tbuckley/cabot-search huggingface dataset:
Enhancing Hospital Surge Capacity for Mass Casualty Events
Authors: Kobi Peleg
Journal: JAMA (2009)

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A novel “patient-like” model of cholangiocarcinoma progression based on bile duct inoculation of tumorigenic rat cholangiocyte cell lines
Authors: Alphonse E. Sirica, Zichen Zhang, Guan‐Hua Lai, Toru Asano, Xue‐Ning Shen, Deanna J. Ward, Arvind Mahatme, Jennifer L. DeWitt
Journal: Hepatology (2007)

Intrahepatic cholangiocarcinoma typically presents in an advanced stage in which treatment options are limited. In an effort to recapitulate key biological and clinical features of the progressive disease, we established a novel rat model based on bile duct inoculation of rat cholangiocyte cell lines in different stages of tumor progression. Our BDEneu cell line, which is highly tumorigenic, originated from an immortalized rat cholangiocyte cell line (BDE1 cells) that was stably transfected to constitutively overexpress mutationally activated rat neu oncogene. Our less aggressive tumorigenic BDEsp cholangiocyte cell line was derived from the spontaneous in vitro neoplastic transformation of the same parent BDE1 cell line. Unlike BDEneu cells, BDEsp cells expressed wild-type c-neu and exhibited in vitro growth rates intermediate between those of BDEneu and BDE1 cholangiocytes. Cyclooxygenase-2 and activated Akt were significantly overexpressed in BDEsp cells over those of BDE1 cells, and at higher levels than those expressed in BDEneu cells. Only BDEneu cells overexpressed activated p185neu, which was associated with a significant increase in phospho-p44/42 mitogen-activated protein kinase (MAPK). Mucin 1 (MUC1) messenger RNA (mRNA), an indicator of cholangiocarcinoma cell progression, was also significantly overexpressed in BDEneu cells over that of BDEsp cells. BDEneu cells inoculated into the bile duct of isogenic rats resulted over a 21- to 26-day period in rapid exponential cholangiocarcinoma tumor growth within liver, paralleled by increases in bile duct obstruction and gross peritoneal metastases. Under comparable conditions, BDEsp cells yielded only small nonmetastatic intrahepatic cholangiocarcinomas without bile duct obstruction. Conclusions: A novel model of cholangiocarcinoma progression mimicking progressive development of the advanced human disease has been established, which may serve as a powerful preclinical platform to study cholangiocarcinoma progression and for rapidly testing treatment approaches. (HEPATOLOGY 2008.)
Cerebral Hemodynamics, Blood Gases, and Electrolytes during Breath-Holding and the Valsalva Maneuver
Authors: JOHN S. MEYER, FUMIO GOTOH, YASUYUKI TAKAGI, RYOJI KAKIMI
Journal: Circulation (1966)

Continuous recordings of arterial and internal jugular blood oxygen tension, oxygen saturation, carbon dioxide tension, pH, sodium and potassium, together with PECO 2 , blood pressure, and electroencephalogram were obtained to compare the effects of inspiratory and expiratory breath-holding and the Valsalva maneuver on the cerebral circulation and cerebral oxygen availability in man. During the interval of tolerated breath-holding for 69 seconds or less, jugular venous oxygen tension was increased owing to increased cerebral blood flow resulting from an increase of arterial carbon dioxide tension. There was a statistically significant correlation between changes in JPO 2 and PaCO 2 , which proved to be more or less linear for both increases and decreases of PaCO 2 4 mm. above and below control levels. No threshold was found for changes in PaCO 2 altering effective cerebral perfusion and cerebral venous PO 2 , extremely small changes in PaCO 2 (less than 1 mm. Hg) altered cerebral oxygen availability within 10 to 20 seconds. During the Valsalva maneuver a consistent reduction of jugular oxygen tension was found associated with the sudden fall in arterial blood pressure and reduction of arterial carbon dioxide tension. The rapid changes in cerebral hemodynamics and cerebral oxygen availability during the procedure are briefly discussed.
Leukocytoclastic Vasculitis Associated With Positive HTLV-III Serological Findings
Authors: Anvarali M. Velji
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The Henoch-Schönlein type of vasculitis is one acute variety of leukocytoclastic vasculitis that manifests as "palpable purpura" and is frequently associated with systemic manifestations.<sup>1</sup>To our knowledge it has been seen in one previous homosexual male patient who had no clinical or serological manifestations of acute acquired immunodeficiency syndrome or its variants.<sup>2</sup>I report here the case of a homosexual man with Henoch-Schönlein purpura and positive human T-cell lymphotropic virus type III serological findings with massive gastrointestinal tract hemorrhage and disseminated intravascular coagulopathy (DIC). The adverse outcome was atypical of the general course seen in this disease, as most patients have resolution and recurrence with ultimate spontaneous resolution. <h3>Report of a Case.—</h3> A 43-year-old homosexual male patient was admitted to the hospital for lower-extremity skin lesions, joint pains, swollen feet, severe abdominal pain, hematuria, and bloody diarrhea. He had had hepatitis A virus, hepatitis B
PROGNOSTIC VALUE OF CARDIOPULMONARY EXERCISE TESTING IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Hidekazu Tsuneoka, Akira Koike, Osamu Nagayama, Koji Sakurada, Hitoshi Sawada, Kazutaka Aonuma, Tadanori Aizawa
Journal: Journal of the American College of Cardiology (2011)
Abstract 2823: TAK-441, a novel investigational small molecule hedgehog pathway inhibitor for use in cancer therapy
Authors: Hideaki Tojo, Sachio Shibata, Yoshihiko Satoh, Mihoko Kawamura, Masakazu Inazuka, Hiroko Yamakawa, Masahide Kashiwagi, Maki Miyamoto, Shigeru Kondo, Tomohiro Oohashi, Yuya Oguro, Satoshi Sasaki
Journal: Cancer Research (2011)

Abstract Dysregulation of hedgehog (Hh) signal, which is caused by Hh-ligand overexpression or patched1 (Ptch1) mutation, has been found to play an important role in tumorigenesis. TAK-441 is a potent and selective smoothened (Smo) antagonist that blocks Hh signaling. In the Gli-responsive promoter-luciferase (Gli-luc) reporter assay in NIH3T3/Gli-luc cells, TAK-441 inhibited Gli transcriptional activity with an IC50 of 4.4 nM. TAK-441 also inhibited expression of human Gli1 messenger mRNA with an IC50 of 1.9 nM in MRC5 human embryonic fibroblasts. In addition, TAK-441 inhibited binding of cyclopamine, a plant-derived well-known Smo inhibitor, to human Smo on 293T cells overexpressing human Smo with an IC50 of 8.6 nM. These data suggest that TAK-441 inhibits the Hh signaling pathway through its binding to Smo. Oral administration of TAK-441 (0.5, 1, 5, 25 mg/kg QD) in mice bearing a Ptch1 (+/-), p53(−/-) medulloblastoma allograft resulted in dose-dependent antitumor activity with concomitant reduction of Gli1 mRNA expression in the tumors. Complete remissions were observed in the 25 mg/kg QD dose cohort after two consecutive weeks of treatment. Significant (p≤0.025 by one-tailed Williams test) antitumor activity was also detected in sonic hedgehog expressing human primary pancreatic and ovarian cancer xenografts when dosed at 10 and 25 mg/kg QD for two weeks, and in a colon cancer xenograft when dosed at 6.25 and 25 mg/kg BID for three weeks. In these models, the expression of tumor-associated mouse stromal Gli1 mRNA was markedly decreased following TAK-441 treatment, suggesting that Hh signaling in these tumors was driven in a paracrine mode of action. The combination of TAK-441 and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), demonstrated significantly better antitumor activity than either agent alone in human primary pancreatic cancer xenograft models (p≤0.05 by Students’ t-test). In addition, delayed tumor re-growth was observed in the TAK-441/rapamycin combination treatment group compared with the rapamycin single-agent treatment group after terminating treatment. As a result of these preclinical studies, TAK-441 has recently entered Phase I clinical studies in cancer patients. 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 2823. doi:10.1158/1538-7445.AM2011-2823
High-Dose Daunorubicin in Older Patients with Acute Myeloid Leukemia
Authors: Bob Löwenberg, Gert J. Ossenkoppele, Wim van Putten, Harry C. Schouten, Carlos Graux, Augustin Ferrant, Pieter Sonneveld, Johan Maertens, Mojca Jongen-Lavrencic, Marie von Lilienfeld-Toal, Bart J. Biemond, Edo Vellenga, Marinus van Marwijk Kooy, Leo F. Verdonck, Joachim Beck, Hartmut Döhner, Alois Gratwohl, Thomas Pabst, Gregor Verhoef
Journal: New England Journal of Medicine (2009)

A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area.Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age (median, 67) were randomly assigned to receive cytarabine, at a dose of 200 mg per square meter by continuous infusion for 7 days, plus daunorubicin for 3 days, either at the conventional dose of 45 mg per square meter (411 patients) or at an escalated dose of 90 mg per square meter (402 patients); this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter every 12 hours [DOSAGE ERROR CORRECTED] for 6 days. The primary end point was event-free survival.The complete remission rates were 64% in the group that received the escalated dose of daunorubicin and 54% in the group that received the conventional dose (P=0.002); the rates of remission after the first cycle of induction treatment were 52% and 35%, respectively (P<0.001). There was no significant difference between the two groups in the incidence of hematologic toxic effects, 30-day mortality (11% and 12% in the two groups, respectively), or the incidence of moderate, severe, or life-threatening adverse events (P=0.08). Survival end points in the two groups did not differ significantly overall, but patients in the escalated-treatment group who were 60 to 65 years of age, as compared with the patients in the same age group who received the conventional dose, had higher rates of complete remission (73% vs. 51%), event-free survival (29% vs. 14%), and overall survival (38% vs. 23%).In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional dose, without additional toxic effects. (Current Controlled Trials number, ISRCTN77039377; and Netherlands National Trial Register number, NTR212.)
Reply to the Letters to the Editor from Greene et al.
Authors: Gil Mor, Peter E. Schwartz, Herbert Yu
Journal: Clinical Cancer Research (2008)

In Response : Concerns have been raised from some investigators about the positive predictive value (PPV) described in our recent publication, “Diagnostic markers for the early detection of ovarian cancer,” and an erratum table published later ([1][1], [2][2]). An additional concern is the
Book Review Psychoanalysis and Narrative Medicine (SUNY Series in Psychoanalysis and Culture.) Edited by Peter L. Rudnytsky and Rita Charon. 308 pp. Albany, State University of New York Press, 2008. $89.50 (cloth); $29.95 (paper). 978-0-7914-7351-1 (cloth); 978-0-7914-7352-8 (paper).
Authors: Robin Lydenberg
Journal: New England Journal of Medicine (2008)
Assessment of Portal Vein Invasion by Bile Duct Cancer Using Intraductal Ultrasonography
Authors: K. Tamada, K. Ido, N. Ueno, M. Ichiyama, T. Tomiyama, T. Nishizono, S. Wada, T. Noda, S. Tano, T. Aizawa, T. Ueno, K. Kimura
Journal: Endoscopy (1995)

Background and Study Aims: We recently reported on the contribution of intraductal ultrasonography (IDUS) to the regional staging of bile duct cancer, and we present here the first detailed study of the value of IDUS in assessing the portal vein invasion by bile duct cancer.
Influenza A virus enhances <i>Staphylococcus aureus</i>‐induced basophil histamine release in normal individuals and patients with intrinsic asthma
Authors: P. Clemensten, C. B. Jensen, J. O. Jarløv, C. Hannoun, M. Søborg, S. Norn
Journal: Allergy (1989)

Influenza A virus was found to enhance Staphylococcus aureus‐ histamine release in human leukocyte suspensions, but did not per se release histamine. This potentiating effect was found to be similar in cells from normal individuals and from patients with intrinsic asthma. The enhancement of mediator release could be due to viral neuraminidase on the surface of the virus, since a similar potentiating effect was caused by a purified neuraminidase preparation obtained from Vibrio cholerae , and the effect of virus as well as of the purified neuraminidase was completely abolished by a potent neuraminidase inhibitor. The potentiating effect of virus on bacteria‐induced mediator release might be of importance for the conversion from latent to manifest asthma in upper respiratory tract infections.
Woman is sentenced to 20 years in prison for feticide after death of baby
Authors: O. Dyer
Journal: BMJ (2015)

<h3>Abstract</h3> Humans have an extraordinary ability to interact and cooperate with others, which plays a pivotal role in societies at large. Despite its potential social and evolutionary significance, research on finding the neural correlates of collaboration has been limited partly due to restrictions on simultaneous neuroimaging of more than one participant (a.k.a. hyperscanning). A series of works now exists that used dyadic fMRI hyperscanning to examine the interaction between two participants. However, to our knowledge, no study to date has aimed at revealing the neural correlates of social interactions using a 3-person (or triadic) fMRI hyperscanning paradigm. Here, for the first time, we simultaneously measured the blood-oxygenation-level-dependent (BOLD) signal of triads (m=12 triads; n=36 participants), while they engaged in a joint drawing task based on the social game of Pictionary<sup>®</sup>. General linear model (GLM) analysis revealed increased activation in the brain regions previously linked with the theory of mind (ToM) during the collaborative phase compared to the independent phase of the task. Furthermore, using intersubject brain synchronization (IBS) analysis, we revealed increased synchrony of the right temporo-parietal junction (R TPJ) during the collaborative phase. The increased synchrony in the R TPJ was observed to be positively associated with the overall team performance on the task. In sum, our novel paradigm revealed a vital role of the R TPJ among other ToM regions during a triadic collaborative drawing task.
The value of life
Authors: L. Farrell
Journal: BMJ (1998)

A few weeks ago I visited W B Yeats's grave and sat awhile in thought; no towers of adamant nor rings of steel, just a simple stone monument with the words, “Cast a cold eye/ On life, on death/Horseman pass by.”

A few hours later and a few miles south, I was in a bar on the Atlantic coast, drinking a pint of the blackest porter, eating crab claws fresh from the sea and soaking in garlic butter, and hammering away at my guitar in an impromptu folk music session. Pausing to check that the kids were still alive …
Beyond rhetoric: we need a strategy for patient involvement in the health service
Authors: S. Thornton
Journal: BMJ (2014)

The UK government is heavy on the hyperbole of empowering patients but lacks a robust strategy, says Sarah Thornton 

Respect for a patient’s individual autonomy is an accepted principle in modern medicine. In the past half century, the concept of autonomy has usurped medical paternalism in almost all of its forms and has aspired to promote patients from passive recipients of care to partners in planning their own treatment.1 Now the concept has extended beyond individual autonomy to an expectation of empowerment at the population level.

The notion of patient empowerment is reflected in the development of regulation and guidance, and phrases such as “patient led care,” “putting patients at the heart of the NHS,” and “shared treatment decision making” abound. Since the NHS Plan in 2000, the UK government has promised to “encourage the involvement of citizens in redesigning the health service from the patients’ point of view.”2

Despite the strong rhetoric, however, there has been no consistent strategy for involving patients. The approach to enabling patients and the general public to have more say about how services are planned and …
Survival in families with hereditary protein C deficiency, 1820 to 1993
Authors: C F Allaart, F R Rosendaal, W M P Noteboom, J P Vandenbroucke, E Briet
Journal: BMJ (1995)

OBJECTIVES —To establish the survival of individuals heterozygous for hereditary protein C deficiency, who have an increased risk ofvenous thrombotic events, and to compare it with the survival of the general population. DESIGN —Retrospective study in pedigrees of23 families with hereditary protein C deficiency for period 1820 and 1993. SETTING —23 completed family trees of 24 probandsfrom various parts of the Netherlands with symptoms of protein C deficiency. SUBJECTS —All 736 members of the 23 families with a50% or 100% probability of being (or having been) heterozygous for the genetic defect on the basis of DNA analysis or their place inthe pedigrees, following mendelian rules. MAIN OUTCOME MEASURES —Observed mortality compared with the mortality of thegeneral Dutch population; the standardised mortality ratio was calculated by dividing the observed mortality by the expected mortality. RESULTS —No excess mortality was found in the 206 proved heterozygous individuals and "obligatory transmitters" (those who havedefinitely passed on the deficiency) (standardised mortality ratio 0.95 (95% confidence interval 0.5 to 1.2)) or in the 530 familymembers with a 50% genetic probability of heterozygosity (1.10 (0.9 to 1.3)). CONCLUSION —Heterozygous individuals withhereditary protein C deficiency type I have normal survival compared with the general population. Prophylactic anticoagulant treatmentmay prevent thrombotic events in heterozygous individuals but may not be expected to improve their survival.
Blood cholesterol measurement in young adults
Authors: D. M. Lane
Journal: JAMA (1993)

In Reply.  —We agree with Dr Tobert that the small number of deaths in the EXCEL trial precludes firm conclusions about the impact of lovastatin on mortality, but we take little comfort from his comments on cause of death. The fact is that a higher proportion of lovastatin-treated patients died. It is disturbing that this large study funded by Tobert's employer had only 1 year of follow-up, and that it is the only randomized trial of this drug with published disease event outcomes. This leaves us in the position of hoping that other trials will show that death rates decrease and keeping our fingers crossed in the meantime. Such uncertainty about a new class of drugs that is already widely used seems unacceptable, raising questions about the use of surrogate end points by Food and Drug Administration advisory panels to recommend long-term drug treatment for healthy people.  As to Dr
Tropical splenomegaly, sickle cell trait, and P. falciparum infection.
Authors: M Janosi
Journal: BMJ (1972)

colleagues they should estimate the require- ments for the next 12 months, and based on this assessment and the antici- pated fractionation yields collect the neces- sary raw material within their region for the patients for whom they are directly responsible.This done, the ball is firmly in the court of the central fractionation units to make the necessary capacity available to pre- pare and deliver high quality products to the regional transfusion centres in the quantity requested.This principle should hold for all plasma fractionation products and would thus throw the burden of responsibility for patient care where it belongs-to the regional transfusion centres.-Weare, etc.,
Clinical features and natural course of Behçet’s disease in 661 cases: a multicentre study
Authors: E. Alpsoy, L. Donmez, M. Onder, S. Gunasti, A. Usta, Y. Karincaoglu, B. Kandi, S. Buyukkara, O. Keseroglu, S. Uzun, U. Tursen, M. Seyhan, A. Akman
Journal: British Journal of Dermatology (2007)

Behçet's disease (BD) is a systemic inflammatory disease with unpredictable exacerbations and remissions. The natural course of BD is not fully known.We aimed retrospectively to determine the occurrence of the symptoms in chronological order. We also evaluated the influence of the treatment and follow-up on the clinical severity and tried to identify the factors determining severe organ involvement.Six hundred and sixty-one patients were involved in this multicentre study. The symptoms of the disease were recorded retrospectively in the time order of the manifestations in each patient.Oral ulcers were the most common manifestation (100%), followed by genital ulcers (85.3%), papulopustular lesions (55.4%), erythema nodosum (44.2%), skin pathergy reaction (37.8%), and articular (33.4%) and ocular involvement (29.2%). Oral ulcers were the most common onset manifestation (88.7%). The mean +/- SD duration between the onset symptom and the fulfilment of diagnostic criteria was calculated to be 4.3 +/- 5.7 years. The clinical severity score was significantly increased in the noncompliant treatment group compared with the compliant group with the passage of time (P < 0.001). The frequency of ocular involvement and genital ulcers was significantly higher in patients whose disease onset was at < 40 years. Genital ulcers, ocular involvement, papulopustular lesions, thrombophlebitis and skin pathergy reaction were found to be significantly more frequent in males.Mucocutaneous lesions are the hallmarks of the disease, and especially oral ulcers precede other manifestations. The increase in clinical severity score is more pronounced in patients without regular treatment and follow-up. Male sex and a younger age at onset are associated with more severe disease.
Complete Periprostatic Anatomy Preservation During Robot-Assisted Laparoscopic Radical Prostatectomy (RALP): The New Pubovesical Complex-Sparing Technique
Authors: Anastasios D. Asimakopoulos, Filippo Annino, Alejandro D'Orazio, Clovis Fraga T. Pereira, Camille Mugnier, Jean-Luc Hoepffner, Thierry Piechaud, Richard Gaston
Journal: European Urology (2010)