共查询到20条相似文献，搜索用时 109 毫秒
1.
Ingeborg A. Brouwer Johanna M. Geleijnse Veronique M. Klaasen Liesbeth A. Smit Erik J. Giltay Janette de Goede Annemieke C. Heijboer Daan Kromhout Martijn B. Katan 《PloS one》2013,8(12)
Background
Alpha linolenic acid (ALA) is the major omega-3 fatty acid in the diet. Evidence on health effects of ALA is not conclusive, but some observational studies found an increased risk of prostate cancer with higher intake of ALA. We examined the effect of ALA supplementation on serum concentrations of prostate-specific antigen (PSA), a biomarker for prostate cancer.Methods
The Alpha Omega Trial (ClinicalTrials.gov Identifier: NCT00127452) was a double-blind, placebo-controlled trial of ALA and the fish fatty acids eicosapentanoic acid (EPA) and docosahexanoic acid (DHA) on the recurrence of cardiovascular disease, using a 2×2 factorial design. Blood was collected at the start and the end of the intervention period. The present analysis included 1622 patients with a history of a myocardial infarction, aged 60–80 years with an initial PSA concentration <4 ng/mL. They received either 2 g per day of ALA or placebo in margarine spreads for 40 months. T-tests and logistic regression were used to assess the effects of ALA supplementation on changes in serum PSA (both continuously and as a dichotomous outcome, cut-off point: >4 ng/mL).Findings
Mean serum PSA increased by 0.42 ng/mL on placebo (n = 815) and by 0.52 ng/mL on ALA (n = 807), a difference of 0.10 (95% confidence interval: −0.02 to 0.22) ng/mL (P = 0·12). The odds ratio for PSA rising above 4 ng/mL on ALA versus placebo was 1.15 (95% CI: 0.84–1.58).Interpretation
An additional amount of 2 g of ALA per day increased PSA by 0.10 ng/mL, but the confidence interval ranged from −0.02 to 0.22 ng/mL and included no effect. Therefore, more studies are needed to establish whether or not ALA intake has a clinically significant effect on PSA or prostate cancer.Trial registration information
ClinicalTrials.gov; Identifier: NCT00127452. URL: http://www.clinicaltrials.gov/ct2/show/NCT00127452. 相似文献2.
Elizabeth P. Schlaudecker Mark C. Steinhoff Saad B. Omer Monica M. McNeal Eliza Roy Shams E. Arifeen Caitlin N. Dodd Rubhana Raqib Robert F. Breiman K. Zaman 《PloS one》2013,8(8)
Background
Antenatal immunization of mothers with influenza vaccine increases serum antibodies and reduces the rates of influenza illness in mothers and their infants. We report the effect of antenatal immunization on the levels of specific anti-influenza IgA levels in human breast milk. (ClinicalTrials.gov identifier NCT00142389; http://clinicaltrials.gov/ct2/show/NCT00142389).Methods and Findings
The Mother''s Gift study was a prospective, blinded, randomized controlled trial that assigned 340 pregnant Bangladeshi mothers to receive either trivalent inactivated influenza vaccine, or 23-valent pneumococcal polysaccharide vaccine during the third trimester. We evaluated breast milk at birth, 6 weeks, 6 months, and 12 months, and serum at 10 weeks and 12 months. Milk and serum specimens from 57 subjects were assayed for specific IgA antibody to influenza A/New Caledonia (H1N1) using an enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay, and for total IgA using ELISA. Influenza-specific IgA levels in breast milk were significantly higher in influenza vaccinees than in pneumococcal controls for at least 6 months postpartum (p = 0.04). Geometric mean concentrations ranged from 8.0 to 91.1 ELISA units/ml in vaccinees, versus 2.3 to 13.7 ELISA units/mL in controls. Virus neutralization titers in milk were 1.2 to 3 fold greater in vaccinees, and correlated with influenza-specific IgA levels (r = 0.86). Greater exclusivity of breastfeeding in the first 6 months of life significantly decreased the expected number of respiratory illness with fever episodes in infants of influenza-vaccinated mothers (p = 0.0042) but not in infants of pneumococcal-vaccinated mothers (p = 0.4154).Conclusions
The sustained high levels of actively produced anti-influenza IgA in breast milk and the decreased infant episodes of respiratory illness with fever suggest that breastfeeding may provide local mucosal protection for the infant for at least 6 months. Studies are needed to determine the cellular and immunologic mechanisms of breast milk-mediated protection after antepartum immunization.Trial Registration
ClinicalTrials.gov NCT00142389 相似文献3.
Neelke C. van der Weerd Claire H. Den Hoedt Peter J. Blankestijn Michiel L. Bots Marinus A. van den Dorpel Renée Lévesque Albert H. A. Mazairac Menso J. Nubé E. Lars Penne Pieter M. ter Wee Muriel P. C. Grooteman CONTRAST Investigators 《PloS one》2014,9(4)
Resistance to erythropoiesis stimulating agents (ESA) is common in patients undergoing chronic hemodialysis (HD) treatment. ESA responsiveness might be improved by enhanced clearance of uremic toxins of middle molecular weight, as can be obtained by hemodiafiltration (HDF). In this analysis of the randomized controlled CONvective TRAnsport STudy (CONTRAST; NCT00205556), the effect of online HDF on ESA resistance and iron parameters was studied. This was a pre-specified secondary endpoint of the main trial. A 12 months'' analysis of 714 patients randomized to either treatment with online post-dilution HDF or continuation of low-flux HD was performed. Both groups were treated with ultrapure dialysis fluids. ESA resistance, measured every three months, was expressed as the ESA index (weight adjusted weekly ESA dose in daily defined doses [DDD]/hematocrit). The mean ESA index during 12 months was not different between patients treated with HDF or HD (mean difference HDF versus HD over time 0.029 DDD/kg/Hct/week [−0.024 to 0.081]; P = 0.29). Mean transferrin saturation ratio and ferritin levels during the study tended to be lower in patients treated with HDF (−2.52% [−4.72 to −0.31]; P = 0.02 and −49 ng/mL [−103 to 4]; P = 0.06 respectively), although there was a trend for those patients to receive slightly more iron supplementation (7.1 mg/week [−0.4 to 14.5]; P = 0.06).In conclusion, compared to low-flux HD with ultrapure dialysis fluid, treatment with online HDF did not result in a decrease in ESA resistance.
Trial Registration
ClinicalTrials.gov NCT00205556 相似文献4.
Mayu O. Frank Julia Kaufman Suyan Tian Mayte Suárez-Fari?as Salina Parveen Nathalie E. Blachère Michael J. Morris Susan Slovin Howard I. Scher Matthew L. Albert Robert B. Darnell 《PloS one》2010,5(9)
Background
Studies of patients with paraneoplastic neurologic disorders (PND) have revealed that apoptotic tumor serves as a potential potent trigger for the initiation of naturally occurring tumor immunity. The purpose of this study was to assess the feasibility, safety, and immunogenicity of an apoptotic tumor-autologous dendritic cell (DC) vaccine.Methods and Findings
We have modeled PND tumor immunity in a clinical trial in which apoptotic allogeneic prostate tumor cells were used to generate an apoptotic tumor-autologous dendritic cell vaccine. Twenty-four prostate cancer patients were immunized in a Phase I, randomized, single-blind, placebo-controlled study to assess the safety and immunogenicity of this vaccine. Vaccinations were safe and well tolerated. Importantly, we also found that the vaccine was immunogenic, inducing delayed type hypersensitivity (DTH) responses and CD4+ and CD8+ T cell proliferation, with no effect on FoxP3+ regulatory T cells. A statistically significant increase in T cell proliferation responses to prostate tumor cells in vitro (p = 0.002), decrease in prostate specific antigen (PSA) slope (p = 0.016), and a two-fold increase in PSA doubling time (p = 0.003) were identified when we compared data before and after vaccination.Conclusions
An apoptotic cancer cell vaccine modeled on naturally occurring tumor immune responses in PND patients provides a safe and immunogenic tumor vaccine. (ClinicalTrials.gov number NCT00289341).Trial Registration
ClinicalTrials.gov NCT00289341 相似文献5.
Patrizia Maria Carrieri Laurent Michel Caroline Lions Julien Cohen Muriel Vray Marion Mora Fabienne Marcellin Bruno Spire Alain Morel Perrine Roux the Methaville Study Group 《PloS one》2014,9(11)
Objective
Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC.Methods
In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively.Results
In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively).Conclusions
Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence.Trial registration
Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511 相似文献6.
Ammar Al-Chalabi Alexandra Dürr Nicholas W. Wood Michael H. Parkinson Agnes Camuzat Jean-Sébastien Hulot Karen E. Morrison Alan Renton Sigurd D. Sussmuth Bernhard G. Landwehrmeyer Albert Ludolph Yves Agid Alexis Brice P. Nigel Leigh Gilbert Bensimon for the NNIPPS Genetic Study Group 《PloS one》2009,4(9)
Background
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by parkinsonism, cerebellar ataxia and autonomic dysfunction. Pathogenic mechanisms remain obscure but the neuropathological hallmark is the presence of α-synuclein-immunoreactive glial cytoplasmic inclusions. Genetic variants of the α-synuclein gene, SNCA, are thus strong candidates for genetic association with MSA. One follow-up to a genome-wide association of Parkinson''s disease has identified association of a SNP in SNCA with MSA.Methodology/Findings
We evaluated 32 SNPs in the SNCA gene in a European population of 239 cases and 617 controls recruited as part of the Neuroprotection and Natural History in Parkinson Plus Syndromes (NNIPPS) study. We used 161 independently collected samples for replication. Two SNCA SNPs showed association with MSA: rs3822086 (P = 0.0044), and rs3775444 (P = 0.012), although only the first survived correction for multiple testing. In the MSA-C subgroup the association strengthened despite more than halving the number of cases: rs3822086 P = 0.0024, OR 2.153, (95% CI 1.3–3.6); rs3775444 P = 0.0017, OR 4.386 (95% CI 1.6–11.7). A 7-SNP haplotype incorporating three SNPs either side of rs3822086 strengthened the association with MSA-C further (best haplotype, P = 8.7×10−4). The association with rs3822086 was replicated in the independent samples (P = 0.035).Conclusions/Significance
We report a genetic association between MSA and α-synuclein which has replicated in independent samples. The strongest association is with the cerebellar subtype of MSA.Trial Registration
ClinicalTrials.gov NCT00211224. [NCT00211224] 相似文献7.
Kersten Villringer Ulrike Grittner Lars-Arne Schaafs Christian H. Nolte Heinrich Audebert Jochen B. Fiebach 《PloS one》2014,9(10)
Background
There is an ongoing debate whether stroke patients presenting with minor or moderate symptoms benefit from thrombolysis. Up until now, stroke severity on admission is typically measured with the NIHSS, and subsequently used for treatment decision.Hypothesis
Acute MRI lesion volume assessment can aid in therapy decision for iv-tPA in minor stroke.Methods
We analysed 164 patients with NIHSS 0–7 from a prospective stroke MRI registry, the 1000+ study (clinicaltrials.org NCT00715533). Patients were examined in a 3 T MRI scanner and either received (n = 62) or did not receive thrombolysis (n = 102). DWI (diffusion weighted imaging) and PI (perfusion imaging) at admission were evaluated for diffusion - perfusion mismatch. Our primary outcome parameter was final lesion volume, defined by lesion volume on day 6 FLAIR images.Results
The association between t-PA and FLAIR lesion volume on day 6 was significantly different for patients with smaller DWI volume compared to patients with larger DWI volume (interaction between DWI and t-PA: p = 0.021). Baseline DWI lesion volume was dichotomized at the median (0.7 ml): final lesion volume at day 6 was larger in patients with large baseline DWI volumes without t-PA treatment (median difference 3, IQR −0.4–9.3 ml). Conversely, in patients with larger baseline DWI volumes final lesion volumes were smaller after t-PA treatment (median difference 0, IQR −4.1–5 ml). However, this did not translate into a significant difference in the mRS at day 90 (p = 0.577).Conclusion
Though this study is only hypothesis generating considering the number of cases, we believe that the size of DWI lesion volume may support therapy decision in patients with minor stroke.Trial Registration
Clinicaltrials.org NCT00715533 相似文献8.
David C. Nieman Nicholas D. Gillitt Amy M. Knab R. Andrew Shanely Kirk L. Pappan Fuxia Jin Mary Ann Lila 《PloS one》2013,8(8)
Objectives
Polyphenol supplementation was tested as a countermeasure to inflammation and oxidative stress induced by 3-d intensified training.Methods
Water soluble polyphenols from blueberry and green tea extracts were captured onto a polyphenol soy protein complex (PSPC). Subjects were recruited, and included 38 long-distance runners ages 19–45 years who regularly competed in road races. Runners successfully completing orientation and baseline testing (N = 35) were randomized to 40 g/d PSPC (N = 17) (2,136 mg/d gallic acid equivalents) or placebo (N = 18) for 17 d using double-blinded methods and a parallel group design, with a 3-d running period inserted at day 14 (2.5 h/d, 70% VO2max). Blood samples were collected pre- and post-14 d supplementation, and immediately and 14 h after the third day of running in subjects completing all aspects of the study (N = 16 PSPC, N = 15 placebo), and analyzed using a metabolomics platform with GC-MS and LC-MS.Results
Metabolites characteristic of gut bacteria metabolism of polyphenols were increased with PSPC and 3 d running (e.g., hippurate, 4-hydroxyhippurate, 4-methylcatechol sulfate, 1.8-, 1.9-, 2.5-fold, respectively, P<0.05), an effect which persisted for 14-h post-exercise. Fatty acid oxidation and ketogenesis were induced by exercise in both groups, with more ketones at 14-h post-exercise in PSPC (3-hydroxybutyrate, 1.8-fold, P<0.05). Established biomarkers for inflammation (CRP, cytokines) and oxidative stress (protein carbonyls) did not differ between groups.Conclusions
PSPC supplementation over a 17-d period did not alter established biomarkers for inflammation and oxidative stress but was linked to an enhanced gut-derived phenolic signature and ketogenesis in runners during recovery from 3-d heavy exertion.Trial Registration
ClinicalTrials.gov, U.S. National Institutes of Health, identifier: NCT01775384 相似文献9.
Matthias Braun James Young C?cilia S. Reiner Diane Poster Fabienne Krauer Andreas D. Kistler Paulus Kristanto Xueqi Wang Yang Liu Johannes Loffing Gustav Andreisek Arnold von Eckardstein Oliver Senn Rudolf P. Wüthrich Andreas L. Serra 《PloS one》2012,7(10)
Sirolimus has been approved for clinical use in non proliferative and proliferative disorders. It inhibits the mammalian target of rapamycin (mTOR) signaling pathway which is also known to regulate ovarian morphology and function. Preliminary observational data suggest the potential for ovarian toxicity but this issue has not been studied in randomized controlled trials. We reviewed the self-reported occurrence of menstrual cycle disturbances and the appearance of ovarian cysts post hoc in an open label randomized controlled phase II trial conducted at the University Hospital Zürich between March 2006 and March 2010. Adult females with autosomal dominant polycystic kidney disease, an inherited kidney disease not known to affect ovarian morphology and function, were treated with 1.3 to 1.5 mg sirolimus per day for a median of 19 months (N = 21) or standard care (N = 18). Sirolimus increased the risk of both oligoamenorrhea (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.1 to 29) and ovarian cysts (HR 4.4, CI 1.1 to 26); one patient was cystectomized five months after starting treatment with sirolimus. We also studied mechanisms of sirolimus-associated ovarian toxicity in rats. Sirolimus amplified signaling in rat ovarian follicles through the pro-proliferative phosphatidylinositol 3-kinase pathway. Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors.
Trial Registration
ClinicalTrials.gov NCT00346918 相似文献10.
Lynn T. Matthews Sengeziwe Sibeko Leila E. Mansoor Nonhlanhla Yende-Zuma David R. Bangsberg Quarraisha Abdool Karim 《PloS one》2013,8(3)
Background
Antiretroviral prophylaxis may be a critical strategy to reduce periconception HIV transmission. Maximizing the benefit of periconception pharmacologic HIV risk-reduction requires an understanding of the links between pregnancy and adherence to this prevention strategy.Methods
We assessed study gel adherence among women with pregnancies compared to women without pregnancies enrolled in the CAPRISA 004 phase IIB trial of 1% vaginal tenofovir gel. Pregnancy was assessed with monthly urine tests. Adherence was measured monthly and defined as proportion of sex acts covered by two returned, used applicators based on pre- and post-coital dosing. High adherence was defined as a median adherence score of >80%, that is, more than 80% of sex acts were covered by two applications of study gel. A multivariate generalized estimating equations (GEE) model with a binomial distribution was used to assess covariates associated with high adherence (>80%) over time. Median adherence before and after pregnancy was compared using Wilcoxon signed rank test.Results
Among 868 women, 53 had at least 1 pregnancy (4.06 per 100 woman years, 95% CI: 3.04, 5.31). Women with pregnancies had lower median adherence compared to women without pregnancies (50% [IQR: 45–83] vs. 60% [IQR: 50–100], p = 0.02). Women with pregnancies also had a 48% lower odds of high adherence compared to women without pregnancies when adjusting for confounders (aOR 0.52, 95%CI: 0.41–0.66, p<0.0001). Among women with pregnancies, adherence before and after pregnancy was not different (50% [IQR: 46–83] vs. 55% [IQR: 20–100], p = 0.68).Conclusions
Women with pregnancies were less likely to have high adherence to study gel compared to women without pregnancies. Understanding these differences may inform findings from HIV prevention trials and future implementation of antiretroviral prophylaxis for at-risk women who choose to conceive. The protocol for the parent trial is registered on ClinicalTrials.gov, NCT00441298, http://www.clinicaltrials.gov/ct2/show/NCT00441298. 相似文献11.
Shyam Sundar Krishna Pandey Chandreshwar Prasad Thakur Tara Kant Jha Vidya Nand Ravi Das Neena Verma Chandra Shekhar Lal Deepak Verma Shahnawaz Alam Pradeep Das 《PLoS neglected tropical diseases》2014,8(9)
Background
India is home to 60% of the total global visceral leishmaniasis (VL) population. Use of long-term oral (e.g. miltefosine) and parenteral drugs, considered the mainstay for treatment of VL, is now faced with increased resistance, decreased efficacy, low compliance and safety issues. The authors evaluated the efficacy and safety of an alternate treatment option, i.e. single infusion of preformed amphotericin B (AmB) lipid emulsion (ABLE) in comparison with that of liposomal formulation (LAmB).Methods
In this multicentric, open-label study, 500 patients with VL were randomly assigned in a 3∶1 ratio to receive 15 mg/kg single infusion of either ABLE (N = 376) or LAmB (N = 124). Initial cure (Day 30/45), clinical improvement (Day 30) and long term definitive cure (Day 180) were assessed.Findings
A total of 326 (86.7%) patients in the ABLE group and 122 (98.4%) patients in the LAmB group completed the study. Initial cure was achieved by 95.9% of patients in the ABLE group compared to 100% in the LAmB group (p = 0.028; 95% CI: −0.0663, −0.0150). Clinical improvement was comparable between treatments (ABLE: 98.9% vs. LAmB: 98.4%). Definitive cure was achieved in 85.9% with ABLE compared to 98.4% with LAmB. Infusion-related pyrexia (37.2% vs. 32.3%) and chills (18.4% vs. 18.5%) were comparable between ABLE and LAmB, respectively. Treatment-related serious adverse events were fewer in ABLE (0.3%) compared to LAmB (1.6%). Two deaths occurred in the ABLE group, of which one was probably related to the study drug. Nephrotoxicity and hepatotoxicity was not observed in either group.Conclusions
ABLE 15 mg/kg single infusion had favorable efficacy and was well tolerated. Considering the demographic profile of the population in this region, a single dose treatment offers advantages in terms of compliance, cost and applicability.Trial Registration
www.clinicaltrials.gov NCT00876824 相似文献12.
Marina Chiara Garassino Sheila Piva Nicla La Verde Ilaria Spagnoletti Vittorio Iorno Claudia Carbone Antonio Febbraro Anna Bianchi Annalisa Bramati Anna Moretti Monica Ganzinelli Mirko Marabese Marta Gentili Valter Torri Gabriella Farina 《PloS one》2013,8(4)
Purpose
Neuropathic pain is commonly associated with cancer. Current treatments include combination opioid and adjuvant therapies, but no guidelines are available for dose escalation strategies. This phase II study compared the efficacy and tolerability of two dose escalation strategies for oxycodone and pregabalin combination therapy.Methods
Patients (N = 75) with oncological neuropathic pain, previously untreated with pregabalin, were recruited in 5 Italian institutions between 2007 and 2010. Patients were randomised to two different dose escalation strategies (arm A; N = 38) oxycodone at a fixed dose with increasing pregabalin doses; (arm B; N = 37) pregabalin at a fixed dose with increasing oxycodone doses. Patients were evaluated from daily diaries and follow-ups at 3, 7, 10, and 14 days after beginning treatment with a numerical rating scale (NRS), neuropathic pain scale (SDN), and well-being scale (ESAS). The primary endpoint was a ≥1/3 reduction in pain (NRS); secondary endpoints included the time to analgesia and adverse effects. The study had a 90% probability of detecting the best strategy for a true difference of at least 15%.Results
More patients in arm A (76%) than arm B (64%) achieved ≥1/3 overall pain reduction even after controlling for baseline factors (gender, baseline pain). Group A reported fewer side effects than group B; constipation 52.8% vs. 66.7%; nausea: 27.8% vs. 44.4%; drowsiness: 44.4% vs. 55.6%; confusion: 16.7% vs. 27.8%; itching: 8.3% vs. 19.4%.Conclusions
Both strategies effectively controlled neuropathic pain, but according to the adopted selection design arm A is preferable to arm B for pain control.Trial Registration
ClinicalTrials.gov NCT00637975 相似文献13.
Michael Gejl Susanne Lerche Annette Mengel Niels M?ller Bo Martin Bibby Kamille Smidt Birgitte Brock Hanne S?ndergaard Hans Erik B?tker Albert Gjedde Jens Juul Holst S?ren Baarsgaard Hansen J?rgen Rungby 《PloS one》2014,9(1)
Background and Aims
Glucagon-like peptide-1 (GLP-1) may provide beneficial cardiovascular effects, possibly due to enhanced myocardial energetic efficiency by increasing myocardial glucose uptake (MGU). We assessed the effects of GLP-1 on MGU in healthy subjects during normo- and hypoglycemia.Materials and Methods
We included eighteen healthy men in two randomized, double-blinded, placebo-controlled cross-over studies. MGU was assessed with GLP-1 or saline infusion during pituitary-pancreatic normo- (plasma glucose (PG): 4.5 mM, n = 10) and hypoglycemic clamps (PG: 3.0 mM, n = 8) by positron emission tomography with 18fluoro-deoxy-glucose (18F-FDG) as tracer.Results
In the normoglycemia study mean (± SD) age was 25±3 years, and BMI was 22.6±0.6 kg/m2 and in the hypoglycemia study the mean age was 23±2 years with a mean body mass index of 23±2 kg/m2. GLP-1 did not change MGU during normoglycemia (mean (+/− SD) 0.15+/−0.04 and 0.16+/−0.03 µmol/g/min, P = 0.46) or during hypoglycemia (0.16+/−0.03 and 0.13+/−0.04 µmol/g/min, P = 0.14). However, the effect of GLP-1 on MGU was negatively correlated to baseline MGU both during normo- and hypoglycemia, (P = 0.006, r2 = 0.64 and P = 0.018, r2 = 0.64, respectively) and changes in MGU correlated positively with the level of insulin resistance (HOMA 2IR) during hypoglycemia, P = 0.04, r2 = 0.54. GLP-1 mediated an increase in circulating glucagon levels at PG levels below 3.5 mM and increased glucose infusion rates during the hypoglycemia study. No differences in other circulating hormones or metabolites were found.Conclusions
While GLP-1 does not affect overall MGU, GLP-1 induces changes in MGU dependent on baseline MGU such that GLP-1 increases MGU in subjects with low baseline MGU and decreases MGU in subjects with high baseline MGU. GLP-1 preserves MGU during hypoglycemia in insulin resistant subjects.ClinicalTrials.gov registration numbers: NCT00418288: (hypoglycemia) and NCT00256256: (normoglycemia). 相似文献14.
Halvor Rollag Thor Ueland Anders ?sberg Anders Hartmann Alan G. Jardine Atul Humar Mark D. Pescovitz Angelo A. Bignamini P?l Aukrust 《PloS one》2013,8(4)
Background
While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.Patients and Methods
Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.Results
The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.Conclusion
Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease. 相似文献15.
Joaquin Luna Manuel Plata Mauricio Gonzalez Alfonso Correa Ivete Maldonado Claudia Nossa David Radley Scott Vuocolo Richard M. Haupt Alfred Saah 《PloS one》2013,8(12)
Background
Previous analyses from a randomized trial in women aged 24–45 have shown the quadrivalent HPV vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN) and external genital lesions (EGL) related to HPV 6/11/16/18 through 4 years. In this report we present long term follow-up data on the efficacy, safety and immunogenicity of the quadrivalent HPV vaccine in adult women.Methods
Follow-up data are from a study being conducted in 5 sites in Colombia designed to evaluate the long-term immunogenicity, effectiveness, and safety of the qHPV vaccine in women who were vaccinated at 24 to 45 years of age (in the original vaccine group during the base study [n = 684]) or 29 to 50 years of age (in the original placebo group during the base study [n = 651]). This analysis summarizes data collected as of the year 6 post-vaccination visit relative to day 1 of the base study (median follow-up of 6.26 years) from both the original base study and the Colombian follow-up.Results
There were no cases of HPV 6/11/16/18-related CIN or EGL during the extended follow-up phase in the per-protocol population. Immunogenicity persists against vaccine-related HPV types, and no evidence of HPV type replacement has been observed. No new serious adverse experiences have been reported.Conclusions
Vaccination with qHPV vaccine provides generally safe and effective protection from HPV 6-, 11-, 16-, and 18-related genital warts and cervical dysplasia through 6 years following administration to 24–45 year-old women.Trial Registration
Clinicaltrials.gov NCT00090220 相似文献16.
Rationale & Aim
Pulmonary surfactants are essential components of lung homeostasis. In chronic obstructive pulmonary disease (COPD), surfactant expression decreases in lungs whereas, there is a paradoxical increase in protein expression in plasma. The latter has been associated with poor health outcomes in COPD. The purpose of this study was to determine the relationship of surfactants and other pneumoproteins in bronchoalveolar lavage (BAL) fluid and plasma to airflow limitation and the effects of budesonide/formoterol on this relationship.Methods
We recruited (clinical trials.gov identifier: NCT00569712) 7 smokers without COPD and 30 ex and current smokers with COPD who were free of exacerbations for at least 4 weeks. All subjects were treated with budesonide/formoterol 400/12 µg twice a day for 4 weeks. BAL fluid and plasma samples were obtained at baseline and the end of the 4 weeks. We measured lung-predominant pneumoproteins: pro-Surfactant Protein-B (pro-SFTPB), Surfactant Protein-D (SP-D), Club Cell Secretory Protein-16 (CCSP-16) and Pulmonary and Activation-Regulated Chemokine (PARC/CCL-18) in BAL fluid and plasma.Results
BAL Pro-SFTPB concentrations had the strongest relationship with airflow limitation as measured by FEV1/FVC (Spearman rho = 0.509; p = 0.001) and FEV1% of predicted (Spearman rho = 0.362; p = 0.028). Plasma CCSP-16 concentrations were also significantly related to airflow limitation (Spearman rho = 0.362; p = 0.028 for FEV1% of predicted). The other biomarkers in BAL fluid or plasma were not significantly associated with airflow limitation. In COPD subjects, budesonide/formoterol significantly increased the BAL concentrations of pro-SFTPB by a median of 62.46 ng/ml (p = 0.022) or 48.7% from baseline median value.Conclusion
Increased severity of COPD is associated with reduced Pro-SFTPB levels in BAL fluid. Short-term treatment with budesonide/formoterol increases these levels in BAL fluid. Long term studies will be needed to determine the clinical relevance of this observation. 相似文献17.
Background
Today, a large proportion of early abortions are medical terminations, in accordance to the woman''s choice. Intrauterine contraceptives (IUC) provide highly effective, reversible, long-acting contraception. However, the effects of timing of IUC insertion after medical abortion are not known.Methods
Women undergoing medical abortion with mifepristone and misoprostol up to 63 days gestation and opting for IUC were randomised to early insertion (day 5–9 after mifepristone) or delayed (routine) insertion (at 3–4 weeks after mifepristone). The primary outcome was the rate of IUC expulsion at six months after IUC insertion.Results
A total of 129 women were randomized, and 116 women had a successful IUC insertion. There was no difference in expulsion rate between early (9.7%) vs. delayed (7.4%) IUC insertion (risk difference −9.2–13.4). Furthermore, 1.5% of women randomized to early and 11.5% to delayed insertion did not attend the follow up (proportion difference 10.0%, 95% CI: 1.8–20.6%, p = 0.015), and a higher proportion of women (41%) had had unprotected intercourse prior to returning for insertion in the delayed group compared with the early group (16%) (p = 0.015). Adverse events were rare and did not differ between the groups.Conclusions
Early insertion of IUC after medical abortion was safe and well tolerated with no increased incidence for expulsions or complications. Women were more likely to return for the IUC insertion if scheduled early after the abortion, and less likely to have had an unprotected intercourse prior to the IUC insertion. Early insertion should be offered as a routine for women undergoing first trimester medical abortion.Trial Registration
ClinicalTrials.gov NCT01537562 相似文献18.
Robert S. Wallis Rodney Dawson Sven O. Friedrich Amour Venter Darcy Paige Tong Zhu Annette Silvia Jason Gobey Craig Ellery Yao Zhang Kathleen Eisenach Paul Miller Andreas H. Diacon 《PloS one》2014,9(4)
Rationale
Sutezolid (PNU-100480) is a linezolid analog with superior bactericidal activity against Mycobacterium tuberculosis in the hollow fiber, whole blood and mouse models. Like linezolid, it is unaffected by mutations conferring resistance to standard TB drugs. This study of sutezolid is its first in tuberculosis patients.Methods
Sputum smear positive tuberculosis patients were randomly assigned to sutezolid 600 mg BID (N = 25) or 1200 mg QD (N = 25), or standard 4-drug therapy (N = 9) for the first 14 days of treatment. Effects on mycobacterial burden in sputum (early bactericidal activity or EBA) were monitored as colony counts on agar and time to positivity in automated liquid culture. Bactericidal activity was also measured in ex vivo whole blood cultures (whole blood bactericidal activity or WBA) inoculated with M. tuberculosis H37Rv.Results
All patients completed assigned treatments and began subsequent standard TB treatment according to protocol. The 90% confidence intervals (CI) for bactericidal activity in sputum over the 14 day interval excluded zero for all treatments and both monitoring methods, as did those for cumulative WBA. There were no treatment-related serious adverse events, premature discontinuations, or dose reductions due to laboratory abnormalities. There was no effect on the QT interval. Seven sutezolid-treated patients (14%) had transient, asymptomatic ALT elevations to 173±34 U/L on day 14 that subsequently normalized promptly; none met Hy''s criteria for serious liver injury.Conclusions
The mycobactericidal activity of sutezolid 600 mg BID or 1200 mg QD was readily detected in sputum and blood. Both schedules were generally safe and well tolerated. Further studies of sutezolid in tuberculosis treatment are warranted.Trial Registration
ClinicalTrials.gov NCT01225640 相似文献19.
Hanna Fernemark Christine Jaredsson Bekim Bunjaku Ulf Rosenqvist Fredrik H. Nystrom Hans Guldbrand 《PloS one》2013,8(11)
Background
In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets.Objective
To study postprandial effects of three diets, during a single day, in NIDDM.Methods
A low-fat diet (45–56 energy-% from carbohydrates), and a low-carbohydrate diet (16–24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32–35 energy−% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025–1080 kCal in men and 905–984 kCal in women. The test meals were consumed at a diabetes ward under supervision.Results
Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p<0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35±2.2, of Mediterranean-style diet: 8.12±5.2, p = 0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003).Conclusions
The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective.Trial Registration
ClinicalTrials.gov NCT01522157 NCT01522157 相似文献20.
Ronald H. Gray David Serwadda Aaron A. R. Tobian Michael Z. Chen Frederick Makumbi Tara Suntoke Godfrey Kigozi Fred Nalugoda Boaz Iga Thomas C. Quinn Lawrence H. Moulton Oliver Laeyendecker Steven J. Reynolds Xiangrong Kong Maria J. Wawer 《PLoS medicine》2009,6(11)