RESUMO
Autosomal dominant hypocalcemia (ADH) can result from heterozygous missense activating mutations of the calcium-sensing receptor (CaSR) gene, a G-protein-coupled receptor playing key roles in mineral ion metabolism. We now describe an ADH kindred of three generations caused by a novel CaSR mutation, a large in-frame deletion of 181 amino acids within its carboxylterminal-tail from S895 to V1075. Interestingly, the affected grandfather is homozygous for the deletion but no more severely affected than heterozygous affected individuals. Functional properties of mutant and wild-type (WT) CaSRs were studied in transiently transfected, fura-2-loaded human embryonic kidney (HEK293) cells. The mutant receptor exhibited a gain-of-function, but there was no difference between cells transfected with mutant complementary DNA alone or cotransfected with mutant and WT complementary DNAs, consistent with the similar phenotypes of heterozygous and homozygous family members. Therefore, this activating deletion may exert a dominant positive effect on the WT CaSR. The mutant receptor's cell surface expression was greater than that of the WT CaSR, potentially contributing to its gain-of-function. This novel mutation in the CaSR gene provides the first known examples of a large naturally occurring deletion within a G-protein-coupled receptor's carboxylterminal-tail and of a homozygous, affected individual with ADH.
Assuntos
Deleção de Genes , Hipocalcemia/genética , Receptores de Superfície Celular/genética , Adulto , Sequência de Bases , Linhagem Celular , Criança , Citoplasma/química , DNA Complementar/genética , Embrião de Mamíferos , Feminino , Heterozigoto , Homozigoto , Humanos , Recém-Nascido , Rim , Masculino , Pessoa de Meia-Idade , Linhagem , Receptores de Detecção de Cálcio , Análise de Sequência de DNA , TransfecçãoRESUMO
BACKGROUND: Antiamphiphysin antibodies react with a 128-kd protein found in synaptic vesicles. They were first described in patients with paraneoplastic stiff-man syndrome and breast cancer, but studies suggest that they can also occur in patients with other tumors and neurological disorders. OBJECTIVE: To determine if antiamphiphysin antibodies are associated with various paraneoplastic neurological syndromes and tumors. PATIENTS AND METHODS: Of 2800 serum samples tested by routine immunohistochemical procedures on sections of paraformaldehyde-fixed rat brain for the detection of autoantibodies associated with paraneoplastic neurological syndromes, 5 were selected because of labeling suggestive of antiamphiphysin antibodies and subsequently confirmed by the results of Western blot analysis using recombinant amphiphysin protein. Controls consisted of 40 patients with various nonparaneoplastic neurological diseases; 101 patients with cancer but without paraneoplastic neurological syndrome; 9 patients with small cell lung cancer, anti-Hu antibodies, and paraneoplastic neurological syndrome; 3 patients with M2-type antimitochondrial antibodies but no neurological disorder; and 30 normal subjects. RESULTS: Of the 5 patients with antiamphiphysin antibodies, patient 1 had sensory neuronopathy, encephalomyelitis, and breast cancer; patient 2 had limbic encephalitis, and small cell lung cancer was detected in the mediastinum after 24 months of follow-up; patient 3 had encephalomyelitis and ovarian carcinoma; and patients 4 and 5 had Lambert-Eaton myasthenic syndrome and small cell lung cancer (patient 4 subsequently developed cerebellar degeneration). None of the 5 had stiffness. Two patients (Nos. 2 and 4) had antimitochondrial antibodies. The two patients (Nos. 4 and 5) with Lambert-Eaton myasthenic syndrome had antibodies directed against the voltage-gated calcium channel, and patient 2 subsequently developed anti-Hu antibodies. In the controls, antiamphiphysin antibodies were detected by Western blot analysis in 3 of 8 patients with anti-Hu antibodies, but in none of the other groups. CONCLUSIONS: These data indicate that antiamphiphysin antibodies are not specific for one type of tumor or one neurological syndrome and can be associated with other neural and nonneural antibodies. The simultaneous association of several antibodies in some patients suggests multimodal autoantibody production.
Assuntos
Anticorpos Antineoplásicos/análise , Proteínas do Tecido Nervoso/imunologia , Doenças do Sistema Nervoso/imunologia , Neoplasias do Sistema Nervoso/imunologia , Síndromes Paraneoplásicas/imunologia , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RatosRESUMO
BACKGROUND: Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. METHODS: Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. RESULTS: The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). CONCLUSIONS: Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.
Assuntos
Ceftazidima/uso terapêutico , Cefalosporinas/uso terapêutico , Pielonefrite/tratamento farmacológico , Administração Oral , Cefepima , Ceftazidima/administração & dosagem , Cefalosporinas/administração & dosagem , Criança , Pré-Escolar , Quimioterapia Combinada/administração & dosagem , Quimioterapia Combinada/uso terapêutico , Feminino , Humanos , Lactente , Injeções Intravenosas , Masculino , Pielonefrite/microbiologia , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.
Assuntos
Dietilcarbamazina/efeitos adversos , Encefalite/induzido quimicamente , Loíase/tratamento farmacológico , Adolescente , Adulto , Dietilcarbamazina/administração & dosagem , Dietilcarbamazina/uso terapêutico , Feminino , Humanos , MasculinoRESUMO
Motor evoked potentials (MEP) were recorded in 23 patients with definite relapsing multiple sclerosis before and after treatment with a short course of high dose of methylprednisolone. MEP were performed together with clinical examination just before treatment, and 6 and 60 days later. The following results were observed: (1) a statistically significant relationship between the corticospinal deficit and the alteration in MEP, (2) a significant improvement in latency of MEP by day 6, (3) a significant correlation between the change in the Kurtzke disability scale rating and the improvement in MEP. The results provide further evidence for the possible effectiveness of short courses of high dose corticosteroids in the treatment of relapses of multiple sclerosis and the usefulness of MEP in its assessment.
Assuntos
Metilprednisolona/uso terapêutico , Neurônios Motores/fisiologia , Esclerose Múltipla/tratamento farmacológico , Adulto , Braço , Estimulação Elétrica , Potenciais Evocados/efeitos dos fármacos , Feminino , Humanos , Perna (Membro) , Masculino , Neurônios Motores/efeitos dos fármacos , Esclerose Múltipla/fisiopatologia , Contração MuscularRESUMO
Paraplegia caused by irreversible lesions of the spinal cord is one of the major possible complications after scoliosis surgery. Several monitoring methods have been proposed but none are completely satisfactory. Since 1986 the authors assessed motor pathways during scoliosis surgery, using electrical stimulation of the motor cortex and lower limb muscle recordings (tibialis anterior muscle). Twenty-seven patients were included in this study: 25 with idiopathic scoliosis and 2 with dorsal kyphosis. Recordings in anesthetized patients with hypothermia were performed before and after spinal derotation during the surgical procedure. Magnetic cortical stimulation was carried out in ten awake patients before and after surgery. Reproducible responses were obtained in 22 patients under anesthesia. In eight patients no difference of the latency of the muscle response was detected before and after the correction of the spinal angulation. In 14 patients the increase of latency ranged from 0.4 ms to 5.2 ms. No correlation was found between the slowing of motor conduction and the magnitude of spine correction. No central neurologic complications were seen after surgery. The authors concluded that their study demonstrated that motor pathway assessment in anesthetized patients can be performed at different times during the surgical procedure. This technique should help in the future monitoring spinal function during scoliosis surgery.
Assuntos
Cifose/cirurgia , Monitorização Intraoperatória , Córtex Motor/fisiologia , Escoliose/cirurgia , Adolescente , Estimulação Elétrica , Potenciais Evocados , Feminino , Humanos , Magnetismo , Masculino , Estimulação FísicaRESUMO
Central motor conduction was investigated by way of magneto-electric cortico-spinal stimulation in 6 patients with sporadic olivo-ponto-cerebellar atrophy. Two patients were found to have reduced leucocyte GDH activity. Only the 3 patients with corticospinal deficits displayed increased central conduction rates, which were predominant in the lower limbs. The duration of the disease is statistically longer in patients with corticospinal deficit compared to patients with no corticospinal deficit. In OPCA, evoked motor potentials are useful in assessing the corticospinal deficit which does not appear to be linked to reduced leucocyte GDH activity.
Assuntos
Glutamato Desidrogenase/sangue , Leucócitos/enzimologia , Condução Nervosa/fisiologia , Atrofias Olivopontocerebelares/fisiopatologia , Degenerações Espinocerebelares/fisiopatologia , Adulto , Estimulação Elétrica , Potenciais Evocados/fisiologia , Feminino , Humanos , Magnetismo , Masculino , Pessoa de Meia-Idade , Atrofias Olivopontocerebelares/sangue , Atrofias Olivopontocerebelares/enzimologiaRESUMO
Several epidemiologic studies of amyotrophic lateral sclerosis have shown a uniform repartition over the world. We report the results of a retrospective study and the preliminary results of a prospective study carried out in the Limousin area. The mean incidence per/year is 0.97/100,000 in the retrospective study and 1.3/100,000 in the prospective study. Such data are similar to those previously reported. The two major findings are the high frequency of bulbar palsy and the high mean age of the patients. This can be associated with the high mean age of the population in the Limousin area as compared to other regions.
Assuntos
Esclerose Lateral Amiotrófica/epidemiologia , Fatores Etários , França , Humanos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Evoked motor potentials can be elicited by magnetic cortical or electric spinal stimulations. The central conduction time (CCT) corresponds to the difference in latencies between the total conduction time (from cortex to muscle) and the peripheral conduction time (from spinal cord to muscle). CCT is the sum of the conduction time in the cortico-spinal fibers, of the spinal synaptic delay, and of the conduction time in the proximal part of the motor roots. CCT values (mean + standard deviation) were determined in 20 healthy subjects ranging from 21 to 56 years of age (mean 31.2). Results of magnetic cortical stimulation were compared to the results of electrical stimulation of the cortex. CCTs after magnetic cortical stimulation were longer than CCTs after electric cortical stimulation. This could be explained by the fact that electrical stimulation elicits a direct response in the cortico-spinal tract whereas magnetic cortical stimulation has indirect effects on the pyramidal cells of the motor cortex through excitatory interneurons. Compared with electrical stimulation, the magnetic stimulation has the great advantage of being painless and allows a safe evaluation of the central motor pathways in man.
Assuntos
Córtex Cerebral/fisiologia , Atividade Motora/fisiologia , Condução Nervosa , Tratos Piramidais/fisiologia , Medula Espinal/fisiologia , Adulto , Estimulação Elétrica , Potenciais Evocados , Humanos , Magnetismo , Pessoa de Meia-IdadeRESUMO
Ulnar nerve electrical stimulations from motor roots to wrist were used in the early Guillain-Barré syndrome (GBS), to improve the electrophysiological diagnosis yield. 22 patients with a GBS were investigated with this technique between 3 to 17 days after the onset. Conventional electrophysiological examination was sufficient to diagnose an Acute Inflammatory Demyelinating Polyneuropathy in 12 cases. In 10 other patients, standard examination remained negative or not conclusive, and vertebral electrical stimulations were decisive for the diagnosis, showing conduction bloks. This method could be routinely performed for an early diagnosis, in association with conventional motor conduction measurements. This study confirms the possibility of a pure proximal demyelinating impairment of the peripheral nervous system in the early GBS.
Assuntos
Estimulação Elétrica , Polirradiculoneuropatia/diagnóstico , Nervo Ulnar , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa , Polirradiculoneuropatia/fisiopatologia , Valores de Referência , Fatores de Tempo , Nervo Ulnar/fisiopatologiaRESUMO
Treatment of neonatal thrombocytopenia is dependent on its etiology and severity. The best indication for treatment with immunoglobulins is autoimmune thrombocytopenia. Platelet and blood transfusions are justified mainly in the presence of severe infection. The only indication for platelet transfusion is severe thrombocytopenia (platelet count below 30 G/L).
Assuntos
Trombocitopenia/terapia , Humanos , Recém-Nascido , Trombocitopenia/etiologiaRESUMO
UNLABELLED: Ischemic stroke in children is rare and its etiology is frequently unknown. CASE REPORT: We report the case of a nine-year-old boy who presented a right ischemic lenticular stroke due to neuroborreliosis, with a good outcome after antibiotic treatment. CONCLUSION: We suggest that it is important to search for neuroborreliosis in case of an ischemic stroke in children; the study of cerebral spinal fluid is a good diagnostic marker.
Assuntos
Isquemia Encefálica/etiologia , Neuroborreliose de Lyme/complicações , Isquemia Encefálica/diagnóstico por imagem , Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Criança , Humanos , Neuroborreliose de Lyme/tratamento farmacológico , Masculino , Paresia/etiologia , Paresia/reabilitação , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Megaloblastic anemia in children is mainly due to folic acid or vitamin B12 deficiencies. However dosages of these two vitamins must be performed before any vitamin supplementation or blood transfusions are given in order to establish precisely the etiologic diagnosis. A disorder in the metabolism of these vitamins must be considered in any infants in whom the onset of neurological abnormalities is associated with the characteristic hematological abnormalities. Imerslund's syndrome is a specific vitamin B12 malabsorption defect that warrants consideration as it is easy to recognize on the basis of the association of megaloblastic anemia and proteinuria. A possible drug-induced etiology must also be looked for. In the absence of vitamin deficiency, several rare etiologies must be considered. A macrocytosis, occasionally with megaloblastosis reflecting an abnormal erythropoiesis, may accompany an hemopathy, eventually malignant.
Assuntos
Anemia Megaloblástica , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/etiologia , Anemia Megaloblástica/fisiopatologia , Criança , Diagnóstico Diferencial , Deficiência de Ácido Fólico/complicações , Humanos , Lactente , Deficiência de Vitamina B 12/complicaçõesRESUMO
UNLABELLED: To assess pediatric cases of severe cutaneous infections due to Streptococcus pyogenes. Since the beginning of 1980, the incidence of cellulitis and necrotizing fasciitis due to S. pyogenes has increased in adults. Serotyping of obtained isolates are in most cases M1, M3 or M5 protein. PATIENTS AND METHOD: A retrospective (1990-2000) survey was carried out in pediatric hospital centers. RESULTS: Three cases of necrotizing fasciitis and 15 of cellulitis were observed. In 30% of the cases, vancella lesions were associated; in the other cases, minor wounds were the site of the infection. Bacteriologic diagnosis was made by local samples in 14 cases; blood cultures were positive in four cases. In 11 cases, initial intravenous treatment consisted of third generation cephalosporin, in six cases of penicillin M or G and in one case of fusidic acid. In the second time, penicillin M was perfused in the majority of the cases. Mean duration of intravenous antibiotics perfusion was 15 days. There were no sequelae or death in this survey. CONCLUSIONS: Despite this study had limited epidemiological characteristics, it confirms that these two infections are rare. The frequency is probably underestimated, due to the difficulty in performing a diagnosis. The major site of infection was the varicella lesion. These two infections are so similar that it is frequent to mistake one infection for the other. Nonsteroidal anti-inflammatory drugs and site of infections did not influence prognosis. The treatment of cellulitis is penicillinotherapy whereas in necrotizing fasciitis early major surgery is often correlated with the rate of survival.
Assuntos
Celulite (Flegmão)/epidemiologia , Fasciite Necrosante/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/tratamento farmacológico , Cefalosporinas/administração & dosagem , Varicela/diagnóstico , Varicela/tratamento farmacológico , Varicela/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/tratamento farmacológico , Feminino , Ácido Fusídico/administração & dosagem , Inquéritos Epidemiológicos , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Penicilinas/administração & dosagem , Estudos Retrospectivos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Superinfecção/diagnóstico , Superinfecção/tratamento farmacológico , Superinfecção/epidemiologiaAssuntos
Síndrome de Zellweger/diagnóstico por imagem , Encéfalo/patologia , Feminino , Humanos , Recém-Nascido , Ossos da Perna/diagnóstico por imagem , Imageamento por Ressonância Magnética , Hipotonia Muscular/complicações , Radiografia , Convulsões/complicações , Síndrome de Zellweger/diagnósticoRESUMO
Soluble antigens were looked for in 31 cases of purulent meningitis in children aged one day to 16 years. The latex technique was used in this study. Negative cases were controlled by counter-immune electrophoresis and by ELISA. From the results of our study and after a review of the literature, it appears that the latex technique is the best method at present to identify soluble antigens in purulent meningitis. This technique is better than a direct microscopic examination (p less than 0.02), especially in cases of meningitis due to H. influenzae and to S. pneumoniae. Latex technique kits used in the identification of type B meningococcus should be improved, and additional kits are needed if a wider range of bacteria are to be identified.