Search PubMed⌕ Search

Biomedical subjects

R Mackenzie

Publications and source records attributed to R Mackenzie.

At least 55 records · Page 3Linked to original sources

Measuring changes in quality of life following magnetic resonance imaging of the knee: SF-36, EuroQol or Rosser index?

Evidence suggests that magnetic resonance imaging (MRI) allows accurate diagnosis of meniscal and ligamentous injuries of the knee. However the link between improved diagnosis through MRI and improved patient quality of life (QOL) has yet to be shown. Previous studies aimed at establishing this link have found no significant improvements in health related quality of life (HRQOL) as measured by the Rosser classification and index. This paper presents the results of three HRQOL questionnaires (SF-36, Rosser and EuroQol) used to measure health change in 332 patients referred for MRI of the knee. Before imaging, patients reported poorer HRQOL than the general population on two of the three questionnaires (SF-36 and EuroQol). The same two questionnaires recorded significant improvements in patient health at six months, although patients' health had not yet reached that experienced in the general population. There was evidence to suggest that the index values attached to the Rosser classification made it unresponsive in this group of patients, which may have predisposed the null results of previous studies of the influence of MRI on HRQOL. Some evidence is provided to suggest that the EurolQol may be less responsive in assessing change in health status than the SF-36.

Adolescent↗

Errors at knee magnetic resonance imaging: true or false?

Amongst a series of 332 patients undergoing a prospective evaluation of the influence of magnetic resonance imaging (MRI) on diagnosis and outcome, arthroscopic correlation became available in 92 knees (91 patients). The MRI report, the arthroscopic findings and the patient's case notes were reviewed by a consensus panel. With respect to the menisci and cruciate ligaments, the formal radiological report was at variance with the arthroscopic findings in 22/349 sites where there had been no previous surgery (10 medial meniscus, six lateral meniscus and six anterior cruciate ligament). 12 of these 22 errors were considered, on review, to be genuine MRI errors. However, considerable controversy remains as to whether the other 10 "errors" were true or false. There are several factors which contribute to such controversy. These include technically difficult arthroscopies, delays between MRI and arthroscopy, and ambiguities in the wording of both the referral letter and the radiological report. These factors should be considered when evaluating the diagnostic performance of both MRI and arthroscopy.

Adolescent↗

Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system.

Human prostaglandin G/H synthase 1 and 2 were expressed in the baculovirus expression system and purified to high levels. Both enzymes were glycosylated. PGHS-1 appeared to be homogeneous by SDS-PAGE analysis but two closely migrating bands were detected in PGHS-2 preparation which were evidently due to heterogeneity in glycosylation. The amino-acid sequence of the N-termini of both isoforms indicated that the signal sequences were efficiently cleaved by the insect cells. The recombinant human PGHS-1 and PGHS-2 possessed both cyclooxygenase and peroxidase activities. Both had high affinities for arachidonate as substrate and underwent self-inactivation during catalysis. The recombinant isoforms were not pharmacologically identical, since some NSAIDs were selective inhibitors of either PGHS-1 or PGHS-2. This is the first report of high levels of expression and purification of human PGHS isoforms. The recombinant enzymes are invaluable in developing potent PGHS-2 selective inhibitors that may be efficacious anti-inflammatory drugs with no or low levels of toxicity.

Amino Acid Sequence↗

Quality of life assessments in the evaluation of magnetic resonance imaging.

Health technology assessments incorporating measurement of quality of life are becoming increasingly common. In the evaluation of magnetic resonance imaging (MRI), the most widely used quality of life instrument has been the Rosser classification. The theoretical basis for incorporating such a measure in the evaluation of imaging technology is considered and several studies using this instrument are reviewed. Despite the obvious technical advances of MRI and its influence on clinical management, it has proved difficult to demonstrate that the use of this expensive new imaging technique contributes to improvement in health-related quality of life. Some reasons why the expected improvement has not been demonstrated are discussed, as are the quality of life instruments which may be appropriate in this setting.

Communication↗

Direct anatomical-MRI correlation: the knee.

Cadaveric material is often used to guide and validate the interpretation of magnetic resonance imaging (MRI) studies. Direct correlation is achieved when the cadaver material is imaged and then directly sectioned in the plane of the image. Indirect correlation, where the cadaveric sections are compared with unrelated in-vivo images, is easier and more commonly used. Technical difficulties associated with the direct method include preservation of form and composition of the tissues, and the choice of the correct location and plane in which to section the cadaver. Using an MRI compatible ruler, designed to assist the direct correlation of MRI and cadaveric sections, we have examined 10 preserved (embalmed) cadaveric knees using different MRI sequences on several occasions. Despite these variations, subsequent sectioning of the cadaveric knees has shown good correlation with the MR images. Of 54 MR images compared with cadaveric sections, anatomical correlation was rated by independent observers as good or perfect in 47 (87%). This new, versatile and simple method can make better use of our preserved human cadaveric material and has potentially wide application; we are now developing it further to assess the technical capabilities of novel imaging sequences.

Aged↗

Human peritoneal mesothelial cell prostaglandin synthesis: induction of cyclooxygenase mRNA by peritoneal macrophage-derived cytokines.

Increasing evidence suggests that the mesothelial cell contributes to the control of inflammation in both the normal and inflamed peritoneal cavity. The present study examines the regulation of prostaglandin production by human peritoneal mesothelial cells (HPMC) following stimulation with peritoneal macrophage-conditioned medium and the cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). IL-1 beta and TNF-alpha stimulated significant release of prostaglandin above background levels in a time and dose dependent manner. Stimulation of HPMC with IL-1 beta (500 pg/ml) or TNF-alpha (100 pg/ml) for 24 hours resulted in the release of 24.5 +/- 4.3 (N = 11) (z = 3.40, P < 0.001 vs. control) and 19.4 +/- 4.5 (N = 10; z = 3.29, P < 0.001 vs. control) pg 6-keto-PGF1 a/micrograms cellular protein, respectively. Pretreatment of HPMC with dexamethasone (10(-6) to 10(-9) M) inhibited both constitutive and cytokine stimulated prostaglandin synthesis in a dose dependent manner. Both PMø-CM and PMø-S.epiCM stimulated 6-keto-PGF1 alpha and PGE2 synthesis by HPMC in a time and dose dependent manner (PMø-S.epiCM >> PMø-CM). Co-incubation of HPMC with PMø-S.epiCM in the presence of anti-IL-1 beta and/or anti-TNF-alpha antibody, interleukin-1 receptor antagonist or soluble TNF receptor (TNF p75) significantly reduced the capacity of these supernatants to stimulate prostaglandin synthesis. Exposure of HPMC to cytokines or PMø-S.epiCM resulted in the time dependent increase in the levels of both Cox-1 and Cox-2 mRNA as assessed by RT/PCR analysis with the greatest increase being seen for Cox-2. These data demonstrate specific stimulation of eicosanoid metabolism in HPMC by peritoneal macrophage derived cytokines, indicating the possible importance of these mediators in the activation of intraperitoneal prostaglandin synthesis. HPMC prostaglandins might act as important pro/anti-inflammatory mediators contributing to a cytokine network in the peritoneal cavity during CAPD peritonitis.

Base Sequence↗

Computed tomography or magnetic resonance imaging for axillary symptoms following treatment of breast carcinoma? A randomized trial.

Fifty-eight patients presenting with axillary symptoms (pain, oedema, etc) following radiation therapy for breast carcinoma were randomized to be investigated by either computed tomography (CT: 29 patients) or magnetic resonance imaging (MRI: 28). The objectives of the study were to compare the efficacy of the two tests in identifying the presence of tumour and their effectiveness as judged by quality of life (QOL) outcome measurements. Both tests proved efficacious; the predictive values for a positive result (tumour present) were 100% for both tests; the predictive values for negative findings were in the range of 76 to 90% for CT and 81 to 100% for MRI. As regards outcome, complete QOL data were available in 37 patients (17 of these patients had CT, 20 MRI). Although the mean change in QOL over 6 months was slightly more favourable in the patients investigated by MRI than in the CT group, the difference did not reach statistical significance.

Aged↗

Magnetic resonance imaging of the knee: does foot restraint improve the examination?

Involuntary movement by the patient can cause severe artefacts in magnetic resonance imaging of the knee. We have designed and constructed a device that immobilizes the foot, and thereby the knee. In this way the knee still remains accessible for the application of a variety of surface coils. A retrospective subjective analysis was performed of the magnetic resonance images from a control group of 23 patients who were examined without the restraint device and a study group of 26 patients in whom the device was used. The differences in the central tendency of subjective scores between the control and study groups were not significant for either motion artefact or anatomical conspicuity. However, in terms of dispersion the observed reduction in the study group was significant for anatomical conspicuity (p < 0.05) and almost significant for motion artefact (p < 0.10). These findings suggest that the restraint device may improve image quality by eliminating some of the worst motion artefacts. The device also significantly improves positioning of the knee in relation to the magnet isocentre (p < 0.01).

Adolescent↗

Down-regulation of cyclooxygenase product generation by human peritoneal macrophages.

Isolated human peritoneal macrophages under resting conditions synthesize and release significant quantities of the cyclooxygenase products prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). These increased linearly with time and were dependent on de novo protein synthesis. Following the addition of calcium ionophore A23187 there was a marked decrease in total generation of immunoreactive cyclooxygenase products. In contrast, there was a concomitant increase in the release of 5-lipoxygenase products. The down-regulation of both PGE2 and TXB2 was not due to diversion of substrate from the cyclooxygenase pathway to the 5-lipoxygenase pathway nor was it due to inhibitory effects of products of the 5-lipoxygenase pathway on the generation of cyclooxygenase products. Instead, the inhibitory effects of A23187 were thought to be due to a down-regulation of cyclooxygenase itself, a hypothesis supported by the finding that TXA2 synthase proved to be unaltered and Western analysis of crude peritoneal macrophage (PM phi) membranes demonstrated lesser quantities of cyclooxygenase in membranes from A23187-treated PM phi than in those prepared from control cells.

Adult↗

In vitro testing of a potentially biocompatible continuous ambulatory peritoneal dialysis fluid.

In the present study a newly formulated dialysis solution (HDF) was tested for its effects on phagocyte viability and function as well as its ability to support bacterial growth. This solution differs from standard CAPD solution (NPD) by the inclusion of histidine to buffer the fluid to pH 6.7. Low-dextrose HDF (1.36% w/v dextrose) did not significantly decrease the viability or inhibit any of the PMN functional parameters measured (phagocytosis, LTB4 release or respiratory burst activation) when compared to control buffer. NPD (1.36% w/v dextrose) at low pH as well as all high-dextrose dialysis solutions (NPD and HDF) significantly inhibited most PMN functions independently of reduced viability. Peritoneal mesothelial cell viability was unaffected by either low- or high-dextrose HDF but was significantly reduced by NPD (1.36 and 3.86% dextrose) at pH 5.2. The inhibitory effects of low dextrose dialysis solutions were confirmed as being partly related to their low initial pH. High-dextrose dialysis fluids, however, inhibit PMN function by a mechanism which, in addition to initial pH, appears to be directly related to their dextrose content but not their osmolality.

Bacteria↗

Type 1 fimbriate strains of Escherichia coli initiate renal parenchymal scarring.

The renal scarring which characterizes chronic pyelonephritis is initiated by bacterial infection and is independent on the activation of an inflammatory response. Although the presence of polymorphonuclear leukocytes (PMN) is essential for initiating the scarring process, the bacterial structures responsible for their activation have not been investigated. In an animal model of chronic pyelonephritis the surface area of the renal scars produced by Type 1 fimbriate escherichia coli (E. coli) was significantly greater than that of those produced by P fimbriate and non-fimbriate strains (P less than 0.01). The activation of human PMN by the same Type 1 fimbriate organisms resulted in a significant release of lysosomal neutral protease activity (P less than 0.001) and activation of the respiratory burst (P less than 0.01). The neutral protease release in response to P fimbriate and non-fimbriate organisms was not significantly increased. The extent of renal scarring also correlated with the release of neutral protease activity (P less than 0.02) and with the degree of activation of the respiratory burst (P less than 0.05). These results demonstrate that the ability of E. coli strains to cause renal scars may be related to their capacity to express Type 1 fimbria, which may be a causative factor in the in vivo activation of the inflammatory response.

Animals↗

A patient with insulinoma presenting for psychiatric assessment.

A case of insulinoma referred for psychiatric assessment illustrates the need for a high index of suspicion of organic mental disorder even in patients who have undergone previous extensive medical investigation. The diagnostic difficulties illustrate the need for persistence and cooperation between specialists in such cases.

Adenoma, Islet Cell↗