tbuckley/cabot-search huggingface dataset:
Abstract 270: Developing a Ventricular Fibrillation Cardiac Arrest Rat Model - Pitfalls and Challenges
Authors: Florian Ettl, Ingrid A Magnet, Wolfgang Weihs, Alexandra Warenits, Daniel Grassmann, Michael Wagner, Johann Sipötz, Ursula Teubenbacher, Fritz Sterz, Andreas Janata
Journal: Circulation (2013)

Introduction: The ideal rodent model of ventricular fibrillation (VF) cardiac arrest (CA) produces consistent histologic and neurologic damage as target for novel therapies and shows a high survival rate to minimize animal use and allow for long term outcome. VF induction, chest compressions and ventilation are crucial techniques and published in many variants in literature. We report our experiences during model development. Materials and Methods: A non-randomized cohort study evaluating different methods of VF induction, chest compressions techniques, mechanical ventilation and defibrillation was performed with regards to it’s feasibility, complications, ROSC rate and survival. Results: Male Sprague-Dawley rats (350g, anesthetised, instrumented) underwent VF induction with 2 min endocardial fibrillation via a transjugular neonatal pacing catheter with minimal current use, low incidence of autodefibrillation and good resuscitability. Mechanical chest compressions with approx. 30% of thorax diameter depth were applied with a pneumatic thumper 200/min placed mid-sternally, tilted upwards. Strong fixation with tapes avoided throrax-instability. Epinephrine (20μg/kg) and NaHCO3 (1mmol/ kg) were administered before CPR start and epinephrine repeatedly given after defibrillations every 2min. For defibrillations (5J, biphasic) modified paediatric defi pads were used. ROSC was achieved in 7/10 animals in a 6 min CA group and 6/11 in a 8 min CA group. CPR time was 2.6±1.0 min (mean±SD), number of defibrillations needed 2±1 and a cumulative epinephrine dose of 46±10 μg/kg with no differences between groups. Conclusions: Researchers developing a VF CA model are facing a multitude of difficulties, a lack of data on model development and many variations published in literature, often without detailed description. We developed a CPR rat model for VF CA with graded cognitive deficits and long-term survival. We propose detailed description of model development, including ineffective methods, to facilitate experience exchange between research groups, to avoid that future experimental groups repeat possible mistakes.
International comparison of the quality of voluntary adverse event reports for cremophor-containing paclitaxel-associated anaphylaxis submitted to regulatory agencies in the United States, Europe, and Japan
Authors: E. Calhoun, D. Raisch, H. Luu, E. Carias, L. Irizarry, M. Fisher, O. Sartor, C. Bennett
Journal: Journal of Clinical Oncology (2009)

6589 Background: Serious adverse drug events (sADEs) are a significant cause of morbidity and mortality. The FDA's MedWatch program is a voluntary adverse drug reporting program. In Europe and Japan, sADE reports are rarely reimbursed. We evaluated the quality of adverse events reporting in the US, Europe, and Japan for paclitaxel-associated anaphylaxis. Hypersensitivity reactions (presumably due to the diluent cremophor) occur in up to 42% of patients receiving paclitaxel (cremophor- containing paclitaxel was licensed in 1992, a cremophor-free paclitaxel was licensed in 2005). Methods: We reviewed reports of anaphylactic reactions to paclitaxel reported between 1997–2007 contained in the FDA Adverse Event Report System (AERS). Results: Of 171 unique case reports, 34% resulted in death. Cases that resulted in death were mostly incomplete in reporting descriptions of anaphylaxis symptoms and prophylaxis/therapy drug regimens in the US, Europe and Japan. (Table) The median duration between date of event and regulatory notification was 27, 55, and 18 days for the US, Europe, and Japan respectively. Conclusions: Overall, the quality of case reports of serious anaphylaxis reactions to cremophor-containing paclitaxel was poor in the US, Europe, and Japan, despite a substantial number of these reports being associated with death. Surprisingly, among the patients receiving prophylaxis with corticosteroids, anti-histamines, and/or H2-blockers, 36% of patients still died. [Table: see text] No significant financial relationships to disclose.
Dissociative symptoms in media eyewitnesses of an execution
Authors: A Freinkel, C Koopman, D Spiegel
Journal: American Journal of Psychiatry (1994)

The first execution in California since 1976 took place recently in the San Quentin Prison gas chamber. Eighteen journalists were invited as media eyewitnesses. The authors postulated that witnessing this execution was psychologically traumatic and that dissociative and anxiety symptoms would be experienced by the journalists.To investigate the prevalence and specific nature of these symptoms, questionnaires were sent to all the journalists about a month after the execution. The questionnaire contained 17 items assessing dissociative symptoms from the authors' questionnaire of 35 highly intercorrelated acute stress items. Fifteen of 18 of the witnesses returned the questionnaire. Items were endorsed on a scale of 0 ("have not experienced") to 5 ("very often experienced") and analyzed as being dichotomously present or absent. The mean age of the respondents was 37.6 (SD = 8.6) and mean years as a journalist were 15.2 (SD = 9.0). Nine subjects were men and six were women.Journalists witnessing the execution endorsed an average of 5.0 dissociative items, ranging from "I saw, heard, or felt things that were not really there" (endorsed by no one) to "I felt estranged or detached from other people" (endorsed by 60%). This prevalence of reported dissociative symptoms is comparable to that seen among persons who endured the recent Oakland/Berkeley, Calif., firestorm.The experience of being an eyewitness to an execution was associated with the development of dissociative symptoms in several journalists.
Can patients (pts.) with refractory germ cell tumors (GCT) be cured after progression following high dose chemotherapy (HDCT) with tandem transplant? Results with paclitaxel + gemcitabine
Authors: D. A. Lewis, M. J. Brames, L. H. Einhorn
Journal: Journal of Clinical Oncology (2006)

4588 Background: A previously published ECOG study of paclitaxel (P) plus gemcitabine (G) in refractory germ cell tumors achieved a 21% response rate (6 of 28 pts.) (JCO 20:1859, 2002). Two patients are continuously NED for 4+ years. Neither had prior HDCT. High dose salvage chemotherapy with carboplatin + etoposide and peripheral blood stem cell transplant has curative potential. Subsequent chemotherapy after progression following HDCT has only rarely achieved durable remission. We have retrospectively reviewed pts. treated at Indiana University with P + G after failure to cure with initial cisplatin combination chemotherapy and salvage HDCT (± other salvage regimens). Methods: 184 patients received salvage HDCT from February 1996 to December 2004. After further progression, 33 pts. were treated with P 100 mg/M 2 over 1 hour and G 1000 mg/M 2 over 30 minutes days 1, 8, and 15 every 4 weeks for a maximum of 6 courses. Pts. were ineligible if they received prior P or G. 26 pts. received P + G as 3 rd line, 6 as 4 th line and 1 as 5 th line chemotherapy. Results: Toxicity was primarily myelosuppression and neuropathy, as previously described with P + G (JCO 20:1859, 2002). There was no treatment related mortality. 10 of 33 pts. achieved objective response including 4 partial (2 to 6 months duration) and 6 complete responses (C.R.). 4 of the 6 C.R.s are continuously NED with P + G alone at 14 + , 34 + , 44 + , and 45 + months from start of P + G. One additional C.R. is currently NED 54 + months after P + G, with 2 subsequent resections of carcinoma. Conclusions: Long-term disease free survival and potential cure is possible with P + G in this patient population after progression following HDCT. [Table: see text]
Integrative Whole Transcriptome and Exome Sequencing Reveals Reprogramming Of Mantle Cell Lymphoma In Prolonged Early G1 Arrest For Clinical Response To Selective Inhibition Of CDK4 In Combination Therapy
Authors: David Chiron, Peter Martin, Maurizio Di Liberto, Xiangao Huang, Priyanka Vijay, Pedro Blecua, Scott A Ely, Olivier Elemento, Christopher E Mason, John P. Leonard, Selina Chen-Kiang
Journal: Blood (2013)
Abstract 71: A Dual PI3K-mTOR Inhibitor Induced Hyperglycemia and Increased Insulin Signals in the Heart
Authors: Xinhua Yan, Jillian Onufrak, Yongyao Yang, Juyong Lee, John Fuseler, Maoyun Sun, Sharath Sasi, David Goukassian, Lynn Hlatky, Robert L Price, Joseph Carrozza, Thomas K Borg, James P Morgan
Journal: Circulation Research (2014)

We previously reported that a dual PI3K-mTOR inhibitor BEZ235 (BEZ) induced cardiac hypertrophy. Here, we investigated potential mechanisms. Methods: three month old FVB/n female mice were treated with BEZ for five weeks. Cardiac function was monitored by serial echocardiography during the treatment and hemodynamic measurements at the end of the study. Cell signaling was analyzed by RT-PCR, Western blotting and ELISA. Results: BEZ induced a dose-dependent increase of left ventricular (LV) wall thickness and systolic function. These were associated with increased hypertrophic markers ANP, BNP, β-MHC and α-skeletal actin in the heart. In addition, in chronic BEZ-treated mouse hearts, the activations of PI3Ks, mTOR and ERK were increased. We conducted further studies to understand these contradictory results. We found that BEZ induced an increase of hepatic gluconeogenesis gene expression which was associated with increased fasting glucose, increased serum insulin level, a worsened glucose and pyruvate tolerance and increased IGFR/Insulin receptor activation in the heart. Injections of insulin lowered blood glucose, improved glucose and pyruvate tolerance, but further aggravated BEZ-induced cardiac dysfunction. On the other hand, OSI-906 (an IGFR/IR inhibitor) normalized cardiac function in BEZ-treated mice. Conclusions: Chronic BEZ treatment induced cardiac hypertrophy may be caused by increased insulin receptor activation in the heart.
TTF-1 in advanced SCLC – Diagnostic and prognostic relevance
Authors: Daniel Misch, Jens Kollmeier, Sergej Griff, Christian Boch, Kaja Zimmermann, Torsten Blum, Wolfram Grüning, Thomas Mairinger, Torsten Bauer
Journal: European Respiratory Journal (2011)

Background: The thyroid transcription factor-1 (TTF1) has an important role in differentiating primary lung from other adenocarcinoma. Furthermore, data indicate its possible prognostic implication on overall survival (OS) in adenocarcinoma patients. Beside the number of TTF1-negative SCLC, the diagnostic value in SCLC is limited as extrapulmonary small cell cancers (SCC) can show TTF1-expression due to their neuroendocrine differentiation. It is unknown if TTF1-expression is a prognostic factor in patients with SCLC.

Aim: To compare the OS of patients with SCLC stage III/IV according to their TTF1-expression.

Methods: We retrospectively analyzed 297 patients (f, n=111; m, n=186) with SCLC stage III/IV (UICC-6; stage IIIA, n=31; IIIB, n=87; IV, n=179) diagnosed between 01/05 and 12/08. TTF1-expression was prospectively evaluated and the OS of patients was compared between the group of TTF1-positive and TTF1-negative SCLC.

Results: TTF1 was available in 221 (74,4%) patients. Of these, 184 (83,3%) had TTF1-positive and 37 (16,7%) TTF1-negative SCLC. The percentage of TTF1-negative SCLC did not differ between the different stages (III, n=13 [15,3%]; IV, n=24 [17,6%]). Median survival was 533 (358-708) days for patients with stage IIIA, 447 (349-545) days for stage IIIB and 289 (238-340) days for stage IV patients. There was no significant difference in OS according to TTF1-expression in the entire patient population as well as in all three stages (entire population, TTF1-neg. 300 [241-359] days, TTF1-pos. 367 [294-440] days; p=0,30).

Conclusion: TTF1-expression has no diagnostic or prognostic relevance in SCLC patients. Therefore, the determination of TTF1-expression in SCLC is dispensable for clinical decision making.
The relationship between intraperitoneal volume and solute transport in pediatric patients. Pediatric Peritoneal Dialysis Study Consortium.
Authors: B A Warady, S Alexander, S Hossli, E Vonesh, D Geary, E Kohaut
Journal: Journal of the American Society of Nephrology (1995)

A multicenter study was conducted to determine the relationship between intraperitoneal volume and solute (e.g., urea, creatinine) transport as determined by the dialysate to plasma (D/P) ratio and mass transfer area coefficient (MTAC). Two 4-h peritoneal equilibration tests were conducted on each of 12 pediatric peritoneal dialysis patients (mean age, 10.8 yr; range, 0.2 to 19.2 yr). One test exchange volume was 900 mL/m2 body surface area (BSA), and the other was 1,100 mL/m2 BSA. Dialysate samples were collected at 0, 30, 60, 120, 180, and 240 min. Blood samples were drawn at 0 and 240 min. Solute equilibration was significantly more rapid with the 900 mL/m2 BSA exchange volume than with the 1,100 mL/m2 exchange volume when evaluated by the D/P ratio. In contrast, no differences in solute transport were noted with either exchange volume when assessed with the MTAC. In conclusion, solute D/P ratios vary with changes in the intraperitoneal volume, necessitating the use of a standardized exchange volume for the reliable interpretation of evaluations such as the peritoneal equilibration tests. In contrast, the use of the MTAC allows for an accurate assessment of solute transport over a wide range of exchange volumes.
Human error largely to blame for MSF hospital attack, US investigators say
Authors: Michael McCarthy
Journal: BMJ (2015)

Human error, technical failures, and violations of US army rules of engagement led to the night-time air attack on the Medecins Sans Frontieres (MSF) trauma center in Kunduz, Afghanistan last October.1 The attack left 30 patients, staff, and physicians dead and 37 wounded, the army investigation concluded.

Speaking from Kabul by teleconference, John F Campbell, commander of the US forces in Afghanistan, said that a report by the US military investigators found that personnel involved in the attack did not know that the compound they were targeting was the MSF trauma center but had failed to undertake the measures necessary to verify that the facility was a legitimate military target. “This was a tragic but avoidable accident caused primarily by human error,” Campbell said.

The report said that Afghan troops working with US special operations forces on the ground in Kunduz province had been under heavy attack by the Taliban for five days and nights when, on 2 October, they asked for close air support in a clearing operation that included clearing the National Directorate of Security headquarters building that Afghan special operations forces believed …
Immunohistochemical (IHC) determination of tumor cells in peritoneal washings pre- and post-resection (PW#1 and PW#2), peripheral blood (PB), cell saver waste (CSW) and cell saver blood (CSB) obtained during surgery for pancreatic cancer
Authors: N. Parchuri, B. Visvalingam, D. Kim, S. Pollack, H. Staszewski
Journal: Journal of Clinical Oncology (2004)

4240 Background: Prior studies have demonstrated the poor prognostic significance of positive peritoneal cytology in pancreatic cancer surgery. It has not been determined what significance positive peritoneal washings have by IHC. Nor has there been any studies on the significance of positive tumor cells determined by IHC in peripheral blood, cell saver waste or cell saver blood in patients with pancreatic cancer undergoing resection. Methods: We performed a retrospective review of specimens obtained from 17 patients with pancreatic cancer undergoing Whipple procedure between 10/99 - 3/02. PB, PW#1, PW#2, CSW, and CSB from the surgery were enriched with antiepithelial antibody coated magnetic immunoparticles and then stained with mouse monoclonal antibodies associated with pancreatic carcinoma. A Kaplan-Meier survival life table analysis was performed using the log rank test on all variables. Results: Conclusions: Patients with positive PW#2 had a median survival of 7 months and negative PW#2 had a median survival of 24 months (p<0.025). There were 5 patients with positive IHC for CSB but no difference in survival was seen compared to patients with negative CSB. There were 5 patients with positive PB by IHC but there was no survival difference compared to PB negative patients. IHC of post-resection PW may be a strong predictor of survival in patients undergoing Whipple resection of pancreatic carcinoma. No significant financial relationships to disclose.
Impact of renal insufficiency on cancer survival: Results of the IRMA-2 study
Authors: V. Launay-Vacher, N. Janus, J. Spano, J. Gligorov, I. Ray-Coquard, P. Beuzeboc, J. Morere, X. Pourrat, G. Deray, S. Oudard
Journal: Journal of Clinical Oncology (2009)

9585 Background: Data are scant on the potential impact of renal insufficiency (RI) on the morbidity and mortality of cancer patients. The IRMA-2 study was started to evaluate the potential association between RI and cancer survival. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005. Data included: sex, age, weight, serum creatinine, type of tumour, metastasis (bone and/or visceral). GFR was estimated with the abbreviated MDRD (aMDRD) formula at the inclusion. RI was defined as an aMDRD &lt;60 mL/min/1.73m 2 . Patients were retrospectively followed during 2 years after the inclusion. Survival analyses were performed with the log-rank test, survival median with the Mann-Whitney test, multivariate analysis with the Cox regression. Results: 4267 cancer patients (breast 1601, colorectal 575, lung 407, ovarian 269, prostate 224) with available data (aMDRD and follow-up) were included in the analysis. Median age 59.0, mean weight 66.2, 62.9% were women. 51.2% of these patients were alive at the end of the follow-up. RI was strongly linked to mortality (p&lt;0.0001), when analysing all type of patients and tumors. When the same analysis was performed for non-metastatic patients (n=2382), RI was also associated with mortality (p&lt;0.0001). Similar results were found when comparing the survival medians of the same populations ( table ). Finally, 2 Cox models adjusted for sex, age, and the 5 main types of tumor were associated with a significant increase in the risk of death for patients with aMDRD&lt;60 as compared to patients without ( Table ). Conclusions: IRMA-2 is the first large scale study reporting an association between RI and a reduced cancer survival. Cancer patients with aMDRD&lt;60 seemed to be more at risk of death for the following 2 years even in non metastatic patients. IRMA-2 underlines that assessing, monitoring and managing renal function in cancer patients is crucial in order to prevent or at least minimise renal dysfunction because of its potential impact on survival. [Table: see text] No significant financial relationships to disclose.
Ifosfamide given once every other week: A clinical and pharmacological study
Authors: W. Cacheux, B. Gourmel, J. Alexandre, N. Germann, F. Rabillon, F. Goldwasser
Journal: Journal of Clinical Oncology (2007)

13008 Background. Ifosfamide (IFM) is a bi-functional alkylator with wide spectrum of activity in solid tumors and has an auto-inductive liver metabolism through P450 cytochromes. Auto-induction might permit a better therapeutic index for combination therapy. Methods. A phase I trial with interpatient dose escalation of a single dose of IFM given every 2 wks in advanced solid tumor pts. IFM, its dechloroethylated and active 4-hydroxy metabolites, were measured at cycle 1 &amp; 2 at the end of infusion, 2 and 5h later, using gas chromatography. IFM elimination was considered as following a monocompartimental model kinetics. Results From January 2004 to June 2006; 20 pts of PS&lt;2 were included :10 F, 10 M, median age 61 years (39–78), median previous chemotherapies: 2 (0–5). Primary tumor was most often ovarian (5), peritoneal (3), sarcoma (2), melanoma (2), or miscellaneous (8). 10 pts received 2.5g/m 2 and other 10 pts received 3g/m 2 . A total of 79 cycles were evaluable for toxicity. median number of cycles: 4 (1–8). No Grade (Gr) 3–4 hematologic toxicity, no alopecia. Gr2 nausea and fatigue were the most common toxicities at 3g/m 2 . No toxicity-related fatal event was noted. One objective response was noted in pancreatic cancer pt and one sustained CA125 decline in a heavily pretreated ovarian cancer pt. A slight (7–10%) but reproducible decrease of AUC was detectable at cycle 2, at both dose levels, related to auto-inductive metabolism (see table below). The other PK results are available and will be presented (Table). Intra individual variations (large SD) were noticed for each pharmacokinetic (PK) parameter. Conclusions: A slight non dose- dependent but rather patient-dependent auto-induction of IFM metabolism was detected. The toxicity profile allows the development of every 2 wks IFM-based combination therapies. [Table: see text] No significant financial relationships to disclose.
Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats
Authors: Yuanyuan Ji, Aijun Zhang, Xiaobin Chen, Xiaoxia Che, Kai Zhou, Zhidong Wang
Journal: Acta Pharmaceutica Sinica B (2016)

Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague-Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing.