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1.
Tominaga K Iwakiri R Fujimoto K Fujiwara Y Tanaka M Shimoyama Y Umegaki E Higuchi K Kusano M Arakawa T;GERD Study Group 《Journal of gastroenterology》2012,47(3):284-292
Background
To seek a promising therapeutic regimen for proton pump inhibitor (PPI)-refractory patients with gastroesophageal reflux disease (GERD) after the standard PPI treatment, we compared the efficacies of rikkunshito (a Japanese traditional medication) combined with rabeprazole (RPZ) and a double dose of RPZ in a prospective randomized multicenter trial in Japanese PPI-refractory GERD patients.Methods
One hundred and four patients with GERD symptoms remaining after 4-week treatment with RPZ (10?mg/day) were randomly assigned to 4?weeks of either combination therapy [rikkunshito (7.5?g/day) with a standard dose of RPZ (10?mg/day)] or a double dose of RPZ (20?mg/day). The primary endpoint was the improvement rate, calculated based on the frequency scale for the symptoms of GERD (FSSG) before and after treatment. Subgroup analysis was also performed with respect to each subject??s background factors such as reflux esophagitis (RE)/non-erosive GERD (NERD), age, gender, and body mass index (BMI).Results
Four-week treatment with rikkunshito combined with RPZ significantly decreased the FSSG score from 17.6?±?6.5 to 12.0?±?6.9, similar to the decrease seen on treatment with a double dose of RPZ. Regarding the therapeutic improvement rate, there were also significant effects in both groups. However, in the subgroup analysis based on RE/NERD, the improvement rate of male NERD patients in the rikkunshito group was significantly greater than that of such patients in the other group (P?0.05). In the rikkunshito group, the treatment was more effective in NERD patients with a low BMI than in those with a high BMI (P?0.05).Conclusion
Rikkunshito combined with standard-dose RPZ therapy may be a useful new strategy for PPI-refractory GERD patients. 相似文献2.
Nobuyuki Matsuki Tsuyoshi Fujita Naoya Watanabe Atsushi Sugahara Akihiko Watanabe Tsukasa Ishida Yoshinori Morita Masaru Yoshida Hiromu Kutsumi Takanobu Hayakumo Hidekazu Mukai Takeshi Azuma 《Journal of gastroenterology》2013,48(3):340-349
Background
We aimed to clarify the lifestyle factors associated with erosive esophagitis and non-erosive reflux disease (NERD) in a Japanese population.Methods
Among 886 subjects who underwent health screening, we selected, according to their scores on the FSSG (frequency scale for symptoms of gastroesophageal reflux disease; GERD) questionnaire and the findings of upper gastrointestinal endoscopy, 138 subjects with erosive esophagitis (EE), 148 subjects with NERD (absence of esophagitis, FSSG score ≥8, and acid reflux-related symptoms score ≥4), and 565 control subjects (absence of esophagitis and FSSG score ≤7). We compared clinical characteristics and various lifestyle factors in these three groups.Results
The lifestyle factors significantly associated with NERD compared with findings in the control group were intake of egg (odds ratio [OR] 1.89, 95 % confidence interval [CI] 1.01–3.50), sleep shortage (OR 2.44, 95 % CI 1.54–3.88), and strong psychological stress (OR 1.77, 95 % CI 1.18–2.62). In male subjects, current smoking (OR 2.06, 95 % CI 1.13–3.74; OR 1.87, 95 % CI 1.09–3.20) was a significant risk factor for both NERD and EE. Moreover, alcohol >200 kcal/day (OR 3.99, 95 % CI 1.03–15.55) and intake of a large quantity of food at supper (OR 7.85, 95 % CI 1.66–37.05) were significant risk factors for EE in subjects with hiatal hernia. Intake of a large quantity of food at supper (OR 2.09, 95 % CI 1.06–4.13) was more common in the NERD group than in the EE group.Conclusions
There were differences in the associated lifestyle factors between patients with NERD and those with EE, and there was also a gender-related difference between these groups. 相似文献3.
Purpose
To investigate the effects of soluble FGL2 (sFGL2) secreted by hepatic stellate cells (HSCs) on immune suppression in cirrhotic patients with hepatocellular carcinoma (HCC).Methods
Serum sFGL2 levels were examined by ELISA in 40 patients with HCC, liver cirrhosis (LC) or chronic HBV (CHB) infection. A double staining of the immunofluorescence analysis of α-SMA and FGL2 was performed in two cirrhotic liver specimens. The expression of FGL2 in the LX2 cell line was analyzed by immunofluorescence, Western blot and flow cytometry. T-cells purified from HCC patients using magnetic beads were cultured with LX2 cells at different ratios with anti-CD3-stimulating or FGL2-blocking antibodies. The proliferation index (PI) of CD8 + T cells was assessed by flow cytometry, and the secretion of IFN-γ was measured by ELISA.Results
sFGL2 levels are significantly higher in patients with HCC or LC compared with those with CHB (p = 0.0039/p = 0.0020). Among HCC patients, those with cirrhosis exhibited significantly higher levels of sFGL2 compared with non-cirrhotic individuals (p = 0.0108). The expressions of FGL2 and α-SMA overlapped in HSCs in liver specimens. FGL2 protein secreted by LX2 cells inhibited T-cell proliferation of HCC patients in a dose-dependent manner in vitro. The PI of CD8 + T cells was significantly enhanced following addition of FGL2 antibody to the culture system (LX2/T-cell ratio of 1:10, p = 0.002). The level of IFN-γ in mixed cultures was inversely correlated with the number of HSCs and was reversed by incubation with FGL2 blocking antibody.Conclusion
sFGL2 protein is a novel effector molecule of activated HSCs, which suppresses CD8 + T cell proliferation and interferon-γ production, and it subsequently might contribute to immune suppression during fibrosis and tumorigenesis in the liver. 相似文献4.
Background
Interest in using the nitrogen single-breath washout (N2SBW) test to measure ventilation inhomogeneity and small airway function in COPD patients has grown in recent years. Our aim was to assess the correlation of the measures obtained by the N2SBW test and other pulmonary function parameters with the six-minute walk distance (6MWD), the degree of dyspnea score, and health status in COPD patients.Methods
In this cross-sectional study, 31 patients with COPD were subjected to the N2SBW test, spirometry, whole-body plethysmography, carbon monoxide diffusing capacity measurement, the six-minute walk test, the modified Medical Research Council (mMRC) scale, and the COPD Assessment Test (CAT).Results
We found a strong correlation between the 6MWD and the phase III slope of the nitrogen single-breath washout (Phase III slopeN2SBW) (r = ?0.796; p = 0.0001). We found moderate correlations between the 6MWD and the residual volume (RV) (r = ?0.651; p = 0.0001) and RV/total lung capacity (RV/TLC) (r = ?0.600; p = 0.0004). We also found moderate correlations between the CAT score and Phase III slopeN2SBW (r = 0.728; p = 0.0001), RV (r = 0.646; p = 0.0001) and RV/TLC (r = 0.603; p = 0.0003). There was a significant difference between the mMRC grades for the following variables: Phase III slopeN2SBW (p = 0.0001), RV (p = 0.0001), and smoking history (p = 0.008). Multivariate analysis showed that Phase III slopeN2SBW was the only independent predictor of the 6MWD (R 2 = 0.703; p = 0.0001), CAT score (R 2 = 0.586; p = 0.0001), and mMRC scale (relative risk = 1.14; p = 0.0001).Conclusions
In patients with COPD, our findings suggest that the ventilation inhomogeneity impacts the functional exercise capacity, the degree of dyspnea, and health status. 相似文献5.
Shahinul Alam Utpal Das Gupta Mahbubul Alam Jahangir Kabir Ziaur Rahman Chowdhury A. K. M. Khorshed Alam 《Indian journal of gastroenterology》2014,33(5):452-457
Background
Nonalcoholic fatty liver disease (NAFLD) is considered to be a disease of obese individuals, yet lean patients are increasingly susceptible to have NAFLD. The aim of this study was to evaluate the profile of nonobese patients by comparing with obese NAFLD patients.Methods
We have included 465 patients of NAFLD after exclusion of other diseases, and 220 with elevated alanine aminotransferase (ALT) were biopsied. Patients were biochemically and clinically evaluated: blood pressure, body mass index (BMI), and waist circumference (WC) were recorded for every patient. A BMI ?≥?25 kg/m2 was defined as obese, and those with a BMI of <25 kg/m2 were labeled as nonobese. Histological activity was expressed with NAFLD activity score (NAS).Results
Of 465 cases, 119 (25.6 %) were nonobese. Diabetes was noted in 122 (26.2 %) and hypertension in 122 (26.2 %). Metabolic syndrome was present in 253 (59.7 %), low HDL cholesterol in 228 (64.8 %), hypertriglyceridemia in 297 (73.2 %), and WC above normal in 308 (70.2 %). Males were predominating in the nonobese compared to females in the obese (p?=?0.001). Hypertriglyceridemia and low high-density lipoprotein was similar in the obese and nonobese (76.2 % vs. 72.3 %, p?=?0.5 and 65.2 % vs. 64.6 %, p?=?1.0, respectively). The grades of steatosis, lobular inflammation, ballooning, NAS, and the stage of fibrosis did not also significantly differ between obese and nonobese patients. Nonalcoholic steatohepatitis (NASH) was 53.1 % in nonobese.Conclusion
Nonobese was 25.6 % among NAFLD patients of Bangladesh, and 53.1 % of nonobese NAFLD cases were NASH. Though they were nonobese by BMI grade, they were metabolically similar to obese. Males were predominant in the nonobese, whereas females in the obese. NASH and fibrosis were similar in the obese and nonobese. 相似文献6.
T. Ignatov H. Eggemann S. D. Costa A. Roessner T. Kalinski A. Ignatov 《Journal of cancer research and clinical oncology》2014,140(9):1457-1463
Background
The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum–taxane-based therapy in sporadic ovarian cancer.Patients and methods
BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.Results
BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum–taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32–0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.Conclusions
BRCA1 promoter methylation is predictive for better response to platinum–taxane-based therapy in EOC. 相似文献7.
Sanne de Haas Paul Delmar Aruna T. Bansal Matthieu Moisse David W. Miles Natasha Leighl Bernard Escudier Eric Van Cutsem Peter Carmeliet Stefan J. Scherer Celine Pallaud Diether Lambrechts 《Angiogenesis》2014,17(4):909-920
Background
Despite extensive translational research, no validated biomarkers predictive of bevacizumab treatment outcome have been identified.Methods
We performed a meta-analysis of individual patient data from six randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and gastric cancer to explore the potential relationships between 195 common genetic variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab treatment outcome.Results
The analysis included 1,402 patients (716 bevacizumab-treated and 686 placebo-treated). Twenty variants were associated (P < 0.05) with progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4 variants in EPAS1 survived correction for multiple testing (q < 0.05). Genotype-by-treatment interaction tests revealed that, across these 20 variants, 3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were potentially predictive (P < 0.05), but not resistant to multiple testing (q > 0.05). A weak genotype-by-treatment interaction effect was also observed for rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05). Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci derived from lymphoblastoid cell lines, indicating that they affect the expression levels of their respective gene.Conclusions
This large genetic analysis suggests that variants in VEGF-A, EPAS1, IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment outcome across tumor types. Although these associations did not survive correction for multiple testing in a genotype-by-interaction analysis, they are among the strongest predictive effects reported to date for genetic variants and bevacizumab efficacy. 相似文献8.
9.
Kumar Pallav Toufic Kabbani Sohaib Tariq Rohini Vanga Ciaran P. Kelly Daniel A. Leffler 《Digestive diseases and sciences》2014,59(9):2199-2206
Background
Negative predictive value (NPV) of celiac disease (CD)-related human leukocyte antigens (HLA) DQ2 and DQ8 approaches 100 % in individual patients. However, studies evaluating its exclusionary utility in patient groups are lacking.Aim
We aim to assess the performance of HLA testing when applied to patient groups with varying characteristics and propose evidence-based recommendations for its clinical use.Methods
Demographic and clinical information was recorded in patients undergoing HLA testing. Using predetermined criteria, patients were classified as CD, non-CD, or indeterminate. Diagnostic yield of HLA testing was defined as the percentage of patients in whom CD could be excluded based on negative HLA test.Results
Two hundred and fifty-six patients underwent testing for CD-related HLA DQ2 and DQ8. 102 (100 non-CD, 2 CD) patients tested HLA negative for a 98 % NPV and 39 % diagnostic yield. Diagnostic yield was highest (60 %) in patients with intraepithelial lymphocytosis plus normal IgA tissue transglutaminase antibody (IgA-tTG) and lowest in patients with positive IgA-tTG plus villous atrophy (0 %). CD was diagnosed in two HLA-negative patients, who carried half of DQ2.5 trans genotype.Conclusions
Diagnostic yield of CD-related HLA testing varies widely depending on clinical indication. HLA testing is a practical and valuable test for most patients in whom initial evaluation for CD is inconclusive. A negative HLA result usually obviates the need for further celiac testing including endoscopy and gluten challenge. Rarely, in patients reported as HLA negative, half of HLA DQ2.5 (cis or trans) is sufficient for development of CD. 相似文献10.
Giacomo Mugnai Ruggero Tomei Clementina Dugo Luca Tomasi Giovanni Morani Corrado Vassanelli 《Journal of interventional cardiac electrophysiology》2014,41(1):23-29
Purpose
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive cardiomyopathy characterized by myocardial atrophy and fibro-fatty replacement of the right ventricle (RV) and ventricular tachyarrhythmias in young patients. Our aim was to evaluate clinical course and electronic parameters in patients with implantable cardioverter-defibrillator (ICD) and ARVC, during long-term follow-up.Methods and results
We report on 12 patients with ARVC (mean age 40?±?13 years) who were treated with ICD implantation in our center. Although several RV sites were tested for proper lead positions, the amplitude of R-wave at implantation was quite low (7.4?±?3.0 mV). After a mean follow-up of 91?±?28 months, R-wave amplitude significantly decreased to a mean value of 5.4?±?2.5 mV (p?=?0.03). We also found a noticeable, nearly significant increase in pacing threshold (p?=?0.052) and a moderate increase in defibrillation impedance (p?=?0.07). Six patients (46 %) experienced at least one appropriate ICD therapy; three patients (23 %) experienced inappropriate ICD shocks secondary to the supraventricular tachycardia, T-wave oversensing, and electromagnetic interference.Conclusions
ICD in patients with ARVC has been demonstrated to be feasible and safe. In our case series, we found low R-wave amplitudes at implantation and a significant R-wave decrease during follow-up; a considerable and nearly significant increase in pacing threshold was also observed. These findings may be related to the progressive fibro-fatty replacement of RV myocardium. Multiple sites should be tested in the right ventricle if sensing or pacing values are not optimal, and all the electronic parameters should be carefully monitored throughout the entire follow-up. 相似文献11.
Hong In Yoon Ik Jae Lee Kwang-Hyub Han Jinsil Seong 《Journal of cancer research and clinical oncology》2014,140(9):1595-1605
Aim
To investigate whether image-guided intensity-modulated radiation therapy (IG-IMRT) improves survival in hepatocellular carcinoma (HCC) relative to 3-dimensional conformal radiotherapy (3D-CRT).Methods
Between 2006 and 2011, 187 HCC patients treated with definitive RT were reviewed. Median age was 53(range 51–83). All patients were stage III or IV-A. Concurrent chemoradiation was received by 178 patients (95.2 %). Overall actuarial survival (OS), progression-free survival (PFS), and infield-failure-free survival (IFFS) analyses were performed by Kaplan–Meier method. A Cox proportional hazards model was used for univariate and multivariate analysis. Pearson’s chi-square test or Fisher’s exact test was used to compare patient characteristics and treatment-related toxicity between the groups.Results
Sixty-five patients were treated with IG-IMRT and 122 patients with 3D-CRT. No significant differences were seen between the groups for all patient characteristics. IG-IMRT delivered higher doses than 3D-CRT (median biological effective dose 62.5 vs 53.1 Gy, P < 0.001). IG-IMRT showed significantly higher 3-year OS (33.4 vs 13.5 %, P < 0.001), PFS (11.1 vs 6.0 %, P = 0.004), and IFFS (46.8 vs 28.2 %, P = 0.007) than 3D-CRT. On univariate and multivariate analysis, RT modality was significant prognostic factor for OS (HR 2.18; 95 % CI 1.45–3.25; P < 0.001), PFS (HR 1.64; 95 % CI 1.17–2.29; P = 0.004). There was no significant difference between the two modalities for radiation-induced liver disease (P = 0.716).Conclusion
Our findings suggest that IG-IMRT could be an effective treatment that provides survival benefit without increasing severe toxicity in locally advanced HCC. 相似文献12.
Erica Cohen Roger Bolus Dinesh Khanna Ron D. Hays Lin Chang Gil Y. Melmed Puja Khanna Brennan Spiegel 《Digestive diseases and sciences》2014,59(10):2488-2496
Background
Prior estimates suggest that up to 40 % of the US general population (GP) report symptoms of gastroesophageal reflux disease (GERD). However, symptoms in the GP versus patients seeking care for gastrointestinal (GI) complaints have not been compared. We estimated the prevalence and severity of GERD symptoms in the GP versus GI patients, and identified predictors of GERD severity. We hypothesized that similar to functional GI disorders, psychosocial factors would predict symptom severity in GERD as much, or perhaps more, than care-seeking behavior alone.Methods
We compared the prevalence of heartburn and regurgitation between a sample from the US GP and patients seeking GI specialty care. We compared GERD severity between groups using the NIH PROMIS® GERD scale. We then performed multivariable regression to identify predictors of GERD severity.Results
There was no difference in the prevalence of heartburn between the GP and patient groups (59 vs. 59 %), but regurgitation was more common in patients versus GP (46 vs. 39 %; p = 0.004). In multivariable regression, having high visceral anxiety (p < 0.001) and being divorced or separated (p = 0.006) were associated with higher GERD severity.Conclusions
More than half of a GP sample reports heartburn—higher than previous series and no different from GI patients. Although regurgitation was more prevalent in patients versus the GP, there was no difference in GERD severity between groups after adjusting for other factors; care seeking in GERD appears related to factors beyond symptoms, including visceral anxiety. 相似文献13.
J. C. von Einem V. Heinemann L. Fischer von Weikersthal U. Vehling-Kaiser M. Stauch H. G. Hass T. Decker S. Klein S. Held A. Jung T. Kirchner M. Haas J. Holch M. Michl P. Aubele S. Boeck C. Schulz C. Giessen S. Stintzing D. P. Modest 《Journal of cancer research and clinical oncology》2014,140(9):1607-1614
Purpose
AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients.Patients and methods
Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation.Results
Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed.Conclusion
Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy. 相似文献14.
Kyung Seok Han Sung Joon Hong 《Journal of cancer research and clinical oncology》2014,140(10):1769-1776
Purpose
A transient rise in prostate-specific antigen (PSA) after the initiation of chemotherapy, called as PSA flare, has been frequently reported in patients with castration-resistant prostate cancer (CRPC) but there has been no way to differentiate PSA rises in CRPC. We investigated whether bone-related serum markers differentiate PSA flare from progression in CRPC patients with bone metastasis.Methods
We reviewed CRPC patients with bone metastasis who received systemic chemotherapy from 2002 to 2008. Pretreatment baseline and follow-up data including age, performance score, PSA, Gleason score, alkaline phosphatase (ALP), calcium level, and hemoglobin were evaluated. Pretreatment parameters and follow-up serum parameters after the first cycle of chemotherapy were included in statistical analyses.Results
PSA increased in 38 patients (45.8 %) at the first evaluation after chemotherapy. Among the PSA rises, PSA increased continuously or did not decrease to the stabilization level by the third evaluation in 22 (26.5 %) patients, while PSA decreased to the stabilization or response level by the third evaluation in 16 (19.3 %). PSA flare occurred in 17 (20.5 %). The univariate analyses showed that no baseline parameters were associated with PSA flare, but the initial ALP decrease, changed ALP ratio, and median calcium level were significantly associated with PSA flare (p = 0.001, p = 0.008 and p = 0.012, respectively). Multivariate logistic regression analysis showed that a change in the ALP level is an independent predictive factor for PSA flare (p = 0.017).Conclusions
ALP is a useful biomarker to differentiate PSA flare from early PSA progression during docetaxel chemotherapy in CRPC patients with bone metastasis. 相似文献15.
16.
Maria Francesca Cassarino Antonella Sesta Luca Pagliardini Marco Losa Giovanni Lasio Francesco Cavagnini Francesca Pecori Giraldi 《Pituitary》2014,17(5):464-469
Purpose
It is well known that methylation plays an important role in regulating tissue expression of proopiomelanocortin (POMC) and recent studies have shown that demethylation can occur also in vitro in neuroendocrine tumors. Aim of the present study was to evaluate whether inhibition of methylation modulates POMC expression and ACTH secretion by human corticotrope tumors.Methods
Twenty two ACTH-secreting pituitary tumors were incubated with 5-AZA-2′-deoxycytidine (AZA), an inhibitor of DNA-methyltransferases, with or without 10 nM corticotropin-releasing hormone (CRH). Both dose response (100 nM–10 μM AZA) and time course (4–96 h) experiments were carried out for measurement of ACTH secretion and POMC gene expression.Results
Incubation with AZA increased constitutive POMC expression and ACTH secretion by human corticotrope adenomas. The effect appeared most notable at 24 and 48 h with 1 μM AZA. Incubation with AZA did not exert an additional stimulatory effect on CRH-stimulated POMC and ACTH.Conclusions
The present study shows that AZA increases POMC gene expression and ACTH secretion in human pituitary ACTH-secreting tumors. This can be taken to indicate that mechanisms set into motion by AZA play a role in the regulation of ACTH secretion/POMC expression in tumoral corticotropes and paves the way to further studies in Cushing’s disease. 相似文献17.
Serena Palmieri Valentina Morelli Antonio Stefano Salcuni Cristina Eller-Vainicher Elisa Cairoli Volha V. Zhukouskaya Paolo Beck-Peccoz Alfredo Scillitani Iacopo Chiodini 《Pituitary》2014,17(5):470-476
Purpose
In overt hypercortisolism, growth hormone (GH) secretion is decreased and normalizes after surgery. In subclinical hypercortisolism (SH), GH secretion has been scarcely investigated. We assessed GH reserve in patients with and without SH and, in the former, also after recovery.Methods
We enrolled 24 patients with adrenal adenomas, 12 with SH (SH+, 8 females, 58.3 ± 6.5 years) and 12 without SH (SH?; 11 females, 61.8 ± 10.6 years). SH was diagnosed in the presence of ≥2 out of: 1 mg overnight dexamethasone suppression test >83 nmol/L, urinary free cortisol (UFC) >193 nmol/day and ACTH levels <2.2 pmol/L. GH secretion was assessed by GHRH + Arginine test (GHRH–ARG) and age-adjusted serum IGF-I levels, expressed as SDS (IGF-I SDS). Eight SH+ patients were re-evaluated after the recovery from SH.Results
Age, gender, body mass index (BMI) and IGF-I SDS were comparable between SH+ and SH? patients. After GHRH–ARG the mean GH peak levels (GH-P) and GH response (as Area Under Curve, GH-AUC) were lower in SH+ than in SH? patients (15.2 ± 8.1 vs 44.5 ± 30.9 μg/L, P = 0.004 and 1,418 ± 803 vs 4,028 ± 2,476 μg/L/120 min, P = 0.002, respectively), after adjusting for age and BMI. The GH-AUC and GH-P levels were negatively associated with UFC after adjusting for age and BMI (β = ?0.39, P = 0.02 and β = ?0.4, P = 0.020 respectively). After recovery, GH-P levels and GH-AUC increased as compared to baseline (23.7 ± 16.3 vs 15.8 ± 10.2 μg/L, P = 0.036 and 2,549 ± 1,982 vs 1,618 ± 911 μg/L/120 min, P = 0.012, respectively).Conclusions
GH secretion reserve is decreased in SH patients and increases after the recovery. 相似文献18.
19.
Daniela Jakubowicz Oren Froy Bo Ahrén Mona Boaz Zohar Landau Yosefa Bar-Dayan Tali Ganz Maayan Barnea Julio Wainstein 《Diabetologia》2014,57(9):1807-1811
Aims/hypothesis
Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes.Methods
In a randomised, open-label crossover clinical trial, we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin. These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. Participants were randomised using a coin flip. The primary endpoints of the study were plasma concentrations of glucose, intact GLP-1 and insulin during the 30 min following meal ingestion.Results
In each group, 15 patients were analysed. The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey pre-load with a uniform reduction during both early and late phases. Insulin and C-peptide responses were both significantly higher (by 105% and 43%, respectively) with whey pre-load. Notably, the early insulin response was 96% higher after whey. Similarly, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey pre-load. Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups.Conclusions/interpretation
In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early prandial and late insulin secretion, augmented tGLP-1 and iGLP-1 responses and reduced postprandial glycaemia in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research. 相似文献20.
Yu Sasaki Yoshinobu Okabe Yusuke Ishida Tomoki Taira Makiko Yasumoto Kei Kuraoka Yoshiki Naito Masamichi Nakayama Osamu Tsuruta Michio Sata 《Digestive diseases and sciences》2014,59(9):2314-2319