RESUMO
BACKGROUND: Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. METHODS: We conducted a systematic review to identify all measures used to assess long-term neurocognitive outcomes following general anaesthesia (GA) and surgery in children. The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS) for observational studies. PubMed/MEDLINE, EMBASE, Cinahl, Web of Science, and the Cochrane Library were searched for studies investigating neurocognitive outcome after GA in children <18 yr. RESULTS: Sixty-seven studies were identified from 19 countries during 1990-2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other outcomes (magnetic resonance imaging, serum-biomarkers, mortality, neurological examination, measurement of head circumference, impairment of vision). Rating according to the NOS rewarded a mean of six stars out of nine. Some concerns prevail regarding potential inter-rater variability because of equivocal description of rating criteria. Specific features such as stability over lifetime and inter-relations of outcomes (e.g. prediction of subsequent development or diagnosis of neuropsychological conditions) are discussed. The importance of validity and reliability of the various test instruments are described. The studies vary immensely in important characteristics. CONCLUSIONS: Future observational studies should be more consistent in the choice of study population, age at exposure, follow-up, indication for and type of surgery, and outcomes. Assessment of sensory-motor development seems feasible in young children (age <4 yr), and intelligence/cognition in older children.
Assuntos
Anestésicos Gerais/efeitos adversos , Deficiências do Desenvolvimento/induzido quimicamente , Síndromes Neurotóxicas/etiologia , Complicações Pós-Operatórias/induzido quimicamente , Anestesia Geral/efeitos adversos , Humanos , Testes Neuropsicológicos , PsicometriaRESUMO
BACKGROUND: Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality. METHODS: This study aimed to identify the mutation present in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy. RESULTS: In all four, a novel mitochondrial m.8528T-->C mutation was identified. This results in a change of the initiation codon in ATPase 6 to threonine and a concurrent change from a highly conserved hydrophobic amino acid, tryptophan, at position 55 of ATPase 8 to a highly basic arginine. To our knowledge, this is the first report of a mutation affecting both mitochondrial genome-encoded complex V subunit proteins. Testing of the relatives of one patient indicated that the mutation is heteroplasmic and correlated with disease. CONCLUSION: Mitochondrial genome sequencing should be considered in patients with infantile hypertrophic cardiomyopathy.
Assuntos
Cardiomiopatia Hipertrófica/genética , ATPases Mitocondriais Próton-Translocadoras/genética , Mutação , Sequência de Bases , Cardiomiopatia Hipertrófica/enzimologia , Cardiomiopatia Hipertrófica/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Isovaleric acidemia, resulting from isovaleryl-coenzyme A dehydrogenase deficiency, is associated with marked reduction of free carnitine in both plasma and urine. Fast atom bombardment-mass spectrometry, hydrolysis, and gas chromatography/mass spectrometry have unequivocally identified the existence of isovalerylcarnitine, a new metabolite specific for this disorder. Administration of equimolar amounts of glycine or L-carnitine separately with leucine demonstrated that isovaleryl-coenzyme A is removed by supplemental L-carnitine in the form of isovalerylcarnitine as effectively as it is by glycine, in the form of isovalerylglycine. When L-carnitine is given alone, excretion of isovalerylglycine decreases in preference to enhanced excretion of isovalerylcarnitine and hippurate. Treatment with L-carnitine alone has proven effective in preventing further hospitalizations in a patient with this genetic disorder.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Carnitina/análogos & derivados , Carnitina/uso terapêutico , Oxirredutases atuantes sobre Doadores de Grupo CH-CH , Oxirredutases/deficiência , Ácidos Pentanoicos/sangue , Valeratos/sangue , Carnitina/urina , Pré-Escolar , Cromatografia por Troca Iônica , Glicina/uso terapêutico , Hemiterpenos , Humanos , Isovaleril-CoA Desidrogenase , Masculino , Espectrometria de MassasRESUMO
Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). FRAAs disrupt folate transport across the blood-brain barrier by binding to the FRα. Thyroid dysfunction is frequently found in children with ASD. We measured blocking and binding FRAAs and thyroid-stimulating hormone (TSH), free thyroxine (T4) (FT4), total triiodothyronine (T3) (TT3), reverse T3 (rT3), thyroid-releasing hormone (TRH) and other metabolites in 87 children with ASD, 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAAs, TSH and FT4 were measured at two time points. To better understand the significance of the FRα in relation to thyroid development, we examined FRα expression on prenatal and postnatal thyroid. TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT4 was rarely outside the normal range. TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT4/TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT4/TSH, TT3/TSH and rT3/TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale (SRS), whereas TT3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FRα expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA. The high expression of FRα in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAAs could affect the development of the thyroid and may contribute to the pathology in ASD.
Assuntos
Transtorno do Espectro Autista/epidemiologia , Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Receptor 1 de Folato/imunologia , Doenças da Glândula Tireoide/epidemiologia , Transtorno do Espectro Autista/sangue , Transtorno do Espectro Autista/complicações , Doenças Autoimunes/sangue , Doenças Autoimunes/complicações , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/complicações , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive reframing of autism as a multisystem disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism.
Assuntos
Transtorno Autístico/genética , Meio Ambiente , Genômica , Animais , Transtorno Autístico/epidemiologia , Bases de Dados Genéticas , HumanosRESUMO
Propionic acid (PPA) is a ubiquitous short-chain fatty acid, which is a major fermentation product of the enteric microbiome. PPA is a normal intermediate of metabolism and is found in foods, either naturally or as a preservative. PPA and its derivatives have been implicated in both health and disease. Whereas PPA is an energy substrate and has many proposed beneficial effects, it is also associated with human disorders involving mitochondrial dysfunction, including propionic acidemia and autism spectrum disorders (ASDs). We aimed to investigate the dichotomy between the health and disease effects of PPA by measuring mitochondrial function in ASD and age- and gender-matched control lymphoblastoid cell lines (LCLs) following incubation with PPA at several concentrations and durations both with and without an in vitro increase in reactive oxygen species (ROS). Mitochondrial function was optimally increased at particular exposure durations and concentrations of PPA with ASD LCLs, demonstrating a greater enhancement. In contrast, increasing ROS negated the positive PPA effect with the ASD LCLs, showing a greater detriment. These data demonstrate that enteric microbiome metabolites such as PPA can have both beneficial and toxic effects on mitochondrial function, depending on concentration, exposure duration and microenvironment redox state with these effects amplified in LCLs derived from individuals with ASD. As PPA, as well as enteric bacteria, which produce PPA, have been implicated in a wide variety of diseases, including ASD, diabetes, obesity and inflammatory diseases, insight into this metabolic modulator from the host microbiome may have wide applications for both health and disease.
Assuntos
Transtorno do Espectro Autista/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Mitocôndrias/fisiologia , Doenças Mitocondriais/fisiopatologia , Propionatos/metabolismo , Acidemia Propiônica/fisiopatologia , Estudos de Casos e Controles , Linhagem Celular , Criança , Humanos , MasculinoRESUMO
We present four patients with typical neonatal onset non-ketotic hyperglycinemia (NKH) who developed hydrocephalus requiring shunting in early infancy. Brain imaging revealed acute hydrocephalus, a megacisterna magna or posterior fossa cyst, pronounced atrophy of the white matter, and an extremely thin corpus callosum in all. The three older patients had profound developmental disabilities. This suggests that the development of hydrocephalus in NKH is an additional poor prognostic sign.
Assuntos
Hidrocefalia/diagnóstico por imagem , Hidrocefalia/patologia , Hiperglicinemia não Cetótica/diagnóstico por imagem , Hiperglicinemia não Cetótica/patologia , Doença Aguda , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XRESUMO
We report on four individuals in one kindred with relative or absolute short stature; increased upper/lower segment ratio with decreased arm span; mandibular prognathism and dental abnormalities; fractures following minimal trauma; mild to moderate anemia with extramedullary hematopoiesis; and radiographic changes of osteopetrosis, including sclerosis of the cranial base, generally increased bone density, sclerosis of the vertebral end plates, and transverse bands and poor diaphyseal modelling of the long bones. There is intrafamilial variability of clinical and radiographic findings in individuals with this mild, autosomal recessive form of osteopetrosis. We summarize ten families from the literature, which include 18 cases of mild recessive osteopetrosis. The manifestations of many are similar to those of the individuals reported here. Two other types of recessive osteopetrosis have been reported previously: osteopetrosis associated with renal tubular acidosis, and severe osteopetrosis with hepatosplenomegaly, pancytopenia, and early death. Autosomal dominant osteopetrosis is variable but usually mild. Pedigree analysis is currently the only reliable method of determining the pattern of inheritance in mild osteopetrosis.
Assuntos
Genes Recessivos , Osteopetrose/genética , Adulto , Estatura , Criança , Consanguinidade , Feminino , Humanos , Masculino , Osteopetrose/diagnóstico por imagem , Linhagem , RadiografiaRESUMO
The Brachmann-de Lange syndrome (BDLS) is diagnosed in children on the basis of a distinctive clinical phenotype which includes retarded physical growth. Because there are no genetic or biochemical tests at present, the antenatal detection of the syndrome may depend upon identification of some aspect of the phenotype in the fetus using ultrasound imaging. We studied the growth of 23 subsequently diagnosed fetuses with the BDLS using standard biometric parameters defined by prenatal ultrasound imaging. Sonographic studies were obtained through a national parents' group, the Cornelia de Lange Syndrome Foundation. Assessment of fetal growth was made using four standardized measurements: the biparietal diameter, head circumference, femur length, and abdominal circumference. These values were compared to established tables of normal fetal growth and established ratios of fetal body proportions. The cross-sectional growth curve derived using all measurements collected as a composite group indicates that growth retardation would be first detected as early as 25 weeks. In five fetuses with measurements both before and after 25 weeks of gestation, longitudinal growth curves indicated that the diagnosis of "small for gestational age" would have been suggested between 20 and 25 weeks. The mean fetal weight estimates closely followed the fifth centile curve of normal fetuses both before and after 25 weeks. Cephalic indices in BDLS fetuses indicated either frank brachycephaly (25%), or were at the upper portion of the normal range. Femur lengths were relatively short (less than 90% of their expected length) ion 4 of the 11 fetuses where such information could be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Síndrome de Cornélia de Lange/diagnóstico por imagem , Ultrassonografia Pré-Natal , Abdome/patologia , Estatura , Peso Corporal , Síndrome de Cornélia de Lange/patologia , Desenvolvimento Embrionário e Fetal , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Retardo do Crescimento Fetal/patologia , Feto/patologia , Idade Gestacional , Cabeça/patologia , Humanos , GravidezRESUMO
We report 4 cases and review 7 from the literature with a pattern suggesting a variable early lethal multiple congenital anomaly syndrome. This was first reported by von Voss et al. [1979: "Klinische Genetik in der Pädiatrie," pp 70-74] and Cherstvoy et al. [1980: Lancet ii:485], and can affect upper limbs, face, brain, heart, lungs, urogenital and gastrointestinal systems, vertebrae and ribs, and can include thrombocytopenia. The initial cases had occipital encephaloceles and phocomelia, but milder cerebellar anomalies and radial ray defects may be seen instead. Both sexes are affected and parental age is not increased. This may be heterogeneous, but two consanguineous families, one with recurrences, suggest autosomal recessive inheritance in at least some instances, although the recurrences had milder brain findings than the other cases. The original designation of DK-phocomelia syndrome is inaccurate, since arm findings may be limited to radial anomalies; we suggest instead the von Voss-Cherstvoy syndrome. This may be heterogeneous, but at present, phenotypic overlap prevents differentiation of subgroups. The disorder appears to be part of a group of syndromes with radial and hematologic abnormalities.
Assuntos
Anormalidades Múltiplas/genética , Consanguinidade , Ectromelia/complicações , Ectromelia/genética , Encefalocele/complicações , Encefalocele/genética , Feminino , Genes Letais , Genes Recessivos , Humanos , Recém-Nascido , Masculino , Fenótipo , Síndrome , Trombocitopenia/complicações , Trombocitopenia/genéticaRESUMO
We present a boy with a rare unbalanced translocation 46,XY,-15,+der(22),t(15;22)(q13;q11) pat. Previous reports of similar chromosome findings mention only the Prader-Willi phenotype. At birth, his manifestations included severe hypotonia and lethargy, (typical of deletion of 15pter----q13); hypertelorism, down-slanting small palpebral fissures, preauricular tags, long philtrum (typical of duplication of 22pter----q11); severe laryngotracheomalacia, and proximal implantation of the thumb. In a review of the literature on chromosome abnormalities involving duplication of 22q11 the associated clinical phenotype consists of mild mental retardation, microcephaly, hypotonia, hypertelorism, down-slanting palpebral fissures, a long philtrum, cleft or highly arched palate, and ear abnormalities. Preauricular pits or tags are common. Cardiovascular defects, renal and genital problems and dislocated hips are frequently present. Anal atresia and colobomata are mainly seen in cat-eye syndrome, the phenotype associated with idic 22q11. Our findings indicate that patients with unbalanced t(15;22) can have manifestations of the dup 22q11, in addition to the previously reported Prader-Willi phenotype, even if the duplicated segment is small.
Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 22 , Translocação Genética , Bandeamento Cromossômico , Deleção Cromossômica , Deformidades Congênitas da Mão/genética , Humanos , Recém-Nascido , Cariotipagem , Masculino , Família Multigênica , Literatura de Revisão como Assunto , SíndromeRESUMO
45,X/47,XYY mosaicism is a rare chromosomal disorder with clinical information limited to 11 postnatal cases in the literature and with uncertainty regarding prenatal prediction of phenotype and prognosis. We report on 7 new cases of 45,X/47,XYY mosaicism, three detected prenatally and 4 diagnosed postnatally. A clinical comparison of the cases of 45,X/47,XYY mosaicism is presented together with a literature review.
Assuntos
Mosaicismo , Síndrome de Turner/diagnóstico , Cariótipo XYY/diagnóstico , Amniocentese , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , GravidezRESUMO
Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by diaphragmatic hernia, unusual facies, and distal limb hypoplasia. It was first reported as a lethal condition. We report on a three-year-old survivor with Fryns syndrome, and provide a review on the outcome of other survivors. Patients who survive the neonatal period represent 14% of reported cases. Characteristics of survivors include less frequent diaphragmatic hernia and milder lung hypoplasia, absence of complex cardiac malformation, and neurologic impairment. Multiple central nervous system abnormalities have been reported in Fryns syndrome, including agenesis of the corpus callosum, Dandy-Walker abnormality, cerebellar heterotopias, cerebellar hypoplasia, enlarged ventricles, and hypoplasia of the olfactory bulbs. Our patient exhibited profound mental retardation. He had malformations of gyration and sulcation, particularly around the central sulcus, and hypoplastic optic tracts beyond the optic chiasm. Understanding of long-term outcome of survivors is important for counseling of families with Fryns syndrome. Careful brain examination is advised; however, a normal radiological brain examination does not preclude developmental delay. The spectrum of individual outcome and of associated anomalies indicates that individual evaluation, including imaging for structural brain malformation, is strongly advised.
Assuntos
Anormalidades Múltiplas/genética , Encéfalo/anormalidades , Face/anormalidades , Hérnia Diafragmática/genética , Deficiência Intelectual/genética , Pulmão/anormalidades , Encéfalo/patologia , Pé Torto Equinovaro/genética , Hérnias Diafragmáticas Congênitas , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , SíndromeRESUMO
Most congenital cutaneous hemangiomas are a sporadic occurrence. Hemangiomas have been found in association with coarctation of the aorta and a right aortic arch. A separate association has been noted of midline ventral defects with hemangiomas. We report on a patient with multiple hemangiomas, coarctation of the aorta and a right aortic arch, a superaumbilical midabdominal raphé and sternal cleft. Our patient represents an overlap between these two conditions. Review of the literature identified four additional patients with a similar combination of anomalies. The clinical overlap between these 5 patients suggests that they are variants of the same conditions and represent a spectrum of defects that includes hemangiomas, midline ventral defects, aortic arch abnormalities and brain malformation.
Assuntos
Aorta/anormalidades , Coartação Aórtica/genética , Encéfalo/anormalidades , Hemangioma/congênito , Feminino , Humanos , Recém-Nascido , SíndromeRESUMO
A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.
Assuntos
Ácido Aspártico/uso terapêutico , Ácido Cítrico/uso terapêutico , Doença da Deficiência de Piruvato Carboxilase/tratamento farmacológico , Aminoácidos/sangue , Aminoácidos/efeitos dos fármacos , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Lactente , Deficiência Intelectual/patologia , Cetose/sangue , Cetose/tratamento farmacológico , Ácido Láctico/sangue , Doença da Deficiência de Piruvato Carboxilase/sangue , Doença da Deficiência de Piruvato Carboxilase/patologia , Resultado do TratamentoRESUMO
Familial spastic paraplegia (FSP), characterized by progressive spasticity of the lower extremities, is in its "pure" form generally of autosomal dominant inheritance pattern. Hazan et al. [Nat Genet 5:163-167, 1993] reported tight linkage of a large FSP family to the highly polymorphic microsatellite marker D14S269 with z (theta) = 8.49 at theta = 0.00 They further demonstrated evidence for locus heterogeneity when they showed that 2 FSP families were unlinked to this region. We have subsequently studied 4 FSP families (3 American, one British) and excluded the disease locus in these families for approximately 30 cM on either side of D14S269, thereby confirming evidence for locus heterogeneity within the spastic paraplegia diagnostic classification.
Assuntos
Heterogeneidade Genética , Paraplegia/genética , Cromossomos Humanos Par 14 , DNA Satélite/análise , Feminino , Ligação Genética , Humanos , Escore Lod , Masculino , LinhagemRESUMO
Five patients presenting with non-ketotic hyperglycinemia in the neonatal period were treated with sodium benzoate to normalize plasma glycine levels. This therapy resulted in seizure reduction and a marked increase in wakefulness. Plasma carnitine deficiency was noted in three of four patients tested, and benzoylcarnitine was identified in plasma, urine, and CSF. Treatment with L-carnitine normalized plasma free carnitine. L-carnitine showed a tendency to increase the glycine conjugation of benzoate. An episode of coma and increased seizures in one patient was associated with a toxic level of benzoate, probably due to insufficient mobilization of glycine for conjugation. High dose benzoate therapy improved the quality of life of surviving patients. Close monitoring of glycine, benzoate and carnitine levels is advised.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Benzoatos/efeitos adversos , Carnitina/deficiência , Conservantes de Alimentos/efeitos adversos , Glicina/metabolismo , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Ácido Benzoico , Carnitina/uso terapêutico , Interações Medicamentosas , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Six children of similar ethnic origin with congenital myopathy, cleft palate, malignant hyperthermia (or susceptibility to malignant hyperthermia), and skeletal anomalies are presented. The findings are remarkably consistent among our patients, 3 of whom were related. This syndrome is likely to be inherited as an autosomal recessive trait. Children with this disorder are likely to undergo surgery with general anesthesia for facial or skeletal deformities and should be recognized as predisposed to developing malignant hyperthermia.
Assuntos
Osso e Ossos/anormalidades , Fissura Palatina/complicações , Hipertermia Maligna/etiologia , Doenças Musculares/congênito , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Doenças Musculares/complicações , SíndromeRESUMO
CONTEXT: Osteoarthritis (OA) is often treated with nonsteroidal anti-inflammatory drugs (NSAIDs) or selective inhibitors of cyclooxygenase-2 (COX-2). OBJECTIVE: This clinical trial aimed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen, named dexibuprofen (S(+)-ibuprofen) in a special crystal form, and the selective COX-2 inhibitor celecoxib in adults with OA of the hip. Moreover, the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested. METHODS: The investigation was a randomized, parallel-group, double-blind, active controlled clinical trial, conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria. 148 inpatients were randomly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily. The primary criterion was the improvement in the Western Ontario and' McMasters osteoarthritis index (WOMAC OA index) after 15 days of therapy. RESULTS: Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d. is not inferior to celecoxib 100 mg b.i.d. with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95% confidence interval equal to 0.4409. The overall incidence of adverse drug reactions was 12.16% in the dexibuprofen group and 13.51% in the celecoxib group. 8.1% of patients on dexibuprofen and 9.5% on celecoxib suffered from gastrointestinal disorders. CONCLUSION: In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Ibuprofeno/uso terapêutico , Osteoartrite do Quadril/tratamento farmacológico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Celecoxib , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Ibuprofeno/efeitos adversos , Ibuprofeno/química , Isoenzimas/antagonistas & inibidores , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Medição da Dor , Prostaglandina-Endoperóxido Sintases , Pirazóis , Índice de Gravidade de Doença , Estereoisomerismo , Sulfonamidas/efeitos adversos , Resultado do TratamentoRESUMO
Soft-tissue expansion in the lower extremities is typically well tolerated. The more proximal one is--that is, the closer to the thigh and buttocks--the easier and less complication prone the expansion will be. It is another valuable technique for resurfacing the lower extremity and for reconstructing defects in contour and in skin character. There are limitations to this technique, which generally is most useful in late reconstructions. Intraoperative expansion has no place in lower extremity reconstruction. Soft-tissue expansion may be limited by an unsuitable geometry or the sheer size of defects. It should not be used next to open wounds. Soft-tissue expansion offers significant advantage in that the coverage of a defect will be replaced with tissue like that lost. Seldom does one see necrosis of advanced flaps, so that there is little risk of tissue loss in using this modality. There is an excellent vascularity to the flaps and an excellent character to the skin. In addition, in this cost-conscious era, soft-tissue expansion is quite cost effective, and in many cases the procedures can be conducted on an outpatient basis with a minimum of hospitalization, if any. With care to select patients properly, design carefully, and conduct expansion in a leisurely fashion, soft-tissue expansion offers a valuable means of reconstructing both large and small lower extremity defects.