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OBJECTIVE: To determine the prevalence of the Torque teno virus in healthy donors in the northern and northwestern regions of the state of Paraná, southern Brazil.METHODS: The Torque teno virus was detected by a nested polymerase chain reaction using a set of oligoprimers for the N22 region.RESULTS: The prevalence of the virus was 69% in 551 healthy blood donors in southern Brazil. There was no statistically significant difference between the presence of the virus and the variables gender, ethnicity and marital status. There was significant difference in the prevalence of the virus regarding the age of the donors (p-value = 0.024) with a higher incidence (74.7%) in 18- to 24-year-old donors.CONCLUSION: A high prevalence of Torque teno virus was observed in the population studied. Further studies are needed to elucidate the routes of contamination and the clinical implications of the virus in the healthy population.

Background Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates. Methods The frequencies of the HLA-A, HLA-B, and HLA-DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Parana State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or “pardos”] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology. Results In the analysis of the total samples, 20 HLA-A, 32 HLA-B, and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA-A*02 (25.4%), HLA-B*44 (10.9%), and HLA-DRB1*13 (13.9%). The most frequent haplotypes were HLA-A*01-B*08-DRB1*03 (2.3%), A*02-B*44-DRB1*07 (1.2%), and A*03-B*07-DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA-A*68, B*08, and B*58 allele frequencies among ethnic groups. Conclusions This study provides the first data on the HLA-A, HLA-B, and HLA-DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil.

Background The criterion (gold) standard to detect anti-human leukocyte antigen (HLA) antibodies is the complement-dependent cytotoxicity (CDC) assay. Recently, more sensitive methods have been used for the same purpose. Methods This study analyzed 70 serum samples of patients with end-stage renal disease using CDC, CDC with the addition of anti-human globulin (CDC-AHG), CDC with the addition of dithiothreitol (CDC-DTT), and the recent solid-phase immunoassay (SPI; Labscreen PRA) to detect anti-HLA antibodies. Results Mean percent panel reactive antibodies (PRA) detected by SPI was 37.5% (±34.2) higher than the values detected by the other methods. Comparative analyses revealed significant difference between CDC and CDC-AHG, and between CDC and SPI (P < 0.0001), but not between CDC-AHG and SPI (P = 0.8026). Conclusion Although the CDC-AHG method is “old,” its performance to detect anti-HLA antibodies in the samples analyzed was comparable to the SPI in the evaluation of percent class I PRA.

The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

Retrograde flow through the anterior spinal artery (ASA) from the cervical vertebral artery (VA) to the intracranial distal VA due to disrupted perfusion caused by bilateral VA occlusion is rare. We report two cases of hemodynamic vertebrobasilar circulatory insufficiency caused by bilateral VA occlusion. In these patients, the ASA filled in the retrograde direction, and provided collateral support to the ipsilateral posterior inferior cerebellar artery. The patients were treated with drip intravenous infusion of edaravone and/or argatroban. One patient had a good collateral supply from the posterior communicating artery and recovered almost completely within one month, but the other did not and lapsed into a coma, with generalized hyperreflexia, pin-point pupils, and ataxic respiration. Severe calcified lesions on three-dimensional computed tomography angiography at the occlusion site in the second patient indicated direct surgery including right superficial temporal artery to superior cerebellar artery anastomosis, rather than the endovascular approach. Retrograde flow through the ASA may be observed in this type of critical situation, and may be an important source of collateral supply to the posterior fossa territory.

The precise etiology of perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH) has not yet been determined. We decided to compare the venograms of patients with P-SAH with those of patients with aneurysmal SAH (A-SAH) to examine the relationship between P-SAH and venous drainage patterns.We retrospectively studied 18 patients with P-SAH during the past 10 years and 112 patients with ruptured A-SAH during the past 4 years by reevaluating their venograms for possible abnormalities in venous structures, particularly focusing on the basal vein of Rosenthal (BVR). Anatomical variants were classified into three types according to the drainage pathway.The location and drainage pathway of the BVR proved to be a significantly more primitive configuration in patients with P-SAH than in those with A-SAH (P0.05). On the other hand, physical action including components of the Valsalva maneuver were the cause of nine cases of P-SAH (69.2%) in this case profile. The occurrence rate was significantly higher in the P-SAH group than in the A-SAH group (14.3%) (p0.05).Our data suggest that failure of longitudinal anastomoses between the primary primitive veins as well as excessive strenuous exertion including components of the Valsalva maneuver plays an important predisposing role in the etiology of P-SAH.

The effect of cisternal drainage and intrathecal urokinase (UK) injections in preventing symptomatic vasospasm after aneurysmal subarachnoid haemorrhage was retrospectively studied in 69 patients with uniform backgrounds with regard to subarachnoid haemorrhage (SAH; WFNS grade I to IV, Fisher's group 3, undergoing surgery or coil embolization within 72 h of the onset). With regard to the selection of patients, 34 patients belonging to the control group (no UK injection group) underwent the treatment during the 3-year period from 2001 to 2003, while 35 patients belonging to the UK group underwent the treatment during the 3-year period from 2004 to 2006. The incidence of symptomatic vasospasm was 5/35 with the UK group, but 12/34 with a control group. The UK injection significantly reduced the incidence of symptomatic vasospasm (p = 0.042, Pearson chi-square test), resulting in an improvement shown by the Glasgow Outcome Scale (GOS; p = 0.030, Mann-Whitney U test; Table V). The distribution on the angiographic grading scales for cerebral vasospasm significantly shifted in a positive direction for the UK group (mild 0, moderate 5, severe 0) in comparison with the control group (mild 0, moderate 4, severe 8; p = 0.014, Mann-Whitney U test). This study suggests that combining continuous cerebrospinal drainage and intermittent intrathecal UK injection therapy is a relatively simple and effective method for symptomatic vasospasm prophylaxis in patients with aneurysmal SAH.

BACKGROUND: Very few studies have examined the diversity of human leukocyte antigens (HLA) in the Brazilian renal transplant candidates. METHODS: The frequencies of the HLA‐A, HLA‐B, and HLA‐DRB1 alleles, haplotypes and phenotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Paraná State, southern Brazil. Patients were classified according to the ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans, and Amerindians; browns or “pardos”] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence‐specific oligonucleotide method (PCR‐SSO), combined with Luminex technology. RESULTS: In the analysis of the total samples, 20 HLA‐A, 32 HLA‐B, and 13 HLA‐DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA‐A*02 (25.4%), HLA‐B*44 (10.9%), and HLA‐DRB1*13 (13.9%). The most frequent haplotypes were HLA‐A*01‐B*08‐DRB1*03 (2.3%), A*02‐B*44‐DRB1*07 (1.2%), and A*03‐B*07‐DRB1*11 (1.0%). Significant differences (P < 0.05) were observed in the HLA‐A*68, B*08, and B*58 allele frequencies among ethnic groups. CONCLUSIONS: This study provides the first data on the HLA‐A, HLA‐B, and HLA‐DRB1 allele, phenotype and haplotype frequencies of renal transplant candidates in a population in southern Brazil.

Inhibition of angiotensin II AT1 receptors protects against stroke, reducing the cerebral blood flow decrease in the periphery of the ischemic lesion. To clarify the mechanism, spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were pretreated with the AT1 receptor antagonist candesartan (0.3 mg · kg−1 · d−1) for 28 days, a treatment identical to that which protected SHR from brain ischemia, and the authors studied middle cerebral artery (MCA) and common carotid morphology, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), and protein expression in cerebral microvessels, principal arteries of the Willis polygon, and common carotid artery. The MCA and common carotid artery of SHR exhibited inward eutrophic remodeling, with decreased lumen diameter and increased media thickness when compared with WKY rats. In addition, there was decreased eNOS and increased iNOS protein and mRNA in common carotid artery, circle of Willis, and brain microvessels of SHR when compared with WKY rats. Both remodeling and alterations in eNOS and iNOS expression in SHR were completely reversed by long-term AT1 receptor inhibition. The hemodynamic, morphologic, and biochemical alterations in hypertension associated with increased vulnerability to brain ischemia are fully reversed by AT1 receptor blockade, indicating that AT1 receptor activation is crucial for the maintenance of the pathologic alterations in cerebrovascular circulation during hypertension, and that their blockade may be of therapeutic advantage.

Pharmacological blockade of peripheral and brain Angiotensin II (Ang II) AT 1 receptors protects against brain ischemia. To clarify the protective role of brain AT 1 receptors, we examined the effects of specific antisense oligodeoxynucleotides (AS-ODN) targeted to AT 1 receptor mRNA administered intracisternally to spontaneously hypertensive rats (SHRs), 4 and 7 days before middle cerebral artery (MCA) occlusion, and we determined the infarct size and tissue swelling 24 h after surgery. A single intracisternal injection of AT 1 mRNA receptor antisense oligodeoxynucleotides reduced systemic blood pressure for 5 days and AT 1 receptor binding for at least 4 days in the area postrema and the nucleus of the solitary tract. A similar injection of scrambled oligodeoxynucleotides (SC-ODN) was without effect. Both blood pressure and AT 1 receptor binding returned to normal 7 days after antisense receptor mRNA administration. Both the infarction size and the tissue swelling after middle cerebral artery occlusion were reduced when the antisense oligodeoxynucleotide was administered 7 days, but not 4 days, before the operation. We conclude that 4 to 5 days of decrease in brain AT 1 receptor binding by a single administration of an AT 1 receptor mRNA oligodeoxynucleotide are sufficient to significantly protect the brain against ischemia resulting from total occlusion of a major cerebral vessel.

The role of superoxide anion (O(2)*-) in neuronal cell injury induced by reactive oxygen species (ROS) was examined in PC12 cells using pyrogallol (1,2,3-benzenetrior), a donor to release O(2)*-. Pyrogallol induced PC12 cell death at concentrations, which evidently increased intracellular O(2)*-, as assessed by O(2)(*-)-sensitive fluorescent precursor hydroethidine (HEt). Caspase inhibitors, Z-VAD-FMK and Z-Asp-CH(2)-DCB, failed to protect cells from injury caused by elevation of intracellular O(2)*-, although these inhibitors had effects on hypoxia- or hydrogen peroxide (H(2)O(2))-induced PC12 cell death. Two known O(2)*- scavengers, Tiron (4,5-dihydroxy-1,3-benzenedisulfonic acid) and Tempol (4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxyl) rescued PC12 cells from pyrogallol-induced cell death. Hypoxia/reoxygenation injury of PC12 cells was also blocked by Tiron and Tempol. Further understanding of the underlying mechanism of the protective effects of these radical scavengers reducing intracellular O(2)*- on neuronal cell death may lead to development of new therapeutic treatments for hypoxic/ischemic brain injury.

We report two instructive cases of ruptured dissecting aneurysm of the basilar artery. Although stent-assisted endovascular treatment was successful, recurrent bleeding occurred 4 h after the procedure in one patient, and the other's basilar artery occluded 6 days after the procedure. These cases suggest that the high porosity of currently available stents may be insufficient to induce intraluminal thrombosis and merely stenting may fail to prevent bleeding, while postoperative anticoagulation alone may be inadequate to prevent occlusion of the stented vessel.

A 46-year-old woman presented with a dissecting aneurysm of the right middle cerebral artery manifesting as subarachnoid hemorrhage followed by hemorrhagic infarctions. The aneurysm was clipped and wrapped. However, serial angiography showed progression of the lesion, which was probably responsible for the clinical course of this patient. Intracranial dissecting aneurysms are less common, and the natural history of these lesions is unclear. Conservative management might be preferable in this patient.

Ca2+ influx is one of the main causative events in hypoxic PC12 cell death, because an extracellular Ca2+ chelator, ethylene glycol bis (2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) inhibited and Ca2+ ionophore A23187 mimicked the hypoxic cell death. The hypoxic cell death was markedly prevented by a broad spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-FMK) as well as a calpain inhibitor, calpeptin, as assessed by nuclear staining with Hoechst 33258 and lactate dehydrogenase release. The processing of procaspase-3 was inhibited by z-VAD-FMK, but not by calpeptin. In contrast, z-VAD-FMK failed to block the proteolytic cleavage of fodrin-alpha, a preferential substrate for calpain. On the other hand, degradation of actin and fodrin-alpha was prevented by calpeptin but not by z-VAD-FMK. In addition, not only protein kinase C (PKC)-alpha but also PKC-delta were cleaved to generate approximately 46 kDa fragments. The PKC fragmentation was inhibited by calpeptin but not by z-VAD-FMK. These findings suggest that the extracellular Ca2+ influx induced by hypoxic stress activates calpain, resulting in the degradation of cytoskeletal proteins and generation of PKC fragments almost independently of caspase activation. Therefore, calpain may play an important role in hypoxic PC12 cell death.

Ceramide has recently been regarded as a potential mediator of apoptosis. In the present study, the effects of Bcl-2 and Bax on the ceramide-mediated apoptotic pathways were examined in glioma cells overexpressing Bcl-2 or Bax. Etoposide, cisplatin and tumor necrosis factor-alpha induced apoptosis of C6 rat glioma cells which was associated with ceramide formation due to activation of neutral sphingomyelinase, followed by release of mitochondrial cytochrome c into the cytosol and activation of caspases-9 and -3. The growth of C6 cells stably overexpressing either Bcl-2 or Bax was almost equal to that of the vector-transfected cells. Bax overexpression enhanced etoposide-induced apoptosis through acceleration of cytochrome c release and caspases activation. However, Bax had no effect on ceramide formation. Similar findings were obtained in C6 cells and U87-MG human glioblastoma cells which were transiently overexpressed with Bax. In contrast, Bcl-2 overexpression resulted in a retardation of the apoptotic process via prevention of cytochrome c release and caspases activation, and ceramide formation was also blocked when Bcl-2 was highly overexpressed in glioma cells. In addition, transient overexpression of Bcl-xL also exerted inhibitory effects on ceramide formation and apoptotic cell death induced by etoposide. These results indicate that Bax promotes apoptosis regardless of ceramide formation and that Bcl-2 or Bcl-xL prevents ceramide formation by repressing neutral sphingomyelinase as well as ceramide-induced cytochrome c release. Oncogene (2000) 19, 3508 - 3520

SUMMARY: We present 3 cases of extracranial head and neck schwannomas exhibiting fluid-fluid levels. In the described cases, CT and MR imaging showed predominantly cystic components, intermixed with cellular components. Histopathologic examinations of excised specimens revealed hemosiderin deposition, reflecting intratumoral hemorrhages, which was presumably a cause of fluid-fluid levels. Although fluid-fluid levels are nonspecific findings, schwannoma should be considered when radiologic images demonstrate marked cystic formation with fluid-fluid levels in extracranial head and neck tumors.

This study is designed to determine whether patients with aneurysmal subarachnoid hemorrhage have mutations in the phospholipase C-delta 1 (PLC-delta 1) gene, which was identified as a gene responsible for hypertension in spontaneously hypertensive rats. Seventy-two cases (31 male and 41 female) with intracranial saccular aneurysms were analyzed. The mean age was 60.1 +/- 11.5 years (mean +/- SD) (range 24-85 years). There were 35 patients (48.6%) with hypertension, 5 (6.9%) with diabetes mellitus, 12 (16.7%) with hyperlipidemia, 8 (11.1%) with ischemic heart disease, and 25 (34.7%) who were active smokers. The location of aneurysm was distributed as follows: 33 (33%) were at anterior cerebral artery, 23 (23%) were at middle cerebral artery, 28 (28%) were at internal carotid artery, and 16 (16%) were at vertebro-basilar artery. Six patients (8.3%) had a family history of intracranial aneurysms. There were 20 patients (27.8%) with multiple aneurysms, and 8 patients (11.1%) with a large or giant aneurysm. The four regions of PLC-delta 1 gene (bases 1099-1271, 1254-1401, 1343-1481, and 1882-2023) where genetic mutations were found in spontaneously hypertensive rats, were screened by PCR-SSCP analysis and their nucleotide sequences of all patients were determined. However, no mutations were detected in all patients. These results suggest that mutations of PLC-delta 1 gene previously implicated in hypertensive factor in rats may not be the case with human patients and therefore may be poorly related with aneurysmal subarachnoid hemorrhage.

Object. Endoglin, a transforming growth factor β—binding protein, is a glycoprotein expressed on the surface of human vascular endothelial cells. Mutations of this gene are responsible for hereditary hemorrhagic telangiectasis and are associated with sporadic intracerebral hemorrhage as a risk factor. The purpose of this study was to examine the polymorphism of this gene in patients with intracranial aneurysms.Methods. The authors identified the mutations and insertion polymorphism around exon 7 of the endoglin gene in 82 patients with intracranial saccular aneurysms (aneurysm group) and 114 control volunteers (control group).A 6-base insertion (GGGGGA) was found in intron 7 at 26 bases beyond the 3′ end of exon 7. The homozygous insertion of intron 7 of the gene was present in 20.7% of the aneurysm group compared with 6.1% of the control group (χ2 = 9.837, p = 0.0073). The insertion allele frequency was significantly higher in the aneurysm group (67 [40.8%] of 164) than that in the control group (63 [27.6%] of 228) (χ2 = 7.48, p = 0.0062). The most notable clinical characteristic of the 17 patients with homozygous insertion in the aneurysm group was the relatively high percentage of patients with hypertension and of those with multiple aneurysms.Conclusions. The data provide evidence of an association between aneurysm development and a polymorphism at a genetic variant of endoglin in patients with these lesions.

The profile of patients undergoing haemodialysis in the dialysis unit of Hospital Santa Casa de Maringa, Maringa PR Brazil, is provided. A questionnaire on social and economic data and underlying diseases prior to the Chronic Kidney Disease (CKD) identified the patients' profile. The project was approved by the Ethics Committee of the institution. Eighty-three patients, with 54.21% males, were interviewed. Age bracket ranged between 20 and 59 years in 65.06% of patients. Only 27.71% maintained jobs after the diagnosis and the start of treatment; 63.86% had an average personal income between 1 and 3 minimum wages; 63.85% did not practice any physical activity. Moreover, 53.01% belonged to the European-Brazilian white group; 20.48% to the Afro-Brazilian brown group; 19.28% to the Afro-Brazilian Negro group; 6.02% to other ethnic groups. Further, 85.54% patients reported having an underlying disease prior to the CKD, namely, 61.45% were hypertensive; 31.33% were diabetics and 20.48% had other diseases. Results show the need of a greater attention to these patients' health care to reduce the negative impacts related to the chronic disease focused.

Retrograde flow through the anterior spinal artery (ASA) from the cervical vertebral artery (VA) to the intracranial distal VA due to disrupted perfusion caused by bilateral VA occlusion is rare. We report two cases of hemodynamic vertebrobasilar circulatory insufficiency caused by bilateral VA occlusion. In these patients, the ASA filled in the retrograde direction, and provided collateral support to the ipsilateral posterior inferior cerebellar artery. The patients were treated with drip intravenous infusion of edaravone and/or argatroban. One patient had a good collateral supply from the posterior communicating artery and recovered almost completely within one month, but the other did not and lapsed into a coma, with generalized hyperreflexia, pin-point pupils, and ataxic respiration. Severe calcified lesions on three-dimensional computed tomography angiography at the occlusion site in the second patient indicated direct surgery including right superficial temporal artery to superior cerebellar artery anastomosis, rather than the endovascular approach. Retrograde flow through the ASA may be observed in this type of critical situation, and may be an important source of collateral supply to the posterior fossa territory.

The detection of asymptomatic lacunar infarcts on magnetic resonance (MR) images are important tasks for radiologists to ensure the prevention of severe cerebral infarction. However, their accurate identification is often difficult task. Therefore, the purpose of this study is to develop a computer- aided diagnosis scheme for the detection of lacunar infarcts. Our database consisted of 1,143 T1- and 1,143 T2-weighted images obtained from 132 patients. We first segmented the cerebral region in the Tl- weighted image by using a region growing technique. For identifying the initial lacunar infarcts candidates, white top-hat transform and multiple-phase binarization were then applied to the T2- weighted image. For eliminating false positives (FPs), we determined 12 features, i.e., the locations x and y, density differences in the Tl- and T2-weighted images, nodular components (NC), and nodular & linear components (NLC) from a scale 1 to 4. The NCs and NLCs were obtained using filter bank technique. The rule-based scheme and a neural network with 12 features were employed as the first step for eliminating FPs. The modular classifier was then used for eliminating three typical sources of FPs. As a result, the sensitivity of the detection of lacunar infarcts was 96.8% with 0.30 FP per image. Our computerized scheme would assist radiologists in identifying lacunar infarcts on MR images.

Background Aneurysms arising from the distal portion of the SCA are relatively rare. A case is presented of an aneurysm arising from the cortical segment of the SCA. Case Description A 45-year-old woman was admitted to our institution because of severe headache. Radiological examination revealed SAH caused by rupture of the aneurysm located in the cortical segment of the SCA and was treated successfully with coil embolization. Conclusions This type of aneurysms may be difficult to treat surgically because of its inaccessibility and of the common difficulty in preserving the involved parent artery. In view of the previously reported cases, these peripheral aneurysms of the SCA often have undefinable necks, as is shown in our case, which makes a reconstructive endovascular and/or surgical technique more or less difficult. However, the overall outcome is almost always favorable, even if surgical treatment results in proximal parent artery occlusion or trapping with surgical clips. These results imply that an equivalent endovascular approach to these rare lesions can be an effective alternative method of management.

Rationale and Objectives The detection and management of asymptomatic lacunar infarcts on magnetic resonance (MR) images are important tasks for radiologists to ensure the prevention of severe cerebral infarctions. However, accurate identification of the lacunar infarcts on MR images is a difficult task for the radiologists. Therefore the purpose of this study was to develop a computer-aided diagnosis scheme for the detection of lacunar infarcts to assist radiologists’ interpretation as a “second opinion.” Materials and Methods Our database comprised 1,143 T1- and 1,143 T2-weighted images obtained from 132 patients. The locations of the lacunar infarcts were determined by experienced neuroradiologists. We first segmented the cerebral region in a T1-weighted image by using a region growing technique for restricting the search area of lacunar infarcts. For identifying the initial lacunar infarcts candidates, a top-hat transform and multiple-phase binarization were then applied to the T2-weighted image within the segmented cerebral region. For eliminating the false positives (FPs), we determined 12 features—the locations x and y, signal intensity differences in the T1- and T2-weighted images, nodular components from a scale of 1 to 4, and nodular and linear components from a scale of 1 to 4. The nodular components and the linear components were obtained using a filter bank technique. The rule-based schemes and a support vector machine with 12 features were applied to the regions of the initial candidates for distinguishing between lacunar infarcts and FPs. Results Our computerized scheme was evaluated by using a holdout method. The sensitivity of the detection of lacunar infarcts was 96.8% (90/93) with 0.76 FP per image. Conclusions Our computerized scheme would be useful in assisting radiologists for identifying lacunar infarcts in MR images.

Aim To evaluate the diversity of alleles and haplotypes of HLA-A, -B and -DRB1 in renal transplant candidates in a population in southern Brazil. Methods The frequencies of the HLA-A, -B and -DRB1 alleles and haplotypes were studied in 522 patients with chronic renal failure, renal transplant candidates, registered at the Transplant Centers in north/northwestern Parana State, southern Brazil. Patients were classified according to ethnic group (319 whites [Caucasians], 134 mestizos [mixed race descendants of Europeans, Africans and Amerindians; browns or “pardos”] and 69 blacks). The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology. Results In the analysis of the total samples, 20 HLA-A, 32 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent allele groups for each HLA locus were HLA-A ∗ 02 (25.4%), HLA-B ∗ 44 (10.9%) and HLA-DRB1 ∗ 13 (13.9%). The most frequent haplotypes were HLA-A ∗ 01-B ∗ 08-DRB1 ∗ 03 (2.3%), A ∗ 02-B ∗ 44-DRB1 ∗ 07 (1.2%) and A ∗ 03-B ∗ 07-DRB1 ∗ 11 (1.0%). Significant differences ( p ∗ 68, B ∗ 08 and B ∗ 58 allele frequencies among ethnic groups. Conclusions Data from this study provide knowledge of the frequencies of the HLA-A, -B and -DRB1 allele and haplotypes in renal transplant candidates from north/northwestern Parana state, southern Brazil.

Background Distal aneurysms of the anterior inferior cerebellar artery (AICA) are rare. Most of the reported cases have been located near the internal auditory meatus. Among these cases, only six located in the internal auditory meatus have been reported in the literature. Methods A 64-year-old female presented with sudden onset of severe headache. Computed tomography (CT) revealed moderate subarachnoid hemorrhage and Gd-DTPA enhanced magnetic resonance imaging (MRI) showed a small high-intensity mass at the right cerebellopontine angle. Although initial digital subtraction angiography (DSA) showed no vascular abnormalities, repeated DSA disclosed a saccular aneurysm at the top of the meatal loop of the right AICA. The patient underwent a suboccipital craniectomy on the 18th day after the hemorrhage. Results In this case, the aneurysm was completely buried in the internal auditory meatus. After unroofing the meatus, the aneurysm was successfully clipped. After 3 months of hospitalization, the patient was discharged with right-sided deafness, partial facial palsy, and no other complications. Conclusion We discuss some of the clinical features and pitfalls in the surgical management of intracanalicular AICA aneurysms and review previous reports of similar cases.

A 21-year-old woman with severe mitral valve regurgitation due to infectious endocarditis was transferred to our institute in a deep coma with intracerebral hemorrhage and acute subdural hematoma. She had no history of head injury. Brain computed tomography revealed left frontoparietal intracerebral hematoma and adjacent acute subdural hematoma that were evacuated on the day of admission, but the distal middle cerebral artery (MCA) aneurysm remained undetected. Follow-up cerebral angiography demonstrated the distal MCA aneurysm, which had enlarged by 25% at 2 weeks following the first operation. The aneurysm originated from a branch of the angular artery and was successfully resected on Day 22. Histological examination of the aneurysm section showed no infectious nature, but the final diagnosis was infectious intracranial aneurysm based on the presence of infectious endocarditis.

Background: Dissecting aneurysm of the posterior inferior cerebellar artery (PICA) uninvolved with the vertebral artery is rare. The exact pathohistological diagnosis might result in ‘unknown' because the underlying pathoanatomical features are, for a variety of reasons, not always identified. Case description: We report herein two cases of dissecting aneurysm harbored in different segments of the distal posterior inferior cerebellar artery. In our cases, after trapping the PICA at both just proximal and distal to the aneurysm, the abnormal portion was successfully resected with/without an end-to-end anastomosis. The first patient made a good recovery, while the other died 2 days after the surgery. Although its pathogenetic etiology was unidentified in the second case, the formation of dissecting aneurysm had resulted from a segmental mediolytic arteriopathy in the first case. Conclusion: This is the first report of a segmental mediolytic arteriopathy possibly being identified as causing an isolated dissecting aneurysm at this site.

Background and Purpose— Pretreatment with angiotensin II AT 1 receptor antagonists protects against cerebral ischemia. We studied whether modulation of cerebral blood flow (CBF) and morphometric changes in brain arteries participated in this protective mechanism. Methods— We pretreated adult spontaneously hypertensive rats with equally antihypertensive doses of candesartan (0.1 or 0.3 mg/kg per day), nicardipine (0.1 mg/kg per day), or captopril (3.0 mg/kg per day) for 3 or 28 days via subcutaneous osmotic minipumps followed by permanent left middle cerebral artery (MCA) occlusion distal to the origin of the lenticulostriate arteries. We measured CBF by autoradiography with 4-iodo-[ N -methyl- 14 C]antipyrine 3 hours after operation and the areas of infarct and tissue swelling 24 hours after operation. Morphometric changes in the MCA were studied after antihypertensive treatment. Results— Twenty-eight days of candesartan pretreatment decreased the infarct area by 31%; reduced the CBF decrease at the peripheral area of ischemia and the cortical volume of severe ischemic lesion, where CBF was Conclusions— Angiotensin II system inhibition protects against neuronal injury more effectively than calcium channel blockade. Protection after AT 1 receptor blockade is not directly correlated with blood pressure reduction but with normalization of MCA media thickness, leading to increased arterial compliance and reduced CBF decrease during ischemia at the periphery of the lesion.

Pre-transplant sensitization to human leukocyte antigens (HLA) is a risk factor for graft failure. Studies of the immunological profile related to anti-HLA antibodies in Brazilian renal transplant candidates are few. In this study, we evaluated the humoral immune response to HLA antigens in 269 renal transplant candidates, in Paraná State, Brazil. The HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO) combined with Luminex technology, using an SSO-LABType commercial kit (One Lambda, Inc., Canoga Park, CA, USA). The percentages of panel-reactive antibodies (PRA) and the specificity of anti-HLA antibodies were determined using the LS1PRA and LS2PRA commercial kits (One Lambda, Inc.). The PRA-positive group consisted of 182 (67.7%) patients, and the PRA-negative group of 87 (32.3%) patients. The two groups differed significantly only with respect to gender. Females were the most sensitized. Among the 182 patients with PRA- positive, 62 (34.1%) were positive for class I and negative for class II, 39 (21.4%) were negative for class I and positive for class II, and 81 (44.5%) were positive for both classes I and II. The HLA-A*02, A*24, A*01, B*44, B*35, B*15, DRB1*11, DRB1*04 and DRB1*03 allele groups were the most frequent. The specificities of anti-HLA antibodies were more frequent: A34, B57, Cw15, Cw16, DR51, DQ8 and DP14. This study documented the profile of anti-HLA antibodies in patients with chronic renal failure who were on waiting lists for an organ in Paraná, and found high sensitization to HLA antigens in the samples.

We investigated the polymorphism of human leukocyte antigens (HLA) and Duffy erythrocyte antigens in chronic kidney disease (CKD) patients in southern Brazil. One hundred and eighty-three CKD patients, over 18 years old, on hemodialysis, were included. HLA-A, -B and -DRB1 typing was performed using the LABType®SSO (One Lambda, Inc.). Duffy phenotypes were determined by gel column agglutination using anti-Fy(a) and anti-Fy(b) monoclonal anti-sera. The patients' predominant ages ranged between 51 and 70 years (43%) and the predominant gender, ethnic group and dialysis period were, respectively, male (62%), white (62%) and 1-3 years (40%). The highest and lowest frequencies of Duffy phenotypes were Fy(a+b+) and Fy(a-b-), respectively. Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The most frequent HLA allele groups were HLA-A*01, -A*02, -A*03, -A*11, -A*24; HLA-B*07, -B*15, -B*35, -B*44, -B*51; HLA-DRB1*03, -DRB1*04, -DRB1*07, -DRB1*11 and -DRB1*13. Statistically significant differences were observed in the Duffy and HLA polymorphisms compared between CKD patients and healthy subjects. The Fy(a+b-) phenotype (p

The purpose of this study was to clarify the occurrence rate and characteristics of spinal injuries caused by snowboarding that were sustained at the Okumino skiing area in Gifu Prefecture, Japan, from 1988 to 2000.This study was a retrospective review of 13,490 cases of snowboard- or ski-related injury treated at Sumi Memorial Hospital over this period.A total of 7,188 patients sustained snowboard-related injuries, and 238 of these had spinal injuries caused by snowboarding (3.3%), whereas 6,302 patients sustained ski-related injuries, and 86 of these had spinal injuries caused by skiing (1.4%). Although there were no significant differences in the difficulty of slope, location of vertebral fracture, or spinal cord injury between snowboarders and skiers, the incidence of transverse process fractures was significantly higher in snowboard-related than in skiing-related injury (p0.05). In addition, there was a significantly higher incidence of spinal injury among beginner snowboarders than among beginner skiers (p = 0.04). Furthermore, intermediate or expert snowboarders were more likely to be injured because of jumping than beginners (p0.001), whereas about 70% of spinal injuries caused by skiing resulted from a simple fall.Spinal injuries sustained while snowboarding are increasing considerably in incidence and are characterized as complex injuries. We must educate young snowboarders of the risk of this sport, to prevent these serious injuries.

Aim To evaluate the humoral immune response to HLA antigens in Brazilian renal transplant candidates. Methods The humoral immune response to HLA antigens was studied in 269 renal transplant candidates from the north/northwest of Parana state, Brazil. HLA typing was performed by the polymerase chain reaction sequence-specific oligonucleotide method (PCR-SSO), combined with Luminex technology using the LABType SSO kit (One Lambda, Inc., Canoga Park, CA, USA). Panel reactive antibodies (PRA) and HLA-specific antibodies determination were performed using the LABScreen (Luminex technology) LS1PRA and LS2PRA kits (One Lambda, Inc.). The Fisher’s exact test and Student’s t-test were used to compare the demographic characteristics and potential risk factors for anti-HLA antibody production (pregnancies, blood transfusions and previous transplants) between PRA-positive and PRA-negative groups. Results One hundred and eighty two (67.7%) patients had positive PRA. Potential risk factors for anti-HLA antibody production showed no significant differences between PRA-positive and PRA-negative groups. Only gender was statistically different between these groups, showing that female group was the most sensitized (p Conclusions The data of this study allowed the knowledge of HLA antibodies profile in renal transplant candidates from the Parana State (Brazil), showing high sensitization to HLA antigens. Further studies are needed to evaluate the influence of alloreactivity and HLA polymorphisms in the end-stage renal disease and the evolution of transplantation.

Aim The aim of this study was to evaluate the polymorphisms of human leukocyte antigen (HLA) and Duffy erythrocyte antigen in nephropathic patients from southern Brazil. Methods One hundred and eighty three chronic kidney patients from southern Brazil participated in this study. HLA typing was performed using the LABType SSO kits locus HLA-A, -B and-DRB1 (One Lambda, Inc.). Duffy phenotypes were defined by the gel agglutination method using monoclonal anti-Fya and anti-Fyb antisera. Fisher’s exact test was employed for statistical analysis. Odds Ratio (OR) and Confidence Interval (CI) at 95% were calculated. Data from other studies with healthy individuals (voluntary bone marrow donors) were used for the comparison of analysis. Results In the analysis of the total samples, Fy(a+b+) phenotype was the most frequent (35%) and Fy(a-b-) phenotype was the rarest (5%). Nineteen HLA-A, 30 HLA-B and 13 HLA-DRB1 allele groups were identified. The 15 most frequent HLA allele groups were HLA-A∗01, A∗02, A∗03, A∗11, A∗24, HLA-B∗07, B∗15, B∗35, B∗44, B∗51, HLA-DRB1∗03, DRB1∗04, DRB1∗07, DRB1∗11 and DRB1∗13. The frequencies of Fy(a+b-) and Fy(a+b+) phenotypes of this study compared with healthy individuals from the same region, showed statistically significant difference with p Conclusions The polymorphism of these two markers when compared between the nephropathic patients from southern Brazil and other studies, suggest that the Duffy antigen and HLA allele groups may be engaged with chronic kidney disease (CKD). Further studies are needed to evaluate the influence of these markers in the evolution of CKD, as well as the evolution of transplantation.

During hypoxic incubation (1% O2) of PC12 cells, the PLD activity was transiently increased within 12h, followed by a gradual decrease. In the in vitro assay, the increased PLD activity was independent of GTPgammaS required for PLD1 or of oleic acid for PLD(OA), suggesting the activation of PLD2. The level of PLD2 protein showed no change up to 12h but a gradual decrease after 24 h. Pretreatment of cells with S. chromofuscus PLD resulted in inhibition of hypoxia-induced apoptotic cell death. In contrast, 1-butanol, but not 2-butanol, potentiated cell death. Moreover, the number of apoptotic cells significantly reduced in PC12 cells over-expressing PLD2. These results raise the possibility that PLD2 activation may play an anti-apoptotic role in hypoxia-induced cell death.

The present study was designed to elucidate the relationship between p53 and ceramide, both of which are involved in apoptotic signaling. Treatment of human glioma cells with etoposide caused apoptosis only in cells expressing functional p53. p53 activation was followed by the formation of reactive oxygen species (ROS), superoxide anion (O2-*) measured by hydroethidium oxidation into ethidium and hydrogen peroxide (H2O2) measured by oxidation of 2',7'-dichlorofluorescin (DCFH) into 2',7'-dichlorofluorescein (DCF), which was accompanied with ceramide generation through the activation of neutral, but not acid, sphingomyelinase. Superoxide dismutase (SOD), a selective antioxidant for O2-*, had no effects on p53 expression but inhibited ceramide generation and apoptotic cell death caused by etoposide. However, catalase, a specific antioxidant for H2O2, only weakly inhibited and sodium formate, a hydroxyl radical (* OH) scavenger, unaffected etoposide-induced apoptosis. Like etoposide-induced cell death, treatment of glioma cells with the O2-*-releasing agent, pyrogallol, induced typical apoptosis and ceramide generation even in the presence of catalase. In contrast, human glioma cells lacking functional p53, either due to mutation or the expression of E6 protein of human papillomavirus, were highly resistant to etoposide and exhibited no significant change in the ceramide level. Moreover, expression of functional p53 protein in glioma cells expressing mutant p53 using a temperature-sensitive human p53(Val138) induced ceramide accumulation by the activation of neutral sphingomyelinase which was dependent on the generation of O2-*. Taken together, these results suggest that p53 may modulate ceramide generation by activation of neutral sphingomyelinase through the formation of O2-*, but not its downstream compounds H2O2 or * OH.

Reduced glutathione (GSH) and N-acetylcysteine (NAC), but not other antioxidative or reducing agents, were found to inhibit cell death, both apoptosis and necrosis, induced by hypoxia in naive and nerve growth factor-differentiated PC12 cells. The level of intracellular total GSH decreased time-dependently during hypoxia, but exogenously added GSH prevented such a decrease in GSH. Pretreatment of cells with exogenous GSH or NAC resulted in inhibition of both neutral sphingomyelinase (SMase) activation and ceramide formation during hypoxia. In the in vitro assay system, neutral SMase activity was inhibited dose-dependently by GSH and NAC. Activation of caspase-3 induced by hypoxia was also inhibited by either GSH or NAC. NAC but not GSH inhibited caspase-3 activation induced by C2-ceramide. These results suggest that GSH protects cells from hypoxic injury by direct inhibition of neutral SMase activity and ceramide formation, resulting in inhibition of caspase-3 activation, and that NAC exerts an additional inhibitory effect(s) downstream of ceramide.

A 61-year-old female presented with a unique case of moyamoya disease associated with pulmonary sarcoidosis. She was admitted for sudden onset of left temporalgia with episode of numbness on face, tongue, and upper extremity on the right side. The next morning, she had symptoms of Gerstmann syndrome and her ability to speak was disturbed. Her medical history included radical resection of lung cancer on the right side. She had no symptoms of pulmonary sarcoidosis. Neuroimaging showed an infarction in the left occipital lobe. Angiography showed occlusions of the bilateral internal carotid arteries at the supraclinoid portions. Subsequently, a left superficial temporal artery-middle cerebral artery anastomosis with encephalo-myo-synangiosis was performed. Ninety-three days after admission, she suddenly developed dyspnea which resulted in death 3 hours later. Autopsy findings showed typical epithelioid granulomas of sarcoid type in the lymph nodes of the peribronchus, lung, and liver. Thrombotic emboli were found in the bilateral pulmonary arteries, and marked fibrous intimal thickening in the bilateral internal carotid arteries. Immunological reaction with inflammatory events may cause pathological changes in patients with moyamoya disease or sarcoidosis. The co-incidence in this case suggests that some common inflammatory events may be involved in the pathogenesis of these diseases.

O objetivo deste estudo foi analisar a prevalencia de dialise em mulheres no estado do Parana, municipio de Maringa e regiao metropolitana. Estudo quantitativo, descritivo, de corte transversal. Foi estudada a prevalencia de dialise em mulheres no estado do Parana, municipio de Maringa e regiao metropolitana, no periodo de 1999 a 2007, atraves do Sistema de Informacoes Ambulatoriais do Sistema Unico de Saude (SIA/SUS), no programa do Departamento de Informatica do Sistema Unico de Saude (DATASUS). Houve aumento da taxa de prevalencia de dialise em mulheres no estado do Parana, municipio de Maringa e regiao metropolitana no periodo de 1999 a 2007. No estado do Parana, houve um crescimento de 1,71 mulheres em dialise por 100.000 habitantes do sexo feminino anualmente (p?0,05), as faixas etarias 30 a 59 anos e 60 anos e mais se revelaram como fatores de risco para realizar dialise no sexo feminino. No municipio de Maringa e regiao metropolitana, houve um crescimento de 0,88 de mulheres em dialise por 100.000 habitantes do sexo feminino anualmente (p?0,05), a faixa etaria 60 anos e mais se revelou como fator de risco para realizar dialise no sexo feminino.

Aim To analyse the distribution of HLA class I (A and B) and HLA class II (DRB1) alleles of chronic renal patients and the association with negative and positive PRA, based in sensitization events. Methods One hundred fifty chronic kidney patients from southern region of Brazil, were subdivided into 4 groups, according to the patients’ PRA results, regardless of the occurrence or not of one of the sensitiveness events, such as pregnancy (P), transfusion (S) or transplantation (T), characteristics grouped and identified as PST: Group 1, PRA = 0 (n = 79); Group 2, PRA > 0 (n = 71); Group 3, PRA between 0 and 50% (n = 43); Group 4, PRA > 50% (n = 28). Control group comprised 71 nonsensitized chronic kidney patients (PRA = 0), classified as positive for any of the PST events. HLA genotyping was undertaken by the RSSO-LABType methodology. PRA were obtained by LABScreen methodology. Fisher’s exact test and Odds Ratio (OR) with 95% confidence interval (CI) were used for statistical analysis. Further, p rates were significant when lower than 0.05. Results No significant differences with regard to loci HLA-A, HLA-B and HLA-DRB1 were found in Group 1 when compared to control group. No significant differences with regard to loci HLA-A and HLA-DRB1 were found in Groups 2 and 3. However, allele HLA-B ∗ 08 had a significant negative association in Group 2 (p = 0.0258; OR = 0.27; 95%IC = 0.09-0.83) and in Group 3 (p = 0.0334; OR = 0.22; 95%IC = 0.05-0.98) when compared to control group. Significant positive association in Group 4 was found for alleles HLA-A ∗ 26 (p= 0.0101; OR = 4.57; 95%IC = 1.42-14.64), HLA-B ∗ 58 (p = 0.0074; OR = 13.82; 95%IC = 1.58- 121.17) and HLA-B ∗ 13 (p = 0.0218; OR = 17.97; 95%IC= 0.91-353.64). No significant differences were found within the HLA-DRB1 alleles when compared to control group. Conclusions There are HLA alleles that influence chronic kidney patients to sensitization of HLA molecules. HLA Class I alleles seem to be more involved to susceptibility and/or resistance to the development of anti-HLA antibodies.