tbuckley/cabot-search huggingface dataset:
Cancer Care Delivery Research and the National Cancer Institute SEER Program
Authors: Steven J. Katz
Journal: JAMA Oncology (2015)

Initiativestobuildbigdata to informand improvethequalityofcancercaredelivery in theUnitedStatesareevolvingrapidly.Advances in informationtechnologyhavemade it increasinglymore feasible toefficientlycollectclinicaldataacross facilitiesand institutionstoaddress challenges related to access, delivery, anddisparities in care. TheNational Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)programisuniquelypositionedintheUnitedStatesto leverage bigdatato informoncologypractice inthecommunity.Theparticipatingregional registriescompriseapopulationthat isdiverseandrepresentative of the United States. The registries have unique state data agreementsandhealthcarefacilitypartnerships(hospitalsandpathology laboratories) that enable them to collect uniformvalid clinical informationaboutthefirstcourseofcancertreatmentforvirtuallyallpatientswhoreceivediagnoses in their regionalcatchmentareas.These data have been used bymany hundreds of investigators to generate morethan8000scientificarticles thataddressburdenofcancer,diseaseetiologyandbehavior,disparities incancerhealthoutcomes,and quality of oncology care. But there are some important limitations to SEERdata. First, the levelofdetailabouttestsandtreatments is limited.Forexample, information about adjuvant chemotherapy regimens is not routinely collected. Second, thequality and completeness of the clinical data that arecollectedmayvarybycancerconditionandacross regions.Finally, informationrelatedtopatientsocioeconomicstatus is limited.Forexample, SEERdata currently includepatient-level information for race andmarital statusbut not for income, education, or insurance status. JAMA
cPAP compliance and survival in elderly and sleep apnoea patients
Authors: Rodrigo Alonso Moralejo, Salvador de la Torre Carazo, Trinidad Diaz Cambriles, Jesus Muñoz Mendez, Maria Josefa Diaz de Atauri, Angel Lopez Encuentra
Journal: European Respiratory Journal (2011)

Introduction: Sleep apnea-hypopnea syndrome (SAHS) prevalence increases with age, but very few data are available on this population.

Aim: To describe the clinical features, survival and tolerance to cPAP treatment of aged patients.

Methods: Observational, concurrently study performed during ten years including patients with SAHS evaluated in our Sleep Disorders Unit (SDU) at the age of 80 or older. Failure of treatment was defined when cPAP use was below 3.5 hours per day. Kaplan Meier and Log rank tests were performed for the survival analysis.

Results: 1.8% (144/7989) of patients were at least 80 years old when were studied in our SDU. There were 72 women (50%). The patients characteristics expressed by mean and standard deviation were, age: 82 (1.7), body mass index: 33 (4.3) Epworth test: 12.5 (5.3), neck circumference 41.2 (9). The 93% (135/144) of the patients were diagnosed of SAHS. 57% (83/144) of the patients started treatment with cPAP. 28/83 (34%) of them used it less than 3.5 hours. The survival analysis results are listed in the table beneath:

View this table:

Use of cPAP





Conclusion: Although the percentage of aged patients is low compared with the whole population, those who fulfil correct treatment with cPAP seem to have a longer survival in 10 years.
Beta-adrenergic blockers for the control of aggressive behaviors in patients with chronic schizophrenia
Authors: P J Sorgi, J J Ratey, S Polakoff
Journal: American Journal of Psychiatry (1986)

The authors conducted a chart review to determine the effect of beta blockers on chronic assaultiveness in seven patients with chronic schizophrenia. Six of the patients showed improvement. Four of the seven showed a greater than 70% decrease in actual assaults.
Metformin-associated lactic acidosis: Current perspectives on causes and risk
Authors: Ralph DeFronzo, G Alexander Fleming, Kim Chen, Thomas A Bicsak
Journal: Metabolism (2015)

Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (<10 cases per 100,000 patient-years). Several groups have suggested that current renal function cutoffs for metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.
High dose methylprednisolone counteracts the negative effect of rocuronium on diaphragm function in a rat model of mechanical ventilation
Authors: Karen Maes, Dries Testelmans, Debby Thomas, Marc Decramer, Ghislaine Gayan-Ramirez
Journal: European Respiratory Journal (2011)

Rationale:  We previously showed that rocuronium (ROC) combined with 24h of controlled mechanical ventilation leads to an additional negative effect on diaphragm function in rats. Based on clinical observations we hypothesized that the combination of rocuronium with corticosteroids in our animal model of CMV would result into a further deterioration of diaphragm function.   Methods:  Mechanically ventilated (24h) rats received intravenously either a continuous infusion of saline (CMV) or ROC or ROC combined with an intramuscular injection of 80 mg/kg of methylprednisolone (ROC-MP).   Results:  ROC treatment resulted in a significant reduction of diaphragm force compared with CMV. Treatment with MP attenuated the ROC-induced contractile dysfunction of the diaphragm. Cross-sectional area of the diaphragm type IIx/b fibres tended to decrease with 13% after ROC compared with the other groups. Diaphragm MURF-1 mRNA expression was significantly increased with 30% after ROC and ROC-MP compared to CMV while MAFbx was similar in all groups. Diaphragm caspase-3 activity (+ 39%) and calpain activity (+99%) were increased after ROC compared to CMV. Treatment with MP abolished the increase in caspase-3 and calpain activity. Proteolytic activity in the gastrocnemius was similar in all groups. The ratio of MyHC to actin was similar in the diaphragm and the gastrocnemius in all groups.   Conclusions:  The additional negative effect of ROC on the diaphragm during CMV is abolished with administration of a high dose of MP. This effect is most likely due to an inhibition of the calpain and caspase-3 system.  Funded by: FWO-Vlaanderen G.0197.07 and AstraPharmaceuticals
Human Kidney Tubules Detoxify Chloroacetaldehyde, a Presumed Nephrotoxic Metabolite of Ifosfamide
Authors: LAURENCE DUBOURG, CHRISTIAN MICHOUDET, PIERRE COCHAT, GABRIEL BAVEREL
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The nephrotoxic effects of the antineoplastic drug ifosfamide have been attributed to its hepatic metabolite chloroacetaldehyde. The effects of chloroacetaldehyde on isolated human kidney cortex tubules metabolizing lactate (a physiologic substrate in human kidneys) were investigated. At concentrations of ≥0.5 mM, chloroacetaldehyde was toxic to the human kidney tubules, as demonstrated by a dramatic decrease in cellular ATP levels and a large increase in lactate dehydrogenase release; chloroacetaldehyde also stimulated pyruvate accumulation and inhibited lactate removal and glucose synthesis. These effects, which were associated with incomplete disappearance of chloroacetaldehyde and extensive depletion of the cellular CoA, acetyl-CoA, and glutathione contents, were prevented by the addition of thiol-protecting drugs (mesna and amifostine). Human kidney tubules were demonstrated to metabolize chloroacetaldehyde at high rates, presumably via aldehyde dehydrogenase, which is very active in human kidneys. Carbon-13 nuclear magnetic resonance spectroscopy measurements indicated that human kidney tubules converted [2- 13 C]chloroacetaldehyde to [2- 13 C]chloroacetate, the further metabolism of which was very limited. At equimolar concentrations, chloroacetate was much less toxic than chloroacetaldehyde, indicating that chloroacetate synthesis from chloroacetaldehyde by human kidney tubules represents a detoxification mechanism that could play a role in vivo in preventing or limiting the nephrotoxic effects observed during ifosfamide therapy.
Impact of diabetes mellitus on treatment outcomes of patients with active tuberculosis in an endemic area
Authors: Adriana Socaci, Gheorghe Nini, Constantin Marica
Journal: European Respiratory Journal (2013)

Introduction. Diabetes mellitus (DM) is an emerging chronic health condition of developed and developing countries. Due to the association between diabetes and pulmonary tuberculosis (TB), diabetes may threaten the control of TB. Aims. We conducted a study to determine the prevalence of DM among TB patients, and to determine and compare treatment outcomes among TB patients with versus without DM. Methods. A retrospective cohort study included all patients with culture-confirmed TB diagnosed in 2010 and 2011, in west of the country. Results. Of 228 TB patients, 42 (18.4%) had DM. Patients with diabetes had 2.0 times higher odds of death than patients without diabetes (p = 0.18). Of the diabetic TB patients, 9.5% died within one month after starting TB treatment, compared with 3.5% of patients without diabetes (p = 0.09) Time to sputum culture conversion was longer in patients with diabetes than patients without diabetes (median 49 versus 39 days, p = 0.09). Two-month culture conversion proportions were similar (69% and 70%). There was no difference in the proportion of patients with baseline drug resistance, comparing patients with diabetes to patients without diabetes (14.3% versus 15.3%, p = 0.87). Treatment failure occurred in 4.1% of patients without diabetes and 6.7% of patients with diabetes (p = 0.51). Conclusions. In our TB patient population, DM was a risk factor for death, and it had a negative impact on treatment outcome. Enhanced medical vigilance, especially during the early part of TB treatment, is warranted.
Abstract 1987: The site of Thin-cap Fibroatheroma in Native Coronary Arteries: A Three-Vessel Optical Coherence Tomography Study
Authors: Kenichi Fujii, Motomaru Masutani, Takahiro Okumura, Daizo Kawasaki, Takafumi Akagami, Tsuyoshi Sakoda, Tohru Masuyama, Mitsumasa Ohyanagi
Journal: Circulation (2007)

Background: Plaque rupture is the most frequent cause of coronary thrombosis such as acute myocardial infarction (AMI). It has been recognized that thin-cap fibroatheroma (TCFA) is the precursor lesion of plaque rupture. It is clinically important to understand the potential sites of TCFA. Therefore, we evaluated the geographic distribution of TCFAs using optical coherence tomography (OCT) that is a high-resolution (approximately 10 μm) imaging modality. Methods: We performed three-vessel OCT examinations in 51 patients; 34 AMI and 17 stable angina pectoris (SAP) patients. OCT criteria for TCFA was lipid-rich plaque with cap thickness &lt;65 μm. The distance between each TCFA segment and the respective coronary ostium was measured with motorized OCT transducer pullback. The overall length of the region of interest, subsequently divided into 10mm segments, was 68.2 ± 27.1 mm long (range: 18.9 – 121.1 mm). Results: The OCT detected 86 TCFAs in 41 patients: 32 were identified in AMI patients and 9 in SAP patients. Of all TCFAs, 26 were located in the left anterior descending artery (LAD), 16 in the left circumflex artery (LCX), and 44 in the right coronary artery (RCA). Most LAD TCFAs were located between 0 and 40mm from the LAD ostium (96%). Similarly, LCX TCFAs were predominantly located between 0 and 40mm from the LCX ostium (69%). Conversely, RCA TCFAs were evenly distributed in the entire coronary trees. The clustering of the TCFAs was similar in culprit segments compared with non-culprit segments. Conclusion: Three-vessel OCT imaging showed that TCFAs tend to cluster in predictable “hot spots” within the proximal segments of the LAD and LCX, and the entire segments of the RCA.
Multiplicity of Cell Response to the BAI Strain A (Myeloblastosis) Avian Tumor Virus. II. Nephroblastoma (Wilms' Tumor): Ultrastructure&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Ursula Heine, Hideo Ishiguro, J. R. Sommer, Dorothy Beard, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1962)

The ultrastructural features of the cells comprising the nephronic, mesenchymal, and chondral tissues of the avian nephroblastoma induced by the BAI strain A (myeloblastosis virus) have been studied. The findings support the interpretations of histologic examinations that the tumor arises by a series of parallel and discontinuous processes of growth and differentiation of primitive nephrogenic cells residual in the postembryonic kidney. No evidence was seen of genetic transformation; instead, particularly with the nephronic elements, differentiation was a manifestation of potentials inherent in the cells of origin. Virus and processes of virus synthesis were found in association with the cellular elements of all component tissues of the tumor. Virus elaboration and release from all cell types occurred alike, but in different degrees, by the budding of the cytoplasmic membrane. In the cartilage were virus particles apparently containing fibrils formed simultaneously by the membrane of the chondrocytes.
The Noscapine Chronicle: A Pharmaco‐Historic Biography of the Opiate Alkaloid Family and its Clinical Applications
Authors: Padmashree C. G. Rida, Dillon LiVecche, Angela Ogden, Jun Zhou, Ritu Aneja
Journal: Medicinal Research Reviews (2015)

Abstract Given its manifold potential therapeutic applications and amenability to modification, noscapine is a veritable “Renaissance drug” worthy of commemoration. Perhaps the only facet of noscapine's profile more astounding than its versatility is its virtual lack of side effects and addictive properties, which distinguishes it from other denizens of Papaver somniferum . This review intimately chronicles the rich intellectual and pharmacological history behind the noscapine family of compounds, the length of whose arms was revealed over decades of patient scholarship and experimentation. We discuss the intriguing story of this family of nontoxic alkaloids, from noscapine's purification from opium at the turn of the 19th century in Paris to the recent torrent of rationally designed analogs with tremendous anticancer potential. In between, noscapine's unique pharmacology; impact on cellular signaling pathways, the mitotic spindle, and centrosome clustering; use as an antimalarial drug and cough suppressant; and exceptional potential as a treatment for polycystic ovarian syndrome, strokes, and diverse malignancies are catalogued. Seminal experiments involving some of its more promising analogs, such as amino‐noscapine, 9‐nitronoscapine, 9‐bromonoscapine, and reduced bromonoscapine, are also detailed. Finally, the bright future of these oftentimes even more exceptional derivatives is described, rounding out a portrait of a truly remarkable family of compounds.
Abstract 13867: A Tissue Engineered Chondrocyte Cell-Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy
Authors: Yasuhiro Shudo, Jeffrey E Cohen, Alen Trubelja, Matthew Ku, John W MacArthur, Jay B Patel, Alexander S Fairman, Bryan B Edwards, Christopher Brusalis, Pavan Atluri, Arudo Hiraoka, Shigeru Miyagawa, Yoshiki Sawa, Y. J Woo
Journal: Circulation (2013)

Introduction:  There exists a substantial body of work describing cardiac support devices to mechanically support the left ventricle (LV); however, these devices lack biological effects. To remedy this, we implemented a cell-sheet engineering approach utilizing chondrocytes, which in their natural environment produce a relatively elastic extracellular matrix (ECM) for a cushioning effect. Therefore, we hypothesized that a chondrocyte cell-sheet applied to infarcted and borderzone myocardium will biologically enhance the ventricular ECM and increase elasticity to augment cardiac function in a model of ischemic cardiomyopathy (ICM).   Methods and Results:  Primary articular cartilage chondrocytes of Wistar rats were isolated and cultured on temperature-responsive culture dishes to generate cell-sheets. A rodent ICM model was created by ligating the left anterior descending coronary artery. Rats were divided into two groups: cell-sheet transplantation and no treatment. The cell-sheet was placed onto the surface of the heart covering the infarct and borderzone areas. At 4 weeks following treatment, the decreased fibrotic extension and increased elastic microfiber networks in the infarct and borderzone areas correlate with this technology’s potential to stimulate ECM formation. The enhanced ventricular elasticity was further confirmed by the axial stretch test, which revealed that the cell-sheet significantly attenuated tensile modulus, a parameter of stiffness. This translated to increased wall thickness in the infarct area, decreased LV volume, and the improvement of LV function as indicated by echocardiography and pressure-volume analyses. (Table)   Conclusions:  The chondrocyte cell-sheet strengthens the ventricular biomechanical properties by inducing the formation of elastic microfiber networks in ICM, resulting in attenuated myocardial stiffness and improved myocardial function.
Expression of HLA-DR in circulating polymorphonuclear neutrophils of COPD patients
Authors: Sergio Scrimini, Jaume Pons, Borja Cosío, Alvar Agusti, Andreas Jahn, Rocío Córdova, Jaume Sauleda
Journal: European Respiratory Journal (2013)

Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by an abnormal inflammatory response of the lungs to noxious particles or gases where both innate and adaptive immunity participate. Polymorphonuclear neutrophils (PMNs) play a key role in the pathogenesis of COPD due to the production of reactive oxygen species and lytic enzymes. Recent evidence shows that PMNs can express MHC class II and activate an adaptive immune response.  Material and methods: The expression of HLA-DR (MHC class II) and CD 11b, as a marker of activation, were quantified on peripheral PMNs by flow cytometry in: a) 31 non-smokers controls (NSC) (mean±SD, 60 ±8y., FEV1% pred= 112 ± 14,6); b) 34 smokers with normal lung function (SM) (57±9y., FEV1% pred= 102±16, 30±18 paq/y); and c) 53 COPD patients (64±10y, FEV1% pred=61±20, 54±30 paq/y).  Results: The percentage of HLA-DR+PMNs was higher in COPD patients (median [range]: 12.7[1.7-78.3%]) than in NSC (7.6 [1.7-23.8], p=0.003). COPD current smokers showed an increased proportion of HLA-DR+PMNs (14.7 [3.7-78.3]) as compared with current smokers with normal spirometry (10 [2.4-20.6], p=0.02) and COPD former smokers (11.2 [1.7-23.2], p=0.009). The correlation between the expression of CD 11b and HLA-DR was significant (r=0.785, p=  Conclusions: The HLA-DR expression on circulating PMNs of COPD patients suggests the participation of activated PMNs in the modulation of the adaptive immune response in COPD.
IL-17a expression in transbronchial biopsy samples in sarcoidosis
Authors: Nurdan Köktürk, Nalan Akyürek, Muge Aydogdu, Ayse Baha, Haluk Türktas
Journal: European Respiratory Journal (2012)

Background: Th17 is a new subset of CD4(+) T cell population and characterized by the release of cytokines such as IL-17A, IL-17F and IL-22. Multiple studies in humans and animals have described the role of Th17 cells in the pathogenesis of several autoimmune and chronic inflammatory diseases such as psoriasis, inflammatory bowel diseases, tuberculosis and lung fibrosis.

Aim:To determine the possible role of Th17 cells in the pathogenesis of sarcoidosis by evaluating the IL-17A levels in lung biopsy samples of sarcoidosis patients.

Method: IL-17A expression was evaluated with immunohistochemical analysis. The area that had higher IL-17A antibody positivity was evaluated with x40 magnification and the positive staining inflammatory cells (macrophage and lymphocyte) were counted.

Results: A total of 41 sarcoidosis patients [32(78%) female] with the mean age of 48 years were included in the study. Among them 22(54%) were diagnosed as Stage 1,17(42%) as Stage 2,1(%2) as Stage 3 and 4 sarcoidosis.In the whole study group only 2 (5%) patients had no IL-17A(+) inflammatory cells. In the remaining, 9(22%) patients had one IL17A(+) staining cell, 15(37%) had 2 cells, 5 (12%) had 3 cells, 9 (22%) had 4 cells and 1(2%) had 5 cells. The IL-17A (+) staining cells were identified at the periphery of the granuloma. No statistically significant correlation was identified between the number of IL17A(+) staining inflammatory cells and plasma ACE levels, CD4/CD8 ratio and the stage of the disease (p> 0.05).

Conclusion: The identification of IL17A (+) staining inflammatory cells in the periphery of the sarcoidosis granulomas, may indicate that Th17 cells have an important role in the pathognesis of sarcoidosis.