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

Rapid recognition of acute chest syndrome is essential in patients with sickle cell disease. The condition can be particularly severe in adolescents and adults and often leads to death. In this article, the authors review the challenges of evaluating the syndrome and outline current treatment and supportive care.
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PMID:Acute chest syndrome in sickle cell disease. Crucial considerations in adolescents and adults. 1064 75

Fifty children who had symptomatic sickle cell disease received matched sibling marrow allografts between September 1991 and March 1999, with Kaplan-Meier probabilities of survival and event-free survival of 94% and 84%, respectively. Twenty-six patients (16 male, 10 female) had at least 2 years of follow-up after transplantation and were evaluated for late effects of transplantation and for its impact on sickle cell-related central nervous system (CNS) and pulmonary disease. Patients ranged between 3.3 and 14.0 (median, 9. 4) years of age and had a median follow-up of 57.9 (range 38-95) months after transplantation. Among 22 of 26 patients who had stable donor engraftment, complications related to sickle cell disease resolved, and none experienced further episodes of pain, stroke, or acute chest syndrome. All 10 engrafted patients with a prior history of stroke had stable or improved cerebral magnetic resonance imaging results. Pulmonary function tests were stable in 22 of the 26 patients, worse in two, and not studied in two. Seven of eight patients transplanted for recurrent acute chest syndrome had stable pulmonary function. Linear growth measured by median height standard deviation score improved from -0.7 before transplantation to -0.2 after transplantation. An adverse effect of busulfan conditioning on ovarian function was demonstrated in five of seven evaluable females who are currently at least 13 years of age. None of the four males tested had elevated serum gonadotropin levels. These data confirm that allogenic bone marrow transplantation establishes normal erythropoiesis and is associated with improved growth and stable CNS imaging and pulmonary function in most patients. (Blood. 2000;95:1918-1924)
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PMID:Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. 1070 55

Sickle cell disease is caused by a variant of the beta-globin gene called sickle hemoglobin (Hb S). Inherited autosomal recessively, either two copies of Hb S or one copy of Hb S plus another beta-globin variant (such as Hb C) are required for disease expression. Hb S carriers are protected from malaria infection, and this protection probably led to the high frequency of Hb S in individuals of African and Mediterranean ancestry. Despite this advantage, individuals with sickle cell disease exhibit significant morbidity and mortality. Symptoms include chronic anemia, acute chest syndrome, stroke, splenic and renal dysfunction, pain crises, and susceptibility to bacterial infections. Pediatric mortality is primarily due to bacterial infection and stroke. In adults, specific causes of mortality are more varied, but individuals with more symptomatic disease may exhibit early mortality. Disease expression is variable and is modified by several factors, the most influential being genotype. Other factors include beta-globin cluster haplotypes, alpha-globin gene number, and fetal hemoglobin expression. In recent years, newborn screening, better medical care, parent education, and penicillin prophylaxis have successfully reduced morbidity and mortality due to Hb S.
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PMID:Sickle hemoglobin (HbS) allele and sickle cell disease: a HuGE review. 1079 57

Acute chest syndrome (ACS) is an acute pulmonic process in patients with sickle cell disease. We prospectively studied 50 patients with ACS admitted to the Pediatric Medical Ward during one year period (Jan. 1993 through Dec. 1993). Twenty eight of them were males and twenty two were females giving a male: female ratio of 1.2:1. The age ranged between one and 12 years. Twelve (24%) of the patients had chest pain on presentation. Twenty seven (54%) patients had significant temperature (> 38 degrees C). The x-ray findings showed that the right lung was involved in 30 patients, the left in 10 patients and both lungs in 10 patients. Three patients had pleural effusion that required chest tube insertion. Laboratory profiles showed that the erythrocyte sedimentation rate ranged between 15 and 90 mm/h, and their hemoglobin ranged between 4.2 gm and 12 gm/dl. Seven (14%) patients had significantly positive mycoplasma pneumoniae titer. None of the blood cultures was positive. All of our patient received antibiotic, usually either Cefuroxime or Ceftriaxone with Erythromycin in addition to other supportive measures such as blood transfusion, oxygen therapy and hydration therapy.
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PMID:Acute chest syndrome in children with sickle cell disease. 1082 68

Clinical, molecular, and genetic advances have revealed new pathophysiologic insights and treatments for the growing number of recognized hematologic and nonhematologic abnormalities in sickle cell disease. Treatment targets of cellular dehydration, sickle hemoglobin concentrations, endothelial dysfunction, and abnormal coagulation regulation have been validated as potential therapy. New uses for transfusion therapy hold the promise of decreased major symptoms of acute chest syndrome, stroke, and severe pain crises, but at the expense of increased risk for transfusion reactions, infections, and iron overload. Accumulated experience with autologous, chimeric, and stem cell bone marrow transplantation holds promise for a small percentage of patients with disease. Patient selection, suitable donors, and early mortality are still limiting factors. Genetic manipulation, which offers hope for ameliorating the disease in a larger percentage of patients, is progressing slowly. Combination and staged therapies will be developed and matched to the severity and progression of the patient's disease. Strategies for prevention of major organ damage to the brain, heart, lungs, and kidneys will be prospectively evaluated and refined.
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PMID:Major changes in sickle cell disease. 1095 46

Over the past 25 years, morbidity and mortality have decreased significantly in children with sickle cell disease, and screening tests are now available to diagnose the disease in newborns. The incidence of sepsis caused by pneumococcal and Haemophilus influenzae infections has declined because of the prophylactic administration of penicillin soon after birth and the timely administration of pneumococcal and H. influenzae type b vaccines. Optimal nutrition can maximize growth in children with sickle cell disease, and timely screening can identify complications such as retinal damage and chronic renal involvement, thereby ensuring prompt treatment. Family physicians and parents who have been educated about sickle cell disease can detect acute, life-threatening complications such as splenic sequestration crisis and acute chest syndrome at their onset, thereby allowing treatment to be instituted without delay.
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PMID:Sickle cell disease in childhood: Part I. Laboratory diagnosis, pathophysiology and health maintenance. 1099 28

Augmentation of the fetal hemoglobin (HbF) levels is of therapeutic benefit in patients with sickle cell anemia. Hydroxyurea (HU), by increasing HbF, lowers rates of pain crisis, episodes of acute chest syndrome, and requirements for blood transfusions. For patients with no HbF elevation after HU treatment, augmentation of HbF levels by 5-aza-2'-deoxycytidine (5-aza-CdR, decitabine) could serve as an alternate mode of treatment. Eight adult patients participated in a dose-escalating phase I/II study with 5-aza-CdR at doses ranging from 0.15 to 0.30 mg/kg given 5 days a week for 2 weeks. HbF, F cell, F/F cell, gamma-globin synthesis ratio, complete blood count, and chemistry were measured. The average gamma-globin synthesis relative to non-alpha-globin synthesis prior to therapy was 3.19% +/- 1.43% and increased to 13.66% +/- 4.35% after treatment. HbF increased from 3.55% +/- 2.47% to 13.45% +/- 3.69%. F cells increased from 21% +/- 14.8% to 55% +/- 13.5% and HbF/F cell increased from 17% to 24%. In the HU nonresponders HbF levels increased from 2.28% +/- 1.61% to 2.6% +/- 2.15% on HU, whereas on 5-aza-CdR HbF increased to 12.70% +/- 1.81%. Total hemoglobin increased by 1 g/dL in 6 of 8 patients with only minor reversible toxicities, and all patients tolerated the drug. Maximum HbF was attained within 4 weeks of treatment and persisted for 2 weeks before falling below 90% of the maximum. Therefore 5-aza-CdR could be effective in increasing HbF in patients with sickle cell anemia who failed to increase HbF with HU. Demonstration of sustained F levels with additional treatment cycles without toxicity is currently being performed.
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PMID:2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. 1100 87

A subset of 299 patients with homozygous sickle cell anaemia, enrolled in the cohort of the French Study Group on sickle cell disease (SCD), was investigated in this study. The majority of patients were children (mean age 10.1 +/- 5.8 yr) of first generation immigrants from Western and Central Africa, the others originated from the French West Indies (20.2%). We report the frequency of the main clinical events (mean follow-up 4.2 +/- 2.2 yr). The prevalence of meningitis-septicaemia and osteomyelitis was, respectively, 11.4% and 12% acute chest syndrome was observed in 134 patients (44.8%). Twenty patients (6.7%) developed stroke with peak prevalence at 10-15 yr of age. One hundred and seventy-two patients (58%) suffered from one or more painful sickle cell crises, while the others (42.5%) never suffered from pain. The overall frequency of acute anaemic episodes was 50.5%, (acute aplastic anaemia 46%; acute splenic sequestration 26%). A group of 27 patients were asymptomatic (follow-up > 3 yr). Epistatic mechanisms influencing SCD were studied. Coinherited alpha-thalassemia strongly reduced the risk of stroke (p <0.001) and increased that of painful crises (p < 0.02). There was a low prevalence of Senegal and Bantu (CAR) betas-chromosomes in patients with meningitis (p <0.04) and osteomyelitis (p < 0.03). Prevalence of Senegal betas-chromosomes was lower in the asymptomatic group of 27 patients (p < 0.02). The patients come from a population of unmixed immigrants in whom the beta-globin gene haplotype strongly reflects the geographic origin and identifies subgroups with a homogenous genetic background. Thus the observed effects might result more from differences in as yet unidentified determinants in the genetic background than from the direct linkage with differences in the beta-globin gene locus.
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PMID:Acute clinical events in 299 homozygous sickle cell patients living in France. French Study Group on Sickle Cell Disease. 1100 50

Treatment advances over the past 25 years have significantly decreased morbidity and mortality in children with sickle cell disease. Aggressive management of fever, early diagnosis of acute chest syndrome, judicious use of transfusions and proper treatment of pain can improve quality of life and prognosis for these children. Prophylactic hydroxyurea therapy has been shown to reduce the incidence and severity of pain crises in adults with sickle cell disease and has been effective in limited studies conducted in children. Research into stem cell transplantation provides hope that a cure for sickle cell disease may be possible.
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PMID:Sickle cell disease in childhood: Part II. Diagnosis and treatment of major complications and recent advances in treatment. 1101 59

We report various pulmonary complications occurring in 88 patients with sickle cell disease: 44 Hb SS, 29 Hb Sb and 15 Hb SC. Pulmonary infections were observed in 20% of patients, and initiated the disease in 7% of cases. They were common in children younger than 10 years especially in Hb SS and Hb Sb patients. Bacteria were identified in 50% of cases predominantly S. pneumoniae, Mycoplasma pneumoniae, and Haemophilus influenzae. Acute chest syndrome occurred in adolescents and adults and was the consequence of pulmonary infarct or embolism which should be differentiated from bacterial pneumonia. Restrive syndrome was present in 2/3 of patients. It was associated to hypoxemia in 80% of cases. Prophylactic therapy was of paramount importance on long-term penicillin therapy and on closely-spaced immunization against pneumococci and Haemophilus influenzae. Blood exchange are indicated in severe hypoxemia.
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PMID:[Pulmonary complications in sickle cell syndromes]. 1102 21


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