tbuckley/cabot-search huggingface dataset:
S15 An office based advanced driving simulator to assess driving performance in Obstructive Sleep Apnoea Syndrome (OSAS): a pilot study
Authors: D. Ghosh, S. Jamson, M. W. Elliott
Journal: Thorax (2010)

<h3>Introduction</h3> Advising patients with Obstructive Sleep Apnoea Syndrome (OSAS) about whether they are safe to drive is challenging. Driving simulator studies have shown that OSAS patients perform poorly (Hack <i>et al</i>, 2001) but most simulators are simple, not realistic and in particular lack face validity, for example, multiple off road events during a short run. The Institute for Transport Studies, University of Leeds, host the UK9s most sophisticated driving simulator but had also developed a PC based simulator (MiniSim) which incorporates the same realistic graphics and is much closer to ‘proper’ driving than most existing systems. It thus has the potential to be used in everyday clinical practice. We have investigated whether two parameters, proportion of high frequency steering activity (HFS) and standard deviation of lane position (SDLP), previously shown to be impaired in drivers suffering from fatigue, might predict drivers’ behaviour in safety-critical scenarios. <h3>Methods</h3> After a practice run, 63 patients (age 53±10, ESS 11±3, ODI 39±19) completed 50 min motorway driving on the MiniSim. Two situations were programmed that required evasive action to avoid a crash. A ‘fail’ was determined by an outright crash or veering completely out of lane. We compared HFS and SDLP in subjects with ‘pass’ or ‘fail’ and with Oxygen Desaturation Index (ODI) and Epworth Sleepiness Score (ESS). <h3>Results</h3> (Abstract S15 Table 1) ‘Fail’ was more likely with worse sleep disordered breathing, but was not affected by subjective sleepiness. Subjects who ‘failed’ had significantly worse HFS (0.27 vs 0.34, p=0.03) &amp; SDLP (0.58 vs 0.41, p=0.002). Both HFS &amp; SDLP worsened with time. There was also a strong correlation between HFS &amp; SDLP (r=0.51, p&lt;0.0001). <h3>Conclusion</h3> These data show that HFS and SDLP have promise as objective markers of poor driving in OSAS patients. They relate to measures of disease severity and to an event which has face validity as an indicator of poor driving in the real world. The patient will not be aware that they are being measured and therefore they have potential for repeated use.
Severe Anemia in Malawian Children
Authors: Job C.J. Calis, Kamija S. Phiri, E. Brian Faragher, Bernard J. Brabin, Imelda Bates, Luis E. Cuevas, Rob J. de Haan, Ajib I. Phiri, Pelani Malange, Mirriam Khoka, Paul J.M. Hulshof, Lisette van Lieshout, Marcel G.H.M. Beld, Yik Y. Teo, Kirk A. Rockett, Anna Richardson, Dominic P. Kwiatkowski, Malcolm E. Molyneux, Michaël Boele van Hensbroek
Journal: New England Journal of Medicine (2008)

Severe anemia is a major cause of sickness and death in African children, yet the causes of anemia in this population have been inadequately studied.We conducted a case-control study of 381 preschool children with severe anemia (hemoglobin concentration, <5.0 g per deciliter) and 757 preschool children without severe anemia in urban and rural settings in Malawi. Causal factors previously associated with severe anemia were studied. The data were examined by multivariate analysis and structural equation modeling.Bacteremia (adjusted odds ratio, 5.3; 95% confidence interval [CI], 2.6 to 10.9), malaria (adjusted odds ratio, 2.3; 95% CI, 1.6 to 3.3), hookworm (adjusted odds ratio, 4.8; 95% CI, 2.0 to 11.8), human immunodeficiency virus infection (adjusted odds ratio, 2.0; 95% CI, 1.0 to 3.8), the G6PD(-202/-376) genetic disorder (adjusted odds ratio, 2.4; 95% CI, 1.3 to 4.4), vitamin A deficiency (adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.8), and vitamin B12 deficiency (adjusted odds ratio, 2.2; 95% CI, 1.4 to 3.6) were associated with severe anemia. Folate deficiency, sickle cell disease, and laboratory signs of an abnormal inflammatory response were uncommon. Iron deficiency was not prevalent in case patients (adjusted odds ratio, 0.37; 95% CI, 0.22 to 0.60) and was negatively associated with bacteremia. Malaria was associated with severe anemia in the urban site (with seasonal transmission) but not in the rural site (where malaria was holoendemic). Seventy-six percent of hookworm infections were found in children under 2 years of age.There are multiple causes of severe anemia in Malawian preschool children, but folate and iron deficiencies are not prominent among them. Even in the presence of malaria parasites, additional or alternative causes of severe anemia should be considered.
Stabilizing prevalence trends of eczema, asthma and rhinoconjunctivitis in Dutch schoolchildren (2001–2010)
Authors: D. de Korte‐de Boer, M. Mommers, C. M. L. Gielkens‐Sijstermans, H. M. H. Creemers, S. Mujakovic, F. J. M. Feron, O. C. P. van Schayck
Journal: Allergy (2015)

In contrast to many countries, a decrease in childhood wheeze prevalence was previously reported for the Netherlands. In repeated cross-sectional surveys in 2001, 2005 and 2010, we investigated whether this trend continued, and additionally examined prevalence trends of eczema, asthma and rhinoconjunctivitis among 8- to 11-year-old schoolchildren eligible for a routine physical examination. Overall, ~90% participated (mean age: 8.8 years in 2001 and 10.5 years in 2005 and 2010). Eczema, wheeze and asthma prevalence did not change significantly between 2001 and 2010, but rhinoconjunctivitis prevalence increased from 8.4% in 2001 to 12.3% in both 2005 and 2010 (Ptrend < 0.01). In conclusion, after a decrease in wheeze prevalence among Dutch schoolchildren between 1989 and 2001, no further decrease was observed until 2010. Similarly, the prevalence of eczema and asthma remained stable, but rhinoconjunctivitis prevalence increased between 2001 and 2010. The latter may be an effect of older age and not a true increase over time.
Transient neonatal hyperammonemia: Squeezing an iceberg into a pigeon hole
Authors: Yugen Edward Hsia
Journal: Hepatology (1986)

Transient neonatal hyperammonemia (TNH) was reviewed in six cases seen by the authors and in 27 selected from the literature. These 33 cases were compared with 13 infants with urea cycle enzyme deficiencies (UCED). The two groups were similar in sex distribution, routes of delivery, time of onset of seizures, Apgar scores and in the prevalence of perinatal complications. Patients with TNH had significantly lower birth weights (2,282±78 gm vs. 3,336±222; mean±SEM; P &lt; 0.001) and gestational ages (35±0.5 vs. 40±0.5 weeks; p e 0.001). The mean time of onset of respiratory distress (4±1 vs. 72 2 26 hr; P &lt; 0.001), need for ventilatory support (P &lt; 0.001), time of onset of lethargy (P &lt; 0.006) and coma (P &lt; 0.005) all occurred earlier in patients with TNH than in those with UCED. Plasma ammonium concentra- tions were higher in patients with TNH than UCED (1,871±209 vs. 973±169 μ M ;P &lt; 0.02). Respiratory distress occurred in all except one patient with TNH within the first 24 hr, while it occurred in none of the UCED patients within the first 30 hr and only one occurred in 62%of the latter group at any time. The clinical presentations of these two syndromes permit differentiation on clinical grounds alone.
KB-R7943 Prevents Acute, Atrial Fibrillation–Induced Shortening of Atrial Refractoriness in Anesthetized Dogs
Authors: Akira Miyata, Douglas P. Zipes, Stephen Hall, Michael Rubart
Journal: Circulation (2002)

Background— To test the hypothesis that Ca 2+ influx via Na + /Ca 2+ exchange (NCX) underlies atrial fibrillation (AF)–induced shortening of atrial effective refractory period (AERP), we examined the potential of KB-R7943 (KB), a selective inhibitor of Ca 2+ -influx mode NCX, to attenuate this effect. Methods and Results— Studies were performed in 41 isoflurane-anesthetized dogs. In sinus rhythm dogs, peak AERP changes resulting from intravenous KB infusion ranged from (mean±SEM) 4.4±0.4% (1 mg/kg) to 14.8±2.6% (5 mg/kg; ED 50 =1.9 mg/kg). AERP was maximally prolonged between 5 and 10 minutes after beginning of KB infusion and returned to baseline values within 30 minutes thereafter. Rapid atrial pacing–induced AF reversibly shortened AERP ( P &lt;0.001) in 5 dogs, averaging 14.9±2.1% after 90 minutes of AF. Both the time course and magnitude of mean AERP changes in 5 AF dogs receiving 5 mg/kg KB were indistinguishable from those in 5 sinus rhythm dogs receiving an equivalent KB dose ( P &gt;0.05). We measured cardiac tissue and arterial plasma KB concentrations produced by intravenous infusion (1 mg · kg −1 · min −1 ) of 5 mg/kg KB. Plasma drug concentration peaked at the end of KB infusions (30.86±3.26 nmol/L; n=4 dogs) and declined to 0.56±0.19 nmol/L after 100 minutes. The cardiac tissue-to-plasma drug concentration gradient averaged ≈40 at 100 minutes after start of KB infusion. KB at concentrations achieved in vivo irreversibly blocked NCX-mediated Ca 2+ influx in isolated canine right atrial myocytes by ≈60%, but had no significant effect on NCX-dependent Ca 2+ extrusion. Conclusion— NCX-mediated Ca 2+ influx plays an important role in acute, AF-induced AERP shortening.
Mechanism of Suppression of Vasopressin during Alpha-Adrenergic Stimulation with Norepinephrine
Authors: Tomas Berl, Pravit Cadnapaphornchal, Judith A. Harbottle, Robert W. Schrier
Journal: Journal of Clinical Investigation (1974)

Recent studies have demonstrated that the water diuresis associated with intravenous infusion of norepinephrine is mediated primarly by suppression of antidiuretic hormone (ADH) release. To investigate whether the increase in cerebral perfusion pressure with intravenous norepinephrine (0.5 mug/kg/min) is directly responsible for suppression of ADH release, the carotid circulation of dogs was pump-perfused bilaterally to selectively increase cerebral perfusion pressure. In six experiments cerebral perfusion pressure was increased from a mean of 125 to 151 mm Hg and then returned to 120 mm Hg. This maneuver was not associated with a reversible increase in renal water excretion. The possibility was also examined that norepinephrine exerts a direct central effect to suppress ADH release. In 12 experiments norepinephrine was infused into the carotid artery in a subpressor dose (0.12 mug/kg/min) estimated to equal the amount of the catecholamine reaching the cerebral circulation with intravenous norepinephrine. The urinary osmolality (Uosm) was not significantly altered with intracarotid norepinephrine (932 to 959 mosmol/kg H(2)O. The possibility was also examined that changes in autonomic neural tone from arterial baroreceptors is responsible for suppression of ADH release with intravenous norepinephrine. In sham-operated animals intravenous norepinephrine diminished Uosm from 1,034 to 205 mosmol/kg H(2)O (P<0.001) whereas in animals with denervated arterial baroreceptors intravenous norepinephrine was not associated with a significant alteration in Uosm (1,233 to 1,232 mosmol/kg) H(2)O. These different effects on urinary osmolality occurred in the absence of differences in plasma osmolality and volume status. The results therefore indicate that norepinephrine primarily suppresses ADH release by altering autonomic baroreceptor tone rather than by a direct central or pressor effect of the catecholamine. This same mechanism may be the primary pathway for other nonosmotic influences on ADH release.
Decline of Natural Killer Cell Activity in Sublethally Irradiated Mice2
Authors: Paula S. Hochman, Gustavo Cudkowicz, Jean Dausset
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Decline of Natural Killer Cell Activity in Sublethally Irradiated Mice Get access Paula S. Hochman, Paula S. Hochman 3Departments of Pathology and Microbiology, State University of New York at Buffalo, Buffalo, N.Y. 14214. 4Part of the work reported was undertaken during the tenure of an American Cancer Society-Eleanor Roosevelt International Cancer Travel Fellowship awarded by the International Union Against Cancer to G. C. and a sabbatical fellowship awarded by INSERM. P. S. H. was participating in a predoctoral project abroad. Search for other works by this author on: Oxford Academic PubMed Google Scholar Gustavo Cudkowicz, Gustavo Cudkowicz 3Departments of Pathology and Microbiology, State University of New York at Buffalo, Buffalo, N.Y. 14214. 4Part of the work reported was undertaken during the tenure of an American Cancer Society-Eleanor Roosevelt International Cancer Travel Fellowship awarded by the International Union Against Cancer to G. C. and a sabbatical fellowship awarded by INSERM. P. S. H. was participating in a predoctoral project abroad. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jean Dausset Jean Dausset 5Hôpital Saint Louis, INSERM U93, 2 Place du Docteur Fournier, 75475 Paris, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 61, Issue 1, July 1978, Pages 265–268, https://doi.org/10.1093/jnci/61.1.265 Published: 01 July 1978 Article history Received: 28 December 1977 Accepted: 12 February 1978 Published: 01 July 1978
An outbreak of hepatitis A among south african patients with hemophilia: Evidence implicating contaminated factor VIII concentrate as the source
Authors: Mary-Anne Kedda, Michael C. Kew, Richard J. Cohn, Stephen P. Field, Rosemary Schwyzer, Ernest Song, F. Fernandes-Costa
Journal: Hepatology (1995)

We report an outbreak of hepatitis A in nine South African hemophiliacs treated exclusively with infusions of factor VIII concentrate. The solvent/detergent (S/D) method (which does not inactivate nonenveloped viruses) was used for virus eradication. In three of six patients studied at a molecular level hepatitis A virus (HAV) complementary DNA (cDNA) amplified from serum by reverse transcription-polymerase chain reaction (RT-PCR) was identical to HAV cDNA in 1 of 14 lots (no. 53) of factor VIII tested. The plasma for lot 53 was obtained from donors in the United States: 1 of 12 samples of this source material contained the same HAV cDNA sequences. In another two patients receiving lot 53, the degree of identity between HAV cDNA in serum and that in factor VIII was only 88% and 89%, respectively, and in the sixth patient, who did not receive lot 53, it was 90%. The degree of HAV cDNA homology among five patients in an independent point-source outbreak of hepatitis A was 100%, and that in nine patients who acquired this infection sporadically in Johannesburg, Egypt, or Russia, was 93% to 100%. Whether the three hemophiliacs with low HAV cDNA homology with lot 53 acquired the infection from other unidentified virus strains contaminating factor VIII or from extraneous sources is unknown. This study provides further evidence that factor VIII concentrate prepared by the S/D method may be contaminated by the HAV, in this instance at source, and may cause hepatitis in recipients. Proof of a cause-and-effect relationship will, however, depend on animal inoculation studies.
Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis
Authors: Paul A Monach, Roscoe L Warner, Gunnar Tomasson, Ulrich Specks, John H Stone, Linna Ding, Fernando C Fervenza, Barri J Fessler, Gary S Hoffman, David Iklé, Cees GM Kallenberg, Jeffrey Krischer, Carol A Langford, Mark Mueller, Philip Seo, E William St. Clair, Robert Spiera, Nadia Tchao, Steven R Ytterberg, Kent J Johnson, Peter A Merkel
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objective</h3> To identify circulating proteins that distinguish between active anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and remission in a manner complementary to markers of systemic inflammation. <h3>Methods</h3> Twenty-eight serum proteins representing diverse aspects of the biology of AAV were measured before and 6 months after treatment in a large clinical trial of AAV. Subjects (n=186) enrolled in the Rituximab in ANCA-Associated Vasculitis (RAVE) trial were studied. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were available for comparison. The primary outcome was the ability of markers to distinguish severe AAV (Birmingham Vasculitis Activity Score for Wegener9s granulomatosis (BVAS/WG)≥3 at screening) from remission (BVAS/WG=0 at month 6), using areas under receiver operating characteristic (ROC) curve (AUC). <h3>Results</h3> All subjects had severe active vasculitis (median BVAS/WG=8) at screening. In the 137 subjects in remission at month 6, 24 of the 28 markers showed significant declines. ROC analysis indicated that levels of CXCL13 (BCA-1), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinases-1 (TIMP-1) best discriminated active AAV from remission (AUC&gt;0.8) and from healthy controls (AUC&gt;0.9). Correlations among these markers and with ESR or CRP were low. <h3>Conclusions</h3> Many markers are elevated in severe active AAV and decline with treatment, but CXCL13, MMP-3 and TIMP-1 distinguish active AAV from remission better than the other markers studied, including ESR and CRP. These proteins are particularly promising candidates for future studies to address unmet needs in the assessment of patients with AAV.
STUDIES ON PYROGENIC STEROIDS. I. SEPARATION, IDENTIFICATION, AND MEASUREMENT OF UNCONJUGATED DEHYDROEPIANDROSTERONE, ETIOCHOLANOLONE, AND ANDROSTERONE IN HUMAN PLASMA*
Authors: George L. Cohn, Philip K. Bondy, Carmela Castiglione
Journal: Journal of Clinical Investigation (1961)

Previous studies have shown that endotoxin (1-4), viruses (5-7), and pyrogenic substances from polymorphonuclear leukocytes (8-11) are capable of producing fever.A different group of pyrogenic substances was described by Kappas, Soybel, Fukushima and Gallagher (12), who re- ported that certain C19 and C21 steroids with a 3a-hydroxy, 5/3 configuration produce fever.The prototype compound is etiocholanolone 1 (13-16).Four to 8 hours after intramuscular or intravenous administration of this compound to volun- teers, the temperature began to rise, reached a peak (1030 to 1050 F) at 12 hours, and gener- ally subsided within 24 hours.Chills, anorexia, headache, malaise, myalgia, arthralgia, and leuko- cytosis accompanied the reaction.Recently, Bondy, Cohn, Herrmann and Crispell (16) demonstrated unconjugated 2 etiocholanolone in the plasma of two patients during febrile attacks of etiocholanolone fever.3When the patients were afebrile and asymptomatic, unconju- gated plasma etiocholanolone was not detected.
Neuropilin-1 Upholds Dedifferentiation and Propagation Phenotypes of Renal Cell Carcinoma Cells by Activating Akt and Sonic Hedgehog Axes
Authors: Ying Cao, Ling Wang, Debashis Nandy, Ying Zhang, Ananda Basu, Derek Radisky, Debabrata Mukhopadhyay
Journal: Cancer Research (2008)

Abstract Expression of neuropilin-1 (NRP-1) has been shown in many cancer cells, but its molecular effect on tumorigenesis is largely unknown. In this report, we show that in aggressive types of renal cell carcinoma (RCC), NRP-1 is expressed at a high level. We show that after knockdown of NRP-1 by short hairpin RNA, RCC cells express significantly lower levels of MDM-2 and p63 proteins but higher levels of p53, and exhibit reduced migration and invasion. When implanted in mice, RCC cells with a reduced NRP-1 level have a statistically significant smaller tumor-forming ability than control cells. Also, NRP-1 knockdown RCC cells exhibit a more differentiated phenotype, as evidenced by the expression of epithelial-specific and kidney-specific cadherins, and the inhibition of sonic hedgehog expression participated in this effect. Inhibition of sonic hedgehog expression can be reversed by ΔNp63α overexpression. Our study reveals that NRP-1 helps maintain an undifferentiated phenotype in cancer cells. [Cancer Res 2008;68(21):8667–72]
Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma
Authors: Katelyn T. Byrne, Anik L. Côté, Peisheng Zhang, Shannon M. Steinberg, Yanxia Guo, Rameeza Allie, Weijun Zhang, Marc S. Ernstoff, Edward J. Usherwood, Mary Jo Turk
Journal: Journal of Clinical Investigation (2011)

A link between autoimmunity and improved antitumor immunity has long been recognized, although the exact mechanistic relationship between these two phenomena remains unclear. In the present study we have found that vitiligo, the autoimmune destruction of melanocytes, generates self antigen required for mounting persistent and protective memory CD8+ T cell responses to melanoma. Vitiligo developed in approximately 60% of mice that were depleted of regulatory CD4+ T cells and then subjected to surgical excision of large established B16 melanomas. Mice with vitiligo generated 10-fold larger populations of CD8+ memory T cells specific for shared melanoma/melanocyte antigens. CD8+ T cells in mice with vitiligo acquired phenotypic and functional characteristics of effector memory, suggesting that they were supported by ongoing antigen stimulation. Such responses were not generated in melanocyte-deficient mice, indicating a requirement for melanocyte destruction in maintaining CD8+ T cell immunity to melanoma. Vitiligo-associated memory CD8+ T cells provided durable tumor protection, were capable of mounting a rapid recall response to melanoma, and did not demonstrate phenotypic or functional signs of exhaustion even after many months of exposure to antigen. This work establishes melanocyte destruction as a key determinant of lasting melanoma-reactive immune responses, thus illustrating that immune-mediated destruction of normal tissues can perpetuate adaptive immune responses to cancer.
The Psychiatrist, the Treatment of Chronic Renal Failure, and the Prolongation of Life: III
Authors: HARRY S. ABRAM
Journal: American Journal of Psychiatry (1972)

A study of 30 kidney transplant patients who had received cadaver homografts focused on their overall adaptation, changes in life-style, and the occurrence of the themes of rebirth, ambivalence over accepting a cadaver organ, and death. In general the problems in living with a transplanted kidney did not appear to be overwhelming. Many of the patients expressed relief at their escape from the rigors of dialysis.
Androgen Receptor Signaling in Androgen-Refractory Prostate Cancer
Authors: M. E. Grossmann, H. Huang, D. J. Tindall
Journal: JNCI Journal of the National Cancer Institute (2001)

Prostate cancer is the second most prevalent cancer in males in the United States. Standard therapy relies on removing, or blocking the actions of, androgens. In most cases, this therapy results in a regression of the cancer because the prostate and most primary prostate tumors depend on androgens for growth and the avoidance of apoptosis. However, a portion of the cancers eventually relapse, at which point they are termed "androgen refractory" and can no longer be cured by conventional therapy of any type. The precise molecular events that lead from androgen-sensitive prostate cancer to androgen-refractory prostate cancer are, therefore, of great interest. This review seeks to identify specific molecular events that may be linked directly to the progression to androgen-refractory cancer. Some of the mechanisms appear to involve the androgen receptor (AR) directly and include mutations in, or amplification of, the AR gene in a manner that allows the AR to respond to low doses of androgens, other steroids, or antiandrogens. In a less direct manner, coactivators may increase the sensitivity of the AR to androgens and even other nonandrogenic substances through a number of mechanisms. Additional indirect mechanisms that do not result from mutation of the AR may involve activation of the AR by peptide growth factors or cytokines or may involve bypassing the AR entirely via other cellular pathways. Identification of the role of these mechanisms in the progression to androgen-refractory prostate cancer is critical for developing therapies capable of curing this disease.