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1.

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.
The association between contralateral stimulation and evoked otoacoustic emissions (EOAEs) allows study of sound-evoked olivocochlear feedback and then of the medial olivocochlear system. A method allowing quantification of sound-evoked olivocochlear feedback is proposed. The feedback is present in almost all normal-hearing subjects, but with great interindividual variability. In sensorineural hearing loss, the feedback is present in 20 out of 21 subjects. One paradoxical clinical case is described with a unilateral increase of EOAE intensity during contralateral stimulation.  相似文献   
3.
This case report describes a successful pregnancy and deliveryin a woman presenting with ovarian autoimmunity who had previouslybeen involved in two unsuccessful in-vitro fertilization (IVF)attempts. Ten days before a third attempt, she began a regimenof 25 mg per day of prednisolone which was continued throughoutthe whole IVF protocol. Ovulation was induced by human menopausalgonadotrophin. After administration of 5000 IU of human chorionicgonadotrophin, 18 oocytes were collected. At 48 h after inseminationwith the patient's husband's spermatozoa, four 4-cell pre-embryoswere transferred. A singleton pregnancy developed and led tothe birth of a girl who is doing well 10 months later.  相似文献   
4.
Immunologic typing has demonstrated considerable heterogeneity among the acute leukemias. The most significant recent advance has been development of monoclonal antibody techniques. Some markers identified using these techniques seem to be specific for a given stage of maturation of one lymphoid or myeloid cell line. Most acute lymphoblastic leukemias (ALLs) are malignant proliferations whose differentiation appears to have become 'stuck' at one stage of maturation. Results of immunologic typing correlate well with the other clinical and biological data. For prognostic purposes, several patterns can be identified. Among B line ALLs, four varieties have been differentiated, i.e., CD10 negative ALLs, common ALLs, pre-B ALLs, and B ALLs. T ALLs include a broad spectrum of heterogeneous proliferations whose immunologic classification is made difficult by the large number of phenotypes encountered. Among acute myeloblastic leukemias (AMLs), some highly undifferentiated forms have been recognized, by means of immunologic typing, as originating in one of the myeloid cell lines. However, the nosologic and prognostic significance of these studies is less obvious than in ALLs.  相似文献   
5.
Ring-opening metathesis copolymerization of 5-norbornen-2-yl
  • 1 System. name: bicyclo[2.2.1]hept-5-en-2-yl.
  • acetate (NBEAc; 80% endo) with cyclooctene (COE) and norbornene
  • 2 System. name: bicyclo[2.2.1]hept-2-ene.
  • (NBE) was studied using WCl6/(CH3)4Sn as catalytic system. The copolymerization parameters (r1 = r2 = 1 for the NBEAc/NBE system and r1 = 1/r2 = 132 for the NBEAc/COE system) show that the reactivity of the monomers is not affected by the presence of an ester substituent but that it depends on the structure of the hydrocarbon cycle. Thus the well known inhibition effect of the ester group may be concluded not to lie in the propagation step of the catalytic cycle.  相似文献   
    6.
    Patients with renal failure represent a population at risk for hepatitis B, since only 50 to 60% of them develop protective humoral responses after vaccination. As this could be due to an altered regulation of cellular immune responses, the objectives of the present study were to evaluate the proliferative abilities of lymphocytes from patients with chronic renal failure after stimulation in vitro with a mitogen (pokeweed mitogen [PWM]) or HBsAg. In order to differentiate between the immunodeficiency associated with renal failure and that due to immunosuppression posttransplantation, the same subjects were tested before and 4 months after kidney transplantation. The lymphoproliferation assay used was performed by flow cytometry, which is based on sequential analysis of the cell cycle and which allows analysis of cytokine production. Serologically, the group of 36 patients tested comprised 22% nonresponders, 30% poor responders, and 48% responders. Lymphocyte growth was observed for all patients after stimulation with PWM, indicating that these cells had the capacity to proliferate in vitro. The level of lymphoproliferation in response to PWM was significantly reduced after transplantation, yet both before and after transplantation, all serologic nonresponders developed cellular responses to at least two vaccines. No correlation between humoral and cellular responses was shown. Proliferating cells were lymphocytes, which mostly secreted interleukin 4 (IL-4) and IL-10 for the three serologic groups. This study suggests that even when repeated vaccination fails to induce significant antibody levels in patients with renal failure, specific HBs cellular responses develop, and these may prove to be efficient in protecting these patients against hepatitis B.  相似文献   
    7.
    Anhydrotetracycline oxygenase was purified both by affinity chromatography and by hydrophobic interaction chromatography. Molecular weight of anhydrotetracycline oxygenase was determined to be 115,000 by Sephadex G-200 gel filtration. Using preparative isoelectric focusing the isoelectric point of the enzyme was estimated to be 5.3. The enzyme showed a sensitivity to thiol-specific inhibitors. During the hydrophobic interaction purification step, the activity dropped considerably. Reactivation occurred when a heat treated crude extract was added to the reaction mixture.  相似文献   
    8.
    Neurosurgical Review - To assess automated volumetric analysis as a potential presurgical diagnostic tool or as a method to potentially shed light on normal pressure hydrocephalus (NPH)...  相似文献   
    9.
    10.
    Multiphenotypic acute leukemias (MAL), defined by the coexpression on most blast cells of antigens classically attributed to different lineages, remain a rare event. We isolated a series of 26 such cases from a cohort of 1565 leukemic patients whose cells were immunophenotyped at diagnosis. Markers of B and myeloid lineage (BM) were associated in 16 cases (62%), 3 coexpressed B and T markers (BT), and T-cell and myeloid antigens (TM) were found in 7 (27%). A tumoral syndrome was observed in 69% of the patients, without significant differences between the immunophenotypic subgroups. Median event free survivals in the three immunophenotypic subgroups as defined were respectively 24 months for BM-MAL, 4 months for TM-MAL and 7 months for BT-MAL respectively. The poorer prognosis of TM-MAL was significantly different from that of BM-MAL (p < 0.001). This concurred with the poorer prognosis associated with CD7 expression or absence or CD10, both characteristic features of TM-MAL.  相似文献   
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