Antithrombotic activity of Z4A5, a new platelet glycoprotein IIb/IIIa receptor antagonist evaluated in a rabbit arteriovenous shunt thrombosis model

Introduction

The antithrombotic effect of the glycopreotein IIb/IIIa (GP IIb/IIIa) receptor antagonist Z4A5, exert alone or combination with heparin, and/or aspirin, was examined in a rabbit arteriovenous shunt thrombosis model.

Materials and Methods

Thrombosis was induced by the insertion of a silk thread (thrombogenic substrate) into an extracorporeal shunt. Before and after drug administration (0, 5, and 15 min), ex vivo adenosine diphosphate (ADP)-induced platelet aggregation and coagulation parameters (prothrombin time (PT) and activated partial thromboplastin time (APTT)) were determined in platelet-rich plasma (PRP) and platelet poor-plasma (PPP), respectively.

Results

Our data demonstrated that, compared to the control, Z4A5 decreased the thrombus weight (31-65%) in a dose-dependent manner and inhibited ADP-induced platelet aggregation (47-98%) 5 min after Z4A5 administration (25-100 mg/kg). However, PT and APTT remained stable, even at the highest dose (100 mg/kg). Heparin (100 U/kg) and aspirin (15 mg/kg) also significantly reduced thrombus mass, but this effect was accompanied by an increase of APTT by heparin. Furthermore, the combination of heparin (100 U/kg) and a low dose of Z4A5 (25 mg/kg) failed to produce an additional benefit beyond that provided by heparin or Z4A5 alone, whereas Z4A5 (25 mg/kg) plus aspirin (15 mg/kg) potentiated the antithrombotic effects of both compounds without further increasing the values of coagulation.

Conclusions

Our results indicate that Z4A5 is an effective antithrombotic agent with no significant effects on values of coagulation. Furthermore, Z4A5 can potentiate these antithrombotic effects when prescribed with aspirin.     

Effect of concentration and mode of intrathecal baclofen administration on soleus H-reflex in patients with muscle hypertonia

Objectives

Assess spinal reflex excitability after increasing intrathecal baclofen (ITB) flow by manipulation of drug concentration and mode of administration.

Methods

The effect of concentration was assessed by comparing changes in H-reflex (H/M ratio) 1–6 h after a 50 μg ITB bolus at 50 μg/ml concentration administered manually via lumbar puncture (LP, duration 1–2 min, n = 27) to a 50 μg bolus at 500 μg/ml concentration programmed through the pump and delivered via intrathecal catheter (IC, duration 10 min) above simple continuous dose (25–100 μg/day, n = 16). The effect of mode of administration was assessed by comparing peak changes in H/M ratio after 50 μg IC bolus above simple continuous dose (complex continuous mode, n = 27) to simple continuous mode only (n = 22) at equivalent daily doses (75–150 μg/day).

Results

H/M decrease was faster and overall greater after LP than IC bolus (mean 1-h 77% vs. 63%, p = 0.012; 1–6 h 91% vs. 82%, p < 0.001, respectively). H/M ratio also decreased significantly more with complex (91%) than simple continuous mode of administration (78%, p = 0.025).

Conclusions

Lower ITB concentration and complex continuous mode of administration lead to greater decrease in H/M ratio.

Significance

Decreased spinal reflex excitability after adjustment of drug and pump parameters to increase ITB flow may result in better clinical response.     

Mismatch negativity and low frequency oscillations in schizophrenia families

Objective

Theta-alpha range oscillations have been associated with MMN in healthy controls. Our previous studies showed that theta-alpha activities are highly heritable in schizophrenia patients’ families. We aimed to test the hypothesis that theta-alpha activities may contribute to MMN in schizophrenia patients and their family members.

Methods

We compared MMN and single trial oscillations during MMN in 95 patients, 75 first-degree relatives, 87 controls, and 34 community subjects with schizophrenia spectrum personality (SSP) traits.

Results

We found that (1) MMN was reduced in patients (p < 0.001) and SSP subjects (p = 0.047) but not in relatives (p = 0.42); (2) there were augmented 1–20 Hz oscillations in patients (p = 0.02 to <0.001) during standard and deviant stimuli; (3) theta-alpha (5–12 Hz) oscillations had the strongest correlation to MMN in controls and relatives (ΔR² = 21.4–23.9%, all p < 0.001), while delta (<5 Hz) showed the strongest correlation to MMN in schizophrenia and SSP trait subjects; and, (4) MMN (h² = 0.56, p = 0.002) and theta-alpha (h² = 0.55, p = 0.004) were heritable traits.

Conclusions

Low frequency oscillations have a robust relationship with MMN and the relationship appears altered by schizophrenia; and schizophrenia patients showed augmented low frequency activities during the MMN paradigm.

Significance

The results encourage investigation of low frequency oscillations to elucidate the neurophysiological pathology underlying MMN abnormalities in schizophrenia.     

Cilostazol versus aspirin therapy in patients with chronic dizziness after ischemic stroke

Background

Chronic dizziness is frequently reported by patients in the chronic stage after ischemic stroke. The aim of this study was to determine the efficacy of cilostazol versus that of aspirin for the chronic dizziness that follows ischemic stroke.

Methods

We performed a prospective, randomized, open-label, blinded endpoint trial. One hundred six patients who suffered supratentorial ischemic stroke within the previous 1–6 months and subsequently complained of persistent dizziness without other obvious sequelae were enrolled. Patients were randomly given cilostazol (200 mg/day) or aspirin (100 mg/day) for 6 months. Rates of improvement in the dizziness were then evaluated. Changes in fixation suppression of the vestibulo-ocular reflex (an indicator of cerebral control over the brainstem reflex related to balance), regional cerebral blood flow (CBF) in the cerebrum, cerebellum, and brainstem; and the Zung Self-Rating Depression Scale (SDS) were also evaluated.

Results

Dizziness was significantly improved in the cilostazol group versus the aspirin group (P < 0.0001) after the 6-month therapy. The capacity for fixation suppression of the vestibulo-ocular reflex was improved (P < 0.0001), and regional CBF in the cerebrum (relative to that in the brainstem [P = 0.003] and to that in the cerebello-brainstem [P = 0.012]) was increased only in the cilostazol group. There was no statistical difference in the change in SDS scores between the two groups.

Conclusion

Cilostazol improves the chronic dizziness that follows ischemic stroke and increases supratentorial CBF and cerebral function for adaptation of the brainstem reflex related to the sense of balance.     

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina

Application of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG.Therefore,the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions.The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0. I mg/kg or 5 mg/kg), aspirin (I mg/kg or 7 mg/kg) or LDC (0. I mg/kg clopidogrel and I mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min.CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, -48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg,-65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0. I mg/kg) plus aspirin (I mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (-70%, p<0.05 y. Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application.The effect occurs before inhibition of platelet aggregation is detectable.     

The assessment of prognostic factors in surgical treatment of low-grade gliomas: A prospective study

Objective

A prospective volumetric analysis of extent of resection (EOR) was carried out to assess surgical outcomes in adults diagnosed with hemispheric low grade gliomas (LGGs).

Materials and methods

68 consecutive patients diagnosed with LGGs were enrolled in the study. Pre- and post-operative tumor volumes and EOR were measured based on FLAIR MRI. Dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC MRI) was used for the assessment of relative cerebral blood volume (rCBV). Three outcome measures were assessed: overall survival (OS), progression-free survival (PFS), and malignant degeneration-free survival (MFS).

Results

In 6 (9%) patients permanent neurologic deficits were observed. No statistically significant dependence between the EOR and the occurrence of permanent deficits was found. The eloquent or close to the eloquent location was statistically connected with lower EOR (p = 0.023). The preoperative volume of tumors treated with gross total resection was significantly smaller than the volume of tumors in subtotal or partial resection groups (p = 0.020, p < 0.001, respectively). OS was predicted by age at diagnosis (p = 0.032), and rCBV (p = 0.002). Progression and malignant transformation occurred in 22 (32%) and 11 (16%) out of 68 patients. PFS was predicted by preoperative tumor volume (p = 0.005), postoperative tumor volume (p = 0.008), the EOR (p = 0.001), and by the rCBV (p = 0.033). MFS was predicted by preoperative tumor volume (p = 0.034), the EOR (p p = 0.020), and by rCBV (p = 0.022). Postoperative tumor volume was associated with a trend of improved MFS (p = 0.072). The univariate analysis shows the statistical trend for the relationship between histological subtype and PFS and MFS (p = 0.079, p = 0.078, respectively). Multivariate analysis selected preoperative tumor volume and rCBV as independently associated with PFS (p = 0.009, p = 0.019, respectively) and MFS (p = 0.023, p = 0.035, respectively). EOR was associated with a trend of improved PFS, and MFS (p = 0.069, p = 0.094, respectively).

Conclusions

Tumor resection of LGG with the use of intraoperative monitoring and neuronavigation is associated with a low risk of new permanent deficits, but EOR significantly decreases with the size of the tumor and/or its location in/close to the eloquent areas. Smaller preoperative tumor volume and greater EOR are significantly associated with longer OS, PFS and MFS. Preoperative rCBV is one of the important prognostic factors significantly connected with survival. Prognosis in LGGs is still under discussion. Other factors such as age, histopathological subtype and KPS should not be underestimated.     

Malignant glioma grade 3 and 4: How relevant is timing of radiotherapy?

Aims and background

The aim of this study is to determine prognostic factors that influence further outcome in patients with glioma.

Methods

Between 01/2002 and 08/2008, 153 patients with malignant gliomas of WHO-grade 3 or 4 who were treated with external beam radiotherapy with or without chemotherapy.

Results

In univariate analysis, following factors were ascertained as statistically significant prognostic parameters: grade (p = 0.000), time between operation and radiotherapy >24 days (p = 0.044) for progression-free survival; grade (p = 0.000), age < 58 years (p = 0.001), extent of surgery (p = 0.011), time between operation and radiotherapy >24 days (p = 0.009), overall treatment time >68 days (p = 0.003), use of chemotherapy (p = 0.015) for overall survival. A longer time period between resection and start of radiotherapy showed to be associated with improved outcome. After multivariate analysis, only grade (p = 0.000) remained a statistically significant factor for progression-free and grade (p = 0.000) and use of chemotherapy (p = 0.031) for overall survival.

Conclusions

We were able to recognize grade and use of chemotherapy as statistically significant prognostic determinants, but not time intervals or overall treatment time.     

Diffusion tensor and dynamic susceptibility contrast MRI in glioblastoma

Objective

We prospectively investigated the correlation between diffusion tensor (DTI), dynamic susceptibility contrast (DSC) perfusion MRI metrics and Ki-67 labelling index in glioblastomas.

Methods

We studied seventeen patients who were operated on for glioblastoma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA), relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and relative mean transit time (rMTT) ratio. In the excised tumour specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method.

Results

A significant correlation was observed between Ki-67 index and ADC ratio (r = −0.528, p = 0.029) and FA ratio (r = 0.589, p = 0.012). rCBV and rMTT presented a trend towards significant correlation with Ki-67 index (r = 0.628, p = 0.07 and r = 0.644, p = 0.06 respectively). There was a trend towards better survival for patients with gross total tumour excision and FA values lower than 0.48 (p = 0.1 and p = 0.09 respectively). No significant correlation was found between ADC ratio, rCBV, rCBF, rMTT and overall survival.

Conclusion

ADC ratio, FA ratio, rCBV and rMTT tumour/normal tissue ratios may represent indicators of glioma proliferation. FA values may hold promise for predicting survival in patients with glioblastoma.     

Single brain metastasis: resection followed by whole-brain irradiation and a boost to the metastatic site compared to whole-brain irradiation plus radiosurgery

Objective

The most appropriate treatment for a single brain metastasis is still controversial. This matched-pair analysis compared whole-brain irradiation plus radiosurgery (WBI + RS) to neurosurgical resection followed by whole-brain irradiation and a boost to the metastatic site (NR + WBI + B).

Methods

The data of 46 patients treated with WBI + RS were matched 1:1 to 46 patients treated with NR + WBI + B with respect to age, gender, Karnofsky performance score (KPS), tumor type, extracerebral metastases, and interval from first diagnosis of cancer to treatment of the metastasis, RPA class, and GPA score. Both groups were compared for local control of the treated metastasis, intracerebral control, and survival.

Results

The 1-year local control rates were 85% after WBI + RS and 78% after NR + WBI + B (p = 0.35). The 1-year intracerebral control rates were 74% and 68% (p = 0.33), respectively. The 1-year survival rates were 64% and 58% (p = 0.70), respectively. A multivariate analysis was not performed for local and intracerebral control, because no factor achieved significance on univariate analyses for these endpoints. Improved survival was associated with KPS > 70 (p = 0.032), absence of extracerebral metastases (p = 0.003), RPA-class 1 (p = 0.014), and GPA score of 3.0–4.0 (p = 0.010).

Conclusion

Treatment outcomes were not significantly different after WBI + RS or NR + WBI + B. Because WBI + RS is less invasive, it may be preferable for many patients with a single brain metastasis.     

Antithrombin and heparin cofactor II-mediated inactivation of α-thrombin by a synthetic, sulfated mannogalactan

Introduction

A mannogalactan from Pleurotus ostreatoroseus (MgPr) was chemically sulfated to give MgPr-S1, which was evaluated for its anticoagulant and antithrombotic activities, bleeding tendency, and platelet aggregation.

Materials and methods

MgPr-S1 was partially characterized by HPSEC-MALLS, methylation analysis, and ¹³C NMR spectroscopy. Its anticoagulant activity was determined by assays of aPTT, TT, α-thrombin and factor Xa residual activity, heparin cofactor II (HCII)-, or antithrombin (AT)-mediated inhibition. The antithrombotic effect was evaluated in rats using a venous thrombosis model and the bleeding tendency was also tested in vivo. Platelet aggregation was investigated by an adaptation of the method of Born [1].

Results

The hydroxyl groups of β-D-Manp units and OH-2 and OH-4 of the (1→6)-linked α-D-Galp units were preferentially substituted. The anticoagulant activity of MgPr-S1 was mainly by thrombin inhibition with antithrombin and HCII, and had an effect on platelet aggregation induced by ADP and α-thrombin. It almost completely inhibited thrombus formation in vivo at a dose of 6 mg/kg and heparin inhibited thrombus formation at a dose of 0.200 mg/kg.

Conclusions

These results suggested that the chemically sulfated mannogalactan could act as an alternative to heparin as anticoagulant.     

Terson haemorrhage in patients suffering aneurysmal subarachnoid haemorrhage: a prospective analysis of 60 consecutive patients

Objective

The concomitance of vitreous/subhyaloid haemorrhage (Terson syndrome; TS) and aneurysmal subarachnoid haemorrhage (aSAH) is commonly underestimated. The aim of this study was to determine the incidence of TS and to identify parameters that predispose its development, indicate the severity of the underlying disease, and predict outcome.

Methods

Sixty consecutive patients suffering from aSAH were included in this study. The admitting Glasgow Coma Scale scores (GCS), Hunt &; Hess (H&;H) and Fisher grades were documented. All participants were ophthalmologically examined. The outcome at discharge was estimated using the Glasgow Outcome Scale (GOS).

Results

Of the 60 patients admitted for aSAH, eleven (18.3%) displayed TS within 24 h after aneurysm rupture. Statistical analysis revealed a significant relation between TS and either high Fisher- (3.0 vs. 2.32; p = 0.008) or H&;H- (4.09 vs. 2.69; p = 0.001) and low GCS- (5.55 vs. 12.87; p < 0.001) scores. Compared with the non-TS group, patients with TS displayed generally worse outcomes (mean GOS 2.09 vs. 3.53; p = 0.007), including a significantly higher mortality (36.4 vs. 10.2%; p = 0.028).

Conclusion

Terson syndrome is likely to occur in severe aSAH with poor admission scores and indicates a worse functional outcome. An ophthalmological examination is strongly recommended in aSAH patients with poor admission scores.     

Outcome of Chlamydia pneumoniae associated acute ischemic stroke in elderly patients: a case-control study

Background

Limited data exists about the role of Chlamydia pneumoniae elderly patients with acute ischemic stroke.

Objective

To study the role of C. pneumoniae in elderly patients (age more than 65 years) with acute ischemic stroke and its impact on stroke out come.

Methods

We recruited 100 elderly patients with acute ischemic stroke and 100 age and sex matched controls over a period of 2 years. IgG and IgA anti C. pneumoniae antibodies were measured by microimmunofluorescence technique in patients and controls. Good outcome was defined as a Modified Rankin score (mRS) of ≤2.

Results

We found C. pneumoniae antibodies in 35% stroke patients and in 18% control subjects (p = 0.01). Good out come at 90 days follow up was found in 20/35(57.1%) seropositive stroke patients compared to 37/65(56.9%) seronegative stroke patients (p = 0.9).

Conclusions

C. pneumoniae antibody positivity was independently associated with ischemic stroke in elderly patients and its presence does not alter the stroke outcome.     

Facial emotion triggered cerebral potentials in treatment-resistant depression and borderline personality disorder patients of both genders

Background

Processing facial expressions of emotion is deteriorated in depression, which might be more pronounced in treatment-resistant depression (TRD), especially when the latter is comorbid with borderline personality disorder (BPD). Neurophysiologically, both early perceptual and late cognitive cerebral processes of facial emotions can be illustrated by event-related potentials (ERPs).

Methods

We therefore tried the ERPs to facial expressions of Neutral, Anger, Happiness, and Sadness in 25 patients with TRD, 15 with BPD, 22 with their comorbidity (TRD + BPD), as well as in 37 healthy volunteers. The depression levels of participants were measured with the Plutchik–van Praag Depressive Inventory (PVP).

Results

There was no group difference regarding either N1 (N170), P2, N2, P3a or P3b latency or amplitude to the four facial emotions. Reaction times (RTs) to Anger (p < .01), Happiness (p < .01), and Sadness (p < .001) in TRD, and those to Anger (p < .01) and Happiness (p < .01) in TRD + BPD patients were longer than those in the healthy volunteers. RTs to the four facial expressions were positively correlated (p < .01) with their depressive moods in all participants. In addition, PVP was positively correlated with the P2 latency to Anger in TRD + BPD patients (Fz, p < .01; Cz, p < .01; Pz, p < .01).

Conclusions

BPD contributed little to TRD or TRD + BPD regarding cerebral processing of facial emotions, however, other cognitive and behavioral data suggest a generalized impairment when responding to facial emotions in TRD and TRD + BPD patients, and a deteriorated perceptual processing of Anger in TRD + BPD patients.     

Prediction of infarct growth and neurologic deterioration in patients with positive perfusion-diffusion mismatch

Background

To assess the value of baseline clinical severity and perfusion–diffusion mismatch as predictors for further infarct growth and clinical outcome.

Methods

Patients with acute ischemic stroke and initial perfusion–diffusion mismatch within 72 h were enrolled. Baseline perfusion defects on time-to-peak (TTP) and cerebral blood volume (CBV) maps were measured. Infarct volume and stroke severity were assessed by diffusion-weighted image (DWI) and NIHSS, and were repeatedly assessed 7 days later. The predictive value of baseline NIHSS and perfusion defects on further infarct growth and neurologic deterioration was determined.

Results

Fifty-two patients (mean age 68.3 ± 12.8 years, 42% women) were enrolled. CBV defects were significantly associated with infarct growth (CBV, p = 0.02). Initial stroke severity, but not TTP and CBV mismatch (p = 0.65 and 0.76, respectively), significantly inversely correlated with neurologic deterioration (p = 0.001).

Conclusions

In patients with mismatch, those with severe symptoms initially are more likely to have infarct growth, while those with minor symptoms tend to suffer from larger extent of neurologic deterioration within 1 week. CBV is associated with further infarct growth but not clinical deterioration.     

Associations of cigarette smoking with intracranial atherosclerosis in the patients with acute ischemic stroke

Background

Although cigarette smoking has been established as an important risk factor for stroke, the effect on the atherosclerotic stenosis, which are based on observational studies, have been controversial. We set out to examine the differences in the risk factors between smokers and nonsmokers and to investigate the association of cigarette smoking with cerebral arterial stenosis.

Methods

A total of 989 consecutive patients with acute noncardioembolic ischemic stroke were prospectively enrolled from June 2004 to January 2010. The risk factor profiles were compared between smokers and nonsmokers. We analyzed the degree of stenosis in all MRA, and evaluated influencing factors in the patients with intracranial atherosclerosis (ICAS) and extracranial atherosclerosis (ECAS) who were randomly matched by age and sex.

Results

There were differences in the distribution of risk factors between the 467 (70.0%) nonsmokers and the 215 (30.0%) smokers. Nonsmokers were older (71.7 ± 11.0 versus 61.7 ± 12.0, p < 0.001) and had a higher frequency of hypertension than smokers had (75.4% versus 64.0%, p = 0.002). When smokers and nonsmokers were age- and sex-matched, smoking was more prevalent in patients with ICAS than with ECAS (32.9% versus 28.2%). Conditional regression analysis revealed that smoking and hypertension increased the odds of ICAS [smoking, odds ratio (OR): 1.83, p = 0.026; hypertension, OR: 1.84, p = 0.01], whereas hyperlipidemia increased the odds of ECAS (OR: 1.87, p = 0.034).

Conclusion

The distributions of the major risk factors for ischemic stroke were different between smokers and nonsmokers. Cigarette smoking may be more associated with ICAS than with ECAS after adjusting for potential risk factors.     

Synergistic effect of a factor Xa inhibitor, TAK-442, and antiplatelet agents on whole blood coagulation and arterial thrombosis in rats

Introduction

Activated platelets facilitate blood coagulation by providing factor V and a procoagulant surface for prothrombinase. Here, we investigated the potential synergy of a potent factor Xa/prothrombinase inhibitor, TAK-442, plus aspirin or clopidogrel in preventing arterial thrombosis and whole blood coagulation.

Methods

Thrombus formation was initiated by FeCl₃-induced rat carotid injury. Bleeding time was evaluated with the rat tail transection model. Whole blood coagulation was assessed by thromboelastographic examination (TEG) for which blood obtained from control, aspirin-, or clopidogrel-treated rats was transferred to a TEG analyzer containing, collagen or adenosine diphosphate (ADP), and TAK-442 or vehicle.

Results

TAK-442 (3 mg/kg, po), aspirin (100 mg/kg, po) or clopidogrel (3 mg/kg, po) alone had no significant effect on thrombus formation, whereas the combination of TAK-442 with aspirin and clopidogrel remarkably prolonged the time to thrombus formation without additional significant prolongation of bleeding time. TEG demonstrated that the onset of collagen-induced blood coagulation were slightly longer in aspirin-treated rats than control; however, when the blood from aspirin-treated rats was subsequently treated in vitro with 100 nM TAK-442, the onset of clotting was significantly prolonged. In contrast, only marginal prolongation was observed with TAK-442 treatment of blood from control animals. The onset time of ADP-induced blood coagulation was slightly longer in clopidogrel-treated rats compared with control, and it was further extended by TAK-442 treatment.

Conclusion

These results demonstrate that blood coagulation can be markedly delayed by the addition of TAK-442 to antiplatelets treatment which could contribute to synergistic antithrombotic efficacy in these settings.     

Evaluation of the platelet count drop method for assessment of platelet function in comparison with “gold standard” light transmission aggregometry

Introduction

Hyporesponsiveness to antiplatelet agents has been linked to an increased risk of major adverse cardiovascular events. However, light transmission aggregometry (LTA), the gold standard methodology for assessing platelet function, requires expertise and is labour-intensive, which render its use in clinical settings impractical. We assessed whether platelet count drop (PCD), a technique widely available in any haematology laboratory, could replace LTA in testing for inhibition of platelet aggregation induced by antiplatelet agents.

Materials and methods

One hundred and sixty-one coronary artery disease patients taking aspirin alone and 91 patients taking a combination of aspirin and clopidogrel were enrolled. Platelet aggregation was measured by LTA and PCD stimulated with 1.6 mM of arachidonic acid (AA) for aspirin and 5 and 20 μM of adenosine diphosphate (ADP) for clopidogrel.

Results

Correlation between AA-induced LTA and PCD was inexistent (r = - 0.043, p = 0.587), while correlation between ADP-induced LTA and PCD was low (r = 0.374, p < 0.0001 for ADP 5 μM and r = 0.402, p < 0001 for ADP 20 μM). PCD, whether stimulated with AA or ADP, overestimated platelet aggregation as assessed by LTA, by 13-18%. The wide 95% limits of agreement suggest that the assays can disagree significantly in individual patients.

Conclusions

Although the PCD method is widely available in non-specialized laboratories, our results demonstrate that there is poor correlation with the current gold standard, i.e. LTA. Thus, PCD should not be used in replacement of LTA to assess antiplatelet responsiveness.     

Postoperative changes in the superficial temporal artery and the external carotid artery duplex sonography after extra-intracranial bypass surgery in European Moyamoya disease

Introduction

Despite Duplex ultrasonography being a noninvasive, easily repeatable, readily available and economical tool, this examination and its normal ranges are rarely described in Moyamoya disease (MMD).

Methods

Duplex ultrasonography examinations of the superficial temporal artery (STA) and external carotid artery (ECA) were performed preoperatively, postoperatively (within 30 days) and as follow-up exams (6 months postoperatively) after 32 cerebral revascularization procedures in 20 European patients with MMD.

Results

A significant higher mean diastolic flow of STA compared to preoperative values was found in postoperative (p < .000) and follow-up exams (p < .001) in Duplex ultrasonography. Postoperative and follow-up Duplex sonography of STA also showed a significantly higher mean systolic flow compared to preoperative values (p < .05 and p < .05). Also ECA showed significantly changes after bypass surgery (p < .05).

Conclusion

Duplex ultrasonography of STA is a reliable and non-invasive tool to investigate hemodynamic changes after bypass surgery and to detect bypass patency in European patients with MMD.     

Predictors of short-term outcomes following endoscopic pituitary surgery

Objective

Refinement of endoscopic pituitary surgery requires an understanding of the impact of demographic and surgical variables on outcomes.

Methods

Multivariate logistic regression and ANOVA models were used to explore variables for association with outcomes in a consecutive series of 57 patients undergoing endoscopic pituitary surgery.

Results

The mean duration of surgery was 177 min and was longer in patients with larger tumor size (p = 0.03) and presentation with visual symptoms (p = 0.02) in univariate analyses. The median duration of hospitalization was 3 days and was longer in patients with larger tumors (p = 0.0005). Gross tumor removal was achieved in 89%. Tumor size correlated with extent of tumor removal with an almost 3-fold decrease in complete tumor removal for every 1 cm increase in tumor size (p = 0.047). High rates of hormonal control (90%) and improvement in visual symptoms (92%) were noted.

Conclusions

High rates of gross tumor removal, hormonal cure and visual field improvement were noted in this series. Markers including tumor size and visual symptoms may be used to stratify patients.     

Bandpass filter settings differentially affect measurement of P50 sensory gating in children and adults

Objective

This study investigated the effect of four different bandpass filter settings on measures of the P50 component and the signal-to-noise ratios (SNR) of averaged ERPs obtained from a sensory gating paradigm employing paired-click stimuli.

Methods

Participants were adults (n = 18) 20–55 years old and children (n = 25) 5–10 years old who were free of neurological disorders.

Results

Results show that the filter settings (0.23–75 Hz, 10–50 Hz, 10–75 Hz, and 10–200 Hz) differentially affected the P50 amplitude, noise power and SNR measures of the conditioning and test clicks, and P50 T/C ratios.

Conclusions

The 10–50 Hz filter setting may be optimal in studies that include only adults as these settings resulted in the smallest mean P50 T/C ratio, a reasonable standard deviation (SD) for the ratio, and the highest SNRs. The 10–200 Hz filter may be the best for studying young children as this setting had the smallest mean and SD of P50 T/C ratios for these participants.

Significance

In studies that include both adults and children investigators are advised to use the 10–200 Hz filter setting because the smaller variability of sensory gating in the child group helps ensure better homogeneity of variance measures between the groups.