Oscillometric measurement of the ankle-brachial index and the estimated carotid-femoral pulse wave velocity improves the sensitivity of an automated device in screening peripheral artery disease.

Background and aims: To overcome the time and personnel constraints of the Doppler method, automated, four-limb blood pressure monitors were recently developed. Their additional functions, such as measuring the estimated carotid-femoral pulse wave velocity (ecfPWV), have been, thus far, less studied. We aimed to compare the sensitivity and specificity of different ankle-brachial index (ABI), toe-brachial index (TBI), and ecfPWV measurement methodologies to evaluate their contribution to peripheral artery disease (PAD) screening. Methods: Among 230 patients (mean age 64 ± 14 years), ABI measurements were performed using a Doppler device and a manual sphygmomanometer. The Doppler ABI was calculated by taking the higher, while the modified Doppler ABI by taking the lower systolic blood pressure of the two ankle arteries as the numerator, and the higher systolic blood pressure of both brachial arteries as the denominator. The automated ABI measurement was carried out using an automatic BOSO ABI-system 100 PWV device, which also measured ecfPWV. TBI was obtained using a laser Doppler fluxmeter (Periflux 5000) and a photoplethysmographic device (SysToe). To assess atherosclerotic and definitive PAD lesions, vascular imaging techniques were used, including ultrasound in 160, digital subtraction angiography in 66, and CT angiography in four cases. Results: ROC analysis exhibited a sensitivity/specificity of 70.6%/98.1% for the Doppler ABI (area under the curve, AUC = 0.873), 84.0%/94.4% for the modified Doppler ABI (AUC = 0.923), and 61.5%/97.8% for the BOSO ABI (AUC = 0.882) at a cutoff of 0.9. Raising the cutoff to 1.0 increased the sensitivity of BOSO to 80.7%, with the specificity decreasing to 79.1%. The ecfPWV measurement (AUC = 0.896) demonstrated a 63.2%/100% sensitivity/specificity in predicting atherosclerotic lesions at a cutoff of 10 m/s. Combining BOSO ABI and ecfPWV measurements recognized 89.5% of all PAD limbs. Conclusion: The combined BOSO ABI and ecfPWV measurements may help select patients requiring further non-invasive diagnostic evaluation for PAD. The user-friendly feasibility may make it suitable for screening large populations.

Screening for Peripheral Artery Disease Using an Automated Four-Limb Blood Pressure Monitor Equipped with Toe-Brachial Index Measurement.

Toe-brachial index (TBI) measurement helps to detect peripheral artery disease (PAD) in patients with incompressible ankle arteries due to medial arterial calcification, which is most frequently associated with diabetes. We aimed to evaluate how an automated four-limb blood pressure monitor equipped with TBI measurement could contribute to PAD screening. In 117 patients (mean age 63.2 ± 12.8 years), ankle-brachial index (ABI) measurement was performed using the Doppler-method and the MESI mTablet. TBI was obtained via photoplethysmography (MESI mTablet, SysToe) and a laser Doppler fluxmeter (PeriFlux 5000). Lower limb PAD lesions were evaluated based on vascular imaging. A significant correlation was found between Doppler and MESI ankle-brachial index values (r = 0.672), which was stronger in non-diabetic (r = 0.744) than in diabetic (r = 0.562) patients. At an ABI cut-off of 0.9, Doppler (AUC = 0.888) showed a sensitivity/specificity of 67.1%/97.4%, MESI (AUC 0.891) exhibited a sensitivity/specificity of 57.0%/100%; at a cut-off of 1.0, MESI demonstrated a sensitivity/specificity of 74.7%/94.8%. The TBI values measured using the three devices did not differ significantly (p = 0.33). At a TBI cut-off of 0.7, MESI (AUC = 0.909) revealed a sensitivity/specificity of 92.1%/67.5%. Combining MESI ABI and TBI measurements recognised 92.4% of PAD limbs. Using an ABI cut-off level of 1.0 and sequential TBI measurement increases the sensitivity of the device in detecting PAD. The precise interpretation of the obtained results requires some expertise.

Examination of Lower Limb Microcirculation in Diabetic Patients with and without Intermittent Claudication.

Intermittent claudication is a frequent complaint in lower extremity artery disease, but approximately two thirds of patients are asymptomatic, most of which are diabetic patients. Non-invasive angiological and microrheological tests on diabetic subjects with and without intermittent claudication were performed in the present study. In total, 98 diabetic patients were included and divided into two groups: 20 patients (63.5 ± 8.8 years, 55% men, 45% women) had intermittent claudication, 78 patients (65.5 ± 9.3 years, 61.5% men, 38.5% women) were asymptomatic. Hand-held Doppler ultrasound examination, transcutaneous tissue partial oxygen pressure (tcpO2) measurement, Rydel-Seiffer tuning fork tests, and 6-min walk tests were performed, and erythrocyte aggregation was investigated. Ankle-brachial index (p < 0.02) and tcpO2, measured during provocation tests (p < 0.003) and the 6-min walk test (p < 0.0001), significantly deteriorated in the symptomatic group. A higher erythrocyte aggregation index and faster aggregate formation was observed in claudication patients (p < 0.02). Despite the statistically better results of the asymptomatic group, 13% of these patients had severe limb ischemia based on the results of tcpO2 measurement. Claudication can be associated with worse hemodynamic and hemorheological conditions in diabetic patients; however, severe ischemia can also develop in asymptomatic subjects. Non-invasive vascular tests can detect ischemia, which highlights the importance of early instrumental screening of the lower limbs.

Disease-Specific Quality of Life among Patients with Peripheral Artery Disease in Hungary.

Peripheral artery disease (PAD) is a progressive atherosclerotic disease significantly impacting functional status and health-related quality of life (HRQoL). This study aimed to investigate HRQoL among PAD patients in Hungary using the validated Hungarian version of the PADQoL questionnaire. Patients with symptomatic PAD were consecutively recruited from the Department of Angiology, Clinical Center, University of Pécs, Hungary. Demographics, risk factors, and comorbidities were registered. Disease severity was measured by Fontaine and WIFI stages. Descriptive statistical analysis, Chi-square test, and non-parametric tests were performed (p < 0.05). Overall, 129 patients (mean age 67.6 ± 11.9 years, men 51.9%) participated in our study. The Hungarian PADQoL demonstrated good internal consistency (α range: 0.745-0.910). Factors on intimate and social relationships gave the best (89.15 ± 20.91; 63.17 ± 26.05) and sexual function (28.64 ± 27.42), and limitations in physical functioning (24.68 ± 11.40) the worst scores. PAD had a significant negative impact on the social relationships of patients aged 21-54 years (51.6 ± 25.4). Fontaine stage IV patients experienced significantly lower HRQoL due to fear and uncertainty (46.3 ± 20.9) and limited physical functioning (33.2 ± 24.8). The Hungarian PADQoL identified central aspects of HRQoL. Advanced PAD was found to impact several areas of HRQoL, primarily physical functioning and psycho-social well-being, drawing attention to the importance of early diagnosis and management.

Hemizygous nonsense variant in the moesin gene (MSN) leads to a new autoimmune phenotype of Immunodeficiency 50.

Here, we present the findings of an investigation involving two male siblings with juvenile total tooth loss, early-onset chronic leg ulcers, and autoimmune thyroiditis, as well as focal segmental glomerulosclerosis with associated pulmonary emphysema in one and diabetes mellitus in the other. The clinical picture and lupus anticoagulant, cryoglobulin, and cold agglutinin positivity suggested the diagnosis of antiphospholipid syndrome. Flow cytometry analysis showed immunophenotypes consistent with immune dysregulation: a low number of naive T cells, elevated CD4+ T cell counts, and decreased CD8+ T-cell counts were detected, and more than half of the T-helper population was activated. Considering the siblings' almost identical clinical phenotype, the genetic alteration was suspected in the background of the immunodeficiency. Whole exome sequencing identified a previously not described hemizygous nonsense variant (c.650G>A, p.W217X) within exon 6 of the moesin (MSN) gene localized on chromosome X, resulting in significantly decreased MSN mRNA expression compared to healthy controls. We present a putative new autoimmune phenotype of Immunodeficiency 50 (MIM300988) characterized by antiphospholipid syndrome, Hashimoto's thyroiditis, leg ulcers, and juvenile tooth loss, associated with W217X mutation of the MSN gene.

Hemorheological Parameters in Diabetic Patients: Role of Glucose Lowering Therapies.

Diabetes mellitus influences several important hemorheological parameters including blood viscosity, erythrocyte aggregation and deformability. In the present study, 159 type-2 diabetic patients and 25 healthy controls were involved. Patient's age, body weight, body mass index (BMI), smoking habits, physical activity, history of cardiovascular diseases, current antidiabetic therapy and concomitant medication were recorded. Patients were grouped according to their antidiabetic treatment with insulin, or with one or more of the following antidiabetic drugs: metformin, sulfonylureas, acarbose, or no antidiabetic therapy. Hemorheological measurements (hematocrit, erythrocyte aggregation, plasma fibrinogen, whole blood and plasma viscosity), von Willebrand factor activity, and platelet aggregation measurements were performed. Platelet aggregation was investigated with the method of Born. Plasma viscosity and red blood cell aggregation were significatly higher in diabetes. No significant difference was found in hemorheological parameters between different antidiabetic regimens. Whole blood and plasma viscosity and red blood cell aggregation correlated with glucose levels but not with HbA1C levels. In conclusion, plasma and whole blood viscosity, as well as red blood cell aggregation appear to be associated with concurrent hyperglycemia, but not with the quality of glycemic control or the applied antidiabetic treatment. Platelet aggregation induced by ADP or epinephrine does not seem to be associated with diabetes even at subthreshold doses.

Hungarian adaptation of the Peripheral Artery Disease Quality of Life questionnaire / A perifériás veroérbetegek életminoségét vizsgáló angol nyelvu kérdoív magyar adaptálása.

Összefoglaló. Bevezetés: A perifériás veroérbetegség napjaink egyik világméretu népegészségügyi problémája, több mint 200 millió embert érint világszerte. A Peripheral Artery Disease Quality of Life (PADQOL) kérdoívet azzal a céllal fejlesztették ki, hogy a betegség fizikai tünetein kívül annak szubjektív betegségterhét, pszichoszociális és emocionális hatásait is vizsgálja. Célkituzés: Az eredeti, angol nyelvu PADQOL betegségspecifikus, önkitöltos kérdoív magyar nyelvu, érvényes változatának kifejlesztése, annak fordítása, kultúrközi adaptációja és magyar nyelvi validálása. Módszerek: Az életminoség-kérdoív lingvisztikai validálása nemzetközi protokoll alapján történt: két szakfordító külön-külön lefordította a kérdoívet angol forrásnyelvrol magyarra; egy harmadik szakfordító bevonásával elkészült a két verzió szintézise, majd azt két, angol anyanyelvu fordító visszafordította angol forrásnyelvre, amit konszenzusmegbeszélés követett. A "pre-final" magyar verzió érthetoségét 30, angiológiai járó és fekvo beteg bevonásával, kognitív interjúk lefolytatásával, pilotvizsgálat során teszteltük. A PADQOL kérdoív faktorstruktúrájának feltárásához faktoranalízist végeztünk, az alskálák megbízhatóságát, a tételek belso konzisztenciáját a Cronbach-alfa-együttható kiszámításával vizsgáltuk. Az elemzésekhez IBM SPSS 23.0 programcsomagot használtunk. Eredmények: A PADQOL nyelvi validálása jelentéstani, tapasztalati és idiomatikus ekvivalencia tekintetében nem jelentett nehézséget. A kognitív interjúk során egy kérdés esetén tapasztaltunk értelmezési nehézséget. A kérdoív "pre-final" verziója tartalmilag és nyelvileg könnyen értheto, kitöltése nem okoz nehézséget. Az egyes dimenziók Cronbach-α-értéke 0,624 és 0,887 között volt. A legrosszabb értéket a Félelem és bizonytalanság (score-átlag: 14,07) életminoség-dimenzió mutatta. Következtetés: Létrehoztuk a PADQOL kérdoív végso magyar verzióját, mely méroeszköz alkalmas a nyelvi és kultúrközi adaptáció következo lépésének elvégzésére, nagyobb betegpopuláción történo pszichometriai és klinikometriai vizsgálat által a perifériás veroérbetegek életminoségének, szubjektív betegségterhének felmérését célzó validálásra. Orv Hetil. 2020; 161(51): 2153-2161. INTRODUCTION: Peripheral artery disease is one of the greatest, global public health concerns affecting more than 200 million people worldwide. The Peripheral Artery Disease Quality of Life questionnaire was developed to assess the subjective disease burden of peripheral artery disease, by focusing on psychosocial and emotional effects besides physical symptoms and functional limitations. OBJECTIVE: To develop the valid Hungarian version of the original PADQOL via the standard linguistic validation and cross-cultural adaptation procedure. METHODS: The linguistic validation was conducted according to an international protocol: two independent forward translations, a synthesis of the translations, back translations and consensus team review. The pilot-testing of the 'pre-final' Hungarian version was conducted via cognitive interviews with 30 in- and outpatients attending the Department of Angiology. Factor analysis was performed, Cronbach-alpha values were calculated to establish the reliability of subscales and to determine the internal consistency if items. IBM SPSS 23.0 was used. RESULTS: The linguistic validation of PADQOL into Hungarian posed no difficulties in terms of semantic, experiential and idiomatic equivalence. One item was found difficult to interpret during cognitive interviewing. The 'pre-final' version of the questionnaire was easy to understand and complete. Cronbach-alpha values of factors ranged between 0.624 and 0.887. The lowest value was that of factor 4: Fear and Uncertainty (mean score: 14.07). CONCLUSION: The linguistic validation of PADQOL into Hungarian was successful, the final Hungarian version is a tool that should reveal valuable insights with regard to subjective disease burden of patients living with peripheral artery disease subsequent to psychometric and clinicometric validation on a larger patient population. Orv Hetil. 2020; 161(51): 2153-2161.

Characteristics of Patients Referred To A Specialized Headache Clinic.

Headache is a common problem with great effect both on the individual and on the society. Recent studies raised the possibility of increasing rate of specialty referrals, inappropiate treatment and advanced imaging for simple headache. The aim of our study was to analyze the characteritics of patients (including duration of symptoms, headache type, brain imaging, treatment) referred to our specialized headache clinic between 01/01/2014 and 01/01/2015 by their general practitioners and primary care neurologists due to chronic/treatment-resistant headache syndromes. 202 patients (mean age 53.6 ± 17.6 years) were evaluated in our clinic (102 females, mean age 50.14 ± 16.11 years and 100 males, mean age 57 ± 18.1 years). Migraine (84/202) and tension-type (76/202) were the most common syndromes. 202 plain brain CT, 60 contrast-enhanced CT and 128 MRI were carried out by their general practitioners or other healthcare professioners including neurologists before referral to our headache centre. Despite of extensive brain imaging appropiate treatment was started less than 1/3 of all patients and significant proportion received benzodiazepines or opioid therapy. Furthermore, more than 10% of referred patients presented with secondary headache including one meningitis. The management of headache is still a challenge for primary care physicians leading to medical overuse. Vast majority of our patients should not be referred to our specialized headache clinic as they had uncomplicated headache or other underlying conditions than pain.

Early seizures after ischemic stroke: focus on thrombolysis.

INTRODUCTION: Stroke is a significant underlying cause of epilepsy. Seizures due to ischemic stroke (IS) are generally categorized into early seizures (ESs) and late seizures (LSs). Seizures in thrombolysis situations may raise the possibility of other etiology than IS. AIM: We overtook a systematic review focusing on the pathogenesis, prevalence, risk factors, detection, management, and clinical outcome of ESs in IS and in stroke/thrombolysis situations. We also collected articles focusing on the association of recombinant tissue-type plasminogen activator (rt-PA) treatment and epileptic seizures. RESULTS: We have identified 37 studies with 36,775 participants. ES rate was 3.8% overall in patients with IS with geographical differences. Cortical involvement, severe stroke, hemorrhagic transformation, age (<65 years), large lesion, and atrial fibrillation were the most important risk factors. Sixty-one percent of ESs were partial and 39% were general. Status epilepticus (SE) occurred in 16.3%. 73.6% had an onset within 24 h and 40% may present at the onset of stroke syndrome. Based on EEG findings seizure-like activity could be detected only in approximately 18% of ES patients. MRI diffusion-weighted imaging and multimodal brain imaging may help in the differentiation of ischemia vs. seizure. There are no specific recommendations with regard to the treatment of ES. CONCLUSION: ESs are rare complications of acute stroke with substantial burden. A significant proportion can be presented at the onset of stroke requiring an extensive diagnostic workup.

Lower limb ischemia and microrheological alterations in patients with diabetic retinopathy.

BACKGROUND: Diabetes mellitus is frequently associated with vascular pathologies and hemorheological disorders. METHODS: 105 patients with diabetic retinopathy (DRP) (mean age 64.64±9.01 years, 56 males, 49 females), 35 age-matched non-diabetic (mean age 61.65±7.6 years, 14 males and 21 females) and 42 young healthy volunteers (mean age 25.52±3.32 years, 22 males, 20 females) were recruited. Lower extremity artery disease (LEAD) and microcirculatory alterations were screened by hand-held Doppler, transcutaneous partial tissue oxygen tension (tcpO2), tuning fork test, 6-minute walk test, erythrocyte aggregation and deformability. RESULTS: High prevalence of LEAD was detected in diabetic population: 55.3% fulfilled the criteria of LEAD based on ankle-brachial index; severely impaired tcpO2 was measured in 18.6%. The results of non-invasive measurements of the diabetic patients were significantly worse than those of the control groups (p < 0.05). Hemorheological disturbances could be characterized by the significantly higher erythrocyte aggregation (p < 0.05) and lower erythrocyte deformability (p < 0.05) in the diabetic population. CONCLUSION: Macro- and microcirculatory lower limb disorders could be revealed at high prevalence in diabetic patients with retinopathy. Measurement of tcpO2 and hemorheological variables could be useful to discover patients at higher risk for diabetic foot complications.

Toe-brachial index and exercise test can improve the exploration of peripheral artery disease.

BACKGROUND AND AIMS: We assumed that hand-held Doppler ultrasound (DUS) at rest was insufficient to assess the severity of peripheral artery disease (PAD). Toe pressure and transcutaneous tissue oxygen pressure were studied to prove whether these could identify more patients with severe lower limb ischemia; exercise was applied to provoke ischemia. METHODS: 120 patients with PAD and 30 volunteers without PAD were recruited. DUS, transcutaneous tissue oxygen pressure (tcpO2) and toe pressure measurements were performed at rest and after exercise. The differential power of these examinations for severe limb ischemia (SLI) was determined by receiver-operating curves (ROCs) and pattern recognition by independent multicategory analysis (PRIMA). RESULTS: There was an obvious significant difference between the patient and control groups at rest; after exercise; the ratio of severely impaired values (ankle-brachial index - ABI, toe-brachial index - TBI, tcpO2 measured on index forefoot) increased significantly in the patient group (p < 0.05). TBI, tcpO2, ABI measured after exercise could differentiate SLI better than the values of these tests at rest (p < 0.001). In ROC analysis, the largest area under the curve (AUC) was covered by post- (AUC: 0.860) and pre-exercise TBI (AUC: 0.785), and post-exercise tcpO2 (AUC: 0.720) (p < 0.001). Post-exercise TBI gained the best discriminant score in PRIMA. CONCLUSIONS: Pre- and post-exercise non-invasive vascular tests could reveal severe limb ischemia. Toe pressure measurement and TBI should become a basic part of the vascular workup.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications.

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

[Clopidogrel resistance in cerebrovascular disease -- results of one-year follow-up]. / Clopidogrelrezisztencia vizsgálata cerebrovascularis betegségben -- egyéves utánkövetés.

INTRODUCTION: In an earlier study the authors reported short-term benefits of clopidogrel treatment in patients with cerebrovascular disease. AIM: The aim of the authors was to analyze findings during a 12-month follow-up period. METHOD: 100 patients with a history of acute stroke or transient ischaemic attack have been included in the study. The efficacy of the therapy was assessed 7 and 28 days as well as 3, 6 and 12 months after initiation of medical therapy. Patients were divided into two parts (clopidogrel responder and resistant) based on their initial laboratory findings. Risk profiles, medical therapy, laboratory parameters and vascular events were compared between the two patient groups. RESULTS: After 7 days of treatment, clopidogrel seemed to be ineffective in 11 patients (11%). Strong, clinically significant correlations were found among blood pressure values, blood glucose and lipid parameters, serum C-reactive protein levels and platelet aggregation levels. An aggressive secondary preventive therapy resulted in a decrease of clopidogrel resistance and improvement in laboratory parameters. Patients who were clopidogrel resistant at baseline had significantly higher rate of vascular events compared to those who were clopidogrel responders (18.1 vs. 4.5%, p<0.01), although clopidogrel resistance was not an independent risk factor of unfavourable vascular outcome using a multivariate analysis. No adverse events or hemorrhagic complications were observed. CONCLUSIONS: Clopidogrel resistance and unfavourable outcome seems to be associated with "classical" risk factors underlying the importance of aggressive secondary prevention.

Gender differences in hemorheological parameters and in in vitro platelet aggregation in acetylsalicylic acid and clopidogrel treated vascular patients.

BACKGROUND: Sex-specific response to antiplatelet medications have been reported in several previous studies. OBJECTIVE: We investigated a possible connection between gender differences in hemorheological parameters and in vitro platelet aggregation in vascular patients treated with widely used antiplatelet agents. METHODS: In vitro platelet aggregation was assessed in 2687 patients treated with 100 mg acetylsalicylic acid (ASA), 1047 patients treated with 75 mg clopidogrel and 311 patients on dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) according to the method of Born. In subgroups of patients fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and hematocrit were simultaneously measured. The subjects were divided into groups according to their gender. RESULTS: ADP induced platelet aggregation was significantly higher in women in the case of ASA treatment (p<0.001). No gender differences could be observed in platelet function in patients treated with clopidogrel or on dual antiplatelet therapy. Hematocrit and whole blood viscosity were significantly higher in men in all groups (p<0.001), while no significant gender differences were observed in red blood cell aggregation indices in either group. Fibrinogen concentration was significantly higher in women than in men among patients treated with 100 mg ASA (p<0.05), but not in the other groups. CONCLUSIONS: Significantly higher fibrinogen concentration found in aspirin treated women than men may play a role in higher ADP induced platelet aggregation. Gender differences in response to monotherapy suggest that benefits from combination therapy may be greater in females. The clinical relevance of higher ADP induced platelet aggregation in women treated with ASA needs further investigation.

Statintherapy in the primary and the secondary prevention of ischaemic cerebrovascular diseases.

INTRODUCTION: Stroke is a major public health problem. It is the third leading cause of death worldwide and results in hospital admissions, morbidity, and long-term disability. Despite the inconsistent or weak association between cholesterol and stroke, statins can reduce the incidence of stroke in high-risk populations and in patients with a stroke or transient ischaemic attack. METHODS: The aim of our study was to review the efficacy of statin therapy in both primary and secondary stroke prevention. We also reviewed the effectiveness and cost-effectiveness among different statins and we also reviewed the possible effect of treatment added to statin monotherapy. RESULTS: There is evidence that statin therapy in both primary and secondary prevention significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence. There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later. There is a pressing need for direct evidence, from head-to-head trials, to determine whether individual statins provide differing protection from clinically important events in stroke prevention. It is possible that combinations of lipid-lowering agents did not improve clinical outcomes more than high-dose statin monotherapy, although clinical trials are still ongoing.

Clinical importance of aspirin and clopidogrel resistance.

Aspirin and clopidogrel are important components of medical therapy for patients with acute coronary syndromes, for those who received coronary artery stents and in the secondary prevention of ischaemic stroke. Despite their use, a significant number of patients experience recurrent adverse ischaemic events. Interindividual variability of platelet aggregation in response to these antiplatelet agents may be an explanation for some of these recurrent events, and small trials have linked "aspirin and/or clopidogrel resistance", as measured by platelet function tests, to adverse events. We systematically reviewed all available evidence on the prevalence of aspirin/clopidogrel resistance, their possible risk factors and their association with clinical outcomes. We also identified articles showing possible treatments. After analyzing the data on different laboratory methods, we found that aspirin/clopidogrel resistance seems to be associated with poor clinical outcomes and there is currently no standardized or widely accepted definition of clopidogrel resistance. Therefore, we conclude that specific treatment recommendations are not established for patients who exhibit high platelet reactivity during aspirin/clopidogrel therapy or who have poor platelet inhibition by clopidogrel.

Enhancement of organ regeneration in animal models by a stem cell-stimulating plant mixture.

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

Association between XRCC1 polymorphisms and head and neck cancer in a Hungarian population.

BACKGROUND: Head and neck cancer is a significant current health problem in Hungary because the mortality of this cancer has increased by 387% in the last thirty-two years. Because of the important role of the XRCC1 gene in DNA repair, we wanted to test the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 on the clinical outcome of head and neck cancer. PATIENTS AND METHODS: A polymerase chain reaction-restriction fragment lenght polmorphism (PCR-RFLP) method was used. A total of 108 samples were taken from intraoperatively removed formalin-fixed, and paraffin-embedded blocks of tissue. An age- and sex-matched cancer-free control group was used to compare the frequency of polymorph variants. RESULTS: No significant difference was found between patients and controls in repect of the investigated polymorphisms. A significant difference was found between the patients with different XRCC1 194 polymorph status in clinical stage SIII. The survival proportion of patients with the Arg194Arg genotype was significantly lower than of those with the Arg194Trp genotype. CONCLUSION: The complex analysis of these factors may provide the basis for personal risk assessment and an opportunity for individualised therapy.

Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases.

INTRODUCTION: Hemorheological factors play an important role in the pathomechanism of ischemic cerebrovascular disorders. Abnormal rheological conditions in patients with chronic cerebrovascular disease predispose for recurrent strokes. Vinpocetine (VP), a synthetic ethyl esther of apovincamine, has successfully been used in the treatment of cerebrovascular diseases, in part because of its favourable rheological effects. PATIENTS AND METHODS: The study investigates the hemorheological changes in 40 patients in the chronic stage of ischemic cardiovascular disease after administration of vinpocetine. All patients received a high dose of intravenous VP in doses gradually increased to l mg/kg/day. In addition, 20 patients (mean age: 61+/-8 years) received 30 mg VP orally for 3 months. The other 20 patients (mean age: 59+/-6 years), who received placebo tablets, served as controls. Hemorheological parameters (hematocrit, plasma fibrinogen, whole blood viscosity, red blood cell aggregation and deformability) were evaluated at 1 and 3 months. RESULTS: The high-dose parenteral VP significantly decreased red blood cell aggregation, plasma and whole blood viscosity (p < 0.05) compared to the initial values. In patients with additional oral treatment, plasma and whole blood viscosities were significantly lower compared to the placebo patients at 3 months (p < 0.05). CONCLUSION: Our results confirmed the beneficial rheological effects of high-dose parenteral VP (partially caused by hemodilution) observed previously, and also warrant its long-term oral admission to maintain the beneficial rheological changes.