tbuckley/cabot-search huggingface dataset:
Preoperative Plasma Levels of Transforming Growth Factor Beta<sub>1</sub> (TGF-β<sub>1</sub>) Strongly Predict Progression in Patients Undergoing Radical Prostatectomy
Authors: Shahrokh F. Shariat, Moshe Shalev, Andres Menesses-Diaz, Isaac Yi Kim, Michael W. Kattan, Thomas M. Wheeler, Kevin M. Slawin
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Elevated local and circulating levels of transforming growth factor beta 1 (TGF-β 1 ) have been associated with prostate cancer invasion and metastasis. We tested the hypothesis that preoperative plasma TGF-β 1 levels would independently predict cancer stage and prognosis in patients who undergo radical prostatectomy. PATIENTS AND METHODS: The study group consisted of 120 consecutive patients who underwent radical prostatectomy for clinically localized prostate cancer (median follow-up, 53.8 months). Preoperative plasma levels of TGF-β 1 were measured and correlated with pathologic parameters and clinical outcomes. TGF-β 1 levels also were measured in 44 healthy men without cancer, in 19 men with prostate cancer metastatic to regional lymph nodes, and in 10 men with prostate cancer metastatic to bone. RESULTS: Plasma TGF-β 1 levels in patients with lymph node metastases (14.2 ± 2.6 ng/mL) and bone metastases (15.5 ± 2.4 ng/mL) were higher than those in radical prostatectomy patients (5.2 ± 1.3 ng/mL) and healthy subjects (4.5 ± 1.2 ng/mL) (P &lt; .001). In a preoperative analysis, preoperative plasma TGF-β 1 level and biopsy Gleason sum both were predictors of organ-confined disease (P = .006 and P = .006, respectively) and PSA progression (P &lt; .001 and P = .021, respectively). In a postoperative multivariate analysis, preoperative plasma TGF-β 1 level, pathologic Gleason sum, and surgical margin status were predictors of PSA progression (P = .020,P = .020, and P = .022, respectively). In patients who progressed, preoperative plasma TGF-β 1 levels were higher in those with presumed distant compared with local-only failure (P = .019). CONCLUSION: Plasma TGF-β 1 levels are markedly elevated in men with prostate cancer metastatic to regional lymph nodes and bone. In men without clinical or pathologic evidence of metastases, the preoperative plasma TGF-β 1 level is a strong predictor of biochemical progression after surgery, presumably because of an association with occult metastatic disease present at the time of radical prostatectomy.
An atypical cause of respiratory failure
Authors: James Sylvester
Journal: BMJ (2015)

A 70 year old woman was admitted to the general medical ward (from the emergency department) with a three week history of progressive shortness of breath, which was worse on exertion, and a non-productive cough. She took amlodipine 5 mg for hypertension and lansoprazole 30 mg for gastro-oesophageal reflux disease. She had also been taking immunosuppressive therapy with mycophenolate mofetil 1.5 g twice daily for nine months to treat her lichen planus. She was allergic to tramadol, codeine, and co-trimoxazole. She had received influenza vaccine within the previous 12 months. She was normally active and went on regular five mile walks. On examination she was haemodynamically stable and her respiratory rate was 34 breaths/min, oxygen saturation was 92% on air (arterial oxygen pressure 8.1) although it de-saturated on minimal exertion, and her temperature was 38oC. Auscultation of her chest was unremarkable, with equal air entry bilaterally. The figure⇓ shows her admission chest radiograph. Her haemoglobin was 117 g/L (reference range 115-160), white blood cell count was 8.5×109/L (4-12), neutrophils were 7.4×109/L (2-7.5), and lymphocytes were 0.6×109/L (1.5-4.0). Her estimated glomerular filtration rate was normal (>60 mL/min/1.73m2), as were her liver function tests. Her electrocardiograph showed sinus rhythm with no acute changes. She was treated empirically for community acquired pneumonia (CURB-65 score 1) with benzylpenicillin and clarithromycin. Her admission atypical screen included urine antigen testing for Legionella pneumophila and serum particle agglutination for Mycoplasma pneumonia , both which were negative; a throat swab for influenza was also negative. Blood cultures were negative after five days. During admission her respiratory functions deteriorated, with worsening tachypnoea and hypoxia; she eventually needed intubation and ventilation on the intensive care unit.
Abstract 12667: Serum Brain Natriuretic Peptide Level as a Predictive Factor of Pre-Procedural Thrombi in Atrial Fibrillation
Authors: Takehiro Kimura, Seiji Takatsuki, Shin Kashimura, Yoshinori Katsumata, Takahiko Nishiyama, Nobuhiro Nishiyama, Yoko Tanimoto, Yoshiyasu Aizawa, Keiichi Fukuda
Journal: Circulation (2014)

Introduction: A scheduled catheter ablation for atrial fibrillation (AF) can be postponed due to preexisting thrombi in the left atrial appendage (LAA) identified by trans-esophageal echocardiography (TEE). We aimed to elucidate the predictive factor for thrombi formation. Methods: A total of 372 AF ablation candidates (male, 312; age, 59.8±10.4 years; CHA2DS2-VASc, 1.3±1.3; paroxysmal, 219) were evaluated. Warfarin was administered in 226 patients and dabigatran in 146 patients. A pre-procedural TEE identified thrombi in 24 patients (6.5%: postponed group). The patient background, pre-procedural blood sample data, transthoracic echocardiography (TTE), and TEE were compared between the performed and postponed groups. Results: Thu number of patients with hypertension (P=0.040), vascular disease (P&lt;0.001), sleep apnea syndrome (P&lt;0.001), and a TEE performed during AF (P=0.001) were significantly higher in the postponed group. The type of AF (paroxysmal, 11) and anticoagulants (warfarin, 16) did not differ between the groups. The age (P=0.007), CHA2DS2-VASc score (P=0.015), average flow velocity of the LAA measured using TEE (P&lt;0.001), left ventricular ejection fraction (LVEF; P=0.006), size of the left atrium (LA; P=0.001) measured using TTE, and serum brain natriuretic peptide level (BNP; 82.4±81.4 pg/ml vs. 236.7±141.9; P&lt;0.001) were significantly higher in the postponed group. The prothrombin time (P=0.087) and activated clotting time (P=0.178) did not differ. A multivariate analysis adjusted for the confounding factors such as the age, CHA2DS2-VASc score, LAA flow velocity, LA size and LVEF revealed that a serum BNP level of &gt;135 pg/ml was the independent predictive factor for LAA thrombi (odds ratio, 14.178; 95% confidence interval [CI], 2.907 to 69.149; P=0.001). The area under the receiver operating characteristic (ROC) curve (AUC) for predicting a thrombus with the serum BNP level was 0.860 (95% CI: 0.775 to 0.944). The sensitivity and specificity for predicting a thrombus with a BNP value of &gt;135 pg/ml were 81.8% and 83.6%, respectively. Conclusions: A serum BNP level of &gt;135 pg/ml might be a noninvasive predictive factor for LAA thrombi in AF patients under anticoagulation therapy with warfarin and dabigatran.
Study of the lung cancer patients on hemodialysis (HD) in Japan
Authors: Ryo Matsunuma, Yoshihiro Ohkuni, Akina Komatsu, Kei Nakashima, Nobuhiro Asai, Hideki Makino, Norihiro Kaneko
Journal: European Respiratory Journal (2011)

Introduction:  Early stage lung cancer in patients with end-stage renal disease are often detected by routine chest radiography on hemodialysis (HD) filtration. It is general that standard treatment for hemodialysis patients with lung cancer are not performed because guideline for lung cancer in HD patients is not established yet. Thus, clinicians have difficulty in treating HD patients even though early stage lung cancer is detected.   Method:  We retrospectively analyzed 17 HD patients with lung cancer between April 2004 and September 2010. Patients9 characteristics, histology and stage of lung cancer, treatment and outcome were evaluated.   Results:  A total 17 patients (13 male, 4 female) were eligible in this study. The median age was 72 years (range 54-90). Eleven patients of non-small cell lung cancer (NSCLC) and 1 small cell lung cancer (SCLC) had histological or cytological confirmation and 5 were unknown. They consist of 3 stageI, 1 stageII, 8 stageIII and IV. As for treatment, operation was taken in 3, chemotherapy alone and radiochemotherapy were received in 4 and 1. Nine patients did not receive any treatment since they are too old, had a poor performance status or considered to be intolerable by attending physicians.In terms of chemotherapy, hepatic excretory anti-cancer drugs were used in all the 4 patients. No severe adverse events related-treatment was seen in this study.   Conclusion:  Guideline for HD patients with advanced stage lung cancer should be established.
Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations
Authors: Lori J. Pierce, Myla Strawderman, Steven A. Narod, Ivo Oliviotto, Andrea Eisen, Laura Dawson, David Gaffney, Lawrence J. Solin, Asa Nixon, Judy Garber, Christine Berg, Claudine Isaacs, Ruth Heimann, Olufunmilayo I. Olopade, Bruce Haffty, Barbara L. Weber
Journal: Journal of Clinical Oncology (2000)

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). CONCLUSION: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.
The performance of a new vibrating mesh prototype nebulizer for inhaled biodrugs
Authors: Denis Marchand, Cabrera Maria, Mathieu Pinel, Thibault Nicolini, Laurent Vecellio
Journal: European Respiratory Journal (2014)

Introduction: Biodrugs are used in a wide range of applications and are currently the fastest growing drug category. The majority of these drugs are administered by the intravenous route, one of the possible reasons for the limited efficacy of this therapeutics. Therefore biodrugs delivery directly to the lung via inhalation may hold several advantages of local-acting. The aim of this study was to measure the in vitro performances of a new DTF mesh nebulizer prototype designed for biodrugs. Material and Method: The DTF mesh nebuliser (DTF-VM) and two commercial devices, Microair (Omron, Medix, Clement clack int., UK) and Aeroneb GO (Aerogen, Gallway, Ireland), were used to nebulize Pulmozyme (2.5mL, Roche, Neuilly sur seine, France).The inhalable fraction (IF) was determined by a filtering method using a respiratory pump (Harvard Apparatus, Les Ulis, France). The particle size distribution of mesh nebulizers was measured using laser diffraction (Spraytec). The respirable fraction (RF) was calculated as the percentage of aerosol particles smaller than 5.0 μm predicting the particle penetration in the lungs. Results: The IF was 86% ± 2%, 28% ± 9%, 32% ± 1% and the RF was 90% ± 4%, 42% ± 3.0%, 63% ± 7% respectively for the DTF-VM, Microair and Aeroneb GO. The nebulisation time was 5 ± 1 min, 10 ± 1 min, 4 ± 1min respectively for the DTF-VM, Microair and Aeroneb GO. Conclusion:Based on in vitro results, the DTF-VM nebulizer could be used as an aerosol generator to achieve rapidly high lung deposition, making it suitable for expensive biodrugs in development.
Studies of the control of plasma aldosterone concentration in normal man
Authors: Gordon H. Williams, John P. Cain, Robert G. Dluhy, Richard H. Underwood
Journal: Journal of Clinical Investigation (1972)

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.
Seroprevalence of IgG antibodies against Bordetella pertussis in healthy individuals aged 4–24 years in Turkey
Authors: M. Cevik, U. Beyazova, A.L. Aral, A. Duyan Camurdan, S. Ozkan, F. Sahin, C. Aybay
Journal: Clinical Microbiology and Infection (2008)

The distribution of IgG antibodies to Bordetella pertussis was investigated in serum samples from 550 subjects, aged 4–24 years, to determine the optimal age for booster immunisation. Levels of antibody to B. pertussis antigens were determined using an ELISA that measures a mixture of pertussis toxin, filamentous haemagglutinin and lipopolysaccharide. Geometric mean titres of anti-pertussis antibodies in subjects aged 4–6 years were significantly lower than those in other age groups, which reflects waning immunity following vaccination. High positive titres in older children and adolescents suggested acquired B. pertussis infection, and booster doses at the ages of 7 and 15 years are therefore suggested.
Risk and Timing of Neutropenic Events in Adult Cancer Patients Receiving Chemotherapy: The Results of a Prospective Nationwide Study of Oncology Practice
Authors: Jeffrey Crawford, David C. Dale, Nicole M. Kuderer, Eva Culakova, Marek S. Poniewierski, Debra Wolff, Gary H. Lyman
Journal: Journal of the National Comprehensive Cancer Network (2008)

This study was undertaken to describe the relationship between the occurrence and timing of neutropenic events and chemotherapy treatment in a community-based population of patients with cancer. The study included 2962 patients with breast, lung, colorectal, lymphoma, and ovarian cancers from a prospective U.S. registry of patients initiating a new chemotherapy regimen. Detailed patient-, disease-, and treatment-related data, including toxicities, were captured at baseline, the beginning of each cycle, and each midcycle blood draw for up to 4 cycles of treatment. Primary outcomes included febrile neutropenia (FN), severe neutropenia without fever/ infection, and relative dose intensity (RDI). Thirty-seven percent of patients were aged 65 years or older, 43.5% had an Eastern Cooperative Oncology Group performance status of 1 or greater, and 27% had 1 or more comorbidities. Reductions in RDI to less than 85% of standard in the first cycle were planned in 23.6% of patients, whereas primary colony-stimulating factor prophylaxis was used in 18.2%. In the first 3 cycles of treatment, 10.7% of patients experienced FN, with most of these events (58.9%) occurring in the first cycle. This first-cycle pattern was consistently observed despite wide variations in event rates by tumor type, disease stage, chemotherapy regimen and dose, and patient characteristics. Despite frequent planned reductions from standard RDI, the incidence of FN remains high in community oncology practice in the United States. Improved methods of pretreatment assessment of patient risk factors for neutropenia are needed.
Red Blood Cell Transfusion
Authors: Harvey G. Klein, Willy A. Flegel, Charles Natanson
Journal: JAMA (2015)

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Circulating Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Biomarker of Emphysema and the RAGE Axis in the Lung
Authors: John G. Yonchuk, Edwin K. Silverman, Russell P. Bowler, Alvar Agustí, David A. Lomas, Bruce E. Miller, Ruth Tal-Singer, Ruth J. Mayer
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD. One molecule that has attracted attention as a potentially useful biomarker specifically for the emphysema subpopulation is the soluble receptor for advanced glycation end products (sRAGE). As the soluble isoform of a key proinflammatory signaling receptor, sRAGE acts as a "decoy" for RAGE ligands and prevents their interaction with the receptor. Multiple reports have now linked sRAGE to COPD, and more specifically to emphysema, and evidence is accumulating that this link is likely mechanistic in nature. Here we review the current state of knowledge about sRAGE biology, the mechanistic links to COPD, and the evidence for using it as a biomarker for emphysema. We also discuss sRAGE as a potential target for therapeutic intervention in COPD.
Identification and Characterization of Hypoxia-Regulated Endothelial Circular RNA
Authors: Jes-Niels Boeckel, Nicolas Jaé, Andreas W. Heumüller, Wei Chen, Reinier A. Boon, Konstantinos Stellos, Andreas M. Zeiher, David John, Shizuka Uchida, Stefanie Dimmeler
Journal: Circulation Research (2015)

Circular RNAs (circRNAs) are noncoding RNAs generated by back splicing. Back splicing has been considered a rare event, but recent studies suggest that circRNAs are widely expressed. However, the expression, regulation, and function of circRNAs in vascular cells is still unknown.Here, we characterize the expression, regulation, and function of circRNAs in endothelial cells.Endothelial circRNAs were identified by computational analysis of ribo-minus RNA generated from human umbilical venous endothelial cells cultured under normoxic or hypoxic conditions. Selected circRNAs were biochemically characterized, and we found that the majority of them lacks polyadenylation, is resistant to RNase R digestion and localized to the cytoplasm. We further validated the hypoxia-induced circRNAs cZNF292, cAFF1, and cDENND4C, as well as the downregulated cTHSD1 by reverse transcription polymerase chain reaction in cultured endothelial cells. Cloning of cZNF292 validated the predicted back splicing of exon 4 to a new alternative exon 1A. Silencing of cZNF292 inhibited cZNF292 expression and reduced tube formation and spheroid sprouting of endothelial cells in vitro. The expression of pre-mRNA or mRNA of the host gene was not affected by silencing of cZNF292. No validated microRNA-binding sites for cZNF292 were detected in Argonaute high-throughput sequencing of RNA isolated by cross-linking and immunoprecipitation data sets, suggesting that cZNF292 does not act as a microRNA sponge.We show that the majority of the selected endothelial circRNAs fulfill all criteria of bona fide circRNAs. The circRNA cZNF292 exhibits proangiogenic activities in vitro. These data suggest that endothelial circRNAs are regulated by hypoxia and have biological functions.