tbuckley/cabot-search huggingface dataset:
Inotropic effects of theophylline on foreshortened canine diaphragm.
Authors: G Gayan-Ramirez, M Decramer
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

We previously demonstrated that theophylline exerted greater inotropic effects on foreshortened canine diaphragm than on diaphragm placed at resting length in vivo (1). To ensure that these effects result from an effect on the muscle itself, they were examined in vitro. Thus, the effects of increasing doses of theophylline (20, 100, 200, and 400 mg/L) or addition of Krebs solution on twitch tension (Pt) of bundles placed at optimal length (Lo) and 70% Lo were compared. At Lo, compared with time-matched control, Pt significantly increased after theophylline (e.g., 37 +/- 32 versus -8 +/- 12% after 400 mg/L) except with 20 mg/L. At 70% Lo, Pt increased with all theophylline concentrations in a dose-related manner (e.g., 14 +/- 15 versus -6 +/- 7% and 114 +/- 57 versus -8 +/- 11% after 20 and 400 mg/L, respectively). Time to peak tension and half-relaxation time remained unchanged after theophylline both at Lo and 70% Lo. In addition, for a given concentration, twitch potentiation was significantly greater at 70% Lo than at Lo, the difference increasing with increasing concentration (e.g., 3 times greater with 400 mg/L). We conclude that theophylline-induced inotropic effects on Pt were more pronounced on foreshortened canine diaphragm bundles than on bundles placed at Lo. These observations confirm that theophylline-induced inotropic effects on foreshortened muscle previously observed in vivo are likely to result from a direct effect on muscle contractility.
C-Reactive Protein Induces Apoptosis in Human Coronary Vascular Smooth Muscle Cells
Authors: Florian Blaschke, Dennis Bruemmer, Fen Yin, Yasunori Takata, Wei Wang, Michael C. Fishbein, Takafumi Okura, Jitsuo Higaki, Kristof Graf, Eckart Fleck, Willa A. Hsueh, Ronald E. Law
Journal: Circulation (2004)

Accumulating evidence suggests that C-reactive protein (CRP), in addition to being a predictor of coronary events, may have direct actions on the vessel wall in the evolution of atherosclerosis. Although accumulation of vascular smooth muscle cells (VSMCs) in the intima is a key event in the development of arterial lesions, apoptosis of VSMCs also plays an important role in progression of atherosclerotic lesions and contributes to increased plaque vulnerability.In the present study we demonstrate that CRP induces caspase-mediated apoptosis of human coronary VSMCs. DNA microarray analysis was used to identify CRP-regulated genes. The growth arrest- and DNA damage-inducible gene 153 (GADD153) mRNA expression was prominently upregulated by CRP. As confirmed by Northern blot analysis, CRP induced a time- and dose-dependent increase of GADD153 mRNA expression. GADD153, a gene involved in growth arrest and apoptosis in vascular and nonvascular cells, is regulated at both transcriptional and posttranscriptional levels. CRP regulation of GADD153 mRNA expression in VSMCs occurs primarily at the posttranscriptional level by mRNA stabilization. Small interfering RNA (siRNA) specifically targeted to GADD153 reduced CRP-induced apoptosis. GADD153 also specifically colocalized to apoptotic VSMCs in human coronary lesions, further supporting a functional role for GADD153 in CRP-induced cell death.These results demonstrate that GADD153 is a CRP-regulated gene in human VSMCs and plays a causal role in CRP-induced apoptosis. Pharmacological targeting of CRP expression or action may provide a novel therapy for atherosclerosis.
Angiotensin receptor blockers and cardiovascular outcomes
Authors: F. D. R. Hobbs
Journal: BMJ (2011)

Robust evidence refutes previous suggestions of an increased risk

In the linked systematic review and meta-analysis (doi:10.1136/bmj.d2234), Bangalore and colleagues assess cardiovascular and other outcomes associated with angiotensin receptor blockers (ARBs). They found firm evidence to refute previous concerns that these drugs increase the risk of myocardial infarction. They also found that compared with controls, ARBs reduce the risk of stroke, heart failure, and new onset diabetes.1 

In balancing risk against benefit health systems commonly raise safety concerns about drugs in common use. Such concerns may stem from the clear demonstration of catastrophic risk, such as was identified for thalidomide, and result in immediate and essential withdrawal of the drug from the market. Withdrawal can also be voluntary, as for drugs that do not pose a specific risk but have no advantages over competitor products. The cyclo-oxygenase-2 selective non-steroidal anti-inflammatory drugs rofecoxib and valdecoxib, which resulted in greater use of non-selective non-steroidal anti-inflammatory drugs plus proton pump inhibitors, provide such an example.2

Some drugs that were rapidly withdrawn on safety grounds would have best been withdrawn gradually or not at all. An example of this is the precipitate 1995 withdrawal of third generation oral combined contraceptives (because of a 1.7 relative risk but …
Acute Respiratory Distress Syndrome Caused by Pulmonary and Extrapulmonary Disease
Authors: LUCIANO GATTINONI, PAOLO PELOSI, PETER M. SUTER, ALESSIA PEDOTO, PAOLA VERCESI, ALFREDO LISSONI
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

To assess the possible differences in respiratory mechanics between the acute respiratory distress syndrome (ARDS) originating from pulmonary disease (ARDSp) and that originating from extrapulmonary disease (ARDSexp) we measured the total respiratory system (Est,rs), chest wall (Est,w) and lung (Est,L) elastance, the intra-abdominal pressure (IAP), and the end-expiratory lung volume (EELV) at 0, 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with ARDSp and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and EELV were similar in both groups of patients. The Est,L, however, was markedly higher in the ARDSp group than in the ARDSexp group (20.2 ± 5.4 versus 13.8 ± 5.0 cm H2O/L, p < 0.05), whereas Est,w was abnormally increased in the ARDSexp group (12.1 ± 3.8 versus 5.2 ± 1.9 cm H2O/L, p < 0.05). The IAP was higher in ARDSexp than in ARDSp (22.2 ± 6.0 versus 8.5 ± 2.9 cm H2O, p < 0.01), and it significantly correlated with Est,w (p < 0.01). Increasing PEEP to 15 cm H2O caused an increase of Est,rs in ARDSp (from 25.4 ± 6.2 to 31.2 ± 11.3 cm H2O/L, p < 0.01) and a decrease in ARDSexp (from 25.9 ± 5.4 to 21.4 ± 55.5 cm H2O/L, p < 0.01). The estimated recruitment at 15 cm H2O PEEP was − 0.031 ± 0.092 versus 0.293 ± 0.241 L in ARDSp and ARDSexp, respectively (p < 0.01). The different respiratory mechanics and response to PEEP observed are consistent with a prevalence of consolidation in ARDSp as opposed to prevalent edema and alveolar collapse in ARDSexp.
A double-blind, vehicle-controlled study evaluating masoprocol cream in the treatment of actinic keratoses on the head and neck
Authors: Elise A. Olsen, M. Lisa Abernethy, Carol Kulp-Shorten, Jeffrey P. Callen, Scott D. Glazer, Arthur Huntley, Michael McCray, Alicia B. Monroe, Eduardo Tschen, John E. Wolf
Journal: Journal of the American Academy of Dermatology (1991)
Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: A one year prospective study
Authors: T. Conrozier, T. Saxne, C. S. S. Fan, P. Mathieu, A.-M. Tron, D. Heinegard, E. Vignon
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To evaluate serum concentations of cartilage oligomeric matrix protein (COMP) and bone sialoprotein (BSP) as predictors of disease progression in hip osteoarthrtitis (OA). <h3>METHODS</h3> Forty eight consecutive patients, referred to hospital for symptomatic hip OA, (ACR criteria) were monitored in a one year prospective trial with radiographs and serum samples. The radiographs were graded for joint space narrowing, osteophytes, and sclerosis and the joint space width was measured by a digitised image analyser. Serum COMP and BSP were quantified by immunoassays. <h3>RESULTS</h3> The COMP concentrations at baseline correlated with the joint space width at entry and with its yearly mean narrowing (<i>r</i> = 0.38, p = 0.002) but not with joint space narrowing grade progression. The concentrations were higher in patients with bilateral hip OA (p = 0.03). The serum BSP concentrations at baseline were unrelated to OA progression but correlated inversely to the osteophyte grade (<i>r</i> = −0.36, p = 0.004) and sclerosis grade (<i> r</i> = −0.42, p = 0.0004). <h3>CONCLUSION</h3> Serum COMP seems to be a surrogate marker of OA and may be of interest for the detection of patients at risk of rapidly progressing disease in hip OA. Serum BSP changes seem to reflect alterations in the subchondral bone turnover in hip OA. Measurement of joint space width using a digitised image analyser is a sensitive way of assessing OA progression that facilitates evaluation of tissue markers in relation to anatomical changes in the joint.
Upper respiratory tract infection is reduced in physically fit and active adults
Authors: David C Nieman, Dru A Henson, Melanie D Austin, Wei Sha
Journal: British Journal of Sports Medicine (2010)

Objective Limited data imply an inverse relationship between physical activity or fitness level and the rates of upper respiratory tract infection (URTI). The purpose of this study was to monitor URTI symptoms and severity in a heterogeneous group of community adults and contrast across tertiles of physical activity and fitness levels while adjusting for potential confounders. Design A group of 1002 adults (ages 18–85 years, 60% female, 40% male) were followed for 12 weeks during the winter and fall seasons while monitoring URTI symptoms and severity using the Wisconsin Upper Respiratory Symptom Survey. Subjects reported frequency of aerobic activity, and rated their physical fitness level using a 10-point Likert scale. A general linear model, with adjustment for seven confounders, was used to examine the effect of exercise frequency and fitness level on the number of days with URTI and severity of symptoms. Results The number of days with URTI during the 12-week period was significantly reduced, 43% in subjects reporting ≥5 days/week aerobic exercise compared to those who were largely sedentary (≤1 day/week) and 46% when comparing subjects in the high versus low fitness tertile. URTI severity and symptomatology were also reduced 32% to 41% between high and low aerobic activity and physical fitness tertiles. Conclusions Perceived physical fitness and frequency of aerobic exercise are important correlates of reduced days with URTI and severity of symptoms during the winter and fall common cold seasons.
Glucose, bronchial secretions and MRSA
Authors: J S Brown
Journal: Thorax (2005)

Association of MRSA infection with abnormal glucose levels in respiratory tract secretions

Strains of Staphylococcus aureus resistant to first line antibiotic therapy (the penicillinase resistant penicillins cloxacillin, flucloxacillin and methicillin), termed methicillin resistant S aureus (MRSA), first appeared in 1961 and are now widespread worldwide.1 In the UK MRSA is particularly prevalent, especially on intensive care wards, causing a variety of important nosocomial infections. Infection with MRSA usually requires parenteral therapy with a glycopeptide antibiotic and frequently substantially prolongs the patient’s hospital admission. Isolation of carriers places considerable stress on available bed resources and local outbreaks can even result in temporary ward closures. As a consequence, the human and financial burden of MRSA is significant, and this is reflected by the adoption of improved control of hospital acquired infections by a major political party as a major election “pledge”.

The paper by Philips et al 2 in this issue of Thorax reports a possible association between a positive culture for MRSA from bronchial aspirates from patients in an intensive care ward and abnormally high levels of glucose in the bronchial aspirates (ranging from 2.7 to 4.4 mmol/l). MRSA infection was just over twice as likely in patients with abnormal glucose levels in bronchial aspirates, but the overall incidence of 45% for isolation of MRSA from the respiratory tract is surprisingly high and may limit the applicability of these results to other hospitals. However, if the association of MRSA with abnormal …
THE LYMPHOCYTE RESPONSE TO PRIMARY MOLONEY SARCOMA VIRUS TUMORS IN BALB/c MICE
Authors: E. W. Lamon, H. Wigzell, E. Klein, B. Andersson, H. M. Skurzak
Journal: The Journal of Experimental Medicine (1973)

Adult BALB/c mice were injected with Moloney sarcoma virus (MSV) after which the animals' lymphocytes were examined for activity against Moloney leukemia virus (MLV) antigen-bearing target cells at 5-day intervals for 30 days. Lymphocytes from these animals and appropriately matched controls were fractionated into B cell-deficient (primarily T cells) and T cell-deficient (primarily B cells) subpopulations. Macrophages were removed using iron powder and magnetism. The unfractionated lymphocytes, T cells, and non-T cells were then tested in microcytotoxicity tests. Antigen-specific activity was found in the unfractionated lymphocytes from animals that had not yet developed palpable tumors and from regressor animals. The T cells were active just before tumor development and just after regression; however, by day 30 after virus infection (8–10 days after regression) the T cell subpopulation was much less active. The non-T cell subpopulation was also active before tumor development and soon after regression. However, this activity continued to rise after regression and was highest at 30 days. At day 15 (peak tumor size) neither subpopulation was active. The activity was demonstrated to be specific for the MLV-determined cell surface antigen by testing on control target cells that were MLV antigen negative and by comparison of the inhibitory effects with lymphocytes immune to a nonpertinent antigen as well as normal lymphocytes. The non-T cells were tested for activity before and after removal of macrophages with iron powder and magnetism. Such cells were significantly more active after removal of the macrophages. These data demonstrate specific T cell and non-T cell activity in microcytotoxicity tests with a tumor-specific system and strongly suggest that the non-T cell activity described herein is a B cell function.
Direct conversion of fibroblasts into neural progenitor-like cells by forced growth into 3D spheres on low attachment surfaces
Authors: Guannan Su, Yannan Zhao, Jianshu Wei, Zhifeng Xiao, Bing Chen, Jin Han, Lei Chen, Jian Guan, Renzhi Wang, Qun Dong, Jianwu Dai
Journal: Biomaterials (2013)
Pretreatment CD4 Cell Slope and Progression to AIDS or Death in HIV-Infected Patients Initiating Antiretroviral Therapy—The CASCADE Collaboration: A Collaboration of 23 Cohort Studies
Authors: Marcel Wolbers, Abdel Babiker, Caroline Sabin, Jim Young, Maria Dorrucci, Geneviève Chêne, Cristina Mussini, Kholoud Porter, Heiner C. Bucher
Journal: PLoS Medicine (2010)

Background CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART. Methods and Findings We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46–81) cells/µl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97–1.04) for each 10 cells/µl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/µl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94–1.03, for each 10 cells/µl per year reduction in CD4 cell decline). Conclusions The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/µl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary
Measurement of Vasoconstrictor Tone in the Extremities in Hypertension
Authors: HENRY J. KOWALSKI, SIBLEY W. HOOBLER, S. DONALD MALTON, RICHARD H. LYONS
Journal: Circulation (1953)

Tetraethylammonium (TEA) given intravenously decreases peripheral vascular resistance. The magnitude of the decrement is related directly to the prevailing level of neurogenic vasomotor tone. TEA was administered to hypertensive and normotensive subjects. The decrements in resistance of the foot did not differ between the two groups. The decrements of the forearm also did not differ. These findings suggest that the prevailing level of neurogenic vasomotor tone in the extremities is not increased in hypertension.
A Novel Human tRNA-Dihydrouridine Synthase Involved in Pulmonary Carcinogenesis
Authors: Tatsuya Kato, Yataro Daigo, Satoshi Hayama, Nobuhisa Ishikawa, Takumi Yamabuki, Tomoo Ito, Masaki Miyamoto, Satoshi Kondo, Yusuke Nakamura
Journal: Cancer Research (2005)

Abstract An increased level of dihydrouridine in tRNAPhe was found in human malignant tissues nearly three decades ago, but its biological significance in carcinogenesis has remained unclear. Through analysis of genome-wide gene-expression profiles among non–small cell lung carcinomas (NSCLC), we identified overexpression of a novel human gene, termed hDUS2, encoding a protein that shared structural features with tRNA-dihydrouridine synthases (DUS). The deduced 493-amino-acid sequence showed 39% homology to the dihydrouridine synthase 2 enzyme (Dus2) of Saccharomycescerevisiae and contained a conserved double-strand RNA-binding motif (DSRM). We found that hDUS2 protein had tRNA-DUS activity and that it physically interacted with EPRS, a glutamyl-prolyl tRNA synthetase, and was likely to enhance translational efficiencies. A small interfering RNA against hDUS2 transfected into NSCLC cells suppressed expression of the gene, reduced the amount of dihydrouridine in tRNA molecules, and suppressed growth. Immunohistochemical analysis showed significant association between higher levels of hDUS2 in tumors and poorer prognosis of lung cancer patients. Our data imply that up-regulation of hDUS2 is a relatively common feature of pulmonary carcinogenesis and that selective suppression of hDUS2 enzyme activity and/or inhibition of formation of the hDUS2-tRNA synthetase complex could be a promising therapeutic strategy for treatment of many lung cancers.
Mortgaging Our Future — The Cost of Medical Education
Authors: Gail Morrison
Journal: New England Journal of Medicine (2005)

The cost of obtaining a medical education has been spiraling upward for the past 20 years. Despite a lot of rhetoric in articles1,2 and at meetings of the Association of American Medical Colleges, nothing has happened to change the alarming pattern. The average tuition and fees at public medical schools during the 2003–2004 academic year amounted to $16,153, and the corresponding figure for private schools was $32,588.3 Adding $20,000 to $25,000 for living expenses, books, and equipment brings the estimated cost of four years of attendance to about $140,000 for public schools and $225,000 for private schools.The continuing . . .
THE CENTRAL EFFECTORS OF CELL DEATH IN THE IMMUNE SYSTEM
Authors: Jeffrey C. Rathmell, Craig B. Thompson
Journal: Annual Review of Immunology (1999)

▪ Abstract The immune system relies on cell death to maintain lymphoid homeostasis and avoid disease. Recent evidence has indicated that the caspase family of cysteine proteases is a central effector in apoptotic cell death and is absolutely responsible for many of the morphological features of apoptosis. Cell death, however, can occur through caspase-independent and caspase-dependent pathways. In the case of cells that are irreversibly neglected or damaged, death occurs even in the absence of caspase activity. In contrast, healthy cells require caspase activation to undergo cell death induced by surface receptors. This review summarizes the current understanding of these two pathways of cell death in the immune system.
Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer
Authors: R.P. Abratt, D. Brune, M.-A. Dimopoulos, J. Kliment, J. Breza, F.P. Selvaggi, P. Beuzeboc, T. Demkow, S. Oudard
Journal: Annals of Oncology (2004)
Home testing kits for HIV apt to get FDA approval
Authors: C. Marwick
Journal: JAMA (1995)

HOME TESTING KITS for spotting the AIDS agent are moving closer to approval. The Food and Drug Administration (FDA) has had a change of heart about approving these kits for detecting the presence of the human immunodeficiency virus (HIV).  The agency's move reverses its earlier position, when it held that these kits could be used only under the supervision of a physician or other qualified health professional. The FDA now says that it would approve the kits for over-the-counter use as long as those with a positive test result are referred for counseling and postmarketing studies are put in place to assess the public health impact.  This decision has once again fired up discussion of the value of home test kits for detecting HIV. Faced with the virtual certainty that the FDA will approve HIV test kits, the group Gays and Lesbians for Individual Liberty held a forum in Washington,
Advances in Supportive Care for Late Effects of Head and Neck Cancer
Authors: Barbara A. Murphy, Jie Deng
Journal: Journal of Clinical Oncology (2015)

As the population of head and neck cancer survivors increases, it has become increasingly important for health care providers to understand and manage late complications of therapy. Functional deficits can be categorized as general health deficits resulting in frailty or debility, head and neck–specific functional deficits such as swallowing and speech, and musculoskeletal impairment as a result of tumor and treatment. Of critical importance is the growing data indicating that swallow therapy and physical therapy may prevent or ameliorate long-term functional deficits. Oral health complications of head and neck therapy may manifest months or years after the completion of treatment. Patients with hyposalivation are at high risk for dental caries and thus require aggressive oral hygiene regimens and routine dental surveillance. Swallowing abnormalities, xerostomia, and poor dentition may result in dietary adaptations that may cause nutritional deficiencies. Identification and management of maladaptive dietary strategies are important for long-term health. Follow-up with primary care physicians for management of comorbidities such as diabetes and hyperlipidemia may help to limit late vascular complications caused by radiation therapy. Herein, we review late effects of head and neck cancer therapy, highlighting recent advances.