GER on the respiratory tract remains unclear. Recent data suggest that antireflux surgery may be more effective in preventing lung disease progression in patients with idiopathic pulmonary fibrosis or lung transplant recipients who have evidence of allograft dysfunction associated with the presence of excessive GER. Additional research and clinical trials are needed to determine the role of GER in various lung disorders and identify which interventions are most efficacious in preventing the respiratory consequences of gastroesophageal reflux disease. In addition, measuring biomarkers that indicate that gastric refluxate has been aspirated into the lower respiratory tract (e.g., pepsin and bile acid concentrations in bronchoalveolar lavage fluid) may prove helpful in both diagnosis and therapeutic decision making.

  3. Accuracy and feasibility of dynamic contrast-enhanced 3D MR imaging in the assessment of lung perfusion: comparison with Tc-99 MAA perfusion scintigraphy.

    PubMed

    Yilmaz, E; Akkoclu, A; Degirmenci, B; Cooper, R A; Sengun, B; Gulcu, A; Osma, E; Ucan, E S

    2005-08-01

    The aim of this study was to correlate findings of perfusion magnetic resonance imaging (MRI) and perfusion scintigraphy in cases where there was a suspicion of abnormal pulmonary vasculature, and to evaluate the usefulness of MRI in the detection of perfusion deficits of the lung. In all, 17 patients with suspected abnormality of the pulmonary vasculature underwent dynamic contrast-enhanced MRI. T1-weighted 3D fast-field echo pulse sequences were obtained (TR/TE 3.3/1.58 ms; flip angle 30 degrees; slice thickness 12 to 15 mm). The dynamic study was acquired in the coronal plane following administration of 0.1 mmol/kg gadopentetate dimeglumine. A total of 8 to 10 sections repeated 20 to 25 times at intervals of 1s were performed. Perfusion lung scintigraphy was carried out a maximum of 48 h before the MR examination in all cases. Two radiologists, who were blinded to the clinical data and results of other imaging methods, reviewed all coronal sections. MR perfusion images were independently assessed in terms of segmental or lobar perfusion defects in the 85 lobes of the 17 individuals, and the findings were compared with the results of scintigraphy. Of the 17 patients, 8 were found to have pulmonary emboli, 2 chronic obstructive pulmonary disease with emphysema, 2 bullous emphysema, 2 Takayasu arteritis and 1 had a hypoplastic pulmonary artery. Pulmonary perfusion was completely normal in 2 cases. In 35 lobes, perfusion defects were detected using both methods, in 4 with MR alone and in 9 only with scintigraphy. There was good agreement between MRI and scintigraphy findings (kappa=0.695). Pulmonary perfusion MRI is a new alternative to scintigraphy in the evaluation of pulmonary perfusion for various lung disorders. In addition, this technique allows measurement and quantification of pulmonary perfusion abnormalities.

  4. Reversal of dependent lung collapse predicts response to lung recruitment in children with early acute lung injury.

    PubMed

    Wolf, Gerhard K; Gómez-Laberge, Camille; Kheir, John N; Zurakowski, David; Walsh, Brian K; Adler, Andy; Arnold, John H

    2012-09-01

    To describe the resolution of regional atelectasis and the development of regional lung overdistension during a lung-recruitment protocol in children with acute lung injury. Prospective interventional trial. Pediatric intensive care unit. Ten children with early (<72 hrs) acute lung injury. Sustained inflation maneuver (positive airway pressure of 40 cm H2O for 40 secs), followed by a stepwise recruitment maneuver (escalating plateau pressures by 5 cm H2O every 15 mins) until physiologic lung recruitment, defined by PaO2 + PaCO2 ≥400 mm Hg, was achieved. Regional lung volumes and mechanics were measured using electrical impedance tomography. Patients that responded to the stepwise lung-recruitment maneuver had atelectasis in 54% of the dependent lung regions, while nonresponders had atelectasis in 10% of the dependent lung regions (p = .032). In the pressure step preceding physiologic lung recruitment, a significant reversal of atelectasis occurred in 17% of the dependent lung regions (p = .016). Stepwise recruitment overdistended 8% of the dependent lung regions in responders, but 58% of the same regions in nonresponders (p < .001). Lung compliance in dependent lung regions increased in responders, while compliance in nonresponders did not improve. In contrast to the stepwise recruitment maneuver, the sustained inflation did not produce significant changes in atelectasis or oxygenation: atelectasis was only reversed in 12% of the lung (p = .122), and there was only a modest improvement in oxygenation (27 ± 14 mm Hg, p = .088). Reversal of atelectasis in the most dependent lung region preceded improvements in gas exchange during a stepwise lung-recruitment strategy. Lung recruitment of dependent lung areas was accompanied by considerable overdistension of nondependent lung regions. Larger amounts of atelectasis in dependent lung areas were associated with a positive response to a stepwise lung-recruitment maneuver.

  5. What's New in Lung Carcinoid Tumor Research and Treatment?

    MedlinePlus

    ... Tumor About Lung Carcinoid Tumors What’s New in Lung Carcinoid Tumor Research and Treatment? Many medical centers ... Lung Carcinoid Tumor Research and Treatment? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  6. LUNG CANCER AND PULMONARY THROMBOEMBOLISM

    PubMed Central

    Cukic, Vesna; Ustamujic, Aida

    2015-01-01

    Introduction: Malignant diseases including lung cancer are the risk for development of pulmonary thromboembolism (PTE). Objective: To show the number of PTE in patients with lung cancer treated in Clinic for pulmonary diseases and TB “Podhrastovi” in three-year period: from 2012-2014. Material and methods: This is the retrospective study in which we present the number of various types of lung cancer treated in three-year period, number and per cent of PTE in different types of lung carcinoma, number and per cent of PTE of all diagnosed PTE in lung carcinoma according to the type of carcinoma. Results: In three-year period (from 2012 to 2014) 1609 patients with lung cancer were treated in Clinic for pulmonary diseases and TB “Podhrastovi” Clinical Centre of Sarajevo University. 42 patients: 25 men middle –aged 64.4 years and 17 women middle- aged 66.7 or 2.61% of all patients with lung cancer had diagnosed PTE. That was the 16. 7% of all patients with PTE treated in Clinic “Podhrastovi “in that three-year period. Of all 42 patients with lung cancer and diagnosed PTE 3 patients (7.14%) had planocellular cancer, 4 patients (9.53%) had squamocellular cancer, 9 (21.43%) had adenocarcinoma, 1 (2.38%) had NSCLC, 3 (7.14 %) had microcellular cancer, 1 (2.38%) had neuroendocrine cancer, 2 (4.76%) had large cell-macrocellular and 19 (45.24%) had histological non-differentiated lung carcinoma. Conclusion: Malignant diseases, including lung cancer, are the risk factor for development of PTE. It is important to consider the including anticoagulant prophylaxis in these patients and so to slow down the course of diseases in these patients. PMID:26622205

  7. Advances in lung ultrasound.

    PubMed

    Francisco, Miguel José; Rahal, Antonio; Vieira, Fabio Augusto Cardillo; Silva, Paulo Savoia Dias da; Funari, Marcelo Buarque de Gusmão

    2016-01-01

    Ultrasound examination of the chest has advanced in recent decades. This imaging modality is currently used to diagnose several pathological conditions and provides qualitative and quantitative information. Acoustic barriers represented by the aerated lungs and the bony framework of the chest generate well-described sonographic artifacts that can be used as diagnostic aids. The normal pleural line and A, B, C, E and Z lines (also known as false B lines) are artifacts with specific characteristics. Lung consolidation and pneumothorax sonographic patterns are also well established. Some scanning protocols have been used in patient management. The Blue, FALLS and C.A.U.S.E. protocols are examples of algorithms using artifact combinations to achieve accurate diagnoses. Combined chest ultrasonography and radiography are often sufficient to diagnose and manage lung and chest wall conditions. Chest ultrasonography is a highly valuable diagnostic tool for radiologists, emergency and intensive care physicians. RESUMO O exame ultrassonográfico do tórax avançou nas últimas décadas, sendo utilizado para o diagnóstico de inúmeras condições patológicas, e fornecendo informações qualitativas e quantitativas. Os pulmões aerados e o arcabouço ósseo do tórax representam barreira sonora para o estudo ultrassonográfico, gerando artefatos que, bem conhecidos, são utilizados como ferramentas diagnósticas. Eco pleural normal, linhas A, linhas B, linhas C, linhas E e Z (conhecidas como falsas linhas B) são artefatos com características peculiares. Os padrões de consolidação e de pneumotórax também são bem estabelecidos. Alguns protocolos têm sido utilizados no manuseio dos pacientes: Blue Protocol, Protocolo FALLS e Protocolo C.A.U.S.E são exemplos de três propostas que, por meio da associação entre os artefatos, permitem sugerir diagnósticos precisos. A ultrassonografia de tórax, aliada à radiografia de tórax, muitas vezes é suficiente para o diagn

  8. Cryotherapy in Treating Patients With Lung Cancer That Has Spread to the Other Lung or Parts of the Body

    ClinicalTrials.gov

    2017-01-17

    Advanced Malignant Mesothelioma; Extensive Stage Small Cell Lung Cancer; Lung Metastases; Recurrent Malignant Mesothelioma; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  9. Cannabis and the lung.

    PubMed

    Reid, P T; Macleod, J; Robertson, J R

    2010-12-01

    The use of cannabis is embedded within many societies, mostly used by the young and widely perceived to be safe. Increasing concern regarding the potential for cannabis to cause mental health effects has dominated cannabis research and the potential adverse respiratory effects have received relatively little attention. Studies on cannabis are challenging and subject to confounding by concomitant use of tobacco and other social factors, and while many of the studies referred to in this review are beset by the difficulties inherent in undertaking epidemiological research of the effects of cannabis, there is an emerging concern among many chest physicians who would suggest that habitual smoking of cannabis may contribute to the development of chronic obstructive pulmonary disease, pneumothorax and respiratory infections, including tuberculosis. Special attention should be given to the risk of lung cancer, particularly as biological plausibility may precede epidemiology.

  10. Vanishing lung syndrome

    PubMed Central

    Im, Yunhee; Farooqi, Saad

    2016-01-01

    Giant bullae often mimic pneumothorax on radiographic appearance. We present the case of a 55-year-old man admitted to a referring hospital with dyspnea, cough, and increasing sputum production; he refused thoracotomy for tension pneumothorax and presented to our hospital for a second opinion. A computed tomography (CT) scan at our hospital revealed a giant bulla, which was managed conservatively as an exacerbation of chronic obstructive pulmonary disease. Thoracic surgery was consulted but advised against bullectomy. Giant bullae can easily be misdiagnosed as a pneumothorax, but the management of the two conditions is vastly different. Distinguishing between the two may require CT scan. Symptomatic giant bullae are managed surgically. We highlight the etiology, presentation, diagnosis, and treatment of bullous lung disease, especially in comparison to pneumothorax. PMID:27695175

  11. Lung cancer among Chinese women.

    PubMed

    Gao, Y T; Blot, W J; Zheng, W; Ershow, A G; Hsu, C W; Levin, L I; Zhang, R; Fraumeni, J F

    1987-11-15

    A case-control study involving interviews with 672 female lung cancer patients and 735 population-based controls was conducted to investigate the high rates of lung cancer, notably adenocarcinoma, among women in Shanghai. Cigarette smoking was a strong risk factor, but accounted for only about one-fourth of all newly diagnosed cases of lung cancer. Most patients, particularly with adenocarcinoma, were life-long non-smokers. The risks of lung cancer were higher among women reporting tuberculosis and other pre-existing lung diseases. Hormonal factors were suggested by an increased risk associated with late menopause and by a gradient in the risk of adenocarcinoma with decreasing menstrual cycle length, with a 3-fold excess among women who had shorter cycles. Perhaps most intriguing were associations found between lung cancer and measures of exposure to cooking oil vapors. Risks increased with the numbers of meals cooked by either stir frying, deep frying or boiling; with the frequency of smokiness during cooking; and with the frequency of eye irritation during cooking. Use of rapeseed oil, whose volatiles following high-temperature cooking may be mutagenic, was also reported more often by the cancer patients. The findings thus confirm that factors other than smoking are responsible for the high risk of lung cancer among Chinese women and provide clues for further research, including the assessment of cooking practices.

  12. Radionuclide injury to the lung.

    PubMed Central

    Dagle, G E; Sanders, C L

    1984-01-01

    Radionuclide injury to the lung has been studied in rats, hamsters, dogs, mice and baboons. Exposure of the lung to high dose levels of radionuclides produces a spectrum of progressively more severe functional and morphological changes, ranging from radiation pneumonitis and fibrosis to lung tumors. These changes are somewhat similar for different species. Their severity can be related to the absorbed radiation dose (measured in rads) produced by alpha, beta or gamma radiation emanating from various deposited radionuclides. The chemicophysical forms of radionuclides and spatial-temporal factors are also important variables. As with other forms of injury to the lung, repair attempts are highlighted by fibrosis and proliferation of pulmonary epithelium. Lung tumors are the principal late effect observed in experimental animals following pulmonary deposition of radionuclides at dose levels that do not result in early deaths from radiation pneumonitis or fibrosis. The predominant lung tumors described have been of epithelial origin and have been classified, in decreasing frequency of occurrence, as adenocarcinoma, bronchioloalveolar carcinoma, epidermoid carcinomas and combined epidermoid and adenocarcinoma. Mesothelioma and fibrosarcoma have been observed in rats, but less commonly in other species. Hemangiosarcomas were frequency observed in dogs exposed to beta-gamma emitters, and occasionally in rats exposed to alpha emitters. These morphologic changes in the lungs of experimental animals were reviewed and issues relevant to the prediction of human hazards discussed. PMID:6376095

  13. Lunge performance and its determinants.

    PubMed

    Cronin, John; McNair, Peter J; Marshall, Robert N

    2003-01-01

    For activities such as squash, badminton and fencing, the ability to quickly complete a lunge and return to the start or move off in another direction is critical for success. Determining which strength qualities are important predictors of lunge performance was the focus of this study. Thirty-one male athletes performed: (1) a unilateral maximal squat (one-repetition maximum, 1-RM) and unilateral jump squat (50% 1-RM) on an instrumented supine squat machine, and (2) a forward lunge while attached to a linear transducer. We performed stepwise multiple regression analysis with lunge performance as the dependent variable and various strength, flexibility and anthropometric measures as the independent variables. From the many strength and power measures calculated, time to peak force was the best single predictor of lunge performance, which accounted for 55% of the explained variance. The best three-variable model for predicting lunge performance accounted for 76-85% of the explained variance. The models differed, however, according to whether lunge performance was expressed relative to body mass (time to peak force, mean power and relative strength = 76%) or taken as an absolute value (time to peak force, leg length and flexibility = 85%). We conclude that one to two trials were reliable for strength diagnosis and that one strength measure cannot accurately explain functional performance because other factors, such as body mass, flexibility and leg length, have diverse effects on the statistical models.

  14. The Microbiome of the Lung

    PubMed Central

    Beck, James M.; Young, Vincent B.; Huffnagle, Gary B.

    2012-01-01

    Investigation of the lung microbiome is a relatively new field. Although the lungs were classically believed to be sterile, recently published investigations have identified microbial communities in the lungs of healthy humans. At the present time, there are significant methodologic and technical hurdles that must be addressed in ongoing investigations, including distinguishing the microbiota of the upper and lower respiratory tracts. However, characterization of the lung microbiome is likely to provide important pathogenic insights into cystic fibrosis, respiratory disease of the newborn, chronic obstructive pulmonary disease, and asthma. In addition to characterization of the lung microbiome, the microbiota of the gastrointestinal tract have profound influence on development and maintenance of lung immunity and inflammation. Further study of gastrointestinal-respiratory interactions are likely to yield important insights into the pathogenesis of pulmonary diseases, including asthma. As this field advances over the next several years, we anticipate that studies utilizing larger cohorts, multi-center designs, and longitudinal sampling will add to our knowledge and understanding of the lung microbiome. PMID:22683412

  15. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  16. [Lung cancer and epigenetic modifications].

    PubMed

    Darılmaz Yüce, Gülbahar; Ortaç Ersoy, Ebru

    2016-06-01

    Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA expression, have been reported to play a major role in the genesis of lung cancer. DNA methylation, histone modifications, and RNA expression are epigenetic markers in assesment of early detection, prognosis and evaluation of treatment of lung cancer. In this rewiev we summarize the common epigenetic changes associated with lung cancer to give some clarity to its etiology, and to provide an overview of the potential translational applications of these changes, including applications for early detection, diagnosis, prognostication, and therapeutics.

  17. Tobacco Smoking and Lung Cancer

    PubMed Central

    Furrukh, Muhammad

    2013-01-01

    Tobacco smoking remains the most established cause of lung carcinogenesis and other disease processes. Over the last 50 years, tobacco refinement and the introduction of filters have brought a change in histology, and now adenocarcinoma has become the most prevalent subtype. Over the last decade, smoking also has emerged as a strong prognostic and predictive patient characteristic along with other variables. This article briefly reviews scientific facts about tobacco, and the process and molecular pathways involved in lung carcinogenesis in smokers and never-smokers. The evidence from randomised trials about tobacco smoking’s impact on lung cancer outcomes is also reviewed. PMID:23984018

  18. Occupational and environmental lung disease.

    PubMed

    Seaman, Danielle M; Meyer, Cristopher A; Kanne, Jeffrey P

    2015-06-01

    Occupational and environmental lung disease remains a major cause of respiratory impairment worldwide. Despite regulations, increasing rates of coal worker's pneumoconiosis and progressive massive fibrosis are being reported in the United States. Dust exposures are occurring in new industries, for instance, silica in hydraulic fracking. Nonoccupational environmental lung disease contributes to major respiratory disease, asthma, and COPD. Knowledge of the imaging patterns of occupational and environmental lung disease is critical in diagnosing patients with occult exposures and managing patients with suspected or known exposures. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Pain management in lung cancer.

    PubMed

    Nurwidya, Fariz; Syahruddin, Elisna; Yunus, Faisal

    2016-01-01

    Lung cancer is the leading cause of cancer-related mortality worldwide. Not only burdened by the limited overall survival, lung cancer patient also suffer from various symptoms, such as pain, that implicated in the quality of life. Cancer pain is a complicated and transiently dynamic symptom that results from multiple mechanisms. This review will describe the pathophysiology of cancer pain and general approach in managing a patient with lung cancer pain. The use of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and adjuvant analgesia, as part of the pharmacology therapy along with interventional strategy, will also be discussed.

  20. Types of Childhood Interstitial Lung Disease

    MedlinePlus

    ... from the NHLBI on Twitter. Types of Childhood Interstitial Lung Disease The broad term "childhood interstitial lung disease" (chILD) ... therapeutic intervention Lung and bone marrow transplant-associated lung diseases Diffuse alveolar damage of unknown cause The various types ...

  1. Lung Cancer and Hispanics: Know the Facts

    MedlinePlus

    Lung Cancer and Hispanics: Know the Facts By the National Cancer Institute First, the good news: the number of lung cancer cases diagnosed in ... myth from fact when it comes to lung cancer. So what are the facts?  Smoking is the primary cause of lung cancer. ...

  2. [Current status and future of lung transplantation].

    PubMed

    Date, Hiroshi

    2011-10-01

    Lung transplantation has been a widely accepted treatment modality for patients with end-stage chronic obstructive lung disease (COPD). COPD is the most frequent indication for lung transplantation according to the report from International Society for Lung and Heart Transplantation. However, it is a minor population in Japan. A total of 204 lung transplants have been performed in Japan to date. Among them, 10 patients were suffering from severe COPD. Nine of them received cadaveric lung transplantation and one received living-donor lobar lung transplantation. All are currently alive during follow-up period of 3-87 months.

  3. Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients.

    PubMed

    Wong, Jackson Y; Westall, Glen P; Snell, Gregory I

    2015-12-01

    Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in pediatric patients undergoing lung transplantation (LTx). Whether performed as part of a surveillance protocol or if clinically indicated, fibre-optic bronchoscopy allows direct visualization of the transplanted allograft, and in particular, an assessment of the patency of the bronchial anastomosis (or tracheal anastomosis following heart-lung transplantation). Additionally, bronchoscopy facilitates differentiation of infective processes from rejection episodes through collection and subsequent assessment of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria for the grading of acute cellular rejection is dependent upon the histopathological assessment of biopsy samples collected at the time of bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is generally a safe procedure, although complications related to hemorrhage and pneumothorax are occasionally seen. Airway complications, including stenosis, malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management including balloon dilatation, laser therapy and stent insertion can also be performed bronchoscopically. Finally, bronchoscopy has been and continues to be an important research tool allowing a better understanding of the immuno-biology of the lung allograft through the collection and analysis of collected BAL and TBBx samples. Whilst new investigational tools continue to evolve, the simple visualization and collection of samples within the lung allograft by bronchoscopy remains the gold standard in the evaluation of the lung allograft. This review describes the use and experience of bronchoscopy following lung transplantation in the pediatric setting.

  4. [Current state and development of artificial lungs].

    PubMed

    Mei, Zaoxian; Sun, Xin; Wu, Qi

    2010-12-01

    The artificial lung is a technical device for providing life support; it will be put in use when the natural lungs are failing and are not able to maintain sufficient oxygenation of the body's organ systems. From the viewpoint of long-term development, the artificial lung should be permanently implanted in the body, so that it will substitute for the human pulmonary function partially or completely. In this paper, four artificial lung technologies were expounded with reference to the development and research process of artificial lung. They were extracorporeal membrane oxygenation, intravascular artificial lung, implantable artificial lung, and pumpless extracorporeal lung assist. In this paper were described the structure of the four kinds of artificial lung, the working principle, and their advantages, disadvantages and indications. The prospect of artificial lung was evaluated in the light of the data from the existing animal experiments and from the clinical experience of the centers.

  5. Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model.

    PubMed

    Medeiros, Israel L; Pêgo-Fernandes, Paulo M; Mariani, Alessandro W; Fernandes, Flávio G; Unterpertinger, Fernando V; Canzian, Mauro; Jatene, Fabio B

    2012-09-01

    Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98). The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035). The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816). The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87). The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0), and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71). The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

  6. Single-lung ventilation in pediatric anesthesia.

    PubMed

    Choudhry, Dinesh K

    2005-12-01

    Single-lung ventilation is requested for an increasing spectrum of surgical procedures in infants and children. A clear understanding of the physiology of single-lung ventilation, the techniques of lung separation, and the technical skill necessary to apply these techniques are essential for an anesthesiologist practicing thoracic anesthesia. This article focuses on various devices available for single-lung ventilation in the pediatric age group, the relevant respiratory physiology, and the strategies that optimize oxygenation during one-lung anesthesia.

  7. Radiofrequency Ablation of Lung Tumors

    MedlinePlus

    ... you may need to be admitted overnight for observation. What are Radiofrequency and Microwave Ablation of Lung ... performed on an outpatient basis or with overnight observation in the hospital with general anesthesia. For the ...

  8. Drugs Approved for Lung Cancer

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for lung cancer. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  9. Solubilized xenon 133 lung scintigraphy

    SciTech Connect

    Oates, E.; Sarno, R.C.

    1988-11-01

    Lung scanning using solubilized xenon 133 can provide important information concerning both pulmonary perfusion and ventilation. This technique proved valuable in establishing the diagnosis of congenital lobar emphysema in a 7-month-old baby.

  10. Farmer's lung in Northern Ireland.

    PubMed Central

    Stanford, C F; Hall, G; Chivers, A; Martin, B; Nicholls, D P; Evans, J

    1990-01-01

    A total of 381 farmers in Northern Ireland were studied using a questionnaire, pulmonary function tests, and antibody levels to Micropolyspora faena to assess the incidence of farmer's lung. Twenty (4.9%) had a history of a previous diagnosis of farmer's lung by their doctor. Forty four (10.4%) had delayed onset symptoms compatible with farmer's lung, 32 (7.9%) had precipitant antibody, and 61 (15%) had raised antibody by the enzyme linked immunosorbent (ELISA) method. Restricted lungs were present physiologically in 40 (9.8%). A confirmation of delayed symptoms and precipitant antibody was present in seven (1.7%) whereas delayed symptoms and ELISA antibody was present in nine (2.2%). Using either antibody method only two (0.5%) had a combination of antibody to M faenae, delayed onset symptoms, and restricted pulmonary physiology. PMID:2357452

  11. Farmer's lung in Northern Ireland.

    PubMed

    Stanford, C F; Hall, G; Chivers, A; Martin, B; Nicholls, D P; Evans, J

    1990-05-01

    A total of 381 farmers in Northern Ireland were studied using a questionnaire, pulmonary function tests, and antibody levels to Micropolyspora faena to assess the incidence of farmer's lung. Twenty (4.9%) had a history of a previous diagnosis of farmer's lung by their doctor. Forty four (10.4%) had delayed onset symptoms compatible with farmer's lung, 32 (7.9%) had precipitant antibody, and 61 (15%) had raised antibody by the enzyme linked immunosorbent (ELISA) method. Restricted lungs were present physiologically in 40 (9.8%). A confirmation of delayed symptoms and precipitant antibody was present in seven (1.7%) whereas delayed symptoms and ELISA antibody was present in nine (2.2%). Using either antibody method only two (0.5%) had a combination of antibody to M faenae, delayed onset symptoms, and restricted pulmonary physiology.

  12. Tuberculosis in the lung (image)

    MedlinePlus

    Tuberculosis is caused by a group of organisms: Mycobacterium tuberculosis, M bovis , M africanum and a few other rarer subtypes. Tuberculosis usually appears as a lung (pulmonary) infection. However, ...

  13. Smoking and interstitial lung diseases.

    PubMed

    Margaritopoulos, George A; Vasarmidi, Eirini; Jacob, Joseph; Wells, Athol U; Antoniou, Katerina M

    2015-09-01

    For many years has been well known that smoking could cause lung damage. Chronic obstructive pulmonary disease and lung cancer have been the two most common smoking-related lung diseases. In the recent years, attention has also focused on the role of smoking in the development of interstitial lung diseases (ILDs). Indeed, there are three diseases, namely respiratory bronchiolitis-associated ILD, desquamative interstitial pneumonia and pulmonary Langerhans cell histiocytosis, that are currently considered aetiologically linked to smoking and a few others which are more likely to develop in smokers. Here, we aim to focus on the most recent findings regarding the role of smoking in the pathogenesis and clinical behaviour of ILDs. Copyright ©ERS 2015.

  14. Early detection of lung cancer

    PubMed Central

    Midthun, David E.

    2016-01-01

    Most patients with lung cancer are diagnosed when they present with symptoms, they have advanced stage disease, and curative treatment is no longer an option. An effective screening test has long been desired for early detection with the goal of reducing mortality from lung cancer. Sputum cytology, chest radiography, and computed tomography (CT) scan have been studied as potential screening tests. The National Lung Screening Trial (NLST) demonstrated a 20% reduction in mortality with low-dose CT (LDCT) screening, and guidelines now endorse annual LDCT for those at high risk. Implementation of screening is underway with the desire that the benefits be seen in clinical practice outside of a research study format. Concerns include management of false positives, cost, incidental findings, radiation exposure, and overdiagnosis. Studies continue to evaluate LDCT screening and use of biomarkers in risk assessment and diagnosis in attempt to further improve outcomes for patients with lung cancer. PMID:27158468

  15. Radiation Therapy for Lung Cancer

    MedlinePlus

    ... of the lung cancer and your overall health. Radiation Therapy Radiation is a high-energy X-ray that can ... surgery, chemotherapy or both depending upon the circumstances. Radiation therapy works within cancer cells by damaging their ...

  16. Lung Involvement in Systemic Sclerosis

    PubMed Central

    Hassoun, Paul M.

    2011-01-01

    Summary Scleroderma is a multisystem disease characterized by a severe inflammatory process and exuberant fibrosis. Lung involvement is a frequent complication and a leading cause of morbidity and mortality in this syndrome. Two major pulmonary syndromes are associated with scleroderma; a pulmonary vascular disorder evolving over time into relatively isolated pulmonary arterial hypertension (PAH), and interstitial lung disease (ILD). Each syndrome, when present, is a cause of morbidity and significantly reduces survival of scleroderma patients when compared to patients free of lung complication. When pulmonary hypertension and ILD are combined, survival is further reduced. Current therapy appears to have no meaningful effect on either condition and, thus, there is a need for better understanding of underlying pathogenic mechanisms. This review focuses on clinical, diagnostic, and therapeutic features of PAH and ILD as well as other frequent but less debilitating lung complications of scleroderma. PMID:21195581

  17. Lung embolism with liquid silicone.

    PubMed

    Rodríguez, M A; Martínez, M C; Lopez-Artíguez, M; Soria, M L; Bernier, F; Repetto, M

    1989-03-01

    A lung embolism was reported in a case involving death following repeated injections of liquid silicone for aesthetic reasons. The liquid extracted from the sites of injection was identified as methylsilicone using infrared spectrophotometry, and the presence of silicone in vacuoles in the lung was verified by scanning electron microscopy with energy dispersive X-ray analysis (EDXA). A study has been carried out with rats after intravenous and subcutaneous injections of methylsilicone.

  18. Lung Oxidative Damage by Hypoxia

    PubMed Central

    Araneda, O. F.; Tuesta, M.

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described. PMID:22966417

  19. Lung oxidative damage by hypoxia.

    PubMed

    Araneda, O F; Tuesta, M

    2012-01-01

    One of the most important functions of lungs is to maintain an adequate oxygenation in the organism. This organ can be affected by hypoxia facing both physiological and pathological situations. Exposure to this condition favors the increase of reactive oxygen species from mitochondria, as from NADPH oxidase, xanthine oxidase/reductase, and nitric oxide synthase enzymes, as well as establishing an inflammatory process. In lungs, hypoxia also modifies the levels of antioxidant substances causing pulmonary oxidative damage. Imbalance of redox state in lungs induced by hypoxia has been suggested as a participant in the changes observed in lung function in the hypoxic context, such as hypoxic vasoconstriction and pulmonary edema, in addition to vascular remodeling and chronic pulmonary hypertension. In this work, experimental evidence that shows the implied mechanisms in pulmonary redox state by hypoxia is reviewed. Herein, studies of cultures of different lung cells and complete isolated lung and tests conducted in vivo in the different forms of hypoxia, conducted in both animal models and humans, are described.

  20. Systemic vasculitis and the lung.

    PubMed

    Talarico, Rosaria; Barsotti, Simone; Elefante, Elena; Baldini, Chiara; Tani, Chiara; Mosca, Marta

    2017-01-01

    The purpose of this review is to provide a critical analysis of the recent literature on this topic, with particular focus on the most relevant studies published over the last year. Many studies are published every year on the diagnosis, pathogenesis and treatment of pulmonary involvement in antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). The main subjects covered by this article are the pathogenesis, diagnosis and clinical aspects of lung involvement in ANCA-associated vasculitis and non-ANCA-associated vasculitis. Lung involvement is a common feature in systemic vasculitis. The lungs are one of the most frequently involved organs in systemic vasculitis. In order to provide an update on the recent advances in the pathogenesis, clinical features and novel treatments of lung involvement in systemic vasculitis, a systematic MedLine search has been performed.Most of the data analyzed have confirmed that lung involvement seems to develop more frequently in patients with myeloperoxidase-ANCA-positive AAV, mainly in those with a diagnosis of microscopic polyangiitis (MPA), compared with patients with proteinase 3 ANCA-positive AAV. Moreover, among non-ANCA-associated vasculitis lung involvement may represent a worrying complication of the disease, mainly when associated with vascular involvement.

  1. "Open lung ventilation optimizes pulmonary function during lung surgery".

    PubMed

    Downs, John B; Robinson, Lary A; Steighner, Michael L; Thrush, David; Reich, Richard R; Räsänen, Jukka O

    2014-12-01

    We evaluated an "open lung" ventilation (OV) strategy using low tidal volumes, low respiratory rate, low FiO2, and high continuous positive airway pressure in patients undergoing major lung resections. In this phase I pilot study, twelve consecutive patients were anesthetized using conventional ventilator settings (CV) and then OV strategy during which oxygenation and lung compliance were noted. Subsequently, a lung resection was performed. Data were collected during both modes of ventilation in each patient, with each patient acting as his own control. The postoperative course was monitored for complications. Twelve patients underwent open thoracotomies for seven lobectomies and five segmentectomies. The OV strategy provided consistent one-lung anesthesia and improved static compliance (40 ± 7 versus 25 ± 4 mL/cm H2O, P = 0.002) with airway pressures similar to CV. Postresection oxygenation (SpO2/FiO2) was better during OV (433 ± 11 versus 386 ± 15, P = 0.008). All postoperative chest x-rays were free of atelectasis or infiltrates. No patient required supplemental oxygen at any time postoperatively or on discharge. The mean hospital stay was 4 ± 1 d. There were no complications or mortality. The OV strategy, previously shown to have benefits during mechanical ventilation of patients with respiratory failure, proved safe and effective in lung resection patients. Because postoperative pulmonary complications may be directly attributable to the anesthetic management, adopting an OV strategy that optimizes lung mechanics and gas exchange may help reduce postoperative problems and improve overall surgical results. A randomized trial is planned to ascertain whether this technique will reduce postoperative pulmonary complications. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. [Idiopathic lung fibrosis].

    PubMed

    Leonhardt, L; Geldszus, R; Molitor, S J

    1990-02-01

    In a 39-year-old patient with chronic progressive idiopathic pulmonary fibrosis, the genetic aspects, course and therapeutic possibilities of the disease are discussed. In February, 1987, the English-born patient, Anthony V., attended for initial examination on account of progressive dyspnoea, on which occasion radiology and pulmonary function analysis revealed advanced pulmonary fibrosis. The patient's family history revealed a familial genesis, since both his father (?) and his sister had died of this disease. A comparative of the patient's chest films with original chest films of his sister revealed almost identical findings. Within the previous twelve months, follow-up examinations done on A.V. revealed an increase in the restrictive component (reduction of vital capacity from 2,400 ml to 1,500 ml), development of partial respiratory failure at rest, and global respiratory failure in response to mild ergometric exercise despite intermittent high-dose steroid administrations superimposed on long-term, low-dose steroid therapy. The unfavourable evolution observed over the past 12 months is underscored by an increase in mean pulmonary arterial pressure from 18 mmHg initially to a present 34 mmHg at rest, and 46 mmHg under submaximal ergometric loading. The only option still left to the patient is the possibility of a lung transplantation, which - probably initially unilateral - is scheduled to be carried out in the near future at the Chest Surgery Department of the Medical University at Hannover.

  3. Common lung conditions: environmental pollutants and lung disease.

    PubMed

    Delzell, John E

    2013-06-01

    Exposure to environmental pollutants can have short- and long-term effects on lung health. Sources of air pollution include gases (eg, carbon monoxide, ozone) and particulate matter (eg, soot, dust). In the United States, the Environmental Protection Agency regulates air pollution. Elevated ozone concentrations are associated with increases in lung-related hospitalizations and mortality. Elevated particulate matter pollution increases the risk of cardiopulmonary and lung cancer mortality. Occupations with high exposures to pollutants (eg, heavy construction work, truck driving, auto mechanics) pose higher risk of chronic obstructive lung disease. Some industrial settings (eg, agriculture, sawmills, meat packing plants) also are associated with higher risks from pollutants. The Environmental Protection Agency issues an air quality index for cities and regions in the United States. The upper levels on the index are associated with increases in asthma-related emergency department visits and hospitalizations. Damp and moldy housing might make asthma symptoms worse; individuals from lower socioeconomic groups who live in lower quality housing are particularly at risk. Other household exposures that can have negative effects on lung health include radon, nanoparticles, and biomass fuels.

  4. Multipotent mesenchymal stem cells in lung fibrosis

    PubMed Central

    Khan, Petra; Savic, Spasenija; Tamo, Luca; Lardinois, Didier; Roth, Michael; Tamm, Michael; Geiser, Thomas

    2017-01-01

    Rationale Stem cells have been identified in the human lung; however, their role in lung disease is not clear. We aimed to isolate mesenchymal stem cells (MSC) from human lung tissue and to study their in vitro properties. Methods MSC were cultured from lung tissue obtained from patients with fibrotic lung diseases (n = 17), from emphysema (n = 12), and normal lungs (n = 3). Immunofluorescence stainings were used to characterize MSC. The effect of MSC-conditioned media (MSC-CM) on fibroblast proliferation and on lung epithelial wound repair was studied. Results Expression of CD44, CD90, and CD105 characterized the cells as MSC. Moreover, the cells stained positive for the pluripotency markers Oct3/4 and Nanog. Positive co-stainings of chemokine receptor type 4 (CXCR4) with CD44, CD90 or CD105 indicated the cells are of bone marrow origin. MSC-CM significantly inhibited the proliferation of lung fibroblasts by 29% (p = 0.0001). Lung epithelial repair was markedly increased in the presence of MSC-CM (+ 32%). Significantly more MSC were obtained from fibrotic lungs than from emphysema or control lungs. Conclusions Our study demonstrates enhanced numbers of MSC in fibrotic lung tissue as compared to emphysema and normal lung. The cells inhibit the proliferation of fibroblasts and enhance epithelial repair in vitro. Further in vivo studies are needed to elucidate their potential role in the treatment of lung fibrosis. PMID:28827799

  5. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    PubMed

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  6. Lung cancer and tobacco smoking.

    PubMed

    Boyle, P; Maisonneuve, P

    1995-06-01

    The dominant role of tobacco smoking in the causation of lung cancer has been repeatedly demonstrated over the past 50 years. Current lung cancer rates reflect cigarette smoking habits of men and women in the past decades, but not necessarily current smoking patterns, since there is an interval of several decades between the change in smoking habits in a population and its consequences on lung cancer rates. Over 90% of lung cancer may be avoidable simply through avoidance of cigarette smoking. There is at present a huge premature loss of life world-wide caused by smoking. Rates of lung cancer present in central and eastern Europe at the present time are higher than those ever before recorded elsewhere; lung cancer has increased 10-fold in men and eightfold in women in Japan since 1950. There is a world-wide epidemic of smoking among young women which will be translated into increasing rates of tobacco-related disease, including cancer, in the coming decades. There is another epidemic of lung cancer and tobacco-related deaths building up in China as the cohorts of men in whom tobacco smoking became popular reach ages where cancer is an important hazard. Many solutions have been attempted to reduce cigarette smoking and increasingly many countries are enacting legislation to curb this habit. Cigarette smoking remains the number one target for Public Health action aimed at reducing cancer risk in the general population. General practitioners, hospital physicians and everyone working in oncology have a particularly important exemplary role to play in this process.

  7. Molecular biology of lung cancer.

    PubMed

    Cooper, Wendy A; Lam, David C L; O'Toole, Sandra A; Minna, John D

    2013-10-01

    Lung cancers are characterised by abundant genetic diversity with relatively few recurrent mutations occurring at high frequency. However, the genetic alterations often affect a common group of oncogenic signalling pathways. There have been vast improvements in our understanding of the molecular biology that underpins lung cancer in recent years and this has led to a revolution in the diagnosis and treatment of lung adenocarcinomas (ADC) based on the genotype of an individual's tumour. New technologies are identifying key and potentially targetable genetic aberrations not only in adenocarcinoma but also in squamous cell carcinoma (SCC) of the lung. Lung cancer mutations have been identified in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor (EGFR), BRAF and the parallel phosphatidylinositol 3-kinase (PI3K) pathway oncogenes and more recently in MEK and HER2 while structural rearrangements in ALK, ROS1 and possibly rearranged during transfection (RET) provide new therapeutic targets. Amplification is another mechanism of activation of oncogenes such as MET in adenocarcinoma, fibroblastgrowth factor receptor 1 (FGFR1) and discoidin domain receptor 2 (DDR2) in SCC. Intriguingly, many of these genetic alternations are associated with smoking status and with particular racial and gender differences, which may provide insight into the mechanisms of carcinogenesis and role of host factors in lung cancer development and progression. The role of tumour suppressor genes is increasingly recognised with aberrations reported in TP53, PTEN, RB1, LKB11 and p16/CDKN2A. Identification of biologically significant genetic alterations in lung cancer that lead to activation of oncogenes and inactivation of tumour suppressor genes has the potential to provide further therapeutic opportunities. It is hoped that these discoveries may make a major contribution to improving outcome for patients with this poor prognosis disease.

  8. Acromegalic pneumonomegaly: lung growth in the adult

    PubMed Central

    Brody, Jerome S.; Fisher, Aron B.; Gocmen, Ayhan; DuBois, Arthur B.

    1970-01-01

    Lung size was evaluated with pulmonary function tests in 10 patients with acromegaly, 1 pituitary giant, and 1 patient who had acromegaly but now has hypopituitarism. In the six acromegalic men all lung volumes were increased. The average values and per cent of predicted were total lung capacity 9.1 liters. 139%; functional residual capacity 5.2 liters, 145%; vital capacity 6.0 liters, 134%; and tissue volume 1.1 liters. There was no evidence of airflow obstruction or air trapping. Anatomic dead space was increased in proportion to the large lung volumes. Lung compliance was increased, averaging 0.43 liters/cm H2O, but lung elastic recoil was normal. These studies show that the lung is involved in the general visceromegaly of acromegaly and that lung size increases in acromegalic men as a result of actual lung growth. Despite the large lung volumes, diffusing capacity was normal suggesting that lung growth resulted from an increase in the size rather than from an increase in the number of alveoli. In contrast to the acromegalic men, lung volumes, anatomic dead space and tissue volume were normal in four acromegalic women, suggesting that sex hormones may modify the effect of growth hormone on the lung. Lung size was large in the pituitary giant but lung volumes were normal according to predicted values based on the patient's great height. Lung volumes were normal in the one male who had been acromegalic but who has been hypopituitary for 21 yr. The role of growth hormone in normal postnatal lung growth and in the maintainance of normal lung size remains to be defined. PMID:5422011

  9. Lung Injury After One-Lung Ventilation: A Review of the Pathophysiologic Mechanisms Affecting the Ventilated and the Collapsed Lung.

    PubMed

    Lohser, Jens; Slinger, Peter

    2015-08-01

    Lung injury is the leading cause of death after thoracic surgery. Initially recognized after pneumonectomy, it has since been described after any period of 1-lung ventilation (OLV), even in the absence of lung resection. Overhydration and high tidal volumes were thought to be responsible at various points; however, it is now recognized that the pathophysiology is more complex and multifactorial. All causative mechanisms known to trigger ventilator-induced lung injury have been described in the OLV setting. The ventilated lung is exposed to high strain secondary to large, nonphysiologic tidal volumes and loss of the normal functional residual capacity. In addition, the ventilated lung experiences oxidative stress, as well as capillary shear stress because of hyperperfusion. Surgical manipulation and/or resection of the collapsed lung may induce lung injury. Re-expansion of the collapsed lung at the conclusion of OLV invariably induces duration-dependent, ischemia-reperfusion injury. Inflammatory cytokines are released in response to localized injury and may promote local and contralateral lung injury. Protective ventilation and volatile anesthesia lessen the degree of injury; however, increases in biochemical and histologic markers of lung injury appear unavoidable. The endothelial glycocalyx may represent a common pathway for lung injury creation during OLV, because it is damaged by most of the recognized lung injurious mechanisms. Experimental therapies to stabilize the endothelial glycocalyx may afford the ability to reduce lung injury in the future. In the interim, protective ventilation with tidal volumes of 4 to 5 mL/kg predicted body weight, positive end-expiratory pressure of 5 to 10 cm H2O, and routine lung recruitment should be used during OLV in an attempt to minimize harmful lung stress and strain. Additional strategies to reduce lung injury include routine volatile anesthesia and efforts to minimize OLV duration and hyperoxia.

  10. Sleep in patients with restrictive lung disease.

    PubMed

    Won, Christine H J; Kryger, Meir

    2014-09-01

    Restrictive lung disease leads to ventilatory defects and diffusion impairments. These changes may contribute to abnormal nocturnal pathophysiology, including sleep architecture disruption and impaired ventilation and oxygenation. Patients with restrictive lung disease may suffer significant daytime fatigue and dysfunction. Hypercarbia and hypoxemia during sleep may impact progression of lung disease and related symptoms. Little is known about the impact of treatment of sleep disruption on sleep quality and overall prognosis in restrictive lung disease. This review discusses the pathophysiology of sleep and comorbid sleep disorders in restrictive lung diseases including interstitial lung disease, neuromuscular disease, and obesity hypoventilation syndrome. Published by Elsevier Inc.

  11. Use and abuse of lung biopsy.

    PubMed

    Gal, Anthony A

    2005-07-01

    The lung biopsy is widely recognized as a valuable tool for the diagnosis and management of diverse pulmonary disorders. The transbronchial lung biopsy, open lung biopsy, and video assisted thoracoscopic surgery biopsy are the principal tools that have been developed for obtaining lung tissue for histopathological examination. Whereas these various types of lung biopsies are highly sensitive and specific tests available for diagnosis, they may be fraught with potential problems. This review hopes to inform the reader of the indications and limitations of the lung biopsy.

  12. Neonatal opaque right lung: delayed fluid resorption

    SciTech Connect

    Swischuk, L.E.; Hayden, K.; Richardson, J.

    1981-12-01

    Eight newborn infants with opaque right lungs were examined. Clinically, the main problem associated with the opaque right lung is mild respiratory distress, and radiographyically, the findings consist of (a) a totally opaque right lung, (b) a semiopaque right lung, or (c) an opaque right upper lobe only. These findings are usually interpreted as representing pneumonia, empyema, or hydrochlothorax, but the fact that they clear within 24 to 48 hours indicates that none of these diseases is the cause. It is thought that neonatal opaque right lung results from the transient retention of normal fetal fluid in the right lung.

  13. Surgical Lung Biopsy for Interstitial Lung Diseases.

    PubMed

    Raj, Rishi; Raparia, Kirtee; Lynch, David A; Brown, Kevin K

    2017-05-01

    This review addresses common questions regarding the role of surgical lung biopsy (SLB) in the diagnosis and treatment of interstitial lung disease (ILD). We specifically address when a SLB can be diagnostic as well as when it may be avoided; for example, when the combination of the clinical context and the imaging pattern seen on high-resolution CT (HRCT) chest scans can provide a confident diagnosis. Existing studies on the diagnostic utility as well as the complications associated with SLB are reviewed; also reviewed are the performance characteristics and reliability of HRCT scans of the chest in predicting the underlying histopathologic findings of the lung. The review is formatted in the form of answers to questions that clinicians regularly ask when considering an SLB in a patient with ILD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  14. [Lung resection for lung carcinoma with idiopathic interstitial pneumonia].

    PubMed

    Nakagawa, K; Yasumitsu, T; Kotake, Y; Ueshima, S; Kazuo, H; Tanemura, M; Hirabayashi, H; Ogawa, T

    1994-10-01

    Of 12 patients who underwent lung resections for lung cancer with idiopathic interstitial pneumonia (IIP), eight patients survived and four patients died due to acute exacerbation of IIP after the operation. The preoperative values for percent forced vital capacity, predicted postoperative percent vital capacity, percent one-second forced expiratory volume index and serum level of C-reactive protein were significantly different between the group of patients who survived and that of having died. Three days after the operation, the percentage of lymphocytes among leukocytes and serum level of lactate dehydrogenase in the two groups were both significantly different. These findings showed that the operative strategy for patients with lung cancer and IIP needs specifically careful consideration for operative procedure, and preoperative serum levels of C-reactive protein and postoperative lactate dehydrogenase and the percentage of lymphocytes in leukocytes would be useful in evaluation of the severity of IIP.

  15. Starting a Lung Transplant Program

    PubMed Central

    Eberlein, Michael; Geist, Lois; Keech, John; Zabner, Joseph; Gruber, Peter J.; Iannettoni, Mark D.; Parekh, Kalpaj

    2015-01-01

    Lung transplantation is an effective therapy for many patients with end-stage lung disease. Few centers across the United States offer this therapy, as a successful lung transplant program requires significant institutional resources and specialized personnel. Analysis of the United Network of Organ Sharing database reveals that the failure rate of new programs exceeds 40%. These data suggest that an accurate assessment of program viability as well as a strategy to continuously assess defined quality measures is needed. As part of strategic planning, regional availability of recipient and donors should be assessed. Additionally, analysis of institutional expertise at the physician, support staff, financial, and administrative levels is necessary. In May of 2007, we started a new lung transplant program at the University of Iowa Hospitals and Clinics and have performed 101 transplants with an average recipient 1-year survival of 91%, placing our program among the top in the country for the past 5 years. Herein, we review internal and external factors that impact the viability of a new lung transplant program. We discuss the use of four prospectively identified quality measures: volume, recipient outcomes, financial solvency, and academic contribution as one approach to achieve programmatic excellence. PMID:25940255

  16. Ventilator-induced Lung Injury

    PubMed Central

    Kneyber, Martin C. J.; Zhang, Haibo; Slutsky, Arthur S.

    2016-01-01

    It is well established that mechanical ventilation can injure the lung, producing an entity known as ventilator-induced lung injury (VILI). There are various forms of VILI, including volutrauma (i.e., injury caused by overdistending the lung), atelectrauma (injury due to repeated opening/closing of lung units), and biotrauma (release of mediators that can induce lung injury or aggravate pre-existing injury, potentially leading to multiple organ failure). Experimental data in the pediatric context are in accord with the importance of VILI, and appear to show age-related susceptibility to VILI, although a conclusive link between use of large Vts and mortality has not been demonstrated in this population. The relevance of VILI in the pediatric intensive care unit population is thus unclear. Given the physiological and biological differences in the respiratory systems of infants, children, and adults, it is difficult to directly extrapolate clinical practice from adults to children. This Critical Care Perspective analyzes the relevance of VILI to the pediatric population, and addresses why pediatric patients might be less susceptible than adults to VILI. PMID:25003705

  17. Targeted Therapies for Lung Cancer

    PubMed Central

    Larsen, Jill E.; Cascone, Tina; Gerber, David E.; Heymach, John V.; Minna, John D.

    2012-01-01

    Although lung cancer remains the leading cancer killer in the United States, recently a number of developments indicate future clinical benefit. These include evidence that computed tomography–based screening decreases lung cancer mortality, the use of stereotactic radiation for early-stage tumors, the development of molecular methods to predict chemotherapy sensitivity, and genome-wide expression and mutation analysis data that have uncovered oncogene “addictions” as important therapeutic targets. Perhaps the most significant advance in the treatment of this challenging disease is the introduction of molecularly targeted therapies, a term that currently includes monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The development of effective targeted therapeutics requires knowledge of the genes and pathways involved and how they relate to the biologic behavior of lung cancer. Drugs targeting the epidermal growth factor receptor, anaplastic lymphoma kinase, and vascular endothelial growth factor are now U.S. Food and Drug Administration approved for the treatment of advanced non-small cell lung cancer. These agents are generally better tolerated than conventional chemotherapy and show dramatic efficacy when their use is coupled with a clear understanding of clinical data, mechanism, patient selection, drug interactions, and toxicities. Integrating genome-wide tumor analysis with drug- and targeted agent-responsive phenotypes will provide a wealth of new possibilities for lung cancer–targeted therapeutics. Ongoing research efforts in these areas as well as a discussion of emerging targeted agents being evaluated in clinical trials are the subjects of this review. PMID:22157296

  18. Molecular diagnosis in lung diseases.

    PubMed

    Calabrese, Fiorella; Lunardi, Francesca; Popper, Helmut

    2015-01-01

    The development of different molecular biology techniques in the past decade has led to an explosion of new research in molecular pathology with consequent important applications to diagnosis, prognosis, and therapeutics, as well as a clearer concept of the disease pathogenesis. Many methods used in molecular pathology are now validated and used in several areas of pathological diagnosis, particularly on infectious and neoplastic diseases. The spectrum of infectious diseases, especially lung infective diseases, is now broadening and modifying, thus the pathologist is increasingly involved in the diagnosis of these pathologies. The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms of prognosis and therapy. This review focuses on molecular pathology of the principal infective lung diseases and tumors.

  19. Lung function in insulation workers.

    PubMed

    Clausen, J; Netterstrøm, B; Wolff, C

    1993-03-01

    To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease.

  20. Spectrum of fibrosing diffuse parenchymal lung disease.

    PubMed

    Morgenthau, Adam S; Padilla, Maria L

    2009-02-01

    The interstitial lung diseases are a heterogeneous group of disorders characterized by inflammation and/or fibrosis of the pulmonary interstitium. In 2002, the American Thoracic Society and the European Respiratory Society revised the classification of interstitial lung diseases and introduced the term diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are a subtype of diffuse parenchymal lung disease. The idiopathic interstitial pneumonias are subdivided into usual interstitial pneumonia (with its clinical counterpart idiopathic interstitial pneumonia), nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, acute interstitial pneumonia, desquamative interstitial pneumonia, respiratory bronchiolitis interstitial lung disease, and lymphocytic pneumonia. Sarcoidosis and hypersensitivity pneumonitis are the 2 most common granulomatous diffuse parenchymal lung diseases. Rheumatoid arthritis, systemic sclerosis, and dermatomyositis/polymyositis (causing antisynthetase syndrome) are diffuse parenchymal lung diseases of known association because these conditions are associated with connective tissue disease. Hermansky-Pudlak syndrome is a rare genetic diffuse parenchymal lung disease characterized by the clinical triad of pulmonary disease, oculocutaneous albinism, and bleeding diathesis. This review provides an overview of the chronic fibrosing diffuse parenchymal lung diseases. Its primary objective is to illuminate the clinical challenges encountered by clinicians who manage the diffuse parenchymal lung diseases regularly and to offer potential solutions to those challenges. Treatment for the diffuse parenchymal lung diseases is limited, and for many patients with end-stage disease, lung transplantation remains the best option. Although much has been learned about the diffuse parenchymal lung diseases during the past decade, research in these diseases is urgently needed.

  1. Cytogenetic and molecular aspects of lung cancer.

    PubMed

    Panani, Anna D; Roussos, Charis

    2006-07-28

    Lung cancer is one of the most common cancers worldwide and its pathogenesis is closely associated with tobacco smoking. Continuous exposure of smoking carcinogens results in the accumulation of several alterations of tumorigenesis related genes leading to neoplastic bronchial lesions. Lung cancer is divided in two main histological groups, non-small cell lung carcinomas (NSCLCs) and small cell lung carcinomas (SCLCs). It seems that lung tumorigenesis is a multistep process in which a number of genetic events including alterations of oncogenes and tumor suppressor genes have been occurred. Cytogenetic abnormalities in lung cancer are very complex. However, a number of recurrent cytogenetic abnormalities have been identified. Many of these changes are common in both major histological groups of lung cancer while certain chromosomal abnormalities have been correlated with the stage or the grade of the tumors. In addition, several molecular alterations have been constantly found. Some of them are common in different histological subtypes of lung cancer and they appear to play an important role in the pathogenesis of lung cancer. A good understanding of the underlying genetic changes of lung tumorigenesis will provide new perspectives for early diagnosis and screening of high-risk individuals. In addition, a number of genetical prognostic factors have been identified as possibly helpful parameters in the evaluation of lung cancer patients. Further research is required in order to systematically investigate genetical alterations in lung cancer contributing to improvement of lung cancer classification and staging and to development of new molecular targeted therapies.

  2. What Are the Key Statistics for Lung Carcinoid Tumors?

    MedlinePlus

    ... Carcinoid Tumors What Are the Key Statistics About Lung Carcinoid Tumors? About 1% to 2% of all ... Lung Carcinoid Tumor Research and Treatment? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  3. What Are the Risk Factors for Lung Carcinoid Tumors?

    MedlinePlus

    ... and Prevention What Are the Risk Factors for Lung Carcinoid Tumors? A risk factor is anything that ... Can Lung Carcinoid Tumors Be Prevented? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  4. What Should You Ask Your Doctor about Lung Carcinoid Tumors?

    MedlinePlus

    ... Staging What Should You Ask Your Doctor About Lung Carcinoid Tumors? It is important to have honest, ... Your Doctor About Lung Carcinoid Tumors? More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  5. What Happens after Treatment for Lung Carcinoid Tumors?

    MedlinePlus

    ... Tumor After Treatment What Happens After Treatment for Lung Carcinoid Tumors? For many people with carcinoid tumors, ... Lung Carcinoid Tumor Treatment Stops Working More In Lung Carcinoid Tumors About Lung Carcinoid Tumors Causes, Risk ...

  6. Functional imaging in lung cancer

    PubMed Central

    Harders, S W; Balyasnikowa, S; Fischer, B M

    2014-01-01

    Lung cancer represents an increasingly frequent cancer diagnosis worldwide. An increasing awareness on smoking cessation as an important mean to reduce lung cancer incidence and mortality, an increasing number of therapy options and a steady focus on early diagnosis and adequate staging have resulted in a modestly improved survival. For early diagnosis and precise staging, imaging, especially positron emission tomography combined with CT (PET/CT), plays an important role. Other functional imaging modalities such as dynamic contrast-enhanced CT (DCE-CT) and diffusion-weighted MR imaging (DW-MRI) have demonstrated promising results within this field. The purpose of this review is to provide the reader with a brief and balanced introduction to these three functional imaging modalities and their current or potential application in the care of patients with lung cancer. PMID:24289258

  7. Farmer's lung disease in Somerset.

    PubMed Central

    Pether, J V; Greatorex, F B

    1976-01-01

    A survey of laboratory records was made to assess the value of the precipitin test and isolation methods in the diagnosis of farmer's lung disease and also to determine its prevalence in the farming population of Somerset. A link was established between the clinical diagnosis as written on the form that accompanied the specimen and the actual number of positive laboratory diagnoses made. Fifty (43%) of the clinically diagnosed patients were serologically positive for farmer's lung during a four-year period. If the clinically diagnosed but serologically negative cases of farmer's lung disease are added to this number, a prevalence of about 23 per 1000 of the farming population of Somerset is obtained. PMID:999800

  8. Drug Induced Interstitial Lung Disease

    PubMed Central

    Schwaiblmair, Martin; Behr, Werner; Haeckel, Thomas; Märkl, Bruno; Foerg, Wolfgang; Berghaus, Thomas

    2012-01-01

    With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease. PMID:22896776

  9. Lung Macrophage Diversity and Asthma

    PubMed Central

    2016-01-01

    Macrophages (MPs) are one of the most prominent leukocyte populations in the lung and, in many ways, a forgotten player in asthma pathogenesis. Diverse functions in asthma initiation and maintenance in chronic disease have been demonstrated, which has led to confusion as to if pulmonary MPs are agents of good or evil in asthma. Much of this is due to the wide diversity of MP populations in the lung, many of which are inaccessible experimentally in most clinical studies. This review frames lung MP biology in the context of location, phenotype, function, and response phase in asthma pathogenesis. It also assesses new findings regarding MP diversity that have challenged old dogmas and generates new ways to understand how MPs function. PMID:27027949

  10. Cilia Dysfunction in Lung Disease

    PubMed Central

    Tilley, Ann E.; Walters, Matthew S.; Shaykhiev, Renat; Crystal, Ronald G.

    2015-01-01

    A characteristic feature of the human airway epithelium is the presence of ciliated cells bearing motile cilia, specialized cell surface projections containing axonemes comprised of microtubules and dynein arms, which provide ATP-driven motility. In the airways, cilia function in concert with airway mucus to mediate the critical function of mucociliary clearance, cleansing the airways of inhaled particles and pathogens. The prototypical disorder of respiratory cilia is primary ciliary dyskinesia, an inherited disorder that leads to impaired mucociliary clearance, repeated chest infections, and progressive destruction of lung architecture. Numerous acquired lung diseases are also marked by abnormalities in both cilia structure and function. In this review we summarize current knowledge regarding airway ciliated cells and cilia, how they function to maintain a healthy epithelium, and how disorders of cilia structure and function contribute to inherited and acquired lung disease. PMID:25386990

  11. Lung cancer in elderly patients

    PubMed Central

    Diso, Daniele; Onorati, Ilaria; Anile, Marco; Mantovani, Sara; Rendina, Erino A.

    2016-01-01

    There is a worldwide-accepted evidence of a population shift toward older ages. This shift favors an increased risk of developing lung cancer that is primarily a disease of older populations. Decision making is extremely difficult in elderly patients, since this group is under-represented in clinical trials with only 25% of them historically opening to patients older than 65 years. For all these reasons, a “customized” preoperative assessment to identify physiological or pathological frailty should be encouraged since standard tools may be less reliable. The work already done to improve patient selection for lung surgery in the elderly population clearly shows that surgical resection seems the treatment of choice for early stage lung cancer. Further studies are required to improve outcome by reducing postoperative morbidity and mortality. PMID:27942414

  12. Impacts of Exercise on Prognostic Biomarkers in Lung Cancer Patients

    ClinicalTrials.gov

    2016-02-18

    Extensive Stage Small Cell Lung Cancer; Healthy, no Evidence of Disease; Limited Stage Small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Recurrent Small Cell Lung Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  13. Lung Cancer Epidemiology in Korea.

    PubMed

    Shin, Aesun; Oh, Chang-Mo; Kim, Byung-Woo; Woo, Hyeongtaek; Won, Young-Joo; Lee, Jin-Soo

    2017-07-01

    The current study was undertaken to examine the trends in the lung cancer incidence, mortality, and survival after a diagnosis in Korea. Lung cancer incidence data according to the histologic type and mortality data were obtained from the Korea Central Cancer Registry and the Statistics Korea, respectively. The age-standardized incidence and mortality rates were calculated, and the Joinpoint model and age-period-cohort analyses were used to describe the trends in the rates. The 5-year relative survival rates of lung cancer were also calculated. Although the number of new lung cancer cases increased between 1999 and 2012, the age-standardized incidence rate decreased by 0.9% per year in men, whereas the incidence in women increased by 1.7% per year over the same time. Until 2010, the most common histologic type in men was squamous cell carcinoma, then adenocarcinoma prevailed thereafter. Since 1999, the most frequent histological type in women was adenocarcinoma. The lung cancer mortality started to decrease in 2002, with a more apparent decline for the younger age groups in both men and women. Overall, the 5-year relative survival rates have improved significantly from 11.2% for men and 14.7% for women among patients diagnosed between 1993 and 1997 to 19.3% for men and 28.2% for women among patients diagnosed between 2008 and 2012, respectively. An improvement in survival rate was observed for all major histology groups. The epidemiology of lung cancer in Korea has changed over a short time span, with decreasing mortality and improving survival rates. Further study is warranted to determine the cause of these changes.

  14. Risk Profiling May Improve Lung Cancer Screening

    Cancer.gov

    A new modeling study suggests that individualized, risk-based selection of ever-smokers for lung cancer screening may prevent more lung cancer deaths and improve the effectiveness and efficiency of screening compared with current screening recommendations

  15. Quick-Relief Medications for Lung Diseases

    MedlinePlus

    ... relief medications are used to treat asthma, other lung disease symptoms or an acute episode (such as an ... about the following quick-relief asthma and other lung disease medications: Anticholinergics Anticholinergics are quick-relief asthma and ...

  16. Ebola Can Linger in Lungs, Study Finds

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_162904.html Ebola Can Linger in Lungs, Study Finds Discovery in ... Researchers say they've discovered signs that the Ebola virus could lurk in the lungs and reproduce ...

  17. Suicide Risk Quadruples After Lung Cancer Diagnosis

    MedlinePlus

    ... news/fullstory_165864.html Suicide Risk Quadruples After Lung Cancer Diagnosis Doctors, loved ones need to be on ... TUESDAY, May 23, 2017 (HealthDay News) -- People with lung cancer have a strikingly higher-than-normal risk of ...

  18. Clinical neurology in lung transplantation.

    PubMed

    Wigfield, Christopher H; Love, Robert B

    2014-01-01

    Lung transplantation is the only established therapeutic option for several end-stage respiratory diseases. Limited mostly by lack of suitable allografts, the results have measurably improved over the last decade. Numerous surgical and pharmaceutical improvements have had positive impact on outcomes. The potential for critical care issues and the need for interdisciplinary management remains paramount. Cardiac, renal, and metabolic complications are frequently encountered in the acute postoperative phase. Allograft rejection and infectious diseases as well as problems related to immunosuppressive regimen are seen later after lung transplantation. Neurologic manifestations with a range of etiologies are discussed here in this context.

  19. Cigarette smoke and lung cancer

    SciTech Connect

    Martonen, T.B.; Hofmann, W.; Lowe, J.E.

    1987-01-01

    Cigarette smoke has been implicated in a causal relationship with carcinoma of the lung. An intriguing feature of the disease is the site-selectivity with which bronchogenic cancer manifests itself; most cancers are detected in the main, lobar and segmental bronchi, perhaps specifically at airway bifurcations. The elevated risk of lung cancer to smokers may result from a complex interplay between smoking and exposure to ambient Rn progeny, including the promotional-effect role (as opposed to being the initiating event) of cigarette smoke in tumor development. It has been determined that smokers exposed to average indoor Rn progency levels receive surprisingly high doses at hot spots within bronchial bifurcations.

  20. Airway complications after lung transplantation.

    PubMed

    Machuzak, Michael; Santacruz, Jose F; Gildea, Thomas; Murthy, Sudish C

    2015-01-01

    Airway complications after lung transplantation present a formidable challenge to the lung transplant team, ranging from mere unusual images to fatal events. The exact incidence of complications is wide-ranging depending on the type of event, and there is still evolution of a universal characterization of the airway findings. Management is also wide-ranging. Simple observation or simple balloon bronchoplasty is sufficient in many cases, but vigilance following more severe necrosis is required for late development of both anastomotic and nonanastomotic airway strictures. Furthermore, the impact of coexisting infection, rejection, and medical disease associated with high-level immunosuppression further complicates care.

  1. Occupational exposure and lung cancer

    PubMed Central

    Spyratos, Dionysios; Porpodis, Konstantinos; Tsakiridis, Kosmas; Machairiotis, Nikolaos; Katsikogiannis, Nikolaos; Kougioumtzi, Ioanna; Dryllis, Georgios; Kallianos, Anastasios; Rapti, Aggeliki; Li, Chen; Zarogoulidis, Konstantinos

    2013-01-01

    Lung cancer is the leading cause of cancer death for male and the second most usual cancer for women after breast cancer. Currently there are available several non-specific cytotoxic agents and several targeted agents for lung cancer therapy. However; early stage diagnosis is still unavailable and several efforts are being made towards this direction. Novel biomarkers are being investigated along with new biopsy techniques. The occupational and environmental exposure to carcinogenic agents is an everyday phenomenon. Therefore until efficient early diagnosis is available, avoidance of exposure to carcinogenic agents is necessary. In the current mini-review occupational and environmental carcinogenic agents will be presented. PMID:24102018

  2. Lung Cancer and Eye Metastases

    PubMed Central

    Lampaki, Sofia; Kioumis, Ioannis; Pitsiou, Georgia; Lazaridis, George; Syrigos, Konstantinos; Trakada, Georgia; Kakolyris, Stylianos; Zarogoulidis, Konstantinos; Mpoukovinas, Ioannis; Rapti, Aggeliki; Zarogoulidis, Paul

    2014-01-01

    It has been observed that lung cancer either non-small cell or small cell is responsible for eye metastases. This form of metastases in several cases was the first manifestation of the disease and further investigation led to the diagnosis of the underlying malignancy. Both types of lung cancer are equally responsible for this demonstration. Furthermore; both chemotherapy and tyrosine kinase inhibitors have shown equal positive results in treating the exophalmos manifestation. Up to date information will be presented in our current work. PMID:25738158

  3. Complement System in Lung Disease

    PubMed Central

    Pandya, Pankita H.

    2014-01-01

    In addition to its established contribution to innate immunity, recent studies have suggested novel roles for the complement system in the development of various lung diseases. Several studies have demonstrated that complement may serve as a key link between innate and adaptive immunity in a variety of pulmonary conditions. However, the specific contributions of complement to lung diseases based on innate and adaptive immunity are just beginning to emerge. Elucidating the role of complement-mediated immune regulation in these diseases will help to identify new targets for therapeutic interventions. PMID:24901241

  4. Lung flooding enables efficient lung sonography and tumour imaging in human ex vivo and porcine in vivo lung cancer model

    PubMed Central

    2013-01-01

    Background Sonography has become the imaging technique of choice for guiding intraoperative interventions in abdominal surgery. Due to artefacts from residual air content, however, videothoracoscopic and open intraoperative ultrasound-guided thermoablation of lung malignancies are impossible. Lung flooding is a new method that allows complete ultrasound imaging of lungs and their tumours. Methods Fourteen resected tumourous human lung lobes were examined transpleurally with B-mode ultrasound before (in atelectasis) and after lung flooding with isotonic saline solution. In two swine, the left lung was filled with 15 ml/kg isotonic saline solution through the left side of a double-lumen tube. Lung tumours were simulated by transthoracic ultrasound-guided injection of 5 ml of purified bovine serum albumin in glutaraldehyde, centrally into the left lower lung lobe. The rate of tumour detection, the severity of disability caused by residual gas, and sonomorphology of the lungs and tumours were assessed. Results The ex vivo tumour detection rate was 100% in flooded human lung lobes and 43% (6/14) in atelectatic lungs. In all cases of atelectasis, sonographic tumour imaging was impaired by residual gas. Tumours and atelectatic tissue were isoechoic. In 28% of flooded lungs, a little residual gas was observed that did not impair sonographic tumour imaging. In contrast to tumours, flooded lung tissue was hyperechoic, homogeneous, and of fine-grained structure. Because of the bronchial wall three-laminar structure, sonographic differentiation of vessels and bronchi was possible. In all cases, malignant tumours in the flooded lung appeared well-demarcated from the lung parenchyma. Adenocarcinoma, squamous, and large cell carcinomas were hypoechoic. Bronchioloalveolar cell carcinoma was slightly hyperechoic. Transpleural sonography identifies endobronchial tumour growth and bronchial wall destruction. With transthoracic sonography, the flooded animal lung can be completely

  5. Pulmonary Rehabilitation in Improving Lung Function in Patients With Locally Advanced Non-Small Cell Lung Cancer Undergoing Chemoradiation

    ClinicalTrials.gov

    2017-04-12

    Cachexia; Fatigue; Pulmonary Complications; Radiation Toxicity; Recurrent Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

  6. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    PubMed

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  7. Mechanisms of ventilator-induced lung injury in healthy lungs.

    PubMed

    Silva, Pedro Leme; Negrini, Daniela; Rocco, Patricia Rieken Macêdo

    2015-09-01

    Mechanical ventilation is an essential method of patient support, but it may induce lung damage, leading to ventilator-induced lung injury (VILI). VILI is the result of a complex interplay among various mechanical forces that act on lung structures, such as type I and II epithelial cells, endothelial cells, macrophages, peripheral airways, and the extracellular matrix (ECM), during mechanical ventilation. This article discusses ongoing research focusing on mechanisms of VILI in previously healthy lungs, such as in the perioperative period, and the development of new ventilator strategies for surgical patients. Several experimental and clinical studies have been conducted to evaluate the mechanisms of mechanotransduction in each cell type and in the ECM, as well as the role of different ventilator parameters in inducing or preventing VILI. VILI may be attenuated by reducing the tidal volume; however, the use of higher or lower levels of positive end-expiratory pressure (PEEP) and recruitment maneuvers during the perioperative period is a matter of debate. Many questions concerning the mechanisms of VILI in surgical patients remain unanswered. The optimal threshold value of each ventilator parameter to reduce VILI is also unclear. Further experimental and clinical studies are necessary to better evaluate ventilator settings during the perioperative period in different types of surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Clinical review: Bedside lung ultrasound in critical care practice

    PubMed Central

    Bouhemad, Bélaïd; Zhang, Mao; Lu, Qin; Rouby, Jean-Jacques

    2007-01-01

    Lung ultrasound can be routinely performed at the bedside by intensive care unit physicians and may provide accurate information on lung status with diagnostic and therapeutic relevance. This article reviews the performance of bedside lung ultrasound for diagnosing pleural effusion, pneumothorax, alveolar-interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/derecruitment in critically ill patients with acute lung injury. PMID:17316468

  9. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation.

  10. Histopathologic approach to the surgical lung biopsy in interstitial lung disease.

    PubMed

    Jones, Kirk D; Urisman, Anatoly

    2012-03-01

    Interpretation of lung biopsy specimens is an integral part in the diagnosis of interstitial lung disease (ILD). The process of evaluating a surgical lung biopsy for disease involves answering several questions. Unlike much of surgical pathology of neoplastic lung disease, arriving at the correct diagnosis in nonneoplastic lung disease often requires correlation with clinical and radiologic findings. The topic of ILD or diffuse infiltrative lung disease covers several hundred entities. This article is meant to be a launching point in the clinician's approach to the histologic evaluation of lung disease. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. The Therapeutic Potential of Differentiated Lung Cells from Embryonic Stem Cells in Lung Diseases.

    PubMed

    Mokhber Dezfouli, Mohammad Reza; Chaleshtori, Sirous Sadeghian; Dehghan, Mohammad Mehdi; Tavanaeimanesh, Hamid; Baharvand, Hossein; Tahamtani, Yaser

    2017-01-01

    Lung diseases cause great morbidity and mortality. The choice of effective medical treatment is limited and the number of lung diseases are difficult to treat with current treatments. The embryonic stem cells (ESCs) have the potential to differentiate into cell types of all three germinal layers, including lung epithelial cells. So they can be a potential source for new cell therapies for hereditary or acquired diseases of the airways and lungs. One method for treatment of lung diseases is cell therapy and the use of ESCs that can replace the damaged epithelial and endothelial cells. Progress using ESCs has developed slowly for lung regeneration because differentiation of lung cells from ESCs is more difficult as compared to differentiation of other cells. The review studies the therapeutic effects of differentiated lung cells from embryonic stem cells in lung diseases. There are few studies of differentiation of ESCs into a lineage of respiratory and then investigation of this cell in experimental model of lung diseases.

  12. One-lung overventilation does not induce inflammation in the normally ventilated contralateral lung.

    PubMed

    Almendros, Isaac; Gutierrez, Patricia T; Closa, Daniel; Navajas, Daniel; Farre, Ramon

    2008-06-30

    The aim was to assess whether induction of ventilator-induced lung injury (VILI) in one lung triggers a concomitant inflammatory response in the normally ventilated contralateral lung. To this end, a differential ventilator was used in 6 rats. One lung was normally ventilated (3.5 ml/kg b.w.) and the contralateral lung was overstretched (15 ml/kg b.w.). Six control rats were normally ventilated (3.5 ml/kg b.w. each lung). After 3h, edema and gene expression of MIP-2 in the lung, and plasma and liver TNF-alpha were assessed. Overexpression of MIP-2 and edema were found in the overventilated lung but not in the normally ventilated contralateral lung. No detectable levels of circulating and liver TNF-alpha were detected. These data do not support the hypothesis of an early positive feedback in the lung inflammation during the mechanical ventilation.

  13. Nicotine transport in lung and non-lung epithelial cells.

    PubMed

    Takano, Mikihisa; Kamei, Hidetaka; Nagahiro, Machi; Kawami, Masashi; Yumoto, Ryoko

    2017-11-01

    Nicotine is rapidly absorbed from the lung alveoli into systemic circulation during cigarette smoking. However, mechanism underlying nicotine transport in alveolar epithelial cells is not well understood to date. In the present study, we characterized nicotine uptake in lung epithelial cell lines A549 and NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Characteristics of [(3)H]nicotine uptake was studied using these cell lines. Nicotine uptake in A549 cells occurred in a time- and temperature-dependent manner and showed saturation kinetics, with a Km value of 0.31mM. Treatment with some organic cations such as diphenhydramine and pyrilamine inhibited nicotine uptake, whereas treatment with organic cations such as carnitine and tetraethylammonium did not affect nicotine uptake. Extracellular pH markedly affected nicotine uptake, with high nicotine uptake being observed at high pH up to 11.0. Modulation of intracellular pH with ammonium chloride also affected nicotine uptake. Treatment with valinomycin, a potassium ionophore, did not significantly affect nicotine uptake, indicating that nicotine uptake is an electroneutral process. For comparison, we assessed the characteristics of nicotine uptake in another lung epithelial cell line NCI-H441 and in non-lung epithelial cell lines HepG2 and MCF-7. Interestingly, these cell lines showed similar characteristics of nicotine uptake with respect to pH dependency and inhibition by various organic cations. The present findings suggest that a similar or the same pH-dependent transport system is involved in nicotine uptake in these cell lines. A novel molecular mechanism of nicotine transport is proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Diffuse lung diseases in cigarette smokers.

    PubMed

    Vassallo, Robert

    2012-10-01

    Cigarette smoking is a recognized causative agent or precipitant of specific diffuse lung diseases characterized by bronchiolar and interstitial lung inflammation. Respiratory bronchiolitis-associated interstitial lung disease and pulmonary Langerhans cell histiocytosis are now considered smoking-induced diffuse lung diseases. Desquamative interstitial pneumonia is also recognized as a smoking-induced interstitial pneumonia in most cases. These disorders affect relatively young adult smokers and may be progressive. Although distinguishable by histopathological and radiographic features, significant overlap occurs in many cases with chest radiography and lung histology showing overlapping features of smoking-related bronchiolar and interstitial lung injury. Cigarette smoking is also recognized as an important precipitant of many acute eosinophilic pneumonia cases. Smokers are at higher risk of developing fibrotic interstitial lung diseases such as idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease. Certain smokers also develop combined emphysema and lung fibrosis. The avoidance of primary and second-hand cigarette smoke is a critical component of management for patients afflicted with these smoking-induced diffuse lung diseases. The role of corticosteroids and other immunosuppressive treatments in the management of smoking-related interstitial lung diseases remains poorly defined and should be reserved for individuals with progressive disease despite smoking cessation. Understanding mechanisms by which tobacco induces diffuse lung pathology is critical in the pursuit of novel therapeutic approaches for these diseases. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Clinical and experimental pathology of lung cancer

    SciTech Connect

    McVie, J.G.; Bakker, W.; Wagenaar, S.C.; Carney, D.

    1986-01-01

    This book contains 17 selections. Some of the titles are: Flow cytometric DNA analysis in the study of small cell carcinoma of the lung; Mechanisms of oncogenesis; Adhesion mechanisms in liver metastasis; Current concepts in the therapy of small cell lung cancer; Application of monoclonal antibodies in imaging and therapy; and Clinical applications of the biologic properties of small cell lung cancer.

  16. [ENDOSCOPIC LUNG VOLUME REDUCTION IN PULMONARY EMPHYSEMA].

    PubMed

    Duysinx, B; Heinen, V; Louis, R; Corhay, J-L

    2015-12-01

    Emphysema is characterized by an irreversible alveolar destruction, a progressive lung hyperinflation and a dysfunction of respiratory muscles. It induces a respiratory functional limitation and a decrease of quality of life. Endoscopic lung volume reduction represents a potential alternative to surgical treatments for advanced heterogeneous emphysema without concomitant surgical morbidity. The different bronchoscopic systems for lung volume reduction currently under evaluation are presented.

  17. Lung computed tomography during a lung recruitment maneuver in patients with acute lung injury.

    PubMed

    Bugedo, Guillermo; Bruhn, Alejandro; Hernández, Glenn; Rojas, Gonzalo; Varela, Cristián; Tapia, Juan Carlos; Castillo, Luis

    2003-02-01

    To assess the acute effect of a lung recruitment maneuver (LRM) on lung morphology in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Ten patients with ALI/ARDS on mechanical ventilation. Prospective clinical study. Computed tomography (CT) scan facility in a teaching hospital. An LRM performed by stepwise increases in positive end-expiratory pressure (PEEP) of up to 30-40 cm H(2)O. Lung basal CT sections were taken at end-expiration (patients 1 to 5), and at end-expiration and end-inspiration (patients 6 to 10). Arterial blood gases and static compliance (C(st)) were measured before, during and after the LRM. Poorly aerated and non-aerated tissue at PEEP 10 cm H(2)O accounted for 60.0+/-29.1% of lung parenchyma, while only 1.1+/-1.8% was hyperinflated. Increasing PEEP to 20 and 30 cm H(2)O, compared to PEEP 10 cm H(2)O, decreased poorly aerated and non-aerated tissue by 16.2+/-28.0% and 33.4+/-13.8%, respectively ( p<0.05). This was associated with an increase in PaO(2) and a decrease in total static compliance. Inspiration increased alveolar recruitment at all PEEP levels. Hyperinflated tissue increased up to 2.9+/-4.0% with PEEP 30 cm H(2)O, and to a lesser degree with inspiration. No barotrauma or severe hypotension occurred. Lung recruitment maneuvers improve oxygenation by expanding collapsed alveoli without inducing too much hyperinflation in ALI/ARDS patients. An LRM during the CT scan gives morphologic and functional information that could be useful in setting ventilatory parameters.

  18. 9 CFR 325.8 - Transportation and other transactions concerning certain undenatured lungs or lung lobes from...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions... transactions concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions and restrictions. (a) Lungs or lung lobes, other than those condemned under § 310.16(b) of...

  19. 9 CFR 325.8 - Transportation and other transactions concerning certain undenatured lungs or lung lobes from...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions... transactions concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions and restrictions. (a) Lungs or lung lobes, other than those condemned under § 310.16(b) of...

  20. 9 CFR 325.8 - Transportation and other transactions concerning certain undenatured lungs or lung lobes from...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions... transactions concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions and restrictions. (a) Lungs or lung lobes, other than those condemned under § 310.16(b) of...

  1. 9 CFR 325.8 - Transportation and other transactions concerning certain undenatured lungs or lung lobes from...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions... transactions concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions and restrictions. (a) Lungs or lung lobes, other than those condemned under § 310.16(b) of...

  2. 9 CFR 325.8 - Transportation and other transactions concerning certain undenatured lungs or lung lobes from...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions... transactions concerning certain undenatured lungs or lung lobes from official establishments or in commerce; provisions and restrictions. (a) Lungs or lung lobes, other than those condemned under § 310.16(b) of...

  3. [Lung cancer and lymph drainage].

    PubMed

    Riquet, M

    2007-01-01

    Lung cancer is lymphophile and may involve lymph nodes (LN) belonging to lung lymph drainage. LN metastases are figured within stations numbered 1 to 14. These stations are located along lymph vessels. The lymph vessels and the LN are forming together anatomical chains. Lymph vessels are valved and pulsatile and travel to the cervical venous confluence where they pour the lung lymph into the blood circulation. They may be totally or partly nodeless along their travel, anastomose with each other around the trachea, and connect with the thoracic duct within the mediastinum. Within the anatomical LN chains, LN are variable in number and in size from one individual to another. They may be absent from one or several stations of the international mapping. Stations are located along the anatomical chains: pulmonary ligament (9), tracheal bifurcation(8 and 7), right paratracheal (4R, 2R and 1), preaortic (5 and 6), left paratracheal (4L, 2L and 1). Station 3 is located on 2 differents chains (phrenic and right esophagotracheal). Station 10 are located at the beginning of the mediastinal lymph nodes chains. Each chain connects with the blood circulation, anastomoses with he neighbouring chains and behave as an own entity whatever the number of its LN. International station mapping misknowns this anatomy and occults the true pronostic value of lung lymph drainage.

  4. Probabilistic Elastography: Estimating Lung Elasticity

    PubMed Central

    Risholm, Petter; Ross, James; Washko, George R.; Wells, William M.

    2011-01-01

    We formulate registration-based elastography in a probabilistic framework and apply it to study lung elasticity in the presence of emphysematous and fibrotic tissue. The elasticity calculations are based on a Finite Element discretization of a linear elastic biomechanical model. We marginalize over the boundary conditions (deformation) of the biomechanical model to determine the posterior distribution over elasticity parameters. Image similarity is included in the likelihood, an elastic prior is included to constrain the boundary conditions, while a Markov model is used to spatially smooth the inhomogeneous elasticity. We use a Markov Chain Monte Carlo (MCMC) technique to characterize the posterior distribution over elasticity from which we extract the most probable elasticity as well as the uncertainty of this estimate. Even though registration-based lung elastography with inhomogeneous elasticity is challenging due the problem's highly underdetermined nature and the sparse image information available in lung CT, we show promising preliminary results on estimating lung elasticity contrast in the presence of emphysematous and fibrotic tissue. PMID:21761697

  5. Probabilistic elastography: estimating lung elasticity.

    PubMed

    Risholm, Petter; Ross, James; Washko, George R; Wells, William M

    2011-01-01

    We formulate registration-based elastography in a probabilistic framework and apply it to study lung elasticity in the presence of emphysematous and fibrotic tissue. The elasticity calculations are based on a Finite Element discretization of a linear elastic biomechanical model. We marginalize over the boundary conditions (deformation) of the biomechanical model to determine the posterior distribution over elasticity parameters. Image similarity is included in the likelihood, an elastic prior is included to constrain the boundary conditions, while a Markov model is used to spatially smooth the inhomogeneous elasticity. We use a Markov Chain Monte Carlo (MCMC) technique to characterize the posterior distribution over elasticity from which we extract the most probable elasticity as well as the uncertainty of this estimate. Even though registration-based lung elastography with inhomogeneous elasticity is challenging due the problem's highly underdetermined nature and the sparse image information available in lung CT, we show promising preliminary results on estimating lung elasticity contrast in the presence of emphysematous and fibrotic tissue.

  6. Lung Mechanics in Marine Mammals

    DTIC Science & Technology

    2013-09-30

    Critical Care and Pain Medicine Beth Israel Deaconess Medical Center Boston, Massachusetts phone: 617-667-3092 email: sloring@bidmc.harvard.edu...well these data compare. We will then compare these data to our previous data from excised lungs collected at Woods Hole Oceanographic Institution

  7. [Benign myoepithelioma of the lung].

    PubMed

    El Mezni, F; Zeddini, A; Hamzaoui, A; Ismail, O; Ghrairi, H; Ben Miled, K; Smati, B; Kilani, T

    2004-11-01

    Benign myoepithelioma of the lung is a benign tumor caused by proliferating myoepithelial cells with no ductal component. These tumors are exceptional: only three cases have been reported in the literature. We report a fourth case in a 37-year-old woman at 8 months gestation. Pathological proof of diagnosis was obtained.

  8. Lung Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing lung cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  9. Carotenoids and lung cancer prevention

    USDA-ARS?s Scientific Manuscript database

    Understanding the molecular actions of carotenoids is critical for human studies involving carotenoids for prevention of lung cancer and cancers at other tissue sites. While the original hypothesis prompting the beta-carotene intervention trials was that beta-carotene exerts beneficial effects thro...

  10. RADIOAUTOGRAPHY OF CHOLESTEROL IN LUNG

    PubMed Central

    Darrah, Hilary K.; Hedley-Whyte, John; Hedley-Whyte, E. Tessa

    1971-01-01

    30 Swiss albino mice aged 8 days were injected intraperitoneally with 0.2 ml of a solution of 4% N,N-dimethyl-formamide in 5% dextrose in water containing cholesterol-1,2-3H (∼1 mCi/ml). Lung tissue was embedded in an Epon mixture after either acetone and propylene oxide dehydration, partial ethanol and Epon 812 dehydration, or the precipitation of cholesterol by digitonin succeeded by partial dehydration. The distribution of cholesterol-1,2-3H in lung parenchyma in 1µ Epon section radioautograms was compared with that in frozen section radioautograms and was found to be independent of the manner of tissue processing. Grain distribution in the tissue was essentially the same whether 16, 63, 93, or 100% radioactivity was retained in the lung. However, grain distribution in the alveolar spaces differed, presumably due to displacement of pulmonary surfactant, which contains cholesterol. Intracellular distribution of cholesterol, in electron microscope radioautograms, was the same with either 51% or 93% retention of radioactivity in the lung. Loss of radioactivity into the various processing solutions was monitored. The various processing techniques have different drawbacks. PMID:19866763

  11. Lung function in sisal ropemakers.

    PubMed Central

    Baker, M D; Irwig, L M; Johnston, J R; Turner, D M; Bezuidenhout, B N

    1979-01-01

    Lung function was measured by spirometry in 66 workers in a sisal ropemaking factory, and in their matched controls. The major atmospheric contaminant was the lubricant (or a component part thereof) used to soften the fibre. The concentration of airborne matter was generally less than 1 mug m--3. There was no difference in lung function between the two groups before the start of the working shift, that is, the mixture of softening lubricant and sisal caused no long-term effects. Although there was no change in lung function over the working shift in the group making sisal rope, the control group did show a significant increase in lung function over the same period. This suggests that an effect attributable to the lubricant and sisal dust did exist. In previous studies little mention has been made of the softeners used in the processing of sisal fibre. These additives may exert a significant effect on ventilatory capacity and may act in conjunction with sisal dust. PMID:500780

  12. Lung Ventilation/Perfusion Scan

    MedlinePlus

    ... Scan Lung VQ Scan Related Topics Arrhythmia Cough Deep Vein Thrombosis Pulmonary Embolism Send a link to NHLBI to someone by ... this topic. Related reading Chest X Ray Cough Deep Vein Thrombosis Pulmonary Embolism Rate This Content: Updated: December 9, 2016 Twitter ...

  13. [Lung infiltrations in Hodgkin lymphoma].

    PubMed

    Ciurea-Löchel, A; Ciurea, A; Stey, C; Pestalozzi, B

    2001-08-02

    We report the case of a young patient presenting with cervical lymphadenopathy and interstitial pulmonary infiltrates due to Hodgkin's Disease. Although lung involvement regressed under chemotherapy, we observed new alveolar infiltrates during treatment. Steroid administration after exclusion of an infectious cause was followed by rapid clinical and radiological improvement, indicating the probable presence of pulmonary bleomycine toxicity.

  14. Lung Cancer Staging and Prognosis.

    PubMed

    Woodard, Gavitt A; Jones, Kirk D; Jablons, David M

    The seventh edition of the non-small cell lung cancer (NSCLC) TNM staging system was developed by the International Association for the Staging of Lung Cancer (IASLC) Lung Cancer Staging Project by a coordinated international effort to develop data-derived TNM classifications with significant survival differences. Based on these TNM groupings, current 5-year survival estimates in NSLCC range from 73 % in stage IA disease to 13 % in stage IV disease. TNM stage remains the most important prognostic factor in predicting recurrence rates and survival times, followed by tumor histologic grade, and patient sex, age, and performance status. Molecular prognostication in lung cancer is an exploding area of research where interest has moved beyond TNM stage and into individualized genetic tumor analysis with immunohistochemistry, microarray, and mutation profiles. However, despite intense research efforts and countless publications, no molecular prognostic marker has been adopted into clinical use since most fail in subsequent cross-validation with few exceptions. The recent interest in immunotherapy for NSCLC has identified new biomarkers with early evidence that suggests that PD-L1 is a predictive marker of a good response to new immunotherapy drugs but a poor prognostic indicator of overall survival. Future prognostication of outcomes in NSCLC will likely be based on a combination of TNM stage and molecular tumor profiling and yield more precise, individualized survival estimates and treatment algorithms.

  15. Lung cancer tissue diagnosis in poor lung function: addressing the ongoing percutaneous lung biopsy FEV1 paradox using Heimlich valve.

    PubMed

    Abdullah, R; Tavare, A N; Creamer, A; Creer, D; Vancheeswaran, R; Hare, S S

    2016-08-01

    Many centres continue to decline percutaneous lung biopsy (PLB) in patients with poor lung function (particularly FEV1 <1 L) due to the theoretically increased risk of pneumothorax. This practice limits access to novel lung cancer therapies and minimally invasive surgical techniques. Our retrospective single-centre analysis of 212 patients undergoing PLB, all performed prospectively and blinded to lung function, demonstrates that using ambulatory Heimlich valve chest drain (HVCD) to treat significant postbiopsy pneumothorax facilitates safe, diagnostic, early discharge lung biopsy irrespective of lung function with neither FEV1 <1 L nor transfer coefficient for carbon monoxide (TLCO) <40% predicted shown to be independent predictors of HVCD insertion or pneumothorax outcomes. Incorporating ambulatory HVCD into standard PLB practice thereby elegantly bridges the gap that currently exists between tissue diagnosis in patients with poor lung function and the advanced therapeutic options available for this cohort.

  16. High-frequency oscillation combined with arteriovenous extracorporeal lung assist reduces lung injury.

    PubMed

    Muellenbach, Ralf M; Kredel, Markus; Wilhelm, Jochen; Küstermann, Julian; Fink, Ludger; Siebenlist, Gregor; Siebenliest, Gregor; Klosterhalfen, Bernd; Foerster, Carola Y; Kranke, Peter; Wunder, Christian; Roewer, Norbert; Brederlau, Jörg

    2010-04-01

    In order to optimize the lung-protective potential of high-frequency oscillatory ventilation (HFOV), it is currently recommended to maximize oscillatory frequencies. However, very high frequencies may lead to insufficient CO(2) elimination with severe respiratory acidosis. Arteriovenous extracorporeal lung assist (av-ECLA) allows near total CO(2) removal, thereby allowing for maximization of the lung-protective potential of HFOV. The aim of this study was to determine the impact of HFOV and av-ECLA on lung inflammation and function compared to conventional lung-protective ventilation. In a porcine surfactant depletion model of lung injury, the authors randomly assigned 16 female pigs to conventional lung-protective ventilation and HFOV/ECLA. Both strategies were combined with an "open-lung" approach. Gas exchange and hemodynamic parameters were measured at intervals during the 24-hour study period. Postmortem, lung tissue was analyzed to determine histological damage and lung inflammation. The authors found that the combination of HFOV and av-ECLA (1) allows significant reductions in mean and peak airway pressures; and (2) reduces histological signs of lung inflammation in the basal regions of the lung. HFOV/av-ECLA reduces histological signs of lung inflammation compared to conventional lung-protective ventilation strategies. Thus, combination of HFOV and av-ECLA might be a further lung-protective tool if conventional ventilation strategies are failing.

  17. TACE in perinatal mouse lung epithelial cells promotes lung saccular formation

    PubMed Central

    Xu, Wei; Liu, Chengyu; Kaartinen, Vesa; Chen, Hui; Lu, Chi-Han; Zhang, Wenming; Luo, Yongfeng

    2013-01-01

    Tumor necrosis factor-α converting enzyme (TACE) is a cell membrane sheddase, expressed in both developmental lung epithelia and mesenchyme. Global abrogation of TACE results in neonatal lethality and multiple organ developmental abnormalities, including dysplastic lung. To further define the roles of TACE in regulating lung development, lung epithelial and/or mesenchymal specific TACE conditional knockout mice were generated. Blockade of TACE function in developing lung epithelial cells caused reduced saccular formation, decreased cell proliferation, and reduced mid-distal lung epithelial cell differentiation. In contrast, mesenchymal TACE knockout did not have any phenotypic change in developing lung. Simultaneous abrogation of TACE in both lung epithelial and mesenchymal cells did not result in a more severe lung abnormality. Interestingly, these lung-specific TACE conditional knockout mice were not neonatal lethal, and their lung structures were essentially normal after alveolarization. In addition, TACE conditional knockout in developing cardiomyocytes resulted in noncompaction of ventricular myocardium, as seen in TACE conventional knockout mice. However, these mice were also not neonatal lethal. In conclusion, lung epithelial TACE is essential for promoting fetal lung saccular formation, but not postnatal lung alveolarization in mice. Because the developmental abnormality of either lung or heart induced by TACE deficiency does not directly lead to neonatal lethality, the neonatal death of TACE conventional knockout mice is likely a result of synergistic effects of multiple organ abnormalities. PMID:24142516

  18. Predisposition for disrepair in the aged lung.

    PubMed

    Sueblinvong, Viranuj; Neujahr, David C; Mills, S Todd; Roser-Page, Susanne; Ritzenthaler, Jeffrey D; Guidot, David; Rojas, Mauricio; Roman, Jesse

    2012-07-01

    Idiopathic pulmonary fibrosis (IPF) is a devastating progressive lung disease with an average survival of only 3 to 5 years. The mechanisms underlying the initiation and progression of IPF are poorly understood, and treatments available have only modest effect on disease progression. Interestingly, the incidence of IPF is approximately 60 times more common in individuals aged 75 years and older, but the mechanism by which aging promotes fibrosis is unclear. The authors hypothesized that aged lungs have a profibrotic phenotype that render it susceptible to disrepair after injury. Young and old mice were treated with bleomycin to examine disrepair in the aged lung. In addition, uninjured young and old mouse lungs were analyzed for transforming growth factor-beta 1 (TGF-β1) production, extracellular matrix composition and lung fibroblast phenotype. Lung fibroblasts were treated with a DNA methyltransferase inhibitor to examine the potential epigenetic mechanisms involved in age-associated phenotypic alterations. The lungs of old mice showed worse fibrosis after bleomycin-induced injury compared with the lungs from young mice. At baseline, aged lungs expressed a profibrotic phenotype characterized by increased mRNA expression for fibronectin extracellular domain A (Fn-EDA) and the matrix metalloproteinases (MMPs) MMP-2 and MMP-9. Old lungs also expressed higher levels of TGF-β receptor 1 and TGF-β1 mRNA, protein and activity as determined by increased Smad3 expression, protein phosphorylation and DNA binding. Lung fibroblasts harvested from aged lungs showed reduced expression of the surface molecule Thy-1, a finding also implicated in lung fibrosis; the latter did not seem related to Thy-1 gene methylation. Altogether, aged lungs manifest a profibrotic phenotype characterized by enhanced fibronectin extracellular domain A and MMP expression and increased TGF-β1 expression and signaling and are populated by Thy-1-negative fibroblasts, all implicated in the

  19. Electrochemical treatment of lung cancer

    SciTech Connect

    Xin, Y.L.; Xue, F.Z.; Ge, B.S.; Zhao, F.R.; Shi, B.; Zhang, W.

    1997-03-01

    A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter. The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.

  20. Lung function in insulation workers.

    PubMed Central

    Clausen, J; Netterstrøm, B; Wolff, C

    1993-01-01

    To evaluate the effects of working with modern insulation materials (rock and glass wool), the members of the Copenhagen Union of Insulation Workers were invited to participate in a study based on a health examination that included lung function tests. Three hundred and forty men (74%) agreed to participate, and 166 bus drivers served as the control group. Age distribution, height, and smoking habits were similar in the two groups. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were used as tests for lung function. There were no differences in FVC between the study and control groups, but the insulation workers had significantly lower values of FEV1 (mean 2.51) compared with the controls (mean 3.4 1), independent of smoking habits. Six years before the present study, 114 of the insulation workers participated in a similar study, and eight years after the initial study, the lung function of 59 of the bus drivers was tested. The decline in FVC in insulation workers who smoked was significantly higher (7.7 cl/year) than in bus drivers who smoked (3.1 cl/year); the decline in FEV1 was significantly higher in insulation workers independent of smoking habits (17.0 cl/year v 2.9 cl/year). Self assessed former exposure to asbestos was not associated with lung function in insulation workers. The study concludes that working with modern insulation materials is associated with increased risk of developing obstructive lung disease. PMID:8457492