tbuckley/cabot-search huggingface dataset:
Women, children, and global public health: beyond the millennium development goals
Authors: N. J. Brown, M. P. W. Platt, R. M. Beattie
Journal: BMJ (2015)

As the deadline approaches for the millennium development goals, <b>Nick Brown</b>, <b>Martin Ward Platt</b>, and <b>Mark Beattie</b> discuss the sustainable development goals and the potential barriers to achieving them
Hepatitis B virus antigen-specific T-cell activation in patients with acute and chronic hepatitis B
Authors: M.-C. Jung, U. Spengler, W. Schraut, R. Hoffmann, R. Zachoval, J. Eisenburg, D. Eichenlaub, G. Riethmüller, G. Paumgartner, H.W.L. Ziegler-Heitbrock, H. Will, G.R. Pape
Journal: Journal of Hepatology (1991)
Latent variable models are network models
Authors: Peter C. M. Molenaar
Journal: Behavioral and Brain Sciences (2010)

Cramer et al. present an original and interesting network perspective on comorbidity and contrast this perspective with a more traditional interpretation of comorbidity in terms of latent variable theory. My commentary focuses on the relationship between the two perspectives; that is, it aims to qualify the presumed contrast between interpretations in terms of networks and latent variables.
Preemptive Ganciclovir Therapy To Prevent Cytomegalovirus Disease in Cytomegalovirus Antibody-Positive Renal Transplant Recipients
Authors: Patricia L. Hibberd
Journal: Annals of Internal Medicine (1995)

Objective: To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. Design: Randomized, controlled, multicenter trial. Setting: 6 university-affiliated transplantation centers. Patients: 113 renal transplant recipients who were positive for cytomegalovirus antibody. Intervention: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. Measurements: Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. Results: Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional-hazards model, we found that preemptive ganciclovir still protected against cytomegalovirus disease (adjusted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. Conclusions: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immunosuppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy. *For a listing of the members of the Task Force on Principles for Economic Analysis, see Appendix B.
Abstract 5197: Quantitative phosphorproteomics identified GPER-initiated PKA signal transduction event in breast cancer stem cell
Authors: Alan Chuan-Ying Lai, Yi-Ting Wang, Ruey-Jen Lin, Hsin-Yi Wu, Wen-Wei Chang, Wen-Ying Chang, Yu-Ju Chen, Alice L. Yu
Journal: Cancer Research (2012)

Abstract Human breast cancer stem cells (BCSC) identified recently have the ability to initiate neoplastic growth with differentiation and display higher resistance to chemotherapy and radiotherapy. The allure of targeting this specific group of cells to reduce mortality of disease has attracted research efforts toward BCSC. Although some unique properties of BCSC have been deciphered, the molecular mechanisms are still poorly understood. Here, we applied in-house developed techniques to quantitatively compare the phosphoproteomic profiles between BCSC and non-cancer stem cells (nonCSC) derived from a xenograft of human breast cancer. For quantitative analysis, we utilized a SEMI-strategy for multiplexed label-free quantitation combining pH/acid-controlled IMAC chromatography and LC-MS/MS for relative quantitation of site-specific phosphorylation. This strategy effectively increases the phosphopeptide quantitation coverage. The differentially expressed phosphoproteins were mapped to multiple signaling pathways including NOTCH, CDK/ERK and JAK-STAT pathways, which potentially orchestrate the self renewal and stemness of BCSC. We also demonstrated ∼2 fold greater expression of GPER in BCSC than non-BCSC population, and GPER signaling could induce PKA-mediated phosphorylation of BAD in BCSC. Silencing of GPER via RNAi or mutation of phosphorylation sites of BAD led to reduced proliferation to 40.8 and 53.2 % of control, respectively, and the RNAi silencing of GPER decreased the mammosphere formation of BCSC to 43.5 % of control. These findings implies the importance of GPER and its downstream PKA pathway to the maintenance of stemness characteristics of BCSC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5197. doi:1538-7445.AM2012-5197
Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs.
Authors: M A Martins, S A Shore, N P Gerard, C Gerard, J M Drazen
Journal: Journal of Clinical Investigation (1990)

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril and the neutral endopeptidase (NEP) inhibitors thiorphan and SCH 32615 on the changes in airway opening pressure (PaO) and the recovery of offered peptide were studied after intratracheal administration of substance P (SP) and neurokinin A (NKA) in isolated guinea pig lungs superfused through the trachea. Pao changes and the recovery of offered peptide were significantly greater in NEP inhibitor-treated lungs than in control lungs. Captopril did not cause a significant change in the physiological effects or the recovery of SP and NKA. HPLC analysis of [3H]Pro2,4-SP and 125I-Histidyl1-NKA perfused through the airways showed major cleavage products consistent with NEP action. We conclude that there is significant degradation of both SP and NKA after tracheal infusion of peptides by NEP-like but not by ACE activity; this effect significantly influences the physiological effects of these peptides.
S9 SIFT-MS analysis as a non-invasive determinant of pseudomonas aeruginosa infection in patients with cystic fibrosis
Authors: R Pabary, S Kumar, J Huang, EWFW Alton, A Bush, GB Hanna, JC Davies
Journal: Thorax (2013)

<h3>Background</h3> There is evidence that <i>Pseudomonas aeruginosa </i>(Pa) produces volatile organic compounds (VOCs) such as hydrogen cyanide (HCN) and 2-aminoacetophenone (2-AA). VOCs in exhaled breath are therefore proposed as potential biomarkers of infection. We hypothesised that selective ion-flow mass spectrometry (SIFT-MS) breath analysis might allow discrimination of CF patients with (CF + Pa) and without Pa (CF-Pa). <h3>Methods</h3> 79 adults (31 CF + Pa, 22 CF-Pa and 26 healthy controls) provided starved, single tidal exhalation breath samples into Nalophan<sup>TM</sup> bags. Quantification of 15 VOCs was performed within two hours on SIFT-MS. All results are presented as (median parts-per-billion by volume [IQR]). <h3>Results</h3> 2-AA was significantly higher in CF + Pa than CF-Pa (5.0 [3.4 7.1] vs. 1.3 [0.0 3.2], p &lt;0.01). However, there was significant overlap and median co-efficient of variation was 35.41%; clinical utility is therefore questionable. Dimethyl disulphide was also significantly higher in CF + Pa (95.2 [41.3 211.2 vs. 35.5 [22.1 79.8], p &lt; 0.01). When combined with 2-AA, area under ROC curve was 0.867. Counter to our sputum results, there was no difference in HCN between CF + Pa and CF-Pa (8.1 [5.0 11.9] vs. 6.9 [4.4 11.0], n/s) or between all CF patients and healthy controls (7.8 [4.9 11.5] vs. 7.0 [4.6 11.5], n/s). Our early <i>in vitro</i> data showed decreased butanol above Pa cultures, suggesting consumption. This was replicated in breath with lower levels in CF + Pa vs. CF-Pa (37.4 [24.3 87.6] vs. 91.7 [46.9 143.7], p &lt; 0.05). Of VOCs likely to be of host origin, isoprene was increased in CF vs. controls (108.0 [83.4 195.5] vs. 69.6 [46.9 89], p &lt; 0.01) with no difference between CF + Pa vs. CF-Pa. Acetone was reduced in CF (269.9 [161.9 356.4] vs. 324.9 [236.7 598.9], p &lt; 0.01). <h3>Conclusions</h3> 2-AA is a potential biomarker of Pa infection but clinical applicability is uncertain. Dimethyl disulphide and butanol also show promise. Mouth-exhaled HCN assessed by SIFT-MS does not appear to fulfil its promise as a Pa biomarker. Other VOCs assessed were either similar between Pa groups or different between healthy controls and CF, but unable to differentiate between Pa status. This study provides proof-of-concept for the development of a non-invasive tool with which to screen for lower airway bacterial infection in CF though a clinically applicable test remains some way off.
Clinical Semi-Starvation
Authors: Robert C. Doekel, Clifford W. Zwillich, Charles H. Scoggin, Meir Kryger, John V. Weil
Journal: New England Journal of Medicine (1976)

A decreased metabolic rate has been associated with decreased ventilatory response to hypoxia and hypercapnia, and also with starvation. We fed a 500-calorie carbohydrate diet with supplemental electrolytes, designed to simulate alimentation by usual intravenous fluids, to seven normal subjects for 10 days to determine the effect of semi-starvation on metabolic rate and ventilatory responses. By the 10th day metabolic rate was significantly decreased, and hypoxic ventilatory response decreased to 42 per cent of control (P<0.05). In two subjects, hypoxic ventilatory response was virtually abolished at day 10. These changes reversed toward normal with refeeding. The decrease in hypoxic ventilatory response was significantly (P<0.01) related to the decrease in metabolic rate. Hypercapnic ventilatory response, measured as the slope of the ventilatory response to hypercapnia, decreased slightly but not significantly. The decrease in hypoxic ventilatory response seen during semi-starvation may contribute to the hypoxemia and respiratory failure subsequent to caloric restriction. (N Engl J Med 295:358–361, 1976)
Benchmarking and the percentile assessment of RA: adding a new dimension to rheumatic disease measurement
Authors: F WOLFE
Journal: Annals of the Rheumatic Diseases (2001)

It is somewhat surprising that the importance of benchmarking1 was not generally realised until the last decade.2-5 Benchmarking conveys extraordinary advantages in the understanding of clinical trials, observational studies, and ordinary clinic patients by providing guidelines of expected values. Benchmarks allow us to assess the status of patients, whereas most clinical trials are concerned only with change. Status tells us how patients are doing today and predicts short and long term outcomes, including costs, work disability, and death. Change describes treatment efficacy, but has little to do with prediction or outcome. In the long run, it is status not change that is important.

Benchmarking requires a relevant, generalisable, large, well characterised population sample that is representative of either a population based or a clinical based cohort of patients with rheumatoid arthritis (RA). In the former instance, milder cases and cases not currently meeting RA may be included. The clinical sample should be composed of cases typical of those found in clinical practice, and should be representative of clinical practice in general. In addition, the sample must have enough detail to ensure that relevant RA covariates are captured. Duration of disease can be important for outcomes such as work disability, and mortality can be directly pegged to disease duration. Finally, to be useful the sample must be large enough so that there can be confidence that the estimates are reliable.

Benchmarking also requires accurate and reliable measures, of which there are now a wide range that are relevant to rheumatology …
Mechanisms of entrainment of human common flutter studied with multiple endocardial recordings.
Authors: F G Cosío, M López Gil, F Arribas, J Palacios, A Goicolea, A Núñez
Journal: Circulation (1994)

BACKGROUND The mechanisms of common atrial flutter entrainment have not been directly studied in humans. METHODS AND RESULTS Endocardial mapping in six cases of common flutter showed large right atrial (RA) reentry circuits. Activation was craniocaudal in the anterolateral right atrium and caudocranial in the septum. The inferior vena cava-tricuspid isthmus (IVC-TV) closed the circuit. The high right atrium was paced at progressively shorter cycle lengths (CLs) in all, and the IVC-TV was paced in three cases. We recorded six to eight simultaneous RA electrograms from septum and anterior wall. Transient entrainment was recognized from all sites by capture of all electrograms at two or more paced CLs, with total or partial preservation of baseline flutter sequence and return to baseline after pacing. Antidromic circuit penetration was documented in five cases during high RA pacing and in one with IVC-TV pacing. Short CLs induced orthodromic conduction delays that resulted in a postpacing pause longer than basal flutter CL. ECG fusion with high RA pacing correlated poorly with antidromic septal penetration. This was related to overlap of orthodromic septal activation with anterior wall activation of the following cycle. Pacing disorganized flutter into a brief irregular rapid rhythm in two cases and atrial fibrillation in one case. In two cases, complete antidromic septal penetration led to sudden flutter interruption, and in another case it led to circuit inversion. CONCLUSIONS Direct recordings confirm orthodromic and antidromic penetration of flutter circuits by high and low RA pacing. Short CLs modify the circuit. Disorganization is the most common mode of flutter interruption.
Combined doppler and phased-array echocardiographic estimation of cardiac output.
Authors: P A Magnin, J A Stewart, S Myers, O von Ramm, J A Kisslo
Journal: Circulation (1981)

The capability of a pulsed Doppler flowmeter combined with a phased-array imaging system to measure volume flow was tested in vitro and in patients undergoing cardiac catheterization. The Doppler-phased-array system (DPA) was used to determine vessel diameter and a superimposed cursor was used to locate the range and angle of the Doppler sample volume. DPA estimates of continuous flow through tubing in a water tank correlated strongly (r = 0.99) with measured flow corresponding to physiologic ranges from 3-12 l/min. For pulsatile flow in a water tank, a correlation of r = 0.86 with measured flow was obtained, whereas DPA estimates of cardiac outputs compared with Fick estimates in the 11 patients produced a correlation of r = 0.83. These data indicate that estimates of cardiac output are possible using the DPA approach.
Calcium is a competitive inhibitor of gentamicin-renal membrane binding interactions and dietary calcium supplementation protects against gentamicin nephrotoxicity.
Authors: H D Humes, M Sastrasinh, J M Weinberg
Journal: Journal of Clinical Investigation (1984)

The divalent cations, Ca++ and Mg++, are known to competitively inhibit a large number of aminoglycoside-membrane interactions, so that Ca++ prevents both the neurotoxic and ototoxic effects of these antibiotics acutely in vitro. Since gentamicin-induced plasma and subcellular membrane damage appear to be critical pathogenetic events in gentamicin nephrotoxicity, Ca++ may play a similar protective role in gentamicin-induced acute renal failure. To test this possibility in vivo, rats (group 2) were given a 4% calcium (in the form of CaCO3) supplemented diet to increase delivery of Ca++ to the kidney and administered single daily subcutaneous injections of gentamicin, 100 mg/kg, for 10 d. Compared with a simultaneously studied group (group 1) of rats receiving identical gentamicin dosages and normal diets, Ca++ supplementation ameliorated gentamicin-induced acute renal failure. After 10 doses of gentamicin, blood-urea nitrogen values in group 1 averaged 213 +/- 15 (SE) and 25 +/- 3 (P less than 0.001) in group 2. The progressive decline in renal excretory function, as measured by BUN, in group 1 animals was accompanied by simultaneous declines in renal cortical mitochondrial function and elevations in renal cortex and mitochondrial Ca++ content, quantitative indices of the degree of renal tubular cell injury. Oral Ca++ loading markedly attenuated these gentamicin-induced derangements. After eight and 10 doses of gentamicin, mitochondria isolated from the renal cortex of group 2 rats had significantly higher rates of respiration supported by pyruvate-malate, succinate and N,N,N',N'-tetramethyl-p-phenyldiamine-ascorbate, higher rates of dinitrophenol-uncoupled respiration and greater acceptor control ratios than those measured in mitochondria isolated from the renal cortex of group 1 animals. Similarly, after 8 and 10 doses, renal cortex and renal cortical mitochondrial Ca++ content of group 2 was significantly lower than values observed in group 1. Thus, dietary calcium supplementation significantly protected against gentamicin-induced renal tubular cell injury and, consequently, gentamicin-induced acute renal failure. The mechanism for this protective effect of Ca++ may relate to the manner in which this polycationic antibiotic interacts with anionic sites, primarily the acidic phospholipids of renal membranes. In this regard, Ca++ was found to be a competitive inhibitor both of 125I-gentamicin binding to renal brush border membranes, the initial site of interaction between gentamicin and renal proximal tubule cells, with a composite inhibition constant (Ki) of 12 mM and of 125I-gentamicin binding to phosphatidic acid, an important membrane acidic phosph
Circadian rhythms of frequency domain measures of heart rate variability in healthy subjects and patients with coronary artery disease. Effects of arousal and upright posture.
Authors: H V Huikuri, M J Niemelä, S Ojala, A Rantala, M J Ikäheimo, K E Airaksinen
Journal: Circulation (1994)

BACKGROUND Altered neural regulation of the cardiovascular system may be an important factor for various manifestations of ischemic heart disease. This research was designed to compare the circadian rhythm of cardiac neural regulation and autonomic responses to arousal and upright posture between patients with uncomplicated coronary artery disease (CAD) and age-matched subjects with no evidence of heart disease. METHODS AND RESULTS Twenty-four-hour heart rate variability (HRV) in the frequency domain was analyzed in 20 male patients (mean age, 52 +/- 7 years) with angiographic evidence of CAD without prior myocardial infarction and in 20 healthy men (mean age, 51 +/- 8 years) with no clinical, echocardiographic, or exercise ECG evidence of heart disease. None of the 24-hour average frequency-domain components of HRV differed significantly between the two groups. Healthy subjects had a significant circadian rhythm of normalized units of high-frequency (HF) power of HRV with higher values during sleep. Normalized units of low-frequency (LF) power and the LF/HF ratio also showed a significant circadian rhythm in healthy subjects, with higher values during the daytime. No significant circadian rhythms in any of the normalized spectral components of HRV were observed in patients with CAD, and the night-day difference in LF/HF ratio was smaller in the patients with CAD than in the healthy subjects (0.5 +/- 1.4 versus 1.8 +/- 0.7, P &lt; .001). Awakening when in the supine position resulted in a significant increase in the LF/HF ratio (P &lt; .01) in the healthy subjects, but no significant changes in HRV were observed after awakening in patients with CAD. Assumption of upright position resulted in a comparable decrease in the components of HRV between the groups. CONCLUSIONS The circadian rhythm of cardiac neural regulation is altered in patients with uncomplicated CAD. Reduced autonomic responses to sleep-wake rhythm suggest that the modulation of cardiac autonomic function by stimuli from the central nervous system is impaired in CAD.
Human Plasma Retinol Transport in Malabsorption.
Authors: Frank Rees Smith
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Human Plasma Retinol Transport in Malabsorption.Frank Rees Smith, M.D., John Lindenbaum, M.D.Frank Rees Smith, M.D.Search for more papers by this author, John Lindenbaum, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-817_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPlasma vitamin A concentrations are widely used to screen for malabsorption. Isolation and characterization of the proteins responsible for plasma vitamin A transport in man—retinol-binding protein and prealbumin—has made it possible to explore the regulation of plasma vitamin A concentration in patients with impaired absorption. Concentrations of retinol-binding protein and prealbumin were measured by immunoassays in 22 adults with malabsorption (postgastrectomy, 5; chronic pancreatitis, 3; celiac sprue, 5; tropical sprue, 4; Zollinger - Ellison syndrome, 2; regional iletis, 1; postileal resection, 2) who had normal hepatic and renal function. During active malabsorption (mean stool fat, 23 g/72 hr; range, 8... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Frank Rees Smith, M.D.; John Lindenbaum, M.D.Affiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 817-818KeywordsAttentionBlood plasmaCeliac diseaseChronic pancreatitisFatsImmunoassaysPlasma proteinsPostgastrectomyProteinsVitamin A ePublished: 1 December 2008 Issue Published: 1 May 1973 PDF downloadLoading ...
Central nervous system systemic lupus erythematosus mimicking progressive multifocal leucoencephalopathy.
Authors: B R Kaye, C M Neuwelt, S S London, S J DeArmond
Journal: Annals of the Rheumatic Diseases (1992)

The case is reported of a patient with central nervous system systemic lupus erythematosus (SLE) with features of progressive multifocal leucoencephalopathy (PML) seen clinically and by magnetic resonance imaging. A brain biopsy sample showed microinfarcts. The use of magnetic resonance imaging and IgG synthesis rates in evaluating central nervous system lupus, the co-occurrence of SLE and PML, and the differentiation of these entities by magnetic resonance imaging and by histology are considered.