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1.
Béla Nagy Zsolt Bene Zsolt Fejes Sonya L. Heltshe David Reid Nicola J. Ronan Yvonne McCarthy Daniel Smith Attila Nagy Elizabeth Joseloff György Balla János Kappelmayer Milan Macek Scott C. Bell Barry J. Plant Margarida D. Amaral István Balogh 《Journal of cystic fibrosis》2019,18(2):271-277
Background
We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.Methods
In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).Results
After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).Conclusions
This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy. 相似文献2.
Maher Saqqur MD Michael D. Hill MD MSc FRCPC Andrei V. Alexandrov MD Jayanta Roy MD Marcia Schebel BSc Andrea Krol BSc Zsolt Garami MD Ashfaq Shuaib MD FRCPC Andrew M. Demchuk MD FRCPC 《Journal of neuroimaging》2006,16(4):323-328
BACKGROUND: Stringent transcranial Doppler (TCD) criteria for diagnosing occlusion are needed for more reliable TCD performance at bedside in the acute stroke setting. SUBJECTS AND METHODS: At three academic stroke centers, we performed TCD examination for patients with symptoms of cerebral ischemia who underwent digital subtraction angiography (DSA). We used a standard insonation protocol with power M-mode Doppler (PMD) TCD (TCD 100 M, Spencer Technologies Inc., Seattle, WA). We collected mean flow velocity (MFV), pulsatility indices (PI), and power M-mode resistance signature (absent, high, or low) in symptomatic middle (MCA), anterior (ACA), posterior (PCA), and in affected (a), ipsilateral (i), and contralateral (c-lat) cerebral arteries. Ratios of aMCA/c-lat MCA, aMCA/iACA, and aMCA/iPCA MFV were subsequently calculated. PMD-TCD flow findings were evaluated with a receiver-operating characteristic (ROC) analysis for angiographically proven MCA occlusion. RESULTS: We studied 120 patients with acute cerebral ischemia with PMD-TCD examinations prior to or immediately after DSA. Lower aMCA velocities pointed to higher probability of occlusion (P= .055). The aMCA/iPCA MFV ratio was superior to the aMCA/iACA ratio and strongly predictive of occlusion at a threshold ratio of 0.5 (RR 2.31 CI(95) 2.13-2.51). High resistance or absent M-mode flow signatures in the proximal MCA were present in 87% of M1 and M2 MCA occlusions (probability 87%). In the presence of a low-resistance PMD signature, obtaining the aMCA/iPCA MFV ratio <0.5 increases probability of occlusion to 87%. Normal MFV ratios and low-resistance M-mode signatures are highly predictive of a negative angiogram for MCA occlusion. CONCLUSION: In acute cerebral ischemia, reliable criteria for proximal MCA occlusion have been developed based on combination of MFV ratios and M-mode flow resistance signatures. Validation of these criteria will require multicenter studies. 相似文献
3.
C De Micheli M De Amici F Platini D Della Bella 《Il Farmaco; edizione scientifica》1986,41(12):913-925
A series of pyrroles bearing an ethanol- or an iso-propanolamine side-chain in the beta-position was prepared and their adrenergic activity evaluated. The absence of any appreciable activity suggests that the pyrrole ring is not suitable for replacing the phenol nucleus in derivatives possessing an adrenergic activity. Noteworthy is the amphetamine-like activity observed in amino-ketone (XXIII). 相似文献
4.
F. Deulofeu J. M. Nava F. Bella C. Martí M. A. Morera B. Font D. Fontanals J. Lite J. Garau A. Calderón M. T. Coll S. Uriz V. Pineda 《European journal of clinical microbiology & infectious diseases》1994,13(8):633-638
The incidence and characteristics of invasiveHaemophilus influenzae disease were studied in 43 adult patients admitted to the acute care hospitals in El Vallés County (Barcelona, Spain) between January 1987 and June 1992. The annual incidence ofHaemophilus influenzae disease was 1.2 per 100,000 inhabitants. Pneumonia occurred in 24 patients, meningitis in five, intraabdominal infections in three, obstetric infections in two, epiglottitis in two and cellulitis in one. In six patients the source of infection was unknown. Ten (23 %) of the infections were hospital acquired. Underlying conditions were diagnosed in 30 (70 %) patients. NontypeableHaemophilus influenzae strains predominated in all adult age groups. Sixty-one percent of type b and 34 % of nontypeable strains were ampicillin resistant (p=0.08). Multiple antibiotic resistance was also high among type b (53 %) and nontypeable (18 %) strains. The mortality rate was significantly higher in patients with pneumonia, bactaeremia from an unidentified focus or shock at presentation. 相似文献
5.
6.
Valerie J. Gillet Glenn Myatt Zsolt Zsoldos A. Peter Johnson 《Perspectives in Drug Discovery and Design》1995,3(1):34-50
Summary Several components of a system for structure generation are now well developed. HIPPO is a program that characterises a receptor binding site for potential target sites within the cavity that can be used in de novo design. The target sites include simple and complex hydrogen bonds, covalent bonds and bonds to metal ions. The SPROUT program for structure generation consists of two main components: the first is skeleton generation, followed by atom substitution to convert the solution skeletons to molecules. A new method of skeleton generation is presented here, where part skeletons are grown outwards from each target site. The part skeletons are then connected together to form solution skeletons. Finally the CAESA program is described, that ranks the output from SPROUT according to ease of synthesis. 相似文献
7.
8.
9.
Baldauf ZB 《Neuroscience letters》2005,383(1-2):109-114
The distribution pattern of SMI-32-immunoreactivity (SMI-32-ir) of neuronal elements was examined in the visual cortical areas of marmoset monkey. Layer IV of the primary visual cortex (V1) and layers III and V of the extrastriate areas showed the most abundant SMI-32-ir. The different areal and laminar distribution of SMI-32-ir allowed the distinction between various extrastriate areas and determined their exact anatomical boundaries in the New World monkey, Callithrix penicillata. It is shown here that the parcellating nature of SMI-32 described earlier in the visual cortical areas of other mammals - including Old World monkeys - is also present in the marmoset. Furthermore, a comparison became possible between the chemoanatomical organization of New World and Old World primates' visual cortical areas. 相似文献
10.
Effects of chemical mediators of anaphylaxis on ciliary function 总被引:2,自引:0,他引:2
Adam Wanner M.D. David Maurer Ph.D. William M. Abraham Ph.D. Zsolt Szepfalusi Marek Sielczak M.D. 《The Journal of allergy and clinical immunology》1983,72(6):663-667
We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function. 相似文献