tbuckley/cabot-search huggingface dataset:
Granulation Response and Partial Wound Closure Predict Healing in Clinical Trials on Advanced Diabetes Foot Ulcers Treated With Recombinant Human Epidermal Growth Factor
Authors: Carmen M. Valenzuela-Silva, Ángela D. Tuero-Iglesias, Elizeth García-Iglesias, Odalys González-Díaz, Amaurys del Río-Martín, Isis Belkis Yera Alos, José I. Fernández-Montequín, Pedro A. López-Saura
Journal: Diabetes Care (2012)

To determine if partial wound closure surrogate markers proposed for neuropathic, small diabetic foot ulcers (DFUs) can be extended to advanced lesions and if the development of granulation tissue can be used to predict complete healing.Data from two multicenter, double-blind, randomized clinical trials (one of them placebo controlled) that used intralesional recombinant human epidermal growth factor (rhEGF) to promote granulation and healing were used. For confirmation in a larger sample from common clinical practice, the results of an active postmarketing surveillance of rhEGF treatment of DFUs in 60 healthcare units was included. The surrogates evaluated were percent area change, log healing rate, ratio of log areas, and percent of granulation tissue covering the wound area. The tests used were surrogate final end point correlation, receiver operating characteristic curves to discriminate healers from nonhealers, validation tests using logistic regression models, and the proportion-mediated estimation.Two weeks >50% granulation, end of treatment >75% granulation, and 16.1% area change showed significant predictive value (>70% correct classification) for final wound closure. The granulation-based variables fulfilled the criterion that the effect of rhEGF treatment on wound closure was mediated by the surrogate.This work provides the first evidence for the use of granulation tissue development as a predictor of wound healing in advanced DFUs. These results can be useful for clinical trial design, particularly during the exploratory phase of new products.
National Estimates of Insulin-Related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations
Authors: Andrew I. Geller, Nadine Shehab, Maribeth C. Lovegrove, Scott R. Kegler, Kelly N. Weidenbach, Gina J. Ryan, Daniel S. Budnitz
Journal: JAMA Internal Medicine (2014)

IMPORTANCE Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets.OBJECTIVE To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs.DESIGN, SETTING, AND PARTICIPANTS Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011.MAIN OUTCOMES AND MEASURES Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTSBased on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97 648 (95% CI, 64 410-130 887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%)resulted in hospitalization.Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%).Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3)and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years.The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product.CONCLUSIONS AND RELEVANCE Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin.Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts.
Immunologic Control of HIV-1
Authors: Rajesh T. Gandhi, Bruce D. Walker
Journal: Annual Review of Medicine (2002)

▪ Abstract By destroying CD4+ T cells, human immunodeficiency virus-1 (HIV-1) infection results in immunodeficiency and the inability of the immune system to contain the virus in most individuals. Although treatment of HIV-1 infection with potent antiretroviral medications has resulted in enormous clinical benefit, there is a growing recognition of the limitations of this therapy. As a result, novel approaches to treating HIV-1 infection are being considered. One such strategy is immunotherapy, which seeks to boost immune responses against HIV-1 and control the virus. This approach is based on studies of other viruses in which a coordinated immune response contains the chronic infection. Recent studies show that CD4+ helper responses, CD8+ T cell activity, and antibodies may contribute to control of the virus without antiretroviral therapy in some HIV-positive individuals. Based on this understanding of the immunologic correlates of control of HIV-1, exciting new immunotherapeutic strategies for HIV-1 infection are being designed and tested.
UPTAKE AND REDUCTION OF OXIDIZED AND REDUCED ASCORBATE BY HUMAN LEUKOCYTES
Authors: Robert H. Bigley, Libuse Stankova
Journal: The Journal of Experimental Medicine (1974)

Incubation of human leukocytes with dehydroascorbate (DHA) results in an increase in their reduced ascorbate (AA) content and hexose monophosphate shunt (HMS) activity, independent of oxygen supply. Incubation with AA induces these changes only in the presence of oxygen. The increase in HMS activity observed as cell AA increases by 1 µmol is the same during incubation with either DHA or AA. We propose that human leukocytes take up ascorbate as DHA (AA after oxidation to DHA) and reduce it promptly to AA, and that HMS stimulation upon incubation with either AA or DHA is a result of DHA reduction.
Fractionated versus Standard Continuous Light Delivery in Interstitial Photodynamic Therapy of Dunning Prostate Carcinomas
Authors: Zhengwen Xiao, Steve Halls, Dwayne Dickey, John Tulip, Ronald B. Moore
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The study aims to compare the standard/continuous light delivery with fractionated light delivery for interstitial photodynamic therapy (PDT) of prostate cancer. Experimental Design: Dunning R3327 prostate tumor models were established in male syngeneic rats. When tumors reached ∼3,000 mm3, animals were randomized to various treatment groups. Three hours after QLT0074 injection, tumors were illuminated by 690-nm light delivered by a computer-controlled switch, which sequentially directed light to one of the seven optical fibers in cycles. For comparison, tumors were treated with continuous illumination. Tumors treated with light-only served as control. Dynamic contrast-enhanced magnetic resonance imaging was used to monitor tumor perfusion changes before and after PDT. Results: Tumor response (animal survival) to PDT with fractionated light delivery was PDT dose dependent in both tumor models. Rats bearing anaplastic tumor treated by fractionated light (PDT dose: 1.5 mg/kg QLT0074, 900 J light) had a median survival of 51 days with 25% tumor cures compared with that of 26 days with no tumor cure by continuous illumination (P = 0.015) and 14 days by light-only (P = 0.0001). Rats bearing well-differentiated tumor treated by fractionated light had a median survival of 82 days compared with 65 days by continuous illumination (P = 0.001) and 37 days by light-only. PDT with fractionated light generated a perfusion reduction of 80% compared with 52% for continuous illumination in well-differentiated tumors. Conclusions: Fractionated light delivery is more effective than continuous light delivery in PDT of prostate cancer (solid tumors). These results warrant further investigation in clinical trials.
Colistin, rifampicin, and meropenem administered as single agents in a model of pneumonia caused by a carbapenem-resistant Acinetobacter baumannii
Authors: Viviane Cassisa, Marie-Laure Joly-Guillou, Hélène Pailhoriès, Noémie Coron, Matthieu Eveillard
Journal: Journal of Infection (2014)
Relationship between socioeconomic status and asthma: a longitudinal cohort study
Authors: R J Hancox
Journal: Thorax (2004)

There is conflicting information about the relationship between asthma and socioeconomic status, with different studies reporting no, positive, or inverse associations. Most of these studies have been cross sectional in design and have relied on subjective markers of asthma such as symptoms of wheeze. Many have been unable to control adequately for potential confounding factors.We report a prospective cohort study of approximately 1000 individuals born in Dunedin, New Zealand in 1972-3. This sample has been assessed regularly throughout childhood and into adulthood, with detailed information collected on asthma symptoms, lung function, airway responsiveness, and atopy. The prevalence of these in relation to measures of socioeconomic status were analysed with and without controls for potential confounding influences including parental history of asthma, smoking, breast feeding, and birth order using cross sectional time series models.No consistent association was found between childhood or adult socioeconomic status and asthma prevalence, lung function, or airway responsiveness at any age. Having asthma made no difference to educational attainment or socioeconomic status by age 26. There were trends to increased atopy in children from higher socioeconomic status families consistent with previous reports.Socioeconomic status in childhood had no significant impact on the prevalence of asthma in this New Zealand born cohort. Generalisation of these results to other societies should be done with caution, but our results suggest that the previously reported associations may be due to confounding.
Neutrophils Promote Aerogenous Spread of Lung Adenocarcinoma with Bronchioloalveolar Carcinoma Features
Authors: Marie Wislez, Martine Antoine, Nathalie Rabbe, Valérie Gounant, Virginie Poulot, Armelle Lavolé, Jocelyne Fleury-Feith, Jacques Cadranel
Journal: Clinical Cancer Research (2007)

Adenocarcinoma with bronchioloalveolar carcinoma (BAC) features is a subtype of non-small cell lung cancers characterized by an intense inflammatory reaction composed of macrophages and neutrophils and by a distinct natural history with intrapulmonary spread leading to death due to respiratory failure. We hypothesized that neutrophils could promote aerogenous spread of lung adenocarcinoma with BAC features.We examined the effect of neutrophils on A549 cell line detachment in vitro and we quantified desquamation of tumor cells on tumor tissue (n = 25) and on matched bronchioloalveolar lavage (n = 17) in vivo in a series of patients with adenocarcinoma with BAC features.Neutrophils induced A549 detachment mediated by signals through cell-to-cell contact. Detached A549 cells were still viable and able to proliferate in vitro. Neutralization studies identified several membrane-bound molecules involved in detachment (i.e., intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, tumor necrosis factor alpha/tumor necrosis factor alpha receptor inhibitor, interleukin-1alpha /interleukin-1alpha receptor, and neutrophil elastase). In tumor tissue, shedding was detected in all samples, with a median shedding score of 42% (range, 4-95%). Micropapillary clusters were detected in 23 of the 25 tumor tissue samples, with a median micropapillary score of 1.40 (range, 0-2.1), and tumor cells were detected in 7 of 17 lavages. The micropapillary score was associated with a high neutrophil count in bronchioloalveolar lavage (P = 0.051). The shedding cell percentage was a significant factor in shorter survival (P = 0.034, univariate Cox analysis).Tumor shedding is induced by neutrophils. It is a significant factor of shorter survival and may be an important event in adenocarcinoma progression.
White Matter Abnormalities in First-Episode Schizophrenia or Schizoaffective Disorder: A Diffusion Tensor Imaging Study
Authors: Philip R Szeszko, Babak A Ardekani, Manzar Ashtari, Sanjiv Kumra, Delbert G Robinson, Serge Sevy, Handan Gunduz-Bruce, Anil K Malhotra, John M Kane, Robert M Bilder, Kelvin O Lim
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The goal of this study was to investigate brain white matter abnormalities by using diffusion tensor imaging in patients with schizophrenia or schizoaffective disorder close to illness onset. METHOD: Ten patients experiencing a first episode of schizophrenia or schizoaffective disorder and 13 healthy volunteers received diffusion tensor imaging and structural magnetic resonance imaging examinations. Voxel-wise analysis was used to compare fractional anisotropy maps in the white matter of the two groups following intersubject registration to Talairach space. RESULTS: Compared with healthy volunteers, patients demonstrated lower fractional anisotropy in the left internal capsule and left-hemisphere white matter of the middle frontal gyrus and posterior superior temporal gyrus. There were no areas of significantly higher fractional anisotropy in patients compared with healthy volunteers. CONCLUSIONS: These findings suggest that white matter pathology is present early in the course of schizophrenia and may be less pronounced than has been found in previous diffusion tensor imaging studies of patients with chronic illness. Further, these data are consistent with hypotheses regarding frontotemporal dysfunction and the failure of left-hemisphere lateralization in the pathophysiology of schizophrenia.
T-Regulatory Cells Shift from a Protective Anti-Inflammatory to a Cancer-Promoting Proinflammatory Phenotype in Polyposis
Authors: Elias Gounaris, Nichole R. Blatner, Kristen Dennis, Fay Magnusson, Michael F. Gurish, Terry B. Strom, Philipp Beckhove, Fotini Gounari, Khashayarsha Khazaie
Journal: Cancer Research (2009)

Abstract T-regulatory (Treg) cells play a major role in cancer by suppressing protective antitumor immune responses. A series of observations (from a single laboratory) suggest that Treg cells are protective in cancer by virtue of their ability to control cancer-associated inflammation in an interleukin (IL)-10–dependent manner. Here, we report that the ability of Treg cells to produce IL-10 and control inflammation is lost in the course of progressive disease in a mouse model of hereditary colon cancer. Treg cells that expand in adenomatous polyps no longer produce IL-10 and instead switch to production of IL-17. Aberrant Treg cells from polyp-ridden mice promote rather than suppress focal mastocytosis, a critical tumor-promoting inflammatory response. The cells, however, maintain other Treg characteristics, including their inability to produce IL-2 and ability to suppress proliferation of stimulated CD4 T cells. By promoting inflammation and suppressing T-helper functions, these cells act as a double-edged knife propagating tumor growth. [Cancer Res 2009;69(13):5490–7]
microRNA Profiling Identifies Cancer-Specific and Prognostic Signatures in Pediatric Malignancies
Authors: Jun S. Wei, Peter Johansson, Qing-Rong Chen, Young K. Song, Steffen Durinck, Xinyu Wen, Adam T.C. Cheuk, Malcolm A. Smith, Peter Houghton, Christopher Morton, Javed Khan
Journal: Clinical Cancer Research (2009)

microRNAs have been shown to be involved in different human cancers. We therefore have performed expression profiles on a panel of pediatric tumors to identify cancer-specific microRNAs. We also investigated if microRNAs are coregulated with their host gene.We performed parallel microRNAs and mRNA expression profiling on 57 tumor xenografts and cell lines representing 10 different pediatric solid tumors using microarrays. For those microRNAs that map to their host mRNA, we calculated correlations between them.We found that the majority of cancer types clustered together based on their global microRNA expression profiles by unsupervised hierarchical clustering. Fourteen microRNAs were significantly differentially expressed between rhabdomyosarcoma and neuroblastoma, and 8 of them were validated in independent patient tumor samples. Exploration of the expression of microRNAs in relationship with their host genes showed that the expression for 43 of 68 (63%) microRNAs located inside known coding genes was significantly correlated with that of their host genes. Among these 43 microRNAs, 5 of 7 microRNAs in the OncomiR-1 cluster correlated significantly with their host gene MIRHG1 (P < 0.01). In addition, high expression of MIRHG1 was significantly associated with high stage and MYCN amplification in neuroblastoma tumors, and the expression level of MIRHG1 could predict the outcome of neuroblastoma patients independently from the current neuroblastoma risk-stratification in two independent patient cohorts.Pediatric cancers express cancer-specific microRNAs. The high expression of the OncomiR-1 host gene MIRHG1 correlates with poor outcome for patients with neuroblastoma, indicating important oncogenic functions of this microRNA cluster in neuroblastoma biology.
Comparison of polymerase chain reaction and pp65 antigen test for early detection of human cytomegalovirus in blood leukocytes of cardiac transplant recipients
Authors: Valeria Ghisetti, Anna Barbui, Enrico Donegani, Marco Bobbio, Philippe Caimmi, Stefano Pansini, Giuseppe Zattera, Angela Pucci, Michele di Summa, Giovanna Marchiaro
Journal: Clinical Microbiology and Infection (1996)
Glucocorticoid-Induced Granulocytosis
Authors: Motohito Nakagawa, Takeshi Terashima, Yulia D’yachkova, Gregory P. Bondy, James C. Hogg, Stephan F. van Eeden
Journal: Circulation (1998)

Background —Glucocorticoid-induced granulocytosis has been attributed to enhanced release of polymorphonuclear leukocytes (PMNs) from bone marrow, delayed apoptosis, and reduced egress of PMNs into tissues. This study was designed to determine the relative contributions of PMNs released from the bone marrow and those entering the circulation from the marginated pool to the granulocytosis produced by a single dose of dexamethasone (2.0 mg/kg) in rabbits. Methods and Results —PMN transit through the mitotic and postmitotic pools of the bone marrow and rate of release of PMNs into the circulation were measured by use of the thymidine analogue 5′-bromo-2′-deoxyuridine (BrdU) to pulse-label PMNs in the bone marrow. The shift of PMNs from the marginated to the circulating pool was measured with BrdU-labeled PMNs transferred from donor rabbits to recipients before dexamethasone was delivered. The data show that dexamethasone increased bone marrow release of PMNs and shortened their transit time through the postmitotic pool ( P &lt;0.001) but not the mitotic pool of the bone marrow ( P &gt;0.05). Dexamethasone slowed the clearance of BrdU-labeled PMNs from the circulation ( P &lt;0.05) and lengthened their disappearance (half-life) from the circulation compared with control (half-life, 4.95 versus 9.45 hours). At 6 hours after dexamethasone, bone marrow release contributed ≈10%, mobilization from the marginated pool ≈61%, and a lengthened half-life in the circulation ≈29% to the glucocorticoid-induced granulocytosis. Conclusions —We conclude that a single dose of dexamethasone causes a granulocytosis primarily by a shift of PMNs from the marginated to the circulating pool, with a minor contribution from marrow release.
Cardiology: The Evolution of the Science and the Art
Authors: J. Willis Hurst
Journal: JAMA (1993)

Richard Bing and his friends have written a superb book about the evolution of our knowledge of the heart and circulation. He and his coauthors are highly qualified to do so, because they have either been responsible for, or have been observers of, the evolution. Bing quotes Emerson: "As I am so I see; use whatever language we will, we can never say anything but what we are." Bing sets his own stage by adding, "Therefore, for a historian, the personality of the artist or scientist must be an essential element of study." He then traces the scientific ideas that make up the core of the evolution of our knowledge in cardiovascular medicine. Along the way he makes the story interesting by displaying the personality of those who made it happen. The 306-page text deals with the pioneers who were responsible for, or deeply interested in, cardiac catheterization, echocardiography, cardiopulmonary
THE CUTANEOUS TUBERCULIN TEST: Applied to a Series of Definitely Diagnosed Cases of Tuberculosis
Authors: S. L. Cummins
Journal: BMJ (1924)

THE CUTANEOUS TUBERCULIN TEST.I TME DIJURN pass up because of the ileo-caecal valve, and not only will this cause pain and discomfort, but there is also consider- able danger of the caecum bursting or perforating.This operation of shlort-circuiting an irremovable growth is well w-orth doing, for not only is malignant disease of the large bowel of slow growth, but when it is relieved from thle irritation of faecal matter passing over it it will grow eveni more slowly.The way in which the growtll destroys life eaily is, of course, by causing obstruction, and once this dlaniger is removed by the short-circuit many patients live comfortably for a considerable time, often two or three years; a colostomy, of course, achieves the same object, buit it does so often with considerable permanenlt discomfort anid distress to the patient.Rcniovable Growth N?ot Producing 'Obstruction.We now come to our fourth and final class of case, in w-hiichl there is nlo obstruction and the growth proves to be removable, and here our aim and object should be to excise the growth and reunite the ends of the bowel by some form of anastomosis straight away at one sitting.Even in this case, where the growth is removable, there are certain eminent authorities who prefer to make 11o attempt at all to remove the growtlh, but merely do the short-circuiting operation, described above, in all cases, for
A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration
Authors: Clive S. McKimmie, Mark Moore, Alasdair R. Fraser, Thomas Jamieson, Damo Xu, Claire Burt, Nick I. Pitman, Robert J. Nibbs, Iain B. McInnes, Foo Y. Liew, Gerard J. Graham
Journal: Blood (2009)
Should use of 4 hours continuous positive airway pressure per night be considered acceptable compliance?
Authors: Juan F. Masa, Jaime Corral-Peñafiel
Journal: European Respiratory Journal (2014)

Continuous positive airway pressure (CPAP) reduces blood pressure in obstructive sleep apnoea (OSA) patients, as well as in patients with resistant hypertension. The effect of CPAP is directly related to treatment compliance [1–3]. Observational studies have shown a reduction in cardiovascular mortality risk in severe OSA patients treated with CPAP and adequate compliance [4–6]. A recent randomised controlled trial (RCT) showed a reduction in cardiovascular events (including hypertension incidence) in patients with adequate CPAP compliance [7]. However, what is an adequate definition of CPAP compliance?

Ideally, CPAP compliance should take place for as long as the patient is sleeping but, in practice, this occurs in a minority of subjects. Based on several studies, compliance of ≥4 h per night has been considered acceptable. However, dose–response studies have found that different compliance levels achieve different dimensions of clinical improvement [8–11]. For instance, in order …