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1.
Eur Rev Med Pharmacol Sci ; 27(24): 11988-12003, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38164861

ABSTRACT

OBJECTIVE: Febuxostat and benzbromarone are two common drugs for the treatment of gout, but the clinical efficacy of these two drugs is controversial. This meta-analysis aimed to compare the efficacy of febuxostat and benzbromarone in the treatment of gout. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for articles related to febuxostat and benzbromarone in the treatment of gout from inception to January 7, 2023. Titles and abstracts were reviewed in accordance with predesigned inclusion and exclusion criteria, and data were extracted independently. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies, and the continuous variables were expressed as the standard mean square error (SMD) by STATA 16 (Stata Corp., College Station, TX, USA). The sensitivity analysis was conducted by randomly removing a study, and the heterogeneity was analyzed by funnel plots and Egger's test. RESULTS: According to the search strategy, a total of 1,043 publications were retrieved from the three aforementioned databases, of which 45 publications were excluded due to duplication. Fourteen studies remained after screening titles and abstracts, and a total of 7 studies met the inclusion criteria after a comprehensive evaluation of the 14 studies. Meta-analysis showed that the uric acid (UA)-reducing effect of febuxostat is better than that of benzbromarone, while febuxostat showed a better ability to improve the estimated glomerular filtration rate (eGFR) and reduce Cr and blood urea nitrogen (BUN). In terms of hepatotoxicity, benzbromarone was not as potent as febuxostat in increasing alanine transaminase (ALT) and aspartate transaminase (AST), suggesting that benzbromarone has less hepatotoxicity. Moreover, there was no significant difference in the effect on blood lipid levels between the two drugs. CONCLUSIONS: The beneficial effect of febuxostat on renal function-related indexes such as the eGFR, Cr and BUN is significant, while benzbromarone is more effective in reducing UA and has relatively less hepatotoxicity. The specific efficacy of the two drugs needs to be confirmed by further research.


Subject(s)
Benzbromarone , Febuxostat , Gout Suppressants , Gout , Uricosuric Agents , Humans , Allopurinol/therapeutic use , Benzbromarone/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , China , Febuxostat/therapeutic use , Gout/drug therapy , Gout Suppressants/therapeutic use , Hyperuricemia , Treatment Outcome , Uric Acid , Uricosuric Agents/therapeutic use
2.
Eur Rev Med Pharmacol Sci ; 24(10): 5592-5603, 2020 05.
Article in English | MEDLINE | ID: mdl-32495894

ABSTRACT

OBJECTIVE: Lipopolysaccharide (LPS)-induced inflammation and dysfunction in the kidney may be the major risk factors for subsequent acute kidney injury (AKI). Previous studies have reported that up-regulation of notch receptor 3 (NOTCH3) expression is accompanied with renal epithelium and podocyte damage. Herein, we aimed to investigate whether NOTCH3 was involved in lipopolysaccharide (LPS)-induced AKI and renal cell dysfunction. MATERIALS AND METHODS: Septic mice were established using LPS (20 mg/kg) intraperitoneally. mRNA and protein expression in the kidney and renal cell was performed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. Cell counting kit-8 (CCK8) and flow cytometry were used to measure cell viability and apoptosis, respectively. Bioinformatics algorithm and Luciferase reporter gene assay were performed to validate whether NOTCH3 was a direct target of miR-201-5p. RESULTS: Up-regulation of NOTCH3 and down-regulation of miR-201-5p were observed in the kidney of LPS-induced septic mice. LPS-stimulated TCMK-1 and MPC5 cells led to an increase in NOTCH3 and a decrease in miR-201-5p expression levels. Bioinformatics algorithm and experimental measurements validated that NOTCH3 was a direct target of miR-201-5p. Overexpression of miR-201-5p protected against LPS-induced renal cell growth inhibition, apoptosis and inflammatory response via the suppression of toll-like receptor 4 (TLR4)/NOTCH3 signaling pathway. CONCLUSIONS: The novel role of miR-201-5p via the inhibition of LPS-activated TLR4/NOTCH3 might provide a potential therapeutic strategy for the treatment of LPS-induced AKI.


Subject(s)
Epithelial Cells/metabolism , MicroRNAs/metabolism , Receptor, Notch3/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Cells, Cultured , Epithelial Cells/pathology , Lipopolysaccharides , Male , Mice , Mice, Inbred C57BL , MicroRNAs/genetics , Receptor, Notch3/genetics
3.
J Hosp Infect ; 101(1): 69-75, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30026006

ABSTRACT

BACKGROUND: Vancomycin-resistant enterococcus (VRE) causes 4% of all healthcare-associated infections in the USA. The process by which the local hospital milieu contributes to VRE acquisition is not fully understood. AIM: To determine the importance of specific factors within the local hospital environment for healthcare-associated VRE acquisition. METHODS: This retrospective cohort study included patients admitted to six intensive care units at an academic medical centre from January 2012 to December 2016 with negative rectal VRE cultures on admission. VRE acquisition was defined as a positive surveillance swab performed at any time after the initial negative swab during the index hospitalization. The exposures of interest were VRE colonization pressure, VRE importation pressure, and use of vancomycin. Multivariable Cox proportional hazards modelling was performed, with patients followed until VRE acquisition, death, or for up to 30 days. FINDINGS: Of 8485 patients who were initially VRE negative, 161 patients acquired VRE. On univariate analysis, patients with VRE acquisition were more likely to have received vancomycin, to have had a neighbouring patient who received vancomycin, to have high VRE importation pressure, or to have high VRE colonization pressure. On multivariable analysis, only high VRE colonization pressure was an independent predictor of VRE acquisition (adjusted hazard ratio: 1.79; 95% confidence interval: 1.19-2.70). CONCLUSION: VRE colonization pressure was the most important risk factor for healthcare-associated VRE acquisition, regardless of VRE importation pressure. Interventions seeking to reduce VRE acquisition should focus on minimizing transmission between patients with known VRE and the local hospital environment.


Subject(s)
Cross Infection/epidemiology , Cross Infection/microbiology , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Vancomycin-Resistant Enterococci/isolation & purification , Academic Medical Centers , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Cross Infection/transmission , Disease Transmission, Infectious , Drug Utilization , Female , Gram-Positive Bacterial Infections/transmission , Humans , Intensive Care Units , Male , Middle Aged , Prevalence , Rectum/microbiology , Retrospective Studies , United States/epidemiology , Vancomycin/therapeutic use , Young Adult
4.
Dis Esophagus ; 31(5)2018 May 01.
Article in English | MEDLINE | ID: mdl-29293904

ABSTRACT

Eosinophilic esophagitis is characterized by eosinophil inflammation restricted to the esophagus and the resulting symptoms of esophageal dysfunction. Critical to the diagnosis of eosinophilic esophagitis is a trial of proton pump inhibitor therapy to exclude alternative causes of esophageal eosinophilia such as proton pump inhibitor-responsive esophageal eosinophilia. While consensus guidelines recommend a proton pump inhibitor trial prior to diagnosis, little is known about its implementation in clinical practice. The primary aim of this study is to assess the frequency of proton pump inhibitor trial prior to the diagnosis of eosinophilic esophagitis in community practice. The secondary aim is to assess the frequency of other treatments for eosinophilic esophagitis, including topical steroids and/or dietary therapy, in patients who did not undergo a proton pump inhibitor trial prior to diagnosis or who had an alternative diagnosis to eosinophilic esophagitis upon completed workup. We conducted a single-center, case series of patients referred to the Hospital of the University of Pennsylvania for eosinophilic esophagitis management between 2010 and 2015. This case series consisted of 125 patients who were referred from community practitioners with a presumptive diagnosis of eosinophilic esophagitis. Upon review, 90 out of 125 (72%) patients had not had a proton pump inhibitor trial or esophageal pH testing prior to the diagnosis of eosinophilic esophagitis being made. Of these patients, 77.8% (70/90) had already received either topical steroid or dietary therapy for presumed eosinophilic esophagitis. Of the 125 patients initially diagnosed with eosinophilic esophagitis, 32 (25.6%) were found to have an alternative diagnosis, and 79.2% of this subset of patients (25/32) had previously received topical steroid or dietary therapy. This study demonstrates that a substantial number of patients with presumed eosinophilic esophagitis have not had a proton pump inhibitor trial prior to diagnosis in community practice. This led to the misclassification of patients and potentially to the use of less optimal medical therapies in a substantial number of these patients.


Subject(s)
Diagnostic Errors , Eosinophilic Esophagitis , Proton Pump Inhibitors/administration & dosage , Adult , Diagnosis, Differential , Diagnostic Errors/adverse effects , Diagnostic Errors/prevention & control , Diagnostic Errors/statistics & numerical data , Eosinophilic Esophagitis/diagnosis , Eosinophilic Esophagitis/epidemiology , Eosinophilic Esophagitis/therapy , Female , Humans , Male , Middle Aged , Patient Selection , Pennsylvania/epidemiology , Retrospective Studies , Time-to-Treatment
5.
Am J Transplant ; 18(1): 207-215, 2018 01.
Article in English | MEDLINE | ID: mdl-28640504

ABSTRACT

Cardiovascular disease is a leading cause of death among liver transplant (LT) recipients. With a rising burden of posttransplantation metabolic disease, increases in cardiovascular-related morbidity and mortality may reduce life expectancy after LT. It is unknown if the risk of long-term major cardiovascular events (MCEs) differs among LT recipients with varying diabetic states. We performed a retrospective cohort study of LT recipients from 2003 through 2013 to compare the incidence of MCEs among patients (1) without diabetes, (2) with pretransplantation diabetes, (3) with de novo transient posttransplantation diabetes, and (4) with de novo sustained posttransplantation diabetes. We analyzed 994 eligible patients (39% without diabetes, 24% with pretransplantation diabetes, 16% with transient posttransplantation diabetes, and 20% with sustained posttransplantation diabetes). Median follow-up was 54.7 months. Overall, 12% of patients experienced a MCE. After adjustment for demographic and clinical variables, sustained posttransplantation diabetes was the only state associated with a significantly increased risk of MCEs (subdistribution hazard ratio 1.95, 95% confidence interval 1.20-3.18). Patients with sustained posttransplantation diabetes mellitus had a 13% and 27% cumulative incidence of MCEs at 5 and 10 years, respectively. While pretransplantation diabetes has traditionally been associated with cardiovascular disease, the long-term risk of MCEs is greatest in LT recipients with sustained posttransplantation diabetes mellitus.


Subject(s)
Cardiovascular Diseases/etiology , Diabetes Mellitus/etiology , Graft Rejection/etiology , Liver Transplantation/adverse effects , Postoperative Complications , Cardiovascular Diseases/epidemiology , Diabetes Mellitus/epidemiology , Female , Follow-Up Studies , Graft Rejection/epidemiology , Graft Survival , Humans , Incidence , Male , Middle Aged , Philadelphia/epidemiology , Prognosis , Retrospective Studies , Risk Factors
6.
Article in English | MEDLINE | ID: mdl-28252230

ABSTRACT

Depression might be associated with shorter disease specific survival. Selective serotonin reuptake inhibitors (SSRIs) were previously reported to increase the risk of certain malignancies. We aimed to evaluate the impact of SSRIs on cancer mortality. Five retrospective cohort studies were conducted in a UK population-representative database that included all individuals with an incident diagnosis of melanoma, breast, prostate lung and colorectal cancer. The primary exposure of interest was continuous use of SSRIs with past use as the comparison reference. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). The study included 5,591 newly diagnosed cancer patients. Continuous SSRI use was associated with lower survival compared to past users for melanoma, breast, prostate, lung and colorectal cancers with HRs for the risk of death of 2.02 (95% CI 1.24-3.28), 1.91 (95% CI 1.53-2.38), 1.79 (95% CI 1.38-2.33), 1.44 (95% CI 1.19-1.75) and 1.51 (95% CI 1.21-1.72) respectively. The incidence of death during the first 2 years following cancer diagnosis associated with continuous SSRI use were elevated for breast (1.72, 95% CI 1.30-2.27), prostate (1.64, 95% CI 1.20-2.24) and lung cancers (1.45, 95% CI 1.26-1.66). In conclusion, continuous use of SSRIs might be associated with lower survival in cancer patients.


Subject(s)
Depressive Disorder/drug therapy , Neoplasms/mortality , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adult , Aged , Aged, 80 and over , Depressive Disorder/etiology , Female , Humans , Incidence , Male , Middle Aged , Neoplasms/psychology , Retrospective Studies , Survival Analysis
7.
Dis Esophagus ; 30(6): 1-6, 2017 Jun 01.
Article in English | MEDLINE | ID: mdl-28475741

ABSTRACT

Esophagogastric junction outflow obstruction, characterized by preserved peristalsis in conjunction with an elevated integrated relaxation pressure, can result from specific anatomic variants or may represent achalasia in evolution. There is limited information on the clinical significance of this diagnosis. The aim of this study is to describe the clinical characteristics and outcomes in our cohort of patients with esophagogastric junction outflow obstruction.Consecutive adult patients who had undergone high-resolution esophageal manometry between February 2013 and November 2015 with a diagnosis of esophagogastric junction outflow obstruction were identified. Electronic medical records were reviewed to determine: (1) secondary causes of esophagogastric junction outflow obstruction; (2) treatment; and (3) natural history. Improvement in symptoms noted during follow-up evaluation was considered to be a favorable outcome. Worsening of symptoms or no change in symptoms was considered to be an unfavorable outcome.Of 874 manometries performed during this time period, 83 met the criteria for esophagogastric junction outflow obstruction. Of these patients, 11 had secondary causes: paraesophageal hernia (4), Nissen fundoplication (2), esophageal stricture (3), prior laparoscopic band placement (1), and diverticulum (1). All of these secondary causes were identified by barium esophagram. The remaining 72 patients were categorized as idiopathic esophagogastric junction outflow obstruction. Two patients developed type II achalasia on follow-up. An additional two patients had no symptoms as testing was performed for preoperative evaluation prior to bariatric surgery, leaving 68 patients for symptom follow-up analysis. Of these, 19 had a favorable outcome, 18 had an unfavorable outcome, and 31 were lost to follow-up. Of those with a favorable outcome, 6 patients underwent treatment: medication (3), botulinum toxin injection followed by laparoscopic Heller myotomy (1), botulinum toxin injection and medication (1), and bougie dilation (1). Of the 18 patients with an unfavorable outcome, 6 patients underwent treatment: botulinum toxin injection (5) and medication (1). Computed tomography scan or endoscopic ultrasound was performed in 40% of patients with available follow-up and none of these studies revealed secondary causes. The overall median follow-up time was 5 months.Esophagogastric outflow obstruction is a manometric finding of unclear significance. Secondary causes should first be excluded with structural studies. The evolution of esophagogastric junction outflow obstruction to achalasia is rare. Symptoms in patients with esophagogastric junction outflow obstruction do not always require treatment and treatment response is variable. The challenge in managing these patients lies in distinguishing which patients will need intervention. Further studies are needed for consideration of subgrouping this disease or modifying the categorization into clinically relevant entities.


Subject(s)
Esophageal Diseases/physiopathology , Esophagogastric Junction/physiopathology , Manometry/methods , Aged , Disease Progression , Esophageal Achalasia/etiology , Esophageal Achalasia/physiopathology , Esophageal Diseases/diagnostic imaging , Esophageal Diseases/etiology , Esophagogastric Junction/diagnostic imaging , Female , Humans , Male , Middle Aged , Peristalsis/physiology , Pressure , Retrospective Studies
8.
Osteoporos Int ; 26(10): 2501-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-25986385

ABSTRACT

UNLABELLED: Proton pump inhibitors (PPIs) are associated with risk for fracture in osteoporotic adults. In this population-based study, we found a significant association between PPIs and fracture in young adults, with evidence of a dose-response effect. Young adults who use PPIs should be cautioned regarding risk for fracture. INTRODUCTION: Proton pump inhibitors (PPIs) are associated with fracture in adults with osteoporosis. Because PPI therapy may interfere with bone accrual and attainment of peak bone mineral density, we studied the association between use of PPIs and fracture in children and young adults. METHODS: We conducted a population-based, case-control study nested within records from general medical practices from 1994 to 2013. Participants were 4-29 years old with ≥ 1 year of follow-up who lacked chronic conditions associated with use of long-term acid suppression. Cases of fracture were defined as the first incident fracture at any site. Using incidence density sampling, cases were matched with up to five controls by age, sex, medical practice, and start of follow-up. PPI exposure was defined as 180 or more cumulative doses of PPIs. Conditional logistic regression was used to estimate the odds ratio and confidence interval for use of PPIs and fracture. RESULTS: We identified 124,799 cases and 605,643 controls. The adjusted odds ratio for the risk of fracture associated with PPI exposure was 1.13 (95% CI 0.92 to 1.39) among children aged < 18 years old and 1.39 (95% CI 1.26 to 1.53) among young adults aged 18-29 years old. In young adults but not children, we observed a dose-response effect with increased total exposure to PPIs (p for trend <0.001). CONCLUSIONS: PPI use was associated with fracture in young adults, but overall evidence did not support a PPI-fracture relationship in children. Young adults who use PPIs should be cautioned regarding potentially increased risk for fracture, even if they lack traditional fracture risk factors.


Subject(s)
Osteoporotic Fractures/chemically induced , Proton Pump Inhibitors/adverse effects , Adolescent , Adult , Age Factors , Case-Control Studies , Child , Child, Preschool , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Histamine H2 Antagonists/adverse effects , Humans , Male , Osteoporotic Fractures/epidemiology , Proton Pump Inhibitors/administration & dosage , United Kingdom/epidemiology , Young Adult
9.
Dis Esophagus ; 28(6): 538-46, 2015.
Article in English | MEDLINE | ID: mdl-24849246

ABSTRACT

Considerable variability exists in adherence to practice guidelines for Barrett's esophagus (BE). Rapid advances in management approaches to BE led to a new American Gastroenterological Association (AGA) medical position statement in 2011. Our aim was to assess how well members of the AGA Clinical Practice section adhered to these guidelines. A self-administered survey incorporating questions on diagnostic criteria, cancer risk estimates, screening, surveillance, and therapeutics for BE was distributed electronically to 5850 North American members of the AGA Clinical Practice section. The response rate was 470 of 2040 opened e-mails (23%). Intestinal metaplasia was required for diagnosis of BE by 90%, but the Prague classification was used by only 53% of those aware of it. The annual risk of progression to esophageal adenocarcinoma was reported as 0.1-0.5% by 76%. Screening practices were variable, with 35% screening all patients with chronic gastroesophageal reflux disease and 15% repeating endoscopy in patients with gastroesophageal reflux disease following a negative screening. Surveillance guidelines were followed by 79% for nondysplastic BE and 86% for low-grade dysplasia, with expert pathology confirmation of dysplasia reported by 86%. Proton pump inhibitor dosing was variable, with 18% administering twice-daily doses and 30% titrating dose to symptoms. Ablation therapy was recommended by 6% for nondysplastic BE, 38% for low-grade dysplasia, and 52% for high-grade dysplasia. There is satisfactory adherence to the new AGA guidelines with respect to diagnosis, cancer risk estimates, and surveillance intervals in a select group of respondents. However, adherence continues to be variable in the use of the Prague classification, screening, and dosing of antisecretory therapy. Use of ablation therapy increases with grade of dysplasia. The reason for continued variability in adherence to BE practice guidelines remains unclear, and more evidence-based guidance is required to enhance clinical practice.


Subject(s)
Barrett Esophagus/diagnosis , Gastroenterology/standards , Guideline Adherence/statistics & numerical data , Practice Guidelines as Topic/standards , Practice Patterns, Physicians'/statistics & numerical data , Adult , Barrett Esophagus/classification , Female , Humans , Male , Middle Aged , Practice Patterns, Physicians'/standards , Societies, Medical , Surveys and Questionnaires , United States
10.
Aliment Pharmacol Ther ; 40(7): 843-53, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25123489

ABSTRACT

BACKGROUND: A large proportion of US Medicare beneficiaries undergo earlier-than-recommended follow-up colonoscopies after negative screening colonoscopy. Such practice entails substantial cost and added risk. AIMS: To compare the risk of colorectal cancer (CRC) associated with varying follow-up colonoscopy intervals following a negative colonoscopy, and to determine whether the potential benefit of a shorter colonoscopy follow-up interval would differ by gender. METHODS: We conducted a weighted cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database (1991-2006) among 932,370 Medicare enrollees who are representative of the entire US elderly population. We compared the cumulative incidence of CRC among patients who underwent follow-up colonoscopies at different intervals following a negative colonoscopy. The primary outcome was incident CRC. RESULTS: The eligible study cohort (n = 480,864) included 106,924 patients who underwent ≥1 colonoscopy. Men were more likely to require polypectomy during their initial colonoscopy than women. Compared to the recommended 9-10 year follow-up colonoscopy interval, an interval of 5-6 years was associated with the largest CRC cumulative risk reduction [i.e. 0.17% (95% CI: 0.009-0.32%)]. The magnitude of risk reduction associated with shorter colonoscopy follow-up intervals was not significantly different between men and women. CONCLUSIONS: Among elderly individuals who undergo a negative colonoscopy, the magnitude of reduction in the cumulative CRC risk afforded by earlier-than-recommended follow-up colonoscopy is quite small, and probably cannot justify the risk and cost of increased colonoscopy frequency. In addition, there are insufficient differences between men and women to warrant gender-specific recommendations.


Subject(s)
Colonoscopy , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Incidence , Male , Mass Screening , Medicare , United States
11.
Transplant Proc ; 46(1): 21-5, 2014.
Article in English | MEDLINE | ID: mdl-24507020

ABSTRACT

Lymphoproliferative disease after hematopoietic stem cell transplantation is a serious and life-threatening disease. CD8(+) T lymphocytes play a key role in the control of viral diseases and some tumors. Adoptive immunotherapy has been shown to be effective in controlling and preventing some virus-related diseases in transplant recipients. However, the ex vivo production of cells for adoptive transfer is labor-intensive and expensive. To simplify the culture procedures of Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes, we explored a novel method, a rapid expansion protocol, that only used recombinant human interleukin to initiate the growth of clinical-grade EBV-specific T cells. After restimulation with EBV peptides principally from latent antigens and immediate/early antigens, the CD8(+) cells obtained could produce cytokines that had cytotoxic activity against target cells. This method provides a new possibility for the treatment of life-threatening EBV-associated malignancies.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Epstein-Barr Virus Infections/immunology , Herpesvirus 4, Human/metabolism , Adoptive Transfer/methods , B-Lymphocytes/cytology , Cell Proliferation , Cytokines/metabolism , Epitopes/immunology , HLA Antigens/immunology , Humans , Immunophenotyping , Immunotherapy/methods , Lysosomal-Associated Membrane Protein 1/metabolism , Stem Cell Transplantation , T-Lymphocytes/cytology , T-Lymphocytes/immunology , T-Lymphocytes, Cytotoxic/immunology
12.
Cancer Biother Radiopharm ; 28(5): 406-14, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23484810

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignant gastroenterological cancers over the world. α-fetoprotein (AFP) is an oncofetal protein produced during HCC development that could generate weaker and less reproducible antitumor protection, and it may serve as a target for immunotherapy. Therefore, it is imperative to enhance its immunogenicity and develop therapeutic vaccines to eliminate AFP-expressing tumors. In this study, by way of glutaraldehyde cross-linking, we constructed a potential therapeutic protein vaccine, glycoprotein 96 (gp96)/AFP. Our results demonstrated that AFP and gp96 synergistically exhibited significant increase in AFP-specific CD8⁺ T-cell responses and impressive cytotoxic antitumor effect against AFP-expressing tumors. Priming mice with the reconstructed vaccine, we elicited robust strong protective immunity. Our study suggests that tumor vaccine by cross-linking tumor antigen and gp96 is a promising approach to cancer therapy.


Subject(s)
Cancer Vaccines/therapeutic use , Carcinoma, Hepatocellular/therapy , Immunity, Cellular/immunology , Immunotherapy , Liver Neoplasms/therapy , Membrane Glycoproteins/metabolism , alpha-Fetoproteins/metabolism , Animals , Blotting, Western , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Liver Neoplasms/immunology , Liver Neoplasms/metabolism , Membrane Glycoproteins/immunology , Mice , Mice, Inbred BALB C , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes, Cytotoxic/immunology , Vaccination , alpha-Fetoproteins/immunology
13.
Aliment Pharmacol Ther ; 37(1): 114-21, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23121227

ABSTRACT

BACKGROUND: Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition affecting both children and adults. Little is known about the natural history of EoE in the transition from childhood into adulthood. AIM: To determine the prevalence of EoE symptoms and impact of EoE on quality of life among adults diagnosed with EoE during childhood. METHODS: This is a cross-sectional study of EoE patients from the Children's Hospital of Philadelphia EoE registry. Patients ≥18 years diagnosed with EoE during childhood were administered validated dysphagia [Mayo Dysphagia Questionnaire (MDQ)-30] and Quality of Life (PAGI-QOL) questionnaires. Ongoing EoE treatments were ascertained. RESULTS: A total of 140 EoE patients ≥18 years were identified; 53 completed all questions. Only 6 (11%) subjects had positive (n = 2) or indeterminate (n = 4) dysphagia scores. However, of 47 patients with negative scores, 18 (37%) reported ongoing difficulty swallowing. The mean PAGI-QOL score was 4.58/5. The dietary dimension score was 3.73/5. Current pharmacological EoE treatments were topical steroids (3/53) and interleukin-5 antagonists (3/53). Additionally, 26/53 (49%) were on PPI therapy and 40/53 (76%) were following allergy directed diets. CONCLUSIONS: The majority of young adults diagnosed with EoE during childhood continue to require pharmacological treatment and/or dietary modification for EoE. A substantial proportion of this population experiences ongoing swallowing difficulties that a standard dysphagia questionnaire fails to capture. Dietary quality of life, but not total quality of life, appears to be adversely affected. These data suggest that EoE diagnosed during childhood remains a significant medical issue during early adulthood, and that better EoE symptom measurement instruments are needed.


Subject(s)
Eosinophilic Esophagitis/diagnosis , Quality of Life , Adolescent , Age Factors , Child , Child, Preschool , Cross-Sectional Studies , Deglutition Disorders/diagnosis , Deglutition Disorders/physiopathology , Eosinophilic Esophagitis/drug therapy , Eosinophilic Esophagitis/physiopathology , Female , Glucocorticoids/therapeutic use , Humans , Male , Proton Pump Inhibitors/therapeutic use , Severity of Illness Index , Surveys and Questionnaires , Time Factors , Young Adult
14.
Phys Rev Lett ; 111(26): 267001, 2013 Dec 27.
Article in English | MEDLINE | ID: mdl-24483810

ABSTRACT

Using electronic Raman spectroscopy, we report direct measurements of charge nematic fluctuations in the tetragonal phase of strain-free Ba(Fe(1-x)Co(x))2As2 single crystals. The strong enhancement of the Raman response at low temperatures unveils an underlying charge nematic state that extends to superconducting compositions and which has hitherto remained unnoticed. Comparison between the extracted charge nematic susceptibility and the elastic modulus allows us to disentangle the charge contribution to the nematic instability, and to show that charge nematic fluctuations are weakly coupled to the lattice.

15.
Int J Clin Pract ; 66(6): 582-91, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22607510

ABSTRACT

Proton pump inhibitors are highly effective acid suppressants with decades of use highlighting positive outcomes in millions of patients worldwide, and they offer minimal risk of adverse events. PPIs are considered overutilised when prescribed without an appropriate indication, when patients are left on them 'indefinitely' without appropriate indications and when they are continued after being utilised for most cases of hospital SUP. While several adverse outcomes have been linked to PPI therapy, most data are from retrospective observational studies that may be subject to confounding and bias.


Subject(s)
Gastroesophageal Reflux/drug therapy , Proton Pump Inhibitors/therapeutic use , Ambulatory Care , Epidemiologic Methods , Forecasting , Gastric Acid/metabolism , Gastric Acid/physiology , Gastroesophageal Reflux/metabolism , Health Services Misuse , Humans , Long-Term Care , Patient Safety , Proton Pump Inhibitors/adverse effects , Proton Pump Inhibitors/pharmacology , Stomach Ulcer/drug therapy , Stomach Ulcer/psychology , Stress, Psychological/complications
16.
Br J Cancer ; 103(7): 961-9, 2010 Sep 28.
Article in English | MEDLINE | ID: mdl-20808312

ABSTRACT

BACKGROUND: Our recent study observed that the expression of ubiquitin D (UBD), a member of ubiquitin-like modifier family, was upregulated in colon cancer parenchymal cells. The present study further investigated the clinical signicance of UBD in colon cancer. METHODS: Using quantitative PCR, tissue microarray (TMA), western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and protein levels in tumour tissues from patients with colon cancer at different stages and in paired adjacent normal epithelium. RESULTS: Immunohistochemical detection of UBD on a TMA containing 203 paired specimens showed that increased cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph node metastasis, distant metastasis, tumour histologic grade, advanced clinical stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a significantly higher disease recurrence rate and poorer survival than patients with UBD-negative tumours after the radical surgery. Stratification analysis according to tumour stage revealed UBD as an independent predictor for tumour recurrence in patients with stage II and III tumours. CONCLUSION: UBD may contribute to the progression of colon carcinogenesis and function as a novel prognostic indicator of forecasting recurrence of stage II and III patients after curative operations.


Subject(s)
Biomarkers, Tumor/metabolism , Colonic Neoplasms/metabolism , Ubiquitins/metabolism , Aged , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Disease Progression , Disease-Free Survival , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Prognosis , Protein Array Analysis , Recurrence
17.
Reprod Domest Anim ; 45(4): 694-8, 2010 Aug.
Article in English | MEDLINE | ID: mdl-19210666

ABSTRACT

The aim of this study was to detect the effects of different combinations of cryoprotectants with different equilibrium time on the mouse ovarian tissue during vitrification. Ovarian tissue of mice was vitrified-thawed. Mice (n = 80) were randomly assigned to treatment groups according to different vitrification solutions [I: 20% (v/v) ethylene glycol (EG) + 20% (v/v) Dimethylsulfoxde (DMSO), II: 20% (v/v) EG + 20% (v/v) PROH, III: 20% (v/v) PROH + 20% (v/v) DMSO] and different lengths of equilibrium time (a: 15 min, b: 30 min, c: 45 min). The serum levels of estradiol, the follicular density and the percentage of cells expressing Proliferating-cell nuclear antigen (PCNA) of grafts in Group IIb were the highest in all these treatment groups. In addition, the serum levels of estradiol, the follicular density and the percentage of cells expressing PCNA of grafts in Group Ib were significantly higher than those in Group Ia and Group Ic, while the serum levels of estradiol, the follicular density and the percentage of cells expressing PCNA of grafts in Group IIIb were significantly higher than those in Group IIIa and Group IIIc. In conclusion, vitrification solution [20% (v/v) EG + 20% (v/v) PROH] with equilibrium time of 30 min is optimal selection for vitrifying mouse ovarian tissue.


Subject(s)
Ovary/physiology , Tissue Preservation/methods , Vitrification , Animals , Estradiol/metabolism , Female , Mice , Mice, Inbred ICR , Ovary/transplantation , Random Allocation
18.
Int J Gynecol Cancer ; 16(5): 1868-72, 2006.
Article in English | MEDLINE | ID: mdl-17009984

ABSTRACT

Tumor suppressor in lung cancer 1 (TSLC1) is a tumor suppressor gene in non-small cell lung cancer, and loss of TSLC1 gene expression has been observed in a number of epithelial carcinomas and cancer-derived cell lines. We analyzed TSLC1 gene expression by real-time reverse transcription-polymerase chain reaction in 39 invasive cervical carcinomas, 34 cervical intraepithelial neoplasia (CIN) IIIs, 35 CIN IIs, 32 CIN I, 36 inflammation cervical tissues, and 30 normal cervix samples. Loss of TSLC1 gene expression was observed in 30 of 39 (77%) cervical carcinomas, 25 of 34 (73%) CIN IIIs, 9 of 35 (26%) CIN IIs, and 7 of 32 (22%) CIN Is but was not found in inflammation and normal cervix samples. Compared to normal cervical tissue, loss of TSLC1 gene was significantly high in CIN IIIs and cervical cancer (P = 0.00). Moreover, loss of TSLC1 gene expression is observed at a significantly higher frequency in CIN IIIs and cervical cancers than in CIN IIs (P < 0.05). The results show that loss of TSLC1 gene expression is an early event in cervical carcinogenesis and often accompanies invasive cervical cancers.


Subject(s)
Carcinoma/metabolism , Cervix Uteri/metabolism , Immunoglobulins/metabolism , Membrane Proteins/metabolism , Tumor Suppressor Proteins/metabolism , Uterine Cervical Neoplasms/metabolism , Uterine Cervicitis/metabolism , Carcinoma/virology , Cell Adhesion Molecule-1 , Cell Adhesion Molecules , Female , Gene Expression Regulation, Neoplastic , Humans , Papillomaviridae , Papillomavirus Infections/metabolism , Polymerase Chain Reaction , Uterine Cervical Neoplasms/virology
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