tbuckley/cabot-search huggingface dataset:
Erythema Annulare in Adults with Acute Rheumatism
Authors: J. S. Kamermann
Journal: Annals of the Rheumatic Diseases (1962)

In the winter of 1959-1960 the number of patients with acute rheumatism who applied to our Centre for treatment was larger than in former years, and most cases presented with a forme fruste of the condition.The three cases reported differed from the others in that they presented with erythema annulare (EA).The chief outward sign of erythema annulare is a series of rings about 2 mm.wide, with a diameter of 1-3 cm., pale pink to bluish-red in colour.The rings may show a festoon-like con- fluence, and may usually be observed on the trunk, and less frequently on the extremities.The fact that they are not raised above the skin surface indicates that there is little exudation, and because itching and desquamation are absent they often pass unnoticed.Sometimes the rings become fully visible only when the skin is exposed to heat or cold.The erythema is susceptible to rapid changes in shape and colour and is also influenced by emotion (Wallgren, 1935).Erythema annulare was described for the first time by Barlow (1883), who noted it in children with acute rheumatism, but as early as 1826, Rayer had called attention to the association of acute rheu- matism and skin affections (Perry, 1937).Lehndorff and Leiner (1922) and Lehndorff (1930) asserted that erythema annulare occurred only in acute rheu- matism, and only when there also existed a rheu- matic affection of the heart.In this way, the con- dition has acquired an unfavourable prognostic significance.It has been said never to occur in babies and only seldom in adults (Abt, 1935; Pelle and Massot, 1937; Ablard and Larcan, 1956a, b; Slater and Rosenbaum, 1959), but it has been observed in approximately 10 per cent. of children
ACUTE REGULATION OF TYROSINE HYDROXYLASE BY NERVE ACTIVITY AND BY NEUROTRANSMITTERS VIA PHOSPHORYLATION
Authors: R. E. Zigmond, M. A. Schwarzschild, A. R. Rittenhouse
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Severe Hypoglycemia and Cognitive Decline in Older People With Type 2 Diabetes: The Edinburgh Type 2 Diabetes Study
Authors: Insa Feinkohl, Phyu Phyu Aung, Marketa Keller, Christine M. Robertson, Joanne R. Morling, Stela McLachlan, Ian J. Deary, Brian M. Frier, Mark W.J. Strachan, Jackie F. Price
Journal: Diabetes Care (2013)

People with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Hypoglycemia is a candidate risk factor, but the direction of association between episodes of severe hypoglycemia and cognitive decline in type 2 diabetes remains uncertain.In the Edinburgh Type 2 Diabetes Study, cognitive function was assessed in 831 adults with type 2 diabetes (aged 60-75 years) at baseline and after 4 years. Scores on seven neuropsychological tests were combined into a standardized general ability factor g. Self-reported history of severe hypoglycemia at baseline (history of hypoglycemia) and at follow-up (incident hypoglycemia) was recorded.A history of hypoglycemia was reported by 9.3% of subjects, and 10.2% reported incident hypoglycemia. Incident hypoglycemia was associated with poorer cognitive ability at baseline (age- and sex-adjusted odds ratio for lowest tertile of g 2.04 [95% CI 1.25-3.31], P = 0.004). Both history of hypoglycemia and incident hypoglycemia were also associated with greater cognitive decline during follow-up (mean follow-up g adjusted for age, sex, and baseline g -0.25 vs. 0.03 [P = 0.02] and -0.28 vs. 0.04 [P = 0.01], respectively), including after addition of vascular risk factors and cardiovascular and microvascular disease to the models (-0.23 vs. 0.03 [P = 0.04] and -0.21 vs. 0.05 [P = 0.03], respectively).The relationship between cognitive impairment and hypoglycemia appeared complex, with severe hypoglycemia associated with both poorer initial cognitive ability and accelerated cognitive decline.
Effect of a diabetic environment in utero on predisposition to type 2 diabetes
Authors: Eugène Sobngwi, Philippe Boudou, Franck Mauvais-Jarvis, Hervé Leblanc, Gilberto Velho, Patrick Vexiau, Raphaël Porcher, Samy Hadjadj, Richard Pratley, P Antonio Tataranni, Fabien Calvo, Jean-François Gautier
Journal: The Lancet (2003)
Detection and localization of multiple epicardial electrical generators by a two-dipole ranging technique.
Authors: D M Mirvis, F W Keller, R E Ideker, J W Cox, R F Dowdie, D G Zettergren
Journal: Circulation Research (1977)

The ability of a numerical procedure to detect and to localize two experimentally induced, epicardial dipolar generators was tested in 24 isolated, perfused rabbit heart preparations, suspended in an electrolyte-filled spherical tank. Electrocardiograms were recorded from 32 electrodes on the surface of the test chamber before and after placement of each of two epicardial burns. The second lesion was located either 180 degrees, 90 degrees, or 45 degrees from the first. Signals were processed by iterative routines that computed the location of one or two independent dipoles that best reconstruced the observed surface potentials. The computed single dipole acounting for 99.68% of root mean sequare (RMS) surface potential recorded after the first burn was located 0.26 +/- 0.10 cm from the centroid of the lesion. Potentials recorded after the second lesions were fit with two dipoles that accounted for 99.36 +/- 1.51% of RMS surface potentials and that were located 0.42 +/- 0.26 cm and 0.57 +/- 0.49 cm from the centers of the corresponding burn. Seventy-one percent of computed dipoles were located within the visible perimeter of the burn. Thus, two simultaneously active dipolar sources can be detected and accurately localized by rigorous study of the generated electrical field.
What's new in the physiopathology of acne?
Authors: D.H. Suh, H.H. Kwon
Journal: British Journal of Dermatology (2015)

There are four central factors that contribute to acne physiopathology: the inflammatory response, colonization with Propionibacterium acnes, increased sebum production and hypercornification of the pilosebaceous duct. In addition, research in the areas of diet and nutrition, genetics and oxidative stress is also yielding some interesting insights into the development of acne. In this paper we review some of the most recent research and novel concepts revealed in this work, which has been published by researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology. We discuss the implications of their findings (particularly in terms of opportunities to develop new therapies), highlight interrelationships between these novel factors that could contribute to the pathology of acne, and indicate where gaps in our understanding still exist.
n-Butyrate inhibition of hyaluronate synthesis in cultured human fibroblasts.
Authors: T J Smith
Journal: Journal of Clinical Investigation (1987)

The effects of the short-chain aliphatic carboxylic acid, n-butyrate, on glycosaminoglycan (GAG) accumulation were studied in cultured human skin fibroblasts. Normal fibroblast cultures were grown to confluence, shifted to a medium without or with n-butyrate for 24 h, labeled with either [3H]acetate or [3H]glucosamine and analyzed for [3H]GAG and [3H]hyaluronate accumulation. Accumulation was stimulated at low concentrations (0.1-1 mM) by up to 27%. Higher concentrations of n-butyrate (greater than 1 mM) inhibited [3H]GAG by up to 70-90%. This effect was maximal at 10 mM and half-maximal at 3 mM. Propionate had similar effects but was less potent. Parallel studies conducted in colonic fibroblasts revealed that n-butyrate could markedly inhibit [3H]GAG accumulation in that cell type as well. These effects were rapid, occurring within 3 h of treatment, and were reversible. Chondroitin sulfate accumulation was unaffected by the compound. A pulse-chase study failed to demonstrate any effect on [3H]GAG degradation.
The cost-effectiveness of bevacizumab plus cisplatin and gemcitabine (BCG) compared with pemetrexed plus cisplatin (PC) induction treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in Germany.
Authors: H. Bischoff, A. Hermes, U. Gatzemeier, D. F. Heigener, S. Cesaro-Tadic, S. Walzer
Journal: Journal of Clinical Oncology (2010)

e18054 Background: New treatment options for advanced NSCLC can offer improved survival over standard chemotherapy (CT) but should also offer value for money. Bevacizumab, a humanized monoclonal antibody directed against VEGF has been shown to increase overall survival and time to progression in patients (pts) with advanced NSCLC when combined with CT compared with CT alone. Pemetrexed, a thymidylate synthase inhibitor, in combination with cisplatin has shown survival benefit over cisplatin plus gemcitabine. This analysis evaluated the cost-effectiveness of BCG compared with PC in Germany. Methods: A Markov model was used to evaluate the average costs and benefits of treating pts with advanced or recurrent NSCLC with either BCG or PC. The characteristics of an average German hospital pt (80 kg) were applied. The model assumes pts move from pre-progressive to progressed disease to death, according to a set of transition probabilities derived from the respective pivotal trials and appropriate indirect comparison methodology. Drug costs assume underlying CT (CG and PC) is given for up to 6 cycles, but that bevacizumab is administered until progression. The model estimates average survival, drug, administration and progression costs per pt treated with either BCG or PC and the incremental cost-effectiveness ratio. Results: BCG treatment resulted in a mean survival of 1.51 versus 1.31 years with PC. Generic gemcitabine is now available in Germany and the total cost of therapy was €29,199 for BCG compared with €20,369 for PC, resulting in an acceptable cost per life year gained of €44,070 with BCG. Conclusions: BCG gives value for money when compared to chemotherapies such as pemetrexed in Germany. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche AstraZeneca, Lilly, Merck, Roche Roche Bayer, Lilly, Merck, Novartis, Roche
Performance of Helical Computed Tomography in Unselected Outpatients with Suspected Pulmonary Embolism
Authors: Arnaud Perrier, Nigel Howarth, Dominique Didier, Pierre Loubeyre, Pierre-François Unger, Philippe de Moerloose, Daniel Slosman, Alain Junod, Henri Bounameaux
Journal: Annals of Internal Medicine (2001)

Background: Helical computed tomography (CT) is commonly used to diagnose pulmonary embolism, although its operating characteristics have been insufficiently evaluated. Objective: To assess the sensitivity and specificity of helical CT in suspected pulmonary embolism. Design: Observational study. Setting: Emergency department of a teaching and community hospital. Patients: 299 patients with clinically suspected pulmonary embolism and a plasma d-dimer level greater than 500 µg/L. Intervention: Pulmonary embolism was established by using a validated algorithm that included clinical assessment, lower-limb compression ultrasonography, lung scanning, and pulmonary angiography. Measurements: Sensitivity, specificity, and likelihood ratios of helical CT and interobserver agreement. Helical CT scans were withheld from clinicians and were read 3 months after acquisition by radiologists blinded to all clinical data. Results: 118 patients (39%) had pulmonary embolism. In 12 patients (4%), 2 of whom had pulmonary embolism, results of helical CT were inconclusive. For patients with conclusive results, sensitivity of helical CT was 70% (95% CI, 62% to 78%) and specificity was 91% (CI, 86% to 95%). Interobserver agreement was high (κ = 0.823 to 0.902). The false-negative rate was lower for helical CT used after initial negative results on ultrasonography than for helical CT alone (21% vs. 30%). Use of helical CT after normal results on initial ultrasonography and nondiagnostic results on lung scanning had a false-negative rate of only 5% and a false-positive rate of only 7%. Conclusion: Helical CT should not be used alone for suspected pulmonary embolism but could replace angiography in combined strategies that include ultrasonography and lung scanning.
Physical Activity, Cardiovascular Risk Factors, and Mortality Among Finnish Adults With Diabetes
Authors: Gang Hu, Pekka Jousilahti, Noël C. Barengo, Qing Qiao, Timo A. Lakka, Jaakko Tuomilehto
Journal: Diabetes Care (2005)

OBJECTIVE—The aim of this study was to examine both single and joint associations of physical activity and conventional cardiovascular risk factors with total and cardiovascular mortality among patients with diabetes. RESEARCH DESIGN AND METHODS—We prospectively followed 3,708 Finnish patients with type 2 diabetes aged 25–74 years. Physical activity, smoking status, blood pressure, height, weight, and serum cholesterol level were determined at baseline. Cox proportional hazard models were used to estimate single and joint effects of physical activity and other cardiovascular risk factors on the risk of mortality. RESULTS—During a mean follow-up of 18.7 years, 1,423 deaths were recorded, 906 of which were due to cardiovascular disease. Moderate or high levels of physical activity were associated with decreased total and cardiovascular mortality, whereas higher levels of BMI and blood pressure and current smoking were associated with increased total and cardiovascular mortality. High serum cholesterol levels also increased cardiovascular mortality. The protective effect of physical activity was consistent in diabetic patients with any levels of BMI, blood pressure, total cholesterol, and smoking. CONCLUSIONS—A moderate or high level of physical activity was associated with a reduced risk of total and cardiovascular mortality among patients with type 2 diabetes. The favorable association of physical activity with longevity was observed regardless of the levels of BMI, blood pressure, total cholesterol, and smoking.
Autophagy in cell death: an innocent convict?
Authors: Beth Levine, Junying Yuan
Journal: Journal of Clinical Investigation (2005)

The visualization of autophagosomes in dying cells has led to the belief that autophagy is a nonapoptotic form of programmed cell death. This concept has now been evaluated using cells and organisms deficient in autophagy genes. Most evidence indicates that, at least in cells with intact apoptotic machinery, autophagy is primarily a pro-survival rather than a pro-death mechanism. This review summarizes the evidence linking autophagy to cell survival and cell death, the complex interplay between autophagy and apoptosis pathways, and the role of autophagy-dependent survival and death pathways in clinical diseases.
Reversal of Multidrug Resistance in Human Colon Cancer Cells Expressing the Human MDR1 Gene by Liposomes in Combination With Monoclonal Antibody or Verapamil
Authors: S. Sela, S. R. Husain, J. W. Pearson, D. L. Longo, A. Rahman
Journal: JNCI Journal of the National Cancer Institute (1995)

Colorectal cancer is a major cause of cancer-related mortality in the world and the second leading cause of neoplastic death in the United States. A major obstacle in the chemotherapy of this neoplasm is the emergence of multidrug resistance that is frequently associated with the expression of P-glycoprotein (p170) encoded by MDR1 (also known as PGY1) genes. Previously, we demonstrated that liposome-encapsulated doxorubicin is more cytotoxic than free doxorubicin in human promyelocytic leukemia and human breast cancer cells with the multidrug-resistant phenotype.Our purpose was to investigate modulation of multidrug resistance by liposome-encapsulated vincristine (VCR) in a drug-resistant human colon cancer cell line HT-29mdr1 and the potentiation of this modulation in combination with monoclonal antibody MRK-16 or verapamil.HT-29 parental cells and HT-29mdr1 cells were exposed to free VCR or liposome-encapsulated VCR alone or in combination with MRK-16 or verapamil. Cytotoxicity of cells after various treatments was determined by neutral red staining, and cellular content of VCR was measured by using radiolabeled VCR; p170 expression of cells was assessed by azidopine.HT-29mdr1 cells express a high amount of p170, thus conferring sixfold to sevenfold resistance to VCR compared with the parent cell line. Liposome-encapsulated VCR lowers drug resistance in HT-29mdr1 cells fourfold; IC50 values (concentration that causes 50% reduction in cell number) were 12.5 +/- 2.5 ng/mL compared with 42.5 +/- 5.0 ng/mL with free VCR. IC50 values for free VCR with empty liposomes were 25 +/- 1.25 ng/mL. The combination of MRK-16 and free VCR produced a twofold increase in cytotoxicity over free VCR in p170-expressing cells; the combination of MRK-16 and liposome-encapsulated VCR produced a 10-fold potentiation of cytotoxicity. toxicity. Nonspecific monoclonal antibody NR-LU-10 had no effect on cytotoxicity of HT-29mdr1 cells with free VCR or liposome-encapsulated VCR. The combination of 1.5 microM verapamil potentiated the cytotoxicity of free VCR ninefold to 10-fold, IC50 values reduced to 5.0 +/- 1.5 ng/mL, and in combination with liposome-encapsulated VCR, IC50 values reduced to 2.5 +/- 1.0 ng/mL, demonstrating a 15- to 17-fold potentiation of cytotoxicity. There were no significant differences in drug accumulation in HT-29mdr1 cells when treated with liposome-encapsulated VCR or free VCR. Liposomes inhibited the photoaffinity labeling of azidopine to p170 HT-29mdr1 cells.Liposome encapsulation of VCR effectively modulates multidrug resistance in human colon cancer cells and may become an important modality in treatment for colon cancers.
A Phase I Study of Pemetrexed (ALIMTA) and Cyclophosphamide in Patients with Locally Advanced or Metastatic Breast Cancer
Authors: Christian Dittrich, Lubos Petruzelka, Pavel Vodvarka, Margit Gneist, Filip Janku, Tamara Kysela, Allen Melemed, Jane Latz, Lorinda Simms, Kurt Krejcy
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Determine the maximum tolerated dose (MTD) of pemetrexed and cyclophosphamide combination therapy for patients with locally advanced or metastatic breast cancer. Experimental Design: Patients with locally advanced or metastatic breast cancer and WHO performance status 0 to 2 were eligible. Pemetrexed (range, 400-2,400 mg/m2) was administered on day 1 of a 21-day schedule followed by cyclophosphamide (range, 400-800 mg/m2). Folic acid and vitamin B12 supplementation began 1 to 2 weeks before the first pemetrexed dose. Results: Fifty-seven pretreated patients were enrolled and received 342 cycles (median, 4 cycles; range, 1-26) through 14 dose levels. The MTD of pemetrexed was 2,400 mg/m2 (combined with cyclophosphamide, 600 mg/m2) with dose-limiting toxicities of grade 4 neutropenia with grade 4 infection and grade 3 diarrhea. Other grade 3 or 4 toxicities included (febrile) neutropenia, thrombocytopenia, anemia, elevated alanine aminotransferase/aspartate aminotransferase, and diarrhea. Pharmacokinetic analysis indicated that pemetrexed clearance and central volume of distribution were 40% lower than single-agent reference data, yielding a 68% increase in total systemic exposure and a 56% increase in maximal plasma concentration. Among the 50 patients evaluable for efficacy, 13 (26%) patients had a partial response and 17 (34%) patients had stable disease. Conclusions: Pemetrexed was generally well tolerated. The observed toxicities were consistent with the known toxicity profiles of pemetrexed and cyclophosphamide. Considering the MTD and the toxicity and efficacy results in this and prior studies, a low (600 mg/m2) and a high (1,800 mg/m2) dose of pemetrexed with cyclophosphamide (600 mg/m2) will be evaluated in the consecutive prospective randomized phase II study.
Re: Felix K.-H. Chun, Thomas Steuber, Andreas Erbersdobler, et al. Development and Internal Validation of a Nomogram Predicting the Probability of Prostate Cancer Gleason Sum Upgrading Between Biopsy and Radical Prostatectomy Pathology. Eur Urol 2006;49:820–26
Authors: Ian Beckley, Masood A. Khan
Journal: European Urology (2007)
Effect of exercise on repolarisation abnormalities in patients with asymptomatic QT prolongation
Authors: D.-K. WU, J. K BISSETT, J. I WATSON, J. BAKER
Journal: Cardiovascular Research (1984)

Patients with congenital QT prolongation have an increased incidence of ventricular arrhythmias and sudden death. Altered sympathetic tone has been suggested as an important contributing factor in this syndrome. Although some patients with an increased QT interval and arrhythmias have an abnormal QT response during exercise, the effect of exercise has not been reported in patients with acquired QT prolongation without clinical manifestations. The purpose of this study was to determine the pattern of QT change with exercise in patients with QT prolongation without exercise-induced arrhythmias in order to: 1) determine the most frequent response in this group; 2) observe the effect of posture on QT changes; and 3) compare the rate of QT change with a control group. Treadmill exercise testing was performed in 10 patients (mean age 52.1 ±8.0 years) with a QTc greater than 0.44 s; the results were compared with 14 patients with a normal QTc (mean age 45.8±12.1 years). Patients with an increased QT interval at rest experienced a significant reduction in QT interval during exercise (0.315±0.030 s vs 0.394±0.046 s standing at rest; P<0.01), as cycle length was decreased from 0.732±0.175 s to 0.489±0.062 s. Patients in the control group had a similar change in QT interval (0.297±0.015 s vs 0.359±0.029 s standing at rest (P<0.01), with a comparable change in cycle length 0.733±0.097 s vs 0.511 ±0.059 s. The slope of QT interval versus R-R interval was not significantly different (0.295±0.109 vs 0.259±0.100 s). Changes in QT and R-R intervals between supine and standing positions were similar in both groups. The results demonstrate that patients with QT prolongation without exercise-induced arrhythmias have a significant decrease in QT interval during upright exercise. The change in QT interval is not significantly different from that observed in a control group with normal QT measurements when similar changes in heart rate are produced by treadmill exercise. The results suggest that repolarisation abnormalities in this group respond in a normal manner to changes in autonomic tone produced by upright posture and treadmill exercise.