tbuckley/cabot-search huggingface dataset:
Complement component 5 contributes to poor disease outcome in humans and mice with pneumococcal meningitis
Authors: Bianca Woehrl, Matthijs C. Brouwer, Carmen Murr, Sebastiaan G.B. Heckenberg, Frank Baas, Hans W. Pfister, Aeilko H. Zwinderman, B. Paul Morgan, Scott R. Barnum, Arie van der Ende, Uwe Koedel, Diederik van de Beek
Journal: Journal of Clinical Investigation (2011)

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Disease outcome has been related to the severity of the proinflammatory response in the subarachnoid space. The complement system, which mediates key inflammatory processes, has been implicated as a modulator of pneumococcal meningitis disease severity in animal studies. Additionally, SNPs in genes encoding complement pathway proteins have been linked to susceptibility to pneumococcal infection, although no associations with disease severity or outcome have been established. Here, we have performed a robust prospective nationwide genetic association study in patients with bacterial meningitis and found that a common nonsynonymous complement component 5 (C5) SNP (rs17611) is associated with unfavorable disease outcome. C5 fragment levels in cerebrospinal fluid (CSF) of patients with bacterial meningitis correlated with several clinical indicators of poor prognosis. Consistent with these human data, C5a receptor-deficient mice with pneumococcal meningitis had lower CSF wbc counts and decreased brain damage compared with WT mice. Adjuvant treatment with C5-specific monoclonal antibodies prevented death in all mice with pneumococcal meningitis. Thus, our results suggest C5-specific monoclonal antibodies could be a promising new antiinflammatory adjuvant therapy for pneumococcal meningitis.
Effect of Increased Renal Venous Pressure on Circulatory "Autoregulation" of Isolated Dog Kidneys
Authors: S. J. G. SEMPLE, H. E. DE WARDENER
Journal: Circulation Research (1959)

The results demonstrate that autoregulation is primarily dependent on the arteriovenous pressure difference and that it is diminished or abolished when this pressure is lower than approximately 90 mm. Hg. it is suggested that in the kidney the arteriovenous pressure gradient is probably close to the true distending pressure (i.e., the transmural pressure) of the intraparenchymal renal arteries and arterioles, It is concluded that renal autoregulation is due to an active response of the muscular coats of the renal arteries and arterioles to changes in transmural pressure.
Home Delivery and Neonatal Mortality in North Carolina
Authors: Claude A. Burnett
Journal: JAMA (1980)

Neonatal mortality is examined by place and circumstances of delivery in North Carolina during 1974 through 1976 with attention given to home delivery. Planned home deliveries by lay-midwives resulted in three neonatal deaths per 1,000 live births; planned home deliveries without a lay-midwife, 30 neonatal deaths per 1,000 live births; and unplanned home deliveries, 120 neonatal deaths per 1,000 live births. The women whose babies were delivered by lay-midwives were screened in county health departments and found to be medically at low risk of complication, despite having demographic characteristics associated with high-risk of neonatal mortality. Conversely, the women delivered at home without known prenatal screening or a trained attendant had low-risk demographic characteristics but experienced a high rate of neonatal mortality. Planning, prenatal screening, and attendanttraining were important in differentiating the risk of neonatal mortality in this uncontrolled, observational study. (<i>JAMA</i>1980;244:2741-2745)
Clara cell protein as a biomarker for ozone-induced lung injury in humans
Authors: A. Blomberg, I. Mudway, M. Svensson, A. Hagenbjörk-Gustafsson, L. Thomasson, R. Helleday, X. Dumont, B. Forsberg, G. Nordberg, A. Bernard
Journal: European Respiratory Journal (2003)

Exposure to ozone (O3) impairs lung function, induces airway inflammation and alters epithelial permeability. Whilst impaired lung function and neutrophilia have been observed at relatively low concentrations, altered lung epithelial permeability is only seen after high-dose challenges. The appearance of Clara cell protein (CC16) in serum has been proposed as a sensitive marker of lung epithelial injury. Here, the use of CC16 as an injury biomarker was evaluated under a controlled exposure to O3 and the relationship between this marker of lung injury and early lung function decrements was investigated. Subjects (n=22) were exposed on two separate occasions to 0.2 parts per million O3 and filtered air for 2 h. Blood samples were drawn and lung function assessed at 2 h pre-exposure, immediately before and immediately after exposure as well as 2 and 4 h postexposure. O3 increased CC16 serum concentrations at 2 h (12.0+/-4.5 versus 8.4+/-3.1 microg x L(-1)) and 4 h postexposure (11.7+/-5.0 versus 7.9+/-2.6 microg x L(-1)) compared with air concentrations. Archived samples from O3 studies utilising the same design indicated that this increase was sustained for up to 6 h postexposure (9.1+/-2.6 versus 7.1+/-1.7 microg x L(-1)) with concentrations returning to baseline by 18 h (7.7+/-2.9 versus 6.6+/-1.7 microg x L(-1)). In these studies, the increased plasma CC16 concentration was noted in the absence of increases in traditional markers of epithelial permeability. No association was observed between increased CC16 concentrations and lung function changes. To conclude, Clara cell protein represents a sensitive and noninvasive biomarker for ozone-induced lung epithelial damage that may have important uses in assessing the health effects of air pollutants in future epidemiological and field studies.
P1069 THE EFFICACY OF ENTECAVIR IN BOTH NAIVE AND LAMIVUDINE EXPERIENCED WITHOUT RESISTANCE CHRONIC HEPATITIS B PATIENTS
Authors: S.J. Ahn, J.A. Hwang, K.B. Kim, H.J. Cho, S.S. Kim, J.Y. Cheong, S.W. Cho
Journal: Journal of Hepatology (2014)
Urinary CD80 Excretion Increases in Idiopathic Minimal-Change Disease
Authors: Eduardo H. Garin, Leila N. Diaz, Wei Mu, Clive Wasserfall, Carlos Araya, Mark Segal, Richard J. Johnson
Journal: Journal of the American Society of Nephrology (2008)

CD80 is expressed on all antigen-presenting cells and is present on podocytes in a number of experimental models of nephrotic syndrome. We tested whether urinary soluble CD80 increased with idiopathic minimal-change disease (MCD). We collected urine and serum samples from patients with MCD in relapse and in remission, patients with nephrotic syndrome resulting from other glomerular diseases (FSGS, membranoproliferative glomerulonephritis, IgA nephropathy, and membranous nephropathy), patients with systemic lupus erythematosus, and normal control subjects. Urinary concentrations of soluble CD80 in patients with relapsed MCD were significantly higher compared with those observed in patients with MCD in remission, other glomerular diseases, and systemic lupus erythematosus with and without proteinuria and healthy control subjects. Urinary concentrations of soluble CTLA-4, which is a negative regulator of CD80, were not statistically different in patients with relapsed MCD compared with those in remission. The urinary soluble CD80/CTLA-4 ratio was &gt;100-fold higher in patients with relapsed MCD compared with those in remission (<i>P</i> &lt; 0.008). In contrast, serum concentrations of soluble CD80 and CTLA-4 did not distinguish patients with MCD in relapse and in remission. In conclusion, urinary soluble CD80 is elevated in idiopathic MCD, which could be relevant to both diagnosis and pathogenesis.
Time to Clinically Significant Visual Acuity Gains after Ranibizumab Treatment for Retinal Vein Occlusion
Authors: Allen B. Thach, Linda Yau, Carol Hoang, Lisa Tuomi
Journal: Ophthalmology (2014)

To assess time to first achievement of clinically significant visual acuity (VA) gains from baseline in patients with retinal vein occlusion (RVO) receiving ranibizumab versus sham treatment.Post hoc analyses of 2 phase 3 clinical trials assessing efficacy and safety of ranibizumab in patients with branch RVO (Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety [BRAVO] study; NCT00061594) and central RVO (Ranibizumab for the Treatment of Macular Edema after Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety [CRUISE]; NCT00056836) over 12 months.Seven hundred eighty-nine patients (BRAVO, n = 397; CRUISE, n = 392).Randomization to monthly intraocular ranibizumab injections (0.3 mg/0.5 mg) or sham. After 6 monthly injections (treatment period), patients meeting prespecified criteria received as-needed (pro re nata [PRN]) ranibizumab at their assigned dose (sham patients, ranibizumab 0.5 mg) through month 12 (observation period). BRAVO patients meeting specific eligibility criteria could receive rescue laser treatment once during the treatment and once during the observation periods.Time to first gain of 15 letters or more from baseline, analyzed using Kaplan-Meier methods. To evaluate the effect of delaying ranibizumab treatment, sham patients' VA data also were analyzed, with month 6 considered as baseline to assess vision gains during the 6 months of receiving ranibizumab PRN.Median time to first 15-letter or more gain from baseline was 12.0 (sham), 4.8 (ranibizumab 0.3 mg), and 4.0 months (ranibizumab 0.5 mg) in BRAVO and 12.2, 5.9, and 5.2 months, respectively, in CRUISE. The cumulative proportion of patients who had ever gained 15 letters or more from baseline by month 12 was 50% (sham), 68% (ranibizumab 0.3 mg), and 71% (ranibizumab 0.5 mg) in BRAVO and 42%, 61%, and 66%, respectively, in CRUISE. After 6 months of ranibizumab PRN treatment, a cumulative 10.8% (BRAVO) and 26.2% (CRUISE) of initially sham-treated patients ever gained 15 letters or more.This retrospective analysis shows that more than 50% of patients treated with monthly ranibizumab achieved clinically significant vision gains during the initial 6 months of treatment, which largely were maintained using PRN treatment to 12 months. In comparison, less than 50% of patients initially randomized to sham (and later receiving ranibizumab 0.5 mg PRN treatment) ever achieved clinically significant vision gains. These results suggest that initiating treatment immediately after diagnosis may provide the greatest vision gains. The potential benefits of early treatment should be evaluated further in prospective clinical studies.
THE BEHAVIOR CHART IN MENTAL DISEASES
Authors: EDWARD J. KEMPF
Journal: American Journal of Psychiatry (1915)

Conclusion.—The striking dissimilarity of the curves plotted for the various psychoses suggests that after further data are accumulated, suitable points isolated, and arranged in the most comprehensive series for the problems to be covered, perhaps a chart may be constructed which will aid materially in the classification of cases. Certainly the record of the case can only become more interesting and better clarified by an accurate chart record appended to the case history. Additional facts about behavior may also be gathered which will give us more insight into the more obscure biological principles determining behavior.
A single five minute period of rapid atrial pacing fails to limit infarct size in the in situ rabbit heart
Authors: M. S Marber, D. M Walker, D. J Eveson, J M. Walker, D. M Yellon
Journal: Cardiovascular Research (1993)

Objective: Rapid pacing has been shown to precondition the dog heart against ischaemic dysrhythmia. The aim of this study was to determine whether rapid pacing could also limit infarct size. Methods: Rabbits (n=5) were rapidly paced via the left atrium at 420-480 beats·min−1. Five min of rapid pacing and 10 min of recovery in sinus rhythm were followed by 45 min of regional ischaemia and 120 min of reperfusion. Control rabbits (n=9) were treated identically without prior rapid pacing. Infarct size was determined in both groups using tetrazolium and expressed as a percentage of the area at risk demarcated by fluorescent miscrospheres. In a separate series of experiments, rapidly paced Langendorff perfused rabbit hearts (n=9) were used to determine coronary flow under perfusion conditions designed to simulate the in vivo situation during rapid pacing. Results: Rapid pacing caused a fall in systolic pressure from 91.4(SEM 4.5) to 47.0(5.9) mm Hg (p<0.01) and diastolic pressure from 67.2(2.9) to 23.6(3.2) mm Hg (p<0.01). Both recovered within 30 s of cessation of pacing. During rapid pacing the action potential duration shortened from 192(13) to 128(5) ms (p=0.01) and developed electrical alternans (n=4). Following rapid pacing the ECG showed either ST depression or T wave inversion (n=4). Despite these profound changes, rapid pacing did not reduce infarct size v control [52.7(4.6)% v 60.8(9.1)% of the area at risk, respectively]. The in vitro experiments estimated that rapid pacing would result in a reduction in coronary flow to 44% of that in sinus rhythm without a significant rise in lactate efflux. Conclusions: In our model, pretreatment with rapid pacing fails to reduce infarct size. The most likely reason for this is that rapid pacing at a rate of 480 beats·min−1 does not cause myocardial ischaemia of sufficient severity to trigger the preconditioning response. Cardiovascular Research 1993;27:597-601
Focal Adhesion Kinase Is Involved in Angiotensin II–Mediated Protein Synthesis in Cultured Vascular Smooth Muscle Cells
Authors: Geetha Govindarajan, Diane M. Eble, Pamela A. Lucchesi, Allen M. Samarel
Journal: Circulation Research (2000)

Abstract —The rate of vascular smooth muscle cell protein synthesis and cellular hypertrophy in response to angiotensin II (Ang II) is dependent on activation of protein tyrosine kinases (PTKs) and both the extracellular signal–regulated kinase (ERK) 1/2 and p70 S6K pathways. One potential PTK that may regulate these signaling cascades is focal adhesion kinase (FAK), a nonreceptor PTK associated with focal adhesions. We used an actin depolymerizing agent, cytochalasin D (Cyt-D), and a replication-defective adenovirus encoding FAK-related nonkinase (FRNK), an inhibitor of FAK-dependent signaling, as tools to assess whether FAK was upstream of the ERK1/2 and/or the p70 S6K pathways. Cyt-D reduced basal FAK phosphorylation and blocked Ang II–dependent FAK phosphorylation in a dose-dependent manner. Confocal microscopy indicated that Cyt-D induced actin filament disruption and FAK delocalization from focal adhesions. Cyt-D also reduced Ang II–induced ERK1/2 activation, but p70 S6K activation was relatively unaffected. Cyt-D reduced basal protein synthetic rate and substantially reduced the Ang II–induced increase in protein synthesis. Similarly, FRNK overexpression blocked Ang II–induced FAK phosphorylation and ERK1/2 activation, but not p70 S6K phosphorylation, and markedly inhibited protein synthesis. This is the first report to demonstrate that FAK is a critical component of the signal transduction pathways that mediate Ang II–induced ERK1/2 activation, c- fos induction, and enhanced protein synthesis in vascular smooth muscle cells.
Association between Younger Age When First Overweight and Increased Risk for CKD
Authors: Richard J. Silverwood, Mary Pierce, Claudia Thomas, Rebecca Hardy, Charles Ferro, Naveed Sattar, Peter Whincup, Caroline Savage, Diana Kuh, Dorothea Nitsch
Journal: Journal of the American Society of Nephrology (2013)

There is little information on how the duration of overweight or obesity during life affects the risk for CKD. To investigate whether prolonged exposure to overweight during adult life increases the risk of later CKD in a cumulative manner, we analyzed data from the Medical Research Council National Survey of Health and Development, a socially stratified sample of 5362 singleton children born in 1 week in March 1946 in England, Scotland, and Wales. Multiple imputation expanded the analysis sample from the initial 1794 participants with complete data to 4584. This study collected self-reported body mass index (BMI) at ages 20 and 26 years and measured BMI at ages 36, 43, 53, and 60–64 years. The outcome of interest was CKD at age 60–64 years, suggested by estimated GFR (eGFR) <60 ml/min per 1.73 m2 and/or urine albumin-to-creatinine ratio (UACR) ≥3.5 mg/mmol. In analyses adjusted for childhood and adulthood social class, first becoming overweight at younger ages was associated with higher odds of developing CKD by age 60–64 years. Compared with those who first became overweight at age 60–64 years or never became overweight, those first overweight at age 26 or 36 years had approximately double the odds of developing CKD. The strength of this association decreased with increasing age when first overweight (P for trend <0.001). These associations were consistent for creatinine-based eGFR, cystatin C–based eGFR, and UACR. Taken together, these results suggest that preventing overweight in early adulthood may have a considerable effect on the prevalence of CKD in the population.
High Innate Production Capacity of Proinflammatory Cytokines Increases Risk for Death from Cancer: Results of the PROSPER Study
Authors: Stella Trompet, Anton J.M. de Craen, Simon Mooijaart, David J. Stott, Ian Ford, Naveed Sattar, Wouter Jukema, Rudi G.J. Westendorp
Journal: Clinical Cancer Research (2009)

PURPOSE: Various lines of evidence suggest that proinflammatory factors may play a role in tumor growth and metastasis, the leading cause of cancer-related mortality. However, most evidence originates from animal models, only few human studies reported an association between proinflammatory cytokines and death from cancer. Here, we investigated the association between circulating levels and innate production capacity of proinflammatory cytokines and cancer incidence and mortality in the PROspective Study on Pravastatin in the Elderly at Risk (PROSPER). EXPERIMENTAL DESIGN: Circulating levels of interleukin 6 (IL-6) and C-reactive protein were measured in all 5,804 participants of the PROSPER study. The innate production capacity of IL-6, IL-1beta, and tumor necrosis factor alpha (TNF-alpha) were measured in a random sample of 403 subjects. RESULTS: We showed that high circulating inflammatory markers were associated with an increased risk for cancer incidence and death from cancer during follow-up (all P < 0.05). Moreover, high innate proinflammatory cytokine production capacity is associated with an increased risk for death from cancer (all P < 0.04) but not with higher cancer incidence during follow-up (all P > 0.6). CONCLUSIONS: High innate production capacity of proinflammatory cytokines is associated with an increased risk for death from cancer, probably because of increased tumor growth and metastasis. Because there was no association between innate production capacity and cancer incidence, the association between circulating levels and cancer incidence at least partially reflects reversed causality. (Clin Cancer Res 2009;15(24):7744-8).
Ankylosing Spondylitis, Psoriatic Arthritis, and Risk of Malignant Lymphoma: A Cohort Study Based on Nationwide Prospectively Recorded Data From Sweden
Authors: K. Hellgren, K. E. Smedby, C. Backlin, C. Sundstrom, N. Feltelius, J. K. Eriksson, E. Baecklund, J. Askling
Journal: Arthritis & Rheumatology (2014)

Data on lymphoma risk in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are scarce. This study was undertaken to assess the risk of lymphoma in AS and PsA overall and in relation to therapies, including tumor necrosis factor inhibitor (TNFi), for which lymphoma risks are a concern.Through the Swedish National Patient Register we assembled nationwide prevalence cohorts of patients with AS (n = 8,707) and patients with PsA (n = 19,283) for whom data were obtained between 2001 and 2010. Each cohort member was matched to 5 population comparator subjects. Linkage with the nationwide Cancer Register identified all lymphomas recorded from 2001 to 2010. Through the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]), we identified patients exposed to TNFi in the AS cohort (n = 1,908) and the PsA cohort (n = 2,605) before lymphoma diagnosis. Hazard ratios (HRs) for lymphoma were estimated by Cox regression. Crude incidences of lymphoma in TNFi-exposed and TNFi-naive patients were compared.For AS patients, the HR of having lymphoma versus the general population was 0.9 (95% confidence interval [95% CI] 0.5-1.6) (14 lymphomas). For PsA patients, the corresponding HR was 1.2 (95% CI 0.9-1.7) (45 lymphomas). For PsA patients treated with methotrexate and/or sulfasalazine, the HR of having lymphoma was 1.7 (95% CI 1.0-3.1). The numbers and incidence of lymphoma were not materially different in TNFi-exposed versus TNFi-naive AS and PsA patients, although the numbers of lymphomas were small.In contrast to rheumatoid arthritis, the average risks of lymphoma in AS or PsA are not elevated, although increased risks in a subset of PsA patients cannot be excluded. Our findings indicate that TNFi does not affect the risk of lymphoma in AS or in PsA.
Multi-parametric MRI – ultrasound fusion targeted biopsies using varian brachytherapy software: A practical solution to deliver targeted biopsies
Authors: David Eldred-Evans, Paul Sturch, Kathy Duong, Janette Kinsella, Mark McGovern, Andrew Robinson, Alex Polson, Ashish Chandra, Giles Rottenburg, Stephen Morris, Rick Popert
Journal: International Journal of Surgery (2013)
Airflow limitation due to COPD despite tuberculosis sequellae
Authors: Nawel Ben Salem, Nawel Chaouch, Manel Loukil, Mourad Zarrouk, Sana Cheikh Rouhou, Hajer Racil, Khaoula Ben Miled, Abdellatif Chabbou
Journal: European Respiratory Journal (2011)

Pulmonary (P) tuberculosis (TB) and COPD are both a significant worldwide burden in terms of morbidity and mortality. They can both induce similar respiratory symptoms and chronic air flow limitation (AFL) leading to diagnosis difficulties.  To clarify if COPD can be considered in patients with TB sequellae, we retrospectively analyzed cases of patients with AFL (FEV1/VC post bronchodilator   Fifteen patients were included. Mean age was 60 years (44-83 years). Mean smoking level was 58 pack year. The mean delay between TB history and diagnosis of COPD was 20 years. Dyspnea was present in all cases and associated to chronic cough and sputum in 87% of cases. CT scan showed besides TB sequellae, P emphysema in all cases (centrolobular in 75%). AFL was severe in 80% of cases (GOLD III and IV). Treatment was based on theophylline and/or inhaled long-acting B2 agonists in all cases. All patients had clinical improvement with bronchodilator. Outcome was marked by at least one exacerbation for 13 patients due to P embolism in 2 cases, pneumothorax in 1 case and respiratory infections in all other cases.  COPD should be considered in smokers with AFL even if they have a previous history of PTB. Despite few cases of paraseptal emphysema, the majority of these patients show predominant P centrolobular and panlobular emphysema with an outcome similar to those with COPD and no PTB history.