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Biomedical subjects

M G Gillan

Publications and source records attributed to M G Gillan.

At least 19 recordsLinked to original sources
PubMed2001

Influence of imaging on clinical decision making in the treatment of lower back pain.

PURPOSE: To assess the impact of cross-sectional imaging with magnetic resonance (MR) imaging or computed tomography (CT) on clinical decision making for patients with lower back pain (LBP). MATERIALS AND METHODS: A randomized controlled before-and-after study was performed in 145 patients who had symptomatic lumbar spinal disorders and had been referred to orthopedists or neurosurgeons. Participants were a subgroup within a multicenter pragmatic randomized comparison of two imaging policies on LBP treatment: "imaging" versus "no imaging," unless a clear indication developed. Paired assessments were made of diagnosis, diagnostic confidence, proposed treatment, treatment confidence at trial entry and follow-up, and expectations of imaging. Data were analyzed according to the groups as randomized. RESULTS: At follow-up, there were no statistically significant differences between the groups with respect to diagnosis or treatment plans. Significant increases in diagnostic and therapeutic confidence between trial entry and follow-up were observed for both groups, with a significantly greater increase in diagnostic confidence (P =.01) in the imaging group. CONCLUSION: Imaging may increase diagnostic confidence but has minimal influence on diagnostic or therapeutic decisions for patients with LBP. The results highlight the need for evidence-based guidelines for imaging in LBP treatment.

Adult↗
PubMed2000

Recruitment to multicentre trials: the impact of external influences.

A multicentre randomised controlled trial needs to recruit sufficiently large numbers of centres, clinicians and patients Delays in reaching recruitment targets are common and often necessitate extended recruitment periods with associated increased costs. The Scottish Back Trial and the MRC Laparoscopic Hernia Trial are used to illustrate how national clinical, economic and political factors can impact on the conduct of a multicentre trial. Changes in clinical practice, restructuring of the NHS and research and development funding, and changes in the procedures for obtaining local research ethics committee approval had adverse effects on recruitment. In addition, the extent to which changes in patient knowledge and attitudes to clinical trials could influence recruitment should not be ignored. In response to these obstacles both trials extended the recruitment period, identified additional recruitment centres and reduced the overall sample size. External factors which could compromise the successful completion of a d trial need to be recognised and addressed at an early stage.

Herniorrhaphy↗
PubMed1998

The natural history of trunk list, its associated disability and the influence of McKenzie management.

Lumbosacral list is a clinical sign that is frequently associated with low back pain and intervertebral disc lesions. This study examines the influence of McKenzie management on the natural history of trunk list. Patients with trunk list and low back pain were randomised into two groups: a control group receiving non-specific back massage and general back care advice, and a group treated according to the McKenzie protocol. Trunk list was measured over a period of 90 days and patients completed Oswestry Disability Questionnaires. There was a significantly greater resolution of list after 90 days in the group receiving McKenzie treatment compared to the control group. There was poor correlation between list magnitude and Oswestry scores. These data support previous observations that trunk list is not necessarily related to the degree of physical disability. The McKenzie method of assessment and treatment may assist in the resolution of trunk list, but it was ineffective in improving clinical condition.

Adult↗
PubMed1996

A comparison of methods for measuring trunk list. A simple plumbline is the best.

STUDY DESIGN: Trunk list was measured using three different techniques to compare accuracy, precision, and ease of use. OBJECTIVE: To obtain a reproducible technique for further studies of the nature, cause, and clinical relevance of trunk list. SUMMARY OF BACKGROUND DATA: Gravity-induced trunk list is a clinical sign that is frequently observed in patients with low back pain and has been associated with intervertebral disc lesions. METHODS: Patients with trunk list participated in a comparison of three techniques to determine list magnitude and direction. Paired measurements of trunk list were obtained from each patient using three techniques: a plumbline, a projected shadow, and the 3SPACE Isotrak (McDonnell Douglas Electronics Company, Colchester, VT). In addition, intra- and interobserver reliability of list measurement was assessed by comparison of paired measurements by each of two observers. RESULTS: List measurements assessed by the plumbline and the projected shadow techniques were not significantly different, but the Isotrak produced data that differed significantly (P < 0.05) from both of these techniques. Comparison of intra- and interobserver repeatability of list measurement using the plumbline technique indicated no significant difference between repeated measures by each observer or between two observers. CONCLUSIONS: A plumbline is the most useful instrument for measuring static trunk list, but its limitations and the need for standardization of measurement technique must be recognized.

Adult↗
PubMed1991

Electrically-induced release of opioid peptides from the guinea-pig myenteric plexus preparation.

Preparations of guinea-pig myenteric plexus-longitudinal muscle suspended in Krebs solution were stimulated electrically in the presence of cycloheximide and tetraethylammonium. The amounts of eleven endogenous opioid peptides released into the perifusing Krebs solution were determined and correlated with the decrease in the tissue contents induced by stimulation. For pro-enkephalin fragments the ratio of release to reduction in tissue contents was 29 to 43% for [Met]enkephalin, [Leu]enkephalin, [Met]enkephalyl-RF and [Met]enkephalyl-RGL. With [Met]enkephalyl-RRV-NH2 (BAM-8) the ratio was higher by 50% or more. However, it is of interest that there was no release of the probable precursor [Met]enkephalyl-RRVGRPEWWMDYQ(BAM-18). In this context it may be important that BAM-8 is the only endogenous opioid peptide having -NH2 at the C-terminal. The low tissue levels of pro-dynorphin derived peptide have made estimation of release unreliable.

Amino Acid Sequence↗
PubMed1985

Species differences in the concentrations and distributions of opioid binding sites.

Binding at the mu, delta- and kappa-types of opioid binding sites was compared in homogenates from the brains of guinea-pig, rabbit, rat and two mouse strains, under conditions of selective labelling. Species differences were shown by two observations. Firstly, analysis of saturation curves in homogenates of brain from which the cerebellum had been removed showed that in guinea-pig brain the opioid binding sites consist of 24% mu-sites, 32% delta-sites and 44% kappa-sites. In contrast, in rabbit brain the corresponding values are 43% mu-sites, 19% delta-sites and 37% kappa-sites and in rat brain, 46% mu-sites, 42% delta-sites and 12% kappa-sites. In the brains of DBA/2 mice the opioid binding sites are comprised of 51% mu-sites, 29% delta-sites and 20% kappa-sites and in C57BL/10 mice, of 44% mu-sites, 35% delta-sites and 21% kappa-sites; these strain differences are due to significant differences in the concentrations of the mu-sites. Secondly, species differences were found when the binding of single concentrations of tritiated ligands (1 X KD value in whole brain) was determined at mu-, delta- and kappa-sites in six brain regions from guinea-pig, rat or rabbit.

Animals↗
PubMed1985

[3H]-Dynorphin A (1-8): degradation profile and binding characteristics in brain homogenates.

[3H]-Dynorphin A (1-8) was degraded in brain homogenates at 25 degrees and even at 0 degree C. The peptidase inhibitors bestatin and captopril almost completely protected[3H]-dynorphin A (1-8) from degradation at 0 degree C but had only little effect on binding at this temperature. At 25 degrees C, the binding of [3H]-dynorphin A (1-8) was markedly improved by addition of bestatin, captopril and L-leucyl-L-arginine, which afforded some, but not complete protection from degradation. The results of saturation binding assays at 25 degrees C in the presence of the peptidase inhibitors were variable. However, it was found from saturation binding assays at 0 degree C that the maximum binding capacity for [3H]-dynorphin A (1-8) at the kappa-site is similar to that of [3H]-(-)-bremazocine and [3H]-dynorphin A (1-9).

Animals↗
PubMed1985

Kappa-binding and degradation of [3H]dynorphin A (1-8) and [3H]dynorphin A (1-9) in suspensions of guinea pig brain membranes.

Following incubation of [3H]dynorphin A (1-8) and [3H]dynorphin A (1-9) with suspensions of guinea pig brain membranes, analysis of the supernatants by HPLC has shown that both peptides are degraded at 25 degrees C and at 0 degrees C. Bestatin and captopril reduce degradation at 0 degrees C but for a similar degree of protection at 25 degrees C arginine-containing dipeptides are also required. The effects of these peptidase inhibitors on the degradation profiles indicate that [3H]dynorphin A (1-8) has three main sites of cleavage: the Tyr1-Gly2, Arg6-Arg7, and Leu5-Arg6 bonds. With [3H]dynorphin A (1-9) as substrate the Arg7-Ile8 and Ile8-Arg9 bonds are also liable to cleavage. In binding assays, in contrast to the effects of peptidase inhibitors on the degradation of unbound [3H]dynorphin A (1-8) and [3H]dynorphin A (1-9), bestatin and captopril have little effect on the binding characteristics of the tritiated dynorphin A fragments at the kappa-site at 0 degrees C. However, at 25 degrees C binding is low in the absence of peptidase inhibitors. When binding at mu- and delta-sites is prevented, the maximal binding capacities of [3H]dynorphin A (1-8), [3H]dynorphin A (1-9), and [3H](-)-bremazocine at the kappa-site are similar; [3H]dynorphin A (1-9) has 5-10 times higher affinity for the kappa-site than [3H]dynorphin A (1-8). Comparison of the effects of peptidase inhibitors on unbound dynorphin A fragments with their effects in binding assays suggests that the bound peptides are protected from the action of peptidases.

Animals↗
PubMed1984

Selectivities of opioid peptide analogues as agonists and antagonists at the delta-receptor.

The endogenous opioid ligands interact with more than one of the mu-, delta- and kappa-binding sites. By the use of binding assays and bioassays, enkephalin analogues have been assessed for their selectivity for binding at the delta-binding site and for their agonist and antagonist activities at the delta-receptor. The electrically-induced contractions of myenteric plexus-longitudinal muscle preparations of the guinea-pig ileum were inhibited by mu- and kappa-receptor ligands. Inhibitions were seen with mu-, delta- and kappa-receptor ligands in the mouse vas deferens, mainly with mu-receptor ligands in the rat vas deferens and only with kappa-receptor ligands in the rabbit vas deferens. From observations on a considerable number of [Leu5] enkephalin analogues, it has been concluded that [D-Pen2, D-Pen5] enkephalin and [D-Pen2, L-Pen5] enkephalin are the most selective delta-agonists and that N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH is the most selective antagonist (Aib = alpha-aminoisobutyric acid). The binding of these peptides at the delta-site is 99% of the total binding. As to potency, the agonists are superior to the antagonists.

Animals↗
PubMed1984

Radioligands for probing opioid receptors.

The three endogenous opioid precursors of almost 30000 Da are pro-opiocortin, proenkephalin and prodynorphin. Pro-opiocortin contains beta-endorphin, melanotropins and ACTH. Proenkephalin yields one [Leu5]enkephalin, three [Met5]enkephalins, one [Met5] enkephalyl-Arg-Arg-Val-NH2 (metorphamide or adrenorphin), one [Met5]enkephalyl-Arg-Gly-Leu and one [Met5]enkephalyl-Arg-Phe. [Leu5]enkephalin is common to all fragments of prodynorphin; its carboxyl extension by Arg-Lys leads to alpha- and beta-neo-endorphin and its carboxyl extension by Arg-Arg gives two dynorphins A and B of 17 and 13 amino acids, respectively. Another endogenous peptide is dynorphin A (1-8). The three main opioid binding sites are mu, delta and kappa. Their analysis has been facilitated by the synthesis of analogues of peptides and non-peptide compounds, which have selective agonist or antagonist action at only one site. The various physiological roles of the three types of the opiate receptor have so far not been sufficiently investigated.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1983

[3H]-dynorphin A (1-9): binding characteristics and degradation profile in brain homogenates.

[3H]-Dynorphin A (1-9) is rapidly degraded in brain homogenates, even at 0 degree C. Although protection from degradation at O degree C, and to a lesser extent at 25 degrees C, was obtained with a combination of bestatin, L-leucyl-L-leucine, L-arginyl-L-arginine and captopril, these peptidase inhibitors had little effect on binding at 0 degree C. At the kappa-site, the maximum binding capacity of [3H]-dynorphin A (1-9) at 0 degree C was similar to that at 25 degrees C but it is suggested that, even after suppression of mu- and delta-binding, [3H]-dynorphin A (1-9) may bind to more than one site for which it has differing affinities at 0 degree C.

Animals↗
PubMed1982

Interaction of p-nitrophenylalanine enkephalins with mu-, delta- and kappa-subtypes of the opiate receptor.

Substitution of L-p-nitrophenylalanine for phenylalanine in position 4 of [D-Ala2, KLeu-NH2(5)]enkephalin analogues increased their affinity for mu-, delta- and kappa-binding sites in guinea-pig brain, increased their potency to inhibit electrically evoked contractions of the guinea-pig ileum and mouse vas deferens, and increased their analgesic potency in the mouse tail flick test, Introduction of L-adamantylalanine, but not of L-neopentylglycine, in position 5 resulted in a loss of activity.

Animals↗
PubMed1982

Spectrum of the mu, delta- and kappa-binding sites in homogenates of rat brain.

1 In homogenates of rat brain, the binding characteristics of tritiated opiates and opioid peptides were examined and the relative capacities of mu-, delta- and kappa-binding sites of the opiate receptor determined by saturation analysis.2 In competition experiments, binding of the selective mu-ligand [(3)H]-[D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin at the mu-site was displaced by [D-Ala(2),D-Leu(5)]enkephalin with rather low affinity (K(I) = 12.6 nM) and more readily by the ketazocine-like compounds (-)-ethylketazocine (K(I) = 3.1 nM) and (-)-bremazocine (K(I) = 0.32 nM), which also displaced the binding of [(3)H]-[D-Ala(2),D-Leu(5)]enkephalin from the delta-site. In contrast, the binding to the kappa-site was easily displaced by ethylketazocine (1.0 nM) and bremazocine (0.37 nM) but not by the mu-ligand [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (K(I) = 2000-3000 nM) or the delta-ligand [D-Ala(2),D-Leu(5)]enkephalin (K(I) > 20,000 nM).3 The dissociation equilibrium constant (K(D)) and the binding capacity (pmol/g) of the mu-binding site were determined with the selective mu-ligand [(3)H]-[D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin. For the delta-site, [(3)H]-[D-Ala(2),D-Leu(5)]enkephalin was used in the presence of unlabelled [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin in order to suppress cross-reactivity to the mu-binding site. For the estimation of kappa-binding, [(3)H]-(+/-)-ethylketazocine or [(3)H]-(-)-bremazocine were used in the presence of unlabelled mu- and delta-ligands for the suppression of cross-reactivities to the mu- and delta-binding sites.4 In rat brain the capacity of the mu-binding site was 7.3 pmol/g brain, that of the delta-binding site 6.7 pmol/g brain and that of the kappa-binding site 2.0 pmol/g brain. Thus, the kappa-binding site had the lowest value whereas in the guinea-pig brain the capacity of the mu-binding site was lower than that of the delta- or kappa-binding site.

Animals↗
PubMed1981

Tobacco mosaic virus-enkephalin conjugates: potentiation of opioid activity.

Covalent tobacco mosaic virus-enkephalin analogue conjugates containing between 5 and 450 agonist molecules attached through their C-terminal amino acids were prepared and assayed in pharmacological and binding assays that distinguish between mu- and delta-receptors. Increases in peptide- and receptor-specific potency and affinity were observed with a certain preference of mu- over delta-receptors. The results may become important for mapping receptors or for isolating opiate receptor-bearing membrane vesicles.

Animals↗
PubMed1981

Some 14 beta-substituted analogues of N-(cyclopropylmethyl)normorphine.

A series of N-(cyclopropylmethyl)-14 beta-substituted-normorphine analogues was synthesized and tested for opioid agonist and antagonist activity in the guinea pig ileum and mouse vas deferens preparations. The 14 beta-bromo compound proved to be a pure antagonist equal in potency to naloxone in the guinea pig ileum assay. In contrast to N-(cyclopropylmethyl)-14 beta-hydroxynormorphine which was a pure antagonist, the corresponding sulfur analogue was about equal to nalorphine in agonist and antagonist potency.

Animals↗