tbuckley/cabot-search huggingface dataset:
Comparative validation of prognostic rules for community-acquired pneumonia in an elderly population
Authors: S Ewig, T Kleinfeld, T Bauer, K Seifert, H Schafer, N Goke
Journal: European Respiratory Journal (1999)

The aim of the study was to validate the prediction rule of M.J. Fine and coworkers for clinical outcome variables and three prognostic rules for the individual outcome of community-acquired pneumonia in an elderly population (rule 1: respiratory frequency > or =30 breaths x min(-1), diastolic blood pressure < or =60 mmHg, blood urea nitrogen >7 mM; rule 2: respiratory frequency > or =30 breaths x min(-1), diastolic blood pressure < or =60 mmHg, mental confusion; and rule 3: systolic blood pressure < or =80 mmHg, cardiac frequency > or =90 beats x min(-1), lactate dehydrogenase activity > or =260 IU x L(-1); death was predicted in the presence of at least two of three parameters). Overall 168 consecutive episodes of community-acquired pneumonia in patients aged > or =65 yrs and hospitalized in a primary care hospital were studied prospectively. Fine's rule was tested for its ability to predict length of hospital stay, requirement for intensive care unit (ICU) admission and death. For the three prognostic rules of individual outcome, performance regarding predicting death was determined. Mortality was 17/168 (10%). Fine's rule accurately predicted length of stay, the requirement for ICU admission and the risk of death from pneumonia as compared to the original derivation and validation cohorts. All three rules achieved moderate-to-high specificity (73%, 88% and 80%, respectively) and high negative predictive values (95%, 94% and 93%, respectively) but had a low sensitivity (65%, 47% and 47%, respectively). Rule 2 most closely reflected the risk of death from pneumonia when Fine's classification was used as reference. Fine's rule proved to give valid estimations regarding clinical outcome variables of community-acquired pneumonia in the elderly. The prognostic rules may be useful in determining individual patients at lower risk of death caused by pneumonia.
Surgery versus Prolonged Conservative Treatment for Sciatica
Authors: Wilco C. Peul, Hans C. van Houwelingen, Wilbert B. van den Hout, Ronald Brand, Just A.H. Eekhof, Joseph T.J. Tans, Ralph T.W.M. Thomeer, Bart W. Koes
Journal: New England Journal of Medicine (2007)

Lumbar-disk surgery often is performed in patients who have sciatica that does not resolve within 6 weeks, but the optimal timing of surgery is not known.We randomly assigned 283 patients who had had severe sciatica for 6 to 12 weeks to early surgery or to prolonged conservative treatment with surgery if needed. The primary outcomes were the score on the Roland Disability Questionnaire, the score on the visual-analogue scale for leg pain, and the patient's report of perceived recovery during the first year after randomization. Repeated-measures analysis according to the intention-to-treat principle was used to estimate the outcome curves for both groups.Of 141 patients assigned to undergo early surgery, 125 (89%) underwent microdiskectomy after a mean of 2.2 weeks. Of 142 patients designated for conservative treatment, 55 (39%) were treated surgically after a mean of 18.7 weeks. There was no significant overall difference in disability scores during the first year (P=0.13). Relief of leg pain was faster for patients assigned to early surgery (P<0.001). Patients assigned to early surgery also reported a faster rate of perceived recovery (hazard ratio, 1.97; 95% confidence interval, 1.72 to 2.22; P<0.001). In both groups, however, the probability of perceived recovery after 1 year of follow-up was 95%.The 1-year outcomes were similar for patients assigned to early surgery and those assigned to conservative treatment with eventual surgery if needed, but the rates of pain relief and of perceived recovery were faster for those assigned to early surgery. (Current Controlled Trials number, ISRCTN26872154 [controlled-trials.com].).
Dual role of α-defensin-1 in anti–HIV-1 innate immunity
Authors: Theresa L. Chang, Jesus Vargas, Armando DelPortillo, Mary E. Klotman
Journal: Journal of Clinical Investigation (2005)

Alpha-defensins are abundant antimicrobial peptides in polymorphonuclear leukocytes and play an important role in innate immunity. We have previously shown that alpha-defensin-1 can inhibit HIV-1 replication following viral entry. Here we examined the molecular mechanism(s) of alpha-defensin-1-mediated HIV-1 inhibition. Alpha-defensin-1 had a direct effect on HIV-1 virions at a low MOI in the absence of serum. The direct effect on HIV-1 virions was abolished by the presence of serum or an increase in virus particles. Studying the kinetics of the HIV life cycle revealed that alpha-defensin-1 inhibited steps following reverse transcription and integration. Analysis of PKC phosphorylation in primary CD4+ T cells in response to alpha-defensin-1 indicated that alpha-defensin-1 inhibited PKC activity. Pretreatment of infected CD4+ T cells with a PKC activator, bryostatin 1, partially reversed alpha-defensin-1-mediated HIV inhibition. Like alpha-defensin-1, the PKC isoform-selective inhibitor Go6976 blocked HIV-1 infection in a dose-dependent manner. Furthermore, kinetic studies and analysis of HIV-1 products indicated that alpha-defensin-1 and Go6976 blocked HIV-1 infection at similar stages in its life cycle, including nuclear import and transcription. Taken together, our studies demonstrate that, in the absence of serum, alpha-defensin-1 may act directly on the virus, but, in the presence of serum, its effects are on the cell, where it inhibits HIV-1 replication. At least 1 of the cellular effects associated with HIV inhibition is interference with PKC signaling in primary CD4+ T cells. Studying the complex function of alpha-defensin-1 in innate immunity against HIV has implications for prevention as well as therapeutics.
Targeting Cancer with Bugs and Liposomes: Ready, Aim, Fire
Authors: Ian Cheong, Xin Huang, Katherine Thornton, Luis A. Diaz, Shibin Zhou
Journal: Cancer Research (2007)

Abstract One of the major challenges facing cancer therapy today is achieving specificity. Current efforts to meet this challenge are focused on developing targeted therapeutics specific to the cancer cell. An alternative approach is to selectively deliver cytotoxic agents to the tumor site. With this end in mind, liposomes optimized for physical robustness have been developed and used clinically as drug delivery vehicles. Paradoxically, the effectiveness of these liposomes is hampered by the suboptimal release of bioavailable drug. This article will highlight the recent advance in using a novel lipase secreted by the tumor-colonizing anaerobic bacterium Clostridium novyi-NT to induce the targeted release of liposomal payloads within tumors. [Cancer Res 2007;67(20):9605–8]
Brain metastatic recurrence following radically treated lung cancer; a retrospective analysis
Authors: Ali Al-Ameri, Matthew Callister
Journal: European Respiratory Journal (2014)

Background

There is limited evidence estimating rates of brain metastatic recurrence following radical treatment of lung cancer. This study sought to determine brain recurrence rate of lung cancer in a large teaching hospital in the UK.

Method

722 cases with radically treated lung cancer over a five-year period (2008-2012) were reviewed. Parameters recorded included stage (TNM7 for 2010 onwards), treatment modality, cell type and dates of treatment, brain recurrence and death.

Results

92 (13%) had brain imaging before radical treatment. 222 (30%) had brain imaging prompted by symptoms in post-radical treatment follow-up. 49 (6.8%) had confirmed brain metastases by either contrast enhanced CT head or MR brain. Rates of brain metastases by original stage were: IA 2.8%, IB 5.0%, IIA 5.3%, IIB 9.2%, IIIA 12.5, IIIB 8.7% and IV 27.8%. Rate by histological subtype were squamous 3.7%, adenocarcinoma 5.4%, non-small cell not otherwise specified 10.9%, large cell 13.2% and small cell 15.6%. A Kaplan-Meier curve for brain metastatic recurrence is shown in figure 1 (censored by patient death or abbreviated follow-up).

![Figure][1] 



Conclusion

Approximately 1 in 10 radically treated patients will relapse with brain metastases over the 3 years following treatment. Rate of brain metastatic recurrence of lung cancer is closely related to the stage at the time of radical treatment, and histological subtype.

 [1]: pending:yes
High Density Lipoprotein (HDL) Reduces Renal Ischemia/Reperfusion Injury
Authors: Christoph Thiemermann, Nimesh S.A. Patel, Espen O. Kvale, Gillian W. Cockerill, Paul A.J. Brown, Keith N. Stewart, Salvatore Cuzzocrea, Domenico Britti, Helder Mota-Filipe, Prabal K. Chatterjee
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. High-density lipoproteins (HDL) have been shown to reduce organ injury and mortality in animal models of shock via modulation of the expression of adhesion molecules and pro-inflammatory enzymes. As renal inflammation plays an important role in the development of ischemia/reperfusion (I/R) injury of the kidney, the aim of this study was to investigate the ability of HDL to alleviate renal dysfunction and injury in a rat model of renal I/R. HDL (80 mg/kg, intravenous) was administered to male Wistar rats 30 min before bilateral renal ischemia for 45 min followed by reperfusion for up to 48 h. After 6-h reperfusion, HDL significantly reduced (1) renal and tubular dysfunction, (2) tubular and reperfusion-injury, and (3) histologic evidence of renal injury. HDL also improved renal function (after 24-h and 48-h reperfusion) and reduced histologic signs of renal injury (after 48-h reperfusion). Administration of HDL significantly reduced the numbers of polymorphonuclear leukocytes (PMN) infiltrating into renal tissues during reperfusion, which was reflected by an attenuation of the increase in renal myeloperoxidase activity caused by I/R. Furthermore, HDL markedly reduced expression of the adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), and P-selectin during reperfusion. The increase in renal malondialdehyde levels caused by renal I/R was also significantly reduced by HDL, suggesting attenuation of lipid peroxidation subsequent to oxidative stress. These results demonstrate that HDL significantly reduces renal I/R injury and severity of ischemic acute renal failure. It is proposed that the mechanism of protection involves reduction of the expression of adhesion molecules, resulting in reduction of PMN infiltration and oxidative stress. E-mail: [email protected]
Wound healing on the lower leg after radiotherapy or cryotherapy of Bowen's disease and other malignant skin lesions
Authors: N. H. COX, P. DYSON
Journal: British Journal of Dermatology (2006)

To investigate lower leg wound healing after treatment of skin tumours, the results of external beam radiotherapy were assessed for 141 lesions in 91 patients. Poor healing or failure to heal occurred in 33%, and was related to the age of the patients, the diameter of the radiotherapy field, and the dose and energy of radiotherapy used. No effect of fractionation on healing was apparent, but only 14% of patients were exposed to regimens with a nominal standard dose of over 1800 rets. Age > 90 years, field diameter > 4 cm and dose > 3000 cGy were all associated with a risk of impaired healing of over 50%. The most frequent single diagnosis (59 lesions) in the radiotherapy patients was Bowen's disease. The results of wound healing in these patients were compared with the results of cryotherapy to 82 lower leg Bowen's disease lesions in 49 dermatology patients. Only 2% of the cryotherapy lesions failed to heal compared with 20% of the radiotherapy wounds, although 6% of cryotherapy cases had local recurrence compared with none in the radiotherapy group. Serial overlapping cryotherapy fields of up to 2 cm diameter were shown to be a valid treatment option for Bowen's disease, as no patients had therapy-related failure to heal. To avoid the requirement for potentially more difficult post-radiotherapy salvage surgery, intra-epidermal non-invasive skin tumours > 4 cm in diameter on the lower leg are probably initially best treated by a primary surgical procedure or by staged cryotherapy. Invasive carcinoma of > 4 cm diameter is best treated by surgical excision.(ABSTRACT TRUNCATED AT 250 WORDS)
Influence of Renal Function on the Efficacy and Safety of Fondaparinux Relative to Enoxaparin in Non–ST-Segment Elevation Acute Coronary Syndromes
Authors: Keith A.A. Fox
Journal: Annals of Internal Medicine (2007)

Background: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. Objective: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. Design: Subgroup analysis of a randomized, controlled trial. Setting: Patients presenting to the hospital with non–ST-segment elevation ACS. Patients: 19 979 of the 20 078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. Measurements: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. Results: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. Conclusions: The benefits of fondaparinux over enoxaparin when administered for non–ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.
Exercise training prevents maturation-induced decreases in insulin receptor substrate-1 and phosphatidylinositol 3-kinase in rat skeletal muscle
Authors: Masaru Nagasaki, Naoya Nakai, Yoshiharu Oshida, Zhihao Li, Ming Xu, Mariko Obayashi, Taro Murakami, Atsushi Yoshimura, Noriaki Fujitsuka, Yoshiharu Shimomura, Yuzo Sato
Journal: Metabolism (2000)
The <i>Tbx2</i> <sup>+</sup> Primary Myocardium of the Atrioventricular Canal Forms the Atrioventricular Node and the Base of the Left Ventricle
Authors: Wim T.J. Aanhaanen, Janynke F. Brons, Jorge N. Domínguez, M. Sameer Rana, Julia Norden, Rannar Airik, Vincent Wakker, Corrie de Gier-de Vries, Nigel A. Brown, Andreas Kispert, Antoon F.M. Moorman, Vincent M. Christoffels
Journal: Circulation Research (2009)

The primary myocardium of the embryonic heart, including the atrioventricular canal and outflow tract, is essential for septation and valve formation. In the chamber-forming heart, the expression of the T-box transcription factor Tbx2 is restricted to the primary myocardium. To gain insight into the cellular contributions of the Tbx2+ primary myocardium to the components of the definitive heart, genetic lineage tracing was performed using a novel Tbx2Cre allele. These analyses revealed that progeny of Tbx2+ cells provide an unexpectedly large contribution to the Tbx2-negative ventricles. Contrary to common assumption, we found that the embryonic left ventricle only forms the left part of the definitive ventricular septum and the apex. The atrioventricular node, but not the atrioventricular bundle, was found to derive from Tbx2+ cells. The Tbx2+ outflow tract formed the right ventricle and right part of the ventricular septum. In Tbx2-deficient embryos, the left-sided atrioventricular canal was found to prematurely differentiate to chamber myocardium and to proliferate at increased rates similar to those of chamber myocardium. As a result, the atrioventricular junction and base of the left ventricle were malformed. Together, these observations indicate that Tbx2 temporally suppresses differentiation and proliferation of primary myocardial cells. A subset of these Tbx2Cre-marked cells switch off expression of Tbx2, which allows them to differentiate into chamber myocardium, to initiate proliferation, and to provide a large contribution to the ventricles. These findings imply that errors in the development of the early atrioventricular canal may affect a much larger region than previously anticipated, including the ventricular base.
Role of Cyclins in Epithelial Response to Oxidants
Authors: ANNICK CLEMENT, ALEXANDRA HENRION-CAUDE, VALERIE BESNARD, SOPHIE CORROYER
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Section:ChooseTop of pageAbstract <<CELL CYCLE CONTROLEPITHELIAL CELL RESPONSE ...CONCLUSIONReferencesCITING ARTICLES
Helicobacter pylori antimicrobial resistance rates in the central region of Portugal
Authors: N. Almeida, J.M. Romãozinho, M.M. Donato, C. Luxo, O. Cardoso, M.A. Cipriano, C. Marinho, A. Fernandes, C. Calhau, C. Sofia
Journal: Clinical Microbiology and Infection (2014)
PROTHROMBIN DEFICIENCY THE CAUSE OF BLEEDING IN BILE FISTULA DOGS
Authors: W. B. Hawkins, K. M. Brinkhous
Journal: The Journal of Experimental Medicine (1936)

The bleeding tendency that develops in bile fistula dogs, completely or partially deprived of bile, is due to a prothrombin deficiency of the blood plasma. However, a relatively low prothrombin level may exist in these animals without the occurrence of spontaneous hemorrhage. The prothrombin level may remain within the limits of normal if sufficient bile has been fed. In these cases no disturbance in blood clotting occurs.
THE DIGESTIBILITY OF BACTERIA
Authors: C. E. Dukes
Journal: BMJ (1922)

r THcE BMWkus= 430 I ~~~~~~~~~~~~~~~~~~~~~~~~~~ Control tlhere were over 12,000 registered mental defectives, including criminal and non-criminal.Certainly iny suggestion is more hlumiane than that of Plato, wlho, whilst not being opposed to marriages, wished that the offspring of the least worthly should not be reared; or of Aristotle, wlho was in favour of allowing children in excess of tllose required to die from exposure, and tllat all deformned clhildren slhould not be permitted to live.In conclusioln, I may say first, that, as the mortality amongst illegitimate clhildreni is so great, it would be an advantage if an effort were made to save some of tlleir lives, and if phlilanthropic arrangetnents could be inaugurated for brinaina them up iu healtlly surroundings, so that they migbt eventually become of service to tlle State.Secondly, that lookina to the amount of sterility, and the enormous loss of life caused respectively by gonorrlloea and sypllilis, it is urgently desirable tllat notification of these diseases slhould be rendered compulsory.Thirdly, tlhat, as I have pointed out, we lhave a distinct fall in tlle birtli rate; that by tlle widespread adoption of contraceptives, wllich from a plhvsiological point of view cannot be approved, but wlliclh we are certain will be ever increasingly used, we rmlust not expect an average of more than two birtlhs from eachimarriage-possibly only one; tlhat, as we know from a mnost conservative estimate there must be at least four cliildren per marriage arnongst families wlho can produce children, allowing for infantile mortality, tllose -who never nmarry, and those wlho are unfit to produce children, we cannot anticipate a real increase in the population.23It follows, tllerefore, that our country is faced in thle future with the problem of race suicide.Anid lastly, should my suggestion of the granting of a State certificate of marriage be adopted, we shlould lhave the satisfaction of ktnowing thlat in future our profession would be tlhe means of lhelping to compensate for loss of numbers by ensuring for the State the advent of healthy children-the best and surest evidence of a virile race.
THE CHEMOSUPPRESSION OF CHEMOTAXIS
Authors: Peter A. Ward
Journal: The Journal of Experimental Medicine (1966)

The effects of various drugs on chemotaxis of polymorphonuclear leukocytes (PMN's) in vitro and in vivo have been studied. Response of rabbit PMN's in vitro to the chemotactic factor of rabbit serum, consisting of an activated protein-protein complex of the fifth and sixth (and probably seventh) components of complement (C'), is suppressed by hydrocortisone, methyl prednisolone, and chloroquine. Drug concentrations causing 50% inhibition of chemotaxis in vitro were found to be: hydrocortisone, 2.9 x 10(-4)M; methly prednisolone, 1.2 x 10(-4)M; and chloroquine 8.5 x 10(-6)M. The hydrocortisone effect on PMN's appeared to be irreversible, since washing of the cells did not restore their chemotactic response. 2, 4-Dinitrophenol (DNP), vitamin A, and endotoxin did not inhibit chemotaxis. Hydrocortisone and chloroquine did block serum C' activity in vitro, but only at substantially higher concentrations. Using the reversed passive Arthus reaction in guinea pigs as a model for chemotaxis in vivo, systemic treatment of animals with hydrocortisone or chloroquine inhibited development of the vasculitis. Circulating antigen and C' were fixed in vascular structures, and serum C' was not perceptibly altered. Nevertheless, PMN infiltrates failed to occur. Local administration of hydrocortisone also prevented influx of PMN's in the Arthus reaction, in spite of the fact that immune reactants were found fixed in the vascular walls. Systemic treatment of guinea pigs with DNP did not diminish the intensity of the Arthus reactions. Phagocytosis of zymosan particles by rabbit PMN's was inhibited by hydrocortisone, methyl prednisolone, and chloroquine, but not by DNP or endotoxin. The concentrations of drugs inhibitory in phagocytosis were substantially higher than those required for inhibition of chemotaxis in vitro. These findings suggest that hydrocortisone and chloroquine inhibit the inflammatory process by preventing the response of leukocytes to chemotactic stimuli.