Compensated shock and dopamine.
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Dopamine↗
Biomedical subjects
N Evans
Publications and source records attributed to N Evans.
Prostacyclin concentrations and transitional circulation in preterm infants requiring mechanical ventilation.
AIM: To describe the association between early postnatal prostacyclin concentrations in preterm infants; echocardiographic measurements of ductal diameter and ventricular output and clinical outcomes of intraventricular haemorrhage (IVH) and patent ductus arteriosus (PDA). METHODS: Forty nine preterm infants born before 30 weeks of gestational age (median birthweight 980 g, median gestational age 27 weeks) underwent echocardiographic studies at 5, 12, 24 and 48 hours of postnatal age. Measurements included ventricular outputs and the ductal shunt diameter as a measure of the shunt size. Simultaneous measurements of blood pressures, mean airway pressure and inspired fraction of oxygen (FIO2) were recorded. A blood sample for the prostacyclin metabolite 6-ketoprostaglandin F1-alpha (6KPGF1 alpha) was taken at the 5 and 24 hour echocardiogram. RESULTS: The mean 6KPGF1 alpha concentrations were higher than adult concentrations at 5 (515 pg/ml) and 24 (255 pg/ml) hours. There was no association with gestational age. Raised 6KPGF1 alpha concentrations were related to increased need for mechanical ventilation and severity of respiratory disease. At 5 hours, increased 6KPGF1 alpha concentrations were associated with larger PDA and at 24 hours with larger PDA and higher left ventricular output. Infants with higher 6KPGF1 alpha concentrations were more likely to develop clinically significant PDA. There was no association between early measurements of 6KPGF1 alpha and IVH. CONCLUSIONS: Early postnatal prostacyclin concentrations are markedly raised in preterm infants, particularly in those with more severe lung disease. Raised 6KPGF1 alpha concentrations were associated with an increased ductal diameter and subsequent PDA, but not IVH.
6-Ketoprostaglandin F1 alpha↗
Sulphur-containing amino acids are agonists for group 1 metabotropic receptors expressed in clonal RGT cell lines.
Comparison of the pharmacological effects of a range of sulphur-containing amino acids on human mGluR1alpha and mGluR5a has been undertaken. cDNAs of each mGluR were transfected into a Syrian hamster tumour cell line AV12-664 that was previously transfected with the rat glutamate-aspartate transporter protein (GLAST). The L-isomers of cysteine sulphinic acid (CSA), homocysteine sulphinic acid (HCSA), cysteic acid (CA) and serine-O-sulphate (SOS) stimulated PI hydrolysis in human mGluR1alpha and mGluR5a cells with full agonist effects. D-CSA, the only active D-isomer, was a partial agonist for mGluR5a whereas L-sulphocysteine (S-CYS) showed weak agonist-like effects at high concentrations on both mGluR1alpha and mGluR5a. L-Homocysteic acid was inactive on both mGluR1alpha and mGluR5a cells. Treatment of mGluR cultures with glutamate pyruvate transaminase did not alter the potencies of the S-amino acids on PI hydrolysis responses. Inhibitor constants (Ki) obtained for L-HCSA, L-CSA, L-CA and L-SOS in [3H]glutamate receptor binding studies with mGluR1alpha cells indicated that L-HCSA, L-CSA, L-CA and L-SOS can bind specifically to mGluR1 with L-HCSA showing the highest affinity. These results confirm that certain endogenously produced S-amino acids may interact directly with group 1 mGluRs.
Amino Acids, Sulfur↗
Should preterm infants born after 29 weeks' gestation be screened for intraventricular haemorrhage?
OBJECTIVES: To determine whether the current incidence of intraventricular haemorrhage (IVH) of grade 2 or more is high enough in preterm infants born after 29 weeks gestation to justify the cost of screening with ultrasound and to explore clinical indicators for risk of IVH in the more mature preterm infant. METHODS: This cohort study examined the incidence and severity of IVH in 800 preterm infants born between January 1992 and August 1996, of whom 436 were born after 29 weeks. Demographic and clinical details were collected from a prospectively maintained database. The Medicare schedule charge rate for cerebral ultrasound was used to calculate costs. RESULTS: 1.1% of preterm babies born after 29 weeks gestation who had routine ultrasound scans had an IVH of grade 2 or 3, no infant had a grade 4 IVH. Two infants had a grade 3 IVH, both of which were symptomatic. IVH was poorly predicted by other clinical criteria. Using the Medicare schedule to estimate costs, detecting the five grade 2 or 3 IVH cost A$42,000. CONCLUSIONS: The incidence of grade 2-4 IVH is low in infants born after 29 weeks gestation. Screening of this population is expensive and probably not justified. It may be most appropriate to scan these infants only if their condition raises concern.
Australia↗
A randomized controlled trial of two methods for collection of sterile urine in neonates.
OBJECTIVE: To test whether urethral catheterization (UC) is better than suprapubic bladder aspiration (SPA) as a method for collection of sterile urine in neonates. METHODS: Thirty-three babies, requiring sterile collection of urine, were randomly assigned to either urethral catheterization (n=16), median gestation 28+/-3.9 weeks, median birth weight 968 g (range 650-4100) or SPA (n=17), median gestation 26+/-5.6 weeks, median birth weight 926 g (range 771-4070). The primary outcome was success in obtaining urine. Secondary outcomes were complications and urine culture results. RESULTS: Some urine was obtained in 11 (64.7%) babies in the SPA group and in 13 (81.2%) babies in the catheter group. Sufficient urine for analysis (>0.5 ml) was obtained in 10 (58.8%) in the SPA group versus 5 (31.2%) babies in the catheter group. There were more contaminated specimens in the catheter group but this was not significant in this small study. CONCLUSIONS: In this small randomized controlled trial urethral catheterization offered no significant advantage over SPA.
Cystostomy↗
The persistence of hibernating myocardium after acute myocardial infarction.
OBJECTIVE: To establish the persistence of hibernating myocardium initially detected after myocardial infarction treated with thrombolysis. METHODS AND RESULTS: Fourteen patients underwent gated positron emission tomography with 18-fluoro-deoxyglucose and N13-ammonia at a median of 8 days after first myocardial infarction. Repeat scans were performed at a median of 13 weeks post-infarction. A total of 148 (30.9%) myocardial segments showed reduced N13-ammonia uptake at the time of the first scan compared with 154.5 (32.2%) segments at the time of repeat imaging. The median change in the number of segments with reduced perfusion was -1.0. Initially 13 subjects had hibernating myocardium, seven patients had large areas and six had smaller regions. Six (46.2%) subjects had repeat scans showing unchanged areas of hibernating tissue and seven had second scans demonstrating changes in the size of the region of hibernating myocardium. One patient had no hibernating myocardium on either scan. CONCLUSIONS: Positron emission tomography performed several months after myocardial infarction demonstrates significant changes in myocardial perfusion. However, a reduction in the number of segments with reduced perfusion does not always result in an improvement in myocardial metabolism and contraction. Whilst most regions of hibernating myocardium were still present several months after infarction, in only approximately half was the size of the mismatched region unchanged. Therefore it is not possible to predict the fate of hibernating myocardium which is present after infarction.
Aged↗
Range of echocardiographic findings in term neonates with high oxygen requirements.
AIMS: To examine the hypothesis that right to left shunting occurs mainly in the lungs rather than through the fetal channels in neonates. METHODS: Thirty two term babies requiring over 70% oxygen had daily colour Doppler echocardiograms until recovery. Measurements included left ventricular fractional shortening, right and left ventricular outputs, colour and pulsed Doppler ductal and atrial shunting and systolic pulmonary artery pressure (SPAP) derived from ductal shunt or tricuspid incompetence velocities. RESULTS: The babies were retrospectively classified into a respiratory group (n = 19) and a persistent pulmonary hypertension (PPHN) group (n = 13) on the basis of clinical history and radiology. At the initial echocardiogram, just 50% of babies had suprasystemic SPAP. Despite better oxygenation, more of the PPHN group had suprasystemic PAP (85% vs 26%). A correlation between SPAP and Oxygen index (OI) was present only in the respiratory group (r = 0.7). Low ventricular outputs (< 150 ml/kg/min) were common in both groups (53% and 79%). The respiratory group had more closed ducts (47% vs 0%) and those ducts which were patient were more constricted (1.75 mm vs 2.6 mm). Pure right to left ductal shunts were seen in just 15% and pure right to left atrial shunts in just 6% of all babies. The serial echocardiograms showed that SPAP fell and ducts closed well before oxygenation improved. Ventricular outputs increased with age in both groups. CONCLUSIONS: Apart from early on in the sickest babies with a primarily respiratory diagnosis and the babies with primary PPHN, most right to left shunting occurred at an intrapulmonary level.
Asphyxia Neonatorum↗
Prediction of individual response to postnatal dexamethasone in ventilator dependent preterm infants.
AIMS: To evaluate factors predictive of individual response to dexamethasone in preterm infants. METHODS: A cohort of 74 preterm infants born between January 1993 and February 1996 was studied retrospectively. All of them had received dexamethasone to facilitate weaning from artificial ventilation. Demographic factors, ventilation parameters, and details of dexamethasone administration were recorded from the medical and nursing notes. Radiographs were assessed by one observer who was unaware of the clinical condition of the infant or the outcome. Outcome variables examined included change in ventilation index (VI) at 36-48 hours, the number of days to extubation from the start of dexamethasone, and death before extubation. RESULTS: Most babies improved but changes in VI at 36-48 hours ranged from substantial deterioration to dramatic improvement. No identifiable factors were significantly associated with this range of response. The median time to extubation was 6 days. The 36 babies who extubated within the first 6 days were: significantly more mature; less likely to have pulmonary interstitial emphysema (PIE) or pneumothorax; and had significantly lower VIs in the 12 hours preceding dexamethasone treatment. The postconceptional age at extubation was the same whether babies were extubated within or after the first 6 days. Multiple linear regression confirmed a significant association between number of days to extubation and the three factors described above (adjusted R2 = 0.5126). CONCLUSIONS: Individual responses to dexamethasone can be partly predicted by gestation, the presence of PIE, and the VI before dexamethasone administration.
Dexamethasone↗
What can PACT tell us about prescribing in general practice?
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Budgets↗
YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4- benzodiazepin-3-yl]-3-(3-methylphenyl)urea]: an irreversible cholecystokinin type-B receptor antagonist.
A functional evaluation of the recently developed cholecystokinin type-B (CCK-B) receptor antagonist YM022 [(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1H-1,4-++ +benzodiazepin-3-yl]-3-(3-methylphenyl)urea] was undertaken in Chinese hamster ovary cells stably expressing the human CCK-B receptor gene (hCCK-B.CHO). YM022 exhibited high affinity and selectivity for the CCK-B receptor subtype as estimated from [125I]CCK8S displacement studies using membranes derived from hCCK-B.CHO and hCCK-A.CHO cells. Functional antagonist activity of YM022 was demonstrated employing CCK-4-stimulated Ca2+ mobilization in hCCK-B.CHO cells. In the presence of 30 nM YM022, the maximum effect of CCK-4 was suppressed to 48 +/- 11% of control, an effect that was accompanied by a modest rightward shift in the CCK-4 concentration-response curve. In contrast, the structurally similar CCK-B receptor antagonist L-365,260 [3R(+)-N-[2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin -3-yl]-N'-(methylphenyl)urea; 30 nM-10 microM] produced progressive rightward shifts in the CCK-4 concentration-response curve, with no effect observed on the CCK-4 maximum response. Further characterization using the technique of microphysiometry revealed that the agonist activity of CCK-4 was not restored following washout after exposure to YM022. The antagonist activity of L-365,260, however, was found to be fully reversible in this system. Thus, YM022 behaves as an irreversible antagonist, whilst its structural analogue L-365,260 exhibits properties consistent with a competitive antagonist.
Animals↗
Full and partial agonist activity of C-terminal cholecystokinin peptides at the cloned human CCK-A receptor expressed in Chinese hamster ovary cells.
The agonist activities of the C-terminal cholecystokinin peptides sulfated cholecystokinin octapeptide (CCK-8S), non-sulfated cholecystokinin octapeptide (CCK-8NS), pentagastrin and CCK-4 at the cloned human CCK-A receptor expressed in Chinese hamster ovary cells were evaluated in two functional assays of receptor activation. [125I]-CCK-8S displacement studies employing membranes derived from these cells revealed the expected rank order of affinity for a number of CCK receptor ligands. CCK-8S was a potent agonist in (i) stimulating the mobilization of intracellular free Ca2+, measured with the Ca2+ sensitive fluorescent indicator FURA-2, and (ii) stimulating increases in extracellular acidification rates, measured by microphysiometry. Consistent with their lower affinities for CCK-A receptors, CCK-8NS, pentagastrin and CCK-4 were weaker agonists in both functional assays. In addition, these peptides exhibited partial agonist activity relative to the maximum response observed with CCK-8S in both assays. These results demonstrate that CCK-8S represents the minimum ligand requirement for both high affinity and full agonist activity at the human CCK-A receptor subtype.
Animals↗
Multiple cerebral venous thromboses in a child with inflammatory bowel disease.
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Adolescent↗
Urinary excretion of 5-L-oxoproline (pyroglutamic acid) during early life in term and preterm infants.
Urinary 5-L-oxoproline was measured in term and preterm infants from shortly after birth until 6 weeks of postnatal age to determine their ability to synthesise glycine. In term infants the excretion was five to 10 times that seen in normal adults, increasing from 105 mumol/mmol creatinine in the first 72 hours after birth to 170 mumol/mmol creatinine at 6 weeks of age. There was a significant inverse linear correlation between the excretion of 5-L-oxoproline and length of gestation or birthweight. By 6 weeks of age there was no longer a significant difference in 5-L-oxoproline between term and preterm infants. There was no difference in the excretion of 5-L-oxoproline between boys and girls, or between infants fed on human milk or an artificial formula. If, in part, variability in the excretion of 5-L-oxoproline is determined by the extent to which the endogenous formation of glycine is adequate, then glycine formation may be marginal during early life, more so in preterm than in term infants, providing additional evidence that glycine is a conditionally essential amino acid in the neonate.
Birth Weight↗
Defining the role of the forensic community mental health nurse.
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Adult↗
Extended technicolor model with QCD-like symmetry breaking.
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Journal Article↗
Relationship between blood pressure and cardiac output in preterm infants requiring mechanical ventilation.
OBJECTIVE: To assess the contribution of cardiac output in determining the blood pressure of preterm infants and to identify other factors that may be important. METHODS: Sixty-seven preterm infants requiring mechanical ventilation (median birth weight, 1015 gm: median gestational age, 28 weeks) underwent on echocardiographic study at on average age of 19 hours (range, 7 to 31 hours). Measurements taken included left ventricular ejection fraction, left and right ventricular outputs by means of pulsed Doppler and the diameter of both the ductal and atrial shunt jets with the use of color Doppler as a measure of the size of shunt. Simultaneous measurements of intraarterial blood pressures, mean airway pressure, and inspired fraction of oxygen were recorded. RESULTS: After we allowed for the influence of ductal shunting, the correlation between the left ventricular output and mean arterial blood pressure was significant but weak (r = 0.38). There were infants with low blood pressures and normal cardiac outputs, and conversely there were infants with low cardiac outputs and normal blood pressure. The infants with a mean arterial blood pressure of less than 30 mm Hg had a significantly lower gestational age (27 vs 28 weeks), higher mean airway pressure (9.0 vs 7.0 cm H2O), larger ductal diameter (1.6 mm vs 0.7 mm) and a lower systemic vascular resistance (163 vs 184 mm Hg/L per minute per kilogram of body weight). Multilinear regression identified higher mean airway pressure and larger ductal diameter as significant negative influences on mean arterial blood pressure, with higher gestational age and higher left ventricular output as significant positive influences. CONCLUSIONS: Normal blood pressure cannot necessarily be equated with normal systemic now. These data emphasize the importance of other influences, and in particular that of varying systemic vascular resistance, in the determination of blood pressure in preterm infants.
Blood Pressure↗
Early determinants of right and left ventricular output in ventilated preterm infants.
One hundred and twenty ventilated preterm infants, birthweight < 1500 g, were examined within the first 36 hours with colour Doppler echocardiography, to determine the cardiorespiratory influences on right (RVO) and left ventricular output (LVO). Forty nine of these infants had three further daily scans. Measurements included left ventricular (LV) ejection fraction, Doppler determination of RVO and LVO, and ductal and interatrial shunt direction, velocity and colour Doppler diameter. Infants were grouped by respiratory disease severity: mild, mean FIO2 in first 24 hours < 0.5; moderate/severe, mean FIO2 < 0.5; and fatal, death resulting directly from acute respiratory distress. In the early studies ventricular outputs varied widely (RVO: 62-412 ml/kg/minute, LVO: 75-505 ml/kg/minute). The incidence of low ventricular outputs (< 150 ml/kg/minute) increased with worsening respiratory disease. The incidence of low RVO in the mild group was 19%, in the moderate/severe group 42%, and in the fatal group 85%. More infants had a low RVO than a low LVO, reflecting the impact of ductal shunting. Ductal and atrial shunting was predominantly left to right except in those with fatal respiratory disease. In those studied longitudinally, RVO and LVO increased with age and low outputs were not seen after day 3. Multilinear regression analyses, with RVO as the dependent variable, revealed increasing LVO and atrial shunt diameter as significant positive influences and increasing ductal shunt diameter and mean airway pressure as a significant negative influence. With LVO as the dependent variable, increasing RVO, ductal shunt diameter, and age were significant positive influences and increasing atrial shunt diameter was a significant negative influence. Low ventricular outputs are more common with worsening respiratory disease. Mean airway pressure and ductal shunting are two negative influences on ventricular outputs over which there is some therapeutic control.
Cardiac Output↗