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Biomedical subjects

G Wild

Publications and source records attributed to G Wild.

At least 55 records · Page 3Linked to original sources

Budesonide in the management of patients with Crohn's disease.

Modern medical therapy is increasingly based on evidence. The evidence presented here is that budesonide (Entocort, Astra Pharma) 9 mg/day is superior to placebo and equivalent to systemically active glucocorticosteroids in achieving disease remission in patients with active Crohn's disease, and in prolonging the recurrence time of symptomatic disease. Budesonide causes less disturbance to adrenal function than prednisone or prednisolone and may cause fewer steroid-associated symptoms. Thus, budesonide is the safer, more effective steroid of choice to treat patients with Crohn's disease.

Anti-Inflammatory Agents↗

Small bowel review: Part II.

Significant advances have been made in the study of the small bowel. Part II of this two-part review of the small bowel examines the early development and later ageing of the small bowel; the effect of diabetes, alcohol, radiation and HIV on the small bowel; enteral and parenteral nutrition; the brush border membrane and enterocyte proliferation; and peptide hormones (including transforming growth factors, motilin peptide YY and cholecystokinin).

Aging↗

Serum IgD levels in children under investigation for and with defined immunodeficiency.

BACKGROUND: The function and regulation of circulating IgD are unclear. Serum IgD levels were increased in a wide range of immunological diseases but these associations did not give a clue to the regulation of serum IgD production. METHODS: Serum IgD levels in 131 children with various non-HIV-related immunodeficiency diseases were investigated to examine their relationship with immunoglobulin or antibody production and activation of the immune system. Data from a group of 109 nonimmunodeficient children were also available for comparison. RESULTS: There was a bimodal distribution of serum IgD levels. In 87 patients IgD levels fell below the limit of detection of 5 IU/ml, while the remainder showed an approximately normal distribution skewed to the right after log transformation. The proportion of children with undetectable IgD levels (< 5 IU/ml) was significantly increased in immunodeficient children (87/131 vs. 28/109, p < 0.001). No difference in the occurrence of immunoglobulin or antibody deficiencies was demonstrated in immunodeficient children with detectable and nondetectable IgD levels. There was a positive correlation of serum IgD with age, serum IgA and IgE, white blood count and CD4+CD25+ lymphocytes but not with other immunoglobulin isotypes or immune activation markers. CONCLUSION: Determination of serum IgD levels did not seem to be of particular clinical benefit in the investigation of HIV-negative immunodeficient children and serum IgD levels were not associated with the general picture of immune activation. Observed distribution patterns and associations may have implications for the regulation of serum IgD production.

Age Factors↗

Cytokines and the malnutrition of chronic renal failure.

Malnutrition in uremic patients remains one of the major causes of morbidity and mortality. Its mediators remain largely unknown. Uremia is characterized by changes in circulating levels of catabolic cytokines and anabolic growth factors. The aim of this study was to investigate whether these changes are associated with the malnutrition of patients with chronic renal failure (CRF). We have studied the prevalence of malnutrition in a small group of patients (n = 20) with CRF (serum creatinine = 551 +/- 105 mumol/l, mean +/- SD) and 25 age-matched controls. Nutritional status was assessed by dietary diaries, subjective global assessment (SGA), and by measurement of anthropometric parameters. Regression analysis was applied to examine the relationship between biochemical and anthropometric parameters. Simultaneously, we have investigated changes in the circulating levels of catabolic cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6] and an anabolic growth factor [insulin-like growth factor-I (IGF-I)]. We observed a high prevalence of malnutrition as judged initially by SGA: 50% moderately malnourished and 15% severely malnourished. This was confirmed by anthropometric measurements. We noted a significant reduction in both triceps skinfold thickness (TST; 35% of patients < 25th centile) and midarm muscle circumference (MAMC, 65% of patients < 25th centile). We also noted a reduction in serum IGF-I in malnourished patients (IGF-I in well-nourished patients = 207 +/- 48 micrograms/l, in malnourished patients = 133 +/- 33 micrograms/l, p < 0.01). IGF-I correlated with TST (r = 0.71, p < 0.001) and MAMC (r = 0.47, p < 0.05). IGF-I had a high predictive value for TST (R2 = 51%, p < 0.001). In contrast, TNF-alpha levels were higher in malnourished patients: 19.5 +/- 30 pg/ml compared to 3.9 +/- 8 pg/ml in healthy patients (p < 0.001) and TNF-alpha showed a negative correlation with MAMC (r = -0.69, p < 0.01; R2 = 47%, p < 0.01). IL-1 beta levels were higher in CRF than in controls but did not correlate with nutritional parameters. No significant changes could be detected in serum IL-6. A significant percentage of predialysis patients with CRF suffer from some degree of malnutrition. This may be attributed in part to a fall in circulating anabolic growth factors and an increase in catabolic cytokines.

Adult↗

Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators.

BACKGROUND: Although corticosteroids are highly effective in improving symptoms of Crohn's disease, they may have substantial toxicity. In some patients, attempts to discontinue corticosteroids are unsuccessful. METHODS: We conducted a double-blind, placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn's disease despite a minimum of three months of prednisone therapy. Patients were randomly assigned to treatment with intramuscular methotrexate (25 mg once weekly) or placebo for 16 weeks. The patients also received prednisone (20 mg once a day), which was tapered over 10 weeks unless their condition worsened. The primary outcome measure was clinical remission at the end of the 16-week trial. Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn's Disease Activity Index. RESULTS: A total of 141 patients were randomly assigned in a 2:1 ratio to methotrexate (94 patients) or placebo (47 patients). After 16 weeks, 37 patients (39.4 percent) were in clinical remission in the methotrexate group, as compared with 9 patients (19.1 percent) in the placebo group (P = 0.025; relative risk, 1.95; 95 percent confidence interval, 1.09 to 3.48). The patients in the methotrexate group received less prednisone overall than those in the placebo group (P = 0.026). The mean (+/- SE) score on the Crohn's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group (162 +/- 12) than in the placebo group (204 +/- 17, P = 0.002). The changes in quality-of-life scores and serum orosomucoid concentrations were similar. In the methotrexate group, 16 patients (17 percent) withdrew from treatment because of adverse events (including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6), as compared with 1 patient (2 percent) in the placebo group. CONCLUSIONS: In a group of patients with chronically active Crohn's disease, methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone.

Adult↗

Nutritional profile of continuous ambulatory peritoneal dialysis patients.

Undernutrition in dialysis patients contributes to their morbidity and mortality. This is a cross-sectional study of the nutritional status of 61 patients treated with continuous ambulatory peritoneal dialysis (CAPD). They were studied with emphasis on assessment of their nutritional intake, anthropometric measurements, and evaluation of biochemical parameters. The correlation between the rate of CAPD peritonitis and these measurements was also examined. The majority of the patients (63.1%) had inadequate protein intake ( < or = 1.2 g/kg/day). A comparable percentage had a low energy intake ( < or = 30 kcal/kg/day). Moderate malnutrition, as assessed by a low triceps skinfold thickness (TST) or a reduced midarm muscle circumference (MAMC) of < or = 20th percentile, was detected in 52% and 39% of the patients, respectively. Severe malnutrition (TST or MAMC < or = 10th percentile) was present in 36% of the patients. The serum insulin-like growth factor I (IGF-I) proved to be the most useful biochemical marker of malnutrition. It showed a positive correlation with TST (r = 0.325; p < 0.05). No significant correlation was observed with other short-life proteins such a transferrin or prealbumin. However, stepwise regression analysis showed the predictive value of serum IGF-I for anthropometric values to be low (adjusted R2 = 34.6%). Wasted patients did not appear to have more infections when compared to their healthier counterparts. However, a weak correlation was observed between TST and the number of peritonitis episodes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anthropometry↗

Traffic through the Golgi apparatus as studied by radioautography.

The ability to radiolabel biological molecules, in conjunction with radioautographic or cell fractionation techniques, has brought about a revolution in our knowledge of dynamic cellular processes. This has been particularly true since the 1940's, when isotopes such as 35S and 14C became available, since these isotopes could be incorporated into a great variety of biologically important compounds. The first dynamic evidence for Golgi apparatus involvement in biosynthesis came from light microscope radioautographic studies by Jennings and Florey in the 1950's, in which label was localized to the supranuclear Golgi region of goblet cells soon after injection of 35S-sulfate. When the low energy isotope tritium became available, and when radioautography could be extended to the electron microscope level, a great improvement in spatial resolution was achieved. Studies using 3H-amino acids revealed that proteins were synthesized in the rough endoplasmic reticulum, migrated to the Golgi apparatus, and thence to secretion granules, lysosomes, or the plasma membrane. The work of Neutra and Leblond in the 1960's using 3H-glucose provided dramatic evidence that the Golgi apparatus was involved in glycosylation. Work with 3H-mannose (a core sugar in N-linked side chains), showed that this sugar was incorporated into glycoproteins in the rough endoplasmic reticulum, providing the first radioautographic evidence that glycosylation of proteins did not occur solely in the Golgi apparatus. Studies with the tritiated precursors of fucose, galactose, and sialic acid, on the other hand, showed that these terminal sugars are mainly added in the Golgi apparatus. With its limited spatial resolution, radioautography cannot discriminate between label in adjacent Golgi saccules. Nonetheless, in some cell types, radioautographic evidence (along with cytochemical and cell fractionation data) has indicated that the Golgi is subcompartmentalized in terms of glycosylation, with galactose and sialic acid being added to glycoproteins only within the trans-Golgi compartment. In the last ten years, radioautographic tracing of radioiodinated plasma membrane molecules has indicated a substantial recycling of such molecules to the Golgi apparatus.

Animals↗

Inter-relationships between platelet count, platelet IgG, serum IgG, immune complexes and severity of liver disease.

Thrombocytopenia is a common finding in subjects with chronic liver diseases. A variety of mechanisms may underlie this. Immunological disturbances are commonly a feature in chronic liver disease, including hyperglobulinaemia and the presence of autoantibodies and circulating immune complexes and immune mechanisms could therefore contribute to thrombocytopenia. We have investigated the relationships between blood platelet count, serum IgG and IgG immune complexes and IgG associated with platelets in 92 subjects with chronic liver disease (27 with chronic active hepatitis, 38 with primary biliary cirrhosis and 27 with alcoholic liver disease). Severity of liver impairment was a major determinant of degree of thrombocytopenia. Also, an inverse relationship was demonstrated between platelet count and platelet-associated IgG. In subjects with chronic active hepatitis the relationships between platelet count, serum IgG immune complexes and platelet-associated IgG were consistent with a role for immune mechanisms in general and immune complexes in particular as mediators of the thrombocytopenia.

Antigen-Antibody Complex↗

Problems of mediator measurement for a national advisory service to U.K. anaesthetists.

Large numbers of life threatening anaphylactoid reactions are encountered following administration of general anaesthesia. Advice on the future management of the survivors is essential and requires investigation of the reaction mechanism. Demonstration of histamine release is important but unlikely to be achieved in life threatening situations. A national advisory service to anaesthetists assesses IgE-mediated histamine release in terms of the presence and utilization of specific antibodies, and non-specific histamine release in terms of urinary methylhistamine excretion.

Anaphylaxis↗

IGF-I, a marker of undernutrition in hemodialysis patients.

Early detection and treatment of malnutrition in patients on hemodialysis (HD) is hampered by lack of a sensitive biochemical marker. We compared the value of serum insulin-like growth factor-I (IGF-I) with other biochemical indices in detecting malnutrition in 61 HD patients. Protein and energy intakes were low in the majority of patients. Of all patients, 59.6% had severe reduction in triceps skinfold thickness (TSF thickness, less than or equal to 60% of normal), whereas midarm muscle circumference (MAMC) was mildly reduced (less than or equal to 90%) in 23%. Serum IGF-I proved superior to the other indices in predicting TSF thickness. A serum IGF-I concentration of 300 micrograms/L discriminated between wasted (TSF thickness less than or equal to 60%) and robust patients. In 16 patients with a history of recent infection, IGF-I was significantly reduced well before changes in anthropometric measurements could be detected. IGF-I is a useful and early marker of undernutrition in HD patients.

Adolescent↗

C4a anaphylatoxin levels as an indicator of disease activity in systemic lupus erythematosus.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in systemic lupus erythematosus (SLE). Elevation of C3a anaphylatoxins was found in two out of 24 patients and elevation of C4a anaphylatoxins was found in 20 out of 24 patients, confirming that complement activation, predominantly by the classical pathway, is a common occurrence in the disease. Significantly higher levels of C4a anaphylatoxin were found in 16 patients, with more aggressive disease requiring supplementary treatment with azathioprine, while the remaining eight patients, with less severe disease, required purely steroid therapy. Very strong associations between elevated C4a anaphylatoxins and raised DNA antibody titres, C1q binding activity and low complement C4 levels were also observed, suggesting that anaphylatoxin measurement may be a sensitive additional method for monitoring disease activity in SLE.

Adult↗

Complement activation in systemic sclerosis.

The use of a synthetic protease inhibitor, nafamstat mesilate, has enabled reliable estimations of in vivo complement activation to be made in patients with systemic sclerosis. Elevations of C3a and C4a anaphylatoxins were found in 2 and 24 out of 30 patients respectively, indicating that complement activation, predominantly by the classical pathway, is a common occurrence in the disease, even though complement C3 and C4 levels were within the reference range.

Adult↗

Carbohydrate deficient transferrin: a marker for alcohol abuse.

OBJECTIVE: To assess the value of serum carbohydrate deficient transferrin as detected by isoelectric focusing on agarose as an indicator of alcohol abuse. DESIGN: Coded analysis of serum samples taken from patients with carefully defined alcohol intake both with and without liver disease. Comparison of carbohydrate deficient transferrin with standard laboratory tests for alcohol abuse. SETTING: A teaching hospital unit with an interest in general medicine and liver disease. PATIENTS: 22 "Self confessed" alcoholics admitting to a daily alcohol intake of at least 80 g for a minimum of three weeks; 15 of the 22 self confessed alcoholics admitted to hospital for alcohol withdrawal; 68 patients with alcoholic liver disease confirmed by biopsy attending outpatient clinics and claiming to be drinking less than 50 g alcohol daily; 47 patients with non-alcoholic liver disorders confirmed by biopsy; and 38 patients with disorders other than of the liver and no evidence of excessive alcohol consumption. INTERVENTION: Serial studies performed on the 15 patients undergoing alcohol withdrawal in hospital. MAIN OUTCOME measure--Determination of relative value of techniques for detecting alcohol abuse. RESULTS: Carbohydrate deficient transferrin was detected in 19 of the 22 (86%) self confessed alcohol abusers, none of the 47 patients with non-alcoholic liver disease, and one of the 38 (3%) controls. Withdrawal of alcohol led to the disappearance of carbohydrate deficient transferrin at a variable rate, though in some subjects it remained detectable for up to 15 days. Carbohydrate deficient transferrin was considerably superior to the currently available conventional markers for alcohol abuse. CONCLUSION: As the technique is fairly simple, sensitive, and inexpensive we suggest that it may be valuable in detecting alcohol abuse.

Alcoholism↗