tbuckley/cabot-search huggingface dataset:
Heart Rate Recovery Predicts Clinical Worsening in Patients with Pulmonary Arterial Hypertension
Authors: Omar A. Minai, Ravi Gudavalli, Srinivas Mummadi, Xiaobo Liu, Kevin McCarthy, Raed A. Dweik
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Reduced heart rate recovery after exercise is associated with increased mortality in cardiopulmonary diseases.We sought to evaluate the association between heart rate recovery at 1 minute of rest (HRR1) after 6-min walk test (6MW test) and clinical worsening in patients with idiopathic pulmonary arterial hypertension (IPAH).HRR1 was defined as the difference in heart rate at the end of 6MW test and at 1 minute after completion of the 6MW test. Between August 1, 2009 and March 30, 2010, 75 consecutive patients with IPAH underwent 6MW test and were included in the analysis.Compared with patients with HRR1 ≥ 16 (n = 45 [60%]), those with HRR1 less than 16 (n = 30 [40%]) were more likely to have clinical worsening (odds ratio, 9.7; 95% confidence interval [CI], 3-30; P < 0.001) and shorter time to first clinical worsening event (TCW) (6.7 mo vs. 13 mo; P < 0.001) during follow-up. By multivariable analysis, the best predictors of clinical worsening were HRR1 less than 16 (hazard ratio, 5.2; 95% CI, 1.8-14.8; P = 0.002) and mean pulmonary arterial pressure (hazard ratio, 1.04; 95% CI, 1.007-1.08; P = 0.02). Compared with the distance walked during the 6MW test (6MWD), HRR1 less than 16 was a better predictor of clinical worsening (C statistic 0.757 vs. 0.703) and TCW (C index 0.730 vs. 0.696). The addition of HRR1 increased the ability of 6MWD to predict clinical worsening events.HRR1 after 6MW test is a strong predictor of clinical worsening and TCW in patients with IPAH. The addition of HRR1 to 6MWD increases the capacity of 6MWD to predict clinical worsening and TCW in patients with IPAH.
Renovascular Hypertension and Horseshoe Kidney
Authors: Joel G. Golden
Journal: JAMA (1976)

RECENTLY, it has been suggested that a vascular lesion that affects only a portion of one kidney may have etiologic importance.<sup>1</sup>We report a case of hypertension in which regional renal renin elevation and a stenotic lesion of an artery supplying a segment of a solitary horseshoe kidney appeared to be responsible for the observed elevation of blood pressure. To the best of our knowledge, this constellation of clinical, radiologic, and laboratory findings has not been previously reported. <h3>Report of a Case</h3> A 63-year-old man had apparently been well until May 1974, when he experienced a ten-minute episode of dizziness and unsteadiness of gait. Results of neurological examination were normal, but his blood pressure was 220/130 mm Hg. Therapy with hydrochlorothiazide failed to reduce the hypertension satisfactorily. He was admitted to the San Diego Veterans Administration Hospital with a second episode of dizziness, diplopia, and intermittent ataxia. His blood
Biphasic response against aeroallergen in atopic dermatitis showing a switch from an initial TH2 response to a TH1 response in situ: An immunocytochemical study
Authors: T THEPEN, E LANGEVELDWILDSCHUT, I BIHARI, D WICHEN, F REIJSEN, G MUDDE, C BRUIJNZEELKOOMEN
Journal: Journal of Allergy and Clinical Immunology (1996)
Mathematical model of the changes in heart rate elicited by vagal stimulation.
Authors: F Dexter, M N Levy, Y Rudy
Journal: Circulation Research (1989)

We developed a mathematical model of the underlying cellular mechanisms responsible for the changes in sinus cycle length (SCL) elicited by vagal stimulation in intact animals. The model incorporated a stimulation-mediated depletion of the releasable pool of acetylcholine (ACh) in the nerve endings, the in vitro reaction kinetics of acetylcholinesterase, and the electrical activity of a pacemaker cell with six membrane ionic currents. SCL increased linearly with the frequency of simulated vagal stimulation, as it does in animal experiments, because the concentration of ACh in the neuroeffector junction [( ACh]) saturated as the frequency of stimulation was increased and because SCL increased geometrically in response to increases in [ACh]. The dependence of SCL on the timing of vagal stimulation in the cardiac cycle resulted, in part, from the dependence of [ACh] on SCL. Simulated vagal stimulation entrained the sinus node because the rate of activation and inactivation of ACh-activated K+ channels depended only weakly on membrane potential during diastolic depolarization. SCL increased geometrically with [ACh], because 1) during diastolic depolarization, the amplitude of the ACh-activated K+ current was approximately equal to the amplitude of the sum of the other ionic currents, 2) [ACh] was low enough to saturate neither acetylcholinesterase nor the cellular system that activates the ACh-activated K+ channels, 3) the pacemaker cell membrane behaved electrotonically like a capacitor, and 4) the sum of all the ionic currents increased linearly with the amplitude of the ACh-activated K+ current.
Inhibition of Interleukin 1 Receptor/Toll-like Receptor Signaling through the Alternatively Spliced, Short Form of MyD88 Is Due to Its Failure to Recruit IRAK-4
Authors: Kimberly Burns, Sophie Janssens, Brian Brissoni, Natalia Olivos, Rudi Beyaert, Jürg Tschopp
Journal: The Journal of Experimental Medicine (2003)

Toll-like receptors (TLRs) and members of the proinflammatory interleukin 1 receptor (IL-1R) family are dependent on the presence of MyD88 for efficient signal transduction. The bipartite nature of MyD88 (N-terminal death domain [DD] and COOH-terminal Toll/IL-1 receptor [TIR] domain) allows it to link the TIR domain of IL-1R/TLR with the DD of the Ser/Thr kinase termed IL-1R–associated kinase (IRAK)-1. This triggers IRAK-1 phosphorylation and in turn the activation of multiple signaling cascades such as activation of the transcription factor nuclear factor (NF)-κB. In contrast, expression of MyD88 short (MyD88s), an alternatively spliced form of MyD88 that lacks only the short intermediate domain separating the DD and TIR domains, leads to a shutdown of IL-1/lipopolysaccharide-induced NF-κB activation. Here, we provide the molecular explanation for this difference. MyD88 but not MyD88s strongly interacts with IRAK-4, a newly identified kinase essential for IL-1R/TLR signaling. In the presence of MyD88s, IRAK-1 is not phosphorylated and neither activates NF-κB nor is ubiquitinated. Thus, MyD88s acts as a negative regulator of IL-1R/TLR/MyD88-triggered signals, leading to a transcriptionally controlled negative regulation of innate immune responses.
A comparison between ventricular and lumbar cerebrospinal `uid cytology in adult patients with leptomeningeal metastases
Authors: Marc C. Chamberlain, Patty A. Kormanik, Michael J. Glantz
Journal: Neuro-Oncology (2001)

Leptomeningeal metastases (LMs) are common metastatic complications, occurring in at least 5% of patients with disseminated cancer. Cerebrospinal fluid (CSF) cytology remains the standard for diagnosis and assessment of treatment response, but may be inadequate. Our objective was to compare ventricular and lumbar CSF cytology in patients who had cytologically proven LM and were receiving intra-CSF chemotherapy. Sixty patients with LM, positive lumbar CSF cytology documented at diagnosis, limited extent of CNS disease, and no evidence of CSF flow obstruction were treated with a variety of intra-CSF chemotherapies. All patients underwent a single simultaneous ventricular and lumbar CSF sampling (mean volume of CSF per site examined, 10 ml) to assess response to therapy at either 1 or 2 months after treatment initiation. Ventricular CSF cytology was positive in 44 patients (73%), 35 of whom were also positive by lumbar CSF cytology. Lumbar CSF cytology was positive in 45 patients (75%), of which 35 were also positive by ventricular CSF cytology. Samples were negative at both ventricular and lumbar sites in 6 patients (10%). Paired CSF cytologies were discordant in 19 (32%) patients. The lumbar cytology was negative in 9, whereas the ventricular cytology was positive (lumbar false-negative rate of 17%); the ventricular cytology was negative in 10, whereas the lumbar cytology was positive (ventricular false-negative rate of 20%). In the presence of spinal signs or symptoms of LM, the lumbar CSF cytology was more likely to be positive than was the ventricular (odds ratio = 2.86; 95% confidence interval, 0.86-9.56). Conversely, in the presence of cranial signs or symptoms, the ventricular CSF cytology was more likely to be positive than was the lumbar (odds ratio = 2.71; 95% confidence interval, 0.76-9.71). In this cohort of patients, whose LM was documented initially by positive lumbar CSF cytology, ventricular and lumbar CSF samples obtained during treatment had similar false-negative rates, depending on the site of clinical or radiologic disease. This suggests that both lumbar and ventricular sites must be sampled when assessing treatment response. If clinical or radiographic disease is present only at 1 site, then CSF from that site is more likely to be positive than is CSF obtained from the more distant site.
Differential Strengths of Positive Selection Revealed by Hitchhiking Effects at Small Physical Scales in Drosophila melanogaster
Authors: Yuh Chwen G. Lee, Charles H. Langley, David J. Begun
Journal: Molecular Biology and Evolution (2013)

The long time scale of adaptive evolution makes it difficult to directly observe the spread of most beneficial mutations through natural populations. Therefore, inferring attributes of beneficial mutations by studying the genomic signals left by directional selection is an important component of population genetics research. One kind of signal is a trough in nearby neutral genetic variation due to selective fixation of initially rare alleles, a phenomenon known as "genetic hitchhiking." Accumulated evidence suggests that a considerable fraction of substitutions in the Drosophila genome results from positive selection, most of which are expected to have small selection coefficients and influence the population genetics of sites in the immediate vicinity. Using Drosophila melanogaster population genomic data, we found that the heterogeneity in synonymous polymorphism surrounding different categories of coding fixations is readily observable even within 25 bp of focal substitutions, which we interpret as the result of small-scale hitchhiking effects. The strength of natural selection on different sites appears to be quite heterogeneous. Particularly, neighboring fixations that changed amino acid polarities in a way that maintained the overall polarities of a protein were under stronger selection than other categories of fixations. Interestingly, we found that substitutions in slow-evolving genes are associated with stronger hitchhiking effects. This is consistent with the idea that adaptive evolution may involve few substitutions with large effects or many substitutions with small effects. Because our approach only weakly depends on the numbers of recent nonsynonymous substitutions, it can provide a complimentary view to the adaptive evolution inferred by other divergence-based evolutionary genetic methods.
Consistency of Laboratory Monitoring During Initiation of Mineralocorticoid Receptor Antagonist Therapy in Patients With Heart Failure
Authors: Lauren B. Cooper, Bradley G. Hammill, Eric D. Peterson, Bertram Pitt, Matthew L. Maciejewski, Lesley H. Curtis, Adrian F. Hernandez
Journal: JAMA (2015)

Mineralocorticoid receptor antagonists (MRAs) are a cornerstone of heart failure therapy but have a risk of hyperkalemia.Clinical guidelines recommend close monitoring of renal function and electrolyte levels throughout the course of therapy. 1 No large studies have examined whether laboratory monitoring occurs routinely in community practice.Methods | Using the Centers for Medicare & Medicaid Services Virtual Research Data Center to access claims and summary data for beneficiaries from 10 eastern states who were alive and enrolled in fee-for-service Medicare and in the Medicare Part D prescription drug benefit for the entire 2011 calendar year, we analyzed a cohort with prevalent heart failure who newly initiated MRA therapy.We identified patients with prevalent heart failure using the Chronic Conditions Data Warehouse mid-year indicator; we identified incident MRA use by the presence of a Part D claim for eplerenone or spironolactone between May 1 and September 30, 2011, with no such claims between January 1 and April 30, 2011. 2 Outcomes included measurement of serum creatinine and potassium levels before and after MRA initiation, as suggested in guidelines.We defined appropriate testing as a claim for a specific test or laboratory panel including creatinine and potassium within 120 days before initiation, 2 or more measurements during the early postinitiation period (days 1 through 10), and 3 or more measurements during the extended postinitiation period (days 11 through 90).We counted each hospitalization as 1 test during that period.If the initial MRA prescription fill occurred within 3 days after discharge, we considered the patient to have both in-hospital initiation and 1 test during early postinitiation follow-up.We summarized laboratory testing using frequencies with percentages.We used multivariable logistic regression to estimate associations between patient characteristics and laboratory monitoring, adjusting for demographic characteristics and comorbid conditions.We used a 2-sided P < .05 to establish statistical significance and report 95% confidence intervals.We used SAS version 9.3 (SAS Institute Inc) for all analyses.
Ribose metabolism and nucleic acid synthesis in normal and glucose-6-phosphate dehydrogenase-deficient human erythrocytes infected with Plasmodium falciparum.
Authors: E F Roth, R M Ruprecht, S Schulman, J Vanderberg, J A Olson
Journal: Journal of Clinical Investigation (1986)

The metabolism of pentose-phosphate was investigated in Plasmodium falciparum-infected normal and glucose-6-phosphate dehydrogenase (G6PD)-deficient human red blood cells in vitro. 5'-Phosphoribosyl-1-pyrophosphate (PRPP) content of infected normal red blood cells was increased 50-60-fold at the parasite trophozoite growth stage over that of uninfected cells. The PRPP increment in infected G6PD-deficient cells at comparable stage and parasitemia was only 40% of the value in normal infected cells. Red blood cell PRPP synthetase activity did not change during the growth cycle of the parasite and was similar in both normal and G6PD-deficient cells. Reduced glutathione (GSH) content of G6PD-deficient cells under conditions of culture fell to low or undetectable levels. These low levels of GSH were shown to inhibit the function of red blood cell PRPP synthetase, which requires GSH for full activity. Measurements of the incorporation of 1-14C or 6-14C selectively labeled glucose into parasite nucleic acids revealed that in normal infected red cells, approximately 20% of the pentose was produced via the oxidation of glucose-6-phosphate, whereas in infected G6PD-deficient cells (Mediterranean type), none of the pentose was produced via the oxidative pathway. It is concluded that the low level of reduced GSH found in G6PD deficiency and the resultant partial inhibition of PRPP synthetase together with the missing oxidative pathway for ribose phosphate production can account fully for the reduced parasite growth rate in G6PD-deficient red blood cells described previously. Of these two mechanisms, the predominant one is the impaired PRPP synthetase activity due to low GSH levels in enzyme-deficient red blood cells. The contribution to the ribose-phosphate pool by the hexose monophosphate shunt is relatively minor. A co-existing oxidative stress (which is often hypothesized to mediate the destruction of parasitized red blood cells) is not required to explain growth inhibition in this scheme and does not represent the most straight-forward explanation of the data described in this report.
Clinicopathologic Behavior of Gastric Adenocarcinoma in Hispanic Patients: Analysis of a Single Institution's Experience Over 15 Years
Authors: James C. Yao, Jennifer F. Tseng, Samidha Worah, Kenneth R. Hess, Paul F. Mansfield, Christopher H. Crane, Isac I. Schnirer, Satish Reddy, Silvia S. Chiang, Azmeena Najam, Christina Yu, Geoffrey G. Giacco, Keping Xie, Tsung-Teh Wu, Barry W. Feig, Peter W.T. Pisters, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2005)

To determine the clinicopathologic behavior of gastric adenocarcinoma in Hispanics by comparing Hispanic and non-Hispanic patients treated at a single cancer center.Medical records of patients with invasive gastric cancer treated from 1985 to 1999 were reviewed. Diagnoses were pathologically confirmed. Differences in categorical variables were assessed using the chi(2) test. Logistic regression was used for multivariate analyses. Median survival was estimated using the Kaplan-Meier method. Cox proportional hazards modeling was used to assess the impact of covariates.Of 1,897 patients, 301 (15.9%) were Hispanic. Hispanics were significantly younger at diagnosis than non-Hispanic whites (53.1 +/- 14.4 years v 59.4 +/- 12.7 years, respectively; P < .005) or African Americans (57.6 +/- 15.3 years, P < .005). Hispanics were less likely to have proximal gastric cancers compared with whites (38.9% v 59.5%, respectively; P < .005). Hispanics were more likely to have mucinous/signet-ring type histology (42.5%) than whites (27.4%) and African Americans (32.5%; P < .005). Hispanics were more likely to require total gastrectomy (51%) compared with whites (38%), African Americans (38%), and Asians (36%; P = .039). Among patients with metastases at diagnosis, Hispanics were less likely to have liver metastasis than whites (30% v 44%, respectively; P = .009) but more likely to have peritoneal metastasis than whites and African Americans (54% v 41% and 47%, respectively; P = .002). In Cox analyses, Asian race, earlier stage, papillary/tubular histology, distal location, and younger age were favorable predictors of survival.Hispanic ethnicity does not impact survival in gastric adenocarcinoma. However, histology, metastasis pattern, tumor localization, and other clinical parameters differ sufficiently to warrant further investigation into the epidemiology, pathogenesis, and molecular biology of gastric cancer in this population.
Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases
Authors: L Silvia Munoz-Price, Laurent Poirel, Robert A Bonomo, Mitchell J Schwaber, George L Daikos, Martin Cormican, Giuseppe Cornaglia, Javier Garau, Marek Gniadkowski, Mary K Hayden, Karthikeyan Kumarasamy, David M Livermore, Juan J Maya, Patrice Nordmann, Jean B Patel, David L Paterson, Johann Pitout, Maria Virginia Villegas, Hui Wang, Neil Woodford, John P Quinn
Journal: The Lancet Infectious Diseases (2013)
Oral vasopressin receptor antagonist tolvaptan in right heart failure due to pulmonary hypertension
Authors: Yuichi Tamura, Mai Kimura, Makoto Takei, Tomohiko Ono, Masataka Kuwana, Toru Satoh, Keiichi Fukuda, Marc Humbert
Journal: European Respiratory Journal (2015)

During the past decade, the prognosis of patients with pulmonary hypertension (PH) has improved due to the development of pulmonary arterial vasodilators [1]. Yet, treatment for right-sided heart failure (RHF) associated with PH has not improved, despite being the most important prognostic factor for chronic RHF [2, 3]. Existing treatment strategies for RHF associated with PH are restricted to administration of loop diuretics and inotropes [4]; however, administration of high doses of loop diuretics may worsen the outcome of chronic heart failure [5, 6]. In recent years, tolvaptan, an oral, nonpeptide, selective vasopressin V2-receptor antagonist, has been developed for the treatment of hyponatraemia [7], autosomal dominant polycystic kidney disease [8] and heart failure. Used in addition to standard therapy that includes diuretics, tolvaptan improves many signs and symptoms of heart failure without serious adverse events [9]. However, there is no report describing the effect of tolvaptan on RHF, independent of left-sided heart disease. Vasopressin receptor antagonist tolvaptan achieved furosemide reductions and right heart failure improvements in PH <http://ow.ly/Lopej> The authors acknowledge the medical staff of the Dept of Cardiology, Keio University Hospital, Tokyo, Japan, for completion of medical records.
Left Ventricular Hypertrophy as an Independent Predictor of Acute Cerebrovascular Events in Essential Hypertension
Authors: Paolo Verdecchia, Carlo Porcellati, Gianpaolo Reboldi, Roberto Gattobigio, Claudia Borgioni, Thomas A. Pearson, Giuseppe Ambrosio
Journal: Circulation (2001)

It is uncertain whether left ventricular hypertrophy (LVH) confers an increased risk for cerebrovascular disease in apparently healthy patients with essential hypertension.A total of 2363 initially untreated hypertensive patients (mean age 51+/-12 years, 47% women) free of previous cardiovascular disease were followed up for up to 14 years (mean 5 years). At entry, all patients underwent diagnostic tests, including ECG, echocardiography, and 24-hour ambulatory blood pressure (BP) monitoring. At entry, the prevalence of LVH was 17.6% by ECG (Perugia score) and 23.7% by echocardiography (LVM >125 g/m(2)). Over the subsequent years, 105 patients experienced a first stroke or transient ischemic attack. The cerebrovascular event rate was higher among patients with LVH at entry, diagnosed by either ECG or echocardiography, than among those without hypertrophy (both P<0.01). After control for the significant influence of age, sex, diabetes, and 24-hour mean ambulatory BP, LVH by ECG conferred an increased risk for cerebrovascular events (relative risk [RR] 1.79; 95% CI 1.17 to 2.76). LVH by echocardiography also conferred a higher risk for cerebrovascular events (RR 1.64; 95% CI 1.07 to 2.68). For each increase in LV mass of 1 SD (29 g/m(2)), there was a significant independent increase in the risk for cerebrovascular events (RR 1.31; 95% CI 1.09 to 1.58).In apparently healthy patients with essential hypertension, LVH diagnosed by ECG or echocardiography confers an excess risk for stroke and transient ischemic attack independently of BP and other individual risk factors.
Conversion Gastrectomy After Repeated Intravenous and Intraperitoneal Paclitaxel (PTX) Administration with Oral S-1 for Peritoneal Dissemination of Advanced Gastric Cancer with Malignant Ascites
Authors: Kitayama Joji, Ishigami Hironori, Yamaguchi Hironori, Emoto Shigenobu
Journal: Annals of Oncology (2014)