Low protein Z levels, but not the intron F G79A polymorphism, are associated with unexplained pregnancy loss

Introduction

The present case-control study was designed in order to investigate the association between plasma protein Z (PZ) levels, the intron F G79A polymorphism and unexplained pregnancy loss.

Materials and Methods

51 women with at least two consecutive or three non-consecutive fetal losses between the 8th and 12th week of gestation and 47 apparently healthy parous women of reproductive age with no history of pregnancy loss (controls) were enrolled. Allele frequencies of the PZ intron F G79A polymorphism and PZ levels were measured.

Results

PZ levels (mg/L) were significantly lower in cases (mean±S.D. 1.28 ± 0.56) than controls (1.97 ± 0.76, p < 0.001) and in carriers of the A allele (1.46 ± 0.62), compared to GG homozygous subjects (1.72 ± 0.81, p = 0.044). A higher proportion of cases (41.2%) were PZ-deficient (< 1 mg/L), compared to controls (10.6%, p = 0.001). No significant difference in the frequency of at least one A allele carriers was observed between cases (39.2%) and controls (40.4%).

Conclusion(s)

It is possible that low PZ levels are a novel risk factor for unexplained recurrent miscarriage or fetal death. The presence of the F 79A allele is associated with significantly lower PZ levels, but, in the present study, was unrelated to unexplained early pregnancy loss.     

The temporal relationship between growth hormone and slow wave sleep is weaker after menopause

Objective

To study the temporal association between growth hormone (GH) and slow wave sleep (SWS) in middle-aged women.

Methods

Seventeen premenopausal and 18 postmenopausal women were studied using all-night polygraphic sleep recordings and blood sampling at 20-min intervals. The postmenopausal women were re-studied after six months on hormone therapy (HT) according to a randomized, double-blind, placebo-controlled protocol.

Results

The total sleep time (premenopausal 361.9 ± 81.5 min, postmenopausal 358 ± 67.7 min) and the percentages of the sleep stages did not differ between pre- and postmenopausal women. In postmenopausal women the first GH peak after sleep onset occurred later and with a more variable time interval compared to premenopausal women. The percentage of SWS was highest 40-20 min prior to the first GH peak after sleep onset in both groups with a higher SWS proportion in premenopausal women (p = 0.048), although the total SWS percent for night did not differ. HT did not affect the distribution of SWS in postmenopausal women.

Conclusions

The temporal relationship between GH and SWS in premenopausal women is less robust after menopause and is not improved with HT.     

The impact of selective and non-selective non-steroid anti-inflammatory drugs on secondary hemostasis in healthy volunteers

Background

Clinical and epidemiological studies have associated selective COX-2 inhibitors with an increased risk of cardiovascular events. There are no clinical studies on the possible effects of these drugs on secondary hemostasis. The hypothesis for this study is that the use of selective COX-2 inhibitors could affect the secondary hemostasis and by that increase the risk of cardiovascular events in a population at high risk.

Methods

An open-label randomized cross-over study was performed in 20 healthy male volunteers. The study consisted of two periods of each 21 days with medication, either celecoxib 100 mg b.i.d. or naproxen 250 mg b.i.d. Treatment periods were separated by a washout period of 28 days. Blood samples were obtained before the first medication period, and at the end of each medication period. Primary effect parameter was FXII level. Secondary effect parameters included a wide range of coagulation factors involved in secondary hemostasis.

Results

There was no statistically significant effect of celecoxib or naproxen on the primary effect parameter. Protein C activity was significantly decreased after treatment with naproxen (P < 0.01), compared to baseline. Platelet function, demonstrated as closure time (CT), was at baseline 118 ± 24 sec. (mean ± SD). Naproxen prolonged CT to 171 ± 50 sec. (P < 0.001). Celecoxib did not change CT significantly (119 ± 24 sec.).

Conclusions

Neither the selective COX-2 inhibitor celecoxib, nor the non-selective NSAID naproxen caused any change in the primary effect parameter from the secondary hemostasis.     

Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function

Introduction

Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls.

Materials and Methods

Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (± 5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean±SEM.

Results

Twenty cases (mean age 42 ± 4.0 years, 11 females) and 39 controls (mean age 41 ± 2.9, 22 females) were studied. FMD was 5.7 ± 0.8% in cases (95% CI: 4.1 to 7.3) and 6.8 ± 0.5% (5.7 to 7.9) in controls (p = NS). Plasma von Willebrand factor was 128 ± 11.3% and 134.2 ± 16.1% in cases and controls, respectively (p = NS). Soluble P-selectin and soluble CD40L were 94.1 ± 4.9 ng/ml and 0.7 ± 0.1 ng/ml in cases and 87.7 ± 4.0 ng/ml and 1.0 ± 0.2 in controls, respectively (p = NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups.

Conclusions

Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system.     

Haemostatic profile of healthy premature small for gestational age neonates

Background

The pathogenetic profile of premature Small for Gestational Age (SGA) neonates is strongly related to their haemostatic equilibrium, which is inadequately understood.

Objective

To evaluate coagulation and fibrinolysis in premature SGA neonates before intervening with Vitamin K administration.

Study design

We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born prematurely [gestational age (G.A.) < 37 weeks]. Study population consisted of 139 preterm newborns, 68 of whom were SGA (25 males and 43 females), while 71 were AGA (37 males and 34 females) that consisted the control group. Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test and the Mann-Whitney U test were used to compare the differences between the values of haemostatic parameters.

Results

Premature SGA infants presented significantly lower levels of fibrinogen (p < 0.029) and higher levels of VIIIc factor, APCR, tPA and PAI-1 (p < 0.041, 0.017, 0.021 and 0.019 respectively). The two groups had similar demographic characteristics (except from birth weight), without significant differences in the values of other haemostatic parameters.

Conclusions

Despite the statistically significant differentiation in the levels of fibrinogen, VIIIc factor, APCR, tPA and PAI-1, the rest of haemostatic parameters have similar values between SGA and AGA preterms.     

Cost of acute ischemic and hemorrhagic stroke in Turkey

Objective

The aim of this study is to examine the direct medical costs and outcomes of patients with stroke.

Material and methods

The records of the patients admitted with ischemic and hemorrhagic stroke to the University of Trakya, School of Medicine, Department of Neurology were reviewed retrospectively in year 2007. Direct medical costs (total costs, radiological, laboratory, medicine, and other) were calculated, additionally cost per life saved and per life-year saved were calculated for stroke patients.

Results

The study group consisted of 328 patients (169 male/159 female) and mean age was 66.5 ± 12.4 years. Length of hospital stay was 10.7 ± 7.5 days. Mortality rate was 20.4% and the mRS score of the patients was 3.2 ± 2.1. The average cost of stroke was US$ 1677 ± 2964 (29.9% medicine, 19.9% laboratory, 12.8% neuroimaging, and 38% beds and staff). Cost per life saved and per life-year saved were US$ 2108 and US$ 1070, respectively.

Conclusion

This is the first study in order to determine direct medical cost of stroke in Turkey, therefore, it may be guideline for disease-cost management of stroke.     

Vitamin D and multiple sclerosis. A prospective survey of patients of Poitou-Charentes area

Introduction

Recent reports demonstrate the implication of vitamin D in multiple sclerosis (MS).

Methods

In a multicentric regional study (Poitou-Charentes area) during the first trimester 2010, we measured the 25-OH vitamin D serum level in 170 consecutive MS patients, and in 170 controls matched for age (± 4 years), sex and date of blood sample analysis. We searched for correlations between 25-OH vitamin D serum levels and the MS form, the disability (EDSS), the relapse rate during the previous year and the presence and number of enhancing lesions on T1-weighted MRI dating less than 12 months in relapsing MS.

Results

Hypovitaminosis D was very frequent in MS patients and 25-OH vitamin D serum level was significantly lower (14,5 ± 9,2 mcg/mL) in MS patients than in the control group (16,7 ± 9,6 mcg/mL). This serum level was inversely correlated with the degree of disability measured with EDSS score and was lower in secondary progressive (RR-SP) and primary progressive (PP) MS than in relapsing MS (RR). No correlation was found between 25-OH vit D serum level and relapse rate during the previous year in RR MS and the presence and number of enhancing lesions on T1-weighted MRI dating from less than 12 months.

Conclusion

25-OH vit D serum level is very low in MS, mainly in RR-SP and PP MS and is correlated with disability. This suggests MS patients should be screened for vitamin D deficiency and given supplementation systematically when hypovitaminosis D is discovered.     

Decreased maternal protein S activity is associated with fetal growth restriction

Introduction

Protein S (PS) activity has been shown to decrease during normal pregnancy. The aim of this study was to determine any correlation between decreased maternal PS activity and fetal growth restriction (FGR).

Methods

We carried out a retrospective study of maternal PS activity and complement 4b-binding protein (C4BP) concentration in 102 patients with FGR and 58 patients with fetuses that had normal growth. Among pregnancies affected by FGR, 14 diagnoses were made in the second trimester and 88 in the third trimester. Patients whose fetuses had normal growth were matched with FGR subjects for maternal age and gestational age at sampling (29 cases each in the second and third trimester).

Results

Mean PS activity of the control group in the third trimester was significantly lower than in the second trimester (56.5 ± 16.5% vs 35.8 ± 13.8%). PS activity in women with FGR was significantly decreased in both the second trimester (36.6 ± 13.2%) and third trimester (30.2 ± 12.2%) compared with control group levels. Plasma concentrations of C4BP for the control group were significantly higher in the third trimester than in the second trimester (90.5 ± 17.5% vs 81.1 ± 13.6%). However, in women with FGR, plasma C4BP concentrations in both the second trimester (84.0 ± 14.8%) and the third trimester (86.0 ± 17.7%) were comparable with concentrations of the control group.

Conclusions

Maternal PS activity decreased as normal pregnancies progressed but decreased over time in cases with FGR. Excessive decreases in PS activity during pregnancy could contribute to development of FGR.     

Detection of endogenous tissue factor levels in plasma using the calibrated automated thrombogram assay

Background

The calibrated automated thrombogram (CAT) assay measures thrombin generation in plasma.

Objective

Use the CAT assay to detect endogenous tissue factor (TF) in recalcified platelet-rich plasma (PRP) and platelet-free plasma (PFP).

Methods

Blood from healthy volunteers was collected into citrate and incubated at 37 °C with or without lipopolysaccharide (LPS) for 5 hours. PRP and PFP were prepared and clotting was initiated by recalcification. Thrombin generation was measured using the CAT assay.

Results

The lag time (LT) was significantly shortened in PRP prepared from LPS-treated blood compared with untreated blood (10 ± 3 min versus 20 ± 6 min), and this change was reversed by the addition of inactivated human factor VIIa. LPS stimulation did not change the peak thrombin. Similar results were observed in PFP (21 ± 4 min versus 35 ± 5 min). LPS stimulation also significantly reduced the LT of PRP and PFP derived from blood containing citrate and a factor XIIa inhibitor. Finally, a low concentration of exogenous TF shortened the LT of PFP prepared from unstimulated, citrated blood without affecting the peak thrombin.

Conclusion

Changes in LT in the CAT assay can be used to monitor levels of endogenous TF in citrated plasma.     

Risk of deep venous thrombosis (DVT) in bedridden or wheelchair-bound multiple sclerosis patients: A prospective study

Background

Multiple sclerosis (MS) often causes progressive loss of mobility, leading to limb paralysis. Venous and lymphatic stasis is a risk condition for venous thromboembolism (VTE). There is, however, no data on the frequency of VTE complicating the progression of MS. The aim of this study was to assess the frequency of deep vein thrombosis (DVT) in patients with late-stage MS attending a neurology center for rehabilitation.

Patients and Methods

A total of 132 patients with MS were enrolled, 87 women and 45 men, mean age 58 ± 11 years. The disease had started on average 18.7 years before; patients reported 9.6 hours bedridden per day or 14.3 hours wheelchair-bound. Only 25 patients reported a residual ability to walk alone or with help. Lower limb edema was present in 113 patients, bilateral in 41 cases. At admission all patients underwent extended compression ultrasonography. Their plasma D-dimer levels were measured. No antithrombotic prophylaxis was given.

Results

DVT was found in 58 patients (43.9%); 32 had a history of VTE. Forty of these patients (69%) had chronic lower limb edema, in 19 cases bilateral. D-dimer levels in the DVT patients were significantly higher than in patients without DVT (553 ± 678 vs. 261 ± 152 ng/mL, p = 0.0112, Mann-Whitney Test). Nearly half the DVT patients (26, 45%) had high D-dimer levels (701 ± 684 ng/mL). Of the 74 patients without DVT, 48 had normal D-dimer (193.37 ± 67.28 ng/mL) and 26 high (387.61 ± 187.42 ng/mL).

Conclusions

The frequency of DVT in late-stage MS may be over 40%. The long history of the disease means the onset of each episode cannot be established with certainty. A number of patients with positive CUS findings had negative D-dimer values, suggesting a VTE event in the past. However, the level of DVT risk in this series should lead physicians to consider the systematic application of long-term preventive measures.     

Intra- and inter-rater reliability of motor unit number estimation and quantitative motor unit analysis in the upper trapezius

Objective

To collect normative data and assess the intra- and inter-rater reliability of decomposition-enhanced spike-triggered averaging (DE-STA) motor unit number estimation (MUNE) and quantitative MU analysis obtained using decomposition-based quantitative electromyography (DQEMG) in the upper trapezius (UT).

Methods

In 10 control subjects, the experimental protocol was performed twice by the same examiner, and once by a second examiner.

Results

Mean MUNE values were 339 ± 121 (rater 1a), 320 ± 131 (rater 1b), and 262 ± 115 (rater 2) MUs. Intra- and inter-rater reliability was good for maximum CMAP (ICC = 0.77 and 0.79, respectively) and moderate for MUNE (ICC = 0.69 and 0.73, respectively), with poor inter-rater reliability for mean S-MUP (ICC = 0.42). Significant differences between rater 1a and 2 were found for mean S-MUP (p = 0.014) and MUNE (p = 0.002), and moderate to good levels of reliability found for quantitative needle-detected MUP parameters.

Conclusions

Various components of the protocol may have contributed to mean S-MUP variability, and may require particular attention in a large, proximal muscle like the UT.

Significance

This study has established preliminary data using DQEMG in a novel muscle which may be relevant to study in patients with ALS.     

Endogenous thrombin potential (ETP) in plasma from patients with AMI during antithrombotic treatment

Background

The beneficial impact of warfarin in preventing new events after AMI is well established. Decrease in thrombin generation seems to be the key element in anticoagulant treatment.

Objectives

The aims were to investigate the effect of warfarin and platelet inhibition on thrombin generation, assessed by the endogenous thrombin potential (ETP), and study the relation between coagulation parameters and ETP in patients with AMI.

Patients/Methods

In the present sub-study of the WARIS II trial, patients with AMI were randomly assigned to treatment with aspirin 160 mg/d (n = 57), aspirin 75 mg/d and warfarin (INR 2.0-2.5) (n = 68) or warfarin (INR 2.8-4.2) (n = 61). Fasting blood samples were collected from patients at discharge from hospital and after 6 weeks treatment.

Results

Correlation analyses showed that both ETP and peak thrombin levels were significantly correlated with Factor VII Ag (r = 0.38 and 0.36 respectively, p < 0.01 for both) and with F1+2 (r = 0.26 and 0.23 respectively, p = 0.01 for both) at baseline. Antithrombotic treatment for 6 weeks caused a highly significant inhibition of ETP in patients treated with warfarin (− 28% ± 5%, p < 0.001), and patients treated with aspirin/warfarin (− 24% ± 8%, p = 0.04). Similarly, peak thrombin levels were reduced in patients treated with warfarin (− 18% ± 7%, p = 0.049) and aspirin/warfarin (− 19% ± 5%, p = 0.029), whereas an increase (12% ± 4%, p = 0.029) occurred during aspirin treatment alone. F1+2 levels decreased by 64% and 58% in the warfarin and aspirin/warfarin groups, respectively (p = 0.001 for both).

Conclusions

In patients with AMI, warfarin significantly reduced the endogenous thrombin generation and the potential to generate thrombin in plasma ex vivo, whereas aspirin alone had no effect on thrombin generation in vivo or ex vivo, assessed by ETP.     

Activation of coagulation in amniotic fluid during normal human pregnancy

Introduction

Amniotic fluid (AF) is an important medium for fetal development which exhibits high procoagulant activities; however, the role of these procoagulants during pregnancy has not been elucidated and might be associated with pregnancy complications. The current study aimed to evaluate factor X (FX) activation and its association with tissue factor (TF), tissue factor pathway inhibitor (TFPI) and coagulation activation markers in AF during normal human pregnancy.

Methods

Activation of FX and concentration of TF, free TFPI, D-dimer and prothrombin fragments (F1 + 2) were evaluated in AF samples obtained for chromosome analysis from 91 women with normal pregnancy: 65 samples were taken from patients at 16-20 weeks of gestation, 9 samples were drawn at 21-30 weeks and 17 samples−after 30 weeks of gestation.

Results

Activation of FX in AF significantly increased during normal pregnancy (from 65 ± 41 to 205 ± 80 equivalent RVV ng/mg total protein, P < 0.0001). TF and TFPI levels in AF also rose with gestational age. In contrast, the AF concentration of D-dimer and F1 + 2, markers of coagulation activation significantly decreased when expressed per mg total protein. Levels of free TFPI correlated with TF (r = 0.5, P < 0.001), and were 8-fold higher than those of TF during pregnancy.

Conclusion

High levels of TFPI might be associated with the inhibition of procoagulant activity in amniotic fluid during normal pregnancy, which may account for the rarity of clinical amniotic fluid embolism.     

Decreased serum BDNF levels in major depressive patients

Background

Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity. The aim of the present study was to measure serum BDNF levels in depression and to analyze the relationship between BDNF levels and severity of depression.

Methods

Thirty patients meeting the DSM-IV criteria for major depressive disorder and 40 normal control subjects were recruited for this study. Patients had not used psychotropic drugs. The severity of depression was assessed by the Hamilton Rating of Depression Scale (HAM-D). Serum BDNF levels were determined by using ELISA.

Results

HAM-D scores were 17.09 ± 4.96 in depressed patients. We determined that the serum BDNF levels of the depression patients were lower than those of the healthy control group (respectively, 1453.42 ± 144.51 pg/ml, 1632.23 ± 252.93 pg/ml, t = 3.467, p = 0.001, independent t test). No correlation was found between the patients’ serum BDNF levels and HAM-D scores (p > 0.05, Pearson correlation analysis).

Conclusions

Our results suggest that serum BDNF levels are low in depression. However it was not found association between serum BDNF levels and the severity of depression.     

Interictal alterations of cytokines and leukocytes in patients with active epilepsy

Background

Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrome.

Methods

101 patients with active focal or generalized epilepsy were prospectively included and compared to 36 healthy controls. Immuno-phenotype of leukocyte subsets and cytokines IL-1β, IL-6 and tnfα were measured in peripheral blood. Multivariate analyses were performed to test group differences.

Results

As compared to controls, the patients showed an elevated percentage of monocytes (18.06 ± 7.08% vs. 12.68 ± 4.55%, p < 0.001), NK cells (14.88 ± 7.08% vs. 11.43 ± 5.41%, p = 0.019) and IL-6 concentration (3.33 ± 3.11 pg/ml vs. 1.5 ± 1.36 pg/ml, p = 0.002). This remained true when focal epilepsies or generalized epilepsies were compared separately to controls but only focal epilepsies showed additionally a decrease in B lymphocyts (8.16 ± 3.76% vs. 11.54 ± 4.2%, p < 0.001). Treatment with lamotrigine was associated with a higher percentage of B lymphocytes and valproate with an increased percentage of CD4⁺ T lymphocytes. Therapy with levetiracetam showed a trend towards decreased CD8⁺ T cell counts. No significant differences were seen between focal and generalized epilepsies and between temporal and extratemporal lobe epilepsies.

Conclusion

Patients with active epilepsy revealed interictal alterations of the immune system which varied among specific syndromes and were influenced by antiepileptic drug treatment.     

Endothelial haemostatic markers in members of families with familial combined hyperlipidemia

Introduction

The aim of this study was to evaluate the plasma levels of endothelial haemostatic markers - von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA) and soluble thrombomodulin (sTM) — in asymptomatic, nonsmoking members of families with familial combined hyperlipidemia (FCH). We investigated the association between these factors and the intima-media thickness (IMT) of the common carotid artery, selected risk factors of atherosclerosis and markers of insulin resistance.

Methods

82 members of 29 FCH families were divided into two groups: HL (probands and hyperlipidemic first-degree relatives, n = 47) and NL (normolipidemic first-degree relatives, n = 35). The control groups C-HL (n = 20) and C-NL (n = 20) consisted of sex- and age-matched healthy individuals. IMT was measured by ultrasound at a far wall of both common carotid arteries.

Results

Compared with healthy controls, hyperlipidemic subjects had significantly higher levels of vWF (146.4 ± 73.2% versus 112.2 ± 29.4%, p < 0.05), of PAI-1 (102.4[83.0-117.0] ng/ml versus 63.5[31.8-87.3] ng/ml, p < 0.01) and of t-PA (5.1[2.5-7.9] ng/ml versus 3.4[1.4-5.8] ng/ml, p < 0.05). They had increased IMT, which correlated with vWF (r = 0.29, p < 0.05). Their normolipidemic relatives had significantly higher levels of vWF (137.2 ± 42.8% versus 106.6 ± 24.0%, p < 0.01) and of PAI-1 (75.3[53.2-92.0] ng/ml versus 48.6[37.4-85.9] ng/ml, p < 0.05). Levels of vWF, PAI-l and t-PA were independently associated with several markers of insulin resistance.

Conclusions

Asymptomatic members of FCH families have increased endothelial haemostatic factors— vWF, PAI-1, t-PA, which are associated with insulin resistance. VWF correlates with morphological vascular changes, detected by the increase of IMT, presented in only hyperlipidemic subjects.     

Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide attempters and controls

Introduction

Serotonin has been extensively studied in relation to both personality features and suicidal behaviours.

Objective

In this study, we considered the association between the serotonin receptor 1A (HTR1A) and 2C (HTR2C) SNPs and personality traits, as measured by the Temperament and Character Inventory (TCI), in a sample of suicide patients and healthy volunteers.

Methods

The SNPs considered were, for HTR1A rs1423691, rs878567 and rs6295, and for HTR2C rs547536, rs2192372, rs6318, rs2428707, rs4272555 and rs1801412. The sample was composed of three groups: two German samples, consisting of a healthy control group of 289 subjects (42.6% males, mean age: 45.2 ± 14.9) and a psychiatric patient group of 111 suicide attempters (38.7% males, mean age: 39.2 ± 13.6), and an Italian sample, composed of 64 mood disorder patients (35.9% males, mean age: 43.0 ± 14.8). In the German samples all the SNPs were investigated, while in the Italian sample only the HTR1A rs6295 and the HTR2C rs6318 SNPs were considered.

Results

Controlling for sex, age and educational level, single markers and haplotypes were not or only marginally associated with personality dimensions.

Conclusions

Our study does not support the role of HTR1A and HTR2C gene variants on personality traits in both healthy volunteers and mood disorder patients.     

Characterisation and reproducibility of a human ex vivo model of thrombosis

Background

The Badimon chamber is a clinical ex vivo model of thrombosis that mimics flow conditions within the coronary circulation of man. The aims of this study were to characterise thrombus formation in the chamber and evaluate its reproducibility.

Methods

Using blood from 24 healthy human volunteers, thrombus formation was assessed at low and high shear rates with porcine aortic tunica media as the thrombogenic substrate. Thrombus area was measured histomorphometrically. Reproducibility was assessed by paired measurements made both within and between days. Platelet activation was assessed before and at selected points within the extracorporeal circuit using flow cytometry, and fibrin content and distribution within the thrombus were assessed by immunohistochemistry.

Results

Total thrombus area was highly reproducible within and between days in the low shear ([mean thrombus area, mean difference ± SEM] 8,018 μm², 58 ± 204 μm² and 8,177 μm², -154 ± 168 μm² respectively) and high shear chambers (11,802 μm², -52 ± 175 μm² and 11,877 μm², 220 ± 181 μm² respectively). Total thrombus area was greater in the high compared to the low shear chamber (11,970 ± 285 μm²versus 7,892 ± 298 μm²; P < 0.0001). Transit through the extracorporeal circuit did not result in platelet activation which was only detected after blood passed across the perfusion chambers (P = 0.02 for platelet-monocyte aggregate formation and P = 0.05 for P-selectin expression). Thrombus in the low shear chamber contained a greater proportion of fibrin (25.0 ± 6.0% versus 8.3 ± 1.6%, P < 0.001).

Conclusions

The Badimon chamber provides a highly reproducible technique for the assessment of ex vivo platelet-rich thrombus formation in man.     

Controlled reperfusion with intravenous bivalirudin and intracoronary abciximab combination therapy in the porcine myocardial infarction model

Introduction

The reperfusion injury (RI) remains a significant limitation of primary PCI, therefore we evaluated the role of intracoronary abciximab and bivalirudin for anticoagulation on myocardial salvage and RI in the porcine model of ischemia/reperfusion.

Materials and Methods

Myocardial infarction was induced in 23 pigs by 60-minute over-the-wire (OTW) balloon occlusion of the LAD. Animals received intravenous bivalirudin and then five minutes prior to reperfusion, either a coronary downstream infusion of abciximab (n = 11) or saline (n = 12) through the central lumen of an OTW catheter. All animals were followed for 48 hours.

Results

Histological analysis showed that infarct area (IA) and area at risk (AAR) were comparable between groups (IA/AAR%: 57.6 ± 8% vs. 57.1 ± 7%, p = 0.8). Confirming this trend, biochemical markers (troponin I, TNF-alpha, IL-6, hsCRP, adiponectin, and VCAM) and left ventricular ejection fraction were also similar at 48 hours. Adhesion markers like ICAM and P-selectin were significantly decreased in the study group, nevertheless histological evidence of leukocyte extravasation was similar. The enhancement of apoptosis by TUNEL was comparable in both groups. The number of hemorrhagic infarctions confirmed by micro and macroscopic evaluation tended to be higher in the study group (70% vs. 20%, p = 0.07).

Conclusions

Despite lowered concentrations of adhesion molecules, intracoronary abciximab with peripheral bivalirudin is not superior to bivalirudin unaided in terms of myocardial salvage caused by RI in the porcine ischemia/reperfusion model. This might be due to local hemorrhage caused by abciximab.     

Increased thrombin generation in inflammatory bowel diseases

Background

Inflammatory bowel diseases (IBD) are characterized by an increased thrombotic risk of uncertain etiology. Endogenous thrombin potential (ETP), a parameter of the thrombin generation curve, represents a new tool in the evaluation of thrombotic and bleeding disorders.

Aims

To study ETP in IBD patients and to correlate the results with clinical and biochemical features.

Methods

Seventy-four IBD patients (37 ulcerative colitis and 37 Crohn's disease) and 74 sex- and age-matched healthy individuals. ETP was measured upon activation of coagulation with small amounts of tissue factor and phospholipids in the presence or absence of thrombomodulin; results were expressed as nM thrombin·minutes.

Results

Mean±SD ETP values were significantly higher in patients (1,499 ± 454) than controls (1,261 ± 385) (p < 0.001) only when the test was performed in the presence of thrombomodulin. ETP evaluated as ratio (with/without thrombomodulin), taken as an index of hypercoagulability, was significantly higher in patients (0.69 ± 0.14) than controls (0.62 ± 0.18) (p < 0.006). Patients with increased C-reactive protein (CRP) had significantly higher mean ETP (1,721 ± 458) than those with normal CRP (1,357 ± 394) or controls (1,261 ± 385) (p < 0.001). Patients who at the time of blood sampling were classified as having a clinically active disease had ETP higher than those who were quiescent (1,655 ± 451 versus 1,388 ± 427, p < 0.001) or controls (1,261 ± 385, p < 0.001).

Conclusions

ETP measured in the presence of thrombomodulin or as ratio (with/without thrombomodulin) is increased in IBD patients, mainly in those with increased CRP or active disease. It may be considered as a candidate test for prospective studies aimed at assessing the risk of thrombosis in IBD patients.