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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent clinical and experimental data suggest that nitric oxide (NO) may play a role in the pathogenesis and therapy of sickle cell disease. NO, a soluble gas continuously synthesized in endothelial cells by the NO synthase (NOS) enzyme systems, regulates basal vascular tone and endothelial function, and maintains blood oxygenation via hypoxic pulmonary vasoconstriction and reduced shunt physiology. These vital homeostatic processes may be impaired in sickle cell disease and contribute to its pathogenesis. Therapeutic NO inhalation exerts significant direct effects on the pulmonary vasculature to reduce pulmonary pressures and increase oxygenation that may prove beneficial in acute chest syndrome and secondary pulmonary hypertension. Delivery of NO bound to hemoglobin or in plasma may improve blood flow and hemoglobin saturation, and thus reduce ischemia-reperfusion injury. Other NO-related effects on adhesion molecule expression and fetal hemoglobin induction are of interest. While direct evidence for a clinical benefit of NO therapy in sickle cell disease has not been reported, studies are underway to determine if inhaled NO will reduce the substantial morbidity and mortality suffered by these patients.
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PMID:Nitric oxide therapy in sickle cell disease. 1160 68

Endomyocardial biopsies of patients with sickle cell anemia (SCA) were examined ultrastructurally. Myocardial fibers of patients revealed prominent degenerative changes such as nuclear chromatin condensation, myofibrillar degeneration, sarcosomal changes, dilatation of sarcoplasmic reticulum, formation of autophagic vacuoles, increase of lipofuscin granules and occurrence of vacuoles derived from endoplasmic reticulum and/or transverse tubules in some micrographs. Furthermore, edematous changes were developed at the same area where the degenerative changes were prominent. All of these cellular alterations could be related with ischemia resulting from local microvascular occlusion.
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PMID:Ultrastructural alterations in the myocardium of patients with sickle cell anemia. 1168 96

Sickle cell disease is the most common and severe hemoglobinopathy. Ocular complications are related to ischemic retinopathy. Retinal examination has to be done in homozygous or double heterozygous patients and when the sickle trait is present with additional systemic vascular conditions. Fluorescein angiography is the main investigation. Photocoagulation to ischemic areas is effective in achieving regression of neovascularization. Various measures to reduce ischemia are recommended for surgical procedure. Multidisciplinary teams should take on severe cases.
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PMID:[Retinal involvement in hemoglobinopathy]. 1191 46

The role of plasma-phase risk factors for stroke in the pediatric age group is presently unclear due to the lack of sufficiently large prospective studies, and due to the fact that these risk factors do not apply uniformly to newborns, children with sickle cell disease, and older children. Available evidence indicates that factor V Leiden, prothrombin 20210A, and lipoprotein (a) are all important in the pathogenesis of arterial ischemic stroke in older children, but the role of other plasma-phase risk factors remains uncertain. The contribution of these risk factors to newborn stroke and the stroke of children with sickle cell disease is similarly unclear, likely because the ischemia in affected children is predominantly due to nonhematologic perinatal events and erythrocyte adhesion to endothelium with obstruction of flow in the cerebral microcirculation, respectively. Evaluation of childhood stroke should, in our view, always be performed from the standpoint of the presenting clinical symptoms, diagnostic imaging, and determination of plasma-phase risk factors. Therapeutic anticoagulation and use of antiplatelet agents at present focus on the older child.
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PMID:Arterial ischemic stroke in childhood: the role of plasma-phase risk factors. 1192 26

Peripheral retinal neovascularization occurs in approximately 10% of cases of sarcoidosis. Its pathogenesis is unknown, but it probably results from retinal ischemia and/or inflammation. In cases of peripheral retinal neovascularization associated with sarcoidosis, sickle cell disease should be considered, even if sarcoidosis is histologically proved: new vessels seen in sickle cell disease and sarcoidosis may have a very similar pattern. We present two cases with histologically proven sarcoidosis who developed peripheral neovascularization: the first one had no associated disease and new vessels were likely to be related to sarcoidosis; in the second case, hemoglobin electrophoresis revealed hemoglobin SC, and provided diagnosis of sickle cell hemoglobinopathy.
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PMID:[Peripheral retinal neovascularization and sarcoidosis: two case reports]. 1194 Dec 57

The intermittent vascular occlusion occurring in sickle cell disease (SCD) leads to ischemia-reperfusion injury and activation of inflammatory processes including enhanced production of reactive oxygen species and increased expression of inducible nitric-oxide synthase (NOS2). Appreciating that impaired nitric oxide-dependent vascular function and the concomitant formation of oxidizing and nitrating species occur in concert with increased rates of tissue reactive oxygen species production, liver and kidney NOS2 expression, tissue 3-nitrotyrosine (NO(2)Tyr) formation and apoptosis were evaluated in human SCD tissues and a murine model of SCD. Liver and kidney NOS2 expression and NO(2)Tyr immunoreactivity were significantly increased in SCD mice and humans, but not in nondiseased tissues. TdT-mediated nick end-label (TUNEL) staining showed apoptotic cells in regions expressing elevated levels of NOS2 and NO(2)Tyr in all SCD tissues. Gas chromatography mass spectrometry analysis revealed increased plasma protein NO(2)Tyr content and increased levels of hepatic and renal protein NO(2)Tyr derivatives in SCD (21.4 +/- 2.6 and 37.5 +/- 7.8 ng/mg) versus wild type mice (8.2 +/- 2.2 and 10 +/- 1.2 ng/mg), respectively. Western blot analysis and immunoprecipitation of SCD mouse liver and kidney proteins revealed one principal NO(2)Tyr-containing protein of 42 kDa, compared with controls. Enzymatic in-gel digestion and MALDI-TOF mass spectrometry identified this nitrated protein as actin. Electrospray ionization and fragment analysis by tandem mass spectrometry revealed that 3 of 15 actin tyrosine residues are nitrated (Tyr(91), Tyr(198), and Tyr(240)) at positions that significantly modify actin assembly. Confocal microscopy of SCD human and mouse tissues revealed that nitration led to morphologically distinct disorganization of filamentous actin. In aggregate, we have observed that the hemoglobin point mutation of sickle cell disease that mediates hemoglobin polymerization defects is translated, via inflammatory oxidant reactions, into defective cytoskeletal polymerization.
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PMID:Nitric oxide-dependent generation of reactive species in sickle cell disease. Actin tyrosine induces defective cytoskeletal polymerization. 1240 83

We report a case of an adolescent who had sickle cell disease and previous evidence of myocardial damage and presented with abdominal pain and rapid progression to cardiogenic shock and subsequent development of myocardial infarction. To our knowledge, this represents only the second report of a case of acute myocardial ischemia and subsequent infarction resulting transient ventricular dysfunction reported in a child with sickle cell disease successfully treated with exchange transfusion. The pathophysiology of this complication remains unclear, and cardiac complications may remain undetected as lung, bone, and brain infarcts are more common and the pain associated with sickle cell crisis may mask the ischemic symptoms. Multiple factors may contribute to ischemia in addition to the presence of a vaso-occlusive crisis or infection. Acute or chronic myocardial ischemia are probably more prevalent than currently known.
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PMID:Myocardial infarction and transient ventricular dysfunction in an adolescent with sickle cell disease. 1256 93

Hepatomegaly and alterations in hepatic function are common to all patients with sickle-cell disease. In these patients, hepatic sickling is a manifestation of severe intrahepatic vaso-oclusive crises, even at levels of 25 % HbS and hematocrits of more than 45-50 %, which in 10 % of cases can lead to acute hepatic failure (AHF). AHF can be due to a variety of causes, including hematologic malignancies, but T cell lymphoma, which is usually secondary to diffuse hepatic infiltration and ischemia, is an exceptional cause, although other mechanisms can be involved. Cytokines released by lymphomas have recently been implicated as a cause of AHF.We describe a black girl with sickle cell disease, who developed AHF due to T cell lymphoma without lymphomatous infiltration of the liver. The only mechanism found to explain the clinical findings was release of cytokines by lymphoma. In patients with AHF of unknown etiology we propose early liver biopsy, because prognosis depends on the presence or absence of hepatic tumour infiltration. If AHF develops in a patient with diagnosed malignant disease, cytokine release may be the cause of AHF. Consequently, early diagnosis of the underlying disease and provision of liver support, as well as direct removal of inflammatory mediators from the circulation by exchange transfusion or other methods, should be the main priorities.
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PMID:[Acute liver failure due to T cell lymphoma without hepatic infiltration]. 1262 21

Sickle cell disease (SCD) is one of the most common inherited diseases worldwide. The disease is characterized by chronic hemolytic anemia, as well as acute and chronic complications. One of the most intractable problems encountered by children with SCD is the painful episode that results from tissue ischemia due to vaso-occlusion. Pain related to SCD is unique among pain syndromes due to the unpredictable, recurrent, and often persistent nature of the disease, as well as the recurring and essential need for the use of opioids. Painful vaso-occlusive episodes (VOE) are a principal cause of morbidity and account for a significant number of emergency department and hospital admissions. When untreated or inadequately managed, the pain of VOE may cause both short- and long-term consequences. Despite the fact that pain is an almost universal feature of the disease, children with SCD may form one of the most undertreated and understudied populations. One of the factors contributing to poor pain management is conflicting perceptions between patients, their families, and healthcare professionals about pain that is reported and analgesia that is required. Pain management guidelines have recently been published in an effort to overcome barriers in the assessment and management of pain related to SCD. Although there is considerable variability in the way SCD pain is managed, the standard treatment protocol for painful episodes has been rest, rehydration, and analgesia. However, pain control for children with SCD is often a difficult and complex process, and one that requires frequent systematic pain assessments and continuous adjustment of comfort measures, especially analgesics. There are a variety of analgesic agents to choose from, such as acetaminophen (paracetamol), oral or parenteral nonsteroidal anti-inflammatory drugs, and oral or parenteral opioids. Each of these options has advantages and disadvantages to their use. Continuous infusions of analgesics and patient controlled analgesia have been shown to be effective and widely used in hospital settings to manage severe pain. However, the opioid dose required to achieve pain relief varies considerably within each painful episode, from one episode to another, and between individual patients. Although not yet curable in humans, pain related to SCD can be effectively managed in most patients by using a comprehensive approach that incorporates pharmacologic, psychologic, behavioral, and physical pain management strategies.
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PMID:Pain management in children with sickle cell disease. 1266 19

Osteonecrosis is a clinical entity characterized by death of bone marrow and trabecular bone as a result of disruption of blood supply to the bone (1,2). Other aspects of this condition include avascular necrosis, aseptic necrosis, and osseous ischemic necrosis of bones. Osteonecrosis is classified into two main forms; post-traumatic and nontraumatic. The post-traumatic form of osteonecrosis usually develops as a result of traumatic displacement of bone fragments, which leads to impaired blood supply and ischemia to the affected bone. Osteonecrosis of the femoral head is common following fracture of the femoral neck. A variety of systemic diseases and clinical conditions are associated with nontraumatic osteonecrosis. These include autoimmune rheumatic diseases, alcoholism, pregnancy, Gaucher's disease, thrombophilia, corticosteroid therapy, Sickle-cell anemia, pancreatitis, inflammatory bowel diseases, and use of cytotoxic drugs and others. Idiopathic forms of osteonecrosis have also been reported (2-4). Among the rheumatic diseases, osteonecrosis is strongly associated with systemic lupus erythematosus (SLE) (5). However, osteonecrosis has been diagnosed in patients with primary antiphospholipid syndrome (APS) (6), rheumatoid arthritis (7), and systemic vasculitis (8). This article reviews the causes, clinical and epidemiological features, diagnosis, and treatment options for osteonecrosis among patients with SLE.
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PMID:Osteonecrosis in patients with SLE. 1279 57


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