RESUMO
BACKGROUND: Interferon-gamma release assays (IGRAs) have high specificity and sensitivity for the diagnosis of tuberculosis (TB) infection. However, their role as a screening tool in children with immunodeficiency disorders is still unclear. In the present study, we performed a contact investigation using serial IGRAs on children with immunodeficiency conditions exposed to a contagious TB patient. METHODS: Children who were exposed to a contagious TB case underwent serial QuantiFERON(®) TB Gold In-Tube (QFT-GIT) and T-SPOT(®).TB (T-SPOT) testing. RESULTS: Eighteen children were tested. At the first testing, only two children (11 %) were positive to T-SPOT. Indeterminate results were more frequent with QFT-GIT (35 %) than with T-SPOT (12 %). In the multivariable analysis, a statistically significant association of lymphocyte count <500 cells/mm(3) (p < 0.00005) and low age (p = 0.03) with indeterminate results for the QFT-GIT test but not for T-SPOT (p = 0.10 and p = 0.88, respectively) was found. At the end of October 2012, 15 of the 18 children were alive and none developed active TB disease. CONCLUSION: T-SPOT provided more determinate results and was less influenced by low age and lymphocytopenia than QFT-GIT in this population of immunodeficient children. These findings suggest that T-SPOT is a more accurate test for the identification of TB infection in young children with lymphocytopenia and should be preferred to QFT-GIT under such specific conditions.
Assuntos
Busca de Comunicante/métodos , Testes de Liberação de Interferon-gama/métodos , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/transmissão , Adolescente , Criança , Pré-Escolar , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/transmissão , Feminino , Neoplasias Hematológicas/complicações , Humanos , Lactente , Masculino , Programas de Rastreamento/métodos , Adulto JovemRESUMO
BACKGROUND: Oral mucositis is a common complication in pediatric cancer patients, affecting up to 80% of children. Due to neutropenia and disruption of the mucosal barrier, chemotherapy-induced oral mucositis is often complicated by super-infections. CASE REPORT: A 16-years old male with stage 3 Burkitt's lymphoma developed chemotherapy induced oral mucositis grade 3 (according to WHO scale). Ulcers were quickly growing (reaching a maximum diameter of 3 cm) and became greyish in colour, resulting in dysphagia and pain. A swab of the lesions was taken and microbiological tests were performed. The sample grew for Raoultella planticola, an encapsulated Gram-negative bacterium whose full pathogenic potential still needs to be defined. TREATMENT: The patient received antibiotic combination therapy with Amikacin and Ceftazidime for 8 days. Complete healing of the lesions and resolution of the symptoms were reached and he completed his antineoplastic therapy without further complications. FOLLOW-UP: Twelve months after the infection, he is alive and well, with no oral complaints. CONCLUSION: This is the first report of a Raoultella planticola infection in a patient with chemotherapy induced oral mucositis. This type of infection must be added to the list of organisms to be considered when caring for these patients.
Assuntos
Linfoma de Burkitt/complicações , Infecções por Enterobacteriaceae/etiologia , Enterobacteriaceae , Estomatite/etiologia , Adolescente , Amicacina/administração & dosagem , Amicacina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Ceftazidima/administração & dosagem , Ceftazidima/uso terapêutico , Quimioterapia Combinada , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Humanos , Masculino , Estomatite/tratamento farmacológico , Estomatite/microbiologiaRESUMO
PURPOSE: To report on the treatment of patients with newly diagnosed neuroblastoma presenting with spinal cord compression (SCC). PATIENTS AND METHODS: Of 1,462 children with neuroblastoma registered between 1979 and 1998, 76 (5.2%) presented with signs/symptoms of SCC, including motor deficit in 75 patients (mild in 43, moderate in 22, severe [ie, paraplegia] in 10), pain in 47, sphincteric deficit in 30, and sensory loss in 11. Treatment of SCC consisted of radiotherapy in 11 patients, laminectomy in 32, and chemotherapy in 33. Laminectomy was more frequently performed in cases with favorable disease stages and in those with severe motor deficit, whereas chemotherapy was preferred in patients with advanced disease. RESULTS: Thirty-three patients achieved full neurologic recovery, 14 improved, 22 remained stable, and eight worsened, including three who become paraplegic. None of the 10 patients with grade 3 motor deficit, eight of whom were treated by laminectomy, recovered or improved. In the other 66 patients, the neurologic response to treatment was comparable for the three therapeutic modalities. All 11 patients treated by radiotherapy and 26 of 32 patients treated by laminectomy, but only two of 33 treated by chemotherapy, received additional therapy for SCC. Fifty-four of 76 patients are alive at time of the analysis, with follow-up of 4 to 209 months (median, 139 months). Twenty-six (44%) of 54 survivors have late sequelae, mainly scoliosis and sphincteric deficit. CONCLUSION: Radiotherapy, laminectomy, and chemotherapy showed comparable ability to relieve or improve SCC. However, patients treated with chemotherapy usually did not require additional therapy, whereas patients treated either with radiotherapy or laminectomy commonly did. No patient presenting with (or developing) severe motor deficit recovered or improved. Sequelae were documented in 44% of surviving patients.
Assuntos
Neuroblastoma/patologia , Neuroblastoma/terapia , Compressão da Medula Espinal/terapia , Neoplasias da Medula Espinal/patologia , Neoplasias da Medula Espinal/terapia , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Laminectomia , Masculino , Invasividade Neoplásica , Neuroblastoma/mortalidade , Compressão da Medula Espinal/tratamento farmacológico , Compressão da Medula Espinal/radioterapia , Neoplasias da Medula Espinal/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Defects of the JAK3-gene are known to cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T-B+SCID). The JAK3 protein, an intracellular tyrosine kinase, is crucial for signal-transmission from the common gamma chain to the Signal Transducers and Activators of Transcription (STATs) that drive gene expression in the nucleus. We present nine novel patients with eleven distinct mutations (g.96A>G, g.268G>C, IVS12-1G>A, g.2046C>T, g.2160C>T, g.2175G>A, g.2187G>T, g.2391C>T, g.2406C>T, IVS18+3G>C) among them a mutation in the kinase domain (JH1: g.3167del). The clinical phenotype of the patients shows an unusually broad spectrum ranging from classical SCID to almost normal. In order to understand the complex genotype-phenotype correlation we studied expression and function (by IL-2 induced phosphorylation) of the newly identified and two other alleles with JH1 mutations we recently reported. We found the first mutation in the JH1-domain of JAK3, that precludes kinase activity (L910S). The two other JH1 mutations both caused a premature stop. One of them (C1024fsX1037) also abolished any phosphorylation of JAK3 and expression of the protein. The other mutation (Y1023X), affecting the last JH1 tyrosine, may allow for residual protein expression and phosphorylation. This may indicate that the part of the kinase region downstream Y1023, is not essential for the function of JAK3.
Assuntos
Mutação/genética , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/genética , Alelos , Linfócitos B/efeitos dos fármacos , Linfócitos B/enzimologia , Linfócitos B/imunologia , Linfócitos B/patologia , Linhagem Celular Transformada , Consanguinidade , Análise Mutacional de DNA , Éxons , Feminino , Genótipo , Humanos , Lactente , Interleucina-2/farmacologia , Íntrons , Janus Quinase 3 , Masculino , Fenótipo , Fosforilação/efeitos dos fármacos , Estrutura Terciária de Proteína , Proteínas Tirosina Quinases/química , Imunodeficiência Combinada Severa/imunologiaRESUMO
During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3-gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T(-)B(+) SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families.
Assuntos
Mutação/genética , Proteínas Tirosina Quinases/deficiência , Proteínas Tirosina Quinases/genética , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/genética , Aconselhamento Genético , Humanos , Janus Quinase 3 , Modelos Moleculares , Polimorfismo Genético/genética , Conformação Proteica , Proteínas Tirosina Quinases/química , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/imunologiaRESUMO
Combined immune deficiencies comprise a spectrum of genetic disorders characterized by developmental or functional defects of both T and B lymphocytes. Recent progress in cell biology and molecular genetics has unraveled the pathophysiology of most of these defects. In particular, the most common form of severe combined immune deficiency in humans, with lack of circulating T cells, a normal or increased number of B lymphocytes, and an X-linked pattern of inheritance (SCIDXI) has been shown to be due to defects of the IL2RG gene, encoding for the common gamma chain (gammac), shared by several cytokine receptors. Furthermore, defects of the JAK3 gene, encoding for an intracellular tyrosine kinase required for signal transduction through gammac-containing cytokine receptors, have been identified in patients with autosomal recessive T-B+ SCID. Characterization of the functional properties of cytokines that signal through the gammac-JAK3 signaling pathway has been favored by the detailed analysis of SCID patients. Specifically, the key role of IL-7 in promoting T cell development has been substantiated by the identification of rare patients with T-B+ SCID who have a defect in the alpha subunit of the IL-7 receptor (IL7Ralpha). The heterogeneity of genetic defects along the same signaling pathway that may lead to combined immune deficiency is paralleled by the heterogeneity of immunological phenotypes that may associate with defects in the same gene, thus creating a need for detailed immunological and molecular investigations in order to dissect the spectrum of combined immune deficiencies in humans.
Assuntos
Proteínas Tirosina Quinases/imunologia , Receptores de Interleucina-7/imunologia , Imunodeficiência Combinada Severa/imunologia , Transdução de Sinais , Animais , Citocinas/imunologia , Humanos , Imunofenotipagem , Subunidade gama Comum de Receptores de Interleucina , Janus Quinase 3 , Modelos Imunológicos , Receptores de Citocinas/imunologiaRESUMO
Human cytomegalovirus (HCMV), a human herpesvirus, is the leading viral cause of birth defects (1,2). In acquired immune deficiency syndrome (AIDS) patients, HCMV can cause severely debilitating colitis and retinitis; it is now an increasingly common cause of life-threatening pneumonitis in transplant patients (3-5). HCMV has a severely restricted host range in culture. It grows efficiently only in primary human diploid fibroblasts (HFF) and a few selected human cell lines (6-9). Monocytes serve as a major reservoir of latent HCMV in humans and HCMV can be grown in vitro in primary monocyte-derived macrophages (M/M) (10-14).
RESUMO
The need for a rotavirus vaccine in any particular country depends primarily on the number of hospitalized cases. Since only limited data are available for Germany, we undertook a retrospective hospital-based analysis in order to gather further information. From 1987 through 1996, a total of 3618 inpatients were hospitalized with a diagnosis of gastroenteritis (ICD 9). In 892 (25%) of them the causative organism was a rotavirus. During the same period, 1886 (out of 8383; 22%) stool specimens tested in the hospital laboratory were obtained from rotavirus-positive inpatients. In 49.2% the infection was community-acquired, and in the remainder of nosocomial origin. Infants under 4 months of age (n = 709: 38%) predominated among both the nosocomial and community-acquired infections. Premature neonates made up 26% of the nosocomial, but only 2% of the community-acquired cases of diarrhoea. The winter peak (January) was most pronounced in the age group 4-12 months, but in those more than 1 y old the peak came a month later. The median hospitalization time for community-acquired cases was 4 d (mean 5.9 d). The mortality was 0.1%. Rotavirus infection must therefore be regarded as a considerable burden, particularly with regard to infants and young children. Furthermore, the morbidity due to nosocomial infection with the rotavirus, analysed here in a long-term observational study, is unexpectedly high.
Assuntos
Infecção Hospitalar/epidemiologia , Infecções por Rotavirus/epidemiologia , Pré-Escolar , Infecções Comunitárias Adquiridas/epidemiologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/virologia , Alemanha/epidemiologia , Hospitalização , Humanos , Lactente , Masculino , Estudos Retrospectivos , Estações do AnoRESUMO
BACKGROUND: Croup normally is characterized by acute onset and a self limited course of only few days. In 1990 and 1991 at the University Children's Hospital Freiburg an unexpected high number of patients were hospitalized for prolonged Croup syndrome. Expanded microbiological investigations were used to uncover etiologic factors. METHODS: Of a total of 138 inpatients with Croup 60 (17 in their first year of life, 21 in the second year of life and 22 infants older than 2 years) had bacteriological (37 nasopharyngeal-, 4 tracheal-aspirates or 19 throat swabs), and virological (antigen detection in nasopharyngeal aspirates, n = 28) tests. Of these patients 48% were hospitalized longer than 3 days (mean 4,7; range 1-18 days). RESULTS: Bacteria found: B. catarrhalis 24/11 (total/pure-culture), S. pneumoniae 15/6, H. influenzae 10/3, S. group A 5/4 and S. aureus 4/1. Sixteen specimen yielded more than one pathogen, one specimen was sterile. Nasopharyngeal secretions had the most reliable results: Pure cultures (72%) and associations of two pathogens (87%) were found in these aspirates, and only 26% of the unspecific mixed findings (p < 0.005; chi 2-Test). Of the patients hospitalized longer than 3 days 27.6% had positive cultures for H. influenzae, whereas only 6.5% of those hospitalized shorter (p < 0.05; chi 2-Test). The only microorganism with an age-bound distribution was B. catarrhalis found predominantly (54.2%) in the 2nd year of life, with 62% of patients positive (p < 0.05; chi 2-Test). Virus found: RSV (n = 3), Parainfluenza 2 (1) and Parainfluenza 3 (1). CONCLUSIONS: Nasopharyngeal aspirate is the most reliable specimen for a bacteriologic diagnosis in Croup. In the second year of life B. catarrhalis is present in most Croup cases, and H. influenzae was associated with a prolonged course of the disease. An appropriate antibiotic therapy therefore must cover these two pathogens.
Assuntos
Infecções Bacterianas/microbiologia , Crupe/microbiologia , Viroses/microbiologia , Anticorpos Antivirais/análise , Infecções Bacterianas/terapia , Técnicas Bacteriológicas , Pré-Escolar , Crupe/terapia , Feminino , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/terapia , Haemophilus influenzae , Humanos , Lactente , Tempo de Internação , Masculino , Moraxella catarrhalis , Nasofaringe/microbiologia , Paramyxoviridae , Vírus Sinciciais Respiratórios , Viroses/terapiaRESUMO
During the course of a 3-year epidemic of respiratory syncytial virus (RSV) in an Neonatal Intensive Care Unit, we examined premature neonates for the clinical features of RSV infections and the risk factors predisposing towards transmission of the disease. Seventy-nine infants with a median gestational age of 31 weeks were tested in 113 episodes of clinical deterioration for the presence of RSV antigen in nasopharyngeal secretions. Forty-seven results were positive and 66 negative. Bradycardia, which is gestational-age dependent, was the main presenting clinical symptom of an RSV infection in 75% of cases. The probability of an RSV-positive result in an episode with bradycardia, hypercapnia and fever was calculated to be 0.75. The only identifiable epidemiological risk factor was the total number of symptomatic RSV-infected infants in the ward. CONCLUSION. Bradycardia may indicate the presence of an RSV infection: the appropriate tests should be carried out and infection control reinforced immediately.
Assuntos
Doenças do Prematuro/fisiopatologia , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Antígenos Virais/análise , Bradicardia/etiologia , Infecção Hospitalar/prevenção & controle , Feminino , Idade Gestacional , Humanos , Hipercapnia/etiologia , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Infecções por Vírus Respiratório Sincicial/transmissão , Vírus Sinciciais Respiratórios/imunologia , Fatores de RiscoRESUMO
BACKGROUND: Since isolation of the Rotavirus (RV), there is rapidly growing concern about the possible involvement of RV in Central Nervous System (CNS) disorders, especially in Japan. We looked for symptomatic CNS involvement in a large series of RV infections and it's possible risk factors in a European setting. METHODS: Two-year retrospective survey based at the University Children's Hospital of Freiburg, Germany, a secondary and tertiary care centre with a urban and rural catchment area of 400,000 people. First, the case records of all 366 inpatients aged under two years excreting RV were searched for signs and symptoms of CNS involvement. Second, records of all 32 patients hospitalised with meningitis/encephalitis during the study period were checked for evidence of RV infection. RESULTS: In 15 of 366 children signs of CNS involvement (seizures, meningeal and encephalitic signs) were found. They were older (p = 0.023), had higher temperatures (p = 0.001) and CRP values (p = 0.019). Five of the fifteen had underlying neurological diseases, two had an additional salmonella infection and one suffered from hypernatraemic toxicosis. In the remaining seven children, higher temperature (p = 0.037) and older age (p = 0.05) remained significant risk factors. CNS-signs occurred in 2% of RV-excreting children, a rate equal to the prevalence of febrile seizures among all inpatients during the study period (2.2%). Of all 32 patients hospitalised with a diagnosis of meningitis or encephalitis only four had their stools tested for RV, all with a negative result. CONCLUSIONS: CNS symptoms in children aged less than two years with rotavirus diarrhoea have the same clinical epidemiology as febrile seizures and thus, in general, don't need additional diagnostic procedures.
Assuntos
Infecções do Sistema Nervoso Central/diagnóstico , Hipernatremia/etiologia , Infecções por Rotavirus/diagnóstico , Rotavirus/isolamento & purificação , Convulsões Febris/etiologia , Infecções do Sistema Nervoso Central/complicações , Encefalite/complicações , Encefalite/diagnóstico , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Meningite/complicações , Meningite/diagnóstico , Estudos Retrospectivos , Rotavirus/patogenicidade , Infecções por Rotavirus/complicações , Convulsões Febris/epidemiologia , Resultado do TratamentoRESUMO
In a prospective clinical study, rates of isolation of Moraxella catarrhalis in nasopharyngeal aspirates from 122 children with respiratory tract infection and 72 healthy controls were compared. In the patient group, Moraxella catarrhalis and Streptococcus pneumoniae were the most frequently isolated pathogens (38% and 42%, respectively). Monocultures of each pathogen were equally distributed in patients and controls (41% and 42%), whereas mixed infections were found more frequently in the patient group (42% vs 14%; normal flora, 17% vs 44%). Moraxella catarrhalis appears to be a relevant respiratory pathogen. The isolation of two or more pathogens in nasopharyngeal aspirates seems to be as indicative of relevant infection as is monoculture.
Assuntos
Moraxella catarrhalis/isolamento & purificação , Infecções por Neisseriaceae/microbiologia , Infecções Respiratórias/microbiologia , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Moraxella catarrhalis/efeitos dos fármacos , Estudos ProspectivosRESUMO
Extraintestinal manifestations of salmonellosis in paediatric patients are found predominantly in infants less than three months of age. Genital involvement is a rare complication. We present a short review of the literature and describe the case of a 10-week-old boy suffering from severe diarrhoea, who presented with a swelling of the right testicle after six days of illness. He underwent surgery on suspicion of testicular torsion, whereby orchitis was diagnosed. Salmonella enteritidis was cultured from the intraoperative swab. All cultures from blood, CSF and urine remained sterile. We conclude that orchitis must be taken into consideration as an extraintestinal complication of enteric salmonellosis and as a differential diagnosis of testicular torsion. In addition, we wish to emphasize that any infant less than three months of age with suspected or proven salmonellosis, should receive early antibiotic treatment.
Assuntos
Orquite/diagnóstico , Orquite/microbiologia , Infecções por Salmonella/diagnóstico , Salmonella enteritidis , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Humanos , Lactente , Masculino , Orquite/tratamento farmacológico , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/cirurgiaRESUMO
UNLABELLED: Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants. Since epidemiological data from Germany are scarce, a large retrospective hospital based analysis was performed. In the first part of the study, laboratory records were checked for RSV positive specimens from January 1988 to December 1997. A total of 1664 specimens were positive corresponding to 1171 episodes in 1064 patients; 88% were up to 4 years old and 47% up to 3 months old. The percentage of premature newborns from all patients 0-4 years old was 24%. The rate of nosocomial infection was 38%. The core RSV season began in December, lasted until April, and peaked in January and February. In the second part of the study, from April 1, 1997 to March 31, 1999, which encompassed two RSV winter seasons, patients with the ICD-9 coded discharge diagnoses of lower respiratory tract infections, bronchopulmonary dysplasia (BPD) and prematurity were analysed. Of the premature newborns, 25% were tested RSV positive at least once up to the age of 1 year, as were 52% of those with BPD. The rehospitalisation rate due to RSV infection was 22% in patients with BPD, and 8.9% in all premature newborns. Of patients with community acquired RSV infection, 12% required intensive care and 6% had to be ventilated mechanically. The mortality rates in both parts of the study were 0.8% and 0.7%, respectively. CONCLUSION: Respiratory syncytial virus infection in young children is also of major importance in Germany. Although the mortality rate is low, the high incidence and the severity of the disease in the particular risk group of premature infants with chronic lung disease contribute to a very high disease burden.
Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Pré-Escolar , Alemanha/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Infecções por Vírus Respiratório Sincicial/mortalidade , Vírus Sinciciais Respiratórios/isolamento & purificação , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
MxA protein--a stable product of cells stimulated by type I interferons--was examined prospectively for its ability to discriminate between viral and bacterial respiratory tract infections (RTIs) in 182 infants and children. The nasopharyngeal secretions (NPSs) of all of them were tested for MxA using enzyme-linked immunosorbent assay (ELISA), and the whole blood of 92. Seventy-three children undergoing elective surgery served as controls. These apparently healthy children had higher levels of serum MxA than adult controls. Using antigen detection and serology, a viral aetiology was diagnosed in 81/182 cases. The sensitivity and specificity of MxA ELISA were assessed at 92 and 76% for the blood test and at 40 and 91% for the NPS, respectively. The positive predictive value for a viral RTI was superior to a leucocyte count or C-reactive protein when determined only once.
Assuntos
Proteínas Sanguíneas/análise , Interferon Tipo I/sangue , Infecções por Vírus Respiratório Sincicial/sangue , Infecções por Vírus Respiratório Sincicial/virologia , Rotavirus/isolamento & purificação , Adulto , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Lactente , Contagem de Leucócitos , Nasofaringe/metabolismo , Projetos Piloto , Estudos ProspectivosRESUMO
Between 1985 and 1995, 1037 bacteremic episodes were recorded in a pediatric tertiary care center and analyzed retrospectively. Gram-positive bacteria accounted for 719 episodes (68%), gram-negative bacteria for 303 (29%), fungi for 16 (2%), and anaerobes for 12 (1%). In 526 (51%) patients, primarily neonates and oncology patients, a predisposing condition was present. In 390 (38%) episodes a clinical source of infection was documented. Mortality was highest in Pseudomonas bacteremia (45%). Since the bacterial spectrum differed widely between patient groups, the choice of empirical antimicrobial therapy should be based on any underlying condition present in the patient and the clinical source of infection. As anaerobes were rarely isolated. the routine use of anaerobic blood cultures in patients without predisposing conditions does not seem warranted.
Assuntos
Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Antibacterianos/farmacologia , Sangue/microbiologia , Causalidade , Criança , Pré-Escolar , Meios de Cultura , Suscetibilidade a Doenças , Fungemia/epidemiologia , Fungemia/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hospitais Pediátricos , Humanos , Imunocompetência , Hospedeiro Imunocomprometido , Lactente , Recém-Nascido , Testes de Sensibilidade Microbiana , Estudos RetrospectivosRESUMO
Transient complementation of human cytomegalovirus (HCMV) oriLyt DNA replication in permissive human diploid cells expressing replication genes under native promoters requires its UL36-38 gene products. Two of the immediate early (IE) proteins encoded by this locus, pUL37x1 and, to a lesser extent, gpUL37, activated expression of HCMV early gene promoter constructions. The other IE protein encoded by the UL36-38 locus, pUL36, and the early product, pUL38, did not transactivate the HCMV early promoter constructions under similar conditions. The acidic domain, common to both pUL37x1 and gpUL37, is required for activation of HCMV early promoter constructions. Conversely, gpUL37 sequences downstream of amino acid 199 are not required for transactivation of viral early promoters. Taken together, these results suggest that the requirement for UL36-38 products for HCMV DNA replication results, at least in part, from the requirement of the transactivation of HCMV early DNA replication promoters by pUL37x1 and, to a lesser extent, by gpUL37 and that the acidic domain is critical for this activity.
Assuntos
Citomegalovirus/genética , Replicação do DNA , DNA Viral , Regiões Promotoras Genéticas , Ativação Transcricional , Proteínas Estruturais Virais/fisiologia , Replicação Viral , Sítios de Ligação , Citomegalovirus/fisiologia , Proteínas de Ligação a DNA/genética , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Estruturais Virais/genéticaRESUMO
The JAK3 gene, encoding a tyrosine kinase functionally coupled to cytokine receptors which share the common gamma chain, has been identified as the defective gene for autosomal recessive severe combined immunodeficiency (SCID). Thus, specific mutational diagnosis has become possible. We screened all exons with a combined single strand conformational polymorphism and hetero-duplex formation assay followed by sequence analysis to identify specific mutations in two families. This assay was used on chorionic villus sampling derived DNA in two fetuses from two unrelated families, where we found mutations in both parents. We were able to exclude the mutations in both fetuses by the 12th week of gestation. The described method for first-trimester prenatal diagnosis of autosomal recessive T-B+SCID provides a valid tool to aid in genetic counselling and possibly prenatal therapy in this disease.
Assuntos
Diagnóstico Pré-Natal , Proteínas Tirosina Quinases/deficiência , Proteínas Tirosina Quinases/genética , Imunodeficiência Combinada Severa/diagnóstico , Alelos , Amostra da Vilosidade Coriônica , DNA/análise , Análise Mutacional de DNA , Éxons , Feminino , Humanos , Janus Quinase 3 , Contagem de Linfócitos , Masculino , Linhagem , Polimorfismo Conformacional de Fita Simples , Gravidez , Análise de Sequência de DNA , Imunodeficiência Combinada Severa/enzimologia , Imunodeficiência Combinada Severa/genéticaRESUMO
Hereditary severe combined immunodeficiency (SCID) includes a heterogeneous group of diseases that profoundly affect both cellular and humoral immune responses and require treatment by bone marrow transplantation. Characterization of the cellular and molecular bases of SCID is essential to provide accurate genetic counseling and prenatal diagnosis, and it may offer the grounds for alternative forms of treatment. The Jak3 gene is mutated in most cases of autosomal recessive T(-)B(+) SCID in humans. Jak3 belongs to the family of intracellular Janus tyrosine kinases. It is physically and functionally coupled to the common gamma chain, gammac, shared by several cytokine receptors. We have established the JAK3base registry for disease and mutation information. In order to study the structural consequences of the Jak3 mutations, the structure of the human Jak3 kinase and pseudokinase domains was modeled. Residues involved in ATP and Mg(2+) binding were highly conserved in the kinase domain whereas the substrate binding region is somewhat different compared to other kinases. We have identified the first naturally occurring mutations disrupting the function of the human Jak3 kinase domain. The structural basis of all of the known Jak3 mutations reported so far is discussed based on the modeled structure. The model of the Jak3 protein also permits us to study Jak3 phosphorylation at the structural level and may thus serve in the design of novel immune suppressive drugs.