tbuckley/cabot-search huggingface dataset:
Effects of inspiratory muscle training in patients with gastroesophageal reflux disease
Authors: Esther Studart da Fonseca, Patrícia Carvalho Bezerra, Maria do Socorro Quintino Farias, Vasco Pinheiro Diógenes Bastos, Andrea da Nóbrega Cirino Nogueira, Miguel Ângelo Nobre Souza
Journal: European Respiratory Journal (2014)

The gastroesophageal reflux disease (GERD) is caused by acid reflux of gastric contents into the esophagus-peptic or supraesophageal estruture. The antireflux barrier is dependent on the integrity of both Lower Esophageal Sphincter-LES and the crural diaphragm. OBJECTIVE:The aim of this randomized study was to evaluate the effect of inspiratory muscle training in patients with erosive esophagitis.METHOD:20 subjects with past history of GERD were allocated to a control (C group) and an experimental group (T group) and underwent clinical evaluation by endoscopy (EGD),manovacuometry,high-resolution manometry and pH monitoring before and after IMT with 50% of their Maximum Inspiratory Pressure (MIP) three times a week, once a day during eight weeks. Diseases that could affect the study were excluded. Personal information and medical history were obtained by a questionnaire.Student t and Wilcoxon Test were used to analyze the data.RESULTS: 3 males and 7 females-T group,aged from 43,20 ± 3,23 years and 5 males and 5 females- C group,aged 41,70±3,59 years.A significant increase of MIP (76,90±6,6% to 105,60±8,6% ρ=0.002 ;T group) versus (87,00±7,6% to 94,20±9,5% p=0,11;C group),frequency reduction of throat cleaning (2-4/week to
Immune, metabolic and cytokine status in allergic rhinitis
Authors: Oksana Kolenchukova, Svetlana Smirnova, Andrey Savchenko, Sergey Tereshchenko
Journal: European Respiratory Journal (2013)

Aim: To determine immune, metabolic and cytokine status in patients with allergic rhinitis (AR).  Material and Methods: We studied 37 patients with AR and 71 healthy in ages from 25 to 45 years. Subpopulation composition in blood lymphocytes was evaluated by ductal cytometry using monoclonal antibodies. We determined Ig (A, M, G, E), concentration of circulating immune complexes (CIC). Cytokin status was determined by ELISA. The activity of NAD(P)-dependent dehydrogenases in lymphocytes by bioluminescent method.  Results: We found in AR increase of leukocytes, NK and B-cells. We marked the lowering of lymphocytes, T-cells, CD4+ and CD4+/CD8+ compared to control. CIC increase compared to control. Cytokine status showed higher of IL-1β, IL-4, IL-6, IL-8 in serum and nasal washout in AR compared to control. In AR we determined higher INF-α in serum and in nasal washout against control.  We marked the increase of the activity in such enzymes as G6PDH, NADP-dependent reaction of MDH, NAD-dependent reactions of MDH and LDG and NADH-dependent reaction of MDH and decrease in the level of such enzymes as G3DH, NADP-dependent reaction of GDH and NADPH-dependent reaction of GDH in AR compared to control.  Conclusion: We should mention an important role of metabolic processes in immune system cells in homeostasis. Speed and intensity of immune reactions depend on the initial state of lymphocyte metabolism. The changes in the activity of intracellular enzymes show the increase of intensity of energy and plastic processes in blood lymphocytes in AR as compared to control.
Abstract 517: Intracoronary Mesenchymal Stem Cells (MSCs) Improve Regional Function with a Differential Effect on Glycolytic and Mitochondrial Metabolic Enzymes in Chronic Hibernating Myocardium
Authors: Brian Page, Rebeccah F Young, Gen Suzuki, Te-Chung Lee, John M Canty
Journal: Circulation (2007)

Background: Statins and fibroblast growth factor improve function without altering myocardial perfusion by normalizing the downregulation of mitochondrial metabolic enzymes that are characteristic ...
The epidemiology of severe Streptococcus pyogenes associated disease in Europe
Authors: T  L Lamagni, A Efstratiou, J Vuopio-Varkila, A Jasir, C Schalén
Journal: Eurosurveillance (2005)

Several European countries reported outbreaks of severe disease caused by Streptococcus pyogenes in the late 1980s. This marked a departure from the previous decades, where very few such outbreaks were noted. These changes in disease occurrence formed part of a global phenomenon, the reasons for which have yet to be explained. Results of surveillance activities for invasive S. pyogenes infection within Europe over the past fifteen years identified further increases in many countries. However, variations in surveillance methods between countries preclude robust comparisons being made, illustrating the need for a unified surveillance strategy across Europe. This was finally embodied in the Strep-EURO programme, introduced in 2002.
Abstract 1775: Identification of small molecule inhibitors of HSF1 stress pathway activation in cancer cells
Authors: Emmanuel de Billy, Nicola Chessum, Robert Te Poele, Jennifer Smith, Lorenzo Zani, Swee Sharp, Mark Stubbs, Wynne Aherne, Keith Jones, Paul Workman
Journal: Cancer Research (2014)

Abstract Heat Shock Factor 1 (HSF1) is a key transcription factor involved in proteostasis and response to stress, as well as being implicated in many diseases including cancer. Up-regulation of its activity by environmental stress or oncogenesis leads to transcriptional induction of genes involved in diverse cellular processes supporting the cancer state, including proteostasis, proliferation, survival and metastasis. Inhibition of HSF1 is therefore potentially beneficial for cancer treatment, but HSF1 is not technically druggable. We developed a high-throughput cell-based reporter gene assay to screen a library of small-molecule kinase inhibitors and identified 3 compound series as validated inhibitors of HSF1 activation by the HSP90 inhibitor 17-AAG. Further characterization of imidazo[1,2-b]pyridazine compounds showed inhibition of HSF1 target gene expression and the ability to mimic other features of the HSF1 knockdown phenotype. Using these tool compounds and by siRNA knockdown of HSF1 expression we demonstrate that HSF1 inhibition leads to cell cycle arrest and enhances the antiproliferative effect of 17-AAG. In addition, we show that HSP90 inhibition induces HSF1 phosphorylation at two serine residues, Ser326 and Ser320, highlighting the importance of Ser320 phosphorylation in HSP72 up-regulation by 17-AAG-induced HSF1 activation, and show that this activation is inhibited by our tool compounds. Our findings support the optimization and development of small-molecule inhibitors of the HSF1 pathway for cancer treatment. Note: This abstract was not presented at the meeting. Citation Format: Emmanuel de Billy, Nicola Chessum, Robert Te Poele, Jennifer Smith, Lorenzo Zani, Swee Sharp, Mark Stubbs, Wynne Aherne, Keith Jones, Paul Workman. Identification of small molecule inhibitors of HSF1 stress pathway activation in cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1775. doi:10.1158/1538-7445.AM2014-1775
Isochromosome 17q in Blast Crisis of Chronic Myeloid Leukemia and in Other Hematologic Malignancies Is the Result of Clustered Breakpoints in 17p11 and Is Not Associated With Coding TP53 Mutations
Authors: Thoas Fioretos, Bodil Strömbeck, Therese Sandberg, Bertil Johansson, Rolf Billström, Åke Borg, Per-Gunnar Nilsson, Herman Van Den Berghe, Anne Hagemeijer, Felix Mitelman, Mattias Höglund
Journal: Blood (1999)
Neo-adjuvant radiation, cisplatin, 5-FU +/− paclitaxel in locally advanced esophageal cancer
Authors: K. S. Roof, J. Coen, T. J. Lynch, C. D. Wright, P. Fidias, C. G. Willett, N. C. Choi
Journal: Journal of Clinical Oncology (2004)

4042 Background: A phase I-II study of neo-adjuvant cisplatin, 5-FU, paclitaxel and radiation (PFT-R) performed at our institution yielded encouraging pathologic complete response (pCR) rates, but with significant toxicity. This retrospective study was designed to examine the results of our experience with PFT-R compared to our experience with cisplatin, 5-FU and RT (PF-R) in patients with locally advanced esophageal cancer. Methods: We searched the MGH cancer registry for all patients with esophageal cancer treated with radiation (RT) and chemotherapy between 1994–2002. Records of patients treated with curative, neo-adjuvant therapy were examined for chemotherapeutic regimen. The outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Most patients received two cycles of either cisplatin 25 mg/m2, 5-FU 1000 mg/m2 or cisplatin 20 mg/m2, 5-FU 800 mg/m2 and taxol 100 mg/m2 with a median RT dose of 54 Gy. Results: 177 patients were treated with a curative neo-adjuvant approach. 166 (94%) were treated with PF-R (N=82) or PFT-R (N=84). 16 patients (PF=8, PFT=8) treated with neo-adjuvant intent did not have surgical resection of their tumor. The pCR rate for all patients was 37 %. There was no difference between PF-R (40%) and PFT-R (33%). There was no difference in median survival between PF-R and PFT-R with an overall median survival of 24 months. After a median follow-up of 54 months for surviving patients overall survival at 3 years was 40 % with no significant difference PF-R (39 %) and PFT-R (42 %). There were 12 treatment related deaths (7%), 6 in each treatment group. There were no differences in the incidence of ≥ Grade 3 toxicities PF-R (79%), PFT-R (80%). Conclusions: The addition of paclitaxel to neo-adjuvant PF-R as delivered in this regimen failed to improve pCR rates or overall survival. Our results do not support the use of this regimen of concurrent neoadjuvant PFT-R in patients with esophageal cancer. No significant financial relationships to disclose.
Abstract 12990: Dephosphorylation of the Z-Disc Protein Syndecan-4 Activates Pro-Hypertrophic Calcineurin-NFAT Signaling in the Myocardium
Authors: Ida G Lunde, Alexandra V Finsen, Hilde Jarstadmarken, Heidi Kvaloy, Almira Hasic, Ivar Sjaastad, Theis Tonnesen, Sarah A Wilcox-Adelman, Cathrine R Carlson, Christensen A G
Journal: Circulation (2010)

The signaling mechanisms involved in myocardial hypertrophy are poorly understood. We have previously linked syndecan-4, a transmembrane proteoglycan localized to the Z-discs and focal adhesions in cardiomyocytes, to myocardial hypertrophy. Mice lacking syndecan-4 do not develop concentric hypertrophy after aortic banding (AB). Here we demonstrate that syndecan-4 anchors and activates the pro-hypertrophic calcineurin A-Nuclear Factor of Activated T-cells (CnA-NFAT) signaling pathway. In syndecan-4 KO AB, NFATc4 activation and expression of NFAT-target genes BNP and RCAN1–4 were significantly lower than in WT AB. Conversely, overexpression of syndecan-4 in HEK293 cells and treatment of cardiomyocytes with a cell-permeable syndecan-4- derived peptide activated NFATc4. Immunoprecipitations showed increased association between CnA, its co-activator calmodulin and syndecan-4 in AB hearts compared to sham-operated controls. Peptide array experiments showed that CnA binds to the cytoplasmic V-C2 region of syndecan-4 through its autoinhibitory domain. Cell permeable V- or C2-region peptides inactivated or activated NFATc4, respectively, while a C1-derived peptide had no effect, suggesting that syndecan-4 both anchors (V-region) and activates (C2-region) CnA. Moreover, we show that phosphorylation of serine 179 (pS179) is reduced in aortic stenosis patients and in AB murine hearts compared to controls. More CnA was pulled down with non-phosphorylated syndecan-4 than with the phosphorylated form, indicating that reduced pS179 in syndecan-4 is involved in the hypertrophic response. Accordingly, pull-down with pS179 resulted in reduced binding of CnA. Activation of NFATc4 occurred in HEK293 cells transfected with a mutant mimicking minimally phosphorylated S179 (S179A), whereas a mutant mimicking constitutive phosphorylation (S179E) did not. Finally, overexpression of CnA in HEK293 reduces pS179, indicating that CnA regulates its own binding and activation by syndecan-4. Our data indicate that in a pressure-overloaded heart, syndecan-4 activates pro-hypertrophic CnA-NFATc4 signaling, and suggest a crucial role for phosphorylation of syndecan-4 and the syndecan-4-CnA interaction in development of myocardial hypertrophy.
Tuberculosis in hemodialysis patients
Authors: Besma Dhahri, Manel Hdiji, Jihen Ben Ammar, Saloua Azzabi, Walid Feki, Jamel El Ghoul, M. Ali Baccar, Hichem Aouina, Leila El Gharbi, Hend Bouacha
Journal: European Respiratory Journal (2011)

Because of the immunity depression, patients with chronic renal failure undergoing haemodialysis are at increased risk for developing tuberculosis (Tb). The authors propose to review the clinical features of tuberculosis in hemodialysis patients and to underline the diagnostic difficulties.

Tb was seen in seven dialysis patients. Four patients were females, their mean age was 58 years and the mean duration of symptoms was 2,7 months. Revealing symptoms were fever (4cases), cough (2cases), hemoptysis (2cases), asthenia and weight loss (6cases), chest pain (2 cases) and dyspnea (2cases). The Tb localizations were pulmonary in 3 cases, pleural in 3 cases and pleural pulmonary in 1 case. The positive diagnosis represents a real problem: only one patient have a bacteriological confirmation. The diagnosis was posed by anatomopathologic specimen or culture of mycobacterium tuberculosis in 5 cases.

Standard anti TB therapy (isoniasid, rifampin, pyrazinamide, and ethambutol) were performed in 5 patients, two patients were treated by (isoniasid, rifampin, pyrazinamide). IT was success full in four from seven cases, one patient died.

Despite prevention programs, tuberculosis still remains a major international health problem. Prognosis appears to be closely related to therapic precocity, thus specific chemotherapy started sometimes without diagnostic confirmation.
A novel noninvasive diagnostic method for nonalcoholic steatohepatitis using two glycobiomarkers
Authors: Yoshihiro Kamada, Masafumi Ono, Hideyuki Hyogo, Hideki Fujii, Yoshio Sumida, Kojiroh Mori, Saiyu Tanaka, Makoto Yamada, Maaya Akita, Kayo Mizutani, Hironobu Fujii, Akiko Yamamoto, Shinji Takamatsu, Yuichi Yoshida, Yoshito Itoh, Norifumi Kawada, Kazuaki Chayama, Toshiji Saibara, Tetsuo Takehara, Eiji Miyoshi
Journal: Hepatology (2015)

Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus, discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For the diagnosis of NASH, liver biopsy‐proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found that two glycobiomarkers, fucosylated haptoglobin (Fuc‐Hpt) and Mac‐2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc‐Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy‐proven NAFLD patients (training cohort). In addition, we found that the combination of serum Fuc‐Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic analyses, the area under the receiver operating characteristic curve, sensitivity, and specificity of the combination of these two glycobiomarkers were 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis using logistic regression analysis: logit ( p ) = −2.700 + 0.00242 × Fuc‐Hpt + 1.225 × Mac2bp. To validate the prediction model, another 382 biopsy‐proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the area under the receiver operating characteristic curve of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound‐diagnosed NAFLD subjects who received medical health checkups (n = 803). Our model also could predict NAFLD disease severity in this larger population. Conclusion : The combination of serum Fuc‐Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy. (H epatology 2015;62:1433–1443)
SPARC correlation with response to gemcitabine (G) plus nab-paclitaxel (nab-P) in patients with advanced metastatic pancreatic cancer: A phase I/II study
Authors: D. D. Von Hoff, R. Ramanathan, M. Borad, D. Laheru, L. Smith, T. Wood, R. Korn, N. Desai, J. Iglesias, M. Hidalgo
Journal: Journal of Clinical Oncology (2009)

4525 Background: Pancreatic cancer cells and surrounding stroma are known to overexpress SPARC (secreted protein acid rich in cysteine), which is associated with poor clinical outcomes. nab-P, an albumin-bound nanoparticle form of paclitaxel increased tumor accumulation of paclitaxel through binding of albumin to SPARC. This disease specific phase 1 study was designed to evaluate the safety and efficacy of G + nab-P and the correlation of response with tumor SPARC and serum CA19–9 levels. Methods: nab-P doses (100–150 mg/m 2 ) + (G) (1000 mg/m 2 ) were given on days 1, 8, and 15 of a 28-day cycle to pts with metastatic pancreatic adenocarcinoma and with no prior chemotherapy for their metastatic disease. Level 3 SPARC staining by immunohistochemistry was considered positive. Results: 63 pts received treatment. The most common grade 3 and 4 adverse event that occurred in &gt;20% of pts was neutropenia. Nine (18%) pts and 4 (8%) pts had a grade 3/4 event, respectively. Neuropathy was also observed. One combination-associated death due to sepsis occurred at the 150 mg/m 2 nab-P level. Serial PET scans of 53 pts with outside adjudication to date showed 12 (23%) complete responses, 29 (55%) partial responses (PRs) and 4 (8%) stable disease (SD). By RECIST criteria, of the 49 pts evaluable to date, 1(2%) had CR, 12 (24%) had PR, and 20 (41%) had SD. The median survival was 9 months to date. SPARC data were available for 35 pts, of which 10 (29%) were SPARC+ and 25 (71%) were SPARC-. Of these, 27 pts had evaluable response data. Pts that were SPARC+ (8/27) were more likely to be responders (6/8, 75%) than pts who were SPARC- (5/19, 26%), P = 0.03, Fisher's exact test. Median progression-free survival (PFS) increased from 4.8 months for SPARC- pts (22 pts) to 6.2 months for SPARC+ pts (9 pts); however, these data are still immature. Of 45 pts with elevated CA19–9 at baseline, 42 (93%) had maximum decrease of &gt;40% with a median maximum decrease of 92%. Conclusions: The combination of nab-P and G was generally well tolerated and had substantial enough antitumor activity in patients with pancreatic cancer to warrant a phase III clinical trial. SPARC+ status in these patients was associated with higher response rate and longer PFS. [Table: see text]
A Pilot Study into the Prevalence of Ophthalmic Disease in the Indian Population of Southall
Authors: Abdul Rauf, P S Ong, Russell V Pearson, Richard P L Wormald
Journal: Journal of the Royal Society of Medicine (1994)

A pilot study was carried out to determine the prevalence of ophthalmic disease in the Indian community of Southall and to ascertain the best methods applicable for a larger formal study. Three sites were chosen for the study, a Sikh gurdwara, a mosque and a Hindu temple. The subjects were volunteers aged 30 years and over who had visited the appropriate place of worship at least twice in the previous month. A total of 184 subjects were examined. The prevalence of blindness was 2.7% by the World Health Organization (WHO) criteria, while 9.8% had uniocular blindness. The prevalence of glaucoma and ocular hypertension was 2.7% and 7%, respectively. Of the 184 subjects examined, 58% had cataract and 3.8% had age-related maculopathy. The prevalence of visually disabling trachomatous eye disease was 9.7%. The prevalence of diabetes mellitus was 17.9%, and that of hypertension 22.8%. This small study suggests that people with origins from the Indian subcontinent have a higher prevalence of ophthalmic disease than the Caucasian population.
Costs in general practice
Authors: M. Robertson
Journal: BMJ (1996)

EDITOR,—P D P Pharoah and W Hollingworth have calculated the potential costs and benefits of the increased use of statins to prevent deaths from coronary heart disease in a health authority.1 A similar and simpler calculation can be done for the patients of a British general practice.

The results of the west of Scotland coronary prevention study of pravastatin treatment in men with raised cholesterol concentration showed a headline reduction of 32% in cardiovascular mortality and 22% in all cause mortality after …
Lyme borreliosis caused by diverse genospecies of Borrelia burgdorferi sensu lato in northeastern China
Authors: X.-B. Ni, N. Jia, B.-G. Jiang, T. Sun, Y.-C. Zheng, Q.-B. Huo, K. Liu, L. Ma, Q.-M. Zhao, H. Yang, X. Wang, J.-F. Jiang, W.-C. Cao
Journal: Clinical Microbiology and Infection (2014)
Prospective follow-up of novel bone turnover markers in asthmatics exposed to low or high doses of inhaled ciclesonide over 1 year
Authors: William Anderson, Lesley McFarlane, Brian Lipworth
Journal: European Respiratory Journal (2012)

BACKGROUND: There is concern that asthmatics receiving long-term inhaled corticosteroids could develop systemic adverse effects on bone metabolism. We investigated if exposure to inhaled ciclesonide at high vs low doses over 1 year caused any adverse effects on sensitive biomarkers of bone turnover in asthmatics.  METHODS: Post hoc analysis of stored bone marker samples in a subgroup from a prospective, randomised parallel group trial (Lipworth et al. Chest DOI:10.1378/chest.11-1748) where ciclesonide was titrated to control asthma against either mannitol airway hyper-responsiveness (AHR strategy) or control (based on symptoms, reliever use and lung function) over 1 year. 100 mild-moderate asthmatics, 18-65years, with AHR to mannitol challenge had bone marker samples available for analysis. Outcome measures: bone formation (PINP, PIIINP), resorption (ICTP, CTx) and adrenal suppression (overnight urinary cortisol/creatinine: OUCC) at 0 and 12 months.  RESULTS: Mean ciclesonide doses after 12 months were: AHR=507µg/day (n=50); control=202 µg/day (n=50), p  CONCLUSION: Higher doses of inhaled ciclesonide do not adversely affect sensitive markers of bone turnover in asthmatics over 12 months.
Cauliflower Ear
Authors: R Khalak, J K Roberts
Journal: New England Journal of Medicine (1996)

Figure 1. A 16-year-old wrestler had thickened neocartilage in his ear as a result of several untreated auricular hematomas. He presented with a recurrent hematoma that had been drained two days earlier in the emergency department. Panel A shows a hematoma in the superior anthelix and triangular fossa. The drainage site is in the center of the hematoma. After more extensive incision and drainage, with resection of the neocartilage, bolsters were placed on the ear to maintain contact between the perichondrium and the underlying cartilage. One day after surgery, infection with Pseudomonas aeruginosa developed (Panel B). The patient was treated . . .