Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with sickle cell anemia (SCA) carry a 200-fold increased risk for cerebral infarction. Stroke can be the result of small-vessel (SV) or large-vessel (LV) disease. However, it is unknown whether these subtypes result from the same pathophysiologic processes. Complete HLA genotyping was performed on 231 eligible children previously enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD). Cerebral infarction on magnetic resonance imaging (MRI) was documented in 71 patients, and 160 patients had negative findings on MRI. Based on MRI/magnetic resonance angiography (MRA) findings, infarct size, and location, 36 patients were classified as having LV stroke and 35 as having SV stroke. When comparing the total MRI+ group with the MRI- group, HLA DPB1*0401 was associated with increased stroke risk (P =.01), whereas DPB1*1701 (P =.02) conferred protection from stroke. These DPB1 associations with stroke were attributed to the SV stroke group, in whom DPB1*0401 was associated with susceptibility (P =.003) and DPB1*1701 with protection from stroke (P =.06). In the LV stroke subgroup, HLA-A*0102 (P =.02) and -A*2612 (P =.007) conferred susceptibility, whereas -A*3301(P =.04) protected from stroke. These results suggest that specific HLA alleles influence stroke risk and appear to contribute differently to SV and LV stroke subtypes. The distinct HLA associations with SV and LV stroke suggest that different pathologic processes may be involved in the development of stroke in children with SCA. If these results are confirmed in a larger study, HLA type may serve as a useful marker for the early identification of SCA patients at high risk for stroke.
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PMID:Distinct HLA associations by stroke subtype in children with sickle cell anemia. 1251 10

Hypertension accelerates the deterioration of the function of transplanted kidney. Aggressive control of blood pressure is recommended in post-transplant period when maintenance levels of the immunosuppressive drugs are achieved. The aim of this study was to compare the transplanted kidney function in two groups of the hypertensive patients matched for age, sex, HLA-mismatches, early post-transplant course, standard triple immunosuppression and hypotensive therapy during 3 years of follow-up. The mean through-levels of cyclosporine A in whole blood were similar in both groups and did not exceed 185 ng/ml. Group 1 consisted of 28 patients with satisfactory blood pressure (BP) control (arterial pressure below 160/90 mmHg) and group 2 consisted of 21 patients with unsatisfactory BP control. Slow but significant increase of the mean creatinine levels was observed in group 2 during 3 years of follow up, whereas in group 1 graft function remained stable. Cardiovascular events were observed only in group 2--stroke in one patient and death because of heart failure in one patient.
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PMID:[Effect of hypertension on function of the transplanted kidney--3 years follow-up]. 1505 33

The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and -238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been independently correlated with numerous diseases. Alleles TNF(-376A) and TNF(-238A) are normally found throughout the world with very low frequencies. We investigated the frequency of these SNPs in Sicilian subjects hospitalized after traumatic brain injury and in three groups of subjects from northern Sardinia: healthy subjects and individuals with multiple sclerosis or ischemic stroke. While no significant difference was found between healthy and disease subjects, the frequency of TNF(-376A) and TNF(-238A) was elevated up to 10 times in Sardinia compared to Sicily and other populations throughout the world. These elevated frequencies may be the result of genetic drift or of selective pressure on TNF itself or on neighboring genes, including the HLA. Malaria, endemic to Sardinia until the end of the 1940s, and the bubonic plague, are among the possible causes of selection. These findings indicate that Sardinia is an ideal location to further elucidate the correlation between TNF or HLA polymorphisms and diseases, including multiple sclerosis and type-I diabetes, present with an unusually high frequency and co-morbidity in Sardinia.
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PMID:High frequency of TNF alleles -238A and -376A in individuals from northern Sardinia. 1514 31

Patients with sickle cell disease (N = 3) and thalassemia (N = 1) with high-risk features received hematopoietic stem cell transplantations (HCT) to induce stable (full or partial) donor engraftment. Patients were 9-30 years of age. Fludarabine, rabbit anti-thymocyte globulin (ATG), and 200 cGy total body irradiation were administered pre-transplant. Patients received bone marrow (N = 3) or peripheral blood stem cells (N = 1) from HLA-identical siblings, followed by mycophenolate mofetil and cyclosporine for post-grafting immunosuppression. Significant lymphopenia, but only moderate neutropenia and thrombocytopenia developed post transplant. No grade IV nonhematological toxicities or acute graft-versus-host disease (GVHD) were observed. At 3 months after transplantation, three of four patients had evidence of donor myeloid chimerism (range, 15-100%). However, after post transplant immunosuppression was discontinued, graft rejection occurred in all but one patient. This patient is now doing well 27 months post transplant with full donor engraftment. One patient died after a second transplant, and another patient experienced a stroke as her graft was being rejected. These results suggest that stable donor engraftment after nonmyeloablative HCT is difficult to achieve among immunocompetent patients with hemoglobinopathies and that new approaches will need to be developed before wider application of this transplantation method for hemoglobinopathies.
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PMID:Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. 1553 1

A patient with intracerebral hemorrhage is considered ineligible for hematopoietic stem cell transplantation (HSCT). We report a 49-year-old woman with myelodysplastic syndrome (MDS) complicated by refractoriness to platelet transfusion and intracerebral hemorrhage, who underwent allogeneic bone marrow transplantation from an HLA-identical unrelated male donor. Nine days before the scheduled transplantation, she developed dysarthria and right hemiparesis; computed tomography (CT) of the brain disclosed an acute hematoma in the left parietal lobe exceeding 3 cm in diameter. She underwent conditioning with reduced-intensity, including fludarabine (30 mg/m2/day on days -8 to -3), busulfan (4 mg/kg/day on days -6 and -5), and total body irradiation (4 Gy on day -2). Two weeks after transplantation, dysarthria and right hemiparesis began to resolve, and CT showed spontaneous resolution of the hematoma. Simultaneously, engraftment was confirmed. Thus, recent stroke may be not an absolute contraindication for HSCT.
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PMID:Nonmyeloablative allogeneic bone marrow transplantation for treatment of myelodysplastic syndrome complicated by recent intracerebral hemorrhage. 1555 6

Stroke causes brain injury in millions of people world wide each year. Despite the enormity of problem, currently there is no established therapy, which can restore the blood flow at infracted area and also improve the neurological deficit. The present study was carried out to investigate the effect of an endothelin antagonist (TAK-044) in middle cerebral artery (MCA) occlusion model of acute ischemic stroke in rats. Male Wistar rats were pretreated with TAK-044 (5 mg/kg, i.p.) for 7 days and thereafter subjected to focal ischemia by occlusion of MCA using intraluminal thread for two hours. 30 min after reperfusion the animals were subjected to diffusion-weighted imaging (DWI) for assessment of protective effect. Twenty-four hours later the motor performance was tested and subsequently the animals were sacrificed for estimation of markers of oxidative stress; malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). Control group received vehicle (saline) and similar experimental protocol was followed. In the TAK-044 pretreated group, percent hemispheric lesion area (% HLA) in DWI was significantly attenuated 17.5 +/- 0.5% as compared to control group 61.2 +/- 5.9%. Significant motor impairment, with significant elevated levels of MDA, decrease in GSH and SOD were observed in the vehicle treated MCA occluded rats. Pretreatment with TAK-044 prevented the motor impairment and significantly reversed the changes in markers of oxidative stress (MDA, GSH and SOD). In addition to well-known vasodilatory effect, TAK-044 has recently been documented to have antioxidant and anti-inflammatory properties. These effects can contribute to the protection afforded by TAK-044 in the present study.
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PMID:Effect of endothelin antagonist (TAK-044) on cerebral ischemic volume, oxidative stress markers and neurobehavioral parameters in the middle cerebral artery occlusion model of stroke in rats. 1584 15

Strong associations have been established between various HLA alleles and different complications of sickle cell disease (SCD). Recently, the HLA-DRB1*03 allele was shown to be associated with susceptibility to stroke while the HLA-DRB1*02 allele may be protective. While stroke and silent brain infarcts (SBI) are unusual in Kuwaiti children with SCD, avascular necrosis of the femoral head (AVNFH) is quite common. The modulatory association factors must still be elucidated. An investigation of HLA-DRB1 alleles was carried out in a group of 68 Kuwaiti SS patients, of age 7-44 years, of whom 20 (29.4%) had AVNFH, confirmed by magnetic resonance imaging. A group of 167 apparently healthy age- and sex-matched individuals served as controls. Comparison of the HLA alleles between the whole SS group and the controls showed a significant over-representation of DRB1*01 (P < 0.01) and DRB1*10 (P < 0.05) in the patient group. No significant differences in the allele frequencies in the SS patients with or without AVNFH were observed. It therefore appears that the HLA-DRB1 locus does not play a significant role in the pathogenesis of AVNFH Kuwaiti patients.
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PMID:HLA-DRB1 alleles in Hb SS patients with avascular necrosis of the femoral head. 1584 75

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only curative treatment for sickle cell disease (SCD); nevertheless, its use has been limited by the risk of transplantation-related mortality (TRM). Between November 1988 and December 2004, 87 consecutive patients with severe SCD ranging from 2 to 22 years of age received transplants in France. Cerebral vasculopathy was the principal indication for transplantation (55 patients). All the patients received grafts from a sibling donor after a myeloablative conditioning regimen (CR). The only change in the CR during the study period was the introduction of antithymocyte globulin (ATG) in March 1992. The rejection rate was 22.6% before the use of ATG but 3% thereafter. With a median follow-up of 6 years (range, 2.0 to 17.9 years), the overall and event-free survival (EFS) rates were 93.1% and 86.1%, respectively. Graft versus host disease (GVHD) was the main cause of TRM. Importantly, cord blood transplant recipients did not develop GVHD. No new ischemic lesions were detected after engraftment, and cerebral velocities were significantly reduced. The outcome improved significantly with time: the EFS rate among the 44 patients receiving transplants after January 2000 was 95.3%. These results indicate that HLA-identical sibling HSCT after myeloablative conditioning with ATG should be considered as a standard of care for SCD children who are at high risk for stroke.
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PMID:Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. 1822 76

UCBT was performed in seven children with SCD and stroke (HLA match 4/6 n=5; 5/6 n=2). Four received myeloablative regimens (BU, CY, ATG plus FLU in one patient). One had primary graft failure, three had sustained engraftment, two with grade III-IV GVHD (one died, one developed chronic GVHD), one with stable mixed chimerism. Three patients treated with reduced-intensity regimens (FLU, BU or CY, ATG, TLI) failed to engraft; one engrafted after second UCBT (HU, TT, RXA, ALZ, TBI). Four patients (57%) developed viral infections. Engraftment, GVHD, and infection remain challenges.
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PMID:Unrelated cord blood transplantation in children with sickle cell disease: review of four-center experience. 1766 78

Many patients with thalassemia have been cured with BMT since the first successful transplant in 1981. Allogeneic stem cell gene therapy is the only treatment option for patients with sickle cell anemia (SCA). A total of 11 patients with a median age of 12 years (range, 2-16), affected by SCA, received hematopoietic SCT from HLA-identical, related donors following a myeloablative-conditioning regimen. Indications for transplantation were vaso-occlusive crisis, acute chest syndrome, avascular bone necrosis, chronic RBC transfusions, or hemorrhagic stroke. All patients had sustained engraftment. One patient became a stable mixed chimera with 25% of donor cells at 4 years after transplantation. One patient died at 1 year after transplantation. The probability of survival, SCA-free survival and TRM at 5 years after transplant were 90, 90 and 10%, respectively. All 10 surviving patients remained free of any SCA-related events after transplantation. In conclusion, these data confirm SCT from a suitable HLA-matched, related donor should become the primary option for curing children with SCA. There is an excellent survival rate and a return to normal life, free of SCA-related events.
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PMID:Allogeneic cellular gene therapy in hemoglobinopathies--evaluation of hematopoietic SCT in sickle cell anemia. 2149 19


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