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1.
2.

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   
3.
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   
4.
The effect of a newly developed patellar realignment brace was evaluated in 21 patellofemoral joints (19 patients) with patellar subluxation (13 joints with lateral subluxation and eight with medial subluxation) by using active-movement, loaded kinematic magnetic resonance (MR) imaging. Sixteen patellofemoral joints (76%) demonstrated a qualitative correction of or improvement in patellar subluxation (ie, centralization of the patella or a decrease in the displacement of the patella) after application of the brace. Four of the five “failures” occurred in patellofemoral joints that had patella alta and/or dysplastic bone anatomy. These results indicate that the patellar realignment brace was able to counteract patellar subluxation in the majority of patellofemoral joints studied, as shown by active-movement, loaded kinematic MR imaging. This brace appears to be useful for conservative treatment of patients with patellofemoral joint pain secondary to patellar malalignment and maltracking.  相似文献   
5.
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   
6.
In order to provide a precise lymph node mapping during lung cancer surgery a sterilizable plastic tray moulded in the shape of the mediastinum and lungs is presented by the author. The device makes lymph node mapping simpler, safer, quicker and methodically more structured. A positive impact is expected as a result of usage of the device from making pathologist's work easier and facilitating the flux of information on the surgeon-pathologist-oncologist-pneumonologist chain to be more disinformation-free.  相似文献   
7.
Current surgical treatment of thoracic empyema in adults.   总被引:1,自引:0,他引:1  
A review of the recent literature on treatment modalities of adult thoracic empyema was conducted in order to expose the controversies and verify where consensus exists. Critical reading filtered through clinical experience was the method followed. The roles of surgical drainage, lavage techniques, debridement via VATS, decortication, thoracoplasty and open window thoracostomy were considered using the Oxford Center of Evidence Based Medicine criteria. The roles of the different therapeutical modalities were interpreted in the light of the triphasic nature of empyema thoracis. The randomised controlled trials came up with conflicting results. With two exceptions all of the papers reviewed provide level (2b) or below evidences. The lack of a single ideal treatment modality or policy reflects the complexity of the diagnosis and staging of this heterogeneous disease. Basic elements of intervention--drainage, different evacuation techniques, decortication, thoracoplasty and open window thoracostomy--are well-established technical modalities; however, neither a universally acceptable primary modality nor the gold standard of their sequence is available. Drainage remains to be the initial treatment modality in Phase I disease. Debridement via VATS is a safe, reliable and efficient method in the fibrinopurulent phase. Organised pleural callus requires formal decortication. Open window thoracostomy is a simple and safe procedure for high-risk patients and results in quick detoxication. Thoracoplasty kept its final role in pleural space management. Acute postoperative bronchial stump insufficiency requires immediate surgery. Evacuation of toxic material is mandatory. No single-stage procedure offers a solution. An optimised agressivity treatment modality should be tailored to the condition of the patient and to the potential of the persisting cavity. Decision-making involves a triad consisting of the aetiology of empyema (i.e. primary vs secondary), general condition of the patient and stage of disease, while considering the triphasic nature of development of thoracic empyema. The current attitudes show that the present concepts are based mainly on expert opinion. Flexibility and patience on behalf of the surgeon and nursing staff, the patient and the hospital management, as well as a good understanding of the complexity of this condition are the cornerstones of the treatment. No exclusive sequence of procedures leading to a uniformly predictable successful outcome is available. Individualised approaches can be recommended based on institutional practice and local protocols. Thoracic empyema in general seems to remain resilient to fit completely into the categories of evidence-based medical approach.  相似文献   
8.
Cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5HIAA), homovanillic acid, and tryptophan were measured in 33 depressed, 36 alcoholic, and 32 neurological control female patients selected by strict operational criteria and investigated under controlled circumstances. Plasma total tryptophan was also measured in blood samples taken simultaneously with lumbar punctures. A multivariate regression analysis was done to discover the effect of age, height, and body weight on these four biochemical measures. Only CSF 5HIAA was significantly dependent on the nonspecific patient variables: height, but neither age nor weight, accounted for more than 10% of the variance of 5HIAA. The same analysis was carried out in all three separate patient groups: the relationship between height and CSF 5HIAA was present throughout, and only 2 of 12 correlations proved to be non-homogeneous. To demonstrate the significantly of these clinical parameters a multivariate analysis of covariance was done to eliminate their effect on the four biochemical variables. As a result significant differences emerged in CSF 5HIAA and total plasma tryptophan for some of the patient groups which were not demonstrable without this correction.  相似文献   
9.
Psychological distress was observer-rated with the Brief Psychiatric Rating Scale (BPRS) and self-rated with the Symptom Questionnaire (SQ) every other week for a 6-month period in 9 apparently remitted bipolar patients attending a lithium clinic. Substantial clinical fluctuations in psychopathology were observed with both rating methods. Compared to normal control subjects, patients suffering from bipolar disorder displayed significantly higher BPRS and SQ anxiety, somatization and total distress scores.  相似文献   
10.
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   
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