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Biomedical subjects

R Hartley

Publications and source records attributed to R Hartley.

At least 37 records · Page 2Linked to original sources

Acute effects of two different doses of magnesium sulphate in infants with birth asphyxia.

The effects of two different doses of magnesium sulphate (MgSO4) were evaluated in a group of 15 full term infants with Apgar scores of < 6 at 10 minutes, studied within 12 hours of delivery. Seven infants received 400 mg/kg MgSO4 and eight received 250 mg/kg. After the larger dose, mean arterial pressure (MAP) fell by a mean of 6 mm Hg (13%) at one hour but was not significantly reduced thereafter. Respiratory depression lasted three to six hours. EEG readings and heart rate were not significantly different. Mean serum Mg2+ increased from 0.79 to 3.6 mmol/l at one hour. After 250 mg/kg MgSO4, MAP, EEG, tone and heart rate were unchanged. One infant developed transient respiratory depression. Mean serum Mg2+ rose from 0.71 to 2.42 mmol/l at one hour. MgSO4 (400 mg/kg) has an unacceptable risk of hypotension; 250 mg/kg MgSO4 was not associated with hypotension although respiratory depression can occur.

Asphyxia Neonatorum↗

Quality management: the influence of staff morale on customer focus.

Staff morale can be an indicator of an organization's progress towards developing a customer-focused culture, which is necessary for delivering quality services. While not a new concept, customer focus is the force that drives Quality Management. It is, however, only one of the essential components of quality management. The methodology for assessing staff morale and relating it to customer satisfaction in a large rural hospital is outlined and discussed. Results suggest that staff are willing to respond to the present external customer focus initiative demanded by the New South Wales Health Department, provided management plays its role in creating a work environment conducive to the delivery of satisfying services.

Attitude of Health Personnel↗

The efficacy of staff training on improving internal customer satisfaction in a rural health setting.

The NSW Health Department is 3 years into its customer satisfaction initiative. North West Health Service, one of the largest rural health districts, was among the first centres to embrace the customer satisfaction philosophy starting with compulsory training of all staff. This paper reports on changes in staff morale (internal satisfaction) as a result of that training. The data suggest that training per se has had minimal effect and argues for management development, particularly regarding leadership, rather than fiscal skills.

Community Health Services↗

Mystery shopping as a quality adjunct in public health organizations.

Public health in Australia is undergoing unprecedented emphasis on meeting customers' needs, wants and expectations. Mystery shopping, common in the commercial world, has much to offer health organizations in their push towards quality. This paper describes this inexpensive technique and reports on its use in North West Health Service, a large rural health provider. The potential exists for its widescale adoption in health to better meet customer focus objectives.

Community Health Services↗

The methylfolate axis in neural tube defects: in vitro characterisation and clinical investigation.

We have investigated various micronutrients important to folate metabolism in women with two previous neural tube defect (NTD)-affected pregnancies. Results suggest the disposition of plasma 5-methyltetrahydrofolate (5CH3-H4PteGlu) with respect to dietary intake may differ from that of the control population. It appears that to achieve a given plasma level of 5CH3-H4PteGlu, the population with a history of NTD pregnancies needs to take in more dietary folate than controls. We discuss this in the context of a potential lesion at or upstream from 5,10-methylenetetrahydrofolate reductase (MTHFR). This metabolic axis, which is responsible for the multienzymic conversion of PteGlu to 5CH3-H4PteGlu, has been investigated in a rat model using liver homogenate. The anticonvulsant drug (ACD) carbamazepine was found to inhibit the reaction in terms of a reduced Vmax and increased Km. Inhibition approaching maximal was found to occur at therapeutic levels of ACD. Various potential inhibitory sites along the methylfolate axis are considered and possible relationships to congenital malformations discussed. We describe folate and one carbon metabolism in relation to potential NTD lesion sites, not only in the light of present findings, but with respect to the published findings of other workers. Based on our hypothesis that an NTD lesion exists upstream from MTHFR, we expound how pteroylmonoglutamate supplementation may protect against NTD (i) by reducing endotoxic homocysteine and (ii) through inhibiting MTHFR (as do dihydrofolates) and thus diverting one carbon units into DNA thymine.

Animals↗

The fate of glycogen in granular tubule cells of rat submandibular glands during secretory events.

Glycogen, studied electron microscopically in granular tubule cells by means of the periodic acid-thiocarbohydrazide-silver proteinase technique, was found to be scattered abundantly throughout the cytoplasm. Parasympathetic nerve stimulation caused no detectable change in the glycogen. Degranulation of the granular tubule cells after either sympathetic nerve stimulation or cyclocytidine injection caused loss of the glycogen from the cells. Study of tubule cells undergoing secretion in the early stages after cyclocytidine injection indicated that glycogenolysis was occurring. Glycogen had reaccumulated in the cells within 24 h, before extensive reformation of the secretory granules had occurred, and remained abundant throughout the subsequent granule formation. It is concluded that glycogen provides an important source of energy during secretory degranulation of the granular tubule cells.

Ancitabine↗

Development of morphine glucuronidation in premature neonates.

In premature neonates (25-34 weeks gestation) who were given morphine intravenously during the first 24 h of life, only morphine, and morphine-3-glucuronide (M3G) were detected in plasma obtained after a 2-hour loading infusion, but morphine-6-glucuronide (M6G) could also be quantified following 24 h of continuous infusion. M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight. However, the M6G/M3G plasma concentration ratio decreased with increasing birth weight (and gestational age), thus providing the first indication in vivo of the differential development of uridinediphosphate glucuronosyltransferases in humans.

Birth Weight↗

Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase.

The natural arrest of vertebrate unfertilized eggs in second meiotic metaphase results from the activity of cytostatic factor (CSF). The product of the c-mos(xe) proto-oncogene is thought to be a component of CSF and can induce metaphase arrest when injected into blastomeres of two-cell embryos. The c-Mos(xe) protein can directly activate the mitogen-activated protein kinase kinase (MAP kinase kinase) in vitro, leading to activation of MAP kinase. MAP kinase and c-Mos(xe) are active in unfertilized eggs and are rapidly inactivated after fertilization. Microinjection of thiophosphorylated MAP kinase into one blastomere of a two-cell embryo induced metaphase arrest similar to that induced by c-Mos(xe). However, only arrest with c-Mos(xe) was associated with activation of endogenous MAP kinase. These results indicate that active MAP kinase is a component of CSF in Xenopus and suggest that the CSF activity of c-Mos(xe) is mediated by MAP kinase.

Amino Acid Sequence↗

Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies.

A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Analgesia↗

In vivo secretory responses of submandibular glands in streptozotocin-diabetic rats to sympathetic and parasympathetic nerve stimulation.

Submandibular gland responses to sympathetic and parasympathetic nerve stimulation were studied in streptozotocin-diabetic rats. Morphologically, the acinar cells in control glands were relatively uniform in size and contained electron-lucent granules. The granular ducts were distinguished by the presence of electron-dense granules. With the exception of intracellular lipid droplets and the presence of a few autophagosomes in diabetic glands, no consistent differences in acinar cell structure were observed. In contrast, the diameter of the granular ducts and the granule content of their cells were less in diabetic glands. At 3 weeks sympathetic flow rate, salivary protein concentration, and total protein output were unaffected by diabetes. Sympathetic flow rate was greater at 3 months, and the concentration of protein in the saliva was lower. In 6-month diabetic rats flow rate remained increased, but protein concentration and total protein output were reduced. The decrease in salivary protein concentration at 3 and 6 months was accompanied by a reduction in secretory granule release from acinar and granular duct cells. No consistent differences in flow rate, protein concentration, protein output, or secretory granule release were observed following parasympathetic stimulation. We conclude that the effects of diabetes on nerve-stimulated flow rate and protein release depend on the duration of diabetes and the type of stimulation, and are independent of one another.

Animals↗

Modulation of potassium evoked secretory function in rat cerebellar slices measured by real time monitoring: evidence of a possible role for methylfolate in cerebral tissue.

The real time dynamics of K+ evoked neurosecretion in cerebellar slices has been monitored electrochemically. In the presence of 5-methyltetrahydrofolate a statistically significant diminution in secretory response occurs. Agonists to probe the pharmacological basis for this indicate it is not due to voltage sensitive Ca2+ channel blockade, nor does it show any similarity of effect with kainate, whose receptor is a putative binding site for 5-methyltetrahydrofolate. The method is fully validated, although no account is taken of individual molecular species. High performance liquid chromatography combined with off line microbiological assay could only detect 5-methyltetrahydrofolate in cerebrospinal fluid. We therefore discuss our findings in relation to possible cerebral roles for cerebrospinal fluid 5-methyltetrahydrofolate in the context of both membrane and transmitter related interactions.

Animals↗

Pharmacokinetics of morphine infusion in premature neonates.

Morphine pharmacokinetics were studied in 17 premature neonates (26-34 weeks' gestation) after intravenous infusion during the first 24 hours of life. Infants received either standard dose morphine that comprised of a 100 micrograms/kg/hour loading infusion for 2 hours followed by a maintenance infusion of 12.5 micrograms/kg/hour, or a high dose of 200 micrograms/kg/hour for 2 hours followed by 50 micrograms/kg/hour. Mean plasma concentrations of morphine (SD) after 2 and 24 hours were 99 (12.9) and 96.4 (3.2) ng/ml, and 184.2 (37.7) and 319 (71.2) ng/ml for the standard and high dose regimens, respectively. Morphine-3-glucuronide plasma concentrations achieved about 20% and 80% of morphine values at 2 and 24 hours respectively. Morphine-6-glucuronide could not be detected at 2 hours, but attained 20-25% of morphine plasma concentrations by 24 hours. The population mean morphine clearance was 2.4 ml/min/kg, the elimination half life was 8.75 hours and the volume of distribution was 1.82 1/kg. High plasma concentrations of morphine appeared to be well tolerated. Although mean arterial blood pressure decreased during the first six hours of treatment, this was not statistically significant; two infants experienced transient muscle rigidity, but no evidence of seizures was noted. There appears to be no clinical advantage in using the high dose regimen.

Blood Pressure↗

Morphine glucuronidation in premature neonates.

The glucuronidation of morphine was investigated in 10 premature neonates (postnatal age < 24 h at initiation of treatment) following 24 h of therapy (2 h loading infusion, followed by a constant rate infusion). Morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) were measured in plasma obtained at 24 h in all babies. Plasma concentrations of M3G and M6G correlated significantly with morphine concentration (P < 0.01 in both cases), and with each other (P < 0.001), suggesting that the capacity for morphine glucuronidation in premature neonates is not saturated at the infusion rates used in this study. M3G/morphine and M6G/morphine plasma concentration ratios were independent of morphine infusion rates (P > 0.05) and morphine plasma concentrations (P > 0.05), providing further evidence of linear kinetics. However, M3G/morphine and M6G/morphine plasma concentration ratios increased significantly with increasing birth weight (P < 0.05 in both cases). This probably reflects increase in liver weight with increasing birth weight. Although morphine glucuronidation is deficient in premature neonates, significant concentrations of the respiratory stimulant M3G are achieved rapidly (20% of morphine plasma concentrations at 2 h). At this time, the respiratory depressant M6G could not be detected.

Birth Weight↗

Ty1-copia group retrotransposons are ubiquitous and heterogeneous in higher plants.

We have used the polymerase chain reaction to isolate fragments of Ty1-copia group retrotransposons from a wide variety of members of the higher plant kingdom. 56 out of 57 species tested generate an amplified fragment of the size expected for reverse transcriptase fragments of Ty1-copia group retrotransposons. Sequence analysis of subclones shows that the PCR fragments display varying degrees of sequence heterogeneity. Sequence heterogeneity therefore seems a general property of Ty1-copia group retrotransposons of higher plants, in contrast to the limited diversity seen in retrotransposons of Saccharomyces cerevisiae and Drosophila melanogaster. Phylogenetic analysis of all these sequences shows, with some significant exceptions, that the degree of sequence divergence in the retrotransposon populations between any pair of species is proportional to the evolutionary distance between those species. This implies that sequence divergence during vertical transmission of Ty1-copia group retrotransposons within plant lineages has been a major factor in the evolution of Ty1-copia group retrotransposons in higher plants. Additionally, we suggest that horizontal transmission of this transposon group between different species has also played a role in this process.

Amino Acid Sequence↗

Solid phase extraction of oxcarbazepine and its metabolites from plasma for analysis by high performance liquid chromatography.

A rapid, sensitive and simple-to-operate high performance liquid chromatographic method for the simulataneous determination of oxcarbazepine, 10-hydroxycarbazepine and 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine in plasma is described. The drug and its metabolites were extracted from plasma using commercially available reversed phase octadecylsilane bonded-silica columns (Bond Elut C18, 1 mL capacity). Chromatographic separation of oxcarbazepine and its metabolites was achieved using a mobile phase consisting of acetonitrile/methanol/water (13:25:62 by volume) at a flow rate of 1.2 mL/min in conjunction with a Waters Associates Nova-Pak C18 column. The analytical column, in Radial-Pak cartridge form, was used in combination with a LiChrospher 5 microns C18 guard column. By measuring the UV absorbance at 214 nm, plasma levels in the region of 50-100 ng/mL for the drug and its metabolites can be detected with only 100 microL of plasma. The method has been applied to pharmacokinetic studies of oxcarbazepine and its metabolites in children with epilepsy; preliminary pharmacokinetic findings in two patients at steady-state are presented.

Anticonvulsants↗