Biomedical subjects

Oswaldo Castro

Publications and source records attributed to Oswaldo Castro.

27 records · Page 2Linked to original sources

PubMed2003

HCV in sickle cell disease.

The sickle cell gene is common in the U.S. In fact 8% of African Americans are healthy carriers of the sickle cell trait (HbAS). People who are homozygous (HbSS) have severe disease. They have life-long anemia, chronic hemolysis, and also have at times hematological crises, which can worsen the anemia. Many patients require chronic transfusions and as a result, substantial proportions of sickle cell patients are at high risk for infection with blood-borne diseases-such as Hepatitis C Virus infection (HCV). The HCV antibody positivity is directly related to the number of transfusions given, and on average the prevalence rate in transfused patients is more than 10%. It is known that the combination of iron overload and HCV can lead to a more rapidly progressive liver disease. The treatment of HCV in sickle cell patients poses a challenge to clinicians. A novel approach described by some is the pre-treatment of these patients with hydroxyurea to increase the fetal hemoglobin, therefore decreasing the severity of Ribavirin-related hemolysis. Treatment with Peg-interferon alone has not been used to treat HCV in sickle cell patients, but in the setting of controlled clinical trials it would be feasible. This review explores the impact of HCV in sickle cell patients and the possible therapeutic options available to them.

Anemia, Sickle Cell↗

PubMed2003

Hepatitis C virus in sickle cell disease.

PURPOSE: To determine the prevalence of hepatitis C virus antibodies (anti-HCV) in patients with sickle cell disease. PATIENTS AND METHODS: Between 1983 and 2001, 150 patients from the Howard University Hospital Center for Sickle Cell Disease were screened for HCV antibody (52% women, 48% men, mean age 34 years). Frozen serum samples from 56 adult sickle cell patients who had participated in previous surveys (1983-92) of HIV and HTLV-1 serology and who were tested in 1992 for anti-HCV antibody--when commercial ELISA test (Ortho) became available--were included in this paper. Of the 150 patients in the study, 132 had sickle cell anemia genotype (SS), 15 had sickle cell hemoglobin-C disease (SC) and three had sickle beta thalassemia. Clinical charts were reviewed for history of blood transfusion, IV drug abuse, homosexuality, tattooing, iron overload, and alcohol abuse. RESULTS: Antibodies to HCV were detected in 53 patients (35.3%). Of the 55 patients who had frozen serum samples tested in 1992, 32 (58%) were reactive for anti-HCV, while only 21 of the 95 patients (22%) tested after 1992 were positive for HCV antibodies (P<0.001). Thirty-nine of 77 patients (51%) who received more than 10 units of packed red blood cells were positive for HCV antibody, and only 14 of 61 patients (23%) who received less than 10 units of packed red blood cells transfusion were positive for HCV antibodies (P<0.001). None of the 12 patients who never received transfusion were positive for HCV antibody. In the 53 anti-HCV positive patients, the mean alanine amino-transferase (ALT) value was 98- and 81 U/L, respectively, for males and females. These values were normal for the HCV-antibody negative patients. The aspartate amino-transferase (AST) and the total bilirubin were also higher in the anti-HCV positive patients compared to patients in the anti-HCV negative group. Forty-four patients (57.1%) who were transfused more than 10 units developed iron overload defined by a serum ferritin level higher than 1,000 ng/ml. A total of 20 of the patients with iron overload underwent liver biopsies. Seven of these 20 patients (35%) were HCV positive. These patients often had more severe liver disease and higher degree of iron deposition. CONCLUSION: The prevalence of HCV antibody and iron overload is directly related to the number of blood transfusions in patients with sickle cell disease. The prevalence of HCV infection has decreased significantly, since blood donor screening for HCV became available. Chronic HCV infection and iron overload place sickle cell patients at risk for significant liver disease.

Adult↗

PubMed2002

Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival.

Few results on cardiac catheterization have been published for patients with sickle cell disease (SCD) with pulmonary hypertension (PHTN). Their survival once this complication develops is unknown. We analyzed hemodynamic data in 34 adult patients with SCD at right-sided cardiac catheterization and determined the relationship of PHTN to patient survival. In 20 patients with PHTN the average systolic, diastolic, and mean pulmonary artery pressures were 54.3, 25.2, and 36.0 mm Hg, respectively. For 14 patients with SCD without PHTN these values were 30.3, 11.7, and 17.8 mm Hg, respectively. The mean pulmonary capillary wedge pressure in patients with PHTN was higher than that in patients without PHTN (16.0 versus 10.6 mm Hg; P =.0091) even though echocardiography showed normal left ventricular systolic function. Cardiac output was high (8.6 L/min) for both groups of patients. The median postcatheterization follow-up was 23 months for patients with PHTN and 45 months for those without PHTN. Eleven patients (55%) with PHTN died compared to 3 (21%) patients without PHTN (chi(2) = 3.83; P =.0503). The mean pulmonary artery pressure had a significant inverse relationship with survival (Cox proportional hazards modeling). Each increase of 10 mm Hg in mean pulmonary artery pressure was associated with a 1.7-fold increase in the rate (hazards ratio) of death (95% CI = 1.1-2.7; P =.028). The median survival for patients with PHTN was 25.6 months, whereas for patients without PHTN the survival was still over 70% at the end of the 119-month observation period (P =.044, Breslow-Gehan log-rank test). Our findings suggest that PHTN in patients with SCD shortened their survival.

Adult↗

PubMed2002

Hydroxyurea treatment of sickle cell anemia in hospital-based practices.

In a published randomized clinical trial, hydroxyurea (HU) improved clinical outcomes in patients with sickle cell anemia (SCA). The mean treatment duration of that trial was 21 months. Here we attempt to determine whether the benefits associated with HU therapy of SCA have led also to successful patient acceptance of HU treatment in community practices, and whether successful clinical outcomes persist beyond 2 years. This is an observational retrospective chart study of the computerized medical records of 60 men and women with SCA who had HU treatment for at least 3 months and who were treated at teaching hospital subspecialty clinics in Baltimore, Maryland, and Washington, D.C. Thirty had remained on therapy for at least 24 months. Admissions declined in this group by 30% (P = 0.04). Declines were seen also in transfusion requirements (-58%, P = 0.07). In 17 of these 30 patients, at least 48 months of follow-up records were available. Fourteen of these remained on therapy the entire period, with similar and sustained reductions in admissions and transfusions. We conclude that hydroxyurea therapy of SCA applied in community settings leads to declining admissions and transfusion rates in many individuals for 4 years or more.

Adult↗

PubMed2002

Nitric oxide and cyclic GMP levels in sickle cell patients receiving hydroxyurea.

Recent studies suggest that nitric oxide (NO) may partly be responsible for the beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) patients. NO stimulates cyclic guanosine monophosphate (cGMP) production, which mediates vasodilatation. We investigated the association between NO, cGMP and fetal haemoglobin (HbF) levels after HU administration. Our data showed that chronic HU significantly increased NO, cGMP, and HbF levels in SCD. Recently it was shown that HbF production was stimulated by cGMP-dependent protein kinase. Our results suggest that NO stimulates cGMP production, which then activates a protein kinase and increases the production of HbF.

Adult↗

PubMed2002

Predicting the effect of transfusing only phenotype-matched RBCs to patients with sickle cell disease: theoretical and practical implications.

BACKGROUND: Transfusing only phenotype-matched RBCs has been recommended to reduce the incidence of alloimmunization to blood group antigens in patients with sickle cell disease (SCD). STUDY DESIGN AND METHODS: The expected benefit of phenotype matching was determined by identifying which of the existing blood group alloantibodies in patients with SCD who received conventional transfusions would not have been formed if they had received only phenotype-matched RBCs. By use of each patient's alloantibodies as a baseline, it was possible to identify specific alloantibodies that would not have been formed if each of five different phenotype-matching protocols had been used. RESULTS: During a 12-year period, 351 patients received transfusions with 8939 units of ABO- and D-matched RBCs. Of these, 102 patients (29.1%) formed at least one blood group alloantibody. An additional 35 patients with SCD with alloantibodies were identified by reviewing clinical records, yielding a total of 137 alloimmunized patients for inclusion in this study. If all transfusions had been selected by limited phenotype matching (C, c, E, e, and K, as well as for ABO and D), all alloantibodies would have been prevented for more than half (53.3%) of the 137 alloimmunized patients. If all transfusions had been matched for C, c, E, e, K, S, Fya, and Jkb, all antibodies would have been prevented for 70.8 percent of the 137 alloimmunized patients. Approximately 13.6 percent of random white blood donors would be expected to match a limited phenotype-matching protocol, whereas only 0.6 percent would match an extended phenotype-matching protocol. CONCLUSION: Limited phenotype matching would have prevented all alloantibodies in 53.3 percent of the patients who formed alloantibodies. This protocol requires RBCs that are readily available. Extended phenotype matching would have prevented alloimmunization in 70.8 percent of patients who formed alloantibodies. However, this would require phenotypes that are 22.7 times less prevalent among random blood donors and is therefore impractical for a long-term strategy.

ABO Blood-Group System↗

PubMed2002

Arterialization of peripheral venous blood in sickle cell disease.

Arterialization of the venous blood is thought to be indicative of cutaneous shunting, and occurs in patients with sickle cell disease (SCD) during vaso-occlusive crisis (VOC). We performed the present study to quantify the amount of shunting that occurs in sickle cell patients presenting at the Howard University Sickle Cell Center, Washington, D.C., as outpatients and for hospitalizations associated with sickle cell crisis. Peripheral venous blood was drawn anaerobically into heparinized syringes from 9 normal control subjects (NC), 24 outpatients (steady-state group), and 14 inpatients during crisis (VOC group). Spectrophotometric measurements were made for the following species of hemoglobin (Hb): oxy-Hb (O2Hb), reduced Hb (RHb), carboxy-Hb (COHb), and met-Hb (MHb). In addition, fetal hemoglobin (HbF) was measured by high-pressure liquid chromatography (HPLC). The O2Hb saturations of the steady state group were not significantly different than those of the NC group (55 +/- 4% vs. 40 +/- 6%). However, the O2Hb saturations of the VOC group were 73 +/- 3%, and this value was found to be significantly greater than those of both the steady-state and the NC groups (p < 0.05). Reduced hemoglobin saturations were inversely related to the O2Hb values, as expected. Compared to the NC group, the steady-state, and VOC groups had greater dyshemoglobin (COHb and MHb) levels (p < 0.05). These findings suggest that the percentages of venous O2Hb and dyshemoglobins may be increased in sickle cell disease even in the absence of VOC. Therefore, the venous O2Hb saturation may be a useful biochemical marker for the arteriovenous shunting and hemodynamic adaptations associated with sickle cell disease.

Adolescent↗

PubMed2000

Nitric Oxide Metabolites in Sickle Cell Anemia Patients after Oral Administration of Hydroxyurea; Hemoglobinopathy.

The mechanism of action of hydroxyurea (HU) in decreasing the frequency of pain crisis in sickle cell disease (SCD) has not been fully elucidated. In vitro and in vivo studies suggest that nitric oxide (NO), a potent vasodilator, may partly be responsible for the beneficial effect of HU. This study was designed to determine the effect of oral administration of HU on plasma levels of NO metabolites (NO(x) ) in sickle cell patients (SCP). The results indicate that during steady-state plasma levels of NO(x) were significantly higher in HU-treated patients compared to non HU-treated patients or normal controls (p <.05). In five inpatients in mild pain plasma levels of NO(x) increased significantly after 2 h of HU administration (p <.05); however, in three inpatients in persistent pain with significantly lower baseline NO(x) there was a minimal NO(x) response to HU at 2 h (p <.01). These observations indicate that HU administration is associated with the production of NO in some SCP, but that further study of the pharmacodynamics of this effect is necessary.

Journal Article↗

PubMedDate not supplied

Iron overload in Africans and African-Americans and a common mutation in the SCL40A1 (ferroportin 1) gene.

The product of the SLC40A1 gene, ferroportin 1, is a main iron export protein. Pathogenic mutations in ferroportin 1 lead to an autosomal dominant hereditary iron overload syndrome characterized by high serum ferritin concentration, normal transferrin saturation, iron accumulation predominantly in macrophages, and marginal anemia. Iron overload occurs in both the African and the African-American populations, but a possible genetic basis has not been established. We analyzed the ferroportin 1 gene in 19 unrelated patients from southern Africa (N = 15) and the United States (N = 4) presenting with primary iron overload. We found a new c. 744 C-->T (Q248H) mutation in the SLC40A1 gene in 4 of these patients (3 Africans and 1 African-American). Among 22 first degree family members, 10 of whom were Q248H heterozygotes, the mutation was associated with a trend to higher serum ferritin to amino aspartate transferase ratios (means of 14.8 versus 4.3 microg/U; P = 0.1) and lower hemoglobin concentrations (means of 11.8 versus 13.2 g/dL; P = 0.1). The ratio corrects serum ferritin concentration for alcohol-induced hepatocellular damage. We also found heterozygosity for the Q248H mutation in 7 of 51 (14%) southern African community control participants selected because they had a serum ferritin concentration below 400 microg/L and in 5 of 100 (5%) anonymous African-Americans, but we did not find the change in 300 Caucasians with normal iron status and 25 Caucasians with non-HFE iron overload. The hemoglobin concentration was significantly lower in the African community controls with the Q248H mutation than in those without it. We conclude that the Q248H mutation is a common polymorphism in the ferroportin 1 gene in African populations that may be associated with mild anemia and a tendency to iron loading.

Black or African American↗