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31.
Virus dynamics and immune responses during treatment in patients coinfected with hepatitis C and HIV 总被引:2,自引:0,他引:2
Talal AH Shata MT Markatou M Dorante G Chadburn A Koch R Neumann AU Ribeiro RM Perelson AS 《Journal of acquired immune deficiency syndromes (1999)》2004,35(2):103-113
Mathematical modeling of the biological effect of interferon on virus decay permits the quantification of the efficacy (epsilon) of blocking virion production in different patient populations. The viral dynamic and immunologic responses of hepatitis C virus (HCV) infection to daily interferon therapy were characterized in twelve patients co-infected with human immunodeficiency virus (HIV). Three out of the twelve patients (25%) achieved an early viral response, a two-log reduction in HCV RNA by week 12. The mean epsilon of IFN-alpha in blocking HCV and HIV production were 72% and 74%, respectively. For HCV epsilon was highest (97%) in the one patient who had a sustained viral response, while it was reduced in the other two patients (68% and 77%). Baseline HCV RNA and the number of CD3+CD56+16+ cells were inversely related (r = -0.89, p = 0.03), and baseline HCV-specific immune responses were significantly higher in the three patients with 2-log viral load reductions. These data suggest that: 1) interferon efficacy at blocking virion production is correlated with treatment outcome in HIV/HCV co-infected patients, 2) that immunodeficient patients can respond to standard IFN-alpha, 3) that both innate and adaptive immune responses may be important determinants of HCV RNA decline in response to interferon. 相似文献
32.
Patricia M. Portillo Marianthi Ierapetritou Silvina Tomassone Christine Mc Dade Donald Clancy Petrus P. C. Avontuur Fernando J. Muzzio 《Journal of pharmaceutical innovation》2008,3(4):258-270
In this study, a quality by design approach was applied to the design and scale-up of a batch mixing process. Mixtures of
acetaminophen and lactose were sampled at different mixing times using a groove sampler. Samples were subsequently analyzed
using NIR reflection spectroscopy. The effects of four processing parameters on the empirical mixing rate in a bin blender
were examined. Blender rotation rate (two levels), powder fill level (two levels), powder cohesion (two levels), and blender
size (three levels) represent the four parameters studied. Blender geometry and blender loading method were treated as constant
parameters. Statistical analysis was used to assess the impact each parameter had on the mixing rate. Blender size (p = 0.02), powder cohesion (p = 0.05), and rotation rate (p = 0.07) all significantly affected the mixing rate. The least significant parameter was the vessel fill level (p = 0.18), indicating mixing performance is not strongly affected by fill level, given the range studied. 相似文献
33.
Georgitsi M De Menis E Cannavò S Mäkinen MJ Tuppurainen K Pauletto P Curtò L Weil RJ Paschke R Zielinski G Wasik A Lubinski J Vahteristo P Karhu A Aaltonen LA 《Clinical endocrinology》2008,69(4):621-627
Objective Pituitary adenomas occur rarely in childhood and adolescence. Pituitary adenoma predisposition (PAP) has been recently associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The aim of the study was to examine the proportion of germline AIP mutations in apparently sporadic paediatric pituitary adenomas. Design Genomic DNA was analysed for mutations in the AIP gene, by PCR amplification and direct sequencing. Patients A population‐based cohort consisting of 36 apparently sporadic paediatric pituitary adenoma patients, referred to two medical centres in Italy, was included in the study. Patients were either less than 18 years at diagnosis, or showed clinical evidence of adenoma development before the age of 18 years. Results A heterozygous in‐frame deletion Y248del (c.742_744delTAC) was identified in one GH‐secreting adenoma patient. Loss of heterozygosity (LOH) analysis of tumour DNA revealed the loss of the wild‐type allele. First degree relatives carrying the mutation were clinically unaffected. Conclusions While mutations were absent in non‐GH‐secreting adenoma patients, germline AIP mutations can be found in children and adolescents with GH‐secreting tumours, even in the absence of family history. The present study reports the AIP mutation analysis results on patients of a single ethnic origin. Clearly, further studies are needed to improve our knowledge on the role of AIP in paediatric pituitary adenomas. 相似文献
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Determining important associations among items in a large database is challenging due to multiple simultaneous hypotheses and the ability to select weak associations that are statistically but not clinically significant. The simple application of the chi2 test among all possible pairs of items results in mostly inappropriate associations surpassing the traditional (alpha=.05, chi2=3.94) threshold. One can choose a stricter threshold to find stronger associations, but the choice may be arbitrary. We combined the volume test of Diaconis and Efron with a p-value plot to select a more rigorous and less arbitrary threshold. The volume test adjusts the p-value of the chi2-statistic. A plot of adjusted p-values (1 - p versus N(p)), where N(p) is the number of test statistics with a p-value greater than p, should be linear if there are no true associations. The point where the plot deviates from a line can be used as a threshold. We used linear regression to select the threshold in a reproducible fashion. In one experiment, we found that the method selected a threshold similar to that previously obtained by manually reviewing associations. 相似文献
36.
Francesco Testa Andrea Sodi Sabrina Signorini Valentina Di Iorio Vittoria Murro Raffaella Brunetti-Pierri Enza Maria Valente Marianthi Karali Paolo Melillo Sandro Banfi Francesca Simonelli 《Investigative ophthalmology & visual science》2021,62(9)
PurposeThe purpose of this study was to perform a detailed longitudinal phenotyping and genetic characterization of 32 Italian patients with a nonsyndromic retinal dystrophy and mutations in the CEP290 gene.MethodsWe reviewed the clinical history and examinations of 32 patients with a nonsyndromic retinal dystrophy due to mutations in the CEP290 gene, followed up (mean follow-up: 5.9 years) at 3 Italian centers. The clinical examinations included: best corrected visual acuity (BCVA), optical coherence tomography (OCT), and full-field electroretinogram (ERG).ResultsPatients (mean age = 19.0 ± 3.4 years) had a mean BCVA of 1.73 ± 0.20 logMAR. Longitudinal analysis of BCVA showed a nonsignificant decline. Central retinal thickness (CRT) declined significantly with age at an exponential rate of 1.0%/year (P = 0.001). At disease onset, most patients (19/32; 49.4%) had nystagmus. The absence of nystagmus was significantly associated with better BCVA and more preserved CRT (P < 0.05). ERG showed undetectable responses in most patients (64.0%), whereas reduced scotopic and photopic responses were observed in four patients (16.0%) who had no nystagmus. We identified 35 different variants, among which 12 were novel. Our genotype-phenotype correlation analysis shows a significantly worse BCVA in patients harboring a loss-of-function mutation and the deep-intronic variant c.2991+1655A>G.ConclusionsOur study highlights a mild phenotype of the disease, characterized by absence of nystagmus, good visual acuity, considerably preserved retinal morphology, and recordable ERG, confirming the wide spectrum of CEP290-related retinal dystrophies. Finally, in our cohort, the deep intronic variant c.2991+1655A>G was associated with a more severe phenotype. 相似文献
37.
Georgitsi M Papachatzopoulou A Linardaki E Maroulis V Papadakis MN Patrinos GP 《Hemoglobin》2011,35(1):91-95
We report the first heterozygous case of Hb A(2)-NYU (HBD:c.39T>A) in the Hellenic population. The proband, an adult female from the island of Crete, Greece, was identified during routine family screening. DEAE chromatography of the index case revealed a minor hemoglobin (Hb) fraction preceding the elution of the wild-type Hb A(2). DNA sequencing of the entire HBD gene coding regions indicated that the index case was heterozygous for the rare variant Hb A(2)-NYU. Family studies indicated that this Hb variant was inherited from the mother. This finding underlines the vast genetic heterogeneity of the HBD gene in the Hellenic population. 相似文献
38.
Kokras N Politis AM Zervas IM Pappa D Markatou M Katirtzoglou E Papadimitriou GN 《The journal of ECT》2011,27(3):214-220
Electroconvulsive therapy (ECT) is an effective treatment and, with the proper risk-minimizing strategies, is relatively safe even in depressed patients with cardiovascular diseases. Specifically, patients with cardiac rhythm management devices (CRMDs) require particular attention because no controlled trials exist to support current empirical recommendations. We present a depressed patient with a pacemaker successfully treated with ECT, and we critically review the relevant literature. Pooled results from 63 patients and 821 ECT sessions showed that 90% of ECT sessions have been performed on depressed patients with their pacemakers in sensing mode and rate adaptation, where available, activated as well. Only 4% of sessions were performed with those functions disabled, whereas no data was available for 6% of ECT sessions. Pooled results from case series and reports highlight a discrepancy between current clinical practice and many guidelines. Electroconvulsive therapy is probably safe in depressed patients with asynchronous fixed-rate pacemakers, although there is a risk of ventricular tachycardia and fibrillation. A larger body of case series and reports suggests that there might be no need to convert synchronous demand pacemakers to asynchronous fixed-rate pacing. Regarding patients with implantable cardioverter defibrillators, antitachycardia treatment was deactivated during most ECT sessions. In depressed patients with CRMDs anticholinergics might be best avoided. In all cases, proper ECT procedures, namely, patient and pacemaker electrical isolation, strict grounding and adequate muscle relaxation along with interrogation and monitoring of CRMDs before and after each session should ensure uncomplicated electroconvulsive treatments. 相似文献
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40.
Meric A. Ovacik Banalata Sen Susan Y. Euling Kevin W. Gaido Marianthi G. Ierapetritou Ioannis P. Androulakis 《Toxicology and applied pharmacology》2013
Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significance analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data. 相似文献