tbuckley/cabot-search huggingface dataset:
Procalcitonin Guidance of Antibiotic Therapy in Community-acquired Pneumonia
Authors: Mirjam Christ-Crain, Daiana Stolz, Roland Bingisser, Christian Müller, David Miedinger, Peter R. Huber, Werner Zimmerli, Stephan Harbarth, Michael Tamm, Beat Müller
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 d. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications.Objective: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia.Methods: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, after 4, 6, and 8 d, and after 6 wk.The control group (n = 151) received antibiotics according to usual practice. In the procalcitonin group (n = 151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged, less than 0.1 μg/L; discouraged, less than 0.25 μg/L; encouraged, greater than 0.25 μg/L; strongly encouraged, greater than 0.5 μg/L. The primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory, and radiographic outcome.Results: At baseline, both groups were similar regarding clinical, laboratory, and microbiology characteristics, and Pneumonia Severity Index. Procalcitonin guidance reduced total antibiotic exposure (relative risk, 0.52; 95% confidence interval, 0.48–0.55; p < 0.001), antibiotic prescriptions on admission (85 vs. 99%; p < 0.001), and antibiotic treatment duration (median, 5 vs. 12 d; p < 0.001) compared with patients treated according to guidelines. After adjustment for Pneumonia Severity Index, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2; 95% confidence interval, 2.5 to 4.2). Outcome was similar in both groups, with an overall success rate of 83%.Conclusions: Procalcitonin guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public health implications.
Temporal and spatial expression pattern of ?1 sodium channel subunit during heart development
Authors: J DOMINGUEZ, F NAVARRO, D FRANCO, R THOMPSON, A ARANEGA
Journal: Cardiovascular Research (2004)

Objectives: The aim of this study is to analyze Scn1b mRNA expression levels and protein distribution of Scn1b, a putative modulator of the pore-forming Na+ channel subunit in the heart, during mouse cardiac development. Methods: Scn1b mRNA levels were determined by real-time RT-PCR using embryonic hearts ranging from E9.5 to E18.5 as well as in postnatal and adult heart. Scn1b protein distribution and subcellular localization during cardiogenesis were analyzed by immunohistochemistry and confocal microscopy. Results: Scn1b mRNA showed a dynamic expression pattern, peaking at stage E12.5 and decreasing at E15.5. Scn1b mRNA increased at later embryonic and neonatal stages, being maximal in the adult heart. Immunohistochemistry experiments revealed comparable distribution of Scn1b protein between the different cardiac chambers at early embryonic stages. With further development, Scn1b protein showed an enhanced expression in the trabeculated myocardium and the bundle branches. At the subcellular level in later embryonic and postnatal mouse cardiomyocytes, Scn1b was present in T-tubules as identified by immunostaining of α-actinin, and in the intercalated disks as identified by immunostaining of connexin 43. Conclusion: These results demonstrate that Scn1b is expressed during mouse heart development, suggesting it can play an important role in the action potential configuration of the cardiomyocytes during heart morphogenesis.
Prognostic Factors of Sudden Sensorineural Hearing Loss in Diabetic Patients
Authors: Shuen-Fu Weng, Yuh-Shyang Chen, Tien-Chen Liu, Chuan-Jen Hsu, Fen-Yu Tseng
Journal: Diabetes Care (2004)

Sudden sensorineural hearing loss (SSNHL) is defined as the sudden onset of unilateral sensorineural hearing loss of ≥30 dB over at least three contiguous audiometric frequencies (1). Diabetes is a risk factor of SSNHL, possibly due to microangiopathy (2). Currently, the clinical studies of SSNHL rarely focus on diabetic patients. The correlations between biochemical data and hearing outcomes in SSNHL are seldom analyzed. We analyzed the characteristics of SSNHL in diabetic patients and tried to elucidate the possible prognostic factors.

Medical charts of diabetic patients admitted for SSNHL from 1984 to 2003 were retrospectively reviewed. A total of 67 patients (38 men and 29 women) with a mean …
A doxycycline-inducible urokinase receptor (uPAR) upregulates uPAR activities including resistance to anoikis in human prostate cancer cell lines
Authors: Mohammad Hasanuzzaman, Robert Kutner, Siamak Agha-Mohammadi, Jakob Reiser, Inder Sehgal
Journal: Molecular Cancer (2007)

Abstract Background The urokinase receptor (uPAR) mediates a diverse array of cellular processes including several events involved in prostate cancer metastasis. Many of these activities are initiated or enhanced by uPAR binding to its proteolytic ligand, urokinase (uPA). Our objective in this study was to generate and test an inducible lentiviral system capable of expressing uPAR and DsRed fluorescent protein in human prostate cancer cell lines. Results A DsRed-uPAR fusion construct was inserted into a lentiviral vector. Transduction of human prostate cancer cell lines with this virus and with a virus containing a reverse-tetracycline transactivator (rt-TA) resulted in a stable transgene which induced both uPAR and DsRed proteins in a dose-responsive fashion upon stimulation with doxycycline. Immunoblots and immunofluorescence studies indicated no detectable uPAR expression in non-induced prostate cancer cell lines. Cells with induced-uPAR demonstrated increased cellular adhesion to the matrix substrate vitronectin and increased net cell proliferation compared to uninduced cells. Finally, induced uPAR-expressing prostate cancer cells were resistant to anoikis over an extended time period when grown in suspension. Conclusion This doxycycline-inducible lentivirus system produces titerable levels of biologically active uPAR in vitro . This tool can be used to dissect cellular events following induction of uPAR in prostate cancer cells.
A glucocerebrosidase fusion gene in Gaucher disease. Implications for the molecular anatomy, pathogenesis, and diagnosis of this disorder.
Authors: A Zimran, J Sorge, E Gross, M Kubitz, C West, E Beutler
Journal: Journal of Clinical Investigation (1990)

The molecular diagnosis of Gaucher disease has been difficult due to the existence of several different point mutations in the glucocerebrosidase gene and due to the presence of a tightly linked, highly homologous pseudogene. We now report the occurrence of a "Lepore-like" glucocerebrosidase fusion gene in which the 5' end is the functional gene and the 3' end is the pseudogene. This further complicates the molecular diagnosis of Gaucher disease but sheds light on the molecular anatomy of the glucocerebrosidase gene complex and on the pathogenesis of this important storage disease.
High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer
Authors: Elah Pick, Yuval Kluger, Jennifer M. Giltnane, Christopher Moeder, Robert L. Camp, David L. Rimm, Harriet M. Kluger
Journal: Cancer Research (2007)

Abstract The heat shock protein HSP90 chaperones proteins implicated in breast cancer progression, including Her2/neu. HSP90-targeting agents are in clinical trials for breast cancer. HSP90 expression is high in breast cancer cell lines, yet no large studies have been conducted on expression in human tumors and the association with clinical/pathologic variables. Tissue microarrays containing 10 cell lines and primary specimens from 655 patients with 10-year follow-up were assessed using our automated quantitative analysis (AQUA) method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured HSP90 expression within the mask using Cy5-conjugated antibodies. We similarly assessed estrogen receptor, progesterone receptor, and Her2/neu expression. HSP90 expression was more variable in human tumors than in cell lines (P &amp;lt; 0.0001). High HSP90 expression was associated with decreased survival (P = 0.0024). On multivariable analysis, high HSP90 expression remained an independent prognostic marker. High HSP90 expression was associated with high Her2/neu and estrogen receptor, large tumors, high nuclear grade, and lymph node involvement. Although HSP90 levels were high in all our cell lines, expression in tumors was more variable. High HSP90 expression in primary breast cancer defines a population of patients with decreased survival. Evaluation of HSP90 expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors. [Cancer Res 2007;67(7):2932–7]
Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer's data sources
Authors: J Ruof
Journal: Annals of the Rheumatic Diseases (2003)

<b>Objective:</b> To develop a systematic set of German cost data in rheumatoid arthritis (RA) based solely on valid healthcare payer's cost data sources. <b>Methods:</b> Retrospectively one year cost data of 338 patients with RA were generated and analysed. The cost data were derived from a major statutory health insurance plan ("Allgemeine Ortskrankenkasse Niedersachsen") and the regional physicians' association ("Kassenärztliche Vereinigung Niedersachsen"). The recently published matrix of cost domains in RA was applied to structure the analysis. Descriptive statistics were used to analyse the data. <b>Results:</b> The total direct costs for the 338 patients during one year (third quarter 2000 to second quarter 2001) were €3815 per patient-year. RA related direct costs were €2312 per patient-year. Outpatient costs accounted for 73.7%, inpatient costs for 24.0%, and other disease related costs for 2.3% of RA related direct costs. Outpatients cost drivers were RA related drugs (€1019 per patient-year), physician visits (€323 per patient-year), diagnostic and therapeutic procedures and tests (€185 per patient-year), and devices and aids (€168 per patient-year). 98 patients were retired prematurely owing to RA related work disability and incurred costs of €8358 per retired patient-year. 96 patients were gainfully employed and incurred sick leave costs of €2835 per employed patient-year. <b>Conclusion:</b> Micro-costing based on healthcare payer's data provides a relatively conservative albeit highly accurate estimate of costs in RA. Both RA related and non-RA related costs must be taken into account. In gainfully employed patients and in patients who receive RA related retirement payments productivity costs exceed direct costs.
Update in Lung Cancer 2007
Authors: Sarita Dubey, Charles A. Powell
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

CHRONIC OBSTRUCTIVE PULMONARY DISEASEAs reported previously, lung cancer risk is associated with chronic obstructive pulmonary disease (COPD) (14, 15).It is not clear if this association is attributable to a shared exposure to cigarette smoke, to shared genetic susceptibility factors (16,17), and/or to facilitation of tumor initiation and promotion by (
Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types
Authors: Sarah Browall, Erik Backhaus, Pontus Naucler, Ilias Galanis, Karin Sjöström, Diana Karlsson, Stefan Berg, Joachim Luthander, Margareta Eriksson, Carl Spindler, Mikael Ejdebäck, Birger Trollfors, Jessica Darenberg, Mats Kalin, Åke Örtqvist, Rune Andersson, Birgitta Henriques-Normark
Journal: European Respiratory Journal (2014)

Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases.
Pyuria and Bacteriuria
Authors: S. R. Meadow, R. H. R. White, N. M. Johnston
Journal: BMJ (1969)

Important circumstantial evidence in support of the theory of passive dilatation of the ventricle is provided by consideration of the abnormal but characteristic ventricular cardiographic silhouettes after mitral valve replacement using low-profile disc and central-flow homograft valves.As a result of some preliminary observations we would distinguish the " turnip " heart outline that characterizes the disc valves from the " pear " heart of the homograft valve, and suggest that the shape adopted by the ventricle is determined by the grossly abnormal filling patterns in each case."It seems logical that the reduction in cardiac output that is uni- formly observed in these patients is related directly to these changes.-Iam, etc.,
Pulmonary vascular responses to exercise: a haemodynamic observation
Authors: R. Saggar, G. D. Lewis, D. M. Systrom, H. C. Champion, R. Naeije, R. Saggar
Journal: European Respiratory Journal (2012)

xercise testing provides additional information over resting variables and is a standard of care in the assessment of coronary artery disease with less subsequent cardiovascular events.In pulmonary hypertension (PH), right ventricular function is clearly an important determinant of survival.However, right ventricular impairment is currently assessed only during resting conditions.Exercise (stress) testing may provide further insight into the complex paradigm of right ventricular dysfunction, right ventricular-left ventricular interdependence and right ventricular-pulmonary artery coupling.Whether pulmonary artery pressure (Ppa)-flow relationships during exercise provides a window into earlier diagnosis of functionally significant PH or adds incrementally to our armamentarium of diagnostic tests and prognostic indicators in PH, is a topic of ongoing investigation.In this issue of the European Respiratory Journal (ERJ), the studies by KOVACS et al.[1] and WHYTE et al.[2] discuss the potential clinical utility of identifying ''normal'' and ''abnormal'' pulmonary vascular response patterns to exercise in patients aged f50 yrs.
The effects of<i>Mycobacterium vaccae</i>on allergen-induced airway responses in atopic asthma
Authors: L. Camporota, A. Corkhill, H. Long, J. Lordan, L. Stanciu, N. Tuckwell, A. Cross, J.L. Stanford, G.A.W. Rook, S.T. Holgate, R. Djukanovic
Journal: European Respiratory Journal (2003)

T-helper (Th)2 cytokines play a central role in asthma. Therefore, a double-blind randomised study was conducted to investigate whether heat-killed Mycobacterium vaccae (SRL172), a potent downregulator of Th2 cytokines, can reduce allergen-induced airway responses in patients with atopic asthma. A total 24 male asthmatics participated in this study. A bronchial allergen challenge was performed along with early (EAR) and late asthmatic responses (LAR) 2 weeks before and 3 weeks after a single intradermal injection of SRL172 or placebo. Before and after treatment, serum immunoglobulin (Ig)E levels and in vitro production of interleukin (IL)-5 by peripheral blood lymphocytes were studied. Neither treatment affected the EAR. SRL172 caused a mean 34% reduction of the area under the curve of the forced expiratory volume in one second (FEV 1 ) changes during the LAR, which failed to reach conventional statistical significance when compared with placebo. SRL172 also caused a mean 25% decrease in the maximum fall in FEV 1 during LAR, but this was not significantly different from placebo. SRL172 caused a reduction in serum IgE and IL-5 synthesis in vitro 3 weeks post-treatment (p=0.07). This study shows a trend toward significance for the effects of heat-killed Mycobacterium vaccae (SRL172) on allergen-induced airway responses. Further clinical trials, involving multiple dosing, are needed.
A phase I clinical and pharmacokinetic study of the angiogenesis inhibitor, tecogalan sodium
Authors: S G Eckhardt, H A Burris, J R Eckardt, G Weiss, G Rodriguez, M Rothenberg, D Rinaldi, R Barrington, J G Kuhn, K Masuo, K Sudo, R Atsumi, T Oguma, L Higashi, S Fields, L Smetzer, D D Von Hoff
Journal: Annals of Oncology (1996)

Tecogalan sodium is an angiogenesis inhibitor isolated from a sulfated polysaccharide produced by the bacterium Arthrobacter. The antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cellular receptors.A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-associated Kaposi's sarcoma. Patients received a single i.v. infusion every three weeks with the infusion duration ranging from one to twenty-four hours. Seven different dosage levels were studied (125, 185, 240, 300, 390, 445, and 500 mg/m2).The primary dose-limiting toxicity was prolongation of the activated partial thromboplastin time with peak times being between 1.0-4.0 times the upper limit of normal. This toxicity was ameliorated at a given dose level by prolonging the infusion time. Other common toxicities included fever (40%) and rigors (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and < 25% of unchanged drug was excreted in the urine.The recommended phase II dose of tecogalan sodium on this schedule is 390 mg/m2 over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogenesis inhibitor.
Separate effects of irradiation and of graft-versus-host reaction on rat mucosal mast cells.
Authors: A G Cummins, G H Munro, J F Huntley, H R Miller, A Ferguson
Journal: Gut (1989)

T cell mediated immune responses in the gut can produce enteropathy and malabsorption. We have investigated the relevance of mucosal mast cells (MMC) to the mechanisms of this enteropathy by using graft-versus-host reaction (GvHR) in the rat as a model of mucosal delayed type hypersensitivity. Measurements of mucosal architecture, intraepithelial lymphocytes (IEL) and MMC counts were performed in control and experimental rats, and release of rat mast cell protease II (RMCPII) into the bloodstream was used as an index of MMC activation. In unirradiated rats, jejunal MMC count was increased on day 14 of the GvHR (mean 272/mm2 v 182 in controls, p less than 0.01), as was serum RMCPII (p less than 0.01). Irradiated rats (4.5 Gy, reconstituted with isogeneic spleen cells) had low counts of IEL and crypt hyperplasia seven to 14 days after irradiation. Irradiated rats with GvHR (induced by ip injection of parental strain spleen cells) and studied on days 7, 10 and 14, had significant enteropathy with longer crypts and higher CCPR than matched irradiated animals (p less than 0.05 on day 14 when compared with irradiation alone). Intraepithelial lymphocytes counts, however, reflected only the effect of radiation. Irradiation, with or without GvHR, led to the virtual disappearance of jejunal MMC, undetectable jejunal RMCPII and very low levels of RMCPII in serum (all p less than 0.01 when compared with unirradiated controls). These experiments show that there is a modest expansion in jejunal MMC in unirradiated rats with semiallogeneic GvHR, whereas irradiation, alone or associated with GvHR, profoundly depletes MMC for at least two weeks. The enteropathy of GvHR can evolve in the virtual absence of MMC.
Refusing to be suppressed
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2005)

Refusing to be suppressedOn page 737, Fahlén et al. show that colitis-inducing effector T cells that cannot respond to the suppressive cytokine TGF-␤ refuse to be controlled by regulatory T (T reg) cells.Naturally occurring T reg cells suppress the activity of effector CD4 ϩ T cells and are essential for the prevention of autoimmune disease and chronic inflammation.TGF-␤ appears to be required for T reg cell activity, but determining which cells produce TGF-␤ and which cells respond to it has proven difficult.Fahlén and colleagues now attempt to define the role of TGF-␤ in a mouse model of T cell-induced colitis.In this model, colitis can be reversed when CD4 ϩ CD25 ϩ T reg cells are provided along with the disease-inducing effector cells.The authors showed that wild-type T reg cells inhibited the development of colitis induced by wild-type effector T cells but failed to prevent disease caused by effector T cells bearing a signaling-defective TGF-␤ receptor.This demonstrated that effector cells had to be responsive to TGF-␤ to be controlled by T reg cells.The T reg cells were not required as a source of TGF-␤ , as T reg cells from TGF-␤ -deficient mice were also able to suppress.Thus, T reg cells must be prompting another cell type to produce TGF-␤ , or may be producing a regulatory signal that operates cooperatively with TGF-␤ .But did the T reg cells also require TGF-␤ signals to induce suppression, as several previous studies had shown?The authors found no differences between the T reg populations in mice with normal or signaling-defective TGF-␤ receptors, and lymph node-derived T reg cells from both mice suppressed colitis.Transfer of splenic T reg cells with mutant TGF-␤ receptors, however, triggered rather than inhibited colitis.The authors suggest that this can be explained by contaminating effector cells that are also mutant for the TGF-␤ receptor and, therefore, cannot be controlled by the inhibitory signal.Thus, the requirement for TGF-␤ in T reg cell suppression appears to be dictated primarily by the effector cells.
Heterochromatin Protein 1 Secures Survival and Transmission of Malaria Parasites
Authors: Nicolas M.B. Brancucci, Nicole L. Bertschi, Lei Zhu, Igor Niederwieser, Wai Hoe Chin, Rahel Wampfler, Céline Freymond, Matthias Rottmann, Ingrid Felger, Zbynek Bozdech, Till S. Voss
Journal: Cell Host & Microbe (2014)