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Biomedical subjects

G Dimitriou

Publications and source records attributed to G Dimitriou.

At least 37 records · Page 2Linked to original sources

Maximal airway pressures during crying in healthy preterm and term neonates.

Respiratory muscle strength can be assessed by measurement of maximal inspiratory (PIMAX) and maximal expiratory pressure (P(EMAX)) during crying. There are, however, relatively few data on P(IMAX) and P(EMAX) in infancy, particularly from those born preterm. Our aim was to investigate which factors influenced P(IMAX) and P(EMAX) in preterm and term infants. Forty infants, median gestational age 37 weeks (range 26-43) and birthweight 2.579 kg (range 0.956-5.180) were studied at a postconceptional age (PCA) of 38 weeks (range 32-44). None had respiratory problems. A facemask was placed firmly over the infant's mouth and nose and the infant studied during spontaneous crying. A pneumotachograph fitted snugly into the facemask and from a sideport airway pressure changes were measured. During crying, the distal end of the pneumotachograph was occluded for five breaths and at least three separate occlusions were made. The highest P(EMAX) value sustained for at least 1 s and the highest peak inspiratory pressure P(IMAX) were recorded. The mean P(IMAX) and P(EMAX) were higher in the term compared to the preterm infants (70 cmH2O +/-S.D. 19 versus 58 cmH2O +/-S.D. 17 P(IMAX) and 53 cmH2O +/-S.D. 13 versus 44 cmH2O +/-S.D. 19 P(EMAX), P< 0.05). Both P(IMAX) and P(EMAX) related significantly with postconceptional age, gestational age and weight, but not postnatal age. Stepwise regression analysis demonstrated P(IMAX) related independently with PCA and P(EMAX) with weight. These results suggest respiratory muscle strength is influenced by maturation at birth.

Airway Resistance↗

Evidence to suggest that the phosphodiesterase 4 isoenzyme is present and involved in the proliferation of umbilical cord blood mononuclear cells.

BACKGROUND: The type 4 phosphodiesterase (PDE) isoenzyme is the main isoenzyme of PDE involved in the control of adult mononuclear cell proliferation. OBJECTIVE: To establish whether PDE isoenzymes are present in umbilical cord blood mononuclear cells by the use of selective PDE inhibitors, and to identify which PDE isoenzymes are involved in controlling the proliferation of cord blood mononuclear cells. METHODS: Cord blood was obtained from normal deliveries and mononuclear cells isolated as described previously [1] with some modifications. Mononuclear cells were then stimulated to proliferate with phytohaemagglutinin (PHA) (2 microg/mL) in the presence of selective PDE inhibitors. Proliferation was measured by [3H]-thymidine incorporation. RESULTS: The type 4 PDE inhibitors (CDP840, rolipram and RO 20-1724), and the mixed PDE3/4 inhibitor, zardaverine, produced a concentration-related inhibition of PHA-stimulated cord blood mononuclear cell proliferation (P < 0.05, ANOVA). The non-selective PDE inhibitor, theophylline, also produced a concentration-related inhibition of proliferation (P < 0.05, ANOVA). In contrast, the PDE1 inhibitor, vinpocetine, the PDE3 inhibitor, siguazodan, and the PDE5 inhibitor, zaprinast, were unable to inhibit cord blood mononuclear cell proliferation. CONCLUSION: PDE4 is present in umbilical cord mononuclear cells and is involved in the control of cord blood mononuclear cell proliferation.

3',5'-Cyclic-AMP Phosphodiesterases↗

Randomized trial of two levels of fluid input in the perinatal period--effect on fluid balance, electrolyte and metabolic disturbances in ventilated VLBW infants.

The aim of this study was to determine whether fluid restriction does indeed significantly increase acute adverse effects. One-hundred-and-sixty-eight ventilated infants, median gestational age 27 wk (range 23-33) and birthweight 953 g (range 486-1500), entered into a randomized controlled trial of two fluid regimes. Infants on regime A were to be prescribed 60 ml/kg of fluids on day 1 which was gradually increased over the first week to 150 ml/kg, infants on fluid regime B were to be prescribed approximately 20% less fluid over the first week. Daily fluid input and output were recorded. Serum electrolytes, bilirubin, creatinine and urine osmolalities were measured daily. Arginine vasopressin levels were assessed on days 1, 3 and 5. Episodes of jaundice, hypoglycaemia and hypotension requiring treatment were noted. Infants on regime B actually received overall 11% and, in the first 4 days, 19% less fluid than those on regime A (p < 0.001). There were no statistically significant differences in the occurrence of episodes of jaundice, hypotension, hypoglycaemia, hypernatraemia or hyponatraemia between infants on the two regimes. Although the infants on regime B had significantly higher urine osmolalities and lower urine output for most of the perinatal period, their median creatinine and arginine vasopressin levels did not differ significantly from those on regime A. We conclude that fluid restriction to less than 90% of usual maintenance fluids is not associated with an excess of acute adverse effects.

Dehydration↗

Randomised trial of fluid restriction in ventilated very low birthweight infants.

BACKGROUND: Fluid restriction has been reported to improve survival of infants without chronic lung disease (CLD), but it remains unknown whether it reduces CLD in a population at high risk of CLD routinely exposed to antenatal steroids and postnatal surfactant without increasing other adverse outcomes. AIM: To investigate the impact of fluid restriction on the outcome of ventilated, very low birthweight infants. STUDY DESIGN: A randomised trial of two fluid input levels in the perinatal period was performed. A total of 168 ventilated infants (median gestational age 27 weeks (range 23-33)) were randomly assigned to receive standard volumes of fluid (60 ml/kg on day 1 progressing to 150 ml/kg on day 7) or be restricted to about 80% of standard input. RESULTS: Similar proportions of infants on the two regimens had CLD beyond 28 days (56% v 51%) and 36 weeks post conceptional age (26% v 25%), survived without oxygen dependency at 28 days (31% v 27%) and 36 weeks post conceptional age (58% v 52%), and developed acute renal failure. There were no statistically significant differences between other outcomes, except that fewer of the restricted group (19% v 43%) required postnatal steroids (p < 0.01). In the trial population overall, duration of oxygen dependency related significantly to the colloid (p < 0.01), but not crystalloid, input level; after adjustment for specified covariates, the hazard ratio was 1.07 (95% confidence interval 1.02 to 1.13). CONCLUSIONS: In ventilated, very low birthweight infants, fluid restriction in the perinatal period neither reduces CLD nor increases other adverse outcomes. Colloid infusion, however, is associated with increased duration of oxygen dependency.

Acute Kidney Injury↗

A comparison of arginine vasopressin levels and fluid balance in the perinatal period in infants who did and did not develop chronic oxygen dependency.

Arginine vasopressin (AVP) levels on days 1, 3 and 5 and fluid balance in the perinatal period were assessed in 60 infants, median gestational age 27 weeks (range 24-33). Fluid input and output, urine osmolality and episodes of hyponatraemia were recorded on a daily basis. Forty-one infants subsequently developed chronic lung disease (CLD), they were more immature, of lower birthweight and had higher AVP levels on days 3 and 5 (p < 0.05) than the rest of the cohort. Despite similar levels of fluid input, compared to the non-CLD infants, those who developed CLD had higher urine osmolalities on days 1, 5, 6 and 7 (p < 0.05), but there were not significant differences between the two groups regarding urine output or episodes of hyponatraemia. Logistic regression analysis revealed AVP levels on day 3 were significantly correlated with the duration of oxygen dependency independent of other factors. We conclude elevated AVP levels in the perinatal period are associated with CLD development, but our results suggest they have little functional significance.

Arginine Vasopressin↗

Assessment of neonatal diaphragm function using magnetic stimulation of the phrenic nerves.

A nonvolitional test to assess diaphragm strength in neonates has not been previously described. Our aim was to assess the feasibility of cervical (CMS) and anterior (AMS) magnetic stimulation of the phrenic nerves in neonates. Double circular stimulating coils (90-mm) were used. For CMS, one coil was placed over the cervical spine to bilaterally stimulate the phrenic nerve roots, whereas for AMS the coils were placed on the anterolateral aspect of the neck to allow unilateral and bilateral stimulation. Diaphragm contractility was assessed as transdiaphragmatic pressure (Pdi) measured with balloon catheters positioned in the midesophagus and stomach. Stimulus supramaximality was assessed by examining diaphragm twitch Pdi (TwPdi) across a range of stimulator outputs; 85, 90, 95, and 100% of maximum. Pressure signals were measured by differential pressure transducer and displayed in real time on a computer. Patients were studied supine during sleep. CMS was performed on seven neonates (mean gestational age [GA] 38 wk, range 33 to 40 wk) and AMS on 18 neonates (mean GA 37 wk, range 32 to 41 wk). The mean (SD) TwPdi with CMS was 2.5 (0.8) cm H(2)O. CMS was not supramaximal; reducing the stimulator output below 100% caused marked reductions in TwPdi, also the shape of the pressure waveforms suggested that CMS may not have activated the diaphragm alone. Mean (SD) TwPdi with AMS was 4.5 (1.3) cm H(2)O on the left, 4.1 (0.9) cm H(2)O on the right, and 8.7 (3.9) cm H(2)O for bilateral stimulation. The shape of the pressure waveforms suggested that AMS was more specific and a plateau in TwPdi at higher stimulator outputs indicated supramaximality. We conclude that AMS may provide a useful technique to assess diaphragm function in the neonate.

Diaphragm↗

Computer assisted analysis of the chest radiograph lung area and prediction of failure of extubation from mechanical ventilation in preterm neonates.

Post-extubation chest radiographs (CXRs) are frequently requested on the neonatal intensive care unit, but it is controversial whether they generate useful information. A low lung volume assessed by measurement of functional residual capacity (FRC) post extubation has been demonstrated to predict extubation failure, which is a subsequent requirement for increased respiratory support. We have previously shown that the CXR lung area obtained by computer assisted analysis significantly correlated with FRC and, therefore, speculated that a low CXR lung area post extubation would reliably predict extubation failure. The aim of this study was to test the hypothesis by analysing CXRs from 20 infants, with median gestational age of 28 weeks (range 25-33 weeks) and postnatal age 4 days (range 1-11 days). CXRs were obtained within 4 h of extubation and were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra pad and NIH image software. The cardiac, mediastinal and thymic shadows, and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. Seven infants failed extubation and differed significantly from the rest of the cohort only with regard to their CXR lung area, median gestational age, birth weight and postnatal age. Receiver operator characteristic (ROC) curves were constructed and the areas under each ROC curve were compared. Analysis demonstrated that a low CXR lung area and an older postnatal age were the best predictors of extubation failure. A post-extubation CXR lung area of < 8.5 cm2 had the highest specificity (100%) in predicting extubation failure. We conclude that routine post-extubation CXRs can have a useful role.

Birth Weight↗

The chest radiograph appearances of very premature infants at 36 weeks post-conceptional age.

The chest radiograph of very premature infants at 36 weeks post-conceptional age (PCA) was evaluated with regard to the degree of hyperinflation and cardiomegaly, and the presence of fibrosis/interstitial shadowing, cystic elements, air bronchograms and opacification. The evolution of abnormalities was assessed by comparing the radiograph appearance at 36 weeks PCA with that at 28 days post-natal age (PNA). Three scoring systems were used to determine how any abnormalities present could be best quantified to reflect disease severity as determined by chronic dependency upon supplementary oxygen status. Chest radiographs at 36 weeks PCA from 60 infants (median gestational age 26 weeks (range 24-28)) were studied. 47 infants also had radiographs at 28 days PNA. Only three infants had no chest radiograph abnormalities at 36 weeks PCA, although 24 infants were not dependent upon supplementary oxygen. The most common abnormalities were interstitial shadowing and hyperinflation, while cystic elements and cardiomegaly were rare. The radiographic appearance had deteriorated from 28 days PNA to 36 weeks PCA (p < 0.05); more infants at 36 weeks PCA were hyperinflated (p < 0.01). The chest radiograph appearances of infants who were dependent upon supplementary oxygen scored higher than those who were not (p < 0.01) using all three scoring systems. The system that assessed only the presence of interstitial shadowing, cystic elements and hyperinflation had the highest specificity in identifying oxygen dependency beyond 36 weeks PCA and had the highest area under the respective receiver operator characteristic curve. In conclusion, the majority of very immature infants have an abnormal chest radiograph appearance at 36 weeks PCA. The appearance can, however, be meaningfully scored by evaluating only three abnormalities.

Female↗

Chronic respiratory morbidity following premature delivery--prediction by prolonged respiratory support requirement?

UNLABELLED: Neonatal chronic lung disease (CLD) is usually diagnosed if an infant remains oxygen dependent beyond 36 weeks postconceptional age (PCA). Our aim was to determine whether a shorter duration of respiratory support accurately predicted subsequent respiratory morbidity. A total of 103 infants, median gestational age 29 weeks (range 23-35), were followed prospectively for 5 years. They had a birth weight of < 1500 g or, if a birth weight of between 1500 and 2000 g, had required neonatal ventilatory support. Parents completed diary cards; their child had positive symptom status if, in any one year, they coughed and/or wheezed on at least 3 days per week for a 4-week period or for at least 3 days following each upper respiratory tract infection. Subsequent respiratory morbidity, positive symptom status in years 1 and 2 or all 5 pre-school years, was related to various definitions of prolonged respiratory support: intermittent positive pressure ventilation dependence > 7 days; oxygen dependence > 28 days and oxygen dependence > 36 weeks PCA. In years 1 and 2, 25 children were symptomatic and 22 in all 5 years. The patients with subsequent respiratory morbidity were distinguished from those without by requiring longer respiratory support (P < 0.05). Logistic regression analysis demonstrated only oxygen dependence beyond 28 days was independently related to subsequent respiratory morbidity (P < 0.01). The positive predictive values and likelihood ratios (95% confidence intervals) for positive symptom status in all 5 years were for intermittent positive pressure ventilation > 7 days 35% (16-53) and 19.5 (1.01-3.76), for oxygen dependency > 28 days 42% (23-61) and 2.20 (1.45-5.02) and for oxygen dependency >36 weeks PCA 35% (13-58) and 1.67 (0.65-4.31). CONCLUSION: Oxygen dependency at 28 days of age remains a useful criterion on which to diagnose "neonatal" chronic lung disease.

Child, Preschool↗

Outcome predictors in nitric oxide treated preterm infants.

UNLABELLED: Our aim was to identify factors predictive of death in preterm infants in whom inhaled nitric oxide was administered in response to poor oxygenation (oxygenation index > or =15). Of the 23 (median gestational age 28 weeks, range 24-36) infants consecutively so treated, 15 died. Non-survival was commoner in infants with air leaks (12 of 12, P < 0.002) and/or a change in their oxygenation index of less than 30% in response to inhaled nitric oxide administration (P < 0.05). CONCLUSION: In preterm infants given inhaled nitric oxide because of poor oxygenation, a diagnosis of airleak and a lack of initial response are predictive of death.

Administration, Inhalation↗

Comparison of two inspiratory: expiratory ratios during high frequency oscillation.

UNLABELLED: The aim of this study was to compare gas exchange and volume delivery during high frequency oscillation at two frequently used inspiratory:expiratory (I:E) ratios: 1:2 and 1:1, other oscillatory settings being kept constant. A group of 13 infants with respiratory distress syndrome, median gestational age 28 weeks (range 23-36) and postnatal age 1 day (range 1-8) were studied. At the I:E ratio of 1:1 compared to 1:2 the median paCO(2) was lower, P < 0.05 (30 mmHg, range 22-47 vs 34 mmHg, range 27-46) and the volume delivered higher, P < 0.01 (2.6 ml/kg, range 1.2-5.6 vs 2.0 ml/kg, range 1.0-3.9). There was no significant difference in oxygenation levels at the two I:E ratios. In a related in vitro study, changing the I:E ratio from 1:2 to 1:1 increased the mean airway pressure by a median of 8.6% (range 2.9-28.1%). CONCLUSION: Routinely maintained longer expiratory than inspiratory times during high frequency oscillation should be discouraged.

Carbon Dioxide↗

Appropriate positive end expiratory pressure level in surfactant-treated preterm infants.

UNLABELLED: Positive end expiratory pressure (PEEP) is routinely used when ventilating preterm infants, and high levels are recommended in those with severe respiratory distress syndrome (RDS). Elevation of PEEP increases lung volume, as does surfactant administration. We postulated that in surfactant-treated infants even modest PEEP levels could result in overdistension and (CO(2)) retention. To test that hypothesis, lung volume, compliance and arterial blood gases were measured in eight preterm infants (median gestational age 28 weeks, range 26-35 weeks) at three PEEP levels. The infants, all with RDS, were studied at a median time of 18 h, (range 12-68 h) after their last dose of surfactant. Infants were routinely nursed at 3 cmH(2)O of PEEP, the PEEP level was then raised to 6 cmH(2)O or lowered to 0 cmH(2)O in random order. The new setting was maintained for 20 min; the PEEP level was then changed to the third level (0 or 6 cmH(2)O) again for 20 min. At the end of each 20-min period, lung volume, compliance and blood gases were measured. Lung volume was assessed by measuring functional residual capacity (FRC) using a helium dilution technique. Compliance was measured by relating the volume change from a positive pressure inflation maintained until no further volume change occurred to the pressure drop (peak inflating pressure PEEP). Increasing PEEP from 0 to 3 cmH(2)O and particularly to 6 cmH(2)O resulted in increases in FRC (P < 0.05), oxygenation (ns) and paCO(2) (P < 0.02). Specific compliance (compliance/FRC) (P < 0.05) and pH (P < 0.02) fell. CONCLUSION: Following surfactant treatment, relatively low levels of positive end expiratory pressure (</=3 cmH(2)O) may be appropriate.

Analysis of Variance↗

Comparison of the effect of two fluid input regimens on perinatal lung function in ventilated infants of very low birthweight.

UNLABELLED: Fluid overload worsens respiratory failure; conversely, fluid restriction has been associated with a higher survival rate without chronic lung disease. We therefore hypothesised that fluid restriction in the perinatal period might improve lung function in ventilated, prematurely born infants of very low birthweight. As a consequence, we compared in a randomised trial the effect of two fluid regimes on perinatal lung function. On one regime infants were to receive 60 ml/kg on day 1, increasing to 150 ml/kg by day 7, and on the other regime approximately 25% less fluid was to be prescribed. Lung function was assessed by measurement of functional residual capacity (FRC) and compliance. Measurements were made daily on days 1 to 5 and then on day 7. Ninety infants, median gestational age 28 weeks (range 23-33), were included in the study. There were no significant differences between the two groups regarding their gestational age or birthweight, or in the proportions who received antenatal steroids or postnatal surfactant. The infants on the restricted regime received significantly less fluid (P < 0.01). The only significant differences in lung function between the two groups, however, were that the infants on the restricted regime had a higher mean compliance on day 3, but thereafter the difference was reversed. Colloid intake, however, unfavourably affected lung function, total colloid intake being negatively correlated with both the area under the curve of birth-adjusted FRC (P=0.003) and compliance (P=0.001). CONCLUSION: We conclude that early fluid restriction appears to have very little impact on perinatal lung function.

Analysis of Variance↗

Blood pressure rhythms during the perinatal period in very immature, extremely low birthweight neonates.

The aim of this study was to investigate if blood pressure (BP) rhythms were present in the perinatal period in very immature infants. Twenty-two infants, median gestational age 24-28 weeks, who had indwelling arterial lines with undamped arterial BP waveforms, were studied. The infants were all receiving intensive care under constant conditions. The hourly mean, systolic and diastolic BPs on days 2 and 7 were examined. A cosinor analysis of the mean BP was performed examining period lengths of 4, 8, 12, 16, 20, and 24 h to determine whether ultradian and/or circadian rhythms existed. On day 2, but not day 7, the mean and systolic BPs showed significant variation and circadian and ultradian rhythms were demonstrated. We suggest that maternal influences may be responsible for the BP rhythms noted in very immature infants on day 2.

Blood Pressure↗

Prediction of prolonged ventilator dependence in children by respiratory function measurements.

Complications of ventilatory support are more common if this assistance is prolonged. Our aim was to determine if results of respiratory function measurement on the first day of ventilation identified children who would develop prolonged ventilatory dependence (> or = 4 days) and whether such results were a more accurate predictor than readily available clinical data. Thirty three children, median age 2 years (range 0.1-13.6), who were supported by a constant flow ventilator and hence had measurements of compliance of the respiratory system (CRS) and resistance of the respiratory system (RRS) on the first day of ventilatory support, were retrospectively identified. Those who needed prolonged ventilatory support had a lower CRS on day one (p < 0.01) and required at any time during their ventilatory career both a higher maximum inspired oxygen concentration (p < 0.01) and peak inspiratory pressure (PIP) (p < 0.01). Logistic regression analysis demonstrated that only a low CRS and high maximum PIP were significantly correlated with prolonged ventilator dependence. A low CRS (<0.4 (ml/cmH2O) kg(-1)) and a high maximum PIP (>27 cmH2O) had similar sensitivities (83%) and specificities (71% and 67% respectively) in predicting prolonged ventilatory dependence. The CRS results, unlike the maximum PIP results, however, were always available on the first day of ventilatory support. We therefore conclude that respiratory function measurements have a role in identifying children who would benefit from strategies to prevent prolonged ventilator dependence.

Adolescent↗

Plasma arginine levels and the response to inhaled nitric oxide in neonates.

Inhaled nitric oxide (iNO) can be an effective vasodilator in pulmonary hypertension of the newborn (PHN). The aim of this study was to determine whether differences in arginine levels, from which endogenous NO is produced, explain the variability in response to NO and whether the arginine levels were lower in term and preterm infants with PHN than in infants without PHN (controls). We prospectively studied 30 infants (17 born preterm) with clinically diagnosed PHN and treated with iNO and 22 controls (14 born preterm). Three NO levels (10, 20, 40 ppm) were administered to the PHN infants to identify that associated with maximum oxygenation. Twenty-seven infants with PHN improved following iNO and had lower arginine levels than those infants who did not respond to iNO (p < 0. 05). No significant relationship, however, was noted between the arginine levels and either the magnitude of change in the oxygenation index in response to iNO or the NO level associated with maximum oxygenation. The median plasma arginine level prior to iNO of the PHN infants was 12.5 (range 2-53) mu mol/l, but not significantly lower than that of the controls (median 24, range 3-82 mu mol/l). We conclude that differences in plasma arginine levels are unlikely to explain the variation in response to iNO and that, although arginine levels tended to be lower in infants with PHN, this is not a consistent finding in either the term or preterm infants.

Administration, Inhalation↗

A radiographic method for assessing lung area in neonates.

The aim of this study was to determine whether computer assisted analysis of lung area on the chest radiograph reliably predicted lung volume in neonates. Anteroposterior chest radiographs taken for clinical purposes were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra Pad and NIH image software. The cardiac, mediastinal and thymic densities and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. This was compared with lung volume, assessed by measurement of functional residual capacity (FRC), within 1 h of the chest radiograph being performed. 50 infants, median gestational age 30 weeks (range 24-43) were studied. Their median lung area was 11.23 cm2 (range 0.82-28.53) and lung volume 28 ml (range 3-103). The intraobserver and interobserver coefficients of repeatability of lung area were 1.0 cm2 and 1.06 cm2, respectively. Lung area correlated significantly with FRC (r = 0.60, p < 0.0001). It is concluded that computer assisted analysis of the chest radiograph lung area is a reliable method of assessing lung volume in neonates.

Functional Residual Capacity↗