Correlation of glioma proliferation assessed by flow cytometry with Tc-Tetrofosmin SPECT uptake

Objectives

Brain single-photon emission computed tomography (SPECT) has been proposed as a potentially useful modality for the metabolic assessment of various brain tumors.

Material and methods

In a 10-patient prospective pilot study we evaluated whether ^99mTc-Tetrofosmin (^99mTc-TF) uptake correlates with glioma proliferative activity assessed by flow cytometric analysis. ^99mTc-TF brain SPECT was performed shortly before surgical tumor excision.

Results

Eight patients were diagnosed with glioblastoma multiform and 2 with anaplastic astrocytoma. All tumors were aneuploid. We found a significant positive linear correlation between ^99mTc-TF uptake and percentage of tumor cells on the S-phase of the cell cycle (r = 0.92, P = 0.001).

Conclusion

Initial evidence suggests that ^99mTc-TF could provide a non-invasive indicator of glioma proliferative activity.     

Early superficial temporal artery to middle cerebral artery bypass in acute ischemic stroke

Objective

To evaluate the effects and safety of superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis in the early stage after an acute ischemic event and the improvement of present symptoms in patients with intracranial atherosclerotic occlusive disease with stroke/stroke in progress.

Methods

From 2006 to 2010, 20 patients (15 males and five females) with atherosclerotic cerebrovascular disease were treated with an STA–MCA bypass. All of the patients presented with an acute ischemic stroke or stroke in progress despite maximal medical treatment. The patients underwent an STA–MCA bypass within 7 days from symptom onset. The clinical outcome and hemodynamic study of the 20 patients were preoperatively and postoperatively investigated. A pooled analysis was performed, and the results were compared with those obtained from other delayed STA–MCA bypass studies.

Results

Among the 20 patients who underwent an early STA–MCA bypass, fourteen (70%) patients achieved a good functional outcome (mRS 0, n = 3; mRS 1, n = 9; mRS 2, n = 2). Prior to surgery, the mean basal regional cerebral blood flow (rCBF) and cerebrovascular reserve capacity (CVR) in the symptomatic hemisphere were 37.3 ± 4.3 ml/100 g/min and −1.68 ± 2.9%. The mean basal rCBF and CVR had significantly increased postoperatively, and no reperfusion-induced hemorrhage had occurred. In the pooled analysis, no significant differences were observed in the clinical outcome (P = 0.328) or in the incidence of postoperative complications (P = 0.516) between patients who underwent an early STA–MCA bypass and in patients who underwent a delayed STA–MCA bypass in previous studies.

Conclusions

In this study, which consisted of 20 carefully selected patients with acute ischemic stroke, an early STA–MCA bypass was safely and effectively performed, and in some cases, an early STA–MCA bypass resulted in rapid neurological improvement. An early STA–MCA bypass was beneficial in select patients who had acute ischemic stroke with imaging evidence of a small infarction.     

Substantia nigra echogenicity is correlated with nigrostriatal impairment in Machado-Joseph disease

BackgroundSeveral studies have demonstrated increased substantia nigra (SN) echogenicity in Parkinson's disease (PD) and Machado-Joseph disease (MJD). Pathological substrate of PD is characterized by dopaminergic nigrostriatal cell loss, also found in MJD. Also, SN hyperechogenicity might be associated with nigrostriatal dysfunction in PD, when comparing dopamine transporter binding with SN echogenicity. The present study aimed to correlate the SN echogenic size and striatal dopamine transporter density in MJD patients.MethodsWe performed TCS in 30 subjects and SPECT with [^99mTc]-TRODAT-1 in 18 subjects with MJD. Fifteen healthy subjects matched for age and gender formed a control group. TCS and [^99mTc]-TRODAT-1 SPECT findings from both MJD patients and control subjects were compared.ResultsThere were no differences regarding age (p = 0.358) or gender (p = 0.566) between groups (MJD versus control group). Mean DAT binding potentials and SN echogenicity were significantly different between groups. There was a significant negative correlation with regard to the SN echogenic size and the ipsilateral striatal TRODAT-1 uptake: the higher the SN echogenicity, the lower the DAT uptake in the ipsilateral cerebral hemisphere.ConclusionIncrease in SN echogenic size likely correlates with presynaptic dopaminergic nigrostriatal dysfunction in MJD, suggesting a concurrent in vivo pathophysiological mechanism.     

Perioperative complications of superficial temporal artery to middle cerebral artery bypass for the treatment of complex middle cerebral artery aneurysms

Object

Only a few studies have reported the risk of ischemic complications occurring when superficial temporal artery (STA) to middle cerebral artery (MCA) anastomosis is performed during surgery for complex MCA aneurysms.

Subjects and methods

This is a retrospective study of 10 patients (age 52–73) with MCA aneurysms treated with revascularization surgery. The aneurysms were 10–50 mm in size (mean: 21 mm). We studied the causes and frequency of ischemic complications by analyzing postoperative magnetic resonance imaging.

Results

Postoperative diffusion-imaging confirmed ischemic complications in six of the 10 patients (in two of the five ruptured aneurysms and in four of the five unruptured). The ischemic complications that observed were infarction of the lenticulostriate artery territory in three cases, cortical infarction in two cases, and cerebral infarction that was likely to be due to cerebral vasospasm in one case. In one case, both cortical infarction and infarction of the lenticulostriate artery territory were observed. The Glasgow Outcome Scale (GOS) scores at the time of discharge indicated good recovery (GR) and moderate disability (MD) in seven cases, severe disability (SD) in two cases, and death (D) in one case.

Conclusions

The present study suggests the possibility that STA–MCA anastamosis in surgeries for MCA aneurysms can be performed with comparatively better safety. However, the temporary occlusion time with this surgery is longer than that with a temporary clipping for aneurysmal surgery; thus, we believe that adequate countermeasures are required to prevent ischemic complications.     

Evaluation of FDG-PET and ECD-SPECT in patients with subcortical band heterotopia

Objective: The purpose of this retrospective study was to clarify the cellular activities of ectopic neurons in subcortical bands and to evaluate the imaging features of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and ^99mTc ethyl cysteinate dimer (ECD) single-photon emission computed tomography (SPECT) in a series of patients with subcortical band heterotopia (SBH). Materials and methods: The cases of 12 patients with SBH (3 men and 9 women; age range, 2–51 years) were evaluated on the basis of their MRI findings. Eight ¹⁸F-FDG PET and 12 ^99mTc-ECD SPECT images were obtained. The uptakes of these images were compared with electroencephalography (EEG) or MRI findings such as band thickness. In all patients, easy Z-score Imaging System (eZIS) software was used to statistically analyze the SPECT images. Results: Of the eight ¹⁸F-FDG PET images, five showed higher uptake in the thick subcortical bands than in the overlying cortex. Of the 12 ^99mTc-ECD SPECT examinations with eZIS images, nine indicated increased regional cerebral blood flow (rCBF) areas corresponding to the band locations. Of the eight ¹⁸F-FDG PET examination findings, six were congruent with the rCBF distributions on the eZIS images. Eight of the 12 patients showed correspondence to the increased rCBF on the eZIS images, the band locations on MRI, and abnormal discharge sites on EEG. Conclusions: Ectopic neurons in subcortical bands may have higher glucose metabolism and/or increased rCBF compared to the overlying cortex. ¹⁸F-FDG PET and ^99mTc-ECD SPECT using eZIS can be helpful to clearly detect the cellular activities of ectopic neurons in patients with SBH.     

Analysis of ischemic cerebral lesions using 3.0-T diffusion-weighted imaging and magnetic resonance angiography after revascularization surgery for ischemic disease

Background

Cerebral revascularization surgery (CRS) is increasingly recognized as an important component in the treatment of complex cerebral vascular disease and tumors. CRS requires that the incidence of perioperative neurological complications should be minimized, because CRS for ischemic disease is often not the goal of treatment, but rather a prophylactic surgery. CRS carries the risk of focal postoperative neurological deficits. Little has been established concerning mechanisms of post-CRS ischemia. We used 3.0-T diffusion-weighted magnetic resonance imaging (DWI) and magnetic resonance angiography (MRA) to analyze the incidence and mechanism of ischemic lesions.

Methods

We studied the anterior circulation territory after 20 CRS procedures involving 33 vascular anastomosis procedures (13 double anastomoses and 7 single anastomoses) in 12 men and 8 women between June 2007 and October 2011. The operations included single or double superficial temporal artery–middle cerebral artery (STA–MCA) anastomosis to treat internal carotid artery/MCA occlusions or severe MCA stenosis. A combined STA–MCA anastomosis and indirect bypass were performed for moyamoya disease. Postoperative DWI and MRA were obtained in all patients between 24 and 96 h after surgery to detect thromboembolism, hypoperfusion, or procedural ischemic complications and vasospasms of the donor STA.

Results

Follow-up DWI and MRA were carried out 1.8 ± 0.6 days after CRS (range, 1–4 days). Temporary occlusion time for anastomoses averaged 18.9 min (range, 16–32 min). Asymptomatic new hyperintensities occurred in the ipsilateral hemisphere of 2 patients on postoperative DWI (10% patients/6.0% anastomoses), and 1 moyamoya patient (5.0% patients/3.0% anastomoses) developed a symptomatic hyperintensity in the ipsilateral occipital lobe in response to the operation. Two abnormal small (<5 mm) cortical DWI lesions were caused by sacrifices of a small branch of the recipient MCA.

Conclusion

This study is the first postoperative 3.0-T DWI study of CRS and related clinical events. The incidence of symptomatic postoperative DWI abnormalities was restricted to 1 moyamoya patient representing 5.0% of total patients and 3.0% anastomoses. Although some postoperative DWI abnormalities occurred, CRS was found to be safe with a low risk of symptomatic ischemia.     

Haemostatic effects of phytoestrogen genistein in postmenopausal women

Introduction

Genistein is an isoflavone phytoestrogen derived from the soybean which acts as natural selective estrogen receptor modulator. Various studies have pointed out its cardioprotective role. The aim of the study was to evaluate the haemostatic effects of genistein in postmenopausal women.

Material and methods

In this double-blind placebo-controlled trial we enrolled 104 healthy postmenopausal women with osteopenia. 53 patients (mean age 54.9 ± 4.2 yr; BMI 23.4 ± 3.2 Kg/m²) received genistein (54 mg/day) and 51 patients (mean age 55.4 ± 4.3 yr; BMI 23.6 ± 3.6 Kg/m²) received an identical placebo-tablet. Both groups received a calcium and vitamin D supplement. Plasma levels of D-dimer (DD), plasminogen activator inhibitor-1 (PAI-1) and prothrombin fragment 1 + 2 (F1 + 2) were measured at baseline and after 6 and 12 months of treatment.

Results

Baseline characteristics of the two groups were similar. Compared with placebo, genistein decreased significantly DD (p < 0.001), but did not affect PAI-1 and F 1 + 2 plasma levels.

Conclusion

The results of our study do not confirm effects of genistein on activation of the haemostatic system, but on the contrary the significant decrease of DD could indicate a possible cardioprotective role of genistein in postmenopausal women.     

Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients

Introduction

In clinical trials, fixed-dose enoxaparin (40 mg once daily) reduces the risk of venous thromboembolism (VTE) in medically-ill patients. However, morbidly obese patients were under-represented in these trials and using fixed-dose enoxaparin in obese patients may be inadequate. We completed a pharmacokinetic study in morbidly obese, medically-ill patients to determine if weight-based dosing of enoxaparin for VTE prophylaxis was feasible, without excessive levels of anticoagulation, as determined by peak anti-Xa levels.

Materials and Methods

Twenty eight morbidly obese (BMI ≥ 35 kg/m²) patients were enrolled and completed the study protocol. Enoxaparin 0.5 mg/kg was administered once daily subcutaneously and peak anti-Xa levels were measured approximately 4-6 hours after the enoxaparin dose.

Results and Conclusions

Overall, 46% of patients were female, the average age (± SD) was 54 (± 11) years, and the average weight and BMI were 135.6 kg (± 25.3) and 48.1 kg/m² (± 11.1), respectively. The average daily dose of enoxaparin was 67 mg (± 12). The average peak anti-Xa level was 0.25 (SD ± 0.11, range 0.08 to 0.59) units/mL. Peak anti-Xa levels did not significantly correlate with weight or BMI. There were no bleeding events, symptomatic VTE, or significant thrombocytopenia.In morbidly obese, medically-ill patients, use of weight-based enoxaparin dosed at 0.5 mg/kg once daily is feasible and results in peak anti-Xa levels within or near recommended range for thromboprophylaxis, without any evidence of excessive anti-Xa activity. These data suggest that this weight-based regimen may be more effective than standard fixed-dose enoxaparin. Clinical outcome studies are warranted to determine the clinical safety and efficacy of this regimen.     

Evaluation of cerebral vasomotor reactivity in Parkinson's disease: is there any association with orthostatic hypotension?

Objective

Our aim was to look for a probable relationship between cerebral vasomotor reactivity (VMR) and orthostatic hypotension (OH) in Parkinson's disease (PD).

Materials and methods

This study was conducted on 44 patients with PD. Assessment of cerebral VMR was performed by means of transcranial Doppler (TCD) of middle cerebral artery (MCA) before and after a vasodilatory stimulus, carbon dioxide test. Moreover, orthostatic hypotension was evaluated.

Results

OH was presented in 12 (27.3%) Parkinson's patients. The average resting blood flow velocity (BFV) in the MCA was 30.20 (SD = 9.58) cm s⁻¹ which significantly increased to 46.25 (SD = 16.23) cm s⁻¹ after carbon dioxide test (P < 0.001). Impaired VMR was observed in 15 (34.1%) of the subjects, while it was not associated with the presence of OH (P = 0.770).

Conclusion

Evaluation of VMR in patients affected by PD, could assist in early diagnosis of cerebral autonomic dysfunction and prevent its serious consequences prior and more valid to OH.     

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.     

A circadian clock in murine bone marrow-derived mast cells modulates IgE-dependent activation in vitro

Circadian rhythm is expressed in most organisms, and many functions and parameters in the immune system are associated with time-of-day. However, it is largely unknown if local circadian clocks in immune cells directly control physiological outcomes. We hypothesized that a circadian clock in murine bone marrow derived mast cells (BMMCs) modulates IgE-dependent activation in vitro. Mature BMMCs, grown from bone marrow of C57BL/6 mice, were synchronized with serum rich media (50% horse serum). Total RNA was harvested from BMMCs at 4 h intervals for up to 72 h following synchronization and expression of circadian genes (mPer1, mPer2, Bmal1, Rev-erbα, and Dbp) was measured by quantitative PCR. Serum shock synchronized expression of circadian genes (mPer2, Bmal1, Rev-erbα, and Dbp) in BMMCs. Synchronized BMMCs stimulated via the high affinity IgE receptor (FcεRI) at different time intervals display circadian rhythms in IL-13 and IL-6 mRNA expression. The expression of fcer1a gene and FcεRIα protein displayed a circadian pattern following serum shock, with mean periods of 18.9 and 28.6 h, respectively. These results demonstrate that synchronized BMMCs provide an in vitro model to study circadian mechanism(s) associated with allergic disease and that circadian oscillation of cytokine production following IgE-dependent activation is at least in part due to circadian oscillation of FcεRIα.     

Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications

Introduction

Coronary artery thrombosis in ST-elevation myocardial infarction (STEMI) is a dynamic process often preceded by episodes of silent plaque rupture and subocclusive thrombosis. Thrombus organization is achieved by ingrowth of endothelial and smooth muscle cells. Clinical significance and impact of thrombus neovascularization on primary percutaneous coronary intervention (pPCI) outcome remain unclear. Therefore we investigated composition and neovascularization of thrombi aspirated during pPCI and their association with clinical and angiographic parameters of STEMI patients.

Methods

Aspirated thrombi retrieved from 84 STEMI patients were classified as fresh (< 1 day), lytic (1-5 days) or organized (> 5 days). Thrombus neovascularization was evaluated immunohistochemically using CD34, CD31 and VEGF antibodies. CD34 and CD31 immunopositive (CD34/CD31 +) cells were organized as single, clusters and microvessels. VEGF positivity was graded as low or high, based on thrombus surface immunopositive area.

Results

CD34/CD31 + cells were present in 67% of all aspirated thrombi. Thrombus CD34/CD31 positivity was associated with previous history of angina pectoris (χ² = 6.142, p = 0.013) and lower myocardial blush grade (MBG < 3, χ² = 12.602, p < 0.001). Organization of CD34/CD31 + cells showed inverse association with the extent of VEGF positivity (χ² = 10.607, p = 0.005). Fresh thrombi were associated with shorter ischemic time (U = 237.5, p = 0.002) and MBG 3 (χ² = 6.379, p = 0.012).

Conclusions

Older thrombus age and neovascularization are associated with suboptimal myocardial perfusion in STEMI patients. Thrombus VEGF expression is inversely associated with degree of CD34 + cell organization. Therefore, neovascularization of aspirated thrombi may indicate the duration of thrombosis, coronary microcirculation status and outcome in STEMI 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.     

Lassen's equation is a good approximation of permeability-surface model: new α values for 99mTc-HMPAO and 99mTc-ECD

Brain perfusion tracers like [^99mTc] d,l-hexamethyl-propyeneamine oxime (^99mTc-HMPAO) and [^99mTc] ethyl-cysteinate dimer (^99mTc-ECD) underestimate regional cerebral blood flow (rCBF) at high flow values. To improve linearity between tracer accumulation and rCBF, two different models have been proposed. One is Lassen''s correction algorithm for back-diffusion of tracer, and the other is based on the permeability-surface (PS) model for correction of low first-pass extraction. Although both these models have the same goal, they have completely different forms of equation. It was demonstrated that mathematical approximation of the PS model equation leads to Lassen''s equation. In this process, the relationship between PS, CBF values and Lassen''s parameter was acquired, and how to correct both the back-diffusion and low first-pass extraction was also demonstrated. A computer simulation confirmed that the two models provided similar consequences when the parameter value is chosen according to the relationship found. Lassen''s equation can be used to correct not only back-diffusion but also low first-pass extraction. To perform overall correction, the parameter value we have been using for decades may be too weak. I estimated that the parameter value for overall correction of HMPAO would be around 0.5, and that of ECD would be around 0.65.     

Neuropsychological tests and [99mTc]-HM PAO SPECT in the diagnosis of Alzheimer's dementia

Twenty-three patients with Alzheimer's dementia (AD) in relatively early stages and 40 patients with other cognitive disorders of vascular or degenerative aetiology underwent neuropsychological examination and [^99mTc]-HM PAO single photon emission computed tomography (SPECT). In contrast to the commonly accepted notion of a posterior temporoparietal reduction of tracer uptake as the typical SPECT pattern of AD, the most consistent feature found in the SPECT images of our AD patients was a hippocampal uptake deficit, associated with a variable degree of temporal, parietal and frontal deficit (extending from the posterior to the anterior regions), according to the severity of the disease. These results support the theory of AD as a hippocampal dementia, at least in the early stages. Neuropsychological tests were found to be somewhat more specific and more accurate than SPECT in distinguishing AD from non-AD cases.     

A potential thrombus diagnosis reagent based on P-selectin monoclonal antibody SZ-51 light chain

Introduction

P-selectin is a well characterized platelet adhesion molecule that can shift from the secretory granules to the surface of activated platelets, which makes it a potential target in thrombus diagnosis and therapy. SZ-51 is a monoclonal antibody against P-selectin.

Materials and methods

To build a potential thrombus diagnosis reagent, we expressed the light chain of SZ-51 (SZ-LC) in P. pastoris and the protein was highly purified by the procedure combining nickel affinity purification, Q-column and Superdex 75 column chromatography. The purified recombinant SZ-LC was labeled with ^99mTc and used for blood clearance, in vitro platelet binding and dog thrombus binding assay.

Results and conclusion

The yield of SZ-LC by the expression and purification method reached above 70 mg/L culture. We found that the nucleotide from ^99mTc-SZ-LC was removed quickly through animal kidney, and ^99mTc-SZ-LC could bind specifically to the activated human platelet in vitro. More importantly, with this recombinant protein, we successfully detected the fresh thrombus that was induced in dog vein. These results suggested that the recombinant SZ-LC expressed by P. pastoris was functional active and a potential reagent for thrombus diagnosis.     

Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex

The purpose of the present study was to assess the effects of vagus nerve stimulation (VNS) therapy on regional cerebral blood flow (rCBF) in depressed patients. Regional cerebral blood flow (rCBF) was assessed by [^99mTc]-HMPAO-single photon emission computed tomography (SPECT) before and after 10 weeks of VNS in patients participating in an open, uncontrolled European multi-center study investigating efficacy and safety of VNS. Patients suffered from major depression, with a baseline score of ≥ 20 on the 24-item Hamilton Depression Rating Scale (HDRS) and had been unsuccessfully treated with at least two adequately prescribed antidepressant drugs. Data of 15 patients could be analyzed using SPM 2. After 10 weeks of VNS (20 Hz, 500 μs pulse width, stimulation during 30 s every 5 min at the maximal comfortable level) rCBF was increased in the left dorsolateral/ventrolateral prefrontal cortex (Brodmann areas 46 and 47) and decreased in the right posterior cingulate area, the lingual gyrus and the left insula. Our findings are in line with earlier results which showed that VNS increases rCBF in the left dorsolateral prefrontal cortex. The modulation of the activity in this region could be associated with the antidepressant efficacy of VNS.     

Single photon emission computed tomography with99mTc HM-PAO in the study of focal epilepsy

We used^99mTc HM-PAO SPECT to study 50 patients with partial epilepsy: 47 interically and 3 during a seizure. All 3 patients studied during a seizure presented an area of increased tracer uptake. Of those in whom recordings were taken during seizure-free intervals 35 (74%) showed perfusion asymmetries: 27 (57%) with decreased and 8 (17%) with increased uptake. We discuss the findings and compare them with those of similar studies using SPECT and positron emission tomography.

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Sommario Sono stati studiati mediante SPECT con^99mTc HM-PAO 50 pazienti affetti da epilessia parziale, 47 in fase intercritica e 3 durante la crisi. Tutti i pazienti registrati in fase critica hanno dimostrato un focolaio di iperfissazione del tracciante. Tra quelli registrati in fase intercritica 35 (74%) hanno evidenziato asimmetrie di perfusione di cui 27 (57%) ipofissanti ed 8 (17%) iperfissanti. I risultati sono discussi e confrontati con quelli di analoghi lavori condotti mediante tomoscintigrafia e tomografia a positroni.

     

Neuroprotective effect of the novel glutamate AMPA receptor antagonist YM872 assessed with in vivo MR imaging of rat MCA occlusion

The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was evaluated by using MR imaging and histopathology of rats subjected to permanent MCA occlusion. Two treatment groups with continuous i.v. infusion of 20 mg kg⁻¹ h⁻¹ YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n=9) and 24 h YM872 treatment group (n=8) respectively, were compared to a control group (n=8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of the ischemic tissue damage was studied by diffusion weighted MR imaging and 24 h after MCA occlusion. The volume of ischemic tissue damage as assessed by diffusion weighted MR imaging h after MCA occlusion was significantly smaller in both YM872 treatment groups (99±52 mm³ and 102±44 mm³ compared to 186±72 mm³ in the control group, ±S.D. and p=0.008). The infarct volume as assessed by T2 weighted MR imaging 24 h after MCA occlusion was significantly smaller only in the 24 h YM872 treatment group (262±57 mm³ compared to 366±49 mm³ in the control group, ±S.D. and p=0.01) while the infarct volume in the 4 h YM872 treatment group (357±88 mm³) was similar to the control group. YM872 treatment significantly reduced the infarct volume 24 h after MCA occlusion when the drug was administered as continuous infusion during the 24-h observation period.     

Endothelial, platelet, and tissue factor-bearing microparticles in cancer patients with and without venous thromboembolism

Background

Cancer is a prothrombotic state, with an increased prevalence of venous thromboembolism (VTE). Microparticles (MPs) are sub-micron-sized vesicles derived from activated or apoptotic cells that may play a role in VTE, although evidence of this association is still limited.

Objectives

To evaluate the hypothesis that elevated numbers of endothelial (EMPs), platelets (PMPs), and Tissue Factor-bearing MPs (TF⁺MPs) in plasma may contribute to cancer-associated thrombosis.

Patients/Methods

EMPs, PMPs and TF⁺MPs plasma levels were measured in 90 consecutive patients (cases) referred to our Department (30 with a first episode of unprovoked VTE; 30 with active cancer; 30 with a diagnosis of acute VTE associated with active cancer), and in a group of 90 healthy subjects (controls). MPs analyses were performed by flow-cytometry (Cytomics FC500).

Results

Cases showed statistically significant higher (mean ± SD) circulating EMPs and PMPs plasma levels (920 ± 341 and 1221 ± 413 MP/μL, respectively) than controls (299 ± 102 and 495 ± 241 MP/μL; p < 0.005). Moreover cancer patients (with and without VTE) showed higher (mean ± SD) TF⁺MPs (927 ± 415 MPs/μL) than controls (204 ± 112 MPs/μL; p < 0.001). The subgroup of cancer patients plus VTE showed statistically significant higher TF⁺MPs plasma levels (1019 ± 656 MPs/μL) than cancer patients without VTE (755 ± 391 MPs/μL, p = 0.002). Multivariate analysis failed to show a significant association between elevated TF⁺MPs and VTE in cancer patients.

Conclusions

Our results suggest that MPs might be an important intermediate in the cascade of cellular injury and vascular dysfunctions underlying the process of thrombosis, particularly in cancer. Further clinical investigations are needed to confirm the precise role of MPs in predicting hypercoagulable state in patients with cancer.