tbuckley/cabot-search huggingface dataset:
Cellular adhesion molecules in chronic urticaria: modulation of serum levels occurs during levocetirizine treatment
Authors: M. Caproni, W. Volpi, B. Giomi, D. Torchia, E. Del Bianco, P. Fabbri
Journal: British Journal of Dermatology (2006)

Some antihistamines are capable of reducing levels of adhesion molecules in wealing tissues of patients with chronic urticaria (CU).To determine if 6 weeks of therapy with levocetirizine 5 mg once daily would also induce any decrease in serum levels of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial leucocyte adhesion molecule-1 (ELAM-1) or P-selectin in subjects with CU and chronic autoimmune urticaria.Thirty-six patients with CU (18 with positive and 18 with negative autologous serum skin test) were studied, together with 10 control healthy subjects. All patients received levocetirizine 5 mg daily. Serum soluble cellular adhesion molecule (CAM) levels were determined by immunoenzymatic assay before and after the end of the study period. Disease activity was recorded according to the EAACI/GA(2)LEN/EDF scoring system.After levocetirizine therapy CAM levels decreased in patients with CU, significantly in the cases of ELAM-1 and P-selectin. Patients' clinical scores improved during regular antihistamine therapy.Levocetirizine 5 mg daily demonstrated a broad anti-inflammatory effect in patients with CU. The significant decrease in serum levels of ELAM-1 and P-selectin might reflect the inhibitory activity on neutrophil rolling and extravasation towards inflamed skin.
Reduction by Hyperbaric Oxygenation of the Mortality from Ventricular Fibrillation Following Coronary Artery Ligation
Authors: WILLIAM M. CHARDACK, ANDREW A. GAGE, ANTHONY J. FEDERICO, JOHN K. CUSICK, PAUL J. H. MATSUMOTO, EDWARD H. LANPHIER
Journal: Circulation Research (1964)

The effect of the inhalation of hyperbaric oxygen on the incidence of ventricular fibrillation following ligation of the circumflex coronary artery was studied in 151 dogs weighing 17 kg or more. Fifty-two per cent of the animals in the control group (room air, 1 atm abs) survived the challenge of this ligation. Survival increased to 60.4, 70, and 77.8% in the groups given 100% oxygen at an ambient pressure of 1, 2, and 4 atm abs, respectively. The orderly progression in the proportion of survivals is impressive but only approaches statistical significance. The results of these experiments are less dramatic than those previously reported by others. They do point out the need for cautious clinical trial in rigidly controlled series.
Decreased expression of miR-146a and miR-155 contributes to an abnormal Treg phenotype in patients with rheumatoid arthritis
Authors: Qihui Zhou, Sonja Haupt, Johannes T Kreuzer, Ariane Hammitzsch, Fabian Proft, Carla Neumann, Jan Leipe, Matthias Witt, Hendrik Schulze-Koops, Alla Skapenko
Journal: Annals of the Rheumatic Diseases (2014)

Objectives MicroRNAs (miRNAs) have been implicated in the pathogenesis of autoimmune diseases, not least for their critical role in the regulation of regulatory T cell (Treg) function. Deregulated expression of miR-146a and miR-155 has been associated with rheumatoid arthritis (RA). We therefore investigated miR-146a and miR-155 expression in Tregs of patients with RA and their possible impact on Treg function and disease activity. Methods Expression of miR-146a and miR-155 was assessed in RA patients and controls. MiRNA expression was correlated with disease activity and expression of target genes. Interference with biological activity of miRNAs was evaluated in functional Treg assays. Results Diminished upregulation of miR-146a and miR-155 in response to T cell stimulation was found in Tregs of RA patients. Diminution of miR-146a expression was observed in particular in patients with active disease, and correlated with joint inflammation. In patients with active RA, Tregs demonstrated a pro-inflammatory phenotype characterised by inflammatory cytokine expression. This was due to an augmented expression and activation of signal transducer and activator transcription 1 (STAT1), a direct target of miR-146a. Conclusions Our results suggest that in RA miR-146a facilitates a pro-inflammatory phenotype of Tregs via increased STAT1 activation, and contributes thereby to RA pathogenesis.
Given the chance I'd start all over again
Authors: Robert Souhami
Journal: BMJ (2006)

Medicine is based on altruism, science, and human interest. Like most medical students, this is what attracted me and it still does. The aim is to preserve the good health of individuals and the general population. The aspirations are of excellent care, progress, and change. I find the continuing movement, and certainty that we will know more, inspirational and energising. Medicine is remarkable in its clinical and scientific breadth and its fusion with other disciplines and interests. Much of medicine grows from basic biology, but medical research and practice is also linked to physics, chemistry, statistics, population science, sociology, and politics. It's remarkable, for example, that new technical platforms allow quick identification of genetic patterns that in future may influence treatment given to individual patients and that this, in turn, will raise ethical and political issues for society at large. 

Whatever interests and personality you have, there is probably an aspect of medicine to suit you. The diversity can be confusing for a student and young doctor thinking about a career. When I qualified I didn't know what would be the best path to choose. I quickly found that I would get most satisfaction from clinical medicine. 

Throughout my career I have met clinicians and scientists who have set the standards that I …
A PRELIMINARY REPORT ON THE CONTINUED POST-HOSPITAL USE OF TRANQUILIZING DRUGS
Authors: ROBERT J. WOLFF, DORIS M. COLACINO
Journal: American Journal of Psychiatry (1961)

A sample of patients discharged from a state hospital was interviewed at regular intervals; this preliminary report includes information obtained at the 6 months' follow-up. In addition to an evaluation of observed, objective well-being ("adjustment"), information was obtained from the patients concerning their continued use of tranquilizing medicine. 1. very large percentage of patients are discharged with the recommendation that they continue on a regime of tranquilizing medication. 2. As time goes on, the percentage of patients who follow this advice decreases significantly, and even those who report that they continue to use the tranquilizing drugs become less "regular" in their medical regime. 3. In this study no conclusive evidence could be found that patients remaining on a tranquilizing drug did any "better" than those who did not: there is no significant difference in the rehospitalization rate, nor is there a significant difference in their observable functioning in the community. Therefore where the tranquilizing drugs have shown their effectiveness in the hospital, for the post-hospital period other means than purely medical treatment seem more effective in promoting recovery. 4. Many patients seek the advice of a physician in the community, under whose care they continue their tranquilizing drug regime. Nevertheless, even after 6 months, there is a significant number who apparently can get their original prescriptions refilled for a long time without the supervision of a local physician. 5. The study was able to show that with relatively little effort on the part of a few professional workers with discharged patients, a closer cooperation with local individuals and agencies (physicians, psychiatrists, clinic, etc.) can be obtained, showing as a result a higher percentage of patients who continued to take prescribed drugs as well as a higher percentage who take them "regularly."
Type I and II Endometrial Cancers: Have They Different Risk Factors?
Authors: Veronica Wendy Setiawan, Hannah P. Yang, Malcolm C. Pike, Susan E. McCann, Herbert Yu, Yong-Bing Xiang, Alicja Wolk, Nicolas Wentzensen, Noel S. Weiss, Penelope M. Webb, Piet A. van den Brandt, Koen van de Vijver, Pamela J. Thompson, Brian L. Strom, Amanda B. Spurdle, Robert A. Soslow, Xiao-ou Shu, Catherine Schairer, Carlotta Sacerdote, Thomas E. Rohan, Kim Robien, Harvey A. Risch, Fulvio Ricceri, Timothy R. Rebbeck, Radhai Rastogi, Jennifer Prescott, Silvia Polidoro, Yikyung Park, Sara H. Olson, Kirsten B. Moysich, Anthony B. Miller, Marjorie L. McCullough, Rayna K. Matsuno, Anthony M. Magliocco, Galina Lurie, Lingeng Lu, Jolanta Lissowska, Xiaolin Liang, James V. Lacey, Laurence N. Kolonel, Brian E. Henderson, Susan E. Hankinson, Niclas Håkansson, Marc T. Goodman, Mia M. Gaudet, Montserrat Garcia-Closas, Christine M. Friedenreich, Jo L. Freudenheim, Jennifer Doherty, Immaculata De Vivo, Kerry S. Courneya, Linda S. Cook, Chu Chen, James R. Cerhan, Hui Cai, Louise A. Brinton, Leslie Bernstein, Kristin E. Anderson, Hoda Anton-Culver, Leo J. Schouten, Pamela L. Horn-Ross
Journal: Journal of Clinical Oncology (2013)

Purpose Endometrial cancers have long been divided into estrogen-dependent type I and the less common clinically aggressive estrogen-independent type II. Little is known about risk factors for type II tumors because most studies lack sufficient cases to study these much less common tumors separately. We examined whether so-called classical endometrial cancer risk factors also influence the risk of type II tumors. Patients and Methods Individual-level data from 10 cohort and 14 case-control studies from the Epidemiology of Endometrial Cancer Consortium were pooled. A total of 14,069 endometrial cancer cases and 35,312 controls were included. We classified endometrioid (n = 7,246), adenocarcinoma not otherwise specified (n = 4,830), and adenocarcinoma with squamous differentiation (n = 777) as type I tumors and serous (n = 508) and mixed cell (n = 346) as type II tumors. Results Parity, oral contraceptive use, cigarette smoking, age at menarche, and diabetes were associated with type I and type II tumors to similar extents. Body mass index, however, had a greater effect on type I tumors than on type II tumors: odds ratio (OR) per 2 kg/m 2 increase was 1.20 (95% CI, 1.19 to 1.21) for type I and 1.12 (95% CI, 1.09 to 1.14) for type II tumors (P heterogeneity &lt; .0001). Risk factor patterns for high-grade endometrioid tumors and type II tumors were similar. Conclusion The results of this pooled analysis suggest that the two endometrial cancer types share many common etiologic factors. The etiology of type II tumors may, therefore, not be completely estrogen independent, as previously believed.
MicroRNA Regulation of Cardiovascular Development
Authors: Kimberly R. Cordes, Deepak Srivastava
Journal: Circulation Research (2009)

The transcriptional regulation of cardiovascular development requires precise spatiotemporal control of gene expression, and heterozygous mutations of transcription factors have frequently been implicated in human cardiovascular malformations. A novel mechanism involving posttranscriptional regulation by small, noncoding microRNAs (miRNAs) has emerged as a central regulator of many cardiogenic processes. We are beginning to understand the functions that miRNAs play during essential biological processes, such as cell proliferation, differentiation, apoptosis, stress response, and tumorigenesis. The identification of miRNAs expressed in specific cardiac and vascular cell types has led to the discovery of important regulatory roles for these small RNAs during cardiomyocyte differentiation, cell cycle, conduction, vessel formation, and during stages of cardiac hypertrophy in the adult. Here, we overview the recent findings on miRNA regulation in cardiovascular development and report the latest advances in understanding their function by unveiling their mRNA targets. Further analysis of miRNA function during cardiovascular development will allow us to determine the potential for novel miRNA-based therapeutic strategies.
Predictors of health-related quality of life of European food-allergic patients
Authors: J. Saleh-Langenberg, N. J. Goossens, B. M. J. Flokstra-de Blok, B. J. Kollen, G. N. van der Meulen, T. M. Le, A. C. Knulst, M. Jedrzejczak-Czechowicz, M. L. Kowalski, E. Rokicka, P. Starosta, B. de la Hoz Caballer, S. Vazquez-Cortés, I. Cerecedo, L. Barreales, R. Asero, M. Clausen, A. DunnGalvin, J. O'. B. Hourihane, A. Purohit, N. G. Papadopoulos, M. Fernandéz-Rivas, L. Frewer, P. Burney, E. J. Duiverman, A. E. J. Dubois
Journal: Allergy (2015)

Although food allergy has universally been found to impair HRQL, studies have found significant differences in HRQL between countries, even when corrected for differences in perceived disease severity. However, little is known about factors other than disease severity which may contribute to HRQL in food-allergic patients. Therefore, the aim of this study was to identify factors which may predict HRQL of food-allergic patients and also to investigate the specific impact of having experienced anaphylaxis and being prescribed an EAI on HRQL.A total of 648 European food-allergic patients (404 adults, 244 children) completed an age-specific questionnaire package including descriptive questions. Multivariable regression analyses were performed to develop models for predicting HRQL of these patients.For adults, the prediction model accounted for 62% of the variance in HRQL and included perceived disease severity, type of symptoms, having a fish or milk allergy, and gender. For children, the prediction model accounted for 28% of the variance in HRQL and included perceived disease severity, having a peanut or soy allergy, and country of origin. For both adults and children, neither experiencing anaphylaxis nor being prescribed an epinephrine auto-injector (EAI) contributed to impairment of HRQL.In this study, food allergy-related HRQL may be predicted to a greater extent in adults than in children. Allergy to certain foods may cause greater HRQL impairment than others. Country of origin may affect HRQL, at least in children. Experiencing anaphylaxis or being prescribed an EAI has no impact on HRQL in either adults or children.
Squeezing tubes: a case of remodeling and regulation Coronary reserve in hypertensive heart disease
Authors: B Schwartzkopff
Journal: Cardiovascular Research (1998)

Time for primary review 35 days. 

Essential hypertension is a main risk factor for left ventricular hypertrophy (LVH), ischemic heart disease and hypertensive cardiomyopathy [1]. In addition to the increased prevalence of atherosclerotic stenoses in epicardial arteries, hypertensive subjects with no relevant coronary artery disease or LVH have impaired coronary vasodilator reserve [2, 3]that has been reported to correlate with scintigraphic evidence of myocardial ischemia [4].

Impaired coronary reserve could be an important factor for inadequate delivery of oxygen and substrate to myocytes, precipitating myocardial ischemia and contributing to deterioration of myocardial function [2–4]. The potential mechanisms of impaired coronary reserve include abnormal processes of contraction and relaxation of a structurally remodeled myocardium, increased extravascular compressive forces, rheologic factors, metabolic factors as well as functional and structural alterations of the intramyocardial coronary arteries and arterioles (Fig. 1). The purpose of the present review is to discuss the pathophysiological mechanisms that may be involved in reduced vasodilator capacity in human hypertensive heart disease and to report about therapeutic interventions.



Fig. 1 
Potential factors to influence coronary reserve in hypertensive heart disease.



In the coronary venous blood, oxygen content is about 5 ml/100 ml, which corresponds to about 25–30% saturation and a p O2 of 18–25 mm Hg. Thus, given significant oxygen extraction, any relevant additional oxygenation can only be made available by a proportional increase in coronary blood flow. The normal heart can increase its blood flow by a factor of 4 to 5 [2–5]. Coronary autoregulation enables the heart to keep coronary flow unchanged over a wide range of perfusion pressures (from ∼50 to 120 mm Hg) (review [5, 6]). This is reflected by a pressure–flow relationship with a central portion running parallel to the pressure axis that is followed by a steep increase in flow …
Acute effects of light-emitting diodes on muscle fatigue during isometric exercise in patients with COPD: A pilot study
Authors: Eduardo Foschini Miranda, Paulo Henrique Marchetti, Ernesto Cesar Pinto Leal Junior, Simone Dal Corso
Journal: European Respiratory Journal (2012)

Background: Patients with chronic obstructive pulmonary disease (COPD) are susceptible to early muscle fatigue. Light-emitting diodes (LEDs) have been used to minimize muscle fatigue in athletes and healthy subjects. Aim: To investigate the acute effects of LEDs on muscle fatigue and perception of effort in patients with COPD during isometric endurance test of the quadriceps femoris (QF). Methods: Ten patients (VEF1 50 ± 13% of predicted) underwent a single LED and placebo (PL) application, 48 h apart, in a randomized, cross-over design. The LED and PL were applied in three localized areas of the QF (rectus femoris, vastus lateralis, and vastus medialis). Before and after exposure to LED and PL, patients performed an isometric endurance test (80% of the maximum voluntary isometric contraction) until the limit of tolerance concomitant to surface electromyography recording (median frequency as mean outcome). The slope obtained from linear regression analysis of the median frequency (MF) over endurance time was also used as an endurance index. Results: Endurance time increased significantly after exposure to LED (from 26 ± 2s to 53 ± 5s) as compared to PL (from 23 ± 3s to 30 ± 4s) (F = 64, P = 0.0001). A greater decline in MF was observed during isometric endurance test after placebo, compared to LED (F = 14.6, P = 0.004). The slope of the MF over time was lower post-LED compared to post-placebo (-0.7±0.3 vs. -1.5±0.8; P = 0.004). The dyspnea score corrected for endurance time was lower post-LED (P = 0.008), but similar for fatigue both post-LED and post-PL. Conclusion: A single application of LED minimizes muscle fatigue and increases isometric endurance time.
Fatigue is associated with high circulating leptin levels in chronic hepatitis C
Authors: T Piche
Journal: Gut (2002)

<b>Background and aims:</b> Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor α (TNF-α). <b>Methods:</b> Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-α. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients. <b>Results:</b> Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) <i>v</i> 17.7 (16.9); p&lt;0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) <i>v</i> 6.4 (4.1) ng/ml; p&lt;0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (<i>r</i>=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (<i>r</i>=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (<i>r</i>=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients. <b>Conclusions:</b> Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.
Luteolin Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis; Inhibition of Endothelial Cell Survival and Proliferation by Targeting Phosphatidylinositol 3′-Kinase Activity
Authors: Eleni Bagli, Maria Stefaniotou, Lucia Morbidelli, Marina Ziche, Konstantinos Psillas, Carol Murphy, Theodore Fotsis
Journal: Cancer Research (2004)

Abstract In an attempt to identify phytochemicals contributing to the well-documented preventive effect of plant-based diets on cancer incidence and mortality, we have previously shown that certain flavonoids inhibit in vitro angiogenesis. Here, we show that the flavonoid luteolin inhibited tumor growth and angiogenesis in a murine xenograft model. Furthermore, luteolin inhibited vascular endothelial growth factor (VEGF)-induced in vivo angiogenesis in the rabbit corneal assay. In agreement, luteolin inhibited both VEGF-induced survival and proliferation of human umbilical vein endothelial cells (HUVECs) with an IC50 of about 5 μmol/L. Luteolin inhibited VEGF-induced phosphatidylinositol 3′-kinase (PI3K) activity in HUVECs, and this inhibition was critical for both the antisurvival and antimitotic affects of the compound. Indeed, luteolin abolished VEGF-induced activation of Akt, a downstream target of PI3K conveying both survival and mitotic downstream signals. Because overexpression of a constitutively active form of Akt rescued HUVECs only from the antisurvival effects of luteolin, the result indicated that luteolin targeted mainly the survival signals of the PI3K/Akt pathway. With regard to its antimitotic activity, luteolin inhibited VEGF-induced phosphorylation of p70 S6 kinase (S6K), a downstream effector of PI3K responsible for G1 progression. Indeed, VEGF-induced proliferation of HUVECs was sensitive to rapamycin, an inhibitor of p70 S6K activation. Surprisingly, luteolin did not affect VEGF-induced phosphorylation of extracellular signal-regulated kinase 1/2 mitogen-activated protein kinases, a pathway that is considered important for the mitotic effects of VEGF. Thus, blockade of PI3K by luteolin was responsible for the inhibitory effects of the compound on VEGF-induced survival and proliferation of HUVECs. The antisurvival effects of luteolin were mediated via blockage of PI3K/Akt-dependent pathways, whereas inhibition of the PI3K/p70 S6K pathway mediated the antimitotic effects of the compound.