scholarly journals A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease

Nitric Oxide ◽  
2018 ◽  
Vol 74 ◽  
pp. 19-22 ◽  
Author(s):  
Alphonce I. Marealle ◽  
Mario Siervo ◽  
Sara Wassel ◽  
Les Bluck ◽  
Andrew M. Prentice ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Whole Body ◽  
No Production ◽  
Cell Disease ◽  
Non Invasive ◽  
Isotopic Method ◽  
Stable Isotopic

scholarly journals Non-Invasive Characterization of Oxygen Transport in Sickle Cell Disease: A Pilot Study

2015 ◽  
Vol 1 (3) ◽  
pp. 89-95
Author(s):  
Imoigele P. Aisiku ◽  
◽  
Osama R. Kandalaft ◽  
Wally R. Smith ◽  
Lynne T. Penberthy ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Oxygen Transport ◽  
Cell Disease ◽  
Non Invasive

Computerized cognitive training in pediatric sickle cell disease: A randomized controlled pilot study.

2020 ◽  
Vol 8 (4) ◽  
pp. 390-401 ◽  
Author(s):  
Taryn M. Allen ◽  
Lindsay M. Anderson ◽  
Samuel M. Brotkin ◽  
Jennifer A. Rothman ◽  
Melanie J. Bonner
Keyword(s):  
Pilot Study ◽  
Sickle Cell Disease ◽  
Cognitive Training ◽  
Sickle Cell ◽  
Cell Disease ◽  
Computerized Cognitive Training ◽  
Randomized Controlled ◽  
Pediatric Sickle Cell Disease

scholarly journals VEGF Promoter Region 18-bp Insertion-Deletion Polymorphism in Sickle Cell Disease Patients with Microalbuminuria: A Pilot Study

2018 ◽  
Vol 35 (2) ◽  
pp. 278-283
Author(s):  
Dnyanesh B. Amle ◽  
Rachana L. Patnayak ◽  
Varsha Verma ◽  
Gajendra Kumar Singh ◽  
Vijaylakshmi Jain ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Promoter Region ◽  
Cell Disease ◽  
Deletion Polymorphism

scholarly journals A pilot study of the effect of atorvastatin on endothelial function and albuminuria in sickle cell disease

2019 ◽  
Vol 94 (11) ◽  
Author(s):  
Kenneth I. Ataga ◽  
David Wichlan ◽  
Laila Elsherif ◽  
Vimal K. Derebail ◽  
Adane F. Wogu ◽  
...  
Keyword(s):  
Pilot Study ◽  
Sickle Cell Disease ◽  
Endothelial Function ◽  
Sickle Cell ◽  
Cell Disease

scholarly journals Non-Invasive Prenatal Diagnosis (NIPD) of Sickle-Cell Disease By Massively Parallel Sequencing of Cell-Free Fetal DNA in Maternal Serum

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2085-2085
Author(s):  
Yvonne Daniel ◽  
Julia Van Campen ◽  
Lee Silcock ◽  
Michael Yau ◽  
Joo Wook Ahn ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Massively Parallel Sequencing ◽  
Plasma Samples ◽  
Cell Disease ◽  
Cell Free Dna ◽  
Non Invasive ◽  
Free Dna ◽  
Cell Free Fetal Dna

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide. Around 300.000 affected infants are born every year, including at least 1000 in the United States. Prenatal diagnosis is currently carried out using amniotic fluid or chorionic villus sampling. These invasive procedures are perceived to have a small risk of miscarriage. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived miscarriage risk. NIPD may also be more readily implemented than invasive prenatal diagnosis in the low-resource countries in which SCD is the most prevalent. However, accurate NIPD of autosomal recessive disorders such as sickle cell disease has proven challenging as this requires detection of fetal inheritance of a maternal allele from a mixed maternal-fetal pool of cell-free DNA. We report the development of a targeted massively parallel sequencing assay for the NIPD of fetal SCD using cell-free fetal DNA from maternal plasma. No paternal or previous offspring samples were required. 44 clinical samples were analysed, including 37 plasma samples from pregnant SCD carriers and 7 plasma samples from women with SCD due to Hb SC. We used a relative mutation dosage based approach for the 37 samples from maternal SCD carriers (Hb AS or Hb AC), integrating Unique Molecular Identifiers (UMIs) into the analysis to improve the accuracy of wildtype and mutant allele counts. We used a separate wildtype allele detection approach for the 7 samples from women with compound heterozygous SCD, in whom the detection of wildtype cell-free DNA indicates the presence of a carrier fetus. The success of the assay was evaluated by comparing results with the established fetal sickle status as determined through either invasive prenatal diagnosis or newborn screening. During development, two key factors improved the accuracy of the results: i) Selective analysis of only smaller cell-free DNA fragments enhanced the fetal fraction for all samples, with greater effects observed in samples from earlier gestations. This approach improved diagnostic accuracy: for 3 out of 44 samples, the genotype was inconclusive or incorrect before size selection, but correct after size selection. ii) Modifications to DNA fragment hybridisation capture optimised the diversity of Unique Molecular Identifier-tagged molecules analysed. This led to improvements in the results obtained for 5 samples, with 3 previously inconclusive samples correctly called and 2 previously discrepant results moved into the inconclusive range. In total, 37 results were concordant with the established fetal sickle status; this included 30/37 samples from carrier women and 7/7 samples from women with sickle cell disease due to Hb SC. The remaining 7 carrier samples gave an inconclusive result, which for 3 samples was attributed to a low fetal fraction. Samples from as early as 8 weeks gestation were successfully genotyped. There were no false positive or false negative results. This study is the largest to use NGS-based NIPD on clinical plasma samples from pregnancies at risk of SCD. Efforts to validate the assay on a larger sample cohort and to reduce the inconclusive rate are warranted. This study shows that NIPD for SCD is approaching clinical utility and has the potential to provide increased choice to women with pregnancies at risk of sickle cell disease. Disclosures Silcock: Nonacus Ltd.: Employment.

Screening for Obstructive Sleep Apnea in Children With Sickle Cell Disease: A Pilot Study

2020 ◽  
Author(s):  
Andrew J. Maroda ◽  
Matthew N. Spence ◽  
Stephen R. Larson ◽  
Jeremie H. Estepp ◽  
M. Boyd Gillespie ◽  
...  
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Pilot Study ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Obstructive Sleep

Non-invasive urinary biomarkers of renal function in sickle cell disease: an overview

2019 ◽  
Vol 98 (12) ◽  
pp. 2653-2660
Author(s):  
Marília Rocha Laurentino ◽  
Sérgio Luiz Arruda Parente Filho ◽  
Lívia Leal Chagas Parente ◽  
Geraldo Bezerra da Silva Júnior ◽  
Elizabeth De Francesco Daher ◽  
...  
Keyword(s):  
Renal Function ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Urinary Biomarkers ◽  
Cell Disease ◽  
Non Invasive

Cerebral Oxygen Saturation in Sickle Cell Patients Treated with Hydroxyurea:.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1677-1677
Author(s):  
Masoud Nahavandi ◽  
Fatemeh Tavakkoli ◽  
Melville Q. Wyche ◽  
Syed P. Hasan ◽  
Oswaldo Castro
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Sickle Cell ◽  
Cerebral Oxygenation ◽  
Cerebral Oximetry ◽  
Cerebral Oxygen Saturation ◽  
Cerebral Oxygen ◽  
Cell Disease ◽  
Non Invasive

Abstract Recently we reported the use of a non-invasive near-infrared optical spectroscopy technique to measure cerebral oxygenation (cerebral oximetry, rSO2%) in agroup of 27 adult patients with sickle cell disease (Eur J Clin Invest, 34:143,2004). The sickle cell patients’ rSO2 values were significantly lower (mean 47.7%) than those in normal subjects (mean 61.3%) even though none of the patients had clinical evidence of stroke or cerebral ischemia. We included patients with all Hb phenotypes, and regardless of hydroxyurea (HU) treatment. Transfusions improved cerebral oxygen saturation but the post-transfusion values still did not reach normal levels. Our findings were corroborated independently by Raj et al. who studied 25 children with sickle cell disease (J Pediat Hematol Oncol 26:279,2004). In order to determine if long-term HU treatment affects rSO2, we analyzed cerebral oximetry results in a subset of 31 patients with sickle cell anemia (Hb SS). Eleven of them were on long-term (more than 6 months) HU treatment at stable doses (1000–1500 mg/day). The table shows that the mean rSO2, Hb, Hct, and MCV in HU-treated patients were significantly higher than those in sickle cell anemia (SCA) patients not on HU. The rSO2 in HU-treated patients was 12.5% higher than in SS patients not on this drug. By comparison, we previously reported a 24% increment in rSO2 following transfusions. A group of 8 patients who were on long-term HU treatment were given also single 1000 mg oral doses of HU and their rSO2 was measured for 12 hours without noticeable change in cerebral oxygenation. Nor did rSO2 change after oxygen inhalation (3L/min). The cause of the low rSO2 in sickle cell patients is unknown and still under investigation. It is probably not related exclusively to the anemia, since, as previously reported, anemic subjects without sickle cell disease appear to have normal rSO2. These preliminary results indicate that chronic HU treatment is associated with higher rSO2 values in SCA. If validated in a larger number of patients, our findings suggest that cerebral oximetry could be a useful, non-invasive method for assessing a new in vivo effect of HU and red cell transfusion in sickle cell disease: increased blood oxygen saturation in the cerebral vasculature. HYDROXYUREA AND CEREBRAL OXYGEN SATURATION IN PATIENTS WITH SICKLE CELL DISEASE NO HYDROXYUREA (N=20) HYDROXYUREA (N=11) P value* rSO2 = cerebral oxygen saturation. *= t-test. Plus/minus figures represent SD Mean rSO2 (%) 41 ± 6.6 46 ± 7.6 0.025 Mean Hb (g/dl) 8.4 ± 1.4 9.68 ± 1.2 0.029 Mean Hct (%) 24± 3.4 28± 4.4 0.027 Mean MCV (fl) 89± 8 102± 7 0.028

Tetrahydrobiopterin (6R-BH4): Novel Therapy for Endothelial Dysfunction in Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. lba-5-lba-5 ◽  
Author(s):  
Lewis Hsu ◽  
Kenneth I Ataga ◽  
Victor R. Gordeuk ◽  
Paul S. Swerdlow ◽  
Abdullah Kutlar ◽  
...  
Keyword(s):  
Folic Acid ◽  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Endothelial Function ◽  
Sickle Cell ◽  
No Production ◽  
Central Feature ◽  
Cell Transplant ◽  
Cell Disease ◽  
Dose Dependent

Abstract Dysregulated nitric oxide (NO) homeostasis, a consequence of hemolysis, is a central feature of endothelial dysfunction (ED) in Sickle Cell disease (SCD). In addition to ED, scavenging of NO by free heme leads to increased cell adhesion and inflammation. Vascular inflammation and the production of superoxide may decrease BH4, an essential cofactor for NO production, thus creating an acquired BH4 deficiency. Restoring BH4 levels could potentially improve ED thereby favorably impacting complications of SCD. We assessed the safety and efficacy of 6R-BH4 on endothelial function in a Phase 2a, open-label, dose escalation study in SCD subjects using a non-invasive, operatorindependent technique of peripheral arterial tonometry (Endo-PAT; Itamar, Israel). Endo-PAT (PAT) scores were quantitatively determined as the ratio between the arterial pulse wave amplitude following a 5 min arterial occlusion in the forearm to the pre-occlusion value. A value of ≤1.67 represents an impaired response or endothelial dysfunction. Only patients with HbSS and HbSC disease and at least 15 years of age were enrolled. Patients were excluded if they: were on chronic hypertransfusion; had sickle cell crisis within 30 days of screening; had a history of bone marrow or stem cell transplant or were on hydroxyurea (HU) therapy during the 3 months prior to screening. Thirty-two African-American subjects, mean age 29 years (41% male) were sequentially treated for 4 weeks each with 6R-BH4 at 2.5, 5, 10, and 20 mg/kg/day at 12 US sites. Nine subjects discontinued therapy for various reasons including loss of follow up and pregnancy. Twenty-seven subjects had baseline PAT scores and the number of subjects with PAT scores varied at each treatment dose. There were no deaths and only one subject had a drug related adverse effect resulting in discontinuation. Overall, 6R-BH4 is safe and well-tolerated in subjects with SCD. The mean PAT scores for all participants at baseline was 1.58 ± 0.43 (mean ± SD). Mean PAT scores at baseline were 1.33 ± 0.17 in 18 patients with abnormal PAT scores and 2.09 ± 0.31 (p=<0.001) in 9 patients with normal PAT scores. Mean PAT score for all subjects demonstrated significant improvement at 5mg/kg/day and 10mg/kg/day (dose, N, mean change +/− SD, mean % change and p value) (5 mg/kg/day, N=24, 1.79 ± 0.64, 22.4%, p= 0.042; 10 mg/kg/day, N=24, 1.95 ± 0.46, 28.2%, p=0.003). Eighteen of the 27 (67%) subjects who had abnormal PAT scores at baseline had statistically significant dose-dependent improvements over the 16 weeks of therapy with 6R-BH4 (2.5 mg/kg, N=15, 1.63 ± 0.37, 24.7%, p=0.012; 5mg/kg, N=14, 1.69 ± 0.56, 31.2%, p=0.025; 10mg/kg, N=15, 1.84 ± 0.47, 39.9%, p<0.001; 20mg/kg, N=15, 2.01 ± 0.76, 56.6%, p=0.005). Consistent with the mechanism of action of 6R-BH4 subjects with normal Endo-PAT scores at baseline demonstrated no improvement with therapy. HbSS subjects appear to have more ED based on PAT scores compared with HbSC subjects, although the difference was not statistically significant 1.52 ± 0.45 vs 1.67 ± 0.39. More importantly, both HbSS and HbSC subjects demonstrated an improvement in mean change in endothelial function with increasing doses of 6R-BH4 with corresponding % mean changes from baseline being 48.8% and 15.5% respectively following 16 weeks of treatment. The majority of subjects in the study (17/27; 63%) were prescribed folic acid supplement by their physicians at baseline and throughout the study. Post hoc analysis demonstrated no difference in baseline PAT scores between subjects on folic acid supplementation and those not on it (1.60 ± 0.47 vs 1.55 ± 0.37). However, patients on folic acid demonstrated a better dose response to treatment with 6R-BH4 compared to patients not receiving folic acid (2.5 mg/kg: 1.72 ± 0.38 vs 1.69 ± 0.41; 5mg/kg: 1.93 ± 0.74 vs 1.56 ± 0.38; 10mg/kg: 1.89 ± 0.51 vs 2.06 ± 0.34; 20 mg/kg: 2.09 ± 0.73 vs 1.62 ± 0.34) In summary, 6R-BH4 is safe, well-tolerated and demonstrates a dose-dependent improvement in endothelial function in subjects with SCD. Best results were achieved in those with baseline endothelial dysfunction. Improvement in ED occurs regardless of genotype. Finally, patients receiving folic acid showed a better response to 6R-BH4 than those not receiving this supplement. These data provide further support for the development of 6R-BH4 as a treatment for sickle cell disease. 6R-BH4 is a potentially new effective modulator of NO for SCD patients who have ED.

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