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.

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.

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.

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.

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.

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.

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.

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.

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.

GSTM, GSTT and p53 polymorphisms as modifiers of clinical outcome in colorectal cancer.

BACKGROUND: Cancer of the colorectal region is the second most frequent cause of death among malignant diseases. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. PATIENTS AND METHODS: Intraoperatively removed tissue samples were processed from colorectal cancer patients. Cancer-free human samples were used as matched controls. Samples were digested with proteinase-K. DNA solution was used for PCR amplification. RESULTS: No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant association was found in Dukes' B stage patients between the GSTM1 and p53 gene variants and survival. In patients with GSTM1 null genotype and p53 Arg/Pro heterozygotes or Pro/Pro homozygotes the chance of survival is significantly lower than in the case of GSTM1+ and p53 Arg/Arg variants (p=0.009 and p=0.008, respectively). CONCLUSION: The significance of the investigated polymorphisms in prognosis is dependent on the tumor stage. These parameters might be used in certain cases as prognostic biomarkers in clinical diagnostics and in the planning of individual therapy.

Hemorheological background of acetylsalicylic acid resistance.

BACKGROUND: Pathologic hemorheological parameters and increased platelet aggregation in association with other risk factors significantly increase the possibility of the development of ischemia. Acetylsalicylic acid (ASA) is an effective antithrombotic agent, which prevents a variety of cardiovascular diseases. OBJECTIVES: The aim of our present study was to compare the hemorheological parameters of patients with effective platelet inhibition by ASA to those with ineffective one. METHODS: 2045 patients taking 100 mg ASA daily were involved in our study (1255 males, mean age: 63+/-11 yrs, 790 females, mean age: 63+/-12 yrs). To exclude the effect of risk profile, previous diseases and medication, 323 patients (197 males, mean age 60+/-13 yrs and 126 females, mean age 60+/-12 yrs) were selected from the examined group with matching parameters. Blood was taken after an overnight fast between 8:00 and 9:00 a.m. Platelet aggregation was measured in Carat TX-4 optical platelet aggregometer. Blood hematocrit was measured by Heraeus microhematocrit centrifuge and red blood cell aggregation was detected by Myrenne aggregometer. Plasma fibrinogen was measured by Clauss' method. Plasma and whole blood viscosities were measured in Hevimet 40 capillary viscosimeter. RESULTS: Patients with effective ASA inhibition had significantly lower plasma fibrinogen level (p<0.05) and red blood cell aggregation values both in the heterogenous and the selected populations (p<0.01). The other hemorheological parameters were not statistically different in the two groups. CONCLUSION: The background of ineffective ASA medication has not yet been fully elucidated. Higher fibrinogen concentration increases red blood cell aggregation and can also result in increased platelet aggregation. Thus, increased plasma fibrinogen level may play an important role in the in vitro and in vivo platelet resistance to ASA.

Relation of platelet aggregation and fibrinogen levels to advancing age in aspirin- and thienopyridine-treated patients.

In our present study we investigated the association between platelet aggregation in patients treated with the most widely used antiplatelet agents (100 and 300-325 mg acetylsalicylic acid (ASA), 75 mg clopidogrel, 500 mg ticlopidine and the combination of 100 mg aspirin and 75 mg clopidogrel), fibrinogen levels and aging. Between 2001 and 2005 we measured in vitro platelet aggregation in 5026 vascular patients according to the method of Born. Platelet aggregation was tested with 5 and 10 microM adenosine-diphosphate, 2 microg/ml collagen and 10 microM epinephrine stimulants. Fibrinogen level was simultaneously measured in a subgroup of 3243 patients. The subjects were divided by age into decades. Platelet aggregation increased significantly with advancing age in the case of 100 and 300-325 mg ASA-treated patients (p<0.001). In aspirin-treated patients also fibrinogen levels increased with aging (p<0.001). There was no association between platelet aggregation or fibrinogen levels and aging either in patients treated with 75 mg clopidogrel or with 500 mg ticlopidine. Thienopyridine-treated patients exhibited significantly lower fibrinogen levels than ASA-treated individuals (p<0.001). Our results suggest that advancing age is associated with elevated platelet aggregability in widely used antiplatelet regimens that might contribute to higher risk of cardiovascular events in the elderly.

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.

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.

[The effect of carotid stenting on rheological parameters, free radical production and platelet aggregation]. / Carotisstent-beültetés hatása a rheologiai paraméterekre, a szabadgyök-képzodésre és a thrombocytaaggregációra.

INTRODUCTION: Carotid artery stenting has become a possible treatment of significant carotid stenosis. The risk of stent occlusion and restenosis might be increased by abnormal rheological conditions amplified platelet aggregation and free radical production during the operation. AIMS: The aim of this study was to assess the changes of the rheologic parameters, platelet aggregation, and oxidative stress after endovascular treatment of carotid stenosis. METHODS: 18 patients (11 men, ages 68 +/- 9 years and 7 women, ages 62 +/- 8 years) suffering from significant carotid stenosis and treated with carotid endovascular intervention were examined. Alteration in hemorrheological parameters as well as epinephrine-, ADP-, and collagen-induced platelet aggregation were evaluated. Oxidative stress was characterized by the determination of catalase activity. The measurements were carried out directly before and after the procedure and 1, 2, 5 days and 1 month following the intervention. Preceding the operation the patients were administered a maximum dose (300 mg) of clopidogrel. RESULTS: The hematocrit, the plasma fibrinogen concentration (Pfc) and whole blood-, and plasma viscosity (Wbv and Pv) decreased significantly immediately after stenting ( p < 0.001). By the fifth day following the intervention the Pfc, Wdv, Pv, red blood cell (Rbc) aggregation and ADP-induced platelet aggregation increased significantly ( p < 0.0001) compared to values measured after the procedure. At 1 month follow-up these parameters, excepting Wbv, decreased significantly compared to measurements made on the 5th day. On the other hand, catalase activity showed significant elevation by the end of the first month. CONCLUSION: Hemorrheological parameters and platelet aggregation showed specific changes following carotid stenting. Abnormal changes of the rheological conditions and increasing platelet activation are the most pronounced in the first week following stenting, which may lead to the stent's early occlusion. Oxidative stress production returned to baseline levels only by the end of the first month.

Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables.

BACKGROUND AND OBJECTIVE: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. METHODS: 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. RESULTS: Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). CONCLUSIONS: The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.

The effect of blood glucose levels on hemorheological parameters, platelet activation and aggregation in oral glucose tolerance tests.

Rheological factors and increased platelet aggregation are convincingly implicated in the development of micro- and macrovascular disease associated with diabetes mellitus. The present examination has been designed to describe the effects of a standard oral glucose load on hemorheological parameters, platelet activation and aggregation in patients with normal and pathologic glucose tolerance. Oral glucose tolerance test (OGTT) was performed in 30 patients suspected to have diabetes mellitus. Hematocrit, erythrocyte aggregation, red blood cell filterability, plasma and whole blood viscosity, soluble P-selectin levels and platelet aggregation were tested paralelly with blood glucose measurements 1, 2, and 3 hours after glucose consumption. Patients were divided into two groups based on glucose tolerance. Patients with abnormal glucose tolerance (IGT/DM) showed significant elevation in red blood cell aggregability (Myrenne indices M and M1) at the 2- and 3-hour samplings (p<0.01 and p<0.001, respectively). Patients with normal glucose tolerance (NGT) showed significant elevation only in M1 index (p=0.01). Plasma viscosity decreased significantly compared to fasting values in IGT/DM patients in all samples, but remained unchanged in NGT patients. Hematocrit decreased in IGT/DM patients significantly from the 2-hour samplings on (p<0.05), in normoglycaemic patients its decrease reached a borderline significance at 3-hour measurements. No significant changes were detected in whole blood viscosity, red blood cell filterability and sP-selectin levels during OGTT in either examined groups. No examined parameters were significantly correlated to blood glucose levels at any sampling. Erythrocyte aggregation showed significant correlation with BMI (p<0.01). Our results demonstrate that after the intake of a standard amount of glucose the development of rheological alterations is not simultaneous with the elevation of blood glucose levels, and our data suggest that the observed elevation in erythrocyte aggregation during OGTT might be associated with hyperinsulinemia.

Viscosity, hemostasis and inflammation in atherosclerotic heart diseases.

BACKGROUND: In atherosclerotic diseases vascular reserve is impaired and pressure gradient is decreased, therefore the reduced blood fluidity can lead to tissue ischemia more rapidly. In previous investigations we demonstrated the deterioration of plasma and whole blood viscosities in patients with acute ischemic coronary syndromes, chronic coronary artery disease, and percutaneous transluminal coronary angioplasty. METHODS: Hemorheological variables (plasma and whole blood viscosities, hematocrit, red blood cell aggregation), hemostaseological parameters (plasma fibrinogen and von Willebrand factor (vWf)), and platelet aggregation were detected in more recent studies in cardio- and cerebrovascular diseases, and diabetes mellitus. Common risk factors (lipid profile, smoking, glucose level, previous diseases) and medication were also recorded. RESULTS: High portion of vascular patients were demonstrated to have poor ex vivo platelet inhibition. Effective antiplatelet treatment detected by aggregometry was related to lower plasma fibrinogen concentration and red blood cell aggregation and was also associated with less recurrent vascular events during the follow-up (p < 0.001). Beside the impaired hemorheological characteristics, the diabetic patients showed elevated vWf activity, which turned to correlate with hemoglobin A1c concentration (p < 0.01) rather than the fasting glucose. SUMMARY: Our studies indicate the active role and interaction of hemorheological and hemostaseological factors in atherosclerotic heart diseases.