tbuckley/cabot-search huggingface dataset:
N-Terminal Pro–B-Type Natriuretic Peptide Levels for Dynamic Risk Stratification of Patients With Acute Coronary Syndromes
Authors: Christopher Heeschen, Christian W. Hamm, Veselin Mitrovic, Nicte-Ha Lantelme, Harvey D. White
Journal: Circulation (2004)

Background— Elevated baseline levels of B-type natriuretic peptide (BNP) and the N-terminal fragments of its prohormone, N-terminal-pro-BNP (NT-proBNP), have been associated with adverse long-term outcome in patients with acute coronary syndromes, whereas the prognostic implications of serial NT-proBNP measurements have not been investigated to date. Methods and Results— NT-proBNP, troponin T, and C-reactive protein were measured at baseline and at 48 and 72 hours in 1791 patients with non–ST-elevation acute coronary syndromes. Death and myocardial infarction were recorded during 30 days of follow-up. After adjustment for independent predictors of cardiac risk, baseline NT-proBNP levels &gt;250 ng/L were associated with higher event rates (adjusted OR, 3.7; 95% CI, 2.3 to 5.7; P &lt;0.001). In troponin T–negative patients, NT-proBNP identified a subgroup of high-risk patients (OR, 5.9; 95% CI, 2.6 to 13.3; P &lt;0.001). The risk in those patients (7.2%) did not significantly differ from that in troponin T–positive patients (9.8%; P =0.25). Importantly, clinical stabilization without refractory ischemia was associated with a rapid (as soon as 48 hours after onset of symptoms) and significant (48 hours; −24%; 72 hours, −49%; both P &lt;0.001) decline in NT-proBNP levels. In patients with high NT-proBNP baseline levels, lack of a rapid decline in NT-proBNP levels (≤250 ng/L) was linked to an adverse short-term prognosis (OR, 33.7; 95% CI, 8.2 to 138.8; P &lt;0.001). In patients with low NT-proBNP baseline levels, a rise in NT-proBNP levels over 72 hours to &gt;250 ng/L was also linked to an adverse 30-day prognosis (OR, 24.0; 95% CI, 8.4 to 68.5; P &lt;0.001). Conclusions— Neurohumoral activation as evidenced by NT-proBNP appears as a unifying feature that is independent of other biochemical markers (myocardial necrosis, inflammation) and is a powerful and independent determinant of the short-term cardiac risk in patients with acute coronary syndromes. Whether serial measurements of NT-proBNP in patients with ACS may be used to more rapidly identify patients suitable for early discharge or more intensive therapy deserves future prospective studies.
Abstract 5267: STAT signaling is totally deregulated in malignant pleural mesothelioma: What are the reasons.
Authors: Lisa Arzt, Franz Quehenberger, Iris Halbwedl, Helmut H. Popper
Journal: Cancer Research (2013)

Abstract Malignant pleural mesothelioma (MPM) is an aggressive tumor caused by former asbestos exposure with a mean overall survival of 12 months from diagnosis. The knowledge about predictive factors of outcome is poor and MPM is resistant to conventional therapy. The long latency period in MPM pathogenesis as well as the absence of early symptoms is responsible for the late diagnosis of this disease. From our recent study and published data we know that the regular rapid progressive type of MPM uses several signaling pathways regulating cell growth and survival. Asbestos causes genetic modifications, most notably the upregulation of cell survival and growth signaling pathways as well as the expression of other proteins that favor the resistance of MPM to apoptosis and chemotherapy. In order to develop more effective therapy than the currently used chemotherapy, novel targets have to be identified in MPM. The JAK/STAT signaling pathway is the principal signaling mechanism for lots of cytokines or growth factors in mammalians. JAK activation induces a variety of biological responses like cell proliferation, differentiation, cell migration, and apoptosis. Our investigations demonstrate that the STAT signaling pathway is totally deregulated: STAT1 is upregulated, whereas STAT3 is downregulated. SOCS1 and SOCS3 - which represent a negative feedback loop and which are regulators of STAT1 and STAT3 - are totally missing in MPM. Investigations in six mesothelioma cell lines showed that STAT1 is highly expressed and that SOCS1 is missing whereas the expression of pSTAT1 (Tyr701) can be stimulated and therefore be increased by Interferon-gamma treatment. The expression levels of other components of the STAT signaling pathway in these cell lines are currently under investigation. It is known that protein expression is controlled by noncoding RNAs, e.g. microRNAs (miRNA) and we investigated the possible impact of miRNAs on the STAT signaling pathway in MPM. We identified miR-30d* as a regulator of phosphorylated STAT1 (Ser727). Furthermore we found that miR-19b, miR-30b, miR-30c and miR-222 are upregulated which are predicted to target SOCS1 and SOCS3 - this could be an explanation for the missing expression of these proteins. MiR-21 is extremely upregulated in MPM, a miRNA that is associated with a wide variety of human tumors and which targets STAT3. Understanding the role of STATs in MPM could be the first step into the development of a targeted therapy for these tumors. Citation Format: Lisa Arzt, Franz Quehenberger, Iris Halbwedl, Helmut H. Popper. STAT signaling is totally deregulated in malignant pleural mesothelioma: What are the reasons. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5267. doi:10.1158/1538-7445.AM2013-5267
EFFECT OF INFECTION WITH M. TUBERCULOSIS AND OF TUBERCULIN SHOCK ON THE SUCCINIC DEHYDROGENASE ACTIVITY OF GUINEA PIG TISSUES
Authors: S. N. Chaudhuri, Samuel P. Martin
Journal: The Journal of Experimental Medicine (1953)

The kidney of guinea pigs infected with the H37Rv and BCG strains of M. tuberculosis showed a diminution in succinic dehydrogenase activity when measured by the tetrazolium technique. This effect was also seen in the liver and spleen of animals infected with the BCG strain. Sensitized animals showed similar results when given tuberculin in sublethal doses. The succinic oxidase was also low in the kidneys of animals infected with the H37Rv strain. The depressed enzyme activity of the tissues of infected animals could be restored to normal by addition of normal tissue extract or dialysate. This suggests that the alteration in tissue metabolism observed in tuberculosis may depend upon the loss of some as yet unidentified factor important for succinic dehydrogenase activity.
LATE–ACQUIRED INCOMPLETE STENT APPOSITION AFTER EVEROLIMUS–ELUTING STENT VERSUS SIROLIUMS–ELUTING STENT IMPLANTATION IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION (APPOSITION–AMI)
Authors: Seung–Ho Hur, Jihyun Sohn, Yun–Kyeong Cho, Hyuck–Jun Yoon, Hyungseop Kim, Chang–Wook Nam, Bong–Ryull Lee, Sang–Wook Kim, Young Joon Hong, Jang–Ho Bae, Donghoon Choi, Hyun–Jae Kang, So–Yeon Choi, Sang Gon Lee, Doo–Il Kim, Jong–Sun Park, Seung Woon Rha, Kwon–Bae Kim
Journal: Journal of the American College of Cardiology (2013)
Breast surgeon is investigated by GMC over allegations of unnecessary surgery
Authors: C. Dyer
Journal: BMJ (2012)

A surgeon under investigation by the UK General Medical Council over allegations that he carried out more than 1000 unnecessary or inappropriate breast cancer operations also faces a possible police inquiry.

Ian Stuart Paterson is accused of performing unnecessary lumpectomies on up to 450 women without first carrying out a biopsy and of doing “cleavage sparing” mastectomies on up to 700 women that risked leaving cancerous tissue behind. He was suspended from practice last month by the Medical Practitioners Tribunal Service, pending a full hearing into the charges next summer.

Paterson worked at NHS and …
The Surgical Treatment of Portal Hypertension, Bleeding Esophageal Varices and Ascites
Authors: Jerome M. Silver
Journal: JAMA (1961)

The physiology, pathophysiology, pathogenesis, and therapy of portal hypertension, with its attendant complications, are in a constant state of flux. This becomes abundantly evident when one views the current literature and discovers that there are several theories regarding the pathogenesis of this condition, coupled with numerous approaches to the solution of its sequelae. In his monograph, the author has proceeded in an orderly manner to place under one cover all the present theories, knowledge, and treatments of portal hypertension and its complications. The book opens with a superficial study of the physiological considerations in the production of portal hypertension and ascites and a discussion of extraand intra-hepatic obstructions. Diagnostic methods used to determine one of the most dramatic complications of portal hypertension, namely, bleeding esophageal varices, are presented. The main body of the book concerns itself with the surgical correction of portal hypertension. The description of the techniques are excellent
Hydroxyurea, Leucopheresis, and Splenectomy in Chronic Myeloid Leukaemia at the Problastic Phase
Authors: L. Schwarzenberg, G. Mathe, P. Pouillart, R. Weiner, J. Locour, J. Genin, M. Schneider, F. De Vassal, M. Hayat, J. L. Amiel, J. R. Schlumberger, C. Jasmin, C. Rosenfeld
Journal: BMJ (1973)

Forty-three patients with chronic myeloid leukaemia have been treated with hydroxyurea in order to be subjected to leucopheresis for white cell transfusions. Hydroxyurea decreases leucocytosis when it is administered and the blood granulocyte number increases soon after the drug is stopped. The survival of the patients is not different from the survival of the patients treated with conventional chemotherapy (busulphan, mitobronitol) and it is superior to the survival of patients treated with external radiotherapy or with <sup>32</sup>P. Half of the patients were subjected to splenectomy during first remission for a phase II trial. They were not randomized, but the distribution according to age was similar in the two groups. A slight difference appears in favour of splenectomy so far as survival is concerned, but there were three post-operative deaths out of 18 patients. We conclude that a phase II trial on the value of splenectomy is indicated ethically, but that the patients should be operated on and nursed in a microbiologically controlled environment.
CARCINOMA AND TUBERCULOSIS TREATED BY THE ROENTGEN RAYS.
Authors: G. E. PFAHLER
Journal: JAMA (1903)

safely and easily do the major operation later by the abdominal route and save many lives in that way.Db. D. H. Ceaiq, Boston-I think cutting through a wall S to 10 cm. in thickness should be kept distinctly out of the field of vaginal opening.When we have pus so firmly walled off as that it is perfectly safe to go through the abdominal wall, then we can clean it out thoroughly and make a com¬ plete cure instead of leaving the patient with a lot of material to absorb.As regards the occasional operator, I think the vaginal route is better for him, providing he is sure of his technic.But no man can do more harm than the occasional operator going through Douglas' cul-de-sac into the abdomen.The posterior or anterior cul-de-sac operations are not, as a rule, curative.They are palliative, and if the occasional operator will take that route and do these operations it is incumbent on him to advise his patient of the fact that he is doing a palliative operation and that other work may be required by some one who is not an occasional operator.Dr. J. II.Carstens, Detroit-I wish the essayist would say "opening" instead of "puncture."A "puncture" means a little bit of an opening, and to my mind the opening can not be too big.A little one closes up right away, and you must do your work again.Make a good, big opening, and give Nature a chance.Dk. C. O. Thienhaus-When I have a hard mass lying in the cul-de-sac of Douglas, and the diagnosis, whether or not this hard mass contains a focus of pus, can not be ascer¬ tained by other means, I advocated in my paper exploratory vaginal puncture for this purpose, and if 1 find pus I drain
Maternal-Fetal Transmission of HIV-1-Reply
Authors: Yvonne J. Bryson
Journal: JAMA (1995)

<h3>In Reply.</h3> —Dr Sarkar points out that multivariate analysis of the potential factors associated with maternal-fetal transmission would be preferable to a univariate analysis. We agree. However, because of the small sample size of our cohort and the large number of variables, this was not possible and would have added nothing to our results. We hope that as our cohort size increases this will become possible. We analyzed all of the factors outlined in Table 2 of the original article stratified for zidovudine use. As discussed in the article, we found that the observations of increased transmission risk, associated both with exposure to maternal blood and with the presence of maternal p24 antigemia, were even more significant in the zidovudine-untreated mothers. The problem of dealing with the analysis of results based on infant outcome in multiple pregnancies and twins is difficult, but we based our assumptions on the fact that
Diagnosis and current treatments for primary iron overload
Authors: Pierre Brissot
Journal: American Journal of Hematology (2007)

Primary iron overload encompasses a variety of genetic iron overload syndromes, dominated in frequency by HFE-related, or Type 1 hemochromatosis, for which French diagnostic and therapeutic guidelines have been recently proposed. Differential diagnosis of Type 1 hemochromatosis can be made from both clinical data and genetic studies. Venesection therapy and family screening remain the basis for the curative and preventive management of most genetic iron overload diseases.
Tethering Naturally Occurring Peptide Toxins for Cell-Autonomous Modulation of Ion Channels and Receptors In Vivo
Authors: Inés Ibañez-Tallon, Hua Wen, Julie M. Miwa, Jie Xing, Ayse B. Tekinay, Fumihito Ono, Paul Brehm, Nathaniel Heintz
Journal: Neuron (2004)
Antigen-specific effector CD8 T cells regulate allergic responses via IFN-γ and dendritic cell function
Authors: Yafang Tang, Shou Ping Guan, Benson Y.L. Chua, Qian Zhou, Adrian W.S. Ho, Kenneth H.S. Wong, Kok Loon Wong, W.S. Fred Wong, David M. Kemeny
Journal: Journal of Allergy and Clinical Immunology (2012)
FURTHER STUDIES OF THE INFECTIOUS UNIT OF VACCINIA
Authors: R. F. Parker, L. H. Bronson, R. H. Green
Journal: The Journal of Experimental Medicine (1941)

A study has been made of the comparative virulence of several strains of vaccine virus for a number of hosts, and wide variation in animal susceptibility has been demonstrated. The results obtained in experiments with a chick-embryo-adapted strain are interpreted as indicating that the particles of virus are of essentially uniform virulence. Results of statistical analyses are presented which indicate that as the virulence of a strain of virus increases the number of elementary bodies per infectious unit approaches 1, and at that limit the chance of infection is governed primarily by the presence or absence of virus in the inoculum. With lower virulence the chance of a lesion following inoculation of virus is still described by the binomial theorem, but the actual distribution is primarily of susceptible cells not of viral particles. It is postulated that with regard to the proportion of cells available for parasitism, differences exist between different animals of a species, and that this distribution is of a normal character.
US healthcare executive pays back $600m in stock options case
Authors: Janice Hopkins Tanne
Journal: BMJ (2008)

A Nigerian judge has ordered the arrests of three Pfizer officials for failing to attend court to respond to criminal charges against Pfizer for treating children with an experimental drug during a deadly meningitis outbreak in Kano, Nigeria, in 1996.Judge Shehu Atiku in Kano ordered arrest warrants for the head of Pfizer in Nigeria, Ngozi Edozien, and the senior officials Lare Baale and Segun Donguro, after they failed to attend court on 6 November.Government prosecutors in Nigeria say that Pfizer used critically ill children as "guinea pigs" to study Pfizer's experimental drug trovafloxacin.Four separate legal actions have been filed in Nigeria against Pfizer, including 31 criminal counts against 10 people.Plaintiffs seek a total of $9bn (£4.5bn; €6bn) in civil suits.Pfizer says that it will "vigorously defend itself against the 'untrue allegations' in the government's lawsuits," and it says that the children died from meningitis and not from the drugs.In response to the
COMPLETE DISLOCATION OF TARSAL SCAPHOID
Authors: SAUL BERMAN
Journal: JAMA (1924)

Complete dislocation of the tarsal scaphoid is very uncommon; therefore, a report of a case may be of interest. <h3>REPORT OF CASE</h3> J. C., a youth, aged 17, a milk man, was riding horseback, Nov. 3, 1922, when the horse tripped over a car track, fell, and landed on the patient's right foot. His foot was caught in the track, and when the horse struck it he felt something in his foot "give." He was unable to walk, and was brought at once to the hospital. On admission, the entire foot was considerably swollen, and along the inner surface, from the base of the first metatarsal to the internal malleolus, there was marked ecchymosis. The pain was intense. All active motions were absent, and on passive motion no crepitus could be felt. On the inner aspect, alongside the head of the astragalus, a distinct protuberance was noted. The swelling obliterated
Embryotoxicity of the alkylphenol degradation product 4-nonylphenol to the crustacean Daphnia magna.
Authors: G A LeBlanc, X Mu, C V Rider
Journal: Environmental Health Perspectives (2000)

Laboratory studies have suggested that some alkylphenols and pesticides elicit developmental toxicity to crustaceans. The purpose of the present study was to evaluate the possibility that the alkylphenol degradation product 4-nonylphenol is embryotoxic to the crustacean Daphnia magna through its known ability to interfere with the metabolic elimination of testosterone. Direct exposure of maternal daphnids to testosterone caused developmental abnormalities in neonates that consisted of partial arrest of early embryonic development and abnormalities in shell spine and first antennae development. Exposure of maternal daphnids to concentrations of 4-nonylphenol also produced developmental abnormalities though the profile of abnormalities was distinct from that observed throughout the testosterone concentration-response curve. Thus, 4-nonylphenol is a developmental toxicant in daphnids, but its toxicity is not consistent with that elicited by elevated testosterone accumulation. Further experiments demonstrated that testosterone was directly toxic to developing embryos, and the maternal organism can serve as the vector for this toxicity. In contrast, neither direct embryo exposure nor early maternal exposure to 4-nonylphenol elicited embryotoxicity consistent with that observed during continuous maternal and gestational exposure. Thus, 4-nonylphenol is not directly embryotoxic at these exposure levels, but rather toxicity is mediated by maternal influences during gestation. The threshold concentration for the occurrence of developmental abnormalities ( approximately 44 microg/L) indicates that typical environmental concentrations of 4-nonylphenol pose no imminent hazard with respect to developmental toxicity. However, these effects do occur at sufficiently low levels to warrant evaluation of the relative susceptibility of other crustacean species to this previously uncharacterized mode of toxicity.
ASSESSMENT OF DUAL ANTIPLATELET RESPONSIVENESS WITH THE POINT-OF-CARE DEVICE VERIFYNOW AFTER PERCUTANEOUS CORONARY INTERVENTION IN ELDERLY PATIENTS (≥75 YEARS)
Authors: A M Tidjane, R. Ghenim, V. Bongard, N. Boudou, N. Dumonteil, N. Hammami, A. Ziani, J. Roncalli, Th Lhermusier, P. Sié, D. Carrié
Journal: Journal of the American College of Cardiology (2010)
Abstract 5538: Sarcomas in TP53 germline mutation carriers
Authors: Simona Ognjanovic, Magali Olivier, Tracy L. Bergemann, Pierre Hainaut
Journal: Cancer Research (2011)

Abstract Sarcoma plays a central role in Li-Fraumeni syndrome (LFS) definition. Germline mutations in TP53 gene underlie this rare familial syndrome and are detected in over 80% of LFS patients. The International Agency for Research on Cancer (IARC) maintains a database of germline TP53 mutations that collects published data on LFS and related syndromes and provides baseline information about TP53 mutation prevalence and phenotype in these patients. We analyzed the characteristics of germline TP53 germline mutations in LFS and related syndrome patients with sarcoma using the IARC TP53 Database. The prevalence of individual sarcoma types and their age/gender distribution in TP53 mutation carriers were compared to sporadic sarcomas in Caucasians obtained by SEER registry analysis using the SEERStat program. Sarcoma represented 25% of all tumors diagnosed in TP53 carriers in this study. We confirmed young age of sarcoma onset among carriers, with 95.6% of cases diagnosed before the age of fifty years, as opposed to 38.3% of sporadic cancer. Carriers had increased risk for osteosarcoma in both children/adolescents and adults (OR=1.41, 95% CI=1.02-1.94, and OR=4.61, 95% CI=2.72-7.83), while increased risk for rhabdomyosarcoma was confined to carriers younger than 5 years (OR=11.6, 95%CI=6.1-21.9, p&amp;lt;0.00001). Analysis of the association of mutations with specific sarcoma types revealed that mutations in the oligomerization domain (codon 344 and 337) increased the risk of leiomyosarcoma (OR=10.1, 95% CI=3.4-29.9). Analysis of codons most frequently mutated in sarcoma showed that four codons (220, 275, 282, 344) were associated with 3-fold increased risk of sarcoma, compared to other cancers in TP53 carriers. In conclusion, this study provided further evidence for genotype-phenotype correlations in germline TP53 mutations carriers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5538. doi:10.1158/1538-7445.AM2011-5538
Foetal Erythrocytes in the Maternal Circulation
Authors: E. S. Brown
Journal: BMJ (1963)

MEDIBRCJmLJOURNthe hair turned from dark brown to blonde in three months when the patients were taking 20 tablets (10 g.) daily.There were no general ill-effects and the colour change was much appreciated by the four women patients, who seemed inclined to keep it a secret.The manner in which mephenesin exerts this effect on melanogenesis is not known, but experimental studies are being undertaken.
SELECTIVE INHIBITION OF THE MASTER REGULATOR TRANSCRIPTION FACTOR EGR-1 USING CATALYTIC OLIGONUCLEOTIDES REDUCES MYOCARDIAL INJURY AND IMPROVES LV SYSTOLIC FUNCTION IN A PRECLINICAL MODEL OF MYOCARDIAL INFARCTION
Authors: Benjamin Rayner, Gemma Figtree, William Lay, Tharani Sabaretnam, Ping Shang, Jawad Mazhar, James Weaver, Stuart Grieve, Stephen Hunyor, Levon Khachigian, Ravinay Bhindi
Journal: Journal of the American College of Cardiology (2013)