tbuckley/cabot-search huggingface dataset:
Abstract 13651: Thrombomodulin Variants are Associated with Increased Mortality following CABG Surgery in Replicated Analyses
Authors: Robert L Lobato, William D White, Joseph P Mathew, Mark F Newman, John H Alexander, Mihai V Podgoreanu
Journal: Circulation (2010)

We tested the hypothesis that genetic variation in thrombotic and inflammatory pathways is independently associated with long-term mortality following coronary artery bypass grafting (CABG). Method...
Syphilis epidemiology in Sweden: re-emergence since 2000 primarily due to spread among men who have sex with men
Authors: I Velicko, M Arneborn, A Blaxhult
Journal: Eurosurveillance (2008)

Syphilis has re-emerged in western Europe since 2000. Changes in sexual behaviour have facilitated the spread of syphilis especially among men who have sex with men (MSM) and improved surveillance systems and case detection have lead to an increase in the reported numbers of cases. This report describes recent trends (2000-2007) of syphilis in Sweden, where the spread among MSM, particularly in the big cities, has been a major contributor to an increase in cases. Estimated syphilis incidence among MSM was up to twenty-eight times higher than in the general Swedish male population. The most affected age group among males was 25-44 years of age. The majority of infections in men and women through heterosexual contacts were acquired abroad whereas the majority of infections attributed to sex between men were acquired in Sweden. Appropriate prevention activities are needed to reach vulnerable populations in Sweden.
Psychological debriefing
Authors: P. Boyce
Journal: BMJ (2001)

Editor—Small et al have shown the ineffectiveness of debriefing in reducing maternal depression after operative childbirth.1 Although we agree with the general findings of their study2 some methodological issues must be addressed, especially if their findings are interpreted to mean that women should not have the opportunity to talk about their delivery experiences in a therapeutic and supportive manner.

The authors assert that the expected prevalence of postnatal depression is 24%3; this is considerably higher than the 13% reported in other studies.4 They assessed postnatal depression using the Edinburgh postnatal depression scale at six months postpartum (when its validity is uncertain), thereby excluding women who had had postnatal depression earlier but then recovered.

Additionally, there is no indication in this study of the degree of stress associated with the delivery, and elective and emergency procedures were aggregated. In our clinical experience a forceps delivery is more traumatic than an elective caesarean section.

Although a good response rate was achieved on the 1041 postal questionnaires, 662 eligible women did not participate (275 women declined to participate and participation was declined by the woman's doctor for 387 women), and 710 eligible women were discharged too soon to complete the study; therefore, less than half of all eligible participants actually entered the study. This calls into question the representativeness of the sample.

Little detail is provided about the debriefing. Lee et al have highlighted the desirability of a debriefing after miscarriage being conducted by someone who could provide factual information and answer questions about the event.5 The research midwives would not have been present at the delivery and may not have been able to address specific issues raised by the participants. Furthermore, in their views of postpartum care the women who had been debriefed did not differ from the women who had had standard care (information from table on the BMJ's website available at www.bmj.com/cgi/content/full/321/7268/1043/DC1). This could mean that all women received fundamentally good clinical care or that the debriefing was not sufficiently useful.

Debriefing is aimed at preventing post-traumatic stress disorder, not depression. It is questionable whether a single session of debriefing would have an impact on the onset of postnatal depression when other psychosocial variables contribute more to its onset.

While we agree with the general thrust of this paper, which shows the ineffectiveness of debriefing, it is important to remember that after undergoing a traumatic delivery women should be provided with good clinical care which includes the opportunity to talk about their experiences of delivery.
Ongoing rubella outbreak in Bosnia and Herzegovina, March-July 2009 - preliminary report
Authors: A Novo, J M Huebschen, C P Muller, M Tesanovic, J Bojanic
Journal: Eurosurveillance (2009)

Between 24 March and 31 July 2009, 342 clinically diagnosed cases of rubella were notified in five municipalities in Republika Srpska, Bosnia and Herzegovina. Fourteen cases were laboratory-confirmed by positive IgG against rubella virus. Four virus isolates were obtained and identified as genotype 2B strains, with one isolate differing by a single mutation in the region of the E1 gene. This ongoing outbreak revealed gaps in the immunisation programme during the war in BiH (1992-1995) and highlights the need to revise legislation to permit immunisation of children above 14 years of age with measles, mumps, rubella (MMR) vaccine and to introduce supplemental immunisation activities.
Fluphenazine plasma levels, dosage, efficacy, and side effects
Authors: D F Levinson, G M Simpson, E S Lo, T B Cooper, H Singh, K Yadalam, M J Stephanos
Journal: American Journal of Psychiatry (1995)

The authors sought to determine whether fluphenazine dose or plasma level predicts clinical improvement or side effects during acute treatment.Oral fluphenazine was given in fixed, randomized, double-blind doses (10, 20, or 30 mg/day) for 4 weeks to 72 inpatients with acute schizophrenic exacerbations. Outcome measures included percentage improvement in ratings of positive symptoms (hallucinations, delusions, and thought disorder), percentage improvement in negative symptoms, and maximum score for extrapyramidal symptoms. Response was defined as an improvement in positive symptoms of 40% or more.The 42 responders had a shorter duration of illness, less chronic course, and lower rate of akathisia. Plasma level and dose did not differentiate responders and nonresponders, but they did predict percentage improvement in positive symptoms within the responder subgroup. Akathisia was more common and extrapyramidal symptoms were more severe at higher plasma levels.Responders showed the greatest improvement at fluphenazine plasma levels above 1.0 ng/ml and doses above 0.20-0.25 mg/kg per day. Since the literature suggests that optimal plasma levels are similar during acute and maintenance treatment, monitoring of plasma levels may thus be useful. Conditions for applying the "responder-only" analytic strategy in future studies are discussed.
Current medication use and symptoms of depression in a general population
Authors: Craig Tj, Van Natta Pa
Journal: American Journal of Psychiatry (1978)

In a community survey, 41.8% of 771 men and 60.2% of 1,059 women reported having used one or more medications in the 48 hours before the interview. The use of medications and the number of medications used increased progressively with age among both men and women. Respondents who used four or more medications included significantly more high scores on a depression checklist than those who used fewer medications. The group of women who used minor tranquilizers and sedatives included significantly more high depression scorers than those who did not. Among both sexes, those scoring in the depressed range who were receiving psychotropic medication tended to be taking minor tranquilizers or sedatives.
Perioperative chemotherapy with epirubicin, cisplatin, and 5-FU (ECF) for gastroesophageal cancer: A retrospective analysis.
Authors: D. Bichev, K. Breithaupt, Y. Dogan, C. Grieser, T. E. Pfiffer, S. Daum, C. Treese, G. Schumacher, B. Dörken, P. C. Thuss-Patience
Journal: Journal of Clinical Oncology (2010)

e14623 Background: Perioperative chemotherapy with ECF is the recommended treatment in Europe. We report our experience with this treatment. Methods: In this retrospective analysis all the pts from 09.2004 to 09.2008 with adenocarcinoma of the distal esophagus, gastroesophageal junction (GEJ) and gastric body who received preoperative ECF (Cunningham et al., 2006) with curative intent were included. Cisplatin and 5-FU were substituted with oxaliplatin or capecitabine, if indicated. Preop staging included MSCT-scan of chest and abdomen, endoscopy and endosonograpy. Pts were planned to receive 3 preop and 3 postop cycles of ECF. Results: 55 pts were analysed. Median age 64 (range 32- 79), male 43 pts. Tumor site: distal esophagus 5, GEJ: 26, gastric 24 pts. Surgery: none: 4 pts, curative: 43 pts, palliative: 8 pts; esophageal resection: 16 pts, total gastrectomy: 29 pts, subtotal gastrectomy: 3pts, other: 3 pts. D2 lymph node dissection: 43 pts. Preop chemotherapy: ECF 50 pts, EOF 4 pts, ECX 1 pt. All 3 planned preop cycles administered in 80% of pts. Postop adjuvant chemotherapy initiated in 42% of pts. 31% of pts received 3 postop cycles. Postop palliative chemotherapy: 14.5% of pts. Main non hematological toxicity of curative chemotherapy CTC grade 3 and 4 (preop/postop): 48/21 pts evaluable: Nausea 0/4.8%, diarrhoea 2.1/4.8%, infection 0/4.8%, mucositis 0/0%. Hematologic toxicity CTC grade 3 and 4 (preop/postop): 45/18 pts evaluable: Neutropenia 49/83%, thrombopenia 0/11%. Surgical complications of 51 pts operated: pulmonary complications 10 pts, bleeding 2, wound healing 2, anastomotic leakage 3, cardiac complications 7, pulmonary embolism 1, septicaemia 2, 30 day mortality: 3.6%. Pathologic resection of 51 operated pts: R0 78.5%, R1 17.5%, R2 4%. Median follow-up 17.1 mths. So far 23 pts had tumor recurrence and 22 pts died, 16 of them tumor related. The cumulative survival at 1 year is 74.8%. Conclusions: Our experience is concordant with the published data. Preop ECF based chemotherapy is better tolerated than postop ECF and can be administered to a higher proportion of patients. Overall ECF is a safe and well tolerated regimen, and does not seem to increase surgical complication rates. No significant financial relationships to disclose.
Overdose and prescribed opioids: Associations among chronic non-cancer pain patients
Authors: Kate M Dunn, Kathleen W Saunders, Carolyn M Rutter, Caleb J Banta-Green, Joseph O Merrill, Mark D Sullivan, Constance M Weisner, Michael J Silverberg, Cynthia I Campbell, Bruce M Psaty, Michael Von Korff
Journal: Annals of Internal Medicine (2010)

In response to growing awareness of chronic pain as a significant patient concern, chronic opioid therapy is prescribed with increased frequency,(1-3) with over 3% of adults now receiving chronic opioid therapy for chronic non-cancer pain (CNCP).(​2) Concurrently, death rates from opioid analgesic poisoning have increased.(4-8). From 1995-2004, opioid-related poisoning hospitalizations doubled in Washington State.(9) A recent study in West Virginia reported that less than half (44%) of autopsy-identified unintentional prescription drug overdose fatalities had received opioids from a physician, suggesting that overdose typically resulted from drug diversion.(10;11) However, overdose risks in patients receiving medically prescribed opioids have not been studied.

Some hold that the rise in poisonings is related to excessive use of opioid analgesics in community practice.(12) Others express concern that such interpretations may lead to under-prescribing of opioids for CNCP patients.(13) The association of prescription opioid exposure and overdose risk has been inferred from: uncontrolled case series of autopsies subject to selection biases or ecological time series studies where individual-level associations cannot be examined. While opioids provide partial pain relief for chronic pain.(14-15), the balance of long-term risks and benefits is poorly understood.(16-21) Large-scale epidemiologic studies assessing patient use of prescribed opioids are needed to assess whether there is a relationship between receiving medically prescribed opioids and opioid-related poisonings. A key unanswered question is whether overdose risk differs by opioid dose among patients receiving chronic opioid therapy.

The objectives of this report are: 1) to estimate overall overdose rates (non-fatal and fatal) among persons receiving opioids long-term for CNCP from medical sources; and, 2) to compare risks of opioid overdose among patients recently receiving chronic opioid therapy at differing dosage levels.
Abstract 1810: Vitamin K Epoxide Reductase Complex Subunit 1 (vkorc1) Gene Polymorphism is Associated with Atherothrombotic Complication after Drug-Eluting Stent Implantation : Two Center Prospective Cohort Study
Authors: Jung-Won Suh, Jin-Shik Park, Hyun-Jae Kang, In-Ho Chae, Dong-Ju Choi, Hun-Jun Park, Pum-Joon Kim, Sang-Hong Baek, Ki-Bae Seung, Hyo-Soo Kim
Journal: Circulation (2008)

Single nucleotide polymorphisms (SNPs) of Vitamin K epoxide reductase complex subunit 1 (VKORC1) affect warfarin dose response. Recently, SNP of VKORC1 +2255 was reported to have association with arterial vascular disease. However, it is not known whether SNP of VKORC1 affects clinical outcomes among patients who underwent drug-eluting stent (DES) implantation. We prospectively collected genomic DNA in patients who underwent DES deployment from Sep 2003 to Dec 2006 and compared clinical outcomes according to their VKORC1 genotype. The primary end-point was composite of atherothrombotic events [cardiac death, myocardial infarction, and non-hemorrhagic stroke]. Mean follow-up duration was 631±251 days. Genotyping was completed in 764 cases (TT genotype (n=640, 83.8%) vs. non-TT (CC or CT) genotype (n=124, 16.2%)). Non-TT group showed more composite events events than TT group (7.3% vs, 3.0%, p=0.032). In the Cox regression analysis, non-TT genotype of VKORC gene was a significant predictor of atherothrombotic events (Hazard ratio 2.56, 95% confidence interval 1.14±5.78). In the event-free survival analysis, non-TT group also showed significantly poorer cardiovascular events-free survival rate than TT group (p=0.02). VKORC1 genotype is associated with cardiovascular events in patients with DES implantation, suggesting the role of coagulation system.
Malignant pleural mesothelioma-targeted CRI1 promoter system for gene therapy and virotherapy
Authors: Takuya Fukazawa, Junji Matsuoka, Yoshio Naomoto, Toru Nakai, Yutaka Maeda, Mary Durbin, Noriaki Tanaka
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1348 

Malignant pleural mesothelioma is an aggressive tumor of mesenchymal origin and is increasing worldwide as a result of widespread exposure to asbestos that was widely used in industrialized countries until approximately 1970. The median survival of patients with mesothelioma from time of diagnosis ranges between 1 and 2 years. Despite considerable advances in the understanding of its pathogenesis and etiology, malignant mesothelioma remains largely unresponsive to standard modalities of cancer therapy.    In order to design a system for specific gene therapy and virotherapy to treat malignant mesothelioma, we evaluated the specificity of the promoters of four different mesothelioma-specific genes: Calretinin, WT1 (Wilms' tumor suppressor gene), Mesothelin and CRI1 (CREBBP/EP300 inhibitory protein 1). Transient transfection assay demonstrated that the CRI1 promoter is highly active in malignant pleural mesothelioma cells (H2452, MSTO-211H, H2052, H28) but much less active in normal mesothelial cells and pleural cells. However, the other three promoters of mesothelioma-specific genes (Calretinin, WT1 and Mesothelin) showed high promoter activity not only in the mesothelioma cells but also in normal cells.    Four tandem repeats of the CRI1 promoter (CRI1-138 4x) caused significantly high promoter activity in malignant pleural mesothelioma cells but little promoter activity in normal mesothelial cells and normal fibroblasts. The recombinant adenoviral vector expressing pro-apoptotic BID (BH3 interacting death agonist) driven by the CRI1-138 4x promoter induced apoptosis in malignant mesothelioma cells but not in normal cells. Moreover, the conditionally replicating adenovirus (CRAd) expressing E1A driven by the CRI1-138 4x promoter induced cell death in mesothelioma cells and demonstrated anti-tumor effects in a mesothelioma xeno-graft mouse model. Here, we describe a novel strategy to target malignant mesothelioma using the CRI1-138 4x promoter system.
Abstract 12783: Analysis of SCN5A mutation and Antiarrhythmic Drug in Chinese Patients with Short QT Syndrome
Authors: Kui Hong, Hui Zhou, Su Juan Yan, Jinzhu Hu, Xiao Gang Peng, Xiao Shu Cheng, Pedro Brugada, Ramon Brugada
Journal: Circulation (2012)

Aims. We present, for the first time, that loss-of-function mutations in the SCN5A gene encoding for the strong depolarization channel Nav1.5 contribute to SQTS. Methods and Results. We recruited n...
Abstract B107: BET proteins are key mediators of pancreatic cancer cell growth and its tumor microenvironment
Authors: Andrew S. Liss, Sabikun Nahar, Jennifer A. Mertz, Barbara Bryant, Robert J. Sims, Carlos Fernandez-del Castillo, Keith D. Lillemoe, Andrew L. Warshaw, Sarah P. Thayer
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is extraordinarily chemoresistant and the abundant stromal content of these tumors contributes to the ineffective treatment of this disease. While the genetic alterations of PDAC have been well characterized, the epigenetic pathways regulating PDAC remain, for the most part, elusive. Employing an in vivo shRNA screen targeting 150 epigenetic regulators we identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC cell growth and maintenance of the tumor stroma. PDAC cells are broadly dependent on the activity of BET proteins, as the growth of 17/20 cell lines was sensitive to the BET inhibitor CPI203. BET family members contribute to PDAC cell growth by modulating the expression of MYC and the activity of GLI, two key transcriptional programs. Xenograft tumors in mice treated with BET inhibitor exhibited little to no growth, while tumors in control mice grew to 5 times their starting size. In addition to diminishing the proliferation of cells in these tumors, BET inhibition also effects the tumor stroma. A four-fold reduction in fibroblast content of tumors was observed which correlated with a 60-90% down-regulation of a key mediator of the tumor microenvironment, SHH, within the cancer cells. Taken together, these results suggest that therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. Citation Format: Andrew S. Liss, Sabikun Nahar, Jennifer A. Mertz, Barbara Bryant, Robert J. Sims, III, Carlos Fernandez-del Castillo, Keith D. Lillemoe, Andrew L. Warshaw, Sarah P. Thayer. BET proteins are key mediators of pancreatic cancer cell growth and its tumor microenvironment. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B107.
Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Analysis Of The CLL10 Trial, An International, Randomized Study Of The German CLL Study Group (GCLLSG)
Authors: Barbara Eichhorst, Anna-Maria Fink, Raymonde Busch, Elisabeth Lange, Hubert Köppler, Michael Kiehl, Martin Sökler, Rudolf Schlag, Ursula Vehling-Kaiser, Georg Köchling, Christoph Plöger, Michael Gregor, Torben Plesner, Marek Trneny, Kirsten Fischer, Hartmut Döhner, Michael Kneba, Clemens Wendtner, Wolfram Klapper, Karl-Anton Kreuzer, Stephan Stilgenbauer, Sebastian Böttcher, Michael Hallek
Journal: Blood (2013)
Trastuzumab and adoptive transfer of autologous tumor-stimulated T lymphocyte in refractory recurrent breast cancer: A pilot study
Authors: Uhi Toh, Teruhiko Fujii, Naoko Seki, Goro Yokoyama, Sino Nakagawa, Etsuyo Ogo, Kazuo Shirouzu, Hideaki Yamana
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

640 

Purpose: Recent accumulating data indicate that therapeutic efficacy of anti-tumor antibodies might be in part attributed to the ADCC activity and induction of tumor specific T cell immunity mediated by FcR on dendritic cells. Immune dysfunction might be a limited factor in antiboby therapy with advanced cancer patients. Based on these knowledge, a clinical trial was performed to test therapeutic efficacy of Trastuzumab combined with immunotherapy in patients with HER2+ breast cancer. Method: 14 pts with recurrent breast cancer (7 HER2+; 7 HER2-), who had failed the conventional chemoradiotherapy., were enrolled in this study. The tumor cell suspensions were prepared by mincing and enzymatic digestion of the biopsied fresh tumors. AuTL was generated in vitro by co-culture of peripheral blood lymphocytes (PBL) and irradiated autologous tumor cells in RPMI 1640 medium supplemented with rIL-2 (100 u/ml) for 7-14 days. The surface markers of the generated AuTLs and cytokine productions were analyzed by Flow Cytometry and ELISA, respectively. The killing activity and IFN-g production against autologous tumor cells were also evaluated in presence or absence of Trastuzumab (100 ug/ml). These AuTLs were administrated in the patients by intra-peritumoral injection biweekly, and Trastuzumab (2mg/kg) was systemically infused for the HER2+ patients weekly. The treatments were repeated for 6 to 11 cycles, in which total numbers of administered T cells ranged between 3.2 x 109 and 4.6 x 109. Results: The generated AuTLs were preponderantly CD3+CD4+ / CD3+ CD8+ T cells and CD3-CD56+ NK cells and showed significant degrees of cytotoxic activity and IFN-g production against autologous tumor cells and also HLA matched allogenic tumor cell lines in 4 out of 6 cases tested. ADCC was enhanced in 4 cases. The clinical response showed the one PR and seven NCs in these 14 pts. It is noted that carcinomatous pleural effusion was disappeared or well controlled in 6 pts and tumor marker proteins (CEA, CA15-3, TPA)were markedly decreased in 5 pts. The adverse effects of the immunotherapy were tolerable with grade 1∼2 infusion reaction of fever, nausea and fatigue, and no cardiac dysfunction was observed. CONCLUSIONS: Clinical responses with the intra-peritumoral AuTL injection were observed in patients with refractory recurrent breast cancer. These preliminary data suggest that the strategy of the combination therapy may benefit heavily refractory recurrence breast cancer patients.