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

PubMed

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.

Changes in SCD gene DNA methylation after bariatric surgery in morbidly obese patients are associated with free fatty acids

PubMed Central

Morcillo, Sonsoles; Martín-Núñez, Gracia Mª; García-Serrano, Sara; Gutierrez-Repiso, Carolina; Rodriguez-Pacheco, Francisca; Valdes, Sergio; Gonzalo, Montserrat; Rojo-Martinez, Gemma; Moreno-Ruiz, Francisco J.; Rodriguez-Cañete, Alberto; Tinahones, Francisco; García-Fuentes, Eduardo

2017-01-01

Stearoyl CoA Desaturase-1 (SCD) is considered as playing an important role in the explanation of obesity. The aim of this study was to evaluate whether the DNA methylation SCD gene promoter is associated with the metabolic improvement in morbidly obese patients after bariatric surgery. The study included 120 subjects with morbid obesity who underwent a laparoscopic Roux-en Y gastric by-pass (RYGB) and a control group of 30 obese subjects with a similar body mass index (BMI) to that found in morbidly obese subjects six months after RYGB. Fasting blood samples were obtained before and at six months after RYGB. DNA methylation was measured by pyrosequencing technology. DNA methylation levels of the SCD gene promoter were lower in morbidly obese subjects before bariatric surgery but increased after RYGB to levels similar to those found in the control group. Changes of DNA methylation SCD gene were associated with the changes of free fatty acids levels (r = −0.442, p = 0.006) and HOMA-IR (r = −0.249, p = 0.035) after surgery. RYGB produces an increase in the low SCD methylation promoter levels found in morbidly obese subjects. This change of SCD methylation levels is associated with changes in FFA and HOMA-IR. PMID:28393901

Decreased serum levels of sCD40L and IL-31 correlate in treated patients with Relapsing-Remitting Multiple Sclerosis.

PubMed

de J Guerrero-García, José; Rojas-Mayorquín, Argelia E; Valle, Yeminia; Padilla-Gutiérrez, Jorge R; Castañeda-Moreno, Víctor A; Mireles-Ramírez, Mario A; Muñoz-Valle, José F; Ortuño-Sahagún, Daniel

2018-01-01

The CD40/CD40L system is a binding key for co-stimulation of immune cells. Soluble form of CD40L has been widely studied as marker of inflammatory and autoimmune diseases. Here we analyze serum concentrations of sCD40L, as well as 14 cytokines, in patients with Multiple Sclerosis (MS) treated with Glatiramer acetate or Interferon beta. In the healthy control group, we found in serum a highly positive correlation between sCD40L and Interleukin (IL)-31, an anti-inflammatory Th2 cytokine. Additionally, an important reduction in IL-31 and sCD40L serum levels, as well as a significant reduction in CD40 mRNA expression and complete depletion of CD40L mRNA, detected from peripheral blood cells, was found in treated patients with MS. Therefore, sCD40L and IL-31 must be taken into account as possible prognostic markers when analyzing the disease progress of MS in order to provide more personalized treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

Reduced sTWEAK and Increased sCD163 Levels in HIV-Infected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

PubMed Central

Beltrán, Luis M.; García Morillo, José S.; Egido, Jesús; Noval, Manuel Leal; Ferrando-Martinez, Sara; Blanco-Colio, Luis M.; Genebat, Miguel; Villar, José R.; Moreno-Luna, Rafael; Moreno, Juan Antonio

2014-01-01

Background Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immune-activation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART. PMID:24594990

Orbital and attitude evolution of SCD-1 and SCD-2 Brazilian satellites

NASA Astrophysics Data System (ADS)

Murcia, J. O.; Carrara, V.; Kuga, H. K.

2017-10-01

The SCD-1 and SCD-2 satellites were launched in 1993 and 1998, respectively, with use of the Launcher “Pegasus” of the OSC (Orbital Sciences Corporation). 21 and 16 years later, the satellites are still in orbit around the Earth and providing data for users. Mission and Operational data from Satellite Tracking Center Network are stored in mission files in the Satellite Control Center (SCC) and made available to the users. The SCC also stores history files of the satellite orbit and attitude ephemeris, besides the on-board telemetry, temperatures, equipment status, etc. This work will present some analysis of the orbit ephemeris evolution based upon the Two-Line Elements sets (TLE’s) obtained from NORAD (North American Aerospace Defense Command). Attitude evolution along time is also presented for both satellites from SCC data. The orbit decay will be explained as resulting mainly due to the solar activity during the satellite lifetime. This work aims to report the history of more than 20 years of continuous operation of SCD-1 and SCD-2. At the end, an estimation of the orbital decay is forecast with the use of NASA’s DAS software.

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

PubMed

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

Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (sCD163) in Sepsis, a Prospective Study

PubMed Central

Feng, Lin; Zhou, Xin; Su, Long-Xiang; Feng, Dan; Jia, Yan-Hong; Xie, Li-Xin

2012-01-01

Objective We investigated serum soluble CD163 (sCD163) levels for use in the diagnosis, severity assessment, and prognosis of sepsis in the critical ill patients and compared sCD163 with other infection-related variables. Methods During july 2010 and April 2011, serum was obtained from 102 sepsis patients (days 1, 3, 5, 7, and 10 after admission to an ICU) and 30 systemic inflammatory response syndrome (SIRS) patients with no sepsis diagnosed. Serum levels of sCD163, procalcitonon (PCT), and C reactive protein (CRP) were determined respectively. Sequential organ failure assessment (SOFA) scores for sepsis patients were also recorded. Then evaluated their roles in sepsis. Results The sCD163 levels were 0.88(0.78–1.00)ug/mL for SIRS patients, 1.50(0.92–2.00)ug/mL for moderate sepsis patients, and 2.95(2.18–5.57)ug/mL for severe sepsis patients on day1. The areas under the ROC curves for sCD163, CRP, and PCT for the diagnosis of sepsis were, respectively, 0.856(95%CI: 0.791–0.921), 0.696(95%CI: 0.595–0.797), and 0.629(95%CI: 0.495–0.763), At the recommended cut-off 1.49 ug/mL for sCD163, the sensitivity is 74.0% with 93.3% specificity. Based on 28-day survivals, sCD163 levels in the surviving group stay constant, while they tended to gradually increase in the non-surviving group.The area under the ROC curve for sCD163 for sepsis prognosis was 0.706(95%CI 0.558–0.804). Levels of sCD163 with cut-off point >2.84 ug/mL have sensitivity of 55.8.0%, specificity 80.4%.Common risk factors for death and sCD163 were included in multivariate logistic regression analysis; the odds ratios (OR) for sCD163 and SOFA scores for sepsis prognosis were 1.173 and 1.396, respectively (P<0.05). Spearman rank correlation analysis showed that sCD163 was weakly, but positively correlated with CRP, PCT, and SOFA scores (0.2< r <0.4, P<0.0001), but not with leukocyte counts (r <0.2, P = 0.450). Conclusion Serum sCD163 is superior to PCT and CRP for the diagnosis of sepsis and

SCD-HeFT: Use of RR Interval Statistics for Long-term Risk Stratification for Arrhythmic Sudden Cardiac Death

PubMed Central

Au-yeung, Wan-tai M.; Reinhall, Per; Poole, Jeanne E.; Anderson, Jill; Johnson, George; Fletcher, Ross D.; Moore, Hans J.; Mark, Daniel B.; Lee, Kerry L.; Bardy, Gust H.

2015-01-01

Background In the SCD-HeFT a significant fraction of the congestive heart failure (CHF) patients ultimately did not die suddenly from arrhythmic causes. CHF patients will benefit from better tools to identify if ICD therapy is needed. Objective To identify predictor variables from baseline SCD-HeFT patients’ RR intervals that correlate to arrhythmic sudden cardiac death (SCD) and mortality and to design an ICD therapy screening test. Methods Ten predictor variables were extracted from pre-randomization Holter data from 475 patients enrolled in the SCD-HeFT ICD arm using novel and traditional heart rate variability methods. All variables were correlated to SCD using Mann Whitney-Wilcoxon test and receiver operating characteristic analysis. ICD therapy screening tests were designed by minimizing the cost of false classifications. Survival analysis, including log-rank test and Cox models, was also performed. Results α1 and α2 from detrended fluctuation analysis, the ratio of low to high frequency power, the number of PVCs per hour and heart rate turbulence slope are all statistically significant for predicting the occurrences of SCD (p<0.001) and survival (log-rank p<0.01). The most powerful multivariate predictor tool using the Cox Proportional Hazards was α2 with a hazard ratio of 0.0465 (95% CI: 0.00528 – 0.409, p<0.01). Conclusion Predictor variables from RR intervals correlate to the occurrences of SCD and distinguish survival among SCD-HeFT ICD patients. We believe SCD prediction models should incorporate Holter based RR interval analysis to refine ICD patient selection especially in removing patients who are unlikely to benefit from ICD therapy. PMID:26096609

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

PubMed

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 < 0.05). There is a significantly relation at the 7th day after kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P < 0.01). There is no obviously relation at 28th day after 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.

Pharmacokinetics and Analgesic Effects of Methadone in Children and Adults with Sickle Cell Disease

PubMed Central

Horst, Jennifer; Frei-Jones, Melissa; Deych, Elena; Shannon, William; Kharasch, Evan D.

2017-01-01

Background Vaso-occlusive episodes (VOE) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in children and adults with SCD, with a secondary aim to assess pain relief and opioid consumption. Procedure Participants included children (<18 yr) and adults with a VOE requiring hospitalization. Patients were randomly assigned to receive standard care (opioid patient controlled analgesia; control group) or one dose of intravenous methadone (0.1–0.125 mg/kg) in addition to standard care (methadone group). Venous methadone and metabolite concentrations were measured. Pain scores, pain relief scores, and opioid consumption were recorded. Results Twenty-four children (12 methadone, 12 controls) and twenty-three adults (11 methadone, 12 controls) were studied. In children, the half-life of R-and S-methadone enantiomers was 34±16 and 24±9 hr, respectively. In adults, R- and S-methadone half-lives were 52±17 and 38±12 hr. Pain scores were lower (p=0.002) and pain relief scores were higher (p=0.0396) in children receiving methadone vs controls. There was no difference in pain scores and pain relief in adults receiving methadone vs controls. There was no difference in opioid consumption between methadone and control groups, in both adults and children. Conclusions Intravenous methadone disposition in children and adults with SCD was comparable to subjects without SCD from prior studies. Methadone produced more pain relief than standard care in children with SCD. Higher methadone doses may be more effective and should be evaluated in both children and adults with SCD. PMID:27572136

Parental substance abuse, reports of chronic pain and coping in adult patients with sickle cell disease.

PubMed Central

Edwards, Christopher; Whitfield, Keith; Sudhakar, Shiv; Pearce, Michele; Byrd, Goldie; Wood, Mary; Feliu, Miriam; Leach-Beale, Brittani; DeCastro, Laura; Whitworth, Elaine; Abrams, Mary; Jonassaint, Jude; Harrison, M. Ojinga; Mathis, Markece; Scott, Lydia; Johnson, Stephanie; Durant, Lauren; Holmes, Anita; Presnell, Katherine; Bennett, Gary; Shelby, Rebecca; Robinson, Elwood

2006-01-01

There is increasing interest from a social learning perspective in understanding the role of parental factors on adult health behaviors and health outcomes. Our review revealed no studies, to date, that have evaluated the effects of parental substance abuse on reports of chronic pain and coping in adult patients with sickle cell disease (SCD). We explored the effects of parental substance (alcohol or drug) abuse on reports of the sensory, affective and summary indices of pain in 67 adult patients, mean age 38.9 (13.5), with SCD. We also explored the effects of parental substance abuse on psychopathology associated with pain and active coping. Twenty-four percent of patients reported that their parent(s) abused substances. Patients whose parent(s) were characterized as substance abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS; p=0.02) indices of pain as compared to their counterparts, whose parent(s) were not characterized as substance abusers. Patients did not differ in average age, education or the propensity to respond in a socially acceptable manner. There was a significant trend towards patients who characterized their parents as abusers scoring higher than their counterparts on active coping. We propose a Social Learning Theory to explain the current findings and suggest a need for additional prospective research to simultaneously explore biological (genetic) and social factors that influence the interpretation, experience and reporting of chronic pain in adult patients with chronic disease. PMID:16573309

Reduced sCD36 following weight loss corresponds to improved insulin sensitivity, dyslipidemia and liver fat in obese children.

PubMed

Knøsgaard, L; Kazankov, K; Birkebæk, N H; Holland-Fischer, P; Lange, A; Solvig, J; Hørlyck, A; Kristensen, K; Rittig, S; Vilstrup, H; Grønbæk, H; Handberg, A

2016-09-01

Childhood obesity is a major health problem with serious long-term metabolic consequences. CD36 is important for the development of obesity-related complications among adults. We aimed to investigate circulating sCD36 during weight loss in childhood obesity and its associations with insulin resistance, dyslipidemia, hepatic fat accumulation and low-grade inflammation. The impact of a 10-week weight loss camp for obese children (N=113) on plasma sCD36 and further after a 12-month follow-up (N=68) was investigated. Clinical and biochemical data were collected, and sCD36 was measured by an in-house assay. Liver fat was estimated by ultrasonography and insulin resistance by the homeostasis model assessment (HOMA-IR). Along with marked weight loss, sCD36 was reduced by 21% (P=0.0013) following lifestyle intervention, and individual sCD36 reductions were significantly associated with the corresponding decreases in HOMA-IR, triglycerides and total cholesterol. The largest sCD36 decrease occurred among children who reduced HOMA-IR and liver fat. After 12 months of follow-up, sCD36 was increased (P=0.014) and the metabolic improvements were largely lost. Weight-loss-induced sCD36 reduction, coincident with improved insulin resistance, circulating lipids and hepatic fat accumulation, proposes that sCD36 may be an early marker of long-term health risk associated with obesity-related complications.

Posttransplant sCD30 as a biomarker to predict kidney graft outcome.

PubMed

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.

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

PubMed Central

2013-01-01

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. PMID:23414938

Post-transplant sCD30 and neopterin as predictors of chronic allograft nephropathy: impact of different immunosuppressive regimens.

PubMed

Weimer, R; Süsal, C; Yildiz, S; Staak, A; Pelzl, S; Renner, F; Dietrich, H; Daniel, V; Kamali-Ernst, S; Ernst, W; Padberg, W; Opelz, G

2006-08-01

Immunological monitoring for chronic allograft nephropathy (CAN) is of great potential interest. We assessed serum soluble CD30 (sCD30) together with in vitro Th2-type responses (IL-4, IL-10, CD4 helper activity) and neopterin in a prospective study of 84 renal transplant recipients with 2-year follow-up. Patients were randomized to CsA/Aza, CsA/MMF and Tacr/Aza, respectively, to analyze the effect of immunosuppression on posttransplant sCD30 and neopterin. ATG induction and acute rejections did not alter sCD30 levels whereas CMV disease was associated with transient upregulation of sCD30 (p = 0.003 at 4 months) and sustained upregulation of neopterin (corrected for graft function (Neo/CR) p = 0.005 at 2 years). Tacr versus CsA treatment proved to be an independent variable associated with downregulation of 1-year sCD30, which was positively related to Neo/CR (p = 0.007 and 0.01, respectively; logistic regression). Importantly, increased 1-year sCD30 and Neo/CR were associated with decreased glomerular filtration rate at 2 years (p = 0.02 and p < 0.0005, respectively) and evidence of CAN (p < 0.0005). High 1-year sCD30 could not be attributed to enhanced Th2-type responses and was not associated with HLA antibody formation. Our data suggest that elevated sCD30 and neopterin predict graft deterioration by CAN. Tacr effectively downregulates these responses and might be of advantage in patients with elevated sCD30 or neopterin.

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

PubMed

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.

Daily home opioid use in adults with sickle cell disease: The PiSCES project.

PubMed

Smith, Wally R; McClish, Donna K; Dahman, Bassam A; Levenson, James L; Aisiku, Imoigele P; de A Citero, Vanessa; Bovbjerg, Viktor E; Roberts, John D; Penberthy, Lynne T; Roseff, Susan D

2015-01-01

Although opioid prescribing in sickle cell disease (SCD) can be controversial, little is published about patterns of opioid use. To report on home opioid use among adults with SCD. Cohort study. Adults with SCD (n=219) who completed daily pain diaries for up to 6 months and had at least one home pain day. Use of long-acting or short-acting opioids, other analgesics, or adjuvants; the proportion of home days, home pain days, and home crisis days with opioid use; these two outcomes according to patient characteristics. Patients used opioids on 12,311 (78 percent) of 15,778 home pain days. Eighty-five patients (38.8 percent) used long-acting opioids with or without short-acting opioids and 103 (47.0 percent) used only short-acting opioids. Twenty-one (9.6 percent) patients used only non-opioid analgesics and 10 (4.6 percent) used no analgesics. Both pain intensity and pain frequency were higher among opioid users (analysis of variance [ANOVA], p<0.0001). Opioid users used hydroxyurea more often than nonusers, even when controlling for mean pain on pain days. Among all patients, significant relationships were found between any opioid use and somatic symptom burden, SCD stress, negative coping, and physical and mental quality of life (QOL); the relationship with SCD stress and physical QOL remained when controlled for mean pain. Among opioid users, similar associations were found between frequency of opioid use and some disease-related and psychosocial variables. In this adult SCD sample, opioids were used by the majority of patients. Pain was the overwhelming characteristic associated with use, but disease-related and psychosocial variables were also associated.

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

PubMed

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 (P<.0001), 3 (P=.043), and 6 after transplantation (P=.006). Patients with baseline sCD30 levels ≥13.5 ng/mL had lower 12-month bacterial infection-free survival (35.0% vs 80.0%; P<.0001). After adjusting for potential confounders, baseline sCD30 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; <.001). Analogously, 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.

Outcomes of Acute Chest Syndrome in Adult Patients with Sickle Cell Disease: Predictors of Mortality

PubMed Central

Allareddy, Veerajalandhar; Roy, Aparna; Lee, Min Kyeong; Nalliah, Romesh P.; Rampa, Sankeerth; Allareddy, Veerasathpurush; Rotta, Alexandre T.

2014-01-01

Adults with sickle cell disease(SCD) are a growing population. Recent national estimates of outcomes in acute chest syndrome(ACS) among adults with SCD are lacking. We describe the incidence, outcomes and predictors of mortality in ACS in adults. We hypothesize that any need for mechanical ventilation is an independent predictor of mortality. Methods We performed a retrospective analysis of the Nationwide Inpatient Sample(2004–2010),the largest all payer inpatient database in United States, to estimate the incidence and outcomes of ACS needing mechanical ventilation(MV) and exchange transfusion(ET) in patients >21 years. The effects of MV and ET on outcomes including length of stay(LOS) and in-hospital mortality(IHM) were examined using multivariable linear and logistic regression models respectively. The effects of age, sex, race, type of sickle cell crisis, race, co-morbid burden, insurance status, type of admission, and hospital characteristics were adjusted in the regression models. Results Of the 24,699 hospitalizations, 4.6% needed MV(2.7% for <96 hours, 1.9% for ≥96 hours), 6% had ET, with a mean length of stay(LOS) of 7.8 days and an in-hospital mortality rate(IHM) of 1.6%. There was a gradual yearly increase in ACS hospitalizations that needed MV(2.6% in 2004 to 5.8% in 2010). Hb-SS disease was the phenotype in 84.3% of all hospitalizations. After adjusting for a multitude of patient and hospital related factors, patients who had MV for <96 hours(OR = 67.53,p<0.01) or those who had MV for ≥96 hours(OR = 8.73,p<0.01) were associated with a significantly higher odds for IHM when compared to their counterparts. Patients who had MV for ≥96 hours and those who had ET had a significantly longer LOS in-hospitals(p<0.001). Conclusion In this large cohort of hospitalized adults with SCD patients with ACS, the need for mechanical ventilation predicted higher mortality rates and increased hospital resource utilization. Identification of risk factors

Leptin concentrations and SCD-1 indices in classical homocystinuria: Evidence for the role of sulfur amino acids in the regulation of lipid metabolism.

PubMed

Poloni, Soraia; Spritzer, Poli Mara; Mendes, Roberta H; D'Almeida, Vânia; Castro, Kamila; Sperb-Ludwig, Fernanda; Kugele, Johanna; Tucci, Sara; Blom, Henk J; Schwartz, Ida V D

2017-10-01

We describe body composition, lipid metabolism and Stearoyl-CoA desaturase-1 (SCD-1) indices in patients with classical homocystinuria (HCU). Eleven treated HCU patients and 16 healthy controls were included. Body composition and bone mineral density were assessed by dual X-ray absorptiometry. Sulfur amino acids (SAA) and their derivatives (total homocysteine, cysteine, methionine, S-adenosylmethionine, S-adenosylhomocysteine, and glutathione), lipids (free fatty acids, acylcarnitines, triglycerides and lipoproteins), glucose, insulin, leptin, adiponectin, and isoprostanes were measured in plasma. Insulin resistance was evaluated by HOMA-IR. To estimate liver SCD-1 activity, SCD-16 [16:1(n-7)/16:0] and SCD-18 [18:1(n-9)/18:0] desaturation indices were determined. In HCU patients, SCD-16 index was significantly reduced (p=0.03). A trend of an association of SCD-16 index with cysteine was observed (r=0.624, p=0.054). HCU patients displayed lower lean mass (p<0.05), with no differences in fat mass percentage. Leptin and low-density lipoprotein concentrations were lower in HCU patients (p<0.05). Femur bone mineral density Z-scores were correlated with plasma cysteine (r=0.829; p=0.04) and total homocysteine (r=-0.829; p=0.04) in HCU patients. We report alterations in leptin and SCD-1 in HCU patients. These results agree with previous findings from epidemiologic and animal studies, and support a role for SAA on lipid homeostasis. Copyright © 2017 Elsevier B.V. All rights reserved.

Sickle Cell Disease (SCD)

MedlinePlus

... del paciente Transplant process Diseases treated by transplant Acute myeloid leukemia Adrenoleukodystrophy (ALD) Chronic Lymphocytic Leukemia (CLL) ... SCID) Sickle cell disease (SCD) Wiskott-Aldrich syndrome Acute lymphoblastic leukemia (ALL) Other diseases Treatment decisions Learn ...

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

PubMed

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.

High-performance IR detectors at SCD present and future

NASA Astrophysics Data System (ADS)

Nesher, O.; Klipstein, P. C.

2005-09-01

For over 27 years, SCD has been manufacturing and developing a wide range of high performance infra-red detectors, designed to operate in either the mid-wave (MWIR) or the long-wave (LWIR) atmospheric windows. These detectors have been integrated successfully into many different types of system including missile seekers, Time Delay Integration scanning systems, Hand-Held cameras, Missile Warning Systems and many others. SCD's technology for the MWIR wavelength range is based on its well established 2-D arrays of InSb photodiodes. The arrays are flip-chip bonded to SCD's analogue or digital signal processors, all of which have been designed in-house. The 2-D Focal Plane Array (FPA) detectors have a format of 320×256 elements for a 30 μm pitch and 480×384 or 640×512 elements for a 20 μm pitch. Typical operating temperatures are around 77-85K. Five years ago SCD began to develop a new generation of MWIR detectors based on the epitaxial growth of Antimonide Based Compound Semiconductors (ABCS). This ABCS technology allows band-gap engineering of the detection material which enables higher operating temperatures and multi-spectral detection. This year SCD presented its first prototype FPA from this program, an InAlSb based detector operating at a temperature of 100 K. By the end of this year SCD will introduce the first prototype MWIR detector with a 640×512 element format and a pitch of 15 μm. For the LWIR wave-length range SCD manufactures both linear Hg1-xCdxTe (MCT) detectors with a line of 250 elements and Time Delay and Integration (TDI) detectors with formats of 288×4 and 480×6. Recently, SCD has demonstrated its first prototype un-cooled detector which is based on VOx technology and which has a format of 384×288 elements, a pitch of 25 μm and a typical NETD of 50mK at F/1. In this paper we describe the present technologies and products of SCD and the future evolution of our detectors for the MWIR and LWIR detection.

High-performance IR detectors at SCD present and future

NASA Astrophysics Data System (ADS)

Nesher, O.; Klipstein, P. C.

2006-03-01

For over 27 years, SCD has been manufacturing and developing a wide range of high performance infrared detectors, designed to operate in either the mid-wave (MWIR) or the long-wave (LWIR) atmospheric windows. These detectors have been integrated successfully into many different types of system including missile seekers, time delay integration scanning systems, hand-held cameras, missile warning systems and many others. SCD's technology for the MWIR wavelength range is based on its well established 2D arrays of InSb photodiodes. The arrays are flip-chip bonded to SCD's analogue or digital signal processors, all of which have been designed in-house. The 2D focal plane array (FPA) detectors have a format of 320×256 elements for a 30-μm pitch and 480×384 or 640×512 elements for a 20-μm pitch. Typical operating temperatures are around 77-85 K. Five years ago SCD began to develop a new generation of MWIR detectors based on the epitaxial growth of antimonide based compound semiconductors (ABCS). This ABCS technology allows band-gap engineering of the detection material which enables higher operating temperatures and multi-spectral detection. This year SCD presented its first prototype FPA from this program, an InAlSb based detector operating at a temperature of 100 K. By the end of this year SCD will introduce the first prototype MWIR detector with a 640×512 element format and a pitch of 15 μm. For the LWIR wavelength range SCD manufactures both linear Hg1-xCdxTe (MCT) detectors with a line of 250 elements and time delay and integration (TDI) detectors with formats of 288×4 and 480×6. Recently, SCD has demonstrated its first prototype uncooled detector which is based on VOx technology and which has a format of 384×288 elements, a pitch of 25 μm, and a typical NETD of 50 mK at F/1. In this paper, we describe the present technologies and products of SCD and the future evolution of our detectors for the MWIR and LWIR detection.

Rationale and design of the Pan-African Sudden Cardiac Death survey: the Pan-African SCD study.

PubMed

Bonny, Aimé; Ngantcha, Marcus; Amougou, Sylvie Ndongo; Kane, Adama; Marrakchi, Sonia; Okello, Emmy; Taty, Georges; Gehani, Abdulrrazzak; Diakite, Mamadou; Talle, Mohammed A; Lambiase, Pier D; Houenassi, Martin; Chin, Ashley; Otieno, Harun; Temu, Gloria; Owusu, Isaac Koffi; Karaye, Kamilu M; Awad, Abdalla A M; Winkel, Bo Gregers; Priori, Silvia G

2014-01-01

The estimated rate of sudden cardiac death (SCD) in Western countries ranges from 300,000 to 400,000 annually, which represents 0.36 to 1.28 per 1 000 inhabitants in Europe and the United States. The burden of SCD in Africa is unknown. Our aim is to assess the epidemiology of SCD in Africa. The Pan-Africa SCD study is a prospective, multicentre, community-based registry monitoring all cases of cardiac arrest occurring in victims over 15 years old. We will use the definition of SCD as 'witnessed natural death occurring within one hour of the onset of symptoms' or 'unwitnessed natural death within 24 hours of the onset of symptoms'. After approval from institutional boards, we will record demographic, clinical, electrocardiographic and biological variables of SCD victims (including survivors of cardiac arrest) in several African cities. All deaths occurring in residents of districts of interest will be checked for past medical history, circumstances of death, and autopsy report (if possible). We will also analyse the employment of resuscitation attempts during the time frame of sudden cardiac arrest (SCA) in various patient populations throughout African countries. This study will provide comprehensive, contemporary data on the epidemiology of SCD in Africa and will help in the development of strategies to prevent and manage cardiac arrest in this region of the world.

Sickle Cell Disease in Saudi Arabia: The Phenotype in Adults with the Arab-Indian Haplotype is not Benign

PubMed Central

Alsultan, Abdulrahman; Alabdulaali, Mohammed K.; Griffin, Paula J.; AlSuliman, Ahmed M.; Ghabbour, Hazem A.; Sebastiani, Paola; Albuali, Waleed H.; Al-Ali, Amein K.; Chui, David H.K.; Steinberg, Martin H.

2014-01-01

Summary Sickle cell disease (SCD) in Saudi patients from the Eastern Province is associated with the Arab-Indian (AI) HBB (β-globin gene) haplotype. The phenotype of AI SCD in children was described as benign and was attributed to their high fetal haemoglobin (HbF). We conducted a hospital-based study to assess the pattern of SCD complications in adults. A total of 104 patients with average age of 27 years were enrolled. Ninety-six percent of these patients reported history of painful crisis; 47% had at least one episode of acute chest syndrome, however, only 15% had two or more episodes; symptomatic osteonecrosis was reported in 18%; priapism in 17%; overt stroke in 6%; none had leg ulcers. The majority of patients had persistent splenomegaly and 66% had gallstones. Half of the patients co-inherited α-thalassaemia and about one third had glucose-6-phosphate dehydrogenase deficiency. Higher HbF correlated with higher rate of splenic sequestration but not with other phenotypes. The phenotype of adult patients with AI SCD is not benign despite their relatively high HbF level. This is probably due to the continued decline in HbF level in adults and the heterocellular and variable distribution of HbF amongst F-cells. PMID:24224700

Impact of a dedicated infusion clinic for acute management of adults with sickle cell pain crisis.

PubMed

Lanzkron, Sophie; Carroll, C Patrick; Hill, Peter; David, Mandy; Paul, Nicklaine; Haywood, Carlton

2015-05-01

Most adults with sickle cell disease (SCD) receive care for their acute painful episodes in an emergency department (ED) setting. The purpose of this article is to describe the impact of opening a dedicated treatment center for adults with SCD [Sickle Cell Infusion Clinic (SCIC)] on patient outcomes and on hospital discharges for SCD. Descriptive data including demographics, time to first dose of narcotic, and pain scores were collected on patients presenting to the SCIC and ED. Maryland hospital discharge data were obtained from the Maryland Health Services Cost Review Commission. Analyses were conducted using T tests, χ(2) tests, and simple generalized estimating equation regression models accounting for the clustered nature of observations, as appropriate. There were 3,874 visits to the SCIC by 361 unique patients; 85% of those visits resulted in the patient being sent home. During the same time period, there were 3,408 visits to the ED by 558 unique patients with SCD. The overall admission rate from the ED for these patients was 35.9% but decreased significantly over the time period with a rate of 20% in December 2011. There was a significant decrease in readmissions over time for the entire Baltimore Metro area with the likelihood of readmission decreasing by 7% over time. The SCIC model provides adults with SCD access to high quality care that decreases the need for hospital admission. Further research needs to be done to evaluate the cost effectiveness of this model. © 2015 Wiley Periodicals, Inc.

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

PubMed

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.

sCD44 overexpression increases intraocular pressure and aqueous outflow resistance

PubMed Central

Giovingo, Michael; Nolan, Michael; McCarty, Ryan; Pang, Iok-Hou; Clark, Abbot F.; Beverley, Rachel M.; Schwartz, Steven; Stamer, W. Daniel; Walker, Loyal; Grybauskas, Algis; Skuran, Kevin; Kuprys, Paulius V.; Yue, Beatrice Y.J.T.

2013-01-01

Purpose CD44 plays major roles in multiple physiologic processes. The ectodomain concentration of the CD44 receptor, soluble CD44 (sCD44), is significantly increased in the aqueous humor of primary open-angle glaucoma (POAG). The purpose of this study was to determine if adenoviral constructs of CD44 and isolated 32-kDa sCD44 change intraocular pressure (IOP) in vivo and aqueous outflow resistance in vitro. Methods Adenoviral constructs of human standard CD44 (Ad-CD44S), soluble CD44 (Ad-sCD44), and empty viral cDNA were injected into the vitreous of BALB/cJ mice, followed by serial IOP measurements. Overexpression of CD44S and sCD44 was verified in vitro by enzyme-linked immunosorbent assay (ELISA) and western blot analysis. Anterior segments of porcine eyes were perfused with the isolated sCD44. sCD44-treated human trabecular meshwork (TM) cells and microdissected porcine TM were examined by confocal microscopy and Optiprep density gradient with western blot analysis to determine changes in lipid raft components. Results Intravitreous injection of adenoviral constructs with either Ad-CD44S or Ad-sCD44 vectors caused prolonged ocular hypertension in mice. Eight days after vector injection, Ad-CD44S significantly elevated IOP to 28.3±1.2 mmHg (mean±SEM, n=8; p<0.001); Ad-sCD44 increased IOP to 18.5±2.6 mmHg (n=8; p<0.01), whereas the IOP of uninjected eyes was 12.7±0.2 mmHg (n=16). The IOP elevation lasted more than 50 days. Topical administration of a γ-secretase inhibitor normalized Ad-sCD44-induced elevated IOP. sCD44 levels were significantly elevated in the aqueous humor of Ad-CD44S and Ad-sCD44 eyes versus contralateral uninjected eyes (p<0.01). Anterior segment perfusion of isolated 32-kDa sCD44 significantly decreased aqueous outflow rates. Co-administration of isolated sCD44 and CD44 neutralizing antibody or of γ-secretase inhibitor significantly enhanced flow rates. sCD44-treated human TM cells displayed cross-linked actin network formation

Sickle cell disease in adults: developing an appropriate care plan.

PubMed

Matthie, Nadine; Jenerette, Coretta

2015-10-01

Sickle cell disease (SCD) is primarily characterized by pain. This chronic pain with acute exacerbations is the most common reason for hospital visits, admissions, and readmissions, particularly in young adults (aged 18–39 years). People who present to the hospital for pain crises often report that nurses lack knowledge of SCD and, consequently, they do not provide appropriate, timely care. Because pain episodes often result in hospital admissions, this article highlights prominent issues that staff nurses need to know. Using a review of the literature and case studies, the authors provide recommendations to improve care of adults with SCD. No objective signs of a sickle cell pain crisis exist. Patients react to pain in different ways and use various coping mechanisms in response. Suspected opioid addiction should not affect the provision of nursing care. Pain must be treated appropriately to decrease the potential for prolonged admissions and/or readmissions. Patients are to be acknowledged as experts and collaborated with in developing an appropriate plan of care. Advocacy on behalf of the patient is important for better communication with providers. With this knowledge, nurses will be better equipped to provide the appropriate and timely care required to manage pain crises experienced by individuals living with SCD.

Development of quality indicators for transition from pediatric to adult care in sickle cell disease: A modified Delphi survey of adult providers.

PubMed

Sobota, Amy E; Shah, Nishita; Mack, Jennifer W

2017-06-01

Transition from pediatric to adult care is a vulnerable time for young adults with sickle cell disease (SCD); however, improvements in transition are limited by a lack of quality indicators. The purpose of this study was to establish quality indicators for transition in SCD and to determine the optimal timing between the final pediatric visit and the first adult provider visit. We conducted a modified Delphi survey to reach a consensus on which quality indicators are most important for a successful transition. Our expert panel consisted of members of the Sickle Cell Adult Provider Network. In the first round, the participants ranked a list of quality indicators by importance. In the second round, the participants chose their "top 5" quality indicators in terms of importance and also ranked them on feasibility. The response rates for the two rounds were 68 and 96%, respectively. Nine quality indicators were chosen as "top 5" by a majority of respondents, including communication between pediatric and adult providers, timing of first adult visit, patient self-efficacy, quality of life, and trust with their adult provider. Based on the comments from round 1, respondents were also asked for the optimal timing between leaving pediatric care and entering adult care. Most recommended a first adult visit within 2 months of the final pediatric visit. By using these quality indicators chosen by the majority of respondents, we can better develop and evaluate transition programs for young adults with SCD and improve health outcomes for these vulnerable patients. © 2016 Wiley Periodicals, Inc.

The Serum Levels of the Soluble Factors sCD40L and CXCL1 Are Not Indicative of Endometriosis

PubMed Central

Pateisky, Petra; Pils, Dietmar; Kuessel, Lorenz; Szabo, Ladislaus; Walch, Katharina; Obwegeser, Reinhard; Wenzl, René; Yotova, Iveta

2016-01-01

Endometriosis is a benign but troublesome gynecological condition, characterized by endometrial-like tissue outside the uterine cavity. Lately, the discovery and validation of noninvasive diagnostic biomarkers for endometriosis is one of the main priorities in the field. As the disease elicits a chronic inflammatory reaction, we focused our interest on two factors well known to be involved in inflammation and neoplastic processes, namely, soluble CD40 Ligand and CXCL1, and asked whether differences in the serum levels of sCD40L and CXCL1 in endometriosis patients versus controls can serve as noninvasive disease markers. A total of n = 60 women were included in the study, 31 endometriosis patients and 29 controls, and the serum levels of sCD40L and CXCL1 were measured by enzyme-linked immunosorbent assay. Overall, there were no statistically significant differences in the levels of expression of both sCD40L and CXCL1 between patients and controls. This study adds useful clinical data showing that the serum levels of the soluble factors sCD40L and CXCL1 are not associated with endometriosis and are not suitable as biomarkers for disease diagnosis. However, we found a trend toward lower levels of sCD40L in the deep infiltrating endometriosis subgroup making it a potentially interesting target worth further investigation. PMID:27190986

Effects of DHA-enriched fish oil on monocyte/macrophage activation marker sCD163, asymmetric dimethyl arginine, and insulin resistance in type 2 diabetic patients.

PubMed

Toupchian, Omid; Sotoudeh, Gity; Mansoori, Anahita; Nasli-Esfahani, Ensieh; Djalali, Mahmoud; Keshavarz, Seyyed Ali; Koohdani, Fariba

2016-01-01

The beneficial effects of n-3 polyunsaturated fatty acids on reducing cardiovascular risks are well documented. However, the relative effect on some markers of macrophage activation and vascular function is unclear. The primary objective of this study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil on the marker of monocyte/macrophage activation factor soluble CD163, asymmetric dimethyl arginine (ADMA), and insulin resistance in type 2 diabetic patients. In this double-blind randomized controlled trial, 72 type 2 diabetic patients with an age between 30-70 years and body mass index (BMI) of 18.5 to 40 kg/m(2) were randomly assigned to receive 2.4-g DHA-enriched fish oil or placebo per day for 8 weeks. Anthropometric measurements, biochemical, and body composition analyses were assessed at baseline and end of study. Analysis of covariance (ANCOVA) was conducted by controlling for possible confounders to assess between-group differences. Serum levels of sCD163, triglycerides, waist circumference (WC), and weight to height ratio (WHtR) decreased significantly in the fish oil group when compared with the control group. Serum ADMA concentration decreased in the fish oil group with no significant between-group differences. Controlling for confounders revealed that the differences observed in sCD163, triglycerides, WC, and WHtR remained statistically significant. Short-time fish oil supplementation decreased serum sCD163, triglycerides levels, WC, and WHtR in T2DM patients. Because of the positive relationship between sCD163 levels and some T2DM and obesity-related complications, it seems that DHA can be considered as a key intervention in obesity and T2DM. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The efficacy of the new SCD response compression system in the prevention of venous stasis.

PubMed

Kakkos, S K; Szendro, G; Griffin, M; Daskalopoulou, S S; Nicolaides, A N

2000-11-01

The current commercially available sequential intermittent pneumatic compression device used for the prevention of deep venous thrombosis has a constant cycle of 11 seconds' compression and 60 seconds' deflation. This deflation period ensures that the veins are filled before the subsequent cycle begins. It has been suggested that in some positions (eg, semirecumbent or sitting) and with different patients (eg, those with venous reflux), refilling of the veins may occur much earlier than 60 seconds, and thus a more frequent cycle may be more effective in expelling blood proximally. The aim of the study was to test the effectiveness of a new sequential compression system (the SCD Response Compression System), which has the ability to detect the change in the venous volume and to respond by initiating the subsequent cycle when the veins are substantially full. In an open controlled trial at an academic vascular laboratory, the SCD Response Compression System was tested against the existing SCD Sequel Compression System in 12 healthy volunteers who were in supine, semirecumbent, and sitting positions. The refilling time sensed by the device was compared with that determined from recordings of femoral vein flow velocity by the use of duplex ultrasound scan. The total volume of blood expelled per hour during compression was compared with that produced by the existing SCD system in the same volunteers and positions. The refilling time determined automatically by the SCD Response Compression System varied from 24 to 60 seconds in the subjects tested, demonstrating individual patient variation. The refilling time (mean +/- SD) in the sitting position was 40.6 +/- 10. 0 seconds, which was significantly longer (P <.001) than that measured in the supine and semirecumbent positions, 33.8 +/- 4.1 and 35.6 +/- 4.9 seconds, respectively. There was a linear relationship between the duplex scan-derived refill time (mean of 6 readings per leg) and the SCD Response device

Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis.

PubMed

Head, C Alvin; Swerdlow, Paul; McDade, William A; Joshi, Ratan Mani; Ikuta, Tohru; Cooper, Melanie L; Eckman, James R

2010-10-01

Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in patients with sickle cell disease (SCD). The beneficial therapeutic effects of inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether NO breathing reduces acute VOC pain in adult patients and to study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were enrolled. After randomization but before treatment, five were found to not meet final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm) and nine to placebo (21% O2). Primary outcome was the mean change in pain scores after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both groups had similar baseline VAS pain scores but inhaled NO significantly reduced pain scores compared with placebo (P 5 0.02) at the end of NO inhalation. Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr. Parenteral morphine use was lower in the inhaled NO group, but the difference was not statistically significant.Safety assessments included systolic blood pressure measurements,pulse oximetry readings, concentration of delivered nitrogen dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities was observed.

Sudden cardiac death in adults with congenital heart disease: does QRS-complex fragmentation discriminate in structurally abnormal hearts?

PubMed

Vehmeijer, Jim T; Koyak, Zeliha; Bokma, Jouke P; Budts, Werner; Harris, Louise; Mulder, Barbara J M; de Groot, Joris R

2018-06-01

Sudden cardiac death (SCD) causes a large portion of all mortality in adult congenital heart disease (ACHD) patients. However, identification of high-risk patients remains challenging. Fragmented QRS-complexes (fQRS) are a marker for SCD in patients with acquired heart disease but data in ACHD patients are lacking. We therefore aim to evaluate the prognostic value of fQRS for SCD in ACHD patients. From a multicentre cohort of 25 790 ACHD patients, we included tachyarrhythmic SCD cases (n = 147), and controls (n = 266) matched by age, gender, congenital defect and (surgical) intervention. fQRS was defined as ≥1 discontinuous deflection in narrow QRS-complexes, and ≥2 in wide QRS-complexes (>120 ms), in two contiguous ECG leads. We calculated odds ratios (OR) using univariable and multivariable conditional logistic regression models correcting for impaired systemic ventricular function, heart failure and QRS duration >120 ms. ECGs of 147 SCD cases (65% male, median age of death 34 years) and of 266 controls were assessed. fQRS was present in 51% of cases and 34% of controls (OR 2.0, P = 0.003). In multivariable analysis, fQRS was independently associated with SCD (OR 1.9, P = 0.01). The most common diagnose of SCD cases was tetralogy of Fallot (ToF, 34 cases). In ToF, fQRS was present in 71% of cases vs. 43% of controls (OR for SCD 2.8, P = 0.03). fQRS was independently associated with SCD in ACHD patients in a cohort of SCD patients and matched controls. fQRS may therefore contribute to the decision when evaluating ACHD patients for primary prevention of SCD.

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

PubMed Central

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

Soluble CD14 inhibits contractile function and insulin action in primary adult rat cardiomyocytes.

PubMed

Overhagen, Sabrina; Blumensatt, Marcel; Fahlbusch, Pia; Herzfeld de Wiza, Daniella; Müller, Heidi; Maxhera, Bujar; Akhyari, Payam; Ouwens, D Margriet

2017-02-01

Epicardial adipose tissue (EAT) from patients with type 2 diabetes (T2D) is characterized by monocyte infiltrations and displays an elevated release of the monocyte marker soluble cluster of differentiation 14 (sCD14) versus EAT from patients without T2D. We propose that an increased abundance of sCD14 in EAT from patients with T2D may impair the function and insulin sensitivity of the adjacent cardiomyocytes. To examine this, primary adult rat cardiomyocytes were incubated with increasing concentrations of sCD14 in the presence and absence of the co-receptor lipopolysaccharide (LPS), and analyzed for effects on determinants of contractile function, activation of inflammation signalling and insulin action. Exposing cardiomyocytes to sCD14 increased the phosphorylation of the stress kinases p38 and extracellular-signal regulated kinase (ERK). In contrast, insulin-mediated phosphorylation of Akt on Thr308 and Ser473 was inhibited. Furthermore, sCD14 impaired sarcomere shortening and cytosolic Ca 2+ -fluxes. All responses were concentration-dependent and became significant at 1ng/ml sCD14. LPS, either alone or in complex with sCD14, did not affect contractile function or the activation of stress kinases and insulin signalling pathways. Similar data on protein phosphorylation were obtained when exposing human umbilical vein endothelial cells to sCD14. Finally, pharmacological inhibition of p38 reversed the detrimental effects of sCD14 on contractile function, but not on sCD14-induced insulin resistance. Collectively, these data show that sCD14 impairs the function and insulin sensitivity of cardiomyocytes, suggesting that an enhanced sCD14 release from EAT in patients with T2D may contribute to the pathogenesis of diabetes-related cardiometabolic complications. Copyright © 2016 Elsevier B.V. All rights reserved.

A Biopsychosocial-Spiritual Model of Chronic Pain in Adults with Sickle Cell Disease

PubMed Central

Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

2011-01-01

Chronic pain in adults with sickle cell disease (SCD) is a complex multidimensional experience that includes biological, psychological, sociological, and spiritual factors. To date, three models of pain associated with SCD (i.e., biomedical model; biopsychosocial model for SCD pain; Health Belief Model) are published. The biopsychosocial (BPS) multidimensional approach to chronic pain developed by Turk and Gatchel is a widely used model of chronic pain. However, this model has not been applied to chronic pain associated with SCD. In addition, a spiritual/religious dimension is not included in this model. Because spirituality/religion is central to persons affected by SCD, this dimension needs to be added to any model of chronic pain in adults with SCD. In fact, data from one study suggest that spirituality/religiosity is associated with decreased pain intensity in adults with chronic pain from SCD. A BPS-Spiritual model is proposed for adults with chronic pain from SCD since it embraces the whole person. This model includes the biological, psychological, sociological, and spiritual factors relevant to adults with SCD based on past and current research. The purpose of this paper is to describe an adaptation of Turk and Gatchel’s model of chronic pain for adults with SCD and to summarize research findings that support each component of the revised model (i.e., biological, psychological, sociological, spiritual). The paper concludes with a discussion of implications for the use of this model in research. PMID:24315252

Sensitivity of alternative measures of functioning and wellbeing for adults with sickle cell disease: comparison of PROMIS® to ASCQ-Me℠.

PubMed

Keller, San; Yang, Manshu; Treadwell, Marsha J; Hassell, Kathryn L

2017-06-02

Sickle Cell Disease (SCD) causes profound suffering and decrements in daily functioning. Demand is growing for valid and reliable measures to systematically document these effects, particularly in adults. The Adult Sickle Cell Quality of Life Measurement System, ASCQ-Me℠, was developed for this purpose. ASCQ-Me℠ is one of four measurement systems housed within the Person-Centered Assessment Resource (PCAR), funded by the National Institutes of Health, to support clinical research. To help users select the best of these measures for adults with SCD, we evaluated and compared two PCAR systems: one designed to be "universally applicable" (the Patient-Reported Outcome Measurement Information System, PROMIS®) and one designed specifically for SCD (ASCQ-Me℠). Respondents to PROMIS and ASCQ-Me questions were 490 adults with SCD from seven geographically-disbursed clinics within the US. Data were collected for six ASCQ-Me measures (Emotional Impact, Sleep Impact, Social Impact, Stiffness Impact, Pain Impact, SCD Pain Episode Frequency and Severity) and ten PROMIS measures (Pain Impact, Pain Behavior, Physical Functioning, Anxiety, Depression, Fatigue, Satisfaction with Discretionary Social Activities, Satisfaction with Social Roles, Sleep Disturbance, and Sleep-Related Impairment). Statistical analyses, including analysis of variance and multiple linear regression, were conducted to determine the sensitivity of measures to SCD severity. SCD severity was assessed via a checklist of associated treatments and conditions. For those with the most severe SCD, PROMIS scores showed worse health compared to the general population for nine of ten health domains: the magnitude of the difference ranged 0.5 to 1.1 standard deviation units. The PROMIS domains most severely affected were Physical Functioning and Pain (Impact and Behavior). Significant differences by tertile of the SCD-MHC were shown for most PROMIS short forms and all ASCQ-Me short and fixed forms. In most models

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

PubMed

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.

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

PubMed

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 < .001) and pain (p = .002). Perceived injustice from nurses also was a significant predictor of perceived stress (p < .001) and 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.

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

PubMed

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%, p<0.001). Significantly higher sCD30 levels were recorded in recipients suffering graft loss than the others (73.9±48.8 U/mL vs. 37.3±14.6 U/mL, p<0.001). Compared with those with high sCD30 levels, recipients with low sCD30 levels (<50 U/mL) had much better 6-year graft survival (92.4% vs. 46.6%, p<0.001). Further statistical analysis showed that detrimental effect of de novo HLA antibodies and high 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.

The association of optimism and perceived discrimination with health care utilization in adults with sickle cell disease.

PubMed

Stanton, Michael V; Jonassaint, Charles R; Bartholomew, Frederick B; Edwards, Christopher; Richman, Laura; DeCastro, Laura; Williams, Redford

2010-11-01

We evaluated the effect of perceived discrimination, optimism, and their interaction on health care utilization among African American adults with sickle cell disease (SCD). Measures of optimism and perceived discrimination were obtained in 49 African American SCD patients. Multiple regression analyses controlling for sex and age tested effects of optimism and perceived discrimination on the number of emergency department visits (ED) and number and duration of hospitalizations over the past year. A perceived discrimination-optimism interaction was associated with number of emergency departments visits (b = .29, p = .052), number of hospitalizations (b = .36, p = .019), and duration of hospitalizations (b = .30, p = .045) such that those with high perceived discrimination/high optimism had the greatest health care utilization. African American SCD patients with high perceived discrimination/high optimism had greater health care utilization than patients who reported either low perceived discrimination or low optimism. This study suggests that patient personality and coping styles should be considered when evaluating the effects of stress on SCD-related outcomes.

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

PubMed Central

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

Mechanism-Driven Phase I Translational Study of Trifluoperazine in Adults with Sickle Cell Disease

PubMed Central

Molokie, Robert E.; Wilkie, Diana J.; Wittert, Harriett; Suarez, Marie L.; Yao, Yingwei; Zhao, Zhongsheng; He, Ying; Wang, Zaijie J.

2014-01-01

Recent evidence of neuropathic pain among adults with sickle cell disease (SCD) reveals a need for adjuvant analgesic treatments for these patients. Ca2+/calmodulin protein kinase IIα (CaMKIIα) has a known role in neuropathic pain and trifluoperazine is a potent CaMKIIα inhibitor. The study aim was to determine trifluoperazine's acute effects, primarily on adverse effects and secondarily on pain intensity reduction, in adults with SCD. In a phase I, open-label study of 6 doses of trifluoperazine (0.5, 1, 2, 5, 7.5, 10 mg), we obtained 7-hourly and 24-hour repeated measures of adverse effects, pain intensity, and supplemental opioid analgesics in 18 adults with SCD (18 hemoglobin SS disease, 15 women, average age 35.8 ± 8.9 years, ranged 23-53) each of whom received a single dose. Data were analyzed with descriptive statistics. Subjects reported moderate to severe sedative effects at 7.5 and 10 mg doses, respectively. Eight subjects reported 50% reduction in chronic pain without severe sedation or supplemental opioid analgesics; one of these subjects had dystonia 24.5 hrs after the 10 mg dose. The analgesic effect lasted for at least 24 hrs in 3 subjects. Sedation resolved with caffeine and dystonia resolved with diphenhydramine. Adults with SCD experienced minimal adverse effects at doses under 10 mg. In this molecular mechanism-driven translational study, trifluoperazine shows promise as an analgesic drug that is worthy of further testing in a randomized controlled study of adults with SCD starting at a dose of 1 mg in repeated doses to determine long-term adverse and analgesic effects. PMID:24211787

Presepsin (Scd14) as a Marker of Serious Bacterial Infections in Chemotherapy Induced Severe Neutropenia

PubMed Central

Olad, Elham; Sedighi, Iraj; Mehrvar, Azim; Tashvighi, Maryam; Fallahazad, Vahid; Hedayatiasl, Amirabbas; Esfahani, Hossein

2014-01-01

Objective: Timely detection of serious bacterial infections or prediction of sepsis and death is of paramount importance in neutropenic patients especially in oncology settings. The aim of this study was to determine a rapid and secure predictor of sepsis in severe neutropenic cancer children. Methods: In addition to blood culture, we have evaluated serum soluble CD14 on this role and measured it in 39 neutropenic episodes in Mahak pediatric oncology center from September 2012 to January 2013. Fifteen episodes had positive bacterial cultures and 18 had fever. The mean sCD14 values were compared in the presence or absence of fever, positive blood culture and other clinical conditions. Also, mean levels compared in different white cell counts and different four combination settings of fever and blood culture. Findings: It was statistically higher in febrile episodes, in the presence of oral mucositis, indwelling catheter infection, otitis media, and post toxic epidermal necrolysis sepsis and in instances of death within 15 days. Leukocyte count did not affect sCD14 level and in combinations of fever and blood culture, mean sCD14 values were ranked as follow: febrile culture negatives, febrile culture positives, afebrile culture positives and afebrile culture negatives. Conclusion: Although sCD14 was not sensitive in detection of bacteremia, in the absence of clinically detectable source of infection, it was significantly higher in culture positives. PMID:26019777

Combined Plasma Elevation of CRP, Intestinal-Type Fatty Acid-Binding Protein (I-FABP), and sCD14 Identify Older Patients at High Risk for Health Care-Associated Infections.

PubMed

Paillaud, Elena; Bastuji-Garin, Sylvie; Plonquet, Anne; Foucat, Emile; Fournier, Bénédicte; Boutin, Emmanuelle; Le Thuaut, Aurélie; Levy, Yves; Hue, Sophie

2018-01-16

We hypothesized that low-grade inflammation was driven by microbial translocation and associated with an increased risk of health care-associated infections (HAIs). We included 121 patients aged 75 years or over in this prospective cohort study. High-sensitivity C-reactive protein (hs-CRP), I-FABP, and sCD14-as markers for low-grade inflammation, intestinal epithelial barrier integrity, and monocyte activation, respectively-were measured at admission. HAIs occurred during hospitalization in 62 (51%) patients. Elevated hs-CRP (≥6.02 mg/L, ie, the median) was associated with a significantly higher HAI risk when I-FABP was in the highest quartile (odds ratio [OR], 4; 95% confidence interval [95% CI], 1.39-11.49; p = .010). In patients with hs-CRP elevation and highest-quartile I-FABP, sCD14 elevation (≥0.65 µg/mL, ie, the median) was associated with an 11-fold higher HAI risk (OR, 10.8; 95% CI, 2.28-51.1; p = .003). Multivariate analyses adjusted for invasive procedures and comorbidities did not change the associations linking the three markers to the HAI risk. Increased levels of hs-CRP, I-FABP, and sCD14 may reflect loss of intestinal epithelial barrier integrity with microbial translocation leading to monocyte activation and low-grade inflammation. In our cohort, these markers identified patients at high risk for HAIs. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Safety and Utility of Quantitative Sensory Testing among Adults with Sickle Cell Disease: Indicators of Neuropathic Pain?

PubMed Central

Ezenwa, Miriam O.; Molokie, Robert E.; Wang, Zaijie Jim; Yao, Yingwei; Suarez, Marie L.; Pullum, Cherese; Schlaeger, Judith M.; Fillingim, Roger B.; Wilkie, Diana J.

2014-01-01

Objectives Pain is the hallmark symptom of sickle cell disease (SCD), yet the types of pain that these patients experience, and the underlying mechanisms, have not been well characterized. The study purpose was to determine the safety and utility of a mechanical and thermal quantitative sensory testing (QST) protocol and the feasibility of utilizing neuropathic pain questionnaires among adults with SCD. Methods A convenience sample (N=25, 18 women, mean age 38.5 ± 12.5 [20–58 years]) completed self-report pain and quality-of-life tools. Subjects also underwent testing with the TSA-II NeuroSensory Analyzer and calibrated von Frey microfilaments. Results We found that the QST protocol was safe and did not stimulate a SCD pain crisis. There was evidence of central sensitization (n=15), peripheral sensitization (n=1), a mix of central and peripheral sensitization (n=8), or no sensitization (n=1). The neuropathic pain self-report tools were feasible with evidence of construct validity; 40% of the subjects reported S-LANSS scores that were indicative of neuropathic pain and had evidence of central, peripheral or mixed sensitization. Discussion The QST protocol can be safely conducted in adults with SCD and provides evidence of central or peripheral sensitization, which is consistent with a neuropathic component to SCD pain. These findings are novel, warrant a larger confirmatory study, and indicate the need for normative QST data from African American adults and older adults. PMID:25581383

SCD1 thermal design and test result analysis

NASA Technical Reports Server (NTRS)

Cardoso, Humberto Pontes; Muraoka, Issamu; Mantelli, Marcia Barbosa Henriques; Leite, Rosangela M. G.

1990-01-01

The SCD 01 (Satelite de Coleta de Dados 01) is a spin stabilized low Earth orbit satellite dedicated to the collection and distribution of environmental data. It was completely developed at the Brazilian Institute for Space Research (INPE) and is scheduled to be launched in 1992. The SCD 01 passive thermal control design configuration is presented and the thermal analysis results are compared with the temperatures obtained from a Thermal Balance Test. The correlation between the analytical and experimental results is considered very good. Numerical flight simulations show that the thermal control design can keep all the subsystem temperatures within their specified temperature range.

Stearoyl CoA Desaturase (SCD) Facilitates Proliferation of Prostate Cancer Cells through Enhancement of Androgen Receptor Transactivation

PubMed Central

Kim, Seung-Jin; Choi, Hojung; Park, Sung-Soo; Chang, Chawnshang; Kim, Eungseok

2011-01-01

Stearoyl-CoA desaturase (SCD), the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids, is highly expressed in prostate cancer although the SCD protein has been known to be rapidly turned over by proteolytic cleavage. The present data demonstrate that SCD can promote proliferation of androgen receptor (AR)-positive LNCaP prostate cancer cells and enhance dihydrotestosterone (DHT)-induced AR transcriptional activity, resulting in increased expression of prostatespecific antigen (PSA) and kallikrein-related peptidase 2 (KLK2). Interestingly, among the previously reported SCDderived peptides produced by proteolytic cleavage of SCD, a peptide spanning amino acids 130-162 of SCD (SCDCoRNR) contained the CoRNR box motif (LFLII) and enhanced AR transcriptional activity. In contrast, a mutant SCD-CoRNR in which Leu136 was replaced by Ala had no effect on AR transcriptional activity. Moreover, SCDCoRNR directly interacted with AR and inhibited RIP140 suppression of AR transactivation. Knockdown of the SCD gene by SCD microRNA suppressed AR transactivation with decreased cell proliferation, suggesting that SCD may regulate the proliferation of LNCaP cells via modulation of AR transcriptional activity. Moreover, ectopic expression of SCD in LNCaP cells facilitated LNCaP tumor formation and growth in nude mice. Together, the data indicate that SCD plays a key role in the regulation of AR transcriptional activity in prostate cancer cells. PMID:21331774

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.

PubMed

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 < 0.01) and had better emotional response to SCD (r s  = -0.44, p = 0.01). In a sub-analysis of HbSS patients, perceived benefits of 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

Activated effector and memory T cells contribute to circulating sCD30: potential marker for islet allograft rejection.

PubMed

Saini, D; Ramachandran, S; Nataraju, A; Benshoff, N; Liu, W; Desai, N; Chapman, W; Mohanakumar, T

2008-09-01

T-cell activation up-regulates CD30 resulting in an increase in serum soluble CD30 (sCD30). CD4+ T cells, a major source for sCD30, play a significant role in the pathogenesis of rejection. In this study, sCD30 was measured pre- and posttransplant in mouse islet allograft models and human islet allograft recipients. sCD30 was measured by ELISA in diabetic C57BL/6, CD4Knockout (KO) and CD8KO islet allograft recipients. sCD30 increased significantly prior to rejection (1.8 +/- 1 days) in 80% of allograft recipients. Sensitization with donor splenocytes, or a second graft, further increased sCD30 (282.5 +/- 53.5 for the rejecting first graft vs. 374.6 +/- 129 for the rejecting second graft) prior to rejection suggesting memory CD4+ T cells contribute to sCD30. CD4KO failed to reject islet allograft and did not demonstrate sCD30 increase. CD8KO showed elevated (227 +/- 107) sCD30 (1 day) prior to rejection. High pretransplant sCD30 (>20 U/ml) correlated with poor outcome in human islet allograft recipients. Further, increase in sCD30 posttransplant preceded (3-4 months) loss of islet function. We conclude that sCD30 is released from activated CD4 T cells prior to islet allograft rejection and monitoring sCD30 can be a valuable adjunct in the follow-up of islet transplant recipients.

Systematic literature review and assessment of patient-reported outcome instruments in sickle cell disease.

PubMed

Sarri, Grammati; Bhor, Menaka; Abogunrin, Seye; Farmer, Caroline; Nandal, Savita; Halloway, Rashid; Revicki, Dennis A

2018-05-21

Sickle cell disease (SCD) is a chronic condition associated with high mortality and morbidity. It is characterized by acute clinical symptoms such as painful vaso-occlusive crises, which can impair health-related quality of life (HRQL). This study was conducted to identify validated patient-reported outcome (PRO) instruments for use in future trials of potential treatments for SCD. A systematic literature review (SLR) was performed using MEDLINE and EMBASE to identify United States (US)-based studies published in English between 1997 and 2017 that reported on validated PRO instruments used in randomized controlled trials and real-world settings. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist was used to assess the quality of PRO instruments. The SLR included 21 studies assessing the psychometric properties of 24 PRO instruments. Fifteen of those instruments were developed and validated for adults and 10 for children (one instrument was used in both children and young adults aged up to 21 years). Only five of the 15 adult instruments and three of the 10 pediatric instruments were developed specifically for SCD. For most instruments, there were few or no data on validation conducted in SCD development cohorts. Of the 24 PRO instruments identified, 16 had strong internal reliability (Cronbach's α ≥0.80). There was often insufficient information to assess the content validity, construct validity, responsiveness, or test-retest reliability of the instruments identified for both child and adult populations. No validated PRO instruments measuring caregiver burden in SCD were identified. The evidence on the psychometric properties of PRO instruments was limited. However, the results of this SLR provide key information on such tools to help inform the design of future clinical trials for patients with SCD in the US.

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

PubMed

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.

Arginine methylation promotes translation repression activity of eIF4G-binding protein, Scd6.

PubMed

Poornima, Gopalakrishna; Shah, Shanaya; Vignesh, Venkadasubramanian; Parker, Roy; Rajyaguru, Purusharth I

2016-11-02

Regulation of translation plays a critical role in determining mRNA fate. A new role was recently reported for a subset of RGG-motif proteins in repressing translation initiation by binding eIF4G1. However the signaling mechanism(s) that leads to spatial and temporal regulation of repression activity of RGG-motif proteins remains unknown. Here we report the role of arginine methylation in regulation of repression activity of Scd6, a conserved RGG-motif protein. We demonstrate that Scd6 gets arginine methylated at its RGG-motif and Hmt1 plays an important role in its methylation. We identify specific methylated arginine residues in the Scd6 RGG-motif in vivo We provide evidence that methylation augments Scd6 repression activity. Arginine methylation defective (AMD) mutant of Scd6 rescues the growth defect caused by overexpression of Scd6, a feature of translation repressors in general. Live-cell imaging of the AMD mutant revealed that it is defective in inducing formation of stress granules. Live-cell imaging and pull-down results indicate that it fails to bind eIF4G1 efficiently. Consistent with these results, a strain lacking Hmt1 is also defective in Scd6-eIF4G1 interaction. Our results establish that arginine methylation augments Scd6 repression activity by promoting eIF4G1-binding. We propose that arginine methylation of translation repressors with RGG-motif could be a general modulator of their repression activity. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

PubMed Central

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 (P<0.01) and the High group (P<0.001). In multiviariate, overdispersed Poisson regression analyses, age, 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

Pelican: SCD's 640 × 512/15 μm pitch InSb detector

NASA Astrophysics Data System (ADS)

Oiknine Schlesinger, J.; Calahorra, Z.; Uri, E.; Shick, O.; Fishman, T.; Shtrichman, I.; Sinbar, E.; Nahum, V.; Kahanov, E.; Shlomovich, B.; Hasson, S.; Fishler, N.; Chen, D.; Markovitz, T.

2007-04-01

Over the last decade, SCD has developed and manufactured high quality InSb Focal Plane Arrays (FPAs), that are currently used in different applications worldwide. SCD's production line includes InSb FPAs with mid format (320x256 elements), and large format (640x512 elements), all available in various packaging configurations, including fully integrated Detector-Dewar-Cooler Assemblies (DDCA). Many of SCD's products are fully customized for customers' needs, and are optimized for each application with respect to the weight, power, size, and performance. In 2006, SCD has added to its broad InSb product portfolio the new "Pelican" detector family. All Pelican detectors include a large format 640×512 InSb FPA with 15μm pitch, which is based on the FLIR/Indigo ISC0403 Readout Integrated Circuit (ROIC). Due to its small size, the Pelican FPA fits in any mid format Dewar, enabling upgrading of mid format systems with higher spatial resolution due to its good MTF. This work presents the high performance of Pelican products. As achieved in all SCD's InSb DDC's, the Pelican detectors demonstrate high uniformity and correctability (residual non uniformity less than 0.05% std/DR) and remarkable operability (typically better than 99.9%). The Pelican FPA can be integrated in various DDCA configurations as per application needs, such as light weight, low power and compact form for hand held imagers, or a rigid configuration for environmentally demanding operating and storage conditions.

Perceived Injustice Predicts Stress and Pain in Adults with Sickle Cell Disease

PubMed Central

Molokie, Robert E.; Wilkie, Diana J.; Suarez, Marie L.; Yao, Yingwei

2014-01-01

Background Research evidence shows that perceived injustice is a context-based unfair treatment that has negative influence on health outcomes. Aims We examined the contribution of patients’ perceived injustice regarding interactions with healthcare providers to stress and pain in adults with sickle cell disease (SCD). Design This study was a cross-sectional correlational pilot study. Setting Included in the study were adults with SCD who received their care from a university-affiliated Comprehensive Sickle Cell Clinic. Participants/Subjects 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 Americans (n = 48, 92%) and female (n = 41, 79%). Forty-eight patients (92%) reported having a high school diploma or higher. Methods 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. Results Perceived injustice from doctors was a significant predictor of perceived stress, p<.001 and pain, p=.002. Perceived injustice from nurses also was a significant predictor of perceived stress, p<.001 and 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. Conclusions Findings suggest that perceived injustice was negatively associated with stress and pain in adults with SCD and warrant further investigation in a larger sample. PMID:25439119

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

PubMed

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%; P<0.01), weight <60 kg (weight <60 kg; 53.67±9.45 kg versus weight >60 kg; 59.9±9.41 kg; P<0.008), age <30 years (younger age 29.36±7.9 years versus older age 35.14±8.02 years; P<0.001), lower hemoglobin value (9.38±2,3 g/dL versus 10.33±2.61 g/dL; P<0.04). By logistic regression analysis, age <30 years (age >30 years; OR=0.12 [CI95% 0.03-04]; P<0.001), female gender (male gender; OR=0.17 [0.04-0.64]; P<0.01), weight <60 kg (weight >60 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

SCD1 Inhibition Causes Cancer Cell Death by Depleting Mono-Unsaturated Fatty Acids

PubMed Central

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. PMID:22457791

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

PubMed

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.

AmeriFlux US-SCd Southern California Climate Gradient - Sonoran Desert

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goulden, Mike

This is the AmeriFlux version of the carbon flux data for the site US-SCd Southern California Climate Gradient - Sonoran Desert. Site Description - Half hourly data are available at https://www.ess.uci.edu/~california/. This site is one of six Southern California Climate Gradient flux towers operated along an elevation gradient (sites are US-SCg, US-SCs, US-SCf, US-SCw, US-SCc, US-SCd). This site is a low desert site in Southern California's rain shadow; the climate is extremely dry and hot. The site has experience repeated droughts, with negligible rainfall during several years of the record.

SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPARδ expression in mice[S

PubMed Central

Rogowski, Michael P.; Flowers, Matthew T.; Stamatikos, Alexis D.; Ntambi, James M.; Paton, Chad M.

2013-01-01

Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids. Using muscle overexpression, we sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. Wild-type C57Bl/6 (WT) and SCD1 muscle transgenic (SCD1-Tg) mice were generated, and expression of the SCD1 transgene was restricted to skeletal muscle. SCD1 overexpression was associated with increased triglyceride (TG) content. The fatty acid composition of the muscle revealed a significant increase in polyunsaturated fatty acid (PUFA) content of TG, including linoleate (18:2n6). Untrained SCD1-Tg mice also displayed significantly increased treadmill exercise capacity (WT = 6.6 ± 3 min, Tg = 71.9 ± 9.5 min; P = 0.0009). SCD1-Tg mice had decreased fasting plasma glucose, glucose transporter (GLUT)1 mRNA, fatty acid oxidation, mitochondrial content, and increased peroxisome proliferator-activated receptor (PPAR)δ and Pgc-1 protein expression in skeletal muscle. In vitro studies in C2C12 myocytes revealed that linoleate (18:2n6) and not oleate (18:1n9) caused a 3-fold increase in PPARδ and a 9-fold increase in CPT-1b with a subsequent increase in fat oxidation. The present model suggests that increasing delta-9 desaturase activity of muscle increases metabolic function, exercise capacity, and lipid oxidation likely through increased PUFA content, which increases PPARδ expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated. PMID:23918045

Scd5p and Clathrin Function Are Important for Cortical Actin Organization, Endocytosis, and Localization of Sla2p in Yeast

PubMed Central

Henry, Kenneth R.; D'Hondt, Kathleen; Chang, JiSuk; Newpher, Thomas; Huang, Kristen; Hudson, R. Tod; Riezman, Howard; Lemmon, Sandra K.

2002-01-01

SCD5 was identified as a multicopy suppressor of clathrin HC-deficient yeast. SCD5 is essential, but an scd5-Δ338 mutant, expressing Scd5p with a C-terminal truncation of 338 amino acids, is temperature sensitive for growth. Further studies here demonstrate that scd5-Δ338 affects receptor-mediated and fluid-phase endocytosis and normal actin organization. The scd5-Δ338 mutant contains larger and depolarized cortical actin patches and a prevalence of G-actin bars. scd5-Δ338 also displays synthetic negative genetic interactions with mutations in several other proteins important for cortical actin organization and endocytosis. Moreover, Scd5p colocalizes with cortical actin. Analysis has revealed that clathrin-deficient yeast also have a major defect in cortical actin organization and accumulate G-actin. Overexpression of SCD5 partially suppresses the actin defect of clathrin mutants, whereas combining scd5-Δ338 with a clathrin mutation exacerbates the actin and endocytic phenotypes. Both Scd5p and yeast clathrin physically associate with Sla2p, a homologue of the mammalian huntingtin interacting protein HIP1 and the related HIP1R. Furthermore, Sla2p localization at the cell cortex is dependent on Scd5p and clathrin function. Therefore, Scd5p and clathrin are important for actin organization and endocytosis, and Sla2p may provide a critical link between clathrin and the actin cytoskeleton in yeast, similar to HIP1(R) in animal cells. PMID:12181333

Spondylocostal Dysostosis: A Literature Review and Case Report with Long-Term Follow-Up of a Conservatively Managed Patient

PubMed Central

Crawford, Alvin H.

2018-01-01

Introduction Patients with spondylocostal dysostosis (SCD) have congenital spine and rib deformities associated with frequently severe thoracic insufficiency and respiratory compromise. The literature is largely composed of case reports and small cohorts, and there is little information regarding adults with this condition. In this report, we describe the natural history of a conservatively treated patient and include quality-of-life issues such as childbearing, athletic participation, and occupational selection. Case Presentation We present a patient with SCD who was conservatively treated by a single physician from birth for 31 years. Our patient was capable of a reasonably good quality of life through adulthood, including participation in gymnastics and employment. At age 18, she became pregnant and subsequently terminated the pregnancy due to obstetrical concerns for compromised respiration. She has had intermittent respiratory complaints and occasionally experiences dyspnea with exertion, but this only has limited her during certain activities in the past three years. Currently, she takes naproxen for chronic back pain with periodic exacerbations. Discussion Other cases in the literature have described adult SCD patients who have received nonoperative treatment and achieved a wide range of functional outcomes. This provides some limited evidence to suggest that select patients with SCD may be treated conservatively and achieve a reasonable quality of life. However, close clinical follow-up with these patients is recommended, particularly early on, considering the high rates of infant morbidity and mortality. Chest physiotherapy and early pulmonary care have been associated with favorable outcomes in infancy. Surgery to increase thoracic volume and correct scoliosis has been shown in some cases to improve respiratory function. Treatment depends on the degree of thoracic insufficiency and quality of life. The natural history of SCD remains largely unknown, but

Assessing Error Awareness as a Mediator of the Relationship between Subjective Concerns and Cognitive Performance in Older Adults

PubMed Central

Buckley, Rachel F.; Laming, Gemma; Chen, Li Peng Evelyn; Crole, Alice; Hester, Robert

2016-01-01

Objectives Subjective concerns of cognitive decline (SCD) often manifest in older adults who exhibit objectively normal cognitive functioning. This subjective-objective discrepancy is counter-intuitive when mounting evidence suggests that subjective concerns relate to future clinical progression to Alzheimer’s disease, and so possess the potential to be a sensitive early behavioural marker of disease. In the current study, we aimed to determine whether individual variability in conscious awareness of errors in daily life might mediate this subjective-objective relationship. Methods 67 cognitively-normal older adults underwent cognitive, SCD and mood tests, and an error awareness task. Results Poorer error awareness was not found to mediate a relationship between SCD and objective performance. Furthermore, non-clinical levels of depressive symptomatology were a primary driving factor of SCD and error awareness, and significantly mediated a relationship between the two. Discussion We were unable to show that poorer error awareness mediates SCD and cognitive performance in older adults. Our study does suggest, however, that underlying depressive symptoms influence both poorer error awareness and greater SCD severity. Error awareness is thus not recommended as a proxy for SCD, as reduced levels of error awareness do not seem to be reflected by greater SCD. PMID:27832173

Patient Perspectives on Gene Transfer Therapy for Sickle Cell Disease.

PubMed

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.

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

PubMed Central

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

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

PubMed

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 < 0.01). Within the first year post-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.

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

PubMed

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.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

PubMed

Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda

2017-09-01

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

A Review of the Literature on the Multiple Dimensions of Chronic Pain in Adults with Sickle Cell Disease

PubMed Central

Taylor, Lou Ella V.; Stotts, Nancy A.; Humphreys, Janice; Treadwell, Marsha J.; Miaskowski, Christine

2010-01-01

Sickle cell disease (SCD) is a major healthcare and societal problem that affects millions of people worldwide. In Nigeria, 45,000 to 90,000 babies are born each year with SCD. In the United States, SCD is the most common genetic disorder, affecting more than 80,000 people, the majority of whom are African American. Sickle cell pain is the hallmark feature of SCD. Most of the research on pain from SCD has focused on children with acute pain associated with sickle cell crisis. Consequently, very little is known about the occurrence and characteristics of chronic pain, especially in adults with SCD. Individuals with SCD who experience chronic pain are often underserved and their pain is under-treated. This under-treatment may result in millions of dollars per year spent on emergency room visits, hospitalizations, and lost work productivity. The primary purpose of this literature review was to summarize the findings from studies that evaluated the characteristics of chronic pain in adults with SCD. Each of the studies included in this review was evaluated to determine if it provided data on the following multidimensional characteristics of chronic pain: occurrence, number of pain episodes, duration, pattern, quality, location, intensity, aggravating factors, relieving factors, and impact of pain on function. A secondary purpose was to identify gaps in knowledge and directions for future research on the multiple dimensions of chronic pain in adults with SCD. PMID:20656451

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).

PubMed

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 < 0.0001), with all-cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.62 to 3.54; p < 0.0001), and with a composite of all-cause mortality and appropriate ICD shocks (hazard ratio: 3.03; 95% confidence interval: 2.21 to 4.15; p < 0.0001). RR-NSVT identified on routine ICD 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

Production of Gene-Corrected Adult Beta Globin Protein in Human Erythrocytes Differentiated from Patient iPSCs After Genome Editing of the Sickle Point Mutation.

PubMed

Huang, Xiaosong; Wang, Ying; Yan, Wei; Smith, Cory; Ye, Zhaohui; Wang, Jing; Gao, Yongxing; Mendelsohn, Laurel; Cheng, Linzhao

2015-05-01

Human induced pluripotent stem cells (iPSCs) and genome editing provide a precise way to generate gene-corrected cells for disease modeling and cell therapies. Human iPSCs generated from sickle cell disease (SCD) patients have a homozygous missense point mutation in the HBB gene encoding adult β-globin proteins, and are used as a model system to improve strategies of human gene therapy. We demonstrate that the CRISPR/Cas9 system designer nuclease is much more efficient in stimulating gene targeting of the endogenous HBB locus near the SCD point mutation in human iPSCs than zinc finger nucleases and TALENs. Using a specific guide RNA and Cas9, we readily corrected one allele of the SCD HBB gene in human iPSCs by homologous recombination with a donor DNA template containing the wild-type HBB DNA and a selection cassette that was subsequently removed to avoid possible interference of HBB transcription and translation. We chose targeted iPSC clones that have one corrected and one disrupted SCD allele for erythroid differentiation assays, using an improved xeno-free and feeder-free culture condition we recently established. Erythrocytes from either the corrected or its parental (uncorrected) iPSC line were generated with similar efficiencies. Currently ∼6%-10% of these differentiated erythrocytes indeed lacked nuclei, characteristic of further matured erythrocytes called reticulocytes. We also detected the 16-kDa β-globin protein expressed from the corrected HBB allele in the erythrocytes differentiated from genome-edited iPSCs. Our results represent a significant step toward the clinical applications of genome editing using patient-derived iPSCs to generate disease-free cells for cell and gene therapies. Stem Cells 2015;33:1470-1479. © 2015 AlphaMed Press.

Early elevation of soluble CD14 may help identify trauma patients at high risk for infection.

PubMed

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.

Cortical Recruitment and Nuclear–Cytoplasmic Shuttling of Scd5p, a Protein Phosphatase-1-targeting Protein Involved in Actin Organization and EndocytosisD⃞

PubMed Central

Chang, Ji Suk; Henry, Kenneth; Geli, María Isabel; Lemmon, Sandra K.

2006-01-01

Scd5p regulates endocytosis and cortical actin organization as a targeting subunit for the Ser/Thr protein phosphatase-1 (PP1) in yeast. To identify localization signals in Scd5p required for cell surface recruitment, visualization of GFP-tagged Scd5 truncations and deletions was performed. Scd5p contains a PP1 binding site, a 3-repeat region of 20 amino acids (3R), and a 9-repeat region of 12 amino acids (9R). We found that the 9R is critical for cortical localization of Scd5p, but cortical recruitment is not essential for Scd5p's function in actin organization and endocytosis. We propose that Scd5p can target PP1 to endocytic factors in the cytoplasm that have been disassembled and/or inactivated by phosphorylation. We also found that Scd5p undergoes nuclear-cytoplasmic shuttling in a Crm1p-dependent manner. Scd5p-ΔCT lacking the 9R region and its nuclear export signal (NES) accumulates in the nucleus, causing cortical actin and endocytic defects. Cytoplasmic localization and function of Scd5p-ΔCT is restored by NES addition. However, removal of Scd5p's nuclear localization signal prevents nuclear entry, but endocytosis and actin organization remain relatively normal. These results indicate that nuclear-cytoplasmic shuttling is not required for regulation of Scd5p's cortical function and suggest that Scd5p has an independent nuclear function. PMID:16251346

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

PubMed

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.

Adolescents with Sickle Cell Disease: Self-Efficacy as a Factor in Readiness to Transition from Pediatric to Adult Medical Care

ERIC Educational Resources Information Center

Baum, Dabney

2013-01-01

Adolescents and young adults with sickle cell disease (SCD) must develop self-efficacy and disease-management skills to transition successfully to adult medical care. This quantitative study explored whether self-efficacy, age, and gender were predictive of transition readiness of adolescents with SCD from pediatric to adult medical care.…

Stress, Coping, and Psychological Adjustment of Adults with Sickle Cell Disease.

ERIC Educational Resources Information Center

Thompson, Robert J., Jr.; And Others

1992-01-01

Examined psychological adjustment to sickle cell disease (SCD) among 109 African-American adults. Good psychological adjustment was associated with lower levels of perceived daily stress and stress regarding SCD illness tasks, higher efficacy expectations, less use of palliative coping methods and negative thinking/passive adherence pain-coping…

Development and Production of Array Barrier Detectors at SCD

NASA Astrophysics Data System (ADS)

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.

Sequential compression devices in postoperative urologic patients: an observational trial and survey study on the influence of patient and hospital factors on compliance

PubMed Central

2013-01-01

Background Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. Methods 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. Results Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1–3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. Conclusions Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety. PMID:23578129

Sequential compression devices in postoperative urologic patients: an observational trial and survey study on the influence of patient and hospital factors on compliance.

PubMed

Ritsema, David F; Watson, Jennifer M; Stiteler, Amanda P; Nguyen, Mike M

2013-04-11

Sequential compression devices (SCDs) are commonly used for thromboprophylaxis in postoperative patients but compliance is often poor. We investigated causes for noncompliance, examining both hospital and patient related factors. 100 patients undergoing inpatient urologic surgery were enrolled. All patient had SCD sleeves placed preoperatively. Postoperative observations determined SCD compliance and reasons for non-compliance. Patient demographics, length of stay, inpatient unit type, and surgery type were recorded. At discharge, a patient survey gauged knowledge and attitudes regarding SCDs and bother with SCDs. Statistical analysis was performed to correlate SCD compliance with patient demographics; patient knowledge and attitudes regarding SCDs; and patient self-reported bother with SCDs. Observed overall compliance was 78.6%. The most commonly observed reasons for non-compliance were SCD machines not being initially available on the ward (71% of non-compliant observations on post-operative day 1) and SCD use not being restarted promptly after return to bed (50% of non-compliant observations for entire hospital stay). Mean self-reported bother scores related to SCDs were low, ranging from 1-3 out of 10 for all 12 categories of bother assessed. Patient demographics, knowledge, attitudes and bother with SCD devices were not significantly associated with non-compliance. Patient self-reported bother with SCD devices was low. Hospital factors, including SCD machine availability and timely restarting of devices by nursing staff when a patient returns to bed, played a greater role in SCD non-compliance than patient factors. Identifying and addressing hospital related causes for poor SCD compliance may improve postoperative urologic patient safety.

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.

PubMed

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.

Cardiometabolic risk factors are influenced by Stearoyl-CoA Desaturase (SCD) -1 gene polymorphisms and n-3 polyunsaturated fatty acid supplementation.

PubMed

Rudkowska, Iwona; Julien, Pierre; Couture, Patrick; Lemieux, Simone; Tchernof, André; Barbier, Olivier; Vohl, Marie-Claude

2014-05-01

To determine if single nucleotide polymorphisms (SNPs) in stearoyl-CoA desaturase (SCD)-1 gene that encodes a key enzyme for fatty acid metabolism are associated with the response of cardiometabolic risk factors to n-3 PUFA supplementation. Two hundred and ten subjects completed a 2-week run-in period followed by 6-week supplementation with 5 g of fish oil (1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid). Risk factors were measured pre and post n-3 supplementation. Fatty acid composition of plasma phospholipids was analyzed by GC and the desaturase indices SCD16 (16:1n-7/16:0) and SCD18 (18:1n-9/18:0) were calculated. Genotyping of eight SNPs of the SCD1 gene was performed. N-3 PUFA supplementation decreased plasma triglycerides, as well as SCD16 and SCD18 indices, but increased fasting plasma glucose concentrations. SNPs in SCD1-modified cardiometabolic risk factors pre and post n-3 PUFA supplementation: triglyceride (rs508384, p = 0.0086), IL6 (rs3071, p = 0.0485), C-reactive protein (rs3829160, p = 0.0489), and SCD18 indices (rs2234970, p = 0.0337). A significant interaction effect between the SNP and n-3 PUFA supplementation was also observed for fasting plasma glucose levels (rs508384, p = 0.0262). These results suggest that cardiometabolic risk factors are modulated by genetic variations in the SCD1 gene alone or in combination with n-3 PUFA supplementation. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Positron Emission Tomography With 18F-Fluorodeoxyglucose in Patients With Sickle Cell Acute Chest Syndrome

PubMed Central

de Prost, Nicolas; Sasanelli, Myriam; Deux, Jean-François; Habibi, Anoosha; Razazi, Keyvan; Galactéros, Frédéric; Meignan, Michel; Maître, Bernard; Brun-Buisson, Christian; Itti, Emmanuel; Dessap, Armand Mekontso

2015-01-01

Abstract The acute chest syndrome (ACS) is the main cause of mortality among adult patients with sickle cell disease (SCD). Its pathophysiology is still unclear. Using positron emission tomography (PET) with 18F-fluorodeoxyglucose [18F-fluorodeoxyglucose (18F-FDG)], we explored the relationship between regional lung density and lung metabolism, as a reflection of lung neutrophilic infiltration during ACS. Patients were prospectively enrolled in a single-center study. Dual modality chest PET/computed tomography (CT) scans were performed, with 18F-FDG emission scans for quantification of regional 18F-FDG uptake and CT scans with radiocontrast agent to check for pulmonary artery thrombosis. Regional lung 18F-FDG uptake was quantified in ACS patients and in SCD patients without ACS (SCD non-ACS controls). Maximal (SUVmax) and mean (SUVmean) standardized uptake values were computed. Seventeen patients with ACS (mean age 28.3 ± 6.4 years) were included. None died nor required invasive mechanical ventilation. The main lung opacity on CT scans was lower lobe consolidation. Lungs of patients with ACS exhibited higher SUVmax than those of SCD non-ACS controls (2.5 [2.1–2.9] vs 0.8 [0.6–1.0]; P < 0.0001). Regional SUVmax and SUVmean was higher in lower than in upper lobes of ACS patients (P < 0.001) with a significant correlation between lung density and SUVmax (R2 = 0.78). SUVmean was higher in upper lobes of ACS patients than in lungs of SCD non-ACS controls (P < 0.001). Patients with SUVmax >2.5 had longer intensive care unit (ICU) stay than others (7 [6–11] vs 4 [3–6] days; P = 0.016). Lungs of patients with ACS exhibited higher 18F-FDG uptake than SCD non-ACS controls. Lung apices had normal aeration and lower 18F-FDG uptake than lung bases, but higher 18F-FDG uptake than lungs of SCD non-ACS controls. Patients with higher lung 18F-FDG uptake had longer ICU stay than others. PMID:25950690

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

PubMed

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.

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

PubMed

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.

Hydroxyurea therapy contributes to infertility in adult men with sickle cell disease: a review.

PubMed

DeBaun, Michael R

2014-12-01

Hydroxyurea therapy, a chemotherapeutic agent, is the only US FDA approved therapy for the prevention of vaso-occlusive pain in sickle cell disease (SCD). The National Institutes of Health has sponsored two Phase III randomized, placebo-controlled trials, initially in adults, and subsequently in children with sickle cell anemia (SCA). Despite the overwhelming evidence that hydroxyurea therapy is beneficial to children and adults with SCA, individuals with SCA and their families express reservations about its use, in part because of the concerns about fertility, particularly in men. As adolescent boys with SCD are now expected to reach their reproductive years, a new concern is emerging about the role of hydroxyurea therapy as a barrier to their progeny. This review will systemically evaluate compromised fertility in men with SCD, and the evidence that hydroxyurea therapy is associated with further decreasing fertility in men with SCD.

SCD's uncooled detectors and video engines for a wide-range of applications

NASA Astrophysics Data System (ADS)

Fraenkel, A.; Mizrahi, U.; Bikov, L.; Giladi, A.; Shiloah, N.; Elkind, S.; Kogan, I.; Maayani, S.; Amsterdam, A.; Vaserman, I.; Duman, O.; Hirsh, Y.; Schapiro, F.; Tuito, A.; Ben-Ezra, M.

2011-06-01

Over the last decade SCD has established a state of the art VOx μ-Bolometer product line. Due to its overall advantages this technology is penetrating a large range of systems. In addition to a large variety of detectors, SCD has also recently introduced modular video engines with an open architecture. In this paper we will describe the versatile applications supported by the products based on 17μm pitch: Low SWaP short range systems, mid range systems based on VGA arrays and high-end systems that will utilize the XGA format. These latter systems have the potential to compete with cooled 2nd Gen scanning LWIR arrays, as will be demonstrated by TRM3 system level calculations.

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

PubMed

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

Pilot of the Chronic Disease Self-Management Program (CDSMP) for Adolescents and Young Adults with Sickle Cell Disease

PubMed Central

Crosby, Lori E.; Joffe, Naomi E.; Peugh, James; Ware, Russell E.; Britto, Maria T.

2016-01-01

Purpose This study evaluated the feasibility of a group self-management intervention, the well-established Stanford Chronic Disease Self-Management Program (CDSMP), for adolescents and young adults (AYA) with sickle cell disease (SCD). Methods A total of 22 AYA participants with SCD, ages 16 to 24 years, completed self-efficacy and quality of life (HRQOL) measures before the CDSMP, after, and 3 and 6 months later. Results This AYA cohort showed significant improvements in self-efficacy (primary outcome) after the intervention. Analyses of follow-up data revealed a medium effect of the CDSMP on patient activation 3 months post although this was not sustained. Participants were highly satisfied, but only 64% completed the program. Conclusions This study demonstrates that the CDSMP is acceptable, and has the ability to improve self-efficacy. Additional research is needed to determine feasibility and evaluate health outcomes for AYA with SCD. PMID:27793727

When is the optimal time to screen for Chlamydia in adolescents and young adults with sickle cell disease?

PubMed

Bluett-Mills, Gabriella; Kanter, Julie

2015-02-01

Louisiana has a high rate of chlamydia, an easily identifiable and treatable sexually transmitted disease. Patients with chronic diseases, such as sickle cell disease (SCD) often forgo routine primary care visits. We hypothesized that patients with SCD have an increased percentage of asymptomatic chlamydia compared with a matched population. A retrospective cohort study was performed over a 12-month period on eligible patients with SCD (ages 15-30 years). Patients were screened for asymptomatic chlamydia by urine polymerase chain reaction during comprehensive care visits in the SCD clinic. Thirty-four patients underwent testing during the study period, and 4/34 patients (11.8%) tested positive for chlamydia. State data show a rate of 1791/100 000 (1.8%) among a demographically matched cohort. Patients with SCD had a larger percentage of asymptomatic chlamydia than a demographically matched control population. Patients with SCD should be screened by specialists for chlamydia in addition to undergoing routine primary care evaluations. © The Author(s) 2014.

SCD 02 thermal design

NASA Technical Reports Server (NTRS)

Cardoso, Humberto Pontes

1990-01-01

The Satelite de Coleta de Dados (SCD) 02 (Data Collection Satellite) has the following characteristics: 115 kg weight, octagonal prism shape, 1 m diameter, and 0.67 m height. Its specified orbit is nearly circular, 700 km altitude, is inclined 25 deg with respect to the equator line, and has 100 min period. The electric power is supplied by eight solar panels installed on the lateral sides of the satellite. The equipment is located on the central (both faces) and lower (internal face) panels. The satellite is spin stabilized and its attitude control is such that during its lifetime, the solar aspect angle will vary between 80 and 100 deg with respect to its spin axis. Two critical cases were selected for thermal control design purposes: Hot case (maximum solar constant, solar aspect angle equal to 100 deg, minimum eclipse time and maximum internal heat dissipation); and a passive thermal design concept was achieved and the maximum and minimum equipment operating temperatures were obtained through a 109 node finite difference mathematical model.

The Effect of Sleep Continuity on Pain in Adults with Sickle Cell Disease

PubMed Central

Moscou-Jackson, Gyasi; Finan, Patrick H.; Campbell, Claudia M.; Smyth, Joshua M.; Haythornthwaite, Jennifer A.

2015-01-01

This analysis examined the influence of quantifiable parameters of daily sleep continuity, primarily sleep duration and sleep fragmentation, on daily pain in adults with Sickle Cell Disease (SCD). Seventy-five adults with SCD completed baseline psychosocial measures and daily morning (sleep) and evening (pain) diaries over a three-month period. Mixed-effect modeling was used to examine daily between- and within-subjects effects of sleep continuity parameters on pain, as well as the synergistic effect of sleep fragmentation and sleep duration on pain. Results revealed nights of shorter sleep duration and time in bed, increased fragmentation, and less efficient sleep (relative to one’s own mean) were followed by days of greater pain severity. Further, the analgesic benefit of longer sleep duration was attenuated when sleep fragmentation was elevated. These results suggest that both the separate and combined effects of sleep duration and fragmentation should be considered in evaluating pain in adults with SCD. PMID:25842346

COX-2 and SCD, markers of inflammation and adipogenesis, are related to disease activity in Graves' ophthalmopathy.

PubMed

Vondrichova, Tereza; de Capretz, Annika; Parikh, Hemang; Frenander, Christofer; Asman, Peter; Aberg, Magnus; Groop, Leif; Hallengren, Bengt; Lantz, Mikael

2007-06-01

Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy. The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy. Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes. Clinic of Endocrinology, University Hospital, Malmö, Sweden. Patients in acute severe or in chronic phase of ophthalmopathy. Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac. Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes. A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%. We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.

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.

PubMed

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.

Pilot of the Chronic Disease Self-Management Program for Adolescents and Young Adults With Sickle Cell Disease.

PubMed

Crosby, Lori E; Joffe, Naomi E; Peugh, James; Ware, Russell E; Britto, Maria T

2017-01-01

This study evaluated the feasibility of a group self-management intervention, the well-established Stanford Chronic Disease Self-Management Program (CDSMP), for adolescents and young adults (AYA) with sickle cell disease (SCD). A total of 22 AYA participants with SCD, ages 16-24 years, completed self-efficacy and quality of life measures before the CDSMP, after, and 3 and 6 months later. This AYA cohort showed significant improvements in self-efficacy (primary outcome) after the intervention. Analyses of follow-up data revealed a medium effect of the CDSMP on patient activation 3 months post although this was not sustained. Participants were highly satisfied, but only 64% completed the program. This study demonstrates that the CDSMP is acceptable and has the ability to improve self-efficacy. Additional research is needed to determine feasibility and evaluate health outcomes for AYA with SCD. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Relationship between Surgically Treated Superior Canal Dehiscence Syndrome and Body Mass Index.

PubMed

Jan, Taha A; Cheng, Yew Song; Landegger, Lukas D; Lin, Brian M; Srikanth, Priya; Niesten, Marlien E F; Lee, Daniel J

2017-04-01

Objective Examine the association between body mass index (BMI) and superior canal dehiscence (SCD) among patients who have undergone surgical repair for superior canal dehiscence. Study Design Retrospective comparison study. Setting Neurotology tertiary care center. Subjects and Methods Retrospective review of consecutive adult patients evaluated at our institution for SCD syndrome between November 2006 and August 2015. A control group who underwent imaging within the same period for reasons other than SCD was also included. Patient demographics, weight, and height were examined. We performed multiple subgroup analyses to investigate the relationship of BMI, surgery vs no surgery, and correlation between patient BMI and SCD size. Results Of the 268 patients with SCD, 99 underwent surgery; 96 of these patients had complete medical records and were eligible for inclusion. Eighty-eight patients were noted to have arcuate eminence defects, and the mean BMI of this surgical cohort was 28.09 ± 5.26 kg/m 2 . Nonsurgically treated patients with SCD with available data (n = 94) had a mean BMI of 27.97 ± 6.95 kg/m 2 . A control group of 204 patients who underwent computed tomography for non-SCD-related causes was analyzed, of whom 155 had available data with a mean BMI of 27.91 ± 6.38 kg/m 2 . Conclusion We demonstrate that adult patients who undergo surgery for SCD are not obese (mean BMI <30), and size of dehiscence poorly correlates with BMI. Our observations call into question the proposed theory that patient weight is a risk factor for the development of symptomatic SCD involving the arcuate eminence.

Sudden cardiac death in non-dialysis chronic kidney disease patients.

PubMed

Caravaca, Francisco; Chávez, Edgar; Alvarado, Raúl; García-Pino, Guadalupe; Luna, Enrique

2016-01-01

A relatively high proportion of deaths in dialysis patients occur suddenly and unexpectedly. The incidence of sudden cardiac death (SCD) in non-dialysis advanced chronic kidney disease (CKD) stages has been less well investigated. This study aims to determine the incidence and predictors of SCD in a cohort of 1078 patients with CKD not yet on dialysis. Prospective observational cohort study, which included patients with advanced CKD not yet on dialysis (stage 4-5). The association between baseline variables and SCD was assessed using Cox and competing-risk (Fine and Grey) regression models. Demographic, clinical information, medication use, and baseline biochemical parameters of potential interest were included as covariates. During the study period (median follow-up time 12 months), 210 patients died (19%), and SCD occurred in 34 cases (16% of total deaths). All-cause mortality and SCD incidence rates were 113 (95% CI: 99-128), and 18 (95% CI: 13-26) events per 1000 patients/year, respectively. By Cox regression analysis, covariates significantly associated with SCD were: Age, comorbidity index, and treatment with antiplatelet drugs. This latter covariate showed a beneficial effect over the development of SCD. By competing-risk regression, in which the competing event was non-sudden death from any cause, only age and comorbidity index remained significantly associated with SCD. SCD is relatively common in non-dialysis advanced CKD patients. SCD was closely related to age and comorbidity, and some indirect data from this study suggest that unrecognised or undertreated cardiovascular disease may predispose to a higher risk of SCD. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Glomerular function in sickle cell disease patients during crisis.

PubMed

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 < 0.001) indicating glomerular dysfunction. It improved significantly to 107.75 +/- 30.20mls/min at 4 weeks post-crisis (p < 0.001). There was no significant differences in the mean values of CCr at the end of the study (116.20 +/- 31.43mls/min) compared to the pre-crisis stage (p > 0.05). It is concluded that glomerular dysfunction in SCD patients during crisis is potentially reversible.

Adult emergency department patients with sickle cell pain crisis: a learning collaborative model to improve analgesic management.

PubMed

Tanabe, Paula; Artz, Nicole; Mark Courtney, D; Martinovich, Zoran; Weiss, Kevin B; Zvirbulis, Elena; Hafner, John W

2010-04-01

The objectives were to report the baseline (prior to quality improvement interventions) patient and visit characteristics and analgesic management practices for each site participating in an emergency department (ED) sickle cell learning collaborative. A prospective, multisite longitudinal cohort study in the context of a learning-collaborative model was performed in three midwestern EDs. Each site formed a multidisciplinary team charged with improving analgesic management for patients with sickle cell disease (SCD). Each team developed a nurse-initiated analgesic protocol for SCD patients (implemented after a baseline data collection period of 3.5 months at one site and 10 months at the other two sites). All sites prospectively enrolled adults with an acute pain crisis and SCD. All medical records for patients meeting study criteria were reviewed. Demographic, health services, and analgesic management data were abstracted, including ED visit frequency data, ED disposition, arrival and discharge pain score, and name and route of initial analgesic administered. Ten interviews per quarter per site were conducted with patients within 14 days of their ED discharge, and subjects were queried about the highest level of pain acceptable at discharge. The primary outcome variable was the time to initial analgesic administration. Variable data were described as means and standard deviations (SDs) or medians and interquartile ranges (IQR) for nonnormal data. A total of 155 patients met study criteria (median age = 32 years, IQR = 24-40 years) with a total of 701 ED visits. Eighty-six interviews were conducted. Most patients (71.6%) had between one and three visits to the ED during the study period. However, after removing Site 3 from the analysis because of the short data enrollment period (3.5 months), which influenced the mean number of visits for the entire cohort, 52% of patients had between one and three ED visits over 10 months, 21% had four to nine visits, and 27% had

Role of Scd5, a protein phosphatase-1 targeting protein, in phosphoregulation of Sla1 during endocytosis

PubMed Central

Chi, Richard J.; Torres, Onaidy T.; Segarra, Verónica A.; Lansley, Tanya; Chang, Ji Suk; Newpher, Thomas M.; Lemmon, Sandra K.

2012-01-01

Summary Phosphorylation regulates assembly and disassembly of proteins during endocytosis. In yeast, Prk1 and Ark1 phosphorylate factors after vesicle internalization leading to coat disassembly. Scd5, a protein phosphatase-1 (PP1)-targeting subunit, is proposed to regulate dephosphorylation of Prk1/Ark1 substrates to promote new rounds of endocytosis. In this study we analyzed scd5-PP1Δ2, a mutation causing impaired PP1 binding. scd5-PP1Δ2 caused hyperphosphorylation of several Prk1 endocytic targets. Live-cell imaging of 15 endocytic components in scd5-PP1Δ2 revealed that most factors arriving before the invagination/actin phase of endocytosis had delayed lifetimes. Severely affected were early factors and Sla2 (Hip1R homolog), whose lifetime was extended nearly fourfold. In contrast, the lifetime of Sla1, a Prk1 target, was extended less than twofold, but its cortical recruitment was significantly reduced. Delayed Sla2 dynamics caused by scd5-PP1Δ2 were suppressed by SLA1 overexpression. This was dependent on the LxxQxTG repeats (SR) of Sla1, which are phosphorylated by Prk1 and bind Pan1, another Prk1 target, in the dephosphorylated state. Without the SR, Sla1ΔSR was still recruited to the cell surface, but was less concentrated in cortical patches than Pan1. sla1ΔSR severely impaired endocytic progression, but this was partially suppressed by overexpression of LAS17, suggesting that without the SR region the SH3 region of Sla1 causes constitutive negative regulation of Las17 (WASp). These results demonstrate that Scd5/PP1 is important for recycling Prk1 targets to initiate new rounds of endocytosis and provide new mechanistic information on the role of the Sla1 SR domain in regulating progression to the invagination/actin phase of endocytosis. PMID:22825870

Polymorphisms in genes in the SREBP1 signalling pathway and SCD are associated with milk fatty acid composition in Holstein cattle.

PubMed

Rincon, Gonzalo; Islas-Trejo, Alma; Castillo, Alejandro R; Bauman, Dale E; German, Bruce J; Medrano, Juan F

2012-02-01

Genes in the sterol regulatory element-binding protein-1 (SREBP1) pathway play a central role in regulation of milk fat synthesis, especially the de-novo synthesis of saturated fatty acids. SCD, a SREBP-responsive gene, is the key enzyme in the synthesis of monounsaturated fatty acids in the mammary gland. In the present study, we discovered SNP in candidate genes associated with this signalling pathway and SCD to identify genetic markers that can be used for genetic and metabolically directed selection in cattle. We resequenced six candidate genes in the SREBP1 pathway (SREBP1, SCAP, INSIG1, INSIG2, MBTPS1, MBTPS2) and two genes for SCD (SCD1 and SCD5) and discovered 47 Tag SNP that were used in a marker-trait association study. Milk and blood samples were collected from Holstein cows in their 1st or 2nd parity at 100-150 days of lactation. Individual fatty acids from C4 to C20, saturated fatty acid (SFA) content, monounsaturated fatty acid content, polyunsaturated fatty acid content and desaturase indexes were measured and used to perform the asociation analysis. Polymorphisms in the SCD5 and INSIG2 genes were the most representative markers associated with SFA/unsaturated fatty acid (UFA) ratio in milk. The analysis of desaturation activity determined that markers in the SCD1 and SCD5 genes showed the most significant effects. DGAT1 K232A marker was included in the study to examine the effect of this marker on the variation of milk fatty acids in our Holstein population. The percentage of variance explained by DGAT1 in the analysis was only 6% of SFA/UFA ratio. Milk fat depression was observed in one of the dairy herds and in this particular dairy one SNP in the SREBP1 gene (rs41912290) accounted for 40% of the phenotypic variance. Our results provide detailed SNP information for key genes in the SREBP1 signalling pathway and SCD that can be used to change milk fat composition by marker-assisted breeding to meet consumer demands regarding human health, as well

Risk factors for vitamin D deficiency in sickle cell disease.

PubMed

Han, Jin; Zhang, Xu; Saraf, Santosh L; Gowhari, Michel; Molokie, Robert E; Hassan, Johara; Jain, Shivi; Shah, Binal N; Abbasi, Taimur; Machado, Roberto F; Gordeuk, Victor R

2018-05-16

Vitamin D deficiency (VDD), 25-OHD levels <20 ng/ml, is prevalent among patients with sickle cell disease (SCD) and is linked to acute and chronic pain and bone fracture in this population. There is limited literature regarding VDD-associated risk factors for SCD. We examined potential clinical and genomic parameters associated with VDD in 335 adults with SCD in a cross-sectional study. VDD was present in 65% of adult SCD patients, and 25-OHD levels independently and positively correlated with older age (P < 0·001) and vitamin D supplementation (P < 0·001). 25-OHD levels were higher in SCD patients over 40 years of age compared to the general African-American population. Both lower 25-OHD levels and increased pain frequency were associated with increased expression of SLC6A5 encoding glycine transporter-2 (GlyT2), a protein involved in neuronal pain pathways. Lower 25-OHD levels were also associated with increased expression of CYP3A4, and with decreased expression of GC (also termed DBP) and VDR, three genes involved in vitamin D metabolism. We conclude that vitamin D supplementation should be an almost universal feature of the care of young adults with SCD, and that further research is warranted into genomic factors that regulate vitamin D metabolism in SCD. © 2018 John Wiley & Sons Ltd.

C. elegans anaplastic lymphoma kinase ortholog SCD-2 controls dauer formation by modulating TGF-beta signaling.

PubMed

Reiner, David J; Ailion, Michael; Thomas, James H; Meyer, Barbara J

2008-08-05

Different environmental stimuli, including exposure to dauer pheromone, food deprivation, and high temperature, can induce C. elegans larvae to enter the dauer stage, a developmentally arrested diapause state. Although molecular and cellular pathways responsible for detecting dauer pheromone and temperature have been defined in part, other sensory inputs are poorly understood, as are the mechanisms by which these diverse sensory inputs are integrated to achieve a consistent developmental outcome. In this paper, we analyze a wild C. elegans strain isolated from a desert oasis. Unlike wild-type laboratory strains, the desert strain fails to respond to dauer pheromone at 25 degrees C, but it does respond at higher temperatures, suggesting a unique adaptation to the hot desert environment. We map this defect in dauer response to a mutation in the scd-2 gene, which, we show, encodes the nematode anaplastic lymphoma kinase (ALK) homolog, a proto-oncogene receptor tyrosine kinase. scd-2 acts in a genetic pathway shown here to include the HEN-1 ligand, the RTK adaptor SOC-1, and the MAP kinase SMA-5. The SCD-2 pathway modulates TGF-beta signaling, which mediates the response to dauer pheromone, but SCD-2 might mediate a nonpheromone sensory input, such as food. Our studies identify a new sensory pathway controlling dauer formation and shed light on ALK signaling, integration of signaling pathways, and adaptation to extreme environmental conditions.

Interleukin-1 receptor antagonist, a biomarker of response to anti-TB treatment in HIV/TB co-infected patients.

PubMed

Nouhin, Janin; Pean, Polidy; Madec, Yoann; Chevalier, Mathieu F; Didier, Celine; Borand, Laurence; Blanc, François-Xavier; Scott-Algara, Daniel; Laureillard, Didier; Weiss, Laurence

2017-05-01

Despite the high frequency of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in human immunodeficiency virus (HIV)/TB co-infected patients, no diagnostic test is available. Here, we investigated whether monocyte/macrophage activation markers can predict TB-IRIS occurrence and if they are modulated by anti-TB treatment. Frozen plasma was obtained from 127 HIV/TB co-infected adults naïve for antiretroviral therapy, enrolled in the CAMELIA trial, 36 of whom developed TB-IRIS. Concentrations of IL-1Ra, sCD14, and sCD163 were measured at anti-TB treatment onset (baseline), after 8 weeks of anti-TB treatment and at TB-IRIS time. At baseline, IL-1Ra and sCD14 concentrations were similar in TB-IRIS and non-IRIS patients. sCD163 concentrations, although significantly higher in TB-IRIS patients, did not remain associated with TB-IRIS occurrence in multivariate analysis. At the time of TB-IRIS, patients displayed higher concentrations of IL-1Ra (p = 0.002) and sCD14 (p < 0.001). The most striking result was the significant decrease in IL-1Ra after 8 weeks of anti-TB treatment (median reduction: -63% (p < 0.0001)). None of the biomarkers tested was associated with TB-IRIS occurrence. However, repeated measurement of IL-1Ra could help for the diagnosis of TB-IRIS. The substantial reduction of IL-1Ra under treatment suggests that IL-1Ra could be a surrogate biomarker of anti-TB treatment response in HIV-infected patients. Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

The import of abdominal pain in adults with sickle cell disorder.

PubMed

Akinola, N O; Bolarinwa, R A; Faponle, A F

2009-03-01

The aetiology, clinical correlates and outcome of abdominal pain in Nigerian adults with sickle cell disorder (SCD) have not been extensively reported. To determine the prevalence of abdominal vasoocclusive crisis in sickle cell patients with abdominal pain and their clinical correlates if any. Clinical records of adults with SCD (Hb SS and Hb SC) attending the Haematology Outpatients' Clinic of the Obafemi Awolowo University Teaching Hospitals Complex, Southwest Nigerian, over a ten-year period, were reviewed. Demographic, clinical and laboratory data with respect to abdominal pain were retrieved. Data were analysed using appropriate descriptive and inferential statistics. A total of 154 records (128 Hb SS and 26 Hb SC) were available for assessment. The patients mean ages were 22.5 +/- 7.3 years (Hb SS patients) and 24.2 +/- 9.7 years (Hb SC patients) (p > 0.05). The prevalence of abdominal pain was 39.1% and 30.8% in Hb SS and Hb SC respectively (p > 0.05). Pain was commonly in the epigastrium; dull in 35% Hb SS, but peppery/burning in 37.5% Hb SC. All patients with abdominal vaso-occlusive crisis (VOC) had diffuse/generalised dull abdominal pains. A diagnosis of gastritis/peptic ulcer disease was made in 50% of Hb SC patients and 28% of Hb SS patients. Abdominal VOC was diagnosed in 26% Hb SS, but none in Hb SC patients. The size of the liver or spleen and the haematocrit of Hb SS patients did not correlate with the frequency of abdominal pain generally or abdominal VOC specifically. The prevalence rates and patterns of abdominal pain in Hb SS and Hb SC patients appear similar. Abdominal VOC characterised by diffuse/generalised dull abdominal pain occurred in only Hb SS patients and may be a marker of disease severity in these patients.

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

PubMed

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, p<0.05). Biopsy results were comparable in groups treated with tacrolimus and cyclosporine A. The increasing tendency of sCD30 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

Acute appendicitis in patients with sickle cell disease.

PubMed

Al-Nazer, Mona A; Al-Saeed, Hussain H; Al-Salem, Ahmed H

2003-09-01

Patients with sickle cell disease (SCD) often present with abdominal pain, usually attributed to vaso-occlusive crisis, but not rarely, it may be caused by other surgical conditions. Acute appendicitis although common in patients with SCD, it is rare and has a rapid course with a high incidence of perforation. Over a period of 7 years from 1995 to 2001, only 8 patients with SCD out of 1563 (0.5%) patients with acute appendicitis underwent operation at Qatif Central Hospital, Qatif, Kingdom of Saudi Arabia. Their histological slides were reviewed and the findings were compared to those with sickle cell trait (9 patients) and control group (28 patients). All patients with SCD and in spite of a short duration of symptoms had a moderate to severe inflammation and the vessels were packed with sickle red blood cells (RBCs) except one who had an intact mucosa, extensive transmural hemorrhage and congested blood vessels with sickled RBCs without inflammatory cell infiltrate. The mucosa was intact in only one patient with SCD when compared to 5 (55.6%) in those with sickle cell trait and 6 (21.4%) in the control group and in the majority (87.5%) of those with SCD there were moderate to severe mucosal ulcerations when compared to those with sickle cell trait (44.4%) or controls (64.3%). In patients with SCD, acute appendicitis is rare, and these appendicular changes were a sequelae of blockage of appendiceal vessels by sickled RBCs leading to congestion, edema, and ischemia with subsequent mucosal ulceration and marked inflammatory cell infiltrate.

Opioid management strategy decreases admissions in high-utilizing adults with sickle cell disease.

PubMed

Mager, Amy; Pelot, Kristin; Koch, Kathryn; Miller, Lawrence; Hubler, Collin; Ndifor, Anisah; Coan, Canice; Leonard, Cynthia; Field, Joshua J

A subset of adults with sickle cell disease (SCD) heavily utilizes the emergency department (ED) and hospital. The objective of our study was to determine the efficacy of a multidisciplinary strategy to address unmet needs in highly utilizing adults with SCD. In a prospective study, adults with SCD with ≥10 admissions per year were assessed by a multidisciplinary team for gaps in medical, social, and psychological care. Thereafter, the team decided upon the subject's predominant domain that drove admissions and instituted an interventional plan. All plans included an opioid management strategy. Preintervention and postintervention admission rate, as well as opioid use, was compared. Twelve subjects were enrolled. Median rate of ED and hospital admissions preintervention was 25 per year. The predominant domains identified were social needs (n = 6), psychological disorder (n = 1), and substance use disorder (n = 5). Multifaceted interventional plans were developed to address a wide range of gaps in care, but an opioid management strategy was the only intervention successfully completed. Even so, when the preintervention versus postintervention admission rate was compared, regardless of the domain, there was a 40 percent decline in hospital admissions (p = 0.03). Consistent with the successful implementation of an opioid management plan, the decrease in admissions was accompanied by a 37 percent decrease in intravenous opioid use (p = 0.02) and 10 percent decrease in oral opioid use (p = 0.04). An opioid management strategy, as part of a larger effort to improve care for high-utilizing adults with SCD, decreased rate of admissions and opioid use.

Analysis of the operation of the SCD Response intermittent compression system.

PubMed

Morris, Rh J; Griffiths, H; Woodcock, J P

2002-01-01

The work assessed the performance of the Kendall SCD Response intermittent pneumatic compression system for deep vein thrombosis prophylaxis, which claimed to set its cycle according to the blood flow characteristics of individual patient limbs. A series of tests measured the system response in various situations, including application to the limbs of healthy volunteers, and to false limbs. Practical experimentation and theoretical analysis were used to investigate influences on the system functioning other than blood flow. The system tested did not seem to perform as claimed, being unable to distinguish between real and fake limbs. The intervals between compressions were set to times unrealistic for venous refill, with temperature changes in the cuff the greatest influence on performance. Combining the functions of compression and the measurement of the effects of compression in the same air bladder makes temperature artefacts unavoidable and can cause significant errors in the inter-compression interval.

Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD).

PubMed

Bengtsson, A; Holm, L; Bäck, O; Fransson, J; Scheynius, A

1997-09-01

The immunopathology of AD is still unclear, but evidence for an immune response polarized towards Th2 activity has been provided. The CD30 molecule belongs to the tumour necrosis factor (TNF) receptor family and is expressed on activated T cells with a sustained expression in Th2 cells. This molecule also exists in a soluble form (sCD30). Elevated serum levels of sCD30 have been found in patients with Hodgkin's disease, chronic hepatitis B infection and HIV infection. Studies were undertaken to compare the serum levels of sCD30 in patients with AD (n=49) and healthy non-atopic controls (n=94). The presence of sCD30 was analysed with ELISA. A significantly higher concentration of sCD30 was noted in AD patients, median sCD30 level 29 U/ml (range 1-708 U/ml), compared with healthy non-atopic controls (P<0.001), where the median level was 11 U/ml with a range of 1-1042 U/ml. No correlation was found between sCD30 levels and total serum IgE, or between the AD patients' SCORAD values and concentration of sCD30. sCD30 levels were also analysed in 20 AD patients, which during ketoconazole treatment had improved their clinical scores and reduced their serum IgE and eosinophil cationic protein levels. However, no significant decrease in sCD30 levels was noted after treatment. The results show that patients with AD have elevated levels of sCD30, but without correlation to total serum IgE or disease activity.

A novel selection signature in stearoyl-coenzyme A desaturase (SCD) gene for enhanced milk fat content in Bubalus bubalis.

PubMed

Maryam, J; Babar, M E; Bao, Zhang; Nadeem, A

2016-10-01

Modern molecular interventions are dynamic gears for breeding animals with superior genetic make-up. These scientific efforts lead us toward sustainable dairy herds with improved milk production in terms of yield and quality. Many of candidate genes have been dissected at molecular level, and suitable genetic markers have been identified in cattle, but this work has not been validated in buffaloes so far. Stearoyl-coenzyme A desaturase (SCD) has been a potential candidate gene for fat content of milk. Genomic analysis of SCD revealed a total of six variations that were identified through DNA sequencing of animals with lower and higher butter fat %age. After statistical analysis, genotype AB of p.K158I could be associated (P value <0.0001) with higher milk fat %age (10.5 ± 0.5464). This SNP was validated on larger data set by cleaved amplified polymorphic sequences (CAPS) by using DdeI. To scrutinize the functional consequences of p.K158I, 3D protein structure of SCD was predicted by homology modeling and this variation was found located in the vicinity of functional domain and a part of transmembrane helix of this membrane integrated protein. This is a first report toward genetic screening of SCD gene at molecular level in buffalo. This report illustrates the implication of SCD gene and in particular p.K158I variation, in imparting its effect on milk fat %age, which can be targeted in selection of superior dairy buffaloes.

The Effects of a Single Electronic Music Improvisation Session on the Pain of Adults with Sickle Cell Disease: A Mixed Methods Pilot Study.

PubMed

Rodgers-Melnick, Samuel N; Matthie, Nadine; Jenerette, Coretta; Griest Pell, Tara J; Lane, Deforia; Fu, Pingfu; Margevicius, Seunghee; Little, Jane A

2018-06-07

Adults with sickle cell disease (SCD) experience acute pain that is multidimensional. Despite recent improvements in treatment, pain management remains a significant challenge for these individuals. Music therapy interventions have the potential to address several dimensions of SCD pain, but they require systematic investigation. This study investigated feasibility and preliminary efficacy of a single-session electronic music improvisation with a music therapist to diminish pain intensity and improve pain relief and mood in adults with SCD. Using a three-group mixed methods intervention design, we randomized 60 adults with SCD to standard care plus one of three 20-minute study conditions: 1) electronic music improvisation with a music therapist (MT); 2) recorded music listening (ML); or 3) no intervention (control). Measures of pain intensity (VASPI), pain relief (VASPR), and mood (VASMOOD) were assessed before and after the study conditions, with a subset of MT and ML participants interviewed after measure completion. Compared to control, MT produced significant improvements in VASPI (odds ratio (OR) = 5.12, P = 0.035) and VASMOOD (OR = 11.60, P = 0.005). ML produced significant improvements in VASMOOD compared to control (OR = 5.76, P = 0.040). Qualitatively, there were two prominent themes directly related to music: 1) ML and MT offered many positive and few negative effects; and 2) music therapists provided comfort beyond the music. Preliminary findings were promising and support the need for additional studies evaluating improvisational music therapy interventions for acute pain management in adults with SCD.

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

PubMed Central

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

Microbial translocation contribute to febrile episodes in adults with chemotherapy-induced neutropenia.

PubMed

Wong, Michelle; Barqasho, Babilonia; Ohrmalm, Lars; Tolfvenstam, Thomas; Nowak, Piotr

2013-01-01

In this study we sought to determine the contribution of microbial translocation to febrile episodes with no attributable microbiological cause (Fever of Unknown Origin, FUO) in an adult febrile neutropaenic cohort. Endotoxin concentrations were measured with the chromogenic Limulus Amoebocyte Assay and used as a direct measure of bacterial products whilst soluble CD14 (sCD14), measured with ELISA was selected as an indicator of the early host response to endotoxins. Endotoxin concentrations in this cohort were generally elevated but did not differ with the presentation of fever. Further stratification of the febrile episodes based on the microbiological findings revealed significantly (p = 0.0077) elevated endotoxin concentrations in FUO episodes compared with episodes with documented bacterial and viral findings. sCD14 concentrations were however, elevated in febrile episodes (p = 0.0066) and no association was observed between sCD14 concentration and microbiological findings. However, FUO episodes and episodes with Gram-negative bacteraemia were associated with higher median sCD14 concentrations than episodes with Gram-positive bacteraemia (p = 0.030). In conclusion, our findings suggest that in the absence of microbiological findings, microbial translocation could contribute to febrile episodes in an adult neutropaenic cohort. We further observed an association between prophylactic antibiotic use and increased plasma endotoxin concentrations (p = 0.0212).

Demands and challenges for patients with sickle-cell disease requiring hematopoietic stem cell transplantation in Saudi Arabia.

PubMed

Alsultan, Abdulrahman; Jastaniah, Wasil; Al Afghani, Sameera; Al Bagshi, Muneer H; Nasserullah, Zaki; Al-Suliman, Ahmed M; Alabdulaali, Mohammed K

2016-09-01

Allogeneic HSCT is the only curative treatment for SCD. In this study, we estimated the number of Saudi patients with SCD who are candidates for HSCT. We used the presence of overt stroke, recurrent ACS, and frequent severe pain crisis as indications for HSCT. We calculated the frequencies of these complications among a Saudi SCD cohort of 376 patients with SCD, 250 from SW and 126 from Eastern (E) provinces. We found that 59 (23.6%) of SW patients were transplant candidates compared to 22 (17.4%) from E province. It is estimated that about 61 000 patients with SCD live in Saudi Arabia. Thus, the projected number of Saudi patients with SCD who are candidates for HSCT is 10 536 patients. Of those, 2148 are children. The burden of SCD on HSCT centers in Saudi Arabia is substantial and is difficult currently to meet the demand. We recommend recruiting/training more transplant physicians and nurses, expand current capacity of centers if feasible, and open new transplant centers to make HSCT a practical therapeutic option for patients with severe SCD in Saudi Arabia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Study on solid liquid interface heat transfer of PCM under simultaneous charging and discharging (SCD) in horizontal cylinder annulus

NASA Astrophysics Data System (ADS)

Omojaro, Adebola Peter; Breitkopf, Cornelia

2017-07-01

Heat transfer performance during the simultaneous charging and discharging (SCD) operation process for phase change materials (PCM) contained inside the annulus of concentric horizontal cylinder was investigated. In the experimental set-up, the PCM inside the annulus serves as the heat sink along with an externally imposed forced cooling air. The obtained time wise temperature profile was used to determine the effects of different heat fluxes and the imposed forced convection cooling on the melt fraction values and the transition shift time from the observed conduction to natural convection heat transfer patterns. Furthermore, non-dimensional analysis was presented for the heat transfer at the interface to enable generalizing the result. Comparison of the results show that the SCD operation mode establish the condition that enables much PCM phase transition time and thus longer time of large latent heat transfer effect than the Partial and non simultaneous operations. Analysis results show that the variation of the heat flux for the SCD mode did not change the dominance of the natural convection over conduction heat transfers in the PCM. However, it significantly influences the commencement/transition shift time and melting rate while higher heat fluxes yields melt fraction that was 38-63% more for investigated process time. Variation with different cooling air flow rate shows more influences on the melt fraction than on the mode of heat transfer occurring in the PCM during melting. Available non-SCD modes correlation was shown to be insufficient to accurately predict interface heat transfer for the SCD modes.

Soluble CD14 subtype (sCD14-ST) presepsin in premature and full term critically ill newborns with sepsis and SIRS.

PubMed

Mussap, Michele; Puxeddu, Elisabetta; Puddu, Melania; Ottonello, Giovanni; Coghe, Ferdinando; Comite, Paola; Cibecchini, Francesco; Fanos, Vassilios

2015-12-07

Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3 days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically

Height, weight, body mass index and ocular biometry in patients with sickle cell disease.

PubMed

Osuobeni, Ebi Peter; Okpala, Iheanyi; Williamson, Tom H; Thomas, Peter

2009-03-01

To investigate the effects of physical size on refractive error and the dimensions of optical components in sickle cell disease (SCD). The design was cross sectional. Height and weight of adult patients suffering from SCD were measured, and body mass index (BMI) was calculated. Anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD) and axial length (AL) were measured using A-scan ultrasonography. Corneal radius of curvature (CR) was measured using a keratometer. Non-cycloplegic refractive error was determined subjectively. Subjects with SC genotype were significantly taller than those with SS genotype. In the unadjusted data, height was correlated with VCD [p = 0.02, 0.44 mm deeper per 10 cm increase in height, 95% CI (0.65, 8.25)] and AL [p = 0.03, 0.42 mm longer for every 10 cm increase in height, 95%CI (0.49, 7.99)]. The relationship between height, VCD and AL was absent after adjustment for age, gender, genotype and weight. BMI (kg m(-2)) was correlated with AL/CR ratio in both unadjusted (p = 0.04, -0.10 decrease per 1 kg m(-2), 95% CI (-0.018, -0.001) and adjusted data (p = 0.05, -0.10 decrease per 10 kg m(-2), 95% CI (-0.0189, 0.0001). Refractive error was not related to height, weight or BMI. Physical size does not affect refractive error or optical components in adult patients with SCD.

Adult emergency department patients with sickle cell pain crisis: results from a quality improvement learning collaborative model to improve analgesic management.

PubMed

Tanabe, Paula; Hafner, John W; Martinovich, Zoran; Artz, Nicole

2012-04-01

The aims of this study were to 1) estimate differences in pain management process and patient-reported outcomes, pre- and postimplementation of analgesic protocols for adults with sickle cell disease (SCD), and 2) examine the effects of site and visit frequency on changes in pain scores and time to analgesic. A multicenter, prospective, longitudinal study enrolled patients from three academic medical centers between October 2007 and September 2009. All ED patients 18 years or older with a chief complaint of a sickle cell pain episode were enrolled. Sites formed a SCD quality improvement (QI) team and implemented standard nurse-initiated emergency department (ED) analgesic protocols; outcomes were compared between study periods defined as pre- and postimplementation of protocols. Medical record review was conducted to measure time to administration of initial analgesic, opioids used, route of opioid administration, the change in pain scores from arrival to discharge (negative numbers reflect a decrease in pain scores), and the number of ED visits per individual patient during the study period at each site. On day 7 after the ED visit, a follow-up phone interview was conducted. Patients were queried about their ED pain management using a scale from 1 to 10 (1 = outstanding, 10 = worst). Descriptive statistics are used to report the results. Ordinary least-squares regression models were constructed to measure the effect of time period, site, and number of visits per patient on change in pain score. During the study period, 342 unique patients (57% female, mean ± SD age = 32 ± 11 years) were enrolled and had a total of 2,934 visits. There was no difference in time to administration of the initial analgesic between study periods. Overall, there was a significant decrease in pain scores from arrival to discharge between the pre- and postintervention study periods: the average difference in arrival to discharge pain scores (cm) was greater during the postimplementation

Obstructive Sleep Apnea in Patients with Congenital Long QT Syndrome: Implications for Increased Risk of Sudden Cardiac Death.

PubMed

Shamsuzzaman, Abu S; Somers, Virend K; Knilans, Timothy K; Ackerman, Michael J; Wang, Yu; Amin, Raouf S

2015-07-01

Congenital long QT syndrome (LQTS) is a familial arrhythmogenic cardiac channelopathy characterized by prolonged ventricular repolarization and increased risk of torsades de pointes-mediated syncope, seizures, and sudden cardiac death (SCD). QT prolongation corrected for heart rate (QTc) is an important diagnostic and prognostic feature in LQTS. Obstructive sleep apnea (OSA) has been increasingly implicated in the pathogenesis of cardiovascular disease, including arrhythmias and SCD. We tested the hypothesis that the presence of concomitant OSA in patients with LQTS is associated with increased QT intervals, both during sleep and while awake. Polysomnography with simultaneous overnight 12-lead electrocardiography (ECG) was recorded in 54 patients with congenital LQTS and 67 control subjects. OSA was diagnosed as apnea-hypopnea index (AHI) ≥ 5 events/h for adults and AHI > 1 event/h for children. RR and QT intervals were measured from the 12-lead surface ECG. QTc was determined by the Bazett formula. Respiratory disturbance index, AHI, and arousal index were significantly increased in patients with LQTS and with OSA compared to those without OSA and control subjects. QTc during different sleep stages and while awake was also significantly increased in patients with LQTS and OSA compared to those without OSA. Severity of OSA in patients with LQTS was directly associated with the degree of QTc. The presence and severity of obstructive sleep apnea (OSA) in patients with congenital long QT syndrome (LQTS) is associated with increased QT prolongation corrected for heart rate, which is an important biomarker of sudden cardiac death (SCD). Treatment of OSA in LQTS patients may reduce QT prolongation, thus reducing the risk of LQT-triggered SCD. © 2015 Associated Professional Sleep Societies, LLC.

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.

PubMed

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

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

PubMed

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.

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

PubMed

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 (<6 months) 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.

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

PubMed

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.

Hemoglobin and mean platelet volume predicts diffuse T1-MRI white matter volume decrease in sickle cell disease patients.

PubMed

Choi, Soyoung; Bush, Adam M; Borzage, Matthew T; Joshi, Anand A; Mack, William J; Coates, Thomas D; Leahy, Richard M; Wood, John C

2017-01-01

Sickle cell disease (SCD) is a life-threatening genetic condition. Patients suffer from chronic systemic and cerebral vascular disease that leads to early and cumulative neurological damage. Few studies have quantified the effects of this disease on brain morphometry and even fewer efforts have been devoted to older patients despite the progressive nature of the disease. This study quantifies global and regional brain volumes in adolescent and young adult patients with SCD and racially matched controls with the aim of distinguishing between age related changes associated with normal brain maturation and damage from sickle cell disease. T1 weighted images were acquired on 33 clinically asymptomatic SCD patients (age = 21.3 ± 7.8; F = 18, M = 15) and 32 racially matched control subjects (age = 24.4 ± 7.5; F = 22, M = 10). Exclusion criteria included pregnancy, previous overt stroke, acute chest, or pain crisis hospitalization within one month. All brain volume comparisons were corrected for age and sex. Globally, grey matter volume was not different but white matter volume was 8.1% lower (p = 0.0056) in the right hemisphere and 6.8% (p = 0.0068) in the left hemisphere in SCD patients compared with controls. Multivariate analysis retained hemoglobin (β = 0.33; p = 0.0036), sex (β = 0.35; p = 0.0017) and mean platelet volume (β = 0.27; p = 0.016) as significant factors in the final prediction model for white matter volume for a combined r 2 of 0.37 (p < 0.0001). Lower white matter volume was confined to phylogenetically younger brain regions in the anterior and middle cerebral artery distributions. Our findings suggest that there are diffuse white matter abnormalities in SCD patients, especially in the frontal, parietal and temporal lobes, that are associated with low hemoglobin levels and mean platelet volume. The pattern of brain loss suggests chronic microvascular insufficiency and tissue hypoxia as the causal mechanism

A prospective study of nurse and patient education on compliance with sequential compression devices.

PubMed

Stewart, David; Zalamea, Nia; Waxman, Ken; Schuster, Rob; Bozuk, Michael

2006-10-01

Sequential compression devices (SCD) have become the most common form of prophylaxis against the formation of deep venous thrombosis (DVT) among surgical patients. However, compliance with SCD has traditionally been poor. The aim of this study was to assess the affect of patient and nurse education by surgeons on SCD compliance. This was a prospective study involving a single teaching hospital. Compliance was checked twice daily. The main outcomes were compliance rates with SCD use before and after nurse and patient education. Nurses were not aware of the study. Surgical floors had a history of resident and attending interactions regarding SCD, whereas nonsurgical floors did not. A handout that emphasized SCD importance was also given to patients on surgical units. Before education, surgical units had a compliance rate of 61.5 per cent, whereas nonsurgical units had a 48 per cent compliance rate. This difference was significant (P = 0.014). After nursing and patient education on the busiest surgical floor, compliance rates on the surgical ward increased to 65 per cent, a difference that was not of statistical significance (P = 0.515). A nursing unit's daily experience is the most important factor in their compliance rates with SCD use. Focused nursing lectures and patient education may have incremental value.

Patterns of liver iron accumulation in patients with sickle cell disease and thalassemia with iron overload.

PubMed

Hankins, Jane S; Smeltzer, Matthew P; McCarville, M Beth; Aygun, Banu; Hillenbrand, Claudia M; Ware, Russell E; Onciu, Mihaela

2010-07-01

The rate and pattern of iron deposition and accumulation are important determinants of liver damage in chronically transfused patients. To investigate iron distribution patterns at various tissue iron concentrations, effects of chelation on hepatic iron compartmentalization, and differences between patients with sickle cell disease (SCD) and thalassemia major (TM), we prospectively investigated hepatic histologic and biochemical findings in 44 patients with iron overload (35 SCD and 9 TM). The median hepatic iron content (HIC) in patients with TM and SCD was similar at 12.9 and 10.3 mg Fe/g dry weight, respectively (P = 0.73), but patients with SCD had significantly less hepatic fibrosis and inflammation (P < 0.05), less hepatic injury, and significantly less blood exposure. Patients with SCD had predominantly sinusoidal iron deposition, but hepatocyte iron deposition was observed even at low HIC. Chelated patients had more hepatocyte and portal tract iron than non-chelated ones, but similar sinusoidal iron deposition. These data suggest that iron deposition in patients with SCD generally follows the traditional pattern of transfusional iron overload; however, parenchymal hepatocyte deposition also occurs early and chelation removes iron preferentially from the reticuloendothelium. Pathophysiological and genetic differences affecting iron deposition and accumulation in SCD and TM warrants further investigation.

A post-GWAS confirming the SCD gene associated with milk medium- and long-chain unsaturated fatty acids in Chinese Holstein population.

PubMed

Li, C; Sun, D; Zhang, S; Liu, L; Alim, M A; Zhang, Q

2016-08-01

The stearoyl-CoA desaturase (delta-9-desaturase) gene encodes a key enzyme in the cellular biosynthesis of monounsaturated fatty acids. In our initial genome-wide association study (GWAS) of Chinese Holstein cows, 19 SNPs fell in a 1.8-Mb region (20.3-22.1 Mb) on chromosome 26 underlying the SCD gene and were highly significantly associated with C14:1 or C14 index. The aims of this study were to verify whether the SCD gene has significant genetic effects on milk fatty acid composition in dairy cattle. By resequencing the entire coding region of the bovine SCD gene, a total of six variations were identified, including three coding variations (g.10153G>A, g.10213T>C and g.10329C>T) and three intronic variations (g.6926A>G, g.8646G>A and g.16158G>C). The SNP in exon 3, g.10329C>T, was predicted to result in an amino acid replacement from alanine (GCG) to valine (GTG) in the SCD protein. An association study for 16 milk fatty acids using 346 Chinese Holstein cows with accurate phenotypes and genotypes was performed using the mixed animal model with the proc mixed procedure in sas 9.2. All six detected SNPs were revealed to be associated with six medium- and long-chain unsaturated fatty acids (P = 0.0457 to P < 0.0001), specifically for C14:1 and C14 index (P = 0.0005 to P < 0.0001). Subsequently, strong linkage disequilibrium (D' = 0.88-1.00) was observed among all six SNPs in SCD and the five SNPs (rs41623887, rs109923480, rs42090224, rs42092174 and rs42091426) within the 1.8-Mb region identified in our previous GWAS, indicating that the significant association of the SCD gene with milk fatty acid content traits reduced the observed significant 1.8-Mb chromosome region in GWAS. Haplotype-based analysis revealed significant associations of the haplotypes encompassing the six SCD SNPs and one SNP (rs109923480) in a GWAS with C14:1, C14 index, C16:1 and C16 index (P = 0.0011 to P < 0.0001). In summary, our findings provide replicate evidence for our previous

Serum soluble CD30 in early arthritis: a sign of inflammation but not a predictor of outcome.

PubMed

Savolainen, E; Matinlauri, I; Kautiainen, H; Luosujärvi, R; Kaipiainen-Seppänen, O

2008-01-01

To evaluate serum soluble CD30 levels (sCD30) in an early arthritis series and assess their ability to predict the outcome in patients with rheumatoid arthritis (RA) and undifferentiated arthritis (UA) at one year follow-up. Serum sCD30 levels were measured by ELISA from 92 adult patients with RA and UA at baseline and from 60 adult controls. The patients were followed up for one year in the Kuopio 2000 Arthritis Survey. Receiver operating characteristic (ROC) curves were constructed to determine cut off points of sCD30 in RA and UA that select the inflammatory disease from controls. Sensitivity, specificity and positive likelihood ratio, and their 95 % CIs were calculated for sCD30 levels in RA and UA. Median serum sCD30 levels were higher in RA 25.1 (IQ range 16.3-38.6) IU/ml (p<0.001) and in UA 23.4 (15.4-35.6) IU/ml (p<0.001) than in controls 15.1 (10.7-20.8) IU/ml. No differences were recorded between RA and UA (p=0.840). Serum sCD30 levels at baseline did not predict remission at one year follow-up. Serum sCD30 levels were higher in RA and UA than in controls at baseline but they did not predict remission at one year follow-up in this series.

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

PubMed

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.

Sterculic Oil, a Natural SCD1 Inhibitor, Improves Glucose Tolerance in Obese ob/ob Mice

PubMed Central

Ortinau, Laura C.; Pickering, R. Taylor; Nickelson, Karen J.; Stromsdorfer, Kelly L.; Naik, Chaitasi Y.; Haynes, Rebecca A.; Bauman, Dale E.; Rector, R. Scott; Fritsche, Kevin L.; Perfield, James W.

2012-01-01

Obesity and its metabolic complications are associated with increased expression/activity of stearoyl-CoA desaturase-1 (SCD1), a major regulator of lipid metabolism. Reduction or ablation of this enzyme is associated with an improved metabolic profile and has gained attention as a target for pharmaceutical development. Sterculic oil (SO) is a known inhibitor of SCD1 and may provide a natural approach for treating obesity and/or insulin resistance. The purpose of this study was to evaluate the effects of SO consumption in leptin-deficient ob/ob mice, a model of obesity and insulin resistance. Five-week-old male mice received either an AIN-93G (control) or an AIN-93G diet containing 0.5% SO. After 9 weeks, SO supplementation did not alter food intake or body weight; however, the desaturase indices, a proxy of SCD1 activity, were reduced in liver and adipose tissue of SO-supplemented animals. This reduction was associated with improved glucose and insulin tolerance and attenuated hepatic inflammation in obese ob/ob mice, while no appreciable changes were observed in lean control mice receiving SO. Future studies are needed to better understand the mechanism(s) by which SO is functioning to improve glucose metabolism and to further explore the nutraceutical potential and health implications of SO supplementation. PMID:23209931

Does Sickle Cell Disease Protect Against Diabetes Mellitus?

PubMed Central

Mohamed, Ali A.; Al-Qurashi, Fathia; Whitford, David L.

2015-01-01

Objectives: The co-existence of diabetes mellitus (DM) and sickle cell disease (SCD) is rare. This study aimed to explore whether SCD patients have the same DM prevalence as the general population in a country with a high prevalence of DM. Methods: This cross-sectional study included all SCD adult patients admitted to Salmaniya Medical Complex, Bahrain, between 2003 and 2010 (n = 2,204). A random sample (n = 520) was taken to establish the prevalence of DM. Laboratory records were examined to determine the presence of DM. Results: There were 376 SCD patients with complete records; of these, 24 (6.4%) had DM. The age- and sex-standardised prevalence of DM was 8.3%. Conclusion: While the prevalence of DM in SCD patients in Bahrain was high, it was lower than expected in this population. SCD may have a protective effect towards DM development. However, the impact of these two conditions on vascular diseases suggest a need for screening and aggressive treatment in this population. PMID:25685370

An approach to predict Sudden Cardiac Death (SCD) using time domain and bispectrum features from HRV signal.

PubMed

Houshyarifar, Vahid; Chehel Amirani, Mehdi

2016-08-12

In this paper we present a method to predict Sudden Cardiac Arrest (SCA) with higher order spectral (HOS) and linear (Time) features extracted from heart rate variability (HRV) signal. Predicting the occurrence of SCA is important in order to avoid the probability of Sudden Cardiac Death (SCD). This work is a challenge to predict five minutes before SCA onset. The method consists of four steps: pre-processing, feature extraction, feature reduction, and classification. In the first step, the QRS complexes are detected from the electrocardiogram (ECG) signal and then the HRV signal is extracted. In second step, bispectrum features of HRV signal and time-domain features are obtained. Six features are extracted from bispectrum and two features from time-domain. In the next step, these features are reduced to one feature by the linear discriminant analysis (LDA) technique. Finally, KNN and support vector machine-based classifiers are used to classify the HRV signals. We used two database named, MIT/BIH Sudden Cardiac Death (SCD) Database and Physiobank Normal Sinus Rhythm (NSR). In this work we achieved prediction of SCD occurrence for six minutes before the SCA with the accuracy over 91%.

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

PubMed

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.

Assessment of patient-controlled analgesia versus intermittent opioid therapy to manage sickle-cell disease vaso-occlusive crisis in adult patients.

PubMed

Al-Anazi, Alaa; Al-Swaidan, Lowloa; Al-Ammari, Maha; Al-Debasi, Tariq; Alkatheri, Abdulmalik M; Al-Harbi, Shmeylan; Obaidat, Aiman A; Al-Bekairy, Abdulkareem M

2017-01-01

Vaso-occlusive crisis (VOC) is one of the acute complications of sickle-cell disease (SCD). Treatment mainly relies on hydration and pain control by analgesics. The specific aim of this study was to assess potential health outcomes within the first 72 h of admission between intermittent and patient-controlled analgesia (PCA) by opioids among VOC patients. A retrospective chart review study was conducted to determine SCD patients with VOC. Using the hospital electronic system, the following data were collected: patient's age, gender, blood pressure, heart rate, respiratory rate, oxygen saturation, and pain score on admission and daily for 3 days as well as the cumulative opioid analgesic dose for 72 h which is reported as morphine equivalent. One hundred and seventeen patients were screened over a period of 5 years. Of those, 99 (84.6%) met the study inclusion criteria, and 18 patients (15.4%) were excluded from the study. During the first 72 h of admission, a significant reduction in pain score was observed in patients on intermittent intravenous (IV) administration compared to those in the PCA group ( P < 0.0004) where the mean pain scores were 3 and 5, respectively. The total amount of morphine administered over 72 h of admission was significantly higher in PCA group (777 ± 175 mg) as compared to the intermittent IV administration group (149 ± 74 mg) ( P < 0.000003). Clinically significant hypotension or respiratory depression was not observed in both groups over the 72 h of admission. During the first 72 h of admission, intermittent IV administration of morphine was more effective than PCA infusion in pain control.

Factor V Leiden G1691A and prothrombin G20210A mutations among Palestinian patients with sickle cell disease.

PubMed

Samarah, Fekri; Srour, Mahmoud A

2018-01-01

Vascular thrombosis is an important pathophysiological aspect of sickle cell disease (SCD). This study aimed to investigate the prevalence and clinical impact of factor V Leiden G1691A (FVL) and prothrombin G20210A mutations among Palestinian sickle cell disease (SCD) patients. A total of 117 SCD patients, including 59 patients with sickle cell anemia (SS), 33 patients with sickle β-thalassemia and 25 individuals with sickle cell trait (AS) were studied. The control group consisted of 118 healthy individuals. FVL and prothrombin G20210A mutations were determined by RFLP PCR. Analysis of the clinical history of SCD patients revealed that seven patients have had vascular complications such as ischemic stroke or deep vein thrombosis. In SCD patients, the inheritance of the FVL mutation showed a significantly higher incidence of pain in joints, chest and abdomen as well as regular dependence on blood transfusion compared to SCD with the wild type. Age- and sex-adjusted logistic regression analysis revealed a significant association between FVL and sickle cell anemia with an odds ratio (OR) of 5.6 (95% confidence intervals [CI] of 1.91-39.4, P  = 0.039) in SS patients. However, increased prevalence of the FVL in AS subjects and sickle β-thalassemia patients was not statistically significant compared to controls (OR 3.97, 95% CI 0.51-28.6, P  = 0.17 and OR 3.59, 95% CI 0.35-41.6, P  = 0.26, respectively). The distribution of prothrombin G20210A mutation among SCD patients compared to controls was not significantly different, thus our findings do not support an association of this mutation with SCD. FVL was more prevalent among SS patients compared to controls and it was associated with higher incidence of disease complications among SCD patients.

A Sickle Cell Disease Patient with Severe Tricuspid Regurgitation and Early Developed Pulmonary Hypertension.

PubMed

Vaidya, Gaurang; Sarwar, Muhammad; Sun, Zongxia; Wei, Tiemin; Liu, Kan

2015-01-01

Pulmonary hypertension (PH) worsens the mortality of the patients with sickle cell disease (SCD). The exact mechanism of PH development/progression in SCD, including the role of tricuspid regurgitation (TR), remains unclear. We herein report an unusual SCD case, complicated by chronic thromboembolic disorder, who developed severe TR and an accelerated progression of PH. Tricuspid valve surgery significantly ameliorated the patient's symptoms and reduced hospital readmission. The early detection and management of the reversible disorder accelerating the PH development in SCD patients may alter the clinical course, improve the quality of life, and potentially affect the long-term outcome.

Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) Gene and Metabolic Risk Factors in the EPIC-Potsdam Study

PubMed Central

Arregui, Maria; Buijsse, Brian; Stefan, Norbert; Corella, Dolores; Fisher, Eva; di Giuseppe, Romina; Coltell, Oscar; Knüppel, Sven; Aleksandrova, Krasimira; Joost, Hans-Georg; Boeing, Heiner; Weikert, Cornelia

2012-01-01

Background Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question. Methods In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagging-single nucleotide polymorphisms (rs1502593, rs522951, rs11190480, rs3071, rs3793767, rs10883463 and rs508384) and 5 inferred haplotypes with frequency >5% describing 90.9% of the genotype combinations in our population, on triglycerides, body mass index (BMI), waist circumference (WC), glycated haemoglobin (HbA1c), high-sensitivity C-reactive protein (hs-CRP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT) and fetuin-A. Results No significant associations between any of the SNPs or haplotypes and BMI, WC, fetuin-A and hs-CRP were observed. Associations of rs10883463 with triglycerides, GGT and HbA1c as well as of rs11190480 with ALT activity, were weak and became non-significant after multiple-testing correction. Also associations of the haplotype harbouring the minor allele of rs1502593 with HbA1c levels, the haplotype harbouring the minor alleles of rs11190480 and rs508384 with activity of ALT, and the haplotype harbouring the minor alleles of rs522951, rs10883463 and rs508384 with triglyceride and HbA1C levels and GGT activities did not withstand multiple-testing correction. Conclusion These findings suggest that there are no associations between common variants of SCD1 or its inferred haplotypes and the investigated metabolic risk factors. However, given

Serum sCD163 Levels Are Associated with Type 2 Diabetes Mellitus and Are Influenced by Coffee and Wine Consumption: Results of the Di@bet.es Study

PubMed Central

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M. Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar

2014-01-01

Objective Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. Research Design and Methods This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. Results sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46–2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). Conclusions High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes. PMID:24978196

Serum sCD163 levels are associated with type 2 diabetes mellitus and are influenced by coffee and wine consumption: results of the Di@bet.es study.

PubMed

Rojo-Martínez, Gemma; Maymó-Masip, Elsa; Rodríguez, M Mar; Solano, Esther; Goday, Albert; Soriguer, Federico; Valdés, Sergio; Chaves, Felipe Javier; Delgado, Elías; Colomo, Natalia; Hernández, Pilar; Vendrell, Joan; Chacón, Matilde R

2014-01-01

Serum levels of soluble TNF-like weak inducer of apoptosis (sTWEAK) and its scavenger receptor CD163 (sCD163) have been linked to insulin resistance. We analysed the usefulness of these cytokines as biomarkers of type 2 diabetes in a Spanish cohort, together with their relationship to food consumption in the setting of the Di@bet.es study. This is a cross-sectional, matched case-control study of 514 type 2 diabetes subjects and 517 controls with a Normal Oral Glucose Tolerance Test (NOGTT), using data from the Di@bet.es study. Study variables included clinical and demographic structured survey, food frequency questionnaire and physical examination. Serum concentrations of sTWEAK and sCD163 were measured by ELISA. Linear regression analysis determined which variables were related to sTWEAK and sCD163 levels. Logistic regression analysis was used to estimate odd ratios of presenting type 2 diabetes. sCD163 concentrations and sCD163/sTWEAK ratio were 11.0% and 15.0% higher, respectively, (P<0.001) in type 2 diabetes than in controls. Following adjustment for various confounders, the OR for presenting type 2 diabetes in subjects in the highest vs the lowest tertile of sCD163 was [(OR), 2,01 (95%CI, 1,46-2,97); P for trend <0.001]. Coffee and red wine consumption was negatively associated with serum levels of sCD163 (P = 0.0001 and; P = 0.002 for coffee and red wine intake, respectively). High circulating levels of sCD163 are associated with type 2 diabetes in the Spanish population. The association between coffee and red wine intake and these biomarkers deserves further study to confirm its potential role in type 2 diabetes.

Chart Card: Feasibility of a Tool for Improving Emergency Department Care in Sickle Cell Disease

PubMed Central

Neumayr, Lynne; Pringle, Steven; Giles, Stephen; Quirolo, Keith C.; Paulukonis, Susan; Vichinsky, Elliott P.; Treadwell, Marsha J.

2016-01-01

Background Patients with sickle cell disease (SCD) are concerned with emergency department care, including time to treatment and staff attitudes and knowledge. Providers are concerned about rapid access to patient information and SCD treatment protocols. A software application that stores and retrieves encrypted personal medical information on a plastic credit card–sized Chart Card was designed. Objective To determine the applicability and feasibility of the Chart Card on patient satisfaction with emergency department care and provider accessibility to patient information and care protocols. Methods One-half of 44 adults (aged ~18 years) and 50 children with SCD were randomized to either the Chart Card or usual care. Patient satisfaction was surveyed pre and post implementation of the Chart Card program, and emergency department staff was surveyed about familiarity with SCD treatment protocols. Results Fifty-two percent of patients were female (mean age, 18.8 ± 15.6); 61% had SCD SS. Adults visited an emergency department 4.2 ± 4.0 times in the year prior to enrollment vs 2.7 ± 3.7 (p = .06) visits for children, most commonly for pain. Patient emergency department care ratings of very good or excellent increased from 47% to 66% (p < .05), and ratings of staff knowledge improved. Qualitative data reflected positive comments about patient and staff experiences with the Chart Card. Conclusion Patient satisfaction with emergency department care and efficacy in health care increased post Chart Card implementation. Providers valued immediate access to patient information and SCD treatment guidelines. The technology has potential for application in the treatment of other illnesses in other settings. PMID:21141289

Clinical management of adult sickle-cell disease.

PubMed

Bartolucci, Pablo; Galactéros, Frédéric

2012-05-01

This review provides an overview of the clinical management of sickle-cell disease (SCD) with recently published findings. Unfortunately, negative observations did not confirm the hope that therapies acting on nitric oxide-cyclic GMP signaling, NSAIDs or Gardos channel inhibitor would control SCD vaso-occlusive crises. The safety of hydroxycarbamide was further supported by two observational studies covering 20 years and over 2 years in young children. Concerning the management of chronic visceral complications of SCD, the STOP II trial showed the risk of discontinuing blood exchange transfusion for children with transcranial Doppler-assessed accelerated blood-flow velocities. The French multicenter Etendard study found that only 25% of SCD patients with tricuspid regurgitation velocity (TRV) 2.5 m/s or more on echocardiograms had catheterization-confirmed pulmonary hypertension. However, elevated TRV, regardless of its cause, was associated with higher mortality. Finally, recent results identified new therapeutic strategies for the treatment and prevention of renal dysfunction, priapism and skin ulcers, but prospective studies are needed to confirm those findings. SCD treatment relies on concomitant preventive and curative measures to control its acute and chronic manifestations. Pathophysiologic advances have enabled better management, with new therapeutics highly likely in the near future.

Elevated Serum Levels of sCD30 and IL6 and Detectable IL10 Precede Classical Hodgkin Lymphoma Diagnosis.

PubMed

Levin, Lynn I; Breen, Elizabeth C; Birmann, Brenda M; Batista, Julie L; Magpantay, Larry I; Li, Yuanzhang; Ambinder, Richard F; Mueller, Nancy E; Martínez-Maza, Otoniel

2017-07-01

Background: We investigated whether an immune system environment characterized by elevated serum levels of B-cell activation molecules was associated with the subsequent development of classical Hodgkin lymphoma (cHL). Methods: We measured serum levels of B-cell-stimulatory cytokines, IL6 and IL10, soluble CD30 (sCD30), and total IgE prior to cHL diagnosis in 103 cases and 206 matched controls with archived specimens in the DoD Serum Repository. Results: Prediagnosis serum sCD30 and IL6 levels had strong positive associations with risk of a cHL diagnosis 0 to 1 year prior to diagnosis [sCD30 OR = 5.5; 95% confidence interval (CI), 3.4-9.0; IL6 OR = 4.6; 95% CI, 2.9-7.5] and >1 year to 2 years pre-cHL diagnosis (sCD30 OR = 3.3; 95% CI, 1.6-6.7; IL6 OR = 2.9; 95% CI, 1.3-6.5). We observed similar, albeit not consistently significant positive associations, over 4 or more years preceding diagnosis. We did not observe a clear association with IgE levels. Of note, detectable IL10 levels were significantly associated with Epstein-Barr virus (EBV)-positive cHL cases compared with EBV-negative cases. Conclusion: In this prospective analysis, elevated sCD30 and IL6 levels and detectable IL10 preceded cHL diagnosis. Impact: The associations of these cytokines with cHL risk may reflect the production of these molecules by proliferating nascent cHL tumor cells, or by immune cells responding to their presence, prior to clinical detection. The stable elevation in cHL risk, 4 or more years prediagnosis, also suggests that a B-cell-stimulatory immune system milieu precedes, and may promote, lymphomagenesis. Cancer Epidemiol Biomarkers Prev; 26(7); 1114-23. ©2017 AACR . ©2017 American Association for Cancer Research.

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

PubMed Central

Brandow, Amanda M.; Wandersee, Nancy J.; Dasgupta, Mahua; Hoffmann, Raymond G.; Hillery, Cheryl A.; Stucky, Cheryl L.; Panepinto, Julie A.

2016-01-01

Summary Sickle cell disease (SCD) pain transitions from acute to chronic for unknown reasons. Chronic elevation of the pain neurotransmitter substance P (SP) sensitizes pain nociceptors. We evaluated SP levels in controls and SCD patients during baseline and acute pain and investigated associations between SP and age, gender, pain history, haemolysis and hydroxycarbamide (also termed hydroxyurea) use. Plasma SP levels were measured using enzyme-linked immunosorbent assay. Independent samples t-test compared SP levels between: 1) SCD baseline and controls and 2) SCD baseline and acute pain. Multivariate linear regression determined associations between SP and age, gender, pain history and hydroxycarbamide use. Spearman correlation determined an association between SP and haemolysis. We enrolled 35 African American controls, 25 SCD baseline and 12 SCD pain patients. SCD patients were 7-19 years old. Mean±standard deviation SP level (pg/ml) in SCD baseline was higher than controls (32.4±11.6 vs. 22.9±7.6, P=0.0009). SP in SCD pain was higher than baseline (78.1±43.4 vs. 32.4±11.6, P=0.004). Haemolysis correlated with increased SP: Hb (r=−0.7, P=0.0002), reticulocyte count (r=0.61, P=0.0016), bilirubin (r=0.68, P=0.0216), LDH (r=0.62, P=0.0332), aspartate aminotransferase (r=0.68, P=0.003). Patients taking hydroxycarbamide had increased SP (β=29.2, P=0.007). SP could be a mediator of or marker for pain sensitization in SCD and a biomarker and/or target for novel pain treatment. PMID:27539682

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis

PubMed Central

2011-01-01

Introduction CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. Methods This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. Results Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). Conclusions In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target. PMID:21406105

Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

PubMed

Lorente, Leonardo; Martín, María M; Varo, Nerea; Borreguero-León, Juan María; Solé-Violán, Jordi; Blanquer, José; Labarta, Lorenzo; Díaz, César; Jiménez, Alejandro; Pastor, Eduardo; Belmonte, Felipe; Orbe, Josune; Rodríguez, José A; Gómez-Melini, Eduardo; Ferrer-Agüero, José M; Ferreres, José; Llimiñana, María C; Páramo, José A

2011-03-15

CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

Opioid patient controlled analgesia use during the initial experience with the IMPROVE PCA trial: a phase III analgesic trial for hospitalized sickle cell patients with painful episodes.

PubMed

Dampier, Carlton D; Smith, Wally R; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C; Minniti, Caterina P; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A Kyle; McClish, Donna; McKinlay, Sonja M; Miller, Scott T; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J; Weiner, Debra L

2011-12-01

Opioid analgesics administered by patient-controlled analgesia (PCA)are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations,a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI—higher demand dose with low constant infusion or LDHI—lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents,mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI andin the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage.

Sickle cell crisis in the adult: chest radiographic findings and comparison with pediatric sickle cell disease.

PubMed

Miller, J A; Hinrichs, C R

2001-02-01

With the advent of improved therapy, an increasing proportion of individuals suffering from sickle cell disease (SCD) are surviving into adulthood. In contrast to children, little has been documented concerning the typical radiographic findings in adults presenting with sickle cell crises (SCC). We describe the chest radiographic (CXR) manifestations of adults with SCD presenting in SSC, correlated to hemoglobin (Hb) values, and compare them to those of the pediatric sickle cell population. The chest radiographs of 66 consecutive adults presenting to our emergency department complaining of symptoms consistent with acute SCC were retrospectively reviewed over a 12-month period. The radiographic findings were correlated with admission Hb values and compared with those of 50 children with known SCD presenting with SCC. Chi square analysis revealed no significant difference between the cardiovascular and bony findings in the adults and in those of the pediatric controls (p > 0.08-p > 1.0). However, one important difference in the two cohorts was that upper lobe infiltrates occurred exclusively in the pediatric group (p = 0.06). There was a statistically significant (p < 0.05) difference in cardiovascular and skeletal abnormalities between adults with Hb above and below the mean (8.2 g/dL). The radiographic features of adults presenting in acute SCCs are similar to those of children. Although the chest radiograph is often normal, in decreasing frequency, cardiovascular abnormalities, pneumonia sparing the upper lobes, and aseptic osteonecrosis of the shoulders and spine are not uncommon. There is a significant relationship, however, between cardiovascular abnormalities and Hb levels.

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

PubMed

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 <100 U/ml respectively) and the sensitivity, specificity and accuracy of 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.

HOW WE MANAGE IRON OVERLOAD IN SICKLE CELL PATIENTS

PubMed Central

Coates, Thomas D.; Wood, John C.

2017-01-01

Summary Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging. PMID:28295188

How we manage iron overload in sickle cell patients.

PubMed

Coates, Thomas D; Wood, John C

2017-06-01

Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. As transfusions are used to treat the severe complications of SCD, it remains difficult to distinguish whether organ damage is a consequence of iron overload or is due to the complications treated by transfusion. Better management has resulted in increased survival, but prolonged exposure to iron puts SCD patients at greater risk for iron-related complications that should be treated. The success of chelation therapy is dominated by patient adherence to prescribed treatment; thus, adjustment of drug regimens to increase adherence to treatment is critical. This review will discuss the current biology of iron homeostasis in patients with SCD and how this informs our clinical approach to treatment. We will present the clinical approach to treatment of iron overload at our centre using serial assessment of organ iron by magnetic resonance imaging. © 2017 John Wiley & Sons Ltd.

Opioid Patient Controlled Analgesia (PCA) use during the Initial Experience with the IMPROVE PCA Trial: A Phase III Analgesic Trial for Hospitalized Sickle Cell Patients with Painful Episodes

PubMed Central

Dampier, Carlton D.; Smith, Wally R.; Kim, Hae-Young; Wager, Carrie Greene; Bell, Margaret C.; Minniti, Caterina P.; Keefer, Jeffrey; Hsu, Lewis; Krishnamurti, Lakshmanan; Mack, A. Kyle; McClish, Donna; McKinlay, Sonja M.; Miller, Scott T.; Osunkwo, Ifeyinwa; Seaman, Phillip; Telen, Marilyn J.; Weiner, Debra L.

2015-01-01

Opioid analgesics administered by patient-controlled analgesia (PCA) are frequently used for pain relief in children and adults with sickle cell disease (SCD) hospitalized for persistent vaso-occlusive pain, but optimum opioid dosing is not known. To better define PCA dosing recommendations, a multi-center phase III clinical trial was conducted comparing two alternative opioid PCA dosing strategies (HDLI-higher demand dose with low constant infusion or LDHI- lower demand dose and higher constant infusion) in 38 subjects who completed randomization prior to trial closure. Total opioid utilization (morphine equivalents, mg/kg) in 22 adults was 11.6 ± 2.6 and 4.7 ± 0.9 in the HDLI and in the LDHI arms, respectively, and in 12 children it was 3.7 ± 1.0 and 5.8 ± 2.2, respectively. Opioid-related symptoms were mild and similar in both PCA arms (mean daily opioid symptom intensity score: HDLI 0.9 ± 0.1, LDHI 0.9 ± 0.2). The slow enrollment and early study termination limited conclusions regarding superiority of either treatment regimen. This study adds to our understanding of opioid PCA usage in SCD. Future clinical trial protocol designs for opioid PCA may need to consider potential differences between adults and children in PCA usage. PMID:21953763

Chart Card: feasibility of a tool for improving emergency department care in sickle cell disease.

PubMed

Neumayr, Lynne; Pringle, Steven; Giles, Stephen; Quirolo, Keith C; Paulukonis, Susan; Vichinsky, Elliott P; Treadwell, Marsha J

2010-11-01

Patients with sickle cell disease (SCD) are concerned with emergency department care, including time to treatment and staff attitudes and knowledge. Providers are concerned about rapid access to patient information and SCD treatment protocols. A software application that stores and retrieves encrypted personal medical information on a plastic credit card-sized Chart Card was designed. To determine the applicability and feasibility of the Chart Card on patient satisfaction with emergency department care and provider accessibility to patient information and care protocols. One-half of 44 adults (aged -18 years) and 50 children with SCD were randomized to either the Chart Card or usual care. Patient satisfaction was surveyed pre and post implementation of the Chart Card program, and emergency department staff was surveyed about familiarity with SCD treatment protocols. Patient satisfaction with emergency department care and efficacy in health care increased post Chart Card implementation. Providers valued immediate access to patient information and SCD treatment guidelines. The technology has potential for application in the treatment of other illnesses in other settings.

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

PubMed

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.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

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

Shorter survival in adolescent and young adult patients, compared to adult patients, with stage IV colorectal cancer in Japan.

PubMed

Shida, Dai; Ahiko, Yuka; Tanabe, Taro; Yoshida, Takefumi; Tsukamoto, Shunsuke; Ochiai, Hiroki; Takashima, Atsuo; Boku, Narikazu; Kanemitsu, Yukihide

2018-03-27

The incidence of colorectal cancer in adolescent and young adult patients is increasing. However, survival and clinical features of young patients, especially those with stage IV disease, relative to adult patients remain unclear. This retrospective single-institution cohort study was conducted at a tertiary care cancer center. Subjects were 861 consecutive patients who were diagnosed with stage IV colorectal cancer at the age of 15 to 74 years and who were referred to the division of surgery or gastrointestinal oncology at the National Cancer Center Hospital from 1999 to 2013. Overall survival (OS) was investigated and clinicopathological variables were analyzed for prognostic significance. Of these, 66 (8%) were adolescent and young adult patients and 795 (92%) were adult patients. Median survival time was 13.6 months in adolescent and young adult patients and 22.4 months in adult patients, and 5-year OS rates were 17.3% and 20.3%, respectively, indicating significant worse prognosis of adolescent and young adult patients (p = 0.042). However, age itself was not an independent factor associated with prognosis by multivariate analysis. When compared with adult patients, adolescent and young adult patients consisted of higher proportion of the patients who did not undergo resection of primary tumor, which was an independent factor associated with poor prognosis in multivariate analysis. In patients who did not undergo resection (n = 349), OS of adolescent and young adult patients were significantly worse (p = 0.033). Prognoses were worse in adolescent and young adult patients with stage IV colorectal cancer compared to adult patients in Japan, due to a higher proportion of patients who did not undergo resection with more advanced and severe disease, but not due to age itself.

miR-212-5p suppresses lipid accumulation by targeting FAS and SCD1.

PubMed

Guo, Yajie; Yu, Junjie; Wang, Chunxia; Li, Kai; Liu, Bin; Du, Ying; Xiao, Fei; Chen, Shanghai; Guo, Feifan

2017-10-01

MicroRNAs, a class of small noncoding RNAs, are implicated in controlling a variety of biological processes. We have shown that leucine deprivation suppresses lipogenesis by inhibiting fatty acid synthase (FAS) expression in the liver previously; the aim of our current study is to investigate which kind of microRNA is involved in the regulation of FAS expression in response to leucine deprivation. Here, we indicated that microRNA-212-5p specifically binds to mouse FAS 3'UTR and inhibits its activity. Leucine deficiency significantly increased the mRNA levels of miR-212-5p in the livers of mice. Further studies proved that miR-212-5p also directly binds to the 3'UTR of stearoyl-CoA desaturase-1 (SCD1) to inhibit its activity. Overexpression of miR-212-5p decreases the protein levels of FAS and SCD1 in vitro and in vivo , and silencing of miR-212-5p has the opposite effects in mouse primary hepatocytes. Moreover, overexpression of miR-212-5p significantly decreases triglyceride (TG) accumulation in primary hepatocytes and in the livers of mice injected with adenovirus-mediated overexpressing of miR-212-5p (Ad-miR-212). Interestingly, inhibition of miR-212-5p reverses the suppressive effects of leucine deficiency on FAS and SCD1 expression, as well as TG accumulation in mouse primary hepatocytes. Finally, we demonstrate that leucine deficiency induces the expression of miR-212-5p in a GCN2/ATF4-dependent manner. Taken together, our results demonstrate a novel function of hepatic miR-212-5p in the regulation of lipid metabolism which represents a potential therapeutic target for the treatment of non-alcohol fatty liver diseases (NAFLD). © 2017 Society for Endocrinology.

Impaired pubertal development and testicular hormone function in males with sickle cell anemia.

PubMed

Martins, Paulo Roberto Juliano; Kerbauy, José; Moraes-Souza, Helio; Pereira, Gilberto de Araújo; Figueiredo, Maria Stella; Verreschi, Ieda Therezinha

2015-01-01

Changes in weight/height ratio, delayed sexual maturation, hypogonadism and impaired fertility have been demonstrated in sickle cell disease (SCD). This study aimed to evaluate the clinical and laboratory views of the Leydig cells function after stimulation with hCG in adults with sickle cell disease. We studied 15 patients with SCD (18 to 40 years; median=27 years old), fourteen homozygous S, and one with SC disease. The control group, composed by adult males, was divided into two groups: I - 10 relatives (18-39 years, median=26 years) with the same socioeconomic level of the patients, and II - 9 normal individuals (23-28, median=31 years) randomly chosen. Clinically it was observed a slight degree of malnutrition, important puberty delay, rarefaction of chest, underarm and pubic hair, and important reduction of the testis and penis size, featuring a mild hypogonadism in patients with SCD. The hormonal level assessment of testosterone at baseline and at 24, 48 and 72 h after hCG stimulation showed no significant differences between the groups studied. We can presume that adult men with SCD showed clinical hypoandrogenism with normal testicular hormonal function, a fact inconsistent with the hypothesis of primary hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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.

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

PubMed

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.

Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients.

PubMed

Telfer, Paul; Bahal, Nawal; Lo, Alice; Challands, Joanne

2014-07-01

Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial. © 2014 John Wiley & Sons Ltd.

Serum soluble CD163 levels in patients with influenza-associated encephalopathy.

PubMed

Hasegawa, Shunji; Matsushige, Takeshi; Inoue, Hirofumi; Takahara, Midori; Kajimoto, Madoka; Momonaka, Hiroshi; Ishida, Chiemi; Tanaka, Saya; Morishima, Tsuneo; Ichiyama, Takashi

2013-08-01

Influenza-associated encephalopathy (IE) is a serious complication during influenza viral infection. Common clinical symptoms of IE include seizures and progressive coma with high-grade fever. We previously reported that hypercytokinemia and monocyte/macrophage activation may play an important role in the pathogenesis of IE. CD163 is a scavenger receptor for hemoglobin-haptoglobin complexes and is expressed by monocytes/macrophages. Proteolytic cleavage of monocyte-bound CD163 by matrix metalloproteinases releases soluble CD163 (sCD163). However, there have been no reports regarding serum sCD163 levels in IE patients. We measured serum levels of sCD163 as a marker of monocyte/macrophage activation in IE patients with poor outcomes, those without neurological sequelae, influenza patients without IE, and control subjects. Serum sCD163 levels were significantly higher in IE patients with poor outcomes than in those without neurological sequelae. In particular, sCD163 levels in cases of death were significantly higher than those in other cases. Our results suggest that monocyte/macrophage activation is related to the pathogenesis of severe IE. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Elevated Proangiogenic Markers are Associated with Vascular Complications within Ghanaian Sickle Cell Disease Patients.

PubMed

Antwi-Boasiako, Charles; Frimpong, Emmanuel; Gyan, Ben; Kyei-Baafour, Eric; Sey, Fredericka; Dzudzor, Bartholomew; Abdul-Rahman, Mubarak; Dankwah, Gifty B; Otu, Kate H; Ndanu, Tom A; Campbell, Andrew D; Ekem, Ivy; Donkor, Eric S

2018-06-27

: Sickle cell disease (SCD) is an inherited blood disorder that can result in vasculopathy and end organ damage. Angiogenesis has been implicated as a key contributing factor to vascular mediated tissue injury in SCD. The relative plasma levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) greatly influence angiogenesis. Dysregulation of these growth factors, leading to a pro-angiogenic state in SCD patients, has been documented in the developed world but there is very little data in Africa. There is the need, therefore, for studies in Ghanaian SCD patients. The aim of this study was to assess plasma levels of Ang-1, Ang-2, and VEGF in homozygous (HbSS) SCD patients with or without complications and healthy controls (HbAA) in Ghana. The study was a case-control study involving 544 participants: 396 HbSS SCD patients and 148 HbAA healthy controls. The study was conducted at the Center for Clinical Genetics (Sickle Cell Clinic) and Accra Area Blood Centre for National Blood transfusion at the Korle-Bu Teaching Hospital, Accra, Ghana. The plasma levels of Ang-1, Ang-2, and VEGF of study participants were measured with a double sandwich enzyme-linked immunosorbent assay (ELISA) technique. Complete blood count (CBC) was measured with an autoanalyser. The mean plasma Ang-1, Ang-2, and VEGF were significantly higher in HbSS SCD patients with or without complications than healthy controls ( p < 0.001). The Ang-2/Ang-1 ratio was significantly lower in the controls than the HbSS patients ( p < 0.001). The Ang-2/Ang-1 ratio was higher in the HbSS patients with leg ulcers as compared with patients with other complications and healthy controls ( p < 0.001). There were higher leucocyte counts in HbSS patients than healthy controls. Overall, there was elevated plasma levels of Ang-1, Ang-2, and VEGF in SCD patients. The higher Ang-2/Ang-1 plasma levels in patients with leg ulcers suggests a possible ongoing angiogenesis and

Lack of Mucosal Healing From Modified Specific Carbohydrate Diet in Pediatric Patients With Crohn Disease.

PubMed

Wahbeh, Ghassan T; Ward, Brian T; Lee, Dale Y; Giefer, Matthew J; Suskind, David L

2017-09-01

Exclusive enteral nutrition is effective in pediatric Crohn disease but challenging as maintenance therapy. There is interest in food-based therapies such as the specific carbohydrate diet (SCD) but paucity of data on efficacy and effect on mucosal healing, an evolving target of IBD therapy. We conducted a retrospective review of the mucosal healing effect of the SCD in pediatric Crohn disease (CD). The endoscopic findings for children younger than 18 years with CD treated exclusively with the SCD or modified SCD (mSCD; SCD + addition of "illegal foods") were reviewed before and after the diet. Ileocolonoscopic examinations were scored according to the Simple Endoscopic Score for CD and findings on upper endoscopy were described. Seven subjects were identified, all on mSCD. The average age at starting the SCD was 11 ± 3.4 years and median duration of SCD/mSCD therapy was 26 months. All subjects reported no active symptoms before repeat endoscopic evaluation on mSCD, the majority had consistently normal C-reactive protein, albumin and hematocrit assessments, and mildly elevated fecal calprotectin (>50 μg/g, median 201, range 65-312) at any point within 3 months before the repeat endoscopy. One patient showed complete ileocolonic healing but persistent upper gastrointestinal tract ulceration. Complete macroscopic mucosal healing of both the ileocolon and upper gastrointestinal tract was not seen in any patient.

Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

PubMed

Di Cesare, Enrico; Spadaro, Aldo; Ajello, Antonino; Ferraù, Oscar; Alessi, Nunziata; Luigiano, Carmelo; Melluso, Rossana; Freni, Maria A

2005-01-01

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.

Ingestion of Rhus chicken causing systemic contact dermatitis in a Korean patient.

PubMed

Yoo, K H; Seo, S J; Li, K; Hong, C K

2010-10-01

Rhus chicken is a common traditional remedy used to cure gastrointestinal diseases and as a health food in Korea. Unfortunately, systemic contact dermatitis (SCD) due to the ingestion of Rhus occasionally occurs. In this study, the clinical and laboratory findings were reviewed and analysed for 30 Korean patients with SCD developing after ingestion of Rhus chicken. Summer was found to be the commonest period for hospital visits because of this condition. The mean period of incubation for SCD, was 4 ± 1.5 days. The commonest skin features were generalized maculopapular eruptions. Of the 30 patients, 10 had a known history of allergy to Rhus chicken. Many of the patients developed neutrophilia and leucocytosis. All the patients responded well to standard treatments. The commonest reason for their ingestion of Rhus chicken was indigestion. We conclude that SCD often occurs in Koreans after ingestion of Rhus chicken. Patients should be educated about the harmful effects of Rhus chicken and advised not to ingest it.

Soluble CD26 and CD30 plasma levels in HIV infected patients with and without GB virus type C coinfection.

PubMed

Mostafa, Haji-Molla-Hoseini; Ali-Akbar, Pourfathollah; Zahra, Soheili; Minoo, Mohraz; Sedigheh, Amini; Mahnaz, Aghaiepour; Shahram, Samiee; Mahin, Nikoogoftar; Mina, Moghtadaie

2007-06-15

GB virus type C (GBV-C) probably influences HIV infection associated disease by either directly inhibiting HIV replication or enhancing the immune competence to cope with HIV. Still the definitive mechanisms of this inhibitory effect need to be identified. To address the possibility of immune modulating effects of GBV-C coinfection in HIV patients we evaluated plasma levels of soluble (s) CD26 and CD30 in HIV infected patients with and without GBV-C. Cross-sectional comparison of sCD26 and sCD30 levels among 6 HIV/GBV-C coinfected, 11 HIV mono-infected and 13 healthy controls was carried out. We used a commercial EIA to evaluate sCD26 and scD30 and a RT-PCR assay to detect active GBV-C infection. The Mann-Whitney U test was used for statistical analysis. No statistically significant differences were observed in levels of sCD26 and sCD30 in plasma of HIV infected patients with and without GBV-C viremia. GBV-C infection does not appear to influence the sCD26 and sCD30 levels.

The use and effectiveness of complementary and alternative medicine for pain in sickle cell anemia.

PubMed

Majumdar, Suvankar; Thompson, Wendy; Ahmad, Naveed; Gordon, Catherine; Addison, Clifton

2013-11-01

Pain is the clinical hallmark for sickle cell disease (SCD). The objective of this study was to survey the extent and effectiveness of complementary and alternative medicine (CAM) use for pain control among adults with SCD. Of a total of 227 African-American adults with SCD, 208 (92%) admitted to using at least one type of CAM. The three most common types of CAM were prayer (61%), relaxation technique (44%), and massage (35%). Multiple logistic regression showed that marital status was associated with use of relaxation techniques (p = 0.044), and age between 18 and 24 years and at least a high school level of education were associated with use of prayer (p = 0.008 and p = 0.004 respectively). Our study showed that CAM use is common among adult patients with SCD. Further well designed prospective studies are needed to help develop best practices that emphasize an optimized balance of conventional and evidence based CAM therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients.

PubMed

Ellithy, Hend N; Yousri, Sherif; Shahin, Gehan H

2015-12-01

Clinical manifestations of sickle cell disease (SCD) result from sickling of Hb S due to oxidation, which is augmented by accumulation of oxygen-free radicals. Deficiencies in normal antioxidant protective mechanism might lead to clinical manifestations of SCD like vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). The glutathione system plays an important role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to increase the severity of SCD manifestations. This report describes a case control study aimed at studying the ethnic-dependent variation in the frequency of GST gene polymorphisms among participants selected from the Egyptian population and to find out the association between GST gene polymorphisms and the severity of SCD manifestations. We measured the frequency distribution of the three GSTs gene polymorphisms in 100 Egyptian adult SCD patients and 80 corresponding controls. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay. The GSTM1 null genotype was significantly associated with ACS and VOC (P = 0.03 and 0.01, respectively). The GSTT1 null genotype was associated with significantly increased requirement of blood transfusion (P = 0.01). Absence of both GSTM1 and GSTT1 genes was significantly associated with pulmonary hypertension (P = 0.04). The non-wild-type GSTP1 polymorphism was not associated with clinical manifestations of SCD. Some GST gene polymorphisms were significantly associated with the worsening of the clinical manifestations of SCD.

When to transfuse blood in sickle cell disease? Lessons from Jehovah's Witnesses.

PubMed

Pearlman, E S; Ballas, S K

1994-01-01

Hemoglobin concentration of 7 to 8 g/dl has been considered an indication for transfusion in the general adult population and has also been frequently applied to patients with sickle cell disease (SCD). Through a review of the case histories of two patients with SCD who were also Jehovah's Witnesses and developed severe anemia, and considering as well the clinical characteristics of this population and the basic physiology of oxygen transport, the appropriateness is questioned of this transfusion "trigger" in patients with SCD. It is suggested for the latter that a Hb of 5.5 g/dl be used as an indication for transfusion except in very specific clinical circumstances.

Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

PubMed

Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

2015-10-01

Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. Copyright © 2015 Elsevier Inc. All rights reserved.

Dual kidney transplants from adult marginal donors successfully expand the limited deceased donor organ pool.

PubMed

Stratta, Robert J; Farney, Alan C; Orlando, Giuseppe; Farooq, Umar; Al-Shraideh, Yousef; Palanisamy, Amudha; Reeves-Daniel, Amber; Doares, William; Kaczmorski, Scott; Gautreaux, Michael D; Iskandar, Samy S; Hairston, Gloria; Brim, Elizabeth; Mangus, Margaret; El-Hennawy, Hany; Khan, Muhammad; Rogers, Jeffrey

2016-04-01

The need to expand the organ donor pool remains a formidable challenge in kidney transplantation (KT). The use of expanded criteria donors (ECDs) represents one approach, but kidney discard rates are high because of concerns regarding overall quality. Dual KT (DKT) may reduce organ discard and optimize the use of kidneys from marginal donors. We conducted a single-center retrospective review of outcomes in adult recipients of DKTs from adult marginal deceased donors (DD) defined by limited renal functional capacity. If the calculated creatinine clearance in an adult DD was <65 mL/min, then the kidneys were transplanted as a DKT. Over 11.5 yr, 72 DKTS were performed including 45 from ECDs, 17 from donation after cardiac death (DCD) donors, and 10 from standard criteria donors (SCD). Mean adult DD and recipient ages were both 60 yr, including 29 DDs and 26 recipients ≥65 yr of age. Mean pre-DKT waiting and dialysis vintage times were 12 months and 25 months, respectively. Actual patient and graft survival rates were 84.7% and 70.8%, respectively, with a mean follow-up of 58 months. One yr and death-censored graft survival rates were 90% and 80%, respectively. Outcomes did not differ by DD category, recipient age, or presence of delayed graft function (DGF). Eleven patients died at a mean of 32 months post-DKT (eight with functioning grafts) and 13 other patients experienced graft losses at a mean of 33 months. The incidence of DGF was 25%; there were two cases (2.8%) of primary non-function. Mean length of initial hospital stay was 7.2 d. Mean serum creatinine and glomerular filtration rate levels at 12 and 24 months were 1.5 and 53 and 1.5 mg/dL and 51 mL/min/1.73 m(2) , respectively. DKT graft survival and function were superior to concurrent single ECD and similar to concurrent SCD KTs. Two patients underwent successful kidney retransplantation, so the dialysis-free rate in surviving patients was 87%. The proportion of total renal function transplanted from

Soluble CD40L Is a Useful Marker to Predict Future Strokes in Patients With Minor Stroke and Transient Ischemic Attack.

PubMed

Li, Jiejie; Wang, Yilong; Lin, Jinxi; Wang, David; Wang, Anxin; Zhao, Xingquan; Liu, Liping; Wang, Chunxue; Wang, Yongjun

2015-07-01

Elevated soluble CD40 ligand (sCD40L) was shown to be related to cardiovascular events, but the role of sCD40L in predicting recurrent stroke remains unclear. Baseline sCD40L levels were measured in 3044 consecutive patients with acute minor stroke and transient ischemic attack, who had previously been enrolled in the Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events (CHANCE) trial. Cox proportional-hazards model was used to assess the association of sCD40L with recurrent stroke. Patients in the top tertile of sCD40L levels had increased risk of recurrent stroke comparing with those in the bottom tertile, after adjusted for conventional confounding factors (hazard ratio, 1.49; 95% confidence interval, 1.11-2.00; P=0.008). The patients with elevated levels of both sCD40L and high-sensitive C-reactive protein also had increased risk of recurrent stroke (hazard ratio, 1.81; 95% confidence interval, 1.23-2.68; P=0.003). Elevated sCD40L levels independently predict recurrent stroke in patients with minor stroke and transient ischemic attack. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00979589. © 2015 American Heart Association, Inc.

A score model to predict risk of events in patients with Brugada Syndrome.

PubMed

Sieira, Juan; Conte, Giulio; Ciconte, Giuseppe; Chierchia, Gian-Battista; Casado-Arroyo, Ruben; Baltogiannis, Giannis; Di Giovanni, Giacomo; Saitoh, Yukio; Juliá, Justo; Mugnai, Giacomo; La Meir, Mark; Wellens, Francis; Czapla, Jens; Pappaert, Gudrun; de Asmundis, Carlo; Brugada, Pedro

2017-06-07

Risk stratification in Brugada Syndrome (BS) remains challenging. Arrhythmic events can occur life-long and studies with long follow-ups are sparse. The aim of our study was to investigate long-term prognosis and risk stratification of BS patients. A single centre consecutive cohort of 400 BS patients was included and analysed. Mean age was 41.1 years, 78 patients (19.5%) had a spontaneous type I electrocardiogram (ECG). Clinical presentation was aborted sudden cardiac death (SCD) in 20 patients (5.0%), syncope in 111 (27.8%) and asymptomatic in 269 (67.3%). Familial antecedents of SCD were found in 184 individuals (46.0%), in 31 (7.8%) occurred in first-degree relatives younger than 35 years. An implantable cardioverter defibrillator (ICD) was placed in 176 (44.0%). During a mean follow-up of 80.7 months, 34 arrhythmic events occurred (event rate: 1.4% year). Variables significantly associated to events were: presentation as aborted SCD (Hazard risk [HR] 20.0), syncope (HR 3.7), spontaneous type I (HR 2.7), male gender (HR 2.7), early SCD in first-degree relatives (HR 2.9), SND (HR 5.0), inducible VA (HR 4.7) and proband status (HR 2.1). A score including ECG pattern, early familial SCD antecedents, inducible electrophysiological study, presentation as syncope or as aborted SCD and SND had a predictive performance of 0.82. A score greater than 2 conferred a 5-year event probability of 9.2%. BS patients remain at risk many years after diagnosis. Early SCD in first-degree relatives and SND are risk factors for arrhythmic events. A simple risk score might help in the stratification and management of BS patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Risk factors for sudden cardiac death among patients with schizophrenia.

PubMed

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, P<.01) and aggressive behaviors (aRR=3.99, P<.01) were associated with the risk of SCD. Regarding the latest admission, electrocardiographic abnormalities (aRR=5.46, P<.05) and administration of first-generation antipsychotics (aRR=5.13, P<.01) elevated the risk for SCD. Consistently, aggressive behaviors (aRR=3.26, P<.05) were associated with increased risk 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.

Severe Vaso-Occlusive Episodes Associated with Use of Systemic Corticosteroids in Patients with Sickle Cell Disease

PubMed Central

Darbari, Deepika S.; Castro, Oswaldo; Taylor, James G.; Fasano, Ross; Rehm, Jeffrey; Gordeuk, Victor R.; Minniti, Caterina P.

2017-01-01

Patients with sickle cell disease (SCD) are occasionally prescribed systemic corticosteroids to treat steroid-responsive conditions. Additionally, use of systemic corticosteroids for sickle cell pain episodes and acute chest syndrome is under investigation. We report 4 patients with SCD who developed severe vaso-occlusive events following the administration of systemic steroids. We also review similar cases from the literature and suggest measures for reducing the potential risk associated with use of systemic corticosteroids in this group of patients. We conclude that corticosteroids should be used with caution in patients with SCD. PMID:28643632

Subjective memory and concentration deficits in medication-free, non-elderly Asians with major depressive disorder: prevalence and their correlates.

PubMed

Srisurapanont, Manit; Bautista, Dianne; Chen, Chia-Hui; Wang, Gang; Udomratn, Pichet; Eurviriyanukul, Kanokkwan

2015-01-15

Subjective cognitive impairment (SCI) in major depressive disorder (MDD) is prevalent and correlated with disability. This study aimed to examine the prevalence rates and correlates of subjective memory deficit (SMD) and subjective concentration deficit (SCD) in medication-free, non-elderly Asians with MDD. The SMD and SCD were assessed by using two items of the Symptom Checklist-90-Revised (SCL-90-R). Other measurements of interest included the Montgomery-Asberg Depression Rating Scale (MADRS), the Fatigue Severity Scale (FSS), the Sheehan Disability Scale (SDS), and the Short Form Health Survey (SF-36). Adjusted odds ratios with 95% confidence intervals were calculated. Of 515 participants from China, Korea, Malaysia, Singapore, Taiwan, and Thailand, 347 (67.4%) and 377 (73.2%) had SMD and SCD, respectively. In total, 420 participants (81.6%) had SMD alone, SCD alone, and both deficits. Severe depression and poor mental health were significant correlates of SMD. Severe depression, clinically significant disability, poor physical health, and poor mental health were significantly independent correlates of SCD. Compared with young adults (18-34 years), older adults aged 50-65 years had a significantly lower risk of SCD (OR=.33, 95% CI: .19-.57). Only two SCL-90-R items were used to assess the SMD and SCD. The exclusion of MDD patients treated with psychotropic medications eliminated many patients commonly seen in typical clinic settings. SMD and SCD are prevalent in medication-free, non-elderly Asians with MDD. Both deficits are correlated with depression and mental health status. The independent correlation between SCD and disability underscores the crucial role of SCI in MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

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: <15 units, no 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.

Plasma Soluble CD30 as a Possible Marker of Adult T-cell Leukemia in HTLV-1 Carriers: a Nested Case-Control Study.

PubMed

Takemoto, Shigeki; Iwanaga, Masako; Sagara, Yasuko; Watanabe, Toshiki

2015-01-01

Elevated levels of soluble CD30 (sCD30) are linked with various T-cell neoplasms. However, the relationship between sCD30 levels and the development of adult T-cell leukemia (ATL) in human T-cell leukemia virus type 1 (HTLV-1) carriers remains to be clarified. We here investigated whether plasma sCD30 is associated with risk of ATL in a nested case-control study within a cohort of HTLV-1 carriers. We compared sCD30 levels between 11 cases (i.e., HTLV-1 carriers who later progressed to ATL) and 22 age-, sex- and institution-matched control HTLV-1 carriers (i.e., those with no progression). The sCD30 concentration at baseline was significantly higher in cases than in controls (median 65.8, range 27.2-134.5 U/mL vs. median 22.2, range 8.4-63.1 U/mL, P=0.001). In the univariate logistic regression analysis, a higher sCD30 (≥30.2 U/mL) was significantly associated with ATL development (odds ratio 7.88 and the 95% confidence intervals 1.35-45.8, P = 0.02). Among cases, sCD30 concentration tended to increase at the time of diagnosis of aggressive-type ATL, but the concentration was stable in those developing the smoldering-type. This suggests that sCD30 may serve as a predictive marker for the onset of aggressive-type ATL in HTLV-1 carriers.

Very high levels of soluble CD30 recognize the patients with classical Hodgkin's lymphoma retaining a very poor prognosis.

PubMed

Visco, Carlo; Nadali, Gianpaolo; Vassilakopoulos, Theodoros P; Bonfante, Valeria; Viviani, Simonetta; Gianni, Alessandro M; Federico, Massimo; Luminari, Stefano; Peethambaram, Prema; Witzig, Thomas E; Pangalis, Gerassimos; Cabanillas, Fernando; Medeiros, L Jeffrey; Sarris, Andreas H; Pizzolo, Giovanni

2006-11-01

To evaluate the prognostic role of pretreatment serum levels of soluble CD30 (sCD30) in patients with advanced stage classical Hodgkin's lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine or equivalent regimens. We identified 321 previously untreated patients with cHL who presented to the participating centers between 1985 and 2002, and had serum samples available for the determination of sCD30 levels. With a median follow-up of 72 months, the actuarial 5-year overall survival was 82%, and failure-free survival (FFS) was 71%. The median serum level of sCD30 was 65 U/mL (range: 1-2230), and was significantly higher (P < 0.0001) when compared with a group of 113 healthy controls (4 U/mL, range: 0-20). Increasing level of sCD30 was associated with a continuous worsening of FFS and OS, and patients with sCD30 >or=200 U/mL had a 5-year FFS of 39%. With multivariate analysis, sCD30, Ann Arbor stage, and lactic acid dehydrogenase were significant independent factors in terms of FFS. The association of the above-mentioned three independent prognostic variables could discriminate 22% of patients with 5-year FFS of 40%. Our data confirm the independent prognostic role of sCD30 in identifying the patients with high risk of treatment failure, and show that its association with other variables can recognize patients with FFS considerably lower than 50%.

Cost-effectiveness of In-home Automated External Defibrillators for Individuals at Increased Risk of Sudden Cardiac Death

PubMed Central

Cram, Peter; Vijan, Sandeep; Katz, David; Fendrick, A Mark

2005-01-01

BACKGROUND/OBJECTIVE In-home automated external defibrillators (AEDs) are increasingly recommended as a means for improving survival of cardiac arrests that occur at home. The current study was conducted to explore the relationship between individuals' risk of cardiac arrest and cost-effectiveness of in-home AED deployment. DESIGN Markov decision model employing a societal perspective. PATIENTS Four hypothetical cohorts of American adults 60 years of age at progressively greater risk for sudden cardiac death (SCD): 1) all adults (annual probability of SCD 0.4%); 2) adults with multiple SCD risk factors (probability 2%); 3) adults with previous myocardial infarction (probability 4%); and 4) adults with ischemic cardiomyopathy unable to receive an implantable defibrillator (probability 6%). INTERVENTION Strategy 1: individuals suffering an in-home cardiac arrest were treated with emergency medical services equipped with AEDs (EMS-D). Strategy 2: individuals suffering an in-home cardiac arrest received initial treatment with an in-home AED, followed by EMS. RESULTS Assuming cardiac arrest survival rates of 15% with EMS-D and 30% with AEDs, the cost per quality-adjusted life-year gained (QALY) of providing in-home AEDs to all adults 60 years of age is $216,000. Costs of providing in-home AEDs to adults with multiple risk factors (2% probability of SCD), previous myocardial infarction (4% probability), and ischemic cardiomyopathy (6% probability) are $132,000, $104,000, and $88,000, respectively. CONCLUSIONS The cost-effectiveness of in-home AEDs is intimately linked to individuals' risk of SCD. However, providing in-home AEDs to all adults over age 60 appears relatively expensive. PMID:15836529

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

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

PubMed

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 < .001). Patients with 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 < .001). Patients with CSF and SCD also demonstrated significantly lower pneumatization rates, as low as 17% to 23% overlaying the PG and IAC ( P < .001). There were no statistically significant correlations found between age, sex, BMI, and LSB height/thickness at any measurement location in any group. Conclusions Patients with 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.

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

PubMed

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 < 0.001) and hepatic steatosis (B 23.04, P < 0.001) were independently associated with CAP by multivariate analysis. The AUROCs were slightly higher for SCD <25 mm compared to those for SCD ≥25 mm for steatosis ≥5% (0.88 vs. 0.81), >33% (0.90 vs. 0.85) and >66% (0.84 vs. 0.72). For SCD <25 mm, the optimal CAP cut-offs for differentiating steatosis ≥5%, >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.

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

PubMed

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.

Soluble CD163 is an indicator of liver inflammation and fibrosis in patients chronically infected with the hepatitis B virus.

PubMed

Dultz, G; Gerber, L; Farnik, H; Berger, A; Vermehren, J; Pleli, T; Zeuzem, S; Piiper, A; Kronenberger, B; Waidmann, O

2015-04-01

Soluble CD163 (sCD163), a marker for macrophage activation, was found to be associated with the severity of liver cirrhosis. The aim of the current study was to investigate whether serum sCD163 levels correlate with liver inflammation and fibrosis in patients with chronic hepatitis B virus (HBV) infection. In a retrospective cohort study, serum sCD163 levels were assessed by ELISA together with clinical and laboratory data in 186 patients with chronic HBV infection and 15 healthy controls. The relation between parameters for liver fibrosis and necroinflammation and sCD163 levels was analysed. Additionally, sCD163 was quantified in a subset of follow-up serum samples after initiation of antiviral treatment. sCD163 levels differed among phases of chronic HBV infection (P < 0.0001), and sCD163 concentrations were associated with inflammatory activity and fibrosis in the liver. sCD163 levels ≥ 1961 ng/l had a high specificity in the identification of subjects with substantial fibrosis (F ≥ 2). sCD163 concentrations decreased significantly after initiation of antiviral treatment. The correlation of sCD163 levels with necroinflammation and fibrosis and the sCD163 decline under treatment indicates that macrophage activation plays a role in HBV-related liver pathogenesis. © 2014 John Wiley & Sons Ltd.

Improving Sickle Cell Transitions of Care Through Health Information Technology.

PubMed

Frost, Jennifer R; Cherry, Rebecca K; Oyeku, Suzette O; Faro, Elissa Z; Crosby, Lori E; Britto, Maria; Tuchman, Lisa K; Horn, Ivor B; Homer, Charles J; Jain, Anjali

2016-07-01

Transitions between inpatient and outpatient care and pediatric to adult care are associated with increased mortality for sickle cell disease (SCD) patients. As accurate and timely sharing of health information is essential during transitions, a health information technology (HIT)-enabled tool holds promise to improve care transitions. From 2012 through 2014, the team conducted and analyzed data from an environmental scan, key informant interviews, and focus groups to inform the development of an HIT-enabled tool for SCD patients' use during care transitions. The scan included searches of peer-reviewed and gray literature to understand SCD patient needs, transition concerns, and best practices in mobile health applications, and searches of websites and online stores to identify existing transition tools and their features. Eleven focus groups consisted of four groups of SCD patients of varying ages (≥9 years); three groups of parents/caregivers of SCD patients; three groups of providers; and one with IT developers. In focus groups, patients and caregivers reported that the transition from home to the emergency department (ED) was the most challenging; the ED was also where transitions from pediatric to adult care usually occurred. Patients felt they were not taken seriously by unfamiliar ED providers, and their inability to convey their diagnosis, pain regimen, and detailed medical history while in significant pain hindered care. The environmental scan did not reveal an existing suitable transition tool, but patients, parents, providers, and IT experts saw the potential and appeal of creating a tool to meet ED health information needs to improve care transitions. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

Pattern of Serum Cytokine Expression and T-Cell Subsets in Sickle Cell Disease Patients in Vaso-Occlusive Crisis▿

PubMed Central

Musa, Bolanle O. P.; Onyemelukwe, Geoffrey C.; Hambolu, Joseph O.; Mamman, Aisha I.; Isa, Albarka H.

2010-01-01

The pathogenesis of sickle vaso-occlusive crisis (VOC) in sickle cell disease (SCD) patients involves the accumulation of rigid sickle cells and the stimulation of an ongoing inflammatory response, as well as the stress of infections. The immune response, via cytokine imbalances and deregulated T-cell subsets, also has been proposed to contribute to the development of VOC. In this study, a panel of high-sensitivity cytokine kits was used to investigate cytokines in the sera of SCD patients in VOC. The results were compared primarily with those for stable SCD patients and secondarily with those for normal healthy people who served as controls. The cytokines studied included interleukin-2 (IL-2), IL-4, and IL-10. Lymphocyte subsets of patients with VOC were also studied and were compared with those of both control groups (20 stable patients without crisis [SCD group] and 20 normal healthy controls [NHC]). The VOC group was notable for remarkably elevated levels of IL-4, among the three cytokines tested, compared with those for the SCD and NHC groups. Patients with VOC also differed from stable SCD patients and NHC by having notably lower IL-10 levels, as well as the lowest ratio of CD4+ to CD8+ T cells (0.7). The patterns of the proinflammatory cytokine IL-2 did not differ between VOC and stable SCD patients, but NHC had significantly lower IL-2 levels than both the VOC and SCD groups. Our results demonstrate coexisting levels, both high and low, of TH1- and TH2-type cytokines, as well as diminished levels of T-cell subsets in VOC. These results are discussed in an effort to better understand the importance of the immune system profile in the pathogenesis of sickle cell VOC. Since the possibility that a cytokine imbalance is implicated in the pathogenesis of sickle cell crisis has been raised, our results should prompt further investigation of the host immune response in terms of TH1 and TH2 balance in sickle cell crisis. PMID:20130127

Elevated levels of soluble CD14 in serum of patients with acute Plasmodium falciparum malaria

PubMed Central

WENISCH, C; WENISCH, H; PARSCHALK, B; VANIJANONTA, S; BURGMANN, H; EXNER, M; ZEDWITZ-LIEBENSTEIN, K; THALHAMMER, F; GEORGOPOULOS, A; GRANINGER, W; LOOAREESUWAN, S

1996-01-01

Serum sCD14, tumour necrosis factor-alpha (TNF-α), IL-6, and endotoxin were analysed in 45 patients with complicated malaria, in 14 patients with Gram-negative septicaemia and in 24 healthy subjects by ELISA. Malaria patients with renal failure (n = 16) had higher levels than patients without renal failure (n = 29) (8116+1440 μg/lversus 9453+1017 μg/lP<0.05) and both had higher levels than patients with septicaemia (6155+1635μg/l) and normal subjects (2776+747 μg/l). A significant correlation between sCD14 and IL-6 (r = 0.756) and TNF (r = 0.822) existed. However, no relation between sCD14 and serum endotoxin or indices of clinical disease severity (parasitaemia, fever, parasite or fever clearance time) was seen. Although the role of sCD14 in malaria remains to be determined, elevated levels may participate in the inflammatory response in complicated malaria. PMID:8697639

The evaluation of a new apheresis device for automated red blood cell exchange procedures in patients with sickle cell disease.

PubMed

Quirolo, Keith; Bertolone, Salvatore; Hassell, Kathryn; Howard, Thomas; King, Karen E; Rhodes, Diane K; Bill, Jerry

2015-04-01

The Spectra Optia apheresis system (SO), a blood component separator, can be used to perform red blood cell exchange (RBCX) procedures for the transfusion management of sickle cell disease (SCD) in adults and children. This study was designed to evaluate the performance of the SO RBCX protocols (exchange and depletion/exchange) in patients with SCD. Patients with SCD and a need for an RBCX procedure as part of a chronic program or as a single procedure were enrolled in this multicenter, single-arm, open-label study. The primary goal of the study was to confirm that the predicted percentage of the patient's original RBCs remaining at the end of the procedure (FCRp) reflects the actual cell fraction remaining, as measured by %HbS (FCRa). Secondary endpoints included ability of the SO to achieve the desired final hematocrit (Hct) and device-related serious adverse events (SAEs). Seventy-two patients 12 years of age or older were enrolled in the study; 60 were evaluable. The ratio of FCRa to FCRp after the RBCX procedure was 0.90, well within the prespecified range of 0.75 to 1.25. The SO was able to achieve the desired final Hct in the evaluable population. The safety profile was favorable, and no patients had an SAE or unexpected adverse device effect or withdrew from the procedure or treatment due to an adverse event. The SO performed effectively and safely for both the RBCX procedure and the RBCX depletion/exchange procedure. © 2014 AABB.

Oral health management considerations for patients with sickle cell disease.

PubMed

Kawar, Nadia; Alrayyes, Sahar; Yang, Bin; Aljewari, Haider

2018-06-01

Sickle cell disease (SCD) can affect many systems in the body including the oral cavity. This necessitates modifications in oral health care management of these patients. The purpose of this paper is to make recommendations for management of SCD patients according to their oral health care needs based on the known findings. Copyright © 2018 Mosby, Inc. All rights reserved.

T-Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure.

PubMed

Ramírez, Julia; Orini, Michele; Mincholé, Ana; Monasterio, Violeta; Cygankiewicz, Iwona; Bayés de Luna, Antonio; Martínez, Juan Pablo; Pueyo, Esther; Laguna, Pablo

2017-05-19

Patients with chronic heart failure are at high risk of sudden cardiac death (SCD). Increased dispersion of repolarization restitution has been associated with SCD, and we hypothesize that this should be reflected in the morphology of the T-wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (ECG)-based index characterizing T-wave morphology restitution (TMR), and to assess its association with SCD risk in a population of chronic heart failure patients. Holter ECGs from 651 ambulatory patients with chronic heart failure from the MUSIC (MUerte Súbita en Insuficiencia Cardiaca) study were available for the analysis. TMR was quantified by measuring the morphological variation of the T-wave per RR increment using time-warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other ECG-derived indices, such as T-wave alternans and heart rate variability. TMR was significantly higher in SCD victims than in the rest of patients (median 0.046 versus 0.039, P <0.001). When TMR was dichotomized at TMR=0.040, the SCD rate was significantly higher in the TMR≥0.040 group ( P <0.001). Cox analysis revealed that TMR≥0.040 was strongly associated with SCD, with a hazard ratio of 3.27 ( P <0.001), independently of clinical and ECG-derived variables. No association was found between TMR and pump failure death. This study shows that TMR is specifically associated with SCD in a population of chronic heart failure patients, and it is a better predictor than clinical and ECG-derived variables. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

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

PubMed Central

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

Headache and Facial Pain in Sickle Cell Disease.

PubMed

Vgontzas, Angeliki; Charleston, Larry; Robbins, Matthew S

2016-03-01

Children and adolescents with sickle cell disease (SCD) have a high prevalence of recurrent headaches (24.0-43.9 %). Acute presentation with headache can be diagnostically challenging, as the clinician must consider evaluation of several potentially devastating conditions including vascular diseases (stroke, hemorrhage, venous sinus thrombosis, moyamoya, posterior reversible encephalopathy syndrome), facial and orbital bone infarcts, dental pain, and osteomyelitis. Patients with SCD and primary headache disorders may benefit from comprehensive headache treatment plans that include abortive therapy, prophylactic therapy, and non-pharmacological modalities. Although there is limited data in adults, those with SCD are at risk for medication overuse headache secondary to frequent opioid use. Addressing headache in patients with SCD may help to reduce their use of opioids and disability and improve pain and quality of life.

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

PubMed

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.

Cognitive deficits are associated with unemployment in adults with sickle cell anemia.

PubMed

Sanger, Maureen; Jordan, Lori; Pruthi, Sumit; Day, Matthew; Covert, Brittany; Merriweather, Brenda; Rodeghier, Mark; DeBaun, Michael; Kassim, Adetola

2016-08-01

An estimated 25-60% of adults with sickle cell disease (SCD) are unemployed. Factors contributing to the high unemployment rate in this population are not well studied. With the known risk of cognitive deficits associated with SCD, we tested the hypothesis that unemployment is related to decrements in intellectual functioning. We conducted a retrospective chart review of 50 adults with sickle cell anemia who completed cognitive testing, including the Wechsler Adult Intelligence Scale-IV, as part of standard care. Employment status was recorded at the time of testing. Medical variables examined as possible risk factors for unemployment included disease phenotype, cerebral infarction, and pain frequency. The mean age of the sample was 30.7 years (range = 19-59); 56% were women. Almost half of the cohort (44%) were unemployed. In a multivariate logistic regression model, lower IQ scores (odds ratio = 0.88; p = .002, 95% confidence interval, CI [0.82, 0.96]) and lower educational attainment (odds ratio = 0.13; p = .012, 95% CI [0.03, 0.65]) were associated with increasing odds of unemployment. The results suggest that cognitive impairment in adults with sickle cell anemia may contribute to the risk of unemployment. Helping these individuals access vocational rehabilitation services may be an important component of multidisciplinary care.

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

Effects of Meditation versus Music Listening on Perceived Stress, Mood, Sleep, and Quality of Life in Adults with Early Memory Loss: A Pilot Randomized Controlled Trial.

PubMed

Innes, Kim E; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti

2016-04-08

Older adults with subjective cognitive decline (SCD) are at increased risk not only for Alzheimer's disease, but for poor mental health, impaired sleep, and diminished quality of life (QOL), which in turn, contribute to further cognitive decline, highlighting the need for early intervention. In this randomized controlled trial, we assessed the effects of two 12-week relaxation programs, Kirtan Kriya Meditation (KK) and music listening (ML), on perceived stress, sleep, mood, and health-related QOL in older adults with SCD. Sixty community-dwelling older adults with SCD were randomized to a KK or ML program and asked to practice 12 minutes daily for 12 weeks, then at their discretion for the following 3 months. At baseline, 12 weeks, and 26 weeks, perceived stress, mood, psychological well-being, sleep quality, and health-related QOL were measured using well-validated instruments. Fifty-three participants (88%) completed the 6-month study. Participants in both groups showed significant improvement at 12 weeks in psychological well-being and in multiple domains of mood and sleep quality (p's≤0.05). Relative to ML, those assigned to KK showed greater gains in perceived stress, mood, psychological well-being, and QOL-Mental Health (p's≤0.09). Observed gains were sustained or improved at 6 months, with both groups showing marked and significant improvement in all outcomes. Changes were unrelated to treatment expectancies. Findings suggest that practice of a simple meditation or ML program may improve stress, mood, well-being, sleep, and QOL in adults with SCD, with benefits sustained at 6 months and gains that were particularly pronounced in the KK group.

Effects of Meditation versus Music Listening on Perceived Stress, Mood, Sleep, and Quality of Life in Adults with Early Memory Loss: A Pilot Randomized Controlled Trial

PubMed Central

Innes, Kim E.; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti

2017-01-01

Background Older adults with subjective cognitive decline (SCD) are at increased risk not only for Alzheimer’s disease, but for poor mental health, impaired sleep, and diminished quality of life (QOL), which in turn, contribute to further cognitive decline, highlighting the need for early intervention. Objective In this randomized controlled trial, we assessed the effects of two 12-week relaxation programs, Kirtan Kriya Meditation (KK) and music listening (ML), on perceived stress, sleep, mood, and health-related QOL in older adults with SCD. Methods Sixty community-dwelling older adults with SCD were randomized to a KK or ML program and asked to practice 12 minutes daily for 12 weeks, then at their discretion for the following 3 months. At baseline, 12 weeks, and 26 weeks, perceived stress, mood, psychological well-being, sleep quality, and health-related QOL were measured using well-validated instruments. Results Fifty-three participants (88%) completed the 6-month study. Participants in both groups showed significant improvement at 12 weeks in psychological well-being and in multiple domains of mood and sleep quality (p’s ≤ 0.05). Relative to ML, those assigned to KK showed greater gains in perceived stress, mood, psychological well-being, and QOL-Mental Health (p’s ≤ 0.09). Observed gains were sustained or improved at 6 months, with both groups showing marked and significant improvement in all outcomes. Changes were unrelated to treatment expectancies. Conclusions Findings suggest that practice of a simple meditation or ML program may improve stress, mood, well-being, sleep, and QOL in adults with SCD, with benefits sustained at 6 months and gains that were particularly pronounced in the KK group. PMID:27079708

Prasugrel hydrochloride for the treatment of sickle cell disease.

PubMed

Conran, Nicola; Rees, David C

2017-07-01

Therapeutic options for sickle cell disease (SCD) are limited and, currently, only one drug (hydroxyurea) has FDA approval for the treatment of adult SCD. While this genetic disease is caused by hemoglobin polymerization, subsequent downstream events trigger platelet activation, vaso-occlusion and the disease's complex pathophysiology. Areas covered: The oral thienopyridine, prasugrel hydrochloride, irreversibly inhibits the P2Y12 receptors, inhibiting ADP-dependent platelet activation. We discuss recent clinical trials evaluating the pharmokinetics of prasugrel and its potential for use in SCD. Expert opinion: Prasugrel administration in SCD appears to be well tolerated and safe. However, although this drug modestly inhibits platelet activity in these patients, administration of prasugrel to a large group of children and adolescents for up to 24 months failed to convincingly reduce vaso-occlusive complications. Speculatively, prasugrel may be of occasional use for off-license purposes in patients unable or unwilling to take hydroxyurea (particularly in 12-17-year olds). Although there is currently no prospect of prasugrel being licensed for use in SCD, the success of on-going trials of other antiplatelet agents in SCD might lead to further trials of prasugrel in SCD.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

Subjective Cognitive Decline in Older Adults: An Overview of Self-Report Measures Used Across 19 International Research Studies

PubMed Central

Rabin, Laura A.; Smart, Colette M.; Crane, Paul K.; Amariglio, Rebecca E.; Berman, Lorin M.; Boada, Mercè; Buckley, Rachel F.; Chételat, Gaël; Dubois, Bruno; Ellis, Kathryn A.; Gifford, Katherine A.; Jefferson, Angela L.; Jessen, Frank; Katz, Mindy J.; Lipton, Richard B.; Luck, Tobias; Maruff, Paul; Mielke, Michelle M.; Molinuevo, José Luis; Naeem, Farnia; Perrotin, Audrey; Petersen, Ronald C.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Riedel-Heller, Steffi G.; Risacher, Shannon L.; Rodriguez, Octavio; Sachdev, Perminder S.; Saykin, Andrew J.; Slavin, Melissa J.; Snitz, Beth E.; Sperling, Reisa A.; Tandetnik, Caroline; van der Flier, Wiesje M.; Wagner, Michael; Wolfsgruber, Steffen; Sikkes, Sietske A.M.

2015-01-01

Research increasingly suggests that subjective cognitive decline (SCD) in older adults, in the absence of objective cognitive dysfunction or depression, may be a harbinger of non-normative cognitive decline and eventual progression to dementia. Little is known, however, about the key features of self-report measures currently used to assess SCD. The Subjective Cognitive Decline Initiative (SCD-I) Working Group is an international consortium established to develop a conceptual framework and research criteria for SCD (Jessen et al., 2014, Alzheimers Dement 10, 844–852). In the current study we systematically compared cognitive self-report items used by 19 SCD-I Working Group studies, representing 8 countries and 5 languages. We identified 34 self-report measures comprising 640 cognitive self-report items. There was little overlap among measures—approximately 75% of measures were used by only one study. Wide variation existed in response options and item content. Items pertaining to the memory domain predominated, accounting for about 60% of items surveyed, followed by executive function and attention, with 16% and 11% of the items, respectively. Items relating to memory for the names of people and the placement of common objects were represented on the greatest percentage of measures (56% each). Working group members reported that instrument selection decisions were often based on practical considerations beyond the study of SCD specifically, such as availability and brevity of measures. Results document the heterogeneity of approaches across studies to the emerging construct of SCD. We offer preliminary recommendations for instrument selection and future research directions including identifying items and measure formats associated with important clinical outcomes. PMID:26402085

A telephonic mindfulness-based intervention for persons with sickle cell disease: study protocol for a randomized controlled trial.

PubMed

Williams, Hants; Silva, Susan; Simmons, Leigh Ann; Tanabe, Paula

2017-05-15

One of the most difficult symptoms for persons with sickle cell disease (SCD) to manage is chronic pain. Chronic pain impacts approximately one-third of persons with SCD and is associated with increased pain intensity, pain behavior, and frequency and duration of hospital visits. A promising category of nonpharmacological interventions for managing both physical and affective components of pain are mindfulness-based interventions (MBIs). The primary aim of this study is to conduct a randomized controlled study to evaluate the acceptability and feasibility, as well as to determine the preliminary efficacy, of a telephonic MBI for adults with SCD who have chronic pain. We will enroll 60 adult patients with SCD and chronic pain at an outpatient comprehensive SCD center in the southeastern United States. Patients will be randomized to either an MBI or a wait-listed control group. The MBI group will complete a six-session (60 minutes), telephonically delivered, group-based MBI program. The feasibility, acceptability, and efficacy of the MBI regarding pain catastrophizing will be assessed by administering questionnaires at baseline and weeks 1, 3, and 6. In addition, ten randomly selected MBI participants will complete semistructured interviews to help determine intervention acceptability. In this study protocol, we report detailed methods of the randomized controlled trial. Findings of this study will be useful to determine the acceptability, feasibility, and efficacy of an MBI for persons with SCD and chronic pain. ClinicalTrials.gov identifier: NCT02394587 . Registered on 9 February 2015.

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

PubMed Central

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

High bone mineral density in sickle cell disease: Prevalence and characteristics.

PubMed

De Luna, Gonzalo; Ranque, Brigitte; Courbebaisse, Marie; Ribeil, Jean-Antoine; Khimoud, Djamal; Dupeux, Sidonie; Silvera, Jonathan; Offredo, Lucile; Pouchot, Jacques; Arlet, Jean-Benoît

2018-05-01

Osteosclerosis (OSC) is a rarely studied complication of sickle cell disease (SCD). The objective of our study was to determine the prevalence and characteristics of high bone mineral density (BMD) and its radiological features in adult SCD patients. This prospective observational study was conducted from May 2007 to May 2016 in consecutive patients with steady-state SCD at two university hospitals. The BMD of the lumbar spine (L1-L4) and right femoral neck was determined by dual energy X-ray absorptiometry. Clinical, laboratory and radiographic data were recorded. High BMD was defined as a BMD Z-score of at least +2.5 standard deviations at the lumbar spine or hip. The characteristics of the patients with high BMD were compared to those of individuals with low or middle BMD, using multivariate ordinal logistic regression. 135 patients (86 women and 49 men) with a median age of 27 (IQR 23-33) years were included. High BMD was diagnosed in 20 (15%) patients with a median age of 33.5 (IQR 28-45) years. The SCD genotypes of these patients were SS in 11, SC in 5, S/beta+ in 3, and S/beta0 in 1. High BMD patients more frequently harbored the S/beta SCD genotype (21% vs 5% in non-high BMD patients; p=0.047) and were older (p=0.0007). Compared to patients with low or middle BMD, after adjustment for age and SCD genotype, high BMD patients had a higher prevalence of avascular necrosis history (p=0.009), higher BMI (p=0.007), and lower serum resorption marker CTX (p=0.04), bilirubin (p=0.02) and parathyroid hormone levels (p=0.02). There were no differences between groups regarding fracture history, H-shaped vertebrae or other biological variables. High-BMD values is a common manifestation in SCD patients, especially in those with the S/beta-thalassemia genotypes. The prevalence of high-BMD in SCD is associated with older age, suggesting that it will be more common in the future because the life span of patients with SCD is increasing thanks to significant progress in SCD

TH1/TH2 cytokines and soluble CD30 levels in kidney allograft patients with donor bone marrow cell infusion.

PubMed

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 < .0001, respectively). Higher levels of 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.

NT-pro Brain Natriuretic Peptide Levels and the Risk of Death in the Cooperative Study of Sickle Cell Disease

PubMed Central

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

2011-01-01

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 ≥160 ng/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 ≥160 ng/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. PMID:21689089

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

PubMed

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.

Platelet Activation in Patients with Atherosclerotic Renal Artery Stenosis Undergoing Stent Revascularization

PubMed Central

Adlakha, Satjit; Reed, Grant; Brewster, Pamela; Kennedy, David; Burket, Mark W.; Colyer, William; Yu, Haifeng; Zhang, Dong; Shapiro, Joseph I.; Cooper, Christopher J.

2011-01-01

Summary Background and objectives Soluble CD40 ligand (sCD40L) is a marker of platelet activation; whether platelet activation occurs in the setting of renal artery stenosis and stenting is unknown. Additionally, the effect of embolic protection devices and glycoprotein IIb/IIIa inhibitors on platelet activation during renal artery intervention is unknown. Design, setting, participants, & measurements Plasma levels of sCD40L were measured in healthy controls, patients with atherosclerosis without renal stenosis, and patients with renal artery stenosis before, immediately after, and 24 hours after renal artery stenting. Results Soluble CD40L levels were higher in renal artery stenosis patients than normal controls (347.5 ± 27.0 versus 65.2 ± 1.4 pg/ml, P < 0.001), but were similar to patients with atherosclerosis without renal artery stenosis. Platelet-rich emboli were captured in 26% (9 of 35) of embolic protection device patients, and in these patients sCD40L was elevated before the procedure. Embolic protection device use was associated with a nonsignificant increase in sCD40L, whereas sCD40L declined with abciximab after the procedure (324.9 ± 42.5 versus 188.7 ± 31.0 pg/ml, P = 0.003) and at 24 hours. Conclusions Atherosclerotic renal artery stenosis is associated with platelet activation, but this appears to be related to atherosclerosis, not renal artery stenosis specifically. Embolization of platelet-rich thrombi is common in renal artery stenting and is inhibited with abciximab. PMID:21817131

Impact of a Clinical Pharmacy Service on the Management of Patients in a Sickle Cell Disease Outpatient Center.

PubMed

Han, Jin; Bhat, Shubha; Gowhari, Michel; Gordeuk, Victor R; Saraf, Santosh L

2016-11-01

Ambulatory care clinical pharmacy services have expanded beyond primary care settings, but literature supporting the benefits of clinical pharmacy involvement with patients who have rare diseases such as sickle cell disease (SCD) is lacking. Hydroxyurea is the only agent approved by the U.S. Food and Drug Administration for the treatment of SCD; full benefit in controlling pain episodes and other complications is achieved through monitored escalation to a maximum tolerated dose. The primary objective of this analysis was to evaluate the impact of a newly implemented clinical pharmacy service on the management of patients with SCD. We performed a retrospective cross-sectional analysis of 385 adults with SCD who received care between January 1, 2014, and December 31, 2014, at a single Sickle Cell Outpatient Center that implemented a clinical pharmacy service in August 2013. Data were collected on hydroxyurea dose escalation, immunization completion rates, and health maintenance metrics (screening for nephropathy with microalbuminuria testing, retinopathy with annual retinal examinations, and pulmonary hypertension with echocardiography). The impact of the clinical pharmacy service on quality measurements was evaluated by using univariate and multivariate analyses. The number of pharmacist encounters, defined as a clinic visit when a clinical pharmacist interacted with a patient as documented in the medical records, was associated with an improved hydroxyurea dose escalation rate (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.07-2.05, p=0.02). Immunization rates for the 23-valent pneumococcal polysaccharide vaccine, the 13-valent pneumococcal conjugate vaccine, and influenza vaccine were 66%, 47%, and 62%, respectively. The number of pharmacist encounters was associated with improved immunization completion rates (OR 1.38, 95% CI 1.17-1.62, p<0.001). Improved screening for microalbuminuria (OR 2.14, 95% CI 1.60-2.86, p<0.001) and sickle cell retinopathy (OR 1

Reactivity to Daily Stressors in Adulthood: The Importance of Stressor Type in Characterizing Risk Factors

PubMed Central

Hay, Elizabeth L.; Diehl, Manfred

2010-01-01

This study examined daily stressors in adults aged 18 to 89 years (M = 49.6 years) over 30 days. We examined the role of individual factors (i.e., age, self-concept differentiation, perceived control) in physical and psychological reactivity to interpersonal, network, home, and health stressors. Findings were consistent with the perspective that adults were less reactive to stress on days they felt in control and that younger adults and adults with high self-concept differentiation (SCD) were more vulnerable to stress. Age, SCD, and daily perceived control, however, interacted with one another and findings varied by stressor type. For example, age differences in reactivity were moderated by SCD whereby older adults with low SCD were particularly resilient to home stressors. Also, whether perceived control buffered adults' reactivity to daily stress varied by age and SCD. For example, only adults with high SCD were psychologically reactive to network stressors and only on days they reported having low control. The findings emphasize the importance of considering how individual characteristics interact in varying ways to influence stress reactivity to different types of stressors. PMID:20230133

Assessing cardiac and liver iron overload in chronically transfused patients with sickle cell disease.

PubMed

Badawy, Sherif M; Liem, Robert I; Rigsby, Cynthia K; Labotka, Richard J; DeFreitas, R Andrew; Thompson, Alexis A

2016-11-01

Transfusional iron overload represents a substantial challenge in the management of patients with sickle cell disease (SCD) who receive chronic or episodic red blood cell transfusions. Iron-induced cardiomyopathy is a leading cause of death in other chronically transfused populations but rarely seen in SCD. Study objectives were to: (i) examine the extent of myocardial and hepatic siderosis using magnetic resonance imaging (MRI) in chronically transfused SCD patients, and (ii) evaluate the relationship between long-term (over the 5 years prior to enrolment) mean serum ferritin (MSF), spot-ferritin values and liver iron content (LIC) measured using MRI and liver biopsy. Thirty-two SCD patients (median age 15 years) with transfusional iron overload were recruited from two U.S. institutions. Long-term MSF and spot-ferritin values significantly correlated with LIC by MRI-R2* (r = 0·77, P < 0·001; r = 0·82, P < 0·001, respectively). LIC by MRI-R2* had strong positive correlation with LIC by liver biopsy (r = 0·98, P < 0·001) but modest inverse correlation with cardiac MRI-T2* (r = -0·41, P = 0·02). Moderate to severe transfusional iron overload in SCD was not associated with aberrations in other measures of cardiac function based on echocardiogram or serum biomarkers. Our results suggest that SCD patients receiving chronic transfusions may not demonstrate significant cardiac iron loading irrespective of ferritin trends, LIC and erythropoiesis suppression. © 2016 John Wiley & Sons Ltd.

T-Cell Surface Antigens and sCD30 as Biomarkers of the Risk of Rejection in Solid Organ Transplantation.

PubMed

Wieland, Eberhard; Shipkova, Maria

2016-04-01

T-cell activation is a characteristic of organ rejection. T cells, located in the draining lymph nodes of the transplant recipient, are faced with non-self-molecules presented by antigen presenting cells and become activated. Activated T cells are characterized by up-regulated surface antigens, such as costimulatory molecules, adhesion molecules, chemokine receptors, and major histocompatibility complex class II molecules. Surface antigen expression can be followed by flow cytometry using monoclonal antibodies in either cell function assays using donor-specific or nonspecific stimulation of isolated cells or whole blood and without stimulation on circulating lymphocytes. Molecules such as CD30 can be proteolytically cleaved off the surface of activated cells in vivo, and the determination of the soluble protein (sCD30) in serum or plasma is performed by immunoassays. As promising biomarkers for rejection and long-term transplant outcome, CD28 (costimulatory receptor for CD80 and CD86), CD154 (CD40 ligand), and sCD30 (tumor necrosis factor receptor superfamily, member 8) have been identified. Whereas cell function assays are time-consuming laboratory-developed tests which are difficult to standardize, commercial assays are frequently available for soluble proteins. Therefore, more data from clinical trials have been published for sCD30 compared with the surface antigens on activated T cells. This short review summarizes the association between selected surface antigens and immunosuppression, and rejection in solid organ transplantation.

AFM force measurements of the gp120-sCD4 and gp120 or CD4 antigen-antibody interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yong, E-mail: dr_yongchen@hotmail.com; Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL 60612; Zeng, Gucheng

2011-04-08

Highlights: {yields} The unbinding force of sCD4-gp120 interaction was 25.45 {+-} 20.46 pN. {yields} The unbinding force of CD4 antigen-antibody interaction was 51.22 {+-} 34.64 pN. {yields} The unbinding force of gp120 antigen-antibody interaction was 89.87 {+-} 44.63 pN. {yields} The interaction forces between various HIV inhibitors and the target molecules are significantly different. {yields} Functionalizing on AFM tip or substrate of an interaction pair caused different results. -- Abstract: Soluble CD4 (sCD4), anti-CD4 antibody, and anti-gp120 antibody have long been regarded as entry inhibitors in human immunodeficiency virus (HIV) therapy. However, the interactions between these HIV entry inhibitors andmore » corresponding target molecules are still poorly understood. In this study, atomic force microscopy (AFM) was utilized to investigate the interaction forces among them. We found that the unbinding forces of sCD4-gp120 interaction, CD4 antigen-antibody interaction, and gp120 antigen-antibody interaction were 25.45 {+-} 20.46, 51.22 {+-} 34.64, and 89.87 {+-} 44.63 pN, respectively, which may provide important mechanical information for understanding the effects of viral entry inhibitors on HIV infection. Moreover, we found that the functionalization of an interaction pair on AFM tip or substrate significantly influenced the results, implying that we must perform AFM force measurement and analyze the data with more caution.« less

Differences in Pain Management Between Hematologists and Hospitalists Caring for Patients with Sickle Cell Disease Hospitalized for Vaso-Occlusive Crisis

PubMed Central

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

2013-01-01

Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by 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). In conclusion, 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. PMID:23669451

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

PubMed

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.

The Acute Risks of Exercise in Apparently Healthy Adults and Relevance for Prevention of Cardiovascular Events.

PubMed

Goodman, Jack M; Burr, Jamie F; Banks, Laura; Thomas, Scott G

2016-04-01

Increased physical activity (PA) is associated with improved quality of life and reductions in cardiovascular (CV) morbidity and all-cause mortality in the general population in a dose-response manner. However, PA acutely increases the risk of adverse CV event or sudden cardiac death (SCD) above levels expected at rest. We review the likelihood of adverse CV events related to exercise in apparently healthy adults and strategies for prevention, and contextualize our understanding of the long-term risk reduction conferred from PA. A systematic review of the literature was performed using electronic databases; additional hand-picked relevant articles from reference lists and additional sources were included after the search. The incidence of adverse CV events in adults is extremely low during and immediately after PA of varying types and intensities and is significantly lower in those with long-standing PA experience. The risk of SCD and nonfatal events during and immediately after PA remains extremely low (well below 0.01 per 10,000 participant hours); increasing age and PA intensity are associated with greater risk. In most cases of exercise-related SCD, occult CV disease is present and SCD is typically the first clinical event. Exercise acutely increases the risk of adverse CV events, with greater risk associated with vigorous intensity. The risks of an adverse CV event during and immediately after exercise are outweighed by the health benefits of vigorous exercise performed regularly. A key challenge remains the identification of occult structural heart disease and inheritable conditions that increase the chances of lethal arrhythmias during exercise. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Structural pathways and prevention of heart failure and sudden death.

PubMed

Pacifico, Antonio; Henry, Philip D

2003-07-01

We review the macroscopic and microscopic anatomy of myocardial disease associated with heart failure (HF) and sudden cardiac death (SCD) and focus on the prevention of SCD in light of its structural pathways. Compared to patients without SCD, patients with SCD exhibit 5- to 6-fold increases in the risks of ventricular arrhythmias and SCD. Epidemiologically, left ventricular hypertrophy by ECG or echocardiography acts as a potent dose-dependent SCD predictor. Dyslipidemia, a coronary disease risk factor, independently predicts echocardiographic hypertrophy. In adult SCD autopsy studies, increases in heart weight and severe coronary disease are constant findings, whereas rates of acute coronary thrombi vary remarkably. The microscopic myocardial anatomy of SCD is incompletely defined but may include prevalent changes of advanced myocardial disease, including cardiomyocyte hypertrophy, cardiomyocyte apoptosis, fibroblast hyperplasia, diffuse and focal matrix protein accumulation, and recruitment of inflammatory cells. Hypertrophied cardiomyocytes express "fetospecific" genetic programs that can account for acquired long QT physiology with risk for polymorphic ventricular arrhythmias. Structural heart disease associated with HF and high SCD risk is causally related to an up-regulation of the adrenergic renin-angiotensin-aldosterone pathway. In outcome trials, suppression of this pathway with combinations of beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, and mineralocorticoid receptor blockers have achieved substantial total mortality and SCD reductions. Contrarily, trials with ion channel-active agents that are not known to reduce structural heart disease have failed to reduce these risks. Device therapy effectively prevents SCD, but whether biventricular pacing-induced remodeling decreases left ventricular mass remains uncertain.

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

PubMed

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.

Developmental Changes in Soluble CD40 Ligand

PubMed Central

Cholette, Jill M.; Blumberg, Neil; Phipps, Richard P.; McDermott, Michael P.; Gettings, Kelly F.; Lerner, Norma B.

2008-01-01

Objectives To determine if soluble CD40 ligand (sCD40L; formally CD154) levels vary with age and to identify age-dependent ranges in healthy pediatric and adult populations. Study design sCD40L was measured in 25 neonates, 74 children (3 months –15 years) and 20 adults using an enzyme-linked immunosorbent assay. For age group comparisons, Mann-Whitney tests were performed. Correlation coefficients assessed relationships between plasma and serum sCD40L. Results Plasma sCD40L levels were higher in neonates than in all other age groups, (p<0.001). All grouped pediatric plasma levels were significantly higher than in adults (p<0.0001). There were no significant differences in plasma sCD40L between pediatric age groups. Serum levels were significantly higher in neonates than in any other age group (p <0.0001). Pediatric and adult serum sCD40L levels were not significantly different. Conclusions Plasma sCD40L levels are highest at birth and remain higher than those in adults throughout childhood. Reasons for such developmental changes remain to be investigated. Age appropriate reference ranges should be used when sCD40L is being evaluated in pediatric disorders. PMID:18154898

The prevalence of abnormal leukocyte count, and its predisposing factors, in patients with sickle cell disease in Saudi Arabia.

PubMed

Ahmed, Anwar E; Ali, Yosra Z; Al-Suliman, Ahmad M; Albagshi, Jafar M; Al Salamah, Majid; Elsayid, Mohieldin; Alanazi, Wala R; Ahmed, Rayan A; McClish, Donna K; Al-Jahdali, Hamdan

2017-01-01

High white blood cell (WBC) count is an indicator of sickle cell disease (SCD) severity, however, there are limited studies on WBC counts in Saudi Arabian patients with SCD. The aim of this study was to estimate the prevalence of abnormal leukocyte count (either low or high) and identify factors associated with high WBC counts in a sample of Saudi patients with SCD. A cross-sectional and retrospective chart review study was carried out on 290 SCD patients who were routinely treated at King Fahad Hospital in Hofuf, Saudi Arabia. An interview was conducted to assess clinical presentations, and we reviewed patient charts to collect data on blood test parameters for the previous 6 months. Almost half (131 [45.2%]) of the sample had abnormal leukocyte counts: low WBC counts 15 (5.2%) and high 116 (40%). High WBC counts were associated with shortness of breath ( P =0.022), tiredness ( P =0.039), swelling in hands/feet ( P =0.020), and back pain ( P =0.007). The mean hemoglobin was higher in patients with normal WBC counts ( P =0.024), while the mean hemoglobin S was high in patients with high WBC counts ( P =0.003). After adjustment for potential confounders, predictors of high WBC counts were male gender (adjusted odds ratio [aOR]=3.63) and patients with cough (aOR=2.18), low hemoglobin (aOR=0.76), and low heart rate (aOR=0.97). Abnormal leukocyte count was common: approximately five in ten Saudi SCD patients assessed in this sample. Male gender, cough, low hemoglobin, and low heart rate were associated with high WBC count. Strategies targeting high WBC count could prevent disease complication and thus could be beneficial for SCD patients.

CT abdominal imaging findings in patients with sickle cell disease: acute vaso-occlusive crisis, complications, and chronic sequelae.

PubMed

Gardner, Carly S; Boll, Daniel T; Bhosale, Priya; Jaffe, Tracy A

2016-12-01

Sickle cell disease (SCD) is the most prevalent hemoglobinopathy. Survival in patients with SCD has improved over the past few decades. These patients experience a lifetime of repeated acute pain crises, which are thought to result from sickling and microvascular occlusions; acute abdominal pain is common. Moreover, repeated crises often lead to organ dysfunction, such as asplenia, hepatic failure, and renal failure. The spleen, liver, biliary system, kidneys, and gastrointestinal tract can all be affected. Patients may undergo CT to further direct clinical management. We review the spectrum of CT imaging findings of abdominal manifestations in patients with SCD, from the acute microvascular occlusive pain crisis to the potential complications and chronic sequelae.

[Antidotal effects of 2,3-dimercaptopropane-1-sulfonate sodium (DMPS) and combined with diazepam on acute poisoning caused by sodium ammonium dimethyl-2-propano-1,3-dithiosulfate monohydrate (SCD)].

PubMed

Lu, Z Q; Hu, G X; Chen, Z K

1992-07-01

In mice, DMPS (250 mg/kg, i.v.) combined with diazepam (1.25 mg/kg, i.p.) could increase LD50 of p. o. SCD 5.3 times. DMPS (62.5 mg/kg, i.v.) antagonized completely the respiratory depression and neuromuscular blockade caused by SCD(7.5 mg/kg, i.v.) in rabbits. SCD (15 mg/kg, i.v.) caused tremor, tonic convulsion and the abnormal paroxysmal discharges in EEG in rabbits. DMPS (0.5 mg/kg, i.c.v) could not eliminate the abnormal paroxysmal discharges in EEG of rabbits. DMPS (62.5 mg/kg, i.v.) combined with diazepam (5 mg/kg, i.v.) completely and rapidly antagonize these toxic symptoms and the abnormal changes in EEG.

Feeding a High Concentrate Diet Down-Regulates Expression of ACACA, LPL and SCD and Modifies Milk Composition in Lactating Goats

PubMed Central

Tao, Hui; Chang, Guangjun; Xu, Tianle; Zhao, Huajian; Zhang, Kai; Shen, Xiangzhen

2015-01-01

High concentrate diets are fed to early and mid-lactation stages dairy ruminants to meet the energy demands for high milk production in modern milk industry. The present study evaluated the effects of a high concentrate diet on milk fat and milk composition, especially, cis-9, trans-11 CLA content in milk and gene expression of lactating goats. Eight mid-lactating goats with rumen fistula were randomly assigned into a high concentrate diet (HCD) group and low concentrate diet (LCD) group. High concentrate diet feeding significantly increased lipopolysaccharides (LPS) in plasma and decreased milk fat content, vaccenic acid (VA) and cis-9, trans-11 CLA in milk of the lactating goats. The mRNA expression levels of sterol regulatory element binding protein B 1c (SREBP1c), lipoprotein lipase (LPL), fatty acid synthetase (FASN) and acetyl-CoA carboxylase α (ACACA, ACCα) involving in lipid metabolism were analyzed, and ACACA and LPL all decreased in their expression level in the mammary glands of goats fed a high concentrate diet. DNA methylation rate of stearoyl-CoA desaturase (SCD) was elevated and decreased, and SCD mRNA and protein expression was reduced significantly in the mammary glands of goats fed a high concentrate diet. In conclusion, feeding a high concentrate diet to lactating goats decreases milk fat and reduced expression of SCD in the mammary gland, which finally induced cis-9, trans-11 CLA content in milk. PMID:26086219

Barriers to Care for Persons With Sickle Cell Disease: The Case Manager's Opportunity to Improve Patient Outcomes.

PubMed

Brennan-Cook, Jill; Bonnabeau, Emily; Aponte, Ravenne; Augustin, Christina; Tanabe, Paula

The purpose of this discussion is to review the barriers to care for patients with sickle cell disease (SCD). Chronic pain and the perception of addiction, implicit bias, frequent hospitalizations and emergency department visits, clinician and patient knowledge deficits, and SCD stigma all impede the ability to provide evidence-based care for patients with SCD. Case managers can coordinate and advocate for appropriate care that improves patient outcomes. This discussion is relevant to case managers working with patients with SCD in the clinic, hospital, and emergency department. Case managers can serve an important advocacy role and intervene to improve the coordination of services and efficient use of resources. This will lead to improved quality of life and optimal health care utilization for persons with SCD. As a constant member of the health care team, the case manager may be the only health care team member who has a broad knowledge of the patient's experience of acute and chronic pain, usual state of health, social behavioral health needs, and how these factors may affect both inpatient and outpatient health care use and health outcomes. This article explores the barriers to care and suggests specific interventions within the role of the case manager that can improve care delivered and ultimately contribute to improved patient outcomes. Specifically, these interventions can improve communication among members of the health care team. Case manager interventions can guide coordination, prevent hospital readmissions, reduce health care utilization, and contribute to overall improved patient quality of life and health outcomes.

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

PubMed

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.

Implantable cardioverter defibrillators in the context of hypertrophic cardiomyopathy: a lesson in patient autonomy.

PubMed

Bray, Jonathan James Hyett; Bucciarelli-Ducci, Chiara; Stuart, Graham

2018-02-05

Hypertrophiccardiomyopathy (HCM) is common, whereas the decision not to have an implantable cardioverterdefibrillator (ICD) when probably falling into a 'high-risk' category is not. A solicitor aged 45 years attended the inherited cardiac conditions clinic for review of her HCM and discussion about ICD implantation for primary prevention of sudden cardiac death (SCD). Despite a predicted 7% risk of SCD within the next 5 years, according to the European Society of Cardiology endorsed HCM Risk-SCD risk stratification tool, the patient opted against implantation of an ICD and comprehensively justifies her decision. This report discusses ethical aspects of a consultation offering ICD protection against SCD in the context of HCM and emphasises the clinicians' role in respecting patient autonomy. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

An evaluation of serum soluble CD30 levels and serum CD26 (DPPIV) enzyme activity as markers of type 2 and type 1 cytokines in HIV patients receiving highly active antiretroviral therapy

PubMed Central

Keane, N M; Price, P; Lee, S; Stone, S F; French, M A

2001-01-01

This study evaluates serum CD26 (dipeptidyl peptidase IV, DPPIV) enzyme activity and serum levels of soluble CD30 as markers of T1 and T2 cytokine environments in HIV patients who achieved immune reconstitution after highly active antiretroviral therapy (HAART). Patients who had experienced inflammatory disease associated with pre-existent opportunistic infections after HAART (immune restoration diseases, IRD) were considered separately. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were compared with IFN-γ production by PBMC cultured with cytomegalovirus (CMV) antigen in controls and patient groups. High sCD30 levels were associated with low IFN-γ production after antigenic stimulation in control subjects and, to a lesser extent, in immune reconstituted HIV patients. There was no association between serum CD26 (DPPIV) enzyme activity and IFN-γ production or sCD30 levels. Serum sCD30 levels and CD26 (DPPIV) enzyme activity were significantly increased in immune reconstituted patients with high HIV viral loads. Patients who had experienced CMV retinitis as an IRD had significantly higher sCD30 levels than all other patient groups. Hence, high sCD30 levels may be a marker of a T2 cytokine environment in HIV patients with immune reconstitution and are associated with higher HIV viral loads and a history of CMV associated IRD. PMID:11678906

Blood transfusion and 30-day readmission rate in adult patients hospitalized with sickle cell disease crisis

PubMed Central

Nouraie, Mehdi; Gordeuk, Victor R.

2015-01-01

Background Sickle cell disease (SCD) patients hospitalized with vaso-occlusive pain crisis tend to have prolonged length of stay (LOS) and high 30-day readmission rates. We investigated the associations of demographic characteristics, comorbidities and blood transfusion during hospitalization with these outcomes. Study Design Repeated regression analysis was used to analyze 39,324 admissions of 4,348 adults with sickle cell crisis from 2007–2012 in the Truven Health MarketScan® Medicaid Databases. Results The mean (95% range) LOS was 5.9 (1.0–19.0) days and the 30-day readmission rate was 39.6% (95% confidence interval [CI]: 39.1%–40.0%). Older age, chronic cardiopulmonary, renal or liver disease and sepsis were associated with both longer LOS and greater 30-day readmission rate. Female gender, iron overload, acute chest syndrome, acute renal failure and stroke were additional predictors of longer LOS. Simple red blood cell transfusion was administered in 31.3% of the admissions, and these patients tended to have more severe disease (chronic cardiopulmonary or kidney disease, acute chest syndrome, acute kidney or liver failure, sepsis). Nevertheless, transfusion was associated with a reduced estimated odds ratio of inpatient mortality of 0.75 (95% CI: 0.57–0.99) and a decreased odds ratio of 30-day readmission of 0.78 (95% CI: 0.73–0.83). Conclusion Our findings point to blood transfusion as a potential means to reduce the 30-day readmission rate among Medicaid patients hospitalized with sickle cell crisis. There is a need for a prospective study to examine the potential benefit and safety of simple blood transfusion for this purpose. PMID:26126756

Clinician assessment for acute chest syndrome in febrile patients with sickle cell disease: is it accurate enough?

PubMed

Morris, C; Vichinsky, E; Styles, L

1999-07-01

To determine whether the use of empiric chest radiography (CXR) is of significant value in detecting clinically unsuspected acute chest syndrome (ACS) in febrile patients with sickle cell disease (SCD). Patients with SCD presenting to the emergency department and hematology clinic with temperature greater than or equal to 38 degrees C were prospectively evaluated using a physician-completed questionnaire. The questionnaire included inquiries into the patient's physical signs and symptoms and the physician's clinical impression for the presence of ACS. The questionnaire was completed before obtaining CXR results in all patients. Seventy-three patients with SCD with 96 febrile events were evaluated over a 1-year period. Twenty-four percent (23/96) of the patients had CXR evidence of ACS. On the basis of the questionnaire data, 61% (14/23) of ACS cases were not clinically suspected by the evaluating physician before obtaining CXR. Comparing the patients with and without ACS revealed that, with the exception of splinting (4/23 [17%] versus 0/73 [0%]), no symptom or physical examination finding helped to identify which patients had ACS. Fifty-seven percent of patients with ACS had completely normal findings on physical examination. The presentation of patients with clinically detected versus clinically unsuspected ACS also did not differ significantly. Length of hospitalization, oxygen use, and need for transfusion were the same in both the unsuspected and detected ACS groups. Overall physician sensitivity for predicting ACS was only 39%, and diagnostic accuracy did not improve significantly with increasing levels of pediatric training. ACS is common in patients with SCD who present with fever and was grossly underestimated by evaluating physicians. History and physical examination appear to be of little value in defining which febrile patients require CXR. In view of the mortality and morbidity associated with ACS, empiric CXR should be considered when evaluating a

Caffeine Promotes Conversion of Palmitic Acid to Palmitoleic Acid by Inducing Expression of fat-5 in Caenorhabditis elegans and scd1 in Mice.

PubMed

Du, Xiaocui; Huang, Qin; Guan, Yun; Lv, Ming; He, Xiaofang; Fang, Chongye; Wang, Xuanjun; Sheng, Jun

2018-01-01

The synthesis and metabolism of fatty acids in an organism is related to many biological processes and is involved in several diseases. The effects of caffeine on fatty acid synthesis and fat storage in Caenorhabditis elegans and mice were studied. After 6 h of food deprivation, adult C. elegans were treated with 0.1 mg/mL caffeine for 24 h. Quantitative reverse-transcription polymerase chain reaction showed that, among all the genes involved in fat accumulation, the mRNA expression of fat-5 in caffeine-treated C. elegans was significantly higher than that of controls, whereas fat-6 and fat-7 displayed no significant difference. Gas chromatography-mass spectrometry was used to verify the fatty acid composition of C. elegans . Results showed that the ratio of palmitoleic acid (16:1) to that of palmitic acid (16:0) was higher in the caffeine-treated group. Several mutant strains, including those involved in the insulin-like growth factor-1, dopamine, and serotonin pathways, and nuclear hormone receptors ( nhrs ), were used to assess their necessity to the effects of caffeine. We found that mdt-15 was essential for the effects of caffeine, which was independent of nhr-49 and nhr -80. Caffeine may increase fat-5 expression by acting on mdt-15 . In high fat diet (HFD), but not in normal diet (ND) mice, caffeine induced expression of scd1 in both subcutaneous and epididymal white adipose tissue, which was consistent with the palmitoleic/palmitic ratio results by gas chromatograph analysis. In mature adipocytes, caffeine treatment induced both mRNA and protein expression of scd1 and pgc-1 α. Overall, our results provided a possible mechanism on how caffeine modulates metabolism homeostasis in vivo .

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

PubMed

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.

Noninvasive risk stratification for sudden death in asymptomatic patients with Wolff-Parkinson-White syndrome.

PubMed

Novella, John; DeBiasi, Ralph M; Coplan, Neil L; Suri, Ranji; Keller, Seth

2014-01-01

Sudden cardiac death (SCD) as the first clinical manifestation of Wolff-Parkinson-White (WPW) syndrome is a well-documented, although rare occurrence. The incidence of SCD in patients with WPW ranges from 0% to 0.39% annually. Controversy exists regarding risk stratification for patients with preexcitation on surface electrocardiogram (ECG), particularly in those who are asymptomatic. This article focuses on the role of risk stratification using exercise and pharmacologic testing in patients with WPW pattern on ECG.

Milk fatty acid unsaturation: genetic parameters and effects of stearoyl-CoA desaturase (SCD1) and acyl CoA: diacylglycerol acyltransferase 1 (DGAT1).

PubMed

Schennink, A; Heck, J M L; Bovenhuis, H; Visker, M H P W; van Valenberg, H J F; van Arendonk, J A M

2008-05-01

With regard to human health aspects of milk fat, increasing the amount of unsaturated fatty acids in milk is an important selection objective. The cow's diet has an influence on the degree of unsaturation, but literature suggests that genetics also plays a role. To estimate genetic variation in milk fatty acid unsaturation indices, milk fatty acid composition of 1,933 Dutch Holstein Friesian heifers was measured and unsaturation indices were calculated. An unsaturation index represents the concentration of the unsaturated product proportional to the sum of the unsaturated product and the saturated substrate. Intraherd heritabilities were moderate, ranging from 0.23 +/- 0.07 for conjugated linoleic acid (CLA) index to 0.46 +/- 0.09 for C16 index. We genotyped the cows for the SCD1 A293V and DGAT1 K232A polymorphisms, which are known to alter milk fatty acid composition. Both genes explain part of the genetic variation in unsaturation indices. The SCD1 V allele is associated with lower C10, C12, and C14 indices, and with higher C16, C18, and CLA indices in comparison to the SCD1 A allele, with no differences in total unsaturation index. In comparison to the DGAT1 K allele, the DGAT1 A allele is associated with lower C10, C12, C14, and C16 indices and with higher C18, CLA, and total indices. We conclude that selective breeding can contribute to higher unsaturation indices, and that selective breeding can capitalize on genotypic information of both the SCD1 A293V and the DGAT1 K232A polymorphism.

Clinical impact of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations among sickle cell disease patients of Central India.

PubMed

Nishank, Sudhansu Sekhar; Singh, Mendi Prema Shyam Sunder; Yadav, Rajiv

2013-11-01

It is known that patients with sickle cell disease (SCD) present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises and also during the steady state of the disease. We determined whether the presence of the factor prothrombin gene G20210A variant, factor V gene G1691A mutation (factor V Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms may be risk factors for vascular complications in individuals with SCD. The study involved 150 patients with sickle cell anemia and 150 healthy controls of Central India. Genotyping of three thrombophilic mutations was carried out by PCR-RFLP methods using MnlI, Hind III, and Hinf I, respectively, for factor V Leiden, prothrombin, and MTHFR mutations. Patients with SCD had significantly higher prevalence of mutant variants of MTHFR gene (28.0% heterozygotes and 14.6% homozygotes) and FVL gene (14.6% heterozygotes) as compared to normal/control individuals, but complete absence of mutant variants of prothrombin gene. The patients with SCD having mutant variants of MTHFR and FVL genes showed higher incidence of pain in chest, abdomen, and bone joints along with early age of onset of clinical manifestations as well as frequent dependence on blood transfusion than those patients with SCD having wild variants of these thrombotic genes. As compared to control subjects, SCD individuals having mutant variants of FVL and MTHFR genes had significant association with higher levels of prothrombin fragment (F1+2), D-dimer, thrombin-antithrombin (TAT), and lower level of protein C. MTHFR C677T and FVL G1691A polymorphisms may be risk factors for increased vascular complications in patient with SCD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Changes in the physiological parameters, fatty acid metabolism, and SCD activity and expression in juvenile GIFT tilapia (Oreochromis niloticus) reared at three different temperatures.

PubMed

Ma, X Y; Qiang, J; He, J; Gabriel, N N; Xu, P

2015-08-01

We evaluated the effects of rearing temperature on the composition of fatty acids and stearoyl-CoA desaturase (SCD) activity and gene expression in GIFT (genetically improved farmed tilapia) tilapia. Three triplicate groups of fish were reared for 40 days at 22, 28, or 34 °C. At the end of the trial, the final body weight of juveniles reared at 28 °C was higher than that of fish reared at 22 or 34 °C. Feed intake, feed efficiency, and the protein efficiency ratio were also higher at 28 °C. The fatty acid composition of muscle tissue differed significantly (P < 0.05) among the treatment groups. The content of SFA decreased with decreasing temperature, whereas the UFA content increased. We observed high levels of PUFA, particularly n-3 PUFAs, in fish reared at the lower temperature. Rearing at low temperature significantly (P < 0.05) increased the expression and activity of the SCD gene. Increased SCD activity and gene expression can increase the biosynthesis of MUFAs in GIFT tilapia muscle. Additionally, cold acclimation can decrease the content of TC and TG in GIFT tilapia, which can help increase cold tolerance.

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

PubMed Central

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

Multiple drilling compared with standard core decompression for avascular necrosis of the femoral head in sickle cell disease patients.

PubMed

Al Omran, Abdullah

2013-05-01

Sickle cell disease (SCD) is the most common cause of avascular necrosis of femoral head (ANFH) in childhood. Advances in medical treatment led to improved life expectancy of such patients. SCD-related ANFH frequently progress to total collapse of the femoral head necessitating hip replacement. However, SCD patient are at more risk of intra- and post-operative complications and suboptimal outcome of total hip arthroplasty. Hence, it is imperative to preserve the femoral head as long as possible. Between September 1992 and June 2007, 94 core decompression procedures were done to SCD patients who had modified Ficat stage I, IIA and IIB ANFH. Sixty one patients underwent a classical 8-mm drilling and 33 patients underwent 3.2-mm diameter MD technique. Patients were followed up for minimum of 2 years and were evaluated for clinical and Harris Hip Score improvement and for radiological progression. All 19 hips that had Ficat stage I had significant reduction of pain and improvement of Harris Hip Score. No patient has required further surgery. Among the 39 hips with Ficat IIA at time of procedure, 80 % of hips which underwent CD and 78 % of MD cases had significant reduction of pain and improvement of HHS. Those patients showed no radiographic progression of the disease. The remaining, 20 % CD and 22 % MD eventually progressed radiologically to grade III or grade IV and had HHS less than 75 at last visit. In the 36 cases with Ficat IIB, 52 % CD and 52.8 % MC had significant reduction of pain and improvement of HHS. The rest showed no improvement in pain and function, and progressed to stage IV; 11 of them underwent THA and one patient refused surgery. While multiple drilling is safer and less invasive than single coring in SCD, there is no statistically significant difference in outcome or complication rate between both procedures done for ANFH in patients with SCD.

Immunological monitoring after organ transplantation: potential role of soluble CD30 blood level measurement.

PubMed

Truong, Dinh Quang; Darwish, Ahmed A; Gras, Jérémie; Wieërs, Grégoire; Cornet, Anne; Robert, Annie; Mourad, Michel; Malaise, Jacques; de Ville de Goyet, Jean; Reding, Raymond; Latinne, Dominique

2007-06-01

Analysing the relevance of soluble CD30 (sCD30) in the bloodstream before and after transplantation may be important for the monitoring of transplant recipients. In this study, 27 patients (15 pediatric liver and 12 adult kidney graft recipients) were investigated. In the liver graft group, the patients who developed acute rejection during the first month (n=9) had a slightly higher sCD30 value on pre-transplantation baseline (day 0) and post-transplantation day 7, when compared to patients with normal graft function (n=6) (day 0: 102(1.6) U/ml versus 118(1.5) U/ml, p=0.52) and (day 7: 69(1.5) U/ml versus 83(1.6) U/ml, p=0.47). Increased serum sCD30 was shown to correlate with increased interleukin-10 circulating levels between day 0 and day 7 (r=0.53; p=0.04), whereas, no correlation could be evidenced between interferon-gamma (IFN-gamma) and sCD30 (r=0.02; p=0.47). Similarly, in the kidney transplantation group, no significant difference was found in sCD30 levels at day 0 in both groups with graft rejection or normal graft function (n=6) (85(1.3) U/ml versus 77(1.6) U/ml, p=0.66), but sCD30 decreased significantly at day 7 post-transplantation from baseline value in the rejection group (n=6) (77(1.6) versus 35(1.4); p=0.02). We conclude that increased serum sCD30 was correlated with increased IL-10 (interleukin-10) circulating levels, but not with IFN-gamma levels in the post-transplantation period. Neither pre-transplantation sCD30 nor sCD30 at day 7 post-transplantation could be correlated with acute rejection in liver graft recipient. The monitoring of sCD30 might constitute a tool to assess the risk of acute rejection in renal transplant but did not appear as a valuable mean for early immunological monitoring in the small group of liver allograft recipients patients analysed in this study.

Dietary intake and nutritional status in cancer patients; comparing adults and older adults.

PubMed

Gómez Valiente da Silva, Henyse; Fonseca de Andrade, Camila; Bello Moreira, Annie Seixas

2014-04-01

Evaluate the nutrient intake and nutritional status of food in cancer patients admitted to a university hospital, with comparison of adult and older adult age category. Cross-sectional study. This study involved cancer patients admitted to a hospital in 2010. Dietary habits were collected using a Brazilian food frequency questionnaire. Participants were divided in two groups: adults or older adults and in 4-cancer category: hematologic, lung, gastrointestinal and others. Body Mass Index evaluated nutritional status. A total of 86 patients with a mean age of 56.5 years, with 55% males and 42% older adults were evaluated. The older adult category had a higher frequency of being underweight (24.4% vs 16.3%, p < 0.01) and a lower frequency of being overweight (7% vs. 15.1%, p < 0.01) than adults. Both, adult and older adults had a high frequency of smoking, alcohol consumption and physical inactivity. The older adults had lower consumption of calories, intake of iron and folic acid. Inadequacy of vitamin intake was observed in both groups; respectively, 52%, 43%, 95%, 76% and 88% for Vitamin A, C, D, E and folic acid. The older adults had a higher folic acid and calcium inadequacy than the adults (97% vs 82%, p <0.01; 88% vs 72%, p < 0.01). There was no association of micronutrient intake with cancer, nor with nutritional status. The food intake, macro and micronutrients ingestion is insufficient among cancer individuals. Food intake of older adults was inferior, when compared to the adult category. There was a high prevalence of BMI excess in the adult group and a worst nutritional status in the older adult category. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Intravenous support for the patient in sickle cell crisis.

PubMed

Odesina, V

2001-01-01

Sickle cell episodes (otherwise known as crises) are inevitable complications of sickle cell disease (SCD). Successful management of these episodes includes hydration, medication administration, and blood transfusion. Intravenous support is an essential component in the management of sickle cell-related complications. This article gives an overview of SCD and its complications and treatments, focusing on infusion therapy support of the patient during a sickle cell episode.

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

PubMed

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

2017-06-01

To identify barriers to hydroxyurea adherence (negative beliefs, access, and/or recall barriers), and their relationship to adherence rates and health-related quality of life (HRQOL) among adolescents and young adults (AYA) with sickle cell disease (SCD). A cross-sectional survey was administered to 34 AYAs (12-22 years old) in SCD clinics from January to December 2015. Study measures included Brief Medication Questionnaire, Modified Morisky Adherence Scale 8-items, visual analog scale, and Patient Reported Outcomes Measurement Information System. Participants (59% male; 91% Black) had a median age of 13.5 years (IQR 12-18). Participants reported negative beliefs (32%), recall barriers (44%), and access barriers (32%). Participants with recall barriers reported worse pain (P=.02), fatigue (P=.05), and depression (P=.05). The number of adherence barriers inversely correlated with adherence level using ©MMAS-8 (r s =-.38, P=.02) and VAS dose (r s =-.25, P=.14) as well as MCV (r s =-.45, P=.01) and HbF% (r s =-.36, P=.05), suggesting higher hydroxyurea adherence in patients with fewer barriers. Patients with fewer barriers to hydroxyurea adherence were more likely to have higher adherence rates and better HRQOL scores. Routine assessment of hydroxyurea adherence and its related barriers could provide actionable information to improve adherence rates, HRQOL, and other clinical outcomes. © 2017 The Authors. European Journal of Haematology Published by John Wiley & Sons Ltd.

The macrophage activation marker CD163 is associated with IL28B genotype and hepatic inflammation in chronic hepatitis C virus infected patients.

PubMed

Dultz, G; Gerber, L; Zeuzem, S; Sarrazin, C; Waidmann, O

2016-04-01

Recent data highlighted the association of the macrophage activation marker CD163 with histological inflammation and fibrosis in chronic hepatitis C virus (HCV) infection. The aim of this study was to investigate the influence of successful antiviral treatment and IL28B genotypes on macrophage activation reflected by CD163 levels in HCV infected patients. In a retrospective cohort study, serum sCD163 levels were correlated with results of liver histopathology, IL28B genotyping and clinical parameters in 329 patients with HCV infection, 15 healthy controls and in 161 patients who achieved a sustained virologic response after antiviral treatment. sCD163 levels were significantly higher in patients with chronic HCV infection in comparison to healthy controls (5202 vs 896 ng/mL, P < 0.001). In the multivariate logistic regression analyses, sCD163 was independently associated with histologically determined inflammation (P = 0.043) but not with fibrosis (P = 0.091). sCD163 dropped significantly after successful antiviral treatment in comparison to baseline values (5202 vs 3093 ng/mL, P < 0.001). In the univariate analyses, sCD163 was significantly associated with IL28B genotype (C/C vs C/T+T/T) with higher values in the C/C group (6098 vs 4812 ng/mL, P = 0.003). In the multivariate logistic regression model, sCD163 levels were significantly associated with IL28B genotype (P = 0.003) and sustained virologic response (SVR) (P < 0.001). Our data support the association of activated liver macrophages with hepatic necroinflammation in chronic HCV infection as sCD163 levels drop rapidly after SVR. The irresponsiveness of IL28B minor genotypes to interferon might be related to a lower level of macrophage activation in these patients. © 2015 John Wiley & Sons Ltd.

Translating sickle cell guidelines into practice for primary care providers with Project ECHO

PubMed Central

Shook, Lisa M.; Farrell, Christina B.; Kalinyak, Karen A.; Nelson, Stephen C.; Hardesty, Brandon M.; Rampersad, Angeli G.; Saving, Kay L.; Whitten-Shurney, Wanda J.; Panepinto, Julie A.; Ware, Russell E.; Crosby, Lori E.

2016-01-01

Background Approximately 100,000 persons with sickle cell disease (SCD) live in the United States, including 15,000 in the Midwest. Unfortunately, many patients experience poor health outcomes due to limited access to primary care providers (PCPs) who are prepared to deliver evidence-based SCD care. Sickle Treatment and Outcomes Research in the Midwest (STORM) is a regional network established to improve care and outcomes for individuals with SCD living in Indiana, Illinois, Michigan, Minnesota, Ohio, and Wisconsin. Methods STORM investigators hypothesized that Project ECHO® methodology could be replicated to create a low-cost, high-impact intervention to train PCPs in evidence-based care for pediatric and young adult patients with SCD in the Midwest, called STORM TeleECHO. This approach utilizes video technology for monthly telementoring clinics consisting of didactic and case-based presentations focused on the National Heart, Lung and Blood Institute (NHLBI) evidence-based guidelines for SCD. Results Network leads in each of the STORM states assisted with developing the curriculum and are recruiting providers for monthly clinics. To assess STORM TeleECHO feasibility and acceptability, monthly attendance and satisfaction data are collected. Changes in self-reported knowledge, comfort, and practice patterns will be compared with pre-participation, and 6 and 12 months after participation. Conclusions STORM TeleECHO has the potential to increase implementation of the NHLBI evidence-based guidelines, especially increased use of hydroxyurea, resulting in improvements in the quality of care and outcomes for children and young adults with SCD. This model could be replicated in other pediatric chronic illness conditions to improve PCP knowledge and confidence in delivering evidence-based care. PMID:27887664

Cancer incidence rate and mortality rate in sickle cell disease patients at Howard University Hospital: 1986-1995.

PubMed

Dawkins, F W; Kim, K S; Squires, R S; Chisholm, R; Kark, J A; Perlin, E; Castro, O

1997-08-01

The incidence of cancer in patients with sickle cell disease (SCD) is not known. The 10-year follow-up data on 696 patients with SCD was analyzed at our institution in order to determine the cancer incidence and cancer mortality rates. The age range was 18 to 79 years, with a mean age of 28.8 years. There were 377 females and 319 males. The median follow-up was 3 years. Five patients developed cancer during this period. The cancer incidence rate was 5/2,864 or 1.74 per 1,000 patient years. The 95% CI was 0.64 to 4.32 per 1,000 patient years. There were 68 deaths with 3 being due to cancer. The cancer mortality rate was 3/2,873 or 1.04 cases per 1,000 patient years. Our data represent the first published paper that the authors are aware of, where the cancer incidence and mortality rates have been calculated for any group of patients with SCD.

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study.

PubMed

Jespersen, Sofie; Pedersen, Karin Kæreby; Anesten, Birgitta; Zetterberg, Henrik; Fuchs, Dietmar; Gisslén, Magnus; Hagberg, Lars; Trøseid, Marius; Nielsen, Susanne Dam

2016-04-21

HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver

Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients.

PubMed

Danese, S; Katz, J A; Saibeni, S; Papa, A; Gasbarrini, A; Vecchi, M; Fiocchi, C

2003-10-01

The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa. To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms. CD, UC, and normal control subjects were studied. The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC). Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets. Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.

Study of inhaler technique in asthma patients: differences between pediatric and adult patients

PubMed Central

Manríquez, Pablo; Acuña, Ana María; Muñoz, Luis; Reyes, Alvaro

2015-01-01

Objective: Inhaler technique comprises a set of procedures for drug delivery to the respiratory system. The oral inhalation of medications is the first-line treatment for lung diseases. Using the proper inhaler technique ensures sufficient drug deposition in the distal airways, optimizing therapeutic effects and reducing side effects. The purposes of this study were to assess inhaler technique in pediatric and adult patients with asthma; to determine the most common errors in each group of patients; and to compare the results between the two groups. Methods: This was a descriptive cross-sectional study. Using a ten-step protocol, we assessed inhaler technique in 135 pediatric asthma patients and 128 adult asthma patients. Results: The most common error among the pediatric patients was failing to execute a 10-s breath-hold after inhalation, whereas the most common error among the adult patients was failing to exhale fully before using the inhaler. Conclusions: Pediatric asthma patients appear to perform most of the inhaler technique steps correctly. However, the same does not seem to be true for adult patients. PMID:26578130

A validation study of the 2003 American College of Cardiology/European Society of Cardiology and 2011 American College of Cardiology Foundation/American Heart Association risk stratification and treatment algorithms for sudden cardiac death in patients with hypertrophic cardiomyopathy.

PubMed

O'Mahony, Constantinos; Tome-Esteban, Maite; Lambiase, Pier D; Pantazis, Antonios; Dickie, Shaughan; McKenna, William J; Elliott, Perry M

2013-04-01

Sudden cardiac death (SCD) is a common mode of death in hypertrophic cardiomyopathy (HCM), but identification of patients who are at a high risk of SCD is challenging as current risk stratification guidelines have never been formally validated. The objective of this study was to assess the power of the 2003 American College of Cardiology (ACC)/European Society of Cardiology (ESC) and 2011 ACC Foundation (ACCF)/American Heart Association (AHA) SCD risk stratification algorithms to distinguish high risk patients who might be eligible for an implantable cardioverter defibrillator (ICD) from low risk individuals. We studied 1606 consecutively evaluated HCM patients in an observational, retrospective cohort study. Five risk factors (RF) for SCD were assessed: non-sustained ventricular tachycardia, severe left ventricular hypertrophy, family history of SCD, unexplained syncope and abnormal blood pressure response to exercise. During a follow-up period of 11 712 patient years (median 6.6 years), SCD/appropriate ICD shock occurred in 20 (3%) of 660 patients without RF (annual rate 0.45%), 31 (4.8%) of 636 patients with 1 RF (annual rate 0.65%), 27 (10.8%) of 249 patients with 2 RF (annual rate 1.3%), 7 (13.7%) of 51 patients with 3 RF (annual rate 1.9%) and 4 (40%) of 10 patients with ≥4 RF (annual rate 5.0%). The risk of SCD increased with multiple RF (2 RF: HR 2.87, p≤0.001; 3 RF: HR 4.32, p=0.001; ≥4 RF: HR 11.37, p<0.0001), but not with a single RF (HR 1.43 p=0.21). The area under time-dependent receiver operating characteristic curves (representing the probability of correctly identifying a patient at risk of SCD on the basis of RF profile) was 0.63 at 1 year and 0.64 at 5 years for the 2003 ACC/ESC algorithm and 0.61 at 1 year and 0.63 at 5 years for the 2011 ACCF/AHA algorithm. The risk of SCD increases with the aggregation of RF. The 2003 ACC/ESC and 2011 ACCF/AHA guidelines distinguish high from low risk individuals with limited power.

Clinical Features of Adult Patients Admitted to Pediatric Wards in Japan.

PubMed

Michihata, Nobuaki; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo

2015-10-01

Pediatricians generally need to treat adult patients who require long-term care for pediatric diseases. However, little is known about the characteristics of adult patients in pediatric wards. Using a national inpatient database, the aim of this study was to determine the clinical details of adult patients admitted to pediatric wards in Japanese acute-care hospitals. We extracted all inpatients aged ≥19 years who were admitted to pediatric departments in Japan from April 2012 to March 2013. We examined the patients' main diagnoses and the use of life-supporting home medical devices. Of 417,352 patients admitted to pediatric wards during the study period, we identified 4,729 (1.1%) adult patients. The major diagnoses of the adult patients were malignancy, congenital heart disease, epilepsy, and cerebral palsy. More than 35% of the patients with cerebral palsy had a tracheostomy tube, gastrostomy tube, home central venous alimentation, or home respirator. More than 20% of patients aged ≥40 years in pediatric wards had adult diseases, including ischemic heart diseases, cerebrovascular diseases, and adult malignancy. Many adult patients in pediatric wards had adult diseases. It is essential to establish a disease-oriented support system for adults with chronic conditions that originated in their childhood. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Implantable cardioverter defibrillators for primary prevention in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

PubMed

Akel, Tamer; Lafferty, James

2017-06-01

Implantable cardioverter defibrillators (ICDs) have proved their favorable outcomes on survival in selected patients with cardiomyopathy. Although previous meta-analyses have shown benefit for their use in primary prevention, the evidence remains less robust for patients with nonischemic cardiomyopathy (NICM) in comparison to patients with coronary artery disease (CAD). To evaluate the effect of ICD therapy on reducing all-cause mortality and sudden cardiac death (SCD) in patients with NICM. PubMed (1993-2016), the Cochrane Central Register of Controlled Trials (2000-2016), reference lists of relevant articles, and previous meta-analyses. Search terms included defibrillator, heart failure, cardiomyopathy, randomized controlled trials, and clinical trials. Eligible trials were randomized controlled trials with at least an arm of ICD, an arm of medical therapy and enrolled some patients with NICM. The primary endpoint in the trials should include all-cause mortality or mortality from SCD. Hazard ratios (HRs) for all-cause mortality and mortality from SCD were either extracted or calculated along with their standard errors. Of the 1047 abstracts retained by the initial screen, eight randomized controlled trials were identified. Five of these trials reported relevant data regarding patients with NICM and were subsequently included in this meta-analysis. Pooled analysis of HRs suggested a statistically significant reduction in all-cause mortality among a total of 2573 patients randomized to ICD vs medical therapy (HR 0.80; 95% CI, 0.67-0.96; P=.02). Pooled analysis of HRs for mortality from SCD was also statistically significant (n=1677) (HR 0.51; 95% CI, 0.34-0.76; P=.001). ICD implantation is beneficial in terms of all-cause mortality and mortality from SCD in certain subgroups of patients with NICM. © 2017 John Wiley & Sons Ltd.

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

PubMed

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.

Tract specific analysis in patients with sickle cell disease

NASA Astrophysics Data System (ADS)

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.

A retrospective analysis of the cost of hospitalizations for sickle cell disease with crisis in England, 2010/11.

PubMed

Pizzo, E; Laverty, A A; Phekoo, K J; AlJuburi, G; Green, S A; Bell, D; Majeed, A

2015-09-01

Sickle cell disease (SCD) is an inherited blood disorder which may result in a broad range of complications including recurring and severe episodes of pain--sickle 'crises'--which require frequent hospitalizations. We assessed the cost of hospitalizations associated with SCD with crisis in England. Hospital Episodes Statistics data for all hospital episodes in England between 2010 and 2011 recording Sickle Cell Anaemia with Crisis as primary diagnosis were used. The total cost of admissions and exceeded length of stay due to SCD were assessed using Healthcare Resource Groups tariffs. The impact of patients' characteristics on SCD admissions costs and the likelihood of incurring extra bed days were also examined. In 2010-11, England had 6077 admissions associated with SCD with crisis as primary diagnosis. The total cost for these admissions for commissioners was £18,798 255. The cost of admissions increases with age (children admissions costs 50% less than adults). Patients between 10 and 19 years old are more likely to stay longer in hospital compared with others. SCD represents a significant cost for commissioners and the NHS. Further work is required to assess how best to manage patients in the community, which could potentially lead to a reduction in hospital admissions and length of stay, and their associated costs. © The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Associations Among Emergency Room Visits, Parenting Styles, and Psychopathology Among Pediatric Patients With Sickle Cell

PubMed Central

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

2018-01-01

Background 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). Procedures 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. Results 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. Conclusions 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. PMID:24975124

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

PubMed

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.

Non-pharmacologic management of sickle cell pain.

PubMed

Bodhise, Paul Brown; Dejoie, Marjorie; Brandon, Zemoria; Simpkins, Stanley; Ballas, Samir K

2004-06-01

Patients with sickle cell disease (SCD) suffer from both acute and chronic pain. The latter includes avascular necrosis of the hip joints mostly in the adult population. It has a negative impact on the quality of life of affected individuals and is often associated with depression, disability, unemployment and dependence on opioid analgesics. In this study, we show that a non-pharmacologic approach to management with deep tissue/deep pressure massage therapy technique, including neuromuscular trigger point treatment with acupressure, in patients with SCD has a salutary effect on pain relief and quality of life. Copyright 2004 Taylor and Francis Ltd

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

PubMed

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 < 0.05) and an increase in use of PCAs (P < 0.05). Patient readmission rates, number of transfusions, incidence of acute chest syndrome, and use of naloxone did not significantly change. Hospitalist-led 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

Influence of early maladaptive schemas, depression, and anxiety on the intensity of self-reported cognitive complaint in older adults with subjective cognitive decline.

PubMed

Tandetnik, Caroline; Hergueta, Thierry; Bonnet, Philippe; Dubois, Bruno; Bungener, Catherine

2017-10-01

Subjective cognitive decline (SCD) designates a self-reported cognitive decline despite preserved cognitive abilities. This study aims to explore, in older adults with SCD, the association between intensity of self-reported cognitive complaint and psychological factors including Young's early maladaptive schemas (EMSs) (i.e. enduring cognitive structures giving rise to beliefs about oneself and the world), as well as depression and anxiety. Seventy-six subjects (69.22 years ± 6.1) with intact cognitive functioning were recruited through an advertisement offering free participation in an intervention on SCD. After undergoing a neuropsychological examination (including global cognition (MMSE) and episodic memory (FCSRT)) and a semi-structured interview to assess depressive symptoms (MADRS), they completed a set of online self-reported questionnaires on SCD (McNair questionnaire), Young's EMSs (YSQ-short form), depression (HADS-D), and anxiety (HADS-A and trait-STAI-Y). The McNair score did not correlate with the neuropsychological scores. Instead, it was highly (r > 0.400; p < 0.005) correlated with trait anxiety and three EMSs belonging to the "Impaired autonomy and performance" domain: Dependence/incompetence, Failure to achieve and Vulnerability to harm or illness. Our final regression model comprising depression, anxiety, and these three EMSs as predictors (while controlling for age, gender, and objective cognition) accounted for 38.5% of the observed variance in SCD intensity. The level of cognitive complaint is significantly associated with Young's EMSs in the category of "Impaired autonomy and performance". We assume that SCD may primarily be driven by profound long-term inner beliefs about oneself that do not specifically refer to self-perceived memory abilities.

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

PubMed

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.

Best practices for transfusion for patients with sickle cell disease

PubMed Central

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.

Diagnosis of Adult Patients with Cystic Fibrosis.

PubMed

Nick, Jerry A; Nichols, David P

2016-03-01

The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS

PubMed Central

Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability. PMID:29155846

Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS.

PubMed

Doublier, Sophie; Zennaro, Cristina; Musante, Luca; Spatola, Tiziana; Candiano, Giovanni; Bruschi, Maurizio; Besso, Luca; Cedrino, Massimo; Carraro, Michele; Ghiggeri, Gian Marco; Camussi, Giovanni; Lupia, Enrico

2017-01-01

CD40/CD40 ligand (CD40L) dyad, a co-stimulatory bi-molecular complex involved in the adaptive immune response, has also potent pro-inflammatory actions in haematopoietic and non-haematopoietic cells. We describe here a novel role for soluble CD40L (sCD40L) as modifier of glomerular permselectivity directly acting on glomerular epithelial cells (GECs). We found that stimulation of CD40, constitutively expressed on GEC cell membrane, by the sCD40L rapidly induced redistribution and loss of nephrin in GECs, and increased albumin permeability in isolated rat glomeruli. Pre-treatment with inhibitors of CD40-CD40L interaction completely prevented these effects. Furthermore, in vivo injection of sCD40L induced a significant reduction of nephrin and podocin expression in mouse glomeruli, although no significant increase of urine protein/creatinine ratio was observed after in vivo injection. The same effects were induced by plasma factors partially purified from post-transplant plasma exchange eluates of patients with focal segmental glomerulosclerosis (FSGS), and were blocked by CD40-CD40L inhibitors. Moreover, 17 and 34 kDa sCD40L isoforms were detected in the same plasmapheresis eluates by Western blotting. Finally, the levels of sCD40Lwere significantly increased in serum of children both with steroid-sensitive and steroid-resistant nephrotic syndrome (NS), and in adult patients with biopsy-proven FSGS, compared to healthy subjects, but neither in children with congenital NS nor in patients with membranous nephropathy. Our results demonstrate that sCD40L directly modifies nephrin and podocin distribution in GECs. Moreover, they suggest that sCD40L contained in plasmapheresis eluates from FSGS patients with post-transplant recurrence may contribute, presumably cooperating with other mediators, to FSGS pathogenesis by modulating glomerular permeability.

A Randomized Trial to Compare the Safety, Tolerability, and Effectiveness of 3 Antimalarial Regimens for the Prevention of Malaria in Nigerian Patients With Sickle Cell Disease.

PubMed

Olaosebikan, Rasaq; Ernest, Kolade; Bojang, Kalifa; Mokuolu, Olugbenga; Rehman, Andrea M; Affara, Muna; Nwakanma, Davis; Kiechel, Jean-René; Ogunkunle, Taofik; Olagunju, Tope; Murtala, Rukayat; Omefe, Peter; Lambe, Tosin; Bello, Surajudeen; Ibrahim, Olayinka; Olorunsola, Benedict; Ojuawo, Ayotade; Greenwood, Brian; Milligan, Paul

2015-08-15

Malaria prophylaxis is recommended for persons with sickle cell disease (SCD), but the value of this has been questioned. The aim of this study was to find out whether intermittent preventive treatment (IPT) with a fixed-dose combination of mefloquine-artesunate (MQAS) or sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) was more effective than daily proguanil for malaria prevention in subjects with SCD. Patients with SCD were randomized to receive daily treatment with proguanil or IPT with either MQAS or SPAQ once every 2 months at routine clinic visits. Patients were followed up for 14 months. A total of 270 patients with SCD were studied, with 90 in each group. Adherence to the IPT regimens was excellent, but 57% of patients took <75% of their daily doses of proguanil. IPT was well tolerated; the most common side effects were vomiting and abdominal pain. Protective efficacy against malaria, compared with daily proguanil, was 61% (95% confidence interval, 3%-84%) for MQAS and 36% (40%-70%) for SPAQ. There were fewer outpatient illness episodes in children who received IPT than those who received proguanil. IPT with MQAS administered to patients with SCD during routine clinic visits was well tolerated and more effective in preventing malaria than daily prophylaxis with proguanil. NCT01319448 and ISRCTN46158146. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Milk fatty acid profile is modulated by DGAT1 and SCD1 genotypes in dairy cattle on pasture and strategic supplementation.

PubMed

Carvajal, A M; Huircan, P; Dezamour, J M; Subiabre, I; Kerr, B; Morales, R; Ungerfeld, E M

2016-05-09

Milk fat composition is important to consumer health. During the last decade, some fatty acids (FA) have received attention because of their functional and beneficial effects on human health. The milk FA profile is affected by both diet and genetics. Differences in milk fat composition are based on biochemical pathways, and candidate genes have been proposed to explain FA profile variation. Here, the association between DGAT1 K232A, SCD1 A293V, and LEPR T945M markers with milk fat composition in southern Chile was evaluated. We selected five herds of Holstein-Friesian, Jersey, Frisón Negro, Montbeliarde, and Overo Colorado cows (pasture-grazed) that received strategic supplementation with concentrates and conserved forages. We genotyped the SNPs and calculated allele frequencies and Hardy-Weinberg equilibrium. Milk fat composition was determined for individual milk samples over a year, and associations between genotypes and milk composition were studied. The most frequent variants for DGAT1, SCD1, and LEPR polymorphisms were GC/GC, C, and C, respectively. The DGAT1 GC/GC allele was associated with lower milk fat and protein content, lower saturated fatty acid levels, and higher polyunsaturated FA (PUFA), n-3 and n-6 FA, and a linolenic acid to cholesterolemic FA ratios, which implied a healthier FA profile. The SCD1 CC genotype was associated with a low cholesterolemic FA content, a high ratio of linolenic acid to cholesterolemic FA, and lower conjugated-linolenic acid and PUFA content. These results suggest the possible modulation of milk fat profiles, using specific genotypes, to improve the nutritional quality of dairy products.

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

PubMed

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.

Soluble CD163, a marker of Kupffer cell activation, is related to portal hypertension in patients with liver cirrhosis.

PubMed

Grønbaek, H; Sandahl, T D; Mortensen, C; Vilstrup, H; Møller, H J; Møller, S

2012-07-01

Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co-activation of hepatic stellate cells. To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis. We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child-Pugh CP-A: n = 26, CP-B: n = 29, CP-C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child-Pugh and MELD-score. In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP-score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99. Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child-Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention. © 2012 Blackwell Publishing Ltd.

Role of calcium in phosphatidylserine externalisation in red blood cells from sickle cell patients.

PubMed

Weiss, Erwin; Rees, David Charles; Gibson, John Stanley

2011-01-01

Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates Ca(2+) entry, providing an obvious link with phosphatidylserine exposure. The role of Ca(2+) was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [Ca(2+)] was increased. This effect was inhibited by dipyridamole, intracellular Ca(2+) chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K(+) saline. Ca(2+) levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with Ca(2+) entry through the deoxygenation-induced pathway (P(sickle)), activating the Gardos channel. [Ca(2+)] required for phosphatidylserine scrambling are in the range achievable in vivo.

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

PubMed

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

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

PubMed

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 (P<0.001), I-FABP (P<0.01) and sCD14 (P<0.05) in CLD when compared to healthy controls. However, the levels of cCK-18 (P<0.01) and I-FABP (P<0.01) in CLD-GFD were higher when compared with controls. Interestingly, elevated levels of cCK-18 and I-FABP were found in T2D and T1D (P<0.001), and T1D/INS (P<0.01, P<0.001). Twenty-two out of 43 CLD 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.

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

PubMed

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 < .001). The use of hydroxyurea treatment was significantly higher among the wild (AA) genotype (47%) than the heterozygous (AG; 21%) and homozygous (GG; 5%) genotypes (p = .003). We found no significant difference between our population of Egyptian SCD cases and controls regarding CD209 A>G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients. Copyright © 2017. Published by Elsevier Ltd.

Participation of family members and quality of patient care - the perspective of adult surgical patients.

PubMed

Leino-Kilpi, Helena; Gröndahl, Weronica; Katajisto, Jouko; Nurminen, Matti; Suhonen, Riitta

2016-08-01

The aim of this study is to describe the participation of family members in the care of Finnish adult surgical patients and the connection of the participation with the quality of patient care as perceived by surgical patients. The family members of adult surgical patients are important. Earlier studies vary concerning the nature of participation, its meaning and the connection of participation with patient-centred quality of care. In this study, we aim to produce new knowledge about adult surgical patients whose family members have participated in their care. This was a cross-sectional descriptive survey study. The data were collected among adult surgical patients (N = 481) before being discharged home from hospital with two instruments: the Good Nursing Care scale and the Received Knowledge of Hospital Patients. Based on the results, most adult surgical patients report that family members participate in their care. Participation was connected with received knowledge and preconditions of care, which are components of the quality of patient care. In future, testing of different solutions for improving the participation of surgical patients' family members in patient care should be implemented. Furthermore, the preconditions of family members' participation in care and the concept of participation should be analysed to emphasise the active role of family members. The results emphasised the importance of family members for the patients in surgical care. Family members' participation is connected with the quality of patient care. © 2016 John Wiley & Sons Ltd.

Soluble CD30 serum level--an adequate marker for allograft rejection of solid organs?

PubMed

Schlaf, G; Altermann, W W; Rothhoff, A; Seliger, B

2007-11-01

The CD30 molecule, a 120 kDa cell surface glycoprotein, is a member of the tumor necrosis factor receptor (TNF-R) superfamily and was originally identified on the surface of Reed-Sternberg cells and anaplastic large cell lymphomas in Hodgkin's disease patients. In addition to lymphoproliferative disorders the expression of CD30 was found in both activated CD8+ and CD4+ Th2 cells which lead to the activation of B-cells and consequently to the inhibition of the Th1-type cellular immunity. The membrane-bound CD30 molecule can be proteolytically cleaved, thereby generating a soluble form (sCD30) of about 85 kDa. Low serum levels of soluble CD30 were found in healthy humans, whereas increased sCD30 serum concentrations were detected under pathophysiological situations such as systemic lupus erythematosus, rheumatoid arthritis, certain viral infections and adult T cell leukaemia/lymphoma. In addition, it has recently been suggested that pre- or post-transplant levels of sCD30 represent a biomarker for graft rejection associated with an impaired outcome for transplanted patients. We here review (i) the current knowledge of the clinical significance of sCD30 serum levels for solid organ transplantations and (ii) our own novel data regarding inter- and intra-individual variations as well as time-dependent alterations of sCD30 levels in patients. (iii) Based on this information the implementation of sCD30 as predictive pre-transplant or post-transplant parameter for solid organ transplantation is critically discussed.

Characterization of opioid use in sickle cell disease.

PubMed

Han, Jin; Zhou, Jifang; Saraf, Santosh L; Gordeuk, Victor R; Calip, Gregory S

2018-05-01

Opioid analgesics are commonly used to treat vaso-occlusive pain episodes in sickle cell disease (SCD), but comprehensive evidence characterizing opioid use in this patient population is limited. Our objective was to characterize opioid use patterns among SCD patients using a large nationwide database. A large, US medical claims database was utilized to identify a cohort of 3882 SCD patients, and characteristics of opioid use were analyzed. Clinical variables including age, gender, medication use, health care utilization, and medical history were evaluated for correlations with opioid use. Forty percent of patients took opioid medications during a 12-month span, and the prevalence of any opioid use was highest for 20 to 29-year-old patients (58%). The median daily opioid dose was 1.85 mg (interquartile range: 0.62-10.68 mg) oral morphine equivalents (OME). While most opioid users took between 0 and 5 mg OME daily, 3% of pediatric patients and 23% of adult patients used more than 30-mg OME daily. High-dose opioid use was associated with older age, hydroxyurea therapy, nonsteroidal anti-inflammatory drug (NSAID) use, and frequent inpatient hospitalizations. In multivariable-adjusted analyses, patients with vaso-occlusive complications such as pain crisis (OR = 3.8, 95% CI 2.7-5.3) and avascular necrosis (AVN) (OR = 3.7, 95% CI 2.7-5.1) were associated with high-dose opioid use. Our study showed that only 40% SCD patients were on opioid analgesics during a 12-month span. However, a non-trivial number of patients used a much higher dose of opioids despite a relatively low average daily opioid dose among SCD patients, particularly with vaso-occlusive complications. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed

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: <1year to 29years) at a mean therapeutic dose of 18±4.7mg/kg/day. Hydroxyurea was associated with a significant increase in mean total and fetal hemoglobin and a significant decrease in mean hemoglobin S, white blood and platelet counts, and lactate dehydrogenase levels. Hydroxyurea was associated with a significant reduction in the incidence of acute chest syndrome (-29.3%, p<0.001), vaso-occlusive 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.

Survival of Patients Receiving a Primary Prevention Implantable Cardioverter-Defibrillator in Clinical Practice vs Clinical Trials

PubMed Central

Al-Khatib, Sana M.; Hellkamp, Anne; Bardy, Gust H.; Hammill, Stephen; Jackson Hall, W.; Mark, Daniel B.; Anstrom, Kevin J.; Curtis, Jeptha; Al-Khalidi, Hussein; Curtis, Lesley H.; Heidenreich, Paul; Peterson, Eric D.; Sanders, Gillian; Clapp-Channing, Nancy; Lee, Kerry L.; Moss, Arthur J.

2013-01-01

Importance Randomized clinical trials have shown that implantable cardioverter-defibrillator (ICD) therapy saves lives. Whether the survival of patients who received an ICD in primary prevention clinical trials differs from that of trial-eligible patients receiving a primary prevention ICD in clinical practice is unknown. Objective To determine whether trial-eligible patients who received a primary prevention ICD as documented in a large national registry have a survival rate that differs from the survival rate of similar patients who received an ICD in the 2 largest primary prevention clinical trials, MADIT-II (n=742) and SCD-HeFT (n=829). Design, Setting, and Patients Retrospective analysis of data for patients enrolled in the National Cardiovascular Data Registry ICD Registry between January 1, 2006, and December 31, 2007, meeting the MADIT-II criteria (2464 propensity score–matched patients) or the SCD-HeFT criteria (3352 propensity score–matched patients). Mortality data for the registry patients were collected through December 31, 2009. Main Outcome Measures Cox proportional hazards models were used to compare mortality from any cause. Results The median follow-up time in MADIT-II, SCD-HeFT, and the ICD Registry was 19.5, 46.1, and 35.2 months, respectively. Compared with patients enrolled in the clinical trials, patients in the ICD Registry were significantly older and had a higher burden of comorbidities. In the matched cohorts, there was no significant difference in survival between MADIT-II–like patients in the registry and MADIT-II patients randomized to receive an ICD (2-year mortality rates: 13.9% and 15.6%, respectively; adjusted ICD Registry vs trial hazard ratio, 1.06; 95% CI, 0.85–1.31; P=.62). Likewise, the survival among SCD-HeFT–like patients in the registry was not significantly different from survival among patients randomized to receive ICD therapy in SCD-HeFT (3-year mortality rates: 17.3% and 17.4%, respectively; adjusted registry

Genome-Wide Association Study Singles Out SCD and LEPR as the Two Main Loci Influencing Intramuscular Fat Content and Fatty Acid Composition in Duroc Pigs

PubMed Central

Ros-Freixedes, Roger; Gol, Sofia; Pena, Ramona N.; Tor, Marc; Ibáñez-Escriche, Noelia; Dekkers, Jack C. M.; Estany, Joan

2016-01-01

Intramuscular fat (IMF) content and fatty acid composition affect the organoleptic quality and nutritional value of pork. A genome-wide association study was performed on 138 Duroc pigs genotyped with a 60k SNP chip to detect biologically relevant genomic variants influencing fat content and composition. Despite the limited sample size, the genome-wide association study was powerful enough to detect the association between fatty acid composition and a known haplotypic variant in SCD (SSC14) and to reveal an association of IMF and fatty acid composition in the LEPR region (SSC6). The association of LEPR was later validated with an independent set of 853 pigs using a candidate quantitative trait nucleotide. The SCD gene is responsible for the biosynthesis of oleic acid (C18:1) from stearic acid. This locus affected the stearic to oleic desaturation index (C18:1/C18:0), C18:1, and saturated (SFA) and monounsaturated (MUFA) fatty acids content. These effects were consistently detected in gluteus medius, longissimus dorsi, and subcutaneous fat. The association of LEPR with fatty acid composition was detected only in muscle and was, at least in part, a consequence of its effect on IMF content, with increased IMF resulting in more SFA, less polyunsaturated fatty acids (PUFA), and greater SFA/PUFA ratio. Marker substitution effects estimated with a subset of 65 animals were used to predict the genomic estimated breeding values of 70 animals born 7 years later. Although predictions with the whole SNP chip information were in relatively high correlation with observed SFA, MUFA, and C18:1/C18:0 (0.48–0.60), IMF content and composition were in general better predicted by using only SNPs at the SCD and LEPR loci, in which case the correlation between predicted and observed values was in the range of 0.36 to 0.54 for all traits. Results indicate that markers in the SCD and LEPR genes can be useful to select for optimum fatty acid profiles of pork. PMID:27023885

Asperger Syndrome: a frequent comorbidity in first diagnosed adult ADHD patients?

PubMed

Roy, Mandy; Ohlmeier, Martin D; Osterhagen, Lasse; Prox-Vagedes, Vanessa; Dillo, Wolfgang

2013-06-01

Because adult ADHD is often accompanied by psychiatric comorbidities, the diagnostic process should include a thorough investigation for comorbid disorders. Asperger-Syndrome is rarely reported in adult ADHD and commonly little attention is paid to this possible comorbidity. We investigated 53 adult ADHD-patients which visited our out patient clinic for first ADHD-diagnosis (17 females, 36 males; range of age: 18-56 years) for the frequency of a comorbid Asperger-Syndrome. Diagnosis of this autism-spectrum disorder was confirmed by applying the appropriate DSM-IV-criteria. Additionally we tested the power of the two screening-instruments "Autism-spectrum quotient" (AQ) and "Empathy quotient" (EQ) by Baron-Cohen for screening Asperger-Syndrome in adult ADHD. Eight ADHD-patients were diagnosed with a comorbid Asperger-Syndrome (15.1%). The difference in AQ- and EQ-scores between pure ADHD-patients and comorbid patients was analysed, showing significantly higher scores in AQ and significant lower scores in EQ in comorbid patients. Results show that the frequency of Asperger-Syndrome seems to be substantially increased in adult ADHD (versus the prevalence of 0.06% in the general population), indicating that investigators of adult ADHD should also be attentive to autism-spectrum disorders. Especially the AQ seems to be a potential screening instrument for Asperger-Syndrome in adult ADHD-patients.

Brief Report: CD14brightCD16- monocytes and sCD14 level negatively associate with CD4-memory T-cell frequency and predict HCV-decline on therapy.

PubMed

Judge, Chelsey J; Sandberg, Johan K; Funderburg, Nicholas T; Sherman, Kenneth E; Butt, Adeel A; Kang, Minhee; Landay, Alan L; Lederman, Michael M; Anthony, Donald D

2016-11-01

During HIV+ hepatitis C virus (HCV)+ coinfection CD14CD16 monocytes produce soluble immune-activation markers that predict disease progression and poor response to interferon (IFN)-α treatment. We evaluated relationships among immune activation, monocyte phenotype, CD4-memory T cells, and HCV-, cytomegalovirus-, and cytomegalovirus/Epstein-Barr virus/influenza-specific IFN-γ-response before and during IFN-α treatment. Effector-memory and central-memory CD4 T-cell frequencies were lower in HCV+ HIV+ donors than in uninfected donors and correlated negatively with HCV level, CD14CD16 monocytes, and plasma sCD14. sCD14 and CD14CD16 monocytes negatively correlated with IFN-α-dependent HCV decline. CD4 effector-memory T cells positively associated with cytomegalovirus/Epstein-Barr virus/influenza(CEF)-specific IFN-γ response, while sCD14 negatively associated with both CD4 effector-memory T cells and CEF-specific IFN-γ response. These data support a role for memory-CD4 T cells in HCV containment and link immune activation and CD14CD16-monocyte frequency to the failure of IFN-dependent HCV clearance.

Early maladaptive schemas in adult patients with attention deficit hyperactivity disorder.

PubMed

Philipsen, Alexandra; Lam, Alexandra P; Breit, Sigrid; Lücke, Caroline; Müller, Helge H; Matthies, Swantje

2017-06-01

The main purpose of this study was to examine whether adult patients with attention deficit hyperactivity disorder (ADHD) demonstrate sets of dysfunctional cognitive beliefs and behavioural tendencies according to Jeffrey Young's schema-focused therapy model. Sets of dysfunctional beliefs (maladaptive schemas) were assessed with the Young Schema Questionnaire (YSQ-S2) in 78 adult ADHD patients and 80 control subjects. Patients with ADHD scored significantly higher than the control group on almost all maladaptive schemas. The 'Failure', 'Defectiveness/Shame', 'Subjugation' and 'Emotional Deprivation' schemas were most pronounced in adult ADHD patients, while only 'Vulnerability to Harm or Illness' did not differ between the two groups. The schemas which were most pronounced in adult patients with ADHD correspond well with their learning histories and core symptoms. By demonstrating the existence of early maladaptive schemas in adults suffering from ADHD, this study suggests that schema theory may usefully be applied to adult ADHD therapy.

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.

PubMed

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.

Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease.

PubMed

Nickel, Robert Sheppard; Winkler, Anne M; Horan, John T; Hendrickson, Jeanne E

2016-09-01

Alloimmunization to red blood cell (RBC) antigens after transfusion is well described in patients with sickle cell disease (SCD). We recently demonstrated that leukocyte-reduced RBC transfusions appeared to induce human leukocyte antigen (HLA) antibodies in some children with SCD; now, we hypothesize that residual platelets contained in transfused RBC products may lead to platelet glycoprotein antibody formation. A cross-sectional study was conducted among never pregnant pediatric patients with SCD who either had received many RBC transfusions or had never received any transfusions. Serum was tested for antibodies to platelet-specific glycoproteins using a commercial enzyme immunoassay. Platelet-specific glycoprotein antibodies were found in 12 of 90 patients (13%) in the transfused group versus 5 of 24 patients (21%) in the never transfused group (p = 0.35). The prevalence of antibodies as well as the median standardized optical density for these two groups was not significantly different for any of the studied platelet glycoprotein antigens. There was no association with the presence of platelet-specific glycoprotein antibodies with either RBC or HLA antibodies. Leukocyte-reduced RBC transfusions do not appear to induce platelet-specific glycoprotein antibodies. The positive platelet-specific glycoprotein antibody results from this study may represent platelet autoantibodies, platelet alloantibodies, or false-positive reactions. A better understanding of the immunobiology of patients with SCD at baseline and after blood product exposure may help improve future transfusion and transplantation. © 2016 AABB.

Prognostic role of post-infarction C-reactive protein in patients undergoing implantation of cardioverter-defibrillators: design of the C-reactive protein Assessment after Myocardial Infarction to GUide Implantation of DEfibrillator (CAMI GUIDE) study.

PubMed

Bellocci, Fulvio; Biasucci, Luigi M; Gensini, Gian Franco; Padeletti, Luigi; Raviele, Antonio; Santini, Massimo; Giubilato, Giovanna; Landolina, Maurizio; Biondi-Zoccai, Giuseppe; Raciti, Giovanni; Sassara, Massimo; Castro, Antonello; Kheir, Antoine; Crea, Filippo

2007-04-01

Patients at risk of sudden cardiac death (SCD) after myocardial infarction (MI) can currently be offered effective means of prevention, such as implantable cardioverter-defibrillators (ICD). However, predictors of SCD able to identify those patients who are at higher risk are still lacking. Whether C-reactive protein (CRP), a serum inflammatory marker with established prognostic accuracy after MI, can also be a predictor of SCD is unclear. The CAMI GUIDE study is designed to evaluate the prognostic role of CRP in patients undergoing ICD implantation after MI according to MADIT II criteria (i.e. left ventricular ejection fractionSCD after MI. CRP will be measured on the basis of a pre-specified cut-off value of 3 mg/l, before and 1 month after ICD implantation; clinical follow-up will last 24 months. The primary endpoint is the combined rate of SCD or fast ventricular tachycardia/ventricular fibrillation. Secondary endpoints will be total mortality, death due to acute coronary syndromes, death from pump failure, non-fatal MI, coronary revascularization, hospitalization for congestive heart failure or unstable angina and inappropriate ICD shocks. Twenty-four Italian centers will participate in enrollment of the 290 patients planned according to power analysis. The CAMI GUIDE study will assess the predictive role of CRP in SCD in patients with previous MI undergoing ICD implantation. Its results will improve risk stratification, thereby enabling better-tailored and more cost-effective therapies to be undertaken in those patients whose need is greatest.

Patient engagement in research with older adults with cancer.

PubMed

Puts, Martine T E; Sattar, Schroder; Ghodraty-Jabloo, Vida; Hsu, Tina; Fitch, Marg; Szumacher, Ewa; Ayala, Ana Patricia; Alibhai, Shabbir M H

2017-11-01

Cancer is a disease that mostly affects older adults. Older adults have been under-represented in clinical cancer research. Around the world there is a push for patient engagement on study teams as it is anticipated to improve study design, recruitment and dissemination of findings. In the current overview we examined the evidence with regard to: 1) the history of patient engagement in research and frameworks developed; 2) impact of patient engagement on patient and research outcomes; 3) use of patient engagement in geriatrics and oncology, 4) recommendations for successful engagement; and 5) gaps in the literature that should be studied further. A narrative review was conducted. Articles published in English were searched in Medline with the help of a librarian. Patient engagement has been shown to improve the conduct of studies by making the study design more relevant and feasible, and improving recruitment rates and uptake of research findings by patients. However, the best way to engage patients is not clear yet. Several resources have been developed to support researchers engaging older adults with cancer in research. While patient engagement in research seems promising to improve study outcomes, little evidence is available thus far in geriatric oncology settings. Several gaps in the literature are identified that should be further studied to determine the value of, and best approaches to, patient engagement with older adults with cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Wen, Jianguo; Tao, Wenjing; Hao, Suyang; Zu, Youli

2017-06-13

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. 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. 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. This study is an exploration of genome editing of SCD HSPCs.

Hepatic macrophage activation and the LPS pathway in patients with alcoholic hepatitis: a prospective cohort study.

PubMed

Sandahl, Thomas Damgaard; Grønbaek, Henning; Møller, Holger Jon; Støy, Sidsel; Thomsen, Karen Luise; Dige, Anders Kirch; Agnholt, Jørgen; Hamilton-Dutoit, Stephen; Thiel, Steffen; Vilstrup, Hendrik

2014-11-01

Inflammatory activation of resident hepatic macrophages (Kupffer cells) by portal-derived lipopolysaccharide (LPS) has a primary role in animal models of alcoholic liver disease, but it has not been systematically or longitudinally studied in human alcoholic hepatitis (AH). We followed 50 patients with AH for 30 days. 26 patients with stable alcoholic cirrhosis and 20 healthy individuals were controls. We measured the plasma (P) concentrations of soluble CD163 (sCD163; a specific marker of inflammatory macrophage activation) and the expression of CD163 in liver tissue by immunohistochemistry and stereology of liver biopsies. We also measured the key components of the LPS pathway, P-LPS, sCD14, and LPS-binding protein (LBP), by enzyme-linked immunosorbent assay (ELISA). The 84-day mortality was registered. At study entry, the sCD163 concentration was 10-fold higher than in the healthy controls and 30% higher than in the stable cirrhotics (P<0.002), and it correlated with the Glasgow Alcoholic Hepatitis, Model for End-stage Liver Disease, and Child-Pugh scores (r>0.35, P<0.02, all). The liver biopsies confirmed markedly increased CD163 staining (P<0.01). P-LPS, P-CD14, and P-LBP were increased to the same degree as sCD163. During the follow-up, the sCD163 and LPS pathway components all decreased by ∼25% (P<0.05) but remained higher than in both control groups. sCD163 was an independent predictor of the 84-day mortality. The hepatic inflammation of human AH involves marked activation of hepatic macrophages, likely via the LPS pathway. Hepatic macrophages may thus present a target for biological therapy of AH.

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

PubMed

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

Tissue and Animal Models of Sudden Cardiac Death

PubMed Central

Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

2015-01-01

Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

Assessment of motivation and psychological characteristics of adult orthodontic patients.

PubMed

Pabari, Sona; Moles, David R; Cunningham, Susan J

2011-12-01

In recent years, the demand for adult orthodontic treatment has grown rapidly; yet there is a paucity of information on this subgroup of patients. It is well known that understanding the psychological characteristics and motives of any patient is fundamental and that these factors might affect patient satisfaction and adherence with treatment. There is therefore a need for clinicians to improve their understanding of this subgroup to enhance the patient's experience of treatment delivery and to increase the potential for a successful treatment outcome. The aim of this study was to develop a measure for the assessment of motivating factors and psychological characteristics of adults seeking orthodontic treatment. This study involved the qualitative development of a valid patient-centered questionnaire to assess motivating factors for adults seeking orthodontic treatment. This was achieved through semi-structured in-depth interviews; key themes were identified and used to construct a questionnaire assessing motivation for treatment. This was then combined with 3 previously validated questionnaires to measure self-esteem, anxiety or depression, and body image and facial body image. The questionnaire was distributed to 172 adult orthodontic patients at different stages of treatment in a large teaching hospital in the United Kingdom. In addition, the self-esteem, body image, and facial body image scores were compared with data on orthognathic patients from the same hospital and with data from members of the general public. Desire to straighten the teeth and improve the smile were the key motivating factors for the adult group studied. Other motives included to improve the bite, improve facial appearance, and close (dental) spacing. With respect to the psychological characteristics of self-esteem, body image, and facial body image, the adult orthodontic group was comparable with the general public. However, differences were noted when comparing data from the adult

Diffuse skull base/cervical fusion syndromes in two siblings with spondylocostal dysostosis syndrome: analysis via three dimensional computed tomography scanning.

PubMed

Al Kaissi, Ali; Ben Chehida, Farid; Ben Ghachem, Maher; Klaushofer, Klaus; Grill, Franz

2008-06-01

A study on a pair of male sibs to reach for the etiological understanding of unusual skull base/spine maldevelopment. Previously, radiographs alone were used to formulate this diagnosis. Here, three-dimensional computed tomography (3D CT) studies further clarified the typical diagnostic findings associated with spondylocostal dysostosis (SCD). Interestingly, patients with SCD are at increased risk for diffuse skull base/cervical fusion syndromes and can result in severe neurologic deficits associated with any degree of trauma. Classically SCD is defined as a skeletal dysplasia with clinical and radiologic manifestations, consisting of short neck and trunk, nonprogressive scoliosis and abnormalities of vertebral segmentation and of the ribs. Radiograms have been adopted as the only modality for the classification and prognostication of patients with SCD. Detailed clinical and radiographic examinations were undertaken with emphasis on the significance of the 3D CT scanning. We observed extensive fusion of the clivus with the cervical/entire spine, resulting in a remarkable solid, immobile, and fixed bony ankylosis of extremely serious outcome. Patients with spondylcostal dysostosis are predisposed to develop extensive skull-base-cervical spine fusion. The latter might lead to the development of a solid, immobile, and fixed bony ankylosis. In children/adults trivial injuries and/or high-energy trauma can lead to serious intracranial and spinal cord injury. Comprehensive orthopedic and neurosurgeons management must follow the recognition of these anomalies. To the best of our knowledge, no previous CT studies of the spine have been published in patients with SCD.

Mechanistic insights and characterization of sickle cell disease-associated cardiomyopathy.

PubMed

Desai, Ankit A; Patel, Amit R; Ahmad, Homaa; Groth, John V; Thiruvoipati, Thejasvi; Turner, Kristen; Yodwut, Chattanong; Czobor, Peter; Artz, Nicole; Machado, Roberto F; Garcia, Joe G N; Lang, Roberto M

2014-05-01

Cardiovascular disease is an important cause of morbidity and mortality in sickle cell disease (SCD). We sought to characterize sickle cell cardiomyopathy using multimodality noninvasive cardiovascular testing and identify potential causative mechanisms. Stable adults with SCD (n=38) and healthy controls (n=13) prospectively underwent same day multiparametric cardiovascular magnetic resonance (cine, T2* iron, vasodilator first pass myocardial perfusion, and late gadolinium enhancement imaging), transthoracic echocardiography, and applanation tonometry. Compared with controls, patients with SCD had severe dilation of the left ventricle (124±27 vs 79±12 mL/m(2)), right ventricle (127±28 vs 83±14 mL/m(2)), left atrium (65±16 vs 41±9 mL/m(2)), and right atrium (78±17 vs 56±17 mL/m(2); P<0.01 for all). Patients with SCD also had a 21% lower myocardial perfusion reserve index than control subjects (1.47±0.34 vs 1.87±0.37; P=0.034). A significant subset of patients with SCD (25%) had evidence of late gadolinium enhancement, whereas only 1 patient had evidence of myocardial iron overload. Diastolic dysfunction was present in 26% of patients with SCD compared with 8% in controls. Estimated filling pressures (E/e', 9.3±2.7 vs 7.3±2.0; P=0.0288) were higher in patients with SCD. Left ventricular dilation and the presence of late gadolinium enhancement were inversely correlated to hepatic T2* times (ie, hepatic iron overload because of frequent blood transfusions; P<0.05 for both), whereas diastolic dysfunction and increased filling pressures were correlated to aortic stiffness (augmentation pressure and index, P<0.05 for all). Sickle cell cardiomyopathy is characterized by 4-chamber dilation and in some patients myocardial fibrosis, abnormal perfusion reserve, diastolic dysfunction, and only rarely myocardial iron overload. Left ventricular dilation and myocardial fibrosis are associated with increased blood transfusion requirements, whereas left ventricular

[Qualitative research on pain experiences of adult burn patients].

PubMed

Li, L; Pan, Q; Xu, L; Lin, R Q; Dai, J X; Chen, Z H

2018-03-20

Objective: To explore the pain experiences of adult burn patients so as to lay foundation for practical analgesic measures. Methods: Using phenomenological method in qualitative research, semi-structured interviews were conducted on 12 adult burn patients hospitalized in our burn units from May to November 2015, aiming at pain experiences from immediately after burns to 3 to 7 months after being discharged from hospital. Then the Colaizzi's analysis method was applied to analyze, induce, and refine themes of interview data. Results: After analysis, pain experiences of adult burn patients were generalized into 6 themes: deep pain experiences, heavy psychological burden, limited daily life, poor assessment and treatment of pain, different attributions of pain, and different ways of coping of pain. Conclusions: Burn pain brings harm to the patients' physiology, mentality, and daily life. Nevertheless, pain processing modes of medical staff and patients themselves are the key factors affecting patients' pain experiences. Therefore, according to the deficiency of current situation of pain management, the targeted analgesic intervention measures should be carried out from the perspectives of medical staff and patients.

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).

PubMed

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.

Developmental deficits in adult patients with arteriovenous malformations.

PubMed

Lazar, R M; Connaire, K; Marshall, R S; Pile-Spellman, J; Hacein-Bey, L; Solomon, R A; Sisti, M B; Young, W L; Mohr, J P

1999-01-01

Cerebral arteriovenous malformations (AVMs) are congenital masses of arteries and veins that appear to undergo an unclear "maturation" for many years. Using structured interviews, we compared developmental history of adult patients with AVM with a comparison group of patients with cerebral tumor or aneurysm. To determine whether a remote history of developmental abnormality in adult patients with AVM might be an early marker of cerebral status. Adult patients with AVM and a comparison group of patients with cerebral aneurysm or low-grade tumor participated in a survey. Urban medical school-based tertiary care center. Forty-four randomly selected patients with AVM from the Columbia-Presbyterian AVM Database. There were 32 comparison patients:15 randomly chosen patients from the institution's Cerebral Aneurysm Database and all 17 patients who underwent a biopsy from 1990 to 1995 with a diagnosis of low-grade tumor and who could be contacted. A brief, structured interview adapted from the Centers for Disease Control and Prevention for its 1994 study of the prevalence of learning disabilities in American children. We defined the positive occurrence of a condition as an affirmative answer to the question, " Did have (condition) during his/her school-age years?" Each patient was also asked if there had been any problems in the following skill areas: reading, writing, listening, speaking, attention, impulsivity, organization, mathematics, or drawing. The AVM size was calculated on the angiographic film by measuring its longest diameter in any dimension. Patients with AVM were significantly more likely to report a positive occurrence to any survey question (P<.05). Two thirds of all patients with AVM (66%) reported at least 1 skill difficulty during their school years, significantly more than the comparison group (P<.001). Neither the maximum AVM diameter nor the occurrence of hemorrhage as an adult differed between patients with AVM with and without early skill difficulty

Transition Needs of Adolescents With Sickle Cell Disease

PubMed Central

Abel, Regina A.; Cho, Esther; Chadwick-Mansker, Kelley R.; D’Souza, Natalia; Housten, Ashley J.

2015-01-01

OBJECTIVE. This article describes how adolescents with sickle cell disease (SCD) perceive their ability to perform everyday tasks required for transition to adult health care and independent living. METHOD. The Adolescent Autonomy Checklist (AAC) was adapted to include skills associated with managing SCD (AAC–SCD) and was administered to adolescents during clinic visits. Participants indicated “can do already” or “needs practice” for 100 activities in 12 categories. RESULTS. Of 122 patients, the percentage of adolescents who needed practice was greatest in living arrangements (38.7%), money management (35.8%), vocational skills (29.6%), and health care skills (25.5%). We found a significant effect of age and of cerebrovascular injury on the percentage of those who reported “needs practice” in multiple categories. We found no effect of gender and limited effect of hemoglobin phenotype on any skill category. CONCLUSION. Findings support the need for educational intervention to improve transition skills in adolescents with SCD. PMID:26122692

Transition Needs of Adolescents With Sickle Cell Disease.

PubMed

Abel, Regina A; Cho, Esther; Chadwick-Mansker, Kelley R; D'Souza, Natalia; Housten, Ashley J; King, Allison A

2015-01-01

This article describes how adolescents with sickle cell disease (SCD) perceive their ability to perform everyday tasks required for transition to adult health care and independent living. The Adolescent Autonomy Checklist (AAC) was adapted to include skills associated with managing SCD (AAC-SCD) and was administered to adolescents during clinic visits. Participants indicated "can do already" or "needs practice" for 100 activities in 12 categories. Of 122 patients, the percentage of adolescents who needed practice was greatest in living arrangements (38.7%), money management (35.8%), vocational skills (29.6%), and health care skills (25.5%). We found a significant effect of age and of cerebrovascular injury on the percentage of those who reported "needs practice" in multiple categories. We found no effect of gender and limited effect of hemoglobin phenotype on any skill category. Findings support the need for educational intervention to improve transition skills in adolescents with SCD. Copyright © 2015 by the American Occupational Therapy Association, Inc.

Systematic review of surgical treatment techniques for adult and pediatric patients with pectus excavatum

PubMed Central

2014-01-01

This compares outcome measures of current pectus excavatum (PEx) treatments, namely the Nuss and Ravitch procedures, in pediatric and adult patients. Original investigations that stratified PEx patients based on current treatment and age (pediatric = 0–21; adult 17–99) were considered for inclusion. Outcome measures were: operation duration, analgesia duration, blood loss, length of stay (LOS), outcome ratings, complications, and percentage requiring reoperations. Adult implant patients (18.8%) had higher reoperation rates than adult Nuss or Ravitch patients (5.3% and 3.3% respectively). Adult Nuss patients had longer LOS (7.3 days), more strut/bar displacement (6.1%), and more epidural analgesia (3 days) than adult Ravitch patients (2.9 days, 0%, 0 days). Excluding pectus bar and strut displacements, pediatric and adult Nuss patients tended to have higher complication rates (pediatric - 38%; adult - 21%) compared to pediatric and adult Ravitch patients (12.5%; 8%). Pediatric Ravitch patients clearly had more strut displacements than adult Ravitch patients (0% and 6.4% respectively). These results suggest significantly better results in common PEx surgical repair techniques (i.e. Nuss and Ravitch) than uncommon techniques (i.e. Implants and Robicsek). The results suggest slightly better outcomes in pediatric Nuss procedure patients as compared with all other groups. We recommend that symptomatic pediatric patients with uncomplicated PEx receive the Nuss procedure. We suggest that adult patients receive the Nuss or Ravitch procedure, even though the long-term complication rates of the adult Nuss procedure require more investigation. PMID:24506826

A 3-year study of deferasirox therapy in sickle cell disease patients in Basra, Southern Iraq.

PubMed

Mohsin, A M; Hassan, M K

2018-06-01

Patients with sickle cell disease (SCD) may require repeated transfusions, which inevitably lead to iron overload (IOL). : This study aims to assess the effectiveness and safety of oral deferasirox (DFX) in patients with SCD and transfusional IOL. A descriptive study has been performed on patients with SCD who have completed at least 3 years on DFX. Height and weight were checked every 3-6 months. The efficacy was assessed based on serum ferritin (SF) levels. The safety was assessed based on adverse events (AEs), alanine aminotransferase (ALT), and serum creatinine (S. Cr) levels. : A total of 102 patients (61 males and 41 females) were recruited. Their mean daily iron intake was 0.13 ± 0.06 mg/kg. SF levels declined significantly from 2434.1 ± 132.9 ng/ml at the start of the study to 1655.8 ± 154.2 ng/ml at the end of the study (P < 0.05), with significant decreases observed after increasing the DFX dose to ≥ 30 mg/kg/day. ALT (12.8 ± 9.9 vs. 12.1 ± 7.1 U/L) and S. Cr (72.4 ± 9.2 vs. 74.1 ± 7.9 mmol/L) levels did not show significant differences from the start to the end of the study (P > 0.05). Thirty-eight patients (37%) developed AEs. The most common were abdominal pain (24.5%), diarrhea (8.0%), and nausea (7.8%). AEs were predominantly transient and mild to moderate in nature. This study has revealed that DFX is a safe, tolerable, and effective drug for reducing IOL in SCD patients, though it is associated with mild and transient adverse events.

4-Bicyclic heteroaryl-piperidine derivatives as potent, orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: urea-based analogs.

PubMed

Yang, Shyh-Ming; Tang, Yuting; Zhang, Rui; Lu, Huajun; Kuo, Gee-Hong; Gaul, Michael D; Li, Yaxin; Ho, George; Conway, James G; Liang, Yin; Lenhard, James M; Demarest, Keith T; Murray, William V

2013-12-15

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure-activity relationships focused on bicyclic heteroarenes and aminothiazole-urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Somatization in the conceptualization of sickle cell disease.

PubMed

Wellington, Chanté; Edwards, Christopher L; McNeil, Janice; Wood, Mary; Crisp, Benjamin; Feliu, Miriam; Byrd, Goldie; McDougald, Camela; Edwards, Lekisha; Whitfield, Keith E

2010-11-01

The unpredictable nature of sickle cell disease (SCD) and its social and environmental consequences can produce an unhealthy and almost exclusive focus on physical functioning. At the upper range of this focus on health concerns is somatization. In the current study, using 156 adult patients (55.13% female, 86) with SCD, mean age 35.59 +/- 12.73, we explored the relationship of somatization to pain. We found somatization to be predictive of pain severity and current pain intensity as well as a range of averaged indices of pain over time (p < .0001). We further found somatization to be predictive of a range of negative psychological experiences to include depression, anxiety, and hostility (p < .0001). We interpret these data to suggest that patients with SCD who have a propensity to focus exclusively on their health or are more sensitive to minor changes in their health status (somatization) may also be more likely to report greater concerns about their health and higher ratings of pain.

Double-blind crossover study of branched-chain amino acid therapy in patients with spinocerebellar degeneration.

PubMed

Mori, Masatada; Adachi, Yoshiki; Mori, Nozomi; Kurihara, Saiko; Kashiwaya, Yoshihiro; Kusumi, Masayoshi; Takeshima, Takao; Nakashima, Kenji

2002-03-30

To determine whether treatment with branched-chain amino acids (BCAA) can improve the condition of patients with ataxia, a double-blind crossover study of BCAA therapy was performed in 16 patients with spinocerebellar degeneration (SCD). The patients were treated with BCAA in oral doses of 1.5, 3.0, or 6.0 g or with placebo daily for 4 weeks in each study phase. The order of treatment phases (placebo or BCAA) was assigned randomly. An International Cooperative Ataxia Rating Scale (ICARS) was used to quantify the severity of symptoms of SCD. The mean ICARS score improved significantly with BCAA treatment compared with the mean pretreatment score (p<0.01). In addition, the improvement in the mean global ICARS score was significant in the middle-dose group compared with that in the placebo group (p<0.02). The estimated improvement in kinetic functions compared with pretreatment (p<0.01) was significant after treatment with BCAA, 1.5 and 3.0 g. All of the responders manifested predominantly cerebellar symptoms, especially those with spinocerebellar ataxia type 6 (SCA6). Thus, treatment with BCAA may be effective in patients with the cerebellar form of SCD.

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

PubMed Central

Astarita, Giuseppe; Jung, Kwang-Mook; Vasilevko, Vitaly; DiPatrizio, Nicholas V.; Martin, Sarah K.; Cribbs, David H.; Head, Elizabeth; Cotman, Carl W.; Piomelli, Daniele

2011-01-01

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. PMID:22046234

Dual kidney transplantation: a case-control comparison with single kidney transplantation from standard and expanded criteria donors.

PubMed

Moore, Phillip S; Farney, Alan C; Sundberg, Aimee K; Rohr, Michael S; Hartmann, Erica L; Iskandar, Samy S; Gautreaux, Michael D; Rogers, Jeffrey; Doares, William; Anderson, Teresa K; Adams, Patricia L; Stratta, Robert J

2007-06-27

The purpose of this study was to perform a case-matched cohort analysis of dual kidney transplantation (DKT) from expanded criteria donors (ECDs) compared to single kidney transplantation (SKT) from concurrent ECDs and standard criteria donors (SCDs, defined as non-ECD). Deceased donor (DD) kidney transplants (KTs) performed at a single center between October 2001 and February 2006 were reviewed retrospectively. If the calculated DD creatinine clearance (CrCl) was <65 mL/min, then the kidneys were transplanted dually into a single patient. In the case of DKT and SKT from ECDs, low risk patients were chosen and informed consent was obtained. Patients in each group were matched for age, gender, race, transplant number, and time of transplant. Of 294 adult DD KTs performed, 16 (5%) were DKTs, which were matched with 16 concurrent SCD and 16 ECD SKT patients. Mean donor age in years (65 DKT vs. 33 SCD vs. 61 ECD; P<0.0001) and mean donor CrCl in ml/min (54 DKT vs. 91 SCD vs. 76 ECD; P=0.002) were different between groups. Patient survival was 100% in the DKT and SCD SKT groups and 94% in the ECD SKT group (mean follow up 23-28 months); graft survival rates in the DKT, SCD, and ECD groups were 81%, 81%, and 94%, respectively (P=NS). Graft function, rejection, and morbidity were similar between groups. DKT using kidneys from marginal ECDs is a viable option to counteract the growing shortage of available organs. Excellent short-term results and renal function can be achieved with older, low nephron mass donors provided that both kidneys are transplanted into a single recipient.

Emergency Department Sickle Cell Assessment of Needs and Strengths (ED-SCANS), a Focus Group and Decision Support Tool Development Project

PubMed Central

Tanabe, Paula; Reddin, Christopher; Thornton, Victoria L.; Todd, Knox H.; Wun, Ted; Lyons, John S.

2010-01-01

Objectives A decision support tool may guide emergency clinicians in recognizing assessment, analgesic and overall management, and health service delivery needs for patients with sickle cell disease (SCD) in the emergency department (ED). We aimed to identify data and process elements important in making decisions regarding evaluation and management of adult patients in the ED with painful episodes of sickle cell disease. Methods Qualitative methods using a series of focus groups and grounded theory were used. Eligible participants included adult clients with SCD, and emergency physicians and nurses with a minimum of one year of experience providing care to patients with SCD in the ED. Patients were recruited in conjunction with annual SCD meetings, and providers included clinicians who were and were not affiliated with sickle cell centers. Groups were conducted until saturation was reached, and included a total of two patient groups, three physician groups, and two nurse groups. Focus groups were held in New York, Durham, Chicago, New Orleans, and Denver. Clinician participants were asked the following three questions to guide the discussion: 1) what information would be important to know about patients with SCD in the ED setting to effectively care for them and help you identify patient analgesic, treatment, and referral needs? 2) what treatment decisions would you make with this information? and 3) what characteristics would a decision support tool need to have to make it meaningful and useful? Client participants were asked the same questions with re-wording to reflect what they believed providers should know to provide the best care, and what they should do with the information. All focus groups were audio taped and transcribed. The constant comparative method was used to analyze the data. Two coders independently coded participant responses and identified focal themes based on the key questions. An investigator and assistant independently reviewed the

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

PubMed

Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

2016-12-27

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Simple Circumcision Device: Proof-of-Concept for a Single-visit, Adjustable Device to Facilitate Safe Adult Male Circumcision

PubMed Central

Hotaling, James M; Leddy, Laura S; Haider, Mahum A; Mossanen, Matthew; Bailey, Michael R; MacConaghy, Brian; Olson, Francis; Krieger, John N

2014-01-01

Objective To conduct a proof-of-concept study to determine the potential utility of a novel, adjustable single-visit, disposable device to facilitate rapid adult circumcision. Design Prospective pilot trial of a novel surgical device Setting Tertiary care Veterans Administration medical center Patients 5 adult males Interventions Circumcisions performed by junior trainees using an adjustable, single-size surgical-assist device constructed by the University of Washington Applied Physics Laboratory. Main Outcome Measure(s) The attending surgeon and trainees completed standardized forms after each procedure to assess technical problems and ease of use. Follow-up visits were scheduled to evaluate adverse events, post-operative pain, cosmetic outcomes and participant satisfaction at 3, 8, 30 and 90 days post-operatively. Results The average operative time was 16.4 minutes. All cases were performed with local anesthesia and no case required electrocautery or conversion to standard surgery. At the post-operative day 3 visit all subjects were happy with their results and would recommend the procedure to another patient. One participant had a minor wound separation noted at the 30-day visit that resolved during follow-up. There were no wound infections, hematomas or other adverse events. Conclusions This proof-of-study suggests that the Simple Circumcision Device (SCD) may facilitate delivery of safe adult male circumcision services. PMID:24613534

Uromodulin retention in thick ascending limb of Henle's loop affects SCD1 in neighboring proximal tubule: renal transcriptome studies in mouse models of uromodulin-associated kidney disease.

PubMed

Horsch, Marion; Beckers, Johannes; Fuchs, Helmut; Gailus-Durner, Valérie; Hrabě de Angelis, Martin; Rathkolb, Birgit; Wolf, Eckhard; Aigner, Bernhard; Kemter, Elisabeth

2014-01-01

Uromodulin-associated kidney disease (UAKD) is a hereditary progressive renal disease which can lead to renal failure and requires renal replacement therapy. UAKD belongs to the endoplasmic reticulum storage diseases due to maturation defect of mutant uromodulin and its retention in the enlarged endoplasmic reticulum in the cells of the thick ascending limb of Henle's loop (TALH). Dysfunction of TALH represents the key pathogenic mechanism of UAKD causing the clinical symptoms of this disease. However, the molecular alterations underlying UAKD are not well understood. In this study, transcriptome profiling of whole kidneys of two mouse models of UAKD, UmodA227T and UmodC93F, was performed. Genes differentially abundant in UAKD affected kidneys of both Umod mutant lines at different disease stages were identified and verified by RT-qPCR. Additionally, differential protein abundances of SCD1 and ANGPTL7 were validated by immunohistochemistry and Western blot analysis. ANGPTL7 expression was down-regulated in TALH cells of Umod mutant mice which is the site of the mutant uromodulin maturation defect. SCD1 was expressed selectively in the S3 segment of proximal tubule cells, and SCD1 abundance was increased in UAKD affected kidneys. This finding demonstrates that a cross talk between two functionally distinct tubular segments of the kidney, the TALH segment and the S3 segment of proximal tubule, exists.

Intravenous Lidocaine as an Adjuvant for Pain Associated with Sickle Cell Disease.

PubMed

Nguyen, Natalie L; Kome, Anne M; Lowe, Denise K; Coyne, Patrick; Hawks, Kelly G

2015-01-01

The objectives of this study were to evaluate the efficacy and safety of adjuvant intravenous (IV) lidocaine in adults with sickle cell disease (SCD). This was a retrospective review. Adults with SCD receiving at least one IV lidocaine infusion from 2004 to 2014 were included. Patient demographics, lidocaine treatment parameters, pain scores, pain medications, and adverse effects were recorded. Eleven patients were identified, yielding 15 IV lidocaine trials. Clinical improvement in pain scores from pre-lidocaine challenge to 24 hours post-lidocaine challenge, defined by ≥ 20% reduction in pain scores, was achieved in 53.3% (8 of 15) of IV lidocaine challenges. Of the 8 clinically successful trials, the mean reduction in morphine dose equivalents (MDE) from 24 hours pre-lidocaine challenge to 24 hours post-lidocaine challenge was 32.2%. Additionally, clinically successful trials had a mean initial and a maximum dose of 1 mg/kg/h (range: 0.5-2.7 mg/kg/h) and 1.3 mg/kg/h (range: 0.5-1.9 mg/kg/h), respectively. On average, these patients underwent 3 dose titrations (range: 1-8) and received lidocaine infusions for 4.4 days (range: 2-8 days). Two patients experienced disorientation and dizziness. The authors conclude that adjuvant IV lidocaine provided pain relief and a mean reduction in MDE during sickle cell pain crisis. These results provide preliminary insight into the use of IV lidocaine for treating pain in patients with SCD, although prospective studies are needed to determine efficacy, dosing, and tolerability of IV lidocaine in this patient population.

Soluble CD30 levels in recipients undergoing heart transplantation do not predict post-transplant outcome.

PubMed

Ypsilantis, Efthymios; Key, Timothy; Bradley, J Andrew; Morgan, C Helen; Tsui, Stephen; Parameshwar, Jayan; Taylor, Craig J

2009-11-01

The pre-transplant serum level of soluble CD30 (sCD30), a proteolytic derivative of the lymphocyte surface receptor CD30, has been suggested as a biomarker for immunologic risk after organ transplantation. Pre-transplant serum sCD30 levels were determined in 200 consecutive adult heart transplant recipients undertaken at a single center. Transplant outcome (acute rejection in the first 12 months and patient survival up to 5 years post-transplant) was determined. Patients treated with a left ventricular assist device (LVAD) prior to transplantation (n = 28) had higher levels of sCD30 (median 64 U/ml, range 12 to 112 U/ml) than those (n = 172) with no LVAD (median 36 U/ml, range 1 to 158 U/ml, p < 0.0001). Recipients were categorized according to whether sCD30 levels were "low" (lower quartile, <24 U/ml, n = 50), "intermediate" (24 to 58 U/ml, n = 100) or "high" (upper quartile, >58 U/ml, n = 50). Neither acute rejection nor recipient survival differed according to sCD30 level, with values (mean +/- SEM) of 0.30 +/- 0.04, 0.23 +/- 0.03 and 0.30 +/- 0.05 acute rejection episodes per 100 days in the low, intermediate and high groups, respectively, with recipient survival rates at 1 year of 77.7%, 84.9% and 86% and at 5 years of 73.6%, 67.9% and 75.8%, respectively. Pre-transplant serum sCD30 level does not predict acute allograft rejection or recipient survival after heart transplantation, although sCD30 levels are increased by LVAD, possibly as a result of biomaterial-host immune interaction.

ADHD Medications and Risk of Serious Cardiovascular Events In Young and Middle-Aged Adults

PubMed Central

Habel, Laurel A.; Cooper, William O.; Sox, Colin M.; Chan, K. Arnold; Fireman, Bruce H.; Arbogast, Patrick G.; Cheetham, T. Craig; Quinn, Virginia P.; Dublin, Sascha; Boudreau, Denise M.; Andrade, Susan E.; Pawloski, Pamala A.; Raebel, Marsha A.; Smith, David H.; Achacoso, Ninah; Uratsu, Connie; Go, Alan S.; Sidney, Steve; Nguyen-Huynh, Mai N; Ray, Wayne A.; Selby, Joe V.

2012-01-01

Context More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention deficit hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. Objective Examine whether current use of medications used primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. Design Retrospective, population-based cohort study Setting Computerized health records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at one site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants Adults aged 25–64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n=150,359) was matched to two non-users on study site, birth year, sex, and calendar year (total users and non-users=443,198). Main Outcome Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke. Comparison between current or new users and remote users to account for potential healthy user bias. Results During 806,182 person-years of follow-up (median 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14–1.57) for MI, 0.30 (95% CI, 0.20–0.42) for SCD, and 0.56 (95% CI, 0.43–0.72) for stroke. The multivariable adjusted rate ratio (RR) of serious cardiovascular events for current use vs non-use of ADHD medications was 0.83 (95% CI 0.72–0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI 0.63–0.94). The adjusted RR was 1.03 (95% CI, 0.86–1.24) for current use vs remote use, and was 1.02 (95% CI

Adult Patients' Experiences of Nursing Care Dependence.

PubMed

Piredda, Michela; Matarese, Maria; Mastroianni, Chiara; D'Angelo, Daniela; Hammer, Marilyn J; De Marinis, Maria Grazia

2015-09-01

Care dependence can be associated with suffering and humiliation. Nurses' awareness of patients' perception of care dependence is crucial to enable them in helping the dependent persons. This study aimed to describe adult patients' experience of nursing care dependence. A metasynthesis was conducted to integrate qualitative findings from 18 studies published through December 2014 on adult patients' experiences of care dependency. Procedures included the Johanna Briggs Institute approach for data extraction, quality appraisal, and integration of findings. The experience of dependence revealed the concept of the embodied person, particularly in relation to care of the physical body. The relationship between the individual and nurses within the context of care had a major impact for dependent patients. When the care relation was perceived as positive, the experience led to the development of the person in finding new balances in life, but when it was perceived as negative, it increased patient' suffering. Care dependence is manifested mostly as bodily dependence and is consistent with its relational nature. The nurse-patient relationship is important to the dependent patients' experience. A greater understanding of patients' experiences of dependence is crucial to enable nurses in improving care and decreasing patient suffering. © 2015 Sigma Theta Tau International.

Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.

PubMed

Zakhour, Ramia; Hachem, Ray; Alawami, Hussain M; Jiang, Ying; Michael, Majd; Chaftari, Anne-Marie; Raad, Issam

2017-10-01

Central venous catheters (CVCs) are essential to treatment of children with cancer. There are no studies comparing catheter-related bloodstream infections (CRBSIs) in pediatric cancer patients to those in adults, although current guidelines for management of CRBSI do not give separate guidelines for the pediatric population. In this study, we compared CRBSIs in both the pediatric and adult cancer population. We retrospectively reviewed the electronic medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD Anderson Cancer Center between September 2005 and March 2014. We evaluated 248 patients with CRBSI. There was a significant difference in etiology of CRBSI between pediatric and adult patients (P = 0.002), with the former having less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10 vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs. 74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult patients. Peripheral blood cultures were available in only 43% of pediatric cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P < 0.0001). We found higher rates of Gram-negative organisms in adults and higher rates of polymicrobial in children. Because of the low rates of peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could be challenging in pediatrics. A modified CRBSI definition relying more on clinical criteria may be warranted. © 2017 Wiley Periodicals, Inc.

Outcomes of Inpatients With and Without Sickle Cell Disease After High-Volume Surgical Procedures

PubMed Central

Dinan, Michaela A.; Chou, Chia-Hung; Hammill, Bradley G.; Graham, Felicia L.; Schulman, Kevin A.; Telen, Marilyn J.; Reed, Shelby D.

2009-01-01

In this study, we examined differences in inpatient costs, length of stay, and in-hospital mortality between hospitalizations for patients with and without sickle cell disease (SCD) undergoing high-volume surgical procedures. We used Clinical Classification Software (CCS) codes to identify discharges in the 2002–2005 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project for patients who had undergone either cholecystectomy or hip replacement. We limited the non-SCD cohort to hospitals where patients with SCD had undergone the same procedure. We compared inpatient outcomes using summary statistics and generalized linear regression analysis to adjust for patient, hospital, and procedural characteristics. Overall, the median age of surgical patients with SCD was more than 3 decades less than the median age of patients without SCD undergoing the same procedure. In recognition of the age disparity, we limited the analyses to patients aged 18 to 64 years. Nonetheless, patients with SCD undergoing cholecystectomy or hip replacement were 12.1 and 14.4 years younger, had inpatient stays that were 73% and 82% longer, and incurred costs that were 46% and 40% higher per discharge than patients without SCD, respectively. Inpatient mortality for these procedures was low, approximately 0.6% for cholecystectomy and 0.2% for hip replacement, and did not differ significantly between patients with and without SCD. Multivariable regression analyses revealed that higher inpatient costs among patients with SCD were primarily attributable to longer hospital stays. Patients with SCD who underwent cholecystectomy or hip replacement required more health care resources than patients without SCD. PMID:19787790

Neuropsychological Assessment of Adult Patients with Shunted Hydrocephalus

PubMed Central

Bakar, Emel Erdogan

2010-01-01

Objective This study is planned to determine the neurocognitive difficulties of hydrocephalic adults. Methods The research group contained healthy adults (control group, n : 15), and hydrocephalic adults (n : 15). Hydrocephalic group consisted of patients with idiopathic aquaduct stenosis and post-meningitis hydrocephalus. All patients were followed with shunted hydrocephalus and not gone to shunt revision during last two years. They were chosen from either asymptomatic or had only minor symptoms without motor and sensorineural deficit. A neuropsychological test battery (Raven Standart Progressive Matrices, Bender-Gestalt Test, Cancellation Test, Clock Drawing Test, Facial Recognition Test, Line Orientation Test, Serial Digit Learning Test, Stroop Color Word Interference Test-TBAG Form, Verbal Fluency Test, Verbal Fluency Test, Visual-Aural Digit Span Test-B) was applied to all groups. Results Neuropsychological assessment of hydrocephalic patients demonstrated that they had poor performance on visual, semantic and working memory, visuoconstructive and frontal functions, reading, attention, motor coordination and executive function of parietal lobe which related with complex and perseverative behaviour. Eventually, these patients had significant impairment on the neurocognitive functions of their frontal, parietal and temporal lobes. On the other hand, the statistical analyses performed on demographic data showed that the aetiology of the hydrocephalus, age, sex and localization of the shunt (frontal or posterior parietal) did not affect the test results. Conclusion This prospective study showed that adult patients with hydrocephalus have serious neuropsychological problems which might be directly caused by the hydrocephalus; and these problems may cause serious adaptive difficulties in their social, cultural, behavioral and academic life. PMID:20379471

The Adult Diabetic Patient: An Education Challenge

DTIC Science & Technology

1993-05-01

finding that he/she, too, must care for sicker patients. To better prepare these patients for life after discharge, patient education must be initiated as...admitted, patient education often begins at the physicians’ office. This paper explores diabetes mellitus in relation to concepts of self-care and adult...betting foj.L eduuation and iio.w, wore ofteni, patient education and follow-up sercvices- a:leL beiny p~rovided on ani outpatient bcdtsis" (p. 36) . Thet

Existence of a soluble form of CD50 (intercellular adhesion molecule-3) produced upon human lymphocyte activation. Present in normal human serum and levels are increased in the serum of systemic lupus erythematosus patients.

PubMed

Pino-Otín, M R; Viñas, O; de la Fuente, M A; Juan, M; Font, J; Torradeflot, M; Pallarés, L; Lozano, F; Alberola-Ila, J; Martorell, J

1995-03-15

CD50 (ICAM-3) is a leukocyte differentiation Ag expressed almost exclusively on hemopoietic cells, with a key role in the first steps of immune response. To develop a specific sandwich ELISA to detect a soluble CD50 form (sCD50), two different mAbs (140-11 and 101-1D2) recognizing non-overlapping epitopes were used. sCD50 was detected in the supernatant of stimulated PBMCs, with the highest levels after CD3 triggering. Simultaneously, the CD50 surface expression diminished during the first 24 h. sCD50 isolated from culture supernatant and analyzed by immunoblotting showed an apparent m.w. of 95 kDa, slightly smaller than the membrane form. These data, together with Northern blot kinetics analysis, suggest that sCD50 is cleaved from cell membrane. Furthermore, we detect sCD50 in normal human sera and higher levels in sera of systemic lupus erythematosus (SLE) patients, especially in those in active phase. The sCD50 levels showed a positive correlation with sCD27 levels (r = 0.4213; p = 0.0026). Detection of sCD50, both after in vitro CD3 triggering of PBMCs and increased in SLE sera, suggests that sCD50 could be used as a marker of lymphocyte stimulation.

Facilitating pediatric patient-provider communications using wireless technology in children and adolescents with sickle cell disease.

PubMed

Jacob, Eufemia; Pavlish, Carol; Duran, Joana; Stinson, Jennifer; Lewis, Mary Ann; Zeltzer, Lonnie

2013-01-01

Use of wireless devices has the potential to transform delivery of primary care services for persons with sickle cell disease (SCD). The study examined text message communications between patients and an advanced practice registered nurse (APRN) and the different primary care activities that emerged with use of wireless technology. Patients (N = 37; mean age 13.9 ± 1.8 years; 45.9% male and 54.1% female) engaged in intermittent text conversations with the APRN as part of the Wireless Pain Intervention Program. Content analyses were used to analyze the content of text message exchanges between patients and the APRN. The primary care needs that emerged were related to pain and symptom management and sickle cell crisis prevention. Two primary care categories (collaborating and coaching), four primary care subcategories (screening, referring, informing, and supporting), and 16 primary care activities were evident in text conversations. The use of wireless technology may facilitate screening, prompt management of pain and symptoms, prevention or reduction of SCD-related complications, more efficient referral for treatments, timely patient education, and psychosocial support in children and adolescents with SCD. Copyright © 2013 National Association of Pediatric Nurse Practitioners. Published by Mosby, Inc. All rights reserved.

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

PubMed

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.

Spine Surgery Outcomes in Elderly Patients Versus General Adult Patients in the United States: A MarketScan Analysis.

PubMed

Lagman, Carlito; Ugiliweneza, Beatrice; Boakye, Maxwell; Drazin, Doniel

2017-07-01

To compare spine surgery outcomes in elderly patients (80-103 years old) versus general adult patients (18-79 years-old) in the United States. Truven Health Analytics MarketScan Research Databases (2000-2012) were queried. Patients with a diagnosis of degenerative disease of the spine without concurrent spinal stenosis, spinal stenosis without concurrent degenerative disease, or degenerative disease with concurrent spinal stenosis and who had undergone decompression without fusion, fusion without decompression, or decompression with fusion procedures were included. Indirect outcome measures included length of stay, in-hospital mortality, in-hospital and 30-day complications, and discharge disposition. Patients (N = 155,720) were divided into elderly (n = 10,232; 6.57%) and general adult (n = 145,488; 93.4%) populations. Mean length of stay was longer in elderly patients versus general adult patients (3.62 days vs. 3.11 days; P < 0.0001). In-hospital mortality was more common in elderly patients versus general adult patients (0.31% vs. 0.06%; P < 0.0001). In-hospital and 30-day complications were more common in elderly patients versus general adult patients (11.3% vs. 7.15% and 17.8% vs. 12.6%; P < 0.0001). Nonroutine discharge was more common in elderly patients versus general adult patients (33.7% vs. 16.2%; P < 0.0001). Our results revealed significantly longer hospital stays, more in-hospital mortalities, and more in-hospital and 30-day complications after decompression without fusion, fusion without decompression, or decompression with fusion procedures in elderly patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Pre-adult versus adult onset major depressive disorder in a naturalistic patient sample: the Leiden Routine Outcome Monitoring Study.

PubMed

van Noorden, M S; Minkenberg, S E; Giltay, E J; den Hollander-Gijsman, M E; van Rood, Y R; van der Wee, N J; Zitman, F G

2011-07-01

Pre-adult onset of major depressive disorder (MDD) may predict a more severe phenotype of depression. As data from naturalistic psychiatric specialty care settings are scarce, we examined phenotypic differences between pre-adult and adult onset MDD in a large sample of consecutive out-patients. Altogether, 1552 out-patients, mean age 39.2 ± 11.6 years, were diagnosed with current MDD on the Mini-International Neuropsychiatric Interview Plus diagnostic interview as part of the usual diagnostic procedure. A total of 1105 patients (71.2%) had complete data on all variables of interest. Pre-adult onset of MDD was defined as having experienced the signs and symptoms of a first major depressive episode before the age of 18 years. Patients were stratified according to the age at interview (20-40/40-65 years). Correlates of pre-adult onset were analysed using logistic regression models adjusted for age, age squared and gender. Univariate analyses showed that pre-adult onset of MDD had a distinct set of demographic (e.g. less frequently living alone) and clinical correlates (more co-morbid DSM-IV - Text Revision diagnoses, more social phobia, more suicidality). In the multivariate model, we found an independent association only for a history of suicide attempts [odds ratio (OR) 3.15, 95% confidence intervals (CI) 1.97-5.05] and current suicidal thoughts (OR 1.81, 95% CI 1.26-2.60) in patients with pre-adult versus adult onset MDD. Pre-adult onset of MDD is associated with more suicidality than adult onset MDD. Age of onset of depression is an easy to ascertain characteristic that may help clinicians in weighing suicide risk.

Ab interno trabeculectomy in the adult patient.

PubMed

SooHoo, Jeffrey R; Seibold, Leonard K; Kahook, Malik Y

2015-01-01

Glaucoma is a potentially blinding disease that affects millions of people worldwide. The mainstay of treatment is lowering of intraocular pressure (IOP) through the use of medications, laser and/or incisional surgery. The trabecular meshwork (TM) is thought to be the site of significant resistance to aqueous outflow in open angle glaucoma. Theoretically, an incision through TM or TM removal should decrease this resistance and lead to a significant reduction in IOP. This approach, commonly referred to as goniotomy or trabeculotomy, has been validated in the pediatric population and has been associated with long-term IOP control. In adults, however, removal of TM tissue has been historically associated with more limited and short-lived success. More recent evidence, reveals that even adult patients may benefit significantly from removal of diseased TM tissue and can lead to a significant reduction in IOP that is long-lasting and safe. In this review, we discuss current evidence and techniques for ab interno trabeculectomy using various devices in the adult patient.

Red cell allo- and autoimmunisation in transfused sickle cell and cancer patients in Kenyatta National Hospital, Nairobi, Kenya

PubMed Central

Mbugua, Amos; Maturi, Peter; Rajab, Jamila; Blasczyk, Rainer; Heuft, Hans-Gert

2015-01-01

Background Currently, no data are available on the prevalence of red blood cell (RBC) antibody formation amongst Kenyan patients with multiple transfusion needs, such as patients with sickle cell disease (SCD) or haematological malignancies (HM) and solid (SM) malignancies. Objectives We determined the prevalence and specificities of RBC alloantibodies and autoantibodies in two patient groups with recurrent transfusion demands at Kenyatta National Hospital, Nairobi, Kenya. Method Between February and August 2014, 300 samples from SCD, HM and SM patients were collected and screened for alloantibodies. Samples from 51 healthy blood donors were screened for irregular antibodies and phenotyped. Results Amongst the 228 patients with viable samples (SCD, n = 137; HM, n = 48; SM, n = 43), the median transfusion frequency was two to three events per group, 38 (16.7%) were RBC immunised and 32 (14.0%) had a positive direct antiglobulin test. We identified specific alloantibodies in six patients (2.6%). Four of these six were SCD patients (2.9%) who had specific RBC alloantibodies (anti-Cw, anti-M, anti-Cob, anti-S); amongst HM patients one had anti-K and one had anti-Lea. RBC autoantibody prevalence was 3.1% (7/228). Amongst the healthy blood donors, the Ror, ccD.ee and R2r, ccD.Ee phenotypes accounted for 82% of the Rhesus phenotypes and all were Kell negative. Conclusion The numbers of transfusions and the rates of RBC alloantibodies are low and the most important RBC alloantibody-inducing blood group antigens are relatively homogeneously distributed in this population. A general change in the Kenyatta National Hospital pre-transfusion test regimen is thus not necessary. The current transfusion practice should be reconsidered if transfusion frequencies increase in the future. PMID:28879098

Meditation and Music Improve Memory and Cognitive Function in Adults with Subjective Cognitive Decline: A Pilot Randomized Controlled Trial.

PubMed

Innes, Kim E; Selfe, Terry Kit; Khalsa, Dharma Singh; Kandati, Sahiti

2017-01-01

While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer's disease. Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured memory and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol Substitution Test (DSST)]. The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK, 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ, DSST, TMT-A/B; p's≤0.04). At 6 months, overall gains were maintained or improved (p's≤0.006), with effect sizes ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment expectancies and did not differ by age, gender, baseline cognition scores, or other factors. Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise for improving outcomes in this population.

Impact of PCA Strategies on Pain Intensity and Functional Assessment Measures in Adults with Sickle Cell Disease during Hospitalized Vaso-Occlusive Episodes

PubMed Central

Dampier, Carlton D.; Wager, Carrie G.; Harrison, Ryan; Hsu, Lewis L.; Minniti, Caterina P.; Smith, Wally R.

2012-01-01

Clinical trials of sickle cell disease (SCD) pain treatment usually observe only small decrements in pain intensity during the course of hospitalization. Sub-optimal analgesic management and inadequate pain assessment methods are possible explanations for these findings. In a search for better methods for assessing inpatient SCD pain in adults, we examined several pain intensity and interference measures in both arms of a randomized controlled trial comparing two different opioid PCA therapies. Based upon longitudinal analysis of pain episodes, we found that scores from daily average Visual Analogue Scales (VAS) and several other measures, especially the Brief Pain Inventory (BPI), were sensitive to change in daily improvements in pain intensity associated with resolution of vaso-occlusive pain. In this preliminary trial, the low demand, high basal infusion (LDHI) strategy demonstrated faster, larger improvements in various measures of pain than the high demand, low basal infusion (HDLI) strategy for opioid PCA dosing, however, verification in larger studies is required. The measures and statistical approaches used in this analysis may facilitate design, reduce sample size, and improve analyses of treatment response in future SCD clinical trials of vaso-occlusive episodes. PMID:22886853

[Bacterial parotitis in an immunocompromised patient in adult ICU].

PubMed

Vassal, O; Bernet, C; Wallet, F; Friggeri, A; Piriou, V

2013-09-01

Bacterial parotitis is a common childhood disease with a favorable outcome. Staphylococcus aureus is the most frequently involved pathogen. Clinical presentation in adult patients can be misleading, Onset occurs in patients with multiple comorbidities, making diagnosis difficult--particularly in ICU. Different pathogens are found in adults with worse outcomes observed. We report here the case of a critically ill patient and discuss diagnosis and management of bacterial parotitis. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

PubMed

Nicholson, Kristina J; McCoy, Kelly L; Witchel, Selma F; Stang, Michael T; Carty, Sally E; Yip, Linwah

2016-10-01

Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary. Copyright © 2016 Elsevier Inc. All rights reserved.

Modifying factors of the health belief model associated with missed clinic appointments among individuals with sickle cell disease.

PubMed

Cronin, Robert M; Hankins, Jane S; Byrd, Jeannie; Pernell, Brandi M; Kassim, Adetola; Adams-Graves, Patricia; Thompson, Alexis A; Kalinyak, Karen; DeBaun, Michael R; Treadwell, Marsha

2018-03-29

Outpatient care is critical in the management of chronic diseases, including sickle cell disease (SCD). Risk factors for poor adherence with clinic appointments in SCD are poorly defined. This exploratory study evaluated associations between modifying variables from the Health Belief Model and missed appointments. We surveyed adults with SCD (n = 211) and caregivers of children with SCD (n = 331) between October 2014 and March 2016 in six centres across the U.S. The survey tool utilized the framework of the Health Belief Model, and included: social determinants, psychosocial variables, social support, health literacy and spirituality. A majority of adults (87%) and caregivers of children (65%) reported they missed a clinic appointment. Children (as reported by caregivers) were less likely to miss appointments than adults (OR:0.22; 95% CI:(0.13,0.39)). In adults, financial insecurity (OR:4.49; 95% CI:(1.20, 20.7)), health literacy (OR:4.64; 95% CI:(1.33, 16.15)), and age (OR:0.95; 95% CI:(0.91,0.99)) were significantly associated with missed appointments. In all participants, lower spirituality was associated with missed appointments (OR:1.83; 95%CI:(1.13, 2.94)). The most common reason for missing an appointment was forgetfulness (adults: 31%, children: 26%). A majority thought reminders would help (adults: 83%, children: 71%) using phone calls (adults: 62%, children: 61%) or text messages (adults: 56%, children: 51%). Our findings demonstrate that modifying components of the Health Belief Model, including age, financial security, health literacy, spirituality, and lacking cues to action like reminders, are important in missed appointments and addressing these factors could improve appointment-keeping for adults and children with SCD.

Personality Traits and Common Psychiatric Conditions in Adult Patients with Acne Vulgaris

PubMed Central

Çölgeçen, Emine

2015-01-01

Background We believe that instances of neuroticism and common psychiatric disorders are higher in adults with acne vulgaris than the normal population. Objective Instances of acne in adults have been increasing in frequency in recent years. The aim of this study was to investigate personality traits and common psychiatric conditions in patients with adult acne vulgaris. Methods Patients who visited the dermatology outpatient clinic at Bozok University Medical School with a complaint of acne and who volunteered for this study were included. The Symptom Checklist 90-Revised (SCL 90-R) Global Symptom Index (GSI), somatization, depression, and anxiety subscales and the Eysenck Personality Questionnaire-Revised Short Form (EPQ-RSF) were administered to 40 patients who fulfilled the inclusion criteria before treatment. The results were compared with those of a control group. Results Of the 40 patients included in this study, 34 were female and 6 were male. The GSI and the somatization, depression, and anxiety subscales of the SCL 90-R were evaluated. Patients with adult acne had statistically significant higher scores than the control group on all of these subscales. In addition, patients with adult acne had statistically significantly higher scores on the neuroticism subscale of the EPQ-RSF. Conclusion Our results show that common psychiatric conditions are frequent in adult patients with acne. More importantly, neurotic personality characteristics are observed more frequently in these patients. These findings suggest that acne in adults is a disorder that has both medical and psychosomatic characteristics and requires a multi-disciplinary approach. PMID:25673931

Pitfalls of using administrative data sets to describe clinical outcomes in sickle cell disease.

PubMed

Claster, Susan; Termuhlen, Amanda; Schrager, Sheree M; Wolfson, Julie A; Iverson, Ellen

2013-12-01

Administrative data sets are increasingly being used to describe clinical care in sickle cell disease (SCD). We recently used such an administrative database to look at the frequency of acute chest syndrome (ACS) and the use of transfusion to treat this syndrome in California patients from 2005 to 2010. Our results revealed a surprisingly low rate of transfusion for this life-threatening situation. To validate these results, we compared California OSPHD (Office of Statewide Health Planning and Development) administrative data with medical record review of patients diagnosed with ACS identified by two pediatric and one adult hospital databases during 2009-2010. ACS or a related pulmonary process accounted for one-fifth of the inpatient hospital discharges associated with the diagnosis of SCD between 2005 and 2010. Only 47% of those discharges were associated with a transfusion. However, chart reviews found that hospital databases over-reported visits for ACS. OSHPD underreported transfusions compared to hospital data. The net effect was a markedly higher true rate of transfusion (40.7% vs. 70.2%). These results point out the difficulties in using this administrative data base to describe clinical care for ACS given the variation in clinician recognition of this entity. OSPHD is widely used to inform health care policy in California and contributes to national databases. Our study suggests that using this administrative database to assess clinical care for SCD may lead to inaccurate assumptions about quality of care for SCD patients in California. Future studies on health services in SCD may require a different methodology. © 2013 Wiley Periodicals, Inc.

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

PubMed

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.

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