Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha.

BACKGROUND: Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc). OBJECTIVES: This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc. MATERIAL AND METHODS: This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer. RESULTS: The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9). CONCLUSIONS: The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.

Prothrombotic state, endothelial injury, and echocardiographic changes in non-active sarcoidosis patients.

Sarcoidosis is a multisystem inflammatory granulomatous disease of unknown cause that most commonly affects lungs and lymph nodes, with frequent yet asymptomatic cardiac involvement. The epidemiologically associated cardiovascular risk suggests an underlying prothrombotic state and endothelial dysfunction, currently understudied in the available literature. Therefore, we aimed to investigate prothrombotic plasma properties together with selected echocardiographic and laboratory biomarkers of cardiovascular injury in that disease. N = 53 patients with pulmonary sarcoidosis in clinical remission and N = 66 matched controls were assessed for inflammatory and endothelial injury biomarkers, plasma thrombin generation profile, and echocardiographic and lung function parameters. Sarcoidosis cases had impaired systolic and diastolic left ventricular function, higher concentrations of inflammatory markers, D-dimer and factor VIII activity compared to the controls. The coexistence of extrapulmonary disease was associated with elevated circulating vascular cell adhesion molecule 1, while cases with hypercalcemia had higher thrombomodulin concentration. Sarcoidosis was characterized by the unfavorably altered thrombin generation profile, reflected by the 16% higher endogenous thrombin potential (ETP), 24% increased peak thrombin concentration, and 12% shorter time to thrombin peak in comparison to the control group. ETP was higher in cases with proxies of pulmonary restriction, extrapulmonary-extracutaneous manifestation, and need for corticosteroids use. Despite the clinical remission, sarcoidosis is related to prothrombotic plasma properties and signs of endothelial injury, likely contributing to the higher risk of cardiovascular events. In addition, subclinical cardiac involvement may play an additional role, although further clinical and experimental studies are needed to verify these findings.

Genetic Association between TNFA Polymorphisms (rs1799964 and rs361525) and Susceptibility to Cancer in Systemic Sclerosis.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine that plays an important role in the pathogenesis of autoimmune diseases. The aim of the study was to establish an association between TNF-α promoter variability and systemic sclerosis (SSc). The study included 43 SSc patients and 74 controls. Four single nucleotide polymorphisms (rs361525, rs1800629, rs1799724, and rs1799964) located at the promoter of the TNFA gene were genotyped using commercially available TaqMan allelic discrimination assays with real-time PCR. The rs1799724 allele was associated with an increased SSc susceptibility (p = 0.028). In turn, none of the polymorphisms studied were related to the clinical and laboratory parameters of SSc patients, except for a higher prevalence of anti-Ro52 antibodies in the AG rs1800629 genotype in comparison to GG carriers (p = 0.04). Three of four cancer patients had both CT rs1799964 and AG rs361525 genotypes; thus, both of them were related to the increased risk of cancer, as compared to the TT (p = 0.03) and GG carriers (p = 0.0003), respectively. The TNFA C rs1799724 variant is associated with an increased risk of SSc, while the CT rs1799964 and AG rs361525 genotypes might enhance cancer susceptibility in SSc patients, although large observational and experimental studies are needed to verify the above hypothesis.

The Associations of Perceived and Oxidative Stress with Hypertension in a Cohort of Police Officers.

PURPOSE: Associations between perceived stress and oxidative stress marker and metabolic syndrome (MetS) components were investigated in a cohort of police officers. METHODS: Cross-sectional data from a cohort of non-diabetic subjects (n=233; 19F), median [interquartile range] age 50 [37-44] years, were analysed. MetS was construed in line with International Diabetes Federation (IDF) criteria and perceived stress with Cohen's 10-item Perceived Stress Scale. Plasma oxidative stress marker (free 8-iso-prostaglandin F2α; 8-iso-PGF2α), presence of coronary plaque, carotid artery intima-media thickness (cIMT), and physical activity level were also determined. RESULTS: Obesity was established in 100 (42.92%), hypertension in 111 (47.64), whereas MetS was identified in 104 (44.63%) of the study subjects. A significant difference (p=0.003) in plasma 8-iso-PGF2α level, depending on the MetS components status, was noted. The associations of perceived stress with plasma 8-iso-PGF2α level and the select study variables were gender-specific. In multivariate analysis (adjusted for age and current smoking), positive associations of plasma 8-iso-PGF2α levels with PSS score (B=0.108, 95% CI [0.008, 0.209], p=0.03) and systolic blood pressure (B=0.029, 95% CI [0.003, 0.057], p=0.02) in men only were established. Both the perceived stress (OR 1.101, 95% CI [1.001-1.202], p=0.03) and plasma 8-iso-PGF2α levels (OR 1.223, 95% CI [1.046-1.432], p=0.01) impacted the prevalence of hypertension. Out of the MetS components, the effect of waist circumference (OR=1.138, 95% CI [1.064-1.218], p=0.0001) and glucose (B=2.696, 95% CI [1.081-6.725], p=0.03) were also encountered. No such associations were noted in women, though, neither in univariate nor in multivariate analyses. The prevalence of coronary plaque (0.001), obesity (p<0.001), hypertension (p<0.001) and median cIMT value (p=0.005), as well as leisure-time (p=0.04) and total walking physical activity (p=0.03), differed significantly between the subgroups stratified by MetS components status. CONCLUSION: Both the perceived and oxidative stress were found instrumental in promoting hypertension in a cohort of police officers under study, whereas all study outcomes were conclusively gender-related.

Direct oral anticoagulants in the prevention of stroke in breast cancer patients with atrial fibrillation during adjuvant endocrine therapy: A cohort study.

BACKGROUND: Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral anticoagulants (DOACs) in breast cancer women. METHODS: In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 [interquartile range 56-69] years, CHA2DS2-VASc 2 [2,3]) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack [TIA], venous thromboembolism [VTE]) and bleeding events (major and clinically relevant non-major bleeding [CRNMB]) were recorded in follow-up. RESULTS: During a median follow-up of 40 (interquartile range 28-50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 [29-33]) vs. 26 [24-29]) kg/m2, p = 0.02) and CHA2DS2-VASc score (3 [3]) vs. 2 [1-3]), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 [2.3%/year], rivaroxaban, n = 3 [5.22%/ year], and dabigatran, n = 2 [4%/ year]). No death was related to bleeding. CONCLUSIONS: This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.

Endothelial dysfunction in patients with systemic sclerosis.

INTRODUCTION: Patients with systemic sclerosis experience endothelial dysfunction and damage even in the absence of clinical manifestations. AIM: To evaluate various methods for assessing the endothelial function for their applicability to clinical practice. MATERIAL AND METHODS: Forty-two patients (7 men and 35 women) with systemic sclerosis and 36 controls (11 men and 25 women) matched for age, sex, body mass index, smoking habit, and comorbidities were enrolled in the study. We assessed each participant for typical risk factors for cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1) and thrombomodulin together with flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. RESULTS: Patients with systemic sclerosis did not differ from controls in serum levels of VCAM-1 and thrombomodulin, however, the statistical analysis with adjustment for potential confounders revealed increased levels of thrombomodulin in the patients (p = 0.03). They also had a 45% lower relative increase of FMD (FMD%), and 13% higher IMT (p < 0.01, both, also after adjustment for potential confounders). In a simple regression model, lower FMD% was determined by age (ß = -0.57, 95% confidence interval (CI): -0.72 to -0.43) and C-reactive protein levels (ß = -0.38, 95% CI: -0.55 to -0.22). Thicker IMT was related to age (ß = 0.64, 95% CI: 0.52-0.67), glomerular filtration rate (ß = -0.34, 95% CI: -0.5 to -0.18), and blood thrombomodulin levels (ß = 0.45, 95% CI: 0.13-0.76). CONCLUSIONS: Patients with systemic sclerosis present with endothelial dysfunction which may be detected using ultrasonographic methods. The exact mechanism of observed abnormalities is unknown, but it is possibly related to the chronic inflammation and ischemia-reperfusion injury.

Potential roles of psychological and oxidative stress in insulin resistance: a cohort-based study.

BACKGROUND: The present study investigated the relationships between psychological stress indices and oxidative stress marker, also when combined with emergent insulin resistance (IR), in the non-diabetic, middle-aged subjects, exposed to frequent/chronic psychological stressors. METHODS: Cross-sectional data from a cohort of non-diabetic police officers (n = 234; 19F), aged 27-56 years, were used. Plasma inflammatory (CRP, TNF-α), oxidative stress (free 8-iso-prostaglandin F2α; 8-iso-PGF2α) markers, and insulin were measured. The value of homeostasis model assessment of IR index (HOMA-IR) was assumed the threshold value of IR, i.e. 2.04. Free cortisol in urine and perceived stress (psychological stress indices) were also measured. RESULTS: In the IR subjects, most biochemical variables, inflammatory markers and urine cortisol were significantly higher, as compared to the non-IR ones. Psychological stress indices were associated with plasma 8-iso-PGF2α [B = 0.139, 95% CI (0.048, 0.230), p = 0.002, and B = 0.007, 95% CI (0.0006, 0.014), p = 0.03; for perceived stress level and cortisol, respectively]. Positive associations were established between plasma 8-iso-PGF2α [B = 0.069, 95% CI (0.016-0.120), p = 0.01] and urine cortisol [B = 0.003, 95% CI (0.0003, 0.005), p = 0.02] with HOMA-IR. Metabolic syndrome, as defined by IDF criteria, was established in 110 study subjects, whereas 136 of them were hypertensive. Waist circumference [B = 0.056, 95% CI (0.039, 0.074), p < 0.0001], and systolic blood pressure [B = 0.009, 95% CI (0.00003, 0.018), p = 0.04] were positively associated with HOMA-IR, whereas the association of HDL cholesterol [B = - 0.597, 95% CI (- 1.139, - 0.055), p = 0.03] was a negative one. Cortisol [OR = 1.007, 95% CI (1.002, 1.012), p = 0.006], and 8-iso-PGF2α [OR = 1.103, 95% CI (1.010, 1.201), p = 0.02] affected the incidence of IR. After adjustment for metabolic syndrome (or its components), age, sex, and current smoking, the effects became non-significant. Out of metabolic syndrome components, waist circumference [OR 4.966, 95% CI (2.29, 10.751), p = 0.00004] and hypertriglyceridemia [OR 1.993, 95% CI (1.063, 3.736), p = 0.03] increased the chance of IR incidence. CONCLUSIONS: Both psychological stress indices were associated with oxidative stress, but only cortisol with HOMA-IR. In the subjects exposed to frequent/chronic psychological stressors, cortisol and oxidative stress marker affected IR incidence, being statistically attenuated, though, following adjustment for metabolic syndrome, or its components.

Endothelial dysfunction in patients with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of vasculitis associated with asthma and eosinophilia. Endothelial dysfunction has been well documented in other types of vasculitis but not in EGPA. Thirty patients (10 men and 20 women) diagnosed with EGPA and remaining in a remission, and 58 controls (24 men and 34 women) matched for age, sex, and body mass index, were enrolled in the study. We assessed each participants for typical risk factors of cardiovascular diseases and measured serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also measured flow-mediated dilatation (FMD) of the brachial artery and intima-media thickness (IMT) of the common carotid artery using ultrasonography. Patients with EGPA had 20% higher serum level of VCAM-1 (p < 0.001) and 41.9% of thrombomodulin (p < 0.001). They also had 38.8% lower relative increase of FMD (FMD%) (p < 0.001), indicating endothelial dysfunction. These differences remained significant also after adjustment for potential confounders. Laboratory and ultrasonographic parameters of endothelial injury were correlated to the markers of inflammation and impaired kidney function. Determinants of lower FMD% in a simple regression model were pack-years of smoking (ß = - 0.3 [95% confidence interval (CI) - 0.5 to - 0.1]), serum level of IL-6 (ß = - 0.36 [95% CI - 0.62 to - 0.1]), and thrombomodulin (ß = - 0.34 [95% CI - 0.6 to - 0.08]). EGPA patients are characterized by inflammatory endothelial injury that is likely related to the pathogenesis of the disease. Proper immunosuppressive treatment is the best method to prevent atherosclerosis and future cardiovascular events, the patients may also benefit from additional preventive interventions.

Acquired Haemophilia A Associated with Subsequent Hepatocellular Carcinoma.

Acquired haemophilia A (AHA) is a rare autoimmune disease caused by antibodies directed against clotting factor VIII. About half of cases are idiopathic, but AHA may also be secondary to autoimmune, dermatologic, or oncologic diseases. In approximately 10% of non-idiopathic cases, the disease occurs after or with the diagnosis of cancer as an extremely rare paraneoplastic syndrome. We describe the case of a 73-year-old male patient diagnosed with AHA and successfully treated with recombinant human activated factor VIIa and immunosuppression. Two and a half years later, however, the disease relapsed and a routine ultrasound revealed a liver tumour that was then diagnosed as hepatocellular carcinoma. We present this case to increase awareness that this life-threatening condition may develop years prior to the diagnosis of cancer.

Endothelial dysfunction in patients with granulomatosis with polyangiitis: a case-control study.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors. OBJECTIVE: To evaluate endothelial dysfunction in GPA patients. METHODS: 44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant's serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography. RESULTS: Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (p = 0.01), 66% of IL-6 (p < 0.001) and 50.9% of thrombomodulin (p < 0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (p < 0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (ß = - 0.18 [95% CI: - 0.32 to - 0.04]), C-reactive protein (ß = - 0.17 [95% CI: - 0.27 to - 0.07]), IL-6 (ß = - 0.29 [95% CI: - 0.39 to - 0.19]), blood creatinine level (ß = - 0.2 [95% CI: - 0.3 to - 0.1]), and IMT (ß = - 0.14 (- 0.24 to - 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%. CONCLUSION: GPA is characterized by endothelial dysfunction. FMD is a useful tool for the detection of endothelial injury.

The Relationship of Metabolic Syndrome with Stress, Coronary Heart Disease and Pulmonary Function--An Occupational Cohort-Based Study.

BACKGROUND AND AIMS: Higher levels of stress impact the prevalence of metabolic syndrome (MetS) and coronary heart disease. The association between MetS, impaired pulmonary function and low level of physical activity is still pending assessment in the subjects exposed to stress. The study aimed to examine whether higher levels of stress might be related to MetS and the plaque presence, as well as whether MetS might affect pulmonary function. DESIGN AND METHODS: The study embraced 235 police officers (mean age 40.97 years) from the south of Poland. The anthropometrics and biochemical variables were measured; MetS was diagnosed using the International Diabetes Federation criteria. Computed tomography coronary angiography of coronary arteries, exercise ECG, measurements of brachial flow-mediated dilation, and carotid artery intima-media thickness were completed. In order to measure the self-perception of stress, 10-item Perceived Stress Scale (PSS-10) was applied. Pulmonary function and physical activity levels were also addressed. Multivariate logistic regression analyses were applied to determine the relationships between: 1/ incidence of coronary plaque and MetS per se, MetS components and the number of classical cardiovascular risk factors, 2/ perceived stress and MetS, 3/ MetS and pulmonary function parameters. RESULTS: Coronary artery atherosclerosis was less associated with MetS (OR = 2.62, 95%CI 1.24-5.52; p = 0.011) than with a co-existence of classical cardiovascular risk factors (OR = 5.67, 95% CI 1.07-29.85, p = 0.03; for 3 risk factors and OR = 9.05; 95% CI 1.24-66.23, p = 0.02; for 6 risk factors, respectively). Perceived stress increased MetS prevalence (OR = 1.07, 95% CI 1.03-1.13; p = 0.03), and impacted coronary plaque prevalence (OR = 1.05, 95% CI 1.001-1.10; p = 0.04). Leisure-time physical activity reduced the chances of developing MetS (OR = 0.98 95% CI 0.96-0.99; p = 0.02). MetS subjects had significantly lower values of certain pulmonary function parameters. CONCLUSIONS: Exposure to job-specific stress among police officers increased the prevalence of MetS and impacted coronary plaque presence. MetS subjects had worse pulmonary function parameters. Early-stage, comprehensive therapeutic intervention may reduce overall risk of cardiovascular events and prevent pulmonary function impairment in this specific occupational population.

[Severe dilated cardiomyopathy as a complication of well controlled Churg-Strauss syndrome]. / Ciezka kardiomiopatia rozstrzeniowa jako powiklanie lagodnie przebiegajacego zespolu Churga−Strauss.

We present a case of a 42 year-old male with Churg-Strauss syndrome (CSS), who despite clinical remission developed severe dilated cardiomyopathy. Intensified immunosuppression helped to improve heart function. As heart involvement in CSS is very common, and may occur without prior symptoms, magnetic resonance imaging is advisable to identify patients with heart damage and introduce proper treatment.

Multimodality assessment of cardiac involvement in Churg-Strauss syndrome patients in clinical remission.

BACKGROUND: Cardiac involvement in Churg-Strauss syndrome (CSS) is not uncommon, but its frequency varies widely and may depend on the activity of the disease. Therefore, the cardiac involvement in CSS patients in clinical remission was assessed in the present study. METHODS AND RESULTS: In 20 CSS patients in remission and 20 sex- and age-matched healthy controls, an ECG stress test, echocardiography, and 24-h ECG Holter monitoring were performed, together with cardiac magnetic resonance imaging (cMRI). Cardiac involvement was present in 90% (18/20) of CSS patients. Left ventricular ejection fraction (LVEF) was on average lower in the CSS group than in controls (P<0.05), with 7 patients showing systolic heart failure (LVEF <50%). cMRI changes included late gadolinium enhancement lesions in the LV in 89% of patients (17/19), present in all layers of the myocardium. Signs of ongoing inflammation (early gadolinium enhancement) and edema (T2-weighted imaging) were present in 6/19 patients. Holter monitoring revealed both supraventricular and ventricular arrhythmias more frequently in CSS patients when compared with controls (P<0.05). Absolute eosinophil count before the initiation of treatment was higher in rhythm disturbances (P<0.05), and inversely correlated with LV systolic function (rho -0.65). CONCLUSIONS: Heart involvement in CSS patients who are in clinical remission is very common. It is characterized not only by fibrosis, but also by an active inflammatory process. The latter finding might influence therapeutic decisions in CSS patients in full clinical remission.

[Congestive cardiomyopathy and left intraventricular thrombus as a manifestation of Churg-Strauss syndrome]. / Kardiomiopatia zastoinowa i skrzeplina w lewej komorze jako manifestacje zespolu Churga i Strauss.

A case of a 38-year-old female with symptomatic Churg-Strauss syndrome and congestive cardiomyopathy, complicated by cardiac arrest and left ventricular thrombus formation, is presented. Prompt institution of low molecular weight heparin and steroids resulted in rapid thrombus lysis and improvement of systolic left ventricular function.

The additive antiplatelet action of clopidogrel in patients with coronary artery disease treated with aspirin.

We searched for additional anti-platelet effects of clopidogrel in coronary artery disease (CAD) patients treated with aspirin. Response to clopidogrel was also stratified according to aspirin resistance. Out of 76 screened aspirin-treated CAD male patients, five were aspirin-resistant based on arachidonic acid (AA) and ADP aggregometry. These five patients and 15 aspirin-sensitive patients entered the proper study. Platelet function was assessed at baseline and after one week of additional clopidogrel treatment using aggregometry, flow cytometry (ADP, TRAP-6) and platelet reactivity index (PRI) based on VASP (vasodilatorstimulated phosphoprotein) expression. We evaluated the same markers in 15 healthy men after aspirin treatment. In healthy subjects aspirin did not affect resting or ADP-induced activated GPIIb/IIIa and P-selectin expression. The P-selectin expression on ADP-activated platelets was increased (p < 0.01) in aspirin treated ASA-resistant CAD patients as compared to ASA-sensitive group or aspirin-treated healthy subjects. Clopidogrel significantly decreased ADP and AA-induced platelet aggregation and overcame aspirin resistance in four of five patients. Expression of ADP-induced activation markers was significantly lowered after clopidogrel in all patients. Out of 20 patients, five did not respond to clopidogrel (<10% inhibition of ADP aggregation), and this group showed no change in expression of ADP-induced activation markers after clopidogrel. Clopidogrel treatment significantly reduced PRI only in the clopidogrel-sensitive group. In conclusion, the addition of clopidogrel to aspirin provides greater inhibition of platelets and can overcome aspirin resistance. Flow cytometric analysis of platelets is useful for monitoring of clopidogrel therapy.

[Hereditary hemochromatosis: molecular diagnosis and effect of treatment]. / Rodzinna hemochromatoza--mozliwosci diagnostyki molekularnej i wyniki leczenia.

Hereditary hemochromatosis is a genetic disorder, inherited as an autosomal recessive trait, characterized by iron overload. A single mutation (C282Y) in the HFE gene is found in more than 90% of these patients. We report the case of a 50-year-old man, with clinical symptoms of hemochromatosis, who was found to be homozygous for the C282Y mutation. We present the results of therapeutic phlebotomy after one year of the treatment. Genetic tests were performed on the patient's close relatives and revealed that his son was also homozygous for the C282Y mutation. Early phlebotomy could prevent iron deposition and organ damage in this patient. Genetic determining of the HFE mutations is a useful noninvasive method of diagnosing hereditary hemochromatosis.

[Myocardial infarction as an initial symptom of antiphospholipid syndrome, factor V Leiden mutation, and hyperhomocysteinemia]. / Zawal serca jako przejaw pierwotnego zespolu antyfosfolipidowego. Wspóludzial czynnika V Leiden i hiperhomocysteinemii.

We present a case of a 32-year-old male survivor of two myocardial infarctions, without any classic risk factor of atherosclerosis. Laboratory and genetic diagnostic tests revealed primary antiphospholipid syndrome, mutation in blood coagulation factor V (Leiden) and mild hyperhomocysteinemia, which could be predisposing factors for coronary artery occlusions and should especially be considered in a young patient without apparent cardiovascular risk factors. Additional anticoagulation and substitutional treatment of the folic acid, vitamin B6 and B12 are effective and the continues to do well at home 3 years after discharge.

[Cardiac involvement in systemic autoimmune disease]. / Echokardiograficzna ocena serca w ukladowych chorobach tkanki lacznej.

Systemic autoimmune diseases form a diverse group which includes: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, dermato-polymyositis, Wegener's granulomatosis, Sjögren syndrome. Although multisystem involvement is the hallmark of these diseases, the heart seems to be less affected than other organ systems. The aim of the study was to study possible cardiac abnormalities in patients with documented systemic autoimmune diseases and to assess whether there was any relation between antiphospholipid, anti-dsDNA antibodies and myocardial dysfunction findings. 76 patients (53 with SLE, 9 with MCTD, 8 with scleroderma, 6 with Wegener's granulomatosis) were subjected to our study, 69% of these patients manifested cardiac involvement, based on two-dimentional echocardiografic examination (36%--post-inflammatory valvular thickening, 20%--pericardial effusions, 15%--valvular regurgitation, 7%--left atrial enlargement, 5%--left ventricular hypertrophy, 4%--left ventricular dysfunction). None of the patients showed characteristic, acute Libman-Sacks endocarditis, which probably can be explained by chronic corticosteroid-treatment. Clinical evidence of cardiac abnormalities has been observed, in as many as 58% of cases with positive echocardiographic findings. The frequency and extend of cardiac pathology positively correlated with the detection of antiphospholipid antibodies. No such relationship was observed in patients with the presence of very high titers of antinuclear antibodies (anti-dsDNA). In conclusion, our results indicate that echocardiography is a useful method for assessment and monitoring cardiac involvement in the systemic autoimmune diseases.

Anti-phospholipid antibodies and carotid-artery intima-media thickness in young survivors of myocardial infarction.

BACKGROUND: Not all coronary events occur in young individuals with traditional risk factors. In recent years some authors have observed increased prevalence of elevated anti-phospholipid (aPL) antibodies in young patients with myocardial infarction. Also, thickening of the combined arterial intima-media thickness (IMT) of superficial vessels has been identified as an independent risk factor for both stroke and heart attack. The objective of our study was to assess possible association between aPL antibodies and carotid IM thickening in young survivors of myocardial MATERIAL/METHODS: In a case control study we determined IgG and IgM antiphospholipid antibodies by enzyme-immunoassay, and IMT by ultrasonography in 50 male survivors of myocardial infarction under the age of 50, and compared them to 50 healthy controls. RESULTS: Elevated aPL antibody levels (IgG>10 GPL; IgM>20MPL) were detected in 12 of 50 patients (24%) with MI and in 3 of 50 controls (6%). The mean level of aPL antibodies was significantly higher in the patients than in the controls (IgG 9.15+/-3.53 vs 7.69+/-2.98 GMP, p=0.04 and IgM 18.46+/-7.61 vs 12.14+/-5.05 MPL, p<0.01). Patients with MI had a significantly greater IMT than healthy controls (0.9 mm vs 0.6 mm; p<0.01). There was a correlation between aPL and IM thickening (r=0.31; p=0.01). Among coronary risk factors only hypertension (r=0.28; p=0.01) and smoking (r=0.41; p=0.01) showed a relationship with IMT. CONCLUSIONS: The intima-media thickness of the carotid artery and elevated aPL antibodies are strongly associated with the risk of myocardial infarction in young patients.