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1.
Blood ; 119(16): 3684-90, 2012 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-22096242

RESUMO

The most common form of neurologic injury in sickle cell anemia (SCA) is silent cerebral infarction (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial, we sought to identify risk factors associated with SCI. In this cross-sectional study, we evaluated the clinical history and baseline laboratory values and performed magnetic resonance imaging of the brain in participants with SCA (HbSS or HbSß° thalassemia) between the ages of 5 and 15 years with no history of overt stroke or seizures. Neuroradiology and neurology committees adjudicated the presence of SCI. SCIs were diagnosed in 30.8% (251 of 814) participants who completed all evaluations and had valid data on all prespecified demographic and clinical covariates. The mean age of the participants was 9.1 years, with 413 males (50.7%). In a multivariable logistic regression analysis, lower baseline hemoglobin concentration (P < .001), higher baseline systolic blood pressure (P = .018), and male sex (P = .030) were statistically significantly associated with an increased risk of an SCI. Hemoglobin concentration and systolic blood pressure are risk factors for SCI in children with SCA and may be therapeutic targets for decreasing the risk of SCI. This study is registered at www.clinicaltrials.gov as #NCT00072761.


Assuntos
Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Pressão Sanguínea , Transfusão de Sangue , Infarto Cerebral/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Anemia Falciforme/sangue , Doenças Assintomáticas/epidemiologia , Infarto Cerebral/sangue , Infarto Cerebral/patologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Hemoglobina Falciforme/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Análise Multivariada , Fatores de Risco , Distribuição por Sexo , Talassemia beta/sangue
2.
Carbohydr Res ; 542: 109202, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38954850

RESUMO

Alternansucrase, a glucosyltransferase, is currently used to produce slowly digestible alternan oligosaccharides or maltooligosaccharides from sucrose. These oligosaccharides are popular for food fortification to lower postprandial glucose levels. This study aimed to explore the enzymatic reaction of alternansucrase in simulated in vitro gastric reaction conditions. Under the studied conditions, SucroSEB (a model enzyme for alternansucrase) hydrolyzed the sucrose and transglycosylated the glucose to produce glucans, both in the absence and presence of acceptors. The preference of the acceptor was maltose˃ raffinose˃ lactose. The rate of sucrose hydrolysis was significantly higher in the presence of maltose (p = 0.024). The glucans formed during the reaction included oligomers (DP 3-10) and polymers (DP ≥ 11), both of which increased over time. These glucans contained α-1,3 and α-1,6 glycosidic linkages, confirmed by 1H and 13C NMR. They were slowly and partially digestible in the presence of rat intestinal extract in contrast to the complete and rapid digestion of starch. The glucans formed after a longer gastric reaction time exhibited higher dietary fiber potential (19.145 ± 4.77 %; 60 min) compared to those formed during the initial phase (2.765 ± 0.19 %; 15 min). Overall, this study demonstrated the efficacy of SucroSEB in converting sucrose to slowly and partially digestible glucans under simulated in vitro gastric conditions.

3.
Blood ; 117(9): 2614-7, 2011 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-21217080

RESUMO

We evaluated spleen function in 193 children with sickle cell anemia 8 to 18 months of age by (99m)Tc sulfur-colloid liver-spleen scan and correlated results with clinical and laboratory parameters, including 2 splenic biomarkers: pitted cell counts (PIT) and quantitative Howell-Jolly bodies (HJB) enumerated by flow cytometry. Loss of splenic function began before 12 months of age in 86% of infants in association with lower total or fetal hemoglobin and higher white blood cell or reticulocyte counts, reinforcing the need for early diagnosis and diligent preventive care. PIT and HJB correlated well with each other and liver-spleen scan results. Previously described biomarker threshold values did define patients with abnormal splenic function, but our data suggest that normal spleen function is better predicted by PIT of ≤1.2% or HJB ≤55/10(6) red blood cells and absent function by PIT ≥4.5% or HJB ≥665/10(6). HJB is methodologically advantageous compared with PIT, but both are valid biomarkers of splenic function. This trial was registered at www.clinicaltrials.gov as #NCT00006400.


Assuntos
Anemia Falciforme/fisiopatologia , Baço/fisiopatologia , Anemia Falciforme/sangue , Anemia Falciforme/patologia , Biomarcadores/metabolismo , Contagem de Eritrócitos , Inclusões Eritrocíticas/patologia , Feminino , Humanos , Lactente , Fígado/metabolismo , Fígado/patologia , Masculino , Baço/patologia
4.
Br J Haematol ; 157(5): 627-36, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22463614

RESUMO

Acute chest syndrome (ACS) is defined as fever, respiratory symptoms and a new pulmonary infiltrate in an individual with sickle cell disease (SCD). Nearly half of ACS episodes occur in SCD patients already hospitalized, potentially permitting pre-emptive therapy in high-risk patients. Simple transfusion of red blood cells may abort ACS if given to patients hospitalized for pain who develop fever and elevated levels of secretory phospholipase A2 (sPLA2). In a feasibility study (PROACTIVE; ClinicalTrials.gov NCT00951808), patients hospitalized for pain who developed fever and elevated sPLA2 were eligible for randomization to transfusion or observation; all others were enrolled in an observational arm. Of 237 enrolled, only 10 were randomized; one of the four to receive transfusion had delayed treatment. Of 233 subjects receiving standard care, 22 developed ACS. A threshold level of sPLA2 ≥ 48 ng/ml gave optimal sensitivity (73%), specificity (71%) and accuracy (71%), but a positive predictive value of only 24%. The predictive value of sPLA2 was improved in adults and patients with chest or back pain, lower haemoglobin concentration and higher white blood cell counts, and in those receiving less than two-thirds maintenance fluids. The hurdles identified in PROACTIVE should facilitate design of a larger, definitive, phase 3 randomized controlled trial.


Assuntos
Síndrome Torácica Aguda/diagnóstico , Síndrome Torácica Aguda/etiologia , Anemia Falciforme/complicações , Fosfolipases A2 Secretórias/sangue , Síndrome Torácica Aguda/sangue , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Criança , Estudos de Viabilidade , Feminino , Humanos , Masculino , Prognóstico , Adulto Jovem
5.
Lancet ; 377(9778): 1663-72, 2011 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-21571150

RESUMO

BACKGROUND: Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. METHODS: This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sß(0)thalassaemia, were aged 9-18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on (99)Tc spleen scan) and renal function (glomerular filtration rate by (99m)Tc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2-4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. FINDINGS: 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m(2), p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. INTERPRETATION: On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. FUNDING: The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/fisiopatologia , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Síndrome Torácica Aguda/etiologia , Síndrome Torácica Aguda/prevenção & controle , Anemia Falciforme/complicações , Anemia Falciforme/metabolismo , Anemia Falciforme/patologia , Antidrepanocíticos/efeitos adversos , Biomarcadores/sangue , Contagem de Células Sanguíneas , Desenvolvimento Infantil , Feminino , Taxa de Filtração Glomerular , Hemoglobinas/metabolismo , Humanos , Hidroxiureia/efeitos adversos , Lactente , Masculino , Concentração Osmolar , Dor/etiologia , Dor/prevenção & controle , Baço/patologia , Baço/fisiopatologia , Pentetato de Tecnécio Tc 99m/metabolismo , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana , Estados Unidos , Urina/química
6.
N Engl J Med ; 360(16): 1618-27, 2009 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-19369668

RESUMO

BACKGROUND: Black patients with hemophilia A (factor VIII deficiency) are twice as likely as white patients to produce inhibitors against factor VIII proteins given as replacement therapy. There are six wild-type factor VIII proteins, designated H1 through H6, but only two (H1 and H2) match the recombinant factor VIII products used clinically. H1 and H2 are found in all racial groups and are the only factor VIII proteins found in the white population to date. H3, H4, and H5 have been found only in blacks. We hypothesized that mismatched factor VIII transfusions contribute to the high incidence of inhibitors among black patients. METHODS: We sequenced the factor VIII gene (F8) in black patients with hemophilia A to identify causative mutations and the background haplotypes on which they reside. Results from previous Bethesda assays and information on the baseline severity of hemophilia, age at enrollment, and biologic relationships among study patients were obtained from review of the patients' medical charts. We used multivariable logistic regression to control for these potential confounders while testing for associations between F8 haplotype and the development of inhibitors. RESULTS: Of the 78 black patients with hemophilia enrolled, 24% had an H3 or H4 background haplotype. The prevalence of inhibitors was higher among patients with either of these haplotypes than among patients with haplotype H1 or H2 (odds ratio, 3.6; 95% confidence interval, 1.1 to 12.3; P=0.04), despite a similar spectrum of hemophilic mutations and degree of severity of illness in these two subgroups. CONCLUSIONS: These preliminary results suggest that mismatched factor VIII replacement therapy may be a risk factor for the development of anti-factor VIII alloantibodies.


Assuntos
População Negra/genética , Inibidores dos Fatores de Coagulação Sanguínea/imunologia , Fator VIII/genética , Fator VIII/imunologia , Hemofilia A/etnologia , Hemofilia A/imunologia , Adolescente , Adulto , Sequência de Aminoácidos , Anticorpos , Inibidores dos Fatores de Coagulação Sanguínea/genética , Criança , Pré-Escolar , Fator VIII/uso terapêutico , Haplótipos , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Isoanticorpos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem
7.
Pediatr Blood Cancer ; 59(4): 675-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22190441

RESUMO

BACKGROUND: Clinical complications of sickle cell anemia begin in infancy. BABY HUG (ClinicalTrials.gov, NCT00006400) was a NHLBI-NICHD supported randomized phase III placebo-controlled trial of hydroxyurea (HU) in infants (recruited at 9-18 months) unselected for clinical severity with sickle cell anemia. This secondary analysis of data from BABY HUG examines the influence of anemia on the incidence of sickle cell related complications, and the impact of hydroxyurea therapy in altering these events by comparing children with lower (<25th percentile) and higher (>75th percentile) hemoglobin concentrations at study entry. PROCEDURE: Infants were categorized by: (1) age-adjusted hemoglobin quartiles as determined by higher (Hi) and lower (Lo) hemoglobin concentrations at study entry (9-12 months old: <8.0 and >10.0 gm/dL; 12-18 months old: <8.1 and >9.9 gm/dL) and (2) treatment arm (hydroxyurea or placebo). Four subgroups were created: placebo (PL) LoHb (n = 25), PL HiHb (n = 27), hydroxyurea (HU) LoHb (n = 21), and HU HiHb (n = 18). The primary and secondary endpoints of BABY HUG were analyzed by subgroup. RESULTS: Infants with lower hemoglobin at baseline were more likely to have a higher incidence of clinical events (acute chest syndrome, pain crisis, fever) as well as higher TCD velocities and lower neuropsychological scores at study exit. Hydroxyurea reduced the incidence of these findings. CONCLUSION: Infants with more severe anemia are at risk for increased clinical events that may be prevented by early initiation of hydroxyurea.


Assuntos
Anemia Falciforme/complicações , Doença Aguda , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/fisiopatologia , Antidrepanocíticos/uso terapêutico , Método Duplo-Cego , Febre/etiologia , Hemoglobinas/análise , Humanos , Hidroxiureia/uso terapêutico , Lactente , Rim/fisiopatologia , Dor/etiologia , Baço/fisiopatologia , Doenças Torácicas/etiologia
8.
Pediatr Blood Cancer ; 59(4): 668-74, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22294512

RESUMO

BACKGROUND: Children with sickle cell anemia (SCA) often develop hyposthenuria and renal hyperfiltration at an early age, possibly contributing to the glomerular injury and renal insufficiency commonly seen later in life. The Phase III randomized double-blinded Clinical Trial of Hydroxyurea in Infants with SCA (BABY HUG) tested the hypothesis that hydroxyurea can prevent kidney dysfunction by reducing hyperfiltration. PROCEDURE: 193 infants with SCA (mean age 13.8 months) received hydroxyurea 20 mg/kg/day or placebo for 24 months. (99m) Tc diethylenetriaminepentaacetic acid (DTPA) clearance, serum creatinine, serum cystatin C, urinalysis, serum and urine osmolality after parent-supervised fluid deprivation, and renal ultrasonography were obtained at baseline and at exit to measure treatment effects on renal function. RESULTS: At exit children treated with hydroxyurea had significantly higher urine osmolality (mean 495 mOsm/kg H(2) O compared to 452 in the placebo group, P = 0.007) and a larger percentage of subjects taking hydroxyurea achieved urine osmolality >500 mOsm/kg H(2) O. Moreover, children treated with hydroxyurea had smaller renal volumes (P = 0.007). DTPA-derived glomerular filtration rate (GFR) was not significantly different between the two treatment groups, but was significantly higher than published norms. GFR estimated by the Chronic Kidney Disease in Children (CKiD) Schwartz formula was the best non-invasive method to estimate GFR in these children, as it was the closest to the DTPA-derived GFR. CONCLUSION: Treatment with hydroxyurea for 24 months did not influence GFR in young children with SCA. However, hydroxyurea was associated with better urine concentrating ability and less renal enlargement, suggesting some benefit to renal function.


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Rim/fisiopatologia , Anemia Falciforme/complicações , Anemia Falciforme/fisiopatologia , Anemia Falciforme/urina , Creatinina/sangue , Cistatina C/sangue , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Lactente , Rim/diagnóstico por imagem , Falência Renal Crônica/etiologia , Falência Renal Crônica/prevenção & controle , Masculino , Concentração Osmolar , Cintilografia , Compostos Radiofarmacêuticos , Pentetato de Tecnécio Tc 99m , Ultrassonografia
9.
Blood ; 114(21): 4632-8, 2009 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-19721013

RESUMO

Chronic blood transfusion is increasingly indicated in patients with sickle cell disease. Measuring resulting iron overload remains a challenge. Children without viral hepatitis enrolled in 2 trials for stroke prevention were examined for iron overload (STOP and STOP2; n = 271). Most received desferrioxamine chelation. Serum ferritin (SF) changes appeared nonlinear compared with prechelation estimated transfusion iron load (TIL) or with liver iron concentrations (LICs). Averaged correlation coefficient between SF and TIL (patients/observations, 26 of 164) was r = 0.70; between SF and LIC (patients/observations, 33 of 47) was r = 0.55. In mixed models, SF was associated with LIC (P = .006), alanine transaminase (P = .025), and weight (P = .026). Most patients with SF between 750 and 1500 ng/mL had a TIL between 25 and 100 mg/kg (72.8% +/- 5.9%; patients/observations, 24 of 50) or an LIC between 2.5 and 10 mg/g dry liver weight (75% +/- 0%; patients/observations, 8 of 9). Most patients with SF of 3000 ng/mL or greater had a TIL of 100 mg/kg or greater (95.3% +/- 6.7%; patients/observations, 7 of 16) or an LIC of 10 mg/g dry liver weight or greater (87.7% +/- 4.3%; patients/observations, 11 of 18). Although SF changes are nonlinear, levels less than 1500 ng/mL indicated mostly acceptable iron overload; levels of 3000 ng/mL or greater were specific for significant iron overload and were associated with liver injury. However, to determine accurately iron overload in patients with intermediately elevated SF levels, other methods are required. These trials are registered at www.clinicaltrials.gov as #NCT00000592 and #NCT00006182.


Assuntos
Anemia Falciforme/sangue , Ferritinas/sangue , Sobrecarga de Ferro/etiologia , Cirrose Hepática/etiologia , Reação Transfusional , Alanina Transaminase , Anemia Falciforme/complicações , Área Sob a Curva , Criança , Desferroxamina/uso terapêutico , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/sangue , Curva ROC , Sideróforos/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle
10.
Pediatr Blood Cancer ; 57(6): 1011-7, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-21826782

RESUMO

BACKGROUND: Stroke occurs in 5-10% of children with sickle cell anemia (SCA) and has a high (>50%) risk of recurrence without therapy. Chronic monthly erythrocyte transfusions effectively prevent recurrent stroke, but their long-term use is limited by serious side effects, including iron overload. An alternative to transfusion for secondary stroke prevention in SCA is needed, especially one that also improves the management of iron overload. METHODS: Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) is an NHLBI-sponsored Phase III multicenter randomized controlled clinical trial for children with SCA, stroke, and iron overload (NCT00122980). The primary goal of SWiTCH is to compare 30 months of alternative therapy (hydroxyurea and phlebotomy) with standard therapy (transfusions and chelation) for the prevention of secondary stroke and reduction of transfusional iron overload. DISCUSSION: SWiTCH has several distinctive study features including novel methodological and design components: (1) composite primary endpoint including both stroke recurrence rate and iron burden; (2) non-inferiority design with an "acceptable" increased stroke risk; (3) transfusion goals based on current academic community practices; (4) special oversight for the enrollment and randomization process; (5) overlap treatment period within the alternative treatment arm; (6) masking of the overall trial Principal Investigator to treatment results; (7) inclusive independent stroke adjudication process for all suspected new neurological events; and (8) periodic therapeutic phlebotomy program to alleviate iron overload. CONCLUSION: Investigation of alternative treatments in SWiTCH could lead to changes in the management of cerebrovascular disease for selected patients with SCA, stroke, and iron overload.


Assuntos
Anemia Falciforme/terapia , Transfusão de Eritrócitos , Hidroxiureia/uso terapêutico , Sobrecarga de Ferro/terapia , Acidente Vascular Cerebral/terapia , Adolescente , Adulto , Anemia Falciforme/complicações , Terapia por Quelação , Criança , Pré-Escolar , Transfusão de Eritrócitos/efeitos adversos , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto Jovem
11.
Ann Trop Paediatr ; 31(2): 163-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21575323

RESUMO

Intra-abdominal calcification is uncommon in newborns and has several causes of which meconium peritonitis is the most frequent. Three neonates with intra-abdominal calcification as a complication of meconium peritonitis are presented. The types of meconium peritonitis were cystic, meconium pseudocyst and meconium ascites. Two required surgical intervention. Meconium peritonitis should be considered in newborns with intra-abdominal calcification.


Assuntos
Calcinose/diagnóstico , Mecônio/diagnóstico por imagem , Peritonite/complicações , Peritonite/diagnóstico , Adulto , Calcinose/etiologia , Calcinose/patologia , Feminino , Humanos , Recém-Nascido , Masculino , Peritonite/etiologia , Peritonite/patologia , Radiografia Abdominal , Ultrassonografia
12.
J Pediatr ; 156(1): 66-70.e1, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19880138

RESUMO

OBJECTIVES: To examine the feasibility and accuracy of glomerular filtration rate (GFR) measurements in infants with sickle cell anemia (SCA). STUDY DESIGN: The NHLBI/NICHD-sponsored Phase III randomized double-blinded placebo-controlled trial (BABY HUG) tests the hypothesis that hydroxyurea can prevent chronic organ damage in SCA. GFR elevation is a coprimary endpoint, measured quantitatively by technetium 99m-labeled diethylenetriaminepentaacetic acid (DTPA) plasma clearance and estimated by the Schwartz equation with height and creatinine. RESULTS: Baseline DTPA GFR measurement was attempted in 191 infants; 176 of 184 completed studies (96%) were interpretable. Average age (mean +/- 1SD) was 13.7 +/- 2.6 months. Average DTPA GFR was 125.2 +/- 34.4 (range 40.2-300.9, normal 91.5 +/- 17.8 mL/min/1.73m(2)), while Schwartz estimates were higher at 184.4 +/- 55.5 mL/min/1.73m(2). DTPA GFR was correlated with Schwartz GFR (r(2) = 0.0658, P = .0012); also with age, weight, height, and kidney volume (all P < .002); but not with hemoglobin, HbF, white blood cell count, reticulocytes, medical events, or splenic function. CONCLUSIONS: Quantitative GFR measurement is feasible but variable among infants with SCA. Schwartz GFR estimates are not highly correlated with quantitative DTPA GFR values. Baseline GFR measurements suggest that renal dysfunction in SCA, evidenced by glomerular hyperfiltration, begins during infancy.


Assuntos
Anemia Falciforme/fisiopatologia , Rim/fisiopatologia , Baço/fisiopatologia , Creatinina/sangue , Taxa de Filtração Glomerular , Humanos , Lactente , Ácido Pentético/sangue
13.
Pediatr Blood Cancer ; 54(2): 260-4, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19856395

RESUMO

BACKGROUND: Subject retention and adherence are essential to maintain the power and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We designed a study to assess adherence with study medication administration and study visits and to evaluate socioeconomic factors (SES) that may influence these measurements of adherence. These data are important for assessing impact of adherence on BABY HUG trial outcome and defining impact of SES on adherence. METHODS: Each subject's median study medication (MedAd) and mean visit adherence (VAd) were evaluated. We examined associations of adherence with SES of participating families. RESULTS: MedAd data were available on 153 of the 191 subjects who started randomized study medication. MedAd was 101.7% of volume prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were available on 185 of the 191 subjects who started randomized study medication. VAd was 97.3%, with 82.2% of subjects having no missed visits. During dose titration, subjects had on average 12.9% higher medication adherence than subjects who were on a stable dose and had less frequent study visits. MedAd and VAd were not significantly associated with SES. CONCLUSION: Subjects in the BABY HUG trial have had excellent adherence. SES was not associated with adherence, suggesting that SES should not be used as a criterion for enrolment in clinical trials. Additional efforts are needed to maintain medication adherence, particularly when the interval between scheduled visits increases. (ClinicalTrials.gov number, NCT00006400).


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Hidroxiureia/uso terapêutico , Cooperação do Paciente , Pacientes Desistentes do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Humanos , Lactente , Masculino
14.
Pediatr Blood Cancer ; 54(2): 256-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19813252

RESUMO

BACKGROUND: Transcranial Doppler ultrasonography (TCD) is used to predict stroke risk in children with sickle cell anemia (SCA), but has not been adequately studied in children under age 2 years. PROCEDURE: TCD was performed on infants with SCA enrolled in the BABY HUG trial. Subjects were 7-17 months of age (mean 12.6 months). TCD examinations were successfully performed in 94% of subjects (n = 192). RESULTS: No patient had an abnormal TCD as defined in the older child (time averaged maximum mean TAMM velocity > or =200 cm/sec) and only four subjects (2%) had velocities in the conditional range (170-199 cm/sec). TCD velocities were inversely related to hemoglobin (Hb) concentration and directly related to increasing age. CONCLUSION: Determination of whether the TCD values in this very young cohort of infants with SCA can be used to predict stroke risk later in childhood will require analysis of exit TCD's and long-term follow-up, which is ongoing (ClinicalTrials.gov number, NCT00006400).


Assuntos
Anemia Falciforme/complicações , Acidente Vascular Cerebral/prevenção & controle , Ultrassonografia Doppler Transcraniana , Fatores Etários , Circulação Cerebrovascular , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Análise Multivariada , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico por imagem
15.
Pediatr Blood Cancer ; 54(2): 250-5, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19731330

RESUMO

Evidence of the laboratory benefits of hydroxyurea and its clinical efficacy in reducing acute vaso-occlusive events in adults and children with sickle cell anemia has accumulated for more than 15 years. A definitive clinical trial showing that hydroxyurea can also prevent organ damage might support widespread use of the drug at an early age. BABY HUG is a randomized, double-blind placebo-controlled trial to test whether treating young children ages 9-17 months at entry with a liquid preparation of hydroxyurea (20 mg/kg/day for 2 years) can decrease organ damage in the kidneys and spleen by at least 50%. Creation of BABY HUG entailed unique challenges and opportunities. Although protection of brain function might be considered a more compelling endpoint, preservation of spleen and renal function has clinical relevance, and significant treatment effects might be discernable within the mandated sample size of 200. Concerns about unanticipated severe toxicity and burdensome testing and monitoring requirements were addressed in part by an internal Feasibility and Safety Pilot Study, the successful completion of which was required prior to enrolling a larger number of children on the protocol. Concerns over recruitment of potentially vulnerable subjects were allayed by inclusion of a research subject advocate, or ombudsman. Finally, maintenance of blinding of research personnel was aided by inclusion of an unblinded primary endpoint person, charged with transmitting endpoint data and monitoring blood work locally for toxicity (ClinicalTrials.gov number, NCT00006400).


Assuntos
Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Hidroxiureia/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Fatores Etários , Antidrepanocíticos/administração & dosagem , Antidrepanocíticos/efeitos adversos , Método Duplo-Cego , Monitoramento de Medicamentos , Determinação de Ponto Final , Humanos , Hidroxiureia/administração & dosagem , Hidroxiureia/efeitos adversos , Lactente , Projetos Piloto
16.
J Clin Neurosci ; 68: 1-8, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31416731

RESUMO

Molecular aberrations of malignancy are becoming widely recognized as important predictive and prognostic markers for treatment response and survival in oncology and have been linked to the discovery of novel treatment targets. This area of research in glioblastoma continues to evolve. The aim of this scoping review was to document the hallmark molecular characteristics of long-term survivors of glioblastoma. MEDLINE, Scopus and EMBASE were searched with core concepts: (1) glioblastoma, (2) long-term survivor and (3) molecular OR mutation. A thematic analysis was undertaken of the 18 included studies. Four main classes of characteristics were obtained: IDH mutation, MGMT methylation, other known characteristics and novel discoveries. While MGMT methylation or the combination with IDH mutation are suggested to be hallmark characteristics, there remains enough uncertainty to suggest further factors may be involved, such as CD34 expression. Further research is required to accurately describe hallmark molecular characteristics of long-term survivors to assist in defining these patients at diagnosis, preventing treatment complications and discovering novel treatments.


Assuntos
Neoplasias Encefálicas/genética , Sobreviventes de Câncer , Glioblastoma/genética , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Feminino , Glioblastoma/mortalidade , Humanos , Isocitrato Desidrogenase/genética , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Supressoras de Tumor/genética
18.
Gulf J Oncolog ; 1(21): 70-3, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27250893

RESUMO

Malignant melanoma of the anorectum is a rare but highly aggressive tumor. We report our experience of anorectal melanoma in five patients. Of these, two have advanced disease, two had localized disease and one patient had florid systemic metastases with a history of hemorrhoidectomy one year prior. One patient whose metastatic workup was negative, expired on post-op day 15 of abdominoperineal resection due to unsuspected but florid cerebral metastases. Another patient with localized disease underwent an APR with curative resection and post-op whole body PET scan negative for occult or residual disease. Advanced stage patients were referred for chemotherapy. To improve prognosis, it is important to detect anorectal melanoma at an early stage.


Assuntos
Neoplasias do Ânus/patologia , Melanoma/patologia , Neoplasias Retais/patologia , Humanos , Índia , Centros de Atenção Terciária
19.
Injury ; 46(9): 1749-52, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25813733

RESUMO

BACKGROUND: Post-traumatic residual haemothorax (RH) is common and carries significant morbidity. However, its optimal treatment is not clear. AIM: The aim of this study was to find the extent of this problem and the choice of treatment between VATS and intra-pleural streptokinase instillation (IPSI). MATERIAL AND METHODS: This RCT, conducted over 18 months period, included all patients of chest trauma between 18 and 70 years of age, admitted with haemothorax or haemopneumothorax requiring inter-costal drain (ICD) insertion. 154 events of haemothorax/haemopneumothorax requiring ICD insertion were enrolled. RH was seen in 48 (31%) patients: 13 patients were excluded from RCT after refusal for treatment. Seventeen (49%) patients of remaining 35 RH cases were randomized to IPSI group and 18 (51%) patients were randomized to VATS group. The outcome parameters were resolution of RH and treatment related complications. RESULTS: RH resolved equally well in VATS and IPSI group [13 patients (72%) versus 12 patients (71%), respectively; continuity-adjusted p=1]. Morbidity wise no difference (p-value 0.529) was seen in the two groups. CONCLUSION: Post-traumatic RH is seen in 1/3rd patients and is equally well treated by VATS and IPSI.


Assuntos
Fibrinolíticos/administração & dosagem , Hemotórax/terapia , Estreptoquinase/administração & dosagem , Traumatismos Torácicos/terapia , Cirurgia Torácica Vídeoassistida , Terapia Trombolítica , Ferimentos não Penetrantes/terapia , Adulto , Tubos Torácicos , Drenagem , Feminino , Hemotórax/tratamento farmacológico , Hemotórax/etiologia , Hemotórax/mortalidade , Hemotórax/cirurgia , Humanos , Índia/epidemiologia , Tempo de Internação , Masculino , Estudos Prospectivos , Traumatismos Torácicos/complicações , Traumatismos Torácicos/mortalidade , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/mortalidade
20.
J Cataract Refract Surg ; 23 Suppl 1: 681-7, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9278825

RESUMO

PURPOSE: To evaluate the presentation, mode of management, and clinical outcome of traumatic cataract in children. SETTING: L.V. Prasad Eye Institute, Hyderabad, India. METHODS: One hundred thirty-seven children (< 16 years) who developed traumatic cataract, seen between January 1988 and December 1993, were retrospectively analyzed. Nature of injury, type of cataract, management, and outcome were evaluated. RESULTS: The study group comprised 110 boys and 27 girls. Average follow-up was 11.7 months (range 1 week to 60 months). Most injuries (54.7%) were caused by a stick or a bow and arrow. Most (53.2%) of the cataracts were total. Corneal scarring (60.5%) and iris-related problems (49.6%) were the most common associated findings. Extracapsular cataract extraction with intraocular lens (IOL) implantation was performed in 65.67% of patients. Visual acuity improved form 20/200 or worse in 97.7% of patients preoperatively to 20/60 or better in 74.1% or patients postoperatively. Seventeen patients had associated posterior segment insult; most failed to recover satisfactory vision. Posterior capsule opacification (PCO) was noted in 42.9% of patients. CONCLUSIONS: Extracapsular cataract extraction with IOL implantation provides satisfactory results in children with traumatic cataract. Associated posterior segment complications and development of PCO are the major obstacles to visual rehabilitation.


Assuntos
Extração de Catarata , Catarata/terapia , Ferimentos Oculares Penetrantes/cirurgia , Cristalino/lesões , Adolescente , Catarata/etiologia , Criança , Pré-Escolar , Lesões da Córnea , Ferimentos Oculares Penetrantes/etiologia , Feminino , Humanos , Lactente , Cápsula do Cristalino/patologia , Lentes Intraoculares , Masculino , Complicações Pós-Operatórias , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual
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