Markers of severe vaso-occlusive painful episode frequency in children and adolescents with sickle cell anemia.

Objective: To identify factors associated with frequent severe vaso-occlusive pain crises in a contemporary pediatric cohort of patients with sickle cell anemia (SCA) enrolled in a prospective study of pulmonary hypertension and the hypoxic response in sickle cell disease.

Study Design: Clinical and laboratory characteristics of children with SCA who had ≥3 severe pain crises requiring health care in the preceding year were compared with those of subjects with <3 such episodes.

Results: Seventy-five children (20%) reported ≥3 severe pain episodes in the preceding year, and 232 (61%) had none.

A novel immune-related gene, microtubule aggregate protein homologue, is up-regulated during IFN-γ-related immune responses in Japanese flounder, Paralichthys olivaceus.

Delayed-type hypersensitivity (DTH) response mediated by antigen-specific Th1 cells is used as a test to detect exposure to tuberculosis in humans. Japanese flounder (Paralichthys olivaceus) microtubule aggregate protein homologue (PoMTAP) was identified as a gene strongly induced during fish DTH response. In this study, PoMTAP gene was cloned and its expression profile was analyzed.

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

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.

Laboratory and echocardiography markers in sickle cell patients with leg ulcers.

Chronic leg ulcers are a debilitating complication of sickle cell disease, associated with increased morbidity and perhaps mortality that affect 8 to 50% of patients. We evaluated the characteristics of SCD patients with a history of leg ulceration, including hemolytic rate, estimated pulmonary artery systolic pressure, and other parameters in a cohort of 505 adults with SCD. Ninety four subjects (18%) had either active ulcers at enrollment or history of leg ulceration.

Priapism in sickle-cell disease: a hematologist's perspective.

Introduction: Priapism is a familiar problem to hematologists, well known for its association with sickle-cell disease (SCD). It also occurs in a variety of other hematological illnesses, nearly all forms of congenital hemolytic anemia, including other hemoglobinopathies and red blood cell membranopathies and enzymopathies.

Aim: Provide urologists with a comprehensive review of priapism in SCD, with an emphasis on the perspective of a practicing hematologist.

Predictors of osteoclast activity in patients with sickle cell disease.

Background: Bone changes are common in sickle cell disease, but the pathogenesis is not fully understood. Tartrate-resistant acid phosphatase (TRACP) type 5b is produced by bone-resorbing osteoclasts. In other forms of hemolytic anemia, increased iron stores are associated with osteoporosis.

Ancestry of African Americans with sickle cell disease.

The inheritance of genetic disease depends on ancestry that must be considered when interpreting genetic association studies and can provide insights when comparing traits in a population. We compared the genetic profiles of African Americans with sickle cell disease to those of Black Africans and Caucasian populations of European descent and found that they are less genetically admixed than other African Americans and have an ancestry similar to Yorubans, Mandenkas and Bantu.

Hospitalization for pain in patients with sickle cell disease treated with sildenafil for elevated TRV and low exercise capacity.

In adults with sickle cell disease (SCD), an increased tricuspid regurgitation velocity (TRV) by Doppler echocardiography is associated with increased morbidity and mortality. Although sildenafil has been shown to improve exercise capacity in patients with pulmonary arterial hypertension, it has not been evaluated in SCD. We therefore sought to determine whether sildenafil could improve exercise capacity in SCD patients with increased TRV and a low exercise capacity.

Nitric oxide for inhalation in the acute treatment of sickle cell pain crisis: a randomized controlled trial.

Context: Inhaled nitric oxide has shown evidence of efficacy in mouse models of sickle cell disease (SCD), case series of patients with acute chest syndrome, and 2 small placebo-controlled trials for treatment of vaso-occlusive pain crisis (VOC).

Objective: To determine whether inhaled nitric oxide gas reduces the duration of painful crisis in patients with SCD who present to the emergency department or hospital for care.

Design, Setting, And Participants: Prospective, multicenter, double-blind, randomized, placebo-controlled clinical trial for up to 72 hours of inhaled nitric oxide gas vs inhaled nitrogen placebo in 150 participants presenting with VOC of SCD at 11 centers between October 5, 2004, and December 22, 2008.

[Endovascular repair for ruptured thoracic aortic aneurysm and traumatic aortic injury].

In contrast to high mortality of open surgery for thoracic aortic catastrophes including ruptured thoracic aortic aneurysm (RTAA) and traumatic aortic injury (TAI), excellent short-term outcomes of thoracic endovascular aortic repair (TEVAR) have recently been reported. We report our single-center experiences with TEVAR for aortic catastrophes. Thirteen patients with thoracic aortic catastrophes (RTAA in 7 patients, TAI in 6 patients) have received TEVAR from February 2004 to June 2010.

The proteome of sickle cell disease: insights from exploratory proteomic profiling.

The expanding realm of exploratory proteomics has added a unique dimension to the study of the complex pathophysiology involved in sickle cell disease. A review of proteomic studies published on sickle cell erythrocytes and plasma shows trends of upregulation of antioxidant proteins, an increase in cytoskeletal defects, an increase in protein repair and turnover components, a decrease in lipid raft proteins and apolipoprotein dysregulation. Many of these findings are consistent with the pathophysiology of sickle cell disease, including high oxidant burden, resulting in damage to cytoskeletal and other proteins, and erythrocyte rigidity.

Vaccine efficacy of Mycobacterium bovis BCG against Mycobacterium sp. infection in amberjack Seriola dumerili.

Mycobacteriosis, caused by the intracellular parasitism Mycobacterium sp., causes economic damages to aquaculture production in Japan, particularly in seriola fish production. Antibiotics are not effective against Mycobacterium sp.

Elevated tricuspid regurgitation velocity and decline in exercise capacity over 22 months of follow up in children and adolescents with sickle cell anemia.

Background: While in adults with sickle cell disease an elevation of tricuspid regurgitation velocity is associated with increased mortality, the importance of this finding in children has not been established. The role of intravascular hemolysis in the development of this complication is controversial.

Design And Methods: We conducted a prospective, longitudinal, multi-center study of 160 individuals aged 3-20 years with hemoglobin SS, performing baseline and follow-up determinations of clinical markers, six-minute walk distance less than tricuspid regurgitation velocity and E/Etdi ratio by echocardiography.

Increased pulmonary pressures and myocardial wall stress in children with severe malaria.

Background: Chronic intravascular hemolysis leads to nitric oxide (NO) depletion and pulmonary hypertension in sickle cell disease. To test whether this pathophysiology occurs in malaria, we examined in Mali 53 children who were admitted to the hospital with severe malaria (excluding cerebral malaria) and 31 age-matched controls.

Methods: Severity of hemolysis was assessed from plasma levels of free hemoglobin and arginase-1.

Diastolic dysfunction in sickle cell.

In adults with sickle cell disease (SCD), echocardiographic evidence of diastolic dysfunction is an independent risk factor for death that is additive to pulmonary hypertension. In this issue of Blood, Johnson and colleagues describe echocardiography and polysomnography results from 44 children with SCD. Because their echocardiograms were ordered for clinical indications, potentially biasing toward more symptomatic patients, the reported prevalence of increased left ventricular mass should be interpreted with caution.

Pericarditis and pleuritis associated with human parvovirus B19 infection in a systemic lupus erythematosus patient.

Human parvovirus B19 (PVB19) infection sometimes shows systemic lupus erythematosus (SLE)-like symptoms. We present an SLE patient showing pericarditis and pleuritis with a fever and an acute swelling of extremities 2 months after the fist consultation. Initially, a diagnosis of SLE exacerbation was made.

Association of G6PD with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia.

The genetic bases of the highly variable degrees of anaemia and haemolysis in persons with Hb SS are not fully known, but several studies have indicated that G6PD deficiency is not a factor. The G6PD(202A) and G6PD(376G) alleles and alpha-thalassaemia were determined by molecular genetic testing in 261 children and adolescents with Hb SS in a multicentre study. G6PD(202A,376G) (G6PD A-) was defined as hemizygosity for both alleles in males and homozygosity in females.

Segmentation and quantification of pulmonary artery for noninvasive CT assessment of sickle cell secondary pulmonary hypertension.

Purpose: Pulmonary arterial hypertension (PAH) is a progressive vascular disease that results in high mortality and morbidity in sickle cell disease (SCD) patients. PAH diagnosis is invasive via right heart catheterization, but manual measurements of the main pulmonary artery (PA) diameters from computed tomography (CT) have shown promise as noninvasive surrogate marker of PAH. The authors propose a semiautomated computer-assisted diagnostic (CAD) tool to quantify the main PA size from pulmonary CT angiography (CTA).

[A case of hard metal lung disease in a man who worked as an iron grinder].

The patient was a man who had suffered from repeated pneumothoraces since August 2003, when he was 16 years old. A right pneumothorax was observed at age 21 years, in April 2008. At the same time, a dry cough began to appear and diffuse small nodular shadows in both lung fields were found on a chest X-ray film.

NT-proBNP as a marker of cardiopulmonary status in sickle cell anaemia in Africa.

N-terminal (NT) pro-brain natriuretic peptide (proBNP) > or =160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross-sectional study at Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria, we studied 133 hydroxycarbamide-naïve Nigerian sickle cell anaemia patients aged 18-52 years at steady-state and 65 healthy controls. Twenty-six percent of patients versus 5% of controls had NT-proBNP > or =160 ng/l (P = 0.

Apolipoprotein A-I and serum amyloid A plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease.

Background: Acute painful episodes are the clinical hallmark of sickle cell disease and have been linked to morbidity and mortality in the sickle cell population.

Design And Methods: We undertook exploratory proteomic studies on paired plasma samples collected from a cohort of 26 adult sickle cell patients during steady state and on the first day of an acute painful episode. We screened for changes in abundance of specific protein peaks via surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), and confirmed the identify of candidate protein peaks by specific immunoassays.