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)

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A(2) (sPLA(2)), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA(2) predicts impending ACS. We prospectively evaluated sPLA(2) concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA(2) was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA(2) to 87% while retaining 100% sensitivity. These data indicate that sPLA(2) can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA(2) may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.
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PMID:Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease. 1105 14

The role of cytokines in the development of acute chest syndrome (ACS) in patients with sickle cell disease (SCD) was studied. Serum interleukin 8 (IL-8) levels were elevated in 14 episodes and undetectable in six out of 20 episodes of ACS in 19 patients with SCD. In contrast, IL-8 levels were undetectable in the sera of 29 control patients with SCD studied during routine clinic visits or hospitalization for vaso-occlusive crises. The differences in mean IL-8 levels and the proportion of patients with detectable levels between the two groups were highly significant (P < 0.0001 and 0.04 respectively). The mean IL-8 level in bronchial fluid samples from children with ACS was also significantly higher than that in sickle cell patients undergoing elective surgery (5500 +/- 1400 pg/ml vs. 1900 +/- 470 pg/ml, P = 0.03). Granulocyte colony-stimulating factor (G-CSF) (2000 +/- 1700 pg/ml) was present in five out of six samples of bronchial fluid, but not serum, from children with ACS. All but one of the patients with ACS studied were negative for the Duffy red cell antigen, which is a receptor that binds and inactivates IL-8 and other chemokines. These findings suggest that IL-8 and G-CSF may play a role in the development of the ACS and the complications associated with it.
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PMID:Elevated serum and bronchoalveolar lavage fluid levels of interleukin 8 and granulocyte colony-stimulating factor associated with the acute chest syndrome in patients with sickle cell disease. 1112 88

The pulmonary findings of acute chest syndrome of sickle cell disease have been well characterized in numerous studies. Whereas a third of patients have a documented infection associated with this syndrome, and fat embolism from necrotic marrow is the etiologic factor in another approximately 10%, no cause is discovered in the majority of patients. In most patients, however, the underlying pathophysiology is the presence of a hypoxia-driven, adhesion-related occlusive event in the pulmonary microcirculation. This may be accompanied by a decrease in the levels of normal cytoprotective and anti-adhesive mediators such as nitric oxide. In the patient with sickle cell disease, the lung is also a uniquely vulnerable target organ because its vasculature constricts with hypoxia in contrast to other vascular beds. This review will establish the links between known etiologic agents and the pathophysiology of this syndrome. An additional section of this review will deal with experimental therapies. The use of inhaled nitric oxide will be explored in depth because advances in this area are current and uniquely relevant to acute chest syndrome.
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PMID:Acute chest syndrome of sickle cell disease: new light on an old problem. 1122 86

Cholecystectomy is a common surgical procedure performed in patients with sickle cell disease (SCD). Postoperative complications, including acute painful vaso-occlusive crisis and acute chest syndrome, have been described frequently after either traditional or laparoscopic cholecystectomy (LC). It's still not clear if preoperative blood transfusion, hyperhydration, intraoperative body temperature conservation may reduce complications rate. The Authors reviewed the charts of seven patients with SCD operated on LC for symptomatic gallbladder lithiasis and describe their perioperative management. In 3 patients preoperative endoscopic removal of stones was achieved. Five patients with HB lower than 9 g/dl and/or HbS higher than 40% were transfused preoperatively and all the patients were hyperhydrated. Intraoperative monitoring was achieved for early recognition of ventilation to perfusion mismatch and acid-base balance or temperature modifications. The Authors reported only one case of postoperative lower extremities pain. This study suggests that LC is a safe procedure in SCD if appropriate monitoring and perioperative management are achieved.
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PMID:Laparoscopic cholecystectomy in adult patients with sickle cell disease. 1127 37

While the problem of stroke in the patients with sickle cell disease (SCD) has been known for more than 75 years, adequate preventive and treatment strategies are just now being tested. Recent data on prevalence and incidence have been obtained from the Cooperative Study of Sickle Cell Disease of more than 4000 patients with SCD observed in 23 US clinical centers over a 10-year period.1 The overall age-specific incidence of first stroke in SCD (homozygous sickle cell anemia) is low (0.13%) at ages younger than 24 months, increasing to just over 1% at ages 2 to 5 years, with only a slight decrement to 0.79% at ages 6 to 9 years. The risk of brain infarction declines until a second peak is seen at ages older than 50 years, when the incidence again increases to nearly 1.3%. Although intracranial hemorrhage does occur in young children with SCD, the risk is low compared with older children and adults. The Cooperative Study of Sickle Cell Disease reported risk factors for infarction to be prior transient ischemic attack, low steady-state hemoglobin values, and rate and recency of episodes of acute chest syndrome, as well as elevated systolic blood pressure. Risk factors for intracranial hemorrhage included low steady-state hemoglobin values and a high leukocyte count. The burden of cerebrovascular disease is even higher if subclinical magnetic resonance imaging (MRI) lesions, presumed to be ischemic, are included. The prevalence of such lesions is more than 22% in patients with SCD, and most of these patients have not reported symptoms, although specialized neuropsychological testing shows lower scores in children with silent lesions on MRI scans. Patients with a history of clinical stroke typically have infarcts in the cortex and deep white matter, whereas silent infarcts tend to be more limited to deep white matter. Common infarction patterns are characterized by wedge-shaped lesions of large-vessel territories; border zone infarctions, particularly of the middle and cerebral artery watershed region; and small punctate lesions of the deep white matter. Fat embolism to the brain and venous thromboses are encountered rarely.
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PMID:Stroke prevention and treatment in sickle cell disease. 1129 86

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P =.0002) and days in the hospital (P <.01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support. (Blood. 2001;97:3628-3632)
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PMID:Five years of experience with hydroxyurea in children and young adults with sickle cell disease. 1209 15

The relationship between each of haemoglobin concentration (Hb), red cell count (RCC), white cell count (WBC), platelet count (PLT), mean corpuscular volume (MCV), red cell width difference (RWD), and average number of acute admissions per year (AVEADM), were determined in a cross-sectional study of 128 Afro-Caribbean sickle cell anaemia patients attending the Sickle Cell Disease Clinic of Central Middlesex Hospital in London for a mean of 7.6 patient-years. The diagnosis of sickle cell anaemia was made by both haematological and DNA analyses. The haematological parameters were determined using Coulter S automated counter during the steady state periods while the AVEADM was computed from all admissions for painful crisis, acute anaemia and acute chest syndrome, priapism, and acute stroke. Haemoglobin F level was determined by HPLC. Analysis was done in the paediatric and adult patients separately. There were no significant correlations between any of the parameters and AVEADM in the paediatric group. In adult patients, there was significant positive correlation (P < 0.05) between WBC and AVEADM. WBC has a negative correlation with Hb concentration and HbF level. WBC 10 x 10(9)/L and above is associated with Hb and HbF level below the mean for the group. WBC is lower but not significantly, in patients with single alpha-gene deletion than in those without deletion (P = 0.06). This study suggests that higher WBC count may suggest possible increased hospital admission, lower Hb concentration, and lower HbF level, in adult patients, and that, as a single parameter it can be of value in the assessment of patients with sickle cell anaemia. Possible mechanisms for these findings are also suggested.
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PMID:The predictive value of white cell count in assessing clinical severity of sickle cell anaemia in Afro-Caribbeans patients. 1137 63

Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes. Studies demonstrating a beneficial effect of steroid therapy for painful episodes and acute chest syndrome provide indirect evidence for the role of inflammation in this disease. Leukocytosis, in the absence of infection, is common in SCD patients and predicts for stroke, acute chest syndrome, and overall mortality. Neutrophils and monocytes have been shown to be activated in these patients. Activated leukocytes further promote vascular inflammation and vessel damage. A reduction in leukocytes, and thus inflammation, may partially explain the beneficial effects of hydroxyurea in this disease. These data provide a strong rationale for clinical studies of therapy directed at inflammation and/or leukocytes in sickle cell disease.
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PMID:The Role of Inflammation and Leukocytes in the Pathogenesis of Sickle Cell Disease; Haemoglobinopathy. 1139 40

Cerebral infarction is a frequent, severe complication of sickle cell anaemia. During childhood, most strokes are due to infarction with the majority resulting from occlusion of the large cerebral arteries. Risk factors include transient ischaemic attacks, acute chest syndrome, severe anaemia and elevated blood pressure. Less certain is the association with leucocytosis, or protection provided by alpha-thalassaemia or fetal haemoglobin. Children who have one stroke are at significant risk for having subsequent events that can be substantially reduced by maintaining haemoglobin S below 30%. It has not yet been possible to identify individuals for whom transfusion can be safely stopped. Haemosiderosis is a consequence of intensive and long term transfusion therapy, which requires chelation with deferoxamine. Iron accumulation can be minimised using erythrocytapheresis but this is technically difficult in children, expensive and results in increased donor exposure. In addition to lesions associated with strokes, an additional 17% of patients can be shown to have clinically silent cerebral infarcts. Although these are termed 'silent', those affected have mild neuropsychological deficits. Their relationship to stroke or risk for recurrence is unknown. Transfusion therapy has been shown to provide primary stroke prevention for children who have elevated cerebral artery velocity. Finally, intracranial haemorrhages, more commonly found in adults, also affect children. Subarachnoid haemorrhage is frequently found to result from cerebral artery aneurysms. A condition that mimics the moyamoya syndrome radiographically, as well as for its risk of haemorrhage, can be found in children with partly occluded cerebral arteries either as a result of stroke or silent infarct.
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PMID:Stroke in children with sickle cell anaemia: aetiology and treatment. 1143 87

Acute chest syndrome is a major cause of death and hospitalisation in children with sickle cell anaemia. It is often initiated by an infection, particularly pneumonia. Microbial agents previously not associated with acute chest syndrome are becoming increasingly important. Group A beta-haemolytic Streptococcus (GABHS) is thought to be an uncommon cause of pneumonia in children with sickle cell anaemia. We report a 15-year-old African-American girl who presented with an acute chest event characterised by fever, cough, chest pain, shortness of breath, right upper abdominal quadrant pain, jaundice and otitis media. Chest radiograph showed multi-lobar pneumonia with left pleural effusion. Group A beta-haemolytic Streptococcus was isolated from culture of pleural and middle ear fluids. She responded to therapy that included antibiotics, exchange blood transfusion, oxygen, thoracotomy chest tube drainage and decortication. In a child with sickle cell anaemia presenting with fever and an acute chest event, pneumonia should be considered and GABHS recognised as a possible aetiological agent. In addition, a chest X-ray should be obtained and antibiotics against agents causing community-acquired pneumonia instituted.
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PMID:Group A beta-haemolytic streptococcal acute chest event in a child with sickle cell anaemia. 1147 Dec 64


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