tbuckley/cabot-search huggingface dataset:
Evolving Strategies for the Management of Atrial Fibrillation
Authors: N. A. Mark Estes
Journal: JAMA (1992)

Management strategies for the most common sustained cardiac arrhythmia,<sup>1,2</sup>atrial fibrillation, have undergone considerable evolution over the last several years. The objectives of therapy are to slow ventricular rate and restore and maintain sinus rhythm. Prevention of symptoms and reduction in the risk of complications such as stroke are therapeutic goals with agents that slow atrioventricular nodal conduction, antiarrhythmic agents, and anticoagulants. The utility of digoxin for rate control has been questioned with recent studies suggesting that this former mainstay of therapy may now play a subsidiary role.<sup>3</sup>β-Blockers and calcium channel blockers are now frequently used for slowing ventricular response. Concerns regarding the safety of quinidine have been raised by a recent meta-analysis showing an increased mortality in patients randomized to quinidine therapy or placebo for atrial fibrillation,<sup>4</sup>although there are many limitations to this retrospective analysis. These safety concerns have been extended with recent observations
Fatal autoimmunity in mice reconstituted with human hematopoietic stem cells encoding defective FOXP3
Authors: Jeremy A. Goettel, Subhabrata Biswas, Willem S. Lexmond, Ada Yeste, Laura Passerini, Bonny Patel, Siyoung Yang, Jiusong Sun, Jodie Ouahed, Dror S. Shouval, Katelyn J. McCann, Bruce H. Horwitz, Diane Mathis, Edgar L. Milford, Luigi D. Notarangelo, Maria-Grazia Roncarolo, Edda Fiebiger, Wayne A. Marasco, Rosa Bacchetta, Francisco J. Quintana, Sung-Yun Pai, Christoph Klein, Aleixo M. Muise, Scott B. Snapper
Journal: Blood (2015)
Increased Myocardial Gene Expression of Tumor Necrosis Factor-α and Nitric Oxide Synthase-2
Authors: Dinesh K. Kalra, Xi Zhu, Mahesh K. Ramchandani, Gerald Lawrie, Michael J. Reardon, Dorellyn Lee-Jackson, William L. Winters, Natarajan Sivasubramanian, Douglas L. Mann, William A. Zoghbi
Journal: Circulation (2002)

Whether cardioinhibitory cytokines are elevated in regions of hibernating myocardium and account in part for the depression in resting function is currently not known. Methods and Results- Thirteen patients with stable ischemic ventricular dysfunction scheduled for bypass surgery underwent preoperative dobutamine echocardiography (DE) and intraoperative myocardial biopsies. The numbers of copies of mRNA for the negatively inotropic cytokines tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (NOS2) were quantified by reverse transcription-polymerase chain reaction. In normal segments, myocardial TNF-alpha was barely detectable (1.2+/-0.4 copies per 10(6) copies of beta-actin). A 13.7-fold increase in myocardial TNF-alpha was observed in dysfunctional segments with a biphasic response to DE (contractile reserve and ischemia) and was highest (45.5-fold) in segments with ischemia and without contractile reserve (P<0.001). A similar graded increase was seen for NOS2. Cytokine results were also similar if analysis was performed using recovery of function at 3 months as the index of viability. The change in serum TNF-alpha and nitrite levels from baseline to 3 months after surgery correlated inversely with both the change in ejection fraction and the number of DE viable segments (r=-0.92 to -0.93; P<0.001).TNF-alpha and NOS2 gene expression is regionally upregulated in hibernating myocardium to a level intermediate between that of normal regions and ischemic regions without contractile reserve. This, along with a decline in serum cytokine levels after revascularization proportional to the extent of myocardial viability, suggests a contributing role for cardioinhibitory cytokines in the observed depression of function seen in hibernating myocardium.
PREVENTION OF DETERIORATION OF RENAL AND SENSORY-NERVE FUNCTION BY MORE INTENSIVE MANAGEMENT OF INSULIN-DEPENDENT DIABETIC PATIENTS
Authors: R.R. Holman, V. Mayon-White, C. Orde-Peckar, J. Steemson, B. Smith, K. Mcpherson, C. Rizza, A.H. Knight, T.L. Dornan, J. Howard-Williams, L. Jenkins, R. Rolfe, D. Barbour, Pyw Poon, J.I. Mann, A.J. Bron, R.C. Turner
Journal: The Lancet (1983)
Loss of Lkb1 Provokes Highly Invasive Endometrial Adenocarcinomas
Authors: Cristina M. Contreras, Sushma Gurumurthy, J. Marshall Haynie, Lane J. Shirley, Esra A. Akbay, Shana N. Wingo, John O. Schorge, Russell R. Broaddus, Kwok-Kin Wong, Nabeel Bardeesy, Diego H. Castrillon
Journal: Cancer Research (2008)

Abstract Mutations in the LKB1 tumor suppressor gene result in the Peutz-Jeghers syndrome, an autosomal dominant condition characterized by hamartomatous polyps of the gastrointestinal tract and a dramatically increased risk of epithelial malignancies at other sites, including the female reproductive tract. Here we show that female mice heterozygous for a null Lkb1 allele spontaneously develop highly invasive endometrial adenocarcinomas. To prove that these lesions were indeed due to Lkb1 inactivation, we introduced an adenoviral Cre vector into the uterine lumen of mice harboring a conditional allele of Lkb1. This endometrial-specific deletion of the Lkb1 gene provoked highly invasive and sometimes metastatic endometrial adenocarcinomas closely resembling those observed in Lkb1 heterozygotes. Tumors were extremely well differentiated and histopathologically distinctive and exhibited alterations in AMP-dependent kinase signaling. Although Lkb1 has been implicated in the establishment of cell polarity, and loss of polarity defines most endometrial cancers, Lkb1-driven endometrial cancers paradoxically exhibit (given their highly invasive phenotype) normal cell polarity and apical differentiation. In human endometrial cancers, Lkb1 expression was inversely correlated with tumor grade and stage, arguing that Lkb1 inactivation or down-regulation also contributes to endometrial cancer progression in women. This study shows that Lkb1 plays an important role in the malignant transformation of endometrium and that Lkb1 loss promotes a highly invasive phenotype. [Cancer Res 2008;68(3):759–66]
Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase
Authors: Ning Gao, Amit Budhraja, Senping Cheng, Hua Yao, Zhuo Zhang, Xianglin Shi
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To characterize the functional role of c-Jun NH2-terminal kinase (JNK) and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in human leukemia cells by using pharmacologic and genetic approaches. Experimental Design: Jurkat cells were treated with various concentrations of GSE for 12 and 24 h or with 50 μg/mL GSE for various time intervals, after which apoptosis, caspase activation, and cell signaling pathways were evaluated. Parallel studies were done in U937 and HL-60 human leukemia cells. Results: Exposure of Jurkat cells to GSE resulted in dose- and time-dependent increase in apoptosis and caspase activation, events associated with the pronounced increase in Cip1/p21 protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by pharmacologic inhibitor (e.g., SP600125) or genetic (e.g., small interfering RNA) approaches displayed significant protection against GSE-mediated lethality in Jurkat cells. Conclusions: The result of the present study showed that GSE induces apoptosis in Jurkat cells through a process that involves sustained JNK activation and Cip1/p21 up-regulation, culminating in caspase activation.
Neonatal IgE levels and three different blood sampling techniques
Authors: G. Lilja, C. G. M. Magnusson, S. G. O. Johansson, E. Kusoffsky, H. Öman
Journal: Allergy (1992)

Comparison was made of IgE and IgA levels in aspirated and gravity‐collected cord blood (CB) from the umbilical vein and in capillary blood samples collected on the 4‐5th day of life among 21 infants with atopic heredity. The IgA levels, but not the IgE levels, were significantly (p&lt; 0.001) lower at days 4‐5 of life than at delivery. Further, there were significantly (p&lt;0.05) more infants with decreasing IgA levels (20/21; 95%) than IgE levels (9/15; 60% of those with detectable IgE, i.e., ≥ 0.125 kU/1). These observations, together with the highly significant correlation observed between IgE in aspirated CB samples and at 4–5 days of age, suggest active IgE synthesis during the prenatal and postnatal periods. Contamination of CB with maternal blood, defined as an increased CBIgA level (≥ 14.1 μg/ml), was found in 3 (14%) CB samples, all of which were gravity‐collected. Of 4 CB samples (gravity‐collected) with elevated IgE (i.e., ≥ 0.9kU/l), 2 had suspected maternal contamination. Therefore, aspiration of CB or capillary collection at 4‐5 days of age should be preferred for allergy prediction. If gravity collection is used, contamination should be investigated by determining IgA in all CB samples with IgE concentrations exceeding the cut‐off point.
Bronchiolitis obliterans organizing pneumonia associated with chlamydial infection
Authors: JL Diehl, M Gisselbrecht, G Meyer, D Israel-Biet, H Sors
Journal: European Respiratory Journal (1996)

A 70 year old man presented with symptoms and laboratory findings suggestive of chlamydial pneumonia. Despite adequate antibiotic therapy, his condition did not improve and transbronchial biopsies disclosed a typical feature of bronchiolitis obliterans organizing pneumonia (BOOP). After initiation of corticosteroid therapy, there were marked clinical and radiographic improvements. This report demonstrates that chlamydial infection may be associated with BOOP.
&lt;TITLE&gt;Survival After AIDS Diagnosis in Adolescents and Adults During the Treatment Era, United States, 1984-1997&lt;/TITLE&gt;
Authors: L M Lee, J M Karon, R Selik, J J Neal, P L Fleming
Journal: JAMA (2001)

Declines in the number of acquired immunodeficiency syndrome (AIDS) deaths were first observed in 1996, attributed to improvements in antiretroviral therapy and an increase in the proportion of persons receiving therapy.To examine national trends in survival time among persons diagnosed as having AIDS in 1984-1997.Retrospective cohort study using data from a population-based registry of AIDS cases and deaths reported in the United States.Months of survival after AIDS diagnosis through December 31, 1998, compared by year of diagnosis.Among 394 705 persons with an AIDS-defining opportunistic illness (OI) diagnosed in 1984-1997, median survival time improved from 11 months for 1984 diagnoses to 46 months for 1995 diagnoses. Among persons with an OI diagnosed in 1996 and 1997, 67% were alive at least 36 months after diagnosis and 77% were alive at least 24 months after diagnosis, respectively. Among 296 621 AIDS cases diagnosed during 1993-1997, 65% were based on immunologic criteria and 35% on OI criteria; 80% were among men; and 42% were among non-Hispanic blacks, 40% among non-Hispanic whites, 17% among Hispanics, 1% among Asians/Pacific islanders, and less than 1% among American Indians/Alaska natives. The probability of surviving at least 24 months increased from 67% for those with immunologic diagnoses in 1993 to 90% in 1997 and from 49% for those with OI diagnoses in 1993 to 80% in 1997. Survival time increased with each year of diagnosis from 1984 to 1997 for blacks, whites, and Hispanics. The greatest annual survival gains occurred among persons receiving an AIDS diagnosis in 1995 and 1996.Survival time after AIDS diagnosis improved from 1984 to 1997. While AIDS incidence is declining, improved survival times present a growing public health challenge as the number of persons living with chronic human immunodeficiency virus disease/AIDS increases.
Efficacy, Safety, and Tolerability of Pregabalin Treatment for Painful Diabetic Peripheral Neuropathy
Authors: Roy Freeman, Edith Durso-DeCruz, Birol Emir
Journal: Diabetes Care (2008)

To evaluate the efficacy, safety, and tolerability of pregabalin across the effective dosing range, to determine differences in the efficacy of three times daily (TID) versus twice daily (BID) dosage schedules, and to use time-to-event analysis to determine the time to onset of a sustained therapeutic effect using data from seven trials of pregabalin in painful diabetic peripheral neuropathy (DPN).Data were pooled across seven double-blind, randomized, placebo-controlled trials using pregabalin to treat painful DPN with dosages of 150, 300, and 600 mg/day administered TID or BID. Only one trial included all three of these dosages, and TID dosing was used in four. All studies shared fundamental selection criteria, and treatment durations ranged from 5 to 13 weeks.Pooled analysis showed that pregabalin significantly reduced pain and pain-related sleep interference associated with DPN (150, 300, and 600 mg/day administered TID vs. placebo, all P < or = 0.007). Only the 600 mg/day dosage showed efficacy when administered BID (P < or = 0.001). Pain and sleep interference reductions associated with pregabalin appear to be positively correlated with dosage; the greatest effect was observed in patients treated with 600 mg/day. Kaplan-Meier analysis revealed that the median time to onset of a sustained (> or =30% at end point) 1-point improvement was 4 days in patients treated with pregabalin at 600 mg/day, 5 days in patients treated with pregabalin at 300 mg/day, 13 days in patients treated with pregabalin at 150 mg/day, and 60 days in patients receiving placebo. The most common treatment-emergent adverse events were dizziness, somnolence, and peripheral edema.Treatment with pregabalin across its effective dosing range is associated with significant, dose-related improvement in pain in patients with DPN.
Marrow mass and distribution in murine skeletons cleaned by beetles as compared to cut up carcasses and a further simplification of the latter technique
Authors: Dane R. Boggs, Kenneth D. Patrene
Journal: American Journal of Hematology (1986)

Abstract Distribution of 59 Fe into various bone groups of the complete murine skeleton was studied using two methods of dividing up the bones: 1) our previously reported technique of simply cutting up a skinned, eviscerated carcass and 2) separating bones from skeletons cleaned of overlying tissue by beetles, Dermestes species. The total percentage of injected 59 Fe recovered in the sum of all skeletal parts, the percentage of total skeletal 59 Fe found in each bone group, and the overall accuracy of determining these values were quite similar for the two techniques. The only statistically significant difference shown was a modest decrease in the percentage of total skeletal iron found in ribs plus sternum plus cervical and thoracic spine in beetle‐cleaned as compared to cut up groups and we would not consider this to be of biological significance. Cutting up carcasses is the simpler of the two techniques but there are circumstances in which beetle digestion would be advantageous. In addition, we collected data on the reproducibility and precision of determining the percentage of 59 Fe injected which is found in a „pulled off”︁ foreleg plus scapula and of the distribution of 59 Fe within three cut up pieces from the leg and within the scapula. These data can be used as a measure of overall changes in marrow mass and/or distribution, or at least they can be used as a screening procedure to detect such. This simple procedure adds potentially useful values for fully interpreting hematopoietic changes in the mouse.
Neutrophil-related factors as biomarkers in EAE and MS
Authors: Julie M. Rumble, Amanda K. Huber, Gurumoorthy Krishnamoorthy, Ashok Srinivasan, David A. Giles, Xu Zhang, Lu Wang, Benjamin M. Segal
Journal: The Journal of Experimental Medicine (2015)

A major function of T helper (Th) 17 cells is to induce the production of factors that activate and mobilize neutrophils. Although Th17 cells have been implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE), little attention has been focused on the role of granulocytes in those disorders. We show that neutrophils, as well as monocytes, expand in the bone marrow and accumulate in the circulation before the clinical onset of EAE, in response to systemic up-regulation of granulocyte colony-stimulating factor (G-CSF) and the ELR+ CXC chemokine CXCL1. Neutrophils comprised a relatively high percentage of leukocytes infiltrating the central nervous system (CNS) early in disease development. G-CSF receptor deficiency and CXCL1 blockade suppressed myeloid cell accumulation in the blood and ameliorated the clinical course of mice that were injected with myelin-reactive Th17 cells. In relapsing MS patients, plasma levels of CXCL5, another ELR+ CXC chemokine, were elevated during acute lesion formation. Systemic expression of CXCL1, CXCL5, and neutrophil elastase correlated with measures of MS lesion burden and clinical disability. Based on these results, we advocate that neutrophil-related molecules be further investigated as novel biomarkers and therapeutic targets in MS.
Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease
Authors: Colleen M. Niswender, P. Jeffrey Conn
Journal: The Annual Review of Pharmacology and Toxicology (2010)

The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that participate in the modulation of synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signaling partners. A great deal of progress has been made in determining the mechanisms by which mGluRs are activated, proteins with which they interact, and orthosteric and allosteric ligands that can modulate receptor activity. The widespread expression of mGluRs makes these receptors particularly attractive drug targets, and recent studies continue to validate the therapeutic utility of mGluR ligands in neurological and psychiatric disorders such as Alzheimer's disease, Parkinson's disease, anxiety, depression, and schizophrenia.
Peptic Ulcer and Dyspepsia in the Army
Authors: H. Tidy
Journal: BMJ (1943)

<h3>ABSTRACT:</h3> Riparian buffers prevent sediment and phosphorus (P) from reaching streams but their accumulation in buffers is seldom measured. This study9s objectives were to determine accumulations of sediment and phosphorus in a multi-species riparian buffer and characterize spatial-temporal patterns of phosphorus in soil water and groundwater. The buffer was planted in 2000, below a steep-sloping field in row-crop production under no-tillage management in Iowa9s Loess Hills. Topographic surveys were conducted in 2002, after the buffer was fully established, and again in 2005. Mapped differences in elevation showed sediment accretion was associated with concentrated flow pathways and lateral flow along the buffer-crop margin. About 32% of the buffer9s outer switchgrass (<i>Panicum virgatum</i> L.) zone had sediment accumulations exceeding 4 cm (1.6 in), which totaled 14.5 Mg ha<sup>−1</sup> (over three years) contributing area, or 4.8 Mg ha<sup>−1</sup> yr<sup>−1</sup> (2.1 t ac<sup>−1</sup> yr<sup>−1</sup>). Among five soil plots, total phosphorus in accreted sediment varied from 7 to 55 g m<sup>−2</sup> (0.02 to 0.18 oz ft<sup>−2</sup>) totaling 9.6 kg P ha<sup>−1</sup> (8.5 lb P ac<sup>−1</sup>) contributing area. Phosphorus concentrations in soil water were greatest beneath the switchgrass, compared to the crop and the buffer9s inner vegetation zones (<i>p</i> &lt; 0.05). Concentrations in soil water and groundwater were also greater where sediment accumulated, presumably due to increased infiltration of runoff. Sediment and phosphorus trapping occurred despite no-tillage management on the contributing hillslope and relatively dry conditions during the study. This emphasizes the importance of installing multiple, complementary conservation practices in sensitive environments. Considering seasonal risks of runoff when selecting buffer species and anticipated runoff patterns when designing buffer areas could reduce subsurface phosphorus losses through riparian areas.
Concurrent and Adjuvant Chemotherapy for Nasopharyngeal Carcinoma: A Factorial Study
Authors: Dora L.W. Kwong, Jonathan S.T. Sham, Gordon K.H. Au, Daniel T.T. Chua, Philip W.K. Kwong, Ashley C.K. Cheng, P.M. Wu, Martin W.M. Law, Carol C.H. Kwok, C.C. Yau, K.Y. Wan, Raymond T.T. Chan, Damon D.K. Choy
Journal: Journal of Clinical Oncology (2004)

To study the efficacy of concurrent chemoradiotherapy (CRT) and adjuvant chemotherapy (AC) for nasopharyngeal carcinoma (NPC).Patients with Ho's stage T3 or N2/N3 NPC or neck node > or = 4 cm were eligible. Patients were randomly assigned to have radiotherapy (RT) or CRT with uracil and tegafur and to have AC or no AC after RT/CRT. AC comprised alternating cisplatin, fluorouracil, vincristine, bleomycin, and methotrexate for six cycles. There were four treatment groups: A, RT; B, CRT; C, RT and AC; D, CRT and AC. For CRT versus RT, groups B and D were compared with groups A and C. For AC versus no AC, groups C and D were compared with groups A and B.Three-year failure-free survival (FFS) and overall survival (OS) for CRT versus RT were 69.3% versus 57.8% and 86.5% versus 76.8%, respectively (P =.14 and.06; n = 110 v 109). Distant metastases rate (DMR) was significantly reduced with CRT (14.8% v 29.4%; P =.026). Locoregional failure rates (LRFR) were similar (20% v 27.6%; P =.39). Three-year FFS and OS for AC versus no AC were 62.5% versus 65% and 80.4% versus 83.1%, respectively (P =.83 and.69; n = 111 v 108). DMR and LRFR were not reduced with AC (P =.34 and.15, respectively). Cox model showed CRT to be a favorable prognostic factor for OS (hazard ratio, 0.42; P =.009).An improvement in OS with CRT was observed but did not achieve statistical significance. The improvement seemed to be associated with a significant reduction in DMR. AC did not improve outcome.
Childhood Kidney Outcomes in Relation to Fetal Blood Flow and Kidney Size
Authors: Marjolein N. Kooijman, Hanneke Bakker, Albert J. van der Heijden, Albert Hofman, Oscar H. Franco, Eric A.P. Steegers, H. Rob Taal, Vincent W.V. Jaddoe
Journal: Journal of the American Society of Nephrology (2014)

Impaired fetal abdominal blood flow may lead to smaller kidneys and subsequent impaired kidney function in later life. In a prospective cohort study among 923 pregnant women and their children, we measured fetal growth, kidney volumes, and umbilical and cerebral artery blood flow (median gestational age of 30.3 weeks; 95% range, 28.5-32.7 weeks). We used a higher umbilical/cerebral artery pulsatility index ratio as an indicator of preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs. At a median age of 5.9 years (95% range, 5.7-6.6 years), we measured childhood kidney volumes, creatinine and cystatin C blood levels, microalbuminuria, BP, and eGFR. A preferential fetal blood flow to the upper body parts at the expense of the intra-abdominal organs associated only with a smaller combined kidney volume in childhood. Fetal combined kidney volume positively associated with childhood combined kidney volume and eGFR, and inversely associated with childhood creatinine and cystatin C levels (all P values <0.05), but did not associate with childhood microalbuminuria and BP. Children within the highest tertile of fetal umbilical/cerebral ratio and the lowest tertile of fetal combined kidney volume had the lowest eGFR (difference, -6.36 ml/min per 1.73 m(2); 95% confidence interval, -11.78 to -0.94 compared with children within the middle tertiles). These data suggest that impaired fetal blood to the abdominal organs and smaller fetal kidney size are associated with subclinical changes in kidney outcomes in school-aged children.