tbuckley/cabot-search huggingface dataset:
Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia &amp; Lymphoma (TACL) Study
Authors: Yoav H. Messinger, Paul S. Gaynon, Richard Sposto, Jeannette van der Giessen, Elena Eckroth, Jemily Malvar, Bruce C. Bostrom
Journal: Blood (2012)
APHONIA DUE TO CHRONIC ALCOHOLISM. PARALYSIS OF THE LATERAL CRICO-ARYTENOIDS.
Authors: ETHELBERT CARROLL MORGAN
Journal: JAMA (1884)

Read to the Section of Ophthalmology, Otology and Laryngology of American Medical Association, May 8, 1884. There is no morbid condition involving the vocal organs possessing a more varied pathogeny than paralysis of the lateral crico-arytenoid muscles, the functional aphonia of pre-laryngoscopic authors. No disease is more doubtful in its amenability to therapeutic measures, the restoration of voice in some instances following the introduction of the laryngoscopic mirror; in others baffling all our resources. That motor disturbances of the muscles under discussion resulting from fright, mental emotion, anæmia, chlorosis, dysmenorrhœa, intestinal irritation, rheumatism, syphilis, diphtheria, hysteria, and reflex influences do occur is a fact generally admitted and frequently observed by the laryngologist. Lead, arsenic, phosphorus, opium, and belladonna, have all been accredited with having caused palsy of the various laryngeal muscles. These cases, however, are greatly scattered throughout literature, and occasionally lack important details. "The influence of certain substances taken
Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells
Authors: Markus D. Siegelin, Takehiko Dohi, Christopher M. Raskett, Gregory M. Orlowski, Christine M. Powers, Candace A. Gilbert, Alonzo H. Ross, Janet Plescia, Dario C. Altieri
Journal: Journal of Clinical Investigation (2011)

Fine tuning of the protein folding environment in subcellular organelles, such as mitochondria, is important for adaptive homeostasis and may participate in human diseases, but the regulators of this process are still largely elusive. Here, we have shown that selective targeting of heat shock protein-90 (Hsp90) chaperones in mitochondria of human tumor cells triggered compensatory autophagy and an organelle unfolded protein response (UPR) centered on upregulation of CCAAT enhancer binding protein (C/EBP) transcription factors. In turn, this transcriptional UPR repressed NF-κB–dependent gene expression, enhanced tumor cell apoptosis initiated by death receptor ligation, and inhibited intracranial glioblastoma growth in mice without detectable toxicity. These data reveal what we believe to be a novel role of Hsp90 chaperones in the regulation of the protein-folding environment in mitochondria of tumor cells. Disabling this general adaptive pathway could potentially be used in treatment of genetically heterogeneous human tumors.
Hemodynamic determinants of pulmonary valve motion during systole in experimental pulmonary hypertension.
Authors: M Tahara, H Tanaka, S Nakao, H Yoshimura, S Sakurai, C Tei, T Kashima
Journal: Circulation (1981)

To clarify the determinants of pulmonary valve (PV) motion in pulmonary hypertension, we examined the correlations among PV echo patterns, the pulmonary artery (PA) flow curve just above the PA orifice and the pulmonary artery-right ventricle (PA-RV) pressure gradient. By constricting the PA, we could produce a variety of PV echo patterns, including midsystolic semiclosure in open-chest dogs. Throughout the experiments, the PV echo pattern and PA flow curve were similar in pattern and timing. When the PV echo showed midsystolic semiclosure with reopening. The PA flow curve showed a transient decrease followed by a transient increase during midsystole. The PA-RV pressure gradient became transiently positive (PA pressure greater than RV pressure) and then negative in midsystole only when the PV echo showed midsystolic semiclosure with reopening. In conclusion, PV motion during systole may be instantaneously determined by PA flow change and the PA-RV pressure gradient during the cardiac cycle in experimental pulmonary hypertension.
Interpretation of positive transcription-mediated amplification test results from polymerase chain reaction-negative samples obtained after treatment of chronic hepatitis C
Authors: Chihiro Morishima, Timothy R. Morgan, James E. Everhart, Elizabeth C. Wright, Minjun C. Apodaca, David R. Gretch, Mitchell L. Shiffman, Gregory T. Everson, Karen L. Lindsay, William M. Lee, Anna S. F. Lok, Jules L. Dienstag, Marc G. Ghany, Teresa M. Curto
Journal: Hepatology (2008)

The Siemens VERSANT® transcription-mediated amplification (TMA) assay is extremely sensitive for the detection of hepatitis C virus (HCV) RNA in serum. Eleven of 180 subjects in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial who achieved polymerase chain reaction (PCR)-defined sustained virological response (SVR) at week 72 also had TMA-positive results from the same blood draw; six were positive on repeat testing. We report the follow-up on these 11 patients, and the reproducibility of TMA test results from PCR-negative samples in relationship to antiviral treatment outcome. Peginterferon and ribavirin treatment was initiated in 1145 prior interferon nonresponders with advanced hepatic fibrosis. Treatment was continued for 48 weeks if patients had undetectable HCV RNA by PCR at treatment week 20. Frozen serum samples from weeks 12, 20, 24, 48, and 72 were subsequently tested by TMA. Nine of the 11 patients returned for testing (median, 30 months after the week 72 visit), and all had undetectable HCV RNA by TMA and PCR. Among 759 PCR-negative samples obtained during treatment that were tested twice by TMA, 17% overall exhibited consistently positive results, and 21% exhibited inconsistently positive results. SVR was more likely if TMA was consistently negative than if consistently or inconsistently positive. With continued treatment, patients with inconsistently positive TMA results were more likely to become TMA-negative than TMA-positive (P < 0.0001). Conclusion: In PCR-negative samples, positive TMA results may indicate the presence of low levels of HCV RNA. However, because patients with positive TMA results may achieve SVR, management decisions during therapy should not be based on a single positive TMA test result. (HEPATOLOGY 2008.)
FDA warns Merck over its promotion of rofecoxib
Authors: D. Josefson
Journal: BMJ (2001)

The US Food and Drug Administration has issued a warning letter to the pharmaceutical company Merck for misrepresenting the safety of their blockbuster anti-inflammatory drug, rofecoxib (Vioxx).

Rofecoxib, a selective cyclo-oxygenase-2 (COX 2) inhibitor, was approved by the administration in May 1999 for the relief of acute pain, osteoarthritis, and dysmenorrhoea. The drug was heavily promoted by Merck and touted as safer than and superior to non-selective, non-steroidal anti-inflammatory drugs such as ibuprofen and naproxen.

In its …
A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease
Authors: Rachel L Graham, Michelle M Becker, Lance D Eckerle, Meagan Bolles, Mark R Denison, Ralph S Baric
Journal: Nature Medicine (2012)

Live, attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus (CoV) replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3'→5' exonuclease (ExoN) activity that probably functions in RNA proofreading. In this study we demonstrate that engineered inactivation of severe acute respiratory syndrome (SARS)-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged and immunocompromised mice. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. ExoN inactivation has potential for broad applications in the stable attenuation of CoVs and, perhaps, other RNA viruses.
Rehabilitation, Music and Human Well-Being
Authors: Sheldon Berrol
Journal: JAMA (1990)

In the attempt to provide a broad perspective on all aspects of music and its applications to medicine, this edited volume simply strays too far. There is great variability in the sometimes pedantic presentation and style. An excellent review of the historical perspective introduces the volume but then proceeds to place some modern-day theoretic possibilities within the framework of scientific fact. Itoh and Lee, in the section on "Epidemiology and Music," posit that people ideally should have perfect health throughout a lifetime. One may reasonably argue that the search for rarely attainable perfection may in itself contribute to infirmity, at least in a psychological sense. The position of Rodgers, quoted later in the chapter, which suggests optimum health as the goal, appears far more realistic (although the authors disagree). In Wilson's review of kinesiologic theory, the suggestion that true ballistic movements are terminated only by extrinsic barriers fails to incorporate
The Nature of the PR Interval
Authors: F. A. Roberge, R. A. Nadeau, T. N. James
Journal: Cardiovascular Research (1968)

Selective perfusion of the sinus and A-V nodes in dogs and simulation experiments with a system of two interacting relaxation oscillators were used to study the nature of the PR interval. The PR interval duration appears to be composed of a relatively fixed conduction delay, and of a labile portion determined by the local excitability of the A-V node region.
Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart.
Authors: R Coronel, J W Fiolet, J G Wilms-Schopman, T Opthof, A F Schaapherder, M J Janse
Journal: Circulation (1989)

We studied the relation between [K+]o and the electrophysiologic changes during a "Harris two-stage ligation," which is an occlusion of a coronary artery, preceded by a 30-minute period of 50% reduction of flow through the artery. This two-stage ligation has been reported to be antiarrhythmic. Local direct current electrograms and [K+]o signals from up to 48 intramural sites were simultaneously recorded in isolated, perfused dog hearts. A second period of one-stage ligation was compared with a consecutive two-stage ligation because reproducibility in [K+]o and electrophysiologic changes are established only after the first period of ischemia. In control experiments, no difference was found between the second and third period of one-stage ligation in the electrophysiologic changes and in increases in [K+]o. After complete occlusion during two-stage ligation, activation block in the ischemic tissue occurred about 6 minutes earlier than during one-stage ligation, but the average potassium concentration at which block occurred was identical. This [K+]o during total ischemia was achieved earlier during two-stage ligation than during one-stage ligation. No indication was found for a large decrease of intracellular potassium content during the period of low flow perfusion. Early activation block may explain the previously reported reduced incidence of ventricular fibrillation during two-stage ligation.
Evidence for altered central noradrenergic function in experimental acute liver failure in the rat
Authors: Adrianna Michalak, Christopher Rose, Paul N. Buu, Roger F. Butterworth
Journal: Hepatology (1998)

These is increasing evidence to suggest that central noradrenergic mechanisms may contribute to the central nervous system manifestations of acute liver failure. To further elucidate this possibility, extracellular brain concentrations of the monoamines, noradrenaline (NA), dopamine (DA), and serotonin, were measured by high-performance liquid chromatography with electrochemical detection in microdialysates from the extracellular compartment of frontal cortex in rats with acute (ischemic) liver failure at various times during the progression of encephalopathy and brain edema, as well as in obligate control groups of animals. In addition, binding sites for the noradrenergic receptor subtype ligands, [3H]-prazosin (α1 sites), [3H]-RX821002 (α2 sites), and [125]I-iodopindolol (β sites), were assessed using quantitative receptor autoradiography in regions of the brains of rats at coma stage of acute liver failure and of control groups of animals. Coma stages of encephalopathy in acute liver failure were associated with selectively increased noradrenaline concentrations (P < .05) and a concomitant selective loss of α1 and β1 sites in frontal cortex and thalamus. These findings add to a growing body of evidence that central noradrenergic function is modified in acute liver failure and suggest that α1/β1 receptor–mediated noradrenergic mechanisms may play a role in the pathogenesis of brain edema and encephalopathy in this condition.
Psychiatry services for elderly people. Doctors should be in the front line.
Authors: D J Jolley
Journal: BMJ (1993)

Radiologists' advice about breast lumps EDITOR,-I write to correct the headline in the news section about the warning on unnecessary x ray examinations.'The advice regarding women with breast lumps is for any age, not just women under 50.It is not new but has been included in the second edition of our booklet of advice for referring clinicians, which is new.2There is no new joint report from the college and the National Radio- logical Protection Board on this topic.The college did, however, issue such a report in 19903: this endorsed the recommendation of the Forrest report on breast screening that it should be reserved for women aged 50-64.4
Effect of Prenatal Exposure to Polychlorinated Biphenyls on Incidence ofAcute Respiratory Infections in Preschool Inuit Children
Authors: Frédéric Dallaire, Éric Dewailly, Carole Vézina, Gina Muckle, Jean-Philippe Weber, Suzanne Bruneau, Pierre Ayotte
Journal: Environmental Health Perspectives (2006)

We set out to assess whether environmental prenatal exposure to polychlorinated biphenyls (PCBs) is associated with incidence of acute respiratory infections in preschool Inuit children.We reviewed the medical charts of 343 children from 0 to 5 years of age and evaluated the associations between PCB-153 concentration in umbilical cord plasma and the incidence rates of acute otitis media (AOM) and of upper and lower respiratory tract infections (URTIs and LRTIs, respectively).The incidence rates of AOM and LRTIs were positively associated with prenatal exposure to PCBs. Compared with children in the first quartile of exposure (least exposed), children in fourth quartile (most exposed) had rate ratios of 1.25 (p<0.001) and 1.40 (p<0.001) for AOM and LRTIs, respectively. There was no association between prenatal PCB exposure and incidence rate of URTIs or hospitalization.Prenatal exposure to PCBs could be responsible for a significant portion of respiratory infections in children of this population.
Computational Prediction of MicroRNAs from <i>Toxoplasma Gondii</i> Potentially Regulating the Hosts’ Gene Expression
Authors: Müşerref Duygu Saçar, Caner Bağcı, Jens Allmer
Journal: Genomics Proteomics & Bioinformatics (2014)

Abstract MicroRNAs (miRNAs) were discovered two decades ago, yet there is still a great need for further studies elucidating their genesis and targeting in different phyla. Since experimental discovery and validation of miRNAs is difficult, computational predictions are indispensable and today most computational approaches employ machine learning. Toxoplasma gondii, a parasite residing within the cells of its hosts like human, uses miRNAs for its post-transcriptional gene regulation. It may also regulate its hosts’ gene expression, which has been shown in brain cancer. Since previous studies have shown that overexpressed miRNAs within the host are causal for disease onset, we hypothesized that T. gondii could export miRNAs into its host cell. We computationally predicted all hairpins from the genome of T. gondii and used mouse and human models to filter possible candidates. These were then further compared to known miRNAs in human and rodents and their expression was examined for T. gondii grown in mouse and human hosts, respectively. We found that among the millions of potential hairpins in T. gondii, only a few thousand pass filtering using a human or mouse model and that even fewer of those are expressed. Since they are expressed and differentially expressed in rodents and human, we suggest that there is a chance that T. gondii may export miRNAs into its hosts for direct regulation.
Association study of mast cell chymase polymorphisms with atopy
Authors: S. Weidinger, L. Rümmler, N. Klopp, S. Wagenpfeil, H. J. Baurecht, G. Fischer, R. Holle, A. Gauger, T. Schäfer, T. Jakob, M. Ollert, H. Behrendt, H. E. Wichmann, J. Ring, T. Illig
Journal: Allergy (2005)

Background: Atopic disorders are the result of complex interactions between genetic and environmental factors. Associations analyses between the promoter polymorphism rs1800875 in the mast cell chymase gene ( CMA1 ) and atopy‐related phenotypes have yielded inconsistent results. Methods: We sequenced the CMA1 locus in 24 unrelated healthy individuals with serum IgE levels &lt;50% percentile and 24 individuals with atopic eczema and serum IgE levels &gt;90% percentile. Seven CMA1 single nucleotide polymorphisms (SNPs) were evaluated for evidence of associations with atopic phenotypes within a large population of German adults ( n = 1875). Subjects were phenotyped by standardized questionnaires and interviews, skin prick testing and serum IgE measurements. Genotyping was performed using MALDI‐TOF MS (Matrix‐Assisted Laser Desorption Ionization–Time of Flight mass spectrometry). Results: Promoter polymorphism rs1800875 was significantly associated with atopic eczema. No associations between any other single SNP and atopic phenotypes could be detected. Haplotype reconstruction revealed four of 128 possible haplotypes reaching estimated frequencies of 3% or more. Two of these haplotypes showed a borderline‐significant association with atopic eczema, which did not remain significant after correction for multiple testing. Conclusions: Results confirm previous observations of a significant association between the CMA1 promoter polymorphism rs1800875 and atopic eczema, but not with serum IgE levels, and support the hypothesis that CMA1 serves as candidate gene for atopic eczema.
Do locum duties help or hinder acquisition of clinical knowledge by final year medical students?
Authors: M Goldman, M X Gannon, K L Woods
Journal: BMJ (1985)

pharynx and of the epiglottis, which prevented an adequate view of the vocal cords.Tracheotomy was performed; the trachea looked normal, and a 5 5 mm Shiley tracheostomy tube was inserted.The child was nuirsed in the intensive therapy unit but refused to feed during the next 48 hours.Further endoscopy showed a large, sloughing ulcer covering two thirds of the epiglottis.There was a similar ulcer in the midline of the posterior pharyngeal wall, extending as far as the crico- pharyngeus.The vocal cords and oesophagus were normal.A nasogastric tube was passed for feeding and the tracheostomy tube reduced to 3-5 mm.Decannulation was performed 48 hours later.Oral feeding restarted at 10 days, and he was discharged 12 days after admission. 1
Partial hydronephrosis due to pressure from normal renal arteries.
Authors: F. Starer
Journal: BMJ (1968)

DISCUSSIONThe above work is believed to present direct evidence that the Ph' chromosome is present in the erythroid as well as in the myeloid cell series.Several workers (Tough et al., 1963; Trujillo and Ohno, 1963 ; Whang et al., 1963) have, on the basis of good circumstantial evidence, postulated the probable involvement of megakaryoblasts.It therefore seems reasonable to suggest, on the basis of evidence to date, that the erythroid, myeloid, and possibly the megakaryocytic cell series are derived from a stem cell common to all three types.Two further patients with chronic granulocytic leukaemia are at present being studied, and a more detailed report is in preparation. SUMMARYChromosome preparations of the bone marrow of a patient with chronic granulocytic leukaemia were made after the cells had been cultured with 59Fe or 55Fe.The autoradiograms of these preparations give direct evidence that the Ph' chromosome is present in the erythroid cell series.
WT1 peptide vaccination following allogeneic stem cell transplantation in pediatric leukemic patients with high risk for relapse: successful maintenance of durable remission
Authors: Y Hashii, E Sato-Miyashita, R Matsumura, S Kusuki, H Yoshida, H Ohta, N Hosen, A Tsuboi, Y Oji, Y Oka, H Sugiyama, K Ozono
Journal: Leukemia (2011)
Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors
Authors: Ioanna Dimopoulou, Stylianos Tsagarakis, Maria Theodorakopoulou, Evangelia Douka, Maria Zervou, Andreas T. Kouyialis, Nikolaos Thalassinos, Charis Roussos
Journal: Intensive Care Medicine (2004)
Transportation Noise and Blood Pressure in a Population-Based Sample of Adults
Authors: Julia Dratva, Harish C. Phuleria, Maria Foraster, Jean-Michel Gaspoz, Dirk Keidel, Nino Künzli, L.-J. Sally Liu, Marco Pons, Elisabeth Zemp, Margaret W Gerbase, Christian Schindler
Journal: Environmental Health Perspectives (2011)

There is some evidence for an association between traffic noise and ischemic heart disease; however, associations with blood pressure have been inconsistent, and little is known about health effects of railway noise.We aimed to investigate the effects of railway and traffic noise exposure on blood pressure; a secondary aim was to address potentially susceptible subpopulations.We performed adjusted linear regression analyses using data from 6,450 participants of the second survey of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA 2) to estimate the associations of daytime and nighttime railway and traffic noise (A-weighted decibels) with systolic blood pressure (SBP) and diastolic blood pressure (DBP; millimeters of mercury). Noise data were provided by the Federal Office for the Environment. Stratified analyses by self-reported hypertension, cardiovascular disease (CVD), and diabetes were performed.Mean noise exposure during the day and night was 51 dB(A) and 39 dB(A) for traffic noise, respectively, and 19 dB(A) and 17 dB(A) for railway noise. Adjusted regression models yielded significant effect estimates for a 10 dB(A) increase in railway noise during the night [SBP β = 0.84; 95% confidence interval (CI): 0.22, 1.46; DBP β = 0.44; 95% CI: 0.06, 0.81] and day (SBP β = 0.60; 95% CI: 0.07, 1.13). Additional adjustment for nitrogen dioxide left effect estimates almost unchanged. Stronger associations were estimated for participants with chronic disease. Significant associations with traffic noise were seen only among participants with diabetes.We found evidence of an adverse effect of railway noise on blood pressure in this cohort population. Traffic noise was associated with higher blood pressure only in diabetics, possibly due to low exposure levels. The study results imply more severe health effects by transportation noise in vulnerable populations, such as adults with hypertension, diabetes, or CVD.
Dermatitis herpetiformis and gluten-free diet.
Authors: J Marks, S Shuster
Journal: BMJ (1970)

MBITISAUNALThough the renin content of a kidney is stated to be reduced by denervation and steroids (as in kidney allotransplantation presumably) there appears (in a large proportion of rejection episodes) little interfer- ence with the mechanism which allows hypertensive states to be reached.So far as I can determine by experiment, the role of renin in renal failure remains an interesting speculation lacking direct evi- dence in its support.There is, however, some direct evidence against its primary involvement.