Biomedical subjects

Cezary Watala

Publications and source records attributed to Cezary Watala.

At least 19 recordsLinked to original sources

PubMed2006

A comparative assessment of HER2 status in operable breast cancer by real-time RT-PCR and by immunohistochemistry.

BACKGROUND: The most commonly used methods for detecting HER2 gene amplification in breast cancer are immunohistochemistry and fluorescence in-situ hybridization. The aim of this retrospective study was to assess HER2 expression by real-time RT-PCR. MATERIAL/METHODS: Expression of HER2 was analyzed by real-time RT-PCR and immunohistochemistry in specimens of invasive ductal breast cancer tissue obtained from 131 women during radical mastectomy. RESULTS: There was a highly significant difference in mean relative gene expression between HER2-positive and HER2-negative patients as assessed by immunostaining (22.10+/-41.89 vs. 3.17+/-8.76; p<0.001). With a median follow-up of 56 months, the cancer-specific survival of HER2-positive patients assessed by RT-PCR was worse in all cases and in the node-positive group. In multivariate analysis, HER2 status was an independent prognostic factor in all patients. CONCLUSIONS: Real-time RT-PCR is a valuable method for determining HER2 status, but the selection of the cut-off point of the relative gene expression differentiating between HER2-negative and -positive tumors is essential.

Adult↗

PubMed2006

Ki-67 expression in operable breast cancer: a comparative study of immunostaining and a real-time RT-PCR assay.

The main purpose of this retrospective study was to compare Ki-67 expression in operable breast cancer examined by immunostaining and real-time reverse transcriptase polymerase chain reaction (RT-PCR). Relations between Ki-67 and classic prognostic factors were also investigated, and the prognostic relevance of Ki-67 expression was examined. Expression of Ki-67 was analyzed in specimens of invasive ductal breast cancer tissue obtained from 131 women during radical mastectomy. There was a significant, but weakly positive, correlation between Ki-67 expression assessed by immunostaining and real-time RT-PCR (tau=0.154, p=0.005). Higher Ki-67 expression in immunostaining and RT-PCR was more often seen in grade 3 tumors (p<0.001 and p=0.026, respectively). No significant relationship with age, disease stage, nodal involvement, estrogen receptor or HER2 status was found. In a univariate and multivariate analysis of cancer-specific survival with a median follow-up of 56 months, Ki-67 expression determined by immunostaining or real-time RT-PCR was no prognostic factor. We demonstrated that Ki-67 expression levels measured by immunostaining and real-time RT-PCR were weakly concordant, and both were related to higher tumor grade. Ki-67 expression did not influence survival.

Adenocarcinoma↗

PubMed2006

Cyclin E expression in operable breast cancer quantified using real-time RT-PCR: a comparative study with immunostaining.

OBJECTIVE: The main purpose of this retrospective study was to compare cyclin E expression levels in operable breast cancer patients determined using real-time RT-PCR and immunostaining. The prognostic relevance of cyclin E was also investigated. METHODS: Specimens of invasive ductal breast cancer tissues obtained from 124 women during radical mastectomy were analyzed. RESULTS: Of the tumor samples, 40.3 and 59.7% showed high expression of cyclin E in RT-PCR and immunostaining, respectively. The overall agreement probability was 0.032 according to Scott's pi statistic. With a median follow-up of 55.5 months, cyclin E expression assessed using immunostaining was an independent negative prognostic factor in the node positive group (hazard ratio 3.1; 95% CI 1.0-9.2; P = 0.045). Cyclin E expression correlated with absence of steroid receptors and younger age. RT-PCR results did not predict survival in any group of patients. CONCLUSIONS: Disagreement between real-time RT-PCR and immunostaining was demonstrated. Immunostaining seems to be the more reliable method for assessing cyclin E in breast cancer cells.

Adult↗

PubMed2006

Acetylsalicylic acid is compounding to antiplatelet effect of C-reactive protein.

The contribution of inflammatory process to the modulation of platelet response to acetylsalicylic acid (ASA) remains obscure. In our study, we examined the in vitro effect of C-reactive protein (CRP) on the ASA-mediated inhibition of collagen-stimulated platelet reactivity. Influence of CRP on platelet responsiveness to ASA was analysed using classical turbidimetric aggregation and flow cytometry. When acting alone, both C-reactive protein and ASA inhibited collagen-dependent platelet aggregation and reduced the expressions of two platelet surface membrane activation markers: P-selectin and activated GPIIbIIIa complex. Compared to the effects observed for ASA alone, the simultaneous action of both agents lead to further reductions in platelet aggregation (by 56.7+/-1.0% vs. 14.9+/-0.6%, p<0.0001) and lowered the expressions of platelet surface membrane P-selectin (by 72.1+/-5.3% vs. 65.0+/-6.0%, p<0.01) and activated GPIIbIIIa (by 67.0+/-5.6% vs. 47.7+/-8.3%, p<0.01). In general, our findings showed for the first time the augmenting effect of native C-reactive protein in the antiplatelet action of acetylsalicylic acid. Thus, we conclude that the effectiveness of aspirin therapy may strongly depend upon the presence of native CRP in circulation.

Adult↗

PubMed2006

Prognostic relevance of basal cytokeratin expression in operable breast cancer.

OBJECTIVE: We investigated whether basal cytokeratin (CK5/6 or CK17) expression had an impact on survival in patients with operable breast cancer. METHODS: Expression of CK5/6 or CK17 was analyzed by immunohistochemistry in 195 women with breast cancer. RESULTS: In total, 72 (37%) tumor samples were regarded as being positive for CK5/6 or CK17. The basal-like phenotype as defined by basal cytokeratin expression, lack of estrogen receptor (ER) and absence of HER2 overexpression was found in 48 (25%) cases. Positive staining for CK5/6 or CK17 was associated with worse prognosis when compared with patients negative for basal cytokeratins in all cases (5-year cancer-specific survival rate 59.4 vs. 77.5%, p = 0.0273) and in the node-negative group (70.5 vs. 90.8%, p = 0.0208) but not in the node-positive group (43.9 vs. 65.4%, p = 0.1182). To determine the real prognostic value of basal cytokeratins, survival in a group of ER-negative patients was analyzed depending on CK5/6 or CK 17 expression. No influence on survival was observed. The outcome of patients whose cancers were positive for cyclin E regardless of ER status was not changed by CK5/6 or CK17 expression. In multivariate analysis, independent prognostic factors affecting survival in the whole group included: nodal involvement, HER2 status and cyclin E expression. Neither ER status nor basal cytokeratin expression retained statistical significance. CONCLUSION: We demonstrated that the poor prognosis associated with the basal-like phenotype of breast cancer was determined by ER absence and cyclin E expression and not by CK5/6 or CK17 expression.

Adult↗

PubMed2006

High glucose contributes to aspirin insensitivity in streptozotocin-diabetic rats: a multiparametric aggregation study.

The effect of chronic hyperglycaemia on blood platelet response to acetylsalicylic acid was studied in rats with experimental diabetes. Platelet aggregation was determined in non-diabetic and streptozotocin-diabetic rats treated orally with 4 or 40 mg aspirin (ASA)/kg per day (for 8 weeks from the eighth day of diabetes) using whole blood impedance aggregometry with arachidonic acid or ADP as platelet agonists. The dose-dependent effect of ASA 'therapy' on ADP-agonized platelets was significant only in non-diabetic animals, while in diabetic rats both doses were ineffective in reducing ADP-stimulated platelet aggregation. ASA-mediated increased acetylation of platelet proteins favoured reduced platelet aggregation and slower platelet disaggregation (Pr < 0.025 or less). Interestingly, however, the occupation of platelet protein-free amino groups was significantly higher in control rats compared with diabetic rats (P < 0.001), pointing out that proteins of platelets in non-diabetic animals were more vulnerable for the ASA-induced acetylation. We conclude that chronic hyperglycaemia interferes with preventive effects of ASA on platelet reactivity. Our data validate the suggestion that the relationship between aspirin ineffectiveness and poor metabolic control, first revealed in humans, concerns also other animals' platelets and holds regardless of the model or type of diabetes.

Animals↗

PubMed2006

Reduced blood platelet sensitivity to aspirin in coronary artery disease: are dyslipidaemia and inflammatory states possible factors predisposing to sub-optimal platelet response to aspirin?

The study was designed to assess blood platelet sensitivity to acetylsalicylic acid and its associations with dyslipidaemia and inflammation in coronary artery disease patients. Platelet non-responsiveness to aspirin is associated with an increased risk of serious cardiovascular events. Several environmental and hereditary factors are reportedly involved in sub-optimal acetylsalicylic acid response. Forty-five coronary artery disease patients and 45 non-coronary artery disease controls received acetylsalicylic acid at a daily dose of 75-150 mg. Controls were examined twice: on the day of entering the study and 10 days later. Urinary 11-dehydrothromboxane B2 was assessed as the marker of platelet thromboxane generation. Aggregation was studied in platelet-rich plasma using turbidimetric aggregometry with collagen and arachidonic acid. Fifty to seventy percent of coronary artery disease patients showed an extent of collagen-induced aggregation above the upper quartile of the reference range compared with 8-15% in controls (P<0.003). For arachidonic acid-activated aggregation these proportions were 45-50% in coronary artery disease versus 7% in controls (P<0.007). In coronary artery disease patients, the acetylsalicylic acid-mediated platelet inhibition positively correlated with increased triglycerides (in arachidonic acid-stimulated platelets, r=0.30, P=0.0018), total cholesterol (r=0.33, P<0.0001 in coll and arachidonic acid-activated platelets) and elevated serum C-reactive protein (CRP) (r=0.27, P=0.0024). In coronary artery disease patients urine 11-dehydrothromboxane B2 concentrations were significantly increased compared to controls after 10 day acetylsalicylic acid intake (563; 313-728 pg/mg creatinine versus 321; 246-488 pg/mg creatinine, P=0.04). The incidence of suboptimal acetylsalicylic acid response incidence was more common in patients with coronary artery disease. Acetylsalicylic acid inhibition of blood platelet reactivity and thromboxane generation was less effective in these patients. Dyslipidaemia and chronic inflammatory states may promote suboptimal acetylsalicylic acid response in coronary artery disease patients.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2006

Usefulness of whole blood aggregometry and its comparison with thromboxane generation assay in monitoring acetylsalicylic acid effectiveness--a multiparametric study in rats.

BACKGROUND: There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A(2) generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness. METHODS: Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40 mg/kg for 60 days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B(2) and urine 11-dehydro-thromboxane B(2), accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition. RESULTS: Two of the platelet agonists used, collagen (1 mg/L) and arachidonic acid (0.5 mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5 micromol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B(2). CONCLUSIONS: Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules.

Adenosine Diphosphate↗

PubMed2006

[Role of C-reactive protein in atherogenesis].

C-reactive protein (CRP), formerly considered solely an excellent biomarker of inflammation, is now viewed as a direct contributor in atherosclerosis. With the advent of high-sensitivity assays for determining CRP, this protein has emerged as one of the most powerful independent predictors of cardiovascular disease. CRP level, which significantly increases in acute coronary syndromes, has a prognostic value in cardiovascular risk not only in patients with cardiovascular complications, but also in apparently healthy individuals. The in vivo mechanisms of CRP as a mediator of the inflammatory state and thrombotic complications are continuing to be unraveled. Here we focused on the role of C-reactive protein in the pathophysiology of atherosclerosis, including the potential mechanisms of CRP's action in the circulation, as well as the potential contribution of genetic variations within the CRP gene in the pathophysiology of vascular complications.

Biomarkers↗

PubMed2005

Increased blood plasma hydrolysis of acetylsalicylic acid in type 2 diabetic patients: a role of plasma esterases.

Hydrolysis of acetylsalicylic acid (ASA, aspirin), an antiplatelet drug commonly used in the prevention of stroke and myocardial infarction, seems to play a crucial role in its pharmacological action. Thirty-eight healthy volunteers and 38 type 2 diabetic patients were enrolled to test the hypothesis that the enhanced plasma degradation and lowered bioavailability of ASA in diabetic patients is associated with the attenuation of platelet response. Aspirin esterase activities were tested at pH 7.4 and 5.5. A significantly higher overall aspirin esterase activity was noted at pH 7.4 in the diabetic patients (P<0.003), corresponding to faster ASA hydrolysis (P<0.006). This increased activity was attributable to butyrylcholinesterase and probably to albumin, because it was effectively inhibited by eserine and 4-bis-nitrophenyl phosphate (P<0.01). No significant differences between control and diabetic subjects were found at pH 5.5 in either enzymatic activities or ASA hydrolysis rates. The enhanced plasma ASA degradation in diabetic subjects was significantly associated with the refractoriness of blood platelets to ASA (P<0.05) and modulated by plasma cholesterol (P<0.01). No direct effects of plasma pH or albumin were observed. In conclusion, higher aspirin esterase activity contributes to the lowered response of diabetic platelets to ASA-mediated antiplatelet therapy.

Adult↗

PubMed2005

Adenosine diphosphate receptors on blood platelets: potential new targets for antiplatelet therapy.

Platelets play a key role not only in physiological haemostasis, but also under pathological conditions such as thrombosis. Platelet activation may be initiated by a variety of agonists including thrombin, collagen, thromboxane or adenosine diphosphate (ADP). Although ADP is regarded as a weak agonist of blood platelets, it remains an important mediator of platelet activation evoked by other agonists, which induce massive ADP release from dense granules, where it occurs in molar concentrations. Thus, ADP action underlies a positive feedback that facilitates further platelet aggregation and leads to platelet plug formation. Additionally, ADP acts synergistically to other, even weak, agonists such as serotonin, adrenaline or chemokines. Blood platelets express two types of P2Y ADP receptors: P2Y(1) and P2Y(12). ADP-dependent platelet aggregation is initiated by the P2Y1 receptor, whereas P2Y(12) receptor augments the activating signal and promotes platelet release reaction. Stimulation of P2Y(12) is also essential for ADP-mediated complete activation of GPIIb-IIIa and GPIa-IIa, and further stabilization of platelet aggregates. The crucial role in blood platelet biology makes P2(Y12) an ideal candidate for pharmacological approaches for anti-platelet therapy.

Animals↗

PubMed2005

Resistance to aspirin in patients after coronary artery bypass grafting is transient: impact on the monitoring of aspirin antiplatelet therapy.

The aim of the present study was to assess the responsiveness of blood platelets to aspirin in patients following coronary artery bypass grafting (CABG) surgery. Aspirin was administered following CABG in 24 operated patients (aged 63.2 +/- 6.3 years). Platelet function was monitored on the 10th postoperative day (A) and 1 month after CABG (B) with the use of whole-blood aggregometry (WBEA) and PFA-100 closure time (PFA-100 CTCEPI). Normal platelet response to aspirin was defined by 3 criteria: the complete inhibition of WBEA induced by arachidonic acid (0.5 mmol/L), partial inhibition of collagen (1 microg/mL)-induced aggregation (WBEA < 14 Omega), and prolongation of PFA-100 CTCEPI (>150 seconds) ("good responders"). Depending on whether 0, 1, 2, or 3 of these 3 criteria were fulfilled, patients were classified as "nonresponders," "weak responders," "incomplete responders," or "good responders," respectively. On the 10th postoperative day, there were 3 good responders, 6 incomplete responders, 11 weak responders, and 4 nonresponders among 24 patients. In contrast, 1 month after CABG within the same group of 24 patients there were 18 good responders, 5 incomplete responders, and 1 weak responder. Using a new methodology to assess impaired platelet responsiveness to aspirin ex vivo, we describe here the transient nature of "aspirin resistance" following CABG. These results indicate the necessity for the prolonged monitoring of the antiplatelet effectiveness of aspirin in the postoperative period after CABG.

Aged↗

PubMed2005

Blood platelet reactivity and its pharmacological modulation in (people with) diabetes mellitus.

Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.

Animals↗

PubMed2005

Blood platelet abnormalities and pharmacological modulation of platelet reactivity in patients with diabetes mellitus.

The overall picture of platelet abnormalities in diabetes mellitus (DM), including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilization often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. The paper concentrates on the role of dynamic, physico-chemical properties of platelet membrane lipid bilayer, as a major determinant of platelet hypersensitivity in diabetic patients. As a pharmacological response to platelet hypersensitivity in DM, making a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality in diabetic individuals, we have a variety of antiplatelet agents, and acetylsalicylic acid (ASA) is no doubt most commonly used worldwide. Everyday clinical practice shows that antiplatelet pharmacological approach may not always be efficient enough in people with diabetes. Although we are at the very beginning of complete understanding of so-called 'aspirin-resistance', several potential molecular mechanisms of this phenomenon in diabetes have been evidenced.

Aspirin↗

PubMed2004

Increased protein glycation in diabetes mellitus is associated with decreased aspirin-mediated protein acetylation and reduced sensitivity of blood platelets to aspirin.

Reduced effectiveness of the most common antiplatelet drug, acetylsalicylic acid (ASA, aspirin), in diabetes mellitus has been associated with a lowered platelet sensitivity to ASA and related to glycemic control in diabetic patients. Our objectives were (a) to monitor the chemical background of how chronic hyperglycemia affects platelet response to ASA in diabetes and (b) to study a chemical competition between the amount of bound acetyl residues and the extent of protein glycation in blood platelets. Using whole-blood impedance aggregometry and platelet function analyzer (PFA-100) we observed a reduced platelet response to ASA in diabetic patients (14% vs. 79% for PFA-100 collagen-epinephrine occlusion time) and an association between the index of glycemic control and platelet refractoriness to ASA (r(S) = -0.378). Impaired platelet response to ASA was related to enhanced platelet protein glycation (3.6+/-0.4 in diabetes vs. 2.3+/-0.4 micromol fructosamine/microg protein in control) and reduced incorporation of acetyl residue into proteins of platelets from diabetic patients (47.4+/-2.0 in control vs. 33.1+/-0.7 micromol acetyl/microg protein in diabetic subjects). Incubation of blood platelets with increasing concentrations of glucose and ASA under in vitro conditions led to excessive modification in protein amino groups: glucose and ASA competed with each other in the course of nonenzymatic modifications, glycosylation, or acetylation, and their contributions to the occupancy of protein amino groups (R2 = 0.22 for glucose, R2 = 0.43 for ASA) were dependent upon the concentrations of glucose and ASA. Overall the effects of high glucose and high ASA on the overall occupancy of protein free amino groups are not additive. While at higher concentrations ASA overcomes the effects of hyperglycemia and retards glycation, high glucose makes acetylation less efficient, and therefore the resultant chemical modification becomes greatly reduced. In conclusion, diminished susceptibility of various platelet proteins and receptors on blood platelet membranes to acetylation and high ambient glucose might underlie the apparently differentiated sensitivity of blood platelets to ASA and determine platelet "insensitivity to aspirin" in diabetic patients.

Acetylation↗

PubMed2004

Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control.

Aspirin (acetylsalicylic acid, ASA), which is recommended for primary and secondary prevention in diabetes mellitus (DM), has been shown to have a lower antiplatelet activity in diabetic patients. We conducted a crossover designed observational study to evaluate whether there is an association between the parameters relevant to metabolic control of diabetes and platelet sensitivity to aspirin in type 2 diabetic patients. Platelets' ability to adhere and aggregate was monitored with the use of platelet function analyser (PFA-100 collagen/epinephrine closure time, CT(CEPI) or collagen/ADP closure time, CT(CADP)), classical turbidimetric aggregometry and whole blood electrical aggregometry (WBEA), using collagen (WBEA(coll)), ADP (WBEA(ADP)) and arachidonic acid (WBEA(AA)) as platelet agonists, in 48 control healthy volunteers (mean age+/-S.D., 49+/-9 years) and 31 type 2 DM patients (50+/-9 years; HbA(1c) 9.4+/-1.6%). In majority of control subjects (69%) and minority of diabetic patients (29%, p=0.0006), the use of 150 mg aspirin daily for 1 week significantly reduced platelet adhesiveness and reactivity (by 14.1% in diabetes vs. 78.6% in control, p(np)=0.0035, as expressed by the relative changes in CT(CEPI)). Aspirin reduced WBEA(coll) and WBEA(AA) to a lesser extent in diabetic patients (by 2.1% vs. 8.3% in controls, p(np)=0.0397, and by 97.3+/-12.8% vs. 100% in controls, p(np)=0.0383, respectively), which corresponded to ASA-mediated decreased aggregation in platelet-rich plasma (PRP, r(S)=0.45 and r(S)=0.78 for collagen- or arachidonate-agonized platelets, p<0.01 or lower). The maximal inhibition of platelet aggregation was lower and IC(50) higher in diabetic compared to control subjects, both in the presence of arachidonic acid (71% vs. 39%, p(np)0.0001; 0.5 microg/ml vs. 1.3 microg/ml, p<0.0001) and collagen (52% vs. 35%, p<0.0004; 1.6 microg/ml vs. 2.1 microg/ml, p<0.01). The reduced response of platelets from diabetic subjects to aspirin was associated with a higher level of HbA(1c), lower concentration of HDL-cholesterol and a higher total cholesterol concentration. Overall, there is evidence that reduced platelets response to aspirin may occur more often in diabetic patients. Poor metabolic control may play a role in the reduced platelet sensitivity to aspirin in DM patients. Thus, our findings strongly support the requirements for an excellent near-normal metabolic control and may suggest a need for alternative ASA dosing schedules in DM patients.

Adult↗

PubMed2004

Common carotid artery remodeling studied by sonomorphological criteria.

BACKGROUND AND PURPOSE: Only a few attempts have been made to establish the impact of critical intima-media thickness (IMT) on narrowing of the lumen of the common carotid artery (CCA). In the present study, sonomorphological criteria have been used to assess how intima-media thickening in the CCA may influence the artery geometry. METHODS: High-resolution ultrasonography was employed in 233 patients (466 arteries) to quantify the selected parameters of CCA biometry: IMT, arterial lumen diameter (LD), interadventitial diameter (IAD), and outer artery diameter (OAD). RESULTS: With an increase of CCA IMT up to the critical point of 1.2 mm, the LD showed parallel compensatory increases. Above the inflection point of 1.3 mm, the lumen became progressively narrower proportionally to the increasing IMT. CONCLUSION: There are limits to the compensatory enlargement of the CCA lumen. Above the inflection point of CCA IMT of 1.3 mm, the artery lumen becomes progressively narrower with increasing IMT.

Carotid Artery Diseases↗

PubMed2004

Limited usefulness of the PFA-100 for the monitoring of ADP receptor antagonists--in vitro experience.

We have evaluated the usefulness of the PFA-100 system (collagen/ADP and collagen/epinephrine cartridges) to assess the in vitro effects of a few platelet function inhibitors: Aspisol (60 microg/ml), 4-[4-[4-(aminoiminomethyl]-1-piperazinyl]-1-piperidineactetic acid, hydrochloride trihydrate (GR144053F, fibrinogen receptor antagonist, 100 nM), adenosine-3',5'-diphosphate (A3P5P, P2Y1 ADP receptor antagonist, 500 microM) and Bis[(adenosine-5'-O-phosphorodithioyl)methylene]-phosphinic acid (APTMPA, P2Y12 ADP receptor antagonist, 500 microM) on platelet function, as compared with the other commonly used diagnostic technique, a whole blood electrical aggregometry (20 microM ADP or 0.5 mM arachidonic acid). The in vitro studies were carried out on a group of 38 subjects. Whereas all the examined platelet antagonists and inhibitors almost completely blocked the 20 microM ADP- or 0.5 mM arachidonic acid-induced (in the case of acetylsalicylic acid) whole blood aggregation, only two inhibitors (Aspisol and GR144053F) remained effective in a significant prolongation of the PFA-100 occlusion time. Otherwise, using the PFA-100 system we were not able to detect the inhibitory actions of ADP receptor antagonists- P2Y1 and P2Y12. Our findings point to a limited usefulness of the PFA-100 system for the monitoring of the effectiveness of ADP receptor antagonists. The outcomes of this study show that platelet aggregometry in whole blood is characterised by the highest sensitivity in the monitoring of the investigated blood platelet inhibitors.

Adenosine Diphosphate↗