tbuckley/cabot-search huggingface dataset:
Improving Prostate-Specific Antigen Screening
Authors: Seth A. Strope, Gerald L. Andriole
Journal: Journal of Clinical Oncology (2010)

in the ERSPC, Vickers and colleagues 3 validated the use of a fourkallikrein panel as an adjunct to standard PSA testing. They argue that by improving the performance characteristics of PSA testing, the overall benefits ofscreening with PSA testing could improve. We consider the impact of this panel on three problems known to be associated with PSA-based screening: false positives leading to relatively high biopsy rates and many negative biopsies, overdetection, and overtreatment. Screening for prostate cancer is an individual decision in the United States. The PSA test is used to determine which men are at sufficient risk for prostate cancer to warrant a biopsy. Most men wouldliketoavoidhavingaprostatebiopsyunlessitistrulynecessary, since it is invasive, uncomfortable, and can occasionally have complications including bleeding and sepsis. The kallikrein panel described by Vickers and colleagues appears to help many men avoid prostate biopsies:prostatebiopsiesweredecreasedbyapproximatelyhalfcom
Hemodynamic Spectrum of Vasopressor and Vasodilator Drugs
Authors: Calton M. Lewis
Journal: JAMA (1969)

Hemodynamic effects of vasopressor agents and vasodilator drugs were compared in order to clarify differences which would be of practical significance for their use in treatment of circulatory shock. The alpha-adrenergic agents, methoxamine and phenylephrine hydrochloride, increased arterial pressure and decreased heart rate and venous return. The beta-adrenergic agents, mephentermine and isoproterenol hydrochloride, and the alphaadrenergic blocking agents, phentolamine mesylate and phenoxybenzamine hydrochloride, produced similar hemodynamic effects. Both groups of drugs increased heart rate and venous return. An intermediate response was observed with epinephrine, levarterenol bitartrate, and metaraminol bitartrate, drugs which have<i>both</i>alphaand beta-adrenergic actions. In these studies, the limited significance of a classification which is based on the pressor response became apparent. When the effects are viewed as a spectrum of hemodynamic actions, the apparent paradox between vasopressor and vasodilator therapy for shock is largely resolved.
Should hyperbaric oxygen be used to treat the pregnant patient for acute carbon monoxide poisoning? A case report and literature review
Authors: K B Van Hoesen, E M Camporesi, R E Moon, M L Hage, C A Piantadosi
Journal: JAMA (1989)

Carbon monoxide (CO) is the leading cause of death due to poisoning. Although uncommon, CO poisoning does occur during pregnancy and can result in fetal mortality and neurological malformations in fetuses who survive to term. Uncertainty arises regarding the use of hyperbaric oxygen (HBO) as a treatment for the pregnant patient because of possible adverse effects on the fetus that could be induced by oxygen at high partial pressures. While the dangers of hyperoxia to the fetus have been demonstrated in animal models, careful review of animal studies and human clinical experience indicates that the short duration of hyperoxic exposure attained during HBO therapy for CO poisoning can be tolerated by the fetus in all stages of pregnancy and reduces the risk of death or deformity to the mother and fetus. A case is presented of acute CO poisoning during pregnancy that was successfully treated with HBO. Recommendations are suggested for the use of HBO during pregnancy. (<i>JAMA</i>1989;261:1039-1043)
Thromboregulatory manifestations in human CD39 transgenic mice and the implications for thrombotic disease and transplantation
Authors: Karen M. Dwyer, Simon C. Robson, Harshal H. Nandurkar, Duncan J. Campbell, Hilton Gock, Lisa J. Murray-Segal, Nella Fisicaro, Tharun B. Mysore, Elzbieta Kaczmarek, Peter J. Cowan, Anthony J.F. d’Apice
Journal: Journal of Clinical Investigation (2004)

Extracellular nucleotides play an important role in thrombosis and inflammation, triggering a range of effects such as platelet activation and recruitment, endothelial cell activation, and vasoconstriction. CD39, the major vascular nucleoside triphosphate diphosphohydrolase (NTPDase), converts ATP and ADP to AMP, which is further degraded to the antithrombotic and anti-inflammatory mediator adenosine. Deletion of CD39 renders mice exquisitely sensitive to vascular injury, and CD39-null cardiac xenografts show reduced survival. Conversely, upregulation of CD39 by somatic gene transfer or administration of soluble NTPDases has major benefits in models of transplantation and inflammation. In this study we examined the consequences of transgenic expression of human CD39 (hCD39) in mice. Importantly, these mice displayed no overt spontaneous bleeding tendency under normal circumstances. The hCD39 transgenic mice did, however, exhibit impaired platelet aggregation, prolonged bleeding times, and resistance to systemic thromboembolism. Donor hearts transgenic for hCD39 were substantially protected from thrombosis and survived longer in a mouse cardiac transplant model of vascular rejection. These thromboregulatory manifestations in hCD39 transgenic mice suggest important therapeutic potential in clinical vascular disease and in the control of serious thrombotic events that compromise the survival of porcine xenografts in primates.
Dual blocking of mTor and PI3K elicits a prodifferentiation effect on glioblastoma stem-like cells
Authors: Jun Sunayama, Atsushi Sato, Ken-ichiro Matsuda, Ken Tachibana, Kaori Suzuki, Yoshitaka Narita, Soichiro Shibui, Kaori Sakurada, Takamasa Kayama, Arata Tomiyama, Chifumi Kitanaka
Journal: Neuro-Oncology (2010)

Glioblastoma, the most intractable cerebral tumor, is highly lethal. Recent studies suggest that cancer stem-like cells (CSLCs) have the capacity to repopulate tumors and mediate radio- and chemoresistance, implying that future therapies may need to turn from the elimination of rapidly dividing, but differentiated, tumor cells to specifically targeting the minority of tumor cells that repopulate the tumor. However, the mechanism by which glioblastoma CSLCs maintain their immature stem-like state or, alternatively, become committed to differentiation is poorly understood. Here, we show that the inactivation of mammalian target of rapamycin (mTor) by the mTor inhibitor rapamycin or knockdown of mTor reduced sphere formation and the expression of neural stem cell (NSC)/progenitor markers in CSLCs of the A172 glioblastoma cell line. Interestingly, combination treatment with rapamycin and LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, not only reduced the expression of NSC/progenitor markers more efficiently than single-agent treatment, but also increased the expression of βIII-tubulin, a neuronal differentiation marker. Consistent with these results, a dual PI3K/mTor inhibitor, NVP-BEZ235, elicited a prodifferentiation effect on A172 CSLCs. Moreover, A172 CSLCs, which were induced to undergo differentiation by pretreatment with NVP-BEZ235, exhibited a significant decrease in their tumorigenicity when transplanted either subcutaneously or intracranially. Importantly, similar results were obtained when patient-derived glioblastoma CSLCs were used. These findings suggest that the PI3K/mTor signaling pathway is critical for the maintenance of glioblastoma CSLC properties, and targeting both mTor and PI3K of CSLCs may be an effective therapeutic strategy in glioblastoma.
Effects of psychosocial and individual psychological factors on the onset of musculoskeletal pain: common and site-specific effects
Authors: E S Nahit
Journal: Annals of the Rheumatic Diseases (2003)

Objective: To determine whether adverse psychosocial and individual psychological factors increase the risk of pain across regional sites. Methods: A prospective study was conducted of newly employed workers from 12 diverse occupational groups. Near to the beginning of subjects' employment, details of work related psychosocial factors and individual psychological distress were obtained by means of a self completed questionnaire. Questionnaire follow up after 12 months provided data on these same exposures and ascertained pain at any of four anatomical sites: the low back, shoulder, wrist/forearm, and knee. Results: Of the original 1081 subjects, 829 (77%) provided full details at the one year follow up. Psychosocial work demands and high levels of individual psychological distress were found to have a common effect across sites. Psychological distress was associated with a doubling of the risk of reported pain (odds ratio = 2.1, 95% confidence interval 1.6 to 2.7), while aspects of job demand, poor support from colleagues, and work dissatisfaction were all associated with increased odds of reported pain onset of between 1.4 and 1.7. These effects were almost all common across the four regional pain sites. Conclusions: In cohorts of newly employed workers, certain work related psychosocial factors and individual psychological distress are associated with the subsequent reporting of musculoskeletal pain, and generally this effect is common across anatomical sites.
Dexamethasone as adjunctive therapy in bacterial meningitis. A meta-analysis of randomized clinical trials since 1988
Authors: P B McIntyre, C S Berkey, S M King, U B Schaad, T Kilpi, G Y Kanra, C M Perez
Journal: JAMA (1997)

To evaluate the effectiveness of dexamethasone in bacterial meningitis in the subcategories of causative organism and timing and nature of antibiotic therapy.MEDLINE, HEALTHLINE, and AIDSLINE were searched with the Medical Subject Headings "dexamethasone" and "meningitis" in any language. Bibliographies, conference abstracts, and the authors of identified studies were consulted.Randomized, concurrently controlled trials of dexamethasone therapy in childhood bacterial meningitis published from 1988 to November 1996 were selected. Of 16 studies identified, 5 were not eligible.Data were extracted by means of standard outcomes in a protocol sent to all principal authors.Random-effects meta-analysis models were used to obtain summary estimates. As the incidence of severe hearing loss differed significantly by organism among control subjects, organism-specific estimates were used. In Haemophilus influenzae type b meningitis, dexamethasone reduced severe hearing loss overall (combined odds ratio [OR], 0.31; 95% confidence interval [CI], 0.14-0.69). Similar ORs were obtained after studies were stratified by the timing of administration of dexamethasone (before or with antibiotics vs later) or by type of antibiotic (cefuroxime vs other). In pneumococcal meningitis, only studies in which dexamethasone was given early suggested protection, which was significant for severe hearing loss (combined OR, 0.09; 95% CI, 0.0-0.71) and approached significance for any neurological or hearing deficit (combined OR, 0.23; 95% CI, 0.04-1.05). For all organisms combined, the pooled OR suggested protection against neurological deficits other than hearing loss but was not significant (OR, 0.59; 95% CI, 0.34-1.02). Outcomes were similar in studies that used 2 vs more than 2 days of dexamethasone therapy. Adverse effects were not significantly increased with dexamethasone except for secondary fever. The incidence of gastrointestinal tract bleeding increased with longer duration of dexamethasone treatment (0.5% in controls, 0.8% with 2 days of treatment, 3.0% with 4 days of treatment).The available evidence on adjunctive dexamethasone therapy confirms benefit for H influenzae type b meningitis and, if commenced with or before parenteral antibiotics, suggests benefit for pneumococcal meningitis in childhood. Limiting dexamethasone therapy to 2 days may be optimal.
Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer
Authors: H. Charles Manning, Nipun B. Merchant, A. Coe Foutch, John M. Virostko, Shelby K. Wyatt, Chirayu Shah, Eliot T. McKinley, Jingping Xie, Nathan J. Mutic, M. Kay Washington, Bonnie LaFleur, Mohammed Noor Tantawy, Todd E. Peterson, M. Sib Ansari, Ronald M. Baldwin, Mace L. Rothenberg, Darryl J. Bornhop, John C. Gore, Robert J. Coffey
Journal: Clinical Cancer Research (2008)

To evaluate noninvasive molecular imaging methods as correlative biomarkers of therapeutic efficacy of cetuximab in human colorectal cancer cell line xenografts grown in athymic nude mice. The correlation between molecular imaging and immunohistochemical analysis to quantify epidermal growth factor (EGF) binding, apoptosis, and proliferation was evaluated in treated and untreated tumor-bearing cohorts.Optical imaging probes targeting EGF receptor (EGFR) expression (NIR800-EGF) and apoptosis (NIR700-Annexin V) were synthesized and evaluated in vitro and in vivo. Proliferation was assessed by 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) positron emission tomography. Assessment of inhibition of EGFR signaling by cetuximab was accomplished by concomitant imaging of NIR800-EGF, NIR700-Annexin V, and [18F]FLT in cetuximab-sensitive (DiFi) and insensitive (HCT-116) human colorectal cancer cell line xenografts. Imaging results were validated by measurement of tumor size and immunohistochemical analysis of total and phosphorylated EGFR, caspase-3, and Ki-67 immediately following in vivo imaging.NIR800-EGF accumulation in tumors reflected relative EGFR expression and EGFR occupancy by cetuximab. NIR700-Annexin V accumulation correlated with cetuximab-induced apoptosis as assessed by immunohistochemical staining of caspase-3. No significant difference in tumor proliferation was noted between treated and untreated animals by [18F]FLT positron emission tomography or Ki-67 immunohistochemistry.Molecular imaging can accurately assess EGF binding, proliferation, and apoptosis in human colorectal cancer xenografts. These imaging approaches may prove useful for serial, noninvasive monitoring of the biological effects of EGFR inhibition in preclinical studies. It is anticipated that these assays can be adapted for clinical use.
Computer-Based Health Promotion: Combining Technological Advances with Problem-Solving Techniques to Effect Successful Health Behavior Changes
Authors: D H Gustafson, K Bosworth, B Chewning, R P Hawkins
Journal: Annual Review of Public Health (1987)

In recent decades, public health policy and practice have been increasingly challenged by globalization, even as global financing for health has increased dramatically. This article discusses globalization and its health challenges from a vantage of ...Read More
Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomised controlled superiority trial
Authors: Klaus Rasmussen, Michael Maeng, Anne Kaltoft, Per Thayssen, Henning Kelbæk, Hans Henrik Tilsted, Ulrik Abildgaard, Evald Høj Christiansen, Thomas Engstrøm, Lars Romer Krusell, Jan Ravkilde, Peter Riis Hansen, Knud Nørregaard Hansen, Steen Zabell Abildstrøm, Jens Aarøe, Jan Skov Jensen, Steen Dalby Kristensen, Hans Erik Bøtker, Morten Madsen, Søren Paaske Johnsen, Lisette Okkels Jensen, Henrik Toft Sørensen, Leif Thuesen, Jens Flensted Lassen
Journal: The Lancet (2010)
Genetics of Recurrent Early-Onset Major Depression (GenRED): Final Genome Scan Report
Authors: Peter Holmans, Myrna M. Weissman, George S. Zubenko, William A. Scheftner, Raymond R. Crowe, J. Raymond DePaulo, James A. Knowles, Wendy N. Zubenko, Kathleen Murphy-Eberenz, Diana H. Marta, Sandra Boutelle, Melvin G. McInnis, Philip Adams, Madeline Gladis, Jo Steele, Erin B. Miller, James B. Potash, Dean F. MacKinnon, Douglas F. Levinson
Journal: American Journal of Psychiatry (2007)

Objective: The authors carried out a genomewide linkage scan to identify chromosomal regions likely to contain genes that contribute to susceptibility to recurrent early-onset major depressive disorder, the form of the disorder with the greatest reported risk to relatives of index cases. Method: Microsatellite DNA markers were studied in 656 families with two or more such cases (onset before age 31 in probands and age 41 in other relatives), including 1,494 informative "all possible" affected relative pairs (there were 894 independent affected sibling pairs). Analyses included a primary multipoint allele-sharing analysis (with ALLEGRO) and a secondary logistic regression analysis taking the sex of each relative pair into account (male-male, male-female, female-female). Results: Genomewide suggestive evidence for linkage was observed on chromosome 15q25-q26 (at 105.4 centimorgans [cM]). The authors previously reported genomewide significant linkage in this region in the first 297 families. In the secondary analysis, after empirical genomewide correction for multiple testing, suggestive linkage results were observed on chromosome 17p12 (28.0 cM, excess sharing in male-male and male-female pairs) and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs). Conclusions: These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major depression and related disorders. Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.
Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial
Authors: M. Untch, R.D. Gelber, C. Jackisch, M. Procter, J. Baselga, R. Bell, D. Cameron, M. Bari, I. Smith, B. Leyland-Jones, E. de Azambuja, P. Wermuth, R. Khasanov, F. Feng-yi, C. Constantin, J.I. Mayordomo, C.-H. Su, S.-Y. Yu, A. Lluch, E. Senkus-Konefka, C. Price, F. Haslbauer, T. Suarez Sahui, V. Srimuninnimit, M. Colleoni, A.S. Coates, M.J. Piccart-Gebhart, A. Goldhirsch
Journal: Annals of Oncology (2008)
Insulin Resistance and Cardiovascular Disease Risk Factors in Children of Parents With the Insulin Resistance (Metabolic) Syndrome
Authors: James S. Pankow, David R. Jacobs, Julia Steinberger, Antoinette Moran, Alan R. Sinaiko
Journal: Diabetes Care (2004)

To evaluate whether children of parents with the insulin resistance syndrome (IRS) themselves have greater insulin resistance and unfavorable patterns of cardiovascular disease (CVD) risk factors.This cross-sectional study included 220 white and 36 black children aged 11-15 years identified through a school-based blood pressure screening program, along with 378 of their parents. Measures of insulin resistance (glucose disposal per minute per kilogram of lean body mass in a euglycemic-hyperinsulinemic clamp [Mlbm] and fasting insulin), adiposity, and other CVD risk factors were compared in children with and without a parental history of IRS, defined according to the National Cholesterol Education Program Adult Treatment Panel III consensus definition.Compared with children in whom neither parent had IRS, children who had at least one parent with the syndrome had statistically significantly lower mean Mlbm (12.1 vs. 13.6 mg.kg(-1).min(-1); P=0.04) and higher fasting insulin (geometric means 99 vs. 76 pmol/l; P=0.01) after adjustment for sex, race, age, and Tanner stage. Mean BMI, waist circumference, waist-to-hip ratio, triceps and subscapular skinfolds, and percentage of body fat were also significantly higher in children of an affected parent, but there were no significant differences in lipid or blood pressure levels between the two groups.Insulin resistance and obesity may be the earliest manifestations of IRS in children with a parental history of the syndrome.
Innate Immune Recognition in Infectious and Noninfectious Diseases of the Lung
Authors: Bastian Opitz, Vincent van Laak, Julia Eitel, Norbert Suttorp
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Diseases of the respiratory tract are among the leading causes of death in the world population. Increasing evidence points to a key role of the innate immune system with its pattern recognition receptors (PRRs) in both infectious and noninfectious lung diseases, which include pneumonia, chronic obstructive pulmonary disease, acute lung injury, pneumoconioses, and asthma. PRRs are capable of sensing different microbes as well as endogenous molecules that are released after cell damage. This PRR engagement is the prerequisite for the initiation of immune responses to infections and tissue injuries which can be beneficial or detrimental to the host. PRRs include the Toll-like receptors, NOD-like receptors, RIG-I-like receptors, and cytosolic DNA sensors. The PRRs and their signaling pathways represent promising targets for prophylactic and therapeutic interventions in various lung diseases.
Affective Disorders and Suicide Risk: A Reexamination
Authors: J M Bostwick, V S Pankratz
Journal: American Journal of Psychiatry (2000)

In 1970, Guze and Robins published a meta-analysis of suicide in patients with affective illness that inferred a lifetime risk of 15%. Since then, this figure has been generalized to all depressive disorders and cited uncritically in many papers and textbooks. The authors argue for an alternative estimate of suicide risk and question the generalizability of the Guze and Robins estimate.The authors sorted studies obtained through a literature search that included data pertaining to suicide occurrence in affective illness into one of three groups: outpatients, inpatients, or suicidal inpatients. Suicide risks were calculated meta-analytically for these three groups, as well as for two previously published collections.There was a hierarchy in suicide risk among patients with affective disorders. The estimate of the lifetime prevalence of suicide in those ever hospitalized for suicidality was 8.6%. For affective disorder patients hospitalized without specification of suicidality, the lifetime risk of suicide was 4.0%. The lifetime suicide prevalence for mixed inpatient/outpatient populations was 2.2%, and for the nonaffectively ill population, it was less than 0.5%.The percentage of subjects dead due to suicide (case fatality prevalence) is a more appropriate estimate of suicide risk than the percentage of the dead who died by suicide (proportionate mortality prevalence). More important, it is well established that patients with affective disorders suffer a higher risk of suicide relative to the general population. However, no risk factor, including classification of diagnostic subtype, has been reliably shown to predict suicide. This article demonstrates a hierarchy of risk based on the intensity of the treatment setting. Given that patients with a hospitalization history, particularly when suicidal, have a much elevated suicide prevalence over both psychiatric outpatients and nonpatients, the clinical decision to hospitalize in and of itself appears to be a useful indicator of increased suicide risk.
Carcinogenicity of tobacco and tobacco smoke.
Authors: P R Peacock
Journal: BMJ (1967)

he reached 999 years, and that among others the local clergyman might claim the fees he would normally receive for the burial service.Pockrich was a most remarkable rather offbeat character who produced visionary schemes which caused him to be referred to at a recent meeting of the Section of History in the Royal Irish Academy of Medicine in Ireland as a poor man's Leonardo da Vinci.-