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Biomedical subjects

C Gordon

Publications and source records attributed to C Gordon.

At least 127 records · Page 7Linked to original sources
PubMed1996

Undiagnosed systemic lupus erythematosus in the community.

BACKGROUND: Systemic lupus erythematosus (SLE) produces a wide range of symptoms, some of them mild; therefore it may be underdiagnosed. In a pilot study we tested the ability of a screening questionnaire to identify undiagnosed cases in the community. METHODS: A 10-item questionnaire was mailed to 3500 women aged 18-65 randomly selected from a general practice list in Birmingham, UK. A random sample of 300 non-respondents were sent two further mailings. Women returning the questionnaire with three positive answers were to attend for an antinuclear antibody (ANA) test; and those testing positive were to be referred to a rheumatologist for standard clinical assessment. FINDINGS: 1153 (30%) of the women responded, and 307 of these gave three or more positive answers on the questionnaire. The survey disclosed three women with previously undiagnosed SLE; and, in addition, it picked up all four of the women whose SLE had been diagnosed previously. INTERPRETATION: The prevalence of SLE revealed by this survey in Birmingham women is 200/100,000 (95% confidence interval 80 to 412), whereas the prevalence of diagnosed SLE in this age group is 54/100,000 (95% CI 47-62). Thus, a substantial number of undiagnosed cases exist, and further work needs to focus on the prevalence in different ethnic groups and the benefits of early diagnosis and treatment.

Adolescent↗
PubMed1996

Active systemic lupus erythematosus is associated with the recruitment of naive/resting T cells.

The aim of this study was to determine whether active systemic lupus erythematosus (SLE) is associated with recruitment of resting CD45RA+ T cells or reactivation of CD45RO+ memory T cells. Three-colour immunofluorescence was used to determine CD45 isoform expression by CD4+ T cells from 28 patients with SLE. Newly recruited and highly differentiated primed T cells were distinguished by their CD45RB expression. The pattern of CD45 isoform expression varied directly with time since the onset of symptoms in patients with active SLE. Shortly after symptoms appeared, most cells were CD45RA+ resting cells or CD45RO(dull)RB(bright) early primed cells. However, over the course of active disease, patients accumulated CD45RO(bright)RB(dull) cells which represent an advanced state of differentiation. The switch from an early to late primed phenotype correlated significantly with time since the onset of symptoms. The recruitment of resting T cells in active SLE, rather than the simple reactivation of existing memory clones, has implications for understanding the pathology of this disease and for treating it.

Biomarkers↗
PubMed1996

May we support your decision?

Expert systems to support medical decision-making have so far achieved few successes. Current technical developments, however, may overcome some of the limitations. Although there are several theoretical currents in medical artificial intelligence, there are signs of them converging. Meanwhile, decision support systems, which set themselves more modest goals than replicating or improving on clinicians' expertise, have come into routine use in places where an adequate electronic patient record exists. They may also be finding a wider role, assisting in the implementation of clinical practice guidelines. There is, however, still much uncertainty about the kinds of decision support that doctors and other health care professionals are likely to want or accept.

Bayes Theorem↗
PubMed1995

Developmental changes of the 26 S proteasome in abdominal intersegmental muscles of Manduca sexta during programmed cell death.

cDNA clone MS73 codes for an ATPase that is a regulatory subunit of the 26 S proteasome. Reverse transcriptase polymerase chain reaction analysis demonstrates that the expression of the gene dramatically increases in the pre-eclosion period. Western analyses show increases in other related. ATPases including MS73, MSS1, and mts2 but not TBP1. A similar increase in the 30-kDa subunit of the 20 S proteasome occurs. There are accompanying large changes in the peptidase activities of the 26 S proteasome. Relative to the 30-kDa subunit, there is no change in MSS1 and MS73, a 3-fold increase in mts2, and a 5-fold decline in TBP1. A large increase in the concentration of 26 S proteasomes together with extensive regulatory reprogramming may facilitate rapid muscular proteolysis.

Algorithms↗
PubMed1995

The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth.

OBJECTIVE: To establish the point prevalence of systemic lupus erythematosus (SLE) on January 1, 1992, and the incidence of SLE during 1991, in Birmingham, England, a large city with a broad ethnic mix. METHODS: Six sources were used to ascertain patients with diagnosed SLE, including notification by attending and primary care physicians, the lupus patient support group, and hospital inpatient and laboratory data. RESULTS: There were 242 SLE patients (227 females, 15 males) identified: prevalence rate 27.7/100,000 (95% confidence interval 24.2-31.2/100,000) in the population and 206.0/100,000 in Afro-Caribbean females. No significant differences in female ethnic prevalence rates by place of birth were observed. Thirty-three patients developed SLE in 1991: incidence rate 3.8/100,000/year (95% confidence interval 2.5-5.1/100,000/year). CONCLUSION: This study illustrates dramatic differences in incidence and prevalence rates in the UK, depending on ethnic group and irrespective of place of birth.

Adolescent↗
PubMed1995

Choice of treatment affects plasma levels of insulin-like growth factor-binding protein-1 in noninsulin-dependent diabetes mellitus.

Insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) modulates the metabolic and mitogenic effects of IGFs. Although IGFBP-1 levels are abnormally high in insulin-dependent diabetes (IDDM), relatively little is known in NIDDM; conflicting data have suggested both high and low levels. We investigated whether treatment modifies IGFBP-1 levels in two groups of NIDDM patients. Study 1 examined fasting concentrations in groups of patients with NIDDM, comparable except for treatment type (sulfonylurea, n = 23; once daily insulin, n = 15; sulfonylurea plus once daily insulin, n = 14; multiple insulin injections, n = 9) and 25 nondiabetic subjects. In sulfonylurea-treated patients there were markedly reduced plasma IGFBP-1 concentrations (median, interquartile range in parentheses): control, 61.0 (36-96) micrograms/L; sulfonylureas alone, 31.5 (21-61) micrograms/L (P < 0.01); and sulfonylureas plus insulin, 31.5 (9-53) micrograms/L (P < 0.01). Once daily insulin was associated with values similar to those in the control group [62.0 (27-103) micrograms/L; P = NS], whereas IGFBP-1 levels were higher with multiple insulin injection therapy [156.0 (71-184) micrograms/L; P < 0.05]. Proinsulin levels were higher in sulfonylurea-treated patients, but there was no significant correlation between IGFBP-1 and proinsulin within any individual group. Study 2 examined the effects of treatment on the dynamics of IGFBP-1 levels between 0800-1900 h. In control subjects (n = 8), levels fell from 0800 h (mean +/- SEM, 22.4 +/- 5.2 micrograms/L) to 1000 h (14 +/- 5.2 micrograms/L), followed by a rise, more rapid after food, to a peak at 1240 h (20.6 +/- 3.7 micrograms/L). Levels then declined until 1500 h (10.7 +/- 2.9 micrograms/L), with a further postprandial peak at 1840 h (23.1 +/- 3.2 micrograms/L). Sulfonylurea therapy (n = 6) resulted in a complete loss of this pattern, with a marked fall in IGFBP-1 from 0800 h (22 +/- 2.7 micrograms/L) to less than 7 micrograms/L for the remainder of the study (area under the curve, 1150-1400 h, P < 0.001 vs. control). By contrast, in metformin-treated patients (n = 7), neither IGFBP-1 levels nor postprandial peaks were significantly different from those in the control group. Our findings suggest that in patients with NIDDM, the regulation of IGFBP-1 is markedly influenced by the choice of treatment.

Carrier Proteins↗
PubMed1995

Practice guidelines and healthcare telematics: towards an alliance.

This chapter reviews the motives behind the promotion, development and application of practice guidelines, defined as "systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances'. It surveys the state of progress and future prospects for telematics applications in this area, and reports the action points recommended by the 1994 AIM Conference. There exists significant evidence that use of guidelines can improve healthcare process and outcome, and that computerised aids assist this effect, they may also enhance the potential uses of guidelines and protocols for audit, resource management and shared care. A standard generic model for computerised representation of guidelines as knowledge bases in a common format has been proposed and may be a key factor in future progress. The development of computerised patient records of adequate scope and quality is generally recognised as an essential condition for computer-aided guideline use. Support for development, dissemination and application of healthcare guidelines and use has emerged, notably through the AIM EPISTOL study, as a feasible and useful application area of medical knowledge-based systems. It is essential that telematics developments in this field are grounded in an understanding of the healthcare practices to which guidelines are being applied, and of the changes in practice which guideline use may entail.

Artificial Intelligence↗
PubMed1994

Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus.

OBJECTIVE: We have previously described associations between an allele of the interleukin-1 receptor antagonist gene (IL1RN) and several inflammatory diseases. In this study we tested the IL1RN gene as a possible marker in patients with systemic lupus erythematosus (SLE). METHODS: Eighty-one SLE patients and 261 ethnically matched control subjects were genotyped by polymerase chain reaction. RESULTS: We found an increase in both frequency and carriage rate of IL1RN*2 in the SLE group. This association strengthened with extensive disease and particularly with the presence of photosensitivity and discoid skin lesions. CONCLUSION: We describe a novel association between IL1RN*2 and SLE. Carriage of the allele seems to influence severity rather than susceptibility to SLE. We postulate that the association of this polymorphism with disease severity is a widespread feature of common inflammatory and autoimmune diseases.

Base Sequence↗
PubMed1994

A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha.

We have investigated the significance of tumor necrosis factor alpha (TNF-alpha) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA-B, -DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti-Ro and anti-La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA-DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA-B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA-DR3 showed the strongest disease association, we could not demonstrate association of HLA-DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti-Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti-La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA-DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8-DR3 haplotype, TNF-alpha polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.

Autoantibodies↗
PubMed1994

DILEMMA: logic engineering in primary care, shared care and oncology (AIM Project A2005).

The aim of DILEMMA is to provide tools for the development of decision support systems for use in general medical practice, hospital-based cancer care, and shared care of cancer and cardiology patients. In primary care, the project intends to provide aids to clinical performance in prescribing, referral and the use of clinical guidelines. The demonstrator applications involve telematics and knowledge-based methodology, using an approach termed logic engineering which combines logic programming and software lifecycle methods. DILEMMA will demonstrate systems to assist shared care and home care which should help reduce pressure on secondary health resources and, by disseminating best practice knowledge, improve patient care and patient quality of life.

Artificial Intelligence↗
PubMed1994

Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis.

Levels of soluble adhesion molecules have been shown to reflect their cell surface expression in vitro, and thus may provide a useful surrogate marker of surface expression at inflammatory sites. In patients with SLE and vasculitis, serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selection were determined by ELISA during different stages of disease activity. Levels of soluble(s) VCAM-1 correlated with disease activity in patients with SLE, being significantly higher during active compared with inactive disease (P = 0.003), and normalizing with clinical remission. By contrast, in patients with vasculitis, although sVCAM-1 levels were elevated in active disease, they fell but did not normalize in inactive disease, suggesting that treatment may be suppressing the clinical manifestations rather than targeting the underlying pathogenic mechanism. Soluble ICAM-1 and E-Selectin levels did not relfect disease activity in either SLE or vasculitis.

Adolescent↗
PubMed1994

A profile of fibromyalgia in occupational environments.

The effect of the occupational environment on fibromyalgic patients has not been well studied. Individuals (321) from across the United States completed a questionnaire regarding effects of their current and past occupations on their fibromyalgia. Occupations with a high percentage of responders were general office workers (20%), health care providers (14%) and educators (11%). Of the respondents, 8% were unemployed. Activities reported to aggravate the symptoms of fibromyalgia were computer or typing (37%), prolonged sitting (37%), prolonged standing and walking (27%), stress (21%), heavy lifting and bending (19%) and repeated moving and lifting (18%). Activities that did not appear to exacerbate the symptoms of fibromyalgia included walking (19%), variable light sedentary work (15%), teaching (8%), light desk work (6%) and phone work (6%). Patients with fibromyalgia report that they do not tolerate prolonged, repetitive activities, maintaining any one position for sustained periods of time and jobs with high stress. Light sedentary occupations that allow varied tasks and changing positions appear to be tolerated the best.

Female↗
PubMed1994

Impaired glucose tolerance and insulin insensitivity in primary hyperparathyroidism.

OBJECTIVE: A high prevalence of diabetes mellitus has been shown in patients with primary hyperparathyroidism (PHPT). However, it is unclear whether this is related to the metabolic abnormalities in PHPT or to the presence of other risk factors for glucose intolerance in these patients. The aim of our study was to determine whether glucose intolerance and insulin insensitivity occur in subjects with PHPT who do not have other risk factors for diabetes mellitus. DESIGN: Cross-sectional study of glucose metabolism in PHPT patients without other risk factors for diabetes mellitus, compared to age and body mass index (BMI) matched healthy subjects. SUBJECTS: Nineteen non-obese, non-diabetic, normotensive patients with PHPT and 11 age and BMI matched healthy subjects. MEASUREMENTS: The continuous infusion of glucose test was used to assess glucose tolerance. Plasma glucose and insulin were measured during a 1-hour continuous infusion of glucose (5 mg/kg ideal body weight/min); insulin sensitivity and beta-cell function were derived from the glucose and insulin data by mathematical modelling. Fasting serum concentrations of parathyroid hormone, ionized calcium and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured in all subjects. RESULTS: PHPT patients attained higher plasma glucose levels at the end of the glucose infusion (median 9.0 (interquartile range 8.1-9.8) mmol/l) than did controls (7.9 (7.1-8.9) mmol/l, P < 0.05), and 8 (42%) PHPT patients had impaired glucose tolerance. Insulin sensitivity was lower in PHPT (60.3% (49.8-85.4)) than in controls (113.7% (89.3-149.2), P < 0.001); beta-cell function was not different in PHPT subjects. PHPT subjects with impaired glucose tolerance had reduced beta-cell function compared to PHPT subjects with normal glucose tolerance (89.9% (70.5-106.4) vs 120% (98.8-156.6) respectively, P < 0.05). No significant correlations were found between insulin sensitivity and PTH (rs = -0.21), 1,25(OH)2D (rs = -0.14), ionized calcium (rs = -0.11) and inorganic phosphate (rs = 0.34). Beta-cell function did not correlate with PTH (rs = 0.15), 1,25(OH)2D (rs = 0.04), ionized calcium (rs = 0.23) or inorganic phosphate (rs = -0.35). CONCLUSION: Insulin insensitivity is present in PHPT even in the absence of hypertension and obesity, and may be the cause of glucose intolerance and diabetes. PHPT subjects with reduced beta-cell function are more likely to develop glucose intolerance.

Adult↗
PubMed1994

Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D.

Glucose metabolism was studied in a patient with vitamin D deficiency during its treatment with small doses of vitamin D. A continuous infusion of glucose test was performed to assess glucose tolerance and insulin sensitivity and beta-cell function were derived by mathematical modelling. Fasting glucose was 5.6 mmol/l and achieved glucose after the infusion was 10.4 mmol/l confirming diabetes. The test was repeated 0.5, 1, 3 and 5 months after starting treatment. Serum calcium increased glucose intolerance from 1.76 to 2.0, 2.08, 1.96 and 2.0 mmol/l, respectively; vitamin D reached supraphysiological levels initially and returned to normal levels, and parathyroid hormone levels were normalized. Her weight did not change during treatment. Glucose tolerance improved during treatment and achieved glucose was 9.4, 8.6, 9.2 and 9.0 mmol/l at 0.5, 1, 3 and 5 months, respectively; insulin sensitivity did not change. Beta-cell function improved from 101% at diagnosis to 126%, 147%, 173% and 198% at 0.5, 1, 3 and 5 months, respectively. Improvement in beta-cell function and consequently in glucose tolerance is likely to have been due to correction of hypocalcaemia, vitamin D deficiency and secondary hyperparathyroidism.

Aged↗
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↗