Hospital malnutrition and inflammatory response in critically ill children and adolescents admitted to a tertiary intensive care unit.

UNLABELLED: Critical illness has a major impact on the nutritional status of both children and adults. A retrospective study was conducted to evaluate the incidence of hospital malnutrition at a pediatric tertiary intensive care unit (PICU). Serum concentrations of IL-6 in subgroups of well-nourished and malnourished patients were also evaluated in an attempt to identify those with a potential nutritional risk. METHODS: A total of 1077 patients were enrolled. Nutritional status was evaluated by Z-score (weight for age). We compared mortality, sepsis incidence, and length of hospital stay for nourished and malnourished patients. We had a subgroup of 15 patients with severe malnutrition (MN) and another with 14 well-nourished patients (WN). Cytokine IL-6 determinations were performed by enzyme-linked immunosorbent assay. RESULTS: 53% of patients were classified with moderate or severe malnutrition. Similar amounts of C- reactive protein (CRP) were observed in WN and MN patients. Both groups were able to increase IL-6 concentrations in response to inflammatory systemic response and the levels followed a similar evolution during the study. However, the mean values of serum IL-6 were significantly different between WN and MN patients across time, throughout the study (p = 0.043). DISCUSSION: a considerable proportion of malnourished patients need specialized nutritional therapy during an intensive care unit (ICU) stay. Malnutrition in children remains largely unrecognized by healthcare workers on admission. CONCLUSIONS: The incidence of malnutrition was very high. Malnourished patients maintain the capacity to release inflammatory markers such as CRP and IL-6, which can be considered favorable for combating infections On the other hand, this capacity might also have a significant impact on nutritional status during hospitalization.

The effects of exposing rats to cigarette smoke on milk production and growth of offspring.

OBJECTIVES: To analyze the effects of exposure to cigarette smoke during gestation and lactation on the milk production of rats and on the weight gain and linear growth of their offspring. METHODS: Three groups of female rats were studied during gestation and lactation: 15 rats were exposed to cigarette smoke and air flow, 18 rats were handled, i.e., exposed to compressed air flow, and 18 rats were used as controls. Newborn rats were measured and weighed every 5 days, from the first to the 15th day. Milk production was estimated by 1-hour milk extraction and weight gained by litters. RESULTS: The offspring of rats exposed to cigarette smoke weighed less and were shorter at birth. During lactation, the offspring of rats exposed to smoke and also of rats that had merely been handled gained less weight than the control group. Milk production gauged by the 1-hour extraction method was reduced in the group exposed to smoke and, to a lesser extent, also in the group that had been handled. Milk production estimated according to the pups' weight gain was reduced equally in the groups exposed to smoke and merely handled, when compared to the control group. CONCLUSIONS: Exposure to cigarette smoke compromised the birth weight and birth length, but during lactation, handling also compromised weight gain of offspring. Handling and, to a greater extent, exposure to tobacco, were prejudicial to milk production.

Association of Parasite Load Levels in Amniotic Fluid With Clinical Outcome in Congenital Toxoplasmosis.

OBJECTIVE: To correlate neonatal and infant clinical outcome with parasite load in amniotic fluid (AF). METHODS: We conducted a retrospective cohort study of 122 children whose mothers had toxoplasmosis during pregnancy. The children were monitored from birth to 12 months old. Stored AF samples were obtained at maternal diagnosis and tested by quantitative polymerase chain reaction. Gestational age at maternal infection, quantitative polymerase chain reaction results, neonatal anti-Toxoplasma gondii immunoglobulin (Ig) M, and clinical outcome at 12 months were correlated. RESULTS: Maternal infection occurred in 18 of 122 (14.7%) and 104 of 122 (85.2%) women in the first and second trimesters, respectively. At birth, IgM was present in 107 of 122 (87.7%) neonates and 36 (29.5%) were symptomatic. Of these, half occurred in the first and the other half in the second trimester and 6 of 36 had severe infections (16.7% of symptomatic, 4.9% of total), all infected in the first trimester. Parasite load levels were highly variable (median 35 parasites/mL, range 2-30,473). Logistic regression correlated symptomatic infection with gestational age (odds ratio [OR] 0.47, CI 0.31-0.73) and parasite load (OR 2.04, CI 1.23-3.37), but not with positive IgM (OR 6.81, CI 0.86-53.9). Negative correlations were found between gestational age and parasite load (rs -0.780, CI -0.843 to -0.696), gestational age and symptoms (rs -0.664, CI -0.755 to -0.547), but not gestational age and IgM (rs -0.136, CI -0.311 to 0.048). Parasite load levels distributed by percentile showed that all symptomatic patients appeared from the 75th percentile and all severe infections from the 95th percentile. Load rankings showed doubled the OR for each 20 parasite/mL increment. Parasite load was associated with symptomatic infections (area under the curve 0.959, CI 0.908-0.987) as well as gestational age (area under the curve 0.918, CI 0.855-0.960) and both parameters combined (area under the curve 0.969, CI 0.920-0.992). CONCLUSION: Parasite load in AF is associated with the clinical outcome in congenital toxoplasmosis, irrespective of gestational age at maternal infection.

TNF-alpha and IL-6 in the diagnosis of bacterial and aseptic meningitis in children.

The objective of this study was to analyze the usefulness of tumor necrosis factor-alpha and interleukin-6 cerebrospinal fluid concentrations for the differential diagnosis between bacterial and aseptic meningitis in children and in the prognostic evaluation. A cross-sectional study was performed on 35 children between 1 month and 12 years of age with suspected meningitis. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. The Mann-Whitney test and Spearman's correlation coefficients were used for statistical analysis. Six children presented bacterial meningitis, 13 aseptic, and 16 had no meningitis. The tumor necrosis factor-alpha concentrations were significantly higher in the bacterial meningitis group as compared with the aseptic group (P = 0.001) and among groups with and without meningitis (P = 0.000). There was correlation between tumor necrosis factor-alpha and cerebrospinal fluid leukocytes (P = 0.019), protein (P = 0.000), and glucose (P = 0.038). There was no association between cytokines and complications of the meningitis. The tumor necrosis factor-alpha concentrations in the cerebrospinal fluid were useful markers for distinguishing bacterial from aseptic meningitis and were demonstrated to be useful in evaluating the intensity of the inflammatory process in the central nervous system.

[Interleukins 6 and C-reactive protein for the diagnosis of late onset sepsis in the newborn infant]. / Interleucina 6 e proteína c reativa no diagnóstico de sepse tardia no recém-nascido.

BACKGROUND: Verify the accuracy of interleukin 6 (IL-6) and C-reactive protein (CRP) for diagnosis of late onset sepsis in newborn (NB) infants. METHODS: a prospective cohort study with 43 NB infants hospitalized at the NICU with suspicion of late onset sepsis was carried out. Levels of IL-6 and of CRP were dosed with suspicion diagnoses; day (0) and sequentially on day 1, 3, and 7 of the evolution and the best cut-off values were calculated for the diagnoses. Indices of sensibility (S), specificity (SP), positive predictive value and negative predictive value (PPV, NPV) were calculated for each test as well as for the combination between them. RESULTS: Levels of IL-6 and CRP were above the established cut-off values in the NB infants with sepsis and with presumed sepsis. There was a significant difference between both groups, where the only difference was the positive blood culture for the first group. Diagnosis could be rejected in 6 NB infants. The IL-6 showed better indices on the day of suspicion diagnosis, day 0 (S: 88.9%, Sp: 80.0%, PPV: 76.2%, NPV: 90.9%), followed by the C-reactive protein (S: 94.0%, Sp: 78.3%, PPV: 77.3%, NPV: 94.7%) 24 hours later. The combination of IL-6 / CRP demonstrated to be adequate for early diagnosis of sepsis on day 0 and 24 hours later with S and NPV of 100%. CONCLUSION: for diagnosis of sepsis the combination interleukin 6 / CRP presented accuracy. During the following days their development reflected the clinical evolution of the NB infants.

The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance.

BACKGROUND: For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species. AIMS: In this study we investigated missense mutations in ERG11 genes of Candida albicans, Candida glabrata and Candida tropicalis isolates previously evaluated by susceptibility testing to fluconazole. METHODS: Screening for these mutations was performed on 19 Candida clinical isolates (eight C. albicans, five C. glabrata and six C. tropicalis) resistant and susceptible to fluconazole. The ERG11 gene was amplified by PCR with specific primers for each Candida species and analyzed by automated sequencing. RESULTS: We identified 14 different missense mutations, five of which had not been described previously. Among them, a new mutation L321F was identified in a fluconazole resistant C. albicans isolate and it was analyzed by a theoretical three-dimensional structure of the ERG11p. CONCLUSION: The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance.

Magnesium and intrauterine growth restriction.

BACKGROUND: The presence of intrauterine growth restriction (IUGR), could potentially lead to imbalances of Mg homeostasis, which have not yet been fully clarified. OBJECTIVE: To describe, in term newborn (NB) without IUGR, ionized magnesium (iMg) and total magnesium (TMg) concentrations in umbilical cord blood, on the third and seventh days of life and to compare these values with those of term NB with IUGR. METHODS: A prospective study was performed on 70 term NB divided into two groups: Group I-30 NB without IUGR and Group II-40 NB with IUGR. TMg concentrations were determined in sera by a classical colorimetric end point method (Cobas-Mira, Roche), and iMg was determined in whole blood by means of the Stat Profile-M analyzer (NOVA Biomedical). RESULTS: We found that in term NB without IUGR, TMg concentrations increased during the first week of life and were lower than those of NB with IUGR in cord blood (p < 0.05). NB without IUGR had decreased iMg concentrations in comparison to NB with IUGR in all sampling times, i.e., cord blood, third and seventh days of life (p < 0.001). iMg concentrations remained unchanged during the study period. We also found that all NB enrolled in the study presented with low iMg concentrations (reference interval 0.4-0.6 mmol/L). CONCLUSION: The presence of IUGR may influence neonatal levels of magnesium, suggesting an effect on the modulation of this ion homeostasis, during the perinatal period.

Serum soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha levels in children with celiac disease: response to treatment.

OBJECTIVES: T-cell mediated immune response to dietary gluten and cytokines release are important for the enteropathy seen in celiac disease. We investigated the serum levels of soluble interleukin-2 receptor, interleukin-6, and tumor necrosis factor-alpha in celiac children before and after gluten exclusion. METHODS: Cytokine levels were determined using enzyme immunoassay in serum from 12 untreated celiac patients, 16 treated celiac patients on a gluten-free diet for at least two years, and from 26 control children. Eight of 12 untreated patients were also investigated at 6 and 12 months after gluten exclusion. Serum IgA antiendomysium antibodies were also assayed by indirect immunofluorescence. RESULTS: Soluble interleukin-2 receptor and interleukin-6 levels were significantly increased in untreated celiac patients compared with treated and control children. There was no difference in the tumor necrosis factor-alpha levels between the groups. Soluble interleukin-2 receptor levels were the only ones significantly decreased at 12 months after gluten exclusion. However, soluble interleukin-2 receptor and interleukin-6 levels at 12 months were significantly higher compared with controls. Antiendomysium antibodies had a diagnostic sensitivity of 100% and the titers decreased significantly after 12 months of gluten exclusion. A significant positive correlation was found between antiendomysium antibody titers with both soluble interleukin-2 receptor and interleukin-6 values. CONCLUSIONS: The serum soluble interleukin-2 receptor and interleukin-6 levels may be used as a noninvasive measure of celiac disease activity and response to treatment.

The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance

Antecedentes: Durante a˜nos, el fluconazol se ha utilizado para tratar las infecciones por Candida. Sin embargo, el uso indiscriminado de este antimicótico ha favorecido la aparición de cepas resistentes. Se han descrito mutaciones en el gen ERG11 como uno de los principales mecanismos de resistencia en especies de Candida. Objetivos En el presente estudio se investigaron las mutaciones de sentido erróneo en genes ERG11 de aislamientos de Candida albicans, glabrata y tropicalis previamente examinados mediante pruebas de sensibilidad a fluconazol. Métodos: La detección de las mutaciones de este gen se realizó en 19 aislamientos clínicos de Candida (8 C. albicans, 5 C. glabrata y 6 C. tropicalis) sensibles y resistentes a fluconazol. El gen se amplificó mediante reacción en cadena de la polimerasa (PCR) con cebadores específicos para cada especie de Candida y se analizaron mediante secuenciación automatizada. Resultados: Se identificaron 14 mutaciones de sentido erróneo diferentes, 5 de las cuales no habían sido descritas previamente. Entre ellas, se identificó una nueva mutación L321F en un aislamiento de C. albicans resistente a fluconazol y que fue analizada mediante una estructura tridimensional teórica de ERG11p. Conclusión: La mutación L321F del gen ERG11 de C. albicans puede asociarse a resistencia a fluconazol (AU)

Background. For many years fluconazole has been commonly used to treat Candida infections. However, the indiscriminate use of this antimycotic therapy has favored the emergence of resistant isolates. Mutations in the ERG11 gene have been described as one of the primary mechanisms of resistance in Candida species. Aims. In this study we investigated missense mutations in ERG11 genes of Candida albicans, Candida glabrata and Candida tropicalis isolates previously evaluated by susceptibility testing to fluconazole. Methods. Screening for these mutations was performed on 19 Candida clinical isolates (eight C. albicans, five C. glabrata and six C. tropicalis) resistant and susceptible to fluconazole. The ERG11 gene was amplified by PCR with specific primers for each Candida species and analyzed by automated sequencing. Results. We identified 14 different missense mutations, five of which had not been described previously. Among them, a new mutation L321F was identified in a fluconazole resistant C. albicans isolate and it was analyzed by a theoretical three-dimensional structure of the ERG11p. Conclusion. The L321F mutation in C. albicans ERG11 gene may be associated with fluconazole resistance (AU)

Hospital malnutrition and inflammatory response in critically ill children and adolescents admitted to a tertiary intensive care unit

Critical illness has a major impact on the nutritional status of both children and adults. A retrospective study was conducted to evaluate the incidence of hospital malnutrition at a pediatric tertiary intensive care unit (PICU). Serum concentrations of IL-6 in subgroups of well-nourished and malnourished patients were also evaluated in an attempt to identify those with a potential nutritional risk. METHODS: A total of 1077 patients were enrolled. Nutritional status was evaluated by Z-score (weight for age). We compared mortality, sepsis incidence, and length of hospital stay for nourished and malnourished patients. We had a subgroup of 15 patients with severe malnutrition (MN) and another with 14 well-nourished patients (WN). Cytokine IL-6 determinations were performed by enzyme-linked immunosorbent assay. RESULTS: 53 percent of patients were classified with moderate or severe malnutrition. Similar amounts of C- reactive protein (CRP) were observed in WN and MN patients. Both groups were able to increase IL-6 concentrations in response to inflammatory systemic response and the levels followed a similar evolution during the study. However, the mean values of serum IL-6 were significantly different between WN and MN patients across time, throughout the study (p = 0.043). DISCUSSION: a considerable proportion of malnourished patients need specialized nutritional therapy during an intensive care unit (ICU) stay. Malnutrition in children remains largely unrecognized by healthcare workers on admission. CONCLUSIONS: The incidence of malnutrition was very high. Malnourished patients maintain the capacity to release inflammatory markers such as CRP and IL-6, which can be considered favorable for combating infections On the other hand, this capacity might also have a significant impact on nutritional status during hospitalization.

Efeitos da exposição à fumaça do cigarro sobre a produção láctea e o crescimento de filhotes de ratas / The effects of exposing rats to cigarette smoke on milk production and growth of offspring

OBJETIVOS: Analisar o efeito da exposição à fumaça do cigarro na gestação e lactação sobre a produção láctea de ratas, ganho ponderal e crescimento linear dos filhotes. MÉTODOS: Três grupos de ratas foram estudados na gestação e lactação: 15 ratas expostas à fumaça do cigarro mais fluxo de ar, 18 ratas manipuladas, isto é, expostas ao fluxo de ar comprimido e 18 ratas controle. Os filhotes foram medidos e pesados a cada 5 dias, do primeiro ao 15° dia. A produção láctea foi estimada pelos métodos de captação de leite em 1 hora e ganho ponderal dos filhotes. RESULTADOS: Os filhotes das ratas expostos à fumaça do cigarro apresentaram menor peso e comprimento ao nascer. Durante a lactação, os filhotes das ratas expostas à fumaça e das apenas manipuladas ganharam menos peso que o grupo controle. A produção láctea pelo método de captação de leite em 1 hora foi reduzida no grupo exposto à fumaça e, em menor proporção, nas ratas do grupo manipulado. Pelo método do ganho ponderal dos filhotes, a produção láctea reduziu-se igualmente nos grupos exposto à fumaça e manipulado, comparados ao grupo controle. CONCLUSÕES: A exposição à fumaça do cigarro comprometeu o peso e o comprimento ao nascer, mas, durante a lactação, também a manipulação comprometeu o ganho de peso dos filhotes. A manipulação e, mais acentuadamente, a exposição ao tabaco prejudicaram a produção de leite.

OBJECTIVES: To analyze the effects of exposure to cigarette smoke during gestation and lactation on the milk production of rats and on the weight gain and linear growth of their offspring. METHODS: Three groups of female rats were studied during gestation and lactation: 15 rats were exposed to cigarette smoke and air flow, 18 rats were handled, i.e., exposed to compressed air flow, and 18 rats were used as controls. Newborn rats were measured and weighed every 5 days, from the first to the 15th day. Milk production was estimated by 1-hour milk extraction and weight gained by litters. RESULTS: The offspring of rats exposed to cigarette smoke weighed less and were shorter at birth. During lactation, the offspring of rats exposed to smoke and also of rats that had merely been handled gained less weight than the control group. Milk production gauged by the 1-hour extraction method was reduced in the group exposed to smoke and, to a lesser extent, also in the group that had been handled. Milk production estimated according to the pups' weight gain was reduced equally in the groups exposed to smoke and merely handled, when compared to the control group. CONCLUSIONS: Exposure to cigarette smoke compromised the birth weight and birth length, but during lactation, handling also compromised weight gain of offspring. Handling and, to a greater extent, exposure to tobacco, were prejudicial to milk production.

Interleucina 6 e proteína c reativa no diagnóstico de sepse tardia no recém-nascido / Interleukins 6 and c - reactive protein for the diagnosis of late onset sepsis in the newborn infant

OBJETIVO: Verificar a acurácia da interleucina 6 (IL-6) e da proteína C reativa (PCR) para o diagnóstico de sepse tardia no recém-nascido (RN). MÉTODOS: Trata-se de estudo de coorte prospectivo com 43 RNs internados com suspeita de sepse tardia na UTIN. Foram dosados no dia da suspeita diagnóstica (dia 0) e nos dias 1, 3 e 7 de evolução os níveis séricos da IL-6 e da PCR e calculado o melhor valor de coorte para o diagnóstico de sepse. Também foram calculados os índices de sensibilidade (S), especificidade (E), valor preditivo positivo e negativo (VPP, VPN) para cada um dos testes, assim como para a combinação entre eles. RESULTADOS: Os níveis séricos da IL-6 e da PCR estiveram acima do ponto de coorte nos RN com sepse e com sepse presumível com diferenças significantes entre ambos os grupos, nos quais a única diferença foi hemocultura positiva no primeiro. Foi possível afastar esse diagnóstico em seis RNs. Para o diagnóstico de sepse, a IL-6 obteve os melhores índices no dia da suspeita diagnóstica, dia 0 (S: 88,9 por cento, E: 80 por cento, VPP: 76,2 por cento, VPN: 90,9 por cento), seguida da proteína C reativa (S: 94 por cento, E: 78,3 por cento, VPP: 77,3 por cento, VPN: 94,7 por cento) 24 horas após. A combinação dos dois (IL 6/PCR) mostrou-se mais adequada para o diagnóstico precoce no dia 0 e até 24 horas de evolução com S e VPN de 100 por cento. CONCLUSÃO: A combinação de IL6/PCR apresentou acurácia para o diagnóstico de sepse. A evolução destes testes ao longo dos dias refletiu a evolução clínica dos RN.

Monitoring the treatment of sepsis with vancomycin in term newborn infants

A prospective study was conducted to determine if standardized vancomycin doses could produce adequate serum concentrations in 25 term newborn infants with sepsis. Purpose: The therapeutic response of neonatal sepsis by Staphylococcus sp. treated with vancomycin was evaluated through serum concentrations of vancomycin, serum bactericidal titers (SBT), and minimum inhibitory concentration (MIC). METHOD: Vancomycin serum concentrations were determined by the fluorescence polarization immunoassay technique , SBT by the macro-broth dilution method, and MIC by diffusion test in agar . RESULTS: Thirteen newborn infants (59.1 percent) had adequate peak vancomycin serum concentrations (20--40 mg/mL) and one had peak concentration with potential ototoxicity risk (>40 æg/mL). Only 48 percent had adequate trough concentrations (5--10 mg/mL), and seven (28 percent) had a potential nephrotoxicity risk (>10 æg/mL). There was no significant agreement regarding normality for peak and trough vancomycin method (McNemar test : p = 0.7905). Peak serum vancomycin concentrations were compared with the clinical evaluation (good or bad clinical evolution) of the infants, with no significant difference found (U=51.5; p=0.1947). There was also no significant difference between the patients' trough concentrations and good or bad clinical evolution (U = 77.0; p=0.1710). All Staphylococcus isolates were sensitive to vancomycin according to the MIC. Half of the patients with adequate trough SBT (1/8), also had adequate trough vancomycin concentrations and satisfactory clinical evolution. CONCLUSIONS: Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. SBT interpretation should be made in conjunction with the patient's clinical presentation and vancomycin serum concentrations. Those laboratory and clinical data favor elucidation of the probable cause of patient's bad evolution, which would facilitate drug adjustment and reduce the risk of toxicity or failing to achieve therapeutic doses

Vancomycin monitoring in term newborns: comparison of peak and trough serum concentrations determined by high performance liquid chromatography and fluorescence polarization immunoassay

INTRODUCTION: Peak and trough serum concentrations of vancomycin were determined in term newborn infants with confirmed or suspected Staphylococcus sp sepsis by high performance liquid chromatography and flourescence polarization immunoassay. OBJECTIVE: To statistically compare the results of the high performance liquid chromatography and flourescence polarization immunoassay techniques for measuring serum vancomycin concentrations. METHODS: Eighteen peak and 20 trough serum samples were assayed for vancomycin concentrations using high performance liquid chromatography and flourescence polarization immunoassay from October 1995 to October 1997. RESULTS: The linear correlation coefficients for high performance liquid chromatography and flourescence polarization immunoassay were 0.27 (peak, P = 0.110) and 0.26 (trough, P = 0.1045) respectively, which were not statistically significant. CONCLUSION: There was wide variation in serum vancomycin concentrations determined by high performance liquid chromatography as compared with those determined by flourescence polarization immunoassay. There was no recognizable pattern in the variability; in an apparently random fashion, the high performance liquid chromatography measurement was sometimes substantially higher than the flourescence polarization immunoassay measurement, and at other times it was substantially lower