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Biomedical subjects

K J Anderson

Publications and source records attributed to K J Anderson.

At least 19 recordsLinked to original sources

The cardiovascular effects of inspired oxygen fraction in anaesthetized patients.

BACKGROUND AND OBJECTIVE: Increased inspired oxygen fractions (FiO2) have significant haemodynamic effects in awake volunteers. We sought to establish whether these effects are also present in anaesthetized patients. METHODS: We prospectively studied 30 ASA I-II patients, 15 in each of a propofol and sevoflurane group. Their haemodynamic responses, awake and anaesthetized, when the FiO2 was changed between 0.3 and 1.0 were measured with a non-invasive transthoracic bio-impedance monitor. RESULTS: While preoxygenating awake patients in both groups the FiO2 was increased from 0.21 to 1.0. This reduced the mean cardiac index (3.38 +/- 0.5 to 3.03 +/- 0.5 L min(-1) m(-2); P < 0.001); reduced the heart rate (HR) (68.1 +/- 10.4 to 62.8 +/- 9.4 beats per minute (bpm); P < 0.001); and reduced the stroke index (50.4 +/- 9.6 to 48.5 +/- 8.6; P = 0.02). It increased the systemic vascular resistance index (2060 +/- 319 to 2220 +/- 382 dyn s(-1) cm(-5) m(-2); P = 0.002); but did not change mean arterial pressure. In the anaesthetized patients, when decreasing the FiO2 from 1.0 to 0.3, mean cardiac index (L min(-1) m(-2) increased (3.06 +/- 0.57 to 3.25 +/- 0.56, P = 0.008 for sevoflurane; 2.76 +/- 0.46 to 2.89 +/- 0.42, P = 0.002 for propofol). The mean HR (bpm) increased (65.1 +/- 7.8 to 69.1 +/- 7.5, P < 0.001 for sevoflurane; 67.5 +/- 11.8 to 72.7 +/- 11.6, P = 0.001 for propofol). The mean systemic vascular resistance (dyn s(-1) cm(-5) m(-2)) decreased (1883 +/- 329 to 1735 +/- 388, P = 0.008 for sevoflurane; 2015 +/- 369 to 1771 +/- 259, P = 0.003 for propofol). Mean arterial pressure (mmHg) decreased (74.8 +/- 8.7 to 71.4 +/- 8.7, P < 0.001 for sevoflurane; 72.1 +/- 8 to 66.5 +/- 6.8, P = 0.002 for propofol). CONCLUSION: O2 has haemodynamic effects in awake and anaesthetized patients. These effects were of overall similar magnitude for patients anaesthetized with propofol and sevoflurane.

Adolescent↗

Effect-site controlled patient maintained propofol sedation: a volunteer safety study.

Effect-site concentration is a mathematical term related to the clinical effect of a drug. We have designed a patient-maintained sedation system for delivering propofol to the predicted effect-site concentration rather than plasma concentration. To assess its efficacy and safety, 20 healthy volunteers deliberately attempted to over-sedate themselves using the system. The new effect-site concentration driven system delivered sedation successfully, and more rapidly than its predecessor. Fifteen volunteers ended the study when the system automatically reduced the effect-site concentration after 6 min of no button presses despite verbal contact and maintenance of arterial oxygen saturation (at effect-site concentration 1.8-3.8 microg x ml(-1)). Four out of 20 volunteers ended with minor arterial desaturation (lowest 88% at effect-site concentration 2.6-3.4 microg x ml(-1)). One volunteer ended after loss of verbal contact at effect-site concentration 3.4 microg x ml(-1). Further modification of the system's design is necessary before it can be recommended for routine practice.

Adult↗

The effect of normobaric hyperoxia on cardiac index in healthy awake volunteers.

Fifteen healthy volunteers were exposed to a stepwise increase in FIO2 between 0.21 and 1.0, and their haemodynamic responses were measured with a non-invasive transthoracic bio-impedance monitor. There was mean reduction in cardiac index from 3.44 to 3.08 l.min-1.m-2 (10.7%, p < 0.001). The mean reduction in heart rate was from 77.3 to 69.1 beats.min-1 (10.5%, p < 0.001) and the mean systemic vascular index increased from 2062 to 2221 dyne.s-1.cm-5.m-2 (7.7%, p < 0.025). There were no significant changes in stroke index or mean arterial pressure. These changes are similar quantitatively and qualitatively to those previously reported by dye dilution techniques.

Adult↗

The effect of single use laryngoscopy equipment on illumination for tracheal intubation.

We measured the illumination generated by all 30 Macintosh size 3 laryngoscopes in our department with a lux-meter and a standardised laryngoscope holding tube. We found a large range in illumination generated (65-3130 lx). We then measured the effect on the illumination for each laryngoscope by covering the blade with a cover (LaryGard). In every case, the illumination was reduced by the LaryGard, the mean (SD) reduction was 67 (19)%. When we compared the illumination generated by a disposable laryngoscope blade with the same power source, we found that the illumination was reduced less than with the standard Macintosh covered by a LaryGard.

Cross Infection↗

Ontogeny and localization of the neutral amino acid transporter ASCT1 in rat brain.

ASCT1 is a protein that encodes System ASC, a sodium-dependent amino acid transport activity that transports primarily zwitterionic amino acids at physiological pH. ASCT1 has a 39-44% identity to the EAAT family of glutamate transporters. At extracellular pH values below 7.4, ASCT1 shifts substrate specificity to transport anionic amino acids. In this study we have examined the location of the ASCT1 transporter by immunohistochemistry in the developing rat brain. In addition, we have examined the cellular localization of ASCT1 in glial and neuronal cultures. The presence of ASCT1 immunoreactivity (ASCT1ir) in the developing brain was detectable as early as 14 days of gestation. At the cellular level, ASCT1ir was prominent in hippocampal pyramidal and dentate granule neurons. In the cerebellum, Purkinje cells and their dendrites were intensely labeled, whereas the granule and molecular layers were moderately labeled. In the cerebral cortex, neuronal cell bodies in all lamina and scattered astrocytes showed intense ASCT1ir. Double labeling experiments in vitro confirmed that ASCT1 was localized to both glia and neurons. These data illustrate that the rat ASCT1 transporter is expressed in the developing brain at levels equivalent to those observed in adult tissue. In addition, the expression and localization of ASCT1 are consistent with its possible role in pathophysiological processes that involve glutamate toxicity.

Amino Acid Transport System ASC↗

An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability.

A wealth of indirect data suggest that the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development-related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218-like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218(-/-) mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole-cell patch-clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability.

Action Potentials↗

Internet use among college students: an exploratory study.

The author and associates surveyed 1,300 college students in classrooms at eight academic institutions to identify how the students' use of the Internet has affected their social or academic lives. Although the typical Internet-using student uses the Internet for 100 minutes per day, a small group of students use the Internet to a degree that interferes with other aspects of their lives. Most of them are men and are found among the hard science academic majors. Some ideas for dealing with this problem are suggested.

Adult↗

Absence of physiological tolerance to cocaine in pregnant sheep.

OBJECTIVE: To determine whether repetitive administration of cocaine to sheep during pregnancy altered basal hemodynamic states in the mother and fetus, and to determine whether this cocaine exposure would alter subsequent hemodynamic responses to cocaine. METHODS: Cocaine or saline was administered to 16 pregnant sheep daily from day 75 to day 128 of gestation (term = 145 days). At 128 days' gestation, maternal and fetal basal physiological measurements, including organ-specific blood flow in the fetus, were determined. Each experimental and control ewe then received cocaine 2 mg/kg and these physiological parameters were again measured over the next 30 min to determine whether the experimental animals had developed tolerance to the effects of cocaine. RESULTS: No differences were seen in basal physiological parameters between treatment groups. Likewise, following an acute administration of cocaine, physiological parameters in both groups responded in a similar fashion. Fetal hypoxemia occurred in both groups after the ewe received cocaine. In response to hypoxemia, whether it was the animals' first or 53rd exposure to cocaine, fetal cerebral, myocardial and adrenal blood flow increased so that oxygen delivery was unimpaired. CONCLUSIONS: For the cardiovascular parameters measured in this study, we found no tolerance to cocaine in the ewe or fetus. The acute hemodynamic effects of maternal cocaine administration were as severe for animals having received it more than 50 times as for those that received it for the first time.

Animals↗

Walnut polyphenolics inhibit in vitro human plasma and LDL oxidation.

Recent epidemiologic studies have associated nut consumption with a reduced incidence of cardiovascular mortality. However, little is known about the contribution of nut polyphenols to antioxidant and cardiovascular protection. In this investigation, polyphenol-rich extracts from English walnuts (Juglans regia) were studied and compared with ellagic acid for their ability to inhibit in vitro plasma and LDL oxidation, as well as their effects on LDL alpha-tocopherol during oxidative stress. In addition, the Trolox equivalent antioxidant activity (TEAC) was determined and liquid chromatography electrospray detection mass spectrometry (LC-ELSD/MS) analyses of the walnut extracts were performed. 2,2'-Azobis'(2-amidino propane) hydrochloride (AAPH)-induced LDL oxidation was significantly inhibited by 87 and 38% with the highest concentration (1.0 micromol/L) of ellagic acid and walnut extract, respectively. In addition, copper-mediated LDL oxidation was inhibited by 14 and 84% in the presence of ellagic acid and walnut extract, respectively, with a modest, significant LDL alpha-tocopherol sparing effect observed. Plasma thiobarbituric acid reacting substance (TBARS) formation was significantly inhibited by walnut extracts and ellagic acid in a dose-dependent manner, and the extracts exhibited a TEAC value greater than that of alpha-tocopherol. LC-ELSD/MS analysis of the walnut extracts identified ellagic acid monomers, polymeric ellagitannins and other phenolics, principally nonflavonoid compounds. These results demonstrate that walnut polyphenolics are effective inhibitors of in vitro plasma and LDL oxidation. The polyphenolic content of walnuts should be considered when evaluating their antiatherogenic potential.

Adult↗

Elimination of cocaine by pregnant sheep following single or multiple exposures.

To test the hypothesis that chronic exposure to cocaine would alter drug elimination in pregnant and fetal sheep compared to a single exposure, we administered intravenous cocaine HCl to 8 pregnant sheep daily as a bolus, followed by a 2-h infusion beginning at gestational age 75 days. Eight additional animals received an equivalent volume of saline. Three days after maternal and fetal catheter placement on day 125, ewes in both groups received cocaine HCl, 2 mg/kg, as a bolus. Maternal and fetal plasma samples were serially obtained and analyzed for cocaine and benzoylecognine. Cocaine half-life in the ewes and fetuses exposed to cocaine was no different from that in animals exposed to saline. We conclude that cocaine is rapidly metabolized in pregnant sheep and that chronic administration does not alter drug clearance.

Animals↗

Isolation and curing of the Klebsiella pneumoniae large indigenous plasmid using sodium dodecyl sulphate.

The ability of Klebsiella pneumoniae (NCTC, CL687/80) to produce and, in turn, excrete glutamate has been equated with the presence of a large indigenous plasmid with an apparent molecular mass in the region of 96 +/- 2 kbp (n = 6). Unlike mitomycin C, novobiocine and ethidium bromide (curing agents), the use of sodium dodecyl sulphate (SDS) proved very effective in curing the plasmid with a relatively high frequency (6.25 x 10(-4)). Furthermore, the absence of isocitrate dehydrogenase (ICDH) activity in the cured strain strongly suggests that the structural gene encoding ICDH in this organism, in sharp contrast to all known ICDHs, is plasmid-encoded. Moreover, the SDS-based protocol reported for the isolation of the K. pneumoniae indigenous plasmid has proven successful with other organisms including Pseudomonad and Corynebacteria, as well as in recombinant strains of Escherichia coli.

Colony Count, Microbial↗

Failed intubation in a parturient with spina bifida.

We describe a case of unexpected difficult intubation and ventilation during induction of general anaesthesia for caesarean section. This case was particularly challenging as the parturient suffered with particularly severe cord tethering following surgery for spina bifida as a child. The observed change in anticipated intubation difficulty during pregnancy, and the use of the laryngeal mask airway as a life-saving device in obstetrics are described. Consideration of the difficulties of anaesthetising the patient with spina bifida for caesarean section in general, and the issues relevant in deciding whether to continue with surgery or to wake the patient up in particular are discussed. Suggestions are made for the management of this emergency situation in those not skilled in fibreoptic intubation.

Journal Article↗

The ontogeny of glutamate receptors and D-aspartate binding sites in the ovine CNS.

The ontogeny of ligand binding to N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) receptors and to the high affinity, sodium-dependent D-aspartate binding site in prenatal and postnatal ovine brains was studied using quantitative in vitro autoradiography. In general, the binding density for each of the excitatory amino acid receptors peaked during late prenatal and early postnatal development. In contrast, binding density for D-aspartate remained low during late prenatal and early postnatal development and peaked in the adult. These data suggest that an excess number of excitatory amino acid receptors and/or a relative deficiency of transporters may make the immature brain more vulnerable to the pathologic effects of glutamate and other related excitatory amino acids.

Aging↗

Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy.

Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of neurotrophic factors and corresponding receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary neurotrophic factor receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary neurotrophic factor receptor alpha in axotomized sciatic motor neurons. Ciliary neurotrophic factor receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary neurotrophic factor receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary neurotrophic factor receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary neurotrophic factor receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary neurotrophic factor receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary neurotrophic factor receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of ciliary neurotrophic factor receptor alpha protein in response to injury. Moreover, they suggest that the ability of a subpopulation of spinal motor neurons to regulate ciliary neurotrophic factor receptor alpha levels in response to injury may play a role in their survival and axonal regeneration. Consistent with such a role, we also find relatively high, and probably elevated, levels of ciliary neurotrophic factor receptor alpha immunoreactivity in regenerating axons.

Animals↗

Glutamate receptors in the cingulate cortex, hippocampus, and cerebellar vermis of alcoholics.

This study tests the hypothesis that glutamate receptors are altered in the brains of alcoholics as a result of chronic alcohol neurotoxicity. Excessive release of the excitatory neurotransmitter glutamate may damage postsynaptic neurons by increasing calcium flux through N-methyl-D-aspartate (NMDA) receptor-gated ion channels. Alcohol has opposite effects on the NMDA receptor, depending on the duration of exposure. Acute exposure to alcohol inhibits ion flow through NMDA receptors, whereas chronic exposure upregulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of upregulated NMDA receptors, making postsynaptic neurons vulnerable to excitotoxic damage. For this study, 13 grossly and histologically normal brains from alcoholics and 13 brains from nonalcoholic controls were selected from our brain bank. The two groups were matched for age, postmortem interval, and storage time. Maximal binding and affinities of NMDA receptors were determined by quantitative autoradiography in the cingulate cortex, the cornu Ammonis of the hippocampus, and in the cerebellar vermis. Binding was determined with an agonist, L-[3H]glutamate, with a competitive antagonist, [3H]CGP-39653, and with an antagonist binding in the channel interior, [3H]MK-801. No significant differences were found in receptor densities or affinities between alcoholics and controls. Real differences were not likely to be obscured by nonalcohol-related variables because the groups were closely matched for age, autopsy delay, time in storage, and central nervous system medications. Various diseases causing acute and chronic hypoxia did not significantly affect receptor density or affinity. Liver diseases and thiamine deficiency were excluded. A long-lasting upregulation of the number or affinity of NMDA receptors is not a key feature of chronic alcoholics.

2-Amino-5-phosphonovalerate↗

Moderators of gender effects on parents' talk to their children: a meta-analysis.

Two sets of meta-analyses of studies examining gender effects on parents' observed language with their children were conducted. One looked at studies comparing mothers and fathers in amount of talking, supportive speech, negative speech, directive speech, informing speech, and questions and requests. The other looked at studies comparing mothers' interactions with daughters versus with sons in amount of talking, supportive speech, and directive speech. Across studies, mothers tended to talk more (d = .26), use more supportive (d = .23) and negative (d = .13) speech, and use less directive (d = .19) and informing (d = .15) speech than did fathers. Also, mothers tended to talk more (d = .29) and use more supportive speech (d = .22) with daughters than with sons. Medium or large effect sizes occurred in most analyses when particular moderator variables were taken into account. Effect sizes varied, depending on aspects of the interactive setting, the child's age, sampling and measurement, and publication characteristics. The results are interpreted in relation to a contextual-interactive model of gender typing.

Child↗