A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis ... more A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis has never been reported. We report the case of a 7-month-old boy born at 33 weeks gestation with a history of Down syndrome, atrial septal defect, pulmonary hypertension, and chronic lung disease, hospitalized due to RSV bronchiolitis who developed bilateral spontaneous chylothorax with exacerbation of pulmonary hypertension (PH). The patient died after 9 weeks of mechanical ventilation and treatment for PH. The autopsy showed acute infectious signs, a chronic interstitial lung disease with pulmonary hypertensive changes and subpleural cysts with no evidence of congenital lymphangiectasia. The cause of chylothorax in this child could be multifactorial. However, worsening pulmonary hypertension with RSV infection might have partially contributed to the development of chylothorax through elevated superior venous cava pressure. Thoracentesis should be considered for patients with Down syndr...
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2017
Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube pla... more Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube placement, however, can be difficult, be time-consuming, and incur multiple radiation exposures. An electromagnetic device (EMD) is available for confirmation of successful placement of TPTs. We conducted a retrospective cohort study to evaluate the efficacy of an EMD for TPT placement in children and determine its impact on placement success, radiation exposure, confirmation time, and cost for tube placement compared with traditional blind TPT placement. Retrospective data were collected in patients receiving a TPT before (pre-EMD group) and after implementation of an EMD (EMD group). Need for radiographic exposure decreased significantly in the EMD group (n = 40) compared with the pre-EMD group (n = 38) (0.6 vs 1.6 x-rays, P < .001). TPTs were placed and confirmed without abdominal x-ray in 21 of 40 patients in the EMD group. There were no serious adverse events such as misplacement in...
Background:Respiratory syncytial virus infection is the most frequent cause of acute lower respir... more Background:Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes.Methods:We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated.Results:Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients w...
American journal of physiology. Heart and circulatory physiology, Jan 15, 2018
Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe res... more Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of this study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age, and then re-infected 4 weeks later. Serum free medium was administered to age-matched mice as control. Echocardiography and right ventricular systolic pressure (RVSP) measurement via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation (SpO2) monitoring did not indicate hypoxia at 2-4 days post-RSV infection, before reinfection, and at 2-7 days after reinfection. RSV infected mice had a significantly higher RVSP than the controls. Pulsed wave Doppler r...
Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmo... more Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 3.0 with TH (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.
Our goal was to determine the factors associated with prolonged acidosis in children with diabeti... more Our goal was to determine the factors associated with prolonged acidosis in children with diabetic ketoacidosis. The records of all children (109 admissions, 86 patients) admitted to the pediatric intensive care unit (PICU) during a 3-year period with the diagnosis of diabetic ketoacidosis were analyzed. The charts were reviewed after institutional review board approval was obtained. Demographic and serial laboratory data, time to correction of acidosis, as well as the first 24-hour chloride load, total fluid administered, fluid balance, and PICU and hospital lengths of stay were recorded. The anion gap (AG = Na - Cl - HCO(3)) and the delta gap (DG = AG - 12 - [24 - HCO(3)]) were calculated. Prolonged acidosis (HCO(3) < 15 mEq/L at 24 hours) was analyzed against various independent factors on admission and during therapy. Low Na (128 vs 133 mEq/L), HCO3 (4.7 vs 9.5 mEq/L), DG (-6.3 vs -2.8 mEq/L), pH (6.97 vs 7.16), PaCO(2) (15 vs 23 mm Hg), and base excess (-26 vs -18) as well a...
The International journal of artificial organs, 2003
We carried out an experimental study to evaluate the effect of basic fibroblast growth factor (bF... more We carried out an experimental study to evaluate the effect of basic fibroblast growth factor (bFGF)-containing collagen gel on vascularization in esophageal tissue engineering. We compared an acellular collagen sponge scaffold and an acellular collagen gel scaffold in combination with bFGF using a canine model. The construct was implanted in the cervical esophagus and the regenerated tissue was evaluated one month after surgery. Histological analysis confirmed a significantly large amount of blood vessels in the bFGF-containing collagen gel group as compared to the collagen gel group without bFGF (bFGF (-)). However, in the collagen sponge groups, no difference was observed between the bFGF (+) group and the bFGF (-) group. These results showed that bFGF-containing collagen gel is suitable not only for an acellular scaffold for tissue engineering but also for an effective tropic factor vehicle in vivo.
Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome redu... more Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome. Double-blind, placebo-controlled randomized clinical trial. Le Bonheur Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital, Memphis, TN. Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation. Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects. Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects. This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.
Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmo... more Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 3.0 with TH (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.
Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hyp... more Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. Prospective randomized study. Basic research laboratory. Ten male and 10 female volunteers. Venous blood samples, taken from volunteers were cultured at 37 degrees C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s supernatant was analyzed for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interferon-gamma concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. Concentrations of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-alpha and interleukin-1beta were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-alpha and interleukin-10. Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.
We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug f... more We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug from Tinospora cordifolia, on the concentration of pro- and anti-inflammatory cytokines (interleukin [IL]-1beta, IL-6, tumour necrosis factor-alpha [TNF-alpha], gamma-interferon [IFN-gamma] and IL-10) in the lung and spleen of endotoxin-stimulated juvenile rats. Experimental groups (n = 16/group) included controls with an intraperitoneal injection of saline, endotoxaemic rats with a non-lethal dose of 10 mg/kg Escherichia coli endotoxin, and endotoxaemic rats treated with two doses of 10 mg/kg alpha-DG, intraperitoneally, 2 and 4 hr after endotoxin injection. At 24 hr of treatment, rats were euthanized and lungs and spleen were removed for cytokines determination and lung injury. Endotoxaemia increased IL-1beta concentration by fivefold in both organs, while creating a moderate pulmonary hypercellularity (demonstrated by about 11% increase in the alveolar-septal thickening and 11% decrease in the alveolar-interstitial space ratio). In the lung, alpha-DG treatment reduced concentrations of IL-1beta by 30% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05), IL-6 by 43% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), IFN-gamma by 46% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and the anti-inflammatory cytokine, IL-10, by 31% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) compared to endotoxaemia. In the spleen, alpha-DG treatment decreased the ratio of IL-1beta to IL-10 by 55% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), demonstrating an anti-inflammatory trend. These data suggest that alpha-DG differentially modulates cytokine response in the lung and spleen and modifies the pro- and anti-inflammatory balance during an early period of endotoxaemia in juvenile rats.
A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis ... more A case of bilateral spontaneous chylothorax with respiratory syncytial virus (RSV) bronchiolitis has never been reported. We report the case of a 7-month-old boy born at 33 weeks gestation with a history of Down syndrome, atrial septal defect, pulmonary hypertension, and chronic lung disease, hospitalized due to RSV bronchiolitis who developed bilateral spontaneous chylothorax with exacerbation of pulmonary hypertension (PH). The patient died after 9 weeks of mechanical ventilation and treatment for PH. The autopsy showed acute infectious signs, a chronic interstitial lung disease with pulmonary hypertensive changes and subpleural cysts with no evidence of congenital lymphangiectasia. The cause of chylothorax in this child could be multifactorial. However, worsening pulmonary hypertension with RSV infection might have partially contributed to the development of chylothorax through elevated superior venous cava pressure. Thoracentesis should be considered for patients with Down syndr...
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, 2017
Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube pla... more Transpyloric feeding tubes (TPT) are often recommended in critically ill children. Blind tube placement, however, can be difficult, be time-consuming, and incur multiple radiation exposures. An electromagnetic device (EMD) is available for confirmation of successful placement of TPTs. We conducted a retrospective cohort study to evaluate the efficacy of an EMD for TPT placement in children and determine its impact on placement success, radiation exposure, confirmation time, and cost for tube placement compared with traditional blind TPT placement. Retrospective data were collected in patients receiving a TPT before (pre-EMD group) and after implementation of an EMD (EMD group). Need for radiographic exposure decreased significantly in the EMD group (n = 40) compared with the pre-EMD group (n = 38) (0.6 vs 1.6 x-rays, P < .001). TPTs were placed and confirmed without abdominal x-ray in 21 of 40 patients in the EMD group. There were no serious adverse events such as misplacement in...
Background:Respiratory syncytial virus infection is the most frequent cause of acute lower respir... more Background:Respiratory syncytial virus infection is the most frequent cause of acute lower respiratory tract disease in infants. A few reports have suggested that pulmonary hypertension is associated with increased severity of respiratory syncytial virus infection. We sought to determine the association between the pulmonary hypertension detected by echocardiography during respiratory syncytial virus bronchiolitis and clinical outcomes.Methods:We retrospectively reviewed 154 children admitted with respiratory syncytial virus bronchiolitis who had an echocardiography performed during the admission. The association between pulmonary hypertension and clinical outcomes including mortality, intensive care unit (ICU) admission, prolonged ICU stay (>10 days), tracheal intubation, and need of high frequency oscillator ventilation was evaluated.Results:Echocardiography detected pulmonary hypertension in 29 patients (18.7%). Pulmonary hypertension was observed more frequently in patients w...
American journal of physiology. Heart and circulatory physiology, Jan 15, 2018
Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe res... more Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of this study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age, and then re-infected 4 weeks later. Serum free medium was administered to age-matched mice as control. Echocardiography and right ventricular systolic pressure (RVSP) measurement via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation (SpO2) monitoring did not indicate hypoxia at 2-4 days post-RSV infection, before reinfection, and at 2-7 days after reinfection. RSV infected mice had a significantly higher RVSP than the controls. Pulsed wave Doppler r...
Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmo... more Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 3.0 with TH (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.
Our goal was to determine the factors associated with prolonged acidosis in children with diabeti... more Our goal was to determine the factors associated with prolonged acidosis in children with diabetic ketoacidosis. The records of all children (109 admissions, 86 patients) admitted to the pediatric intensive care unit (PICU) during a 3-year period with the diagnosis of diabetic ketoacidosis were analyzed. The charts were reviewed after institutional review board approval was obtained. Demographic and serial laboratory data, time to correction of acidosis, as well as the first 24-hour chloride load, total fluid administered, fluid balance, and PICU and hospital lengths of stay were recorded. The anion gap (AG = Na - Cl - HCO(3)) and the delta gap (DG = AG - 12 - [24 - HCO(3)]) were calculated. Prolonged acidosis (HCO(3) < 15 mEq/L at 24 hours) was analyzed against various independent factors on admission and during therapy. Low Na (128 vs 133 mEq/L), HCO3 (4.7 vs 9.5 mEq/L), DG (-6.3 vs -2.8 mEq/L), pH (6.97 vs 7.16), PaCO(2) (15 vs 23 mm Hg), and base excess (-26 vs -18) as well a...
The International journal of artificial organs, 2003
We carried out an experimental study to evaluate the effect of basic fibroblast growth factor (bF... more We carried out an experimental study to evaluate the effect of basic fibroblast growth factor (bFGF)-containing collagen gel on vascularization in esophageal tissue engineering. We compared an acellular collagen sponge scaffold and an acellular collagen gel scaffold in combination with bFGF using a canine model. The construct was implanted in the cervical esophagus and the regenerated tissue was evaluated one month after surgery. Histological analysis confirmed a significantly large amount of blood vessels in the bFGF-containing collagen gel group as compared to the collagen gel group without bFGF (bFGF (-)). However, in the collagen sponge groups, no difference was observed between the bFGF (+) group and the bFGF (-) group. These results showed that bFGF-containing collagen gel is suitable not only for an acellular scaffold for tissue engineering but also for an effective tropic factor vehicle in vivo.
Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome redu... more Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome. Double-blind, placebo-controlled randomized clinical trial. Le Bonheur Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital, Memphis, TN. Children (0-18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation. Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1-7 and then tapered over days 8-14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects. Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects. This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.
Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmo... more Therapeutic hypercapnia (TH), an intentional inhalation of CO(2), has been shown to improve pulmonary function in certain models of lung injury. We tested the null hypothesis that TH does not improve hyperoxic lung injury in neonatal rats. The prospective, randomized study was set at Research laboratory in Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospital. Forty-five newborn rats were randomly assigned to three groups (n = 15/group), and exposed to 96 h of normoxia (FiO(2) = 0.21), hyperoxia (FiO(2) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.98), and TH (FiO(2) = 0.95, FiCO(2) = 0.05). Lung histology, wet-weight to dry-weight ratio, and concentrations of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IL-10) were used to evaluate pulmonary damage. Using a scale of 0-4, the total scores for lungs hypercellularity, inflammation, and hemorrhage was significantly increased from a median value of 1.5 in normoxia to 2.5 in hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and 3.0 with TH (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001, nonparametric ANOVA). The interstitial space relative to the alveolar space, as a measure of hypercellularity, was increased by 18% during hyperoxia and by 44% with TH compared with normoxia. TH significantly increased the size of the interstitial space by 22% compared with hyperoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The lung wet-weight to dry-weight ratio was increased by 10% in both hyperoxic groups (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Both hyperoxic groups showed significant reductions in the concentration of IL-1beta compared with normoxia (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), whereas the ratio of IL-1beta to IL-10 was significantly decreased, indicating an anti-inflammatory trend. TH does not prevent histological manifestations of hyperoxic lung injury in spontaneously breathing neonatal rats and may worsen the outcome.
Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hyp... more Hypercapnia is known to modulate inflammation in lungs. However, the effect of hypocapnia and hypercapnia on blood cytokine production during sepsis is not well understood. We hypothesized that CO2 modulates ex vivo inflammatory cytokine production during endotoxin stimulation. To test this hypothesis, we measured the production of pro- and anti-inflammatory cytokines in endotoxin-stimulated human whole blood cultures under hypercapnic, normocapnic, and hypocapnic conditions. Prospective randomized study. Basic research laboratory. Ten male and 10 female volunteers. Venous blood samples, taken from volunteers were cultured at 37 degrees C, under hypocapnic (2% CO2), normocapnic (5% CO2), and hypercapnic (7% CO2) conditions, with and without endotoxin stimulation. After 24 hrs of incubation, each culture&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s supernatant was analyzed for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-10, and interferon-gamma concentrations by enzyme-linked immunosorbent assay. Data were analyzed using nonparametric repeated measures of analysis of variance followed by Dunn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s multiple comparisons test. Analysis of variance with Bonferroni correction was used to compare gender differences in cytokine concentrations. The Pearson test was used to estimate correlation between hydrogen ion and individual cytokine concentrations. Concentrations of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta and of the anti-inflammatory cytokine interleukin-10 under hypercapnic condition were significantly decreased (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, 0.01, and 0.001, respectively) for both genders when compared with either normocapnic or hypocapnic conditions. Concentrations of tumor necrosis factor-alpha and interleukin-1beta were significantly higher in men. In women, concentrations of interleukin-6 were significantly decreased under hypercapnic condition when compared with hypocapnic condition. An inverse relationship was found between hydrogen ion concentration and concentrations of tumor necrosis factor-alpha and interleukin-10. Our results are consistent with the hypothesis that CO2 can affect the production of pro- and anti-inflammatory cytokines after ex vivo stimulation with endotoxin.
We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug f... more We investigated the effects of (1,4)-alpha-D-glucan (alpha-DG), a novel immune stimulatory drug from Tinospora cordifolia, on the concentration of pro- and anti-inflammatory cytokines (interleukin [IL]-1beta, IL-6, tumour necrosis factor-alpha [TNF-alpha], gamma-interferon [IFN-gamma] and IL-10) in the lung and spleen of endotoxin-stimulated juvenile rats. Experimental groups (n = 16/group) included controls with an intraperitoneal injection of saline, endotoxaemic rats with a non-lethal dose of 10 mg/kg Escherichia coli endotoxin, and endotoxaemic rats treated with two doses of 10 mg/kg alpha-DG, intraperitoneally, 2 and 4 hr after endotoxin injection. At 24 hr of treatment, rats were euthanized and lungs and spleen were removed for cytokines determination and lung injury. Endotoxaemia increased IL-1beta concentration by fivefold in both organs, while creating a moderate pulmonary hypercellularity (demonstrated by about 11% increase in the alveolar-septal thickening and 11% decrease in the alveolar-interstitial space ratio). In the lung, alpha-DG treatment reduced concentrations of IL-1beta by 30% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05), IL-6 by 43% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01), IFN-gamma by 46% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01) and the anti-inflammatory cytokine, IL-10, by 31% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 0.05) compared to endotoxaemia. In the spleen, alpha-DG treatment decreased the ratio of IL-1beta to IL-10 by 55% (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), demonstrating an anti-inflammatory trend. These data suggest that alpha-DG differentially modulates cytokine response in the lung and spleen and modifies the pro- and anti-inflammatory balance during an early period of endotoxaemia in juvenile rats.
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