Serum D-dimer changes and prognostic implication in 2009 novel influenza A(H1N1)

Background

The patients with Influenza A (H1N1) have a higher mortality compared with suffering from seasonal influenza. However, many clinical characteristics are still not clear. In the course of clinical treatment on H1N1, we found there were some apparent abnormal clinical indexes being detected at the preliminary diagnosis for severely ill patients, especially the obvious increasing of D-dimer. D-dimer may be associated with the prognosis of Influenza A (H1N1).

Methods

Patients' clinical data (age, gender, body mass index, primary diseases, etc.) and the preliminary diagnostic clinical indexes including blood creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactic dehydrogenase (LDH), T cell subsets, blood gas analysis, D-dimer, activated partial thromboplastin time (APTT), prothrombin time (PT) and plasma fibrinogen (FG) were retrospectively analyzed.

Results

Compared with the non-respiratory failure group, the cases in respiratory failure group, especially in death sub-group have lower lymphocytes, higher LDH and D-dimer, as well as decreasing oxygenation index during the preliminary diagnosis(P < 0.05). The disease severity (Apche II scores) was independently associated with preliminary oxygenation index and LDH (R² = 0.511, p < 0.01). The correlation analysis shows that there is a negative correlation between the D-dimer and oxygenation index (r = − 0.510, P < 0.01) in the preliminary diagnosis. Meanwhile, there is also a negative correlation between preliminary diagnostic D-dimer and the lowest oxygenation index after admission (r = − 0.573, P < 0.01).

Conclusions

The peripheral blood lymphocytes (including CD3, CD4 and CD8), LDH, oxygenation index and D-dimer detected in the preliminary diagnosis are important indexes that may affect the disease progress and prognosis of H1N1 patients. The significantly increased D-dimer and corresponding hyoxemia indicate the probability of formation of pulmonary microthrombus. Thus, it may be necessary to consider the anticoagulant therapy.     

Depressive symptoms, perceived social support, and prothrombotic measures in patients with venous thromboembolism

Introduction

Psychosocial factors have been associated with both a prothrombotic state and an increased risk of venous thromboembolism (VTE). We examined the relation of depressive symptoms and social support with D-dimer, an integrative measure of enhanced coagulation activity, and several additional prothrombotic measures in patients with VTE.

Methods

We studied 173 patients with a previous deep venous thrombosis and/or pulmonary embolism (mean age ± SD 45 ± 14 years, 55% men). Clinical and lab assessments took place ≥ 3 months after VTE and ≥ 1 month after discontinuation of oral anticoagulants. The patients rated depressive symptoms and social support by validated questionnaires.

Results

After adjusting for sociodemographic and medical covariates, interactions emerged between depressive symptoms and social support for D-dimer (p = 0.012) and aPTT (p = 0.002). As opposed to patients with high levels of social support, those with low levels of social support showed a direct association of depressive symptoms with D-dimer (r = 0.19, p = 0.014) and an inverse relationship with aPTT (r = -0.14, p < 0.09). Depressive symptoms were associated with levels of thrombin-antithrombin complex (r = 0.19, p = 0.016). Greater social support was associated with prolonged aPTT (r = 0.16, p = 0.046). There were no significant associations of depressive symptoms and social support with D-dimer, fibrinogen, FII:C, FV:C, FVII:C, FVIII:C, FX:C, INR, and thrombin time.

Conclusions

Depressive symptoms are associated with enhanced coagulation activity in patients with VTE, particularly so in those who perceive low levels of social support. Conversely, high levels of social support may contribute directly and through buffering the effect of depressive symptoms to attenuated clotting activity in VTE patients.     

Comparison of levels of inflammatory markers and hemostatic factors in the patients with and without peripheral arterial disease

Introduction

Peripheral arterial disease is one aspect of atherosclerosis, a disease associated with both inflammation and hypercoagulability. Many recent studies have focused on the diversity of mechanisms by which inflammation can promote blood clotting. However, the relationship between plasma concentrations of inflammatory and hemostatic markers and the severity of atherosclerosis is not yet well studied. We want to determine the relations among selected D-dimer, C-reactive protein, fibrinogen, prothrombin time and serum amyloid A, and the ankle brachial index in patients with and without peripheral arterial disease.

Materials and methods

In a prospective cohort study, 45 consecutive patients with peripheral arterial disease of ankle brachial index < 0.90, and 44 patients without peripheral arterial disease of ankle brachial index 0.90 to 1.50 were included. D-dimer, fibrinogen, C-reactive protein, serum amyloid A, and prothrombin time were measured at the recruitment.

Results

Median values of serum amyloid A, D-dimer, and C-reactive protein were significantly higher in the peripheral arterial disease group than in those without peripheral arterial disease group (p < 0.001). The patients with PAD had moderately higher fibrinogen levels than without PAD (p < 0.01). Prothrombin time levels were normal in both groups. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, patients with peripheral arterial disease, levels of serum amyloid A, and C-reactive protein showed a highly significant, inverse association with the ankle brachial index. D-dimer and fibrinogen level increase were also found to be related to lower ankle brachial index, while no association was observed between prothrombin time levels.

Conclusions

Higher C-reactive protein, serum amyloid A, and D-dimer levels are showing positive association with the presence of peripheral arterial disease. C-reactive protein and serum amyloid A levels are direct relations between the ankle brachial index and the extent of vascular inflammation.     

Les atteintes neurologiques au cours du xeroderma pigmentosum

Introduction

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by abnormal sensitivity to sunlight which results in pigmentary changes, telangiectases, keratoses and eventually carcinomata. Additional neurological complications can be associated. The aim of our study was to analyze particularities of neurological abnormalities of Tunisian patients.

Method

We conducted a retrospective study in 62 patients suffering from XP included during the period 1992-2007. Patients were aged from 1 to 64 years (mean age: 17.6 ± 11.4 years). Thirty patients were female and 32 were male. The patients had severe (n = 16), variant (n = 15) and moderate (n = 31) XP.

Results

Neurological abnormalities were observed in 21 patients (33.9%). Mental retardation was observed in 15 of the 21 patients, pyramidal syndrome in five, cerebellar syndrome in two, extrapyramidal syndrome in two, microcephalia in two, choreoatetosis in three cases and a peripheral neuropathy in eight. No neurological disorder was observed in the XP-variant patients. Neurological abnormalities were more frequent in the patients with moderate XP (n = 17, 64.5%) than with severe XP (p = 0.051).

Conclusion

This difference in a group of Tunisian patients confirms the heterogeneous nature of XP and is probably due to genetic heterogeneity.     

Antithrombin III associated with fibrinogen predicts the risk of cerebral ischemic stroke

Background and purpose

The purpose of this study is to examine the feasibility of developing plasma predictive value biomarkers of cerebral ischemic stroke before imaging evidence is acquired.

Methods

Blood samples were obtained from 198 patients who attended our neurology department as emergencies - with symptoms of vertigo, numbness, limb weakness, etc. - within 4.5 h of symptom onset, and before imaging evidence was obtained and medical treatment. After the final diagnosis was made by MRI/DWI/MRA or CTA in the following 24-72 h, the above cases were divided into two groups: stroke group and non-stroke group according to the imaging results. The levels of baseline plasma antithrombin III (AT-III), thrombin-antithrombin III (TAT), fibrinogen, D-dimer and high-sensitivity C-reactive protein (hsCRP) in the two groups were assayed.

Results

The level of the baseline AT-III in the stroke group was 118.07 ± 26.22%, which was lower than that of the non-stroke group (283.83 ± 38.39%). The levels of TAT, fibrinogen, hsCRP were 7.24 ± 2.28 μg/L, 5.49 ± 0.98 g/L, and 2.17 ± 1.07 mg/L, respectively, which were higher than those of the non-stroke group (2.53 ± 1.23 μg/L, 3.35 ± 0.50 g/L, 1.82 ± 0.67 mg/L). All the P-values were less than 0.001. The D-dimer level was 322.57 ± 60.34 μg/L, which was slightly higher than that of the non-stroke group (305.76 ± 49.52 μg/L), but the P-value was 0.667. The sensitivities of AT-III, TAT, fibrinogen, D-dimer and hsCRP for predicting ischemic stroke tendency were 97.37%, 96.05%, 3.29%, 7.89%, but the specificity was 93.62%, 82.61%, 100% and 100%, respectively, and all the P-values were less than 0.001. High levels of D-dimer and hsCRP were mainly seen in the few cases with severe large-vessel infarction.

Conclusions

Clinical manifestations of acute focal neurological deficits were associated with plasma AT-III and fibrinogen. These tests might help the risk assessment of acute cerebral ischemic stroke and/or TIA with infarction tendency in the superacute stage before positive imaging evidence is obtained.     

Comparison of coil types in aneurysm recurrence

Objective

Coiling of saccular aneurysms may result in recurrence requiring retreatment. Aneurysm recanalization may depend on coil type. Coil variations include bare platinum, polymer coated (Matrix), and hydrophylic gel coated (HydroCoil) coils. The effect of coil type on aneurysm recurrence was evaluated.

Methods

Retrospective analysis of prospectively collected database of 100 consecutive, 4-15 mm, coiled, ruptured aneurysms. There were 3 groups based on coil type: (1) bare platinum, (2) HydroCoil, and (3) Matrix. Data collected included age, gender, aneurysm location, follow-up, retreatments and angiographic occlusion and recanalization.

Results

There were 42.4% (n = 14) anterior and 57.5% (n = 19) posterior circulation aneurysms in the bare platinum, 61.5% (n = 16) and 38.45% (n = 10) in HydroCoil, and 43.9% (n = 18) and 56.1% (n = 23) in the Matrix groups. Retreatment was required in 4 (12.1%) bare platinum, 9 (21.9%) Matrix, and 3 (11.5%) HydroCoil groups. On follow-up angiography HydroCoil group had the most number of completely occluded and least number of residual aneurysms (P = 0.01), HydroCoils showed the least (n = 4), bare platinum an intermediate (n = 7), and matrix group the greatest tendency (n = 15) to recanalize.

Conclusions

Matrix coils were most likely to need retreatment. Retreatment rates were comparable for bare platinum and HydroCoils. Follow-up angiography demonstrated statistically significant attenuation of residual aneurysms for HydroCoils. Matrix group had the greatest and HydroCoils the least tendency to recanalize. Factors other than coil surface-coating may attenuate aneurysm recurrence.     

Enhanced hemostatic indices in patients with pulmonary arterial hypertension: An observational study

Background

Pulmonary arterial hypertension (PAH) is a chronic progressive disease characterized by persistent elevation of pulmonary artery pressure. Regardless of the initial trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with PAH are primarily caused by remodeling and thrombosis of small- and medium-sized pulmonary arteries and arterioles, as well as sustained vasoconstriction. Recent studies have emphasized the relevance of several biomarkers of hemostasis in the PAH progression. However, there is no agreement whether hemostatic indices are indeed distinguishing PAH patients from controls.

Methods

Plasma fibrinogen, D-dimer, platelet count, and mean platelet volume, and platelet aggregation induced by ADP and collagen were serially measured in 34 patients with PAH, and 34 matched by age and sex normal volunteers.

Results

Hemostatic indices were significantly higher for fibrinogen (p = 0.0001), D-dimer (p = 0.001), mean platelet volume (p = 0.001), and platelet aggregation induced by ADP-, and collagen (p = 0.0001 for both) in PAH pstients when compared to healthy controls. In contrast, platelet counts were almost identical between both groups.

Conclusions

Patients with PAH exhibit activation of hemostatic indices compared to healthy controls. These data support previous observations that hemostatic abnormalities including platelet activation may directly impact pathogenesis of PAH, and need to be confirmed in larger randomized studies with more comprehensive assessment of hemostatic indices for justification of antithrombotic strategies.     

Rapid antipsychotic response with ziprasidone predicts subsequent acute manic/mixed episode remission

Objective

To assess rapid antipsychotic efficacy with oral ziprasidone monotherapy in bipolar acute manic/mixed episodes with psychotic features, and predictive value of rapid antipsychotic response for subsequent acute manic/mixed episode remission.

Methods

Pooled analysis of two 3-week, randomized, double-blind, placebo-controlled trials of ziprasidone (40-160 mg/d) in inpatients with bipolar I disorder, and a current manic or mixed episode, with (n = 152) or without (n = 246) psychotic features. Psychosis improvement was evaluated by change in SADS-C psychosis score (sum of delusions, hallucinations, and suspiciousness items). Rapid antipsychotic response (?50% decrease in SADS-C psychosis score by Day 4) and acute manic episode response and remission (endpoint ?50% MRS decrease, and a MRS score ? 12, respectively) were analyzed.

Results

Significantly greater antipsychotic effects were observed by Day 4 with ziprasidone treatment (vs. placebo) and the magnitude of improvement increased significantly with time, in all subjects, in the subgroup of all psychotic subjects, and psychotic subjects with low baseline agitation (p < 0.05). Rapid antipsychotic response predicted subsequent acute manic episode remission independent of ziprasidone or placebo treatment received (p < 0.001, ROC AUC = 0.71) with significant improvement in accuracy of MRS remission prediction when compared to models using early changes in MRS score alone (p = 0.01).

Limitations

Post hoc analysis, use of 3 SADS-C psychosis items to assess psychosis.

Conclusions

The predictive value of rapid (Day 4) improvement in psychotic symptoms for subsequent (Day 21) remission of acute manic/mixed symptoms may facilitate enhanced therapeutics, in view of the current practice of brief hospitalization for patients with acute manic/mixed episodes with psychotic features.     

Anticoagulation therapy with combined low dose aspirin and warfarin following mechanical heart valve replacement

Introduction

This study was designed to evaluate safety and efficacy of combined low dose aspirin and warfarin therapy following mechanical heart valve replacement.

Methods

A total of 1 496 patients (686 males, mean age 35 ± 8.5 years) undergoing mechanical heart valvular replacement were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) group. International normalized ratio (INR) and prothrombin time was maintained at 1.8-2.5 and 1.5-2.0 times of the normal value, respectively. Thromboembolic events and major bleedings were registered during follow up.

Results

Patients were followed up for 24 ± 9 months. The average dose of warfarin in the study and control group was 2.92 ± 0.87 mg and 2.89 ± 0.79 mg, respectively (p > 0.05). The overall thromboembolic events in study group were lower than in control group (2.1% vs. 3.6%, p = 0.044). No statistically significant differences were found in hemorrhage events (3.5% vs. 3.7%, p > 0.05) or mortality (0.3% vs 0.4%, p > 0.05) between the two groups.

Conclusions

Following mechanical valve replacement, combined low dose aspirin and warfarin therapy was associated with a greater reduction in thromboembolism events than warfarin therapy alone. This combined treatment was not associated with an increase in the rate of major bleeding or mortality.     

Sex-specific cortisol levels in bipolar disorder and schizophrenia during mental challenge--relationship to clinical characteristics and medication

Objective

Our objective was to examine the cortisol release during a mental challenge in severe mental disorders versus healthy controls (HC), analyzing effects of sex, clinical characteristics and medication, and comparing Bipolar Disorder (BD) to Schizophrenia (SCZ).

Methods

Patients with BD and SCZ (n = 151) were recruited from a catchment area. HC (n = 98) were randomly selected from the same area. Salivary samples were collected before and after a mental challenge and cortisol levels determined.

Results

During the challenge there was an interaction between group and sex (P = 0.015) with male patients having a blunted cortisol release compared to male HC (P = 0.037). Cortisol change did not differ significantly between BD and SCZ. In all patients, the cortisol change correlated with number of psychotic episodes (r = − 0.23, P = 0.025), and in females patients, with number of depressive episodes (r = − 0.33, P = 0.015). Patients using antidepressants had a greater cortisol release during challenge than those not using antidepressants (P = 0.043).

Conclusions

Male patients with severe mental disorders seem to have a uniform abnormal cortisol release during mental challenges which associates with clinical course, and with beneficial effects of antidepressants.     

Enhanced thrombin formation and fibrinolysis during acute Puumala hantavirus infection

Introduction

Nephropathia epidemica (NE) is a viral hemorrhagic fever with renal syndrome associated with thrombocytopenia and mild bleeding. We assessed activation of coagulation and fibrinolysis during the acute phase of NE.

Materials and methods

19 hospital-treated patients were involved. Plasma levels of D-dimer, prothrombin fragments 1 + 2 (F1 + 2), activated partial thromboplastin time (APTT), prothrombin time (PT%), thrombin time (TT), fibrinogen, antithrombin (AT), protein S free antigen (PS), protein C (PC) and complete blood count (CBC) were measured three times during the acute phase and once at 32-54 days after the onset of fever (recovery phase). Laboratory abnormalities were evaluated by the disseminated intravascular coagulation (DIC) scoring advocated by the International Society of Thrombosis and Haemostasis (ISTH).

Results

APTT was prolonged and D-dimer and F1 + 2 increased during the acute phase of NE. AT, PC and PS decreased, and TT was shortened, all implying increased thrombin generation. Acutely F1 + 2 was 3.4-fold and D-dimer even 24-fold higher compared with the recovery phase (median 726 vs 213 pmol/l, and median 4.8 vs 0.2 mg/l, respectively, p < 0.001 for both). Platelet count correlated with AT, PC, and PS (r = 0.73, r = 0.81, and r = 0.71, respectively, p < 0.001 for all) as well as with fibrinogen (r = 0.72, p < 0.001). Only five patients fulfilled the ISTH diagnosis of DIC.

Conclusions

During acute NE thrombocytopenia was associated with decreased natural anticoagulants, shortened thrombin time and enhanced fibrinolysis. Augmented thrombin formation and fibrinolysis characterize this hantavirus infection.     

Differences in findings of nocturnal polysomnography and multiple sleep latency test between narcolepsy and idiopathic hypersomnia

Objectives

To compare differences in nocturnal and daytime polysomnographic findings between narcolepsy (NA) with and without cataplexy (CA) and idiopathic hypersomnia without long sleep time (IHS w/o LST).

Methods

Nocturnal polysomnography (n-PSG) and multiple sleep latency test (MSLT) findings were compared among subjects with NA with CA (n = 52), NA without CA (n = 62), and IHS w/o LST (n = 50).

Results

The NA with CA group had significantly more disrupted and shallower nocturnal sleep than the other groups. On MSLT, the IHS w/o LST group had significantly longer sleep latency (SL) compared with the two NA groups. The latter two groups did not show statistical differences in diurnal variation of SL.

Conclusions

The IHS w/o LST group had milder objective daytime sleepiness compared with the NA groups. In patients with NA, nocturnal sleep disturbances appeared only in cases with CA, despite a similar trend in diurnal changes in sleep propensity between the two NA groups.

Significance

Objective nocturnal sleep disturbances are specific to NA patients with CA, whereas diurnal variations of sleep propensity are observed irrespective of the presence of CA among NA patients. These findings could be helpful for choosing optimal treatment plans for patients with these disorders.     

Feasibility, reliability and validity of the Dutch translation of the Anxiety, Depression And Mood Scale in older adults with intellectual disabilities

Background

The informant-based Anxiety, Depression And Mood Scale was translated into Dutch and its feasibility, reliability and validity in older adults (aged ≥ 50 years) with intellectual disabilities (ID) was studied.

Method

Test-retest (n = 93) and interrater reliability (n = 83), and convergent (n = 202 and n = 787), discriminant (n = 288) and criterion validity (n = 288) were studied. Convergent and criterion validity were studied for the Depressed mood and General anxiety subscales. Subgroups based on level of ID and autism have been made to study the criterion validity. Psychiatric diagnoses based on the PAS-ADD Interview were used as gold standard.

Results

All subscales had good internal consistency (α ≥ 0.80), excellent test-retest reliability (ICC ≥ 0.75) and good interrater reliability (ICC ≥ 0.74), except for the Social avoidance subscale (ICC = 0.57). The Depressed mood subscale showed low correlation (r = 0.44) with the self-report Inventory of Depressive Symptomatology, high correlation with the informant-report Signalizing Depression List for people with ID (r = 0.71) and no correlation with the PAS-ADD's sleep disorders subscale (r = 0.15). Its sensitivity ranged from 73 to 80%, and its specificity from 71 to 79%. The General anxiety subscale showed low correlation with the self-report scales: Glasgow Anxiety Scale (r = 0.37) and Hospital Anxiety and Depression Scale (r = 0.41), and no correlation with the sleep disorder subscale (r = 0.02). Its sensitivity ranged from 67 to 100%, and its specificity from 48 to 81%.

Conclusions

The Dutch translation of the ADAMS is reliable and sufficiently valid to screen for anxiety and depression in older people with ID.     

Enhanced platelet reactivity and thrombosis in Apoe-/- mice exposed to cigarette smoke is attenuated by P2Y12 antagonism

Introduction

Smoking increases the risk of acute arterial thrombosis, including myocardial infarction, likely due to multi-factorial effects on the vasculature. Heightened platelet reactivity may be among the adverse effects of smoke exposure.

Methods

To examine the effects of smoke exposure on platelet function in an atherosclerotic environment, Apoe-deficient female mice, maintained on a Western diet, were exposed (4 hrs/d, 5d/wk) to sidestream cigarette smoke in a whole-body exposure chamber for12 weeks. A separate group of wild type C57BL/6 J mice were also exposed to smoke in an identical fashion.

Results

In comparison to control Apoe-/- mice exposed to filtered ambient air, smoke-exposed Apoe-/- mice displayed a 1.8 ± 0.3 fold enhanced ADP-induced fibrinogen binding ex vivo (P < 0.001) and had a shorter time to thrombotic occlusion following ferric chloride injury of the carotid artery (median time to thrombosis of 8 vs. 13 min; P = 0.015). Administration of the direct-acting P2Y12 antagonist cangrelor blunted ex vivo fibrinogen binding and attenuated thrombosis (median time 20 min) in Apoe-/- mice exposed to sidestream smoke. The effects of smoke exposure required a proatherosclerotic background, as wild-type C57Bl/6 J mice exposed to smoke displayed similar fibrinogen binding and thrombotic occlusion times as did control mice.

Conclusions

Our results demonstrate that exposure to smoke heightens platelet reactivity and thrombosis in Apoe-/- mice and implicate signaling through platelet P2Y12 receptor as a mediator of the adverse consequence of smoke exposure. These results may partially explain the recent observations that smokers derive greater clinical benefit from the P2Y12 antagonist clopidogrel than do non-smokers.     

Circulating activated factor XI and active tissue factor as predictors of worse prognosis in patients following ischemic cerebrovascular events

Background

Elevated factor (F)XI is associated with an increased risk for ischemic stroke. Activated FXI (FXIa) and tissue factor (TF) have not been studied following stroke. The aim of the current study was to evaluate circulating FXIa and TF in patients with prior cerebrovascular events.

Patients/Methods

We studied 241 patients, including 162 after ischemic stroke and 79 after transient ischemic attack (TIA), recruited 6 months to 4 years (median, 36 months) after the events. Plasma TF and FXIa activity following the index event were determined in clotting assays by measuring the response to inhibitory monoclonal antibodies.

Results

Active TF was detected in 25 (10.4%) of the patients, while FXIa activity (median, 37.5 [IQR 397] pM) was found in 64 (26.7%) of the patients (p < 0.01). The prevalence of active TF and FXIa was higher in subjects with previous stroke compared with those with a history of TIA (13% vs 5.1%, p = 0.05, and 34% vs 11.4%, p < 0.0001, respectively). Patients with circulating FXIa were younger and had higher fibrinogen and interleukin-6 compared to the remainder. Patients with detectable TF or FXIa activity had higher NIHSS score, higher modified Rankin scale and lower Barthel Index than the remaining subjects (all p < 0.05).

Conclusion

Circulating active TF and FXIa can occur in patients with cerebrovascular ischemic events ≥ 6 months after the events. The presence of these factors is associated with worse functional outcomes, which highlights the role of persistent hypercoagulable state in cerebrovascular disease.     

Retinal thickness in patients with mild cognitive impairment and Alzheimer's disease

Objectives

Mild cognitive impairment (MCI) may represent a transition to early Alzheimer's disease (AD). The retinal nerve fiber layer (RNFL) is composed of axons originating in retinal ganglion cells that eventually form the optic nerves. Previous studies have shown that degenerative changes occur in optic nerve fibers and manifested as thinning of RNFL in patients with AD. The objective of this study was to assess the relationship between MCI, AD and loss of RNFL.

Patients and methods

In this study, patients fulfilling diagnostic criteria for MCI (n = 24), AD (n = 30) and cognitively normal age-matched controls (n = 24) have undergone neuro-ophthalmologic and optical coherence tomography (OCT) examinations to measure RNFL thickness.

Results

There was a significant decrease in RNFL thickness in both study groups (AD and MCI) compared to the control group, particularly in the inferior quadrants of the optic nerve head, while the superior quadrants were significantly thinner only in AD. Although AD patients may have more severe changes than MCI cases, the differences were statistically nonsignificant. Furthermore among AD patients, there was no relation to the severity of the dementia.

Conclusions

Our data confirm the retinal involvement in AD, as reflected by loss of axons in the optic nerves.     

A genetic association study of D-dimer levels with 50 K SNPs from a candidate gene chip in four ethnic groups

Introduction

D-dimer, a fibrin degradation product, is related to risk of cardiovascular disease and venous thromboembolism. Genetic determinants of D-dimer are not well characterized; notably, few data have been reported for African American (AA), Asian, and Hispanic populations.

Materials and Methods

We conducted a large-scale candidate gene association study to identify variants in genes associated with D-dimer levels in multi-ethnic populations. Four cohorts, comprising 6,848 European Americans (EAs), 2,192 AAs, 670 Asians, and 1,286 Hispanics in the National Heart, Lung, and Blood Institute Candidate Gene Association Resource consortium, were assembled. Approximately 50,000 genotyped single nucleotide polymorphisms (SNPs) in 2,000 cardiovascular disease gene loci were analyzed by linear regression, adjusting for age, sex, study site, and principal components in each cohort and ethnic group. Results across studies were combined within each ethnic group by meta-analysis.

Results

Twelve SNPs in coagulation factor V (F5) and 3 SNPs in the fibrinogen alpha chain (FGA) were significantly associated with D-dimer level in EAs with p < 2.0 × 10^− 6. The signal for the most associated SNP in F5 (rs6025, factor V Leiden) was replicated in Hispanics (p = 0.023), while that for the top functional SNP in FGA (rs6050) was replicated in AAs (p = 0.006). No additional SNPs were significantly associated with D-dimer.

Conclusions

Our study replicated previously reported associations of D-dimer with SNPs in F5 and FGA in EAs; we demonstrated replication of the association of D-dimer with FGA rs6050 in AAs and the factor V Leiden variant in Hispanics.     

Effect of pentylenetetrazole and sound stimulation induced single and repeated convulsive seizures on the MDA, GSH and NO levels, and SOD activities in rat liver and kidney tissues

Objectives

The aim of our study was to evaluate the activity of superoxide dismutase (SOD) and the levels of glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) in liver and kidney tissues in a rat model of convulsive seizure induced by single and repeated doses of pentylenetetrazole (PTZ) and sound stimulation with key ringing.

Materials and methods

Male Wistar adult rats (n = 48), were used in the experiment. The animals were divided into six groups: (1) Single Seizure Control Group (SS-Control; n = 8), (2) Repeated Seizures Control Group (RS-Control; n = 8), (3) PTZ induced Single Seizure Group (SS-PTZ Group; n = 8), (4) PTZ induced Repeated Seizures Group (RS- PTZ Group; n = 8), (5) Key-Ringing Induced Single Seizure Group (SS-KEY Group; n = 8), (6) Key-Ringing Induced Repeated Seizures Group (RS-KEY Group; n = 8). Following injections rats were observed for seizure activity for 30 min. Animals were sacrificed 24 h after induced seizure (single or last seizure) or saline administration. MDA, NO, GSH levels and SOD activities were determined in liver and kidney tissues.

Results

There was no significant difference between SS-Control and RS-Control groups, SS-PTZ and SS-KEY groups, and RS-PTZ and RS-KEY groups (p > 0.05) in none of the examined 4 parameters in liver and kidney tissues.The liver and kidney levels of MDA and NO in SS-PTZ group were found to be significantly higher than the SS-Control group (p < 0.05). In SS-KEY group, the liver and kidney levels of MDA and NO were found to be significantly higher and GSH levels were significantly lower than the SS-Control group (p < 0.05).While liver and kidney levels of MDA in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p < 0.05), liver and kidney GSH levels were significantly lower (p < 0.05). The liver levels of NO in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p < 0.05). Kidney SOD activities in RS-PTZ group and RS-KEY group were found to be significantly lower than the RS-Control group (p < 0.05).When RS-PTZ group is compared with the SS-PTZ group, the liver SOD activity and kidney NO level were found to be significantly lower in the RS-PTZ group (p < 0.05).While the liver NO level and GSH level in RS-KEY group were significantly higher than the SS-KEY group, SOD activity was significantly lower in the RS-KEY group (p < 0.05). When RS-KEY group was compared with SS-KEY group, the kidney NO level and SOD activity were found to be significantly lower in the RS-KEY group (p < 0.05).

Conclusion

In conclusion, key-ringing or PTZ induced single and repeated seizures result in increased oxidative damage and lipid peroxidation, and decreased antioxidant defense mechanisms.     

Comparison of time taken from initial presentation to histological diagnosis of Glioblastoma Multiforme (GBM) in Birmingham, United Kingdom and Strasbourg, France

Background

The aim of this study was to investigate possible delays in referral time for Glioblastoma multiforme (GBM) patients diagnosed at two similar neurosurgical centres (in Birmingham, UK and Strasbourg, France) and their impact on survival. Differences in the referral patterns for GBM patients within these healthcare systems may affect subsequent management and are potential targets to optimise the care of patients with GBM.

Methods

Medical case notes of 105 GBM patients in Birmingham and 81 in Strasbourg, admitted during October 2006 and April 2008, were reviewed. Data regarding demographic details, route of admission, presenting symptoms, date of initial presentation to a medical professional and dates of the first CT or MRI scan, first neurosurgical intervention, histological diagnosis and mortality was recorded.

Results

The median time taken from initial presentation to first neurosurgical intervention was lower in Birmingham compared to Strasbourg (13 vs. 21 days, respectively; p = 0.026). Similarly, the time taken from initial presentation to histological diagnosis was lower in Birmingham (15 vs. 24 days, respectively; p = 0.011). However, survival was poorer in Birmingham than Strasbourg (p = 0.001) and age (HR = 1.029; 95%CI 1.010-1.048; p = 0.003) and time from initial presentation to neurosurgical intervention (HR = 0.993; 95%CI 0.988-0.998; p = 0.011) were predictors of mortality in these groups.

Conclusion

Patients in Birmingham are diagnosed with GBM more rapidly than those in Strasbourg but they have poorer survival. Differences in disease severity may partially account for the observed results and further large scale work is required to support this study.     

Biomarkers of altered coagulation and fibrinolysis as measures of disease activity in active inflammatory bowel disease: a gender-stratified, cohort analysis

Background

Growing evidence recognizes inflammatory bowel disease (IBD) as a chronic inflammatory condition characterized by a hypercoagulable state and prothrombotic conditions. The aims of our study were to evaluate the abnormalities in coagulation and fibrinolysis status in patients with IBD, and to analyze parameters of altered coagulation and fibrinolysis status which can correlated with and predict inflammatory parameters of disease activity.

Methods

A cohort of 271 consecutive IBD patients was compared with healthy controls for coagulation and fibrinolysis status. Associations between altered coagulation and fibrinolysis status stratified by gender and inflammatory parameters were analyzed.

Results

The mean levels of platelet, platelet distribution width, prothrombin time, fibrinogen, activated partial thromboplastin time were significantly higher in IBD patients than in healthy controls (all P < 0.05). Mean platelet volume was lower in male patients with IBD than in healthy controls (P < 0.01). Furthermore, multiple linear regression indicated that fibrinogen was an independent predictor of ESR (β = 1.316, P = < 0.001) and CRP (β = 1.233, P = 0.015) in male patients with active ulcerative colitis. Platelet (β = 0.436, P = 0.037) and prothrombin time (β = 0.810, P = < 0.001) were predictors of Crohn's Disease Activity Index in female patients with Crohn's disease.

Conclusions

To our knowledge, this study provides characteristics on altered coagulation and fibrinolysis status in active IBD patients using the largest number of cases assembled in one study to date. Our data suggest that in IBD patients, abnormalities in coagulation and fibrinolysis status were associated with disease activity. Fibrinogen, platelet and prothrombin time were predictors of inflammation.