tbuckley/cabot-search huggingface dataset:
Carotid Artery Dissection
Authors: C. Stapf, M. S. V. Elkind, J. P. Mohr
Journal: Annual Review of Medicine (2000)

Among the large variety of cerebrovascular syndromes, carotid artery dissections remain often under-recognized. Many patients present with minor or transient symptoms, some with local pain only, and some are asymptomatic. A useful rule is that the coincidence of any local pain in neck or face with an ipsilateral Horner’s syndrome preceding transient or persistent retinal or cerebral ischemic symptoms should alert physicians—notably those treating emergencies—to rule out an underlying dissection of the ipsilateral carotid artery. In most cases the extracranial part of the carotid artery is affected; therefore, this review will focus on this main subgroup of patients. We review the pathological anatomy, as well as possible underlying causes, clinical features, diagnostic tools, differential diagnosis, treatment options, and outcome data.
Androgenic and estrogenic activity in water bodies receiving cattle feedlot effluent in Eastern Nebraska, USA.
Authors: Ana M Soto, Janine M Calabro, Nancy V Prechtl, Alice Y Yau, Edward F Orlando, Andreas Daxenberger, Alan S Kolok, Louis J Guillette, Bruno le Bizec, Iris G Lange, Carlos Sonnenschein
Journal: Environmental Health Perspectives (2003)

Studies reveal that surface waters worldwide are contaminated with hormonally active agents, many released from sewage treatment plants. Another potential source of aquatic hormonal contamination is livestock feedlot effluent. In this study, we assessed whether feedlot effluent contaminates watercourses by measuring a) total androgenic [methyltrienolone (R1881) equivalents] and estrogenic (17beta-estradiol equivalents) activity using the A-SCREEN and E-SCREEN bioassays and b) concentrations of anabolic agents via gas chromatography-mass spectroscopy and enzyme-based immunoassays. Water samples were collected over 3 years from up to six sites [all confluent with the Elkhorn River, Nebraska, USA: a feedlot retention pond (site 1), a site downstream from site 1 (site 2), a stream with intermediate livestock impact (site 3), and three sites with no observable livestock impact (sites 4-6)] and two sources of tap water. In 1999, samples from site 1 contained 9.6 pM R1881 equivalents and 1.7 pM 17beta-estradiol equivalents. Site 2 samples had estrogen levels similar to those in site 1 samples but lower androgen levels (3.8 pM R1881 equivalents). Androgen levels in site 3 samples were similar to those in site 2 samples, whereas estrogen levels decreased to 0.7 pM 17beta-estradiol equivalents. At site 6, androgen levels were approximately half those found at site 3, and estrogen levels were comparable with those at site 3. Sampling in later years was limited to fewer sites because of drought and lack of permission to access one site. Instrumental analysis revealed estrone but no significant levels of resorcylic acid lactones or trenbolone metabolites. Tap water was devoid of hormonal activity. We conclude that feedlot effluents contain sufficient levels of hormonally active agents to warrant further investigation of possible effects on aquatic ecosystem health.
Interval between decision and delivery by caesarean section---are current standards achievable? Observational case series
Authors: D. J Tuffnell
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To audit interval from decision to delivery in urgent caesarean section to determine whether the current standard of 30 minutes is achievable routinely; to determine whether delay leads to an excess of admissions to special care. <b>Design:</b> Three audit cycles over four years followed by a continuous audit over 32 months. <b>Setting:</b> Large district general hospital delivering 5500 women each year. <b>Participants:</b> All women delivered by urgent caesarean section for abnormal fetal heart rate patterns, cord prolapse, failed instrumental delivery, or suspected placental abruption. <b>Main outcome measures:</b> Proportion of women delivered within 30 and 40 minutes of decision. Admission rates to special care by length of interval between decision and delivery. <b>Results:</b> In the continuous audit 478 of 721 (66.3%) women were delivered in 30 minutes and 637 (88.3%) within 40 minutes; 29 (4.0%) were undelivered at 50 minutes. If the woman was taken to theatre in 10 minutes, 409 of 500 (81.8%) were delivered in 30 minutes and 495 (97%) in 40 minutes. There was no significant difference in the proportion of babies born at 36 weeks or later who were admitted to special care, when analysed by interval from decision to delivery. 36/449 (8%) babies with an interval from decision to delivery of less than 30 minutes were admitted to special care and 3/23 (13%) with an interval of more than 50 minutes were admitted. <b>Conclusions:</b> The current recommendations for the interval between decision and delivery are not being achieved in routine practice. Failure to meet the recommendations does not seem to increase neonatal morbidity. <h3>What is already known on this topic</h3> Many national bodies recommend that when a decision is made to deliver a baby by caesarean section because of fetal distress, the baby should be delivered within 30 minutes There are no clear classifications of what is urgent nor any evidence that this standard is achievable in routine practice <h3>What this study adds</h3> Delivery within 30 minutes is achievable in only two out of three cases; 88% will be delivered in 40 minutes; up to 4% of women will remain undelivered at 50 minutes Delay in delivery made no difference to the rate of admission to special care for babies over 36 weeks9 gestation
Effects of Atorvastatin on Inflammatory and Fibrinolytic Parameters in Patients with Chronic Kidney Disease
Authors: Marian Goicoechea, Soledad García de Vinuesa, Vicente Lahera, Victoria Cachofeiro, Francisco Gómez-Campderá, Almudena Vega, Soraya Abad, José Luño
Journal: Journal of the American Society of Nephrology (2006)

Although substantial evidence suggests that treatment of dyslipidemia with statins reduces mortality and morbidity that are associated with cardiovascular disease, only a few studies have examined the efficacy of statins on inflammatory and fibrinolytic status in patients with chronic kidney disease (CKD). A 6-mo, prospective, randomized study was designed to assess the efficacy of atorvastatin in reducing circulating inflammatory and fibrinolytic parameters in patients with CKD. Sixty-six patients with CKD (stages 2, 3, and 4) and LDL cholesterol levels > or =100 mg/dl were randomly assigned (2:1) to receive 20 mg/d atorvastatin (n = 44) or nonatorvastatin therapy (n = 22). Lipid profile, renal function, fibrinolytic balance (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1), and inflammatory markers (C-reactive protein [CRP], IL-1 beta, IL-6, and TNF-alpha) were measured before and 6 mo after atorvastatin was added to the treatment. Twenty-five age-matched individuals with normal renal function (estimated GFR >90 ml/min) were used as healthy control subjects. Patients with CKD had higher CRP, IL-1 beta, TNF-alpha, and IL-6 levels than age-matched population with normal renal function. t-PA concentration was higher in patients with CKD (P = 0.000). Plasminogen activator inhibitor-1 values were comparable in all patients. Total cholesterol and LDL cholesterol were significantly reduced only in patients who received atorvastatin. In addition to the hypolipidemic effect, atorvastatin treatment significantly reduced inflammatory parameters: CRP (median 4.1 to 2.9; P = 0.015), TNF-alpha (6.0 +/- 2.7 to 4.7 +/- 2.4; P = 0.046), and IL-1 beta levels (1.9 +/- 0.7 to 1.2 +/- 0.7; P = 0.001). These parameters remained unchanged in patients who were not treated with atorvastatin. Fibrinolytic parameters were not modified by atorvastatin treatment. Patients with CKD showed higher levels of inflammatory parameters and t-PA levels than age-matched healthy control subjects. Atorvastatin treatment, in addition to its beneficial effect on cholesterol levels, improved the inflammatory state of these patients without modifying fibrinolytic balance.
Association of a syndrome resembling Wegener's granulomatosis with low surface expression of HLA class-I molecules
Authors: Hélène T Moins-Teisserenc, Stephan D Gadola, Marina Cella, P Rod Dunbar, Andrew Exley, Neil Blake, Can Baycal, Julien Lambert, Paul Bigliardi, Maria Willemsen, Margaret Jones, Stanislaw Buechner, Marco Colonna, Wolfgang L Gross, Vincenzo Cerundolo
Journal: The Lancet (1999)
Resequencing and Clinical Associations of the 9p21.3 Region
Authors: Andrew D. Johnson, Shih-Jen Hwang, Arend Voorman, Alanna Morrison, Gina M. Peloso, Yi-Hsiang Hsu, George Thanassoulis, Christopher Newton-Cheh, Ian S. Rogers, Udo Hoffmann, Jane E. Freedman, Caroline S. Fox, Bruce M. Psaty, Eric Boerwinkle, L. Adrienne Cupples, Christopher J. O’Donnell
Journal: Circulation (2013)

9p21.3 is among the most strongly replicated regions for cardiovascular disease. There are few reports of sequencing the associated 9p21.3 interval. We set out to sequence the 9p21.3 region followed by a comprehensive study of genetic associations with clinical and subclinical cardiovascular disease and its risk factors, as well as with copy number variation and gene expression, in the Framingham Heart Study (FHS).
Pharmacogenetic Profiling in Patients With Advanced Colorectal Cancer Treated With First-Line FOLFOX-4 Chemotherapy
Authors: Annamaria Ruzzo, Francesco Graziano, Fotios Loupakis, Eliana Rulli, Emanuele Canestrari, Daniele Santini, Vincenzo Catalano, Rita Ficarelli, Paolo Maltese, Renato Bisonni, Gianluca Masi, Gaia Schiavon, Paolo Giordani, Lucio Giustini, Alfredo Falcone, Giuseppe Tonini, Rosarita Silva, Rodolfo Mattioli, Irene Floriani, Mauro Magnani
Journal: Journal of Clinical Oncology (2007)

The objective is to investigate whether polymorphisms with putative influence on fluorouracil/oxaliplatin activity are associated with clinical outcomes of patients with advanced colorectal cancer treated with first-line oxaliplatin, folinic acid, and fluorouracil palliative chemotherapy.Consecutive patients were prospectively enrolled onto medical oncology units in Central Italy. Patients were required to have cytologically/histologically confirmed metastatic disease with at least one measurable lesion. Peripheral blood samples were used for genotyping 12 polymorphisms in thymidylate synthase, methylenetetrahydrofolate reductase, xeroderma pigmentosum group D (XPD), excision repair cross complementing group 1 (ERCC1), x-ray cross complementing group 1, x-ray cross complementing protein 3, glutathione S-transferases (GSTs) genes. The primary end point of the study was to investigate the association between genotypes and progression-free survival (PFS).In 166 patients, ERCC1-118 T/T, XPD-751 A/C, and XPD-751 C/C genotypes were independently associated with adverse PFS. The presence of two risk genotypes (ERCC1-118 T/T combined with either XPD-751 A/C or XPD-751 C/C) occurred in 50 patients (31%). This profiling showed an independent role for unfavorable PFS with a hazard ratio of 2.84% and 95% CI of 1.47 to 5.45 (P = .002). Neurotoxicity was significantly associated with GSTP1-105 A/G. Carriers of the GSTP1-105 G/G genotype were more prone to suffer from grade 3 neurotoxicity than carriers of GSTP1-105 A/G and GSTP1-105 A/A genotypes.A pharmacogenetic approach may be an innovative strategy for optimizing palliative chemotherapy in patients with advanced colorectal cancer. These findings deserve confirmation in additional prospective studies.
Dual mechanisms of regulation of type I iodothyronine 5'-deiodinase in the rat kidney, liver, and thyroid gland. Implications for the treatment of hyperthyroidism with radiographic contrast agents.
Authors: D L St Germain
Journal: Journal of Clinical Investigation (1988)

Alterations in thyroid hormone status and the administration of radiographic contrast agents can markedly influence iodothyronine metabolism and, in particular, the activity of type I 5'-deiodinase (5'DI). In the present studies, the mechanisms responsible for these effects have been reassessed. As previously reported, the addition of iopanoic acid (IOP) to broken cell preparations resulted in a competitive pattern of 5'DI inhibition. However, the in vivo administration to rats of IOP or 3,3',5'-triiodothyronine (rT3) resulted in a noncompetitive pattern of inhibition of 5'DI in the liver, kidney, and thyroid gland, whereby marked decreases in maximal enzyme velocity (V max) were noted, with no change in the value of the Michaelis-Menten constant. In rats rendered hyperthyroid by the injection of 3,5,3'-triiodothyronine (T3), 5'DI activity was significantly increased in the liver and the kidney. The administration of IOP to these thyrotoxic animals resulted in a rapid loss of enzyme activity characterized by an approximate 80% decrease in 5'DI V max values in both tissues. Furthermore, this inhibitory effect persisted for longer than 60 h after a single IOP injection. IOP administration also decreased 5'DI V max levels in the thyroid gland by 52%. In other experiments, treatment of intact Reuber FAO hepatoma cells with IOP or rT3 induced a rapid decrease in 5'DI V max levels. In cells treated with cycloheximide, these agents enhanced the rate of disappearance of enzyme activity by greater than 12-fold, indicating a predominant effect on accelerating the rate of enzyme inactivation and/or degradation. These studies demonstrate that iodothyronines and other iodinated compounds have complex regulatory effects on 5'DI that entail alterations in the rates of both enzyme activation and inactivation. The previously accepted concept that rT3 and IOP impair thyroxine (T4) to T3 conversion in vivo by acting as competitive inhibitors is an oversimplification. Rather, the clinically beneficial effects of administering these agents to patients with hyperthyroidism may result primarily from the rapid and prolonged inactivation of 5'DI which occurs in the thyroid gland and peripheral tissues.
The Apolipoprotein E Knockout Mouse
Authors: Moriz Buzello, Johannes Törnig, Jörg Faulhaber, Heimo Ehmke, Eberhard Ritz, Kerstin Amann
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. Rodents do not develop spontaneous atherosclerosis. Currently, there is no good animal model to study the effect of uremia on atherosclerosis. This study evaluated whether apolipoprotein E knockout (Apoe−/−) mice are useful to study the effect of renal dysfunction on cardiovascular risk. Apoe−/− mice have decreased serum apolipoprotein E and exhibit lipid abnormalities and atherosclerosis even on a low-cholesterol diet. Ten-wk-old Apoe−/− mice were subtotally nephrectomised (SNX Apoe−/−; n = 8), uninephrectomised (UNX Apoe−/−; n = 5), or sham-operated (sham Apoe−/−; n = 5) and compared with their genetic controls (SNX C57/BL6; UNX C57/BL6; sham C57/BL6). After 12 wk, BP was measured intraarterially, blood samples were taken, and the experiment was terminated by perfusion fixation. The heart weight was determined, and quantitative morphologic analysis of intramyocardial arteries and aortic changes was performed. At the end of the experiment, heart weight and relative left ventricular weight were comparable in all groups. Intraarterial BP was somewhat higher in Apoe−/− mice compared with controls. Baseline serum cholesterol and triglyceride levels were higher in Apoe−/− mice than in C57/BL6. Atherosclerotic plaques were not present in sham or UNX C57/BL6, but minor plaque formation was noted in some SNX control animals. In contrast, beginning plaques were seen even in untouched Apoe−/− mice, and strikingly increased plaque formation was noted in UNX and SNX Apoe−/− mice. Maximal plaque diameter (cross-section) was 37 ± 74 μm in SNX C57/BL6, 191 ± 90 μm in sham Apoe−/−, 323 ± 66 μm in UNX Apoe−/−, and 457 ± 17 μm in SNX Apoe−/−. The plaque morphology corresponded with that of early plaques characterized by foam cells and virtual absence of lymphocytes or smooth muscle cell infiltration. In conclusion, even mild renal dysfunction, i.e., after uninephrectomy, causes a dramatic increase in plaque size and aggressive morphology (foam cell rich soft plaques) in the animal model of the Apoe−/− mouse. E-mail: [email protected]
Multiple T Cell Subsets Control <i>Francisella tularensis</i> LVS Intracellular Growth Without Stimulation Through Macrophage Interferon γ Receptors
Authors: Siobhán C. Cowley, Karen L. Elkins
Journal: The Journal of Experimental Medicine (2003)

A variety of data suggest that in vivo production of interferon (IFN)-γ is necessary, but not sufficient, for expression of secondary protective immunity against intracellular pathogens. To discover specific IFN-γ–independent T cell mediated mechanisms, we took advantage of an in vitro culture system that models in vivo immune responses to the intracellular bacterium Francisella tularensis live vaccine strain (LVS). LVS-immune lymphocytes specifically controlled 99% of the growth of LVS in wild-type murine bone marrow–derived macrophages. Surprisingly, LVS-immune lymphocytes also inhibited LVS intracellular growth by as much as 95% in macrophages derived from IFN-γ receptor knockout (IFNγR KO) mice. CD8+ T cells, and to a lesser degree CD4+ T cells, controlled LVS intracellular growth in both wild-type and IFNγR KO macrophages. Further, a unique population of Thy1+αβ+CD4−CD8− cells that was previously suggested to operate during secondary immunity to LVS in vivo strongly controlled LVS intracellular growth in vitro. A large proportion of the inhibition of LVS intracellular growth in IFNγR KO macrophages by all three T cell subsets could be attributed to tumor necrosis factor (TNF) α. Thus, T cell mechanisms exist that control LVS intracellular growth without acting through the IFN-γ receptor; such control is due in large part to TNF-α, and is partially mediated by a unique double negative T cell subpopulation.
A comparison of the physiological profiles of elite Gaelic footballers, hurlers, and soccer players: Table 1
Authors: M C McIntyre
Journal: British Journal of Sports Medicine (2005)

Background: Gaelic football, soccer, and hurling are prominent field games in Ireland and involve participants undertaking a variety of playing tasks and skills which place various physiological demands on the participants. The aim of this study was to evaluate and compare the mid-season physiological profiles of elite players. Methods: Physiological assessment was carried out on 29 inter-county Gaelic footballers, 30 inter-county hurlers, and 21 League of Ireland soccer players. Results: Significant differences were reported for % body fat (p&lt;0.05), aerobic capacity (p&lt;0.05), flexibility (p&lt;0.05), upper body strength (p&lt;0.05), upper body strength endurance (p&lt;0.05), abdominal endurance (p&lt;0.05), and speed endurance (p&lt;0.05), while there were no differences recorded for height, weight, or speed levels. A relatively heterogeneous body size is evident for all three sports. Soccer players had lower body fat levels, greater aerobic capacity, greater strength endurance, and greater flexibility compared to both Gaelic footballers and hurlers, possibly due to specific training and conditioning programmes or physical adaptation to match play The greater strength of both Gaelic footballers and hurlers and the superior speed endurance levels of Gaelic footballers also reflect the physical nature of the sports. Similar speed levels amongst all three sports reflect the importance of speed for performance. Conclusions: The various physiological attributes for Gaelic football, soccer, and hurling reflect the physical requirements for success and participation in each of these field games.
Intrajejunal volatile fatty acids in the stagnant loop syndrome
Authors: A. J. Chernov, W. F. Doe, D. Gompertz
Journal: Gut (1972)

In the stagnant loop syndrome an abnormal anaerobic flora colonizes the small bowel. Anaerobic organisms are characterized by fermentation reactions leading to the production of volatile fatty acids. This paper describes the measurement of intrajejunal volatile fatty acid concentrations in 11 patients with the stagnant loop syndrome. Nine normal persons and 18 patients with gastrointestinal disease without intestinal stasis acted as controls. Acetate and propionate concentrations were greatly increased in the patients with the stagnant loop syndrome and returned to normal in those patients treated with antibiotics. The measurement of intrajejunal volatile fatty acid concentrations as an index of overgrowth of anaerobic organisms is discussed.
Neurological and Behavioral Consequences of Childhood Lead Exposure
Authors: David C Bellinger
Journal: PLoS Medicine (2008)

Among environmental chemicals, lead's reputation as a “bad actor” is confirmed in study after study. Over the past 30 years, we have learned that its toxicities are expressed in many forms, and, unfortunately, at levels of exposure that are still prevalent in the general population. The United States Centers for Disease Control and Prevention's current screening guidelines for preventing lead poisoning in young children suggest that screening should be targeted at identifying those with a blood lead level of 10 μg/dl or more [1]. However, this level has no special biological significance and certainly should not be interpreted as “safe.” Indeed, a “safe” level has yet to be found. Two new studies published in this issue of PLoS Medicine, both from the long-running Cincinnati Lead Study (CLS), extend our knowledge of lead's effects and their societal implications [2,3].
Selective Permeabilization of the Blood–Brain Barrier at Sites of Metastasis
Authors: John J. Connell, Grégoire Chatain, Bart Cornelissen, Katherine A. Vallis, Alastair Hamilton, Len Seymour, Daniel C. Anthony, Nicola R. Sibson
Journal: JNCI Journal of the National Cancer Institute (2013)

Effective chemotherapeutics for primary systemic tumors have limited access to brain metastases because of the blood–brain barrier (BBB). The aim of this study was to develop a strategy for specifically permeabilizing the BBB at sites of cerebral metastases. BALB/c mice were injected intracardially to induce brain metastases. After metastasis induction, either tumor necrosis factor (TNF) or lymphotoxin (LT) was administered intravenously, and 2 to 24 hours later gadolinium- diethylenetriaminepentaacetic acid, horseradish peroxidase, or radiolabeled trastuzumab (111In-BnDTPA-Tz) was injected intravenously. BBB permeability was assessed in vivo using gadolinium-enhanced T1-weighted magnetic resonance imaging and confirmed histochemically. Brain uptake of 111In-BnDTPA-Tz was determined using in vivo single photon emission computed tomography/computed tomography. Endothelial expression of TNF receptors was determined immunohistochemically in both mouse and human brain tissue containing metastases. Group differences were analyzed with one-way analysis of variance followed by post hoc tests, Wilcoxon signed rank test, and Kruskal–Wallis with Dunn's multiple comparison test. All statistical tests were two-sided. Localized expression of TNF receptor 1 (TNFR1) was evident on the vascular endothelium associated with brain metastases. Administration of TNF or LT permeabilized the BBB to exogenous tracers selectively at sites of brain metastasis, with peak effect at 6 hours. Metastasis-specific uptake ratio of 111In-BnDTPA-Tz was also demonstrated after systemic TNF administration vs control (0.147±0.066 vs 0.001±0.001). Human brain metastases displayed a similar TNF receptor profile compared with the mouse model, with predominantly vascular TNFR1 expression. These findings describe a new approach to selectively permeabilize the BBB at sites of brain metastases to aid in detection of micrometastases and facilitate tumor-specific access of chemotherapeutic agents. We hypothesize that this permeabilization works primarily though TNFR1 activation and has the potential for clinical translation.