tbuckley/cabot-search huggingface dataset:
Distribution of inhaled fluticasone propionate between human lung tissue and serum in vivo
Authors: N Esmailpour, P Hogger, KF Rabe, U Heitmann, M Nakashima, P Rohdewald
Journal: European Respiratory Journal (1997)

High retention of inhaled glucocorticoids in the airways means prolonged anti-inflammatory action and low delivery into the serum. The objective of this study was to investigate the retention in and distribution of inhaled fluticasone propionate (FP) between central and peripheral human lung tissue and serum in vivo. In 17 patients undergoing lung resection surgery, a single 1.0 mg dose of FP was inhaled at varying time-points (range 2.8-21.7 h) preoperatively. Peripheral and central lung tissue was obtained, and blood was drawn simultaneously. FP concentrations in central lung tissue were approximately three to four times higher than peripheral lung tissue concentrations, which in turn, exceeded those found in serum by 10 times. FP was detectable up to 21 and 16 h, respectively, after inhalation, with drug levels falling almost in parallel in peripheral lung tissue and in serum. The results of this study demonstrate that fluticasone propionate is retained in lung tissue for a long time. Serum concentrations after a single inhaled dose are low. Retention of high concentrations of fluticasone propionate in the airways may promote high topical anti-inflammatory activity.
Liposomal, Nanoparticle, and Conjugated Formulations of Anticancer Agents
Authors: William C. Zamboni
Journal: Clinical Cancer Research (2005)

Major advances in the use of liposomes, conjugates, nanoparticles, and microspheres as vehicles delivering pharmacologic agents and enzymes to sites of disease have occurred in the past 10 years ([1][1]–[3][2]). Pegylated-STEALTH liposomal doxorubicin (Doxil, Caelyx) was the first liposomal
Prostate Cancer Predisposition Loci and Risk of Metastatic Disease and Prostate Cancer Recurrence
Authors: Jiyoung Ahn, Adam S. Kibel, Jong Y. Park, Timothy R. Rebbeck, Hanna Rennert, Janet L. Stanford, Elaine A. Ostrander, Stephen Chanock, Ming-Hsi Wang, Rama D. Mittal, William B. Isaacs, Elizabeth A. Platz, Richard B. Hayes
Journal: Clinical Cancer Research (2011)

Genome-wide association studies (GWAS) have identified multiple novel prostate cancer predisposition loci. Whether these common genetic variants are associated with incident metastatic prostate cancer or with recurrence after surgical treatment for clinically localized prostate cancer is uncertain.Twelve single nucleotide polymorphisms (SNPs) were selected for study in relation to prostate metastatic cancer and recurrence, based on their genome-wide association with prostate cancer in the Cancer Genetic Markers of Susceptibility (CGEMS). To assess risk for metastatic disease, we compared genotypes for the 12 SNPs by logistic regression of 470 incident metastatic prostate cancer cases and 1,945 controls in 3 case-control studies. To assess the relationship of these SNPs to risk for prostate cancer recurrence, we used Cox regression in a cohort of 1,412 men treated for localized prostate cancer, including 328 recurrences, and used logistic regression in a case-case study, comparing 450 recurrent versus 450 nonrecurrent prostate cancer cases. Study-specific relative risks (RRs) for risk of metastatic disease and recurrence were summarized using meta-analysis, with inverse variance weights.MSMB rs10993994 (per variant allele summary RR = 1.24, 95% CI = 1.05-1.48), 8q24 rs4242382 (RR = 1.40, 95% CI = 1.13-1.75), and 8q24 rs6983267 (RR = 0.67, 95% CI = 0.50-0.89) were associated with risk for metastatic prostate cancer. None of the 12 SNPs was associated with prostate cancer recurrence.SNPs in MSMB and 8q24 which predispose to prostate cancer overall are associated with risk for metastatic prostate cancer, the most lethal form of this disease. SNPs predictive of prostate cancer recurrence were not identified, among the predisposition SNPs. GWAS specific to these 2 phenotypes may identify additional phenotype-specific genetic determinants.
Structure-Driven Developments of 26S Proteasome Inhibitors
Authors: Paweł Śledź, Wolfgang Baumeister
Journal: The Annual Review of Pharmacology and Toxicology (2016)

The 26S proteasome is a 2.5-MDa complex, and it operates at the executive end of the ubiquitin-proteasome pathway. It is a proven target for therapeutic agents for the treatment of some cancers and autoimmune diseases, and moreover, it has potential as a target of antibacterial agents. Most inhibitors, including all molecules approved for clinical use, target the 20S proteolytic core complex; its structure was determined two decades ago. Hitherto, efforts to develop inhibitors targeting the 19S regulatory particle subunits have been less successful. This is, in part, because the molecular architecture of this subcomplex has been, until recently, poorly understood, and high-resolution structures have been available only for a few subunits. In this review, we describe, from a structural perspective, the development of inhibitory molecules that target both the 20S and 19S subunits of the proteasome. We highlight the recent progress achieved in structure-based drug-discovery approaches, and we discuss the prospects for further improvement.
Portal hypertension and the outcome of surgery for hepatocellular carcinoma in compensated cirrhosis: A systematic review and meta‐analysis
Authors: Annalisa Berzigotti, Maria Reig, Juan G. Abraldes, Jaime Bosch, Jordi Bruix
Journal: Hepatology (2014)

Whether preoperative clinically significant portal hypertension (CSPH) has or not an impact on the outcome of surgery for hepatocellular carcinoma (HCC) in patients with compensated cirrhosis is debated. This systematic review assesses the impact of CSPH on the outcome of HCC in patients with compensated cirrhosis treated with surgery. We performed a systematic search of the MEDLINE database (articles published in full in English language from 1996 to October 2013) and related bibliography for studies reporting on the postoperative outcomes (3‐ and 5‐year mortality and/or early clinical decompensation) of patients with HCC and compensated cirrhosis treated with surgery according to the presence or absence of CSPH. Independent extraction of articles by two authors using predefined data fields, including study quality indicators, was used; pooled analyses were based on random‐effects models. Eleven studies in total met our inclusion criteria (eight studies for 3‐ and 5‐year postoperative mortality and eight for postoperative clinical decompensation). Moderate heterogeneity among studies for both outcomes was observed, which disappeared after pooling studies using similar methods to assess CSPH. The presence of CSPH increased the risk of 3‐ and 5‐year mortality versus absence of CSPH (pooled odds ratio [OR] for 3‐year mortality: 2.09; 95% confidence interval [CI]: 1.52‐2.88; for 5‐year mortality: 2.07; 95% CI: 1.51‐2.84). CSPH also increased the risk of postoperative clinical decompensation (pooled OR: 3.04; 95% CI: 2.02‐4.59). Conclusions : CSPH (evaluated by any method) significantly increases the risk of 3‐ and 5‐year mortality and of clinical decompensation after surgery for HCC. (H epatology 2015;61:526‐536)
Future directions and research needs.
Authors: W H Farland
Journal: Environmental Health Perspectives (1991)

In this paper, three perspectives for indoor air issues are considered: a) air inside of our homes and offices is a major component of our overall living environment and has potentially great impact on public health; b) there are important scientific questions raised specifically to indoor air that will require skills and expertise to develop and interpret research and data collection efforts; and c) from a risk assessor's point of view, the types and quality of scientific information is critical to the process of health risk assessment to risk managers to make the best decisions regarding environmental risks from indoor air. The primary focus of this presentation is to highlight suggested future directions and needs of the U.S. Environmental Protection Agency that formed the core of a report to Congress on assessment and control of indoor air pollution. The five major areas that constitute the current EPA indoor air research strategy are monitoring/building studies; health effects; source characterization/mitigation; health impact/risk assessment; and program management/technology transfer. Additionally, major trends and research needs are discussed, including greater emphasis on noncancer effects and multiple pollutants at low levels and the need for more sensitive measures for detecting adverse health effects to more effectively characterize chemically sensitive individuals and population subgroups.
Hyperoxia in acute asthma
Authors: Catherine Snelson, Bill Tunnicliffe
Journal: Thorax (2011)

time, we have an up-to-date picture of how CAP is currently managed in the UK, where this differs from guideline recommendations and where attention should be paid to lead to improvements in practice.We believe that the BTS guidelines are a reasonable translation of the available scientific evidence with regard to this topic, but we also acknowledge that they are not perfect and may not be appropriate for all settings.Inevitably, they are weakest where there is least evidence and choice of antibiotics is one such area.We would like to see the guidelines improve, but this can only occur with better evidence.This requires future funding for clinical research in this important, but research-neglected area.
Infection with the Avian-Battey Group of Mycobacteria in England and Wales
Authors: W. B. Schaefer, K. J. Birn, P. A. Jenkins, J. Marks
Journal: BMJ (1969)

Of 109 cases in England and Wales in which mycobacteria of the avian-Battey group were isolated from man 89 were considered genuine infections (including 32 with Mycobacterium avium) and six were doubtful. Almost half the significant cases were lung infections in men in dusty occupations, mostly coal miners with pneumoconiosis, and just over a quarter were non-pulmonary, mostly cervical adenitis in children. The prognosis in lung infections was serious, especially in the presence of pneumoconiosis.
Erythropoietin Biology in Cancer
Authors: Matthew E. Hardee, Murat O. Arcasoy, Kimberly L. Blackwell, John P. Kirkpatrick, Mark W. Dewhirst
Journal: Clinical Cancer Research (2006)

Erythropoietin (Epo) has long been known to be the principal hematopoietic growth factor that regulates cellular proliferation and differentiation along the erythroid lineage. Recent studies have shown that Epo is a pleiotropic cytokine that is proangiogenic and exerts broad tissue-protective effects in diverse nonhematopoietic organs. Recombinant Epo (rEpo) has been widely used in the clinic to prevent or treat malignancy-associated anemia. A series of clinical trials have documented the efficacy of rEpo in reducing RBC transfusion requirements and improving quality of life in cancer patients, and a recent meta-analysis suggested a positive effect on survival. However, two randomized trials reported negative outcomes with rEpo, as patients in the rEpo arm fared worse than their placebo-treated counterparts with respect to progression-free survival. The expression of Epo receptor (EpoR) in cancer cells has raised the possibility that exogenous rEpo may exert direct effects on tumor cells associated with the potential for stimulation of proliferation, inhibition of apoptosis, or modulation of sensitivity to chemoradiation therapy. The presence of an autocrine-paracrine Epo-EpoR system in tumors and potential effects of Epo on tumor microenvironment and angiogenesis are consistent with a complex biology for Epo-EpoR signaling in cancer that requires further research. This review describes Epo and EpoR biology, focusing on the pleiotropic effects of Epo on nonhematopoietic tissues as well as the expression and function of EpoR in cancer cells.
Interruption of the Aortic Arch Without a Patent Ductus Arteriosus
Authors: JACOB R. MORGAN, ALAN D. FORKER, RICHARD G. FOSBURG, M. KEN NEUGEBAUER, ALBERT K. ROGERS, CARL R. BEMILLER
Journal: Circulation (1970)

Complete interruption of the aortic arch without a patent ductus arteriosus is compatible with survival for many years. This is demonstrated by the case reported herein and two others reported in the literature. With no connection between the ascending and the descending aorta and with both subclavian arteries coming off the descending aorta, blood supply to the entire body, except for the head, was by retrograde flow through the vertebral arteries and left cervical collaterals. Bounding carotid pulsations with diminished arm and leg pulses are apparent in this anomaly. Surgical restoration of the continuity between the ascending and the descending aorta was successful in this case and the two previously reported cases. The surgical results of all cases of interruption or atresia of the aortic arch, including those with a patent ductus arteriosus, are reviewed, and the appearance of the ascending aorta on angiography is suggested as a possible differential point between interruption and atresia of the aortic arch.
Evolving Concepts of Asthma
Authors: Marc Gauthier, Anuradha Ray, Sally E. Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Section:ChooseTop of pageAbstract <<Introduction to the Disco...Historical AsthmaPhenotypes in AsthmaClinical and Inflammatory...Molecular/Physiologic Phe...ConclusionsReferencesCITING ARTICLES
Safe relief of rest pain that eases with activity in achillodynia by intrabursal or peritendinous steroid injection: the rupture rate was not increased by these steroid injections.
Authors: M T Read
Journal: British Journal of Sports Medicine (1999)

A history of morning and rest pain that eases with activity was found to improve after anti-inflammatory injections around the paratenon or within the Achilles bursae. The reduction in pain morbidity was significant, and the peritendinous steroid injections did not increase the rupture rate.
Public Roles of US Physicians
Authors: Russell L. Gruen, Eric G. Campbell, David Blumenthal
Journal: JAMA (2006)

3][4]6 These are at odds, however, with some education and practice environments that do not foster physicians' engagement with broader public health issues. 7,8urrently, little is known about practicing physicians' attitudes about, or the extent to which they participate in community, political, or advocacy activities.A previous attempt to define and operationalize public roles included a 1998 survey of junior family practice physicians who regarded relevant components to be assimilating into the community and its organizations, identifying and intervening in community health problems, coordinating local comm u n i t y h e a l t h r e s o u r c e s , a n d responding to particular issues of local cultural representatives when caring for patients. 9ecently, we defined physicians' public roles to be "advocacy for and participation in improving the aspects of communities that affect the health of individuals." 10We also identified a range of office-based and out-of-office tasks that may define physicians' involvement in public roles and that are compatible with busy medical practices.These activities are healthrelated and may be undertaken by phy-
Does deep water running reduce exercise-induced breast discomfort?
Authors: Deirdre E McGhee, Bruce M Power, Julie R Steele
Journal: British Journal of Sports Medicine (2007)

Aim: To establish whether exercise-induced vertical breast displacement and discomfort in women with large breasts were reduced during deep water running compared to treadmill running. Methods: Sixteen women (mean age = 32 years, range 19–43 years; mean mass = 74.1 kg, range 61–114 kg; mean height = 1.7 m, range 1.61–1.74 m), who were professionally sized to wear a C+ bra cup, were recruited as representative of women with large breasts. After extensive familiarisation, vertical breast motion of the participants was quantified as they ran at a self-selected stride rate on a treadmill and in 2.4 m deep water. Immediately after running, the subjects rated their breast discomfort and breast pain (visual analogue scale) and their perceived exertion (Borg scale). Breast discomfort, breast pain, perceived exertion, vertical breast displacement and vertical breast velocity were compared between the two experimental conditions. Results: Exercise-induced breast discomfort was significantly less and perceived exertion was significantly greater during deep water running relative to treadmill running. Although there was no significant between-condition difference in vertical breast displacement, mean peak vertical breast velocity was significantly (p&lt;0.05) less during deep water (upward mean (SD): 29.7 (14.0) cm.s −1 ; downward: 31.1 (17.0) cm.s −1 ) compared to treadmill running (upward mean (SD): 81.4 (21.7) cm.s −1 ; downward: 100.0 (25.0) cm.s −1 ). Conclusion: Deep water running was perceived as a more strenuous but comfortable exercise mode for women with large breasts. Increased comfort was attributed to reduced vertical breast velocity rather than reduced vertical breast displacement.
T Helper 2 (Th2) T Cells Induce Acute Pancreatitis and Diabetes in Immune-compromised Nonobese Diabetic (NOD) Mice
Authors: Syamasundar V. Pakala, Michael O. Kurrer, Jonathan D. Katz
Journal: The Journal of Experimental Medicine (1997)

Autoimmune diabetes is caused by the CD4+, T helper 1 (Th1) cell-mediated apoptosis of insulin-producing β cells. We have previously shown that Th2 T cells bearing the same T cell receptor (TCR) as the diabetogenic Th1 T cells invade islets in neonatal nonobese diabetic (NOD) mice but fail to cause disease. Moreover, when mixed in excess and cotransferred with Th1 T cells, Th2 T cells could not protect NOD neonates from Th1-mediated diabetes. We have now found, to our great surprise, the same Th2 T cells that produced a harmless insulitis in neonatal NOD mice produced intense and generalized pancreatitis and insulitis associated with islet cell necrosis, abscess formation, and subsequent diabetes when transferred into immunocompromised NOD.scid mice. These lesions resembled allergic inflamation and contained a large eosinophilic infiltrate. Moreover, the Th2-mediated destruction of islet cells was mediated by local interleukin-10 (IL-10) production but not by IL-4. These findings indicate that under certain conditions Th2 T cells may not produce a benign or protective insulitis but rather acute pathology and disease. Additionally, these results lead us to question the feasibility of Th2-based therapy in type I diabetes, especially in immunosuppressed recipients of islet cell transplants.
Elevated plasma norepinephrine concentrations in decompensated cirrhosis. Association with increased secretion rates, normal clearance rates, and suppressibility by central blood volume expansion.
Authors: K M Nicholls, M D Shapiro, V J Van Putten, R Kluge, H M Chung, D G Bichet, R W Schrier
Journal: Circulation Research (1985)

Plasma norepinephrine concentrations are elevated in patients with decompensated cirrhosis, and correlate inversely with urinary sodium and water excretion. Increased plasma norepinephrine concentrations may result from a decreased metabolic clearance rate or an increased secretion rate, possibly in response to a decreased "effective arterial blood volume." If the latter hypothesis is correct, plasma norepinephrine might be expected to be suppressed when central blood volume is expanded by head-out water immersion. In the present study, plasma norepinephrine secretion and clearance rates were determined by infusion of tritiated norepinephrine. Norepinephrine secretion rates were elevated in eight cirrhotic patients as compared to control subjects (1.50 +/- 0.25 vs. 0.26 +/- 0.08 micrograms/m2 per min, P less than 0.001), whereas clearance rates were similar (3.13 +/- 0.48 vs. 2.60 +/- 0.28 liters/min, NS). Baseline plasma norepinephrine concentrations were markedly elevated in the cirrhotic patients (830 +/- 136 vs. 185 +/- 12 pg/ml, P less than 0.001). Head-out water immersion significantly suppressed plasma concentrations of both norepinephrine (704 +/- 72 to 475 +/- 70 pg/ml, P less than 0.005) and epinephrine (121 +/- 33 to 57 +/- 10 pg/ml, P less than 0.05) in all seven patients studied. We conclude that the high circulating catecholamine concentrations in cirrhosis are secondary to increased secretion, rather than to decreased metabolic clearance, and are suppressible by central blood volume expansion.
Glucose-Induced Insulin Secretion in Dyslipidemic and Normolipidemic Patients With Normal Glucose Tolerance
Authors: Christophe Binnert, Myriam Genoud, Gérald Seematter, Assia Fekirini, Vincent Mooser, Gérard Waeber, Luc Tappy
Journal: Diabetes Care (2005)

The metabolic syndrome is highly prevalent in industrialized countries, where it represents a major public health burden due to the associated high risk of diabetes and cardiovascular disorders (1,2). High plasma triglyceride and low HDL cholesterol are prominent features of this syndrome (2,3). Large epidemiological studies have shown associations with both insulin resistance and low insulin secretion (4). The aim of this study was to evaluate whether the alterations of blood lipid, observed in the metabolic syndrome, are associated with alterations of insulin sensitivity or secretion in subjects with normal glucose tolerance. Glucose homeostasis was evaluated during a two-step hyperglycemic clamp in a group of dyslipidemic patients and in a group of normolipemic subjects of similar age and body weight. Subjects were studied after short-term administration of dexamethasone to evaluate reciprocal changes in insulin secretion and insulin sensitivity (5,6,7,8).

Twenty dyslipidemic subjects (13 men and 7 women) with BMI >27 kg/m2 but having normal glucose tolerance, as documented by a standard oral glucose tolerance test (fasting glycemia 94 ± 7 mg/dl, 2-h glycemia 95 ± 17 mg/dl) (9), were selected for the study. They had a mean (±SD) age of 46.6 ± 7.6 years, body …
A nationwide population-based study to determine whether coeliac disease is associated with infertility
Authors: D. Zugna, L. Richiardi, O. Akre, O. Stephansson, J. F. Ludvigsson
Journal: Gut (2010)

<h3>Background and objective</h3> Previous studies suggest that women with coeliac disease (CD) have reproductive difficulties but the data are often inconclusive and contradictory. Fertility in women with biopsy-verified CD was examined. <h3>Methods</h3> Swedish population-based cohort study. Duodenal/jejunal biopsy data on CD (Marsh III; villous atrophy (VA); n=18 005 unique women) were collected from all (n=28) pathology departments in Sweden. From this dataset, 11 495 women with CD, aged 18–45 years, were identified at some point before the end of follow-up. Multinomial logistic regression and Cox regression were used to estimate fertility in these women compared with that in 51 109 age-matched reference women. Fertility was defined as the number of children according to the Swedish Multi-Generation Register. <h3>Results</h3> During follow-up, 16 309 births occurred in women with CD and 69 245 in the reference women. The cumulative number of children slightly increased in women with CD compared with the reference group. Adjusting for age, calendar period and parity and stratifying by education, the overall fertility hazard ratio (HR) in CD was 1.03 (95% CI 1.01 to 1.05). Specifically, the fertility HR was 1.05 (95% CI 0.96 to 1.14) for CD diagnosed in women before 18 years, 1.04 (95% CI 1.01 to 1.07) for CD diagnosed in women between 18 and 45 years and 1.02 (95% CI 0.99 to 1.04) for CD diagnosed in women &gt; 45 years of age. Taking date of CD diagnosis into account, fertility was decreased 0–2 years before time of diagnosis (HR=0.63; 95% CI 0.57 to 0.70), was identical to that of controls 0–5 years subsequent to diagnosis and increased to 1.12 (95% CI 1.03 to 1.21) thereafter. <h3>Conclusion</h3> Overall, women with CD had a normal fertility, but their fertility was decreased in the last 2 years preceding CD diagnosis.