tbuckley/cabot-search huggingface dataset:
Catecholaminergic Polymorphic Ventricular Tachycardia in Children
Authors: Antoine Leenhardt, Vincent Lucet, Isabelle Denjoy, Francis Grau, Dien Do Ngoc, Philippe Coumel
Journal: Circulation (1995)

Background Primary ventricular tachyarrhythmias are rarely seen in children. Among them, catecholaminergic polymorphic ventricular tachycardia has a poor spontaneous outcome. Its diagnosis is often delayed after the first symptoms, which is unacceptable because treatment with the appropriate β-blocker prevents sudden death. Methods and Results We observed 21 children (mean±SD age, 9.9±4 years) at the time of the diagnosis who had no structural heart disease and a normal QT interval on routine ECG. They were referred for stress- or emotion-induced syncope related to ventricular polymorphic tachyarrhythmias. The arrhythmia, consisting of isolated polymorphic ventricular extrasystoles followed by salvoes of bidirectional and polymorphic tachycardia susceptible to degeneration into ventricular fibrillation, was reproducibly induced by any form of increasing adrenergic stimulation. There was a familial history of syncope or sudden death in 30% of our patients. On receiving therapy with the appropriate β-blocker, the patients’ symptoms and polymorphic tachyarrhythmias disappeared. During a mean follow-up period of 7 years, three syncopal events and two sudden deaths occurred, probably due to treatment interruption. Conclusions The entity of adrenergic-dependent, potentially lethal tachyarrhythmia with no structural heart disease deserves to be individualized. It may form a variant of the congenital long QT syndrome in which the ECG marker is lacking; this primary ventricular arrhythmia must be looked for in a pediatric patient with stress- or emotion-induced syncope because only β-blocking therapy can prevent sudden death and therefore must be given for the patient’s lifetime.
Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12.
Authors: Y G Yang, B R Dey, J J Sergio, D A Pearson, M Sykes
Journal: Journal of Clinical Investigation (1998)

We have demonstrated that a single injection of interleukin (IL)-12 on the day of bone marrow transplantation (BMT) inhibits acute graft-versus-host disease (GVHD) in mice. This effect of IL-12 can be diminished by anti-interferon (IFN)-gamma mAb. To determine the mechanism by which IFN-gamma affects IL-12-mediated GVHD protection, we have compared the effect of IL-12 on GVHD in C57BL/6 wild-type (WT) or IFN-gamma gene knockout (GKO) recipients of fully major histocompatibility complex plus minor antigen-mismatched allogeneic BMT from WT or GKO BALB/c mice. Lethal acute GVHD was readily induced in the absence of IFN-gamma. IL-12 inhibited GVHD mortality to a similar extent in WT and GKO recipients of WT allogeneic BMT. However, neither WT nor GKO recipients were protected by IL-12 from GVHD induced by GKO allogeneic BMT. Moreover, the effective inhibition of host-reactive donor T cell activation and expansion that is associated with IL-12-mediated GVHD protection was dependent on the ability of BALB/c donors to produce IFN-gamma. These results demonstrate that (a) acute GVHD can be induced in the absence of IFN-gamma, (b) host IFN-gamma does not play a critical role in IL-12-induced GVHD protection, and (c) the protective effect of IL-12 against GVHD is dependent on the ability of the donor to produce IFN-gamma.
THYROIDECTOMY: ITS RELATION TO THE CURE OF THYROTOXICOSIS
Authors: H. M. RICHTER
Journal: JAMA (1927)

Aside from all question of the exciting cause, the immediate source of the clinical syndrome called exophthalmic goiter lies entirely within the thyroid gland. Tomorrow we may be able to reach the activating agent; today we must reach the activated gland itself. Its removal is incompatible with the continued existence of the disease in its various forms.  Nowhere in medicine is more inexplicable sophistry displayed than in the discussion of this subject. To state that such a percentage of patients are cured by thyroidectomy evidences a total failure to grasp the relation of the thyroid gland to the disease and of thyroidectomy to its cure.  A prophylactic inoculation that fails to prevent smallpox does not lead to any discussion of the preventive value of vaccinia. The presence of smallpox is evidence that vaccinia was not produced, whatever may have been the local reaction following the attempted vaccination. The failure of
Prevention of atrial fibrillation following cardiac surgery: Basis for a novel therapeutic strategy based on non-hypoxic myocardial preconditioning
Authors: Ramón Rodrigo, Mauricio Cereceda, Rodrigo Castillo, René Asenjo, Jaime Zamorano, Julia Araya, Rodrigo Castillo-Koch, Juan Espinoza, Ernesto Larraín
Journal: Pharmacology & Therapeutics (2008)
Classical Hodgkin's lymphoma arising in different host's conditions: Pathobiology parameters, therapeutic options, and outcome
Authors: Antonino Carbone, Michele Spina, Annunziata Gloghini, Umberto Tirelli
Journal: American Journal of Hematology (2010)

Abstract Epidemiologic and molecular findings suggest that classical Hodgkin's lymphoma (CHL) is not a single disease but consists of more than one entity and may occur in different clinical settings. This review analyzes similarities and disparities among CHL entities arising in different host's conditions with respect to pathobiology parameters, therapeutic options, and outcome. For the purpose of this analysis, CHL entities have been subdivided according to the immune status of the host. In nonimmunosuppressed hosts, according to the age, CHL include pediatric, adult, and elderly forms, whereas, in immunosuppressed hosts, according to the type of immunosuppression, CHL include human immunodeficiency virus (HIV)‐associated, iatrogenic, and post‐transplant types. CHL entities in different settings are similar in morphology of neoplastic cells, expression of activation markers, and aberrations/activation of NFKB, JAK/STAT, and P13K/AKT pathways, but differ in the association with Epstein‐Barr virus (EBV) infection, persistent B‐cell phenotype, and cellular background composition. Large B‐cell lymphomas resembling CHL may also be observed in the same clinical settings. These lesions, however, do not fulfill the diagnostic criteria of CHL and clinically display a very aggressive behavior. In this article, current treatment options for the CHL entities, especially for elderly CHL and HIV‐associated CHL, are specifically reviewed. ABVD remains the gold standard both in nonimmunosuppressed or immunosuppressed hosts even if there are several data suggesting a possible improvement in outcome using the aggressive BEACOPP regimen in advanced stages. Refractory CHL, a clinical condition that may occur throughout the entire spectrum of CHL, is discussed separately. Am. J. Hematol., 2011. © 2010 Wiley‐Liss, Inc.
Myeloablative Hematopoietic Cell Transplantation for Acute Lymphoblastic Leukemia: Analysis of Graft Sources and Long-Term Outcome
Authors: Michael B. Tomblyn, Mukta Arora, K. Scott Baker, Bruce R. Blazar, Claudio G. Brunstein, Linda J. Burns, Todd E. DeFor, Kathryn E. Dusenbery, Dan S. Kaufman, John H. Kersey, Margaret L. MacMillan, Philip B. McGlave, Jeffrey S. Miller, Paul J. Orchard, Arne Slungaard, Marcie R. Tomblyn, Gregory M. Vercellotti, Michael R. Verneris, John E. Wagner, Daniel J. Weisdorf
Journal: Journal of Clinical Oncology (2009)

Analysis of hematopoietic cell transplantation (HCT) for high-risk or recurrent acute lymphoblastic leukemia (ALL) using different donor sources is confounded by variable conditioning and supportive care.We studied 623 consecutive ALL myeloablative HCT (1980 to 2005). Donors were autologous (n = 209), related (RD; n = 245), unrelated (URD; n = 100), and umbilical cord blood (UCB; n = 69).After median of 8.3 years of follow-up, 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 29% (95% CI, 26% to 32%), 26% (95% CI, 23% to 29%), and 43% (95% CI, 39% to 47%), respectively. Treatment-related mortality (TRM) at 2 years was 28% (95% CI, 25% to 31%). Mismatched URD sources yielded higher TRM (relative risk [RR], 2.2; P < .01) and lower OS (RR, 1.5; P = .05) than RD or UCB HCT. Autografting yielded significantly more relapse (68%; 95% CI, 59% to 77%; P < .01) and poorer LFS (14%; 95% CI, 10% to 18%; P = .01). HCT in first complete remission (CR1) yielded significantly better outcomes than later HCT. In a 1990 to 2005 allogeneic CR1/second complete response cohort, 5-year OS, LFS, and relapse rates were 41% (95% CI, 35% to 47%), 38% (95% CI, 32% to 44%), and 25% (95% CI, 19% to 31%), respectively; 2-year TRM was 34% (95% CI, 28% to 40%). With RD, well-matched URD and UCB sources, 5-year LFS was 40% (95% CI, 31% to 49%), 42% (95% CI, 14% to 70%), and 49% (95% CI, 34% to 64%), respectively, while relapse was 31% (95% CI, 22% to 40%), 17% (95% CI, 0% to 37%), and 27% (95% CI, 13% to 41%). Acute graft-versus-host disease was associated with fewer relapses. Since 1995, we noted progressive improvements in OS, LFS, and TRM.Allogeneic, but not autologous, HCT for ALL results in durable LFS. Importantly, HCT using UCB led to similar outcomes as either RD or well-matched URD. HCT in early remission can best exploit the potent antileukemic efficacy of allografting from UCB, RD, or URD sources.
A New Model for Prediction of Drug Distribution in Tumor and Normal Tissues: Pharmacokinetics of Temozolomide in Glioma Patients
Authors: Lula Rosso, Cathryn S. Brock, James M. Gallo, Azeem Saleem, Patricia M. Price, Federico E. Turkheimer, Eric O. Aboagye
Journal: Cancer Research (2008)

Abstract Difficulties in direct measurement of drug concentrations in human tissues have hampered the understanding of drug accumulation in tumors and normal tissues. We propose a new system analysis modeling approach to characterize drug distribution in tissues based on human positron emission tomography (PET) data. The PET system analysis method was applied to temozolomide, an important alkylating agent used in the treatment of brain tumors, as part of standard temozolomide treatment regimens in patients. The system analysis technique, embodied in the convolution integral, generated an impulse response function that, when convolved with temozolomide plasma concentration input functions, yielded predicted normal brain and brain tumor temozolomide concentration profiles for different temozolomide dosing regimens (75–200 mg/m2/d). Predicted peak concentrations of temozolomide ranged from 2.9 to 6.7 μg/mL in human glioma tumors and from 1.8 to 3.7 μg/mL in normal brain, with the total drug exposure, as indicated by the tissue/plasma area under the curve ratio, being about 1.3 in tumor compared with 0.9 in normal brain. The higher temozolomide exposures in brain tumor relative to normal brain were attributed to breakdown of the blood-brain barrier and possibly secondary to increased intratumoral angiogenesis. Overall, the method is considered a robust tool to analyze and predict tissue drug concentrations to help select the most rational dosing schedules. [Cancer Res 2009;69(1):120–7]
The effect of salt water on alveolar epithelial barrier function.
Authors: H G Folkesson, F Kheradmand, M A Matthay
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The effect of hyperosmolar fluid aspiration (seawater) on lung fluid balance has not been well studied. Therefore, the effect of this clinically relevant form of acute lung injury on the alveolar epithelial and lung endothelial barriers was examined in ventilated, anesthetized rabbits. Seawater (4 ml/kg body weight, 881 +/- 29 mOsm/kg) with 3 microCi of 125I-albumin was instilled into the lower trachea of ventilated, anesthetized rabbits. Osmotic equilibration with plasma was completed within the first 5 min after seawater instillation. In parallel with the osmotic equilibration of the seawater in the air spaces, there was a 3-fold dilution of the alveolar protein tracer 125I-albumin, indicating an initial large (300%) increase in alveolar fluid volume. There was a marked decline in arterial oxygenation at the same time that the alveolar fluid volume markedly increased. The initial dilution of the alveolar protein tracer was followed by a progressive increase in the alveolar protein tracer concentration that continued until 6 h after seawater instillation. As the alveolar protein tracer concentrated, arterial oxygenation improved, indicting net alveolar liquid clearance. There was only a mild increase in the epithelial and endothelial permeability to protein within the first 2 h after seawater instillation. Thus, a large osmotically induced increase in alveolar fluid volume with severe pulmonary edema did not cause sustained injury to the endothelial or epithelial barriers of the lung. In fact, normal alveolar liquid clearance occurred, indicating the resistance of the epithelial barrier to hyperosmolar injury as well as its capacity to rapidly reabsorb excess alveolar fluid.
Surgical embolectomy is underused
Authors: E. W. K. Peng, J. Simpson, L. Thirugnanasothy, P. Kesteven, J. H. Dark
Journal: BMJ (2013)

Pulmonary embolism remains a major healthcare burden and some patients still die from this preventable disease, perhaps because of limited knowledge about available treatments for massive pulmonary embolism.1

Systemic thrombolysis has been the mainstay for massive pulmonary embolism. Other options include transcatheter clot removal and locally directed thrombolysis, but their application is …
Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes
Authors: Sharat Srinivasula, Richard A. Lempicki, Joseph W. Adelsberger, Chiung-Yu Huang, Joshua Roark, Philip I. Lee, Adam Rupert, Randy Stevens, Irini Sereti, H. Clifford Lane, Michele Di Mascio, Joseph A. Kovacs
Journal: Blood (2011)
PDZK1: I. A major scaffolder in brush borders of proximal tubular cells11See Editorial by Moe, p. 1916.
Authors: Serge M. Gisler, Sandra Pribanic, Desa Bacic, Patrik Forrer, Andrea Gantenbein, Luc A. Sabourin, Akira Tsuji, Zhuo-Shen Zhao, Edward Manser, Jürg Biber, Heini Murer
Journal: Kidney International (2003)
Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice
Authors: Stephan Wueest, Reto A. Rapold, Desiree M. Schumann, Julia M. Rytka, Anita Schildknecht, Ori Nov, Alexander V. Chervonsky, Assaf Rudich, Eugen J. Schoenle, Marc Y. Donath, Daniel Konrad
Journal: Journal of Clinical Investigation (2009)

Adipose tissue inflammation is linked to the pathogenesis of insulin resistance. In addition to exerting death-promoting effects, the death receptor Fas (also known as CD95) can activate inflammatory pathways in several cell lines and tissues, although little is known about the metabolic consequence of Fas activation in adipose tissue. We therefore sought to investigate the contribution of Fas in adipocytes to obesity-associated metabolic dysregulation. Fas expression was markedly increased in the adipocytes of common genetic and diet-induced mouse models of obesity and insulin resistance, as well as in the adipose tissue of obese and type 2 diabetic patients. Mice with Fas deficiency either in all cells or specifically in adipocytes (the latter are referred to herein as AFasKO mice) were protected from deterioration of glucose homeostasis induced by high-fat diet (HFD). Adipocytes in AFasKO mice were more insulin sensitive than those in wild-type mice, and mRNA levels of proinflammatory factors were reduced in white adipose tissue. Moreover, AFasKO mice were protected against hepatic steatosis and were more insulin sensitive, both at the whole-body level and in the liver. Thus, Fas in adipocytes contributes to adipose tissue inflammation, hepatic steatosis, and insulin resistance induced by obesity and may constitute a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.
Rectal perforation due to benign stricture caused by rectal burns associated with hot coffee enemas
Authors: S. Kim, J. Cha, C. Lee, H. Shin, J. Park, K. Joo, J. Lee, J. Jeun, K. Lim, J. Lim, J. Choi
Journal: Endoscopy (2012)

A 27-year-old woman visited our hospital complaining of lower abdominal and anal pain, developed several minutes after a hot coffee enema to relieve constipation. Abdominopelvic computed tomography (CT) revealed marked wall thickening in the entire rectum and surrounding fluid collection that suggested severe necrotic mucosal change ([Fig. 1]). Sigmoidoscopy showed necrotic mucosal lesions with hemorrhage and exudates in the rectum ([Fig. 2]). She recovered with supportive treatment, and follow-up sigmoidoscopy showed benign stricture and ulcer scars ([Fig. 3]). On the 46th clinical day, the patient revisited the emergency department for terrible abdominal pain that had suddenly developed during straining and bowel movements. She was diagnosed with rectal perforation and peritonitis on the basis of CT scans. Laparoscopy revealed a 4-cm perforation of the upper rectum with fecal soilage ([Fig. 4]). Primary repair and temporary colostomy was performed. On the 130th clinical day, she was asymptomatic and sigmoidoscopy showed scarring with mild stricture ([Fig. 5]). Finally, she was discharged in satisfactory condition after a colostomy take-down procedure.
Lymphokine-activated killer cells. Analysis of progenitors and effectors.
Authors: J R Ortaldo, A Mason, R Overton
Journal: The Journal of Experimental Medicine (1986)

IL-2 has been examined for its ability to regulate lymphokine-activated killer (LAK) activity. IL-2 is a potent activator of cytolytic activity against a wide array of tumor cells, including those from fresh autologous and allogeneic tumors. Using subpopulations of lymphoid cells that were separated on Percoll density gradients, and subsequently purified by immunoadsorbance, studies were performed to examine the phenotypes of progenitor and effector cells of human LAK cells and to compare them with the phenotype of activated NK cells. From these studies, it was evident that several lymphoid subsets, including CD3+, CDw16- and CD3-, CDw16+ cells could mediate LAK lysis of fresh tumor cells. Our examination of the kinetics of activation revealed that CDw16+, NKH1+ (NK-active) cells were maximally activated by 1-2 d. In contrast, CD3+ cells appeared not to achieve maximal cytolytic activity against fresh and cultured tumor cells until days 2-3. Using limiting-dilution frequency analysis, we showed that a large percentage of cytolytically active progenitors was present among the CDw16+, NKH1+ cells. The progenitor and effector cell frequencies appear to be 10-50 times higher in these populations compared to CD3+ cells. In addition, the selective blockage by mAb to the CD3 determinant of the T cell receptor complex indicated that these two effector cell phenotypes relied on different receptors to mediate their cytotoxic activity against tumor cells. Therefore, the accumulated data suggest that there is not a single unique progenitor of LAK activity, but rather that multiple subsets of lymphocytes become cytotoxic in response to IL-2. However, the NK cell population forms the largest single component of LAK cell activity in human peripheral blood.
CNS Effects and Abuse Liability of Anabolic-Androgenic Steroids
Authors: S E Lukas
Journal: The Annual Review of Pharmacology and Toxicology (1996)

Anabolic-androgenic steroids (AAS) have become more widely used and abused not only by elite athletes, but by nonathletes as well. It appears that these drugs are being used for cosmetic purposes as well as for promoting aggressive behavior. However, AASs may also be used in combination with other drugs such as ethyl alcohol and cocaine--a practice that may contribute to the observed increase in aggressive behavior. As there are no reliable animal models of AAS self-administration, it has been difficult to characterize the abuse liability and physical dependence potential of this class of drugs. A better understanding of neuroactive steroids, improved methods for assessing AAS abuse, and a revised interpretation of drug-seeking behavior is needed to develop improved treatment strategies for this emerging health-related problem.
BioSTAR Evaluation STudy (BEST)
Authors: Michael J. Mullen, David Hildick-Smith, Joseph V. De Giovanni, Christopher Duke, W. Stewart Hillis, W. Lindsay Morrison, Christian Jux
Journal: Circulation (2006)

Background— The use of permanent synthetic implants to close atrial septal defects (ASD) and patent foramen ovale (PFO) has a number of limitations, including late complications and the limiting of transeptal access to the left heart should it be required for the later treatment of acquired heart disease. BioSTAR is a novel, bioabsorbable, atrial septal repair implant. This phase I pilot study evaluates the feasibility, safety, and effectiveness of BioSTAR for the first time in humans. Methods and Results— We conducted a prospective, open-label, multicenter clinical study in 58 patients aged 28 to 68 years who had a clinically significant ASD or PFO. Percutaneous shunt closure was undertaken with the BioSTAR septal repair implant. Successful device implantation was achieved in 57 (98%) of 58 patients. Closure at 30 days and 6 months, assessed by contrast transthoracic echocardiography, was 48 (92%) of 52 and 54 (96%) of 56, respectively. There was no evidence of a clinically significant response to the device. Transient atrial arrhythmia occurred in 5 patients after implantation. No major safety issues were observed. Conclusions— This study demonstrates the feasibility, safety, and effectiveness of BioSTAR for the closure of ASD and PFO in humans with a high rate of early and complete shunt closure. BioSTAR is a novel septal repair implant designed to provide biological closure of atrial-level defects using the patient’s natural healing response. Because 90% to 95% of the implant is absorbed and replaced with healthy native tissue, future access to the left atrium may be achieved.
Cholangiocarcinomas can originate from hepatocytes in mice
Authors: Biao Fan, Yann Malato, Diego F. Calvisi, Syed Naqvi, Nataliya Razumilava, Silvia Ribback, Gregory J. Gores, Frank Dombrowski, Matthias Evert, Xin Chen, Holger Willenbring
Journal: Journal of Clinical Investigation (2012)

Intrahepatic cholangiocarcinomas (ICCs) are primary liver tumors with a poor prognosis. The development of effective therapies has been hampered by a limited understanding of the biology of ICCs. Although ICCs exhibit heterogeneity in location, histology, and marker expression, they are currently thought to derive invariably from the cells lining the bile ducts, biliary epithelial cells (BECs), or liver progenitor cells (LPCs). Despite lack of experimental evidence establishing BECs or LPCs as the origin of ICCs, other liver cell types have not been considered. Here we show that ICCs can originate from fully differentiated hepatocytes. Using a mouse model of hepatocyte fate tracing, we found that activated NOTCH and AKT signaling cooperate to convert normal hepatocytes into biliary cells that act as precursors of rapidly progressing, lethal ICCs. Our findings suggest a previously overlooked mechanism of human ICC formation that may be targetable for anti-ICC therapy.
N‐terminal pro‐brain natriuretic peptide from fresh urine for the biochemical detection of heart failure and left ventricular dysfunction
Authors: Carsten G. Jungbauer, Stefan Buchner, Christoph Birner, Markus Resch, Norbert Heinicke, Kurt Debl, Monika Buesing, Daniela Biermeier, Gerd Schmitz, Günter Riegger, Andreas Luchner
Journal: European Journal of Heart Failure (2010)