tbuckley/cabot-search huggingface dataset:
Tobacco smoke-derived tumor promoter, hydroquinone, stimulates invasion of human hepatocellular carcinoma through induction of matrix metalloproteinase-9 expression
Authors: Syng-Ook Lee, Mi Hee Yu, Hyo Gwon Im, Yun-Jeong Jeong, Cheorl-Ho Kim, In-Seon Lee
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4995 

Cigarette smoking not only promotes tumorigenesis but also may increase metastasis of cancer cells. Although mounting evidence indicates that constituents of cigarette smoke are hepatic carcinogens and the liver is an organ susceptible to tobacco carcinogenicity, direct roles of the smoke constituents on invasion and metastasis of human hepatocellular carcinoma (HCC) are currently unknown. In this study, we examined the effect of hydroquinone, a tobacco smoke-derived tumor promoter, on the invasion of HCC with its detailed molecular mechanisms. Our findings indicated that hydroquinone potently induces MMP-9 expression and secretion in HepG2 human hepatoma cells, but not in other cancer cells, and this effect is correlated well with increased invasion of HepG2 cells in Matrigel invasion assay. Hydroquinone induced transcriptional activity of MMP-9 gene by activating AP-1, the well-known key element mediating MMP-9 gene expression, via MAPK signaling pathways. These results suggest that hydroquinone represents a potential metastatic factor present in tobacco smoke in HCC. Although data on smoking and risk for HCC are contradictory, the results from this study may support the reports showed a statistically significant positive relationship and a dose-response relationship between tobacco smoking and development of HCC.
The Impact of Concurrent Expression of MYC and BCL2 on Outcomes of Localized Primary Gastric Diffuse Large B-Cell Lymphoma Undergoing Rituximab-Containing Chemotherapy with or without Radiotherapy
Authors: Akihisa Kawajiri, Dai Maruyama, Akiko Miyagi Maeshima, Shin-ichi Makita, Hideaki Kitahara, Ken-ichi Miyamoto, Suguru Fukuhara, Tatsuya Suzuki, Wataru Munakata, Yukio Kobayashi, Kinuko Tajima, Jun Itami, Hirokazu Taniguchi, Kensei Tobinai
Journal: Blood (2014)
Abstract 2722: Poor Heart Failure Self-Care is a Worldwide Problem
Authors: Barbara Riegel, Andrea Driscoll, Jom Suwanno, Debra K Moser, Victoria V Dickson, Beverly Carlson, Jan Cameron
Journal: Circulation (2008)

Heart failure (HF) is reaching epidemic proportions across the world. Self-care, an integral component of therapy, is known to be poor in the US but little is known about self-care in other populations. In a descriptive, comparative study, 6 samples (2,082 adults) were drawn from 4 ethnically/culturally diverse locations in Australia, Thailand, and the US (blacks and whites in the northeast; Hispanics from the southwest). All investigators used the same general inclusion and exclusion criteria. All patients had a diagnosis of chronic HF objectively confirmed and all resided in a private residence where self-care was a reasonable expectation. Self-care was measured using carefully translated versions of the Self-Care of HF Index (SCHFI), which provided scores on self-care maintenance, management, and confidence. Data were integrated and analyzed using multivariate analysis after demographic (education), clinical (NYHA, newness of diagnosis), and treatment (participation in disease management) differences were controlled. When adequate self-care was defined as a standardized score ≥70%, self-care was inadequate in most categories in most groups (Figure ). After adjusting mean scores with covariates, group differences were still evident, with self-care maintenance lowest in the Thai and Hispanic samples (p&lt;.001), management and confidence lowest in the Thai sample (p&lt; .001), and confidence highest in the Hispanic sample (p&lt;.001). Self-care was poor in all of the samples. Intervention studies aimed at improving self-care are greatly needed in all the countries studied.
Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder
Authors: Christopher J. McDougle, Wayne K. Goodman, Lawrence H. Price, Pedro L. Delgado, John H. Krystal, Dennis S. Charney, George R. Heninger
Journal: American Journal of Psychiatry (1990)

Nine of 17 patients with obsessive-compulsive disorder responded when neuroleptic was added to fluvoxamine with or without lithium. Comorbid occurrence of tic spectrum disorders or of schizotypal personality disorder was associated with response. Abnormalities in brain dopamine and serotonin may be implicated in such patients.
Why does NICE not recommend laparoscopic herniorraphy?
Authors: D. Watkin
Journal: BMJ (2002)

Editor—Motson disagrees with the recommendation that laparoscopic herniorraphy has a limited role.1-1 But he managed to write the whole of his article without mentioning the fact that the Lichtenstein open mesh repair needs only a local anaesthetic.1-2 Instead, he makes the odd comment that “if the patient was unfit for general surgery then they would be limited to open operation under general anaesthetic.” Once you remove the need for a general anaesthetic open repair is far more cost effective.

Even more alarmingly, however, he does not include the use of local anaesthetic in his section on telling patients the options. Since local anaesthesia has many advantages this omission is surprising. His final statement, unsupported by any evidence other than a personal communication from another enthusiast for laparoscopy, implies that well informed patients will request laparoscopic repair. I could equally well state that well informed patients wish to avoid the expense and morbidity of general anaesthesia. Both statements reflect only vested interest and prejudice.
Training directors' opinions about the psychiatry resident in-training examination (PRITE)
Authors: L C Webb, S Sexson, J Scully, C F Reynolds, M F Shore
Journal: American Journal of Psychiatry (1992)

The American College of Psychiatrists conducted research to validate the content outline of the Psychiatry Resident In-Training Examination (PRITE) and to assess what residency training directors think about the examination.A mail survey was sent to the 218 psychiatry residency training directors who subscribe to the PRITE.The survey response rate was 70%. A majority of the respondents indicated agreement with the relative emphasis given to each content area in the PRITE (range = 52%-80% agreement). Eighty-one percent of the respondents were strongly in favor of continuing the practice of releasing the examination and the correct responses each year after the examinations have been scored. The majority of the respondents use results on the PRITE for individual resident evaluation and program evaluation (90% and 94%, respectively). Very few respondents use the PRITE results as the sole measure for assessing residents' cognitive competence or use it for marketing their residency programs.The survey provided strong support for the content areas covered in the PRITE and their relative emphases. The current practice of releasing PRITE items and answers (a main difference between the PRITE and the certification examination of the American Board of Psychiatry and Neurology) was well supported by the survey results. The stated purpose of the PRITE, to provide educationally useful feedback for individuals and groups in the form of comparisons with peers in specific areas of knowledge, was supported by a large majority of the respondents.
STUDIES ON RED BLOOD CELL DIAMETER
Authors: Greene Fitzhugh, Elbert Lapsley Persons
Journal: Journal of Clinical Investigation (1929)

Case 1: Liver started on 6th day.Case 2: Liver started on 4th day.Case 4: Liver started on 8th day.Case 5: Liver started on 2nd day.t The second decimal place is omitted in the table, but was used to determine the tio reticulocytes adult
Liver toxicity associated with sofosbuvir, an NS5A inhibitor and ribavirin use
Authors: Jessica K. Dyson, John Hutchinson, Laura Harrison, Olorunda Rotimi, Dina Tiniakos, Graham R. Foster, Mark A. Aldersley, Stuart McPherson
Journal: Journal of Hepatology (2015)

Hepatitis C virus (HCV) infection is a major cause of end-stage liver disease and hepatocellular carcinoma. There have been rapid advances in HCV treatment with the development of oral direct-acting antivirals (DAAs). Studies have shown sustained virological response rates above 90% with combinations of DAAs, including patients with compensated cirrhosis. Thus far, significant drug toxicity has not been seen with these agents, but there is limited experience of using DAAs in decompensated HCV cirrhosis. This report describes the first experience of serious drug-induced hepatotoxicity with the new DAAs. The mechanism underlying these drug reactions is currently unknown. Few patients with decompensated cirrhosis have been treated with DAAs, so the exact pharmacokinetics in this population have not been characterised. In both cases presented here, patients were taking or had recently taken other drugs. It is possible that an unknown interaction or reaction to the drug combination caused the hepatotoxicity. Although the association with the DAAs is not proven these cases indicate that patients with advanced liver disease need close monitoring while on DAA therapy and if there is a significant unexplained deterioration in liver function the DAAs should be discontinued.
Phase II evaluation of docetaxel (D) plus exisulind (E) in patients (pts) with androgen independent prostate carcinoma (AIPC)
Authors: V. J. Sinibaldi, K. Elza-Brown, J. Stewart, E. Rosenbaum, S. Denmeade, R. Pili, J. Walczak, S. D. Baker, M. Zahurak, M. A. Carducci
Journal: Journal of Clinical Oncology (2005)

4758 Background: Preclinical data suggested synergistic anti-tumor activity with the combination of D + E in AIPC. E is a GMP phosphodiesterase inhibitor administered orally. We designed a trial evaluating tumor response (↓PSA ≥50% lasting ≥4 wks) to D given on a weekly schedule + E daily. Methods: AIPC pts showing progressive disease after anti-androgen withdrawal were enrolled. Up to 2 prior chemotherapy (chemo) regimens were allowed. Planned treatment included 6 cycles of D 35 mg/m2 IV Q wk × 4 followed by 2 wks of rest. E 250 mg PO BID was initiated D 8. The statistical endpoint for this trial was the % of pts with ↓ in PSA ≥50% lasting ≥4 wks. A 2 stage trial was designed where the study would terminate if the % of pts meeting the endpoint was not convincingly >40%. If ≤3/14 pts responded in stage 1, this criterion would be met. During wks 1 and 3 serial plasma samples were obtained (last sample 168h). [D] were measured using a validated LC/MS/MS method and D pharmacokinetic (PK) parameters were determined by compartmental analysis. Results: From 3/29/02 - 11/11/03, fourteen pts were enrolled. Pt characteristics included median: age of 69.5 years (range 54–78), ECOG performance status of 1 (range 0–2), baseline prostate specific antigen of 76.65 ng/ml (range 28.3- 542.6), # prior hormonal manipulations of 2. Four pts had prior chemo and 1 had prior palliative RT. 85% had bone metastases; 50% had soft tissue (ST) measurable disease. Interim analysis revealed: 21% with a 50% decline in PSA level lasting ≥ 4 weeks; no ST disease responses. Significant toxicities (%) included: fatigue (14), nausea (28), diarrhea (7), abdominal pain (14), rash (7), syncope (21), pulmonary edema (7), CHF (14), superficial venous thrombosis (7) and elevations in transaminases (21), necessitating dose reductions and/or delays of D and E, in 71%, 64% of pts respectively. Paired D Pk data are available for 10 pts; mean ± SD clearance values were similar during wk 1 (45± 20 L/h) and wk 3 (40±25 L/h) (P≡0.07). Conclusions: This treatment does not compare favorably in efficacy or toxicity profile to other wkly single agent D regimens; nor does it compare favorably to the reported 58% PSA response with D given Q 3wks + daily E (Ryan et al., Semin in Oncol, 2001). Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis
Long-Term Outcomes in Patients With Diabetes Mellitus Related to Prolonging Clopidogrel More Than 12 Months After Coronary Stenting
Authors: Arun K. Thukkani, Kush Agrawal, Lillian Prince, Kyle J. Smoot, Alyssa B. Dufour, Kelly Cho, David R. Gagnon, Galina Sokolovskaya, Samantha Ly, Sara Temiyasathit, David P. Faxon, J. Michael Gaziano, Scott Kinlay
Journal: Journal of the American College of Cardiology (2015)
Long Term Results Of a Phase 2 Study Of Vincristine Sulfate Liposome Injection (Marqibo®) Substituted For Non-Liposomal Vincristine In CHOP With Or Without Rituximab For Patients With Untreated Aggressive Non-Hodgkin’s Lymphomas
Authors: Fredrick B. Hagemeister, Maria Alma Rodriguez, Steven R. Deitcher, Anas Younes, Luis Fayad, Andre Goy, Nam H. Dang, A Forman, Peter McLaughlin, Barbara Pro, Jorge Enrique Romaguera, Felipe Samaniego, Jeffrey A. Silverman, Andreas H. Sarris, Fernando Cabanillas
Journal: Blood (2013)
PI3K/Akt Signaling Interacts With Wnt/β-Catenin Signaling But Does Not Induce An Accumulation Of β-Catenin In The Nucleus Of Acute Lymphoblastic Leukemia Cell Lines
Authors: Tina-Susann Langhammer, Catrin Roolf, Saskia Krohn, Christin Kretzschmar, Rayk Huebner, Arndt Rolfs, Mathias Freund, Christian Junghanss
Journal: Blood (2013)
Abstract 11468: Role of Serotonin in Angiogenesis: Induction of Angiogenesis by Sarpogrelate via Endothelial 5-HT1B/Akt/eNOS Pathway in Diabetic Mice
Authors: Masaaki Iwabayashi, Yoshiaki Taniyama, Fumihiro Sanada, Junya Azuma, Kazuma Iekushi, Hiroshi Kusunoki, Amarnath Chatterjee, Keita Okayama, Hiromi Rakugi, Ryuichi Morishita
Journal: Circulation (2011)

Background:  Serotonin (5-hydroxytryptamine, 5-HT) plays a crucial role in pathophysiological conditions of peripheral artery disease (PAD) and diabetes mellitus (DM). In these conditions, the balance between the 5-HT2A receptor in smooth muscle cells and the 5-HT1B receptor in endothelial cells (EC) regulates vascular tonus. In the present study, we focused on the role of 5-HT in endothelial dysfunction using a selective 5-HT2A receptor blocker, sarpogrelate.   Methods and Results:  (in vitro) Stimulating Human Aortic Endothelial Cells (HAECs) with 5-HT (10μ M) upregulates eNOS expression and phosphorylation of eNOS, Akt and ERK1/2. In addition, a dose-dependent increase in tubule -formation was observed on Matrigel after 5-HT treatment (P   Conclusion:  Present study demonstrated that selective inhibition of 5-HT2A by sarpogrelate significantly restored ischemic limb blood perfusion in a severe diabetic mouse model through stimulation of the eNOS/Akt pathway via the endothelial 5-HT1B receptor. Enhancement of vasodilation and angiogenesis by sarpogrelate might provide a unique treatment for PAD and DM patients.
Abstract 1077: A Phase III Study of Microsomal Triglyceride Transfer Protein Inhibitor Lomitapide (AEGR-733) in Patients With Homozygous Familial Hypercholesterolemia: Interim Results at 6 Months
Authors: Marina Cuchel, Emma Meagher, A D Marais, Dirk J Blom, Hendrik d Theron, Amanda L Baer, LeAnne T Bloedon, William J Sasiela, Daniel J Rader
Journal: Circulation (2009)

Background: Patients with homozygous familial hypercholesterolemia (HoFH), caused by mutations in both LDL receptor alleles, are poorly responsive to existing cholesterol-lowering therapies and at ...
Kaposi's Sarcoma after Renal Transplantation
Authors: Matthew M Edey
Journal: New England Journal of Medicine (2005)

To the Editor: The regression of Kaposi's sarcoma in renal-graft recipients after switching from treatment with cyclosporine and mycophenolate mofetil to sirolimus, as reported by Stallone et al. (March 31 issue),1 is remarkable and confirms earlier observations.2,3 However, the immunohistochemical results in this study1 seem to be less convincing. The detection of Flk-1/KDR was reportedly performed on acetone-fixed kidney sections, but it is clearly stated that patients had no visceral involvement. Figure 2A, Figure 2B, and Figure 2C of the article do not seem to show greatly different vascular endothelial growth factor (VEGF) expression, certainly not in the range of . . .
2009 Ancel Keys Memorial Lecture—Drug Therapies for the Prevention of CVD Events: Trials and Errors
Authors: Bruce Psaty
Journal: Circulation (2009)

Drug therapies for risk factors such as high levels of blood pressure, lipids, and glucose represent, in Geoffrey Rose’s terms, a high-risk approach to a population-based problem. The purpose of these therapies is to prevent cardiovascular events, yet the US Food and Drug Administration generally approves new medications for these conditions on the basis of premarket studies that use surrogate end points. It is not feasible to address all questions about the efficacy and safety of drugs during the premarket phase, so postmarket evaluation is crucial. Historically, however, drug approval separates the period of intense evaluation from the period of intense marketing. Between 1980 and 2005, prescription drug expenditures increased from $12 to $200 billion. The expansion of the pharmaceutical industry in the second half of the twentieth century has provided a number of safe and effective medications for many conditions. The health of Americans has clearly benefited in quality and duration of survival. With several notable exceptions, however, the NIH has largely turned the evaluation of drug treatments over to industry, and the results of key NIH trials must often contend with industry marketing to influence practice. The duty to provide a return on investment to shareholders tends to create for industry an asymmetric interest in safety and efficacy. As a result, the design, conduct, and reporting of some industry-funded studies remain a public health problem. The current approach to the evaluation of the safety and efficacy of medications occasionally provides an unreliable patchwork of evidence about health outcomes and incomplete information about the risk–benefit profiles of new drug therapies. For medications that are well evaluated, single–risk-factor approaches to treatment decisions may limit their benefit to the population.
Doctors should advise but do not have to lead by example
Authors: P. O'Brien, J. Morrison, H. El-Refaey, S. Lawrence, S. J Bower, D. Peebles, M. Broadbent, A. Gordon, S. Burrell
Journal: BMJ (1995)

EDITOR,--We take issue with Simon Chapman's suggestion that medical students who smoke should be channelled away from primary health care.1 He argues that in view of our “responsibilities as exemplars” it is “hypocrisy” for doctors to smoke and that, consequently, if we do smoke it …
Abstract 3698: Acute Oral Loading of 1C Antiarrhythmic Drugs On-Top of Chronic Antiarrhythmic Therapy in Recent Onset Atrial Fibrillation
Authors: Giovanni L Botto, Mario Luzi, Giovanni Russo, Giorgio Cappelletti, Paolo L Pina, Franco Ruffa, Roberto Bonatti, Elena Butti, Rossana Lombardi, Giovanni Ferrari
Journal: Circulation (2006)
Corroboration of polymorphisms in the aromatase (CYP19A1) gene with response to neoadjuvant therapy with letrozole in postmenopausal women with stages II-II ER/PgR-positive breast cancer
Authors: J. A. Lopez-Guerrero, Z. Garcia-Casado, A. L. Guerrero-Zotano, A. Calatrava, A. Ruiz-Sauri, A. Fernandez-Serra, A. Ruiz, A. Llombart-Bosch, V. Guillem-Porta, A. Llombart-Cussac
Journal: Journal of Clinical Oncology (2007)

602 Background: Aromatase (CYP19A1) is the main enzyme implicated in estrogen biosynthesis. Polymorphisms in CYP19A1 can affect both aromatase expression and activity leading to changes in the estrogen levels. These changes have been previously associated with pathogenesis of estrogen-dependent diseases, including breast cancer. The purpose of this study is to evaluate whether the genotype of CYP19A1 can have an effect on the response to endocrine therapy with the aromatase inhibitor letrozole (L). Methods: We retrospectively analyzed a series of 58 postmenopausal women with stage II-III ER/PgR[+] breast cancer treated with L as neoadjuvant therapy. Response was evaluated by radiology (mammogram or ultrasound) at four months L (OMS) and data was available in 56 cases. A total of ten single nucleotide polymorphisms (SNPs) spanning the gene, a TCT insertion/deletion and a (TTTA) n repeat were evaluated. The (TTTA) n repeat was analyzed by using GeneScan to detect polymorphism length, TCT Ins/Del by direct sequencing and SNPs by allelic discrimination using TaqMan SNP Genotyping Assays (Applied Biosystems). Logistic regression analysis was used to estimate the most accurate predictive model for response to therapy. Results: Median age of our series was 77 years (range: 68 to 90). Twenty women (36%) responded to 4 months L, while 38 (67%) did not (2 PD and 36 EE). Allelic frequencies were determined for each polymorphism and the global genotype data was evaluated in a logistic regression analysis. In a first step, the analysis with the genetic information for the 12 polymorphisms resulted in a model that predicted radiological response to L with an accuracy of 80% (85% specifity, 69% sensibility). However, a reduction to 4 informative polymorphisms generated a simpler predictive model with an accuracy of 76% (76.5% specifity, 75% sensibility). Conclusions: Polymorphism analysis of CYP19A1 could predict for response to neoadjuvant therapy with L. A validation of this predictive model in an independent series is ongoing. No significant financial relationships to disclose.
Cardiac Iodine-123 Metaiodobenzylguanidine Imaging Predicts Sudden Cardiac Death Independently of Left Ventricular Ejection Fraction in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction
Authors: Shunsuke Tamaki, Takahisa Yamada, Yuji Okuyama, Takashi Morita, Shoji Sanada, Yasumasa Tsukamoto, Masaharu Masuda, Keiji Okuda, Yusuke Iwasaki, Taku Yasui, Masatsugu Hori, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2009)
Abstract 18008: The Burden and Morphology of Premature Ventricular Contractions in Patients Undergoing Cardiac Resynchronization Therapy
Authors: Mehmet K Aktas, Suneet Mittal, Scott McNitt, Slava Polonsky, Jonathan S Steinberg, Arthur J Moss, Wojciech Zareba
Journal: Circulation (2011)

Introduction: Frequent premature ventricular contractions (PVC's) limit effective delivery of cardiac resynchronization therapy (CRT). However, neither the burden nor morphology of PVC's is well defined in patients with ischemic (ICM) and non-ischemic (NICM) cardiomyopathy. Methods: In MADIT-CRT, 947 patients enrolled in the CRT-D arm underwent 24-hour 12-lead Holter monitoring. Patients with &gt;5000 PVC's were identified and the morphology of PVC's in each of these patients was assessed. Based on previously published ECG criteria, we characterized PVC's to originate from the RV or LV outflow tract, sinus of Valsalva, or a non-outflow tract location. Results: A total of 146 (15%) patients were identified, of whom 88 (60%) had ICM and 58 (40%) had NICM. The median total PVC count in ICM patients was 8807 as compared to 8950 in NICM patients, p=NS. PVC's with a LBBB morphology occurred in 34 (39%) ICM patients and 33 (57%) of NICM patients, p=0.03. In addition, RVOT appearing PVC's were significantly more frequent in NICM patients (19 (33%) vs. 11 (13%) in ICM patients, p=0.003). There was no difference in the number of PVC's that appeared to originate from the LVOT [ICM vs. NICM, 15 (17%) vs. 9 (16%), p=NS] or from the sinus of Valsalva [ICM vs. NICM 9 (10%) vs. 8 (14%), p=NS]. Non-outflow tract appearing PVC's were significantly more common in patients with ICM when compared to patients with NICM, 53 (60%) vs. 22 (38%), p=0.008. Conclusions: In 15% of patients undergoing CRT implantation, &gt;5000 PVCs were observed. While there was no difference in the burden of PVC between ICM and NICM patients, there were significant differences in morphology (and thus site of origin) of PVC's in the 2 groups of patients. These data may have implications, especially in patients in whom catheter ablation is necessary to eliminate PVC's in order to maximize CRT.