tbuckley/cabot-search huggingface dataset:
Randomized phase III study of trastuzumab monotherapy followed by docetaxel and trastuzumab versus the combination of trastuzumab and docetaxel as first-line treatment in patients with HER2 positive metastatic breast cancer.
Authors: K Najagami, K Inoue, M Mizutani, Y Hozumi, Y Fujiwara, N Masuda, F Tsukamoto, M Saito, Y Ohashi, M Sano, S Noguchi
Journal: Cancer Research (2009)

Abstract Abstract #3132 Introduction: Treatment with trastuzumab (H) is a standard therapy for the patients with HER2 positive metastatic breast cancer (MBC) and both the combination with H and chemotherapy (CT) and H alone are very popular. However, it is unknown which is better; sequential H alone followed by combination of CT and H at disease progression or the combination with H and CT as first-line therapy. Therefore, we conducted phase III randomized trial compared them in HER2 positive MBC.&amp;#x2028; Methods: Eligible patients were HER2 positive MBC patients (pts) with measurable tumour based on RECIST, ECOG Performance status 0 or 1 and left ventricular ejection fraction (LVEF) &amp;gt;50%. Patients with prior CT for MBC, adjuvant H, and Docetaxel (DTX) were excluded. They were randomly assigned to sequential weekly H 2 mg/kg (loading 4 mg/kg) alone followed by combination of DTX (60 mg/m2, q3wks) and H at disease progression (arm A) or concurrent combination of H and DTX (arm B). Primary endpoints were time to progression (TTP) of H alone (arm A) and combination of H and DTX (arm B) and overall survival (OS). Secondary endpoints were overall response rate (ORR), TTP and safety in arm A and B.&amp;#x2028; Results:Of the 108 pts registered, 105 pts were eligible. Baseline characteristics of all pts in two groups were well-balanced. Median age was 57/55 years, prior adjuvant CT 38/45% and single metastatic site 30/31% in arm A and B, respectively. Median TTP in arm A was 137 days compared to 445 days in arm B (hazard ratio=4.15; P&amp;lt;0.0001). ORRs were 15% and 71% in arm A and B, respectively. Median OS has not been reached yet, however, the number of deaths were 11 pts in arm A and 4 pts in arm B (hazard ratio=3.36; P=0.028). Adverse event incidence of grade 3 or 4 was 51/85% in each arm. An Efficacy and Safety Evaluation Committee recommended stopping this trial based on the results of TTP and OS.&amp;#x2028; Discussion: These results suggested that the combination of H and CT is superior to sequential H alone followed by DTX and H as first-line therapy in HER2 positive MBC pts despite the number of pts did not reach to the planned sample size. We will continue further investigation based on extended follow-up period. The updated data will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3132.
A New Approach to Evaluation of Left Heart Lesion.
Authors: William L. Page
Journal: Annals of Internal Medicine (1964)

s1 October 1964A New Approach to Evaluation of Left Heart Lesion.William L. Page, M.D., Daniel Allensworth, M.D., James J. Leonard, M.D. (Associate), Donald Leon, M.D.William L. Page, M.D.Search for more papers by this author, Daniel Allensworth, M.D.Search for more papers by this author, James J. Leonard, M.D. (Associate)Search for more papers by this author, Donald Leon, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-800_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIntracavitary phonocardiography has proved valuable in the diagnosis of lesions of the right heart. By the retrograde approach, phonocardiographic evaluation of aortic outflow lesions has been possible. At present, lesions of the mitral valve and left atrium have not been accessible to this type of evaluation. By simple modifications of the standard transseptal catheter technique, we have obtained intracardiac phonocardiograms from both the left atrium and left ventricle with simultaneous pressure recordings.The technique was initially used to study ten patients with mitral stenosis. The diastolic murmur was present in the left ventricle below the mitral valve. Its duration could... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHLate systolic murmurs, clicks, and whoops arising from the mitral valveMild mitral regurgitation 1 October 1964Volume 61, Issue 4Page: 800-800KeywordsCathetersHeartLeft atriumLeft ventricleLesionsMitral stenosis Issue Published: 1 October 1964 PDF DownloadLoading ...
LATENT LIFE OF ARTERIES
Authors: Alexis Carrel
Journal: The Journal of Experimental Medicine (1910)

When a segment of artery, killed by heat, formalin or glycerin is transplanted, it undergoes a rapid degeneration. Its muscle fibers disappear while the tissue of the host reacts by building a new wall of connective tissue. When the transplanted vessel has been preserved in a condition of latent life, no degeneration of the wall occurs, or the wall undergoes only partial degeneration. The muscle fibers can keep their normal appearance, even for a long time after the operation. It is, therefore, demonstrated that arteries can be preserved outside of the body in a condition of unmanifested actual life. The best method of preservation consists of placing the vessels, immersed in vaselin, in an ice box, the temperature of which is slightly above the freezing point. From a surgical standpoint, the transplantation of preserved vessels can be used with some safety. When the arteries were kept in defibrinated blood or vaselin and in cold storage, the proportion of positive results was 75 and 80 per cent., and this can probably be increased.
Comparison of two in-laboratory titration methods to determine effective pressure levels in patients with obstructive sleep apnoea
Authors: M P Bureau
Journal: Thorax (2000)

<h3>BACKGROUND</h3> Treatment of the sleep apnoea/hypopnoea syndrome with nasal continuous positive airway pressure (CPAP) conventionally requires a titration procedure in a sleep laboratory. The upper airway has a hysteresis phenomenon which accounts for a decrease in the effective positive pressure level once an initial effective pressure setting has been reached. The aim of this study was to quantify the difference in the initial and final effective pressure settings when the titration sleep study takes into account these possible changes in the effective pressure level. <h3>METHODS</h3> Eighty five patients completed the study. During a titration sleep study the pressure was increased by 1 cm H<sub>2</sub>O in a stepwise fashion until obstructive respiratory events disappeared (effective pressure 1, Peff<sub>1</sub>). The pressure level was then decreased by increments of 1 cm H<sub>2</sub>O until breathing abnormalities reappeared. At this time pressure was re-increased by increments of 1 cm H<sub>2</sub>O to normalise breathing (Peff<sub>2</sub>). <h3>RESULTS</h3> The mean (SD) value of Peff<sub>1</sub> was 9.5 (2.6) cm H<sub>2</sub>O. The pressure was then reduced during 0.5 (0.6) hours to reach the minimal pressure (7.0 (2.0) cm H<sub>2</sub>O). The pressure obtained after a downward titration had to be re-increased in 79 patients, the Peff<sub>2</sub> level being significantly lower than Peff<sub>1</sub> (8.9 (2.8) cm H<sub>2</sub>O, p = 0.0002), mean difference 0.6 (1.5) cm H<sub>2</sub>O (95% confidence interval 0.29 to 0.93). <h3>CONCLUSION</h3> Attempts to decrease the positive pressure level during conventional determination of the effective pressure level allow a significant decrease in the pressure setting. This should be taken into account in each patient who requires an in-laboratory manual CPAP titration procedure.
Jejunal intraepithelial lymphocytes in coeliac disease: are they increased or decreased?
Authors: G R Corazza, M Frazzoni, G Gasbarrini
Journal: Gut (1984)

We have quantified intraepithelial lymphocytes in the same biopsy series (21 healthy controls, 14 untreated coeliacs, 15 treated coeliacs, five non-coeliac patients with an abnormal jejunal mucosa) both as counts/100 epithelial cells and using as reference value a fixed area of muscularis mucosae. As expected, the number of intraepithelial lymphocytes/100 epithelial cells was significantly higher in untreated and treated coeliacs than in healthy controls, as well as in untreated when compared with treated coeliac patients. Otherwise, the number of intraepithelial lymphocytes lying in the area of mucosal surface overlying a fixed area of muscularis mucosae was significantly lower in treated and untreated coeliacs, than in healthy controls, as well as in untreated when compared with treated coeliacs. A highly significant inverse correlation was found between the number of intraepithelial lymphocytes/100 epithelial cells and the mucosal surface area measured as surface to volume ratio. When the number of intraepithelial lymphocytes/100 epithelial cells was corrected for differences in surface to volume ratio, the results were very similar to those obtained by a muscularis mucosae related count. In five coeliacs both intraepithelial lymphocyte and enterocyte muscularis mucosae related counts rose after a period of gluten free diet but the mean per cent increase of enterocytes was significantly higher than that of lymphocytes. Our results are compatible with a decrease in the total number of intraepithelial lymphocytes in the entire small bowel in coeliac disease. In untreated coeliac mucosae, however, a derangement in the usual proportions of intraepithelial lymphocytes and enterocytes is evident and may be important in the pathogenesis of coeliac disease.
Through Darkest Adolescence, With Tongue in Cheek and Pen in Checkbook
Authors: Lester S. King
Journal: JAMA (1965)

Adolescence is a disease, ordinarily self-limited and fortunately not contagious. Richard Armour offers a delightful clinical study of this disease. Witty and droll, the presentation exerts upon the reader a broad range of effects, from a gentle smile to a sage nod of the head, to a hearty belly laugh. The humor masks a penetrating insight into the heart and mind of the adolescent.  The separate chapters touch upon certain areas, attitudes, mores, and functions wherein the adolescent seems to belong to a race apart. Clothes, school, parties, cars, smoking, drinking, sex, represent some of the subjects discussed in the even-dozen chapters. Blended into the sparkling prose are numerous examples of the author's justly famous light verse.  The illustrations, which admirably catch the spirit of adolescence, complement the text and give that esthetic satisfaction we get when something seems exactly right. I can heartily recommend this book to physicians whose
Infectious and uterus related complications during pregnancy and development of atopic and nonatopic asthma in children
Authors: M. Calvani, C. Alessandri, S. Miceli Sopo, V. Panetta, S. Tripodi, A. Torre, G. Pingitore, T. Frediani, A. Volterrani
Journal: Allergy (2003)

It has been suggested that environmental factors early in life, particularly related to hygiene and infections, seem to be involved in the increase of asthma and allergic disease observed recently in developed countries. The possible effect of these factors also in utero have yet to be completely clarified. The aim of this study was to investigate the association between infective and uterus related complications during pregnancy, as well as related drug factors, with atopic and nonatopic asthma in children.This was a case-controlled study enrolling 338 children with asthma and 467 controls, who had never suffered from wheeze or asthma. Fever episodes, flu episodes, threatened abortions and related drug factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests to 10 prevalent allergens at the time of examination.Flu episodes during pregnancy were significantly associated with development of asthma in children [adjusted odds ratio (aOR) 1.91; 95% confidence interval (95% CI) 1.1-3.2], mainly with nonatopic asthma. Fever episodes showed similar results (aOR 2.16; 95% CI 1.2-3.9), but were associated with both atopic and nonatopic asthma. The effect seems mainly due to flu and fever episodes contracted in the third trimester. Exposure to isoxsuprine was significantly associated with asthma (aOR 1.54; 95% CI 1.08-2.19) while threatened abortions were more frequent in the asthma group than in controls, although the difference was statistically significant only when such events occurred in the second trimester (aOR 2.06; 95% CI 1.07-3.94). Both threatened abortions and exposure to isoxsuprine were associated only with nonatopic asthma.This study confirms that prenatal infective complications may contribute to the development of asthma in children and show a possible role for a new risk factor for asthma, that is exposure to isoxsuprine. Therefore, larger prospective studies, capable of separating atopic and nonatopic asthma, would serve to confirm these results and to explain the possible mechanism through which these factors may act.
A randomized controlled trial comparing intravesical to extravesical ureteroneocystostomy in living donor kidney transplantation recipients
Authors: Inez K.B. Slagt, Frank J.M.F. Dor, T.C. Khe Tran, Hendrikus J.A.N. Kimenai, Willem Weimar, Jan N.M. IJzermans, Türkan Terkivatan
Journal: Kidney International (2013)
Surrogate end points in clinical trials.
Authors: S. S. Ellenberg
Journal: BMJ (1991)

Warlow performed a case-control comparison of 114 patients with transient global amnesia, 109 normal community based controls, and 212 patients with transient ischaemic attacks.2The results of this careful study do not support a cerebro- vascular cause for transient global amnesia.Firstly, there were no significant differences in the prevalence of vascular risk factors between the patients with transient global amnesia and normal controls; secondly, those with transient global amnesia and those with transient ischaemic attack were not matched for vascular risk factors; and, thirdly, during follow up patients subject to transient ischaemic attacks had a much greater incidence of vascular events and a higher mortality than those subject to transient global amnesia.On the other hand, migraine was more common in those with transient global amnesia than in those in both control groups, though there were no differences in the prevalence of epilepsy.Unfortunately this information does not enable us to reach a firm conclusion about the cause of transient global amnesia, which in most cases remains uncertain.Thromboembolic disease may be the cause in a few cases, and migraine and epilepsy might account for some more.At a practical level no
Intracellular Ca2+ Fluctuations Modulate the Rate of Neuronal Migration
Authors: Hitoshi Komuro, Pasko Rakic
Journal: Neuron (1996)

Transient elevations of intracellular Ca2+ levels play critical roles in neuronal development, but such elevations have not been demonstrated in migrating neurons. Here, we show that the amplitude and frequency components of Ca2+ fluctuations are correlated positively with the rate of granule cell movement in cerebellar microexplant cultures. Moreover, depression of the amplitude and frequency components of Ca2+ fluctuations by blockade of Ca2+ influx across the plasma membrane results in a reversible retardation of cell movement. These results indicate that the combination of amplitude and frequency components of intracellular Ca2+ fluctuations may provide an intracellular signal controlling the rate of neuronal cell migration.
Diabetes Mellitus Associated with Epidemic of Infectious Hepatitis in Nigeria
Authors: F. C. Adi
Journal: BMJ (1974)

This report concerns nine cases of diabetes mellitus associated with infectious hepatitis, an epidemic of which swept through eastern Nigeria between 1970 and 1972. All the patients showed the classical symptoms and signs of diabetes. They quickly responded to treatment, and after a few months the diabetes completely disappeared. Corticosteroid-glucose tolerance tests in four patients 12 to 30 months after the remission of their diabetes were normal. Contact with the remaining five patients had been lost a few months after clinical remission of their diabetes. The infectious hepatitis virus may have damaged pancreatic islet cells to cause an acute remittant form of diabetes mellitus.
Extracellular ATP activates c-jun N-terminal kinase signaling and cell cycle progression in hepatocytes
Authors: Sundararajah Thevananther, Hongdan Sun, Duo Li, Vijaya Arjunan, Samir S. Awad, Samuel Wyllie, Tracy L. Zimmerman, John A. Goss, Saul J. Karpen
Journal: Hepatology (2004)

Partial hepatectomy leads to an orchestrated regenerative response, activating a cascade of cell signaling events necessary for cell cycle progression and proliferation of hepatocytes. However, the identity of the humoral factors that trigger the activation of these pathways in the concerted regenerative response in hepatocytes remains elusive. In recent years, extracellular ATP has emerged as a rapidly acting signaling molecule that influences a variety of liver functions, but its role in hepatocyte growth and regeneration is unknown. In this study, we sought to determine if purinergic signaling can lead to the activation of c-jun N-terminal kinase (JNK), a known central player in hepatocyte proliferation and liver regeneration. Hepatocyte treatment with ATPgammaS, a nonhydrolyzable ATP analog, recapitulated early signaling events associated with liver regeneration-that is, rapid and transient activation of JNK signaling, induction of immediate early genes c-fos and c-jun, and activator protein-1 (AP-1) DNA-binding activity. The rank order of agonist preference, UTP>ATP>ATPgammaS, suggests that the effects of extracellular ATP is mediated through the activation of P2Y2 receptors in hepatocytes. ATPgammaS treatment alone and in combination with epidermal growth factor (EGF) substantially increased cyclin D1 and proliferating cell nuclear antigen (PCNA) protein expression and hepatocyte proliferation in vitro. Extracellular ATP as low as 10 nM was sufficient to potentiate EGF-induced cyclin D1 expression. Infusion of ATP by way of the portal vein directly activated hepatic JNK signaling, while infusion of a P2 purinergic receptor antagonist prior to partial hepatectomy inhibited JNK activation. In conclusion, extracellular ATP is a hepatic mitogen that can activate JNK signaling and hepatocyte proliferation in vitro and initiate JNK signaling in regenerating liver in vivo. These findings have implications for enhancing our understanding of novel factors involved in the initiation of regeneration, liver growth, and development.
Management of Arterial Injuries Related to Cardiac Catheterization in Children and Young Adults
Authors: PETER B. MANSFIELD, ALAN B. GAZZANIGA, S. BERT LITWIN
Journal: Circulation (1970)

Retrograde arterial catheterization in children and young adults carries a risk of vessel damage and occlusion. The management of 29 such injuries is presented. The first patient in this series died after amputation of his lower extremity for gangrene. In all patients in whom distal pulses were absent 8 hours after catheterization arterial obstruction was complete. Claudication developed in the two patients who were not operated upon. Twenty-seven patients had arterial exploration and repair. The indications for exploration and the surgical technics evolved during the series are presented. In 24 patients pulses and perfusion returned to normal after operation, and two patients had residual arterial obstruction without symptoms.
Interrelationships of the Mesenchymal Diseases with Consideration of Possible Genetic Mechanisms
Authors: Raymond D. A. Peterson, Robert A. Good
Journal: Annual Review of Medicine (1963)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion
Authors: Jeroen R Huyghe, Anne U Jackson, Marie P Fogarty, Martin L Buchkovich, Alena Stančáková, Heather M Stringham, Xueling Sim, Lingyao Yang, Christian Fuchsberger, Henna Cederberg, Peter S Chines, Tanya M Teslovich, Jane M Romm, Hua Ling, Ivy McMullen, Roxann Ingersoll, Elizabeth W Pugh, Kimberly F Doheny, Benjamin M Neale, Mark J Daly, Johanna Kuusisto, Laura J Scott, Hyun Min Kang, Francis S Collins, Gonçalo R Abecasis, Richard M Watanabe, Michael Boehnke, Markku Laakso, Karen L Mohlke
Journal: Nature Genetics (2012)
Prevalence of Cardiovascular Disease Risk Factor Clustering Among the Adult Population of China
Authors: Dongfeng Gu, Anjali Gupta, Paul Muntner, Shengshou Hu, Xiufang Duan, Jichun Chen, Robert F. Reynolds, Paul K. Whelton, Jiang He
Journal: Circulation (2005)

The prevalence of cardiovascular disease (CVD) risk factors has been increasing in China.We examined the prevalence of CVD risk factor clustering among Chinese adults aged 35 to 74 years with data from the International Collaborative Study of Cardiovascular Disease in Asia (InterAsia), a cross-sectional survey of a nationally representative sample (n=14 690) conducted during 2000 to 2001 and compared these data with those of US adults from the National Health and Nutrition Examination Survey of 1999 to 2000. Overall, 80.5%, 45.9%, and 17.2% of Chinese adults had > or =1, > or =2, and > or =3 modifiable CVD risk factors (dyslipidemia, hypertension, diabetes, cigarette smoking, and overweight), respectively. By comparison, 93.1%, 73.0%, and 35.9% of US adults had > or =1, > or =2, and > or =3 of these risk factors, respectively. In a multivariate model including age, sex, and area of residence, the odds ratio (95% confidence interval [CI]) of having > or =1, > or =2, and > or =3 CVD risk factors versus none of the studied risk factors was 2.61 (95% CI, 2.09 to 3.27), 3.55 (95% CI, 2.77 to 4.54), and 4.97 (95% CI, 3.67 to 6.74), respectively, for Chinese adults 65 to 74 years old versus 35 to 44 years old; 3.65 (95% CI, 3.21 to 4.15), 4.67 (95% CI, 4.06 to 5.38), and 5.60 (95% CI, 4.70 to 6.67), respectively, for men compared with women; 1.18 (95% CI, 1.07 to 1.30), 1.34 (95% CI, 1.21 to 1.50), and 1.84 (95% CI, 1.60 to 2.12), respectively, for urban compared with rural residents; and 1.98 (95% CI, 1.76 to 2.22), 2.75 (95% CI, 2.42 to 3.13), and 4.36 (95% CI, 3.68 to 5.18), respectively, for residents of northern compared with southern China.Clustering of CVD risk factors is common in China. Prevention, detection, and treatment of CVD risk factor clustering should be an important component of a national strategy to reduce the increasing burden of CVD in China.
Ig Nobel awards celebrate studies of motion sickness, bladder control, and a mayor with an armoured tank
Authors: J. Lenzer
Journal: BMJ (2011)

If you’ve ever wondered why discus throwers but not hammer throwers become dizzy while spinning, then wonder no more. “Hammer throwers, like ballet dancers and figure skaters, use “gaze fixation [which] permits post-rotatory nystagmus inhibition,” said Philippe Perrin, who with his team of researchers from the Netherlands and France was awarded the 2011 Ig Nobel physics prize for solving the motion sickness mystery.

Medical topics dominated the 21st Ig Nobel prize ceremony this year. The awards, which honour science that “first makes you laugh, then makes you think,” were given out by genuine Nobel laureates at Harvard University on 29 September.

Professor Perrin, professor of physiology and balance control at Nancy University, France, and a physician in otolaryngology, told the BMJ that gaze fixation, …