tbuckley/cabot-search huggingface dataset:
Effectivity of current sterility methods for transgastric NOTES procedures: results of a randomized porcine study
Authors: A. Eickhoff, S. Vetter, D. von Renteln, K. Caca, G. Kähler, J. Eickhoff, R. Jakobs, J. Riemann
Journal: Endoscopy (2010)

Natural-orifice transluminal endoscopic surgery (NOTES) is an emerging transluminal technique in which interventions are carried out by entering the abdominal cavity via a natural orifice such as the stomach. Infection is a potential risk of the procedure, and the potential pathogens are different from those encountered with skin incisions. Currently, available data regarding prophylactic anti-infective treatment are limited. We compared the effectiveness of topical antimicrobial lavage of mouth and stomach and proton pump inhibitor therapy with gastric cleansing with sterile saline solution in preventing NOTES-related contamination and infection.A randomized survival swine study was performed. Eight pigs underwent preparation with intravenously administered proton pump inhibitors, mouth and gastric lavage (chlorhexidine), and gastric irrigation (diluted neomycin), plus single-shot intravenous antibiotics. Control group (n = 8) underwent gastric cleansing with sterile saline solution. Peritoneal biopsy, multiple smears, and dilutions for cultures were taken and incubated. The swine were sacrificed after 14 days. Bacterial load was expressed in colony-forming units (CFU).One pig died due to gallbladder perforation after 3 days, 2/15 swine presented minor clinical signs of infection in the 14-day follow-up (all 3 pigs were in the control group). Mean C-reactive protein levels were 5.7 +/- 2.4 g/dL (therapy group) and 12.2 +/- 3.8 g/dL (control) ( P = 0.17). Bacterial growth was seen in 1/8 swine (therapy group) and 6/8 swine (control group) ( P = 0.002). Bacterial load was 282 CFU/mL (therapy) vs. 3.2 x 10 (5) CFU/mL (control) ( P = 0.023) in the follow-up.The use of intravenous antibiotics in addition to topical antimicrobial lavage of mouth and stomach and treatment with proton pump inhibitors decreased the peritoneal bacterial load to almost zero and this was associated with a significantly lower peritoneal infection rate compared with saline-only lavage.
Cell-mediated immunity in pigeon breeders' lung: the effect of removal from antigen exposure
Authors: MA Johnson, A Nemeth, A Condez, SW Clarke, LW Poulter
Journal: European Respiratory Journal (1989)

Eighteen precipitin-positive pigeon breeders, thirteen symptomatic (SPB), with extrinsic allergic alveolitis (EAA), and five asymptomatic (APB), without lung disease, underwent bronchoalveolar lavage (BAL). Cytospins were prepared on which differential cell counts were performed. Immunocytological methods, using monoclonal antibodies, were performed to identify lymphocyte and macrophage subsets. Marked abnormalities in cell populations were observed in both groups but with no suggestion of differences between the groups. All subjects had a lymphocytosis in BAL (SPB 45%; APB 29%). These lymphocytes were almost exclusively T-cells. The cluster designation CD4/CD8 ratio was decreased (SPB 0.86; APB 1.13) and a significantly higher proportion of these cells than normal expressed UCHL1 (an antigen associated with the common leucocyte antigen complex) indicating immune commitment. In the macrophage population increased proportions of cells expressing antigens associated with interdigitating cells (RFD1+) and mature macrophages (RFD7+) were also abnormal. When six SPB patients were relavaged after isolation from pigeons for three weeks, there was a significant reduction in the lymphocytosis and in the proportion of UCHL1+ lymphocytes. This was accompanied by reductions in the percentage of macrophages expressing RFD1 and UCHL1. We suggest that EAA in pigeon breeders is associated with a cell-mediated immune response which is down-regulated by isolating patients from exposure to pigeon derived antigens.
Medications for Risk Reduction of Primary Breast Cancer in Women: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A. Moyer
Journal: Annals of Internal Medicine (2013)

Description: Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation on the use of medications for breast cancer risk reduction. Methods: The USPSTF reviewed evidence on the effectiveness, adverse effects, and subgroup variations of medications to reduce the risk for breast cancer—specifically, the selective estrogen receptor modulators tamoxifen and raloxifene. The USPSTF also reviewed a meta-analysis of placebo-controlled trials to understand the relative benefits and harms of tamoxifen and raloxifene. Population: This recommendation applies to asymptomatic women aged 35 years or older without a prior diagnosis of breast cancer, ductal carcinoma in situ, or lobular carcinoma in situ. Recommendation: The USPSTF recommends that clinicians engage in shared, informed decision making with women who are at increased risk for breast cancer about medications to reduce their risk. For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen or raloxifene. (B recommendation) The USPSTF recommends against the routine use of medications, such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. (D recommendation)
In vitro generation of human cytotoxic lymphocytes by virus. Viral glycoproteins induce nonspecific cell-mediated cytotoxicity without release of interferon.
Authors: P Casali, J G Sissons, M J Buchmeier, M B Oldstone
Journal: The Journal of Experimental Medicine (1981)

Purified hemagglutinin and fusion glycoproteins of measles virus either in soluble form or inserted in artifical membranes bind to human peripheral blood lymphocytes and induce cell-mediated cytotoxicity (CMC) in a dose-response fashion. Both autologous and heterologous noninfected target cells are lysed in vitro. The expression of CMC is not inhibited by anti-measles virus antibody added to lymphocytes previously exposed to viral glycoproteins. THe killer lymphocytes are Fc receptor positive, both erythrocyte-rosetting and non-erythrocyte-rosetting, as assessed by both positive and negative selection experiments. The induction of nonspecific CMC by viral glycoproteins either in the soluble state or inserted into artificial membranes could be segregated from the CMC associated with whole virions. First, on kinetics studies, purified viral glycoproteins induced CMC more rapidly than did whole virus. Second, viral glycoprotein-produced response occurred in the absence of detectable release of interferon into the culture medium, whereas CMC activity due to whole virions was associated with interferon release. The fact that purified measles virus glycoproteins integrated into artificial membrane bilayers were as efficient as their soluble counterparts in inducing CMC suggests that the hydrophobic portion of the glycoproteins was not involved in the induction and expression of the lytic activity. Purified glycoproteins from lymphocytic choriomeningitis virus behave similarly, although this virus is unrelated to measles virus. It is inferred that interferon-independent CMC induced by viral glycoproteins might account for some of the biological reactions occurring early in the control of a viral infection.
What should it take to describe a substance or product as 'sperm-safe'
Authors: D. Mortimer, C. L. R. Barratt, L. Bjorndahl, C. de Jager, A. M. Jequier, C. H. Muller
Journal: Human Reproduction Update (2013)

Male reproductive potential continues to be adversely affected by many environmental, industrial and pharmaceutical toxins. Pre-emptive testing for reproductive toxicological (side-)effects remains limited, or even non-existent. Many products that come into direct contact with spermatozoa lack adequate testing for the absence of adverse effects, and numerous products that are intended for exposure to spermatozoa have only a general assumption of safety based on the absence of evidence of actual harm. Such assumptions can have unfortunate adverse impacts on at-risk individuals (e.g. couples who are trying to conceive), illustrating a clear need for appropriate up-front testing to establish actual 'sperm safety'.After compiling a list of general areas within the review's scope, relevant literature and other information was obtained from the authors' personal professional libraries and archives, and supplemented as necessary using PubMed and Google searches. Review by co-authors identified and eliminated errors of omission or bias.This review provides an overview of the broad range of substances, materials and products that can affect male fertility, especially through sperm fertilizing ability, along with a discussion of practical methods and bioassays for their evaluation. It is concluded that products can only be claimed to be 'sperm-safe' after performing objective, properly designed experimental studies; extrapolation from supposed predicate products or other assumptions cannot be trusted.We call for adopting the precautionary principle, especially when exposure to a product might affect not only a couple's fertility potential but also the health of resulting offspring and perhaps future generations.
Deleterious effects of short-term, high-intensity exercise on immune function: evidence from leucocyte mitochondrial alterations and apoptosis
Authors: T-C Tuan, T-G Hsu, M-C Fong, C-F Hsu, K K C Tsai, C-Y Lee, C-W Kong
Journal: British Journal of Sports Medicine (2007)

Although moderate exercise can benefit health, acute and vigorous exercise may have the opposite effect. Strenuous exercise can induce alterations in the physiology and viability of circulating leucocytes, which have a causal relationship with exercise-induced immune distress.To investigate the use of mitochondrial transmembrane potential (MTP), a functional marker of the energy and viability status of leucocytes, for monitoring the immunomodulating effects of short-term, high-intensity exercise.12 healthy volunteers with a mean Vo(2)max of 70.4 ml/kg/min carried out 3 consecutive days of high-intensity exercise (85% of Vo(2)max for 30 min every day). Blood samples were collected at multiple time points immediately before and after each exercise session and at 24 and 72 h after the completion of exercise. Leucocyte MTP, apoptosis and circulatory inflammation markers were measured by flow cytometry and enzyme-linked immunosorbent assays.MTP of peripheral blood leucocytes had declined immediately after the first exercise session and remained subnormal 24 h later. It did not normalise until 72 h after exercise. The sequential changes in MTP were consistent among the three leucocyte subpopulations (polymorphonuclear neutrophils, lymphocytes and monocytes) and were significant (p<0.05). Leucocytes displayed a gradual and incremental change in their propensity for apoptosis during and after exercise. Similarly, plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand were raised during the exercise sessions and had not normalised by 72 h after the completion of exercise. Correlation between changes in leucocyte MTP and plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand was variable, but significant for polymorphonuclear neutrophils and lymphocytes (p<0.05).Short-term, high-intensity exercise can lead to a significant and prolonged dysfunction of the mitochondrial energy status of peripheral blood leucocytes, which is accompanied by an increased propensity for apoptosis and raised pro-inflammatory mediators. These results support the immunosuppressive effects of excessive exercise and suggest that MTP is a useful marker of these effects.
IL-6 and Ovarian Cancer—Response
Authors: Frances R. Balkwill, Jermaine Coward, Hagen Kulbe, Carla Milagre, Ganga Gopinathan, Iain A. McNeish
Journal: Clinical Cancer Research (2011)

In their letter, Locasale and Zeskind hypothesize that anti-interleukin (IL)-6 therapies may be of most benefit in patients with cancer who have low levels of epidermal growth factor (EGF) signaling in their tumors and also that a combination of anti-IL-6 and EGF receptor (EGFR) inhibitors might have clinical benefit in those patients where high EGFR signaling drives the disease. Their hypothesis is based on the following findings:Locasale and Zeskind have made an interesting connection that is worthy of further study. However, there are a number of complexities that may influence the potential association between IL-6 and EGFR signaling in cancer.See the original Letter to the Editor, p. 7837No potential conflicts of interest were disclosed.
Aspects of the release of superoxide by leukocytes, and a means by which this is switched off.
Authors: M L Karnovsky, A Bishop, V C Camerero, M A Paz, P Colepicolo, J M Ribeiro, P M Gallop
Journal: Environmental Health Perspectives (1994)

Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (O2-), it is possible that a component or components, might have been overlooked. Furthermore, O2- production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off O2- production by stimulated leukocytes. This article offers evidence that methoxatin (PQQ), a redox-cycling orthoquinone, might be involved in O2- production by leukocytes. This is based on the fact that inhibitors of O2- production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored O2- release. With respect to turning off cellular O2- release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked O2- release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.
The Effects of On-Duty Napping on Intern Sleep Time and Fatigue
Authors: Vineet Arora, Carrie Dunphy, Vivian Y. Chang, Fawaz Ahmad, Holly J. Humphrey, David Meltzer
Journal: Annals of Internal Medicine (2006)

Background: Naps during extended work shifts are effective in reducing fatigue in other industries, but the use of a nap as a countermeasure to prevent fatigue in residents is uncertain. Objective: To assess the effects of a call-night nap on resident sleep and fatigue. Design: 1-year, within-participant, paired trial with crossover at midmonth. Setting: Academic teaching hospital. Participants: 38 of 40 internal medicine interns. Measurements: Sleep was measured by using wristwatch actigraphy. By using the experience sampling method on a personal digital assistant, random alerts prompted interns to rate fatigue on the 7-point Stanford Sleepiness Scale (7 is most tired). Hospital paging logs and structured interviews provided information on use of coverage. Intervention: For 2 weeks of every month, interns were assigned to the nap schedule, which provided coverage to on-duty interns from midnight to 7:00 a.m. so that they could finish their work and take a nap. The other 2 weeks of the month constituted a standard schedule. Results: Interns received 41 more minutes of sleep while on call with the nap schedule (185 minutes vs. 144 minutes; P < 0.001). When interns with the nap schedule used coverage, they received 68 more minutes of sleep (210 minutes vs. 142 minutes; P < 0.001). Despite these small increases in sleep, interns reported less overall fatigue while on the nap schedule than while on the standard schedule (1.74 vs. 2.26; P = 0.017). Postcall fatigue with the nap schedule was lower by nearly 1 point (2.23 vs 3.16; P = 0.036), which is almost equivalent to the difference between on-call and postcall fatigue with the standard schedule (2.06 vs. 3.16). However, use of coverage by interns on the nap schedule was impaired by their desire to care for their patients and concerns about discontinuity of care. Limitations: This was a single-institution study that did not have the power to examine outcomes related to intern or patient well-being. Conclusions: Coverage to allow a nap during an extended duty-hour shift can increase sleep and decrease fatigue for residents.
Effect of Microtubule Inhibitors on Malignant Invasion In Vitro&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Marc M. K. Mareel, Marc J. de Brabander
Journal: JNCI Journal of the National Cancer Institute (1978)

The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 μg/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 μg/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 μg/ml) plus the microtubule inhibitor Nocodazole (1 μg/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 μg/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.
Early serial trough and antidrug antibody level measurements predict clinical outcome of infliximab and adalimumab treatment: Table 1
Authors: N Vande Casteele, V Ballet, G Van Assche, P Rutgeerts, S Vermeire, A Gils
Journal: Gut (2011)

We read with great interest the recent article by Ben-Horin et al which concludes that the measurement of trough levels of infliximab (TLI) combined with the measurement of antibodies to infliximab (ATI) is highly correlated with the clinical response to the therapeutic.1

Infliximab (Remicade) and adalimumab (Humira), both monoclonal antibodies towards TNF-α, are widely used in the treatment of Crohn's disease and ulcerative colitis. Loss of efficacy, infusion and injection-site reactions and hypersensitivity reactions have been described due to the development of antibodies towards these agents.2 We agree with Ben-Horin et al that the interpretation of ATI with TLI is important to document the clinical response of a patient to infliximab. However, we urge that these measurements are performed early in the treatment. Previously it was stated that the TLI measured early after …
A meta-analysis of genome-wide association studies identifies novel variants associated with osteoarthritis of the hip
Authors: Evangelos Evangelou, Hanneke J Kerkhof, Unnur Styrkarsdottir, Evangelia E Ntzani, Steffan D Bos, Tonu Esko, Daniel S Evans, Sarah Metrustry, Kalliope Panoutsopoulou, Yolande F M Ramos, Gudmar Thorleifsson, Konstantinos K Tsilidis, Nigel Arden, Nadim Aslam, Nicholas Bellamy, Fraser Birrell, Francisco J Blanco, Andrew Carr, Kay Chapman, Aaron G Day-Williams, Panos Deloukas, Michael Doherty, Gunnar Engström, Hafdis T Helgadottir, Albert Hofman, Thorvaldur Ingvarsson, Helgi Jonsson, Aime Keis, J Christiaan Keurentjes, Margreet Kloppenburg, Penelope A Lind, Andrew McCaskie, Nicholas G Martin, Lili Milani, Grant W Montgomery, Rob G H H Nelissen, Michael C Nevitt, Peter M Nilsson, William ER Ollier, Neeta Parimi, Ashok Rai, Stuart H Ralston, Mike R Reed, Jose A Riancho, Fernando Rivadeneira, Cristina Rodriguez-Fontenla, Lorraine Southam, Unnur Thorsteinsdottir, Aspasia Tsezou, Gillian A Wallis, J Mark Wilkinson, Antonio Gonzalez, Nancy E Lane, L Stefan Lohmander, John Loughlin, Andres Metspalu, Andre G Uitterlinden, Ingileif Jonsdottir, Kari Stefansson, P Eline Slagboom, Eleftheria Zeggini, Ingrid Meulenbelt, John PA Ioannidis, Tim D Spector, Joyce B J van Meurs, Ana M Valdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Osteoarthritis (OA) is the most common form of arthritis with a clear genetic component. To identify novel loci associated with hip OA we performed a meta-analysis of genome-wide association studies (GWAS) on European subjects. <h3>Methods</h3> We performed a two-stage meta-analysis on more than 78 000 participants. In stage 1, we synthesised data from eight GWAS whereas data from 10 centres were used for 'in silico' or 'de novo' replication. Besides the main analysis, a stratified by sex analysis was performed to detect possible sex-specific signals. Meta-analysis was performed using inverse-variance fixed effects models. A random effects approach was also used. <h3>Results</h3> We accumulated 11 277 cases of radiographic and symptomatic hip OA. We prioritised eight single nucleotide polymorphism (SNPs) for follow-up in the discovery stage (4349 OA cases); five from the combined analysis, two male specific and one female specific. One locus, at 20q13, represented by rs6094710 (minor allele frequency (MAF) 4%) near the <i>NCOA3</i> (nuclear receptor coactivator 3) gene, reached genome-wide significance level with p=7.9×10<sup>−9</sup> and OR=1.28 (95% CI 1.18 to 1.39) in the combined analysis of discovery (p=5.6×10<sup>−8</sup>) and follow-up studies (p=7.3×10<sup>−4</sup>). We showed that this gene is expressed in articular cartilage and its expression was significantly reduced in OA-affected cartilage. Moreover, two loci remained suggestive associated; rs5009270 at 7q31 (MAF 30%, p=9.9×10<sup>−7</sup>, OR=1.10) and rs3757837 at 7p13 (MAF 6%, p=2.2×10<sup>−6</sup>, OR=1.27 in male specific analysis). <h3>Conclusions</h3> Novel genetic loci for hip OA were found in this meta-analysis of GWAS.
INDOCYANINE GREEN: OBSERVATIONS ON ITS PHYSICAL PROPERTIES, PLASMA DECAY, AND HEPATIC EXTRACTION*
Authors: Gilbert R. Cherrick, Samuel W. Stein, Carroll M. Leevy, Charles S. Davidson
Journal: Journal of Clinical Investigation (1960)

Indocyanine green 1 (ICG) is a tricarbocyanine dye (Figure 1) which has been used in the indi- cator dilution technique for measuring cardiac output (1, 2).Animal studies (3) and prelimi- nary observations of human subjects (4, 5) have suggested that this dye may have characteristics that could make its uptake, storage, and excretion by the liver helpful indices of hepatic function.The present investigations were carried out to determine whether indocyanine green has proper- ties that may render it suitable for assessing liver function and hepatic blood flow in man.METHODS AND PROCEDURES Physical properties.Indocyanine green was prepared for intravenous administration by dissolving the dye in distilled water to a concentration of 5 mg per ml.Read- ings of dye concentration were made in a Beckman DU spectrophotometer at 815 m/1.Volume of distribution of radioiodinated human serum albumin 2 was compared with the initial volume of dis- tribution of ICG in 4 normal subjects.Each subject was given approximately 20 /Ac of the I3"-labeled albumin and 50 mg of ICG in a rapid intravenous injection.Ve- nous