tbuckley/cabot-search huggingface dataset:
The Association of Predonation Hypertension with Glomerular Function and Number in Older Living Kidney Donors
Authors: Colin R. Lenihan, Stephan Busque, Geraldine Derby, Kristina Blouch, Bryan D. Myers, Jane C. Tan
Journal: Journal of the American Society of Nephrology (2014)

The effect of preexisting hypertension on living donor nephron number has not been established. In this study, we determined the association between preexisting donor hypertension and glomerular number and volume and assessed the effect of predonation hypertension on postdonation BP, adaptive hyperfiltration, and compensatory glomerular hypertrophy. We enrolled 51 living donors to undergo physiologic, morphometric, and radiologic evaluations before and after kidney donation. To estimate the number of functioning glomeruli (NFG), we divided the whole-kidney ultrafiltration coefficient (Kf) by the single-nephron ultrafiltration coefficient (SNKf). Ten donors were hypertensive before donation. We found that, in donors ages >50 years old, preexisting hypertension was associated with a reduction in NFG. In a comparison of 10 age- and sex-matched hypertensive and normotensive donors, we observed more marked glomerulopenia in hypertensive donors (NFG per kidney, 359,499±128,929 versus 558,239±205,152; P=0.02). Glomerulopenia was associated with a nonsignificant reduction in GFR in the hypertensive group (89±12 versus 95±16 ml/min per 1.73 m(2)). We observed no difference in the corresponding magnitude of postdonation BP, hyperfiltration capacity, or compensatory renocortical hypertrophy between hypertensive and normotensive donors. Nevertheless, we propose that the greater magnitude of glomerulopenia in living kidney donors with preexisting hypertension justifies the need for long-term follow-up studies.
C-Terminal Parathyroid Hormone-Related Protein Increases Vascular Endothelial Growth Factor in Human Osteoblastic Cells
Authors: PEDRO ESBRIT, MARIA VICTORIA ALVAREZ-ARROYO, FERNANDO DE MIGUEL, OLGA MARTIN, MARIA EUGENIA MARTINEZ, CARLOS CARAMELO
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The N-terminal region of parathyroid hormone (PTH) and PTH-related protein (PTHrP) interacts with a common PTH/PTHrP receptor in osteoblasts. These cells synthesize PTHrP, but its role in bone turnover is unclear. Intermittent treatment with N-terminal PTHrP or PTH stimulates bone growth in vivo , possibly by increasing local bone factors. In addition, C-terminal PTHrP (107-139), which does not bind to the PTH/PTHrP receptor, appears to affect bone resorption in vivo and in vitro , although its effect on bone formation in vivo remains controversial. Bone angiogenesis is an often overlooked but critical event in the process of bone remodeling. Recently, PTH (1-34) has been shown to induce gene expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, by osteoblastic cells. However, no data are available on the effect of PTHrP (107-139) on VEGF expression in these cells. Using semiquantitative reverse transcription followed by PCR, we found that PTHrP (107-139), between 10 nM and 1 pM, increased VEGF mRNA in human osteoblastic (hOB) cells from trabecular bone. This effect of this agonist, at 10 nM, was maximal (fivefold for VEGF 165 , and twofold for VEGF 121 , compared to control) within 1 to 4 h. This effect was similar to that induced by PTHrP (1-34) in these cells, as well as in human osteosarcoma MG-63 cells, using Northern blot analysis. Moreover, the effect of both peptides, added together at 100 pM, was not higher than that observed with each peptide alone in hOB cells. The effects of PTHrP (107-139) and that of PTHrP (1-34) were abolished by actinomycin D in hOB cells. In these cells, the protein kinase C inhibitor staurosporine, but not the protein kinase A inhibitor H89, inhibited the increase in VEGF mRNA induced by 10 nM PTHrP (107-139). PTHrP (107-139), at 10 nM, also stimulated cytosolic VEGF immunostaining in hOB cells, and VEGF secretion into the medium conditioned by hOB or MG-63 cells for 24 h, which was (ng/mg protein): 10 ± 1 or 5 ± 3 (control), respectively, and 21 ± 1 or 11 ± 2 (PTHrP [107-139]-stimulated), respectively. Furthermore, medium conditioned by these cells for 24 h in the presence of 10 nM PTHrP (107-139), with or without 10 nM PTHrP (1-34), increased about 30% bovine aortic endothelial cell (BAEC) growth at 48 h. This effect was inhibited by adding a specific anti-VEGF antibody to the BAEC incubation medium. These findings demonstrate that the C-terminal domain of PTHrP induces expression and secretion of VEGF, a main angiogenic factor, in hOB cells and MG-63 cells. This relationship between PTHrP and VEGF has potential implications for both bone vascularization and bone formation, and neoangiogenesis in PTHrP-producing tumors.
Arg462Gln sequence variation in the prostate-cancer-susceptibility gene RNASEL and age of onset of hereditary non-polyposis colorectal cancer: a case-control study
Authors: Stefan Krüger, Ann-Sophie Silber, Christoph Engel, Heike Görgens, Elisabeth Mangold, Constanze Pagenstecher, Elke Holinski-Feder, Magnus von Knebel Doeberitz, Gabriela Moeslein, Wolfgang Dietmaier, Susanne Stemmler, Waltraut Friedl, Josef Rüschoff, Hans K Schackert
Journal: The Lancet Oncology (2005)
Effects of myocardial alpha 1-adrenergic receptor stimulation and blockade on contractility in humans.
Authors: J S Landzberg, J D Parker, D F Gauthier, W S Colucci
Journal: Circulation (1991)

BACKGROUND Although alpha-adrenergic receptors are present in both normal and failing human left ventricular myocardium and mediate a positive inotropic effect in several other species, it is not known whether stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect or contributes to basal contractile state in vivo in humans. METHODS AND RESULTS We studied 15 patients with angiographically normal coronary arteries (seven with normal left ventricular function and eight with left ventricular failure). To avoid the confounding effects of changes in ventricular loading conditions and systemic reflex mechanisms, the alpha-adrenergic receptor-selective antagonist phentolamine and agonist phenylephrine were infused directly into the left main coronary artery, and the change in contractile state was assessed by measuring left ventricular peak (+)dP/dt. Phentolamine alone had no effect on left ventricular contractility. Phenylephrine exerted a concentration-related positive inotropic effect in patients with normal as well as those with failing ventricles. The alpha-adrenergic effect of phenylephrine, defined as the component blocked by phentolamine, was significantly less in patients with ventricular failure (108 +/- 28 mm Hg/sec) than in normal subjects (248 +/- 54 mm Hg/sec; p less than 0.03). CONCLUSIONS Myocardial alpha-adrenergic receptors do not contribute to the maintenance of basal left ventricular contractile state in humans. However, stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect, the magnitude of which may be attenuated in patients with heart failure.
Establishment of the Hermansky Pudlak Mastocyte (HPM) Cell Line Which Has the HPS1 16-Bp Duplication (c.1470_1486dup16)
Authors: Arnold Kirshenbaum, Avanti Desai, Geethani Bandara, Glenn Cruse, Elizabeth Fischer, Alasdair M. Gilfillan, William Gahl, Dean D. Metcalfe
Journal: Journal of Allergy and Clinical Immunology (2013)
Anisotropic Conduction in the Triangle of Koch of Mammalian Hearts: Electrophysiologic and Anatomic Correlations
Authors: Mélèze Hocini, Peter Loh, Siew Y. Ho, Damian Sanchez-Quintana, Bernard Thibault, Jacques M.T. de Bakker, Michiel J. Janse
Journal: Journal of the American College of Cardiology (1998)
Treatment of the Acquired Immunodeficiency Syndrome (AIDS) and AIDS-Related Complex with a Regimen of 3′-Azido-2′,3′-Dideoxythymidine (Azidothymidine or Zidovudine) and Acyclovir
Authors: Antonella Surbone, Robert Yarchoan, Nanette Mcatee, M. Robert Blum, Mary Maha, Jean-Pierre Allain, Rose V. Thomas, Hiroaki Mitsuya, Sandra Nusinoff Lehrman, Michael Leuther, James M. Pluda, Freda K. Jacobsen, Harold A. Kessler, Charles E. Myers, Samuel Broder
Journal: Annals of Internal Medicine (1988)

On the basis of observation that acyclovir potentiates the in-vitro antiviral activity of 3-azido-2',3'-dideoxythymidine (also known as azidothymidine or zidovudine) against human immunodeficiency virus (HIV), we administered a regimen of azidothymidine and acyclovir to eight patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. An oral regimen of 100 mg of azidothymidine and 800 mg of acyclovir every 4 hours was in general well tolerated, with the principal toxicity being megaloblastic erythroid changes. The pharmacokinetics of the two drugs were independent of each other. Six patients received the drug combination for at least 10 weeks; all had increased numbers of T4+ lymphocytes (P = 0.028), and two of three assessable patients had reversal of anergy. Two patients tested positive for serum HIV p24 antigen at entry, but became negative with treatment. Data for this small group suggest that this drug combination can be tolerated in patients with severe HIV infections; this study can be used as a basis for larger studies of this drug combination.
AMINO ACIDS AS A SOURCE OF NITROGEN FOR ALLERGIC INFANTS
Authors: LEWIS WEBB HILL
Journal: JAMA (1941)

It is sometimes necessary to feed infants who are allergic to milk a food containing no milk. The soy bean foods have been and will continue to be of value. Their chief disadvantage is that in some infants they cause large, loose bowel movements and irritated buttocks. While such trouble is not common if the food is cooked in a double boiler for three quarters of an hour, it would be of advantage to have an alternate food for use when necessary. Shohl, Butler, Blackfan and MacLachlan,<sup>1</sup>using a synthetic protein-free food<sup>2</sup>in which amino acids prepared from hydrolyzed casein were the chief source of nitrogen, showed that for short periods nitrogen equilibrium and good gains in weight could be maintained. This is of great theoretical interest but of less practical importance unless it can be shown that such a food is adequate for nutrition over relatively long
Who and what should we rely on in early diagnosis of idiopathic pulmonary fibrosis?
Authors: Xiaoqian Chen, Xiaoju Zhang, Xiu Li, Zheng Wang
Journal: European Respiratory Journal (2012)

irreplaceable in the diagnostic approach to lower respiratory tract infections.By contrast, in our study, no information was collected about viral or mixed infection.Viruses may be isolated in up to 45% of severe COPD exacerbations, either alone or together with bacteria, and are likely to be present with fever, but their role in sputum purulence is unclear.
Third consensus on medical treatment of metastatic breast cancer
Authors: S. Beslija, J. Bonneterre, H.J. Burstein, V. Cocquyt, M. Gnant, V. Heinemann, J. Jassem, W.J. Köstler, M. Krainer, S. Menard, T. Petit, L. Petruzelka, K. Possinger, P. Schmid, E. Stadtmauer, M. Stockler, S. Van Belle, C. Vogel, N. Wilcken, C. Wiltschke, C.C. Zielinski, H. Zwierzina
Journal: Annals of Oncology (2009)
A new polymorphism for the RI22H mutation in hereditary pancreatitis
Authors: N Howes
Journal: Gut (2001)

Hereditary pancreatitis (HP) is a rare form of recurrent acute and chronic pancreatitis. Mutations in the cationic trypsinogen (protease serine 1, PRSS1) gene have been identified as causing HP. The R122H (previously known as R117H) mutation is the commonest and can be detected by a single and rapid polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) based technique using the AflIII enzyme. This test however may give a false negative result in the presence of a neutral polymorphism within the enzyme recognition site. The frequency of this event was examined by sequencing studies in patients with HP and in healthy controls.Of 60 families identified by the UK and Ireland consortium of EUROPAC (European Registry for Hereditary Pancreatitis and Familial Pancreatic Cancer), 51 were screened for R122H, N29I, and A16V mutations using standard techniques, and by sequencing of all five exons of cationic trypsinogen.Twelve families had the N29I mutation, one family had A16V and, on standard testing, 15 families had the R122H mutation. An additional family with the R122H mutation was found on direct sequencing. The false negative result was due to a neutral polymorphism C-->T at the third base of the codon, not affecting the amino acid coded for, destroying the AflIII restriction site. This polymorphism was not observed in 50 DNA specimens (100 chromosomes) from controls nor from 50 individuals from PRSS1 mutation negative HP families. A novel mutation specific PCR was developed to avoid this pitfall.One of the 16 families with HP and an R122H mutation contained a polymorphism affecting the AflIII restriction site. Adoption of an alternative R122H assay is important for genetic studies in individuals with apparent HP.
Gastrointestinal Tolerability and Effectiveness of Rofecoxib versus Naproxen in the Treatment of Osteoarthritis
Authors: Jeffrey R. Lisse, Monica Perlman, Gunnar Johansson, James R. Shoemaker, Joy Schechtman, Carol S. Skalky, Mary E. Dixon, Adam B. Polis, Arthur J. Mollen, Gregory P. Geba
Journal: Annals of Internal Medicine (2003)

Background: Gastrointestinal (GI) toxicity mediated by dual cyclooxygenase (COX)-1 and COX-2 inhibition of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause serious alterations of mucosal integrity or, more commonly, intolerable GI symptoms that may necessitate discontinuation of therapy. Unlike NSAIDs, rofecoxib targets only the COX-2 isoform. Objective: To assess the tolerability of rofecoxib compared with naproxen for treatment of osteoarthritis. Design: Randomized, controlled trial. Setting: 600 office and clinical research sites. Patients: 5557 patients (mean age, 63 years) with a baseline diagnosis of osteoarthritis of the knee, hip, hand, or spine. Intervention: Rofecoxib, 25 mg/d, or naproxen, 500 mg twice daily. Use of routine medications, including aspirin, was permitted. Measurements: Discontinuation due to GI adverse events (primary end point) and use of concomitant medication to treat GI symptoms (secondary end point). Efficacy was determined by patient-reported global assessment of disease status and the Australian/Canadian Osteoarthritis Hand Index, as well as discontinuations due to lack of efficacy. Patients were evaluated at baseline and at weeks 6 and 12. Results: Rates of cumulative discontinuation due to GI adverse events were statistically significantly lower in the rofecoxib group than in the naproxen group (5.9% vs. 8.1%; relative risk, 0.74 [95% CI, 0.60 to 0.92]; P = 0.005), as were rates of cumulative use of medication to treat GI symptoms (9.1% vs. 11.2%; relative risk, 0.79 [CI, 0.66 to 0.96]; P = 0.014]). Subgroup analysis of patients who used low-dose aspirin (13%) and those who previously discontinued using arthritis medication because of GI symptoms (15%) demonstrated a relative risk similar to the overall sample for discontinuation due to GI adverse events (relative risk, 0.56 [CI, 0.31 to 1.01] and 0.53 [CI, 0.34 to 0.84], respectively). No statistically significant difference was observed between treatments for efficacy in treating osteoarthritis or for occurrence of other adverse events. Conclusions: In patients with osteoarthritis treated for 12 weeks, rofecoxib, 25 mg/d, was as effective as naproxen, 500 mg twice daily, but had statistically significantly superior GI tolerability and led to less use of concomitant GI medications. Benefits of rofecoxib in subgroup analyses were consistent with findings in the overall sample. *For members of the ADVANTAGE (Assessment of Differences between Vioxx and Naproxen To Ascertain Gastrointestinal Tolerability and Effectiveness) Study Group, see the Appendix.
Rate-dependent QT shortening mechanism for the LQT3 ΔKPQ mutant
Authors: T Nagatomo
Journal: Cardiovascular Research (2002)

Objective: For the congenital long QT (LQT) syndrome involving mutations of the cardiac sodium channel gene SCN5A, LQT3, the initiation of sudden cardiac death tends to be bradycardia- or pause-dependent, contrary to other LQT syndromes that tend to be adrenergic dependent. Enhanced shortening of the prolonged QT interval with increased heart rate has been reported in LQT3 patients. We hypothesized that the rate-dependent shortening of the QT interval may be attributed to the kinetic properties of inactivation the late sodium current (INa) in LQT3. Methods: The ΔKPQ mutant of the human heart voltage-gated sodium channel α-subunit was stably transfected into a mammalian cell line (HEK293). INa was recorded using a whole-cell patch-clamp technique. Results: A train of 50 depolarizing pulses or a train of 50 ventricular action potential waveforms was applied with different interpulse durations. Peak INa for the 50th pulse compared with that of INa in the first pulse was decreased <2% for interpulse durations as short as 20 ms, but late INa amplitude measured at the end of the pulse was decreased 95, 78, 68, 56 and 47% with 1000, 500, 200, 100, 20 ms interpulse intervals, respectively. Using the action potential waveform a similar rate-dependent reduction of late INa was found with minimal reduction of peak INa. Conclusions: Late INa amplitude in the ΔKPQ mutation is strongly rate dependent. Rate-dependent reductions of late INa may cause shortening the QT interval at higher rates. This provides a mechanism correlating the genotype with the clinical phenotype, and provides a rationale for the effectiveness of pacemaker therapy in LQT3 patients.
Sleep-disordered breathing (SDB) and obstructive sleep apnea (OSA) in elderly population with high and low BMI
Authors: Ginevra Del Giudice, Antonello Colangeli, Paolo Carducci, Marina Carunchio, Roberta Di Crecchio, Alfeo Fiore-Donati
Journal: European Respiratory Journal (2011)

Background: SDB has a high prevalence in the elderly population.OSA has been recognized in 7-18% of elderly people.

Aim: Evaluate clinical and sleep characteristics of OSA in a group of elderly patients with SDB according to BMI.

Methods: 47 patients (34M,13F) over 70 yrs old with SDB divided in 2 groups according to BMI (  than 25.0). SDB are studied by means of cardiorespiratory polygraphy. Descriptive statistics were calculated for all variables. Statistical analyses were performed using S-Plus.

Results: 19 patients with BMI  24.9 (group B). The group A (Mean age 75,6±4,2. BMI 23,6. SaO2 92,7±1,9%) reported more difficulty falling asleep (p<0.001) and more daytime sleepines (p=0.0014); AH index were 18,3±1,4 with prevalence of obstructive events as well as group B (AH index 17,6±1,5).Time in bed was 258,6±60,0 min and in group A. Group B (74,9±3,9 mean age. BMI 35,2±5. SaO2 90,7±5,0) had AH index and mean hypopnea duration (27,5±1,1 vs 38,6±4,2) lower than group A. Group B had no longer time in bed (286,2±76,2 min) than other group. Single regression analysis were performed by age related to time in bed, hypopnea duration and apnea duration and was statistically significant only in group A according to time to bed and age (p=.035).

Conclusion: OSA in elderly patients is underdiagnosed. Atypical presentation in elderly patients are common. Low BMI in elderly not excluded OSA risk. We emphasized the need for adjusting the OSA criteria in elderly persons to avoid interpreting OSA symptoms attributable to other diseases more common in old patients.
<i>CFTR</i>,<i>SPINK1</i>,<i>CTRC</i>and<i>PRSS1</i>variants in chronic pancreatitis: is the role of mutated<i>CFTR</i>overestimated?
Authors: Jonas Rosendahl, Olfert Landt, Jana Bernadova, Peter Kovacs, Niels Teich, Hans Bödeker, Volker Keim, Claudia Ruffert, Joachim Mössner, Andreas Kage, Michael Stumvoll, David Groneberg, Renate Krüger, Werner Luck, Matthias Treiber, Michael Becker, Heiko Witt
Journal: Gut (2012)

<h3>Objective</h3> In chronic pancreatitis (CP), alterations in several genes have so far been described, but only small cohorts have been extensively investigated for all predisposing genes. <h3>Design</h3> 660 patients with idiopathic or hereditary CP and up to 1758 controls were enrolled. <i>PRSS1</i>, <i>SPINK1</i> and <i>CTRC</i> were analysed by DNA sequencing, and cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) by melting curve analysis. <h3>Results</h3> Frequencies of <i>CFTR</i> variants p.R75Q, p.I148T, <i>5T</i>-allele and p.E528E were comparable in patients and controls. We identified 103 <i>CFTR</i> variants, which represents a 2.7-fold risk increase (p&lt;0.0001). Severe cystic fibrosis (CF)-causing variants increased the risk of developing CP 2.9-fold, and mild CF-causing variants 4.5-fold (p&lt;0.0001 for both). Combined CF-causing variants increased CP risk 3.4-fold (p&lt;0.0001), while non-CF-causing variants displayed a 1.5-fold over-representation in patients (p=0.14). <i>CFTR</i> compound heterozygous status with variant classes CF-causing severe and mild represented an OR of 16.1 (p&lt;0.0001). Notably, only 9/660 (1.4%) patients were compound heterozygotes in this category. Trans-heterozygosity increased CP risk, with an OR of 38.7, with 43/660 (6.5%) patients and 3/1667 (0.2%) controls being trans-heterozygous (p&lt;0.0001). <h3>Conclusions</h3> Accumulation of <i>CFTR</i> variants in CP is less pronounced than reported previously, with ORs between 2.7 and 4.5. Only CF-causing variants reached statistical significance. Compound and trans-heterozygosity is an overt risk factor for the development of CP, but the number of <i>CFTR</i> compound heterozygotes in particular is rather low. In summary, the study demonstrates the complexity of genetic interactions in CP and a minor influence of <i>CFTR</i> alterations in CP development.
Evidence for Specialized Fibers in the Canine Right Atrium
Authors: PERRY M. HOGAN, LARRY D. DAVIS
Journal: Circulation Research (1968)

Right atria from excised beating dog hearts were immersed in Tyrode solution with the endocardial surface of the anterior wall exposed. Glass microelectrodes were used to impale fibers in different anatomical areas of this preparation. Fibers with action potentials similar in contour to those of ventricular Purkinje fibers were found along the caval border of the crista terminalis in the area of the posterior internodal tract. The action potential of these fibers (plateau fibers) had a resting potential of -85 to -95 mv, a sharp spiked overshoot, a long plateau phase, and inherent diastolic depolarization. The maximum velocity of the action potential upstroke of plateau fibers was consistently greater than that of simultaneously recorded fibers which lacked a plateau phase (regular fibers). Epinephrine or isoproterenol produced an increase in both rate and magnitude of diastolic depolarization of plateau fibers and on occasion converted them to true pacemakers. Acetylcholine accelerated repolarization of plateau fibers with disappearance of the plateau. Increases in extracellular concentration of potassium ions from 2.7 to 10.8 mM rendered regular atrial fibers inexcitable, but plateau fibers continued to show action potentials. Plateau atrial fibers possess several characteristics exhibited by specialized conducting and impulse generating fibers. The possibility that these fibers constitute the posterior internodal tract and function in preferential conduction of excitation to the A-V node was discussed.