tbuckley/cabot-search huggingface dataset:
Plasma steroid levels after intra-articular injection of prednisolone acetate in patients with rheumatoid arthritis.
Authors: J S Reeback, J Chakraborty, J English, T Gibson, V Marks
Journal: Annals of the Rheumatic Diseases (1980)

Eight patients with rheumatoid arthritis received an intra-articular injection of either 50 mg or 100 mg of prednisolone acetate into the knee joint. After the injection plasma levels of prednisolone were measured by radioimmunoassay and plasma cortisol levels were estimated fluorimetrically. Peak prednisolone levels were reached at between 2 and 4 hours after the intra-articular injection at both dosage levels, though the peak was higher with the larger dose. The 50 mg dose did not have any effect on the plasma cortisol level at 24 or 48 hours, but there was some suppression of plasma cortisol levels for up to 48 hours after the 100 mg dose.
Mini-Boards: A Means of Evaluating Psychiatric Residents
Authors: DAVID E. RASKIN
Journal: American Journal of Psychiatry (1972)

The evaluation of general psychiatric skills is a different process from the evaluation of psychotherapeutic skills. Mini-boards, similar in format to the certification procedure of the American Board of Psychiatry and Neurology, test the resident's skill in interviewing a patient as well as his competence in general clinical and other basic areas. The miniboards, or a similar test, are recommended both to evaluate a psychiatric resident's progress and to better prepare him for the certification examination.
Systemic effects of salbutamol and salmeterol in patients with asthma.
Authors: J A Bennett, E T Smyth, I D Pavord, P J Wilding, A E Tattersfield
Journal: Thorax (1994)

Knowing the extent of the systemic effects of a new beta 2 agonist relative to an established drug is important for the prediction and interpretation of side effects. A recent study in which the effect of cumulative doses of salbutamol was compared with single doses of salmetreol suggested that, weight for weight, salmeterol may be up to 10 times more potent than salbutamol. This current study was designed to investigate further the dose equivalence of salmeterol and salbutamol.Twelve patients with mild asthma inhaled cumulative doses of placebo, salmeterol 25, 50, 100, and 200 micrograms, and salbutamol 100, 500, 1000, and 1000 micrograms on separate days at hourly intervals in a randomised double blind crossover study. Changes in forced expiratory volume in one second (FEV1), heart rate, plasma potassium concentration, systolic and diastolic blood pressure were measured. Dose equivalence was determined as the dose ratio of salmeterol to salbutamol for the 50% maximum response to salbutamol.No important changes occurred in any measurements following placebo. Salmeterol and salbutamol caused a near maximum increase in FEV1 following the first dose so the dose equivalence for the airway effects could not be estimated. Heart rate increased and plasma potassium concentration and diastolic blood pressure decreased in a dose dependent manner following salmeterol and salbutamol, with median dose equivalences for salmeterol compared with salbutamol of 17.7, 7.8, and 7.6, respectively.These results confirm that the systemic activity of salmeterol compared with salbutamol is higher than would be expected from in vitro data, particularly for heart rate. Whether this is because of the relatively high dose of salmeterol used or pharmacokinetic differences between the two drugs is uncertain.
Engineering of Bacteria for the Visualization of Targeted Delivery of a Cytolytic Anticancer Agent
Authors: Sheng-Nan Jiang, Seung-Hwan Park, Hee Jung Lee, Jin Hai Zheng, Hyung-Seok Kim, Hee-Seung Bom, Yeongjin Hong, Michael Szardenings, Myung Geun Shin, Sun-Chang Kim, Vasilis Ntziachristos, Hyon E Choy, Jung-Joon Min
Journal: Molecular Therapy (2013)

A number of recent reports have demonstrated that attenuated Salmonella typhimurium are capable of targeting both primary and metastatic tumors. The use of bacteria as a vehicle for the delivery of anticancer drugs requires a mechanism that precisely regulates and visualizes gene expression to ensure the appropriate timing and location of drug production. To integrate these functions into bacteria, we used a repressor-regulated tetracycline efflux system, in which the expression of a therapeutic gene and an imaging reporter gene were controlled by divergent promoters (tetAP and tetRP) in response to extracellular tetracycline. Attenuated S. typhimurium was transformed with the expression plasmids encoding cytolysin A, a therapeutic gene, and renilla luciferase variant 8, an imaging reporter gene, and administered intravenously to tumor-bearing mice. The engineered Salmonella successfully localized to tumor tissue and gene expression was dependent on the concentration of inducer, indicating the feasibility of peripheral control of bacterial gene expression. The bioluminescence signal permitted the localization of gene expression from the bacteria. The engineered bacteria significantly suppressed both primary and metastatic tumors and prolonged survival in mice. Therefore, engineered bacteria that carry a therapeutic and an imaging reporter gene for targeted anticancer therapy can be designed as a theranostic agent.
Calcium-Mediated Dual-Mode Regulation of Cardiac Sodium Channel Gating
Authors: Subrata Biswas, Deborah DiSilvestre, Yanli Tian, Victoria L. Halperin, Gordon F. Tomaselli
Journal: Circulation Research (2009)

Intracellular Ca(2+) ([Ca(2+)](i)) can trigger dual-mode regulation of the voltage gated cardiac sodium channel (Na(V)1.5). The channel components of the Ca(2+) regulatory system are the calmodulin (CaM)-binding IQ motif and the Ca(2+) sensing EF hand-like (EFL) motif in the carboxyl terminus of the channel. Mutations in either motif have been associated with arrhythmogenic changes in expressed Na(V)1.5 currents. Increases in [Ca(2+)](i) shift the steady-state inactivation of Na(V)1.5 in the depolarizing direction and slow entry into inactivated states. Mutation of the EFL (Na(V)1.5(4X)) shifts inactivation in the hyperpolarizing direction compared with the wild-type channel and eliminates the Ca(2+) sensitivity of inactivation gating. Modulation of the steady-state availability of Na(V)1.5 by [Ca(2+)](i) is more pronounced after the truncation of the carboxyl terminus proximal to the IQ motif (Na(V)1.5(Delta1885)), which retains the EFL. Mutating the EFL (Na(V)1.5(4X)) unmasks CaM-mediated regulation of the kinetics and voltage dependence of inactivation. This latent CaM modulation of inactivation is eliminated by mutation of the IQ motif (Na(V)1.5(4X-IQ/AA)). The LQT3 EFL mutant channel Na(V)1.5(D1790G) exhibits Ca(2+) insensitivity and unmasking of CaM regulation of inactivation gating. The enhanced effect of CaM on Na(V)1.5(4X) gating is associated with significantly greater fluorescence resonance energy transfer between enhanced cyan fluorescent protein-CaM and Na(V)1.5(4X) channels than is observed with wild-type Na(V)1.5. Unlike other isoforms of the Na channel, the IQ-CaM interaction in the carboxyl terminus of Na(V)1.5 is latent under physiological conditions but may become manifest in the presence of disease causing mutations in the CT of Na(V)1.5 (particularly in the EFL), contributing to the production of potentially lethal ventricular arrhythmias.
Morning-after pills.
Authors: S Rowlands
Journal: BMJ (1982)

Postcoital contraception has been in use in many countries for more than a decade, but some doctors still shrink from intervention in the reproductive process after ovulation--even when the timing is clearly before implantation. Around 80% of women who need postcoital treatment opt for hormone pills. The others have an intrauterine contraceptive device fitted. To be effective, hormonal treatment should be started within 72 hours of unprotected intercourse; thereafter the failure rate rises substantially above the 1% claimed. High doses of estrogen have been used, given for 5 days. More recently an estrogen-progestogen regimen has been devised in which the combination is taken in 2 doses 12 hours apart. The possibility that administration of an estrogen-progestogen combination just before implantation could be teratogenic has probably made clinicians overcautious. The circumstances in which insertion of an IUD is the preferred method include contraindications to the pill, the woman's choice of an IUD for future contraception, and instances where hormones are less effective. Up to the present, hormone treatment has been prescribed by doctors only after counselling and examination. Totally unsupervised administration of hormones should not be encouraged or condoned.
IL-1 family nomenclature
Authors: Charles Dinarello, William Arend, John Sims, Dirk Smith, Hal Blumberg, Luke O'Neill, Raphaela Goldbach-Mansky, Theresa Pizarro, H Hoffman, Philip Bufler, Marcel Nold, Pietro Ghezzi, Alberto Mantovani, Cecilia Garlanda, Diana Boraschi, Anna Rubartelli, Mihai Netea, Jos van der Meer, Leo Joosten, Tom Mandrup-Poulsen, Marc Donath, Eli Lewis, Josef Pfeilschifter, Michael Martin, Michael Kracht, H Muehl, Daniela Novick, Miodrag Lukic, Bruno Conti, Alan Solinger, Peyman Kelk, Frank van de Veerdonk, Chiristopher Gabel
Journal: Nature Immunology (2010)
Cardiovascular responses to PGI2 (prostacyclin) in the dog.
Authors: T M Fitzpatrick, I Alter, E J Corey, P W Ramwell, J C Rose, P A Kot
Journal: Circulation Research (1978)

Arachidonic acid (AA) produces characteristic hemodynamic changes in the canine circulation. These responses are blocked by prostaglandin (PG) synthetase inhibitors, indicating that AA and its nonprostanoic metabolites are not vasoactive. The hemodynamic effects of the cyclic endoperoxides, thromboxanes, and PGD2, PG2, and PGF2a differ from those produced by AA. PGI2, a newly identified product of AA, is reported to relax arterial strips. However, its cardiac and systemic effects are unknown. In 12 open-chest, anesthetized dogs, PGI2 (0.25-5.0 microgram/kg) produced a dose-related decrease in systemic arterial pressure (BP) and myocardial contractile force (MCF). In five left ventricular bypass preparations, PGI2 produced only a slight decrease in MCF at all doses, whereas the BP decreases were parallel to those in the intact preparation. AA, PGD2, PGE2, and PGI2 were administered in random order by bolus intravenous injections in approximately equidepressor doses to intact dogs. BP fell with each agent (AA, 300 microgram/kg, -25 percent; PGD2, 5 microgram/kg, -26 percent; PGE2, 5 microgram/kg, -26 percent PGI2, 0.5 microgram/kg, -26 percent). The vasodepressor action of PGI2 was approximately 10 times greater than that of PGD2 and PGE2. Pulmonary arterial pressure (PAP) rose significantly with PGD2 and PGE2 (AA, -1 percent; PGD2 +66 percent; PGE2, +20 percent; PGI2, -1 percent). Only PGE2 had a significant effect on MCF (AA, +7 percent; PGD2, +5 percent, PGE2, +20 percent; PGI2, -0.3). At this dose, PGI2 resembles AA in that it has little effect on either PAP or MCF. Of all known AA metabolites the response to PGI2 most closely resembles that of exogenous AA in the dog.
Evaluation of a New, Rapid, and Quantitative D-Dimer Test in Patients with Suspected Pulmonary Embolism
Authors: EMMANUEL OGER, CHRISTOPHE LEROYER, LUC BRESSOLLETTE, MICHEL NONENT, EMMANUELLE LE MOIGNE, YVES BIZAIS, JEAN AMIRAL, MARC GRIMAUX, JEAN CLAVIER, PATRICK ILL, JEAN-FRANÇOIS ABGRALL, DOMINIQUE MOTTIER
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Previous studies have suggested the utility of D-Dimer ELISA assays in eliminating a diagnosis of pulmonary embolism (PE). Our objectives were to evaluate the performance of a new, rapid, quantitative, and automated Liatest D-Dimer Assay in patients with suspected PE. Three hundred eighty-six consecutive patients referred to our institution between March 1992 and December 1996 for clinically suspected PE, with recent clinical signs not exceeding 1 wk, were included in this study. Diagnosis of PE was based on clinical evaluation, radionuclide lung imaging, lower limb examination, and, when required, pulmonary angiography. D-Dimer performances, for both Liatest D-Dimer and standard D-Dimer ELISA (Asserachrom DDi), assays, were assessed at the end of the study. Among the 386 patients tested, 146 (37.8%) were classified as PE-positive. Liatest D-Dimer assay had a 100% sensitivity (95% confidence interval, 97 to 100%) and a negative predictive value of 100% (95% confidence interval, 94 to 100%). A normal result, below the cutoff of 500 ng/ml, occurred in 83 of the 386 (21%) patients. There was a strong agreement between Liatest D-Dimer and Asserachrom DDi analyses. These findings suggest that this rapid, quantitative, and automated D-Dimer assay provides a useful diagnostic tool for the clinician with regard to exclusion of PE.
Ventricular Arrhythmias in Patients Undergoing Noncardiac Surgery
Authors: Brian O'Kelly
Journal: JAMA (1992)

<h3>Objective.</h3> —To determine the incidence, clinical predictors and prognostic importance of perioperative ventricular arrhythmias. <h3>Design.</h3> —Prospective cohort study (Study of Perioperative Ischemia). <h3>Setting.</h3> —University-affiliated Department of Veterans Affairs Medical Center, San Francisco, Calif. <h3>Subjects.</h3> —A consecutive sample of 230 male patients, with known coronary artery disease (46%) or at high risk of coronary artery disease (54%), undergoing major noncardiac surgical procedures. <h3>Measurements.</h3> —We recorded cardiac rhythm throughout the preoperative (mean=21 hours), intraoperative (mean=6 hours), and postoperative (mean=38 hours) periods using continuous ambulatory electrocardiographic monitoring. Adverse cardiac outcomes were noted by physicians blinded to information about arrhythmias. <h3>Main Results.</h3> —Frequent or major ventricular arrhythmias (&gt;30 ventricular ectopic beats per hour, ventricular tachycardia) occurred in 44% of our patients: 21% preoperatively, 16% intraoperatively, and 36% postoperatively. Compared with the preoperative baseline, the severity of arrhythmia increased in only 2% of patients intraoperatively but in 10% postoperatively. Preoperative ventricular arrhythmias were more common in smokers (odds ratio [OR], 4.1; 95% confidence interval [Cl], 1.2 to 15.0), those with a history of congestive heart failure (OR, 4.1; 95% Cl, 1.9 to 9.0), and those with electrocardiographic evidence of myocardial ischemia (OR, 2.2; 95% Cl, 1.1 to 4.7). Preoperative arrhythmias were associated with the occurrence of intraoperative and postoperative arrhythmias (OR, 7.3; 95% CI, 3.3 to 16.0, and OR, 6.4; 95% Cl, 2.7 to 15.0, respectively). Nonfatal myocardial infarction or cardiac death occurred in nine men; these outcomes were not significantly more frequent in those with prior perioperative arrhythmias, albeit with wide Cls (OR, 1.6; 95% CI, 0.4 to 6.2). <h3>Conclusion.</h3> —Almost half of all high-risk patients undergoing noncardiac surgery have frequent ventricular ectopic beats or nonsustained ventricular tachycardia. Our results suggest that these arrhythmias, when they occur without other signs or symptoms of myocardial infarction, may not require aggressive monitoring or treatment during the perioperative period. (<i>JAMA</i>. 1992;268:217-221)
LATENT VIRAL INFECTION OF CELLS IN TISSUE CULTURE
Authors: Herbert R. Morgan, John P. Bader
Journal: The Journal of Experimental Medicine (1957)

By maintaining L cells in a balanced salt solution of inorganic salts and glucose (BSS) for 2 days or more, they are rendered incapable of supporting the growth of psittacosis virus (6BC), though it infects such cells and is present intracellularly for as long as 3 days in a non-infectious phase. The addition of an enriched medium to such a culture of cells at any time up to 4 days after infection results in the appearance of infectious virus within these cells, which multiplies and is released from the cells, providing the entire period of exposure of such cells to the BSS does not exceed 6 days, following which the cells die. A latent infection with psittacosis virus in a non-infectious phase has been established in a pure line of cells which possess properties of malignancy.
The antimicrobial peptide cathelicidin modulates<i>Clostridium difficile</i>-associated colitis and toxin A-mediated enteritis in mice
Authors: Tressia C Hing, Samantha Ho, David Q Shih, Ryan Ichikawa, Michelle Cheng, Jeremy Chen, Xinhua Chen, Ivy Law, Robert Najarian, Ciaran P Kelly, Richard L Gallo, Stephan R Targan, Charalabos Pothoulakis, Hon Wai Koon
Journal: Gut (2012)

<h3>Background</h3> <i>Clostridium</i><i>difficile</i> mediates intestinal inflammation by releasing toxin A (TxA), a potent enterotoxin. Cathelicidins (<i>Camp</i> as gene name, LL-37 peptide in humans and mCRAMP peptide in mice) are antibacterial peptides that also posses anti-inflammatory properties. <h3>Objectives</h3> To determine the role of cathelicidins in models of <i>Clostridium difficile</i> infection and TxA-mediated ileal inflammation and cultured human primary monocytes. <h3>Design</h3> Wild-type (WT) and mCRAMP-deficient (<i>Camp</i><sup>−/−</sup>) mice were treated with an antibiotic mixture and infected orally with <i>C difficile</i>. Some mice were intracolonically given mCRAMP daily for 3 days. Ileal loops were also prepared in WT mice and treated with either saline or TxA and incubated for 4 h, while some TxA-treated loops were injected with mCRAMP. <h3>Results</h3> Intracolonic mCRAMP administration to <i>C difficile</i>-infected WT mice showed significantly reduced colonic histology damage, apoptosis, tissue myeloperoxidase (MPO) and tumour necrosis factor (TNF)α levels. Ileal mCRAMP treatment also significantly reduced histology damage, tissue apoptosis, MPO and TNFα levels in TxA-exposed ileal loops. WT and <i>Camp</i><sup>−/−</sup> mice exhibited similar intestinal responses in both models, implying that <i>C difficile</i>/TxA-induced endogenous cathelicidin may be insufficient to modulate <i>C difficile</i>/TxA-mediated intestinal inflammation. Both LL-37 and mCRAMP also significantly reduced TxA-induced TNFα secretion via inhibition of NF-κB phosphorylation. Endogenous cathelicidin failed to control <i>C difficile</i> and/or toxin A-mediated inflammation and even intestinal cathelicidin expression was increased in humans and mice. <h3>Conclusion</h3> Exogenous cathelicidin modulates <i>C difficile</i> colitis by inhibiting TxA-associated intestinal inflammation. Cathelicidin administration may be a new anti-inflammatory treatment for <i>C difficile</i> toxin-associated disease.
Hormone replacement therapy and risk of hip fracture: population based case-control study
Authors: K. Michaelsson, J. A Baron, B. Y Farahmand, O. Johnell, C. Magnusson, P.-G. Persson, I. Persson, S. Ljunghall
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. <b>Design:</b> Population based case-control study. <b>Setting:</b> Six counties in Sweden. <b>Subjects:</b> 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. <b>Main outcome measure:</b> Use of hormone replacement therapy. <b>Results:</b> Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. <b>Conclusions:</b> Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen. <h3>Key messages</h3> Hormone replacement therapy should be continued for long periods for optimal protection of hip fracture No overall substantial hip fracture protection remains after five years without hormone replacement therapy Therapy can be initiated several years after menopause without loss of fracture protection Oral or transdermal therapy are equally effective in reducing the risk of hip fracture The addition of progestins permits lower doses of oestrogens
Hypercholesterolemia in Minipigs Impairs Left Ventricular Response to Stress
Authors: Gregor Theilmeier, Peter Verhamme, Steven Dymarkowski, Heike Beck, Hilde Bernar, Marleen Lox, Stefan Janssens, Marie-Christine Herregods, Erik Verbeken, Désiré Collen, Karl Plate, Willem Flameng, Paul Holvoet
Journal: Circulation (2002)

Background— Hypercholesterolemia induces functional and structural changes of the microvasculature and reduces coronary flow reserve in humans and experimental animals. The effect of hypercholesterolemia on left ventricular (LV) function in the absence of coronary stenosis is, however, unknown. Our objective was therefore to assess the effect of hypercholesterolemia and cholesterol withdrawal on LV function in the presence of advanced coronary plaques that do not cause stenosis. Methods and Results— Twenty-eight minipigs on cholesterol diet for 34 weeks and 16 control pigs were studied. Seven hypercholesterolemic pigs were withdrawn from the diet for 26 weeks. LV function was assessed with cine-MRI, myocardial blood flow with colored microspheres, and capillary density with immunohistochemistry, and microvascular endothelial cell apoptosis with terminal dUTP nick-end labeling staining. Hypercholesterolemia (17±8 versus 268±150 versus 12±10 mg/dL LDL cholesterol, control versus hypercholesterolemic versus cholesterol withdrawal; P &lt;0.001) induced atherosclerosis but not stenosis in the left coronary artery. Baseline cardiac output, ejection fraction, and stroke volume were similar in control and hypercholesterolemic pigs. In dobutamine stress test, cardiac output ( P &lt;0.05) and stroke volume ( P &lt;0.01) were lower in hypercholesterolemic pigs compared with controls. The impaired response to dobutamine was reversible by dietary cholesterol withdrawal. Hypercholesterolemia reduced endomyocardial coronary flow reserve ( P &lt;0.01) and capillary density ( P &lt;0.05) and induced capillary endothelial cell apoptosis. Hypercholesterolemic pigs failed to reduce vascular resistance in response to increased LV workload and pharmacological vasodilation. Conclusion— LDL hypercholesterolemia in minipigs impaired LV response to dobutamine stress in the absence of coronary stenosis.