tbuckley/cabot-search huggingface dataset:
Refugees pose little health risk, says WHO
Authors: Anne Gulland
Journal: BMJ (2015)

The World Health Organization has sought to dispel any fears that refugees arriving in Europe may bring infectious diseases with them.

In the wake of growing concern over the refugee crisis and scenes of chaos and despair in Hungary and Turkey last week, Zsuzsanna Jakab, WHO regional director for Europe, has issued a statement saying that no “systematic association” exists between migration and the importation of infectious diseases. She said that communicable diseases were primarily associated with poverty.

“The risk that exotic infectious agents, such as Ebola virus or Middle East respiratory coronavirus (MERS-CoV), will be imported into Europe is extremely low, and experience has shown that, when it occurs, it affects regular travellers, tourists, or healthcare workers rather than refugees or migrants,” …
Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation.
Authors: D E Wilson, M Emi, P H Iverius, A Hata, L L Wu, E Hillas, R R Williams, J M Lalouel
Journal: Journal of Clinical Investigation (1990)

Familial lipoprotein lipase (LPL) deficiency is a rare genetic disorder accompanied by well-characterized manifestations. The phenotypic expression of heterozygous LPL deficiency has not been so clearly defined. We studied the pedigree of a proband known to be homozygous for a mutation resulting in nonfunctional LPL. Hybridization of DNA from 126 members with allele-specific probes detected 29 carriers of the mutant allele. Adipose tissue LPL activity, measured previously, was reduced by 50% in carriers, but did not reliably distinguish them from noncarriers. Carriers were prone to the expression of a form of familial hypertriglyceridemia characterized by increased plasma triglyceride, VLDL cholesterol and apolipoprotein B, and decreased LDL and HDL cholesterol concentrations. These manifestations were age modulated, with conspicuous differences between carriers and noncarriers observed only after age 40. Several noncarriers exhibited similar lipid abnormalities, but without the inverse relationship between VLDL cholesterol and LDL cholesterol noted among carriers. In addition to age and carrier status, the potentially reversible conditions, obesity, hyperinsulinemia and lipid-raising drug use were contributory. Thus heterozygous lipoprotein lipase deficiency, together with age-related influences, may account for a form of familial hypertriglyceridemia.
Histopathologic Classification of ANCA-Associated Glomerulonephritis
Authors: Annelies E. Berden, Franco Ferrario, E. Christiaan Hagen, David R. Jayne, J. Charles Jennette, Kensuke Joh, Irmgard Neumann, Laure-Hélène Noël, Charles D. Pusey, Rüdiger Waldherr, Jan A. Bruijn, Ingeborg M. Bajema
Journal: Journal of the American Society of Nephrology (2010)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis worldwide, and the renal biopsy is the gold standard for establishing the diagnosis. Although the prognostic value of the renal biopsy in ANCA-associated glomerulonephritis is widely recognized, there is no consensus regarding its pathologic classification. We present here such a pathologic classification developed by an international working group of renal pathologists. Our classification proposes four general categories of lesions: Focal, crescentic, mixed, and sclerotic. To determine whether these lesions have predictive value for renal outcome, we performed a validation study on 100 biopsies from patients with clinically and histologically confirmed ANCA-associated glomerulonephritis. Two independent pathologists, blinded to patient data, scored all biopsies according to a standardized protocol. Results show that the proposed classification system is of prognostic value for 1- and 5-year renal outcomes. We believe this pathologic classification will aid in the prognostication of patients at the time of diagnosis and facilitate uniform reporting between centers. This classification at some point might also provide means to guide therapy.
Shifting gears: liver SR-BI drives reverse cholesterol transport in macrophages
Authors: A. E. van der Velde
Journal: Journal of Clinical Investigation (2005)

Cholesterol efflux from macrophages, the first step in reverse cholesterol transport (RCT), is assumed to play a critical role in the pathogenesis of atherosclerosis. However, in vivo proof supporting this hypothesis is lacking, due to difficulties in determining the activity of this first step in RCT. In this issue of the JCI, Zhang et al. apply their recently developed method for measuring RCT in vivo to estimate RCT in mouse models with varying levels of HDL turnover. A surprisingly efficient clearance of cholesterol to feces is observed in mice overexpressing hepatic scavenger receptor class B type I (SR-BI), whereas in SR-BI–knockout mice, cholesterol clearance is diminished. The study demonstrates that hepatic SR-BI is a positive regulator of macrophage RCT in vivo.
Combination of the mTOR Inhibitor Ridaforolimus and the Anti-IGF1R Monoclonal Antibody Dalotuzumab: Preclinical Characterization and Phase I Clinical Trial
Authors: Serena Di Cosimo, Sriram Sathyanarayanan, Johanna C. Bendell, Andrés Cervantes, Mark N. Stein, Irene Braña, Desamparados Roda, Brian B. Haines, Theresa Zhang, Christopher G. Winter, Sharda Jha, Youyuan Xu, Jason Frazier, Richard A. Klinghoffer, Ann Leighton-Swayze, Yang Song, Scot Ebbinghaus, José Baselga
Journal: Clinical Cancer Research (2014)

Mammalian target of rapamycin (mTOR) inhibition activates compensatory insulin-like growth factor receptor (IGFR) signaling. We evaluated the ridaforolimus (mTOR inhibitor) and dalotuzumab (anti-IGF1R antibody) combination.In vitro and in vivo models, and a phase I study in which patients with advanced cancer received ridaforolimus (10-40 mg/day every day × 5/week) and dalotuzumab (10 mg/kg/week or 7.5 mg/kg/every other week) were explored.Preclinical studies demonstrated enhanced pathway inhibition with ridaforolimus and dalotuzumab. With 87 patients treated in the phase I study, main dose-limiting toxicities (DLT) of the combination were primarily mTOR-related stomatitis and asthenia at doses of ridaforolimus lower than expected, suggesting blockade of compensatory pathways in normal tissues. Six confirmed partial responses were reported (3 patients with breast cancer); 10 of 23 patients with breast cancer and 6 of 11 patients with ER(+)/high-proliferative breast cancer showed antitumor activity.Our study provides proof-of-concept that inhibiting the IGF1R compensatory response to mTOR inhibition is feasible with promising clinical activity in heavily pretreated advanced cancer, particularly in ER(+)/high-proliferative breast cancer (ClinicalTrials.gov identifier: NCT00730379).
Relation between JAK2 (V617F) mutation status, granulocyte activation, and constitutive mobilization of CD34+ cells into peripheral blood in myeloproliferative disorders
Authors: Francesco Passamonti, Elisa Rumi, Daniela Pietra, Matteo G. Della Porta, Emanuela Boveri, Cristiana Pascutto, Laura Vanelli, Luca Arcaini, Sara Burcheri, Luca Malcovati, Mario Lazzarino, Mario Cazzola
Journal: Blood (2005)
Circulatory Changes Following Birth of the Calf and the Effect of Hypoxia
Authors: JOHN T. REEVES, JAMES E. LEATHERS
Journal: Circulation Research (1964)

Circulatory and ventilatory measurements were made during the course of 66 cardiac catheterizations in 20 unanesthetized Jersey calves, age two hours to eight weeks. The salient findings were: 1. The pulmonary arterial pressure was high during the first two to three hours of extra-uterine life (up to 80 mm Hg) and it decreased rapidly (30 to 40 mm Hg) during the next nine to ten hours. 2. The pulmonary ventilation appeared good, judging by the active appearance of the calves, the volumes of respired air, the arterial blood gases, and the ventilatory response to hypoxia. 3. The pulmonary blood flows in these calves were not higher in the first hours of life than on subsequent days, and there was little contribution to the pulmonary blood flow by a left to right shunt through the ductus arteriosus. 4. Hypoxia, if severe, could increase the pulmonary arterial pressure to systemic levels on the day of birth, but not in older calves. 5. Pulmonary vasoconstriction sometimes followed puncture of the aorta or other procedures in calves less than twelve hours old. The lability of the pulmonary blood vessels during the first hours of extra-uterine life suggested that large changes in pulmonary vascular tone also occur in utero.
Effectiveness of switching from adjuvant tamoxifen to anastrozole in postmenopausal women with hormone-sensitive early-stage breast cancer: a meta-analysis
Authors: Walter Jonat, Michael Gnant, Francesco Boccardo, Manfred Kaufmann, Alessandra Rubagotti, Ivan Zuna, Mike Greenwood, Raimund Jakesz
Journal: The Lancet Oncology (2006)
Associations of the IL12B promoter polymorphism in longitudinal data from asthmatic patients 7 to 42 years of age
Authors: Siew-Kim Khoo, Catherine M. Hayden, Mary Roberts, Elisabeth Horak, Nick de Klerk, Guicheng Zhang, Colin F. Robertson, Jack Goldblatt, Peter Le Souëf
Journal: Journal of Allergy and Clinical Immunology (2004)
Contrasting Actions of Endothelin ET<sub>A</sub>and ET<sub>B</sub>Receptors in Cardiovascular Disease
Authors: Markus P. Schneider, Erika I. Boesen, David M. Pollock
Journal: The Annual Review of Pharmacology and Toxicology (2006)

First identified as a powerful vasoconstrictor, endothelin has an extremely diverse set of actions that influence homeostatic mechanisms throughout the body. Two receptor subtypes, ET(A) and ET(B), which usually have opposing actions, mediate the actions of endothelin. ET(A) receptors function to promote vasoconstriction, growth, and inflammation, whereas ET(B) receptors produce vasodilation, increases in sodium excretion, and inhibit growth and inflammation. Potent and selective receptor antagonists have been developed and have shown promising results in the treatment of cardiovascular diseases such as pulmonary arterial hypertension, acute and chronic heart failure, hypertension, renal failure, and atherosclerosis. However, results are often contradictory and complicated because of the tissue-specific vasoconstrictor actions of ET(B) receptors and the fact that endothelin is an autocrine and paracrine factor whose activity is difficult to measure in vivo. Considerable questions remain regarding whether ET(A)-selective or nonselective ET(A)/ET(B) receptor antagonists would be useful in a range of clinical settings.
Among diffuse large B-cell lymphomas, T-cell-rich/histiocyte-rich BCL and CD30 + anaplastic B-cell subtypes exhibit distinct clinical features
Authors: B. Maes, A. Anastasopoulou, J.C. Kluin-Nelemans, I. Teodorovic, R. Achten, A. Carbone, C. De Wolf-Peeters
Journal: Annals of Oncology (2001)
Rituximab in Children with Resistant Idiopathic Nephrotic Syndrome
Authors: Alberto Magnasco, Pietro Ravani, Alberto Edefonti, Luisa Murer, Luciana Ghio, Mirco Belingheri, Elisa Benetti, Corrado Murtas, Giovanni Messina, Laura Massella, Maria Gabriella Porcellini, Michela Montagna, Mario Regazzi, Francesco Scolari, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2012)

Idiopathic nephrotic syndrome resistant to standard treatments remains a therapeutic dilemma in pediatric nephrology. To test whether the anti-CD20 monoclonal antibody rituximab may benefit these patients, we conducted an open-label, randomized, controlled trial in 31 children with idiopathic nephrotic syndrome unresponsive to the combination of calcineurin inhibitors and prednisone. All children continued prednisone and calcineurin inhibitors at the doses prescribed before enrollment, and one treatment group received two doses of rituximab (375 mg/m(2) intravenously) as add-on therapy. The mean age was 8 years (range, 2-16 years). Rituximab did not reduce proteinuria at 3 months (change, -12% [95% confidence interval, -73% to 110%]; P=0.77 in analysis of covariance model adjusted for baseline proteinuria). Additional adjustment for previous remission and interaction terms (treatment by baseline proteinuria and treatment by previous remission) did not change the results. In conclusion, these data do not support the addition of rituximab to prednisone and calcineurin inhibitors in children with resistant idiopathic nephrotic syndrome.
Novel Approaches Are Needed to Develop Tomorrow’s Antibacterial Therapies
Authors: Brad Spellberg, John Bartlett, Rich Wunderink, David N. Gilbert
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<Why Has New Antibiotic De...What Can Be Done to Stimu...What Are the Implications...ConclusionsReferencesCITING ARTICLES
Gallbladder sludge: Spontaneous course and incidence of complications in patients without stones
Authors: Paul Janowitz, Wolfgang Kratzer, Thomas Zemmler, Jürgen Tudyka, Johannes G. Wechsler
Journal: Hepatology (1994)

Although the ultrasonic detection of gallbladder sludge is relatively frequent, its clinical importance remains unclear, partly because of the paucity of reliable investigations regarding its natural course in patients without stones. In a retrospective study we investigated the course and clinical significance of gallbladder sludge in patients without stones or other identified gallbladder abnormalities. The diagnosis of gallbladder sludge was made by ultrasound scan in 286 (1.7%) of 17,021 patients. The mean follow-up period for these patients was 20.3 ± 11.5 mo. Of this group 56 patients were without both stones and sludge at the initial examination, and gallbladder sludge developed after a mean observation period of 11.2 ± 10.6 mo. Within 2.0 ± 3.5 mo after sludge detection, 40 (71.4%) patients were free of sludge and showed normal gallbladder findings. Gallbladder stones without sludge persistence developed in five patients (8.9%) within 2.5 ± 0.6 mo after diagnosis of sludge, and gallstones with persistence of sludge developed in two other patients (3.6%) after 6.1 and 30.7 mo, respectively. In no cases did the stones become clinically symptomatic in the course of the follow-up period. Acute acalculous cholecystitis developed in four patients (7.1%) from 6.5 to 37.5 mo after the first examination. In five patients, sludge persisted after a mean 22.3 ± 13.5 mo of follow-up. Although our data show that gallbladder sludge disappeared spontaneously within a relatively short time in 71.4% of patients, gallbladder sludge must be considered an important pathologic entity because gallbladder stones or complications such as acute cholecystitis occurred in 19.6% of patients. It remains for prospective studies to investigate whether therapy of gallbladder sludge may reduce the incidence of complications, particularly the development of gallstones and acute cholecystitis. We were not able to observe acute pancreatitis at least for the first year after sludge development. (Hepatology 1994;20:291–294.)
MicroRNAs As Onco-miRs, Drivers of Cancer
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2010)

Evidence has been mounting for a decade that small regulatory RNAs called microRNAs (miRNAs) are linked to cancer formation and progression. But miRNAs ’ role as a driver of cancer has been less certain. Now animal studies are offering the fi rst tantalizing hints that some miRNAs, known as onco-miRs, can actually set tumor formation in motion and that restoring the function of tumor-suppressing miRNA can eliminate tumors. Many studies have reported that specifi c miRNAs, which bind to complementary sites on mRNAs and prevent their translation into proteins, are associated with more invasive cancers. But these fi ndings all
Association between age and knee structural change: a cross sectional MRI based study
Authors: C Ding
Journal: Annals of the Rheumatic Diseases (2005)

To describe the associations between age, knee cartilage morphology, and bone size in adults.A cross sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee measures included a cartilage defect five site score (0-4 respectively) and prevalence (defect score of > or =2 at any site), cartilage volume and thickness, and bone surface area and/or volume. These were determined at the patellar, medial, and lateral tibial and femoral sites using T(1)weighted fat saturation MRI. Height, weight, and radiographic osteoarthritis (ROA) were measured by standard protocols.In multivariate analysis, age was significantly associated with knee cartilage defect scores (beta = +0.016 to +0.073/year, all p<0.01) and prevalence (OR = 1.05-1.10/year, all p<0.05) in all compartments. Additionally, age was negatively associated with knee cartilage thickness at all sites (beta = -0.013 to -0.035 mm/year, all p<0.05), and with patellar (beta = -11.5 microl/year, p<0.01) but not tibial cartilage volume. Lastly, age was significantly positively associated with medial and lateral tibial surface bone area (beta = +3.0 to +4.7 mm(2)/year, all p<0.05) and patellar bone volume (beta = +34.4 microl/year, p<0.05). Associations between age and tibiofemoral cartilage defect score, cartilage thickness, and bone size decreased in magnitude after adjustment for ROA, suggesting these changes are directly relevant to OA.The most consistent knee structural changes with increasing age are increase in cartilage defect severity and prevalence, cartilage thinning, and increase in bone size with inconsistent change in cartilage volume. Longitudinal studies are needed to determine which of these changes are primary and confirm their relevance to knee OA.
An epidemiological study of the influence of season (cold and dry air) on the occurrence of irritant skin changes of the hands
Authors: None Uter, None Gefeller, None Schwanitz
Journal: British Journal of Dermatology (1998)

In the course of an ongoing cohort study on constitutional and occupational risk factors for the development of irritant hand dermatitis in hairdressing apprentices, an increased prevalence of irritant skin changes was noted in a subgroup examined during particularly cold winter months. Prompted by this observation, the importance of several meteorological factors (day means of temperature, relative and absolute humidity) was assessed in extensive statistical analyses based on data of 742 participants, supplemented by meteorological information obtained from the German Meteorological Service (DWD). There were significant associations of existing hand dermatitis with low temperature and low absolute humidity (Mann-Whitney U-test, P < 0.0001), but not with relative humidity (P = 0.38). Logistic regression analysis, including known determinants of irritant hand dermatitis in this setting, showed that low temperature and low relative humidity tended to be risk factors (OR = 1.66 and 1.57, respectively, for the lower quartiles, P = 0.07 in both cases), and confirmed that absolute humidity significantly influenced the occurrence of irritant hand dermatitis (OR = 2.06 for < 4.8 mg/L, P < 0.01). Thus, these environmental factors must be regarded as possible confounders in the analysis of future epidemiological studies on irritant hand dermatitis and should be considered in multifactorial analyses.
Gender and Outcome in Adult Congenital Heart Disease
Authors: Carianne L. Verheugt, Cuno S.P.M. Uiterwaal, Enno T. van der Velde, Folkert J. Meijboom, Petronella G. Pieper, Hubert W. Vliegen, Arie P.J. van Dijk, Berto J. Bouma, Diederick E. Grobbee, Barbara J.M. Mulder
Journal: Circulation (2008)

Gender differences in prognosis have frequently been reported in cardiovascular disease but less so in congenital heart disease. We investigated whether gender is associated with outcome in adult patients with congenital heart disease.From the CONgenital CORvitia (CONCOR) national registry for adults with congenital heart disease, 7414 patients were identified. All outcomes before entry into the registry and during subsequent follow-up were recorded, and differences between men and women were analyzed with the underlying congenital heart defect taken into account. Median age at the end of follow-up was 35 years (range, 17 to 91 years); 49.8% were female. No gender difference in mortality was found. Women had a 33% higher risk of pulmonary hypertension (odds ratio [OR]=1.33; 95% CI, 1.07 to 1.65; P=0.01), a 33% lower risk of aortic outcomes (OR=0.67; 95% CI, 0.50 to 0.90; P=0.007), a 47% lower risk of endocarditis (OR=0.53; 95% CI, 0.40 to 0.70; P<0.001), and a 55% lower risk of an implantable cardioverter-defibrillator (OR=0.45; 95% CI, 0.26 to 0.80; P=0.006). Furthermore, the risk of arrhythmias appeared to be lower in women (OR=0.88; 95% CI, 0.77 to 1.02; P=0.08).The risk of several major cardiac outcomes in adult patients with congenital heart disease appears to vary by gender.
Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma
Authors: Evan S. Glazer, Mauro Piccirillo, Vittorio Albino, Raimondo Di Giacomo, Raffaele Palaia, Angelo A. Mastro, Gerardo Beneduce, Giuseppe Castello, Vincenzo De Rosa, Antonella Petrillo, Paolo A. Ascierto, Steven A. Curley, Francesco Izzo
Journal: Journal of Clinical Oncology (2010)

It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, alpha-fetoprotein (AFP) levels, and serum arginine levels.Eighty patients were randomly assigned to receive either 80 IU/m(2) or 160 IU/m(2) of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated.Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (+/-SE) survival for all subjects was 15.8 months (474 days +/- 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively.Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.