BackgroundWe aimed to assess the current state of PKU screening and management in the region of southeastern Europe.MethodsA survey was performed involving all identified professionals responsible for the PKU management in the 11 countries from South-Eastern region of Europe (Albania, Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Macedonia, Moldova, Montenegro, Romania, Serbia, Slovenia). The questionnaire was designed to assess the characteristics regarding PKU management in three main areas: nation-wide characteristics, PKU screening, and characteristics of the PKU management in the responding centre. It consisted of 56 questions. The distribution and collection of the questionnaires (via e-mail) was taking place from December 2013 to March 2014.ResultsResponses from participants from 11 countries were included; the countries cumulative population is approx. 52.5 mio. PKU screening was not yet introduced in 4 of 11 countries. Reported PKU incidences ranged from 1/7325 to 1/39338 (and were not known for 5 countries). National PKU guidelines existed in 5 of 11 countries and 7 of 11 countries had PKU registry (registries included 40 to 194 patients). The number of PKU centers in each country varied from 1 to 6. Routine genetic diagnostics was reported in 4 of 11 countries. Most commonly used laboratory method to assess phenylalanine levels was fluorometric. Tetrahydrobiopterine was used in only 2 of 11 countries. Most frequently, pediatricians were caring for the patients. Dietitian was a member of PKU team in only 4 of 11 countries, while regular psychological assessments were performed in 6 of 11 countries. Patient’s PKU society existed in 7 of 11 countries.ConclusionsThe region of southeastern Europe was facing certain important challenges of PKU screening and management. Neonatal PKU screening should be introduced throughout the region. Furthermore, PKU management was falling behind internationally established standards-of-care in many aspects.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0283-0) contains supplementary material, which is available to authorized users.
Our results showed that these patients with similar clinical findings had significantly different mediator profiles in their nasal secretions, implying clear differences in pathogenesis of their NP.
Aims. Cytokine levels in nasal secretions reflect the inflammatory status of the nasal and paranasal sinus mucosa and the development of mucosal disease. The results of previous investigations suggest that macrolide antibiotics can be effective in treatment of chronic rhinosinusitis and nasal polyposis. The aim of this prospective study was to compare the immunomodulatory and clinical effects of long-term low-dose macrolide treatment of nonatopic and atopic patients with nasal polyposis.Methods. Forty (n = 40) patients with nasal polyposis, 22 allergic and 18 nonallergic were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory Th1 cytokines TNF-α and IL-1β, Th2 cytokines IL-4, IL-5 and IL-6, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using flow cytometric method. We also scored each of the 40 patients before and after therapy according to nasal symptom score and endoscopic score.Results. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions in nonallergic patients. In subjects with nasal polyposis and allergy, we found decreased levels of IL-8 (p<0.01), IL-6 (p<0.05) and IL-1β (p<0.01). Macrolide therapy decreased the size of polyps in 45.45% of nonatopic and in 50% of atopic patients. After macrolide treatment, we found 67.83% patients in nonallergic group and 55.55% patients in allergic group with improved nasal symptoms.Conclusions. Long-term low-dose treatment with CAM was effective in the management of nasal polyposis. Our results showed that macrolide treatment of nasal polyposis have different immunomodulatory and similar clinical effects in allergic and nonallergic patients.
The aim of this study was to compare the cytokine levels in nasal fluid in subjects with nasal polyposis (NP) and co-morbid asthma and NP patients without asthma and to correlate these levels with clinical parameters of severity of disease. Forty NP patients (20 asthmatic and 20 nonasthmatic) were enrolled. Nasal secretion samples were collected from nasal cavities of all 40 subjects. The levels of Th1 cytokines IL-2, IL-12 and IFN-c, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, chemokine IL-8, and proinflammatory cytokines IL-1b, TNF-a and TNF-b were measured using flow cytometric method. Each of the 40 patients was staged clinically according to global nasal symptom score, endoscopic score, and Lund-Mackay computed tomography (CT) score. The concentrations of Th2 cytokines IL-5, IL-6 and IL-10 were significantly higher (P \ 0.01, P \ 0.01, P \ 0.05) in patients with NP and asthma compared with NP patients without asthma.Positive correlations were observed between concentration of IL-2 in nasal secretions and global nasal symptom score, endoscopic score, and Lund-Mackay score only in NP patients without asthma. We also found positive correlation between CT score and the levels of IL-8, IL-4, and IL-1b in nonasthmatic patients. Finally, our results showed a positive correlation between IL-5 levels in nasal fluid and endoscopic score only in asthmatic patients. NP in asthmatic patients have different immunological patterns compared to those without asthma. We also concluded that concentrations of cytokines measured in nasal fluid were not sensitive enough to determine the severity of disease.
Anesthetic agents could alter the course and outcome of physical trauma, as well as experimentally or naturally occurring severe infections, by regulating several immune response mechanisms. The aim of our study was to investigate the influence of several commercially used anesthetic agents (ketamine, propofole, pentylentetrazole - PTZ) on cytokine concentrations, animal survival and pathohistological changes in the model of rat sepsis. In adult, male Wistar rats after different anesthetic treatment and induction of sepsis by cecal ligation and punction we estimated serum levels of IL1α, TNFα, GM-CSF and MCP-1 at 12h intervals. After 48h of sepsis induction, the largest number of animals survived in the group treated with PTZ (47%), while the lowest survival rate was in the propofole treatment group (24%). Contrary to survival rate, the most abundant pathohistological changes were seen on preparations from PTZ and than in ketamine/PTZ treated groups, without any significant changes in the CNS of propofole treated animals. In the propofole treated group there was a prominent increament of GM-CSF values at 12h and 24h, followed by a significant decreament at 36h. These changes were negatively correlated to the survival rate in this group. This group had the lowest levels of MCP1 at all evaluated time intervals. After high initial levels, IL1α and TNFα levels fell to undetectable concentrations and at 24h increased to a high level. In PTZ as well as ketamine groups, at 12 h interval, GM-CSF levels were lower than in the propofole treated group. Contrary, MCP-1 levels were higher in these groups comparing to propofole group. After a high initial peak, IL1α levels decreased to low but detectable levels, followed by an intensive rise in ketamine treated, but with further decrement in pentazole treated groups. TNFα levels were low through all evaluated intervals in both these groups. Our results indicate that induction of anaesthesia of animals with sepsis with variuos anesthetic agents is connected to different pathohistological CNS changes, distinct serum cytokine profiles and diverse survival rates
BackgroundRecurrent pregnancy loss (RPL) affects up to 5% of pregnancies, but with no consensus on the definition. Inherited thrombophilia has been postulated as a risk factor for RPL. The aim of this study was to investigate the association of RPL with polymorphisms of five genes that influent the coagulation and fibrinolysis.MethodsThis study was conducted on total of 224 women, 129 women with ≥2 early RPL or ≥1 late pregnancy loss, 95 women with at least two normal life births and no history of pregnancy loss. Five gene polymorphisms F2 20 210G>A (rs1799963), F5 1691G>A (rs6025), MTHFR 677C>T (rs1801133), SERPINE1 −675 4G/5G (rs1799762) and ACE I/D (rs1799752) were genotyped by PCR-based methods.ResultsA significant relationship was found between SERPINE1 4G/4G and ACE D/D polymorphisms and RPL (p<0.001 both, OR 2.91 and 3.02, respectively). In contrast, no association was found between F2 20 210G>A, F5 1691G>A and MTHFR 677C>T polymorphisms and risk for RPL. A combination of hypofibrinolytic homozygotes SERPINE1 4G/4G+ACE D/D was observed as a highly associated with RPL (Cochran-Armitage test, p<0.001), and their strong independent association with RPL risk was confirmed by logistic regression analysis (both p values <0.001, OR 3.35 and 3.43, respectively).ConclusionOur data have demonstrated that SERPINE1 and ACE gene polymorphisms, individually or in combination, appear to be a significant risk for RPL. This data may be useful in adding to the knowledge on inherited thrombophilia as an important contributor to RPL pathogenesis.
Summary: Immunomodulatory treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) by macrolide antibiotics represents a challenging alternative to conventional therapy and surgery, still being at the very beginning. Immune and inflammatory processes in nasal and paranasal sinus mucosa, crucial in the etiopathogenesis of nasal polyps (NPs) are reflected in levels of various local mediators, found both in mucosa and nasal fluid. In this prospective study, we assessed the immunomodulatory and clinical effects of longterm low-dose oral macrolide treatment in the management of CRSwNP. Twenty-two (n = 22) nonasthmatic, nonallergic patients with CRSwNP were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory cytokines TNF-a, TNF-b, and IL-1b, Th1 cytokines IL-2, IL-12, and IFN-g, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using a flow cytometric method. We also scored each of the 22 patients before and after therapy according to Tsicopoulos' global nasal symptom score and Malm's endoscopic score. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-a (p<0.01) in nasal secretions. Macrolide therapy decreased the size of polyps in 45.45% of the patients. We concluded that long-term low-dose treatment with CAM was effective in the management of Kratak sadr`aj: Mada je u samim za~e cima, imunomo dulacijska terapija hroni~nog rinosinuzitisa sa nosnom poli pozom (HRSsNP) primenom makrolidnih anti biotika bi mogla predstavljati alternativu uobi~ajenoj konzer va tivnoj terapiji, kao i hirur{kom le~enju. Imunski i zapaljen ski procesi u sluzoko`i nosa i paranazalnih sinusa, naj zna ~ajniji u etiopato genezi nosnih polipa, reflektuju se na razli~ite lokalne medijatore, detektovane u sluzoko`i kao i u nosnom sekretu. U ovoj prospektivnoj studiji procenili smo imunomo dulacijske i klini~ke efekte dugotrajne niskodozirane oralne primene makrolidnog antibiotika u le~enju HRSsNP. Dva deset dvoje (n = 22) neastmati~nih, nealergi~nih pacijenata sa HRSsNP dobijalo je klaritromicin (CAM) u pojedina~noj dnevnoj dozi od 500 mg tokom osam nedelja. Merene su koncentracije proinflamatornih citokina TNF-a, TNF-b i IL-1b, Th1-cito kina IL-2, IL-12 i IFN-g, Th-2-citokina IL-4, IL-5, IL-6 i IL-10, kao i hemokina IL-8 u uzorcima nosnog sekreta, pre i nakon tera pije, primenom proto~ne citometrije. Svaki od pacijenata klini~ki je klasif i kovan pre i posle le~enja prema Tsicopoulosovom ukupnom nosnom simptom skoru i Malm-ovom endoskopskom skoru. Nakon le~enja, detektovane su znaajno ni`e koncentracije IL-8 (p<0,01) i TNF-a (p<0,01) u nosnom sekretu. Terapija makrolidnim antibio tikom je smanjila veli~inu polipa kod 45,45% od ukupnog bro ja paci jenata. Zaklju~eno je da je dugotrajna nisko dozirana primena
Background / Aim. Polymorphisms of the factor V Leiden (FV G1691A), factor II Prothrombin (FII G20210A) and methylenetetrahydrofolate reductase (MTHFR C677T) genes are the most commonly investigated inherited risk factors for developing venous thromboembolism (VTE). Despite this fact, there is insufficient data regarding their clinical burden and distribution in Montenegrin population. Consequently, the present study aimed to determine the frequency of these polymorphisms in Montenegrin patients with VTE. Methods. This case-control study was conducted on 160Caucasian subjects. The study group was composed of 80 patients (35 men and 45 women) with VTE. The control group consisted of 80 healthy individuals (32 men and 48 women), without previous thromboembolic episode. Genotyping of the FV G1691A, FII G20210A, and MTHFR C677T polymorphisms was performed by allele-specific polymerase chain reaction (PCR). Results. Our results demonstrated that the frequency of heterozygotes (HET) for FII G20210A and FV G1691A were significantly higher in VTE group compared to a healthy control group (χ2 = 11.7; p = 0.001 and χ2 = 17.69; p < 0.001respectively). This study confirmed the association of FII G20210A and FV G1691A polymorphisms with an increased risk of VTE (OR 10.5; 95 % CI = 2.34 to 47.27 and OR 14.8; 95 % CI = 3.34 to 65.43; p < 0.001respectively). Recessive homozygotes (RH) for FII G20210A and FV G1691A were not found in any of investigated group. As regarding MTHFR C677T, the difference between the frequency of HET and RH in the control and VTE group is not significant. Conclusion. Our study has shown that FII G20210A and FV G1691A polymorphisms are significantly associated with the VTE. Detection of above mentioned polymorphisms prior to VTE development can contribute to the prevention of further VTE occurrence, especially among patients' relatives who are carriers of these polymorphisms. Key words: venous thromboembolism, gene polymorphisms, FII G20210A, FV G1691А, MTHFR C677T. Apstrakt Uvod / Cilj. Polimorfizmi u genima koji kodiraju faktor V Leiden (FV G1691A), faktor II Protrombin (FII G20210A) i metilen tetrahidrofolat reduktazu (MTHFR C677T) su najčešće ispitivani nasledni faktori rizika za nastanak venskog tromboembolizma (VTE). Uprkos tome ne postoji dovoljno podataka o kliničkom značaju i distribuciji ovih polimorfizama u crnogorskoj populaciji. U skladu sa tim, cilj ove studije bio je da utvrdi frekvenciju ovih polimorfizama kod pacijenta sa venskim tromboembolizmom u Crnoj Gori. Metode. Studija: slučaj-kontrola. Istraživanje je sprovedeno na 160 ispitanika Kavkaskog porekla. Studijsku grupu sačinjavalo je 80 pacijenata (35 muškaraca i 45 žena) sa VTE, a kontrolna grupa se sastojala od 80 zdravih ispitanika (32 muškarca i 48 žena), koji nisu imali tromboembolijske epizode bolesti. Genotipizacija polimorfizama za: FV G1691A, FII G20210A i MTHFR C677T izvršena je alel specifičnom, lančanom reakcijom polimeraze. Rezultati. Rezultati ove studije su pokazali da je učestalost heterozigota (HET) za FII G20210A i ...
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