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)

We evaluated the utility of the PFA-100 platelet function analyzer in identifying disorders in platelet function and/or von Willebrand factor (vWF) in patients with various systemic disorders being followed at a tertiary care center. Closure times were determined with collagen/ ADP (CADP) and collagen/epinephrine (CEPI) cartridges for 305 patients, and abnormal results were further evaluated with platelet aggregometry and vWF analysis. Prolonged CADP and/or CEPI closure times were identified in 114 patients (37.3%), but most were isolated prolonged CEPI closure times predominantly due to aspirin therapy (79 patients). Prolonged CADP closure times were most frequently due to qualitative platelet defects and/or decreased vWF levels. Prolonged CADP closure times were encountered most frequently in patients with sickle cell disease and were associated with a decreased hematocrit. This study demonstrated that the PFA-100 analyzer can accurately assess vWF-dependent platelet function and detect other platelet defects under high shear stress in complex patient populations.
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PMID:Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center. 1092 77

Growth and skeletal maturation are impaired in sickle cell disease (SCD). SCD is also associated with decreased bone mineral density (BMD) as determined by dual X-ray and photon absorptiometry. Quantitative ultrasound (US), which is as good a predictor of fracture as absorptiometry, provides additional information about bone architecture and elasticity. It is not known if the quantitative US parameters, broadband ultrasound attenuation (BUA) and speed of sound (SOS), are affected in children and adolescents with SCD. We therefore compared the bones of 80 children with SCD in Nigeria to those of age- and gender-matched controls using calcaneal ultrasound and the serum bone markers N-telopeptide of type1 collagen (NTx) and bone-specific alkaline phosphatase (BSAP), which are indicators of bone resorption and formation, respectively. BUA, which is reflective of BMD, was significantly lower for both the male and female SCD subjects compared with controls (86 vs 113 dB/MHz, P < 0.001 and 87 vs 100 dB/MHz, P < 0.001, respectively). However, SOS, which is more indicative of bone elasticity, was significantly different only for the male SCD subjects. Both NTx and BSAP were significantly reduced in the serum of the male and female SCD subjects. Correlations between BUA and serum NTx were found for both female controls and SCD subjects (r = 0.58, P < 0.001 and r = 0.32, P = 0.05, respectively), but not for the male subjects or controls. Significant correlations between BUA and BSAP were observed only for the female controls. In summary, we have shown that US analysis, in combination with serum markers of bone metabolism, can be used to distinguish bone development in children with SCD from that of nonaffected controls.
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PMID:Assessment of the bone status of Nigerian children and adolescents with sickle cell disease using calcaneal ultrasound and serum markers of bone metabolism. 1220 Jun 47

All 302 children treated at the rheumatology clinic of a children's hospital in Santo Domingo between September 1985 and September 1986 were included in a prospective study of the causes of joint pain in children. The 137 girls and 165 boys were grouped in five categories according to the underlying condition. The largest group, reactive arthritic conditions, affected 78 patients (25.9%). 72 of the 78 had rheumatic fever. The second largest category, hematological processes, affected 75 patients (22.6%); 40 of the 75 patients had sickle cell disease, 25 had hemophilia or other conditions, and 8 had neoplasias. 63 patients (20.8%) had infectious processes, including 33 with septic arthritis, 17 with abscesses and cellulitis, 7 with arthritis and osteomyelitis, and 6 with osteomyelitis. Prostration and pain on movement were more pronounced in patients with septic arthritis. 42 children (12.6%) had collagen vascular disease. 32 had juvenile rheumatoid arthritis, 4 had lupus, 3 vasculitis, 2 dermatomyositis, and 1 each had scleroderma and erythum nodosum. 25 patients (8.2%) had a miscellaneous array of other conditions. Sickle cell disease or neoplasia were most likely when anemia was also present. Extreme prostration and signs of inflammation suggested infectious processes. The small joints were primarily affected in juvenile rheumatoid arthritis and sickle cell disease.
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PMID:[Causes of joint pain in children]. 1229 May 50

Decreased visual acuity and loss of visual ability are devastating anesthetic and surgical complications. The incidence is greater in patients with preexisting hypertension, diabetes, sickle cell anemia, renal failure, gastrointestinal ulcer, narrow-angle glaucoma, vascular occlusive disease, cardiac disease, arteriosclerosis, polycythemia vera, and collagen vascular disorders. Precipitating factors for ischemic optic neuropathy include prolonged hypotension, anemia, surgery, trauma, gastrointestinal bleeding, hemorrhage, shock, prone position, direct pressure on the globe, and long operative times. Prone and Trendelenburg positions can lead to visual loss related to decreased venous return from the head. Visual impairment may result from increased intracranial pressure, which contributes to undue pressure on the optic nerve. The prone position increases the risk of direct compression injury to the orbit and corneal abrasion. Astute attention to positioning is imperative, especially with the prone position. At-risk patients should receive transfusion once the calculated allowable blood loss has been surpassed. Unacceptable hemoglobin and hematocrit values should be corrected preoperatively and levels monitored during the case to avoid intraoperative anemia in at-risk patients. The blood pressure of patients with predisposing diseases should be kept within normal limits. To avoid this devastating complication, it is imperative that anesthesia providers understand contributing factors and prevention strategies.
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PMID:Visual loss as a complication of nonophthalmologic surgery: a review of the literature. 1563 61

Halothane as a cause of hepatitis is rare and may be overlooked when evaluating a patient with sudden onset jaundice. A 34-year-old lady, a nurse, presented to the liver clinic with sudden onset non-pruritic jaundice. Viral and collagen serological tests were all normal, malaria and sickling tests were negative, but transaminases were elevated. She reported inadvertent exposure to halothane in surgical theatre where she works. She improved on conservative management, then had a re-exposure to halothane after three weeks and developed a similar clinical picture, which improved on conservative management. In an area endemic of malaria, hepatitis and haemolysing conditions like sickle cell anaemia, the diagnosis of halothane hepatitis requires high index of suspicion. The mechanism of halothane-induced hepatic damage in this patient is very likely idiosyncratic. This is because of the modest dose at first exposure and more severe clinical picture at re-exposure.
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PMID:Halothane induced hepatitis: case report. 1571 33

Decreased visual acuity and loss of visual ability are devastating anesthetic and surgical complications. The incidence is greater in patients with preexisting hypertension, diabetes, sickle cell anemia, renal failure, gastrointestinal ulcer, narrow-angle glaucoma, vascular occlusive disease, cardiac disease, arteriosclerosis, polycythemia vera, and collagen vascular disorders. Precipitating factors for ischemic optic neuropathy include prolonged hypotension, anemia, surgery trauma, gastrointestinal bleeding, hemorrhage, shock, prone position, direct pressure on the globe, and long operative times. Prone and Trendelenburg positions can lead to visual loss related to decreased venous return from the head. Visual impairment may result from increased intracranial pressure, which contributes to undue pressure on the optic nerve. The prone position increases the risk of direct compression injury to the orbit and corneal abrasion. Astute attention to positioning is imperative, especially with the prone position. At-risk patients should receive transfusion once the calculated allowable blood loss has been surpassed Unacceptable hemoglobin and hematocrit values should be corrected preoperatively and levels monitored during the case to avoid intraoperative anemia in at-risk patients. The blood pressure of patients with predisposing diseases should be kept within normal limits. To avoid this devastating complication, it is imperative that anesthesia providers understand contributing factors and prevention strategies.
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PMID:Visual loss as a complication of non-ophthalmic surgery: a review of the literature. 1594 13

Previously we showed L-4F, a novel apolipoprotein A-I (apoA-I) mimetic, improved vasodilation in 2 dissimilar models of vascular disease: hypercholesterolemic LDL receptor-null (Ldlr(-/-)) mice and transgenic sickle cell disease mice. Here we determine the mechanisms by which D-4F improves vasodilation and arterial wall thickness in hypercholesterolemic Ldlr(-/-) mice and Ldlr(-/-)/apoA-I null (apoA-I(-/-)), double-knockout mice. Ldlr(-/-) and Ldlr(-/-)/apoA-I(-/-) mice were fed Western diet (WD) with and without D-4F. Oral D-4F restored endothelium- and endothelial NO synthase (eNOS)-dependent vasodilation in direct relationship to duration of treatments and reduced wall thickness in as little as 2 weeks in vessels with preexisting disease in Ldlr(-/-) mice. D-4F had no effect on total or HDL cholesterol concentrations but reduced proinflammatory HDL levels. D-4F had no effect on plasma myeloperoxidase concentrations but reduced myeloperoxidase association with apoA-I as well as 3-nitrotyrosine in apoA-I. D-4F increased endothelium- and eNOS-dependent vasodilation in Ldlr(-/-)/apoA-I(-/-) mice but did not reduce wall thickness as it had in Ldlr(-/-) mice. Vascular endothelial cells were treated with 22(R)-hydroxycholesterol with and without L-4F. 22(R)-Hydroxycholesterol decreased NO (*NO) and increased superoxide anion (O2*-) production and increased ATP-binding cassette transporter-1 and collagen expression. L-4F restored *NO and O2*- balance, had little effect on ATP-binding cassette transporter-1 expression, but reduced collagen expression. These data demonstrate that although D-4F restores vascular endothelial cell and eNOS function to increase vasodilation, HDL containing apoA-I, or at least some critical concentration of the antiatherogenic lipoprotein, is required for D-4F to decrease vessel wall thickness.
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PMID:Effects of D-4F on vasodilation and vessel wall thickness in hypercholesterolemic LDL receptor-null and LDL receptor/apolipoprotein A-I double-knockout mice on Western diet. 1630 51

Bone disease with osteoporosis and osteomalacia are common in sickle cell disease (SCD). Some patients have vitamin D deficiency and low bone mineral density (BMD). The role of vitamin D and calcium supplementation to restore bone health in SCD has not been well studied. In 14 adults with SCD, we measured 25(OH)D (25-hydroxyvitamin D) and BMD at the femoral neck, lumbar spine, and distal third of the ulna plus radius, along with markers of bone resorption (CTx; C-terminal component of pro-collagen type I) and bone formation (osteocalcin) before and after 12 months of vitamin D(2) and calcium carbonate treatment. Pretreatment, all patients were vitamin D deficient with a mean 25(OH)D level of 11.6 [corrected] +/- 4 [corrected] ng/ml, had low BMD at the lumbar spine (L-spine), 0.87 +/- 0.11 g/cm(2) (mean Z-score of -2.6 3 +/- 0.71 SD and T score of -2.31 +/- 0.75 SD), femoral neck, 0.8 +/- 0.18 g/cm(2) (mean Z-score -1.36 +/- 0.84, T-score -1.14 +/- 0.75), and the distal radius and ulna, 0.6 +/- 0.17 g/cm(2) (mean Z-score -1.18 +/- 0.79, T-score -1.01 +/- 0.74) and had elevated CTx (0.87 +/- 0.5 ng/ml) and osteocalcin levels (12.3 +/- 3.7 ng/mul). After treatment, all patients corrected their 25(OH)D level (34.6 [corrected] +/- 11 [corrected] ng/ml) (P < 0.001) with a 3.6% +/- 3.9% increase in BMD at the L-spine (P = 0.009), 4.6% +/- 8.5% increase at the femoral neck (P = 0.05) and 6.5% +/- 12.6% increase at the distal radius plus ulna (P = 0.09). CTx, osteocalcin, and PTH(i) levels were unchanged. Treatment of adult SCD with vitamin D and calcium can restore 25(OH)D levels to normal and improve BMD, but, markers of bone resorption remained unchanged. Screening for vitamin D deficiency and BMD in SCD patients seems warranted.
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PMID:Sickle cell bone disease: response to vitamin D and calcium. 1792 48

Examples of single gene disorders have been described for all major subtypes of ischaemic stroke: accelerated atherosclerosis and subsequent thrombo-embolism (e.g. homocysteinuria), weakening of connective tissue resulting in arterial dissections (e.g. Ehler-Danlos type IV), disorders of cerebral small vessels (e.g. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and the collagen COL4A1 mutation), disorders increasing the thrombogenic potential of the heart through affecting the myocardium or the heart valves or through disturbance of the heart rhythm (e.g. hypertrophic cardiomyopathy), mitochondrial cytopathies increasing cerebral tissue susceptibility to insults (e.g. mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes), and finally disorders of coagulation that can either directly cause stroke or act synergistically with the aforementioned abnormalities (e.g. sickle cell disease). Most of these disorders are rare but they are important to consider particularly in young patients with stroke, those with a family history or those who have other characteristics of a particular syndrome.
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PMID:Genetics of ischaemic stroke; single gene disorders. 1870 33

Phosphatidylserine (PS)-dependent erythrocyte adhesion to endothelium and subendothelial matrix components is mediated in part via thrombospondin (TSP). Although TSP exhibits multiple cell-binding domains, the PS-binding site on TSP is unknown. Because a cell-binding domain for anionic heparin is located at the amino-terminus, we hypothesized that PS-positive red blood cells (PS(+ve)-RBCs) bind to this domain. We demonstrate that both heparin and its low-molecular-weight derivative enoxaparin (0.5-50 u/mL) inhibited PS(+ve)-RBC adhesion to immobilized TSP in a concentration-dependent manner (21% to 77% inhibition, P < 0.05). Preincubation of immobilized TSP with an antibody against the heparin-binding domain blocked PS(+ve)-RBC adhesion to TSP. Antibodies that recognize the collagen- and the carboxy-terminal CD47-binding domain on TSP had no effect on this process. Although preincubation of PS(+ve)-RBCs with TSP peptides from the heparin-binding domain that contained the specific heparin-binding motif KKTRG inhibited PS(+ve)-erythrocyte adhesion to matrix TSP (P < 0.001), these peptides in the immobilized form supported PS-mediated erythrocyte adhesion. A TSP-peptide that lacks the binding motif neither inhibited nor supported PS(+ve)-RBC adhesion. Additional experiments show that soluble TSP also interacted with PS(+ve)-RBCs via its heparin-binding domain. Our results demonstrate that PS-positive erythrocytes bind to both immobilized and soluble TSP via its heparin-binding domain and that both heparin and enoxaparin, at clinically relevant concentrations, block this interaction. Other studies have shown that heparin inhibited P-selectin- and soluble-TSP-mediated sickle erythrocyte adhesion to endothelial cells. Our results, taken together with the previously documented findings, provide a rational basis for clinical use of heparin or its low-molecular-weight derivatives as therapeutic agents in treating vaso-occlusive pain in patients with sickle cell disease.
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PMID:Phosphatidylserine-positive erythrocytes bind to immobilized and soluble thrombospondin-1 via its heparin-binding domain. 1894 Jul 19


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