Grzegorz Oszkinis

Angiotensin-converting enzyme (ACE, I/D) gene polymorphism and susceptibility to abdominal aortic aneurysm or aortoiliac occlusive disease.

BACKGROUND The purpose of this study was to examine the role of polymorphism in angiotensin converting enzyme gene (ACE, I/D) in the development of abdominal aortic aneurysm (AAA) or aortoiliac occlusive disease (AIOD). MATERIALS AND METHODS We investigated 829 individuals in 4 groups: AAA (n = 133), AIOD (n = 152), control (n = 152), and a random Polish population group (n = 392). ACE I/D gene polymorphism analysis was performed by polymerase chain reaction and gel electrophoresis. The genotype distribution was in Hardy-Weinberg equilibrium. RESULTS The genotype distribution and allele frequency of ACE I/D were not significantly different between patients with AAA or AIOD and the control or the population group. Significant differences were found between the following groups: 1) hypertensive patients with AAA and normotensive patients with AAA (OR = 3.08 95% CI 1.22-7.79, P = 0.0147); 2) hypertensive patients with AAA and the population group (OR = 2.56; 95% CI 1.27-5.16, P = 0.0066). Since the majority of subjects were male, these associations were also true when only male hypertensive subjects with AAA were compared with male normotensive patients with AAA or to male population group. No relation of the ACE gene polymorphism to hypertension in the AIOD group was found. CONCLUSIONS ACE I/D gene polymorphism is not a susceptibility factor to aortoiliac occlusive disease; however it may be an important factor in the development of AAA when coexisting with hypertension.

The influence of genetic polymorphism of Cyp2c19 isoenzyme on the pharmacokinetics of clopidogrel and its metabolites in patients with cardiovascular diseases

An extensive investigation on pharmacokinetics of clopidogrel and its metabolites as well as pharmacodynamics of the drug was performed in patients with cardiovascular disease carrying various alleles coding CYP2C19 isoenzyme. The influence of non‐genetic factors on the clopidogrel response was also studied. Plasma concentrations of clopidogrel, its carboxylic metabolite, and diastereoisomers of a thiol metabolite (the inactive H3 and the active H4) following an administration of 75 mg of the drug were determined in three groups of patients divided with respect to their CYP2C19 genotype: ultrametabolizers, extensive metabolizers, and intermediate metabolizers. The mean peak plasma concentration of H4 in intermediate metabolizers was 3.1‐ and 2.8‐fold lower than that of ultrametabolizers (P = 0.055) and extensive metabolizers (P = 0.026), respectively. The mean H4 area under the curve (AUC0–24 h) for intermediate metabolizers were significantly lower than that for ultrametabolizers (P = 0.046). Intermediate metabolizers exhibited a significantly higher platelet aggregation than ultrametabolizers and extensive metabolizers (P = 0.035). A multivariate analysis showed that the effect of CYP2C19*2 allele on an ADP‐induced platelet aggregation was better pronounced in the presence of non‐genetic risk factors (P = 0.008).

Current options in prosthetic vascular graft infection: comparative analysis of 63 consecutive cases

PurposeThe study was conducted to compare the results of two different techniques of vascular reconstruction in patients after the removal of infected vascular prostheses.MethodsSixty-three patients with vascular prostheses infections underwent treatment. Either the infected fragments or the entire prosthesis was removed in all of the patients. Extra-anatomical grafts were implanted in 19 cases. Cryopreserved allogenic arterial grafts were applied for reconstruction in 44 patients.ResultsIn a 19-patient group with extra-anatomical grafts, two patients died (10.5%). In seven patients (36.8%) relapse symptoms of infection appeared. Primary and secondary patencies of the grafts after 3 years were 31.6% and 52.6% respectively. In a group of 44 patients with allogenic grafts no recurrence of infection was observed. Six patients died (13.6%). Primary and secondary patencies after 3 years were 63.6% and 81.8% respectively.ConclusionsThe results reveal the benefits of the allogenic arterial grafts in revascularization in patients with major vascular prostheses infections. The differences in secondary patencies of the implanted allogenic grafts indicate the necessity of an early selection of patients for the complete removal of the infected prosthesis, during a time when patients are in general good health.

Risk factors in abdominal aortic aneurysm and in Polish population aortoiliac occlusive disease and differences between them [corrected].

Abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD) are multifactorial vascular disorders caused by complex genetic and environmental factors. The purpose of this study was to define risk factors of AAA and AIOD in the Polish population and indicate differences between diseases.

Capillary Zone Electrophoresis method for determination of (+)-S clopidogrel carboxylic acid metabolite in human plasma and urine designed for biopharmaceutic studies

Fast and reproducible Capillary Zone Electrophoresis (CZE) method for the quantification of (+)-S clopidogrel carboxylic acid metabolite in human fluids was elaborated for the first time. Optimal buffer and CZE conditions were established to obtain the complete separation of clopidogrel, its metabolite and piroxicam (internal standard), during one analytical run. Finally, resolution of the analytes was obtained in an uncoated silica capillary filled with a phosphate buffer of pH 2.5. The analytes were isolated from plasma and urine samples using solid phase extraction (SPE). Validation of the CZE method was carried out. The calibration curve of clopidogrel was linear in the range of 0.5-10.0mg/L in plasma and urine, whereas for (+)-S carboxylic acid metabolite linearity was confirmed in the range of 0.25-20.0mg/L in plasma and 0.25-10.0mg/L in urine. Intra- and inter-day precision and accuracy were repeatable. LOD and LOQ were also estimated. SPE recovery of the analytes from plasma and urine was comparable and greater than 80%. The validated method was successfully applied in pharmacokinetic investigations of (+)-S carboxylic acid metabolite of clopidogrel following the oral administration of clopidogrel to patients prior to percutaneous coronary intervention.

Comparison of Superb Micro-Vascular Ultrasound Imaging (SMI) and Contrast-Enhanced Ultrasound (CEUS) for Detection of Endoleaks After Endovascular Aneurysm Repair (EVAR).

Patient: Male, 68 Final Diagnosis: Unusual clinical course Symptoms: None Medication: — Clinical Procedure: Angio CT Specialty: Surgery Objective: Challenging differential diagnosis Background: High-resolution contrast-enhanced ultrasound is one of methods used in the detection and characterization of endoleaks, which is a frequent complication after EVAR. A new technology provided by Toshiba’s AplioTM 500 ultrasound system, called Superb Micro-Vascular Imaging (SMI), is dedicated specifically to imaging very low flow states and appears to be a promising new method for detection of endoleaks. Case Report: After endovascular treatment, a 68-year-old patient who had stent-graft implantation underwent clinical examinations, including contrast-enhanced ultrasound (CEUS), superb micro-vascular imaging (SMI), and computed tomographic angiography (CTA), revealing additional information about abnormal blood flow localized in the periphery of the sack of the left common iliac artery aneurysm. By using CEUS and SMI, the endoleak was clearly visible. Conclusions: This case report illustrates the potential clinical value of this advanced Doppler technology (SMI) and how it could influence clinical management.

Polymorphisms of genes involved in the hypoxia signaling pathway and the development of abdominal aortic aneurysms or large-artery atherosclerosis

BACKGROUND The pathogenesis of aortic diseases, both aneurysmal and occlusive, is associated with the occurrence of local ischemic/hypoxic conditions, but the genetic factors that differentiate the predisposition to specific types of aortic diseases are largely unknown. In this study, the functional variants in genes involved in the hypoxia signaling pathway, hypoxia-inducible factor-1α (HIF1A) 1772C>T, 1790G>A, and vascular endothelial growth factor (VEGFA) -634G>C, were analyzed in search of the associations specific to abdominal aortic aneurysm (AAA) development. METHODS The study encompassed a series of 518 patients with AAA, 354 patients with aortoiliac occlusive disease, and 541 controls. In AAA patients, the occurrence of peripheral arterial disease (PAD) was examined with duplex arterial scanning. Genotypes were determined by the polymerase chain reaction/restriction fragment length polymorphism method or with TaqMan probes. RESULTS In univariate analysis, a significantly increased risk for development of AAA without coexisting PAD was found in VEGFA -634C allele carriers (effect of allele dose: odds ratio [OR], 1.38; P = .012). In VEGFA -634CC homozygotes, the risk was enhanced by the interaction with HIF1A 1772CC-1790GG genotype (OR, 2.41; P = .008). This joint effect of homozygous genotypes also influenced the AAA risk independently of PAD coexistence (OR, 1.87; P = .036). In contrast, the minor allele of the HIF1A 1772C>T polymorphism (1772T and 1772T-1790G haplotype) was significantly associated with the occurrence of AAA with concomitant PAD (OR, 2.02; P = .009 for the dominant model). This effect was enhanced in the VEGF -634GG homozygotes (OR, 2.86; P = .005) and among smokers (OR, 3.10; P = .001). The individual effects of the HIF1A 1772 and VEGFA -634 polymorphisms on AAA risk remained significant in multivariable analysis after adjustment for the traditional vascular risk factors and analyzed polymorphisms. None of the studied variants influenced the risk of aortoiliac occlusive disease. CONCLUSIONS This study identifies polymorphisms in the HIF1A and VEGF genes as potential genetic markers that indicate the predisposition to either AAA coexisting with peripheral atherosclerosis or AAA without such lesions, suggesting the genetic heterogeneity of this disease. The HIF1A 1772T allele also seems to be a genetic risk factor that determines sensitivity to cigarette smoke exposure. Further work is needed to confirm the findings in an independent samples set and to study the functional role of studied variants in AAA.

SEPP1 gene variants and abdominal aortic aneurysm: gene association in relation to metabolic risk factors and peripheral arterial disease coexistence

An inadequate selenium level is supposed to be a risk factor for cardiovascular diseases. However little is known about variation of the genes encoding selenium-containing proteins that would confirm the causality in these diseases. The aim of this study was to analyze the relationships between two functional variants of selenoprotein P gene (SEPP1 rs3877899G>A, rs7579G>A) and the occurrence of abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD), as well as their metabolic risk factors. In AAA, the rs3877899A allele was associated with higher systolic blood (P < .003) and pulse pressure (P < .003) values (recessive model), and with coexistence of peripheral arterial disease (PAD; carriers: P = .033). The other SEPP1 variants were associated with BMI values and influenced the risk of aortic diseases, depending on body weight. The strongest associations in the case-control analysis was found between the presence of the rs3877899G-rs7579G haplotype and development of AAA in overweight and obese subjects (OR = 1.80, 95%CI = 1.16–2.79, P = .008). The higher BMI values were correlated with lower age of AAA patients and larger size of aneurysm. Our results suggests the potential role of the selenoprotein P in pathogenesis of AAA. Future studies should consider the role of the rs3877899G-rs7579G haplotype as a risk factor for aggressive-growing AAAs.

Stent-graft treatment of extracranial internal carotid artery aneurysm

Extracranial internal carotid artery aneurysm is not a frequent finding. Although there are a number of methods used for the treatment of this kind of pathology, every approach should be tailored to the patient. The authors describe the case of a patient with a large extracranial internal carotid artery aneurysm presenting as a tumor of the parapharyngeal space, treated with a stent-graft. The patient remains asymptomatic at the 2-year follow-up. To our knowledge, this type of successful treatment of a carotid aneurysm has been reported only once so far.

Combined surgical-endovascular treatment of multiple splenic artery aneurysms.

Accepted: 24 May 2004 Published online: 28 July 2004