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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cross-sectional analysis of the differences between patients with systemic lupus erythematosus in England, Brazil and Sweden.

This study is a cross-sectional analysis of the differences between SLE outpatients seen in Rheumatology departments at University centres in England, Brazil and Sweden, using a standard protocol. The demographic characteristics, extent and activity of disease of 209 patients with SLE were studied; 112 patients were seen in England, 33 in Brazil and 64 in Sweden. The median age of disease onset of Brazilian and English patients was 25 years and of Swedish patients 31.5 years. Disease activity was measured by the BILAG index. In most systems Brazilian patients experienced more activity than English patients and English patients more activity than Swedish patients. Non-Caucasians experienced more active disease than Caucasians. No sex or occupational differences were observed in disease activity. English patients were the most likely to have experienced photosensitivity, oral ulcers and haematological disorders, Brazilian patients renal disorders and Swedish patients discoid rashes. Brazilian patients were the most likely to be prescribed only one drug for treatment of SLE and to be taking steroids and the highest dose of steroids, in contrast to the European patients who were often prescribed steroids and an antimalarial agent or azathioprine. The results of this cross-sectional assessment of disease activity using a standardized instrument indicate that there are real differences in the extent and degree of activity of SLE in different national groups. This reflects a combination of genetic, environmental and social influences on disease expression and has implications for treatment and monitoring of SLE patients.

Adolescent↗
PubMed1994

The role of continuous background infusions in patient-controlled epidural analgesia for labor and delivery.

The use of a background infusion with intravenous patient-controlled analgesia (IV-PCA) increases drug consumption without any additional contribution to analgesia. There are no data on the potential advantage of a background infusion administered with patient-controlled epidural analgesia (PCEA) for labor and delivery. Sixty women were randomized to one of four groups and received either: (a) demand dose PCEA (demand dose = 3 mL; lockout interval = 10 min); (b) continuous infusion plus demand dose PCEA (two separate infusion rates: 3 mL/h and 6 mL/h); or (c) a fixed-rate continuous epidural infusion (CEI) at 12 mL/h. All patients received 0.125% bupivacaine with 2 micrograms/mL of fentanyl. The study protocol was double-blind and placebo-controlled. Visual analog pain scores, motor strength, and bilateral pinprick analgesia were assessed every half hour by a blinded observer. Pain scores, cephalad extent of sensory analgesia, and motor block were no different among the study groups during the first and second stages of labor. Cumulative hourly bupivacaine use was similar among all PCEA study groups. However, use of PCEA (in whatever mode) provided a 35% dose-sparing effect in comparison to CEI. The PCEA groups receiving no background infusion or a 3-mL/h background infusion had a greater need for physician-administered supplemental bupivacaine during the first stage of labor. While not statistically significant, a trend toward increased need for supplementation was seen in these same patient groups over the entire course of labor and delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clinical pharmacology and modification of autoimmunity and inflammation in rheumatoid disease.

The increased understanding of the mechanisms which underlie rheumatoid disease has been accompanied by a more appropriate use of the limited repertoire of therapeutic agents. Conventional second-line drugs still have a role in everyday practice. The efficacy of these agents in reducing the severity of clinical signs of joint inflammation, whilst at the same time causing significant reductions in the laboratory measures of the acute phase response is undoubtedly confirmed by meta-analysis of several therapeutic trials of these agents. Whether or not these agents can influence outcome, usually assessed in terms of radiological progression, is more contentious. Furthermore, their toxicity in long term use is not inconsiderable. However, newer agents may play a more important part in therapy in the future. Such therapy can be designed to specifically interfere with the abnormalities of the immune system which characterise rheumatoid arthritis. Many of the agents reviewed have been successfully applied to animal models of arthritis but we still await large randomised controlled studies in humans to determine their clinical efficacy and toxicity. In view of the complexity of the immunological abnormalities in rheumatoid arthritis, it may be necessary to consider using a number of such agents in any particular patient. This should result in more rational therapy in rheumatoid arthritis.

Animals↗
PubMed1994

Sulfasalazine induced seizures and dysphasia.

We describe the case of a 46-year-old woman with rheumatoid arthritis who developed a severe reaction to sulfasalazine, characterized by dysphasia, seizures, rash and the development of strongly positive pANCA (perinuclear antineutrophil cytoplasmic antibodies). Her condition improved spontaneously upon withdrawal of sulfasalazine. Dysphasia has not been reported as a side effect of sulfasalazine.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1994

Influence of a lymph node environment on invasiveness of metastatic tumor cells.

BACKGROUND: We investigated the possibility that lymph nodes might increase metastatic efficiency of tumor cells lodged there by measuring changes in tumor cell invasiveness after physical contact with an in vitro approximation of a lymph node environment. STUDY DESIGN: The experimental model involved growing Lewis lung carcinoma (LL) or B16 melanoma cells on microcarrier beads, rolling them on a "lymph node endothelial surface," which was created by growing endothelial cells on a differentiating acid extract of lymph node biomatrix, and testing the ability of those tumor cells to invade across matrigel-coated filters at rest (buffer) and in response to a chemotactic stimulus (3T3 conditioned media). RESULTS: Compared with contact with plastic, LL invasiveness was increased fivefold (buffer or conditioned media) and B16 invasiveness fourfold (conditioned media). Tumor cell invasiveness was not increased by exposure to the acid extract of biomatrix alone. Invasiveness to buffer or conditioned media after exposure to endothelial cells alone was 70 and 54 percent (LL) and 42 and 80 percent (B16), respectively, of the invasiveness induced by exposure to both. Compared with invasiveness induced by exposure to lymph node (100 percent), exposure to a "lung endothelial surface" induced invasiveness of 63 and 85 percent (LL) and 40 and 52 percent (B16) to buffer and conditioned media, respectively. Exposure to a hepatic endothelial surface induced invasiveness similar to that induced by lymph node; 90 and 82 percent (LL) and 110 and 86 percent (B16) of lymph node-induced invasiveness. CONCLUSIONS: A lymph node environment may modulate the metastatic potential of tumor cells.

Animals↗
PubMed1993

Defective mitosis due to a mutation in the gene for a fission yeast 26S protease subunit.

We have isolated a mutant, mts2, in the fission yeast Schizosaccharomyces pombe which is defective in chromosome segregation. The predicted amino-acid sequence of the cloned mts2+ gene product is 75% identical to the S4 subunit of the human 26S ATP/ubiquitin-dependent protease. The human S4 subunit complementary DNA expressed from an S. pombe expression plasmid can rescue an S. pombe mts2 gene disruption. Both observations demonstrate that the mts2+ gene is the S. pombe homologue of the human S4 subunit. In addition, we provide genetic evidence for a physical interaction between the S4 and the related S7 subunit in the 26S multiprotein protease. We show that polyubiquitin-conjugated proteins accumulate in the mts2 mutant at the restrictive temperature, demonstrating that the mutant has an in vivo defect in the ubiquitin-dependent proteolysis pathway. Finally, the phenotype for the mts2 mutant indicates that protein degradation by the 26S protease is essential not for entry into but for the completion of mitosis.

Amino Acid Sequence↗
PubMed1993

The cell cycle genes cdc22+ and suc22+ of the fission yeast Schizosaccharomyces pombe encode the large and small subunits of ribonucleotide reductase.

The cdc22+ gene of Schizosaccharomyces pombe is required early in the cell cycle, and its transcript varies in concentration in step with the cell cycle, with a peak level at the G1-S boundary. The sequences of the cdc22+ gene and of a multicopy suppressor of cdc22ts mutations, suc22+, have been determined. The cdc22+ open reading frame, which is interrupted in the genome by a single intron very close to its 5' end, encodes a protein of 811 amino acids, which has an amino acid sequence highly similar to that of the large subunit of ribonucleotide reductase from several species. The suc22+ gene contains an uninterrupted open reading frame of 391 amino acids, very similar to the sequence of the small subunit of ribonucleotide reductase. Disruption of either gene is lethal. Upstream of the cdc22+ coding region are seven short sequence elements similar to the recognition sequence for MluI, which are involved in regulating periodic transcription of the gene. Inhibition of DNA synthesis by hydroxyurea results in a several-fold increase in the level of the cdc22+ transcript. In contrast, hydroxyurea does not induce the 1.5 kb transcript of suc22+, but results in the induction of a 1.9 kb mRNA which hybridises to suc22+ DNA.

Amino Acid Sequence↗
PubMed1993

Symbolic decision support in medical care.

Symbolic decision procedures offer a flexible alternative to classical quantitative procedures for decision making, particularly when precise parameters (such as probabilities) are hard to estimate. One such procedure, based on a logic of argumentation, is described. Specifications of inference methods for such functions as proposing and refining decision options, deducing and inheriting arguments for and against options, and selecting among alternatives are presented. These exploit declarative models for patient data, domain and task knowledge. A simple method for translating the specifications into executable Prolog is described. A practical and efficient toolset for using the procedure in a wide range of clinical environments is being developed within the DILEMMA project of the European Commission's Advanced Informatics in Medicine research programme.

Databases, Factual↗
PubMed1993

Relationship between serum butyrylcholinesterase activity, hypertriglyceridaemia and insulin sensitivity in diabetes mellitus.

1. The activity of serum butyrylcholinesterase ('pseudocholinesterase', EC3.1.1.8) was investigated in 56 patients with type 1 diabetes mellitus, 51 patients with type 2 diabetes mellitus and 101 healthy control subjects. 2. Butyrylcholinesterase activity was significantly elevated in both type 1 (8.10 +/- 3.35 units/ml) and type 2 (7.22 +/- 1.95 units/ml) diabetes compared with the control subjects (4.23 +/- 1.89 units/ml) (P < 0.001). 3. In the patients with type 1 and type 2 diabetes, serum butyrylcholinesterase activity was correlated with log serum fasting triacylglycerol concentration (r = 0.41 and r = 0.43, respectively, P < 0.001). In the type 2 population serum butyrylcholinesterase activity was also correlated with insulin sensitivity (r = -0.51, P < 0.001). 4. Serum butyrylcholinesterase activity was unrelated to age, gender, serum gamma-glutamyltranspeptidase activity, body mass index, or treatment for diabetes in both the diabetic populations. 5. In 37 non-diabetic patients with butyrylcholinesterase deficiency serum triacylglycerol levels were in the normal range. 6. These results are consistent with the view that butyrylcholinesterase may have a role in the altered lipoprotein metabolism in hypertriglyceridaemia associated with insulin insensitivity or insulin deficiency in diabetes mellitus.

Butyrylcholinesterase↗
PubMed1993

Diet treatment of newly presenting type 2 diabetes improves insulin secretory capacity, but has no effect on insulin sensitivity.

Fifteen newly diagnosed obese Type 2 diabetic subjects were treated with diet alone for 3 months with a median 1.5 kg weight loss. Each had a Continuous Infusion of Glucose with Model Assessment (CIGMA) test, at diagnosis and at 3 months, measuring insulin and C-peptide responses, and deriving mathematically modelled measures of beta-cell function and insulin sensitivity. Median fasting glucoses were 9.6 mmol l-1 at diagnosis and 8.5 mmol l-1 at 3 months (NS). Median fasting insulin was 9.3 mU l-1 at diagnosis and 11.7 mU l-1 at 3 months (NS). Median fasting C-peptide was 0.58 nmol l-1 at diagnosis and 0.64 nmol l-1 at 3 months (p < 0.05). Median achieved plasma insulin increased from 13.8 mU l-1 at diagnosis to 17 mU l-1 at 3 months (p < 0.02); median achieved plasma C-peptide increased from 0.72 nmol l-1 at diagnosis to 0.81 nmol l-1 at 3 months (p < 0.002). Modelled beta-cell function rose from median 26% at diagnosis to 37% at 3 months (p < 0.02). Modelled insulin sensitivity showed no significant change (median 0.31 at diagnosis, 0.27 at 3 months, NS). Elevation of achieved C-peptide was positively correlated with weight loss (Rs = 0.53, p < 0.05), but not with change in fasting glucose. Diet treatment of newly diagnosed Type 2 diabetes, with modest weight loss, results primarily in improvement of insulin secretory capacity, rather than insulin sensitivity.

Adult↗
PubMed1993

Assessment of lupus: where are we now?

Decisions about treatment for patients with SLE are based on numerous criteria, including the rate of change of clinical features and disease markers (especially antibodies to dsDNA and markers of complement turnover), which organ systems are affected, the severity of manifestations, and the presence of pre-existing damage (which may reduce the reserve capacity of the organ system). Most of the currently available organ systems calculate a single overall score, at a single point in time, and take few of these considerations into account. SLAM is the only index to consider directly the scoring of severity as well as activity, though this concept is probably inherent in most of the other indices because of various methods for weighting the scores. Preliminary studies have indicated that four of the scales (BILAG, SLAM, LAI, and SLEDAI) are sensitive to change. Few of the indices have been tested longitudinally, hence their role in clinical trials remains to be established. None of the indices considers the impact of damage, indeed this is not their remit, but this concept is being considered by an international working group. Outcome in SLE has been shown to be determined by, among other things, the number of exacerbations and the presence of renal or neurological disease. It would seem, therefore, important to measure disease activity in designated organ systems, which most of the indices fail to do. The inclusion of immunological tests in some scales (for example, SIS, SLEDAI, LAI) makes them unsuitable for use as instruments to validate immunological or other scatological markers. Furthermore, given the heterogeneity of disease manifestations in SLE, and evidence linking scatological abnormalities with specific clinical manifestations, it is perhaps naive to expect a new scatological test to correlate strongly with overall disease activity. Three of the currently available activity scales have been shown to be reliable, both between and within raters (BILAG, SLAM, SLEDAI). The lack of a 'gold standard' for measuring disease activity in SLE makes it difficult to be sure that these scales are actually measuring what they are supposed to be measuring (criterion validity), but they do correlate strongly with each other in cross sectional studies, suggesting that they are, at least, all measuring the same thing (convergent validity). Convergent validity for these instruments used longitudinally remains to be established, particularly for patients with very active disease. In conclusion, measurement of disease activity in SLE is central to patient care, and a number of instruments are available fro this purpose. Although none is perfect, most are reliable and valid, and are suitable for classifying and monitoring groups of patients in the research setting. In reality, the indices are used with the additional benefit of laboratory markers and, as yet, no one has found the instruments sufficiently sensitive and specific to rely entirely upon them. The exact choice of instrument should be governed by the purpose for which it is required in clinical practice. Disease activity scales are unlikely to be appropriate for dictating treatment decisions in individual cases. An instrument which would be comprehensive and flexible enough for this purpose would necessarily prove too complicated and cumbersome for widespread use.

Acute Disease↗
PubMed1993

Comparison of three techniques for body composition analysis in cystic fibrosis.

Body composition analysis is an important component of nutritional assessment in cystic fibrosis (CF). No gold standard of measurement exists, and techniques applicable to healthy populations may be unsuitable for CF patients. We assessed lean body mass (LBM) in 12 children with CF by skinfold (SK) measurements, bioelectrical impedance analysis (BIA), and dual-photon absorptiometry (DPA) and repeated these measures in 10 subjects 6 mo later. SK and DPA measures in eight older CF patients and eight healthy controls were compared to evaluate any effect of disease on estimates of LBM by use of DPA. Good agreement between the measures was seen at baseline and 6 mo by use of concordance plots. However, the limits of agreement between measures ranged up to 19% of SK-derived LBM measures (baseline: SK and DPA, 2.63 to -3.93 kg; SK and BIA, 2.36 to -1.24 kg; BIA and DPA, 1.88 to -4.28 kg; 6 mo: SK and DPA, 2.10 to -3.58 kg; SK and BIA, 6.28 to -5.49 kg; BIA and DPA, 5.53 to -7.79 kg). The change in LBM over 6 mo did not correlate among the three measures. Only BIA change in LBM correlated with weight change (r = 0.716, P < 0.02), probably due to the inclusion of weight in the regression equations for determining LBM from impedance. The relationship between SK and DPA measures did not differ between the CF and control groups, suggesting that there was no effect of disease on the DPA measure. The results suggest that none of these methods is precise enough to follow short-term changes in the nutritional status of CF patients longitudinally.

Absorptiometry, Photon↗
PubMed1993

The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus.

The British Isles Lupus Assessment Group (BILAG) index is a computerized index for measuring clinical disease activity in systemic lupus erythematosus (SLE), which was developed according to the principle of the physician's 'intention to treat'. The index allocates separate alphabetic scores to each of eight organ-based systems; a total score is not calculated. This study demonstrated good between-rater reliability for the BILAG index for each organ-based system. There was no evidence of bias between observers. The BILAG index had good overall sensitivity (87%) and specificity (99%) when compared with the 'gold standard' criterion (starting or increasing disease-modifying therapy). There were high positive predictive values overall (80%), and for each organ-based system, with the exception of the neurological system.

Adolescent↗
PubMed1992

Abnormal sulphur oxidation in systemic lupus erythematosus.

S-carboxy-L-methylcysteine was used to assess the activity of the S-oxidation pathway of sulphur metabolism in 35 patients with systemic lupus erythematosus (SLE); 25 (71%) showed impaired sulphoxidation and 21 (60%) produced virtually no sulphoxides, compared with 17 (36%) and 2 (4%), respectively, of 47 healthy controls. The substrate/product ratio of cysteine oxygenase (plasma cysteine/sulphate) was significantly higher in SLE patients than in controls (median [interquartile range] 362 [224-588] vs 65 [44-111]; p less than 0.00001). The alternative pathway of sulphur metabolism, S-methylation, catalysed by thiolmethyltransferase, was not impaired in the SLE patients. There is a biochemical difference in sulphur metabolism between SLE and rheumatoid arthritis, since both pathways are impaired in the latter disorder.

Adult↗
PubMed1992

Elevated plasma insulin-like growth factor binding protein-1 levels in type 1 (insulin-dependent) diabetic patients with peripheral neuropathy.

Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between plasma IGF-I, IGFBP-1, glucose and insulin in Type 1 (insulin-dependent) diabetic patients with peripheral polyneuropathy. Plasma samples were taken at hourly intervals over an 11-h period (08.00-19.00 hours) in order to characterise secretory profiles for 15 Type 1 diabetic patients (eight neuropathic and seven non-neuropathic) and eight non-diabetic control subjects. In the non-diabetic subjects, mean plasma IGF-I levels were stable throughout the 11-h period with a range of 97 micrograms/l-169 micrograms/l. In contrast, mean plasma IGFBP-1 levels declined steadily from a high level of 1.99 micrograms/l at 08.00 hours to approximately one half (0.86 microgram/l) at 15.00 hours. Comparison of areas under the curves revealed significant negative correlations between IGFBP-1 and glucose (-0.88, p = 0.01), IGFBP-1 and insulin (-0.75, p = 0.016), and IGFBP-1 and IGF-I (-0.68, p = 0.03). A significant positive correlation was found between insulin and IGF-I (+0.89, p = 0.001). The diabetic patients had markedly elevated plasma IGFBP-1 levels (area under curve, p = 0.01) and lower plasma IGF-I levels (p = 0.033) even though these patients were hyperinsulinaemic throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Antibodies to protein P in systemic lupus erythematosus.

A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.

Antibodies↗