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OBJECTIVE: To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infantsâ<33 wk gestation. DESIGN/METHODS: Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. RESULTS: Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants wereâ<28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, pâ<â0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rhâ>â0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, pâ=â0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, pâ=â0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; pâ=â0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. CONCLUSIONS: Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infantsâ<33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.
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Nutrición Enteral/métodos , Transfusión de Eritrocitos , Recien Nacido Prematuro/fisiología , Absorción Intestinal/fisiología , Mucosa Intestinal/fisiología , Lactosa/metabolismo , Ramnosa/metabolismo , Nutrición Enteral/efectos adversos , Femenino , Edad Gestacional , Hematócrito , Humanos , Fórmulas Infantiles , Fenómenos Fisiológicos Nutricionales del Lactante/fisiología , Recién Nacido , Masculino , Leche Humana , Estudios RetrospectivosRESUMEN
Congenital central hypoventilation syndrome (CCHS) is an uncommon cause of apnea in the newborn characterized by the occurrence of apnea predominantly during sleep. Haddad syndrome is CCHS with Hirschsprung's disease. We report a newborn with Haddad syndrome that had a family history of spinal muscular atrophy and discuss aspects of CCHS and important considerations in the evaluation of apnea in the term newborn.
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Enfermedad de Hirschsprung/diagnóstico , Proteínas de Homeodominio/genética , Hipoventilación/congénito , Mutación/genética , Apnea Central del Sueño/etiología , Factores de Transcripción/genética , Dióxido de Carbono/sangre , Asesoramiento Genético , Enfermedad de Hirschsprung/genética , Humanos , Hipoventilación/diagnóstico , Hipoventilación/genética , Recién Nacido , Masculino , Monitoreo Fisiológico , Pronóstico , Apnea Central del Sueño/diagnóstico , Apnea Central del Sueño/genética , SíndromeRESUMEN
The pain and risk of infection associated with invasive blood sampling for blood gas measurements necessitate the search for reliable noninvasive techniques. In this work we developed a novel rate-based noninvasive method for a safe and fast assessment of respiratory status. A small sampler was built to collect the gases diffusing out of the skin. It was connected to a CO2 sensor through gas-impermeable tubing. During a measurement, the CO2 initially present in the sampler was first removed by purging it with nitrogen. The gases in the system were then recirculated between the sampler and the CO2 sensor, and the CO2 diffusion rate into the sampler was measured. Because the measurement is based on the initial transcutaneous diffusion rate, reaching mass transfer equilibrium and heating the skin is no longer required, thus, making it much faster and safer than traditional method. A series of designed experiments were performed to analyze the effect of the measurement parameters such as sampler size, measurement location, subject positions, and movement. After the factor analysis tests, the prototype was sent to a level IV NICU for clinical trial. The results show that the measured initial rate of increase in CO2 partial pressure is linearly correlated with the corresponding arterial blood gas measurements. The new approach can be used as a trending tool, making frequent blood sampling unnecessary for respiratory status monitoring.
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Análisis de los Gases de la Sangre/métodos , Dióxido de Carbono/sangre , Respiración , Piel , Adulto , Análisis de los Gases de la Sangre/efectos adversos , Análisis de los Gases de la Sangre/instrumentación , Dióxido de Carbono/metabolismo , Difusión , Análisis Factorial , Femenino , Humanos , Lactante , Unidades de Cuidado Intensivo Neonatal , Ventilación Pulmonar , Seguridad , Factores de TiempoRESUMEN
OBJECTIVES: To evaluate the relationship between fetal Doppler parameters, biophysical profile score (BPP) and neurodevelopmental delay at 2 years of corrected age in infants who had been growth-restricted in utero. METHODS: This was a prospective observational study including 113 pregnancies complicated by intrauterine growth restriction (IUGR) (abdominal circumference<5th percentile and elevated umbilical artery (UA) pulsatility index). The relationships of UA, middle cerebral artery and ductus venosus (DV) Doppler features, BPP, birth acidemia (artery pH<7.0+/or base deficit>12), gestational age at delivery, birth weight and neonatal morbidity (i.e. bronchopulmonary dysplasia, >Grade 2 intraventricular hemorrhage, or necrotizing enterocolitis) with a 2-year neurodevelopmental delay were evaluated. Best Beginnings Developmental Screen, Bayley Scale of Infant Development II (BSID) and Clinical Adaptive/Clinical Linguistic Auditory Milestone Stage were used. BSID<70, cerebral palsy, abnormal tone, hearing loss and/or blindness defined neurodevelopmental delay. RESULTS: Seventy-two of the 113 pregnancies completed assessment; there were 10 stillbirths, 19 neonatal deaths, three infant deaths and nine pregnancies with no follow-up. Twenty fetuses (27.8%) had UA reversed end-diastolic velocity (REDV), 34 (47.2%) abnormal DV Doppler features and 31 (43.1%) an abnormal BPP. Median gestational age at delivery and birth weight were 30.4 weeks and 933 g, respectively. Twelve infants had acidemia and 28 neonatal morbidity. There were 38 (52.8%) infants with neurodevelopmental delay, including 37 (51.4%) with abnormal tone, 20 (27.8%) with speech delay, 23 (31.9%) with an abnormal neurological examination, eight (11.1%) with a hearing deficit and six (8.3%) with cerebral palsy. Gestational age at delivery was associated with cerebral palsy (r2=0.52, P<0.0001; 92% sensitivity and 83% specificity for delivery at <27 weeks). UA-REDV was associated with global delay (r2=0.31, P=0.006) and birth weight with neurodevelopmental delay (r2=0.54, P<0.0001; 82% sensitivity and 64% specificity for BW<922 g). CONCLUSIONS: Although UA-REDV is an independent contributor to poor neurodevelopment in IUGR no such effect could be demonstrated for abnormal venous Doppler findings or BPP. Gestational age and birth weight remain the predominant factors for poor neurodevelopment in growth-restricted infants.
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Discapacidades del Desarrollo/etiología , Retardo del Crecimiento Fetal/diagnóstico por imagen , Insuficiencia Placentaria/diagnóstico por imagen , Arterias Umbilicales/diagnóstico por imagen , Adolescente , Adulto , Ceguera/embriología , Velocidad del Flujo Sanguíneo/fisiología , Parálisis Cerebral/embriología , Preescolar , Femenino , Monitoreo Fetal , Pérdida Auditiva/embriología , Humanos , Lactante , Recién Nacido , Masculino , Arteria Cerebral Media/diagnóstico por imagen , Embarazo , Estudios Prospectivos , Ultrasonografía Prenatal , Adulto JovenRESUMEN
OBJECTIVE: As Ureaplasmas may be pathogens in preterm infants, this study was conducted to determine the incidence of invasive disease with Ureaplasma parvum and Ureaplasma urealyticum and the relationship with adverse outcomes in a prospective cohort of very low birth weight (VLBW) infants. STUDY DESIGN: DNA was extracted from the cord or venous blood and cerebrospinal fluid (CSF) samples obtained from 313 VLBW infants. PCR was performed using primers for the mba gene to detect all 14 serovars and then repeated for all positive samples using species-specific primers. RESULT: Ureaplasma species were detected in serum and/or CSF samples from 74 of 313 (23.6%) infants. U. parvum was the predominant species (70%). Presence of Ureaplasma was significantly associated with elevated interleukin-1beta in cord blood (odds ratio (OR) 2.6, 1.05 to 6.45, P=0.039). Ureaplasma serum-positive infants had a 2.3-fold increased risk of intraventicular hemorrhage > or =grade 3 (OR 2.50; 1.06 to 5.89, P=0.036). CONCLUSION: Invasive Ureaplasma occurs commonly in VLBW infants and may increase the risk for severe intraventricular hemorrhage.
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Bacteriemia/complicaciones , Hemorragia Cerebral/microbiología , Líquido Cefalorraquídeo/microbiología , Enfermedades del Prematuro , Infecciones por Ureaplasma/complicaciones , Bacteriemia/microbiología , Displasia Broncopulmonar/microbiología , Hemorragia Cerebral/complicaciones , Femenino , Sangre Fetal/microbiología , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/microbiología , Recién Nacido de muy Bajo Peso , Placenta/microbiología , Placenta/patología , Estudios Prospectivos , Ureaplasma/aislamiento & purificaciónRESUMEN
OBJECTIVE: To evaluate relationships between neonatal intraventricular hemorrhage and altered brain blood flow in preterm growth-restricted fetuses. METHODS: One hundred and thirteen growth-restricted fetuses (birth weight < 10th centile and umbilical artery pulsatility index > two standard deviations above gestational age mean) which delivered prematurely (< 34.0 weeks) were studied. Three expressions of altered brain blood flow were defined: 'brain sparing'= middle cerebral artery pulsatility index > two standard deviations below the gestational age mean, 'centralization' = ratio of middle cerebral artery/umbilical artery pulsatility indices (cerebroplacental ratio) > two standard deviations below the gestational age mean, and 'redistribution' = absent or reversed umbilical artery end-diastolic velocity. Intraventricular hemorrhage was graded after Papile (I-IV) by cranial ultrasound performed within 7 days of delivery. RESULTS: Sixty-seven (59.3%) fetuses had brain sparing, 84 (74.3%) had centralization and 51 (45.1%) had redistribution. Fifteen (13.3%) neonates had intraventricular hemorrhage and were more likely to have a biophysical profile < 6, earlier delivery for fetal indications, lower cord artery pH, HCO3, hemoglobin, and platelets, a 10-min Apgar score < 7 and high perinatal mortality (5/15; 33.3%). No associations between intraventricular hemorrhage and brain sparing or centralization were identified. However, neonates with intraventricular hemorrhage had significantly higher umbilical artery pulsatility index deviations from the gestational age mean and a relative risk of 4.9-fold for intraventricular hemorrhage with redistribution (95% confidence interval, 1.5-16.3; P < 0.005). Multiple logistic regression revealed significant associations between intraventricular hemorrhage and a low 10-min Apgar score (r = 0.30, P < 0.005) and low hemoglobin (r = 0.28), gestational age at delivery (r = 0.25) and birth-weight centiles (r = 0.23) (P < 0.05). No Doppler parameter was identified as an independent contributor to intraventricular hemorrhage. CONCLUSION: While loss of umbilical artery end-diastolic velocity early in gestation significantly increases the risk for neonatal intraventricular hemorrhage, prematurity and difficult transition to extrauterine life remain the most important determinants of intraventricular hemorrhage.
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Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/fisiopatología , Retardo del Crecimiento Fetal/fisiopatología , Flujometría por Láser-Doppler , Ultrasonografía Prenatal , Puntaje de Apgar , Velocidad del Flujo Sanguíneo , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/embriología , Arterias Cerebrales/fisiología , Circulación Cerebrovascular , Femenino , Retardo del Crecimiento Fetal/diagnóstico por imagen , Humanos , Recién Nacido , Modelos Logísticos , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Arterias Umbilicales/diagnóstico por imagen , Arterias Umbilicales/fisiologíaRESUMEN
We previously observed that Ureaplasma urealyticum respiratory tract colonization in infants with a birth weight of < or =1,250 g was associated with increases in the tracheal aspirate proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-8 (IL-8) relative to the counterregulatory cytokine IL-6 during the first week of life (A. M. Patterson, V. Taciak, J. Lovchik, R. E. Fox, A. B. Campbell, and R. M. Viscardi, Pediatr. Infect. Dis. J. 17:321-328, 1998). We hypothesized that U. urealyticum alters the host immune response in the presence of a coinflammatory stimulus (e.g., bacterial infection or hyperoxia) by shifting the balance of cytokine expression towards the proinflammatory cytokines. To test this hypothesis, we compared the release of TNF-alpha, IL-8, IL-6, and IL-10 in vitro by unstimulated and U. urealyticum (with or without lipopolysaccharide [LPS])-stimulated human monocytes from adult peripheral blood and from term and preterm cord blood. U. urealyticum alone and in combination with LPS induced concentration- and development-dependent changes in cytokine release. In vitro inoculation with low-inoculum U. urealyticum (10(3) color-changing units [CCU]) (i) partially blocked the LPS-stimulated IL-6 release by all cells and reduced LPS-stimulated IL-10 release by preterm cells, (ii) stimulated TNF-alpha and IL-8 release by preterm cells, and (iii) augmented LPS-stimulated TNF-alpha release in all cells. In preterm cells, high-inoculum U. urealyticum (10(6) CCU) (i) stimulated TNF-alpha and IL-8, but not IL-6 or IL-10, release and (ii) augmented LPS-stimulated TNF-alpha and IL-8 release. High-inoculum U. urealyticum (i) stimulated release of all four cytokines in term cells and IL-8 release in adult cells and (ii) augmented LPS-induced TNF-alpha, IL-10, and IL-8 release in term cells but did not significantly affect LPS-induced cytokine release in adult cells. We speculate that U. urealyticum enhances the proinflammatory response to a second infection by blocking expression of counterregulatory cytokines (IL-6 and IL-10), predisposing the preterm infant to prolonged and dysregulated inflammation, lung injury, and impaired clearance of secondary infections.
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Citocinas/metabolismo , Sangre Fetal/citología , Lipopolisacáridos/farmacología , Monocitos/inmunología , Ureaplasma urealyticum/inmunología , Adulto , Humanos , Recién Nacido , Recien Nacido Prematuro , Monocitos/efectos de los fármacos , Monocitos/microbiología , Infecciones por Ureaplasma/microbiología , Ureaplasma urealyticum/metabolismoRESUMEN
OBJECTIVE: To determine whether placental lesions are risk factors for neurologic morbidities in intrauterine growth restricted (IUGR) infants, we compared the incidence of cranial ultrasound (CUS) abnormalities and the number and type of placental lesions in IUGR cases and gestational age-matched appropriate for gestational age (AGA) controls. STUDY DESIGN: Retrospective case-control study of 94 singleton IUGR and 145 AGA infants. Medical records, CUS reports, and placental histology were reviewed. Analyses included chi2, t-test, analysis of variance and logistic regressions to identify those variables significantly associated with IUGR and those associated with CUS abnormalities. RESULTS: The incidence of CUS abnormalities was 1.7-fold higher in IUGR cases (50%) than controls (29.7%) (p<0.05). A total placental lesion score of > or =3 was associated with an increased risk for IUGR (OR 14.18, 3.41-58.99; p<0.001) and increased risk for CUS abnormality (OR 12.571, 3.33-47.416; p<0.05). In a logistic regression model only > or =2 placental lesions, IUGR and gestational age <30 weeks were significant independent predictors of CUS abnormalities. CONCLUSIONS: The severity of placental abnormalities expressed as the cumulative number of placental lesions is a significant risk factor for IUGR and perinatal brain injury. These results suggest that abnormal uteroplacental or fetoplacental blood flow may adversely affect intrauterine growth and increase the risk for brain injury.
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Trastornos Cerebrovasculares/etiología , Retardo del Crecimiento Fetal/etiología , Enfermedades Placentarias/complicaciones , Adulto , Estudios de Casos y Controles , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/epidemiología , Infarto Cerebral/etiología , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/epidemiología , Femenino , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/patología , Edad Gestacional , Humanos , Recién Nacido , Hemorragias Intracraneales/diagnóstico por imagen , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Leucomalacia Periventricular/diagnóstico por imagen , Leucomalacia Periventricular/epidemiología , Leucomalacia Periventricular/etiología , Enfermedades Placentarias/epidemiología , Enfermedades Placentarias/patología , Embarazo , Estudios Retrospectivos , Factores de Riesgo , UltrasonografíaRESUMEN
Fetal lung fibroblasts provide lipid substrate for type II cell surfactant phospholipid synthesis. This process is developmental and glucocorticoid dependent. Previous studies in our laboratory demonstrating sex differences in several aspects of lung maturation suggest that these differences may be due to effects of fetal androgens. Based on these studies, we hypothesized that fetal lung fibroblast triglyceride metabolism is determined by opposing effects of fetal androgens and glucocorticoids. To model the effects of androgens on fetal lung fibroblast triglyceride metabolism, pregnant rats were treated with dihydrotestosterone (DHT) 1 mg/kg/day from the days 15 to 20 of gestation, and changes in triglyceride content of freshly isolated fetal rat lung fibroblasts (FRLF) and rates of uptake and prostaglandin E2 (PGE2)-mediated release by cultured FRLF in response to glucocorticoids in the presence or absence of DHT in vitro were measured. During lung development, the triglyceride content and rate of uptake of female-derived FRLF increased 3.5- and 4.8-fold, respectively, between days 18 and 20 of gestation. From days 19 to 22, male FRLF trigyclyceride content and rate of uptake were lower than the content and uptake by female FRLF. Maternal DHT treatment inhibited the normal developmental increase in fibroblast triglyceride content and rate of uptake between days 19 and 22 by both male and female FRLF. In the absence of maternal DHT, in vitro dexamethasone stimulated triglyceride uptake 3-fold by day 21 in FRLF. This effect was blocked by maternal pretreatment with DHT. Maternal DHT exposure prevented stimulation of triglyceride release by PGE2. Although in vitro dexamethasone stimulated triglyceride release by maternal DHT-exposed fibroblasts, it did not enhance the response to PGE2. These data suggest that in utero exposure to androgens (1) delay the developmental increase in triglyceride content and (2) oppose the effects of glucocorticoid on cultured FRLF triglyceride uptake and PGE2-mediated release.
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Dihidrotestosterona/farmacología , Feto/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Pulmón/embriología , Triglicéridos/metabolismo , Animales , Dexametasona/farmacología , Dinoprostona/farmacología , Combinación de Medicamentos , Femenino , Glucocorticoides/farmacología , Pulmón/citología , Embarazo , Ratas , Ratas Sprague-Dawley , Triglicéridos/antagonistas & inhibidoresRESUMEN
We previously reported that expression of tumor necrosis factor-alpha (TNFalpha) was attenuated in macrophages exposed to febrile range temperatures. In this study, we analyzed the influence of temperature on TNFalpha transcription in the Raw 264.7 macrophage cell line during incubation at 37 and 39.5 degrees C. The initial activation of TNFalpha transcription in response to endotoxin (LPS) was comparable in the 37 and 39.5 degrees C cell cultures, peaking within 10 min of LPS stimulation. However, the duration of transcriptional activation was markedly reduced in the 39.5 degrees C cells (30-60 min) compared with the 37 degrees C cells (2-4 h). Deletion mapping of the TNFalpha gene revealed that the proximal 85-nucleotide promoter sequence and the 5'-untranslated region were sufficient for temperature sensitivity. This sequence contains six heat shock response element (HRE) half-sites but no complete HREs. Electrophoretic mobility shift and immunoblot assays demonstrated that nuclear transclocation of heat shock factor (HSF) and its activation to a DNA-binding form occurred in the 39.5 degrees C cells in the absence of heat shock protein-70 gene activation. The proximal TNFalpha promoter/5'-untranslated region sequence competed for HSF binding to a classic HRE. Overexpression of HSF-1 reduced activity of the TNFalpha promoter. These data suggest that partial activation of HSF-1 during exposure to febrile, sub-heat shock temperatures may block TNFalpha transcription by binding to its proximal promoter or 5'-untranslated region.
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Proteínas de Unión al ADN/fisiología , Fiebre/genética , Regulación de la Expresión Génica/fisiología , Macrófagos/metabolismo , Transcripción Genética , Factor de Necrosis Tumoral alfa/genética , Animales , Secuencia de Bases , Línea Celular , Cartilla de ADN , Factores de Transcripción del Choque Térmico , Ratones , Regiones Promotoras Genéticas , Unión Proteica , Factores de Transcripción , Transcripción Genética/fisiología , Activación TranscripcionalRESUMEN
Fever, a nonspecific acute-phase response, has been associated with improved survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reported that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-6, three cytokines critical to mounting an initial defense against microbial pathogens, but survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in the warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was to determine if increasing murine core temperature altered cytokine expression and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5 degrees C rather than 23 degrees C increased core temperature from 36.5 to 37.5 degrees C to 39.2 to 39.7 degrees C, suppressed plasma TNF-alpha expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load in mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proliferation and probably reflected enhanced host defense. These data suggest that the increase in core temperature that occurs during bacterial infections is essential for optimal antimicrobial host defense.
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Fiebre/etiología , Infecciones por Klebsiella/fisiopatología , Klebsiella pneumoniae , Peritonitis/fisiopatología , Animales , Temperatura Corporal , Interferón gamma/sangre , Interleucina-6/sangre , Lipopolisacáridos/toxicidad , Masculino , Ratones , Factor de Necrosis Tumoral alfa/análisisRESUMEN
We have shown previously that febrile range temperatures modify cytokine production by adult macrophages. In this study, we compared the effects of moderate hyperthermia and hypothermia on the kinetics of lipopolysaccharide (LPS)-induced cytokine expression in monocytes and macrophages of newborns and adults. During culture at 40 degrees C, the initial rates of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) secretion were preserved, but the duration of secretion was shorter than the duration at 37 degrees C. TNF-alpha and IL1-beta concentrations in 24-h 40 degrees C culture supernatants were reduced 18%-50%. IL-6 concentration in 24-h 40 degrees C cultures was reduced 26%-29% in all cells except adult macrophages. At 32 degrees C, changes in early (2 h) and sustained (24 h) cytokine expression were reversed compared with those caused by hyperthermia. Culturing adult macrophages at 32 degrees C blunted early secretion of TNF-alpha and IL-6 by 69% and 65%, respectively, and increased TNF-alpha concentration at 24 h by 48% compared with levels at 37 degrees C. In adult monocytes cultured at 32 degrees C, early IL-6 and IL-1 beta secretion was decreased 64% and 51%, respectively. We speculate that the burst/suppression cytokine profile at febrile temperatures might enhance early activation of host defenses and prevent prolonged exposure to potentially cytotoxic cytokines. Hypothermia, on the other hand, may worsen outcome in infections by delaying and prolonging cytokine production.
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Citocinas/metabolismo , Fagocitos/metabolismo , Adulto , Factores de Edad , Células Cultivadas , Citocinas/biosíntesis , Humanos , Hipertermia Inducida , Hipotermia Inducida , Recién Nacido , TemperaturaRESUMEN
The phospholipid transfer proteins (PLTPs) are cytosolic proteins that have been characterized by their ability to facilitate the transfer of phospholipids between membranes in vitro. The goals of this study were to determine whether PITP alpha concentration and phospholipid transfer activities are enriched in type II cells compared with whole lung and to determine the developmental changes in PITP alpha concentration and phospholipid transfer activities during late gestation and newborn period. The concentration of PITP alpha in type II cell cytosol measured by enzyme-linked immunosorbent assay (ELISA) increased during late fetal gestation to 2.2-fold adult levels and declined 41% during the first postnatal day. However, compared to whole adult lung cytosol, type II cell cytosol was not significantly enriched with PITP alpha. Phospholipid transfer activities were determined by a vesicle-rat lung membrane transfer assay. In adult lung, transfer activities for all the phospholipids were enriched in adult type II cell cytosol compared to whole lung cytosol (phosphatidylglycerol [PG], 12.5-fold; phosphatidylinositol [PI], 9.2-fold; phosphatidylcholine [PC], 6.5-fold; and phosphatidylethanolamine [PE], 6.6-fold; P < .05 in each case). The rate of phospholipid transfer in type II cell cytosol increased during late fetal gestation to levels 4.9 (PG), 3.7 (PI), and 2.8 (PC) times greater than adult levels. In cytosol from cells from different stages, the order of transfer rate was PG > PI > PC > PE. PITP alpha immunodepletion of adult type II cytosol did not significantly affect phospholipid transfer activities, suggesting that other PLTPs are responsible for the majority of the observed transfer activities in these cells. Developmental increases in PITP alpha concentration and other PLTPs parallel developmental changes in type II cell surfactant phospholipid metabolism, suggesting a possible role of these transfer proteins in the unique function of the type II cell.
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Proteínas Portadoras/metabolismo , Proteínas de la Membrana , Fosfatidilinositoles/metabolismo , Fosfolípidos/metabolismo , Alveolos Pulmonares/metabolismo , Animales , Animales Recién Nacidos , Citosol/metabolismo , Femenino , Feto/citología , Feto/metabolismo , Masculino , Proteínas de Transferencia de Fosfolípidos , Embarazo , Alveolos Pulmonares/citología , Alveolos Pulmonares/crecimiento & desarrollo , Ratas , Ratas Sprague-Dawley , Fracciones Subcelulares/metabolismoRESUMEN
OBJECTIVE: To determine whether Ureaplasma urealyticum respiratory tract colonization in very low birth weight infants during the first week of life is associated with changes in tracheal aspirate concentrations of the cytokines interleukin 1-beta (IL-1-beta), tumor necrosis factor alpha (TNF-alpha) and IL-6. METHODS: Infants with birth weights < or =1250 g were prospectively enrolled. Samples were obtained from the endotracheal tube or nasopharynx on Day 1 and again between Days 7 and 10 for U. urealyticum culture. The concentrations of IL-1-beta, TNF-alpha and IL-6 were measured in tracheal aspirate samples by enzyme-linked immunosorbent assay. RESULTS: There were 18 positive cultures for U. urealyticum from 15 of 96 infants (15.6%). IL-1-beta in tracheal aspirates expressed as concentration per volume or as a ratio of IL-1-beta to IL-6 were 7- and 14.9-fold higher, respectively, in Ureaplasma-positive infants than in Ureaplasma-negative infants (P < 0.05). The TNF-alpha/IL-6 ratio was 18.9 and 15.5 times higher in the Ureaplasma-positive aspirates than in the Ure aplasma-negative aspirates on Day 1 and Days 7 to 10 (P < 0.05). Concentrations of IL-1-beta and TNF-alpha were significantly correlated on Day 1 and Days 7 to 10. Although there was no clinical association demonstrated between U. urealyticum colonization and the development of bronchopulmonary dysplasia (BPD) in this study, infants who developed BPD had significantly higher IL-1-beta concentrations and ratios of IL-1-beta to IL-6 in Day 1 aspirates than infants who did not develop BPD. Conclusions. Isolation of U. urealyticum from the respiratory tract is associated with increased IL-1-beta concentrations and IL-1-beta-IL-6 ratios on Day 1 and increased TNF-alpha-IL-6 ratios on Days 1 and 7 to 10 in tracheal aspirates of colonized infants. Infants who developed BPD had higher IL-1-beta concentrations and IL-1-beta-IL-6 ratios, suggesting that these may be early markers of lung inflammation.
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Citocinas/análisis , Recien Nacido Prematuro , Nasofaringe/microbiología , Tráquea/inmunología , Tráquea/microbiología , Ureaplasma urealyticum/aislamiento & purificación , Displasia Broncopulmonar/microbiología , Displasia Broncopulmonar/terapia , Citocinas/inmunología , Humanos , Recién Nacido , Interleucina-1/análisis , Interleucina-6/análisis , Intubación Intratraqueal , Estudios Prospectivos , Factor de Necrosis Tumoral alfa/análisis , Ureaplasma urealyticum/crecimiento & desarrolloRESUMEN
PURPOSE: To learn how parents perceived their experiences during a visit to an academic center's NICU follow-up clinic and what they would change about the clinic if given the opportunity. DESIGN: A qualitative study utilizing artifact collection, participant observation, and semistructured interviews. SAMPLE: Seven families that went to the clinic. MAIN OUTCOME VARIABLE: What parents did and did not like about the clinic and what they would change about the clinic. RESULTS: Parent concerns included lack of information about the clinic prior to the first appointment, length of wait prior to seeing the physician, preference for more appropriate toys for use during the wait, desire for additional explanations during the exam process, uncertainty about the effects of prematurity on their child's development, and need for more developmental and parenting information.
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Cuidados Posteriores , Cuidado del Lactante/normas , Padres/psicología , Percepción , Citas y Horarios , Desarrollo Infantil , Comportamiento del Consumidor , Femenino , Humanos , Lactante , Cuidado Intensivo Neonatal , Masculino , Investigación en Evaluación de Enfermería , Servicio Ambulatorio en HospitalRESUMEN
An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD.
Asunto(s)
Displasia Broncopulmonar/prevención & control , Cromolin Sódico/uso terapéutico , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Displasia Broncopulmonar/metabolismo , Recuento de Células , Método Doble Ciego , Ensayo de Inmunoadsorción Enzimática , Humanos , Recién Nacido , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Macrófagos/citología , Neutrófilos/citología , Estudios Prospectivos , Factores de Riesgo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Coagulation necrosis, inflammation, and hemorrhage are pathologic hallmarks of necrotizing enterocolitis (NEC). Because cytokines are peptides that mediate inflammatory cell recruitment and amplify the immune response, several of the inflammatory cytokines have been implicated in NEC. We hypothesized that mRNA levels for the interrelated cytokines interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and the neutrophil chemotactic factor IL-8 would be increased in NEC and would be associated with the presence of inflammation. In this study, we determined the relative levels and localization of mRNA for these cytokines in surgical pathology archival intestinal tissue from 29 premature infants with acute NEC and 15 control infants with congenital intestinal malformations using a novel quantitative in situ hybridization technique. Compared with controls, there were higher IL-1 beta mRNA levels in full-thickness sections and higher TNF-alpha mRNA levels in full-thickness and mucosa sections of acute NEC samples, suggesting a potential role for these cytokines in the pathogenesis of local inflammation in NEC. IL-6 and IL-8 mRNA levels were similar in samples of control and acute NEC cases. Analysis of covariance including all subjects showed that the presence of acute inflammation was associated with increased IL-1 beta mRNA levels in mucosa (P = .035) and increased IL-8 in full-thickness sections (P = .005) and mucosa (P = .01). In four of five NEC cases in which intestinal specimens were available from reanastomosis surgery, cytokine mRNA levels decreased to low or undetectable levels. These data suggest that the inflammatory cytokines are involved in neutrophil recruitment and augmentation of the inflammatory response in neonatal intestine.
Asunto(s)
Citocinas/genética , Enterocolitis Seudomembranosa/metabolismo , Enterocolitis Seudomembranosa/patología , Mucosa Intestinal/metabolismo , Intestinos/patología , ARN Mensajero/análisis , Enterocolitis Seudomembranosa/cirugía , Femenino , Humanos , Recién Nacido , Interleucina-1/genética , Interleucina-6/genética , Interleucina-8/genética , Intestinos/cirugía , Masculino , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
The arterious venous oxygen difference (AVDO2) due to the close relationship with cerebral metabolic rate of oxygen and cerebral blood flow shows metabolic alterations that occur in some pathological situations in the brain including subarachnoid haemorrhage. The AVDO2 was calculated by the Fick equation and the results evaluated by the Glasgow outcome scale. Measurements of arteriojugular oxygen difference were carried out in 30 patients with subarachnoid haemorrhage due to rupture of intracranial aneurysms, as an attempt to monitor the relationship between changes in AVDO2, clinical picture, and evolution of the patients. The subarachnoid haemorrhage was diagnosed by CT scan in 17 patients and by lumbar punction in 13 and the diagnosis of arterial vasospasm was carried out by clinical evaluation and confirmed by four vessels angiogram in only eight patients. Eighteen patients were admitted with Hunt & Hess (H&H) I/II, seven with H&H III and five with H&H IV/V. Nineteen patients had AVDO2 normal and this group had three deaths; five patients had AVDO2 continuously low with three deaths; and six patients had AVDO2 continuously high with two deaths. The patients with normal AVDO2 had better prognosis and clinical evolution than the patients with abnormal values of AVDO2. In conclusion, AVDO2 measurements could not be correlated with the diagnosis of vasospasm, but was useful in the early identification of metabolic changes that occur after subarachnoid haemorrhage and could be used as an supplementary monitoring in the clinical evaluation of patients with this pathology.
Asunto(s)
Aneurisma Intracraneal/complicaciones , Oxígeno/metabolismo , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/metabolismo , Adulto , Femenino , Escala de Coma de Glasgow , Humanos , Ataque Isquémico Transitorio , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Pronóstico , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/mortalidadRESUMEN
Activity of cholinephosphate cytidylyltransferase, the rate-limiting enzyme in phosphatidylcholine synthesis, increases rapidly in the lung after birth predominantly due to an increase in membrane-associated activity. Although there is strong evidence that enzyme translocation is a major regulatory mechanism in other cells, this mechanism has not been conclusively demonstrated in intact alveolar type II cells. In this study, we show that oleic acid stimulates rapid translocation of cytidylyltransferase activity and protein from cytosol to microsomes in both primary cultured fetal and adult type II cells and MLE12 cells, a cell line derived from murine distal respiratory epithelial cells. Shifts in subcellular distribution occurred within 5 min of exposure to 200 microM oleic acid. The magnitude of the increases in microsomal enzyme activity and immunoreactive protein levels was several-fold greater in d21 fetal cells than adult type II cells. Oleic acid-induced translocation was confirmed in in vitro translocation experiments. After incubating MLE12 cell postmitochondrial supernatants at 37 degrees C with oleic acid and separation of enzyme isoforms on glycerol density gradients, enzyme activity was decreased in gradient fractions corresponding to both cytosolic isoforms and microsomal activity increased 7.9-fold compared to the distribution of enzyme activity in postmitochondrial supernatants incubated at 4 degrees C without oleic acid. The increase in microsomal activity was associated with an increased incorporation of [14C]oleic acid in the membrane free fatty acid fraction. Developmental changes in type II cell membrane lipid composition may induce the rapid translocation/activation of cytidylyltransferase in the lung after birth.