tbuckley/cabot-search huggingface dataset:
Calcium plus Vitamin D Supplementation and the Risk of Colorectal Cancer
Authors: Jean Wactawski-Wende, Jane Morley Kotchen, Garnet L. Anderson, Annlouise R. Assaf, Robert L. Brunner, Mary Jo O'Sullivan, Karen L. Margolis, Judith K. Ockene, Lawrence Phillips, Linda Pottern, Ross L. Prentice, John Robbins, Thomas E. Rohan, Gloria E. Sarto, Santosh Sharma, Marcia L. Stefanick, Linda Van Horn, Robert B. Wallace, Evelyn Whitlock, Tamsen Bassford, Shirley A.A. Beresford, Henry R. Black, Denise E. Bonds, Robert G. Brzyski, Bette Caan, Rowan T. Chlebowski, Barbara Cochrane, Cedric Garland, Margery Gass, Jennifer Hays, Gerardo Heiss, Susan L. Hendrix, Barbara V. Howard, Judith Hsia, F. Allan Hubbell, Rebecca D. Jackson, Karen C. Johnson, Howard Judd, Charles L. Kooperberg, Lewis H. Kuller, Andrea Z. LaCroix, Dorothy S. Lane, Robert D. Langer, Norman L. Lasser, Cora E. Lewis, Marian C. Limacher, JoAnn E. Manson
Journal: New England Journal of Medicine (2006)

Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking.We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study.The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics.Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).
Protection by alpha 1-acid glycoprotein against tumor necrosis factor-induced lethality.
Authors: C Libert, P Brouckaert, W Fiers
Journal: The Journal of Experimental Medicine (1994)

We here report that alpha 1-acid glycoprotein, a typical acute phase protein, protects mice from lethal shock induced by tumor necrosis factor (TNF) or endotoxin. The protection is observed both in normal and in galactosamine-sensitized mice. Optimal desensitization requires at least 3 mg alpha 1-acid glycoprotein administered 2 h before the lethal challenge. Under these conditions, complete inhibition of all TNF-induced metabolic changes was observed: fall in body temperature, release of liver transaminases, enhanced clotting time, and mortality. The known platelet aggregation-inhibitory activity of alpha 1-acid glycoprotein provides a possible explanation for this protective capacity.
Evolution of the Genetic Machinery of the Visual Cycle: A Novelty of the Vertebrate Eye?
Authors: R. Albalat
Journal: Molecular Biology and Evolution (2011)

The discovery in invertebrates of ciliary photoreceptor cells and ciliary (c)-opsins established that at least two of the three elements that characterize the vertebrate photoreceptor system were already present before vertebrate evolution. However, the origin of the third element, a series of biochemical reactions known as the "retinoid cycle," remained uncertain. To understand the evolution of the retinoid cycle, I have searched for the genetic machinery of the cycle in invertebrate genomes, with special emphasis on the cephalochordate amphioxus. Amphioxus is closely related to vertebrates, has a fairly prototypical genome, and possesses ciliary photoreceptor cells and c-opsins. Phylogenetic and structural analyses of the amphioxus sequences related with the vertebrate machinery do not support a function of amphioxus proteins in chromophore regeneration but suggest that the genetic machinery of the retinoid cycle arose in vertebrates due to duplications of ancestral nonvisual genes. These results favor the hypothesis that the retinoid cycle machinery was a functional innovation of the primitive vertebrate eye.
C-Peptide Does Not Affect Ocular Blood Flow in Patients With Type 1 Diabetes
Authors: Elzbieta Polska, Julia Kolodjaschna, Fatmire Berisha, Maria M. Malec, Christian Simader, Michaela Bayerle-Eder, Michael Roden, Leopold Schmetterer
Journal: Diabetes Care (2006)

The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions.The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol . kg(-1) . min(-1) bolus followed by 5 pmol . kg(-1) . min(-1) continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging.Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter.The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was <25%.
Helicobacter pylori infection and dental care.
Authors: P G Hardo, A Tugnait, F Hassan, D A Lynch, A P West, N P Mapstone, P Quirke, D M Chalmers, M J Kowolik, A T Axon
Journal: Gut (1995)

Sixty two patients (mean age 45.6 years) were assessed for oral hygiene and periodontal disease by dental examination before endoscopy. Information about oral care, smoking, and dentures was obtained and samples of dental plaque collected. The presence of Helicobacter pylori in plaque as sought by culture and polymerase chain reaction (PCR), and gastric antral biopsy specimens were taken for histological examination. Although H pylori was detected in the antral specimens of 34 patients (54%) all of the cultures of dental plaque were negative, and PCR was only positive from the dentures of one patient. Smokers had poor oral hygiene, visited their dentist less often, and brushed their teeth less frequently. There was no correlation of H pylori gastritis with either dental hygiene or periodontal disease. These results suggest that dental plaque or dentures are not an important reservoir for H pylori and are probably not a significant factor in transmission of the organism. The conflicting results in published works may be caused by differences in sample collection, culture techniques, or oral contamination from gastric juice as a result of gastro-oesophageal reflux at the time of endoscopy.
Persistent viremia in human immunodeficiency virus/hepatitis B coinfected patients undergoing long-term tenofovir: Virological and clinical implications
Authors: Anders Boyd, Joël Gozlan, Sarah Maylin, Constance Delaugerre, Gilles Peytavin, Pierre-Marie Girard, Fabien Zoulim, Karine Lacombe
Journal: Hepatology (2014)

Tenofovir (TDF) is considered the ideal treatment for patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV). However, certain coinfected patients exhibit incomplete viral suppression, with persistent, and sometimes transient, bouts of HBV replication. The reasons for this, including clinical effect, are unclear. A total of 111 HIV-HBV-infected patients undergoing TDF-containing antiretroviral therapy were prospectively followed. Serum HBV-DNA viral load, hepatitis surface (HBsAg) and e antigen (HBeAg) status were obtained at baseline and every 6-12 months. Amino acid (aa) changes on the polymerase gene were assessed using direct sequencing after nested polymerase chain reaction in patients with persistent viremia (PV). After a median of 74.7 months (interquartile range: 33.4-94.7), virological response (VR; &lt;60 IU/mL) occurred in 96 of 111 (86.5%) patients. Of these, 86 of 96 (89.6%) remained completely undetectable during follow-up (stabilized VR). The remaining 10 of 96 (10.4%) patients had a transient blip of detectable HBV-DNA (transient PV), during which time 9 of 9 (100%) with available samples had detectable plasma TDF. Low-level PV (LL-PV; 61-2,000 IU/mL) was observed in 11 of 111 (9.9%) patients, the majority of which had detectable plasma TDF (8 of 9; 88.9%). High-level PV (&gt;2,000 IU/mL) was rare (4 of 111; 3.6%) and was associated with nonadherence. At TDF initiation, patients with stabilized VR had significantly higher nadir CD4 + count, compared to those with transient PV ( P = 0.006) or LL-PV ( P = 0.04). No consistent aa changes, other than those associated with lamivudine resistance, were observed in patients with persistent viremia. Importantly, HBeAg loss, HBeAg seroconversion, and HBsAg loss only occurred in patients with stabilized VR. Two patients with stabilized VR developed hepatocellular carcinoma and 2 with LL PV died, 1 of a liver-related cause. Conclusion : Suboptimal HBV control during TDF treatment has a negative effect on serological outcomes, but not necessarily clinical events. Immunoregulation may provide more insight into this phenomenon. (Hepatology 2014;60:497–507)
Preventing depression in adolescents
Authors: S. N. Merry, K. Stasiak
Journal: BMJ (2012)

Requires a broad public health approach and refinement of interventions 

The individual and societal costs of depressive disorder have been well documented, and the arguments for depression prevention programmes are compelling.1 The prevalence of depression rises steeply in mid-adolescence, so schools are a logical place to deliver prevention programmes. Several studies have investigated the efficacy of interventions aimed at preventing depression in adolescents, and meta-analyses have provided encouraging results.2 However, many studies have had methodological difficulties, including lack of attention controls. 

In a linked paper (doi:10.1136/bmj.e6058), Stallard and colleagues have reported the results of a large well conducted pragmatic randomised trial.3 They compared the resourceful adolescent programme—a group programme delivered in schools and based on cognitive behavioural therapy that has shown evidence of effect in universal samples of school students—with an attention control or usual classes.4 5 Facilitators were well trained, and the study was also appropriately powered and had excellent retention and follow-up rates. However, no demonstrable effect was seen, and the findings suggest that the intervention programme may actually have led to an increase in depressive symptoms. These findings are worrying, especially when meta-analyses have shown that …
Prediction of Outcome Following Early Salvage Radiotherapy Among Patients with Biochemical Recurrence After Radical Prostatectomy
Authors: Alberto Briganti, R. Jeffrey Karnes, Steven Joniau, Stephen A. Boorjian, Cesare Cozzarini, Giorgio Gandaglia, Wolfgang Hinkelbein, Karin Haustermans, Bertrand Tombal, Shahrokh Shariat, Maxine Sun, Pierre I. Karakiewicz, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel
Journal: European Urology (2013)
Impact of point-of-care lactate measurement on mortality in critically-ill patients requiring mechanical ventilation
Authors: Kay Choong See, Joy Dizon, Malcolm Mahadevan, Tow Keang Lim, Jason Phua
Journal: European Respiratory Journal (2014)

Background. Lactate levels correlate with mortality and can guide the resuscitation of patients with severe sepsis. However, the wider impact of early, point-of-care lactate measurement (POC-Lac) in the emergency department (ED) for both septic and non-septic patients who require mechanical ventilation is unclear. We investigated the clinical outcomes of these patients who received POC-Lac in ED, compared to patients who did not.  Methods. Observational study of mechanically-ventilated patients admitted to a 20-bed medical intensive care unit (ICU) of a 1081-bed university hospital in 2010-2012. Resuscitation bundles according to the Surviving Sepsis Campaign guidelines were in place, though no equivalent protocols existed for non-septic conditions. Analyses for ICU and hospital mortality were controlled for sepsis diagnosis and other confounders.  Results. We studied 1,430 patients (age 61.2 ± 16.5 years, 39.7% female, 43.4% diagnosed with sepsis at ED, 26.6% ICU mortality, 32.5% hospital mortality). 609 patients (42.6%) had POC-Lac in the ED. POC-Lac was significantly associated with lower GCS score, systolic blood pressure and PaO2/FIO2 ratio. POC-Lac was also significantly associated with more therapy instituted in ED (intubation, vasopressors, antibiotics), more direct ED-to-ICU transfers, and decreased ICU (adjusted OR 0.64, 95% CI 0.48-0.88, P=0.005) and hospital mortality (adjusted OR 0.71, 95% CI 0.55-0.90, P=0.006).  Conclusions. Early, POC-Lac in ED was associated with earlier intensive therapy and improved survival in critically-ill patients requiring mechanical ventilation.
Ownership and Use of Tissue Specimens for Research
Authors: Rina Hakimian, David Korn
Journal: JAMA (2004)

Academic and industrial scientists have sharply increased their demand for properly prepared and clinically annotated tissue samples that yield valuable insights into the origins and expressions of human disease. Historically, research on human tissue samples has been relatively unencumbered by federal regulations and occurred without delineation of ownership rights to the specimens, patient data, or research products. As regulations have become increasingly restrictive, and because clear ownership interests have never been established, the presumed right of researchers and institutions to collect, use, and dispose of specimens and their associated patient data has remained undefined and occasionally contentious. Recent examination of these issues by a US federal court resulted in a ruling that individuals do not retain rights of ownership or control of biological materials contributed for research, regardless of whether commercial benefit accrues. This article examines the legal, regulatory, and ethical framework within which human tissue research is currently conducted. We contend that because the benefits of medical knowledge derived from tissue research potentially accrue to all individuals and future generations (rather than a single recipient), society may justify an expansive use of these valuable resources for future studies.
An Early Divergence of KhoeSan Ancestors from Those of Other Modern Humans Is Supported by an ABC-Based Analysis of Autosomal Resequencing Data
Authors: Krishna R. Veeramah, Daniel Wegmann, August Woerner, Fernando L. Mendez, Joseph C. Watkins, Giovanni Destro-Bisol, Himla Soodyall, Leslie Louie, Michael F. Hammer
Journal: Molecular Biology and Evolution (2011)

Sub-Saharan Africa has consistently been shown to be the most genetically diverse region in the world. Despite the fact that a substantial portion of this variation is partitioned between groups practicing a variety of subsistence strategies and speaking diverse languages, there is currently no consensus on the genetic relationships of sub-Saharan African populations. San (a subgroup of KhoeSan) and many Pygmy groups maintain hunter-gatherer lifestyles and cluster together in autosomal-based analysis, whereas non-Pygmy Niger-Kordofanian speakers (non-Pygmy NKs) predominantly practice agriculture and show substantial genetic homogeneity despite their wide geographic range throughout sub-Saharan Africa. However, KhoeSan, who speak a set of relatively unique click-based languages, have long been thought to be an early branch of anatomically modern humans based on phylogenetic analysis. To formally test models of divergence among the ancestors of modern African populations, we resequenced a sample of San, Eastern, and Western Pygmies and non-Pygmy NKs individuals at 40 nongenic (∼2 kb) regions and then analyzed these data within an Approximate Bayesian Computation (ABC) framework. We find substantial support for a model of an early divergence of KhoeSan ancestors from a proto-Pygmy-non-Pygmy NKs group ∼110 thousand years ago over a model incorporating a proto-KhoeSan–Pygmy hunter-gatherer divergence from the ancestors of non-Pygmy NKs. The results of our analyses are consistent with previously identified signals of a strong bottleneck in Mbuti Pygmies and a relatively recent expansion of non-Pygmy NKs. We also develop a number of methodologies that utilize "pseudo-observed" data sets to optimize our ABC-based inference. This approach is likely to prove to be an invaluable tool for demographic inference using genome-wide resequencing data.
Differences in plasma and sputum biomarkers between COPD and COPD-asthma overlap
Authors: Hiroshi Iwamoto, Jing Gao, Jukka Koskela, Vuokko Kinnula, Hideo Kobayashi, Tarja Laitinen, Witold Mazur
Journal: European Respiratory Journal (2013)

The pathophysiological features of chronic obstructive pulmonary disease ( COPD)–asthma overlap are poorly understood and there has been no study of plasma or sputum biomarkers in overlap patients. In order to clarify the similarity and differences between overlap and COPD or asthma, we have investigated four potential biomarkers of COPD: surfactant protein A (SP-A), soluble receptor for advanced glycation end-products (sRAGE), myeloperoxidase (MPO) and neutrophil gelatinase-associated lipocalin (NGAL). SP-A and sRAGE are pneumocyte-derived markers. MPO and NGAL are neutrophil-derived molecules, but NGAL can also be expressed by respiratory epithelial cells. Plasma levels of SP-A and sRAGE and induced sputum levels of MPO and NGAL were measured by enzyme immunoassay/ELISA in 134 subjects: nonsmokers (n=26), smokers (n=23), asthma (n=32), COPD (n=39) and COPD–asthma overlap patients (n=14). In patients with COPD–asthma overlap, sputum MPO and plasma SP-A were significantly elevated whereas plasma sRAGE levels were reduced compared with asthma patients. Only sputum NGAL was significantly elevated in COPD–asthma overlap compared with COPD (p=0.00016) and could be used to differentiate patients with overlap from those with COPD. Increased induced sputum levels of NGAL might be a characteristic feature of overlap, suggesting enhanced neutrophilic airway inflammation and/or airway epithelial injury in COPD–asthma overlap.
Blood-Borne Pathogens in Sports
Authors: Jouko Karjalainen
Journal: Annals of Internal Medicine (1995)

Letters15 October 1995Blood-Borne Pathogens in SportsJouko Karjalainen, MD and Goran Friman, MDJouko Karjalainen, MDCentral Military Hospital, Helsinki, Finland; Uppsala University Hospital, Uppsala, SwedenSearch for more papers by this author and Goran Friman, MDCentral Military Hospital, Helsinki, Finland; Uppsala University Hospital, Uppsala, SwedenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-8-199510150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:In their timely article, Mast and colleagues [1] stated that the only outbreak of hepatitis B in sports reported in the medical literature was that seen among sumo wrestlers in Japan in 1980. However, a much larger epidemic occurred among Swedish orienteers (track-finders) in the early 1960s [2]. In that epidemic, more than 600 infected competitors had clinical symptoms, and at least as many subclinical cases occurred. Some cases were also found among orienteers in Norway and Finland. Because no serologic test for hepatitis was available at that time, the orienteers' hepatitis was initially considered a distinct ...References1. Mast EE, Goodman RA, Bond WW, Favero MS, Drotman DP. Transmission of blood-borne pathogens during sports: risk and prevention. Ann Intern Med. 1995; 122:283-5. Google Scholar2. Ringertz O, Zetterberg B. Serum hepatitis among Swedish track-finders. An epidemiologic study. N Engl J Med. 1967; 276:540-6. Google Scholar3. Berg R, Ringertz O, Espmark A. Australia antigen in hepatitis among Swedish track-finders. Acta Pathol Microbiol Scand. 1971; 79:423-7. Google Scholar Author, Article, and Disclosure InformationAuthors: Jouko Karjalainen, MD; Goran Friman, MDAffiliations: Central Military Hospital, Helsinki, Finland; Uppsala University Hospital, Uppsala, Sweden PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byPrevalence of Hepatitis B, Hepatitis C and HIV and Related Risk Factors in Contact Sportsmen in Zanjan: A Letter to EditorSports: The Infectious HazardsHígado y deporte 15 October 1995Volume 123, Issue 8Page: 635-636KeywordsBloodHepatitisHepatitis AHepatitis BHepatitis B virusPathogensRacial and ethnic issuesSports ePublished: 15 August 2000 Issue Published: 15 October 1995 Copyright & PermissionsCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Functional and structural changes in the rabbit ear artery after sympathetic denervation.
Authors: R D Bevan, H Tsuru
Journal: Circulation Research (1981)

We studied the tissue weight, dimensions, contractility, elasticity, and sensitivity to exogenous norepinephrine (NE) of denervated and innervated segments of the central ear arteries of white New Zealand rabbits. Three different age groups received unilateral superior cervical ganglionectomies, "growing" at 3-4 weeks, "young adult" at 9-11 weeks, and "mature" at 16-20 weeks. In the growing group, 8 weeks after ganglionectomy, the denervated arteries showed mean decreases in tissue weight (11%), total wall thickness (12+), cross-sectional area of media (17%), contractility (16%), and increases in the tangential modulus of elasticity and sensitivity to NE (2.3-fold) compared to the contralateral control vessels. The change in medial cross-sectional area was significant in the growing and young adult but not the mature animals. The other changes, however, although consistently seen, differed quantitatively among the groups. These results indicate that an intact innervation is necessary for normal development and maintenance of the artery wall. However, the precise consequences of this influence vary at different ages. Whether this influence involves a special trophic factor is not known.