tbuckley/cabot-search huggingface dataset:
A Model of Postsurgical Advanced Metastatic Breast Cancer More Accurately Replicates the Clinical Efficacy of Antiangiogenic Drugs
Authors: Eric Guerin, Shan Man, Ping Xu, Robert S. Kerbel
Journal: Cancer Research (2013)

Abstract The failure rate of randomized phase III oncology clinical trials is extremely high, even when preceded by encouraging preclinical studies and phase II trial results of the same therapy. Thus, there is considerable effort being made to improve the predictive clinical potential of preclinical models, in addition to improving phase II trial design. With respect to the former, preclinical models have historically relied heavily on treatment of primary spontaneous or transplanted tumors rather than the more common and therapeutically challenging clinical trial circumstance of advanced metastatic disease. Here, we show that the oral antiangiogenic tyrosine kinase inhibitor (TKI), sunitinib, which failed to meet primary or secondary survival endpoints in 4 separate phase III metastatic breast cancer (MBC) trials, either alone or with chemotherapy, similarly failed to show monotherapy or combination chemotherapy efficacy in a model of postsurgical advanced MBC using a metastatic variant of the MDA-MB-231 triple-negative human breast cancer. In contrast, the drug was effective when used to treat established orthotopic primary tumors. Similar results were obtained with pazopanib monotherapy, another antiangiogenic oral TKI. However, when an antibody targeting the VEGF pathway (DC101) was tested, it showed a trend in modestly improving the efficacy of paclitaxel therapy, thus resembling to a degree prior phase III clinical results of bevacizumab plus paclitaxel in MBC. Our results suggest the potential value of treating postsurgical advanced metastatic disease as a possible strategy to improve preclinical models for predicting outcomes in patients with metastatic disease. Cancer Res; 73(9); 2743–8. ©2013 AACR.
Induction in vivo and in vitro of terminal deoxynucleotidyl transferase by thymosin in bone marrow cells from athymic mice.
Authors: N H Pazmiño, J N Ihle, A L Goldstein
Journal: The Journal of Experimental Medicine (1978)

Terminal deoxynucleotidyl transferase (TdT) expression in bovine serum albumin (BSA) gradient-fractionated bone marrow cells was examined in NIH Swiss nu/nu and thymectomized C57BL/6 mice. In nude mice, TdT levels were approximately 10% of those of thymus-bearing littermates. In C57BL/6 mice, thymectomy caused a time-dependent loss of TdT activity in bone marrow cells. To determine whether or not not the apparent thymic requirement for TdT expression in bone marrow was mediated by thymic hormones, we examined the effects of thymosin fraction 5. Treatment of either NIH Swiss nu/nu or thymectomized C57BL/6 mice with thymosin fraction 5 restored the levels of TdT activity in BSA gradient-fractionated bone marrow cells to normal. Moreover, treatment of BSA gradient-fractionated bone marrow cells from NIH Swiss nu/nu or thymectomized C57BL/6 mice in tissue culture with thymosin fraction 5 induced TdT expression. In tissue culture, TdT induction was optimal with 25 ng/ml of thymosin fraction 5, it occurred within 6 h, and it was completely inhibited by actinomycin D. The effect was specific in that neither control nor spleen fraction 5-treated cells were induced to express TdT. These data demonstrate that TdT expression in bone marrow cells is under the direct control of thymic polypeptide hormones.
Incidence of renal failure and nephroprotection by RAAS inhibition in heterozygous carriers of X-chromosomal and autosomal recessive Alport mutations
Authors: Johanna Temme, Frederick Peters, Katharina Lange, Yves Pirson, Laurence Heidet, Roser Torra, Jean-Pierre Grunfeld, Manfred Weber, Christoph Licht, Gerhard-Anton Müller, Oliver Gross
Journal: Kidney International (2012)
Paneth cell-derived interleukin-17A causes multiorgan dysfunction after hepatic ischemia and reperfusion injury
Authors: Sang Won Park, Mihwa Kim, Kevin M. Brown, Vivette D. D'Agati, Thomas H. Lee
Journal: Hepatology (2011)

Abstract Hepatic ischemia and reperfusion (IR) injury is a major clinical problem that leads to frequent extrahepatic complications including intestinal dysfunction and acute kidney injury (AKI). In this study we aimed to determine the mechanisms of hepatic IR-induced extrahepatic organ dysfunction. Mice subjected to 60 minutes of hepatic IR not only developed severe hepatic injury but also developed significant AKI and small intestinal injury. Hepatic IR induced small intestinal Paneth cell degranulation and increased interleukin-17A (IL-17A) levels in portal vein plasma and small intestine. We also detected increased levels of IL-17A messenger RNA (mRNA) and protein in Paneth cells after hepatic IR with laser capture dissection. IL-17A-neutralizing antibody treatment or genetic deletion of either IL-17A or IL-17A receptors significantly protected against hepatic IR-induced acute liver, kidney, and intestinal injury. Leukocyte IL-17A does not contribute to organ injury, as infusion of wildtype splenocytes failed to exacerbate liver and kidney injury in IL-17A-deficient mice after hepatic IR. Depletion of Paneth cell numbers by pharmacological (with dithizone) or genetic intervention (SOX9 flox/flox Villin cre+/− mice) significantly attenuated intestinal, hepatic, and renal injury following liver IR. Finally, depletion of Paneth cell numbers significantly decreased small intestinal IL-17A release and plasma IL-17A levels after liver IR. Conclusion: Taken together, the results show that Paneth cell-derived IL-17A plays a critical role in hepatic IR injury and extrahepatic organ dysfunction. Modulation of Paneth cell dysregulation may have therapeutic implications by reducing systemic complications arising from hepatic IR. (Hepatology 2011;)
Kielland's forceps: role of antenatal factors in prediction of use.
Authors: D K James, M L Chiswick
Journal: BMJ (1979)

The association between certain antenatal factors and the use of Kielland9s forceps was analysed retrospectively in liveborn singleton births that occurred at this hospital between January and December 1976. Factors significantly associated with the use of Kielland9s forceps were primiparity, short maternal stature, induction of labour, late engagement of the fetal head, low ratio of maternal height to fetal occipitofrontal head circumference, slow dilatation of the cervix in labour, and the use of epidural analgesia in labour. The findings support a contribution of cephalopelvic disproportion in the genesis of malposition, and when associated with slow dilatation of the cervix delivery should be expedited. Long-term follow-up studies are needed, however, before the role of caesarean section in reducing morbidity associated with malposition can be properly assessed.
Tacrine in Alzheimer's Disease
Authors: René Dom
Journal: JAMA (1993)

<h3>To the Editor.</h3> —It seems unlikely that the recently published trial of tacrine<sup>1</sup>will solve the controversy that surrounds its use in Alzheimer's disease. Indeed, although the study is labeled as a straightforward parallel-group, double-blind comparison, the published analysis raises so many questions that the issue of the clinical value of tacrine remains unsettled. Excluding 195 (42%) of 468 patients raises several statistical questions. The comparison between the treatment groups should have been based on the 273 patients instead of on all patients, as was done. The conclusion from the study pertains to only 37 patients in the 80-mg tacrine group: too few to allow clinically relevant conclusions. It is debatable whether a comparison with placebo could be based on only 37 of the 78 patients who should have constituted this group according to randomization (468÷6=78). The reasons for excluding patients relate to the study medication. Therefore, the results
P140 Uptake and completion of pulmonary rehabilitation: the influence of referral source
Authors: A. L. Clark, K. A. Ingram, R. P. Fowler, P. Marns, S. S. C. Kon, J. L. Canavan, W. D. C. Man
Journal: Thorax (2011)

<h3>Background</h3> Pulmonary rehabilitation (PR) leads to significant improvements in exercise capacity, health status and dyspnoea in patients with chronic respiratory disease, supported by a strong evidence base. Despite the known benefits of PR, a proportion of referred patients never attend while others fail to complete the programme. The doctor-patient relationship is complex and may influence uptake and adherence to therapy. We hypothesised that uptake and completion of PR would be greater in patients referred from a senior doctor (hospital consultant or GP) compared with those referred by junior doctors or allied health professionals. <h3>Methods</h3> 466 consecutive referrals to the Pulmonary Rehabilitation (PR) programme were divided according to referral source: Senior Doctor (Hospital consultant or GP), Junior Doctor (Any trainee doctor from hospital or primary care) and Allied Health Professional (AHP: typically community/practice nurses or hospital physiotherapists). Uptake (proportion of referrals that start PR), and completion (proportion of patients that attended more than 8 PR sessions and the post-course assessment) were calculated for each referral source and compared using χ<sup>2</sup> test. <h3>Results</h3> Overall uptake and completion rates were 78% and 75% respectively (raw data Abstract P140 table 1). Uptake was significantly greater in referrals from Senior Doctor compared with Junior Doctor or AHP (82% vs 67% and 74% respectively; χ<sup>2</sup> p=0.02), although no significant difference was seen in completion (77% vs 70% and 68%; χ<sup>2</sup> p=0.25). Abstract P140 table 1 shows the raw data. There was no significant difference in baseline patient characteristics between the referral sources (age, FEV<sub>1</sub>%, MRC dyspnoea score, Hospital Anxiety and Depression score, incremental shuttle walk distance, Chronic Respiratory Disease Questionnaire, Lung Information Needs Questionnaire or COPD Assessment Test). <h3>Conclusion</h3> There is increased uptake of PR in patients referred by a hospital consultant or GP than if referred by a junior doctor or AHP. Further work is required to explore the reasons for this observation.
Distinct Roles of Autophagy in the Heart During Ischemia and Reperfusion
Authors: Yutaka Matsui, Hiromitsu Takagi, Xueping Qu, Maha Abdellatif, Hideyuki Sakoda, Tomoichiro Asano, Beth Levine, Junichi Sadoshima
Journal: Circulation Research (2007)

Autophagy is an intracellular bulk degradation process for proteins and organelles. In the heart, autophagy is stimulated by myocardial ischemia. However, the causative role of autophagy in the survival of cardiac myocytes and the underlying signaling mechanisms are poorly understood. Glucose deprivation (GD), which mimics myocardial ischemia, induces autophagy in cultured cardiac myocytes. Survival of cardiac myocytes was decreased by 3-methyladenine, an inhibitor of autophagy, suggesting that autophagy is protective against GD in cardiac myocytes. GD-induced autophagy coincided with activation of AMP-activated protein kinase (AMPK) and inactivation of mTOR (mammalian target of rapamycin). Inhibition of AMPK by adenine 9-beta-d-arabinofuranoside or dominant negative AMPK significantly reduced GD-induced autophagy, whereas stimulation of autophagy by rapamycin failed to cause an additive effect on GD-induced autophagy, suggesting that activation of AMPK and inhibition of mTOR mediate GD-induced autophagy. Autophagy was also induced by ischemia and further enhanced by reperfusion in the mouse heart, in vivo. Autophagy resulting from ischemia was accompanied by activation of AMPK and was inhibited by dominant negative AMPK. In contrast, autophagy during reperfusion was accompanied by upregulation of Beclin 1 but not by activation of AMPK. Induction of autophagy and cardiac injury during the reperfusion phase was significantly attenuated in beclin 1(+/-) mice. These results suggest that, in the heart, ischemia stimulates autophagy through an AMPK-dependent mechanism, whereas ischemia/reperfusion stimulates autophagy through a Beclin 1-dependent but AMPK-independent mechanism. Furthermore, autophagy plays distinct roles during ischemia and reperfusion: autophagy may be protective during ischemia, whereas it may be detrimental during reperfusion.
Echinocyte‐stomatocyte transformation and shape control of human red blood cells: Morphological aspects
Authors: Walter H. Reinhart, Shu Chien
Journal: American Journal of Hematology (1987)

Abstract Red cell morphology was studied after the induction of echinocytic transformation by metabolic depletion, Ca 2+ loading, and salicylate and stomatocytic transformation with chlorpromazine. The results indicate that the red cell has an energy‐dependent shape control mechanism that allows it to counteract shape‐changing stimuli such as metabolic depletion. Albumin was found to induce stomatocytic transformation, whereas γ‐globulins induced echinocytic transformation. Loading of the red cell with calcium resulted in polymorphous membrane damages such as submembranous, “blister‐like” lesions, and membrane disintegration; the red cell age had no influence on this process. Conversely, the stomatocyte‐echinocyte transformation induced by chlorpromazine and salicylate was shifted towards echinocytes in density‐separated old red cells. Sphero‐stomatocytes were capable of echinocytic transformation with spicule formation within the red cell vacuoles, whereas sphero‐echinocytes were unable to undergo stomatocytic transformation without hemolysis. These observations may help to unravel the complexity of echinocyte‐stomatocyte transformation of red blood cells.
Certain Clinical Characteristics Correlated with Extent of Obstructive Lesions Demonstrated by Selective Cine-Coronary Arteriography
Authors: WILLIAM L. PROUDFIT, EARL K. SHIREY, WILLIAM C. SHELDON, F. MASON SONES
Journal: Circulation (1968)

The duration of the history of angina pectoris, the distribution of the pain, the factors precipitating the pain, and serum cholesterol levels in the men less than the age of 40 years were studied in a group of 337 patients who had angina pectoris. Also the number of obstructed coronary arteries in 588 patients with severe obstruction in a larger study group of which the 337 patients were a part was compared with the number in men less than 40 years of age with severe lesions. The distribution of coronary arterial obstructions shown by selective cine-coronary arteriography was determined in relation to the clinical characteristics mentioned, and they were found to be of little predictive value. In most patients who had congestive heart failure occurring in the absence of recognized complications, multiple severe arterial obstructions were found. Division of patients who have anginal syndrome into groups on the basis of duration of history cannot clarify the natural history of symptomatic obstructive coronary arterial disease.
Health workers need information from countries with better health indicators than Britain and the US
Authors: A. Sekikawa, R. E Laporte, T. Satoh, G. Ochi
Journal: BMJ (1997)

Editor—Meeting the information needs of public health workers in developing countries is an urgent problem.1 Information has to be provided, but how best can this be done? The first public health institutions were established in England in the 19th century after the health effects of the Industrial Revolution were experienced. The advances in public health there had a strong influence in Europe and the United States. The approaches towards public health in the 20th century have been dominated by Britain and the United States. …
Diagnostic accuracy of esophageal capsule endoscopy versus conventional upper digestive endoscopy for suspected esophageal squamous cell carcinoma
Authors: D. Heresbach, E. Leray, P. d’Halluin, F. Cholet, M. Lapalus, M. Gaudric, E. Ben Soussan, J. Gaudin, K. Vahedi, V. Quentin, B. Filoche, J. Saurin, S. Chaussade, T. Ponchon
Journal: Endoscopy (2010)

A video capsule similar to that used in small-bowel capsule endoscopy is now available for esophageal exploration. The aim of our study was to compare the accuracy of upper endoscopy (esophageal gastroduodenoscopy [EGE]) with esophageal capsule endoscopy (ECE) in patients at risk of esophageal squamous cell cancer (SCC).68 patients at risk of SCC secondary to a history of head and neck neoplasia were included in this comparison of techniques for detecting SCC and dysplasia. ECE was done using the first generation Pillcam ESO and EGE was performed in accordance with the usual practice of each center, followed by examination with 2 % Lugol staining and biopsy of unstained areas (39 neoplasia comprising 5 low grade dysplasia, 8 high grade dysplasia and 26 SCC).Compared with EGE with and without Lugol staining, the sensitivities of ECE for neoplasia diagnosis were 46 % and 54 %, respectively. On a per-patient basis, the sensitivity, specificity, and positive and negative predictive value of ECE were 63 %, 86 %, 77 % and 76 %, respectively, compared with EGE without staining, and 61 %, 86 %, 77 % and 73 % compared with EGE with iodine staining. Neither the ECE transit time nor the distance between the esopharyngeal line and the neoplastic lesion differed between the 21 false-negative and 18 true-positive cases diagnosed by ECE; the only difference was a smaller median diameter among false negatives ( P < 0.001).In a cohort at high risk for esophageal SCC, ECE is not sensitive enough to diagnose neoplastic lesions.
The Aminopyrine Breath Test and Serum Bile Acids Reflect Histologic Severity in Chronic Hepatitis
Authors: Paul S. Monroe, Alfred L. Baker, John F. Schneider, Patricia S. Krager, Peter D. Klein, Dale Schoeller
Journal: Hepatology (2007)

To determine whether the aminopyrine breath test (ABT) and serum bile acid concentrations reflect histologic severity of chronic hepatitis, 56 patients were prospectively evaluated with liver biopsies and ABTs, and the results were compared to results of standard liver chemistry tests; 44 of these patients also had fasting and 2-hr postprandial serum bile acid measurements. Mean values for the ABT were significantly lower, and serum bile acids were significantly higher in patients with chronic active hepatitis with bridging or cirrhosis than in patients with mild chronic active hepatitis or chronic persistent hepatitis. Thirty of 35 patients with bridging or cirrhosis had ABTs less than 5.7% (mean of controls -2 S.D.) and 21 of 25 with mild chronic active hepatitis or chronic persistent hepatitis had values greater than 5.7% (sensitivity 0.86, specificity 0.84). Fasting and 2-hr postprandial bile acids were also more sensitive than standard chemistries in identifying patients with bridging or cirrhosis. Thus, the ABT and serum bile acids reflect histologic severity in chronic hepatitis patients and may be helpful in selecting patients for liver biopsy.
The Human Body Revealed
Authors: Daniel Engber
Journal: BMJ (2005)

An exhibition at the National Museum of Health and Medicine, Washington DC, until June 2005. Admission free http://nmhm.washingtondc.museum/exhibits/revealed/index.html Rating: ![Graphic][1]</img>![Graphic][2]</img> F or this exhibition artists have tried to create a model of the human body by combining real images with hand-drawn pictures, to “show the body, not as medical illustrations, but as it actually is.” That is to say, the artists have taken anatomical data from magnetic resonance imaging, computed tomography, and electron microscopy, reconstructed it in three dimensions, and then added colour, shadows, and shapes by hand. The result, they say, “is the art in science: to turn science into art.” The images come from the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
Associations Between Lipoproteins and the Progression of Coronary and Vein-Graft Atherosclerosis in a Controlled Trial With Gemfibrozil in Men With Low Baseline Levels of HDL Cholesterol
Authors: Mikko Syvänne, Markku S. Nieminen, M. Heikki Frick, Heikki Kauma, Silja Majahalme, Vesa Virtanen, Y. Antero Kesäniemi, Amos Pasternack, Christian Ehnholm, Marja-Riitta Taskinen
Journal: Circulation (1998)

Background —Lipid-lowering secondary-prevention trials of coronary artery disease (CAD) have implicated triglyceride-rich lipoproteins as the main determinants of angiographic progression after elevated LDL cholesterol levels have been lowered with therapy. The present study focuses on the lipoprotein determinants of angiographic CAD progression in men with low HDL cholesterol concentration as their main baseline lipid abnormality who underwent 32 months of randomized therapy with gemfibrozil or placebo. Methods and Results —Men who had undergone coronary bypass surgery (n=372) completed a randomized, placebo-controlled study with gemfibrozil 1200 mg/d. They were selected primarily for HDL cholesterol levels that corresponded to the lowest third for middle-aged men. Average baseline lipid and lipoprotein levels were serum triglyceride, 1.60; serum cholesterol, 5.17; ultracentrifugally separated LDL cholesterol, 3.43; HDL 2 cholesterol, 0.41; and HDL 3 cholesterol, 0.61 mmol/L. In the gemfibrozil group, these levels were reduced on average by 40%, 9%, and 6% or increased by 5% and 9%, respectively. On-trial IDL and LDL triglyceride and cholesterol levels significantly predicted global angiographic progression, taking into account changes in native segments and in bypass grafts. HDL 3 but not HDL 2 cholesterol concentration was associated with protection against progression, especially focal disease in native coronary lesions. VLDL was the lipoprotein most predictive of new lesions in vein grafts; IDL was also significantly related. Conclusions —This study expands the previous evidence of the triglyceride-rich lipoproteins, especially IDL, as predictors of angiographic progression of CAD but does not negate the significance of mildly elevated LDL levels. Of the HDL subfractions, only HDL 3 was protective in this group of men selected for their low initial HDL levels.
Potential health and environmental effects of trace elements and radionuclides from increased coal utilization.
Authors: R I Van Hook
Journal: Environmental Health Perspectives (1979)

This report addresses the effects of coal-derived trace and radioactive elements. A summary of our current understanding of health and environmental effects of trace and radioactive elements released during coal mining, cleaning, combustion, and ash disposal is presented. Physical and biological transport phenomena which are important in determining organism exposure are also discussed. Biological concentration and transformation as well as synergistic and antagonistic actions among trace contaminants are discussed in terms of their importance in mobility, persistence, availability, and ultimate toxicity. The consequences of implementing the President's National Energy Plan are considered in terms of the impact of the NEP in 1985 and 2000 on the potential effects of trace and radioactive elements from the coal fuel cycle. Areas of needed research are identified in specific recommendations.
Hyperlipidaemia advances and retreats.
Authors: J Revill
Journal: BMJ (1980)

treating underlying disease or at affecting mood and an understanding emotional support.Having said all this, one must still welcome the study by Bungay et al as a carefully executed and well presented account of the verbal aspects of the folkloric expression of the menopause in southern Britain and the pool of "middle-age symptoms" from which they are chosen.
631 ASSESSMENT OF SERUM HCV-RNA AT WEEK 12 POST-TREATMENT IS AS RELEVANT AS WEEK 24 TO PREDICT SVR IN HCV PATIENTS RECEIVING PEGINTERFERON PLUS RIBAVIRIN
Authors: M. Martinot-Peignoux, C. Stern, M.P. Ripault, L. Leclere, N. Boyer, P. Marcellin
Journal: Journal of Hepatology (2009)