Przeprowadzona z wykorzystaniem zależnej od ligacji multipleksowej amplifikacji sond analiza genów KAL1, GNRH1, GNRHR, PROK2 i PROKR2 u pacjentów płci męskiej z idiopatycznym hipogonadyzmem hipogonadotropowym

Introduction: The purpose of this study was to determine the prevalence of KAL1, GNRH1, GNRHR, PROK2, and PROKR2 copy numbervariations in patients with idiopathic hypogonadotropic hypogonadism (IHH).Material and methods: 86 hypogonadal males (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism [nIHH] andten with Kallmann syndrome [KS]) and 95 healthy control individuals were studied for the presence of aforementioned genomic rearrangements,using multiplex ligation dependent probe amplification (MLPA).Results: We detected that of the 86 patients, three with KS had a deletion of the KAL1 gene in exon 9, one of whom also carried a duplicationin exon 11; and three with nIHH had a duplication of the PROK2 gene in exon 3; a deletion of the GNRHR gene in exon 1; anda duplication of the same gene in exon 2, respectively. No abnormalities were found in the patient group for the PROKR2 and GNRH1genes. In addition, no genomic rearrangements were identified in the healthy control individuals for the described genes.Conclusions: Defining the genetic basis of disease is essential to improve our understanding of this complex disorder, and could be usefulfor genetic counselling and for directing therapy. In addition, discovering the association between genetic mutations and disease isimportant for our better understanding of normal reproductive functions.Wstęp: Celem badania było ustalenie rozpowszechnienia zmienności liczby kopii genów KAL1, GNRH1, GNRHR, PROK2 i PROKR2u pacjentów z idiopatycznym hipogonadyzmem hipogonadotropowym (IHH, idiopathic hypogonadotropic hypogonadism).Materiał i metody: Obecność wymienionych wyżej rearanżacji genomowych zbadano metodą zależnej od ligacji multipleksowej amplifikacjisond (MLPA, multiplex ligation dependent probe amplification) u 86 mężczyzn z hipogonadyzmem — w tym u 76 z rozpoznaniemIHH przebiegającego bez zaburzeń węchu (nIHH, normosmic idiopathic hypogonadotropic hypogonadism) i u 10 z rozpoznaniem zespołuKallmanna (KS, Kallmann syndrome) — oraz u 95 zdrowych osobników kontrolnych.Wyniki: U 3 pacjentów z KS stwierdzono delecję w obrębie genu KAL1 w egzonie 9, przy czym u jednego z nich występowała też duplikacjaw egzonie 11. Z kolei łącznie u 3 pacjentów z nIHH stwierdzono: duplikację w obrębie genu PROK2 w egzonie 3 u jednego pacjenta,delecję w obrębie genu GNRHR w egzonie 1 u drugiego pacjenta oraz duplikację obrębie tego samego genu w egzonie 2. Jeśli zaś chodzi ogeny PROKR2 i GNRH1, to w grupie pacjentów nie stwierdzono żadnych nieprawidłowości w tym zakresie. Nie stwierdzono też żadnychrearanżacji genomowych w zakresie wymienionych genów u zdrowych osobników kontrolnych.Wnioski: Określanie podłoża genetycznego ma ogromne znaczenie dla pogłębiania wiedzy na temat tej złożonej choroby i możebyć przydatne w poradnictwie genetycznym i ustalaniu leczenia. Ponadto odkrywanie powiązań pomiędzy mutacjami genetycznymia omawianą chorobą ma duże znaczenie dla pogłębiania wiedzy na temat prawidłowego funkcjonowania układu rozrodczego

Richter's transformation presenting with superior vena cava syndrome

In the present study, we report a 65-year old man who had been diagnosed earlier as having chronic lymphocytic leukemia and treated for 2 years with fludarabine. He presented to our hospital 2 years later with clinical features of superior vena cava syndrome. The underlying cause was diffuse large B cell lymphoma obstructing the superior vena cava

IL-33 AND ST2 LEVELS IN CHRONIC KIDNEY DISEASE: ASSOCIATIONS WITH INFLAMMATION, VASCULAR ABNORMALITIES, CARDIOVASCULAR EVENTS AND SURVIVAL

WOS: 000469797100395

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival

WOS: 000403280900026PubMed ID: 28614418Objective Increased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE). Methods This was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1-5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival. Results IL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000). Conclusion This is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients

WOS: 000393616400011PubMed ID: 27378685Introduction: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. Methods: Forty-five hemodialysis patients were included in the study (age: 61.93 +/- 613.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. Findings: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. Discussion: In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.Ahi Evran University Scientific Research Projects Unit [PYO.TIP.4001.15.001]This study was supported by the Ahi Evran University Scientific Research Projects Unit (Project Number PYO.TIP.4001.15.001)

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival.

Increased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE).This was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1-5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival.IL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000).This is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients

Univariate and multivariate COX analysis predicting for cardiovascular outcomes (a composite of 68 fatal and non-fatal CV events).

<p>Univariate and multivariate COX analysis predicting for cardiovascular outcomes (a composite of 68 fatal and non-fatal CV events).</p

Univariate associates of IL 33 and ST2 in non-dialysis CKD patients.

<p>Univariate associates of IL 33 and ST2 in non-dialysis CKD patients.</p