tbuckley/cabot-search huggingface dataset:
Abstract 195: Cell death pathway activation during monocytic / macrophagic differentiation of hematopoietic tumor cell lines
Authors: João de Séllos, Mauricio S. Caetano, Erika Carvalho, Gustavo P. Amarante-Mendes, Carlos G. Ferreira, Cinthya Sternberg
Journal: Cancer Research (2011)

Abstract Apoptosis is a phenomenon of cellular degeneration highly conserved evolutionarily, being observed not only during development, but also associated with a number of diseases. Apoptosis is regulated by a complex set of proteins and accomplished by biochemical mechanisms that act to initiate and complete the destruction of the cell. Recently, typical biochemical and morphological changes associated to cell death were correlated with other vital cellular events, such as proliferation and differentiation. Despite the general tendency to treat apoptosis and cell differentiation as the result of different signaling pathways, several studies have shown that there is a high degree of morphological similarity between these events. The molecules involved in the regulation of apoptosis-like processes of differentiation have not been fully described. Since the main endogenous inhibitor of caspase-3 is the protein XIAP, which in turn is regulated by XAF1, we analyzed the expression of these proteins in the context of differentiation of different cell lines. The objective of this study was to evaluate the activation pathways of cell death in the process of monocytic/macrophage differentiation. We have observed that the expression of XAF1 protein decreases during monocytic/macrophage differentiation of HL60 cell line induced by PMA, but levels of its mRNA do not change. Interestingly, we have found that HL60 cell lines overexpressing either Bcl-XL or Bcl-2 cell lines have decreased expression of XAF1 due to methylation of its promoter. Also, besides rendering cells resistant to apoptosis as expected, HL60 cells overexpressing either Bcl-XL or Bcl-2 were more prone to differentiate by PMA treatment than parental cells. The correlation between high levels of mRNA expression of Bcl-2 with low expression of XAF1 mRNA was also observed in the analysis of samples from patients with follicular lymphoma retrieved from Oncomine database (www.oncomine.com). These results demonstrate the differential activation of pathways of cell death in monocytic / macrophagic differentiation, suggesting that a descrease in XAF1 expression is a necessary event during this process. Furthemore, our results reveal a transcriptional regulatory loop exerted by Bcl-2 family of proteins that had not yet been described. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 195. doi:10.1158/1538-7445.AM2011-195
GROUP PSYCHOTHERAPY AS ADJUNCT TREATMENT OF EPILEPTIC PATIENTS
Authors: ALBERT L. DEUTSCH, JOSEPH ZIMMERMAN
Journal: American Journal of Psychiatry (1948)

In our studies it was found that group psychotherapy is of definite value as an adjunct treatment of convulsive disorders in that 1. It attempted to eradicate the patient's fears concerning the disease. 2. It eliminated superstitions and misconceptions. 3. It gave the patient an opportunity to ventilate freely his fears and anxieties concerning the illness. 4. It was useful in discussing the availability of vocational rehabilitation, advisement and guidance, and training. 5. It served as a means of improving the patient-family relationship. 6. It produced "esprit de corps" and thus helped to eliminate the patients' feeling of being a social outcast. 7. It established a means of handling large groups of patients simultaneously on a therapeutic level.
P66 Inter-observer reliability of ultrasound to measure rectus femoris cross-sectional area in critically ill patients
Authors: B. Connolly, Z. Puthucheary, H. Montgomery, J. Moxham, N. Hart
Journal: Thorax (2011)

<h3>Introduction</h3> Ultrasound is a relatively simple, non-invasive, non-irradiating effort-independent tool to measure quadriceps rectus femoris cross-sectional area (RF<sub>CSA</sub>) in critically ill patients. We investigated the inter-observer reliability of the technique to validate its clinical utility in this group of patients. <h3>Methods</h3> Critically ill patients either in, or within 48 h discharge from, the Intensive Care Unit (ICU) underwent measurement of RF<sub>CSA</sub> using real-time B-mode ultrasonography using an 8MHz 5.6 cm linear transducer (PLM805, Toshiba Medical Systems Ltd, Crawley, UK) at a distance three-fifths from the anterior superior iliac spine to the superior patellar border. Where complete visualisation of RF<sub>CSA</sub> was not possible at this point, a more distal point of 2/3 of this distance was used. Ultrasound measurements were performed in turn by two critical care clinicians trained in ultrasound in a random order. The average of three consecutive measurements within 10% was taken as RF<sub>CSA</sub> for each patient. Both clinicians were blinded to the results of the other. <h3>Results</h3> 24 patients had RF<sub>CSA</sub> measurements performed using ultrasound (M:F 14:10; mean age 55.3±20.1 years). Inter-observer reliability was assessed by considering the level of agreement between RF<sub>CSA</sub> measurements for each patient between the two clinicians using intra-class correlation coefficients (ICC) adopting a two-way, random effects model for absolute agreement. An ICC of 0.99 (95% CI 0.97 to 0.99) was observed. Abstract P66 Figure 1 shows RF<sub>CSA</sub> images from both clinicians for one patient. <h3>Conclusion</h3> These data demonstrate high levels of inter-observer reliability between two trained critical care clinicians using ultrasound as a measurement technique for RF<sub>CSA</sub> in critically ill patients. RF<sub>CSA</sub> can be used as a novel, reproducible technique to track the trajectory of muscle loss in critically ill patients.
Abstract 5694: Targeted photothermal-chemotherapy with doxorubicin-loaded hollow gold nanospheres directed at EphB4 receptors
Authors: Jian You, Chiyi Xiong, Chun Li
Journal: Cancer Research (2012)

Abstract Photothermal ablation (PTA) is an emerging technique that uses near-infrared (NIR) laser light-generated heat to destroy tumor cells. Doxorubicin (DOX)-loaded hollow gold nanospheres (DOX@HAuNS) mediated simultaneous PTA of cancer cells and local drug release, resulting in enhanced antitumor activity. EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. The purpose of this study was to synthesize DOX@HAuNS conjugated to an EphB4 receptor-binding peptide, and evaluate the pharmacokinetics, biodistribution, and antitumor efficacy of the resulting EphB4-targeting DOX@HAuNS. A cyclic 17-mer peptide [c(TNYL-RAW) with high binding affinity to EphB4 was conjugated to DOX@HAuNS through a PEG linker. The cell uptake of c(TNYL-RAW)-conjugated Dox@HAuNS was examined in human ovarian cancer Hey cells over-expressing EphB4. The biodistribution tumor uptake of c(TNYL-RAW)-Dox@HAuNS was assessed at 24 h after intravenous injection in nude mice bearing Hey and A2789 ovarian cancers, and in nude mice bearing human MDA-MB231 breast tumors. Near-infrared (NIR) light-triggered Dox release in tumor-bearing mice was evaluated using a dual tracer-autoradiography technique. Antitumor effect was evaluated by measuring the tumor grow delay in mice bearing Hey ovarian cancer. In vitro, c(TNYL-RAW)-Dox@HAuNS were selectively taken up by Hey cells. This resulted in increased tumor uptake of targeted nanoparticles in all three EphB4-positive tumor models evaluated. Significantly higher cell killing effect against EphB4(+) A2780 cells was shown with DOX@c(TNYL-RAW)-HAuNS cells than with free DOX or DOX@PEG-HAuNS. In vivo, conjugation of c(TNYL-RAW) onto PEG-HAuNS did not cause significant change on pharmacokinetic properties of the nanoaprticles. DOX@c(TNYL-RAW)-HAuNS and DOX@PEG-HAuNS were almost completely eliminated from the blood at 48 h after injection. Treatment with targeted c(TNYL-RAW)-Dox@HAuNS followed by near-infrared laser irradiation (combined PTA and DOX therapies) resulted in significantly increased tumor growth control as compared to treatments with DOX@PEG-HAuNS-plus-laser (combined PTA and DOX therapies) and with PEG-HAuNS-plus-laser (PTA therapy alone). Mice in all treatment groups did not show lost in body weight, whereas free DOX caused ∼20% body weight loss at the equivalent DOX dose level. Targeted photothermal-chemotherapy exemplified by a single-agent nanoconstruct c(TNYL-RAW)-DOX@HAuNS is a promising approach to effective anticancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5694. doi:1538-7445.AM2012-5694
TCTAP A-134 Causes of Delay in Door-to-Balloon Time in South-East Asian Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction
Authors: An Shing Ang, Eran Wen Jun Sim, Mae Chyi Tan, Kevin Kien Hong Quah, Paul J.L. Ong, David Foo, Hee Hwa Ho
Journal: Journal of the American College of Cardiology (2015)
PTU-012 The impact of comorbidity on post liver transplant survival and resource utilisation in patients transplanted for acute liver failure utilising the Charlson comorbidity index
Authors: M A B Al-Freah, B Kok, W Bernal, G Auzinger, N D Heaton, J G O'Grady, M A Heneghan, J A Wendon
Journal: Gut (2012)

<h3>Introduction</h3> The presence of comorbidities negatively impact post liver transplant (LT) survival for those transplanted with chronic liver disease. <h3>Methods</h3> assess the impact of comorbidities on survival in patients transplanted for acute liver failure (ALF). <h3>Results</h3> 176 patients underwent LT for ALF over 9 years. Median follow-up was 92 months (range 35–142). Median age was 33 years (17–67) and 122 (69.3%) were females. Fifty-nine patients (33.5%) were transplanted for Paracetamol induced ALF. Ninety-six (54.6%) patients had ≥1 comorbidity. The commonest comorbidity was renal dysfunction in 84 (48%), pulmonary disease in 10 (6%), connective tissue disease in 5 (3%) and 2 (1%) had diabetes. Patients with ≥1 comorbidity had significantly increased 6 month (25% vs 13%, p=0.046), 12 month (27% vs 13%, p=0.023) and overall mortality (32% vs 17%, p=0.019). Similar results were demonstrated for graft survival. Recipient age ≥ 40 years (OR=1.37, 95% CI 1.02 to 1.86, p=0.039), the presence of comorbidity (OR=1.46, 95% CI 1.05 to 2.03, p=0.022) and renal dysfunction (OR=1.62, 95% CI 1.18 to 2.23, p=0.003) were associated with increased post LT mortality on univariate analysis. However, only the presence of comorbidity (OR=1.43, 95% CI 1.03 to 1.98, p=0.032) and renal dysfunction (OR=1.59, 95% CI 1.15 to 2.19, p=0.004) were independently associated with mortality. Other recipient related, donor, or graft variables were not associated with mortality. Patients with ≥1 comorbidity had significantly increased ICU length of stay (LoS) of 20 days (3 to 134) compared to those without comorbidities, 16 days (2–102), p=0.005. <h3>Conclusion</h3> Pre- LT comorbidity as defined by the presence of ≥1 comorbidity, significantly impairs overall post-LT patient and graft survival in patients transplanted for ALF. Patients with ≥1 comorbidity had significantly increased ICU LoS which may suggest increased resource utilisation. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Volk ML</b>, <i>et al</i>. Modified Charlson comorbidity Index for predicting survival after liver transplantation. <i>Liver Transplant</i> 2007;<b>13</b>:1515–20.
Abstract 886: Genetic polymorphisms in telomere pathway genes may potentially impact breast cancer survival
Authors: Jing Shen, Marilie D. Gammon, Mary Beth Terry, Qiao Wang, Patrick T. Bradshaw, Susan L. Teitelbaum, Alfred I. Neugut, Regina M. Santella
Journal: Cancer Research (2010)

Abstract Genetic polymorphisms are not only responsible for disease susceptibility, but may also play a role in determining cancer survival. We examined the associations between genetic variants of 9 genes involved in the telomere pathway in peripheral blood leucocytes (PBLs) and survival among breast cancer cases obtained from a population-based study – the Long Island Breast Cancer Study Project (LIBCSP). Fifty-two genetic variants were analyzed in the current study. Univariate and multivariate Cox regression analysis were used to test telomere length, genotyping and survival relationships. Telomere length had no significant relationship with overall and breast cancer specific mortality. Carrying genetic variants of the POT1 (rs7784168) A-allele and the TERT (rs2853677) TT genotype were significantly associated with increased all-cause mortality. The HRs were, respectively, 2.17 (95%CI: 1.01-4.66) and 1.73 (95%CI: 1.21-2.45) after adjusting for age at diagnosis (continuous), BMI (&amp;lt;25 vs. ≥25) and ER/PR status (both positive vs. either negative). The TERT (rs2853677) TT genotype alone was also significantly related with increased breast cancer specific mortality (HR=1.95, 95%CI: 1.24-3.06) after adjusting for age at diagnosis (continuous), BMI and ER/PR status. For ER/PR negative breast cancer cases, carrying the TERT (rs2735940) TT genotype was significantly associated with decreased breast cancer survival after adjusting for age at diagnosis (continuous), ethnicity (black vs. non-black) and BMI. The HR was 2.43 (95%CI: 1.30-4.55). Among ER and PR positive patients, carrying PINX1-33 (rs2277130) G-allele and the TERT-14 (rs2853677) TT genotype were also significantly associated with decreased breast cancer survival after adjusting for age at diagnosis (continuous). The HRs were 3.30 (95%CI: 1.35-8.06) and 2.56 (95%CI: 1.26-5.19), respectively. These data strongly suggest that genetic variants in telomere pathway genes (PINX1, POT1 and TERT) are potential valuable markers in predicting breast cancer survival. Acknowledgments Grant support: National Cancer Institute and National Institute of Environmental Health Sciences grants R03CA125768, U01CA/ES66572, P30ES009089 and P30ES10126; and awards from the Breast Cancer Research Foundation, and Women At Risk (WAR). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 886.
Evaluation of Corticosteroids in Hemophilia
Authors: Norman Trieger, Joseph J. McGovern
Journal: New England Journal of Medicine (1962)

A NUMBER of agents have been shown to increase capillary resistance without producing alterations in the coagulation mechanism.1 2 3 4 Corticosteroids, in particular, have been effectively used to control thrombocytopenic bleeding in the absence of an elevation of circulating platelet levels and to shorten prolonged bleeding5 6 7 8 and control hemorrhage in persons whose coagulation system is otherwise normal.The present communication reports the results of a controlled study of the use of corticosteroids (prednisone) as an adjunct to plasma replacement therapy in patients with hemophilia undergoing extraction of teeth.Methods and MaterialsFrom January 1, 1955, to January 1, 1960, 16 dental operations . . .
Abstract 3579: Prognostic and predictive role of JWA and XRCC1 expression in gastric cancer
Authors: Jianwei Zhou, Shouyu Wang
Journal: Cancer Research (2012)

Abstract Purpose: Polymorphisms in the DNA repair genes JWA and XRCC1 have recently been reported to increase susceptibility for gastric cancer, but the expression pattern and significance of these genes in gastric cancer is unknown. Experimental Design: Expression of JWA and XRCC1 were assessed by immunohistochemistry in three independent tissue microarray sets of gastric carcinoma (total n=1227), and paired adjacent non-tumoral tissues (n=80) with minimum five years follow-up time. Prognostic value of JWA and XRCC1 and of clinicopathologic factors, were evaluated in patients treated only with surgery. The predictive role of JWA and XRCC1 expression status in cases treated with adjuvant chemotherapy compared with surgery alone was analyzed. Results: JWA and XRCC1 protein levels were significantly downregulated in gastric cancer lesions compared with adjacent non-cancerous tissues (P &amp;lt; 0.001 for all correlations). Low tumoral JWA or XRCC1 expression significantly correlated with shorter overall survival (OS), as well as with clinicopathologic characteristics in patients without adjuvant treatment. Multivariate regression analysis showed that low JWA and XRCC1 expression, separately and together, were independent negative markers of OS. Adjuvant fluorouracil-leucovorin-oxaliplatin (FLO) significantly improved OS compared with surgery alone (log-rank test, P = 0.01), however, this effect was evident only in the JWA or XRCC1 low expression group (HR = 0.44; 95% CI = 0.26-0.73; P = 0.002, and HR = 0.44; 95% CI = 0.26-0.75; P = 0.002, respectively). Conclusions: JWA and XRCC1 protein expression in tumor are novel candidate prognostic markers and predictive factors for benefit from adjuvant FLO chemotherapy in resectable human gastric carcinoma. Acknowledgements: This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, the National Natural Science Foundation of China (30930080, 81001231), the Foundation of Cancer Center of Nanjing Medical University (08ZLKF08), and the Postdoctoral Science Foundation of China (20100481165). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3579. doi:1538-7445.AM2012-3579
A memorable patient: My namesake
Authors: R C Humphreys
Journal: BMJ (2001)

While reading in Mikhail Bulgakov's A Country Doctor's Notebook about the author's experiences of clinical situations that, as a newly qualified doctor in 1916, he was really quite unqualified to deal with, both in terms of education and experience, my mind turned to my own exposure to such problems when I was newly qualified in the 1940s. I think things are better now.

My baptism came one January night. I had done one surgical house job, and while awaiting my call up to military service, which came to us all in those days, I was filling in time as a locum for an elderly, singlehanded practitioner. Part of the practice remit was the care of a small midwifery unit.

The telephone rang in the small hours. “Night sister speaking, doctor. I have a primip who has been in the second stage for more than two hours. I think she needs a forceps delivery.”

Time spent on reconnaissance is never wasted, so I had a quick look at the book. “Assess the lie of the head. Which way are the ears pointing? Which blade goes in first? Why does this have to happen to me?”

I arrived at the unit. “Who gives the anaesthetic, sister?” I asked. I had not heard of pudendal block at that stage, and they would not have been equipped.

“You start her off, doctor, and I'll take over.”

Induction by chloroform with rag and bottle is perhaps as easy a ride as one can give a novice. To my surprise, it seemed to go reasonably well, and the low forceps delivery was easier than I had any right to expect.

Sister guided me through tying off the cord and delivering the placenta and then gave me a welcome cup of tea, which I drank while chatting to the new mother and making what I hoped were appropriate comments about her new son.

“What is your first name doctor?” asked the mother.

I was a little hesitant in answering. First names in those days, in contrast to today, were the preserve of family and close friends. “Richard,” I answered.

“Then I'll call him Richard.”

Driving back to my digs with that warm glow when the gods have been kind, I pondered. This business of names—it must be a frequent compliment.

After the army, and a couple of obstetric house jobs, I found myself in a country practice with its own cottage hospital and nine obstetric beds and a turnover of some 240 deliveries a year. Many years and scores of babies later, I retired, but it never happened again.

I wonder where young Richard is now? He must be 54.
Abstract P1-14-21: High antitumoral activity of neoadjuvant chemotherapy (NCT) with weekly paclitaxel + capecitabine and trastuzumab in patients with locally advanced HER2+ breast cancer (HER2+ LABC): Preliminary results.
Authors: P Augereau, P Raro, V Verriele, R Delva, S Abadie-Lacourtoisie, T Ceban, N Paillocher, I Valo, P Maillart, P Soulie
Journal: Cancer Research (2012)

Abstract Background: The addition of targeted agent (trastuzumab and/or pertuzumab and/or lapatinib) to NCT has dramatically improved pathological complete response rate (pCR) against HER2+ LABC. Early introduction of trastuzumab may be determinant as suggested by adjuvant trials while anthracycline free chemotherapy limits the risk of cardiotoxicity. Treatment and methods: From 01/2006 to 08/2011, 55 patients with HER2+ LABC (defined by 3+ or SISH+, confirmed by an expert pathologist) were considered for this regimen: paclitaxel 80mg/m2/wk D1/8/15 q4wk; capecitabine (fixed dose) 1500 mg bid, 5d/wk, 3 wk/4; trastuzumab (T) 4 mg/kg loading dose (D1 cycle1), 2mg/kg D1/8 and 4mg/kg D15 q4wk, for a total of 6 cycles (1 cycle = 4 weeks). Additional trastuzumab (6mg/kg) was given q3wk for 9 cycles. Mastectomy was considered for multifocal CIC, extended DCIS, initial inflammatory tumor and post operative radiotherapy was given if indicated. Patient characteristics: Median age: 58 years [28–84]; tumor stage II/III: 53%/47%; T1-2: 44%, T3: 36%, T4ac/d: 4%/16%; N0: 42%; median tumor clinical size: 4,6 cm [1–10]; grade III: 51%, HR−/HR+: 51%/49%. All patients were CT naïve. Results: Median follow-up was 27 months [9–74]. Clinical activity: major response (CR+PR) was observed in all patients (84% cCR). Pathological activity: 63,5% of patients achieved a tumor and nodal pCR (Sataloff TANA or NB, without residual invasive tumor cells), 22% had residual DCIS. According to hormonal receptor status (HR), pCR was 89% in HR−, 37% in HR+. Surgery was conservative in 37 patients (67%). 2 patients had locoregional recurrence (T4dN3, T3N1, both pCR and HR−). Toxicity (NCI-CTC scale):. Only 6 patients stopped either paclitaxel or capecitabine before the 6th cycle (1 at Cycle 3, 2 at cycle 5, and 3 at cycle 6). Main toxicities were: mucositis grade (gr) ½: 34%; diarrhea gr½: 27%; hand foot syndrome gr ½: 40%, gr 3: 9%; peripheral neuropathy gr ½: 39%, gr 3: 6%; asthenia gr ½: 47%, onychopathy gr½: 33%; gr 3: 6%; neutropenia gr 3: 9%, no febrile neutropenia. Two patients have a grade 2 reversible cardiotoxicity (LVEF &amp;lt; 50 %) Conclusion:. This NCT provided high pCR, specially in the HR- subgroup with a very favourable toxicity profile and merits further exploration. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-14-21.