tbuckley/cabot-search huggingface dataset:
Buffer Solutions May Compromise Cardiac Resuscitation by Reducing Coronary Perfusion Pressure
Authors: Fulvio Kette
Journal: JAMA (1991)

<h3>Objective.</h3> —To investigate the effects of hypertonic buffer solutions on coronary perfusion pressure (CPP) and resuscitability during experimental closed-chest cardiac resuscitation. <h3>Design.</h3> —Randomized, placebo-controlled trial. <h3>Setting.</h3> —Mammalian research laboratory. <h3>Participants.</h3> —Forty-four domestic pigs. <h3>Interventions.</h3> —Cardiac arrest was induced by ventricular fibrillation in mechanically ventilated pigs anesthetized with pentobarbital sodium. Precordial compression was started at the third minute of untreated ventricular fibrillation and maintained for an interval of 8 minutes. A hypertonic solution of sodium bicarbonate, Carbicarb (an equimolar mixture of sodium bicarbonate and sodium carbonate [International Medication Systems, Ltd]), or sodium chloride or an isotonic solution of sodium chloride was infused into the right atrium over a 1-minute interval starting at the sixth minute of ventricular fibrillation. Restoration of spontaneous circulation was attempted by DC transthoracic countershock after 11 minutes of ventricular fibrillation. <h3>Main Outcome Measures.</h3> —Plasma osmolality, CPP, and cardiac resuscitability. <h3>Results.</h3> —Infusion of hypertonic buffer and sodium chloride solutions increased plasma osmolality from an average of 280 to 330 mOsm/kg. This was accompanied by a significant decrease in the aortic pressures and CPPs generated during precordial compression. No such changes occurred after infusion of isotonic sodium chloride. Restoration of spontaneous circulation, as in earlier studies, was contingent on the levels of CPP prior to attempted defibrillation. Accordingly, none of 13 animals in which the CPP declined to less than 10 mm Hg after infusion of the hypertonic solutions were successfully resuscitated. This contrasted with nine animals that received isotonic sodium chloride and served as controls. Coronary perfusion pressure consistently exceeded 10 mm Hg in these control animals, and spontaneous circulation was restored in each instance. <h3>Conclusions.</h3> —Hypertonic solutions and specifically buffer solutions administered in the absence of vasopressor agents may adversely affect cardiac resuscitation efforts by reducing CPP below critical thresholds. (<i>JAMA</i>. 1991;266:2121-2126)
Healthcare workers and patients demonstrate against privatisation in Madrid's health service
Authors: M. Jara
Journal: BMJ (2009)

A coalition of health professionals and patients is to demonstrate in Madrid next week against increasing privatisation in the capital’s public healthcare system.

The coalition, called the Coordinadora Anti-privatizacion de Madrid, condemns the People’s Party government of the president of Madrid, Esperanza Aguirre, for “developing a healthcare model that dismantles, slowly but surely, the public healthcare system to offer large benefits to construction, finance, and health insurance companies,” said Juan Antonio Gomez Liebana, a nurse, sociologist, and member of the coalition.

Since 2004 Mrs Aguirre’s government has been promoting a private finance initiative, …
CARDIAC OUTPUT PREDICTS THE IMPROVEMENT OF RIGHT VENTRICULAR FUNCTION AFTER MITRACLIP IMPLANTATION IN PATIENTS WITH SECONDARY MITRAL REGURGITATION
Authors: Felix Kreidel, Hannes Alessandrini, Christian Frerker, Thomas Thielsen, Marco Marzullo, Ulrich Schaefer, Karl-Heinz Kuck
Journal: Journal of the American College of Cardiology (2014)
The Liver: Biology and Pathobiology
Authors: Frank Iber
Journal: JAMA (1994)

Each six years, the surge of new information has fully justified a new edition of this book. It continues to provide the advances of fundamental biology in a framework that applies them to liver structure, function, and disease for both clinicians and bench scientists. The current edition has 10 totally new chapters, and more than 60% of the remaining material has been almost totally rewritten. Among the nearly 90 authors are 24 full professors and an equal number of graduate students and fellows, indicating that the workers producing the new information have written this book under the careful guidance of the many editors, with Nelson Fausto and James Boyer being new to this edition. A little better than half the authors have the MD degree. The book is organized into six highly unequal sections. The largest and best consists of 45 chapters on the cells of the liver and how
MB-19 * MEDULLOBLASTOMA SUBTYPES SPECIFY INTER-TUMORAL VASCULAR BLOOD BRAIN BARRIER HETEROGENEITY
Authors: T. Phoenix, D. Patmore, S. Boop, M. Jacus, Y. Patel, L. Goumnerova, S. Perreault, E. Wadhwa, Y.-J. Cho, C. Stewart, R. Gilbertson
Journal: Neuro-Oncology (2015)

Medulloblastoma is the most common malignant childhood brain tumor, consisting of four molecularly and clinically distinct subtypes. Recent work has advanced our understanding about the basic pathological processes, identifying unique mutations and anatomical locations that contribute to medulloblastoma subtype heterogeneity. Recognizing how subtype-specific genetic alterations dictate treatment response is critical to advancing treatments for all patients. The central nervous system (CNS) contains a unique vascular system that tightly regulates exchange between the blood and brain, termed the blood brain barrier (BBB). How brain tumors specify BBB properties in newly formed blood vessels, and if this dictates tumor behavior remains unanswered. Here we show that WNT-subtype medulloblastomas create a microenvironment that inhibits BBB formation, producing tumors with a highly permeable aberrant vascular network. We found human and mouse WNT-subtype tumors display increased vascularization and hemorrhaging, along with decreased expression of endothelial BBB associated genes. Fenestrated blood vessels, normally associated with peripheral organs, are highly enriched in WNT-subtype tumors, allowing unrestricted exchange of substances between blood and tumor. Canonical Wnt signaling is essential for normal CNS BBB formation and maintenance. WNT-subtype tumors express high levels of secreted Wnt antagonists, creating a microenvironment that is inhibitory to canonical Wnt signaling and BBB formation in neighboring endothelial cells. Differences in BBB status between WNT and SHH-subtype tumors result in differential in vivo treatment response and drug penetration, suggesting the abnormal vasculature might contribute to the excellent clinical prognosis associated with WNT-subtype patients. Our data offer insight into brain tumor-vascular BBB specification, and should benefit ongoing efforts to improve response, survival, and quality of life for all medulloblastoma patients.
Principles of Behavioral Neurology
Authors: Sam U. Ho
Journal: JAMA (1986)

This 405-page book by Mesulam and 12 other authors is extremely well organized. Mesulam first introduces the concepts of neuroanatomy and neurophysiology with behavioral correlation. Following are five chapters of in-depth analysis of attention, memory, language, affect, and perceptual processes. The overview of mental-state assessment (chapter 2) is invaluable to clinicians. Each section is written succinctly, with detailed clinical cases and diagrams for illustration. The bibliographies presented at the ends of chapters are carefully chosen and upto-date. The last three chapters drill on the applications of recent medical technologies. In the near future, radiologic, magnetic, and metabolic imagings and electrophysiology will give us further insight into the subject of behavioral neurology. I recommend this book; it brings together a wide range of current concepts in a single compact and well-edited volume.
Abstract 4090: The role of caspase-2 in apoptotic signaling in AML cells
Authors: Petra Haag, Marita Lagergren Lindberg, Lena Kanter, Leif Stenke, Rolf Lewensohn, Kristina Viktorsson
Journal: Cancer Research (2011)

Abstract We are investigating signaling molecules involved in apoptotic cell death in acute myeloid leukemia (AML) cells after treatment with the targeted drug gemtuzumab ozogamicin (GO) and the conventional drug daunorubicin, with focus on caspase-2. New effective therapeutic drugs are highly desirable in the treatment of AML. Although a majority of treated patients initially respond to conventional treatment, most patients will relapse within 1-2 years. Also, the treatment is associated with severe off-target effects. GO is a novel therapeutic approach, consisting of a monoclonal CD33 antibody coupled to calicheamicin, which cause DNA double strand breaks (DSB). We demonstrated that activation of Bak and Bax is critical for GO- and daunorubicin- induced apoptotic signaling in AML cells. The activation was followed by mitochondrial depolarization, caspase-3 activation and nuclear fragmentation. We continued to examine potential proapoptotic signaling events upstream of mitochondria in HL60 AML cells in vitro. We identified caspase-2 and the pro-apoptotic BH3-only protein Bid as two candidates. By analyzing caspase-2 by western blotting after GO treatment we found that GO caused cleavage of caspase-2 after 24h, which was prior to mitochondria-mediated signaling. Also, full-length Bid was cleaved to its truncated, active form tBid. The importance of caspase-2 activation in the signaling cascade after GO treatment was demonstrated using z-VDVAD-fmk, a caspase-2 inhibitor. Preincubation with this inhibitor reduced caspase-3 activation with around 50%, suggesting that caspase-2 is an important molecule, located upstream of caspase-3, in the signaling between DNA double stranded breaks and apoptosis signaling in AML cells. In conclusion, we demonstrate that GO and daunorubicin, at clinically applicable concentrations, induce pro-apoptotic signaling which involve activation of caspase-2, and activation of the BH3-only protein Bid. Blocking caspase-2 activity reduced caspase-3 activation with 50%. This suggests multiple signaling pathways capable of activating caspase-3. The caspase-2 pathway appears central for downstream caspase-3 activity, after GO treatment in AML. Our findings may highlight possible resistance mechanisms in AML, which might have profound therapeutic implications. 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 4090. doi:10.1158/1538-7445.AM2011-4090
Grooved Director for Vaginal Hysterectomy. Uterine Elevating Forceps.
Authors: E. D. FERGUSON
Journal: JAMA (1900)

Though simplicity and fewness of instruments in operative work is the pride of many surgeons, there can be no question concerning the help that most operators find in special devices to meet special indications. The two instruments which I present have been tested in actual work and have been found helpful. The first which I show is a director intended to be passed behind the broad ligament in vaginal hysterectomy, thereby bringing at once into the operative field, and in full view of the operator, the lateral tissues to be incised. Having opened freely into the pouch of Douglas and having freed the bladder from the uterus, the left index finger of the operator is passed behind the broad ligament and made to appear above that structure at the side of the uterus, the peritoneum having been incised previously at the corresponding vesical fold, or the opening being made on
Outbreak of Japanese encephalitis hits Malaysia
Authors: A. Easton
Journal: BMJ (1999)

More than 50 people have died and hundreds of thousands of pigs-the possible carriers of the infection-have been slaughtered in Malaysia after an outbreak of Japanese encephalitis.

There have been 154 reported cases of Japanese encephalitis, of which 42 have been confirmed, and 56 deaths in Negeri Sembilan, 90 km south of the capital, Kuala Lumpur, and in Perak. Many of the victims were adult …
Hepatitis C virus reinfection and superinfection among treated and untreated participants with recent infection
Authors: Jason Grebely, Son Truong Pham, Gail V. Matthews, Kathy Petoumenos, Rowena A. Bull, Barbara Yeung, William Rawlinson, John Kaldor, Andrew Lloyd, Margaret Hellard, Gregory J. Dore, Peter A. White
Journal: Hepatology (2011)

The purpose of the study was to evaluate reinfection and superinfection during treatment for recent hepatitis C virus (HCV). The Australian Trial in Acute Hepatitis C (ATAHC) was a prospective study of the natural history and treatment of recent HCV. Reinfection and superinfection were defined by detection of infection with an HCV strain distinct from the primary strain (using reverse-transcription polymerase chain reaction [RT-PCR] and subtype-specific nested RT-PCR assays) in the setting of spontaneous or treatment-induced viral suppression (one HCV RNA <10 IU/mL) or persistence (HCV RNA >10 IU/mL from enrollment to week 12). Among 163 patients, 111 were treated, 79% (88 of 111) had treatment-induced viral suppression, and 60% (67 of 111) achieved sustained virological response. Following treatment-induced viral suppression, recurrence was observed in 19% (17 of 88), including 12 with relapse and five with reinfection (4.7 cases per 100 person-years [PY], 95% confidence interval [CI]: 1.9, 11.2). Among 52 untreated patients, 58% (30 of 52) had spontaneous viral suppression and recurrence was observed in 10% (3 of 30), including two with reinfection. Following reinfection, alanine aminotransferase (ALT) levels >1.5× the upper limit of normal were observed in 71% (5 of 7). Among 37 with persistence, superinfection was observed in 16% (3 of 19) of those treated and 17% (3 of 18) of those untreated. In adjusted analysis, reinfection/superinfection occurred more often in participants with poorer social functioning at enrollment and more often in those with ongoing injecting drug use (IDU).Reinfection and superinfection can occur during treatment of recent HCV and are associated with poor social functioning and ongoing IDU. ALT levels may be a useful clinical marker of reexposure.
Eruptive melanocytic nevi in patients with renal allografts: Report of 10 cases with dermoscopic findings
Authors: Mauro Alaibac, Stefano Piaserico, Carlo Riccardo Rossi, Mirto Foletto, Gabriella Zacchello, Paolo Carli, Anna Belloni-Fortina
Journal: Journal of the American Academy of Dermatology (2003)
Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival
Authors: Abul Kalam Azad, Isabelle Bairati, Elodie Samson, Dangxiao Cheng, Maryam Mirshams, Xin Qiu, Sevtap Savas, John Waldron, Changshu Wang, David Goldstein, Wei Xu, Francois Meyer, Geoffrey Liu
Journal: Clinical Cancer Research (2011)

Abstract Purpose: From the published literature, we identified 23 germ line sequence variants in 17 genes from hypothesis-generating studies that were associated with prognosis of head and neck cancer, including sequence variants of DNA repair (ERCC1, ERCC4, ERCC5, MSH2, XPA, ERCC2, XRCC1, XRCC3), DNA methylation (DNMT3B), cell cycle and proliferation (CCND1, TP53), xenobiotic metabolism (GSTM1, GSTT1, CYP2D6), metastatic -potential (MMP3), immunologic (CTLA4), and growth factor pathways (FGFR4). The purpose of this study was to validate the role of these 23 sequence variants for overall (OS) and disease-free survival (DFS) in a large, comprehensive, well-annotated data set of patients with head and neck cancer. Experimental Design: We genotyped these sequence variants in 531 patients with stage I and II radiation-treated head and neck cancer (originally recruited for an alpha-tocopherol/beta-carotene placebo-controlled secondary prevention study), and analyzed using Cox proportional hazards models, stratified by treatment arm, adjusting for clinical prognostic factors. Results: Two OS associations were statistically significant for each variant allele when compared with the wild-type: CTLA4: A49G [rs231775; adjusted HR (aHR), 1.32 (1.1–1.6); P = 0.01] and XRCC1: Arg339Gln [rs25487; aHR, 1.28 (1.05–1.57); P = 0.02]. Both of these sequence variants had significant results in the opposite direction as prior published literature. Two DFS associations were of borderline significance in the same direction as prior literature: ERCC2: Lys751Gln [rs13181; aHR, 0.80 (0.6–1.0); P = 0.05] and TP53: Arg72Pro [rs1042522; aHR, 1.28 (1.0–1.6); P = 0.03], comparing number of variant alleles with reference of zero variants. Conclusions: None of the prognostic sequence variants previously published was validated for OS in our patients with early-stage radiation-treated head and neck cancer, though rs1381and rs1042522 had borderline significant association with DFS. Clin Cancer Res; 18(1); 196–206. ©2011 AACR.
1173 A NEW DOUBLE-EFFECT THERAPEUTIC STRATEGY USING A HISTONE DEACETYLASE INHIBITOR FOR HCV-ASSOCIATED HEPATOCELLULAR CARCINOMA
Authors: A. Genka, I. Satoh, S. Fukuda, S. Nagami, T. Muramatsu, Y. Saito, K. Sugiyama, H. Saito
Journal: Journal of Hepatology (2013)
Working as a praktikant in Sweden.
Authors: I C Hunter
Journal: BMJ (1980)

Like most medical students who spend their elective abroad, I shall always look back on mine with pleasure as I remember happy times enjoyed with new friends. I am also grateful for the opportunity it provided to get to know another country and its people. I spent the summer months working on my elective project with a Swedish drug company in a Stockholm suburb. I did this under the praktikant system, which allows science and technology students to spend their vacation working for a commercial firm and applying their know ledge and skills to the practical problems of running their own re search project. The praktikant usually joins a team and works under the super vision of the team leader, but he has a clearly defined research object ive for which he alone is responsible. He has to justify his methods and use of resources to the team leader, who acts as a scientific devil's advocate; but if the system works properly the leader should not use his control of the purse strings to dictate policy, nor should he assume the role of nursemaid when minor difficulties arise. The aim is that the praktikant should learn to accept responsibility for his own work and ideas. Thus the gap between student days and work is bridged in much the same way that clerkships and final-year locum jobs introduce the medical student to clinical responsibilities. The relationship between academic research and the pharmaceutical industry is closer in Sweden than in most other countries. In the commercial pharmacology department where I worked there were two senior researchers who were honorary associate professors at the University of Stockholm, and two others were recognised teachers. The company farmed out drug development projects to several university departments, and encouraged their co-operation on joint projects. Visits to our department by clinical and academic researchers were frequent and welcome.
Learning from the Russians
Authors: Belinda Hirsh
Journal: BMJ (2006)

L iz sneezed again and Alexandr's worried countenance became almost panicky. He summoned his secretary into the office who, in response to a few barked commands, adopted the same anxious look and hurriedly ushered Liz out of the room. It was our first full day in Russia and we did not want to appear rude or lacking in diplomacy, but we were worried by the apparent abduction of our colleague. The interpreter laughed and explained to us that Liz had been taken downstairs to the “salt cave” for treatment of her cold.

We had been sent from the United Kingdom to conduct a review of the Podmoskovny Lyceum, a charity-funded boarding school near Moscow. The lyceum provides top quality care, education, and accommodation free of charge for a specially selected group of children who come from disadvantaged backgrounds, have been victims of terrorism, have lived in areas of conflict, or whose parents serve in the Russian Border Guards in remote corners of the country. The …
Iloprost-induced thrombocytopenia: a case proven by rechallenge
Authors: A.B. Taegtmeyer, C. Zettler, M. Siegemund, D.A. Tsakiris, A.E. Rätz Bravo, H. Pargger, S. Kraehenbuehl, M. Haschke
Journal: European Respiratory Journal (2010)

were due to the effects of brachytherapy and not to the use of metallic clips or EBRT.In conclusion, although surgery remains the first choice to treat ROLC, a considerable number of patients are inoperable.EBRT is an alternative, but is hampered since the ROLC is effectively invisible.We report that the use of metallic clips placed during bronchoscopy can make ROLC visible for the radiation oncologist.The clips appear to be safe, well tolerated and removable in inoperable patients with ROLC who are candidates for EBRT.In the future, this technique could facilitate EBRT or even stereotactical beam radiotherapy in patients with ROLC.Prospective studies further investigating this technique are warranted.
Pulmonary Alveolar Proteinosis
Authors: David W. Cugell
Journal: JAMA (1975)

The pulmonary alveoli are lined with a highly surface-active lipid layer (predominantly phospholipid) that is essential for maintenance of normal alveolar architecture. Too little of this surface-active layer (known as surfactant) results in alveolar collapse and atelectasis. Too much surfactant may be the basis for the unusual disease, pulmonary alveolar proteinosis. In this disease, large amounts of lipidprotein material accumulate in the alveoli, lung volumes are diminished, gas transfer is impaired, and progressive pulmonary insufficiency results. Although pulmonary alveolar proteinosis is usually chronic and progressive, spontaneous remissions have occurred.<sup>1</sup> As noted by Jenkins et al on p 74 of this issue, pulmonary symptoms and an abnormal chest x-ray film are usually present for some years before a definite diagnosis, usually by lung biopsy, is established. Two types of treatment have been used: inhalation of mucolytic or proteolytic aerosols and lung lavage under general anesthesia. When there is progression of
PLATELET TRANSFUSIONS AND THE PATHOGENESIS OF IDIOPATHIC THROMBOCYTOPENIC PURPURA
Authors: Charles C. Sprague
Journal: JAMA (1952)

Interest in thrombocytopenic purpura has recently been stimulated by the demonstration that a circulating thrombocytopenic factor, presumably an antibody, is frequently involved in the pathogenesis of idiopathic thrombocytopenic purpura,1and by the suggestion that platelet transfusions may occasionally provide temporary relief from hemorrhagic manifestations in patients with low platelet levels caused by bone marrow depression.2During the past year, additional evidence has been obtained to indicate the importance of immunologic antiplatelet factors in the production of idiopathic thrombocytopenic purpura. It is the purpose of this paper to review that evidence, to relate it to previous ideas of pathogenesis, and to discuss the possible therapeutic application of platelet transfusions.  PATHOGENESIS OF IDIOPATHIC THROMBOCYTOPENIC PURPURA  The diminished number of platelets in idiopathic thrombocytopenic purpura has been attributed either to a decrease in their production or to an increased rate of destruction. Frank3was the first investigator to champion the