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Biomedical subjects

A R Franz

Publications and source records attributed to A R Franz.

12 recordsLinked to original sources

Pulmonary administration of perfluorodecaline- gentamicin and perfluorodecaline- vancomycin emulsions.

The aim of this study was to examine pharmacokinetics and pulmonary antibiotic tissue concentrations (PATC) of gentamicin and vancomycin after intrapulmonary administration of a perfluorodecaline (PFD)-gentamicin and a PFD-vancomycin emulsion during partial liquid ventilation (PLV). PLV was initiated in 19 healthy rabbits and 18 surfactant-depleted rabbits. The animals were randomized to receive either 5 mg/kg gentamicin and 15 mg/kg vancomycin intravenously, or 5 mg/kg gentamicin intrapulmonary, or 15 mg/kg vancomycin intrapulmonary. Antibiotic plasma levels were measured after 15, 30, 45, and 60 min, and hourly thereafter. After 5 h animals were sacrificed and lungs were removed to evaluate PATC and histology. PATC were significantly higher after intrapulmonary administration of both gentamicin and vancomycin. In healthy rabbits, peak plasma concentrations were lower and 5 h plasma concentrations were higher after intrapulmonary administration, whereas plasma concentrations were not different in surfactant-depleted rabbits. There were no differences in lung histology, hemodynamics, lung mechanics, or gas exchange between the treatment groups. We conclude that during PLV, higher PATC can be achieved after intrapulmonary administration of PFD-antibiotic emulsions compared with intravenous administration of the same dose without apparent short-term adverse effects. We speculate that intrapulmonary antibiotic administration during PLV may be beneficial in treating severe pneumonia.

Animals↗

Preserved spontaneous breathing improves cardiac output during partial liquid ventilation.

The aim of this study was to examine whether preserved spontaneous breathing (SB) supported by proportional-assist ventilation (PAV) would improve cardiac output (CO) during partial liquid ventilation (PLV) in rabbits with and without lung disease if compared with time-cycled, volume-controlled ventilation (CV) combined with muscle paralysis (MP). PLV was initiated in 17 healthy rabbits and 17 surfactant-depleted rabbits using 12 to 15 ml/kg of perfluorodecaline. Both ventilatory modes, SB+PAV and CV+MP, were applied in random sequence using a crossover design. CO was measured by thermodilution. CO was significantly higher during SB+PAV than during CV+MP: 136 +/- 21 ml/kg x min (mean +/- SD) versus 120 +/- 30 ml/kg x min (p = 0.004) in healthy rabbits, and 147 +/- 19 ml/kg x min versus 111 +/- 13 ml/kg x min (p < 0.0001) in surfactant-depleted rabbits, resulting in an improved oxygen delivery. This difference was mainly caused by a larger stroke volume during SB+PAV, whereas there was little change in heart rate. In surfactant-depleted rabbits, SB+PAV resulted in improved arterial blood pressure and arterial and mixed venous pH and in a higher PaO2 at the same level of PEEP and mean airway pressure. We conclude that during PLV, CO is higher during SB+PAV than during CV+MP, resulting in an improved oxygen delivery. In surfactant-depleted rabbits, improved CO, oxygen delivery, and arterial blood pressure resulted in higher pH, possibly reflecting improved tissue perfusion and oxygenation.

Analysis of Variance↗

Interleukin-8: a valuable tool to restrict antibiotic therapy in newborn infants.

UNLABELLED: This study was conducted to evaluate the accuracy and kinetics of interleukin 8 (IL-8) as a test for early-onset bacterial infections (EOBI) in neonates and to examine whether IL-8 would allow "unnecessary" antibiotic therapy to be reduced. First, IL-8 was measured 378 times on admission, along with C-reactive protein (CRP), immature to total neutrophil ratio (IT ratio) and blood cultures, in full-term and preterm neonates with suspected EOBI. Combined culture-proven and clinical EOBI were detected on admission by the combination of IL-8 > or = 70 pg ml(-1) and/or CRP > 10 mg l(-1) with 92% sensitivity and 74% specificity. An increased IL-8 was found in 62% of the infected infants, while CRP was still normal. In a second study period, IL-8 was determined prospectively in 331 infants who presented clinical signs of EOBI or had a birth history of amniotic infection. Antibiotic therapy was restricted to those infants with suspected infection who also had an increased IL-8 and/or CRP (n = 158). Another 39 infants received antibiotics on the basis of clinical signs despite negative IL-8 and CRP. Of 150 non-infected infants in whom IT ratio, IL-8 and CRP were available, treatment would have been indicated for 93 infants based on IT ratio and/or CRP (n = 77) or clinical signs (n = 16), but was only initiated in 55 infants based on IL-8 and/or CRP (n = 28) or clinical signs (n = 27), an apparent reduction in "unnecessary" antibiotic therapy of 40%. CONCLUSION: The combination of IL-8 and CRP is a reliable test for the diagnosis of EOBI and may be helpful in enabling antibiotic therapy to be reduced in newborn infants.

Anti-Bacterial Agents↗

Partial liquid ventilation in severely surfactant-depleted, spontaneously breathing rabbits supported by proportional assist ventilation.

OBJECTIVE: We hypothesized that partial liquid ventilation (PLV) would improve oxygenation in nonparalyzed, surfactant-deficient rabbits breathing spontaneously while supported by proportional assist ventilation (PAV). This ventilation mode compensates for low pulmonary compliance and high resistance and thereby facilitates spontaneous breathing. DESIGN: Randomized trial. SETTING: University animal research facility. SUBJECTS: Twenty-six anesthetized New Zealand white rabbits weighing 2592 +/- 237g (mean +/- sd). INTERVENTIONS: After pulmonary lavage (target Pao2 <100 mm Hg on mechanical ventilation with 6 cm H2O of positive end-expiratory pressure [PEEP] and an Fio2 of 1.0), rabbits were randomized to PAV (PEEP of 8 cm H2O) with or without PLV. PLV rabbits received 25 mL/kg of perfluorocarbon by intratracheal infusion (1 mL/kg/min). Pao2, Paco2, tidal volume, respiratory rate, minute ventilation, mean airway pressure, arterial blood pressure, heart rate, pulmonary compliance, and airway resistance were measured. Evaporated perfluorocarbon was refilled every 30 mins in PLV animals. After 5 hrs, animals were killed and lungs were removed. Lung injury was evaluated using a histologic score. MAIN RESULTS: Pao2 and compliance were significantly higher in PLV rabbits compared with controls (p <.05, analysis of variance for repeated measures). All other parameters were similar in both groups. CONCLUSIONS: PLV improved oxygenation and pulmonary compliance in spontaneously breathing, severely surfactant-depleted rabbits supported by PAV. The severity of lung injury by histology was unaffected.

Analysis of Variance↗

Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary?

OBJECTIVE: To examine the number and volume of red blood cell transfusions (RBCTs) in very and extremely low birthweight infants under restrictive red blood cell transfusion guidelines without erythropoietin administration, and to compare the results with those reported in similar infants receiving erythropoietin. METHODS: From April 1996 to June 1999, all RBCTs given to infants with a birth weight of less than 1500 g were prospectively recorded. Data on RBCT combined with erythropoietin treatment and RBCT guidelines were extracted from four prospective randomised trials of erythropoietin for anaemia of prematurity. RESULTS: When the restrictive RBCT guidelines were followed, the number of RBCTs and volume transfused were similar to those reported during erythropoietin administration. CONCLUSIONS: RBCT guidelines may have a similar impact on RBCT in very low birthweight infants to the administration of erythropoietin. The effect of RBCT guidelines on RBCT frequency should be considered when evaluating the efficacy of erythropoietin administration to preterm infants.

Erythrocyte Transfusion↗

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.

Animals↗

Meconium passage in extremely low birthweight infants and its relation to very early enteral nutrition.

UNLABELLED: The aim of this study was to evaluate the correlation between the timing of the first and last meconium and feeding tolerance in the very early enteral nutrition of extremely low birthweight (ELBW) infants. Forty-one ELBW infants were fed following a standardized protocol (day 3-14). At 48 h of age bolus gavage feeding with milk was started (12 ml kg(-1) d(-1) increments, 12 meals per day). Gastric residuals up to 2 ml or up to 3 ml were tolerated in infants with a birthweight of < or = 750 g or > 750 g, respectively. No enemas or laxatives were given during the study. The impact of the time until the passage of the first (M-1) and last (M-last) meconium on the feeding volume on day 14 (V14) was evaluated by linear regression analysis. Data are presented as median (range). M-1 was 31 h (0.5-77 h), M-last was 6 d (1.4-22 d) and V14 was 99 (0-156) ml kg(-1). V14 increased with decreasing M-last (p < 0.001) but there was no correlation between V14 and M-1. V14 was 112 (0-156) ml kg(-1) if M-last was shorter than 6 d and 37 (0-147) ml kg(-1) if M-last was longer than 6 d. CONCLUSION: Rapid meconium evacuation appeared to be a key factor for the feeding tolerance of ELBW infants during the first 14 d of life. Further studies needed to investigate whether meconium passage can be accelerated and whether acceleration of the meconium passage will improve the early feeding tolerance in ELBWW infants.

Enteral Nutrition↗

Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams.

OBJECTIVES: To examine whether early enteral iron supplementation (EI) would improve serum ferritin as a measure of nutritional iron status at 2 months of age and would prevent definite iron deficiency (ID) in infants with a birth weight of <1301 g. METHODS: Infants were randomly assigned to receive enteral iron supplementation of 2 to 6 mg/kg/day as soon as enteral feedings of >100 mL/kg/day were tolerated (EI) or at 61 days of life (late enteral iron supplementation [LI]). Nutritional iron status was assessed: 1) at birth, 2) at 61 days of life, 3) when the infants reached a weight of 1.6 times birth weight, and 4) before blood was transfused at a hematocrit of <.25. ID was defined by any one of the following criteria: ferritin, <12 microg/L; transferrin saturation, <17%; or increase of absolute reticulocyte counts by >50% one week after the onset of enteral iron supplementation. Restrictive red cell transfusion guidelines were followed and all transfusions were documented. Erythropoietin was not administered. The primary outcome variables were: 1) ferritin at 61 days and 2) the number of infants with ID. RESULTS: Ferritin at 61 days was not different between the groups. Infants in the LI group were more often iron-deficient (26/65 vs 10/68) and received more blood transfusions after day 14 of life. No adverse effects of EI were noted. CONCLUSIONS: EI is feasible and probably safe in infants with birth weight <1301 g. EI may reduce the incidence of ID and the number of late blood transfusions. ID may occur in very low birth weight infants despite early supplementation with iron and should be considered in the case of progressive anemia.preterm infant, iron supplementation, iron deficiency, blood transfusion.

Drug Administration Schedule↗

Comparison of procalcitonin with interleukin 8, C-reactive protein and differential white blood cell count for the early diagnosis of bacterial infections in newborn infants.

OBJECTIVE: To evaluate procalcitonin (PCT) as a test for early diagnosis of bacterial infections (BI) in newborn infants and to compare the results of PCT with those of interleukin 8 (IL-8), C-reactive protein (CRP) and differential white blood cell count. STUDY DESIGN: PCT was prospectively measured along with IL-8, CRP and differential white blood cell counts and blood cultures in 197 newborn infants at the first suspicion of bacterial infection. PCT, IL-8, CRP and differential white blood cell counts were analyzed for sensitivity, specificity and positive and negative predictive values after receiver operating characteristic curve analysis for best thresholds. The kinetics of PCT was determined in infants with and without BI. RESULTS: Forty-six infants were diagnosed clinically as having BI, of whom 9 had BI with positive blood cultures. At a cutoff value of 0.50 microg/l, PCT detected combined culture-proved and clinical BI with a sensitivity of 57% (95% confidence interval, 41%, 71%) and a specificity of 66% (95% confidence interval, 57%, 74%). The combination of IL-8 > or =70 ng/l and/or CRP >10 mg/l achieved a sensitivity of 91% (95% confidence interval, 79%, 98%) and a specificity of 73% (95% confidence interval, 64%, 81%). PCT values of infected and not infected infants tended to rise for 24 h after initial evaluation and then decreased. CONCLUSION: The combination of IL-8 and CRP is more reliable than PCT as a test for early diagnosis of BI in newborn infants.

Bacterial Infections↗

Reduction of unnecessary antibiotic therapy in newborn infants using interleukin-8 and C-reactive protein as markers of bacterial infections.

OBJECTIVE: To examine whether the determination of interleukin 8 (IL-8) and C-reactive protein (CRP) in neonates with suspected nosocomial bacterial infection (NBI) is feasible and cost-effective in reducing antibiotic therapy. METHODS: Between April 1996 and May 1997, IL-8 was measured 260 times along with blood cultures, CRP, and immature-to-total-neutrophil (IT) ratio for suspected NBI in term and preterm neonates. All infants were retrospectively analyzed for NBI. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated for IL-8, CRP, and IT ratio. Receiver-operating characteristic curves were analyzed to determine optimal thresholds. Between June 1997 and June 1998, IL-8 was measured 215 times in newborn infants with suspected NBI and the decision to start antibiotic therapy was based on increased IL-8 and/or CRP values. A cost-effectiveness analysis was performed and sensitivity, specificity, and receiver-operating characteristic curves were reevaluated. RESULTS: At the first suspicion of NBI, the combination of IL-8 >/= 53 pg/mL and/or CRP >10 mg/L detected culture-proven NBI with 96% sensitivity. The combined culture-proven and clinical NBI were detected with 93% sensitivity and 80% specificity. The use of IL-8 reduced unnecessary antibiotic therapy for suspected NBI by 73% and was cost-effective when compared with initiating antibiotic therapy based on clinical signs alone or based on clinical signs and an increased IT ratio and/or CRP. CONCLUSIONS: The combination of IL-8 and/or CRP is a reliable and early test for the diagnosis of NBI in newborn infants. Using the combination of IL-8 and/or CRP to restrict antibiotic therapy to truly infected infants reduces unnecessary antibiotic therapy and is cost-effective.

Anti-Bacterial Agents↗

Transient glutamic acidaemia.

UNLABELLED: We report on a severely hypotrophic male twin with persistent diarrhoea and metabolic acidosis during the first 4 weeks of life, who showed a fivefold normal glutamate concentration in plasma. Further evaluation excluded major defects in amino acid metabolism and after 5 months glutamate concentrations returned to normal. Neither the dizygotic twin sibling nor the parents revealed any clinical abnormalities or acid base or amino acid disturbances. CONCLUSION: Transient glutamic acidaemia seems to be an extremely rare condition in newborn infants and appears to be without negative impact on the physical and neurological development during the first months of life.

Acidosis↗