tbuckley/cabot-search huggingface dataset:
Inhibition of Tissue Factor–Mediated Coagulation Markedly Attenuates Stenosis After Balloon-Induced Arterial Injury in Minipigs
Authors: Luigi Oltrona, Christopher M. Speidel, Dino Recchia, Samuel A. Wickline, Paul R. Eisenberg, Dana R. Abendschein
Journal: Circulation (1997)

Background Exposure and upregulation of tissue factor in the wall of balloon-injured arteries may result in prolonged activation of coagulation contributing to restenosis. This study was designed to determine whether brief or more prolonged inhibition of tissue factor–mediated coagulation with tissue factor pathway inhibitor (TFPI) attenuates neointimal formation and luminal stenosis after balloon-induced arterial injury. Methods and Results The carotid artery of minipigs fed an atherogenic diet was injured by repetitive balloon hyperinflations, a procedure that rapidly yields complex, plaque-like neointimal lesions and high-grade luminal stenosis. Recombinant TFPI (rTFPI) was administered intravenously beginning 15 minutes before balloon injury as either a high dose (0.5 mg/kg bolus and 100 μg·kg −1 ·min −1 ) for 3 hours (n=7) or 24 hours (n=6) or as a low dose (0.5 mg/kg and 25 μg·kg −1 ·min −1 ) for 24 hours (n=6). Control animals received intravenous heparin (100 U·kg −1 ·h −1 ) for 3 hours (n=6) or 24 hours (n=7) or aspirin (5 mg/kg PO) followed by heparin for 24 hours (n=7). Luminal stenosis, assessed histologically 4 weeks after injury, was 73±17% and 76±18% (mean±SEM) in animals that received rTFPI or heparin for 3 hours, respectively. In contrast, luminal stenosis was only 11±12% and 6±3% in pigs given high and low doses, respectively, of rTFPI for 24 hours compared with 46±22% in pigs given heparin for 24 hours and 40±19% in those given both heparin and aspirin ( P &lt;.0002). Conclusions Inhibition of tissue factor–mediated coagulation during the first 24 hours after deep arterial injury appears to be particularly effective for attenuating subsequent neointimal formation and stenosis.
Lamarck, Artificial Intelligence (AI), and belief
Authors: Yorick Wilks
Journal: Behavioral and Brain Sciences (2009)

Abstract Nothing in McKay &amp; Dennett's (M&amp;D's) target article deals with the issue of how the adaptivity, or some other aspect, of beliefs might become a biological adaptation; which is to say, how the functions discussed might be coded in such a way in the brain that their development was also coded in gametes or sex transmission cells.
Do adverts subvert? Are bacteria good for us?
Authors: Douglas Kamerow
Journal: BMJ (2007)

Do drug advertisements (“adverts” in Britspeak) belong in medical journals? In a head to head debate in this week's issue, Richard Smith, former BMJ editor and long-time critic of big pharma, says yes (doi: 10.1136/bmj.39259.472998.AD). He maintains, perhaps paradoxically, that advertising allows journals to be independent and thus better. Major journals have advertising from many manufacturers and thus no one company can exert undue pressure or influence. Smith's big concern is one that most readers don't even think about: the lucrative …
Important Features in an Industrial Medical Program
Authors: George F. Wilkins
Journal: New England Journal of Medicine (1952)

A MEDICAL program applied to a specific industry should be tailored to fit the needs of that industry. The nature of the industry, its size and its geography are important factors in the selection of the parts of a health program that deserve special emphasis. The operations of a chemical plant, for example, require careful attention to the problems of toxic exposure, whereas a heavy manufacturing industry has as its major problem, the prevention and care of trauma. However, people are still hurt in chemical and poisoned in heavy manufacturing industries, and these hazards exist regardless of whether the industry . . .
Sphingosylphosphorylcholine stimulates contraction of fibroblast-embedded collagen gel
Authors: K.B. Suhr, R. Tsuboi, H. Ogawa
Journal: British Journal of Dermatology (2000)

Sphingosylphosphorylcholine (SPC), a sphingolipid metabolite, has recently been reported to stimulate wound healing in an animal model. To clarify the mechanism of SPC on the healing process, we examined the effect of SPC on wound contraction using an in vitro model. A mixture of human dermal fibroblasts and porcine type I collagen in a serum-free medium was gelled, and then separated from the well after a 12-h incubation. Various reagents were applied to the medium, and its contractile activity was analysed by measuring the amount of contracted surface area. Among the sphingolipid metabolites, SPC and sphingosine-1-phosphate, but not sphingosine, C2-ceramide and C6-ceramide, stimulated collagen gel contraction. Maximal gel contraction, observed at 10 micromol L-1 of SPC, occurred as early as 1 h after the treatment and persisted for more than 48 h. The effect of SPC was not inhibited by pretreatment with antitransforming growth factor-beta or antiplatelet-derived growth factor-BB antibodies. Among the various signal transduction inhibitors, pertussis toxin, staurosporine and H7 were found to inhibit the action of SPC, whereas genistein and tyrphostin A47 were not, suggesting that fibroblast contraction induced by SPC is mediated by a trimeric guanosine triphosphate-binding protein (G protein)-coupled receptor and protein kinase. Our findings imply that the effect of SPC as a healing stimulant might be due in part to stimulation of fibroblast contraction in granulation tissue.
Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.
Authors: W Qi, R J Reiter, D X Tan, J J Garcia, L C Manchester, M Karbownik, J R Calvo
Journal: Environmental Health Perspectives (2000)

Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.
Convalescence After Herniorrhaphy
Authors: J. D. H. Iles
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Kerry's recent LETTER (<b>218</b>:740, 1971) about repair and convalescence after inguinal herniorrhaphy leaves an impression that should be corrected. We would agree with Kerry that, generally speaking, the most strenous activities—those involving maximum effort—are better postponed until four weeks have elapsed from operation; thus, a National Hockey League player would be well advised to wait that long before resuming his regular schedule, and so would pianomovers, stevedores, and lumber jacks. However, after saying "... no participation in strenous activities, including athletics, until one month after operative repair of a hernia..." Kerry goes on: "... and then the activity should increase gradually over one to two weeks." This is certainly over-cautious if it means that a hockey player, for example, should not resume skating and practicing until the four-week period is over; a well-known star whose hernia we repaired in 1970 resumed skating (with our blessing) within a
Prophylactic Treatment of Migraine With an Angiotensin II ReceptorBlocker
Authors: Erling Tronvik, Lars J. Stovner, Grethe Helde, Trond Sand, Gunnar Bovim
Journal: JAMA (2003)

<h3>Context</h3> There is a paucity of effective, well-tolerated drugs available for migraine prophylaxis. <h3>Objective</h3> To determine whether treatment with the angiotensin II receptor blocker candesartan is effective as a migraine-prophylactic drug. <h3>Design and Setting</h3> Randomized, double-blind, placebo-controlled crossover study performed in a Norwegian neurological outpatient clinic from January 2001 to February 2002. <h3>Patients</h3> Sixty patients aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly from newspaper advertisements. <h3>Interventions</h3> A placebo run-in period of 4 weeks was followed by two 12-week treatment periods separated by 4 weeks of placebo washout. Thirty patients were randomly assigned to receive one 16-mg candesartan cilexetil tablet daily in the first treatment period followed by 1 placebo tablet daily in the second period. The remaining 30 received placebo followed by candesartan. <h3>Main Outcome Measures</h3> The primary end point was number of days with headache; secondary end points included hours with headache, days with migraine, hours with migraine, headache severity index, level of disability, doses of triptans, doses of analgesics, acceptability of treatment, days of sick leave, and quality-of-life variables on the Short Form 36 questionnaire. <h3>Results</h3> In a period of 12 weeks, the mean number of days with headache was 18.5 with placebo vs 13.6 with candesartan (<i>P</i>= .001) in the intention-to-treat analysis (n = 57). Some secondary end points also favored candesartan, including hours with headache (139 vs 95;<i>P</i>&lt;.001), days with migraine (12.6 vs 9.0;<i>P</i>&lt;.001), hours with migraine (92.2 vs 59.4;<i>P</i>&lt;.001), headache severity index (293 vs 191;<i>P</i>&lt;.001), level of disability (20.6 vs 14.1;<i>P</i>&lt;.001) and days of sick leave (3.9 vs 1.4;<i>P</i>= .01), although there were no significant differences in health-related quality of life. The number of candesartan responders (reduction of ≥50% compared with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57 for days with migraine. Adverse events were similar in the 2 periods. <h3>Conclusion</h3> In this study, the angiotensin II receptor blocker candesartan provided effective migraine prophylaxis, with a tolerability profile comparable with that of placebo.
US stroke legislation is revised after <i>BMJ</i> airs controversy
Authors: Jeanne Lenzer
Journal: BMJ (2004)

Controversial federal legislation that would have designated hospitals as “stroke centres” only if they were prepared to administer alteplase for acute stroke has been radically altered.

A revised version of the Stroke Treatment and Ongoing Prevention Act, sponsored by Congresswoman Lois Capps, passed the US House Energy and Commerce Committee and will move to the full House of Representatives for a vote.

Provisions in the legislation that focused on getting patients to designated hospitals for treatment with alteplase were deleted. Funding for the entire five year programme was cut from approximately $665m (£360m; €540m) to $95m. Up to seven grants totalling $50m …
Some considerations concerning neurological development and psychometric assessment
Authors: James C. Kaufman, Alan S. Kaufman
Journal: Behavioral and Brain Sciences (2006)

Blair makes a strong case that fluid cognition and psychometric g are not identical constructs. However, he fails to mention the development of the prefrontal cortex, which likely makes the Gf– g distinction different in children than in adults. 1 He also incorrectly states that current IQ tests do not measure Gf; we discuss several recent instruments that measure Gf quite well.
Publication Bias and Dissemination of Clinical Research
Authors: C. B Begg, J. A Berlin
Journal: JNCI Journal of the National Cancer Institute (1989)

Publication bias is a widely recognized phenomenon that occurs because of the influence of study results on the chances of publication. Usually, studies with positive results are more likely to be published than studies with negative results, which leads to a preponderance of false-positive results in the literature. Empiric studies have demonstrated that the induced bias is large and can have a serious impact on meta-analyses, in which data from several studies are aggregated, as well as on informal reviews. The problem is deeply embedded in current research practice, which encourages demonstration of statistical significance to "prove" theories, and one of its causes is the pressure to publish extensively that is an integral part of the competition for academic promotion. Serious efforts to reduce this problem will involve restructuring the process by which study results are disseminated, changing editorial policies, and altering the style and methods of statistical analysis.
FDA Gets Feedback on Informed Consent Waiver
Authors: Charles Marwick
Journal: JAMA (1996)

LAST SEPTEMBER, the Food and Drug Administration (FDA) invited comment on a new proposal for exceptions from the requirement for obtaining informed consent of patients when testing new drugs or devices during medical emergencies. Now those responses are in, and while most generally support the proposal, many respondents expressed reservations and suggested changes in its details. The proposal, aimed at facilitating research while at the same time protecting the patients involved, describes how and under what circumstances exceptions from consent for this type of research could be granted when patients are unable to give consent because of their medical condition. The FDA had issued its proposal (<i>JAMA</i>. 1995;274:1184-1185) in light of increasing concerns that strict interpretation of current regulations intended to protect human subjects from research-related risks was jeopardizing certain types of studies—clinical trials of new drugs or devices used in life-threatening situations when the patients are unable to give
Age-related changes in bronchial hyperreactivity to methacholine in asthmatic children.
Authors: H Mochizuki, M Shigeta, M Kato, S Maeda, T Shimizu, A Mirokawa
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

To evaluate the influence of aging on bronchial hyperreactivity (BHR) during the childhood period, age-related changes in bronchial reactivity to methacholine (BRm) in children from 2 to 13 yr of age were studied using the same method, employing a methacholine inhalation challenge with transcutaneous oxygen pressure (tcPO2) monitoring. Three hundred and thirty-nine asthmatic subjects (male:female = 200:139, aged [mean +/- SEM] 7.2 +/- 0.2 yr) and 107 age-matched controls (male:female = 55:52, aged 5.3 +/- 0.3 yr) were enrolled in this study. TcPO2 was measured by a tcPO2 monitor, and subsequent doses of methacholine were then doubled until a 10% decrease in tcPO2 from its baseline value was reached. The cumulative dose of methacholine at the inflection point of tcPO2 (Dmin-PO2) was considered to represent the BRm. For the sake of comparison, respiratory resistance (Rr) in subjects more than 6 yr old was measured by the oscillation technique during methacholine inhalation challenge, and the threshold point of Rr (Dmin-Rr) was also considered to represent the BRm. In the asthmatic children aged 2 to 7 yr, Dmin-PO2 decreased significantly from 12.2 +/- 2.1 to 3.1 +/- 0.8 units, but after age 8 yr the values gradually increased from 3.1 +/- 0.7 to 6.4 +/- 1.6 units. In children aged 6 to 13 yr, Dmin-Rr showed the same increase as Dmin-PO2, from 2.0 +/- 0.5 to 5.8 +/- 1.4 units. These age-related changes in BRm reflected in both Dmin-PO2 and Dmin-Rr were also seen in the age-matched controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Phase I Evaluation of Telatinib, a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Combination with Irinotecan and Capecitabine in Patients with Advanced Solid Tumors
Authors: Marlies H.G. Langenberg, Petronella O. Witteveen, Jeanine M. Roodhart, Henk M.W. Verheul, Marja Mergui-Roelvink, Jana van der Sar, Erich Brendel, Nicole Laferriere, Jan H.M. Schellens, Emile E. Voest
Journal: Clinical Cancer Research (2010)

We studied the safety and tolerability of telatinib, an orally available, small-molecule tyrosine kinase inhibitor of the vascular endothelial growth factor receptor (VEGFR-2/VEGFR-3), platelet-derived growth factor receptor beta, and c-Kit in combination with capecitabine and irinotecan.Telatinib twice daily continuously, irinotecan once every 3 weeks, and capecitabine oral twice daily on day 1 to 14 were administered in cycles of 21 days in escalating doses in successive cohorts. Toxicity was evaluated to conform to the Common Terminology Criteria for Adverse Events version 3.0. Pharmacokinetic and (circulating) endothelial (progenitor) cell measurements were done. Tumor efficacy was evaluated using the Response Evaluation Criteria in Solid Tumors.Twenty-three patients were included in this phase I trial. Most frequently (>25%) reported adverse events of any grade were vomiting, nausea, fatigue, diarrhea, alopecia, and hand-foot syndrome. A silent myocardial infarction and two cases of decreased left ventricular ejection fraction were reported; both were reversible. Cardiac monitoring of the subsequent patients did not reveal other abnormalities. The study was terminated when the recommended single agent phase II doses of telatinib (900 mg twice daily) and capecitabine/irinotecan was reached. Pharmacokinetic profiles showed no clinically relevant changes upon coadministration of the three drugs. (Circulating) endothelial (progenitor) cell levels stabilized during treatment. Five of 23 patients had partial remission and 9 of 23 patients showed stable disease.Continuous administration of 900 mg telatinib twice daily can be safely combined with irinotecan (180 mg/m(2)) and capecitabine (1,000 mg/m(2) twice daily, day 1-14) and is the recommended schedule for further phase II studies. Tumor shrinkage and disease stabilization was observed. Cardiac toxicity needs further investigation in following studies.
Bioreducible alginate-poly(ethylenimine) nanogels as an antigen-delivery system robustly enhance vaccine-elicited humoral and cellular immune responses
Authors: Ping Li, Zichao Luo, Peng Liu, Ningning Gao, Yijuan Zhang, Hong Pan, Lanlan Liu, Ce Wang, Lintao Cai, Yifan Ma
Journal: Journal of Controlled Release (2013)
238 High frequency of single nucleotide polymorphisms (SNPS) at the human UGT1A gene locus: differential alterations of glucuronidation of two novel SNPS of the hepatic UGT1A4 gene
Authors: U EHMER, A VOGEL, A BARUT, B BLEIDISTEL, M MANNS, C STRASSBURG
Journal: Hepatology (2003)
A Susceptibility Gene Set for Early Onset Colorectal Cancer That Integrates Diverse Signaling Pathways: Implication for Tumorigenesis
Authors: Yi Hong, Kok Sun Ho, Kong Weng Eu, Peh Yean Cheah
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The causative genes for autosomal dominantly inherited familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer have been well characterized. There is, however, another 10% to 15% of early onset colorectal cancers (CRC) in which the genetic components are unclear. In this study, we used microarray technology to systematically search for differentially expressed genes in early onset CRC. Experimental Design: Young patients with non–FAP or non–hereditary nonpolyposis colorectal cancer, and healthy controls were age- (≤50 years old), ethnicity- (Chinese), and tissue-matched. RNAs extracted from colonic mucosa specimens were analyzed using GeneChip U133-Plus 2.0 Array. Results: Seven genes, CYR61, UCHL1, FOS, FOS B, EGR1, VIP, and KRT24, were consistently up-regulated in the mucosa of all six patients compared with the mucosa from four healthy controls. The overexpression of these genes was independently validated with a testing set of six patients and six healthy controls. Principal component analysis clustered the healthy control specimens separately from the patient specimens. Real-time PCR quantification with SYBR-Green on nine other patient specimens not previously used in microarray assays confirmed the up-regulation of these seven genes. These genes function in a multitude of biological processes ranging from transcription, angiogenesis, adhesion, and inflammatory regulation to protein catabolism in various cellular compartments, from extracellular to the nucleus. They integrate known tumorigenesis (Wnt, PI3K, MAP kinase, hypoxia, G protein–coupled receptor), neurologic, insulin-signaling, and NFAT-immune pathways into an intricate biological network. Conclusions: The data suggest that the patient's mucosa is primed for tumorigenesis when cellular homeostasis is disrupted, and that the seven overexpressed genes could potentially predict early onset CRC.
Staircase in frog ventricular muscle. Its dependence on membrane excitation and extracellular ionic composition.
Authors: J M Chesnais, F Kavaler, T W Anderson, E Coraboeuf
Journal: Circulation Research (1978)

Staircase was studied in frog ventricle strip preparations where it was possible to alter extracellular ionic composition extremely rapidly in the diastolic interval between beats. Several findings strongly indicate that staircase in this tissue is a result of progressively increasing calcium influx per beat, rather than a beat-by-beat augmentation of an intracellular calcium pool which contributes to activation. After a steady state of force development, the very next beat could be graded, from approximately zero force to the steady state value attained during the staircase progression, by grading the calcium concentration of a new Ringer's solution switched to perfuse the muscle in the diastolic period immediately before that beat. Also, action potentials, elicited during the "quiescent" period in the virtual absence of contraction (in 0.025 mm calcium Ringer's solution), markedly increase force development and accelerate the staircase seen upon return to normal Ringer's solution. Staircase is augmented and accelerated by prior exposure of the muscle, during the quiescent period, to calcium-poor media and markedly suppressed by prior exposure to sodium-poor media. Tetrodotoxin, in a dose that markedly slows the action potential upstroke, has no effect on staircase. Finally, staircase is seen to occur during a train of depolarizations (by voltage clamp) to inside positive levels greater than the equilibrium potential for sodium. It is concluded that changes in intracellular sodium concentration will alter the staircase response and may contribute to its genesis, but that this cannot be the sole cause of staircase.
Von Recklinghausen Neurofibromatosis
Authors: Vincent M. Riccardi
Journal: New England Journal of Medicine (1981)

Neurofibromatosis is of great importance not only to the thousands of affected patients and their physicians but also to researchers concerned with genetics, melanin synthesis, neural-crest embryology, cell-cell interactions, cancer, and other disciplines. However, only recently has neurofibromatosis been the subject of widespread, systematic studies of its nature and pathogenesis.1 Neurofibromatosis is a relatively common autosomal dominant trait2 with a frequency of about 1 in 3000; it is inexorably progressive, but with markedly variable expressivity. Although its commonness and wide range of expression may provide impetus for study, they are also the bane of any scientific approach to the disease. . . .