Profound hypoglycaemia induced by propranolol in a patient with hepatic cirrhosis and severe hyperandrogenaemia.
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Adult↗
Biomedical subjects
C Gordon
Publications and source records attributed to C Gordon.
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗