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1.
Giorgio Gandaglia Guillaume Ploussard Massimo Valerio Agostino Mattei Cristian Fiori Nicola Fossati Armando Stabile Jean-Baptiste Beauval Bernard Malavaud Mathieu Roumiguié Daniele Robesti Paolo Dell’Oglio Marco Moschini Stefania Zamboni Arnas Rakauskas Francesco De Cobelli Francesco Porpiglia Francesco Montorsi Alberto Briganti 《European urology》2019,75(3):506-514
Background
Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.Objective
To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies.Design, setting, and participants
A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified.Outcome measurements and statistical analyses
Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated.Results and limitations
Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC).Conclusions
Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting.Patient summary
We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI. 相似文献2.
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Paramecium calcium channels are blocked by a family of calmodulin antagonists. 总被引:3,自引:0,他引:3 下载免费PDF全文
B E Ehrlich A R Jacobson R Hinrichsen L M Sayre M A Forte 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(15):5718-5722
Although the voltage-sensitive Ca channel present in Paramecium has been subjected to detailed physiological and genetic analysis, no organic ligands have been described that block this channel with high affinity and that ultimately can be used to identify channel components. Based on a previous observation that the naphthalene sulfonamide calmodulin antagonist W-7 can block Paramecium Ca channels at high concentration, we have synthesized analogs of W-7 that block these channels at concentrations of less than 1 microM. The effectiveness of these compounds was tested both by a sensitive behavioral assay and on Ca channels that had been incorporated into planar lipid bilayers. Despite the fact that these compounds are effective Paramecium calmodulin antagonists, two independent lines of evidence suggest that W-7 and its analogs block the Ca channel by a mechanism that is independent of their action on calmodulin. In addition, the sensitivity to W-7 or dihydropyridines of Ca channels present in a number of eukaryotic phyla has been used to identify similarities in Ca channels from widely diverse organisms. It appears that the pharmacological specificity provides a means to group Ca channels. 相似文献
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Luiz H Castro Luiz K Ferreira Leandro R Teles Carmen L Jorge Paula R Arantes Carla R Ono Carla C Adda Rosa F Valerio 《Seizure》2007,16(1):50-58
PURPOSE: Hypothalamic hamartoma (HH) related epilepsy presents with gelastic seizures (GS), other seizure types and cognitive deterioration. Although seizure origin in GS has been well established, non-GS are poorly characterized. Their relationship with the HH and cognitive deterioration remains poorly understood. We analyzed seizure type, spread pattern in non-GS and their relationship with the epileptic syndrome in HH. METHODS: We documented all current seizure types in six adult patients with HH-epilepsy with video-EEG monitoring, characterized clinical-electrographic features of gelastic and non-gelastic seizures and correlated these findings with cognitive profile, as well as MRI and ictal SPECT data. RESULTS: Only four seizure types were seen: GS, complex partial (CPS), tonic seizures (TS) and secondarily generalized tonic-clonic seizures (sGTC). An individual patient presented either CPS or TS, but not both. GS progressed to CPS or TS, but not both. Ictal patterns in GS/TS and in GS/CPS overlapped, suggesting ictal spread from the HH to other cortical regions. Ictal SPECT patterns also showed GS/TS overlap. Patients with GS-CPS presented a more benign profile with preserved cognition and clinical-EEG features of temporal lobe epilepsy. Patients with GS-TS had clinical-EEG features of symptomatic generalized epilepsy, including mental deterioration. CONCLUSIONS: Video-EEG and ictal SPECT findings suggest that all seizures in HH-related epilepsy originate in the HH, with two clinical epilepsy syndromes: one resembling temporal lobe epilepsy and a more catastrophic syndrome, with features of a symptomatic generalized epilepsy. The epilepsy syndrome may be determined by HH size or by seizure spread pattern. 相似文献
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G Clementi M Grassi C Valerio A Prato C E Fiore F Drago 《Pharmacology, biochemistry, and behavior》1992,42(3):545-548
The effects of central administration of calcitonin gene-related peptide (CGRP, 1 or 100 ng/rat) on behavioral and biochemical parameters related to the extrapyramidal motor system were investigated in male rats. The peptide-induced catalepsy occurred only at the dose of 100 ng/rat and hypomotility at both doses used. Calcitonin gene-related peptide increased haloperidol-induced catalepsy and decreased apomorphine-induced hypermotility at the doses of 1 and 100 ng/rat. Although these behaviors are related to dopamine, no significant change of striatal DA or DOPAC concentration were observed after central administration of the peptide. Other neurotransmitters may be directly or indirectly involved in these behavioral effects of CGRP. 相似文献
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Effect of total parenteral nutrition with intravenous fat on lipids and high density lipoprotein heterogeneity in neonates 总被引:1,自引:0,他引:1
T M Forte O Genzel-Boroviczeny M A Austin L C Kao C Scott J J Albers A E D'Harlingue 《JPEN. Journal of parenteral and enteral nutrition》1989,13(5):490-500
Plasma lipid concentrations and high density lipoprotein (HDL) subclass distributions were evaluated in 22 newborn infants nourished with intravenous (iv)-fat. The majority of infants were premature with respiratory distress syndrome. Based on baseline (prior to iv-fat) HDL subclass profiles determined by gradient gel electrophoresis (GGE), infants fell into two classes, one with two or more pronounced peaks within the normal HDL spectrum (group I, 17 subjects) and the other with highly unusual HDL distribution (group II, five subjects). Total plasma cholesterol increased in both groups during low and high fat intravenous feeding. HDL-cholesterol, however, did not change with iv-fat where mean values for groups I and II at baseline, iv-low fat and -high fat were: group I, 31.2 +/- 7.1, 30.0 +/- 8.8, and 36.6 +/- 16.7 mg/dl, respectively; and group II, 20.0 +/- 7.8, 20.2 +/- 7.4, and 19.8 +/- 8.8 mg/dl, respectively. Unlike HDL-cholesterol levels that remained constant with iv-fat, apolipoprotein (apo) AI concentrations increased significantly: group I, 73.0 +/- 11.0, 88.3 +/- 15.9, and 93.1 +/- 21.9 mg/dl, respectively; and group II, 31.8 +/- 10.5, 41.0 +/- 12.8, and 59.3 +/- 18.5 mg/dl, respectively. In group I infants, iv-fat is associated with an increase in larger-sized particles, particularly in the (HDL2b)gge range; in group II there is an increase in (HDL3b)gge and (HDL3c)gge components and a disappearance of particles that fall outside of the size range of normal HDL. In both groups, enteral feeding is associated with a further normalization of HDL subclass distribution. The aberrant GGE profiles and very low apoAI levels of group II infants at baseline were associated with unusual HDL morphology determined by electron microscopy where discoidal structures were prominent. With iv-fat, discoidal particles decline in number while normal spherical structures increase. Prevalence of discoidal HDL at baseline was associated with low concentrations of lecithin:cholesterol acyltransferase (LCAT) (1.12 +/- 0.5 micrograms/ml); with iv-fat this enzyme rose to 1.61 +/- 0.18 micrograms/ml. Increased LCAT is associated with the normalization of HDL morphology. It is likely that iv-fat improves the nutritional status of premature infants, thereby stimulating increased liver synthesis of important proteins, including apoAI and LCAT, associated with HDL metabolism. 相似文献
10.
Few reports have described conditions under which nicotine self-administration occurs in rats. In this study, rats which initially lever pressed for cocaine infusion (0.05 mg/kg) during 1 h experimental sessions continued to obtain similar infusion numbers when nicotine (0.03 mg/kg) was available. When saline was substituted for nicotine, infusions decreased from 11.8±4.5/h to 5.4±1.1/h but returned to pre-saline levels when it was reintroduced (12.0±5.5/h). These results indicate that nicotine can serve as a positive reinforcer for rats under the historical and schedule conditions described. 相似文献