tbuckley/cabot-search huggingface dataset:
Hypoxia Inducible Factor-1 Activation by Prolyl 4-Hydroxylase-2 Gene Silencing Attenuates Myocardial Ischemia Reperfusion Injury
Authors: Ramesh Natarajan, Fadi N. Salloum, Bernard J. Fisher, Rakesh C. Kukreja, Alpha A. Fowler
Journal: Circulation Research (2005)

Hypoxia inducible factor-1 (HIF-1) regulates changes in transcription of key genes such as inducible NO synthase (iNOS) in hypoxic/ischemic environments. In normoxia, HIF-1 activation is controlled by HIF-1alpha-prolyl 4-hydroxylases, which target HIF-1alpha for ubiquitination and proteasomal degradation. We hypothesized that normoxic HIF-1 preservation could attenuate cardiac ischemia/reperfusion injury via a preconditioning effect. HIF-1 preservation was achieved by using small interfering RNA (siRNA) to silence murine HIF-1alpha-prolyl-4 hydroxylase-2 (PHD2). PHD2 siRNA reduced PHD2 mRNA expression 89+/-1.5% (P<0.001) in a time- and concentration-dependent manner in normoxic murine microvascular endothelial cells (EC). PHD2 silencing in normoxic EC stabilized HIF-1alpha protein levels while significantly increasing HIF-1 transcriptional activity and iNOS mRNA expression. Wild-type mice infused with PHD2 siRNA (1.5 microg/g body weight) showed a 61+/-2.4% (P<0.05) reduction in cardiac PHD2 mRNA within 24 hours. In addition HIF-1alpha protein levels and HIF-1-dependent iNOS mRNA levels were increased. PHD2 siRNA-transfected hearts from wild-type mice (n=6) subjected to 30 minutes ischemia followed by 60 minutes reperfusion exhibited reduced infarct size when compared with saline-treated controls (9.7+/-1.9% versus 31.6+/-1.8%, respectively, P<0.0001, n=6) and to control mice transfected with a nontargeting siRNA control (28.4+/-3.0%, P<0.0001, n=6). Hearts from iNOS knockout mice receiving PHD2 siRNA by identical injection protocol (n=6) exhibited infarct size indistinguishable from saline controls (28.7+/-1.3%). These results show that in vitro and in vivo, PHD2 silencing using a siRNA strategy produces transcriptionally active HIF-1. Normoxic activation of HIF-1 in hearts following in vivo PHD2 siRNA administration attenuates reperfusion injury via an iNOS-dependent pathway.
Infection and remodelling: a 21st century model of bronchiectasis?
Authors: C. Ward, K. Rydell-Törmänen, G. Westergren-Thorsson, L.T. Eriksson, H. Walters
Journal: European Respiratory Journal (2011)

on-cystic fibrosis bronchiectasis is defined according to morphological criteria as the permanent dilatation of bronchi.Numerous causes have been identified, with a common end-point of repeated, vicious cycles of infection, inflammation and airway structural changes [1].There is a general belief that the incidence of bronchiectasis is falling, but this is poorly researched [1,2].When assessed, prevalence estimates vary widely between populations from 3.7 per 100,000 children in New Zealand to 52 per 100,000 adults in the USA [1]. Clinical descriptions of bronchiectasis made over 200 yrs ago byRene ´The ´ophile Hyacinthe Laennec, the inventor of the stethoscope, vividly reflect the considerable associated morbidity: ''This affection of the bronchia is always produced by chronic catarrh, or by some other disease attended by long, violent, and often repeated fits of coughing'' [3].
NT‐proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT‐proBNP substudy
Authors: Franz Hartmann, Milton Packer, Andrew J.S. Coats, Michael B. Fowler, Henry Krum, Paul Mohacsi, Jean L. Rouleau, Michal Tendera, Alain Castaigne, Jürgen Trawinski, Ildiko Amann‐Zalan, Silke Hoersch, Hugo A. Katus
Journal: European Journal of Heart Failure (2004)
The Impact of Prostate Size, Median Lobe, and Prior Benign Prostatic Hyperplasia Intervention on Robot-Assisted Laparoscopic Prostatectomy: Technique and Outcomes
Authors: Andy C. Huang, Keith J. Kowalczyk, Nathanael D. Hevelone, Stuart R. Lipsitz, Hua-yin Yu, Blakely A. Plaster, Channa A. Amarasekara, William D. Ulmer, Yin Lei, Stephen B. Williams, Jim C. Hu
Journal: European Urology (2011)
Impact of posttransplantation G-CSF on outcomes of allogeneic hematopoietic stem cell transplantation
Authors: Hanna J. Khoury, Fausto R. Loberiza, Olle Ringdén, A. John Barrett, Brian J. Bolwell, Jean Yves Cahn, Richard E. Champlin, Robert Peter Gale, Gregory A. Hale, Alvaro Urbano-Ispizua, Rodrigo Martino, Philip L. McCarthy, Pierre Tiberghien, Leo F. Verdonck, Mary M. Horowitz
Journal: Blood (2005)
MRI Evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer
Authors: Constance D. Lehman, Constantine Gatsonis, Christiane K. Kuhl, R. Edward Hendrick, Etta D. Pisano, Lucy Hanna, Sue Peacock, Stanley F. Smazal, Daniel D. Maki, Thomas B. Julian, Elizabeth R. DePeri, David A. Bluemke, Mitchell D. Schnall
Journal: New England Journal of Medicine (2007)

Even after careful clinical and mammographic evaluation, cancer is found in the contralateral breast in up to 10% of women who have received treatment for unilateral breast cancer. We conducted a study to determine whether magnetic resonance imaging (MRI) could improve on clinical breast examination and mammography in detecting contralateral breast cancer soon after the initial diagnosis of unilateral breast cancer. A total of 969 women with a recent diagnosis of unilateral breast cancer and no abnormalities on mammographic and clinical examination of the contralateral breast underwent breast MRI. The diagnosis of MRI-detected cancer was confirmed by means of biopsy within 12 months after study entry. The absence of breast cancer was determined by means of biopsy, the absence of positive findings on repeat imaging and clinical examination, or both at 1 year of follow-up. MRI detected clinically and mammographically occult breast cancer in the contralateral breast in 30 of 969 women who were enrolled in the study (3.1%). The sensitivity of MRI in the contralateral breast was 91%, and the specificity was 88%. The negative predictive value of MRI was 99%. A biopsy was performed on the basis of a positive MRI finding in 121 of the 969 women (12.5%), 30 of whom had specimens that were positive for cancer (24.8%); 18 of the 30 specimens were positive for invasive cancer. The mean diameter of the invasive tumors detected was 10.9 mm. The additional number of cancers detected was not influenced by breast density, menopausal status, or the histologic features of the primary tumor. MRI can detect cancer in the contralateral breast that is missed by mammography and clinical examination at the time of the initial breast-cancer diagnosis. (ClinicalTrials.gov number, NCT00058058 [ClinicalTrials.gov].).
CT-quantified emphysema in male heavy smokers: association with lung function decline
Authors: F. A. A. Mohamed Hoesein, B. de Hoop, P. Zanen, H. Gietema, C. L. J. J. Kruitwagen, B. van Ginneken, I. Isgum, C. Mol, R. J. van Klaveren, A. E. Dijkstra, H. J. M. Groen, H. M. Boezen, D. S. Postma, M. Prokop, J.-W. J. Lammers
Journal: Thorax (2011)

<h3>Background</h3> Emphysema and small airway disease both contribute to chronic obstructive pulmonary disease (COPD), a disease characterised by accelerated decline in lung function. The association between the extent of emphysema in male current and former smokers and lung function decline was investigated. <h3>Methods</h3> Current and former heavy smokers participating in a lung cancer screening trial were recruited to the study and all underwent CT. Spirometry was performed at baseline and at 3-year follow-up. The 15th percentile (Perc15) was used to assess the severity of emphysema. <h3>Results</h3> 2085 men of mean age 59.8 years participated in the study. Mean (SD) baseline Perc15 was −934.9 (19.5) HU. A lower Perc15 value correlated with a lower forced expiratory volume in 1 s (FEV<sub>1</sub>) at baseline (r=0.12, p&lt;0.001). Linear mixed model analysis showed that a lower Perc15 was significantly related to a greater decline in FEV<sub>1</sub> after follow-up (p&lt;0.001). Participants without baseline airway obstruction who developed it after follow-up had significantly lower mean (SD) Perc15 values at baseline than those who did not develop obstruction (−934.2 (17.1) HU vs −930.2 (19.7) HU, p&lt;0.001). <h3>Conclusion</h3> Greater baseline severity of CT-detected emphysema is related to lower baseline lung function and greater rates of lung function decline, even in those without airway obstruction. CT-detected emphysema aids in identifying non-obstructed male smokers who will develop airflow obstruction.
Cartilage turnover assessed with a newly developed assay measuring collagen type II degradation products: influence of age, sex, menopause, hormone replacement therapy, and body mass index
Authors: U Mouritzen
Journal: Annals of the Rheumatic Diseases (2003)

Cartilage normally has a slow turnover but in arthritis increased metabolism results in degradation of the tissue.To assess cartilage turnover in a sample of the general population by an assay measuring cartilage derived urinary collagen type II (CTX-II) C-telopeptide degradation products.CTX-II concentrations were measured in urine samples from 615 healthy men and women aged 20-87 years, and the influence of age, sex, menopause, hormone replacement therapy (HRT), and body mass index (BMI) was assessed.CTX-II concentrations showed age dependent variations, with notable differences between men and women. Mean (SD) CTX-II concentration in postmenopausal women (220 (118) ng/mmol, n=25) was significantly higher than in an age matched group of premenopausal women (112 (79) ng/mmol, n=26, p<0.001). CTX-II concentration in women using HRT (118 (57) ng/mmol, n=50) was significantly lower than in an age and BMI matched group of women not receiving HRT (215 (99) ng/mmol, n=50, p<0.001). In subjects with a BMI >or=25 kg/m(2), CTX-II concentrations were significantly higher than in those with a BMI <25 kg/m(2) (185 (114) v 148 (91) ng/mmol, p<0.001).Cartilage turnover, as assessed by measuring urinary degradation products of CTX-II varies considerably with age, and significant differences between CTX-II levels in men and women as well as in pre- and postmenopausal women are found. Further studies are required to validate the marker for assessing cartilage degradation in arthritis.
Hyperglycemia rapidly suppresses flow-mediated endothelium- dependent vasodilation of brachial artery
Authors: Hiroaki Kawano, Takeshi Motoyama, Osamu Hirashima, Nobutaka Hirai, Yuji Miyao, Tomohiro Sakamoto, Kiyotaka Kugiyama, Hisao Ogawa, Hirofumi Yasue
Journal: Journal of the American College of Cardiology (1999)
Obliterative bronchiolitis in haematopoietic stem cell transplantation: can it be treated?
Authors: D. H. Bryant
Journal: European Respiratory Journal (2005)

Allogeneic and autologous haematopoietic stem cell (HSC) transplantation are now both established as principal forms of treatment for patients with acute or chronic leukaemia, aplastic anaemia and various immunodeficiency syndromes, as well as various nonhaematological malignancies and auto-immune disorders 1–3. However, major limitations to the successful use of HSC transplantation include respiratory complications and graft versus host disease. Lung dysfunction occurs in up to 50% of subjects after HSC transplantation, and pulmonary complications are among the most common causes of morbidity and mortality after this procedure 4.

Obliterative bronchiolitis (OB) is the most common noninfectious respiratory complication after HSC transplantation 5, 6, and usually develops as a late complication (after the first 100 days) and at the same time as chronic graft versus host disease develops. The onset of OB is usually 6–12 months post-transplant, with the clinical severity ranging from asymptomatic to fulminant and fatal. The lack of a precise definition and uniform diagnostic criteria has led to variations in the reported incidence, between 0 and 50%, with commonly quoted figures being between 5 and 20% 7, 8. Although OB has been described after autologous HSC transplantation 9, this is a rare complication, a fact usually attributed to the absence of chronic graft versus host disease after autologous HSC transplantation.

The most commonly identified risk factor for OB after HSC transplantation is chronic graft versus host disease, but other risk factors include human leukocyte antigen mismatch or use of an unrelated donor, use of busulfan or methotrexate, increased age, male sex, cigarette smoking and the presence of airflow limitation prior to transplantation 6, 8, 10. …
Acitretin is converted to etretinate only during concomitant alcohol intake
Authors: F. Grønhøj Larsen, B. Steinkjer, P. Jakobsen, A. Hjorter, P.B. Brockhoff, F. Nielsen‐Kudsk
Journal: British Journal of Dermatology (2000)

Background Acitretin has replaced etretinate in the treatment of various disorders of keratinization due to a considerably shorter terminal half-life. Possible esterification of acitretin to etretinate in the presence of ethanol has been reported. Objectives To determine the plasma concentrations of etretinate as a metabolite in patients with various disorders of keratinization after multiple acitretin dosing, and to assess the influence of alcohol consumption using a questionnaire. In addition, to study the influence of alcohol consumption on the risk of metabolic formation of etretinate. Patients/methods Eighty-six acitretin (Neotigason®, Roche)-treated outpatients from three centres provided pre-dose (trough) samples for determining plasma concentrations of acitretin and its metabolites 13-cis-acitretin and etretinate. Patients received acitretin doses of between 0·1 and 1·3 mg kg−1 daily. The concentrations of etretinate, acitretin and 13-cis-acitretin were determined by reverse-phase high-performance liquid chromatography. Results Of the 86 patients, 30 had detectable plasma etretinate levels. No etretinate was found in 20 patients who reported that they never drank alcohol, while etretinate was found in all 16 patients with an average weekly alcohol consumption of > 200 g ethanol, corresponding to about 15 U (1 U equals half a pint of standard beer or a wine glass of non-fortified wine). Etretinate was detected in 14 of 50 patients with a moderate weekly alcohol intake of up to 200 g ethanol. A trend linking higher alcohol intake with both higher risk of etretinate formation and higher etretinate levels was observed. The study also revealed that the ethylesterification only relates to acitretin (13-trans-) and not to the main metabolite 13-cis-acitretin, although the latter compound showed higher plasma trough concentration levels at steady state. Conclusions Owing to the teratogenic potential and possible side-effects of oral retinoids, fertile women especially should be informed about the importance of strict alcohol abstinence during treatment and for at least 2 months after stopping therapy. In case of non-compliance with alcohol abstinence a post-therapy contraceptive period of 2–3 years should be recommended.
Adenine arabinoside 5'-monophosphate in patients with chronic hepatitis B: comparison of the efficacy in patients with high and low viral replication.
Authors: P Marcellin, M Pouteau, M A Loriot, N Boyer, F Degos, P Cales, L Bettan, Y Bacq, H Coppere, J D Grange
Journal: Gut (1995)

This study compared the response to adenine arabinoside 59-monophosphate (ARA AMP) in 60 patients with chronic hepatitis B according to the pretreatment serum hepatitis B virus DNA concentration. The level of hepatitis B virus replication was defined as low (30 patients) or high (30 patients) when serum hepatitis B virus DNA concentration was below or above 100 pg/ml, respectively. Patients received a 28 day course of ARA AMP and a second course of ARA AMP was given six months later to patients with persistent hepatitis B virus replication. At the end of the first course of ARA AMP, 11 of the patients (37%) with low replication and one of the patients (3%) with high replication became negative for hepatitis B virus DNA (p = 0.0012); five of the patients (17%) with low replication and none of the patients with high replication had HBe seroconversion (p = 0.06). Two of these five patients lost HBsAg. Kinetics of serum hepatitis B virus DNA during treatment showed a considerable but transient antiviral effect of ARA AMP. Three of 32 retreated patients became negative for hepatitis B virus DNA and one patient had HBe seroconversion. In conclusion, ARA AMP exerts a considerable but transient antiviral effect on hepatitis B virus. Complete and sustained inhibition of hepatitis B virus replication was only obtained in the patients with low hepatitis B virus replication.
Randomized Trial of [131I] Metuximab in Treatment of Hepatocellular Carcinoma After Percutaneous Radiofrequency Ablation
Authors: Huijie Bian, Jia-Sheng Zheng, Gang Nan, Rui Li, Changsheng Chen, Cai-Xia Hu, Yang Zhang, Bin Sun, Xi-Long Wang, Shi-Chang Cui, Jiao Wu, Jing Xu, Ding Wei, Xiaoyong Zhang, Haichun Liu, Wuwei Yang, Yong Ding, Jing Li, Zhi-Nan Chen
Journal: JNCI Journal of the National Cancer Institute (2014)

To assess the efficacy of combining radioimmunoconjugate [131I] metuximab with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) treatment compared with RFA alone, a single-center randomized controlled trial was conducted on 127 patients with Barcelona Clinic Liver Cancer staging system (BCLC) classifications of 0–B stage. Patients received either RFA followed by [131I] metuximab (n = 62) or RFA alone (n = 65). The primary outcome was overall tumor recurrence. Statistical tests were two-sided. The one- and two-year recurrence rates in the combination group were 31.8% and 58.5%, whereas those in the RFA group were 56.3% and 70.9%, respectively. The median time to overall tumor recurrence was 17 months in the combination group and 10 months in the RFA group (P = .03). The RFA-[131I] metuximab treatment showed a greater antirecurrence benefit than RFA in the metuximab target (ie, CD147)–positive subpopulation (P = .007). [131I] metuximab may yield prevention of tumor recurrence after RFA.
Lymphatic cysts of the colon
Authors: T. G. Girdwood, L. D. Philp
Journal: Gut (1971)

A patient with a lymphatic cyst of the descending colon is reported. He underwent segmental resection of the colon. The clinical features, pathology, radiology, and treatment of these lesions are reviewed. It is emphasized that these cysts are very rare and cannot be diagnosed radiologically, but must be included in the differential diagnosis of polypoid lesions of the colon.
Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity
Authors: S. D Dorn, O. S Palsson, S. I M Thiwan, M. Kanazawa, W C. Clark, M. A L van Tilburg, D. A Drossman, Y. Scarlett, R. L Levy, Y. Ringel, M. D Crowell, K. W Olden, W. E Whitehead
Journal: Gut (2007)

<b>Objective:</b> The aim was to determine whether lower visceral pain thresholds in irritable bowel syndrome (IBS) primarily reflect physiological or psychological factors. <b>Methods:</b> Firstly, 121 IBS patients and 28 controls underwent balloon distensions in the descending colon using the ascending methods of limits (AML) to assess pain and urge thresholds. Secondly, sensory decision theory analysis was used to separate physiological from psychological components of perception: neurosensory sensitivity (p(A)) was measured by the ability to discriminate between 30 mm Hg vs 34 mm Hg distensions; psychological influences were measured by the report criterion—that is, the overall tendency to report pain, indexed by the median intensity rating for all distensions, independent of intensity. Psychological symptoms were assessed using the Brief Symptom Inventory (BSI). <b>Results:</b> IBS patients had lower AML pain thresholds (median: 28 mm Hg vs 40 mm Hg; p&lt;0.001), but similar neurosensory sensitivity (median p(A): 0.5 vs 0.5; p = 0.69; 42.6% vs 42.9% were able to discriminate between the stimuli better than chance) and a greater tendency to report pain (median report criterion: 4.0 ("mild" pain) vs 5.2 ("weak" pain); p = 0.003). AML pain thresholds were not correlated with neurosensory sensitivity (r = −0.13; p = 0.14), but were strongly correlated with report criterion (r = 0.67; p&lt;0.0001). Report criterion was inversely correlated with BSI somatisation (r = −0.26; p = 0.001) and BSI global score (r = −0.18; p = 0.035). Similar results were seen for the non-painful sensation of urgency. <b>Conclusion:</b> Increased colonic sensitivity in IBS is strongly influenced by a psychological tendency to report pain and urge rather than increased neurosensory sensitivity.
A pilot study of a long acting somatostatin analogue for the treatment of refractory rheumatoid arthritis
Authors: D Paran, O Elkayam, A Mayo, H Paran, M Amit, M Yaron, D Caspi
Journal: Annals of the Rheumatic Diseases (2001)

To evaluate the efficacy and safety of a long acting somatostatin analogue in a subset of patients with refractory rheumatoid arthritis (RA).Ten patients with active, refractory RA, who had failed to respond to at least four disease modifying antirheumatic drugs (DMARDs), were treated with monthly intramuscular injections of 20 mg of a long acting preparation of octreotide (Sandostatin-LAR) for three months. They were evaluated every two weeks in an open label pilot study. The primary measure of clinical response was the American College of Rheumatology criteria for a 20% improvement in measures of disease activity (ACR 20).Eight patients completed the 14 week trial, while two patients received only one or two doses of the somatostatin analogue, but were eligible for evaluation. On an intention to treat basis 6/10 patients responded: four patients met the ACR 20 criteria at weeks 6-10, while two patients continued to improve with time, and met the ACR 50 and 70 criteria respectively, at week 14. On evaluation of the 10 patients as a group, a significant improvement (p<0.05) was noted in the mean visual analogue scales of pain, doctor's and patient's global assessment of disease activity, and in the mean number of swollen joints. Adverse effects were minor: transient bloating and loose stools, an urticarial rash (n=1), and a transient increase of liver enzymes (n=1).Treatment with a long acting somatostatin analogue led to significant clinical improvement in a subset of patients with active, refractory RA. The treatment was relatively safe and well tolerated. Further large, placebo controlled studies are required to evaluate this drug as a potential DMARD for patients with RA.
Rapid modulation of electrolyte transport in Caco-2 cell monolayers by enteropathogenic <i>Escherichia coli</i> (EPEC) infection
Authors: G K Collington, I W Booth, S Knutton
Journal: Gut (1998)

Background and aims —The pathophysiology of enteropathogenic Escherichia coli (EPEC) diarrhoea remains uncertain. EPEC adhere to enterocytes and transduce signals which produce a characteristic “attaching and effacing” (A/E) lesion in the brush border membrane. The present in vitro study was designed to determine whether signal transduction by EPEC also influences electrolyte transport. Methods —Caco-2 cell monolayers were rapidly infected with wild type EPEC strain E2348/69, or the signal transduction-defective mutant 14.2.1(1), and mounted in Ussing chambers. Results —Strain E2348/69 stimulated a rapid but transient increase in short circuit current ( I sc) which coincided with A/E lesion formation; this I sc response was absent on infection with strain 14.2.1(1). While the initial rise in I sc induced by E2348/69 was partially (∼35%) dependent on chloride, the remainder possibly represents an influx of sodium and amino acid(s) across the apical membrane. Conclusions —The study directly shows that, after initial adhesion, EPEC induce major alterations in host cell electrolyte transport. The observed I sc responses indicate a rapid modulation of electrolyte transport in Caco-2 cells by EPEC, including stimulation of chloride secretion, for which signal transduction to host cells is a prerequisite.