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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 19 recordsLinked to original sources

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

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

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

Urinary IL-6: a marker for mesangial proliferative glomerulonephritis?

A prospective study of plasma and urinary interleukin-6 (IL-6) levels was performed in 54 patients undergoing renal biopsy to determine whether detectable urinary IL-6 was a reliable marker for mesangial proliferation. Interleukin-6 was found in both the urine and plasma of seven patients, the urine alone of 15 patients, and the plasma alone of two patients. Interleukin-6 was not detected in the urine or the plasma of the remaining 30 patients, the urine of 10 healthy controls or the urine of 10 patients with rheumatoid arthritis with raised plasma IL-6. Interleukin-6 was found in the urine of only one out of an additional seven patients with lupus nephritis. Urinary IL-6 was associated with a variety of renal abnormalities and was not restricted to those with mesangial hypercellularity. Furthermore, many patients with mesangial hypercellularity did not have detectable urinary IL-6. There was no correlation between urinary IL-6 and plasma IL-6, urinary albumin excretion or urinary creatinine. These results suggest that IL-6 detected in the urine is a marker of renal IL-6 production, but not specifically of mesangial hypercellularity. The patients with IL-6 in the urine had a mean serum creatinine significantly higher than those without IL-6. It is not possible to distinguish at present whether IL-6 contributes to renal dysfunction or whether it reflects renal damage.

Adolescent

Accuracy of measurements of small changes in soft tissue mass by use of dual-photon absorptiometry.

Dual-photon absorptiometry (DPA) has recently been applied to the assessment of body composition. To evaluate the accuracy of DPA in detecting small changes in the lean soft tissue mass, we performed DPA with the use of the Norland 2600 Dichromatic densitometer on six healthy adult males before and after a 30-ml/kg transfusion of saline and before and after exercise in a warm environment, resulting in a greater than or equal to 1-kg weight loss. Absolute weight [baseline pretransfusion r2 = 0.999, standard error of estimate (SEE) = 590 g; posttransfusion r2 = 0.999, SEE = 300 g; baseline pretranspiration r2 = 0.999, SEE = 230 g; posttranspiration r2 = 0.999, SEE = 240 g] was accurately reflected in DPA total mass. Weight changes due to transfusion were poorly reflected by changes in DPA total mass (r2 = 0.417, SEE = 404 g). However, changes posttranspiration were accurately reflected in the DPA total mass (r2 = 0.886, SEE = 106 g posttranspiration). Similarly, weight changes due to transfusion were poorly measured by changes in DPA soft mass (r2 = 0.478, SEE = 365 g), but changes posttranspiration were highly correlated with DPA soft mass changes (r2 = 0.909, SEE = 92 g). Weight changes were not reflected by changes in the DPA lean soft tissue mass (r2 = 0.006, SEE = 1,737 posttransfusion, r2 = 0.094, SEE = 1,038 g posttranspiration). DPA-derived nonfat mass was highly correlated with skinfold-derived nonfat mass (r2 = 0.96, SEE = 2,400 g). Accuracy of total and soft tissue measurements implied correct mineral mass assessment.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Effects of recombinant murine tumor necrosis factor-alpha on immune function.

TNF-alpha is a macrophage-derived cytokine with diverse biologic activities, including potent immunomodulatory effects. In vitro studies have implied that TNF-alpha has predominantly proinflammatory and immunostimulatory effects, but paradoxically in vivo studies have demonstrated that administration of TNF-alpha suppresses murine lupus. To assess the effects of TNF-alpha on immune function in normal mice, we treated C57BL/6 mice with recombinant murine TNF-alpha (10 micrograms i.p.) or PBS on alternate days for up to 8 wk. Administration of TNF-alpha decreased the percentage of splenic T and B cells and increased the percentage of splenic macrophages without significantly altering the total number of mononuclear cells. Administration of TNF-alpha also caused progressive inhibition of splenic lymphocyte function, out of proportion to the quantitative reduction in B and T cells. After 8 wk of therapy, the proliferative responses of splenic lymphocytes to Con A, PHA, and LPS were reduced by 100, 90, and 60%, respectively, in treated mice compared with control mice. The reduction in T cell proliferation was due primarily to alteration of accessory cell function rather than direct inhibition of T cell function. Treatment with TNF-alpha markedly inhibited T cell cytotoxicity induced by immunization with allogenic target cells, and it virtually ablated NK cell activity. Inhibition of these in vitro tests of lymphocyte function correlated with inhibition of delayed type hypersensitivity in vivo. In contrast, treatment with TNF-alpha did not impair humoral immunity. These findings imply that TNF-alpha may affect cell-mediated immunity more profoundly than humoral immunity. This observation may be relevant to the mechanism whereby TNF-alpha suppresses murine lupus.

Animals

The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications.

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.

Adult

Membrane transport of sodium ions in erythrocytes of the American black bear, Ursus americanus.

1. Membrane transport of Na ions was investigated in red blood cells of bears by methods of measurement of unidirectional isotopic fluxes. 2. Like red blood cells of dogs, bear red cells contain a high Na concentration and low concentrations of K and ATP. 3. As in dog red cells, Na efflux from bear cells was not inhibited by ouabain but was activated by the presence of Ca in the medium, possibly indicating the presence of a Na-Ca exchange mechanism. 4. ATP depletion of cells was accelerated by Ca in the medium, consistent with the presence of a strong ATP-dependent Ca pump. 5. As in other carnivore red cells, Na influx into bear cells was strongly activated by shrinkage and inhibited by swelling. Shrinkage-activated influx was blocked by amiloride. 6. Amiloride-sensitive influx was activated by cytoplasmic Ca and also correlated with the presence of a Na-dependent, amiloride-sensitive H loss. 7. Amiloride-sensitive Na influx exhibited a strong seasonal cycle with a minimum in the middle of the hibernation period, suggesting a possible avenue of cellular energy conservation.

Animals

Vestibulo-ocular reflex as a parameter of seasickness susceptibility.

The vestibulo-ocular reflex (VOR) is known to be modulated in response to changing vestibular and optokinetic stimuli. The purpose of this study was to investigate possible relationships between VOR and future susceptibility and habituation to seasickness. Thirty candidates for future maritime service were exposed to a series of yaw axis smooth harmonic accelerations before and after 6 months of regular sailing, and their VOR gain and phase responses were recorded. Seasickness severity was estimated after 1 and 6 months of service by a questionnaire. We conclude that VOR gain at 0.01 Hz may serve as a physiologic correlate helping to predict seasickness susceptibility, and that the increase in phase lead at 0.02 Hz may mark the habituation process to sea conditions.

Acceleration

Hyperbaric oxygenation for necrotizing (malignant) otitis externa.

Two patients with extensive necrotizing otitis externa have been treated by hyperbaric oxygenation. One patient had facial nerve palsy and the other suffered from skull base involvement. Due to severe side effects, the preferred combined intravenous antibiotic therapy was changed to monotherapy in one case and completely withdrawn in the second. This was done before the commencement of hyperbaric oxygenation, while the necrotizing infection was still active. Hyperbaric oxygenation therapy was followed by complete resolution of the necrotizing otitis externa, which did not recur. The pathogenesis of the disease and mechanisms by which hyperbaric oxygenation might be of benefit are described. We conclude that hyperbaric oxygenation should be considered as adjuvant therapy for necrotizing otitis externa whenever a therapeutic pressure chamber is available.

Aged

Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice.

We studied the effects of recombinant murine tumor necrosis factor-alpha (TNF-alpha) on autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Treatment with TNF-alpha, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-alpha were alive compared with 42% of control mice (P less than 0.05). Administration of TNF-alpha delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the improvement in survival, treatment with TNF-alpha did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-alpha may retard murine lupus in B/W mice through effects on cellular rather than humoral mechanisms. Our findings also indicate that the beneficial effects of TNF-alpha cannot be sustained indefinitely by chronic therapy.

Animals

Does residual insulin secretion (assessed by C-peptide concentration) affect lipid and lipoprotein levels in insulin-dependent diabetes mellitus?

1. Residual endogenous insulin secretion can be assessed by the circulating C-peptide concentration and is present in up to 15% of subjects with established insulin-dependent diabetes mellitus (IDDM). Its role in lipid metabolism in IDDM is not clearly defined. We examined the relationships between serum lipid and lipoprotein concentrations and the response of circulating C-peptide to a test meal in 205 subjects with IDDM. 2. Lipid and lipoprotein levels and glycaemic control did not differ significantly between patients with undetectable, low or high C-peptide responses. 3. High density lipoprotein (HDL) cholesterol and its subfractions were inversely related to concentrations of serum triacylglycerols (P less than 0.01-0.001), but not to C-peptide or glycated haemoglobin (HbA1) levels. Levels of HbA1 and triacylglycerols were correlated with one another (P less than 0.01). Analysis of variance revealed that differences in gender and triacylglycerol concentrations were the most important determinants of HDL and HDL2 cholesterol levels. C-peptide only exerted a weak effect on HDL2 cholesterol levels and no significant predictors of HDL3 cholesterol were found. 4. It is concluded that endogenous insulin secretion (assessed by C-peptide concentration) is relatively unimportant in modifying HDL metabolism in IDDM and that associated clinical features, in particular ambient hypertriglyceridaemia, are of greater importance.

Adolescent

Detection of crystals in synovial fluids by light microscopy: sensitivity and reliability.

Polarised light microscopy of synovial fluid is an established diagnostic technique widely regarded as reliable for the detection of crystals. The threshold concentration of crystals which can be detected has been investigated and the sensitivity and specificity of six observers compared. Various concentrations of laboratory manufactured crystals of monosodium urate monohydrate (MSUM), calcium pyrophosphate dihydrate (CPPD), and basic calcium phosphates (BCP) were added to the synovial fluid. The threshold for reliable identification of MSUM and CPPD was in the range of 10-100 micrograms/ml. False positives were frequent. The mean sensitivity of the six observers for MSUM was 69% and for CPPD was 82%. The mean specificity for MSUM was 97% and for CPPD was 78%. There was much discrepancy in the results of the slides stained with alizarin red S. Thus the value of alizarin red S as a screening test for BCP is questioned. In view of the variable sensitivity and specificity of different observers for MSUM and CPPD and the concentration threshold for reliable crystal identification, greater caution in the interpretation of synovial fluid analysis is advised, and recommendations for increased quality control are supported.

Anthraquinones

The process of recovering from anorexia nervosa.

The authors describe the process of recovering from anorexia nervosa as it is revealed by 13 women who have recovered from the illness. Emphasizing the patient's perspective, the paper reviews the perceived causes of the disorder, helpful and harmful therapy-related and life experiences, features hardest to change, the defensive function of anorexia nervosa and residual traits. Generally, the movement toward health entails forming a therapeutic relationship in which the anorexic can identify and express feelings, experience the empathic, nonjudgmental understanding of another person, separate from a pathological family system, resolve hostile dependent attachment to parents, assuage primitive guilt, and engage in the trials of adolescent psychosexual development to enter adulthood with the beginnings of a firm, cohesive sense of self.

Adult

The parents' relationship and the child's illness in anorexia nervosa.

The authors examine the impact on the preanorexic child of the parents' relationship with one another, particularly the models they present of mature male/female relationships. The authors suggest that patterns of maternal perfectionism and self-sacrifice combined with paternal entitlement makes sexual maturity particularly threatening for female children in these families, and may partially explain the greater incidence of anorexia nervosa in women, and its explosive incidence in adolescence.

Anorexia Nervosa

Prevalence of mitral valve prolapse in primary fibromyalgia: a pilot investigation.

Fifty patients with primary fibromyalgia and a negative cardiovascular symptom history underwent echocardiography to determine the prevalence of mitral valve prolapse (MVP). The mean age of the population was 40 +/- 13 years (14 men, 36 women). Mitral valve prolapse was detected in 75%; 33% with myxomatous mitral valve leaflets. The prevalence of MVP in this population is significantly higher (p less than 0.0001) than in the general population. Primary fibromyalgia and MVP may be part of a more generalized connective tissue abnormality characterized by distinct genetically determined variants.

Adult