tbuckley/cabot-search huggingface dataset:
Extramedullary disease and targeted therapies for hematological malignancies—is the association real?
Authors: P Raanani, O Shpilberg, I Ben-Bassat
Journal: Annals of Oncology (2006)

During the past years targeted therapies have gained a major role in the treatment of cancer patients, including those with hematological malignancies. Extramedullary involvement is a rare manifestation of acute and chronic leukemias and of multiple myeloma. Nevertheless, with the expanding use of targeted treatments there is an impression that the incidence of extramedullary relapses is increasing. We reviewed the reports on this phenomenon in patients treated with all-trans-retinoic acid and arsenic trioxide for acute promyelocytic leukemia, thalidomide and bortezomib for multiple myeloma and imatinib for chronic myeloid leukemia. The pathogenetic mechanisms suggested are: life prolongation by these treatments allowing for disease progression arising from dormant cells; poor penetration of the drugs to sanctuary sites like the central nervous system; the requirement of some of these drugs, especially thalidomide, for the marrow microenvironment to exert their action; and finally, a possible active role for some of the drugs, like all-trans-retinoic acid. Since the use of these targeted therapies is expanding we should be aware of this association.
Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults
Authors: Nor’azim Mohd Yunos, Rinaldo Bellomo, Colin Hegarty, David Story, Lisa Ho, Michael Bailey
Journal: JAMA (2012)

Administration of traditional chloride-liberal intravenous fluids may precipitate acute kidney injury (AKI).To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with AKI in critically ill patients.Prospective, open-label, sequential period pilot study of 760 patients admitted consecutively to the intensive care unit (ICU) during the control period (February 18 to August 17, 2008) compared with 773 patients admitted consecutively during the intervention period (February 18 to August 17, 2009) at a university-affiliated hospital in Melbourne, Australia.During the control period, patients received standard intravenous fluids. After a 6-month phase-out period (August 18, 2008, to February 17, 2009), any use of chloride-rich intravenous fluids (0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution) was restricted to attending specialist approval only during the intervention period; patients instead received a lactated solution (Hartmann solution), a balanced solution (Plasma-Lyte 148), and chloride-poor 20% albumin.The primary outcomes included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the risk, injury, failure, loss, end-stage (RIFLE) classification. Secondary post hoc analysis outcomes included the need for renal replacement therapy (RRT), length of stay in ICU and hospital, and survival. RESULTS Chloride administration decreased by 144 504 mmol (from 694 to 496 mmol/patient) from the control period to the intervention period. Comparing the control period with the intervention period, the mean serum creatinine level increase while in the ICU was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P <.001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P <.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge. CONCLUSION The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT.Clinicaltrials.gov Identifier: NCT00885404.
RAPID CHANGES IN THE O<sub>2</sub>TENSION OF CEREBRAL CORTEX DURING INDUCED CONVULSIONS
Authors: E. W. DAVIS, W. S. MCCULLOCH, E. ROSEMAN
Journal: American Journal of Psychiatry (1944)

A relative anoxia of the cerebral cortex occurs before, during and after convulsions induced electrically or by a variety of drugs. This relative anoxia is believed to be caused by increased cerebral metabolism.
Thrombin modulates phosphoinositide metabolism, cytosolic calcium, and impulse initiation in the heart.
Authors: S F Steinberg, R B Robinson, H B Lieberman, D M Stern, M R Rosen
Journal: Circulation Research (1991)

Thrombin stimulates phosphoinositide hydrolysis and increases cytosolic calcium in several types of cells. To determine whether thrombin exerts similar stimulatory actions in the heart and whether this mechanism is linked to changes in cardiac electrical activity, the effects of thrombin on several biochemical and electrophysiological parameters were examined. In neonatal rat ventricular myocyte cultures freed of fibroblast contamination by irradiation, thrombin rapidly induced the breakdown of phosphoinositides. Formation of inositol trisphosphate was detectable within 5 seconds and was followed by the sequential accumulation of inositol bisphosphate and inositol monophosphate. The effect of thrombin to stimulate phosphoinositide hydrolysis was inhibited by hirudin, but not by propranolol, prazosin, or pretreatment with pertussis toxin. The inositol phospholipid response was unassociated with changes in intracellular cAMP levels. To determine the electrophysiological effects of thrombin, we used microelectrode techniques to study canine Purkinje fibers. Thrombin increased the beating rate of fibers depolarized using barium, but not those at normal maximal diastolic potential. In addition, thrombin prolonged the action potential duration in fibers driven at a constant cycle length. This response was inhibited by hirudin and nisoldipine, but not by propranolol, prazosin, or pretreatment with pertussis toxin. Thrombin also augmented cesium-induced early afterdepolarizations. Using the fluorescent calcium indicator fura-2, we demonstrated that thrombin increased the beating rate, diastolic calcium, and peak systolic calcium of spontaneously contracting cultured ventricular myocytes. Cytosolic calcium also increased in both rat ventricular myocytes and canine Purkinje myocytes that were electrically driven at a constant basic cycle length, indicating that thrombin modulates cellular calcium metabolism independent of its actions to enhance automaticity. Taken together, these findings demonstrate several novel biological actions of thrombin in the mammalian heart that may be functionally related. The actions of thrombin to enhance automaticity and prolong repolarization may contribute to the electrical abnormalities observed in the setting of myocardial ischemia and infarction.
Surgical Complications Associated With Sentinel Lymph Node Dissection (SLND) Plus Axillary Lymph Node Dissection Compared With SLND Alone in the American College of Surgeons Oncology Group Trial Z0011
Authors: Anthony Lucci, Linda Mackie McCall, Peter D. Beitsch, Patrick W. Whitworth, Douglas S. Reintgen, Peter W. Blumencranz, A. Marilyn Leitch, Sukumal Saha, Kelly K. Hunt, Armando E. Giuliano
Journal: Journal of Clinical Oncology (2007)

The American College of Surgeons Oncology Group trial Z0011 was a prospective, randomized, multicenter trial comparing overall survival between patients with positive sentinel lymph nodes (SLNs) who did and did not undergo axillary lymph node dissection (ALND). The current study compares complications associated with SLN dissection (SLND) plus ALND, versus SLND alone.From May 1999 to December 2004, 891 patients were randomly assigned to SLND + ALND (n = 445) or SLND alone (n = 446). Information on wound infection, axillary seroma, paresthesia, brachial plexus injury (BPI), and lymphedema was available for 821 patients.Adverse surgical effects were reported in 70% (278 of 399) of patients after SLND + ALND and 25% (103 of 411) after SLND alone (P <or= .001). Patients in the SLND + ALND group had more wound infections (P <or= .0016), seromas (P <or= .0001), and paresthesias (P <or= .0001) than those in the SLND-alone group. At 1 year, lymphedema was reported subjectively by 13% (37 of 288) of patients after SLND + ALND and 2% (six of 268) after SLND alone (P <or= .0001). The difference between the two groups' lymphedema, assessed by arm measurements at 30 days (P = .36), 6 months (P = .22), and 1 year (P = .078), although close to the cutoff for significance at 1 year, was not significant. BPIs occurred in less than 1% of patients.In trial Z0011, the use of SLND + ALND resulted in more wound infections, axillary seromas, and paresthesias than SLND alone. Lymphedema was more common after SLND + ALND but was significantly different only by subjective report. The use of SLND alone resulted in fewer complications.
Abstract 170: Hippo Signaling Regulates Epicardial Derived Cell Fate through Controlling Mechanical Property
Authors: Yang Xiao, Min Zhang, Yuka Morikawa, James F Martin
Journal: Circulation Research (2014)

Epicardium is the outmost layer of heart and regulates heart development by contributing to the heart tissue and secreting signaling molecules. Epicardial-derived cells, EPDC, is a group of multi-potent cells mainly derive into cardiac fibroblasts and smooth muscle cells. Hippo signaling pathway controls organ growth through regulating cell proliferation. Yap, the effector of Hippo pathway has been shown to regulate mechanosensing and cell fate. However, the function of Hippo signaling in EPDC development has not been studied yet. To study the role of Hippo signaling in development of epicardium and EPDC, we used epicardial specific line, Wt1 CreERT2 , to conditionally delete the components of the pathway, Lats1/2. Cre activity was induced at embryonic day (E)11.5 and Lats1/2 CKO hearts exhibited disorganized coronary vasculature. We used genetic lineage tracing approach to track EPDC and revealed increased endothelial cells deriving from EPDC, suggesting that EPDC changed cell fate. We observed that shape of the epicardial cells became rounded with decreased F-actin in Lats1/2 CKO, which suggested that cell tension was reduced. Since mechanical properties of cellular microenvironment are known to regulate cell shape and influence cell fate determination, we hypothesize that Hippo pathway regulates mechanical property to control cell fate in EPDC. Transcription analysis showed that signals regulating cytoskeleton organization were disrupted, which suggests Hippo regulates cytoskeleton gene expression and affects mechanical force that cell sensed autonomously. Proliferation assay using EdU incorporation showed increased proliferation in EPDC of Lats1/2 CKO was observed, which suggests the changes of external tension cell sensed. To recapitulate the changes of external tension, we plated EPDC onto different stiffness substrate. EPDC of Lats1/2 CKO differentiated into endothelial cells on the soft substrate. On the other hand, Lats1/2 CKO did not derive endothelial cells on the hard substrate and wild type EPDC did not differentiate into endothelial cells on neither soft nor hard substrate. Taken together, our results suggested that Hippo pathway affected EPDC fate determination through controlling internal and external mechanical cues.
Views of Assisted Suicide From Several Nations
Authors: Pat Phillips
Journal: JAMA (1997)

QUALITY OF DEATH issues continue to drive an international dialogue about physician-assisted suicide. The medical-legal principles and concepts surrounding assisted death, particularly statutes in Australia and the state of Oregon, were among the issues explored at a conference held this summer in Dublin, Ireland, entitled "Comparative Perspectives on Law and Medicine." The meeting was sponsored by Loyola University Chicago Institute for Health Law, Chicago, Ill, and the health law section of the American Bar Association in cooperation with the Irish Legal Education and Research Trust and the health law section of the Canadian Bar Association. Introducing the session on physicianassisted suicide, John Blum, JD, associate dean of health law programs and professor of law at Loyola University, called the issue "important and controversial." Jocelyn Downie, LLM, director of the Health Law Institute at Dalhousie University in Halifax, Nova Scotia, called for a "respectful dialogue which does not devolve into the
Novel circuitry and molecular pathogenic mechanisms in Huntington's disease
Authors: X William Yang
Journal: Molecular Neurodegeneration (2012)

Methods HD is caused by a CAG repeat expansion encoding an expanded glutamine repeat near the N-terminus of the huntingtin protein. How mutant huntingtin (mhtt) causes progressive and selective degeneration of striatal and cortical neurons, leading to symptoms of HD, remains unclear. In this presentation, I will describe a novel reductionist approach to use Cre/LoxP conditional Bacterial Artificial Chromosome (BAC) transgenic mouse models expressing full-length mhtt to dissect circuitry and molecular pathogenic mechanisms in HD.
STUDIES ON THE AGENT OF INFECTIOUS HEPATITIS
Authors: Miles E. Drake, Albert W. Kitts, Mercer C. Blanchard, John D. Farquhar, Joseph Stokes, Werner Henle
Journal: The Journal of Experimental Medicine (1950)

The successful cultivation of the virus of infectious hepatitis in chick embryo tissue culture and in the amniotic cavity of the embryonated hen's egg is supported by a comparison of the disease induced in volunteers by the cultivated virus with hepatitis without jaundice resulting from experimental infection with natural infectious hepatitis virus. Both types of viral preparations produced illnesses in comparable percentages of volunteers (83 and 75 per cent, respectively) after similar average periods of incubation (24.4 and 23.4 days, respectively) and of similar average duration (28.3 and 27.6 days, respectively). The disease could be divided in both groups of patients into a primary stage, followed after a short interval of relative well being by the secondary stage. The illnesses in both instances were characterized by anorexia, nausea, vomiting, enlarged, tender livers and abnormal liver function tests, and frequently temperature elevations. They differed in that jaundice was observed in 31 per cent of the cases resulting from infection with natural virus but not in any patients infected with the cultivated virus.
Discordance among Commercially Available Diagnostics for Latent Tuberculosis Infection
Authors: James D. Mancuso, Gerald H. Mazurek, David Tribble, Cara Olsen, Naomi E. Aronson, Lawrence Geiter, Donald Goodwin, Lisa W. Keep
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

There is uncertainty regarding how to interpret discordance between tests for latent tuberculosis infection.The objective of this study was to assess discordance between commercially available tests for latent tuberculosis in a low-prevalence population, including the impact of nontuberculous mycobacteria.This was a cross-sectional comparison study among 2,017 military recruits at Fort Jackson, South Carolina, from April to June 2009. Several tests were performed simultaneously with a risk factor questionnaire, including (1) QuantiFERON-TB Gold In-Tube test, (2) T-SPOT.TB test, (3) tuberculin skin test, and (4) Battey skin test using purified protein derivative from the Battey bacillus.In this low-prevalence population, the specificities of the three commercially available diagnostic tests were not significantly different. Of the 88 subjects with a positive test, only 10 (11.4%) were positive to all three tests; 20 (22.7%) were positive to at least two tests. Bacille Calmette-Guérin vaccination, tuberculosis prevalence in country of birth, and Battey skin test reaction size were associated with tuberculin skin test-positive, IFN-γ release assay-negative test discordance. Increasing agreement between the three tests was associated with epidemiologic criteria indicating risk of infection and with quantitative test results.For most positive results the three tests identified different people, suggesting that in low-prevalence populations most discordant results are caused by false-positives. False-positive tuberculin skin test reactions associated with reactivity to nontuberculous mycobacteria and bacille Calmette-Guérin vaccination may account for a proportion of test discordance observed.
Mining microarray expression data by literature profiling
Authors: Damien Chaussabel, Alan Sher
Journal: Genome biology (2002)

The rapidly expanding fields of genomics and proteomics have prompted the development of computational methods for managing, analyzing and visualizing expression data derived from microarray screening. Nevertheless, the lack of efficient techniques for assessing the biological implications of gene-expression data remains an important obstacle in exploiting this information.To address this need, we have developed a mining technique based on the analysis of literature profiles generated by extracting the frequencies of certain terms from thousands of abstracts stored in the Medline literature database. Terms are then filtered on the basis of both repetitive occurrence and co-occurrence among multiple gene entries. Finally, clustering analysis is performed on the retained frequency values, shaping a coherent picture of the functional relationship among large and heterogeneous lists of genes. Such data treatment also provides information on the nature and pertinence of the associations that were formed.The analysis of patterns of term occurrence in abstracts constitutes a means of exploring the biological significance of large and heterogeneous lists of genes. This approach should contribute to optimizing the exploitation of microarray technologies by providing investigators with an interface between complex expression data and large literature resources.
GUBU: grotesque, unbelievable, bizarre, unprecedented
Authors: Liam Farrell
Journal: BMJ (2004)

“I don't really know what to say, doctor,” the patient said.

I closed my eyes in resignation; could he be any more ambiguous?

One of the skills in general practice is defining the problem. Anything, just anything, can walk though that surgery door. Tragic, comic, or unremittingly trivial—it's our job to reduce it to some form of manageable problem. But in terms of vagueness and sheer unhelpfulness it's hard to beat that opening gambit.

Country …
TLR3 deficiency impairs spinal cord synaptic transmission, central sensitization, and pruritus in mice
Authors: Tong Liu, Temugin Berta, Zhen-Zhong Xu, Chul-Kyu Park, Ling Zhang, Ning Lü, Qin Liu, Yang Liu, Yong-Jing Gao, Yen-Chin Liu, Qiufu Ma, Xinzhong Dong, Ru-Rong Ji
Journal: Journal of Clinical Investigation (2012)

Itch, also known as pruritus, is a common, intractable symptom of several skin diseases, such as atopic dermatitis and xerosis. TLRs mediate innate immunity and regulate neuropathic pain, but their roles in pruritus are elusive. Here, we report that scratching behaviors induced by histamine-dependent and -independent pruritogens are markedly reduced in mice lacking the Tlr3 gene. TLR3 is expressed mainly by small-sized primary sensory neurons in dorsal root ganglions (DRGs) that coexpress the itch signaling pathway components transient receptor potential subtype V1 and gastrin-releasing peptide. Notably, we found that treatment with a TLR3 agonist induces inward currents and action potentials in DRG neurons and elicited scratching in WT mice but not Tlr3–/– mice. Furthermore, excitatory synaptic transmission in spinal cord slices and long-term potentiation in the intact spinal cord were impaired in Tlr3–/– mice but not Tlr7–/– mice. Consequently, central sensitization–driven pain hypersensitivity, but not acute pain, was impaired in Tlr3–/– mice. In addition, TLR3 knockdown in DRGs also attenuated pruritus in WT mice. Finally, chronic itch in a dry skin condition was substantially reduced in Tlr3–/– mice. Our findings demonstrate a critical role of TLR3 in regulating sensory neuronal excitability, spinal cord synaptic transmission, and central sensitization. TLR3 may serve as a new target for developing anti-itch treatment.
Acremonium sclerotigenum-Acremonium egyptiacum: a multi-resistant fungal pathogen complicating the course of aplastic anaemia
Authors: J. Guitard‘, A. Degulys‘, G. Buot, A. Aline-Fardin, E. Dannaoui, B. Rio, J.P. Marie, S. Lapusan, C. Hennequin
Journal: Clinical Microbiology and Infection (2013)
Pregnancy following a single lung transplant.
Authors: D Parry, A Hextall, V P Robinson, N R Banner, M H Yacoub
Journal: Thorax (1996)

Successful pregnancy in a single lung transplant recipient has not been reported previously. The long term effect of pregnancy on graft function and management of deteriorating pulmonary function is not defined. This case describes the management, outcome, and problems encountered when a single lung transplant recipient developed a progressive deterioration in pulmonary function during pregnancy, attributed to accelerated obliterative bronchiolitis.
Utilizing the Second-Meal Effect in Type 2 Diabetes: Practical Use of a Soya-Yogurt Snack
Authors: Mei Jun Chen, Ana Jovanovic, Roy Taylor
Journal: Diabetes Care (2010)

To evaluate the effect of a prebreakfast high-protein snack upon postbreakfast hyperglycemia.We studied 10 men and women with diet- and/or metformin-controlled type 2 diabetes. Metabolic changes after breakfast were compared between 2 days: breakfast taken only and soya-yogurt snack taken prior to breakfast.There was a significant lower rise in plasma glucose on the snack day. The incremental area under the glucose curve was 450 ± 55 mmol · min/l on the snack day compared with 699 ± 99 mmol · min/l on the control day (P = 0.013). The concentration of plasma free fatty acids immediately before breakfast correlated with the increment in plasma glucose (r = 0.50, P = 0.013).Consuming a high-protein prebreakfast snack results in almost 40% reduction of postprandial glucose increment. The second-meal effect can be applied simply and practically to improve postbreakfast hyperglycemia in people with type 2 diabetes.