Survival and mortality among users and non-users of hydroxyurea with sickle cell disease

OBJECTIVE:

to estimate survival, mortality and cause of death among users or not of hydroxyurea with sickle cell disease.

METHOD:

cohort study with retrospective data collection, from 1980 to 2010 of patients receiving inpatient treatment in two Brazilian public hospitals. The survival probability was determined using the Kaplan-Meier estimator, survival calculations (SPSS version 10.0), comparison between survival curves, using the log rank method. The level of significance was p=0.05.

RESULTS:

of 63 patients, 87% had sickle cell anemia, with 39 using hydroxyurea, with a mean time of use of the drug of 20.0±10.0 years and a mean dose of 17.37±5.4 to 20.94±7.2 mg/kg/day, raising the fetal hemoglobin. In the comparison between those using hydroxyurea and those not, the survival curve was greater among the users (p=0.014). A total of 10 deaths occurred, with a mean age of 28.1 years old, and with Acute Respiratory Failure as the main cause.

CONCLUSION:

the survival curve is greater among the users of hydroxyurea. The results indicate the importance of the nurse incorporating therapeutic advances of hydroxyurea in her care actions.     

Possible high frequency of tetrahydrobiopterin deficiency in South Brazil

Summary We report our experience with the deficiency of 6-pyruvoyltetrahydropterin synthase, the most common form of tetrahydrobiopterin deficiency. We investigated 5200 patients suspected of having some inborn error of metabolism in a 10-year period, and detected 30 cases (from 28 sibships) of hyperphenylalaninaemias, HPA. From these, 4 sibships (5 patients) were affected by deficiency of 6-pyruvoyltetrahydropterin synthase. All of them were ethnically mixed, with some European ancestry detected in all. The age of diagnosis ranged from 2 to 9 years, and all were initially referred for investigation by having mental retardation and seizures. All of them showed low urinary biopterin levels and a marked elevation of neopterin. Although we detected only a few cases of HPA (30), 5 cases of 6-pyruvoyltetrahydropterin account for almost 20% of this total. The literature, however, reports a proportion of around 0.5%. As the frequency of classical phenylketonuria in our region is similar to that found in Caucasians (1/12 500), we believe that the frequency of this disease in South Brazil may be higher than expected (of the order of 1/400 000). We speculate that this finding could be related to a genetic drift (or founder effect).     

Maternal hyperphenylalaninaemia as a cause of microcephaly and mental retardation

We attempted to evaluate the role of maternal hyperphenylalaninaemia (HPA) as an isolated cause of mental retardation and microcephaly in children. This transversal study observed the plasma phenylalanine from mothers of 161 children with mental retardation and/or microcephaly of unknown origin. In this sample, we found two women with previously undiagnosed HPA, a frequency (2/161) higher than expected for our general population (1:12 500) ( p < 0.001). We concluded that the plasma phenylalanine levels should be determined during preconceptional evaluation of every woman of reproductive age that already has had a child affected either by mental retardation or microcephaly of unknown cause. It is particularly significant where women currently having their pregnancies have not been screened for phenylketonuria as newborns, as happens in most developing countries.     

Current autologous transfusion practices. Implications for the future

A questionnaire was distributed to 509 AABB institutional members to evaluate current autologous transfusion practices. Results were returned from 47 blood centers, 108 transfusion services and 64 hospital blood banks (response rate 43%). Results indicate that not all eligible patients are allowed to donate due to unnecessarily strict eligibility criteria. Thirty percent of autologous units are not tested for infectious disease markers. Of those units tested and found positive for anti-HIV or HBsAg, 53 and 72% respectively, of the institutions provide the units to the intended recipient. Forty-seven percent of institutions perform an AHG crossmatch for autologous recipients. Sixty five percent of institutions permit "crossing-over" of autologous units for homologous use. Implications of these findings for the development of standards for autologous transfusion programs are discussed.     

Evidence that acute taurine treatment alters extracellular AMP hydrolysis and adenosine deaminase activity in zebrafish brain membranes

Taurine is one of the most abundant free amino acids in excitable tissues. In the brain, extracellular taurine may act as an inhibitory neurotransmitter, neuromodulator, and neuroprotector. Nucleotides are ubiquitous signaling molecules that play crucial roles for brain function. The inactivation of nucleotide-mediated signaling is controlled by ectonucleotidases, which include the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5′-nucleotidase. These enzymes hydrolyze ATP/GTP to adenosine/guanosine, which exert a modulatory role controlling several neurotransmitter systems. The nucleoside adenosine can be inactivated in extracellular or intracellular milieu by adenosine deaminase (ADA). In this report, we tested whether acute taurine treatment at supra-physiological concentrations alters NTPDase, ecto-5′-nucleotidase, and ADA activities in zebrafish brain. Fish were treated with 42, 150, and 400 mg L⁻¹ taurine for 1 h, the brains were dissected and the enzyme assays were performed. Although the NTPDase activities were not altered, 150 and 400 mg L⁻¹ taurine increased AMP hydrolysis (128 and 153%, respectively) in zebrafish brain membranes and significantly decreased ecto-ADA activity (29 and 38%, respectively). In vitro assays demonstrated that taurine did not change AMP hydrolysis, whereas it promoted a significant decrease in ecto-ADA activity at 150 and 400 mg L⁻¹ (24 and 26%, respectively). Altogether, our data provide the first evidence that taurine exposure modulates the ecto-enzymes responsible for controlling extracellular adenosine levels in zebrafish brain. These findings could be relevant to evaluate potential beneficial effects promoted by acute taurine treatment in the central nervous system (CNS) of this species.     

Evaluation of an aspartame loading test for the detection of heterozygotes for classical phenylketonuria

Classical phenylketonuria (PKU) is an inborn error of metabolism of autosomal recessive inheritance characterized by the accumulation of phenylalanine (Phe) in tissues due to Phe-4-hydroxylase deficiency. Several methods have been developed for the detection of PKU heterozygotes based on the determination of plasma Phe and tyrosine (Tyr) levels, on the analysis of the Phe/Tyr and Phe²/Tyr ratios and on the use of discriminant functions. The objective of the present study was to test the value of loading with aspartame (a sweetener consisting of Phe, aspartate and methanol) for the identification of PKU carriers. The study was conducted on 22 obligate heterozygotes and 27 controls. Two blood samples were collected (under fasting conditions and 30 min after the loading) for fluorometric determination of Phe and Tyr. Phe, Phe/Tyr and Phe²/Tyr values were higher in heterozygotes, whereas Tyr was higher in controls in both situations investigated. Linear discriminant function was considered to be the best parameter for differentiation of the individuals in the two groups. Under the conditions employed in the present study, aspartame loading did not show any advantages in discriminating between PKU carriers and normal individuals when compared to the same analysis performed under fasting conditions.     

Identification of Potentially Diagnostic Leishmania braziliensis Antigens in Human Cutaneous Leishmaniasis by Immunoblot Analysis

The antibody response in patients with American cutaneous leishmaniasis was analyzed by immunoblotting with soluble and insoluble antigens of Leishmania braziliensis. The recognition of the 27- and/or 30-kDa soluble antigens was considered relevant for the diagnosis of cutaneous leishmaniasis. Immunoblotting was found to be significantly more sensitive and specific than indirect immunofluorescence and enzyme-linked immunosorbent assay.     

Predatory activity of the fungus <Emphasis Type="Italic">Duddingtonia flagrans</Emphasis> in equine strongyle infective larvae on natural pasture in the Southern Region of Brazil

Biological control is an alternative method to reduce the population of parasites through natural predators. A promising option of biological control in the reduction of infective larvae on pasture is the use of nematophagous fungi. In this study, the efficacy of the nematophagous fungus Duddingtonia flagrans in controlling gastrointestinal nematode parasites in field-raised horses was tested. Ten foals with an average age of 12 months were divided in two groups: five males constituted the treated group and five females constituted the control group. Each group was introduced in a field of mixed pasture with approximately 5 ha. The treated group received the fungus D. flagrans at a concentration of 10⁶ chlamydospores per kilogramme of animal body weight daily, mixed with horse food for 5 months. The control group did not receive the fungus. Samples were collected to perform eggs per gramme (EPG) counts weekly. Coproculture and collection of pasture were done monthly for larvae counting. No significant difference was observed in the EPG counting and in the number of larvae recovered from coprocultures, where cyathostomines, Strongylus and Trichostrongylus spp. were found after monthly larvae counting. No significant difference was observed in the EPG counts, and Trichostrongylus sp. was identified. The number of recovered larvae on pasture was significantly lower in the treated group in the last month of treatment, showing a reduction of 73.5% (p < 0.05). As such, the fungus was able to reduce the number of infective larvae in the pasture. Nevertheless, this did not reflect in a decrease of parasitic infection during the 5-month study period.