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Biomedical subjects

K G Couchman

Publications and source records attributed to K G Couchman.

18 recordsLinked to original sources
PubMed2000

A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree.

Malignant hyperthermia (MH) is a pharmacogenetic disorder that predisposes to a sometimes fatal hypermetabolic reaction to halogenated anaesthetics. MH is considered to originate from abnormal regulation of skeletal muscle Ca(2+) release. Current diagnosis of MH susceptibility (MHS) relies on in vitro contracture testing (IVCT) of skeletal muscle. The ryanodine receptor (RYR1) encoding the major Ca(2+) release channel in the skeletal muscle sarcoplasmic reticulum has been shown to be mutated in a number of MH pedigrees. The large Maori pedigree reported here is the largest MHS pedigree investigated to date and comprises five probands who experienced clinical episodes of MH and 130 members diagnosed by the IVCT. Sequencing of the 15 117 bp RYR1 cDNA in a MHS individual from this pedigree identified a novel C14477T transition that results in a Thr4826 to Ile substitution in the C-terminal region/transmembrane loop of the skeletal muscle ryanodine receptor. This is the first mutation in the RyR1 C-terminal region associated solely with MHS. Although linkage analysis showed strong linkage (max LOD, 11.103 at theta = 0.133) between the mutation and MHS in the pedigree using the standardized European IVCT phenotyping protocol, 22 MHS recombinants were observed. The relationship between the IVCT response and genotype was explored and showed that as IVCT diagnostic cut-off points were made increasingly stringent, the number of MHS discordants decreased with complete concordance between the presence or absence of the C14477T mutation and MHS and MH normal phenotypes, respectively, using a cut-off of 1.2 g tension at 2.0 mM caffeine and 1.8 g tension at 2.0% halothane. Many MHS pedigrees investigated have been excluded from linkage to the RYR1 gene on the basis of a small number of recombinants; however, the linkage analysis reported here suggests that other recombinant families excluded from linkage to the RYR1 gene may actually demonstrate linkage as the number of members tested within the pedigrees increases. The high number of discordants observed using the standardized diagnostic cut-off points is likely to reflect the presence of a second MHS susceptibility locus in the pedigree.

Amino Acid Sequence↗
PubMed1992

Propofol is a 'safe' anaesthetic agent in malignant hyperthermia susceptible patients.

In this study we investigated in vitro and in vivo effects of propofol in malignant hyperthermia susceptible (MHS) patients in order to assess the safety of propofol infusion as a non-triggering anaesthetic technique for diagnostic and therapeutic procedures. In vitro, human MHS muscle samples were exposed to propofol and changes in (a) baseline tension and (b) contracture tension on exposure to halothane and caffeine were measured. In vivo, (a) anaesthesia was induced in ten muscle biopsy positive MHS patients with propofol 2.5 mg/kg and (b) anaesthesia was produced in five muscle biopsy positive MHS patients with infusions of propofol up to 10 mg/kg/hr. In vitro, human MHS muscle did not develop contractures with propofol alone. Propofol had no significant effect on contracture development in response to halothane and caffeine. In vivo, no evidence of an MH response was detected following induction or maintenance of anaesthesia with propofol. Our results and literature review are in agreement that propofol is a 'safe' induction and maintenance agent in MHS patients. Propofol can be used for muscle biopsy anaesthesia because it does not alter the sensitivity of diagnostic muscle biopsy testing.

Adolescent↗
PubMed1991

Rheumatic disease in a Philippine village. II: a WHO-ILAR-APLAR COPCORD study, phases II and III.

Many difficulties were encountered in a population survey of rheumatic complaints in a remote village area in the Philippines affecting the reliability of estimates of population prevalence. In phase I, a simple questionnaire identified 269 adults out of 950 who had rheumatic symptoms. In Phase II, 234 or 87% of positive respondents were requestioned using a more detailed pro forma. There were 196 with peripheral joint pain, 67 with neck pain and 137 with back pain. One third attributed their symptoms to work and 127 subjects had to stop work because of their complaints. Disability, including an inability to carry loads, affected nearly 1.8% of the population. Questions designed to detect rheumatoid arthritis and gout were not satisfactorily answered. Of those with complaints, 82% indicated that they still required help for their symptoms. In phase III, 166 subjects were medically examined. Osteoarthritis of the knee was found in 25 and 17 had Heberden's nodes. There were 16 with epicondylitis; 16 had rotator cuff pain and 35 had levator scapulae insertion pain. Three of these and three others had neck or shoulder swellings related to carrying loads on poles. Definite rheumatoid arthritis was diagnosed in two subjects and gout in five. No case of ankylosing spondylitis was identified. Thus, rheumatic complaints were common in this rural community and were frequently severe enough to cause disability and loss of time from work. Health worker education is required on how to handle these problems.

Adolescent↗
PubMed1990

Rehabilitation in chronic back pain: employment status after four years.

Of 129 chronic back pain patients treated consecutively at the Palmerston North hospital rehabilitation unit in 1982-3, 102 responded to a questionnaire in 1987. The 27 nonresponders had had pain for a shorter time and were considered to have a better prognosis. Of the 102 responders, 31 no longer had back pain; 51 (six women) were employed full or part time and 17 (two women) were looking for work. Two men had reversed roles and 17 had retired. Women who no longer had a job outside the home classed themselves as housewives rather than as retired or unemployed. This study provides data for future planning but without controls, confident conclusions cannot be drawn on the efficacy of the rehabilitation programme. There is a need for further controlled studies.

Adolescent↗
PubMed1987

What's happened to catabolin?

Unlike other areas of research into arthritis, it is pleasing to record independent work leading to convergence of ideas instead of divergence and increasing complexity. Catabolin is now identified with interleukin-1, although there is case for the retention of the original name to describe its chondrocyte-stimulating function with subsequent matrix degradation. In 10 years, catabolin/interleukin-1 research has yielded much information about cellular interactions within the arthritic joint and has provided a probe with which the intricacies of matrix metabolism are being unravelled. In future, there are prospects of characterizing the naturally occurring inhibitors and developing new compounds which influence the actions of catabolin/IL-1 to the benefit of the patient with arthritis.

Animals↗
PubMed1986

The effect of anti-rheumatic drugs on factors from porcine synovium inducing chondrocyte mediated cartilage degradation.

A selection of NSAID's and diphosphonates were studied in a tissue culture model of cartilage degradation utilising porcine synovium and bovine nasal cartilage. All the NSAID's significantly reduced cartilage degradation when incorporated into the synovial culture medium. Lesser reductions were recorded when preformed chondrocyte stimulating factors were used and NSAID's added at the cartilage assay stage. These findings suggested that the principle site of action of NSAID's is upon the production of chondrocyte stimulating factors. None of the NSAID's tested affected inherent cartilage degradation. Diphosphonates had the opposite effects, they increased inherent cartilage degradation but had no effect on chondrocyte mediated cartilage degradation. The relationship of these results to previous known effects of NSAID's and diphosphonates upon cartilage is discussed. In addition, correlations between chondrocyte stimulating factors, catabolin and interleukin 1 are made.

Animals↗
PubMed1986

Experience with isoxicam and catabolin.

1 Synovial cells produce a protein factor, catabolin, that induces chondrocytes to resorb their own matrix with the release of glycosaminoglycan (GAG). 2 Studies were performed to determine the effect of isoxicam, a new NSAID, on GAG production in a catabolin system utilizing tissue culture of bovine nasal septum in a medium containing pooled synovial tissue from young pigs. 3 Using fresh medium containing no synovial tissue, the release of GAG by inherent cartilage breakdown was 49.7% after 8 days culture. GAG release at 8 days increased to 83.6% by the addition of synovial cells to the culture medium, due to the action of catabolin. 4 The incorporation of isoxicam, at concentrations from 5-30 micrograms ml-1, in the porcine synovial culture medium significantly reduced the GAG release to 70.9%. 5 Isoxicam at 50 micrograms ml-1 added to fresh medium without synovial tissue had no effect on cartilage breakdown or GAG production. 6 The results of these experiments show that isoxicam is unlikely to impair cartilage metabolism and may even decrease cartilage resorption.

Animals↗
PubMed1977

Degenerative arthritis in mice. Study of age and sex frequency in various strains with a genetic study of NZB/B1, NZY/B1, and hybrid mice.

Of a number of strains of mice studied for evidence of autoimmunity, NZY/B1 mice showed the highest frequency of degenerative arthritis of the knee, reaching a maximum of 68% at 18 months. 50% PN mice were affected at 24 months. Both breeds differed from previously described strains in not showing a sex difference. The NZB/B1 mice were rarely affected and hybrids to the NZY and the backcross to the NZB showed a recessive pattern of inheritance for knee arthritis and an additive pattern for carpal arthritis. Polygenic inheritance was postulated as at least three genes would be necessary to explain the findings. Joint disease was not related to red cell and nuclear antibodies, glomerulitis, or arteritis.

Age Factors↗
PubMed1975

Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice.

Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation.

Age Factors↗