tbuckley/cabot-search huggingface dataset:
Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1
Authors: H. Fujisawa, Y. Ishii, T. Tateishi, Y. Kawachi, F. Otsuka, M. Amagai, A. Komai, T. Hashimoto
Journal: British Journal of Dermatology (2000)

Pemphigoid nodularis is a rare variant of bullous pemphigoid. We report a 49-year-old Japanese male with clinical and histopathological features of pemphigoid nodularis including circulating and in vivo-bound IgG antibasement membrane zone antibodies and IgA anti-intercellular antibodies. Although the precise molecular target of the IgG autoantibodies could not be determined, intriguingly, immunoblotting showed that the IgA in the patient's serum reacted with the intracellular domain of desmoglein 1, the target antigen in cases of pemphigus foliaceus. However, the IgA did not react with the extracellular domain of desmoglein 1 in sensitive enzyme-linked immunosorbent assay studies using a baculovirus system. These results suggest therefore that these IgA antibodies may possibly not be pathogenic. The mechanism for the production of different autoantibodies is unknown, but this case provides further illustration of the atypical skin immunoreactants often seen in this unusual subtype of bullous pemphigoid.
Lower respiratory tract infections in haematologic patients with and without stemcell transplantation
Authors: Kathleen Jahn, Lilian Junker, Jörg Halter, Daiana Stolz, Michael Tamm
Journal: European Respiratory Journal (2012)

Pulmonary complications are frequent in haematologic patients undergoing chemotherapy or stemcell transplantation. We analysed the diagnostic yield of bronchoscopy with BAL in haematologic patients suffering from symptoms of LRT infection. The assessment of BAL fluid included bacterial/ fungal culture, staining and PCR for mycobacteria, immunohistochemistry for pneumocystis, multiplex viral PCR and cell differentiation. 355 haematologic patients underwent diagnostic bronchoscopy with BAL from October 2009 to January 2012. In 50 cases the patients received high dose chemotherapy, 225 underwent allogenic and 18 autologous stemcell transplantation. 100 patients suffered from fever, 183 from cough and 200 showed an infiltrate on chest CT scan. Bacteria were cultured from 61 BAL fluids: streptococcus pneumoniae (11), staphyloccocus aureus (7), pseudomonas aeruginosa (3), enterococcus (9), moraxella (2), enterobacteriaceae (4), mycoplasma pneumoniae (2), mycoplasma hominis (1), stenotrophomonas maltophilia (2), haemophilus influenzae (4), legionella pneumophila (1). There were 4 cases of pneumocystis jirovecii. In 4 patients we found atypical mycobacteria. Aspergillus species were cultured in 13 cases. In 41.7% viruses were documented. Most often we found rhinovirus (54), followed by CMV (32), HSV (24), parainfluenza (16), RSV (15), human metapneumovirus (13), coronavirus (12), adenovirus (8), EBV and H1N1 (each 4).   Summary and Conclusion :  The incidence of viral infection is very high in patients with pulmonary symptoms and haematological underlying diseases. We recommend to perform BAL with multiplex viral PCR in these patients instead of empiric antibiotic treatment.
Abstract 235: Hypoxia Enhanced Delivery of Mitochondria-Targeted Catalase Protects Choroid Retinal Microvascular Endothelial Cells from Oxidative Stress
Authors: Christopher J Dougherty, Howard Prentice, Kathleen Dorey, Keith A Webster, Janet C Blanks
Journal: Circulation (2007)

Loss of pericytes is a critical event early in the progression of microvascular dysfunction in diabetic retinopathy. Pericyte loss may be linked to high glucose mediated reactive oxygen species generation, blocking N-cadherin trafficking to the endothelial cell surface preventing pericyte recruitment and vessel stabilization. Hydrogen peroxide has been identified as a major free radical produced during high glucose exposure in endothelial cells. The goal of this research is to determine if tissue-specific hypoxia-regulated expression of a mitochondria-targeted catalase can prevent or limit RF/6A microvascular endothelial cell apoptosis and decrease vascular permeability by limiting cellular oxidative stress. For the development of tissue-specific and hypoxia-enhanced expression vectors, promoters were constructed with nine tandem combinations of HREs. This 9x HRE oligomer enhancer was inserted together into a pGL3 firefly luciferase plasmid with the Tie2( short ) promoter for endothelial-specific expression. The 9xHRE-Tie2( sh ) promoter construct was highly selective for RF/6A cells producing a basal amount of mitochondria-targeted catalase equivalent to the Tie2( short ) promoter alone. In response to hypoxia ( pO 2 = 1% ), the 9xHRE-Tie2( short ) promoter showed a 21-fold hypoxia-inducible activation similar in strength to the CMV promoter , measured by dual luciferase assay. The hybrid promoters were incorporated into a replication deficient AAV delivery system for apoptosis and cell culture based endothelial permeability assays. In preliminary assays using RF/6A microvascular endothelial cells, apoptosis was reduced by 58% and permeability was reduced by 46%. The results suggest that mitochondria-targeted catalase protects RF/6A microvascular endothelial cells from apoptosis and reduces endothelial permeability in a high-glucose, low-oxygen environment.
Soluble interleukin-2 receptor levels in patients with undifferentiated and lymphoblastic lymphomas: correlation with survival.
Authors: D K Wagner, J Kiwanuka, B K Edwards, L A Rubin, D L Nelson, I T Magrath
Journal: Journal of Clinical Oncology (1987)

We have been able to detect soluble interleukin-2 receptors (IL-2R) in pretreatment sera from 80 patients with undifferentiated lymphoma (predominantly Burkitt's lymphoma) and lymphoblastic lymphoma. The demonstration of IL-2R in lymphoma-derived cell lines by immunoprecipitation and direct staining indicates that IL-2R is synthesized by the tumor cells. Comparisons were made with two other subject groups: 42 sarcoma patients and 17 normal individuals. The distribution of soluble IL-2R values for lymphoma patients (geometric mean, 1,132 U/mL) was significantly greater than that of sarcoma patients (geometric mean, 332 U/mL; P = .0001) or normal individuals (geometric mean, 238 U/mL; P = .0001). Patients with undifferentiated lymphoma stages B, C, and D had significantly higher soluble IL-2R values (geometric mean, 1,648 U/mL) than stages A and AR (geometric mean, 706 U/mL; P = .0001) or lymphoblastic lymphoma (geometric mean, 826 U/mL; P = .0002). Within the lymphoma group, the soluble IL-2R level was found to be the most significant prognostic indicator of disease-free interval and survival when compared with other previously recognized factors such as histology, stage, bone marrow involvement at presentation, lactic dehydrogenase (LDH), uric acid (UA), and age. No factor was significantly associated with response to therapy, ie, the initial achievement of complete remission (CR) status, although small numbers of patients with a partial response limit interpretation. Soluble IL-2R levels were measured serially in two patients and were found to be elevated at presentation or relapse and to decrease to normal levels during periods of disease remission. IL-2R appears to reflect tumor burden and may prove to be a useful and specific marker for lymphoid tumors.
Inflammatory patterns in asthmatic children based on the measurement of alveolar nitric oxide
Authors: Olaia Sardon, Paula Corcuera, Ane Aldasoro, Javier Korta, Javier Mintegui, Jose Ignacio Emparanza, Eduardo G. Pérez-Yarza
Journal: European Respiratory Journal (2013)

Background:  Nitric oxide (NO) can be measured in proximal [maximum airway NO flux (J9aw NO )] and distal [alveolar NO concentration (CA NO )] airway.   Objective:  To measure J9aw NO  and CA NO  due to define four inflammatory categories in asthmatic children.   Methods:  A cross-sectional study was performed in healthy and asthmatic children. Exhaled NO at multiple flow rates (50, 100 y 200ml/s) was carried out by CLD88sp® analyzer. According to the two-compartment model, CA NO  and J9aw NO  were calculated. A forced spirometry was performed in asthmatic subjects who were classified as follows; type I (normal J9aw NO  and CA NO ), type II (elevated J9aw NO ), type III (elevated J9aw NO  and CA NO ) and type IV (elevated CA NO ). Correlation between fractional exhaled NO (FE NO,50 ), J9aw NO  and CA NO  was studied using Spearman’s rho. Paired comparison were applied with Bonferroni9s multiple comparison adjustment.   Results:  We studied 162 children; 49 (32.23%) were healthy and 103 (67.76%) asthmatic. J9aw NO  and CA NO  were reproducible. In controls FE NO,50  (ppb) (median and range) was 11.5 (1.6-27.3), J9aw NO  (pl/s) was 516 (98.3-1470) and CA NO  (ppb) was 2.2 (0.1-4.5). Asthmatic subjects were classified: 44 (42.7%) in type I, 41 (39.8%) in type II, 14 (13.5%) in type III and 4 (3.88%) in type IV. Strong correlation was found between J9aw NO  and FE NO,50 . A significant increase was found in the number of exacerbations in type III and IV. There was no association between J9aw NO  and CA NO .   Conclusions:  The results for CA NO  and J9aw NO  in healthy controls were similar to those found in other reports. There was no correlation between proximal and distal inflammation. Asthmatic patients with elevated CA NO  presented higher morbidity.
Determinants of non-adherence to pharmacologic allergic rhinitis treatment
Authors: Sandra Baldacci, Sara Maio, Anna Angino, Giuseppe Sarno, Sonia Cerrai, Marzia Simoni, Patrizia Silvi, Francesco Di Pede, Anna Paola Pala, Megon Bresciani, Giovanni Viegi
Journal: European Respiratory Journal (2013)

Background: Allergic rhinitis (AR) is a common condition often coexisting with asthma. Poor adherence with therapy can be the major barrier to achieving disease control, contributing to symptom occurrence, disease exacerbations and higher costs.  Aim: to assess the determinants of non-adherence to pharmacologic allergic rhinitis treatment.  Methods: 107 general practitioners (GP), involved in the Italian “Respiratory allergic diseases: monitoring study of GINA and ARIA guidelines (ARGA)” study, enrolled 1302 patients affected by AR (mean age 39 yrs). For each patient, a self-administered questionnaire on respiratory allergic diseases/symptoms, anti-rhinitis medicines consumption, daily activity limitations, socio-demographic and clinical factors, and the relative form filled in by GP were available. Adherence to treatment was evaluated comparing all the GP prescriptions for AR with medicines consumption reported by the patients.  Results: Overall prevalence rate of adherence was 58.5%, non-adherence was: 25.9% considering other medicines consumption, 15.6% considering no medicine consumption, in respect to GP prescription. By multivariate analysis, non-adherence resulted significantly associated to lack of written therapeutic plan (OR 1.34), daily activity limitations (OR 1.49), low education (OR 1.56), self-medication (OR 1.82), and above all to comorbid asthma (OR 2.23).  Conclusions: Adherence to pharmacologic allergic rhinitis treatment, in real life, continues to be far from optimal. The roles of comorbid asthma, lack of written therapeutic plan, daily activity limitations, low education and self-medication suggest to develop individual programmes based on communication, partnerships and information.
Effect of Methylcellulose on the Murphy-Sturm Lymphosarcoma in Rats&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Allan Lazar, Diane Childress Lazar
Journal: JNCI Journal of the National Cancer Institute (1962)

Sprague-Dawley rats were given intraperitoneal injections of methylcellulose, a colloidal, nondye substance that is stored in the reticuloendothelial system. Injections were begun in various groups at times varying from 10 days before to 8 days after subcutaneous transplantation of Murphy-Sturm lymphosarcoma. The injections had no effect on establishment (takes) or growth of the tumor for the first 10 days after transplantation. Between the 17th and 21st days after transplantation there was complete regression in 38 of 40 rats begun on injections 10 days before transplantation, 15 of 18 rats begun on injections 1 day after transplantation, and 12 of 18 rats begun on injections 8 days after transplantation. Spontaneous regression was observed in 6 of 26 untreated controls.
Pediatric tracheostomy: Indications and complications rate. An experience from a semi-intensive pediatric respiratory unit
Authors: Alessandra Schiavino, Francesco Paolo Rossi, Maria Giovanna Paglietti, Maria Beatrice Chiarini Testa, Teresa Salerno, Renato Cutrera
Journal: European Respiratory Journal (2011)

Tracheostomy in children can be used to provide respiratory support as long-term ventilation/pulmonary toilet, or to bypass proximal airway obstruction. Tracheostomy is burdened by early and late complications which could make difficult hospital and home management.  We performed a single centre Survey from September 2008 to September 2010, identifying early and late complications with the aim to assess the most frequent problems related to tracheostomy management in children.  We administered to the parents a questionnaire in which the different topics were analyzed (indications to tracheostomy, operational tecnique, occurrence of intraoperative, early postoperative (within 24 - 48 hours) and late (after 48 hours) complications and the home care management).  In the 2 years period we evaluated 66 patients (M/F 36/30, mean age 7 years). Indications to tracheostomy were prolonged endotracheal intubation followed by tracheal malacia or stenosis, chronic respiratory failure, central apnoeas and vocal cord paralysis. Patients were affected by genetic or metabolic disorders, cerebral palsy, neuromuscular diseases, congenital heart diseases, tracheal diseases and tumors of the nervous system.  In 65% of cases no complications occurred, while in 5% early complications and in 35% late complications occurred. Only 4 patients died during the Survey period, but not due to tracheostomy complication.  Tracheostomy allows to manage different severe disease in children. The indications for its use have changed over the past decades. Late-onset complications are the most frequent and their knowledge allows to manage the trachestomized patient from hospital staff and home caregivers.
Use of chest computed tomography in the staging of pediatric Wilms' tumor: interobserver variability and prognostic significance.
Authors: J A Wilimas, S C Kaste, W M Kauffman, H Winer-Muram, R Morris, X Luo, J M Boyett
Journal: Journal of Clinical Oncology (1997)

PURPOSE To determine the specificity and prognostic significance of computed tomography (CT) of the chest in pediatric Wilms' tumor. PATIENTS AND METHODS Patients treated for newly diagnosed Wilms' tumor at St Jude Children's Research Hospital between December 1978 and July 1995 were included in the study if an initial chest radiograph and CT were available and if pulmonary involvement (determined by chest radiographs) was absent. For the 202 patients studied, radiographs and CT scans were reviewed blindly and independently by three experienced radiologists for the presence of pulmonary nodules. Outcome variables consisted of intraobserver variability (in a subsample of 40 cases) and concordance between ratings on radiographs and CT scans (both by McNemar's test), interrater variability (by logistic regression), and the cumulative incidence of pulmonary relapse for patients with and without positive CT scans, by reviewer. RESULTS As expected, ratings of pulmonary involvement on radiographs were discordant with CT ratings. There was marked variability among reviewers in CT ratings (P = .0001). Of 202 CT scans, 78 were read as positive by at least one reviewer, 41 were rated positive by only one reviewer, 18 by two reviewers, and 19 by all three. Intrarater variability on repeat reviews was not significant. Patients with nodules identified on CT had a significantly higher pulmonary relapse rate when analyzed separately by reviewer. However, for the 14 patients who had pulmonary relapse, CT scans were rated positive by all three reviewers in only five cases and as negative by all three in another five cases. CONCLUSION The variability in interpretation of chest CT scans in patients with Wilms' tumor limits the predictive utility of these studies. Optimal, standardized techniques and central review are essential if chest CT is to be used for staging in cooperative studies.
Comparison of dynamic contrast-enhanced MRI tracer-kinetic modeling in the lung of smokers v non-smokers
Authors: David Luke, Penny Hubbard, Geoff Parker, Josephine Naish
Journal: European Respiratory Journal (2012)

Previous analysis [1] of dynamic contrast-enhanced (DCE) MRI data in smokers v non-smokers using the extended Kety model revealed increased K trans  in smokers. By fitting the indicator dilution theory (IDT) and adiabatic approximation to the tissue homogeneity (AATH) models we hypothesise that we can decouple the contribution from perfusion and permeability to K trans  to yield enhanced information on lung function and changes due to smoking. Figure 1 summaries the results obtained from the three models used in the smoker study.  K trans  showed a significant difference between smokers and non-smokers from both the extended Kety (p=0.032) and AATH (p=0.038) models. The AATH model implies that the increase in K trans  is due to an increase in the permeability of the capillaries (p=0.030), rather than an increase in blood flow. Both the extended Kety (p=0.026) and AATH (p=0.025) models show a significant increase in the extracellular/extravascular space (EES) in smokers compared to non-smokers.  In conclusion, the use of all three tracer-kinetic models indicate a coherent picture, supporting the hypothesis that increases in K trans  observed in smokers compared to non-smokers are related to increased capillary permeability rather than increased blood flow.  [1] Naish JH et al, Proc. Intl. Soc. Mag. Reson. Med. 16 (2008) 401.
Distribution and Alteration of Lymphatic Vessels in Knee Joints of Normal and Osteoarthritic Mice
Authors: Jixiang Shi, Qianqian Liang, Michael Zuscik, Jie Shen, Di Chen, Hao Xu, Yong‐Jun Wang, Yan Chen, Ronald W. Wood, Jia Li, Brendan F. Boyce, Lianping Xing
Journal: Arthritis & Rheumatology (2013)

To investigate the distribution and alteration of lymphatic vessels and draining function in knee joints of normal and osteoarthritic mice.For the mouse models of osteoarthritis (OA), we used mice with meniscal-ligamentous injury or mice with conditional knockout of the gene for cartilage transforming growth factor β (TGFβ) type II receptor. The severity of cartilage loss and joint destruction was assessed histologically. Capillary and mature lymphatic vessels were identified and analyzed using double immunofluorescence staining and a whole-slide digital imaging system. Lymphatic drainage of knee joints was examined using near-infrared lymphatic imaging. Patient joint specimens obtained during total knee or hip arthroplasty were evaluated to verify the content validity of the mouse findings.Lymphatic vessels were distributed in soft tissues (mainly around the joint capsule, ligaments, fat pads, and muscles of normal knees). The number of lymphatic vessels, particularly the number of capillaries, was significantly increased in joints of mice with mild OA, while the number of mature lymphatic vessels was markedly decreased in joints of mice with severe OA. OA knees exhibited significantly decreased lymph clearance. The number of both capillary and mature lymphatic vessels was significantly decreased in the joints of patients with OA.The whole-slide digital imaging system is a powerful tool, enabling the identification and assessment of lymphatic microvasculature in the entire mouse knee. Lymphatic capillaries and mature vessels are present in various soft tissues around articular spaces. Abnormalities of lymphatic vessels and draining function, including significantly reduced numbers of mature vessels and impaired clearance, are present in OA joints.
Sequential epirubicin-docetaxel-CMF as adjuvant therapy of early breast cancer: Results of the Taxit216 multicenter phase III trial
Authors: A. R. Bianco, A. De Matteis, L. Manzione, C. Boni, S. Palazzo, M. Di Palma, C. Iacono, S. De Placido, P. Papaldo, F. Cognetti
Journal: Journal of Clinical Oncology (2006)

LBA520 Background: Docetaxel is among the most active drugs for advanced breast cancer and it has recently shown efficacy in the adjuvant setting too. This trial is aimed at comparing the efficacy and tolerability of a sequential approach of a chemotherapy combination regimen containing docetaxel to a standard anthracycline-based regimen as adjuvant therapy in node-positive (N+) early breast cancer. Methods: Between July 1998 and July 2002, 972 N+ early breast cancer patients were randomized to either arm A (E→CMF): Epirubicin (E) 120 mg/m 2 iv d1 q21 × 4 cycles followed by Cyclophosphamide 600 mg/m 2 iv, Methotrexate 40 mg/m 2 iv and Fluorouracil 600 mg/m 2 iv (CMF) d1,8 q28 × 4 cycles; or armB (E→T→CMF) in which Docetaxel 100 mg/m 2 iv (T) d1 q21 × 4 cycles was administered after the 4th cycle of E and before the 1st cycle of CMF. Treatment allocation was performed by a computer program using a dynamic balancing algorithm. Balancing factors were: center, lymph node involvement (1 to 3, 4 to 9, &gt;10), estrogen receptor status (negative/positive/unknown), menopausal status (pre/post). During chemotherapy pts were subjected to physical examination and blood chemistry tests every 3 wks, hematology was repeated weekly. At the completion of treatment pts were followed up every 3 months for the first 2 years, every 6 months for years 3–5 and every 12 months for years 6–10. Primary endpoint was disease free survival (DFS) and secondary endpoints were tolerability and overall survival (OS). The study was designed to detect a hazard ratio of 0.70, assuming an α of 0.05 (two sided), a power of 0.80 and an expected DFS in Arm A of 0.65 at 5 years. This required 480 pts per Arm and 250 events. Results: As of March 27th 2006, 486 pts were enrolled in arm A and 486 in arm B, 252 primary events were recorded and the median follow up was 53 months. DFS at 5 years was 0.67 in arm A vs 0.74 in arm B with an estimated Hazard Ratio (HR) of 0.80 (95% CI: 0.62–1.03, p = 0.079). After adjustement by predefined balancing factors (ER, Nodal and menopausal status) the HR was 0.78 (95% CIs: 0.61–1.00; p = 0.05). As for OS, 117 deaths were observed with HR of 0.74 (95% CIs: 0.51–1.07, p = 0.10). Conclusions: Sequential E→T→CMF yields a borderline significant improvement of DFS. Follow up update is still ongoing. [Table: see text]