tbuckley/cabot-search huggingface dataset:
Classifying AKI by Urine Output versus Serum Creatinine Level
Authors: John A. Kellum, Florentina E. Sileanu, Raghavan Murugan, Nicole Lucko, Andrew D. Shaw, Gilles Clermont
Journal: Journal of the American Society of Nephrology (2015)

Severity of AKI is determined by the magnitude of increase in serum creatinine level or decrease in urine output. However, patients manifesting both oliguria and azotemia and those in which these impairments are persistent are more likely to have worse disease. Thus, we investigated the relationship of AKI severity and duration across creatinine and urine output domains with the risk for RRT and likelihood of renal recovery and survival using a large, academic medical center database of critically ill patients. We analyzed electronic records from 32,045 patients treated between 2000 and 2008, of which 23,866 (74.5%) developed AKI. We classified patients by levels of serum creatinine and/or urine output according to Kidney Disease Improving Global Outcomes staging criteria for AKI. In-hospital mortality and RRT rates increased from 4.3% and 0%, respectively, for no AKI to 51.1% and 55.3%, respectively, when serum creatinine level and urine output both indicated stage 3 AKI. Both short- and long-term outcomes were worse when patients had any stage of AKI defined by both criteria. Duration of AKI was also a significant predictor of long-term outcomes irrespective of severity. We conclude that short- and long-term risk of death or RRT is greatest when patients meet both the serum creatinine level and urine output criteria for AKI and when these abnormalities persist.
Future prospects for anti-cytokine treatment
Authors: Marc Feldmann, Jadwiga Miotla, Ewa Paleolog, Richard Williams, Anne-Marie Malfait, Peter Taylor, Fionula M Brennan, Ravinder N Maini
Journal: Annals of the Rheumatic Diseases (2000)

The era of anti-cytokine treatment in rheumatology has just begun. The first generation therapeutic agents, biological agents that block tumour necrosis factor alpha such as monoclonal antibodies or receptor Ig fusion proteins are safe and effective, and so this has generated much interest in how to increase the benefit or deliver it more cost effectively. This article provides a personal view of the coming trends in anti-cytokine treatment. Which of these will be realised in the future will be of interest.
Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents
Authors: Ahcène Boumendjel, Hélène Baubichon‐Cortay, Doriane Trompier, Thomas Perrotton, Attilio Di Pietro
Journal: Medicinal Research Reviews (2005)

Multidrug resistance protein 1 (MRP1) belongs to the ATP-binding cassette (ABC) transporter family. It is able to transport a broad range of anticancer drugs through cellular membranes, thus limiting their antiproliferative action. Since its discovery in 1992, MRP1 has been the most studied among MRP proteins, which now count nine members. Besides the biological work, which targets structure elucidation, binding sites location, and mode of action, most efforts have been focused on finding molecules which act as MRP1 inhibitors. In this review, we attempt to summarize and highlight studies dealing with modulators of MRP1-mediated multidrug resistance (MDR), which have been accomplished in the last 5 years. The reported MRP1 inhibitors are discussed according to their chemical class. Finally, we try to bring information on structure-activity relationship (SAR) aspects and how modulators might interact with MRP1. This study may facilitate the rational design of future modulators of MDR.
The Koebner phenomenon and AIDS-related Kaposi's sarcoma
Authors: P.D. French, J.R.W. Harris, D.E. Mercey
Journal: British Journal of Dermatology (1994)

Journal Article The Koebner phenomenon and AIDS‐related Kaposi's sarcoma Get access P.D. French, P.D. French Department of Genitourinary Medicine, The Middlesex Hospital, Mortimer Street, London W1 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar J.R.W. Harris, J.R.W. Harris Department of Genitourinary Medicine, St Mary's Hospital, Praed Street, London W2 1NY, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.E. Mercey D.E. Mercey Department of Genitourinary Medicine, The Middlesex Hospital, Mortimer Street, London W1 8AA, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 5, 1 November 1994, Pages 746–747, https://doi.org/10.1111/j.1365-2133.1994.tb05007.x Published: 01 November 1994
Inhaled corticosteroids and survival in chronic obstructive pulmonary disease: does the dose matter?
Authors: D.D. Sin, S.F.P. Man
Journal: European Respiratory Journal (2003)

Recent data suggest that inhaled corticosteroids reduce the number of clinical exacerbations in chronic obstructive pulmonary disease (COPD). It remains unknown whether a dose/response relationship exists. The present study was conducted to evaluate the long-term impact of varying doses of inhaled corticosteroids on COPD mortality. Hospital discharge data were used to identify all patients aged ≥65 yrs recently hospitalised due to COPD in Alberta, Canada (n=6,740). The relative risk (RR) for all-cause mortality was compared across different dose categories of inhaled corticosteroids (none and low, medium and high doses) following hospital discharge. Inhaled corticosteroid therapy after discharge was associated with a 25% relative reduction in risk for all-cause mortality (RR 0.75, 95% confidence interval (CI) 0.68–0.82). Patients on medium- or high-dose therapy showed lower risks for mortality than those on low doses (RR 0.77, 95% CI 0.69–0.86 for low dose; RR 0.48, 95% CI 0.37–0.63 for medium dose; and RR 0.55, 95% CI 0.44–0.69 for high dose). Use of inhaled corticosteroids following hospital discharge for chronic obstructive pulmonary disease was associated with a significant reduction in the overall mortality rate. Low- was inferior to medium- or high-dose therapy in protecting against mortality in chronic obstructive pulmonary disease.
Ets-1 and Ets-2 Transcription Factors Are Essential for Normal Coronary and Myocardial Development in Chicken Embryos
Authors: Heleen Lie-Venema, Adriana C. Gittenberger-de Groot, Louis J.P. van Empel, Marit J. Boot, Henri Kerkdijk, Eric de Kant, Marco C. DeRuiter
Journal: Circulation Research (2003)

In the development of a functional myocardium and formation of the coronary vasculature, epicardium-derived cells play an essential role. The proepicardial organ contributes to the developing coronary system by delivering mural cells to the endothelium-lined vessels. In search of genes that regulate the behavior of (pro)epicardial cells, the Ets-1 and Ets-2 transcription factors stand out as strong candidates. In the present study, the hypothesis that Ets transcription factors have a role in proper coronary and myocardial development was tested via antisense technology, by targeting Ets-1 and Ets-2 mRNAs to downregulate protein expression in chicken embryos. The results suggest that hereby the development of the coronary system is hampered, primarily by defects in the process of epithelial-mesenchymal transformation of the mesothelia of the primary and secondary heart fields. This was indicated by a lack of periarterial and epicardial mesenchyme, of peripheral coronary smooth muscle cells, and changes in myocardial morphology. A defect in myocardial perfusion caused by the absence of one or both coronary ostia seems to be "solved" by the development of numerous small fistulae connecting the ventricular lumen with the subepicardially located coronary vessels. The presence of coronary vascular aberrations in the antisense-Ets phenotype enabled us for the first time to study abnormal coronary development in a model that is not lethal to the embryo.
The best laid schemes of airway repair
Authors: Emma L. Rawlins, Adam Giangreco
Journal: European Respiratory Journal (2014)

Introduction: Reslizumab (RES), a humanized anti-human interleukin-5, is under development for patients with moderate to severe, persistent asthma with elevated eosinophils (EOS).

Objectives: To compare the efficacy and safety of RES vs placebo (PBO) in subjects with asthma and elevated EOS.

Methods: This was a multicenter, PBO-controlled, double-blind, 16-week study ([NCT01270464][1]). Subjects (N=311) were 12-75 years of age with uncontrolled asthma on at least medium ICS, had an asthma control questionnaire (ACQ) score ≥1.5, and blood EOS level of ≥400/µL. Randomization was to intravenous RES 0.3 or 3.0 mg/kg or PBO once every 4 weeks. Efficacy variables included pre-dose, pre-bronchodilator pulmonary function (FEV1, primary variable) and ACQ scores.

Results: Following 16 weeks of therapy, RES (0.3 and 3.0 mg/kg) significantly improved overall FEV1 ( P ≤0.024) and ACQ score ( P ≤0.033) vs PBO (treatment difference vs PBO: 115 and 160 mL, FEV1 and 0.238 and 0.359 ACQ, respectively); improvements for RES 3.0 mg/kg vs PBO were observed in both measures (153 mL, FEV1; -0.283, ACQ) as early as 4 weeks ( P ≤0.015) and maintained over the duration of the study. Clinically meaningful improvements in FVC (130 mL, P =0.017) and FEF25-75% (0.233 L/s; P =0.055) were noted only for the 3.0 mg/kg dose. The most commonly reported AEs in any treatment group were asthma, headache, nasopharyngitis, bronchitis, and upper respiratory tract infection.

Conclusion: In subjects with elevated blood EOS, 4 monthly doses of RES were well tolerated and associated with improvements in pulmonary function and patient-reported asthma control on top of standard-of-care therapies.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01270464&atom=%2Ferj%2F44%2FSuppl_58%2FP299.atom
Inhibition of tumor growth by elimination of granulocytes.
Authors: L A Pekarek, B A Starr, A Y Toledano, H Schreiber
Journal: The Journal of Experimental Medicine (1995)

As observed for many types of cancers, heritable variants of ultraviolet light-induced tumors often grow more aggressively than the parental tumors. The aggressive growth of some variants is due to the loss of a T cell-recognized tumor-specific antigen; however, other variants retain such antigens. We have analyzed an antigen retention variant and found that the variant tumor cells grow at the same rate as the parental tumor cells in vitro, but grew more rapidly than the parental cells in the T cell-deficient host. The growth of the variant cells was stimulated in vitro by factors released from tumor-induced leukocytes and by several defined growth factors. In addition, the variant cancer cells actually attracted more leukocytes in vitro than the parental cells. Furthermore, elimination of granulocytes in vivo in nude mice by a specific antigranulocyte antibody inhibited the growth of the variant cancer, indicating that this tumor requires granulocytes for rapid growth.
Coinheritance of the HR2 Haplotype in the Factor V Gene Confers an Increased Risk of Venous Thromboembolism to Carriers of Factor V R506Q (Factor V Leiden)
Authors: E.M. Faioni, F. Franchi, P. Bucciarelli, M. Margaglione, V. De Stefano, G. Castaman, G. Finazzi, P.M. Mannucci
Journal: Blood (1999)
SARCOMAS IN HAMSTERS AFTER INJECTION WITH ROUS CHICKEN TUMOR MATERIAL
Authors: C. G. Ahlström, Nils Forsby
Journal: The Journal of Experimental Medicine (1962)

Newborn hamsters were injected subcutaneously with a suspension of finely minced Rous chicken sarcoma (Schmidt-Ruppin strain). After an interval of about 2 weeks, progressively growing sarcomas developed at the site of injection in almost all animals. Also in adult hamsters inoculated intramuscularly with the same material sarcomas developed at the site of injection within 2 to 4 months. Secondary growths appeared on the peritoneal surface, in the retroperitoneal and mediastinal lymph nodes and in the lungs. The sarcomas usually had a pleomorphic appearance and showed a certain resemblance to rhabdomyosarcoma, but sometimes they had the character of spindle cell sarcomas of varying degree of maturity. Sarcomas were not only obtained in hamsters injected with cellular material from the Rous chicken sarcoma but were also seen in hamsters which were injected at birth or when 2 months' old with supernatant fluid obtained by repeated centrifugation of suspensions of homogenized chicken sarcoma, and presumed to be cell-free. The hamster sarcoma was transplanted to a newborn hamster and could then without difficulties be passed in series in hamsters. All attempts to transfer the sarcoma from hamster to hamster by means of cell-free material from the hamster sarcoma failed. On the other hand, material from the hamster sarcomas inoculated into chickens induced rapidly growing Rous sarcomas at the site of inoculation. This proved possible not only with material from the first but also from later passages of the tumor in hamsters. It is concluded that the strain of Rous virus used has the capacity to induce sarcomas not only in chickens but also in hamsters.
Nilutamide pneumonitis: a report on eight patients.
Authors: P Pfitzenmeyer, P Foucher, F Piard, B Coudert, M L Braud, P Gabez, S Lacroix, J P Mabille, P Camus
Journal: Thorax (1992)

BACKGROUND: Nilutamide is a new, specific synthetic antiandrogen, released in several countries for the treatment of metastatic carcinoma of the prostate. Eight patients at the University Medical Centre at Dijon and affiliated referring hospitals developed reversible pulmonary opacities and respiratory symptoms while taking the drug. METHODS: Records of eight patients who developed new, otherwise unexplained chest opacities while taking nilutamide were reviewed. In each patient a careful aetiological search was made for other environmental or endogenous causes. Six patients underwent bronchoalveolar lavage, and lavage fluid was cultured. Corticosteroids were not given, unless gas exchange was compromised (two patients). RESULTS: The eight patients (all male) had had carcinoma of the prostate diagnosed on average 10.2 months earlier. All had improved with nilutamide, with a dramatic decrease of prostate specific antigen levels. Seven had received nilutamide at the recommended dosage of 150 mg/day, and one had received twice that amount. Treatment had lasted on average 113 (range 10-225) days, and the mean cumulated exposure was 21.8 (3-38) grams. The chest radiographs showed bilateral infiltrates, with no consistent topographic predilection. A restrictive lung defect was present in six patients and hypoxia in all (mean arterial oxygen tension (PaO2) 6.6 kPa). Bronchoalveolar lavage showed lymphocytosis in four patients and neutrophilia in two. The outcome was favourable in all patients after they had stopped nilutamide only (five patients), with corticosteroids (two patients) or a simple reduction of nilutamide from 300 to 150 mg/day (one patient). Recovery was associated with improvement of pulmonary function and PaO2. CONCLUSION: Nilutamide is associated with interstitial pneumonitis in about 1% of patients and appears reversible.
A two-year sonographic follow-up after intratendinous injection therapy in patients with tennis elbow: Figure 1a–e
Authors: E Zeisig, M Fahlström, L Öhberg, H Alfredson
Journal: British Journal of Sports Medicine (2008)

Background Tennis elbow is a tendinopathy affecting the upper extremity. Recent studies have shown high sensitivity for ultrasound (US) examination and high specificity for colour Doppler (CD) examination. There are no mid- or long-term follow-up investigations of the tendon structure and blood flow using these techniques. Objective To use US and CD to study structure and blood flow in the extensor origin in patients with tennis elbow treated with intratendinous injections. Design Follow-up study Setting Sports Medicine Unit, Umeå University. Patients 25 patients (28 elbows), mean age 46 years (range 27–66), treated with intratendinous injections due to chronic pain from tennis elbow. Method US and CD examination of the extensor origin was carried out at inclusion and at follow-up two years after intratendinous injection treatment with polidocanol and/or a local anaesthetic. Main outcome measurements US (structure) and CD (blood flow) findings. Results All patients had structural tendon changes and high blood flow at inclusion when given the injection treatment. At the two-year follow-up, structural tendon changes were seen in 20/28 elbows and high blood flow was seen in 4/28 elbows. The majority of patients with a good clinical result after treatment had no visible blood flow (17/20), but the structural changes showed no relation to a good result (13/20 remaining changes). Conclusions Doppler findings, but not structure, might be related to the clinical result after intratendinous injection treatment of tennis elbow.
Association of Maternal Obesity Before Conception with Poor Lactation Performance
Authors: Kathleen Maher Rasmussen
Journal: Annual Review of Nutrition (2007)

The objective of this review is to evaluate the evidence for a link between maternal obesity and poor lactation performance. In nonhuman species, excess maternal fatness is deleterious for lactation and also for maternal health and survival. These effects occur during pregnancy and as milk production is beginning. They may result in poor growth and survival of the young. In women, there is a negative association between maternal obesity and the initiation as well as the continuation of breastfeeding. This appears to be derived from biological as well as sociocultural factors that are still poorly understood. Excessive gestational weight gain, complications of pregnancy and delivery, and the condition of the infant at birth may also contribute to this association. Given the increasingly high rates of obesity among women of reproductive age worldwide and the importance of breastfeeding for infant health, further study of this association is essential.
Preconceptions and prerequisites: Understanding the function of synaptic plasticity will also depend on a better systems-level understanding of the multiple types of memory
Authors: Richard G. M. Morris
Journal: Behavioral and Brain Sciences (1997)

Although it is not their fault, Shors &amp; Matzel's attempt to review the LTP and learning hypothesis suffers from there being no clear published statement of the idea. Their summary of relevant evidence is not without error, however, and it oversimplifies fundamental issues relating to NMDA receptor function. Their attentional hypothesis is intriguing but requires a better systems-level understanding of how attention contributes to cognitive function.
Etiology and Prevention of Cervical Adenocarcinomas
Authors: Allan Hildesheim, Amy Berrington de González
Journal: JNCI Journal of the National Cancer Institute (2006)

Adenocarcinomas of the uterine cervix (ACs) constitute a relatively rare histologic form of cervical cancer. However, while rates of the more common squamous cell carcinomas of the cervix (SCC) have shown consistent declines in incidence over time in countries where effective cytological screening programs exist, rates of AC have increased over the same period ( 1 – 3 ) . This has led to an increase in the proportion of cervical cancers attributable to AC in many countries. In the United States, ACs now make up more than 20% of all cervical cancer cases diagnosed each year ( 4 ) . The underlying reasons for the increases observed for AC are not well understood. They are likely due to a complex interplay between temporal changes in exposures that predispose to the development of AC and changes in cervical cancer screening practices ( 1 ) . Changes in screening practices and their likely impact on AC rates are in themselves diffi cult to understand because they include changes that are likely to have countervailing effects on disease rates. For example, increased awareness of AC, improved diagnostic classifi cation of these conditions, and improvements in cervical sampling devices and slide preparation methods might initially result in increased detection of invasive AC. These improvements would also lead to increased detection of AC at an earlier — in situ — state, which would subsequently lead to decreases in overall rates of invasive AC. Unlike the situation with SCC, however, this predicted long-term impact of improved screening on AC rates might be muted by limitations resultant from the diffi culty of detecting AC, which often arise deep in the endocervical canal, in areas that despite the improvements in screening alluded to above are still not easily sampled during routine screening. In this issue of the Journal, Castellsague and colleagues report fi ndings from a multicenter study of AC ( 5 ) . The results have important implications for our understanding of both the causes and possible prevention of AC. Each of these aspects is discussed below.
Myocardial High Energy Phosphate Stores in Acutely Induced Hypoxic Heart Failure
Authors: PETER E. POOL, JAMES W. COVELL, CHARLES A. CHIDSEY, EUGENE BRAUNWALD
Journal: Circulation Research (1966)

In order to determine the relation between depression of myocardial function and the myocardial high energy phosphate stores during acute hypoxia, a technique for serial evaluation of these stores was developed. Acute hypoxia was induced in 18 anesthetized dogs and serial determinations of adenosine triphosphate (ATP) and creatine phosphate (CP) were made while myocardial function was continuously measured. Myocardial concentrations of ATP were maintained even in the presence of severe hypoxia and myocardial failure. There was a small depression of the average myocardial CP concentration during early heart failure. However, in more than one-third of the dogs there was no significant depression of CP concentration at this time. It is concluded that hypoxic depression of myocardial function is not initiated by a decrease in the total myocardial high energy phosphate stores. The possibility could not be excluded that a particular fraction of the high energy phosphate store is decreased when myocardial failure is induced by hypoxia.
Expression of Endothelial Nitric Oxide Synthase in Human Peritoneal Tissue
Authors: MARÍA M. ARRIERO, JUAN A. RODRÍGUEZ-FEO, ÁNGEL CELDRÁN, LOURDES SÁNCHEZ DE MIGUEL, FERNANDO GONZÁLEZ-FERNÁNDEZ, JOSÉ FORTES, ANA REYERO, OCTAVIO FRIEYRO, JUAN C. DE LA PINTA, ANGELES FRANCO, CARLOS PASTOR, SANTOS CASADO, ANTONIO LÓPEZ-FARRÉ
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Changes in the expression of endothelial nitric oxide synthase (eNOS) in the peritoneum could be involved in the peritoneal dysfunction associated with peritoneal inflammation. Demonstrated recently in bovine endothelial cells was the existence of cytosolic proteins that bind to the 3′-untranslated region (3′-UTR) of eNOS mRNA and could be implicated in eNOS mRNA stabilization. The present work demonstrates that eNOS protein is expressed in human endothelial and mesothelial peritoneal cells. Escherichia coli lipopolysaccharide shortened the half-life of eNOS message, reducing eNOS protein expression in peritoneal mesothelial and endothelial cells. Moreover, under basal conditions, human peritoneal samples expressed cytosolic proteins that bind to the 3′-UTR of eNOS mRNA. The cytosolic proteins that directly bind to 3′-UTR were identified as a 60-kD protein. After incubation of human peritoneal samples with lipopolysaccharide, the binding activity of the cytosolic 60-kD protein increased in a time-dependent manner. Studies are now necessary to determine the involvement of this 60-kD protein in the regulation of eNOS expression in peritoneal cells and particularly its involvement in the peritoneal dysfunction associated with inflammatory reactions.