tbuckley/cabot-search huggingface dataset:
Modification of the Relationship of the Apolipoprotein E ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density by Sleep
Authors: Andrew S. P. Lim, Lei Yu, Matthew Kowgier, Julie A. Schneider, Aron S. Buchman, David A. Bennett
Journal: JAMA Neurology (2013)

The apolipoprotein E (APOE [GenBank, 348; OMIM, 107741]) ε4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD). Sleep consolidation is also associated with AD risk, and previous work suggests that APOE genotype and sleep may interact to influence cognitive function.To determine whether better sleep consolidation attenuates the relationship of the APOE genotype to the risk of incident AD and the burden of AD pathology.A prospective longitudinal cohort study with up to 6 years of follow-up was conducted. Participants included 698 community-dwelling older adults without dementia (mean age, 81.7 years; 77% women) in the Rush Memory and Aging Project.We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation and ascertained APOE genotype.Participants underwent annual evaluation for AD during a follow-up period of up to 6 years. Autopsies were performed on 201 participants who died, and β-amyloid (Aβ) and neurofibrillary tangles were identified by immunohistochemistry and quantified.During the follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards regression models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (hazard ratio, 0.67; 95% CI, 0.46-0.97; P = .04 per allele per 1-SD increase in sleep consolidation). In a series of linear mixed-effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline. In individuals who died, better sleep consolidation attenuated the effect of the ε4 allele on neurofibrillary tangle density (interaction estimate, -0.42; SE = 0.17; P = .02), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death.Better sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology. Assessment of sleep consolidation may identify APOE+ individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and development of neurofibrillary tangles in APOE ε4+ individuals.
Noninvasive Diagnosis of Hepatic Fibrosis in Patients With Chronic Hepatitis C by Splenic Doppler Impedance Index
Authors: Chen–Hua Liu, Shih–Jer Hsu, Jou–Wei Lin, Juey–Jen Hwang, Chun–Jen Liu, Pei–Ming Yang, Ming–Yang Lai, Pei–Jer Chen, Jun–Herng Chen, Jia–Horng Kao, Ding–Shinn Chen
Journal: Clinical Gastroenterology and Hepatology (2007)
First trimester fetal growth restriction and cardiovascular risk factors in school age children: population based cohort study
Authors: V. W. V. Jaddoe, L. L. de Jonge, A. Hofman, O. H. Franco, E. A. P. Steegers, R. Gaillard
Journal: BMJ (2014)

<b>Objective</b> To examine whether first trimester fetal growth restriction correlates with cardiovascular outcomes in childhood. <b>Design</b> Population based prospective cohort study. <b>Setting</b> City of Rotterdam, the Netherlands. <b>Participants</b> 1184 children with first trimester fetal crown to rump length measurements, whose mothers had a reliable first day of their last menstrual period and a regular menstrual cycle. <b>Main outcomes measures</b> Body mass index, total and abdominal fat distribution, blood pressure, and blood concentrations of cholesterol, triglycerides, insulin, and C peptide at the median age of 6.0 (90% range 5.7-6.8) years. Clustering of cardiovascular risk factors was defined as having three or more of: high android fat mass; high systolic or diastolic blood pressure; low high density lipoprotein cholesterol or high triglycerides concentrations; and high insulin concentrations. <b>Results</b> One standard deviation score greater first trimester fetal crown to rump length was associated with a lower total fat mass (−0.30%, 95% confidence interval −0.57% to −0.03%), android fat mass (−0.07%, −0.12% to −0.02%), android/gynoid fat mass ratio (−0.53, −0.89 to −0.17), diastolic blood pressure (−0.43, −0.84 to −0.01, mm Hg), total cholesterol (−0.05, −0.10 to 0, mmol/L), low density lipoprotein cholesterol (−0.04, −0.09 to 0, mmol/L), and risk of clustering of cardiovascular risk factors (relative risk 0.81, 0.66 to 1.00) in childhood. Additional adjustment for gestational age and weight at birth changed these effect estimates only slightly. Childhood body mass index fully explained the associations of first trimester fetal crown to rump length with childhood total fat mass. First trimester fetal growth was not associated with other cardiovascular outcomes. Longitudinal growth analyses showed that compared with school age children without clustering of cardiovascular risk factors, those with clustering had a smaller first trimester fetal crown to rump length and lower second and third trimester estimated fetal weight but higher weight growth from the age of 6 months onwards. <b>Conclusions</b> Impaired first trimester fetal growth is associated with an adverse cardiovascular risk profile in school age children. Early fetal life might be a critical period for cardiovascular health in later life.
Astatine-211 conjugated to an anti-CD20 monoclonal antibody eradicates disseminated B-cell lymphoma in a mouse model
Authors: Damian J. Green, Mazyar Shadman, Jon C. Jones, Shani L. Frayo, Aimee L. Kenoyer, Mark D. Hylarides, Donald K. Hamlin, D. Scott Wilbur, Ethan R. Balkan, Yukang Lin, Brian W. Miller, Sofia H. L. Frost, Ajay K. Gopal, Johnnie J. Orozco, Theodore A. Gooley, Kelly L. Laird, Brian G. Till, Tom Bäck, Brenda M. Sandmaier, John M. Pagel, Oliver W. Press
Journal: Blood (2015)
Health Query Language can be used for collecting data from general practices
Authors: K. Allan, P. Murphy
Journal: BMJ (1996)

pc/dos/pgp262i.zip.Use of this software has been advocated by Ross Anderson, who has drawn up for the BMA interim guidelines on maintaining security in computerised information systems.)The Intemnet presents many challenges to the provision of health care,4 but our responses as doctors must be based on critical examination of the facts rather than knee jerk responses to media myths and gross generalisations.
Acute Alcoholic Poisoning
Authors: J. A. Imrie
Journal: BMJ (1955)

Cases -.of mild or medium intoxication are chiefly of medico-legal interest.The more severe states of intoxi- cation are clinical emergencies presenting themselves to the general practitioner, the hospital casualty staff, and the police surgeon.The individuals, concerned are peculiarly liable to a variety of complications, inclu- ding falls, traffic accidents, suffocation by a variety of causes, drowning, exposure, carbon monoxide poison- ing, and electrocution.The subjects of cardiovascular disease may precipitate acute cardiac failure by a debauch, and post-alcoholic debility may be compli- cated by acute pulmonary infections.In the suffocation group, inhalation of vomitus or respiratory obstruction by the tongue or dentures is not infrequent.
Adrenal Cold Abscesses
Authors: J. MARTINEZ L. DE LETONA
Journal: Annals of Internal Medicine (1983)

Letters and Corrections1 September 1983Adrenal Cold AbscessesJ. MARTINEZ L. DE LETONA, M.D., C. MASA VAZQUEZ, M.D., R. PEREZ MAESTU, M.D.J. MARTINEZ L. DE LETONA, M.D.Search for more papers by this author, C. MASA VAZQUEZ, M.D.Search for more papers by this author, R. PEREZ MAESTU, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-3-413_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the recently published update, "The Incidentally Discovered Adrenal Mass," Copeland (1) reviews his experience at the Massachusetts General Hospital, with an extensive search of the literature. We want to add a possibility not included among those described in the paper: a cold adrenal abscess in a patient with Addison's disease of tuberculous origin.A 40-year-old man was referred from another hospital for evaluation of a right adrenal mass detected in a computed-tomographic scan. For the last 10 months he had progressive asthenia and weight loss after an acute episode of vomiting and diarrhea. He did not...Reference1. COPELAND P. The incidentally discovered adrenal mass. Ann Intern Med. 1983;98:940-5. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: J. MARTINEZ L. DE LETONA, M.D.; C. MASA VAZQUEZ, M.D.; R. PEREZ MAESTU, M.D.Affiliations: Clinica Puerto de Hierro Facultad de Medicina Universidad Autónoma de Madrid Madrid, Spain PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTuberculous Addison's disease. Utility of CT in diagnosis and follow-upTuberculose surrénalienne évolutive Intérêt de la tomodensitométrieEscherichia coli Abscess as an Adrenal MassA. ECHANIZ, M.D., JULIO DE MIGUEL PRIETO, M.D., F. ARNAL, M.D., J. D. PEDREIRA, M.D. 1 September 1983Volume 99, Issue 3Page: 413-414KeywordsAbscessesDiarrheaVomitingWeight loss ePublished: 1 December 2008 Issue Published: 1 September 1983 PDF downloadLoading ...
Trends in the Use and Role of Biomarkers in Phase I Oncology Trials
Authors: Bernardo H.L. Goulart, Jeffrey W. Clark, Homer H. Pien, Thomas G. Roberts, Stan N. Finkelstein, Bruce A. Chabner
Journal: Clinical Cancer Research (2007)

Abstract Purpose: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials. Experimental Design: We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts. We analyzed the use of biomarkers and their contribution to published phase I trials. Results: Twenty percent of American Society of Clinical Oncology phase I abstracts (503 of 2458) from 1991 to 2002 included biomarkers. This proportion increased over time (14% in 1991 compared with 26% in 2002; P &amp;lt; 0.02). Independent predictors of the use of biomarkers included National Cancer Institute sponsorship, submission in the time period of 1999 to 2002, adult population, and drug family (biological agents). Biomarkers supported dose selection for phase II studies in 11 of 87 of the trials (13%) emanating from these abstracts. However, the primary determinants of phase II dose and schedule were toxicity and/or efficacy in all but one of these 87 trials (1%). Biomarker studies provided evidence supporting the proposed mechanism of action in 34 of 87 of the published trials (39%). Conclusions: The use of biomarkers in phase I trials has increased over the period from 1991 to 2002. To date, biomarker utilization has made a limited and primarily supportive contribution to dose selection, the primary end point of phase I studies. Additional studies are needed to determine what type of biomarker information is most valuable to evaluate in phase I trials.
A randomised controlled trial of general practitioner safety advice for families with children under 5 years
Authors: M. Clamp, D. Kendrick
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To assess effectiveness of general practitioner advice about child safety, and provision of low cost safety equipment to low income families, on use of safety equipment and safe practices at home. <b>Design:</b> Randomised, unblinded, controlled trial with initial assessment and six week follow up by telephone survey. Twenty families from intervention and control groups were randomly selected for a home visit to assess validity of responses to second survey. <b>Setting:</b> A general practice in Nottingham. <b>Subjects:</b> 98% (165/169) of families with children aged under 5 years registered with the practice. <b>Interventions:</b> General practitioner safety advice plus, for families receiving means tested state benefits, access to safety equipment at low cost. Control families received usual care. <b>Main outcome measures:</b> Possession and use of safety equipment and safe practices at home. <b>Results:</b> Before intervention, the two groups differed only in possession of fireguards. After intervention, significantly more families in intervention group used fireguards (relative risk 1.89, 95% confidence interval 1.18 to 2.94), smoke alarms (1.14, 1.04 to 1.25), socket covers (1.27, 1.10 to 1.48), locks on cupboards for storing cleaning materials (1.38, 1.02 to 1.88), and door slam devices (3.60, 2.17 to 5.97). Also, significantly more families in intervention group showed very safe practice in storage of sharp objects (1.98, 1.38 to 2.83), storage of medicines (1.15, 1.03 to 1.28), window safety (1.30, 1.06 to 1.58), fireplace safety (1.84, 1.34 to 2.54), socket safety (1.77, 1.37 to 2.28), smoke alarm safety (1.11, 1.01 to 1.22), and door slam safety (7.00, 3.15 to 15.6). Stratifying results by receipt of state benefits showed that intervention was at least as effective in families receiving benefits as others. <b>Conclusions:</b> General practitioner advice, coupled with access to low cost equipment for low income families, increased use of safety equipment and other safe practices. These findings are encouraging for provision of injury prevention in primary care. <h3>Key messages</h3> We assessed the effectiveness of general practitioner advice about child safety, and provision of low cost safety equipment to low income families, on safe practices at home The intervention increased safe behaviour and use of safety equipment The intervention was equally effective in families receiving means tested benefits as in those not receiving benefits The effectiveness of this intervention should be evaluated over longer periods, in other practices, and when delivered by other members of the primary healthcare team
The University of Michigan Medical School, 1850-2000
Authors: Howard Markel
Journal: JAMA (2000)

The 150th anniversary of the University of Michigan Medical School affords occasion for both celebration and reflection, not just in Ann Arbor but throughout the world, as we consider its contributions to medical education, research, and health care over the past century and a half. This article explores the medical school's origins as a frontier medical outpost and describes the vital reforms in medical education implemented in Ann Arbor long before the landmark Flexner Report on Medical Education of 1910. It also depicts how and why the medical school developed as it did and what features are distinctive or typical about the school during this period.
Decreased endothelium-dependent hyperpolarization to acetylcholine in smooth muscle of the mesenteric artery of spontaneously hypertensive rats.
Authors: K Fujii, M Tominaga, S Ohmori, K Kobayashi, T Koga, Y Takata, M Fujishima
Journal: Circulation Research (1992)

The endothelium-dependent vascular relaxation to acetylcholine (ACh) in spontaneously hypertensive rats (SHR) may be impaired because of an imbalance of endothelium-derived relaxing factor and contracting factor. However, the role of the endothelium-dependent hyperpolarization remains undetermined. We examined the ACh-induced hyperpolarization and its contribution to relaxation in arteries of SHR. Membrane potentials were recorded from the mesenteric artery trunk of 6-8-month-old male SHR and also Wistar-Kyoto (WKY) rats. Endothelium-dependent hyperpolarization to ACh was unaffected by NG-nitro-L-arginine, indomethacin, or glibenclamide; was reduced by tetraethylammonium or high K+ solution; and was enhanced by low K+ solution or methylene blue, thereby indicating that hyperpolarization is not mediated by nitric oxide (endothelium-derived relaxing factor) but is presumably mediated by a hyperpolarizing factor and is due to an opening of K+ channels that probably differ from the ATP-sensitive ones. Hyperpolarizations to ACh were markedly reduced in SHR compared with findings in WKY rats (maximum, 8 +/- 1 versus 17 +/- 1 mV). In addition, under conditions of depolarization with norepinephrine (10(-5) M), the ACh-induced hyperpolarization was even less and transient in SHR, while it was large and sustained in WKY rats (6 +/- 1 versus 29 +/- 2 mV). Endothelium-dependent relaxations to ACh in arterial rings precontracted with 10(-5) M norepinephrine were far less in SHR than in WKY rats, even in the presence of indomethacin. Furthermore, high K+ solution showed smaller inhibitory effects on the relaxations in SHR than in WKY rats. Endothelium-independent hyperpolarizations and relaxations to cromakalim, a K+ channel opener, were similar between SHR and WKY rats. It would thus appear that the endothelium-dependent hyperpolarization to ACh is reduced in SHR and this would, in part, account for the impaired relaxation to ACh in SHR mesenteric arteries.
Recombinant human soluble thrombomodulin in sepsis-induced disseminated intravascular coagulation: a multicenter propensity score analysis
Authors: Kazuma Yamakawa, Hiroshi Ogura, Satoshi Fujimi, Miki Morikawa, Yoshihito Ogawa, Tomoyoshi Mohri, Yasushi Nakamori, Yoshiaki Inoue, Yasuyuki Kuwagata, Hiroshi Tanaka, Toshimitsu Hamasaki, Takeshi Shimazu
Journal: Intensive Care Medicine (2013)

Evidence of efficacy and safety of, and especially mortality related to, recombinant human thrombomodulin (rhTM) treatment for sepsis-induced disseminated intravascular coagulation (DIC) is limited. We hypothesized that patients with sepsis-induced DIC receiving treatment with rhTM would have improved mortality compared with those with similar acuity who did not.This retrospective cohort study conducted in three tertiary referral hospitals in Japan between January 2006 and June 2011 included all patients with sepsis-induced DIC who required ventilator management. Primary endpoint was in-hospital mortality, with duration of intensive care unit treatment, changes in DIC scores and rate of bleeding complications as secondary endpoints. Regression technique was used to develop a propensity model adjusted for baseline imbalances between groups.Eligible were 162 patients with sepsis-induced DIC; 68 patients received rhTM and 94 did not. Patients receiving rhTM had higher severity of illness according to baseline characteristics. After adjusting for these imbalances by stratified propensity score analysis, treatment with rhTM was significantly associated with reduced in-hospital mortality (adjusted hazard ratio, 0.45; 95 % confidential interval, 0.26-0.77; p = 0.013). An association between rhTM treatment and higher numbers of intensive care unit-free days, ventilator-free days, and vasopressor-free days were observed. DIC scores were significantly decreased in the rhTM group compared with the control group in the early period after rhTM treatment, whereas the incidence of bleeding-related adverse events did not differ between the two groups.Therapy with rhTM may be associated with reduced in-hospital mortality in adult mechanically ventilated patients with sepsis-induced DIC.
The Upper Airway in Pregnancy and Pre-Eclampsia
Authors: Bilgay Izci, Renata L. Riha, Sascha E. Martin, Marjorie Vennelle, Wang A. Liston, Kirsty C. Dundas, Andrew A. Calder, Neil J. Douglas
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Snoring is common in pregnancy, and snoring pregnant women have increased rates of pre-eclampsia. Patients with pre-eclampsia show upper airway narrowing during sleep. The present study aimed to compare upper airway dimensions in pregnant and nonpregnant women and in patients with pre-eclampsia. A total of 50 women in the third trimester of pregnancy and 37 women with pre-eclampsia were recruited consecutively from the antenatal service and matched with 50 nonpregnant women. Upper airway dimensions were measured using acoustic reflection. Comparisons were made by analysis of variance and Student-Newman-Keuls tests. Snoring was reported by 14% of nonpregnant women, 28% of pregnant women, and 75% of pre-eclamptic women (p < 0.001). When seated, pregnant women had wider upper airways than nonpregnant women (p < 0.02), but there was no difference when supine. Oropharyngeal junction area in the seated position was less (p < 0.01) in the women with pre-eclampsia (mean ± SD: 0.9 ± 0.1 cm2) than either nonpregnant (1.1 ± 0.1 cm2) or pregnant women (1.3 ± 0.1 cm2). Supine oropharyngeal junction area was less in the women with pre-eclampsia than in the nonpregnant women (0.8 ± 0.1 versus 1.0 ± 0.1 cm2; p = 0.01) but similar in women with pre-eclampsia and pregnant women (0.9 ± 0.1 cm2; p > 0.3). The study showed that women with pre-eclampsia have upper airway narrowing in both upright and supine postures. These changes could contribute to the upper airway resistance episodes during sleep in patients with pre-eclampsia, which may further increase their blood pressure.
Teleological behaviorism and internal control of behavior
Authors: Albert Silverstein
Journal: Behavioral and Brain Sciences (1995)

Abstract The Aristotelian position on causality advocates explaining biological events by the configuration of outcomes they normally achieve. Rachlin's analysis follows this strategy as an alternative to explanation via hypothetical “inner” events, though he omits considering one definition of “inner” explanation (historical definition) as being complementary to teleological explanation. He also fails to provide a detailed teleological analysis of the role of bridging responses in allowing animals to select larger-outcome alternatives.
<i>Vangl2</i> Acts via RhoA Signaling to Regulate Polarized Cell Movements During Development of the Proximal Outflow Tract
Authors: Helen M. Phillips, Jennifer N. Murdoch, Bill Chaudhry, Andrew J. Copp, Deborah J. Henderson
Journal: Circulation Research (2005)

Loop-tail (Lp) mice develop double outlet right ventricle and aortic arch defects, and the defects are caused by mutations in the Vangl2 gene. Vangl2 mRNA is found in the outflow tract myocardium, including the myocardializing cells that migrate into the outflow tract cushions. Analysis of muscularization of the outflow tract septum showed that this process is compromised in Lp/Lp fetuses. Vangl2 is a component of the noncanonical Wnt, planar cell polarity (PCP) pathway that signals via RhoA. We therefore looked for evidence of polarization in myocardializing cells. In wild-type fetuses, myocardializing cells extend lamellipodia and filopodia into the cushion tissue and reorganize their actin cytoskeleton from a cortical form to stress fibers; behaviors that are characteristic of polarized cells. In contrast, Lp/Lp littermates do not extend lamellipodia or filopodia into the cushion tissue, and their actin remains in a cortical form, suggesting that polarized cell migration of myocardializing cells is inhibited in Lp/Lp. Several other components of the PCP pathway are also localized in the outflow tract myocardium. In wild-type fetuses, the myocardializing cells coexpress RhoA and one of its downstream mediators, ROCK1. RhoA expression is disrupted in Lp/Lp, and is lost from the myocardial-cushion tissue interface, including the presumptive myocardializing cells. These data suggest that Vangl2 is required for the polarization and movement of myocardializing cells into the outflow tract cushions, and that RhoA and ROCK1 are downstream mediators of the PCP signaling pathway in the developing outflow tract.