tbuckley/cabot-search huggingface dataset:
Effect of Butorphanol Tartrate on Shock-Related Discomfort During Internal Atrial Defibrillation
Authors: Carl Timmermans, Luz-Maria Rodriguez, Gregory M. Ayers, Hendrik Lambert, Joep L. R. M. Smeets, Johan W. S. Vlaeyen, Adelin Albert, Hein J. J. Wellens
Journal: Circulation (1999)

Background —In patients with atrial fibrillation, intracardiac atrial defibrillation causes discomfort. An easily applicable, short-acting analgesic and anxiolytic drug would increase acceptability of this new treatment mode. Methods and Results —In a double-blind, placebo-controlled manner, the effect of intranasal butorphanol, an opioid, was evaluated in 47 patients with the use of a step-up internal atrial defibrillation protocol (stage I). On request, additional butorphanol was administered and the step-up protocol continued (stage II). Thereafter, if necessary, patients were intravenously sedated (stage III). After each shock, the McGill Pain Questionnaire was used to obtain a sensory (S), affective (A), evaluative (E), and total (T) pain rating index (PRI) and a visual analogue scale analyzing pain (VAS-P) and fear (VAS-F). For every patient, the slope of each pain or fear parameter against the shock number was calculated and individual slopes were averaged for the placebo and butorphanol group. All patients were cardioverted at a mean threshold of 4.4±3.3 J. Comparing both patient groups for stage II, the mean slopes for PRI-T ( P =0.0099), PRI-S ( P =0.019), and PRI-E ( P =0.015) became significantly lower in the butorphanol group than in the placebo group. Comparing patients who received the same shock intensity ending stage I and going to stage II, in those patients randomized to placebo the mean VAS-P ( P =0.023), PRI-T ( P =0.029), PRI-S ( P =0.030), and PRI-E ( P =0.023) became significantly lower after butorphanol administration. Conclusions —During a step-up internal atrial defibrillation protocol, intranasal butorphanol decreased or stabilized the value of several pain variables and did not affect fear. Of the 3 qualitative components of pain, only the affective component was not influenced by butorphanol. The PRI evaluated pain more accurately than the VAS.
Effect of once-daily atenolol on ambulatory blood pressure.
Authors: M W Craig, D Kenny, S Mann, V Balasubramanian, E B Raftery
Journal: BMJ (1979)

Treatment of mastalgia with bromocriptine: a double-blind cross-over study Mastalgia is often associated with fibrocystic disease of the breast.Treatments, however, often fail, probably owing to an unsatisfactory understanding of the nature of the condition.In this study we assess the therapeutic efficacy of bromocriptine. Patients, methods, and resultsSevere mastalgia was the dominant feature in 10 women with diffuse fibrocystic disease of the breast as judged by palpation and mammography and verified histologically.One patient (case 1) had galactorrhoea.None had prominent characteristics of the premenstrual syndrome.Mastalgia had been present for from six months to several years.In a double-blind cross- over trial patients were allocated at random to receive either bromocriptine or identical placebo capsules, each for a period of two months, in a dose of one capsule (bromocriptine 2-5 mg or placebo) daily during the first week of each period and thereafter two capsules daily.For one month before the trial and throughout the period of medication the presence and intensity of pain were recorded daily by each patient.They were seen in the outpatient clinic every four weeks.The code was broken at the end of each trial.Serum prolactin concentration was measured before the trial, on the day of cross- over, and on the final day of the trial (normal range 3-0-13-5 jug/l).During treatment with bromocriptine pain was totally or almost totally relieved in eight patients and in two the pain was much reduced (table).Placebo treatment failed to relieve mastalgia in any patient except one (case 9), in whom the relief during bromocriptine continued while taking placebo.Statistical analysis by Koch's method' showed that the relief obtained during bromocriptine therapy was significantly greater (P<002) than that during placebo medication, while period effects as well as carry-over effects were absent (P > 0-05).Mastalgia reappeared as soon as active medication was stopped, with the exception of the patient in case 9.The breasts became smaller, softer, and less tender during bromocriptine treatment.The pretrial serum prolactin concentration was slightly raised in three patients and normal in seven.During treatment with bromocriptine these concentrations were significantly lowered (P<0-01, sign test).There were no side effects from placebo.While taking bromocriptine five patients had slight, transitory nausea and dizziness, which is a recognised side effect.Three others had persistent and more pronounced nausea, dizziness, and general malaise.
Differentiation of rat myocytes in single cell cultures with and without proliferating nonmyocardial cells. Cross-striations, ultrastructure, and chronotropic response to isoproterenol.
Authors: P Simpson, S Savion
Journal: Circulation Research (1982)

Proliferating nonmyocardial cells (NMCs) complicate primary heart cultures and may influence myocardial cell (MC) differentiation.In cultures from the day-old rat ventricle, we validated a method to arrest this proliferation; and we quantitated cross-striated cells and the chronotropic response to isoproterenol to assess MC differentiation.MCs were cultured at single cell density using an improved method.By 4 days, all cells could be identified as MCs or NMCs.In cultures treated for 3 days with bromodeoxyuridine (BrdU), 0.1 miw, serial cell counts were unchanged through 11 days.Among 50,000 cells from 110 cultures, 75-80% were MCs.In control cultures without BrdU, NMC density was 3-and 6-fold that in BrdU-treated cultures at days 5 and 8, respectively (P < 0.01), although the MCs were not overgrown.The MCs did not proliferate in either culture.The proportion of living MCs with cross-striations was similar in treated and control cultures at day 5 (72.6% vs. 69.9%,P > 0.05) but was lower in controls at day 8 (86.3% vs. 50.4%,P < 0.01).A sensitive (ED 50 10-100 pM), specific chronotropic response to L-isoproterenol was present in both treated and control cultures, but the maximum response was only 20-30% as great in controls on days 4 and 8 (P < 0.01).Baseline beating rates were the same.The MCs had well-differentiated ultrastructure, including a T system.By autoradiography, a maximum 18.4% of MCs had nuclear incorporation of 3 H-BrdU at day 8. Media conditioned by NMCs or by the control cultures did not change the cross-striations or isoproterenol response of BrdU-treated cultures.Thus, in a new culture preparation with few and stable NMCs, morphological and functional MC characteristics were different from those of MCs in cultures with proliferating NMCs.We suggest that an MC-NMC interaction can alter MC properties and that this effect should be considered in studies of primary rat heart cultures.The pure, stable, well-differentiated MCs in BrdUtreated cultures will be useful for studying MC growth, repair, and other time-dependent phenomena.CircRes 50: [101][102][103][104][105][106][107][108][109][110][111][112][113][114][115][116] 1982 PRIMARY cultures of cells from the hearts of neonatal rats and embryonic chicks are used by many investigators.(See reviews by Lieberman and Sano, 1976;Sperelakis, 1978; Auclair and Freyss-Beguin, 1980).A major, unresolved problem with these cultures is contamination by a population of rapidly proliferating nonmyocardial cells (NMCs), the precise identity of which is unclear (Balk, 1980).The initial proportion of these contaminating cells can be reduced by the differential attachment technique (Hyde et al., 1969); but they eventually overgrow the myocardial cells (MCs), which are said to divide much more slowly (Kasten, 1972).This progressive increase in cell number is not charac-
Deficiencies of GM-CSF and Interferon γ Link Inflammation and Cancer
Authors: Thomas Enzler, Silke Gillessen, John P. Manis, David Ferguson, James Fleming, Frederick W. Alt, Martin Mihm, Glenn Dranoff
Journal: The Journal of Experimental Medicine (2003)

Chronic inflammation contributes to carcinogenesis, but the underlying mechanisms are poorly understood. We report that aged granulocyte-macrophage colony stimulating factor (GM-CSF)-deficient mice develop a systemic lupus erythematosis (SLE)-like disorder associated with the impaired phagocytosis of apoptotic cells. Concurrent deficiency of interferon (IFN)-γ attenuates the SLE, but promotes the formation of diverse hematologic and solid neoplasms within a background of persistent infection and inflammation. Whereas activated B cells show a resistance to fas-induced apoptosis, antimicrobial therapy prevents lymphomagenesis and solid tumor development. These findings demonstrate that the interplay of infectious agents with cytokine-mediated regulation of immune homeostasis is a critical determinant of cancer susceptibility.
Kupffer cell activation and portal hypertension
Authors: C. J. Steib
Journal: Gut (2011)

<h3>Introduction</h3> Stent-assisted coil embolization of cerebral aneurysms can be performed using one of multiple techniques. Jailing is the ability to trap microcatheter in the aneurysm while laying a stent across the neck of the aneurysm followed by coiling the aneurysm. Crossing technique refers to placing a microcatheter through the interstices of the stent and then into the aneurysm in order to treat it. Neuroform Atlas stent can be delivered via a 0.0165 inch inner diameter microcatheter which would allow for easier placement of two microcatheters simultaneously and hence a more efficient trapping technique. <h3>Method</h3> Over 298 patients were treated in multiple centers with Neuroform Atlas Stent-assisted coiling of aneurysms. The treating physicians decided on the technique of treatment including jailing, crossing, or others (jailing followed by re-crossing, stenting followed by re-crossing at a different time, or unknown). Patients’ demographics, shape, dimension, and location of the aneurysm, as well as the number of coils and procedure duration were analyzed ad hoc. Intra-procedure complications of the different techniques were also recorded. In addition, a 12-month follow up angiogram (248/298) was performed, and Raymond score was evaluated by core laboratory. <h3>Results</h3> Similar characteristics were observed between the two groups (jailing and re-crossing) in the shape, dimensions, and location of the aneurysms. There was also no increase in the number of coils used or duration of the procedure between the two different techniques. Procedures related adverse events and device related adverse events were similar between the 2 groups. A higher proportion of complete occlusion and a lower proportion of residual aneurysm (2.7%) were observed in the jailing group, compared with the re-cross group (7.3%). However, the difference is not statistically significant. <h3>Conclusion</h3> Jailing technique might present an alternative to re-crossing the Neuroform Atlas Stent without a significant increase in complications and it may decrease the chance of aneurysm recurrence at 12 months. <h3>Disclosures</h3> <b>A. Khaldi:</b> None. <b>P. Williams:</b> None. <b>A. Jadhav:</b> None. <b>R. Hanel:</b> 1; C; Medtonic, Stryker, Cerenovus, Microvention. 2; C; Stryker, Medtronic, Cerenovus, Microvention. 4; C; Neurvana, Elum, EndoStream, Three Rivers Medical Inc, Cerebrotech, In NeuroCO.. 6; C; Scientific Advisor, MIVI, Scientific Advisor, Elum, Scientific Advisor, Three Rivers Medical. <b>D. Frei:</b> 2; C; Stryker, Siemens. 3; C; Stryker, Penumbra, Philips, Genetech, Siemens, VIZ AI. 6; C; Medical Advisor for Memory Medical. <b>S. Hetts:</b> 2; C; Microvention. 6; C; Core Lab services for Stryker and Micro Vention Terumo. <b>O. Zaidat:</b> 1; C; Stryker, Medtronic, Cerenovus, Penumbra, Genetech. 2; C; Cerenovus, Stryker, Penumbra, Medtronic. 6; C; Ownership in Galaxy Therapeutics LLC, Endovascular Committee co chair of NIH StrokeNet Consortium. <b>B. Jankowitz:</b> 2; C; Stryker, Medtronic.
Molecular basis of cardiac troponin T isoform heterogeneity in rabbit heart.
Authors: A Greig, Y Hirschberg, P A Anderson, C Hainsworth, N N Malouf, A E Oakeley, B K Kay
Journal: Circulation Research (1994)

In the rabbit heart, multiple isoforms of cardiac troponin T (cTnT1 through cTnT5, from largest in size to smallest), a protein essential for calcium-regulated myofibrillar ATPase activity, have been identified, and a correlation has been found between these isoforms and myofilament sensitivity to calcium. We have sought to establish the molecular basis of this diversity. Restriction-digest analysis of genomic DNA has indicated that the rabbit cTnT gene is a single-copy gene. cTnT cDNA clones were isolated from cDNA libraries, yielding a consensus sequence for the protein. Newborn rabbit heart cDNAs, obtained using the reverse-transcriptase polymerase chain reaction (RT-PCR), were amplified using primers derived from this cDNA. Three full-length cDNAs that differed by the inclusion or exclusion of three short nucleotide sequences within the cDNAs were obtained. Amplification in the 5' half of the cDNAs confirmed that multiple cTnT products arose because of the variable inclusion of an 18- and a 30-nt sequence. The 30-nt sequence has homology with previously described alternatively spliced exons in rat and chicken cTnT, whereas the 18-nt sequence has not been described previously. RT-PCR in the 3' half of the cDNAs confirmed an additional region of heterogeneity: the presence, in part or in full, or absence of a 9-nt region, which matches the alternatively spliced exon 12 described for rat cTnT. In vitro transcription and translation of four cDNA clones containing both the 18- and 30-nt sequences, the 30-nt sequence, the 18-nt sequence, or neither generated protein isoforms that comigrated with cTnT1, cTnT2, cTnT3, and cTnT4, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
STUDIES ON ANTIBODY PRODUCTION
Authors: Andre Cruchaud, Albert H. Coons
Journal: The Journal of Experimental Medicine (1964)

Young adult mice were primed with 20 Lf (56 microg) of diphtheria toxoid and given a second injection of the same size 40 days later. This procedure produces a reproducible secondary response which can be used as a standard. Chloramphenicol in maximum dosage prevents the unknown process by which the animal is primed for the second response. To be fully inhibitory, the drug must be given from the hour of the first antigen injection in maximum dosage for 2 weeks. A delay of 48 hours in starting the drug allows completion of the priming process, and shorter delays produce partial inhibition. Hence the initiation of priming is a rapid process sensitive to chloramphenicol. Subsequent changes in the cell population necessary for the full development of priming are not sensitive to chloramphenicol. The secondary antibody response is not inhibited in mice by chloramphenicol at the doses employed.
Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2
Authors: Jonathan Sitrin, Aaron Ring, K. Christopher Garcia, Christophe Benoist, Diane Mathis
Journal: The Journal of Experimental Medicine (2013)

Regulatory T (T reg) cells control progression to autoimmune diabetes in the BDC2.5/NOD mouse model by reining in natural killer (NK) cells that infiltrate the pancreatic islets, inhibiting both their proliferation and production of diabetogenic interferon-γ. In this study, we have explored the molecular mechanisms underlying this NK–T reg cell axis, following leads from a kinetic exploration of gene expression changes early after punctual perturbation of T reg cells in BDC2.5/NOD mice. Results from gene signature analyses, quantification of STAT5 phosphorylation levels, cytokine neutralization experiments, cytokine supplementation studies, and evaluations of intracellular cytokine levels collectively argue for a scenario in which T reg cells regulate NK cell functions by controlling the bioavailability of limiting amounts of IL-2 in the islets, generated mainly by infiltrating CD4+ T cells. This scenario represents a previously unappreciated intertwining of the innate and adaptive immune systems: CD4+ T cells priming NK cells to provoke a destructive T effector cell response. Our findings highlight the need to consider potential effects on NK cells when designing therapeutic strategies based on manipulation of IL-2 levels or targets.
Smoking may mimic effect of antidepressants
Authors: S. Gottlieb
Journal: BMJ (2001)

Cigarette smoking may have effects on the human brain similar to those of antidepressant drugs, and this may explain the high rate of smoking among depressed people and their resistance to quitting.

Researchers have noted previously that depressed people are more likely to smoke and are more resistant to quitting. However, it was unclear if nicotine or other chemicals taken in during smoking directly affected the brains of people who were depressed.

In a new study Dr Gregory Ordway, professor of …
Effectiveness of a Self-Management Intervention in Patients With Screen-Detected Type 2 Diabetes
Authors: Bart Thoolen, Denise De Ridder, Jozien Bensing, Cora Maas, Simon Griffin, Kees Gorter, Guy Rutten
Journal: Diabetes Care (2007)

To examine the effectiveness of a theory-driven self-management course in reducing cardiovascular risk in patients with screen-detected type 2 diabetes, taking ongoing medical treatment into account.A total of 196 screen-detected patients, receiving either intensive pharmacological or usual-care treatment since diagnosis (3-33 months previously), were subsequently randomized to a control or intervention condition (self-management course). A 2 x 2 factorial design evaluated the behavioral intervention (self-management course versus control) nested within the medical treatment (intensive versus usual-care), using multilevel regression modeling to analyze changes in patients' BMI, A1C, blood pressure (BP), and lipid profiles over 12 months, from the start of the 3-month course to 9-month follow-up.The self-management course significantly reduced BMI (-0.77 kg/m2) and systolic BP (-6.2 mmHg) up until the 9-month follow-up, regardless of medical treatment. However, intensive medical treatment was also independently associated with lower BP, A1C, total cholesterol, and LDL before the course and further improvements in systolic BP (-4.7 mmHg). Patients receiving both intensive medical treatment and the self-management course therefore had the best outcomes.This self-management course was effective in achieving sustained reductions in weight and BP, independent of medical treatment. A combination of behavioral and medical interventions is particularly effective in reducing cardiovascular risk in newly diagnosed patients.
Novel Strategies to Enforce an Epithelial Phenotype in Mesenchymal Cells
Authors: Ana-Maria Dragoi, Rachel Swiss, Beile Gao, Hervé Agaisse
Journal: Cancer Research (2014)

E-cadherin downregulation in cancer cells is associated with epithelial-to-mesenchymal transition (EMT) and metastatic prowess, but the underlying mechanisms are incompletely characterized. In this study, we probed E-cadherin expression at the plasma membrane as a functional assay to identify genes involved in E-cadherin downregulation. The assay was based on the E-cadherin-dependent invasion properties of the intracellular pathogen Listeria monocytogenes. On the basis of a functional readout, automated microscopy and computer-assisted image analysis were used to screen siRNAs targeting 7,000 human genes. The validity of the screen was supported by its definition of several known regulators of E-cadherin expression, including ZEB1, HDAC1, and MMP14. We identified three new regulators (FLASH, CASP7, and PCGF1), the silencing of which was sufficient to restore high levels of E-cadherin transcription. In addition, we identified two new regulators (FBXL5 and CAV2), the silencing of which was sufficient to increase E-cadherin expression at a posttranscriptional level. FLASH silencing regulated the expression of E-cadherin and other ZEB1-dependent genes, through posttranscriptional regulation of ZEB1, but it also regulated the expression of numerous ZEB1-independent genes with functions predicted to contribute to a restoration of the epithelial phenotype. Finally, we also report the identification of siRNA duplexes that potently restored the epithelial phenotype by mimicking the activity of known and putative microRNAs. Our findings suggest new ways to enforce epithelial phenotypes as a general strategy to treat cancer by blocking invasive and metastatic phenotypes associated with EMT.
Does This Patient Have a Hemorrhagic Stroke?
Authors: Shauna Runchey, Steven McGee
Journal: JAMA (2010)

The 2 fundamental subtypes of stroke are hemorrhagic stroke and ischemic stroke. Although neuroimaging is required to distinguish these subtypes, the diagnostic accuracy of bedside findings has not been systematically reviewed.To determine the accuracy of clinical examination in distinguishing hemorrhagic stroke from ischemic stroke.MEDLINE and EMBASE searches of English-language articles published from January 1966 to April 2010.Prospective studies of adult patients with stroke that compared initial clinical findings with accepted diagnostic standards of hemorrhagic stroke (computed tomography or autopsy).Both authors independently appraised study quality and extracted relevant data.Nineteen prospective studies meeting inclusion criteria were identified (N = 6438 patients; n = 1528 [24%] with hemorrhage stroke). Several findings significantly increase the probability of hemorrhagic stroke: coma (likelihood ratio [LR], 6.2; 95% confidence interval [CI], 3.2-12), neck stiffness (LR, 5.0; 95% CI, 1.9-12.8), seizures accompanying the neurologic deficit (LR, 4.7; 95% CI, 1.6-14), diastolic blood pressure greater than 110 mm Hg (LR, 4.3; 95% CI, 1.4-14), vomiting (LR, 3.0; 95% CI, 1.7-5.5), and headache (LR, 2.9; 95% CI, 1.7-4.8). Other findings decrease the probability of hemorrhage: cervical bruit (LR, 0.12; 95% CI, 0.03-0.47) and prior transient ischemic attack (LR, 0.34; 95% CI, 0.18-0.65). A Siriraj score greater than 1 increases the probability of hemorrhage (LR, 5.7; 95% CI, 4.4-7.4) while a score lower than -1 decreases the probability (LR, 0.29; 95% CI, 0.23-0.37). Nonetheless, many patients with stroke lack any diagnostic finding, and 20% have Siriraj scores between 1 and -1, which are diagnostically unhelpful (LR, 0.94; 95% CI, 0.77-1.1).In patients with acute stroke, certain findings accurately increase or decrease the probability of intracranial hemorrhage, but no finding or combination of findings is definitively diagnostic in all patients, and diagnostic certainty requires neuroimaging.