tbuckley/cabot-search huggingface dataset:
SP0145 Challenges faced by parents with a child having a rheumatic disease
Authors: M. Bukovský, S. Bukovská
Journal: Annals of the Rheumatic Diseases (2013)

There are multiple challenges parents of a chronically ill child have to face. The background family situation including psychological and socioeconomic factors plays a major role in the development of coping strategies. Onset of Juvenile Idiopathic Arthritis (JIA) in a previously healthy child appears the most difficult time. Acceptance and understanding of the disease and its treatments, changes to the family daily routine and related limitations are among the main characteristics of the first months after the diagnosis. Close contact with the rheumatology team helps with the problems related to methotrexate application and side effects. We will review the parents' perspective of the treatment with its positives and negatives and will share our current feelings as well as our worries regarding her long-term prospects. The patient and family views expressed in a structured manner using a health-related quality of life instrument (CHAQ, JAMAR) have become an important part of overall JIA assessment. <h3>Disclosure of Interest</h3> None Declared
RT-12 * OUTCOMES IN MEDULLOBLASTOMA: SINGLE INSTITUTION CASE SERIES
Authors: V. Kannan, R. Bajpai, V. Anand, S. Deshpande, B. K. Misra, A. Kapadia, S. Almel, M. Sankhe, K. Desai, A. Kannan, S. Dubey, P. P. Ashok, S. Shinde
Journal: Neuro-Oncology (2014)

BACKGROUND: We have seen a paradigm shift in terms of use of radiation technology for the treatment of patients with medulloblastoma, from conventional 2-D shifting fields to 3-D CRT, IMRT and proton therapy. Similarly from prone to supine position and reduced dose to the cranio-spinal axis with an intent to have equivalent outcomes with reduced probability of late sequelae including second malignancies. METHODS: We have analysed data of 21 consecutive patients in May 2014, registered and treated in our hospital between 2002 and 2011. The cohort consisted of 14 male and 7 female patients with a median age of 8 (Range 3-30) Years. With no known co-morbidities and median KPS of 70 they all had tumors mostly in the IV ventricle(43%) and cerebellum(38%), for which they underwent surgery including decompression(72%) subtotal excision(9%), near total or total excision(19%). All patients were histologically grade IV medulloblastoma who underwent adjuvant radiation alone (40%) or followed by chemotherapy (60%) based on the risk stratification. 57% received 3D CRT in supine position while rest are treated with conventional techniques, median dose given to cranio-spinal axis was 23.4 Gy, posterior fossa was 36 Gy and to the tumor bed was 55.8 Gy at 1.8Gy per fraction. Chemotherapy was usually procarbazine/cisplatin/vincristine based regimen. Regular IQ, endocrine, ophthalmic and auditory evaluation was done in all the patients on follow-up. RESULT: Overall survival at 5 year was documented at 45% and 10 year survival at 35% for the entire cohort taking worst case scenario.3/13 patients developed IQ problems, 7/13 developed endocrine dysfunction, 3/12 developed auditory abnormality. CONCLUSION: Outcome of this cohort is comparable to the literature on risk group stratification. More importantly, risk adapted strategy for the treatment was found to be technically and logistically feasible and effective for a comparatively rare tumor in our setup.
Abstract 3666: Follicle-stimulating hormone inhibits apoptosis and autophagy in ovarian cancer cells by activating survivin and Rab25
Authors: Yingtao Liu, Yan Huang, Hongyan Jin, Kwai Wa Cheng, Yiling Lu, Yinhua Yu, Youji Feng
Journal: Cancer Research (2010)

Abstract Follicle-stimulating hormone (FSH) has been demonstrated to increase the risk of ovarian malignancy, but the mechanisms remains unclear. Our previous results showed that FSH increases the expression of VEGF through activation of survivin, which is mediated by the activation of the PI3K/AKT signaling pathway. We reported, herein, that FSH promoted ovarian cancer cells proliferation and prevented apoptosis in vitro and in vivo. FSH up-regulated the expression of survivin and down-regulated the expression of programmed cell death 6 (PDCD6) and death receptor 5 (DR5), two molecules required for apoptosis induction. Further, we have defined that the decreased expression of DR5, but not PDCD6, was mediated by survivin. We have established animal xenografts tissue arrays, the tumors from the groups with FSH treatment had higher expression of survivin and lower expression of DR5 comparing with the tumors from untreated groups, further confirming the interaction of FSH-survivin-DR5. In addition, we have demonstrated that FSH does not only inhibit apoptosis, but also inhibit autophagy. FSH inhibits autophagy by activating mTOR pathway in ovarian cancer cells under different stress conditions, including serum starvation. By Reverse Phase Protein Arrays (RPPA) analysis and western blot confirmation, we found that FSH stimulation increases the level of Rab25 in multiple ovarian cancer cells in a dose dependent manner. Rab25, a small GTPase, is found to be associated with the progression of ovarian tumor. Rab25, belongs to Rab11 supfamily, was shown to involve in endosomal recycling. To study the role of FSH-Rab25 interaction in regulating autophagy, we knocked down Rab25 expression in ES-2, Hey and SKOv3 ovarian cancer cell lines by siRNA, and examined the effects of FSH on autophagy. Rab25 knockdown increased the starvation induced autophagy through the inhibition of pAkt, while FSH administration could partly reverse the effects of Rab25 knockdown, due to the increase of Rab25 expression stimulated by FSH. Our findings indicated that Rab25 is one of the molecules regulated by FSH in ovarian cancer cells that has a novel role as a regulator in autophagy. Taken together, we have demonstrated that FSH promotes ovarian cancer development through regulating expression of survivin, Rab25, PDCD6 and DR5, which in turn regulates cell proliferation, apoptosis as well as autophagy. Further understanding the molecular mechanisms of FSH in the process of ovarian carcinogenesis and development will ultimately help developing an effective cancer prevention method, and find a novel targeted therapy for ovarian cancer. 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 3666.
Abstract P2-14-01: A Prospective Controlled Analysis of Fertility Preservation by Oocyte and Embryo Cryopreservation Using an Aromatase Inhibitor-Gonadotropin Protocol: Treatment Outcomes and Safety in Young Women with Breast Cancer
Authors: K Oktay, SH Lee, F Moy
Journal: Cancer Research (2010)

Abstract Objective: Breast Cancer (BCa) is the most common malignancy in reproductive age women and letrozole, an aromatase inhibitor, has been used to reduce estrogen exposure in women undergoing embryo/oocyte cryopreservation prior to chemotherapy. Our aim was to determine the long-term outcomes and safety of letrozole-FSH protocol. Design: Prospective Materials and Methods: Women with stage 0-3 BCa underwent ovarian stimulation with letrozole 5-mg starting menstrual cycle day (CD)-2 and gonadotropins 150-450 IU, starting CD-4. Oocyte maturation was triggered either with human chorionic gonadotropin (hCG) or a Gonadoropin Releasing Hormone Agonist (GnRHa). Results: Of the 129 women with mean age of 35.2±4.6, 13 vs. 91 underwent oocyte vs. embryo freezing, and 9 underwent both. Ovarian trigger with GnRHa (n=37/115, 32.2%) resulted in higher number of mature oocytes (10.9±6.6 vs. 8.4±6.0, p=0.045,). Of those, 21 underwent 25 frozen embryo transfers (mean age 35.5±4.5) with a clinical pregnancy (CP) rate of 68% and y per ET. CP rates were similar between the self-transfer and gestational carrier groups (7/9 vs. 10/16, p=0.37). No birth defects are encountered. Relapse rates were compared to a similar group of women with BCa (n=141, mean age 35.7±4.7, similar projected 10-year relapse rate at the outset by! adjuvant online) who elected to not to undergo ovarian stimulation. After a mean follow up of 2.4±1.6 vs. 2.9±1.7 years (range 8 mo - 5.6y vs. 4m-6.8y) women who had undergone ovarian stimulation with letrozole and FSH had a significantly lower recurrence rate [2.0% vs. 25.0%, Hazard ratio 0.08, 95%C.I. (0.06, 0.48), p=0.01]. Conclusions: This long term follow up of LF protocol for up to 7 years indicates that the protocol is safe, efficient and is associated with age-appropriate pregnancy success rates. Whether pretreatment with letrozole improves BCa treatment outcomes should be further investigated. Women with BCa can be safely offered this protocol when undergoing fertility preservation prior to chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-14-01.
343 HUMAN HEPATOCYTE INDOLEAMINE-2,3-DIOXYGENASE CONTRIBUTES TO ANTIVIRAL DEFENSE AND IMMUNE REGULATION IN HEPATITIS C VIRUS INFECTION
Authors: Q. Lepiller, E. Soulier, M. Lambotin, J. Barths, P. Bachellier, F. Stoll-Keller, T.F. Baumert, T.J. Liang, H. Barth
Journal: Journal of Hepatology (2013)
Enhancement of Sensitivity of Human Squamous Carcinoma Cells to Radiation by Epidermal Growth Factor
Authors: T T Kwok, R M Sutherland
Journal: JNCI Journal of the National Cancer Institute (1989)

Experiments were done to determine the effect of murine epidermal growth factor (EGF) on the radiation responses of the human squamous carcinoma cell line CaSki grown as an exponential monolayer culture. The radiation responses studied induded recovery from potentially lethal damage (PLDR) and recovery from sublethal damage (SLDR). The presence of EGF in the cell culture either after irradiation (during the clonogenic assay period) or continuously before, during, and after irradiation enhanced the radiosensitivity of the cells and reduced their plating efficiency (PE). However, these effects were not as great when EGF was present in the cell culture only before and during irradiation. This enhancement of radiosensitivity was associated with a reduction in the shoulder region of the cell survival curves. The PE reduction and radiosensitivity enhancement were maximum with 10 ng of EGF/mL However, EGF present continuously in the cell culture, induding during the 6-hour repair period, had no effect on cellular PLDR or SLDR. The single-stranded DNA breaks present in large numbers in cells immediately after irradiation returned to control levels by 6 hours. Moreover, EGF present in cell cultures for the 48 hours before irradiation and during the 6-hour repair period had no effect on the DNA alkaline elution profiles of either control or irradiated cells. EGF did not affect the growth of unirradiated cells; however, it extended the lag-phase period for growth of irradiated cells. In summary, this EGF-induced radiosensitivity enhancement was not correlated with the effects of EGF on PE, cell growth, PLDR, or SLDR.
Tips for a Physician in Getting the Right Job, Part XIII
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2014)

Part of how an applicant is judged is by the quality of questions he/she asks. If the answers to the questions could be readily found with minimal research, that does not give a good impression. Failure to ask good questions can be viewed as a lack of knowledge, preparation, or interest. If the candidate asks many questions about finances and vacations during the opening minutes of an interview, without inquiring about the practice, that also does not give a good impression. On the other hand, during the later phases of an interview day(s), questions regarding remuneration, call, and time off should be asked.
Amiodarone to Prevent Recurrence of Atrial Fibrillation
Authors: Denis Roy, Mario Talajic, Paul Dorian, Stuart Connolly, Mark J. Eisenberg, Martin Green, Teresa Kus, Jean Lambert, Marc Dubuc, Pierre Gagné, Stanley Nattel, Bernard Thibault
Journal: New England Journal of Medicine (2000)

The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial.
FRI0408 Rituximab treatment reduces circulating th2 cells and il4 expression in the skin of patients with systemic sclerosis.
Authors: I. Antonopoulos, S.-N. Liossis, D. Daoussis, A. Tsamandas, T. Markatseli, E. Karatza, A. Drosos, A. Andonopoulos
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Evidence suggests that B cells play a key role in the pathogenesis of Systemic Sclerosis (SSc). B cell depletion therapy has been used in the treatment of SSc with favorable results in lung function and skin fibrosis. However its mechanism of action remains to be elucidated. <h3>Objectives</h3> We investigated the effect of RTX on T-helper 1 (Th1), T-helper 2 (Th2) and T-helper 17 (Th17) cells as well as on serum cytokines, aiming at exploring the potential mechanisms of action of RTX. <h3>Methods</h3> We assessed 14 patients with SSc prior to and 6 months following RTX administration and 3 patients with SSc on standard treatment at the same time points. CD4 cells were separated from peripheral blood, stimulated with PMA and Ionomycin, stained for intracellular cytokines and measured using Flow Cytometry. Th1, Th2 and Th17 cells were defined as CD4 cells stained positive for Interferonγ (INFγ), Interleukin 4 (IL4) and Interleukin 17 (IL17) respectively. Serum levels of IL4 were measured by employing a quantitative ELISA method. IL4 expression in the skin was assessed using immunohistochemistry in skin biopsies obtained from 12 patients with SSc prior to and 6 months following RTX treatment and 3 control SSc patients. Immunohistochemical assessment was performed using computerized image analysis. Statistical analysis was performed by employing the paired t-test. Results were expressed as mean ± SEM. <h3>Results</h3> We found a significant decrease in circulating Th2 cells in all 14 patients following RTX treatment (mean±SEM: 13.9±4.2% vs 9.3±3.7 prior to and following RTX administration respectively, p=0.016). RTX had no effect on Th1 (mean±SEM: 3.47±0.68 vs 2.79±0.93 prior to and following RTX administration respectively, p=NS) and Th17 cells (mean±SEM: 0.25±0.07 vs 0.19±0.04 prior to and following RTX administration respectively, p=NS). We found no changes in serum levels of IL4 in all 14 patients. The 3 patients who were not treated with RTX exhibited no differences in Th1, Th2 and Th17 cells. A decrease in IL4 expression in the skin was small but significant in all 12 patients following RTX treatment both in the papillary (mean±SEM: 1.95±0.28% vs 1.15±0.164 prior to and following RTX administration respectively, p=0.004) and the reticular dermis of the skin (mean±SEM: 1.78±0.26 vs 1.15±0.15 prior to and following RTX administration respectively, p=0.008) while no differences were found in IL4 expression in the skin of controls. Immunostaining for IL4 was almost exclusively found in skin infiltrating mononuclear cells. <h3>Conclusions</h3> Our study shows that RTX reduces circulating Th2 cells and IL4 expression in the skin. Th2 cells are currently thought as strongly related with fibrosis. Further studies on the mechanisms of RTX action in patients with SSc are warranted. <h3>Disclosure of Interest</h3> None Declared
AB0463 Tofacitinib Improves Arterial Stiffness with Methotrexate-Resistant Active Rheumatoid Arthritis. A Cohort Study
Authors: K. Kume, K. Amano, S. Yamada
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk. We should have strategies for primary cardiovascular prevention in RA. Tofacitinib (Tofa) could possibly play a role in up-regulating levels of serum cholesterol<sup>1</sup>. But there is no evidence of CV risk management about Tofa. <h3>Objectives</h3> To examine the effect of Tofa plus methotrexate (MTX) on arterial stiffness in MTX resistant RA patients in a cohort study design. <h3>Methods</h3> 18 RA patients with moderate to severe active disease despite MTX treatment (disease activity score: DAS28&gt;3.2) were received Tofa plus MTX. All patients have no previous history of CV. Arterial stiffness was assessed with cardio-ankle vascular index (CAVI) and augmentation index corrected for a heart rate of 75 beats per minute (AIx@75) at baseline and 24 weeks follow-up. Clinical data were collected at regular visits. CAVI is very similar to pulse wave velocity (PWV), and CAVI measures arterial wall stiffness independent of blood pressure and it is superior to brachial ankle PWV as an index of arterial stiffness<sup>2</sup>. <h3>Results</h3> Treatment with Tofa (10.68±1.77 and 9.48±1.28%; p=0.016), attenuated the CAVI significantly from baseline to 24 weeks follow up. Treatment with Tofa (36.7±8.6, 32.2±3.6%; p=0.018) attenuated the Aix@75 significantly from baseline to 24 weeks follow up. DAS 28-ESR score improved significantly from baseline to 24 weeks (5.11±1.33, 2.43±1.43: p=0.01). On the other hand, fasting serum total cholesterol TC was significantly increased from baseline to follow-up at 24 weeks (211±21.2mg/dL, 232±24.2mg/dL, p=0.03). <h3>Conclusions</h3> These findings suggest that combination therapy, Tofa with MTX not only reduced RA disease activity but also limited vascular damage in patients with MTX resistant active RA. <h3>References</h3> Kremer J. et al. Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis: a randomized trial. Ann Intern Med. 2013 Aug 20;159(4):253-61. Takaki A et al. Cardio-ankle vascular index is superior to brachial-ankle pulse wave velocity as an index of arterial stiffness. Hypertens Res.2008 Jul; 31(7):1347-55 <h3>Acknowledgements</h3> We thank for Hiroshi Komori and Hiroyuki Ohta at Hiroshima Clinic for aquiring data. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1019
Absorption and Excretion of Four Penicillins
Authors: Clarke G. McCarthy, Maxwell Finland, Clare Wilcox, Joan H. Yarrows
Journal: New England Journal of Medicine (1960)

THE first of the semisynthetic penicillins to be prepared and exploited for clinical use after the isolation of pure 6-aminopenicillanic acid from penicillin fermentations1 is the potassium salt of the mixture of the D and L isomers of 6-(alpha-phenoxypropionamido) penicillanate or phenoxyethyl penicillin, also designated BRL1522 or P152DL3 and now given the generic name phenethicillin.§ On the basis of observations made by the manufacturers and some of their collaborators,2 , 4 , 5 one of the major advantages claimed for this new form of penicillin, and featured in all the advertisements of this product, is that molecular-equivalent doses for oral administration produce serum concentrations . . .
Abstract 3484: CTC enumeration and molecular characterization in a Phase 1 study of IGF-1 and IGF-2 inhibition by MEDI-573.
Authors: Xiaoru Chen, Xiaoqing (Sarah) Shi, Haifeng Bao, Theresa M. LaVallee, Dirk B. Mendel, Patricia A. Burke
Journal: Cancer Research (2013)

Abstract MEDI-573 selectively binds to human insulin-like growth factor (IGF)-1 and IGF-2 and inhibits ligand-mediated signal transduction via the insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor A isoform (IR-A) pathways, without perturbing glucose homeostasis. As IGF-1, IGF-2, and IGF-1R are overexpressed in bladder cancer, a Phase 1 expansion study including 20 bladder cancer subjects along with 6 additional subjects with other types of cancers from the dose escalation study were included for circulating tumor cell (CTC) analysis as part of a larger 42-subject study (MI-CP184) evaluating PK, safety, and biomarkers. Our objective for the results reported here was to evaluate CTC numbers as a prognostic indicator and as a biomarker of response to MEDI-573 therapy, and to evaluate the expression of IGF-1R on CTC and any correlation with treatment. Subjects in the expansion study were treated with MEDI-573 at 5 mg/Kg weekly (QW) (n=10), 15 mg/Kg QW (n=10), whereas subjects evaluated for CTC in the dose escalation study were treated at 30 or 45 mg/Kg every 3 weeks (Q3W) (n=3 each). CTC collected at screening and pre-dosing each cycle were enumerated and evaluated for IGF-1R expression by CellSearch®. 92% of subjects had at least one CTC at any time during the study and 62.5% had at least one CTC at screening. As has been demonstrated with other tumor types, subjects with ≤3 CTC at screening stayed on study longer than subjects with &amp;gt;3 CTC (2.3 vs. 1.2 months, P=0.0125 [no censoring]). Mean overall survival (OS) was also longer for subjects with ≤3 CTC compared to subjects with &amp;gt;3 CTC (6.37 vs. 2.83 months (P=0.0218, t test), although Kaplan-Myer curves were not different (P=0.0854)). Subjects with decreased numbers of CTC or no change in CTC with treatment stayed on study longer (not significant, P=0.0512, t test) than subjects with increased CTC with treatment (2.95 vs. 1.70 months). 73.3% (11/15) of subjects with positive CTC at screening had at least 1 CTC positive for IGF-1R. In conclusion, our results provide evidence for the utility of CTC as prognostic indicators in a Phase 1 study. Citation Format: Xiaoru Chen, Xiaoqing (Sarah) Shi, Haifeng Bao, Theresa M. LaVallee, Dirk B. Mendel, Patricia A. Burke. CTC enumeration and molecular characterization in a Phase 1 study of IGF-1 and IGF-2 inhibition by MEDI-573. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3484. doi:10.1158/1538-7445.AM2013-3484
Protracted neurotoxicity from chlordane sprayed to kill termites.
Authors: K H Kilburn, J C Thornton
Journal: Environmental Health Perspectives (1995)

Over 250 adults and children were exposed to chlordane when the wooden building surfaces and soil around an apartment complex were sprayed in 1987. Two hundred-sixteen adults had neurobehavioral functions measured and completed questionnaires for symptom frequency, mood status, confounding factors, and medical, rheumatic, and respiratory disorders in 1994. Measurements included simple and choice reaction time, balance, blink reflex latency, color vision, cognitive, perceptual motor, memory, and recall functions. We analyzed 216 exposed and 174 referent adults. Age, educational level, weight, height, and gender ratio were similar for the exposed and referent groups. Performance of balance, reaction times, Culture Fair, digit symbol, verbal recall, and trail-making were significantly impaired in exposed persons compared to referents. Mood-state scores were elevated, as were the frequencies of respiratory, neurobehavioral, and rheumatic symptoms. In contrast, long-term memory function was similar in both groups, consistent with its status before exposure. There was no identified bias or confounding factors. Chlordane exposure was associated with protracted impairment of neurophysiological and psychological functions. The central nervous system is the most important target of chlorinated cyclodiene insecticides. Human exposure should be prohibited.