tbuckley/cabot-search huggingface dataset:
OP21 The role of Toll like receptor-4 in the pathogenesis of hepatorenal syndrome in a Bile duct ligated model of cirrhosis in the rat
Authors: N Shah, D Dhar, F Mohamed, R Mookerjee, N A Davies, R Jalan
Journal: Gut (2010)

Introduction  Hepatorenal syndrome (HRS) is a frequent presenting complication in patients with cirrhosis and usually occurs with a superimposed infection/inflammation. It is associated with high morbidity and mortality. The pathogenesis of the HRS is not delineated. Toll like receptors (TLR9s) play an important role in the recognition of molecules derived from microbes, which upon stimulation leads to activation of NFkB and pro inflammatory cascade. We hypothesised that cirrhosis associated endotoxaemia primes the kidney resulting in upregulation of TLR4 making the kidney susceptible to further endotoxaemia.  Aim  The aims of this study were to determine whether (1) cirrhosis is associated with an upregulation of TLR4, NFkB and proinflammatory cytokines in the kidney and (2) whether selective decontamination would result in a reduction in TLR4 expression, attenuate NFkB and cytokines and make the kidneys less susceptible to further endotoxemic insult.  Method  Six groups of Sprague–Dawley rats were studied; n=6 in each group (Sham operated, Sham-operated+LPS; BDL (4 weeks), BDL+LPS (1 mg/kg); BDL+Norfloxacin and BDL+LPS+Norfloxacin. The Norfloxacin groups were pretreated with Norfloxacin, 20 mg/kg administered orally daily for 10 days. The animals were studied 3 h after administration of placebo or LPS. Blood was for collected for biochemistry and cytokines. Kidney was collected for protein expression of TLR4 and NFkBp65 on Western blot and immunohistochemistry.  Results  TLR4 and NFkBp65 protein expression was significantly upregulated in BDL rat kidney compared to sham (p=0.03 and 0.02), respectively, this increased further on LPS administration (p=0.02 and p=0.01). TLR4 was mainly localised in the proximal tubule and its brush border with ongoing apoptosis as evident by the presence of caspase-3 positivity on immunohistochemistry. Selective decontamination with Norfloxacin attenuated the inflammatory response by reducing the protein expression of TLR4 and NFkBp65 in BDL vs BDL group administered with LPS (p=0.02 and p=0.01). It also led to an improvement in the creatinine in BDL and BDL+LPS group administered Norfloxacin (p=0.02 and p=0.03), respectively. Norfloxacin ameliorated the kidney cytokine surge in BDL and BDL+LPS group (TNF p=0.09 and p=0.04, respectively).  Conclusion  Our data provide strong evidence indicating an important pathogenic role of TLR4 in mediating susceptibility to the development of HRS in an experimental model of cirrhosis following inflammation/infection. Selective gut decontamination attenuates this pathological inflammatory process and prevents renal failure induced by LPS. TLR4 antagonist may be a therapeutic target for HRS.
Long‐term excess mortality in takotsubo cardiomyopathy: predictors, causes and clinical consequences
Authors: Thomas Stiermaier, Christian Moeller, Katrin Oehler, Steffen Desch, Tobias Graf, Charlotte Eitel, Reinhard Vonthein, Gerhard Schuler, Holger Thiele, Ingo Eitel
Journal: European Journal of Heart Failure (2016)
Mechanisms underlying loss of reciprocal fusion gene expression in acute promyelocytic leukaemia: evidence for deletions on der(17) and complex rearrangements yielding novel fusion gene transcripts
Authors: C Walz, David Grimwade, S Saussele, A Weisser, M Lafage-Pochitaloff, A Hochhaus, C Schoch, S Schnittger, E Lengfelder, N C P Cross, R Hehlmann, A Reiter
Journal: Blood (2003)
Microrna-155 Regulates Cockroach Allergen Induced Cyclooxygenase-2 Expression in Airway Epithelium
Authors: Lipeng Qiu, Yufeng Zhou, Yilin Zhao, Danh Do, Heng Wang, Changjun Li, Xiaopeng Liu, Xu Cao, Mei Wan, Peisong Gao
Journal: Journal of Allergy and Clinical Immunology (2016)
Unexpectedly high survival rate in very poor prognosis stage III B breast cancer patients receiving cisplatin-based primary chemotherapy. A multicenter Italian study
Authors: M. T. Ionta, A. Scanu, F. Atzori, D. Vacca, A. Contu, A. Farris, V. Lorusso, S. Palmeri, L. Minerba, B. Massidda
Journal: Journal of Clinical Oncology (2004)

605 Background: Primary chemotherapy, as part of multimodality treatment, has become the standard of care for locally advanced breast cancer (LABC) to increase DFS, OS and conservative surgery. Stage III B is renowned as the worst of LABC, and despite appropriate therapy the majority of patients (pts) will experience distant metastases and death within 2–3 years. The optimal regimen and schedule of primary chemotherapy is uncertain. Aim of our study was to verify the efficacy of an original cisplatin-based regimen (PEV) in terms of response and survival. Methods: Between 1996 and 2001 72 consecutive III B pts were treated with primary chemotherapy: Cisplatin 50 mg/m2, Epirubicin 100 mg/m2, Vinorelbine 25 mg/m2 every 14 (44%) or 21 (66%) days for 4 (33%) or 6 (67%) cycles, followed by surgery, radiation, adjuvant CMF 1, 8 q28 x 6 cycles + - TAM. Median age was 50 y (29–70); 47% premenopausal; 75% T4 abc, 25% T4 d; 45% ER-; 69% PgR-; 46% Ki 67+; 40% G3; 87,5% clinical axillary nodes positive. Results: All patients underwent surgery ( 25% conservative); according to Sataloff's classification 28% had pCR (absence or minimal microscopic residual disease) and 72% had pTR (gross residual disease) in breast; 40% had complete clearance of axilla (pN0) and 60% had residual nodes metastases (pN+); 22% had pCR both in breast and axilla. At median follow up of 52 months (22–87) DFS and OS were 64% and 76% respectively, significantly higher in pCR(85%and 95%) (p= 0.02) and in pN0 (83%and 90%) (p= 0.01) than in pTR(56%and 69%) or in pN+(51%and 67%). Moreover, Kaplan-Meier estimates showed a significant difference in OS between 6 (85%) and 4 cycles ( 58%) (p= 0.04); no statistical difference was seen between q14 /q21 groups. Conclusions: Primary PEV regimen, as part of multimodality treatment, appears to be highly active in terms of pCR, conservative surgery and survival rates in IIIB breast cancer patients and cost-effective. No significant financial relationships to disclose.
Nitrous Oxide as a Psychedelic Drug
Authors: G J Wolcott, T N Hackett
Journal: New England Journal of Medicine (1970)

The author questions whether or not the physician is bound to warn the patient with a potential medical complication that the pregnancy if continued could be detrimental to her or the babys health.  Also is he bound to suggest and offer termination of the pregnancy in such cases even if not previously requested by the patient?  This especially applies to several serious diseases and disorders.  The final decision should be an informed one on the part of the pregnant patient.  Further efforts to alter her decision are not warranted unless the risk is of a very high degree.  The author considers it morally and ethically incorrect not to inform the patient of the risks involved and not to offer the option of early termination of the pregnancy when this is perm itted by law.
Pilot study of FLT-PET/CT uptake in ovarian cancer patients with biologic correlates
Authors: J. Deloia, S. D. Richard, R. P. Edwards, E. Elishaev, S. Mason, D. Shinde, J. J. Mountz, B. Bencherif
Journal: Journal of Clinical Oncology (2007)

16045 Background: New imaging modalities for ovarian cancer disease burden are needed. Positron emission tomography (PET) with [F-18] fluorodeoxyglucose (FDG) has shown promise for early prediction of outcome and response to therapy when compared to CT alone. Recent studies have suggested that 3’-fluoro-3’ [F-18] deoxythymidine (FLT) has a higher specificity than FDG. The objective of this study was to correlate FLT tracer uptake with different in vitro quantitation of cellular proliferation. Methods: Patients with suspected or know ovarian cancer and an elevated Ca 125 were recruited for this trial. These patients were injected with 5 mCi of [F-18]FLT intravenously as a slow bolus. After an uptake period of 60 minutes, patients were scanned for approximately 36 minutes by CT and then PET, and images were co- registered. Standardized uptake values (SUV) of both hot and cold areas were obtained and these lesions were biopsied at the time of surgery. Tissue was divided and used for Ki-67 proliferation index staining to determine mitotic index, RNA isolation for rt-PCR for thymidine kinase-1 (TK1) levels, and grown ex vivo for cell proliferation analysis. Univariate analysis was preformed using the student's t-test. Results: PET positive lesions were found to have a significantly increased mitotic index when compared to control lesions (0.134 vs. 0.004, p&lt;0.001). There were no significant differences in relative TK1 levels or ex vivo cell proliferation ability between PET positive and control lesions in the initial four patients. Conclusions: Increased mitotic index by Ki-67 staining correlates with increased FLT activity by PET scan, but not TK1 levels or DNA content. We will continue to explore this modality as compared to FDG-PET in patients with ovarian cancer. No significant financial relationships to disclose.
The use of forced oscillation technique (FOT) in assessment of airway obstruction and airtrapping in elderly COPD patients
Authors: Hoi Nam Tse, King Ying Wong, Ka Yan Wai, Kwok Sang Yee
Journal: European Respiratory Journal (2011)

Introduction:  Forced oscillation technique (FOT) is a new lung function measurement technique that may have a role in assessing elderly COPD patients.   Aim:  To evaluate the accuracy of FOT in assessment of airway obstruction and airtrapping in elderly COPD patients.   Methods:  Stable spirometry-confirmed elderly COPD subjects were recruited from Kwong Wah Hospital, Hong Kong from Jan 10 to Jan 11.  Subjects were assessed by both conventional plethysmography and FOT machine in the same visit. Airway obstruction was measured by FEV1%, Raw, Gaw while degree of airtrapping was measured by residual volume (RV), total lung capacity (TLC), inspiratory capacity (IC) and RV/TLC ratio. FOT parameters like frequency resonance (FRes), frequency dependence (FDep), resistance at 6Hz (R6Hz), average resistance (RAvr), average reactance (XAvr) were obtained. The FOT parameters were then compared with the plethysmography.   Results:  Totally, 106 patients were recruited. 93.1% were male with a mean age of 70.6±8.3 and FEV1 of 54.3±21.3. FOT correlates well with conventional plethysmography for measurement of airway resistance and airtrapping in elderly COPD patients. Among the FOT parameters, FRes showed the best correlation with FEV1 (r=0.608, p   Conclusion:  FOT is an accurate and convenient technique for assessment of airway obstruction and airtrapping in elderly COPD patients.
Evaluation of clinical markup with CT simulation in whole brain radiation therapy
Authors: Y. Wang, N. Makhani, M. Tsao
Journal: Journal of Clinical Oncology (2007)

2043 Background: Two types of clinical markup have been used for whole brain radiation therapy (WBRT), but the extent of dose coverage and sparing of the lens is unknown. This study is designed to evaluate clinical markup with CT simulation. Methods: CT simulation images of the brain from 20 random adult patients were included in this study. Two types of inferior field borders were generated to mimic the 2 types of clinical markup of WBRT: from superior orbital ridge (SOR) to tragus, and from SOR to inferior tragal notch (ITN). A field margin of 1 cm from contoured brain (along base of skull) was used in CT simulation, except near the orbital globe where 0.5 cm margin to eye shielding was used. Two opposed lateral fields with 6 MV photon were used to generate 3 WBRT plans in each patient: clinical markup with SOR to tragus, SOR to ITN, and CT simulation. Dose volume histograms of the brain and lens were generated. The primary end point was dose coverage of whole brain with clinical markup. The secondary end point was sparing of the lens. Results: Patients with clinical markup using SOR to tragus or SOR to ITN had significantly larger median brain volume receiving less than 95% of the prescribed dose, 37.0 mL and 7.8 mL (respectively) compared to CT simulation 0 mL (P &lt; 0.001). All patients with SOR to tragus and most patients (95%) with SOR to ITN clinical markup had underdosing in the regions of inferior frontal lobe, temporal lobe and posterior fossa. There was no significant difference in the dose to the lens between CT simulation and clinical markup using SOR to tragus (P = 0.18) or SOR to ITN (P = 0.90). Conclusions: Whole brain radiation therapy with clinical markup using either SOR to tragus or SOR to ITN results in underdosing at the inferior frontal lobe, temporal lobe and posterior fossa. Sparing of the lens is adequately achieved with clinical markup. No significant financial relationships to disclose.
Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice
Authors: Jason M. Aliotta, Mandy Pereira, Sicheng Wen, Mark S. Dooner, Michael Del Tatto, Elaine Papa, Laura R. Goldberg, Grayson L. Baird, Corey E. Ventetuolo, Peter J. Quesenberry, James R. Klinger
Journal: Cardiovascular Research (2016)

Extracellular vesicles (EVs) from mice with monocrotaline (MCT)-induced pulmonary hypertension (PH) induce PH in healthy mice, and the exosomes (EXO) fraction of EVs from mesenchymal stem cells (MSCs) can blunt the development of hypoxic PH. We sought to determine whether the EXO fraction of EVs is responsible for modulating pulmonary vascular responses and whether differences in EXO-miR content explains the differential effects of EXOs from MSCs and mice with MCT-PH.Plasma, lung EVs from MCT-PH, and control mice were divided into EXO (exosome), microvesicle (MV) fractions and injected into healthy mice. EVs from MSCs were divided into EXO, MV fractions and injected into MCT-treated mice. PH was assessed by right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. miR microarray analyses were also performed on all EXO populations. EXOs but not MVs from MCT-injured mice increased RV/LV + S, WT/D ratios in healthy mice. MSC-EXOs prevented any increase in RV/LV + S, WT/D ratios when given at the time of MCT injection and reversed the increase in these ratios when given after MCT administration. EXOs from MCT-injured mice and patients with idiopathic pulmonary arterial hypertension (IPAH) contained increased levels of miRs-19b,-20a,-20b, and -145, whereas miRs isolated from MSC-EXOs had increased levels of anti-inflammatory, anti-proliferative miRs including miRs-34a,-122,-124, and -127.These findings suggest that circulating or MSC-EXOs may modulate pulmonary hypertensive effects based on their miR cargo. The ability of MSC-EXOs to reverse MCT-PH offers a promising potential target for new PAH therapies.
Endometrial cancer patients’ assessment of the benefits of exercise
Authors: K. M. Gil, K. Basen-Engquist, J. Lukowski, D. Detterman, M. P. Hopkins, E. L. Jenison
Journal: Journal of Clinical Oncology (2009)

e20553 Background: Endometrial cancer patients remain at risk for other obesity related cancers and illnesses. Patients should be counseled to increase their physical activity, however, their belief concerning potential outcomes of exercise will affect how they are counseled. Methods: Patients treated for Stage I endometrial cancer with no other cancer diagnoses were asked if they had been exercising regularly for more than 6 months using the CDC definition of exercise (exercisers), how likely they thought regular exercise would result in health related outcomes (see Table ) and how important these outcomes are to them using Likert-like scales ranging from 1 to 5. A weighed calculation of how likely regular exercise would result in an outcome of importance to them was obtained by multiplying the two scores. Chi-square and t-tests were used to analyze data with SPSS V15. Results: 76 of 90 women approached completed the questionnaire (84%), mean age was 59.5 ± 1.1 (SEM). 45% were exercisers, their mean BMI was lower (31.2 ± 1.2 vs. 38.0 ± 1.4, p=0.001) and a non significantly lower proportion reported having diabetes (15% vs 26%) or hypertension (26% vs 43%). The majority of all women believed regular exercise would result in positive outcomes; a lower proportion of exercisers reported it very to extremely likely that regular exercise would reduce the risk of developing cancer (27% vs 54%, p=0.023) or osteoporosis (46% vs 73%, p=0.019). The majority reported these outcomes were very to extremely important to them; a lower proportion of exercisers reported reducing the risk of developing a new cancer or diabetes were (cancer 79% vs 98%, p=0.013; diabetes 78% vs 100%, p=0.003). Both groups believed feeling better physically and emotionally were important and likely consequences of exercise; exercisers were less likely to believe several other outcomes were important and likely consequences ( Table ). Conclusions: Women who exercise regularly and develop cancer may become disillusioned with the potential health benefits of exercise despite having improved health. [Table: see text] No significant financial relationships to disclose.
Role of Hormones in the Growth and Regression of Human Breast Cancer Cells (MCF-7) Transplanted Into Athymic Nude Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S M Shafie, F H Grantham
Journal: JNCI Journal of the National Cancer Institute (1981)

The hormonal environments require by human breast cancer cells MCF-7 to produce solid tumors in nude mice are described. A 100% take was obtained within 7 days following inoculation of 2X10(6) actively growing (log phase) MCF-7 cells into the mammary fat pads of intact, athymic BALB/c nude mice. Tumors failed to develop, even with an inoculum of 20X10(6) cells/mouse, in ovariectomized mice or in mice made diabetic with streptozotocin and observed for 90 days after cell inoculation. A 100% incidence of tumors was obtained in mice that were either hypophysectomized or made diabetic but received injections of 0.2 IU insulin/day/mouse. A 100% incidence of tumors was also obtained in ovariectomized mice that received 17 beta-estradiol in the form of a pellet placed subcutaneously in the interscapular region at the time of cell inoculation. Palpable tumors also developed in ovariectomized mice treated with prolactin, perphenazine, estrone, or estriol, but no takes were observed in ovariectomized mice treated with progesterone, 5 alpha-dihydrotestosterone, or hydrocortisone. Growth of the MCF-7 tumor was stimulated five- to sixfold in both intact and hypophysectomized mice that each received a 17 beta-estradiol pellet. Removal of the 17 beta-estradiol pellets form tumor-bearing ovariectomized mice failed to induce tumor regression. Tumors that continued to grow in ovariectomized mice deprived of 17 beta-estradiol regressed by 50% or more of their initial volume when tamoxifen was injected for 7 days at 5 micrograms/mouse/day) +/- theophyline (1 mg/mouse/day), tumor growth arrest was observed during the 2-to 3-week treatment period. Streptozotocin-induced diabetes in tumor-bearing mice always resulted in complete tumor regression following a 3-week treatment period.
The incidence of subsequent invasive ipsilateral and contralateral breast cancer in patients with lobular carcinoma in situ (LCIS)
Authors: S. Diab
Journal: Journal of Clinical Oncology (2005)

860 Background: Recent studies have indicated that patients with LCIS have higher incidence of ipsilateral breast cancer, suggesting that LCIS is a direct of invasive breast cancer. Methods: Patients with LCIS treated with breast conservation in the Surveillance, Epidemiology, and End Results (SEER) database who developed subsequent invasive breast cancer were analyzed according to the laterality of subsequent invasive breast cancer. Results: Of 5529 patients with LCIS, 447 developed subsequent invasive breast cancer (8.1%). 248 patients developed ipsilateral disease (4.5%) and 199 (3.6%) contralateral disease (p=0.01). The proportion of subsequent invasive lobular carcinoma in patients with LCIS was 40% compared to 10.8% incidence of invasive lobular in SEER overall. The patterns of second breast events for LCIS and ductal carcinoma in situ (DCIS) were similar. Conclusions: Similar to DCIS, LCIS should be regarded as a potential precursor lesion as well as a risk indicator. No significant financial relationships to disclose.
CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016
Authors: Deborah Dowell, Tamara M. Haegerich, Roger Chou
Journal: JAMA (2016)

Primary care clinicians find managing chronic pain challenging. Evidence of long-term efficacy of opioids for chronic pain is limited. Opioid use is associated with serious risks, including opioid use disorder and overdose.
Persistence of spermatozoa in the lower genital tracts of women
Authors: E. M. Silverman
Journal: JAMA (1978)

Cervicovaginal scrapings from 675 women who had volunteered information about the time of their last coitus and their contraceptive and douching practices were stained with Papanicolaou stain and screened for spermatozoa. Generally, as the interval between coitus and preparation of the smears (postcoital interval) increased, the percentage of smears with spermatozoa and the mean number of spermatozoa per smear decreased, but the percentage of spermatozoa with tails did not change significantly. Spermatozoa were found irregularly after the seventh and rarely after the tenth postcoital day. Vaginal douching, pregnancy, use of oral contraceptives, coitus interruptus, condoms, and vasectomy were associated with reduced prevalence of spermatozoa in smears. (<i>JAMA</i>240:1875-1877, 1978)
Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study
Authors: Elena H Martinez-Lapiscina, Sam Arnow, James A Wilson, Shiv Saidha, Jana Lizrova Preiningerova, Timm Oberwahrenbrock, Alexander U Brandt, Luis E Pablo, Simone Guerrieri, Ines Gonzalez, Olivier Outteryck, Ann-Kristin Mueller, Phillip Albrecht, Wesley Chan, Sebastian Lukas, Lisanne J Balk, Clare Fraser, Jette L Frederiksen, Jennifer Resto, Teresa Frohman, Christian Cordano, Irati Zubizarreta, Magi Andorra, Bernardo Sanchez-Dalmau, Albert Saiz, Robert Bermel, Alexander Klistorner, Axel Petzold, Sven Schippling, Fiona Costello, Orhan Aktas, Patrick Vermersch, Celia Oreja-Guevara, Giancarlo Comi, Letizia Leocani, Elena Garcia-Martin, Friedemann Paul, Eva Havrdova, Elliot Frohman, Laura J Balcer, Ari J Green, Peter A Calabresi, Pablo Villoslada
Journal: The Lancet Neurology (2016)