RESUMO
Cystinuria is a heterogeneous, rare but important cause of inherited kidney stone disease due to mutations in 2 genes: SLC3A1 and SLC7A9. Antenatal hyperechoic colon (HEC) has been reported in some patients as a non-pathological consequence of the intestinal transport defect. We report 83 patients affected by cystinuria: 44 presented prenatally with a HEC (HEC group) and 39 with a classical postnatal form (CC group). SLC3A1 and SLC7A9 were sequenced. All patients were fully genotyped, and the relationship between the genotype and clinical features was analyzed. We identified mutations in SLC3A1 in 80% of the HEC group and in only 49% of the CC group. The SLC3A1 p.Thr216Met mutation was found in 21% of the alleles in the HEC group but was never found in the CC group. Most of the mutations found in the HEC group were considered severe mutations in contrast with the CC group. Twenty-five novel mutations were reported. This study shows a relationship between genotype and the clinical form of cystinuria, suggesting that only the patients with the most severe mutations presented with an HEC. These results emphasized the need for prenatal cystinuria screening using classical third-trimester ultrasound scan and the early management of suspected newborns.
Assuntos
Sistemas de Transporte de Aminoácidos Básicos/genética , Sistemas de Transporte de Aminoácidos Neutros/genética , Colo/diagnóstico por imagem , Cistinúria/diagnóstico por imagem , Cistinúria/genética , Mutação , Alelos , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Colo/metabolismo , Colo/patologia , Cistinúria/metabolismo , Cistinúria/patologia , Éxons , Feminino , Feto , Expressão Gênica , Estudos de Associação Genética , Genótipo , Humanos , Recém-Nascido , Íntrons , Fenótipo , Gravidez , Terceiro Trimestre da Gravidez , UltrassonografiaRESUMO
INTRODUCTION: Patients with methylmalonic acidemia (MMA) may develop many complications despite medical treatment, in particular, severe central nervous system damage and chronic kidney disease (CKD). A kidney transplant may partially correct the metabolic dysfunctions. Liver, kidney and combined liver-kidney transplantations have been advocated but no guidelines are available to identify the most suitable organ to transplant. PATIENTS AND METHODS: Four patients with MMA (mut° phenotype) received a kidney graft because of repeated metabolic decompensations, with progression to CKD in 3 patients (end-stage kidney disease in two patients and CKD stage III in one patient with an estimated glomerular filtration rate [eGFR] of 40ml/min/1.73m(2)) but normal renal function in one (eGFR of 93ml/min/1.73m(2)) before transplantation. RESULTS: The medium age at transplantation was 7.9y (5-10.2) and the median follow-up was 2.8years (1.8-4.6). Renal transplantation improved the relevant metabolic parameters in 4/4 patients and renal function in the patients with CKD. Plasma and urinary MMA levels immediately decreased and remained normal or subnormal (mean values of plasma MMA before transplantation 1530µmol/L versus 240µmol/L after transplantation, and mean values of urine MMA before transplantation 4700mmol/mol creatinine versus 2300mmol/mol creatinine after transplantation). No further acute metabolic decompensation was observed and protein-intake was increased from 0.60 to 0.83g/Kg/day. One patient transplanted at age 9.7years developed a hepatoblastoma at age 11years with subsequent neurological complications and eventually died. The three other patients are alive. Two of them remained neurologically stable. The 3rd patient who displayed choreoathetosis transiently improved his neurological condition immediately after transplantation and then remained stable. CONCLUSION: Kidney transplantation represents an interesting alternative therapeutic option in methylmalonic aciduria, for renal complications but also as a "cellular therapy" that may significantly reduce metabolic decompensations and hospitalizations. However, further neurological impairment remains possible.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/terapia , Transplante de Rim , Transplante de Fígado , Doenças Metabólicas/terapia , Insuficiência Renal Crônica/terapia , Erros Inatos do Metabolismo dos Aminoácidos/sangue , Erros Inatos do Metabolismo dos Aminoácidos/genética , Erros Inatos do Metabolismo dos Aminoácidos/patologia , Erros Inatos do Metabolismo dos Aminoácidos/urina , Terapia Baseada em Transplante de Células e Tecidos , Criança , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Doenças Metabólicas/genética , Ácido Metilmalônico/sangue , Ácido Metilmalônico/urina , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/patologiaRESUMO
OBJECTIVES: To determine whether there is an association between the fetal ultrasound finding of hyperechoic colon and the gestational age at which it presents and cystinuria. METHODS: A prospective national survey was performed in France including all observations of isolated fetal hyperechoic colon detected at routine second- and third-trimester ultrasound over a 2-year period. Collected images were reviewed by experts. Colon was defined as being hyperechoic when its echogenicity was at least equal to that of the iliac bone. It was diagnosed when large tubular echogenic portions of the colon, without a focal mass and without posterior acoustic shadows, were observed at the periphery of the abdomen. Urinary amino acid analysis was performed after birth in the cases identified to test for cystinuria. RESULTS: Nineteen fetuses with ultrasound findings of hyperechoic colon were included, and the mothers of 16 of these agreed to participate in the study. In eight of nine cases of hyperechoic colon observed before 36 weeks' gestation cystinuria was confirmed at birth. In the seven remaining cases, observed after 36 weeks, none was found to have cystinuria and all had normal images at previous routine ultrasound scans at 22 and 33 weeks. When present, no difference in the sonographic appearance of hyperechoic colon was noted between the two groups. In the cystinuria-affected cases, the length of the hyperechoic mass appeared to increase with gestational age. CONCLUSIONS: In our experience, the presence of a hyperechoic colon at routine ultrasound scan before 36 weeks' gestation should prompt screening for cystinuria at birth, while later observation (> 36 weeks) of this finding does not appear to be related to any disease.
Assuntos
Aminoácidos/urina , Colo/diagnóstico por imagem , Cistinúria/diagnóstico por imagem , Doenças Fetais/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Colo/anormalidades , Colo/embriologia , Cistinúria/embriologia , Cistinúria/urina , Feminino , Doenças Fetais/urina , França , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez , Estudos ProspectivosRESUMO
A 22 year-old woman with tyrosinemia type I (HT1) married her first cousin who is heterozygous for the same FAH mutation for which the patient is homozygous. During her pregnancy she was treated with diet (prescribed tyrosine intake 300 mg/day), and nitisinone (60 mg/day). Median plasma tyrosine levels were 560 µmol/L (range: 375-838, n = 21) and nitisinone 51 µmol/L (range: 41-57, n = 3) during pregnancy. She gave birth to a clinically healthy girl affected with tyrosinemia type 1. Birth was normal (birth weight 2615 g) and the baby had normal liver function, normal plasma alpha-fetoprotein concentrations, low urinary excretion of phenolic acids and no detectable succinylacetone. At birth, the baby had hypertyrosinemia (860 µmol/L in blood cord) and nitisinone levels of 14 µmol/L. Following molecular confirmation of the diagnosis of HT1 specific treatment began on day 15 by which time she had detectable urinary succinylacetone.
Assuntos
Hidrolases/genética , Mutação , Tirosinemias/genética , Biomarcadores/sangue , Biomarcadores/urina , Desenvolvimento Infantil , Consanguinidade , Cicloexanonas/uso terapêutico , Análise Mutacional de DNA , Dieta com Restrição de Proteínas , Feminino , Predisposição Genética para Doença , Heptanoatos/sangue , Heptanoatos/urina , Hereditariedade , Heterozigoto , Homozigoto , Humanos , Hidrolases/metabolismo , Lactente , Recém-Nascido , Nascido Vivo , Nitrobenzoatos/uso terapêutico , Linhagem , Fenótipo , Gravidez , Tirosina/sangue , Tirosinemias/diagnóstico , Tirosinemias/enzimologia , Tirosinemias/terapia , Adulto JovemRESUMO
OBJECTIVE: To better delineate the natural history of patients with methylmalonic aciduria (MMA). STUDY DESIGN: Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4-19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies. RESULTS: Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5-18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2-7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut(o), 3 mut- and 5 cblA. Mortality, number of acute decompensations (p=0.031), median MMA urinary excretion (p=0.006) and neurological impairment (p<0.0001) were higher in mut degrees patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut(o) patients and was more severe. CONCLUSIONS: Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut(o) phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/terapia , População Branca , Adolescente , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/complicações , Erros Inatos do Metabolismo dos Aminoácidos/urina , Criança , Pré-Escolar , Progressão da Doença , Feminino , França , Humanos , Lactente , Rim/patologia , Falência Renal Crônica/complicações , Falência Renal Crônica/patologia , Masculino , Ácido Metilmalônico/urina , Doenças do Sistema Nervoso/complicações , Fenótipo , Fatores de Tempo , Resultado do TratamentoRESUMO
UNLABELLED: Hyperargininaemia is a rare inborn error of metabolism due to a defect in the final step of the urea cycle. Infantile onset is the most common presentation with recurrent vomiting and psychomotor delay associated with spastic paraparesis; chronic hyperammonaemia is often overlooked. Neonatal and early-onset presentations are very uncommon and their clinical course not well-described. We report on a 3-week-old hyperargininaemic girl who presented with neurological deterioration associated with liver failure and 47-day ammonia intoxication before diagnosis could be made and treatment started. Despite appropriate but delayed treatment, our patient exhibited severe psychomotor delay at age 1 year. CONCLUSION: Early identification and management of this rare but potentially treatable affection is crucial as delayed management may result in poor neurological outcome.
Assuntos
Hiperargininemia/diagnóstico , Idade de Início , Diagnóstico Tardio , Dieta com Restrição de Proteínas , Diagnóstico Precoce , Feminino , Humanos , Hiperargininemia/complicações , Hiperargininemia/patologia , Lactente , Recém-Nascido , Transtornos Psicomotores/etiologiaRESUMO
An adult patient with methylmalonic aciduria due to defective cobalamin synthesis (CblA) responsive to vitamin B(12) presented suddenly with severe visual impairment ascribed to optic atrophy followed by a fatal multiorgan failure and lactic acidosis but low methylmalonic acid in plasma and urine. Multiple deficiency of oxidative phosphorylation was found in the patient's liver. We suggest that patients with B(12)-sensitive methylmalonic aciduria who have a milder clinical course should be carefully monitored for long-term complications.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico , Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Fígado/metabolismo , Ácido Metilmalônico/urina , Fosforilação Oxidativa , Vitamina B 12/uso terapêutico , Vitamina B 12/urina , Adulto , Erros Inatos do Metabolismo dos Aminoácidos/genética , Ciclo do Ácido Cítrico/fisiologia , DNA Mitocondrial/química , DNA Mitocondrial/genética , Transporte de Elétrons/fisiologia , Evolução Fatal , Humanos , Fígado/patologia , Masculino , Músculo Esquelético/patologiaRESUMO
A boy who was diagnosed with methylmalonic aciduria (MMA) at the age of 10 days developed persistent hepatomegaly and raised transaminases from the age of 4 years. He was subsequently diagnosed with Leigh syndrome and required a kidney transplantation for end-stage renal failure. A massive hepatoblastoma led to his death by the age of 11 years. Methylmalonyl-CoA mutase activity was undetectable on both cultured skin fibroblasts and kidney biopsy and multiple respiratory chain deficiency was demonstrated in the kidney. Mitochondrial dysfunction and/or post-transplant immunosuppressive therapy should be considered as a possible cause of liver cancer in this patient.
Assuntos
Hepatoblastoma/enzimologia , Erros Inatos do Metabolismo Lipídico/complicações , Erros Inatos do Metabolismo Lipídico/enzimologia , Metilmalonil-CoA Mutase/metabolismo , Células Cultivadas , Criança , Transporte de Elétrons , Evolução Fatal , Fibroblastos/enzimologia , Seguimentos , Hepatoblastoma/etiologia , Hepatoblastoma/genética , Hepatoblastoma/terapia , Humanos , Imunossupressores/efeitos adversos , Rim/enzimologia , Rim/metabolismo , Transplante de Rim/efeitos adversos , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/terapia , Masculino , Ácido Metilmalônico/metabolismo , Metilmalonil-CoA Mutase/genética , MutaçãoRESUMO
AIM: In pyridoxine dependent epilepsy (PDE), patients usually present with neonatal seizures. A small subgroup is characterized by late-onset beyond 2 months of age. We aim to analyze the observation of relatively good cognitive outcome in this subgroup of late-onset PDE patients. METHODS: We retrospectively analyzed data from four metabolically and genetically confirmed late-onset patients with PDE due to antiquitin (ALDH7A1) deficiency. Data were analyzed regarding ALDH7A1 mutations, alpha-Aminoadipic semialdehyde (α-AASA) and pipecolic acid (PA) levels, medication during pregnancy, delivery, treatment delay, amount of seizures, pyridoxine dose, adjuvant therapy and findings on brain MRI. RESULTS: Results showed that three patients had relatively good outcome (IQ 80-97), while one patient did not undergo formal testing and was considered mildly delayed. We were unable to find a clear association between the above-mentioned variables and cognitive outcome, although a less severe genotype may be present in three patients, and maternal medication could be accountable for better outcome in two patients. INTERPRETATION: We suggest that favorable outcome in late onset PDE might be explained by a combination of factors. A yet unknown protective factor, different genetic variations, functional variation and secondarily variation in treatment regimens and absence of neonatal seizure induced brain damage.
Assuntos
Idade de Início , Epilepsia/complicações , Deficiência Intelectual/genética , Aldeído Desidrogenase/genética , Epilepsia/genética , Feminino , Genótipo , Humanos , Lactente , Deficiência Intelectual/epidemiologia , Inteligência/genética , Imageamento por Ressonância Magnética , Masculino , Mutação , Piridoxina/uso terapêutico , Estudos RetrospectivosRESUMO
Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective mu receptor agonist), nor ibotenate plus naloxone (a classical opioid receptor antagonist) modulated the excitotoxic lesion. Pretreatment with antisense oligonucleotides targeting the NC precursor peptide mRNA significantly reduced ibotenate-induced white-matter damage. Finally, high doses of fentanyl, which stimulates both classical mu-opioid receptors and ORL1, exacerbated excitotoxic white-matter lesion. This toxic effect was blocked by inhibiting ORL1 but not classical opioid receptors. Together, these findings show that endogenous or exogenous stimulation of the ORL1 receptor can be neurotoxic and that blocking NC signaling protects the white matter against excitotoxic challenge. These data point to potential new avenues for neuroprotection in human preterm infants at high risk of brain lesions.
Assuntos
Encéfalo/efeitos dos fármacos , Ácido Ibotênico/toxicidade , Peptídeos Opioides/toxicidade , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Fentanila/farmacologia , Humanos , Recém-Nascido , Leucomalácia Periventricular/etiologia , Camundongos , Naloxona/farmacologia , Oligonucleotídeos Antissenso/metabolismo , Oligonucleotídeos Antissenso/uso terapêutico , Receptores de N-Metil-D-Aspartato/fisiologia , NociceptinaRESUMO
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.
Assuntos
Corpo Estriado/diagnóstico por imagem , Encefalomiopatias Mitocondriais , Irmãos , Substância Negra/diagnóstico por imagem , Adulto , Corpo Estriado/patologia , Doenças em Gêmeos , Éxons , Humanos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Encefalomiopatias Mitocondriais/diagnóstico por imagem , Encefalomiopatias Mitocondriais/genética , Encefalomiopatias Mitocondriais/fisiopatologia , Encefalomiopatias Mitocondriais/urina , Mutação , Condução Nervosa/fisiologia , Cintilografia , Análise de Sequência de DNA/métodos , Substância Negra/patologia , Timidina/urina , Timidina Fosforilase/genéticaRESUMO
The diagnosis of certain metabolic diseases is problematic because it cannot be achieved with conventional blood and urine analyses but requires cerebrospinal fluid (CSF) study. CSF analysis is essential for the diagnosis of neurotransmitter metabolic disorders (synthesis defects of biogenic monoamines, non ketotic hyperglycinemia and homocarsinosis), defects of specific transporters (glucose cerebral transporter (Glut1) deficiency and cerebral folate deficiency) and is of help for the diagnosis of disorders of cerebral energy metabolism (respiratory chain disorders and pyruvate dehydrogenase deficiency). Our goal is to give an outline of hereditary metabolic diseases whose diagnosis is based on CSF analysis. We will detail late onset clinical forms which may be first seen in an adult neurology department.
Assuntos
Erros Inatos do Metabolismo/líquido cefalorraquidiano , Erros Inatos do Metabolismo/diagnóstico , Adulto , Metabolismo Energético/fisiologia , Humanos , Neurotransmissores/líquido cefalorraquidiano , Proteínas de Transporte de Neurotransmissores/líquido cefalorraquidianoRESUMO
Pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive metabolic disease characterized by seizures in neonates or infants, which is unresponsive to antiepileptic drugs but controlled by pyridoxine. Without prompt treatment, continued seizures and severe encephalopathy result. Mutations in the ALDH7A1 gene encoding α-amino-adipic semialdehyde (α-AASA) dehydrogenase (antiquitin) have been identified as the cause of PDE. We report on a novel ALDH7A1 mutation in a Tunisian child with PDE.
Assuntos
Análise Mutacional de DNA , Epilepsia/genética , Encéfalo/patologia , Pré-Escolar , Aberrações Cromossômicas , Consanguinidade , Corpo Caloso/patologia , Epilepsia/diagnóstico , Epilepsia/terapia , Feminino , Genes Recessivos , Triagem de Portadores Genéticos , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Exame Neurológico , TunísiaRESUMO
The cobalamin type C deficiency is a rare condition that results from impaired biosynthesis of both methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl). Hemizygous mutations of the HCFC1 gene explain the majority of clinically and biologically compatible cblC patients without MMACHC mutations (OMIM 309541). We report a family with two maternal half-brothers with multiple congenital anomalies and HCFC1 gene mutation in the second Kelch domain. Both presented with dysmorphic features (flat profile, cleft lip for one), increased nuchal translucency, prenatal onset microcephaly and hypospadias. Additionally to early onset intractable epilepsy and profound neurocognitive impairment, this familial observation suggests that HCFC1 gene should be considered in boys with midline malformations, even without proven cobalamin C deficiency.
Assuntos
Anormalidades Múltiplas/genética , Fator C1 de Célula Hospedeira/genética , Deficiência de Vitamina B 12/genética , Anormalidades Múltiplas/diagnóstico , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Pré-Escolar , Fenda Labial/genética , Cobamidas/biossíntese , Hibridização Genômica Comparativa , Testes Genéticos , Fator C1 de Célula Hospedeira/metabolismo , Humanos , Cariotipagem , Masculino , Mutação , Oxirredutases , Vitamina B 12/análogos & derivados , Vitamina B 12/biossíntese , Deficiência de Vitamina B 12/diagnósticoRESUMO
Mutations in the MUT locus encoding for the methylmalonyl-CoA mutase (MCM) apoenzyme are responsible for the mut forms of methylmalonic acidemia (MMA). To date, 49 different mutations have been identified in mut MMA. Only two frequent mutations have been reported in the Japanese population and in African-Americans. Here we report a new missense mutation N219Y (731 A-->T) which we found in five unrelated families of French and Turkish descent. All the patients exhibited a severe mut(degree) phenotype and three of them were homozygotes for N219Y. Direct involvement of the mutation in the loss of enzyme activity was demonstrated by mutagenesis and transient expression study. Mapping of the mutation onto a three-dimensional model of human MCM constructed by homology with the Propionibacterium shermanii enzyme shows that it lies in a highly conserved secondary structure motif and might suggest impaired folding and/or poor stability compatible with the mut(degree) phenotype. Finally, a 1% N219Y carrier frequency was observed in a French anonymous control population. Thus, N219Y is the first frequent mut mutation to be reported in the Caucasian population.
Assuntos
Substituição de Aminoácidos/genética , Erros Inatos do Metabolismo Lipídico/genética , Ácido Metilmalônico/sangue , Mutação de Sentido Incorreto/genética , População Branca/genética , Sequência de Aminoácidos , Asparagina/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Erros Inatos do Metabolismo Lipídico/sangue , Erros Inatos do Metabolismo Lipídico/enzimologia , Masculino , Ácido Metilmalônico/metabolismo , Metilmalonil-CoA Mutase/genética , Metilmalonil-CoA Mutase/metabolismo , Dados de Sequência Molecular , Tirosina/genéticaRESUMO
OBJECTIVES: To describe the initial evolution of serum procalcitonin (PCT) and C-reactive protein (CRP) in previously healthy adult trauma patients and to compare the relationship of the expression of these two proteins with indicators of trauma severity. DESIGN: Prospective, descriptive, longitudinal study. SETTING: Surgical ICU in an university hospital. PATIENTS: Twenty-one patients admitted during the first posttraumatic 3 h exhibiting an Injury Severity Score (ISS) between 16 and 50 were enrolled. MEASUREMENTS: Blood sampling was performed on admission and on posttraumatic days 0.5, 1, 2 and 3 to assess serum levels of PCT and CRP. Total creatine kinase (CKtot) and lactate dehydrogenase (LDHtot) activities in the serum were used as tissue damage indicators. RESULTS: PCT exhibited an early and transient increase in serum levels similar to a more delayed change of CRP levels. Peak PCT and peak CRP were related to the ISS, the extent of tissue damage and the amount of fluid replacement during the first day. During the first 3 posttraumatic days, 90% of the patients exhibited a generalized inflammatory syndrome without infection. CONCLUSIONS: An early and transient release of PCT into the circulation was observed after severe trauma and the amount of circulating PCT seemed proportional to the severity of tissue injury and hypovolemia, yet unrelated to infection. The predictive value of both PCT and CRP for a forthcoming multiple organ failure still remains to be clarified.
Assuntos
Proteína C-Reativa/metabolismo , Calcitonina/sangue , Precursores de Proteínas/sangue , Ferimentos e Lesões/imunologia , Adulto , Peptídeo Relacionado com Gene de Calcitonina , Creatina Quinase/sangue , Feminino , Humanos , Escala de Gravidade do Ferimento , L-Lactato Desidrogenase/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ferimentos e Lesões/enzimologiaRESUMO
OBJECTIVE: To investigate the effects of low-dose dopamine (Dop) on renal hemodynamics and function in patients with brain trauma receiving norepinephrine (NE). DESIGN: Prospective clinical study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 stable, non-septic, mechanically ventilated, sedated patients with brain trauma and normal renal function treated with intravenous NE (0.11-0.65 microg/kg per min) to maintain an adequate cerebral perfusion pressure (> 60 mmHg). INTERVENTIONS: Two successive 1-h study periods with NE alone then NE + Dop (2 microg/kg per min). During each period, creatinine (Cl(CREAT)), sodium (Cl(Na)), potassium (Cl(K)), osmolar (Cl(OSM)) and free water (Cl(H2O)), clearances were measured in all the patients. Effective renal blood flow (ERBF, para-aminohippurate clearance) and glomerular filtration rate (GFR, inulin clearance) were measured in 7 of the 20 patients. RESULTS: Dop during NE infusion induced increases in urine flow and natriuresis which were not correlated with possible changes in arterial pressure. Cl(CREAT), GFR and their difference remained unchanged, whereas ERBF tended to increase. Fractional sodium excretion [100 x (Cl(Na)/Cl(CREAT)] and C1(K) increased during Dop infusion. CONCLUSION: The mechanism of Dop-induced natriuresis during NE infusion in brain trauma patients seems mainly related to a direct tubular effect of the drug.
Assuntos
Lesões Encefálicas/fisiopatologia , Cardiotônicos/farmacologia , Dopamina/farmacologia , Hipertensão Intracraniana/tratamento farmacológico , Rim/efeitos dos fármacos , Vasoconstritores/farmacologia , Adolescente , Agonistas alfa-Adrenérgicos/administração & dosagem , Agonistas alfa-Adrenérgicos/farmacologia , Adulto , Lesões Encefálicas/terapia , Cardiotônicos/administração & dosagem , Dopamina/administração & dosagem , Feminino , Escala de Coma de Glasgow , Hemodinâmica/efeitos dos fármacos , Humanos , Escala de Gravidade do Ferimento , Pressão Intracraniana , Rim/fisiopatologia , Masculino , Norepinefrina/administração & dosagem , Norepinefrina/farmacologia , Estudos Prospectivos , Vasoconstritores/administração & dosagemRESUMO
OBJECTIVES: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients. DESIGN: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital. METHODS: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiographic (TEE) recordings. RESULTS: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35%) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83% vs 18%, p = 0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p = 0.027) and usually demonstrated early (83% vs 9%, p = 0.005) and late (66% vs 9%, p = 0.028) multiple organ dysfunction syndrome. CONCLUSIONS: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock.
Assuntos
Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/diagnóstico , Miocárdio/química , Índices de Gravidade do Trauma , Troponina I/sangue , Adulto , Biomarcadores/sangue , Creatina Quinase/sangue , Cuidados Críticos/métodos , Feminino , Traumatismos Cardíacos/enzimologia , Hemodinâmica/fisiologia , Humanos , Isoenzimas , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Traumatismo Múltiplo/sangue , Traumatismo Múltiplo/diagnóstico , Traumatismo Múltiplo/fisiopatologia , Prognóstico , Estudos Prospectivos , Análise de Regressão , Rabdomiólise/sangue , Rabdomiólise/diagnóstico , Fatores de TempoRESUMO
The diagnosis of infection in systemic inflammatory syndrome response is difficult but essential for correct patient management. Procalcitonin is a new biochemical marker of infection especially for bacterial infection. Procalcitonin and C-reactive protein (CRP) were prospectively studied in 21 severe trauma patients and correlated with the trauma severity and the occurrence of infection. At the early post-traumatic period (admission to day 3) procalcitonin and CRP are correlated with the severity of trauma (early volume loading and markers of tissue injury) as did typically acute inflammatory proteins. At the late post-traumatic period (day 7) while CRP concentrations remain elevated in all patients, procalcitonin concentrations are only raised in septic patients even if inflammation's clinical signs persist.