ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We reviewed the 351 protocols dealing with research in infants and children in our institute between July 1982 and August 1988 to identify ethical issues that complicate the execution of pediatric research. Of the 16 rejected protocols (4.5%) 12 were drug studies, three dealt with the nature or course of disease states and one was in the area of behavioral sciences. Drug studies were significantly more likely to be rejected than all other studies. The most common reason for rejection (n= 10) were major scientific flaws that, according to the Committee, would result in inability of the study to answer the questions posed by the researchers. In nine cases the Committee judged a study to be physically invasive without a direct benefit to the involved infant/child. In three cases, the Committee rejected a study because patients with serious medical conditions might be randomized to receive placebo and not a drug that, based on current knowledge from adults, would possibly improve their condition. In three protocols, current antimicrobial therapy covered all pathogens causing the infection and the proposed new therapy could not improve the prognosis further but only be equal or inferior. Researchers who had more than one protocol rejected had significantly more protocols submitted (7.17 ± 1.35) than those who had only one rejection (1.86 ± 0.36,p< 0.0005) or than the 10 researchers with the highest number of studies without a single rejection (4.2 ± 0.4,p<0.05). These numbers suggest that scientists who perform more research are more likely to stand at the front line of unresolved ethical issues.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

It has generally been assumed that free unconjugated bilirubin gains access to the brain because of its lipid solubility. However, no measurements of the bloodbrain barrier permeability to free bilirubin exist. The aim of these experiments was to determine the blood-brain barrier permeability in the rat to free bilirubin using singlepass (Oldendorf) andin Situperfusion (Takasato) techniques. Studies were performed on adult rats under sodium pentobarbitone anesthesia. [3H]bilirubin IX-α-ZZ (sp act 6.2 Ci/mmol) was synthesized by reduction of biliverdin with sodium boro-[3H]hydride. Blood-brain barrier permeability to albumin-bound and free bilirubin was determined using injectates/perfusates containing a molar excess of human serum albumin with or without the addition of the displacing agent sulphadimethoxine. For free bilirubin, the brain uptake index was 28.5 ± 9.3 (mean ± SD,n=18), and the permeability surface area product was 54.84 ± 36.38 × 10-4mL/s/g (mean ± SD,n= 13). These results demonstrate that thebehavior of free bilirubinin vivoin relation to the cerebral microvasculature corresponds to that of a “lipid soluble” molecule.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To describe the relation between scalp blood flow and transcutaneousPO2and PCO2, these three signals were recorded simultaneously in eight experiments on four healthy lambs in the first weeks after birth. Scalp blood flow was recorded by a laser Doppler flow sensor that was incorporated in the transcutaneous PO2electrode. Scalp blood flow was varied by applying a circular pressure on the scalp surrounding the sensors. A decrease in laser Doppler blood flow was associated with a decrease in transcutaneous PO2and an increase in transcutaneous PCO2, according to a hyperbolic curve. The steep parts of the hyperbolic curves were observed at low scalp blood flow, whereas the flat parts were found at high flow values. Even during heat-induced hyperemia only a small part of these hyperbolic curves showed a reasonable independence of the transcutaneous blood gas values of changes in blood flow. In view of the previously observed decrease in intrapartum scalp blood flow, the present data render the transcutaneous measurement of blood gas values doubtful for fetal monitoring during labor.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Carbon dioxide-induced changes in near infrared spectrophotometry recordings were compared with changes in cerebral blood flow estimated by133Xenon clearance (global cerebral blood flow (infinity)) at serial measurements in 24 mechanically ventilated preterm infants (mean gestational age 30.2 wk). In all infants, three measurements were taken at different arterial carbon dioxide tension levels (mean 4.4 kPa, range 2.1-7.8) obtained by adjustment of the ventilator settings. Mean arterial blood pressure changed spontaneously, whereas arterial oxygen tension was kept within normal range. At all wavelengths (904, 845, 805, and 775 nm), the OD increased at higher arterial carbon dioxide tension levels, indicating cerebral vasodilation. This conclusion was supported by conversion of the data to changes in oxygenated and deoxygenated Hb concentration. A parallel increase in cerebral blood volume index and global cerebral blood flow (infinity) was found (P<0.0001). The oxygenation level of cytochrome aa3increased with increases in oxygen delivery (P<0.0001). This observation, however, may have been artifactual due to cross-talk between the oxidized cytochrome aa3and the oxygenated Hb signals, as these signals were closely interrelated in the present experimental design. We suggest that near infrared spectrophotometry may be used for estimation of the cerebral blood volume index/cerebral blood flow-CO2reactivity within a wide range of arterial carbon dioxide tension. Knowledge of the light path length would put this estimation on a quantitative basis.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The relationship between cerebral blood flow (CBF) and the evolution of brain edema was investigated in an experimental model of perinatal hypoxic-ischemic brain damage. Seven-d postnatal rats were subjected to unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen at 37°C. This insult produces neuronal necrosis and/or infarction only in the cerebral hemisphere ipsilateral to the arterial occlusion in the majority of animals; hypoxia alone produces no damage. CBF, measured by the indicator diffusion technique using iodo-[14C]-antipyrine, and tissue water content were determined concurrently in both cerebral hemispheres at specific intervals during recovery from cerebral hypoxia-ischemia. Water contents in the ipsilateral cerebral hemisphere were 89.1, 89.6, 89.7, 91.0, and 88.3% at 30 min, 4 h, 24 h, 3 d, and 6 d, respectively (p<0.001); whereas the percent tissue water in the contralateral hemisphere was unchanged from values in nonligated, hypoxic control rats (87.7%). CBF was similar in both cerebral hemispheres at 30 min, 4 h, and 24 h of recovery (50–65 mL/100 g/min) and not different from age-matched controls. At 3 and 6 d, CBF in the ipsilateral cerebral hemisphere was 30 and 26% of the contralateral hemisphere and 23 and 29% of the control animals, respectively (P<0.001). No inverse correlation existed between the changes in brain water content and CBF at any interval until 6 d of recovery. Thus, an early hypoperfusion does not follow perinatal cerebral hypoxiaischemia, as occurs in adults. A late hypoperfusion takes place that results from rather than causes tissue necrosis seen histologically at 15–50 h of recovery. The results suggest that therapeutic attempts to improve CBF by reducing cerebral edema after hypoxia-ischemia will not alter ultimate neuropathologic outcome.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The effect of preasphyxia blood glucose concentration on postasphyxia (PA) cerebral hemodynamics was examined in 21 newborn lambs. Glucose was unregulated in one group (n=7), and controlled throughout the study by glucose clamp in hyperglycemic (n=7) and hypoglycemic (n=7) groups. Cerebral blood flow, determined using radiolabelled microspheres, and arterial and sagittal sinus O2contents were measured at control, 5 min, 1, 2, and 4 h after resuscitation from an asphyxial insult. Preasphyxia blood glucoses were 6.48 ± 0.55 mM (mean ± SEM), 12.08 ± 0.80, and 2.66 ± 0.14 in the three study groups. In all three groups, 5 min PA cerebral blood flow was significantly increased from control. In the late period after asphyxia, the unregulated group had decreased cerebral blood flow compared with control, 53.2 ± 3.8 mL·100 g-1·min-1, mean ± SEM,P<0.01; 49.6 ± 2.0,P<0.005; 53.4 ± 3.0,P<0.01, at 1, 2, and 4 h PA, respectively,versus85.7 ± 6.9 at control, whereas both the hyper- and hypoglycemic groups did not differ significantly from control measurements. Cerebral oxygen consumption (CMRO2) was significantly decreased in all three groups 5 min PA and remained decreased in the late period after asphyxia in both the unregulated and hypoglycemic groups. In the unregulated group, CMRO2was 191 ± 14 μM·100 g-1·min-1, mean ± SEM,P<0.05; 200 ± 4; and 181 ± 10,P<0.05 at 1, 2, and 4 h, respectively, PA versus 251 ± 12 at control. In the hypoglycemic group, CMRO2was 170 ± 9 μM·100 g-1·min-1, mean ± SEM,P< 0.05; 174 ± 14,P<0.05; and 183 ± 17 at 1, 2, and 4 h PA, respectively,versus231 ± 15 at control. CMRO2did not differ from control in the hyperglycemic group at 1, 2, and 4 h PA. In our newborn lamb postasphyxia model, CMRO2was best maintained PA when the lambs were hyperglycemic before asphyxia and throughout the recovery period. To the extent that more rapid recovery of CMRO2postasphyxia is a favorable outcome, these data may have implications for clinical management.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

To assess the short-term effects of highfrequency jet ventilation (HFJV) on the neonatal lung, 28 newborn piglets were studied. Nine piglets were unventilated except during brief pulmonary measurements, nine animals were conventionally ventilated (arterial CO2tension 35-45 torr, arterial O2tension 70-80 torr) for 4 h, and 10 piglets were ventilated with HFJV for the same period. Pulmonary function was analyzed using a computerized technique and tracheobronchial aspirates were examined for biochemical indicators of lung injury; after 4 h, bronchoalveolar lavage was obtained for surfactant composition and activity, and lung sections were examined by light and electron microscopy. Results showed that HFJV provided adequate ventilation at lower inspiratory pressure compared with conventional ventilation (8.6 ± 0.3 versus 13.8 ± 1.3 cm H2O;P<0.01), while pulmonary mechanics did not vary significantly among the three animal groups. Tracheobronchial aspirates from HFJV animals had higher elastase activity versus unventilated piglets (118.5 ± 14.1 versus 57.7 ± 8.4 μg/mL;P<0.01), as well as higher albumin concentration versus unventilated animals (94.2 ± 18.7 versus 23.2 ± 6.5 μg/mL;P<0.01). In addition, there were small but statistically significant differences between all three groups in the distribution of surfactant phospholipids in bronchoalveolar lavage, although biophysical activity was normal. Scanning electron microscopy revealed flattening of Clara cells in the terminal bronchioles of HFJV animals due to loss of glycogen and secretory granules. These data indicate that despite lower peak inspiratory pressures, HFJV can cause subtle biochemical changes in lungs. Further studies are indicated to determine if these changes precede significant lung injury.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The endogenously produced cytokine, tumor necrosis factor-α (TNF-α), has been shown in adult animal models to be associated with many of the pathophysiologic effects of sepsis, including systemic hypotension and hemorrhagic necrosis. TNF-α can induce the release of various vasoactive arachidonic acid metabolites, suggesting that TNF-α may act either directly or via intermediary substances in producing its effects. The pathophysiologic role of TNF-α in neonatal sepsis, especially its potential effect on pulmonary vascular tone, is presently unknown. To assess the role of TNF-α in neonatal sepsis, 19 piglets (19 ± 5 d old) were anesthetized, intubated, paralyzed, mechanically ventilated, and catheterized to assess pulmonary and systemic vascular hemodynamics and pulmonary gas exchange. The multiple inert gas elimination technique was used to assess ventilation perfusion matching. A 30-min infusion of human recombinant TNF-α (250 μg/kg total dose) was administered to animals pretreated with either 10 mg/kg dazmegrel, a thromboxane synthase inhibitor (n=9) or placebo (n=10). TNF-α alone induced a prompt and sustained rise in pulmonary arterial pressure and pulmonary vascular resistance that continued at least for 2 h after onset of the infusion. In contrast, the animals pretreated with dazmegrel demonstrated no rise in pulmonary vascular resistance until 2 h after the onset of the infusion. Neither group of animals demonstrated a significant decline in arterial PaCO2or evidence from inert gas analysis of &OV0312;A/&OV0422; mismatching or increase in intrapulmonary shunt. We conclude that human recombinant TNF-α induces an acute and sustained elevation in Ppa and PVR without the concomitant development of hypoxemia or intrapulmonary shunt. The pulmonary hypertension is blocked acutely by the putative TxA2synthase inhibitor, dazmegrel.

ISSN:0031-3998    

出版商:OVID    

年代:1990

数据来源: OVID