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Biomedical subjects

H Muir

Publications and source records attributed to H Muir.

At least 19 recordsLinked to original sources
PubMed1998

The unanticipated difficult airway with recommendations for management.

PURPOSE: To review the current literature and generate recommendations on the role of newer technology in the management of the unanticipated difficult airway. METHODS: A literature search using key words and filters of English language and English abstracted publications from 1990-96 contained in the Medline, Current Contents and Biological Abstracts databases was carried out. The literature was reviewed and condensed and a series of evidence-based recommendations were evolved. CONCLUSIONS: The unanticipated difficult airway occurs with a low but consistent incidence in anaesthesia practice. Difficult direct laryngoscopy occurs in 1.5-8.5% of general anaesthetics and difficult intubation occurs with a similar incidence. Failed intubation occurs in 0.13-0.3% general anaesthetics. Current techniques for predicting difficulty with laryngoscopy and intubation are sensitive, non-specific and have a low positive predictive value. Assessment techniques which utilize multiple characteristics to derive a risk factor tend to be more accurate predictors. Devices such as the laryngeal mask, lighted stylet and rigid fibreoptic laryngoscopes, in the setting of unanticipated difficult airway, are effective in establishing a patient airway, may reduce morbidity and are occasionally lifesaving. Evidence supports their use in this setting as either alternatives to facemask and bag ventilation, when it is inadequate to support oxygenation, or to the direct laryngoscope, when tracheal intubation has failed. Specifically, the laryngeal mask and Combitube have proved to be effective in establishing and maintaining a patent airway in "cannot ventilate" situations. The lighted stylet and Bullard (rigid) fibreoptic scope are effective in many instances where the direct laryngoscope has failed to facilitate tracheal intubation. The data also support integration of these devices into strategies to manage difficult airway as the new standard of care. Training programmes should ensure graduate physicians are trained in the use of these alternatives. Continuing medical education courses should allow physicians in practice the opportunity to train with these alternative devices.

Education, Medical, Continuing↗
PubMed1998

Comparison of epidural anaesthesia with ropivacaine 0.5% and bupivacaine 0.5% for caesarean section.

PURPOSE: To compare ropivacaine 0.5% with bupivacaine 0.5% for epidural anaesthesia for Caesarean section. METHODS: Healthy pregnant women, scheduled for elective Caesarean section were enrolled into this randomized, double-blind, parallel-group study. Epidural block was obtained with 20-30 ml of ropivacaine (group R) or bupivacaine (group B) and surgery started when anaesthesia was reached T6. Maternal heart rate and blood pressure and fetal heart rate were assessed before the test dose and at five minute intervals until the end of surgery. At the same intervals, sensory and motor block characteristics were determined. Apgar scores and Neurologic and Adaptive Capacity Scores (NACS) were determined after delivery. Adverse events were recorded. RESULTS: Sixty-five patients were enrolled and data from 61 were available for analysis; 30 ropivacaine and 31 bupivacaine. Time from the end of the last injection to the start of surgery was 46 +/- 13 min (mean +/- SD) in gp R and 53 +/- 25 min in gp B (P:NS). The median duration of analgesia varied between 1.7 and 4.2 hr in gp R and between 1.8 and 4.4 hr in gp B (P:NS). In patients who developed Bromage 4 block, it persisted longer in those in gp B (2.5 hr) than in gp R (0.9 hr) (P < 0.05). The quality of analgesia was satisfactory in 27/29 patients (93%) in gp R and 27/31 patients (87%) in gp B (P:NS), although supplemental i.v. opioid was required in ten and seven patients, respectively. The most common adverse events in the mother were hypotension (63% gp R and 61% in gp B) (NS) and nausea (30% and 58%, in group R and B, respectively) (P = 0.05). Apgar scores were 7 after five minutes in all neonates. CONCLUSION: Ropivacaine 0.5% and bupivacaine 0.5% provided effective epidural anaesthesia for Caesarean section although supplementation with i.v. opioid was commonly required.

Adolescent↗
PubMed1997

Continuous epidural ropivacaine 0.2% for analgesia after lower abdominal surgery.

The purpose of this study was to determine whether a lumbar epidural infusion of ropivacaine 0.2% would provide effective analgesia with an acceptably low incidence of motor blockade and side effects after lower abdominal surgery. After combined general and epidural anesthesia and surgery, 125 patients were randomly assigned to receive either saline or ropivacaine 0.2% at a rate of 6, 8, 10, 12, or 14 mL/h (Groups R6, R8, R10, R12, and R14, respectively) for 21 h. Supplemental analgesia, if required, was provided with intravenous patient-controlled analgesia with morphine. Data were collected at 4, 8, and 21 h, and included morphine consumption, pain scores at rest and with coughing, motor and sensory block, and adverse events. Cumulative morphine consumption was less in Groups R10, R12, and R14 compared with the saline group. At 4 h analgesia was better among patients receiving ropivacaine, but at 21 h pain scores were identical. Sensory blockade at 8 and 21 h was greater in the ropivacaine groups compared with the saline group. Approximately 30% of R8, R10, and R12 patients, and 63% of R14 patients had demonstrable motor block of the lower limbs at 21 hours. We conclude that lumbar epidural ropivacaine 0.2% reduces parenteral morphine requirements but has little effect on pain scores and may be associated with motor blockade.

Abdomen↗
PubMed1996

Perioperative management of drug therapy, clinical considerations.

The objectives for the provision of a safe anaesthetic include rendering the patient analgesic for the procedure (amnesic if appropriate), with control of adverse haemodynamic perturbations, and muscle relaxation to facilitate surgery as necessary. This must be done with an understanding of the patient's pre-existing pathophysiology and drug therapy. This article focuses on the management of medications in the perioperative period from the practitioner's perspective. Areas of drug therapy examined include drugs affecting the cardiovascular, central nervous, haemostatic and endocrine systems. Review of the limited data available suggests that the safest course of action for the preoperative management of the vast majority of drug therapy is to continue such therapy until the time of surgery, particularly agents in which a withdrawal syndrome has been described, e.g. beta-adrenoceptor blocking agents, alpha 2-adrenoceptor agonists. Exceptions to this generalisation might include discontinuing ACE inhibitors prior to surgery as these agents may be associated with adverse haemodynamic changes during surgery. The management of drug therapy for patients receiving monoamine oxidase inhibitors (MAOIs) continues to be challenging due to the potential for drug interactions, e.g. severe hypertension with use of indirect-acting vasopressors and excitatory/depressive reactions with administration of pethidine (meperidine) or dextromethorphan. However, recent clinical experience has demonstrated the relative safety of continuing MAOIs prior to surgery by use of specific 'MAOI safe' anaesthetic techniques and/or substitution of short-acting MAOIs which do not irreversibly inhibit the enzyme. For drugs affecting the coagulation system, such as heparin and warfarin, prudence dictates discontinuing these agents whenever possible prior to surgery where it can be anticipated that haemorrhage will occur, e.g. vascular surgery, or where the consequences of even minor bleeding could be catastrophic, e.g. eye surgery. Controversy exists as to the management of patients receiving prophylactic low dose heparin for deep vein thrombosis prophylaxis or in whom intraoperative or postoperative anticoagulation is planned, e.g. aortic surgery, and in whom a regional anaesthetic technique is planned as part of the anaesthetic management. The data available suggest that, where prophylactic use of heparin is concerned, and provided the administration of the last dose of heparin and the institution of a regional anaesthetic nerve block does not occur at the same time, use of regional anaesthesia is not contraindicated in such circumstances. Where therapeutic anticoagulation is planned as part of the surgical management, there is a very small risk of the development of epidural or spinal haematoma when major central conduction nerve block is employed for anaesthesia, with resultant spinal cord compression and paralysis. These precautions do not apply to patients receiving aspirin or other nonsteroidal anti-inflammatory agents as there is a large clinical and published experience of the safety of regional anaesthesia in this group of patients. Patients treated with fibrinolytic agents are at increased risk for bleeding should surgery be required. For these patients, pre- and intraoperative use of agents with antifibrinolytic activity, e.g. aprotinin, has been demonstrated in case reports to be beneficial. Finally, recommendations for the management of patients who have received or are receiving glucocorticoids are given. Throughout the review, areas of uncertainty where further research is required are identified.

Animals↗
PubMed1995

The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules.

Chondrocytes are specialised cells which produce and maintain the extracellular matrix of cartilage, a tissue that is resilient and pliant. In vivo, it has to withstand very high compressive loads, and that is explicable in terms of the physico-chemical properties of cartilage-specific macromolecules and with the movement of water and ions within the matrix. The functions of the cartilage-specific collagens, aggrecan (a hydrophilic proteoglycan) and hyaluronan are discussed within this context. The structures of cartilage collagens and proteoglycans and their genes are known and a number of informative mutations have been identified. In particular, collagen fibrillogenesis is a complex process which can be altered by mutations whose effects fit what is known about collagen molecular structural functions. In other instances, mutations have indicated new functions for particular molecular domains. As cartilage provides the template for the developing skeleton, mutations in genes for cartilage-specific proteins often produce developmental abnormalities. The search for mutations amongst such genes in heritable disorders is being actively pursued by many groups, although mutation and phenotype are not always well correlated, probably because of compensatory mechanisms. The special nature of the chondrocyte is stressed in connection with its cell involvement in osteoarthritis, the most widespread disease of diarthrodial joints.

Animals↗
PubMed1992

Protein kinase C modulates parathyroid hormone- but not prostaglandin E2-mediated stimulation of cyclic AMP production via the inhibitory guanine nucleotide binding protein in UMR-106 osteosarcoma cells.

In UMR-106 osteosarcoma cells we found that PTH activated both the cAMP/protein kinase A and the Ca(2+)-dependent phosphoinositide/protein kinase C (PKC) pathways, but prostaglandin E2 (PGE2) activated only the cAMP pathway. Activation of PKC by the phorbol ester PMA had no effect on cAMP production but enhanced PTH-stimulated cAMP production by 50% or more; the effect on PGE2-induced cAMP was negligible. Inhibition of the alpha-subunit of the inhibitory guanine nucleotide binding protein (Gi) by pertussis toxin pretreatment also enhanced PTH-mediated cAMP production but had no effect on PGE2-induced cAMP production. These results suggest that although PTH-mediated adenylate cyclase activity is regulated via both the stimulatory (Gs) and inhibitory (Gi) guanine nucleotide binding proteins, only Gs regulates PGE2-mediated adenylate cyclase activity in UMR-106 cells. Costimulation with pertussis toxin and PMA did not increase PTH-stimulated cAMP production above that obtained with PMA alone. This implies a similar target of action for pertussis toxin and PMA, that is, the alpha-subunit of Gi. The alpha-subunit of Gi was found to be a substrate for in vitro PKC phosphorylation of membrane fractions from UMR-106 cells, seen as a +/- 40 kD band on SDS-PAGE. Stimulation of in situ 32P-labeled cells with either PMA or PTH also enhanced incorporation of 32P into the 40 kD band. Using the peptide antisera AS/7 and EC/2, we showed that pertussis toxin-labeled subunits of both Gi1 alpha/Gi2 alpha and Gi3 alpha could be immunoprecipitated, respectively, but immunoprecipitation of membrane proteins after in situ phosphorylation and stimulation with PMA precipitated only Gi2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗
PubMed1992

Increased release of matrix components from articular cartilage in experimental canine osteoarthritis.

The release rates of specific components of the proteoglycan aggregates (G1 domain, the chondroitin sulfate and keratan sulfate containing portion of the protein core, and link protein) of the articular cartilage of mature beagles were studied at early stages of canine experimental osteoarthritis (OA), generated by transection of the anterior cruciate ligament. Analysis of cartilage explants and synovial fluids indicates that at early stages of experimental OA, there is increased release of the proteoglycan aggregates of the articular cartilage. This involves a release from the tissue of the components of the proteoglycan that are specifically involved with aggregation together with the glycosaminoglycans of the proteoglycan. These components were detected at elevated levels in the media of explants of cartilage from the operated joint, and in the synovial fluids of the operated joints.

Animals↗
PubMed1992

Changes in proteoglycan turnover in experimental canine osteoarthritic cartilage.

The metabolism of newly-synthesised and total ("resident") proteoglycans was examined in control and osteoarthritic cartilage explants obtained from an experimental model (Pond and Nuki, 1973) of canine osteoarthritis. The following findings were obtained: (i) Non-labelled proteoglycans extracted from normal cartilage with 4 M guanidine HCl showed two bands visualised by staining with toluidine blue. The electrophoretic mobilities of proteoglycans from osteoarthritic cartilage were unchanged but the relative abundance of the slower migrating band increased with time after surgery. (ii) There were qualitative differences in the proteoglycan breakdown products released into the medium of explant cultures of osteoarthritic compared with control cartilage. This was apparent for both labelled and total unlabelled proteoglycans. (iii) There were similarities in the electrophoretic mobilities of the major labelled and non-labelled proteoglycan breakdown products suggesting that total ("resident") proteoglycans and newly-formed proteoglycans were degraded by similar mechanisms. There were however some differences in the labelled and non-labelled proteoglycans, suggesting that the mechanisms of breakdown were not identical. (iv) Immunoblotting techniques showed differences in the distribution of various glycosaminoglycans in proteoglycan breakdown products from control compared with osteoarthritic cartilage explant cultures. (v) Monoclonal antibodies 7-D-4 and 3-B-3 (which recognise unusual native chondroitin sulphate epitopes) showed greatly increased expression on proteoglycans from osteoarthritic cartilage compared with controls.

Animals↗
PubMed1990

Modulation of native chondroitin sulphate structure in tissue development and in disease.

Chondroitin sulphate proteoglycans are synthesised by different tissues and cell types, and the chondroitin sulphate chains are variably sulphated. Three monoclonal antibodies 3B3, 7D4 and 6C3 that recognise different native chondroitin sulphate epitopes have been used to investigate changes in structure during embryonic tissue development in the chick and in the response of mature canine articular cartilage during experimental osteoarthritis. Strong focal expression of the epitopes was seen during development of chick bursa, which was different for the three epitopes and which changed during 5 days of development. In embryonic chick limb, although chondroitin sulphate is present throughout the cartilage, the 3B3 epitope, which is at the non-reducing terminus of chains, was only expressed on chondroitin sulphate within one region of the sub-articular cartilage. In mature canine articular cartilage the expression of this epitope on proteoglycans was very low, but when determined 3 or 6 months after induction of experimental osteoarthritis the level was greatly increased in all joints tested (23/23). The abundance of the other two native chondroitin sulphate epitopes was also increased in this experimental disease. The results show that expression of the chondroitin sulphate epitopes detected by the monoclonal antibodies changes during cellular differentiation and development and suggests that it is closely controlled by the cells synthesising chondroitin sulphate chains.

Animals↗
PubMed1989

The influence of link protein stabilization on the viscometric properties of proteoglycan aggregate solutions.

The dynamic, steady-shear and transient shear flow properties of precisely prepared link-stable (s0 136, 66% aggregate) and link-free (s0 93, 59% aggregate) proteoglycan aggregate solutions at concentrations ranging from 10 to 50 mg/ml were determined using a cone-on-plate viscometer in a mechanical spectrometer. All proteoglycan solutions tested possessed: (1) linear viscoelastic properties - as measured by the dynamic complex modulus under small amplitude steady oscillatory conditions (1 less than or equal to omega less than or equal to 100 rad/s) - and (2) nonlinear shear-rate dependent apparent viscosities and primary normal stress difference under steady shearing conditions (0.25 less than or equal to gamma less than or equal to 250 s-1). Our transient flow data show that all proteoglycan aggregate solutions exhibited transient stress overshoot effects in shear stress and normal stress. From these steady and transient flow data, we conclude that link protein stabilized aggregates have significant effects on their dynamic and steady-shear properties as well as transient flow properties. The transient stress overshoot data provide a measure of the energy per unit volume of fluid required to overcome the proteoglycan networks in solution from a resting state. Thus we found that link-stable aggregates form much stronger networks than link-free aggregates. This is corroborated by the fact that link-stable aggregates form more elastic (lower than delta) and stiffer (higher [G*]) networks than link-free aggregates. The complete spectrum of viscometric flow data is entirely compatible with the proposed role of link protein in adding structural stability to the proteoglycan-hyaluronate bond. In cartilage, the enhanced strength of the networks formed by link-stable aggregates may play an important role in determining the material properties of the tissue and thereby contribute to the functional capacity of cartilage in diarthrodial joints.

Animals↗
PubMed1989

Adhesion of lymphoid cells to fibroblasts in tissue culture.

In this study we have examined the cellular and molecular specificity of lymphocyte interaction with fibroblasts. Using mitogen-activated T-cells, we found that attachment to fibroblasts was highly sensitive to protease treatment, and to an antibody raised against the purified lymphocyte plasma membrane, but it was not mediated by the MEL-14 surface antigen or phosphomannosyl receptors. Lymphocyte interaction with fibroblasts was also unaffected by monoclonal antibodies against the LFA-1, Mac-1, and Class II MHC antigen complexes. In contrast, adhesion of both T- and B-lymphocytes was strongly inhibited by fucoidan, a polymer of sulphated fucose, whereas fucose, mannan, and mannose 6-phosphate had no effect. Both B- and T-lymphoid cell lines were able to recognise and adhere to fibroblasts, although the marked differences between the attachment of the different types of cell did not appear to be related to their immunological function. The attachment of most of the cell lines was prevented by the presence of fucoidan, whereas the inhibition of binding of each of the lymphoid lines in the presence of the anti-T-lymphocyte plasma membrane antibody varied widely. These findings suggest that lymphocyte attachment to fibroblasts involves multiple cell surface receptors, and that these are expressed at different levels on specific T- and B-cells.

Animals↗
PubMed1989

Fibroblast matrix and surface components that mediate cell-to-cell interaction with lymphocytes.

The interaction between lymphocytes and fibroblasts in vitro has been examined using a quantitative ELISA assay to measure the binding of T and B cells to monolayer cultures of human dermal fibroblasts. This was carried out on microtiter culture plates, using an anti-Thy-1 monoclonal antibody, to determine the attachment of murine T lymphocytes and an affinity-purified polyclonal anti-IgM antibody to measure B cell binding. Both types of lymphocyte were found to adhere strongly to intact human fibroblasts, and also had high levels of attachment to purified fibroblast plasma membranes and extracts of the fibroblast extracellular matrix. Attachment, particularly of B lymphocytes, also took place onto plastic surfaces coated with fibronectin, but not to collagens or to intact fibroblasts that had been fixed with a low concentration of paraformaldehyde. Lymphocyte binding to fibroblasts was partially prevented by a monoclonal antibody against fibroblast MHC class II antigens, but not against the class I membrane complex, or by polyclonal antiserum to the cell surface mannose 6-phosphate receptor. In addition, although both lymphocyte types were able to adhere to fibro-nectin, the presence of antibody against fibronectin or the synthetic peptide Arg-Gly-Asp-Ser, had no effect on their attachment to fibroblasts. Thus, lymphocyte adhesion may occur by fibronectin, but other types of interactions with fibroblasts also appear to take place.

Animals↗
PubMed1988

Dermatan sulphate proteoglycan from human articular cartilage. Variation in its content with age and its structural comparison with a small chondroitin sulphate proteoglycan from pig laryngeal cartilage.

Low molecular mass proteoglycans (PG) were isolated from human articular cartilage and from pig laryngeal cartilage, which contained protein cores of similar size (Mr 40-44 kDa). However, the PG from human articular cartilage contained dermatan sulphate (DS) chains (50% chondroitinase AC resistant), whereas chains from pig laryngeal PG were longer and contained only chondroitin sulphate (CS). Disaccharide analysis after chondroitinase ABC digestion showed that the human DS-PG contained more 6-sulphated residues (34%) than the pig CS-PG (6%) and both contained fewer 6-sulphated residues than the corresponding high Mr aggregating CS-PGs from these tissues (86% and 20% from human and pig respectively). Cross-reaction of both proteoglycans with antibodies to bovine bone and skin DS-PG-II and human fibroblasts DS-PG suggested that the isolated proteoglycans were the humans DS-PG-II and pigs CS-PG-II homologues of the cloned and sequenced bovine proteoglycan. Polyclonal antibodies raised against the pig CS-PG-II were shown to cross-react with human DS-PG-II. SDS/polyacrylamide-gel analysis and immunoblotting of pig and human cartilage extracts showed that some free core protein was present in the tissues in addition to the intact proteoglycan. The antibodies were used in a competitive radioimmunoassay to determine the content of this low Mr proteoglycan in human cartilage extracts. Analysis of samples from 5-80 year-old humans showed highest content (approximately 4 mg/g wet wt.) in those from 15-25 year-olds and lower content (approximately 1 mg/g wet wt.) in older tissue (greater than 55 years). These changes in content may be related to the deposition and maintenance of the collagen fibre network with which this class of small proteoglycan has been shown to interact.

Age Factors↗
PubMed1988

Cell contact induces the synthesis of a lysosomal enzyme precursor in lymphocytes and its direct transfer to fibroblasts.

The activity of a lysosomal enzyme, alpha-D-mannosidase (EC 3.2.1.24), increased markedly in normal lymphocytes when they were cultured together with fibroblasts from a patient with an inherited deficiency of this enzyme. Cell-to-cell contact was obligatory for this increase in activity, which also required new protein synthesis. The enzyme induced in the co-cultured lymphocytes was a high molecular weight form of alpha-D-mannosidase that was not detected in lymphocytes cultured alone, which had only the low molecular weight mature enzyme. It was this precursor form alone that was directly transferred to the mannosidosis fibroblasts, where it was present initially in organelles of low density. When the culture period was extended the lymphocyte precursor enzyme was transported to the heavy lysosomes in the recipient cells, and correctly processed to the functionally effective mature enzyme.

Animals↗
PubMed1988

Hyaluronic acid in human articular cartilage. Age-related changes in content and size.

Total tissue content and molecular mass of hyaluronic acid was determined in papain digests of human articular cartilage using a sensitive radiosorbent assay [Laurent & Tengblad (1980) Anal. Biochem. 109, 386-394]. 1) Hyaluronic acid content increased from 0.5 microgram/mg wet wt. to 2.5 micrograms/mg wet wt. between the ages of 2.5 years and 86 years. 2) Hyaluronic acid chain size decreased from Mr 2.0 x 10(6) to 3.0 x 10(5) over the same age range. 3) There was no age-related change in the size of newly-synthesized hyaluronic acid, which was of very high molecular mass, in both immature and mature cartilage. The results are consistent with an age-related decrease in proteoglycan aggregate size and suggest that modification of the hyaluronic acid chain may take place in the extracellular matrix.

Adolescent↗
PubMed1988

Lymphocytes transfer only the lysosomal form of alpha-D-mannosidase during cell-to-cell contact.

We have examined the changes in the activities of the different types of alpha-D-mannosidase when fibroblasts from patients deficient in the lysosomal form of the enzyme are cultured together with normal lymphocytes. Our results show that whereas the mannosidosis cells acquired high levels of this enzyme, the activities of both the Golgi and the endoplasmic reticulum forms of alpha-D-mannosidase remained the same as in the fibroblasts cultured alone in the absence of lymphocytes. The increase in the activity of the lysosomal enzyme in the cocultured fibroblasts was not affected by the presence of mannose 6-phosphate or alpha-methyl mannoside, inhibitors of receptor- and lectin-mediated uptake of lysosomal enzymes, respectively, but it did require cell-to-cell contact. Ion-exchange HPLC and electrophoresis in polyacrylamide gradient gels showed that the acquired enzyme had the same elution profile and molecular size as the lysosomal form of the enzyme present in the lymphocytes. Immunoprecipitation studies using antibody specific for the lymphocyte type of lysosomal alpha-D-mannosidase confirmed that the increased activity in the cocultured mannosidosis cells resulted from the acquisition of the lymphocyte enzyme. Cytochemical examination revealed, however, that the transferred lymphocyte enzyme was localized in cytoplasmic organelles in the peripheral regions of the recipient fibroblasts. These results show that lymphocytes transfer only the lysosomal form of alpha-D-mannosidase during cell-to-cell contact with mannosidosis cells.

Animals↗