tbuckley/cabot-search huggingface dataset:
Pressure Natriuresis in AT2 Receptor–Deficient Mice with L-NAME Hypertension
Authors: Michael Obst, Volkmar Gross, Jürgen Janke, Maren Wellner, Wolfgang Schneider, Friedrich C. Luft
Journal: Journal of the American Society of Nephrology (2003)

AT(2) receptor-disrupted (AT(2) -/-) mice provide a unique opportunity to investigate the cardiovascular and BP-related effects of NO depletion. This study compared the pressure-diuresis-natriuresis relationship in (AT(2) -/-) and wild-type (AT(2) +/+) mice after treating the animals with L-NAME (130 mg/kg body wt per day) for 1 wk. L-NAME increased mean arterial pressure (MAP) more in AT(2) -/- than in AT(2) +/+ mice (118 +/- 2 versus 108 +/- 4 mmHg). This difference occurred even though L-NAME-treated AT(2) +/+ mice had a greater sodium excretion than AT(2) -/- mice (10.9 +/- 0.5 versus 8.0 +/- 1.0 micro mol/h). The pressure-natriuresis relationship in conscious AT(2) -/- mice was shifted rightward compared with controls. RBF was decreased in AT(2) -/- compared with AT(2) +/+ mice. L-NAME decreased RBF in these mice further from 4.08 +/- 0.43 to 2.79 +/- 0.15 ml/min per g of kidney wt. GFR was not significantly different between AT(2) +/+ and AT(2) -/- mice (1.09 +/- 0.08 versus 1.21 +/- 0.09 ml/min per g of kidney wt). L-NAME reduced GFR in AT(2) -/- to 0.87 +/- 0.07 ml/min per g of kidney wt. Fractional sodium (FE(Na)) and water (FE(H2O)) curves were shifted more strongly to the right by L-NAME in AT(2) -/- mice than in AT(2) +/+ mice. AT(1) receptor blocker treatment lowered BP in both L-NAME-treated strains to basal values. It is concluded that the AT(1) receptor plays a key role in the impaired renal sodium and water excretion induced by NO synthesis blockade. Changes in RBF, GFR, and tubular sodium and water reabsorption are involved and may be also responsible for the greater BP increase in L-NAME-treated AT(2) -/- mice.
Prevention of early variceal rebleeding adding banding to terlipressin therapy
Authors: F. Salerno, M. Cazzaniga
Journal: Gut (2009)

1 month, with a mean period of 38 days in this series, and reaching 74 days in a recent series. 1 13 Surgical series have suggested that postponing surgery until 30 days or more after the onset of the acute pancreatitis is associated with an improved outcome.However, since TENAP is a minimally invasive procedure, this delay could be reduced, patients being only treated on the basis of uncontrolled superinfection of noncollected pancreatic necrosis.In conclusion, transluminal endoscopic necrosectomy is a new step in the field of therapeutic endoscopy; in fact, it is the first application of NOTES and the best assessed in humans.With the results of all the published series, the procedure is becoming more and more standardised and the indications are better known.Since the learning curve of this procedure is unknown and the morbidity is sometimes severe in patients with poor general condition, transluminal endoscopic necrosectomy should only be performed in centres having both experience and expertise in therapeutic endoscopy and in the management of severe acute pancreatitis.
Efficacy of Pitavastatin, a New HMG-CoA Reductase Inhibitor, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes
Authors: Toshihide Kawai, Mikiya Tokui, Osamu Funae, Shu Meguro, Satoru Yamada, Mitsuhisa Tabata, Akira Shimada
Journal: Diabetes Care (2005)

Type 2 diabetes is one of the risk factors for macrovascular disease. Treatment of hypercholesterolemia is important in patients with type 2 diabetes to prevent macrovascular disease. The 3-hydroxy-3-methyl glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are key drugs to lower the cholesterol level not only in nondiabetic patients but also in patients with type 2 diabetes. However, some statins might worsen glycemic control (1) whereas some of them might be neutral (2) or improve glycemic control (3), and their effects on glucose metabolism are controversial. Pitavastatin, an HMG-CoA reductase inhibitor, has been available in Japan since 2003 (4) and the Republic of Korea since 2005, and its effect on glucose metabolism in diabetic patients …
Provision of No-Cost, Long-Acting Contraception and Teenage Pregnancy
Authors: Gina M. Secura, Tessa Madden, Colleen McNicholas, Jennifer Mullersman, Christina M. Buckel, Qiuhong Zhao, Jeffrey F. Peipert
Journal: New England Journal of Medicine (2014)

The rate of teenage pregnancy in the United States is higher than in other developed nations. Teenage births result in substantial costs, including public assistance, health care costs, and income losses due to lower educational attainment and reduced earning potential.
A Plasma Humoral Factor of Extrarenal Origin Causing Release of Reninlike Activity in Hypotensive Dogs
Authors: E. De Vito, C. Wilson, R. E. Shipley, R. P. Miller, B. L. Martz
Journal: Circulation Research (1971)

Plasma reninlike activity significantly increased in anesthetized and unanesthetized normal dogs after intravenous injection of plasma from nephrectomized and normal dogs that have been made hypotensive by controlled hemorrhage. The injection of plasma from nephrectomized, nonhypotensive dogs or the in vitro incubation of normal plasma with calculated proportions of plasma from nephrectomized, hypotensive dogs did not produce any changes in plasma renin concentration or angiotensin production. These results suggest the presence of renin-releasing factor of extrarenal origin which is produced and circulated in the plasma of dogs subjected to periods of hypotension by means of controlled hemorrhage. A direct or indirect action of the renin-releasing factor on the kidney in association with or in conjunction with one or more of the other mechanisms that have been hypothesized to explain the control of renin release is not as yet known. An alternative hypothesis should also be considered. It is possible that the renin-releasing factor may he an activator of the conversion of prerenin to renin and of its release from the kidney into the bloodstream. The source and chemical nature of the renin-releasing factor are not as yet known.
Characterization of the ovarian transcriptome through the use of differential analysis of gene expression methodologies
Authors: J. D. Hennebold
Journal: Human Reproduction Update (2004)

Prior to the development of high-throughput methods for the analysis of differential gene expression, genes required for proper ovarian function were identified on a case-by-case basis. Recently, however, several techniques have been developed that enable investigators to study large-scale changes in gene expression under a variety of experimental conditions. The utilization of these methodologies has led to the identification of a number of novel or previously unappreciated genes that are expressed within distinct cell types in the ovary or at specific stages of the ovarian cycle. This review details the recent use of differential analysis strategies in identifying (i) genes that are expressed exclusively or preferentially in the ovary, (ii) genes that are differentially expressed in isolated ovarian cells in response to hormonal stimulation, and (iii) those genes that are expressed at specific stages of the ovarian cycle. The genes identified through the use of these approaches represent potential targets for designing agents capable of regulating ovarian physiology and thus fertility.
Ion mobility spectrometry for the detection of volatile organic compounds in exhaled breath of patients with lung cancer: results of a pilot study
Authors: M Westhoff, P Litterst, L Freitag, W Urfer, S Bader, J-I Baumbach
Journal: Thorax (2009)

<h3>Background:</h3> Analysis of exhaled breath, especially of volatile organic compounds (VOCs), is of increasing interest in the diagnosis of lung cancer. Compared with other methods of breath analysis, ion mobility spectrometry (IMS) offers a tenfold higher detection rate of VOCs. By coupling the ion mobility spectrometer with a multicapillary column as a pre-separation unit, IMS offers the advantage of an immediate twofold separation of VOCs with visualisation in a three-dimensional chromatogram. The total analysis time is about 500 s compared with gas chromatography/mass spectrometry (GC/MS) of about 1 h. It therefore seemed reasonable to test IMS in breath analysis. <h3>Methods:</h3> In a pilot study, 32 patients with lung cancer were subjected to a breath analysis by IMS. Their IMS chromatograms were compared with those of 54 healthy controls. An IMS that was built for special clinical application was used to identify characteristic peaks of VOCs which might be relevant for the diagnosis of lung cancer in exhaled air of 10 ml volume. <h3>Results:</h3> By a combination of 23 peak regions within the IMS chromatogram, patients with lung cancer, including a patient with carcinoma in situ, were classified and differentiated from healthy persons with an error rate of zero. <h3>Conclusion:</h3> Breath analysis by IMS can detect a discriminating combination of VOCs in patients with lung cancer. By pattern recognition without the need for chemical analysis of the underlying VOCs, IMS has the potential to facilitate lung cancer diagnosis.
Impaired Immune Responses and Antigen-Specific Memory CD4+ T Cells in Hemodialysis Patients
Authors: Nicolle Helena Renier Litjens, Martin Huisman, Marinus van den Dorpel, Michiel Gerardus Henricus Betjes
Journal: Journal of the American Society of Nephrology (2008)

Serologic responses to T cell-dependent vaccinations are severely attenuated in patients with ESRD, but the reasons for this is unknown. In this study, a detailed analysis of antigen-specific T cell responses was performed. Patients on hemodialysis and age- and gender-matched healthy control subjects were vaccinated with hepatitis B surface antigen (HBsAg), antigen-specific CD4(+) T cells were monitored at regular intervals with intracellular cytokine staining and proliferation assays. IL-2-and IFN-gamma-producing CD4(+) T cells were identified as either central or effector memory CD4(+) T cells using antibodies directed against CD45RO and the chemokine receptor CCR7. Control subjects mounted a memory T cell response comprising both central and effector memory CD4(+) T cells, with the central memory response occurring 1 wk before the effector memory response. IL-2(+) HBsAg-specific memory CD4(+) T cells were primarily detected within the effector population. Patients with ESRD showed a delayed response of IL-2-and IFN-gamma-producing central memory CD4(+) T cells, but their maximal responses were similar to those of control subjects. In contrast, patients with ESRD produced only 6.3% of the IL-2(+) HBsAg-specific effector memory CD4(+) T cells produced by control subjects (0.5 +/- 0.2 x 10(4)/L versus 8 +/- 3.5 x 10(4)/L; P < 0.001), and this impaired response correlated with antigen-specific T cell proliferation and anti-HBsAg IgG titers. In conclusion, the production of antigen-specific effector memory CD4(+) T cells after vaccination, which is critical to achieve an adequate humoral response, is severely impaired in patients with ESRD.
TCT-262 Comparable low rates of MACE between patients with ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients in the 12-month follow-up of the e-BioMatrix registry
Authors: Mariano Valdes, Keith G. Oldroyd, Ian Menown, Franz Eberli, Imad A. Alhaddad, Marco Roffi, David Hildick-Smith, David G. Iosseliani, Jacques Berland, Franz X. Kleber, Philip Urban
Journal: Journal of the American College of Cardiology (2013)
Clinical and Prognostic Implications of Plasma Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Patients With Hepatocellular Carcinoma
Authors: Ahmed O. Kaseb, Jeffrey S. Morris, Manal M. Hassan, Adnan M. Siddiqui, E Lin, Lianchun Xiao, Eddie K. Abdalla, Jean-Nicolas Vauthey, Thomas A. Aloia, Sunil Krishnan, James L. Abbruzzese
Journal: Journal of Clinical Oncology (2011)

Purpose Cirrhosis and hepatocellular carcinoma (HCC) together form a two-disease state that affects survival of patients with HCC and dictates treatment decisions and prognostic stratification of patients in clinical trials. The study objective was to improve prognostic stratification of patients with HCC. Patients and Methods We prospectively collected plasma samples and baseline clinicopathologic features from 288 new patients with HCC, and plasma insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) levels were tested. We applied Cox regression and log-rank tests to assess association of IGF-1 and VEGF with overall survival (OS), Kaplan-Meier curves to estimate OS, and recursive partitioning to determine optimal cutoff points for IGF-1 and VEGF. Prognostic ability of conventional and molecular Barcelona Clinic Liver Cancer classifications was compared using the c-index. Results Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor OS, with optimal cut points of 26 ng/mL and 450 pg/mL, respectively. The combination of low IGF-1 and high VEGF predicted median OS of 2.7 months compared with 19 months for patients with high IGF-1 and low VEGF (P &lt; .001), further refining the prognostic ability of conventional HCC staging (P &lt; .001). Conclusion Baseline levels of plasma IGF-1 and VEGF correlated significantly with survival in patients with HCC. Integrating IGF-1 and VEGF into HCC staging significantly enhanced prognostic stratification of patients. If validated, these results may prove to be useful in designing strategies to personalize management approaches among these patients.
Relationship of Obstetric Complications and Differences in Size of Brain Structures in Monozygotic Twin Pairs Discordant for Schizophrenia
Authors: Thomas F. McNeil, Elizabeth Cantor-Graae, Daniel R. Weinberger
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The aim of the study was to determine whether a history of obstetric complications and congenital minor physical anomalies are related to differences in the characteristics of brain structures observed within monozygotic twin pairs discordant for schizophrenia. METHOD: The size of the bilateral hippocampi and cerebral ventricles was studied by magnetic resonance imaging in 22 monozygotic twin pairs discordant for schizophrenia. Obstetric complications and minor physical anomalies were independently assessed through parental report and examination, respectively. RESULTS: Compared with the well co-twins, the ill twins consistently had smaller left and right hippocampi as well as larger left lateral ventricles and third ventricles. Relatively small left and right hippocampi were each significantly related to labor-delivery complications and to prolonged labor per se. Relatively large right lateral ventricle size and large total ventricle size were significantly related to labor-delivery complications, prolonged labor, neonatal complications, and total complications for the entire reproductive sequence. In contrast, these brain size differences were not significantly associated with pregnancy complications or minor physical anomalies. CONCLUSIONS: Trauma at the time of labor and delivery and especially prolonged labor appear to be of importance for brain structure anomalies associated with schizophrenia.
Prediction of Head-Up Tilt Test Result by Analysis of Early Heart Rate Variations
Authors: Ziad Mallat, Eric Vicaut, Adama Sangaré, Jordanka Verschueren, Guy Fontaine, Robert Frank
Journal: Circulation (1997)

Background Head-up tilt testing is a useful test for investigating vasovagal syncope. The determination of early, accurate, predictive criteria for a negative result would permit a reduction in the duration of the tilt test. Methods and Results Patients with no drug use and no illnesses other than recurrent unexplained syncope were recruited. In an initial study (110 consecutive patients), we aimed to determine a predictive criterion based on heart rate variations during the first minutes of upright tilting that could distinguish between patients with positive and negative tilt tests (patients with an early continual decrease in heart rate or blood pressure were excluded). Then we tested the predictive value of the established criterion in a second independent sample of patients with unexplained syncope (109 consecutive patients). An early sustained increase in heart rate ≤18 bpm during the first 6 minutes of upright tilting at a 60° angle allowed us to predict negative tilt tests with 100% specificity, 100% positive predictive value, and 88.6% sensitivity. This criterion was validated in the second, prospective arm of the study (96.4% specificity, 98.4% positive predictive value, and 87.3% sensitivity), even with subsequent use of isoproterenol in low doses. Conclusions In patients with no drug use and no illnesses other than recurrent unexplained syncope, a simple clinical criterion identifies patients who will not develop syncope during a prolonged upright tilt.
Effects of negative pressure assisted ventilation on dyspnoeic sensation and breathing pattern
Authors: T Nishino, S Isono, T Ide
Journal: European Respiratory Journal (1998)

Although negative pressure assisted ventilation with an assist-control mode may have a potential therapeutic role in the treatment of severe dyspnoea, the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns have not been examined. We examined the effects of negative pressure assisted ventilation with the assist-control mode on dyspnoea and breathing patterns produced by a combination of resistive loading and hypercapnia in nine healthy subjects breathing spontaneously. Subjects were asked to rate their sensation of respiratory discomfort using a visual analogue scale. Negative pressure assisted ventilation caused a significant reduction in sensation of respiratory discomfort from a visual analogue scale score of 74 (55-91) (median (range)) before negative pressure assisted ventilation to 34 (15-53) during negative pressure assisted ventilation (p&lt;0.01). During negative pressure assisted ventilation, there were significant changes in breathing patterns characterized by an increase in tidal volume and a decrease in respiratory frequency, while neither minute ventilation nor end-tidal carbon dioxide tension changed. Our results indicate that negative pressure assisted ventilation with the assist-control mode is effective in relief of dyspnoea and that negative pressure assisted ventilation influences the control of breathing to minimize respiratory discomfort.
Partial Target Organ Resistance to Thyroid Hormone
Authors: Hans Henning Bode, Marco Danon, Bruce D. Weintraub, Farahe Maloof, John D. Crawford
Journal: Journal of Clinical Investigation (1973)

An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroid hormone levels (thyroxine [T(4)] 19.5 mug per 100 ml, free T(4) 4 ng per 100 ml, triiodothyronine [T(3)] 505 ng per 100 ml) was studied. He had measurable serum thyroid-stimulating hormone (TSH) levels (average 5.5 muU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings.Methimazole, 50 mg daily, depressed thyroxine synthesis (T(4) 10.5, free T(4) 2.5) and caused a rise in TSH to 11 muU per ml. After discontinuation of treatment, TSH declined to 4.2 muU per ml and chemical hyperthyroidism returned (T(4) 21.0 mug per 100 ml, free T(4) 4.2, and total T(3) 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 mug i.v., caused a brisk rise in TSH to 28 muU per ml, with T(4) rising to 28 mug per 100 ml, free T(4) to 5.6, and T(3) to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH in spite of the markedly elevated serum thyroid hormone levels also suggested that the pituitary was insensitive to suppression by T(3) or T(4). Serum dilution studies gave immunochemical evidence that this patient's TSH was normal. Neither propranolol, 60 mg, chlorpromazine, 30 mg, nor prednisone, 15 mg daily, influenced thyroid indices. Steroid treatment, however, suppressed the pituitary response to TRH, T(3) in doses increased over a period of 12 days to as much as 150 mug daily caused a rise in serum T(3) to above 800 ng per 100 ml, a decline of T(4) to euthyroid levels (T(4) 9.5 mug per 100 ml, free T(4) 1.6 ng per 100 ml), suppression of the RAI uptake from 68% to 35%, and marked blunting of the responses to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone.
Nephropathies and exposure to perchloroethylene in dry-cleaners
Authors: A. Mutti, R. Alinovi, E. Bergamaschi, C. Biagini, S. Cavazzini, I. Franchini, R.R. Lauwerys, A.M. Bernard, H. Roels, E. Gelpi, J. Roselló, I. Ramis, R.G. Price, S.A. Taylor, M. De Broe, G.D. Nuyts, H. Stolte, L.M. Fels, C. Herbort
Journal: The Lancet (1992)
CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells
Authors: Xiuli Wang, ChingLam W. Wong, Ryan Urak, Armen Mardiros, Lihua E. Budde, Wen-Chung Chang, Sandra H. Thomas, Christine E. Brown, Corinna La Rosa, Don J. Diamond, Michael C. Jensen, Ryotaro Nakamura, John A. Zaia, Stephen J. Forman
Journal: Clinical Cancer Research (2015)

T cells engineered with chimeric antigen receptors (CAR) recognizing CD19 can induce complete remission of B-cell malignancies in clinical trials; however, in some disease settings, CAR therapy confers only modest clinical benefit due to attenuated persistence of CAR T cells. The purpose of this study was to enhance persistence and augment the antitumor activity of adoptively transferred CD19CAR T cells by restimulating CAR(+) T cells through an endogenous cytomegalovirus (CMV)-specific T-cell receptor.CMV-specific T cells from CMV seropositive healthy donors were selected after stimulation with pp65 protein and transduced with clinical-grade lentivirus expressing the CD19R:CD28:ζ/EGFRt CAR. The resultant bispecific T cells, targeting CMV and CD19, were expanded via CD19 CAR-mediated signals using CD19-expressing cells.The bispecific T cells proliferated vigorously after engagement with either endogenous CMVpp65 T-cell receptors or engineered CD19 CARs, exhibiting specific cytolytic activity and IFNγ secretion. Upon adoptive transfer into immunodeficient mice bearing human lymphomas, the bispecific T cells exhibited proliferative response and enhanced antitumor activity following CMVpp65 peptide vaccine administration.We have redirected CMV-specific T cells to recognize and lyse tumor cells via CD19CARs, while maintaining their ability to proliferate in response to CMV antigen stimulation. These results illustrate the clinical applications of CMV vaccine to augment the antitumor activity of adoptively transferred CD19CAR T cells in patients with B-cell malignancies.