tbuckley/cabot-search huggingface dataset:
Expression of p21cip1, p27kip1, and p16INk4a Cyclin-Dependent Kinase Inhibitors in Papillary Thyroid Carcinoma: Correlation with Clinicopathological Factors
Authors: Carles Zafon, Gabriel Obiols, Josep Castellví, Santiago Ramon y Cajal, Juan Antonio Baena, Jordi Mesa
Journal: Endocrine Pathology (2008)
Myoclonus associated with high doses of morphine
Authors: H J McQuay, D J Gorman, G W Hanks
Journal: BMJ (1989)

so; however, the evidence supporting such a practice is no better than that supporting the other treatments reviewed.The two studies cited are both retrospective surveys without randomised controls."There really is insufficient evidence on the dose-response relation of inhaled steroids in terms of either wanted or unwanted side effects to allow a firm statement in the context of patients taking oral steroids.We do not know whether 5 mg of oral prednisolone is more than 2 mg of inhaled beclomethasone in terms of osteoporosis or other serious systemic side effects.It is worth remembering that beclomethasone is many times more potent dose for dose than prednisolone and that most of the inhaled drug is swallowed.We agree with Dr Wilkinson that treating psychological factors may have a role in managing this type of patient.However, in a disease such as asthma, which is associated with such a strong placebo effect, only rigidly controlled prospective studies can prove the efficacy of a particular approach to treatment.Sadly, these trials are lacking.
Home versus hospital deliveries: follow up study of matched pairs for procedures and outcome
Authors: U. Ackermann-Liebrich, T. Voegeli, K. Gunter-Witt, I. Kunz, M. Zullig, C. Schindler, M. Maurer, Z. S. Team
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To assess procedures and outcomes in deliveries planned at home versus those planned in hospital among women choosing the place of delivery. <b>Design</b>: Follow up study of matched pairs. <b>Setting</b>: Antenatal clinics and reference hospitals in Zurich between 1989 and 1992. <b>Subjects</b>: 489 women opting for home delivery and 385 opting for hospital delivery; the women comprised all those attending members of the study team for antenatal care and those attending the reference hospital for antenatal care who could be matched with the women planning home confinement. <b>Main outcome measures</b>: Need for medication and incidence of interventions during delivery (caesarean section, forceps, vacuum extraction, episiotomy), duration of labour, occurrence of severe perineal lesions, maternal blood loss, and perinatal morbidity and death. <b>Results</b>: All women were followed up from their first antenatal visit till three months after delivery. Referrals during pregnancy (n = 37) and labour (70), changes of mind (15 home to hospital, eight hospital to home), and 17 miscarriages resulted in 369 births occurring at home and 486 in hospital. During delivery the home birth group needed significantly less medication and fewer interventions whereas no differences were found in durations of labour, occurrence of severe perineal lesions, and maternal blood loss. Perinatal death was recorded in one planned hospital delivery and one planned home delivery (overall perinatal mortality 2.3/1000). There was no difference between home and hospital delivered babies in birth weight, gestational age, or clinical condition. Apgar scores were slightly higher and umbilical cord pH lower in home births, but these differences may have been due to differences in clamping and the time of transportation. <b>Conclusion</b>: Healthy low risk women who wish to deliver at home have no increased risk either to themselves or to their babies. <h3>Key messages</h3> Interventions (induction, caesarean section, medication, forceps, or vacuum extraction) may be considerably less frequent in women who originally opt for home delivery There are no obvious disadvantages of home delivery for mother or child when the mother opts for home delivery More studies are needed to look into the small risks of death, serious bleeding, and complications of interventions, which could not be evaluated in this study owing to limited power
Note on Cuca
Authors: W. W. Campbell
Journal: BMJ (1884)

tion of the forimier.It is more than prol)able, however, wvhen oneo considers the complexity of tlhe cord, that restoration of tl mlsicle- lharmony may follow in tlhe couirse of tinmc, an,d eveittually the knieejork be recovered, non-uniiioni of the iferve still existing.It is not my intention at present to ofrer this as ani expl nation of th loss anti subscquent returtn of kncc-jerk in certain ca.('5SAci tabes, the questioI l)eing one of greater complexity.Muse,lc-tone is the great factor in. the productioa of t,lonll-pllenomnca.Normally, the mnsvles of the whole hunalln frame2 ex;ist in a cortain state of tension, whicl, to sonile cxtePnt.at 1eaSt, is A14 o-pedenlt upoJI thO miotor nerves and tlheir' centrail connection.The sodden and moro or lcss complete abolition of tone is suflicient to stay the tcin(lol1- phonomnenoin.If tho spinal cord be eompletely divided, there is i1mmediate inter- forence with this toninir influence, anid absence of rellex.The absence of reflex, ulnder such circumnstances, lhas been imipntel to shock.-,Elasticity, or, better still, tonicity, is ani inhlereint quality of muscle itself, restrained by nerve-force.Tlhe suddlen, withdrawal of this ruling inifluienco brings about loss of tone, mlore or less completo for the time being.This property of muilscle, unider slightly altered circumstainces, may be readily exhaustedl, but not for aniy length of time, as recoverly is rapid.The exhaustion iiiay be one eitlher of musele or of nerve.Ervidence, oni the whlole, goes to show that knee-jerk is not reflex, but duo to direct stiilulatioin of the muscle by way of tlhe tenidoninevertlhless, and( this is the poinit of interest, normal integrity of the spinal cord and its coninectionis with muscles is essenitial for the pro- duction of the phenioruenloia.TREATAMENT OF ITLEMORRHAGE AFTER REICTAL OPERATIONS.1Y SAPMUEL BENTON, L.R OP., P R
Patient Characteristics Compete with Dose as Predictors of Acute Treatment Toxicity in Early Phase Clinical Trials
Authors: André Rogatko, James S. Babb, Hao Wang, Michael J. Slifker, Gary R. Hudes
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study was to identify patient characteristics that may be risk factors or markers of susceptibility to adverse treatment effects in cancer Phase I and II clinical trials. Patients and Methods: A total of 459 patients enrolled in 23 therapeutic Phase I and II studies at the Fox Chase Cancer Center were included in the analysis. Patient-specific characteristics, medical and treatment history, doses of experimental agents, and graded toxicities were extracted from case report forms. We developed a novel summary measure, the toxicity index (TI), to better discriminate patients on the basis of their overall toxicity experiences. Mixed model ANOVA was used to model TI on the basis of data from all trials using a specific agent. Generalized estimating equations in the context of binary logistic regression were used to model dose-limiting toxicity. Results: Seventeen pretreatment factors, including performance status, alkaline phosphatase, total bilirubin, serum creatinine, and tobacco use, emerged as significant predictors of toxicity as defined by dose-limiting toxicity or TI. Unexpectedly, dose was not always a predictor of toxicity. Even for values within the normal range, the TI identified serum bilirubin and alkaline phosphatase as predictors of toxicity after treatment with docetaxel and alkaline phosphatase as a predictor for toxicity after treatment with irinotecan. Conclusions: Independent of dose, certain pretreatment characteristics, including measures of organ function that are in the normal range, were found to be predictors of treatment toxicity. Because of its sensitivity to differences in overall toxicity, the TI should prove to be a useful tool for identifying predictors of chemotherapy-related toxicity.
Phosphorylation of LKB1 at Serine 428 by Protein Kinase C-ζ Is Required for Metformin-Enhanced Activation of the AMP-Activated Protein Kinase in Endothelial Cells
Authors: Zhonglin Xie, Yunzhou Dong, Roland Scholz, Dietbert Neumann, Ming-Hui Zou
Journal: Circulation (2008)

Background— Metformin, one of most commonly used antidiabetes drugs, is reported to exert its therapeutic effects by activating AMP-activated protein kinase (AMPK); however, the mechanism by which metformin activates AMPK is poorly defined. The objective of the present study was to determine how metformin activates AMPK in endothelial cells. Methods and Results— Exposure of human umbilical vein endothelial cells or bovine aortic endothelial cells to metformin significantly increased AMPK activity and the phosphorylation of both AMPK at Thr172 and LKB1 at Ser428, an AMPK kinase, which was paralleled by increased activation of protein kinase C (PKC)-ζ, as evidenced by increased activity, phosphorylation (Thr410/403), and nuclear translocation of PKC-ζ. Consistently, either pharmacological or genetic inhibition of PKC-ζ ablated metformin-enhanced phosphorylation of both AMPK-Thr172 and LKB1-Ser428, suggesting that PKC-ζ might act as an upstream kinase for LKB1. Furthermore, adenoviral overexpression of LKB1 kinase-dead mutants abolished but LKB1 wild-type overexpression enhanced the effects of metformin on AMPK in bovine aortic endothelial cells. In addition, metformin increased the phosphorylation and nuclear export of LKB1 into the cytosols as well as the association of AMPK with LKB1 in bovine aortic endothelial cells. Similarly, overexpression of LKB1 wild-type but not LKB1 S428A mutants (serine replaced by alanine) restored the effects of metformin on AMPK in LKB1-deficient HeLa-S3 cells, suggesting that Ser428 phosphorylation of LKB1 is required for metformin-enhanced AMPK activation. Moreover, LKB1 S428A, like kinase-dead LKB1 D194A, abolished metformin-enhanced LKB1 translocation as well as the association of LKB1 with AMPK in HeLa-S3 cells. Finally, inhibition of PKC-ζ abolished metformin-enhanced coimmunoprecipitation of LKB1 with both AMPKα1 and AMPKα2. Conclusions— We conclude that PKC-ζ phosphorylates LKB1 at Ser428, resulting in LKB1 nuclear export and hence AMPK activation.
NEUROTIC ATROPHY OF BONE.
Authors: ARTHUR E. PRICE
Journal: JAMA (1897)

The study of neurotic atrophy of bone as a pathologic research, may be outlined in general in the same manner as ordinary atrophy of these structures; not necessarily depending on the causes of the latter, but resembling each other greatly in the characteristic state of degeneration. The change is a structural one in which certain portions of cells that properly should combine with oxygen are thus rendered soluble and remain; a fatty degeneration ensuing. Thomas Curling of London, was the first to differentiate between concentric and eccentric atrophy of bone, by experiments with electricity, on degenerated nerves, and by cutting off the blood supply to bones. He demonstrated that the nutrition and also the vital powers of bone, being suspended, a process of resorption of the harder or more component parts occurred, and the compact structure changed into one closely resembling cancellous tissue. The gradual softening and loss of weight
Hemodynamic effects of levosimendan in addition to dobutamine infusion in patients with advanced heart failure intractable to dobutamine infusion alone
Authors: Panagiotis Papazoglou, Maria Anastasiou-Nana, Eleftheria Tsagalou, John Terrovitis, Elias Tsolakis, Argirios Dalianis, George Alexopoulos, John Kanakakis, Konstantinos Christodoulou, John N. Nanas
Journal: Journal of the American College of Cardiology (2003)
Suggestions for Effectiveness in Diagnosis
Authors: MILES J. BREUER
Journal: Annals of Internal Medicine (1929)

Article1 July 1929Suggestions for Effectiveness in DiagnosisMILES J. BREUER, M.D., F.A.C.P.MILES J. BREUER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-1-57 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe science of diagnosis is by this time fairly well advanced. The physical and laboratory findings of known pathological conditions have been thoroughly worked out, are well described in numerous and excellent texts, and are efficiently taught in the schools. Methods of examining, of performing tests, of eliciting signs, have been developed to a fairly high degree of perfection. Students are systematically drilled in them, and practitioners have access to an infinite store of literature dealing with them.Yet, with the vast accumulation of diagnostic material freely available, and with all the students systematically put through the drill in it... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: MILES J. BREUER, M.D., F.A.C.P.Affiliations: Lincoln, Nebraska PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTuberculin TherapyMILES J. BREUER, M.D., F.A.C.P. 1 July 1929Volume 3, Issue 1Page: 57-62KeywordsResearch laboratories ePublished: 1 December 2008 Issue Published: 1 July 1929 PDF downloadLoading ...
Audit in Person: Review: Audit kit for childhood asthma
Authors: P J Rees
Journal: BMJ (1990)

Dr Tim Usherwood has produced an asthma audit kit for general practitioners which is designed to audit the care of children aged 5 to 14 years, although there is no reason why it should not be adapted to other age groups.The programme has two aims; firstly, to provide a complete kit to save general practitioners designing their own and, secondly, to generate a large database to allow Dr Usherwood to analyse the care of childhood asthma in general practice.The audit has six stages, although only the first three-setting up an asthma register, audit of current management, and a parental questionnaire concerning control-are provided in the kit.The subsequent stages are: feedback of data from other practices, planning future developments, and a second audit two years later.Management of asthma is an excellent target for audit.The programme is likely to produce some useful material on differences among practices and the general standard of control of asthma in general practice.I am less sure that it is the right tool for all individual practices.However, just as participation in a trial of asthma improves control, even for placebo groups, the attention to managing asthma will probably lead to improvements just by concentration of effort on one aspect.
Code of Medical Ethics: Current Opinions With Annotations
Authors: Arthur L. Caplan
Journal: JAMA (1995)

It is time to give some credit where credit has for some time been wanting. For many, many years the last place anyone with a serious interest in the ethics of health care would be tempted to look for weighty moral analysis was the Code of Medical Ethics of the American Medical Association. Nothing in the Code made it into standard anthologies of bioethics. Almost no scholarly journals, including this one, would even bother to review the document. Up until 1955 the AMA Code had far more to do with matters of etiquette and professional comportment than with substantive matters of morality. It was not until 1980 that the Judicial Council of the AMA, today the Council on Ethical and Judicial Affairs, issued a revision of the AMA Principles of Medical Ethics that went beyond the norms that ought to be followed by physicians in private practice into the much
Vagal Stimulation and VF
Authors: WARNER MEESMANN, KLAUS STEPHAN
Journal: Circulation (1974)

EDITORdle scallop and anterior leaflet prolapse produce a denser central bulge compared to the less dense commissural bulges.'0Of perhaps greater significance in the distinction between anterior and posterior leaflet prolapse is the use of the left anterior oblique left ventricular cineangiogram in these patients.In this view, the anterior leaflet is well visualized in diastole hanging down from the aortic root to which it is attached.In systole, if it should prolapse, it moves into the left atrium, the fulcrum of its movement being at the aortic root.'0In the case of the patient reported in figure 2 of our paper," none of these criteria for anterior leaflet prolapse were present.Therefore we believe that the anterosuperior bulge in figure 2 was due to anterolateral commissural scallop prolapse8 and not due to anterior leaflet prolapse as has been suggested by Dr. Jeresaty.Pathological findings of the valve in this case revealed minor thickening without myx- omatous degeneration in the anterior leaflet and gross myxomatous change with a thickened, hooded appearance to the scallops of the posterior leaflet, in- eluding the anterolateral commissural scallop.8
A 69-Year-Old Female with Tiredness and a Persistent Tan
Authors: Petros Perros
Journal: PLoS Medicine (2005)

69-year-old female presented with palpitations and a history of tiredness and shortness of breath for several weeks. She had a previous history of Raynaud syndrome. She was an ex-smoker. She commented that she had not lost her tan since the previous summer. Her only medication was nifedipine for her Raynaud syndrome.On examination, she was slim and tanned. Pulse rate was 86 beats per minute and regular. Her blood pressure (BP) was 105/74 mm Hg. Her chest was hyperinﬂ ated. The rest of her examination was recorded as normal. A chest X ray showed no evidence of cardiac failure. Electrocardiogram monitoring showed episodes of atrial ﬁ brillation. Her routine biochemistry was as follows: serum sodium, 132 mmol/l (normal range, 135–145 mmol/l); potassium, 5.1 mmol/l (3.4–5 mmmol/l); urea, 8.6 mmol/l (2.5–6.4 mmol/l); and creatinine, 110 mmol/l (65–120 µmol/l).She was commenced on digoxin and warfarin. Her breathlessness gradually improved, and she remained in sinus rhythm.
Role of Endothelin-1/Endothelin-A receptor-mediated signaling pathway in the aortic arch patterning in mice.
Authors: H Yanagisawa, R E Hammer, J A Richardson, S C Williams, D E Clouthier, M Yanagisawa
Journal: Journal of Clinical Investigation (1998)

The intercellular signaling mediated by endothelins and their G protein-coupled receptors has recently been shown to be essential for the normal embryonic development of subsets of neural crest cell derivatives. Endothelin-1 (ET-1) is proteolytically generated from its inactive precursor by endothelin-converting enzyme-1 (ECE-1) and acts on the endothelin-A (ETA) receptor. Genetic disruption of this ET-1/ECE-1/ETA pathway results in defects in branchial arch- derived craniofacial tissues, as well as defects in cardiac outflow and great vessel structures, which are derived from cephalic (cardiac) neural crest. In this study, in situ hybridization of ETA-/- and ECE-1(-)/- embryos with a cardiac neural crest marker, cellular retinoic acid-binding protein-1, shows that the migration of neural crest cells from the neural tube to cardiac outflow tract is not affected in these embryos. Immunostaining of an endothelial marker, platelet endothelial cell adhesion molecule CD-31, shows that the initial formation of the branchial arch arteries is not disturbed in ETA-/- or ECE-1(-)/- embryos. To visualize the subsequent patterning of arch vessels in detail, we generated ETA-/- or ECE-1(-)/- embryos that expressed an SM22alpha-lacZ marker transgene in arterial smooth muscle cells. Wholemount X-gal staining of these mutant embryos reveals that the abnormal regression and persistence of specific arch arteries results in disturbance of asymmetrical remodeling of the arch arteries. These defects include abnormal regression of arch arteries 4 and 6, enlargement of arch artery 3, and abnormal persistence of the bilateral ductus caroticus and right dorsal aorta. These abnormalities eventually lead to various types of great vessel malformations highly similar to those seen in neural crest-ablated chick embryos and human congenital cardiac defects. This study demonstrates that ET-1/ETA-mediated signaling plays an essential role in a complex process of aortic arch patterning by affecting the postmigratory cardiac neural crest cell development.
NADPH-STIMULATED SUPEROXIDE AS A SENSITIVE MARKER OF CELLULAR OXIDATIVE STRESS: ITS VALUE AS A MARKER OF VASCULAR FUNCTION IN HUMAN ATHEROSCLEROSIS
Authors: Alexios S. Antonopoulos, Charalambos Antoniades, Dimitris Tousoulis, Michael Demosthenous, Antigoni Miliou, Constantinos Bakogiannis, Constantinos Psarros, Nikolaos Koumallos, Charalambos Vlachopoulos, Christodoulos Stefanadis
Journal: Journal of the American College of Cardiology (2012)
Complement defect linked to early strokes
Authors: William A. Check
Journal: JAMA (1982)

A deficiency of the second component of complement, called C2, may somehow be related to the occurrence of strokes in young people. Speaking at the Joint International Conference on Stroke and Cerebral Circulation in New Orleans, neurologist Denis Simard, MD, described 11 patients with such deficiency. They were among 30 stroke victims under the age of 42 years admitted to the Hôpital l'Enfant-Jesus in Quebec city during the last two years. The mean age of the complement-deficient stroke victims was 27 years. (The mean age for stroke victims in the population at large is between 60 and 70 years.) The 11 patients were identified during an extensive workup. In contrast, ten randomly selected older stroke patients (aged between 48 and 70 years) had normal C2 levels, said Simard. He added that the C2-deficient patients experienced fluctuations in their C2 levels during follow-up, but that the values never went back to
Abstract 3406: Impact of TJP-1 and TWIST expression on post-operative prognosis in hepatocellular carcinoma
Authors: Tomoyuki Nagai, Tokuzo Arao, Kazuko Matsumoto, Kazuko Sakai, Kanae Kudo, Hiroyasu Kaneda, Daisuke Tamura, Keiichi Aomatsu, Hideharu Kimura, Yoshihiko Fujita, Satoru Hagiwara, Toshiharu Sakurai, Kazuomi Ueshima, Seiji Haji, Masatoshi Kudo, Kazuto Nishio
Journal: Cancer Research (2012)

Abstract Epithelial-Mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. However, whether the overexpression of EMT-related genes mediates the malignant phenotype in HCC remains largely unclear. In this study, we examined the relationship between mRNA expression levels of EMT-related genesand 12 clinical characteristics including recurrence-free survival and overall survival in HCC patients who had undergone curative hepatic resection. The mRNA expression levels of 15 genes (CDH1, CDH2, Snail, Slug, ZEB1, ZEB2, TWIST, Vimentin, Fibronectin, DDR2, S100A4, TJP-1/ZO-1, FOXC2, SIX1, GSC) was determined by quantitative real-time PCR in tissues from 72 HCC tumors. Twist expression was significantly upregulated in recurrence group (p=0.02). The upregulation of Twist and the downregulation of TJP1 were significantly related with poor prognosis in univariate and multivariate analysis. In conclusion, Twist and TJP1 may be predictive biomarkers in patients with HCC after hepatectomy. Our findings provide a novel insight into TJP1 and HCC, warranting further investigations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3406. doi:1538-7445.AM2012-3406