Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Passive smoking acutely affects the microcirculation in healthy non-smokers.

OBJECTIVE: Acute effects of passive smoking on microcirculation have not been sufficiently studied. The aim of the present study was to detect microcirculatory alterations in healthy non-smokers after passive exposure to cigarette smoke, utilizing the Near Infrared Spectroscopy method combined with the vascular occlusion technique. METHODS: Sixteen (9 females, age: 34 ±â€¯9 years) non-smoking, healthy volunteers were exposed to passive smoking for 30 min in a temperature-controlled environment. Smoke concentration was monitored with a real-time particle counter. The following microcirculatory parameters were estimated: baseline tissue oxygen saturation (StO2); StO2 decrement after vascular occlusion (indicating the oxygen consumption rate); StO2incremental response after vascular occlusion release (reperfusion rate); the time period where the StO2 signal returns to the baseline values after the hyperemic response. RESULTS: Baseline StO2 (79.6 ±â€¯6.4 vs. 79 ±â€¯8%, p = 0.53) as well as the time needed for StO2 to return to baseline levels (138.2 ±â€¯26.5 vs. 142.1 ±â€¯34.6 s, p = 0.64) did not significantly differ before vs. after passive smoking exposure. Oxygen consumption rate decreased after 30 min exposure to passive smoking (from 12.8 ±â€¯4.2 to 11.3 ±â€¯2.8%/min, p = 0.04); Reperfusion rate also significantly decreased (from 5.6 ±â€¯1.8 to 5 ±â€¯1.7%/s, p = 0.04). CONCLUSIONS: Our results suggest that acute exposure to passive smoking delays peripheral tissue oxygen consumption and adversely affects microcirculatory responsiveness after stagnant ischemia in healthy non-smokers.

-572 G/C single nucleotide polymorphism of interleukin-6 and sepsis predisposition in chronic renal disease.

Single nucleotide polymorphisms (SNPs) of interleukin (IL)-6 are associated with the development of chronic renal disease (CRD). Their impact for sepsis in the field of CRD was investigated. One control cohort of 115 patients with CRD without infection and another case cohort of 198 patients with CRD and sepsis were enrolled. Genotyping at the -174 (rs1800795) and -572 positions of IL-6 (rs1800796) was done by restriction fragment length polymorphism. Circulating IL-6 was measured by an enzyme immunoassay. The GG genotype of rs1800796 was more frequent among cases (78.3%) than controls (62.6%). No difference in the genotype frequencies of rs1800795 between cases and controls were found. Odds ratio for sepsis was 2.07 (95%CI 1.24-3.44, p = 0.005) with the GG genotype of rs1800796, which was confirmed by logistic regression analysis taking into consideration the presence of chronic comorbidities. All-cause mortality until day 28 was similar between patients with the GG genotype and the GC/CC genotypes of rs1800796, but death caused from cardiovascular events not-related with infection was more frequent with the GG genotype (14.6% vs 2.4%, p = 0.031). Circulating IL-6 was greater among patients of the GC/CC genotypes of rs1800796 and multiple organ dysfunction (p = 0.013). The GG genotype of rs1800796 predisposes to sepsis in CRD and to 28-day mortality by sepsis-unrelated cardiovascular phenomena.

"Bath Salts" intoxication with multiorgan failure and left-sided ischemic colitis: a case report.

BACKGROUND: In the recent years, a new group of designer drugs, under the brand name of bath salts has emerged as a new trend. They are mainly b-ketone amphetamine analogs and are derivatives of cathinone, a monoamine alkaloid. They are abused for psychostimulant effects. Their primary ingredient 3,4-methylenedioxypyrovalerone (MDPV), has alerted authorities worldwide due to its severe physiological and behavioral toxicities. Description of Case:We present the case of a 47-year-old man with coma, seizures, multi-organ failure and ischemic colitis after intoxication with bath salts containing MDPV. After supportive care, he had a successful outcome. To our knowledge, this report is the first to describe ischemic colitis after MDPV intoxication. Clinicians need to be especially alert since MDPV is not detected by routine screens, and its overdose can be life-threatening. CONCLUSION: Ischemic colitis should be recognized as a potential complication of bath salts ingestion in order to prevent unnecessary interventions, such as diagnostic laparotomy, which could worsen patient's condition. Hippokratia 2015; 19 (4): 363-365.

A case of imported Middle East Respiratory Syndrome coronavirus infection and public health response, Greece, April 2014.

On 18 April 2014, a case of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection was laboratory confirmed in Athens, Greece in a patient returning from Jeddah, Saudi Arabia. Main symptoms upon initial presentation were protracted fever and diarrhoea, during hospitalisation he developed bilateral pneumonia and his condition worsened. During 14 days prior to onset of illness, he had extensive contact with the healthcare environment in Jeddah. Contact tracing revealed 73 contacts, no secondary cases had occurred by 22 April.

Breath markers of oxidative stress and airway inflammation in Seasonal Allergic Rhinitis.

Oxidative stress (OS) is well documented in asthma, but so far, little data has been reported in nonasthmatic patients with Seasonal Allergic Rhinitis (SAR). The aim of this study is to investigate the degree of OS and airway inflammation in patients with SAR, with and without concomitant asthma (SAR+A), using breath markers in exhaled air and in Exhaled Breath Condensate (EBC). In addition, the effects of natural allergen exposure and intranasal steroid treatment on these markers were evaluated. Exhaled NO (eNO) and CO, combined with measurements of 8-Isoprostane (Iso-8), Leukotriene B4 (LTB4) and nitrate/nitrite in EBC, were performed in 23 patients, 11 with SAR and 12 with SAR+A, and 16 healthy subjects. Iso-8 and LTB4 were significantly increased in both groups of patients (median values 43.6 pg/ ml and 138.4 pg/ml in SAR group; 38.9 pg/ml, and 164.6 pg/ml in SAR+A group respectively; p>0.05) compared to healthy subjects (18.6 pg/ml and 7.8 pg/ml; p<0.05). Nitrate/nitrite and eNO levels were elevated in both groups compared to controls, but were significantly higher in the SAR+A compared to SAR group (nitrate/nitrite 9 microM and 3.9 microM; p=0.025; and eNO 18.5 ppb and 12.5 ppb, respectively; p>0.05). Nasal steroids caused significant reduction in LTB4 and 8-isoprostane levels in both groups of patients (p<0.05), while nitrate levels and eNO concentration were little affected by nasal treatment. OS markers were decreased at normal levels out of pollen season. Natural allergen exposure induces OS and airway inflammation, as assessed by measurements of markers in EBC and exhaled air, in patients with SAR who have no clinical signs of lower airway involvement. Besides, intranasal steroid treatment may have a regulatory role in the OS.

Exhaled nitric oxide in seasonal allergic rhinitis: influence of pollen season and therapy.

Exhaled nitric oxide (eNO) has been proposed as a potential indirect marker of lower airway inflammation in asthma. To investigate the existence of lower airways inflammation in allergic rhinitis eNO measurements were performed in 32 patients with symptomatic and asymptomatic seasonal allergic rhinitis early in and out of pollen seasons and in 80 healthy volunteers. To further define how exhaled NO is modified by therapy, NO levels were detected following 1-month treatment with either inhaled steroids or non-steroids therapy with nedocromil. Exhaled NO (mean +/- SE) was significantly elevated in patients with seasonal allergic rhinitis with and without symptoms (24.2 + 2.5 and 13.9 + 2.9 ppb, respectively) as compared to healthy volunteers (4.5 + 0.3 ppb) both in and out of pollen season (21.2 + 2.1 and 9.0 + 1.4 p.p.b., respectively) with a higher increase during the allergen exposure in season. Higher levels of exhaled NO were detected in patients with symptoms, either from the upper or lower airways, and with bronchial hyperreactivity. The increased exhaled NO in symptomatic patients was reduced only by inhaled steroids and not by nedocromil. These findings possibly suggest the existence of lower airway inflammation in both symptomatic and asymptomatic patients with seasonal allergic rhinitis in and out of pollen season. Thus, exhaled NO may be used as a non-invasive index for early detection of lower airway inflammation and for monitoring the optional treatment in patients with seasonal allergic rhinitis.

Effects of laparoscopic cholecystectomy on global respiratory muscle strength.

Laparoscopic cholecystectomy has a better postoperative outcome than the traditional open technique, which has been shown to significantly affect respiratory muscle function. The aim of this study was to investigate the effects of laparoscopic surgery on respiratory function, and particularly that of the respiratory muscles. Respiratory muscle strength was assessed in 26 patients who underwent laparoscopic cholecystectomy and in 25 who underwent open cholecystectomy by measuring mouth pressure during maximum static inspiratory (PImax) and expiratory (PEmax) efforts. PImax, PEmax, and blood gases were measured 24 h preoperatively (-24 h) as well as 24 h (+24 h) and 48 h (+48 h) postoperatively. FEV1 and FVC were measured at -24 h and +48 hr, and the ratio of FEV1 to FVC (FEV1/FVC) was calculated. PImax decreased at +24 h and +48 h in both groups, but this decrease was significantly greater in the patients who had open surgery, (p < 0.01, and p < 0.005, respectively). Similarly, PEmax was significantly smaller in the open- than in the laparoscopic-surgery group (p < 0.0001) at +48 h. Spirometric indices showed a more severe restrictive defect at +48 h after open surgery than after laparoscopy (p = 0.01). The arterial oxygen tension (PaO2) was significantly greater in the laparoscopic- than in the open-surgery group at +24 h (p < 0.007). Laparoscopic cholecystectomy caused smaller decreases in respiratory muscle strength than did open surgery. This accords with the hypothesis of phrenic nerve inhibition during open surgery. The results are of clinical importance, since they may explain the different outcomes with the two techniques.