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Biomedical subjects

Elliott P Vichinsky

Publications and source records attributed to Elliott P Vichinsky.

28 records · Page 2Linked to original sources
PubMed2005

A simple model to assess and improve adherence to iron chelation therapy with deferoxamine in patients with thalassemia.

Adherence to deferoxamine (DFO) is vital for the long-term survival of patients with thalassemia; however, currently no measure exists to quantify adherence directly. In this study, 90 patients with thalassemia major underwent liver iron concentration (LIC) assessment by SQUID biosusceptometer, were asked to rate their adherence to DFO using a Numerical Likert Scale (NLS), and were educated about complications of iron overload. Of 38% (n = 28) of patients who rated themselves as very compliant, 19 had elevated LIC related to inadequate dosing of DFO and nine reported nonadherence in the past. Adherence improved after counseling and LIC decreased by 25% (7-60%) in eight previously noncompliant patients who returned for subsequent LIC over 15 months. In conclusion, the NLS seems to be a simple but reliable tool to assess patients' adherence to DFO. Education and frequent noninvasive LIC assessments can improve adherence and iron burden. Elevated LIC does not necessarily reflect concurrent noncompliance; however, it can be an indication of nonadherence in the past.

Adolescent↗
PubMed2003

Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease?

Pulmonary hypertension is a life-threatening complication of sickle cell disease. L-Arginine is the nitrogen donor for synthesis of nitric oxide, a potent vasodilator that is deficient during times of sickle cell crisis. This deficiency may play a role in pulmonary hypertension. The enzyme arginase hydrolyzes arginine to ornithine and urea, and thus, it may compete with nitric oxide synthase, leading to decreased nitric oxide production. Nitric oxide therapy by inhalation has improved pulmonary hypertension associated with acute chest syndrome in sickle cell disease, and several studies demonstrate therapeutic benefits of arginine therapy for primary and secondary pulmonary hypertension. We sought to determine the effects of arginine therapy on pulmonary hypertension in patients with sickle cell disease. Arginase activity was also determined. Oral arginine produced a 15.2% mean reduction in estimated pulmonary artery systolic pressure (63.9 +/- 13 to 54.2 +/- 12 mm Hg, p = 0.002) after 5 days of therapy in 10 patients. Arginase activity was elevated almost twofold (p = 0.07) in patients with pulmonary hypertension and may limit arginine bioavailability. With limited treatment options and a high mortality rate for patients with sickle cell disease who develop pulmonary hypertension, arginine is a promising new therapy that warrants further investigation.

Administration, Oral↗
PubMed2003

Hydroxyurea and arginine therapy: impact on nitric oxide production in sickle cell disease.

PURPOSE: Recent data suggest that hydroxyurea (HU) increases the production of nitric oxide (NO), a potent vasodilator. NO is normally metabolized from l-Arginine (Arg). However, in vitro and animal experiments suggest that HU is the NO donor itself. In contrast, a recent study indicates that nitric oxide synthase (NOS) may play a role. Since adults with sickle cell disease (SCD) are Arg-deficient, Arg availability may limit the ability of HU to maximally impact NO production if an NOS mechanism is involved. The authors have previously shown that Arg supplementation alone induces a paradoxical decrease in NO metabolite (NO(x)) production. METHODS: The authors studied the effects of HU and Arg supplementation on NO(x) production. HU alone or HU + Arg was administered to patients with SCD at steady state, and sequential levels of Arg, serum NO(x) and exhaled NO were followed over 4 hours. RESULTS: After HU + Arg, all patients demonstrated a significant increase in serum NO(x) production within 2 hours. When the same patients were treated with HU alone (5.1 +/- 2 micromol/L), a mixed response occurred. NO(x) levels increased in four patients and decreased in one patient (-23.3 micromol/L). CONCLUSIONS: While Arg alone does not increase serum NO(x) production in SCD patients at steady state, it does when given together with HU. Hence, co-administration of Arg with HU may augment the NO(x) response in SCD and improve utilization of Arg in patients at steady state.

Adolescent↗
PubMed2002

Longitudinal changes in brain magnetic resonance imaging findings in children with sickle cell disease.

Children with sickle cell anemia (HbSS) are at high risk for neurologically overt cerebral infarcts associated with stroke and neurologically silent cerebral infarcts correlated with neuropsychometric deficit. We used complete magnetic resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19 years, who were enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) to examine silent infarct prevalence, localization, recurrence, and progression. We report a baseline prevalence of 21.8%, marginally higher than previously reported due to improved imaging technologies. Although we observed no overall sex difference in prevalence, most lesions in girls occurred before age 6, whereas boys remained at risk until age 10. Silent infarcts were significantly smaller and less likely to be found in the frontal or parietal cortex than were infarcts associated with stroke. Children with silent infarct had an increased incidence of new stroke (1.03/100 patient-years) and new or more extensive silent infarct (7.06/100 patient-years) relative to stroke incidence among all children in our cohort (0.54/100 patient-years). Both events were substantially less frequent than the risk of stroke recurrence among children not provided chronic transfusion therapy. Although chronic transfusion is known to decrease occurrence of new silent infarcts and strokes in children with elevated cerebral arterial blood flow velocity, further study is required to determine its risk-benefit ratio in children with silent infarct and normal velocities. Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities.

Adolescent↗
PubMed2002

Diseases of iron metabolism.

Diseases of iron metabolism are likely to be both more frequent than expected, and exhibit a wider range of clinic severity and effects. Some present without evidence of anemia. Unexplained diseases of end organs that are affected by iron (liver, heart, pancreas, kidney, adrenals, and cerebellum) should have an iron metabolism disorder considered. Review of the blood indices and serum iron and ferritin markers may alert the clinician to most disorders. Further research is likely to define the scope and approach to clinical diagnosis of the diseases of iron metabolism.

Humans↗
PubMed2002

Effect of hydroxyurea on growth in children with sickle cell anemia: results of the HUG-KIDS Study.

OBJECTIVES: Although hydroxyurea is effective in treating adults with sickle-cell anemia (SCA), there is concern that it may adversely affect growth in children. We report the growth characteristics of patients in the Phase I-II pediatric hydroxyurea trial (HUG-KIDS) before and during treatment at the maximum tolerated dose for one year. STUDY DESIGN: Children and adolescents with SCA (n = 68), aged 5 to 16 years at baseline, reached the maximum tolerated dose and had serial height, weight, and Tanner stage measurements. Data from the Cooperative Study of Sickle Cell Disease (CSSCD) were used for comparison. Mixed-effects models were used to compare serial measurements as a function of age and group. RESULTS: In girls, there were no significant differences in height or weight among the pretreatment, on-treatment, and CSSCD groups. Compared with the CSSCD group, HUG-KIDS boys were heavier starting at age 9 years, and pretreatment HUG-KIDS boys were taller starting at age 7 years. The Tanner stage transitions took place at appropriate ages. CONCLUSIONS: Hydroxyurea treatment had no adverse effect on height or weight gain or pubertal development in school-aged children with SCA.

Adolescent↗
PubMedDate not supplied

Liver ferritin subunit ratios in neonatal hemochromatosis.

Neonatal hemochromatosis is an enigmatic disease. Little is known about iron metabolism in this disease, including the tissue concentration of ferritin or its H and L subunit ratio. The authors report the tissue iron, ferritin, and ferritin subunit content of a child who died at 5 weeks of neonatal hemochromatosis. The child was born at 29 weeks gestation to a mother with lupus, sickle cell trait, and gestational diabetes. The child's severe liver dysfunction led to the clinical diagnosis of neonatal hemochromatosis at 1 week of age. Despite aggressive support, including red cell transfusions and chelation, the child died of an intracranial hemorrhage. Autopsy showed liver fibrosis and iron staining characteristic of neonatal hemochromatosis. Autopsy liver tissue was compared to age-matched control tissue. Soluble protein was analyzed by the Bradford method. Soluble iron (over 90% of total iron) was analyzed by the o-phenanthroline complex. Tissue ferritin and human ferritin controls (Calzyme) were analyzed by Western blotting after SDS-PAGE, identified with sheep anti-human ferritin antibodies (The BindingSite) secondary antibody-fluorescence for detection, and quantified using the Molecular Dynamics Storm 840 phosphorimager and ImageQuant software. Protein, iron, and total ferritin were similar in the normal and neonatal hemochromatosis liver tissues. Ferritin subunits, however, showed an increased H/L-subunit ratio compared to an age-matched control. This first report of a marked increase in the ferritin H/L-subunit ratio may point to an underlying mechanism of disease in this enigmatic disorder.

Biopsy↗