tbuckley/cabot-search huggingface dataset:
Phase II Trial of Gefitinib in Combination with Bevacizumab as First-Line Therapy for Advanced Non–Small Cell Lung Cancer with Activating EGFR Gene Mutations: The Okayama Lung Cancer Study Group Trial 1001
Authors: Eiki Ichihara, Katsuyuki Hotta, Naoyuki Nogami, Shoichi Kuyama, Daizo Kishino, Masanori Fujii, Toshiyuki Kozuki, Masahiro Tabata, Daijiro Harada, Kenichi Chikamori, Keisuke Aoe, Hiroshi Ueoka, Shinobu Hosokawa, Akihiro Bessho, Akiko Hisamoto-Sato, Toshio Kubo, Isao Oze, Nagio Takigawa, Mitsune Tanimoto, Katsuyuki Kiura
Journal: Journal of Thoracic Oncology (2015)
Efficient and Accurate Homologous Recombination in hESCs and hiPSCs Using Helper-dependent Adenoviral Vectors
Authors: Emi Aizawa, Yuka Hirabayashi, Yuzuru Iwanaga, Keiichiro Suzuki, Kenji Sakurai, Miho Shimoji, Kazuhiro Aiba, Tamaki Wada, Norie Tooi, Eihachiro Kawase, Hirofumi Suemori, Norio Nakatsuji, Kohnosuke Mitani
Journal: Molecular Therapy (2011)

Low efficiencies of gene targeting via homologous recombination (HR) have limited basic research and applications using human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Here, we show highly and equally efficient gene knockout and knock-in at both transcriptionally active (HPRT1, KU80, LIG1, LIG3) and inactive (HB9) loci in these cells using high-capacity helper-dependent adenoviral vectors (HDAdVs). Without the necessity of introducing artificial DNA double-strand breaks, 7-81% of drug-resistant colonies were gene-targeted by accurate HR, which were not accompanied with additional ectopic integrations. Even at the motor neuron-specific HB9 locus, the enhanced green fluorescent protein (EGFP) gene was accurately knocked in in 23-57% of drug-resistant colonies. In these clones, induced differentiation into the HB9-positive motor neuron correlated with EGFP expression. Furthermore, HDAdV infection had no detectable adverse effects on the undifferentiated state and pluripotency of hESCs and hiPSCs. These results suggest that HDAdV is one of the best methods for efficient and accurate gene targeting in hESCs and hiPSCs and might be especially useful for therapeutic applications.
Chlorpromazine and Agranulocytosis
Authors: J. Lomas
Journal: BMJ (1954)

<h3>PURPOSE</h3> To compare the efficacy of two nonionic T2*-shortening contrast agents, DyDTPA-BMA dysprodiamide injection and GdDTPA-BMA gadodiamide injection, as perfusion-sensitive MR imaging agents in normal and acutely ischemic brain. <h3>METHODS</h3> The magnetic susceptibility effects of intravenous injections of 0.10-0.50 mmol/kg of each contrast agent were quantified on T2-weighted spin-echo images of cat brain before and after unilateral occlusion of the middle cerebral artery by measuring signal intensity changes in the same regions-of-interest in parietal cortex. <h3>RESULTS</h3> In normal brain, DyDTPA-BMA produced a significantly greater loss of signal intensity than equimolar doses of GdDTPA-BMA. The magnitude of the signal intensity attenuation was dosage-dependent and proportional to the square of the magnetic moments of the two contrast agents. Restoration of baseline image signal intensity was observed within 30 min after each injection. However, injection of GdDTPA-BMA also produced a delayed, persistent hyperintensity on T2-weighted images, presumably due to its underlying T1-shortening effect. Following unilateral occlusion of the middle cerebral artery, unenhanced T2-weighted images failed to show evidence of cerebral injury for 1.5-3 hours. Administration of 0.10-1.0 mmol/kg DyDTPA-BMA shortened the time for detection of perfusion deficits (residual hyperintensity) in 22 of 36 (61%) treated cats, often to within 30 min after arterial occlusion. DyDTPA-BMA enhancement also improved lesion conspicuity in 26 of 36 (72%) cases, and disclosed very small infarcts that were not visible on T2-weighted precontrast images. Perfusion deficits in areas of partial ischemia were seen more clearly on DyDTPA-BMA-enhanced images than after equimolar injections of GdDTPA-BMA. <h3>CONCLUSIONS</h3> Magnetic susceptibility contrast-enhanced MR imaging enables detection of perfusion deficits associated with acute cerebral ischemia well in advance of conventional T2-weighted spin-echo MR imaging without contrast. DyDTPA-BMA appears to delineate regions of ischemic damage better than GdDTPA-BMA.
Creatine kinase MM isoenzyme subforms in myocardium, cardiac lymph and blood after coronary artery occlusion in dogs
Authors: D. R ABENDSCHEIN, R. L MORELLI, C J. CARLSON, B. EMILSON, E. RAPAPORT
Journal: Cardiovascular Research (1984)

A time-varying pattern of creatine kinase MM (CK-MM) isoenzyme subforms has been found in the blood of patients after acute myocardial infarction, but the site of enzyme modification has not been identified. Therefore, we studied the CK-MM subform patterns in myocardium, cardiac lymph and blood of dogs after coronary artery occlusion. In five conscious dogs, serial blood samples were taken for 72 h after occlusion of the left anterior descending coronary artery. Samples of non-infarcted and infarcted myocardium were taken after 72 h. In five other anaesthetised, open-chest dogs, cardiac lymph and blood samples were taken for 6 h after coronary artery occlusion. CK-MM subforms were quantitated by an isoelectric focusing method. Before coronary occlusion, 64% of the total CK activity in blood appeared as the anodal subform CK-MM 1 (pI 6.3); 20% and 9% as the cathodal subforms CK-MM 2 (pI 6.6) and CK-MM 3 (pI 6.9), respectively. However, after 2 h of coronary occlusion CK-MM 2 and CK-MM 3 were increased (38% and 17% of total activity respectively) compared with CK-MM 1. Between 4 h and 10 h, CK-MM 2 and CK-MM 3 decreased as CK-MM 1 increased restoring the control relative activities of subforms. In contrast to the subform changes in blood, CK-MM 3 was the predominant subform in both non-infarcted and infarcted myocardium after 72 h of coronary occlusion and in cardiac lymph during 6 h of coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Leptin-mediated neovascularization is a prerequisite for progression of nonalcoholic steatohepatitis in rats
Authors: Mitsuteru Kitade, Hitoshi Yoshiji, Hideyuki Kojima, Yasuhide Ikenaka, Ryuichi Noguchi, Kosuke Kaji, Junichi Yoshii, Koji Yanase, Tadashi Namisaki, Kiyoshi Asada, Masaharu Yamazaki, Tatsuhiro Tsujimoto, Takemi Akahane, Masahito Uemura, Hiroshi Fukui
Journal: Hepatology (2006)

Nonalcoholic steatohepatitis (NASH) may cause fibrosis, cirrhosis, and hepatocellular carcinoma (HCC); however, the exact mechanism of disease progression is not fully understood. Angiogenesis has been shown to play an important role in the progression of chronic liver disease. The aim of this study was to elucidate the role of angiogenesis in the development of liver fibrosis and hepatocarcinogenesis in NASH. Zucker rats, which naturally develop leptin receptor mutations, and their lean littermate rats were fed a choline-deficient, amino acid-defined diet. Both Zucker and littermate rats showed marked steatohepatitis and elevation of oxidative stress markers (e.g., thiobarbital acid reactive substances and 8-hydroxydeoxyguanosine). In sharp contrast, liver fibrosis, glutathione-S-transferase placental form (GST-P)-positive preneoplastic lesions, and HCC developed in littermate rats but not in Zucker rats. Hepatic neovascularization and the expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, only increased in littermate rats, almost in parallel with fibrogenesis and carcinogenesis. The CD31-immunopositive neovessels were mainly localized either along the fibrotic septa or in the GST-P-positive lesions. Our in vitro study revealed that leptin exerted a proangiogenic activity in the presence of VEGF. In conclusion, these results suggest that leptin-mediated neovascularization coordinated with VEGF plays an important role in the development of liver fibrosis and hepatocarcinogenesis in NASH.
Qualitative and Quantitative Analysis of Urinary Lipids in the Nephrotic Syndrome*
Authors: Saulo Klahr, K. Tripathy, Oscar Bolanos
Journal: Journal of Clinical Investigation (1967)

A qualitative and quantitative analysis of urinary lipids in the nephrotic syndrome is presented. The following lipids were identified in the urine of patients with the nephrotic syndrome: free cholesterol, cholesterol esters, triglycerides, free fatty acids, and phospholipids. Glass paper chromatography identified the cholesterol esters as palmitate, oleate, linoleate, and arachidonate, and identified the phospholipids as phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. Urinary lipid excretion was much greater in patients with the nephrotic syndrome than in patients with chronic renal disease and minimal proteinuria, or in patients with hyperlipidemia from other causes. Urinary lipid excretion varied widely among the 13 patients with the nephrotic syndrome studied, and no quantitative correlation with serum lipid levels was observed. However, qualitatively at least, the proportion of cholesterol esters excreted in the urine was similar to the proportion of these esters in plasma. A good correlation was found between lipid excretion and glomerular permeability. Furthermore, during steroid therapy urinary lipid excretion decreased concomitant with a decrease in proteinuria. All these observations support the idea that lipiduria in the nephrotic syndrome is related to protein loss and that most of the lipid in the urine enters the glomerular filtrate in the form of lipoproteins.
Effects of MF-tricyclic, a selective cyclooxygenase-2 inhibitor, on atherosclerosis progression and susceptibility to cytomegalovirus replication in apolipoprotein-E knockout mice
Authors: David Rott, Jianhui Zhu, Mary Susan Burnett, Y.i F.u Zhou, Alexandra Zalles-Ganley, Jibike Ogunmakinwa, Stephen E Epstein
Journal: Journal of the American College of Cardiology (2003)
Protection of mitochondrial function during ischemia by potassium cardioplegia: correlation with ischemic contracture.
Authors: J D Sink, G L Pellom, W D Currie, W R Chitwood, R C Hill, A S Wechsler
Journal: Circulation (1979)

The effect of potassium cardioplegia on mitochondrial function was evaluated in the ischemic isolated rat heart. Mitochondrial function as well as adenosine triphosphate (ATP) levels were determined at the initiation of ischemic contracture, at the completion of ischemic contracture, and 20 minutes following contracture completion. Group I received no cardioplegia prior to ischemia, while Group II received potassium cardioplegia prior to the onset of ischemia. The respiratory control index (RCI), which is the primary measure of the intactness of mitochondrial function, was calculated with both a NAD (nicotinamide adenine dinucleotide)-linked substrate and a FAD (flavin adenine dinucleotide)-linked substrate. Potassium cardioplegia significantly delayed ischemic contracture initiation and completion. Although the RCI and ATP levels decreased significantly at successive levels of contracture, there was no difference in the RCI or ATP content between Group I and Group II at contracture initiation or completion. Unlike previous investigations that have used a time-base to examine mitochondrial function and acute cardiac ischemic injury, we correlated mitochondrial function with the measurable physiologic event ischemic contracture. The data indicated that potassium cardioplegia preserved ATP content and mitochondrial function, and that contracture initiation and completion correlate well with specific ATP levels and mitochondrial respiratory control. The relationship between mitochondrial function and ATP content indicates that the beneficial effect of potassium cardioplegia on mitochondrial function may be secondary to the preservation of high-energy phosphate levels which provide energy for mitochondrial maintenance.
Multisystem Morbidity and Mortality in Offspring of Women With Type 1 Diabetes (the EPICOM Study): A Register-Based Prospective Cohort Study
Authors: Sine Knorr, Kirstine Stochholm, Zuzana Vlachová, Birgitte Bytoft, Tine D. Clausen, Rikke Beck Jensen, Svend Juul, Per Ovesen, Peter Damm, Henning Beck-Nielsen, Dorte M. Jensen, Claus Højbjerg Gravholt
Journal: Diabetes Care (2015)

OBJECTIVE This study examined the long-term consequences for offspring born to mothers with pregestational type 1 diabetes regarding mortality, hospital admissions, and medication. We also examined the association between HbA1c levels during pregnancy and mortality and incidence of hospital admissions. RESEARCH DESIGN AND METHODS We performed a prospective combined clinical and register-based cohort study comparing mortality, hospital admissions, and use of medication in offspring (n = 1,326) of women with pregestational type 1 diabetes (index children) with matched control subjects (n = 131,884). We also examined the association between HbA1c levels during pregnancy and mortality and the incidence of hospital admissions. Participants were monitored from birth to the age of 13–21 years. RESULTS Overall mortality was significantly increased for index children (hazard ratio 2.10, 95% CI 1.33–3.30, P = 0.001). The incidence of hospital admissions for index children was significantly increased (incidence rate ratio [IRR] 1.45, 95% CI 1.38–1.53, P &amp;lt; 0.001), and this was the case for all age groups until the age of 15 years. The incidence of hospital admissions among index children was positively associated with maternal HbA1c before pregnancy and in the first trimester. In addition, the overall use of medication was increased in index children (IRR 1.13, 95% CI 1.07–1.19, P &amp;lt; 0.001). CONCLUSIONS Type 1 diabetes during pregnancy has long-term implications on the health of offspring, with increased mortality, incidence of hospital admissions, and use of medication. Among mothers with type 1 diabetes, glycemic regulation is positively associated with incidence of hospital admissions in offspring.
MYOCARDIAL HIBERNATION IDENTIFIED BY HYPERBARIC OXYGEN TREATMENT AND ECHOCARDIOGRAPHY IN POSTINPARCTION PATIENTS
Authors: P C Swift, K V Woollard, H P Oxer, J P O??Shea, G K Lans, J H Turner
Journal: Clinical Nuclear Medicine (1992)

Swift, P C; Woollard, K V; Oxer, H F; O'Shea, J P; Lans, G K; Turner, J H Author Information
Rational decisions in managing sore throat: evaluation of a rapid test
Authors: P. Burke, J. Bain, A. Lowes, R. Athersuch
Journal: BMJ (1988)

Sixty nine general practitioners recorded what they had prescribed for a total of 1189 episodes of sore throat. Antibiotics were prescribed in 763 (64%) episodes and broad spectrum antibiotics in 161 (21%) of these. If there was dysphagia, hoarseness, cervical adenopathy, and inflamed or purulent tonsils a prescription was more likely to be written. An enzyme immunoassay rapid test was evaluated as a means of rationalizing prescribing. Among 23 general practitioners and 250 patients the sensitivity of the test was 63% and the specificity 91.7% compared with 74% and 58% for clinical assessment alone. Test results rarely caused previous prescribing decisions (34 [corrected] (13%) episodes) to be altered. We suggest that the time is not ripe for the use of the enzyme immunoassay rapid test on a wide scale in the routine assessment of sore throats.
Patient's response to the research
Authors: R. Saeed
Journal: BMJ (2003)

As I was reading through the study by Stokes and colleagues, I was astonished as to how familiar it all seemed, that there may be other people who have gone through the same ordeal and process as I have. I was rejected once by a general practitioner, and that could have affected my creditability in finding a GP.

My family and I have learnt that the services in the London suburbs are very limited and the people in the suburbs are very naive and not aware of their rights, unaware of how to handle situations, and kept in the dark by the authorities. It is not just …
Culture change matters more than technological change, US healthcare expert tells integrated care summit
Authors: D. Payne
Journal: BMJ (2012)

Integrating health and social care more closely should be seen as a sociological rather than technological challenge, says the US doctor who deployed electronic health records for hospital and clinics serving US veterans.

When Kenneth Kizer took over as head of the Department for Veterans Affairs in 1994, the staff was demoralised by the federal bureaucracy’s risk averse and punitive culture. Patients faced long waiting times, and the service was highly hospital-centric. First established in 1946 to provide treatment for veterans with combat related injuries, Veterans Affairs is now the largest provider of healthcare services in the United States, with outposts in Guam, Samoa, and …
The effect of an isovolumic left ventricle on the coronary vascular competence during reflow after global ischemia in the rat heart.
Authors: S M Humphrey, R W Thomson, J B Gavin
Journal: Circulation Research (1981)

During global ischemia in isolated rat hearts, the development of contracture, due to irreversible myofilament sliding, causes reduction of left ventricle luminal volume. Also, a considerable area of the myocardium cannot be reperfused after 1 hour's global ischemia. The purpose of this study was to reduce myofilament sliding by placing a fluid-filled isovolumic balloon in the left ventricular cavity of isolated rat hearts and assess the extent of reflow, after 60 minutes' ischemia, by perfusion of a 1% fluorescein tracer solution. Light and electron microscopy was used to determine the state of the vasculature and myofibrillar apparatus. In hearts without the left ventricular balloon (control) the ischemia produced a no-reflow zone comprising 45% of the myocardial wall. In contrast, if an isovolumic balloon was in place during the ischemic period, only 6% of the wall was involved. The volume of the capillary bed in the subendocardium of the control hearts was about 60% of that in th isovolumic hearts. In the isovolumic ("isometric") mode, ischemic contracture was associated with more severe myocardial cell injury than in the corresponding control ("isotonic") mode. Our results support the concept that intramyocardial pressure generated by ischemic contracture plays a major role in the production of the no-reflow phenomenon in globally ischemic rat hearts, and indicate that it is the series elastic component of cardiac muscle which imparts the stiffness necessary to prevent reopening of coronary vessels after a severe ischemic insult.
The Administration of Ether, and its Superiority to Chloroform as an Anaesthetic Agent
Authors: J. Morgan
Journal: BMJ (1872)

In deducing the effects of alcohol from this comparison, it is neces- sary to allow for the somewhat lessened exposure to weather, and also to accidental violence, involved in the alcoholic pursuits-exemptions which, so far as they go, would diminish the liability to tubal nephritis and to lardaceous change.This may help to explain the comparative rarity of these disorders with the alcoholic class.The increase in fibroid and chronic tubal changes must be referred to the liquor alone; but this increase is not great.Taking all the facts together, I do not see how it can be doubted that the effects of alcohol in causing renal disease is less than used to be asserted: that to paraphrase Dr. Roberts, if he will allow me to do so, this agent does not rank higher, but lower, than other circumstances- to wit, external temperature and the absorption of lead-as a determin- ing cause of Bright's disease.Although we can now and then trace the existence or aggravation of renal symptoms to intemperance, we do so with far less frequency than with disorders which have other sites.Pathological and clinical evidence combine to show that the evil influ- ence tells more upon the nervous system, the liver, the blood-vessels, and probably in the production of tuberculosis, than upon the kidneys.The facts adduced are consistent with those formerly advanced, and with the quoted conclusions which have been the object of attack.
Frontiers of Gastrointestinal Research, vol 1: Immune Disorders
Authors: Howard M. Spiro
Journal: JAMA (1975)

<i>Frontiers of Gastrointestinal Research</i>is a new series of paperbound books "intended to provide reports of recent advances in gastroenterology to the clinician and research worker." The first volume,<i>Immune Disorders</i>, has chapters on gastrointestinal allergy, gastritis, celiac disease, inflammatory bowel disease, and chronic active hepatitis, all by workers well known in their fields. The references are up-to-date, some from 1973 and 1974, but generally the reports are simply a rewrite of information available elsewhere. I found nothing in the book to justify paying $41 for a paperbound volume of 187 pages. The book provides useful reading and good reference material but is much too expensive. Indeed, there is no information that could not have appeared with equal propriety and at much less expense in a journal, possibly even the one published by S. Karger. The price will keep the book out of the hands of the clinical and research
Proper antiviral therapy for hepatitis B virus-associated acute-on-chronic liver failure
Authors: Tao Liu, Chunmei Zhang, Yingjie Wang
Journal: Hepatology (2011)

Convincing evidence that antiviral therapy contributes to reduce short-term mortality of patients with hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) is still unavailable.1, 2 I read with great interest the article by Garg et al.,3 who demonstrated that tenofovir can reduce the mortality of patients with severe spontaneous reactivation of chronic hepatitis B presenting as ACLF. Their optimistic results give us some evidence about antiviral therapy in HBV-associated ACLF. However, a recent prospective cohort study by Wong et al.4 demonstrated that entecavir treatment, as compared to lamivudine treatment, is associated with increased short-term mortality of patients with severe acute exacerbation of chronic hepatitis B. Both tenofovir and entecavir are now the most effective antiviral agents for chronic hepatitis B. But why did they have converse effects upon the short-term mortality of HBV-associated ACLF? Here, we would like to offer some possible reasons for this interesting question. First, Garg et al. identified patients with HBV-associated ACLF by a high HBV DNA level (>105 copies/mL).3 The criterion on which their previous study is based may be useful, but it is still immature with only 14 patients enrolled in the tenofovir treatment group. There are obviously distinct prognoses between acute hepatitis B–related liver failure and HBV-associated ACLF. Therefore, enrollment of any patients with acute HBV-related liver failure may interfere with the results. Besides, genotype D was the predominant HBV genotype in the Indian study subjects (85.2%), but genotype B or C is the main HBV genotype in China. Also, it is still unknown whether HBV genotype may affect the results of antiviral treatment in ACLF. In addition, Wong et al. speculated that the problem of lactic acidosis or an exaggerated immune response due to rapid virological suppression may lead to and exacerbate liver injury among patients with severe acute exacerbation of chronic hepatitis B.4 However, the latter explanation is contradictory to the opinion of Garg et al., who proposed that rapid reduction in HBV DNA levels independently predicted a good short-term survival rate. Thus, larger prospective and multicentric studies are encouraged to further evaluate the affect of tenofovir and entecavir on short-term mortality of patients with HBV-associated ACLF. Tao Liu M.D.* , Chunmei Zhang M.D.*, Yingjie Wang M.D. , * Department of Internal Medicine III, The Northern Region of No. 401 Hospital, Qingdao, Shandong, China, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.
Risk of Cancer in Patients With Inflammatory Bowel Diseases: A Nationwide Population-based Cohort Study With 30 Years of Follow-up Evaluation
Authors: Michael D. Kappelman, Dora K. Farkas, Millie D. Long, Rune Erichsen, Robert S. Sandler, Henrik T. Sørensen, John A. Baron
Journal: Clinical Gastroenterology and Hepatology (2013)