Blood Samples Of Children Research Articles

An epigenome-wide study of a needs-based family intervention for offspring of trauma-exposed mothers in Kosovo.

Maternal stress and trauma during pregnancy have been shown to influence cortisol levels and epigenetic patterns, including DNA methylation, in the offspring. This study aimed to determine whether a tailor-made family intervention could help reduce cortisol levels in children born to traumatized mothers, and to determine whether it effected offspring DNA methylation. The secondary aim was to determine whether the family intervention influenced DNA methylation aging, a marker of biological aging. A needs-based family intervention was designed to help address relational difficulties and family functioning, and included a focus on family strengths and problem-solving patterns. Women survivors of sexual violence during the Kosovar war in 1998-1999, and their families (children with or without partners) were randomly assigned to 10 sessions of a family therapy over a 3-5-month period, or to a waitlist control group. Both mothers and children completed assessments prior to and after the intervention phase. Children's blood samples collected at these two time points were used to measure cortisol and epigenome-wide DNA methylation patterns (Illumina EPIC array). Cortisol levels, and genome-wide DNA methylation changes pre-/postintervention were compared between children in the intervention and the waitlist groups. DNA methylation age and accelerated biological aging were calculated. Sixty-two women-child dyads completed the study, 30 were assigned first to the intervention group, and 32 to the waitlist control group. In adjusted linear regression, the family intervention was associated with a significant decline in cortisol levels compared to the waitlist control (β=-124.72, 95% confidence interval [CI]: -197.4 to -52.1, p=.001). Children in the intervention group, compared to the waitlist control group, showed >1% differential methylation degree at 5819 CpG (5'-C-phosphate-G-3') sites across the genome (p<.01), with the largest methylation difference being 21%. However, none of these differences reached genome-wide significant levels. There was no significant difference in DNA methylation aging between the two groups. We find evidence that a tailored family-based intervention reduced stress levels in the children (based on cortisol levels), and modified DNA methylation levels at a number of sites across the genome. This study provides some preliminary evidence to suggest the potential for tailored interventions to help break the intergenerational transmission of trauma, however, large studies powered to detect associations at genome-wide significant levels are needed.

Severity of papular urticaria in children is associated with specific IgG4 anti-salivary gland antigens from Aedes aegypti.

Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.

Comparative Expression Analysis of Human Endogenous Retrovirus Elements in Blood Samples of Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a highly diverse group of developmental disorders with a multicausal etiology and a strong genetic basis. About 8% of the human genome consists of human endogenous retrovirus elements (HERVs). HERV transcription appears to be altered not only in specific brain regions but also in the peripheral blood of patients with psychiatric conditions such as schizophrenia, multiple sclerosis (MS), ASD, and different types of cancer. This study aims to investigate the blood-based expression of five distinct human endogenous retrovirus elements in a patient cohort of 31 children with Autism Spectrum Disorder (ASD) and a control group of 27 children with typical development. The comparative HERV expression analysis in 31 children with a diagnosis of ASD and 27 age- and sex-matched healthy controls was performed via a whole transcriptome sequencing approach combined with qRT-PCR analysis. Two HERV-encoded genes: HERV-P env, and HERV-R env, were found to be significantly downregulated in the group of children with ASD. Another HERV gene, HERV-W pol appeared to be significantly upregulated. Receiver operating characteristic (ROC) analysis indicated that the observed changes in transcript levels of HERV-P env and HERV-R env can discriminate between ASD patients and healthy controls with considerable sensitivity and specificity. Our results alongside a large number of expression studies conducted by other researchers suggest that human endogenous retrovirus elements may participate in important physiological processes and serve as key factors and markers for many conditions including ASD.

Molecular Detection of Extensively Drug-Resistant Salmonella Typhi and Carbapenem-Resistant Pathogens in Pediatric Septicemia Patients in Pakistan – a Public Health Concern

Aim: To determine the prevalence of multidrug (MDR) and extensively drug-resistant (XDR) pathogens from pediatric blood samples Methods: In total, 4543 children's blood samples were processed in the BacT/ALERT system. Confirmation of the isolates and MIC was determined in VITEK®2system. Molecular identification of blaIMP, blaVIM and blaOXA-48 was done by PCR. Results: Of 4543 blood cultures, 458 (10%) were positive for bacterial growth and SalmonellaTyphi (415; 90%) remained the primary pathogens. Antibiogram revealed 208 (50.1%) and 137 (33%) were MDR and XDR S. Typhi, respectively. Klebsiella pneumoniae displayed 46% resistance to imipenem. One hundred twelve (81.7%) XDR Typhi were positive for blaCTXM, whereas 14 (66.6%) blaVIM were found in carbapenem-resistant bacteria. Conclusion:A high prevalence of MDR and XDR pathogenswas found in peads blood culture.

Inhibitors of nitric oxide synthase can reduce extracellular traps from neutrophils in asthmatic children in vitro.

This study aimed to explore the link between neutrophil extracellular traps (NETs) and childhood asthma, to investigate the ability of nitric oxide (NO) to induce NETs in asthmatic children and find inhibitors to reduce NETs in the NO synthesis pathway. A total of 49 children with mild persistent asthma were included in the study and 20 healthy children's blood samples were collected as healthy controls. Children with asthma were divided into symptomatic and asymptomatic groups according to the presence or absence of symptoms on the day of blood collection. Neutrophils in peripheral blood were isolated and plasma was preserved. NO donor (sodium nitroferricyanide(III) dehydrate [SNP]) could provide NO and proved by a fluorescent probe. A PicoGreen Kit was used to detect the NETs quantificationally. Fluorescence microscopy prepared to observe the main structures of NETs. We measured NETs components (extracellular free double-stranded DNA [dsDNA]) in healthy, symptomatic and asymptomatic groups' plasma samples, and we compared the ability of SNP with phosphate-buffered saline, lipopolysaccharides (LPS), and phorbol 12-myristate 13-acetate (PMA) to induce NETs. NO synthase (NOS) inhibitors were added to see the impact on NETs formation. Plasma was obtained from all blood samples of 69 children. The neutrophils of 40 asthmatic and 20 healthy children were successfully obtained, the recovery rate was over 95%, and the cell activity was over 80%. There was higher extracellular free dsDNA in the plasma of symptomatic group (n = 27) than asymptomatic group (n = 22) and healthy group (n = 20; P < .05). Studies on neutrophils from 40 children with asthma found that NO can be produced by adding SNP, PMA, and LPS. SNP could induce NETs with dose- and time-dependent. PMA (160 nM) had the strongest ability to induce NETs, LPS (200 ng/mL) followed, SNP (200 µM) was the weakest (P < .05), and the amount of NETs in the asthma group was significantly higher than that in the healthy group (P < .05). NOS inhibitors had the same blocking capacity for PMA- and LPS-induced NETs (P > .05), while NG-nitro- l-arginine methyl ester (500 µM) had the strongest inhibitory effect on SNP induction with time-dependent (P < .05). Inducible NOS was found in the NETs structure. Children with asthma had higher levels of NETs in peripheral blood, especially when they had asthma symptoms. We verified the ability of NO to induce NETs, and found neutrophils from asthmatic children can produce more NETs in vitro. NOS inhibitors blocked this process may provide new therapeutic targets for childhood asthma.

The effect of distraction (Balloon Inflating) on pain level during the venous blood sampling in Children

Background: Every day a large number of children are subject to measures for prevention, diagnosis, and treatment of disease that most of these measures are associated with venous blood sampling. Painful measures such as blood sampling in children in addition to the physical and emotional annoying effect could cause wider negative consequences on childhood age and physical, behavioral and social disorders in children. This study aimed to determine the effect of distraction by inflating a balloon on the amount of pain during taking blood samples from children between the ages of 4 to 7. Methods: The study was an intervention clinical trial that was conducted on 80 children admitted to the pediatric department of Imam Khomeini Hospital in Jiroft- Kerman province and had the inclusion criteria after obtaining their parent&#039;s consent. Children were randomly grouped into the test (n = 40) and control (n = 40) groups that in the test group children&#039;s pain was measured during the venous blood sampling during inflating a balloon and their pain was measured in the control group without any intervention during blood sampling. Wong-Baker FACES questionnaire was used for pain assessment. Results: The results showed that the majority of participants were 4-7-year-old girls (60 percent). Average pain scores for children in the two groups showed no significant difference before the intervention but the average pain scores after the intervention in the test and control group were 1.38±2.56 and 4.2±1.58; there was a significant difference between pain in both test and control groups after the intervention (p-value &lt; 0.05). Conclusion: Using the method of distraction by inflating the balloon during venous blood sampling reduces pain in children.

Will the Real Coeliac Disease Please Stand Up? Coeliac Disease Prevalence in the German LIFE Child Study

Assessing the seroprevalence and the prevalence of definite coeliac disease (CD) in the German LIFE Child Health study cohort including immunoglobulin A (IgA) antibodies against tissue transglutaminase (IgA-TTG) in addition to IgG antibodies against deamidated gliadin peptides (IgG-DGP) and human leukocyte antigen (HLA)-DQ2/8 genotyping. Samples from children and adolescents were first screened for IgA-TTG and IgG-DGP. If IgA-TTG was above 0.5 times the upper limit of normal and/or IgG-DGP was positive, IgA antibodies against endomysium (IgA-EmA) were measured, and HLA was genotyped. In patients with only IgG-DGP positivity, total IgA was assayed. Subjects with suspicious results were followed up serologically and, in case of repeatedly positive antibody results, invited for a personal interview. Further diagnostic data were obtained independent from our study. We screened 2363 children's blood samples collected from 2011 to 2015. The seroprevalence, that is, IgA-TTG and/or IgA-EmA positivity or IgG-DGP positivity with IgA <0.05 g/L, was 1.57% (95% confidence interval [CI95%] 1.14-2.15). The prevalence of suspected CD, that is, seroprevalence and compatible HLA genotype with hitherto unknown mucosal damage, was 1.35% (CI95% 0.96-1.91). Definite CD, that is, seropositivity accompanied by positive intestinal biopsy or IgA-TTG ≥ 10 × upper limit of normal, was found in 0.42% (CI95% 0.22-0.80). Seven children claimed to have CD. The HLA haplotype, however, matched in only 4 of them resulting in an overall CD prevalence of at least 0.59% (CI95% 0.34-1.02). Thirteen unclear cases remained; therefore, the prevalence may even be higher. The prevalence of definite CD in a population-representative German cohort is higher than previously described. HLA-DQ typing is helpful to identify false-positive IgA-TTG patients negative for IgA-EmA and/or IgG-DGP under screening conditions and unmasks possible misdiagnoses of CD.

Concentrations of Environmental Chemicals in Urine and Blood Samples of Children from San Luis Potosí, Mexico.

Human biomonitoring (HBM) is an appreciated tool used to evaluate human exposure to environmental, occupational or lifestyle chemicals. Therefore, the aim of this study was to evaluate the exposure levels for environmental chemicals in urine and blood samples of children from San Luis Potosí, Mexico (SLP). This study identifies environmental chemicals of concern such as: arsenic (45.0 ± 15.0µg/g creatinine), lead (5.40 ± 2.80µg/dL), t,t-muconic acid (266 ± 220µg/g creatinine), 1-hydroxypyrene (0.25 ± 0.15µmol/mol creatinine), PBDEs (28.0 ± 15.0ng/g lipid), and PCBs (33.0 ± 16.0ng/g lipid). On the other hand, low mercury (1.25 ± 1.00µg/L), hippuric acid (0.38 ± 0.15µg/g creatinine) and total DDT (130 ± 35ng/g lipid) exposure levels were found. This preliminary study showed the tool's utility, as the general findings revealed chemicals of concern. Moreover, this screening exhibited the need for HBM in the general population of SLP.

Indoor Aeroallergens in Asthmatic Pediatric Population in Annaba (Algeria)

ABSTRACTThe aim of the present study is to highlight the kind of indoor aeroallergens and assess their role in asthma severity in children from Annaba city (Algeria). Our study concerned 68 asthmatic children and 50 healthy children. All children's blood samples were obtained to determine biological parameters, followed by home visit to these children to assess meteorological parameters and fungal exposure. It was found that the asthma severity was associated with eosinophilia (χ2, p = 0.01), rate of total IgE (χ2, p < 0.001) and sensitization to indoor aeroallergens. This association between the severity of the disease and sensitization was strengthened with the presence of mites (χ2, p < 0.01) and pets, namely cats (p < 0.001). Moreover, all houses of asthmatic children contain fungal spores, which were also associated with the sensitization to fungi (χ2, p < 0.001). The average indoor temperature and humidity in the houses of asthmatic children represent favorable conditions for the growth of mold and development of mites, whose presence, especially Cladosporium and Alternaria, was associated with sensitization to fungi and severity of asthma. The strongest sensitization was found with dust mites (Dermatophagoides pteronyssinus, Der p1 (d1) and Dermatophagoides farinae, Der f2 (d2)) which is closely associated with asthma severity.

Household Food Insecurity, Mother's Feeding Practices, and the Early Childhood's Iron Status.

Background:Health consequences of food insecurity among infants and toddlers have not been fully examined. The purpose of this study was to assess the relationship between household food insecurity, mother's infant feeding practices and iron status of 6–24 months children.Methods:In this cross-sectional study, 423 mother-child pairs were randomly selected by multistage sampling method. Children blood samples were analyzed for hemoglobin and serum ferritin concentrations. Household food security was evaluated using a validated Household Food Insecurity Access Scale. The mother's feeding practices were evaluated using Infant and Young Child Feeding practice variables including: The duration of breastfeeding and the time of introducing of complementary feeding.Results:Based on the results, of the studied households only 47.7% were food secure. Mild and moderate-severe household food insecurity was 39.5% and 12.8%, respectively. Anemia, iron deficiency (ID), and iron deficiency anemia were seen in 29.1%, 12.2%, and 4.8% of children, respectively. There was no significant association between household food insecurity; mother's feeding practices and child ID with or without anemia.Conclusions:We found no association between household food insecurity and the occurrence of anemia in the 6–24 months children. However, these findings do not rule out the possibility of other micronutrient deficiencies among the food-insecure household children.

Repetitive genomic elements and overall DNA methylation changes in acute myeloid and childhood B-cell lymphoblastic leukemia patients.

Aberrant epigenetic regulation is a hallmark of neoplastic cells. Increased DNA methylation of individual genes' promoter regions and decreases in overall DNA methylation level are both generally observed in cancer. In solid tumors, this global DNA hypomethylation is related to reduced methylation of repeated DNA elements (REs) and contributes to genome instability. The aim of the present study was to assess methylation level of LINE-1 and ALU REs and total 5-methylcytosine (5metC) content in adult acute myeloid leukemia (AML) (n = 58), childhood B-cell acute lymphoblastic leukemia (ALL) (n = 32), as the most frequent acute leukemias in two age categories and in normal adult bone marrow and children's blood samples. DNA pyrosequencing and ELISA assays were used, respectively. Global DNA hypomethylation was not observed in leukemia patients. Results revealed higher DNA methylation of LINE-1 in AML and ALL samples compared to corresponding normal controls. Elevated methylation of ALU and overall 5metC level were also observed in B-cell ALL patients. Differences of REs and global DNA methylation between AML cytogenetic-risk groups were observed, with the lowest methylation levels in intermediate-risk/cytogenetically normal patients. B-cell ALL is characterized by the highest DNA methylation level compared to AML and controls and overall DNA methylation is correlated with leukocyte count.

Correlations of PCBs, DIOXIN, and PBDE with TSH in Children's Blood in Areas of Computer E-waste Recycling

Objective To study correlations of polychlorinated biphenyls (PCBs), DIOXIN, and polybrominated diphenyl ethers (PBDE) with thyroid stimulating hormone(TSH) in children, and assess the impact on children's health. Methods Three hundred and sixty nine children aged from 6 to 8, including 195 from Luqiao, the computer E-waste recycling area, and 174 from Longyou, the control area, were selected for this investigation to elucidate the correlation of PCBs, DIOXIN, and PBDE with TSH in children's blood samples. The children had a physical examination and their blood levels of PCBs, DIOXIN, PBDE, and TSH were detected after sample collection. Results In the E-waste recycling area, the contents of PCBs, PBDE, DIOXIN, and TSH in the blood samples of children were 484.00±84.86 ng·g −1 lipid weight, 664.28±262.38 ng·g −1 lipid weight, 26.00±19.58 ng·g −1 lipid weight and 1.88±0.42 μIU/mL (serum) respectively, while in the control area, the PCBs, PBDE, DIOXIN, and TSH contents were 255.38±95 ng·g −1 lipid weight, 375.81±262.43 ng·g −1 lipid weight, 39.64±31.86 ng·g −1 lipid weight, and 3.31±1.04 μIU/mL respectively. Conclusion The health status of children in the control area are better than that in the contaminated area. Among children who are exposed to persistent organic pollutants, the pollutant content increases significantly in their serum, and the distribution of TSH levels in their bodies are also affected.

Maturation of cytokine‐producing capacity from birth to 1 yr of age

Little is known about the immunologic maturation in the early stages of life. The aim of this study was to investigate maturation of immune system from birth to 1 yr of age and to compare immune functions between mothers and their children. Also the effect of atopy to the immune responses of children was examined. Cord blood samples (n = 228) and peripheral blood samples of children (n = 200) and their mothers (n = 208) 1 yr after birth were collected. Whole blood samples were stimulated for 24 and 48 h with Staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and the combination of phorbol ester and ionomycin (P/I). Production of TNF-alpha, IFN-gamma, IL-5, IL-8 and IL-10 was determined using ELISA. Significant mother-to-child correlation was detected in cytokine-producing capacity at the age of 1 yr. TNF-alpha (P/I, SEB and LPS stimulation), IFN-gamma (P/I and SEB), IL-5 (P/I and SEB) and IL-10 (P/I, SEB and LPS) producing capacity increased from birth to 1 yr of age. In general, stimulated cytokine responses were higher in mothers' than in children's blood samples, except in the case of P/I and LPS-stimulated IL-8, which were highest at birth. Maternal inhalation atopy was associated with increased cord blood IL-5 (24 and 48 h) and IL-10 (48 h) production following P/I stimulation. Also children of food atopic mothers expressed elevated cord blood IL-10 (48 h, P/I) responses and decreased IFN-gamma/IL-5 ratio (24 h, P/I). In addition, the production of IFN-gamma (24 and 48 h, P/I) and the IFN-gamma/IL-5 ratio (24 h and 48 h, P/I) at the age of 1 yr was lower among children with food atopic mothers. In conclusion, our results suggest that both adaptive and innate immune responses increase from birth to 1 yr of age, but are still weak in comparison to adult responses. Cytokine responses of children begin to correlate with those of their mothers during the first year of life. Although only few associations were observed between atopy and cytokine-producing capacity, our results suggest that children of atopic mothers express T(h)2-polarized cytokine pattern.

Un cas d’encéphalopathie acquise de l’enfant. À propos d’une cause que l’on croyait disparue

Subacute central nervous system infection must be considered in any infant presenting with progressive encephalopathy. We present the case of an 18-month-old child with normal neuromotor development until the age of 14 months admitted for spastic hypertonia of the legs and arms associated with axial hypotonia. The mother reported that she recently had been found to be HIV-seropositive. HIV antibodies were negative during the first trimester of pregnancy. On the child's blood sample, the HIV test was positive associated with a major decrease in CD4 cell count. Viral load (ARN-PCR) was 720 copies par millilitre. On brain MRI, hypersignals were found in the white matter. HIV related encephalopathy caused by maternal fetal transmission was diagnosed. After 2 months of antiretroviral treatment (azidothymidine, lamivudine, and boosted lopinavir), the child's neurological condition improved. HIV infection must be suspected in all infants with progressive encephalopathy. The HIV test in pregnant women must be proposed at the beginning of pregnancy and repeated during the last trimester.

Association of Family Stress With Natural Killer Cell Activity and the Frequency of Illnesses in Children

To examine prospective associations between chronic stress in the parent-child and family systems and subsequent rates of illnesses and the activity of natural killer (NK) cells in children. Prospective cohort study. The Golisano Children's Hospital at Strong, Rochester, NY, from July 1, 2001, to June 30, 2003. One hundred sixty-nine socioeconomically and racially diverse children (aged 5-10 years) and their parents. Parents completed measures of their psychiatric symptoms and stress in the family every 6 months. Children's blood samples were obtained for NK cytotoxicity assays every 6 months. Parent-reported total child illnesses and febrile illnesses and results of NK cell cytotoxicity assays. We estimated adjusted illness rate ratios and adjusted mean differences in NK activity. Elevated parental psychiatric symptoms occurring with family stressors were associated with more total illnesses (rate ratio, 1.11; 95% confidence interval [CI], 1.00-1.22) and febrile illnesses (rate ratio, 1.36; 95% CI, 1.13-1.64) in children. Natural killer cell function was enhanced in children whose parents reported more chronic stress (estimate, 0.15; 95% CI, 0.05-0.26). Natural killer cell function was not associated with short-term changes in stress. Stress-illness relationships were not associated with stress-related alterations in NK cell function. Chronic family stress was associated with increased illnesses in children. Unlike older adults, children living with elevated chronic stress had enhanced rather than decreased NK cytotoxicity, suggesting chronic stress may have different effects on the developing immune system. Impaired parental functioning may be a mechanism linking family stress with adverse effects on children's health.

Infecção pelo vírus linfotrópico de células T humanas e transmissão vertical em gestantes de estado da Região Centro-Oeste do Brasil

OBJETIVOS: avaliar a prevalência, características epidemiológicas (idade e procedência) e a taxa de transmissão vertical da infecção pelo HTLV I/II em gestantes submetidas à triagem pré-natal de acordo com o Programa de Proteção à Gestante do Estado de Mato Grosso do Sul. MÉTODOS: estudo descritivo transversal que incluiu 32.512 gestantes submetidas à triagem pré-natal no período de novembro de 2002 a outubro de 2003. Todas as gestantes da amostra foram submetidas aos testes sorológicos pelo método ELISA para o diagnóstico da infecção pelo HTLV, sendo os casos positivos confirmados pelos métodos Western blot e/ou PCR. O diagnóstico neonatal de infecção congênita foi realizado pela pesquisa de anticorpos anti-HTLV I/II confirmados por Western blot e PCR. A relação entre as variáveis (idade e procedência) foi avaliada pelo teste do chi2, em tabelas de dupla entrada, considerando p<0,05 para rejeição das hipóteses de nulidade (não existência da associação entre a idade materna e infecção pelo HTLV I/II e associação entre procedência e positividade para a infecção pelo HTLV I/II.). RESULTADOS: encontrou-se prevalência de 0,1% de gestantes infectadas pelo HTLV I/II (37) dentre as 32.512 pacientes triadas. A média de idade das gestantes infectadas pelo HTLV foi de 25,4±6,4 anos, sendo que houve predomínio de pacientes procedentes do interior do estado (78,4%). Não houve associação da idade com faixa etária materna e procedência. Apenas 8 (21,6% da amostra) recém-nascidos foram avaliados quanto à presença da infecção congênita pelo HTLV I/II, todos com infecção congênita confirmada. Apenas 1 recém-nascido (9%) recebeu amamentação natural. CONCLUSÕES: a prevalência da infecção pelo HTLV I/II em gestantes sul-matogrossenses foi menor que os valores encontrados em estudos com gestantes de países endêmicos. No entanto, esteve próximo às taxas encontradas em países considerados não endêmicos e em alguns estudos brasileiros. A transmissão vertical ocorreu em 100% da amostra avaliada, mesmo a amamentação sendo proscrita. Verificou-se a necessidade de aprimorar o seguimento das gestantes e seus recém-nascidos no estado, uma vez que a minoria dos recém-nascidos foram investigados quanto à ocorrência de transmissão vertical do HTLV.

Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome

The pharmacokinetics and safety of HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 +/- 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 +/- 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 +/- 6.8 hours) and plasma concentration after infusion (30.7 +/- 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponential function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 +/- 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 +/- 0.02 L/kg) were different (p < 0.002) from values observed in children's blood samples during 36 hours. Within the pediatric population, no age-related differences in pharmacokinetics could be detected. Drug disposition was unaffected by renal or hepatic dysfunction. Decreased blood pressure was the most frequently reported adverse event; 4 (9%) episodes in 44 infusions were considered possibly related to the study drug. Gram-negative bacteremia was documented in 23 (55%) of 42 patients. The overall mortality rate was 31%. Enterobacter cloacae was the most common pathogen isolated. Haemophilus influenzae type b was isolated from one child with sepsis syndrome. We conclude that infusion of HA-1A in children is associated with a low incidence of side effects. The pharmacokinetic-pharmacodynamic behavior of HA-1A in children requires further study to determine whether developmental differences exist and how these differences might affect drug administration. Efficacy remains to be studied.

Computer programs for adapting two-dimensional gels to the study of mutation.

We are attempting to adapt the two-dimensional polyacrylamide gel technology to the search for mutations that after the electrophoretic mobility of proteins. These events are expected to have a frequency on the order of 10(-6). To this end, programs that run on the CytocomputerTM are being developed for comparing the pattern of the gel derived from a child's blood sample with those of the gels of corresponding samples from its parents. We anticipate examining thousands of such trios. Programs are described that perform background normalization, noise filtering, spot detection, gel registration, and, finally, compare the father/mother/child gel trios for the presence of unique protein moieties in the child that are consistent with a mutational event.