Two cases of 'Wegener's tuberculosis'.
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Aged↗
Biomedical subjects
C Gordon
Publications and source records attributed to C Gordon.
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↗
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↗
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↗
Cytokines and the acute phase response in SLE.
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Acute-Phase Reaction↗
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↗
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↗
Hexosaminidase contamination in bovine serum albumin: a potential problem in screening for gene carriers of Tay-Sachs disease.
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Genetic Carrier Screening↗
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↗
Survival assays with a boronated porphyrin as measured with hamster V-79 cells in culture.
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Animals↗