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Biomedical subjects

G Carroll

Publications and source records attributed to G Carroll.

At least 37 records · Page 2Linked to original sources

Oncostatin M (OSM) stimulates resorption and inhibits synthesis of proteoglycan in porcine articular cartilage explants.

Oncostatin M (OSM) is structurally and functionally similar to leukaemia inhibitory factor (LIF), interleukin 6 (IL-6), interleukin 11 (IL-11) and ciliary neurotrophic factor (CNTF). We have previously shown that LIF stimulates proteoglycan release and suppresses proteoglycan synthesis in pig and goat cartilage explants. The aim of this study was to determine whether OSM and related cytokines influence proteoglycan metabolism in pig cartilage explants. Slices of pig articular cartilage were incubated for 6 days in serum free DMEM with or without cytokines. The total proteoglycan content in papain digested cartilage explants and medium was determined by the 1,9 dimethylmethylene blue method. Cytokine activity was assessed by determining the percentage release of total proteoglycan. To evaluate proteoglycan synthesis, cartilage was cultured for 48 h under the same conditions and in the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose dependent stimulation of proteoglycan release and suppression of proteoglycan synthesis were observed with rhOSM. IL-6, IL-11 and CNTF also inhibited proteoglycan synthesis in a dose dependent manner but the degree of inhibition was less than that for OSM and these cytokines had no significant effect on proteoglycan release. New biological effects have been identified for OSM and the related cytokines CNTF and IL-11. All three of these cytokines, like LIF and IL-6, suppress proteoglycan synthesis in pig cartilage explants. This common effect suggests that the gp130 subunit of the receptors for these cytokines may represent a common signalling pathway whereby proteoglycan synthesis is regulated. Whilst OSM and LIF stimulate proteoglycan catabolism; IL-6 IL-11 and OSM do not. Thus these effects are not always coupled and activation of gp130 alone may not be a sufficient signal for proteoglycan catabolism.

Animals↗

Accuracy of a portable interpretive ECG machine in diagnosis of acute evolving myocardial infarction.

From a study of 526 patients having automatic ECG analysis, criteria were established which diagnosed acute evolving Q wave myocardial infarction with 71% sensitivity and 98% specificity. Specificity was 100% when patients with known previous Q wave infarction were excluded. In pre-hospital practice the high sensitivity and specificity were maintained. This method appears appropriate, when other criteria are met, for paramedic-initiated pre-hospital thrombolysis with remote supervision of a cardiologist by telephone.

Adult↗

Analysis of the genes involved in the insulin transmembrane mitogenic signal in Chinese hamster ovary cells, CHO-K1, utilizing insulin-independent mutants.

CHO-K1 cells, wild type (WT), grow in a defined medium with insulin as the only essential hormone. When starved for insulin, these cells accumulate in G0/G1 stage. Insulin binding to its receptor stimulates DNA synthesis and cell division and induces an increase in abundance of mRNA for c-fos, c-jun, Krox-20, Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE. The kinetics of induction of these genes are similar to that shown with serum induction of 3T3. These genes show maximum stimulation at insulin concentrations of 20, 160, or 320 ng/ml and their expression is inhibited at higher concentrations. The addition of cycloheximide results in superinduction. The WT and insulin-independent mutants show no detectable signal for KC, fos-b, or nur77 and no increase over the basal level of pI-15, probably eliminating these genes as participants in the insulin mitogenic signal. These mutants synthesize DNA in the absence of insulin at rates that vary from 4 to 12 times that of the quiescent (insulin unstimulated) WT and are further inducible by insulin. The mutants have "constitutive" levels of Krox-24 (zif/268), fra-1, jun-B, c-myc, and JE (INS-type 2 genes) mRNAs that vary from mutant to mutant, reaching a maximum of an 8-fold increase for fra-1 and JE over the quiescent WT levels. There were no detectable levels of mRNA for genes c-fos and Krox-20 and no increase in level of mRNA for c-jun (INS-type 1 genes) as compared to the quiescent WT. Thus, although these INS-type 1 and type 2 genes may be involved in the full insulin mitogenic signal, the constitutive up-regulation of only genes in INS-type 2 is sufficient for insulin-independent DNA synthesis and cell division. Analysis of hybrids constructed between WT and mutant 27 indicate that the mutant phenotype is recessive, pointing to the existence of a regulatory gene producing a negative regulator.

Animals↗

Comparison of keratan sulphate concentrations and the size distribution of proteoglycans in the synovial fluid of patients with osteoarthritis and pyrophosphate arthropathy.

In order to evaluate the effect of calcium pyrophosphate dihydrate (CPPD) deposition on articular cartilage catabolism, the proteoglycans released into normal synovial fluid were compared with those in synovial fluid obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPA) and acute pyrophosphate arthropathy (APA). Keratan sulphate (KS) was measured by the modified 1,9-dimethylmethylene blue (DMB) assay in synovial fluids treated with chondroitin ABC lyase. This enzyme was found to eliminate all of the sulphated glycosaminoglycans in synovial fluid except KS. In OA, CPA and APA the concentrations of KS were found to be significantly higher than in normal synovial fluid (NSF) (P less than 0.01). Similar KS concentrations were observed in CPA and APA. In CPA they were significantly higher than in OA (P less than 0.02). The size distribution of proteoglycan fragments varied between different patients with the same disease, but only minor differences were observed in patients with OA and CPA who were matched for age, sex and disease severity. Furthermore, the size distribution of proteoglycan fragments in the acute and chronic phases of pyrophosphate arthritis was similar. Thus although in pyrophosphate arthritis the rate at which proteoglycans are released from the cartilage may be greater than in OA or normal joints, the fundamental processes governing the release of these macromolecules may be the same.

Adult↗

Preventive strategies in management of acute myocardial infarction.

Recent studies on pathogenetic mechanisms, supplemented by findings in clinical trials point the way to a logical approach to acute evolving myocardial infarction. This is designed in the earliest stage to limit infarction through reduction in myocardial oxygen demands, improvement in collateral blood supply and dissolution of coronary thrombus, to prevent in a later stage coronary reocclusion through administration of antiplatelet agents, and then to prevent infarct expansion through reduction in ventricular wall tension throughout the period of repair. Application of such an approach holds the promise of reducing infarct size and all the complications of infarction, as well as short and long-term mortality. The approach is active and aggressive, and contrasts with the approach applied a decade ago, where infarction was accepted as inevitable and therapies were reserved for managing its complications.

Adrenergic beta-Antagonists↗

Measurement of sulphated glycosaminoglycans and proteoglycan fragments in arthritic synovial fluid.

Immunoreactive proteoglycans (iPGs) and sulphated glycosaminoglycans (GAGs) were assayed in synovial fluid obtained from 22 patients with osteoarthritis (OA), 21 with rheumatoid arthritis (RA), 13 with gout, and five with Reiter's syndrome. A strong positive linear correlation was observed between concentrations of sulphated GAGs and iPGs in RA (r = 0.95) and gout (r = 0.94). A linear correlation was also observed in OA (r = 0.65). Patients with gout and Reiter's syndrome had significantly higher concentrations of sulphated GAGs and iPGs than patients with OA or RA. Patients with gout also had significantly higher total quantities of sulphated GAGs and iPGs in the knee joint cavity than patients with OA or RA. In all four diseases similar profiles were observed when comparisons were made between the total quantities and concentrations of sulphated GAGs and iPGs in synovial fluid. These results indicate that the observed differences in concentrations are not simply a function of dilution. The concentrations of sulphated GAGs and iPGs did not correlate closely with the type or number of inflammatory cells in the synovial fluid. Considerable variation was noted in the sulphated GAG/iPG ratios, suggesting that different mechanisms may be contributing to the release of proteoglycans in the diseases studied.

Adult↗

Using the OSCE to measure clinical skills performance in nursing.

The measurement of clinical skills performance continues to pose a challenge for nurse educators. This paper will report on the use of the objective structured clinical examination (OSCE) to measure the psychomotor learning outcomes of a programme designed to assist students to learn to conduct a nursing neurological examination. The OSCE has a tradition in medicine, having been developed by Ronald Harden in Scotland and first reported in the British Medical Journal in 1975. The University of Ottawa has the longest North American experience with this type of evaluation procedure and there is an increasingly rich medical literature referring to the OSCE. Although the OSCE appears to be a promising method for evaluating competence in the performance of clinical skills, there are no studies in the nursing literature examining the use of the OSCE as a method for evaluating the performance of clinical skills by nurses. Our experience suggests that the OSCE may be a powerful tool in the evaluation of clinical competence in nursing and that it may also be an effective facilitator for learning to perform clinical skills in nursing.

Clinical Competence↗

Pathogenesis of postoperative hyponatraemia following correction of scoliosis in children.

Eight paediatric patients undergoing major surgery for correction of scoliosis who were treated postoperatively with hypotonic saline and 5% dextrose have been studied. Plasma sodium, renin and aldosterone, and urine volume, sodium and osmolality were measured. These patients had an impaired ability to excrete a sodium-free water load. In the first 60 h urine volume remained reduced, while in the first 36 h urine sodium remained concurrently high. If the first 36 h postoperation are considered, the sodium-free water given was quantitatively retained and the serum sodium at 36 h was significantly correlated with the amount of free water given (P less than 0.01). To minimize postoperative hyponatraemia and the associated shift of water into the brain causing cerebral oedema, it is recommended that no more than 50 ml/kg sodium-free water be given until urine sodium falls and volume increases.

Adolescent↗

Rapidly progressive destructive arthropathy of the shoulder--a viewpoint on pathogenesis.

Two cases of rapidly progressive destructive shoulder arthropathy are described. Both patients were elderly women with generalized osteoarthropathy who had used forearm crutches for walking. Their shoulder disease was characterized by large, relatively painless effusions, low numbers of infiltrating leukocytes, biopsy evidence of mild inflammation, and radiological evidence of severe joint damage. Case 1 developed persistent drainage from a joint sinus, eventually necessitating arthrodesis. This complication has not previously been described in this condition. Hydroxyapatite crystals were demonstrated in the joint fluid in both cases but their pathological role is uncertain. We suggest that bearing weight through the upper limbs may hasten the development of degenerative arthritis in the shoulder, possibly by contributing to mechanical disruption of the rotator cuff.

Acute Disease↗