tbuckley/cabot-search huggingface dataset:
Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial
Authors: P. D. Brown, S. Pugh, N. N. Laack, J. S. Wefel, D. Khuntia, C. Meyers, A. Choucair, S. Fox, J. H. Suh, D. Roberge, V. Kavadi, S. M. Bentzen, M. P. Mehta, D. Watkins-Bruner
Journal: Neuro-Oncology (2013)

To determine the protective effects of memantine on cognitive function in patients receiving whole-brain radiotherapy (WBRT).Adult patients with brain metastases received WBRT and were randomized to receive placebo or memantine (20 mg/d), within 3 days of initiating radiotherapy for 24 weeks. Serial standardized tests of cognitive function were performed.Of 554 patients who were accrued, 508 were eligible. Grade 3 or 4 toxicities and study compliance were similar in the 2 arms. There was less decline in delayed recall in the memantine arm at 24 weeks (P = .059), but the difference was not statistically significant, possibly because there were only 149 analyzable patients at 24 weeks, resulting in only 35% statistical power. The memantine arm had significantly longer time to cognitive decline (hazard ratio 0.78, 95% confidence interval 0.62-0.99, P = .01); the probability of cognitive function failure at 24 weeks was 53.8% in the memantine arm and 64.9% in the placebo arm. Superior results were seen in the memantine arm for executive function at 8 (P = .008) and 16 weeks (P = .0041) and for processing speed (P = .0137) and delayed recognition (P = .0149) at 24 weeks.Memantine was well tolerated and had a toxicity profile very similar to placebo. Although there was less decline in the primary endpoint of delayed recall at 24 weeks, this lacked statistical significance possibly due to significant patient loss. Overall, patients treated with memantine had better cognitive function over time; specifically, memantine delayed time to cognitive decline and reduced the rate of decline in memory, executive function, and processing speed in patients receiving WBRT. RTOG 0614, ClinicalTrials.gov number CT00566852.
Evaluation of the potential role of chelation therapy in treatment of low to moderate lead exposures.
Authors: J J Chisolm
Journal: Environmental Health Perspectives (1990)

In the overall long-term management of lead poisoning, chelation therapy can have short-term benefits; however, these benefits must be accompanied by drastic reduction in environmental exposure to lead if therapy is to have any long-term benefit. This discussion is limited to calcium disodium ethylenediaminetetraacetate (CaNa2EDTA), the chelating agent that has been the mainstay of treatment of lead poisoning for the past 38 years, and to meso-2,3-dimercaptosuccinic acid (DMSA), a new and promising oral chelating agent, which is an orphan drug and is currently classified as an investigational new drug by the U.S. Food and Drug Administration. With both drugs, multiple courses of treatment will be needed if any substantial reduction in body lead burden is to be achieved. A major limitation of CaNa2EDTA is the enormous diuresis of zinc that it produces. DMSA produces a comparable diuresis of lead, a greater decrease in blood lead, and has negligible influence on the urinary losses of zinc, copper, iron, and calcium. Limited experience to date in man has revealed no significant adverse side effects of DMSA. In animals, DMSA will promptly reduce the concentration of lead in brain and kidney, in particular. By contrast, similar 5-day courses of CaNa2EDTA do not produce any net reduction in brain lead. This is important, as the brain is the critical organ of the adverse effects of lead in children. If the efficacy of DMSA is to be comprehensively evaluated ethically in children, new and more sensitive neurochemical, electrophysiologic, or other markers must be developed.
Tumor Suppressors, Chromosomal Instability, and Hepatitis C Virus–Associated Liver Cancer
Authors: David R. McGivern, Stanley M. Lemon
Journal: Annual Review of Pathology Mechanisms of Disease (2008)

Hepatitis C virus (HCV) is the only known RNA virus with an exclusively cytoplasmic life cycle that is associated with cancer. The mechanisms by which it causes cancer are unclear, but chronic immune-mediated inflammation and associated oxidative chromosomal DNA damage probably play a role. Compelling data suggest that the path to hepatocellular carcinoma in chronic hepatitis C shares some important features with the mechanisms of transformation employed by DNA tumor viruses. Interactions of viral proteins with key regulators of the cell cycle, the retinoblastoma-susceptibility protein, p53, and possibly DDX5 and DDX3 lead to enhanced cellular proliferation and may also compromise multiple cell-cycle checkpoints that maintain genomic integrity, thus setting the stage for carcinogenesis. Dysfunctional DNA damage and mitotic spindle checkpoints resulting from these interactions may promote chromosomal instability and leave the hepatocyte unable to control DNA damage caused by oxidative stress mediated by HCV proteins, alcohol, and immune-mediated inflammation.
Global Hypomethylation Identifies Loci Targeted for Hypermethylation in Head and Neck Cancer
Authors: Graham M. Poage, E. Andres Houseman, Brock C. Christensen, Rondi A. Butler, Michele Avissar-Whiting, Michael D. McClean, Tim Waterboer, Michael Pawlita, Carmen J. Marsit, Karl T. Kelsey
Journal: Clinical Cancer Research (2011)

Abstract Purpose: The human epigenome is profoundly altered in cancers, with a characteristic loss of methylation in repetitive regions and concomitant accumulation of gene promoter methylation. The degree to which these processes are coordinated is unclear so we investigated both in head and neck squamous cell carcinomas. Experimental Design: Global methylation was measured using the luminometric methylation assay (LUMA) and pyrosequencing of LINE-1Hs and AluYb8 repetitive elements in a series of 138 tumors. We also measured methylation of more than 27,000 CpG loci with the Illumina HumanMethylation27 Microarray (n = 91). Results: LINE-1 methylation was significantly associated with LUMA and Infinium loci methylation (Spearman's ρ = 0.52/ρ = 0.56, both P &amp;lt; 0.001) but not that of AluYb8. Methylation of LINE-1, AluYb8, and Infinium loci differed by tumor site (each Kruskal–Wallis, P &amp;lt; 0.05). Also, LINE-1 and LUMA methylation were associated with HPV16 E6 serology (each Mann–Whitney, P &amp;lt; 0.05). Comparing LINE-1 methylation to gene-associated methylation, we identified a distinct subset of CpG loci with significant hypermethylation associated with LINE-1 hypomethylation. An investigation of sequence features for these CpG loci revealed that they were significantly less likely to reside in repetitive elements (Gene Set Enrichment Analysis, P &amp;lt; 0.02), enriched in CpG islands (P &amp;lt; 0.001) and were proximal to transcription factor–binding sites (P &amp;lt; 0.05). We validated the top CpG loci that had significant hypermethylation associated with LINE-1 hypomethylation (at EVI2A, IFRD1, KLHL6, and PTPRCAP) by pyrosequencing independent tumors. Conclusions: These data indicate that global hypomethylation and gene-specific methylation processes are associated in a sequence-dependent manner, and that clinical characteristics and exposures leading to HNSCC may be influencing these processes. Clin Cancer Res; 17(11); 3579–89. ©2011 AACR.
Firearm Legislation and Firearm-Related Fatalities in the United States
Authors: Eric W. Fleegler, Lois K. Lee, Michael C. Monuteaux, David Hemenway, Rebekah Mannix
Journal: JAMA Internal Medicine (2013)

<h3>Importance</h3>Over 30 000 people die annually in the United States from injuries caused by firearms. Although most firearm laws are enacted by states, whether the laws are associated with rates of firearm deaths is uncertain.<h3>Objective</h3>To evaluate whether more firearm laws in a state are associated with fewer firearm fatalities.<h3>Design</h3>Using an ecological and cross-sectional method, we retrospectively analyzed all firearm-related deaths reported to the Centers for Disease Control and Prevention Web-based Injury Statistics Query and Reporting System from 2007 through 2010. We used state-level firearm legislation across 5 categories of laws to create a “legislative strength score,” and measured the association of the score with state mortality rates using a clustered Poisson regression. States were divided into quartiles based on their score.<h3>Setting</h3>Fifty US states.<h3>Participants</h3>Populations of all US states.<h3>Main Outcome Measures</h3>The outcome measures were state-level firearm-related fatalities per 100 000 individuals per year overall, for suicide, and for homicide. In various models, we controlled for age, sex, race/ethnicity, poverty, unemployment, college education, population density, nonfirearm violence–related deaths, and household firearm ownership.<h3>Results</h3>Over the 4-year study period, there were 121 084 firearm fatalities. The average state-based firearm fatality rates varied from a high of 17.9 (Louisiana) to a low of 2.9 (Hawaii) per 100 000 individuals per year. Annual firearm legislative strength scores ranged from 0 (Utah) to 24 (Massachusetts) of 28 possible points. States in the highest quartile of legislative strength (scores of ≥9) had a lower overall firearm fatality rate than those in the lowest quartile (scores of ≤2) (absolute rate difference, 6.64 deaths/100 000/y; age-adjusted incident rate ratio [IRR], 0.58; 95% CI, 0.37-0.92). Compared with the quartile of states with the fewest laws, the quartile with the most laws had a lower firearm suicide rate (absolute rate difference, 6.25 deaths/100 000/y; IRR, 0.63; 95% CI, 0.48-0.83) and a lower firearm homicide rate (absolute rate difference, 0.40 deaths/100 000/y; IRR, 0.60; 95% CI, 0.38-0.95).<h3>Conclusions and Relevance</h3>A higher number of firearm laws in a state are associated with a lower rate of firearm fatalities in the state, overall and for suicides and homicides individually. As our study could not determine cause-and-effect relationships, further studies are necessary to define the nature of this association.
Evaluation of peak flow and symptoms only self management plans for control of asthma in general practice.
Authors: I Charlton, G Charlton, J Broomfield, M A Mullee
Journal: BMJ (1990)

OBJECTIVE--To compare a peak flow self management plan for asthma with a symptoms only plan. DESIGN--Randomisation to one of the self management plans and follow up for a year. SETTING--Four partner, rural training practice in Norfolk. SUBJECTS--115 Patients (46 children and 69 adults) with asthma who were having prophylactic treatment for asthma and attending a nurse run asthma clinic. MAIN OUTCOME MEASURES--The number of doctor consultations, courses of oral steroids, and short term nebulised salbutamol treatments and the number of patients who required doctor consultations, courses of oral steroids, and short term nebulised salbutamol. RESULTS--Both self management plans produced significant reductions in the outcome measures but there were no significant differences in the degree of improvement between the groups. The results were similar for children and adults. The proportions of patients requiring a doctor consultation fell from 98% (50/51) to 66% (34/51) in the peak flow group and from 97% (62/64) to 53% (34/64) in the symptoms only group and the proportions requiring oral steroids from 73% (34/46) to 47% (21/46) and 52% (31/60) to 12% (7/60). The median number of doctor consultations was reduced from 8.0 to 2.0 in the peak flow group and from 4.5 to 1.0 in the symptoms only group. CONCLUSIONS--The peak flow meter was not the crucial ingredient in the improved illness of the two groups. Teaching patients the importance of their symptoms and the appropriate action to take when their asthma deteriorates is the key to effective management of asthma. Simply prescribing peak flow meters without a system of self management and regular review will be unlikely to improve patient care.
British Thoracic Society guideline for non-CFbronchiectasis
Authors: M. C. Pasteur, D. Bilton, A. T. Hill
Journal: Thorax (2010)

The diagnosis, investigation and particularly management of bronchiectasis has been largely empirical and the subject of relatively few controlled clinical trials. There are no clear guidelines, although an Australian position statement has been published concerning bronchiectasis in children. The purposes of these guidelines were therefore threefold: (1) to identify relevant studies in non-cystic fibrosis (CF) bronchiectasis; (2) to provide guidelines on management based on published studies where possible or a consensus view; and (3) to identify gaps in our knowledge and identify areas for future study.
IL-23 and allergic airway inflammation
Authors: C. Addy
Journal: Thorax (2010)

This study examines the role of interleukin 23 (IL-23) in airway inflammation in asthma, focusing on the ability of IL-23 to promote inflammation independently of the known IL-17 pathway and via its effect on T helper 2 (Th2) polarisation. These interactions are studied using in vitro and in vivo techniques.

Mice exposed to allergen showed a significant …
Selective accumulation of differentiated CD8<b>+</b> T cells specific for respiratory viruses in the human lung
Authors: Godelieve J. de Bree, Ester M.M. van Leeuwen, Theo A. Out, Henk M. Jansen, René E. Jonkers, René A.W. van Lier
Journal: The Journal of Experimental Medicine (2005)

The lungs are frequently challenged by viruses, and resident CD8(+) T cells likely contribute to the surveillance of these pathogens. To obtain insight into local T cell immunity to respiratory viruses in humans, we determined the specificity, phenotype, and function of lung-residing CD8(+) T cells and peripheral blood CD8(+) T cells in a paired analysis. The lung contained markedly higher frequencies of influenza (FLU)-specific and respiratory syncytial virus (RSV)-specific CD8(+) T cells when compared with the circulation. This contrasted with an equal distribution of cytomegalovirus- and Epstein-Bar virus-specific CD8(+) T cells. Noticeably, a substantial fraction of the lung-residing FLU- and RSV-specific CD8(+) T cells had progressed to a relatively late differentiation phenotype, reflected by low expression of CD28 and CD27. Lung-derived FLU-specific CD8(+) T cells had low activation requirements, as expansion of these cells could be initiated by cognate peptide in the absence of helper cell-derived signals. Thus, the human lung contains high numbers of differentiated FLU- and RSV-specific memory CD8(+) T cells that can readily expand upon reexposure to virus. Resident lung T cells may provide immediate immunological protection against pulmonary virus infections.
A Psychiatric Clerkship for Law Students
Authors: JOHN CLANCY, GENE BRODLAND, SAMUAL FAHR
Journal: American Journal of Psychiatry (1972)

The need for closer liaison between the legal and medical professions in matters pertaining to human behavior led to the introduction of a psychiatric clerkship for selected law students at the University of Iowa. The objectives were to enable the students to become familiar with methods of diagnosis, interviewing techniques, counseling, and working with community agencies. A questionnaire evaluation verified the value of this approach.
Pleural effusion cytokine profiles in HIV/MTB co-infection
Authors: Anil Chuturgoon, Umesh Lalloo, Alisa Phulukdaree, Devapregasan Moodley, Kennedy Nyamande, Aneesh Ambaram
Journal: European Respiratory Journal (2012)

Pleural effusion is a common presentation in HIV/MTB co-infection. During infection, it is composed primarily of an extensive inflammatory cell infiltrate and an as yet poorly characterized cytokine milieu. Previous reports have shown significant expansion of CD4 T cells in pleural compartments of patients with active MTB infection. Both the immune infiltrate, and to a large degree, the pleural cytokine milieu, may augment viral dynamics and as a result, promote HIV replication in co-infected patients. This may have significant implications for clinical management of dually infected patients. To characterize the pleural effluent in HIV/MTB co-infected patients, we used cytokine array-based technology to profile key cytokines. Our data showed significantly elevated levels of IL6 and IFN-γ in pleural fluid from HIV/MTB co-infection compared to MTB alone (MTB/HIV vs MTB; IL6: 90.6pg/ml vs 85.6pg/ml; IFN-γ: 91.9pg/ml vs 85.4pg/ml). This observation may have reflected increases in systemic levels of these cytokines in dually infected patients (IL6: 32.1pg/ml vs 29.5pg/ml; IFN-γ: 7.6pg/ml vs 6.0pg/ml). We noted moderate inhibition of IL4 production in the MTB/HIV cohort (11.8pg/ml vs 13.8pg/ml). Interestingly, we report lower levels of TNF-α in the pleural compartment of co-infected patients (21.0pg/ml) relative to MTB infection alone (33.2pg/ml), despite stable systemic levels of the cytokine among all groups investigated. Taken together, our data suggests that co-infection with HIV may alter Th1/Th2 polarization dynamics at pleural sites. The high level of TNF-α at MTB pleural sites, in the absence of HIV, is suggestive of conventional pro-inflammatory, innate responses usually associated with tuberculosis.
Idiopathic postural hypotension: physiologic observations and report of a new mode of therapy
Authors: Morton A. Diamond, Raymond H. Murray, Phillip G. Schmid
Journal: Journal of Clinical Investigation (1970)

Two patients with severe postural hypotension associated with upper motor neuron and cerebellar impairment (Shy-Drager syndrome) have been studied. Head-up tilt and lower body negative pressure application caused marked falls in arterial pressure; in one patient, paradoxical vasodilatation was observed. Ice application did not increase arterial pressure or calculated forearm vascular resistance. Intravenous atropine in one patient increased heart rate by 18 beats per min, a cardioacceleratory response similar to exhausting recumbent exercise in that patient. 24 hr urinary catecholamine excretion was low, but aldosterone secretory rate was normal in the more severely afflicted patient. A prolonged elevation of plasma renin activity was noted when post-tilt hypertension occurred. When head-up tilt was not followed by this hypertensive period, plasma renin activity response to tilting was normal. Intra-arterial norepinephrine and tyramine both elicited a vasoconstrictor response. Intra-arterial infusions of norepinephrine and tyramine were repeated after administration of the monoamine oxidase inhibitor tranylcypromine. Norepinephrine was potentiated 4.1- and 0.5-fold in the two patients; tyramine was potentiated 3.7-and 1.1-fold in the two patients, respectively. A therapeutic program of tranylcypromine and tyramine (in the form of cheddar cheese) resulted in substantial clinical improvement. It is concluded that in at least some patients with idiopathic postural hypotension, norepinephrine is present in postganglionic sympathetic fibers. A therapeutic program of tyramine and a monoamine oxidase inhibitor may be of value when more conventional modes of therapy fail.
Nebulisers for bronchiectasis
Authors: D. C. Currie
Journal: Thorax (1997)

from scanty to copious. Patients with bronchiectasis have a number of other symptoms ‐ pectorated fluid/mucus by a small amount, similar to the weight of the nebulised solution some are breathless with impaired lung function, usually predominantly an obstructive (only a 25% increase in the expectorated weight compared with physiotherapy alone). Interestventilatory defect, and asthma is frequent with an incidence of 28% (10 of 36) and 39% (nine ingly, nebulised terbutaline also increased the radioaerosol clearance rate in patients with
Features of Gastric Carcinoma With Lymphoid Stroma Associated With Epstein-Barr Virus
Authors: Hyun Lim, Young Soo Park, Jeong Hoon Lee, Da Hye Son, Ji Yong Ahn, Kwi-Sook Choi, Do Hoon Kim, Kee Don Choi, Ho June Song, Gin Hyug Lee, Hwoon-Yong Jung, Jin-Ho Kim, Jeong Hwan Yook, Byung Sik Kim
Journal: Clinical Gastroenterology and Hepatology (2015)
Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment–Specific Transcriptomes
Authors: Jae Wook Lee, Chung-Lin Chou, Mark A. Knepper
Journal: Journal of the American Society of Nephrology (2015)

The function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. Polyadenylated mRNAs were captured by oligo-dT primers and processed into adapter–ligated cDNA libraries that were sequenced using an Illumina platform. Transcriptomes were identified to a median depth of 8261 genes in microdissected renal tubule samples (105 replicates in total) and glomeruli (5 replicates). Manual microdissection allowed a high degree of sample purity, which was evidenced by the observed distributions of well established cell–specific markers. The main product of this work is an extensive database of gene expression along the nephron provided as a publicly accessible webpage (https://helixweb.nih.gov/ESBL/Database/NephronRNAseq/index.html). The data also provide genome-wide maps of alternative exon usage and polyadenylation sites in the kidney. We illustrate the use of the data by profiling transcription factor expression along the renal tubule and mapping metabolic pathways.
Placebo-Controlled Trial of Glycine Added to Clozapine in Schizophrenia
Authors: A. Eden Evins, Sandra M. Fitzgerald, Lara Wine, Roseanne Rosselli, Donald C. Goff
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The purpose of this study was to evaluate the effects of high-dose oral glycine on positive and negative symptoms and cognitive function when added to clozapine in adults with schizophrenia.METHOD: The authors conducted a double-blind, placebo-controlled, parallel-group trial of 60 g/day of glycine added to clozapine for 8 weeks in 30 adults with schizophrenia. Clinical ratings were performed every 2 weeks.RESULTS: Twenty-seven patients completed the trial. Glycine augmentation of clozapine produced no statistically significant change in positive or negative symptoms or cognitive functioning. No subjects showed clinically significant worsening of clinical ratings.CONCLUSIONS: These data, combined with data from previous trials with d-cycloserine and glycine, suggest that agonists at the glycine site may be less effective when combined with clozapine than they are when combined with conventional antipsychotics.