tbuckley/cabot-search huggingface dataset:
Discussion about switch strategy in the adjuvant hormonal therapy of breast cancer: psychological aspects of physician–patient communication
Authors: A. Costantini, A. Picardi, M. Zilli, F. Cairoli, R. Torta, P. Marchetti, W. Baile, S. Iacobelli
Journal: Annals of Oncology (2009)

A survey of oncologists was conducted in Italy to evaluate the potential problems of physician-patient discussion about hormonal switch in the adjuvant therapy of breast cancer.A questionnaire, including both closed and open-ended questions, was administered to 70 oncologists. Fifty-one of them returned completely filled questionnaires.Forty-seven percent of the physicians reported difficulties in proposing the hormonal switch, and 60% stated that they found it difficult to make the therapeutic change acceptable to patients. The oncologist's barriers to propose the switch were related mostly to scientific and economic issues, such as the lack of certain advantages of aromatase inhibitors over tamoxifen (28%), their costs (14%) and their side-effects (34%). On the other hand, according to physicians, the patient's barriers to accept the therapeutic change were mainly due to psychological-relational factors, in particular the anxiety produced by the change (40%) and the bad patient-physician communication experienced in the past (26%).Patient-physician communication difficulties about switch strategy in the adjuvant hormonal treatment of breast cancer are, at least in part, related to psychological and relational factors. It is likely that training programs, improving doctor's communication skills, can overcome these problems.
DEVELOPMENTAL ASPECTS AND FACTORS INFLUENCING THE SYNTHESIS AND STATUS OF ASCORBIC ACID IN THE PIG
Authors: D.C. Mahan, S. Ching, K. Dabrowski
Journal: Annual Review of Nutrition (2004)

Ascorbic acid synthesis in the pig occurs at mid-pregnancy, but activity of the enzyme l-gulono-gamma-lactone oxidase (GLO) declines thereafter during gestation and remains low when the pig nurses the sow. During late gestation the ascorbic acid concentration in the fetus increases, but serum and liver ascorbic acid concentration in the sow declines without affecting the dam's liver GLO activity. It is presumed that as gestation progresses an increased amount of maternal ascorbic acid is transferred to the fetus and to the mammary gland. Colostrum and milk are rich sources of the vitamin and supply the nursing pig with ascorbic acid. The available data suggest that high amounts of ascorbic acid appear to suppress liver GLO activity in the pig. Upon weaning, when exogenous vitamin C is generally not provided, liver GLO activity and serum ascorbic acid increases. During the initial periods postweaning, some reports have indicated growth benefits of supplemental vitamin C. Body tissues differ in their concentrations of ascorbic acid, but tissues of high metabolic need generally have greater concentrations. The corpus luteum in the female, the testis in the male, and the adrenal glands in all pigs contain greater concentrations of the vitamin. Knockout genes preventing ascorbic acid synthesis in pigs have demonstrated poor skeletal and collagen formation and poor antioxidant protection. Under periods of stress ascorbic acid declines in the adrenal, but the pig rapidly recovers to its resting state once the stressor agent is removed. Although there are periods when supplemental vitamin C has been shown to promote pig performance (e.g., during high environmental stress and early postweaning), supplemental vitamin C has not been shown to routinely enhance pig performance.
Reduced Expression of Cyclooxygenase-2 in Primary Breast Cancer
Authors: Eva-Maria Boneberg, Daniel F. Legler, Hans-Jörg Senn, Gregor Fürstenberger
Journal: JNCI Journal of the National Cancer Institute (2008)

tumor-adjacent tissues, and healthy breast tissues, we performed real-time RT – PCR analysis and normalized the expression of COX-2 to the mean expression of four different housekeeping genes. The expression of COX-2 mRNA was decreased in the breast cancer samples (mean COX-2 expression: 0.3, 95% confi dence interval [CI] = 0.2 to 0.4) in comparison with tumor-adjacent tissues (mean expression: 2.0, 95% CI = 1.3 to 2.7) and healthy tissues (mean expression: 1.0, 95% CI = 0.5 to 1.4) ( Figure 1 ). The median expression of COX-2 in tumor tissues was only 20% of the median expression in healthy tissues ( P < .001) and only 10% of that of tumor-adjacent tissues ( P < .001). Furthermore, none of the tumor samples with relative high COX-2 expression exceeded the range of COX-2 expression found in healthy tissue samples or tumoradjacent samples. Some tumor samples showed only about 1% of the mRNA levels measured in tumor-adjacent tissues. Our results indicate that COX-2 is expressed at reduced levels in human breast cancer, not overexpressed as previously reported. Furthermore, we did not fi nd any correlation of COX-2 mRNA expression in the tumor tissues with the mRNA expression of HER2/neu, estrogen receptor alpha, or the progesterone receptor (data not shown). The loss of COX-2 expression in established breast cancers that we observed could explain the failure of celecoxib to inhibit tumor growth in the cited clinical trial ( 1 ).
Evaluation of Dimebon in cellular model of Huntington's disease
Authors: Jun Wu, Qin Li, Ilya Bezprozvanny
Journal: Molecular Neurodegeneration (2008)

Dimebon is an antihistamine compound with a long history of clinical use in Russia. Recently, Dimebon has been proposed to be useful for treating neurodegenerative disorders. It has demonstrated efficacy in phase II Alzheimer's disease (AD) and Huntington's disease (HD) clinical trials. The mechanisms responsible for the beneficial actions of Dimebon in AD and HD remain unclear. It has been suggested that Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.We evaluated the effects of Dimebon in experiments with primary striatal neuronal cultures (MSN) from wild type (WT) mice and YAC128 HD transgenic mice. We found that Dimebon acts as an inhibitor of NMDA receptors (IC50 = 10 muM) and voltage-gated calcium channels (IC50 = 50 muM) in WT and YAC128 MSN. We further found that application of 50 muM Dimebon stabilized glutamate-induced Ca2+ signals in YAC128 MSN and protected cultured YAC128 MSN from glutamate-induced apoptosis. Lower concentrations of Dimebon (5 muM and 10 muM) did not stabilize glutamate-induced Ca2+ signals and did not exert neuroprotective effects in experiments with YAC128 MSN. Evaluation of Dimebon against a set of biochemical targets indicated that Dimebon inhibits alpha-Adrenergic receptors (alpha1A, alpha1B, alpha1D, and alpha2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon also had significant effect on a number of additional receptors.Our results suggest that Ca2+ and mitochondria stabilizing effects may, in part, be responsible for beneficial clinical effects of Dimebon. However, the high concentrations of Dimebon required to achieve Ca2+ stabilizing and neuroprotective effects in our in vitro studies (50 muM) indicate that properties of Dimebon as cognitive enhancer are most likely due to potent inhibition of H1 histamine receptors. It is also possible that Dimebon acts on novel high affinity targets not present in cultured MSN preparation. Unbiased evaluation of Dimebon against a set of biochemical targets indicated that Dimebon efficiently inhibited a number of additional receptors. Potential interactions with these receptors need to be considered in interpretation of results obtained with Dimebon in clinical trials.
New Antithrombotic Drugs: Potential for Use in Oncology
Authors: Mark N. Levine
Journal: Journal of Clinical Oncology (2009)

For more than 50 years, heparin and vitamin K antagonists (VKAs) have been the anticoagulant drugs used to prevent and treat thrombosis. Low molecular weight heparins (LMWHs) are more recent and have been available for approximately 20 years. Patients with cancer are members of a unique patient population because of their high risk for thrombosis and the risk of anticoagulant-related bleeding. With the currently available antithrombotic agents, patients with cancer still have unmet needs in terms of the prevention and treatment of thrombosis. Although long-term LMWH is the treatment of choice for patients with cancer who have acute, symptomatic venous thromboembolism (VTE), some patients still experience recurrent VTE. More effective antithrombotic agents are needed for such patients. Convenient (ie, oral and with no laboratory monitoring), effective, and safe agents are needed to prevent thrombosis in patients taking chemotherapy and antiangiogenic drugs and in patients with central vein catheters. There are a number of new antithrombotic agents that have been studied in recent years and will soon be available for certain diseases. They target either activated factor X (ie, factor Xa) or activated thrombin, and some of them have potential therapeutic value in patients with cancer. In this article, the clinical research model used for the development of a new antithrombotic agent is discussed along with the results of recent trials that evaluate these new agents in high-risk populations.
Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats.
Authors: M Muntzel, T Hannedouche, B Lacour, T Drüeke
Journal: Journal of the American Society of Nephrology (1992)

Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure (BP) increases during rHuEPO therapy, observed particularly in persons with a history of hypertension. To determine whether preexisting hypertension enhances BP increases to rHuEPO, BP responses to 2 wk of rHuEPO or placebo were observed in spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto [WKY] rats. In addition, the role of endothelial-released nitric oxide (NO) in BP alterations caused by rHuEPO through i.v. infusions of endothelium-dependent and independent vasoactive agents were indirectly examined. At trial completion, rHuEPO elevated hematocrit, hemoglobin, and mean cell volume more in SHR than in WKY rats (P less than 0.001). Despite the considerable increase in hematocrit, rHuEPO did not alter BP in either strain. An infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, elevated BP more in rHuEPO-treated SHR than in identically treated WKY rats (P less than 0.05). Further, the administration of L-arginine caused a greater decrease in blood pressure in SHR than in WKY rats, independent of treatment condition (P less than 0.01). Because changes in BP with endothelium-independent agents were similar across groups, responses to L-NMMA and L-arginine were specific to the endothelium and probably independent of basal BP. Thus, rHuEPO provoked greater erythropoiesis in SHR than in WKY rats but did not elevate BP. L-NMMA stimulated higher BP in SHR treated with rHuEPO, suggesting a compensatory increase in vasodilatory NO synthesis to protect against a hypertensive effect of the drug in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of meal temperature on gastric emptying of liquids in man.
Authors: W M Sun, L A Houghton, N W Read, D G Grundy, A G Johnson
Journal: Gut (1988)

Serial studies were carried out on six healthy volunteers (19-24 years) to investigate the effect of meal temperature [either 4 degrees C (cold), 37 degrees C (control) or 50 degrees C (warm)] on the rate of gastric emptying of a radiolabelled isosmotic drink of orange juice. The mean maximum intragastric temperature occurred 60 seconds after the onset of ingestion of the warm drink and reached 43.0 degrees C (0.4) mean (SD) while the mean minimum intragastric temperature occurred 45 seconds after the onset of ingestion of the cold drink and reached 21.2 degrees C (1.9). Intragastric temperature then returned to body temperature within 20-30 minutes of ingestion of the warm and cold drinks. Warm and cold drinks appeared to empty from the stomach more slowly than the control drink. The initial rate of gastric emptying of the cold drink was significantly slower than the control drink (p less than 0.05) and the difference in emptying rates between cold and control drinks were significantly correlated with the differences in intragastric temperatures (p less than 0.01). The difference in the initial emptying rates between warm and control drinks were not statistically significant.
<i>Helicobacter pylori</i> and gastro-oesophageal reflux disease: Information on underlying pathology is not given
Authors: Giovanni Cammarota, Giovanni B Gasbarrini
Journal: BMJ (2004)

EDITOR—We read with interest the article by Harvey et al on the effects of Helicobacter pylori infection on heartburn and gastro-oesophageal reflux.1 However, as the authors recognise, the mechanism by which H pylori infection might affect reflux …
Suppression of Peripheral Pain by Blockade of Voltage‐Gated Calcium 2.2 Channels in Nociceptors Induces RANKL and Impairs Recovery From Inflammatory Arthritis in a Mouse Model
Authors: Uta Baddack, Silke Frahm, Beatriz Antolin‐Fontes, Jenny Grobe, Martin Lipp, Gerd Müller, Ines Ibañez‐Tallon
Journal: Arthritis & Rheumatology (2015)

A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies inflammation and joint deformation. Patients with RA rate pain relief as the highest priority; however, few studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways. The ω-conotoxin MVIIA (ziconotide) is used in humans to alleviate persistent pain syndromes, because it specifically blocks the voltage-gated calcium 2.2 (CaV 2.2) channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The aims of this study were to investigate whether blockade of CaV 2.2 can suppress arthritis pain, and to examine the progression of induced arthritis during persistent CaV 2.2 blockade. Transgenic mice expressing a membrane-tethered form of MVIIA under the control of a nociceptor-specific gene (MVIIA-transgenic mice) were used in the experiments. The mice were subjected to unilateral induction of joint inflammation using a combination of antigen and collagen. CaV 2.2 blockade mediated by tethered MVIIA effectively suppressed arthritis-induced pain; however, in contrast to their wild-type littermates, which ultimately regained use of their injured joint as inflammation subsided, MVIIA-transgenic mice showed continued inflammation, with up-regulation of the osteoclast activator RANKL and concomitant joint and bone destruction. Taken together, our results indicate that alleviation of peripheral pain by blockade of CaV 2.2- mediated calcium influx and signaling in nociceptor sensory neurons impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV 2.2 channel blockers as analgesics during inflammation.
Anticipating disaster: the genetics of familial pancreatic cancer
Authors: M M Lerch
Journal: Gut (2006)

To be born into a family with familial pancreatic cancer, an inheritable, autosomal dominant disorder, has various implications for an individual's life--and none is fortunate. The prospects just turned even darker because of "anticipation", the phenomenon that successive generations are affected by an inheritable disorder at a progressively earlier age. An up to date study shows that "anticipation" is also operative in familial pancreatic cancer, meaning that affected children die approximately 10 years earlier than their affected parents.
Immunotherapy for Osteosarcoma: Genetic Modification of T cells Overcomes Low Levels of Tumor Antigen Expression
Authors: Nabil Ahmed, Vita S Salsman, Eric Yvon, Chrystal U Louis, Laszlo Perlaky, Winfried S Wels, Meghan K Dishop, Eugenie E Kleinerman, Martin Pule, Cliona M Rooney, Helen E Heslop, Stephen Gottschalk
Journal: Molecular Therapy (2009)

Human epidermal growth factor receptor 2 (HER2) is expressed by the majority of human osteosarcomas and is a risk factor for poor outcome. Unlike breast cancer, osteosarcoma cells express HER2 at too low, a level for patients to benefit from HER2 monoclonal antibodies. We reasoned that this limitation might be overcome by genetically modifying T cells with HER2-specific chimeric antigen receptors (CARs), because even a low frequency of receptor engagement could be sufficient to induce effector cell killing of the tumor. HER2-specific T cells were generated by retroviral transduction with a HER2-specific CAR containing a CD28.zeta signaling domain. HER2-specific T cells recognized HER2-positive osteosarcoma cells as judged by their ability to proliferate, produce immunostimulatory T helper 1 cytokines, and kill HER2-positive osteosarcoma cell lines in vitro. The adoptive transfer of HER2-specific T cells caused regression of established osteosarcoma xenografts in locoregional as well as metastatic mouse models. In contrast, delivery of nontransduced (NT) T cells did not change the tumor growth pattern. Genetic modification of T cells with CARs specific for target antigens, expressed at too low a level to be effectively recognized by monoclonal antibodies, may allow immunotherapy to be more broadly applicable for human cancer therapy.
Comparison of Corticotropin-Releasing Factor, Dexamethasone, and Temozolomide: Treatment Efficacy and Toxicity in U87 and C6 Intracranial Gliomas
Authors: Maxim A. Moroz, Ruimin Huang, Tatiana Kochetkov, Weiji Shi, Howard Thaler, Elisa de Stanchina, Idoia Gamez, Robert P. Ryan, Ronald G. Blasberg
Journal: Clinical Cancer Research (2011)

PURPOSE/EXPERIMENTAL DESIGN: Treatment of cerebral tumors and peritumoral brain edema remains a clinical challenge and is associated with high morbidity and mortality. Dexamethasone is an effective drug for treating brain edema, but it is associated with well-documented side effects. Corticorelin acetate (Xerecept) or human corticotrophin-releasing factor (hCRF) is a comparatively new drug and has been evaluated in two orthotopic glioma models (U87 and C6), by a direct comparison with dexamethasone and temozolomide.In vitro combination therapy and monotherapy showed a variable response in 6 different glioma cell lines. In vivo studies showed a dose-dependent effect of hCRF (0.03 and 0.1 mg/kg q12h) on survival of U87 intracranial xenograft-bearing animals [median survival: control--41 days (95% CI 25-61); "low-hCRF" 74.5 days (95% CI 41-88); "high-hCRF" >130 days (95% CI not reached)]. Dexamethasone treatment had no effect on survival, but significant toxicity was observed. A survival benefit was observed with temozolomide and temozolomide + hCRF-treated animals but with significant temozolomide toxicity. C6-bearing animals showed no survival benefit, but there were similar treatment toxicities. The difference in hCRF treatment response between U87 and C6 intracranial gliomas can be explained by a difference in receptor expression. RT-PCR identified CRF2r mRNA in U87 xenografts; no CRF receptors were identified in C6 xenografts.hCRF was more effective than either dexamethasone or temozolomide in the treatment of U87 xenografts, and results included improved prognosis with long-term survivors and only mild toxicity. The therapeutic efficacy of hCRF seems to be dependent on tumor hCRF receptor (CRFr) expression. These results support further clinical assessment of the therapeutic efficacy of hCRF and levels of CRFr expression in different human gliomas.
Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis
Authors: Jorge L. Gross
Journal: Annals of Internal Medicine (2011)

Background: Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. Purpose: To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. Data Sources: MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. Study Selection: Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A1c (HbA1c) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. Data Extraction: Primary end points were change in HbA1c level, change in weight, and frequency of severe hypoglycemia. Data Synthesis: Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA1c level (reduction ranging from −0.70% [95% credible interval {CrI}, −1.33% to −0.08%] for acarbose to −1.08% [CrI, −1.41% to −0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (−1.63 kg [CrI, −2.71 to −0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. Limitations: Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. Conclusion: There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patient's clinical characteristics. Primary Funding Source: Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenaçăo de Aperfeiçoamento de Pessoal de Nível Superior.
Computed tomographic scan–diagnosed chronic obstructive pulmonary disease–emphysema: Eotaxin-1 is associated with bronchodilator response and extent of emphysema
Authors: Marina Miller, Joe Ramsdell, Paul J. Friedman, Jae Youn Cho, Marian Renvall, David H. Broide
Journal: Journal of Allergy and Clinical Immunology (2007)
Effect of zopiclone on sleep, night-time ventilation, and daytime vigilance in upper airway resistance syndrome
Authors: F Lofaso, F Goldenberg, C Thebault, C Janus, A Harf
Journal: European Respiratory Journal (1997)

We have assessed the effects of zopiclone (7.5 mg), a new cyclopyrrolone hypnotic drug, on ventilation, sleep parameters, and daytime vigilance in snorers with upper airway resistance syndrome (UARS). Using a randomized double-blind design, eight male patients with UARS took either oral zopiclone or a placebo each evening for seven consecutive days and then crossed over to the other drug after a 7 day placebo period. Polysomnography followed by a multiple sleep latency test (MSLT) was performed during the last night of each treatment period. Zopiclone produced significant improvements in the sleep efficiency index (total sleep time/time in bed) (placebo 84+/-15% versus zopiclone 91+/-7%) and average MSLT (placebo 10.3+/-3.7 min versus zopiclone 14.9+/-2.8 min), as well as nonsignificant improvements in sleep onset latency and total sleep time. It had no effect on sleep architecture or on the arousal index (placebo 17+/-8 arousals x h(-1) versus zopiclone 17+/-4 arousals x h[-1]). Furthermore, none of the respiratory parameters were significantly affected by zopiclone. In conclusion, zopiclone has no adverse effects on sleep architecture, respiratory parameters during sleep, and daytime sleepiness in patients with UARS.