tbuckley/cabot-search huggingface dataset:
Dynamic Contrast-Enhanced Magnetic Resonance Imaging As a Biomarker for Prediction of Radiation-Induced Neurocognitive Dysfunction
Authors: Yue Cao, Christina I. Tsien, Pia C. Sundgren, Vijaya Nagesh, Daniel Normolle, Henry Buchtel, Larry Junck, Theodore S. Lawrence
Journal: Clinical Cancer Research (2009)

To determine whether early assessment of cerebral microvessel injury can predict late neurocognitive dysfunction after brain radiation therapy (RT).Ten patients who underwent partial brain RT participated in a prospective dynamic contrast-enhanced magnetic resonance imaging (MRI) study. Dynamic contrast-enhanced MRI was acquired prior to, at weeks 3 and 6 during, and 1 and 6 months after RT. Neuropsychological tests were done pre-RT and at the post-RT MRI follow-ups. The correlations between early delayed changes in neurocognitive functions and early changes in vascular variables during RT were analyzed.No patients had tumor progression up to 6 months after RT. Vascular volumes and blood-brain barrier (BBB) permeability increased significantly in the high-dose regions during RT by 11% and 52% (P<0.05), respectively, followed by a decrease after RT. Changes in both vascular volume and BBB permeability correlated with the doses accumulated at the time of scans at weeks 3 and 6 during RT and 1 month after RT (P<0.03). Changes in verbal learning scores 6 months after RT were significantly correlated with changes in vascular volumes of left temporal (P<0.02) and frontal lobes (P<0.03), and changes in BBB permeability of left frontal lobes during RT (P<0.007). A similar correlation was found between recall scores and BBB permeability.Our data suggest that the early changes in cerebral vasculature may predict delayed alterations in verbal learning and total recall, which are important components of neurocognitive function. Additional studies are required for validation of these findings.
Treatment of postmenopausal osteoporosis
Authors: Jean-Yves Reginster
Journal: BMJ (2005)

petownership_stats.htm), and many pets are just as important as a family member or friend, sometimes more; for them, the same level of health care is expected.Cost of treatment and subsequent quality of life is an issue for the care of animals and humans.Doctors may not fully appreciate the importance of the relationship between owners and their animals.This may be relevant when, for example, advising immunocompromised patients of any risk from their pets, or considering the implications of taking an elderly pet owner into care in an environment where animals are banned.When advising patients about owning pets, doctors now have to weigh up the risks of developing allergies. 2 The BMJ and the Veterinary Record plan simultaneous publication of theme issues exploring how the two professions can collaborate for mutual benefit.We would like to cover topics such as the investigation and control of infectious diseases; zoonoses; medical and veterinary education; professional regulation; and issues related to pet ownership.The theme issues, to be published in November 2005, will be a mix of papers, debate pieces, editorials, and reviews.We are particularly interested in original research relevant to both disciplines.
Nonendothelial Source of Nitric Oxide in Arterioles But Not in Venules
Authors: Satoshi Kashiwagi, Mayumi Kajimura, Yasunori Yoshimura, Makoto Suematsu
Journal: Circulation Research (2002)

This study aimed to examine topographic distribution of microvascular NO generation in vivo. To this end, nitrosonium ion (NO + )–sensitive diaminofluorescein diacetate was superfused continuously on the rat mesentery and the fluorescence was visualized in the microvessels through laser confocal microfluorography. Two major sites exhibited a time-dependent elevation of the fluorescence: microvascular endothelia and mast cells. As judged by the fluorescence sensitivity to local application of different inhibitors of NO synthase (NOS), NO availability in arteriolar endothelium and mast cells appeared to be maintained mainly by NOS1, whereas that in venular endothelium greatly depends on NOS3. In venules, the magnitude of inhibitory responses elicited by the inhibitors was positively correlated with the density of leukocyte adhesion. NOS inhibitors significantly reduced, but did not eliminate, the NO + -associated fluorescence in arterioles, capillaries, and venules, suggesting alternative sources of NO in circulation for these microvessels. Immunohistochemistry for NOS isozymes revealed that NOS1 occurred not only in nerve fibers innervated to arterioles but also abundantly in mast cells. Laser flow cytometry of peritoneal cells in vitro revealed abundant expression of NOS1 in mast cells. Interestingly, NOS3 occurred in endothelia of capillaries and venules but not in those of distal arterioles with comparable diameters. These results suggest that the arterioles receive NO from nonendothelial origins involving NOS1 present in nerve terminals and mast cells, whereas venules depend on the endothelial NOS as a major source. Furthermore, nonenzymatic sources of NO from circulating reservoirs constitute a notable fraction throughout different classes of microvessels. The full text of this article is available at http://www.circresaha.org.
Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease
Authors: Elena Myasoedova, Cynthia S Crowson, Hilal Maradit Kremers, Veronique L Roger, Patrick D Fitz-Gibbon, Terry M Therneau, Sherine E Gabriel
Journal: Annals of the Rheumatic Diseases (2011)

Objective To examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA). Methods In a population-based RA incident cohort (1987 American College of Rheumatology criteria first met between 1988 and 2007), details were collected of serum lipid measures, erythrocyte sedimentation rates (ESRs), C-reactive protein (CRP) measures and cardiovascular events, including ischaemic heart disease and heart failure. Cox models were used to examine the association of lipids and inflammation with the risk of CVD and mortality, adjusting for age, sex and year of RA incidence. Results The study included 651 patients with RA (mean age 55.8 years, 69% female); 67% were rheumatoid factor positive. ESR was associated with the risk of CVD (HR=1.2 per 10 mm/h increase, 95% CI 1.1 to 1.3). Similar findings, although not statistically significant, were seen with CRP (p=0.07). A significant non-linear association for total cholesterol (TCh) with risk of CVD was found, with 3.3-fold increased risk for TCh &lt;4 mmol/l (95% CI 1.5 to 7.2) and no increased risk of CVD for TCh ≥4 mmol/l (p=0.57). Low low-density lipoprotein cholesterol (LDL &lt;2 mmol/l) was associated with marginally increased risk of CVD (p=0.10); there was no increased risk for LDL ≥2 mmol/l (p=0.76). Conclusion Inflammatory measures (particularly, ESR) are significantly associated with the risk of CVD in RA. Lipids may have paradoxical associations with the risk of CVD in RA, whereby lower TCh and LDL levels are associated with increased cardiovascular risk.
Sodium chloride absorption by the urinary bladder of the winter flounder. A thiazide-sensitive, electrically neutral transport system.
Authors: J B Stokes
Journal: Journal of Clinical Investigation (1984)

The urinary bladder of the winter flounder absorbs NaCl by a process independent of the transepithelial voltage. In contrast to most other epithelia which have a neutral NaCl-absorptive system, the flounder bladder has a high transepithelial resistance. This feature simplifies analysis of the cellular transport system because the rate of ion transfer through the paracellular pathway is rather low. Experiments were designed to distinguish among three possible mechanisms of neutral NaCl absorption: (a) Na/K/2Cl cotransport; (b) parallel Na/H and Cl/OH exchange; (c) and simple NaCl cotransport. A clear interdependency of Na and Cl for net absorption was demonstrated. NaCl absorption was not dependent on mucosal K and was minimally sensitive to loop diuretics. Thus a Na/K/2Cl transport system was unlikely. The mechanism was not parallel exchange as evidenced by insensitivity to amiloride and to 4,4'-diisothiocyano-2,2'-disulfonic stilbene, an inhibitor of anion exchange. In addition, inhibitors of carbonic anhydrase had no effect. Net absorption was almost completely abolished by hydrochlorothiazide (0.1 mM). Its action was rapid, reversible, and effective only from the mucosal surface. Metolazone, a structurally dissimilar diuretic in the benzothiadiazide class had qualitatively similar actions. The mechanism of NaCl absorption in this tissue appears to be a simple interdependent process. Its inhibition by thiazide diuretics appears to be a unique feature. The flounder bladder may be a model for NaCl absorption in the distal renal tubule.
Primary Ciliary Dyskinesia
Authors: Peadar G. Noone, Margaret W. Leigh, Aruna Sannuti, Susan L. Minnix, Johnny L. Carson, Milan Hazucha, Maimoona A. Zariwala, Michael R. Knowles
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. We hypothesized that the major clinical and biologic phenotypic markers of the disease could be evaluated by studying a cohort of subjects suspected of having PCD. Of 110 subjects evaluated, PCD was diagnosed in 78 subjects using a combination of compatible clinical features coupled with tests of ciliary ultrastructure and function. Chronic rhinitis/sinusitis (n = 78; 100%), recurrent otitis media (n = 74; 95%), neonatal respiratory symptoms (n = 57; 73%), and situs inversus (n = 43; 55%) are strong phenotypic markers of the disease. Mucoid Pseudomonas aeruginosa (n = 12; 15%) and nontuberculous mycobacteria (n = 8; 10%) were present in older (> 30 years) patients with PCD. All subjects had defects in ciliary structure, 66% in the outer dynein arm. Nasal nitric oxide production was very low in PCD (nl/minute; 19 +/- 17 vs. 376 +/- 124 in normal control subjects). Rigorous clinical and ciliary phenotyping and measures of nasal nitric oxide are useful for the diagnosis of PCD. An increased awareness of the clinical presentation and diagnostic criteria for PCD will help lead to better diagnosis and care for this orphan disease.
Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis
Authors: Maarten Boers, Arco C Verhoeven, Harry M Markusse, Mart AFJ van de Laar, Rene Westhovens, J Christiaan van Denderen, Derkjen van Zeben, Ben AC Dijkmans, Andre J Peeters, Piet Jacobs, Hans R van den Brink, Hubert JA Schouten, Désirée MFM van der Heijde, Annelies Boonen, Sjef van der Linden
Journal: The Lancet (1997)
Effects of Topically Delivered Benzamil and Amiloride on Nasal Potential Difference in Cystic Fibrosis
Authors: T. HOFMANN, M. J. STUTTS, A. ZIERSCH, C. RÜCKES, W. M. WEBER, M. R. KNOWLES, H. LINDEMANN, R. C. BOUCHER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

The raised nasal transepithelial potential difference (PD) in cystic fibrosis (CF) reflects accelerated active transport of Na+, and is inhibited by topical administration of the Na+ channel blocker, amiloride. The aim of this study was to investigate the dose-effect and time course of topically administered Na+ conductance inhibitors to inhibit nasal PD, including benzamil, an analog of amiloride. We measured the magnitude of drug inhibition of Na+ transport [percent inhibition of baseline PD ( Δ PD%)] and duration of inhibition of PD, defined as the time when drug inhibition of PD had recovered by 50% (effective time = ET50). Amiloride [10− 3 M (n = 16), 3 × 10− 3 M (n = 9), 6 × 10− 3 M (n = 7), 10− 2 M (n = 3)] or benzamil [1.7 × 10− 3 M (n = 7), and 7 × 10− 3 M (n = 5)] were administered to the nasal surface via an aerosol generated by a jet nebulizer and a nasal mask. The concentration-dependent magnitude ( Δ PD%) of inhibition was similar for amiloride and benzamil ( ∼ 67– 77%), whereas the duration of inhibition (ET50) was about two-and-a-half times longer after benzamil administration as compared with equivalent concentrations of amiloride [1.6 ± 0.06 versus 4.5 ± 0.6 h (ET50 ± SEM), at 6–7 × 10− 3 M]. In vitro studies of cultured normal nasal epithelia demonstrated directly that benzamil induced an approximately 2-fold more prolonged inhibition of active Na+ transport than amiloride. These data suggest aerosolized benzamil is a candidate long-duration Na+ channel blocker for CF.
Comparative Population Genomics of the Ejaculate in Humans and the Great Apes
Authors: Jeffrey M. Good, Victor Wiebe, Frank W. Albert, Hernán A. Burbano, Martin Kircher, Richard E. Green, Michel Halbwax, Claudine André, Rebeca Atencia, Anne Fischer, Svante Pääbo
Journal: Molecular Biology and Evolution (2013)

The rapid molecular evolution of reproductive genes is nearly ubiquitous across animals, yet the selective forces and functional targets underlying this divergence remain poorly understood. Humans and closely related species of great apes show strongly divergent mating systems, providing a powerful system to investigate the influence of sperm competition on the evolution of reproductive genes. This is complemented by detailed information on male reproductive biology and unparalleled genomic resources in humans. Here, we have used custom microarrays to capture and sequence 285 genes encoding proteins present in the ejaculate as well as 101 randomly selected control genes in 21 gorillas, 20 chimpanzees, 20 bonobos, and 20 humans. In total, we have generated >25× average genomic coverage per individual for over 1 million target base pairs. Our analyses indicate high levels of evolutionary constraint across much of the ejaculate combined with more rapid evolution of genes involved in immune defense and proteolysis. We do not find evidence for appreciably more positive selection along the lineage leading to bonobos and chimpanzees, although this would be predicted given more intense sperm competition in these species. Rather, the extent of positive and negative selection depended more on the effective population sizes of the species. Thus, general patterns of male reproductive protein evolution among apes and humans depend strongly on gene function but not on inferred differences in the intensity of sperm competition among extant species.
Phase II Clinical Trial of Sorafenib in Metastatic Medullary Thyroid Cancer
Authors: Elaine T. Lam, Matthew D. Ringel, Richard T. Kloos, Thomas W. Prior, Michael V. Knopp, Jiachao Liang, Steffen Sammet, Nathan C. Hall, Paul E. Wakely, Vasyl V. Vasko, Motoyasu Saji, Pamela J. Snyder, Lai Wei, Daria Arbogast, Minden Collamore, John J. Wright, Jeffrey F. Moley, Miguel A. Villalona-Calero, Manisha H. Shah
Journal: Journal of Clinical Oncology (2010)

Purpose Mutations in the RET proto-oncogene and vascular endothelial growth factor receptor (VEGFR) activity are critical in the pathogenesis of medullary thyroid cancer (MTC). Sorafenib, a multikinase inhibitor targeting Ret and VEGFR, showed antitumor activity in preclinical studies of MTC. Patients and Methods In this phase II trial of sorafenib in patients with advanced MTC, the primary end point was objective response. Secondary end points included toxicity assessment and response correlation with tumor markers, functional imaging, and RET mutations. Using a two-stage design, 16 or 25 patients were to be enrolled onto arms A (hereditary) and B (sporadic). Patients received sorafenib 400 mg orally twice daily. Results Of 16 patients treated in arm B, one achieved partial response (PR; 6.3%; 95% CI, 0.2% to 30.2%), 14 had stable disease (SD; 87.5%; 95% CI, 61.7% to 99.5%), and one was nonevaluable. In a post hoc analysis of 10 arm B patients with progressive disease (PD) before study, one patient had PR of 21+ months, four patients had SD ≥ 15 months, four patients had SD ≤ 6 months, and one patient had clinical PD. Median progression-free survival was 17.9 months. Arm A was prematurely terminated because of slow accrual. Common adverse events (AEs) included diarrhea, hand-foot-skin reaction, rash, and hypertension. Although serious AEs were rare, one death was seen. Tumor markers decreased in the majority of patients, and RET mutations were detected in 10 of 12 sporadic MTCs analyzed. Conclusion Sorafenib is reasonably well tolerated, with suggestion of clinical benefit for patients with sporadic MTC. Caution should be taken because of the rare but fatal toxicity potentially associated with sorafenib.
Delayed Childbearing and Risk of Adverse Perinatal Outcome
Authors: Sven Cnattingius, Michele R. Forman, Heinz W. Berendes, Leena Isotalo
Journal: JAMA (1992)

To investigate the effect of advancing maternal age on pregnancy outcome among healthy nulliparous women, after adjustment for demographic characteristics, smoking, history of infertility, and other medical conditions.A population-based cohort study was conducted with prospectively collected data from the Swedish Medical Birth Register.Nulliparous Nordic women (N = 173,715), aged 20 years and above, who delivered single births at Swedish hospitals from 1983 through 1987.Late fetal and early neonatal death rates; rates of very low birth weight (VLBW, less than 1500 g), moderately low birth weight (MLBW, 1500 through 2499 g), very preterm delivery (less than or equal to 32 weeks), moderately preterm delivery (33 through 36 weeks), and small-for-gestational-age (SGA) infants (less than -2 SDs).Compared with women aged 20 to 24 years, women aged 30 to 34 years had significantly higher adjusted odds ratios (ORs) of late fetal deaths (OR = 1.4); VLBW (OR = 1.2); MLBW (OR = 1.4); very preterm birth (OR = 1.2); and SGA infants (OR = 1.4). Among women aged 35 to 39 years, the adjusted OR was significantly higher for VLBW (OR = 1.9); MLBW (OR = 1.7); very preterm birth (OR = 1.7); moderately preterm birth (OR = 1.2); and SGA infants (OR = 1.7). Among women 40 years old and older, the adjusted OR was significantly higher for VLBW (OR = 1.8); MLBW (OR = 2.0); very preterm birth (OR = 1.9); moderately preterm birth (OR = 1.5); and SGA infants (OR = 1.4).Delayed childbearing is associated with an increased risk of poor pregnancy outcomes after adjustment for maternal complications and other risk factors.
Reduced Superior Temporal Gyrus Volume in Young Offspring of Patients With Schizophrenia
Authors: Rajaprabhakaran Rajarethinam, Sarah Sahni, David R. Rosenberg, Macheri S. Keshavan
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The superior temporal gyrus, a heteromodal auditory and language association cortex, has been found to be smaller in patients with schizophrenia than in normal subjects. However, genetic and/or neurodevelopmental underpinnings of superior temporal gyrus alterations are unknown. Nonpsychotic children with greater genetic risk for schizophrenia exhibit language deficits. The authors studied the superior temporal gyrus in nonpsychotic children at risk for schizophrenia. METHOD: Magnetic resonance imaging was used to measure the right and left superior temporal gyrus of 29 young nonpsychotic subjects who had a parent with schizophrenia and 27 age- and sex-matched comparison subjects who had no family psychiatric history. RESULTS: After controlling for age and intracranial volume, the authors found that the volumes of the right and left superior temporal gyrus of the subjects at risk for schizophrenia were significantly smaller than those of the comparison subjects. Comparison subjects, but not at-risk subjects, showed an inverse correlation between age and left superior temporal gyrus volume. CONCLUSIONS: These findings provide new evidence that superior temporal gyrus abnormalities may result from genetically mediated developmental deviance reflecting greater susceptibility to schizophrenia. Further studies and follow-up will lead to greater understanding of the role of the superior temporal gyrus in the premorbid vulnerability to schizophrenia.
Early life exposure to locally-generated PM10 and lung function measurements at school-age
Authors: Marie-Pierre F. Strippoli, Anna Hallberg, Caroline S. Beardsmore, Michael Silverman, Jonathan Grigg, Claudia E. Kuehni
Journal: European Respiratory Journal (2011)

Aim:  Although multiple studies have linked short-term exposure to particulate matter (PM 10 ) with respiratory symptoms and lung function (LF) in children, little is known about effects of early lifetime exposure.   Methods:  In a population-based cohort study (n=4400) we collected information on residential history from birth to early school-age (6-9 yrs) and modelled primary PM 10  exposure throughout childhood using Airviro. We assessed wheeze symptoms by parental questionnaires and performed spirometry in a sample of children aged 9-13 yrs (n=399). We analysed association between early life exposure to PM 10  and LF using linear regressions controlling for a number of confounders and attacks of wheeze at school-age.   Results:  Median (interquartile range) of early life exposure to PM 10  was 1.83 (0.93-2.70) μg/m 3 . Mean (SD) FVC, FEV 1  and MEF 50  were 2.42 (0.44) l, 2.11 (0.39) l and 2.82 (0.73) l/s respectively. After adjustment FVC was lower with higher exposures to PM 10 .We found no significant association with FEV 1  or MEF 50 . When adjusting for number of attacks results were similar.   Conclusions:  Lifetime exposure to primary PM 10  was associated with lower FVC at school-age which might be independent of wheezing disorders. This result is compatible with a chronic effect of air pollution on normal lung function growth, resulting in a restrictive rather than an obstructive pattern.  Funding: SNF 3200B0-122341, Asthma UK 07/048
Stress-Related Cardiomyopathy Syndromes
Authors: Kevin A. Bybee, Abhiram Prasad
Journal: Circulation (2008)

T he relationship between the heart and the brain is complex and integral in the maintenance of normal cardiovascular function.Certain pathological conditions can interfere with the normal brain-heart regulatory mechanisms and result in impaired cardiovascular function.[4][5][6][7][8][9][10][11][12][13][14][15][16] The stress-related cardiomyopathies appear similar in that they seemingly occur during times of enhanced sympathetic tone and may be precipitated in part or entirely by excessive endogenous or exogenous catecholamine stimulation of the myocardium.Although significant clinical overlap exists in those presenting with stress-associated cardiomyopathy, it is unclear whether myocardial adrenergic hyperstimulation is the only pathophysiological mechanism responsible for these syndromes (Tables 1 and2).