Glomerular function in sickle cell disease patients during crisis.

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Aderibigbe, A; Arije, A; Akinkugbe, O O

1994-06-01

An 8 month prospective study was carried out in 20 adult sickle cell disease (SCD) patients 16 sickle cell anaemia (Hbss) and 4 sickle cell Hbc disease (Hbsc); who had vaso-occlusive crises within the study period to determine the extent of the effect of sickle cell crisis on glomerular function in SCD patients during crisis. The male: female ratio was 1:57 and their mean age was 21.1 +/- 7.9 years. Creatinine clearance (CCr), as an index of glomerular function, was determined at the pre-crisis, crisis, 2 and 4 weeks post-crisis and at the end of the study period. The mean values of their CCr dropped from 113.37 +/- 33.80mls/min at pre-crisis stage to 96.39 +/- 30.13mls/min during crisis (p pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

IMPACT OF MANNOSE-BINDING PROTEIN GENE POLYMORPHISMS IN OMANI SICKLE CELL DISEASE PATIENTS

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Mathew Zachariah

2016-02-01

Full Text Available Objectives: Our objective was to study mannose binding protein (MBP polymorphisms in exonic and promoter region and correlate associated infections and vasoocculsive (VOC episodes, since MBP plays an important role in innate immunity by activating the complement system. Methods: We studied the genetic polymorphisms in the Exon 1 (alleles A/O and promoter region (alleles Y/X; H/L, P/Q of the MBL2 gene, in sickle cell disease (SCD patients as increased incidence of infections is seen in these patients. A PCR-based, targeted genomic DNA sequencing of MBL2 was used to study 68 SCD Omani patients and 44 controls (voluntary blood donors. Results: The observed frequencies of MBL2 promoter polymorphism (-221, Y/X were 44.4% and 20.5% for the heterozygous genotype Y/X and 3.2% and 2.2% for the homozygous (X/X respectively between SCD patients and controls. MBL2 Exon1 gene mutations were 29.4% and 50% for the heterozygous genotype A/O and 5.9% and 6.8% respectively for the homozygous (O/O genotype between SCD patients and controls. The distribution of variant MBL2 polymorphisms did not show any correlation in SCD patients with or without vasoocculsive crisis (VOC attacks (p=0.162; OR-0.486; CI=0.177 -1.33, however, it was correlated with infections (p=0.0162; OR-3.55; CI 1.25-10.04. Conclusions: Although the frequency of the genotypes and haplotypes of MBL2 in SCD patients did not differ from controls, overall in the SCD patient cohort the increased representation of variant alleles was significantly correlated with infections (p<0.05. However, these variant MBL2 polymorphisms did not seem to play a significant role in the VOC episodes in this SCD cohort. Keywords: Mannose-binding lectin, polymorphism, promoter, Sickle cell disease, MBL2, MBP

Serum sCD30 in monitoring of alloresponse in well HLA-matched cadaveric kidney transplantations.

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Matinlauri, Irma H; Kyllönen, Lauri E J; Salmela, Kaija T; Helin, Heikki; Pelzl, Steffen; Süsal, Caner

2005-12-27

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (PsCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

Patent Foramen Ovale in Patients with Sickle Cell Disease and Stroke: Case Presentations and Review of the Literature

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Sheila Razdan

2013-01-01

Full Text Available Although individuals with sickle cell disease (SCD are at increased risk for stroke, the underlying pathophysiology is incompletely understood. Intracardiac shunting via a patent foramen ovale (PFO is associated with cryptogenic stroke in individuals without SCD. Recent evidence suggests that PFOs are associated with stroke in children with SCD, although the role of PFOs in adults with stroke and SCD is unknown. Here, we report 2 young adults with SCD, stroke, and PFOs. The first patient had hemoglobin SC and presented with a transient ischemic attack and a subsequent ischemic stroke. There was no evidence of cerebral vascular disease on imaging studies and the PFO was closed. The second patient had hemoglobin SS and two acute ischemic strokes. She had cerebral vascular disease with moyamoya in addition to a peripheral deep venous thrombosis (DVT. Chronic transfusion therapy was recommended, and the DVT was managed with warfarin. The PFO was not closed, and the patients' neurologic symptoms were stabilized. We review the literature on PFOs and stroke in SCD. Our cases and the literature review illustrate the dire need for further research to evaluate PFO as a potential risk factor for stroke in adults with SCD.

Posttransplant sCD30 as a predictor of kidney graft outcome.

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Süsal, Caner; Döhler, Bernd; Sadeghi, Mahmoud; Salmela, Kaija T; Weimer, Rolf; Zeier, Martin; Opelz, Gerhard

2011-06-27

Reliable markers for assessing the biological effect of immunosuppressive drugs and identification of transplant recipients at risk of developing rejection are not available. In a prospective multicenter study, we investigated whether posttransplant measurement of the T-cell activation marker soluble CD30 (sCD30) can be used for estimating the risk of graft loss in kidney transplant recipients. Pre- and posttransplant sera of 2322 adult deceased-donor kidney recipients were tested for serum sCD30 content using a commercial enzyme-linked immunosorbent assay. sCD30 decreased posttransplant and reached a nadir on day 30. Patients with a high sCD30 of more than or equal to 40 U/mL on day 30 showed a subsequent graft survival rate after 3 years of 78.3±4.1%, significantly lower than the 90.3±1.0% rate in recipients with a low sCD30 on day 30 of less than 40 U/mL (log-rank PsCD30 levels, patients with high sCD30 on posttransplant day 30 demonstrated significantly lower 3-year graft survival irrespective of the pretransplant level. Our data suggest that posttransplant measurement of sCD30 on day 30 is a predictor of subsequent graft loss in kidney transplant recipients and that sCD30 may potentially serve as an indicator for adjustment of immunosuppressive medication.

Increased theta band EEG power in sickle cell disease patients

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Case M

2017-12-01

Full Text Available Michelle Case,1 Sina Shirinpour,1 Huishi Zhang,1 Yvonne H Datta,2 Stephen C Nelson,3 Karim T Sadak,4 Kalpna Gupta,2 Bin He1,5 1Department of Biomedical Engineering, 2Department of Medicine, University of Minnesota, 3Pediatric Hematology-Oncology, Children’s Hospitals and Clinics of Minnesota, 4Pediatric Hematology-Oncology, University of Minnesota Masonic Children’s Hospital, 5Institute for Engineering in Medicine, University of Minnesota, Minneapolis, MN, USA Objective: Pain is a major issue in the care of patients with sickle cell disease (SCD. The mechanisms behind pain and the best way to treat it are not well understood. We studied how electroencephalography (EEG is altered in SCD patients. Methods: We recruited 20 SCD patients and compared their resting state EEG to that of 14 healthy controls. EEG power was found across frequency bands using Welch’s method. Electrophysiological source imaging was assessed for each frequency band using the eLORETA algorithm. Results: SCD patients had increased theta power and decreased beta2 power compared to controls. Source localization revealed that areas of greater theta band activity were in areas related to pain processing. Imaging parameters were significantly correlated to emergency department visits, which indicate disease severity and chronic pain intensity. Conclusion: The present results support the pain mechanism referred to as thalamocortical dysrhythmia. This mechanism causes increased theta power in patients. Significance: Our findings show that EEG can be used to quantitatively evaluate differences between controls and SCD patients. Our results show the potential of EEG to differentiate between different levels of pain in an unbiased setting, where specific frequency bands could be used as biomarkers for chronic pain. Keywords: sickle cell disease, electroencephalography, chronic pain, electrophysiological source imaging, thalamocortical dysrhythmia

Acute Chest Syndrome in Sickle Cell Disease Patients Post Caesarean Delivery

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YM Zhang

2016-02-01

Full Text Available Sickle cell disease (SCD is the most common inherited disease worldwide and is associated with anaemia and intermittent painful crisis. Pregnant women who are affected are known to have increased maternal and fetal mortality and morbidity. Acute chest syndrome (ACS is an uncommon but serious complication in pregnant women with SCD that can lead to death. We present two cases of patients with SCD, both of whom had severe ACS within 24 hours post Caesarean section. By accurate diagnosis and appropriate management by a multidisciplinary team, both mothers and fetuses had excellent outcomes. It is suggested that prompt recognition of ACS in a pregnant woman with SCD and collaborative medical and obstetric management are essential to optimize maternal and fetal outcomes.

High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

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Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

2007-10-01

Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values 30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

Multicenter COMPACT study of COMplications in patients with sickle cell disease and utilization of iron chelation therapy.

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Jordan, Lanetta; Adams-Graves, Patricia; Kanter-Washko, Julie; Oneal, Patricia A; Sasane, Medha; Vekeman, Francis; Bieri, Christine; Magestro, Matthew; Marcellari, Andrea; Duh, Mei Sheng

2015-03-01

Over the past few decades, lifespans of sickle cell disease (SCD) patients have increased; hence, they encounter multiple complications. Early detection, appropriate comprehensive care, and treatment may prevent or delay onset of complications. We collected longitudinal data on sickle cell disease (SCD) complication rates and associated resource utilization relative to blood transfusion patterns and iron chelation therapy (ICT) use in patients aged ≥16 years to address a gap in the literature. Medical records of 254 SCD patients ≥16 years were retrospectively reviewed at three US tertiary care centers. We classified patients into cohorts based on cumulative units of blood transfused and ICT history: ICT (Cohort 1 [C1]), ≥15 units, no ICT (Cohort 2 [C2]), and ≥15 units with ICT (Cohort 3 [C3]). We report SCD complication rates per patient per year; cohort comparisons use rate ratios (RRs). Cohorts had 69 (C1), 91 (C2), and 94 (C3) patients. Pain led to most hospitalizations (76%) and emergency department (ED) (82%) visits. Among transfused patients (C2+C3), those receiving ICT were less likely to experience SCD complications than those who did not (RR [95% CI] C2 vs. C3: 1.33 [1.25-1.42]). Similar trends (RR [95% CI]) were observed in ED visits and hospitalizations associated with SCD complications (C2 vs. C3, ED: 1.94 [1.70-2.21]; hospitalizations: 1.61 [1.45-1.78]), but not in outpatient visits. Although the most commonly reported SCD complication among all patients was pain, patients who received ICT were less likely to experience pain and other complications than those who did not. These results highlight the need for increased patient and provider education on the importance of comprehensive disease management.

Tract specific analysis in patients with sickle cell disease

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Chai, Yaqiong; Coloigner, Julie; Qu, Xiaoping; Choi, Soyoung; Bush, Adam; Borzage, Matt; Vu, Chau; Lepore, Natasha; Wood, John

2015-12-01

Sickle cell disease (SCD) is a hereditary blood disorder in which the oxygen-carrying hemoglobin molecule in red blood cells is abnormal. It affects numerous people in the world and leads to a shorter life span, pain, anemia, serious infections and neurocognitive decline. Tract-Specific Analysis (TSA) is a statistical method to evaluate white matter alterations due to neurocognitive diseases, using diffusion tensor magnetic resonance images. Here, for the first time, TSA is used to compare 11 major brain white matter (WM) tracts between SCD patients and age-matched healthy subjects. Alterations are found in the corpus callosum (CC), the cortico-spinal tract (CST), inferior fronto-occipital fasciculus (IFO), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and uncinated fasciculus (UNC). Based on previous studies on the neurocognitive functions of these tracts, the significant areas found in this paper might be related to several cognitive impairments and depression, both of which are observed in SCD patients.

Hydroxyurea in Pediatric Patients With Sickle Cell Disease: What Nurses Need to Know.

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Rees, Allison L

2016-09-01

Sickle cell disease (SCD) is an inherited disorder in which sickled red blood cells occlude the small vessels of the body, reducing oxygen delivery to tissues and ultimately negatively affecting many of the body's major organs. Hydroxyurea has proven beneficial in the treatment of SCD and prevention of disease-related complications. The 2014 guidelines put forth by the National Heart, Lung, and Blood Institute recommend hydroxyurea treatment in infants 9 months and older, children, and adolescents with SCD-SS or SCD-Sβ(0) thalassemia regardless of clinical severity. This is a change from the 2002 guidelines in which hydroxyurea was recommended for adolescents and children with SCD-SS or SCD-Sβ(0) thalassemia with frequent episodes of pain, a history of acute chest syndrome, severe and symptomatic anemia or other severe vaso-occlusive events. Nurses play a critical role in working with patients and families to provide education, guidance, and support to improve compliance to mitigate the long-term effects of SCD. © 2015 by Association of Pediatric Hematology/Oncology Nurses.

Implementation of Indigenous Electronic Medical Record System to Facilitate Care of Sickle Cell Disease Patients in Chhattisgarh.

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Choubey, Mona; Mishra, Hrishikesh; Soni, Khushboo; Patra, Pradeep Kumar

2016-02-01

Sickle cell disease (SCD) is prevalent in central India including Chhattisgarh. Screening for SCD is being carried out by Government of Chhattisgarh. Electronic Medical Record (EMR) system was developed and implemented in two phases. Aim was to use informatics techniques and indigenously develop EMR system to improve the care of SCD patients in Chhattisgarh. EMR systems had to be developed to store and manage: i) huge data generated through state wide screening for SCD; ii) clinical data for SCD patients attending the outpatient department (OPD) of institute. 'State Wide Screening Data Interface' (SWSDI) was designed and implemented for storing and managing data generated through screening program. Further, 'Sickle Cell Patients Temporal Data Management System' (SCPTDMS) was developed and implemented for storing, managing and analysing sickle cell disease patients' data at OPD. Both systems were developed using VB.Net and MS SQL Server 2012. Till April 2015, SWSDI has data of 1294558 persons, out of which 121819 and 4087 persons are carriers and patients of sickle cell disease respectively. Similarly till June 2015, SCPTDMS has data of 3760 persons, of which 923 are sickle cell disease patients (SS) and 1355 are sickle cell carriers (AS). Both systems are proving to be useful in efficient storage, management and analysis of data for clinical and research purposes. The systems are an example of beneficial usage of medical informatics solutions for managing large data at community level.

Exploring the link between innate immune activation and thymic function by measuring sCD14 and TRECs in HIV patients living in Belgium.

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Adrien De Voeght

Full Text Available Microbial translocation is now viewed as a central event in the pathogenesis of chronic inflammation during HIV infection. Thymic function failure is another crucial factor involved in HIV disease progression. The goal of this study was to explore the hypothesis of potential links between microbial translocation and thymic function in HIV-1 patients living in Belgium. The extent of microbial translocation was assessed through the measurement of soluble CD14 (sCD14. T-cell receptor excision circles (sjTRECs and dβTRECs were used as a measure of thymic function. Data were collected from 75 HIV-infected patients. Simple and complex linear regressions were done to analyze the link between these two processes. We found a statistically relevant negative correlation between thymopoiesis (sjTREC and sCD14 level (p = 0.004. These results suggest a link between thymic function failure, microbial translocation and innate immune activation.

The macrophage low-grade inflammation marker sCD163 is modulated by exogenous sex steroids

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Thomsen, Henrik Holm; Møller, Holger Jon; Trolle, Christian

2013-01-01

Soluble CD163 (sCD163) is a novel marker linked to states of low grade inflammation such as diabetes, obesity, liver disease and atherosclerosis, all prevalent in subjects with Turner and Klinefelter Syndromes. We aimed to assess the levels of sCD163 and the regulation of sCD163 in regards...

Best practices for transfusion for patients with sickle cell disease

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Ted Wun

2010-01-01

Full Text Available The beta-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research.  A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

Best practices for transfusion for patients with sickle cell disease

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Wun, Ted; Hassell, Kathryn

2010-01-01

The β-globin gene mutation in sickle cell anemia results in anemia and repeated bouts of vascular occlusion. The cumulative effect of these vasocclusive events is progressive damage to many organs including the kidneys, lungs, and brain. The transfusion of red blood cells (RBC) can ameliorate many of these complications, but can be associated with both acute and chronic complications, including iron overload. The objective of the Best Practices in Transfusion Medicine for Patients with Sickle Cell Disease (SCD) Conference was to review the available published evidence and clinical experience surrounding the use of RBC transfusions for sickle cell disease by a panel of experts. The expert panel developed explicit clinical guidelines for the use of RBC in SCD patients. The panel also made recommendations for further research. A set of guidelines were produced for dissemination to pertinent stakeholders. If implemented, these clinical pathways have the potential to optimize the use of red blood cell transfusions in SCD.

Psychosocial stressors of sickle cell disease on adult patients in Cameroon.

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Wonkam, Ambroise; Mba, Caryl Zameyo; Mbanya, Dora; Ngogang, Jeanne; Ramesar, Raj; Angwafo, Fru F

2014-12-01

Sickle Cell Disease (SCD) is a debilitating illness that affects quality of life. Studies of the psychosocial burden of SCD on patients have been rarely reported in Africa. We used a quantitative method, with face-to-face administered questionnaires, to study indices of psychosocial stressors on adult SCD patients in Cameroon. The questionnaire included a 36-item stress factors scale evaluating general perceptions of stress and five main stressors' domain: disease factors, hospital factors, financial factors, family factors and quality of personal-life factors. Items pertaining to psychosocial stressors involved four response options with increasing severity: 0, 1, 2 or 3. Non-parametric tests were used for analysis. The majority of the 83 participants were urban dwellers, female, 20-30 years old, single, unemployed, with at least a secondary or tertiary education. Median age at diagnosis was 100 months; 47.8% had >3 painful vaso-oclusive crises annually. Only 4.8% had been treated with hydroxyurea. The majority reported moderate to severe difficulty coping with SCD. The "degree of clinical severity" category displayed the highest median score (2.0), while familial stressors showed the lowest (0.8). Being female, married, with low education level, an additional affected sibling and low direct income were significantly associated with specific stressors' categories. In Cameroon, there is an urgent need to implement policies that ensure affordable access to health-care and practices to reduce SCD morbidity and improve patients' quality of life.

Free tissue transfer in patients with sickle cell disease: Considerations for multi-disciplinary peri-operative management.

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Cooper, Lilli; Seth, Rohit; Rhodes, Elizabeth; Alousi, Mohammed; Sivakumar, Bran

2017-01-01

Sickle cell disease (SCD) is an increasingly common condition in the UK. The safety of free tissue transfer in these patients is controversial, and no specific guidelines exist. The aim of this paper is to create recommendations for the plastic surgical multidisciplinary team for use in the assessment and management of SCD patients undergoing free tissue transfer and reconstruction. A literature review was performed in PubMed of 'sickle [TiAb] AND plast* adj3 surg*. Sickle cell disease is explained, as is the relative peri-operative risk in different genotypes of SCD. Acute and chronic manifestations of SCD are described by system, for consideration at pre-operative assessment and post-operative review. The evidence surrounding free tissue transfer and SCD is discussed and the outcomes in published cases summarised. An algorithm for peri-operative multi-disciplinary management is outlined and justified. Free tissue transfer theoretically carries a high risk of a crisis, due not only to long anaesthetic times, but the potential requirement for tourniquet use, and the relatively hypoxic state of the transferred tissue. This paper outlines a useful, practical algorithm to optimise the safety of free tissue transfer in patients with SCD. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Sonographic assessment of spleen size in Saudi patients with sickle cell disease

International Nuclear Information System (INIS)

Al-Salem, Ahmed H.; Al-Aithan, S.; Al-Jama, A.; Al-Dabbous, I.; Bhamidipati, P.

1998-01-01

In patients with SCD, the spleen commonly enlarges during the first two decades of life but then undergoes autosplenectomy due to repeated attacks of vaso-occlusion and infarction. This, however, is not the case in Saudi patients with SCD (340 SCD and 23-sickle beta-thalassemia). A total of 363 patients were evaluated. There ages ranged from 1-60 years (mean 60 years). Only 24 (6.6%) of our patients had autosplenectomy. The splenic index increased with age until about 40 years of age and then gradually decreased indicating persistence of splenomegaly in our patients into an older age group. Forty-three patients (11.8%) had marked-massive splenomegaly (splenic index >120cm) and these had higher HbF levels (mean HbF=22.2%) when compared with those who had autosplenectomy (mean HbF=14.6). This is significant (P-value=0.0169) and confirms the effect of HbF on persistence of splenomegaly in SCD patients. Ultrasonography is a simple, safe and accurate method of assessing splenic size in patients with sickle cell disease. Patients with persistent splenomegaly should be followed closely for development of complications which may necessitate splenectomy. (author)

Dyspnea, pulmonary function and exercise capacity in adult Saudi patients with sickle cell disease

International Nuclear Information System (INIS)

Alameri, Hatem F.; Alem, A.; Al-Momen, A.; Kardas, W.; Owais, M.; Jehangir, A.

2008-01-01

Objective was to examine pulmonary function, dyspnea, and exercise capacity in adult Saudi patients with sickle cell disease (SCD) patients. The patients were recruited from the hematology clinic at King Khalid University Hospital in Riyadh from January to December 2005. The study involved 39 patients with stable SCD 20 women and 19 men, with a mean age of 22.7+/- 7.1 years, hemoglobin level of 95.5+/-14.6g/L and hemoglobin F level of 13.7+/08.6. Patients underwent pulmonary function tests PFT forced expiratory volume in first second [FEV1], forced vital capacity [FVC], and diffusion capacity of carbon monoxide [DLco] data are presented as a percentage of the normal prediction, a 6- minute walk test 6MWT and echocardiography. Dyspnea was assessed using the Borg score. The 6MWT data were compared to body mass index matched healthy controls. Forty-one percent of SCD patients had mild dyspnea at rest and this increased to 61% at the end of the 6MWT. Pulmonary function tests were abnormal in 51%, 36% of patients had a restrictive pattern, 10% had isolated decrease in DLco and 5% had a mixed restrictive-obstrutive pattern. The 6MWD was shorter in SCD patients compared to the controls 368+/-67 versus 407+/-47m, p=0.005. No hematological variables correlated with outcome variables. Chronic pulmonary complications in adult Saudi SCD patients are relatively mild but common. Pulmonary function in these patients differs from that published for African-origin SCD patients. The difference may reflect a different natural history of SCD in the 2 populations. (author)

Validation of the HCM Risk-SCD model in patients with hypertrophic cardiomyopathy following alcohol septal ablation

DEFF Research Database (Denmark)

Liebregts, Max; Faber, Lothar; Jensen, Morten K

2018-01-01

Aims: The HCM Risk-SCD model for prediction of sudden cardiac death (SCD) in hypertrophic cardiomyopathy recommended by the 2014 European Society of Cardiology (ESC) guidelines has not been validated after septal reduction therapy. The aim of this study was to validate the HCM Risk-SCD model...

Quality of life in patients with sickle cell disease in Jamaica: rural-urban differences.

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Asnani, Monika R; Reid, Marvin E; Ali, Susanna B; Lipps, Garth; Williams-Green, Pauline

2008-01-01

Quality of life (QOL) refers to people's ability to function in the ordinary tasks of living. It moves beyond direct manifestations of illness to the patient's personal morbidity. These assessments are an important aspect of chronic disease management. Sickle cell disease (SCD) is a chronic and potentially, quite a debilitating disease. The disease is severe and may result in significant morbidity, as well as a shortened life span. It is the most common genetic disorder seen in Jamaica and impacts on physical, psychological, social and occupational wellbeing. Jamaica is a developing country where support systems that exist for patients with SCD are sparse. Health related QOL has been shown to be poorer in people living in the rural areas as compared with urban populations. Utilization of comprehensive sickle cells disease services has also been shown to be lower for individuals with the disease living in rural areas than for those living in urban areas. As there are rural-urban differences in Jamaica's health services, it is hypothesized that there may be rural-urban differences in the experiences of the disease and the QOL of these patients in these subgroups. The SF 36 v2 (Short Form 36) questionnaire has been validated for use in the Jamaican SCD population. This validated questionnaire was interviewer-administered to 166 patients presenting to an urban clinic for routine health maintenance visits and to 90 patients presenting to the rural clinics for routine visits. Socio-demographic information was also collected on these two groups. Multiple linear regression analyses were performed to study predictors of QOL in these two sub-populations. The study received ethical approval from the University of the West Indies/University Hospital of the West Indies Ethics Committee. There were no significant differences in the measured socio-demographic characteristics of the rural and urban patients. Living in rural areas compared with urban areas (p <0.001), being

[The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

Science.gov (United States)

Yang, Jian-Lin; Hao, Hong-Jun; Qin, Bin; Bang, Ling-Qing; Zhang, Zhi-Hong; Xin, Dian-Qi; Guo, Ying-Lu; Na, Yan-Qun

2005-03-16

To study the relationship between the sCD30 and acute rejection. We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.

Hematopoietic stem cell transplantation in sickle cell disease: patient selection and special considerations

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Bhatia M

2015-07-01

Full Text Available Monica Bhatia,1 Sujit Sheth21Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Medical Center, 2Division of Pediatric Hematology and Oncology, Weill Cornell Medical College, New York, NY, USAAbstract: Hematopoietic stem cell transplantation remains the only curative treatment currently in use for patients with sickle cell disease (SCD. The first successful hematopoietic stem cell transplantation was performed in 1984. To date, approximately 1,200 transplants have been reported. Given the high prevalence of this disorder in Africa, and its emergence in the developed world through immigration, this number is relatively small. There are many reasons for this; primary among them are the availability of a donor, the risks associated with this complex procedure, and the cost and availability of resources in the developing world. Of these, it is fair to say that the risks associated with the procedure have steadily decreased to the point where, if currently performed in a center with experience using a matched sibling donor, overall survival is close to 100% and event-free survival is over 90%. While there is little controversy around offering hematopoietic stem cell transplantation to symptomatic SCD patients with a matched sibling donor, there is much debate surrounding the use of this modality in “less severe” patients. An overview of the current state of our understanding of the pathology and treatment of SCD is important to show that our current strategy is not having the desired impact on survival of homozygous SCD patients, and should be changed to significantly impact the small proportion of these patients who have matched siblings and could be cured, especially those without overt clinical manifestations. Both patient families and providers must be made to understand the progressive nature of SCD, and should be encouraged to screen full siblings of patients with homozygous SCD for their potential to

Clinical Interpretation of Quantitative Sensory Testing as a Measure of Pain Sensitivity in Patients with Sickle Cell Disease

OpenAIRE

Brandow, Amanda M.; Panepinto, Julie A.

2016-01-01

Patients with sickle cell disease (SCD) display significantly lower mean/median thermal and mechanical pain thresholds compared to controls. This suggests impaired pain sensitivity where stimuli produce exaggerated pain. Despite these mean/median differences, clinicians need to understand if patients meet criteria for impaired pain sensitivity. We defined thresholds for impaired cold, heat, and mechanical pain sensitivity in SCD patients. Using quantitative sensory testing (QST) we assessed c...

Elevated soluble CD163 plasma levels are associated with disease severity in patients with hemorrhagic fever with renal syndrome.

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Junning Wang

Full Text Available Hantaan virus is a major zoonotic pathogen that causesing hemorrhagic fever with renal syndrome (HFRS. Although HFRS pathogenesis has not been entirely elucidated, the importance of host-related immune responses in HFRS pathogenesis has been widely recognized. CD163, a monocyte and macrophage-specific scavenger receptor that plays a vital function in the hosts can reduce inflammation, is shed during activation as soluble CD163 (sCD163. The aim of this study was to investigate the pathological significance of sCD163 in patients with HFRS.Blood samples were collected from 81 hospitalized patients in Tangdu Hospital from October 2011 to January 2014 and from 15 healthy controls. The sCD163 plasma levels were measured using a sandwich ELISA, and the relationship between sCD163 and disease severity was analyzed. Furthermore, CD163 expression in 3 monocytes subset was analyzed by flow cytometry.The results demonstrated that sCD163 plasma levels during the HFRS acute phase were significantly higher in patients than during the convalescent stage and the levels in the healthy controls (P<0.0001. The sCD163 plasma levels in the severe/critical group were higher than those in the mild/moderate group during the acute (P<0.0001. A Spearman correlation analysis indicated that the sCD163 levels were positively correlated with white blood cell, serum creatine, blood urea nitrogen levels, while they were negatively correlated with blood platelet levels in the HFRS patients. The monocyte subsets were significantly altered during the acute stage. Though the CD163 expression levels within the monocyte subsets were increased during the acute stage, the highest CD163 expression level was observed in the CD14++CD16+ monocytes when compared with the other monocyte subsets.sCD163 may be correlated with disease severity and the disease progression in HFRS patients; however, the underlying mechanisms should be explored further.

Addiction or pseudoaddiction in sickle cell disease patients: Time to ...

African Journals Online (AJOL)

Objective: The objective of this report is to highlight the background factors associated with opioid abuse among Sickle Cell Disease (SCD) patients. Patients: Eleven patients aged 13-53 years (mean, 26.1yrs) which included six female and five male were seen in the last six year at a tertiary health facility. The modes of ...

Impact of skin capsular distance on the performance of controlled attenuation parameter in patients with chronic liver disease.

Science.gov (United States)

Shen, Feng; Zheng, Rui-Dan; Shi, Jun-Ping; Mi, Yu-Qiang; Chen, Guo-Feng; Hu, Xiqi; Liu, Yong-Gang; Wang, Xiao-Ying; Pan, Qin; Chen, Guang-Yu; Chen, Jian-Neng; Xu, Liang; Zhang, Rui-Nan; Xu, Lei-Ming; Fan, Jian-Gao

2015-11-01

Controlled attenuation parameter (CAP) is a non-invasive method for evaluating hepatic steatosis. However, larger skin capsular distance (SCD) can affect the accuracy. The aim of this study was to investigate the impact of SCD on the diagnostic performance of CAP and liver stiffness measurement (LSM). Of 101 patients with non-alcoholic fatty liver disease (NAFLD) and 280 patients with chronic hepatitis B (CHB) who underwent liver biopsy were prospectively recruited. CAP, LSM and SCD were performed using FibroScan with M probe. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy. The optimal thresholds were defined by the maximum Youden index. SCD (B 30.34, P 33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD 33% and >66% were 255.0 dB/m, 283.5 dB/m and 293.5 dB/m. However, cut-offs were elevated by approximately 60-70 dB/m for SCD ≥25 mm. When stratified by fibrosis grade, LSM was significantly affected by SCD ≥25 mm for advanced fibrosis (≥F3) in NAFLD, but not in CHB. CAP is a promising tool for detecting and quantifying hepatic steatosis. SCD ≥25 mm may cause overestimation of steatosis. Similarly, SCD ≥25 mm affects the detection of advanced fibrosis by LSM in NAFLD patients. © 2015 The Authors. Liver International Published by John Wiley & Sons Ltd.

Anti-HI can cause a severe delayed hemolytic transfusion reaction with hyperhemolysis in sickle cell disease patients.

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Ibanez, Clara; Habibi, Anoosha; Mekontso-Dessap, Armand; Chadebech, Philippe; Chami, Btissam; Bierling, Philippe; Galactéros, Frédéric; Rieux, Claire; Nataf, Joëlle; Bartolucci, Pablo; Peyrard, Thierry; Pirenne, France

2016-07-01

Delayed hemolytic transfusion reaction (DHTR) is a life-threatening condition in sickle cell disease (SCD) patients that is frequently complicated by hyperhemolysis. Antibodies resulting from antigen disparity between donors of European ancestry and patients of African ancestry are common, but situations involving antibodies not classically of clinical significance are also encountered. Anti-HI is generally considered to be an innocuous naturally occurring antibody. We describe two cases of hyperhemolysis with anti-HI and provide details of the reported cases. Both SCD patients were polyimmunized and belonged to blood group B. They developed anti-HI that was reactive at 37°C, after the transfusion of group O red blood cell units matched for all known and produced antibodies classically considered to be clinically significant. Both patients developed DHTR with hyperhemolysis. In the first case, a pregnant woman, a second transfusion was unavoidable and the patient died from cardiac arrest. The state of the second patient improved without the need for further transfusion. Three other cases of DHTR with anti-HI have been described in the literature in SCD patients. The two additional cases reported here definitively demonstrate that anti-HI is dangerous in SCD patients. As a result, ABO-identical matching (including A1 status) must be considered in SCD patients with anti-HI. © 2016 AABB.

Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype

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A. Hannemann

2015-11-01

Full Text Available Sickle cell disease (SCD in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals — but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

Osteoporosis and Vitamin D Deficiency in Patients with Sickle Cell Disease

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Zeynep Ozdemir

2016-07-01

Full Text Available Aim: Bone disorders such as osteopenia or osteoporosis are the most common clinical manifestations seen in sickle cell disease (SCD with a high of morbidity. There are many reasons, including vitamin D deficiency for the appearance of bone problems. In the present study we aimed to evaluate osteopathy in patients with SCD using bone mineral densitometry (BMD and biochemical indices. Material and Method: 61 patients (29 female, 32 male were included in the study. The age, gender, and biochemical parameters with BMD were evaluated using dual energy X-ray absorptiometry from lumbar vertebrae. According to Z scores, [-2] was considered as osteoporosis. Multivariate analysis was performed to determine the factors influencing BMD. Results: There were a total of 61 SCD patients. The average age was 21.06±5.06 (15-27 years and the mean BMI was 19.15±2.98 kg/m2. 23 patients were osteopenic (11 female, 12 male (37.7% and 26 were osteoporotic (12 female, 13 male (44.3%. Twelve patients (6 female and 6 male (18% had normal Z scores. Vitamin D was found severely deficient (

Posttransplant sCD30 as a biomarker to predict kidney graft outcome.

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Süsal, Caner; Opelz, Gerhard

2012-09-08

In current clinical praxis, monitoring of immunosuppressive agents in organ transplantation is restricted to measurement of drug blood levels and does not consider the drug's variable effect on the individual patient's immune system. Establishment of biological markers that measure the biological effect of immunosuppressive drugs is desirable and would enable the identification of patients who are at risk of developing rejection, or patients who are suitable for minimization or weaning of immunosuppressive therapy. Several studies demonstrated that the technically simple posttransplant measurement in serum of the T cell activation marker soluble CD30 (sCD30) allows prediction of subsequent graft loss in kidney transplant recipients. sCD30 is a relatively large molecule and therefore an attractive biological marker which is resistant to repeated thawing cycles and temperature differences and easily determined using commercial ELISA. Whether sCD30-based prospective adjustment of immunosuppressive therapy can prevent irreversible graft damage and improve long-term graft outcome awaits evaluation in randomized controlled trials. Copyright © 2011 Elsevier B.V. All rights reserved.

The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

DEFF Research Database (Denmark)

Sandahl, T D; McGrail, R; Møller, H J

2016-01-01

BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can...... predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test...... the predictive accuracy we developed a CD163-fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant. RESULTS: Both sCD163 and the ELF components increased in a stepwise manner...

Relevance of blood groups in transfusion of sickle cell disease patients.

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Noizat-Pirenne, France

2013-03-01

Blood groups are clinically significant in sickle cell disease (SCD) as transfusion remains a key treatment in this pathology. The occurrence of a delayed haemolytic transfusion reaction (DHTR) is not rare and is a life-threatening event. The main cause of DHTR is the production of alloantibodies against red blood cell antigens. The high rate of alloimmunization in SCD patients is mainly due to the differences of red blood groups between patients of African descent, and the frequently Caucasian donors. From an immuno-haematological point of view, DHTR in SCD patients has specific features: classical antibodies known to be haemolytic can be encountered, but otherwise non significant antibodies, autoantibodies and antibodies related to partial and rare blood groups are also frequently found in individuals of African descent. In some cases, there are no detectable antibodies. As alloimmunization remains the main cause of DHTR, it is extremely important to promote blood donation by individuals of African ancestry to make appropriate blood available. Copyright © 2012 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Plasma sCD14 as a biomarker to predict pulmonary exacerbations in cystic fibrosis.

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Bradley S Quon

Full Text Available BACKGROUND: One in four cystic fibrosis (CF patients diagnosed with a pulmonary exacerbation will not recover their baseline lung function despite standard treatment. This highlights the importance of preventing such events. Clinical decision-making can be improved through a simple blood test that predicts individuals at elevated short-term risk of an exacerbation. METHODS: We obtained plasma samples from 30 stable CF patients from the St. Paul's Hospital Adult CF Clinic (Vancouver, Canada. For 15 patients, an additional plasma sample was obtained during an exacerbation. Soluble CD14 (sCD14 and C-reactive protein (CRP were quantified using ELISA kits. Myeloperoxidase (MPO, interleukin(IL-6, IL-1β, monocyte chemoattractant protein-1 (MCP-1, vascular endothelial growth factor (VEGF, and granulocyte colony-stimulating factor (G-CSF were quantified using Luminex™ immunoassays. Stable state biomarker levels were examined in their ability to predict individuals that would experience a pulmonary exacerbation requiring intravenous (IV antibiotics within 4 months. Paired stable and exacerbation plasma biomarker levels were also compared. RESULTS: sCD14 levels were significantly higher in patients that experienced a pulmonary exacerbation requiring IV antibiotics within 4 months (p = 0.001. sCD14 cut-off value of 1450 ng/mL was associated with an area under the curve of 0.91 (95% CI 0.83-0.99 for predicting an exacerbation within 4 months of a stable visit, with a sensitivity of 100% and specificity of 82%. Plasma sCD14 levels were significantly higher during exacerbations than during periods of clinical stability (p = 0.03. CONCLUSIONS: Plasma sCD14 is a promising biomarker for identifying CF patients who will exacerbate within 4 months of a stable visit but requires further study in larger, independent cohorts.

Elevated stearoyl-CoA desaturase in brains of patients with Alzheimer's disease.

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Giuseppe Astarita

Full Text Available The molecular bases of Alzheimer's disease (AD remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37 compared to age-matched controls (N = 17. The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs and mead acid (20:3n-9 in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b, were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio ('desaturation index'--displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = -0.80; P = 0.0001 and the Boston Naming test (r = -0.57; P = 0.0071. Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD.

Macrophage activation marker soluble CD163 and non-alcoholic fatty liver disease in morbidly obese patients undergoing bariatric surgery

DEFF Research Database (Denmark)

Kazankov, Konstantin; Tordjman, Joan; Møller, Holger Jon

2015-01-01

BACKGROUND AND AIMS: Macrophages play an important role in non-alcoholic fatty liver disease (NAFLD). Soluble CD163 (sCD163) is a specific marker of macrophage activation. We aimed to measure sCD163 in morbidly obese patients with varying degrees of NAFLD before and after bariatric surgery (BS...... (NAS), Kleiner fibrosis score, and the fatty liver inhibition of progression (FLIP) algorithm. In a subset, CD163 immunohistochemistry and real-time quantitative polymerase chain reaction for CD163 mRNA were performed. RESULTS: sCD163 was higher in patients with NAS ≥ 5 compared with those with NAS ...). METHODS: Demographic, clinical, and biochemical data, and plasma sCD163 measured by enzyme-linked immunosorbent assay, of 196 patients were collected preoperatively and 3, 6, and 12 months after BS leading to significant weight loss. Peroperative liver biopsies were assessed for the NAFLD Activity Score...

INCREASED VASOOCCLUSIVE CRISIS IN “O” BLOOD GROUP SICKLE CELL DISEASE PATIENTS: ASSOCIATION WITH UNDERLYING THROMBOSPONDIN LEVELS.

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M. Al Huneini

2017-04-01

Full Text Available Abstract: Objectives: To explore the incidence of vaso-occlusive crisis (VOC in Blood Group “O” sickle cell disease (SCD patients, and correlate it with the blood group and thrombospondin (TSP levels. Methods: In 89 consecutive SCD patients, blood samples were obtained for vWF antigen, collagen binding activity, blood group typing, C-reactive protein, variant hemoglobin analysis (HPLC, Serum TSP 1 and TSP 2 levels, complete blood counts, liver function tests, LDH and renal function tests during VOC episodes and in steady state conditions. Results: In the steady state SCD patients (n=72, “O” blood group patients (n=37 showed significantly higher median serum TSP 1 and TSP 2 levels than the non “O” blood group patients [n=35] [p <0.05, Mann-Whitney test], with an inverse relation between VWF:Ag, Factor VIII:C and TSP levels. Furthermore, the serum TSP 1 and TSP 2 levels were significantly higher in patients presenting with acute VOC [n=17], and in those with repeated VOC’s (group 1, n=16 especially amongst those patients with blood group “O” [p, <0.05, Mann-Whitney test]. Conclusions: The study shows that there was an inverse relation between TSP and vWF levels, in blood group “O” SCD patients with an upregulation of the TSP levels. Expectedly, during active VOC crisis, the TSP 1 and TSP 2 levels were significantly elevated.    Key Words: VOC; SCD; TSP; vWD; Blood groups

Extent of silent cerebral infarcts in adult sickle-cell disease patients on magnetic resonance imaging: is there a correlation with the clinical severity of disease?

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Ekaterini Solomou

2013-02-01

Full Text Available The aim of this paper is to correlate the extent of silent cerebral infarcts (SCIs on magnetic resonance imaging (MRI with the clinical severity of sickle cell disease (SCD in adult patients. Twenty-four consecutive adult asymptomatic SCD patients (11 male and 13 female with a mean age of 38.4 years (range 20-59 were submitted to brain MRI on a 1 Tesla Gyroscan Intera, Philips MR scanner with a dedicated head coil. The protocol consisted of TSE T2-weighted and FLAIR images on the axial and coronal planes. MRI readings were undertaken by two radiologists and consensus readings. Patients were compound heterozygotes (HbS/β-thal. The extent of SCIs was classified from 0-2 with 0 designating no lesions. Clinical severity was graded as 0-2 by the hematologist, according to the frequency and severity of vaso-occlusive crises. There was no statistically significant correlation between the severity of clinical disease and the extent of SCIs on MR imaging. The extent of SCI lesions did not differ statistically between younger and older patients. Patients receiving hydroxyurea had no statistically significant difference in the extent of SCI lesions. The extent of SCIs in heterozygous (HbS/β-thal SCD patients is not age related and may be quite severe even in younger (<38.4 years patients. However the extent of SCIs is not correlated with the severity of clinical disease.

Serological markers of enterocyte damage and apoptosis in patients with celiac disease, autoimmune diabetes mellitus and diabetes mellitus type 2.

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Hoffmanová, I; Sánchez, D; Hábová, V; Anděl, M; Tučková, L; Tlaskalová-Hogenová, H

2015-01-01

Impairment of mucosal barrier integrity of small intestine might be causative in immune-mediated gastrointestinal diseases. We tested the markers of epithelial apoptosis - cytokeratin 18 caspase-cleaved fragment (cCK-18), and enterocyte damage - intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14) in sera of patients with untreated celiac disease (CLD), those on gluten-free diet (CLD-GFD), patients with autoimmune diabetes mellitus (T1D), T1D with insulitis (T1D/INS), and diabetes mellitus type 2 (T2D). We found elevated levels of cCK-18 (PCLD when compared to healthy controls. However, the levels of cCK-18 (PCLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (PCLD patients were seropositive for cCK-18, 19/43 for I-FABP and 11/43 for sCD14; 9/30 of T2D patients were positive for cCK-18 and 5/20 of T1D/INS for sCD14, while in controls only 3/41 were positive for cCK-18, 3/41 for I-FABP and 1/41 for sCD14. We documented for the first time seropositivity for sCD14 in CLD and potential usefulness of serum cCK-18 and I-FABP as markers of gut damage in CLD, CLD-GFD, and diabetes.

Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management.

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Nur, Erfan; Biemond, Bart J; Otten, Hans-Martin; Brandjes, Dees P; Schnog, John-John B

2011-06-01

Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management. Copyright © 2011 Wiley-Liss, Inc.

Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

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Ephraim, Richard K D; Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement

2016-01-01

Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) ( p = 0.001) and high-density lipoprotein cholesterol (HDL-C) ( p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

Quantitative sensory testing and pain-evoked cytokine reactivity: comparison of patients with sickle cell disease to healthy matched controls.

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Campbell, Claudia M; Carroll, C Patrick; Kiley, Kasey; Han, Dingfen; Haywood, Carlton; Lanzkron, Sophie; Swedberg, Lauren; Edwards, Robert R; Page, Gayle G; Haythornthwaite, Jennifer A

2016-04-01

Sickle cell disease (SCD) is an inherited blood disorder associated with significant morbidity, which includes severe episodic pain, and, often, chronic pain. Compared to healthy individuals, patients with SCD report enhanced sensitivity to thermal detection and pain thresholds and have altered inflammatory profiles, yet no studies to date have examined biomarker reactivity after laboratory-induced pain. We sought to examine this relationship in patients with SCD compared to healthy control participants. We completed quantitative sensory testing in 83 patients with SCD and sequential blood sampling in 27 of them, whom we matched (sex, age, race, body mass index, and education) to 27 healthy controls. Surprisingly, few quantitative sensory testing differences emerged between groups. Heat pain tolerance, pressure pain threshold at the trapezius, thumb, and quadriceps, and thermal temporal summation at 45°C differed between groups in the expected direction, whereas conditioned pain modulation and pain ratings to hot water hand immersion were counterintuitive, possibly because of tailoring the water temperature to a perceptual level; patients with SCD received milder temperatures. In the matched subsample, group differences and group-by-time interactions were observed in biomarkers including tumor necrosis factor alpha, interleukin-1ß, interleukin-4, and neuropeptide Y. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Our findings suggest amplified pain-evoked proinflammatory cytokine reactivity among patients with SCD relative to carefully matched controls. Future research is warranted to evaluate the impact of enhanced pain-related cytokine response and whether it is predictive of clinical characteristics and the frequency/severity of pain crises in patients with SCD.

Mortality rate in Sickle Cell Disease Patients in Crisis at a ...

African Journals Online (AJOL)

The Haematology Day Care Unit (HDCU) of the University College Hospital, Ibadan, Nigeria was established in 1975 with the main goal of providing immediate and specialized care to haematological emergencies, particularly sickle cell disease (SCD) patients. Since inception, a systematic analysis of its effectiveness has ...

Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy.

Science.gov (United States)

ElAlfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman ElSayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

2018-06-20

Sickle cell disease (SCD) is associated with alterations in immune phenotypes. CD4 + CD28 null T lymphocytes have pro-inflammatory functions and are linked to vascular diseases. To assess the percentage of CD4 + CD28 null T lymphocytes, natural killer cells (NK), and IFN-gamma levels, we compared 40 children and adolescents with SCD with 40 healthy controls and evaluated their relation to disease severity and response to therapy. Patients with SCD steady state were studied, focusing on history of frequent vaso-occlusive crisis, hydroxyurea therapy, and IFN-gamma levels. Analysis of CD4 + CD28 null T lymphocytes and NK cells was done by flow cytometry. Liver and cardiac iron overload were assessed. CD4 + CD28 null T lymphocytes, NK cells, and IFN-gamma levels were significantly higher in patients than controls. Patients with history of frequent vaso-occlusive crisis and those with vascular complications had higher percentage of CD4 + CD28 null T lymphocytes and IFN-gamma while levels were significantly lower among hydroxyurea-treated patients. CD4 + CD28 null T lymphocytes were positively correlated to transfusional iron input while these cells and IFN-gamma were negatively correlated to cardiac T2* and duration of hydroxyurea therapy. NK cells were correlated to HbS and indirect bilirubin. Increased expression of CD4 + CD28 null T lymphocytes highlights their role in immune dysfunction and pathophysiology of SCD complications.

Cranial involvement in sickle cell disease

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Alkan, Ozlem, E-mail: yalinozlem@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Ebru, E-mail: ebru90@yahoo.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Osman, E-mail: ebos90@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yildirim, Tulin, E-mail: ytulin@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Karaca, Sibel, E-mail: sibelkaraca@hotmail.com [Department of Neurology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yeral, Mahmut, E-mail: mahmutyeral@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kasar, Mutlu, E-mail: mutlukasar@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Ozdogu, Hakan, E-mail: hakanozdogu@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey)

2010-11-15

Purpose: To evaluate cranial findings in patients with neurologically symptomatic sickle cell disease (SCD). Materials and methods: We studied 50 consecutive patients with SCD and neurologic symptoms. All patients underwent brain MR examinations: all 50 underwent classic MR imaging; 42, diffusion-weighted MR imaging; 10, MR angiography; four, MR venography; and three patients, digital subtraction angiography. Results: Of the 50 SCD patients, 19 (38%) had normal MR findings, and 31 (62%) showed abnormalities on brain MR images. Of the 50 patients, 16 (32%) had ischemic lesions; two (4%), subarachnoid hemorrhage; one (2%), moya-moya pattern; one (2%), posterior reversible encephalopathy; one (2%), dural venous sinus thrombosis; 12 (24%), low marrow signal intensity and thickness of the diploic space; 12 (24%), cerebral atrophy; and two (4%), osteomyelitis. Twenty-seven patients (54%) presented with headache, which was the most common clinical finding. Conclusions: The cranial involvement is one of the most devastating complications of SCD. Early and accurate diagnosis is important in the management of cranial complications of SCD.

Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography

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Verlhac, S. [Service de Radiologie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Bernaudin, F. [Service de Pediatrie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Tortrat, D. [Association Claude Bernard, 75 - Paris (France); Brugieres, P. [Service de Neuroradiologie, Hopital Henri Mondor, 94 - Creteil (France); Mage, K. [Service de Radiologie, Centre Hospitalier Intercommunal, 94 - Creteil (France); Gaston, A. [Service de Neuroradiologie, Hopital Henri Mondor, 94 - Creteil (France); Reinert, P. [Service de Pediatrie, Centre Hospitalier Intercommunal, 94 - Creteil (France)

1995-11-01

A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes. (orig.)

Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography

International Nuclear Information System (INIS)

Verlhac, S.; Bernaudin, F.; Tortrat, D.; Brugieres, P.; Mage, K.; Gaston, A.; Reinert, P.

1995-01-01

A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes. (orig.)

Socio-demographic characteristics and psychosocial consequences of sickle cell disease: the case of patients in a public hospital in Ghana.

Science.gov (United States)

Adzika, Vincent A; Glozah, Franklin N; Ayim-Aboagye, Desmond; Ahorlu, Collins S K

2017-01-31

Sickle cell disease (SCD) is of major public health concern globally, with majority of patients living in Africa. Despite its relevance, there is a dearth of research to determine the socio-demographic distribution and psychosocial impact of SCD in Ghana. The objective of this study was to examine the socio-demographic distribution and psychosocial consequences of SCD among patients in Ghana and to assess their quality of life and coping mechanisms. A cross-sectional research design was used that involved the completion of questionnaires on socio-demographic characteristics, quality of life, coping mechanisms, anxiety and depression. Participants were 387 male and female patients attending a sickle cell clinic in a public hospital. Results showed that majority of the patients were single, female, less than 39 years old and had attained secondary school level of education or less. Also, patients were more satisfied by the presence of love, friends and relatives as well as home, community and neighbourhood environment. While pains of varied nature and severity were the major reasons for attending hospital in SCD condition, going to the hospital as well as having faith in God was the most frequently reported mechanisms for coping with an unbearable SCD attacks. Results of multiple regression analysis showed that some socio-demographic and quality of life indicators had strong associations with anxiety and/or depression. It is recommended that a holistic intervention strategy incorporating psychosocial dimensions should be considered in the treatment and management of SCD.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation.

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Fernández-Ruiz, Mario; Parra, Patricia; López-Medrano, Francisco; Ruiz-Merlo, Tamara; González, Esther; Polanco, Natalia; Origüen, Julia; San Juan, Rafael; Andrés, Amado; Aguado, José María

2017-04-01

The transmembrane glycoprotein CD30 contributes to regulate the balance between Th 1 and Th 2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post-transplant infection. Serum sCD30 was measured by a commercial ELISA assay at baseline and post-transplant months 1, 3, and 6 in 100 kidney transplant (KT) recipients (279 monitoring points). The impact of sCD30 levels on the incidence of overall, bacterial and opportunistic infection during the first 12 months after transplantation was assessed by Cox regression. There were no differences in serum sCD30 according to the occurrence of overall or opportunistic infection. However, sCD30 levels were higher in patients with bacterial infection compared to those without at baseline (P=.038) and months 1 (Ptransplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; PsCD30 levels ≥13.5 ng/mL remained as an independent risk factor for bacterial infection (adjusted hazard ratio [aHR]: 4.65; 95% confidence interval [CI]: 2.05-10.53; sCD30 levels ≥6.0 ng/mL at month 1 acted as a risk factor for subsequent bacterial infection (aHR: 5.29; 95% CI: 1.11-25.14; P=.036). Higher serum sCD30 levels were associated with an increased risk of bacterial infection after KT. We hypothesize that this biomarker reflects a Th 2 -polarized T-cell response, which exerts a detrimental effect on the immunity against bacterial pathogens. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Attitudes toward Management of Sickle Cell Disease and Its Complications: A National Survey of Academic Family Physicians

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Arch G. Mainous

2015-01-01

Full Text Available Objective. Sickle cell disease (SCD is a disease that requires a significant degree of medical intervention, and family physicians are one potential provider of care for patients who do not have access to specialists. The extent to which family physicians are comfortable with the treatment of and concerned about potential complications of SCD among their patients is unclear. Our purpose was to examine family physician’s attitudes toward SCD management. Methods. Data was collected as part of the Council of Academic Family Medicine Educational Research Alliance (CERA survey in the United States and Canada that targeted family physicians who were members of CERA-affiliated organizations. We examined attitudes regarding management of SCD. Results. Overall, 20.4% of respondents felt comfortable with treatment of SCD. There were significant differences in comfort level for treatment of SCD patients depending on whether or not physicians had patients who had SCD, as well as physicians who had more than 10% African American patients. Physicians also felt that clinical decision support (CDS tools would be useful for treatment (69.4% and avoiding complications (72.6% in managing SCD patients. Conclusions. Family physicians are generally uncomfortable with managing SCD patients and recognize the utility of CDS tools in managing patients.

[Blood transfusion assessment to 112 homozygous sickle-cell disease patients in university hospital of Brazzaville].

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Dokekias, A Elira; Ossini, L Ngolet; Tsiba, F O Atipo; Malanda, F; Koko, I; De Montalembert, M

2009-01-01

Homozygous, sickle-cell disease (SCD) is responsible for acute complication, especially anaemic crisis and special situation such as acute chest syndrome, stroke and acute priapism. Pregnancy sickle-cell disease presents high risk for the mother and the fetus. In these indications, blood transfusion is the main therapy aiming to reduce anaemia in order to restore hemoglobin's rate or to increase normal Hb proportion. This study aims to assess the short-term efficiency of the red cell transfusion in SCD homozygous form. One hundred and twelve homozygous sickle-cell patients were enrolled in this prospective study: 59 females and 53 males, median age is 21,8 years (extremes: 2 and 45 years). These patients are mostly with very low income. Two groups of patients are included in this study. In the first group, patients present acute anemia crisis caused by infections disease (malaria, bacterial infections). In the second group (20 cases), SCD patients have particularly situations: pregnancy (10 cases); stroke (six cases); cardiac failure (two cases) and priapism (two cases). Transfusion treatment in first group is simple regimen. Transfusion of EC increased median Hb level at 2,9 g/dl (extremes: 1,1 and 4,7). In the second group of patients, 16 cases were transfused by manual partial exchange (1-3) and four patients received simple regimen of transfusion. Median Hb level was 3,1g/dl (extremes: 2,4-4,9 g/dl). HbS percentage reduction was after PTE between -30 and -66,8% (median: -52,6%). According to our diagnostic possibilities (blood serologic test), we have not found any contamination by HIV, HBV and HCV (virus).

The super sickling haemoglobin HbS-Oman: a study of red cell sickling, K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS-Oman (HbA/S-Oman genotype).

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Al Balushi, Halima W M; Wali, Yasser; Al Awadi, Maha; Al-Subhi, Taimoora; Rees, David C; Brewin, John N; Hannemann, Anke; Gibson, John S

2017-10-01

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K + permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K + was markedly abnormal with elevated activities of P sickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca 2+ entry and Mg 2+ loss via P sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K + transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype. © 2017 John Wiley & Sons Ltd.

Monocyte expression and soluble levels of the haemoglobin receptor (CD163/sCD163 and the mannose receptor (MR/sMR in septic and critically ill non-septic ICU patients.

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Anders G Kjærgaard

Full Text Available BACKGROUND: The diagnosis of sepsis is challenging and there is an unmet need for sensitive and specific diagnostic and prognostic biomarkers. Following activation of macrophages and monocytes, the haptoglobin-haemoglobin receptor (CD163 and the mannose receptor (MR are shed into the circulation (sCD163 and sMR. OBJECTIVE: We investigated monocyte expression of CD163 and MR, and levels of sCD163 and sMR in septic and non-septic patients, and in healthy controls. We hypothesised that these receptors are elevated during sepsis and can be used diagnostic and prognostic. METHODS: Twenty-one patients with severe sepsis or septic shock and 15 critically ill non-septic patients were included in this prospective observational study at three ICUs at Aarhus University Hospital and Randers Regional Hospital, Denmark. Fifteen age- and gender-matched healthy volunteers served as controls. Levels of sCD163 and sMR were measured using a sandwich ELISA and monocyte expression of CD163 and MR was evaluated by flow cytometry during the first four days of ICU stay. The diagnostic and prognostic values of the receptors were assessed using AUROC curves. RESULTS: At ICU admission and during the observation period, monocyte expression of CD163 and levels of sCD163 and sMR were significantly higher in septic patients compared with non-septic patients and healthy controls (p<0.01 for all comparisons. Monocytes did not express MR. The diagnostic values estimated by AUROC were 1.00 for sMR, 0.95 for sCD163, 0.87 for CRP, and 0.75 for monocyte-bound CD163. Among the septic patients, monocyte expression of CD163 was higher in non-survivors compared with survivors at ICU admission (p = 0.02 and during the observation period (p = 0.006. The prognostic value of monocyte-bound CD163 estimated by AUROC at ICU admission was 0.82. CONCLUSION: The macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease.

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Strong, Heather; Mitchell, Monica J; Goldstein-Leever, Alana; Shook, Lisa; Malik, Punam; Crosby, Lori E

2017-08-01

Sickle cell disease (SCD) is a chronic genetic disease with high morbidity and early mortality; it affects nearly 100,000 individuals in the USA. Bone marrow transplantation, the only curative treatment, is available to less than 20% of patients because of a number of access barriers. Gene transfer therapy (GTT) has been shown to be curative in animal models and is approved for use in humans for early-phase studies at a few centers. GTT would offer a more accessible treatment option available to all patients. It is important to understand patient perspectives on GTT to help ensure human clinical trial success. Two focus groups were conducted with younger (18-30 years) and older (31 years and older) adults with SCD to obtain data on patient knowledge and beliefs about GTT. Data from these two focus groups was used to develop a GTT educational brochure. A third focus group was conducted to obtain participant feedback on acceptability and feasibility of education and the brochure. Most adults, especially young adults, had little knowledge about GTT and expressed fear and uncertainty about the side effects of chemotherapy (e.g., hair loss, infertility), use of a human immunodeficiency virus (HIV)-derived viral vector, and potential for cancer risk. Participants wanted full transparency in educational materials, but advised researchers not to share the vector's relation to HIV because of cultural stigma and no HIV virus is used for the GTT vector. Older adults had more desire to participate in human clinical GTT trials than younger participants. When recruiting for trials, researchers should develop GTT educational materials that address participant lack of trust in the healthcare system, cultural beliefs, fears related to side effects, and include visual illustrations. Use of such materials will provide adults with SCD the information they need to fully evaluate GTT.

Post-transplant increased levels of serum sCD30 is a marker for prediction of kidney allograft loss in a 5-year prospective study.

Science.gov (United States)

Delgado, Julio C; Pavlov, Igor Y; Shihab, Fuad S

2009-12-01

Levels of sCD30 represent a biomarker for early outcome in kidney transplantation. The purpose of this study was to determine the role of sCD30 levels for prediction of graft loss in the late post-transplant period. Sera were collected immediately pre-transplant and yearly thereafter for up to 5-year post-transplant in 37 primary renal transplant recipients. Levels of serum sCD30 were tested using a fluorescent microsphere assay. Levels of sCD30 significantly decreased after transplantation and remained normal in 34 patients without graft loss up to 5-year post-transplant. Elevated levels of serum sCD30 preceded the increase of serum creatinine in patients with subsequent graft loss. Elevated levels of serum sCD30 post-transplant might be a marker for predicting subsequent graft loss in the post-transplant period.

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.

Science.gov (United States)

Allen Liles, Edmund; Kirsch, Jonathan; Gilchrist, Michael; Adem, Mukhtar

2014-04-01

Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care. Our study sought to evaluate the development and implementation of a care pathway for patients with SCD experiencing VOCs. The University of North Carolina (UNC) Comprehensive Sickle Cell Program provides all levels of care for a large population of patients with sickle cell anemia. All patients admitted to UNC Hospitals with SCD VOCs from January 2009 through June 2011 were evaluated. During this time period, we also assessed sequential prospective cohorts during progressive phases of developing and implementing a quality improvement and pathway of care program for this patient population in our study. The developed pathway entailed geographic localization for VOC patients, a single group of faculty physicians caring for these patients, and early use of patient-controlled analgesia (PCA) to achieve pain control. Physicians from the UNC Hospital Medicine Program were responsible for the initiatives. Cohorts were compared to a baseline historical control. Outcomes of interest included patient length of stay (LOS) in the hospital, 30-day readmission rate, need for transfusion, incidence of acute chest syndrome, use of naloxone, and use of PCA. Compared with an historical baseline cohort, the development and implementation of a VOC care pathway for patients with SCD led to reduction in average hospital LOS by 1.44 days (P management of patients with SCD VOCs using a care pathway that emphasizes early, aggressive PCA-based pain control is associated with reduced hospital LOS. The LOS reduction seen in our study is clinically meaningful. Notably, other measures of patient outcomes and quality of care metrics did not change significantly, and some trended towards improvement.

Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

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Viviano Enza

2010-10-01

Full Text Available Abstract Background To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS among people infected with KS-associated herpesvirus (KSHV. Methods In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1 and viral capsid antigen (anti-VCA. Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods. Results Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07 and anti-VCA (P = 0.0001 - 0.03. Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03, and they were marginally lower with older age and cortisone use (Padj ≤ 0.09. Conclusions Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.

Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease

OpenAIRE

Summarell, Carly C Ginter; Sheehan, Vivien A

2016-01-01

Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but ...

Outcomes, utilization, and costs among thalassemia and sickle cell disease patients receiving deferoxamine therapy in the United States.

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Delea, Thomas E; Hagiwara, May; Thomas, Simu K; Baladi, Jean-Francois; Phatak, Pradyumna D; Coates, Thomas D

2008-04-01

Deferoxamine mesylate (DFO) reduces morbidity and mortality associated with transfusional iron overload. Data on the utilization and costs of care among U.S. patients receiving DFO in typical clinical practice are limited however. This was a retrospective study using a large U.S. health insurance claims database spanning 1/97-12/04 and representing 40 million members in >70 health plans. Study subjects (n = 145 total, 106 sickle cell disease [SCD], 39 thalassemia) included members with a diagnosis of thalassemia or SCD, one or more transfusions (whole blood or red blood cells), and one or more claims for DFO. Mean transfusion episodes were 12 per year. Estimated mean DFO use was 307 g/year. Central venous access devices were required by 20% of patients. Cardiac disease was observed in 16% of patients. Mean total medical costs were $59,233 per year including $10,899 for DFO and $8,722 for administration of chelation therapy. In multivariate analyses, potential complications of iron overload were associated with significantly higher medical care costs. In typical clinical practice, use of DFO in patients with thalassemia and SCD receiving transfusions is low. Administration costs represent a large proportion of the cost of chelation therapy. Potential complications of iron overload are associated with increased costs. (c) 2007 Wiley-Liss, Inc.

Cerebrovascular reserve capacity is impaired in patients with sickle cell disease

NARCIS (Netherlands)

Nur, Erfan; Kim, Yu-Sok; Truijen, Jasper; van Beers, Eduard J.; Davis, Shyrin C. A. T.; Brandjes, Dees P.; Biemond, Bart J.; van Lieshout, Johannes J.

2009-01-01

Sickle cell disease (SCD) is associated with a high incidence of ischemic stroke. SCD is characterized by hemolytic anemia, resulting in reduced nitric oxide-bioavailability, and by impaired cerebrovascular hemodynamics. Cerebrovascular CO2 responsiveness is nitric oxide dependent and has been

CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients.

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Afifi, Rasha Abdel-Raouf; Kamal, Dina; Sayed, Riham El; Ekladious, Sherif M M; Shaheen, Gehan H; Yousry, Sherif M; Hussein, Rania Elsayed

2018-06-01

To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity. A total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014. Comparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = .742). In addition, comparison of the allelic frequency did not show statistically significant difference (p = .738). Infections occurred more frequently among the heterozygous genotype (AG; 60.5%) and homozygous genotype (GG; 75%) patients than among the wild (AA) genotype (24.1%; p G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients. Copyright © 2017. Published by Elsevier Ltd.

Aberrant monocyte responses predict and characterize dengue virus infection in individuals with severe disease.

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Yong, Yean K; Tan, Hong Y; Jen, Soe Hui; Shankar, Esaki M; Natkunam, Santha K; Sathar, Jameela; Manikam, Rishya; Sekaran, Shamala D

2017-05-31

Currently, several assays can diagnose acute dengue infection. However, none of these assays can predict the severity of the disease. Biomarkers that predicts the likelihood that a dengue patient will develop a severe form of the disease could permit more efficient patient triage and allows better supportive care for the individual in need, especially during dengue outbreaks. We measured 20 plasma markers i.e. IFN-γ, IL-10, granzyme-B, CX3CL1, IP-10, RANTES, CXCL8, CXCL6, VCAM, ICAM, VEGF, HGF, sCD25, IL-18, LBP, sCD14, sCD163, MIF, MCP-1 and MIP-1β in 141 dengue patients in over 230 specimens and correlate the levels of these plasma markers with the development of dengue without warning signs (DWS-), dengue with warning signs (DWS+) and severe dengue (SD). Our results show that the elevation of plasma levels of IL-18 at both febrile and defervescence phase was significantly associated with DWS+ and SD; whilst increase of sCD14 and LBP at febrile phase were associated with severity of dengue disease. By using receiver operating characteristic (ROC) analysis, the IL-18, LBP and sCD14 were significantly predicted the development of more severe form of dengue disease (DWS+/SD) (AUC = 0.768, P dengue disease. Given that the elevation IL-18, LBP and sCD14 among patients with severe form of dengue disease, our findings suggest a pathogenic role for an aberrant inflammasome and monocyte activation in the development of severe form of dengue disease.

Thrombolytic therapy for the treatment of acute ischaemic stroke in adults with homozygous sickle cell disease.

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Majhadi, Loubna; Calvet, David; Rosso, Charlotte; Bartolucci, Pablo

2017-07-28

Stroke is a significant cause of morbidity and mortality in patients with homozygous sickle cell disease (SCD). A specific large-vessel vasculopathy is often responsible for both haemorrhagic and ischaemic strokes in patients with SCD. Although intravenous thrombolysis has been considered as a therapeutic option for acute ischaemic strokes in SCD, its use remains debated because of an increased risk of spontaneous intracranial haemorrhage reported in this disease. This risk of haemorrhage is mainly supported by the presence of a Moyamoya syndrome often associated with the specific vasculopathy in patients with homozygous SCD. We report two cases of patients with homozygous SCD treated with intravenous thrombolysis for an acute ischaemic stroke without haemorrhagic transformation. Our cases suggest that reperfusion strategy in acute ischaemic stroke in patients with homozygous SCD can be considered once associated Moyamoya syndrome has been ruled out. An international registry would be of interest as these situations are rare. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Paediatric cardiac anaesthesia in sickle cell disease: a case series

African Journals Online (AJOL)

Paediatric patients with SCD and congenital heart defects may require ... Patients with sickle cell disease (SCD) presenting for cardiac ... fluid, calculated according to body weight, was initiated. ... oxygen mixture and intravenous fentanyl (5–10 mcg/kg) and .... erythropoiesis, and in this way reduces HbS production.

Burden, genotype and phenotype profiles of adult patients with ...

African Journals Online (AJOL)

burden of SCD disease, with in excess of 300 000 new affected births annually ... child births globally.[3] In spite of the high burden of disease in SSA, SCD is often ..... supportive medication such as folic acid and patient clinic attendance.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

Science.gov (United States)

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

BK Virus Load Associated with Serum Levels of sCD30 in Renal Transplant Recipients

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Malik, Salma N.; Al-Saffer, Jinan M.; Jawad, Rana S.

2016-01-01

Background. Rejection is the main drawback facing the renal transplant operations. Complicated and overlapping factors, mainly related to the immune system, are responsible for this rejection. Elevated serum levels of sCD30 were frequently recorded as an indicator for renal allograft rejection, while BV virus is considered as one of the most serious consequences for immunosuppressive treatment of renal transplant recipients (RTRs). Aims. This study aimed to determine the association of BK virus load with serum levels of sCD30 in RTRs suffering from nephropathy. Patients and Methods. A total of 50 RTRs with nephropathy and 30 age-matched apparently healthy individuals were recruited for this study. Serum samples were obtained from each participant. Real-time PCR was used to quantify BK virus load in RTRs serum, while ELISA technique was employed to estimate serum levels of sCD30. Results. Twenty-two percent of RTRs had detectable BKV with mean viral load of 1.094E + 06 ± 2.291E + 06. RTRs showed higher mean serum level of sCD30 (20.669 ± 18.713 U/mL) than that of controls (5.517 ± 5.304 U/mL) with significant difference. BK virus load had significant positive correlation with the serum levels of sCD30 in RTRs group. Conclusion. These results suggest that serum levels of sCD30 could be used as an indicator of BK viremia, and accordingly the immunosuppressive regime should be adjusted. PMID:27051424

Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study

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Arlet Jean-Benoît

2012-08-01

Full Text Available Abstract Background Sickle cell disease (SCD leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR in SCD adult patients. Methods We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard. The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Results Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]. Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2 was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01. The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. Conclusions We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular

Lead Toxicity in the Pediatric Patient with Sickle Cell Disease: Unique Risks and Management.

Science.gov (United States)

Jung, Josephine Misun; Peddinti, Radhika

2018-01-01

Lead toxicity is the result of lead ingestion, one of the most common ingestions in the pediatric population. Nationwide and statewide efforts to recognize and curtail this epidemic have led to declining rates of toxicity. In patients with sickle cell disease (SCD), lead toxicity can be an elusive diagnosis due to overlapping symptom profiles, and inconsistent follow-up with a primary care physician can make the diagnosis even more difficult. In this article, two illustrative cases of lead toxicity in patients with SCD are described. The discussion reviews the current risk factors, screening, and inpatient management of lead toxicity, as well as describing the unique and sometimes confounding presentations of lead toxicity versus sickle cell crisis. [Pediatr Ann. 2018;47(1):e36-e40.]. Copyright 2018, SLACK Incorporated.

MRA of the intracranial circulation in asymptomatic patients with sickle cell disease

International Nuclear Information System (INIS)

Gillams, A.R.; McMahon, L.; Weinberg, G.; Carter, A.P.

1998-01-01

Background. MR angiography (MRA) provides a mechanism for non-invasively studying blood flow, thus providing a new opportunity to study the intracranial circulation in asymptomatic sickle cell disease (SCD) patients. Although conventional angiography is the gold standard for the depiction of vascular anatomy, this is too invasive for an asymptomatic population. Objective. To establish the range of appearances in asymptomatic SCD patients and to correlate brain MRI results (either sub-clinical abnormalities or normal brain parenchyma) with the MRA findings. Materials and methods. Brain MRI and MRA of the intracranial circulation was performed on 22 patients (13 male and 9 female, median age 7.5 years, range 1.3-20 years). Fourteen were homozygous SS and eight were SC. The median haematocrit at the time of MRI was 25.9 (range 13.8-33.3). Results. On MR imaging, four patients had infarcts in eight vascular territories (six anterior and two posterior). In 3/4 of anterior vascular territories with infarction, long (≥ 6 mm) segments of abnormal signal were seen at the internal carotid artery bifurcation with associated reduced distal flow. Short focal areas of abnormal signal were commonly seen where vessels branched, bifurcated or curved and were not associated with infarcts. These areas probably represent turbulence-related dephasing secondary to high velocity flow found in SCD. Conclusion. Long segments (≥ 6 mm) of abnormal signal with reduced distal flow correlated with sub-clinical infarction. (orig.)

Cellular function reinstitution of offspring red blood cells cloned from the sickle cell disease patient blood post CRISPR genome editing

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Jianguo Wen

2017-06-01

Full Text Available Abstract Background Sickle cell disease (SCD is a disorder of red blood cells (RBCs expressing abnormal hemoglobin-S (HbS due to genetic inheritance of homologous HbS gene. However, people with the sickle cell trait (SCT carry a single allele of HbS and do not usually suffer from SCD symptoms, thus providing a rationale to treat SCD. Methods To validate gene therapy potential, hematopoietic stem cells were isolated from the SCD patient blood and treated with CRISPR/Cas9 approach. To precisely dissect genome-editing effects, erythroid progenitor cells were cloned from single colonies of CRISPR-treated cells and then expanded for simultaneous gene, protein, and cellular function studies. Results Genotyping and sequencing analysis revealed that the genome-edited erythroid progenitor colonies were converted to SCT genotype from SCD genotype. HPLC protein assays confirmed reinstallation of normal hemoglobin at a similar level with HbS in the cloned genome-edited erythroid progenitor cells. For cell function evaluation, in vitro RBC differentiation of the cloned erythroid progenitor cells was induced. As expected, cell sickling assays indicated function reinstitution of the genome-edited offspring SCD RBCs, which became more resistant to sickling under hypoxia condition. Conclusions This study is an exploration of genome editing of SCD HSPCs.

Hydroxyurea therapy in adult Nigerian sickle cell disease: a monocentric survey on pattern of use, clinical effects and patient's compliance.

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Adewoyin, Ademola Samson; Oghuvwu, Omokiniovo Sunday; Awodu, Omolade Augustina

2017-03-01

The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects. A cross sectional pilot survey was carried out among 60 adult SCD subjects over 3 months. Data on clinical phenotypes, relevant haematological parameters and details of hydroxyurea therapy were obtained using a structured questionnaire through an interview process and case file review. The median age was 30 years. Thirty-four (56.7%) of the subjects are aware of hydroxyurea therapy in SCD. Twenty-four (40%) SCD patients had previously used hydroxyurea. Only 4 subjects were fully compliant. Reasons for non-compliance included poor knowledge and lack of funds. In particular, hydroxyurea reduced leucocyte count and increased mean red cell volume (MCV) in compliant subjects. Hydroxyurea use is low among Nigerian SCD subjects despite its proven efficacy/clinical prospects in the developed nations. Large scale multicenter studies and clinical trials are needed to form a basis for developing standard local treatment protocol for its use.

Pain management in children with sickle cell disease.

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Stinson, Jennifer; Naser, Basem

2003-01-01

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

Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors

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Aleem Aamer

2010-01-01

Full Text Available Renal involvement in patients with sickle cell disease (SCD is associated with signi-ficant morbidity and mortality. Proteinuria is common in patients with SCD and is a risk factor for future development of renal failure. We sought to identify risk factors, if any, associated with pro-teinuria in adult Saudi patients with SCD. We studied 67 patients with SCD followed-up at the King Khalid University Hospital, Riyadh, Saudi Arabia. All patients underwent 24-hour urine collection to measure creatinine clearance and to quantify proteinuria. In addition, blood was examined for evaluation of hematological and biochemical parameters. Clinical information was gathered from review of the patients′ charts. A urine protein level of more than 0.150 grams/24 hours was consi-dered abnormal. Urine protein was correlated with various clinical and laboratory parameters. Thirty-one males and 36 females were evaluated. The mean age of the cohort was 23.8 (± 7.2 years. Twenty-seven patients (40.3% had proteinuria of more than 0.150 grams/24 hours. The study group had a mean hemoglobin level of 8.5 (± 2.8 g/dL and mean fetal hemoglobin (HbF level of 14.4% (± 7.3%. Majority of the patients (61 had hemoglobin SS genotype and six patients had S-β0 thala-ssemia. None of the parameters evaluated correlated with proteinuria although there was a border-line association with older age and higher systolic blood pressure (P = 0.073 and 0.061 respec-tively. Hydroxyurea use for more than a year was not beneficial. In conclusion, our study suggests that proteinuria in adult Saudi patients is not associated with any clear identifiable risk factors.

Disease severity and slower psychomotor speed in adults with sickle cell disease.

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Jorgensen, Dana R; Metti, Andrea; Butters, Meryl A; Mettenburg, Joseph M; Rosano, Caterina; Novelli, Enrico M

2017-09-26

Psychomotor slowing is common in children with sickle cell disease (SCD), but little is known about its severity in adults. We conducted a cross-sectional study to quantify psychomotor speed, measured with the digit symbol substitution test (DSST), in relationship with disease severity in adults with SCD attending an outpatient clinic (n = 88, age 36.3 years). Genotype was used to group patients in "severe" (homozygous for hemoglobin S or compound heterozygous with β 0 thalassemia) or "moderate" groups (compound heterozygous for HbS, with either HbC or β + thalassemia). Analyses were repeated after exclusion of patients with a history of stroke (n = 11). Mild impairment in processing speed was detectable in both the "severe" and the "moderate" group (30% and 9%, respectively; age-adjusted P = .14). Compared with the "moderate" group, those in the "severe" group had significantly lower standardized DSST scores ( P = .004), independent of adjustment for factors that differed between the groups: hemoglobin, ferritin, hydroxyurea use, blood pressure parameters, and stroke history. Results were similar after excluding patients with stroke. Psychomotor slowing in SCD differs in relationship to genotype; this difference appears unrelated to history of stroke or severity of anemia and other risk factors examined cross-sectionally. Although less prevalent, mild cognitive impairment was also detectable in patients with a less severe genotype. Longitudinal studies of SCD should include all diseases genotypes and examine factors that would reduce the risk of slow processing speed and perhaps more general cognitive impairment in each subgroup.

A double-blind, randomized, multicenter phase 2 study of prasugrel versus placebo in adult patients with sickle cell disease

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Wun Ted

2013-02-01

Full Text Available Abstract Background Platelet activation has been implicated in the pathogenesis of sickle cell disease (SCD suggesting antiplatelet agents may be therapeutic. To evaluate the safety of prasugrel, a thienopyridine antiplatelet agent, in adult patients with SCD, we conducted a double-blind, randomized, placebo-controlled study. Methods The primary endpoint, safety, was measured by hemorrhagic events requiring medical intervention. Patients were randomized to prasugrel 5 mg daily (n = 41 or placebo (n = 21 for 30 days. Platelet function by VerifyNow® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients. Results There were no hemorrhagic events requiring medical intervention in either study arm. Mean pain rate (percentage of days with pain and intensity in the prasugrel arm were decreased compared with placebo. However, these decreases did not reach statistical significance. Platelet surface P-selectin and plasma soluble P-selectin, biomarkers of in vivo platelet activation, were significantly reduced in SCD patients receiving prasugrel compared with placebo. In sum, prasugrel was well tolerated and not associated with serious hemorrhagic events. Conclusions Despite the small size and short duration of this study, there was a decrease in platelet activation biomarkers and a trend toward decreased pain.

Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

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Hovsepyan Meri

2010-09-01

Full Text Available Abstract Background Stearoyl-CoA desaturase 1 (SCD1 is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. Inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Results Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

High soluble CD30, CD25 and IL-6 may identify patients with worse survival in CD30+ cutaneous lymphomas and early mycosis fungoides

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Kadin, Marshall E.; Pavlov, Igor; Delgado, Julio C.; Vonderheid, Eric C.

2011-01-01

Histopathology alone cannot predict outcome of patients with CD30+ primary cutaneous lymphoproliferative disorders (CD30CLPD) and early mycosis fungoides (MF). To test the hypothesis that serum cytokines/cytokine receptors provide prognostic information in these disorders, we measured soluble CD30 (sCD30), sCD25, and selected cytokines in cell cultures and sera of 116 patients with CD30CLPD and 96 patients with early MF followed up to 20 years. Significant positive correlation was found between sCD30 levels and sCD25, CD40L, IL-6, and IL-8, suggesting CD30+ neoplastic cells secrete these cytokines, but not Th2 cytokines. In vitro studies confirmed sCD30, sCD25, IL-6 and IL-8 are secreted by CD30CLPD-derived cell lines. CD30CLPD patients with above normal sCD30 and sCD25 had worse overall and disease-related survivals, but only sCD30 retained significance in Cox models that included advanced age. High sCD30 also identified patients with worse survival in early MF. Increased IL-6 and IL-8 correlated with poor disease-related survival in CD30CLPD patients, We conclude that: (1) neoplastic cells of some CD30CLPD patients do not resemble Th2 cells, (2) high serum sCD30, sCD25, IL-6, and perhaps IL-8 levels may provide prognostic information useful for patient management. PMID:22071475

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease.

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Case, Michelle; Zhang, Huishi; Mundahl, John; Datta, Yvonne; Nelson, Stephen; Gupta, Kalpna; He, Bin

2017-01-01

Sickle cell disease (SCD) is a red blood cell disorder that causes many complications including life-long pain. Treatment of pain remains challenging due to a poor understanding of the mechanisms and limitations to characterize and quantify pain. In the present study, we examined simultaneously recording functional MRI (fMRI) and electroencephalogram (EEG) to better understand neural connectivity as a consequence of chronic pain in SCD patients. We performed independent component analysis and seed-based connectivity on fMRI data. Spontaneous power and microstate analysis was performed on EEG-fMRI data. ICA analysis showed that patients lacked activity in the default mode network (DMN) and executive control network compared to controls. EEG-fMRI data revealed that the insula cortex's role in salience increases with age in patients. EEG microstate analysis showed patients had increased activity in pain processing regions. The cerebellum in patients showed a stronger connection to the periaqueductal gray matter (involved in pain inhibition), and negative connections to pain processing areas. These results suggest that patients have reduced activity of DMN and increased activity in pain processing regions during rest. The present findings suggest resting state connectivity differences between patients and controls can be used as novel biomarkers of SCD pain.

Sudden cardiac death in hemodialysis patients: an in-depth review.

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Green, Darren; Roberts, Paul R; New, David I; Kalra, Philip A

2011-06-01

Sudden cardiac death (SCD) is the leading cause of death in hemodialysis patients, accounting for death in up to one-quarter of this population. Unlike in the general population, coronary artery disease and heart failure often are not the underlying pathologic processes for SCD; accordingly, current risk stratification tools are inadequate when assessing these patients. Factors assuming greater importance in hemodialysis patients may include left ventricular hypertrophy, electrolyte shift, and vascular calcification. Knowledge regarding SCD in hemodialysis patients is insufficient, in part reflecting the lack of an agreed-on definition of SCD in this population, although epidemiologic studies suggest the most common times for SCD to occur are toward the end of the long 72-hour weekend interval between dialysis sessions and in the 12 hours immediately after hemodialysis. Accordingly, it is hypothesized that the dialysis procedure itself may have important implications for SCD. Supporting this is recognition that hemodialysis is associated with both ventricular arrhythmias and dynamic electrocardiographic changes. Importantly, echocardiography and electrocardiography may show changes that are modifiable by alterations to dialysis prescription. The most effective preventative strategy in the general population, implanted cardioverter-defibrillator devices, are less effective in the presence of chronic kidney disease and have not been studied adequately in dialysis patients. Last, many dialysis patients experience SCD despite not fulfilling current criteria for implantation, making appropriate allocation of defibrillators uncertain. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Patients with sickle cell disease are frequently excluded from the benefits of transcranial doppler screening for the risk of stroke despite extensive and compelling evidence

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Daniela Laranja Gomes Rodrigues

Full Text Available ABSTRACT Transcranial doppler (TCD is a strategic component of primary stroke prevention in children with sickle cell disease (SCD. This study was conducted to examine the TCD characteristics of children with SCD in nine different medical centers in Brazil. Methods: Transcranial doppler was performed in accordance with the Stroke Prevention Trial in Sickle Cell Anemia Protocol. Results: Of the 396 patients, 69.5% had homozygous SS hemoglobin. The TCD result was abnormal in 4.8%, conditional in 12.6%, inadequate in 4.3% and abnormally low in 1% of patients. The highest mean flow velocities were 121±23.83cm/s and 124±27.21cm/s in the left and right middle cerebral artery respectively. A total of 28.8% patients (mean age 9.19±5.92 years were evaluated with TCD for the first time. Conclusions: The SCD patients were evaluated with TCD at an older age, representing an important missed opportunity for stroke prevention. Since TCD screening in patients with SCD is important to detect those at high risk for stroke, it is recommended that this screening should be made more readily available.

Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.

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Casas, Jessica; Friedman, David F; Jackson, Tannoa; Vege, Sunitha; Westhoff, Connie M; Chou, Stella T

2015-06-01

Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported. This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles. Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fy(b) expression. DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution. © 2015 AABB.

Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus.

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Otterdal, Kari; Janardhanan, Jeshina; Astrup, Elisabeth; Ueland, Thor; Prakash, John A J; Lekva, Tove; Abraham, O C; Thomas, Kurien; Damås, Jan Kristian; Mathews, Prasad; Mathai, Dilip; Aukrust, Pål; Varghese, George M

2014-11-01

Scrub typhus is endemic in the Asia-Pacific region. Mortality is high even with treatment, and further knowledge of the immune response during this infection is needed. This study was aimed at comparing plasma levels of monocyte/macrophage and endothelial related inflammatory markers in patients and controls in South India and to explore a possible correlation to disease severity and clinical outcome. Plasma levels of ALCAM, VCAM-1, sCD163, sCD14, YKL-40 and MIF were measured in scrub typhus patients (n = 129), healthy controls (n = 31) and in infectious disease controls (n = 31), both in the acute phase and after recovery, by enzyme immunoassays. Patients had markedly elevated levels of all mediators in the acute phase, differing from both healthy and infectious disease controls. During follow-up levels of ALCAM, VCAM-1, sCD14 and YKL-40 remained elevated compared to levels in healthy controls. High plasma ALCAM, VCAM-1, sCD163, sCD14, and MIF, and in particular YKL-40 were all associated with disease severity and ALCAM, sCD163, MIF and especially YKL-40, were associated with mortality. Our findings show that scrub typhus is characterized by elevated levels of monocyte/macrophage and endothelial related markers. These inflammatory markers, and in particular YKL-40, may contribute to disease severity and clinical outcome. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response.

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Tue Wenzel Kragstrup

Full Text Available In rheumatoid arthritis (RA immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18 in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis.The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1 plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort, 2 plasma from chronic RA patients, 3 serum from SKG and CIA mice following arthritis induction, and 4 supernatants from synovial fluid mononuclear cells (SFMCs and peripheral blood mononuclear cells (PBMCs from 6 RA patients cultured with TNFα or adalimumab.Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab.The plasma sCD18 levels were altered in patients with RA, in mice

Single-case synthesis tools I: Comparing tools to evaluate SCD quality and rigor.

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Zimmerman, Kathleen N; Ledford, Jennifer R; Severini, Katherine E; Pustejovsky, James E; Barton, Erin E; Lloyd, Blair P

2018-03-03

Tools for evaluating the quality and rigor of single case research designs (SCD) are often used when conducting SCD syntheses. Preferred components include evaluations of design features related to the internal validity of SCD to obtain quality and/or rigor ratings. Three tools for evaluating the quality and rigor of SCD (Council for Exceptional Children, What Works Clearinghouse, and Single-Case Analysis and Design Framework) were compared to determine if conclusions regarding the effectiveness of antecedent sensory-based interventions for young children changed based on choice of quality evaluation tool. Evaluation of SCD quality differed across tools, suggesting selection of quality evaluation tools impacts evaluation findings. Suggestions for selecting an appropriate quality and rigor assessment tool are provided and across-tool conclusions are drawn regarding the quality and rigor of studies. Finally, authors provide guidance for using quality evaluations in conjunction with outcome analyses when conducting syntheses of interventions evaluated in the context of SCD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Macrophage activation marker sCD163 correlates with accelerated lipolysis following LPS exposure: a human-randomised clinical trial

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Nikolaj Rittig

2018-01-01

Full Text Available Background: Macrophage activation determined by levels of soluble sCD163 is associated with obesity, insulin resistance, diabetes mellitus type 2 (DM2 and non-alcoholic fatty liver disease (NAFLD. This suggests that macrophage activation is involved in the pathogenesis of conditions is characterised by adaptions in the lipid metabolism. Since sCD163 is shed to serum by inflammatory signals including lipopolysaccharides (LPS, endotoxin, we investigated sCD163 and correlations with lipid metabolism following LPS exposure. Methods: Eight healthy male subjects were investigated on two separate occasions: (i following an LPS exposure and (ii following saline exposure. Each study day consisted of a four-hour non-insulin-stimulated period followed by a two-hour hyperinsulinemic euglycemic clamp period. A 3H-palmitate tracer was used to calculate the rate of appearance (Rapalmitate. Blood samples were consecutively obtained throughout each study day. Abdominal subcutaneous adipose tissue was obtained for western blotting. Results: We observed a significant two-fold increase in plasma sCD163 levels following LPS exposure (P < 0.001, and sCD163 concentrations correlated positively with the plasma concentration of free fatty acids, Rapalmitate, lipid oxidation rates and phosphorylation of the hormone-sensitive lipase at serine 660 in adipose tissue (P < 0.05, all. Furthermore, sCD163 concentrations correlated positively with plasma concentrations of cortisol, glucagon, tumour necrosis factor (TNF-α, interleukin (IL-6 and IL-10 (P < 0.05, all. Conclusion: We observed a strong correlation between sCD163 and stimulation of lipolysis and fat oxidation following LPS exposure. These findings support preexisting theory that inflammation and macrophage activation play a significant role in lipid metabolic adaptions under conditions such as obesity, DM2 and NAFLD.

Improvement of field matching in segmented-field electron conformal therapy using a variable-SCD applicator

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Richert, John D [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Hogstrom, Kenneth R [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Fields, Robert S [Mary Bird Perkins Cancer Center, 4950 Essen Lane, Baton Rouge, LA 70809-3482 (United States); II, Kenneth L Matthews [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States); Boyd, Robert A [Department of Physics and Astronomy, Louisiana State University, 202 Nicholson Hall, Baton Rouge, LA 70803-4001 (United States)

2007-05-07

The purpose of the present study is to demonstrate that the use of an electron applicator with energy-dependent source-to-collimator distances (SCDs) will significantly improve the dose homogeneity for abutted electron fields in segmented-field electron conformal therapy (ECT). Multiple Coulomb scattering theory was used to calculate and study the P{sub 80-20} penumbra width of off-axis dose profiles as a function of air gap and depth. Collimating insert locations with air gaps (collimator-to-isocenter distance) of 5.0, 7.5, 11.5, 17.5 and 19.5 cm were selected to provide equal P{sub 80-20} at a depth of 1.5 cm in water for energies of 6, 9, 12, 16 and 20 MeV, respectively, for a Varian 2100EX radiation therapy accelerator. A 15 x 15 cm{sup 2} applicator was modified accordingly, and collimating inserts used in the variable-SCD applicator for segmented-field ECT were constructed with diverging edges using a computer-controlled hot-wire cutter, which resulted in 0.27 mm accuracy in the abutted edges. The resulting electron beams were commissioned for the pencil-beam algorithm (PBA) on the Pinnacle{sup 3} treatment planning system. Four hypothetical planning target volumes (PTVs) and one patient were planned for segmented-field ECT using the new variable-SCD applicator, and the resulting dose distributions were compared with those calculated for the identical plans using the conventional 95 cm SCD applicator. Also, a method for quality assurance of segmented-field ECT dose plans using the variable-SCD applicator was evaluated by irradiating a polystyrene phantom using the treatment plans for the hypothetical PTVs. Treatment plans for all four of the hypothetical PTVs using the variable-SCD applicator showed significantly improved dose homogeneity in the abutment regions of the segmented-field ECT plans. This resulted in the dose spread (maximum dose-minimum dose), {sigma}, and D{sub 90-10} in the PTV being reduced by an average of 32%, 29% and 32%, respectively

Cellular, pharmacological, and biophysical evaluation of explanted lungs from a patient with sickle cell disease and severe pulmonary arterial hypertension.

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Rogers, Natasha M; Yao, Mingyi; Sembrat, John; George, M Patricia; Knupp, Heather; Ross, Mark; Sharifi-Sanjani, Maryam; Milosevic, Jadranka; St Croix, Claudette; Rajkumar, Revathi; Frid, Maria G; Hunter, Kendall S; Mazzaro, Luciano; Novelli, Enrico M; Stenmark, Kurt R; Gladwin, Mark T; Ahmad, Ferhaan; Champion, Hunter C; Isenberg, Jeffrey S

2013-12-01

Pulmonary hypertension is recognized as a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). We now report benchtop phenotyping from the explanted lungs of the first successful lung transplant in SCD. Pulmonary artery smooth muscle cells (PASMCs) cultured from the explanted lungs were analyzed for proliferate capacity, superoxide (O2 (•-)) production, and changes in key pulmonary arterial hypertension (PAH)-associated molecules and compared with non-PAH PASMCs. Upregulation of several pathologic processes persisted in culture in SCD lung PASMCs in spite of cell passage. SCD lung PASMCs showed growth factor- and serum-independent proliferation, upregulation of matrix genes, and increased O2 (•-) production compared with control cells. Histologic analysis of SCD-associated PAH arteries demonstrated increased and ectopically located extracellular matrix deposition and degradation of elastin fibers. Biomechanical analysis of these vessels confirmed increased arterial stiffening and loss of elasticity. Functional analysis of distal fifth-order pulmonary arteries from these lungs demonstrated increased vasoconstriction to an α1-adrenergic receptor agonist and concurrent loss of both endothelial-dependent and endothelial-independent vasodilation compared with normal pulmonary arteries. This is the first study to evaluate the molecular, cellular, functional, and mechanical changes in end-stage SCD-associated PAH.

Attention Deficit Hyperactivity Disorder in Children With Sickle Cell Disease Referred for an Evaluation.

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Acquazzino, Melissa A; Miller, Meghan; Myrvik, Matthew; Newby, Robert; Scott, John Paul

2017-07-01

Neuropsychological deficits, including difficulties with attention, are well described in children with sickle cell disease (SCD). Very little is known about attention deficit hyperactivity disorder (ADHD) in children with SCD. The objective of this study was to determine the proportion of ADHD in children with SCD referred for neuropsychological evaluation. This prospective, cross-sectional study included patients (age, 4 to 18 y) with SCD and completion of a neuropsychological evaluation between December 2013 and March 2016. Patients were referred for neuropsychological evaluation because of concern regarding school performance, development, and/or behavior. The diagnosis of ADHD was made by a neuropsychologist on the basis of the diagnostic criteria in the Diagnostic Statistical Manual-Fourth or Fifth Editions. ADHD medication usage rate was obtained by medical record review. Of the 89 patients with SCD referred for neuropsychological evaluation, 25% (95% confidence interval, 16%-35%) met diagnostic criteria for ADHD. Only 21% of the patients with SCD and ADHD were prescribed an ADHD medication. Our study supports routine ADHD screening in children with SCD who have poor school performance or behavioral concerns. Despite the benefits of pharmacologic treatment, the majority of patients with SCD and ADHD did not receive a medication for management of their ADHD.

Plasma soluble cluster of differentiation 147 levels are increased in breast cancer patients and associated with lymph node metastasis and chemoresistance.

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Kuang, Y H; Liu, Y J; Tang, L L; Wang, S M; Yan, G J; Liao, L Q

2018-05-25

Cluster of differentiation 147 (CD147) contributes to breast cancer invasion, metastasis, and multidrug resistance. Recent studies have shown that peripheral soluble CD147 (sCD147) is increased in hepatocellular tumour and multiple myeloma patients and correlated with disease severity. The primary aim of our study was to assess the level, as well as the biological and clinical significance of sCD147 in breast cancer. We tested plasma sCD147 levels in 308 breast cancer patients by enzyme-linked immunosorbent assay between February 2014 and February 2017. A subset of 165 cases of benign breast diseases was included as a control group at the same period. We analysed the clinical significance of plasma sCD147 with relevance to clinicopathological factors of breast cancer patients. Plasma sCD147 levels were significantly higher in patients with primary breast cancer than those with benign breast diseases (P=0.001), in patients with locally advanced breast cancer (T3-T4 tumour) than those in early breast cancer (T1-T2 tumour; P=0.001), in patients with lymph node metastasis than in those without (P<0.001), and in patients with high recurrence risk than those with medium recurrence risk (P<0.001). Plasma sCD147 levels were also significantly higher in the chemotherapy-resistant group than in the chemotherapy-sensitive group (P=0.040). Plasma sCD147 was an independent predictor for lymph node metastasis in breast cancer patients (P=0.001). This is the first study to demonstrate that plasma sCD147 levels are elevated in breast cancer patients. Soluble CD147 is also associated with tumour size, lymph node metastasis, high recurrent risk, and chemoresistance. Our findings support that plasma sCD147 is an independent predictive factor for lymph node metastasis.

Predicting renal graft failure by sCD30 levels and de novo HLA antibodies at 1year post-transplantation.

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Wang, Dong; Wu, Guojun; Chen, Jinhua; Yu, Ziqiang; Wu, Weizhen; Yang, Shunliang; Tan, Jianming

2012-06-01

HLA antibodies and sCD30 levels were detected in the serum sampled from 620 renal graft recipients at 1 year post-transplantation, which were followed up for 5 years. Six-year graft and patient survivals were 81.6% and 91.0%. HLA antibodies were detected in 45 recipients (7.3%), of whom there were 14 cases with class I antibodies, 26 cases with class II, and 5 cases with both class I and II. Much more graft loss was record in recipients with HLA antibodies than those without antibodies (60% vs. 15.1%, psCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, psCD30 levels, recipients with low sCD30 levels (sCD30 on graft survival was not only independent but also additive. Therefore, post-transplantation monitoring of HLA antibodies and sCD30 levels is necessary and recipients with elevated sCD30 level and/or de novo HLA antibody should be paid more attention in order to achieve better graft survival. Copyright © 2012 Elsevier B.V. All rights reserved.

Caregiver Perspectives of Stigma Associated With Sickle Cell Disease in Adolescents.

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Wesley, Kimberly M; Zhao, Mimi; Carroll, Yvonne; Porter, Jerlym S

2016-01-01

Patients and families affected by various medical conditions report experiencing health-related stigma, which contributes to detrimental physical, psychological, and social outcomes. Sickle cell disease (SCD) is a genetic disorder that affects 89,000 individuals in the United States and is often associated with negative stereotypes and incorrect assumptions. The present study explored the perception of stigma as reported by caregivers of adolescents with SCD. Focus groups were conducted with 20 caregivers of patients with SCD. Focus groups were audio recorded and transcribed. The data were coded independently by two authors, and then reviewed conjointly until consensus was reached. Caregivers reported the perception of stigma in academic, medical, community, and family settings. They also reported internalized stigma including negative feelings toward having a child with SCD, feeling upset with others, and seeing negative emotions in their child due to SCD. Caregivers reported a general lack of knowledge about SCD across settings. These results demonstrated that stigma may affect individuals with SCD across multiple settings. These results also highlighted areas for intervention, with a focus on increasing communication and education toward medical providers, schools, and communities. Interventions can utilize technology, social media, and advertisement campaigns. Additionally, support groups for patients with SCD may help decrease stigma and validate patients' experiences. Copyright © 2016 Elsevier Inc. All rights reserved.

Original Research: Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin SC disease.

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Summarell, Carly C Ginter; Sheehan, Vivien A

2016-04-01

Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease. © 2016 by the Society for Experimental Biology and Medicine.

The clinical impact of MTHFR polymorphism on the vascular complications of sickle cell disease

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F. Moreira Neto

2006-10-01

Full Text Available Sickle cell disease (SCD is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden, the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women, 29 with SS (sickle cell anemia; 28 years, range: 13-52 years and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8% and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8% and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease, a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.

Double disadvantage: a case control study on health-related quality of life in children with sickle cell disease

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Heijboer Harriët

2010-10-01

Full Text Available Abstract Background Low health-related quality of life (HRQoL of children with sickle cell disease (SCD may be associated with consequences of the disease, or with the low socio-economic status (SES of this patient population. The aim of this study was to investigate the HRQoL of children with SCD, controlling for SES by comparing them to healthy siblings (matched for age and gender, and to a Dutch norm population. Methods The HRQoL of 40 children with homozygous SCD and 36 healthy siblings was evaluated by the KIDSCREEN-52. This self-report questionnaire assesses ten domains of HRQoL. Differences between children with SCD and healthy siblings were analyzed using linear mixed models. One-sample t-tests were used to analyze differences with the Dutch norm population. Furthermore, the proportion of children with SCD with impaired HRQoL was evaluated. Results In general, the HRQoL of children with SCD appeared comparable to the HRQoL of healthy siblings, while children with SCD had worse HRQoL than the Dutch norm population on five domains (Physical Well-being, Moods & Emotions, Autonomy, Parent Relation, and Financial Resources. Healthy siblings had worse HRQoL than the Dutch norm population on three domains (Moods & Emotions, Parent Relation, and Financial Resources. More than one in three children with SCD and healthy siblings had impaired HRQoL on several domains. Conclusion These findings imply that reduced HRQoL in children with SCD is mainly related to the low SES of this patient population, with the exception of disease specific effects on the physical and autonomy domain. We conclude that children with SCD are especially vulnerable compared to other patient populations, and have special health care needs.

Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

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Santos, Allan [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil); Servico de Medicina Nuclear, Hospital das Clinicas da UNICAMP, Campina (Brazil); Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia [Centro Infantil Domingos A. Boldrini, Campinas (Brazil); Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E. [Division of Nuclear Medicine, Department of Radiology, Campinas State University (UNICAMP), Campinas (Brazil)

2002-04-01

Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with S{beta}{sup 0} haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one S{beta}{sup 0} patient and impaired splenic function in five SS patients and six S{beta}{sup 0} patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

Scintigraphic follow-up of the effects of therapy with hydroxyurea on splenic function in patients with sickle cell disease

International Nuclear Information System (INIS)

Santos, Allan; Pinheiro, Vitoria; Anjos, Ana Claudia; Brandalise, Silvia; Fahel, Fernanda; Lima, Mariana; Etchebehere, Elba; Ramos, Celso; Camargo, Edwaldo E.

2002-01-01

Patients with sickle cell disease (SCD) may develop functional asplenia as a chronic complication, secondary to repeated episodes of polymerisation of haemoglobin S. It is known that increased plasma concentrations of fetal haemoglobin (HbF) reduce the polymerisation of haemoglobin S. Hydroxyurea is a chemotherapeutic agent capable of increasing HbF levels in the red blood cells and its use has recently been proposed in the treatment of SCD. The objective of this study was to evaluate the effects of long-term therapy with hydroxyurea on recovery of splenic function. Twenty-one patients (aged 3-22 years; 14 with SS haemoglobinopathy, 7 with Sβ 0 haemoglobinopathy) were studied with liver/spleen scintigraphy before and after 6 and 12 months of treatment. All studies were submitted to visual inspection and semi-quantitative analyses using spleen/liver ratios. Imaging prior to treatment demonstrated functional asplenia in nine SS patients and one Sβ 0 patient and impaired splenic function in five SS patients and six Sβ 0 patients. After treatment, splenic function improved in ten patients, remained unchanged in eight and worsened in three. Using liver/spleen imaging, it was possible to demonstrate that hydroxyurea is capable of improving splenic function in some SCD patients. Improvement is not always possible and frequently does not lead to a normal splenic function even after 1 year of treatment. (orig.)

Patient-reported outcomes of deferasirox (Exjade, ICL670) versus deferoxamine in sickle cell disease patients with transfusional hemosiderosis. Substudy of a randomized open-label phase II trial.

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Vichinsky, Elliott; Pakbaz, Zahra; Onyekwere, Onyinye; Porter, John; Swerdlow, Paul; Coates, Thomas; Lane, Peter; Files, Beatrice; Mueller, Brigitta U; Coïc, Lena; Forni, Gian Luca; Fischer, Roland; Marks, Peter; Rofail, Diana; Abetz, Linda; Baladi, Jean-Francois

2008-01-01

There is increasing evidence demonstrating the value of transfusions in sickle cell disease (SCD). However, resultant iron overload can be life threatening if untreated. Chelation therapy with deferoxamine requires parenteral infusions that can negatively impact quality of life and adherence to treatment. As part of a phase II trial, SCD patient-reported outcomes were evaluated. One hundred and ninety-five patients were randomized (2:1) to receive oral deferasirox (5-30 mg/kg/day) or deferoxamine (20-50 mg/kg, 5 days per week); 121 had previously received deferoxamine. At each time point, significantly more patients who had previously received deferoxamine were 'satisfied/very satisfied' with deferasirox, or found treatment to be 'convenient/very convenient' compared with deferoxamine (p < 0.001). In these patients, fewer hours were lost from daily activities with deferasirox than deferoxamine treatment. Most patients (77%) preferred deferasirox, and more were willing to continue taking deferasirox than deferoxamine at end-of-study (84 vs. 11%, respectively). Patients with SCD are therefore more satisfied with deferasirox, which has a lower impact on daily activities than deferoxamine. Given the high levels of satisfaction, it is likely that quality of life will be improved. These results also suggest that treatment adherence with deferasirox may be better than with deferoxamine, which should lead to improved long-term outcomes. 2008 S. Karger AG, Basel.

Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients

NARCIS (Netherlands)

van der Dijs, FPL; Schnog, JJB; Brouwer, DAJ; Velvis, HJR; van den Berg, GA; Bakker, AJ; Duits, AJ; Muskiet, FD

1998-01-01

We investigated whether pediatric patients with sickle cell disease (SCD) (9 +/- 4 years; 27 homozygous SCD [HbSS]; 19 sickle-C disease [HbSC]) have different folate status compared with age-, sex-, and race-matched normal hemoglobin (HbAA) controls (n = 20), and whether their folate status can be

Practice patterns and clinical significance of use of capsule endoscopy in suspected and established Crohn's disease

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Yonghyun Kim

2017-10-01

Full Text Available Background/Aims: Although the role of capsule endoscopy (CE in Crohn's disease (CD has expanded, CE is not used routinely for diagnosing and evaluating CD in Korea. We aimed to investigate current patterns of practice and evaluate the clinical significance of the use of CE in CD in Korean patients.Methods: Among 651 CE procedures performed for various indications, we retrospectively analyzed the medical records of patients who underwent CE in 57 cases of suspected CD (sCD and 14 cases of established CD (eCD.Results: In the sCD group, CE was most commonly used for the initial diagnosis of CD (54.4%. Capsule retention was found in only 1 patient in the eCD group (1/71, 1.4%. In the sCD group, 28.1% of patients were diagnosed with CD on the basis of CE findings; other diseases diagnosed included tuberculous enteritis (7.0%, non-steroidal anti-inflammatory drug-induced enteropathy (5.3%, and other enteritis (17.5%. Only 11.5% of patients with eCD (14/122 underwent CE. The indication for CE in the 14 patients with eCD was to assess disease extent and activity. The overall diagnostic yield of CE was 59.7%. Therapeutic strategies were changed in 70.2% of patients in the sCD group and 50% of those in the eCD group based on CE findings.Conclusions: In clinical practice, CE was most commonly indicated for the initial diagnosis of CD and was not generally performed in patients with eCD. CE appears to be an effective diagnostic modality for evaluating sCD and is useful for determining therapeutic strategies for patients with sCD and those with eCD.

Controlling sickle cell disease in Ghana - ethics and options

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Kyerewaa Edwin, Ama; Edwin, Frank; Etwire, Victor

2011-01-01

Sickle Cell Disease (SCD) is a significant public health burden in Ghana. Recent studies indicate that 2% of Ghanaian newborns are affected by SCD; one in three Ghanaians has the hemoglobin S and/or C gene. As a means of controlling the disease, some authorities have recommended prenatal diagnosis (PND) and selective abortion. In the current era, SCD has a good prognosis and fairly reasonable quality of life. Advances in bone marrow transplantation have shown the disease is curable in selected patients. PND and selective abortion therefore raises a myriad of ethical dilemmas which are considered in this review. In the light of the demonstration of improved prognosis in recent times, PND and selective abortion appears to be applying capital punishment to the unborn child for “crimes” only the parents can be responsible for. In this review, we recommend control of SCD on three levels – preconception genetic testing and strategic reproductive choices, PND and education for carrier parents, and holistic management of persons with SCD. We emphasize the critical importance of self-management, especially self-awareness, in assuring a good quality of life for persons with SCD. We believe such an approach is cost-effective, and consistent with sound ethical principles and good conscience. PMID:22187596

Regional cerebral blood flow in patients with sickle cell disease: study with single photon emission computed tomography

International Nuclear Information System (INIS)

Al-Kandari, F.A.; Owunwanne, A.; Syed, G.M.; Elgazzar, A.H.; Rizui, A.M.; Al-Ajmi, J.A.; Mohammed, A.M.; Ar Marouf, R.; Shiekh, M.

2007-01-01

Neurological complications have been reported in patients with sickle-cell disease (SCD) using positron emission tomography (PET), magnetic resonance imaging (MRI), and computed tomography (CT), but not with single photon emission computed tomography (SPECT). The objective of this study was to investigate brain perfusion in the patients with SCD using SPECT after technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO), was administered and compare the findings with those of demography, physical examination, MRI and hematological profile. The study involved 21 patients (12 males, 9 females, age at study 8-45 years) who were known to be having SCD for a duration of at least 5 years. The patients were not in acute crisis and had normal neurological assessments with no known history of stroke or transient ischemic episode or previous abnormal CT or MRI brain scan, and were right-handed. The brain SPECT was performed after intravenous injection of 740 MBq (20 mCi) 99m Tc-HMPAO in adults or an appropriate dose in pediatric patients. The scans were visually interpreted by two nuclear medicine physicians and a decision was reached by consensus. An MRI done 3 months later was interpreted by a radiologist. The demographic data and hematological profile were obtained from the medical records of the patients. Of the 21 patients, 7 (age 11-22 years) had brain perfusion deficit mostly in the frontal lobe either alone or in combination with temporal and/or parietal lobe. The MRI was abnormal in 2 patients. The brain perfusion deficit was not associated with the demographic data of the patients or hematological profiles. The findings show that SPECT was useful in detecting brain perfusion deficit in SCD patients, and such an early detection may be clinically useful in the subsequent follow-up of such patients, since it is known that cerebral perfusion deficit can lead to silent infarct and/or overt stroke, and affect cognitive skills. (author)

Sporadic Creutzfeldt-Jakob disease in a native Puerto Rican patient.

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Del Pilar-Morales, Esteban A; Cali, Ignazio; Chapas, Javier; Bertrán-Pasarell, Jorge; Puoti, Gianfranco; Gambetti, Pierluigi; Nobo, Ulises

2015-03-01

The diagnosis of Creutzfeldt-Jakob disease (CJD) is often a challenge for most physicians given its extremely low incidence and different clinico-pathological presentations. We report the case of a 56-year old patient native to Puerto Rico suspected of sporadic Creutzfeldt-Jakob disease (sCD). The symptoms at onset were notorious for bilateral cortical blindness followed by rapidly progressive cognitive decline, visual deficit, increased levels of CSF 14-3-3 and tau along with positive brain MRI and EEG, are highly indicative of CJD. The definite diagnosis was confirmed by the National Prion Disease Pathology Surveillance Center (NPDPSC), in Cleveland, Ohio, USA. Lack of genetic mutations in the prion protein (PrP) gene, widespread histopathological changes and the accumulation of scrapie PrP (PrPSc) in the brain confirmed the diagnosis of sCJD. The patient, admitted to our institution in 2011, represents the first detailed report of sCJD in a native Puerto Rican patient living in Puerto Rico.

Changes in fat mass correlate with changes in soluble sCD163, a marker of mature macrophages, in patients with CKD

DEFF Research Database (Denmark)

Axelsson, Jonas; Møller, Holger Jon; Witasp, Anna

2006-01-01

healthy controls (mean GFR, 89 +/- 3 mL/min [1.48 +/- 0.05 mL/s]; mean age, 63 +/-2 years; 69% men) were characterized post hoc with a follow-up of up to 5 years (mean, 47 +/- 1 months). sCD163 levels, body composition (dual-energy x-ray absorptiometry), clinical parameters, and levels of circulating...... of inflammation and endothelial adhesion molecules. After 1 year, patients who increased body fat mass (average, 11% +/- 5% versus -5% +/- 5%; P

Myocardial SPECT in children with sickle cell disease

International Nuclear Information System (INIS)

Maunoury, C.; Hallaj, I.; Barritault, L.; Acar, P.; Montalembert, M. de

2002-01-01

Aim: While cerebral and bones strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Conventional techniques such as exercise testing and echocardiography have a low sensitivity and specificity to detect myocardial ischemia in patients with SCD. The aim of this prospective study was to assess myocardial perfusion with 201 Tl SPECT in children with SCD. Materials and Methods: Twenty-two patients, aged 12 ± 4 years, were included. Myocardial perfusion was assessed by 201 Tl SPECT after stress and 3 hours later after reinjection on a single head gammacamera equipped with a LEAP collimator (64x64 matrix size format, 30 projections over 180 0 , 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Results: Myocardial perfusion was impaired in 13/22 patients: 8 had reversible defects and 5 had fixed defects. The left ventricular cavity was dilated in 13/22 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. Conclusion: Myocardial perfusion is frequently impaired in children with SCD. Treatment with hydroxyurea should be considered in SCD patients with perfusion defects

Hematological profile of sickle cell disease from South Gujarat, India

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Sanjeev Shyam Rao

2012-05-01

Full Text Available The aim of this study was to determine hematological profile of sickle cell disease (SCD from Surat, South Gujarat, India. This prospective cross-sectional study was conducted in the Department of Pediatrics and Sickle Cell Anemia Laboratory, Faculty of Pathology, Government Medical College, Surat, India, between July 2009 and December 2010. Patients included in this study were in their steady state for a long period of time without any symptoms related to SCD or other diseases which could affect the hematological parameters. Venous blood of all patients was collected in ethylenediaminetetraacetic acid and hematological indices were measured. Thirty-three subjects homozygous in all were studied for their hematological parameters for sickle cell anemia. Moderate to severe anemia, low mean cell volume and high foetal hemoglobin dominate the hematological profile of SCD children.

Exercise tolerance, lung function abnormalities, anemia, and cardiothoracic ratio in sickle cell patients

NARCIS (Netherlands)

van Beers, Eduard J.; van der Plas, Mart N.; Nur, Erfan; Bogaard, Harm-Jan; van Steenwijk, Reindert P.; Biemond, Bart J.; Bresser, Paul

2014-01-01

Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty-four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age

Presence of pain on three or more days of the week is associated with worse patient reported outcomes in adults with sickle cell disease

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Bakshi N

2018-02-01

Full Text Available Nitya Bakshi,1,2 Diana Ross,1 Lakshmanan Krishnamurti1,2 1Division of Pediatric Hematology-Oncology-BMT, Department of Pediatrics, Emory University, Atlanta, GA, USA; 2Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA Abstract: While acute episodic pain is the hallmark of sickle cell disease (SCD, transition to chronic pain is a major cause of morbidity and impaired quality of life. One of the core diagnostic criteria used by Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy (AAPT to define chronic SCD pain is the presence of pain on a “majority of days” in the past 6 months in one or more locations. The frequency characteristic of “majority of days” is adapted from the criteria of 15 days or more per month, used to define chronic migraine, but there are inadequate data to support this cutoff in SCD. Using an existing dataset of adults with SCD who completed patient-reported outcomes of pain interference, physical functioning, anxiety, depression, and fatigue using the National Institutes of Health (NIH patient-reported outcomes measures information system (PROMIS short-form instruments, we examined the association of the presence of pain on 3 or more days per week with patient-reported outcomes of functioning. In unadjusted analyses, presence of pain on 3 or more days a week was associated with higher median PROMIS scores of pain interference, anxiety, and depression. Median PROMIS scores of fatigue and physical function were worse in women compared with men in unadjusted analyses. We did not find any difference in median PROMIS pain scores between adults aged ≤35 years compared with those aged ≥35 years. In linear regression models, after adjustment for age and sex, the presence of pain on 3 or more days a week was found to be associated with worse pain interference and anxiety. These data support

SCD1 Expression is dispensable for hepatocarcinogenesis induced by AKT and Ras oncogenes in mice.

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Lei Li

Full Text Available Increased de novo lipogenesis is one of the major metabolic events in cancer. In human hepatocellular carcinoma (HCC, de novo lipogenesis has been found to be increased and associated with the activation of AKT/mTOR signaling. In mice, overexpression of an activated form of AKT results in increased lipogenesis and hepatic steatosis, ultimately leading to liver tumor development. Hepatocarcinogenesis is dramatically accelerated when AKT is co-expressed with an oncogenic form of N-Ras. SCD1, the major isoform of stearoyl-CoA desaturases, catalyzing the conversion of saturated fatty acids (SFA into monounsaturated fatty acids (MUFA, is a key enzyme involved in de novo lipogenesis. While many studies demonstrated the requirement of SCD1 for tumor cell growth in vitro, whether SCD1 is necessary for tumor development in vivo has not been previously investigated. Here, we show that genetic ablation of SCD1 neither inhibits lipogenesis and hepatic steatosis in AKT-overexpressing mice nor affects liver tumor development in mice co-expressing AKT and Ras oncogenes. Molecular analysis showed that SCD2 was strongly upregulated in liver tumors from AKT/Ras injected SCD1(-/- mice. Noticeably, concomitant silencing of SCD1 and SCD2 genes was highly detrimental for the growth of AKT/Ras cells in vitro. Altogether, our study provides the evidence, for the first time, that SCD1 expression is dispensable for AKT/mTOR-dependent hepatic steatosis and AKT/Ras-induced hepatocarcinogenesis in mice. Complete inhibition of stearoyl-CoA desaturase activity may be required to efficiently suppress liver tumor development.

Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

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Wallen, Gwenyth R; Middleton, Kimberly R; Ames, Nancy; Brooks, Alyssa T; Handel, Daniel

2014-01-01

Sickle cell disease (SCD) is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality), anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION ClinicalTrials.gov: NCT00393250 PMID:25520557

Randomized Trial of Hypnosis as a Pain and Symptom Management Strategy in Adults with Sickle Cell Disease

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Gwenyth R. Wallen

2014-01-01

Full Text Available Sickle cell disease (SCD is the most common genetic disease in African-Americans, characterized by recurrent painful vaso-occlusive crises. Medical therapies for controlling or preventing crises are limited because of efficacy and/or toxicity. This is a randomized, controlled, single-crossover protocol of hypnosis for managing pain in SCD patients. Participants receive hypnosis from a trained hypnosis therapist followed by six weeks of self-hypnosis using digital media. Those in the control arm receive SCD education followed by a six-week waiting period before crossing over to the hypnosis arm of the study. Outcome measures include assessments of pain (frequency, intensity and quality, anxiety, coping strategies, sleep, depression, and health care utilization. To date, there are no published randomized, controlled trials evaluating the efficacy of hypnosis on SCD pain modulation in adults. Self-hypnosis for pain management may be helpful in modulating chronic pain, improving sleep quality, and decreasing use of narcotics in patients with SCD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00393250

Symptomatic radiation-induced cardiac disease in long-term survivors of esophageal cancer

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Iwahashi, Noriaki; Kosuge, Masami; Kimura, Kazuo [Division of Cardiology, Yokohama City University Medical Center, Yokohama (Japan); Sakamaki, Kentaro [Department of Biostatistics, Yokohama City University Medical Center, Yokohama (Japan); Kunisaki, Chikara [Department of Surgery, Gastroenterological Center, Yokohama City University Medical Center, Yokohama (Japan); Ogino, Ichiro; Watanabe, Shigenobu

2016-06-15

To evaluate clinical and dosimetric factors retrospectively affecting the risk of symptomatic cardiac disease (SCD) in esophageal cancer patients treated with radiotherapy. A total of 343 patients with newly diagnosed esophageal cancer were managed with concurrent chemoradiotherapy or radiotherapy alone. Of these, 58 patients were followed at our hospital for at least 4 years. Median clinical follow-up was 79 months. Cardiac toxicity was determined by Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0. The maximum and mean doses to the heart and percentage of the volume were calculated from the dose-volume histograms. SCD manifested in 11 patients. The heart diseases included three pericardial effusions, one pericardial effusion with valvular disease and paroxysmal atrial tachycardia, three atrial fibrillations, one sinus tachycardia, one coronary artery disease, one chest pain with strongly suspected coronary artery disease, and one congestive heart failure. The actual incidence of SCD was 13.8 % at 5 years. Univariate and multivariate analyses of continuous variables revealed that the risk of developing an SCD depended on the volume of the heart receiving a dose greater than 45 Gy (V45), 50 Gy (V50), and 55 Gy (V55). No other clinical factors were found to influence the risk of SCD. For V45, V50, and V55, the lowest significant cutoff values were 15, 10, and 5 %, respectively. High-dose and large-volume irradiation of the heart increased the risk of SCD in long-term survivors. Using modern radiotherapy techniques, it is important to minimize the heart dose-volume parameters without reducing the tumor dose. (orig.) [German] Beurteilung von klinischen und dosimetrischen Faktoren, die mit Risiken eines retrospektiven Auftretens von symptomatischen Herzerkrankungen (SCD) bei Patienten zusammenhaengen, die aufgrund eines Oesophaguskarzinoms strahlentherapeutisch behandelt wurden. Insgesamt 343 Patienten mit neu diagnostiziertem Oesophaguskarzinom wurden mit

Double disadvantage: A case control study on health-related quality of life in children with sickle cell disease.

NARCIS (Netherlands)

Hijmans, C.T.; Fijnvandraat, K.; Oosterlaan, J.; Heijboer, H.; Peters, M.; Grootenhuis, M.A.

2010-01-01

Background: Low health-related quality of life (HRQoL) of children with sickle cell disease (SCD) may be associated with consequences of the disease, or with the low socio-economic status (SES) of this patient population. The aim of this study was to investigate the HRQoL of children with SCD,

Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

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Bravo-Cuellar Alejandro

2008-04-01

Full Text Available Abstract Background Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95 in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Methods Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma. The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L were measured by ELISA kits. Results We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Conclusion Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of

Randomized phase 2 study of GMI-1070 in SCD: reduction in time to resolution of vaso-occlusive events and decreased opioid use

Science.gov (United States)

Wun, Ted; McCavit, Timothy L.; De Castro, Laura M.; Krishnamurti, Lakshmanan; Lanzkron, Sophie; Hsu, Lewis L.; Smith, Wally R.; Rhee, Seungshin; Magnani, John L.; Thackray, Helen

2015-01-01

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833. PMID:25733584

Plasma level of the macrophage-derived soluble CD163 is increased and positively correlates with severity in Gaucher's disease

DEFF Research Database (Denmark)

Møller, Holger Jon; de Fost, Maaike; Aerts, Hans

2004-01-01

Recently, soluble CD163 (sCD163) has been identified as a macrophage/monocyte-specific plasma protein and increased concentrations have been measured in patients with infection and myeloid leukaemia. In the present study we investigated the levels of sCD163 in patients with Gaucher's disease...

The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype

Directory of Open Access Journals (Sweden)

A. Hannemann

2011-01-01

Full Text Available Sickle cell disease (SCD is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12–15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs, containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.

Double disadvantage: a case control study on health-related quality of life in children with sickle cell disease

NARCIS (Netherlands)

Hijmans, Channa T.; Fijnvandraat, Karin; Oosterlaan, Jaap; Heijboer, Harriët; Peters, Marjolein; Grootenhuis, Martha A.

2010-01-01

Low health-related quality of life (HRQoL) of children with sickle cell disease (SCD) may be associated with consequences of the disease, or with the low socio-economic status (SES) of this patient population. The aim of this study was to investigate the HRQoL of children with SCD, controlling for

Apoptosis induction in Jurkat cells and sCD95 levels in women's sera are related with the risk of developing cervical cancer

International Nuclear Information System (INIS)

Aguilar-Lemarroy, Adriana; Jave-Suarez, Luis F; Romero-Ramos, Jose E; Olimon-Andalon, Vicente; Hernandez-Flores, Georgina; Lerma-Diaz, Jose M; Ortiz-Lazareno, Pablo C; Morgan-Villela, Gilberto; Toro-Arreola, Susana del; Bravo-Cuellar, Alejandro

2008-01-01

Currently, there is clear evidence that apoptosis plays an important role in the development and progression of tumors. One of the best characterized apoptosis triggering systems is the CD95/Fas/APO-1 pathway; previous reports have demonstrated high levels of soluble CD95 (sCD95) in serum of patients with some types of cancer. Cervical cancer is the second most common cancer among women worldwide. As a first step in an attempt to design a minimally invasive test to predict the risk of developing cervical cancer in patients with precancerous lesions, we used a simple assay based on the capacity of human serum to induce apoptosis in Jurkat cells. We evaluated the relationship between sCD95 levels and the ability to induce apoptosis in Jurkat cells in cervical cancer patients and controls. Jurkat cells were exposed to serum from 63 women (20 healthy volunteers, 21 with cervical intraepithelial neoplasia grade I [CIN 1] and 22 with cervical-uterine carcinoma). The apoptotic rate was measured by flow cytometry using Annexin-V-Fluos and Propidium Iodide as markers. Serum levels of sCD95 and soluble CD95 ligand (sCD95L) were measured by ELISA kits. We found that serum from almost all healthy women induced apoptosis in Jurkat cells, while only fifty percent of the sera from women with CIN 1 induced cell death in Jurkat cells. Interestingly, only one serum sample from a patient with cervical-uterine cancer was able to induce apoptosis, the rest of the sera protected Jurkat cells from this killing. We were able to demonstrate that elimination of Jurkat cells was mediated by the CD95/Fas/Apo-1 apoptotic pathway. Furthermore, the serum levels of sCD95 measured by ELISA were significantly higher in women with cervical cancer. Our results demonstrate that there is a strong correlation between low levels of sCD95 in serum of normal women and higher apoptosis induction in Jurkat cells. We suggest that an analysis of the apoptotic rate induced by serum in Jurkat cells and the

Pathophysiology and treatment of pulmonary hypertension in sickle cell disease

Science.gov (United States)

Castro, Oswaldo L.; Machado, Roberto F.

2016-01-01

Pulmonary hypertension affects ∼10% of adult patients with sickle cell disease (SCD), particularly those with the homozygous genotype. An increase in pulmonary artery systolic pressure, estimated noninvasively by echocardiography, helps identify SCD patients at risk for pulmonary hypertension, but definitive diagnosis requires right-heart catheterization. About half of SCD-related pulmonary hypertension patients have precapillary pulmonary hypertension with potential etiologies of (1) a nitric oxide deficiency state and vasculopathy consequent to intravascular hemolysis, (2) chronic pulmonary thromboembolism, or (3) upregulated hypoxic responses secondary to anemia, low O2 saturation, and microvascular obstruction. The remainder have postcapillary pulmonary hypertension secondary to left ventricular dysfunction. Although the pulmonary artery pressure in SCD patients with pulmonary hypertension is only moderately elevated, they have a markedly higher risk of death than patients without pulmonary hypertension. Guidelines for diagnosis and management of SCD-related pulmonary hypertension were published recently by the American Thoracic Society. Management of adults with sickle-related pulmonary hypertension is based on anticoagulation for those with thromboembolism; oxygen therapy for those with low oxygen saturation; treatment of left ventricular failure in those with postcapillary pulmonary hypertension; and hydroxyurea or transfusions to raise the hemoglobin concentration, reduce hemolysis, and prevent vaso-occlusive events that cause additional increases in pulmonary pressure. Randomized trials have not identified drugs to lower pulmonary pressure in SCD patients with precapillary pulmonary hypertension. Patients with hemodynamics of pulmonary arterial hypertension should be referred to specialized centers and considered for treatments known to be effective in other forms of pulmonary arterial hypertension. There have been reports that some of these treatments

[Coexisting systemic lupus erythematosus and sickle cell disease: case report and literature review].

Science.gov (United States)

Robazzi, Teresa Cristina M V; Alves, Crésio; Abreu, Laís; Lemos, Gabriela

2015-01-01

To report a case of coexisting systemic lupus erythematosus (SLE) and sickle cell disease (SCD) with a review of the literature on the topic. Report of case and research of the association between SLE and SCD in literature through scientific articles in health sciences databases, such as LILACS, MEDLINE/Pubmed and Scielo, until May 2012. Descriptors used: 1. Sickle cell anemia; 2. Sickle cell disease; 3. Systemic lupus erythematosus; 4. Hemoglobinopathies. The authors describe an association between SLE and SS hemoglobinopathy in an eight-year-old female patient displaying articular, hematologic and neuropsychiatric manifestations during clinical evolution. Forty-five cases of association between SLE and SCD are described in literature, mostly adult (62.2%), women (78%) and with the SS phenotype in 78% of the cases, and different clinical manifestations. Compared with our patient, articular, hematologic and neuropsychiatric manifestations were present in 76%, 36% and 27% of the cases, respectively. SLE and SCD are chronic diseases that have several clinical and laboratory findings in common, meaning difficult diagnosis and difficulty in finding the correct treatment. Although the association between these diseases is not common, it is described in literature, so it is imperative that physicians who treat such diseases be alert to this possibility. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

Decreased plasma levels of soluble CD18 link leukocyte infiltration with disease activity in spondyloarthritis

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Jalilian, Babak; Hvid, Malene

2014-01-01

of arthritis patients to have anti-inflammatory functions. Here, we study the mechanisms for these alterations and their association with SpA disease activity. METHODS: Plasma levels of sCD18 in a study population with 84 SpA patients and matched healthy controls were analyzed with a time resolved......A patients compared with healthy volunteers (P levels in the HLA-B27-positive subgroup (P levels exhibited an inverse correlation with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (P level of morning...... immunoflourometric assay (TRIFMA). Binding of sCD18 to endothelial cells and fibroblast-like synovial cells (FLS) was studied with confocal microscopy. Shedding of CD18 from peripheral blood mononuclear cells (PBMC) was studied with flow cytometry and TRIFMA. RESULTS: Plasma levels of sCD18 were decreased in Sp...

Proceedings of a Sickle Cell Disease Ontology workshop — Towards the first comprehensive ontology for Sickle Cell Disease

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Nicola Mulder

2016-06-01

The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology.

Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease.

Science.gov (United States)

Wilkinson, Katie; Harris, Samantha; Gaur, Prashant; Haile, Askale; Armour, Rosalind; Teramura, Gayle; Delaney, Meghan

2012-02-01

Sickle cell disease (SCD) patients have dissimilar red blood cell (RBC) phenotypes compared to the primarily Caucasian blood donor base due, in part, to underlying complex Rh and silenced Duffy expression. Gene array-based technology offers high-throughput antigen typing of blood donors and can identify patients with altered genotypes. The purpose of the study was to ascertain if RBC components drawn from predominantly Caucasian donors could provide highly antigen-matched products for molecularly typed SCD patients. SCD patients were genotyped by a molecular array (HEA Beadchip, BioArray Solutions). The extended antigen phenotype (C, c, E, e, K, k, Jk(a) , Jk(b) , Fy(a) , Fy(b) , S, s) was used to query the inventory using different matching algorithms; the resulting number of products was recorded. A mean of 96.2 RBC products was available for each patient at basic-level, 34 at mid-level, and 16.3 at high-level stringency. The number of negative antigens correlated negatively with the number of available products. The Duffy silencing mutation in the promoter region (67T>C) (GATA) was found in 96.5% of patients. Allowing Fy(b+) products for patients with GATA increased the number of available products by up to 180%, although it does not ensure prevention of Duffy antibodies in all patients. This feasibility study provides evidence that centers with primarily Caucasian donors may be able to provide highly antigen-matched products. Knowledge of the GATA status expands the inventory of antigen-matched products. Further work is needed to determine the most clinically appropriate match level for SCD patients. © 2012 American Association of Blood Banks.

Relationship of the Content of Systemic and Endobronchial Soluble Molecules of CD25, CD38, CD8, and HLA-I-CD8 and Lung Function Parameters in COPD Patients

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Nailya Kubysheva

2017-01-01

Full Text Available The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.

High prevalence of complementary and alternative medicine use among patients with sickle cell disease in a tertiary hospital in Lagos, South West, Nigeria.

Science.gov (United States)

Busari, A A; Mufutau, M A

2017-06-07

Attention and interest in the use of complementary and alternative medicine (CAM) has been reignited globally, most especially in patients with chronic diseases. Sickle cell disease (SCD) is one of such chronic diseases associated with devastating clinical and psychosocial consequences, thus leading those affected to seek alternative treatment apart from orthodox medicine. Hence, this study aimed to determine the prevalence, pattern and tolerability of the use of CAM in patients with SCD in the Lagos University Teaching Hospital (LUTH). This was a cross-sectional survey of 200 respondents with SCD attending the hematology clinics of the Lagos University Teaching Hospital over a period of 3 months. Data on socio-demographic characteristic, clinical profile, the types and sources of CAM used were collected using a well structured pretested questionnaire. The data obtained were analyzed using Statistical Package for Social Sciences (SPSS®) version 17. Of the 200 patients who participated in the study, 113; 56.5% were males and 87; 43.5% were females. Majority of the SCD patients were 1-10 years old and their mean age was 18.8 ± 14.39 years. CAM was reportedly used by 88.5% of the respondents. Biological (herbal) products 156; 62.9% were the most commonly used CAM, followed by alternative medical systems 52; 20.9% and mind-body interventions 30; 12.1%. Relations, friends and neighbors influenced 85.2% of CAM users by recommending CAM to them. Tolerability of CAM was perceived to be excellent as only 33 (18.6%) of the respondents abandoned the use of CAM. Comparing CAM users and CAM non-users, there was no statistical significant difference in the proportion of those >18 years (45.76% vs 52.17%; p = 0.658), those who experienced two or more crises (51.41% vs 34.78%; p = 0.183), and those with stable haemoglobin concentration of >7 g/dL (15.81% vs 8.69%; p = 0.539) More patients among CAM non-users (91.30%) significantly spend over 3000 Naira (USD 15) per

Comparison of Tc-99m Ciprofloxacin (Infecton) and Tc-99m Methylene diphosphonate (MDP) three-phase bone scintigraphy in the diagnosis of osteomyelitis in patients with Sickle Cell Disease

International Nuclear Information System (INIS)

Bererhi, H.; Hussein, S.; Wali, Y.

2003-01-01

The high incidence of Sickle Cell Disease (SCD) is a major health problem in Oman. These patients are more prone to infections than the general population, and in particular, they are highly susceptible to osteomyelitis. Because bone infarction is more common than osteomyelitis in SCD, an accurate and rapid differential diagnosis is essential before initiating appropriate treatment. The present prospective study evaluates the usefulness of the new radiopharmaceutical, Tc- 99m Ciprofloxacin (Infecton) for the differential diagnosis of infection and infarction in patients with SCD. Majority of subjects studied were children. The results of Tc-99m Infecton imaging were compared with those of the 3-phase bone scintigraphy using Tc- 99m Methylene diphosphonate (Tc-99m MDP). Twenty-five patients referred for ruling out infection were imaged after intravenous injection of 5.5 MBq/kg body weight of Tc-99m Infecton. First pass, blood pool and late images (at one, four and 24 hours post injection) were performed. Subsequently all patients were also studied by three-phase bone scintigraphy using Tc-99m MDP. No adverse effects were observed. The sensitivity, specificity, accuracy and positive likelihood ratio of Tc-99m Infecton imaging for osteomyelitis were 100%, 92%, 94% and 12.5 respectively. Although bone scintigraphy would rarely be used by itself as a stand-alone test in the diagnosis of osteomyelitis in patients with SCD, its corresponding values were: 88%, 64%, 71% and 2.4. The results of this study suggest that the use of Tc-99m Infecton imaging is extremely beneficial in the management of patients of Sickle Cell Disease with suspected osteomyelitis. (author)

Prospective radiological study concerning a series of patients suffering from conductive or mixed hearing loss due to superior semicircular canal dehiscence.

Science.gov (United States)

Martin, Christian; Chahine, Pierre; Veyret, Charles; Richard, Céline; Prades, Jean Michel; Pouget, Jean François

2009-08-01

The aim of this study is to appreciate the incidence of patients with isolated conductive hearing loss with normal drum due to superior semicircular canal dehiscence (SCD). It is a prospective radiological study. Two hundred and seventy-two patients with a normal drum suffering from isolated unilateral or bilateral conductive or mixed hearing loss were included in a prospective radiological study. A high resolution computerized tomography (HRCT) was performed in all the patients. Those who were found to have a unilateral or bilateral SCD underwent further etiological, clinical, audiologic evaluation. Ten patients with conductive or mixed hearing loss were found to have a unilateral or bilateral SCD. The disease was bilateral in five cases, and most often associated with a dehiscence of the tegmen tympani on both sides, supporting the theory of the congenital nature of the disease. There was no clear correlation between symptoms and the size of the SCD. Because patients were not suffering from incapacitating vestibular symptoms, they were not operated for surgical occlusion of the SCD, and were referred to a hearing aid specialist to improve hearing. Conductive or mixed hearing loss due to SCD is relatively frequent, justifying in our opinion that a systematic HRCT be carried out before surgery of any patient with conductive hearing loss.

Semantic memory and depressive symptoms in patients with subjective cognitive decline, mild cognitive impairment, and Alzheimer's disease.

Science.gov (United States)

Lehrner, J; Coutinho, G; Mattos, P; Moser, D; Pflüger, M; Gleiss, A; Auff, E; Dal-Bianco, P; Pusswald, G; Stögmann, E

2017-07-01

Semantic memory may be impaired in clinically recognized states of cognitive impairment. We investigated the relationship between semantic memory and depressive symptoms (DS) in patients with cognitive impairment. 323 cognitively healthy controls and 848 patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia were included. Semantic knowledge for famous faces, world capitals, and word vocabulary was investigated. Compared to healthy controls, we found a statistically significant difference of semantic knowledge in the MCI groups and the AD group, respectively. Results of the SCD group were mixed. However, two of the three semantic memory measures (world capitals and word vocabulary) showed a significant association with DS. We found a difference in semantic memory performance in MCI and AD as well as an association with DS. Results suggest that the difference in semantic memory is due to a storage loss rather than to a retrieval problem.

A Cross-Sectional Study of the Prevalence of Gastrointestinal Symptoms and Pathology in Patients With Common Variable Immunodeficiency.

Science.gov (United States)

Jørgensen, Silje F; Reims, Henrik M; Frydenlund, Didrik; Holm, Kristian; Paulsen, Vemund; Michelsen, Annika E; Jørgensen, Kristin K; Osnes, Liv T; Bratlie, Jorunn; Eide, Tor J; Dahl, Christen P; Holter, Ellen; Tronstad, Rune R; Hanevik, Kurt; Brattbakk, Hans-Richard; Kaveh, Fatemeh; Fiskerstrand, Torunn; Kran, Anne-Marte B; Ueland, Thor; Karlsen, Tom H; Aukrust, Pål; Lundin, Knut E A; Fevang, Børre

2016-10-01

The objective of this study was to study the prevalence of gastrointestinal (GI) symptoms and histopathology in patients with common variable immunodeficiency (CVID) as well as linking the findings to GI infections and markers of systemic immune activation. In this cross-sectional study, we addressed GI symptoms in 103 patients and GI histopathological findings in 53 patients who underwent upper and lower endoscopic examination. The most frequent histopathological findings were linked to GI symptoms, B-cell phenotype, and markers of systemic immune activation (soluble (s)CD14, sCD25, and sCD163). Microarray analysis compared "celiac-like disease" in CVID to celiac disease. Screening for selected bacterial and viral infections in fecal samples and gut mucosal biopsies was performed. The main findings of this study were as follows: most common GI symptoms were bloating (34%), pain (30%), and diarrhea (26%). The most frequent histopathological findings were increased intraepithelial lymphocytes in the descending part of the duodenum, i.e., "celiac-like disease" (46% of patients), decreased numbers of plasma cells in GI tract mucosa (62%), and lymphoid hyperplasia (38%), none of which were associated with GI symptoms. Reduced plasma cells in GI mucosa were associated with B-cell phenotypic characteristics of CVID, and increased serum levels of sCD14 (P=0.025), sCD25 (P=0.01), and sCD163 (P=0.04). Microarray analyses distinguished between CVID patients with "celiac-like disease" and celiac disease. Positive tests for bacterial and viral infections were scarce both in fecal samples and gut mucosal biopsies, including PCR test for norovirus in biopsy specimens (0 positive tests). In conclusion, GI pathology is common in CVID, but does not necessarily cause symptoms. However, reduced plasma cells in GI mucosa were linked to systemic immune activation, "celiac-like disease" in CVID and true celiac disease appear to be different disease entities, as assessed by gene

Serum Levels of Platelet Released CD40 Ligand Are Increased in Early Onset Occlusive Carotid Artery Disease

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József Balla

2006-01-01

Full Text Available Objective: Soluble CD40 ligand (sCD40L has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls.

Anaesthetic implications of laparoscopic splenectomy in patients with sickle cell anaemia.

LENUS (Irish Health Repository)

Doodnath, R.

2010-04-01

With the increasing immigrant population in the Republic of Ireland, the number of patients with sickle cell disease (SCD) seen in the paediatric hospitals is climbing. In this case report, we review the anaesthetic implications and outcome of the first two paediatric patients with SCD to have a laparoscopic splenectomy due to repeated splenic infarcts in the Republic of Ireland.

Anaesthetic implications of laparoscopic splenectomy in patients with sickle cell anaemia.

LENUS (Irish Health Repository)

Doodnath, R

2012-02-01

With the increasing immigrant population in the Republic of Ireland, the number of patients with sickle cell disease (SCD) seen in the paediatric hospitals is climbing. In this case report, we review the anaesthetic implications and outcome of the first two paediatric patients with SCD to have a laparoscopic splenectomy due to repeated splenic infarcts in the Republic of Ireland.

Environmental Influences on Daily Emergency Admissions in Sickle-Cell Disease Patients

Science.gov (United States)

Mekontso Dessap, Armand; Contou, Damien; Dandine-Roulland, Claire; Hemery, François; Habibi, Anoosha; Charles-Nelson, Anaïs; Galacteros, Frederic; Brun-Buisson, Christian; Maitre, Bernard; Katsahian, Sandrine

2014-01-01

Abstract Previous reports have suggested a role for weather conditions and air pollution on the variability of sickle cell disease (SCD) severity, but large-scale comprehensive epidemiological studies are lacking. In order to evaluate the influence of air pollution and climatic factors on emergency hospital admissions (EHA) in SCD patients, we conducted an 8-year observational retrospective study in 22 French university hospitals in Paris conurbation, using distributed lag non-linear models, a methodology able to flexibly describe simultaneously non-linear and delayed associations, with a multivariable approach. During the 2922 days of the study, there were 17,710 EHA, with a mean daily number of 6.1 ± 2.8. Most environmental factors were significantly correlated to each other. The risk of EHA was significantly associated with higher values of nitrogen dioxide, atmospheric particulate matters, and daily mean wind speed; and with lower values of carbon monoxide, ozone, sulfur dioxide, daily temperature (minimal, maximal, mean, and range), day-to-day mean temperature change, daily bright sunshine, and occurrence of storm. There was a lag effect for 12 of 15 environmental factors influencing hospitalization rate. Multivariate analysis identified carbon monoxide, day-to-day temperature change, and mean wind speed, along with calendar factors (weekend, summer season, and year) as independent factors associated with EHA. In conclusion, most weather conditions and air pollutants assessed were correlated to each other and influenced the rate of EHA in SCD patients. In multivariate analysis, lower carbon monoxide concentrations, day-to-day mean temperature drop and higher wind speed were associated with increased risk of EHA. PMID:25546672

Translating scientific advances to improved outcomes for children with sickle cell disease: a timely opportunity.

Science.gov (United States)

Raphael, Jean L; Kavanagh, Patricia L; Wang, C Jason; Mueller, Brigitta U; Zuckerman, Barry

2011-07-01

Despite the recent advances made in the care of children with sickle cell disease (SCD), premature mortality, especially among older children and young adults, remains a hallmark of this disease. The lack of survival gains highlights the translational gap of implementing innovations found efficacious in the controlled trial setting into routine clinical practice. Health services research (HSR) examines the most effective ways to finance, organize, and deliver high quality care in an equitable manner. To date, HSR has been underutilized as a means to improve the outcomes for children with SCD. Emerging national priorities in health care delivery, new sources of funding, and evolving electronic data collection systems for patients with SCD have provided a unique opportunity to overcome the translational gap in pediatric SCD. The purpose of this article is to provide a comprehensive HSR agenda to create patient-specific evidence of clinical effectiveness for interventions used in the routine care setting, understand the barriers faced by clinicians to providing high quality care, assess and improve the interactions of patients with the health care system, and measure the quality of care delivered to increase survival for all children and young adults with SCD. Copyright © 2011 Wiley-Liss, Inc.

Parsing the Dictionary of Modern Literary Russian Language with the Method of SCD Configurations. The Lexicographic Modeling

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Neculai Curteanu

2012-05-01

Full Text Available This paper extends the experience of parsing other five, sensibly different, Romanian, French, and German largest dictionaries, to \\textbf{\\textit{DMLRL}} (Dictionary of Modern Literary Russian Language [18], using the optimal and portable parsing method of SCD (Segmentation-Cohesion-Dependency configurations [7], [11], [15]. The purpose of the present paper is to elaborate the lexicographic modeling of \\textbf{\\textit{DMLRL}}, which necessarily precedes the sense tree parsing dictionary entries. The following \\textbf{\\textit{three}} SCD configurations are described: the \\textbf{\\textit{first one}} has to separate the lexicographic segments in a \\textbf{\\textit{DMLRL}} entry, the \\textbf{\\textit{second}} SCD-configuration concentrates on the SCD marker classes and their hypergraph hierarchy for \\textbf{\\textit{DMLRL}} primary and secondary senses, while the \\textbf{\\textit{third}} SCD configuration hands down the same modeling process to the atomic sense definitions and their examples-to-definitions. The dependency hypergraph of the third SCD configuration, interconnected to the one of the second SCD configuration, is specified completely at the atomic sense level for the first time, exceeding the SCD configuration modeling for other five dictionaries [15], [14]. Numerous examples from \\textbf{\\textit{DMLRL}} and comparison to \\textbf{\\textit{DLR-DAR}} Romanian thesaurus-dictionary support the proposed \\textbf{\\textit{DMLRL}} lexicographic modeling.

Pattern of referral of noncancer patients to palliative care in the Eastern province of Saudi Arabia

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Hafez M Ghanem

2011-01-01

Results : From 474 patients, 20 (4.2% had a noncancer diagnosis. The main reason for the referral of noncancer patients was pain control. The most prevalent diagnoses were sickle cell disease (SCD in 6 (30% patients and peripheral arterial disease (PAD in 5 (25%. Conclusions : These findings suggest that the PC needs of noncancer patients are largely unmet in our region. Further efforts are necessary to advance noncancer PC in Saudi Arabia. The PC needs of patients with SCD and PAD need to be addressed in future research.

Real-life experience with hydroxyurea in sickle cell disease: A multicenter study in a cohort of patients with heterogeneous descent.

Science.gov (United States)

Rigano, Paolo; De Franceschi, Lucia; Sainati, Laura; Piga, Antonio; Piel, Frédéric B; Cappellini, Maria Domenica; Fidone, Carmelo; Masera, Nicoletta; Palazzi, Giovanni; Gianesin, Barbara; Forni, Gian Luca

2018-03-01

We conducted the first nation-wide cohort study of sickle cell disease (SCD) in Italy, a Southern European country exposed to intense recent flux migration from endemic areas for SCD. We evaluate the impact of hydroxyurea on a total of 652 pediatric and adult patients from 33 Reference Centers for SCD (mean age 24.5±15years, 51.4% males). Hydroxyurea median treatment duration was 7years (range: crisis (-34.1%, p<0.001), hospitalization (-53.2%, p<0.001), and bone necrosis (-6.9%, p<0.001). New silent cerebral infarction (SCI) occurred during treatment (+42.4%, p<0.001) but not stroke (+0.5%, p=0.572). These observations were generally consistent upon stratification for age, descent (Caucasian or African), genotype (βS/βS, βS/β 0 or βS/β + ) and duration of treatment (< or ≥10years). There were no new safety concerns observed compared to those commonly reported in the literature. Our study, conducted on a large population of patients with different descent and compound state supports the benefits of hydroxyurea therapy as a treatment option. Registered at clinical trials.gov (NCT02709681). Copyright © 2017 Elsevier Inc. All rights reserved.

Sickle cell disease in childhood in Madina

International Nuclear Information System (INIS)

Hawasawi, Zakaria M.; Nabi, G.; Al-Magamci, M.S.F.; Awad, Khalid S.

1998-01-01

Sickle cell disease (SCD) is a common disease in Saudi Arabia, with ahigh prevalence in the Eastern and Southern regions. This study reports on 53cases of SCD encountered in the Madina area. In a retrospective study of 6000pediatric patients, 53 children (0.88%) with sickle cell disease wereadmitted in the Maternity and Children's Hospital Madina, between November1990 and October 1991. Of these, 39 patients (73.58%) were Saudis and 14(26.41%) were non-Saudis. Thirty-six patients were homozygous SS and 17 weresickle thalassemic. The main causes of admission were vaso-occlusive crisis(77.35%), infection (67.92%), acute chest syndrome (22.64%), anemia (12.6%)and cerebrovascular accident (9.43%). The lowest and highest age groupsrecorded in this study were six months and 12 years, respectively. About 70%of patients are still being followed-up, and none of the patients has died.This disease is one of the major causes of morbidity in this region of SaudiArabia. Measures required include neonatal screening programs for the earlydetection of the disease as well as research into new drugs to counter thedisease. (author)

Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

NARCIS (Netherlands)

van der Dijs, Fey P L; Fokkema, M Rebecca; Dijck-Brouwer, D A Janneke; Niessink, Bram; van der Wal, Thaliet I C; Schnog, John-John B; Duits, Ashley J; Muskiet, Fred D; Muskiet, Frits A J

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and

Levels of high-density lipoprotein cholesterol (HDL-C among children with steady-state sickle cell disease

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Seixas Magda O

2010-08-01

Full Text Available Abstract Background The search for sickle cell disease (SCD prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.

MANAGEMENT OF SICKLE CELL DISEASE

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Rajesh

2016-02-01

Full Text Available Sickle cell disease (SCD is a genetically transmitted multisystem disease1 which includes a group of disorders that differs in severity sign and symptoms, The disease is not uniformly seen everywhere but it has some topographical distribution. In India, it is frequently seen in Central India, in and around the vicinity of Chhattisgarh in some religions in caste like kurmis, satnami, mahar, other backward caste and some tribes, it has great pathological significance considering the high morbidity and mortality resulting from the disease process. We have studied the cases of SCD from 2001 to 2015 series of such patients, since there is no cure of this disease, in regards to prevention of this genetic autosomal recessive disorder by marriage counseling, the incidence can be significantly reduced by avoiding consanguineous marriages in the susceptible community.

Red blood cell alloimmunization in patients with sickle cell disease in Turkey: a single center retrospective cohort study

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Soner Solmaz

2016-12-01

Results: Of 216 SCD patients included in the study. Alloimmunization was detected in 67 (31.0% out of 216 patients who underwent transfusion, and in 17 (30.4% out of 56 patients in Group 1 and in 50 (31.3% out of 160 patients in Group 2. When the patients were analyzed according to alloimmunization development, our study revealed that neither SCD complications are a risk factor for alloimmunization nor alloimmunization increases mortality rates. Conclusion: High alloimmunization frequency found in our study suggests the insufficient adherence of alloimmunization-prevention policies in RBC transfusions performed except experienced institutions. Therefore alloimmunization may be reduced or prevented through performing extended red cell typing among SCD patients. [Cukurova Med J 2016; 41(4.000: 622-627

School Performance and Disease Interference in Adolescents with Sickle Cell Disease

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Crosby, Lori E.; Joffe, Naomi E.; Irwin, Mary Kay; Strong, Heather; Peugh, James; Shook, Lisa; Kalinyak, Karen A.; Mitchell, Monica J.

2015-01-01

Sickle cell disease (SCD) results in neuropsychological complications that place adolescents at higher risk for limited educational achievement. A first step to developing effective educational interventions is to understand the impact of SCD on school performance. The current study assessed perceptions of school performance, SCD interference and…

Differences in pain management between hematologists and hospitalists caring for patients with sickle cell disease hospitalized for vasoocclusive crisis.

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Shah, Nirmish; Rollins, Margo; Landi, Daniel; Shah, Radhika; Bae, Jonathan; De Castro, Laura M

2014-03-01

Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by hospitalists. The purpose of this study is to examine differences in pain management between hematologists and hospitalists. We performed a single-institution, retrospective review of pain management patterns and outcomes in adult SCD patients hospitalized for vaso-occlusive crisis. Over 26 months, we found a total of 298 patients (120 cared for by the hematologists and 178 by hospitalists), with a mean age of 32 (range 19-58). Patients cared for by hospitalists had a lower total number of hours on a patient controlled analgesia (PCA) device (171 vs. 212 hours, P=0.11). Hospitalists also were significantly more likely to utilize demand only PCA (42% vs. 23%, P=0.002) and had a significantly lower rate of using both continuous and demand PCA (54% vs. 67%, P=0.04). In addition, patients cared for by hospitalists had a significantly shorter hospitalization (8.4 days) compared to hematologists (10 days, P=0.04) with a non-significant difference in 7 and 30 day readmission rates (7.2% vs. 6.7% and 40% vs. 35% respectively). We found patients cared for by hospitalists more frequently utilized home oral pain medication during admission, had shorter lengths of hospitalization, and did not have a significant increase in readmission rates.

Sickle cell disease and complex congenital cardiac surgery: a case report and review of the pathophysiology and perioperative management.

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Sanders, D B; Smith, B P; Sowell, S R; Nguyen, D H; Derby, C; Eshun, F; Nigro, J J

2014-03-01

Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the β-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.

SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

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Paul Mason

Full Text Available Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway.

SCD1 inhibition causes cancer cell death by depleting mono-unsaturated fatty acids.

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Mason, Paul; Liang, Beirong; Li, Lingyun; Fremgen, Trisha; Murphy, Erin; Quinn, Angela; Madden, Stephen L; Biemann, Hans-Peter; Wang, Bing; Cohen, Aharon; Komarnitsky, Svetlana; Jancsics, Kate; Hirth, Brad; Cooper, Christopher G F; Lee, Edward; Wilson, Sean; Krumbholz, Roy; Schmid, Steven; Xiang, Yibin; Booker, Michael; Lillie, James; Carter, Kara

2012-01-01

Increased metabolism is a requirement for tumor cell proliferation. To understand the dependence of tumor cells on fatty acid metabolism, we evaluated various nodes of the fatty acid synthesis pathway. Using RNAi we have demonstrated that depletion of fatty-acid synthesis pathway enzymes SCD1, FASN, or ACC1 in HCT116 colon cancer cells results in cytotoxicity that is reversible by addition of exogenous fatty acids. This conditional phenotype is most pronounced when SCD1 is depleted. We used this fatty-acid rescue strategy to characterize several small-molecule inhibitors of fatty acid synthesis, including identification of TOFA as a potent SCD1 inhibitor, representing a previously undescribed activity for this compound. Reference FASN and ACC inhibitors show cytotoxicity that is less pronounced than that of TOFA, and fatty-acid rescue profiles consistent with their proposed enzyme targets. Two reference SCD1 inhibitors show low-nanomolar cytotoxicity that is offset by at least two orders of magnitude by exogenous oleate. One of these inhibitors slows growth of HCT116 xenograft tumors. Our data outline an effective strategy for interrogation of on-mechanism potency and pathway-node-specificity of fatty acid synthesis inhibitors, establish an unambiguous link between fatty acid synthesis and cancer cell survival, and point toward SCD1 as a key target in this pathway.

Chronic complications and quality of life of patients living with sickle cell disease and receiving care in three hospitals in Cameroon: a cross-sectional study.

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Andong, Anne M; Ngouadjeu, Eveline D T; Bekolo, Cavin E; Verla, Vincent S; Nebongo, Daniel; Mboue-Djieka, Yannick; Choukem, Simeon-Pierre

2017-01-01

Sickle Cell Disease (SCD) is associated with chronic multisystem complications that significantly influence the quality of life (QOL) of patients early in their life. Although sub-Saharan Africa bears 75% of the global burden of SCD, there is a paucity of data on these complications and their effects on the QOL. We aimed to record these chronic complications, to estimate the QOL, and to identify the corresponding risk factors in patients with SCD receiving care in three hospitals in Cameroon. In this cross-sectional study, a questionnaire was used to collect data from consecutive consenting patients. Information recorded included data on the yearly frequency of painful crisis, the types of SCD, and the occurrence of chronic complications. A 36-Item Short Form (SF-36) standard questionnaire that examines the level of physical and mental well-being, was administered to all eligible participants. Data were analyzed with STATA® software. Of 175 participants included, 93 (53.1%) were female and 111 (aged ≥14 years) were eligible for QOL assessment. The median (interquartile range, IQR) age at diagnosis was 4.0 (2.0-8.0) years and the median (IQR) number of yearly painful crisis was 3.0 (1.0-7.0). The most frequent chronic complications reported were: nocturnal enuresis, chronic leg ulcers, osteomyelitis and priapism (30.9%, 24.6%, 19.4%, and 18.3% respectively). The prevalence of stroke and avascular necrosis of the hip were 8.0% and 13.1% respectively. The median (IQR) physical and mental scores were 47.3 (43.9-58.5) and 41.0 (38.8-44.6) respectively. Age and chronic complications such as stroke and avascular necrosis were independently associated with poor QOL. In this population of patients living with SCD, chronic complications are frequent and their QOL is consequently poor. Our results highlight the need for national guidelines for SCD control, which should include new-born screening programs and strategies to prevent chronic complications.

Rapid-rate nonsustained ventricular tachycardia found on implantable cardioverter-defibrillator interrogation: relationship to outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).

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Chen, Jay; Johnson, George; Hellkamp, Anne S; Anderson, Jill; Mark, Daniel B; Lee, Kerry L; Bardy, Gust H; Poole, Jeanne E

2013-05-28

The aim of this study was to examine rapid-rate nonsustained ventricular tachycardia (RR-NSVT) during routine implantable cardioverter-defibrillator (ICD) evaluation in patients with heart failure and its relationship to outcomes. The clinical implications of RR-NSVT identified during routine ICD interrogation are unclear. In this study, the occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were examined. The 811 patients who received ICDs in SCD-HeFT constituted the study population. The occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT were examined. RR-NSVT was documented on ICD interrogation in 186 of 811 patients (22.9%). The mean duration of RR-NSVT was 26.4 ± 9.1 beats (7.5 ± 2.6 s), with a mean cycle length of 259 ± 32 ms. Polymorphic RR-NSVT accounted for 56% of episodes. Compared with patients without RR-NSVT, those with RR-NSVT were less likely to be taking beta-blockers, statins, or aspirin at enrollment. After adjusting for other known predictors of mortality in SCD-HeFT, RR-NSVT was independently associated with appropriate ICD shocks (hazard ratio: 4.25; 95% confidence interval: 2.94 to 6.14; p interrogation should be considered an important clinical event. RR-NSVT during ICD interrogation is associated with appropriate ICD shocks and all-cause mortality. The clinical evaluation of patients with RR-NSVT should include intensification of medical therapy, particularly beta-blockers, or other appropriate clinical interventions. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609). Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Iron deposition in cranial bone marrow with sickle cell disease: MR assessment using a fat suppression technique

International Nuclear Information System (INIS)

Kaneko, K.; Humbert, J.H.; Kogutt, M.S.; Robinson, A.E.

1993-01-01

Thirteen patients with sickle cell disease (SCD) undergoing transfusion therapy and 8 control patients were examined by magnetic resonance imaging to discriminate bone marrow change due to iron deposition from hematologic marrow hyperplasia. Using T1-weighted spin echo images, only two subjects showed extremely low signal intensity marrow compatible with iron deposition. However, using T2-weighted fast spin echo images with fat suppression, cranial bone marrow in SCD patients with transfusion therapy showed considerably lower signal than that of controls. The main cause of marrow signal decrease in SCD patients with transfusion therapy was considered to be iron deposition due to repeated transfusion therapy rather than red marrow hyperplasia. (orig.)

Turf wars: exploring splenomegaly in sickle cell disease in malaria-endemic regions.

Science.gov (United States)

Tubman, Venée N; Makani, Julie

2017-06-01

Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity and mortality around the world. While decades of research have led to improved survival for SCD patients in wealthy countries, survival remains dismal in low- and middle-income countries. Much of the early mortality associated with SCD is attributed to increased risk of infections due to early loss of splenic function. In the West, bacterial infections with encapsulated organisms are a primary concern. In sub-Saharan Africa, where the majority of infants with SCD are born, the same is true. However malaria presents an additional threat to survival. The search for factors that define variability in sickle cell phenotypes should include environmental modifiers, such as malaria. Further exploration of this relationship could lead to novel strategies to reduce morbidity and mortality attributable to infections. In this review, we explore the interactions between SCD, malaria and the spleen to better understand how splenomegaly and splenic (dys)function may co-exist in patients with SCD living in malaria-endemic areas. © 2017 John Wiley & Sons Ltd.

Expression and Association of SCD Gene Polymorphisms and Fatty Acid Compositions in Chicken Cross

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A. Furqon

2017-12-01

Full Text Available Stearoyl-CoA desaturase (SCD is an integral membrane protein of endoplasmic reticulum (ER that catalyzes the rate limiting step in the monounsaturated fatty acids from saturated fatty acids. Selection for fatty acids traits based on molecular marker assisted selection is needed to increase a value of chicken meat. This study was designed to analyze expression and associations of SCD gene polymorphisms with fatty acid traits in F2 kampung-broiler chicken cross. A total of 62 F2 kampung-broiler chicken cross (29 males and 33 females were used in this study. Fatty acid traits were measured at 26 weeks of age. Samples were divided into two groups based on fatty acid traits (the highest and the lowest. Primers in exon 2 region were designed from the genomic chicken sequence. The SNP g.37284A>G was detected and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP method was then used to genotype. The expression of SCD gene was analyzed using quantitative real time PCR (qRT-PCR. The result showed that there were three genotypes (AA, AG, and GG found in this study. The SCD|AciI polymorphism was significantly associated with palmitoleic acid (C16:1, fatty acids total and saturated fatty acid in 26 weeks old of F2 kampung-broiler chicken cross (P<0.05. The SCD gene was expressed for polyunsaturated fatty acids in liver tissue in two groups of chickens. In conclusion, the SCD gene could be a candidate gene that affects fatty acids traits in F2 kampung-broiler chicken cross.

Knowledge insufficient: the management of haemoglobin SC disease.

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Pecker, Lydia H; Schaefer, Beverly A; Luchtman-Jones, Lori

2017-02-01

Although haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence-based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC. © 2016 John Wiley & Sons Ltd.

Chronic kidney disease is common in sickle cell disease: a cross-sectional study in the Tema Metropolis, Ghana.

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Ephraim, Richard Kobina Dadzie; Osakunor, Derick Nii Mensah; Cudjoe, Obed; Oduro, Enos Amoako; Asante-Asamani, Lyudmila; Mitchell, Juliana; Agbodzakey, Hope; Adoba, Prince

2015-05-29

Renal involvement in sickle cell disease (SCD) contributes significantly to morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease (CKD) amongst SCD patients, and how basic clinical variables differ across haemoglobin genotypes. A hospital-based cross-sectional study conducted from December 2013 to May 2014 at the Sickle cell clinic of the Tema General Hospital. One hundred and ninety-four (194) participants with SCD, receiving medical care at the outpatient sickle cell clinic were enrolled onto the study. A structured questionnaire was administered to obtain information on demography, clinical history, blood pressure and anthropometry. Blood and urine samples were taken for serum creatinine and proteinuria determination respectively. The estimated GFR (eGFR) was calculated using the CKD-EPI and Schwartz equations. CKD was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Analysis was performed using GraphPad prism and P <0.05 was considered statistically significant. CKD was present in 39.2% of participants. Using KDIGO guidelines, 40.8% of the HbSS participants had stage 1 CKD and none had stage 2 CKD. In addition, 30.8% of the HbSC participants had stage 1 CKD and 3.8% had stage 2 CKD. There was a trend of increasing age across CKD stages and stage 2 CKD participants were oldest (P < 0.001). Results from the current study suggest that CKD is common amongst SCD patients and prevalence and intensity increases with age. Proteinuria and CKD was more common in HbSS genotype than in HbSC genotype.

SCD1 Confers Temozolomide Resistance to Human Glioma Cells via the Akt/GSK3β/β-Catenin Signaling Axis

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Shuang Dai

2018-01-01

Full Text Available Resistance to temozolomide (TMZ, the standard chemotherapy agent for glioblastoma (GBM, poses a major clinical challenge to GBM prognosis. Understanding the mechanisms of TMZ resistance can help to identify novel drug targets and more effective therapies. Recent studies suggest that bioenergetic alterations of cancer cells play important roles in drug resistance. In our study, the altered metabolism of cancer cells was observed using a metabolic PCR array. We found that stearoyl-coenzyme A desaturase 1 (SCD1, a key rate-limiting enzyme for synthesis of monounsaturated fatty acids, was significantly upregulated in TMZ-resistant GBM cells compared to their parental counterparts. Overexpression of SCD1 promoted resistance to TMZ in parental GBM cells, whereas SCD1 downregulation by siRNA could re-sensitize TMZ-resistant cells in vitro. Combinational treatment of TMZ and an SCD1-specific inhibitor showed a combined inhibitory effect on TMZ-resistant glioma cells. We also observed that overexpression of SCD1 promoted Akt/GSK3β/β-catenin signaling, while silencing of SCD1 inhibited the signaling. The combination of an Akt activator with exogenous SCD1 or the combined inhibition of Akt and enforced expression of SCD1 resulted in the most significant changes of Akt signaling. Functionally, significantly lower viability and mobility rates were observed in TMZ-resistant cells when treated with Akt inhibitors and an SCD1 inhibitor simultaneously compared to when treated individually. In conclusion, our study identified SCD1 along with its functional pathway as a novel target in the development of TMZ resistance. SCD1 inhibition used alone or in combination with Akt inhibition could effectively overcome TMZ resistance in gliomas.

Impairment of myocardial perfusion in children with sickle cell disease

International Nuclear Information System (INIS)

Maunoury, C.; Acar, P.; Montalembert, M. de

2003-01-01

While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 ± 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 ± 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

Three family members with elevated plasma cobalamin, transcobalamin and soluble transcobalamin receptor (sCD320)

DEFF Research Database (Denmark)

Hoffmann-Lücke, Elke; Arendt, Johan F B; Nissen, Peter H

2013-01-01

deficiency were found. DNA sequencing of the TCN2 gene revealed several known polymorphisms not associated with highly elevated transcobalamin levels. Upon gel filtration, sCD320 eluted as a larger molecule than previously reported. By incubation with anti-transcobalamin antibodies, we precipitated both...... transcobalamin and part of sCD320. CONCLUSIONS: The high cobalamin levels were mainly explained by high levels of holoTC, possibly caused by complex formation with its soluble receptor, sCD320. The family occurrence points to a genetic explanation....

A randomized trial of artesunate-amodiaquine versus artemether-lumefantrine in Ghanaian paediatric sickle cell and non-sickle cell disease patients with acute uncomplicated malaria

DEFF Research Database (Denmark)

Adjei, George O; Goka, Bamenla Q; Enweronu-Laryea, Christabel C

2014-01-01

of the SCD patients were also compared with a group of malaria-negative SCD children (n = 82) in steady state. RESULTS: The parasite densities on admission were significantly lower in the SCD group, compared with the non-SCD group (p = 0.0006). The parasite reduction ratio (PRR) was lower, clearance....../57) in the SCD group and 96.4% (53/55) in the non-SCD group. The fractional changes in haemoglobin, platelets and white blood cell counts between baseline (day 0) and endpoint (day 42) were 16.9, 40.6 and 92.3%, respectively, for the SCD group, and, 12.3, 48.8 and 7.5%, respectively, for the non-SCD group....... There were no differences in these indices between AA- and AL-treated subjects. CONCLUSIONS: The parasite clearance of SCD children with uncomplicated malaria was slower compared with non-SCD children. AA and AL showed similar clinical and parasitological effects in the SCD and non-SCD groups...

The effect of hypnosis on pain and peripheral blood flow in sickle-cell disease: a pilot study

Science.gov (United States)

Bhatt, Ravi R; Martin, Sarah R; Evans, Subhadra; Lung, Kirsten; Coates, Thomas D; Zeltzer, Lonnie K; Tsao, Jennie C

2017-01-01

Background Vaso-occlusive pain crises (VOCs) are the “hallmark” of sickle-cell disease (SCD) and can lead to sympathetic nervous system dysfunction. Increased sympathetic nervous system activation during VOCs and/or pain can result in vasoconstriction, which may increase the risk for subsequent VOCs and pain. Hypnosis is a neuromodulatory intervention that may attenuate vascular and pain responsiveness. Due to the lack of laboratory-controlled pain studies in patients with SCD and healthy controls, the specific effects of hypnosis on acute pain-associated vascular responses are unknown. The current study assessed the effects of hypnosis on peripheral blood flow, pain threshold, tolerance, and intensity in adults with and without SCD. Subjects and methods Fourteen patients with SCD and 14 healthy controls were included. Participants underwent three laboratory pain tasks before and during a 30-minute hypnosis session. Peripheral blood flow, pain threshold, tolerance, and intensity before and during hypnosis were examined. Results A single 30-minute hypnosis session decreased pain intensity by a moderate amount in patients with SCD. Pain threshold and tolerance increased following hypnosis in the control group, but not in patients with SCD. Patients with SCD exhibited lower baseline peripheral blood flow and a greater increase in blood flow following hypnosis than controls. Conclusion Given that peripheral vasoconstriction plays a role in the development of VOC, current findings provide support for further laboratory and clinical investigations of the effects of cognitive–behavioral neuromodulatory interventions on pain responses and peripheral vascular flow in patients with SCD. Current results suggest that hypnosis may increase peripheral vasodilation during both the anticipation and experience of pain in patients with SCD. These findings indicate a need for further examination of the effects of hypnosis on pain and vascular responses utilizing a randomized

[Evaluation of immune status of kidney transplant recipients by combined HLA-G5 and sCD30].

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JIN, Zhan-kui; TIAN, Pu-xun; XUE, Wu-jun; DING, Xiao-ming; PAN, Xiao-ming; DING, Chen-guang; JIA, Li-ning; GE, Guan-qun; HAO, Jun-jun

2010-09-28

to study the relationship between the expression of serum human leucocyte antigen-G5 (HLA-G5)/soluble CD30 (sCD30) and the function of renal graft in kidney transplant recipients and investigate the immune status of recipients with combined HLA-G5 and sCD30. from January 2002 to November 2008, a total of 66 kidney transplant recipients in our centre were selected as subjects and divided into three groups: stable function of renal graft (n = 38), acute rejection (n = 15) and chronic rejection (n = 13). The expressions of serum HLA-G5 and sCD30 were detected. There were two different immune conditions with acute/chronic allograft rejection and normal renal graft in kidney transplant recipients as evaluated by combined HLA-G5 and sCD30. The sensitivity, specificity and critical value of the method were analyzed by the curve of receiver operating characteristic. the levels of HLA-G5 and sCD30 were significantly correlated with serum creatinine (r = -0.493, 0.691, both P transplantation, the sensitivity was 78.6% and the specificity 85.7% when HLA-G5 critical value 82 microg/L and sCD30 critical value 12.2 microg/L. After one year post-transplantation: the sensitivity was 92.3% and the specificity 84.6% when HLA-G5 critical value 141 microg/L and sCD30 critical value 10.3 microg/L. the immune state of recipients are evaluated by combine HLA-G5 and sCD30 which may be a simple and valid method.

Microfluidics for investigating vaso-occlusions in sickle cell disease.

Science.gov (United States)

Horton, Renita E

2017-07-01

SCD stems from amutation in the beta globin gene. Upon deoxygenation, hemoglobin polymerizes and triggers RBC remodeling. This phenomenon is central to SCD pathogenesis as individuals suffering from the disease are plagued by painful vaso-occlusive crises episodes. These episodes are the result of a combination of processes including inflammation, thrombosis, and blood cell adhesion to the vascular wall which leads to blockages within the vasculature termed vaso-occlusions. Vaso-occlusive episodes deprive tissues of oxygen and are a major contributor to SCD-related complications; unfortunately, the complex mechanisms that contribute to vaso-occlusions are not well understood. Vaso-occlusions can occur in post-capillary venules; hence, the microvasculature is a prime target for SCD therapies. Traditional in vitro systems poorly recapitulate architectural and dynamic flow properties of in vivo systems. However, microfluidic devices can capture features of the native vasculature such as cellular composition, flow, geometry, and ECM presentation. This review, although not comprehensive, highlights microfluidic approaches that aim to improve our current understanding of the pathophysiological mechanisms surrounding SCD. Microfluidic platforms can aid in identifying factors that may contribute to disease severity and can serve as suitable test beds for novel treatment strategies which may improve patient outcomes. © 2017 John Wiley & Sons Ltd.

Lectin-like oxidized low-density lipoprotein receptor (LOX-1) in sickle cell disease vasculopathy

Science.gov (United States)

Chen, Mingyi; Qiu, Hong; Lin, Xin; Nam, David; Ogbu-Nwobodo, Lucy; Archibald, Hannah; Joslin, Amelia; Wun, Ted; Sawamura, Tatsuya; Green, Ralph

2017-01-01

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is an endothelial receptor for oxidized LDL. Increased expression of LOX-1 has been demonstrated in atherosclerotic lesions and diabetic vasculopathy. In this study, we investigate the expression of LOX-1 receptor in sickle cell disease (SCD) vasculopathy. Expression of LOX-1 in brain vascular endothelium is markedly increased and LOX-1 gene expression is upregulated in cultured human brain microvascular endothelial cells by incubation with SCD erythrocytes. Also, the level of circulating soluble LOX-1 concentration is elevated in the plasma of SCD patients. Increased LOX-1 expression in endothelial cells is potentially involved in the pathogenesis of SCD vasculopathy. Soluble LOX-1 concentration in SCD may provide a novel biomarker for risk stratification of sickle cell vascular complications. PMID:27519944

Risk factors for sudden cardiac death among patients with schizophrenia.

Science.gov (United States)

Hou, Ping-Yi; Hung, Galen Chin-Lun; Jhong, Jia-Rong; Tsai, Shang-Ying; Chen, Chiao-Chicy; Kuo, Chian-Jue

2015-10-01

Patients with schizophrenia suffer from excessive premature mortality, and sudden cardiac death (SCD) is receiving growing attention as a potential cause. The present study investigated the incidence of SCD and its risk factors in a large schizophrenia cohort. We enrolled a consecutive series of 8264 patients diagnosed with schizophrenia (according to DSM-III-R and DSM-IV criteria) who were admitted to a psychiatric center in northern Taiwan from January 1, 1985 through December 31, 2008. By linking with national mortality database, 64 cases of SCD were identified. The standardized mortality ratio (SMR) for SCD was estimated. The cases were matched with controls randomly selected using risk-set sampling in a 1:2 ratio. A standardized chart review process was used to collect socio-demographic and clinical characteristics and the prescribed drugs for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of SCD at the index admission and the latest admission. The SMR for SCD was 4.5. For the clinical profiles at the index admission, physical disease (adjusted risk ratio [aRR]=2.91, Prisk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, Prisk for SCD. Consistently, aggressive behaviors (aRR=3.26, Prisk as well. Apart from cardiovascular profiles and antipsychotics, physical aggression is a crucial risk factor that deserves ongoing work for clarifying the mechanisms mediating SCD in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

The Clinical Significance of the MIF Homolog D-Dopachrome Tautomerase (MIF-2) and its Circulating Receptor (sCD74) in Burn Injury

Science.gov (United States)

Kim, Bong-Sung; Stoppe, Christian; Grieb, Gerrit; Leng, Lin; Sauler, Maor; Assis, David; Simons, David; Boecker, Arne Hendrick; Schulte, Wibke; Piecychna, Marta; Hager, Stephan; Bernhagen, Jürgen; Pallua, Norbert; Bucala, Richard

2016-01-01

Background We reported earlier that the cytokine macrophage migration inhibitory factor (MIF) is a potential biomarker in burn injury. In the present study, we investigated the clinical significance in severely burned patients of expression levels the newly discovered MIF family member D-dopachrome tautomerase (DDT or MIF-2) and their common soluble receptor CD74 (sCD74). Methods DDT and sCD74 serum levels were measured 20 severely burned patients and 20 controls. Serum levels were correlated to the abbreviated burn severity index (ABSI) and TBSA followed by receiver operating characteristic (ROC) analysis. Data were supported by gene expression dataset analysis of 31 burn patients and 28 healthy controls. Results CD74 and DDT were increased in burn patients. Furthermore, CD74 and DDT also were elevated in septic non-survivors when compared to survivors. Serum levels of DDT showed a positive correlation with the ABSI and TBSA in the early stage after burn injury, and the predictive character of DDT was strongest at 24 hrs. Serum levels of CD74 only correlated with the ABSI five days post-injury. Conclusions DDT may assist in the monitoring of clinical outcome and prediction of sepsis during the early post-burn period. sCD74 and MIF, by contrast, have limited value as an early predictor of death due to their delayed response to burn injury. PMID:27209369

The obstetric management of sickle cell disease.

Science.gov (United States)

Howard, Jo; Oteng-Ntim, Eugene

2012-02-01

Sickle cell disease (SCD) is the most common inherited disease worldwide and is associated with anaemia and intermittent severe pain. Pregnant women who are affected have increased maternal and fetal mortality and morbidity. In view of this obstetricians should have an awareness of this condition and its complications, and pregnancies in women with SCD should be managed by a multidisciplinary team with experience of high risk pregnancies. Ideally women should be seen preconceptually for optimisation of their SCD and partner screening. Antenatal care should include regular outpatient visits with regular monitoring for pre-eclampsia and of fetal growth. Blood transfusion should be used for the treatment of acute anaemia, acute chest syndrome or acute stroke but there is not sufficient evidence currently to recommend its use prophylactically. There is an increased prevalence of sickle crisis during pregnancy and patients should be monitored carefully throughout this time. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pro-Inflammatory Cytokines but Not Endotoxin-Related Parameters Associate with Disease Severity in Patients with NAFLD.

Directory of Open Access Journals (Sweden)

Johannie du Plessis

Full Text Available Intestinal dysbiosis and elevated lipopolysaccharides (LPS levels have been implicated in the development of obesity, insulin resistance and non-alcoholic steatohepatitis (NASH. In order to determine if LPS levels are elevated in patients with NASH compared to patients with non-alcoholic fatty liver (NAFL and, if elevated LPS levels correlated with histological severity of non-alcoholic fatty liver disease (NAFLD we compared LPS, markers of LPS bioactivity and pro-inflammatory cytokines/chemokines in patients undergoing bariatric surgery. At the time of surgery a liver biopsy was taken allowing the stratification into well-delineated subgroups including: No NAFL/NAFL; NASH; NASH with fibrosis and NASH cirrhotics, using the NAFLD Activity Score (NAS. Anthropometric data and plasma were collected for assessment of LPS, lipopolysaccharide binding protein (LBP, soluble CD14 (sCD14, intestinal-type fatty acid binding protein (iFABP, Toll-like receptors 2 and 4 (TLR2, 4 and a panel of cytokines/chemokines. Similar analysis was performed on plasma from a cohort of healthy controls. Our data indicate elevated levels of LPS, LBP, sCD14, iFABP and TLR2,4 in obese patients compared to healthy controls, however, these parameters remained unaltered within patients with limited liver disease (NAFL compared to NASH/NASH with fibrosis subgroups. Hierarchic cluster analysis using endotoxin-related parameters failed to discriminate between lean controls, NAFLD. While similar cluster analysis implementing inflammation-related parameters clearly distinguished lean controls, NALFD subgroups and NASH cirrhotics. In addition, LPS levels was not associated with disease severity while TNFα, IL8, and CCL3 featured a clear correlation with transaminase levels and the histological severity of NALFD. In conclusion our data indicate a stronger correlation for circulating inflammatory- rather than endotoxin-related parameters in progression of NAFLD and highlights the need

Transcranial Doppler Ultrasound in Peninsular Arab Patients With Sickle Cell Disease.

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Adekile, Adekunle; Hassan, Meaad; Asbeutah, Akram; Al-Hinai, Mohamed; Trad, Omar; Farhan, Nayef

2018-05-06

Transcranial Doppler ultrasound is used to identify patients with sickle cell disease (SCD) at risk for stroke. We performed transcranial Doppler studies in patients from 4 countries in the Arabian Peninsula (Kuwait, Oman, Iraq, and United Arab Emirates) to document the prevalence of abnormal transcranial Doppler findings. The patients were recruited from outpatient clinics and studied in a steady state. Transcranial Doppler examinations were performed with standard equipment by experienced operators. The time-averaged maximum mean velocity (TAMMV) was documented in the arteries of the circle of Willis. The hemoglobin (Hb) genotype was confirmed, and the fetal Hb level and complete blood counts were determined. There were 415 patients in the study, aged 2 to 18 years (mean ± SD, 8.6 ± 3.5 years). None of the patients had an abnormal TAMMV (ie, > 200 cm/s), whereas only 13 (3.1%), all from Iraq, had conditional values (170-200 cm/s) in the right middle cerebral artery and 7 (1.7%) in the left middle cerebral artery. There were no consistent TAMMV differences among male and female patients or in patients with different Hb genotypes (sickle cell anemia, sickle cell β 0- thalassemia, and sickle D). The use of hydroxyurea was associated with a lower TAMMV, whereas a blood transfusion history had no influence. Total hemoglobin, reticulocyte count, serum bilirubin, and fetal Hb values showed varying degrees of association with the TAMMV in the different vessels. This study has demonstrated the rarity of abnormal transcranial Doppler findings among Peninsular Arab patients with SCD. The guidelines for transcranial Doppler screening in this population need further studies and recommendations. © 2018 by the American Institute of Ultrasound in Medicine.

Multiple bone and joint disease in a sickle cell anaemia patient: a case report

Directory of Open Access Journals (Sweden)

John Ayodele Olaniyi

2012-05-01

Multidisciplinary approach was applied to her management and she was finally discharged home on a wheelchair. This case reflects not only the high susceptibility of SCD patients to infection, but also the morbidity and the attendant complications. It also highlights the need to forestall vaso-occlusive crisis (VOC which often predisposes them to developing osteomyelitis. There is a need to have a highly organized, well-equipped and highly subsidized Sickle Cell and rehabilitation Center in order to further improve the care of SCD patients.

Beam test of a dual layer silicon charge detector (SCD) for the CREAM experiment

International Nuclear Information System (INIS)

Park, N.H.; Ahn, H.S.; Ganel, O.; Han, J.H.; Jeon, J.A.; Kim, C.H.; Kim, K.C.; Lutz, L.; Lee, M.H.; Malinin, A.; Nam, S.; Park, I.H.; Park, J.H.; Seo, E.S.; Walpole, P.; Wu, J.; Yang, J.; Yoo, J.H.; Yoon, Y.S.; Zinn, S.Y.

2007-01-01

The Cosmic Ray Energetics and Mass (CREAM) balloon-borne experiment is designed for direct measurement of high-energy cosmic rays. The experimental goal is to measure single-element fluxes of all cosmic-ray nuclei from hydrogen to iron with energies up to the 'knee', or spectral index change near 10 15 eV, observed in the all-particle spectrum. The dual layer Silicon Charge Detector (SCD) was designed to provide precise charge measurements. Each SCD layer has an active area of 77.9cmx79.5cm and consists of 156 silicon sensors mounted on 24 ladders. Each sensor contains a 4 x 4 array of single-sided DC type silicon pixels with an active area of 2.1cm 2 . The detector was flown on the second CREAM flight (December 2005-January 2006) and recovered successfully. The SCD was refurbished for the third CREAM flight and tested with high-energy electron and hadron beams at CERN. This paper reports on the performance of the SCD during the beam test

Adherence to hydroxyurea, health-related quality of life domains, and patients' perceptions of sickle cell disease and hydroxyurea: a cross-sectional study in adolescents and young adults.

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Badawy, Sherif M; Thompson, Alexis A; Lai, Jin-Shei; Penedo, Frank J; Rychlik, Karen; Liem, Robert I

2017-07-05

Sickle cell disease (SCD) patients have impaired domains of health-related quality of life (HRQOL). Hydroxyurea is safe and efficacious in SCD; however, adherence is suboptimal, and patients' perceptions are poorly understood amongst adolescents and young adults (AYA). Study objectives were to: (1) examine patients' perceptions of SCD and hydroxyurea; and (2) explore the relationship of their perceptions to clinical characteristics, HRQOL domains and hydroxyurea adherence. Thirty-four SCD patients on hydroxyurea (≥6 months) participated in a single-institution study. Study measures included Brief-Illness Perceptions Questionnaire, ©Modified Morisky Adherence Scale 8-items, and Patient Reported Outcomes Measurement Information System (PROMIS®). We assessed the relationship of patients' perceptions to hydroxyurea adherence using Wilcoxon rank-sum test, the number of hospitalizations using Kruskal-Wallis test, and the number of ED visits, adherence level, HRQOL domain scores using Spearman's rho correlations. We conducted a sub-analysis in HbSS patients to evaluate the relationship of patients' perceptions to laboratory markers of hydroxyurea adherence. Participants were 59% male and 91% Black, and had a median age of 13.5 (range 12-18) years. Participants with ≥4 hospitalizations over 1-year prior (using electronic medical chart review) reported more negative perceptions of SCD-related symptoms and emotional response, and perceived hydroxyurea as less beneficial; all p-values ≤0.01. Most participants (74%) reported low hydroxyurea adherence. Participants with higher hydroxyurea adherence perceived more hydroxyurea benefits (r s  = 0.44, p hydroxyurea positively correlated with HbF (r s  = 0.37, p = 0.05) and MCV values (r s  = 0.35, p = 0.05). Participants with more negative perceptions of SCD-related consequences, concerns, and emotional response, and fewer perceived hydroxyurea benefits reported worse fatigue (r s  = 0.68; r s  = 0.44; r s �

Development, Content Validity, and User Review of a Web-based Multidimensional Pain Diary for Adolescent and Young Adults With Sickle Cell Disease.

Science.gov (United States)

Bakshi, Nitya; Stinson, Jennifer N; Ross, Diana; Lukombo, Ines; Mittal, Nonita; Joshi, Saumya V; Belfer, Inna; Krishnamurti, Lakshmanan

2015-06-01

Vaso-occlusive pain, the hallmark of sickle cell disease (SCD), is a major contributor to morbidity, poor health-related quality of life, and health care utilization associated with this disease. There is wide variation in the burden, frequency, and severity of pain experienced by patients with SCD. As compared with health care utilization for pain, a daily pain diary captures the breadth of the pain experience and is a superior measure of pain burden and its impact on patients. Electronic pain diaries based on real-time data capture methods overcome methodological barriers and limitations of paper pain diaries, but their psychometric properties have not been formally established in patients with SCD. To develop and establish the content validity of a web-based multidimensional pain diary for adolescents and young adults with SCD and conduct an end-user review to refine the prototype. Following identification of items, a conceptual model was developed. Interviews with adolescents and young adults with SCD were conducted. Subsequently, end-user review with use of the electronic pain diary prototype was conducted. Two iterative cycles of in-depth cognitive interviews in adolescents and young adults with SCD informed the design and guided the addition, removal, and modification of items in the multidimensional pain diary. Potential end-users provided positive feedback on the design and prototype of the electronic diary. A multidimensional web-based electronic pain diary for adolescents and young adults with SCD has been developed and content validity and initial end-user reviews have been completed.

Long-term safety and efficacy of deferasirox (Exjade) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease.

Science.gov (United States)

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-08-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥ 4 years deferasirox exposure significantly decreased by -591 μg/l (95% confidence intervals, -1411, -280 μg/l; P = 0·027; n = 67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. © 2011 Blackwell Publishing Ltd.

Granulomas at initial diagnosis of Crohn's disease signal a poor ...

African Journals Online (AJOL)

CD patients (n=101) with uncomplicated non-stricturing, non-penetrating disease at diagnosis, and with follow-up >5 years, were retrospectively analysed using a predefined definition of severe CD (SCD) over the disease course. Clinical, demographic, laboratory and histological factors at diagnosis associated with SCD ...

Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

Directory of Open Access Journals (Sweden)

Laura Breda

Full Text Available Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+ cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A and concurrently reducing the sickling tetramer (Hb S.Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these

Is there an added value of faecal calprotectin and haemoglobin in the diagnostic work-up for primary care patients suspected of significant colorectal disease? A cross-sectional diagnostic study

NARCIS (Netherlands)

Elias, Sjoerd G.; Kok, Liselotte; de Wit, NJ; Witteman, Ben J. M.; Goedhard, Jelle G.; Romberg-Camps, Marielle J. L.; Muris, Jean W. M.; Moons, Karel G. M.

2016-01-01

Background The majority of primary care patients referred for bowel endoscopy do not have significant colorectal disease (SCD), and are – in hindsight – unnecessarily exposed to a small but realistic risk of severe endoscopy-associated complications. We developed a diagnostic strategy to better

Self-Reported Physical Activity and Exercise Patterns in Children With Sickle Cell Disease.

Science.gov (United States)

Omwanghe, Osarhiemen A; Muntz, Devin S; Kwon, Soyang; Montgomery, Simone; Kemiki, Opeyemi; Hsu, Lewis L; Thompson, Alexis A; Liem, Robert I

2017-08-01

Sickle cell disease (SCD) significantly affects physical functioning. We examined physical activity (PA) patterns in children with SCD versus a national sample and factors associated with PA and participation in physical education and organized sports. One hundred children with SCD completed a 58-item survey with questions from the 2009-2010 National Health and Nutrition Examination Survey (NHANES) Physical Activity Questionnaire and others on physical education and sports, disease impact, and physical functioning. Compared with NHANES participants, more children with SCD (67 vs 42%, p physical education and sports, respectively. Greater disease impact on PA and physical functioning were associated with lower participation. Children with SCD are active at moderate to vigorous intensity for shorter durations. Negative personal beliefs about disease impact and poor physical functioning represent barriers to PA in SCD.

Comprehensive analysis of sperm DNA fragmentation by five different assays: TUNEL assay, SCSA, SCD test and alkaline and neutral Comet assay.

Science.gov (United States)

Ribas-Maynou, J; García-Peiró, A; Fernández-Encinas, A; Abad, C; Amengual, M J; Prada, E; Navarro, J; Benet, J

2013-09-01

Sperm DNA fragmentation (SDF) is becoming an important test to assess male infertility. Several different tests are available, but no consensus has yet been reached as to which tests are most predictive of infertility. Few publications have reported a comprehensive analysis comparing these methods within the same population. The objective of this study was to analyze the differences between the five most common methodologies, to study their correlations and to establish their cut-off values, sensitivity and specificity in predicting male infertility. We found differences in SDF between fertile donors and infertile patients in TUNEL, SCSA, SCD and alkaline Comet assays, but none with the neutral Comet assay. The alkaline COMET assay was the best in predicting male infertility followed by TUNEL, SCD and SCSA, whereas the neutral COMET assay had no predictive power. For our patient population, threshold values for infertility were 20.05% for TUNEL assay, 18.90% for SCSA, 22.75% for the SCD test, 45.37% for alkaline Comet and 34.37% for neutral Comet. This work establishes in a comprehensive study that the all techniques except neutral Comet are useful to distinguish fertile and infertile men. © 2013 American Society of Andrology and European Academy of Andrology.

Using Quality Improvement Methods to Implement an Electronic Medical Record (EMR) Supported Individualized Home Pain Management Plan for Children with Sickle Cell Disease.

Science.gov (United States)

Crosby, Lori E; Simmons, Kenya; Kaiser, Peggy; Davis, Blair; Boyd, Patricia; Eichhorn, Tiffany; Mahaney, Tracy; Joffe, Naomi; Morgan, Darice; Schibler, Kathy; Anderson, Viia; Quinn, Charles T; Kalinyak, Karen A

2014-05-01

Using quality improvement methodology, our goal was to develop and implement individualized home pain management plans (HPMP) that included pharmacologic as well as non-pharmacologic strategies for children with sickle cell disease (SCD). We hypothesized that successfully implemented HPMPs would have an impact on Emergency Department (ED) use, decreasing ED visits for uncomplicated SCD pain episodes. A multidisciplinary quality improvement team developed a questionnaire to assess the frequency, location and severity of a patient's pain during a routine, comprehensive visit in order to help the patient and family develop an effective pain management strategy using both pharmacologic and non-pharmacologic actions. Using plan do study act cycles (PDSAs), this team was able to build this process into the daily workflow for all SCD patients age 5 years to 21 years of age. Patients with comprehensive visits scheduled from January 2012 to May 2013 were included (N=188) in the intervention. By May of 2013, 88% of eligible patients had an individualized HPMP in place. There was a concomitant reduction in the percentage of SCD patients seen in the ED for uncomplicated SCD pain (6.9% vs. 1.1%). Using quality improvement methods, an individualized HPMP intervention was incorporated successfully into the daily workflow of a busy outpatient SCD clinic. This intervention has the potential to improve patient outcomes by decreasing avoidable ED visits as well as reducing overall healthcare costs.

Sickle cell disease pain management in adolescents: a literature review.

Science.gov (United States)

Wilson, Bridget H; Nelson, Jessica

2015-04-01

Sickle cell disease (SCD) pain continues to emerge in adolescents. More than 98,000 individuals are believed to have SCD in the United States. In fact, 1 in 500 Black infants will be affected by SCD. Identifying standards of care for this unique population can improve pain management and treatment. A significant effect of vaso-occlusive crisis is a decrease in the quality of life in children. Therefore, pain management is multidimensional and includes pharmacologic, physical, and psychological strategies. A review of the literature was conducted to identify best practices regarding pain management in adolescents with sickle cell anemia. Key words such as pain, pain management, adolescent sickle cell anemia, and acute sickle cell pain were entered into databases to reveal qualitative and quantitative studies from 2009 to the present. Many of the research articles identified poor SCD pain management. Studies showed that acute SCD pain management is essential and should be evaluated and robustly managed to achieve optimum pain relief for patients. Acute SCD pain usually occurs as a result of vaso-occlusive crisis. Untreated acute SCD pain can result in morbidity and mortality in adolescents. Nursing knowledge is critical to reducing the stigma and improving management of SCD pain. Nurses play a vital role in the introduction of evidence-based practice within the clinical setting. In an effort to educate nurses and other health care professionals about SCD, this article is a literature review of studies concerning SCD and pain management in emergency rooms. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

A Mismatch Between Patient Education Materials About Sickle Cell Disease and the Literacy Level of Their Intended Audience.

Science.gov (United States)

McClure, Elizabeth; Ng, Jared; Vitzthum, Kelly; Rudd, Rima

2016-05-12

Despite the first goal of the 2010 National Action Plan to Improve Health Literacy, the literacy demands of much health information exceeds the reading skills of most US adults. The objective of this study was to assess the health literacy level of publicly available patient education materials for people with sickle cell disease (SCD). We used 5 validated tools to evaluate 9 print and 4 online patient education materials: the simple measure of gobbledygook (SMOG) to assess reading grade level, the Peter Mosenthal and Irwin Kirsch readability formula (PMOSE/IKIRSCH) to assess structure and density, the Patient Education Materials Assessment Tool (PEMAT) to assess actionability (how well readers will know what to do after reading the material) and understandability, the Centers for Disease Control and Prevention's (CDC's) Clear Communication Index (Index) to obtain a comprehensive literacy demand score, and the Printed Cancer Education Materials for African Americans Cultural Sensitivity Assessment Tool. Materials' scores reflected high reading levels ranging from 8th grade to 12th grade, appropriate (low) structural demand, and low actionability relative to understandability. CDC suggests that an appropriate Index score should fall in or above the 90th percentile. The scores yielded by materials evaluated in this assessment ranged from the 44th to the 76th percentiles. Eight of the 13 materials scored within the acceptable range for cultural sensitivity. Reading levels of available patient education materials exceed the documented average literacy level of the US adult population. Health literacy demands should be a key consideration in the revision and development of patient education materials for people with SCD.

Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication.

Science.gov (United States)

Quinn, Charles T

2016-04-01

Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges. © 2016 by the Society for Experimental Biology and Medicine.

Long-term safety and efficacy of deferasirox (Exjade®) for up to 5 years in transfusional iron-overloaded patients with sickle cell disease

Science.gov (United States)

Vichinsky, Elliott; Bernaudin, Françoise; Forni, Gian Luca; Gardner, Renee; Hassell, Kathryn; Heeney, Matthew M; Inusa, Baba; Kutlar, Abdullah; Lane, Peter; Mathias, Liesl; Porter, John; Tebbi, Cameron; Wilson, Felicia; Griffel, Louis; Deng, Wei; Giannone, Vanessa; Coates, Thomas

2011-01-01

To date, there is a lack of long-term safety and efficacy data for iron chelation therapy in transfusion-dependent patients with sickle cell disease (SCD). To evaluate the long-term safety and efficacy of deferasirox (a once-daily oral iron chelator), patients with SCD completing a 1-year, Phase II, randomized, deferoxamine (DFO)-controlled study entered a 4-year extension, continuing to receive deferasirox, or switching from DFO to deferasirox. Average actual deferasirox dose was 19·4 ± 6·3 mg/kg per d. Of 185 patients who received at least one deferasirox dose, 33·5% completed the 5-year study. The most common reasons for discontinuation were withdrawal of consent (23·8%), lost to follow-up (9·2%) and adverse events (AEs) (7·6%). Investigator-assessed drug-related AEs were predominantly gastrointestinal [including nausea (14·6%), diarrhoea (10·8%)], mild-to-moderate and transient in nature. Creatinine clearance remained within the normal range throughout the study. Despite conservative initial dosing, serum ferritin levels in patients with ≥4 years deferasirox exposure significantly decreased by −591 μg/l (95% confidence intervals, −1411, −280 μg/l; P=0·027; n=67). Long-term deferasirox treatment for up to 5 years had a clinically acceptable safety profile, including maintenance of normal renal function, in patients with SCD. Iron burden was substantially reduced with appropriate dosing in patients treated for at least 4 years. PMID:21592110

[Chronic renal failure in sickle cell disease: A retrospective analysis of 100 adults sickle cell patients from black Africa].

Science.gov (United States)

Ackoundou-N'Guessan, Clément; Guei, Cyr Monley; Lagou, Delphine Amélie; Gbekedi, Serges; Tia, Mélanie Weu; Coulibaly, Pessa Albert; Nzoue, Sita; Konan, Serges; Koffi, Gustave; Gnionsahe, Daze Apollinaire

2016-06-01

The prevalence of chronic renal failure (CRF) in sickle cell disease (SCD) patients could vary from one country to another depending on the modalities of management. The aim of the present study was to appreciate the epidemiology of CRF in SCD patients from black Africa in order to search for promoting factors. One hundred SCD adult patients have been considered for the study. The glomerular filtration rate (GFR) has been estimated according to the CKD-EPI formula. Three groups of patients have been identified according to the value of their GFR. The mean age of the patients was 30.84±8.26 years. Male gender has represented 51% of the study population. The mean GFR value was 175.4±86.2 mL/min/1.73 m(2). The prevalence of CRF was 11%. About 3% of them had severe CRF. Subjects with normal GFR were 20%. Subjects with glomerular hyperfiltration (HF) were 69%. By univariate analysis, when subjects with HF were compared with those presenting normal GFR, the following factors have appeared to be significantly associated: female gender (female 60.9% versus male 39.1%; P60 kg; 59.9±9.41 kg; P30 years; OR=0.12 [CI95% 0.03-04]; P60 kg; OR=0.19 [CI95% 0.05-0.72]; P<0.01) were associated with HF. By univariate analysis, when subjects with CRF were compared with those presenting normal GFR, a lower hemoglobin value was significantly associated with CRF (7.92±2.7 g/dL versus 10.43±2.5 g/dL; P<0.009). There was a trend for subjects not being under maintenance therapy to more experience CRF (36.4% versus 70%; P<0.07). By logistic regression analysis, only a low hemoglobin value was associated to CRF (higher hemoglobin level; OR=0.55 [0.20-6.3]; P<0.01). In total, CRF and HF are frequent complications in SCD adult patients from black Africa. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

sCD30, interleukin-1beta-converting enzyme and anti-Annexin V autoantibodies concentrations in heart transplant recipients.

Science.gov (United States)

Zeglen, Sławomir; Zakliczyński, Michał; Nozyński, Jerzy; Rogala, Barbara; Zembala, Marian

2006-11-01

sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker--anti-Annexin V antibodies and myocardial biopsies results. 28 clinically stabile patients--heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age=36.8 years, S.D.=7.6) with normal heart function assessed by use of ultrasound scan--were involved in the trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1beta-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used. sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups--with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (-0.65, psCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.

Large and medium-sized pulmonary artery obstruction does not play a role of primary importance in the etiology of sickle-cell disease-associated pulmonary hypertension

NARCIS (Netherlands)

van Beers, Eduard J.; van Eck-Smit, Berthe L. F.; Mac Gillavry, Melvin R.; van Tuijn, Charlotte F. J.; van Esser, Joost W. J.; Brandjes, Dees P. M.; Kappers-Klunne, Mies C.; Duits, Ashley J.; Biemond, Bart J.; Schnog, John-John B.

2008-01-01

Background: Pulmonary hypertension (PHT) occurs in approximately 30% of adult patients with sickle-cell disease (SCD) and is a risk factor for early death. The potential role of pulmonary artery obstruction, whether due to emboli or in situ thrombosis, in the etiology of SCD-related PHT is unknown.

Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity

DEFF Research Database (Denmark)

Heftdal, Line Dam; Stengaard-Pedersen, Kristian; Ørnbjerg, Lykke Midtbøll

2017-01-01

internalization and degradation. The soluble form has been suggested as a biomarker of M2A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients...... from baseline after 6 months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved......Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2A-macrophages and dendritic cells. It is involved in collagen...

Development and Production of Array Barrier Detectors at SCD

Science.gov (United States)

Klipstein, P. C.; Avnon, E.; Benny, Y.; Berkowicz, E.; Cohen, Y.; Dobromislin, R.; Fraenkel, R.; Gershon, G.; Glozman, A.; Hojman, E.; Ilan, E.; Karni, Y.; Klin, O.; Kodriano, Y.; Krasovitsky, L.; Langof, L.; Lukomsky, I.; Nevo, I.; Nitzani, M.; Pivnik, I.; Rappaport, N.; Rosenberg, O.; Shtrichman, I.; Shkedy, L.; Snapi, N.; Talmor, R.; Tessler, R.; Weiss, E.; Tuito, A.

2017-09-01

XB n or XB p barrier detectors exhibit diffusion-limited dark currents comparable with mercury cadmium telluride Rule-07 and high quantum efficiencies. In 2011, SemiConductor Devices (SCD) introduced "HOT Pelican D", a 640 × 512/15- μm pitch InAsSb/AlSbAs XB n mid-wave infrared (MWIR) detector with a 4.2- μm cut-off and an operating temperature of ˜150 K. Its low power (˜3 W), high pixel operability (>99.5%) and long mean time to failure make HOT Pelican D a highly reliable integrated detector-cooler product with a low size, weight and power. More recently, "HOT Hercules" was launched with a 1280 × 1024/15- μm format and similar advantages. A 3-megapixel, 10- μm pitch version ("HOT Blackbird") is currently completing development. For long-wave infrared applications, SCD's 640 × 512/15- μm pitch "Pelican-D LW" XB p type II superlattice (T2SL) detector has a ˜9.3- μm cut-off wavelength. The detector contains InAs/GaSb and InAs/AlSb T2SLs, and is fabricated into focal plane array (FPA) detectors using standard production processes including hybridization to a digital silicon read-out integrated circuit (ROIC), glue underfill and substrate thinning. The ROIC has been designed so that the complete detector closely follows the interfaces of SCD's MWIR Pelican-D detector family. The Pelican-D LW FPA has a quantum efficiency of ˜50%, and operates at 77 K with a pixel operability of >99% and noise equivalent temperature difference of 13 mK at 30 Hz and F/2.7.

the orthodontic management of an adult with sickle cell disease

African Journals Online (AJOL)

2015-09-01

Sep 1, 2015 ... a patient with Sickle Cell Disease (SCD) needs ortho- dontic treatment ... Orthodontic Management. 215. Measures ... under strict control by the Dental Hygienists to avoid ... Ghana. Pediatrics 2008; 121 (suppl 2): 120-121. 2.

Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59.

Science.gov (United States)

Zelek, Wioleta M; Watkins, Lewis M; Howell, Owain W; Evans, Rhian; Loveless, Sam; Robertson, Neil P; Beenes, Marijke; Willems, Loek; Brandwijk, Ricardo; Morgan, B Paul

2018-02-01

CD59, a broadly expressed glycosylphosphatidylinositol-anchored protein, is the principal cell inhibitor of complement membrane attack on cells. In the demyelinating disorders, multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), elevated complement protein levels, including soluble CD59 (sCD59), were reported in cerebrospinal fluid (CSF). We compared sCD59 levels in CSF and matched plasma in controls and patients with MS, NMOSD and clinically isolated syndrome (CIS) and investigated the source of CSF sCD59 and whether it was microparticle associated. sCD59 was quantified using enzyme-linked immunosorbent assay (ELISA; Hycult; HK374-02). Patient and control CSF was subjected to western blotting to characterise anti-CD59-reactive materials. CD59 was localised by immunostaining and in situ hybridisation. CSF sCD59 levels were double those in plasma (CSF, 30.2 ng/mL; plasma, 16.3 ng/mL). Plasma but not CSF sCD59 levels differentiated MS from NMOSD, MS from CIS and NMOSD/CIS from controls. Elimination of microparticles confirmed that CSF sCD59 was not membrane anchored. CSF levels of sCD59 are not a biomarker of demyelinating diseases. High levels of sCD59 in CSF relative to plasma suggest an intrathecal source; CD59 expression in brain parenchyma was low, but expression was strong on choroid plexus (CP) epithelium, immediately adjacent the CSF, suggesting that this is the likely source.

Exploring APOE genotype effects on Alzheimer's disease risk and amyloid β burden in individuals with subjective cognitive decline: The FundacioACE Healthy Brain Initiative (FACEHBI) study baseline results.

Science.gov (United States)

Moreno-Grau, Sonia; Rodríguez-Gómez, Octavio; Sanabria, Ángela; Pérez-Cordón, Alba; Sánchez-Ruiz, Domingo; Abdelnour, Carla; Valero, Sergi; Hernández, Isabel; Rosende-Roca, Maitée; Mauleón, Ana; Vargas, Liliana; Lafuente, Asunción; Gil, Silvia; Santos-Santos, Miguel Ángel; Alegret, Montserrat; Espinosa, Ana; Ortega, Gemma; Guitart, Marina; Gailhajanet, Anna; de Rojas, Itziar; Sotolongo-Grau, Óscar; Ruiz, Susana; Aguilera, Nuria; Papasey, Judith; Martín, Elvira; Peleja, Esther; Lomeña, Francisco; Campos, Francisco; Vivas, Assumpta; Gómez-Chiari, Marta; Tejero, Miguel Ángel; Giménez, Joan; Serrano-Ríos, Manuel; Orellana, Adelina; Tárraga, Lluís; Ruiz, Agustín; Boada, Mercè

2018-05-01

Subjective cognitive decline (SCD) has been proposed as a potential preclinical stage of Alzheimer's disease (AD). Nevertheless, the genetic and biomarker profiles of SCD individuals remain mostly unexplored. We evaluated apolipoprotein E (APOE) ε4's effect in the risk of presenting SCD, using the Fundacio ACE Healthy Brain Initiative (FACEHBI) SCD cohort and Spanish controls, and performed a meta-analysis addressing the same question. We assessed the relationship between APOE dosage and brain amyloid burden in the FACEHBI SCD and Alzheimer's Disease Neuroimaging Initiative cohorts. Analysis of the FACEHBI cohort and the meta-analysis demonstrated SCD individuals presented higher allelic frequencies of APOE ε4 with respect to controls. APOE dosage explained 9% (FACEHBI cohort) and 11% (FACEHBI and Alzheimer's Disease Neuroimaging Initiative cohorts) of the variance of cerebral amyloid levels. The FACEHBI sample presents APOE ε4 enrichment, suggesting that a pool of AD patients is nested in our sample. Cerebral amyloid levels are partially explained by the APOE allele dosage, suggesting that other genetic or epigenetic factors are involved in this AD endophenotype. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Newborn blood spot screening for sickle cell disease by using tandem mass spectrometry: implementation of a protocol to identify only the disease states of sickle cell disease.

Science.gov (United States)

Moat, Stuart J; Rees, Derek; King, Lawrence; Ifederu, Adeboye; Harvey, Katie; Hall, Kate; Lloyd, Geoff; Morrell, Christine; Hillier, Sharon

2014-02-01

The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, D(Punjab), O(Arab), Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

Alignment of single-case design (SCD) research with individuals who are deaf or hard of hearing with the what Works Clearinghouse standards for SCD research.

Science.gov (United States)

Wendel, Erica; Cawthon, Stephanie W; Ge, Jin Jin; Beretvas, S Natasha

2015-04-01

The authors assessed the quality of single-case design (SCD) studies that assess the impact of interventions on outcomes for individuals who are deaf or hard-of-hearing (DHH). More specifically, the What Works Clearinghouse (WWC) standards for SCD research were used to assess design quality and the strength of evidence of peer-reviewed studies available in the peer-reviewed, published literature. The analysis yielded four studies that met the WWC standards for design quality, of which two demonstrated moderate to strong evidence for efficacy of the studied intervention. Results of this review are discussed in light of the benefits and the challenges to applying the WWC design standards to research with DHH individuals and other diverse, low-incidence populations. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cranial epidural hematomas: A case series and literature review of this rare complication associated with sickle cell disease.

Science.gov (United States)

Hamm, Jennifer; Rathore, Nisha; Lee, Pearlene; LeBlanc, Zachary; Lebensburger, Jeffrey; Meier, Emily Riehm; Kwiatkowski, Janet L

2017-03-01

Patients with sickle cell disease (SCD) may experience many complications of the central nervous system (CNS) including stroke, silent cerebral infarcts, and neuropsychological deficits. Cranial epidural hematoma is a rare but potentially serious complication. Case series of cranial epidural hematomas in children with SCD from three different institutions is considered, along with a literature review of cranial epidural hematomas in this population. Seven children with SCD with cranial epidural hematomas were identified from three different institutions. All patients were male and the age at presentation ranged from 10 to 18 years. Two patients presented with headache (28.6%), while the rest had no neurologic symptoms at presentation. Four patients required urgent neurosurgical intervention (57.1%) and one patient died (14.3%). A literature review identified 18 additional cases of cranial epidural hematomas in children with SCD. Of these, treatment ranged from supportive care to neurosurgical intervention. Twelve patients completely recovered (66.7%), one patient had long-term cognitive impairment (5.6%), and four patients died (22.2%). Combined with our data, cranial epidural hematomas have a mortality rate of 20.0%. Although rare, cranial epidural hematoma can be fatal and should be considered in patients with acute neurological symptoms. © 2016 Wiley Periodicals, Inc.

Detrimental effects of adenosine signaling in sickle cell disease

Science.gov (United States)

Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

2016-01-01

Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A2B receptor (A2BR)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A2BR has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease. PMID:21170046

Effects of vaccines in patients with sickle cell disease: a systematic review protocol.

Science.gov (United States)

Wiyeh, Alison Beriliy; Abdullahi, Leila Hussein; Wonkam, Ambroise; Wiysonge, Charles Shey; Kaba, Mamadou

2018-03-25

Sickle cell disease (SCD) is an inherited haematological disorder caused by a single point mutation (Glub6Val) that promotes polymerisation of haemoglobin S and sickling of erythrocytes. Inflammation, haemolysis, microvascular obstruction and organ damage characterise the highly variable clinical expression of SCD. People with SCD are at increased risk of severe infections, hence the need for vaccination against common disease-causing organisms in this population. We aim to review the evidence on the efficacy and safety of vaccines in people with SCD. The present systematic review will examine the current data as indexed in PubMed, CENTRAL, EMBASE and EBSCOHost. We will consult Strategic Advisory Group of Experts practice statements, conference abstracts, reference lists of relevant articles, WHO ICTRP trial registry and experts in the field. Two authors will independently screen search outputs, select studies, extract data and assess risk of bias; resolving discrepancies by discussion and consensus between the two authors or arbitration by a third author when necessary. We will perform a meta-analysis for clinically homogenous studies. Evidence from clinically diverse studies will be aggregated using narrative synthesis of the findings. In either case, we will use the GRADE approach to assess the strength of the available evidence. The study draws on data that are readily available in the public domain, hence no formal ethical review and approval is required. The findings of this review will be disseminated through conference presentations and a publication in a peer-reviewed journal. CRD42018084051. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Malevolent ogbanje: recurrent reincarnation or sickle cell disease?

Science.gov (United States)

Nzewi, E

2001-05-01

The Igbo of Nigeria believe that everyone is ogbanje (reincarnates) but malevolent ogbanje differ from others in being revenge-driven, chronically ill and engaging in repeated cycles of birth, death and reincarnation. This study examined culturally defined symptoms of 100 children classified as malevolent ogbanje; and investigated their family history and child mortality experience. There was concordance between cultural descriptions of malevolent ogbanje and symptoms as manifested in sickle cell patients. Hemoglobin analysis showed that 70 of the 100 children had sickle cell disease (SCD); while 68 families had death-related names. The symptoms associated with Igbo cases of reincarnation, high child mortality rates, and the high prevalence of sickle cell disease among children classified as malevolent ogbanje all support the conclusion that the symptomatology and early mortality experience are related to sickle cell. Names with themes of death were prevalent in families of children described as malevolent ogbanje. The findings are discussed with reference to cultural resistance to SCD as an explanation for malevolent ogbanje and the implications for the health care of children with SCD in Nigeria.

Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

Science.gov (United States)

Ameen, Reem; Al Shemmari, Salem; Al-Bashir, Abdulaziz

2009-08-01

Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

Are Patients with Spontaneous CSF Otorrhea and Superior Canal Dehiscence Congenitally Predisposed to Their Disorders?

Science.gov (United States)

Stevens, Shawn M; Hock, Kiefer; Samy, Ravi N; Pensak, Myles L

2018-04-01

Objectives (1) Compare lateral skull base (LSB) height/thickness in patients with spontaneous cerebrospinal fluid otorrhea (CSF), superior canal dehiscence (SCD), acoustic neuromas (AN), and otosclerosis (OTO). (2) Perform correlations between age, body mass index (BMI), sex, and LSB height/thickness. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods Patients with CSF, SCD, AN, and OTO diagnosed from 2006 to 2016 were included if they had high-definition temporal bone computed tomography (CT) and absence of trauma, radiation, chronic ear disease, and/or congenital anomaly. CT-based measurements included LSB height/thickness and pneumatization rates overlaying the external auditory canal (EAC), tegmen tympani (TgT), perigeniculate region (PG), and internal auditory canal (IAC). LSB height/thickness, age, sex, and BMI were statistically correlated. In total, 256 patients and 493 ears (109 CSF, 115 SCD, 269 AN/OTO) were measured. Results Patients with CSF had significantly higher BMIs than the other groups ( P CSF and SCD had similar radiographic LSB phenotypes at most measured locations. Both groups exhibited a significantly lower LSB height compared to the AN and OTO groups (mean, 3.9-4.2 mm vs 4.9-5.6 mm; P CSF and SCD also demonstrated significantly lower pneumatization rates, as low as 17% to 23% overlaying the PG and IAC ( P CSF and SCD exhibit similar radiographic LSB phenotypes. Age, sex, and BMI do not significantly correlate with LSB height/thickness. These data support the theory that CSF and SCD arise via similar congenital pathoetiologic mechanisms.

Saccharomyces cerevisiae-derived virus-like particle parvovirus B19 vaccine elicits binding and neutralizing antibodies in a mouse model for sickle cell disease.

Science.gov (United States)

Penkert, Rhiannon R; Young, Neal S; Surman, Sherri L; Sealy, Robert E; Rosch, Jason; Dormitzer, Philip R; Settembre, Ethan C; Chandramouli, Sumana; Wong, Susan; Hankins, Jane S; Hurwitz, Julia L

2017-06-22

Parvovirus B19 infections are typically mild in healthy individuals, but can be life threatening in individuals with sickle cell disease (SCD). A Saccharomyces cerevisiae-derived B19 VLP vaccine, now in pre-clinical development, is immunogenic in wild type mice when administered with the adjuvant MF59. Because SCD alters the immune response, we evaluated the efficacy of this vaccine in a mouse model for SCD. Vaccinated mice with SCD demonstrated similar binding and neutralizing antibody responses to those of heterozygous littermate controls following a prime-boost-boost regimen. Due to the lack of a mouse parvovirus B19 challenge model, we employed a natural mouse pathogen, Sendai virus, to evaluate SCD respiratory tract responses to infection. Normal mucosal and systemic antibody responses were observed in these mice. Results demonstrate that mice with SCD can respond to a VLP vaccine and to a respiratory virus challenge, encouraging rapid development of the B19 vaccine for patients with SCD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Red blood cell alloimmunization in sickle cell disease patients in ...

African Journals Online (AJOL)

Objective: Alloimmunization is a recognized complication of red blood cell (RBC) transfusion and causes delayed hemolytic transfusion reactions and provides problems sourcing compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in ...

Asymptomatic bacteriuria in sickle cell disease: a cross-sectional study

Directory of Open Access Journals (Sweden)

Roye-Green Karen

2006-03-01

Full Text Available Background It is known that there is significant morbidity associated with urinary tract infection and with renal dysfunction in sickle cell disease (SCD. However, it is not known if there are potential adverse outcomes associated with asymptomatic bacteriuria (ASB infections in sickle cell disease if left untreated. This study was undertaken to determine the prevalence of ASB, in a cohort of patients with SCD. Methods This is a cross-sectional study of patients in the Jamaican Sickle Cell Cohort. Aseptically collected mid-stream urine (MSU samples were obtained from 266 patients for urinalysis, culture and sensitivity analysis. Proteinuria was measured by urine dipsticks. Individuals with abnormal urine culture results had repeat urine culture. Serum creatinine was measured and steady state haematology and uric acid concentrations were obtained from clinical records. This was completed at a primary care health clinic dedicated to sickle cell diseases in Kingston, Jamaica. There were 133 males and 133 females in the sample studied. The mean age (mean ± sd of participants was 26.6 ± 2.5 years. The main outcome measures were the culture of ≥ 105 colony forming units of a urinary tract pathogen per milliliter of urine from a MSU specimen on a single occasion (probable ASB or on consecutive occasions (confirmed ASB. Results Of the 266 urines collected, 234 were sterile and 29 had significant bacteriuria yielding a prevalence of probable ASB of 10.9% (29/266. Fourteen patients had confirmed ASB (prevalence 5.3% of which 13 had pyuria. Controlling for genotype, females were 14.7 times more likely to have confirmed ASB compared to males (95%CI 1.8 to 121.0. The number of recorded visits for symptomatic UTI was increased by a factor of 2.5 (95% CI 1.4 to 4.5, p Conclusion ASB is a significant problem in individuals with SCD and may be the source of pathogens in UTI. However, further research is needed to determine the clinical significance of ASB in

Sickle Cell Disease: New Opportunities and Challenges in Africa

Directory of Open Access Journals (Sweden)

J. Makani

2013-01-01

Full Text Available Sickle cell disease (SCD is one of the most common genetic causes of illness and death in the world. This is a review of SCD in Africa, which bears the highest burden of disease. The first section provides an introduction to the molecular basis of SCD and the pathophysiological mechanism of selected clinical events. The second section discusses the epidemiology of the disease (prevalence, morbidity, and mortality, at global level and within Africa. The third section discusses the laboratory diagnosis and management of SCD, emphasizing strategies that been have proven to be effective in areas with limited resources. Throughout the review, specific activities that require evidence to guide healthcare in Africa, as well as strategic areas for further research, will be highlighted.

[Infectious complications after surgical splenectomy in children with sickle cell anemia disease].

Science.gov (United States)

Monaco Junior, Cypriano Petrus; Fonseca, Patricia Belintani Blum; Braga, Josefina Aparecida Pellegrini

2015-01-01

To evaluate the frequency of infectious complications in children with sickle cell disease (SCD) after surgical splenectomy for acute splenic sequestration crisis. Retrospective cohort of children with SCD who were born after 2002 and were regularly monitored until July 2013. Patients were divided into two groups: cases (children with SCD who underwent surgical splenectomy after an episode of splenic sequestration) and controls (children with SCD who did not have splenic sequestration and surgical procedures), in order to compare the frequency of invasive infections (sepsis, meningitis, bacteremia with positive blood cultures, acute chest syndrome and/or pneumonia) by data collected from medical records. Data were analyzed by descriptive statistical analysis. 44 patients were included in the case group. The mean age at the time of splenectomy was 2.6 years (1-6.9 years) and the mean postoperative length of follow-up was 6.1 years (3.8-9.9 years). The control group consisted of 69 patients with a mean age at the initial follow-up visit of 5.6 months (1-49 months) and a mean length of follow-up of 7.2 years (4-10.3 years). All children received pneumococcal conjugate vaccine. No significant difference was observed between groups in relation to infections during the follow-up. Surgical splenectomy in children with sickle cell disease that had splenic sequestration did not affect the frequency of infectious complications during 6 years of clinical follow-up. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Health-related quality of life and adherence to hydroxyurea in adolescents and young adults with sickle cell disease.

Science.gov (United States)

Badawy, Sherif M; Thompson, Alexis A; Lai, Jin-Shei; Penedo, Frank J; Rychlik, Karen; Liem, Robert I

2017-06-01

Complications related to sickle cell disease (SCD) result in significant declines in health-related quality of life (HRQOL). While hydroxyurea reduces SCD complications, adherence remains suboptimal. The study's objectives were to assess the feasibility of Internet-based electronic assessment of HRQOL in SCD clinic and to examine the relationship between HRQOL and hydroxyurea adherence in adolescents and young adults (AYAs) with SCD. A cross-sectional survey was administered on tablets to 34 AYAs (12-22 years old) in a SCD clinic from January through December 2015. Study measures included Patient Reported Outcomes Measurement Information System (PROMIS ® ) computerized adaptive testing and ©Modified Morisky Adherence Scale 8-items (©MMAS-8). Participants (59% male, 91% Black) had median age of 13.5 (range 12-18) years. Ninety-one percent completed PROMIS® measures electronically in the clinic, meeting our feasibility criterion of ≥85% completion rate. ©MMAS-8 scores positively correlated with fetal hemoglobin (HbF) (r s = 0.34, P = 0.04) and mean corpuscular volume (MCV) (r s = 0.42, P = 0.01) and inversely correlated with fatigue (r s = -0.45, P = 0.01), depression (r s = -0.3, P = 0.08), and social isolation (r s = -0.78, P = 0.02). Low ©MMAS-8 scores, indicating poor adherence, were associated with worse fatigue (P = 0.001) and trended toward significance for pain (P = 0.07) and depression (P = 0.06). Homozygous hemoglobin S disease patients with low HbF (<16%) had worse social isolation (P = 0.04) and those with low MCV (<102 fl) reported worse fatigue (P = 0.001), pain (P = 0.01), mobility (P = 0.01), and social isolation (P = 0.04). HRQOL assessment in the SCD clinic is feasible. SCD patients with low hydroxyurea adherence and/or low HbF or MCV levels had worse HRQOL scores, particularly fatigue. Future prospective studies examining the relationship between HRQOL and hydroxyurea adherence are warranted. © 2016 Wiley Periodicals, Inc.

Priapism in paediatric patients with sickle cell disease - a report of ...

African Journals Online (AJOL)

Results: Of the 185 SCD cases, three (1.6%) had priapism. They were adolescents aged 17years, 11years and 10 years 9months respectively. Two patients had never attended a sickle cell clinic, never been on routine drugs nor received advice on oral liberal fluids intake. One patient had stuttering priapism, 24hours before ...

Family, Community, and Health System Considerations for Reducing the Burden of Pediatric Sickle Cell Disease in Uganda Through Newborn Screening

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Nancy S. Green MD

2016-04-01

Full Text Available Sickle cell disease (SCD is associated with high mortality for children under 5 years of age in sub-Saharan Africa. Newborn sickle screening program and enhanced capacity for SCD treatment are under development to reduce disease burden in Uganda and elsewhere in the region. Based on an international stakeholder meeting and a family-directed conference on SCD in Kampala in 2015, and interviews with parents, multinational experts, and other key informants, we describe health care, community, and family perspectives in support of these initiatives. Key stakeholder meetings, discussions, and interviews were held to understand perspectives of public health and multinational leadership, patients and families, as well as national progress, resource needs, medical and social barriers to program success, and resources leveraged from HIV/AIDS. Partnering with program leadership, professionals, patients and families, multinational stakeholders, and leveraging resources from existing programs are needed for building successful programs in Uganda and elsewhere in sub-Saharan Africa.

Atomic structure of the murine norovirus protruding domain and sCD300lf receptor complex.

Science.gov (United States)

Kilic, Turgay; Koromyslova, Anna; Malak, Virginie; Hansman, Grant S

2018-03-21

Human noroviruses are the leading cause of acute gastroenteritis in human. Noroviruses also infect animals such as cow, mice, cat, and dog. How noroviruses bind and enter host cells is still incompletely understood. Recently, the type I transmembrane protein CD300lf was recently identified as the murine norovirus receptor, yet it is unclear how the virus capsid and receptor interact at the molecular level. In this study, we determined the X-ray crystal structure of the soluble CD300lf (sCD300lf) and murine norovirus capsid-protruding domain complex at 2.05 Å resolution. We found that the sCD300lf binding site is located on the topside of the protruding domain and involves a network of hydrophilic and hydrophobic interactions. The sCD300lf locked nicely into a complementary cavity on the protruding domain that is additionally coordinated with a positive surface charge on the sCD300lf and a negative surface charge on the protruding domain. Five of six protruding domain residues interacting with sCD300lf were maintained between different murine norovirus strains, suggesting that the sCD300lf was capable of binding to a highly conserved pocket. Moreover, a sequence alignment with other CD300 paralogs showed that the sCD300lf interacting residues were partially conserved in CD300ld, but variable in other CD300 family members, consistent with previously reported infection selectivity. Overall, these data provide insights into how a norovirus engages a protein receptor and will be important for a better understanding of selective recognition and norovirus attachment and entry mechanisms. IMPORTANCE Noroviruses exhibit exquisite host-range specificity due to species-specific interactions between the norovirus capsid protein and host molecules. Given this strict host-range restriction it has been unclear how the viruses are maintained within a species between relatively sporadic epidemics. While much data demonstrates that noroviruses can interact with carbohydrates

Testosterone-dependent sex differences in red blood cell hemolysis in storage, stress, and disease.

Science.gov (United States)

Kanias, Tamir; Sinchar, Derek; Osei-Hwedieh, David; Baust, Jeffrey J; Jordan, Andrew; Zimring, James C; Waterman, Hayley R; de Wolski, Karen S; Acker, Jason P; Gladwin, Mark T

2016-10-01

Red blood cell (RBC) hemolysis represents an intrinsic mechanism for human vascular disease. Intravascular hemolysis releases hemoglobin and other metabolites that inhibit nitric oxide signaling and drive oxidative and inflammatory stress. Although these pathways are important in disease pathogenesis, genetic and population modifiers of hemolysis, including sex, have not been established. We studied sex differences in storage or stress-induced hemolysis in RBC units from the United States and Canada in 22 inbred mouse strains and in patients with sickle cell disease (SCD) using measures of hemolysis in 315 patients who had homozygous SS hemoglobin from the Walk-PHASST cohort. A mouse model also was used to evaluate posttransfusion recovery of stored RBCs, and gonadectomy was used to determine the mechanisms related to sex hormones. An analysis of predisposition to hemolysis based on sex revealed that male RBCs consistently exhibit increased susceptibility to hemolysis compared with females in response to routine cold storage, under osmotic or oxidative stress, after transfusion in mice, and in patients with SCD. The sex difference is intrinsic to the RBC and is not mediated by plasmatic factors or female sex hormones. Importantly, orchiectomy in mice improves RBC storage stability and posttransfusion recovery, whereas testosterone repletion therapy exacerbates hemolytic response to osmotic or oxidative stress. Our findings suggest that testosterone increases susceptibility to hemolysis across human diseases, suggesting that male sex may modulate clinical outcomes in blood storage and SCD and establishing a role for donor genetic variables in the viability of stored RBCs and in human hemolytic diseases. © 2016 AABB.

Blood transfusion in children with sickle cell disease undergoing tonsillectomy.

Science.gov (United States)

Atwood, Carlyn M; Gnagi, Sharon H; Teufel, Ronald J; Nguyen, Shaun A; White, David R

2017-12-01

Tonsillectomy is the second most common surgery in children with sickle cell disease. These children are at an increased risk of perioperative complications due to vaso-occlusive events. Although controversial, preoperative blood transfusions are sometimes given in an effort to prevent such complications. The purpose of this study is to analyze trends in the use of blood transfusion for management of children with sickle cell disease (SCD) undergoing tonsillectomy in a national database. Patients in the 1997-2012 KID with a primary procedure matching the ICD-9 procedure code for tonsillectomy (28.2-28.3) and diagnosis code for SCD (282.60-282.69) were examined. Patients were split into groups by blood transfusion status and compared across variables including complication rate, length of stay (LOS), and hospital charges. Statistical analysis included chi-square test for trend, Mann-Whitney U test, and independent t-test. 1133 patients with SCD underwent tonsillectomy. There was a strong positive correlation between increasing chronologic year and the proportion of patients receiving blood transfusions, 47 (30.1%) in 1997 to 78 (42.5%) in 2012 (r = 0.94, p = 0.005). During this period, there was no significant change in the rate of complications (r = -0.1, p = 0.87). Overall, patients receiving blood transfusion had a longer mean LOS (3.1 ± 2.4 days vs. 2.5 ± 2.2 days, p blood transfusion. The rate of complications in the transfusion group, 18 of 352(5.1%), was not significantly different (p = 0.48) from the group without transfusion, 40 of 626 (6.4%). From 1997 to 2012, there was a significant increase in the proportion of patients with SCD receiving perioperative blood transfusions for tonsillectomy. While the frequency of transfusion rose, those who received a transfusion had similar complication rates with increased charges and length of hospital stays compared to those who did not receive a transfusion. Copyright © 2017 Elsevier B.V. All

Influence of βS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease

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J. A. Moreira

2016-01-01

Full Text Available Introduction. Sickle cell disease (SCD is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF concentration. The aim of this study was to evaluate the impact of the βS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The βS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP. Statistical analyses were performed with GraphPad Prism program and the significance level was p<0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p<0.0001. The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.

Splenectomy for hematological diseases: The Qatif Central HospitalExperience

International Nuclear Information System (INIS)

Al-Salem, Ahmed H.; Naserullah, Z.; Qaisaruddin, S.; Al-Dabbous, I.; Al-Abkari, H.; Al-Jama, A.; Al-Faraj, A.; Yassin, Yassin M.

1999-01-01

In the Eastern Province of Saudi Arabia, an area known for varioushemoglobinopathies, splenectomy is performed rather frequently. This study isan analysis of our experience with splenectomy performed for varioushematological disorders between 1988 and 1997, outlining the indications,complications and outcome. This is a retrospective analysis of all patientswho had splenectomy at our hospital during this period. One hundred andforty-three patients were treated for various hematological disorders at ourhospital. These disorders included sickle cell disease (SCD) (100 patients),sickle thalassemia (S-B-thalassemia) (13 ITP) (5 patients), Gaucher's disease(2 patients), hereditary spherocytosis (1 patient), autoimmune hemolyticanemia (1 patient), thalssemia intermediate (2 patients) and chronic myeloidleukemia (1 patient). The indications for splenectomy in those with SCD andthalassemia were: hypersplenism (26 patients), major splenic sequestrationcrisis (50 patients), splenic abscess (12 patients), and massive splenicinfarction (2 patients). Splenectomy in these patients was beneficial inreducing their transfusion requirements and its attendant risks, eliminatingthe discomfort from mechanical pressure of the enlarged spleen, avoiding therisks of acute splenic sequestration crisis, and managing splenic abscess.For those with Thalassemia, total splenectomy was beneficial in reducingtheir transfusion requirements, while partial splenectomy was beneficial onlyas a temporary measure, as regrowth of splenic remnant in these patientssubsequently led to increase in their transfusion requirements. Those withITP, hereditary spherocytosis, and autoimmune hemolytic anemia showedexcellent response following splenectomy. There was no mortality, and thepostoperative morbidity was 5.6%. With careful perioperative management,splenectomy is both safe and beneficial in a selected group of patients withhematological diseases. (author)

Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

Science.gov (United States)

García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

2014-01-01

Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

Potential association between coronary artery disease and the inflammatory biomarker YKL-40 in asymptomatic patients with type 2 diabetes mellitus

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Kim Hyun

2012-07-01

Full Text Available Abstract Background Inflammation plays an important role in coronary artery disease from the initiation of endothelial dysfunction to plaque formation to final rupture of the plaque. In this study, we investigated the potential pathophysiological and clinical relevance of novel cytokines secreted from various cells including adipocytes, endothelial cells, and inflammatory cells, in predicting coronary artery disease (CAD in asymptomatic subjects with type 2 diabetes mellitus. Methods We enrolled a total of 70 asymptomatic type 2 diabetic patients without a documented history of cardiovascular disease, and determined serum levels of chemerin, omentin-1, YKL-40, and sCD26. We performed coronary computed tomographic angiography (cCTA in all subjects, and defined coronary artery stenosis ≥ 50 % as significant CAD in this study. Results Subjects were classified into two groups: patients with suspected coronary artery stenosis on cCTA (group I, n = 41 and patients without any evidence of stenosis on cCTA (group II, n = 29. Group I showed significantly higher YLK-40 levels and lower HDL-C levels than group II (p = 0.038, 0.036, respectively. Levels of chemerin, omentin-1, and sCD26 were not significantly different between the two groups. Serum YKL-40 levels were positively correlated with systolic/diastolic BP, fasting/postprandial triglyceride levels, and Framingham risk score. Furthermore, YKL-40 levels showed moderate correlation with the degree of coronary artery stenosis and the coronary artery calcium score determined from cCTA. In multivariate logistic analysis, after adjusting for age, gender, smoking history, hypertension, and LDL-cholesterol, YLK-40 levels showed only borderline significance. Conclusions YKL-40, which is secreted primarily from inflammatory cells, was associated with several CVD risk factors and was elevated in type 2 diabetic patients with suspected coronary artery stensosis on cCTA. These results suggest

Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

DEFF Research Database (Denmark)

Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

2007-01-01

CD163. However, sCD163 may be helpful in rapid identification of patients with systemic bacterial infection. If used as an adjunct to lumbar puncture, PCT and CRP had very high diagnostic accuracy for distinguishing between bacterial and viral infection in patients with spinal fluid pleocytosis. However......-operating characteristic AUCs (areas under curves). Patients were classified by 2 sets of diagnostic criteria into: A) purulent meningitis, serous meningitis or non-meningitis, and B) systemic bacterial infection, local bacterial infection or non-bacterial disease. An elevated serum level of sCD163 was the most specific......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...

The psychosocial impact of leg ulcers in patients with sickle cell disease: I don't want them to know my little secret.

Directory of Open Access Journals (Sweden)

Nkeiruka I Umeh

Full Text Available Sickle cell disease (SCD impacts millions of individuals worldwide and more than 100,000 people in the United States. Leg ulcers are the most common cutaneous manifestation of SCD. The health status of individuals living with chronic leg ulcers is not only influenced by clinical manifestations such as pain duration and intensity, but also by psychosocial factors. Garnering insights into the psychosocial impact can provide a more holistic view of their influence on quality of life.Semi-structured interviews were conducted with participants living with active SCD-associated leg ulcers or with a history of ulcers. Subjects were recruited from an ongoing study (INSIGHTS, Clin Trial.Gov NCT02156102 and consented to this qualitative phase of the study. Five areas were explored: leg ulcer pain, physical function, social-isolation, social relationships and religious support. Data was collected from 20 individuals during these interviews and a thematic analysis was performed and reported.Twenty participants with a mean age of 42.4 (SD ± 11.1years were included in the study. Major themes identified included:1 pain (acute and chronic; 2 compromised physical function as demonstrated by decreased ability to walk, run, and play sports; 3 social isolation from activities either by others or self-induced as a means of avoiding certain emotions, such as embarrassment; 4 social relationships (family support and social network; 5 support and comfort through their religion or spirituality.SCD patients with leg ulcers expressed that they experience social isolation, intense and frequent ulcer pain, and difficulty in physical function. SCD-associated leg ulcers have been studied from a clinical approach, but the psychosocial factors investigated in this study informs how quality of life is impacted by the leg ulcers.

Impairment of myocardial perfusion in children with sickle cell disease; Alteration de la perfusion myocardique chez l'enfant drepanocytaire

Energy Technology Data Exchange (ETDEWEB)

Maunoury, C. [Hopital Necker-Enfants-Malades, Service de Medecine Nucleaire, 75 - Paris (France); Acar, P. [Centre Hospitalier Universitaire, Hopital des Enfants, Service de Cardiologie Pediatrique, 31 - Toulouse (France); Montalembert, M. de [Hopital Necker-Enfants-Malades, Service de Pediatrie Generale, 75 - Paris (France)

2003-10-01

While brain, bone and spleen strokes are well documented in children with sickle cell disease (SCD), impairment of myocardial perfusion is an unknown complication. Non invasive techniques such as exercise testing and echocardiography have a low sensitivity to detect myocardial ischemia in patients with SCD. We have prospectively assessed myocardial perfusion with Tl-201 SPECT in 23 patients with SCD (10 female, 13 male, mean age 12 {+-} 5 years). Myocardial SPECT was performed after stress and 3 hours later after reinjection on a single head gamma camera equipped with a LEAP collimator (64 x 64 matrix size format, 30 projections over 180 deg C, 30 seconds per step). Left ventricular ejection fraction (LVEF) was assessed by equilibrium radionuclide angiography at rest on the same day. Myocardial perfusion was impaired in 14/23 patients: 9 reversible defects and 5 fixed defects. The left ventricular cavity was dilated in 14/23 patients. The mean LVEF was 63 {+-} 9%. There was no relationship between myocardial perfusion and left ventricular dilation or function. The frequent impairment of myocardial perfusion in children with SCD could lead to suggest a treatment with hydroxyurea, an improvement of perfusion can be noted with hydroxyurea. (author)

Tracking Spinal Cord Injury: Differences in Cytokine Expression of IGF-1, TGF- B1, and sCD95l Can Be Measured in Blood Samples and Correspond to Neurological Remission in a 12-Week Follow-Up.

Science.gov (United States)

Ferbert, Thomas; Child, Christopher; Graeser, Viola; Swing, Tyler; Akbar, Michael; Heller, Raban; Biglari, Bahram; Moghaddam, Arash

2017-02-01

Neuroinflammation presumably has an important impact on the secondary phase of spinal cord injury and is regulated by pro- and anti-inflammatory cytokines. We analyzed serum levels of three different cytokines (insulin-like-growth-factor [IGF]-1, tumor growth factor [TGF]-β1, and soluble CD 95 ligand [sCD95L]), in blood samples of 23 patients admitted with acute traumatic spinal cord injury between November 2010 and July 2013 with a follow-up period of 12 weeks. Quantification was performed using Human Quantikine Immunoassays, classification of neurological impairment was performed using the American Spinal Cord Injury Impairment Scale at time of admission and after 12 weeks. After an initial drop of all three cytokine serum levels, IGF-1, TGF-β1, and sCD95L showed significantly increased serum levels during the acute and sub-acute phases. For IGF-1 and sCD95L, we could also observe significantly higher serum levels in patients without neurological improvement compared with patients who had improvement after 12 weeks. In this study, we were able to show differences in cytokine serum levels in patients with different neurological outcome. Measuring the serum level patterns of IGF-1, TGF-β1, and sCD95L might be a useful tool for prognosis in patients with neurological improvement and tracking the pathophysiology in further studies. Further, our observations might link promising therapeutic efforts in numerous animal studies and future studies in human patients.

The radiological manifestations of sickle cell disease

International Nuclear Information System (INIS)

Madani, G.; Papadopoulou, A.M.; Holloway, B.; Robins, A.; Davis, J.; Murray, D.

2007-01-01

Sickle cell disease (SCD) is an inherited abnormality of the ss-globin chain, which causes a spectrum of haemolytic anaemias. Clinical manifestations in SCD include anaemia, jaundice, recurrent vaso-occlusive crises, and infections (particularly by encapsulated bacteria) due to functional asplenia and cerebrovascular accidents. Radiological investigations play a critical role both in the diagnosis and in the primary prevention of the complications of SCD

The radiological manifestations of sickle cell disease

Energy Technology Data Exchange (ETDEWEB)

Madani, G. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom)]. E-mail: gittamadani@yahoo.com; Papadopoulou, A.M. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom); Holloway, B. [Department of Radiology, Royal Free Hospital NHS Trust, London (United Kingdom); Robins, A. [Department of Paediatrics, Whittington Hospital NHS Trust, London (United Kingdom); Davis, J. [Department of Radiology, Whittington Hospital NHS Trust, London (United Kingdom); Murray, D. [Department of Radiology, Whittington Hospital NHS Trust, London (United Kingdom)

2007-06-15

Sickle cell disease (SCD) is an inherited abnormality of the ss-globin chain, which causes a spectrum of haemolytic anaemias. Clinical manifestations in SCD include anaemia, jaundice, recurrent vaso-occlusive crises, and infections (particularly by encapsulated bacteria) due to functional asplenia and cerebrovascular accidents. Radiological investigations play a critical role both in the diagnosis and in the primary prevention of the complications of SCD.

Information Exploration System for Sickle Cell Disease and Repurposing of Hydroxyfasudil

KAUST Repository

Essack, Magbubah

2013-06-10

Background:Sickle cell disease (SCD) is a fatal monogenic disorder with no effective cure and thus high rates of morbidity and sequelae. Efforts toward discovery of disease modifying drugs and curative strategies can be augmented by leveraging the plethora of information contained in available biomedical literature. To facilitate research in this direction we have developed a resource, Dragon Exploration System for Sickle Cell Disease (DESSCD) (http://cbrc.kaust.edu.sa/desscd/) that aims to promote the easy exploration of SCD-related data.Description:The Dragon Exploration System (DES), developed based on text mining and complemented by data mining, processed 419,612 MEDLINE abstracts retrieved from a PubMed query using SCD-related keywords. The processed SCD-related data has been made available via the DESSCD web query interface that enables: a/information retrieval using specified concepts, keywords and phrases, and b/the generation of inferred association networks and hypotheses. The usefulness of the system is demonstrated by: a/reproducing a known scientific fact, the "Sickle_Cell_Anemia-Hydroxyurea" association, and b/generating novel and plausible "Sickle_Cell_Anemia-Hydroxyfasudil" hypothesis. A PCT patent (PCT/US12/55042) has been filed for the latter drug repurposing for SCD treatment.Conclusion:We developed the DESSCD resource dedicated to exploration of text-mined and data-mined information about SCD. No similar SCD-related resource exists. Thus, we anticipate that DESSCD will serve as a valuable tool for physicians and researchers interested in SCD. © 2013 Essack et al.

Associations among emergency room visits, parenting styles, and psychopathology among pediatric patients with sickle cell.

Science.gov (United States)

Latzman, Robert D; Shishido, Yuri; Latzman, Natasha E; Elkin, T David; Majumdar, Suvankar

2014-10-01

To examine associations between frequency of emergency room (ER) visits and various parenting styles, both conjointly and interactively, and psychopathological outcomes among pediatric patients with sickle cell disease (SCD). Ninety-eight parents/caregivers of 6- to 18-year-old patients with SCD completed instruments assessing parenting style, child psychopathology, and reported on the frequency of ER visits during the previous year. ER visits were found to significantly explain Withdrawn/Depressed problems and parenting styles were found to incrementally contribute to the explanation of all forms of psychopathology. Further, Permissive parenting was found to explain Rule Breaking Behavior for those patients with low ER visit frequency but not for those with high ER visit frequency. Results of the current study confirm the importance of considering both the frequency of ER visits and parenting style in the explanation of psychopathology among pediatric patients with SCD. Results have important implications for both research and treatment. © 2014 Wiley Periodicals, Inc.

Growth and nutritional status of children with homozygous sickle cell disease

NARCIS (Netherlands)

Al-Saqladi, A.-W. M.; Cipolotti, R.; Fijnvandraat, K.; Brabin, B. J.

2008-01-01

Background: Poor growth and under-nutrition are common in children with sickle cell disease (SCD). This review summarises evidence of nutritional status in children with SCD in relation to anthropometric status, disease severity, body composition, energy metabolism, micronutrient deficiency and

Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom.

Directory of Open Access Journals (Sweden)

Mark T Gladwin

Full Text Available The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD is controversial.We evaluated the relationship between an elevated estimated pulmonary artery systolic pressure and mortality in patients with SCD. We followed patients from the walk-PHaSST screening cohort for a median of 29 months. A tricuspid regurgitation velocity (TRV≥ 3.0 m/s cuttof, which has a 67-75% positive predictive value for mean pulmonary artery pressure ≥ 25 mm Hg was used. Among 572 subjects, 11.2% had TRV ≥ 3.0 m/sec. Among 582 with a measured NT-proBNP, 24.1% had values ≥ 160 pg/mL. Of 22 deaths during follow-up, 50% had a TRV ≥ 3.0 m/sec. At 24 months the cumulative survival was 83% with TRV ≥ 3.0 m/sec and 98% with TRV 47 years, male gender, chronic transfusions, WHO class III-IV, increased hemolytic markers, ferritin and creatinine were also associated with increased risk of death.A TRV ≥ 3.0 m/sec occurs in approximately 10% of individuals and has the highest risk for death of any measured variable. The study is registered in ClinicalTrials.gov with identifier: NCT00492531.

Sudden cardiac death and coronary disease in the young

DEFF Research Database (Denmark)

Zachariasardóttir, Sára; Risgaard, Bjarke; Ågesen, Frederik Nybye

2017-01-01

BACKGROUND: Sudden cardiac death caused by coronary artery disease (CAD-SCD) is the most frequent cause of SCD in persons ..., CAD-SCD victims aged 36-49years had more severe atherosclerosis in all coronary arteries, more multi-vessel disease (29% vs. 15%, p=0.049) and less commonly (38% vs. 54%, p=0.039) acute coronary occlusion than victims ... to death. CONCLUSION: This nationwide study found several differences in the pathologic lesions of the heart in victims aged 18-35 and 36-49years, which might be associated with different disease progression leading to death in these age groups. We also report a high frequency of cardiac symptoms prior...

The role of the arginine metabolome in pain: implications for sickle cell disease

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Bakshi N

2016-03-01

Full Text Available Nitya Bakshi,1–2 Claudia R Morris3–6 1Division of Pediatric Hematology-Oncology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 2Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Atlanta, GA, USA; 3Division of Pediatric Emergency Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; 4Department of Emergency Medicine, Emory University School of Medicine, Atlanta, GA, USA; 5Emory-Children’s Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine, Atlanta, GA, USA; 6Pediatric Emergency Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA Abstract: Sickle cell disease (SCD is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO, polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its

Next-generation sequencing of 34 genes in sudden unexplained death victims in forensics and in patients with channelopathic cardiac diseases

DEFF Research Database (Denmark)

Hertz, Christin Løth; Christiansen, Sofie Lindgren; Ferrero-Miliani, Laura

2015-01-01

Sudden cardiac death (SCD) is responsible for a large proportion of sudden deaths in young individuals. In forensic medicine, many cases remain unexplained after routine postmortem autopsy and conventional investigations. These cases are called sudden unexplained deaths (SUD). Genetic testing has...... been suggested useful in forensic medicine, although in general with a significantly lower success rate compared to the clinical setting. The purpose of the study was to estimate the frequency of pathogenic variants in the genes most frequently associated with SCD in SUD cases and compare the frequency...... to that in patients with inherited cardiac channelopathies. Fifteen forensic SUD cases and 29 patients with channelopathies were investigated. DNA from 34 of the genes most frequently associated with SCD were captured using NimbleGen SeqCap EZ library build and were sequenced with next-generation sequencing (NGS...

Perioperative Management of Sickle Cell Disease.

Science.gov (United States)

Adjepong, Kwame Ofori; Otegbeye, Folashade; Adjepong, Yaw Amoateng

2018-01-01

Over 30 million people worldwide have sickle cell disease (SCD). Emergent and non-emergent surgical procedures in SCD have been associated with relatively increased risks of peri-operative mortality, vaso-occlusive (painful) crisis, acute chest syndrome, post-operative infections, congestive heart failure, cerebrovascular accident and acute kidney injury. Pre-operative assessment must include a careful review of the patient's known crisis triggers, baseline hematologic profile, usual transfusion requirements, pre-existing organ dysfunction and opioid use. Use of preoperative blood transfusions should be selective and decisions individualized based on the baseline hemoglobin, surgical procedure and anticipated volume of blood loss. Intra- and post-operative management should focus on minimizing hypoxia, hypothermia, acidosis, and intravascular volume depletion. Pre- and post-operative incentive spirometry use should be encouraged.

C-reactive Protein and Disease Outcome in Nigerian Sickle Cell ...

African Journals Online (AJOL)

Background: Evidence suggests that sickle cell disease (SCD) is associated with a chronic inflammatory state. C.reactive protein (CRP) is known to modulate inflammation. Its role in the chronic inflammation of SCD may make it valuable as a therapeutic target. Aim: The aim was to determine CRP levels in SCD subjects in ...

Prevalence of sickle cell disease among children attending plateau specialist hospital, Jos, Nigeria

Directory of Open Access Journals (Sweden)

Nanbur Stephen

2018-01-01

Full Text Available Background: An estimate of 250,000 children are born annually with sickle cell disease (SCD worldwide and 75%–85% of the affected children are born in Africa; where mortality rates for those under age 5 years range from 50% to 80%. Objective: The present study was conducted to estimate the prevalence of SCD among children in Plateau State Specialist Hospital (PSSH, Jos, Nigeria. Methodology: Ethical approval was obtained from the Health Research Ethics Committee of the Hospital. Secondary data on age, gender, and region from the case notes of infants, children and/or adolescents; who received medical care in PSSH from 2012 to 2014 were used. Data were analyzed using frequency tables and Chi-square statistics. Results: The findings revealed that the prevalence of SCD in PSSH, Jos from 2012 to 2014 was 26.9/1000 population of pediatric patients. There was a gradual increase in the prevalence rate from 25.8/1000 in 2012 to 26.8/1000 in 2013 and 28.1/1000 in 2014. However, the case fatality rate of SCD gradually decreased from 15.4% in 2012 to 11.1% in 2013 and 10.3% in 2014. Chi-square test shows that the prevalence of the disease in relation to sex, age, and residence was not statistically significant (P > 0.05. Even though the case fatality rate of the disease decreased, its prevalence increased during the study. Conclusion: Therefore, preventive measure for SCD such as premarital genetic screening and counseling should be emphasized, especially in the southern and central geopolitical zones of Plateau state, where the prevalence was found to be higher.

NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease.

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Machado, Roberto F; Hildesheim, Mariana; Mendelsohn, Laurel; Remaley, Alan T; Kato, Gregory J; Gladwin, Mark T

2011-08-01

Epidemiological studies support a hypothesis that pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) that is associated with a high risk of death and evolves as a complication of haemolytic anaemia. This fundamental hypothesis has been recently challenged and remains controversial. In order to further test this hypothesis in a large and independent cohort of SCD patients we obtained plasma samples from the Cooperative Study of Sickle Cell Disease (CSSCD) for analysis of a biomarker, N-terminal-pro brain natriuretic peptide (NT-proBNP), which is elevated in the setting of pulmonary arterial and venous hypertension. A NT-pro-BNP value previously identified to predict PH in adults with SCD was used to determine the association between the risk of mortality in 758 CSSCD participants (428 children and 330 adults). An abnormally high NT-proBNP level ≥160ng/l was present in 27·6% of adult SCD patients. High levels were associated with markers of haemolytic anaemia, such as low haemoglobin level (P<0·001), high lactate dehydrogenase (P<0·001), and high total bilirubin levels (P<0·007). A NT-proBNP level ≥160ng/l was an independent predictor of mortality (RR 6·24, 95% CI 2·9-13·3, P<0·0001). These findings provide further support for an association between haemolytic anaemia and cardiovascular complications in this patient population. © 2011 Blackwell Publishing Ltd.

The soluble receptor for vitamin B12 uptake (sCD320) increases during pregnancy and occurs in higher concentration in urine than in serum

DEFF Research Database (Denmark)

Abuyaman, Omar; Andreasen, Birgitte H; Kronborg, Camilla

2013-01-01

BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320, a receptor expressed in high quantities on human placenta. We have identified a soluble form of CD320 (sCD320) in serum and here we...... gestational weeks 17-41. sCD320, holoTC, total TC and complex formation between holoTC and sCD320 were measured by in-house ELISA methods, while creatinine was measured on the automatic platform Cobas 6000. Size exclusion chromatography was performed on a Superdex 200 column. RESULTS: Median (range) of serum...... was around two fold higher than in serum. Urinary sCD320/creatinine ratio correlated with serum sCD320 and reached a peak median level of 53 (30-101) pmol/mmol creatinine (week 35). sCD320 present in serum and urine showed the same elution pattern upon size exclusion chromatography. CONCLUSION: We report...

Non-invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease.

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Caboot, Jason B; Jawad, Abbas F; McDonough, Joseph M; Bowdre, Cheryl Y; Arens, Raanan; Marcus, Carole L; Mason, Thornton B A; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L

2012-08-01

Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and -0.22% for MetHb. The precision of the measured SpCO was ± 2.1% within a COHb range of 0.4-6.1%, and the precision of the measured SpMet was ± 0.33% within a MetHb range of 0.1-1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. Copyright © 2012 Wiley Periodicals, Inc.

Role of hydroxycarbamide in prevention of complications in patients with sickle cell disease

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NM Wiles

2009-09-01

Full Text Available NM Wiles, J HowardDepartment of Haematology, St Thomas’ Hospital, Westminster, Bridge Road, London, SE1 7EH, UKAbstract: Sickle cell disease (SCD is a genetically inherited condition caused by a point mutation in the beta globin gene. This results in the production of the abnormal hemoglobin, sickle hemoglobin (HbS. Hydroxycarbamide, is an antimetabolite/cytotoxic which works by inhibiting ribonucleotide reductase, blocking the synthesis of DNA and arresting cells in the S phase. In sickle cell anemia, it promotes fetal hemoglobin (HbF synthesis, improves red cell hydration, decreases neutrophil and platelet count, modifies red cell endothelial cell interactions and acts as a nitric oxide donor. Trials have shown the clinical benefit of hydroxycarbamide in a subpopulation of adult patients with SCD, with a 44% reduction in the median annual rate of painful crises, a decrease in the incidence of acute chest syndrome and an estimated 40% reduction in overall mortality over a 9-year observational period. Its use in pediatrics has also been well established; trials have shown it is well tolerated and does not impair growth or development. In addition it decreases the number and duration of hospital attendences. A number of emerging uses of hydroxycarbamide currently are being investigated, such as stroke prevention.Keywords: sickle cell anemia, hydroxycarbamide, hydroxyurea, maximum tolerated dose, vaso-occlusive crisis

Connecting the dots: could microbial translocation explain commonly reported symptoms in HIV disease?

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Wilson, Natalie L; Vance, David E; Moneyham, Linda D; Raper, James L; Mugavero, Michael J; Heath, Sonya L; Kempf, Mirjam-Colette

2014-01-01

Microbial translocation within the context of HIV disease has been described as one of the contributing causes of inflammation and disease progression in HIV infection. HIV-associated symptoms have been related to inflammatory markers and sCD14, a surrogate marker for microbial translocation, suggesting a plausible link between microbial translocation and symptom burden in HIV disease. Similar pathophysiological responses and symptoms have been reported in inflammatory bowel disease. We provide a comprehensive review of microbial translocation, HIV-associated symptoms, and symptoms connected with inflammation. We identify studies showing a relationship among inflammatory markers, sCD14, and symptoms reported in HIV disease. A conceptual framework and rationale to investigate the link between microbial translocation and symptoms is presented. The impact of inflammation on symptoms supports recommendations to reduce inflammation as part of HIV symptom management. Research in reducing microbial translocation-induced inflammation is limited, but needed, to further promote positive health outcomes among HIV-infected patients. Published by Elsevier Inc.

Acute pain in children and adults with sickle cell disease: management in the absence of evidence-based guidelines.

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Field, Joshua J; Knight-Perry, Jessica E; Debaun, Michael R

2009-05-01

Acute, vaso-occlusive pain is the most characteristic complication of sickle cell disease (SCD). Although there has been rigorous work examining the pathogenesis of vaso-occlusion, fewer studies have focused on approaches to the clinical management of acute pain. In this review, we will examine the epidemiology and management strategies of acute pain events and we will identify limitations in the best available studies. Most acute pain events in adults with SCD are managed at home without physician contact. Prior descriptions of the natural history of pain episodes from the Cooperative Study of Sickle Cell Disease relied on physician contact, limiting the generalizability of these findings to current practice. Patient-controlled analgesia has replaced on-demand therapy to become the standard for management of severe pain events in children and adults with SCD requiring hospital admission. Unfortunately, most clinical practice guidelines for the management of acute pain are not based on randomized clinical trials. As a result, our practice of pain management is primarily limited to expert opinion and inferences from observational studies. Additional clinical trials in management of acute pain in children and adults with SCD are critical for the development of evidence-based guidelines.

CDC Grand Rounds: Improving the Lives of Persons with Sickle Cell Disease.

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Hulihan, Mary; Hassell, Kathryn L; Raphael, Jean L; Smith-Whitley, Kim; Thorpe, Phoebe

2017-11-24

Approximately 100,000 Americans have sickle cell disease (SCD), a group of recessively inherited red blood cell disorders characterized by abnormal hemoglobin, called hemoglobin S or sickle hemoglobin, in the red blood cells. Persons with hemoglobin SS or hemoglobin Sß 0 thalassemia, also known as sickle cell anemia (SCA), have the most severe form of SCD. Hemoglobin SC disease and hemoglobin Sß + thalassemia are other common forms of SCD. Red blood cells that contain sickle hemoglobin are inflexible and can stick to vessel walls, causing a blockage that slows or stops blood flow. When this happens, oxygen cannot reach nearby tissues, leading to attacks of sudden, severe pain, called pain crises, which are the clinical hallmark of SCD. The red cell sickling and poor oxygen delivery can also cause damage to the brain, spleen, eyes, lungs, liver, and multiple other organs and organ systems. These chronic complications can lead to increased morbidity, early mortality, or both. Tremendous strides in treating and preventing the complications of SCD have extended life expectancy. Now, nearly 95% of persons born with SCD in the United States reach age 18 years (1); however, adults with the most severe forms of SCD have a life span that is 20-30 years shorter than that of persons without SCD (2).

Controlling sickle cell disease in Ghana ethics and options | Edwin ...

African Journals Online (AJOL)

Sickle Cell Disease (SCD) is a significant public health burden in Ghana. Recent studies indicate that 2% of Ghanaian newborns are affected by SCD; one in three Ghanaians has the hemoglobin S and/or C gene. As a means of controlling the disease, some authorities have recommended prenatal diagnosis (PND) and ...

Improved Guideline Adherence With Integrated Sickle Cell Disease and Asthma Care.

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McClain, Brandi L; Ivy, Zalaya K; Bryant, Valencia; Rodeghier, Mark; DeBaun, Michael R

2016-07-01

In children with sickle cell disease (SCD), concomitant asthma is associated with increased morbidity and mortality when compared with children with SCD without asthma. Despite the well-established burden of asthma in children with SCD, no paradigm of care exists for the co-management of these two diseases. To address this gap, an integrated SCD and asthma clinic was created in a community health center that included (1) a dual respiratory therapist/asthma case manager; (2) an SCD nurse practitioner with asthma educator certification; (3) an onsite pulmonary function test laboratory; (4) a pediatric hematologist with expertise in managing SCD and asthma; and (5) application of the National Asthma Education and Prevention Program guidelines. A before (2010-2012) and after (2013-2014) study design was used to assess for improved quality of care with implementation of an integrative care model among 61 children with SCD and asthma followed from 2010 to 2014. Asthma action plan utilization after initial diagnosis increased with the integrative care model (n=16, 56% before, 100% after, p=0.003), as did the use of spirometry in children aged ≥5 years (n=41, 65% before, 95% after, pintegrative care model for SCD and asthma improved evidence-based asthma care, longer follow-up and evaluation will be needed to determine the impact on SCD-related morbidity. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Pediatric to Adult Care Transition: Perspectives of Young Adults With Sickle Cell Disease.

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Porter, Jerlym S; Wesley, Kimberly M; Zhao, Mimi S; Rupff, Rebecca J; Hankins, Jane S

2017-10-01

The aim of this study was to explore perspectives of transition and transition readiness of young adult patients (YAs) with sickle cell disease (SCD) who have transitioned to adult health care. In all, 19 YAs with SCD (ages 18-30 years) participated in one of three focus groups and completed a brief questionnaire about transition topics. Transcripts were coded and emergent themes were examined using the social-ecological model of adolescent and young adult readiness for transition (SMART). Themes were consistent with most SMART components. Adult provider relationships and negative medical experiences emerged as salient factors. YAs ranked choosing an adult provider, seeking emergency care, understanding medications/medication adherence, knowing SCD complications, and being aware of the impact of health behaviors as the most important topics to include in transition programming. The unique perspectives of YAs can inform the development and evaluation of SCD transition programming by incorporating the identified themes. © The Author 2017. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Assessing the Effect of an Educational Intervention on Nurses' and Patient Care Assistants' Comprehension and Documentation of Functional Ability in Pediatric Patients with Sickle Cell Disease.

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Bernier, Katherine M; Strobel, Megan; Lucas, Ruth

2018-04-13

In 2014, the Youth Acute Pain Functional Ability Questionnaire (YAPFAQ) was developed to investigate patient's self-rated functional ability during times of acute pain in the inpatient clinical setting. Although it has great potential, the application of this tool has not been made a standard of care. The purpose of this multiple methods study was to determine if, through an educational intervention, hospital staff could consistently document the YAPFAQ in children with sickle cell disease (SCD) during a vaso-occlusive episode. Twenty-two staff members participated in an educational intervention and semi-structured group discussions. Pre/post surveys measured knowledge of the YAPFAQ before and after the intervention. Group discussions were recorded, transcribed verbatim, and analyzed for thematic clusters. Retrospective chart reviews of children with SCD were reviewed for YAPFAQ documentation frequency before and after the intervention. Staff knowledge of who completes the YAPFAQ increased after the intervention, (pcontinues to hold high potential for directing nursing care, but requires staff investment for clinical practice change. A seamless integration between nursing education and translation through EHR is recommended as technology continues to integrate into nursing practice. Copyright © 2018 Elsevier Inc. All rights reserved.

Associates of School Absenteeism in Adolescents With Sickle Cell Disease

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Schwartz, Lisa A.; Radcliffe, Jerilynn; Barakat, Lamia P.

2009-01-01

Background Despite high rates of school absenteeism in adolescents with sickle cell disease (SCD), the issue remains understudied. Potential associates of school absenteeism in adolescents with SCD include demographic (age, income), psychosocial (IQ, self-efficacy, competence, internalizing symptoms, negative thinking), and health-related (hemoglobin, health-care utilization, pain, disease knowledge). Procedure Forty participants ages 12–18 completed measures of psychosocial functioning, IQ, and pain. Medical chart reviews identified other health-related variables. A subsample also completed an assessment of goals. Using school records, absenteeism was the percent of school days missed in the previous year. Correlations tested associates of absenteeism and linear regression tested a model of absenteeism. Results Participants missed an average of 12% of the school year and more than 35% missed at least 1 month of school. Health-related and psychosocial variables, but not demographic variables, correlated with absenteeism. Attendance at clinic appointments and parent-reported teen pain frequency were significant associates of absenteeism in the regression model. For those who completed goal assessment, over 40% of goals identified were academically focused. Absenteeism was positively related to current academic goals and health-related hindrance of academic goals, and negatively related to future-oriented academic goals. Conclusions School absenteeism is a significant problem for adolescents with SCD despite the presence of academic goals. Collaboration between schools, parents, patients, and providers to understand and manage the impact of SCD on school attendance is recommended. PMID:19006248

Sickle cell disease in Sierra Leone: a neglected problem | Roberts ...

African Journals Online (AJOL)

Eleven (2.4%) were Sickle Cell-HbC disease, median age 14 years. Patients demonstrated many of the typical features of SCD. The most common reason for hospital admission was bone pain crisis associated with an infection, followed by severe anemia. Aseptic necrosis of the femoral head, leg ulcers, septic osteomyelitis ...

Survival among children and adults with sickle cell disease in Belgium: Benefit from hydroxyurea treatment.

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Lê, Phu Quoc; Gulbis, Béatrice; Dedeken, Laurence; Dupont, Sophie; Vanderfaeillie, Anna; Heijmans, Catherine; Huybrechts, Sophie; Devalck, Christine; Efira, André; Dresse, Marie-Françoise; Rozen, Laurence; Benghiat, Fleur Samantha; Ferster, Alina

2015-11-01

To evaluate the survival of patients with sickle cell disease (SCD) recorded in the Belgian SCD Registry and to assess the impact of disease-modifying treatments (DMT). The Registry created in 2008 included patients of eight centers. All available data in 2008 were retrospectively encoded in the database. After 2008 and until 2012, all data were recorded prospectively for already registered patients as well as newly diagnosed subjects. Data were registered from neonatal screening or from diagnosis (first contact) until last follow-up or death. Data included diagnosis, demography, and outcome data. We collected data from 469 patients over a 5,110 patient years (PY) follow-up period. The global mortality rate was low (0.25/100 PY), although 13 patients died (2.8%) and was similar between children, adolescents (10-18 years), and young adults (P = 0.76). Out of the cohort, 185 patients received hydroxyurea at last follow-up (median duration of treatment: 10.3 years), 90 underwent hematopoietic stem cell transplantation (HSCT), 24 were chronically transfused, and 170 had never had any DMT. Hydroxyurea showed significant benefit on patients outcome as reflected by a lower mortality rate compared to transplanted individuals or people without DMT (0.14, 0.36, and 0.38 per 100 PY, respectively) and by higher Kaplan-Meier estimates of 15 year survival (99.4%) compared to HSCT (93.8%; P = 0.01) or no DMT groups (95.4%; P = 0.04). SCD mortality in Belgium is low with no increase observed in young adults. Patients treated with hydroxyurea demonstrate a significant benefit in survival when compared to those without DMT or transplanted. © 2015 Wiley Periodicals, Inc.

Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort

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Willis, R; Seif, AM; McGwin, G; Martinez-Martinez, LA; González, EB; Dang, N; Papalardo, E; Liu, J; Vilá, LM; Reveille, JD; Alarcón, GS; Pierangeli, SS

2013-01-01

Objective We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA). Methods Plasma/serum samples from SLE patients (n=35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls. Results Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α (p=0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores (p=0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α (p=0.0087). Conclusions Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE. PMID:22343096

Prophylactic red blood cell exchange may be beneficial in the management of sickle cell disease in pregnancy.

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Asma, Suheyl; Kozanoglu, Ilknur; Tarım, Ebru; Sarıturk, Cagla; Gereklioglu, Cigdem; Akdeniz, Aydan; Kasar, Mutlu; Turgut, Nurhilal H; Yeral, Mahmut; Kandemir, Fatih; Boga, Can; Ozdogu, Hakan

2015-01-01

Sickle cell disease (SCD) is associated with chronic hemolysis and painful episodes. Pregnancy accelerates sickle cell complications, including prepartum and postpartum vasoocclusive crisis, pulmonary complications, and preeclampsia or eclampsia. Fetal complications include preterm birth and its associated risks, intrauterine growth restriction, and a high rate of perinatal mortality. The purpose of this study was to evaluate pregnancy outcomes in patients with SCD who underwent planned preventive red blood cell exchange (RBCX). We retrospectively evaluated the complications of SCD in 37 pregnant patients. Patients with SCD who had undergone prophylactic RBCX were compared with a control group who had not undergone RBCX during pregnancy. Forty-three exchange procedures were performed in 24 patients. The control group comprised 13 patients with a mean age of 27.4 ± 3.3 years who had not undergone RBCX during pregnancy. Four of the five patients who developed a vasoocclusive crisis died. There was a significant difference in maternal mortality between the study and control groups (p = 0.011). There was also a significant difference in the incidence of vasoocclusive crisis between the study and control groups. One fetal death occurred in the 20th gestational week in a patient in the control group, although there were no postpartum complications in either the babies or the mothers in the control group. This study has demonstrated that prophylactic RBCX during pregnancy is a feasible and safe procedure for prevention of complications. Given the decrease in the risks of transfusion, RBCX warrants further study. © 2014 AABB.

Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

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Smith, Kelsey E.; Schatz, Jeffrey

2017-01-01

Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD. PMID:27759435

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease.

Science.gov (United States)

Hosseini, Poorya; Abidi, Sabia Z; Du, E; Papageorgiou, Dimitrios P; Choi, Youngwoon; Park, YongKeun; Higgins, John M; Kato, Gregory J; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T C

2016-08-23

Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.

Outpatient Pain Predicts Subsequent One-Year Acute Health Care Utilization Among Adults With Sickle Cell Disease

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Ezenwa, Miriam O.; Molokie, Robert E.; Wang, Zaijie Jim; Yao, Yingwei; Suarez, Marie L.; Angulo, Veronica; Wilkie, Diana J.

2014-01-01

Context Patient demographic and clinical factors have known associations with acute health care utilization (AHCU) among patients with sickle cell disease (SCD), but it is unknown if pain measured predominantly in an outpatient setting is a predictor of future AHCU in patients with SCD. Objectives To determine whether multidimensional pain scores obtained predominantly in an outpatient setting predicted subsequent one-year AHCU by 137 adults with SCD and whether the pain measured at a second visit also predicted AHCU. Methods Pain data included the Composite Pain Index (CPI), a single score representative of a multidimensional pain experience (number of pain sites, intensity, quality, and pattern). Based on the distribution of AHCU events, we divided patients into three groups: (1) zero events (Zero), (2) 1–3 events (Low), or (3) 4–23 events (High). Results The initial CPI scores differed significantly by the three groups (F(2,134)=7.38, P=0.001). Post hoc comparisons showed that the Zero group had lower CPI scores than both the Low group (Pgroup (Page, and CPI scores (at both measurement times) were statistically significant predictors of utilization events. Pain intensity scores at both measurement times were significant predictors of utilization, but other pain scores (number of pain sites, quality, and pattern) were not. Conclusion Findings support use of outpatient CPI scores or pain intensity and age to identify at-risk young adults with SCD who are likely to benefit from improved outpatient pain management plans. PMID:24636960

Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice.

Science.gov (United States)

Baig, Shanat; Edward, Nicky C; Kotecha, Dipak; Liu, Boyang; Nordin, Sabrina; Kozor, Rebecca; Moon, James C; Geberhiwot, Tarekegn; Steeds, Richard P

2017-10-17

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.

AAPT Diagnostic Criteria for Chronic Sickle Cell Disease Pain.

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Dampier, Carlton; Palermo, Tonya M; Darbari, Deepika S; Hassell, Kathryn; Smith, Wally; Zempsky, William

2017-05-01

Pain in sickle cell disease (SCD) is associated with increased morbidity, mortality, and high health care costs. Although episodic acute pain is the hallmark of this disorder, there is an increasing awareness that chronic pain is part of the pain experience of many older adolescents and adults. A common set of criteria for classifying chronic pain associated with SCD would enhance SCD pain research efforts in epidemiology, pain mechanisms, and clinical trials of pain management interventions, and ultimately improve clinical assessment and management. As part of the collaborative effort between the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks public-private partnership with the U.S. Food and Drug Administration and the American Pain Society, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative developed the outline of an optimal diagnostic system for chronic pain conditions. Subsequently, a working group of experts in SCD pain was convened to generate core diagnostic criteria for chronic pain associated with SCD. The working group synthesized available literature to provide evidence for the dimensions of this disease-specific pain taxonomy. A single pain condition labeled chronic SCD pain was derived with 3 modifiers reflecting different clinical features. Future systematic research is needed to evaluate the feasibility, validity, and reliability of these criteria. An evidence-based classification system for chronic SCD pain was constructed for the Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks-American Pain Society Pain Taxonomy initiative. Applying this taxonomy may improve assessment and management of SCD pain and accelerate research on epidemiology, mechanisms, and treatments for chronic SCD pain. Copyright © 2017 The Authors. Published by

Pain Management for Sickle Cell Disease in the Pediatric Emergency Department: Medications and Hospitalization Trends.

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Cacciotti, Chantel; Vaiselbuh, Sarah; Romanos-Sirakis, Eleny

2017-10-01

The majority of emergency department (ED) visits and hospitalizations for patients with sickle cell disease (SCD) are pain related. Adequate and timely pain management may improve quality of life and prevent worsening morbidities. We conducted a retrospective chart review of pediatric patients with SCD seen in the ED, selected by sickle cell-related ICD-9 codes. A total of 176 encounters were reviewed from 47 patients to record ED pain management and hospitalization trends. Mean time to pain medication administration was 63 minutes. Patients received combination (nonsteroidal anti-inflammatory drug [NSAID] + narcotic) pain medications for initial treatment at a minority of ED encounters (19%). A higher percentage of patients who received narcotics alone as initial treatment were hospitalized as compared with those who received combination treatment initially ( P= 0.0085). Improved patient education regarding home pain management as well as standardized ED guidelines for assessment and treatment of sickle cell pain may result in superior and more consistent patient care.

Cerebro vascular accident in sickle cell disease

International Nuclear Information System (INIS)

Alam, M.; Lodhi, M.A.; Khan, D.

2003-01-01

Sickle cell disease (SCD) is a common inherited hemoglobin disorder characterized by the presence of sickle shaped erythrocytes in the blood. It can cause stroke in around 10% of children. Repeated blood transfusions are often used in an attempt to dilute blood thus reducing the risk of vaso-occlusion and stroke. We report a case of an 11 years old girl, known patient of sickle cell disease, who did not follow regular blood transfusion protocol and as a result presented with recurrent stroke. (author)

[Usefulness of sCD14-ST in the diagnosis of sepsis in patient with renal failure].

Science.gov (United States)

Galeano, Dario; Zanoli, Luca; Fatuzzo, Pasquale; Granata, Antonio

2016-01-01

Since many years, researchers have focused their studies to find out early sepsis biomarkers for the purpose of gaining time in the application of early goal-directed therapy protocol. Procalcitonin (PCT) is a reliable biomarker for sepsis, although it has a low specificity and prognostic value. Other recently proposed sepsis biomarkers such as interleukins, C-reactive protein (CRP), myeloid cells expressing triggering receptor-1 (TREM-1) and soluble urokinase-type plasminogen activator receptor (suPAR) still have a controversial and uncertain clinical value. In 2004 a new biomarker, soluble CD14 SubType (sCD14-ST, Presepsin), with a good performance in the diagnosis and prognostic evaluation of sepsis has been proposed. First studies highlighted that Presepsin is highly sensitive and specific at the same time. However, further studies on the clinical value of Presepsin are needed, particularly in order to explain the relationship between Presepsin and kidney failure. Indeed, Presepsin is a 13 KDa molecule theoretically totally filtered by glomerulus and reabsorbed and metabolized by proximal convoluted tubules. Therefore, the Presepsin plasmatic level could be highly influenced by an acute kidney injury in the course of sepsis or by a pre-existing chronic kidney disease. In this article we reviewed the latest evidences about the diagnostic and prognostic performances of Presepsin as a sepsis biomarker. We evaluated the usefulness of Presepsin in the context of acute and chronic kidney dysfunction. The great number of articles have been collected and the thorough revision of data from the nephrologists perspective let us consider this work exhaustive and scientifically reliable, although concise: a good starting point for the physician who wants to make use of Presepsin.

Antibody development in pediatric sickle cell patients undergoing erythrocytapheresis.

Science.gov (United States)

Godfrey, Gwendolyn J; Lockwood, William; Kong, Maiying; Bertolone, Salvatore; Raj, Ashok

2010-12-01

Erythrocytapheresis, or red blood cell exchange transfusion (RBCX), with donor red blood cell (RBC) units is now increasingly used in the treatment of acute and chronic complications of sickle cell disease (SCD). As in all transfusions, RCBX carries a risk of immunization against foreign antigen on transfused cells. However, by selecting donor units with RBC phenotypes similar to the patient, the risk of allo- and autoimmunization can be reduced. The formation of RBC alloantibodies and/or autoantibodies in 32 multitransfused pediatric SCD patients undergoing monthly RBCX over a 11-year period (12/1998 to 12/2009) was evaluated utilizing a retrospective patient chart review at Kosair Children's Hospital, Louisville, Kentucky. After starting C, E, K antigen-matched RBCX, the rate of clinically significant allo-immunization decreased from 0.189/100 to 0.053/100 U, with a relative risk of 27.9%. Likewise, the rate of autoimmunization decreased from 0.063/100 to 0.035/100 U, with a relative risk of 55.9%. After controlling for clinically insignificant antibodies, our auto- and alloimmunization rate was much less than previously reported values. In addition, the incidence of clinically significant allo- and autoimmunization decreased in our patient population after starting minor antigen-matched RBCX. These results suggest that by matching selected RBC phenotypes, there may be an association in the risk of allo- and autoimmunization of multi-transfused SCD patients.

Clinical relevance of pre and post-transplant immune markers in kidney allograft recipients: anti-HLA and MICA antibodies and serum levels of sCD30 and sMICA.

Science.gov (United States)

Solgi, Ghasem; Furst, Daniel; Mytilineos, Joannis; Pourmand, Gholamreza; Amirzargar, Ali Akbar

2012-03-01

This retrospective study aims to determine the prognostic values of HLA and MICA antibodies, serum levels of sCD30 and soluble form of MHC class I related chain A (sMICA) in kidney allograft recipients. Sera samples of 40 living unrelated donor kidney recipients were tested by ELISA and Flow beads techniques for the presence of anti HLA and MICA antibodies and the contents of sCD30 and sMICA. HLA and MICA antibody specification was performed by LABScreen single antigen beads to determine whether the antibodies were directed against donor mismatches. Within first year post operatively 9 of 40 patients (22.5%) showed acute rejection episodes (ARE) that four of them lost their grafts compared to 31 functioning transplants (P=0.001). The presence of HLA antibodies before and after transplantation was significantly associated with ARE (P=0.01 and P=0.02 respectively). Sensitization to HLA class II antigens pre-transplant was strongly associated with higher incidence of ARE (P=0.004). A significant correlation was found between ARE and appearance of non-donor specific antibodies (P=0.02). HLA antibody positive patients either before or after transplantation showed lower graft survival rates than those without antibodies during three years follow-up (P=0.04 and P=0.02). Anti-MICA antibodies were observed in 8/40(20%) and 5/40(12.5%) of patients pre and post-transplant respectively. Coexistence of HLA and MICA antibodies was shown in 2 of 4 cases with graft loss. A significant increased level of sCD30 at day 14 (P=0.001) and insignificant decreased levels of sMICA pre and post operatively were detected in rejecting transplants compared to functioning graft group. Our findings support the view that monitoring of HLA and MICA antibodies as well as sCD30 levels early after transplant has predictive value for early and late allograft dysfunctions and the presence of these factors are detrimental to graft function and survival. Copyright © 2012 Elsevier B.V. All rights

Technology Access and Smartphone App Preferences for Medication Adherence in Adolescents and Young Adults With Sickle Cell Disease.

Science.gov (United States)

Badawy, Sherif M; Thompson, Alexis A; Liem, Robert I

2016-05-01

Hydroxyurea is the only Food and Drug Administration approved medication for sickle cell disease (SCD) with short- and long-term benefits for both morbidity and mortality. However, hydroxyurea underutilization and adherence remain challenges for patients with SCD. The objectives of this study were to determine access to technology among adolescents and young adults (AYA) with SCD and to identify their preferred technology-based strategies for improving medication adherence. A cross-sectional survey was administered in a variety of clinical settings from October 2014 through May 2015 to AYA (12-22 years) with SCD (all genotypes) followed in a Comprehensive Sickle Cell Program. Eighty of 107 eligible participants completed the survey for a 75% response rate. Participants (51% female, 94% Black) had a mean age of 15.3 ± 2.8 years. Most participants (75%) were on a daily medication with about half on hydroxyurea. Forgetfulness (67%) was the most common barrier to medication adherence. The majority of participants (85%) owned smartphones and either owned or had access to electronic tablets (83%), laptops (72%), or desktops (70%). Of the proposed smartphone app features, daily medication reminders were ranked first most frequently, followed by education about SCD, adherence text prompts, education about SCD medications, and medication log. The majority of our AYA with SCD owned smartphones and had access to other electronic devices. Our survey results provided valuable insight into the preferred app features and optimal strategies for developing technology-based interventions, such as a multicomponent app, to increase medication adherence for AYA with SCD or other chronic conditions. © 2016 Wiley Periodicals, Inc.

Hydroxyurea therapy in adult Nigerian sickle cell disease: a ...

African Journals Online (AJOL)

Background: The clinical prospects of hydroxyurea therapy in the management of sickle cell disease (SCD) require evaluation in the Nigerian setting to develop indigenous guidelines. This survey examines the pattern of hydroxyurea therapy, its clinico-haematologic benefits and safety profile in Nigerian SCD subjects.

The impact of preparation and support procedures for children with sickle cell disease undergoing MRI

International Nuclear Information System (INIS)

Cejda, Katherine R.; Smeltzer, Matthew P.; Hansbury, Eileen N.; McCarville, Mary Elizabeth; Helton, Kathleen J.; Hankins, Jane S.

2012-01-01

Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30-60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children's ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n = 60) or liver R2*MRI (n = 11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not 30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR = 4.1 (P = 0.04) and OR = 8.5 (P < 0.01) when adjusting for age. PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia. (orig.)

The impact of preparation and support procedures for children with sickle cell disease undergoing MRI

Energy Technology Data Exchange (ETDEWEB)

Cejda, Katherine R. [St. Jude Children' s Research Hospital, Child Life Program, Memphis, TN (United States); Smeltzer, Matthew P. [St. Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Hansbury, Eileen N. [Baylor International Hematology Center of Excellence and the Texas Children' s Center for Global Health, Houston, TX (United States); McCarville, Mary Elizabeth; Helton, Kathleen J. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Hankins, Jane S. [St. Jude Children' s Research Hospital, Department of Hematology, Memphis, TN (United States)

2012-10-15

Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30-60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children's ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n = 60) or liver R2*MRI (n = 11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not 30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR = 4.1 (P = 0.04) and OR = 8.5 (P < 0.01) when adjusting for age. PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia. (orig.)

Evidence-Based Practice Standard Care for Acute Pain Management in Adults With Sickle Cell Disease in an Urgent Care Center.

Science.gov (United States)

Kim, Sunghee; Brathwaite, Ron; Kim, Ook

Vaso-occlusive episodes (VOEs) with sickle cell disease (SCD) require opioid treatment. Despite evidence to support rapid pain management within 30 minutes, care for these patients does not consistently meet this benchmark. This quality improvement study sought to decrease the first analgesic administration time, increase patient satisfaction, and expedite patient flow. A prospective pre-/postevaluation design was used to evaluate outcomes with patients 18 years or older with VOEs in an urgent care (UC) center after implementation of evidence-based practice standard care (EBPSC). A pre- and postevaluation survey of SCD patients' satisfaction with care and analogous surveys of the UC team to assess awareness of EBPSC were used. A retrospective review of the electronic medical records of patients with VOEs compared mean waiting time from triage to the first analgesic administration and the mean length of stay (LOS) over 6 months. Implementing EBPSC decreased the mean time of the first analgesic administration (P = .001), significantly increased patient satisfaction (P = .002), and decreased the mean LOS (P = .010). Implementing EBPSC is a crucial step for improving the management of VOEs and creating a positive patient experience. The intervention enhances the quality of care for the SCD population in a UC center.

Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

Science.gov (United States)

Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

2006-04-27

In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

Phase 1 Study of a Sulforaphane-Containing Broccoli Sprout Homogenate for Sickle Cell Disease.

Directory of Open Access Journals (Sweden)

Jennifer F Doss

Full Text Available Sickle cell disease (SCD is the most common inherited hemoglobinopathy worldwide. Our previous results indicate that the reduced oxidative stress capacity of sickle erythrocytes may be caused by decreased expression of NRF2 (Nuclear factor (erythroid-derived 2-like 2, an oxidative stress regulator. We found that activation of NRF2 with sulforaphane (SFN in erythroid progenitors significantly increased the expression of NRF2 targets HMOX1, NQO1, and HBG1 (subunit of fetal hemoglobin in a dose-dependent manner. Therefore, we hypothesized that NRF2 activation with SFN may offer therapeutic benefits for SCD patients by restoring oxidative capacity and increasing fetal hemoglobin concentration. To test this hypothesis, we performed a Phase 1, open-label, dose-escalation study of SFN, contained in a broccoli sprout homogenate (BSH that naturally contains SFN, in adults with SCD. The primary and secondary study endpoints were safety and physiological response to NRF2 activation, respectively. We found that BSH was well tolerated, and the few adverse events that occurred during the trial were not likely related to BSH consumption. We observed an increase in the mean relative whole blood mRNA levels for the NRF2 target HMOX1 (p = 0.02 on the last day of BSH treatment, compared to pre-treatment. We also observed a trend toward increased mean relative mRNA levels of the NRF2 target HBG1 (p = 0.10 from baseline to end of treatment, but without significant changes in HbF protein. We conclude that BSH, in the provided doses, is safe in stable SCD patients and may induce changes in gene expression levels. We therefore propose investigation of more potent NRF2 inducers, which may elicit more robust physiological changes and offer clinical benefits to SCD patients. Trial registration: ClinicalTrials.gov NCT01715480.

High serum soluble CD30 does not predict acute rejection in liver transplant patients.

Science.gov (United States)

Matinlauri, I; Höckerstedt, K; Isoniemi, H

2006-12-01

Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia

DEFF Research Database (Denmark)

Vojdeman, Fie J; Herman, Sarah E M; Kirkby, Nikolai

2017-01-01

CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early...... had independent prognostic value. Following chemo-immunotherapy, sCD52 decreased in parallel with leukocytes while during ibrutinib treatment and ibrutinib-induced ymphocytosis, sCD52 decreased along with lymph node reductions. In vitro IgM stimulation of CLL cells led to increased sCD52 levels...

National registry of hemoglobinopathies in Spain (REPHem).

Science.gov (United States)

Cela, Elena; Bellón, José M; de la Cruz, María; Beléndez, Cristina; Berrueco, Rubén; Ruiz, Anna; Elorza, Izaskun; Díaz de Heredia, Cristina; Cervera, Aurea; Vallés, Griselda; Salinas, J Antonio; Coll, M Teresa; Bermúdez, Mar; Prudencio, Marta; Argilés, Bienvenida; Vecilla, Cruz

2017-07-01

Although highly prevalent throughout the world, the accurate prevalence of hemoglobinopathies in Spain is unknown. This study presents data on the national registry of hemoglobinopathies of patients with thalassemia major (TM), thalassemia intermedia (TI), and sickle cell disease (SCD) in Spain created in 2014. Fifty centers reported cases retrospectively. Data were registered from neonatal screening or from the first contact at diagnosis until last follow-up or death. Data of the 715 eligible patients were collected: 615 SCD (497 SS, 64 SC, 54 SBeta phenotypes), 73 thalassemia, 9 CC phenotype, and 18 other variants. Most of the SCD patients were born in Spain (65%), and 51% of these were diagnosed at newborn screening. Median age at the first diagnosis was 0.4 years for thalassemia and 1.0 years for SCD. The estimated incidence was 0.002 thalassemia cases and 0.03 SCD cases/1,000 live births. Median age was 8.9 years (0.2-33.7) for thalassemia and 8.1 years (0.2-32.8) for SCD patients. Stroke was registered in 16 SCD cases. Transplantation was performed in 43 TM and 23 SCD patients at a median age of 5.2 and 7.8 years, respectively. Twenty-one patients died (3 TM, 17 SCD, 1 CC) and 200 were lost to follow-up. Causes of death were related to transplantation in three patients with TM and three patients with SCD. Death did not seem to be associated with SCD in six patients, but nine patients died secondary to disease complications. Overall survival was 95% at 15 years of age. The registry provides data about the prevalence of hemoglobinopathies in Spain and will permit future cohort studies and the possibility of comparison with other registries. © 2016 Wiley Periodicals, Inc.

Epidemiology and treatment of relative anemia in children with sickle cell disease in sub-Saharan Africa.

Science.gov (United States)

Bello-Manga, Halima; DeBaun, Michael R; Kassim, Adetola A

2016-11-01

Sickle cell disease (SCD) is the most common inherited hemoglobinopathy in the world, with the majority of cases in sub-Saharan Africa. Concomitant nutritional deficiencies, infections or exposure to environmental toxins exacerbate chronic anemia in children with SCD. The resulting relative anemia is associated with increased risk of strokes, poor cognitive function and impaired growth. It may also attenuate optimal response to hydroxyurea therapy, the only effective and practical treatment option for SCD in sub-Saharan Africa. This review will focus on the epidemiology, clinical sequelae, and treatment of relative anemia in children with SCD living in low and middle-income countries in sub-Saharan Africa. Areas covered: The causes and treatment of relative anemia in children with SCD in sub-Saharan Africa. The MEDLINE database was searched using medical subject headings (MeSH) and keywords for articles regarding relative anemia in children with SCD in sub-Saharan Africa. Expert commentary: Anemia due to nutritional deficiencies and infectious diseases such as helminthiasis and malaria are prevalent in sub-Saharan Africa. Their co-existence in children with SCD increases morbidity and mortality. Therefore, preventing, diagnosing and treating the underlying cause of this relative anemia will improve SCD-related outcomes in children in sub-Saharan Africa.

Double whammy- acute splenic sequestration crisis in patient with aplastic crisis due to acute parvovirus infection.

Science.gov (United States)

Minhas, Parminder S; K Virdi, Jaspreet; Patel, Rajeshkumar

2017-07-01

Splenic dysfunction is a major feature of sickle cell disease (SCD) and can manifest as acute splenic sequestration crisis (ASSC), which is the earliest life-threatening complication seen in patients with SCD. Aplastic crisis is another potentially deadly complication of sickle cell disease that develops when erythrocyte production temporarily drops. Infection with parvovirus B-19 frequently causes aplastic crises. These two complications are known to be mutually exclusive due to their classic presentation signs and symptoms but there have been few cases where a patient can have concomitant presentation of both phenomena, which can result in a fatal outcome. These few cases force us to rethink the etiology and subsequent management guidelines of these complications. We present to you a case of an unfortunate 23-year-old female who had both complications occurring at the same time, resulting in death.

Health policy for sickle cell disease in Africa: experience from Tanzania on interventions to reduce under-five mortality.

Science.gov (United States)

Makani, Julie; Soka, Deogratias; Rwezaula, Stella; Krag, Marlene; Mghamba, Janneth; Ramaiya, Kaushik; Cox, Sharon E; Grosse, Scott D

2015-02-01

Tanzania has made considerable progress towards reducing childhood mortality, achieving a 57% decrease between 1980 and 2011. This epidemiological transition will cause a reduction in the contribution of infectious diseases to childhood mortality and increase in contribution from non-communicable diseases (NCDs). Haemoglobinopathies are amongst the most common childhood NCDs, with sickle cell disease (SCD) being the commonest haemoglobinopathy in Africa. In Tanzania, 10,313 children with SCD under 5 years of age (U5) are estimated to die every year, contributing an estimated 7% of overall deaths in U5 children. Key policies that governments in Africa are able to implement would reduce mortality in SCD, focusing on newborn screening and comprehensive SCD care programmes. Such programmes would ensure that interventions such as prevention of infections using penicillin plus prompt diagnosis and treatment of complications are provided to all individuals with SCD. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

Integrating Interactive Web-Based Technology to Assess Adherence and Clinical Outcomes in Pediatric Sickle Cell Disease

Directory of Open Access Journals (Sweden)

Lori E. Crosby

2012-01-01

Full Text Available Research indicates that the quality of the adherence assessment is one of the best predictors for improving clinical outcomes. Newer technologies represent an opportunity for developing high quality standardized assessments to assess clinical outcomes such as patient experience of care but have not been tested systematically in pediatric sickle cell disease (SCD. The goal of the current study was to pilot an interactive web-based tool, the Take-Charge Program, to assess adherence to clinic visits and hydroxyurea (HU, barriers to adherence, solutions to overcome these barriers, and clinical outcomes in 43 patients with SCD age 6–21 years. Results indicate that the web-based tool was successfully integrated into the clinical setting while maintaining high patient satisfaction (>90%. The tool provided data consistent with the medical record, staff report, and/or clinical lab data. Participants reported that forgetting and transportation were major barriers for adherence to both clinic attendance and HU. A greater number of self-reported barriers (P<.01 and older age (P<.05 were associated with poorer clinic attendance and HU adherence. In summary, the tool represents an innovative approach to integrate newer technology to assess adherence and clinical outcomes for pediatric patients with SCD.

Sickle cell disease in Madhya Pradesh, Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals.

Science.gov (United States)

Yadav, Rajiv; Lazarus, Monica; Ghanghoria, Pawan; Singh, Mpss; Gupta, Rasik Behari; Kumar, Surendra; Sharma, Ravendra K; Shanmugam, Rajasubramaniam

2016-10-01

The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India. Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients. Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India. The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.

Autopsy findings and pattern of mortality in Nigerian sickle cell ...

African Journals Online (AJOL)

Introduction: Sickle Cell Disease (SCD) has a high mortality rate in the environment where we practice. There is lack of contemporal autopsy studies describing causes of death among SCD patients at our centre. Methods: This is a retrospective study of SCD patients who died between January 1991 and December 2008 ...

Increased concentrations of soluble CD40 ligand platelet in patients with primary antiphospholipidic syndrome.

Science.gov (United States)

Galicia López, Aida; Olguín Ortega, Lourdes; Saavedra, Miguel A; Méndez Cruz, René; Jimenez Flores, Rafael; García de la Peña, Maximiliano

2013-01-01

To determine the concentrations of sCD40L in patients with PAPS, and establish its association with the number of thrombosis. We included patients with PAPS and healthy controls of the same age and sex. For analysis, patients with PAPS were divided into 2 groups: 1) patients with 1 thrombosis, and 2) patients with >1 thrombosis. Soluble CD40L concentrations were determined by ELISA method. sCD40L concentrations were significantly higher in patients with PAPS compared with the controls (9.72 ng ± 11.23 ng/ml vs. 4.69 ± 4.04 ng/ml) (P=.04) There was no association between serum levels of sCD40L and the number of thrombosis (1 thrombosis: 9.81 ± 9.87 ng/ml vs 9.63 ± 12.75 ng/ml in ≥ 1thrombosis (P=.13). In women with pregnancy and abortions, (13 patients) concentrations of sCD40L were higher than in those patients without a history of abortion (26 patients) but without statically significant difference (12.11 ± 16.46 ng/ml vs. 8.80 ± 8.61 ng/ml) (P=.33). There was no correlation between levels of sCD40L and the total number of thrombosis. Patients with PAPS have higher concentrations of sCD40L compared with healthy subjects, although this is not associated with a greater number of thrombosis. Among patients with PAPS, there is a tendency to higher concentrations of sCD40L in women with pregnancy and history of abortion. Since the platelet is the main cellular source of sCD40L, is possible that this pathway plays a pathogenic role in patients with PAPS. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Perceived injustice predicts stress and pain in adults with sickle cell disease.

Science.gov (United States)

Ezenwa, Miriam O; Molokie, Robert E; Wilkie, Diana J; Suarez, Marie L; Yao, Yingwei

2015-06-01

Research evidence shows that perceived injustice is a context-based unfair treatment that has negative influence on health outcomes. We examined the contribution of patients' perceived injustice regarding interactions with health care providers to stress and pain in adults with sickle cell disease (SCD). This study was a cross-sectional correlational pilot study. Included in the study were adults with SCD who received their care from a university-affiliated comprehensive sickle cell clinic. Participants were 52 adults whose mean age was 34 ± 11 years (minimum [min] 20 years, maximum [max] 70 years). Most of the patients were African American (n = 48, 92%) and female (n = 41, 79%). Forty-eight patients (92%) reported having a high school diploma or higher. Participants completed the perceived injustice questionnaire, perceived stress questionnaire, and the PAINReportIt, which includes questions to measure pain and demographics. We analyzed the data using the linear regression analyses. Perceived injustice from doctors was a significant predictor of perceived stress (p pain (p = .002). Perceived injustice from nurses also was a significant predictor of perceived stress (p pain (p = .02). The procedural, distributive, and informational domains of perceived injustice attributed to both doctors and nurses consistently predicted patients' perceived stress, but only the procedural and distributive domains of perceived injustice consistently predicted patients' pain. Findings suggest that perceived injustice was negatively associated with stress and pain in adults with SCD and warrant further investigation in a larger sample. Published by Elsevier Inc.

Otoacoustic emission testing in Ghanaian children with sickle-cell disease.

Science.gov (United States)

Kegele, Josua; Hurth, Helene; Lackner, Peter; Enimil, Anthony; Sylverkin, Justice; Ansong, Daniel; Nkyi, Clara; Bonsu, Benedicta; Agbenyega, Tsiri; Schartinger, Volker H; Schmutzhard, Erich; Zorowka, Patrick; Kremsner, Peter; Schmutzhard, Joachim

2015-09-01

To evaluate hearing loss in children as a complication of sickle-cell disease. In Kumasi, Ghana, 35 children with SCD aged 6 months to 10 years underwent transient-evoked otoacoustic emissions testing (TEOAE) to investigate the function of the inner ear. Healthy Ghanaian children recruited in school and kindergarten served as controls. One of 35 children with SCD and 13 of 115 control children failed the otoacoustic emissions testing. This difference between the control group and the children with SCD was not statistically significant. Early hearing impairment does not regularly occur in sickle-cell disease, and in children, it is not a likely cause of delayed or impaired language development. © 2015 John Wiley & Sons Ltd.

Soluble CD163 levels in children with sickle cell disease

DEFF Research Database (Denmark)

Møller, Holger Jon; Nielsen, Marianne Jensby; Bartram, Jack

2011-01-01

Sickle cell disease (SCD) is characterized by vasculopathy, which has been causally linked to intravascular haemolysis and high levels of free plasma haemoglobin. Soluble CD163 (sCD163) is implicated in the clearance of free plasma haemoglobin and high plasma concentrations have been linked to ar...

Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

OpenAIRE

Smith, Kelsey E.; Schatz, Jeffrey

2016-01-01

Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship betwee...

Parental Problem-Solving Abilities and the Association of Sickle Cell Disease Complications with Health-related Quality of Life for School-age Children

Science.gov (United States)

Barakat, Lamia P.; Daniel, Lauren C.; Smith, Kelsey; Robinson, M. Renée; Patterson, Chavis A.

2013-01-01

Children with sickle cell disease (SCD) are at risk for poor health-related quality of life (HRQOL). The current analysis sought to explore parent problem-solving abilities/skills as a moderator between SCD complications and HRQOL to evaluate applicability to pediatric SCD. At baseline, 83 children ages 6–12 years and their primary caregiver completed measures of the child HRQOL. Primary caregivers also completed a measure of social problem-solving. A SCD complications score was computed from medical record review. Parent problem-solving abilities significantly moderated the association of SCD complications with child self-report psychosocial HRQOL (p = .006). SCD complications had a direct effect on parent proxy physical and psychosocial child HRQOL. Enhancing parent problem-solving abilities may be one approach to improve HRQOL for children with high SCD complications; however, modification of parent perceptions of HRQOL may require direct intervention to improve knowledge and skills involved in disease management. PMID:24222378

Soluble CD30 in patients with antibody-mediated rejection of the kidney allograft.

Science.gov (United States)

Slavcev, Antonij; Honsova, Eva; Lodererova, Alena; Pavlova, Yelena; Sajdlova, Helena; Vitko, Stefan; Skibova, Jelena; Striz, Ilja; Viklicky, Ondrej

2007-07-01

The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration. The median concentrations of the sCD30 molecule were identical in C4d-positive and C4d-negative patients before and after transplantation (65.5 vs. 65.0 and 28.2 vs. 36.0 U/ml, respectively). C4d+ patients who developed DSA de novo had a tendency to have higher sCD30 levels before transplantation (80.7+/-53.6 U/ml, n=8) compared with C4d-negative patients (65.0+/-33.4 U/ml, n=15). Soluble CD30 levels were evaluated as positive and negative (>or=100 U/ml and sCD30 estimation with regard to finding C4d deposits in peritubular capillaries were determined. The sensitivity of sCD30+ testing was generally below 40%, while the specificity of the test, i.e. the likelihood that if sCD30 testing is negative, C4d deposits would be absent, was 82%. C4d+ patients who developed DSA de novo were evaluated separately; the specificity of sCD30 testing for the incidence of HR in this cohort was 86%. We could not confirm in our study that high sCD30 levels (>or=100 U/ml) might be predictive for the incidence of HR. Negative sCD30 values might be however helpful for identifying patients with a low risk for development of DSA and antibody-mediated rejection.

Soluble CD163 predicts incident chronic lung, kidney and liver disease in HIV infection

DEFF Research Database (Denmark)

Kirkegaard-Klitbo, Ditte M; Mejer, Niels; Knudsen, Troels B

2017-01-01

OBJECTIVE: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma-soluble CD163 (sCD163) and incident non-AIDS comorbidities in well treated HIV-infected individuals. DESIGN: Prospective single...... was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. RESULTS: In HIV-1-infected individuals (n = 799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease [adjusted hazard ratio (aHR), 3.2; 95% confidence interval (CI): 1.34; 7.......46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer...

Effect of polymorphisms in the ABCG2, LEPR and SCD1 genes on ...

African Journals Online (AJOL)

Sahand Rayaneh

2016-06-24

Jun 24, 2016 ... Abstract. This study was performed to investigate the association between polymorphisms in the ABCG2 (ATP- binding cassette sub-family G member 2), LEPR (leptin receptor) and SCD1 (stearoyl-coenzyme A desaturase 1) genes and milk production traits in Holstein dairy cows in Iran. The analysis was ...

Soluble CD30 concentrations in ESRD patients with and without panel reactive HLA antibodies.

Science.gov (United States)

Vaidya, Smita; Partlow, David; Barnes, Titus; Thomas, Phillip; Gugliuzza, Kristin

2006-01-01

In this retrospective study we compared accuracy of panel reactive antibodies (PRA) with serum soluble CD30 (sCD30) contents in predicting acute rejection crisis post-renal transplant. Pre-transplant sera from 115 patients were evaluated for their PRA and sCD30 concentrations. All patients received calcineurin inhibitor-based immunosuppressive therapy. Objective measurements for rejection were biopsy-proven acute rejection (AR) episodes within first six months of the transplant. Post-transplant sera of patients with AR were tested for the presence of donor-specific HLA antibodies (DSA). Overall AR rate was 16% (18/115). Patients positive for PRA and sCD30 tests were at significantly higher risk for AVR compared with those patients negative for both the tests (36% vs. 5%, p=0.01). Among negative PRA patients risk for AR was significantly elevated if they were also tested positive for sCD30 concentrations (21% vs. 5%, p=0.04). Of the 18 patients with AR, 14 were positive for sCD30, and 13 of them (93%) developed DSA post-transplant (p=0.001). These data showed that patients positive for sCD30 contents are at high risk for the development of DSA and AR post-transplant regardless of their pre-transplant PRA.

Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice.

Science.gov (United States)

Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T; Hillery, Cheryl A; Pritchard, Kirkwood A

2013-11-01

Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO₂Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD.

Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

Science.gov (United States)

Veber, Daniela; Scalabrino, Giuseppe

2015-12-15

We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter. Copyright © 2015 Elsevier B.V. All rights reserved.

Soluble CD44 concentration in the serum and peritoneal fluid samples of patients with different stages of endometriosis.

Science.gov (United States)

Mashayekhi, Farhad; Aryaee, Hadis; Mirzajani, Ebrahim; Yasin, Ashraf Ale; Fathi, Abdolsatar

2015-09-01

Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity, most commonly implanted over visceral and peritoneal surface within the female pelvis. CD44 is a membrane protein expressed by human endometrial cells, and it has been shown to promote the adhesion of endometrial cells. The aim of this study was to determine the levels of soluble CD44 (sCD44) in the serum and peritoneal fluid (PF) samples of patients with different stages of endometriosis. 39 PF and serum samples from normal healthy and 130 samples from different stages of patients with endometriosis (33 cases of stage I, 38 stage II, 30 stage III and 29 stage IV) were included in this study. Total protein concentration (TPC) and the level of s-cMet in the serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay, respectively. No significant change in the TPC was seen in the serum of patients with endometriosis when compared to normal controls. Results obtained demonstrated that all serum and peritoneal fluid samples, presented sCD44 expression, whereas, starting from stages I to IV endometriosis, a significant increase of sCD44 expression was observed as compared to control group. The results of this study show that a high expression of sCD44 is correlated with advanced stages of endometriosis. It is also concluded that the detection of serum and/or peritoneal fluid sCD44 may be useful in classifying endometriosis.

Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

DEFF Research Database (Denmark)

Knøsgaard, L; Thomsen, S B; Støckel, M

2014-01-01

BACKGROUND: The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to s......-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model...

Delayed hemolytic transfusion reaction/hyperhemolysis syndrome in children with sickle cell disease.

Science.gov (United States)

Talano, Julie-An M; Hillery, Cheryl A; Gottschall, Jerome L; Baylerian, Diane M; Scott, J Paul

2003-06-01

Alloimmunization in patients with sickle cell disease (SCD) has a reported incidence of 5% to 36%. One complication of alloimmunization is delayed hemolytic transfusion reaction/hyperhemolysis (DHTR/H) syndrome, which has a reported incidence of 11%. In patients with SCD, clinical findings in DHTR/H syndrome occur approximately 1 week after the red blood cell (RBC) transfusion and include the onset of increased hemolysis associated with pain and profound anemia. The hemoglobin (Hb) often drops below pretransfusion levels. In many reported adult cases, the direct antiglobulin test (DAT) remains negative and no new alloantibody is detected as the cause for these transfusion reactions. To date, few pediatric cases have been reported with this phenomenon. The objective of this study was to describe the clinical and laboratory findings of a case series in children who had SCD and experienced a DHTR/H syndrome at our institution. An 11-year retrospective chart review of patients with discharge diagnosis of SCD and transfusion reaction was performed. DHTR/H syndrome was defined as the abrupt onset of signs and symptoms of accelerated hemolysis evidenced by an unexplained fall in Hb, elevated lactic dehydrogenase, elevated bilirubin above baseline, and hemoglobinuria, all occurring between 4 and 10 days after an RBC transfusion. Patient characteristics, time from transfusion, symptoms, reported DAT, new autoantibody or alloantibody formation, laboratory abnormalities, and complications were recorded. Patients with acute transfusion reactions were excluded. We encountered 7 patients who developed 9 episodes of DHTR/H syndrome occurring 6 to 10 days after RBC transfusion. Each presented with fever and hemoglobinuria. All but 1 patient experienced pain initially ascribed to vaso-occlusive crisis. The DAT was positive in only 2 of the 9 episodes. The presenting Hb was lower than pretransfusion levels in 8 of the 9 events. Severe complications were observed after the onset of

Non-traumatic spontaneous acute epidural hematoma in a patient with sickle cell disease.

Science.gov (United States)

Serarslan, Yurdal; Aras, Mustafa; Altaş, Murat; Kaya, Hasan; Urfalı, Boran

2014-01-01

A 19-year-old female with sickle cell anemia (SCD) was referred to our hospital after two days of hospitalization at another hospital for a headache crisis. This headache crisis was due to a raised intracranial pressure; these symptoms were noted and included in her comprehensive list of symptoms. There was an acute drop in the hemoglobin and hematocrit levels. The cranial CT scan demonstrated a left fronto-parietal acute epidural hematoma (AEH) and a calvarial bone expansion, which was suggestive of medullary hematopoiesis. The patient underwent emergent craniotomy and evacuation of the hematoma. There were no abnormal findings intra-operatively apart from the AEH, except skull thickening and active petechial bleeding from the dural arteries. Repeated CT scan showed a complete evacuation of the hematoma. The possible underlying pathophysiological mechanisms were discussed. In addition to the factors mentioned in the relevant literature, any active petechial bleeding from the dural arteries on the separated surface of the dura from the skull could have contributed to the expanding of the AEH in our patient. Neurosurgeons and other health care providers should be aware of spontaneous AEH in patients with SCD. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Vitamin D, d-dimer, Interferon γ, and sCD14 Levels are Independently Associated with Immune Reconstitution Inflammatory Syndrome: A Prospective, International Study

Directory of Open Access Journals (Sweden)

Laura W. Musselwhite

2016-02-01

Full Text Available To determine the immunological profile most important for IRIS prediction, we evaluated 20 baseline plasma biomarkers in Acquired Immunodeficiency Syndrome (AIDS patients initiating antiretroviral therapy (ART. Patients were enrolled in a randomized, placebo-controlled ART initiation trial in South Africa and Mexico to test whether maraviroc could prevent IRIS. Participants were classified prospectively as having IRIS within 6 months of ART initiation. Twenty plasma biomarkers were measured at study enrollment for 267 participants. Biomarkers were tested for predicting IRIS with adjustment for covariates chosen through forward stepwise selection. Sixty-two participants developed IRIS and of these 19 were tuberculosis (TB-IRIS. Baseline levels of vitamin D and higher d-dimer, interferon gamma (IFNγ, and sCD14 were independently associated with risk of IRIS in multivariate analyses. TB-IRIS cases exhibited a distinct biosignature from IRIS related to other pathogens, with increased levels of C-reactive protein (CRP, sCD14, IFNγ, and lower levels of Hb that could be captured by a composite risk score. Elevated markers of Type 1 T helper (Th1 response, monocyte activation, coagulation and low vitamin D were independently associated with IRIS risk. Interventions that decrease immune activation and increase vitamin D levels warrant further study.

Urinary Soluble CD163 in Active Renal Vasculitis.

Science.gov (United States)

O'Reilly, Vincent P; Wong, Limy; Kennedy, Claire; Elliot, Louise A; O'Meachair, Shane; Coughlan, Alice Marie; O'Brien, Eoin C; Ryan, Michelle M; Sandoval, Diego; Connolly, Emma; Dekkema, Gerjan J; Lau, Jiaying; Abdulahad, Wayel H; Sanders, Jan-Stephan F; Heeringa, Peter; Buckley, Colm; O'Brien, Cathal; Finn, Stephen; Cohen, Clemens D; Lindemeyer, Maja T; Hickey, Fionnuala B; O'Hara, Paul V; Feighery, Conleth; Moran, Sarah M; Mellotte, George; Clarkson, Michael R; Dorman, Anthony J; Murray, Patrick T; Little, Mark A

2016-09-01

A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis. Moreover, microdissected glomeruli from patients with small vessel vasculitis (SVV) had markedly higher levels of CD163 mRNA than did those from patients with lupus nephritis, diabetic nephropathy, or nephrotic syndrome. Both glomeruli and interstitium of patients with SVV strongly expressed CD163 protein. In 479 individuals, including patients with SVV, disease controls, and healthy controls, serum levels of sCD163 did not differ between the groups. However, in an inception cohort, including 177 patients with SVV, patients with active renal vasculitis had markedly higher urinary sCD163 levels than did patients in remission, disease controls, or healthy controls. Analyses in both internal and external validation cohorts confirmed these results. Setting a derived optimum cutoff for urinary sCD163 of 0.3 ng/mmol creatinine for detection of active renal vasculitis resulted in a sensitivity of 83%, specificity of 96%, and a positive likelihood ratio of 20.8. These data indicate that urinary sCD163 level associates very tightly with active renal vasculitis, and assessing this level may be a noninvasive method for diagnosing renal flare in the setting of a known diagnosis of SVV. Copyright © 2016 by the American Society of Nephrology.

Clinical events in a large prospective cohort of children with sickle cell disease in Nagpur, India: evidence against a milder clinical phenotype in India.

Science.gov (United States)

Jain, Dipty; Arjunan, Aishwarya; Sarathi, Vijaya; Jain, Harshwardhan; Bhandarwar, Amol; Vuga, Marike; Krishnamurti, Lakshmanan

2016-10-01

The clinical phenotype of sickle cell disease (SCD) has been reported to be milder in India than in the United States. The objective of this large single-center study was to examine the rate of complications to define the phenotype of SCD in India. The rate of complications per 100 person-years in 833 pediatric SCD patients for 1954 person-years in Nagpur, India including those diagnosed on newborn screen (NBS) and those presenting later in childhood (non-NBS) was compared to those reported in the cooperative study of sickle cell disease (CSSCD). Event rates were also compared between patients belonging to scheduled castes (SCs), scheduled tribes (STs), and other backward classes (OBC). Comparison of CSSCD versus Nagpur NBS versus Nagpur non-NBS for rates of pain (32.4 vs. 85.2 vs. 62.4), severe anemia (7.1 vs. 27 vs. 6.6), stroke (0.7 vs. 0.8 vs. 1.4), splenic sequestration (3.4 vs. 6.7 vs. 1.6), acute chest syndrome (24.5 vs. 23.6 vs. 1.0), and meningitis (0.8 vs. 0 vs. 0.1) revealed more frequent complications in Nagpur compared to CSSCD. Comparison of ST, SC, and OBC for rates of pain (84.6 vs. 71.9 vs. 63.5), acute chest syndrome (3.6 vs. 2.8 vs. 2.2), severe anemia (5.4 vs. 9.5 vs. 11.4), stroke (1.2 vs. 0.4 vs. 0.3), splenic sequestration (0.6 vs. 2.4 vs. 1.9), and meningitis (0.8 vs. 0 vs. 0.1) revealed significantly more frequent complications among ST. SCD-related complications are more frequent in Indian children than that observed in CSSCD. Further study is indicated to define SCD phenotype in India. © 2016 Wiley Periodicals, Inc.

Ankylosis of the hips and knees due to sickle cell disease [v1; ref status: indexed, http://f1000r.es/S7w2Gz

Directory of Open Access Journals (Sweden)

Saad Saleh Abdullah Al Elayan

2012-10-01

Full Text Available This is a case report of a 29-year-old Saudi male with sickle cell disease (SCD with severe stiffness of his joints, mainly both knees and hips, secondary to complications of SCD. He was severely crippled: unable to sit, stand or walk, and was bedridden for 8 years when he was presented to us. Radiographs showed fusion of both knees and hips. There was no evidence of active osteomyelitis by Gallium scan. The patient’s hemoglobin S decreased to levels below 30% by exchange transfusion. Bilateral total hip replacement, as well as unilateral total knee replacement, was carried out to improve his level of function. There is only one reported case of such severe and multiple joint complications in a single patient suffering from SCD. The increased life expectancy that medical advances have offered to the sickle-cell patients has led to the appearance of sickle-cell-related complications, which were previously only seen rarely. These complications were successfully managed and the patient was able to move and transfer using a wheel chair.

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

Science.gov (United States)

Colombatti, Raffaella; Palazzi, Giovanni; Masera, Nicoletta; Notarangelo, Lucia Dora; Bonetti, Elisa; Samperi, Piera; Barone, Angelica; Perrotta, Silverio; Facchini, Elena; Miano, Maurizio; Del Vecchio, Giovanni Carlo; Guerzoni, Maria Elena; Corti, Paola; Menzato, Federica; Cesaro, Simone; Casale, Maddalena; Rigano, Paolo; Forni, Gian Luca; Russo, Giovanna; Sainati, Laura

2018-02-01

The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sβ°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sβ° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5 g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5 mg/kg, and dose at full regimen was 17.1 mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sβ° patients. Only 10% started HU before 3 years. In 92%, 500 mg capsule was used; in 6%, the galenic was used; and in 2%, 100 mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sβ° patients and a trend toward improvement for SC/Sß+ patients was also observed. HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants. © 2017 Wiley Periodicals, Inc.

Soluble CD52 is an indicator of disease activity in chronic lymphocytic leukemia

NARCIS (Netherlands)

Vojdeman, Fie J.; Herman, Sarah E. M.; Kirkby, Nikolai; Wiestner, Adrian; van T' Veer, Mars B.; Tjønnfjord, Geir E.; Itälä-Remes, Maija A.; Kimby, Eva; Farooqui, Mohammed Z.; Polliack, Aaron; Wu, Ka Lung; Doorduijn, Jeanette K.; Alemayehu, Wendimagegn G.; Wittebol, Shulamiet; Kozak, Tomas; Walewski, Jan; Abrahamse-Testroote, Martine C. J.; van Oers, Marinus H. J.; Geisler, Christian H.; Niemann, Carsten U.

2017-01-01

CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early'

Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease.

Science.gov (United States)

Worrall, Douglas; Smith-Whitley, Kim; Wells, Lawrence

2016-03-01

Femoral head osteonecrosis (ON) secondary to sickle cell disease (SCD) often progresses to femoral head collapse, requiring total hip arthroplasty. However, this treatment has a limited durability and patients with SCD have higher rates of complications, requiring multiple revision operations. Identifying risk factors linked to ON in SCD can facilitate earlier precollapse diagnosis and surgical treatment aimed at preservation of the native hip joint. Fifty-nine children treated at our institution between January 2001 and April 2012 with SCD and ON, as diagnosed by magnetic resonance imaging or radiographic imaging, were compared with age-matched and sickle cell phenotype-matched (SS, SC, Sβ, Sβ) controls with no evidence of ON. Two sided t-tests assuming unequal variances determined statistically risk factors and threshold values were assigned to calculate odds ratios. Systolic blood pressure (P=1.2×10, OR=3.68), diastolic blood pressure (P=0.0084, OR=1.41), weight in the SCD-SS population (P=0.04, OR=1.85), and hemoglobin (Hb) in the SCD-SS population (P=0.036, OR=2.56) were elevated in cases. Curiously, dividing the Hb by the hematocrit to serve as a clinical proxy for the mean corpuscular Hb concentration (MCHC) produced an excellent predictor of ON (P=2.06×10, OR=5.17), which was especially pronounced in the SCD-SS subpopulation (P=2.28×10, OR=8.65). Among children with SCD, the overall prevalence of ON was 9% (59/658) and the phenotype with the highest prevalence of ON was Sβ thalassemia with an ON prevalence of 11.1%. There was no observed correlation between ON and height, body mass index, cholesterol, mean corpuscular volume, hematocrit, or glucocorticoid use. These data support a novel clinical marker, the MCHC proxy, as the strongest predictor of ON in children with SCD. High-risk children should receive hip magnetic resonance imaging to diagnose early ON and facilitate interventions focused on hip preservation, forestalling, or possibly preventing

Extramedullary hematopoiesis of the liver in a child with sickle cell disease: A rare complication.

Science.gov (United States)

Barrier, Angela; Willy, Simo; Slone, Jeremy S

2015-08-01

We present the case of a 7-year-old Cameroonian girl with sickle cell disease (SCD) who presented with progressive abdominal distension, fever, severe anemia, respiratory distress, and fatigue. Abdominal ultrasound showed a 15.3 cm × 11.5 cm × 15.5 cm solid echogenic mass within the left lobe of the liver. Fine-needle aspiration showed features of extramedullary hematopoiesis (EMH). Despite transfusions, antibiotics, and initiation of hydroxyurea the patient died of respiratory failure during the hospital stay. There is a paucity of information on EMH in the pediatric sickle cell population, especially from resource-limited settings such as western Africa. EMH, however, is a known complication of SCD and should be considered in patients presenting with mass lesions in the setting of chronic anemia. With limited therapeutic interventions for EMH, including radiation and hydroxyurea, the emphasis should be on improving overall treatment of patients with chronic and untreated hemolytic anemia, especially in low-income countries. © 2015 Japan Pediatric Society.

Soluble CD30 and Cd27 levels in patients undergoing HLA antibody-incompatible renal transplantation.

Science.gov (United States)

Hamer, Rizwan; Roche, Laura; Smillie, David; Harmer, Andrea; Mitchell, Daniel; Molostvov, Guerman; Lam, For T; Kashi, Habib; Tan, Lam Chin; Imray, Chris; Fletcher, Simon; Briggs, David; Lowe, David; Zehnder, Daniel; Higgins, Rob

2010-08-01

HLA antibody-incompatible transplantation has a higher risk of rejection when compared to standard renal transplantation. Soluble CD30 (sCD30) has been shown in many, but not all, studies to be a biomarker for risk of rejection in standard renal transplant recipients. We sought to define the value of sCD30 and soluble CD27 (sCD27) in patients receiving HLA antibody-incompatible transplants. Serum taken at different time points from 32 HLA antibody-incompatible transplant recipients was retrospectively assessed for sCD30 and sCD27 levels by enzyme-linked immunosorbent assay (ELISA). This was compared to episodes of acute rejection, post-transplant donor-specific antibody (DSA) levels and 12 month serum creatinine levels. No association was found between sCD27 and sCD30 levels and risk of acute rejection or DSA levels. Higher sCD30 levels at 4-6 weeks post-transplantation were associated with a higher serum creatinine at 12 months. Conclusion patients undergoing HLA antibody-incompatible transplantation are at a high risk of rejection but neither sCD30 (unlike in standard transplantation) nor sCD27 was found to be a risk factor. High sCD30 levels measured at 4-6 weeks post-transplantation was associated with poorer graft function at one year. Copyright © 2010 Elsevier B.V. All rights reserved.

Symptoms of Depression and Anxiety in Adolescents with Sickle Cell Disease: The Role of Intrapersonal Characteristics and Stress Processing Variables

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Simon, Katherine; Barakat, Lamia P.; Patterson, Chavis A.; Dampier, Carlton

2009-01-01

Sickle cell disease (SCD) complications place patients at risk for poor psychosocial adaptation, including depression and anxiety symptoms. This study aimed to test a mediator model based on the Risk and Resistance model to explore the role of intrapersonal characteristics and stress processing variables in psychosocial functioning. Participants…

Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

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Hildenbrand, Aimee K; Nicholls, Elizabeth G; Daly, Brian P; Marsac, Meghan L; Tarazi, Reem; Deepti, Raybagkar

2014-03-01

For children with sickle cell disease (SCD), pain is associated with significant current and future morbidity and mortality. Unfortunately, few evidence-based guidelines exist for the management of pain episodes in children with SCD. To inform empirically based treatment strategies for pain management in pediatric SCD, this review integrates and evaluates the extant literature on psychosocial and pharmacological approaches to the management of pain. Findings reveal a paucity of rigorous investigations of psychosocial and pharmacological pain management interventions in children with SCD. Psychosocial interventions included were primarily cognitive-behavioral in nature, whereas pharmacological approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone). However, to date there is not a "gold standard" for pain management among children with SCD. Because psychosocial and physiological processes each play a role in the etiology and experience of pain, effective pain management requires multidimensional, comprehensive treatment approaches. Considering the significant impact of pain on functional outcomes and quality of life among children with SCD, additional clinical trials are warranted to ensure that interventions are safe and efficacious.

Fertility challenges for women with sickle cell disease.

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Ghafuri, Djamila L; Stimpson, Sarah-Jo; Day, Melissa E; James, Andra; DeBaun, Michael R; Sharma, Deva

2017-10-01

Sickle cell disease (SCD) represents one of the most common monogenic blood disorders worldwide, with an incidence of over 300,000 newborns affected per year. Reproductive challenges for men and women with SCD have been previously reviewed; however, evidence-based strategies to prevent and manage infertility and increase fecundity are lacking in women with SCD, which is one of the most important factors for quality of life. Areas covered: This review article summarizes the known risk factors for infertility, low fecundity, and premature menopause related to SCD. Expert commentary: Women with SCD have unique risk factors that may impact their ability to conceive, including chronic inflammation, oxidative stress, transfusion-related hemochromatosis, and ovarian sickling, causing ischemia and reperfusion injury to the ovary. Contraception is strongly recommended while on hydroxyurea therapy during reproductive years and discontinuing hydroxyurea for family planning and during pregnancy based on teratogenicity in animal studies. Hematopoietic stem cell transplantation (HSCT), the only curative therapy, sometimes involves conditioning regimens containing alkylating agents and total body irradiation that contribute to infertility and premature ovarian failure. Prior to HSCT or gene therapy, we strongly recommend referral to a reproductive endocrinologist to discuss fertility preservation and surrogacy options for all women with SCD.

Socio-environmental exposures and health outcomes among persons with sickle cell disease.

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Monika R Asnani

Full Text Available There is much variability in the expression of sickle cell disease (SCD and recent works suggest that environmental and social factors may also influence this variability. This paper aims to use geographic information systems technology to examine the association between socio-environmental exposures and health outcomes in all persons who have attended or currently attend the Sickle Cell Unit in Jamaica. Rural patients presented for clinical care at older ages and had less annual visits to clinic. Persons travelled relatively long distances to seek SCD care and those travelling longer had less health maintenance visits. Urban patients had a higher prevalence of significant pain crises (69.4% vs. 55.8%, p value<0.001 and respiratory events (21.2% vs. 14%, p value<0.001. Prevalence of leg ulcers did not vary between rural and urban patients but was higher in males than in females. Females also had lower odds of having respiratory events but there was no sex difference in history of painful crises. Persons with more severe genotypes lived in higher poverty and travelled longer for healthcare services. Persons in areas with higher annual rainfall, higher mean temperatures and living farther from factories had less painful crises and respiratory events. The paper highlights a need for better access to healthcare services for Jamaicans with SCD especially in rural areas of the island. It also reports interesting associations between environmental climatic exposures and health outcomes.

Changes in urine albumin to creatinine ratio with the initiation of hydroxyurea therapy among children and adolescents with sickle cell disease.

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Tehseen, Sarah; Joiner, Clinton H; Lane, Peter A; Yee, Marianne E

2017-12-01

Renal damage is a progressive complication of sickle cell disease (SCD) that begins in childhood and may progress to renal failure and early mortality in 12% of adults with hemoglobin SS (HbSS) SCD. Early sickle nephropathy is characterized by hyperfiltration and microalbuminuria; therefore, urine albumin to creatinine ratio (ACR) is an effective screening tool for its detection. This study investigated the effect of hydroxyurea (HU) therapy on urine ACR levels among children with SCD. A retrospective review was conducted to identify all patients with HbSS or HbSβ 0 thalassemia of age 7-18 years who began HU therapy in 2011-2013; a control group of patients not on HU were matched by age and baseline hemoglobin. All urine ACR measurements ≤24 months prior to and ≥24 months after HU initiation were recorded. There were 63 eligible patients on HU and 13 (25%) with albuminuria prior to HU initiation. Among those with baseline albuminuria, the median ACR was 96 mg/g prior to HU, 39 mg/g at 1 year (P = 0.02), and 25 mg/g at 2 years (P = 0.03). Albuminuria normalized in 37.5% (6/16) after 1 year and 61% (8/13) after 2 years of HU therapy. Among those without albuminuria prior to HU, 13% (6/47) developed albuminuria during HU therapy. Sixteen percent (13/80) of control patients had albuminuria in the beginning of study period, which normalized in 15% (two of 13) of patients at 1-year follow up. Introduction of HU is associated with significant decreases in urine ACR in children with SCD and albuminuria. © 2017 Wiley Periodicals, Inc.

Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice1[S

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Zhang, Hao; Xu, Hao; Weihrauch, Dorothee; Jones, Deron W.; Jing, Xigang; Shi, Yang; Gourlay, David; Oldham, Keith T.; Hillery, Cheryl A.; Pritchard, Kirkwood A.

2013-01-01

Activated leukocytes and polymorphonuclear neutrophils (PMN) release myeloperoxidase (MPO), which binds to endothelial cells (EC), is translocated, and generates oxidants that scavenge nitric oxide (NO) and impair EC function. To determine whether MPO impairs EC function in sickle cell disease (SCD), control (AA) and SCD mice were treated with N-acetyl-lysyltyrosylcysteine-amide (KYC). SCD humans and mice have high plasma MPO and soluble L-selectin (sL-selectin). KYC had no effect on MPO but decreased plasma sL-selectin and malondialdehyde in SCD mice. MPO and 3-chlorotyrosine (3-ClTyr) were increased in SCD aortas. KYC decreased MPO and 3-ClTyr in SCD aortas to the levels in AA aortas. Vasodilatation in SCD mice was impaired. KYC increased vasodilatation in SCD mice more than 2-fold, to ∼60% of levels in AA mice. KYC inhibited MPO-dependent 3-ClTyr formation in EC proteins. SCD mice had high plasma alanine transaminase (ALT), which tended to decrease in KYC-treated SCD mice (P = 0.07). KYC increased MPO and XO/XDH and decreased 3-ClTyr and 3-nitrotyrosine (3-NO2Tyr) in SCD livers. These data support the hypothesis that SCD increases release of MPO, which generates oxidants that impair EC function and injure livers. Inhibiting MPO is an effective strategy for decreasing oxidative stress and liver injury and restoring EC function in SCD. PMID:23956444

Regression of electrocardiographic left ventricular hypertrophy during antihypertensive therapy and reduction in sudden cardiac death: the LIFE Study

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Wachtell, Kristian; Okin, Peter M; Olsen, Michael H

2007-01-01

BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction in Hypertens......BACKGROUND: Sudden cardiac death (SCD) occurs more often in patients with ECG left ventricular (LV) hypertrophy. However, whether LV hypertrophy regression is associated with a reduced risk of SCD remains unclear. METHODS AND RESULTS: The Losartan Intervention for End Point Reduction...... risk of SCD independently of treatment modality, blood pressure reduction, prevalent coronary heart disease, and other cardiovascular risk factors in hypertensive patients with LV hypertrophy. Udgivelsesdato: 2007-Aug-14...

Influence of immunosuppressive drugs on the CD30 molecule in kidney transplanted patients.

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Grenzi, Patricia Cristina; Campos, Érika Fernandes; Tedesco-Silva, Hélio; Felipe, Claudia Rosso; Soares, Maria Fernanda; Medina-Pestana, José; Hansen, Hinrich Peter; Gerbase-DeLima, Maria

2018-04-12

Soluble CD30 (sCD30) is a suggested marker for kidney transplantation outcomes. We investigated whether sCD30 serum levels are influenced by immunosuppression and whether they correlate with findings in protocol biopsies and with CD30 gene expression in peripheral blood mononuclear cells (PBMC). We studied 118 kidney transplant recipients that initially received tacrolimus (TAC) and, at month-3, were converted or not to sirolimus (SRL). sCD30 serum levels gradually declined after transplantation, being the decline more pronounced in the SRL group. CD30 gene expression in PBMC was higher in the SRL group than in the TAC group. Patients with IF/TA ≥ I in the month-24 protocol biopsy had higher sCD30 levels than patients without IF/TA, in the SRL group (P = .03) and in the TAC group (P = .07). CD30 + cells were observed in three out of 10 biopsies with inflammatory infiltrate from the SRL group. In mixed lymphocyte cultures, SRL and TAC diminished the number of CD30 + T cells and the sCD30 levels in the supernatant, but the effect of SRL was stronger. Overall, sCD30 levels are lower in SRL-treated patients, but the association between increased sCD30 levels and IF/TA at month-24 post-transplantation is stronger in SRL than in TAC-treated patients. Copyright © 2018 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Diagnostic value of soluble CD163 serum levels in patients suspected of meningitis: comparison with CRP and procalcitonin

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Knudsen, Troels Bygum; Larsen, Klaus; Kristiansen, Thomas Birk

2007-01-01

The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected of meningi......The aim of the study was to evaluate and compare the diagnostic value of sCD163 serum levels with CRP and PCT in meningitis and bacterial infection. An observational cohort study was conducted between February 2001 and February 2005. The study population comprised 55 patients suspected...... marker for distinguishing bacterial infection from non-bacterial disease (specificity 0.91; sensitivity 0.47). However, the overall diagnostic accuracy of CRP (AUC =0.91) and PCT (AUC =0.87) were superior (p... infection, the AUC of sCD163 (0.83) did not differ significantly from those of CRP or PCT. All markers had AUCs CRP and PCT had high diagnostic value and were superior as markers of bacterial infection compared to s...

Sickle cell disease in western Sudan: genetic epidemiology and predictors of knowledge attitude and practices.

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Daak, Ahmed A; Elsamani, Elfatih; Ali, Eltigani H; Mohamed, Fatma A; Abdel-Rahman, Manar E; Elderdery, Abozer Y; Talbot, Octavious; Kraft, Peter; Ghebremeskel, Kebreab; Elbashir, Mustafa I; Fawzi, Wafaie

2016-05-01

To investigate the epidemiology of sickle cell disease (SCD) and determinants of knowledge, attitudes and practices (KAP) towards SCD in western Kordofan State, Sudan. A community-based, descriptive, cross-sectional study was conducted in three towns. Three hundred and seventy-two households were polled, and blood samples for haemoglobin phenotyping were collected from 1116 individuals. Sociodemographic, socio-economic and KAP data were collected using investigator-administered questionnaires. Descriptive, frequency distribution and multiple regression analyses were performed. About 50.9% of the study population were Misseriya tribes. Consanguineous marriages were reported by 67.5% of the households. The highest percentage of homozygous SCD was 2.8% among children under 5 years of age. About 24.9% were carriers of HbS allele (HbAS). HbS allele frequency was highest in children aged 5-11 years (18.3%, CI: 13.7-22.9%) and lowest in males >15 years old (12.0%, CI: 6.1-17.9%). The average HbS frequency across all age groups was 14.5% (95% CI: 12.2-16.8%). The most frequent β-globin gene cluster haplotype was the Cameroon (30.8%), followed by the Benin (21.8%), the Senegal (12.8%) and the Bantu (2.2%) haplotypes. About 17.0% of all-cause child deaths were due to SCD. The estimated change in log odds of having the SS genotype per year increase in age was (-) 0.0058 (95% CI -0.0359, 0.0242). This represents a non-statistically significant 2.9% increase in 5-year mortality for individuals with the SS genotype relative to those with AS and AA genotypes. About 46.9% of the households had poor knowledge, 26.1% had satisfactory knowledge, and 26.9% had good knowledge about sickle cell disease. Mothers' and fathers' educational levels were significant predictors of good knowledge about SCD (P < 0.05). About 48.0% had a satisfactory attitude towards sickle cell disease while 30.7% had poor attitude and only 21.3 showed good attitudes. Poor knowledge about SCD and low socio

Sickle cell disease among children in Africa: An integrative literature review and global recommendations

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Lucky L. Mulumba

2015-01-01

There have been significant improvements in the morbidity and mortality rates for children with SCD in high resource countries such as the United States due to factors such as early diagnosis through newborn screening programs, prophylactic therapy, comprehensive care programs including hydroxyurea therapy, and bone marrow transplant. Many of these interventions can confer the same benefits to SCD patients in Africa. Newborn screening for SCD, developing partnerships between high resource countries and countries in Africa to support training of healthcare workers, research, and sharing of knowledge can help to reduce the SCD burden in Africa.

Renal Replacement Therapy in End-Stage Sickle Cell Nephropathy: Presentation of Two Cases and Literature Review

International Nuclear Information System (INIS)

Al-Mueilo, Samir H.

2005-01-01

Chronic renal failure develops in 4-18% of patients with sickle cell anemia. Hemodialysis and kidney transplant are viable options in the management of end-stage renal disease in patients with sickle cell diseases (SCD). Information on kidney disease among Saudi patients with SCD is non-existing. In this report, the clinical course of two adult males with end-stage sickle cell nephropathy from Eastern Saudi Arabia is described. Literature on renal replacement therapy in sickle cell anemia (SCA) is discussed. (author)

An analysis of the NIH-supported sickle cell disease research portfolio.

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Gavini, Nara; Hoots, W Keith; Mensah, George A; Hanspal, Manjit

2015-02-01

Sickle cell disease (SCD), an inherited blood disorder is due to a single amino acid substitution on the beta chain of hemoglobin, and is characterized by anemia, severe infections, acute and chronic pain, and multi-organ damage. The National Institutes of Health (NIH) is dedicated to support basic, translational and clinical science research to improve care and ultimately, to find a cure for SCD that causes such suffering. This report provides a detailed analysis of grants funded by the NIH for SCD research in Fiscal Years 2007 through 2013. During this period, the NIH supported 247 de novo grants totaling $272,210,367 that address various aspects of SCD. 83% of these funds supported research project grants investigating the following 5 scientific themes: Pathology of Sickle Red Blood Cells; Globin Gene Expression; Adhesion and Vascular Dysfunction; Neurological Complications and Organ-specific Dysfunction; and Pain Management and Intervention. The remaining 17% of total funds supported career development and training grants; Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants; large Center grants; and Conference grants. Further analysis showed that the National Heart, Lung, and Blood Institute (NHLBI) is the largest funder of SCD research within NIH with 67% of total grants, contributing 77% of total funds; followed by the National Institute for Digestive Diseases and Kidney (NIDDK) that is funding 19% of grants, contributing 13% of total funds. The remaining 14% of grants totaling 10% of the funds were supported by all other NIH Institutes/Centers (ICs) combined. In summary, the NIH is using multiple funding mechanisms to support a sickle cell disease research agenda that is intended to advance the detection, treatment, and cure of this debilitating genetic disease. Published by Elsevier Inc.

Emergency Department (ED, ED Observation, Day Hospital, and Hospital Admissions for Adults with Sickle Cell Disease

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Susan Silva

2018-02-01

Full Text Available Introduction: Use of alternative venues to manage uncomplicated vaso-occlusive crisis (VOC, such as a day hospital (DH or ED observation unit, for patients with sickle cell anemia, may significantly reduce admission rates, which may subsequently reduce 30-day readmission rates. Methods: In the context of a two-institution quality improvement project to implement best practices for management of patients with sickle cell disease (SCD VOC, we prospectively compared acute care encounters for utilization of 1 emergency department (ED; 2 ED observation unit; 3 DH, and 4 hospital admission, of two different patient cohorts with SCD presenting to our two study sites. Using a representative sample of patients from each institution, we also tabulated SCD patient visits or admissions to outside hospitals within 20 miles of the patients’ home institutions. Results: Over 30 months 427 patients (297 at Site 1 and 130 at Site 2 initiated 4,740 institutional visits, totaling 6,627 different acute care encounters, including combinations of encounters. The range of encounters varied from a low of 0 (203 of 500 patients [40.6%] at Site 1; 65 of 195 patients [33.3%] at Site 2, and a high of 152 (5/month acute care encounters for one patient at Site 2. Patients at Site 2 were more likely to be admitted to the hospital during the study period (88.4% vs. 74.4%, p=0.0011 and have an ED visit (96.9% vs. 85.5%, p=0.0002. DH was used more frequently at Site 1 (1.207 encounters for 297 patients at Site 1, vs. 199 encounters for 130 patients at Site 2, and ED observation was used at Site 1 only. Thirty-five percent of patients visited hospitals outside their home academic center. Conclusion: In this 30-month assessment of two sickle cell cohorts, healthcare utilization varied dramatically between individual patients. One cohort had more hospital admissions and ED encounters, while the other cohort had more day hospital encounters and used a sickle cell disease

Incidence of sickle cell disease and other hemoglobin variants in 10,095 Lebanese neonates.

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Evelyne Khoriaty

Full Text Available Hemoglobinopathies are highly prevalent diseases and impose a public health burden. Early diagnosis and treatment can ameliorate the course of these diseases and improve survival. Despite purported high incidence of hemoglobinopathies in Lebanon, there are no nationwide screening programs. In this study, newborn screening utilizing high pressure liquid chromatography was executed in all public hospitals across Lebanon between 2010 and 2013. All newborns with an abnormal hemoglobin (Hb were offered genetic counseling and all those with disease were enrolled in comprehensive hemoglobinopathy clinics. Among newborns, 2.1% were found to have an abnormal Hb variant with sickle Hb being the most common while 0.1% were found to have sickle cell disease (SCD. The majority of those with SCD had non-Lebanese origins. The most common causes of hospitalizations in infants with SCD were acute splenic sequestration and pain crises. No bacteremia or other life threatening infections were noted. At a median follow up 14 months (follow up range 7 to 34 months, all children with disease are alive and compliant with treatment. Systematic screening for SCD and other Hb variants was shown to be feasible, cost effective, and of accurate predictive value. This program was also clinically effective because it led to the identification of babies with disease and to providing them with free early multidisciplinary care. Conclusively, a newborn screening program should be implemented across Lebanon to detect hemoglobinopathies and initiate early therapeutic and preventive strategies and genetic counseling.

Progression and prognostic indicators of bronchial disease in children with sickle cell disease.

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Williams, Sophia N; Nussbaum, Eliezer; Yoonessi, Leila; Morphew, Tricia; Randhawa, Inderpal

2014-06-01

The pulmonary complications of sickle cell disease (SCD) are a leading cause of morbidity and mortality (MacLean et al. Am J Respir Crit Care Med 178:1055-1059, 2008; Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; National Heart, Lung, and Blood Institute, 2009). Despite this recognition, predictive markers of lung dysfunction progression remain elusive (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Platt et al. N Engl J Med 330:1639-1644, 1994; Caboot et al. Curr Opin Pediatr 20:279-287, 2008; Field et al. Am J Hematol 83:574-576, 2008; Shirlo et al. Peadiatr Respir Review 12:78-82, 2011). This study was designed describe the longitudinal progression and identify specific markers that influence bronchial disease in SCD. A retrospective, chart review of 89 patients with SCD was conducted. All patients underwent spirometry in conjunction with body plethysmography as part of routine care. Eleven lung function variables were assessed, five of which were selected to establish patterns of normal, obstructive, restrictive, or mixed obstructive-restrictive physiology (Klings et al. Am J Respir Crit Care Med 173:1264-1269, 2006; Field et al. Am J Hematol 83:574-576, 2008). In the unadjusted model, forced expiratory volume in one second (FEV1)% of predicted trended downward with age, while total lung capacity (TLC)% of predicted showed a bimodal distribution and carbon monoxide diffusion capacity corrected for hemoglobin (DLCOcor)% of predicted remained stable. Adjusting for acute chest syndrome (ACS) episodes, medication status, and growth velocity (GV), the final model demonstrated that the downward trend between FEV1% of predicted with age was further influenced by the latter two factors. Initial decline in FEV1% of predicted is associated with worsening pulmonary dysfunction over time. Independent of ACS episodes, the factors most influential on the progression of FEV1% predicted include the introduction of medications as well as the

Respect, trust, and the management of sickle cell disease pain in hospital: comparative analysis of concern-raising behaviors, preliminary model, and agenda for international collaborative research to inform practice

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Elander, James; Beach, Mary Catherine; Haywood, Carlton

2011-01-01

Background/objectives Qualitative interview studies suggest that adult patients’ experiences of hospital treatment for sickle cell disease (SCD) pain reflect an absence of respect by providers for patients, and an absence or breakdown of trust. Systematic comparisons between treatment settings could help identify contextual influences on respect and trust. Design Quantitative comparison of concern-raising behaviors (pain treatment outcomes indicating breakdowns of trust) among adult SCD patients in Baltimore, Maryland, USA, and London, UK, followed by analysis of potential explanations for differences, including socio-cultural and behavioral factors, with a preliminary model of the processes leading to concern-raising behaviors. Results Rates of concern-raising behaviors were significantly higher in Baltimore than London. The model identifies respect and trust as key factors which could be targeted in efforts to improve the quality of SCD pain management in hospital. Conclusion An agenda for international, interdisciplinary research to improve the treatment of SCD pain in hospital should include: comparative analyses between countries and treatment settings of factors that could influence respect and trust; research to test hypotheses derived from models about the roles of respect and trust in the treatment of pain; studies of the impact of healthcare structures and policy on patients’ experiences of care; research focusing on developmental and interpersonal processes related to respect and trust; applications of attribution and other social psychology theories; and development and evaluation of interventions to improve the hospital treatment of SCD pain by increasing respect and trust. PMID:21797726

Predictive value of elevated soluble CD40 ligand in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction.

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Pusuroglu, Hamdi; Akgul, Ozgur; Erturk, Mehmet; Uyarel, Huseyin; Bulut, Umit; Akkaya, Emre; Buturak, Ali; Surgit, Ozgur; Fuat, Ali; Cetin, Mustafa; Yldrm, Aydn

2014-11-01

The aim of this study was to evaluate the prognostic value of soluble CD40 ligand (sCD40L) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing a primary percutaneous coronary intervention (PCI). The prognostic value of sCD40L has been documented in patients with acute coronary syndrome; however, its value in acute STEMI remains unclear. We prospectively enrolled 499 consecutive STEMI patients (397 men, 102 women) undergoing primary PCI. The study population was divided into tertiles on the basis of admission sCD40L values. The high sCD40L group (n=168) included patients with a value in the third tertile (≥0.947 mg/l) and the low sCD40L group (n=331) included patients with a value in the lower two tertiles (0.947 mg/l) is a powerful independent predictor of 1-year all-cause mortality (odds ratio: 3.68; 95% confidence interval: 1.54-8.77; P=0.003). The results of this study suggest that a high sCD40L level at admission is associated with increased in-hospital and 1-year all-cause mortality rates in patients with STEMI undergoing primary PCI.

AETIOPATHOGENESIS OF FEVER IN HOSPITALISED SICKLE CELL DISEASE CHILDREN REVISITED WITH SPECIAL REFERENCE TO BLOOD CULTURE

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Sadhana Panda

2017-10-01

Full Text Available BACKGROUND Sickle Cell Disease (SCD poses a considerable health burden in India. The sickle gene is widespread among many tribal population groups in India with prevalence of heterozygotes varying from 1-40 percent. The disease has multiple acute and chronic complications, including haemolytic crises, severe pain, renal complications, thromboembolic phenomenon and overwhelming infections; some complications of SCD generate high mortality. MATERIALS AND METHODS This is a cross-sectional, hospital inpatient based, observational study. Convenience sampling technique was used to include 74 consecutively diagnosed cases of sickle cell disease children less than 14 years of age and suffering from fever. A blood culture was performed in each case prior to starting of antibiotics. RESULTS The present study comprised of 74 children with confirmed sickle cell disease admitted to ward with fever. The largest numbers of cases were between 1 to 3 years age group. Febrile episodes decreased as the age advanced. Around 30% of febrile patients presented with cough followed by 24% with pain in limbs. Anaemia was the most common physical finding (92% followed by splenomegaly in 86% cases. URTI being most common aetiology. Most common organism isolated by blood culture was Staph. aureus in 8 samples. CONCLUSION As because fever is a consistent finding in severe bacterial infections, extensive evaluation, early intervention in febrile SCD children may reduce the morbidity and mortality rates. Although, the greatest concern has traditionally been S. pneumoniae, effective vaccination has reduced its incidence. It is probably wise to treat all highly febrile children with sickle cell disease with antibiotics pending the results of blood culture. Strengthening of routine immunisation programme is needed.

Sickle Cell Disease

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... days. Your body may have trouble making enough new cells to replace the ones that you lost. Because ... Indian backgrounds. What are the symptoms of sickle cell disease? People with ... the whites of the eyes (icterus) The effects of SCD vary from person ...

Management of Sickle Cell Disease: A Review for Physician Education in Nigeria (Sub-Saharan Africa

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Ademola Samson Adewoyin

2015-01-01

Full Text Available Sickle cell disease (SCD predominates in sub-Saharan Africa, East Mediterranean areas, Middle East, and India. Nigeria, being the most populous black nation in the world, bears its greatest burden in sub-Saharan Africa. The last few decades have witnessed remarkable scientific progress in the understanding of the complex pathophysiology of the disease. Improved clinical insights have heralded development and establishment of disease modifying interventions such as chronic blood transfusions, hydroxyurea therapy, and haemopoietic stem cell transplantation. Coupled with parallel improvements in general supportive, symptomatic, and preventive measures, current evidence reveals remarkable appreciation in quality of life among affected individuals in developed nations. Currently, in Nigeria and other West African states, treatment and control of SCD are largely suboptimal. Improved knowledge regarding SCD phenotypes and its comprehensive care among Nigerian physicians will enhance quality of care for affected persons. This paper therefore provides a review on the aetiopathogenesis, clinical manifestations, and management of SCD in Nigeria, with a focus on its local patterns and peculiarities. Established treatment guidelines as appropriate in the Nigerian setting are proffered, as well as recommendations for improving care of affected persons.

Genetic determinants and stroke in children with sickle cell disease,

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Daniela O.W. Rodrigues

Full Text Available Abstract Objective: To verify genetic determinants associated with stroke in children with sickle cell disease (SCD. Methods: Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal, haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA, using the chi-squared test in the program SPSS® version 14.0. Results: Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p = 0.001 and males (24.1% vs. 9.6%; p = 0.044. The presence of α-thal (p = 0.196, the CAR haplotype (p = 0.543, and socioeconomic factors were not statistically significant in association with the occurrence of stroke. Conclusion: There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

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Karahan, Gonca E; Caliskan, Yasar; Ozdilli, Kursat; Kekik, Cigdem; Bakkaloglu, Huseyin; Caliskan, Bahar; Turkmen, Aydin; Sever, Mehmet S; Oguz, Fatma S

2017-01-13

Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

Child-rearing practices of primary caregivers of children with sickle cell disease: the perspective of professionals and caregivers.

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Noll, R B; McKellop, J M; Vannatta, K; Kalinyak, K

1998-04-01

To obtain caregiver and medical professional opinions regarding the child-rearing practices of caregivers of children with sickle cell diseases (SCD). We obtained self-reports of parenting practices from 48 caregivers of children with SCD and 48 caregivers of matched classroom comparison peers using the Child-Rearing Practices Report (CRPR). CRPR ratings were also obtained from 12 experts in pediatric SCD regarding their predictions of how a parent of a child with SCD would respond. The experts predicted differences in protectiveness, discipline, and excessive worry. Objective interim and lifetime illness severity scores were obtained for the children with SCD. Caregivers showed similarity between the two groups, disagreement with the experts, and minimal relationship to illness severity. Experts who work with children with chronic illnesses such as SCD seem to have stereotyped ideas that do not correspond with parental reports of their child-rearing practices, suggesting the need for careful clinical evaluations.

Gastrointestinal and hepatic complications of sickle cell disease.

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Ebert, Ellen C; Nagar, Michael; Hagspiel, Klaus D

2010-06-01

Sickle cell disease (SCD) is an autosomal recessive abnormality of the beta-globin chain of hemoglobin (Hb), resulting in poorly deformable sickled cells that cause microvascular occlusion and hemolytic anemia. The spleen is almost always affected by SCD, with microinfarcts within the first 36 months of life resulting in splenic atrophy. Acute liver disorders causing right-sided abdominal pain include acute vaso-occlusive crisis, liver infarction, and acute hepatic crisis. Chronic liver disease might be due to hemosiderosis and hepatitis and possibly to SCD itself if small, clinically silent microvascular occlusions occur chronically. Black pigment gallstones caused by elevated bilirubin excretion are common. Their small size permits them to travel into the common bile duct but cause only low-grade obstruction, so hyperbilirubinemia rather than bile duct dilatation is typical. Whether cholecystectomy should be done in asymptomatic individuals is controversial. The most common laboratory abnormality is an elevation of unconjugated bilirubin level. Bilirubin and lactate dehydrogenase levels correlate with one another, suggesting that chronic hemolysis and ineffective erythropoiesis, rather than liver disease, are the sources of hyperbilirubinemia. Abdominal pain is very common in SCD and is usually due to sickling, which resolves with supportive care. Computed tomography scans might be ordered for severe or unremitting pain. The liver typically shows sickled erythrocytes and Kupffer cell enlargement acutely and hemosiderosis chronically. The safety of liver biopsies has been questioned, particularly during acute sickling crisis. Treatments include blood transfusions, exchange transfusions, iron-chelating agents, hydroxyurea, and allogeneic stem-cell transplantation. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Ultrasonic assessment of the prevalence of gall stones in sickle cell ...

African Journals Online (AJOL)

Background: Gallstone is a common problem in patients with sickle cell disease. Prevalence of this problem among sickle cell disease (SCD) children may vary with age, and geographic location. Studies on gallstone prevalence in SCD children are scanty in the South-South zone of Nigeria. Aim: To determine by ...

Enhanced parenting knowledge and skills in mothers of preschool children with sickle cell disease.

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Schuman, W B; Armstrong, F D; Pegelow, C H; Routh, D K

1993-10-01

Compared 25 preschool children with sickle cell disease (SCD) to demographically matched healthy comparison children on maternal reports of child-rearing beliefs and practices and maternal and child behaviors related to social adjustment. Mothers of children with SCD possessed significantly more knowledge of appropriate discipline techniques. The groups did not differ on maternal reports of socially relevant child behavior. However, when mother-child interactions were observed in free play and structured play settings, mothers of children with SCD treated their children as competent significantly more, and treated their children as incompetent significantly less, than comparison mothers. Mothers of children with SCD also used significantly more reinforcement during the final toy pick-up condition. There were no observed differences between groups in the children's behavior.

Religious coping and the use of prayer in children with sickle cell disease.

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Cotton, Sian; Grossoehme, Daniel; McGrady, Meghan E

2012-02-01

While adolescents and adults with sickle cell disease (SCD) have reported using religion to cope with SCD, there is no data examining religious coping in young children with SCD. The purpose of this qualitative study was to: (1) describe the types of religious coping used by children with SCD; (2) describe the content and frequency of prayer used in relation to SCD; and (3) examine how children viewed God/Higher Power in relation to their SCD. Children with SCD participated in a semi-structured interview and an art drawing exercise focused on the use of general coping and religious coping. Interviews were coded, organized, and analyzed using a template organizational style of interpretation and NVivo 8.0 qualitative software. Of the 19 participants, the average age was 8.05 years (SD ±1.81); 11 were female (58%); all (100%) were African-American and 9 (47%) were Protestant. Children used religion to gain control, make meaning, and find comfort. Most children reported praying to get well, to keep from getting sick, and to get out of the hospital. Children described a functional God who made them take their medicine or took them to the hospital and an emotional God who made them happy and comforted them when they were sad or scared. These children with SCD reported using religion to help cope with the illness. Providers should be aware of the importance of religion to many of these children and integrate religion, as appropriate, into discussions about coping with SCD. Copyright © 2011 Wiley Periodicals, Inc.

Preventing tomorrow's sudden cardiac death today: part I: Current data on risk stratification for sudden cardiac death.

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Al-Khatib, Sana M; Sanders, Gillian D; Bigger, J Thomas; Buxton, Alfred E; Califf, Robert M; Carlson, Mark; Curtis, Anne; Curtis, Jeptha; Fain, Eric; Gersh, Bernard J; Gold, Michael R; Haghighi-Mood, Ali; Hammill, Stephen C; Healey, Jeff; Hlatky, Mark; Hohnloser, Stefan; Kim, Raymond J; Lee, Kerry; Mark, Daniel; Mianulli, Marcus; Mitchell, Brent; Prystowsky, Eric N; Smith, Joseph; Steinhaus, David; Zareba, Wojciech

2007-06-01

Accurate and timely prediction of sudden cardiac death (SCD) is a necessary prerequisite for effective prevention and therapy. Although the largest number of SCD events occurs in patients without overt heart disease, there are currently no tests that are of proven predictive value in this population. Efforts in risk stratification for SCD have focused primarily on predicting SCD in patients with known structural heart disease. Despite the ubiquity of tests that have been purported to predict SCD vulnerability in such patients, there is little consensus on which test, in addition to the left ventricular ejection fraction, should be used to determine which patients will benefit from an implantable cardioverter defibrillator. On July 20 and 21, 2006, a group of experts representing clinical cardiology, cardiac electrophysiology, biostatistics, economics, and health policy were joined by representatives of the US Food and Drug administration, Centers for Medicare Services, Agency for Health Research and Quality, the Heart Rhythm Society, and the device and pharmaceutical industry for a round table meeting to review current data on strategies of risk stratification for SCD, to explore methods to translate these strategies into practice and policy, and to identify areas that need to be addressed by future research studies. The meeting was organized by the Duke Center for the Prevention of SCD at the Duke Clinical Research Institute and was funded by industry participants. This article summarizes the presentations and discussions that occurred at that meeting.

Mothers Raising Children with Sickle Cell Disease at the Intersection of Race, Gender, and Illness Stigma

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Burnes, David P. R.; Antle, Beverley J.; Williams, Charmaine C.; Cook, Lisa

2008-01-01

This qualitative study used the long interview method with Canadian mothers of African and Caribbean descent to understand the underresearched experience of raising a child with sickle cell disease (SCD). Mothers' realities were explored through three levels of social organization: daily caregiver coping (micro level); community views of SCD, such…

[Worldwide experience with automated external defibrillators: What have we achieved? What else can we expect?].

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Trappe, Hans-Joachim

2016-03-01

In Germany approximately 70,000-100,000 SCD patients die from sudden cardiac death (SCD). SCD is not caused by a single factor but is a multifactorial problem. In 50 % of SCD victims, sudden cardiac death is the first manifestation of heart disease. SCD is caused by ventricular tachyarrhythmias in approximately 90 % of patients, whereas SCD is caused by bradyarrhythmias in 5-10 % of the patients. Risk stratification is not possible in the majority of them prior to the fatal event. Early defibrillation is the method of choice to terminate ventricular fibrillation. Therefore, it is mandatory to install automatic external defibrillators (AED) in places with many people. There is general agreement that early defibrillation with automated external defibrillators (AED) is an effective tool to treat patients with ventricular fibrillation and will improve survival. It seems necessary to teach cardiocompression and AED use, also to children and adolescents. AED therapy "at home" did not improve survival in patients with cardiac arrest and can not be recommended.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

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Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

Science.gov (United States)

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening program

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Pierobon Marta

2009-06-01

Full Text Available Abstract Background Stroke is a serious complication of sickle cell disease (SCD in children. Transcranic Doppler (TCD is a well-established predictor of future cerebrovascular symptoms: a blood flow velocity >200 cm/sec in the Middle Cerebral Artery (MCA correlates with a high risk of stroke in cohorts of African-american HbS/HbS patients. In North-East Italy the recent increase in SCD patients is mainly due to immigration from Africa. A comprehensive care program for children with SCD was established in our Center since 2004, but a wide and routine screening for Primary stroke prevention needs to be developed. Methods In order to verify the feasibility of TCD and Transcranial color coded Sonography (TCCS screening in our setting and the applicability of international reference values of blood velocities to our population of African immigrants with HbS/HbS SCD, we performed TCD and TCCD in 12 HbS/HbS African children and two groups of age-matched controls of Caucasian and African origin respectively. TCD and TCCS were performed on the same day of the scheduled routine hematologic visit after parental education. Results All parents accepted to perform the sonography to their children. TCD and TCCD were performed in all patients and an adequate temporal window could be obtained in all of them. Pulsatility index and depth values in both the MCA and the Basilar Artery (BA were similar at TCD and TCCS evaluation in the three groups while time-average maximum velocities (TAMM, peak systolic velocity and diastolic velocity in the MCA and BA were higher in the patients' group on both TCD and TCCS evaluation. African and Caucasian healthy controls had similar lower values. Conclusion Our preliminary data set the base to further evaluate the implementation of a primary stroke prevention program in our setting of HbS/HbS African immigrants and HbS/beta thalassemia Italians. Parental education-preferably in the native language- on stroke risk and

Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease

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Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

2014-01-01

The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients – the deoxygenation-induced cation pathway (Psickle), the Ca2+-activated K+ channel (the Gardos channel) and the K+–Cl− cotransporter (KCC) – it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K+ permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca2+ through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. PMID:25015917

Effects of 5-hydroxymethyl-2-furfural on the volume and membrane permeability of red blood cells from patients with sickle cell disease.

Science.gov (United States)

Hannemann, Anke; Cytlak, Urszula M; Rees, David C; Tewari, Sanjay; Gibson, John S

2014-09-15

The heterocyclic aldehyde 5-hydroxymethyl-2-furfural (5HMF) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. We hypothesized that should 5HMF also inhibit the main cation pathways implicated in the dehydration of RBCs from SCD patients - the deoxygenation-induced cation pathway (Psickle), the Ca(2+)-activated K(+) channel (the Gardos channel) and the K(+)-Cl(-) cotransporter (KCC) - it would have a synergistic effect in protection against sickling, directly through interacting with HbS, and indirectly through maintaining hydration and reducing [HbS]. This study was therefore designed to investigate the effects of 5HMF on RBC volume and K(+) permeability in vitro. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca(2+) through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

cAMP response element binding protein1 is essential for activation of steroyl co-enzyme a desaturase 1 (Scd1 in mouse lung type II epithelial cells.

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Nisha Antony

Full Text Available Cyclic AMP Response Element-Binding Protein 1 (Creb1 is a transcription factor that mediates cyclic adenosine 3', 5'-monophosphate (cAMP signalling in many tissues. Creb1(-/- mice die at birth due to respiratory failure and previous genome-wide microarray analysis of E17.5 Creb1(-/- fetal mouse lung identified important Creb1-regulated gene targets during lung development. The lipogenic enzymes stearoyl-CoA desaturase 1 (Scd1 and fatty acid synthase (Fasn showed highly reduced gene expression in Creb1(-/- lungs. We therefore hypothesized that Creb1 plays a crucial role in the transcriptional regulation of genes involved in pulmonary lipid biosynthetic pathways during lung development. In this study we confirmed that Scd1 and Fasn mRNA levels were down regulated in the E17.5 Creb1(-/- mouse lung while the lipogenic-associated transcription factors SrebpF1, C/ebpα and Pparγ were increased. In vivo studies using germline (Creb1(-/- and lung epithelial-specific (Creb1(EpiΔ/Δ Creb1 knockout mice showed strongly reduced Scd1, but not Fasn gene expression and protein levels in lung epithelial cells. In vitro studies using mouse MLE-15 epithelial cells showed that forskolin-mediated activation of Creb1 increased both Scd1 gene expression and protein synthesis. Additionally, MLE15 cells transfected with a dominant-negative ACreb vector blocked forskolin-mediated stimulation of Scd1 gene expression. Lipid profiling in MLE15 cells showed that dominant-negative ACreb suppressed forskolin-induced desaturation of ether linked lipids to produce plasmalogens, as well as levels of phosphatidylethanolamine, ceramide and lysophosphatidylcholine. Taken together these results demonstrate that Creb1 is essential for the induction and maintenance of Scd1 in developing fetal mouse lung epithelial cells.

Novel loci associated with increased risk of sudden cardiac death in the context of coronary artery disease.

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Adriana Huertas-Vazquez

Full Text Available Recent genome-wide association studies (GWAS have identified novel loci associated with sudden cardiac death (SCD. Despite this progress, identified DNA variants account for a relatively small portion of overall SCD risk, suggesting that additional loci contributing to SCD susceptibility await discovery. The objective of this study was to identify novel DNA variation associated with SCD in the context of coronary artery disease (CAD.Using the MetaboChip custom array we conducted a case-control association analysis of 119,117 SNPs in 948 SCD cases (with underlying CAD from the Oregon Sudden Unexpected Death Study (Oregon-SUDS and 3,050 controls with CAD from the Wellcome Trust Case-Control Consortium (WTCCC. Two newly identified loci were significantly associated with increased risk of SCD after correction for multiple comparisons at: rs6730157 in the RAB3GAP1 gene on chromosome 2 (P = 4.93×10(-12, OR = 1.60 and rs2077316 in the ZNF365 gene on chromosome 10 (P = 3.64×10(-8, OR = 2.41.Our findings suggest that RAB3GAP1 and ZNF365 are relevant candidate genes for SCD and will contribute to the mechanistic understanding of SCD susceptibility.

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

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Shi, Jun; Ge, Meili; Li, Xingxin; Shao, Yingqi; Yao, Jianfeng; Zheng, Yizhou

2014-01-01

Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-γ-producing T cells have been found in AA. CD30, a surface protein belonging to the tumor necrosis factor receptor family and releasing from cell surface as a soluble form (sCD30) after activation, marks a subset of activated T cells secreting IFN-γ when exposed to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in patients with SAA, which were closely correlated with disease severity, including absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted that sCD30 levels were positively correlated with plasma IFN-γ levels and CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena, we stimulated T cells with alloantigen in vitro and found that CD30+ T cells were the major source of IFN-γ, and induced CD30+ T cells from patients with SAA produced significantly more IFN-γ than that from healthy individuals. In addition, increased proportion of CD8+ T cells in AA showed enhanced allogeneic response by the fact that they expressed more CD30 during allogeneic stimulation. sCD30 levels decreased in patients responded to immunosuppressive therapy. In conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30+ T cell-mediated immune response in SAA. CD30 as a molecular marker that transiently expresses on IFN-γ-producing T cells, may participate in mediating bone marrow failure in AA, which also can facilitate our understanding of AA pathogenesis to identify new therapeutic targets. PMID:25383872

Sickle Cell Disease and Pulmonary Hypertension

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... My doctor wants to screen me for pulmonary hypertension. Why is this? Sickle cell disease (SCD), a ... What are some of the symptoms of pulmonary hypertension? Because they are somewhat general symptoms, the characteristics ...

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

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Carrillo, E H; Gordon, L; Goode, E; Davis, E; Polk, H C

2001-05-01

Elevated levels of soluble CD14 (sCD14) have been implicated in both gram-positive and gram-negative sepsis, and it has been associated with high mortality in trauma patients who become infected. Eleven healthy volunteers and 25 adult trauma patients with multiple injuries and a mean Injury Severity Score of 32 participated. Whole blood was obtained at intervals. Immunohistochemistry was used to quantify membrane CD14 (mCD14), by flow cytometry and plasma levels of sCD14 by enzyme-linked immunosorbent assay. Analysis of variance and Student's T test with Mann-Whitney posttest were used to determine significance at p < 0.05. On posttrauma day 1, sCD14 was significantly different in the plasma of infected patients compared with normal controls (7.16 +/- 1.87 microg/mL vs. 4.4 +/- 0.92 microg/mL, p < 0.01), but not significantly different from noninfected patients. The percentage of monocytes expressing mCD14 in trauma patients did not differentiate them from normal controls; however, mCD14 receptor density did demonstrate significance in septic trauma patients (n = 15) versus normal controls on posttrauma day 3 (p = 0.0065). On the basis of our data, mCD14 did not differentiate infected and noninfected trauma patients, although trauma in general reduced mCD14 and elevated sCD14. Interestingly, 100% of patients who exceeded plasma levels of 8 microg/mL of sCD14 on day 1 after injury developed infections. Therefore, early high expressers of sCD14 may be at higher risk for infectious complications after trauma.

Socio-environmental exposures and health outcomes among persons with sickle cell disease

OpenAIRE

Asnani, Monika R.; Knight Madden, Jennifer; Reid, Marvin; Greene, Lisa-Gaye; Lyew-Ayee, Parris

2017-01-01

There is much variability in the expression of sickle cell disease (SCD) and recent works suggest that environmental and social factors may also influence this variability. This paper aims to use geographic information systems technology to examine the association between socio-environmental exposures and health outcomes in all persons who have attended or currently attend the Sickle Cell Unit in Jamaica. Rural patients presented for clinical care at older ages and had less annual visits to c...

The Role of Blood Transfusion in the Management of Sickle Cell ...

African Journals Online (AJOL)

, in patients with sickle cell disease (SCD). There is general lack of appreciation by clinicians, of the sub-optimal or frankly harmful effects, of inappropriate transfusion in SCD. This article discusses the relevant pathophysiology of sickle cell ...

Sickle Cell Disease (SCD)

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... talk about donating their baby's cord blood College football player stays true to his commitment Be the ... appointment, the transplant doctor will: Review your medical history Talk with you about your options Discuss the ...

Genetic determinants and stroke in children with sickle cell disease.

Science.gov (United States)

Rodrigues, Daniela O W; Ribeiro, Luiz C; Sudário, Lysla C; Teixeira, Maria T B; Martins, Marina L; Pittella, Anuska M O L; Junior, Irtis de O Fernandes

To verify genetic determinants associated with stroke in children with sickle cell disease (SCD). Prospective cohort with 110 children submitted to neonatal screening by the Neonatal Screening Program, between 1998 and 2007, with SCD diagnosis, followed at a regional reference public service for hemoglobinopathies. The analyzed variables were type of hemoglobinopathy, gender, coexistence with alpha thalassemia (α-thal), haplotypes of the beta globin chain cluster, and stroke. The final analysis was conducted with 66 children with sickle cell anemia (SCA), using the chi-squared test in the program SPSS ® version 14.0. Among children with SCD, 60% had SCA. The prevalence of coexistence with α-thal was 30.3% and the Bantu haplotype (CAR) was identified in 89.2%. The incidence of stroke was significantly higher in those with SCA (27.3% vs. 2.3%; p=0.001) and males (24.1% vs. 9.6%; p=0.044). The presence of α-thal (p=0.196), the CAR haplotype (p=0.543), and socioeconomic factors were not statistically significant in association with the occurrence of stroke. There is a high incidence of stroke in male children and in children with SCA. Coexistence with α-thal and haplotypes of the beta globin chain cluster did not show any significant association with stroke. The heterogeneity between previously evaluated populations, the non-reproducibility between studies, and the need to identify factors associated with stroke in patients with SCA indicate the necessity of conducting further research to demonstrate the relevance of genetic factors in stroke related to SCD. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

A Case of Subacute Combined Degeneration of the Spinal Cord with Infective Endocarditis

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Xiao-Jiang Huang

2015-01-01

Full Text Available Background. Subacute combined degeneration (SCD is a rare cause of demyelination of the dorsal and lateral columns of spinal cord and is a neurogenic complication due to cobalamin deficiency. Anemia of chronic disease (ACD occurs in patients with acute or chronic immune activation, including infective endocarditis. It remains to be elucidated whether ACD patients are more sensitive to suffer from SCD. Little cases about SCD patients accompanied with ACD have been reported till now. Here we reported a 36-year-old man with SCD with a medical history of mitral inadequacy over 20 years, who was admitted and transported from another hospital to our hospital due to an 8-month history of gait disturbance, lower limb weakness and paresthesia, and loss of proprioception. Significant laboratory results and echocardiography suggest iron deficiency anemia and infective endocarditis (IE. The SCD diagnosis was confirmed by MRI, which showed selective demyelination in the dorsal and lateral columns of spinal cord. In conclusion, the ACD patients may suffer from SCD, which can be diagnosed by 3 Tesla magnetic resonance imaging.

Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease

OpenAIRE

Calvet, David; Tuilier, Titien; Mélé, Nicolas; Turc, Guillaume; Habibi, Anoosha; Abdallah, Nassim Ait; Majhadi, Loubna; Hemery, François; Edjlali, Myriam; Galacteros, Frédéric; Bartolucci, Pablo

2017-01-01

Low %HbF is independently associated with silent WMCs on brain imaging in adults with SCD.Our results highlight the potential use of therapeutic strategies inducing HbF expression in SCD patients with silent white matter changes.

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

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Solgi, G; Amirzagar, A A; Pourmand, G; Mehrsai, A R; Taherimahmoudi, M; Baradaran, N; Nicknam, M H; Ebrahimi Rad, M R; Saraji, A; Asadpoor, A A; Moheiydin, M; Nikbin, B

2009-09-01

We investigated the relevance of donor bone marrow cell infusion (DBMI) and serum levels of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and soluble CD30 (sCD30) in kidney recipients. We analyzed the allograft outcomes correlated with sCD30, IFN-gamma, and IL-10 levels using pre- and posttransplantation sera from 40 live donor renal transplants (20 patients with DBMI [2.1 x 10(9) +/- 1.3 x 10(9) mononuclear cells/body] and 20 controls). Patients with acute rejection episodes (ARE)-3/20 DBMI and 6/20 controls-showed increased sCD30 and IFN-gamma as well as decreased IL-10 posttransplantation compared with nonrejectors. Significant differences were observed for sCD30 and IFN-gamma levels: 59.54 vs 30.92 ng/mL (P = .02) and 11.91 vs 3.01 pg/mL (P = .01), respectively. Comparison of pre- and posttransplant levels of IFN-gamma, IL-10, and sCD30 in ARE patients showed higher levels in posttransplant sera except for IFN-gamma in controls (6.37 vs 11.93; P = .01). Increased IFN-gamma and IL-10 were correlated with rejection (r = .93; P = .008). sCD30 correlated with serum creatinine among ARE patients in control and DBMI groups (r = .89; P = .019; and r = 1.00; P sCD30, IFN-gamma, and IL-10 posttransplantation in rejecting patients provided evidence for coexistence of cellular and humoral responses in ARE. There appeared to be a down-regulatory effect of infusion on alloresponses.

Identification of the hot-spot areas for sickle cell disease using cord blood screening at a district hospital: an Indian perspective.

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Dixit, Sujata; Sahu, Pushpansu; Kar, Shantanu Kumar; Negi, Sapna

2015-10-01

Sickle cell disease (SCD), a genetic disorder often reported late, can be identified early in life, and hot-spot areas may be identified to conduct genetic epidemiology studies. This study was undertaken to estimate prevalence and to identify hot spot area for SCD in Kalahandi district, by screening cord blood of neonates delivered at the district hospital as first-hand information. Kalahandi District Hospital selected for the study is predominated by tribal population with higher prevalence of SCD as compared to other parts of Odisha. Cord blood screening of SCD was carried out on 761 newborn samples of which 13 were screened to be homozygous for SCD. Information on area of parent's residence was also collected. Madanpur Rampur area was found to be with the highest prevalence of SCD (10.52 %) and the gene distribution did not follow Hardy-Weinberg Equation indicating un-natural selection. The approach of conducting neonatal screening in a district hospital for identification of SCD is feasible and appropriate for prioritizing area for the implementation of large-scale screening and planning control measures thereof.

Thinner cortex in patients with subjective cognitive decline is associated with steeper decline of memory.

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Verfaillie, Sander C J; Slot, Rosalinde E; Tijms, Betty M; Bouwman, Femke; Benedictus, Marije R; Overbeek, Jozefien M; Koene, Teddy; Vrenken, Hugo; Scheltens, Philip; Barkhof, Frederik; van der Flier, Wiesje M

2018-01-01

We aimed to investigate associations between regional cortical thickness and rate of decline over time in 4 cognitive domains in patients with subjective cognitive decline (SCD). We included 233 SCD patients with the total number of 654 neuropsychological assessments (median = 3, range = 2-8) and available baseline magnetic resonance imaging from the Amsterdam Dementia Cohort (125 males, age: 63 ± 9, Mini-Mental State Examination score: 28 ± 2). We assessed longitudinal cognitive functioning at baseline and follow-up in 4 cognitive domains (composite Z-scores): memory, attention, executive function, and language. Thickness (millimeter) was estimated using FreeSurfer for frontal, temporal, parietal, cingulate, and occipital cortices. We used linear mixed models to estimate effects of cortical thickness on cognitive performance (dependent variables). There were no associations between cortical thickness and baseline cognition, but a faster subsequent rate of memory loss was associated with thinner cortex of the frontal [β (SE) = 0.20 (0.07)], temporal [β (SE) = 0.18 (0.07)], and occipital [β (SE) = 0.22 (0.09)] cortices (all p cognitive decline related to neurodegenerative diseases, most prominently Alzheimer's disease. Copyright © 2017 Elsevier Inc. All rights reserved.

MITRAL VALVE PROLAPSE AND SUDDEN CARDIAC DEATH: WHO IS IN THE RISK GROUP?

Directory of Open Access Journals (Sweden)

O. E. Shirobokikh

2016-01-01

Full Text Available Mitral valve prolapse (MVP is a congenital heart disease, fairly widespread in the population (2-8%. It rarely has complications, but they are serious and include sudden cardiac death (SCD, risk of which rises twofold from 0.2-0.4% cases by MVP. Most deaths are observed among young healthy women. This work is a review of literature dedicated to connection between MVP and SCD designed to explore possible predicts of SCD within patients suffering from MVP and to determine the subset of patients. A conclusion has been made that the connection between MVP and SCD is realized through life-threatening ventricular arrhythmias (VT, VF. The most common site of arrhythmias origin is the inferobasal left ventricular wall. A high-risk subset of patients is determined as young adult women with a midsystolic click at auscultation, bileaflet involvement of the mitral valve, T-wave abnormalities on inferior leads (II, III, aVF and frequent complex ventricular ectopic activity. Such patients require more intensive disease management of ventricular arrhythmias including consideration of surgical treatment.

Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

DEFF Research Database (Denmark)

Kragstrup, Tue Wenzel; Jalilian, Babak; Keller, Kresten Krarup

2016-01-01

in murine models of rheumatoid arthritis. Methods The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice...... associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above...

Magnetic resonance imaging in children with sickle cell disease - detecting alterations in the apparent diffusion coefficient in hips with avascular necrosis

International Nuclear Information System (INIS)

MacKenzie, John D.; Hernandez, Andrea; Pena, Andres; Khrichenko, Dmitry; Gonzalez, Leonardo; Jaramillo, Diego; Ruppert, Kai; Jawad, Abbas F.; Wells, Lawrence; Smith-Whitley, Kim

2012-01-01

Avascular necrosis (AVN) is a common morbidity in children with sickle cell disease (SCD) that leads to pain and joint immobility. However, the diagnosis is often uncertain or delayed. To examine the ability of apparent diffusion coefficient (ADC) measurements on diffusion-weighted imaging to detect AVN in children with SCD. ADC values were calculated at the hips of normal children (n = 19) and children with SCD who were either asymptomatic with no known previous hip disease (n = 13) or presented for the first time with clinical symptoms of hip pathology (n = 12). ADC values were compared for differences among groups with and without AVN using non-parametric statistical methods. The ADC values were elevated in the hips of children with AVN (median ADC = 1.57 x 10 -3 mm 2 /s [95% confidence interval = 0.86-2.10]) and differed significantly in pairwise comparisons (all P < 0.05) from normal children (0.74 [0.46-0.98]), asymptomatic children with SCD (0.55 [0.25-0.85]), and SCD children who had symptoms referable to their hips but did not show findings of hip AVN on conventional MRI or radiographs (0.46 [0.18-0.72]). Children with sickle cell disease have elevated apparent diffusion coefficient values in their affected hips on initial diagnosis of avascular necrosis. (orig.)

Magnetic resonance imaging in children with sickle cell disease - detecting alterations in the apparent diffusion coefficient in hips with avascular necrosis

Energy Technology Data Exchange (ETDEWEB)

MacKenzie, John D. [Children' s Hospital of Philadelphia, Department of Pediatric Radiology, Philadelphia, PA (United States); UCSF Benioff Children' s Hospital, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Hernandez, Andrea; Pena, Andres; Khrichenko, Dmitry; Gonzalez, Leonardo; Jaramillo, Diego [Children' s Hospital of Philadelphia, Department of Pediatric Radiology, Philadelphia, PA (United States); Ruppert, Kai [Children' s Hospital of Philadelphia, Department of Pediatric Radiology, Philadelphia, PA (United States); University of Virginia, Department of Radiology, Charlottesville, VA (United States); Jawad, Abbas F. [Children' s Hospital of Philadelphia, Department of Pediatrics, Philadelphia, PA (United States); Wells, Lawrence [Children' s Hospital of Philadelphia, Department of Orthopedics, Philadelphia, PA (United States); Smith-Whitley, Kim [Children' s Hospital of Philadelphia, Department of Hematology, Philadelphia, PA (United States)

2012-06-15

Avascular necrosis (AVN) is a common morbidity in children with sickle cell disease (SCD) that leads to pain and joint immobility. However, the diagnosis is often uncertain or delayed. To examine the ability of apparent diffusion coefficient (ADC) measurements on diffusion-weighted imaging to detect AVN in children with SCD. ADC values were calculated at the hips of normal children (n = 19) and children with SCD who were either asymptomatic with no known previous hip disease (n = 13) or presented for the first time with clinical symptoms of hip pathology (n = 12). ADC values were compared for differences among groups with and without AVN using non-parametric statistical methods. The ADC values were elevated in the hips of children with AVN (median ADC = 1.57 x 10{sup -3} mm{sup 2}/s [95% confidence interval = 0.86-2.10]) and differed significantly in pairwise comparisons (all P < 0.05) from normal children (0.74 [0.46-0.98]), asymptomatic children with SCD (0.55 [0.25-0.85]), and SCD children who had symptoms referable to their hips but did not show findings of hip AVN on conventional MRI or radiographs (0.46 [0.18-0.72]). Children with sickle cell disease have elevated apparent diffusion coefficient values in their affected hips on initial diagnosis of avascular necrosis. (orig.)

Pulmonary hypertension in sickle cell disease children under 10 years of age.

Science.gov (United States)

Colombatti, Raffaella; Maschietto, Nicola; Varotto, Elena; Grison, Alessandra; Grazzina, Nicoletta; Meneghello, Linda; Teso, Simone; Carli, Modesto; Milanesi, Ornella; Sainati, Laura

2010-09-01

Despite the finding of elevated Tricuspid Regurgitant Velocity (TRV) in children below 5 years of age, the prevalence and evolution of Pulmonary Hypertension (PH) in young children with sickle cell disease (SCD) are unclear. In order to identify predictive factors of precocious PH development, SCD children > or =3 years old, at steady state, underwent annual echocardiography and Tissue Doppler Imaging (TDI). Patients receiving chronic transfusion were excluded. Thirty-seven of seventy-five patients were > or =3 years, with measurable TRV. In our young population (mean age 6.2 years) of mainly African, HbS/HbS patients, 8/37 (21.6%) had TRV > or =2.5 m/s, 8% being only 3 years old. Significant correlation was found between precocious TRV elevation and high platelet and reticulocyte counts and frequent acute chest syndromes (ACS). In multivariate analysis, ACS was the only variable predicting TRV > or =2.5 m/s. TDI of the 37 patients showed signs of diastolic dysfunction of the left ventricle. At follow-up all eight patients with high TRV displayed further increase and seven more developed TRV > or =2.5 m/s. PH seems to begin in children earlier than expected. Factors involved in its early onset might be different from the ones causing its development in older children or adults. African children might benefit from early screening and re-assessment once a year.

Impact of individualized pain plan on the emergency management of children with sickle cell disease.

Science.gov (United States)