tbuckley/cabot-search huggingface dataset:
Comparison of Low-Molecular-Weight Heparin With Unfractionated Heparin Acutely and With Placebo for 6 Weeks in the Management of Unstable Coronary Artery Disease
Authors: Werner Klein, Arnd Buchwald, Stuart E. Hillis, Scott Monrad, Ginés Sanz, A. Graham G. Turpie, Jan van der Meer, Eric Olaisson, Sven Undeland, Karin Ludwig
Journal: Circulation (1997)

Background Low-molecular-weight heparin has a number of pharmacological and pharmacokinetic advantages over unfractionated heparin that make it potentially suitable, when used in combination with aspirin, for the treatment of unstable coronary artery disease. Method and Results Patients with unstable angina or non–Q-wave myocardial infarction (1482) were included in the study, which had two phases. In an open, acute phase (days 1 to 6), patients were assigned either twice-daily weight-adjusted subcutaneous injections of dalteparin (120 IU/kg) or dose-adjusted intravenous infusion of unfractionated heparin. In the double-blind, prolonged treatment phase (days 6 to 45), patients received subcutaneously either dalteparin (7500 IU once daily) or placebo. During the first 6 days, the rate of death, myocardial infarction, or recurrence of angina was 7.6% in the unfractionated heparin-treated patients and 9.3% in the dalteparin-treated patients (relative risk, 1.18; 95% confidence interval [CI], 0.84 to 1.66). The corresponding rates in the two treatment groups for the composite end point of death or myocardial infarction were 3.6% and 3.9%, respectively (relative risk, 1.07; 95% CI, 0.63 to 1.80). Revascularization procedures were undertaken in 5.3% and 4.8% of patients in unfractionated heparin and dalteparin groups, respectively (relative risk, 0.88; 95% CI, 0.57 to 1.35). Between days 6 and 45, the rate of death, myocardial infarction, or recurrence of angina was 12.3% in both the placebo and dalteparin groups (relative risk, 1.01; 95% CI, 0.74 to 1.38). The corresponding rates for death or myocardial infarction were 4.7% and 4.3% (relative risk, 0.92; 95% CI, 0.54 to 1.57). Revascularization procedures were undertaken in 14.2% and 14.3% of patients in the placebo and dalteparin groups, respectively. Conclusions Our results add to previous evidence suggesting that the low-molecular-weight heparin dalteparin administered by twice-daily subcutaneous injection may be an alternative to unfractionated heparin in the acute treatment of unstable angina or non–Q-wave myocardial infarction. Prolonged treatment with dalteparin at a lower once-daily dose in our study did not confer any additional benefit over aspirin (75 to 165 mg) alone.
Management of adult lower respiratory tract infection in primary care
Authors: K STEELE
Journal: Thorax (2001)

Acute lower respiratory tract infection (acute bronchitis) refers to the onset of productive cough in a patient with no history of chronic obstructive pulmonary disease and no evidence of pneumonia. The Fourth National Morbidity Survey (1991–2) from general practice claims that acute cough is the most common reason given for consulting a GP in the UK.1 Population based estimates of the incidence of acute bronchitis range from 33 to 45 cases/1000 per year.2 3 Descriptive epidemiology of common symptoms and their natural history and outcome is an area which the MRC highlights as a priority for primary care research.4 In this issue of Thorax Macfarlane et al report a large prospective case series detailing the incidence, aetiology, management, and outcome of previously well adults presenting to their general practitioner with symptoms of acute lower respiratory tract infection.5 They found there was no relationship between the doctor's initial clinical assessment that the patient had an infection warranting antibiotics and the outcome or with subsequent laboratory confirmation of a bacterial/atypical infection.

Quantitative systematic reviews of randomised controlled trials of antibiotic prescription for acute …
A systematic investigation of confirmed autoimmune loci in early-onset psoriasis reveals an association with IL2/IL21
Authors: R.B. Warren, R.L. Smith, E. Flynn, J. Bowes, S. Eyre, J. Worthington, A. Barton, C.E.M. Griffiths
Journal: British Journal of Dermatology (2011)

Many autoimmune diseases share common susceptibility loci suggesting similar underlying cellular mechanisms involved in disease expression.The purpose of this investigation was to study 21 genetic variants in 14 genes that are confirmed autoimmune loci in a cohort of patients with early-onset psoriasis.Patients with early-onset psoriasis (n = 750) and controls (n = 3531) were genotyped using the Sequenom(®) MassArray™ iPLEX Gold platform.We found strong evidence of association with two variants in the IL2/IL21 (rs6822844, genotypic P = 3·3 × 10(-4) ; rs2069778, genotypic P = 7·86 × 10(-4)) region.The findings, although requiring replication, suggest that IL2/IL21 may play a key role in the pathogenesis of psoriasis as well as in other diverse autoimmune diseases.
Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway
Authors: Koichi Inoue, Zhi-Gang Xiong
Journal: Cardiovascular Research (2009)

The presence and potential function of transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable non-selective cation channel of the TRP channel superfamily in human vascular endothelial cells, were examined. Whole-cell patch-clamp recordings showed outward-rectifying currents in human umbilical vein endothelial cells (HUVECs), which was potentiated by removing the extracellular Ca2+ and Mg2+, but inhibited by non-specific TRPM7 blocker Gd3+ or 2-aminoethoxydiphenyl borate (2-APB). TRPM7 mRNA was detected in HUVECs by RT–PCR, but TRPM6, its closest homologue, was not. Silencing TRPM7 by small interfering RNA (siRNA) decreased the level of TRPM7 mRNA and the TRPM7-like current. Interestingly, knockdown of TRPM7 with siRNA or inhibition of TRPM7 function with 2-APB increased the phosphorylation of extracellular signal-regulated kinase (ERK) and enhanced growth/proliferation of HUVECs. This enhanced cell growth/proliferation was abolished by an inhibitor of the ERK signalling pathway. In addition to cell growth/proliferation, silencing TRPM7 also increased expression of nitric oxide synthase and nitric oxide production in an ERK pathway-dependent manner. These observations suggest that TRPM7 channels may play an important role in the function of vascular endothelial cells.
Lecture Notes: Respiratory Medicine
Authors: N. Ambrosino
Journal: European Respiratory Journal (2007)

Edited by S.J. Bourke    Published by Blackwell Publishing, Oxford, UK    Pages: 232. Price: £18.99. ISBN-13: 978-1405153447

Lecture Notes: Respiratory Medicine    The time we have available to read a book is becoming shorter and shorter. This is why pocket books, to be read while travelling, are so successful. Currently, pocket books are successfully used to summarise the plots of works of fiction, but could this …
Inherited depression of arterial lipoamide dehydrogenase activity associated with susceptibility to atherosclerosis in pigeons.
Authors: T Zemplenyi, D H Blankenhorn, A J Rosenstein
Journal: Circulation Research (1975)

The activity of lipoamide dehydorgenase (E.C.1.6.4.3) was measured in arterial homogenates from very young pigeons (5-8 weeks old) known to differ in their susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly lower in the atherosclerosis-susceptible White Carneau pigeons than it was in the atherosclerosis-resistant Show Racer pigeons. Lipoamide dehydrogenase is a component of the pyruvate dehydrogenase and alpha-ketoglutarate multienzyme complexes. The first complex catalyzes the conversion of pyruvate to oxaloacetate via acetyl-CoA, and this reaction represents a crucial link between glycolysis and the Krebs cycle. The second complex is essential for the oxidative breakdown of carbohydrates, fats, and amino acids via the Krebs cycle. Reduced activity of these complexes, resulting from low activity of lipoamide dehydrogenase, favors reduction of pyruvate to lactate and a shift to glycolysis. This situation is in accord with other results obtained in avian and human arteries which appear to indicate a higher rate of glycolysis in atherosclerosis-susceptible and atherosclerotic arteries. It appears that the increased dependence of the White Carneau arteries on glycolysis, suggested by the reduced lipoamide dehydrogenase activity, facilitates the development of atherosclerosis in this pigeon strain.
Upper airway mucosa temperature in obstructive sleep apnoea/hypopnoea syndrome, nonapnoeic snorers and nonsnorers
Authors: F Series, I Marc
Journal: European Respiratory Journal (1998)

Upper airway (UA) inflammation (oedema and hyperaemia) is frequently observed in snorers and patients with sleep apnoea/hypopnoea patients. The temperature of different UA regions measured in 11 male nonsnorers, 13 nonapnoeic snorers and 10 untreated sleep apnoea/hypopnoea syndrome (SAHS) patients using infra-red video recording. Measurements were taken with the mouth open during tidal volume mouth breathing, and at the beginning and end of a 10 s end-inspiratory voluntary apnoea which followed either mouth or nasal breathing. Three measurements were obtained from the uvula and from each side of the posterior pharyngeal wall and two from each side of the soft palate. The different UA regions were characterized by their inspiratory temperature, the expiratory rewarming and the changes in UA temperature during apnoea. The temperature of the uvula was significantly lower than that of the other UA regions. For each anatomical region, there were no differences in inspiratory temperature between normals, snorers and SAHS. In normals, the expiratory rewarming was significantly higher in the uvula than in the velum and the posterior pharyngeal wall, whereas these regional differences were not observed in snorers and SAHS. The velum and posterior pharyngeal rewarming was significantly less in normals than in snorers and SAHS. During apnoea, the UA rewarming was similar to that observed during expiration. In conclusion, tissue temperature varies between the different upper airway regions and during tidal breathing and the intensity of the regional expiratory rewarming differs between normals, snorers and patients with sleep apnoea/hypopnoea syndrome.
Thyroid Hormone-Carbohydrate Interaction in the Rat
Authors: Mary Ann Forciea, Harold L. Schwartz, Howard C. Towle, Cary N. Mariash, F. E. Kaiser, J. H. Oppenheimer
Journal: Journal of Clinical Investigation (1981)

Previous studies from this laboratory have demonstrated an age-related decrease in hepatic malic enzyme (ME) levels and in the response of ME to triiodo-l-thyronine (T3). Moreover, we have recently shown a synergistic interaction of T3 and a high carbohydrate diet in the induction of this enzyme. Studies were therefore undertaken to assess the response of aging rats to a high carbohydrate diet and to test the effect of such dietary manipulations on the responsiveness of ME to T3. For this purpose, a new radio-immunoassay for ME was developed that, because of a 10-fold higher sensitivity, was particularly suited to the measurement of the low concentrations of hepatic enzyme in older animals. The level of ME per milligram of DNA fell ∼70% between 1 and 6 mo with only minor further changes demonstrated between 6 and 18 mo. In contrast, the level of ME per milligram DNA in brain was slightly increased in the older animals. Although the absolute increment of hepatic ME resulting from seven daily injections of T3 (15 μg/100 g body wt) fell with age, the ratio of the ME content per milligram DNA to that observed in control animals maintained on a regular chow diet remained relatively constant with an average value of 11.1. The responsivity of hepatic ME to a high carbohydrate, fat-free diet also decreased with age and could not be attributed exclusively to a reduction in food consumption. The age-related reduction in ME responsivity to dietary stimuli appeared to be due to a reduction in the formation of the specific messenger, (m)RNA for ME as determined in an in vitro translational assay. Our data are consistent with the following hypothesis. There is an age-related decreased hepatic responsivity to a high carbohydrate dietary stimulus. Thyroid hormone administration, as previously postulated by us, interacts with a product or an intermediate of carbohydrate metabolism in a multiplicative fashion. As a consequence, the absolute increment of ME induced by T3 administration also declines with age.
Human Factors in Highway Safety
Authors: Ross A. McFarland, Roland C. Moore
Journal: New England Journal of Medicine (1957)

Control of Host Factors through Selection of DriversMany attempts have been made to build tests for the selection of drivers around a variety of perceptual, psychomotor and psychologic characteristics. As would be expected from the discussion in the first section of this report, the results have, in general, been disappointing. The most effective tests are useful chiefly in situations in which a small group of drivers is to be chosen from a large number of candidates. In other words, it would be possible to classify drivers into high, medium and low groups, and to expect different group accident rates. . . .
Effect of perfusate [Ca2+] on cardiac sarcoplasmic reticulum Ca2+ release channel in isolated rat hearts.
Authors: A E Abdelmeguid, J J Feher
Journal: Circulation Research (1992)

The effect of perfusate [Ca2+] on the function of cardiac sarcoplasmic reticulum (CSR) was assessed by the oxalate-supported Ca2+ uptake rate of ventricular homogenates of isolated rat hearts maintained in a modified Langendorff preparation. The total Ca2+ pumping activity of the CSR was determined by using 20 microM ruthenium red or 625 microM ryanodine to close the CSR Ca2+ release channel. The homogenate Ca2+ uptake rate in the absence of ruthenium red or ryanodine decreased progressively with increasing perfusate [Ca2+] (25.7 +/- 1.2, 21.4 +/- 1.5, 17.2 +/- 1.1, and 16.3 +/- 1.2 [mean +/- SEM] nmol Ca2+.min-1.mg-1 for hearts perfused for 5 minutes with 0.2, 1.4, 2.8, and 5.6 mM Ca2+, respectively; p = 0.0001; n = 8). This depression was not observed when Ca2+ uptake was assayed in the presence of ryanodine or ruthenium red. Since the Ca2+ uptake in the presence of ryanodine or ruthenium red is determined by the Ca(2+)-ATPase, this result suggests that perfusion with varying [Ca2+] did not affect the Ca(2+)-ATPase. The observed decrease in Ca2+ uptake in the absence of ryanodine or ruthenium red is caused by an increased efflux through the ryanodine-sensitive Ca2+ release channel. When hearts perfused for 5 minutes with 0.2 or 5.6 mM Ca2+ were reperfused for 10 minutes with 1.4 mM Ca2+, homogenate Ca2+ uptake rates were restored to near control levels. These effects of perfusate Ca2+ were not direct effects, because changes in the [Ca2+] of the homogenization medium did not alter the homogenate Ca2+ uptake activity in either the presence or absence of ryanodine. The homogenate Ca2+ uptake rates were unaffected by prior active loading of the CSR with Ca2+. These results suggest a regulatory role of perfusate Ca2+ in increasing the open state of the ryanodine-sensitive Ca2+ release channel that is distinct from the beat-to-beat regulation of Ca2+ release from the CSR by Ca2+ (Ca(2+)-induced Ca2+ release).
Aprepitant, Granisetron, and Dexamethasone for Prevention of Chemotherapy-Induced Nausea and Vomiting After High-Dose Melphalan in Autologous Transplantation for Multiple Myeloma: Results of a Randomized, Placebo-Controlled Phase III Trial
Authors: Thomas Schmitt, Hartmut Goldschmidt, Kai Neben, Anja Freiberger, Johannes Hüsing, Martina Gronkowski, Markus Thalheimer, Le Hang Pelzl, Gerd Mikus, Jürgen Burhenne, Anthony D. Ho, Gerlinde Egerer
Journal: Journal of Clinical Oncology (2014)

Purpose The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial. Patients and Methods Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m 2 was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index–Emesis (FLIE) questionnaire on days −1 and 6. Results Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P &lt; .001). Conclusion The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.
Acute Poliomyelitis in Pregnancy
Authors: W. Lloyd Aycock
Journal: New England Journal of Medicine (1946)

A CLINICAL impression that poliomyelitis occurs with undue frequency during pregnancy and its possible importance in relation to susceptibility have been emphasized in previous papers.1 2 3 4 There are many reports of cases in the literature that deal with various aspects of the disease in the pregnant mother, such as effects of the disease on the mother and the fetus or obstetric problems created by the occurrence of the disease. Few reports have dealt specifically with the question of frequency of the disease in pregnancy or its significance. Within the age groups concerned pregnancy is relatively frequent and poliomyelitis is infrequent. For . . .
Evolution, mating effort, and crime
Authors: David C. Rowe
Journal: Behavioral and Brain Sciences (1995)

Abstruct Unlike some psychiatric illnesses, criminal lifestyles are not reproductive dead ends and may represent frequency-dependent adaptations. Sociopaths may gain reproductively from their greater “mating effort” relative to nonsociopaths. This mating-effort construct should be assessed directly in future studies of sociopathy. Collaboration between biologically oriented and environmentally oriented researchers is needed to investigate the biosocial basis of sociopathy.
Jejunal villous atrophy with morbid obesity: death after jejunoileal bypass.
Authors: R F Logan, A Ferguson
Journal: Gut (1982)

A 49-year-old woman with morbid obesity was found to have subtotal villous atrophy in an operative jejunal biopsy, taken when a jejunoileal bypass was created. After the operation, the patient developed marked weight loss, vomiting, hepatic failure, and a bizarre mental state with sudden losses of consciousness. Six months after the first operation the bypass was reversed but the patient developed hepatorenal failure and died one week after the second operation. The histological features of several biopsies of jejunum were typical of a gluten sensitive enteropathy. This, previously subclinical, small bowel disease may have contributed to her hepatic failure and death by interfering with jejunoileal adaptation. In the absence of any of the other, rarer, causes of villous atrophy, this woman appears to have had coeliac disease.
Meriolins, a New Class of Cell Death–Inducing Kinase Inhibitors with Enhanced Selectivity for Cyclin-Dependent Kinases
Authors: Karima Bettayeb, Oscar M. Tirado, Séverine Marionneau-Lambot, Yoan Ferandin, Olivier Lozach, Jonathan C. Morris, Silvia Mateo-Lozano, Peter Drueckes, Christoph Schächtele, Michael H.G. Kubbutat, François Liger, Bernard Marquet, Benoît Joseph, Aude Echalier, Jane A. Endicott, Vicente Notario, Laurent Meijer
Journal: Cancer Research (2007)

Abstract Protein kinases represent promising anticancer drug targets. We describe here the meriolins, a new family of inhibitors of cyclin-dependent kinases (CDK). Meriolins represent a chemical structural hybrid between meridianins and variolins, two families of kinase inhibitors extracted from various marine invertebrates. Variolin B is currently in preclinical evaluation as an antitumor agent. A selectivity study done on 32 kinases showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, with marked potency on CDK2 and CDK9. The structures of pCDK2/cyclin A/variolin B and pCDK2/cyclin A/meriolin 3 complexes reveal that the two inhibitors bind within the ATP binding site of the kinase, but in different orientations. Meriolins display better antiproliferative and proapoptotic properties in human tumor cell cultures than their parent molecules, meridianins and variolins. Phosphorylation at CDK1, CDK4, and CDK9 sites on, respectively, protein phosphatase 1α, retinoblastoma protein, and RNA polymerase II is inhibited in neuroblastoma SH-SY5Y cells exposed to meriolins. Apoptosis triggered by meriolins is accompanied by rapid Mcl-1 down-regulation, cytochrome c release, and activation of caspases. Meriolin 3 potently inhibits tumor growth in two mouse xenograft cancer models, namely, Ewing's sarcoma and LS174T colorectal carcinoma. Meriolins thus constitute a new CDK inhibitory scaffold, with promising antitumor activity, derived from molecules initially isolated from marine organisms. [Cancer Res 2007;67(17):8325–34]