tbuckley/cabot-search huggingface dataset:
ACC 2015 Core Cardiovascular Training Statement (COCATS 4) (Revision of COCATS 3)
Authors: Jonathan L. Halperin, Eric S. Williams, Valentin Fuster, Valentin Fuster, Jonathan L. Halperin, Eric S. Williams, Nancy R. Cho, William F. Iobst, Debabrata Mukherjee, Prashant Vaishnava, Sidney C. Smith, Vera Bittner, J. Michael Gaziano, John C. Giacomini, Quinn R. Pack, Donna M. Polk, Neil J. Stone, Stanley Wang, Gary J. Balady, Vincent J. Bufalino, Martha Gulati, Jeffrey T. Kuvin, Lisa A. Mendes, Joseph L. Schuller, Jagat Narula, Y.S. Chandrashekhar, Vasken Dilsizian, Mario J. Garcia, Christopher M. Kramer, Shaista Malik, Thomas Ryan, Soma Sen, Joseph C. Wu, Thomas Ryan, Kathryn Berlacher, Jonathan R. Lindner, Sunil V. Mankad, Geoffrey A. Rose, Andrew Wang, Vasken Dilsizian, James A. Arrighi, Rose S. Cohen, Todd D. Miller, Allen J. Solomon, James E. Udelson, Mario J. Garcia, Ron Blankstein, Matthew J. Budoff, John M. Dent, Douglas E. Drachman, John R. Lesser, Maleah Grover-McKay, Jeffrey M. Schussler, Szilard Voros, L. Samuel Wann, Christopher M. Kramer, W. Gregory Hundley, Raymond Y. Kwong, Matthew W. Martinez, Subha V. Raman, R. Parker Ward, Mark A. Creager, Heather L. Gornik, Bruce H. Gray, Naomi M. Hamburg, William F. Iobst, Emile R. Mohler, Christopher J. White, Spencer B. King, Joseph D. Babb, Eric R. Bates, Michael H. Crawford, George D. Dangas, Michele D. Voeltz, Christopher J. White, Hugh Calkins, Eric H. Awtry, Thomas Jared Bunch, Sanjay Kaul, John M. Miller, Usha B. Tedrow, Mariell Jessup, Reza Ardehali, Marvin A. Konstam, Bruno V. Manno, Michael A. Mathier, John A. McPherson, Nancy K. Sweitzer, Patrick T. O’Gara, Jesse E. Adams, Mark H. Drazner, Julia H. Indik, Ajay J. Kirtane, Kyle W. Klarich, L. Kristen Newby, Benjamin M. Scirica, Thoralf M. Sundt, Carole A. Warnes, Ami B. Bhatt, Curt J. Daniels, Linda D. Gillam, Karen K. Stout, Robert A. Harrington, Ana Barac, John E. Brush,, Joseph A. Hill, Harlan M. Krumholz, Michael S. Lauer, Chittur A. Sivaram, Mark B. Taubman, Jeffrey L. Williams
Journal: Journal of the American College of Cardiology (2015)
Abstract 2693: Mitral E/E’ underestimates Pulmonary Capillary Wedge Pressure During Exercise.
Authors: Sébastien Marchandise, Anne-Marie D’Hondt, Olivier Gurne, David Vancraeynest, Bernhard Gerber, Jean Louis Vanoverschelde, Agnes Pasquet
Journal: Circulation (2007)

Background. Previous studies have shown that resting LV filling pressures can be estimated noninvasively by use of the ratio of the early diastolic transmitral filling velocity (E) to the early diastolic septal tissue velocity (E’). Yet, limited data exist regarding the accuracy of this measurement during exercise. In this study, we therefore sought to evaluate the possible value of exercise E/E’ for predicting invasively measured pulmonary capillary wedge pressure (PCWP). Methods. 22 patients (57 ± 15 years, 10 males) with heart failure (n=14), valve disease (n=6) or pulmonary hypertension (n=2) underwent right heart catheterization during symptom limited bicycle exercise. For each patient, PCWP and Doppler measurements of E/E’ were acquired in left lateral decubitus, after 5 min of sitting and during the last minute of each exercise stage. Results. With exercise, heart rate increased from 78 ± 17 bpm to 118 ± 21 bpm, as did systolic blood pressure (from 128 ± 29 to 169 ± 30 mmHg, p&lt;0.001), PCWP (from 15 ± 6 to 24 ± 9 mmHg, p&lt;0.001), E velocity (from 84 ± 34 to 111 ± 41 cm.s -1 p&lt;0.001) and septal E’ (from 6.2 ± 2.7 to 9.0 ± 4.3 cm.s -1 p&lt;0.01). At rest, in both recumbent and sitting positions, E/E’ correlated well with PCWP (solid circle, y = 0.7856 X + 4.2084, r = 0.72). During exercise, E/E’ also correlated with PCWP (open circle, y = 0.5253x + 1.7168, r = 0.64). The relationship was nonetheless shifted downward and to the right compared to rest. Conclusion. While E/E’ correlates with PCPW both at rest and during exercise, the relationship between these 2 parameters is different under these 2 conditions. Therefore, E/E’ values defining elevated LV filling pressures at rest cannot be used during exercise.
Brain-selective mTOR inhibitors as potential therapeutics for glioblastoma multiforme
Authors: Rose M. Sheridan, Matthew A. Gregory, Hrvoje Petkovic, Sabine Gaisser, Rachel E. Lill, Michael J. Ward, Andrew L. Kaja, Christoph H. Beckman, Iain R. Challis, Steven J. Moss, Barrie Wilkinson, Peter Houghton, Ming-Qiang Zhang
Journal: Cancer Research (2006)

4485   Glioblastoma multiforme (GBM) is one of the most common primary CNS tumors and remains essentially universally fatal despite aggressive therapy. Many GBM cells have loss of PTEN function which confers increased activity of PI3K/Akt pathway. This in turn activates the mTOR, thereby increasing translation of a number of key proteins required for cell cycle progression. PTEN-deficiency in GBM has been associated with the poor prognosis of the disease. Inhibition of mTOR resulting in cell cycle arrest and apoptosis is therefore a rational approach for the development of novel anticancer therapeutics for this devastating disease. Three analogues of rapamycin, CCI-779, RAD001 and AP23573 are currently in clinical trials as potential anticancer agents. These rapamycin analogues are structurally very close to rapamycin with only a single ester or ether substitution at the C40 hydroxyl, and thus share many biological similarities to rapamycin, including some poor metabolic stability and pharmacokinetic drawbacks. A recent publication of CCI-779 Phase II study in patients with recurrent GBM suggests the agent is not effective, probably due to its poor penetration into the central nervous system (CNS) ( Investigational New Drugs  23, 357–361, 2005). We report here a series of novel rapamycin analogues generated by genetically engineered biosynthesis with significantly improved pharmaceutical properties as well as potent anticancer activities. Among this structurally diverse set of rapamycin analogues, we have identified compounds that have up to 4-fold increased water solubility, >100-fold increased Caco-2 permeability, 30-fold reduced efflux ratio and significantly increased metabolic stability over rapamycin. For example, BC210 has low nanomolar inhibitory potency against mTOR and exhibits potent anticancer activities in various  in vitro  and  in vivo  assays. It is not a substrate of P-gp and has a good oral bioavailability. Of particular importance is the effective penetration of the blood-brain barrier by BC210. When given i.v. 3 mg/kg in mice, it ‘accumulates’ in the brain resulting in the brain to blood ratio of 1.6 which is unique among all known rapamycin analogues. This unique pharmacokinetic property of BC210 makes the compound a highly promising candidate as a potential therapeutic for the treatment of GBM, either alone or in combination with other anticancer therapeutics. Structure-activity relationship, pharmacological characterisation and  in vivo  evaluation in an orthotopic  in vivo  GBM model of this series of novel mTOR inhibitors will be discussed.
New Appliances
Authors: I C KNIGHT
Journal: BMJ (1964)

rhodanase to the relatively non-toxic thio- cyanate (a process which is speeded up by the intravenous administration of sodium thiosulphate after intravenous nitrite), sub- lethal intoxications will recover in time spontaneously, and recovery will be aided by administration of oxygen and artificial respiration if natural respirations are weak or showing signs of failing.Further informa- tion may be obtained from reference books.
Abstract 1538: Acute Cardiac Effects of Marathon Running: Evidence of Right-Heart Overload
Authors: Justin E Trivax, Barry A Franklin, James A Goldstein, Kavitha M Chinnaiyan, Michael J Gallagher, Adam T dejong, James M Colar, David E Haines, Peter A McCullough
Journal: Circulation (2009)

Background. Cardiac dysfunction and elevated blood markers of myocardial injury have been reported after prolonged strenuous exercise. We sought to clarify the significance of these responses in he...
Abstract 4176: Quantification of Myocardial Blood Flow Reserve by 1st-Pass CT Imaging
Authors: Timothy Christian, George Gentchos, Bina Ahmed, Mei Lee Frankish, Stephen Bell, Michael Jerosch-Herold
Journal: Circulation (2008)

The accurate assessment of myocardial blood flow (MBF) is a potential adjunct to the anatomy of CT coronary angiography. To compare quantitative parameters from 1st-pass CT (FP CT) imaging with absolute measures of MBF in an animal model of altered MBF. A pig model of intracoronary adenosine (n=9) was used during FP CT. This produces a zone with hyperemic MBF and a control zone within a slice. Fluorescent microspheres (Mcsp) were injected into the left atrium with to determine absolute MBF concurrent with CT imaging. Pigs were placed in a 64-slice (Philips) CT with acquisition performed during IC adenosine. A 40% dilution of Iopamidol 370 (1ml/Kg) was injected IV at 5ml/sec. CT acquisition was ECG gated over 40 cardiac phases with the following parameters: 180° axial mode (pitch=0), field of view=250mmsq, 512×512 matrix, slice thickness=2.5 mm × 10 slices, temporal resolution=210ms, 120KV, 495ma. Mcsp were injected immediately following CT imaging. The heart was sectioned into 2.5mm slices to match the CT images and segmented. Time intensity curves (TIC) were generated from CT in adenosine and control zones based on Mcsp values. Mcsp coronary flow reserve (CFR) = hyperemic/control MBF, and CT CFR was derived from hyperemic/control area under curve from baseline corrected TIC (Klocke, Circ. 2001). MBF control=0.65±0.25, MBF adenosine=2.6±0.7 ml/min/g (p&lt;0.0001). CFR=4.5±1.05, CT CFR=4.4±1.5 (p=NS). There was a significant (r=0.93, p&lt;0.0001) correlation between CFR and CT CFR (figure ). FP CT myocardial perfusion imaging is feasible at clinically relevant radiation dosimetry and provides reasonable estimates of CFR during hyperemia.
Accuracy of sentinel lymph node (SLN) biopsy after neoadjuvant chemotherapy (NC) for breast cancer.
Authors: J. M. Jurado, I. Blancas, F. J. Gómez, I. Zarcos, M. Delgado, J. Carrillo, M. Legeren, B. Rios, M. J. Sánchez, J. L. García-Puche
Journal: Journal of Clinical Oncology (2010)

e11029 Background: Sentinel lymph node (SLN) biopsy has proved to be an accurate method for detecting nodal metastases in previously untreated patients with early-stage breast cancer. We investigated the accuracy of this technique for patients with more advanced breast cancer after neoadjuvant chemotherapy (NC). Methods: Patients with stage II or III breast cancer who had undergone NC before breast surgery were eligible for this prospective study. Trastuzumab was administered with NC if HER2 was overexpressed. All patients were offered axillary lymph node dissection. Negative sentinel and axillary nodes were subjected to additional processing with serial step sectioning and immunohistochemical staining with an anticytokeratin antibody to detect micrometastases. Results: From January 2007 to December 2009, 51 patients enrolled from Hospital Clínico of Granada were found suitable for evaluation. Forty-five percent had T3-T4 tumors, 68% were clinically node positive and 21% overexpressed HER2. Eighty-eight percent received taxanes in addition to doxorubicin based NC. The detection rate was 92% (47 of 51 patients), and the false-negative rate (the sentinel node was negative, but at least one nonsentinel node contained metastases) was 0.2% (one of 48 patients). Patients without axillary palpable nodes (N0) before NC had not different significant false-negative rate compared with patients with axillary suspicious nodes (N1) (100% vs 96%; p = 0.23). Fifteen (31.9%) of the 47 successfully mapped patients had positive SLNs, and in nine of those 15 patients (60%), the SLN was the only positive node. Additional processing revealed occult micrometastases in two patients (one in sentinel node and one in a nonsentinel node). Conclusions: This study confirms the feasibility and accuracy of SLN biopsy after NC in the case of advanced breast cancer. False-negative findings occurred at a low rate throughout the series. This technique is a way to guide the axillary treatment of patients who are clinically node negative after neoadjuvant chemotherapy. No significant financial relationships to disclose.
Une épidémie de gastro-entérite à virus Norwalk-like chez des touristes visitant Andorre, en janvier–février 2002
Authors: B Pedalino, E Feely, P McKeown, B Foley, B Smyth, A Moren
Journal: Eurosurveillance (2003)

Une etude retrospective de cohorte a ete menee pour investiguer une epidemie de gastro-enterite a virus Norwalk-like chez des vacanciers irlandais ayant sejourne en Andorre, en janvier–fevrier 2002. Les resultats montrent que l’exposition au risque etait
Solid lipid microparticles: An approach for improving oral bioavailability of aspirin
Authors: T.H. Gugu, S.A. Chime, A.A. Attama
Journal: Asian Journal of Pharmaceutical Sciences (2015)

The objectives of the work were to develop a lipid based delivery system for aspirin and to evaluate its physicochemical and pharmacodynamic properties. Aspirin-loaded solid lipid microparticles (SLMs) were formulated by hot homogenization and analysed for their encapsulation efficiency (EE%), in vitro release, particle size, anti-inflammatory and ulcer inhibition properties. Particle size ranged from 33.10 ± 5.85 to 43.50 ± 7.27 µm for batches A1 to A3 SLMs loaded with 1, 3 and 5% aspirin and containing Poloxamer 407, while batches B1, B2 and B3 formulated with Soluplus as surfactant had particle size range of 31.10 ± 1.46 to 45.60 ± 2.92 µm. Batches A1 and B1 containing 1% of aspirin had the highest EE of 70 and 72% respectively. Maximum in vitro release of 95.1 and 93.2% were obtained at 8 h from batches A1 and B1 respectively. SLMs exhibited about 77.8% oedema inhibition, while the reference had 66.7% and ulcer inhibition range of 25–75%. Aspirin-loaded SLMs exhibited good properties and could be used orally twice daily for the treatment of inflammation.
Abstract 8381: Safety and Effect of Adipose Tissue Derived Stem Cell Implantation in Patients with Critical Limb Ischemia
Authors: Han Cheol Lee, Sung Gyu An, Hye Won Lee, Mi Jin Yang, Jun Hyuk Oh, Jung Hyun Choi, Kwang Soo Cha, Taek Jong Hong
Journal: Circulation (2011)

Adipose tissue-derived mesenchymal stem cells (ADSCs) are potent and effective for inducing regeneration of damaged tissue. Treatment of critical limb ischemia (CLI) is occasionally difficult through bypass operation or percutaneous vascular intervention. ADSC transplantation shows proangiogenic action in animal hindlimb ischemia models. We performed multiple intramuscular ADSC injections in CLI patients to treat diabetic foot and thromboangiitis obliterans (TAO) and assessed its safety and efficacy. The study included 15 CLI patients (15 men, median age: 52 years, range: 24-73 years) with ischemic resting pain in one limb with/without nonhealing ulcers and necrotic foot (Rutherford class II-4: n = 3, III-5: n = 9, III-6: n = 3) who did not undergo nonsurgical or surgical revascularization. ADSCs were isolated from adipose tissue of TAO patients (B-ADSCs), diabetes patients (D-ADSCs), and healthy donors (control ADSCs) by using 0.075% collagenase digestion. In a colony forming unit (CFU) assay using stromal vascular fraction, B-ADSCs and D-ADSCs yielded lesser colonies than normal ADSCs. However, culture-expanded B-ADSCs showed normal proliferation ability compared to control ADSCs. Adipogenic and osteogenic differentiation potential did not differ between B-ADSCs and control ADSCs. Culture-expanded D-ADSCs showed lower proliferation ability and osteogenic differentiation and higher adipogenic differentiation than control ADSCs. Multiple intramuscular ADSC injections cause no complications during the follow-up period (mean follow-up time: 6 months). Clinical improvement occurred in 66.7% of patients. Five patients required minor amputation during follow-up. All amputation sites healed completely. At 6 months, significant improvement was noted on pain rating scales and in claudication walking distance. Digital subtraction angiography (DSA) before and 6 months after ADSC implantation showed formation of numerous vascular collateral networks across affected arteries. Multiple intramuscular ADSC injections may be a safe alternative to achieve therapeutic angiogenesis in patients with CLI who are refractory to other treatment modalities
Are based on Christian ethics
Authors: P A Wilkinson, M. Houghton
Journal: BMJ (1994)

EDITOR,—It is encouraging to see the profession discussing its core values, with the lead given by the chief medical officer1 and the summit meeting reported by Richard Smith.2 Coincidentally, the Sheffield group of the Christian Medical Fellowship held a day conference in the midlands on 5 November to discuss “foundations and the future.” Many of the …
Hidden abnormalities and novel disease-related genomic changes during development of esophageal adenocarcinomas
Authors: Tadayuki Akagi, Tetsuo Ito, Yulan Cheng, Takatsugu Kan, Motohiro Kato, Go Yamamoto, Norihiko Kawamata, Carl Miller, Zhe Jin, Seishi Ogawa, Stephen Meltzer, H. Phillip Koeffler
Journal: Cancer Research (2008)

907   Barrett’s esophagus (BE) is a metaplastic condition caused by chronic gastro-esophageal reflux and believed to represent an early step in the development of esophageal adenocarcinoma (EAC). Single-nucleotide polymorphism microarray (SNP-chip) analysis is a novel approach to examining genomic changes, including copy-number gains or losses, as well as, loss of heterozygosity (LOH) with normal copy number (uniparental disomy or UPD). Using 250K SNP-chips, we examined the neoplastic progression of BE to EAC, initially by studying 6 matched sample sets ( i.e.,  including normal esophagus [NE], BE and EAC). Three sets revealed no detectable genetic changes in BE or EAC  vs.  NE. In contrast, the remaining 3 sets showed striking abnormalities. Two EACs exhibited several amplifications involving the ERBB2, CSF3, RARA and TOP2A genes, while 1 EAC manifested amplification of CTGF and c-Myb. None of these amplifications were detected in BE.  Next, we expanded our analysis to include 5 additional matched NE-BE pairs and 1 additional matched NE-EAC pair (in total, 11 BE and 7 EAC samples). Seven (64%) of 11 BE samples and 4 (57%) of 7 EAC samples exhibited one or more genomic abnormalities, including deletions, duplications, amplifications and UPD. Several abnormalities common to more than one tissue sample were identified, including chromosome 9p UPD (32.7 Mb, 2 BE samples [18%]), 9p deletion (31.7 Mb, 2 BE samples [18%]), deletion of CDKN2A (3 BE samples [27%]), and amplification of 17q12-q21.1 (3.5 Mb, 2 EAC samples [29%]). Interestingly, one BE sample contained a homozygous deletion at 9p22.3-22.2 (1.2 Mb): this region harbors only one known gene, basonuclin 2 (BNC2). Real-time PCR analysis confirmed decreased expression of BNC2 mRNA in the BE sample, but not in the matched NE control. Furthermore, BNC2 was found to be methylated in the EAC-derived cell line OE33, and transfection and stable expression of BNC2 caused growth arrest of OE33 cells. Taken together, these findings suggest that BNC2 functions as a tumor suppressor gene in the esophagus, and that silencing of this gene occurs during the development of EAC. Moreover, to our knowledge, this work reveals for the first time exciting hidden abnormalities and novel cancer-related genomic regions in BE and EAC.
Folate-hapten conjugate targeted immunotherapeutics: pharmacokinetics, biodistribution, and enhanced antitumor activity.
Authors: Yingjuan Lu, Le-Cun Xu, Nikki Parker, Elaine Westrick, Marilynn Vetzel, Philip S. Low, Christopher P. Leamon
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5574 

One class of emerging investigational therapies for cancer treatment has involved the mobilization of the immune system to first recognize and then attack the malignancy. The broad distribution of folate receptor (FR) expression among human neoplasms, along with its pronounced over-expression in malignant tissues and extremely limited distribution among normal epithelium, suggests an exciting potential for a FR-based immunotherapy against epithelial cancers. We have developed an immunotherapy strategy that utilizes a small folate-hapten conjugate (folate-FITC) to redirect endogenously produced anti-hapten antibody to FR-positive tumor cells. In an effort to optimize the therapeutic folate-FITC dosing regimen, pharmacokinetic studies were performed by administering radiolabeled folate-FITC to both tumor- and non-tumor bearing mice that were either naive or FITC-immunized. We found that the folate-FITC conjugate itself displays moderate nonspecific binding to serum proteins, and it is not significantly distributed to erythrocytes. In naive (non-immunized) mice, folate-FITC eliminates quickly through the liver and kidneys; but, in immunized mice, folate-FITC forms immune complexes with FITC-specific antibodies which in turn decreases its plasma clearance rate. The degree of anti-FITC antibody occupancy by circulating folate-FITC (i.e. the immune complex formation) was detectable ex-vivo by ELISA analysis using folate binding protein-coated plates. Here, we learned that excessive folate-FITC dosing simultaneously leads to (i) the saturation of circulating FITC-specific antibodies, and (ii) saturation of the tumor-associated FRs. Under these dosing conditions, “anchoring” of anti-FITC antibody to the FR-positive tumor cells is compromised. Folate-FITC exhibited a linear pharmacokinetics that was dependent on both the dose and the anti-FITC antibody titer. The extended plasma duration of folate-FITC in immunized mice can be viewed as an advantage for maintaining a long-lasting accumulation of folate-FITC on FR-positive tumors. By extending the duration of treatment and optimizing the doses of therapeutic components (folate-FITC in combination with cytokines), enhanced antitumor activity with minimal toxicity was observed in mice bearing established subcutaneous tumors. Overall, our on-going research may allow for the identification of a more therapeutically effective, folate-hapten dosing regimen when given as immunotherapy in patients with FR-positive metastatic tumors.