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D M Peebles

Publications and source records attributed to D M Peebles.

At least 19 recordsLinked to original sources
PubMed2006

Ultrasound-guided injection and occlusion of the trachea in fetal sheep.

OBJECTIVES: To access the fetal sheep trachea by ultrasound-guided transthoracic injection in order to deliver gene therapy vectors or occlude the trachea with a detachable balloon. METHODS: Fetal sheep were operated on at a mean gestational age of 102 (range, 81-116) days (term = 145 days). Under ultrasound guidance, either a 20-G spinal (for vector delivery) or a 16-G Kellett (for placement of an occlusive balloon) needle was inserted via the fetal thorax into the fetal trachea. RESULTS: Using the 20-G spinal needle the trachea was accessed successfully in 33/36 fetuses, with 97% survival. Failure to inject was related to fetal position and gestational age. Blood vessel damage causing significant morbidity occurred in two fetuses (6%). Tracheal occlusion was achieved by puncturing the trachea with the 16-G needle and advancing an endoluminal balloon in three out of five attempts in a mean time of 17 (range, 16-19) min, with 100% survival. In one case, the balloon became sited within the accessory lobe bronchus and was not inflated. At postmortem examination 21 days later, all balloons remained inflated and occluded the trachea, and the lung-to-body weight ratio and airways morphometric indices were consistent with relative pulmonary hyperplasia in the obstructed lungs. CONCLUSIONS: Ultrasound-guided transthoracic tracheal puncture is a reliable technique in fetal sheep, with low morbidity and mortality. Using this technique, a detachable endotracheal balloon can be placed to provoke pulmonary growth. Advances in needle design and balloon size may improve the success rate.

Animals↗
PubMed2006

Clinically applicable procedure for gene delivery to fetal gut by ultrasound-guided gastric injection: toward prenatal prevention of early-onset intestinal diseases.

Targeting gene therapy vectors to the fetal intestinal tract could provide a novel means toward prevention of the early postnatal intestinal pathology of cystic fibrosis and other conditions, such as congenital enteropathy, that cause intestinal failure. Among these conditions, cystic fibrosis is by far the most common lethal genetic disease. It is caused by a functional absence or deficiency of the cystic fibrosis transmembrane conductance regulator and manifests in the gut as meconium ileus. Prenatal treatment of genetic disease may avoid early-onset tissue damage and immune sensitization, and may target cells that are less accessible in the adult. We investigated gene transfer to the fetal gut, using a minimally invasive injection technique. First-generation replication-deficient adenoviral vectors encoding the beta-galactosidase gene and transduction-enhancing agents were injected into the stomach of early-gestation fetal sheep (n = 8, 60 days of gestation; term, 145 days) under ultrasound guidance. Reporter gene expression was observed 2 days after injection in the villi of the gastrointestinal epithelia after 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining and beta-galactosidase immunohistochemistry of fetal tissues. Expression of beta-galactosidase, as measured by enzyme-linked immunosorbent assay, was enhanced after pretreatment of the fetal gut with sodium caprate, which opens tight junctions, and after adenovirus complexation with DEAE-dextran, which confers a positive charge to the virus. Instillation of the fluorocarbon perflubron after virus delivery resulted in tissue transduction from the fetal stomach to the colon. Using a clinically relevant technique, we have demonstrated widespread gene transfer to the fetal gastrointestinal epithelia.

Adenoviridae↗
PubMed2001

Conversion of umbilical arterial Doppler waveforms to cardiac cycle triggering signals: a preparatory study for online motion-gated three-dimensional fetal echocardiography.

To remove motion artefacts, a device was built to convert "noisy" umbilical arterial Doppler waveforms (UADWs) from an ultrasound (US) system into sharp ECG R-wave-like cardiac cycle triggering signals (CCTSs). These CCTSs were then used to gate a simultaneous (online) 3-D acquisition of sectional fetal echocardiograms from another US system. To test the conversion performance, a study was carried out in sheep fetal twins. Pulmonary arterial flow waveforms (PAFWs) from implanted probes were traced, in the meantime, to determine the reference cardiac cycle. Interference caused by running the two nonsynchronised US systems was controlled to three degrees (not-noticeable, moderate, and severe), together with high (> or = 40 cm/s) and low (< 40) flow velocities on UADWs. The conversion efficiency, assessed by the percentage of UADWs converted into CCTSs, was in the range of 83% to 100% for not-noticeable and moderate interference, and 0% to 71% for severe interference. The triggering accuracy, assessed by [(time lag mean between the onsets of PAFWs and corresponding CCTSs) -- (its 99% confidence level)] / the mean, was 90% to 96% for the not-noticeable interference high- and low-flow groups and for the moderate interference high-flow group; 19% to 93% for the moderate interference low-flow group; and from not obtainable up to 90% for the severe interference groups. The results show that UADWs can be used as a satisfactory online motion-gating source even in the presence of moderate interference. The major problems are from severe interference or moderate interference with low-flow velocity, which can be minimised/eliminated by the integration of the individual systems involved.

Animals↗
PubMed2001

Adenosine produces changes in cerebral hemodynamics and metabolism as assessed by near-infrared spectroscopy in late-gestation fetal sheep in utero.

Rises in fetal adenosine during hypoxia may have a metabolic inhibitory role that helps the fetus adapt to periods of low arterial partial pressure of oxygen (P(a)O(2)). We examined the fetal cerebral hemodynamic and metabolic responses to exogenous adenosine infusion and compared this with previous studies. Six fetal sheep at ca. 125 d gestation were instrumented under general anesthesia with catheters, flow probes, and near-infrared optodes and allowed to recover. After 3 d, adenosine was infused at a level known to reproduce fetal levels during hypoxia. Fetal hemodynamics and cerebral near-infrared spectroscopic (NIRS) variables were monitored and paired blood samples taken for oxygen delivery and consumption calculation. Fetal heart rate, mean arterial pressure, and carotid flow showed no change during adenosine infusion. Cerebral oxyhemoglobin (HbO(2)), deoxyhemoglobin (Hb), and blood volume rose, suggesting venous pooling in the brain. Cerebral cytochrome oxidase (CcO) became more oxidized, indicating reduction in electron flow down the mitochondrial electron transfer chain and, thus, a fall in metabolic rate. Blood sample analysis revealed that there was no change in oxygen delivery to the head but that cerebral oxygen consumption fell during adenosine infusion. These data indicate that fetal cerebral metabolism fell during infusion of adenosine at a level known to reproduce fetal plasma concentrations during hypoxia.

Adenosine↗
PubMed2000

Hemodynamic and metabolic responses to moderate asphyxia in brain and skeletal muscle of late-gestation fetal sheep.

The purpose of this study was to investigate metabolic and hemodynamic responses in two fetal tissues, hindlimb muscle and brain, to an episode of acute moderate asphyxia. Near-infrared spectroscopy was used to measure changes in total hemoglobin concentration ([tHb]) and the redox state of cytochrome oxidase (COX) simultaneously in the brain and hindlimb of near-term unanesthetized fetal sheep in utero. Oxygen delivery (DO(2)) to, and consumption (VO(2)) by, each tissue was derived from the arteriovenous difference in oxygen content and blood flow, measured by implanted flow probes. One hour of moderate asphyxia (n = 11), caused by occlusion of the maternal common internal iliac artery, led to a significant fall in DO(2) to both tissues and to a significant drop in VO(2) by the head. This was associated with an initial fall in redox state COX in the leg but an increase in the brain. [tHb], and therefore blood volume, fell in the leg and increased in the brain. These data suggest the presence of a fetal metabolic response to hypoxia, which, in the brain, occurs rapidly and could be neuroprotective.

Acid-Base Equilibrium↗
PubMed1998

The cerebral hemodynamic response to asphyxia and hypoxia in the near-term fetal sheep as measured by near infrared spectroscopy.

This study examined the hypothesis that the cerebrovascular response to asphyxia of the late gestation sheep fetus is characterized by an increase in cerebrovascular resistance and a fall in cerebral blood flow (CBF) rather than the fall in resistance and increase in CBF which occurs in acute hypoxemia. In eight unanesthetized late gestation fetal sheep (123- to 125-d gestation) we evaluated continuous changes in carotid blood flow (CaBF) as an index of global CBF and total cerebral Hb concentrations as an index of global cerebral blood volume (CBV) using ultrasound flow probes and near infrared spectroscopy respectively. Asphyxia was induced by rapid and complete occlusion of the umbilical cord for 10 min. We also examined the fetal response to 1 h of acute 9% isocapnic hypoxia for comparison purposes. During hypoxia we observed a sustained increase in CaBF (p < 0.05) and CBV (p < 0.01) and a fall in carotid vascular resistance (p < 0.05). During asphyxia there was no significant rise in CBV, a fall in CaBF (p < 0.05), and a rise in carotid vascular resistance (p < 0.01). CaBF fell at a time when mean arterial pressure was elevated (p < 0.01). These data strongly suggest that fetal CBF does not increase and may even fall during severe asphyxia of rapid onset. Furthermore, our near infrared spectroscopy data show that the relative changes in total cerebral Hb concentrations may reflect the type and severity of the insult to which the fetus is exposed.

Animals↗
PubMed1998

Holoprosencephaly.

Explore the source record for details and available documents.

Chromosome Aberrations↗
PubMed1997

Cerebral hemodynamics and oxygenation in the fetus. The role of intrapartum near-infrared spectroscopy.

Current methods of intrapartum surveillance have made little impact on fetal mortality and morbidity while leading to increased caesarean section rates. Near-infrared spectroscopy is a powerful new technique that can continuously measure changes in fetal cerebral oxygenation and hemodynamics during labor. Data are presented suggest that near-infrared spectroscopy has potential as a new form of fetal monitoring. However, further technical developments and testing in clinical trials are necessary before its introduction into clinical practice.

Animals↗
PubMed1995

Late fetal heart decelerations and changes in cerebral oxygenation during the first stage of labour.

OBJECTIVE: To test the hypothesis that late fetal heart rate decelerations are associated with a decrease in cerebral oxygenation. DESIGN: Changes in fetal cerebral concentrations of oxyhaemoglobin and deoxyhaemoglobin were measured by near infrared spectroscopy, before, during and after contractions with late fetal heart rate decelerations and compared with changes during contractions with no alteration of heart rate. SETTING: Teaching hospital obstetric unit. SUBJECTS: Ten women in labour at term. RESULTS: The changes in fetal cerebral oxyhaemoglobin and deoxyhaemoglobin concentrations that occurred during contractions were quantitatively similar, irrespective of the fetal heart rate changes. However, late fetal heart rate decelerations were associated with a significantly greater fall, after the uterine contraction, in the mean concentration of fetal cerebral oxyhaemoglobin of 0.52 mumol/100 g (SD 0.25) (P < 0.001) and a significantly greater rise in the mean concentration of deoxyhaemoglobin of 0.36 mumol/100 g (SD 0.35) (P < 0.01). CONCLUSION: Late fetal heart rate decelerations are associated with a significant decrease in cerebral oxygenation.

Adult↗
PubMed1995

The effect of maternal posture on fetal cerebral oxygenation during labour.

OBJECTIVE: To measure the effect of changes in maternal posture on fetal cerebral oxygenation during normal labour. DESIGN: A prospective study comparing changes in the fetal cerebral concentrations of oxyhaemoglobin, deoxyhaemoglobin and cerebral blood volume, measured by near infrared spectroscopy, in women with effective epidural analgesia when moved from the left lateral to the supine position during labour. SETTING: A London teaching hospital obstetric unit. SUBJECTS: Fourteen women during uncomplicated labour at term. RESULTS: When compared with the left lateral position, the supine position was associated with a significant decrease in the mean concentration of fetal cerebral oxyhaemoglobin of 1.12 (SD 1.0, 95% CI 0.49 to 1.75) mumol. 100 g-1 (P < 0.01) without any significant change in the mean concentration of deoxyhaemoglobin and cerebral blood volume. These changes were associated with a significant decrease in the mean cerebral oxygen saturation of 8.3 (SD 8.8, 95% CI 1.5 to 15.1)% (P < 0.05, n = 9). CONCLUSION: Changes in maternal posture during labour, in women with effective epidural analgesia, are associated with a significant decrease in fetal cerebral oxygenation.

Adult↗
PubMed1995

The effect of maternal pushing on fetal cerebral oxygenation and blood volume during the second stage of labour.

OBJECTIVE: To measure the effect of maternal pushing during the second stage of labour on fetal cerebral oxygenation and blood volume. DESIGN: A prospective study comparing changes in the fetal cerebral concentrations of oxyhaemoglobin, deoxyhaemoglobin and cerebral blood volume, before and during maternal pushing in the second stage of labour. SETTING: Teaching hospital obstetric unit. SUBJECTS: Ten term fetuses during labour. RESULTS: Following the onset of maternal pushing, mean cerebral deoxyhaemoglobin concentration increased by a mean of 0.79 (SD 0.59) mumol.100 g-1, (P < 0.01) without any consistent change in the oxyhaemoglobin concentration. These changes were associated with a significant decrease in the calculated mean cerebral oxygen saturation from a mean of 46.8% (SD 8.6) to 38.1% (SD 5.2) (P < 0.01). Pushing was also associated with a significant increase in the mean cerebral blood volume, which rose by a mean of 0.33 ml.100 g-1 (SD 0.37) (P < 0.05). CONCLUSION: Maternal pushing during the second stage of labour leads to a significant decrease in fetal cerebral oxygenation, together with an increase in cerebral blood volume.

Adult↗
PubMed1994

Relation between frequency of uterine contractions and human fetal cerebral oxygen saturation studied during labour by near infrared spectroscopy.

OBJECTIVE: To investigate the effect of the frequency of uterine contractions on fetal cerebral oxygenation, using near infrared spectroscopy. DESIGN: An observational study relating changes in the fetal cerebral concentrations of oxyhaemoglobin and deoxyhaemoglobin, measured from the start of one contraction to that of the next, to the time interval between contraction peaks observed by external tocography. SETTING: A teaching hospital obstetric and neonatal unit. SUBJECTS: Ten term fetuses during labour. RESULTS: Changes in cerebral oxyhaemoglobin concentration were positively, and in deoxyhaemoglobin negatively, correlated with the time interval between contractions (P < 0.001). A mean contraction interval of 2.3 min was found below which the concentration of oxyhaemoglobin usually fell and that of deoxyhaemoglobin rose, indicating a fall in cerebral haemoglobin saturation. Conversely, longer contraction intervals were associated with findings indicative of a rise in cerebral haemoglobin saturation. CONCLUSION: Short contraction intervals (< 2.3 min) were associated with a decrease, and longer contraction intervals with an increase in fetal cerebral oxygen saturation. Contractions occurring repeatedly at intervals less than 2.3 min are likely to result in progressive cerebral desaturation.

Brain Chemistry↗
PubMed1994

Fetal cerebral oxygenation measured by near-infrared spectroscopy shortly before birth and acid-base status at birth.

OBJECTIVE: To test the hypothesis that the mean cerebral oxygen saturation measured by near-infrared spectroscopy shortly before delivery correlates with fetal acid-base status in umbilical cord blood. METHODS: A specially designed optical probe was inserted through the dilated cervix and placed against the fetal head during labor in 41 women. Changes in cerebral oxyhemoglobin and deoxyhemoglobin concentrations were measured continuously, and the mean cerebral oxygen saturation was determined over a 10-minute period within 30 minutes of delivery. Umbilical arterial and venous blood acid-base status was assessed immediately after birth and then correlated to the values for mean cerebral saturation. RESULTS: Values for mean cerebral oxygen saturation could be determined in 33 fetuses. Umbilical cord artery and vein pH (r = 0.82 and r = 0.79, respectively) showed significant positive correlations (P < .001), whereas base deficit (r = -0.73 and r = -0.71) and carbon dioxide pressure (r = -0.68 and r = -0.63) showed significant negative correlations (P < .001) with mean cerebral oxygen saturation measured within 30 minutes before birth. There was also a significant positive correlation between umbilical vein oxygen pressure and mean cerebral oxygen saturation (r = 0.51, P < .01). CONCLUSION: Fetal umbilical blood gas and acid-base status at birth showed significant correlations with mean cerebral oxygen saturation measured shortly before delivery. Low values for saturation were related to both respiratory and metabolic acidemia.

Acid-Base Equilibrium↗
PubMed1993

Effects of N-omega-nitro-L-arginine methyl ester on the cerebral circulation of newborn piglets quantified in vivo by near-infrared spectroscopy.

The effects of N-omega-nitro-L-arginine methyl ester (L-NAME) on basal cerebral vascular tone, the vasodilatory effects of acetylcholine (ACh), and the cerebrovascular response to alterations in arterial carbon dioxide tension (CBVR) were investigated using near-infrared spectroscopy. Seven newborn piglets were anesthetized and mechanically ventilated; mean arterial blood pressure (MAP) was monitored and near-infrared spectroscopy used to measure changes in total cerebral Hb concentration. At the beginning of the experiment, CBVR was measured and then 10, 20, 30, and 100 mg.kg-1 L-NAME were administered sequentially; ACh (1, 2, 3, and 5 micrograms) was given before and after each injection of L-NAME. At the end of this sequence, CBVR was measured again and finally sodium nitroprusside (1.5 mg.kg-1) was administered. Ten and 20 mg.kg-1 L-NAME caused a significant decrease in total cerebral Hb concentration of -0.59 (-3.21 to -0.02) and -1.46 (-6.50 to -0.15) mumol.L-1 (median and range), respectively (Wilcoxon p < 0.05), but subsequent injections did not. Ten, 20, and 100 mg.kg-1 L-NAME caused an increase in MAP (Wilcoxon p < 0.05). ACh caused an increase in total cerebral Hb concentration and a decrease in MAP that was impaired but not abolished by L-NAME (ANOVA p < 0.05). CBVR was not affected by L-NAME. Sodium nitroprusside caused a reduction in mean (SD) MAP of 4.7 (1.6) kPa, and a slower rise in [tHb] of 13.44 (2.03) mumol.L-1. Postmortem examination of three animals revealed NADPH-diaphorase staining in neurons, cerebral blood vessels, carotid artery, and jugular vein.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1992

Changes in human fetal cerebral hemoglobin concentration and oxygenation during labor measured by near-infrared spectroscopy.

OBJECTIVE: The purpose of this study was to measure by near-infrared spectroscopy changes in human fetal cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume during labor and to calculate mean cerebral hemoglobin oxygen saturation. STUDY DESIGN: The effects of uterine contractions with and without fetal heart rate decelerations were compared in eight singleton term fetuses. Results were analyzed by analysis of variance. RESULTS: In six of eight fetuses normal uterine contractions were associated with proportional decreases in both oxyhemoglobin and deoxyhemoglobin and a fall in cerebral blood volume without desaturation of cerebral hemoglobin. Contractions with fetal heart rate decelerations produced different results in that oxyhemoglobin fell but deoxyhemoglobin rose, indicating cerebral desaturation. In two of the eight fetuses normal contractions were associated with increases in oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume; no decelerations were seen in either fetus. Mean cerebral hemoglobin oxygen saturation calculated during normal contractions was 43% +/- 10% (SD). CONCLUSION: Uterine contractions were associated with detectable changes from baseline in cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume.

Blood Volume↗
PubMed1992

Cerebral hemodynamic effects of treatment with modified natural surfactant investigated by near infrared spectroscopy.

The purpose of this study was to investigate the effects on cerebral hemodynamics of administering modified natural surfactant (Curosurf, 200 mg.kg-1) to infants requiring mechanical ventilation for hyaline membrane disease. Observations were made using near infrared spectroscopy on 20 infants for between 26 and 109 (median 57) min before and 22 to 112 (median 46) min after surfactant instillation. Changes in cerebral oxyhemoglobin concentration and cerebral blood volume (CBV) were monitored continuously; cerebral blood flow, oxygen delivery, and the response of CBV to changes in arterial carbon dioxide tension were measured while the infants were stable shortly before and after surfactant was given. Cerebral oxyhemoglobin concentration fell transiently in all infants immediately after surfactant by a median of -0.21 (range -0.46 to 0.05) mL x 100 g-1, but quickly recovered so that the median change during the 10 min after surfactant was 0.01 (-0.46 to 0.46) mL x 100 g-1. Alterations in CBV also occurred ranging from -0.44 to 0.40 (median 0) mL x 100 g-1, which represented -12 to 16% of total CBV; these changes rapidly resolved. When the infants were stable before and after surfactant, the values for mean (SD) cerebral blood flow were 20.5 (7.5) and 23.1 (5.2) mL.100 g-1 x min-1, respectively (n = 9); for mean cerebral oxygen delivery, values were 2.71 (0.89) and 3.15 (0.73) mL x 100 g-1 x min-1 (n = 9); and for response of CBV to changes in arterial carbon dioxide tension, they were 0.14 (0.09) and 0.11 (0.11) mL x 100 g-1 x kPa-1 (n = 16); these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗