Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eleven adult patients with stable sickle cell disease (SCD) were investigated twice at a 15-day interval by nail fold capillaroscopy (NFC), bulbar conjunctival angioscopy (BCA), and laser Doppler flux metering (LDF). NFC and BCA are essentially descriptive. NFC revealed, in some patients, network patterns similar to those observed in vasculitis. BCA provides a reproducible method for the visual assessment of the microcirculation. When using a rating scale with five criteria it identified abnormalities related to both altered red blood cells and vascular morphology but failed to discriminate between patients. LDF, in contrast, is quantifiable and showed reproducible characteristic reactive alterations of vasomotion in response to ischemia after 3 min of occlusion. The SCD patients had a delayed response, best measured by the recovery half time, which was four to five times longer than that of normal subjects. In addition, the cold provocative test was always abnormal, as evidenced by a significant drop in the contralateral flux, and was often poorly tolerated. The observed trends suggest that BCA and LDF should be performed in a large cohort of patients, both in the steady state and during vasoocclusive crises. These methods seem to be useful complementary noninvasive procedures to cellular and clinical evaluation monitoring for therapeutic trials.
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PMID:Comparative evaluation of laser Doppler flux metering, bulbar conjunctival angioscopy, and nail fold capillaroscopy in sickle cell disease. 847 39

Patients with homozygous sickle cell disease pose an enormous challenge to the reconstructive surgeon. Historically, the risk of attempting flap reconstruction was considered prohibitive. A successful case of immediate breast reconstruction with a "supercharged" bipedicled transverse rectus abdominis musculocutaneous flap is presented. Perioperative transfusions that maintained the sickle hemoglobin S level below 30% were crucial in preventing erythrocyte sickling in the microcirculation of the flap during the period of relative ischemia.
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PMID:Transverse rectus abdominis musculocutaneous flap breast reconstruction in sickle cell disease. 857 70

Nitric oxide (NO) generated from L-arginine and molecular oxygen by nitric oxide synthase (NOS) has been shown to influence hepatocellular function and pathology in response to ischemia and certain hepatotoxins. In the present study, we examined the liver of a transgenic line of sickle cell mice for hepatocellular injury and localization of two isoforms of NOS, the endothelial constitutively expressed isoform (EcNOS) and the inducible isoform (iNOS) by immunohistochemistry. Diffuse expression of EcNOS was observed in hepatocytes of control and sickle cell animals maintained under room air conditions. In contrast, iNOS was observed only in the sickle cell mice, well-localized to hepatocytes surrounding the central veins of the lobules. When normal mice were exposed to hypoxic conditions for 4 to 5 days, iNOS immunostaining appeared de novo in a patchy distribution throughout the liver lobules. In the sickle cell mice, hypoxia appeared to increase the subjective intensity of pericentral staining of iNOS. Liver histology was normal in the sickle cell mice maintained under room air conditions, but showed multifocal areas of necrosis when sickling was exacerbated by chronic hypoxic conditions. However, a pericentral zone of preserved architecture was present, corresponding to the region of iNOS staining. We postulate that pericentral induction of iNOS under ambient conditions occurs in transgenic sickle cell mice in response to particularly intense hypoxic conditions near the central veins of the liver. Increases in NO synthesis may occur in this region, which would serve to protect these cells from ischemic damage either directly or by maintaining blood flow. These findings could be relevant to liver pathophysiology in patients with sickle cell disease.
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PMID:Immunohistochemical localization of hepatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia. 889 27

Patients with sickle cell disease may develop intracranial vascular disease, with the occlusion or obstruction of the large or small arteries, which may lead to the secondary development of moyamoya disease. In this report, we describe the neurochemical changes in the brain before, during, and after an extracranial-intracranial bypass procedure on a patient with sickle cell disease and a moyamoya disease like pattern on angiography. We used the in vivo microdialysis technique to measure the on-line pH, lactate and amino acid concentrations in the extracellular fluid. There were relatively high resting glutamate levels and a lower-than-normal pH in the extracellular fluid prior to the bypass, associated with chronic ischemia. During the bypass there was a short-lived increase in the glutamate levels. After revascularization, there was a rapid decrease in the glutamate levels and an increase in the pH value. The patient's preoperative neurological deficit improved post-operatively, corresponding to the biochemical changes towards normal values. These changes after revascularization suggest that chronic biochemical abnormalities due to brain ischemia may improve after cerebral revascularization.
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PMID:EC-IC bypass improves chronic ischemia in a patient with moyamoya disease secondary to sickle cell disease: an in vivo microdialysis study. 909 Jun 39

In red blood cells, a modulation of the level of the allosteric effector of hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) would have implications in the treatment of ischemia and sickle cell anemia. Its concentration is determined by the relative activities of the synthase and phosphatase reactions of the multifunctional bisphosphoglycerate mutase (BPGM). In this report we develop first a more direct synthase assay which uses glyceraldehyde phosphate to suppress the aldolase and triose phosphate isomerase reactions. Secondly we propose a radioactive phosphatase assay coupled to chromatographic separation and identification of the reaction products by paper electrophoresis. Such identification of these products allow us to show that the multifunctional BPGM expresses its mutase instead of its phosphatase activity in conditions of competition between the 3-phosphoglycerate and the 2-phosphoglycolate activator in the phosphatase reaction. These two more precise procedures could be used to study the effects of substrate and cofactor analogues regarding potential therapeutic approaches and could be used for clinical analyses to detect deficiency of BPGM.
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PMID:New procedures to measure synthase and phosphatase activities of bisphosphoglycerate mutase. Interest for development of therapeutic drugs. 909 61

Sickle-cell anemia is a congenital hemolytic anemia characterized by sickle-shaped RBCs. The deformed RBCs become distorted and rigid and may occlude small arterioles and capillaries leading to tissue ischemia and infarction. Sickled RBCs are too fragile to withstand the trauma of circulation, and hemolysis occurs after they enter the circulation. RBCs with a high level of Hb F are resistant to sickling. Hydroxyurea has been shown to stimulate Hb F synthesis, leading to a reduction in the incidence of hemolytic and vaso-occlusive manifestations; however, hydroxyurea has no role in the treatment of crises already in progress. The National Heart, Lung, and Blood Institute announced in January 1995 that treatment with hydroxyurea leads to an increase in Hb F production within RBCs and a reduction in the frequency of painful crises in patients with sickle-cell anemia. Although the mechanism by which hydroxyurea increases Hb F is not known, one possible explanation is that hydroxyurea is cytotoxic to the more rapidly dividing late erythroid precursors, leading to the recruitment of early erythroid precursors that have demonstrated increased capacities to produce Hb F. Clinical trials have demonstrated that hydroxyurea results in an increase in Hb F concentrations; however, this increase may not dramatically affect the progressive vascular changes associated with sickle-cell anemia; thus, patients may still experience complications related to sickle-cell anemia. At North Carolina Baptist Hospital in Winston-Salem, NC, compliant patients with sickle-cell anemia are started on hydroxyurea. There are no specific criteria for patient selection or monitoring. The dosage is started at 10-15 mg/kg/d. Platelet count, complete blood count, and Hb F are monitored and hydroxyurea dosages are adjusted accordingly. Although hydroxyurea has been effective in the treatment of sickle-cell anemia, large double-blind, placebo-controlled clinical trials are needed to determine whether the risks of long-term administration outweight the risk of vaso-occlusive disease in untreated patients.
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PMID:Hydroxyurea in the treatment of sickle-cell anemia. 939 97

The relative contributions of microvascular inflammation and vasomotor dysregulation to the development of acute vaso-occlusive crisis in sickle cell disease have been intensely studied. The present observational study was designed to examine the levels of circulating proinflammatory cytokines, anti-inflammatory cytokines, and vasoactive mediators during and after acute painful crisis. In symptomatic sickle cell patients, plasma levels of endothelin-1 and prostaglandin E2 were elevated during crises compared with healthy African-American controls. These levels had decreased, but not normalized, when patients were seen 1 to 3 weeks after discharge from hospital. Other mediators (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], IL-6, IL-8, and IL-10) were neither elevated in asymptomatic sickle cell disease nor in acute vaso-occlusive crisis. As a potent long-acting mediator of vasoconstriction and inflammation, endothelin-1 may play a key role in the cycle of ischemia and inflammation that initiates and sustains pain of crisis. The downregulatory effects of prostaglandin E2 on immune cell function may contribute to the increased susceptibility to infection observed in patients with sickle cell disease.
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PMID:Plasma endothelin-1, cytokine, and prostaglandin E2 levels in sickle cell disease and acute vaso-occlusive sickle crisis. 974 97

Children with sickle cell anemia (SS) have an increased risk for cerebral vasculopathy with stroke (CVA) and cognitive impairment. The present study examines the extent to which adding positron emission tomography (PET) to magnetic resonance imaging (MRI) can improve the detection of cerebral vasculopathy. Whereas MRI has been the prime modality for showing anatomical lesions, PET excels at assessing the functional metabolic state through glucose utilization 2-deoxy-2 [18F] fluoro-D-glucose (FDG) and microvascular blood flow ([15O]H2O). Forty-nine SS children were studied. Among them, 19 had clinically overt CVA, 20 had life-threatening hypoxic episodes or soft neurologic signs, and 10 were normal based on neurological history and examination. For the entire sample of 49 subjects, 30 (61%) had abnormal MRI findings, 36 (73%) had abnormal PET findings, and 44 (90%) showed abnormalities on either the MRI or the PET or both. Of the 19 subjects with overt CVA, 17 had abnormal MRI (89%), 17 had abnormal PET (89%), and 19 (100%) had either abnormal MRI or PET or both. Among the 20 subjects with soft neurologic signs, 10 (50%) had abnormal MRI, 13 (65%) had abnormal PET, and 17 (85%) had abnormal MRI and/or PET. Six (60%) of the 10 neurologically normal subjects had abnormal PET. Among the 30 subjects with no overt CVA, 25 (83%) demonstrated imaging abnormalities based on either MRI or PET or both, thus, silent ischemia. Lower than average full-scale intelligence quotient (FSIQ) was associated with either overt CVA or silent ischemic lesions. Four subjects who received chronic red blood cell transfusion showed improved metabolic and perfusion status on repeat PET scans. In conclusion, (1) the addition of PET to MRI identified a much greater proportion of SS children with neuroimaging abnormalities, particularly in those who had no history of overt neurologic events. (2) PET lesions are more extensive, often bihemispheric, as compared with MRI abnormalities. (3) PET may be useful in management as a tool to evaluate metabolic improvement after therapeutic interventions, and (4) the correlation of PET abnormalities to subsequent stroke or progressive neurologic dysfunction requires further study.
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PMID:Cerebral vasculopathy in sickle cell anemia: diagnostic contribution of positron emission tomography. 986 48

Cerebral vascular disease is a common and serious complication of sickle cell disease that mainly involves the large blood vessels of the skull base. Because recurrences are common and residual deficits severe, attention has turned to detection of preclinical cerebral involvement with the goal of preventing clinical damage. Magnetic resonance imaging (MRI), an extremely sensitive tool for detecting cerebral infarction/ischemia, has shown that 10% of asymptomatic patients exhibit white matter lesions that seem to be associated with impaired cognitive function and may be predictive of stroke; magnetic resonance angiography demonstrates occlusions of skull base arteries but is not reliable for the diagnosis of stenosis because of artifacts generated by rapid turbulent flow. Transcranial Doppler is sensitive and specific for the detection of arterial stenosis and occlusion, even in asymptomatic patients. Digitized cerebral angiography remains the gold standard investigation for pretreatment confirmation of lesions detected by Doppler and/or MRI.
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PMID:[Imaging of cerebrovascular disease in sickle cell anemia]. 1008 77

Plasmodium falciparum malaria, a parasitic disease, and sickle cell anemia, a hereditary disease, are two diseases affecting erythrocyte cycle, occurring with a high prevalence in tropical Africa. They may induce microthrombosis inducing vaso-occlusion, organ dysfunction and flap necrosis. During the acute phase of Plasmodium falciparum malaria, destruction of parasitized and healthy erythrocytes, release of parasite and erythrocyte material into the circulation, and secondary host reaction occur. Plasmodium falciparum infected erythrocytes also sequester in the microcirculation of vital organs and may interfere with microcirculatory flow in the flap during the postoperative period. The lower legs of homozygous sickle cell anemia patients are areas of marginal vascularity where minor abrasions become foci of inflammation. Inflammation results in decreased local oxygen tension, sickling of erythrocytes, increased blood viscosity and thrombosis with consequent ischemia, tissue breakdown and leg ulcer. Tissue transfer has become the procedure of choice for reconstruction of the lower third of the leg although flaps may become necrotic. The aim of this study is to analyse circumstances predisposing to surgical complications and to define preventive and therapeutic measures. A review of the literature will describe the current research and the new perspectives to treat sickle cell anemia, for example hydroxyurea and vasoactive substances (pentoxifylline, naftidrofuryl, buflomedil).
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PMID:[Falciform anemia and Plasmodium falciparum malaria: a threat to flap survival?]. 1018 98


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