tbuckley/cabot-search huggingface dataset:
Inhibition of IκB phosphorylation in cardiomyocytes attenuates myocardial ischemia/reperfusion injury
Authors: Y ONAI, J SUZUKI, T KAKUTA, Y MAEJIMA, G HARAGUCHI, H FUKASAWA, S MUTO, A ITAI, M ISOBE
Journal: Cardiovascular Research (2004)

Objective: Reperfusion injury is related closely to inflammatory reactions such as activation of inflammatory cells and expression of cytotoxic cytokines. We investigated the efficacy of IκB phosphorylation blockade in a rat myocardial ischemia/reperfusion injury model. Methods and results: IMD-0354 inhibited phosphorylation of IκBα and nuclear translocation of nuclear factor-kappa B (NF-κB) induced by tumor necrosis factor-α (TNF-α) in cultured cardiomyocytes. TNF-α-induced production of interleukin-1β and monocyte chemoattractant protein-1 from cultured cardiomyocytes was reduced significantly by IMD-0354. Transient left coronary artery occlusion (30 min) and reperfusion (24 h) were carried out in Sprague–Dawley rats. IMD-0354 (1, 5, 10 mg/kg) was injected intraperitoneally 5 min before the start of reperfusion. Treatment with IMD-0354 resulted in a significant dose-dependent reduction of the infarction area/area at risk ratio (vehicle, 47.0±3.4%; 10 mg/kg of IMD-0354, 19.4±4.0%; P<0.01) and the preservation of fractional shortening ratio (vehicle, 25.0±1.5%; 10 mg/kg of IMD-0354, 42.3±1.7%; P<0.01). Histological analysis showed that accumulation of polymorphonuclear neutrophils in the area at risk was decreased significantly. Conclusions: Inhibition of nuclear translocation of NF-κB by IκBα phosphorylation blockade could provide an effective approach to attenuation of ischemia/reperfusion injury. The cardioprotective effects of IMD-0354 include not only reduction of harmful neutrophil accumulation in myocardium but also inhibition of harmful cytokine and chemokine production by cardiomyocytes.
Acute myelogenous leukemia in Chile PINDA protocols 87 and 92 results
Authors: J Quintana, P Advis, A Becker, V Beresi, M Campbell, E F Vinés, H García, C Salgado, L Vargas, J Rojas, M Obando, L Neira, E Páez, P Zolezzi
Journal: Leukemia (2005)
Reductions in Systemic and Skeletal Muscle Blood Flow and Oxygen Delivery Limit Maximal Aerobic Capacity in Humans
Authors: José González-Alonso, José A.L. Calbet
Journal: Circulation (2003)

A classic, unresolved physiological question is whether central cardiorespiratory and/or local skeletal muscle circulatory factors limit maximal aerobic capacity (VO2max) in humans. Severe heat stress drastically reduces VO2max, but the mechanisms have never been studied.To determine the main contributing factor that limits VO2max with and without heat stress, we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures (+10 degrees C and +1 degrees C). Heat stress reduced VO2max, 2-legged VO2, and time to fatigue by 0.4+/-0.1 L/min (8%), 0.5+/-0.2 L/min (11%), and 2.2+/-0.4 minutes (28%), respectively (all P<0.05), despite heart rate and core temperature reaching similar peak values. However, before exhaustion in both heat stress and normal conditions, cardiac output, leg blood flow, mean arterial pressure, and systemic and leg O2 delivery declined significantly (all 5% to 11%, P<0.05), yet arterial O2 content and leg vascular conductance remained unchanged. Despite increasing leg O2 extraction, leg VO2 declined 5% to 6% before exhaustion in both heat stress and normal conditions, accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis.These results demonstrate that in trained humans, severe heat stress reduces VO2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow, O2 delivery, and O2 uptake. Furthermore, the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle.
TCT-156 Impact of Clopidogrel Hyporesponsiveness on Clinical Outcomes in Patients Receiving Drug-eluting Stents for Stable Coronary Disease in the ADAPT-DES Study
Authors: Dietmar Trenk, Bruce R. Brodie, Heinz Joachim Büttner, David Cox, Peter L. Duffy, Timothy D. Henry, Ajay J. Kirtane, Ernest L. Mazzaferri, Roxana Mehran, D. Christopher Metzger, Gregg W. Stone, Thomas Stuckey, Giora Weisz, Bernhard Witzenbichler, Ke Xu, Franz-Josef Neumann
Journal: Journal of the American College of Cardiology (2013)
Observations on Dyspepsia arising from Disordered States of the Mind
Authors: W. D. Husband
Journal: BMJ (1841)

The different forms of animals," says the illus- trious Cuvier, " may be regarded as so many differenit kinids of experiments ready prepared by Nature, who adds to, or deducts from each, different parts, just as we might wish to do in our laboratories, showing us herself at the same time their different results."This beautiful remark of the Gallic Aristotle may be ex- tended to every grade of created objects.The in- crease of inorganic masses is effected by external agents, while themselves serve only as passive nuclei.The vegetable has a power, gradually becoming more perfect, as its organisation becomes more complex, assigned to it, by which it can take up food, and apply it to the nutritionl and development of its com- poinent organs.The wandering animal requires a
Sleep and drug overdose.
Authors: J M Macgregor
Journal: BMJ (1970)

storage of chemical products and increased publicity of the potential dangers of chemi- cal agents.6Legislation in Canada and the United States will shortly make safety con- tainers mandatory for drugs and household products.2I In November 1969 the Liverpool Regional Hospital Board agreed that the Palm-N-Turn container should be intro- duced into the region and that this programme should start in Birkenhead.It is hoped that child-resistant containers will be adopted in other areas and that their use may be made compulsory throughout the country as soon as possible.-Iam, etc.,
Exacerbation of coronary occlusion induced ventricular arrhythmias by the vagolytic effect of procainamide
Authors: P. B. CORR, C. J. HELKE, R. A. GILLIS
Journal: Cardiovascular Research (1978)

The influence of the vagolytic effect of procainamide on the early ventricular arrhythmias induced by left anterior descending coronary (LAD) occlusion was studied in chloraloseanaesthetised cats. All control animals developed a ventricular arrhythmia (1119 +/- 166 PVCs per hour), with a consistent onset time, duration, and overall mortality due to ventricular fibrillation (ie 20%). In 18 animals pretreated with procainamide (0.5 mg.kg-1.min-1 for 50 min), there was no effect on the ventricular arrhythmia in terms of ectopic frequency (1020 +/- 180 PVCs per hour), time to onset of arrhythmia, duration of arrhythmia, and mortality incidence (ie 16.7%). However, subdividing the data according to whether or not vagal blockade had been produced by procainamide revealed that animals exhibiting complete vagal blockade demonstrated significantly more ectopic beats (1606 +/- 310 PVCs per hour) and 33% developed ventricular fibrillation. Treated animals without complete vagal blockade exhibited an ectopic frequency rate of 620 +/- 98 PVCs per hour and none of the animals developed ventricular fibrillation. The haemodynamic parameters were similar between both procainamide treated subgroups. These results suggest that an important factor in response of the ischaemic heart to the cardiac rhythm effects of procainamide is the degree of vagal blockade induced by this agent.
Acute Renal Failure and Transient Hypercalcemia in Idiopathic Rhabdomyolysis
Authors: Charles D. Leonard
Journal: JAMA (1970)

Acute renal failure in association with idiopathic rhabdomyolysis developed in a 29-year-old man. Symptomatic hypercalcemia occurred during the diuretic period and was accompanied by hypercalciuria, elevated serum alkaline phosphatase level, decreased tubular reabsorption of phosphate, and an increased serum parathyroid hormone level. Transient hyperparathyroidism is suggested as the primary mechanism responsible for this unusual complication of acute renal failure and physicians are alerted to this potential hazard.
Unrelated donor bone marrow transplantation using a chemotherapy‐only preparative regimen for adults with high‐risk acute myelogenous leukemia
Authors: Lois J. Ayash, Voravit Ratanatharathorn, Thomas Braun, Samuel M. Silver, Christopher M. Reynolds, Joseph P. Uberti
Journal: American Journal of Hematology (2006)

Abstract Limited data are available for adults undergoing unrelated donor (URD) BMT for AML using chemotherapy‐only preparative regimens. Previous studies incorporated irradiation, included adults and children, and excluded secondary leukemia. Herein we report long‐term outcomes for adults with poor‐prognostic AML receiving a novel regimen of busulfan (16 mg/kg), cytarabine (8,000 mg/m 2 ), and cyclophosphamide (120 mg/kg) (BAC), followed by URD BMT. From June 1995 through October 2001, 45 adults were enrolled. Adverse features included unfavorable cytogenetics (49%), secondary AML (47%), leukemia at transplant (42%), and extramedullary disease (16%). At time of BMT, 23 were in remission (12 CR1) while 22 had leukemia. Four (9%) died early. Acute and chronic GVHD rates were 44 and 67%, respectively. Seventeen (38%) were disease‐free 52 months post‐BMT; 13 were leukemia‐free (eight CR1) at transplant. Eleven relapsed. Three‐year DFS and OS were 42 and 46%, respectively. DFS and OS were longer, and relapses less, for those in CR at time of BMT. Secondary leukemia, cytogenetics, cell dose, and GVHD did not influence outcome. In poor‐risk AML, BAC provided cytoreduction comparable to reported TBI‐containing regimens, when administered for URD BMT. With decreasing treatment‐related mortality, it is justified to proceed early to URD BMT for patients with poor prognostic features. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Radionuclide Imaging of the Liver in Human Fascioliasis
Authors: J.V. Rivera, R.H. Bermudez
Journal: Clinical Nuclear Medicine (1984)

The clinical, laboratory, and scintigraphic findings in four cases of human fascioliasis are described. Acute onset of fever, abdominal pain, and weight loss in a person who has ingested watercress constitutes the clinical syndrome often seen. Eosinophilia and alteration in liver function tests, particularly alkaline phosphatase are frequent. Tc-99m sulfur colloid images showed hepatomegaly in four patients, focal defects in two, splenomegaly in three, and increased splenic uptake in two. Gallium citrate (Ga 67) images show increased uptake in the focal lesions in two of two. Sonographic imaging showed focal lucent abnormality in one of three. Liver biopsy findings were nonspecific. The differential diagnosis from other invasive parasitic diseases is discussed. A possible role of hepatic imaging in the evaluation of fascioliasis is suggested.
Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement
Authors: D. J Llewellyn, I. A Lang, K. M Langa, F. Naughton, F. E Matthews
Journal: BMJ (2009)

<b>Objective</b> To examine the association between a biomarker of exposure to secondhand smoke (salivary cotinine concentration) and cognitive impairment. <b>Design</b> Cross sectional analysis of a national population based study. <b>Setting</b> Stratified random sample of households throughout England. <b>Participants</b> 4809 non-smoking adults aged 50 years or more from the 1998, 1999, and 2001 waves of the Health Survey for England who also participated in the 2002 wave of the English Longitudinal Study of Ageing and provided saliva samples for cotinine assay and a detailed smoking history. <b>Main outcome measure</b> Cognitive impairment as defined by the lowest 10% of scores on a battery of neuropsychological tests. <b>Results</b> Participants who did not smoke, use nicotine products, or have salivary cotinine concentrations of 14.1 ng/ml or more were divided into four equal size groups on the basis of cotinine concentrations. Compared with the lowest fourth of cotinine concentration (0.0-0.1 ng/ml) the odds ratios (95% confidence intervals) for cognitive impairment in the second (0.2-0.3 ng/ml), third (0.4-0.7 ng/ml), and highest fourths (0.8-13.5 ng/ml) were 1.08 (0.78 to 1.48), 1.13 (0.81 to 1.56), and 1.44 (1.07 to 1.94; P for trend 0.02), after adjustment for a wide range of established risk factors for cognitive impairment. A similar pattern of associations was observed for never smokers and former smokers. <b>Conclusions</b> Exposure to secondhand smoke may be associated with increased odds of cognitive impairment. Prospective nationally representative studies relating biomarkers of exposure to cognitive decline and risk of dementia are needed.
PELVIC INFLAMMATORY DISEASES.
Authors: A. H. CORDIER
Journal: JAMA (1898)

This subject would seem to be worn threadbare, judging from its being so often used as a theme for discussion, yet the fabric, being of great surgical value, has rather improved by use and age. The discussion of any topic in which the questions of human life and comfort are concerned is always timely and of interest. Sentiment and fashion should never be permitted to enter into a proposition where the question is one in which these unsurgical twins have long since proved themselves montrosities. Abdominal scars have been used as breastworks behind which some surgeons have hidden their fears of removing complications and the performance of complete work, while they made and abandoned tunnels in which the enemy threw up additional fortifications to repulse the invader who attempts to reduce their stronghold to liberate imprisoned organs and dislodge the offending cause. It is perfect surgery, or as near perfect
Transforming growth factor-β adaptor, β2-spectrin, modulates cyclin dependent kinase 4 to reduce development of hepatocellular cancer
Authors: Hye Jung Baek, Michael J. Pishvaian, Yi Tang, Tae Hyun Kim, Shaoxian Yang, Majed El Zouhairi, Jon Mendelson, Kirti Shetty, Bhaskar Kallakury, Deborah L. Berry, Kyung Hwan Shin, Bibhuti Mishra, Premkumar E. Reddy, Sang Soo Kim, Lopa Mishra
Journal: Hepatology (2010)

Abstract Transforming growth factor beta (TGF-β) is an important regulator of cell growth, and loss of TGF-β signaling is a hallmark of carcinogenesis. The Smad3/4 adaptor protein β2-spectrin (β2SP) is emerging as a potent regulator of tumorigenesis through its ability to modulate the tumor suppressor function of TGF-β. However, to date the role of the TGF-β signaling pathway at specific stages of the development of hepatocellular carcinoma (HCC), particularly in relation to the activation of other oncogenic pathways, remains poorly delineated. Here we identify a mechanism by which β2SP, a crucial Smad3 adaptor, modulates cyclin dependent kinase 4 (CDK4), cell cycle progression, and suppression of HCC. Increased expression of β2SP inhibits phosphorylation of the retinoblastoma gene product (Rb) and markedly reduces CDK4 expression to a far greater extent than other CDKs and cyclins. Furthermore, suppression of CDK4 by β2SP efficiently restores Rb hypophosphorylation and cell cycle arrest in G1. We further demonstrate that β2SP interacts with CDK4 and Smad3 in a competitive and TGF-β-dependent manner. In addition, haploinsufficiency of cdk4 in β2sp+/− mice results in a dramatic decline in HCC formation compared to that observed in β2spZ+/− mice. Conclusion : β2SP deficiency leads to CDK4 activation and contributes to dysregulation of the cell cycle, cellular proliferation, oncogene overexpression, and the formation of HCCs. Our data highlight CDK4 as an attractive target for the pharmacologic inhibition of HCC and demonstrate the importance of β2sp+/− mice as a model of preclinical efficacy in the treatment of HCC. (Hepatology 2011;)
Effects of hydrocortisone on the adrenaline-adenylate cyclase system of the skin
Authors: H. IIZUKA, K. KAMIGAKI, O. NEMOTO, T. AOYAGI, Y. MIURA
Journal: British Journal of Dermatology (1980)

Using pig skin slices, we investigated the effects of hydrocortisone on the adenylate cyclase system of the skin. In short-term experiments, hydrocortisone, when added singly or in combination with other stimulators of adenylate cyclase in the skin (adrenaline or histamine), had no effect on cyclic AMP accumulation. However, when skin slices were incubated with hydrocortisone for more than 6 h, the response to adrenaline differed, with a greater accumulation of cyclic AMP in the hydrocortisone-treated skin. This effect was seen at a concentration of more than I micrometer hydrocortisone and was most marked 48 h later, while responses to adrenaline in control skin gradually decreased and remained low. Histamine, which is another stimulator of adenylate cyclase of the skin, did not cause a greater cyclic AMP accumulation in response to this hydrocortisone treatment. There was no significant difference in either low Km or high Km cyclic AMP phosphodiesterase activities as a result of this hydrocortisone treatment. Hydrocortisone seems to act by protecting the adrenaline-adenylate cyclase system of the skin.
Hyperbaric Treatment of Subcutaneous Emphysema
Authors: Edgar End
Journal: JAMA (1967)

ABSTRACT To the Editor:— Kaplan and Barnes (JAMA202:153, 1967) described a case of subcutaneous emphysema and ischemia of the toes caused by accidental injection of helium under the skin. Their patient would have benefited from hyperbaric oxygen. The increased pressure would have compressed subcutaneous gas into less than half it original volume (Boyle's law) and thus would have relieved pressure on soft tissues. Inhalation of oxygen would have reduced blood nitrogen and minimized diffusion of this gas from blood into subcutaneous gas pockets. Compression of subcutaneous gas would have hastened its diffusion into the blood and out of the body, while increased oxygen in the blood would have improved oxygenation of ischemic areas. Rapid diffusion of helium because of its small molecule (Graham's law) would have facilitated escape of this gas. Finally, hyperbaric therapy might have rendered unnecessary any decompressing incisions.
Multivariate Analysis-Reply
Authors: Robert A. Lew
Journal: JAMA (1983)

<h3>In Reply.—</h3> We are indebted to the correspondents, for it was they who confirmed our report<sup>1</sup>that the patients with melanoma most likely to survive as a result of elective lymph node dissection (ELND) are those with primary lesions of intermediate thickness. We have further refined our initial observations and have identified a subset of patients within the intermediate-thickness category who often have regional metastases but not distant metastases. This subset of patients has melanomas composed of discretely nested epithelioid or small cells with fine granular cytoplasm.<sup>2</sup> In other words, the correspondents hold that ELND saves the majority of patients in the intermediate-thickness group, whereas we suggest that ELND may save only a small subset of such patients. The correspondents seem to share our concern<sup>3</sup>that they have exaggerated the proportion of clinical stage I patients with melanomas 1.51 through 3.99 mm thick who are saved by
Lancet withdraws research paper and warns authors about rules of "gift authorship"
Authors: C. Dyer
Journal: BMJ (2008)

The Lancet has retracted a paper by researchers at the Medical University of Innsbruck in Austria after an official investigation found that the clinical trial it reported had serious ethical and procedural flaws.

Austria’s Agency for Health and Food Safety says that the urologists who conducted the trial of stem cell treatment for stress incontinence in women failed to get proper ethical approval and neglected to adequately inform patients of the experimental nature of the procedures. In one case an insurance confirmation form seemed to have been forged.

“In our view, the conclusions of this official investigation pinpoint so many irregularities in the conduct of their work that, taken together, …
Improving aspirin prophylaxis after myocardial infarction in primary care: collaboration in multipractice audit between primary care audit group and health authority
Authors: K. Khunti, R. Sorrie, S. Jennings, A. Farooqi
Journal: BMJ (1999)

The Antiplatelet Trialists' Collaboration provided convincing evidence of benefits of aspirin prophylaxis in patients after myocardial infarction, 1 but many such patients do not receive it. 2 3Since most patients are followed up in primary care, practices need to implement methods of improving aspirin prophylaxis in these patients.The aim of this multipractice audit led by a primary care audit group was to assess and improve levels of prescribing of prophylactic aspirin for patients after myocardial infarction in Leicestershire.
3p Microsatellite Signature in Exhaled Breath Condensate and Tumor Tissue of Patients with Lung Cancer
Authors: Giovanna E. Carpagnano, Maria Pia Foschino-Barbaro, Antonio Spanevello, Onofrio Resta, Francesco Carpagnano, Giuseppina Mulé, Rosamaria Pinto, Stefania Tommasi, Angelo Paradiso
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Our group has recently demonstrated the possibility of studying microsatellite alterations (MAs) of 3p in the DNA of exhaled breath condensate (EBC) of patients with non-small cell lung cancer (NSCLC).To verify whether MAs analyzed in DNA from EBC reflect a profile of alterations present in tumor tissue of NSCLC.Fifty-nine subjects undergoing histologic diagnosis for clinical suspicion of lung cancer entered the study: 41 were found to have NSCLC and 18 to have nonneoplastic diseases. All subjects underwent allelotyping on DNA from whole blood, EBC, and lung tissue removed for histologic diagnosis by analyzing a panel of five microsatellites located in chromosomal region 3p. Results obtained from DNA of the three biological sites and nonneoplastic tissues from controls were compared.MAs in DNA from tumor tissues and EBC of each patient with cancer presented an overlapping profile of loss of heterozygosity and microsatellite instability. An MA profile of DNA of lung tissue reflecting the DNA of EBC profile from controls was also confirmed. Smoking status was associated with the presence of MAs in patients with NSCLC and in control subjects.We demonstrated that MAs in DNA from EBC of patients with NSCLC are significantly more frequent than in control subjects. More interesting, the MA profile of DNA from EBC corresponds to that from lung cancer tissue of each patient with NSCLC.
Synchrotron radiation-based Fourier-transform infrared spectromicroscopy for characterization of the protein/peptide distribution in single microspheres
Authors: Manli Wang, Xiaolong Lu, Xianzhen Yin, Yajun Tong, Weiwei Peng, Li Wu, Haiyan Li, Yan Yang, Jingkai Gu, Tiqiao Xiao, Min Chen, Jiwen Zhang
Journal: Acta Pharmaceutica Sinica B (2015)

The present study establishes a visualization method for the measurement of the distribution and localization of protein/peptide constituents within a single poly-lactide-co-glycolide (PLGA) microsphere using synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR). The representative infrared wavenumbers specific for protein/peptide (Exenatide) and excipient (PLGA) were identified and chemical maps at the single microsphere level were generated by measuring and plotting the intensity of these specific bands. For quantitative analysis of the distribution within microspheres, Matlab software was used to transform the map file into a 3D matrix and the matrix values specific for the drug and excipient were extracted. Comparison of the normalized SR-FTIR maps of PLGA and Exenatide indicated that PLGA was uniformly distributed, while Exenatide was relatively non-uniformly distributed in the microspheres. In conclusion, SR-FTIR is a rapid, nondestructive and sensitive detection technology to provide the distribution of chemical constituents and functional groups in microparticles and microspheres.