tbuckley/cabot-search huggingface dataset:
Reduced α - and β<sub>2</sub>-Adrenergic Vascular Response in Patients with Obstructive Sleep Apnea
Authors: LUDGER GROTE, HOLGER KRAICZI, JAN HEDNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Obstructive sleep apnea (OSA) has been associated with increased sympathetic activity. This study tested the hypothesis that the alpha- and beta(2)-receptor-mediated vascular response is altered in patients with OSA. Forearm vascular resistance was evaluated by venous occlusion plethysmography in 10 normotensive OSA patients and 10 normotensive controls (apnea/hypopnea index [mean +/- SD] 29.4 +/- 2.3 and 1.6 +/- 0.3 per hour, respectively) roughly matched for body mass index (BMI) and age. Forearm vascular resistance was measured after intraarterial infusion of norepinephrine (NE) (7.4, 31, 120, 472 and 1421 pmol/100 ml forearm volume [FAV]/min), before and after phentolamine infusion (2 microgram/100 ml FAV/min), and isoproterenol (ISO) (1, 2, 6, and 15 ng/100 ml FAV/min). NE-induced vasoconstriction was significantly attenuated in OSA patients compared with controls (65.0 +/- 36.6% versus 129.4 +/- 81.8%, p = 0.049). The reduction of vascular resistance after phentolamine was similar in patients and control subjects (-50.8 +/- 16.7% versus -43.4 +/- 20.0%, p = 0.38). During ongoing phentolamine infusion NE increased resistance to a similar extent in both groups (0.5 +/- 4.9% versus -0.9 +/- 10.1%, p = 0.96). Vasodilation following ISO was significantly attenuated in OSA patients compared with control subjects (-53.3 +/- 9.0% versus -64.7 +/- 10.3%, p = 0.049). Moreover, the vascular response to NE in OSA patients was negatively correlated with plasma NE concentration (r = -0.76, p < 0.05). The reduced vascular response to alpha- and beta-receptor stimulation suggests a functional downregulation of vascular sympathoadrenergic receptors in patients with sleep apnea.
THE TREATMENT OF PSORIASIS.
Authors: ARTHUR VAN HARLINGEN
Journal: JAMA (1883)

[Read before the Philadelphia Country Medical Society, October 17, 1883.] Psoriasis is one of the commoner skin diseases met with in this country. The statistics of the American Dermatological Association show that it occurs in the proportion of about 6 per cent, in all diseases of the skin encountered. Daily experience would seem to indicate a still more frequent occurrence, because the affection is a disfiguring and annoying one, and therefore patients are more inclined to seek relief, and also because it is a stubborn disease and greatly prone to relapse. The history of a single case will often extend over many years, and bring it under the observation of a number of different physicians. It is because of the comparative frequency with which psoriasis is met and its stubborness to treatment, that I have selected it as the subject of my remarks this evening. Having had a good deal
Development and Validation of Stroke Risk Equation for Hong Kong Chinese Patients With Type 2 Diabetes
Authors: Xilin Yang, Wing-Yee So, Alice P.S. Kong, Chung-Shun Ho, Christopher W.K. Lam, Richard J. Stevens, Ramon R. Lyu, Donald D. Yin, Clive S. Cockram, Peter C.Y. Tong, Vivian Wong, Juliana C.N. Chan
Journal: Diabetes Care (2006)

We sought to develop stroke risk equations for Chinese patients with type 2 diabetes in Hong Kong.A total of 7,209 Hong Kong Chinese type 2 diabetic patients without a history of stroke at baseline were analyzed. The data were randomly and evenly divided into the training subsample and the test subsample. In the training subsample, stepwise Cox models were used to develop the risk equation. Validation of the U.K. Prospective Diabetes Study (UKPDS) stroke risk engine and the current stroke equation was performed in the test dataset. The life-table method was used to check calibration, and the area under the receiver operating characteristic curve (aROC) was used to check discrimination.A total of 372 patients developed incident stroke during a median of 5.37 years (interquartile range 2.88-7.78) of follow-up. Age, A1C, spot urine albumin-to-creatinine ratio (ACR), and history of coronary heart disease (CHD) were independent predictors. The performance of the UKPDS stroke engine was suboptimal in our cohort. The newly developed risk equation defined by these four predictors had adequate performance in the test subsample. The predicted stroke-free probability by the current equation was within the 95% CI of the observed probability. The aROC was 0.77 for predicting stroke within 5 years. The risk score was computed as follows: 0.0634 x age (years) + 0.0897 x A1C + 0.5314 x log(10) (ACR) (mg/mmol) + 0.5636 x history of CHD (1 if yes). The 5-year stroke probability can be calculated by: 1 - 0.9707(EXP (Risk Score - 4.5674)).Although the risk equation performed reasonably well in Chinese type 2 diabetic patients, external validation is required in other populations.
CONTEMPO 1982: Issues, Frontiers
Authors: Harriet S. Meyer
Journal: JAMA (1982)

Human reproduction is the leitmotiv of CONTEMPO 1982, our fifth annual review issue ofThe Journal. Details of in vitro fertilization from the Jones' laboratory in Norfolk, Va, site of the first in vitro conception resulting in a birth in the United States, are described in our article on Obstetrics and Gynecology. As work proceeds at the frontier of in utero surgery, 1 physicians have already placed catheters and performed ureterostomies for decompression in serious fetal abnormalities, 2-5 and the authors of our articles in Urology and Obstetrics and Gynecology highlight these events. Any assessment of the long-term value of in utero surgical procedures remains preliminary. Such developments also raise ethical questions, whichThe Journalhas tried to address alongside scientific articles. 6,7 The myriad of ethical concerns with the fetus, in special relief this past year, are the subject of the CONTEMPO article on Biomedical Ethics.  To preserve fertility
CORTISONE AND CORTICOTROPIN IN RHEUMATIC FEVER AND JUVENILE RHEUMATOID ARTHRITIS
Authors: Joseph J. Bunim
Journal: JAMA (1952)

To evaluate properly the effects of cortisone on rheumatic fever, it is necessary to divide the many different manifestations of the disease into two categories (table 1). In the first group should be included the systemic or nonspecific clinical and laboratory features of the disease. The second group would comprise manifestations characteristic of rheumatic fever. <h3>NONSPECIFIC CHARACTERISTICS OF RHEUMATIC FEVER</h3> The nonspecific manifestations of rheumatic fever are increased temperature and heart rate, "toxicity," loss of appetite, anemia, elevated erythrocyte sedimentation rate, increased concentration of serum fibrinogen and globulin levels, and the appearance of C-reactive protein (CRP) in the blood. All these nonspecific changes return or tend to return to normal with the administration of cortisone. Most dramatic of these is the prompt subsidence of fever and the toxicity seen in severe cases of rheumatic fever. Another effect is reduction in the sedimentation rate. Of the various constituents of the blood
Pain in Childbirth
Authors: J. Cook
Journal: BMJ (1949)

Synaptic plasticity in the cerebellum is thought to contribute to motor learning. In particular, long-term depression (LTD) at parallel fiber (PF) to Purkinje neuron (PN) excitatory synapses has attracted much attention of neuroscientists as a primary cellular mechanism for motor learning. In contrast, roles of plasticity at cerebellar inhibitory synapses <i>in vivo</i> remain unknown. Here, we have investigated the roles of long-lasting enhancement of transmission at GABAergic synapses on a PN that is known as rebound potentiation (RP). Previous studies demonstrated that binding of GABA<sub>A</sub> receptor with GABA<sub>A</sub> receptor-associated protein (GABARAP) is required for RP, and that a peptide that blocks this binding suppresses RP induction. To address the functional roles of RP, we generated transgenic mice that express this peptide fused to a fluorescent protein selectively in PNs using the PN-specific <i>L7</i> promoter. These mice failed to show RP, although they showed no changes in the basal amplitude or frequency of miniature IPSCs. The transgenic mice also showed no abnormality in gross cerebellar morphology, LTD, or other excitatory synaptic properties, or intrinsic excitability of PNs. Next, we attempted to evaluate their motor control and learning ability by examining reflex eye movements. The basal dynamic properties of the vestibulo-ocular reflex and optokinetic response, and adaptation of the latter, were normal in the transgenic mice. In contrast, the transgenic mice showed defects in the adaptation of vestibulo-ocular reflex, a model paradigm of cerebellum-dependent motor learning. These results together suggest that RP contributes to a certain type of motor learning.
Multiparameter single-cell profiling of human CD4+FOXP3+ regulatory T-cell populations in homeostatic conditions and during graft-versus-host disease
Authors: Shen Dong, Sylvie Maiella, Aliénor Xhaard, Yuanyu Pang, Lynn Wenandy, Jérome Larghero, Christophe Becavin, Arndt Benecke, Elisabetta Bianchi, Gérard Socié, Lars Rogge
Journal: Blood (2013)
Studies on the in vivo and in vitro distribution of apolipoprotein A-IV in human plasma and lymph.
Authors: T Ohta, N H Fidge, P J Nestel
Journal: Journal of Clinical Investigation (1985)

To investigate the unique distribution in plasma of apolipoprotein A-IV (apo A-IV) we have determined, in a series of in vitro and in vivo studies, the redistribution among lipoproteins of 125I-apo A-IV. Free 125I-apo A-IV associated predominantly with high density lipoprotein (HDL) (72 +/- 3.5%) in incubations with plasma, and with triglyceride-rich lipoproteins (TRL) (65 +/- 3.0%) in incubations with lymph, rather than with the lipoprotein-deficient fraction (LDF) where greater than 90% of apo A-IV resides. Incubations with 125I-apo A-IV (incorporated within HDL or TRL) also resulted in similar redistributions of label. Specific radioactivities of apo A-IV in HDL and in TRL were of a similar order and 15-fold higher than those in LDF. However, when 125I-apo A-IV in LDF was incubated with plasma, 57 +/- 2.6% of label remained in the LDF, though the specific radioactivity of apo A-IV in HDL was 15-fold higher than in LDF. Thus, apo A-IV apparently exchanges freely between TRL, HDL, and a part of apo A-IV in LDF, but most of apo A-IV in LDF is refractive to free exchange or transfer. In vivo experiments carried out in five subjects, in which 125I-apo A-IV was injected within TRL, HDL, or LDF, were consistent with the in vitro data in showing rapid exchange of label among plasma apo A-IV containing fractions with much higher specific radioactivities in HDL than in LDF (10-30-fold). However, the small fraction of apo A-IV in LDF that did become labeled was removed from plasma in a biexponential fashion and at the same rate as from HDL. Thus, only a small fraction of the bulk of apo A-IV in plasma LDF exchanges freely with apo A-IV in TRL and HDL, suggesting that apo A-IV in LDF exists in at least two pools. This is consistent with our previous findings that apo A-IV in plasma is present in two distinct complexes with lipids and other peptides.
LONGITUDINAL AND TRANSVERSE LEFT VENTRICULAR MECHANICS IN PATIENTS WITH LOW–EJECTION FRACTION AORTIC STENOSIS: CORRELATION WITH INVASIVE HEMODYNAMICS AND CLINICAL OUTCOMES
Authors: Sheila Sahni, Partho P. Sengupta, Giuseppe Caracciolo, Jagat Narula, Samin Sharma, Annapoorna Kini
Journal: Journal of the American College of Cardiology (2013)
Impaired Bub1 Function <i>In vivo</i> Compromises Tension-Dependent Checkpoint Function Leading to Aneuploidy and Tumorigenesis
Authors: Mark Schliekelman, Dale O. Cowley, Ryan O'Quinn, Trudy G. Oliver, Lucy Lu, E.D. Salmon, Terry Van Dyke
Journal: Cancer Research (2008)

Abstract Bub1 is a serine/threonine kinase originally described as a core component of the spindle assembly checkpoint (SAC) mechanism in yeast. Bub1 binding at kinetochores has been reported to be required for SAC function and localization of other SAC components. A proper SAC is believed to be essential for murine embryonic development, as all previously described null mutations in SAC components in mice cause embryonic lethality. We produced mice harboring a Bub1 mutant allele lacking exons 2 and 3, resulting in a hypomorphic mutant expressed at &amp;lt;5% of wild-type levels. Despite this significant reduction, homozygous mutant animals are viable on a mixed 129P2/B6 or FVB background but display increased tumorigenesis with aging, whereas mice with a C57Bl/6J background die perinatally. Bub1 mutant murine embryonic fibroblasts (MEFs) display defects in chromosome congression to the metaphase plate, severe chromosome missegregation, and aneuploidy accompanied by high levels of premature senescence. Mutant MEFs have a robust SAC in response to nocodazole treatment but an impaired response to Taxol. Mutant MEFs also show reduced kinetochore localization of BubR1, but not of Mad2. The significant reduction in SAC response to Taxol, but not nocodazole, coupled with the reduced binding of BubR1, but not Mad2, indicates that Bub1 is particularly critical for the SAC response to a lack of tension on kinetochores. Thus, Bub1 is essential for proper chromosome segregation, a defect that can lead to severe phenotypes, including perinatal lethality and a predisposition to cancer. [Cancer Res 2009;69(1):45–54]
THE IMMUNOLOGICAL SPECIFICITY OF STAPHYLOCOCCI
Authors: L. A. Julianelle, C. W. Wieghard
Journal: The Journal of Experimental Medicine (1935)

1. Agglutination is not a precise method for the demonstration of serological types among staphylococci. 2. Precipitation of soluble specific substance derived from these organisms demonstrates the existence of at least two immunologically distinct types. 3. The one type, designated A, is composed of apparently virulent strains, while the other, Type B, contains the avirulent strains. 4. Precipitation tests performed with centrifugates of young broth cultures or with acid extracts of sedimented bacteria may also demonstrate type specificity. 5. Lysis by bacteriophage fails to detect the specific types of Staphylococcus. 6. Immunization by intravenous methods stimulates agglutinin formation in all rabbits and precipitin formation in only one of three or four animals. 7. Immunization by repeated intracutaneous injections of dead staphylococci or living organisms in an agar focus also stimulates agglutinin formation but fails to incite the formation of type specific precipitins.
The end of targets?
Authors: D. Spence
Journal: BMJ (2010)

<h3>Abstract</h3> Marine phytoplankton are responsible for about half of the photosynthesis on Earth. Many are mixotrophs, combining photosynthesis with heterotrophic assimilation of organic carbon but the relative contribution of these two carbon sources is not well quantified. Here, single-cell measurements reveal that <i>Prochlorococcus</i> at the base of the photic zone in the Eastern Mediterranean Sea are obtaining only ~20% of carbon required for growth by photosynthesis. Consistently, laboratory-calibrated evaluations of <i>Prochlorococcus</i> photosynthesis indicate that carbon fixation is systematically too low to support published <i>in situ</i> growth rates in the deep photic layer of the Pacific Ocean. Furthermore, agent-based model simulations show that mixotrophic cells maintain realistic growth rates and populations 10s of meters deeper than obligate photo-autotrophs, deepening the nutricline and Deep Chlorophyll Maximum by ~20 m. Time-series of <i>Prochlorococcus</i> ecotype-abundance from the subtropical North Atlantic and North Pacific suggest that up to 30% of the <i>Prochlorococcus</i> cells live where light intensity is not enough to sustain obligate photo-autotrophic populations during warm, stratified periods. Together, these data and models suggest that mixotrophy underpins the ecological success of a large fraction of the global <i>Prochlorococcus</i> population and its collective genetic diversity.
Risk Factors for Physical Impairment after Acute Lung Injury in a National, Multicenter Study
Authors: Dale M. Needham, Amy W. Wozniak, Catherine L. Hough, Peter E. Morris, Victor D. Dinglas, James C. Jackson, Pedro A. Mendez-Tellez, Carl Shanholtz, E. Wesley Ely, Elizabeth Colantuoni, Ramona O. Hopkins
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size.To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization.A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status.At 6 and 12 months, respectively, mean (± SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (± 8%) and 93% (± 9%), 6-minute-walk distance (as percent-predicted) was 64% (± 22%) and 67% (± 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (± 36%) and 67% (± 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes.Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes.
Urinary Excretion of 5-Hydroxyindolacetic Acid in Diarrheal States, with Special Reference to Nontropical Sprue
Authors: O. Dhodanand Kowlessar, Ralph C. Williams, David H. Law, Marvin H. Sleisenger
Journal: New England Journal of Medicine (1958)

URINARY excretion of the serotonin metabolite, 5-hydroxyindolacetic acid, was studied both in normal subjects and in patients with a variety of diarrheal states. Three observations led to this investigation. Circulating 5-hydroxytryptamine (serotonin), which is secreted in large amounts by the tumor, causes the cramping abdominal pain and diarrhea of the malignant carcinoid syndrome.1 , 2 Parenterally administered serotonin has a marked effect upon the gut of man and animals.3 , 4 The precursor of serotonin, 5-hydroxytryptophan, produces nausea, abdominal cramps and borborygmi in human beings.5 Subjects and MethodsTwenty-four-hour specimens of urine were collected from 30 normal adults (house-staff and hospital personnel) and from . . .
Scar collagen deposition in the airways of allografts of lung transplant recipients.
Authors: L Zheng, C Ward, G I Snell, B E Orsida, X Li, J W Wilson, T J Williams, E H Walters
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Collagen subtype deposition has not been studied in the airways of transplanted lungs. As part of rejection, a series of immunologic insults results in a remodeling of the allograft. In chronic rejection, changes in the airway leading to obliterative bronchiolitis syndrome (OBS) are particularly important. To better understand the mechanism of OBS occurring in chronic lung rejection, we investigated deposition of three fibrillar collagens (type I, III, V) in airway biopsies of lung allografts taken from 10 clinically well lung transplant recipients (wLTR) and eight lung transplant recipients (LTR) with OBS (OBLTR) using an immunoperoxidase method. Collagen III deposition and the ratio of collagen type III to type I were found to be significantly increased in OBLTR compared with wLTR (p < 0.05), and the latter correlated inversely with both FEF(25-75) (r = -0.69; p < 0.05) and FEV1 (r = 0.62; p = 0.05) in OBLTR. This suggests that an increased proportion of collagen III in the airway walls of transplanted lungs might be an early signal of the progression to terminal chronic lung allograft dysfunction. The changes in the ratio of type III to type I collagen in the airways of lung allografts may provide important insights into the process of airway remodeling in chronic lung rejection.
How to Evaluate Residents
Authors: Ronald L. Martin
Journal: JAMA (1987)

In 1985, more than 75 000 residents were in more than 4700 accredited graduate medical education programs at 1500 institutions. Are competent physicians being produced? Outside of National Board and FLEX examinations (which may not tap actual clinical performance) and specialty board examinations (which are not obligatory), how do we know? This book may not answer this question explicitly, but it does delineate some options.  The book's first part consists of selections from the proceedings of a conference of the same title held in Chicago in 1986. The second is a selection of previously published articles addressing the problem of resident evaluation in particular specialties. From the outset the editors do not suggest that the book be read from cover to cover. Rather, it is to be sampled selectively according to a reader's particular needs.  It is a book intended for physicians involved in resident education. Thus, it would be
Fibrinogen and Cardiovascular Risk
Authors: Edzard Ernst
Journal: Annals of Internal Medicine (1993)

Letters15 December 1993Fibrinogen and Cardiovascular RiskEdzard Ernst, MD and Karl Ludwig Resch, MDEdzard Ernst, MDSearch for more papers by this author and Karl Ludwig Resch, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-12-199312150-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Several points raised in this letter are relevant. The pharmacologic alteration of fibrinogen seems a grossly under-researched area. Many drugs influence the alteration but often it is difficult to determine if it results from the drug's effect on a given disorder or is a direct effect of the drug itself.That fibrinogen levels increase in intermittent claudication has been observed repeatedly. Recently, Lowe and coworkers [1] reported epidemiologic data showing that the increase is independently associated with peripheral arterial narrowing. Thus, a prognostic relevance of fibrinogen in peripheral arterial occlusive disease comes as little surprise, particularly when considering ...References1. Lowe GD, Fowkes FR, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation. 1993; 87:1915-20. Google Scholar2. Ernst E, Resch KL. Fibrinogen as a cardiovascular risk factor: a meta-analysis and review of the literature. Ann Intern Med. 1993; 118:956-63. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHypofibrinolytic State in HIV-1–Infected Patients Treated With Protease Inhibitor–Containing Highly Active Antiretroviral Therapy 15 December 1993Volume 119, Issue 12Page: 1222-1223KeywordsAtherosclerosisCardiovascular disease riskDrugsEpidemiologyFibrinogenMedical risk factorsPeripheral vascular diseaseResearch designVascular diseases ePublished: 15 August 2000 Issue Published: 15 December 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...