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Biomedical subjects

C A Briggs

Publications and source records attributed to C A Briggs.

At least 37 records · Page 2Linked to original sources

Variations in the lumbosacral ligament and associated changes in the lumbosacral region resulting in compression of the fifth dorsal root ganglion and spinal nerve.

Sixty-five lumbosacral regions from adult cadavers were dissected and the position and relations of the lumbosacral ligament noted. The lumbosacral ligament was present in all specimens; in 22 (34%) it extended medially across the ventral ramus of the fifth lumbar nerve, and in six (9%) of these the underlying nerve was compressed and visibly flattened. On two of these specimens the nerve, together with its dorsal root ganglion, was removed, processed, and stained with Masson's trichrome. The compressed nerve showed increased thickness of endoneurial and perineurial connective tissue, and the cells of the dorsal root ganglion were smaller and surrounded by increased connective tissue, particularly at the periphery of the ganglion. Observation of the lumbosacral ligament and surrounding anatomical structures suggests that anatomical variation in this region may be attributed to the health of the lumbosacral articular elements. In those specimens showing compression of the fifth lumbar spinal nerve there was also narrowing of the lumbosacral interspace. In these the disc itself was compressed and showed degenerative changes. The articular processes at the lumbosacral joint were irregular, with thinning and fissuring of the artiuclar cartilage. It is suggested that the processes which lead to the further development of the ligament, by the formation of additional fibrous bands, are mechanical in nature and result from instability at the lumbosacral region itself. Instability subsequently leads to the initiation of a chain of degenerative changes, involving pathology at the lumbosacral disc and zygapophyseal joints.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Human alpha 7 nicotinic acetylcholine receptor responses to novel ligands.

Responses of the human alpha 7 nicotinic acetylcholine receptor (nAChR) in Xenopus laevis oocytes were quantified using two-electrode voltage clamp in the presence of barium (10 mM) to block secondary activation of Ca(2+)-dependent chloride currents. The effect of (S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT-418) and (2,4)-dimethoxybenzylidene anabaseine (GTS-21), two potential compounds for the treatment of Alzheimer's Disease, and of the natural product (+/-)epibatidine were compared to (-)nicotine. (+/-)Epibatidine acted as an agonist and was 64-fold more potent than (-) nicotine (EC50s = 1.30 +/- 0.11 microM and 83 +/- 10 microM, respectively). ABT-418 also was an agonist, 3-fold less potent and 75% as efficacious as (-)nicotine (EC50 = 264 +/- 34 microM). GTS-21, in contrast, inhibited the response to (-)nicotine at concentrations < or = 10 microM and itself elicited only a small response at higher concentrations (12% of the (-)nicotine response at 1 mM). Reversible blockade by methyllycaconitine (10 nM) corroborated the responses as due to activation of alpha 7 nAChR. This represents the first characterization of human alpha 7 nAChR responses to these novel nicotinic agonists.

Anti-Anxiety Agents↗

Informed refusal and patient autonomy: using reflection to examine how nursing knowledge and theory affect attitudes.

Reflection is a medium increasingly being used in nursing to explore critical incidents, promote learning and integrate theory and practice. In this paper reflection is used to explore the influences of different types of nursing knowledge and theory upon reactions to informed refusal of treatment and the concept of patient autonomy. The paper contains consideration of the care of a Jehovah's Witness and her family who refused a badly-needed blood transfusion.

Attitude of Health Personnel↗

Potential treatment of Alzheimer disease using cholinergic channel activators (ChCAs) with cognitive enhancement, anxiolytic-like, and cytoprotective properties.

Compounds that activate neuronal nicotinic acetylcholine receptors (nAChRs) may have potential benefit in the treatment of dementia, especially Alzheimer disease (AD). This article summarizes the preclinical pharmacology of ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole], a novel analog of (-)-nicotine that is being clinically evaluated for the treatment of AD. ABT-418 is a cholinergic channel activator (ChCA) with cognitive enhancement and anxiolytic-like activity possessing a substantially reduced side-effect profile compared to (-)-nicotine [Arneric SP, Sullivan JP, Briggs CA, et al. (S)-3-Methyl-5-(1-Methyl-2-Pyrrolidinyl)Isoxazole (ABT-418): A novel cholinergic ligand with cognition enhancing and anxiolytic activity. I. In vitro activity. J Pharmacol Exp Ther 1994 ;270:310-318; Decker MW, Brioni JD, Sullivan JP, et al. (S)-3-Methyl-5-( 1-Methyl-2-Pyrrolidinyl)Isoxazole (ABT-418): A novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther 1994a;270:319-328; Decker MW, Curzon P, B rioni JD, Arne ric SP. Effects of ABT-418, a novel cholinergic channel ligand, on place learning in septal-lesioned rats. Eur J Pharmacol 1994;261:217-222; Garvey DS, Wasicak JT, Decker MW, et al. Novel isoxazoles which interact with brain cholinergic channel receptors have intrinsic cognitive enhancing and anxiolytic activities. J Med Chem 1994;37:1055-1059]. ABT-418 may be the first agonist of nAChRs to be developed and evaluated specifically for the treatment of AD. Some brief speculation will be given on the potential benefits that this or other ChCAs may have in treating neurodegenerative disorders as compared with (-)-nicotine, and how this differs from other potential treatment approaches.

Alzheimer Disease↗

Cholinergic channel activators: novel opportunities for the treatment of CNS disorders.

Negative connotations associated with the use of (-)-nicotine has limited medicinal chemistry research in the area of nAChRs [5]. However, recent evidence suggests that a diversity of nAChR subunits exist, that each subtype may be involved in mediating specific neurochemical/behaviors, and that these subtypes have a defined pharmacology that may be selectively targeted [1]. (+/-)-Epibatidine, GTS-21 and ABT-418 differentially interact with nAChR subtypes to elicit a diversity of behavioral effects including analgesia, neuroprotection and cognitive enhancement. These agents therefore represent important new pharmacological probes to dissect the nAChR subtype(s) mediating specific pharmacological responses to nAChR activation.

Animals↗

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization.

A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been identified in mammalian brain using recombinant DNA technology. Alterations in the activity of these acetylcholinegated ion channels have been implicated in a number of central nervous system disorders including Alzheimer's disease (AD). The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by side effects that are the result of activation of both cholinergic and noncholinergic pathways in the central and peripheral nervous systems. This study sought to determine the in vitro selectivity of (S)-3-methyl-5-(1methyl-2-pyrrolidinyl)isoxazole (ABT 418), a novel analog of (-)-nicotine in which the pyridine ring was replaced with an isoxazole bioisotere, to activate nAChRs. ABT 418 was a potent inhibitor of [3H]-cytisine binding to nAChR in rat brain (Ki = 3 nM) but was inactive (Ki > 10,000 nM) in 37 other receptor/neurotransmitter-uptake/enzyme/transduction system binding assays, including those for alpha-bungarotoxin, muscarinic and 5-hydroxytryptamine3 receptors. In PC12 cells, patch-clamp studies indicated that ABT 418 was an agonist with an EC50 value of 209 microM, a potency to activate cholinergic channel currents some 4-fold less than that of (-)-nicotine (52 microM). Channel current responses elicited by ABT 418 were prevented by the cholinergic channel blocker, mecamylamine. ABT 418 was also approximately 10-fold less potent (EC50 value = 380 nM) than (-)-nicotine (40 nM) in increasing [3H]-dopamine release from rat striatal slices, an effect that was blocked by the nAChR antagonist, dihydro-beta-erythroidine (10 microM).2+ In contrast, ABT 418 appeared equipotent with (-)-nicotine in enhancing 86Rb+ flux from mouse thalamic synaptosomes. ABT 418 demonstrated an in vitro pharmacological profile of cholinergic channel activation that was robust at some nAChR, but not others. The reasons for this are unclear. However, a nAChR subtype selectivity may account for the in vitro potency differences of ABT 418 on various neurotransmitter systems, and the substantial separation between the cognitive enhancement/anxiolytic benefits, and the reduced central nervous system side-effect liabilities seen in vivo. ABT 418 represents the first neuronal nAChR ligand that differentiates the toxicities/liabilities and other negative aspects normally associated with liabilities and other negative aspects normally associated with (-)-nicotine from the potential pharmacological benefits of selective cholinergic channel activation.

Alkaloids↗

Evidence that nitric oxide mediates the cyclic GMP response to synaptic activity in the rat superior cervical ganglion.

Preganglionic nerve stimulation in the rat superior cervical ganglion (SCG) caused an increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) in a Ca(2+)-dependent manner. This increase was inhibited by oxyhaemoglobin, and blocked stereoselectively by an inhibitor of nitric oxide synthase, NG-nitro-L-arginine. Thus, nitric oxide or a similar substance appears to mediate the neuronal cyclic GMP response to synaptic activity in the rat SCG.

Animals↗

Potentiation of nicotinic transmission in the rat superior cervical sympathetic ganglion: effects of cyclic GMP and nitric oxide generators.

The efficacy of nicotinic transmission in the rat superior cervical ganglion in vitro (24-26 degrees C) was estimated by extracellular recording of the postganglionic compound action potential response to stimulation of the preganglionic nerve at a slow rate (one shock every 60 s). Atropine (2 microM) was included to block muscarinic transmission, and hexamethonium (200-250 microM) was used to produce a submaximal response sensitive to potentiation and inhibition of nicotinic transmission. Upon exposure to 1-100 microM 8-bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP), nicotinic transmission was potentiated by 6 +/- 1% (n = 4) to 89 +/- 5% (n = 5) in a dose-dependent manner. 8-Bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP, 10-100 microM) also potentiated nicotinic transmission (3.8 +/- 0.3% (n = 3) to 43 +/- 4% (n = 3)). However, 8-Br-cGMP was at least 2-fold more effective than 8-Br-cAMP. Sodium nitroprusside (0.1 microM to 1 mM) and sodium azide (0.1-100 microM) were used to stimulate the formation of endogenous cGMP52. Nicotinic transmission was potentiated by these substances also. The response was increased by 3.4 +/- 0.7% (n = 4) to 32 +/- 2% (n = 5) upon exposure to 0.1-100 microM sodium nitroprusside, and by 5.5 +/- 0.9% (n = 3) to 18 +/- 4% (n = 4) upon exposure to 0.1-100 microM sodium azide. Ferricyanide ion (10-100 microM) appeared to be ineffective, as would be expected if the effect of nitroprusside was due to the nitric oxide rather than the cyanide or ferric moieties.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

Multiple growth cartilages in the neural arch.

The origin of growth cartilages in the neural arch of human fetal vertebrae was investigated in an attempt to resolve the conflicting opinion on ossification in this region. Serial sections of developing vertebrae were examined, and three growth cartilages for each half of the neural arch were found. They have their origin from a single center of ossification. Endochondral bone formation similar to ossification in the diaphysis of a long bone occurs in the neural arch. This information may help in the understanding of how vertebral malformations such as scoliosis and spondylolysis occur during postnatal life.

Embryonic and Fetal Development↗

Microcomputer video image processing technology in working posture analysis: application to seated postures of keyboard operators.

A new two-dimensional video-based technique for the recording and analysis of working posture has been developed and applied to seated work. After initial set-up of the portable equipment in the workplace, and attachment of small adhesive retroreflective joint markers on the subject, an operator is not required for the remainder of the recording session. Analysis of the video recording is conducted in the laboratory using custom-written software and a commercially available image-processing package running on an IBM AT-compatible computer. After interactive set-up of a reference frame, the system is able to analyse the full video tape automatically, extracting video frames for analysis at approximately 30-s intervals. Poor image quality may occasionally necessitate interactive analysis. The system is capable of determining postural angles to an accuracy of 1-2 degrees , and thus represents a substantial improvement on other postural analysis systems which are able to be used readily in the workplace.

Journal Article↗

Factors related to working posture and its assessment among keyboard operators.

Video analysis of 15 keyboard operators was conducted over two four-hour periods to determine the effects of symptoms of over-use injury, the adjustability of the workstation, the type of keyboard, time of day and sex on working posture. The only factor which significantly affected posture was the type of keyboard, with operators at typewriters adopting a more extended shoulder position, reduced elbow flexion and increased wrist flexion, than those working at a VDU terminal. Analysis of the components of variance associated with repeated observations revealed that to minimise the variance associated with recording the posture of these subjects, and therefore obtain a representative mean posture, required at least nine observations for wrist angle, four for elbow angle, six for shoulder angle and three for trunk incline. The mean posture adopted by this group of operators was similar to the 'right angles' posture, with the trunk reclined 4 degrees , shoulder extended 1 degrees , elbow 92 degrees and wrist extended 7 degrees .

Journal Article↗

Activation of the 5-HT1C receptor expressed in Xenopus oocytes by the benzazepines SCH 23390 and SKF 38393.

1. A cloned 5-HT1C receptor expressed in Xenopus laevis oocytes was used to characterize the action of four dopamine D1-selective benzazepines at the 5-HT1C receptor. Additionally, the apparent binding of the D1-selective benzazepines to 5-HT1C receptors was measured in the choroid plexus of the pig. 2. In voltage-clamped oocytes expressing the cloned 5-HT1C receptor, 5-hydroxytryptamine (5-HT) elicited a characteristic inward current response with an EC50 of 13 nM. SCH 23390 acted as a stereoselective agonist (or partial agonist) with an EC50 of about 550 nM. SKF 38393 (1 microM-1 mM), SKF 77434 (100 microM), and SKF 82958 (100 microM) also acted as agonists (or partial agonists) at the cloned 5-HT1C receptor. SKF 38393 was not stereoselective at the 5-HT1C receptor. 3. The response to SCH 23390 activated slowly and, although the response contained many oscillations characteristic of the activation of the phosphatidylinositol signal transduction system, SCH 23390 rarely elicited the rapid spike-like response seen routinely in response to 5-HT. However, the responses to SKF 38393, SKF 77434, and SKF 82958 were identical in appearance to the response to 5-HT, except that the responses to the benzazepines were smaller. These comparisons were made by applying both a benzazepine and 5-HT to each individual oocyte expressing the cloned 5-HT1C receptor. 4. Consistent with the responses measured in oocytes, SCH 23390 bound stereoselectively to 5-HT1C receptors in the choroid plexus of the pig (Ki = 6.3 nM), and SKF 38393 bound non-stereoselectively with lower affinity (Ki = 2.0-2.2 microM).5. It is concluded that while these benzazepines demonstrate selectivity for the dopamine D1 receptor, they also can act as agonists or partial agonists at the 5-HT1c receptor in situ and as expressed in Xenopus oocytes. The oocyte expression system is useful for studies of the functional pharmacology of these 5-HTic receptors. Information about the pharmacological actions and variations in stereoselectivity among dopamine and 5-HT receptors should be of interest in modelling the interactions of ligands with these G-protein coupled receptors, and in the testing of such models through receptor mutagenesis.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Left superior vena cava with atrial displacement.

Two cadavers were dissected showing persistence of left-sided superior vena cava with atrial displacement and inversion of the venous drainage from the body wall (azygos system of veins). The presence of atrial displacement in relation to a persistent left superior vena cava observed in this study lends support to the view that haemodynamic factors influence the morphogenesis and development of the heart. The development of an asymmetrical venous pattern from a symmetrical venous drainage may be influenced by the same factors which influence the arterial end of the primitive heart tube.

Cadaver↗

Congenital diaphragmatic hernia through the oesophageal hiatus with nonrotation of the midgut. A case report.

Observations were made on the cadaver of an 86-year-old subject that presented with a congenital diaphragmatic hernia and nonrotation of the midgut. A hernial sac originating from the peritoneum near the oesophagogastric junction contained the midgut which had herniated through the oesophageal hiatus. An abnormally placed duodenum together with a variation in the drainage of the common hepatic duct were found. These findings are reviewed in relation to the development of the diaphragm and it is suggested that inadequate muscle differentiation in the primative mesenchyme contributes both to the occurrence of congenital oesophageal hiatus hernia and nonrotation of the midgut.

Aged↗

Effect of overuse injury and the importance of training on the use of adjustable workstations by keyboard operators.

The introduction of adjustable workstations for keyboard operators has been widely recommended to eradicate constrained working postures leading to the development of musculoskeletal disorders. A questionnaire evaluating the use of adjustable workstations was analyzed for 514 keyboard operators. Anthropometric dimensions and workstation settings were measured for 15 operators. There was no difference between sufferers and nonsufferers of overuse injury on the basis of adjustability of their equipment. However, sufferers were less satisfied with their equipment and there was evidence that inappropriate postures were being adopted. The availability of adjustable equipment per se does not necessarily solve the problem. The design of the equipment must be based on suitable anthropometric data and operators must be trained in the correct use of the equipment. The results of this study indicate a perceived need for training and/or information on workstation adjustment among operators, with a preference for information that is supplied verbally, rather than in literature form.

Anthropometry↗

Anthropometric dimensions and overuse injury among Australian keyboard operators.

This study was instigated to examine the relationship between overuse injury and anthropometric dimensions of Australian keyboard operators to investigate the possibility that a poor anthropometric fit of the workstation may result in greater incidence of such disorders. There were no differences between the anthropometric dimensions of sufferers and nonsufferers of overuse injury among the male keyboard operators. Among men in this study, stature and several other anthropometric dimensions as a proportion of stature were similar to those of North American and European populations for which equipment used in Australia is designed. In contrast, among women, significant differences were evident between sufferers and nonsufferers. The sufferers had greater hip widths and seat breadths, and a greater proportion were overweight (body mass greater than 26). There was also a tendency for shorter limb segment lengths among the sufferers. The women as a group, and the sufferers in particular, had several anthropometric dimensions that, as a proportion of stature, were outside the range of reference populations for design of Australian office workstations. The subject numbers in the present study are relatively small; however, they suggest that a proportion of the female population may not be accommodated by equipment currently in use. The increased proportion of sufferers who are overweight may suggest a relationship between overuse injury and lack of exercise, since the latter is well known to cause increased weight. A longitudinal study is needed to confirm this observation.

Adult↗

Ligaments of the lumbar spine: a review.

A thorough knowledge of the anatomy of the intervertebral ligaments is necessary to provide the basis for good clinical management of back injuries. This paper reviews the literature concerning the lumbar ligaments, including the zygoapophyseal joints. While general principles regarding the anatomy of the ligaments is relatively clear, areas of omission or discrepancy exist. There is very little substantiated information on: the dimensional characteristics of the ligaments; the fibre lengths of the facet capsule; the attachments of the anterior longitudinal ligament; the orientation of the interspinous ligament, and the extent of the supraspinous ligament.

Humans↗