2014-01-01
Background Acute interstitial pneumonia is a rare interstitial lung disease that rapidly progresses to respiratory failure or death. Several studies showed that myofibroblast plays an important role in the evolution of diffuse alveolar damage, which is the typical feature of acute interstitial pneumonia. However, no evidence exists whether alveolar epithelial cells are an additional source of myofibroblasts via epithelial-mesenchymal transition in acute interstitial pneumonia. Case presentation In this report, we present a case of acute interstitial pneumonia in a previously healthy 28-year-old non-smoking woman. Chest high-resolution computed tomography scan showed bilateral and diffusely ground-glass opacification. The biopsy was performed on the fifth day of her hospitalization, and results showed manifestation of acute exudative phase of diffuse alveolar damage characterized by hyaline membrane formation. On the basis of the preliminary diagnosis of acute interstitial pneumonia, high-dose glucocorticoid was used. However, this drug showed poor clinical response and could improve the patient’s symptoms only during the early phase. The patient eventually died of respiratory dysfunction. Histological findings in autopsy were consistent with the late form of acute interstitial pneumonia. Conclusions The results in this study revealed that alveolar epithelial cells underwent epithelial-mesenchymal transition and may be an important origin of myofibroblasts in the progression of acute interstitial pneumonia. Conducting research on the transformation of alveolar epithelial cells into myofibroblasts in the lung tissue of patients with acute interstitial pneumonia may be beneficial for the treatment of this disease. However, to our knowledge, no research has been conducted on this topic. PMID:24755111
dos Santos, G.C.; Parra, E.R.; Stegun, F.W.; Cirqueira, C.S.; Capelozzi, V.L.
2013-01-01
Idiopathic interstitial pneumonias include complex diseases that have a strong interaction between genetic makeup and environmental factors. However, in many cases, no infectious agent can be demonstrated, and these clinical diseases rapidly progress to death. Theoretically, idiopathic interstitial pneumonias could be caused by the Epstein-Barr virus, cytomegalovirus, adenovirus, hepatitis C virus, respiratory syncytial virus, and herpesvirus, which may be present in such small amounts or such configuration that routine histopathological analysis or viral culture techniques cannot detect them. To test the hypothesis that immunohistochemistry provides more accurate results than the mere histological demonstration of viral inclusions, this method was applied to 37 open lung biopsies obtained from patients with idiopathic interstitial pneumonias. As a result, immunohistochemistry detected measles virus and cytomegalovirus in diffuse alveolar damage-related histological patterns of acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia in 38 and 10% of the cases, respectively. Alveolar epithelium infection by cytomegalovirus was observed in 25% of organizing pneumonia patterns. These findings were coincident with nuclear cytopathic effects but without demonstration of cytomegalovirus inclusions. These data indicate that diffuse alveolar damage-related cytomegalovirus or measles virus infections enhance lung injury, and a direct involvement of these viruses in diffuse alveolar damage-related histological patterns is likely. Immunohistochemistry was more sensitive than the histological demonstration of cytomegalovirus or measles virus inclusions. We concluded that all patients with diffuse alveolar damage-related histological patterns should be investigated for cytomegalovirus and measles virus using sensitive immunohistochemistry in conjunction with routine procedures. PMID:24270907
Diffuse Alveolar Damage: A Common Phenomenon in Progressive Interstitial Lung Disorders
Kaarteenaho, Riitta; Kinnula, Vuokko L.
2011-01-01
It has become obvious that several interstitial lung diseases, and even viral lung infections, can progress rapidly, and exhibit similar features in their lung morphology. The final histopathological feature, common in these lung disorders, is diffuse alveolar damage (DAD). The histopathology of DAD is considered to represent end stage phenomenon in acutely behaving interstitial pneumonias, such as acute interstitial pneumonia (AIP) and acute exacerbations of idiopathic pulmonary fibrosis (IPF). Acute worsening and DAD may occur also in patients with nonspecific interstitial pneumonias (NSIPs), and even in severe viral lung infections where there is DAD histopathology in the lung. A better understanding of the mechanisms underlying the DAD reaction is needed to clarify the treatment for these serious lung diseases. There is an urgent need for international efforts for studying DAD-associated lung diseases, since the prognosis of these patients has been and is still dismal. PMID:21637367
Desquamative interstitial pneumonia associated with chrysotile asbestos fibres.
Freed, J A; Miller, A; Gordon, R E; Fischbein, A; Kleinerman, J; Langer, A M
1991-01-01
The drywall construction trade has in the past been associated with exposure to airborne asbestos fibres. This paper reports a drywall construction worker with 32 years of dust exposure who developed dyspnoea and diminished diffusing capacity, and showed diffuse irregular opacities on chest radiography. He did not respond to treatment with corticosteroids. Open lung biopsy examination showed desquamative interstitial pneumonia. Only a single ferruginous body was seen on frozen section, but tissue examination by electron microscopy showed an extraordinary pulmonary burden of mineral dust with especially high concentrations of chrysotile asbestos fibres. This report emphasises the need to consider asbestos fibre as an agent in the aetiology of desquamative interstitial pneumonia. The coexistent slight interstitial fibrosis present in this case is also considered to have resulted from exposure to mineral dust, particularly ultramicroscopic asbestos fibres. Images PMID:1645584
Hwang, Jeong-Hwa; Misumi, Shigeki; Sahin, Hakan; Brown, Kevin K; Newell, John D; Lynch, David A
2009-01-01
To compare the computed tomographic (CT) features of idiopathic fibrosing interstitial pneumonia with those of pulmonary fibrosis related to collagen vascular disease (CVD). We reviewed the CT scans of 177 patients with diffuse interstitial pulmonary fibrosis, of which 97 had idiopathic fibrosing interstitial pneumonia and 80 had CVD. The CT images were systematically scored for the presence and extent of pulmonary and extrapulmonary abnormalities. Computed tomographic diagnosis of usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was assigned. A CT pattern of UIP was identified in 59 (60.8%) of patients with idiopathic fibrosing interstitial pneumonia compared with 15 (18.7%) of those patients with CVD; conversely, the CT diagnosis of NSIP was made in 51 (64%) of patients with CVD compared with 36 (37%) of patients with idiopathic disease (P < 0.01). In 113 patients who had lung biopsy, the CT diagnoses of UIP and NSIP were concordant with the histologic diagnoses in 36 of 50 patients and 34 of 41 patients, respectively. Pleural effusions, esophageal dilation, and pericardial abnormalities were more frequent in patients with CVD than in patients with idiopathic fibrosing interstitial pneumonia. Compared with patients with CVD, those patients with an idiopathic fibrosing interstitial pneumonia showed a higher prevalence of a UIP pattern and lower prevalence of an NSIP pattern as determined by CT. Identification of coexisting extrapulmonary abnormalities on CT can support a diagnosis of CVD.
Sekimoto, Yasuhito; Kato, Motoyasu; Shukuya, Takehiko; Koyama, Ryo; Nagaoka, Tetsutaro; Takahashi, Kazuhisa
2016-04-01
Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor receptor and a key drug for advanced non-small cell lung cancer. There are few reports describing bevacizumab-induced chronic interstitial pneumonia. A 62-year-old man with advanced non-small cell lung cancer was admitted to our hospital with dyspnea. He previously received four courses of carboplatin plus paclitaxel with bevacizumab combination therapy and thereafter received four courses of maintenance bevacizumab monotherapy. A chest-computed tomography scan on admission revealed diffuse ground glass opacity. He had not received any other drugs and did not have pneumonia. Thus, he was diagnosed with bevacizumab-induced chronic interstitial pneumonia and was treated with a high dose of corticosteroids. After steroid treatment, his dyspnea and radiological findings improved. This case report is the first description of bevacizumab-induced chronic interstitial pneumonia during maintenance therapy in a patient with non-small cell lung cancer.
Jelic, Tomislav M; Estalilla, Oscar C; Sawyer-Kaplan, Phyllis R; Plata, Milton J; Powers, Jeremy T; Emmett, Mary; Kuenstner, John T
2017-07-01
Diseases associated with coal mine dust continue to affect coal miners. Elucidation of initial pathological changes as a precursor of coal dust-related diffuse fibrosis and emphysema, may have a role in treatment and prevention. To identify the precursor of dust-related diffuse fibrosis and emphysema. Birefringent silica/silicate particles were counted by standard microscope under polarized light in the alveolar macrophages and fibrous tissue in 25 consecutive autopsy cases of complicated coal worker's pneumoconiosis and in 21 patients with tobacco-related respiratory bronchiolitis. Coal miners had 331 birefringent particles/high power field while smokers had 4 (p<0.001). Every coal miner had intra-alveolar macrophages with silica/silicate particles and interstitial fibrosis ranging from minimal to extreme. All coal miners, including those who never smoked, had emphysema. Fibrotic septa of centrilobular emphysema contained numerous silica/silicate particles while only a few were present in adjacent normal lung tissue. In coal miners who smoked, tobacco-associated interstitial fibrosis was replaced by fibrosis caused by silica/silicate particles. The presence of silica/silicate particles and anthracotic pigment-laden macrophages inside the alveoli with various degrees of interstitial fibrosis indicated a new disease: coal mine dust desquamative chronic interstitial pneumonia, a precursor of both dust-related diffuse fibrosis and emphysema. In studied coal miners, fibrosis caused by smoking is insignificant in comparison with fibrosis caused by silica/silicate particles. Counting birefringent particles in the macrophages from bronchioalveolar lavage may help detect coal mine dust desquamative chronic interstitial pneumonia, and may initiate early therapy and preventive measures.
Yokohori, Naoko; Sato, Akitoshi; Hasegawa, Mizue; Katsura, Hideki; Hiroshima, Kenzo; Takemura, Tamiko
2017-01-01
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus involved in the pathogenesis of adult T-cell leukemia (ATL) and HTVL-1-associated bronchioloalveolar disorder (HABA). The clinical and pathological findings of HABA have been characterized as either a diffuse panbronchiolitis (DPB) pattern or idiopathic interstitial pneumonia (IIP) pattern. Treatments for HABA include corticosteroids for the IIP pattern and erythromycin for the DPB pattern. We herein report a case of HABA-associated unclassifiable interstitial pneumonia that improved with combined therapy with pirfenidone and erythromycin. This is the first report on the effectiveness of combined therapy with pirfenidone and erythromycin for HABA. PMID:28050003
Mukhopadhyay, Sanjay; Parambil, Joseph G
2012-10-01
Acute interstitial pneumonia (AIP) is a term used for an idiopathic form of acute lung injury characterized clinically by acute respiratory failure with bilateral lung infiltrates and histologically by diffuse alveolar damage (DAD), a combination of findings previously known as the Hamman-Rich syndrome. This review aims to clarify the diagnostic criteria of AIP, its relationship with DAD and acute respiratory distress syndrome (ARDS), key etiologies that need to be excluded before making the diagnosis, and the salient clinical features. Cases that meet clinical and pathologic criteria for AIP overlap substantially with those that fulfill clinical criteria for ARDS. The main differences between AIP and ARDS are that AIP requires a histologic diagnosis of DAD and exclusion of known etiologies. AIP should also be distinguished from "acute exacerbation of IPF," a condition in which acute lung injury (usually DAD) supervenes on underlying usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF). Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
020. Coexistence of lung adenocarcinoma and usual interstitial pneumonia: a case report
Baliaka, Aggeliki; Papaemmanouil, Styliani; Spyratos, Dionysis; Zarogoulidis, Paul; Sakkas, Leonidas
2015-01-01
Background Usual interstitial pneumonia (UIP)/idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia of unknown cause. The most common symptoms are progressively increased shortness of breath and dry cough. Some studies suggest an association between usual interstitial pneumonia and lung cancer through different pathogenetic mechanisms. Objective The case presentation of a patient with lung adenocarcinoma and UIP. Methods A 66-year-old male presented with persistent dry cough, hemoptysis and dyspnea. The chest radiographs revealed a mass in the lower lobe of the left lung, measuring 3 cm, as well as diffuse interstitial changes in the same lobe. Two partial lobectomies were performed. Results Histological examination of the mass showed moderately differentiated adenocarcinoma, focally with bronchoalveolar pattern (Immunohistochemical detection of EGFR: positive). The rest lung parenchyma presented histological appearance of UIP. Conclusions According to clinicopathological studies, the prevalence of lung cancer among patients with UIP/IPF varies between 4% and 9%. The overall median survival of IPF-Ca patients is seven months in comparison with IPF only patients (14 months).
Pierce, Elizabeth M.; Carpenter, Kristin; Jakubzick, Claudia; Kunkel, Steven L.; Flaherty, Kevin R.; Martinez, Fernando J.; Hogaboam, Cory M.
2007-01-01
Idiopathic interstitial pneumonias (IIPs) are a collection of pulmonary fibrotic diseases of unknown etiopathogenesis. CC chemokine receptor 7 (CCR7) is expressed in IIP biopsies and primary fibroblast lines, but its role in pulmonary fibrosis was not previously examined. To study the in vivo role of CCR7 in a novel model of pulmonary fibrosis, 1.0 × 106 primary fibroblasts grown from idiopathic pulmonary fibrosis/usual interstitial pneumonia, nonspecific interstitial pneumonia, or histologically normal biopsies were injected intravenously into C.B-17 severe combined immunodeficiency (SCID)/beige (bg) mice. At days 35 and 63 after idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblast injection, patchy interstitial fibrosis and increased hydroxyproline were present in the lungs of immunodeficient mice. Adoptively transferred nonspecific interstitial pneumonia fibroblasts caused a more diffuse interstitial fibrosis and increased hydroxyproline levels at both times, but injected normal human fibroblasts did not induce interstitial remodeling changes in C.B-17SCID/bg mice. Systemic therapeutic immunoneutralization of either human CCR7 or CC ligand 21, its ligand, significantly attenuated the pulmonary fibrosis in groups of C.B-17SCID/bg mice that received either type of IIP fibroblasts. Thus, the present study demonstrates that pulmonary fibrosis is initiated by the intravenous introduction of primary human fibroblast lines into immunodeficient mice, and this fibrotic response is dependent on the interaction between CC ligand 21 and CCR7. PMID:17392156
Agut, Amalia; Talavera, Jesus; Buendia, Antonio; Anson, Agustina; Santarelli, Giorgia; Gomez, Serafin
2015-01-01
A 1.5-year-old, 23 kg intact male Dalmatian dog was evaluated for acute respiratory insufficiency without a previous history of trauma or toxic exposition. Imaging revealed pneumomediastinum, pneumothorax, diffuse unstructured interstitial pulmonary pattern, pulmonary interstitial emphysema, and pneumoretroperitoneum. Histopathological evaluation of the lungs revealed perivascular and peribronchial emphysema, mild lymphocytic interstitial pneumonia with atypical proliferation of type II pneumocytes in bronchioles and alveoli. A lung disease resembling fibrosing interstitial pneumonia in man and cats has been previously reported in Dalmatians and should be included as a differential diagnosis for Dalmatians with this combination of clinical and imaging characteristics. © 2014 American College of Veterinary Radiology.
Ichikado, Kazuya
2014-02-01
Diffuse alveolar damage (DAD) is the pathologic feature of rapidly progressive lung diseases, including acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. The clinical significance and limitation of high-resolution computed tomography (HRCT) findings in these diseases were reviewed. The HRCT findings correlate well with pathologic phases (exudative, proliferative, and fibrotic) of DAD, although it cannot detect early exudative phase. Traction bronchiolectasis or bronchiectasis within areas of increased attenuation on HRCT scan is a sign of progression from the exudative to the proliferative and fibrotic phase of DAD. Extensive abnormalities seen on HRCT scans, which are indicative of fibroproliferative changes, were independently predictive of poor prognosis in patients with clinically early acute respiratory distress syndrome, acute interstitial pneumonia, and acute exacerbation of idiopathic pulmonary fibrosis. © 2013 Published by Elsevier Inc.
Plasek, Jiri; Dvorackova, Jana; Jahoda, Jan; Trulikova, Kristina; Mokosova, Radka; Danek, Tomas; Hrabovsky, Vladimir; Martinek, Arnost
2011-12-01
Acute interstitial pneumonia is characterized by rapid progressive dyspnoea degenerating into respiratory failure requiring mechanical ventilation. Acute interstitial pneumonia (AIP) and idiopathic pulmonary fibrosis (IPF) are separate clinic/pathological entities although overlap may be present. It is well-known that patients with IPF have increased risk of lung carcinoma; Adenocarcinoma in connection with IPF is less common. Moreover the subtype of adenocarcinoma, diffuse bronchoalveolar carcinoma has not yet been described. We report the case of 45 yr old former hockey player with increased bilateral reticular shadowing on chest radiograph, dyspnoea, velcro-like crackles, restrictive respiratory disease and mixed high-resolution computed tomography finding. During brief in-patient treatment the patient developed acute respiratory failure accompanied by multiorgan failure and disseminated coagulopathy. Deterioration of the microcirculation was followed by loss of peripheral vascular resistance, which was irreversible even with normalization of the blood gases achieved by extracorporeal membrane oxygenation. At autopsy, bronchoalveolar carcinoma in usual interstitial pneumonia (UIP) combined with areas of alveolar damage with hyaline membranes was found. This case alerts clinicians to unusual idiopathic pulmonary fibrosis manifestations and its complications. Close collaboration between clinicians, pathologists and laboratory physicians is highly recommended for early diagnosis and appropriate treatment.
Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT
2018-06-08
Pulmonary Arterial Hypertension; Pulmonary Hypertension; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Idiopathic Pulmonary Fibrosis; Sarcoidosis; Respiratory Bronchiolitis Associated Interstitial Lung Disease; Desquamative Interstitial Pneumonia; Cryptogenic Organizing Pneumonia; Acute Interstitial Pneumonitis; Idiopathic Lymphoid Interstitial Pneumonia; Idiopathic Pleuroparenchymal Fibroelastosis
Barisione, Giovanni; Brusasco, Claudia; Garlaschi, Alessandro; Baroffio, Michele; Brusasco, Vito
2016-05-01
Lung diffusing capacity for carbon monoxide (DLCO) is decreased in both usual interstitial pneumonia-idiopathic pulmonary fibrosis (UIP-IPF) and nonspecific interstitial pneumonia (NSIP), but is moderately related to computed tomography (CT)-determined fibrotic changes. This may be due to the relative insensitivity of DLCO to changes in alveolar membrane diffusive conductance (DMCO). The purpose of this study was to determine whether measurement of lung diffusing capacity for nitric oxide (DLNO) better reflects fibrotic changes than DLCO DLNO-DLCO were measured simultaneously in 30 patients with UIP-IPF and 30 with NSIP. Eighty-one matched healthy subjects served as a control group. The amount of pulmonary fibrosis was estimated by CT volumetric analysis of visually bounded areas showing reticular opacities and honeycombing. DMCO and pulmonary capillary volume (VC) were calculated. DLNO was below the lower limit of normal in all patients irrespective of extent and nature of disease, whereas DLCO was within the normal range in a nonnegligible number of patients. Both DLNO and DLCO were significantly correlated with visual assessment of fibrosis but DLNO more closely than DLCO DMCO was also below the lower limit of normal in all UIP-IPF and NSIP patients and significantly correlated with fibrosis extent in both diseases, whereas VC was weakly correlated with fibrosis in UIP-IPF and uncorrelated in NSIP, with normal values in half of patients. In conclusion, measurement of DLNO may provide a more sensitive evaluation of fibrotic changes than DLCO in either UIP-IPF or NSIP, because it better reflects DMCO. Copyright © 2016 the American Physiological Society.
Caminati, Antonella; Harari, Sergio
2005-12-01
Idiopathic interstitial pneumonias are a group of diffuse, inflammatory and fibrotic disorders of the lung parenchyma that cause restrictive physiology and impair gas exchange. Usual interstitial pneumonia and non-specific interstitial pneumonia comprise the majority of idiopathic interstitial pneumonia cases. Previous studies have identified the histopathologic pattern as the most important baseline factor in determining prognosis. The non-invasive diagnosis of these diseases is sometimes uncertain but histological evaluation is an imperfect gold-standard. In some cases, the biopsy specimen may not be representative of the entire lung. In other cases, there may be differences in interpretation of the histological findings. HRCT has also assumed a greater role in the diagnosis and management of patients with idiopathic interstitial pneumonia. Factors affecting prognosis are discussed controversially. Histological criteria, clinical features, or lung function parameters are not clear prognostic indicators. Increased interstitial abnormalities in the HRCT, parameters indicating restrictive lung function, desaturation at 6MWT and abnormal gas exchange are possible determinants of survival. The prognostic value of pulmonary function trends over time may prove more useful. Longitudinal behavior is a more accurate determinant of outcome than evaluation at a single point in time. It is important to remember that no predictor of survival can ever reliably predict an individual patient's prognosis. Physicians should realize this limitation, and use predictor tools as general prognostic guides, not crystal balls. However, due to the great variability in the natural history of the disease, close monitoring of the patients may be necessary to evaluate the individual course of each patient.
Cosgrove, Gregory P.; Janssen, William J.; Huie, Tristan J.; Burnham, Ellen L.; Heinz, David E.; Curran-Everett, Douglas; Sahin, Hakan; Schwarz, Marvin I.; Cool, Carlyne D.; Groshong, Steve D.; Geraci, Mark W.; Tuder, Rubin M.; Hyde, Dallas M.; Henson, Peter M.
2012-01-01
Background: Lymphangiogenesis responds to tissue injury as a key component of normal wound healing. The development of fibrosis in the idiopathic interstitial pneumonias may result from abnormal wound healing in response to injury. We hypothesize that increased lymphatic vessel (LV) length, a marker of lymphangiogenesis, is associated with parenchymal components of the fibroblast reticulum (organizing collagen, fibrotic collagen, and fibroblast foci), and its extent correlates with disease severity. Methods: We assessed stereologically the parenchymal structure of fibrotic lungs and its associated lymphatic network, which was highlighted immunohistochemically in age-matched samples of usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) with FVC < 80%, COPD with a Global Initiative for Obstructive Lung Disease stage 0, and normal control lungs. Results: LV length density, as opposed to vessel volume density, was found to be associated with organizing and fibrotic collagen density (P < .0001). Length density of LVs and the volume density of organizing and fibrotic collagen were significantly associated with severity of both % FVC (P < .001) and diffusing capacity of the lung for carbon monoxide (P < .001). Conclusions: Severity of disease in UIP and NSIP is associated with increased LV length and is strongly associated with components of the fibroblast reticulum, namely organizing and fibrotic collagen, which supports a pathogenic role of LVs in these two diseases. Furthermore, the absence of definable differences between UIP and NSIP suggests that LVs are a unifying mechanism for the development of fibrosis in these fibrotic lung diseases. PMID:22797508
Advances in the treatment of rheumatic interstitial lung disease.
Vassallo, Robert; Thomas, Charles F
2004-05-01
Interstitial lung disease frequently complicates the rheumatic diseases. The purpose of this review is to outline recent advances and current concepts regarding the management of these interstitial lung diseases. Several histologic lesions cause interstitial lung disease in rheumatic diseases, including nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, lymphocytic interstitial pneumonia, desquamative interstitial pneumonia, and acute interstitial pneumonia. Although the relative frequency of occurrence of these histopathologic lesions is not definitively established, it seems that nonspecific interstitial pneumonia accounts for a large proportion of rheumatic disease-associated interstitial lung diseases. Although usual interstitial pneumonia generally responds poorly to corticosteroid therapy, other forms of interstitial pneumonia are often steroid responsive and have a more favorable long-term prognosis. Pulmonary hypertension is increasingly recognized as a complication of these interstitial lung diseases. Treatment of pulmonary hypertension in these patients provides clinical benefit and may suppress pulmonary inflammation and fibrosis. Lung transplantation is a treatment option for selected patients with severe pulmonary involvement and limited life expectancy. Interstitial lung disease is common in the rheumatic diseases, may be caused by a variety of lesions that respond differently to treatment, and may lead to the development of pulmonary hypertension. Whether the prognosis of interstitial lung disease associated with rheumatic disease is similar to that associated with the idiopathic interstitial pneumonias is not known. Treatment of these interstitial lung diseases should take into account the specific histologic lesion, the activity of the underlying rheumatic disease, and associated pulmonary hypertension, if present. The diagnosis of a rheumatic disease is no longer an absolute contraindication to lung transplantation.
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Ohori, N.P.; Sciurba, F.C.; Owens, G.R.
We report four cases of giant-cell interstitial pneumonia that occurred in association with exposure to hard metals. All patients presented with chronic interstitial lung disease and had open-lung biopsies that revealed marked interstitial fibrosis, cellular interstitial infiltrates, and prominent intraalveolar macrophages as well as giant cells displaying cellular cannibalism. We also review the literature to determine the sensitivity and specificity of giant-cell interstitial pneumonia for hard-metal pneumoconiosis. Although hard-metal pneumoconiosis may take the form of usual interstitial pneumonia, desquamative interstitial pneumonia, and giant-cell interstitial pneumonia, the finding of giant-cell interstitial pneumonia is almost pathognomonic of hard-metal disease and should provokemore » an investigation of occupational exposure. 25 references.« less
Chylothorax in dermatomyositis complicated with interstitial pneumonia.
Isoda, Kentaro; Kiboshi, Takao; Shoda, Takeshi
2017-04-01
Chylothorax is a disease in which chyle leaks and accumulates in the thoracic cavity. Interstitial pneumonia and pneumomediastinum are common thoracic manifestations of dermatomyositis, but chylothorax complicated with dermatomyositis is not reported. We report a case of dermatomyositis with interstitial pneumonia complicated by chylothorax. A 77-year-old woman was diagnosed as dermatomyositis with Gottron's papules, skin ulcers, anti-MDA5 antibody and rapid progressive interstitial pneumonia. Treatment with betamethasone, tacrolimus and intravenous high-dose cyclophosphamide was initiated, and her skin symptoms and interstitial pneumonia improved once. However, right-sided chylothorax began to accumulate and gradually increase, and at the same time, her interstitial pneumonia began to exacerbate, and skin ulcers began to reappear on her fingers and auricles. Although her chylothorax improved by fasting and parenteral nutrition, she died due to further exacerbations of dermatomyositis and interstitial pneumonia in spite of steroid pulse therapy, increase in the betamethasone dosage, additional intravenous high-dose cyclophosphamide and plasma pheresis. An autopsy showed no lesions such as malignant tumors in the thoracic cavity. This is the first report of chylothorax complicated by dermatomyositis with interstitial pneumonia.
Pneumocyte injury and ubiquitin-positive pneumocytes in interstitial lung diseases*
Yamada, Tsutomu; Kawabata, Yoshinori
2015-01-01
Pneumocyte injury is a characteristic of pulmonary interstitial pneumonias (IPs). Histological markers of pneumocyte injury and inflammation include pneumocyte necrosis, erosion, hyaline membrane and fibrin exudation with subsequent intraluminal granulation tissue formation. We found that intracytoplasmic inclusions in pneumocytes are ubiquitin-positive (Ub+) and that the number of Ub+ pneumocytes shows positive correlation with the extent of diffuse alveolar damage (DAD). To determine the role of Ub+ pneumocytes and inclusions in IPs, we studied their relationship with pathological and clinical features of DAD, usual interstitial pneumonia (UIP) and organizing pneumonia (OP), including airspace enlargement with fibrosis (AEF). We analysed Ub+ pneumocytes, inclusions, erosions and intraluminal granulation tissue in relation to pneumocyte injury. The numbers of immunohistochemically identified Ub+ inclusions in each IP were higher than the number of inclusions detected by light microscopy. The inclusions detected by Ub+ immunostaining were identical to the inclusions observed by light microscopy. UIP and DAD had many Ub+ inclusions, while OP and AEF had fewer Ub+ inclusions. These results suggest that the extent of Ub+ inclusions reflects the severity of pneumocyte injury among IPs. Thus, Ub+ inclusions are a histological marker of pneumocyte injury that may be helpful in determining the severity and prognosis of IPs. PMID:25123224
Collins, Bridget F; Spiekerman, Charles F; Shaw, Megan A; Ho, Lawrence A; Hayes, Jennifer; Spada, Carolyn A; Stamato, Caroline M; Raghu, Ganesh
2017-07-01
Some patients with autoimmune characteristics and idiopathic interstitial pneumonia, particularly usual interstitial pneumonia (UIP), do not fit neatly into the category of connective tissue disease-associated interstitial lung disease (CTD-ILD), idiopathic pulmonary fibrosis (IPF), or recently proposed yet to be validated criteria for interstitial pneumonia with autoimmune features (IPAF). Outcomes of these patients are unknown. This was a retrospective single-center study. Analyses of variance compared differences in mean change in FVC and diffusion capacity (Dlco) over 1 year among 124 well-defined patients (20 patients with positive autoantibodies with or without symptoms of connective tissue disease [AI-ILD], 15 patients with IPAF, 36 patients with CTD-ILD, and 53 patients with IPF with negative CTD serologies [Lone-IPF]). Of the patients, 75% with AI-ILD, 33% with IPAF, and 33% with CTD-ILD had UIP. Initial FVC and Dlco were similarly moderately reduced across groups. Mean change in FVC over 12 months was as follows: -60 mL (IPAF), -110 mL (AI-ILD), -10 mL (CTD-ILD), and -90 mL (Lone-IPF) (P = .52). Mean change in Dlco was as follows: 2.39 mL/mm Hg/min (IPAF), -1.15 mL/mm Hg/min (AI-ILD), -0.27 mL/mm Hg/min (CTD-ILD), and -1.05 mL/mm Hg/min (Lone-IPF) (P < .001). By pattern of disease, the mean change in FVC was as follows: -140 mL (UIP), 10 mL (nonspecific interstitial pneumonia), and 12 mL (unclassifiable/other) (P = .001). No clinically significant differences in pulmonary function to distinguish between patients with AI-ILD, IPAF, CTD-ILD, and Lone-IPF were observed after 1 year. Longer periods of follow-up are needed to understand the outcomes of these patients. It is not yet clear whether AI-ILD is a distinct phenotype or a variant of the newly proposed entity IPAF. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Gharib, A M; Stern, E J
2001-11-01
Infection of the lower respiratory tract, acquired by way of the airways and confined to the lung parenchyma and airways, typically presents radiologically as one of three patterns: (1) focal nonsegmental or lobar pneumonia, (2) multifocal bronchopneumonia or lobular pneumonia, and (3) focal or diffuse "interstitial" pneumonia. These patterns can be useful in identifying the etiological organism in the appropriate clinical setting. To serve the purpose of this article, these patterns are used as the primary method of classification of pulmonary infections caused by different organisms. Mycobacterial and fungal pulmonary infections are reviewed separately because of their wide range of radiographic appearance that depend on the stage of the disease at presentation. This article discusses the clinical and radiographic features of the most common causes of pneumonia, primarily in the adult population of the United States.
Paulin, Francisco; Doyle, Tracy J; Fletcher, Elaine A; Ascherman, Dana P; Rosas, Ivan O
2015-01-01
The prevalence of clinically evident interstitial lung disease in patients with rheumatoid arthritis is approximately 10%. An additional 33% of undiagnosed patients have interstitial lung abnormalities that can be detected with high-resolution computed tomography. Rheumatoid arthritis-interstitial lung disease patients have three times the risk of death compared to those with rheumatoid arthritis occurring in the absence of interstitial lung disease, and the mortality related to interstitial lung disease is rising. Rheumatoid arthritis-interstitial lung disease is most commonly classified as the usual interstitial pneumonia pattern, overlapping mechanistically and phenotypically with idiopathic pulmonary fibrosis, but can occur in a non-usual interstitial pneumonia pattern, mainly nonspecific interstitial pneumonia. Based on this, we propose two possible pathways to explain the coexistence of rheumatoid arthritis and interstitial lung disease: (i) Rheumatoid arthritis-interstitial lung disease with a non-usual interstitial pneumonia pattern may come about when an immune response against citrullinated peptides taking place in another site (e.g. the joints) subsequently affects the lungs; (ii) Rheumatoid arthritis-interstitial lung disease with a usual interstitial pneumonia pattern may represent a disease process in which idiopathic pulmonary fibrosis-like pathology triggers an immune response against citrullinated proteins that promotes articular disease indicative of rheumatoid arthritis. More studies focused on elucidating the basic mechanisms leading to different sub-phenotypes of rheumatoid arthritis-interstitial lung disease and the overlap with idiopathic pulmonary fibrosis are necessary to improve our understanding of the disease process and to define new therapeutic targets.
Kuza, Catherine; Matheos, Theofilos; Kathman, Deirdre; Heard, Stephen O
2016-02-01
Acute fibrinous and organizing pneumonia (AFOP) is a rare histologic interstitial pneumonia pattern recently described in the literature with fewer than 120 cases published. AFOP is often difficult to diagnose and may be mistaken for other pulmonary disorders such as interstitial pneumonias or pneumonitides. Patients often present with vague symptoms of cough, dyspnea, hemoptysis, fatigue, and occasionally respiratory failure. Radiological findings show diffuse patchy opacities and ground glass appearance of the lungs. On histologic examination, intra-alveolar fibrin balls are observed. We discuss a case of a man who presented with hemoptysis and dyspnea and whose open lung biopsy revealed AFOP. We will describe the presentation, diagnosis, and post-discharge course, and review the current literature. There are only 4 cases which have reported the patients' course of disease after 1 year, the longest being 2 years. To our knowledge, this is the only case of AFOP in the literature that describes the course of a patient more than 2 years after the diagnosis of AFOP, and is the most comprehensive review of the current literature. Copyright © 2015 Elsevier Inc. All rights reserved.
The pulmonary histopathology of anti-KS transfer RNA synthetase syndrome.
Schneider, Frank; Aggarwal, Rohit; Bi, David; Gibson, Kevin; Oddis, Chester; Yousem, Samuel A
2015-01-01
The clinical spectrum of the antisynthetase syndromes (AS) has been poorly defined, although some frequently present with pulmonary manifestations. The anti-KS anti-asparaginyl-transfer RNA synthetase syndrome is one in which pulmonary interstitial lung disease is almost always present and yet the histopathologic spectrum is not well described. To define the morphologic manifestations of pulmonary disease in those patients with anti-KS antiasparaginyl syndrome. We reviewed the connective tissue disorder registry of the University of Pittsburgh and identified those patients with anti-KS autoantibodies who presented with interstitial lung disease and had surgical lung biopsies. The 5 patients with anti-KS antisynthetase syndrome were usually women presenting with dyspnea and without myositis, but with mechanic's hands (60%) and Raynaud phenomenon (40%). They most often presented with a usual interstitial pneumonia pattern of fibrosis (80%), with the final patient displaying organizing pneumonia. Pulmonary interstitial lung disease is a common presentation in patients with the anti-KS-antisynthetase syndrome, who are often women with rather subtle or subclinical connective tissue disease, whereas the literature emphasizes the nonspecific interstitial pneumonia pattern often diagnosed clinically. Usual interstitial pneumonia and organizing pneumonia patterns of interstitial injury need to be added to this clinical differential diagnosis.
Yagishita, Mizuki; Kondo, Yuya; Terasaki, Toshihiko; Terasaki, Mayu; Shimizu, Masaru; Honda, Fumika; Oyama, Ayako; Takahashi, Hiroyuki; Yokosawa, Masahiro; Asashima, Hiromitsu; Hagiwara, Shinya; Tsuboi, Hiroto; Matsumoto, Isao; Sumida, Takayuki
2018-02-28
Patients with clinically amyopathic dermatomyositis (CADM), a subset of dermatomyositis characterized by a lack of muscle involvement, frequently develop rapidly progressive and treatment-resistant interstitial lung disease. We report the case of a 49-year-old man who was diagnosed with CADM. He developed interstitial pneumonia, which did not respond to combination therapy with methylprednisolone pulse therapy, cyclophosphamide, and cyclosporine. We therefore attempted plasma exchange. After 7 courses of therapeutic plasma exchange, the interstitial pneumonia gradually improved. This case suggests that plasma exchange might be an effective therapeutic option for patients with progressive interstitial lung disease in steroid- and immunosuppressive therapy-refractive CADM.
Interstitial pneumonia and pulmonary hypertension associated with suspected ehrlichiosis in a dog.
Toom, Marjolein Lisette den; Dobak, Tetyda Paulina; Broens, Els Marion; Valtolina, Chiara
2016-07-07
In dogs with canine monocytic ehrlichiosis (CME), respiratory signs are uncommon and clinical and radiographic signs of interstitial pneumonia are poorly described. However, in human monocytic ehrlichiosis, respiratory signs are common and signs of interstitial pneumonia are well known. Pulmonary hypertension (PH) is classified based on the underlying disease and its treatment is aimed at reducing the clinical signs and, if possible, addressing the primary disease process. PH is often irreversible, but can be reversible if it is secondary to a treatable underlying etiology. CME is currently not generally recognized as one of the possible diseases leading to interstitial pneumonia and secondary PH in dogs. Only one case of PH associated with CME has been reported worldwide. A seven-year-old, male intact, mixed breed dog was presented with 2 weeks history of lethargy and dyspnea. The dog previously lived in the Cape Verdean islands. Physical examination showed signs of right-sided congestive heart failure and poor peripheral perfusion. Thoracic radiography showed moderate right-sided cardiomegaly with dilation of the main pulmonary artery and a mild diffuse interstitial lung pattern with peribronchial cuffing. Echocardiography showed severe pulmonary hypertension with an estimated pressure gradient of 136 mm Hg. On arterial blood gas analysis, severe hypoxemia was found and complete blood count revealed moderate regenerative anemia and severe thrombocytopenia. A severe gamma hyperglobulinemia was also documented. Serology for Ehrlichia canis was highly positive. Treatment with oxygen supplementation, a typed packed red blood cell transfusion and medical therapy with doxycycline, pimobendan and sildenafil was initiated and the dog improved clinically. Approximately 2 weeks later, there was complete resolution of all clinical signs and marked improvement of the PH. This report illustrates that CME might be associated with significant pulmonary disease and should be considered as a possible differential diagnosis in dogs presenting with dyspnea and secondary pulmonary hypertension, especially in dogs that have been in endemic areas. This is important because CME is a treatable disease and its secondary lung and cardiac manifestations may be completely reversible.
Bilateral pneumothorax, lung cavitations, and pleural empyema in a cocaine addict.
Solaini, Leonardo; Solini, Leonardo; Gourgiotis, Stavros; Salemis, Nikolaos S; Koukis, Ioannis
2008-12-01
A case of bilateral pneumothorax, lung cavitations, and pleural empyema in a cocaine user is described. The patient was treated by left tube thoracostomy and right lower lobectomy. The postoperative course was uneventful. Six months later, the patient remains asymptomatic. The pathology examination of the specimen revealed infected bronchiectasis, interstitial desquamative pneumonia, diffuse alveolar damage, subsegmental arterial thrombosis, and consequent areas of pulmonary infarction.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Keane, T.J.; Van Dyk, J.; Rider, W.D.
Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical settingmore » is described.« less
Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza
2014-01-01
To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.
[Lipoid pneumonia related to workplace exposure to paint].
Abad Fernández, A; de Miguel Díez, J; López Vime, R; Gómez Santos, D; Nájera Botello, L; Jara Chinarro, B
2003-03-01
A 49-year-old man with no known history of pulmonary disease was treated at our hospital after observation of an interstitial pattern on a chest film. The patient was a smoker and professional painter. Computed tomography of the chest showed a diffuse bilateral ground-glass pattern. The lung biopsy showed intra-alveolar lipid accumulation in the form of vacuoles of varying sizes surrounded by numerous focally multinucleated macrophages, establishing a definitive diagnosis of exogenous lipoid pneumonia. Given the patient's profession, he was recommended to avoid workplace exposure to paraffins and oily sprays. The clinical course was favorable after exposure was stopped, with improved lung function and symptoms.
Kang, E H; Lee, E B; Shin, K C; Im, C H; Chung, D H; Han, S K; Song, Y W
2005-10-01
To assess the prevalence, characteristics and prognostic factors of interstitial lung disease (ILD) in Korean patients with polymyositis (PM), dermatomyositis (DM) and amyopathic dermatomyositis (ADM). We reviewed the medical records of 72 consecutive PM and DM patients, including six patients with ADM, who were seen at the Rheumatology Clinic of Seoul National University Hospital between 1984 and 2003. Twenty-nine PM/DM patients (40.3%) developed ILD. Anti-Jo-1 antibody and arthralgia were associated with the presence of ILD (P = 0.022 and P = 0.041, respectively), whereas dysphagia was more frequently found in patients without ILD (P = 0.041). Lung biopsies revealed diffuse alveolar damage (DAD) (n = 2), usual interstitial pneumonia (UIP) with DAD (n = 2), UIP (n = 1), and non-specific interstitial pneumonia (n = 2). Of the 29 patients, 11 (37.9%) died. The mean survival time in ILD patients was significantly shorter than in those without ILD (13.8+/-1.8 vs 19.2+/-0.9 yr, P = 0.017). Poor survival in ILD patients was associated with a Hamman-Rich-like presentation (P = 0.0000), ADM features (P = 0.0001) and an initial forced vital capacity (FVC) < or =60% (P = 0.024). ILD was observed in 40.3% of Korean PM/DM patients and was associated with poor survival. A Hamman-Rich-like presentation, ADM features and an initial FVC < or =60% were associated with poor survival in ILD.
Epimorphin expression in interstitial pneumonia
Terasaki, Yasuhiro; Fukuda, Yuh; Suga, Moritaka; Ikeguchi, Naoki; Takeya, Motohiro
2005-01-01
Epimorphin modulates epithelial morphogenesis in embryonic mouse organs. We previously suggested that epimorphin contributes to repair of bleomycin-induced pulmonary fibrosis in mice via epithelium-mesenchyme interactions. To clarify the role of epimorphin in human lungs, we evaluated epimorphin expression and localization in normal lungs, lungs with nonspecific interstitial pneumonia (NSIP), and lungs with usual interstitial pneumonia (UIP); we also studied the effect of recombinant epimorphin on cultured human alveolar epithelial cells in vitro. Northern and Western blotting analyses revealed that epimorphin expression in NSIP samples were significantly higher than those in control lungs and lungs with UIP. Immunohistochemistry showed strong epimorphin expression in mesenchymal cells of early fibrotic lesions and localization of epimorphin protein on mesenchymal cells and extracellular matrix of early fibrotic lesions in the nonspecific interstitial pneumonia group. Double-labeled fluorescent images revealed expression of matrix metalloproteinase 2 in re-epithelialized cells overlying epimorphin-positive early fibrotic lesions. Immunohistochemistry and metalloproteinase activity assay demonstrated augmented expression of metalloproteinase induced by recombinant epimorphin in human alveolar epithelial cells. These findings suggest that epimorphin contributes to repair of pulmonary fibrosis in nonspecific interstitial pneumonia, perhaps partly by inducing expression of matrix metalloproteinase 2, which is an important proteolytic factor in lung remodeling. PMID:15651999
Arcadu, Antonella; Byrne, Suzanne C; Pirina, Pietro; Hartman, Thomas E; Bartholmai, Brian J; Moua, Teng
2017-08-01
Little is known about presenting 'inconsistent' or 'possible' usual interstitial pneumonia (UIP) computed tomography (CT) patterns advancing to 'consistent' UIP as disease progresses in idiopathic pulmonary fibrosis (IPF). We hypothesized that if 'consistent' UIP represented more advanced disease, such a pattern on presentation should also correlate with more severe pulmonary function test (PFT) abnormalities. Consecutive IPF patients (2005-2013) diagnosed by international criteria with baseline PFT and CT were included. Presenting CTs were assessed by three expert radiologists for consensus UIP pattern ('consistent', 'possible', and 'inconsistent'). Approximation of individual and combined interstitial abnormalities was also performed with correlation of interstitial abnormalities and UIP CT pattern made with PFT findings and survival. Three-hundred and fifty patients (70% male) were included with a mean age of 68.3 years. Mean percent predicted forced vital capacity (FVC%) and diffusion capacity (DLCO%) was 64% and 45.5% respectively. Older age and male gender correlated more with 'consistent' UIP CT pattern. FVC% was not associated with any UIP pattern but did correlate with total volume of radiologist assessed interstitial abnormalities. DLCO% was lower in those with 'consistent' UIP pattern. A 'consistent' UIP CT pattern was also not independently predictive of survival after correction for age, gender, FVC%, and DLCO%. PFT findings appear to correlate with extent of radiologic disease but not specific morphologic patterns. Whether such UIP patterns represent different stages of disease severity or radiologic progression is not supported by coinciding pulmonary function decline. Copyright © 2017 Elsevier Ltd. All rights reserved.
[Lung is also involved in juvenile dermatomyositis].
Pouessel, G; Thumerelle, C; Nève, V; Santangelo, T; Flammarion, S; Pruvot, I; Tillie-Leblond, I; Deschildre, A
2014-07-01
Juvenile dermatomyositis is the leading cause of chronic idiopathic inflammatory myopathy of auto-immune origin in children. Lung involvement in inflammatory myopathies is well described in adults, involving mostly interstitial lung disease, aspiration pneumonia and alveolar hypoventilation. We propose to describe its specificities in children. Pulmonary involvement may be asymptomatic and therefore must be systematically screened for. In case of clinical or functional respiratory abnormality, a chest computed tomographic (CT) scan is necessary. In children, a decrease of respiratory muscle strength seems common and should be systematically and specifically searched for by non-invasive and reproducible tests (sniff test). Interstitial lung disease usually associates restrictive functional defect, impairment of carbon monoxide diffusion and interstitial lung disease on CT scan. As in adults, the first-line treatment of juvenile dermatomyositis is based on corticosteroids. Corticosteroid resistant forms require corticosteroid bolus or adjuvant immunosuppressive drugs (methotrexate or cyclosporine). There is no consensus in pediatrics for the treatment of diffuse interstitial lung disease. Complications of treatment, including prolonged steroid therapy, are frequent and therefore a careful assessment of the treatments risk-benefit ratio is necessary, especially in growing children. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.
Gonçalves-Venade, Gabriela; Lacerda-Príncipe, Nuno; Roncon-Albuquerque, Roberto; Paiva, José Artur
2018-05-01
Acute interstitial pneumonia (AIP) is a rare idiopathic interstitial lung disease with rapid progressive respiratory failure and high mortality. In the present report, three cases of AIP complicated by refractory respiratory failure supported with extracorporeal membrane oxygenation (ECMO) are presented. One male and two female patients (ages 27-59) were included. Venovenous ECMO support was provided using miniaturized systems, with two-site femoro-jugular circuit configuration. Despite lung protective ventilation, prone position and neuromuscular blockade, refractory respiratory failure of unknown etiology supervened (ratio of arterial oxygen partial pressure to fractional inspired oxygen 46-130) and ECMO was initiated after 3-7 days of mechanical ventilation. AIP diagnosis was established after exclusion of infectious and noninfectious acute respiratory distress syndrome on the basis of clinical and analytical data, bronchoalveolar lavage analysis and lung imaging, with a confirmatory surgical lung biopsy revealing diffuse alveolar damage of unknown etiology. Immunosuppressive treatment consisted in high-dose corticosteroids and cyclophosphamide in one case. Two patients survived to hospital discharge. ECMO allowed AIP diagnosis and treatment in the presence of refractory respiratory failure, therefore reducing ventilator-induced lung injury and bridging lung recovery in two patients. ECMO referral should be considered in refractory respiratory failure if AIP is suspected. © 2018 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
Glazer, Craig S
2015-03-01
Chronic hypersensitivity pneumonitis is increasingly recognized as an important mimic of other fibrotic lung diseases. This review will summarize recent data regarding the importance and difficulty of determining causative exposures both for accurate diagnosis and prognosis, and describe the expanded pathologic spectrum of the disease, the effects of fibrosis on prognosis and challenges in the diagnostic evaluation. Several recent publications show the potential pathologic patterns induced by chronic hypersensitivity pneumonitis are broader than the classic triad of bronchiolitis, interstitial infiltrates and granulomas. Other pathologic patterns include nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, bronchiolitis and airway centric fibrosis. Detecting a causative antigen in fibrotic hypersensitivity pneumonitis is challenging but critically important both for accurate diagnosis and improved prognosis. The prognosis in hypersensitivity pneumonitis worsens in the presence of fibrosis, but it remains significantly better than idiopathic pulmonary fibrosis. Hypersensitivity pneumonitis is increasingly recognized as an important cause of fibrotic interstitial lung disease. Hypersensitivity pneumonitis demonstrates a remarkable tendency to mimic other idiopathic interstitial pneumonias. A detailed exposure history remains a cornerstone of diagnosis and management.
Crackle analysis for chest auscultation and comparison with high-resolution CT findings.
Kawamura, Takeo; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Kido, Shoji; Jiang, Zhongwei; Matsunaga, Naofumi
2003-01-01
The purpose of our study was to clarify the correlation between respiratory sounds and the high-resolution CT (HRCT) findings of lung diseases. Respiratory sounds were recorded using a stethoscope in 41 patients with crackles. All had undergone inspiratory and expiratory CT. Subjects included 18 patients with interstitial pneumonia and 23 without interstitial pneumonia. Two parameters, two-cycle duration (2CD) and initial deflection width (IDW) of the "crackle," were induced by time-expanded waveform analysis. Two radiologists independently assessed 11 HRCT findings. An evaluation was carried out to determine whether there was a significant difference in the two parameters between the presence and absence of each HRCT finding. The two parameters of crackles were significantly shorter in the interstitial pneumonia group than the non-interstitial pneumonia group. Ground-glass opacity, honeycombing, lung volume reduction, traction bronchiectasis, centrilobular nodules, emphysematous change, and attenuation and volume change between inspiratory and expiratory CT were correlated with one or two parameters in all patients, whereas the other three findings were not. Among the interstitial pneumonia group, traction bronchiectasis, emphysematous change, and attenuation and volume change between inspiratory and expiratory CT were significantly correlated with one or two parameters. Abnormal respiratory sounds were correlated with some HRCT findings.
Park, Sang Ok; Seo, Joon Beom; Kim, Namkug; Lee, Young Kyung; Lee, Jeongjin; Kim, Dong Soon
2011-01-01
To evaluate the usefulness of an automated system for quantification and discrimination of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). An automated system to quantify six regional high-resolution CT (HRCT) patterns: normal, NL; ground-glass opacity, GGO; reticular opacity, RO; honeycombing, HC; emphysema, EMPH; and consolidation, CONS, was developed using texture and shape features. Fifty-four patients with pathologically proven UIP (n = 26) and pathologically proven NSIP (n = 28) were included as part of this study. Inter-observer agreement in measuring the extent of each HRCT pattern between the system and two thoracic radiologists were assessed in 26 randomly selected subsets using an interclass correlation coefficient (ICC). A linear regression analysis was used to assess the contribution of each disease pattern to the pulmonary function test parameters. The discriminating capacity of the system between UIP and NSIP was evaluated using a binomial logistic regression. The overall ICC showed acceptable agreement among the system and the two radiologists (r = 0.895 for the abnormal lung volume fraction, 0.706 for the fibrosis fraction, 0.895 for NL, 0.625 for GGO, 0.626 for RO, 0.893 for HC, 0.800 for EMPH, and 0.430 for CONS). The volumes of NL, GGO, RO, and EMPH contribute to forced expiratory volume during one second (FEV₁) (r = 0.72, β values, 0.84, 0.34, 0.34 and 0.24, respectively) and forced vital capacity (FVC) (r = 0.76, β values, 0.82, 0.28, 0.21 and 0.34, respectively). For diffusing capacity (DL(co)), the volumes of NL and HC were independent contributors in opposite directions (r = 0.65, β values, 0.64, -0.21, respectively). The automated system can help discriminate between UIP and NSIP with an accuracy of 82%. The automated quantification system of regional HRCT patterns can be useful in the assessment of disease severity and may provide reliable agreement with the radiologists' results. In addition, this system may be useful in differentiating between UIP and NSIP.
Hart, Samantha K; Waddell, Lori
2016-11-01
To describe a case of suspected drug-induced infiltrative lung disease (ILD) and acute respiratory failure associated with the administration of cytarabine and prednisone in a dog requiring mechanical ventilation. A 4.5-year-old, female spayed Yorkshire Terrier presented to the ICU with acute onset of respiratory distress following a 24-hour cytarabine infusion. The patient was previously diagnosed with meningoencephalitis of unknown etiology (MUO), caudal occipital malformation, and syringohydromyelia, and was being treated with oral prednisone and levetiracetam, and cytarabine infusions. The patient developed tachypnea and dyspnea, and had diffuse crackles on auscultation of all lung fields, and hypoxemia 6 hours following completion of the fourth cytarabine infusion (300 mg/m 2 ). Thoracic radiographs revealed diffuse, bilateral infiltrates consistent with noncardiogenic pulmonary edema or acute respiratory distress syndrome. Respiratory distress and hypoxemia persisted despite oxygen supplementation and furosemide therapy and led to initiation of mechanical ventilation. Approximately 12 hours later, the dog became progressively hypoxemic with worsening pulmonary edema. The owners elected euthanasia. Postmortem examination revealed pulmonary edema and diffuse interstitial pneumonia. Histopathologic evaluation revealed pulmonary edema, severe acute neutrophilic and histiocytic pneumonia, and multifocal interstitial fibrosis. Bacterial culture yielded no growth. Drug-induced ILD is rarely reported in the veterinary literature, and has not previously been reported in dogs receiving cytarabine. As with administration of any medication, adverse events may occur. While ILD is unlikely to be commonly recognized, it may be considered in veterinary patients receiving chemotherapy that acutely become dyspneic. © Veterinary Emergency and Critical Care Society 2016.
NASA Astrophysics Data System (ADS)
Yoshida, Mitsuhiro; Sakuma, Junko; Hayashi, Seiji; Abe, Kin'ya; Saito, Izumu; Harada, Shizuko; Sakatani, Mitsunoir; Yamamoto, Satoru; Matsumoto, Norinao; Kaneda, Yasufumi; Kishmoto, Tadamitsu
1995-10-01
Interstitial pneumonia is characterized by alveolitis with resulting fibrosis of the interstitium. To determine the relevance of humoral factors in the pathogenesis of interstitial pneumonia, we introduced expression vectors into Wistar rats via the trachea to locally overexpress humoral factors in the lungs. Human interleukin (IL) 6 and IL-6 receptor genes induced lymphocytic alveolitis without marked fibroblast proliferation. In contrast, overexpression of human transforming growth factor β1 or human platelet-derived growth factor B gene induced only mild or apparent cellular infiltration in the alveoli, respectively. However, both factors induced significant proliferation of fibroblasts and deposition of collagen fibrils. These histopathologic changes induced by the transforming growth factor β1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.
Itai, Junji; Ohshimo, Shinichiro; Kida, Yoshiko; Ota, Kohei; Iwasaki, Yasumasa; Hirohashi, Nobuyuki; Bonella, Francesco; Guzman, Josune; Costabel, Ulrich; Kohno, Nobuoki; Tanigawa, Koichi
2015-01-05
Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) might be beneficial for treating acute exacerbation (AE) of interstitial pneumonia (IP). Venovenous extracorporeal membranous oxygenation (VV-ECMO) is an emerging tool to avoid ventilator-induced lung injury. This is a report presenting the first three patients with AE of IP treated with a combined therapy of PMX-DHP and VV-ECMO. Patient 1 was a 68-year-old male with acute interstitial pneumonia, patient 2 a 67-year-old male with AE of idiopathic pulmonary fibrosis, and patient 3 a 61-year-old female with AE of collagen vascular disease-associated interstitial pneumonia. All patients were severely hypoxemic and required mechanical ventilation. A combined therapy using PMX-DHP and VV-ECMO was initiated with support of intravenous corticosteroids and antibiotics. Radiological findings, oxygenation and laboratory findings markedly improved and all patients survived without severe complications. A combined therapy of PMX-DHP and VV-ECMO might be a therapeutic option for AE of IP.
Pneumocystis Jiroveci Pneumonia
2008-10-01
patients with AIDS include CMV pneumonia, lymphocytic interstitial pneumonia, MAI infection, cryptococcal infection, Legionella , Mycoplasma...negative for Legionella , Streptococcus pneumoniae, and Cryptococcus neoformans. Pneumocystis direct fluorescent antibody (DFA) of the fluid was also
Acute Exacerbation in Interstitial Lung Disease
Leuschner, Gabriela; Behr, Jürgen
2017-01-01
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has been defined as an acute, clinically significant deterioration that develops within less than 1 month without obvious clinical cause like fluid overload, left heart failure, or pulmonary embolism. Pathophysiologically, damage of the alveoli is the predominant feature of AE-IPF which manifests histopathologically as diffuse alveolar damage and radiologically as diffuse, bilateral ground-glass opacification on high-resolution computed tomography. A growing body of literature now focuses on acute exacerbations of interstitial lung disease (AE-ILD) other than idiopathic pulmonary fibrosis. Based on a shared pathophysiology it is generally accepted that AE-ILD can affect all patients with interstitial lung disease (ILD) but apparently occurs more frequently in patients with an underlying usual interstitial pneumonia pattern. The etiology of AE-ILD is not fully understood, but there are distinct risk factors and triggers like infection, mechanical stress, and microaspiration. In general, AE-ILD has a poor prognosis and is associated with a high mortality within 6–12 months. Although there is a lack of evidence based data, in clinical practice, AE-ILD is often treated with a high dose corticosteroid therapy and antibiotics. This article aims to provide a summary of the clinical features, diagnosis, management, and prognosis of AE-ILD as well as an update on the current developments in the field. PMID:29109947
Acute pleurisy in sarcoidosis.
Gardiner, I T; Uff, J S
1978-01-01
A 47-year-old white man with sarcoidosis presented with a six-week history of acute painful pleurisy. On auscultation a loud pleural rub was heard at the left base together with bilateral basal crepitations. The chest radiograph showed hilar enlargement as well as diffuse lung shadowing. A lung biopsy showed the presence of numerous epithelioid and giant-cell granulomata, particularly subpleurally. A patchy interstitial pneumonia was also present. He was given a six-month course of prednisolone, and lung function returned to normal. Images PMID:644534
Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia
Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen Mª; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni
2016-01-01
Abstract Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables. We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: “presence” or “nonpresence” of bilateral Velcro crackles. Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern. In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care. PMID:26844464
Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia.
Sellarés, Jacobo; Hernández-González, Fernanda; Lucena, Carmen M; Paradela, Marina; Brito-Zerón, Pilar; Prieto-González, Sergio; Benegas, Mariana; Cuerpo, Sandra; Espinosa, Gerard; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni
2016-02-01
Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care.
[The clinicopathological features of acute fibrinous and organizing pneumonia].
Qiu, Yu-ying; Miao, Li-yun; Cai, Hou-rong; Xiao, Yong-long; Ye, Qing; Meng, Fan-qing; Feng, An-ning
2013-06-01
To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kantor, H.G.
In 1978, 89 patients were treated for (S. pneumoniae) pneumonia at New York Hospital-Cornell Medical Center. Only 40 cases met rather strict diagnostic criteria. Of these, 12 demonstrated the classical consolidative (air space) pattern usually ascribed to this disease. A bronchopneumonic (patch) pattern was demonstrated in an equal number of patients; interstitial (irregular linear) infiltrates were manifest in nine cases and a mixed interstitial and patchy presentation shown in seven cases. Absence of the consolidative pattern does not exclude pneumococcal pneumonia. Bacteriologic investigation is required to determine the proper diagnosis and course of therapy.
Severe interstitial pneumonia due to murine typhus in a patient returning from Bali.
Malheiro, Luís; Ceia, Filipa; Alves, João; Carvalho, Ana Cláudia; Sobrinho-Simões, Joana; Sousa, Rita; Sarmento, António; Santos, Lurdes
2017-01-01
Murine typhus has been increasingly reported as a cause of fever in returning travelers from Southeast Asia. We report a case of a previously healthy traveler returning from Bali with an non-specific febrile illness which quickly progressed to a severe form of interstitial pneumonia. After a careful epidemiological evaluation and laboratory analysis, murine typhus was diagnosed.
Histological evolution of pleuroparenchymal fibroelastosis
Hirota, Takako; Yoshida, Yuji; Kitasato, Yasuhiko; Yoshimi, Michihiro; Koga, Takaomi; Tsuruta, Nobuko; Minami, Masato; Harada, Taishi; Ishii, Hiroshi; Fujita, Masaki; Nabeshima, Kazuki; Nagata, Nobuhiko; Watanabe, Kentaro
2015-01-01
Aims To investigate the histological evolution in the development of pleuroparenchymal fibroelastosis (PPFE). Methods and results We examined four patients who had undergone surgical lung biopsy twice, or who had undergone surgical lung biopsy and had been autopsied, and in whom the histological diagnosis of the first biopsy was not PPFE, but the diagnosis of the second biopsy or of the autopsy was PPFE. The histological patterns of the first biopsy were cellular and fibrotic interstitial pneumonia, cellular interstitial pneumonia (CIP) with organizing pneumonia, CIP with granulomas and acute lung injury in cases 1, 2, 3, and 4, respectively. Septal elastosis was already present in the non-specific interstitial pneumonia-like histology of case 1, but a few additional years were necessary to reach consolidated subpleural fibroelastosis. In case 3, subpleural fibroelastosis was already present in the first biopsy, but only to a small extent. Twelve years later, it was replaced by a long band of fibroelastosis. The septal inflammation and fibrosis and airspace organization observed in the first biopsies were replaced by less cellular subpleural fibroelastosis within 3–12 years. Conclusions Interstitial inflammation or acute lung injury may be an initial step in the development of PPFE. PMID:25234959
Yamakawa, Hideaki; Hagiwara, Eri; Kitamura, Hideya; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Baba, Tomohisa; Iso, Shinichiro; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Kuwano, Kazuyoshi; Ogura, Takashi
2016-01-01
Background Patients with idiopathic interstitial pneumonias sometimes have a few features of connective tissue disease (CTD) and yet do not fulfil the diagnostic criteria for any specific CTD. Objective This study was conducted to elucidate the characteristics, prognosis, and disease behavior in patients with interstitial lung disease (ILD) associated with systemic sclerosis (SSc)-related autoantibodies. Methods We retrospectively analyzed medical records of 72 ILD patients: 40 patients with SSc (SSc-ILD) and 32 patients with SSc-related autoantibody-positive ILD but not with CTD (ScAb-ILD), indicating lung-dominant CTD with SSc-related autoantibody. Results Patients with SSc-ILD were predominantly females and non-smokers, and most had nonspecific interstitial pneumonia confirmed by high-resolution computed tomography (HRCT) and pathological analysis. However, about half of the patients with ScAb-ILD were male and current or ex-smokers. On HRCT analysis, honeycombing was more predominant in patients with ScAb-ILD than with SSc-ILD. Pathological analysis showed the severity of vascular intimal or medial thickening in the SSc-ILD patients to be significantly higher than that in the ScAb-ILD patients. Survival curves showed that the patients with ScAb-ILD had a significantly poorer outcome than those with SSc-ILD. Conclusion Data from this study suggest that lung-dominant CTD with SSc-related autoantibody is a different disease entity from SSc-ILD. PMID:27564852
Asato, Yuko; Kamitani, Toshiaki; Ootsuka, Kuniyuki; Kuramochi, Mizuki; Nakanishi, Kozo; Shimada, Tetsuya; Takahashi, Toshiyuki; Misu, Tatsuro; Aoki, Masashi; Fujihara, Kazuo; Kawabata, Yoshinori
2018-05-18
We herein report the case of a 76-year old man with aquaporin-4-Immunoglobulin-G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD), in whom transient interstitial pulmonary lesions developed at the early stage of the disease. Chest X-ray showed multiple infiltrative shadows in both upper lung fields, and computed tomography revealed abnormal shadows distributed randomly in the lungs. Surgical lung biopsy showed features of unclassifiable interstitial pneumonia, characterized by various types of air-space organization, which resulted in obscure lung structure. This is the first report to describe the pathological findings of interstitial pneumonia, which may represent a rare extra-central nervous system complication of NMOSD.
Kohashi, Yasuo; Arai, Toru; Sugimoto, Chikatoshi; Tachibana, Kazunobu; Akira, Masanori; Kitaichi, Masanori; Hayashi, Seiji; Inoue, Yoshikazu
2016-01-01
The prognosis of combined cases of pulmonary fibrosis and emphysema is unresolved partially because radiological differentiation between usual interstitial pneumonia and nonspecific interstitial pneumonia is difficult in coexisting emphysema cases. The purpose of this study was to clarify the clinical impact of emphysema on the survival of patients with idiopathic pulmonary fibrosis (IPF). One hundred and seven patients with interstitial lung diseases were diagnosed by surgical lung biopsies between 2006 and 2012, and 47 patients were diagnosed with IPF through multidisciplinary discussion. Emphysema on high-resolution computed tomography scans was evaluated semiquantitatively by visual scoring. Eight out of the 47 IPF patients showed a higher emphysema score (>3) and were diagnosed to have IPF-emphysema. The median survival time of patients with IPF-emphysema (1,734 days) from the initial diagnosis was significantly shorter than that of patients with IPF alone (2,229 days) by Kaplan-Meier analysis (p = 0.007, log-rank test). Univariate Cox proportional hazard regression analyses revealed that a higher total emphysema score (>3.0) was a significantly poor prognostic factor in addition to Krebs von den Lungen-6, surfactant protein-D, arterial oxygen tension, percent forced vital capacity, and percent diffusing capacity of carbon monoxide (%DLCO). Multivariate Cox proportional hazard regression analyses with the stepwise method showed that higher total emphysema score (>3) and %DLCO were significantly poor prognostic factors. The prognosis of IPF-emphysema was significantly worse than that of IPF alone. © 2016 S. Karger AG, Basel.
A case of pneumocystis pneumonia associated with everolimus therapy for renal cell carcinoma.
Saito, Yoshinobu; Nagayama, Mikie; Miura, Yukiko; Ogushi, Satoko; Suzuki, Yasutomo; Noro, Rintaro; Minegishi, Yuji; Kimura, Go; Kondo, Yukihiro; Gemma, Akihiko
2013-05-01
A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.
Diffusion and interactions of interstitials in hard-sphere interstitial solid solutions
NASA Astrophysics Data System (ADS)
van der Meer, Berend; Lathouwers, Emma; Smallenburg, Frank; Filion, Laura
2017-12-01
Using computer simulations, we study the dynamics and interactions of interstitial particles in hard-sphere interstitial solid solutions. We calculate the free-energy barriers associated with their diffusion for a range of size ratios and densities. By applying classical transition state theory to these free-energy barriers, we predict the diffusion coefficients, which we find to be in good agreement with diffusion coefficients as measured using event-driven molecular dynamics simulations. These results highlight that transition state theory can capture the interstitial dynamics in the hard-sphere model system. Additionally, we quantify the interactions between the interstitials. We find that, apart from excluded volume interactions, the interstitial-interstitial interactions are almost ideal in our system. Lastly, we show that the interstitial diffusivity can be inferred from the large-particle fluctuations alone, thus providing an empirical relationship between the large-particle fluctuations and the interstitial diffusivity.
Pheochromocytoma Multisystem Crisis Behaving Like Interstitial Pneumonia: An Autopsy Case
Nomoto, Yohta; Kawano, Kiyoshi; Fujisawa, Naoki; Yoshida, Keiko; Yamashita, Tomoko; Makita, Naoki; Takeshita, Hiroaki; Kamimori, Kimio; Yanagi, Shiro; Yoshiyama, Minoru
2017-01-01
Pheochromocytoma multisystem crisis is a rare and life-threatening disease that is associated with numerous symptoms and which is also difficult to diagnose. We herein report an autopsy case of a 61-year-old man who died due to pheochromocytoma multisystem crisis. The patient complained of vomiting and breathlessness. Computed tomography showed a shadow-like region with a similar appearance to interstitial pneumonia. The patient was diagnosed with takotsubo cardiomyopathy induced by severe lung disease based on the results of echocardiography and coronary angiography. The patient was treated for interstitial pneumonia. However, his condition rapidly deteriorated and he died 6 hours after arrival. We were later informed of his extremely high catecholamine serum levels. We found pheochromocytoma with hemorrhage at autopsy. The patient's lungs showed acute passive congestion with edema and extravasation. PMID:28090043
Serial Histopathological Examination of the Lungs of Mice Infected with Influenza A Virus PR8 Strain
Fukushi, Masaya; Ito, Tateki; Oka, Teruaki; Kitazawa, Toshio; Miyoshi-Akiyama, Tohru; Kirikae, Teruo; Yamashita, Makoto; Kudo, Koichiro
2011-01-01
Avian influenza H5N1 and pandemic (H1N1) 2009 viruses are known to induce viral pneumonia and subsequent acute respiratory distress syndrome (ARDS) with diffuse alveolar damage (DAD). The mortality rate of ARDS/DAD is extremely high, at approximately 60%, and no effective treatment for ARDS/DAD has been established. We examined serial pathological changes in the lungs of mice infected with influenza virus to determine the progress from viral pneumonia to ARDS/DAD. Mice were intranasally infected with influenza A/Puerto Rico/8/34 (PR8) virus, and their lungs were examined both macro- and micro-pathologically every 2 days. We also evaluated general condition, survival rate, body weight, viral loads in lung, and surfactant proteins in serum. As a result, all infected mice died within 9 days postinfection. At 2 days postinfection, inflammation in alveolar septa, i.e., interstitial pneumonia, was observed around bronchioles. From 4 to 6 days postinfection, interstitial pneumonia with alveolar collapse expanded throughout the lungs. From 6 to 9 days postinfection, DAD with severe alveolar collapse was observed in the lungs of all of dying and dead mice. In contrast, DAD was not observed in the live infected-mice from 2 to 6 days postinfection, despite their poor general condition. In addition, histopathological analysis was performed in mice infected with a dose of PR8 virus which was 50% of the lethal dose for mice in the 20-day observation period. DAD with alveolar collapse was observed in all dead mice. However, in the surviving mice, instead of DAD, glandular metaplasia was broadly observed in their lungs. The present study indicates that DAD with severe alveolar collapse is associated with death in this mouse infection model of influenza virus. Inhibition of the development of DAD with alveolar collapse may decrease the mortality rate in severe viral pneumonia caused by influenza virus infection. PMID:21701593
Spontaneous pneumomediastinum and subcutaneous emphysema in systemic lupus erythematosus
Ahmed, AlaEldin H; Awouda, Elrasheid A
2010-01-01
We report a case of a 29-year-old woman who is known to have systemic lupus erythematosus and idiopathic interstitial pneumonia; she presented with a 1-day history of substernal chest pain and increasing shortness of breath. On examination, she was found breathless, but was not distressed or afebrile or normotensive. Auscultation of the heart revealed a positive Hamman's sign. There was chest-wall crepitus, and auscultation of the lung showed bilateral crepitations. Full blood count and biochemical profile were unremarkable. Chest x-ray showed signs of idiopathic interstitial pneumonia in addition to pneumomediastinum (linear band of air within mediastinal planes and continuous diaphragm sign) and chest-wall subcutaneous emphysema. She was treated with high-concentration oxygen. A repeat chest x-ray 5 days later showed complete resolution of the pneumomediastinum and subcutaneous emphysema, but signs of idiopathic interstitial pneumonia continued to persist. PMID:22767622
Niemann-Pick type B in adulthood.
Simões, Rita Gonçalves; Maia, Helena
2015-02-05
Niemann-Pick disease (NPD) is a rare group of autosomal recessive disorders associated with intracellular deposition of sphingomyelin. NPD type B is a milder form, generally later in onset, with a good prognosis for survival into adulthood and usually with no neurological abnormalities. The authors describe the case of a 52-year-old man who presented with unexplained pancytopenia and splenomegaly. He was admitted to emergency splenectomy due to pathological splenic rupture. The histological findings showed diffuse histiocytosis, suggesting lysosomal storage disease. The NPD was confirmed when residual activity of acid sphingomyelinase in peripheral blood leucocytes and cultured skin fibroblasts was detected. Besides lipid abnormalities, the patient also had lipid interstitial pneumonia. There is no treatment for NPD. Management is based on surveillance and supportive care. The patient has reached the sixth decade of life with no symptoms and, despite the pneumonia and splenectomy, he still has a fairly healthy life. 2015 BMJ Publishing Group Ltd.
Idiopathic Interstitial Pneumonias
... 50 More than 60% Pulmonary rehabilitation Lung transplantation Pirfenidone or nintedanib 50–70% die in 5 years. ... In This Article Generic Name Select Brand Names Pirfenidone ESBRIET nintedanib OFEV Interstitial Lung Diseases Overview of ...
Gilman, Robert H; Tielsch, James M; Steinhoff, Mark; Figueroa, Dante; Rodriguez, Shalim; Caffo, Brian; Tracey, Brian; Elhilali, Mounya; West, James; Checkley, William
2012-01-01
Introduction WHO case management algorithm for paediatric pneumonia relies solely on symptoms of shortness of breath or cough and tachypnoea for treatment and has poor diagnostic specificity, tends to increase antibiotic resistance. Alternatives, including oxygen saturation measurement, chest ultrasound and chest auscultation, exist but with potential disadvantages. Electronic auscultation has potential for improved detection of paediatric pneumonia but has yet to be standardised. The authors aim to investigate the use of electronic auscultation to improve the specificity of the current WHO algorithm in developing countries. Methods This study is designed to test the hypothesis that pulmonary pathology can be differentiated from normal using computerised lung sound analysis (CLSA). The authors will record lung sounds from 600 children aged ≤5 years, 100 each with consolidative pneumonia, diffuse interstitial pneumonia, asthma, bronchiolitis, upper respiratory infections and normal lungs at a children's hospital in Lima, Peru. The authors will compare CLSA with the WHO algorithm and other detection approaches, including physical exam findings, chest ultrasound and microbiologic testing to construct an improved algorithm for pneumonia diagnosis. Discussion This study will develop standardised methods for electronic auscultation and chest ultrasound and compare their utility for detection of pneumonia to standard approaches. Utilising signal processing techniques, the authors aim to characterise lung sounds and through machine learning, develop a classification system to distinguish pathologic sounds. Data will allow a better understanding of the benefits and limitations of novel diagnostic techniques in paediatric pneumonia. PMID:22307098
Giant-cell interstitial pneumonia in a gas station worker.
Lee, S M; Moon, C H; Oh, Y B; Kim, H Y; Ahn, Y; Ko, E J; Joo, J E
1998-10-01
Giant-cell interstitial Pneumonia (GIP) is a very uncommon respiratory disease. The majority of cases of GIP are caused by exposure to cobalt, tungsten and other hard metals. In this report, we describe GIP in a patient who worked in gas station and dealt in propane gas vessels. He presented with clinical features of chronic interstitial lung disease and underwent an open lung biopsy that showed DIP-like reaction with large numbers of intra-alveolar macrophages and numerous large, multinucleated histiocytes which were admixed with the macrophages. Analysis of lung tissue for hard metals was done. Cobalt was the main component of detected hard metals. Corticosteroid therapy was started and he recovered fully.
NASA Astrophysics Data System (ADS)
Behera, Rakesh K.; Watanabe, Taku; Andersson, David A.; Uberuaga, Blas P.; Deo, Chaitanya S.
2016-04-01
Oxygen interstitials in UO2+x significantly affect the thermophysical properties and microstructural evolution of the oxide nuclear fuel. In hyperstoichiometric Urania (UO2+x), these oxygen interstitials form different types of defect clusters, which have different migration behavior. In this study we have used kinetic Monte Carlo (kMC) to evaluate diffusivities of oxygen interstitials accounting for mono- and di-interstitial clusters. Our results indicate that the predicted diffusivities increase significantly at higher non-stoichiometry (x > 0.01) for di-interstitial clusters compared to a mono-interstitial only model. The diffusivities calculated at higher temperatures compare better with experimental values than at lower temperatures (< 973 K). We have discussed the resulting activation energies achieved for diffusion with all the mono- and di-interstitial models. We have carefully performed sensitivity analysis to estimate the effect of input di-interstitial binding energies on the predicted diffusivities and activation energies. While this article only discusses mono- and di-interstitials in evaluating oxygen diffusion response in UO2+x, future improvements to the model will primarily focus on including energetic definitions of larger stable interstitial clusters reported in the literature. The addition of larger clusters to the kMC model is expected to improve the comparison of oxygen transport in UO2+x with experiment.
[Measures to be taken in adults with bronchiolitis].
De Crémoux, Hubert
2003-02-22
The majority of bronchial and interstitial diseases of the adult are accompanied by bronchiolar inflammation, but over time the use of the term "bronchiolitis" has been limited to a few specific affections. Bronchiolitis with predominantly alveolar involvement Some "bronchiolites" emphasize the problem of an interstitial pneumopathy, since the disease predominantly involves the alveolar spaces. Only a few bronchiolites are severely damaging: bronchiolitis obliterans with organizing pneumonia and interstitial pneumopathy with respiratory bronchiolitis. These predominantly alveolar affections reveal the clinical (crepitant rales), radiographic (multiple or even diffuse opacities), and functional aspects (restrictive ventilation problems). Brochiolitis with obstructive airway problems In this case the disease predominantly involves the bronchioles and spares the alveolar tissue. The term "bronchiolitis" is in this case perfectly justified. The clinical picture is evocative with obstructed airway and a clear pulmonary parenchyma on the thoracic x-ray. These affections belong to the obstructive broncho-pneumopathy group. The prototype is brochiolitis obliterans, the anatomic correlation of which is generally constrictive bronchiolitis obliterans. Occasionally primitive, it frequently complicates the progression of many morbid states (transplants, collagenosis, inhaled or ingested toxic substances.). Diffuse panbronchiolitis Other "bronchiolites" deviate from this framework and are accompanied by marked lesions of other respiratory tracts (membrane bronchioles, cartilage bronchi, mucosa, ear nose and throat). The prototype is panbronchiolitis, described in the Far East. It is exceptional in Europe, where similar but nosologically different clinical aspects are observed during various diseases: cystic fibrosis, Young's syndrome, hypogammaglobulinemia, bone marrow transplant, context of HIV or haemorrhagic recto-colitis.
Pneumonia in the immunocompetent patient.
Reynolds, J H; McDonald, G; Alton, H; Gordon, S B
2010-12-01
Pneumonia is an acute inflammation of the lower respiratory tract. Lower respiratory tract infection is a major cause of mortality worldwide. Pneumonia is most common at the extremes of life. Predisposing factors in children include an under-developed immune system together with other factors, such as malnutrition and over-crowding. In adults, tobacco smoking is the single most important preventable risk factor. The commonest infecting organisms in children are respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be broadly classified, on the basis of chest radiographic appearance, into lobar pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern. Lobar pneumonia is most commonly associated with community acquired pneumonia, bronchopneumonia with hospital acquired infection and an interstitial pattern with the so called atypical pneumonias, which can be caused by viruses or organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed with chest radiographs as the only form of imaging, but CT can detect pneumonia not visible on the chest radiograph and may be of value, particularly in the hospital setting. Complications of pneumonia include pleural effusion, empyema and lung abscess. The chest radiograph may initially indicate an effusion but ultrasound is more sensitive, allows characterisation in some cases and can guide catheter placement for drainage. CT can also be used to characterise and estimate the extent of pleural disease. Most lung abscesses respond to medical therapy, with surgery and image guided catheter drainage serving as options for those cases who do not respond.
Pneumonia in the immunocompetent patient
Reynolds, J H; Mcdonald, G; Alton, H; Gordon, S B
2010-01-01
Pneumonia is an acute inflammation of the lower respiratory tract. Lower respiratory tract infection is a major cause of mortality worldwide. Pneumonia is most common at the extremes of life. Predisposing factors in children include an under-developed immune system together with other factors, such as malnutrition and over-crowding. In adults, tobacco smoking is the single most important preventable risk factor. The commonest infecting organisms in children are respiratory viruses and Streptoccocus pneumoniae. In adults, pneumonia can be broadly classified, on the basis of chest radiographic appearance, into lobar pneumonia, bronchopneumonia and pneumonia producing an interstitial pattern. Lobar pneumonia is most commonly associated with community acquired pneumonia, bronchopneumonia with hospital acquired infection and an interstitial pattern with the so called atypical pneumonias, which can be caused by viruses or organisms such as Mycoplasma pneumoniae. Most cases of pneumonia can be managed with chest radiographs as the only form of imaging, but CT can detect pneumonia not visible on the chest radiograph and may be of value, particularly in the hospital setting. Complications of pneumonia include pleural effusion, empyema and lung abscess. The chest radiograph may initially indicate an effusion but ultrasound is more sensitive, allows characterisation in some cases and can guide catheter placement for drainage. CT can also be used to characterise and estimate the extent of pleural disease. Most lung abscesses respond to medical therapy, with surgery and image guided catheter drainage serving as options for those cases who do not respond. PMID:21088086
De Giacomi, Federica; Raghunath, Sushravya; Karwoski, Ronald; Bartholmai, Brian J; Moua, Teng
2018-03-01
Fibrotic interstitial lung diseases presenting with nonspecific and overlapping radiologic findings may be difficult to diagnose without surgical biopsy. We hypothesized that baseline quantifiable radiologic features and their short-term interval change may be predictive of underlying histologic diagnosis as well as long-term survival in idiopathic pulmonary fibrosis (IPF) presenting without honeycombing versus nonspecific interstitial pneumonia (NSIP). Forty biopsy-confirmed IPF and 20 biopsy-confirmed NSIP patients with available high-resolution chest computed tomography 4 to 24 months apart were studied. CALIPER software was used for the automated characterization and quantification of radiologic findings. IPF subjects were older (66 vs. 48; P<0.0001) with lower diffusion capacity for carbon monoxide and higher volumes of baseline reticulation (193 vs. 83 mL; P<0.0001). Over the interval period, compared with NSIP, IPF patients experienced greater functional decline (forced vital capacity, -6.3% vs. -1.7%; P=0.02) and radiologic progression, as noted by greater increase in reticulation volume (24 vs. 1.74 mL; P=0.048), and decrease in normal (-220 vs. -37.7 mL; P=0.045) and total lung volumes (-198 vs. 58.1 mL; P=0.03). Older age, male gender, higher reticulation volumes at baseline, and greater interval decrease in normal lung volumes were predictive of IPF. Both baseline and short-term changes in quantitative radiologic findings were predictive of mortality. Baseline quantitative radiologic findings and assessment of short-term disease progression may help characterize underlying IPF versus NSIP in those with difficult to differentiate clinicoradiologic presentations. Our study supports the possible utility of assessing serial quantifiable high-resolution chest computed tomographic findings for disease differentiation in these 2 entities.
Sex steroid receptor expression in idiopathic pulmonary fibrosis.
Mehrad, Mitra; Trejo Bittar, Humberto E; Yousem, Samuel A
2017-08-01
Usual interstitial pneumonia (UIP) is characterized by progressive scarring of the lungs and is associated with high morbidity and mortality despite therapeutic interventions. Sex steroid receptors have been demonstrated to play an important role in chronic lung conditions; however, their significance is unknown in patients with UIP. We retrospectively reviewed 40 idiopathic UIP cases for the expression of hormonal receptors. Forty cases including 10 normal lung, 10 cryptogenic organizing pneumonia, 10 idiopathic organizing diffuse alveolar damage, 7 hypersensitivity pneumonitis, and 3 nonspecific interstitial pneumonitis served as controls. Immunohistochemistry for estrogen receptor α, progesterone receptor (PR), and androgen receptor was performed in all groups. Expression of these receptors was assessed in 4 anatomic/pathologic compartments: alveolar and bronchiolar epithelium, arteries/veins, fibroblastic foci/airspace organization, and old scar. All UIPs (100%) stained positive for PR in myofibroblasts in the scarred areas, whereas among the control cases, only 1 nonspecific interstitial pneumonitis case stained focally positive and the rest were negative. PR was positive in myocytes of the large-sized arteries within the fibrotic areas in 31 cases (77.5%). PR was negative within the alveolar and bronchial epithelium, airspace organization, and center of fibroblastic foci; however, weak PR positivity was noted in the peripheral fibroblasts of the fibroblastic foci where they merged with dense fibrous connective tissue scar. All UIP and control cases were negative for androgen receptor and estrogen receptor α. This is the first study to show the expression of PR within the established fibrotic areas of UIP, indicating that progesterone may have profibrotic effects in UIP patients. Hormonal therapy by targeting PR could be of potential benefit in patients with UIP/IPF. Copyright © 2017 Elsevier Inc. All rights reserved.
Legionnaire's pneumonia: is there really an interstitial disease?
Godet, C; Frat, J P; Le Moal, G; Roblot, F; Michalakis, G; Cabon, E; Tasu, J P
2007-01-01
Legionella pneumonia is usually classified as "atypical pneumonia", which suggests a predominance of interstitial patterns in chest X-rays. Based on a selection of recent clinical cases and a brief review of the literature, the aim of the study is to clarify, how far the actual radiological findings would be consistent with these expectations. A retrospective analysis of 18 epidemic personal cases and a review of the literature data were performed to describe the chest X-ray findings of Legionella pneumophila (LP) community acquired pneumonia. X-ray review was performed simultaneously and in consensus by two radiologists (J.P.T., E.C.) and a physician (C.G.). From our series, 17 patients had an abnormal chest X-ray on admission. Among these pathological X-ray cases, infiltrates were more often confluent (n=16), or patchy (n=7), rather than interstitial (n=1). Fifteen patients had infiltrates involving the lower lung fields. Bilateral distribution of abnormalities and pleural effusion were each observed in three cases. Radiological findings deteriorated between the second and seventh days following admission, particularly in the form of patchy infiltrates with pleural effusion. The review of the literature is consistent with these findings, by reporting prevalent confluent or patchy infiltrates. These findings are consistent with the physiopathological particularity of this affection and incite us to avoid the classification "atypical pneumonia" in radiologic terminology. This term is more appropriate for clinical and microbiological use.
Smoking-related interstitial lung diseases.
Caminati, A; Graziano, P; Sverzellati, N; Harari, S
2010-12-01
In pulmonary pathology, a wide spectrum of morphological changes is related to the consequences of smoking, and recognizing them on surgical specimens and on small transbronchial biopsies represents a challenge for the pathologist. Respiratory bronchiolitis, also referred to as smoker's bronchiolitis, is a common histologic feature found in the lung tissue of cigarette smokers. When identified as the sole histopathologic finding in the clinical setting of symptomatic interstitial lung disease, a diagnosis of respiratory bronchiolitis-interstitial lung disease is made. Since smoking is recognized to cause a variety of histologic patterns encompassing respiratory bronchiolitis, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia and pulmonary Langerhans cell hystiocytosis, smoking-related interstitial lung disease may be a useful concept to keep in mind for the pathologists. The relationship of smoking with each of these entities has been largely established on the basis of epidemiologic evidence. Although they have been retained as distinct and separate conditions in various classifications of interstitial lung diseases, these entities share a number of clinical, radiologic, and pathologic features suggesting that they represent a spectrum of patterns of interstitial lung disease occurring in predisposed individuals who smoke. Evaluation of histologic features, particularly in surgical lung biopsy samples, is important in making the distinction between these disorders. However, even after tissue biopsy, it may sometimes be difficult to clearly separate these entities. Recently, respiratory bronchiolitis-interstitial lung disease with fibrosis has been described and postulated that this is a smoking-related condition distinct from fibrotic non-specific interstitial pneumonia.
[Airway-centered interstitial fibrosis related to exposure to fumes from cleaning products].
Serrano, Mario; Molina-Molina, María; Ramírez, José; Sánchez, Marcelo; Xaubet, Antoni
2006-10-01
Airway-centered interstitial fibrosis is a little known clinical entity that has only recently been described in the literature. Its pathology is characterized by bronchial fibrosis and localized interstitial pulmonary fibrosis around the airways. The disease has been associated with inhalation of a variety of substances, environmental or occupational, organic or inorganic. Clinical signs, radiographic manifestations, and lung function in patients with airway-centered interstitial fibrosis are similar to those of patients with idiopathic interstitial pneumonia. We describe a case of airway-centered interstitial fibrosis related to exposure to fumes from cleaning products.
Izumi, Yasumori; Akazawa, Manabu; Akeda, Yukihiro; Tohma, Shigeto; Hirano, Fuminori; Ideguchi, Haruko; Matsumura, Ryutaro; Miyamura, Tomoya; Mori, Shunsuke; Fukui, Takahiro; Iwanaga, Nozomi; Jiuchi, Yuka; Kozuru, Hideko; Tsutani, Hiroshi; Saisyo, Kouichirou; Sugiyama, Takao; Suenaga, Yasuo; Okada, Yasumasa; Katayama, Masao; Ichikawa, Kenji; Furukawa, Hiroshi; Kawakami, Kenji; Oishi, Kazunori; Migita, Kiyoshi
2017-01-25
Pneumococcal pneumonia is the most frequent form of pneumonia. We herein assessed the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in the prevention of pneumonia overall in rheumatoid arthritis (RA) patients at risk for infections. We hypothesized that PPSV23 vaccination is superior in preventing pneumococcal pneumonia compared with placebo in RA patients. A prospective, multicenter, double-blinded, randomized, placebo-controlled (1:1) trial was conducted across departments of rheumatology in Japanese National Hospital Organization hospitals. RA patients (n = 900) who had been treated with biological or immunosuppressive agents were randomly assigned PPSV23 or placebo (sodium chloride). The primary endpoints were the incidences of all-cause pneumonia and pneumococcal pneumonia. The secondary endpoint was death from pneumococcal pneumonia, all-cause pneumonia, or other causes. Cox regression models were used to estimate the risk of pneumonia overall for the placebo group compared with the vaccine group. Seventeen (3.7%) of 464 patients in the vaccine group and 15 (3.4%) of 436 patients in the placebo group developed pneumonia. There was no difference in the rates of pneumonia between the two study groups. The overall rate of pneumonia was 21.8 per 1000 person-years for patients with RA. The presence of interstitial pneumonia (hazard ratio: 3.601, 95% confidence interval: 1.547-8.380) was associated with an increased risk of pneumonia in RA patients. PPSV23 does not prevent against pneumonia overall in RA patients at relative risk for infections. Our results also confirm that the presence of interstitial lung disease is associated with pneumonia in Japanese patients with RA. UMIN-CTR UMIN000009566 . Registered 17 December 2012.
[Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].
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.
[The clinical study on KL-6 and SP-D in sera of patients with various pulmonary diseases].
Sugimoto, H; Okada, E; Hashimoto, N; Suzuki, S; Yoshida, H; Totani, Y; Ameshima, S; Ishizaki, T; Miyamori, I
2000-06-01
It has been reported that serum levels of KL-6 and surfactant protein D(SP-D) can be useful indicators for interstitial pneumonia(IP). In the present study, we evaluated the clinical significance of KL-6 and SP-D by measuring the serum levels of patients with various pulmonary diseases by enzyme-linked immunosorbent assay. Serum levels of KL-6 in patients with idiopathic interstitial pneumonia(IIP), collagen disease with interstitial pneumonia(CDIP), lung cancer(LC) and LC with idiopathic interstitial pneumonia were significantly higher than of those in healthy controls. Moreover, serum levels of KL-6 were significantly higher in patients with active IP than in those with inactive IP. Serum levels of SP-D in patients with IIP and CDIP were significantly higher than of those in healthy controls. When a cut-off level of KL-6 or SP-D in sera was defined as a value of healthy controls representing the means + 2SD, the serum KL-6 positive diagnostic rate for IP(79.2%) was higher than that of SP-D(66.7%). The SP-D positive diagnostic rate for lung diseases other than IP(11.6%) was lower than that of KL-6(34.9%). The serum concentration of KL-6 in patients with the pulmonary diseases significantly correlated with that of SP-D. These findings suggest that KL-6 may be superior in the sensitivity of IP and can be used to evaluate the disease activity of IP. In addition, SP-D may be more specific for IP than KL-6.
Expression of HSP47 in Usual Interstitial Pneumonia and Nonspecific Interstitial Pneumonia
Kakugawa, Tomoyuki; Mukae, Hiroshi; Hayashi, Tomayoshi; Ishii, Hiroshi; Nakayama, Seiko; Sakamoto, Noriho; Yoshioka, Sumako; Sugiyama, Kanako; Mine, Mariko; Mizuta, Yohei; Kohno, Shigeru
2005-01-01
Background Heat shock protein (HSP) 47, a collagen-specific molecular chaperone, is involved in the processing and/or secretion of procollagens, and its expression is increased in various fibrotic diseases. The aim of this study was to determine whether quantitative immunohistochemical evaluation of the expression levels of HSP47, type I procollagen and α-smooth muscle actin (SMA) allows the differentiation of idiopathic usual interstitial pneumonia (UIP) from UIP associated with collagen vascular disease (CVD) and idiopathic nonspecific interstitial pneumonia (NSIP). Methods We reviewed surgical lung biopsy specimens of 19 patients with idiopathic UIP, 7 with CVD-associated UIP and 16 with idiopathic NSIP and assigned a score for the expression of HSP47, type I procollagen and α-SMA in type II pneumocytes and/or lung fibroblasts (score 0 = no; 1 = weak; 2 = moderate; 3 = strong staining). Results The expression level of HSP47 in type II pneumocytes of idiopathic UIP was significantly higher than in CVD-associated UIP and idiopathic NSIP. The expression of HSP47 in fibroblasts was significantly higher in idiopathic UIP and idiopathic NSIP than in CVD-associated UIP. The expression of type I procollagen in type II pneumocytes was significantly higher in idiopathic UIP than in idiopathic NSIP. The expression of type I procollagen in fibroblasts was not different in the three groups, while the expression of α-SMA in fibroblasts was significantly higher in idiopathic UIP than in idiopathic NSIP. Conclusion Our results suggest the existence of different fibrotic pathways among these groups involved in the expression of HSP47 and type I procollagen. PMID:15955241
Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with AIDS.
Block, Brian L; Mehta, Tejas; Ortiz, Gabriel M; Ferris, Sean P; Vu, Thienkhai H; Huang, Laurence; Cattamanchi, Adithya
2017-01-01
Pneumocystis jirovecii pneumonia (PCP) typically presents as an interstitial and alveolar process with ground glass opacities on chest computed tomography (CT). The absence of ground glass opacities on chest CT is thought to have a high negative predictive value for PCP in individuals with AIDS. Here, we report a case of PCP in a man with AIDS who presented to our hospital with subacute shortness of breath and a nonproductive cough. While his chest CT revealed diffuse nodular rather than ground glass opacities, bronchoscopy with bronchoalveolar lavage and transbronchial biopsies confirmed the diagnosis of PCP and did not identify additional pathogens. PCP was not the expected diagnosis based on chest CT, but it otherwise fit well with the patient's clinical and laboratory presentation. In the era of combination antiretroviral therapy, routine prophylaxis for PCP, and increased use of computed tomography, it may be that PCP will increasingly present with nonclassical chest radiographic patterns. Clinicians should be aware of this presentation when selecting diagnostic and management strategies.
Unusual Radiographic Presentation of Pneumocystis Pneumonia in a Patient with AIDS
Mehta, Tejas; Ortiz, Gabriel M.; Ferris, Sean P.; Vu, Thienkhai H.; Huang, Laurence; Cattamanchi, Adithya
2017-01-01
Pneumocystis jirovecii pneumonia (PCP) typically presents as an interstitial and alveolar process with ground glass opacities on chest computed tomography (CT). The absence of ground glass opacities on chest CT is thought to have a high negative predictive value for PCP in individuals with AIDS. Here, we report a case of PCP in a man with AIDS who presented to our hospital with subacute shortness of breath and a nonproductive cough. While his chest CT revealed diffuse nodular rather than ground glass opacities, bronchoscopy with bronchoalveolar lavage and transbronchial biopsies confirmed the diagnosis of PCP and did not identify additional pathogens. PCP was not the expected diagnosis based on chest CT, but it otherwise fit well with the patient's clinical and laboratory presentation. In the era of combination antiretroviral therapy, routine prophylaxis for PCP, and increased use of computed tomography, it may be that PCP will increasingly present with nonclassical chest radiographic patterns. Clinicians should be aware of this presentation when selecting diagnostic and management strategies. PMID:29362681
A Patient with Non-Hodgkin Lymphoma and Nonspecific Interstitial Pneumonia during Ibrutinib Therapy.
Jungmann, Sven; Ludwig, Wolf-Dieter; Schönfeld, Nicolas; Blum, Torsten-Gerriet; Großwendt, Claudia; Boch, Christian; Rehbock, Beate; Griff, Sergej; Schmittel, Alexander; Bauer, Torsten T
2017-01-01
We present a 74-year-old male with nonspecific interstitial pneumonia (NSIP) during treatment with ibrutinib for mantle cell lymphoma. Previously, the patient had received six cycles of bendamustine and rituximab and six cycles of R-CHOP, followed by rituximab maintenance therapy. Respiratory tract complications of ibrutinib other than infectious pneumonia have not been mentioned in larger trials, but individual case reports hinted to a possible association with the development of pneumonitis. In our patient, the onset of alveolitis that progressed towards NSIP together with the onset of ibrutinib treatment suggests causality. One week after ibrutinib was discontinued, nasal symptoms resolved first. A follow-up CT showed a reduction in the reticular hyperdensities and ground-glass opacities, suggestive of restitution of the lung disease. To our knowledge, this is the first case showing a strong link between ibrutinib and interstitial lung disease, strengthening a previous report on subacute pneumonitis. Our findings have clinical implications because pulmonary side effects were reversible at this early stage. We, therefore, suggest close monitoring for respiratory side effects in patients receiving ibrutinib.
1987-08-31
PLEURISY AGE >69 AND/OR C. C. 1.1029 8.5 29 090 004 M SIMPLE PNEUMONIA + PLEURISY AGE 18-69 W/O C. C. 0.9849 7.6 28 091 004 M SIMPLE PNEUMONIA... PLEURISY AGE 0-17 0.5131 4.6 14 092 004 M INTERSTITIAL LUNG DISEASE AGE >69 AND/OR C. C. 1.0370 7.8 28 093 004 M INTERSTITIAL LUNG DISEASE AGE ា W/O C. C... PLEURISY AGE >69 AND/OR C. C. 224 684 668 675 673 679 -3 M SIMPLE PNEUMONIA + PLEURISY AGE 18-69 W/O C. C. 4370 3861 3877 3880 3889 3890 ;1 1:4 v SIMPLE
Foster, Derek M.; Martin, Luke G.; Papich, Mark G.
2016-01-01
Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points. PMID:26872361
Time scales of transient enhanced diffusion: Free and clustered interstitials
NASA Astrophysics Data System (ADS)
Cowern, N. E. B.; Huizing, H. G. A.; Stolk, P. A.; Visser, C. C. G.; de Kruif, R. C. M.; Kyllesbech Larsen, K.; Privitera, V.; Nanver, L. K.; Crans, W.
1996-12-01
Transient enhanced diffusion (TED) and electrical activation after nonamorphizing Si implantations into lightly B-doped Si multilayers shows two distinct timescales, each related to a different class of interstitial defect. At 700°C, ultrafast TED occurs within the first 15 s with a B diffusivity enhancement of > 2 × 10 5. Immobile clustered B is present at low concentration levels after the ultrafast transient and persists for an extended period (˜ 10 2-10 3 s). The later phase of TED exhibits a near-constant diffusivity enhancement of ≈ 1 × 10 4, consistent with interstitial injection controlled by dissolving {113} interstitial clusters. The relative contributions of the ultrafast and regular TED regimes to the final diffusive broadening of the B profile depends on the proportion of interstitials that escape capture by {113} clusters growing within the implant damage region upon annealing. Our results explain the ultrafast TED recently observed after medium-dose B implantation. In that case there are enough B atoms to trap a large proportion of interstitials in SiB clusters, and the remaining interstitials contribute to TED without passing through an intermediate {113} defect stage. The data on the ultrafast TED pulse allows us to extract lower limits for the diffusivities of the Si interstitial ( DI > 2 × 10 -10 cm 2s -1) and the B interstitial(cy) defect ( DBi > 2 × 10 -13 cm 2s -1) at 700°C.
Vildagliptin-induced acute lung injury: a case report.
Ohara, Nobumasa; Kaneko, Masanori; Sato, Kazuhiro; Maruyama, Ryoko; Furukawa, Tomoyasu; Tanaka, Junta; Kaneko, Kenzo; Kamoi, Kyuzi
2016-08-12
Dipeptidyl peptidase-4 inhibitors are a class of oral hypoglycemic drugs and are used widely to treat type 2 diabetes mellitus in many countries. Adverse effects include nasopharyngitis, headache, elevated serum pancreatic enzymes, and gastrointestinal symptoms. In addition, a few cases of interstitial pneumonia associated with their use have been reported in the Japanese literature. Here we describe a patient who developed drug-induced acute lung injury shortly after the administration of the dipeptidyl peptidase-4 inhibitor vildagliptin. A 38-year-old Japanese woman with diabetes mellitus developed acute respiratory failure 1 day after administration of vildagliptin. Chest computed tomography revealed nonsegmental ground-glass opacities in her lungs. There was no evidence of bacterial pneumonia or any other cause of her respiratory manifestations. After discontinuation of vildagliptin, she recovered fully from her respiratory disorder. She received insulin therapy for her diabetes mellitus, and her subsequent clinical course has been uneventful. The period of drug exposure in previously reported cases of patients with drug-induced interstitial pneumonia caused by dipeptidyl peptidase-4 inhibitor varied from several days to over 6 months. In the present case, our patient developed interstitial pneumonia only 1 day after the administration of vildagliptin. The precise mechanism of her vildagliptin-induced lung injury remains uncertain, but physicians should consider that dipeptidyl peptidase-4 inhibitor-induced lung injury, although rare, may appear acutely, even within days after administration of this drug.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sathiyanarayanan, Rajesh, E-mail: rajessat@in.ibm.com, E-mail: rajesh.sathiyanarayanan@gmail.com; Pandey, R. K.; Murali, K. V. R. M.
2015-01-21
Using first-principles simulations, we have computed incorporation energies and diffusion barriers of ammonia, the nitrogen molecule and atomic nitrogen in monoclinic hafnia (m-HfO{sub 2}). Our calculations show that ammonia is likely to dissociate into an NH{sub 2} molecular unit, whereas the nitrogen molecule remains as a molecule either in the interstitial space or at an oxygen lattice site. The lowest energy pathway for the diffusion of atomic nitrogen interstitials consists of the hopping of the nitrogen interstitial between neighboring three-coordinated lattice oxygen atoms that share a single Hf atom, and the barrier for such hops is determined by a switchingmore » mechanism. The substitutional nitrogen atom shows a preference for diffusion through the doubly positive oxygen vacancy-mediated mechanism. Furthermore, we have investigated the impact of nitrogen atoms on the diffusion barriers of oxygen and hydrogen interstitials in m-HfO{sub 2}. Our results show that nitrogen incorporation has a significant impact on the barriers for oxygen and hydrogen diffusion: nitrogen atoms attract oxygen and hydrogen interstitials diffusing in the vicinity, thereby slowing down (reducing) their diffusion (diffusion length)« less
Kinetic Monte Carlo (kMC) simulation of carbon co-implant on pre-amorphization process.
Park, Soonyeol; Cho, Bumgoo; Yang, Seungsu; Won, Taeyoung
2010-05-01
We report our kinetic Monte Carlo (kMC) study of the effect of carbon co-implant on the pre-amorphization implant (PAL) process. We employed BCA (Binary Collision Approximation) approach for the acquisition of the initial as-implant dopant profile and kMC method for the simulation of diffusion process during the annealing process. The simulation results implied that carbon co-implant suppresses the boron diffusion due to the recombination with interstitials. Also, we could compare the boron diffusion with carbon diffusion by calculating carbon reaction with interstitial. And we can find that boron diffusion is affected from the carbon co-implant energy by enhancing the trapping of interstitial between boron and interstitial.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Tabatowski, K.; Roggli, V.L.; Fulkerson, W.J.
A case of biopsy-proven giant cell interstitial pneumonia in a patient with occupational exposure to hard-metal dust is reported. Bronchial washings performed several days prior to open-lung biopsy yielded an almost exclusive population of nonpigmented alveolar macrophages and pleomorphic, phagocytic multinucleated giant cells. Microorganisms, viral inclusions in the giant cells, epithelioid histiocytes and well-formed granulomas were not seen. This cytologic picture strongly suggests the presence of giant cell interstitial pneumonia in a patient with restrictive lung disease, particularly when exposure to hard-metal dust is known or suspected. A specific diagnosis early in the course of the disease may facilitate removalmore » of the individual from the workplace and forestall the development of end-stage interstitial fibrosis. Additionally, the working environment may be modified to minimize inhalational exposure. Recognition of this entity by the cytopathologist may direct diagnostic efforts toward accurate histologic evaluation and the identification of particulates by microprobe analysis of either cellular or biopsy material.« less
Idiopathic pulmonary fibrosis.
Xaubet, Antoni; Ancochea, Julio; Molina-Molina, María
2017-02-23
Idiopathic pulmonary fibrosis is a fibrosing interstitial pneumonia associated with the radiological and/or histological pattern of usual interstitial pneumonia. Its aetiology is unknown, but probably comprises the action of endogenous and exogenous micro-environmental factors in subjects with genetic predisposition. Its diagnosis is based on the presence of characteristic findings of high-resolution computed tomography scans and pulmonary biopsies in absence of interstitial lung diseases of other aetiologies. Its clinical evolution is variable, although the mean survival rate is 2-5 years as of its clinical presentation. Patients with idiopathic pulmonary fibrosis may present complications and comorbidities which modify the disease's clinical course and prognosis. In the mild-moderate disease, the treatment consists of the administration of anti-fibrotic drugs. In severe disease, the best therapeutic option is pulmonary transplantation. In this paper we review the diagnostic and therapeutic aspects of the disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.
Usual interstitial pneumonia: typical, possible, and “inconsistent” patterns
Torres, Pedro Paulo Teixeira e Silva; Rabahi, Marcelo Fouad; Moreira, Maria Auxiliadora Carmo; Meirelles, Gustavo de Souza Portes; Marchiori, Edson
2017-01-01
ABSTRACT Idiopathic pulmonary fibrosis is a severe and progressive chronic fibrosing interstitial lung disease, a definitive diagnosis being established by specific combinations of clinical, radiological, and pathological findings. According to current international guidelines, HRCT plays a key role in establishing a diagnosis of usual interstitial pneumonia (UIP). Current guidelines describe three UIP patterns based on HRCT findings: a typical UIP pattern; a pattern designated “possible UIP”; and a pattern designated “inconsistent with UIP”, each pattern having important diagnostic implications. A typical UIP pattern on HRCT is highly accurate for the presence of histopathological UIP, being currently considered to be diagnostic of UIP. The remaining patterns require further diagnostic investigation. Other known causes of a UIP pattern include drug-induced interstitial lung disease, chronic hypersensitivity pneumonitis, occupational diseases (e.g., asbestosis), and connective tissue diseases, all of which should be included in the clinical differential diagnosis. Given the importance of CT studies in establishing a diagnosis and the possibility of interobserver variability, the objective of this pictorial essay was to illustrate all three UIP patterns on HRCT. PMID:29160385
The Role of Viral, Host, and Secondary Bacterial Factors in Influenza Pathogenesis
Kash, John C.; Taubenberger, Jeffery K.
2016-01-01
Influenza A virus infections in humans generally cause self-limited infections, but can result in severe disease, secondary bacterial pneumonias, and death. Influenza viruses can replicate in epithelial cells throughout the respiratory tree and can cause tracheitis, bronchitis, bronchiolitis, diffuse alveolar damage with pulmonary edema and hemorrhage, and interstitial and airspace inflammation. The mechanisms by which influenza infections result in enhanced disease, including development of pneumonia and acute respiratory distress, are multifactorial, involving host, viral, and bacterial factors. Host factors that enhance risk of severe influenza disease include underlying comorbidities, such as cardiac and respiratory disease, immunosuppression, and pregnancy. Viral parameters enhancing disease risk include polymerase mutations associated with host switch and adaptation, viral proteins that modulate immune and antiviral responses, and virulence factors that increase disease severity, which can be especially prominent in pandemic viruses and some zoonotic influenza viruses causing human infections. Influenza viral infections result in damage to the respiratory epithelium that facilitates secondary infection with common bacterial pneumopathogens and can lead to secondary bacterial pneumonias that greatly contribute to respiratory distress, enhanced morbidity, and death. Understanding the molecular mechanisms by which influenza and secondary bacterial infections, coupled with the role of host risk factors, contribute to enhanced morbidity and mortality is essential to develop better therapeutic strategies to treat severe influenza. PMID:25747532
Guimarães, J P; Febronio, A M B; Vergara-Parente, J E; Werneck, M R
2015-04-01
The parasitic fauna of cetaceans is an important tool for ecological studies, including analyses on the causes of death. Halocercus brasiliensis is a nematode frequently found in the bronchi and bronchioles of some cetaceans, and it is commonly associated with focal inflammation of the respiratory tract leading to bacterial pneumonia and septicemia and, sometimes, to death. The objective of this study was to report infections by H. brasiliensis in the respiratory tract of Delphinidae stranded on the northern seaside of Bahia, Sergipe, and south of Alagoas, all states in the northeast region of Brazil. A total of 30 individuals, 1 Feresa attenuate (pygmy killer whale), 9 Stenella clymene (Clymene dolphin), and 20 Sotalia guianensis (Guiana dolphin) were studied. In 16 of them, the presence of H. brasiliensis was observed with a mean intensity of 3.5 ± 0.6 (range 1-9) in the hosts. Macroscopically, parasitic calcified nodules, lung congestion, edema, and emphysema were observed. Histopathological examination showed interstitial and granulomatous pneumonia with multifocal infiltrates, discrete to moderate edema, congestion, diffuse hemorrhage, and foci of calcification. We conclude that parasitic pneumonia in the sampled individuals may have directly contributed to stranding and death of the animals.
Zinc diffusion in gallium arsenide and the properties of gallium interstitials
NASA Astrophysics Data System (ADS)
Bracht, H.; Brotzmann, S.
2005-03-01
We have performed zinc diffusion experiments in gallium arsenide at temperatures between 620°C and 870°C with a dilute Ga-Zn source. The low Zn partial pressure established during annealing realizes Zn surface concentrations of ⩽2×1019cm-3 , which lead to the formation of characteristic S-shaped diffusion profiles. Accurate modeling of the Zn profiles, which were measured by means of secondary ion mass spectroscopy, shows that Zn diffusion under the particular doping conditions is mainly mediated by neutral and singly positively charged Ga interstitials via the kick-out mechanism. We determined the temperature dependence of the individual contributions of neutral and positively charged Ga interstitials to Ga diffusion for electronically intrinsic conditions. The data are lower than the total Ga self-diffusion coefficient and hence consistent with the general interpretation that Ga diffusion under intrinsic conditions is mainly mediated by Ga vacancies. Our results disprove the general accepted interpretation of Zn diffusion in GaAs via doubly and triply positively charged Ga interstitials and solves the inconsistency related to the electrical compensation of the acceptor dopant Zn by the multiply charged Ga interstitials.
Chiba, Sahoko; Tsuchiya, Kimitake; Akashi, Takumi; Ishizuka, Masahiro; Okamoto, Tsukasa; Furusawa, Haruhiko; Tateishi, Tomoya; Kishino, Mitsuhiro; Miyazaki, Yasunari; Tateishi, Ukihide; Takemura, Tamiko; Inase, Naohiko
2016-06-01
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
2014-01-01
Background Clinical evaluation to differentiate the characteristic features of pulmonary fibrosis and emphysema is often difficult in patients with combined pulmonary fibrosis and emphysema (CPFE), but diagnosis of pulmonary fibrosis is important for evaluating treatment options and the risk of acute exacerbation of interstitial pneumonia of such patients. As far as we know, it is the first report describing a correlation among clinical, radiological, and whole-lung pathological features in an autopsy cases of CPFE patients. Methods Experts retrospectively reviewed the clinical charts and examined chest computed tomography (CT) images and pathological findings of an autopsy series of 22 CPFE patients, and compared these with findings from 8 idiopathic pulmonary fibrosis (IPF) patients and 17 emphysema-alone patients. Results All patients had a history of heavy smoking. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC%) was significantly lower in the emphysema-alone group than the CPFE and IPF-alone groups. The percent predicted diffusing capacity of the lung for carbon monoxide (DLCO%) was significantly lower in the CPFE group than the IPF- and emphysema-alone groups. Usual interstitial pneumonia (UIP) pattern was observed radiologically in 15 (68.2%) CPFE and 8 (100%) IPF-alone patients and was pathologically observed in all patients from both groups. Pathologically thick-cystic lesions involving one or more acini with dense wall fibrosis and occasional fibroblastic foci surrounded by honeycombing and normal alveoli were confirmed by post-mortem observation as thick-walled cystic lesions (TWCLs). Emphysematous destruction and enlargement of membranous and respiratory bronchioles with fibrosis were observed in the TWCLs. The cystic lesions were always larger than the cysts of honeycombing. The prevalence of both radiological and pathological TWCLs was 72.7% among CPFE patients, but no such lesions were observed in patients with IPF or emphysema alone (p = 0.001). The extent of emphysema in CPFE patients with TWCLs was greater than that in patients without such lesions. Honeycombing with emphysema was also observed in 11 CPFE patients. Conclusions TWCLs were only observed in the CPFE patients. They were classified as lesions with coexistent fibrosing interstitial pneumonia and emphysema, and should be considered an important pathological and radiological feature of CPFE. PMID:24972672
The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC
Jiang, Hao; Wang, Xing; Szlufarska, Izabela
2017-02-09
Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less
The multiple roles of small-angle tilt grain boundaries in annihilating radiation damage in SiC
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jiang, Hao; Wang, Xing; Szlufarska, Izabela
Lattice defects generated by radiation damage can diffuse to grain boundaries (GBs) and be annihilated at GBs. However, the precise role of GBs in annihilating the segregated defects remains unclear. Here, we employed multi-scale models to determine how interstitials are annihilated at small-angle tilt GBs (STGBs) in SiC. First of all, we found the pipe diffusion of interstitials in STGBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, we found both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled andmore » can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of STGBs in annihilating radiation damage. This model includes defect flux to GBs, pipe diffusion in STGBs, and the interaction of defects with jogs. The model predicts the role of STGBs in annihilating defects depends on the rate of defects segregation to and diffusion along STGBs. STGBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. As a result, when defect diffusivity is low, most of the defects segregated to STGBs are annihilated by dislocation climb.« less
Kuroda, Takeshi; Takeuchi, Hiroyuki; Nozawa, Yukiko; Sato, Hiroe; Nakatsue, Takeshi; Wada, Yoko; Moriyama, Hiroshi; Nakano, Masaaki; Narita, Ichiei
2016-04-26
Pneumocystis jirovecii pneumonia (PCP) is potentially fatal infectious complication in patients with rheumatoid arthritis (RA) during immunosuppressive therapy. Hospital survival due to human immunodeficiency virus-unrelated PCP reaches to 60%. The high mortality rate results from difficulties in establishing an early diagnosis, concurrent use of prophylactic drugs, possible bacterial coinfection. We herein report a case of PCP in RA patients who developed the architectural distortions of lung in spite of combined modality therapy. A 73-year-old Japanese woman with RA was admitted with shortness of breath. Five weeks previously, she had been started on etanercept in addition to methotrexate (MTX). Chest computed tomography (CT) demonstrated diffuse ground glass opacities distributed throughout the bilateral middle to lower lung fields, and serum β-D-glucan was elevated. Bronchoalveolar lavage fluid revealed no P. jirovecii, but the organism was detected by polymerase chain reaction method. Trimethoprim/sulfamethoxazole was administered with methylprednisolone pulse therapy. However, the follow-up chest X-ray and chest CT demonstrated aggravation of the pneumonia with architectural distortions. Additional direct hemoperfusion with polymyxin B-immobilized fibers and intravenous cyclophosphamide therapy were insufficiently effective, and the patient died on day 25. The architectural distortions of lung should be considered as a cause of death of PCP. For this reason, a high suspicion of this infectious complication must be kept in mind in order to establish an early diagnosis and treatment in patients with RA managed with MTX and biologics.
Pathology of lethal and sublethal doses of aerosolized ricin in rhesus macaques.
Bhaskaran, Manoj; Didier, Peter J; Sivasubramani, Satheesh K; Doyle, Lara A; Holley, Jane; Roy, Chad J
2014-01-01
Ricin toxin, a type 2 ribosome-inactivating protein and a category B bioterrorism agent, is produced from the seeds of castor oil plant (Ricinus communis). Chronic pathological changes in survivors of aerosolized ricin exposure have not been reported in primates. Here we compare and contrast the pathological changes manifested between rhesus macaques (RM) that succumbed to lethal dose of ricin (group I) and survivor RM exposed to low dose of ricin (group II). All animals in group I exhibited severe diffuse, necrotizing bronchiolitis and alveolitis with fibrinopurulent bronchointerstitial pneumonia, massive alveolar, perivascular and peribronchial/bronchiolar edema with hemorrhage, and necropurulent and hemorrhagic tracheobronchial lymphadenitis. All animals from group II had multifocal, fibrosing interstitial pneumonia with prominent alveolar histiocytosis and type II pneumocyte hyperplasia. Subacute changes like infiltration by lymphocytes and plasma cells and persistence of edematous fluid were occasionally present in lung and tracheobronchial lymph nodes. The changes appear to be a continuum wherein the inflammatory response shifts from an acute to subacute/chronic reparative process if the animals can survive the initial insult.
Interstitial Lung Disease due to Siderosis in a Lathe Machine Worker.
Gothi, D; Satija, B; Kumar, S; Kaur, Omkar
2015-01-01
Since its first description in 1936, siderosis of lung has been considered a benign pneumoconiosis due to absence of significant clinical symptoms or respiratory impairment. Subsequently, authors have questioned the non-fibrogenic property of iron. However, siderosis causing interstitial lung disease with usual interstitial pneumonia (UIP) pattern has not been described in the past. We report a case of UIP on high resolution computed tomography, proven to be siderosis on transbronchial lung biopsy in a lathe machine worker.
Kinetic Monte Carlo Simulation of Oxygen Diffusion in Ytterbium Disilicate
NASA Technical Reports Server (NTRS)
Good, Brian S.
2015-01-01
Ytterbium disilicate is of interest as a potential environmental barrier coating for aerospace applications, notably for use in next generation jet turbine engines. In such applications, the transport of oxygen and water vapor through these coatings to the ceramic substrate is undesirable if high temperature oxidation is to be avoided. In an effort to understand the diffusion process in these materials, we have performed kinetic Monte Carlo simulations of vacancy-mediated and interstitial oxygen diffusion in Ytterbium disilicate. Oxygen vacancy and interstitial site energies, vacancy and interstitial formation energies, and migration barrier energies were computed using Density Functional Theory. We have found that, in the case of vacancy-mediated diffusion, many potential diffusion paths involve large barrier energies, but some paths have barrier energies smaller than one electron volt. However, computed vacancy formation energies suggest that the intrinsic vacancy concentration is small. In the case of interstitial diffusion, migration barrier energies are typically around one electron volt, but the interstitial defect formation energies are positive, with the result that the disilicate is unlikely to exhibit experience significant oxygen permeability except at very high temperature.
Jacobs, Robert L; Andrews, Charles P
2003-02-01
Nonspecific interstitial pneumonia/fibrosis (NSIP) has been classified a form of idiopathic interstitial pneumonia/fibrosis. We have shown that cases of NSIP without demonstrable serum precipitins may be caused by inhalation of high levels of mold and/or bacteria in closed environments. We report a patient with a clinical and histopathologic diagnosis of NSIP without serum precipitins caused by a microbial contamination in her home. Her case was converted from an acute to an insidious clinical presentation by inadequate remediation. A prolonged avoidance-challenge technique demonstrated that this case of NSIP was a form of hypersensitivity pneumonia that was reversible by effective remediation. The patient was identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and a transbronchial lung biopsy. She was further evaluated with a detailed environmental history, serologic tests, and investigation of the home environment. An environmental avoidance and challenge technique was performed to confirm cause and effect and to determine that remediation had been effective. Review of the biopsy showed NSIP and failed to reveal any non-caseating granuloma formation. Investigation of the home revealed a Cladosporium species contamination of the air conditioning system and Penicillium species beneath an entryway carpet. Serum precipitins to commercial antigens of common mold to the south Texas area were negative. Avoidance and challenge techniques confirmed the home as the causative environment in this case of NSIP. The patient has been free of signs and symptoms and has taken no medication for interstitial lung disease over the past 30 months. Some cases of NSIP may be caused by inhalation of microbial antigen(s) in a closed environment. An environmental challenge technique was an effective method to determine the causative environment and confirm that remediation had been effective. Inadequate remediation may lead to symptomatic improvement, but may convert a patient from an acute to an insidious presenter. The environmental challenge obviates a need for specific challenges to determine specific causation. Remediation of or moving from an environmental contamination to achieve reversibility or prevent progression was the treatment of choice to avoid use of long-term immunosuppressive agents.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Ying; Field, Kevin G.; Allen, Todd R.
2016-02-23
A detailed analysis of the diffusion fluxes near and at grain boundaries of irradiated Fe–Cr–Ni alloys, induced by preferential atom-vacancy and atom-interstitial coupling, is presented. The diffusion flux equations were based on the Perks model formulated through the linear theory of the thermodynamics of irreversible processes. The preferential atom-vacancy coupling was described by the mobility model, whereas the preferential atom-interstitial coupling was described by the interstitial binding model. The composition dependence of the thermodynamic factor was modeled using the CALPHAD approach. The calculated fluxes up to 10 dpa suggested the dominant diffusion mechanism for chromium and iron is via vacancy,more » while that for nickel can swing from the vacancy to the interstitial dominant mechanism. The diffusion flux in the vicinity of a grain boundary was found to be greatly modified by the segregation induced by irradiation, leading to the oscillatory behavior of alloy compositions in this region.« less
Radiation-enhanced self- and boron diffusion in germanium
NASA Astrophysics Data System (ADS)
Schneider, S.; Bracht, H.; Klug, J. N.; Hansen, J. Lundsgaard; Larsen, A. Nylandsted; Bougeard, D.; Haller, E. E.
2013-03-01
We report experiments on proton radiation-enhanced self- and boron (B) diffusion in germanium (Ge) for temperatures between 515 ∘C and 720 ∘C. Modeling of the experimental diffusion profiles measured by means of secondary ion mass spectrometry is achieved on the basis of the Frenkel pair reaction and the interstitialcy and dissociative diffusion mechanisms. The numerical simulations ascertain concentrations of Ge interstitials and B-interstitial pairs that deviate by several orders of magnitude from their thermal equilibrium values. The dominance of self-interstitial related defects under irradiation leads to an enhanced self- and B diffusion in Ge. Analysis of the experimental profiles yields data for the diffusion of self-interstitials (I) and the thermal equilibrium concentration of BI pairs in Ge. The temperature dependence of these quantities provides the migration enthalpy of I and formation enthalpy of BI that are compared with recent results of atomistic calculations. The behavior of self- and B diffusion in Ge under concurrent annealing and irradiation is strongly affected by the property of the Ge surface to hinder the annihilation of self-interstitials. The limited annihilation efficiency of the Ge surface can be caused by donor-type surface states favored under vacuum annealing, but the physical origin remains unsolved.
Clinical utility of capillary polymerase chain reaction for diagnosis of Cytomegalovirus pneumonia.
Honda, J; Yonemitsu, J; Kitajima, H; Yosida, N; Fumirori, T; Oizumi, K
2001-01-01
The purpose of this retrospective study was to assess the diagnostic efficacy of CMV DNA detection by capillary PCR in patients with interstitial pneumonia. Of 882 samples taken from 363 patients, 317 were obtained from sputum, 94 from BAL fluid, 291 from blood and 180 from urine. PCR for CMV was positive in 58 samples (6.6%), with positive detection for 6.9% of sputum, 10.6% of BAL fluid, 4.1% of blood and 7.8% of urine samples. CMV pneumonia was diagnosed retrospectively in 34 (9.4%) of the 363 patients by demonstration of CMV antigen-positive cytomegalic inclusion bodies in lung tissue sections. The positive and negative predictive values were 100% (10/10) and 98.8% (83/84) for the BAL fluid samples and 95.5% (21/22) and 99.7% (294/295) for the sputum samples, respectively. Clinical sensitivity and specificity were 90.9% (10/11) and 100% (83/83) for the BAL fluid samples and 95.5% (21/22) and 99.7% (294/295) for the sputum samples, respectively. However, the blood and urine samples showed poor clinical sensitivity and low positive predictive values. We suggest that the use of capillary PCR for BAL fluid and sputum samples is very useful for diagnosing CMV pneumonia in patients with interstitial pneumonia in whom CMV pneumonia is suspected.
Annihilating vacancies via dynamic reflection and emission of interstitials in nano-crystal tungsten
NASA Astrophysics Data System (ADS)
Li, Xiangyan; Duan, Guohua; Xu, Yichun; Zhang, Yange; Liu, Wei; Liu, C. S.; Liang, Yunfeng; Chen, Jun-Ling; Luo, G.-N.
2017-11-01
Radiation damage not only seriously degrades the mechanical properties of tungsten (W) but also enhances hydrogen retention in the material. Introducing a large amount of defect sinks, e.g. grain boundaries (GBs) is an effective method for improving radiation-resistance of W. However, the mechanism by which the vacancies are dynamically annihilated at long timescale in nano-crystal W is still not clear. The dynamic picture for eliminating vacancies with single interstitials and small interstitial-clusters has been investigated by combining molecular dynamics, molecular statics and object Kinetic Monte Carlo methods. On one hand, the annihilation of bulk vacancies was enhanced due to the reflection of an interstitial-cluster of parallel ≤ft< 1 1 1 \\right> crowdions by the GB. The interstitial-cluster was observed to be reflected back into the grain interior when approaching a locally dense GB region. Near this region, the energy landscape for the interstitial was featured by a shoulder, different to the decreasing energy landscape of the interstitial near a locally loose region as indicative of the sink role of the GB. The bulk vacancy on the reflection path was annihilated. On the other hand, the dynamic interstitial emission efficiently anneals bulk vacancies. The single interstitial trapped at the GB firstly moved along the GB quickly and clustered to be the di-interstitial therein, reducing its mobility to a value comparable to that that for bulk vacancy diffusion. Then, the bulk vacancy was recombined via the coupled motion of the di-interstitial along the GB, the diffusion of the vacancy towards the GB and the accompanying interstitial emission. These results suggest that GBs play an efficient role in improving radiation-tolerance of nano-crystal W via reflecting highly-mobile interstitials and interstitial-clusters into the bulk and annihilating bulk vacancies, and via complex coupling of in-boundary interstitial diffusion, clustering of the interstitial and vacancy diffusion in the bulk.
Prevalence of Pneumocystis jirovecii pneumonia (2010-2013): the first Croatian report.
Babic-Erceg, Andrea; Vilibic-Cavlek, Tatjana; Erceg, Marijan; Mlinaric-Missoni, Emilija; Begovac, Josip
2014-06-01
Pneumocystis jirovecii is an important cause of interstitial pneumonia particularly among immunocompromised hosts. We analysed the prevalence of P. jirovecii pneumonia (PCP) among HIV-infected and HIV-uninfected patients presented with interstitial pneumonia or acute respiratory syndrome hospitalized in six Croatian tertiary care hospitals. Over four-year period (2010-2013), a total of 328 lower respiratory tract samples: 253 (77.1%) bronchoalveolar lavage fluid, 43 (13.1%) tracheal aspirates and 32 (9.8%) bronchial aspirates from 290 patients were examined by real-time polymerase chain reaction (PCR). PCP was detected in 23 (7.9%) patients. The prevalence of PCP differed significantly among tested groups (χ2 = 95.03; d.f. = 3; p < 0.001). HIV-infected patients were more often positive (56.6%, 95%CI = 37.3-72.4) compared to other groups (patients with malignant disease 7.7%, 95%CI = 2.6-20.3; transplant patients 7.7%, 95%CI = 2.2-24.1; patients with other diagnosis 1.5%, 95%CI = 0.5-4.4). Majority of HIV-positive patients (80%) were newly diagnosed cases. Our results indicate that HIV-infected patients still represents the main risk group for P. jirovecii infection. PCP is responsible for pneumonia in 56.6% HIV-positive patients in Croatia, primarily those who do not know that they are HIV infected.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Levenson, S.M.; Warren, R.D.; Richman, S.D.
The potentially fatal interstitial pneumonia of Pneumocystis carinii is a frequent opportunistic invader of patients treated for malignancy with immunosuppressive and cytotoxic agents. Generalized Ga-67 pulmonary localization which is markedly disproportionate to the clinical and radiographic findings has led to earlier diagnoses by open lung biopsy in this setting. The potential usefulness of gallium scintigraphy in patients with suspected P. carinii pneumonia is presented. (auth)
Smoking related idiopathic interstitial pneumonia: Results of an ERS/ATS Task Force
Flaherty, Kevin R.; Fell, Charlene; Aubry, Marie-Christine; Brown, Kevin; Colby, Thomas; Costabel, Ulrich; Franks, Teri J.; Gross, Barry H; Hansell, David M.; Kazerooni, Ella; Kim, Dong Soon; King, Talmadge E.; Kitachi, Masanori; Lynch, David; Myers, Jeff; Nagai, Sonoko; Nicholson, Andrew G.; Poletti, Venerino; Raghu, Ganesh; Selman, Moises; Toews, Galen; Travis, William; Wells, Athol U.; Vassallo, Robert; Martinez, Fernando J.
2015-01-01
Background Cigarette smoking is a key factor in the development of numerous pulmonary diseases. Methods An international group of clinicians, radiologists, and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking related features in patients with a history of smoking (n=41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n=100) to participants blinded to smoking history. Finally, investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Results Phase 1 suggested that preserved forced vital capacity with disproportionately reduced DLCO, various radiographic and histopathologic findings were smoking related features. In Phase 2 the kappa among clinicians was 0.16 (95% CI 0.11 – 0.21), among the pathologists 0.36 (95% CI 0.32 – 0.34) and among the radiologists 0.43 (95% CI 0.35 – 0.52) for smoking related features. Eight of the 100 cases were felt to represent a potential smoking related interstitial lung disease. Conclusion Smoking related features of interstitial lung disease were identified in a minority of smokers and are not specific for smoking. This study is limited by its retrospective design and the potential for recall bias of smoking history and lack of information on second had smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease. PMID:25063244
Hwang, Jeong-Hwa; Misumi, Shigeki; Curran-Everett, Douglas; Brown, Kevin K; Sahin, Hakan; Lynch, David A
2011-08-01
The aim of this study was to evaluate the prognostic implications of computed tomography (CT) and physiologic variables at baseline and on sequential evaluation in patients with fibrosing interstitial pneumonia. We identified 72 patients with fibrosing interstitial pneumonia (42 with idiopathic disease, 30 with collagen vascular disease). Pulmonary function tests and CT were performed at the time of diagnosis and at a median follow-up of 12 months, respectively. Two chest radiologists scored the extent of specific abnormalities and overall disease on baseline and follow-up CT. Rate of survival was estimated using the Kaplan-Meier method. Three Cox proportional hazards models were constructed to evaluate the relationship between CT and physiologic variables and rate of survival: model 1 included only baseline variables, model 2 included only serial change variables, and model 3 included both baseline and serial change variables. On follow-up CT, the extent of mixed ground-glass and reticular opacities (P<0.001), pure reticular opacity (P=0.04), honeycombing (P=0.02), and overall extent of disease (P<0.001) was increased in the idiopathic group, whereas these variables remained unchanged in the collagen vascular disease group. Patients with idiopathic disease had a shorter rate of survival than those with collagen vascular disease (P=0.03). In model 1, the extent of honeycombing on baseline CT was the only independent predictor of mortality (P=0.02). In model 2, progression in honeycombing was the only predictor of mortality (P=0.005). In model 3, baseline extent of honeycombing and progression of honeycombing were the only independent predictors of mortality (P=0.001 and 0.002, respectively). Neither baseline nor serial change physiologic variables, nor the presence of collagen vascular disease, was predictive of rate of survival. The extent of honeycombing at baseline and its progression on follow-up CT are important determinants of rate of survival in patients with fibrosing interstitial pneumonia.
Intraluminal fibrosis in interstitial lung disorders.
Basset, F.; Ferrans, V. J.; Soler, P.; Takemura, T.; Fukuda, Y.; Crystal, R. G.
1986-01-01
The histopathologic and ultrastructural features of intraluminal organizing and fibrotic changes were studied in open lung biopsies and autopsy specimens from 373 patients with interstitial lung disorders, including hypersensitivity pneumonitis (n = 44), idiopathic pulmonary fibrosis (n = 92), collagen-vascular diseases (n = 20), chronic eosinophilic pneumonia (n = 10), pulmonary histiocytosis X (n-90), pulmonary sarcoidosis (n = 62), pneumoconioses (n = 25), Legionnaire's disease (n = 5), drug- and toxin-induced pneumonitis (n = 4), radiation-induced pneumonitis (n = 2), lymphangioleiomyomatosis (n = 11), and chronic organizing pneumonia of unknown cause (n = 8). Three patterns of intraluminal organization and fibrosis were recognized: 1) intraluminal buds, which partially filled the alveoli, alveolar ducts and/or distal bronchioles; 2) obliterative changes, in which loose connective tissue masses obliterated the lumens of alveoli, alveolar ducts or distal bronchioles, and 3) mural incorporation of previously intraluminal connective tissue masses, which fused with alveolar, alveolar ductal, or bronchiolar structures and frequently became reepithelialized. All three patterns had common morphologic features, suggesting that, regardless of their severity, they resulted from a common pathogenetic mechanism, ie, the migration of activated connective tissue cells, through defects in the epithelial lining and its basement membrane, from the interstitial into the intraluminal compartment. Intraluminal buds were observed most frequently in hypersensitivity pneumonitis, chronic eosinophilic pneumonia, and organizing pneumonia of unknown cause. Mural incorporation and, to a lesser extent, obliterative changes were observed in most interstitial disorders and were very prominent in idiopathic pulmonary fibrosis. Mural incorporation and obliterative changes play an important role in pulmonary remodeling, especially when several adjacent alveoli and/or other air spaces are involved. Under these circumstances, intraluminal organization can mediate the fusion of adjacent alveolar structures by intraluminal connective tissue. Images Figure 15 Figure 9 Figure 10 Figure 16 Figure 17 Figure 1 Figure 2 Figure 3 Figure 4 Figure 18 Figure 5 Figure 6 Figure 7 Figure 8 Figure 19 Figure 20 Figure 11 Figure 12 Figure 13 Figure 14 PMID:3953768
Isaac, Barney Thomas Jesudason; Thangakunam, Balamugesh; Cherian, Rekha A; Christopher, Devasahayam Jesudas
2015-01-01
For the follow-up of patients with idiopathic interstitial pneumonias (IIP), it is unclear which parameters of pulmonary function tests (PFT) and exercise testing would correlate best with high-resolution computed tomography (HRCT).. To find out the correlation of symptom scores, PFTs and exercise testing with HRCT scoring in patients diagnosed as idiopathic interstitial pneumonia. Cross-sectional study done in pulmonary medicine outpatients department of a tertiary care hospital in South India. Consecutive patients who were diagnosed as IIP by a standard algorithm were included into the study. Cough and dyspnea were graded for severity and duration. Pulmonary function tests and exercise testing parameters were noted. HRCT was scored based on an alveolar score, an interstitial score and a total score. The HRCT was correlated with each of the clinical and physiologic parameters. Pearson's/Spearman's correlation coefficient was used for the correlation of symptoms and parameters of ABG, PFT and 6MWT with the HRCT scores. A total of 94 patients were included in the study. Cough and dyspnea severity (r = 0.336 and 0.299), FVC (r = -0.48), TLC (r = -0.439) and DLCO and distance saturation product (DSP) (r = -0.368) and lowest saturation (r = -0.324) had significant correlation with total HRCT score. Among these, DLCO, particularly DLCO corrected % of predicted, correlated best with HRCT score (r = -0.721).. Symptoms, PFT and exercise testing had good correlation with HRCT. DLCO corrected % of predicted correlated best with HRCT.
Behzad, A R; Chu, F; Walker, D C
1996-05-01
Previous findings have shown that pulmonary fibroblasts are associated with preexisting holes in the endothelial and epithelial basal laminae through which neutrophils appear to enter and leave the interstitium as they migrate from capillaries to alveoli. To determine their role in neutrophil migration, fibroblast organization within the interstitium was assessed by transmission electron microscope observations of serial-sectioned rabbit lung tissue. Interstitial fibroblasts were found to physically interconnect the endothelial basal lamina holes to epithelial basal lamina holes. Morphometric assessment of rabbit lung tissue instilled with Streptococcus pneumoniae revealed that approximately 70% of the surface area density of migrating neutrophils is in close contact (15 nm or less) with interstitial fibroblasts and extracellular matrix elements (30 and 40%, respectively). Although migrating neutrophils were close enough to adhere to both fibroblasts and extracellular elements, the interstitial fibroblasts are organized in a manner that would allow them to provide directional information to the neutrophils. A model illustrating this process is proposed.
Okuda, Miyuki; Kashio, Makoto; Aitani, Masakazu; Nakanishi, Daisuke; Tanaka, Nobuya; Kimura, Kentaro
2009-07-01
The patient was a 70-year-old man who had been given a diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and had been placed on low-dose steroid therapy in the Department of Orthopedics. During treatment, sudden fever, hypoxemia and chest radiography-confirmed interstitial shadows throughout the lung fields were noted, and the patient was referred to the Department of Internal Medicine. RS3PE complicated by interstitial pneumonia was diagnosed, and steroid pulse therapy and immunosuppressant therapy were initiated. In the present case, soluble interleukin-2 receptor (sIL-2R) proved useful for assessing symptoms. To the best of our knowledge, RS3PE syndrome complicated by pulmonary lesions and accompanied by severe acute respiratory failure requiring noninvasive positive-pressure ventilation has not previously been reported, and this rare case is discussed with reference to the literature.
Liang, Xing; Wang, Ken Kang-Hsin; Zhu, Timothy C.
2013-01-01
Interstitial diffuse optical tomography (DOT) has been used to characterize spatial distribution of optical properties for prostate photodynamic therapy (PDT) dosimetry. We have developed an interstitial DOT method using cylindrical diffuse fibers (CDFs) as light sources, so that the same light sources can be used for both DOT measurement and PDT treatment. In this novel interstitial CDF-DOT method, absolute light fluence per source strength (in unit of 1/cm2) is used to separate absorption and scattering coefficients. A mathematical phantom and a solid prostate phantom including anomalies with known optical properties were used, respectively, to test the feasibility of reconstructing optical properties using interstitial CDF-DOT. Three dimension spatial distributions of the optical properties were reconstructed for both scenarios. Our studies show that absorption coefficient can be reliably extrapolated while there are some cross talks between absorption and scattering properties. Even with the suboptimal reduced scattering coefficients, the reconstructed light fluence rate agreed with the measured values to within ±10%, thus the proposed CDF-DOT allows greatly improved light dosimetry calculation for interstitial PDT. PMID:23629149
Impact of clinical history on chest radiograph interpretation.
Test, Matthew; Shah, Samir S; Monuteaux, Michael; Ambroggio, Lilliam; Lee, Edward Y; Markowitz, Richard I; Bixby, Sarah; Diperna, Stephanie; Servaes, Sabah; Hellinger, Jeffrey C; Neuman, Mark I
2013-07-01
The inclusion of clinical information may have unrecognized influence in the interpretation of diagnostic testing. The objective of the study was to determine the impact of clinical history on chest radiograph interpretation in the diagnosis of pneumonia. Prospective case-based study. Radiologists interpreted 110 radiographs of children evaluated for suspicion of pneumonia. Clinical information was withheld during the first interpretation. After 6 months the radiographs were reviewed with clinical information. Radiologists reported on pneumonia indicators described by the World Health Organization (ie, any infiltrate, alveolar infiltrate, interstitial infiltrate, air bronchograms, hilar adenopathy, pleural effusion). Children's Hospital of Philadelphia and Boston Children's Hospital. Six board-certified radiologists. Inter- and inter-rater reliability were assessed using the kappa statistic. The addition of clinical history did not have a substantial impact on the inter-rater reliability in the identification of any infiltrate, alveolar infiltrate, interstitial infiltrate, pleural effusion, or hilar adenopathy. Inter-rater reliability in the identification of air bronchograms improved from fair (k = 0.32) to moderate (k = 0.53). Intra-rater reliability for the identification of alveolar infiltrate remained substantial to almost perfect for all 6 raters with and without clinical information. One rater had a decrease in inter-rater reliability from almost perfect (k = 1.0) to fair (k = 0.21) in the identification of interstitial infiltrate with the addition of clinical history. Alveolar infiltrate and pleural effusion are findings with high intra- and inter-rater reliability in the diagnosis of bacterial pneumonia. The addition of clinical information did not have a substantial impact on the reliability of these findings. © 2012 Society of Hospital Medicine.
Ebisutani, Chikara; Ito, Isao; Kitaichi, Masanori; Tanabe, Naoya; Mishima, Michiaki; Kadowaki, Seizo
2016-07-01
We report the first case of non-specific interstitial pneumonia (NSIP) in a patient with cancer-associated myositis (CAM) that emerged along with the recurrence of the cancer. A 60-year-old woman, with a history of partial gastrectomy for gastric cancer 11 years ago, presented with exertional dyspnea with anti-Jo-1 antibody-positive myositis. Surgical lung biopsy showed NSIP with metastatic gastric cancer. Accordingly, her condition was diagnosed as CAM with cancer recurrence. In patients with a history of cancer, development of myositis may indicate cancer recurrence; therefore, careful observation would be necessary. Copyright © 2016 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Sim, Jae Kyeom; Oh, Jee Youn; Lee, Eun Joo; Hur, Gyu Young; Lee, Seung Heon; Lee, Sung Yong; Lee, Sang Yeub; Kim, Je Hyeong; Shin, Chol; Shim, Jae Jeong; In, Kwang Ho; Kang, Kyung Ho; Min, Kyung Hoon
2016-05-01
Acute exacerbation and bacterial pneumonia are major life-threatening conditions in patients with interstitial lung disease (ILD). The rapid recognition of these 2 different conditions is important for their proper treatment. An elevated procalcitonin (PCT) level is commonly detected in patients with bacterial infections. This study assessed the usefulness of the serum PCT level as a biomarker for the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. In this prospective observational study, we enrolled patients with ILD who had experienced recently progressive dyspnea and exhibited new infiltrations on chest radiographs. We classified these patients into an acute exacerbation group and a bacterial pneumonia group and compared their baseline characteristics and laboratory parameters, including the PCT level. Of 21 patients with ILD, 9 patients had bacterial pneumonia. Both the groups showed similar baseline characteristics. The bacterial pneumonia group demonstrated a high PCT level. The PCT level in the acute exacerbation group was significantly lower than that in the bacterial pneumonia group (0.05 versus 0.91ng/mL, respectively; P < 0.001). Other parameters, such as the C-reactive protein level, leukocyte count and body temperature, were also lower in the acute exacerbation group. At a cutoff value of 0.1ng/mL, the sensitivity, specificity and negative predictive values of the serum PCT level were 88.9%, 100.0% and 92.3%, respectively. These findings suggest that the serum PCT level is useful in the differential diagnosis of acute exacerbation and bacterial pneumonia in patients with ILD. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.
The relevance of light diffusion profiles for interstitial PDT using light-diffusing optical fibers
NASA Astrophysics Data System (ADS)
Stringasci, Mirian D.; Fortunato, Thereza C.; Moriyama, Lilian T.; Vollet Filho, José Dirceu; Bagnato, Vanderlei S.; Kurachi, Cristina
2017-02-01
Photodynamic therapy (PDT) is a technique used for several tumor types treatment. Light penetration on biological tissue is one limiting factor for PDT applied to large tumors. An alternative is using interstitial PDT, in which optical fibers are inserted into tumors. Cylindrical diffusers have been used in interstitial PDT. Light emission of different diffusers depends on the manufacturing process, size and optical properties of fibers, which make difficult to establish an adequate light dosimetry, since usually light profile is not designed for direct tissue-fiber contact. This study discusses the relevance of light distribution by a cylindrical diffuser into a turbid lipid emulsion solution, and how parts of a single diffuser contribute to illumination. A 2 cm-long cylindrical diffuser optical fiber was connected to a diode laser (630 nm), and the light spatial distribution was measured by scanning the solution with a collection probe. From the light field profile generated by a 1 mm-long intermediary element of a 20 mm-long cylindrical diffuser, recovery of light distribution for the entire diffuser was obtained. PDT was performed in rat healthy liver for a real treatment outcome analysis. By using computational tools, a typical necrosis profile generated by the irradiation with such a diffuser fiber was reconstructed. The results showed that it was possible predicting theoretically the shape of a necrosis profile in a healthy, homogeneous tissue with reasonable accuracy. The ability to predict the necrosis profile obtained from an interstitial illumination by optical diffusers has the potential improve light dosimetry for interstitial PDT.
NASA Astrophysics Data System (ADS)
Ngau, Julie L.; Griffin, Peter B.; Plummer, James D.
2001-08-01
Recent work has indicated that the suppression of boron transient enhanced diffusion (TED) in carbon-rich Si is caused by nonequilibrium Si point defect concentrations, specifically the undersaturation of Si self-interstitials, that result from the coupled out-diffusion of carbon interstitials via the kick-out and Frank-Turnbull reactions. This study of boron TED reduction in Si1-x-yGexCy during 750 °C inert anneals has revealed that the use of an additional reaction that further reduces the Si self-interstitial concentration is necessary to describe accurately the time evolved diffusion behavior of boron. In this article, we present a comprehensive model which includes {311} defects, boron-interstitial clusters, a carbon kick-out reaction, a carbon Frank-Turnbull reaction, and a carbon interstitial-carbon substitutional (CiCs) pairing reaction that successfully simulates carbon suppression of boron TED at 750 °C for anneal times ranging from 10 s to 60 min.
The pathological features of idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas.
Kojima, Yoko; Okudela, Koji; Matsumura, Mai; Omori, Takahiro; Baba, Tomohisa; Sekine, Akimasa; Woo, Tetsukan; Umeda, Shigeaki; Takemura, Tamiko; Mitsui, Hideaki; Suzuki, Takehisa; Tateishi, Yoko; Iwasawa, Tae; Arai, Hiromasa; Tajiri, Michihiko; Ogura, Takashi; Kameda, Yoichi; Masuda, Munetaka; Ohashi, Kenich
2017-03-01
To investigate the pathological features of idiopathic interstitial pneumonia (IIP)-associated pulmonary adenocarcinoma. Surgically resected adenocarcinomas associated with IIP (the IIP group) and adenocarcinomas without IIP (the non-IIP group) were subjected to analysis. Adenocarcinomas in the IIP group were subdivided into two groups: one group included tumours connected to bronchiolar metaplasia in honeycomb lesions (the H-IIP group), and the other included tumours unrelated to honeycomb lesions (the NH-IIP group). Histomorphological appearance and immunohistochemical expression were compared among the H-IIP group, the NH-IIP group, and the non-IIP group. Most of the tumour cells in the H-IIP group had a tall, columnar shape that showed similar features to proximal bronchial epithelium, whereas tumour cells in the NH-IIP group and the non-IIP group had a club-like shape that showed similar features to respiratory bronchiolar/alveolar epithelium. Adenocarcinomas in the H-IIP group tended to be negative for thyroid transcription factor-1 (TTF-1) and positive for hepatocyte nuclear factor-4α (HNF-4α). The frequency of EGFR mutations was significantly lower in adenocarcinomas in the H-IIP group, although the frequencies of KRAS and ALK mutations did not differ among the three groups. Idiopathic interstitial pneumonia-associated pulmonary adenocarcinomas, especially those arising from honeycomb lesions, have distinct pathological features. © 2016 John Wiley & Sons Ltd.
Rare variants in RTEL1 are associated with familial interstitial pneumonia.
Cogan, Joy D; Kropski, Jonathan A; Zhao, Min; Mitchell, Daphne B; Rives, Lynette; Markin, Cheryl; Garnett, Errine T; Montgomery, Keri H; Mason, Wendi R; McKean, David F; Powers, Julia; Murphy, Elissa; Olson, Lana M; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R; Lancaster, Lisa H; Steele, Mark P; Brown, Kevin K; Schwarz, Marvin I; Fingerlin, Tasha E; Schwartz, David A; Lawson, William E; Loyd, James E; Zhao, Zhongming; Phillips, John A; Blackwell, Timothy S
2015-03-15
Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis.
NASA Astrophysics Data System (ADS)
Bonafos, C.; Alquier, D.; Martinez, A.; Mathiot, D.; Claverie, A.
1996-05-01
When end-of-range defects are located close to or within doping profiles they render diffusion "anomalous" by both enhancing the dopant diffusivity and trapping it, both phenomena decreasing with time. Upon annealing, these defects grow in size and their density is reduced through the emission and capture of Si-interstitial atoms by a coarsening process called Ostwald ripening. In this paper, we report on how, by coupling the Ostwald ripening theory with TEM observations of the time evolution of the dislocation loops upon annealing, quantitative information allowing the enhanced diffusivity to be understood can be extracted. Indeed, during the coarsening process, a supersaturation, {C}/{C e}, of Si self-interstitial atoms is maintained between the loops and decreases with time. The enhanced diffusivity is assumed to be linked to the evolution of this interstitial supersaturation during annealing through the interstitial component of boron diffusion. We show that C drastically decreases during the first second of the anneal to asymptotically reach a value just above the equilibrium concentration Ce. This rapid decay is precisely at the origin of the transient enhanced diffusivity of dopants in the vicinity of the loops.
Interstitial pneumonitis after acetylene welding: a case report.
Brvar, Miran
2014-01-01
Acetylene is a colorless gas commonly used for welding. It acts mainly as a simple asphyxiant. In this paper, however, we present a patient who developed a severe interstitial pneumonitis after acetylene exposure during aluminum welding. A 44-year old man was welding with acetylene, argon and aluminum electrode sticks in a non-ventilated aluminum tank for 2 h. Four hours after welding dyspnea appeared and 22 h later he was admitted at the Emergency Department due to severe respiratory insufficiency with pO2 = 6.7 kPa. Chest X-ray showed diffuse interstitial infiltration. Pulmonary function and gas diffusion tests revealed a severe restriction (55% of predictive volume) and impaired diffusion capacity (47% of predicted capacity). Toxic interstitial pneumonitis was diagnosed and high-dose systemic corticosteroid methylprednisolone and inhalatory corticosteroid fluticasone therapy was started. Computed Tomography (CT) of the lungs showed a diffuse patchy ground-glass opacity with no signs of small airway disease associated with interstitial pneumonitis. Corticosteroid therapy was continued for the next 8 weeks gradually reducing the doses. The patient's follow-up did not show any deterioration of respiratory function. In conclusion, acetylene welding might result in severe toxic interstitial pneumonitis that improves after an early systemic and inhalatory corticosteroid therapy.
Tomographic findings of acute pulmonary toxoplasmosis in immunocompetent patients.
de Souza Giassi, Karina; Costa, Andre Nathan; Apanavicius, Andre; Teixeira, Fernando Bin; Fernandes, Caio Julio Cesar; Helito, Alfredo Salim; Kairalla, Ronaldo Adib
2014-11-25
Toxoplasmosis is one of the most common human zoonosis, and is generally benign in most of the individuals. Pulmonary involvement is common in immunocompromised subjects, but very rare in immunocompetents and there are scarce reports of tomographic findings in the literature. The aim of the study is to describe three immunocompetent patients diagnosed with acute pulmonary toxoplasmosis and their respective thoracic tomographic findings. Acute toxoplasmosis was diagnosed according to the results of serological tests suggestive of recent primary infection and the absence of an alternative etiology. From 2009 to 2013, three patients were diagnosed with acute respiratory failure secondary to acute toxoplasmosis. The patients were two female and one male, and were 38, 56 and 36 years old. Similarly they presented a two-week febrile illness and progressive dyspnea before admission. Laboratory tests demonstrated lymphocytosis, slight changes in liver enzymes and high inflammatory markers. Tomographic findings were bilateral smooth septal and peribronchovascular thickening (100%), ground-glass opacities (100%), atelectasis (33%), random nodules (33%), lymph node enlargement (33%) and pleural effusion (66%). All the patients improved their symptoms after treatment, and complete resolution of tomographic findings were found in the followup. These cases provide a unique description of the presentation and evolution of pulmonary tomographic manifestations of toxoplasmosis in immunocompetent patients. Toxoplasma pneumonia manifests with fever, dyspnea and a non-productive cough that may result in respiratory failure. In animal models, changes were described as interstitial pneumonitis with focal infiltrates of neutrophils that can finally evolve into a pattern of diffuse alveolar damage with focal necrosis. The tomographic findings are characterized as ground glass opacities, smooth septal and marked peribronchovascular thickening; and may mimic pulmonary congestion, lymphangitis, atypical pneumonia and pneumocystosis. This is the largest series of CT findings of acute toxoplasmosis in immunocompetent hosts, and the diagnosis should be considered as patients that present with acute respiratory failure in the context of a subacute febrile illness with bilateral and diffuse interstitial infiltrates with marked peribronchovascular thickening. If promptly treated, pulmonary toxoplasmosis can result in complete clinical and radiological recovery in immunocompetent hosts.
Symmetry and diffusivity of the interstitial hydrogen shallow-donor center in In 2O 3
Weiser, Philip; Qin, Ying; Yin, Weikai; ...
2016-11-16
Uniaxial stress experiments performed for the 3306 cm -1 vibrational line assigned to the interstitial-hydrogen, shallow-donor center in In 2O 3 reveal its symmetry and transition- moment direction. The defect alignment that can be produced by a [001] stress applied at 165 K is due to a process that is also a hydrogen- diffusion jump, providing a microscopic determination of the diffusion constant for H in In 2O 3 and its mechanism. Lastly, our experimental results strongly complement theoretical predictions for the structure and diffusion of the interstitial hydrogen donor center in In 2O 3.
Doyle, Tracy J; Dhillon, Namrata; Madan, Rachna; Cabral, Fernanda; Fletcher, Elaine A; Koontz, Diane C; Aggarwal, Rohit; Osorio, Juan C; Rosas, Ivan O; Oddis, Chester V; Dellaripa, Paul F
2018-06-01
To assess clinical outcomes including imaging findings on computed tomography (CT), pulmonary function testing (PFT), and glucocorticoid (GC) use in patients with the antisynthetase syndrome (AS) and interstitial lung disease (ILD) treated with rituximab (RTX). We retrospectively identified all patients at 2 institutions with AS-ILD who were treated with RTX. Baseline demographics, PFT, and chest CT were assessed before and after RTX. Two radiologists independently evaluated CT using a standardized scoring system. Twenty-five subjects at the Brigham and Women's Hospital (n = 13) and University of Pittsburgh Medical Center (n = 12) were included. Antisynthetase antibodies were identified in all patients (16 Jo1, 6 PL-12, 3 PL-7). In 21 cases (84%), the principal indication for RTX use was recurrent or progressive ILD, owing to failure of other agents. Comparing pre- and post-RTX pulmonary variables at 12 months, CT score and forced vital capacity were stable or improved in 88% and 79% of subjects, respectively. Total lung capacity (%) increased from 56 ± 13 to 64 ± 13 and GC dose decreased from 18 ± 9 to 12 ± 12 mg/day. Although DLCO (%) declined slightly at 1 year, it increased from 42 ± 17 to 70 ± 20 at 3 years. The most common imaging patterns on CT were nonspecific interstitial pneumonia (NSIP; n = 13) and usual interstitial pneumonia/fibrotic NSIP (n = 5), of which 5 had concurrent elements of cryptogenic organizing pneumonia. Stability or improvement in pulmonary function or severity of ILD on CT was seen in most patients. Use of RTX was well tolerated in the majority of patients. RTX may play a therapeutic role in patients with AS-ILD, and further clinical investigation is warranted.
Morais, António; Beltrão, Marília; Sokhatska, Oksana; Costa, Diogo; Melo, Natalia; Mota, Patricia; Marques, Agostinho; Delgado, Luís
2015-08-01
Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) has important therapeutic and prognostic implications and would be greatly aided by reliable diagnostic biomarkers as IPF has sometimes overlapping features with other interstitial lung diseases (ILD). To explore the value of serum metalloproteinases (MMP) 1 and 7 levels in the differential diagnosis of IPF with other ILD. MMP-1/7 serum levels were measured using Luminex xMAP technology in 139 patients- 47 IPF, 36 non-IPF Usual Interstitial Pneumonia (UIP), 14 idiopathic Nonspecific Interstitial Pneumonia (iNSIP), 29 secondary NSIP (secNSIP), 13 stage IV sarcoidosis- and 20 healthy controls, and compared using the Mann-Whitney U test. MMP-1 was significantly higher in IPF than non-IPF UIP (P = .042) and sarcoidosis (P = .027). MMP-7 was significantly higher in IPF than controls (P < .001), non-IPF UIP (P = .003), secNSIP (P < .001), and sarcoidosis (P < .001). The Area Under the Curve for IPF versus other ILD was 0.63 (95%CI, 0.53-0.73) for MMP-1, 0.73 (95%CI, 0.65-0.81) for MMP-7, and 0.74 (95%CI, 0.66-0.82) for MMP-1/MMP-7 combined. Sensitivity and specificity for MMP-7 cutoff = 3.91 ng/mL was 72.3% and 66.3%, respectively, Positive Predictive Values = 52.3% and Negative Predictive Values = 82.4%. MMP-1 and particularly MMP-7 serum levels were significantly higher in IPF than in non-IPF UIP, the main entity in differential diagnosis. The value of these biomarkers as additional tools in a multidisciplinary approach to IPF diagnosis needs to be considered and further explored. Copyright © 2015 Elsevier Ltd. All rights reserved.
Pulmonary Function and Survival in Idiopathic vs Secondary Usual Interstitial Pneumonia
Strand, Matthew J.; Sprunger, David; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Frankel, Stephen K.; Huie, Tristan J.; Olson, Amy L.; Solomon, Joshua; Brown, Kevin K.
2014-01-01
BACKGROUND: The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS: We used longitudinal data analytic models to compare groups (IPF [n = 321] and CTD-UIP [n = 56]) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco %), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS: There were no significant differences between groups in longitudinal changes in FVC % or Dlco % up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year [95% CI] was 4.1 [3.4, 4.9] for IPF and 3.5 [1.8, 5.1] for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco % per year was 4.7 [4.0, 5.3] for IPF and 4.3 [3.0, 5.6] for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS: Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF. PMID:24700149
DOE Office of Scientific and Technical Information (OSTI.GOV)
Whinnery, J.E.; Young, J.T.
Albumin lung-scanning agents have a proven high degree of safety, with the only contraindication to their use being allergic hypersensitivity. We have used these agents to investigate the physiologic effects of high G/sub z/ acceleratory forces on pulmonary perfusion using the miniature swine. Multiple doses of human macroaggregated albumin and human-albumin microspheres were given to a miniature swine at various levels of centrifugal acceleration over a 6-wk period. The dosages given were the same per kilogram as those used for routine clinical human studies. The animal subsequently died from a severe granulomatous interstitial pneumonia. The granulomatous lesions suggest that themore » pathogenesis may have involved a cell-mediated delayed hypersensitivity. This interstitial pneumonia may represent the end point in a chronic hypersensitivity response to the human-albumin lung-scanning agents.« less
Tanaka, N; Kunihiro, Y; Kubo, M; Kawano, R; Oishi, K; Ueda, K; Gondo, T
2018-05-29
To identify characteristic high-resolution computed tomography (CT) findings for individual collagen vascular disease (CVD)-related interstitial pneumonias (IPs). The HRCT findings of 187 patients with CVD, including 55 patients with rheumatoid arthritis (RA), 50 with systemic sclerosis (SSc), 46 with polymyositis/dermatomyositis (PM/DM), 15 with mixed connective tissue disease, 11 with primary Sjögren's syndrome, and 10 with systemic lupus erythematosus, were evaluated. Lung parenchymal abnormalities were compared among CVDs using χ 2 test, Kruskal-Wallis test, and multiple logistic regression analysis. A CT-pathology correlation was performed in 23 patients. In RA-IP, honeycombing was identified as the significant indicator based on multiple logistic regression analyses. Traction bronchiectasis (81.8%) was further identified as the most frequent finding based on χ 2 test. In SSc IP, lymph node enlargement and oesophageal dilatation were identified as the indicators based on multiple logistic regression analyses, and ground-glass opacity (GGO) was the most extensive based on Kruskal-Wallis test, which reflects the higher frequency of the pathological nonspecific interstitial pneumonia (NSIP) pattern present in the CT-pathology correlation. In PM/DM IP, airspace consolidation and the absence of honeycombing were identified as the indicators based on multiple logistic regression analyses, and predominance of consolidation over GGO (32.6%) and predominant subpleural distribution of GGO/consolidation (41.3%) were further identified as the most frequent findings based on χ 2 test, which reflects the higher frequency of the pathological NSIP and/or the organising pneumonia patterns present in the CT-pathology correlation. Several characteristic high-resolution CT findings with utility for estimating underlying CVD were identified. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
... called Familial Pulmonary Fibrosis (FPF) or Familial Interstitial Pneumonia (FIP). The most common definition of FPF is two or more primary biological family members (parent, child, or sibling) with the diagnosis of IPF or ...
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive
Newton, Chad A.; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S.; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R.; Garcia, Christine Kim
2017-01-01
Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals. 115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed. Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year−1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis. Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. PMID:27540018
Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive.
Newton, Chad A; Batra, Kiran; Torrealba, Jose; Kozlitina, Julia; Glazer, Craig S; Aravena, Carlos; Meyer, Keith; Raghu, Ganesh; Collard, Harold R; Garcia, Christine Kim
2016-12-01
Heterozygous mutations in four telomere-related genes have been linked to pulmonary fibrosis, but little is known about similarities or differences of affected individuals.115 patients with mutations in telomerase reverse transcriptase (TERT) (n=75), telomerase RNA component (TERC) (n=7), regulator of telomere elongation helicase 1 (RTEL1) (n=14) and poly(A)-specific ribonuclease (PARN) (n=19) were identified and clinical data were analysed.Approximately one-half (46%) had a multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF); others had unclassifiable lung fibrosis (20%), chronic hypersensitivity pneumonitis (12%), pleuroparenchymal fibroelastosis (10%), interstitial pneumonia with autoimmune features (7%), an idiopathic interstitial pneumonia (4%) and connective tissue disease-related interstitial fibrosis (3%). Discordant interstitial lung disease diagnoses were found in affected individuals from 80% of families. Patients with TERC mutations were diagnosed at an earlier age than those with PARN mutations (51±11 years versus 64±8 years; p=0.03) and had a higher incidence of haematological comorbidities. The mean rate of forced vital capacity decline was 300 mL·year -1 and the median time to death or transplant was 2.87 years. There was no significant difference in time to death or transplant for patients across gene mutation groups or for patients with a diagnosis of IPF versus a non-IPF diagnosis.Genetic mutations in telomere related genes lead to a variety of interstitial lung disease (ILD) diagnoses that are universally progressive. Copyright ©ERS 2016.
An integrated approach in the diagnosis of smoking-related interstitial lung diseases.
Caminati, Antonella; Cavazza, Alberto; Sverzellati, Nicola; Harari, Sergio
2012-09-01
Cigarette smoke consists of several chemical compounds with a variety of effects in many organs. In the lung, apart being the main cause of chronic obstructive pulmonary disease, carcinoma and idiopathic spontaneous pneumothorax, tobacco smoke is associated with interstitial lung diseases (ILDs), including respiratory bronchiolitis-associated ILD (RB-ILD), desquamative interstitial pneumonia (DIP), pulmonary Langerhans' cell histiocytosis (PLCH), idiopathic pulmonary fibrosis, acute eosinophilic pneumonia, ILD in rheumatoid arthritis and pulmonary haemorrhage in Goodpasture syndrome. This review will focus on the diseases with a stronger epidemiological association with tobacco smoke, namely RB-ILD, DIP and PLCH. Although the exact pathogenetic evidence linking smoking with these disorders is still not completely understood, there is growing evidence that tobacco smoke targets the terminal or respiratory bronchioles in these diseases, and the differences are reflective of the degree of severity of small airway and parenchymal reaction to the smoke exposure. Despite considerable clinical, radiological and histological overlap between RB-ILD, DIP and PLCH, it is useful to retain the separate classifications for prognostic and therapeutic implications.
Early interstitial lung disease in microscopic polyangiitis: Case report and literature review.
García-Nava, Marcos; Mateos-Toledo, Heidegger; Guevara-Canseco, Ana Patricia Georgina; Infante-González, Cesar Eduardo; Reyes-Nava, Diego Alberto; Estrada-Castro, Emilio
Microscopic polyangiitis (MPA) is a systemic disease included in the Chapel Hill 2012 Classification as necrotizing vasculitis affecting capillaries, venules and arterioles. It usually expresses antineutrophil cytoplasmic antibodies (ANCA) and has a perinuclear immunofluorescence pattern and correlation with anti-myeloperoxidase (MPO) antibodies. Capillaritis with alveolar hemorrhage is the most common manifestation of lung disease. Interstitial lung disease (ILD) is uncommon, with usual interstitial pneumonia being the predominant pattern. However, other patterns such as organizing pneumonia have been described. No guidelines exist for treating patients with ILD and, currently, ANCA-associated vasculitis (AAV) is managed along the lines of small vessel vasculitis. The prognosis with this association is uncertain, with possibilities of relapse and a fatal outcome. We present a case in which ILD was the first manifestation of MPA, without alveolar hemorrhage, with subsequent renal involvement and, in which, the established treatment produced a significant clinical improvement. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.
Vyshedskiy, Andrey; Ishikawa, Sadamu; Murphy, Raymond L H
2011-06-01
To determine the variability of crackle pitch and crackle rate during a single automated-auscultation session with a computerized 16-channel lung-sound analyzer. Forty-nine patients with pneumonia, 52 with congestive heart failure (CHF), and 18 with interstitial pulmonary fibrosis (IPF) performed breathing maneuvers in the following sequence: normal breathing, deep breathing, cough several times; deep breathing, vital-capacity maneuver, and deep breathing. From the auscultation recordings we measured the crackle pitch and crackle rate. Crackle pitch variability, expressed as a percentage of the average crackle pitch, was small in all patients and in all maneuvers: pneumonia 11%, CHF 11%, pulmonary fibrosis 7%. Crackle rate variability was also small: pneumonia 31%, CHF 32%, IPF 24%. Compared to the first deep-breathing maneuver (100%), the average crackle pitch did not significantly change following coughing (pneumonia 100%, CHF 103%, IPF 100%), the vital-capacity maneuver (pneumonia 100%, CHF 92%, IPF 104%), or during quiet breathing (pneumonia 97%, CHF 100%, IPF 104%). Similarly, the average crackle rate did not change significantly following coughing (pneumonia 105%, CHF 110%, IPF 90%) or the vital-capacity maneuver (pneumonia 102%, CHF 101%, IPF 99%). However, during normal breathing the crackle rate was significantly lower in the patients with pneumonia (74%, P < .001) and significantly higher in the patients with IPF (147%, P < .05) than it was during deep breathing. In patients with CHF the average crackle rate during normal breathing was not significantly different from that during the first deep-breathing maneuver (108%). Crackle pitch and rate were surprisingly stable in all 3 conditions. Neither crackle pitch nor crackle rate changed significantly from breath to breath or from one deep-breathing maneuver to another, even when the maneuvers were separated by cough or the vital-capacity maneuver. The observation that crackle rate is a reproducible measurement during one automated-auscultation session suggests that crackle rate can be used to follow the course of cardiopulmonary illnesses such as pneumonia, IPF, and CHF.
Extreme Tetralogy of Fallot With Polycythemia in a Ferret (Mustela putorius furo).
Dias, Sara; Planellas, Marta; Canturri, Albert; Martorell, Jaume
2017-06-01
A 5-month-old, intact male ferret (Mustela putorius furo) was presented with apathy, tachypnea and exercise intolerance. On initial physical examination, tachypnea and cyanosis were the two primary clinical signs detected. The complete blood count also revealed a severe polycythemia, with lymphopenia, neutrophilia and eosinophilia. Further diagnostic imaging tests were performed. The thoracic radiographs revealed cardiomegaly and a diffuse alveolar pulmonary pattern. Consequently, an echocardiography was performed and showed an interventricular septal defect, pulmonic artery occlusion, overriding of the aorta and right ventricle hypertrophy. All abnormalities were compatible with a tetralogy of Fallot (TOF). As a treatment plan, a phlebotomy was performed and the ferret was posteriorly maintained with oxygen and fluid therapy. The following day, the hematocrit decreased 11% and the respiratory distress improved. Four days later, the ferret got clinically worse and was euthanized. A necropsy was performed and confirmed the presence of an extreme TOF with a diffused interstitial pneumonia secondary to Pneumocystis carinii. To the author's knowledge, this is the first report of an extreme tetralogy of Fallot with polycythemia in a ferret. Copyright © 2017 Elsevier Inc. All rights reserved.
Oxygen transport in off-stoichiometric uranium dioxide mediated by defect clustering dynamics
Yu, Jianguo; Bai, Xian -Ming; El-Azab, Anter; ...
2015-03-05
In this study, oxygen transport is central to many properties of oxides such as stoichiometric changes, phase transformation and ionic conductivity. In this paper, we report a mechanism for oxygen transport in uranium dioxide (UO 2) in which the kinetics is mediated by defect clustering dynamics. In particular, the kinetic Monte Carlo (KMC) method has been used to investigate the kinetics of oxygen transport in UO 2 under the condition of creation and annihilation of oxygen vacancies and interstitials as well as oxygen interstitial clustering, with variable offstoichiometry and temperature conditions. It is found that in hypo-stoichiometric UO 2-x, oxygenmore » transport is well described by the vacancy diffusion mechanism while in hyper-stoichiometric UO 2+x, oxygen interstitial cluster diffusion contributes significantly to oxygen transport kinetics, particularly at high temperatures and high off-stoichiometry levels. It is also found that diinterstitial clusters and single interstitials play dominant roles in oxygen diffusion while other larger clusters have negligible contributions. However, the formation, coalescence and dissociation of these larger clusters indirectly affects the overall oxygen diffusion due to their interactions with mono and di-interstitials, thus providing a explanation of the experimental observation of saturation or even drop of oxygen diffusivity at high off-stoichiometry.« less
Dissociative diffusion mechanism in vacancy-rich materials according to mass action kinetics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Biderman, N. J.; Sundaramoorthy, R.; Haldar, Pradeep
We conducted two sets of diffusion-reaction numerical simulations using a finite difference method (FDM) in order to investigate fast impurity diffusion via interstitial sites in vacancy-rich materials such as Cu(In,Ga)Se 2 (CIGS) and Cu 2ZnSn(S, Se) 4 (CZTSSe or CZTS) via the dissociative diffusion mechanism where the interstitial diffuser ultimately reacts with a vacancy to produce a substitutional. The first set of simulations extends the standard interstitial-limited dissociative diffusion theory to vacancy-rich material conditions where vacancies are annihilated in large amounts, introducing non-equilibrium vacancy concentration profiles. The second simulation set explores the vacancy-limited dissociative diffusion where impurity incorporation increases themore » equilibrium vacancy concentration. In addition to diffusion profiles of varying concentrations and shapes that were obtained in all simulations, some of the profiles can be fitted with the constant- and limited-source solutions of Fick’s second law despite the non-equilibrium condition induced by the interstitial-vacancy reaction. The first set of simulations reveals that the dissociative diffusion coefficient in vacancy-rich materials is inversely proportional to the initial vacancy concentration. In the second set of numerical simulations, impurity-induced changes in the vacancy concentration lead to distinctive diffusion profile shapes. The simulation results are also compared with published data of impurity diffusion in CIGS. And according to the characteristic properties of diffusion profiles from the two set of simulations, experimental detection of the dissociative diffusion mechanism in vacancy-rich materials may be possible.« less
Dissociative diffusion mechanism in vacancy-rich materials according to mass action kinetics
Biderman, N. J.; Sundaramoorthy, R.; Haldar, Pradeep; ...
2016-05-13
We conducted two sets of diffusion-reaction numerical simulations using a finite difference method (FDM) in order to investigate fast impurity diffusion via interstitial sites in vacancy-rich materials such as Cu(In,Ga)Se 2 (CIGS) and Cu 2ZnSn(S, Se) 4 (CZTSSe or CZTS) via the dissociative diffusion mechanism where the interstitial diffuser ultimately reacts with a vacancy to produce a substitutional. The first set of simulations extends the standard interstitial-limited dissociative diffusion theory to vacancy-rich material conditions where vacancies are annihilated in large amounts, introducing non-equilibrium vacancy concentration profiles. The second simulation set explores the vacancy-limited dissociative diffusion where impurity incorporation increases themore » equilibrium vacancy concentration. In addition to diffusion profiles of varying concentrations and shapes that were obtained in all simulations, some of the profiles can be fitted with the constant- and limited-source solutions of Fick’s second law despite the non-equilibrium condition induced by the interstitial-vacancy reaction. The first set of simulations reveals that the dissociative diffusion coefficient in vacancy-rich materials is inversely proportional to the initial vacancy concentration. In the second set of numerical simulations, impurity-induced changes in the vacancy concentration lead to distinctive diffusion profile shapes. The simulation results are also compared with published data of impurity diffusion in CIGS. And according to the characteristic properties of diffusion profiles from the two set of simulations, experimental detection of the dissociative diffusion mechanism in vacancy-rich materials may be possible.« less
Rare Variants in RTEL1 Are Associated with Familial Interstitial Pneumonia
Cogan, Joy D.; Zhao, Min; Mitchell, Daphne B.; Rives, Lynette; Markin, Cheryl; Garnett, Errine T.; Montgomery, Keri H.; Mason, Wendi R.; McKean, David F.; Powers, Julia; Murphy, Elissa; Olson, Lana M.; Choi, Leena; Cheng, Dong-Sheng; Blue, Elizabeth Marchani; Young, Lisa R.; Lancaster, Lisa H.; Steele, Mark P.; Brown, Kevin K.; Schwarz, Marvin I.; Fingerlin, Tasha E.; Schwartz, David A.; Lawson, William E.; Loyd, James E.; Zhao, Zhongming; Phillips, John A.; Blackwell, Timothy S.
2015-01-01
Rationale: Up to 20% of cases of idiopathic interstitial pneumonia cluster in families, comprising the syndrome of familial interstitial pneumonia (FIP); however, the genetic basis of FIP remains uncertain in most families. Objectives: To determine if new disease-causing rare genetic variants could be identified using whole-exome sequencing of affected members from FIP families, providing additional insights into disease pathogenesis. Methods: Affected subjects from 25 kindreds were selected from an ongoing FIP registry for whole-exome sequencing from genomic DNA. Candidate rare variants were confirmed by Sanger sequencing, and cosegregation analysis was performed in families, followed by additional sequencing of affected individuals from another 163 kindreds. Measurements and Main Results: We identified a potentially damaging rare variant in the gene encoding for regulator of telomere elongation helicase 1 (RTEL1) that segregated with disease and was associated with very short telomeres in peripheral blood mononuclear cells in 1 of 25 families in our original whole-exome sequencing cohort. Evaluation of affected individuals in 163 additional kindreds revealed another eight families (4.7%) with heterozygous rare variants in RTEL1 that segregated with clinical FIP. Probands and unaffected carriers of these rare variants had short telomeres (<10% for age) in peripheral blood mononuclear cells and increased T-circle formation, suggesting impaired RTEL1 function. Conclusions: Rare loss-of-function variants in RTEL1 represent a newly defined genetic predisposition for FIP, supporting the importance of telomere-related pathways in pulmonary fibrosis. PMID:25607374
Park, Silvia; Kang, Cheol-In; Chung, Doo Ryeon; Peck, Kyong Ran; Kim, Won Seog; Kim, Seok Jin
2015-07-01
Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard chemotherapy in diffuse large B-cell lymphoma (DLBCL) patients. Although febrile neutropenia (FN) is the major toxicity of this regimen, non-neutropenic fever (NNF) becomes an emerging issue. We analyzed clinical features and outcomes of febrile complications from 397 patients with newly diagnosed DLBCL who were registered in the prospective cohort study. They had completed R-CHOP between September 2008 and January 2013. Thirty-nine patients (9.8%) had NNF whereas 160 patients (40.3%) had FN. Among them, 24 patients (6.0%) had both during their treatment. Compared to frequent occurrence of initial FN after the first cycle (> 50% of total events), more than 80% of NNF cases occurred after the third cycle. Interstitial pneumonitis comprised the highest proportion of NNF cases (54.8%), although the causative organism was not identified in the majority of cases. Thus, pathogen was identified in a limited number of patients (n=9), and Pneumocystis jiroveci pneumonia (PJP) was the most common. Considering that interstitial pneumonitis without documented pathogen could be clinically diagnosed with PJP, the overall rate of PJP including probable cases was 4.5% (18 cases from 397 patients). The NNF-related mortality rate was 10.3% (four deaths from 39 patients with NNF) while the FN-related mortality rate was only 1.3%. NNF was observed with incidence of 10% during R-CHOP treatment, and showed different clinical manifestations with respect to the time of initial episode and causes.
NASA Technical Reports Server (NTRS)
Kitabatake, M.; Fons, P.; Greene, J. E.
1991-01-01
The relaxation, diffusion, and annihilation of split and hexagonal interstitials resulting from 10 eV Si irradiation of (2x1)-terminated Si(100) are investigated. Molecular dynamics and quasidynamics simulations, utilizing the Tersoff many-body potential are used in the investigation. The interstitials are created in layers two through six, and stable atomic configurations and total potential energies are derived as a function of site symmetry and layer depth. The interstitial Si atoms are allowed to diffuse, and the total potential energy changes are calculated. Lattice configurations along each path, as well as the starting configurations, are relaxed, and minimum energy diffusion paths are derived. The results show that the minimum energy paths are toward the surface and generally involved tetrahedral sites. The calculated interstitial migration activation energies are always less than 1.4 eV and are much lower in the near-surface region than in the bulk.
Kinetics of self-interstitial migration in bcc and fcc transition metals
NASA Astrophysics Data System (ADS)
Bukkuru, S.; Bhardwaj, U.; Srinivasa Rao, K.; Rao, A. D. P.; Warrier, M.; Valsakumar, M. C.
2018-03-01
Radiation damage is a multi-scale phenomenon. A thorough understanding of diffusivities and the migration energies of defects is a pre-requisite to quantify the after-effects of irradiation. We investigate the thermally activated mobility of self-interstitial atom (SIA) in bcc transition metals Fe, Mo, Nb and fcc transition metals Ag, Cu, Ni, Pt using molecular dynamics (MD) simulations. The self-interstitial diffusion involves various mechanisms such as interstitialcy, dumbbell or crowdion mechanisms. Max-Space Clustering (MSC) method has been employed to identify the interstitial and its configuration over a wide range of temperature. The self-interstitial diffusion is Arrhenius like, however, there is a slight deviation at high temperatures. The migration energies, pre-exponential factors of diffusion and jump-correlation factors, obtained from these simulations can be used as inputs to Monte Carlo simulations of defect transport. The jump-correlation factor shows the degree of preference of rectilinear or rotational jumps. We obtain the average jump-correlation factor of 1.4 for bcc metals and 0.44 for fcc metals. It indicates that rectilinear jumps are preferred in bcc metals and rotational jumps are preferred in fcc metals.
The lung in rheumatoid arthritis - focus on interstitial lung disease.
Spagnolo, Paolo; Lee, Joyce C; Sverzellati, Nicola; Rossi, Giulio; Cottin, Vincent
2018-05-27
Interstitial lung disease (ILD) is an increasingly recognized complication of rheumatoid arthritis (RA) and is associated with significant morbidity and mortality. In addition, approximately one-third of patients have subclinical disease with varying degrees of functional impairment. While risk factors for RA-ILD are well established (e.g., older age, male gender, ever smoking history and seropositivity to rheumatoid factor and anti-cyclic citrullinated peptide antibodies) little is known about optimal disease assessment, treatment and monitoring, particularly in patients with progressive disease. Patients with RA-ILD are also at high risk of infection and drug toxicity, which, along with comorbidities, complicate further treatment decision making. There are distinct histopathologic patterns of RA-ILD with different clinical phenotypes, natural history and prognosis. Of these, the usual interstitial pneumonia (UIP) subtype of RA-ILD shares a number of clinical and histopathologic features with idiopathic pulmonary fibrosis (IPF), the most common and severe of the idiopathic interstitial pneumonias, suggesting the existence of common mechanistic pathways and possibly therapeutic targets. There remain substantial gaps in our knowledge of RA-ILD. Concerted multinational effort of expert centres has the potential to elucidate the basic mechanisms underlying RA-UIP and other subtypes of RA-ILD and facilitate the development of more efficacious and safer drugs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Boron diffusion in bcc-Fe studied by first-principles calculations
NASA Astrophysics Data System (ADS)
Xianglong, Li; Ping, Wu; Ruijie, Yang; Dan, Yan; Sen, Chen; Shiping, Zhang; Ning, Chen
2016-03-01
The diffusion mechanism of boron in bcc-Fe has been studied by first-principles calculations. The diffusion coefficients of the interstitial mechanism, the B-monovacancy complex mechanism, and the B-divacancy complex mechanism have been calculated. The calculated diffusion coefficient of the interstitial mechanism is D0 = 1.05 × 10-7 exp (-0.75 eV/kT) m2 · s-1, while the diffusion coefficients of the B-monovacancy and the B-divacancy complex mechanisms are D1 = 1.22 × 10-6 f1 exp (-2.27 eV/kT) m2 · s-1 and D2 ≈ 8.36 × 10-6 exp (-4.81 eV/kT) m2 · s-1, respectively. The results indicate that the dominant diffusion mechanism in bcc-Fe is the interstitial mechanism through an octahedral interstitial site instead of the complex mechanism. The calculated diffusion coefficient is in accordance with the reported experiment results measured in Fe-3%Si-B alloy (bcc structure). Since the non-equilibrium segregation of boron is based on the diffusion of the complexes as suggested by the theory, our calculation reasonably explains why the non-equilibrium segregation of boron is not observed in bcc-Fe in experiments. Project supported by the National Natural Science Foundation of China (Grant No. 51276016) and the National Basic Research Program of China (Grant No. 2012CB720406).
Formation and Migration Energies of Interstitials in Silicon Under Strain Conditions
NASA Technical Reports Server (NTRS)
Halicioglu, Timur; Barnett, David M.
1999-01-01
Simulation calculations are conducted for Si substrates to analyze formation and diffusion energies of interstitials under strain condition using statics methods .based on a Stillinger-Weber type potential function. Defects in the vicinity of the surface region and in the bulk are examined, and the role played by compressive and tensile strains on the energetics of interstitials is investigated. Results indicate that strain alters defect energetics which, in turn, modifies their diffusion characteristics.
Yamanda, Shinsuke; Kobayashi, Seiichi; Hanagama, Masakazu; Sato, Hikari; Suzuki, Satoshi; Ueda, Shinsaku; Takahashi, Toru; Yanai, Masaru
We report two cases of organizing pneumonia (OP) secondary to the inhalation of the dried tsunami sludge which formed during the 2011 Great East Japan Earthquake and the consequent tsunami. After the disaster, both of these patients had been engaged in the restoration work. About half a month later, they developed shortness of breath and pulmonary infiltrates. These patients were diagnosed with interstitial pneumonia. Their biopsy specimens revealed multifocal peribronchiolitis and OP. An electron probe microanalysis of these specimens demonstrated the presence of elements from the earth's crust in the inflammatory lesions. These two cases indicate that exposure to dried tsunami sludge can cause OP.
CT of chronic infiltrative lung disease: Prevalence of mediastinal lymphadenopathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Niimi, Hiroshi; Kang, Eun-Young; Kwong, S.
1996-03-01
Our goal was to determine the prevalence of mediastinal lymph node enlargement at CT in patients with diffuse infiltrative lung disease. The study was retrospective and included 175 consecutive patients with diffuse infiltrative lung diseases. Diagnoses included idiopathic pulmonary fibrosis (IPF) (n = 61), usual interstitial pneumonia associated with collagen vascular disease (CVD) (n = 20), idiopathic bronchiolitis obliterans organizing pneumonia (BOOP) (n = 22), extrinsic allergic alveolitis (EAA) (n = 17), and sarcoidosis (n = 55). Fifty-eight age-matched patients with CT of the chest performed for unrelated conditions served as controls. The presence, number, and sites of enlarged nodesmore » (short axis {ge}10 mm in diameter) were recorded. Enlarged mediastinal nodes were present in 118 of 175 patients (67%) with infiltrative lung disease and 3 of 58 controls (5%) (p < 0.001). The prevalence of enlarged nodes was 84% (46 of 55) in sarcoidosis, 67% (41 of 61) in IPF, 70% (14 of 20) in CVD, 53% (9 of 17) in EAA, and 36% (8 of 22) in BOOP. The mean number of enlarged nodes was higher in sarcoidosis (mean 3.2) than in the other infiltrative diseases (mean 1.2) (p < 0.001). Enlarged nodes were most commonly present in station 10R, followed by 7, 4R, and 5. Patients with infiltrative lung disease frequently have enlarged mediastinal lymph nodes. However, in diseases other than sarcoid, usually only one or two nodes are enlarged and their maximal short axis diameter is <15 mm. 11 refs., 2 figs., 1 tab.« less
First-principles multiple-barrier diffusion theory. The case study of interstitial diffusion in CdTe
Yang, Ji -Hui; Park, Ji -Sang; Kang, Joongoo; ...
2015-02-17
The diffusion of particles in solid-state materials generally involves several sequential thermal-activation processes. However, presently, diffusion coefficient theory only deals with a single barrier, i.e., it lacks an accurate description to deal with multiple-barrier diffusion. Here, we develop a general diffusion coefficient theory for multiple-barrier diffusion. Using our diffusion theory and first-principles calculated hopping rates for each barrier, we calculate the diffusion coefficients of Cd, Cu, Te, and Cl interstitials in CdTe for their full multiple-barrier diffusion pathways. As a result, we found that the calculated diffusivity agrees well with the experimental measurement, thus justifying our theory, which is generalmore » for many other systems.« less
Toyokura, Minoru; Fujii, Chieko; Urano, Tetsuya; Nishiya, Kenzo; Ishida, Akira
2003-10-01
We reported a patient who developed acute quadriplegic myopathy (AQM) following treatment with a combination of high-dose steroid and nondepolarizing blocking agent for idiopathic interstitial pneumonia (IIP). Few cases of AQM with IIP have been reported in the literature. The HP progressed rapidly in our patient, but the high-dose steroid therapy was effective. The rehabilitative intervention comprised of passive range-of-motion exercise, functional training, and muscle strengthening. After the initial presentation with severe weakness, the AQM gradually improved and the patient regained full physical function in 8 months. The clinical course was almost identical to that of AQM patients with other lung diseases. Though unlikely to influence the improvement of muscle weakness in AQM patients, the lung diseases associated with AQM may require specific consideration in determining suitable rehabilitation programs and observing patients before and after full recovery from dysmobility.
Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo
2018-02-01
Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.
Mlika, Mona; Kasmi, Rihem; Safra, Ines; Braham, Emna; Chebbi, Chokri; Mezni, Faouzi El
2017-10-01
Diffuse interstitial pneumonias are considered as a group of multiple affections characterized by challenging diagnoses because of the lack of specific clinical signs. Radiologic investigations highlight the diagnoses in most of the cases but bronchoalveolar lavage plays a key role in the diagnostic diagram. We aim to compare the immunocytochemical technique and the flow cytometry in the phenotyping of lymphocytic alveolitis. We described a series of 32 lymphocytic alveolitis, which were analyzed using immunocytochemistry and flow cytometry. We found a good reproducibility between the immunocytochemistry performed on smears and cytoblocks (kappa=0.7) and a poor reproducibility between immunocytochemistry and flow cytometry (kappa=0.35). Our study emphasized on the poor reproducibility between immunocytochemistry and flow cytometry. Further studies about the reliability of both techniques are needed especially in discordant cases. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Macrophage migration inhibitory factor in lung tissue of idiopathic pulmonary fibrosis patients.
Olivieri, Carmela; Bargagli, Elena; Inghilleri, Simona; Campo, Ilaria; Cintorino, Marcella; Rottoli, Paola
2016-06-01
Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disorder characterized by a pattern of Usual Interstitial Pneumonia where the presence of fibroblastic foci is the hallmark of the disease. In the present study, we analyzed the migration inhibitory factor (MIF) expression in lung tissue of IPF patients compared with healthy controls and organizing pneumonia (OP) patients focusing into MIF potential role in fibroblastic foci development. The immunohistochemical analysis was performed in 10 IPF patients (7 male), 3 OP patients (2 male), and 3 healthy controls (all male) using the streptavidin-biotin method (Dako). In IPF samples, MIF resulted overexpressed in the areas of active fibrosis and, in particular, in the alveolar epithelium, bronchiolar epithelium, and in the peripheral zones of fibroblastic foci. Bronchiolar epithelium from organizing pneumonia patients resulted only weakly positive for MIF while no evidence of MIF expression was reported for alveolar epithelium. In the control subject group, MIF was unexpressed except for a weak presence in the bronchiolar epithelium. In conclusion, MIF is a pleiotropic cytokine involved in the pathogenesis of IPF being mainly expressed in the areas of remodeling and active fibrosis, in bronchiolar and alveolar epithelium, and in the peripheral zone of fibroblastic foci.
Influence of dislocation strain fields on the diffusion of interstitial iron impurities in silicon
NASA Astrophysics Data System (ADS)
Ziebarth, Benedikt; Mrovec, Matous; Elsässer, Christian; Gumbsch, Peter
2015-09-01
The efficiency of silicon (Si)-based solar cells is strongly affected by crystal defects and impurities. Metallic impurities, in particular interstitial iron (Fe) atoms, cause large electric losses because they act as recombination centers for photogenerated charge carriers. Here, we present a systematic first-principles density functional theory (DFT) study focusing on the influence of hydrostatic, uniaxial, and shear strains on the thermodynamic stability and the diffusivity of Fe impurities in crystalline Si. Our calculations show that the formation energy of neutral Fe interstitials in tetrahedral interstitial sites is almost unaffected by uniform deformations of the Si crystal up to strains of 5%. In contrast, the migration barrier varies significantly with strain, especially for hydrostatic deformation. In order to determine effective diffusion coefficients for different strain states, a kinetic Monte Carlo (kMC) model was set up based on the activation energy barriers and frequency factors obtained from the DFT simulations. By using the strain dependence of the migration barrier, we examined the migration of Fe interstitials in the vicinity of perfect 1 /2 <110 > screw and 60∘ mixed dislocations, and 1 /6 <112 > 90∘ and 30∘ partial dislocations. While the strain field of the perfect screw dislocation always enhances the local Fe diffusion, the existence of tensile and compressive regions around the 60∘ mixed dislocation results in a strong anisotropic diffusion profile with significantly faster and slower diffusivities on its tensile and compressive sides. The influences of the partial dislocations are qualitatively similar to that of the 60∘ mixed dislocation.
Characterization of lymphocyte populations in nonspecific interstitial pneumonia*
Keogh, Karina A; Limper, Andrew H
2005-01-01
Study objectives Nonspecific interstitial pneumonia (NSIP) has been identified as a distinct entity with a more favorable prognosis and better response to immunosuppressive therapies than usual interstitial pneumonia (UIP). However the inflammatory profile of NSIP has not been characterized. Design Using immunohistochemistry techniques on open lung biopsy specimens, the infiltrate in NSIP was characterized in terms of T and B cells, and macrophages, and the T cell population further identified as either CD4 (helper) or CD8 (suppressor-cytotoxic) T cells. The extent of Th1 and Th2 cytokine producing cells was determined and compared to specimens from patients with UIP. Results In ten NSIP tissue samples 41.4 ± 4% of mononuclear cells expressed CD3, 24.7 ± 1.8% CD4, 19.1 ± 2% CD8, 27.4 ± 3.9% CD20, and 14.3 ± 1.6% had CD68 expression. Mononuclear cells expressed INFγ 21.9 ± 1.9% of the time and IL-4 in 3.0 ± 1%. In contrast, biopsies from eight patients with UIP demonstrated substantially less cellular staining for either cytokine (INFγ; 4.6 ± 1.7% and IL-4; 0.6 ± 0.3%). Significant populations of CD20 positive B-cells were also identified. Conclusion The lymphocytic infiltrate in NSIP is characterized by an elevated CD4/CD8 T-cell ratio, and is predominantly of Th1 type, with additional populations rich in B-cells. Such features are consistent with the favorable clinical course observed in patients with NSIP compared to UIP. PMID:16287509
Çakmakçı Karadoğan, Dilek; Balkarlı, Ayşe; Önal, Özgür; Altınışık, Göksel; Çobankara, Veli
2015-01-01
Nailfold capillaroscopy (NFC) is a non-invasive diagnostic test that is mostly used for early diagnosis of collagen tissue diseases (CTDs). We aimed to evaluate whether NFC findings could be a clue for discriminating idiopathic interstitial lung diseases (ILD) from CTD associated ILDs (CTD-ILD). Additionally it was aimed to determine whether NFC could be helpful in discriminating usual interstitial pneumonia (UIP) pattern from non-specific interstitial pneumonia (NSIP) pattern. We grouped patients into three main groups: 15 CTD-ILD, 18 idiopathic ILD, and 17 patients in the control group. The CTD-ILD group was split into two subgroups: 8 patients with Sjögren's syndrome (SJS)-associated ILD and 7 with rheumatoid arthritis (RA)-associated ILD. The idiopathic-ILD group consisted of 10 idiopathic NSIP and 8 IPF patients. The control group consisted of 10 SJS and 7 RA patients without lung disease. None of the patients were on acute exacerbation at the time of examination, and none had Reynaud's phenomenon. Mean capillary density was significantly reduced only in the CTD-ILD group as compared to the control group (p= 0.006). In subgroup analysis, it was determined that RA-ILD, IPF, and SJS-ILD subgroups had more severe capillaroscopic abnormalities. Mean capillary density in patients with the UIP pattern was reduced compared to patients with the NSIP pattern and those in the control group; p values were 0.008 and < 0.001, respectively. This study is to be the first describing and comparing the nailfold capillaroscopic findings of patients with NSIP and UIP patterns. NFC findings can be helpful in discriminating UIP patterns from NSIP patterns. But to show its role in differentiating idiopathic disease, more studies with more patients are needed.
Loxoprofen-induced interstitial pneumonia: a case report.
Kato, Motoyasu; Sasaki, Shinichi; Sekimoto, Yasuhito; Arano, Naoko; Jo, Hitomi; Suina, Kentaro; Kuriyama, Sachiko; Muraki, Keiko; Nagashima, Osamu; Yoshioka, Yasuko; Tominaga, Shigeru; Takahashi, Kazuhisa
2016-05-25
Loxoprofen is a nonsteroidal anti-inflammatory drug used in the treatment of many diseases. However, there are no case reports about loxoprofen-induced pneumonia. We have encountered a rare case of loxoprofen-induced pneumonia. We report the case of a 71-year-old Japanese woman who was initially treated with loxoprofen for fever. She was admitted to our hospital because of worsening of her symptoms, including fever and dyspnea. Her symptoms improved after treatment with ceftriaxone. Seven days after admission, she again developed high fever. She was again treated with loxoprofen and levofloxacin. However, acute respiratory failure developed after initiation of loxoprofen treatment. Chest computed tomography showed peribronchovascular consolidation. She was diagnosed with loxoprofen-induced pneumonia for which she was administered steroids. After treatment, her dyspnea and radiological findings improved. The findings in this case report reveal an association between treatment with a nonsteroidal anti-inflammatory drug and pneumonia. This rare case was diagnosed after accidental retreatment with loxoprofen. This is the first report of loxoprofen-induced pneumonia.
Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases.
Meng, Peng; Tan, Gan Liang; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand
2016-12-01
Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients' final diagnoses based on multi-disciplinary consensus. One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24-79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited.
Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris.
Duchemann, Boris; Annesi-Maesano, Isabella; Jacobe de Naurois, Camille; Sanyal, Shreosi; Brillet, Pierre-Yves; Brauner, Michel; Kambouchner, Marianne; Huynh, Sophie; Naccache, Jean Marc; Borie, Raphael; Piquet, Jacques; Mekinian, Arsène; Virally, Jerôme; Uzunhan, Yurdagul; Cadranel, Jacques; Crestani, Bruno; Fain, Olivier; Lhote, Francois; Dhote, Robin; Saidenberg-Kermanac'h, Nathalie; Rosental, Paul-André; Valeyre, Dominique; Nunes, Hilario
2017-08-01
The objective of the study was to estimate the prevalence and incidence of interstitial lung diseases (ILDs) in Seine-Saint-Denis, a multi-ethnic county of Greater Paris, France.Patients with ILDs were identified between January and December 2012 by using several sources; all potentially involved medical specialists from public and private hospitals, community-based pulmonologists and general practitioners, and the Social Security system. Diagnoses were validated centrally by an expert multidisciplinary discussion.1170 ILD cases were reported (crude overall prevalence: 97.9/10 5 and incidence: 19.4/10 5 /year). In the 848 reviewed cases, the most prevalent diagnoses were sarcoidosis (42.6%), connective tissue diseases associated ILDs (CTDs-ILDs) (16%), idiopathic pulmonary fibrosis (IPF) (11.6%), and occupational ILDs (5.0%), which corresponded to a crude prevalence of 30.2/10 5 for sarcoidosis, 12.1/10 5 for CTDs-ILDs and 8.2/10 5 for IPF. The prevalence of fibrotic idiopathic interstitial pneumonias, merging IPF, nonspecific interstitial pneumonia and cases registered with code J84.1 was 16.34/10 5 An adjusted multinomial model demonstrated an increased risk of sarcoidosis in North Africans and Afro-Caribbeans and of CTDs-ILDs in Afro-Caribbeans, compared to that in Europeans.This study, with a comprehensive recruitment and stringent diagnostic criteria, emphasises the importance of secondary ILDs, particularly CTDs-ILDs and the relatively low prevalence of IPF, and confirms that sarcoidosis is a rare disease in France. Copyright ©ERS 2017.
Effect of nickel on point defects diffusion in Fe – Ni alloys
Anento, Napoleon; Serra, Anna; Osetsky, Yury N.
2017-05-05
Iron-Nickel alloys are perspective alloys as nuclear energy structural materials because of their good radiation damage tolerance and mechanical properties. Understanding of experimentally observed features such as the effect of Ni content to radiation defects evolution is essential for developing predictive models of radiation. Recently an atomic-scale modelling study has revealed one particular mechanism of Ni effect related to the reduced mobility of clusters of interstitial atoms in Fe-Ni alloys. In this paper we present results of the microsecond-scale molecular dynamics study of point defects, i.e. vacancies and self-interstitial atoms, diffusion in Fe-Ni alloys. It is found that the additionmore » of Ni atoms affects diffusion processes: diffusion of vacancies is enhanced in the presence of Ni, whereas diffusion of interstitials is reduced and these effects increase at high Ni concentration and low temperature. As a result, the role of Ni solutes in radiation damage evolution in Fe-Ni alloys is discussed.« less
First-principles study of fission gas incorporation and migration in zirconium nitride
Mei, Zhi-Gang; Liang, Linyun; Yacout, Abdellatif M.
2017-03-24
To evaluate the effectiveness of ZrN as a diffusion barrier against fission gases, we investigate in this paper the incorporation and migration of fission gas atoms, with a focus on Xe, in ZrN by first-principles calculations. The formations of point defects in ZrN, including vacancies, interstitials, divacancies, Frenkel pairs, and Schottky defects, are first studied. Among all the defects, the Schottky defect with two vacancies as first nearest neighbor is predicted to be the most favorable incorporation site for fission gas Xe in ZrN. The migration of Xe gas atom in ZrN is investigated through two diffusion mechanisms, i.e., interstitialmore » and vacancy-assisted diffusions. The migration barrier of Xe gas atom through the intrinsic interstitials in ZrN is considerably lower than that through vacancies. Finally, therefore, at low temperatures fission gas Xe atoms diffuse mainly through interstitials in single crystal ZrN, whereas at high temperatures Xe may diffuse in ZrN assisted by vacancies.« less
Takato, Hazuki; Waseda, Yuko; Watanabe, Satoshi; Inuzuka, Kanako; Katayama, Nobuyuki; Ichikawa, Yukari; Yasui, Masahide; Fujimura, Masaki
2013-01-01
Autoantibodies against aminoacyl-tRNA synthetases (ARS) have been found to be highly specific for polymyositis and dermatomyositis (PM/DM) and to correlate strongly with complicating interstitial pneumonia (IP). The aim of the present study was to compare the clinical presentations of anti-ARS antibody-positive IP patients with or without manifestations of PM/DM. We retrospectively examined 36 IP patients with anti-ARS antibodies. Sixteen patients presented with and 20 without the features of PM/DM. They were divided into PM/DM-IP and idiopathic-IP (IIP) groups. Clinical symptoms, findings on physical examination, laboratory data, pulmonary function, computed tomography (CT), and bronchoalveolar lavage fluid (BALF) cell counts were compared. Skin findings, myalgia, and elevation of serum creatinine kinase were found in the PM/DM-IP group. Features common to both groups included: volume loss in lower bilateral lobes; ground-glass opacities, reticular shadows and traction bronchiectasis on chest CT; high percentage of lymphocytes (IIP: 44.0% ± 21.0% (mean ± SD), PM/DM-IP: 50.5% ± 23.5%) and low CD4/8 ratios (IIP: 0.36 ± 0.34, PM/DM-IP: 0.44 ± 0.42) in BALF; decreased pulmonary function, including percentage of predicted vital capacity (VC) (IIP: 80.1% ± 15.4%, PM/DM-IP: 73.6% ± 16.4%), residual volume (RV) (IIP: 70.7% ± 21.7%, PM/DM-IP: 71.5% ± 17.1%), total lung capacity (TLC) (IIP: 73.4% ± 13.6%, PM/DM-IP: 71.6% ± 13.0%), and diffusing capacity DLco (IIP: 57.5% ± 26.7%, PM/DM-IP: 46.4% ± 10.3%). Both groups achieved good responses to initial corticosteroid or immunosuppressant therapy. Patients with anti-ARS antibody-positive IP have common pulmonary manifestations regardless of the presence of PM/DM. Copyright © 2012. Published by Elsevier Ltd.
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-16
...: Acute kidney injury Acute interstitial pneumonia (re-presentation) Atrial fibrillation Highly calcified... encephalomyelitis Acute necrotizing hemorrhagic encephalopathy Atrial fibrillation and flutter Benign shuddering... resurfacing Lead extraction Left atrial appendage exclusion femoral/epicardial access Neuroflow endovascular...
Khalil, Nasreen; O'Connor, Robert
2004-07-20
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal pulmonary fibrotic lung disease. The diagnostic histological changes are called usual interstitial pneumonia and are characterized by histological temporal heterogeneity, whereby normal lung tissue is interspersed with interstitial fibrosis, honeycomb cysts and fibroblast foci. Pulmonary functions show restricted volumes and capacities, preserved flows and evidence of decreased gas exchange. High-resolution computed axial tomography demonstrates evidence of fibrosis and lung remodelling such as honeycomb cysts and traction bronchiectasis. There is no known effective treatment for IPF, but lung transplantation improves survival.
Jee, Adelle S.; Adelstein, Stephen; Bleasel, Jane; Keir, Gregory J.; Nguyen, MaiAnh; Sahhar, Joanne; Youssef, Peter; Corte, Tamera J.
2017-01-01
The diagnosis of interstitial lung disease (ILD) requires meticulous evaluation for an underlying connective tissue disease (CTD), with major implications for prognosis and management. CTD associated ILD (CTD-ILD) occurs most commonly in the context of an established CTD, but can be the first and/or only manifestation of an occult CTD or occur in patients who have features suggestive of an autoimmune process, but not meeting diagnostic criteria for a defined CTD—recently defined as “interstitial pneumonia with autoimmune features” (IPAF). The detection of specific autoantibodies serves a critical role in the diagnosis of CTD-ILD, but there remains a lack of data to guide clinical practice including which autoantibodies should be tested on initial assessment and when or in whom serial testing should be performed. The implications of detecting autoantibodies in patients with IPAF on disease behaviour and management remain unknown. The evaluation of CTD-ILD is challenging due to the heterogeneity of presentations and types of CTD and ILD that may be encountered, and thus it is imperative that immunologic tests are interpreted in conjunction with a detailed rheumatologic history and examination and multidisciplinary collaboration between respiratory physicians, rheumatologists, immunologists, radiologists and pathologists. PMID:28471413
Biopsy in idiopathic pulmonary fibrosis: back to the future.
Rossi, Giulio; Spagnolo, Paolo
2017-09-01
Idiopathic Pulmonary Fibrosis (IPF) is a relentlessly progressive, fibrosing interstitial pneumonia characterized by a radiologic and/or histologic pattern of usual interstitial pneumonia (UIP). The availability of two effective anti-fibrotic drugs in IPF has encouraged the identification and treatment of patients in early stages in order to maximize clinical benefit. The ability of high-resolution computed tomography (HRCT) to identify a 'definite' UIP pattern is suboptimal, particularly in the absence of honeycombing. Therefore, radiologic criteria for UIP are currently being redefined. Histology represents the major source of information to define a UIP pattern. Novel and less invasive approaches (particularly cryobiopsy) to sample interstitial lung diseases have demonstrated high sensitivity and specificity. In parallel, researchers are focusing on molecular mechanisms underlying IPF with the aim to identify more specific druggable targets. Lung tissue is therefore essential for diagnostic, pathogenetic and therapeutic purposes. Areas covered: We identified and critically reviewed the most relevant recent literature related to the limitations of current radiologic criteria, new lung sampling procedures, and molecular pathways in support of the need of lung tissue to better understand IPF. Expert commentary: The development of truly effective treatments for IPF requires the identification of key pathogenetic molecules and pathways. To this end, the availability of lung tissue is vital.
NASA Astrophysics Data System (ADS)
DSouza, Alisha V.; Marra, Kayla; Gunn, Jason R.; Samkoe, Kimberley S.; Pogue, Brian W.
2016-10-01
Lymphatic uptake of interstitially administered agents occurs by passive convective-diffusive inflow driven by interstitial concentration and pressure, while the downstream lymphatic transport is facilitated by active propulsive contractions of lymphatic vessel walls. Near-infrared fluorescence imaging in mice was used to measure these central components of lymphatic transport for the first time, using two different-sized molecules-methylene blue (MB) and fluorescence-labeled antibody immunoglobulin G (IgG)-IRDye 680RD. This work confirms the hypothesis that lymphatic passive inflow and active propulsion rates can be separated based upon the relative differences in Stokes-Einstein diffusion coefficient. This coefficient specifically affects the passive-diffusive uptake when the interstitial volume and pressure are constant. Parameters such as mean time-to-peak signal, overall fluorescence signal intensities, and number of active peristaltic pulses, were estimated from temporal imaging data. While the mean time to attain peak signal representative of diffusion-dominated flow in the lymph vessels was 0.6±0.2 min for MB and 8±6 min for IgG, showing a size dependence, the active propulsion rates were 3.4±0.8 pulses/min and 3.3±0.5 pulses/min, respectively, appearing size independent. The propulsion rates for both dyes decreased with clearance from the interstitial injection-site, indicating intrinsic control of the smooth muscles in response to interstitial pressure. This approach to size-comparative agent flow imaging of lymphatic function can enable noninvasive characterization of diseases related to uptake and flow in lymph networks.
Barashev, A. V.; Golubov, S. I.; Stoller, R. E.
2015-06-01
We studied the radiation growth of zirconium using a reaction–diffusion model which takes into account intra-cascade clustering of self-interstitial atoms and one-dimensional diffusion of interstitial clusters. The observed dose dependence of strain rates is accounted for by accumulation of sessile dislocation loops during irradiation. Moreover, the computational model developed and fitted to available experimental data is applied to study deformation of Zr single crystals under irradiation up to hundred dpa. Finally, the effect of cold work and the reasons for negative prismatic strains and co-existence of vacancy and interstitial loops are elucidated.
Tomii, Keisuke; Kato, Terufumi; Takahashi, Masashi; Noma, Satoshi; Kobashi, Yoichiro; Enatsu, Sotaro; Okubo, Sumiko; Kobayashi, Noriko; Kudoh, Shoji
2017-04-01
Interstitial lung disease (ILD) is important drug related toxicity because it commonly forced to discontinue the treatment. To characterize the prevalence and patterns of pemetrexed induced ILD, an independent ILD advisory board composed of external experts performed reassessment of ILD in two post marketing surveillance (PMS) studies for malignant pleural mesothelioma (MPM) and non-small cell lung cancer (NSCLC). ILD incidences were originally 1.6% and 2.6% in 903 MPM and 683 NSCLC patients in safety analyses, respectively. Based on the reassessment by the board, the incidence was 1.1% MPM and 1.8% NSCLC. Common possible risk factors of ILD in MPM and NSCLC patients were male gender, 60 years or older age, and pre-existing ILD. Asbestosis in MPM, and smoking history in NSCLC are also considered as risk, respectively. In terms of computed tomography (CT) pattern, 7 of 10 cases in MPM patients had acute interstitial pneumonia pattern, which four were fatal. Eight of the 12 NSCLC patients had diffuse grand glass opacity, which all had recovered. Onset of ILD in MPM varied between the first and the fifth courses of pemetrexed treatment, and the latest onset was 48 days after the last administration. For NSCLC, it was between the second and the ninth course, 7 and 56 days after the last administration. The risk of pemetrexed-related ILD is similar level as other anti-cancer drugs under clinical settings. Careful observations continuously during and at least for 2 months after the last administration of pemetrexed are advised. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Pneumocystis jirovecii infection in patients with acute interstitial pneumonia.
Martínez-Rísquez, M T; Friaza, V; de la Horra, C; Martín-Juan, J; Calderón, E J; Medrano, F J
2018-06-08
Acute interstitial pneumonia (AIP) is a severe disease of unknown etiology. Pneumocystis jirovecii is an atypical opportunistic fungus able to colonize patients with chronic pulmonary disease and inducing alveolar macrophage activation. The aim of this study was to evaluate the possible association between Pneumocystis jirovecii and AIP. The presence of P. jirovecii in bronchoalveolar lavage fluid in the four confirmed cases of AIP identified in a tertiary-care hospital over a period of nine years was studied using a 2-step nested-PCR protocol assay. P. jirovecii was identified in the four cases. None of them had HIV infection. Two of the patients were treated empirically with trimethoprim-sulfamethoxazole, the only survivor was being one of them. Our data suggest that Pneumocystis could trigger or favor the development of AIP. Further studies are needed to evaluate the role of the pathogen in the physiopathology of this disease. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
Abdulkareem, Abdullateef; D'Souza, Ryan Steven; Patel, Nitin; Donato, Anthony A
2017-08-23
Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent cough and dyspnoea. Because of its protean features, it can mimic many more common lung conditions in the immunocompromised patient, including atypical pneumonia, Pneumocystis pneumonia and interstitial lung disease. In this article, we present the case of a 55-year-old woman who presented to our hospital with persistent dyspnoea and cough, initially suspected to have an arthritis-related interstitial lung disease. She received a final diagnosis of pulmonary toxoplasmosis after lung biopsy demonstrated Toxoplasma cysts, later confirmed by serology. Treatment with trimethoprim-sulfamethoxazole resulted in significant improvement of her respiratory symptoms after 3 months. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Choi, Yoonha; Liu, Tiffany Ting; Pankratz, Daniel G; Colby, Thomas V; Barth, Neil M; Lynch, David A; Walsh, P Sean; Raghu, Ganesh; Kennedy, Giulia C; Huang, Jing
2018-05-09
We developed a classifier using RNA sequencing data that identifies the usual interstitial pneumonia (UIP) pattern for the diagnosis of idiopathic pulmonary fibrosis. We addressed significant challenges, including limited sample size, biological and technical sample heterogeneity, and reagent and assay batch effects. We identified inter- and intra-patient heterogeneity, particularly within the non-UIP group. The models classified UIP on transbronchial biopsy samples with a receiver-operating characteristic area under the curve of ~ 0.9 in cross-validation. Using in silico mixed samples in training, we prospectively defined a decision boundary to optimize specificity at ≥85%. The penalized logistic regression model showed greater reproducibility across technical replicates and was chosen as the final model. The final model showed sensitivity of 70% and specificity of 88% in the test set. We demonstrated that the suggested methodologies appropriately addressed challenges of the sample size, disease heterogeneity and technical batch effects and developed a highly accurate and robust classifier leveraging RNA sequencing for the classification of UIP.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Ying; Field, Kevin G; Allen, Todd R.
2015-09-01
Irradiation-assisted stress corrosion cracking (IASCC) of austenitic stainless steels in Light Water Reactor (LWR) components has been linked to changes in grain boundary composition due to irradiation induced segregation (RIS). This work developed a robust RIS modeling tool to account for thermodynamics and kinetics of the atom and defect transportation under combined thermal and radiation conditions. The diffusion flux equations were based on the Perks model formulated through the linear theory of the thermodynamics of irreversible processes. Both cross and non-cross phenomenological diffusion coefficients in the flux equations were considered and correlated to tracer diffusion coefficients through Manning’s relation. Themore » preferential atomvacancy coupling was described by the mobility model, whereas the preferential atom-interstitial coupling was described by the interstitial binding model. The composition dependence of the thermodynamic factor was modeled using the CALPHAD approach. Detailed analysis on the diffusion fluxes near and at grain boundaries of irradiated austenitic stainless steels suggested the dominant diffusion mechanism for chromium and iron is via vacancy, while that for nickel can swing from the vacancy to the interstitial dominant mechanism. The diffusion flux in the vicinity of a grain boundary was found to be greatly influenced by the composition gradient formed from the transient state, leading to the oscillatory behavior of alloy compositions in this region. This work confirms that both vacancy and interstitial diffusion, and segregation itself, have important roles in determining the microchemistry of Fe, Cr, and Ni at irradiated grain boundaries in austenitic stainless steels.« less
Fibred confocal fluorescence microscopy in the diagnosis of interstitial lung diseases
Meng, Peng; Low, Su Ying; Takano, Angela; Ng, Yuen Li; Anantham, Devanand
2016-01-01
Background Accurate diagnosis is critical to both therapeutic decisions and prognostication in interstitial lung diseases (ILD). However, surgical lung biopsies carry high complication rates. Fibred confocal fluorescence microscopy (FCFM) offers an alternative as it can visualize lung tissue in vivo at the cellular level with minimal adverse events. We wanted to investigate the diagnostic utility, and safety of using FCFM for patients with ILD. Methods In patients with suspected ILD, FCFM images were obtained from multiple bronchopulmonary segments using a miniprobe inserted through the working channel of a flexible bronchoscope. The procedure was performed under moderate sedation in an outpatient setting. Morphometric measurements and fibre pattern analyses were co-related with computed tomography (CT) findings and patients’ final diagnoses based on multi-disciplinary consensus. Results One hundred and eighty four segments were imaged in 27 patients (18 males) with a median age of 67 years (range, 24–79 years). They were grouped into chronic fibrosing interstitial pneumonia (16 patients) and other ILDs. Six distinct FCFM patterns were observed: normal, increased fibres, densely packed fibres, hypercellular, thickened fibres and others/non-specific. The pattern resembling densely packed fibres was seen in at least one segment in 68.8% patients with chronic fibrosing interstitial pneumonia, but only 36.4% in other ILD (P=0.097). An association between inflammatory patterns on CT and a hypercellular pattern on FCFM was also found (P<0.001). Conclusions Our study shows the potential of FCFM in classifying ILD, but its role in further diagnosis remains limited. PMID:28149543
Predicting survival across chronic interstitial lung disease: the ILD-GAP model.
Ryerson, Christopher J; Vittinghoff, Eric; Ley, Brett; Lee, Joyce S; Mooney, Joshua J; Jones, Kirk D; Elicker, Brett M; Wolters, Paul J; Koth, Laura L; King, Talmadge E; Collard, Harold R
2014-04-01
Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis. Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation. The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia. The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.
NASA Technical Reports Server (NTRS)
Goesele, U.; Ast, D. G.
1983-01-01
Some background information on intrinsic point defects is provided and on carbon and oxygen in silicon in so far as it may be relevant for the efficiency of solar cells fabricated from EFG ribbon material. The co-precipitation of carbon and oxygen and especially of carbon and silicon self interstitials are discussed. A simple model for the electrical activity of carbon-self-interstitial agglomerates is presented. The self-interstitial content of these agglomerates is assumed to determine their electrical activity and that both compressive stresses (high self-interstitial content) and tensile stresses (low self-interstitial content) give rise to electrical activity of the agglomerates. The self-interstitial content of these carbon-related agglomerates may be reduced by an appropriate high temperature treatment and enhanced by a supersaturation of self-interstitials generated during formation of the p-n junction of solar cells. Oxygen present in supersaturation in carbon-rich silicon may be induced to form SiO, precipitates by self-interstitials generated during phosphorus diffusion. It is proposed that the SiO2-Si interface of the precipates gives rise to a continuum of donor stables and that these interface states are responsible for at least part of the light inhancement effects observed in oxygen containing EFG silicon after phosphorus diffusion.
How Radiotherapy Was Historically Used To Treat Pneumonia: Could It Be Useful Today?
Calabrese, Edward J.; Dhawan, Gaurav
2013-01-01
X-ray therapy was used to treat pneumonia during the first half of the 20th century. Fifteen studies report that approximately 700 cases of bacterial (lobar and bronchopneumonia), sulfanilamide non-responsive, interstitial, and atypical pneumonia were effectively treated by low doses of X-rays, leading to disease resolution, based on clinical symptoms, objective disease biomarkers, and mortality incidence. The capacity of the X-ray treatment to reduce mortality was similar to serum therapy and sulfonamide treatment during the same time period. Studies with four experimental animal models (i.e., mice, guinea pig, cat, and dog) with bacterial and viral pneumonia supported the clinical findings. The mechanism by which the X-ray treatment acts upon pneumonia involves the induction of an anti-inflammatory phenotype that leads to a rapid reversal of clinical symptoms, facilitating disease resolution. The capacity of low doses of X-rays to suppress inflammatory responses is a significant new concept with widespread biomedical and therapeutic applications. PMID:24348219
Pulmonary complications of cystic echinococcosis in children in Uruguay.
Sakamoto, Tsukasa; Gutierrez, Carmen
2005-08-01
Cystic echinococcal lesions surgically removed from 99 patients aged 1-15 years in Uruguay were histopathologically studied. The lesions were collected from the lungs, liver, peritoneum, omentum, pleura, ovary, appendix and perinephrium. All intact cysts were well-developed and unilocular. Pulmonary and hepatic fertile cysts in which protoscoleces were produced were in 75% and 47%, respectively, of all patients. Fertile cysts having many protoscoleces were in the lungs of a 1-year-old infant. Sixteen ruptured pulmonary cysts were found in the lungs of 13 patients and four ruptured hepatic cysts were found in the liver of three patients. Pulmonary complications were seen in patients having pulmonary echinococcal cysts. In lung tissue surrounding echinococcal cysts, pulmonary complications included chronic congestion, hemorrhage, bronchopneumonia, as well as interstitial pneumonia that included histological changes caused by bronchiolitis, organizing pneumonia and obstructive pneumonia. Liver tissue adjacent to echinococcal cysts showed atrophy of hepatic cells, proliferation of interstices, small focal hemorrhages, and infiltration of mononuclear cells. The present study shows that a close relationship exists between pulmonary echinococcosis and pneumonia. The term 'echinococcal pneumonia' is proposed for pneumonia accompanying pulmonary echinococcosis.
Izumo, Takehiro; Kondo, Mitsuko; Mae, Masahiro; Onizawa, Shigemitsu; Nagara, Naoki; Nozu, Tomoko; Tamaoki, Jun; Ohnuki, Takamasa; Nagai, Atsushi
2007-10-01
A 76-year-old man was admitted because of dry cough and dyspnea two weeks after VATS lobectomy for lung cancer. Chest radiographs and computed tomography showed interstitial shadows in the only operative lung side. Although antibiotic drugs were given because we believed it to be postoperative pneumonia, abnormal shadows on chest radiographs increased. A bronchoalveolar lavage fluid (BALF) study performed on the 21" day after operation showed that the proportions of eosinophils, basophils and mast cells had increased, and the CD4/CD8 ratio was 4.42. The drug lymphocyte stimulation test for loxoprofen sodium was positive. Based on the clinical course, laboratory data and BALF study, we arrived at a diagnosis of drug-induced pneumonia caused by loxoprofen sodium. Treatment with corticosteroid resulted in marked improvement of the chest radiographs and clinical findings. Drug-induced pneumonia usually occurs bilaterally, but it occurred only on the operative side in this case. Although rare, it is important to recognize that unilateral drug-induced pneumonia is one of the differential diagnose of postoperative pneumonia.
[Modern Views on Children's Interstitial Lung Disease].
Boĭtsova, E V; Beliashova, M A; Ovsiannikov, D Iu
2015-01-01
Interstitial lung diseases (ILD, diffuse lung diseases) are a heterogeneous group of diseases in which a pathological process primarily involved alveoli and perialveolar interstitium, resulting in impaired gas exchange, restrictive changes of lung ventilation function and diffuse interstitial changes detectable by X-ray. Children's interstitial lung diseases is an topical problem ofpediatricpulmonoogy. The article presents current information about classification, epidemiology, clinical presentation, diagnostics, treatment and prognosis of these rare diseases. The article describes the differences in the structure, pathogenesis, detection of various histological changes in children's ILD compared with adult patients with ILD. Authors cite an instance of registers pediatric patients with ILD. The clinical semiotics of ILD, the possible results of objective research, the frequency of symptoms, the features of medical history, the changes detected on chest X-rays, CT semiotics described in detail. Particular attention was paid to interstitial lung diseases, occurring mainly in newborns and children during the first two years of life, such as congenital deficiencies of surfactant proteins, neuroendocrine cell hyperplasia of infancy, pulmonary interstitial glycogenosis. The diagnostic program for children's ILD, therapy options are presented in this article.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Weiser, Philip; Qin, Ying; Yin, Weikai
Uniaxial stress experiments performed for the 3306 cm -1 vibrational line assigned to the interstitial-hydrogen, shallow-donor center in In 2O 3 reveal its symmetry and transition- moment direction. The defect alignment that can be produced by a [001] stress applied at 165 K is due to a process that is also a hydrogen- diffusion jump, providing a microscopic determination of the diffusion constant for H in In 2O 3 and its mechanism. Lastly, our experimental results strongly complement theoretical predictions for the structure and diffusion of the interstitial hydrogen donor center in In 2O 3.
Omer, Omer; Cohen, Patrizia; Neong, Shuet Fong; Smith, Geoffrey V
2016-07-01
We report the case of a 76-year-old man who presented with moderate active Crohn's colitis that was refractory to high-dose corticosteroids, mesalazine and 6-mercaptopurine. He subsequently received a trial of infliximab with poor response and was diagnosed with cytomegalovirus (CMV) colitis, improving on antiviral therapy. Three weeks into treatment he developed acute respiratory distress with hypoxaemia and diffuse pulmonary interstitial infiltrates. This was confirmed as Pneumocystis jirovecii on bronchoalveolar lavage. He responded well to treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was subsequently discharged home. Despite the favourable outcome, our case raises the question of whether chemoprophylaxis against opportunistic infections in immunosuppressed patients with inflammatory bowel disease (IBD) is appropriate. There are currently no recommendations on providing chemoprophylaxis against CMV colitis and so we focus on pneumocystis pneumonia (PCP) where wide debate surrounds the use of prophylactic TMP-SMX in HIV-negative patients. Contrasting approaches to chemoprophylaxis against PCP in IBD likely relates to a lack of clear parameters for defining risk of PCP among patient groups. This must be addressed in order to develop universal guidelines that take into account patient-dependent risk factors. Awareness of the severity of PCP among HIV-negative individuals and the current consensus on PCP prophylaxis in IBD must be raised in order to minimise the risk of PCP and drive research in this controversial area.
Omer, Omer; Cohen, Patrizia; Neong, Shuet Fong; Smith, Geoffrey V
2016-01-01
We report the case of a 76-year-old man who presented with moderate active Crohn's colitis that was refractory to high-dose corticosteroids, mesalazine and 6-mercaptopurine. He subsequently received a trial of infliximab with poor response and was diagnosed with cytomegalovirus (CMV) colitis, improving on antiviral therapy. Three weeks into treatment he developed acute respiratory distress with hypoxaemia and diffuse pulmonary interstitial infiltrates. This was confirmed as Pneumocystis jirovecii on bronchoalveolar lavage. He responded well to treatment with trimethoprim-sulfamethoxazole (TMP-SMX) and was subsequently discharged home. Despite the favourable outcome, our case raises the question of whether chemoprophylaxis against opportunistic infections in immunosuppressed patients with inflammatory bowel disease (IBD) is appropriate. There are currently no recommendations on providing chemoprophylaxis against CMV colitis and so we focus on pneumocystis pneumonia (PCP) where wide debate surrounds the use of prophylactic TMP-SMX in HIV-negative patients. Contrasting approaches to chemoprophylaxis against PCP in IBD likely relates to a lack of clear parameters for defining risk of PCP among patient groups. This must be addressed in order to develop universal guidelines that take into account patient-dependent risk factors. Awareness of the severity of PCP among HIV-negative individuals and the current consensus on PCP prophylaxis in IBD must be raised in order to minimise the risk of PCP and drive research in this controversial area. PMID:28839859
Holter, Karl Erik; Kehlet, Benjamin; Devor, Anna; Sejnowski, Terrence J; Dale, Anders M; Omholt, Stig W; Ottersen, Ole Petter; Nagelhus, Erlend Arnulf; Mardal, Kent-André; Pettersen, Klas H
2017-09-12
The brain lacks lymph vessels and must rely on other mechanisms for clearance of waste products, including amyloid [Formula: see text] that may form pathological aggregates if not effectively cleared. It has been proposed that flow of interstitial fluid through the brain's interstitial space provides a mechanism for waste clearance. Here we compute the permeability and simulate pressure-mediated bulk flow through 3D electron microscope (EM) reconstructions of interstitial space. The space was divided into sheets (i.e., space between two parallel membranes) and tunnels (where three or more membranes meet). Simulation results indicate that even for larger extracellular volume fractions than what is reported for sleep and for geometries with a high tunnel volume fraction, the permeability was too low to allow for any substantial bulk flow at physiological hydrostatic pressure gradients. For two different geometries with the same extracellular volume fraction the geometry with the most tunnel volume had [Formula: see text] higher permeability, but the bulk flow was still insignificant. These simulation results suggest that even large molecule solutes would be more easily cleared from the brain interstitium by diffusion than by bulk flow. Thus, diffusion within the interstitial space combined with advection along vessels is likely to substitute for the lymphatic drainage system in other organs.
Acute fibrinous and organizing pneumonia: A report of 13 cases in a tertiary university hospital.
Gomes, Rita; Padrão, Eva; Dabó, Hans; Soares Pires, Filipa; Mota, Patrícia; Melo, Natália; Jesus, José Miguel; Cunha, Rui; Guimarães, Susana; Souto Moura, Conceição; Morais, António
2016-07-01
Acute fibrinous and organizing pneumonia (AFOP) is a rare diffuse pulmonary disease, but it is not yet known whether it is a distinct form of interstitial pneumonia or simply a reflection of a tissue sampling issue. Cross-sectional evaluation of clinical and radiological findings, treatments, and outcomes for patients with histologically confirmed AFOP at a tertiary university hospital between 2002 and 2015. Thirteen patients (7 women, 53.8%) with a mean ± SD age of 53.5 ± 16.1 years were included. The main symptoms were fever (69.2%), cough (46.2%), and chest pain (30.8%). All patients presented a radiological pattern of consolidation and 5 (38.5%) had simultaneous ground-glass areas. Histology was obtained by computed tomography-guided transthoracic biopsy in 61.5% of cases and by surgical lung biopsy in the remaining cases. Several potential etiologic factors were identified. Eight patients (61.5%) had hematologic disorders and 3 had undergone an autologous hematopoietic cell transplant. Two (15.4%) had microbiologic isolates, 5 (38.4%) had drug-induced lung toxicity, and 2 (15.4%) were classified as having idiopathic AFOP. In addition to antibiotics and diuretics used to treat the underlying disease, the main treatment was corticosteroids, combined in some cases with immunosuppressants. Median survival was 78 months and 6 patients (46.2%) were still alive at the time of analysis. Our findings for this series of patients confirm that AFOP is a nonspecific reaction to various agents with a heterogeneous clinical presentation and clinical course that seems to be influenced mainly by the severity of the underlying disorder.
NASA Astrophysics Data System (ADS)
Sangiovanni, Davide G.; Alling, Björn; Hultman, Lars; Abrikosov, Igor A.
2015-03-01
We use ab-initio and classical molecular dynamics (AIMD, CMD) to simulate diffusion of N vacancy and N self-interstitial point-defects in B1 TiN. The physical properties of TiN, important material system for thin film and coatings applications, are largely dictated by concentration and mobility of point defects. We determine N dilute-point-defect diffusion pathways, activation energies, attempt frequencies, and diffusion coefficients as a function of temperature. In addition, MD simulations reveal an unanticipated atomistic process, which controls the spontaneous formation of N-self-interstitial/N-vacancy pairs (Frenkel pairs) in defect-free TiN. This entails that a N lattice atom leaves its bulk position and bonds to a neighboring N lattice atom. In most cases, Frenkel-pair NI and NV recombine within a fraction of ns; 50% of these processes result in the exchange of two nitrogen lattice atoms. Occasionally, however, Frenkel-pair N-interstitial atoms permanently escape from the anion vacancy site, thus producing unpaired NI and NV point defects. The Knut and Alice Wallenberg foundation (Isotope Project, 2011.0094), the Swedish Research Council (VR) Linköping Linnaeus Initiative LiLi-NFM (Grant 2008-6572), and the Swedish Government Strategic Research (Grant MatLiU 2009-00971).
NASA Astrophysics Data System (ADS)
Sangiovanni, D. G.; Alling, B.; Steneteg, P.; Hultman, L.; Abrikosov, I. A.
2015-02-01
We use ab initio and classical molecular dynamics (AIMD and CMD) based on the modified embedded-atom method (MEAM) potential to simulate diffusion of N vacancy and N self-interstitial point defects in B 1 TiN. TiN MEAM parameters are optimized to obtain CMD nitrogen point-defect jump rates in agreement with AIMD predictions, as well as an excellent description of Ti Nx(˜0.7
High-power diffusing-tip fibers for interstitial photocoagulation
NASA Astrophysics Data System (ADS)
Sinofsky, Edward L.; Farr, Norman; Baxter, Lincoln; Weiler, William
1997-05-01
A line of optical fiber based diffusing tips has been designed, developed, and tested that are capable of distributing tens of watts of cw laser power over lengths ranging from two millimeters to over 10 cm. The result is a flexible non-stick diffuser capable of coagulating large volumes of tissue in reasonably short exposures of 3 - 5 minutes. Sub-millimeter diameter devices have a distinct effect on reducing the force needed to insert the applicator interstitially into tissue. Utilizing our design approach, we have produced diffusers based on 200 micrometer core fiber that has delivered over 35 watts of Nd:YAG energy over diffusion lengths as short as 4 mm. These applicators are being tested for applications in oncology, cardiology, electrophysiology, urology and gynecology.
NASA Astrophysics Data System (ADS)
Fang, Tilden T.; Fang, Wingra T. C.; Griffin, Peter B.; Plummer, James D.
1996-02-01
Investigation of boron diffusion in strained silicon germanium buried layers reveals a fractional interstitial component of boron diffusion (fBI) in Se0.8Ge0.2 approximately equal to the fBI value in silicon. In conjunction with computer-simulated boron profiles, the results yield an absolute lower-bound of fBI in Si0.8Ge0.2 of ˜0.8. In addition, the experimental methodology provides a unique vehicle for measuring the segregation coefficient; oxidation-enhanced diffusion is used instead of an extended, inert anneal to rapidly diffuse the dopant to equilibrium levels across the interface, allowing the segregation coefficient to be measured more quickly.
Xaubet, Antoni; Ancochea, Julio; Bollo, Elena; Fernández-Fabrellas, Estrella; Franquet, Tomás; Molina-Molina, Maria; Montero, Maria Angeles; Serrano-Mollar, Anna
2013-08-01
Idiopathic pulmonary fibrosis is defined as a chronic fibrosing interstitial pneumonia limited to the lung, of unknown cause, with poor prognosis and few treatment options. In recent years there has been an increase in their prevalence, probably due to the optimization of diagnostic methods and increased life expectancy. The ATS/ERS Consensus (2000) established the diagnostic criteria and recommendations for the assessment of the disease course and treatment. Later studies have helped to redefine diagnostic criteria and treatment options. In 2011, an international consensus was published, establishing diagnostic criteria and new treatment strategies. These guidelines have been updated with the newest aspects of diagnosis and treatment of idiopathic pulmonary fibrosis. A level of evidence has been identified for the most relevant questions, particularly with regard to treatment options. Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.
Chronic eosinophilic pneumonia presenting with ipsilateral pleural effusion: a case report.
Sriratanaviriyakul, Narin; La, Hanh H; Albertson, Timothy E
2016-08-12
Chronic eosinophilic pneumonia is a rare idiopathic interstitial lung disease. The nearly pathognomonic radiographic finding is the peripheral distribution of alveolar opacities. Pleural effusions are rarely seen. We report a case of chronic eosinophilic pneumonia with transudative eosinophilic pleural effusion. A 57-year-old Hispanic woman, a nonsmoker with a history of controlled asthma, presented to the hospital with unresolving pneumonia despite three rounds of antibiotics over a 2-month period. She was later diagnosed with chronic eosinophilic pneumonia based on the presence of peripheral blood eosinophilia, the peripheral distribution of alveolar infiltrates on chest radiograph, and a lung parenchymal biopsy with infiltrates of eosinophils. Upon presentation, our patient had a right-sided moderate-sized pleural effusion. The pleural fluid profile was consistent with a transudative effusion with eosinophil predominance. Our patient responded promptly to oral corticosteroid treatment in a few days. The pulmonary infiltrates and pleural effusion subsided on a 1-month follow-up chest radiograph after starting corticosteroid treatment. We report the first case of chronic eosinophilic pneumonia presenting with pneumonia with ipsilateral transudative eosinophilic pleural effusion. Like other cases of chronic eosinophilic pneumonia, early recognition and diagnosis is essential and prompt treatment with corticosteroids is the mainstay of therapy. Pleural effusion resolved without the further need for therapeutic thoracentesis.
Histopathology of ventilator-associated pneumonia (VAP) and its clinical implications.
Torres, A; Fábregas, N; Arce, Y; López-Boado, M A
1999-01-01
Ventilator-associated pneumonia (VAP) is a diffuse polymicrobial and dynamic process, with heterogeneous distribution of lesions, showing different degrees of histological evolution predominating in the dependent lung zones, in which microbiology and histology can be dissociated. This might explain why blind endobronchial techniques to collect respiratory secretions have similar accuracy compared to visually guided samples, explaining the difficulties in validating any methods for its diagnosis. In the clinical setting the association of acute lung injury (ALI) and pneumonia is controversial. However, it is rare to detect diffuse alveolar damage (DAD) in absence of histological signs of pneumonia, probably evidencing that ALI favors the development of pneumonia. Histopathologically, it is difficult to distinguish initial and resolution phases of DAD from pneumonia and vice versa. On the other hand, there is a clear relationship between antimicrobial treatment and the decreased lung bacterial burden which strengthens the importance of distal airway sampling before starting antibiotic therapy.
Ramírez-Romero, Rafael; Nevárez-Garza, Alicia M.; Rodríguez-Tovar, Luis E.; Wong-González, Alfredo; Ledezma-Torres, Rogelio A.; Hernández-Vidal, Gustavo
2012-01-01
Most of the natural cases of pneumonia in feedlot cattle are characterized by a longer clinical course due to chronic lung lesions. Microscopically, these lesions include interstitial fibroplasia, bronchitis, bronchiectasis, bronchiolitis obliterans, and epithelial metaplasia of the airways. Herein, the aim was to review, under a medical perspective, the pathologic mechanisms operating in these chronic pneumonic lesions in calves. Based on the similarities of these changes to those reported in bronchiolitis obliterans/organising pneumonia (BO/OP) and chronic obstructive pulmonary disease (COPD) in human beings, calves are proposed as an alternative animal model. PMID:22629176
Phosphorus-defect interactions during thermal annealing of ion implanted silicon
NASA Astrophysics Data System (ADS)
Keys, Patrick Henry
Ion implantation of dopant atoms into silicon generates nonequilibrium levels of crystal defects that can lead to the detrimental effects of transient enhanced diffusion (TED), incomplete dopant activation, and p-n junction leakage. In order to control these effects, it is vital to have a clear understanding of dopant-defect interactions and develop models that account for these interactions. This research focuses on experimentally investigating and modeling the clustering of phosphorus dopant atoms with silicon interstitials. Damage recovery of 40keV Si+ implants in phosphorus doped wells is experimentally analyzed. The effects of background phosphorus concentration, self implant dose, and anneal temperature are investigated. Phosphorus concentrations ranging from 2.0 x 1017 to 4.0 x 1019 cm-3 and Si+ doses ranging from 5.0 x 1013 cm-2 to 2.0 x 1014 cm-2 are studied during 650-800°C anneals. A dramatic reduction in the number of interstitials bound in {311} defects with increasing phosphorus background concentration is observed. It is suggested that the reduction of interstitials in {311} defects at high phosphorus concentrations is due to the formation of phosphorus-interstitial clusters (PICs). The critical concentration for clustering (approximately 1.0 x 1019 cm-3 at 750°C) is strongly temperature dependent and in close agreement with the kink concentration of phosphorus diffusion. Information gained from these "well experiments" is applied to the study of direct phosphorus implantation. An experimental study is conducted on 40keV phosphorus implanted to a dose of 1.0 x 1014 cm-2 during 650-800°C anneals. Electrically inactive PICs are shown to form at concentrations below the solid solubility limit due to high interstitial supersaturations. Data useful for developing a model to accurately predict phosphorus diffusion under nonequilibrium conditions are extracted from the experimental results. A cluster-mediated diffusion model is developed using the Florida Object Oriented Process Simulator (FLOOPS). The nucleation of defects is controlled by the diffusion-limited competition for excess interstitials between PICs and {311} clusters. The release of interstitials is driven by cluster dissolution. Modeling results show a strong correlation to those experimentally observed over a wide temporal and thermal domain using a single set of parameters. Improvements in process simulator accuracy are demonstrated with respect to dopant activation, TED, and dose loss.
Tomassetti, Sara; Wells, Athol U; Costabel, Ulrich; Cavazza, Alberto; Colby, Thomas V; Rossi, Giulio; Sverzellati, Nicola; Carloni, Angelo; Carretta, Elisa; Buccioli, Matteo; Tantalocco, Paola; Ravaglia, Claudia; Gurioli, Christian; Dubini, Alessandra; Piciucchi, Sara; Ryu, Jay H; Poletti, Venerino
2016-04-01
Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.
Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review
Iqbal, Kundan; Kelly, Clive
2015-01-01
Rheumatoid arthritis (RA) is a systemic autoimmune disease affecting 0.5–1% of the worldwide population. Whilst predominantly causing chronic pain and inflammation in synovial joints, it is also associated with significant extra-articular manifestations in a large proportion of patients. Among the various pulmonary manifestations, interstitial lung disease (ILD), a progressive fibrotic disease of the lung parenchyma, is the commonest and most important, contributing significantly to increased morbidity and mortality. The most frequent patterns of RA-associated ILD (RA-ILD) are usual interstitial pneumonia and nonspecific interstitial pneumonia. New insights during the past several years have highlighted the epidemiological impact of RA-ILD and have begun to identify factors contributing to its pathogenesis. Risk factors include smoking, male sex, human leukocyte antigen haplotype, rheumatoid factor and anticyclic citrullinated protein antibodies (ACPAs). Combined with clinical information, chest examination and pulmonary function testing, high-resolution computed tomography of the chest forms the basis of investigation and allows assessment of subtype and disease extent. The management of RA-ILD is a challenge. Several therapeutic agents have been suggested in the literature but as yet no large randomized controlled trials have been undertaken to guide clinical management. Therapy is further complicated by commonly prescribed drugs of proven articular benefit such as methotrexate, leflunomide (LEF) and anti-tumour necrosis factor α agents having been implicated in both ex novo occurrence and acceleration of existing ILD. Agents that offer promise include immunomodulators such as mycophenolate and rituximab as well as newly studied antifibrotic agents. In this review, we discuss the current literature to evaluate recommendations for the management of RA-ILD and discuss key gaps in our knowledge of this important disease. PMID:26622326
Interstitial pneumonia with autoimmune features: an additional risk factor for ARDS?
Grasselli, Giacomo; Vergnano, Beatrice; Pozzi, Maria Rosa; Sala, Vittoria; D'Andrea, Gabriele; Scaravilli, Vittorio; Mantero, Marco; Pesci, Alberto; Pesenti, Antonio
2017-09-18
Interstitial pneumonia with autoimmune features (IPAF) identifies a recently recognized autoimmune syndrome characterized by interstitial lung disease and autoantibodies positivity, but absence of a specific connective tissue disease diagnosis or alternative etiology. We retrospectively reviewed the clinical presentation, diagnostic workup and management of seven critically ill patients who met diagnostic criteria for IPAF. We compared baseline characteristics and clinical outcome of IPAF patients with those of the population of ARDS patients admitted in the same period. Seven consecutive patients with IPAF admitted to intensive care unit for acute respiratory distress syndrome (ARDS) were compared with 78 patients with ARDS secondary to a known risk factor and with eight ARDS patients without recognized risk factors. Five IPAF patients (71%) survived and were discharged alive from ICU: Their survival rate was equal to that of patients with a known risk factor (71%), while the subgroup of patients without risk factors had a markedly lower survival (38%). According to the Berlin definition criteria, ARDS was severe in four IPAF patients and moderate in the remaining three. All had multiple organ dysfunction at presentation. The most frequent autoantibody detected was anti-SSA/Ro52. All patients required prolonged mechanical ventilation (median duration 49 days, range 10-88); four received extracorporeal membrane oxygenation and one received low-flow extracorporeal CO 2 removal. All patients received immunosuppressive therapy. This is the first description of a cohort of critical patients meeting the diagnostic criteria for IPAF presenting with ARDS. This diagnosis should be considered in any critically ill patient with interstitial lung disease of unknown origin. While management is challenging and level of support high, survival appears to be good and comparable to that of patients with ARDS associated with a known clinical insult.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Isoda, Taiga; Uematsu, Masashi; Itoh, Kohei M., E-mail: kitoh@appi.keio.ac.jp
2015-09-21
Si self-diffusion in the presence of end-of-range (EOR) defects is investigated using {sup nat}Si/{sup 28}Si isotope multilayers. The isotope multilayers were amorphized by Ge ion implantation, and then annealed at 800–950 °C. The behavior of Si self-interstitials is investigated through the {sup 30}Si self-diffusion. The experimental {sup 30}Si profiles show further enhancement of Si self-diffusion at the EOR defect region, in addition to the transient enhanced diffusion via excess Si self-interstitials by EOR defects. To explain this additional enhanced diffusion, we propose a model which takes into account enhanced diffusion by tensile strain originated from EOR defects. The calculation results basedmore » on this model have well reproduced the experimental {sup 30}Si profiles.« less
USDA-ARS?s Scientific Manuscript database
Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infectio...
Naito, Tomoyuki; Tanaka, Yosuke; Hino, Mitsunori; Gemma, Akihiko
2017-01-01
A 72-year-old woman was admitted to our hospital and was diagnosed with interstitial pneumonia (IP) associated with amyopathic dermatomyositis (ADM). The patient experienced three acute IP exacerbations in the 7 years that followed, which were each treated and resolved with steroid pulse therapy. The patient was closely examined for respiratory failure with right heart catheterization (RHC), which demonstrated that she had a mean pulmonary artery pressure (mPAP) of 34 mmHg. The patient was thus diagnosed as having pulmonary hypertension (PH) associated with anti-synthetase syndrome (ASS) and was started on bosentan therapy, which led to improvements in mPAP as well as in subjective symptoms over time. Indeed, she had had no acute exacerbations with serum markers of IP remaining low over 6 years following initiation of bosentan therapy, suggesting that bosentan may have a role in controlling IP. In addition, she was confirmed to be anti-ARS antibody-positive after 5 years of bosentan therapy, when anti-aminoacyl tRNA synthetase (anti-ARS) antibody testing became available.
Acute interstitial pneumonia in feedlot cattle: effects of feeding feather meal or vitamin E
Stanford, Kim; McAllister, Tim A.; Ayroud, Mejid; Bray, Tammy M.; Yost, Garold S.
2007-01-01
We evaluated the effects of feeding 1.5% cysteine-rich feather meal or 550 IU of vitamin E for 40 d before slaughter on the rates of death and emergency slaughter due to acute interstitial pneumonia (AIP) in commercial feedlots. Blood and lung tissue were collected at slaughter from 83 animals clinically diagnosed with AIP, 40 asymptomatic penmates, and 40 heifers receiving either feather meal (20) or vitamin E (20); the left lung was subsampled for histologic examination. Blood and lung tissue were analyzed for thiol adducts of 3-methyleneindolenine (3ME) and reduced glutathione. Supplementation with feather meal or vitamin E had no effect on the rates of death and emergency slaughter attributable to AIP and did not influence the levels of 3ME or reduced glutathione in blood or lung tissue. Although supplementation with greater amounts of feather meal or vitamin E may have been necessary to significantly affect factors related to feedlot AIP, increased supplementation would be uneconomical for commercial feedlots, given the relatively low incidence of AIP. PMID:17479779
Exogenous lipoid pneumonia – a case report of a fire-eater
Pielaszkiewicz-Wydra, Magdalena; Homola-Piekarska, Bożena; Szcześniak, Ewa; Ciołek-Zdun, Monika; Fall, Andrzej
2012-01-01
Summary Background: Exogenous lipoid pneumonia is an uncommon condition caused by inhalation or aspiration of a fatty substance. It usually presents as chronic respiratory illness mimicking interstitial lung diseases. Acute exogenous lipoid pneumonia is uncommon and typically is caused by an episode of aspiration of a large quantity of a petroleum-based product. Radiological findings vary and may imitate many other diseases. Case Report: We present a rare case of acute exogenous lipoid pneumonia in a fire-eater who aspirated liquid paraffin during his flame-blowing show (fire-eater’s lung). He was admitted to the hospital with productive cough, fever, hemoptysis, chest pain and dyspnea. Diagnosis was made on the basis of history of exposure to fatty substance, characteristic findings in CT examination and presence of lipid-laden macrophages in bronchoalveolar lavage fluid. Conclusions: Acute exogenous lipoid pneumonia is a very rare disease that typically occurs in fire-eaters and is called a fire-eater’s lung. The diagnosis is made on the basis of typical history and radiological, as well as histopathological findings. PMID:23269939
Siegel, C; Johnston, S; Adair, S
1990-10-01
The isolation of measles virus in primary Rhesus monkey kidney cells (PRMK) in patients with documented giant-cell pneumonia who have presented without a rash is limited. The diagnosis usually is made by cytologic examination of nasal or bronchial secretions in which characteristic multinucleated giant cells with intranuclear and intracytoplasmic inclusion bodies are observed. The diagnosis of giant-cell pneumonia has been associated with measles virus but not exclusively. Canine distemper, herpes group viruses, and parainfluenza infections have been associated with these cells. In addition, vitamin A deficiency also has been cytologically associated with multinucleated giant cells. The authors describe the isolation of measles virus from bronchial washing and sputum in PRMK cells at 4 days from an 11-year-old child with acute interstitial pneumonia who was in remission for acute lymphocytic leukemia. Classic cytopathologic effect (CPE) consisting of syncytial and hole formation on the PRMK monolayer was apparent. In addition, a foamy appearance of the monolayer was noted in an otherwise clean lot of monkey cells. Confirmatory testing with measles antibody of the infected areas of the monolayer by indirect immunofluorescence (IFA) was positive for measles antigen and negative for mumps, parainfluenza (types I, II, and III) and influenza A and B virus. Serologic studies for measles antibody revealed an IFA IgG titer of greater than 1:10,240, and an IgM titer of 1:128. Cytologic examination of the same bronchial fluid revealed the typical giant cells with characteristic inclusions associated with measles virus. Because this disease usually is severe, and often fatal, prompt recognition of this virus is essential, not only to the patient, who can be treated with immunoglobulin and/or antiviral therapy, but also to prevent the spread of the virus to other patients and medical personnel. These findings also support direct evidence for the etiologic role of measles virus in giant-cell pneumonia that has been detected either histologically or cytologically and in tissue culture at autopsy.
NASA Astrophysics Data System (ADS)
Tikhonchev, M.; Svetukhin, V.; Kapustin, P.
2017-09-01
Ab initio calculations predict high positive binding energy (˜1 eV) between niobium atoms and self-interstitial configurations in hcp zirconium. It allows the expectation of increased niobium fraction in self-interstitials formed under neutron irradiation in atomic displacement cascades. In this paper, we report the results of molecular dynamics simulation of atomic displacement cascades in Zr-0.5%Nb binary alloy and pure Zr at the temperature of 300 K. Two sets of n-body interatomic potentials have been used for the Zr-Nb system. We consider a cascade energy range of 2-20 keV. Calculations show close estimations of the average number of produced Frenkel pairs in the alloy and pure Zr. A high fraction of Nb is observed in the self-interstitial configurations. Nb is mainly detected in single self-interstitial configurations, where its fraction reaches tens of percent, i.e. more than its tenfold concentration in the matrix. The basic mechanism of this phenomenon is the trapping of mobile self-interstitial configurations by niobium. The diffusion of pure zirconium and mixed zirconium-niobium self-interstitial configurations in the zirconium matrix at 300 K has been simulated. We observe a strong dependence of the estimated diffusion coefficients and fractions of Nb in self-interstitials produced in displacement cascades on the potential.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Varley, J. B.; Lordi, V.; He, X.
2016-01-14
We investigate point defects in CdS buffer layers that may arise from intermixing with Cu(In,Ga)Se{sub 2} (CIGSe) or Cu{sub 2}ZnSn(S,Se){sub 4} (CZTSSe) absorber layers in thin-film photovoltaics (PV). Using hybrid functional calculations, we characterize the migration barriers of Cu, In, Ga, Se, Sn, Zn, Na, and K impurities and assess the activation energies necessary for their diffusion into the bulk of the buffer. We find that Cu, In, and Ga are the most mobile defects in CIGS-derived impurities, with diffusion expected to proceed into the buffer via interstitial-hopping and cadmium vacancy-assisted mechanisms at temperatures ∼400 °C. Cu is predicted to stronglymore » favor migration paths within the basal plane of the wurtzite CdS lattice, which may facilitate defect clustering and ultimately the formation of Cu-rich interfacial phases as observed by energy dispersive x-ray spectroscopic elemental maps in real PV devices. Se, Zn, and Sn defects are found to exhibit much larger activation energies and are not expected to diffuse within the CdS bulk at temperatures compatible with typical PV processing temperatures. Lastly, we find that Na interstitials are expected to exhibit slightly lower activation energies than K interstitials despite having a larger migration barrier. Still, we find both alkali species are expected to diffuse via an interstitially mediated mechanism at slightly higher temperatures than enable In, Ga, and Cu diffusion in the bulk. Our results indicate that processing temperatures in excess of ∼400 °C will lead to more interfacial intermixing with CdS buffer layers in CIGSe devices, and less so for CZTSSe absorbers where only Cu is expected to significantly diffuse into the buffer.« less
Ponces Bento, D; Esteves, F; Matos, O; Miranda, A C; Ventura, F; Araújo, C; Mansinho, K
2013-01-01
It is well established that HIV patients are at high risk of opportunistic infections (OI), like the ones caused by Pneumocystis jirovecii, a worldwide pathogen implicated in interstitial pneumonia (PcP). We present a case of a newly diagnosed HIV-1 patient with multiple OI, including a persistent form of PcP, an invasive aspergillosis (IA), cytomegalovirus and Mycobacterium xenopi lung infection. We describe the combination of laboratorial screening, surgery and antimicrobial therapy that were crucial for patient recovery. Copyright © 2012 Sociedade Portuguesa de Pneumologia. Published by Elsevier España. All rights reserved.
Cs diffusion in SiC high-energy grain boundaries
NASA Astrophysics Data System (ADS)
Ko, Hyunseok; Szlufarska, Izabela; Morgan, Dane
2017-09-01
Cesium (Cs) is a radioactive fission product whose release is of concern for Tristructural-Isotropic fuel particles. In this work, Cs diffusion through high energy grain boundaries (HEGBs) of cubic-SiC is studied using an ab-initio based kinetic Monte Carlo (kMC) model. The HEGB environment was modeled as an amorphous SiC, and Cs defect energies were calculated using the density functional theory (DFT). From defect energies, it was suggested that the fastest diffusion mechanism is the diffusion of Cs interstitial in an amorphous SiC. The diffusion of Cs interstitial was simulated using a kMC model, based on the site and transition state energies sampled from the DFT. The Cs HEGB diffusion exhibited an Arrhenius type diffusion in the range of 1200-1600 °C. The comparison between HEGB results and the other studies suggests not only that the GB diffusion dominates the bulk diffusion but also that the HEGB is one of the fastest grain boundary paths for the Cs diffusion. The diffusion coefficients in HEGB are clearly a few orders of magnitude lower than the reported diffusion coefficients from in- and out-of-pile samples, suggesting that other contributions are responsible, such as radiation enhanced diffusion.
Low Temperature Diffusion Transformations in Fe-Ni-Ti Alloys During Deformation and Irradiation
NASA Astrophysics Data System (ADS)
Sagaradze, Victor; Shabashov, Valery; Kataeva, Natalya; Kozlov, Kirill; Arbuzov, Vadim; Danilov, Sergey; Ustyugov, Yury
2018-03-01
The deformation-induced dissolution of Ni3Ti intermetallics in the matrix of austenitic alloys of Fe-36Ni-3Ti type was revealed in the course of their cascade-forming neutron irradiation and cold deformation at low temperatures via employment of Mössbauer method. The anomalous deformation-related dissolution of the intermetallics has been explained by the migration of deformation-induced interstitial atoms from the particles into a matrix in the stress field of moving dislocations. When rising the deformation temperature, this process is substituted for by the intermetallics precipitation accelerated by point defects. A calculation of diffusion processes has shown the possibility of the realization of the low-temperature diffusion of interstitial atoms in configurations of the crowdions and dumbbell pairs at 77-173 K. The existence of interstitial atoms in the Fe-36Ni alloy irradiated by electrons or deformed at 77 K was substantiated in the experiments of the electrical resistivity measurements.
Transient enhanced diffusion in preamorphized silicon: the role of the surface
NASA Astrophysics Data System (ADS)
Cowern, N. E. B.; Alquier, D.; Omri, M.; Claverie, A.; Nejim, A.
1999-01-01
Experiments on the depth dependence of transient enhanced diffusion (TED) of boron during rapid thermal annealing of Ge-preamorphized layers reveal a linear decrease in the diffusion enhancement between the end-of-range (EOR) defect band and the surface. This behavior, which indicates a quasi-steady-state distribution of excess interstitials, emitted from the EOR band and absorbed at the surface, is observed for annealing times as short as 1 s at 900°C. Using an etching procedure we vary the distance xEOR from the EOR band to the surface in the range 80-175 nm, and observe how this influences the interstitial supersaturation, s( x). The supersaturations at the EOR band and the surface remain unchanged, while the gradient d s/d x, and thus the flux to the surface, varies inversely with xEOR. This confirms the validity of earlier modelling of EOR defect evolution in terms of Ostwald ripening, and provides conclusive evidence that the surface is the dominant sink for interstitials during TED.
NASA Astrophysics Data System (ADS)
Le, Kelvin; Johsi, Chet; Figueroa, Daniel; Goddard, Jessica; Li, Xiaosong; Towner, Rheal A.; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.
2011-03-01
Laser immunotherapy (LIT), using non-invasive laser irradiation, has resulted in promising outcomes in the treatment of late-stage cancer patients. However, the tissue absorption of laser light limits the clinical applications of LIT in patients with dark skin, or with deep tumors. The present study is designed to investigate the thermal effects of interstitial irradiation using an 805-nm laser with a cylindrical diffuser, in order to overcome the limitations of the non-invasive mode of treatment. Cow liver and rat tumors were irradiated using interstitial fiber. The temperature increase was monitored by thermocouples that were inserted into the tissue at different sites around the cylinder fiber. Three-dimensional temperature distribution in target tissues during and after interstitial laser irradiation was also determined by Proton Resonance Frequency. The preliminary results showed that the output power of laser and the optical parameters of the target tissue determined the light distribution in the tissue. The temperature distributions varied in the tissue according to the locations relative to the active tip of the cylindrical diffuser. The temperature increase is strongly related to the laser power and irradiation time. Our results using thermocouples and optical sensors indicated that the PRF method is reliable and accurate for temperature determination. Although the inhomogeneous biological tissues could result in temperature fluctuation, the temperature trend still can be reliable enough for the guidance of interstitial irradiation. While this study provides temperature profiles in tumor tissue during interstitial irradiation, the biological effects of the irradiation remain unclear. Future studies will be needed, particularly in combination with the application of immunostimulant for inducing tumor-specific immune responses in the treatment of metastatic tumors.
First-principles investigation of diffusion and defect properties of Fe and Ni in Cr2O3
NASA Astrophysics Data System (ADS)
Rak, Zs.; Brenner, D. W.
2018-04-01
Diffusion of Fe and Ni and the energetics of Fe- and Ni-related defects in chromium oxide (α-Cr2O3) are investigated using first-principles Density Functional Theory calculations in combination with the climbing-image nudged elastic band method. The orientations of the spin magnetic moments of the migrating ions are taken into account and their effects on migration barriers are examined. Several possible diffusion pathways were explored through interstitial and vacancy mechanisms, and it was found that the principal mode of ion transport in Cr2O3 is via vacancies. Both interstitial- and vacancy-mediated diffusions are anisotropic, with diffusion being faster in the z-direction. The energetics of defect formation indicates that the Ni-related defects are less stable than the Fe-related ones. This is consistent with Ni-diffusion being faster than Fe-diffusion. The results are compared with previous theoretical and experimental data and possible implications in corrosion control are discussed.
Quantitative dual-probe microdialysis: mathematical model and analysis.
Chen, Kevin C; Höistad, Malin; Kehr, Jan; Fuxe, Kjell; Nicholson, Charles
2002-04-01
Steady-state microdialysis is a widely used technique to monitor the concentration changes and distributions of substances in tissues. To obtain more information about brain tissue properties from microdialysis, a dual-probe approach was applied to infuse and sample the radiotracer, [3H]mannitol, simultaneously both in agar gel and in the rat striatum. Because the molecules released by one probe and collected by the other must diffuse through the interstitial space, the concentration profile exhibits dynamic behavior that permits the assessment of the diffusion characteristics in the brain extracellular space and the clearance characteristics. In this paper a mathematical model for dual-probe microdialysis was developed to study brain interstitial diffusion and clearance processes. Theoretical expressions for the spatial distribution of the infused tracer in the brain extracellular space and the temporal concentration at the probe outlet were derived. A fitting program was developed using the simplex algorithm, which finds local minima of the standard deviations between experiments and theory by adjusting the relevant parameters. The theoretical curves accurately fitted the experimental data and generated realistic diffusion parameters, implying that the mathematical model is capable of predicting the interstitial diffusion behavior of [3H]mannitol and that it will be a valuable quantitative tool in dual-probe microdialysis.
Acute fibrinous and organising pneumonia.
Guimarães, Catarina; Sanches, Inês; Ferreira, Catarina
2012-03-20
Acute fibrinous and organising pneumonia (AFOP) was recently described as an unusual pattern of diffuse lung disease. Particular characteristics make the differential diagnosis with the well recognised clinical patterns of diffuse alveolar damage, cryptogenic organising pneumonia or eosinophilic pneumonia. The lack of hyaline membranes, the presence of intra-alveolar fibrin, absence of noticeable eosinophils and patchy distribution suggests that AFOP define a distinct histological pattern. The authors describe the case of a woman diagnosed with AFOP after surgical lung biopsy, in association with primary biliary cirrhosis. The patient presented dyspnoea, fatigue, dry cough and thoracic pain. The CT scan showed bilateral patchy infiltrates predominantly in the lower lobes. Flexible bronchoscopy and subsidiary techniques were inconclusive and biopsy through video-assisted thoracoscopic surgery led to anatomopathological diagnosis of AFOP. The patient is having a good clinical response to prednisone.
Oxidative Corrosion of the UO 2 (001) Surface by Nonclassical Diffusion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stubbs, Joanne E.; Biwer, Craig A.; Chaka, Anne M.
Uranium oxide is central to every stage of the nuclear fuel cycle, from mining through fuel fabrication and use, to waste disposal and environmental cleanup. Its chemical and mechanical stability are intricately linked to the concentration of interstitial O atoms within the structure and the oxidation state of U. We have previously shown that during corrosion of the UO2 (111) surface under either 1 atm O2 gas or oxygenated water at room temperature, oxygen interstitials diffuse into the substrate to form a superlattice with three-layer periodicity. In the current study, we present results from surface x-ray scattering that reveal themore » structure of the oxygen diffusion profile beneath the (001) surface. The first few layers below the surface oscillate strongly in their surface-normal lattice parameters, suggesting preferential interstitial occupation of every other layer below the surface, which is geometrically consistent with the interstitial network that forms below the oxidized (111) surface. Deeper layers are heavily contracted and indicate that the oxidation front penetrates ~52 Å below the (001) surface after 21 days of dry O2 gas exposure at ambient pressure and temperature. X-ray photoelectron spectroscopy indicates U is present as U(IV), U(V), and U(VI).« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Koumetz, Serge D., E-mail: Serge.Koumetz@univ-rouen.fr; Martin, Patrick; Murray, Hugues
Experimental results on the diffusion of grown-in beryllium (Be) in indium gallium arsenide (In{sub 0.53}Ga{sub 0.47}As) and indium gallium arsenide phosphide (In{sub 0.73}Ga{sub 0.27}As{sub 0.58}P{sub 0.42}) gas source molecular beam epitaxy alloys lattice-matched to indium phosphide (InP) can be successfully explained in terms of a combined kick-out and dissociative diffusion mechanism, involving neutral Be interstitials (Be{sub i}{sup 0}), singly positively charged gallium (Ga), indium (In) self-interstitials (I{sub III}{sup +}) and singly positively charged Ga, In vacancies (V{sub III}{sup +}). A new numerical method of solution to the system of diffusion equations, based on the finite difference approximations and Bairstow's method,more » is proposed.« less
Diffuse Parenchymal Diseases Associated With Aluminum Use and Primary Aluminum Production
2014-01-01
Aluminum use and primary aluminum production results in the generation of various particles, fumes, gases, and airborne materials with the potential for inducing a wide range of lung pathology. Nevertheless, the presence of diffuse parenchymal or interstitial lung disease related to these processes remains controversial. The relatively uncommon occurrence of interstitial lung diseases in aluminum-exposed workers—despite the extensive industrial use of aluminum—the potential for concurrent exposure to other fibrogenic fibers, and the previous use of inhaled aluminum powder for the prevention of silicosis without apparent adverse respiratory effects are some of the reasons for this continuing controversy. Specific aluminum-induced parenchymal diseases described in the literature, including existing evidence of interstitial lung diseases, associated with primary aluminum production are reviewed. PMID:24806728
Kinetics of oxygen interstitial injection and lattice exchange in rutile TiO{sub 2}
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gorai, Prashun; Hollister, Alice G.; Pangan-Okimoto, Kristine
2014-05-12
The existence of a facile surface pathway for generation of O interstitials (O{sub i}) in rutile that can facilitate annihilation of O undesirable vacancies has been demonstrated recently. Through isotopic self-diffusion experiments, the present work determines a value of approximately 1.8 eV for the activation energy of O{sub i} injection from TiO{sub 2} (110). The mean path length for O{sub i} diffusion decreases by nearly an order of magnitude upon adsorption of 0.1 monolayer of sulfur. Sulfur apparently inhibits the surface annihilation rate of Ti interstitials, lowering their bulk concentration and the corresponding catalytic effect they seem to exert upon O{submore » i} exchange with the lattice.« less
Microdefects and self-interstitial diffusion in crystalline silicon
NASA Astrophysics Data System (ADS)
Knowlton, William Barthelemy
In this thesis, a study is presented of D-defects and self-interstitial diffusion in silicon using Li ion (Lisp+) drifting in an electric field and transmission electron microscopy (TEM). Obstruction of Lisp+ drifting has been found in wafers from certain but not all FZ p-type Si. Incomplete Lisp+ drifting always occurs in the central region of the wafers. This work established that interstitial oxygen is not responsible for hindering Lisp+ drifting. The Osb i concentration was measured ({˜}2× 10sp{15}\\ cmsp{-3}) by local vibrational mode Fourier transform infrared spectroscopy and did not vary radially across the wafer. TEM was performed on a samples from the partially Lisp+ drifted area and compared to regions without D-defects. Precipitates were found only in the region containing D-defects that had partially Lisp+ drifted. This result indicates D-defects are responsible for the precipitation that halts the Lisp+ drift process. The precipitates were characterized using selected area diffraction (SAD) and image contrast analysis. The results suggested that the precipitates may cause stacking faults and their identity may be lithium silicides such as Lisb{21}Sisb5\\ and\\ Lisb{13}Sisb4. TEM revealed a decreasing distribution of Li precipitates as a function of Lisp+ drift depth along the growth direction. A preliminary model is presented that simulates Lisp+ drifting. The objective of the model is to incorporate the Li precipitate density distribution and Lisp+ drift depth to extract the size and capture cross-section of the D-defects. Nitrogen (N) doping has been shown to eliminate D-defects as measured by conventional techniques. However, Lisp+ drifting has shown that D-defects are indeed still present. Lisp+ drifting is able to detect D-defects at concentrations lower than conventional techniques. Lisp+ drifting and D-defects provide a useful means to study Si self-interstitial diffusion. The process modeling program SUPREM-IV was used to simulate the results of Si self-interstitial diffusion obtained from Lisp+ drifting experiments. Anomalous results from the Si self-interstitial diffusion experiments forced a re-examination of the possibility of thermal dissociation of D-defects. Thermal annealing experiments that were performed support this possibility. A review of the current literature illustrates the need for more research on the effects of thermal processing on FZ Si to understand the dissolution kinetics of D-defects.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, Shenyang; Joshi, Vineet; Lavender, Curt A.
Experiments showed that recrystallization dramatically speeds up the gas bubble swelling kinetics in metallic UMo fuels. In this work a recrystallization model is developed to study the effect of microstructures and radiation conditions on recrystallization kinetics. The model integrates the rate theory of intra-granular gas bubble and interstitial loop evolution and a phase field model of recrystallization zone evolution. A fast passage method is employed to describe one dimensional diffusion of interstitials which have diffusivity several order magnitude larger than that of the fission gas Xe. With the model, the effect of grain sizes on recrystallization kinetics is simulated.
[Clinical significance of levels of lung surfactant protein A in serum, in various lung diseases].
Abe, S; Honda, Y; Ando, M; Saita, N; Kida, K; Jinno, S; Kondo, A; Kuroki, Y; Akino, T
1995-11-01
To assess the utility of measuring lung surfactant protein A (SP-A) in serum, a newly developed SP-A kit (Teijin TDR-30) was used at four facilities to measure serum SP-A levels in patients with various lung diseases. Serum SP-A levels in healthy volunteers were 24.6 +/- 9.6 ng/ml (mean +/- SD). serum SP-A levels did not differ significantly between different age groups (thirties through seventies). A cut-off level of 43.8 ng/ml was calculated, based on the values of the healthy volunteers. The serum SP-A levels in patients with idiopathic interstitial pneumonia (IIP: 67.9 +/- 42.5 ng/ml), pulmonary alveolar proteinosis (PAP: 7.0 +/- 45.7 ng/ml), and collagen disease with interstitial pneumonia (CDIP: 55.3 +/- 37.9 ng/ml) were significantly higher than those in healthy volunteers. When calculated with the cut-off value stated above, the positive rate of diagnosis for IIP was 71.4%. SP-A levels correlated closely with the clinical course; SP-A levels rose significantly during exacerbations of IIP. Measurement of SP-A in serum is useful for the diagnosis of IIP, PAP, and CDIP, and for monitoring exacerbations of IIP.
Asbestos exposure increases the incidence of histologically confirmed usual interstitial pneumonia.
Kawabata, Yoshinori; Shimizu, Yoshihiko; Hoshi, Eishin; Murai, Kazumi; Kanauchi, Tetsu; Kurashima, Kazuyoshi; Sugita, Yutaka
2016-02-01
We hypothesized that asbestos exposure increases the incidence of macroscopically visible and histologically confirmed usual interstitial pneumonia (histological UIP). We retrospectively examined 1718 cases (1202 males; mean age 66.7 years) who underwent lobectomy for resection of pleuropulmonary tumours. Objective markers for asbestos exposure included: the presence of malignant pleural mesothelioma, the presence of pleural plaques (PPs) and asbestos bodies in the histological specimen. Risk factors for histological UIP were examined. Two separate groups were studied: 183 with asbestos exposure, and 239 with histological UIP. The 183 cases with asbestos exposure had higher rates of positive occupational history and histological UIP (31%) than the remaining 1535. Among the asbestos-exposed group, small numbers of asbestos bodies were found in histological specimens of 21 cases of histological UIP. PPs and asbestos bodies were more frequent in the 239 patients with histological UIP than in the remaining 1479 UIP-negative patients. Multivariate analysis showed that asbestos exposure, especially positivity for asbestos bodies, that does not meet the current criteria for asbestosis increases the risk of histological UIP (P < 0.0001). Asbestos exposure causes asbestosis and increases the incidence of histological UIP. © 2015 John Wiley & Sons Ltd.
Identification of Clinical Phenotypes in Idiopathic Interstitial Pneumonia with Pulmonary Emphysema.
Sato, Suguru; Tanino, Yoshinori; Misa, Kenichi; Fukuhara, Naoko; Nikaido, Takefumi; Uematsu, Manabu; Fukuhara, Atsuro; Wang, Xintao; Ishida, Takashi; Munakata, Mitsuru
2016-01-01
Objective Since the term "combined pulmonary fibrosis and emphysema" (CPFE) was first proposed, the co-existence of pulmonary fibrosis and pulmonary emphysema (PE) has drawn considerable attention. However, conflicting results on the clinical characteristics of patients with both pulmonary fibrosis and PE have been published because of the lack of an exact definition of CPFE. The goal of this study was thus to clarify the clinical characteristics and phenotypes of idiopathic interstitial pneumonia (IIP) with PE. Methods We retrospectively analyzed IIP patients who had been admitted to our hospital. Their chest high-resolution computed tomography images were classified into two groups according to the presence of PE. We then performed a cluster analysis to identify the phenotypes of IIP patients with PE. Results Forty-four (53.7%) out of 82 patients had at least mild emphysema in their bilateral lungs. The cluster analysis separated the IIP patients with PE into three clusters. The overall survival rate of one cluster that consisted of mainly idiopathic pulmonary fibrosis (IPF) patients was significantly worse than those of the other clusters. Conclusion Three different phenotypes can be identified in IIP patients with PE, and IPF with PE is a distinct clinical phenotype with a poor prognosis.
Hori, Yuichi; Nakahara, Shiro; Mine, Sohtaro; Anjo, Naofumi; Fujii, Akiko; Ueda, Yoshihiko; Taguchi, Isao
2016-12-01
A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3-4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.
NASA Astrophysics Data System (ADS)
Korfiatis, P.; Kalogeropoulou, C.; Daoussis, D.; Petsas, T.; Adonopoulos, A.; Costaridou, L.
2009-07-01
Delineation of lung fields in presence of diffuse lung diseases (DLPDs), such as interstitial pneumonias (IP), challenges segmentation algorithms. To deal with IP patterns affecting the lung border an automated image texture classification scheme is proposed. The proposed segmentation scheme is based on supervised texture classification between lung tissue (normal and abnormal) and surrounding tissue (pleura and thoracic wall) in the lung border region. This region is coarsely defined around an initial estimate of lung border, provided by means of Markov Radom Field modeling and morphological operations. Subsequently, a support vector machine classifier was trained to distinguish between the above two classes of tissue, using textural feature of gray scale and wavelet domains. 17 patients diagnosed with IP, secondary to connective tissue diseases were examined. Segmentation performance in terms of overlap was 0.924±0.021, and for shape differentiation mean, rms and maximum distance were 1.663±0.816, 2.334±1.574 and 8.0515±6.549 mm, respectively. An accurate, automated scheme is proposed for segmenting abnormal lung fields in HRC affected by IP
Sethmann, Ingo; Wendt-Nordahl, Gunnar; Knoll, Thomas; Enzmann, Frieder; Simon, Ludwig; Kleebe, Hans-Joachim
2017-06-01
Randall's plaques (RP) are preferred sites for the formation of calcium oxalate monohydrate (COM) kidney stones. However, although processes of interstitial calcium phosphate (CaP) plaque formation are not well understood, the potential of plaque microstructures as indicators of CaP precipitation conditions received only limited attention. We investigated RP-associated COM stones for structural details of the calcified tissues and microstructural features of plaque-stone interfaces as indicators of the initial processes of stone formation. Significantly increased CaP supersaturation can be expected for interstitial fluid, if reabsorbed ions from the tubular system continuously diffuse into the collagenous connective tissue. Densely packed, fine-grained CaP particles were found in dense textures of basement membranes while larger, laminated particles were scattered in coarse-meshed interstitial tissue, which we propose to be due to differential spatial confinements and restrictions of ion diffusion. Particle morphologies suggest an initial precipitation as metastable amorphous calcium phosphate (ACP). Morphologies and arrangements of first COM crystals at the RP-stone interface ranged from stacked euhedral platelets to skeletal morphologies and even porous, dendritic structures, indicating, in this order, increasing levels of COM supersaturation. Furthermore, these first COM crystals were often coated with CaP. On this basis, we propose that ions from CaP-supersaturated interstitial fluid may diffuse through porous RP into the urine, where a resulting local increase in COM supersaturation could trigger crystal nucleation and, hence, initiate stone formation. Ion-depleted fluid in persistent pores of initial COM layers may get replenished from interstitial fluid, leading to CaP precipitation in porous COM.
Idiopathic pulmonary fibrosis: evolving concepts.
Ryu, Jay H; Moua, Teng; Daniels, Craig E; Hartman, Thomas E; Yi, Eunhee S; Utz, James P; Limper, Andrew H
2014-08-01
Idiopathic pulmonary fibrosis (IPF) occurs predominantly in middle-aged and older adults and accounts for 20% to 30% of interstitial lung diseases. It is usually progressive, resulting in respiratory failure and death. Diagnostic criteria for IPF have evolved over the years, and IPF is currently defined as a disease characterized by the histopathologic pattern of usual interstitial pneumonia occurring in the absence of an identifiable cause of lung injury. Understanding of the pathogenesis of IPF has shifted away from chronic inflammation and toward dysregulated fibroproliferative repair in response to alveolar epithelial injury. Idiopathic pulmonary fibrosis is likely a heterogeneous disorder caused by various interactions between genetic components and environmental exposures. High-resolution computed tomography can be diagnostic in the presence of typical findings such as bilateral reticular opacities associated with traction bronchiectasis/bronchiolectasis in a predominantly basal and subpleural distribution, along with subpleural honeycombing. In other circumstances, a surgical lung biopsy may be needed. The clinical course of IPF can be unpredictable and may be punctuated by acute deteriorations (acute exacerbation). Although progress continues in unraveling the mechanisms of IPF, effective therapy has remained elusive. Thus, clinicians and patients need to reach informed decisions regarding management options including lung transplant. The findings in this review were based on a literature search of PubMed using the search terms idiopathic pulmonary fibrosis and usual interstitial pneumonia, limited to human studies in the English language published from January 1, 2000, through December 31, 2013, and supplemented by key references published before the year 2000. Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
Prediction of oxygen distribution in aortic valve leaflet considering diffusion and convection.
Wang, Ling; Korossis, Sotirios; Fisher, John; Ingham, Eileen; Jin, Zhongmin
2011-07-01
Oxygen supply and transport is an important consideration in the development of tissue engineered constructs. Previous studies from our group have focused on the effect of tissue thickness on the oxygen diffusion within a three-dimensional aortic valve leaflet model, and highlighted the necessity for additional transport mechanisms such as oxygen convection. The aims of this study were to investigate the effect of interstitial fluid flow within the aortic valve leaflet, induced by the cyclic loading of the leaflet, on oxygen transport. Indentation testing and finite element modelings were employed to derive the biphasic properties of the leaflet tissue. The biphasic properties were subsequently used in the computational modeling of oxygen convection in the leaflet, which was based on the effective interstitial fluid velocity and the tissue deformation. Subsequently, the oxygen profile was predicted within the valve leaflet model by solving the diffusion and convection equation simultaneously utilizing the finite difference method. The compression modulus (E) and hydraulic permeability were determined by adapting a finite element model to the experimental indentation test on valvular tissue, E = 0.05MPa, and k =2.0 mm4/Ns. Finite element model of oxygen convection in valvular tissue incorporating the predicted biphasic properties was developed and the interstitial fluid flow rate was calculated falling in range of 0.025-0.25 mm/s depending on the tissue depth. Oxygen distribution within valvular tissue was predicted using one-dimensional oxygen diffusion model taking into consider the interstitial fluid effect. It was found that convection did enhance the oxygen transport in valvular tissue by up to 68% increase in the minimum oxygen tension within the tissue, depending on the strain level of the tissue as reaction of the magnitude and frequencies of the cardiac loading. The effective interstitial fluid velocity was found to play an important role in enhancing the oxygen transport within the valve leaflet. Such an understanding is important in the development of valvular tissue engineered constructs.
Acute fibrinous and organising pneumonia.
Gonçalves, João Rocha; Marques, Ricardo; Serra, Paula; Cardoso, Leila
2017-09-07
Acute fibrinous and organising pneumonia (AFOP) is a rare histological pattern of interstitial lung disease. The authors describe a 60-year-old woman admitted to the hospital for sustained fever, presenting with an alveolar opacity on chest X-ray, with the presumed diagnosis of community-acquired pneumonia and the onset of antibiotics. Since serological results suggested that Legionella pneumophila was the infectious agent, she was discharged on levofloxacin. A week later, she was again admitted with fever. CT scan showed opacities with crescentic morphology and a central ground-glass area suggestive of cryptogenic organising pneumonia. Microbiological, serological and autoimmunity tests were negative. She underwent surgical lung biopsy that revealed inflammatory infiltrate, macrophage desquamation, fibroblasts proliferation and fibrin deposition in the alveolar spaces, consistent with AFOP. She started corticotherapy with good response. Disease relapsed after prednisolone discontinuation, 10 months later. Currently, the patient is on prednisolone 5 mg/day without clinical and radiological recurrence. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Specific features of defect and mass transport in concentrated fcc alloys
Osetsky, Yuri N.; Béland, Laurent K.; Stoller, Roger E.
2016-06-15
We report that diffusion and mass transport are basic properties that control materials performance, such as phase stability, solute decomposition and radiation tolerance. While understanding diffusion in dilute alloys is a mature field, concentrated alloys are much less studied. Here, atomic-scale diffusion and mass transport via vacancies and interstitial atoms are compared in fcc Ni, Fe and equiatomic Ni-Fe alloy. High temperature properties were determined using conventional molecular dynamics on the microsecond timescale, whereas the kinetic activation-relaxation (k-ART) approach was applied at low temperatures. The k-ART was also used to calculate transition states in the alloy and defect transport coefficients.more » The calculations reveal several specific features. For example, vacancy and interstitial defects migrate via different alloy components, diffusion is more sluggish in the alloy and, notably, mass transport in the concentrated alloy cannot be predicted on the basis of diffusion in its pure metal counterparts. Lastly, the percolation threshold for the defect diffusion in the alloy is discussed and it is suggested that this phenomenon depends on the properties and diffusion mechanisms of specific defects.« less
Expression of inducible nitric oxide synthase in spontaneous bovine bronchopneumonia.
Fligger, J M; Waldvogel, A S; Pfister, H; Jungi, T W
1999-09-01
The expression of inducible nitric oxide synthase (iNOS), major histocompatibility class II molecules (MHC-II), CD68, and the calcium-binding proteins S100A8 and S100A9 (also called MRP8 and MRP14, respectively) was assessed in lung tissues from cattle that succumbed to pneumonia. Expression patterns of these markers were related to the types of lung lesion. iNOS expression was only observed in lungs infected with Arcanobacterium pyogenes or Pasteurella haemolytica but not in lungs from cattle with subacute chronic interstitial pneumonia and acute interstitial pneumonia due to Escherichia coli infection. High levels of iNOS were expressed by cells (probably leukocytes) surrounding necrotic foci. Occasionally, iNOS was expressed by intraalveolar macrophages in viable parenchyma, by leukocytes within the airways, and by some chondrocytes in the supporting cartilage of bronchi. Cells expressing MHC-II were distributed relatively evenly throughout areas of inflammation and did not display any clear association with necrotic foci. Cell types expressing MHC-II included type II alveolar epithelial cells, spindle-shaped cells of the interstitium, cells in bronchus-associated lymphoid tissue, and leukocytes in lymph and blood vessels but largely excluded iNOS-positive cells. Likewise, CD68-positive cells were rarely positive for iNOS and were not confined to the areas surrounding necrotic tissue. As with MHC-II and CD68, there was little if any coexpression of iNOS and either of the S100 proteins tested. Thus, in cattle with necrotizing bronchopneumonia, iNOS-expressing cells were largely restricted to the cellular zone surrounding necrotic areas.
Predicting vacancy-mediated diffusion of interstitial solutes in α -Fe
NASA Astrophysics Data System (ADS)
Barouh, Caroline; Schuler, Thomas; Fu, Chu-Chun; Jourdan, Thomas
2015-09-01
Based on a systematic first-principles study, the lowest-energy migration mechanisms and barriers for small vacancy-solute clusters (VnXm ) are determined in α -Fe for carbon, nitrogen, and oxygen, which are the most frequent interstitial solutes in several transition metals. We show that the dominant clusters present at thermal equilibrium (V X and V X2 ) have very reduced mobility compared to isolated solutes, while clusters composed of a solute bound to a small vacancy cluster may be significantly more mobile. In particular, V3X is found to be the fastest cluster for all three solutes. This result relies on the large diffusivity of the most compact trivacancy in a bcc lattice. Therefore, it may also be expected for interstitial solutes in other bcc metals. In the case of iron, we find that V3X may be as fast as or even more mobile than an interstitial solute. At variance with common assumptions, the trapping of interstitial solutes by vacancies does not necessarily decrease the mobility of the solute. Additionally, cluster dynamics simulations are performed considering a simple iron system with supersaturation of vacancies, in order to investigate the impacts of small mobile vacancy-solute clusters on properties such as the transport of solute and the cluster size distributions.
Near-infrared fiber delivery systems for interstitial photothermal therapy
NASA Astrophysics Data System (ADS)
Slatkine, Michael; Mead, Douglass S.; Konwitz, Eli; Rosenberg, Zvi
1995-05-01
Interstitial photothermal coagulation has long been recognized as a potential important, minimally invasive modality for treating a variety of pathologic conditions. We present two different technologies for interstitial photothermal coagulation of tissue with infrared lasers: An optical fiber with a radially symmetric diffusing tip for deep coagulation, and a flat bare fiber for the coagulation of thin and long lesions by longitudinally moving the fiber while lasing in concert. Urology and Gynecology Fibers: The fibers are 600 microns diameter with 20 - 40 mm frosted distal tips protected by a smooth transparent cover. When used with a Neodymium:YAG (Nd:YAG) laser, the active fiber surface diffuses optical radiation in a radial pattern, delivering up to 40 W power, and thus providing consistent and uniform interstitial photothermal therapy. Coagulation depth ranges from 4 to 15 mm. Animal studies in the United States and clinical studies in Europe have demonstrated the feasibility of using these fibers to treat benign prostatic hyperplasia and endometrial coagulation. Rhinology Fiber: The fiber is an 800 micron diameter flat fiber operated at 8 W power level while being interstitially pushed and pulled along its axis. A long and thin coagulated zone is produced. The fiber is routinely used for the shrinking of hypertrophic turbinates without surrounding and bone mucusal damage in ambulatory environments.
Pathogenesis of Idiopathic Pulmonary Fibrosis
Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.
2014-01-01
Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627
DOE Office of Scientific and Technical Information (OSTI.GOV)
Riise, Heine Nygard, E-mail: h.n.riise@fys.uio.no; Azarov, Alexander; Svensson, Bengt G.
2015-07-13
Shallow, Boron (B)-doped p{sup +} emitters have been realized using spin-on deposition and Flash Lamp Annealing (FLA) to diffuse B into monocrystalline float zone Silicon (Si). The emitters extend between 50 and 140 nm in depth below the surface, have peak concentrations between 9 × 10{sup 19 }cm{sup –3} and 3 × 10{sup 20 }cm{sup –3}, and exhibit sheet resistances between 70 and 3000 Ω/□. An exceptionally large increase in B diffusion occurs for FLA energy densities exceeding ∼93 J/cm{sup 2} irrespective of 10 or 20 ms pulse duration. The effect is attributed to enhanced diffusion of B caused by Si interstitial injection following a thermally activated reaction betweenmore » the spin-on diffusant film and the silicon wafer.« less
Carbon diffusion in bulk hcp zirconium: A multi-scale approach
NASA Astrophysics Data System (ADS)
Xu, Y.; Roques, J.; Domain, C.; Simoni, E.
2016-05-01
In the framework of the geological repository of the used fuel claddings of pressurized water reactor, carbon behavior in bulk zirconium is studied by periodic Density Functional Theory calculations. The C interstitial sites were investigated and it was found that there are two possible carbon interstitial sites: a distorted basal tetragonal site and an octahedral site. There are four types of possible atomic jumps between them. After calculating the migration energies, the attempt frequencies and the jump probabilities for each possible migration path, kinetic Monte Carlo (KMC) simulations were performed to simulate carbon diffusion at the macroscopic scale. The results show that carbon diffusion in pure Zr bulk is extremely limited at the storage temperature (50 °C). Since there are defects in Zr bulk, in a second step, the effect of atomic vacancy was studied and it was proved that vacancies cannot increase carbon diffusion.
First principles study of intrinsic defects in hexagonal tungsten carbide
NASA Astrophysics Data System (ADS)
Kong, Xiang-Shan; You, Yu-Wei; Xia, J. H.; Liu, C. S.; Fang, Q. F.; Luo, G.-N.; Huang, Qun-Ying
2010-11-01
The characteristics of intrinsic defects are important for the understanding of self-diffusion processes, mechanical strength, brittleness, and plasticity of tungsten carbide, which are present in the divertor of fusion reactors. Here, we use first-principles calculations to investigate the stability of point defects and their complexes in tungsten carbide. Our results confirm that the defect formation energies of carbon are much lower than that of tungsten and reveal the carbon vacancy to be the dominant defect in tungsten carbide. The C sbnd C dimer configuration along the dense a direction is the most stable configuration of carbon interstitial defect. The results of carbon defect diffusion show that the carbon vacancy stay for a wide range of temperature because of extremely high diffusion barriers, while carbon interstitial migration is activated at lower temperatures for its considerably lower activation energy. Both of them prefer to diffusion in carbon basal plane.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Andersson, Anders D.; Tonks, Michael R.; Casillas, Luis
2014-10-31
In light water reactor fuel, gaseous fission products segregate to grain boundaries, resulting in the nucleation and growth of large intergranular fission gas bubbles. Based on the mechanisms established from density functional theory (DFT) and empirical potential calculations 1, continuum models for diffusion of xenon (Xe), uranium (U) vacancies and U interstitials in UO 2 have been derived for both intrinsic conditions and under irradiation. Segregation of Xe to grain boundaries is described by combining the bulk diffusion model with a model for the interaction between Xe atoms and three different grain boundaries in UO 2 ( Σ5 tilt, Σ5more » twist and a high angle random boundary),as derived from atomistic calculations. All models are implemented in the MARMOT phase field code, which is used to calculate effective Xe and U diffusivities as well as redistribution for a few simple microstructures.« less
Pulmonary effects of synthetic marijuana: chest radiography and CT findings.
Berkowitz, Eugene A; Henry, Travis S; Veeraraghavan, Srihari; Staton, Gerald W; Gal, Anthony A
2015-04-01
The purpose of this article is to present the first chest radiographic and CT descriptions of organizing pneumonia in response to smoking synthetic marijuana. Chest radiographs showed a diffuse miliary-micronodular pattern. Chest CT images showed diffuse centrilobular nodules and tree-in-bud pattern and a histopathologic pattern of organizing pneumonia with or without patchy acute alveolar damage. This distinct imaging pattern should alert radiologists to include synthetic marijuana abuse in the differential diagnosis.
Gyulassy, Attila; Knoll, Aaron; Lau, Kah Chun; Wang, Bei; Bremer, Peer-Timo; Papka, Michael E; Curtiss, Larry A; Pascucci, Valerio
2016-01-01
Large-scale molecular dynamics (MD) simulations are commonly used for simulating the synthesis and ion diffusion of battery materials. A good battery anode material is determined by its capacity to store ion or other diffusers. However, modeling of ion diffusion dynamics and transport properties at large length and long time scales would be impossible with current MD codes. To analyze the fundamental properties of these materials, therefore, we turn to geometric and topological analysis of their structure. In this paper, we apply a novel technique inspired by discrete Morse theory to the Delaunay triangulation of the simulated geometry of a thermally annealed carbon nanosphere. We utilize our computed structures to drive further geometric analysis to extract the interstitial diffusion structure as a single mesh. Our results provide a new approach to analyze the geometry of the simulated carbon nanosphere, and new insights into the role of carbon defect size and distribution in determining the charge capacity and charge dynamics of these carbon based battery materials.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gyulassy, Attila; Knoll, Aaron; Lau, Kah Chun
2016-01-01
Large-scale molecular dynamics (MD) simulations are commonly used for simulating the synthesis and ion diffusion of battery materials. A good battery anode material is determined by its capacity to store ion or other diffusers. However, modeling of ion diffusion dynamics and transport properties at large length and long time scales would be impossible with current MD codes. To analyze the fundamental properties of these materials, therefore, we turn to geometric and topological analysis of their structure. In this paper, we apply a novel technique inspired by discrete Morse theory to the Delaunay triangulation of the simulated geometry of a thermallymore » annealed carbon nanosphere. We utilize our computed structures to drive further geometric analysis to extract the interstitial diffusion structure as a single mesh. Our results provide a new approach to analyze the geometry of the simulated carbon nanosphere, and new insights into the role of carbon defect size and distribution in determining the charge capacity and charge dynamics of these carbon based battery materials.« less
Gyulassy, Attila; Knoll, Aaron; Lau, Kah Chun; ...
2016-01-31
Large-scale molecular dynamics (MD) simulations are commonly used for simulating the synthesis and ion diffusion of battery materials. A good battery anode material is determined by its capacity to store ion or other diffusers. However, modeling of ion diffusion dynamics and transport properties at large length and long time scales would be impossible with current MD codes. To analyze the fundamental properties of these materials, therefore, we turn to geometric and topological analysis of their structure. In this paper, we apply a novel technique inspired by discrete Morse theory to the Delaunay triangulation of the simulated geometry of a thermallymore » annealed carbon nanosphere. We utilize our computed structures to drive further geometric analysis to extract the interstitial diffusion structure as a single mesh. Lastly, our results provide a new approach to analyze the geometry of the simulated carbon nanosphere, and new insights into the role of carbon defect size and distribution in determining the charge capacity and charge dynamics of these carbon based battery materials.« less
Trochet, Mickaël; Béland, Laurent Karim; Joly, Jean -François; ...
2015-06-16
We study point-defect diffusion in crystalline silicon using the kinetic activation-relaxation technique (k-ART), an off-lattice kinetic Monte Carlo method with on-the-fly catalog building capabilities based on the activation-relaxation technique (ART nouveau), coupled to the standard Stillinger-Weber potential. We focus more particularly on the evolution of crystalline cells with one to four vacancies and one to four interstitials in order to provide a detailed picture of both the atomistic diffusion mechanisms and overall kinetics. We show formation energies, activation barriers for the ground state of all eight systems, and migration barriers for those systems that diffuse. Additionally, we characterize diffusion pathsmore » and special configurations such as dumbbell complex, di-interstitial (IV-pair+2I) superdiffuser, tetrahedral vacancy complex, and more. In conclusion, this study points to an unsuspected dynamical richness even for this apparently simple system that can only be uncovered by exhaustive and systematic approaches such as the kinetic activation-relaxation technique.« less
Direct evidence of the recombination of silicon interstitial atoms at the silicon surface
NASA Astrophysics Data System (ADS)
Lamrani, Y.; Cristiano, F.; Colombeau, B.; Scheid, E.; Calvo, P.; Schäfer, H.; Claverie, Alain
2004-02-01
In this experiment, a Si wafer containing four lightly doped B marker layers epitaxially grown by CVD has been implanted with 100 keV Si + ions to a dose of 2 × 10 14 ions/cm 2 and annealed at 850 °C for several times in an RTA system in flowing N 2. TEM and SIMS analysis, in conjunction with a transient enhanced diffusion (TED) evaluation method based on the kick-out diffusion mechanism, have allowed us to accurately study the boron TED evolution in presence of extended defects. We show that the silicon surface plays a key role in the recombination of Si interstitial atoms by providing the first experimental evidence of the resulting Si ints supersaturation gradient between the defect region and the surface. Our results indicate an upper limit of about 200 nm for the surface recombination length of Si interstitials at 850 °C in a N 2 ambient.
Experimental and theoretical comparison of Sb, As, and P diffusion mechanisms and doping in CdTe
NASA Astrophysics Data System (ADS)
Colegrove, E.; Yang, J.-H.; Harvey, S. P.; Young, M. R.; Burst, J. M.; Duenow, J. N.; Albin, D. S.; Wei, S.-H.; Metzger, W. K.
2018-02-01
Fundamental material doping challenges have limited CdTe electro-optical applications. In this work, the As atomistic diffusion mechanisms in CdTe are examined by spatially resolving dopant incorporation in both single-crystalline and polycrystalline CdTe over a range of experimental conditions. Density-functional theory calculations predict experimental activation energies and indicate that As diffuses slowly through the Te sublattice and quickly along GBs similar to Sb. Because of its atomic size and associated defect chemistry, As does not have a fast interstitial diffusion component similar to P. Experiments to incorporate and activate P, As, and Sb in polycrystalline CdTe are conducted to examine if ex situ Group V doping can overcome historic polycrystalline doping limits. The distinct P, As, and Sb diffusion characteristics create different strategies for increasing hole density. Because fast interstitial diffusion is prominent for P, less aggressive diffusion conditions followed by Cd overpressure to relocate the Group V element to the Te lattice site is effective. For larger atoms, slower diffusion through the Te sublattice requires more aggressive diffusion, however further activation is not always necessary. Based on the new physical understanding, we have obtained greater than 1016 cm-3 hole density in polycrystalline CdTe films by As and P diffusion.
Experimental and theoretical comparison of Sb, As, and P diffusion mechanisms and doping in CdTe
DOE Office of Scientific and Technical Information (OSTI.GOV)
Colegrove, E.; Yang, J-H; Harvey, S. P.
Fundamental material doping challenges have limited CdTe electro-optical applications. In this work, the As atomistic diffusion mechanisms in CdTe are examined by spatially resolving dopant incorporation in both single-crystalline and polycrystalline CdTe over a range of experimental conditions. Density-functional theory calculations predict experimental activation energies and indicate As diffuses slowly through the Te sublattice and quickly along GBs similar to Sb. Because of its atomic size and associated defect chemistry, As does not have a fast interstitial diffusion component similar to P. Experiments to incorporate and activate P, As, and Sb in polycrystalline CdTe are conducted to examine if ex-situmore » Group V doping can overcome historic polycrystalline doping limits. The distinct P, As, and Sb diffusion characteristics create different strategies for increasing hole density. Because fast interstitial diffusion is prominent for P, less aggressive diffusion conditions followed by Cd overpressure to relocate the Group V element to the Te lattice site is effective. For larger atoms, slower diffusion through the Te sublattice requires more aggressive diffusion, however further activation is not always necessary. Based on the new physical understanding, we have obtained greater than 10^16 cm^-3 hole density in polycrystalline CdTe films by As and P diffusion.« less
Experimental and theoretical comparison of Sb, As, and P diffusion mechanisms and doping in CdTe
Colegrove, E.; Yang, J-H; Harvey, S. P.; ...
2018-01-29
Fundamental material doping challenges have limited CdTe electro-optical applications. In this work, the As atomistic diffusion mechanisms in CdTe are examined by spatially resolving dopant incorporation in both single-crystalline and polycrystalline CdTe over a range of experimental conditions. Density-functional theory calculations predict experimental activation energies and indicate As diffuses slowly through the Te sublattice and quickly along GBs similar to Sb. Because of its atomic size and associated defect chemistry, As does not have a fast interstitial diffusion component similar to P. Experiments to incorporate and activate P, As, and Sb in polycrystalline CdTe are conducted to examine if ex-situmore » Group V doping can overcome historic polycrystalline doping limits. The distinct P, As, and Sb diffusion characteristics create different strategies for increasing hole density. Because fast interstitial diffusion is prominent for P, less aggressive diffusion conditions followed by Cd overpressure to relocate the Group V element to the Te lattice site is effective. For larger atoms, slower diffusion through the Te sublattice requires more aggressive diffusion, however further activation is not always necessary. Based on the new physical understanding, we have obtained greater than 10^16 cm^-3 hole density in polycrystalline CdTe films by As and P diffusion.« less
Molecular dynamics simulations of the diffusion and coalescence of helium in tungsten
NASA Astrophysics Data System (ADS)
Zhou, Y. L.; Wang, J.; Hou, Q.; Deng, A. H.
2014-03-01
Molecular dynamics (MD) simulations are performed on the diffusion and coalescence of helium in tungsten. A new method for determining the effective capture radii (ECRs) and the dissociation energies of helium-related defects is proposed in this work. It is observed that the ECR of an interstitial helium atom trapping helium interstitials (denoted as He-Hen, n = 1-3) decreases with increasing temperature, except for He-He2 at T < 400 K. The traditional view that the ECR is approximately equal to the lattice constant, which has been widely used in kinetic Monte Carlo (KMC) and rate theory (RT) models, is only valid in some cases. However, the ECR between an interstitial helium atom and a substitutional helium atom (denoted as He-HeV) always approximates the third nearest-neighbor tetrahedral positions of the HeV. The diffusion coefficients Dn for helium clusters are also investigated. He2 migrates more quickly than a single He atom does at T < 400 K, whereas the diffusion path of He2 changes at higher temperatures. Another counterintuitive observation is that D5 > D3 > D4 at T < 500 K, which can be attributed to the disordered structure of He5. The Arrhenius relation describes the diffusion of Hen well in the temperature range from 300 K to 550 K, whereas the diffusion is not a standard thermally activated process at higher temperatures. Taken together, these results help elucidate the initial stage of helium bubble formation in tungsten as well as the requirements of long-term evolution methods such as KMC or RT models.
New insights into canted spiro carbon interstitial in graphite
NASA Astrophysics Data System (ADS)
EL-Barbary, A. A.
2017-12-01
The self-interstitial carbon is the key to radiation damage in graphite moderator nuclear reactor, so an understanding of its behavior is essential for plant safety and maximized reactor lifetime. The density functional theory is applied on four different graphite unit cells, starting from of 64 carbon atoms up to 256 carbon atoms, using AIMPRO code to obtain the energetic, athermal and mechanical properties of carbon interstitial in graphite. This study presents first principles calculations of the energy of formation that prove its high barrier to athermal diffusion (1.1 eV) and the consequent large critical shear stress (39 eV-50 eV) necessary to shear graphite planes in its presence. Also, for the first time, the gamma surface of graphite in two dimensions is calculated and found to yield the critical shear stress for perfect graphite. Finally, in contrast to the extensive literature describing the interstitial of carbon in graphite as spiro interstitial, in this work the ground state of interstitial carbon is found to be canted spiro interstitial.
Interstitial fluid flow and drug delivery in vascularized tumors: a computational model.
Welter, Michael; Rieger, Heiko
2013-01-01
Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider-with the help of a theoretical model-the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells.
Alpha-particle radiotherapy: For large solid tumors diffusion trumps targeting.
Zhu, Charles; Sempkowski, Michelle; Holleran, Timothy; Linz, Thomas; Bertalan, Thomas; Josefsson, Anders; Bruchertseifer, Frank; Morgenstern, Alfred; Sofou, Stavroula
2017-06-01
Diffusion limitations on the penetration of nanocarriers in solid tumors hamper their therapeutic use when labeled with α-particle emitters. This is mostly due to the α-particles' relatively short range (≤100 μm) resulting in partial tumor irradiation and limited killing. To utilize the high therapeutic potential of α-particles against solid tumors, we designed non-targeted, non-internalizing nanometer-sized tunable carriers (pH-tunable liposomes) that are triggered to release, within the slightly acidic tumor interstitium, highly-diffusive forms of the encapsulated α-particle generator Actinium-225 ( 225 Ac) resulting in more homogeneous distributions of the α-particle emitters, improving uniformity in tumor irradiation and increasing killing efficacies. On large multicellular spheroids (400 μm-in-diameter), used as surrogates of the avascular areas of solid tumors, interstitially-releasing liposomes resulted in best growth control independent of HER2 expression followed in performance by (a) the HER2-targeting radiolabeled antibody or (b) the non-responsive liposomes. In an orthotopic human HER2-negative mouse model, interstitially-releasing 225 Ac-loaded liposomes resulted in the longest overall and median survival. This study demonstrates the therapeutic potential of a general strategy to bypass the diffusion-limited transport of radionuclide carriers in solid tumors enabling interstitial release from non-internalizing nanocarriers of highly-diffusing and deeper tumor-penetrating molecular forms of α-particle emitters, independent of cell-targeting. Copyright © 2017 Elsevier Ltd. All rights reserved.
Coverdill, Christopher C; Barnes, Julie A; Garner, Michael M; Hinton, Kevin L; Childress, April L; Wellehan, James F X
2016-05-01
A novel herpesvirus was detected in a 17-day-old Chilean flamingo (Phoenicopterus chilensis) with pneumonia, hepatopathy, and severe anemia that was housed in California. Postmortem examination identified a pale, enlarged liver, mildly increased fluid in the lungs, and red foci in the spleen. Histologic examination revealed marked hepatic necrosis with syncytia, splenic necrosis, and interstitial pneumonia with eosinophilic intranuclear inclusions within hepatocytes and in unidentified cells of the lung. Transmission electron microscopy identified virions consistent with a herpesvirus in the nucleus and cytoplasm of degenerative hepatocytes. Nested consensus PCR, sequencing, and phylogenetic analysis identified a novel herpesvirus within the genus Iltovirus in the subfamily Alphaherpesvirinae. © 2016 The Author(s).
Lipid-derived free radical production in superantigen-induced interstitial pneumonia
Miyakawa, Hisako; Mason, Ronald P.; Jiang, JinJie; Kadiiska, Maria B.
2009-01-01
We studied the free radical generation involved in the development of interstitial pneumonia (IP) in an animal model of autoimmune disease. We observed an electron spin resonance (ESR) spectrum of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) radical adducts detected in the lipid extract of lungs in autoimmune-prone mice after intratracheal instillation of staphylococcal enterotoxin B. The POBN adducts detected by ESR were paralleled by infiltration of macrophages and neutrophils in the bronchoalveolar lavage fluid. To further investigate the mechanism of free radical generation, mice were pretreated with the macrophage toxicant gadolinium chloride, which significantly suppressed the radical generation. Free radical generation was also decreased by pretreatment with the xanthine oxidase (XO) inhibitor allopurinol, the iron chelator Desferal, and the inducible nitric oxide synthase (iNOS) inhibitor 1400W. Histopathologically, these drugs significantly reduced both the cell infiltration to alveolar septal walls and the synthesis of pulmonary collagen fibers. Experiments with NADPH oxidase knockout mice showed that NADPH oxidase did not contribute to lipid radical generation. These results suggest that lipid-derived carbon-centered free radical production is important in the manifestation of IP and that a macrophage toxicant, an XO inhibitor, an iron chelator, and an iNOS inhibitor protect against both radical generation and the manifestation of IP. PMID:19376221
NASA Astrophysics Data System (ADS)
Fetita, C.; Chang-Chien, K. C.; Brillet, P. Y.; Pr"teux, F.; Chang, R. F.
2012-03-01
Our study aims at developing a computer-aided diagnosis (CAD) system for fully automatic detection and classification of pathological lung parenchyma patterns in idiopathic interstitial pneumonias (IIP) and emphysema using multi-detector computed tomography (MDCT). The proposed CAD system is based on three-dimensional (3-D) mathematical morphology, texture and fuzzy logic analysis, and can be divided into four stages: (1) a multi-resolution decomposition scheme based on a 3-D morphological filter was exploited to discriminate the lung region patterns at different analysis scales. (2) An additional spatial lung partitioning based on the lung tissue texture was introduced to reinforce the spatial separation between patterns extracted at the same resolution level in the decomposition pyramid. Then, (3) a hierarchic tree structure was exploited to describe the relationship between patterns at different resolution levels, and for each pattern, six fuzzy membership functions were established for assigning a probability of association with a normal tissue or a pathological target. Finally, (4) a decision step exploiting the fuzzy-logic assignments selects the target class of each lung pattern among the following categories: normal (N), emphysema (EM), fibrosis/honeycombing (FHC), and ground glass (GDG). According to a preliminary evaluation on an extended database, the proposed method can overcome the drawbacks of a previously developed approach and achieve higher sensitivity and specificity.
Pleuroparenchymal fibroelastosis: is it also an idiopathic entity?
Portillo, Karina; Guasch Arriaga, Ignasi; Ruiz-Manzano, Juan
2015-10-01
Pleuroparenchymal fibroelastosis (PPFE) is a rare disease that has been recently included in the updated consensus on idiopathic interstitial pneumonias. It shares some clinical features with other chronic interstitial pneumonias (dyspnea, dry cough), and is radiologically characterized by pleural and subpleural parenchymal fibrosis and elastosis, mainly in the upper lobes. The main histological findings include pleural fibrosis and prominent subpleural and parenchymal fibroelastosis. Its characterization is based on the increasing number of cases reported in the literature, so several aspects of the etiology, pathogenesis and natural history are still unknown. Although some cases have been described as idiopathic, PPFE has been reported as a complication after bone marrow transplantation, lung transplantation and chemotherapy, especially with alkylating agents.Spontaneous or iatrogenic pneumothorax is a frequently reported complication of invasive diagnostic tests for identifying PPFE. The disease course is variable, ranging from slow progression to rapid clinical deterioration. No treatment has shown evidence of efficacy, and lung transplantation remains the only option for patients who fulfill the diagnostic criteria for this option. Recognizing and disseminating the specific features of PPFE is essential to raise the level of clinical suspicion for this entity, and to implement appropriate multidisciplinary diagnostic management. Copyright © 2015 SEPAR. Published by Elsevier Espana. All rights reserved.
Kotani, Toru; Katayama, Shinshu; Miyazaki, Yuya; Fukuda, Satoshi; Sato, Yoko; Ohsugi, Koichi
2017-01-01
The risk factors for the mortality rate of Pneumocystis jirovecii pneumonia (PCP) who required mechanical ventilation (MV) remained unknown. A retrospective chart review was performed of all PCP patients admitted to our intensive care unit and treated for acute hypoxemic respiratory failure to assess the risk factors for the high mortality. Twenty patients without human immunodeficiency virus infection required mechanical ventilation; 19 received noninvasive ventilation; and 11 were intubated. PEEP was incrementally increased and titrated to maintain FIO 2 as low as possible. No mandatory ventilation was used. Sixteen patients (80%) survived. Pneumothorax developed in one patient with rheumatoid arthritis (RA). Median PEEP level in the first 5 days was 10.0 cmH 2 O and not associated with death. Multivariate analysis showed the association of incidence of interstitial lung disease and increase in serum KL-6 with 90-day mortality. We found MV strategies to prevent pneumothorax including liberal use of noninvasive ventilation, and PEEP titration and disuse of mandatory ventilation may improve mortality in this setting. Underlying disease of interstitial lung disease was a risk factor and KL-6 may be a useful predictor associated with mortality in patients with RA. These findings will need to be validated in larger studies.
Substitutional and Interstitial Diffusion in alpha2-Ti3Al(O)
NASA Technical Reports Server (NTRS)
Copland, Evan; Young, David J.; Gleeson, Brian; Jacobson, Nathan
2007-01-01
The reaction between Al2O3 and alpha2-Ti3Al was studied with a series of Al2O3/alpha2-Ti3Al multiphase diffusion couples annealed at 900, 1000 and 1100 C. The diffusion-paths were found to strongly depend on alpha2- Ti3Al(O) composition. For alloys with low oxygen concentrations the reaction involved the reduction of Al2O3, the formation of a gamma-TiAl reaction-layer and diffusion of Al and O into the alpha2-Ti3Al substrate. Measured concentration profiles across the interaction-zone showed "up-hill" diffusion of O in alpha2-Ti3Al(O) indicating a significant thermodynamic interaction between O and Al, Ti or both. Diffusion coefficients for the interstitial O in alpha2-Ti3Al(O) were determined independently from the interdiffusion of Ti and Al on the substitutional lattice. Diffusion coefficients are reported for alpha2-Ti3Al(O) as well as gamma-TiAl. Interpretation of the results were aided with the subsequent measurement of the activities of Al, Ti and O in alpha 2-Ti3Al(O) by Knudsen effusion-cell mass spectrometry.
Takada, Toshinori; Moriyama, Hiroshi; Suzuki, Eiichi
2014-01-01
Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases. Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Walsh, Simon L F; Wells, Athol U; Desai, Sujal R; Poletti, Venerino; Piciucchi, Sara; Dubini, Alessandra; Nunes, Hilario; Valeyre, Dominique; Brillet, Pierre Y; Kambouchner, Marianne; Morais, António; Pereira, José M; Moura, Conceição Souto; Grutters, Jan C; van den Heuvel, Daniel A; van Es, Hendrik W; van Oosterhout, Matthijs F; Seldenrijk, Cornelis A; Bendstrup, Elisabeth; Rasmussen, Finn; Madsen, Line B; Gooptu, Bibek; Pomplun, Sabine; Taniguchi, Hiroyuki; Fukuoka, Junya; Johkoh, Takeshi; Nicholson, Andrew G; Sayer, Charlie; Edmunds, Lilian; Jacob, Joseph; Kokosi, Maria A; Myers, Jeffrey L; Flaherty, Kevin R; Hansell, David M
2016-07-01
Diffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease. We did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis. 70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (κ=0·50). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (κw=0·71 [IQR 0·64-0·77]) and connective tissue disease-related interstitial lung disease (κw=0·73 [0·68-0·78]); moderate for non-specific interstitial pneumonia (NSIP; κw=0·42 [0·37-0·49]); and fair for hypersensitivity pneumonitis (κw=0·29 [0·24-0·40]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinician's diagnosis of this disease in five of seven MDTMs, and radiologist's diagnosis of IPF in four of seven MDTMs. Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease. National Institute of Health Research, Imperial College London. Copyright © 2016 Elsevier Ltd. All rights reserved.
Twenhafel, N A; Shaia, C I; Bunton, T E; Shamblin, J D; Wollen, S E; Pitt, L M; Sizemore, D R; Ogg, M M; Johnston, S C
2015-01-01
Eight guinea pigs were aerosolized with guinea pig-adapted Zaire ebolavirus (variant: Mayinga) and developed lethal interstitial pneumonia that was distinct from lesions described in guinea pigs challenged subcutaneously, nonhuman primates challenged by the aerosol route, and natural infection in humans. Guinea pigs succumbed with significant pathologic changes primarily restricted to the lungs. Intracytoplasmic inclusion bodies were observed in many alveolar macrophages. Perivasculitis was noted within the lungs. These changes are unlike those of documented subcutaneously challenged guinea pigs and aerosolized filoviral infections in nonhuman primates and human cases. Similar to findings in subcutaneously challenged guinea pigs, there were only mild lesions in the liver and spleen. To our knowledge, this is the first report of aerosol challenge of guinea pigs with guinea pig-adapted Zaire ebolavirus (variant: Mayinga). Before choosing this model for use in aerosolized ebolavirus studies, scientists and pathologists should be aware that aerosolized guinea pig-adapted Zaire ebolavirus (variant: Mayinga) causes lethal pneumonia in guinea pigs. © The Author(s) 2014.
Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi
2016-01-01
We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.
Barrier Coatings for Refractory Metals and Superalloys
DOE Office of Scientific and Technical Information (OSTI.GOV)
SM Sabol; BT Randall; JD Edington
2006-02-23
In the closed working fluid loop of the proposed Prometheus space nuclear power plant (SNPP), there is the potential for reaction of core and plant structural materials with gas phase impurities and gas phase transport of interstitial elements between superalloy and refractory metal alloy components during service. Primary concerns are surface oxidation, interstitial embrittlement of refractory metals and decarburization of superalloys. In parallel with kinetic investigations, this letter evaluates the ability of potential coatings to prevent or impede communication between reactor and plant components. Key coating requirements are identified and current technology coating materials are reviewed relative to these requirements.more » Candidate coatings are identified for future evaluation based on current knowledge of design parameters and anticipated environment. Coatings were identified for superalloys and refractory metals to provide diffusion barriers to interstitial transport and act as reactive barriers to potential oxidation. Due to their high stability at low oxygen potential, alumina formers are most promising for oxidation protection given the anticipated coolant gas chemistry. A sublayer of iridium is recommended to provide inherent diffusion resistance to interstitials. Based on specific base metal selection, a thin film substrate--coating interdiffusion barrier layer may be necessary to meet mission life.« less
Man, Sorin Claudiu; Fufezan, Otilia; Sas, Valentina; Schnell, Cristina
2017-05-10
The objective of the study was to assess the performance of lung ultrasonography (LUS) as compared to chest radiography and the clinical criteria for the diagnosis of pneumonia in children. This was a retrospective study in which data were collected from medical files of 81 children admitted with a clinical suspicion of pneumonia in which both an LUS and a chest radiograph during the hospitalization were performed. Reference standard used for the diagnosis of pneumonia were chest radiographs (consolidation, parenchymal infiltrates, and interstitial infiltrate) and clinical criteria. LUSfindings were reported as normal, parenchymal consolidations and pleural effusions. Radiological pneumonia was reported in 72 of the 81 patients (88.9%). LUS identified parenchymal consolidations in 62 cases. LUS correctly identified radiological pneumonia with a sensitivity of 79.2% and a specificity of 44.4%. The positive predictive value (PPV) was 91.9% and the negative predictive value (NPV) was 21.0%. When clinical criteria were used as reference standard, the sensitivity, specificity, PPV and NPV of correctly identifying clinical pneumonia cases by LUS (only consolidations) were 80.0%, 66.7%, 96.8% and 21.0%. When indicative for the presence of pneumonia either the ultrasound consolidation or the ultrasound detected pleural effusion were considered when the sensitivity, PPV and NPV increased to 96.0% (95%CI: 88.8-99.2), 97.3% (95%CI: 92.0-99.1), and 57.1% (95%CI: 27.7-82.2), respectively. In our opinion, our findings together withprevious ones available in the literature recommend LUS as a valuable investigation for the diagnosis of community-acquiredpneumonia in children.
Shimada, Kota; Yokosuka, Kyoko; Nunokawa, Takahiro; Sugii, Shoji
2018-06-06
To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma β-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm 3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.
Classification of diffuse lung diseases: why and how.
Hansell, David M
2013-09-01
The understanding of complex lung diseases, notably the idiopathic interstitial pneumonias and small airways diseases, owes as much to repeated attempts over the years to classify them as to any single conceptual breakthrough. One of the many benefits of a successful classification scheme is that it allows workers, within and between disciplines, to be clear that they are discussing the same disease. This may be of particular importance in the recruitment of individuals for a clinical trial that requires a standardized and homogeneous study population. Different specialties require fundamentally different things from a classification: for epidemiologic studies, a classification that requires categorization of individuals according to histopathologic pattern is not usually practicable. Conversely, a scheme that simply divides diffuse parenchymal disease into inflammatory and noninflammatory categories is unlikely to further the understanding about the pathogenesis of disease. Thus, for some disease groupings, for example, pulmonary vasculopathies, there may be several appropriate classifications, each with its merits and demerits. There has been an interesting shift in the past few years, from the accepted primacy of histopathology as the sole basis on which the classification of parenchymal lung disease has rested, to new ways of considering how these entities relate to each other. Some inventive thinking has resulted in new classifications that undoubtedly benefit patients and clinicians in their endeavor to improve management and outcome. The challenge of understanding the logic behind current classifications and their shortcomings are explored in various examples of lung diseases.
Pathogen characteristics reveal novel antibacterial approaches for interstitial lung disease.
Lu, Hai-Wen; Ji, Xiao-Bin; Liang, Shuo; Fan, Li-Chao; Bai, Jiu-Wu; Chen, Ke-Bing; Zhou, Yin; Li, Hui-Ping; Xu, Jin-Fu
2014-12-01
Interstitial lung disease (ILD) is a clinical disorder associated with changes of lung structure. Concurrent infection is a serious complication and one of the major factors that exacerbates ILD. Pathogen screening is a critical step in early diagnosis and proper treatment of ILD with secondary infection. Here we analyzed distribution and drug susceptibility of pathogens isolated from hospitalized ILD patients from January, 2007 to December, 2008 and compared them to bacterial drug resistance data in CHINET during the same period. The main specimens were from sputum culture, lavage fluid culture, lung biopsy tissue culture, and pleural effusion culture and bacterial or fungal cultures were performed on these specimens accordingly. Drug susceptibility was tested for positive bacterial cultures using disk diffusion (Kirby-Bauer method) and E Test strips in which results were determined based on the criteria of CLSI (2007). A total of 371 pathogen strains from ILD patients, including 306 bacterial strains and 65 fungal strains were isolated and cultured. Five main bacterial strains and their distribution were as follows: Klebsiella pneumoniae (31.7%), Pseudomonas aeruginosa (20.6%), Acinetobacter (12.7%), Enterobacter cloacae (8.2%), and Staphylococcus aureus (7.8%). The results showed that ILD patients who had anti-infection treatment tended to have Gram-negative bacteria, whether they acquired an infection in the hospital or elsewhere. Drug resistance screening indicated that aminoglycosides and carbapenems had lower antibiotic resistance rates. In addition, we found that the usage of immunosuppressants was associated with the increased infection rate and number of pathogens that were isolated. In conclusion, aminoglycosides and carbapenems may be selected as a priority for secondary infection to control ILD progression. Meanwhile, the use of anti-MRSA/MRCNS drugs may be considered for Staphylococcus infection. Copyright © 2014 Elsevier Ltd. All rights reserved.
Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki
2017-09-01
Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.
Dai, Jing-Hong; Li, Hui; Shen, Wei; Miao, Li-Yun; Xiao, Yong-Long; Huang, Mei; Cao, Meng-Shu; Wang, Yang; Zhu, Bin; Meng, Fan-Qing; Cai, Hou-Rong
2015-10-20
Acute fibrinous and organizing pneumonia (AFOP) is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia. It was divided into rare idiopathic interstitial pneumonia according to the classification notified by American Thoracic Society/European Respiratory Society in 2013. As a rare pathological entity, it is still not well known and recognized by clinicians. We reviewed the clinical features of 20 patients with AFOP diagnosed in a teaching hospital. The medical records of 20 patients with biopsy-proven diagnosis of AFOP were retrospectively reviewed. The patients' symptoms, duration of the disease, comorbidities, clinical laboratory data, pulmonary function testing, radiographic studies, and the response to treatment were extracted and analyzed. Fever was the most common symptom and was manifested in 90% of AFOP patients. For clinical laboratory findings, systematic inflammatory indicators, including C-reactive protein and erythrocyte sedimentation rate, were significantly higher than normal in AFOP patients. In accordance with this increased indicators, injured liver functions were common in AFOP patients. Inversely, AFOP patients had worse clinical conditions including anemia and hypoalbuminemia. For pulmonary function testing, AFOP patients showed the pattern of restrictive mixed with obstructive ventilation dysfunction. For high-resolution computerized tomography (HRCT) findings, the most common pattern for AFOP patients was lobar consolidation which was very similar to pneumonia. However, unlike pneumonia, AFOP patients responded well to glucocorticoids. Patients with AFOP manifest as acute inflammatory-like clinical laboratory parameters and lobar consolidation on HRCT, but respond well to steroid.
Lochindarat, Sorasak; Bunnag, Thanyanat
2011-08-01
A novel influenza A (H1N1) virus of swine origin caused human infection and acute respiratory illness in Mexico during the spring of 2009. After that, the virus spread globally, resulting in the influenza pandemic. To observe the clinical manifestations of the 2009 pandemic influenza A (H1N1) and the epidemic waves of hospitalized children for a period of one year. A prospective observational study of children under eighteen years old, confirmed having the 2009 pandemic influenza (H1N1) infection by real-time reverse-transcription-polymerase-chain-reaction (RT-PCR), admitted at Queen Sirikit National Institute of Child Health, Bangkok, Thailand during one year, from 1st June 2009 to 31st May 2010. A total of 83 pandemic influenza infected children were admitted during a one-year period. There were two waves of epidemic outbreak, the first wave from June to August 2009 and the second wave from January to February 2010. There were 47 cases of males (56.6%), with the highest attack rates among children 1-5 years of age (48.2%). The youngest case was a 29-day old girl. The correct provisional diagnosis of pandemic influenza infection are 39.5%, the other initial diagnosis are pneumonia, bronchiolitis, tonsillitis, encephalitis, and dengue infection. Most patients coming for care had typical, influenza-like symptoms with fever (98.8%), cough (92.6%) and rhinorrhea (74.1%). Systemic symptoms are frequent. Gastrointestinal symptoms (including vomiting (46.9%) and diarrhea (24.7%)) occur more commonly than seasonal influenza. Pneumonia is the most common complication (43.2%); other complications include bronchiolitis, hemoptysis, acute respiratory distress syndrome (ARDS) and encephalitis. In one case, a seven year old girl suffered from ARDS, sepsis, multi-organ dysfunction syndrome and ventilator associated pneumonia, but survived with some neurological sequelae. Radiographic findings included diffuse interstitial, alveolar infiltrates and some in lobar distributions. Apart from oseltamivir the other antibiotics included ceftriaxone, cefotaxime, amplicillin and azithromycin, were added for pneumonia. All patients in the present study survived. The burden and character of pandemic influenza infection in developing countries are still incompletely understood. Early therapy with oseltamivir in severely ill patients, without waiting for laboratory confirmation for diagnosis, will save patients from severe complications.
Rheumatoid Arthritis (RA) associated interstitial lung disease (ILD).
O'Dwyer, David N; Armstrong, Michelle E; Cooke, Gordon; Dodd, Jonathan D; Veale, Douglas J; Donnelly, Seamas C
2013-10-01
Rheumatoid Arthritis (RA) is the most common Connective Tissue Disease (CTD) and represents an increasing burden on global health resources. Interstitial lung disease (ILD) has been recognised as a complication of RA but its potential for mortality and morbidity has arguably been under appreciated for decades. New studies have underscored a significant lifetime risk of ILD development in RA. Contemporary work has identified an increased risk of mortality associated with the Usual Interstitial Pneumonia (UIP) pattern which shares similarity with the most devastating of the interstitial pulmonary diseases, namely Idiopathic Pulmonary Fibrosis (IPF). In this paper, we discuss recent studies highlighting the associated increase in mortality in RA-UIP. We explore associations between radiological and histopathological features of RA-ILD and the prognostic implications of same. We emphasise the need for translational research in this area given the growing burden of RA-ILD. We highlight the importance of the respiratory physician as a key stakeholder in the multidisciplinary management of this disorder. RA-ILD focused research offers the opportunity to identify early asymptomatic disease and define the natural history of this extra articular manifestation. This may provide a unique opportunity to define key regulatory fibrotic events driving progressive disease. We also discuss some of the more challenging and novel aspects of therapy for RA-ILD. © 2013.
Quantum statistical effects in the mass transport of interstitial solutes in a crystalline solid
NASA Astrophysics Data System (ADS)
Woo, C. H.; Wen, Haohua
2017-09-01
The impact of quantum statistics on the many-body dynamics of a crystalline solid at finite temperatures containing an interstitial solute atom (ISA) is investigated. The Mori-Zwanzig theory allows the many-body dynamics of the crystal to be formulated and solved analytically within a pseudo-one-particle approach using the Langevin equation with a quantum fluctuation-dissipation relation (FDR) based on the Debye model. At the same time, the many-body dynamics is also directly solved numerically via the molecular dynamics approach with a Langevin heat bath based on the quantum FDR. Both the analytical and numerical results consistently show that below the Debye temperature of the host lattice, quantum statistics significantly impacts the ISA transport properties, resulting in major departures from both the Arrhenius law of diffusion and the Einstein-Smoluchowski relation between the mobility and diffusivity. Indeed, we found that below one-third of the Debye temperature, effects of vibrations on the quantum mobility and diffusivity are both orders-of-magnitude larger and practically temperature independent. We have shown that both effects have their physical origin in the athermal lattice vibrations derived from the phonon ground state. The foregoing theory is tested in quantum molecular dynamics calculation of mobility and diffusivity of interstitial helium in bcc W. In this case, the Arrhenius law is only valid in a narrow range between ˜300 and ˜700 K. The diffusivity becomes temperature independent on the low-temperature side while increasing linearly with temperature on the high-temperature side.
Laurberg, Peter Thaysen; Weinreich, Ulla M Øller
2014-12-08
A 19-year-old woman with a history of juvenile laryngeal papillomatosis (JLP), treated since childhood with multiple resections, was admitted with symptoms of pneumonia. A chest X-ray and CAT-scan revealed multiple lung cysts and a bronchoalveolar lavage detected human papilloma virus 11. The patient responded well to antibiotics. A body plethysmography showed small lung volumes and low diffusion capacity for carbon monoxide, but normal volume diffusion capacity divided by alveolar volume. Pulmonary cystic disease should be considered when patients with JLP have symptoms of pneumonia.
Respiratory herpesvirus infection in two Indian Ringneck parakeets.
Lazic, Tatjana; Ackermann, Mark R; Drahos, Jo M; Stasko, Judith; Haynes, Joseph S
2008-03-01
A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was imported to the United States from Australia. Soon after, 1 parakeet suddenly died, and a second parakeet died after a 2-day course of illness, which consisted of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds had diffuse consolidation and red discoloration of the lungs, as well as thickened, congested air sacs. The microscopic examination revealed multifocal, necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of the affected airways contained numerous, large syncytial cells with up to 15 nuclei. The nuclei of these syncytial cells often contained large, eosinophilic inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and air sacs was hypertrophied and contained syncytial cells with intranuclear inclusion bodies similar to the bronchi. In addition, a few intranuclear inclusion bodies were also present in the epithelial cells that line the air capillaries. On ultrastructural examination, the nuclei of degenerating epithelial cells contained clusters of viral nucleocapsid proteins and unenveloped, icosahedral, viral particles that were approximately 90 nm in diameter. In addition, some epithelial cells contained clusters of enveloped viral particles approximately 105 nm in diameter, within the cytocavitary network. These lesions are characteristic of those caused by respiratory herpesvirus of parakeets.
Aggarwal, Rohit; McBurney, Christine; Schneider, Frank; Yousem, Samuel A; Gibson, Kevin F; Lindell, Kathleen; Fuhrman, Carl R; Oddis, Chester V
2017-03-01
To compare the survival outcomes between myositis-associated usual interstitial pneumonia (MA-UIP) and idiopathic pulmonary fibrosis (IPF-UIP). Adult MA-UIP and IPF-UIP patients were identified using CTD and IPF registries. The MA-UIP cohort included myositis or anti-synthetase syndrome patients with interstitial lung disease while manifesting UIP on high-resolution CT chest and/or a lung biopsy revealing UIP histology. IPF subjects met American Thoracic Society criteria and similarly had UIP histopathology. Kaplan-Meier survival curves compared cumulative and pulmonary event-free survival (event = transplant or death) between (i) all MA-UIP and IPF-UIP subjects, (ii) MA-UIP with biopsy proven UIP (n = 25) vs IPF-UIP subjects matched for age, gender and baseline forced vital capacity (±10%). Cox proportional hazards ratios compared the survival controlling for co-variates. Eighty-one IPF-UIP and 43 MA-UIP subjects were identified. The median cumulative and event-free survival time in IPF vs MA-UIP was 5.25/1.8 years vs 16.2/10.8 years, respectively. Cumulative and event-free survival was significantly worse in IPF-UIP vs MA-UIP [hazards ratio of IPF-UIP was 2.9 (95% CI: 1.5, 5.6) and 5.0 (95% CI: 2.8, 8.7) (P < 0.001), respectively]. IPF-UIP event-free survival (but not cumulative) remained significantly worse than MA-UIP with a hazards ratio of 6.4 (95% CI: 3.0, 13.8) after controlling for age at interstitial lung disease diagnosis, gender, ethnicity and baseline forced vital capacity%. Respiratory failure was the most common cause of death in both groups. A sub-analysis of 25 biopsy-proven MA-UIP subjects showed similar results. MA-UIP patients demonstrated a significant survival advantage over a matched IPF cohort, suggesting that despite similar histological and radiographic findings at presentation, the prognosis of MA-UIP is superior to that of IPF-UIP. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com
Lohmann, Katharina L.; Allen, Andrew L.
2015-01-01
A mature Quarter horse was euthanized following colic of 3 days duration. Postmortem, the large intestine, except the descending colon, was diffusely distended and associated with adhesion of the transverse colon to the pancreas, which had changes consistent with chronic active interstitial pancreatitis. Other lesions included hepatic fibrosis, erosive gastritis, and bilateral adrenal cortical hyperplasia. PMID:26538675
Kanchustambham, Venkat Kiran; Saladi, Swetha; Mahmoudassaf, Sarah; Patolia, Setu
2016-12-09
A woman aged 61 years presented to the emergency room with a 1-week history of dyspnoea on exertion and dry cough. X-ray of the chest showed diffuse interstitial opacities and was started on antibiotics and furosemide, and despite these measures, patient's respiratory status worsened, prompting endotracheal intubation. CT of the chest showed diffuse bilateral ground glass opacities and underwent bronchoscope with trans-bronchial biopsy that showed chronic bronchitis. Pt was empirically started on intravenous steroids due to concerns for interstitial lung disease (ILD). Autoimmune work up was sent and underwent video-assisted thoracoscopic surgery-guided biopsy of the lung that showed non-specific interstitial pattern with fibrosis. The patient was diagnosed as having antisynthetase syndrome with pulmonary involvement (ILD) as the cause of her acute respiratory failure. Azathioprine was started as steroid-sparing agent and was weaned off the ventilator to a tracheostomy collar and discharged to long-term rehabilitation centre. 2016 BMJ Publishing Group Ltd.
Application of thin-section low-dose chest CT (TSCT) in the management of pediatric AIDS.
Ambrosino, M M; Roche, K J; Genieser, N B; Kaul, A; Lawrence, R M
1995-01-01
The aim of this study was to evaluate the usefulness of thin-section low-dose computed tomography (TSCT) in the management of children with AIDS, as chest radiographs (CXR) often fail to adequately explain the patients' clinical status. We performed 54 noncontrast TSCTs on 32 children. The patients aged from 3 months to 14.6 years, were diagnosed as having bacterial pneumonia, lumphocytic interstitial pneumonitis (LIP), Pneumocystis carinii pneumonia (PCP), or Mycobacterium avium-intracellulare infection (MAI). The scans were correlated with the clinical diagnosis, T-lymphocyte-subset percentages, and p24-antigen levels. Subsegmental consolidations were seen in patients with LIP, PCP, and MAI, and as an isolated finding in those with only bacterial pneumonia. Ground-glass haziness was seen exclusively with acute PCP. Reticulonodular thickening was identified only in patients with LIP. Mosaic perfusion was seen with MAI, LIP, and pneumonia. The presence of adenopathy correlated with CD4+ T-cell subset percentages. The greatest value of CT in this study was in detecting new disease when chest films failed to correlate with a patient's clinical state, and in demonstrating acute/subacute disease in patients with severe baseline chest-film changes. Recurrent pneumonias may represent progression of "smoldering" disease, rather than true recurrent disease following complete clearing. Adenopathy with low CD4+ levels should suggest lymphoma or infection with MAI.
Evolution of Radiation Induced Defects in SiC: A Multiscale Simulation Approach
NASA Astrophysics Data System (ADS)
Jiang, Hao
Because of various excellent properties, SiC has been proposed for many applications in nuclear reactors including cladding layers in fuel rod, fission products container in TRISO fuel, and first wall/blanket in magnetic controlled fusion reactors. Upon exposure to high energy radiation environments, point defects and defect clusters are generated in materials in amounts significantly exceeding their equilibrium concentrations. The accumulation of defects can lead to undesired consequences such as crystalline-to-amorphous transformation1, swelling, and embrittlement, and these phenomena can adversely affect the lifetime of SiC based components in nuclear reactors. It is of great importance to understand the accumulation process of these defects in order to estimate change in properties of this material and to design components with superior ability to withstand radiation damages. Defect clusters are widely in SiC irradiated at the operation temperatures of various reactors. These clusters are believed to cause more than half of the overall swelling of irradiated SiC and can potentially lead to lowered thermal conductivity and mechanical strength. It is critical to understand the formation and growth of these clusters. Diffusion of these clusters is one importance piece to determine the growth rate of clusters; however it is unclear so far due to the challenges in simulating rare events. Using a combination of kinetic Activation Relaxation Technique with empirical potential and ab initio based climbing image nudged elastic band method, I performed an extensive search of the migration paths of the most stable carbon tri-interstitial cluster in SiC. This research reveals paths with the lowest energy barriers to migration, rotation, and dissociation of the most stable cluster. Based on these energy barriers, I concluded defect clusters are thermally immobile at temperatures lower than 1500 K and can dissociate into smaller clusters and single interstitials at temperatures beyond that. Even though clusters cannot diffuse by thermal vibrations, we found they can migrate at room temperature under the influence of electron radiation. This is the first direct observation of radiation-induced diffusion of defect clusters in bulk materials. We show that the underlying mechanism of this athermal diffusion is elastic collision between incoming electrons and cluster atoms. Our findings suggest that defect clusters may be mobile under certain irradiation conditions, changing current understanding of cluster annealing process in irradiated SiC. With the knowledge of cluster diffusion in SiC demonstrated in this thesis, we now become able to predict cluster evolution in SiC with good agreement with experimental measurements. This ability can enable us to estimate changes in many properties of irradiated SiC relevant for its applications in reactors. Internal interfaces such as grain boundaries can behave as sinks to radiation induced defects. The ability of GBs to absorb, transport, and annihilate radiation-induced defects (sink strength) is important to understand radiation response of polycrystalline materials and to better design interfaces for improved resistance to radiation damage. Nowadays, it is established GBs' sink strength is not a static property but rather evolves with many factors, including radiation environments, grain size, and GB microstructure. In this thesis, I investigated the response of small-angle tilt and twist GBs to point defects fluxes in SiC. First of all, I found the pipe diffusion of interstitials in tilt GBs is slower than bulk diffusion. This is because the increased interatomic distance at dislocation cores raises the migration barrier of interstitial dumbbells. Furthermore, I show that both the annihilation of interstitials at jogs and jog nucleation from clusters are diffusion-controlled and can occur under off-stoichiometric interstitial fluxes. Finally, a dislocation line model is developed to predict the role of tilt GBs in annihilating radiation damage. The model predicts the role of tilt GBs in annihilating defects depends on the rate of defects segregation to and diffusion along tilt GBs. Tilt GBs mainly serve as diffusion channel for defects to reach other sinks when defect diffusivity is high at boundaries. When defect diffusivity is low, most of the defects segregated to tilt GBs are annihilated by dislocation climb. Up-to-date, the response of twist GBs under irradiation has been rarely reported in literature and is still unclear. It is important to develop atom scale insight on this question in order to predict twist GBs' sink strength for a better understanding of radiation response of polycrystalline materials. By using a combination of molecular dynamics and grand canonical Monte Carlo, here I demonstrate the defect kinetics in {001} and {111} twist GBs and the microstructural evolution of these GBs under defect fluxes in SiC. I found due to the deep potential well for interstitials at dislocation intersections within the interface, the mobility of defects on dislocation grid is retard and this leads to defect accumulation at GBs for many cases. Furthermore, I conclude both types of twist GBs have to form mixed dislocations with edge component in order to absorb accumulated interstitials at the interface. The formation of mixed dislocation is either by interstitial loop nucleation or by dislocation reactions at the interface. The continuous formation and climb of these mixed dislocations make twist GBs unsaturatable sinks to radiation induced defects.
Damage to the Silicon Substrate by Reactive Ion Etching Detected by a Slow Positron Beam
NASA Astrophysics Data System (ADS)
Wei, Long; Tabuki, Yasushi; Tanigawa, Shoichiro
1993-01-01
Defects in reactive ion-etched Si have been investigated by means of a slow positron beam. A thin carbon-containing film (<30 Å) was formed on the Si surface after reactive ion etching (RIE). Vacancy-type defects, which were estimated to distribute over 1200 Å in depth by numerical fitting using the positron trapping model, were observed in the damaged subsurface region of Si. Aside from ion bombardment, ultraviolet radiation is also presumed to affect the formation of vacancies, interstitials in oxide and the formation of vacancies in Si substrate. The ionization-enhanced diffusion (IED) mechanism is expected to promote the diffusion of vacancies and interstitials into Si substrate.
Bacterial infection and acute lung injury in hamsters.
Seidenfeld, J J; Mullins, R C; Fowler, S R; Johanson, W G
1986-07-01
Bacterial pneumonia is a common complication of lung injury that can be an important determinant of outcome. We studied experimental lung injury produced in hamsters by injecting 20 mg/kg paraquat (PQ) intraperitoneally; control animals received saline vehicle. Three days later, Pseudomonas aeruginosa (PAO1), 10(8) organisms in 0.25 ml, or saline, 0.25 ml, was inoculated intratracheally. Lung and systemic antibacterial defenses were studied at death 24 h later. Paraquat alone produced focal interstitial pneumonitis and neutrophilic alveolitis, and resulted in a 12% (3 of 26) mortality. PAO1 alone caused focal pneumonias and no deaths. Animals receiving both agents (PAO1/PQ) had extensive diffuse alveolar damage characterized by alveolar hemorrhage, edema, influx of neutrophils, and vasculitis; 50% (16 of 32) died within 96 h of PQ injection. Mean lung counts of PAO1 at death were 7.6 X 10(4) colony forming units/g in PAO1 and 2.8 X 10(7) in PAO1/PQ animals (p less than 0.05). PAO1 colony counts in liver were increased nearly 100-fold in PAO1/PQ animals (p less than 0.05). Half-time of clearance of P. aeruginosa from the blood was prolonged in PAO1 and in PAO1/PQ animals (p less than 0.05) but not in PQ animals. Phagocytosis of Staphylococcus aureus by leukocytes lavaged from the lung was not impaired in any group compared with that in control animals, but intracellular killing was impaired in PAO1 and PAO1/PQ but not in PQ animals. Paraquat injury impairs lung antibacterial defenses by uncertain mechanisms. Superinfection of PQ-injured lungs by PAO1 appears responsible for defects in intrapulmonary and systemic antibacterial defenses.
Chéhère, Baptiste; Bougault, Valérie; Chenivesse, Cécile; Grosbois, Jean-Marie; Wallaert, Benoit
2018-06-14
Pulmonary rehabilitation (PR) improves performance in the 6-min walk test (6MWT) in a subset of patients with fibrotic idiopathic interstitial pneumonia (f-IIP); however, a large proportion of patients do not respond to PR. To investigate the effects of a PR program on cardiorespiratory responses during a 6MWT and to identify the characteristics of patients who do not show improved performance after PR. An observational study. Patients were recruited from the Competence Centre for Rare Pulmonary Diseases at Lille University Hospital, France and completed an 8-week home-based PR program. A total of 19 patients with f-IIP; 12 with idiopathic pulmonary fibrosis (IPF) and 7 with fibrotic non-specific interstitial pneumonia. Patients underwent spirometry and completed a 6MWT before and after an 8- week PR program. Gas exchange, heart rate, and pulse O2 saturation were measured continuously during the 6MWT. Quality of life, dyspnoea, and anxiety/depression were assessed using the Short-Form 36 (SF-36), the baseline/transition dyspnoea index (BDI/TDI), and the Hospital Anxiety and Depression Scale (HADS) questionnaires. Patients who did and did not improve the distance walked in the 6MWT by at least 30 m after PR were classified as responders (n=9) and non-responders (n=10), respectively. O2 uptake, ventilation rate, and distance covered during the 6MWT were significantly improved only in the responder group (p<0.05). Changes in SF-36, BDI/TDI, and HADS scores did not differ significantly between responders and non-responders. The non-responder group contained significantly more patients with IPF (p<0.05) and experienced greater arterial oxygen desaturation during the 6MWT compared with the responder group. Failure to improve performance in the 6MWT after PR was associated with a diagnosis of IPF, non-improvement in gas exchange, and greater arterial oxygen desaturation. Most f-IIP patients who did not respond to PR were diagnosed with IPF and displayed greater hypoxemia during exercise. Clinical practitioners should seek to determine why patients fail to improve exercise performance after PR and propose an alternative exercise regimen to these patients.
Crystal defect studies using x-ray diffuse scattering
DOE Office of Scientific and Technical Information (OSTI.GOV)
Larson, B.C.
1980-01-01
Microscopic lattice defects such as point (single atom) defects, dislocation loops, and solute precipitates are characterized by local electronic density changes at the defect sites and by distortions of the lattice structure surrounding the defects. The effect of these interruptions of the crystal lattice on the scattering of x-rays is considered in this paper, and examples are presented of the use of the diffuse scattering to study the defects. X-ray studies of self-interstitials in electron irradiated aluminum and copper are discussed in terms of the identification of the interstitial configuration. Methods for detecting the onset of point defect aggregation intomore » dislocation loops are considered and new techniques for the determination of separate size distributions for vacancy loops and interstitial loops are presented. Direct comparisons of dislocation loop measurements by x-rays with existing electron microscopy studies of dislocation loops indicate agreement for larger size loops, but x-ray measurements report higher concentrations in the smaller loop range. Methods for distinguishing between loops and three-dimensional precipitates are discussed and possibilities for detailed studies considered. A comparison of dislocation loop size distributions obtained from integral diffuse scattering measurements with those from TEM show a discrepancy in the smaller sizes similar to that described above.« less
LEE, Seung-Hun; PARK, Sang-Joon; KWAK, Dongmi; KIM, Kyoo-Tae
2017-01-01
A 16-year-old female Indian peafowl (Pavo cristatus) died two days after recognition of conjunctivitis in the right eye, anorexia and depression. Gross necropsy revealed a thick pseudomembrane under the eyelid and hydropericardium. Histopathological examination revealed hepatocellular necrosis, sinusoidal and vascular congestion and infiltrated inflammatory cells. Infiltration by inflammatory cells was noted in the epicardium. The lungs had mild interstitial pneumonia with the extensive congestion within the capillaries of the air sacs. Tubular interstitial congestion and necrosis was noted in the kidneys. Bacterial culture and nucleotide sequencing of the inflammatory specimens identified the causative agent as Serratia marcescens, an uncommon bacterium in birds. In summary, this study describes the sudden death of an Indian peafowl due to S. marcescens infection, which is rarely seen in animals. PMID:29081475
Cunha, Burke A; Syed, Uzma; Mickail, Nardeen
2011-01-01
We present a young woman with a negative medical history who presented with acute systemic lupus erythematosus (SLE) pneumonitis mimicking swine influenza (H1N1) pneumonia. Because this case occurred during the H1N1 pandemic, the initial diagnostic impression was of H1N1 pneumonia. Although her clinical and laboratory findings were consistent with the diagnosis of H1N1 pneumonia, e.g., fever, sore throat, dry cough, arthralgias, myalgias, thrombocytopenia, relative lymphopenia, and elevated serum transaminases, some findings suggested an alternate diagnosis, e.g., leukopenia, a highly elevated erythrocyte sedimentation rate, highly elevated serum ferritin levels, elevated antinuclear antibody (ANA) levels, and double-stranded (DS) DNA titers. Her chest x-ray showed an accentuation of basilar lung markings, with a small pleural effusion similar to the chest x-ray findings of early H1N1 pneumonia. Initially, her headaches were thought to be related to central nervous system manifestations of H1N1. After laboratory test results demonstrated elevated ANA and anti-DS DNA titers, she was diagnosed with acute SLE pneumonitis. The take-home lesson for clinicians is that other infectious diseases, e.g., human parainfluenza virus or Legionnaires' disease, can mimic H1N1 pneumonia during an influenza pandemic. Excluding asthma, congestive heart failure, exacerbations of acute bronchitis, chronic obstructive pulmonary disorder, and pulmonary interstitial disease, noninfectious mimics of H1N1 are extremely rare. To the best of our knowledge, this is the first reported case of de novo SLE pneumonitis mimicking H1N1 pneumonia during the swine influenza pandemic. Copyright © 2011 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Roehl, Jason L.
Diffusion of point defects on crystalline surfaces and in their bulk is an important and ubiquitous phenomenon affecting film quality, electronic properties and device functionality. A complete understanding of these diffusion processes enables one to predict and then control those processes. Such understanding includes knowledge of the structural, energetic and electronic properties of these native and non-native point defect diffusion processes. Direct experimental observation of the phenomenon is difficult and microscopic theories of diffusion mechanisms and pathways abound. Thus, knowing the nature of diffusion processes, of specific point defects in given materials, has been a challenging task for analytical theory as well as experiment. The recent advances in computing technology have been a catalyst for the rise of a third mode of investigation. The advent of tremendous computing power, breakthroughs in algorithmic development in computational applications of electronic density functional theory now enables direct computation of the diffusion process. This thesis demonstrates such a method applied to several different examples of point defect diffusion on the (001) surface of gallium arsenide (GaAs) and the bulk of cadmium telluride (CdTe) and cadmium sulfide (CdS). All results presented in this work are ab initio, total-energy pseudopotential calculations within the local density approximation to density-functional theory. Single particle wavefunctions were expanded in a plane-wave basis and reciprocal space k-point sampling was achieved by Monkhorst-Pack generated k-point grids. Both surface and bulk computations employed a supercell approach using periodic boundary conditions. Ga adatom adsorption and diffusion processes were studied on two reconstructions of the GaAs(001) surface including the c(4x4) and c(4x4)-heterodimer surface reconstructions. On the GaAs(001)- c(4x4) surface reconstruction, two distinct sets of minima and transition sites were discovered for a Ga adatom relaxing from heights of 3 and 0.5 A from the surface. These two sets show significant differences in the interaction of the Ga adatom with surface As dimers and an electronic signature of the differences in this interaction was identified. The energetic barriers to diffusion were computed between various adsorption sites. Diffusion profiles for native Cd and S, adatom and vacancy, and non-native interstitial adatoms of Te, Cu and Cl were investigated in bulk wurtzite CdS. The interstitial diffusion paths considered in this work were chosen parallel to c-axis as it represents the path encountered by defects diffusing from the CdTe layer. Because of the lattice mismatch between zinc-blende CdTe and hexagonal wurtzite CdS, the c-axis in CdS is normal to the CdTe interface. The global minimum and maximum energy positions in the bulk unit cell vary for different diffusing species. This results in a significant variation, in the bonding configurations and associated strain energies of different extrema positions along the diffusion paths for various defects. The diffusion barriers range from a low of 0.42 eV for an S interstitial to a high of 2.18 eV for a S vacancy. The computed 0.66 eV barrier for a Cu interstitial is in good agreement with experimental values in the range of 0.58 - 0.96 eV reported in the literature. There exists an electronic signature in the local density of states for the s- and d-states of the Cu interstitial at the global maximum and global minimum energy position. The work presented in this thesis is an investigation into diffusion processes for semiconductor bulk and surfaces. The work provides information about these processes at a level of control unavailable experimentally giving an elaborate description into physical and electronic properties associated with diffusion at its most basic level. Not only does this work provide information about GaAs, CdTe and CdS, it is intended to contribute to a foundation of knowledge that can be extended to other systems to expand our overall understanding into the diffusion process. (Abstract shortened by UMI.)
Effects of applied strain on nanoscale self-interstitial cluster formation in BCC iron
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gao, Ning; Setyawan, Wahyu; Kurtz, Richard J.
2017-09-01
The effect of applied strains on the configurational evolution of self-interstitial clusters in BCC iron (Fe) is explored with atomistic simulations. A novel cluster configuration is discovered at low temperatures (<600 K), which consists of <110> dumbbells and <111> crowdions in a specific configuration, resulting in an immobile defect. The stability and diffusion of this cluster at higher temperatures is explored. In addition, an anisotropy distribution factor of a particular [hkl] interstitial loop within the family of loops is calculated as a function of strain. The results show that loop anisotropy is governed by the angle between the stress directionmore » and the orientation of the <111> crowdions in the loop, and directly linked to the stress induced preferred nucleation of self-interstitial atoms.« less
Interstitial Fluid Flow and Drug Delivery in Vascularized Tumors: A Computational Model
Welter, Michael; Rieger, Heiko
2013-01-01
Interstitial fluid is a solution that bathes and surrounds the human cells and provides them with nutrients and a way of waste removal. It is generally believed that elevated tumor interstitial fluid pressure (IFP) is partly responsible for the poor penetration and distribution of therapeutic agents in solid tumors, but the complex interplay of extravasation, permeabilities, vascular heterogeneities and diffusive and convective drug transport remains poorly understood. Here we consider–with the help of a theoretical model–the tumor IFP, interstitial fluid flow (IFF) and its impact upon drug delivery within tumor depending on biophysical determinants such as vessel network morphology, permeabilities and diffusive vs. convective transport. We developed a vascular tumor growth model, including vessel co-option, regression, and angiogenesis, that we extend here by the interstitium (represented by a porous medium obeying Darcy's law) and sources (vessels) and sinks (lymphatics) for IFF. With it we compute the spatial variation of the IFP and IFF and determine its correlation with the vascular network morphology and physiological parameters like vessel wall permeability, tissue conductivity, distribution of lymphatics etc. We find that an increased vascular wall conductivity together with a reduction of lymph function leads to increased tumor IFP, but also that the latter does not necessarily imply a decreased extravasation rate: Generally the IF flow rate is positively correlated with the various conductivities in the system. The IFF field is then used to determine the drug distribution after an injection via a convection diffusion reaction equation for intra- and extracellular concentrations with parameters guided by experimental data for the drug Doxorubicin. We observe that the interplay of convective and diffusive drug transport can lead to quite unexpected effects in the presence of a heterogeneous, compartmentalized vasculature. Finally we discuss various strategies to increase drug exposure time of tumor cells. PMID:23940570
McAllister, Tim A.; Ayroud, Mejid; Bray, Tammy M.; Yost, Garold S.
2006-01-01
Abstract Over a 3-y period, 906 000 cattle were monitored in 23 feedlots in southern Alberta for symptoms of acute interstitial pneumonia (AIP). Plasma, urine, and lung tissue were collected at slaughter from 299 animals clinically diagnosed with AIP and from 156 healthy penmates and analyzed for 3-methylindole (3MI) derivatives and reduced glutathione concentration. From each animal, the left lung was subsampled for histologic examination. Concentrations of glutathione in lung tissue were reduced (P < 0.001) in animals showing clinical symptoms of AIP as compared with their asymptomatic penmates. Animals histologically confirmed as having AIP had higher levels of 3MI protein adducts in blood and lung tissue (P < 0.05) than did emergency-slaughtered animals without AIP. Within feedlots, where pens of heifers were fed either a standard dosage of melengestrol acetate (MGA) or none, the rate of death attributable to AIP was similar between treatment groups, but emergency slaughter after clinical diagnosis of AIP was done 3.2 times more often (P < 0.001) in the MGA-fed heifers than in the group not fed MGA. Use of MGA did not influence glutathione concentration. As growth performance of heifers given steroidal implants may not be improved by feeding MGA, the most cost-effective method of reducing the incidence of AIP-related emergency slaughter in feedlot heifers may be to eliminate MGA from the diet. PMID:16850945
Miyamoto, Atsushi; Kurosaki, Atsuko; Fujii, Takeshi; Kishi, Kazuma; Homma, Sakae
2017-05-01
Lung cancer is prevalent among patients with interstitial pneumonia (IP). HRCT findings mucinous adenocarcinoma in patients with IP have not been described. In 112 consecutive patients with 120 surgically resected IP-associated lung cancers, 42 patients had pathologically proven invasive adenocarcinoma (IA). A total of 14 out of 42 patients (10 men, 4 women, mean age, 68.4 years) had invasive mucinous adenocarcinoma. We reviewed the patients' medical records and HRCT scans. Invasive mucinous adenocarcinoma were most commonly associated with idiopathic IP (n = 13) affecting the lower lobe adjacent to a fibrocystic changes. In 11 patients with invasive mucinous adenocarcinoma or other types of IA, the tumour was adjacent to a fibrocystic lesion. In invasive mucinous adenocarcinoma, malignant signs included lobulation (n = 11), spiculation (n = 9), vascular convergence (n = 10) and pleural indentation (n = 2). Characteristic findings of mucinous adenocarcinoma (i.e. vague margins (n = 10), lobular-bounded margins (n = 11), air bronchogram (n = 11) and bubble-like low attenuation (n = 8)) were more common in invasive mucinous adenocarcinoma than in other IA types. All invasive mucinous adenocarcinoma tumours (n = 11) were closely associated with fibrosis. Mixed ground-glass opacity and consolidation adjacent to a fibrocystic lesion with malignant signs and characteristic features of mucinous adenocarcinoma indicate malignancy. © 2016 Asian Pacific Society of Respirology.
A novel cause of community-acquired pneumonia in a young immunocompetent host.
James, Nicholas; Gilman, Matthew; Duncan, Robert; Gray, Anthony
2016-09-01
Diffuse pulmonary infiltrates represent a common problem encountered by pulmonologists. The differential diagnosis is extensive and includes infectious, inflammatory, environmental and malignant conditions. Appropriate evaluation, aside from a thorough history and physical examination, includes serologic, radiographic and procedural elements. We describe a case of a healthy male with diffuse pulmonary infiltrates. Work up revealed a novel infectious etiology. Although this particular microorganism has been described to cause native valve endocarditis, recurrent breast abscesses, osteomyelitis and bacteremia, it has to date not been described as a cause for community acquired pneumonia in immunocompetent hosts. © 2014 John Wiley & Sons Ltd.
Mizuno, Ryuichi; Asano, Koichiro; Mikami, Shuji; Nagata, Hirohiko; Kaneko, Gou; Oya, Mototsugu
2012-05-01
To elucidate the patterns of interstitial lung disease during everolimus treatment in patients with metastatic renal cell carcinoma, we reviewed seven cases of everolimus-induced interstitial lung disease. Seven patients with metastatic renal cell carcinoma, which continued to progress despite treatment with sunitinib or sorafenib, developed interstitial lung disease after treatment with everolimus. Chest X-ray demonstrated diffuse infiltrates in lung fields, and chest computed tomography showed bilateral reticular and ground-glass opacities. Serum levels of lactate dehydrogenase (7/7), C-reactive protein (6/7), pulmonary surfactant associated protein D (1/7) and Krebs von den Lungen 6 (5/7) were elevated. The bronchoalveolar lavage fluid obtained from four patients with Grade 3 interstitial lung disease showed lymphocytosis. The transbronchial lung biopsy specimens showed interstitial lymphocytic infiltration and septal thickening of alveolar walls. In two cases with mild interstitial lung disease, the everolimus therapy was successfully continued. In four cases with Grade 3 interstitial lung disease, the drug was discontinued and steroid therapy was initiated. Pulmonary symptoms and radiological abnormalities resolved within 2 months. Serum Krebs von den Lungen 6 was elevated compared with baseline in all cases with interstitial lung disease. Some patients who developed mild interstitial lung disease during everolimus treatment could continue to receive the treatment. Even when severe interstitial lung disease developed, withdrawal of the drug and short-term use of high-dose steroids resulted in rapid recovery. Prompt recognition of interstitial lung disease exacerbation as well as exclusion of progressive disease or infection is of primary importance.
Use of cylindrical diffusing fibers as detectors for interstitial tissue spectroscopy
NASA Astrophysics Data System (ADS)
Baran, Timothy M.; Foster, Thomas H.
2015-03-01
Interstitial photodynamic therapy (iPDT) describes the use of implanted optical fibers for delivery of treatment light to activate photosensitizer in regions that can be located deep within the body. Since sensitive healthy structures are often located nearby, this requires careful treatment planning that is dependent on tissue optical properties. Determination of these values usually involves the insertion of additional fibers into the volume, or the use of flat-cleaved optical fibers as both treatment sources and detectors. The insertion of additional fibers is undesirable, and cylindrical diffusers have been shown to offer superior treatment characteristics compared to flat-cleaved fibers. Using cylindrical diffusers as detectors for spectroscopic measurement is therefore attractive. We describe the determination of the detection profile for a particular cylindrical diffuser design and derive the scatterer concentration gradient within the diffuser core. This detection profile is compared to previously characterized diffusers, and is shown to be dependent on the diffuser design. For diffusers with a constant scatterer concentration and distal mirror, the detection profile is localized to the proximal end of the diffusing region. For diffusers with variable scattering concentration along their length and no distal mirror, the detection profile is shown to be more uniform along the diffusing region. We also present preliminary results showing the recovery of optical properties using arrays of cylindrical diffusing fibers as sources and detectors, with a mean error of 4.4% in the determination of μeff. The accuracy of these results is comparable to those obtained with other methods of optical property recovery.
Inferring diameters of spheres and cylinders using interstitial water.
Herrera, Sheryl L; Mercredi, Morgan E; Buist, Richard; Martin, Melanie
2018-06-04
Most early methods to infer axon diameter distributions using magnetic resonance imaging (MRI) used single diffusion encoding sequences such as pulsed gradient spin echo (SE) and are thus sensitive to axons of diameters > 5 μm. We previously simulated oscillating gradient (OG) SE sequences for diffusion spectroscopy to study smaller axons including the majority constituting cortical connections. That study suggested the model of constant extra-axonal diffusion breaks down at OG accessible frequencies. In this study we present data from phantoms to test a time-varying interstitial apparent diffusion coefficient. Diffusion spectra were measured in four samples from water packed around beads of diameters 3, 6 and 10 μm; and 151 μm diameter tubes. Surface-to-volume ratios, and diameters were inferred. The bead pore radii estimates were 0.60±0.08 μm, 0.54±0.06 μm and 1.0±0.1 μm corresponding to bead diameters ranging from 2.9±0.4 μm to 5.3±0.7 μm, 2.6±0.3 μm to 4.8±0.6 μm, and 4.9±0.7 μm to 9±1 μm. The tube surface-to-volume ratio estimate was 0.06±0.02 μm -1 corresponding to a tube diameter of 180±70 μm. Interstitial models with OG inferred 3-10 μm bead diameters from 0.54±0.06 μm to 1.0±0.1 μm pore radii and 151 μm tube diameters from 0.06±0.02 μm -1 surface-to-volume ratios.
Mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor in a ferret
INOUE, Saki; YONEMARU, Kayoko; YANAI, Tokuma; SAKAI, Hiroki
2014-01-01
A 5-year-old male ferret presented with an enlarged canalicular testis in the left inguinal region. Microscopically, the enlarged testis consisted of a diffuse intimately admixed proliferation of c-kit-positive germ cell-like and Wilms tumor-1 protein-positive Sertoli cell-like components, but no Call-Exner body was detected. In addition, the compact proliferation of steroidogenic acute regulatory protein-intense positive interstitial cells was identified in a separate peripheral area of the mass. Based on histopathological and immunohistochemical findings, the tumor was diagnosed as a mixed germ cell-sex cord-stromal tumor with a concurrent interstitial cell tumor. PMID:25311985
NASA Astrophysics Data System (ADS)
Zhang, X.; Connelly, D.; Takeuchi, H.; Hytha, M.; Mears, R. J.; Rubin, L. M.; Liu, T.-J. K.
2018-03-01
The effects of oxygen-inserted (OI) layers on the diffusion of boron (B), phosphorus (P), and arsenic (As) in silicon (Si) are investigated, for ultra-shallow junction formation by high-dose ion implantation followed by rapid thermal annealing. The projected range (Rp) of the implanted dopants is shallower than the depth of the OI layers. Secondary ion mass spectrometry is used to compare the dopant profiles in silicon samples that have OI layers against the dopant profiles in control samples that do not have OI layers. Diffusion is found to be substantially retarded by the OI layers for B and P, and less for As, providing shallower junction depth. The experimental results suggest that the OI layers serve to block the diffusion of Si self-interstitials and thereby effectively reduce interstitial-aided diffusion beyond the depth of the OI layers. The OI layers also help to retain more dopants within the Si, which technology computer-aided design simulations indicate to be beneficial for achieving shallower junctions with lower sheet resistance to enable further miniaturization of planar metal-oxide-semiconductor field-effect transistors for improved integrated-circuit performance and cost per function.
NASA Astrophysics Data System (ADS)
Lampin, E.; Cristiano, F.; Lamrani, Y.; Colombeau, B.
2004-02-01
We present simulations of B TED based on a complete calculation of the extended defect growth/shrinkage during annealing. The Si self-interstitial supersaturation calculated at the extended defect depth is coupled to the set of equations for the B kick-out diffusion through a generation/recombination term in the diffusion equation of the Si self-interstitials. The simulations are compared to the measurements performed on a Si wafer containing several B marker layers, where the amount of TED varies from one peak to the other. The good agreement obtained on this experiment is very promising for the application of these calculations to the case of ultra-shallow B + implants.
2013-01-01
Dogs are companion animals that live in close proximity with humans. Canine H3N2 influenza virus has been isolated from pet dogs that showed severe respiratory signs and other clinical symptoms such as fever, reduced body weight, and interstitial pneumonia. The canine H3N2 influenza virus can be highly transmissible among dogs via aerosols. When we analyzed global gene expression in the lungs of infected dogs, the genes associated with the immune response and cell death were greatly elevated. Taken together, our results suggest that canine H3N2 influenza virus can be easily transmitted among dogs, and that severe pneumonia in the infected dogs may be partially due to the elevated expression of genes related to inflammation and apoptosis. PMID:24090140
Bedenić, B; Boras, A
2001-01-01
The plasmid-mediated extended-spectrum beta-lactamases (ESBL) confer resistance to oxymino-cephalosporins, such as cefotaxime, ceftazidime, and ceftriaxone and to monobactams such as aztreonam. It is well known fact that ESBL producing bacteria exhibit a pronounced inoculum effect against broad spectrum cephalosporins like ceftazidime, cefotaxime, ceftriaxone and cefoperazone. The aim of this investigation was to determine the effect of inoculum size on the sensitivity and specificity of double-disk synergy test (DDST) which is the test most frequently used for detection of ESBLs, in comparison with other two methods (determination of ceftazidime MIC with and without clavulanate and inhibitor potentiated disk-diffusion test) which are seldom used in clinical laboratories. The experiments were performed on a set of K. pneumoniae strains with previously characterized beta-lactamases which comprise: 10 SHV-5 beta-lactamase producing K. pneumoniae, 20 SHV-2 + 1 SHV 2a beta-lactamase producing K. pneumoniae, 7 SHV-12 beta-lactamase producing K. pneumoniae, 39 putative SHV ESBL producing K. pneumoniae and 26 K. pneumoniae isolates highly susceptible to ceftazidime according to Kirby-Bauer disk-diffusion method and thus considered to be ESBL negative. According to the results of this investigation, increase in inoculum size affected more significantly the sensitivity of DDST than of other two methods. The sensitivity of the DDST was lower when a higher inoculum size of 10(8) CFU/ml was applied, in distinction from other two methods (MIC determination and inhibitor potentiated disk-diffusion test) which retained high sensitivity regardless of the density of bacterial suspension. On the other hand, DDST displayed higher specificity compared to other two methods regardless of the inoculum size. This investigation found that DDST is a reliable method but it is important to standardize the inoculum size.
NASA Astrophysics Data System (ADS)
Volkov, Vladimir V.; Loshchenov, V. B.; Konov, Vitalii I.; Kononenko, Vitalii V.
2010-10-01
We report techniques for the fabrication of laser radiation diffusers for interstitial photodynamic therapy. Using chemical etching of the distal end of silica fibre with a core diameter of 200 — 600 μm, we have obtained long (up to 40 mm) diffusers with good scattering uniformity. Laser ablation has been used to produce cylindrical diffusers with high emission contrast and a scattering uniformity no worse than ~10 % in their middle part. The maximum length of the diffusers produced by this method is 20 — 25 mm.
Olsen, Raina J.; Jin, Ke; Lu, Chenyang; ...
2015-11-23
The nature of defect clusters in Ni and Nimore » $$_{50}$$Co$$_{50}$$ (NiCo) irradiated at room temperature with 2–16 MeV Ni ions is studied using asymptotic diffuse X-ray scattering and transmission electron microscopy (TEM). Analysis of the scattering data provides separate size distributions for vacancy and interstitial type defect clusters, showing that both types of defect clusters have a smaller size and higher density in NiCo than in Ni. Diffuse scattering results show good quantitative agreement with TEM results for cluster sizes greater than 4 nm diameter, but find that the majority of vacancy clusters are under 2 nm in NiCo, which, if not detected, would lead to the conclusion that defect density was actually lower in the alloy. Interstitial dislocation loops and stacking fault tetrahedra are identified by TEM. Lastly comparison of diffuse scattering lineshapes to those calculated for dislocation loops and SFTs indicates that most of the vacancy clusters are SFTs.« less
Murray, Gerard M; More, Simon J; Sammin, Dónal; Casey, Mìcheàl J; McElroy, Máire C; O'Neill, Rónan G; Byrne, William J; Earley, Bernadette; Clegg, Tracy A; Ball, Hywel; Bell, Colin J; Cassidy, Joseph P
2017-01-01
We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.
Effects of applied strain on nanoscale self-interstitial cluster formation in BCC iron
NASA Astrophysics Data System (ADS)
Gao, Ning; Setyawan, Wahyu; Kurtz, Richard J.; Wang, Zhiguang
2017-09-01
The effect of applied strains on the configurational evolution of self-interstitial clusters in BCC iron (Fe) is explored with atomistic simulations. A novel cluster configuration is discovered at low temperatures (<600 K), which consists of 〈 110 〉 dumbbells and 〈 111 〉 crowdions in a specific configuration, resulting in an immobile defect. The stability and diffusion of this cluster at higher temperatures is explored. In addition, an anisotropy distribution factor of a particular [ hkl ] interstitial loop within the family of 〈 hkl 〉 loops is calculated as a function of strain. The results show that loop anisotropy is governed by the angle between the stress direction and the orientation of the 〈 111 〉 crowdions in the loop, and directly linked to the stress induced preferred nucleation of self-interstitial atoms.
Miller, Albert; Warshaw, Raphael; Nezamis, James
2013-12-01
Asbestosis is an interstitial lung disease whose radiographic severity has long been graded by the International Labour Office (ILO) profusion score. Its effect on pulmonary function is further impacted by asbestos related pleural thickening. This report aims to describe the relationships between radiographic grading of interstitial and pleural fibrosis and a key test of pulmonary function, the diffusing capacity, which measures gas exchange and has rarely been assessed in large groups, and to confirm the relationship to an independent test of pulmonary function, the vital capacity, which measures a mechanical property of the lungs. The data were derived from a survey during the period 1997-2004 of 5,003 workers (all white males) exposed to asbestos in various trades. Tests included chest radiographs read by a certified expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLco). Cigarette smoking was adjusted for in the predictive equation for DLCO . Workers were evaluated at a mobile facility at work sites in four southern states. Both diffusing capacity and vital capacity were negatively correlated with profusion score over the full spectrum of radiographic severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0 (conventionally classified as abnormal) were associated with similar diffusing capacity and vital capacity values. The highest profusion scores were associated with a greater proportionate decrease in diffusing capacity than in FVC. Both tests showed an effect of pleural fibrosis. Both radiographic severity graded by the profusion score and pleural thickening are correlated with two independent measures of pulmonary function. FVC (which had been reported in smaller work forces) and DLCO (which has not been reported). Both measures show a decrease from normal to intermediate (0/1, 1/0) scores and a further decrease with greater scores, demonstrating the consistency of radiographic and functional assessments. © 2013 Wiley Periodicals, Inc.
Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret
Carpenter, J.W.; Davidson, J.P.; Novilla, M.N.; Huang, J.C.M.
1980-01-01
A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.
Metastatic, papillary cystadenocarcinoma of the mammary gland in a black-footed ferret.
Carpenter, J W; Davidson, J P; Novilla, M N; Huang, J C
1980-10-01
A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.
[New toxicity of fotemustine: diffuse interstitial lung disease].
Bertrand, M; Wémeau-Stervinou, L; Gauthier, S; Auffret, M; Mortier, L
2012-04-01
Fotemustine is an alkylating cytostatic drug belonging to the nitrosourea family and is used in particular in the treatment of disseminated malignant melanoma. Herein, we report a case of interstitial lung disease associated with fotemustine. An 81-year-old man treated with fotemustine for metastatic melanoma presented acute interstitial lung disease 20 days after a fourth course of fotemustine monotherapy. The condition regressed spontaneously, with the patient returning to the clinical, radiological and blood gas status that had preceded fotemustine treatment. After other potential aetiologies had been ruled out, acute fotemustine-induced lung toxicity was considered and this treatment was definitively withdrawn. Other cytostatic agents belonging to the nitrosourea family can cause similar pictures, with a number of cases of interstitial lung disease thus being ascribed to fotemustine and dacarbazine. To our knowledge, this is the first case of interstitial lung disease induced by fotemustine monotherapy. This diagnosis should be considered where respiratory signs appear in melanoma patients undergoing fotemustine treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Günther, A; Mosavi, P; Heinemann, S; Ruppert, C; Muth, H; Markart, P; Grimminger, F; Walmrath, D; Temmesfeld-Wollbrück, B; Seeger, W
2000-02-01
Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.
Idiopathic Interstitial Pneumonia
Flaherty, Kevin R.; Andrei, Adin-Cristian; King, Talmadge E.; Raghu, Ganesh; Colby, Thomas V.; Wells, Athol; Bassily, Nadir; Brown, Kevin; du Bois, Roland; Flint, Andrew; Gay, Steven E.; Gross, Barry H.; Kazerooni, Ella A.; Knapp, Robert; Louvar, Edmund; Lynch, David; Nicholson, Andrew G.; Quick, John; Thannickal, Victor J.; Travis, William D.; Vyskocil, James; Wadenstorer, Frazer A.; Wilt, Jeffrey; Toews, Galen B.; Murray, Susan; Martinez, Fernando J.
2007-01-01
Rationale: Treatment and prognoses of diffuse parenchymal lung diseases (DPLDs) varies by diagnosis. Obtaining a uniform diagnosis among observers is difficult. Objectives: Evaluate diagnostic agreement between academic and community-based physicians for patients with DPLDs, and determine if an interactive approach between clinicians, radiologists, and pathologists improved diagnostic agreement in community and academic centers. Methods: Retrospective review of 39 patients with DPLD. A total of 19 participants reviewed cases at 2 community locations and 1 academic location. Information from the history, physical examination, pulmonary function testing, high-resolution computed tomography, and surgical lung biopsy was collected. Data were presented in the same sequential fashion to three groups of physicians on separate days. Measurements and Main Results: Each observer's diagnosis was coded into one of eight categories. A κ statistic allowing for multiple raters was used to assess agreement in diagnosis. Interactions between clinicians, radiologists, and pathologists improved interobserver agreement at both community and academic sites; however, final agreement was better within academic centers (κ = 0.55–0.71) than within community centers (κ = 0.32–0.44). Clinically significant disagreement was present between academic and community-based physicians (κ = 0.11–0.56). Community physicians were more likely to assign a final diagnosis of idiopathic pulmonary fibrosis compared with academic physicians. Conclusions: Significant disagreement exists in the diagnosis of DPLD between physicians based in communities compared with those in academic centers. Wherever possible, patients should be referred to centers with expertise in diffuse parenchymal lung disorders to help clarify the diagnosis and provide suggestions regarding treatment options. PMID:17255566
Kellihan, Heidi B; Waller, Kenneth R; Pinkos, Alyssa; Steinberg, Howard; Bates, Melissa L
2015-09-01
To describe clinical canine patients with naturally occurring pulmonary hypertension and radiographic pulmonary alveolar infiltrates before and after treatment with sildenafil. Ten client-owned dogs. A retrospective analysis of dogs with echocardiographically-determined pulmonary hypertension and pulmonary alveolar infiltrates on thoracic radiographs was performed before (PRE) and after (POST) sildenafil therapy. Clinical scores, pulmonary alveolar infiltrate scores and tricuspid regurgitation gradients were analyzed PRE and POST sildenafil. Pulmonary alveolar infiltrates associated with pulmonary hypertension developed in a diffusely patchy distribution (10/10). Sixty percent of dogs had a suspected diagnosis of interstitial pulmonary fibrosis as the etiology of pulmonary hypertension. Median PRE clinical score was 4 (range: 3-4) compared to POST score of 0 (0-2) (p = 0.005). Median alveolar infiltrate score PRE was 10 (5-12) compared to POST score of 4 (0-6) (p = 0.006). Median tricuspid regurgitation gradient PRE was 83 mmHg (57-196) compared to 55 mmHg POST (33-151) (p = 0.002). A subset of dogs with moderate to severe pulmonary hypertension present with diffuse, patchy alveolar infiltrates consistent with non-cardiogenic pulmonary edema. The typical clinical presentation is acute dyspnea and syncope, often in conjunction with heart murmurs suggestive of valvular insufficiency. This constellation of signs may lead to an initial misdiagnosis of congestive heart failure or pneumonia; however, these dogs clinically and radiographically improve with the initiation of sildenafil. Copyright © 2015 Elsevier B.V. All rights reserved.
Interstitial pneumonia associated to peginterferon alpha-2a: A focus on lung function
Cortés-Telles, Arturo
2016-01-01
Pulmonary toxicity related to the use of pegylated interferon alpha-2a during treatment of hepatitis C infections is rare; nonetheless, some cases with fatal outcomes have been reported. Evaluating patients’ pulmonary function is a key to diagnosis, follow-up and prognosis of several respiratory diseases, but case reports of respiratory manifestations related to the use of pegylated interferon alpha-2a have limited their findings to only baseline measurements. This paper examines the case of a 65-year-old woman with chronic hepatitis C virus infection who developed interstitial pneumonitis associated with pegylated interferon alpha-2a. Initial lung function evaluation revealed a marked reduction compared to an earlier assessment; the results were consistent with a moderate restricted pattern. Fortunately, over the ensuing 8 weeks of follow-up after discontinuing the drug, the patient recovered her lung function and experienced an overall improvement in her respiratory symptoms. PMID:27051119
Orchitis and Epididymitis in Koalas (Phascolarctos cinereus) Infected With Chlamydia pecorum.
Johnston, S D; Deif, H H; McKinnon, A; Theilemann, P; Griffith, J E; Higgins, D P
2015-11-01
Although Chlamydia causes disease of the urethra and prostate of male koalas, its impact on the testis and epididymis has not been examined. This study describes chronic-active and granulomatous orchitis and epididymitis with interstitial fibrosis associated with infection by Chlamydia pecorum in 2 of 18 adult male koalas being euthanized at a koala hospital, 8 of which also had chlamydial prostatitis. By immunohistochemistry and transmission electron microscopy, chlamydial inclusions were demonstrated within Sertoli cells directly associated with mild inflammation surrounding intact seminiferous and epididymal tubules, marked pyogranulomatous inflammation around disrupted tubules, replacement of tubules by interstitial fibrosis, and aspermia. The presence of C. pecorum but not Chlamydia pneumoniae was detected by quantitative polymerase chain reaction of formalin-fixed tissues of the left and right testes and right epididymis in 1 animal. This is the first report of orchitis and epididymitis in a koala infected with C. pecorum. © The Author(s) 2015.
Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.
Kanoh, Soichiro; Kobayashi, Hideo; Motoyoshi, Kazuo
2005-10-01
Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p < 0.001). Serial measurements revealed that increase and decrease of ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels < 5.0 pmol/dL remained stable or improved. Exhaled ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p < 0.01). Exhaled ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.
Johnson, Cheilonda
2017-05-01
To provide an overview of recently published articles covering interstitial lung disease associated with rheumatoid arthritis (RA-ILD). Over the past year, many studies replicated previous findings in more diverse and occasionally larger populations internationally. Specifically, the association among cigarette smoking, high rheumatoid factor titer, elevated anticitrullinated protein antibody (ACPA) levels, and RA-ILD was strengthened. Clinical characteristics, autoantibodies, and biomarkers to aid in RA-ILD development, progression, and mortality prediction were explored. Finally, direct and indirect treatment effects were highlighted. The ability to identify risk factors for preclinical RA-ILD has been enhanced, but the proper management strategy for these patients is yet to be defined. ACPAs and cigarette smoking are highly associated with RA-ILD, but the mechanistic relationship between lung injury and autoantibody generation remains unknown. There is conflicting evidence regarding the significance of a usual interstitial pneumonia (UIP) versus non-UIP pattern on high-resolution computed tomography. The use of biologic agents in patients with rheumatoid arthritis does not appear to increase the risk of incident ILD or RA-ILD exacerbation. Randomized prospective studies of specific therapy for RA-ILD are still lacking.
Nepheline rock dust pneumoconiosis. A report of 2 cases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Olscamp, G.; Herman, S.J.; Weisbrod, G.L.
1982-01-01
Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy, air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.
Nepheline rock dust pneumoconiosis: a report of 2 cases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Olscamp, G.; Herman, S.J.; Weisbrod, G.L.
1982-01-01
Two cases of nepheline rock dust pneumoconiosis are presented. Radiologically, this is seen as a diffuse increase in interstitial lung markings, lymphadenopathy air-space disease, and atelectasis secondary to extrinsic compression by enlarged hilar lymph nodes. Major differential diagnoses include carcinoma of the lung, sarcoidosis, and interstitial lung disease caused by other inorganic dusts. Nepheline rock dust pneumoconiosis should be considered when the above radiological changes are observed and an occupational exposure to inorganic dust is documented.
Imipenem/cilastatin-induced acute eosinophilic pneumonia.
Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei
2016-03-04
Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. 2016 BMJ Publishing Group Ltd.
Stethoscope vs. ultrasound probe - which is more reliable in children with suspected pneumonia?
Lovrenski, Jovan; Petrović, Slobodanka; Balj-Barbir, Svetlana; Jokić, Radoica; Vilotijević-Dautović, Gordana
2016-05-01
To compare lung ultrasound (LUS) with auscultation findings in children with clinical suspicion of pneumonia. A prospective study including 95 patients (age: from 2 months to 17.5 years; mean age: 5.1 y, SD 4.5 y) with referral diagnosis of suspected pneumonia. In all patients LUS and auscultatory examinations were performed within an hour. These findings were compared separately in each hemithorax. The radiologist performing LUS was blinded to the patient's clinical information. Positive auscultatory findings included: crackles and/or abnormal breath sounds (decreased, asymmetric, absent, or bronchial). For LUS examinations a combined transthoracic - transabdominal approach was used. A pneumonia-positive LUS finding included subpleural consolidation with air-bronchogram, or an adjacent area of interstitial edema. For each subpleural consolidation the cranio-caudal (CC) diameter was measured, and 95% confidence intervals (CI) of the sizes of subpleural consolidations for positive and negative auscultatory findings were compared. The p-value between LUS and auscultation was calculated using McNemar's test. LUS and auscultation showed pneumonia-positive findings in 98 and 64 hemithoraces, i.e. in 67 and 45 patients respectively. In positive auscultatory findings the CI for CC diameters of subpleural consolidations ranged from 32.46 to 54.14 mm, and in negative auscultatory findings the CI was between 16.52 and 29.83 mm, which showed a statistically significant difference. McNemar's test showed a statistically significant difference between LUS and auscultation. LUS showed positive findings in more hemithoraces than auscultation in children with suspected pneumonia. A cranio-caudal size of subpleural consolidation of less than 30 mm significantly reduces the possibility of auscultatory detection. Copyright © 2016 by Academy of Sciences and Arts of Bosnia and Herzegovina.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schrof, Julian; Müller, Ralph; Reedy, Robert C.
2015-07-28
Boron diffusivity reduction in extrinsically doped silicon was investigated in the context of a process combination consisting of BBr3 furnace diffusion and preceding Phosphorus ion implantation. The implantation of Phosphorus leads to a substantial blocking of Boron during the subsequent Boron diffusion. First, the influences of ion implantation induced point defects as well as the initial P doping on B diffusivity were studied independently. Here, it was found that not the defects created during ion implantation but the P doping itself results in the observed B diffusion retardation. The influence of the initial P concentration was investigated in more detailmore » by varying the P implantation dose. A secondary ion mass spectrometry (SIMS) analysis of the BSG layer after the B diffusion revealed that the B diffusion retardation is not due to potential P content in the BSG layer but rather caused by the n-type doping of the crystalline silicon itself. Based on the observations the B diffusion retardation was classified into three groups: (i) no reduction of B diffusivity, (ii) reduced B diffusivity, and (iii) blocking of the B diffusion. The retardation of B diffusion can well be explained by the phosphorus doping level resulting in a Fermi level shift and pairing of B and P ions, both reducing the B diffusivity. Besides these main influences, there are probably additional transient phenomena responsible for the blocking of boron. Those might be an interstitial transport mechanism caused by P diffusion that reduces interstitial concentration at the surface or the silicon/BSG interface shift due to oxidation during the BBr3 diffusion process. Lifetime measurements revealed that the residual (non-blocked) B leads to an increased dark saturation current density in the P doped region. Nevertheless, electrical quality is on a high level and was further increased by reducing the B dose as well as by removing the first few nanometers of the silicon surface after the BBr3 diffusion« less
Mohd Nasir, Mohd Desa; Parasakthi, Navaratnam
2004-06-01
The increasing prevalence of penicillin-resistant Streptococuus pneumoniae urges for fast and accurate susceptibility testing methods. This study evaluated the comparability of three commonly used techniques; disk diffusion, E-test and agar dilution, to detect penicillin susceptibility in clinical isolates of S. pneumoniae. Fifty pneumococcal isolates, obtained from patients at the University of Malaya Medical Centre, were selected to include both penicillin-susceptible strains and those that had decreased susceptibility (resistant and intermediate) to penicillin. The minimum inhibitory concentration (MIC) values of penicillin to serve as the reference was determined by the agar dilution method in which, based on the MIC breakpoints recommended by the National Committee for Clinical Laboratory Standards (NCCLS), 27 strains had decreased susceptibility to penicillin with 17 strains resistant and 10 intermediate. Comparing to the agar dilution method, oxacillin disk diffusion test detected all strains with decreased penicillin susceptibility as such while E-test showed a close agreement of susceptibility (92%) of the isolates to penicillin. This confirmed that oxacillin is a good screening test for S. pneumoniae isolates with decreased susceptibility to penicillin while E-test is very reliable for rapid and accurate detection of penicillin susceptibility.
Electrode assembly for use in a solid polymer electrolyte fuel cell
Raistrick, Ian D.
1989-01-01
A gas reaction fuel cell may be provided with a solid polymer electrolyte membrane. Porous gas diffusion electrodes are formed of carbon particles supporting a catalyst which is effective to enhance the gas reactions. The carbon particles define interstitial spaces exposing the catalyst on a large surface area of the carbon particles. A proton conducting material, such as a perfluorocarbon copolymer or ruthenium dioxide contacts the surface areas of the carbon particles adjacent the interstitial spaces. The proton conducting material enables protons produced by the gas reactions adjacent the supported catalyst to have a conductive path with the electrolyte membrane. The carbon particles provide a conductive path for electrons. A suitable electrode may be formed by dispersing a solution containing a proton conducting material over the surface of the electrode in a manner effective to coat carbon surfaces adjacent the interstitial spaces without impeding gas flow into the interstitial spaces.
Dukhin, Stanislav S.; Labib, Mohamed E.
2016-01-01
Current drug delivery devices (DDD) are mainly based on the use of diffusion as the main transport process. Diffusion-driven processes can only achieve low release rate because diffusion is a slow process. This represents a serious obstacle in the realization of recent successes in the suppression of lymphatic metastasis and in the prevention of limb and organ transplant rejection. Surprisingly, it was overlooked that there is a more favorable drug release mode which can be achieved when a special DDD is implanted near lymphatics. This opportunity can be realized when the interstitial fluid flow penetrates a drug delivery device of proper design and allows such fluid to flow out of it. This design is based on hollow fibers loaded with drug and whose hydrodynamic permeability is much higher than that of the surrounding tissue. The latter is referred to as hollow fiber of high hydrodynamic permeability (HFHP). The interstitial flow easily penetrates the hollow fiber membrane as well as its lumen with a higher velocity than that in the adjacent tissue. The interstitial liquid stream entering the lumen becomes almost saturated with drug as it flows out of the HFHP. This is due to the drug powder dissolution in the lumens of HFHP which forms a strip of drug solution that crosses the interstitium and finally enters the lymphatics. This hydrodynamically-driven release (HDR) may exceed the concomitant diffusion-driven release (DDR) by one or even two orders of magnitude. The hydrodynamics of the two-compartment media is sufficient for developing the HDR theory which is detailed in this paper. Convective diffusion theory for two compartments (membrane of hollow fiber and adjacent tissue) is required for exact quantification when a small contribution of DDR to predominating HDR is present. Hence, modeling is important for HDR which would lead to establishing a new branch in physico-chemical hydrodynamics. The release rate achieved with the use of HFHP increases proportional to the number of hollow fibers in the fabric employed in drug delivery. Based on this contribution, it is now possible to simultaneously provide high release rates and long release durations, thus overcoming a fundamental limitation in drug delivery. Perhaps this breakthrough in long-term drug delivery has potential applications in targeting lymphatics and in treating cancer and cancer metastasis without causing the serious side effects of systemic drugs. PMID:28579697
[My hybrid carrier of clinical pathologist].
Honda, Takayuki
2011-03-01
In this review, I showed a brief summary of my carrier in multiple special fields (clinical pathologist, anatomical pathologist of lung, respiratory physician and infection control doctor), my studies and my own view of laboratory medicine. We chiefly study pathology of the lung, especially about type II pneumocytes. Type II pneumocytes had abundant surface coat on the apical surface containing a specific carbohydrate structure of Thomsen-Friedenreich (TF) antigen. TF antigen is a marker of type II pneumocytes beyond animal species, and can be used for evaluating activity of various interstitial pneumonia as type II pneumocyte index (number/lmm alveolar length). Three dimensional views generated from thick sections of ordinary processed paraffin blocks showed new information of normal and abnormal lung morphology. Type II pneumocytes linearly located along the elastic fibers forming framework of polygonal alveoli, and in usual interstitial pneumonia, destruction of these elastic fibers were observed. In Japan, roles of a clinical pathologist are not definite as a radiologist, and clinical laboratory in a hospital is recognized as a section only performing blood and chemical tests. Evaluation of the data and participation in diagnosis were not requested. In future, medical doctors devote themselves to treat patients, and clinical pathologists and laboratory technicians have to help the doctors in diagnostic process. Routine tests (blood and urine) are most frequently performed in clinical medicine, but the data are not adequately used. Therefore, a system is necessary for interpreting routine tests and reporting them to other medical staffs.
Hosoda, Chiaki; Baba, Tomohisa; Hagiwara, Eri; Ito, Hiroyuki; Matsuo, Norikazu; Kitamura, Hideya; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Ogura, Takashi
2016-07-01
Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) is occasionally positive in patients with usual interstitial pneumonia (UIP). However, the differences from idiopathic pulmonary fibrosis (IPF/UIP) have not been well documented. We aimed to clarify the clinical, radiological and pathological features of UIP associated with MPO-ANCA (ANCA/UIP). We retrospectively reviewed the medical records of 12 consecutive ANCA/UIP patients not manifesting microscopic polyangiitis and 108 IPF/UIP patients with no autoantibodies, both diagnosed by surgical lung biopsy. There was no significant difference in clinical background, laboratory results and pulmonary function tests between ANCA/UIP patients and IPF/UIP patients except for the percentage of bronchoalveolar lavage neutrophils. HRCT showed subpleural reticulation in both groups. Increased attenuation around honeycombing and cysts was significantly observed in ANCA/UIP. Pathologically, ANCA/UIP had more prominent inflammatory cell infiltration, lymphoid follicles with germinal centres and cellular bronchiolitis. During the disease course, three of 12 patients (25%) developed microscopic polyangiitis. Immunosuppressive treatment tended to be more effective in ANCA/UIP patients, and the survival time in ANCA/UIP patients tended to be longer than those with IPF/UIP. ANCA/UIP may be distinguishable from IPF/UIP with a combination of HRCT findings of increased attenuation around honeycombing and cysts and some of the characteristic pathological findings. In contrast to IPF/UIP, immunosuppressive treatment could be a therapeutic option for ANCA/UIP. © 2016 Asian Pacific Society of Respirology.
Pathology Image of the Month:Cough and Shortness of Breath in a Noncompliant Patient with HIV/AIDS.
Thomasson, Reggie; Dewenter, Tracy; McGoey, Robin R
2015-01-01
A 37- year-old man with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) was admitted to the intensive care unit following a four month history of progressive shortness of breath, productive cough, and flu-like symptoms. His HIV/AIDS was diagnosed at the age of 19 (CD4 count =15; viral load = 294,436 copies/ mL) and was complicated by hemodialysis-dependent, HIV-associated nephropathy, prior Pneumocystis pneumonia and known noncompliance with prescribed antiretroviral therapy. Chest film at admission was interpreted as diffuse bilateral interstitial and airspace opacities with a right sided layering density representative of laminar pleural effusion. Bacterial blood cultures were subsequently negative. A bronchoalveolar lavage was performed and an image from the cytologic cell block is seen above in Figure 1. The patient's respiratory status continued to deteriorate and he was converted to comfort care. Following death, an unlimited autopsy examination was requested by the family and authorized by the coroner. At autopsy, additional gross pathologic findings included 350ml of chylous appearing pleural fluid and serous ascites (700ml). Histopathology revealed intra-alveolar acute fibrinopurulent exudate, chronic pericarditis and end-stage nephropathy. Similar cells to those shown above in Figure 1 were identified in lung epithelium and in pancreatic acinar cells. Special stain for Pneumocystis was negative.
Effects of Molybdenum Addition on Hydrogen Desorption of TiC Precipitation-Hardened Steel
NASA Astrophysics Data System (ADS)
Song, Eun Ju; Baek, Seung-Wook; Nahm, Seung Hoon; Suh, Dong-Woo
2018-05-01
The hydrogen-trap states in TiC and MoC that have coherent interfaces with ferrite were investigated using first-principles calculation. The trapping sites of TiC were the interfaces and interstitial sites of ferrite. On the other hand, the trapping sites of MoC were ferrite interstitial sites; the interface had a negative binding energy with H. Thermal desorption analysis confirms that the amounts of diffusible hydrogen were significantly reduced by addition of Mo in Ti-bearing steel.
Chambers, Scott A; Gu, Meng; Sushko, Peter V; Yang, Hao; Wang, Chongmin; Browning, Nigel D
2013-08-07
Heteroepitaxial growth of Cr metal on Nb-doped SrTiO₃(001) is accompanied by Cr diffusion to interstitial sites within the first few atomic planes, an anchoring of the Cr film to the substrate, charge transfer from Cr to Ti, and metallization of the near-surface region, as depicted in the figure. The contact resistance of the resulting interface is exceedingly low. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
2015-09-21
and metal organic chemical vapor deposition (MOCVD) [18]. In the former case, carbon can contaminate the material during air exposure in standard... gallium . In addition, carbon can be found as a contaminant in the source gases or it can be etched off the susceptor that transfers heat to the substrate...split interstitial Figure 1: Split interstitials of carbon (yellow) and nitrogen (blue) surrounded by four gallium atoms (red). energy differences of
2014-10-01
fibrosis, interstitial lung diseases 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...cadherin-11 in scleroderma patients with interstitial lung disease . We have been working with our collaborators at UTHSC to identify and sera that...83% female, avg age 49, avg disease duration 2.5 years, 59% with diffuse SSc, 28% with ILD and avg skin score of 16 at enrollment). Since there is
NASA Astrophysics Data System (ADS)
Wen, Haohua; Semenov, A. A.; Woo, C. H.
2017-09-01
The many-body dynamics of a crystalline solid containing an interstitial solute atom (ISA) is usually interpreted within the one-particle approximation as a random walker hopping among trapping centers at periodic lattice sites. The corresponding mobility and diffusivity can be formulated based on the transition-state theory in the form of the Arrhenius law. Possible issues arising from the many-body nature of the dynamics may need to be understood and resolved both scientifically and technologically. Noting the congruence between the dynamics of the many-body and stochastic systems within the Mori-Zwanzig theory, we analyzed the dynamics of a model particle subjected to a saw-tooth potential in a noisy medium. The ISA mobility is found to be governed by two sources of dissipative friction: that which is produced by the scattering of lattice waves by the moving ISA (phonon wind), and that which is derived from the energy dissipation associated with overcoming the migration barrier screened by lattice waves (i.e., phonon screened). The many-body effect in both cases increases with temperature, so that the first component of the friction is important at high temperatures and the second component is important at low temperatures. A formulation built on this mechanistic structure of the dissipative friction requires the mobility and diffusivity to be expressed not only in terms of the migration enthalpy and entropy, but also of the phonon drag coefficient. As a test, the complex temperature dependence of the mobility and diffusivity of interstitial helium in BCC W obtained from molecular-dynamics simulation is very well reproduced.
Yago, Toru; Nishinarita, Makoto
2004-12-01
In 1996 36-year-old man was admitted into our hospital because of polyarthralgia, skin eruptions followed by multiple cutaneous ulcers, dry cough and elevation of C-reactive protein level. The finding of skin biopsy from left elbow was vasculitis. Chest CT showed linear interstitial shadow at bilateral dorsalis lungs. Transbronchial lung biopsy (TBLB) revealed marked infiltration of inflammatory cells in the bronchial walls and peripheral alveoli. In addition, eosinophils were not in branchoalveolar lavage (BAL) fluid. Moreover, video-assisted thoracic surgery (VATS) revealed organizing fibroblastic polyp and bronchiolitis obliterans at terminal bronchiole. We diagnosed his pneumonia as bronchiolitis obliterans organizing pneumonia (BOOP). Administration of oral prednisolone (40 mg/day) was begun and he experienced diminished BOOP and other clinical manifestations. Three years later he developed dry cough, dyspnea and digital ulcers again. Arterial blood gas analysis revealed marked hypoxemia and laboratory studies showed LDH (377 IU/ml) and CRP (8.27 mg/dl) levels were elevated. Chest CT pointed out an exacerbation of BOOP. Treatment with intravenous pulses methylprednisolone and oral prednisolone (60 mg/day) resulted in marked improvement of the clinical manifestations. We describe a rare case of vasculitis associated with BOOP.
Mori, Shunsuke; Sugimoto, Mineharu
2015-01-01
Pneumocystis jirovecii infection causes fulminant interstitial pneumonia (Pneumocystis pneumonia, PCP) in patients with rheumatoid arthritis (RA) who are receiving biological and/or nonbiological antirheumatic drugs. Recently, we encountered a PCP outbreak among RA outpatients at our institution. Hospital-acquired, person-to-person transmission appears to be the most likely mode of this cluster of P. jirovecii infection. Carriage of P. jirovecii seems a time-limited phenomenon in immunocompetent hosts, but in RA patients receiving antirheumatic therapy, clearance of this organism from the lungs is delayed. Carriers among RA patients can serve as sources and reservoirs of P. jirovecii infection for other susceptible patients in outpatient facilities. Development of PCP is a matter of time in such carriers. Considering the poor survival rates of PCP cases, prophylactic antibiotics should be considered for RA patients who are scheduled to receive antirheumatic therapy. Once a new case of PCP occurs, we should take prompt action not only to treat the PCP patient but also to prevent other patients from becoming new carriers of P. jirovecii. Short-term prophylaxis with trimethoprim-sulfamethoxazole is effective in controlling P. jirovecii infection and preventing future outbreaks of PCP among RA patients. PMID:26396551
Average structure and local configuration of excess oxygen in UO(2+x).
Wang, Jianwei; Ewing, Rodney C; Becker, Udo
2014-03-19
Determination of the local configuration of interacting defects in a crystalline, periodic solid is problematic because defects typically do not have a long-range periodicity. Uranium dioxide, the primary fuel for fission reactors, exists in hyperstoichiometric form, UO(2+x). Those excess oxygen atoms occur as interstitial defects, and these defects are not random but rather partially ordered. The widely-accepted model to date, the Willis cluster based on neutron diffraction, cannot be reconciled with the first-principles molecular dynamics simulations present here. We demonstrate that the Willis cluster is a fair representation of the numerical ratio of different interstitial O atoms; however, the model does not represent the actual local configuration. The simulations show that the average structure of UO(2+x) involves a combination of defect structures including split di-interstitial, di-interstitial, mono-interstitial, and the Willis cluster, and the latter is a transition state that provides for the fast diffusion of the defect cluster. The results provide new insights in differentiating the average structure from the local configuration of defects in a solid and the transport properties of UO(2+x).
Herpes simplex infection in a juvenile orangutan (Pongo pygmaeus pygmaeus).
Kik, Maria J L; Bos, Jan H; Groen, Jan; Dorrestein, Gerry M
2005-03-01
A juvenile orangutan (Pongo pygmaeus pygmaeus) died after 8 days of diarrhea and vomiting. Necropsy showed petechial hemorrhages in the skin, the myocardium, and the peritoneal membranes. The lungs were hyperemic and edematous, and the liver and spleen were enlarged. Histologic changes consisted of interstitial pneumonia, hepatitis, and splenic hyperplasia. Numerous eosinophilic intranuclear inclusion bodies were visible in pulmonary epithelial cells, hepatocytes, and splenic endothelial cells. Electron microscopic examination revealed herpesvirus in hepatocyte nuclei. Polymerase chain reaction of liver tissue demonstrated the presence of a herpes simplex virus-1.
Sharp, Bryan L.; Peterson, Bonnie L.; Kus, Barbara E.
2005-01-01
A simple, papillary cystic adenocarcinoma of the mammary gland with metastases to the internal iliac and mesenteric lymph nodes, liver, and spleen was observed in a 12 to 13 year old female black-footed ferret (Mustela nigripes). Histologically, the tumor was aggressive, and lymphatic invasion was found. Attempts at virus isolation were negative. Other findings were bilateral infarcts in the kidneys, apparently resulting in acute renal shutdown and death, multiple thrombi in the right atrium, aortic arteriosclerosis, and focal interstitial pneumonia.
[Basic lung ultrasound. Part 2. Parenchymal diseases].
de la Quintana Gordon, F B; Nacarino Alcorta, B; Fajardo Pérez, M
2015-01-01
In this second part, an analysis is made of the pathology of lung parenchyma. This text is structured into different sections, including the study of atelectasias, pneumonia and abscess, interstitial/alveolar or Blines patterns, and finally an analysis is made of pulmonary embolism. With this second part, the basic knowledge to develop lung ultrasound in the anesthesia department has been presented. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.
Current understanding of point defects and diffusion processes in silicon
NASA Technical Reports Server (NTRS)
Tan, T. Y.; Goesele, U.
1985-01-01
The effects of oxidation of Si which established that vacancies (V) and Si self interstitials (I) coexist in Si at high temperatures under thermal equilibrium and oxidizing conditions are discussed. Some essential points associated with Au diffusion in Si are then discussed. Analysis of Au diffusion results allowed a determination of the I component and an estimate of the V component of the Si self diffusion coefficient. A discussion of theories on high concentration P diffusion into Si is then presented. Although presently there still is no theory that is completely satisfactory, significant progresses are recently made in treating some essential aspects of this subject.
Revisiting the diffusion mechanism of helium in UO2: A DFT+U study
NASA Astrophysics Data System (ADS)
Liu, X.-Y.; Andersson, D. A.
2018-01-01
The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO2 is revisited by using the DFT+U simulation methodology employing the "U-ramping" method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the "asymmetric hop" mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. The new mechanism is shown to be the dominant one over a wide temperature range.
NASA Astrophysics Data System (ADS)
Carroll, M. S.; Chang, C.-L.; Sturm, J. C.; Büyüklimanli, T.
1998-12-01
In this letter, we show the ability, through introduction of a thin Si1-x-yGexCy layer, to eliminate the enhancement of enhanced boron diffusion in silicon due to an oxidizing surface or ion implant damage. This reduction of diffusion is accomplished through a low-temperature-grown thin epitaxial Si1-x-yGexCy layer which completely filters out excess interstitials introduced by oxidation or ion implant damage. We also quantify the oxidation-enhanced diffusion (OED) and transient-enhanced diffusion (TED) dependence on substitutional carbon level, and further report both the observation of carbon TED and OED, and its dependence on carbon levels.
Williams, David; Kadaria, Dipen; Sodhi, Amik; Fox, Roy; Williams, Glenn; Threlkeld, Stephen
2017-04-05
BACKGROUND Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disease caused by a genetic defect in the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase enzyme, resulting in increased susceptibility to bacterial and fungal infections. The inheritance can be X-linked or autosomal recessive. Patients usually present with repeated infections early in life. We present an unusual case of a 23-year-old patient diagnosed with CGD. CASE REPORT A 23-year-old white woman with no previous history of recurrent infections presented with complaints of fever, shortness of breath, and diffuse myalgia. She had been treated twice for similar complaints recently, but without resolution. She was febrile, tachypneic, tachycardic, and hypoxic at presentation. Physical examination revealed diffuse inspiratory rales. Laboratory results showed leukocytosis. Her initial chest X-ray and CT chest showed reticular nodular interstitial lung disease pattern. Despite being on broad-spectrum antibiotics for 5 days, she continued to require supplemental oxygen and continued to be tachypneic, with minimal activity. Initial diagnostic tests, including bronchoscopy with biopsy and lavage, did not reveal a diagnosis. She then underwent a video-assisted thoracoscopic surgery (VATS) lung biopsy. The biopsy slides showed suppurative granulomatous inflammation affecting greater than 50% of the parenchymal lung surface. Fungal hyphae consistent with Aspergillus were present in those granulomas. A diagnosis of CGD was made and she was started on Voriconazole. She improved with treatment. Her neutrophil burst test showed negative burst on stimulation, indicating phagocytic dysfunction consistent with CGD. Autosomal recessive CGD was confirmed by genetic testing. CONCLUSIONS CGD can present in adulthood without any previous symptoms and signs. Clinicians should consider this disease in patients presenting with recurrent or non-resolving infections. Timely treatment and prophylaxis has been shown to reduce serious infections as well as mortality in these patients.
Update on the diagnosis and treatment of Pneumocystis pneumonia.
Carmona, Eva M; Limper, Andrew H
2011-02-01
Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk.
NASA Astrophysics Data System (ADS)
Faridah; Natalia; Lina, Maria; W, Hendig
2014-03-01
Suji (Pleomele angustifolia NE Brown) is one of the medicinal plants of the tribe of Liliaceae, empirically useful to treat coughs and respiratory diseases such as tuberculosis (TB) and pneumonia. In this study, ethanolic extract of suji leaves was tested its activity against bacteria that attacks the respiratory organs, namely Mycobacterium tuberculosis and Streptococcus pneumoniae, using a paper disc diffusion and dilution agar method. These extracts have activity in inhibiting the growth of M. tuberculosis at a concentration of 8 mg and against S. pneumoniae at a concentration of 4 mg. The fractions were tested their antibacterial activity against Streptococcus pneumoniae using paper disc diffusion method. The most active fraction was chosen based on the inhibition diameter. The fractions contained flavonoids, steroids, and essential oils. The precipitate isolated from the extraction process shows needle-shaped, white, cold and tasteless crystals. Moreover, the HPLC analysis of isolate revealed a single peak with a retention time of 7.183 minutes. The exact compounds in the isolate could not be determined but it was known the compounds contained the functional groups of alkene, alkane, C=O, -OH. Test results obtained from UV-Vis spectrophotometer provides maximum absorption at a wavelength of 203.0 nm.
Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi
2016-01-01
To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema.
Atomic diffusion in strain fields near solutes
NASA Astrophysics Data System (ADS)
Shropshire, Steven L.; Collins, Gary S.
1993-03-01
Annihilation reactions between mobile self-interstitial defects and complexes of vacancies with111In probe solutes in Au were studied. Measurements were made using the technique of perturbed angular correlations of gamma rays (PAC). Au samples were doped with complexes and plastically deformed at a low temperature to generate fluxes of self-interstitials. Changes in the concentrations of monovacancy (1V) to tetravacancy (4V) complexes induced by annihilation reactions were measured. These are now analysed using a system of coupled first-order equations in order to obtain interstitial annihilation cross sections of the complexes and the fractional amounts of different interstitial clusters in the flux. Relative cross sections obtained for Au are 1.0(1), 3.3(3), 1.2(2) and 7.5(2.5), respectively, for 1V to 4V complexes. The large increase in the cross sections with vacancy number is attributed to a progressive relaxation of the dilatational strain surrounding the oversized In solute as more vacancies are trapped. Also obtained from the analysis are values 0.34(5), 0.66(7), 0.0(1) and 0.0(2), respectively, for the fractions of mobile 1I to 4I clusters in deformed Au, indicating that di-interstitials are produced more readily than mono-interstitials during plastic deformation.
Anomalous Kinetics of Diffusion-Controlled Defect Annealing in Irradiated Ionic Solids.
Kotomin, Eugene; Kuzovkov, Vladimir; Popov, Anatoli I; Maier, Joachim; Vila, Rafael
2018-01-11
The annealing kinetics of the primary electronic F-type color centers (oxygen vacancies with trapped one or two electrons) is analyzed for three ionic materials (Al 2 O 3 , MgO, and MgF 2 ) exposed to intensive irradiation by electrons, neutrons, and heavy swift ions. Phenomenological theory of diffusion-controlled recombination of the F-type centers with much more mobile interstitial ions (complementary hole centers) allows us to extract from experimental data the migration energy of interstitials and pre-exponential factor of diffusion. The obtained migration energies are compared with available first-principles calculations. It is demonstrated that with the increase of radiation fluence both the migration energy and pre-exponent are decreasing in all three materials, irrespective of the type of irradiation. Their correlation satisfies the Meyer-Neldel rule observed earlier in glasses, liquids, and disordered materials.The origin of this effect is discussed. This study demonstrates that in the quantitative analysis of the radiation damage of real materials the dependence of the defect migration parameters on the radiation fluence plays an important role and cannot be neglected.
Sulfur doping of GaAs with (NH4)2Sx solution
NASA Astrophysics Data System (ADS)
Lee, Jong-Lam
1999-01-01
A novel technique for sulfur doping to GaAs was demonstrated. The surface of GaAs was treated with (NH4)2Sx solution, subsequent to annealing using either furnace or rapid thermal processing. Sulfur atoms adsorbed at the surface of GaAs during the (NH4)2Sx treatment diffuse into GaAs during the annealing. The diffusion profiles of sulfur in both types of annealing treatments show a concave shape from the GaAs surface. Diffusion constants of sulfur determined using the Boltzmann-Matano technique increase with the decrease of sulfur concentration via the depth from the surface of GaAs. This suggests that immobile sulfur donor SAs+ forms at the near surface interacts with a Ga divacancy, and results in the production of mobile As interstitials, IAs. The IAs moves fast toward the inside of GaAs and kickout the SAs+ donor, producing a fast diffusing species of interstitial S atoms. The diffusion coefficients of sulfur determined are 2.5×10-14 cm2/s at 840 °C and 5×10-12 cm2/s at 900 °C. The sulfur doping technique is applied to the fabrication of metal-semiconductor field-effect transistors (MESFETs). The MESFETs with 1.0 μm gate length exhibit transconductance of 190 mS/mm, demonstrating the applicability of this technique to the formation of active channel layer of MESFETs.
Parra, E.R.; Pincelli, M.S.; Teodoro, W.R.; Velosa, A.P.P.; Martins, V.; Rangel, M.P.; Barbas-Filho, J.V.; Capelozzi, V.L.
2014-01-01
Limitations on tissue proliferation capacity determined by telomerase/apoptosis balance have been implicated in pathogenesis of idiopathic pulmonary fibrosis. In addition, collagen V shows promise as an inductor of apoptosis. We evaluated the quantitative relationship between the telomerase/apoptosis index, collagen V synthesis, and epithelial/fibroblast replication in mice exposed to butylated hydroxytoluene (BHT) at high oxygen concentration. Two groups of mice were analyzed: 20 mice received BHT, and 10 control mice received corn oil. Telomerase expression, apoptosis, collagen I, III, and V fibers, and hydroxyproline were evaluated by immunohistochemistry, in situ detection of apoptosis, electron microscopy, immunofluorescence, and histomorphometry. Electron microscopy confirmed the presence of increased alveolar epithelial cells type 1 (AEC1) in apoptosis. Immunostaining showed increased nuclear expression of telomerase in AEC type 2 (AEC2) between normal and chronic scarring areas of usual interstitial pneumonia (UIP). Control lungs and normal areas from UIP lungs showed weak green birefringence of type I and III collagens in the alveolar wall and type V collagen in the basement membrane of alveolar capillaries. The increase in collagen V was greater than collagens I and III in scarring areas of UIP. A significant direct association was found between collagen V and AEC2 apoptosis. We concluded that telomerase, collagen V fiber density, and apoptosis evaluation in experimental UIP offers the potential to control reepithelization of alveolar septa and fibroblast proliferation. Strategies aimed at preventing high rates of collagen V synthesis, or local responses to high rates of cell apoptosis, may have a significant impact in pulmonary fibrosis. PMID:24919172
Wakiguchi, Hiroyuki; Hasegawa, Shunji; Hirano, Reiji; Kaneyasu, Hidenobu; Wakabayashi-Takahara, Midori; Ohga, Shouichi
2015-11-18
Macrophage activation syndrome (MAS) is the secondary hemophagocytic lymphohistiocytosis associated with rheumatic diseases. Recently, the different cytokine profiles between systemic juvenile idiopathic arthritis (sJIA)-associated MAS (sJIA-MAS) and juvenile systemic lupus erythematosus (JSLE)-associated MAS (JSLE-MAS) were reported. However, there is little information about juvenile dermatomyositis (JDM)-associated MAS (JDM-MAS). A 4-year-old girl with JDM was hospitalized because of fever, erythema, hepatosplenomegaly, cytopenia, liver dysfunction and coagulopathy. Bone marrow aspiration revealed appreciable numbers of activated and hemophagocytosing macrophages. She was diagnosed as having JDM-MAS complicated with interstitial pneumonia (IP) based on the findings of the elevation of serum Krebs von den Lungen-6 (KL-6) levels and chest computed tomography findings. We analyzed circulating levels of interleukin (IL)-2,4,6,10,18, tumor necrosis factor-α and interferon-γ in the patient. Hypercytokinemia occurred at the diagnosis of MAS and IP, showing with the prominent elevations of IL-6 and IL-18 levels. The cytokine profiles were distinct from those reported in patients with sJIA-MAS or JSLE-MAS. High-dose corticosteroid and cyclosporine therapy led to a drastic improvement of MAS with decreased IL-6 levels. Subsequent cyclophosphamide therapy successfully controlled IP, paralleled with the declining pattern of IL-18 and KL-6 levels. This is the first report to describe a successful treatment and the cytokine profile of JDM-MAS and IP. Serum IL-6 and IL-18 levels may be useful for predicting the disease activity of JDM-MAS and IP, respectively.
NASA Astrophysics Data System (ADS)
Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.
2017-03-01
A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.
Watanabe, Yasutaka; Kawabata, Yoshinori; Koyama, Nobuyuki; Ikeya, Tomohiko; Hoshi, Eishin; Takayanagi, Noboru; Koyama, Shinichiro
2017-08-01
The clinicopathological characteristics of lung cancer with concomitant usual interstitial pneumonia (UIP) are insufficiently understood. This study aimed to elucidate a characteristic pathological feature of lung cancer that develops in patients with UIP, with a focus on the location of its onset. We reviewed surgically obtained specimens, including 547 tumors from 526 patients who underwent lobectomy for lung cancer. Surveyed patients were classified into three groups: patients with UIP (UIP group), patients with lung pathology other than UIP (non-UIP group), and patients without any associated lung pathology (normal group). The histology as well as the lobe and location of the onset of lung cancer were compared among these groups. The peripheral location was subdivided into subpleural, inner and tumor involved centrally secondary to extension. The UIP group comprised 82 patients (male, 71 [87%]; mean age, 71 years; smoking rate, 94%), the non-UIP group comprised 334 patients (male, 267 [80%]; mean age, 69 years; smoking rate, 81%), and the normal group comprised 110 patients (male, 33 [30%]; mean age, 63; smoking rate, 29%). No statistical differences were noted in sex, mean age, or smoking index between the UIP and non-UIP groups. Compared with the non-UIP group, the frequency of squamous cell carcinoma (63% vs. 32%), lower lobe origin (76% vs. 32%), and subpleural location (24% vs. 5%) were significantly higher in the UIP group. Lung cancers in patients with UIP show a predilection for the subpleural region, where UIP is also thought to originate. Copyright © 2017 Elsevier Ltd. All rights reserved.
Body size-adjusted dose analysis of pirfenidone in patients with interstitial pneumonia.
Uehara, Masahiro; Enomoto, Noriyuki; Oyama, Yoshiyuki; Suzuki, Yuzo; Kono, Masato; Furuhashi, Kazuki; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Suda, Takafumi
2018-03-01
Pirfenidone is an effective anti-fibrotic agent for idiopathic pulmonary fibrosis (IPF). Although adverse events (AE) sometimes prevent patients from continuing treatment, current dose adjustment guidance does not consider patient body size or weight (BW). The aim of this study was to evaluate the importance of pirfenidone dose adjustment by body surface area (BSA) or BW for preventing AE and permitting continuous treatment in patients with interstitial pneumonia (IP). Sixty-seven Japanese patients with IP including 46 patients with IPF treated with pirfenidone between 2009 and 2015 were retrospectively evaluated. Pirfenidone doses were adjusted by BSA or BW and were compared with clinical parameters. Forty-two of 67 patients (62.7%) with IP showed AE, most commonly gastrointestinal symptoms (77.5%). Patients having AE received significantly higher adjusted doses of pirfenidone by both BSA and BW (P = 0.024 and P = 0.010, respectively), while unadjusted doses did not differ. BSA-adjusted dose discriminated patients with AE from those without (area under the curve = 0.666 at 1085 mg/m 2 ). Six of seven patients (85.7%) who discontinued pirfenidone due to AE took ≥1085 mg/m 2 of pirfenidone. In a subgroup with IPF, patients taking a medium dose (median: 876 median-1085 mg/m 2 ) showed a lower annual decline in % forced vital capacity than patients taking a lower dose (P = 0.025). BSA-adjusted pirfenidone dosing may be useful to prevent AE whilst achieving a long-term treatment effect in patients with IP. © 2017 Asian Pacific Society of Respirology.
Kose, Eiji
2018-03-25
Pregabalin is used for the relief of neuropathic pain in patients with and without cancer. However, no report has examined whether there is a difference in the adverse drug event (ADE) profile of pregabalin in each context. We aimed to establish whether pregabalin's ADE profile was different between patients with and without cancer. This study was based on the Japanese Adverse Drug Event Report (JADER) database, which is a spontaneous reporting database. Reports obtained from the JADER database were analysed from April 2004 to December 2016 for ADEs, using reporting odds ratios (RORs), a method of disproportionality analysis. We evaluated the association between the RORs and ADEs of pregabalin and compared the age, dosage and time at which ADEs occurred in patients with and without cancer. The primary outcome was RORs. Secondary outcomes were expression age and time-to-onset of ADE among patients with and without cancer. In total, 426 216 reports from the JADER database were analysed. The major side effects associated with pregabalin among both patient groups were interstitial pneumonia, renal failure, liver failure, altered consciousness, heart failure and rhabdomyolysis. The pregabalin dose was significantly higher in patients with cancer than in those without cancer. Furthermore, the times to reporting of interstitial pneumonia, altered consciousness and liver failure were significantly shorter in patients with cancer than in those without cancer. The ADE profiles of pregabalin were broadly similar among patients with and without cancer, but time-to-onset and type of some ADEs may be different. © 2018 John Wiley & Sons Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Schrof, Julian, E-mail: julian.schrof@ise.fraunhofer.de; Müller, Ralph; Benick, Jan
2015-07-28
Boron diffusivity reduction in extrinsically doped silicon was investigated in the context of a process combination consisting of BBr{sub 3} furnace diffusion and preceding Phosphorus ion implantation. The implantation of Phosphorus leads to a substantial blocking of Boron during the subsequent Boron diffusion. First, the influences of ion implantation induced point defects as well as the initial P doping on B diffusivity were studied independently. Here, it was found that not the defects created during ion implantation but the P doping itself results in the observed B diffusion retardation. The influence of the initial P concentration was investigated in moremore » detail by varying the P implantation dose. A secondary ion mass spectrometry (SIMS) analysis of the BSG layer after the B diffusion revealed that the B diffusion retardation is not due to potential P content in the BSG layer but rather caused by the n-type doping of the crystalline silicon itself. Based on the observations the B diffusion retardation was classified into three groups: (i) no reduction of B diffusivity, (ii) reduced B diffusivity, and (iii) blocking of the B diffusion. The retardation of B diffusion can well be explained by the phosphorus doping level resulting in a Fermi level shift and pairing of B and P ions, both reducing the B diffusivity. Besides these main influences, there are probably additional transient phenomena responsible for the blocking of boron. Those might be an interstitial transport mechanism caused by P diffusion that reduces interstitial concentration at the surface or the silicon/BSG interface shift due to oxidation during the BBr{sub 3} diffusion process. Lifetime measurements revealed that the residual (non-blocked) B leads to an increased dark saturation current density in the P doped region. Nevertheless, electrical quality is on a high level and was further increased by reducing the B dose as well as by removing the first few nanometers of the silicon surface after the BBr{sub 3} diffusion.« less
Children's Interstitial and Diffuse Lung Disease. Progress and Future Horizons.
Deterding, Robin R
2015-10-01
Children's interstitial and diffuse lung disease (chILD) is a term that encompasses a large and diverse group of rare pediatric diseases and disorders. Significant progress has been made over the last 2 decades in classification, clinical care, research, and organizational structure to enhance the care of children with these high-morbidity and -mortality diseases. New diseases have been defined clinically and genetically, classification systems developed and applied, organizations formed such as the chILD Research Network (chILDRN) and chILD Foundation, and basic and translational science expanded to focus on chILD diseases. Multidisciplinary collaborations and efforts to advance understanding and treatment of chILD have been extended worldwide. The future horizon holds great promise to expand scientific discoveries, collaborate more broadly, and bring new treatment to these children. An overview of key historical past developments, major clinical and research updates, and opportunities for the future in chILD is reviewed in this Perspective.
A Rate-Theory-Phase-Field Model of Irradiation-Induced Recrystallization in UMo Nuclear Fuels
NASA Astrophysics Data System (ADS)
Hu, Shenyang; Joshi, Vineet; Lavender, Curt A.
2017-12-01
In this work, we developed a recrystallization model to study the effect of microstructures and radiation conditions on recrystallization kinetics in UMo fuels. The model integrates the rate theory of intragranular gas bubble and interstitial loop evolutions and a phase-field model of recrystallization zone evolution. A first passage method is employed to describe one-dimensional diffusion of interstitials with a diffusivity value several orders of magnitude larger than that of fission gas xenons. With the model, the effect of grain sizes on recrystallization kinetics is simulated. The results show that (1) recrystallization in large grains starts earlier than that in small grains, (2) the recrystallization kinetics (recrystallization volume fraction) decrease as the grain size increases, (3) the predicted recrystallization kinetics are consistent with the experimental results, and (4) the recrystallization kinetics can be described by the modified Avrami equation, but the parameters of the Avrami equation strongly depend on the grain size.
Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity
NASA Technical Reports Server (NTRS)
Verbanck, S.; Larsson, H.; Linnarsson, D.; Prisk, G. K.; West, J. B.; Paiva, M.
1997-01-01
In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.
Ambroggio, Lilliam; Sucharew, Heidi; Rattan, Mantosh S; O'Hara, Sara M; Babcock, Diane S; Clohessy, Caitlin; Steinhoff, Mark C; Macaluso, Maurizio; Shah, Samir S; Coley, Brian D
2016-09-01
To determine the interrater reliability (IRR) of lung ultrasonography (LUS) and chest radiography (CXR) and evaluate the accuracy of LUS compared with CXR for detecting pediatric pneumonia compared with chest computed tomography (CT) scan. This was a prospective cohort study of children aged 3 months to 18 years with a CXR and LUS performed between May 1, 2012, and January 31, 2014 with or without a clinical diagnosis of pneumonia. Four pediatric radiologists blinded to clinical information reported findings for the CXR and LUS images. IRR was estimated for 50 LUS and CXR images. The main outcome was the finding from CT ordered clinically or the probability of the CT finding for patients clinically requiring CT. Two radiologists reviewed CT scans to determine an overall finding. Latent class analysis was used to evaluate the sensitivity and specificity for findings (eg, consolidation) for LUS and CXR compared with CT. Of the 132 patients in the cohort, 36 (27%) had CT performed for a clinical reason. Pneumonia was clinically documented in 47 patients (36%). The IRR for lung consolidation was 0.55 (95% CI, 0.40-0.70) for LUS and 0.36 (95% CI, 0.21-0.51) for CXR. The sensitivity for detecting consolidation, interstitial disease, and pleural effusion was statistically similar for LUS and CXR compared with CT; however, specificity was higher for CXR. The negative predictive value was similar for CXR and LUS. LUS has a sufficiently high IRR for detection of consolidation. Compared with CT, LUS and CXR have similar sensitivity, but CXR is more specific for findings indicating pneumonia. Copyright © 2016 Elsevier Inc. All rights reserved.
Corynebacterial pneumonia in an African hedgehog.
Raymond, J T; Williams, C; Wu, C C
1998-04-01
A 3-mo-old, male African hedgehog (Atelerix albiventris) was anorectic and lethargic for a period of 3 days prior to death. Necropys revealed lungs that were diffusely firm, dark red, and dorsally adhered by fibrinous tags to the pericardial sac. Histopathology revealed necrosuppurative bronchopneumonia with pulmonary abscesses and suppurative pericarditis and myocarditis. A Corynebacterium sp. was isolated from the lungs. We believe this is the first reported case of corynebacterial pneumonia in an African hedgehog.
Out-diffusion of deep donors in nitrogen-doped silicon and the diffusivity of vacancies
NASA Astrophysics Data System (ADS)
Voronkov, V. V.; Falster, R.
2012-07-01
A strong resistivity increase in annealed nitrogen-doped silicon samples was reported long ago—but has remained not fully understood. It is now shown that the complicated evolution of the resistivity depth profiles observed can be reproduced by a simple model based on the out-diffusion of some relevant species. Two versions of such an approach were analyzed: (A) out-diffusion of deep donors treated as VN (off-centre substitutional nitrogen), (B) out-diffusion of vacancies (V) and interstitial trimers (N3) produced by dissociation of VN3. Version B, although more complicated, is attractive due to a coincidence of the deduced vacancy diffusivity DV at 1000 °C with the value extrapolated from low-temperature data by Watkins.
Oxidation Resistant Ti-Al-Fe Diffusion Barrier for FeCrAlY Coatings on Titanium Aluminides
NASA Technical Reports Server (NTRS)
Brady, Michael P. (Inventor); Smialke, James L. (Inventor); Brindley, William J. (Inventor)
1996-01-01
A diffusion barrier to help protect titanium aluminide alloys, including the coated alloys of the TiAl gamma + Ti3Al (alpha2) class, from oxidative attack and interstitial embrittlement at temperatures up to at least 1000 C is disclosed. The coating may comprise FeCrAlX alloys. The diffusion barrier comprises titanium, aluminum, and iron in the following approximate atomic percent: Ti-(50-55)Al-(9-20)Fe. This alloy is also suitable as an oxidative or structural coating for such substrates.
Revisiting the diffusion mechanism of helium in UO 2 : A DFT+ U study
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu, X. -Y.; Andersson, D. A.
The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO 2 is revisited by using the DFT+U simulation methodology employing the “U-ramping” method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the “asymmetric hop” mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. We show that the new mechanism is the dominant one over a widemore » temperature range.« less
Revisiting the diffusion mechanism of helium in UO 2 : A DFT+ U study
Liu, X. -Y.; Andersson, D. A.
2017-11-03
The understanding of migration properties of helium atoms after their generation through α-decay of actinides in spent nuclear fuels is important for the safety of nuclear fuel storage and disposal. The diffusion of helium in UO 2 is revisited by using the DFT+U simulation methodology employing the “U-ramping” method to address the issue of metastable energy states. A novel diffusion mechanism by helium interstitials, the “asymmetric hop” mechanism, is reported and compared to other diffusion mechanisms including an oxygen vacancy mediated mechanism and available experimental diffusion data. We show that the new mechanism is the dominant one over a widemore » temperature range.« less
First principles study of hydrogen behaviors in hexagonal tungsten carbide
NASA Astrophysics Data System (ADS)
Kong, Xiang-Shan; You, Yu-Wei; Liu, C. S.; Fang, Q. F.; Chen, Jun-Ling; Luo, G.-N.
2011-11-01
Understanding the behaviors of hydrogen in hexagonal tungsten carbide (WC) is of particular interest for fusion reactor design due to the presence of WC in the divertor of fusion reactors. Here, we have used first principles calculations to study the hydrogen behavior in WC. It is found that the most stable interstitial site for the hydrogen atom is the projection of the octahedral interstitial site on tungsten basal plane, followed by the site near the projection of the octahedral interstitial site on carbon basal plane. The binding energy between two interstitial hydrogen atoms is negative, suggesting that hydrogen itself is not capable of trapping another hydrogen atoms to form hydrogen molecule. The calculated results on the interaction between hydrogen and vacancy indicate that hydrogen atom is preferably trapped by vacancy defects and hydrogen molecule can not be formed in mono-vacancy. In addition, the hydrogen atom bound to carbon is only found in tungsten vacancy. We also study the migrations of hydrogen in WC and find that the interstitial hydrogen atom prefers to diffuse along the c-axis. Our studies provide some explanations for the results of the thermal desorption process of energetic hydrogen ion implanted into WC.
Ventilation-perfusion matching during exercise
NASA Technical Reports Server (NTRS)
Wagner, P. D.
1992-01-01
In normal subjects, exercise widens the alveolar-arterial PO2 difference (P[A-a]O2) despite a more uniform topographic distribution of ventilation-perfusion (VA/Q) ratios. While part of the increase in P(A-a)O2 (especially during heavy exercise) is due to diffusion limitation, a considerable amount is caused by an increase in VA/Q mismatch as detected by the multiple inert gas elimination technique. Why this occurs is unknown, but circumstantial evidence suggests it may be related to interstitial pulmonary edema rather than to factors dependent on ventilation, airway gas mixing, airway muscle tone, or pulmonary vascular tone. In patients with lung disease, the gas exchange consequences of exercise are variable. Thus, arterial PO2 may increase, remain the same, or fall. In general, patients with advanced chronic obstructive pulmonary disease (COPD) or interstitial fibrosis who exercise show a fall in PO2. This is usually not due to worsening VA/Q relationships but mostly to the well-known fall in mixed venous PO2, which itself results from a relatively smaller increase in cardiac output than VO2. However, in interstitial fibrosis (but not COPD), there is good evidence that a part of the fall in PO2 on exercise is caused by alveolar-capillary diffusion limitation of O2 transport; in COPD (but not interstitial fibrosis), a frequent additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that minute ventilation does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and PO2 to fall.
[Imaging origins and characteristics analysis of acute and chronic aspiration pneumonia].
Wang, Kang; Li, Ming; Wang, Xiongbiao; Qin, Jianmin; Wang, Zhi; Zhao, Zehua; Qin, Le; Hua, Yanqing
2014-11-11
To discuss about the pathologic and imaging origins and characteristics of CT scaning and X-ray radiography for acute and chronic aspiration pneumonia. Imaging data from 30 patients with aspiration pneumonia were retrospectively analyzed, CT scaning was performed in 27 patients, which PMVR reconstruction was performed in 21 cases;3 exammed by X-ray with 2 used by esophagography. Opaque bodies were detected in trachea by CT scaning in 12 patients.7 patients in acute phase rapidly developed into acute respiratory distress syndrome(ARDS). CT signs of 30 patients with acute and chronic aspiration pneumonia included: centrilobular nodules were detected in 2 cases with acute phase, 4 cases with subacute phase and 4 cases with chronic phase; the imaging of ground glass opacity were detected in 9 cases with acute phase, 2 cases with subacute phase and 3 cases with chronic phase; the imaging of bronchiectasis was detected in 8 cases with chronic phase, which mucilage embolism was detected in 3 of 8 cases; the imaging of atelectasis was detected in 6 cases with chronic phase; the imaging of sheeted consolidation was detected in 5 cases with chronic phase, 8 case with acute phase; the imaging of interstitial fibrosis was detected in 3 cases with chronic phase. Lesions of inferior lobe of right lung were detected in 9 cases with chronic phase, 4 cases with subacute phase, 11 case with acute phase;lesions of inferior lobe of left lung were detected in 6 cases with chronic phase and 3 cases with subacute group, 11 case with acute phase. The imaging features of acute and chronic aspiration pneumonia overlap with GGO and centrilobular nodules in every group. While the imaging features of atelectasis, bronchiectasis or mucilage embolism are found in chronic phase. The chest CT scaning may accurately evaluate the dynamic change of aspiration pneumonia.
Thurber, Mary Irene; Gjeltema, Jenessa; Sheley, Matthew; Wack, Ray F
2017-09-01
A 10-year-old male castrated red kangaroo (Macropus rufus) presented with mandibular swelling. Examination findings included pitting edema with no dental disease evident on examination or radiographs. The results of blood work were moderate azotemia, hypoalbuminemia, and severely elevated urine protein:creatinine ratio (9.9). Radiographs showed an interstitial pattern of the caudal right lung, and an abdominal ultrasound demonstrated scant effusion. Symptomatic and empirical therapy with antibiotics, anti-inflammatory drugs, and an angiotensin-converting enzyme (ACE) inhibitor did not resolve clinical signs. Due to poor prognosis and declining quality of life, euthanasia was elected. Necropsy revealed chronic granulomatous pneumonia of the caudal right lung lobe with intralesional Cryptococcus, identified as C. neoformans var. grubii by DNA sequencing. Severe bilateral glomerular and tubulointerstitial amyloidosis induced protein-losing nephropathy, leading to tri-cavitary effusion, subcutaneous edema, and cachexia. The authors speculate that renal amyloidosis was associated with chronic cryptococcal pneumonia in this red kangaroo.
Chronic eosinophilic pneumonia.
Fox, B; Seed, W A
1980-01-01
We described three cases of eosinophilic pneumonia of unknown aetiology investigated clinically and by lung biopsy. The illnesses lasted between six and 20 weeks and consisted of cough, dyspnoea, malaise, and in two cases prolonged pyrexia. All had blood eosinophilia and chest radiographs showing widespread bilateral shadowing; in two cases this had a characteristic peripheral distribution. One patient recovered spontaneously and the other two responded to steroids, with disappearance of pyrexia within 12 hours and radiological clearing within 14 days. Lung function tests during the acute illness showed volume restriction or gas transfer defects or both in two cases. After remission all three showed abnormalities if small airways function. Lung biopsies performed during the acute illness were examined histologically and by transmission electron microscopy, and in two cases by immunofluorescence. There was both intra-alveolar and interstitial eosinophilic pneumonia with bronchiolitis obliterans, microgranulomata, and a vasculitis. Electron microscopy showed numerous eosinophils, many degranulated, and macrophages with phagocytosed eosinophilic granules and intracytoplasmic inclusions. In one case IgM, IgG, and IgA were demonstrated in the bronchial walls and interstitium. No IgE or complement was present. We believe that eosinophil granules are responsible for the tissue damage and fever and suggest mechanisms for this and for the response to steroid therapy. Images PMID:7003796
Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Rahaghi, Farbod N; Sanchez-Ferrero, Gonzalo Vegas; Putman, Rachel K; Hunninghake, Gary M; Onieva, Jorge Onieva; Martinez, Fernando J; Choi, Augustine M; Bowler, Russell P; Lynch, David A; Hatabu, Hiroto; Bhatt, Surya P; Dransfield, Mark T; Wells, J Michael; Rosas, Ivan O; San Jose Estepar, Raul; Washko, George R
2018-06-05
Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality. © RSNA, 2018 Online supplemental material is available for this article.
Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi
2012-01-01
Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement. PMID:22184467
Kanai, Yoshihiko; Endo, Shunsuke; Tetsuka, Kenji; Yamamoto, Shinichi
2012-03-01
Reinforced endostapling can prevent postoperative air leakage from surgical stumps. We herein present a 58-year old woman with idiopathic interstitial pneumonia who developed lethal haemothorax after a thoracoscopic lung biopsy with the use of an endostapler preloaded with bioabsorbable tissue reinforcement material. This lethal haemothorax, which occurred on the day after the lung biopsy, required an emergency operation. The bleeding point was an intercostal artery of the inferior chest wall adjacent to the surgical stump. The operative findings suggested that the reinforced material on the surgical stump scratched the chest wall through respiratory movement.
Update on diagnosis and treatment of idiopathic pulmonary fibrosis
Baddini-Martinez, José; Baldi, Bruno Guedes; da Costa, Cláudia Henrique; Jezler, Sérgio; Lima, Mariana Silva; Rufino, Rogério
2015-01-01
Idiopathic pulmonary fibrosis is a type of chronic fibrosing interstitial pneumonia, of unknown etiology, which is associated with a progressive decrease in pulmonary function and with high mortality rates. Interest in and knowledge of this disorder have grown substantially in recent years. In this review article, we broadly discuss distinct aspects related to the diagnosis and treatment of idiopathic pulmonary fibrosis. We list the current diagnostic criteria and describe the therapeutic approaches currently available, symptomatic treatments, the action of new drugs that are effective in slowing the decline in pulmonary function, and indications for lung transplantation. PMID:26578138
[Comprehensive characteristics of the pulmonary syndrome in chronic liver diseases].
Pashchenko, I G; Romanov, A A; Zhumanbaeva, R M; Osmolovskiĭ, V S; Faliushina, N V
1988-01-01
Combined investigations have shown that the pulmonary syndrome in chronic liver diseases is a group of changes (heterogeneous in their structure and origin), most of which are of intercurrent nature (chronic bronchitis and its complications, chronic pneumonia), the lesser part of them is related directly to an inflammatory liver process and constitutes the true pulmonary syndrome (interstitial pneumonitis, fibrosing alveolitis). In view of the fact that chronic liver pathology is attended by concomitant disorders of pulmonary ventilation, hemodynamics and immunologic homestasis, the authors propose that they should be regarded as a risk factor contributing to the development of respiratory diseases.
Sauret, J; Casán, P
1980-03-25
Gastroesophageal diseases with reflux can cause numerous pulmonary complications (bronchospasm crisis, bronchitis, pneumonias, lung abscesses). These manifestations are very frequent in the hiatal hernias and in some series have reached up to 46 percent of the cases studied. Recently it has been suggested that microaspirations, repeated over a long period of time, may cause an alteration of the pulmonary interstitium and the consecutive development of a clinical and roentgenologic picture similar to pulmonary fibrosis. The aspirations are produced more frequently at night, favoured by the lying down position and because of it the patients present attacks of nocturnal cough. In this paper, two patients who presented the association of pulmonary fibrosis and hiatal hernia with esophageal relux are described. The first case was diagnosed early; he had minimal radiographic anomalies and the disappearance of the respiratory symptomatology was achieved by means of the medical treatment of the esophageal reflux. The second case was in a very advanced stage with severe respiratory insufficiency and gastrointestinal manifestations of many years' evolution. Both patients had been diagnosed as having idiopathic pulmonary fibrosis. Although there is no experimental proof of the "reflux-fibrosis" theory, we think that this possibility should be kept in mind before diagnosing the interstitial pulmonary pattern as idiopathic, especially in the cases of only slight radiographic and functional involvement susceptible to improvement with correction of the esophageal reflux.
NASA Astrophysics Data System (ADS)
Dardano, P.; Caliò, A.; Politi, J.; Di Palma, V.; Bevilacqua, M. F.; Rea, I.; Casalino, M.; Di Matteo, A.; Rendina, I.; De Stefano, L.
2015-06-01
Microneedles are newly developed biomedical devices, whose advantages are mainly in the non-invasiveness, discretion and versatility of use both as diagnostics and as therapeutics tool. In fact, they can be used both for drugs delivery in the interstitial fluids and for the analysis of the interstitial fluid. In this work we present the preliminary results for two devices based on micro needles in PolyEthylene (Glycol). The first for the drugs delivery includes a membrane whose optical reflected wavelength is related to the concentration of drug. Here, we present our preliminary result in diffusion of drugs between the membrane and the microneedles. The second device is gold coated and it works as electrode for the electrochemical detection of species in the interstitial fluid. A preliminary result in detection of glucose will be shown.
Diffusion of vaporous guests into a seemingly non-porous organic crystal
DOE Office of Scientific and Technical Information (OSTI.GOV)
Herbert, Simon A.; Janiak, Agnieszka; Thallapally, Praveen K.
2014-10-07
In this research, the tetragonal apohost phase of p-tert-butyltetramethoxythiacalix[4]arene absorbs hydrochloric acid and iodine. These guest molecules occupy different sites in the solid-state structure -- either within the small intrinsic voids of the macrocycle or within the interstitial spaces between the host molecules. This study illustrates the dynamic deformation of the host, providing strong mechanistic insight into the diffusion of guests into this seemingly non-porous material.
NASA Astrophysics Data System (ADS)
Grabtchak, Serge; Montgomery, Logan G.; Whelan, William M.
2014-05-01
We demonstrated the application of relative radiance-based continuous wave (cw) measurements for recovering absorption and scattering properties (the effective attenuation coefficient, the diffusion coefficient, the absorption coefficient and the reduced scattering coefficient) of bulk porcine muscle phantoms in the 650-900 nm spectral range. Both the side-firing fiber (the detector) and the fiber with a spherical diffuser at the end (the source) were inserted interstitially at predetermined locations in the phantom. The porcine phantoms were prostate-shaped with ˜4 cm in diameter and ˜3 cm thickness and made from porcine loin or tenderloin muscles. The described method was previously validated using the diffusion approximation on simulated and experimental radiance data obtained for homogenous Intralipid-1% liquid phantom. The approach required performing measurements in two locations in the tissue with different distances to the source. Measurements were performed on 21 porcine phantoms. Spectral dependences of the effective attenuation and absorption coefficients for the loin phantom deviated from corresponding dependences for the tenderloin phantom for wavelengths <750 nm. The diffusion constant and the reduced scattering coefficient were very close for both phantom types. To quantify chromophore presence, the plot for the absorption coefficient was matched with a synthetic absorption spectrum constructed from deoxyhemoglobin, oxyhemoglobin and water. The closest match for the porcine loin spectrum was obtained with the following concentrations: 15.5 µM (±30% s.d.) Hb, 21 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The tenderloin absorption spectrum was best described by 30 µM Hb (±30% s.d), 19 µM (±30% s.d.) HbO2 and 0.3 (±30% s.d.) fractional volume of water. The higher concentration of Hb in tenderloin was consistent with a dark-red appearance of the tenderloin phantom. The method can be applied to a number of biological tissues and organs for interstitial optical interrogation.
Le, Kelvin; Li, Xiaosong; Figueroa, Daniel; Towner, Rheal A.; Garteiser, Philippe; Saunders, Debra; Smith, Nataliya; Liu, Hong; Hode, Tomas; Nordquist, Robert E.; Chen, Wei R.
2011-01-01
Laser immunotherapy (LIT) uses a synergistic approach to treat cancer systemically through local laser irradiation and immunological stimulation. Currently, LIT utilizes dye-assisted noninvasive laser irradiation to achieve selective photothermal interaction. However, LIT faces difficulties treating deeper tumors or tumors with heavily pigmented overlying skin. To circumvent these barriers, we use interstitial laser irradiation to induce the desired photothermal effects. The purpose of this study is to analyze the thermal effects of interstitial irradiation using proton resonance frequency (PRF). An 805-nm near-infrared laser with an interstitial cylindrical diffuser was used to treat rat mammary tumors. Different power settings (1.0, 1.25, and 1.5 W) were applied with an irradiation duration of 10 min. The temperature distributions of the treated tumors were measured by a 7 T magnetic resonance imager using PRF. We found that temperature distributions in tissue depended on both laser power and time settings, and that variance in tissue composition has a major influence in temperature elevation. The temperature elevations measured during interstitial laser irradiation by PRF and thermocouple were consistent, with some variations due to tissue composition and the positioning of the thermocouple's needle probes. Our results indicated that, for a tissue irradiation of 10 min, the elevation of rat tumor temperature ranged from 8 to 11°C for 1 W and 8 to 15°C for 1.5 W. This is the first time a 7 T magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. Our work provides a basic understanding of the photothermal interaction needed to control the thermal damage inside a tumor using interstitial laser treatment. Our work may lead to an optimal protocol for future cancer treatment using interstitial phototherapy in conjunction with immunotherapy. PMID:22191937
Mechanism of anisotropic surface self-diffusivity at the prismatic ice-vapor interface.
Gladich, Ivan; Oswald, Amrei; Bowens, Natalie; Naatz, Sam; Rowe, Penny; Roeselova, Martina; Neshyba, Steven
2015-09-21
Predictive theoretical models for mesoscopic roughening of ice require improved understanding of attachment kinetics occurring at the ice-vapor interface. Here, we use classical molecular dynamics to explore the generality and mechanics of a transition from anisotropic to isotropic self-diffusivity on exposed prismatic surfaces. We find that self-diffusion parallel to the crystallographic a-axis is favored over the c-axis at sub-melt temperatures below about -35 °C, for three different representations of the water-water intermolecular potential. In the low-temperature anisotropic regime, diffusion results from interstitial admolecules encountering entropically distinct barriers to diffusion in the two in-plane directions. At higher temperatures, isotropic self-diffusion occurring deeper within the quasi-liquid layer becomes the dominant mechanism, owing to its larger energy of activation.
NASA Astrophysics Data System (ADS)
Nakamura, Minoru; Murakami, Susumu; Udono, Haruhiko
2018-03-01
We investigate the relationship between the intensity of band-edge (BDE) photoluminescence (PL) from 10 to 70 K and the concentration of iron diffused in boron-doped p-type silicon. Because of the nonradiative recombination activity of the interstitial iron-boron complex (FeiB center), the BDE-PL intensity at each temperature varies distinctively and systematically with the iron concentration, which means that this method has the potential to make the accurate measurements of a wide range of interstitial iron concentrations in silicon. The iron precipitates formed in the bulk and/or at the surface are found to exert much weaker recombination activity for excess carriers than FeiB center by exploiting both PL and deep-level transient spectroscopy (DLTS) measurements. The unexpected enhancement in BDE-PL intensity from iron-diffused silicon between 20 and 50 K is attributed to the passivation of the Si-oxide/Si interface by iron. For the samples diffused with trace amounts of iron, the iron concentration within 20 μm of the surface is significantly greater than that in the bulk, as measured by DLTS. This result is tentatively attributed to the affinity of iron with the Si-oxide.
Fabrication and characterization of cylindrical light diffusers comprised of shape memory polymer.
Small, Ward; Buckley, Patrick R; Wilson, Thomas S; Loge, Jeffrey M; Maitland, Kristen D; Maitland, Duncan J
2008-01-01
We developed a technique for constructing light diffusing devices comprised of a flexible shape memory polymer (SMP) cylindrical diffuser attached to the tip of an optical fiber. The devices are fabricated by casting an SMP rod over the cleaved tip of an optical fiber and media blasting the SMP rod to create a light diffusing surface. The axial and polar emission profiles and circumferential (azimuthal) uniformity are characterized for various blasting pressures, nozzle-to-sample distances, and nozzle translation speeds. The diffusers are generally strongly forward-directed and consistently withstand over 8 W of incident IR laser light without suffering damage when immersed in water. These devices are suitable for various endoluminal and interstitial biomedical applications.
Fabrication and characterization of cylindrical light diffusers comprised of shape memory polymer
Small, Ward; Buckley, Patrick R.; Wilson, Thomas S.; Loge, Jeffrey M.; Maitland, Kristen D.; Maitland, Duncan J.
2009-01-01
We developed a technique for constructing light diffusing devices comprised of a flexible shape memory polymer (SMP) cylindrical diffuser attached to the tip of an optical fiber. The devices are fabricated by casting an SMP rod over the cleaved tip of an optical fiber and media blasting the SMP rod to create a light diffusing surface. The axial and polar emission profiles and circumferential (azimuthal) uniformity are characterized for various blasting pressures, nozzle-to-sample distances, and nozzle translation speeds. The diffusers are generally strongly forward-directed and consistently withstand over 8 W of incident IR laser light without suffering damage when immersed in water. These devices are suitable for various endoluminal and interstitial biomedical applications. PMID:18465981
Genetics of Interstitial Lung Disease: Vol de Nuit (Night Flight)
Furukawa, Hiroshi; Oka, Shomi; Shimada, Kota; Tsuchiya, Naoyuki; Tohma, Shigeto
2015-01-01
Interstitial lung disease (ILD) is a chronic, progressive fibrotic lung disease with a dismal prognosis. ILD of unknown etiology is referred to as idiopathic interstitial pneumonia (IIP), which is sporadic in the majority of cases. ILD is frequently accompanied by rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), and other autoimmune diseases, and is referred to as collagen vascular disease-associated ILD (CVD-ILD). Susceptibility to ILD is influenced by genetic and environmental factors. Recent advances in radiographic imaging techniques such as high-resolution computed tomography (CT) scanning as well as high-throughput genomic analyses have provided insights into the genetics of ILD. These studies have repeatedly revealed an association between IIP (sporadic and familial) and a single nucleotide polymorphism (SNP) in the promoter region of the mucin 5B (MUC5B). HLA-DRB1*11 alleles have been reported to correlate with ILD in European patients with SSc, whereas in Japanese patients with RA, the HLA-DR2 serological group was identified. The aim of this review is to describe the genetic background of sporadic IIP, CVD-ILD, drug-induced-ILD (DI-ILD), pneumoconiosis, and hypersensitivity pneumonitis. The genetics of ILD is still in progress. However, this information will enhance the understanding of the pathogenesis of ILD and aid the identification of novel therapeutic targets for personalized medicine in future. PMID:26056507
Otani, Hideji; Tanaka, Tomonori; Murata, Kiyoshi; Fukuoka, Junya; Nitta, Norihisa; Nagatani, Yukihiro; Sonoda, Akinaga; Takahashi, Masashi
2016-01-01
Purpose To evaluate the incidence and pathologic correlation of thin-section computed tomography (TSCT) findings in smoking-related interstitial fibrosis (SRIF) with pulmonary emphysema. Patients and methods Our study included 172 consecutive patients who underwent TSCT and subsequent lobectomy. TSCT findings including clustered cysts with visible walls (CCVW) and ground-glass attenuation with/without reticulation (GGAR) were evaluated and compared in nonsmokers and smokers and among lung locations. TSCT findings, especially CCVW, were also compared with histological findings using lobectomy specimens. Results The incidence of CCVW and GGAR was significantly higher in smokers than in nonsmokers (34.1% and 40.7%, respectively, vs 2.0% and 12.2%). CCVW and GGAR were frequently found in the lower and peripheral zones. Histologically, CCVW corresponded more often with SRIF with emphysema than usual interstitial pneumonia (UIP, 63.3% vs 30%). CCVW of irregular size and shape were seen in 19 of 20 SRIF with emphysema and in seven of nine UIP-manifested areas with similar round cysts. A less-involved subpleural parenchyma was observed more frequently in SRIF with emphysema. Conclusion SRIF with emphysema is a more frequent pathological finding than UIP in patients with CCVW on TSCT. The irregular size and shape of CCVW and a less-involved subpleural parenchyma may be a clue suggesting the presence of SRIF with emphysema. PMID:27445472
Juge, Pierre-Antoine; Borie, Raphaël; Kannengiesser, Caroline; Gazal, Steven; Revy, Patrick; Wemeau-Stervinou, Lidwine; Debray, Marie-Pierre; Ottaviani, Sébastien; Marchand-Adam, Sylvain; Nathan, Nadia; Thabut, Gabriel; Richez, Christophe; Nunes, Hilario; Callebaut, Isabelle; Justet, Aurélien; Leulliot, Nicolas; Bonnefond, Amélie; Salgado, David; Richette, Pascal; Desvignes, Jean-Pierre; Lioté, Huguette; Froguel, Philippe; Allanore, Yannick; Sand, Olivier; Dromer, Claire; Flipo, René-Marc; Clément, Annick; Béroud, Christophe; Sibilia, Jean; Coustet, Baptiste; Cottin, Vincent; Boissier, Marie-Christophe; Wallaert, Benoit; Schaeverbeke, Thierry; Dastot le Moal, Florence; Frazier, Aline; Ménard, Christelle; Soubrier, Martin; Saidenberg, Nathalie; Valeyre, Dominique; Amselem, Serge; Boileau, Catherine; Crestani, Bruno; Dieudé, Philippe
2017-05-01
Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT , RTEL1 , PARN or SFTPC coding regions . The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT , RTEL1 , PARN or SFTPC mutations in RA-ILD patients (OR 3.17, 95% CI 1.53-6.12; p=9.45×10 -4 ). Telomeres were shorter in RA-ILD patients with a TERT , RTEL1 or PARN mutation than in controls (p=2.87×10 -2 ).Our results support the contribution of FPF-linked genes to RA-ILD susceptibility. Copyright ©ERS 2017.
Rojas-Serrano, Jorge; Herrera-Bringas, Denisse; Pérez-Román, Diana I; Pérez-Dorame, Renzo; Mateos-Toledo, Heidegger; Mejía, Mayra
2017-07-01
Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02-0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003-1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.
Interstitial pneumonitis and the risk of chronic allograft rejection in lung transplant recipients.
Mihalek, Andrew D; Rosas, Ivan O; Padera, Robert F; Fuhlbrigge, Anne L; Hunninghake, Gary M; DeMeo, Dawn L; Camp, Phillip C; Goldberg, Hilary J
2013-05-01
The presence of interstitial pneumonitis (IP) on surveillance lung biopsy specimens in lung transplant recipients is poorly described, and its impact on posttransplant outcomes is not established. The following study assessed the association of posttransplant IP with the development of bronchiolitis obliterans syndrome (BOS). We examined all recipients of primary cadaveric lung transplants at our institution between January 1, 2000, and December 31, 2007 (N = 145). Patients had bronchoscopies with BAL, and transbronchial biopsies performed for surveillance during posttransplant months 1, 3, 6, and 12 as well as when clinically indicated. Patients were given a diagnosis of IP if, in the absence of active infection and organizing pneumonia, they showed evidence of interstitial inflammation and fibrosis on two or more biopsy specimens. IP was a significant predictor of BOS (OR, 7.84; 95% CI, 2.84-21.67; P < .0001) and was significantly associated with time to development of BOS (hazard ratio, 3.8; 95% CI, 1.93-7.39; P = .0001) within the first 6 years posttransplant. The presence of IP did not correlate with a significantly higher risk of mortality or time to death. There was no association between the presence of IP and the development of or time to acute rejection. The presence of IP on lung transplant biopsy specimens suggests an increased risk for BOS, which is independent of the presence of acute cellular rejection.
Personalized medicine in interstitial lung diseases.
Spagnolo, Paolo; Oldham, Justin M; Jones, Mark G; Lee, Joyce S
2017-05-01
A number of recent studies have explored the possibility to apply personalized medicine to interstitial lung diseases (ILDs), particularly idiopathic pulmonary fibrosis (IPF), the most common and deadly of the idiopathic interstitial pneumonias. In our review, we summarize and discuss the most recent literature on personalized medicine in IPF as well as hypersensitivity pneumonitis and sarcoidosis, with emphasis on patient subgroups for which a personalized approach to disease prognostication and management may become a reality in the near future. Most of the studies that have explored the applicability of personalized medicine to ILDs have been conducted in patients with IPF. Such studies have suggested the existence of several distinct disease subgroups defined by similar genetic profiles, molecular pathways, exposures and individual lifestyles. Personalized medicine in hypersensitivity pneumonitis is in its infancy. The development and applicability of personalized medicine to sarcoidosis, on the other hand, remains problematic for several reasons, including the lack of a diagnostic gold standard, the highly variable and unpredictable disease course, particularly across patients of different ethnicities, the poor correlation between disease activity and disease severity and the lack of a validated management algorithm. A number of distinct patient subgroups have been identified in ILDs. Although available data need to be validated longitudinally, the possibility to study homogeneous groups of patients may allow prediction of disease behavior and response to treatment with dramatic clinical implications.
Ungprasert, Patompong; Wilton, Katelynn M; Ernste, Floranne C; Kalra, Sanjay; Crowson, Cynthia S; Rajagopalan, Srinivasan; Bartholmai, Brian J
2017-10-01
To evaluate the correlation between measurements from quantitative thoracic high-resolution CT (HRCT) analysis with "Computer-Aided Lung Informatics for Pathology Evaluation and Rating" (CALIPER) software and measurements from pulmonary function tests (PFTs) in patients with idiopathic inflammatory myopathies (IIM)-associated interstitial lung disease (ILD). A cohort of patients with IIM-associated ILD seen at Mayo Clinic was identified from medical record review. Retrospective analysis of HRCT data and PFTs at baseline and 1 year was performed. The abnormalities in HRCT were quantified using CALIPER software. A total of 110 patients were identified. At baseline, total interstitial abnormalities as measured by CALIPER, both by absolute volume and by percentage of total lung volume, had a significant negative correlation with diffusing capacity for carbon monoxide (DLCO), total lung capacity (TLC), and oxygen saturation. Analysis by subtype of interstitial abnormality revealed significant negative correlations between ground glass opacities (GGO) and reticular density (RD) with DLCO and TLC. At one year, changes of total interstitial abnormalities compared with baseline had a significant negative correlation with changes of TLC and oxygen saturation. A negative correlation between changes of total interstitial abnormalities and DLCO was also observed, but it was not statistically significant. Analysis by subtype of interstitial abnormality revealed negative correlations between changes of GGO and RD and changes of DLCO, TLC, and oxygen saturation, but most of the correlations did not achieve statistical significance. CALIPER measurements correlate well with functional measurements in patients with IIM-associated ILD.
UO(2) Oxidative Corrosion by Nonclassical Diffusion.
Stubbs, Joanne E; Chaka, Anne M; Ilton, Eugene S; Biwer, Craig A; Engelhard, Mark H; Bargar, John R; Eng, Peter J
2015-06-19
Using x-ray scattering, spectroscopy, and density-functional theory, we determine the structure of the oxidation front when a UO(2) (111) surface is exposed to oxygen at ambient conditions. In contrast to classical diffusion and previously reported bulk UO(2+x) structures, we find oxygen interstitials order into a nanoscale superlattice with three-layer periodicity and uranium in three oxidation states: IV, V, and VI. This oscillatory diffusion profile is driven by the nature of the electron transfer process, and has implications for understanding the initial stages of oxidative corrosion in materials at the atomistic level.
Yaguchi, Daizo; Ichikawa, Motoshi; Shizu, Masato; Inoue, Noriko; Kobayashi, Daisuke; Imai, Naoyuki; Ito, Masao
2018-05-01
Sometimes, pleural effusion accompanying an acute Mycoplasma pneumoniae infection or tuberculous pleurisy has similar analysis results. We report a case of tuberculous pleurisy which was initially diagnosed as acute M pneumoniae infection, which is of special interest because anti-Mycoplasma antibody results were positive, which served as a red herring. A 20-year-old woman visited the outpatient emergency romm of our hospital for chief complaints of high fever, dry cough, and pleuralgia persiting for 2 days. Since anti-mycoplasma antibody test results were positive, we treated acute M pneumoniae infection and drained her pleural effusion. The condition tended to improve, but on day 16 postadmission, the acid-fast bacterial culture of the pleural effusion was positive for Mycobacterium tuberculosis. Tuberculous pleurisy. After the diagnosis, the patient received antituberculous drugs. She completed treatment with no noticeable adverse events, and the right pleural effusion disappered and diffuse right pleural thickening improved. Exudative pleural effusion with lymphocyte dominance and a high adenosine deaminase level in M pneumoniae infection have been reported. Even though the condition suggests acute M pneumoniae infection, clinicians should be aware that tuberculous pleurisy and M pneumoniae infection can share similar clinical features, and should understand the usefulness and limitations of the anit-Mycoplasma antibody test.
Neumann, E J; Dobbinson, S S A; Welch, E B M; Morris, R S
2007-12-01
Investigations were conducted to determine the cause of an acute, multi-farm outbreak of porcine respiratory disease that included diarrhoea and subsequent loss of body condition in affected pigs. A definition for post-weaning multisystemic wasting syndrome (PMWS) including both clinical and pathological features, previously developed for the pig industry in New Zealand, was applied to the current outbreak. In addition to self-reporting by owners of affected farms, local veterinarians, disease and epidemiology consultants, and animal health officials from the Ministry of Agriculture and Forestry (MAF) were involved in conducting farm visits and submission of diagnostic specimens. Pathogens known to be endemic in the pig industry in New Zealand as well as likely exotic diseases were excluded as causative agents of the outbreak. Clinical signs including dyspnoea, diarrhoea, and rapid loss of body condition were consistent with the New Zealand case definition for PMWS. Interstitial pneumonia, pulmonary oedema, generalised lymph-node enlargement, and presence of porcine circovirus type 2 (PCV2) inclusion bodies were consistently identified in affected pigs. Classical swine fever virus (CSFv), Porcine reproductive and respiratory syndrome virus (PRRSv), and Influenza virus were ruled out, using molecular and traditional virological techniques. Spread of the disease between farms was hypothesised to be facilitated by locally migrating flocks of black-backed seagulls. The original source of the disease incursion was not identified. Based on the consistent presence of circovirus-associated lesions in lymphoid tissues in combination with generalised enlargement of lymph nodes, histiocytic interstitial pneumonia, clinical wasting, and poor response to antibiotic therapy, a diagnosis of PMWS was made. PMWS should be considered in the differential diagnoses of sudden onset of respiratory dyspnoea, diarrhoea, and rapid loss of body condition in young pigs in New Zealand pig herds.
Parra, Edwin Roger; Lin, Flavia; Martins, Vanessa; Rangel, Maristela Peres; Capelozzi, Vera Luiza
2013-01-01
OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. PMID:24473763
Grgic, Aleksandar; Lausberg, Henning; Heinrich, Marc; Koenig, Jochem; Uder, Michael; Sybrecht, Gerhard W; Wilkens, Heinrike
2008-01-01
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. This retrospective observational study included 13 patients (24-64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0-5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0-5 for each lobe]. A comparison of serial changes (interval: 12-96 months posttransplant, 2-4 HRCT examinations/patient) was performed with the sign test. Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 +/- 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 +/- 0.26/year; p = 0.5). A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF. Copyright 2007 S. Karger AG, Basel.
Pulmonary fibrosis and exposure to steel welding fume.
Cosgrove, M P
2015-12-01
Arc welders who have been exposed to high concentrations of steel welding fume for prolonged periods of time may develop pulmonary fibrosis but the nature of the fibrotic changes has been debated over the last 80 years without any clear international consensus. To characterize the nature of the pulmonary fibrosis that develops in response to steel welding fume exposure and to provide a working hypothesis that would explain the findings of the existing research, to provide a platform for future research and to inform future occupational and clinical management of welders with pulmonary effects from welding fume. Review of the world literature on pulmonary fibrosis and welding of steel in all languages using PubMed, with further secondary search of references in the articles found in the primary search. Google and Reference Manager were used as further confirmatory search tools. Only case series and case reports were found but these provided consistent evidence that the consequence of exposure to steel welding fume at high levels for a prolonged period of time is a type of pulmonary fibrosis similar to, and possibly the same as, respiratory bronchiolitis which eventually develops into desquamative interstitial pneumonia with ongoing exposure. Steel welding fume may cause an occupational respiratory bronchiolitis which may develop into de squamative interstitial pneumonia with ongoing exposure. This concept may explain the difficulties in interpreting the wider literature on welding fume and lung function at lower exposures and may also explain the increased risk of lung cancer in welders. © The Author 2015. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Lee, Geewon; Kim, Ki Uk; Lee, Ji Won; Suh, Young Ju; Jeong, Yeon Joo
2017-05-01
Background Although fibrotic idiopathic interstitial pneumonias (IIPs) alone and those combined with pulmonary emphysema are naturally progressive diseases, the process of deterioration and outcomes are variable. Purpose To evaluate and compare serial changes of computed tomography (CT) abnormalities and prognostic predictive factors in fibrotic IIPs alone and those combined with pulmonary emphysema. Material and Methods A total of 148 patients with fibrotic IIPs alone (82 patients) and those combined with pulmonary emphysema (66 patients) were enrolled. Semi-quantitative CT analysis was used to assess the extents of CT characteristics which were evaluated on initial and follow-up CT images. Univariate and multivariate analyses were performed to assess the effects of clinical and CT variables on survival. Results Significant differences were noted between fibrotic scores, as determined using initial CT scans, in the fibrotic IIPs alone (21.22 ± 9.83) and those combined with pulmonary emphysema groups (14.70 ± 7.28) ( P < 0.001). At follow-up CT scans, changes in the extent of ground glass opacities (GGO) were greater ( P = 0.031) and lung cancer was more prevalent ( P = 0.001) in the fibrotic IIPs combined with pulmonary emphysema group. Multivariate Cox proportional hazards analysis showed changes in the extent of GGO (hazard ratio, 1.056) and the presence of lung cancer (hazard ratio, 4.631) were predictive factors of poor survivals. Conclusion Although patients with fibrotic IIPs alone and those combined with pulmonary emphysema have similar mortalities, lung cancer was more prevalent in patients with fibrotic IIPs combined with pulmonary emphysema. Furthermore, changes in the extent of GGO and the presence of lung cancer were independent prognostic factors of poor survivals.
Comorbid Conditions in Idiopathic Pulmonary Fibrosis: Recognition and Management
Oldham, Justin M.; Collard, Harold R.
2017-01-01
Idiopathic pulmonary fibrosis (IPF), a fibrosing interstitial pneumonia of unknown etiology, primarily affects older adults and leads to a progressive decline in lung function and quality of life. With a median survival of 3–5 years, IPF is the most common and deadly of the idiopathic interstitial pneumonias. Despite the poor survivorship, there exists substantial variation in disease progression, making accurate prognostication difficult. Lung transplantation remains the sole curative intervention in IPF, but two anti-fibrotic therapies were recently shown to slow pulmonary function decline and are now approved for the treatment of IPF in many countries around the world. While the approval of these therapies represents an important first step in combatting of this devastating disease, a comprehensive approach to diagnosing and treating patients with IPF remains critically important. Included in this comprehensive assessment is the recognition and appropriate management of comorbid conditions. Though IPF is characterized by single organ involvement, many comorbid conditions occur within other organ systems. Common cardiovascular processes include coronary artery disease and pulmonary hypertension (PH), while gastroesophageal reflux and hiatal hernia are the most commonly encountered gastrointestinal disorders. Hematologic abnormalities appear to place patients with IPF at increased risk of venous thromboembolism, while diabetes mellitus (DM) and hypothyroidism are prevalent metabolic disorders. Several pulmonary comorbidities have also been linked to IPF, and include emphysema, lung cancer, and obstructive sleep apnea. While the treatment of some comorbid conditions, such as CAD, DM, and hypothyroidism is recommended irrespective of IPF, the benefit of treating others, such as gastroesophageal reflux and PH, remains unclear. In this review, we highlight common comorbid conditions encountered in IPF, discuss disease-specific diagnostic modalities, and review the current state of treatment data for several key comorbidities. PMID:28824912
Sand, Jannie M B; Tanino, Yoshinori; Karsdal, Morten A; Nikaido, Takefumi; Misa, Kenichi; Sato, Yuki; Togawa, Ryuichi; Wang, Xintao; Leeming, Diana J; Munakata, Mitsuru
2018-05-04
Idiopathic interstitial pneumonia (IIP) is characterized by an increased rate of extracellular matrix (ECM) remodeling resulting in fibrosis. Acute exacerbations of IIP represent periods of increased disease activity, thus we hypothesized that ECM remodeling was altered during acute exacerbations and investigated this by serological neo-epitope biomarkers. Patients who were sequentially admitted to the hospital with acute exacerbations of IIP were retrospectively analyzed for ECM remodeling at time of exacerbation (AE-IIP) and at clinical stability (S-IIP). Biomarkers released by matrix metalloproteinase-mediated degradation of collagen type I (C1M), III (C3M), IV (C4M), and VI (C6M), elastin (ELM7), versican (VCANM), biglycan (BGM), and C-reactive protein (CRPM) were assessed in serum by competitive ELISAs utilizing neo-epitope specific monoclonal antibodies. Sixty-eight patients at AE-IIP and 29 at S-IIP were included in this retrospective analysis. Of these, 28 and 11 patients, respectively, had idiopathic pulmonary fibrosis. At AE-IIP, serum levels of C4M (p = 0.002) and C6M (p = 0.024) were increased as compared with S-IIP, while ELM7 (p = 0.024) and VCANM (p < 0.0001) were decreased. Lower VCANM levels at AE-IIP were associated with increased risk of mortality (HR 0.64 [95% CI 0.43-0.94], p = 0.022). The ECM remodeling profile was significantly altered during acute exacerbations of IIP, and a biomarker of versican degradation was related to mortality outcome. These results indicate that biomarkers of ECM remodeling may be useful in the non-invasive evaluation of acute exacerbations of IIP. Especially versican degradation, as measured serologically by VCANM, may have prognostic potential and help guide treatment for acute exacerbations.
Lung Ultrasonography to Diagnose Transient Tachypnea of the Newborn.
Liu, Jing; Chen, Xin-Xin; Li, Xiang-Wen; Chen, Shui-Wen; Wang, Yan; Fu, Wei
2016-05-01
This study explored the sensitivity and specificity of ultrasound for diagnosing transient tachypnea of the newborn (TTN). Ultrasound was performed by one export. Patients were placed in a supine, lateral recumbent, or prone position. The probe was placed perpendicular or parallel to the ribs, and each region of the lung was scanned. The scan results were compared with conventional chest radiographic results. A total of 1,358 infants were included in this study. We identified 412 cases without pulmonary diseases, 228 TTN cases, 358 respiratory distress syndrome (RDS) cases, 85 meconium aspiration syndrome (MAS) cases, 215 infectious pneumonia cases, and 60 other cases. The primary ultrasonic characteristic of TTN was pulmonary edema. "White lung" or a "compact B-line" were only observed in severe cases, whereas TTN primarily presented as pulmonary interstitial syndrome or "double lung point." Furthermore, double lung point could appear during the recovery period of severe TTN or RDS, MAS, and pneumonia. Lung consolidation with air bronchograms was not observed in TTN patients. The results showed that white lung or a compact B-line exhibited a sensitivity of 33.8% and a specificity of 91.3% in diagnosing TTN, whereas double lung point exhibited a sensitivity of 45.6% and a specificity of 94.8% in diagnosing severe TTN. Pulmonary edema, alveolar-interstitial syndrome, double lung point, white lung, and compact B-line are the primary ultrasound characteristics of TTN. Ultrasonic diagnosis of TTN based on these findings is accurate and reliable. TTN can be ruled out in the presence of lung consolidation with air bronchograms. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.
Pham, Ngot Thi; Lee, Seul Lee; Park, Suhyun; Lee, Yong Wook; Kang, Hyun Wook
2017-04-01
High-sensitivity temperature sensors have been used to validate real-time thermal responses in tissue during photothermal treatment. The objective of the current study was to evaluate the feasible application of a fiber Bragg grating (FBG) sensor for diffuser-assisted laser-induced interstitial thermotherapy (LITT) particularly to treat tubular tissue disease. A 600 - ? m core-diameter diffuser was employed to deliver 980-nm laser light for coagulation treatment. Both a thermocouple and a FBG were comparatively tested to evaluate temperature measurements in ex vivo liver tissue. The degree of tissue denaturation was estimated as a function of irradiation times and quantitatively compared with light distribution as well as temperature development. At the closer distance to a heat source, the thermocouple measured up to 41% higher maximum temperature than the FBG sensor did after 120-s irradiation (i.e., 98.7 ° C ± 6.1 ° C for FBG versus 131.0 ° C ± 5.1 ° C for thermocouple; p < 0.001 ). Ex vivo porcine urethra tests confirmed the real-time temperature measurements of the FBG sensor as well as consistently circumferential tissue denaturation after 72-s irradiation ( coagulation thickness = 2.2 ± 0.3 ?? mm ). The implementation of FBG can be a feasible sensing technique to instantaneously monitor the temperature developments during diffuser-assisted LITT for treatment of tubular tissue structure.
Mok, Wilson; Stylianopoulos, Triantafyllos; Boucher, Yves; Jain, Rakesh K.
2010-01-01
Purpose Although oncolytic viral vectors show promise for the treatment of various cancers, ineffective initial distribution and propagation throughout the tumor mass often limit the therapeutic response. A mathematical model is developed to describe the spread of herpes simplex virus from the initial injection site. Experimental Design The tumor is modeled as a sphere of radius R. The model incorporates reversible binding, interstitial diffusion, viral degradation, and internalization and physiologic parameters. Three species are considered as follows: free interstitial virus, virus bound to cell surfaces, and internalized virus. Results This analysis reveals that both rapid binding and internalization as well as hindered diffusion contain the virus to the initial injection volume, with negligible spread to the surrounding tissue. Unfortunately, increasing the dose to saturate receptors and promote diffusion throughout the tumor is not a viable option: the concentration necessary would likely compromise safety. However, targeted modifications to the virus that decrease the binding affinity have the potential to increase the number of infected cells by 1.5-fold or more. An increase in the effective diffusion coefficient can result in similar gains. Conclusions This analysis suggests criteria by which the potential response of a tumor to oncolytic herpes simplex virus therapy can be assessed. Furthermore, it reveals the potential of modifications to the vector delivery method, physicochemical properties of the virus, and tumor extracellular matrix composition to enhance efficacy. PMID:19318482
Effect of tumor shape, size, and tissue transport properties on drug delivery to solid tumors
2014-01-01
Background The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, drug extravasation from microvessels or to lymphatic vessels. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to investigate the effect of tumor shape and size on drug delivery to solid tumor. Methods The advanced mathematical model used in our previous work is further developed by adding solute transport equation to the governing equations. After applying appropriate boundary and initial conditions on tumor and surrounding tissue geometry, the element-based finite volume method is used for solving governing equations of drug delivery in solid tumor. Also, the effects of size and shape of tumor and some of tissue transport parameters such as effective pressure and hydraulic conductivity on interstitial fluid flow and drug delivery are investigated. Results Sensitivity analysis shows that drug delivery in prolate shape is significantly better than other tumor shapes. Considering size effect, increasing tumor size decreases drug concentration in interstitial fluid. This study shows that dependency of drug concentration in interstitial fluid to osmotic and intravascular pressure is negligible. Conclusions This study shows that among diffusion and convection mechanisms of drug transport, diffusion is dominant in most different tumor shapes and sizes. In tumors in which the convection has considerable effect, the drug concentration is larger than that of other tumors at the same time post injection. PMID:24987457
[Dermatomyositis associated with anti-MDA5 antibodies and pneumocystis pneumonia: Two lethal cases].
Aymonier, M; Abed, S; Boyé, T; Barazzutti, H; Fournier, B; Morand, J-J
2017-04-01
Dermatomyositis associated with anti-MDA-5 autoantibodies is a recently-described clinical entity. Herein we report two lethal cases involving pneumocystis pneumonia. Case n o 1. A 56-year-old male patient developed cutaneous symptoms consistent with dermatomyositis without muscular involvement. Antinuclear antibodies were present and anti-MDA5 auto-antibodies were identified. The scan showed interstitial lung disease without infection. Significant improvement was obtained with corticosteroids. One month later, the patient presented acute respiratory illness (hypoxemia: PaO 2 60mmHg, exacerbation of lung disease evidenced by a scan, and diagnosis of pneumocystis pneumonia on bronchoalveolar lavage). He died despite appropriate antibiotic therapy and immunosuppressant therapy. Case n o 2. The second case concerned a 52-year-old Vietnamese man who developed more atypical cutaneous symptoms of dermatomyositis without muscular involvement. ANAb responses were positive (1/400) and MDA5 was present. The patient was treated with corticosteroids (40mg/d), hydroxychloroquine, and intravenous immunoglobulin. After significant improvement, the patient developed an acute respiratory illness due to superinfection with pneumocystis and he died despite specific treatment and cyclophosphamide bolus. In dermatomyositis, anti-MDA5 antibody screening is essential for the prognosis since the disease carries a risk of complication with severe lung disease. Bronchial fibroscopy with bronchoalveolar lavage should be considered at the time of diagnosis. Our two cases suggest the need for early screening for pneumocystis pneumonia in the event of respiratory distress and possibly for prophylactic treatment at the start of immunosuppressant therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
Li, Zhifang; Chen, Haiyu; Zhou, Feifan; Li, Hui; Chen, Wei R.
2015-01-01
Photothermal therapy is an effective means to induce tumor cell death, since tumor tissue is more sensitive to temperature increases than normal tissue. Biological responses depend on tissue temperature; target tissue temperature needs to be precisely measured and controlled to achieve desired thermal effects. In this work, a unique photoacoustic (PA) sensor is proposed for temperature measurement during interstitial laser phototherapy. A continuous-wave laser light and a pulsed laser light, for photothermal irradiation and photoacoustic temperature measurement, respectively, were delivered to the target tissue through a fiber coupler. During laser irradiation, the PA amplitude was measured. The Grüneisen parameter and the bioheat equation were used to determine the temperature in strategic positions in the target tissue. Our results demonstrate that the interstitial PA amplitude is a linear function of temperature in the range of 22 to 55 °C, as confirmed by thermocouple measurement. Furthermore, by choosing appropriate laser parameters, the maximum temperature surrounding the active diffuse fiber tip in tissue can be controlled in the range of 41 to 55 °C. Thus, this sensor could potentially be used for fast, accurate, and convenient three-dimensional temperature measurement, and for real-time feedback and control of interstitial laser phototherapy in cancer treatment. PMID:25756865
The evaluation of interstitial Cajal cells distribution in non-tumoral colon disorders.
Becheanu, G; Manuc, M; Dumbravă, Mona; Herlea, V; Hortopan, Monica; Costache, Mariana
2008-01-01
Interstitial cells of Cajal (ICC) are pacemakers that generate electric waves recorded from the gut and are important for intestinal motility. The aim of the study was to evaluate the distribution of interstitial cells of Cajal in colon specimens from patients with idiopathic chronic pseudo-obstruction and other non-tumoral colon disorders as compared with samples from normal colon. The distribution pattern of ICC in the normal and pathological human colon was evaluated by immunohistochemistry using antibodies for CD117, CD34, and S-100. In two cases with intestinal chronic idiopathic pseudo-obstruction we found a diffuse or focal reducing number of Cajal cells, the loss of immunoreactivity for CD117 being correlated with loss of immunoreactivity for CD34 marker. Our study revealed that the number of interstitial cells of Cajal also decrease in colonic diverticular disease and Crohn disease (p<0.05), whereas the number of enteric neurones appears to be normal. These findings might explain some of the large bowel motor abnormalities known to occur in these disorders. Interstitial Cajal cells may play an important role in pathogenesis and staining for CD117 on transmural intestinal surgical biopsies could allow a more extensive diagnosis in evaluation of chronic intestinal pseudo-obstruction.
Laserthermia: a new computer-controlled contact Nd: YAG system for interstitial local hyperthermia.
Daikuzono, N; Suzuki, S; Tajiri, H; Tsunekawa, H; Ohyama, M; Joffe, S N
1988-01-01
Contact Nd:YAG laser surgery is assuming a greater importance in endoscopic and open surgery, allowing coagulation, cutting, and vaporization with greater precision and safety. A new contact probe allows a wider angle of irradiation and diffusion of low-power laser energy (less than 5 watts), using the interstitial technique for producing local hyperthermia. Temperature sensors that monitor continuously can be placed directly into the surrounding tissue or tumor. Using a computer program interfaced with the laser and sensors, a controlled and stable temperature (e.g., 42 degrees C) can be produced in a known volume of tissue over a prolonged period of time (e.g., 20-40 min). This new laserthermia system, using a single low-power Nd:YAG laser for interstitial local hyperthermia, may offer many new advantages in the experimental treatment and clinical management of carcinoma. A multiple system is now being developed.
NASA Astrophysics Data System (ADS)
Mølholt, T. E.; Mantovan, R.; Gunnlaugsson, H. P.; Svane, A.; Masenda, H.; Naidoo, D.; Bharuth-Ram, K.; Fanciulli, M.; Gislason, H. P.; Johnston, K.; Langouche, G.; Ólafsson, S.; Sielemann, R.; Weyer, G.
2014-01-01
Isolated 57Fe atoms were studied in MgO single-crystals by emission Mössbauer spectroscopy following implantation of 57Mn decaying to 57Fe. Four Mössbauer spectral components were found corresponding to different Fe lattice positions and/or charge states. Two components represent Fe atoms substituting Mg as Fe2+ and Fe3+, respectively; a third component is due to Fe in a strongly implantation-induced disturbed region. The fourth component, which is the focus of this paper, can be assigned to Fe at an interstitial site. Comparison of its measured isomer shift with ab initio calculations suggests that the interstitial Fe is located on, or close to, the face of the rock-salt MgO structure. To harmonize such an assignment with the measured near-zero quadrupole interaction a local motion process (cage motion) of the Fe has to be stipulated. The relation of such a local motion as a starting point for long range diffusion is discussed.
Simon, N.S.; Kennedy, M.M.; Massoni, C.S.
1985-01-01
Field and laboratory evaluations were made of a simple, inexpensive diffusion-controlled sampler with ports on two sides at each interval which incorporates 0.2-??m polycarbonate membrane to filter samples in situ. Monovalent and divalent ions reached 90% of equilibrium between sampler contents and the external solution within 3 and 6 hours, respectively. Sediment interstitial water chemical gradients to depths of tens of centimeters were obtained within several days after placement. Gradients were consistent with those determined from interstitial water obtained by centrifugation of adjacent sediment. Ten milliliter sample volumes were collected at 1-cm intervals to determine chemical gradients and dissolved oxygen profiles at depth and at the interface between the sediment and water column. The flux of dissolved species, including oxygen, across the sediment-water interface can be assessed more accurately using this sampler than by using data collected from benthic cores. ?? 1985 Dr W. Junk Publishers.
Digesting a Path Forward: The Utility of Collagenase Tumor Treatment for Improved Drug Delivery.
Dolor, Aaron; Szoka, Francis C
2018-06-04
Collagen and hyaluronan are the most abundant components of the extracellular matrix (ECM) and their overexpression in tumors is linked to increased tumor growth and metastasis. These ECM components contribute to a protective tumor microenvironment by supporting a high interstitial fluid pressure and creating a tortuous setting for the convection and diffusion of chemotherapeutic small molecules, antibodies, and nanoparticles in the tumor interstitial space. This review focuses on the research efforts to deplete extracellular collagen with collagenases to normalize the tumor microenvironment. Although collagen synthesis inhibitors are in clinical development, the use of collagenases is contentious and clinically untested in cancer patients. Pretreatment of murine tumors with collagenases increased drug uptake and diffusion 2-10-fold. This modest improvement resulted in decreased tumor growth, but the benefits of collagenase treatment are confounded by risks of toxicity from collagen breakdown in healthy tissues. In this review, we evaluate the published in vitro and in vivo benefits and limitations of collagenase treatment to improve drug delivery.
Kim, Heakyung; Lee, Yung; Weiner, Daniel; Kaye, Robin; Cahill, Anne Marie; Yudkoff, Marc
2006-01-01
We describe 2 children with severe spastic quadriplegic cerebral palsy (CP) who have significant drooling and frequent aspiration pneumonia. They underwent simultaneous botulinum toxin type A (BTX-A) injections to salivary glands for drooling and prevention of aspiration pneumonia along with single-event multilevel chemoneurolysis (SEMLC) with BTX-A and 5% phenol for severe diffuse spasticity. There was significant improvement in drooling, frequency of aspiration pneumonia, and spasticity without adverse effect. BTX-A injections into the salivary glands, in addition to SEMLC, for these 2 children with medically complicated severe spastic quadriplegic CP, were safe and highly successful procedures, which improved their health-related quality of life.
Kang, Seon Mee; Jin, Heung Yong; Lee, Kyung Ae; Park, Ji Hyun; Baek, Hong Sun; Park, Tae Sun
2013-01-01
We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.
Idiopathic pulmonary fibrosis misdiagnosed as sputum-negative pulmonary tuberculosis.
Isah, Muhammad Danasabe; Abbas, Aminu; Abba, Abdullahi A; Umar, Mohammed
2016-01-01
Idiopathic pulmonary fibrosis (IPF), also known as cryptogenic fibrosing alveolitis, is one of a spectrum of idiopathic interstitial pneumonia. IPF is an increasingly common condition which poses many diagnostic and therapeutic challenges leading to misdiagnosis and mismanagement. We presented a 55-year-old male textile trader who was initially managed as sputum-negative pulmonary tuberculosis before histology report. He presented to our clinic with Breathlessness and cough of 3 years and 2.5 years, respectively. He had commenced anti-tuberculosis two months before presentation without significant relief. General Physical examination and vital signs were essentially normal. SPO2 was 96% on room air. Chest Examination revealed end-inspiratory bi-basal velcro-like crackles. Other systemic examinations were normal. Radiological examination by way of chest X- ray and chest CT showed features suggestive of IPF. The patient also had open Lung biopsy for histology and spirometry which demonstrated restrictive ventilatory function pattern. A diagnosis of Interstitial lung disease probably Idiopathic Pulmonary Fibrosis was entertained. He was commenced on Tab prednisolone, Tab Rabeprazole, with minimal improvement. IPF have often been misdiagnosed and treated as pulmonary tuberculosis with unfavorable outcome.
Lesions of neonatally induced toxoplasmosis in cats.
Dubey, J P; Mattix, M E; Lipscomb, T P
1996-05-01
Five pregnant queens were inoculated orally with Toxoplasma gondii tissue cysts. Twenty-two live and three dead kittens were born 16 to 31 days after inoculation. Four kittens were eaten by queens and, thus, were not available for histologic examination. Twenty-one kittens that died or were euthanatized on day 2 (two kittens), 4 (one kitten), 5 (five kittens), 6 (five kittens), 7 (one kitten), 8 (four kittens), 16 (two kittens), and 29 (one kitten) after birth were studied histologically. T gondii was detected by bioassay and was seen in histologic sections of tissues from all 21 kittens. The histologic lesions associated with neonatal toxoplasmosis were widely disseminated infiltrates of macrophages and neutrophils often accompanied by necrosis; lymphocytes and plasma cells were occasionally present. The most consistent lesions were proliferative interstitial pneumonia (21/21); necrotizing hepatitis (20/21); myocarditis (21/21); skeletal myositis (21/21); glossal myositis (19/19); nonsuppurative encephalitis affecting the cerebrum (18/18), brain stem (15/15), and spinal cord (9/9); uveitis (19/19); necrotizing adrenal adenitis (18/18); and interstitial nephritis (16/21). Placental lesions (2/2) consisted of grossly visible areas of necrosis and mineralization.
Geith, Tobias; Biffar, Andreas; Schmidt, Gerwin; Sourbron, Steven; Dietrich, Olaf; Reiser, Maximilian; Baur-Melnyk, Andrea
2015-01-01
To test the hypothesis that apparent diffusion coefficient (ADC) in vertebral bone marrow of benign and malignant fractures is related to the volume of the interstitial space, determined with dynamic contrast-enhanced (DCE) magnetic resonance imaging. Patients with acute benign (n = 24) and malignant (n = 19) vertebral body fractures were examined at 1.5 T. A diffusion-weighted single-shot turbo-spin-echo sequence (b = 100 to 600 s/mm) and DCE turbo-FLASH sequence were evaluated. Regions of interest were manually selected for each fracture. Apparent diffusion coefficient was determined with a monoexponential decay model. The DCE magnetic resonance imaging concentration-time curves were analyzed using a 2-compartment tracer-kinetic model. Apparent diffusion coefficient showed a significant positive correlation with interstitial volume in the whole study population (Pearson r = 0.66, P < 0.001), as well as in the malignant (Pearson r = 0.64, P = 0.004) and benign (Pearson r = 0.52, P = 0.01) subgroup. A significant correlation between ADC and the permeability-surface area product could be observed when analyzing the whole study population (Spearman rs = 0.40, P = 0.008), but not when separately examining the subgroups. Plasma flow showed a significant correlation with ADC in benign fractures (Pearson r = 0.23, P = 0.03). Plasma volume did not show significant correlations with ADC. The results support the hypothesis that the ADC of a lesion is inversely correlated to its cellularity. This explains previous observations that ADC is reduced in more malignant lesions.
Effects of cation contaminants in conductive TiO2 ceramics
NASA Astrophysics Data System (ADS)
Yan, M. F.; Rhodes, W. W.
1982-12-01
Ten cation contaminants, namely Al, Ga, Co, Fe, Mg, Zn, Zr, Ca, Sr, and Ba were investigated for their effects on the electrical properties, microstructures, and discoloration of conductive TiO2 ceramics. It was found that Al, Ga, Co, Fe, and Mg cause discoloration and increase the electrical resistivity by a factor of 104 to 106 in Nb-doped TiO2 ceramics. The other dopants do not introduce such changes in TiO2. The electrical properties, microstructures, and discoloration were measured in specimens of AlxNb0.007Ti0.993-xO2 with 0≤x≤0.01. When the Al content exceeds a critical value, ranging from 0.48% at 1400 °C to 0.25% at 1200 °C, the electrical resistivities and grain size increase rapidly, and the specimen is discolored from the original black to an ivory white color. Color boundary migration induced by Al diffusion in Nb-doped TiO2 was quantitatively measured. From the kinetics of the boundary migration, the Al diffusivity (D) was calculated to be D=2.67 exp(-53.3 kcal/mole/RT) cm2/s in the temperature range of 1200 to 1400 °C. The rapid diffusion of the small cations, namely Al, Ga, Co, Fe, and Mg, results from an interstitial diffusion mechanism. However, other cations, having a radius larger than the interstitial channel (˜0.77 Å radius), cannot diffuse by this mechanism. Defect reactions are proposed to explain the increase in the electrical resistivity and microstructural changes due to Al diffusion. These defect reactions also show that the problem of acceptor contamination cannot be avoided by adding an excess quantity of donor dopant if the solubility of the donor is much less than that of the acceptor contaminant.
Molecular dynamics simulations of substitutional diffusion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhou, Xiaowang; Jones, Reese E.; Gruber, Jacob
2016-12-18
In atomistic simulations, diffusion energy barriers are usually calculated for each atomic jump path using a nudged elastic band method. Practical materials often involve thousands of distinct atomic jump paths that are not known a priori. Hence, it is often preferred to determine an overall diffusion energy barrier and an overall pre-exponential factor from the Arrhenius equation constructed through molecular dynamics simulations of mean square displacement of the diffusion species at different temperatures. This approach has been well established for interstitial diffusion, but not for substitutional diffusion at the same confidence. Using In 0.1 Ga 0.9 N as an example,more » we have identified conditions where molecular dynamics simulations can be used to calculate highly converged Arrhenius plots for substitutional alloys. As a result, this may enable many complex diffusion problems to be easily and reliably studied in the future using molecular dynamics, provided that moderate computing resources are available.« less
Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi
2016-01-01
This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
The in-vitro antimicrobial activities of some medicinal plants from Cameroon.
Gangoué-Piéboji, J; Pegnyemb, D E; Niyitegeka, D; Nsangou, A; Eze, N; Minyem, C; Mbing, J Ngo; Ngassam, P; Tih, R Ghogomu; Sodengam, B L; Bodo, B
2006-04-01
The antimicrobial activities of 10 plant species (Voacanga africana, Crepis cameroonica, Plagiostyles africana, Crotalaria retusa, Mammea africana, Lophira lanceolata, Ochna afzelii, Ouratea elongata, Ou. flava and Ou. sulcata), each of which is currently used in the traditional medicine of Cameroon, were investigated in vitro. The activities of a methanol extract of each plant were tested, in disc-diffusion assays, against 37 reference or laboratory strains of seven species of microorganism (Staphylococcus aureus, S. epidermidis, Enterococcus hirae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Candida albicans). The minimal inhibitory concentrations of each extract were then estimated, against each of the more susceptible microorganisms (i.e. those giving an inhibition zone measuring at least 9 mm in diameter in the disc-diffusion assays), by agar dilution. Although, in the disc-diffusion assays, each of the 10 methanol extracts investigated displayed some degree of antimicrobial activity against at least one species of microorganism, no activity against the Gram-negative bacteria (Es. coli, K. pneumoniae and Ps. aeruginosa) was observed. The extract with the greatest antimicrobial activity was that of Pl. africana (Euphorbiaceae).
Cortexin diffusion in human eye sclera
DOE Office of Scientific and Technical Information (OSTI.GOV)
Genina, Elina A; Bashkatov, A N; Tuchin, Valerii V
2011-05-31
Investigation of the diffusion of cytamines, a typical representative of which is cortexin, is important for evaluating the drug dose, necessary to provide sufficient concentration of the preparation in the inner tissues of the eye. In the present paper, the cortexin diffusion rate in the eye sclera is measured using the methods of optical coherence tomography (OCT) and reflectance spectroscopy. The technique for determining the diffusion coefficient is based on the registration of temporal dependence of the eye sclera scattering parameters caused by partial replacement of interstitial fluid with the aqueous cortexin solution, which reduces the level of the OCTmore » signal and decreases the reflectance of the sclera. The values of the cortexin diffusion coefficient obtained using two independent optical methods are in good agreement. (optical technologies in biophysics and medicine)« less
“Conjugate Channeling” Effect in Dislocation Core Diffusion: Carbon Transport in Dislocated BCC Iron
Ishii, Akio; Li, Ju; Ogata, Shigenobu
2013-01-01
Dislocation pipe diffusion seems to be a well-established phenomenon. Here we demonstrate an unexpected effect, that the migration of interstitials such as carbon in iron may be accelerated not in the dislocation line direction , but in a conjugate diffusion direction. This accelerated random walk arises from a simple crystallographic channeling effect. is a function of the Burgers vector b, but not , thus a dislocation loop possesses the same everywhere. Using molecular dynamics and accelerated dynamics simulations, we further show that such dislocation-core-coupled carbon diffusion in iron has temperature-dependent activation enthalpy like a fragile glass. The 71° mixed dislocation is the only case in which we see straightforward pipe diffusion that does not depend on dislocation mobility. PMID:23593255
Ishii, Akio; Li, Ju; Ogata, Shigenobu
2013-01-01
Dislocation pipe diffusion seems to be a well-established phenomenon. Here we demonstrate an unexpected effect, that the migration of interstitials such as carbon in iron may be accelerated not in the dislocation line direction ξ, but in a conjugate diffusion direction. This accelerated random walk arises from a simple crystallographic channeling effect. c is a function of the Burgers vector b, but not ξ, thus a dislocation loop possesses the same everywhere. Using molecular dynamics and accelerated dynamics simulations, we further show that such dislocation-core-coupled carbon diffusion in iron has temperature-dependent activation enthalpy like a fragile glass. The 71° mixed dislocation is the only case in which we see straightforward pipe diffusion that does not depend on dislocation mobility.
NASA Astrophysics Data System (ADS)
Mang, Thomas S.; Nava, Hector R.; Regal, Anne-Marie
1989-06-01
Clinical studies in photodynamic therapy (PDT) have utilized lasers to take advantage of coupling efficiencies to optical fibers allowing light to be delivered to many areas of the body. This is particularly true in endoscopic PDT. Both interstitial and superficial delivery techniques can be applied using one of a variety of delivery fibers available. A fiber with an optically flat end with a lens to produce a spot with a homogeneous intensity is used for superficial applications. Diffusers of various lengths, at the tip of a fiber, produce a cylindrical isotropic pattern and are suited for either intraluminal or interstitial illuminations.
Gallium uptake in tryptophan-related pulmonary disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, S.M.; Park, C.H.; Intenzo, C.M.
1991-02-01
We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking high doses of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations.
Septicemia in a neonatal calf associated with Chromobacterium violaceum.
Ajithdoss, D K; Porter, B F; Calise, D V; Libal, M C; Edwards, J F
2009-01-01
Chromobacterium violaceum infections are highly fatal and rarely reported in domestic animals. This report describes a fatal case of C. violaceum septicemia in a 7-day-old female beef calf. The calf had necrosuppurative omphalophlebitis, necrotizing interstitial pneumonia, necrosuppurative hepatitis and splenitis, anterior uveitis with hypopyon, suppurative polyarthritis, and disseminated hemorrhagic meningitis with multifocal necrotizing encephalitis. Histologically, clusters of gram-negative bacilli were found in many of the lesions. C. violaceum was isolated in high numbers from the lungs, liver, spleen, carpus, and in pure culture from the cerebrospinal fluid. To our knowledge, this is the first case report of chromobacteriosis in a calf.
Infection prevention for patients with acute leukemia using laminar air flow rooms.
Masaoka, T
1986-01-01
Infection prevention using laminar air flow (LAF) rooms was studied. For the effective and economical usage of LAF rooms, our trials with ozone decontamination were deemed very convenient and effective. In maintaining LAF clean, insects were found to be a critical factor regarding fungus contamination of LAF. As to its efficacy of infection prevention, LAF decreased infection during remission induction from 113/100 to 28/100. The infections reduced by LAF were pneumonia, upper respiratory infection and skin abscess, while sepsis and perianal infection were not affected. Treatment in LAF rooms also seemed to have comparable influence on interstitial pneumonitis after bone marrow transplantation.
Clinical and pathologic changes in a guinea pig aerosol challenge model of acute Q fever.
Russell-Lodrigue, K E; Zhang, G Q; McMurray, D N; Samuel, J E
2006-11-01
Acute Q fever is a zoonotic disease caused by the obligate intracellular bacterium Coxiella burnetii and can manifest as a flu-like illness, pneumonia, or hepatitis. A need exists in Q fever research for animal models mimicking both the typical route of infection (inhalation) and the clinical illness seen in human cases of Q fever. A guinea pig aerosol challenge model was developed using C. burnetii Nine Mile phase I (RSA 493), administered using a specialized chamber designed to deliver droplet nuclei directly to the alveolar spaces. Guinea pigs were given 10(1) to 10(6) organisms and evaluated for 28 days postinfection. Clinical signs included fever, weight loss, respiratory difficulty, and death, with the degree and duration of response corresponding to the dose of organism delivered. Histopathologic evaluation of the lungs of animals infected with a high dose showed coalescing panleukocytic bronchointerstitial pneumonia at 7 days postinfection that resolved to multifocal lymphohistiocytic interstitial pneumonia by 28 days. Guinea pigs receiving a killed whole-cell vaccine prior to challenge with the highest dose of C. burnetii were protected against lethal infection and did not develop fever. Clinical signs and pathological changes noted for these guinea pigs were comparable to those seen in human acute Q fever, making this an accurate and valuable animal model of human disease.
Mimori, Tsuneyo; Harigai, Masayoshi; Atsumi, Tatsuya; Fujii, Takao; Kuwana, Masataka; Matsuno, Hiroaki; Momohara, Shigeki; Takei, Syuji; Tamura, Naoto; Takasaki, Yoshinari; Ikeuchi, Satoshi; Kushimoto, Satoru; Koike, Takao
2017-09-01
To determine the real-world safety and effectiveness of iguratimod (IGU) for rheumatoid arthritis (RA), a 52-week, Japanese, post-marketing surveillance study was conducted. An interim analysis at week 24 was performed. This study included all RA patients who received IGU following its introduction to the market. All adverse events (AEs) and adverse drug reactions (ADRs) were collected. Effectiveness was evaluated by the change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) from baseline to week 24. Safety was analyzed in 2679 patients. The overall incidences of AEs, ADRs, and serious ADRs were 38.41, 31.65, and 3.21%, respectively; the most commonly reported serious ADRs were pneumonia/bacterial pneumonia, interstitial lung disease, and Pneumocystis jiroveci pneumonia. Concomitant glucocorticoid use and comorbid conditions associated with respiratory disease were identified as risk factors for serious infections. Pulmonary alveolar hemorrhage and increased international normalized ratio of prothrombin time were observed with concomitant use of IGU and warfarin. The DAS28-CRP decreased from baseline to week 24. Although a safety concern was identified with concomitant use of IGU and warfarin, this real-world study showed no other new safety concerns and similar effectiveness to clinical trials. IGU is a new therapeutic option for RA patients.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Xiao-Yong; Lu, Yong; Zhang, Ping, E-mail: zhang-ping@iapcm.ac.cn
2015-04-28
The temperature-dependent diffusion coefficient of interstitial helium in zirconium carbide (ZrC) matrix is calculated based on the transition state theory. The microscopic parameters in the activation energy and prefactor are obtained from first-principles total energy and phonon frequency calculations including the all atoms. The obtained activation energy is 0.78 eV, consistent with experimental value. Besides, we evaluated the influence of C and Zr vacancies as the perturbation on helium diffusion, and found the C vacancy seems to confine the mobility of helium and the Zr vacancy promotes helium diffusion in some extent. These results provide a good reference to understand themore » behavior of helium in ZrC matrix.« less
A novel pulmonary polyomavirus in alpacas (Vicugna pacos).
Dela Cruz, Florante N; Li, Linlin; Delwart, Eric; Pesavento, P A
2017-03-01
Viral metagenomic analysis detected a novel polyomavirus in a 6-month old female alpaca (Vicugna pacos) euthanized after a diagnosis of disseminated lymphosarcoma. The viral genome was fully sequenced, found to be similar to other polyomaviruses in gene architecture and provisionally named Alpaca polyomavirus or AlPyV. Viral nucleic acid was detected by PCR in venous blood, spleen, thymus, and lung. AlPyV phylogenetically clustered in the "Wuki" group of PyVs, which includes WU and KI polyomaviruses, commonly found in human respiratory samples. In an ISH analysis of 17 alpaca necropsies, 7 had detectable virus within the lung. In animals without pneumonia, probe hybridization was restricted to the nuclei of scattered individual bronchiolar epithelial cells. Three of the ISH positive alpacas had interstitial pneumonia of unknown origin, and in these animals there was viral nucleic acid detected in bronchiolar epithelium, type II pneumocytes, and alveolar macrophages. The pattern of AlPyV distribution is consistent with a persistent respiratory virus that has a possible role in respiratory disease. Copyright © 2017 Elsevier B.V. All rights reserved.
Madar, Cristian S; Lewin-Smith, Michael R; Franks, Teri J; Harley, Russell A; Klaric, John S; Morris, Michael J
2017-08-01
The current understanding of associations between lung disease and military deployment to Southwest Asia, including Iraq and Afghanistan, is both controversial and limited. We sought to clarify the relation between military deployment and biopsy-proven lung disease. Retrospective data were analyzed for military personnel with non-neoplastic lung biopsies evaluated at the Armed Forces Institute of Pathology or Joint Pathology Center (January 2005 to December 2012). Of 391 subjects, 137 (35.0%) had deployed to Southwest Asia prior to biopsy. Compared to non-deployed subjects, those deployed were younger (median age 37 vs. 51 years) with higher representation of African Americans (30.0 vs. 16.9%). Deployed patients were more likely diagnosed with non-necrotizing granulomas (OR 2.4). Non-deployed subjects had higher frequency of idiopathic interstitial pneumonias, particularly organizing pneumonia. Prevalence of small airways diseases including constrictive bronchiolitis was low. This study provides a broader understanding of diversity of biopsy-proven non-neoplastic lung disease as it relates to military deployment to Southwest Asia and importantly did not show an increased prevalence of small airway disease to include constrictive bronchiolitis.
Imaging diagnosis--pulmonary metastases in New World camelids.
Gall, David A; Zekas, Lisa J; Van Metre, David; Holt, Timothy
2006-01-01
The radiographic appearance of pulmonary metastatic disease from carcinoma is described in a llama and an alpaca. In one, a diffuse miliary pattern was seen. In the other, a more atypical unstructured interstitial pattern was recognized. Metastatic pulmonary neoplasia in camelids may assume a generalized miliary or unstructured pattern.
Linear feasibility algorithms for treatment planning in interstitial photodynamic therapy
NASA Astrophysics Data System (ADS)
Rendon, A.; Beck, J. C.; Lilge, Lothar
2008-02-01
Interstitial Photodynamic therapy (IPDT) has been under intense investigation in recent years, with multiple clinical trials underway. This effort has demanded the development of optimization strategies that determine the best locations and output powers for light sources (cylindrical or point diffusers) to achieve an optimal light delivery. Furthermore, we have recently introduced cylindrical diffusers with customizable emission profiles, placing additional requirements on the optimization algorithms, particularly in terms of the stability of the inverse problem. Here, we present a general class of linear feasibility algorithms and their properties. Moreover, we compare two particular instances of these algorithms, which are been used in the context of IPDT: the Cimmino algorithm and a weighted gradient descent (WGD) algorithm. The algorithms were compared in terms of their convergence properties, the cost function they minimize in the infeasible case, their ability to regularize the inverse problem, and the resulting optimal light dose distributions. Our results show that the WGD algorithm overall performs slightly better than the Cimmino algorithm and that it converges to a minimizer of a clinically relevant cost function in the infeasible case. Interestingly however, treatment plans resulting from either algorithms were very similar in terms of the resulting fluence maps and dose volume histograms, once the diffuser powers adjusted to achieve equal prostate coverage.
Grain growth and pore coarsening in dense nano-crystalline UO 2+x fuel pellets
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yao, Tiankai; Mo, Kun; Yun, Di
Dense nano-sized UO 2+x pellets are synthesized by spark plasma sintering with controlled stoichiometries (UO 2.03 and UO 2.11) and grain sizes (~100 nm), and subsequently isothermally annealed to study their effects on grain growth kinetics and microstructure stability. The grain growth kinetics is determined and analyzed focusing on the interaction between grain boundary migration, pore growth and coalescence. Grains grow much bigger in nano-sized UO 2.11 than UO 2.03 upon thermal annealing, consistent with the fact that hyper-stoichiometric UO 2+x is beneficial for sintering due to enhanced U ion diffusion from excessive O ion interstitials. The activation energies ofmore » the grain growth for UO 2.03 and UO 2.11 are determined as ~1.0 and 1.3~2.0 eV, respectively. As compared with the micron-sized UO 2 in which volumetric diffusion dominates the grain coarsening with an activation energy of ~3.0 eV, the enhanced grain growth kinetics in nano-sized UO 2+x suggests that grain boundary diffusion controls grain growth. Lastly, the higher activation energy of more hyper-stoichiometric nano-sized UO 2.11 may be attributed to the excessive O interstitials pinning grain boundary migration.« less
Grain growth and pore coarsening in dense nano-crystalline UO 2+x fuel pellets
Yao, Tiankai; Mo, Kun; Yun, Di; ...
2017-03-25
Dense nano-sized UO 2+x pellets are synthesized by spark plasma sintering with controlled stoichiometries (UO 2.03 and UO 2.11) and grain sizes (~100 nm), and subsequently isothermally annealed to study their effects on grain growth kinetics and microstructure stability. The grain growth kinetics is determined and analyzed focusing on the interaction between grain boundary migration, pore growth and coalescence. Grains grow much bigger in nano-sized UO 2.11 than UO 2.03 upon thermal annealing, consistent with the fact that hyper-stoichiometric UO 2+x is beneficial for sintering due to enhanced U ion diffusion from excessive O ion interstitials. The activation energies ofmore » the grain growth for UO 2.03 and UO 2.11 are determined as ~1.0 and 1.3~2.0 eV, respectively. As compared with the micron-sized UO 2 in which volumetric diffusion dominates the grain coarsening with an activation energy of ~3.0 eV, the enhanced grain growth kinetics in nano-sized UO 2+x suggests that grain boundary diffusion controls grain growth. Lastly, the higher activation energy of more hyper-stoichiometric nano-sized UO 2.11 may be attributed to the excessive O interstitials pinning grain boundary migration.« less
NASA Astrophysics Data System (ADS)
Shropshire, Steven Leslie
Point defects in plastically deformed Au, Pt, and Ni were studied with atomic-scale sensitivity using the perturbed gamma-gamma angular correlations (PAC) technique by monitoring formation and transformation of complexes of vacancy defects with very dilute ^{111}In/ ^{111}Cd solute probes. Three topics were investigated: (1) Production of vacancy defects during plastic deformation of Au was investigated to differentiate models of defect production. Concentrations of mono-, di-, and tri-vacancy species were measured in Au, and the ratio of mono- to di-vacancies was found to be independent of the amount of deformation. Results indicate that point defects are produced in correlated lattice locations, such as in "strings", as a consequence of dislocation interactions and not at random locations. (2) Hydrogen interactions with vacancy-solute complexes were studied in Pt. From thermal detrapping experiments, binding of hydrogen in complexes with mono-, di- and tri-vacancies was determined using a model for hydrogen diffusing in a medium with traps, with enthalpies all measured in the narrow range 0.23-0.28 eV, proving that the binding is insensitive to the precise structure of small vacancy clusters. Nuclear relaxation of the probe in a trivacancy complex in Pt was studied as a function of temperature, from which an activation energy of 0.34 eV was measured. This value is inconsistent with relaxation caused by diffusion or trapping of hydrogen, but explainable by dynamical hopping of the PAC probe atom in a cage of vacancies. (3) By observing transformations between vacancy-solute complexes induced by annihilation reactions, it was demonstrated that interstitials are produced during plastic deformation. The evolution of concentrations of the different vacancy complexes under an interstitial flux was measured and analyzed using a kinetic-rate model, from which interstitial capture cross-sections for the different vacancy complexes and the relative quantities of interstitial species in the flux were determined. Deformation of Au was found to produce only mono- and di-interstitial fluxes in a 1:2 ratio. Cross-sections increased rapidly with the number of vacancies, which is attributed to the amount of relaxation of lattice strains around solute-vacancy complexes.
Luo, Qun; Han, Qian; Chen, Xiaobo; Xie, Jiaxing; Wu, Lulu
2013-01-01
Objectives To evaluate the efficacy and safety of lung biopsies by video-assisted thoracoscopy surgery (VATS) in the diagnosis of undefined interstitial lung disease (ILD). Patients and methods The retrospective analysis was performed in 32 who patients underwent VATS for the diagnosed with ILD from Jan 2007 to Dec 2011. The main reason for VATS for all the patients was due to no specific diagnosis could be obtained after non-invasive methods, transbronchial lung biopsy (TBLB) examination and the consultation with pulmonologist, radiologist and pathologist. The clinical profiles, chest high resolution computerized tomography (HRCT), laboratory profile, TBLB as well as the diagnosis of before and after the VATS were analyzed. The surgery site, biopsy number, duration of the thoracic drain, post-operative complications were also recorded. The 30- and 90-day post-operative mortality rates were calculated. The risk factors associated with the incidence of post-operative complications were assessed. Results The specific diagnosis could be established in all patients after VATS lung biopsies, with change from previous ones in 27 (84.4%). Among 20 cases (62.5%) diagnosed as unclassified ILD before the surgery, 14 (70.0%) were diagnosed as nonspecific interstitial pneumonia (NSIP), 3 (15.0%) as idiopathic pulmonary fibrosis (IPF) and 3 (15.0%) as connective tissue disease-related ILD (CTD-ILD). Among the 7 cases with complete change of diagnosis after VATS, 4 (57.1%) were cryptogenic organizing pneumonia (COP). The number of site of biopsy had no significant impact on the diagnostic efficacy. There were no significant change of vital sign and lung function after the VATS. 21 (65.6%) patients had post-operative complications, including pulmonary infection (56.3%), pulmonary atelectasis (28.1%) and pneumothorax (25.0%). The 30- and 90-day mortality rates were 0 and 5.2% respectively. Patients were divided into 2 groups based on the incidence of post-operative complications, and no significant difference was found in regards to the age, body mass index (BMI), smoking index, lung function, anesthesia method, duration of remaining the thoracic drain and the use of immunosuppressive drugs or steroids. Conclusions VATS is a safe and effective procedure for the diagnosis of ILD which were unclassified after routine evaluation, transbronchial lung biopsy and consultation with pulmonologist, radiologist and pathologist. PMID:23825760
Effects of hydration on steric and electric charge-induced interstitial volume exclusion--a model.
Øien, Alf H; Justad, Sigrid R; Tenstad, Olav; Wiig, Helge
2013-09-03
The presence of collagen and charged macromolecules like glycosaminoglycans (GAGs) in the interstitial space limits the space available for plasma proteins and other macromolecules. This phenomenon, known as interstitial exclusion, is of importance for interstitial fluid volume regulation. Physical/mathematical models are presented for calculating the exclusion of electrically charged and neutral macromolecules that equilibrate in the interstitium under various degrees of hydration. Here, a central hypothesis is that the swelling of highly electrically charged GAGs with increased hydration shields parts of the neutral collagen of the interstitial matrix from interacting with electrically charged macromolecules, such that exclusion of charged macromolecules exhibits change due to steric and charge effects. GAGs are also thought to allow relatively small neutral, but also charged macromolecules neutralized by a very high ionic strength, diffuse into the interior of GAGs, whereas larger macromolecules may not. Thus, in the model, relatively small electrically charged macromolecules, such as human serum albumin, and larger neutral macromolecules such as IgG, will have quite similar total volume exclusion properties in the interstitium. Our results are in agreement with ex vivo and in vivo experiments, and suggest that the charge of GAGs or macromolecular drugs may be targeted to increase the tissue uptake of macromolecular therapeutic agents. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Li, Hong; Qin, Yuan; Yang, Yingying; Yao, Man; Wang, Xudong; Xu, Haixuan; Phillpot, Simon R.
2018-03-01
Molecular dynamics method is used and scheme of calculational tests is designed. The atomic evolution view of the interaction between grain boundary (GB) and irradiation-induced point defects is given in six symmetric tilt GB structures of bcc tungsten with the energy of the primary knock-on atom (PKA) EPKA of 3 and 5 keV and the simulated temperature of 300 K. During the collision cascade with GB structure there are synergistic mechanisms to reduce the number of point defects: one is vacancies recombine with interstitials, and another is interstitials diffuse towards the GB with vacancies almost not move. The larger the ratio of the peak defect zone of the cascades overlaps with the GB region, the statistically relative smaller the number of surviving point defects in the grain interior (GI); and when the two almost do not overlap, vacancy-intensive area generally exists nearby GBs, and has a tendency to move toward GB with the increase of EPKA. In contrast, the distribution of interstitials is relatively uniform nearby GBs and is affected by the EPKA far less than the vacancy. The GB has a bias-absorption effect on the interstitials compared with vacancies. It shows that the number of surviving vacancies statistically has increasing trend with the increase of the distance between PKA and GB. While the number of surviving interstitials does not change much, and is less than the number of interstitials in the single crystal at the same conditions. The number of surviving vacancies in the GI is always larger than that of interstitials. The GB local extension after irradiation is observed for which the interstitials absorbed by the GB may be responsible. The designed scheme of calculational tests in the paper is completely applicable to the investigation of the interaction between other types of GBs and irradiation-induced point defects.
Interstitial loop transformations in FeCr
Béland, Laurent Karim; Osetsky, Yuri N.; Stoller, Roger E.; ...
2015-03-27
Here, we improve the Self-Evolving Atomistic Kinetic Monte Carlo (SEAKMC) algorithm by integrating the Activation Relaxation Technique nouveau (ARTn), a powerful open-ended saddle-point search method, into the algorithm. We use it to investigate the reaction of 37-interstitial 1/2[1 1 1] and 1/2[View the MathML source] loops in FeCr at 10 at.% Cr. They transform into 1/2[1 1 1], 1/2[View the MathML source], [1 0 0] and [0 1 0] 74-interstitial clusters with an overall barrier of 0.85 eV. We find that Cr decoration locally inhibits the rotation of crowdions, which dictates the final loop orientation. Moreover, the final loop orientationmore » depends on the details of the Cr decoration. Generally, a region of a given orientation is favored if Cr near its interface with a region of another orientation is able to inhibit reorientation at this interface more than the Cr present at the other interfaces. Also, we find that substitutional Cr atoms can diffuse from energetically unfavorable to energetically favorable sites within the interlocked 37-interstitial loops conformation with barriers of less than 0.35 eV.« less
Magnetic resonance thermometry for monitoring photothermal effects of interstitial laser irradiation
NASA Astrophysics Data System (ADS)
Goddard, Jessica; Jose, Jessnie; Figueroa, Daniel; Le, Kelvin; Liu, Hong; Nordquist, Robert E.; Hode, Tomas; Chen, Wei R.
2012-03-01
Selective photothermal interaction using dye-assisted non-invasive laser irradiation has limitations when treating deeper tumors or when the overlying skin is heavily pigmented. We developed an interstitial laser irradiation method to induce the desired photothermal effects. An 805-nm near-infrared laser with a cylindrical diffuser was used to treat rat mammary tumors by placing the active tip of the fiber inside the target tumors. Three different power settings (1.0 to 1.5 watts) were applied to treat animal tumors with an irradiation duration of 10 minutes. The temperature distributions of the treated tumors were measured by a 7.1-Tesla magnetic resonance imager using proton resonance frequency (PRF) method. Three-dimensional temperature profiles were reconstructed and assessed using PRF. This is the first time a 7.1-Tesla magnetic resonance imager has been used to monitor interstitial laser irradiation via PRF. This study provides a basic understanding of the photothermal interaction needed to control the thermal damage inside tumor using interstitial laser irradiation. It also shows that PRF can be used effectively in monitoring photothermal interaction. Our long-term goal is to develop a PRF-guided laser therapy for cancer treatment.
Modeling and Measurement of Correlation between Blood and Interstitial Glucose Changes
Shi, Ting; Li, Dachao; Li, Guoqing; Zhang, Yiming; Xu, Kexin; Lu, Luo
2016-01-01
One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF. PMID:27239479
Yamamoto, Yuzo; Okamoto, Isamu; Otsubo, Kohei; Iwama, Eiji; Hamada, Naoki; Harada, Taishi; Takayama, Koichi; Nakanishi, Yoichi
2015-10-01
Alectinib, the second generation anaplastic lymphoma kinase (ALK) inhibitor, has significant potency in patients with ALK rearrangement positive non-small cell lung cancer (NSCLC), and its toxicity is generally well tolerable. We report a patient who developed severe acute interstitial lung disease after alectinib treatment. An 86-year-old woman with stage IV lung adenocarcinoma positive for rearrangement of ALK gene was treated with alectinib. On the 215th day after initiation of alectinib administration, she was admitted to our hospital with the symptom of progressive dyspnea. Computed tomography (CT) revealed diffuse ground glass opacities and consolidations in both lungs, and analysis of bronchoalveolar lavage fluid revealed pronounced lymphocytosis. There was no evidence of infection or other specific causes of her condition, and she was therefore diagnosed with interstitial lung disease induced by alectinib. Her CT findings and respiratory condition improved after steroid pulse therapy. As far as we are aware, this is the first reported case of alectinib-induced severe interstitial lung disease (ILD). We should be aware of the possibility of such a severe adverse event and should therefore carefully monitor patients treated with this drug.
Ergün, Recai; Evcik, Ender; Ergün, Dilek; Ergan, Begüm; Özkan, Esin; Gündüz, Özge
2017-05-05
The number of studies where non-malignant pulmonary diseases are evaluated after occupational arsenic exposure is very few. To investigate the effects of occupational arsenic exposure on the lung by high-resolution computed tomography and pulmonary function tests. Retrospective cross-sectional study. In this study, 256 workers with suspected respiratory occupational arsenic exposure were included, with an average age of 32.9±7.8 years and an average of 3.5±2.7 working years. Hair and urinary arsenic levels were analysed. High-resolution computed tomography and pulmonary function tests were done. In workers with occupational arsenic exposure, high-resolution computed tomography showed 18.8% pulmonary involvement. In pulmonary involvement, pulmonary nodule was the most frequently seen lesion (64.5%). The other findings of pulmonary involvement were 18.8% diffuse interstitial lung disease, 12.5% bronchiectasis, and 27.1% bullae-emphysema. The mean age of patients with pulmonary involvement was higher and as they smoked more. The pulmonary involvement was 5.2 times higher in patients with skin lesions because of arsenic. Diffusing capacity of lung for carbon monoxide was significantly lower in patients with pulmonary involvement. Besides lung cancer, chronic occupational inhalation of arsenic exposure may cause non-malignant pulmonary findings such as bronchiectasis, pulmonary nodules and diffuse interstitial lung disease. So, in order to detect pulmonary involvement in the early stages, workers who experience occupational arsenic exposure should be followed by diffusion test and high-resolution computed tomography.
Reversible geminate recombination of hydrogen-bonded water molecule pair
NASA Astrophysics Data System (ADS)
Markovitch, Omer; Agmon, Noam
2008-08-01
The (history independent) autocorrelation function for a hydrogen-bonded water molecule pair, calculated from classical molecular dynamics trajectories of liquid water, exhibits a t-3/2 asymptotic tail. Its whole time dependence agrees quantitatively with the solution for reversible diffusion-influenced geminate recombination derived by Agmon and Weiss [J. Chem. Phys. 91, 6937 (1989)]. Agreement with diffusion theory is independent of the precise definition of the bound state. Given the water self-diffusion constant, this theory enables us to determine the dissociation and bimolecular recombination rate parameters for a water dimer. (The theory is indispensable for obtaining the bimolecular rate coefficient.) Interestingly, the activation energies obtained from the temperature dependence of these rate coefficients are similar, rather than differing by the hydrogen-bond (HB) strength. This suggests that recombination requires displacing another water molecule, which meanwhile occupied the binding site. Because these activation energies are about twice the HB strength, cleavage of two HBs may be required to allow pair separation. The autocorrelation function without the HB angular restriction yields a recombination rate coefficient that is larger than that for rebinding to all four tetrahedral water sites (with angular restrictions), suggesting the additional participation of interstitial sites. Following dissociation, the probability of the pair to be unbound but within the reaction sphere rises more slowly than expected, possibly because binding to the interstitial sites delays pair separation. An extended diffusion model, which includes an additional binding site, can account for this behavior.
Tafen, De Nyago
2015-02-14
The diffusion of dilute hydrogen in fcc Ni–Al and Ni–Fe binary alloys was examined using kinetic Monte Carlo method with input kinetic parameters obtained from first-principles density functional theory. The simulation involves the implementation of computationally efficient energy barrier model that describes the configuration dependence of the hydrogen hopping. The predicted hydrogen diffusion coefficients in Ni and Ni 89.4Fe 10.6 are compared well with the available experimental data. In Ni–Al, the model predicts lower hydrogen diffusivity compared to that in Ni. Overall, diffusion prefactors and the effective activation energies of H in Ni–Fe and Ni–Al are concentration dependent of themore » alloying element. Furthermore, the changes in their values are the results of the short-range order (nearest-neighbor) effect on the interstitial diffusion of hydrogen in fcc Ni-based alloys.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Martinavicius, A.; Abrasonis, G.; Moeller, W.
2011-10-01
The nitrogen diffusivity in single-crystalline AISI 316L austenitic stainless steel (ASS) during ion nitriding has been investigated at different crystal orientations ((001), (110), (111)) under variations of ion flux (0.3-0.7 mA cm{sup -2}), ion energy (0.5-1.2 keV), and temperature (370-430 deg. C). The nitrogen depth profiles obtained from nuclear reaction analysis are in excellent agreement with fits using the model of diffusion under the influence of traps, from which diffusion coefficients were extracted. At fixed ion energy and flux, the diffusivity varies by a factor up to 2.5 at different crystal orientations. At (100) orientation, it increases linearly with increasingmore » ion flux or energy. The findings are discussed on the basis of atomistic mechanisms of interstitial diffusion, potential lattice distortions, local decomposition, and ion-induced lattice vibrational excitations.« less
Aljanaby, Ahmed Abduljabbar Jaloob; Alhasnawi, Haneen Mohammed Reda Jaber
2017-01-01
Burns infections and urinary tract infections are the most important prevalent diseases in Asian countries, such as Iraq. Klebsiella pneumoniae is one of the most important bacteria cause this type of infections especially in hospitals. Therefore, the aim of this study was to investigate the prevalence of multi-drug resistance K. pneumoniae and extended-spectrum beta-lactamases producing K. pneumoniae isolates from inpatients with urinary tract infection and burns infections in Al-Kufa hospital in Al-Najaf province, Iraq. A total of 285 clinical samples were collected from in-patients infected with urinary tract infection (141 urine samples) and burns infections (144 burns swabs). Fourteen different antibiotics were used by disc diffusion method and 13 antimicrobials resistance genes were used by PCR technique. A total of 43 K. pneumoniae strains were isolated. The highest resistance rate was observed for amoxicillin 25 μg and amoxicillin+clavulanic acid 20+10 μg (97.67%) while the lowest resistance rate was observed for imipenem 10 μg (9.30%). The most common resistance associated-genes were blaSHV (86.04%) and at lower prevalence were IMP (9.30%). Klebsiella pneumoniae strains isolated from burns infections were more virulent than those isolated from urinary tract infections.
Hozumi, Hironao; Enomoto, Noriyuki; Kono, Masato; Fujisawa, Tomoyuki; Inui, Naoki; Nakamura, Yutaro; Sumikawa, Hiromitsu; Johkoh, Takeshi; Nakashima, Ran; Imura, Yoshitaka; Mimori, Tsuneyo; Suda, Takafumi
2015-01-01
Background In polymyositis/dermatomyositis (PM/DM), anti-aminoacyl-tRNA synthetase (ARS) antibodies are closely associated with interstitial lung disease (ILD), a frequent pulmonary complication. However, the clinical significance of anti-ARS antibodies is not well established. Objective We aimed to evaluate the clinical significance of anti-ARS antibodies in PM/DM-ILD patients. Methods Forty-eight consecutive PM/DM-ILD patients were studied retrospectively. Anti-ARS antibodies were screened by ELISA and confirmed by RNA immunoprecipitation test. Medical records, high-resolution computed tomography images, and surgical lung biopsy specimens were compared between ARS-positive (ARS group) and ARS-negative patients (non-ARS group). Results Anti-ARS antibodies were detected in 23 of 48 patients (48%). Radiologically, nonspecific interstitial pneumonia (NSIP) pattern was observed more frequently in the ARS group than in the non-ARS group (73.9% vs. 40%, P = 0.02). Pathologically, NSIP was the most frequent in both groups. Ten-year survival rate was also significantly higher in the ARS group than in the non-ARS group (91.6% vs. 58.7%, P = 0.02). Univariate Cox hazards analysis revealed that the presence of anti-ARS antibodies was associated with better prognosis (HR = 0.34, 95% CI 0.08–0.80; P = 0.01). Conclusions The presence of anti-ARS antibodies is a possible prognostic marker in patients with PM/DM-ILD. PMID:25789468
Prabhu, Somnath J.; Crothers, Kristina; Stern, Eric J.; Godwin, J. David; Pipavath, Sudhakar N.
2014-01-01
The human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) pandemic has entered its 4th decade. Since the introduction of combination antiretroviral therapy (ART) in 1996, the number of AIDS-related deaths has plateaued worldwide. Today, owing to the effectiveness of ART, the HIV-infected population is aging and HIV infection has become a chronic illness. Non-AIDS comorbidities are increasing, and the spectrum of HIV-related thoracic diseases is evolving. In developed countries, bacterial pneumonia has become more common than Pneumocystis pneumonia. Its imaging appearance depends on the responsible organism, most commonly Streptococcus pneumoniae. Mycobacterium tuberculosis continues to be a major threat. Its imaging patterns vary depending on CD4 count. Primary lung cancer and Hodgkin lymphoma are two important non–AIDS-defining malignancies that are increasingly encountered at chest imaging. Human herpesvirus 8, also known as Kaposi sarcoma–associated herpesvirus (KSHV), is strongly linked to HIV-related diseases, including Kaposi sarcoma, multicentric Castleman disease, KSHV inflammatory cytokine syndrome, and primary effusion lymphoma. Immune reconstitution inflammatory syndrome is a direct complication of ART whose manifestations vary with the underlying disease. Given the high rate of smoking among HIV-infected patients, chronic obstructive pulmonary disease is another important cause of morbidity and mortality. A high degree of suspicion is required for the early diagnosis of pulmonary arterial hypertension and lymphocytic interstitial pneumonia, given their nonspecific manifestations. Finally, multilocular thymic cyst manifests as a cystic anterior mediastinal mass. Recognition of the clinical and radiologic manifestations of these less traditional HIV-related diseases can expedite diagnosis and treatment in the ART era. © RSNA, 2014 PMID:25019430
NASA Astrophysics Data System (ADS)
Yang, Jing; Youssef, Mostafa; Yildiz, Bilge
2018-01-01
In this work, we quantify oxygen self-diffusion in monoclinic-phase zirconium oxide as a function of temperature and oxygen partial pressure. A migration barrier of each type of oxygen defect was obtained by first-principles calculations. Random walk theory was used to quantify the diffusivities of oxygen interstitials by using the calculated migration barriers. Kinetic Monte Carlo simulations were used to calculate diffusivities of oxygen vacancies by distinguishing the threefold- and fourfold-coordinated lattice oxygen. By combining the equilibrium defect concentrations obtained in our previous work together with the herein calculated diffusivity of each defect species, we present the resulting oxygen self-diffusion coefficients and the corresponding atomistically resolved transport mechanisms. The predicted effective migration barriers and diffusion prefactors are in reasonable agreement with the experimentally reported values. This work provides insights into oxygen diffusion engineering in Zr O2 -related devices and parametrization for continuum transport modeling.
Activation volume for phosphorus diffusion in silicon and Si0.93Ge0.07
NASA Astrophysics Data System (ADS)
Zhao, Yuechao; Aziz, Michael J.; Zangenberg, Nikolaj R.; Larsen, Arne Nylandsted
2005-04-01
The hydrostatic pressure dependence of the diffusivity of P in compressively strained Si0.93Ge0.07 and unalloyed Si has been measured. In both cases the diffusivity is almost independent of pressure, characterized by an activation volume V* of (+0.09±0.11) times the atomic volume Ω for the unalloyed Si, and (+0.01±0.06) Ω for Si0.93Ge0.07. The results are used in conjunction with the reported effect of biaxial strain on diffusion normal to the surface to test the prediction for an interstitialcy-based mechanism of Aziz's phenomenological thermodynamic treatment of diffusion under uniform nonhydrostatic stress states. The prediction agrees well with measured behavior, lending additional credence to the interstitial-based mechanism and supporting the nonhydrostatic thermodynamic treatment.
Williams, David; Kadaria, Dipen; Sodhi, Amik; Fox, Roy; Williams, Glenn; Threlkeld, Stephen
2017-01-01
Patient: Female, 23 Final Diagnosis: Chronic granulomatous disease Symptoms: Fever • shortness of breath Medication: — Clinical Procedure: Bronchoscopy Specialty: Pulmonology Objective: Unusual clinical course Background: Chronic Granulomatous Disease (CGD) is a rare immunodeficiency disease caused by a genetic defect in the NADPH (nicotinamide adenine dinucleotide phosphate) oxidase enzyme, resulting in increased susceptibility to bacterial and fungal infections. The inheritance can be X-linked or autosomal recessive. Patients usually present with repeated infections early in life. We present an unusual case of a 23-year-old patient diagnosed with CGD. Case Report: A 23-year-old white woman with no previous history of recurrent infections presented with complaints of fever, shortness of breath, and diffuse myalgia. She had been treated twice for similar complaints recently, but without resolution. She was febrile, tachypneic, tachycardic, and hypoxic at presentation. Physical examination revealed diffuse inspiratory rales. Laboratory results showed leukocytosis. Her initial chest X-ray and CT chest showed reticular nodular interstitial lung disease pattern. Despite being on broad-spectrum antibiotics for 5 days, she continued to require supplemental oxygen and continued to be tachypneic, with minimal activity. Initial diagnostic tests, including bronchoscopy with biopsy and lavage, did not reveal a diagnosis. She then underwent a video-assisted thoracoscopic surgery (VATS) lung biopsy. The biopsy slides showed suppurative granulomatous inflammation affecting greater than 50% of the parenchymal lung surface. Fungal hyphae consistent with Aspergillus were present in those granulomas. A diagnosis of CGD was made and she was started on Voriconazole. She improved with treatment. Her neutrophil burst test showed negative burst on stimulation, indicating phagocytic dysfunction consistent with CGD. Autosomal recessive CGD was confirmed by genetic testing. Conclusions: CGD can present in adulthood without any previous symptoms and signs. Clinicians should consider this disease in patients presenting with recurrent or non-resolving infections. Timely treatment and prophylaxis has been shown to reduce serious infections as well as mortality in these patients. PMID:28377567
NASA Astrophysics Data System (ADS)
Li, Yu-Hao; Zhou, Hong-Bo; Jin, Shuo; Zhang, Ying; Deng, Huiqiu; Lu, Guang-Hong
2017-04-01
We investigate the behaviors of rhenium (Re) and osmium (Os) and their interactions with point defects in tungsten (W) using a first-principles method. We show that Re atoms are energetically favorable to disperse separately in bulk W due to the Re-Re repulsive interaction. Despite the attractive interaction between Os atoms, there is still a large activation energy barrier of 1.10 eV at the critical number of 10 for the formation of Os clusters in bulk W based on the results of the total nucleation free energy change. Interestingly, the presence of vacancy can significantly reduce the total nucleation free energy change of Re/Os clusters, suggesting that vacancy can facilitate the nucleation of Re/Os in W. Re/Os in turn has an effect on the stability of the vacancy clusters (V n ) in W, especially for small vacancy clusters. A single Re/Os atom can raise the total binding energies of V2 and V3 obviously, thus enhancing their formation. Further, we demonstrate that there is a strong attractive interaction between Re/Os and self-interstitial atoms (SIAs). Re/Os could increase the diffusion barrier of SIAs and decrease their rotation barrier, while the interstitial-mediated path may be the optimal diffusion path of Re/Os in W. Consequently, the synergistic effect between Re/Os and point defects plays a key role in Re/Os precipitation and the evolution of defects in irradiated W.
NASA Astrophysics Data System (ADS)
Oh, Gyu-Jin; Lee, Kye-Man; Huh, Moo-Young; Park, Jin Eon; Park, Soo Ho; Engler, Olaf
2017-01-01
Three initial tensile specimens having different textures and, in consequence, different r-values were cut from a sheet of an interstitial-free steel. Using these specimens, the effect of r-value and texture on plastic deformation and the necking behavior were studied by tackling the strain state and texture during tensile tests. A reduced decrease in work hardening rate of tensile specimens with higher r-values led to a slower onset of diffuse necking which offers an increased uniform elongation. A slower reduction in thickness of specimens with a higher r-value provided a favorable resistance against onset of failure by localized necking.
Wolf, Michael S.; Chadha, Ashley D.; Carroll, Clinton M.; Borinstein, Scott C.
2014-01-01
Radiation-induced lung disease is a known complication of therapeutic lung irradiation, but the features have not been well described in children. We report the clinical, radiologic and histologic features of interstitial lung disease (ILD) in a 4-year-old child who had previously received lung irradiation as part of successful treatment for metastatic Wilms tumor. Her radiologic abnormalities and clinical symptoms developed in an indolent manner. Clinical improvement gradually occurred with corticosteroid therapy. However, the observed radiologic progression from interstitial and reticulonodular opacities to diffuse cystic lung disease, with subsequent improvement, is striking and has not been previously described in children. PMID:25434733
Review on first-principles study of defect properties of CdTe as a solar cell absorber
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Ji-Hui; Yin, Wan-Jian; Park, Ji-Sang
2016-07-15
CdTe is one of the leading materials for high-efficiency, low-cost, and thin-film solar cells. In this work, we review the recent first-principles study of defect properties of CdTe and present that: (1) When only intrinsic defects are present, p-type doping in CdTe is weak and the hole density is low due to the relatively deep acceptor levels of Cd vacancy. (2) When only intrinsic defects present, the dominant non-radiative recombination center in p-type CdTe is Te-2+/Cd, which limits the carrier lifetime to be around 200 ns. (3) Extrinsic p-type doping in CdTe by replacing Te with group V elements generallymore » will be limited by the formation of AX centers. This could be overcome through a non-equilibrium cooling process and the hole density can achieve 10^17 cm-3. However, the long-term stability will be a challenging issue. (4) Extrinsic p-type doping by replacing Cd with alkaline group I elements is limited by alkaline interstitials and a non-equilibrium cooling process can efficiently enhance the hole density to the order of 10^17 cm-3. (5) Cu and Cl treatments are discussed. In bulk CdTe, Cu can enhance p-type doping, but Cl is found to be unsuitable for this. Both Cu and Cl show segregation at grain boundaries, especially at those with Te-Te wrong bonds. (6) External impurities are usually incorporated by diffusion. Therefore, the diffusion processes in CdTe are investigated. We find that cation interstitial (Nai, Cui) diffusion follows relatively simple diffusion paths, but anion diffusion (Cli, Pi) follows more complicated paths due to the degenerated defect wavefunctions.« less
Framework 'interstitial' oxygen in La(10)(GeO(4))(5-)(GeO(5))O(2) apatite electrolyte.
Pramana, Stevin S; Klooster, Wim T; White, T J
2007-08-01
Oxygen conduction at low temperatures in apatites make these materials potentially useful as electrolytes in solid-oxide fuel cells, but our understanding of the defect structures enabling ion migration is incomplete. While conduction along [001] channels is dominant, considerable inter-tunnel mobility has been recognized. Using neutron powder diffraction of stoichiometric 'La(10)(GeO(4))(6)O(3)', it has been shown that this compound is more correctly described as an La(10)(GeO(4))(5-)(GeO(5))O(2) apatite, in which high concentrations of interstitial oxygen reside within the channel walls. It is suggested that these framework interstitial O atoms provide a reservoir of ions that can migrate into the conducting channels of apatite, via a mechanism of inter-tunnel oxygen diffusion that transiently converts GeO(4) tetrahedra to GeO(5) distorted trigonal bipyramids. This structural modification is consistent with known crystal chemistry and may occur generally in oxide apatites.
Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro
2012-09-01
Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.
Ali, F S.M.; Stanaway, S E.R.S.; Zakhour, H D.; Spearing, G; Bowen-Jones, D
2003-11-01
Hyperandrogenism in females usually results from ovarian or adrenal pathology. We present a case of virilizaton due to very rare bilateral ovarian diffuse interstitial proliferation of Leydig cells with no tumour or hilar cell hyperplasia identified. Interestingly, the case was further complicated by the finding of high levels of testosterone in one adrenal vein on selective venous sampling (SVS), resulting in an unnecessary unilateral adrenalectomy. Further sampling found high levels also in the ovarian veins, and the condition was finally cured by bilateral oophorectomy.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xu, Haixuan; Osetskiy, Yury N; Stoller, Roger E
The fundamentals of the framework and the details of each component of the self-evolving atomistic kinetic Monte Carlo (SEAKMC) are presented. The strength of this new technique is the ability to simulate dynamic processes with atomistic fidelity that is comparable to molecular dynamics (MD) but on a much longer time scale. The observation that the dimer method preferentially finds the saddle point (SP) with the lowest energy is investigated and found to be true only for defects with high symmetry. In order to estimate the fidelity of dynamics and accuracy of the simulation time, a general criterion is proposed andmore » applied to two representative problems. Applications of SEAKMC for investigating the diffusion of interstitials and vacancies in bcc iron are presented and compared directly with MD simulations, demonstrating that SEAKMC provides results that formerly could be obtained only through MD. The correlation factor for interstitial diffusion in the dumbbell configuration, which is extremely difficult to obtain using MD, is predicted using SEAKMC. The limitations of SEAKMC are also discussed. The paper presents a comprehensive picture of the SEAKMC method in both its unique predictive capabilities and technically important details.« less
Akya, Alisha; Elahi, Azam; Chegenelorestani, Roya; Rezaee, Mahya
2018-01-01
Klebsiella pneumoniae ( K. pneumoniae ) is an important opportunistic pathogen causes serious community and hospital-acquired infections, which is highly resistant to antibiotics. We aimed to determine the frequency of multidrug resistant (MDR) and molecular typing of clinical isolates of K. pneumoniae . One hundred isolates of K. pneumoniae were collected from clinical samples in three general hospitals in Kermanshah. The antimicrobial susceptibility and extended-spectrum beta-lactamases (ESBL) production of isolates were determined using disk diffusion and combined disk methods, respectively. The bla CTX-M gene, class I and II integrons were detected using polymerase chain reaction. The bla CTX-M positive isolates were selected for genotyping using pulsed-field gel electrophoresis (PFGE). MDR phenotype was observed in 56% of isolates. The 40% of isolates were ESBL positive and 35 isolates contained bla CTX-M . Class I and II of integrons were detected in 50 (89.2%) and 39 (69.6%) of MDR isolates, respectively. PFGE patterns of K. pneumoniae bla CTX-M positive isolates indicated 19 clusters (X 1-19 ) with different genotype patterns. The study findings highlight the concern of circulating MDR strains of K. pneumoniae with bla CTX-M and class I and II integrons in Kermanshah hospitals. The presence of integrons among isolates may facilitate the spread of new resistance genes in this bacterium. Therefore, surveillance for the spread of MDR strains of this bacterium is recommended in hospitals.
OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN BULK TUNGSTEN
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.
2015-09-22
We used our recently developed lattice based OKMC code; KSOME [1] to carryout simulations of radiation damage in bulk W. We study the effect of dimensionality of self interstitial atom (SIA) diffusion i.e. 1D versus 3D on the defect accumulation during irradiation with a primary knock-on atom (PKA) energy of 100 keV at 300 K for the dose rates of 10-5 and 10-6 dpa/s. As expected 3D SIA diffusion significantly reduces damage accumulation due to increased probability of recombination events. In addition, dose rate, over the limited range examined here, appears to have no effect in both cases of SIAmore » diffusion.« less
Vaccine-induced canine distemper in European mink, Mustela lutreola.
Sutherland-Smith, M R; Rideout, B A; Mikolon, A B; Appel, M J; Morris, P J; Shima, A L; Janssen, D J
1997-09-01
This report describes vaccine-induced canine distemper virus (CDV) infection in four European mink (Mustela lutreola) induced by the administration of a multivalent, avian-origin vaccine. Clinical signs consisting of seizures, ataxia, facial twitching, oculonasal discharge, hyperkeratosis of footpads, and anorexia developed 16-20 days postvaccination. Conjunctival smears from one animal were positive for CDV antigen by direct fluorescent antibody testing, confirming the clinical diagnosis. The four mink died 16-26 days postvaccination. Gross and microscopic lesions that were diagnostic for CDV infection included interstitial pneumonia, lymphoid depletion, nonsuppurative encephalitis, and dermatitis. Vaccine-strain virus was isolated from tissues of three animals. Cases of vaccine-induced distemper in mustelids using avian-origin vaccine have seldom been reported.
Fermi level dependence of hydrogen diffusivity in GaN
NASA Astrophysics Data System (ADS)
Polyakov, A. Y.; Smirnov, N. B.; Pearton, S. J.; Ren, F.; Theys, B.; Jomard, F.; Teukam, Z.; Dmitriev, V. A.; Nikolaev, A. E.; Usikov, A. S.; Nikitina, I. P.
2001-09-01
Hydrogen diffusion studies were performed in GaN samples with different Fermi level positions. It is shown that, at 350 °C, hydrogen diffusion is quite fast in heavily Mg doped p-type material with the Fermi level close to Ev+0.15 eV, considerably slower in high-resistivity p-GaN(Zn) with the Fermi level Ev+0.9 eV, while for conducting and semi-insulating n-GaN samples with the Fermi level in the upper half of the band gap no measurable hydrogen diffusion could be detected. For these latter samples it is shown that higher diffusion temperature of 500 °C and longer times (50 h) are necessary to incorporate hydrogen to appreciable depth. These findings are in line with previously published theoretical predictions of the dependence of hydrogen interstitials formation in GaN on the Fermi level position.
NASA Astrophysics Data System (ADS)
Stroh, Mark; Zipfel, Warren R.; Williams, Rebecca M.; Ma, Shu Chin; Webb, Watt W.; Saltzman, W. Mark
2004-07-01
Brain-derived neurotrophic factor (BDNF) is a promising therapeutic agent for the treatment of neurodegenerative diseases. However, the limited distribution of this molecule after administration into the brain tissue considerably hampers its efficacy. Here, we show how multiphoton microscopy of fluorescently tagged BDNF in brain-tissue slices provides a useful and rapid screening method for examining the diffusion of large molecules in tissues, and for studying the effects of chemical modifications-for example, conjugating with polyethylene glycol (PEG)-on the diffusion constant. This single variable, obtained by monitoring short-term diffusion in real time, can be effectively used for rational drug design. In this study on fluorescently tagged BDNF and BDNF-PEG, we identify slow diffusion as a major contributing factor to the limited penetration of BDNF, and demonstrate how chemical modification can be used to overcome this barrier.
Ameliorative effects of Qingfei Tongluo formula on experimental mycoplasmal pneumonia in mice.
Jiang, Yong-hong; Yu, Jian-er; Guo, Ai-hua; Li, Xiao; Lin, Yan; Jiang, Zhi-yan; Xiao, Zhen
2016-04-01
Mycoplasma pneumoniae pneumonia (MPP) is a common disease in children. Qingfei Tongluo formula (QTF) has been used for the treatment of MPP clinically, but the chemical constituents and mechanism involved remain unclear. This study aimed to analyze the main chemical constituents and to explore the possible mechanism of action associated with QTF treatment of MPP. Liquid chromatography-mass spectrometry was employed to identify the compounds contained in the QTF extract. A BALB/c mouse model of MP infection was established. After treatment with QTF (0.85 and 1.70 g/kg) for 3 days, hematoxylin and eosin staining was performed in lung tissues for histological examination. Inflammatory cytokines were detected by ELISA. Western blot analysis was used for detecting phosphorylated proteins involved in MAPK and nuclear factor (NF)-κB signaling pathways. In the mouse model, a large amount of pulmonary interstitial infiltration of lymphocytes and plasmacytes were seen as well as bronchus and vasodilation congestion. Following QTF treatment, inflammation was alleviated significantly compared with the model group. Inflammatory cytokines [interleukin (IL)-6, transforming growth factor-β1, IL-8, IL-1β and tumor necrosis factor-α] in bronchoalveolar lavage fluid were decreased dramatically. In addition, we found that QTF inhibited activation of phosphorylation of JNK, ERK and NF-κB. In conclusion, QTF alleviates MPP inflammation possibly via inhibitory activation of MAPK/NF-κB pathways, which can act as a new agent for MPP treatment.
2017-01-01
According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs’ victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD. PMID:28111421
Leem, Jong-Han; Chung, Kyu Hyuck
2016-01-01
According to previous survey, about two million of people were expected to suffer from toxic effects due to humidifier disinfectant (HD), regardless of healing or not. Extremely small group are recognized as HDs' victims. Up to now, previous research tried to focus on interstitial fibrosis on terminal bronchiole because it is specific finding, compared with other diseases. To figure out overall effects from HDs, we recommend adverse outcome pathways (AOPs) as new approach. Reactive oxygen species (ROS) generation, decreased T-cell and pro-inflammatory cytokine release from macrophage could be key events between the exposure to HDs and diseases. ROS generation, decreased cell and pro-inflammatory cytokine release from macrophage could be cause of interstitial fibrosis, pneumonia and many other diseases such as asthma, allergic rhinitis, allergic dermatitis, fetal death, premature baby, autoimmune disease, hepatic toxicity, renal toxicity, cancer, and so on. We predict potential disease candidate by AOPs. We can validate the real risk of the adverse outcome by epidemiologic and toxicologic study using big data such as National Health Insurance data and AOPs knowledge base. Application of these kinds of new methods can find the potential disease list from the exposure to HD.
Self-diffusion of protons in H{sub 2}O ice VII at high pressures: Anomaly around 10 GPa
DOE Office of Scientific and Technical Information (OSTI.GOV)
Noguchi, Naoki, E-mail: noguchi-n@okayama-u.ac.jp; Okuchi, Takuo
2016-06-21
The self-diffusion of ice VII in the pressure range of 5.5–17 GPa and temperature range of 400–425 K was studied using micro Raman spectroscopy and a diamond anvil cell. The diffusion was monitored by observing the distribution of isotope tracers: D{sub 2}O and H{sub 2}{sup 18}O. The diffusion coefficient of hydrogen reached a maximum value around 10 GPa. It was two orders of magnitude greater at 10 GPa than at 6 GPa. Hydrogen diffusion was much faster than oxygen diffusion, which indicates that protonic diffusion is the dominant mechanism for the diffusion of hydrogen in ice VII. This mechanism ismore » in remarkable contrast to the self-diffusion in ice I{sub h} that is dominated by an interstitial mechanism for the whole water molecule. An anomaly around 10 GPa in ice VII indicates that the rate-determining process for the proton diffusion changes from the diffusion of ionic defects to the diffusion of rotational defects, which was suggested by proton conductivity measurements and molecular dynamics simulations.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Al-Amin, M., E-mail: m.al-amin@warwick.ac.uk; Murphy, J. D., E-mail: john.d.murphy@warwick.ac.uk
2016-06-21
We report a systematic study into the effects of long low temperature (≤500 °C) annealing on the lifetime and interstitial iron distributions in as-grown multicrystalline silicon (mc-Si) from different ingot height positions. Samples are characterised in terms of dislocation density, and lifetime and interstitial iron concentration measurements are made at every stage using a temporary room temperature iodine-ethanol surface passivation scheme. Our measurement procedure allows these properties to be monitored during processing in a pseudo in situ way. Sufficient annealing at 300 °C and 400 °C increases lifetime in all cases studied, and annealing at 500 °C was only found to improve relatively poormore » wafers from the top and bottom of the block. We demonstrate that lifetime in poor as-grown wafers can be improved substantially by a low cost process in the absence of any bulk passivation which might result from a dielectric surface film. Substantial improvements are found in bottom wafers, for which annealing at 400 °C for 35 h increases lifetime from 5.5 μs to 38.7 μs. The lifetime of top wafers is improved from 12.1 μs to 23.8 μs under the same conditions. A correlation between interstitial iron concentration reduction and lifetime improvement is found in these cases. Surprisingly, although the interstitial iron concentration exceeds the expected solubility values, low temperature annealing seems to result in an initial increase in interstitial iron concentration, and any subsequent decay is a complex process driven not only by diffusion of interstitial iron.« less
NASA Astrophysics Data System (ADS)
Leroy, Henri-Arthur; Vermandel, Maximilien; Tétard, Marie-Charlotte; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas
2015-03-01
Background Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a local treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen to form cytotoxic species. Fractionation of light delivery may enhance treatment efficiency by restoring tissue oxygenation. Objectives To evaluate the efficiency of light fractionation using MRI imaging, including diffusion and perfusion, compared to histological data. Materials and Methods Thirty-nine "Nude" rats were grafted with human U87 cells into the right putamen. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomized in three groups: without illumination, with monofractionated illumination and the third one with multifractionated light. Treatment effects were assessed with early MRI including diffusion and perfusion sequences. The animals were eventually sacrificed to perform brain histology. Results On MRI, we observed elevated diffusion values in the center of the tumor among treated animals, especially in multifractionated group. Perfusion decreased around the treatment site, all the more in the multifractionated group. Histology confirmed our MRI findings, with a more extensive necrosis and associated with a rarified angiogenic network in the treatment area, after multifractionated PDT. However, we observed more surrounding edema and neovascularization in the peripheral ring after multifractionated PDT. Conclusion Fractionated interstitial PDT induced specific tumoral lesions. The multifractionated scheme was more efficient, inducing increased tumoral necrosis, but it also caused significant peripheral edema and neovascularization. Diffusion and perfusion MRI imaging were able to predict the histological lesions.
Kong, Xiang; Wen, Ji-qiu; Qi, Rong-feng; Luo, Song; Zhong, Jian-hui; Chen, Hui-juan; Ji, Gong-jun; Lu, Guang Ming; Zhang, Long Jiang
2014-01-01
Abstract To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P < 0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P < 0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P > 0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes. PMID:25526483
Toussaint, Magali; Pinel, Sophie; Auger, Florent; Durieux, Nicolas; Thomassin, Magalie; Thomas, Eloise; Moussaron, Albert; Meng, Dominique; Plénat, François; Amouroux, Marine; Bastogne, Thierry; Frochot, Céline; Tillement, Olivier; Lux, François; Barberi-Heyob, Muriel
2017-01-01
Despite recent progress in conventional therapeutic approaches, the vast majority of glioblastoma recur locally, indicating that a more aggressive local therapy is required. Interstitial photodynamic therapy (iPDT) appears as a very promising and complementary approach to conventional therapies. However, an optimal fractionation scheme for iPDT remains the indispensable requirement. To achieve that major goal, we suggested following iPDT tumor response by a non-invasive imaging monitoring. Nude rats bearing intracranial glioblastoma U87MG xenografts were treated by iPDT, just after intravenous injection of AGuIX® nanoparticles, encapsulating PDT and imaging agents. Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) allowed us an original longitudinal follow-up of post-treatment effects to discriminate early predictive markers. We successfully used conventional MRI, T2 star (T2*), Diffusion Weighted Imaging (DWI) and MRS to extract relevant profiles on tissue cytoarchitectural alterations, local vascular disruption and metabolic information on brain tumor biology, achieving earlier assessment of tumor response. From one day post-iPDT, DWI and MRS allowed us to identify promising markers such as the Apparent Diffusion Coefficient (ADC) values, lipids, choline and myoInositol levels that led us to distinguish iPDT responders from non-responders. All these responses give us warning signs well before the tumor escapes and that the growth would be appreciated.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hsu, William, E-mail: william.hsu@utexas.edu; Kim, Taegon; Chou, Harry
2016-07-07
Although the diffusion control and dopant activation of Ge p-type junctions are straightforward when using B{sup +} implantation, the use of the heavier BF{sub 2}{sup +} ions or even BF{sup +} is still favored in terms of shallow junction formation and throughput—because implants can be done at higher energies, which can give higher beam currents and beam stability—and thus the understanding of the effect of F co-doping becomes important. In this work, we have investigated diffusion and end-of-range (EOR) defect formation for B{sup +}, BF{sup +}, and BF{sub 2}{sup +} implants in crystalline and pre-amorphized Ge, employing rapid thermal annealingmore » at 600 °C and 800 °C for 10 s. It is demonstrated that the diffusion of B is strongly influenced by the temperature, the presence of F, and the depth of amorphous/crystalline interface. The B and F diffusion profiles suggest the formation of B–F complexes and enhanced diffusion by interaction with point defects. In addition, the strong chemical effect of F is found only for B in Ge, while such an effect is vanishingly small for samples implanted with F alone, or co-implanted with P and F, as evidenced by the high residual F concentration in the B-doped samples after annealing. After 600 °C annealing for 10 s, interstitial-induced compressive strain was still observed in the EOR region for the sample implanted with BF{sup +}, as measured by X-ray diffraction. Further analysis by cross-sectional transmission electron microscopy showed that the {311} interstitial clusters are the majority type of EOR defects. The impact of these {311} defects on the electrical performance of Ge p{sup +}/n junctions formed by BF{sup +} implantation was evaluated.« less
Determination of krypton diffusion coefficients in uranium dioxide using atomic scale calculations
Vathonne, Emerson; Andersson, David Ragnar Anders; Freyss, Michel; ...
2016-12-16
We present a study of the diffusion of krypton in UO 2 using atomic scale calculations combined with diffusion models adapted to the system studied. The migration barriers of the elementary mechanisms for interstitial or vacancy assisted migration are calculated in the DFT + U framework using the nudged elastic band method. The attempt frequencies are obtained from the phonon modes of the defect at the initial and saddle points using empirical potential methods. The diffusion coefficients of Kr in UO 2 are then calculated by combining this data with diffusion models accounting for the concentration of vacancies and themore » interaction of vacancies with Kr atoms. We determined the preferred mechanism for Kr migration and the corresponding diffusion coefficient as a function of the oxygen chemical potential μ O or nonstoichiometry. For very hypostoichiometric (or U-rich) conditions, the most favorable mechanism is interstitial migration. For hypostoichiometric UO 2, migration is assisted by the bound Schottky defect and the charged uranium vacancy, V U 4–. Around stoichiometry, migration assisted by the charged uranium–oxygen divacancy (V UO 2–) and V U 4– is the favored mechanism. Finally, for hyperstoichiometric or O-rich conditions, the migration assisted by two V U 4– dominates. Kr migration is enhanced at higher μ O, and in this regime, the activation energy will be between 4.09 and 0.73 eV depending on nonstoichiometry. The experimental values available are in the latter interval. Since it is very probable that these values were obtained for at least slightly hyperstoichiometric samples, our activation energies are consistent with the experimental data, even if further experiments with precisely controlled stoichiometry are needed to confirm these results. Finally, the mechanisms and trends with nonstoichiometry established for Kr are similar to those found in previous studies of Xe.« less
Experimental studies of aerosol- cloud droplet interactions at the puy de Dome observatory (France)
NASA Astrophysics Data System (ADS)
Laj, P.; Dupuy, R.; Sellegri, K.; Pichon, J.; Fournol, J.; Cortes, L.; Preunkert, S.; Legrand, M.
2001-05-01
The interactions between aerosol particles, gases and cloud droplets were studied at the puy de Dome cloud station (France, 1465 a.s.l.) during winter 2000. The partitioning of gas and aerosol species between interstitial and condensed phases is achieved using a series of instrumentation including a newly developed dual counter-flow virtual impactor (CVI)/ Round jet impactor (RJI) system. The RJI/CVI system, coupled with measurement of cloud microphysical properties, provided direct observation of number and mass partitioning of aerosols under different air mass conditions. Preliminary results from this field experiment allowed for the characterization of size segregated chemical composition of CCNs and of interstitial aerosols by means of gravimetric analysis and ion chromatography. It appears that CCNs are clearly enriched in soluble species as respect to interstitial aerosols. We found evidences of limited growth of Ca2+ - rich coarse particles (>1 μm) that did not form droplets larger than the 5 μm CVI cut-off. The number partitioning of aerosol particles between interstitial and condensed phases clearly depends upon cloud microphysics and aerosol properties and therefore undergoes different behaviour according to air mass origin. However, results cannot be fully explained by diffusion growth alone, in particular for high cloud LWC.
Stochastic annealing simulations of defect interactions among subcascades
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heinisch, H.L.; Singh, B.N.
1997-04-01
The effects of the subcascade structure of high energy cascades on the temperature dependencies of annihilation, clustering and free defect production are investigated. The subcascade structure is simulated by closely spaced groups of lower energy MD cascades. The simulation results illustrate the strong influence of the defect configuration existing in the primary damage state on subsequent intracascade evolution. Other significant factors affecting the evolution of the defect distribution are the large differences in mobility and stability of vacancy and interstitial defects and the rapid one-dimensional diffusion of small, glissile interstitial loops produced directly in cascades. Annealing simulations are also performedmore » on high-energy, subcascade-producing cascades generated with the binary collision approximation and calibrated to MD results.« less
Liu, Jien-Wei; Ko, Wen-Chien; Huang, Cheng-Hua; Liao, Chun-Hsing; Lu, Chin-Te; Chuang, Yin-Ching; Tsao, Shih-Ming; Chen, Yao-Shen; Liu, Yung-Ching; Chen, Wei-Yu; Jang, Tsrang-Neng; Lin, Hsiu-Chen; Chen, Chih-Ming; Shi, Zhi-Yuan; Pan, Sung-Ching; Yang, Jia-Ling; Kung, Hsiang-Chi; Liu, Chun-Eng; Cheng, Yu-Jen; Chen, Yen-Hsu; Lu, Po-Liang; Sun, Wu; Wang, Lih-Shinn; Yu, Kwok-Woon; Chiang, Ping-Cherng; Lee, Ming-Hsun; Lee, Chun-Ming; Hsu, Gwo-Jong
2012-01-01
The Tigecycline In Vitro Surveillance in Taiwan (TIST) study, initiated in 2006, is a nationwide surveillance program designed to longitudinally monitor the in vitro activity of tigecycline against commonly encountered drug-resistant bacteria. This study compared the in vitro activity of tigecycline against 3,014 isolates of clinically important drug-resistant bacteria using the standard broth microdilution and disk diffusion methods. Species studied included methicillin-resistant Staphylococcus aureus (MRSA; n = 759), vancomycin-resistant Enterococcus faecium (VRE; n = 191), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (n = 602), ESBL-producing Klebsiella pneumoniae (n = 736), and Acinetobacter baumannii (n = 726) that had been collected from patients treated between 2008 and 2010 at 20 hospitals in Taiwan. MICs and inhibition zone diameters were interpreted according to the currently recommended U.S. Food and Drug Administration (FDA) criteria and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. The MIC90 values of tigecycline against MRSA, VRE, ESBL-producing E. coli, ESBL-producing K. pneumoniae, and A. baumannii were 0.5, 0.125, 0.5, 2, and 8 μg/ml, respectively. The total error rates between the two methods using the FDA criteria were high: 38.4% for ESBL-producing K. pneumoniae and 33.8% for A. baumannii. Using the EUCAST criteria, the total error rate was also high (54.6%) for A. baumannii isolates. The total error rates between these two methods were <5% for MRSA, VRE, and ESBL-producing E. coli. For routine susceptibility testing of ESBL-producing K. pneumoniae and A. baumannii against tigecycline, the broth microdilution method should be used because of the poor correlation of results between these two methods. PMID:22155819
Depeursinge, Adrien; Chin, Anne S.; Leung, Ann N.; Terrone, Donato; Bristow, Michael; Rosen, Glenn; Rubin, Daniel L.
2014-01-01
Objectives We propose a novel computational approach for the automated classification of classic versus atypical usual interstitial pneumonia (UIP). Materials and Methods 33 patients with UIP were enrolled in this study. They were classified as classic versus atypical UIP by a consensus of two thoracic radiologists with more than 15 years of experience using the American Thoracic Society evidence–based guidelines for CT diagnosis of UIP. Two cardiothoracic fellows with one year of subspecialty training provided independent readings. The system is based on regional characterization of the morphological tissue properties of lung using volumetric texture analysis of multiple detector CT images. A simple digital atlas with 36 lung subregions is used to locate texture properties, from which the responses of multi-directional Riesz wavelets are obtained. Machine learning is used to aggregate and to map the regional texture attributes to a simple score that can be used to stratify patients with UIP into classic and atypical subtypes. Results We compared the predictions based on regional volumetric texture analysis with the ground truth established by expert consensus. The area under the receiver operating characteristic curve of the proposed score was estimated to be 0.81 using a leave-one-patient-out cross-validation, with high specificity for classic UIP. The performance of our automated method was found to be similar to that of the two fellows and to the agreement between experienced chest radiologists reported in the literature. However, the errors of our method and the fellows occurred on different cases, which suggests that combining human and computerized evaluations may be synergistic. Conclusions Our results are encouraging and suggest that an automated system may be useful in routine clinical practice as a diagnostic aid for identifying patients with complex lung disease such as classic UIP, obviating the need for invasive surgical lung biopsy and its associated risks. PMID:25551822
Shvedova, A A; Kisin, E R; Murray, A R; Mouithys-Mickalad, A; Stadler, K; Mason, R P; Kadiiska, M
2014-08-01
Nanomaterials are being utilized in an increasing variety of manufactured goods. Because of their unique physicochemical, electrical, mechanical, and thermal properties, single-walled carbon nanotubes (SWCNTs) have found numerous applications in the electronics, aerospace, chemical, polymer, and pharmaceutical industries. Previously, we have reported that pharyngeal exposure of C57BL/6 mice to SWCNTs caused dose-dependent formation of granulomatous bronchial interstitial pneumonia, fibrosis, oxidative stress, acute inflammatory/cytokine responses, and a decrease in pulmonary function. In the current study, we used electron spin resonance (ESR) to directly assess whether exposure to respirable SWCNTs caused formation of free radicals in the lungs and in two distant organs, the heart and liver. Here we report that exposure to partially purified SWCNTs (HiPco technique, Carbon Nanotechnologies, Inc., Houston, TX, USA) resulted in the augmentation of oxidative stress as evidenced by ESR detection of α-(4-pyridyl-1-oxide)-N-tert-butylnitrone spin-trapped carbon-centered lipid-derived radicals recorded shortly after the treatment. This was accompanied by a significant depletion of antioxidants and elevated biomarkers of inflammation presented by recruitment of inflammatory cells and an increase in proinflammatory cytokines in the lungs, as well as development of multifocal granulomatous pneumonia, interstitial fibrosis, and suppressed pulmonary function. Moreover, pulmonary exposure to SWCNTs also caused the formation of carbon-centered lipid-derived radicals in the heart and liver at later time points (day 7 postexposure). Additionally, SWCNTs induced a significant accumulation of oxidatively modified proteins, increase in lipid peroxidation products, depletion of antioxidants, and inflammatory response in both the heart and the liver. Furthermore, the iron chelator deferoxamine noticeably reduced lung inflammation and oxidative stress, indicating an important role for metal-catalyzed species in lung injury caused by SWCNTs. Overall, we provide direct evidence that lipid-derived free radicals are a critical contributor to tissue damage induced by SWCNTs not only in the lungs, but also in distant organs. Published by Elsevier Inc.
Petkova, D; Xaubet, A; Picado, C; Filella, X; Agusti, C; Luburich, P; Rodriguez-Roisin, R
2000-04-01
Several studies have been carried out to clarify the relationship between CD30 expression and Th2 lymphocytes, although the results have been controversial. To investigate whether CD30 is a useful marker for Th2 lymphocytes in bronchoalveolar lavage (BAL) in interstitial lung diseases (ILD), we studied six control subjects and 31 patients with ILD (12 with idiopathic pulmonary fibrosis, seven with hypersensitivity pneumonitis, three with chronic eosinophilic pneumonia and nine with sarcoidosis). The levels of interleukin-5 (IL-5) (secreted by Th2 cells), interferon-gamma (IFNgamma) (secreted by Th1 cells) and the expression of CD30 on lymphocytes were determined in BAL fluid. There were no differences in the percentage of CD30+ lymphocytes between controls and patients with ILD (0.8+0.4% vs. 2+/-0.4%). In order to determine the relationship between Th2 cells and CD30 expression, we divided the patients into two groups according to BAL IL-5 levels. Group I consisted of eight patients (three chronic eosinophilic pneumonia, three hypersensitivity pneumonitis, two idiopathic pulmonary fibrosis) with high IL-5 levels (298+/-138 pg ml(-1)). Group II consisted of the remaining 23 ILD patients with normal IL-5 levels (0.9+/-0.6 pg ml(-1)). The percentage of eosinophils in BAL fluid was significantly higher in group I compared with group 11 (34+/-16% vs. 3+/-1%, P < 0.05). A correlation between CD30+ lymphocytes and IL-5 in group 1 was not shown. There were no differences in the number of CD30+ I we found a significant correlation between IL-5 levels and the percentage of eosinophils (r = 0.95, P < 0.0001). Our results suggest that CD30 does not appear to be a useful marker for Th2 lymphocytes in BAL from patients with ILD.
An Exome Sequencing Study to Assess the Role of Rare Genetic Variation in Pulmonary Fibrosis.
Petrovski, Slavé; Todd, Jamie L; Durheim, Michael T; Wang, Quanli; Chien, Jason W; Kelly, Fran L; Frankel, Courtney; Mebane, Caroline M; Ren, Zhong; Bridgers, Joshua; Urban, Thomas J; Malone, Colin D; Finlen Copeland, Ashley; Brinkley, Christie; Allen, Andrew S; O'Riordan, Thomas; McHutchison, John G; Palmer, Scott M; Goldstein, David B
2017-07-01
Idiopathic pulmonary fibrosis (IPF) is an increasingly recognized, often fatal lung disease of unknown etiology. The aim of this study was to use whole-exome sequencing to improve understanding of the genetic architecture of pulmonary fibrosis. We performed a case-control exome-wide collapsing analysis including 262 unrelated individuals with pulmonary fibrosis clinically classified as IPF according to American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines (81.3%), usual interstitial pneumonia secondary to autoimmune conditions (11.5%), or fibrosing nonspecific interstitial pneumonia (7.2%). The majority (87%) of case subjects reported no family history of pulmonary fibrosis. We searched 18,668 protein-coding genes for an excess of rare deleterious genetic variation using whole-exome sequence data from 262 case subjects with pulmonary fibrosis and 4,141 control subjects drawn from among a set of individuals of European ancestry. Comparing genetic variation across 18,668 protein-coding genes, we found a study-wide significant (P < 4.5 × 10 -7 ) case enrichment of qualifying variants in TERT, RTEL1, and PARN. A model qualifying ultrarare, deleterious, nonsynonymous variants implicated TERT and RTEL1, and a model specifically qualifying loss-of-function variants implicated RTEL1 and PARN. A subanalysis of 186 case subjects with sporadic IPF confirmed TERT, RTEL1, and PARN as study-wide significant contributors to sporadic IPF. Collectively, 11.3% of case subjects with sporadic IPF carried a qualifying variant in one of these three genes compared with the 0.3% carrier rate observed among control subjects (odds ratio, 47.7; 95% confidence interval, 21.5-111.6; P = 5.5 × 10 -22 ). We identified TERT, RTEL1, and PARN-three telomere-related genes previously implicated in familial pulmonary fibrosis-as significant contributors to sporadic IPF. These results support the idea that telomere dysfunction is involved in IPF pathogenesis.
Sivley, R Michael; Sheehan, Jonathan H; Kropski, Jonathan A; Cogan, Joy; Blackwell, Timothy S; Phillips, John A; Bush, William S; Meiler, Jens; Capra, John A
2018-01-23
Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease. To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function. Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating spatial proximity analyses into other pathogenicity prediction tools may improve accuracy for other genes and genetic diseases.
Campos, Luiz Eduardo Mendes; Pereira, Luiz Fernando Ferreira
2009-06-01
Pulmonary eosinophilia comprises a heterogeneous group of diseases defined by eosinophilia in pulmonary infiltrates (bronchoalveolar lavage fluid) or in tissue (lung biopsy specimens). Although the inflammatory infiltrate is composed of macrophages, lymphocytes, neutrophils and eosinophils, eosinophilia is an important marker for the diagnosis and treatment. Clinical and radiological presentations can include simple pulmonary eosinophilia, chronic eosinophilic pneumonia, acute eosinophilic pneumonia, allergic bronchopulmonary aspergillosis and pulmonary eosinophilia associated with a systemic disease, such as in Churg-Strauss syndrome and hypereosinophilic syndrome. Asthma is frequently concomitant and can be a prerequisite, as in allergic bronchopulmonary aspergillosis and Churg-Strauss syndrome. In diseases with systemic involvement, the skin, the heart and the nervous system are the most affected organs. The radiological presentation can be typical, or at least suggestive, of one of three types of pulmonary eosinophilia: chronic eosinophilic pneumonia, acute eosinophilic pneumonia and allergic bronchopulmonary aspergillosis. The etiology of pulmonary eosinophilia can be either primary (idiopathic) or secondary, due to known causes, such as drugs, parasites, fungal infection, mycobacterial infection, irradiation and toxins. Pulmonary eosinophilia can be also associated with diffuse lung diseases, connective tissue diseases and neoplasia.
Dutta, Priyanka; Botlani, Mohsen; Varma, Sameer
2014-12-26
The dynamical properties of water at protein-water interfaces are unlike those in the bulk. Here we utilize molecular dynamics simulations to study water dynamics in interstitial regions between two proteins. We consider two natural protein-protein complexes, one in which the Nipah virus G protein binds to cellular ephrin B2 and the other in which the same G protein binds to ephrin B3. While the two complexes are structurally similar, the two ephrins share only a modest sequence identity of ∼50%. X-ray crystallography also suggests that these interfaces are fairly extensive and contain exceptionally large amounts of waters. We find that while the interstitial waters tend to occupy crystallographic sites, almost all waters exhibit residence times of less than hundred picoseconds in the interstitial region. We also find that while the differences in the sequence of the two ephrins result in quantitative differences in the dynamics of interstitial waters, the trends in the shifts with respect to bulk values are similar. Despite the high wetness of the protein-protein interfaces, the dynamics of interstitial waters are considerably slower compared to the bulk-the interstitial waters diffuse an order of magnitude slower and have 2-3 fold longer hydrogen bond lifetimes and 2-1000 fold slower dipole relaxation rates. To understand the role of interstitial waters, we examine how implicit solvent models compare against explicit solvent models in producing ephrin-induced shifts in the G conformational density. Ephrin-induced shifts in the G conformational density are critical to the allosteric activation of another viral protein that mediates fusion. We find that in comparison with the explicit solvent model, the implicit solvent model predicts a more compact G-B2 interface, presumably because of the absence of discrete waters at the G-B2 interface. Simultaneously, we find that the two models yield strikingly different induced changes in the G conformational density, even for those residues whose conformational densities in the apo state are unaffected by the treatment of the bulk solvent. Together, these results show that the explicit treatment of interstitial water molecules is necessary for a proper description of allosteric transitions.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases.
García-Fontán, Eva; Blanco Ramos, Montserrat; García, Jose Soro; Carrasco, Rommel; Cañizares, Miguel Ángel; González Piñeiro, Ana
2018-05-19
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern. We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea. The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.
Insights into dynamic processes of cations in pyrochlores and other complex oxides
Uberuaga, Blas Pedro; Perriot, Romain
2015-08-26
Complex oxides are critical components of many key technologies, from solid oxide fuel cells and superionics to inert matrix fuels and nuclear waste forms. In many cases, understanding mass transport is important for predicting performance and, thus, extensive effort has been devoted to understanding mass transport in these materials. However, most work has focused on the behavior of oxygen while cation transport has received relatively little attention, even though cation diffusion is responsible for many phenomena, including sintering, radiation damage evolution, and deformation processes. Here, we use accelerated molecular dynamics simulations to examine the kinetics of cation defects in onemore » class of complex oxides, A₂B₂O₇ pyrochlore. In some pyrochlore chemistries, B cation defects are kinetically unstable, transforming to A cation defects and antisites at rates faster than they can diffuse. When this occurs, transport of B cations occurs through defect processes on the A sublattice. Further, these A cation defects, either interstitials or vacancies, can interact with antisite disorder, reordering the material locally, though this process is much more efficient for interstitials than vacancies. Whether this behavior occurs in a given pyrochlore depends on the A and B chemistry. Pyrochlores with a smaller ratio of cation radii exhibit this complex behavior, while those with larger ratios exhibit direct migration of B interstitials. Similar behavior has been reported in other complex oxides such as spinels and perovskites, suggesting that this coupling of transport between the A and B cation sublattices, while not universal, occurs in many complex oxide.« less
Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton
2010-11-01
The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.
Phyllanthus wightianus Müll. Arg.: A Potential Source for Natural Antimicrobial Agents
Natarajan, D.; Srinivasan, R.; Shivakumar, M. S.
2014-01-01
Phyllanthus wightianus belongs to Euphorbiaceae family having ethnobotanical importance. The present study deals with validating the antimicrobial potential of solvent leaf extracts of P. wightianus. 11 human bacterial pathogens (Bacillus subtilis, Streptococcus pneumoniae, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, Shigella flexneri, Proteus vulgaris, and Serratia marcescens) and 4 fungal pathogens (Candida albicans, Cryptococcus neoformans, Mucor racemosus, and Aspergillus niger) were also challenged with solvent leaf extracts usingagar well and disc diffusion methods. Further, identification of the active component present in the bioactive extract was done using GC-MS analysis. Results show that all extracts exhibited broad spectrum (6–29 mm) of antibacterial activity on most of the tested organisms. The results highlight the fact that the well in agar method was more effective than disc diffusion method. Significant antimicrobial activity was detected in methanol extract against S. pneumoniae (29 mm) with MIC and MBC values of 15.62 μg/mL. GC-MS analysis revealed that 29 bioactive constituents were present in methanolic extract of P. wightianus, of which 9,12-octadecaenioic acid (peak area 22.82%; RT-23.97) and N-hexadecanoic acid (peak area 21.55% RT-21.796) are the major compounds. The findings of this study show that P. wightianus extracts may be used as an anti-infective agent in folklore medicine. PMID:24883301
Kreijtz, Joost H C M; Wiersma, Lidewij C M; De Gruyter, Heidi L M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; Stittelaar, Koert J; Fouchier, Ron A M; Osterhaus, Albert D M E; Sutter, Gerd; Rimmelzwaan, Guus F
2015-03-01
Since the first reports in early 2013, >440 human cases of infection with avian influenza A(H7N9) have been reported including 122 fatalities. After the isolation of the first A(H7N9) viruses, the nucleotide sequences became publically available. Based on the coding sequence of the influenza virus A/Shanghai/2/2013 hemagglutinin gene, a codon-optimized gene was synthesized and cloned into a recombinant modified vaccinia virus Ankara (MVA). This MVA-H7-Sh2 viral vector was used to immunize ferrets and proved to be immunogenic, even after a single immunization. Subsequently, ferrets were challenged with influenza virus A/Anhui/1/2013 via the intratracheal route. Unprotected animals that were mock vaccinated or received empty vector developed interstitial pneumonia characterized by a marked alveolitis, accompanied by loss of appetite, weight loss, and heavy breathing. In contrast, animals vaccinated with MVA-H7-Sh2 were protected from severe disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Kinetic Monte Carlo Simulations of Oxygen Diffusion in Environmental Barrier Coating Materials
NASA Technical Reports Server (NTRS)
Good, Brian S.
2017-01-01
Ceramic Matrix Composite (CMC) materials are of interest for use in next-generation turbine engine components, offering a number of significant advantages, including reduced weight and high operating temperatures. However, in the hot environment in which such components operate, the presence of water vapor can lead to corrosion and recession, limiting the useful life of the components. Such degradation can be reduced through the use of Environmental Barrier Coatings (EBCs) that limit the amount of oxygen and water vapor reaching the component. Candidate EBC materials include Yttrium and Ytterbium silicates. In this work we present results of kinetic Monte Carlo (kMC) simulations of oxygen diffusion, via the vacancy mechanism, in Yttrium and Ytterbium disilicates, along with a brief discussion of interstitial diffusion.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Moses, S.C.; Baker, S.R.; Seldin, M.F.
1983-12-01
A homosexual man with A.I.D.S. (acquired immunologic deficiency syndrome) and pneumocystis infestation was found to have diffuse Ga-67 uptake in the lungs with a coincident negative chest x-ray. While Ga-67 accumulates diffusely in the lungs in a variety of conditions, the present case is the first described in a patient with A.I.D.S. in which Ga-67 was positive before roentgenographic abnormalities were demonstrated. Thus, the use of Ga-67 scan, when A.I.D.S. is suspected, could help establish a diagnosis more promptly.
Ab initio modeling of point defects, self-diffusion, and incorporation of impurities in thorium
NASA Astrophysics Data System (ADS)
Daroca, D. Pérez
2017-02-01
Research on Generation-IV nuclear reactors has boosted the investigation of thorium as nuclear fuel. By means of first-principles calculations within the framework of density functional theory, structural properties and phonon dispersion curves of Th are obtained. These results agreed very well with previous ones. The stability and formation energies of vacancies, interstitial and divacancies are studied. It is found that vacancies are the energetically preferred defects. The incorporation energies of He, Xe, and Kr atoms in Th defects are analyzed. Self-diffusion, migration paths and activation energies are also calculated.
NASA Astrophysics Data System (ADS)
Charniy, L. A.; Morozov, A. N.; Bublik, V. T.; Scherbachev, K. D.; Stepantsova, I. V.; Kaganer, V. M.
1992-03-01
Microdefects in dislocation-free Si-doped (n = (1-3) × 10 18cm-3) HB GaAs crystals were studied by X-ray diffuse scattering measured with the help of a triple-crystal diffractometer. The intensity of the diffuse scattering as well as the isointensity contours around different reciprocal lattice points were analysed. A comparison of the measured isointensity contours with the theoretically calculated ones showed that the microdefects detected are interstitial dislocation loops with the Burgers vectors b = {1}/{2}<110 #3862;; lying in the planes #38;{110} and {111}. The mean radius of the dislocation loops R0 was determined using the wave vector q0 alpha; R-10 corresponding to the transmition point where the Huang diffuse scattering I( q) alpha q-2 ( q < q0) changed to the asymptotic scattering I( q) alpha q-4 ( q #62 q0). The analysis of a D-shaped cross-sectional (111) wafer cut from the end part of the HB ingot showed that R0 changed smoothly along the [ overline211] symmetry axis of the wafer. The highly inhomogeneous "new-moon"-like distribution of the non-dislocational etch-pits was also obtained. The maximal loop radius obtained at the edges of the wafer, R 0 = 1 μm, corresponds to the wafer area enriched with etch-pits and the minimal one, R 0 = 0.3 μm, corresponds to the bound of the new-moon-like area denuded from etch-pits. Microdefects of a new type were detected in the denuded area. These microdefects consist of nuclei, 0.1 μm in radius, and an extended atmosphere of interstitials. The minimal microdefect radius in the centre of the wafer corresponds to the maximum local value of the lattice parameter a = 5.655380 Å, and the minimum local value a = 5.65372 Å was obtained at the wafer edges enriched with microdefect-related etch-pits. Absolute X-ray diffuse intensity measurements were used for microdefect concentration determination. Normalization of I( q) was based on the comparison of the Huang intensity with the thermal diffuse scattering intensity which is predominant for the wave vector q å R-10. The microdefect concentration determined in this way appeared to be 4 × 10 9 cm -3 at the edges of the wafer and 4 × 10 11 cm -3 at the centre of the new-moon-like etch-pit denuded zone. The number of interstitial atoms forming dislocation loops is shown to be the same across the area of the wafer and equal to 10 16 cm -3.
Mirzaii, Mehdi; Jamshidi, Sanaz; Zamanzadeh, Maryam; Marashifard, Masoud; Malek Hosseini, Seyed Ali Asghar; Haeili, Mehri; Jahanbin, Fariba; Mansouri, Fariba; Darban-Sarokhalil, Davood; Khoramrooz, Seyed Sajjad
2018-06-01
Fluoroquinolones (FQs) are recommended as the drugs of choice for the empirical treatment of urinary tract infections (UTIs). This study investigated the molecular determinants of FQ resistance in Escherichia coli and Klebsiella pneumoniae isolates in Iran. A total of 364 clinical isolates of E. coli (n=144) and K. pneumoniae (n=220) were collected from patients with UTI. Susceptibility of the isolates to ciprofloxacin, levofloxacin, gatifloxacin and nalidixic acid was evaluated by disk diffusion. The presence of qnrA, qnrB and qnrS genes was assessed by PCR. Nucleotide sequences of the gyrA and parC genes were determined. Eighty-seven (60.4%) and 15 (6.8%) E. coli and K. pneumoniae isolates, respectively, were resistant to at least one of the tested FQs. Plasmid-mediated quinolone resistance (PMQR) genes were detected in 12.6% and 60.0% of FQ-resistant E. coli and K. pneumoniae, respectively. Whilst qnrB predominated in K. pneumoniae, qnrS was the most prevalent PMQR gene in E. coli. S83L (98.9%) and D87N (59.8%) were the most frequent mutations identified in GyrA of E. coli, and 55.2% (n=48) of FQ-resistant E. coli isolates had mutation in ParC harbouring S80I and E84V substitutions. The GyrAS83L substitution was found in only one FQ-resistant K. pneumoniae isolate. FQ resistance was much more common in E. coli isolates than in K. pneumoniae. Whilst mutations in the drug target-encoding genes gyrA and parC were the major mechanisms involved in FQ resistance in E. coli, PMQR determinants commonly mediated FQ resistance in K. pneumoniae. Copyright © 2018. Published by Elsevier Ltd.
Improving nanoparticle diffusion through tumor collagen matrix by photo-thermal gold nanorods
NASA Astrophysics Data System (ADS)
Raeesi, Vahid; Chan, Warren C. W.
2016-06-01
Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome.Collagen (I) impairs the targeting of nanoparticles to tumor cells by obstructing their diffusion inside dense tumor interstitial matrix. This potentially makes large nanoparticles (>50 nm) reside near the tumor vessels and thereby compromises their functionality. Here we propose a strategy to locally improve nanoparticle transport inside collagen (I) component of the tumor tissue. We first used heat generating gold nanorods to alter collagen (I) matrix by local temperature elevation. We then explored this impact on the transport of 50 nm and 120 nm inorganic nanoparticles inside collagen (I). We demonstrated an increase in average diffusivity of 50 nm and 120 nm in the denatured collagen (I) by ~14 and ~21 fold, respectively, compared to intact untreated collagen (I) matrix. This study shows how nanoparticle-mediated hyperthermia inside tumor tissue can improve the transport of large nanoparticles through collagen (I) matrix. The ability to increase nanoparticles diffusion inside tumor stroma allows their targeting or other functionalities to take effect, thereby significantly improving cancer therapeutic or diagnostic outcome. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08463f
NASA Astrophysics Data System (ADS)
Ohta, Hiromichi; Watanabe, Takanobu; Ohdomari, Iwao
2008-10-01
Potential energy distribution of interstitial O2 molecule in the vicinity of SiO2/Si(001) interface is investigated by means of classical molecular simulation. A 4-nm-thick SiO2 film model is built by oxidizing a Si(001) substrate, and the potential energy of an O2 molecule is calculated at Cartesian grid points with an interval of 0.05 nm in the SiO2 film region. The result shows that the potential energy of the interstitial site gradually rises with approaching the interface. The potential gradient is localized in the region within about 1 nm from the interface, which coincides with the experimental thickness of the interfacial strained layer. The potential energy is increased by about 0.62 eV at the SiO2/Si interface. The result agrees with a recently proposed kinetic model for dry oxidation of silicon [Phys. Rev. Lett. 96, 196102 (2006)], which argues that the oxidation rate is fully limited by the oxidant diffusion.
Release of enzymes from cells: transport and distribution within the extracellular space.
Mattenheimer, H; Friedel, R
1977-01-01
The distribution in the extracellular space of enzymes released from organ cells was investigated using three models: (1) comparison of enzyme activities in blood plasma and lymph of the ductus thoracicus (dog) and plasma and intestinal lymph (rat); (2) i.v. injection of heterologous, homologous and autologous enzymes in order to increase acutely the activities and to measure the rate constants for the distribution and elimination of the enzymes (rat); or (3) plasmapheresis in order to create an enzyme activity gradient from the interstitial space and to determine the rate constants for the reestablishment of the equilibrium between the extra and intravascular compartments (rat). The results suggest that the enzymes are mainly released into the interstitial fluid and transported via the lymph into the intravascular compartment. From there the enzymes diffuse back into the interstitial compartment and are eliminated by a yet unknown mechanism. Transport of enzymes across the capillary membranes in both directions depends on (1) the permeability of the capillary membranes, which varies from region to region and (2) the molecular seizes of the enzymes.
Modelling mass and heat transfer in nano-based cancer hyperthermia.
Nabil, M; Decuzzi, P; Zunino, P
2015-10-01
We derive a sophisticated mathematical model for coupled heat and mass transport in the tumour microenvironment and we apply it to study nanoparticle delivery and hyperthermic treatment of cancer. The model has the unique ability of combining the following features: (i) realistic vasculature; (ii) coupled capillary and interstitial flow; (iii) coupled capillary and interstitial mass transfer applied to nanoparticles; and (iv) coupled capillary and interstitial heat transfer, which are the fundamental mechanisms governing nano-based hyperthermic treatment. This is an improvement with respect to previous modelling approaches, where the effect of blood perfusion on heat transfer is modelled in a spatially averaged form. We analyse the time evolution and the spatial distribution of particles and temperature in a tumour mass treated with superparamagnetic nanoparticles excited by an alternating magnetic field. By means of numerical experiments, we synthesize scaling laws that illustrate how nano-based hyperthermia depends on tumour size and vascularity. In particular, we identify two distinct mechanisms that regulate the distribution of particle and temperature, which are characterized by perfusion and diffusion, respectively.
Interstitial lung disease induced by alectinib (CH5424802/RO5424802).
Ikeda, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Sakai, Takahiro; Sone, Naoyuki; Nishiyama, Akihiro; Niwa, Takashi; Hotta, Machiko; Tanaka, Tomohiro; Ishida, Tadashi
2015-02-01
A 75-year-old woman with anaplastic lymphoma kinase (ALK)-rearranged Stage IV lung adenocarcinoma was administered the selective anaplastic lymphoma kinase inhibitor, alectinib, as a third-line treatment in a Phase 1-2 study. On the 102nd day, chest computed tomography showed diffuse ground glass opacities. Laboratory data revealed high serum levels of KL-6, SP-D and lactate dehydrogenase without any clinical symptoms. There was no evidence of infection. Marked lymphocytosis was seen in bronchoalveolar lavage fluid analysis, and transbronchial lung biopsy showed mild thickening of alveolar septa and lymphocyte infiltration. Interstitial lung disease was judged to be related to alectinib based on improvements in imaging findings and serum biomarkers after discontinuation of alectinib. To our knowledge, this is the first reported case of alectinib-induced interstitial lung disease. Alectinib is a promising drug for ALK-rearranged non-small cell lung cancer. Clinical trials of this selective anaplastic lymphoma kinase inhibitor will facilitate the meticulous elucidation of its long-term safety profile. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
NASA Astrophysics Data System (ADS)
Hwang, T. Y.; Schoenberger, R. J.; Torgeson, D. R.; Barnes, R. G.
1983-01-01
We report the results of a proton-magnetic-resonance investigation of hydrogen location and motion in the hemihydrides ZrXH0.5 of the metallic layer-structured monohalides ZrX of zirconium (X=Br,Cl). Wide-line and pulsed NMR methods were employed to measure the temperature dependence of the linewidth and second moment and of the spin-lattice relaxation time in the laboratory and rotating frames. The results indicate that hydrogen forms an ordered structure on the tetrahedral (T) interstitial sublattice within the Zr metal bilayers, with some (small) random occupancy of octahedral (O) sites. Two stages of motional narrowing observed in the wide-line measurements and double minima found in the relaxation times are consistent with the occurrence of essentially independent hydrogen motional processes on the T and O interstitial sublattices. Hydrogen site occupancy probabilities, jump frequencies, activation energies for hydrogen diffusion, and conduction-electron contributions to the proton spin-lattice relaxation rate are deduced from the measurements.