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Biomedical subjects

R Griffiths

Publications and source records attributed to R Griffiths.

At least 109 records · Page 6Linked to original sources
PubMed1994

Day surgery--how much is possible? A Delphi consensus among surgeons.

Although day surgery (DS) has been performed for many years, it has only relatively recently become a popular and acceptable method of treating many common surgical conditions. With considerable pressure to maximise resource usage DS has been seized upon as a way of stretching scarce resources further. A review of the amount of DS undertaken within the West Midlands region revealed that the current workload showed considerable variation both between districts and between consultants. In an effort to gain clinical commitment to increasing generally the amount of DS undertaken, and obtaining more uniform coverage of DS across the region, a consensus conference was held. The two aims of the conference were to set targets as to the amount of DS considered feasible at a procedural level, and to seek clinicians' views as to the obstacles to developing the service. Targets for 43 procedures at one and/or five years were obtained by the use of a modified Delphi consensus. The groups showed a high level of consensus in the targets reached. A variety of obstacles were discussed. We have shown that it is possible to involve a large number of doctors in the decision-making/target-setting process by using a modified Delphi technique. It remains to be seen whether those targets are met in clinical practice. Surprisingly, obstacles to development were mainly concerned with management and personnel issues rather than capital investment.

Ambulatory Surgical Procedures↗
PubMed1994

Choline acetyltransferase activity of rat synaptosomes is sensitive to enflurane, but not halothane or isoflurane.

We have examined the activity of choline acetyltransferase (ChAT) in rat cortical synaptosomes in the presence of three volatile anaesthetic agents: enflurane, halothane and isoflurane. The Michaelis constant Km, for choline was reduced significantly (P = 0.012) in the presence of 6.5% enflurane (3 rat MAC) compared with control samples exposed to carrier air only, while maximum reaction velocity (Vmax) remained unaltered. The reduction in Km was also significant at enflurane concentrations of 4.4% (2 rat MAC) (P = 0.043) and 2.2% (1 rat MAC) (P = 0.043). Halothane 3% (2.5 rat MAC) and 4.5% isoflurane (3 rat MAC) had no effect on either kinetic property. If present in vivo, an enflurane-induced alteration in acetylcholine metabolism, through modified ChAT, may contribute to the convulsive properties of this anaesthetic.

Anesthetics↗
PubMed1994

Volatile anesthetic agents inhibit choline uptake into rat synaptosomes.

BACKGROUND: Acetylcholine is an excitatory neurotransmitter associated with the maintenance of consciousness. Choline uptake is the rate-limiting step in acetylcholine synthesis and may be a target for the action of volatile anesthetic agents. METHODS: [Methyl-3H]choline uptake was investigated using rat cortical synaptosomes. The preparation was exposed to air, as control, or equipotent partial pressures (2.4 rat MAC) of enflurane, halothane or isoflurane. In addition, the dose-response relation for halothane on [methyl-3H]choline uptake was studied. RESULTS: The maximum rate of uptake was reduced significantly by 24% in the presence of enflurane (5.5%, 2.4 rat MAC) and isoflurane (3.5%, 2.4 rat MAC) and by 38% in the presence of halothane (3%, 2.4 rat MAC) with no change in Michaelis constant in the presence of each agent. A linear relation between the inhibition of [methyl-3H]choline uptake and the concentration of halothane was observed up to 3% halothane above which there was no further inhibition. The concentration of halothane resulting in half-maximum inhibition of total choline uptake was 1.5%. CONCLUSIONS: Noncompetitive inhibition of [methyl-3H]choline uptake by volatile anesthetic agents has been demonstrated in the in vitro synaptosome preparation. If present in vivo reduction in anesthetic-sensitive choline uptake may reduce the presynaptic availability of acetylcholine and hence contribute to the process of anesthesia.

Anesthetics↗
PubMed1993

The isolation of molecular genetic markers for the identification of sex.

It is difficult to identify sex in many species of eukaryotic organism. This can considerably impede research into their biology. Fortunately, one sex often possesses a unique chromosome termed Y or W. When DNA markers are available for these chromosomes, then sex identification becomes straightforward. We describe a technique that facilitates the isolation of such markers. The procedure makes use of low-stringency PCR to screen randomly selected primers for their ability to amplify sex-specific loci.

Animals↗
PubMed1993

Improved renal function in mouse kidney allografts lacking MHC class I antigens.

The immunological responses that lead to rejection of organ and tissue transplants are triggered by the recognition of proteins encoded within the MHC. The relative contributions of responses directed toward MHC class I compared with class II in the loss of functional integrity of vascularized organ grafts have been difficult to define. The recent development of technologies which allow the generation of mice in which specific genes have been altered by gene targeting offers a new approach to addressing this question. We examine here the rejection of kidney allografts from mice lacking native MHC class I Ag. These mice were obtained from embryonic stem cells in which the beta 2 microglobulin (beta 2m) gene had been disrupted by homologous recombination. We found a significant improvement in function of renal allografts from MHC class I-deficient donors compared with allografts from donors with normal MHC class I expression. Surprisingly, the improved function of the MHC class I-deficient grafts was not associated with differences in mononuclear inflammatory cell infiltration of these grafts nor in differences in alloreactive proliferative or cytotoxic T cell responses. However, we did find differences in alloantibody response between the groups. Recipients of control allografts produced antibodies against both donor MHC class I and II, whereas recipients of MHC class I-deficient grafts formed alloantibodies primarily against donor MHC class II Ag. These studies confirm that immune responses directed toward donor MHC class I alloantigens contribute to kidney transplant dysfunction in this model. Also, these findings suggest that, at least for renal transplants, genetic manipulations which reduce MHC class I expression may be effective in overcoming some of the effects of MHC incompatibility.

Animals↗
PubMed1993

Over the obstacles.

Although recognised as a good thing, day surgery still has barriers to overcome if it is to become a first-rate service, argue Caron Grainger and Rod Griffiths.

Ambulatory Surgical Procedures↗
PubMed1993

Cytotoxic actions and effects on intracellular Ca2+ and cGMP concentrations of sulphur-containing excitatory amino acids in cultured cerebral cortical neurons.

Effects of the sulphur-containing acidic amino acids (SAAs) cysteic acid (CA), homocysteic acid (HCA), cysteine sulphinic acid (CSA), homocysteine sulphinic acid (HCSA), and S-sulphocysteine (SC) on intracellular concentrations of Ca2+ ([Ca2+]i) and cGMP ([cGMP]i) as well as their cytotoxic actions were investigated in cultured cerebral cortical neurons. The glutamate receptor subtype selective antagonists APV (D-(-)-2-amino-5-phosphonopentanoate) acting on N-methyl-D-aspartate (NMDA) receptors and DNQX (6,7-dinitroquinoxaline-2,3-dione) acting on non-NMDA receptors were employed to obtain information about the involvement of glutamate receptor subtypes in these actions of the SAAs. It was found that all SAAs exerted a cytotoxic action on the neurons. The ED50 values for CSA, CA, HCSA, and HCA were around 30 to 50 microM and that for SC was about 150 microM. The glutamate transport blocker L-aspartate-beta-hydroxamate increased the efficacy of CSA and CA but had no effect on the cytotoxic actions of the remaining SAAs. In case of CA, HCA, and SC the cytotoxicity could be prevented by APV alone and for HCSA, DNQX could block the toxic action. DNQX reduced the toxicity of HCA somewhat but the presence of APV was required for complete protection. CSA toxicity could only be blocked by the combination of APV and DNQX. All SAAs induced an increase in [cGMP]i and [Ca2+]i and with regard to [Ca2+]i SC was the most potent and CA the least potent SAA. The effect of all SAAs on [cGMP]i could be blocked by APV alone whereas DNQX had no effect except in the case of HCSA where the response was blocked completely and HCA where the response was inhibited by 75%.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1993

A framework for quality assurance by professional organizations.

The Australian Diabetes Educators Association (ADEA) has undertaken policy development aimed at maintaining standards of practice and increasing professional skills. The components of a quality assurance framework have been identified and committees established to operationalize the objectives. Implementation of quality assurance projects has benefits for consumers and providers of health care. Knowledge and skills developed in the process of implementing quality assurance initiatives increase professional awareness and can be adapted to broaden practice parameters and create practice opportunities. This paper describes the approach to quality assurance developed by the committees and working parties of the ADEA that could be implemented in part or whole by professional groups seeking to ensure quality services by members.

Accreditation↗
PubMed1992

Neuronal and glial plasma membrane carrier-mediated uptake of L-homocysteate is not selectively blocked by beta-p-chlorophenylglutamate.

The proposed action of beta-p-chlorophenylglutamate (chlorpheg) as a selective blocker of L-homocysteate uptake was studied in primary cultures of mouse brain neurons and astrocytes and in rat brain synaptosomes. The preparations were incubated with 1 microM to 10 mM L-homocysteate and D-aspartate in the absence and presence of 7.5 mM chlorpheg. In each preparation uptake of the two amino acids comprised a saturable uptake and a non-saturable (passive diffusion) component. L-Homocysteate was of at least 100-fold lower affinity than D-aspartate as a substrate for the amino acid transporter. Chlorpheg was shown to be essentially equieffective as a weak competitive inhibitor of only the saturable uptake of L-homocysteate and D-aspartate. It is concluded that chlorpheg is not a selective blocker of L-homocysteate uptake.

Amino Acid Transport Systems↗
PubMed1992

Simultaneous measurement by HPLC of the excitatory amino acid transmitter candidates homocysteate and homocysteine sulphinate supports a predominant astrocytic localisation.

Primary cultures of mouse cerebral cortex neurons, cerebellar granule cells and cortical astrocytes were maintained in vitro for respectively 8-10, 7-10 and 21-24 days. Following these times, amino acids were extracted from the cells by use of ice-cold 70% (v/v) ethanol and the extracts lyophilised. The lyophilised extracts when resuspended were subjected to reverse-phase high performance liquid chromatographic (HPLC) analysis for detection of free amino acids. Samples of cell culture growth medium and water blanks were treated in a similar manner. Identification of L-homocysteate (HCA) and L-homocysteine sulphinate (HCSA) was undertaken by matching retention times with regard to external standards and by 'spiking' cell extracts with authentic compounds. On this basis, HCA and HCSA were consistently detectable in astrocytes at levels of, respectively, 72.3 +/- 33.7 pmol/mg protein (n = 24) and 49.4 +/- 28.7 pmol/mg protein (n = 24). However, in neurons, a peak corresponding to HCSA could not be detected above the background noise, while the area of the peak corresponding to HCA was always greater than, but not significantly different from, that of the background noise present in water blanks. HCA and HCSA were not detectable in the serum used for preparation of the cell culture growth medium. Taken together, these findings indicate a predominant localisation of HCA and HCSA in astrocytes which, at least in culture, appear to possess the metabolic machinery necessary for synthesising and storing these amino acids without any neuronal influence.

Amino Acids↗
PubMed1992

Synaptosomal plasma membrane transport of excitatory sulphur amino acid transmitter candidates: kinetic characterisation and analysis of carrier specificity.

The transport kinetics of the excitatory sulphur-containing amino acid (SAA) transmitter candidates, L-cysteine sulphinate (L-CSA), L-cysteate (L-CA), L-homocysteine sulphinate (L-HCSA), and L-homocysteate (L-HCA), together with their plasma membrane carrier specificity, was studied in cerebrocortical synaptosome fractions by a sensitive high performance liquid chromatographic assay. A high affinity uptake system could be demonstrated for L-CSA (Km = 57 +/- 6 microM; Vmax = 1.2 +/- 0.1 nmol/min/mg protein) and L-CA (Km = 23 +/- 3 microM; Vmax = 3.6 +/- 0.1 nmol/min/mg protein), whereas L-HCSA (Km = 502 +/- 152 microM; Vmax = 6.1 +/- 1.3 nmol/min/mg protein) and L-HCA (Km = 1550 +/- 169 microM; Vmax = 10.3 +/- 1.1 nmol/min/mg protein) exhibited much lower affinity as transport substrates. In all cases, only a single, saturable Na(+)-dependent component of uptake could be identified, co-existing with a non-saturable, Na(+)-independent influx component. Plasma membrane carrier specificity of the SAAs was established following comparison with other high-affinity neurotransmitter systems. High-affinity L-CSA and L-CA transport and low-affinity L-HCSA and L-HCA transport demonstrate strong positive correlations in inhibition profiles when compared against each other or individually against the high-affinity transport of L-[3H]glutamate, L-[3H]aspartate, or D-[3H]aspartate. Moreover, the transport systems for the excitatory SAAs exhibited a negative correlation when compared in inhibition profiles with the high affinity transport of both [3H] gamma-aminobutyric acid (GABA) and [3H]taurine.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1992

Homocysteine-induced alterations in extracellular amino acids in rat hippocampus.

The effects of DL-homocysteine, and DL-homocysteate, on extracellular levels of amino acids in the rat hippocampus have been studied using brain microdialysis. Hippocampal electroencephalogram activity was monitored simultaneously using an electrode attached to the dialysis probe. DL-Homocysteine (1200 mg/kg; i.p. injection) produced epileptic activity in hippocampus in an inconsistent manner. Alterations in electroencephalogram activity were not observed in urethane anaesthetized animals, whereas 50% of Hypnorm anaesthetized animals exhibited epileptic activity. DL-Homocysteate (2 mu mol; i.c.v.) induced epileptic activity in a majority of animals anaesthetized using urethane. Dialysate levels of aspartate were significantly elevated by homocysteine in both groups of animals. Conversely, dialysis levels of GABA were reduced. Dialysate levels of other amino acids measured (glutamate, glutamine, taurine, alanine and valine) were not affected significantly. Dialysate levels of taurine were increased significantly in animals injected with homocysteate. These data suggest that the imbalance in excitatory:inhibitory neurotransmission in the hippocampus caused by these alterations in extracellular levels of neuroexcitatory (i.e. aspartate) and neuroinhibitory (i.e. GABA) transmitters could underly the epileptic effect of homocysteine.

Amino Acids↗