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Biomedical subjects

O Dewit

Publications and source records attributed to O Dewit.

At least 19 recordsLinked to original sources

Once daily MMX mesalazine for the treatment of mild-to-moderate ulcerative colitis: a phase II, dose-ranging study.

BACKGROUND: SPD476 (MMX mesalazine), is a novel, once daily, high-strength mesalazine formulation (1.2 g/tablet) that utilizes Multi Matrix System (MMX) technology to delay and extend delivery of the active drug throughout the colon. AIM: To assess the safety and efficacy of MMX mesalazine in patients with mild-to-moderately active ulcerative colitis, in a pilot, phase II, randomized, multicentre, double-blind, parallel-group, dose-ranging study (SPD476-202). METHODS: Thirty-eight patients with mild-to-moderately active ulcerative colitis were randomized to MMX mesalazine 1.2, 2.4 or 4.8 g/day given once daily for 8 weeks. Remission ulcerative colitis-disease activity index (UC-DAI) < or =1, a score of 0 for rectal bleeding and stool frequency, and > or =1 -point reduction in sigmoidoscopy score from baseline was the primary end point. RESULTS: Week 8 remission rates were 0%, 31% and 18% of patients receiving MMX mesalazine 1.2, 2.4 and 4.8 g/day respectively. No statistically significant difference in remission was observed between treatment groups. MMX mesalazine 2.4 and 4.8 g/day groups demonstrated greater improvement in overall UC-DAI and component scores from baseline, compared with the 1.2 g/day group. CONCLUSION: MMX mesalazine given as 2.4 or 4.8 g/day once daily is well tolerated and effective for the treatment of mild-to-moderately active ulcerative colitis.

Adolescent↗

Video capsule endoscopy in small-bowel malignancy: a multicenter Belgian study.

BACKGROUND AND STUDY AIMS: Early diagnosis of small-bowel tumors is crucial for therapy. Video capsule endoscopy has improved the diagnosis of small-bowel diseases, but data concerning the role of this technique in detecting small-bowel malignancy are scarce. The aim of this paper was to review all capsule endoscopy findings at Belgian hospitals, in order to evaluate the diagnostic yield of capsule endoscopy in the field of small-bowel malignancy. PATIENTS AND METHODS: For this retrospective study, the seven Belgian academic hospitals where the device was being used were asked to review the findings obtained by means of video capsule endoscopy, and to collect information about the cases of small-bowel malignancy. RESULTS: In total, 443 capsule endoscopies were performed up to November 2004, and 11 malignant small-bowel processes were detected (2.5%). The most frequent indications for performing capsule endoscopy in those 11 cases were intestinal bleeding of undefined origin or iron-deficiency anemia. The mean number of diagnostic procedures performed before capsule endoscopy was 3.6. The capsule endoscopy results had a diagnostic yield of 1.6% after classical work-up. In 55% of these cases, capsule endoscopy findings had an influence on therapy. CONCLUSIONS: Tumors of the small bowel remain a rare condition. Video capsule endoscopy is able to detect tumors undiagnosed by classical procedures in about 1.6% of cases and has an impact on the therapy in 55% of the tumor cases.

Aged↗

Serological markers in inflammatory bowel diseases.

This chapter is an overview of the literature on serological markers of inflammatory bowel diseases (IBD), focusing on anti-neutrophil cytoplasm autoantibodies (ANCA) and anti- Saccharomyces cerevisiae mannan antibodies (ASCA). The methodology for ANCA and ASCA testing is first introduced. The value of these markers as diagnostic tools is then discussed. Other chapters are devoted to the potential role of ANCA and ASCA in disease monitoring, disease stratification and as subclinical markers in families. Finally reviewed are other antibodies recently tested in clinical trials such as pancreatic antibodies and antibodies directed against bacterial antigens. The role of these antibodies in the pathophysiology of IBD still needs to be assessed. We also need to identify the ASCA immunogen(s) eliciting the antibody response.

Antibodies, Antineutrophil Cytoplasmic↗

Segmental bioelectrical impedance analysis in children aged 8-12 y: 1. The assessment of whole-body composition.

OBJECTIVES: To investigate the potential of segmental bioelectrical impedance analysis (BIA) for estimating whole-body composition in children. DESIGN: Strengths of relationships were determined between indices of impedance or specific resistivities of body segments and reference four-component model (4-CM) assessments of body composition. SUBJECTS: Eighteen boys and 19 girls aged 8-12 y. MEASUREMENTS: Whole-body and segment BIA and anthropometry were used to calculate impedance indices of the whole body and segments and specific resistivities of segments; total body water (TBW), fat-free mass (FFM) and body fat were assessed using the 4-CM. RESULTS: Segmental BIA indices were significantly related to body composition, provided that appropriate comparisons were undertaken for each index: impedance adjusted for unit segment length was better related to TBW and FFM, whereas segment specific resistivity was better related to body fat. Differences between body composition estimates obtained with the 4-CM and predicted using BIA were partly dependent on limb-to-trunk ratios of BIA indices. CONCLUSION: Segmental BIA has potential for providing additional alternative approaches to the assessment of whole-body composition in children: (a) FFM and TBW were best related to impedance adjusted for segment length; (b) body fat was best related to segment specific resistivity; and (c) the relative influences of different segment BIA indices may be utilisable for generating more valid whole-body composition estimates.

Adipose Tissue↗

Segmental bioelectrical impedance analysis in children aged 8-12 y: 2. The assessment of regional body composition and muscle mass.

OBJECTIVES: To investigate the potential of segmental bioelectrical impedance analysis (BIA) for assessing regional composition and muscle mass in children. DESIGN: Strengths of relationships were determined between (a) BIA indices of trunk, limbs or limb segments and (b) segment fat or fat-free mass (FFM) assessed using dual-energy X-ray absorptiometry (DXA); the extent of agreement was established between two independent models, based on DXA and BIA, of limb muscle and adipose tissue (AT) mass. SUBJECTS: Eighteen boys and 19 girls aged 8-12 y. MEASUREMENTS: BIA and anthropometry of trunk, whole limbs, limb segments and defined sections were used to calculate segmental impedance indices and specific resistivities; segment fat and FFM were obtained using DXA; muscle and AT masses of limbs, segments and sections were estimated using DXA and BIA models, and by anthropometry. RESULTS: Segmental BIA indices were significantly related to composition of the segments assessed using DXA; although substantial bias was observed, there was fairly good agreement (low 95% limits of agreement) between the BIA and DXA models of muscle mass and estimates from each were similarly categorised in tertiles, as were estimates of AT. CONCLUSION: Segmental BIA appears to have potential for assessing in children the composition of body segments, as obtained using DXA, and the masses of muscle and AT in whole limbs, limb segments and defined sections.

Absorptiometry, Photon↗

Interaction between azathioprine and aminosalicylates: an in vivo study in patients with Crohn's disease.

BACKGROUND: The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by aminosalicylates has been described in an in vitro study. This could result in a higher risk of bone marrow depression when using the two drugs together. AIM: To investigate the in vivo interaction between azathioprine and aminosalicylates in quiescent Crohn's disease by measuring 6-thioguanine nucleotide levels, thiopurine methyltransferase activity and the plasma levels of the acetylated metabolite of 5-aminosalicylic acid. METHODS: Sixteen patients taking a stable dose of azathioprine, plus sulfasalazine or mesalazine, were enrolled and completed the study. They were not taking any drugs interfering with azathioprine metabolism. Four visits every 4 weeks were held over a 3-month period. Aminosalicylate administration was withdrawn after the second visit. At each visit, the blood cell count, inflammatory parameters, levels of 6-thioguanine nucleotide and the acetylated metabolite of 5-aminosalicylic acid and thiopurine methyltransferase activity were determined. RESULTS: After aminosalicylate withdrawal, mean 6-thioguanine nucleotide levels decreased significantly from 148 pmol (57-357 pmol) to 132 pmol (56-247 pmol) per 8 x 10(8) red blood cells (P=0.027), without significant changes in thiopurine methyltransferase activity or biological parameters. CONCLUSIONS: This in vivo study favours the existence of an interaction between azathioprine and aminosalicylates through a mechanism which remains unclear. This drug-drug interaction should be taken into account when using azathioprine and aminosalicylates simultaneously.

Adult↗

The clinical pharmacokinetics of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate.

BACKGROUND: A new oral pharmacokinetically enhanced formulation of the broad-spectrum antibiotic amoxicillin/clavulanate has been developed to provide more effective therapy against resistant pathogens than is provided by currently available formulations by maintaining therapeutically useful plasma amoxicillin concentrations for a longer period after dosing. OBJECTIVE: This study explored the pharmacokinetics of the new oral formulation of amoxicillin/clavulanate in healthy male and female subjects. METHODS: A single oral dose of pharmacokinetically enhanced amoxicillin/clavulanate (2000/125 mg; 16:1 ratio) was administered to subjects at the start of a meal. After dosing, blood samples were collected at frequent intervals up to 12 hours, and plasma was assayed for amoxicillin and clavulanate concentrations using validated procedures. The new formulation consisted of 1 layer of immediate-release amoxicillin and clavulanate and another of sustained-release amoxicillin in a proportion such that for an amoxicillin minimum inhibitory concentration (MIC) of 4 microg/mL, the time above the MIC (T >MIC) would be approximately > or = 40% over a 12-hour dosing interval. RESULTS: The study enrolled 24 and 31 healthy male and female subjects, respectively. Their mean age was 35 years (range, 18-58 years) and mean body weight was 69 kg (range, 51-86 kg). After the expected sharp peak in plasma amoxicillin concentration, there appeared to be a slower decline with the pharmacokinetically enhanced formulation than is usually seen with conventional formulations, and there was evidence of a second amoxicillin absorption phase. The mean T >MIC for an amoxicillin MIC of 4 microg/mL was 49.4% of a 12-hour dosing interval, a value that cannot be achieved with existing approved doses and formulations of amoxicillin/clavulanate. By 12 hours, plasma amoxicillin concentrations were very low (approximately 0.05 microg/mL), suggesting no expectation of notable dose-to-dose accumulation on repeat dosing with a BID regimen. The terminal half-lives of amoxicillin (1.27 hours) and clavulanate (1.03 hours) with the new formulation were similar to those of existing formulations of amoxicillin/clavulanate. No deaths or serious adverse events were reported. CONCLUSIONS: The enhanced pharmacokinetic profile of amoxicillin/clavulanate seen in this study suggests that this formulation is likely to be highly effective for the oral treatment of infections caused by bacteria--including beta-lactamase-producing organisms--and strains with amoxicillin MICs < or = 4 microg/mL.

Adolescent↗

The potential of near infra-red interactance for predicting body composition in children.

OBJECTIVE: To establish whether near infra-red interactance (NIRI) has potential for use instead of skinfold thickness (SFT) measurements in the assessment of body composition in young children. DESIGN: Strengths of relationships were established between NIRI or SFT measurements and four-component model (4-CM) assessments of body composition. SUBJECTS: Nineteen boys and 19 girls, aged 8-12 y. MEASUREMENTS: 4-CM estimates of body composition were obtained from measurements of body weight, body volume, bone mineral content and total body water. SFT and NIRI were measured at the same four recognized sites (biceps, triceps, subscapular and suprailiac). RESULTS: All children subjectively expressed a preference for NIRI rather than SFT calipers. Although SFTs were slightly more strongly and consistently related to 4-CM estimates, NIRI measurements at the biceps, subscapular and sum of four sites were significantly related to body composition indices. Subscapular NIRI measurements were as successful as subscapular SFTs in ranking subjects relative to 4-CM fatness, both techniques being most successful at lower levels of fatness. CONCLUSION: NIRI has potential for use instead of SFT for estimating body composition in young children. Its contribution may prove to be greatest in sick children in whom SFT measurements may be unwelcome, and weight-for-height indices of little value due to abnormalities of water distribution. However, greater numbers are required to develop child-specific prediction equations and the viability and validity of NIRI in pediatric patients is still to be evaluated.

Adipose Tissue↗

Whole body air displacement plethysmography compared with hydrodensitometry for body composition analysis.

AIMS: To assess the acceptability and feasibility of whole body air displacement plethysmography in children and to determine its precision and agreement with hydrodensitometry, an appropriate reference method. METHODS: Age specific two component model equations were used to predict fat mass from body density in 22 children aged 8-12 years and in 10 adults for comparison of methods. Precision for each method was established from duplicate measurements. RESULTS: Plethysmography was accepted more readily than hydrodensitometry (100% v 69% provided duplicate measurements). Precision for fat mass in children was 0.38 kg by plethysmography and 0.68 kg by hydrodensitometry, and results were similar in adults. The mean (SD) fat mass in children was 6.9 kg (4.0) and 6.7 kg (4. 2) by plethysmography and hydrodensitometry, respectively, but 95% limits of agreement between methods were large (-4.1 kg to 3.5 kg fat). CONCLUSION: Plethysmography was more readily accepted and had better precision than hydrodensitometry. It also provided similar body composition results for the group but not for all individual children.

Adipose Tissue↗

Four-component model of body composition in children: density and hydration of fat-free mass and comparison with simpler models.

BACKGROUND: Body composition in children is generally measured by 2-component (2C) models, which are subject to error arising from variation in fat-free mass (FFM) composition. The 4-component (4C) model, which divides body weight into fat, water, mineral, and protein, can overcome these limitations. OBJECTIVE: The aims of our study were to 1) describe 4C model data for children aged 8-12 y; 2) evaluate interindividual variability in the hydration, bone mineral content, and density of FFM; 3) evaluate the success with which 2C models and bedside techniques measure body composition in this age group with use of the 4C model as a reference. DESIGN: Dual-energy X-ray absorptiometry, underwater weighing, deuterium dilution, bioelectrical impedance analysis, and anthropometry were used to determine body composition in 30 children. The contribution of methodologic error to the observed variability in the hydration and density of FFM was evaluated by using propagation of error. RESULTS: Mean (+/-SD) FFM density and hydration were 1.0864+/-0.0074 kg/L and 75.3+/-2.2%, respectively, and were significantly different from adult values (P < 0.02). Relative to the 4C model, deuterium dilution and dual-energy X-ray absorptiometry showed no mean bias for fatness, whereas underwater weighing underestimated fatness (P < 0.025). Fatness determined by using skinfold-thickness and bioelectrical impedance analysis measurements along with published equations showed poor agreement with 4C model data. CONCLUSIONS: Biological variability and methodologic error contribute equally to the variability of FFM composition. Our findings have major implications for bedside prediction methods used for children, traditionally developed in relation to underwater weighing.

Adipose Tissue↗

Sources of error in bioimpedance spectroscopy.

Two different makes of bioimpedance spectrometer (UniQuest-SEAC SFB-3 and Xitron 4000B) were used for a series of measurements on volunteers and patients in intensive care. Although each machine was accurate over the frequency range 5 to 500 kHz when bench tested on model resistor-capacitor circuits, significant differences in their recorded impedance parameters appeared when used in vivo, especially on intensive care patients. A series of laboratory tests was performed on each machine simulating the situation in vivo to identify possible reasons for these differences. Whilst stray capacitance in the environment was identified as the major contributor to variability in high-frequency performance, interaction between electrode impedance and lead positioning was also a factor. The observed phase shift with frequency or time delay (Td) used in the Xitron modeling software appears to be the result of a time constant caused by stray capacitance and so is unlikely to have any biological meaning. Significant differences in the in vivo numerical values produced by bioimpedance spectrometers may be attributed to instrument design, data processing and, in particular, the clinical environment.

Adult↗

Multiple frequency bioimpedance: a bed-side technique for assessment of fluid shift patterns in a patient with severe dehydration.

This report describes the use of multiple frequency bioimpedance analysis (MFBIA) to monitor fluid changes in a patient who developed severe dehydration and recovered. Initially, the patient weighed 53.2 kg, his total body water (TBW; D(2)0 dilution) was 33.5 L, his extracellular water (ECW; Br dilution) was 19.5 L, and hydration of the fat-free mass (FFM; dual-energy X-ray absorptiometry) was normal (73%). The resistances at infinite and 0 frequency were R(inf) = 454 and R(0) = 580 ohm respectively, which predicted TBW = 33.1 L and ECW = 16.6 L. On day 7, when the weight loss was 7.2 kg, FFM had decreased by 7.4 kg, and R(inf) and R(0) had increased to 662 and 902 ohm respectively, predicting decreases of 5.8 L in TBW and 3.7 L in ECW. On recovery (day 14), all parameters had returned to baseline values. This study encourages the use of MFBIA as a bed-side technique for the serial assessment of body water compartments in patients with disturbances in fluid balance.

Journal Article↗

Plasma leptin, energy intake and hunger following total hip replacement surgery.

1. This study aimed to investigate the possible role of leptin in post-traumatic anorexia by making pre- and post-operative (0-8 days) measurements of circulating leptin concentrations in six patients undergoing elective total hip replacement for osteoarthritis. 2. Mean daily hunger rating (four categories) and food intake (assessed by food record charts) were measured pre-operatively, as well as post-operatively for the first 5 days (days 0-5). Leptin concentrations, circulating metabolites [glucose, non-esterified fatty acids, glutamine and 3-hydroxybutyrate] and insulin and cortisol concentrations were measured pre-operatively (day 0) and post-operatively (days 1, 2, 3, 5 and 8). 3. Mean leptin concentrations were significantly increased only on day 1 (56% increase compared with pre-operative values, P < 0.009), whereas food intake (only 0.6 MJ on day 0) and hunger (5/6 patients 'not hungry' on day 0) only gradually improved over the next few days. (The energy intake over the first 5 days was 56% of the pre-operative value.) 4. Circulating insulin and cortisol concentrations were elevated on day 1 compared with pre-operative values on day 0 (P < 0.05). Of the measured metabolites implicated in the control of food intake, circulating non-esterified fatty acids and 3-hydroxybutyrate were not significantly altered in the post-operative period, but significant hyperglycaemia was noted on day 1 compared with day 0 pre-operatively (8.8 compared with 6.4 mmol/l glucose; P < 0.01). 5. It is concluded that circulating leptin is involved in the early (< 24 h) acute-phase response after moderately severe surgical trauma (characterized biochemically by a substantial acute-phase protein response, hypoalbuminaemia, hyperglycaemia and hypoglutaminaemia). Therefore, leptin may be implicated in post-traumatic anorexia, although other factors are likely to be involved, especially after the first 24 h when circulating leptin concentrations are no longer elevated.

Acute-Phase Reaction↗

Starch digestion in young children with cystic fibrosis measured using a 13C breath test.

The study was designed to evaluate a non-invasive breath test using naturally 13C-rich corn (maize) as substrate to provide quantitative information about the digestion of starch by children in health and disease. The variability of background 13C:12C of young British children was investigated by collecting breath samples over 6 h from 17 healthy children, 6-35 mo old, and from seven children with cystic fibrosis, 25-48 mo old, in their homes. Background 13C enrichment was -26.6 and -25.4 delta per mil in the healthy and cystic fibrosis groups, respectively (p less than 0.01), and varied little during the day (SD = 0.4 delta per mil). Eight healthy children and five with cystic fibrosis were given a test breakfast of corn starch cooked in milk with sugar. The cystic fibrosis group repeated the test with the addition of an enzyme supplement containing alpha-amylase. Subjects accepted variable amounts of starch (range 0.2-2.8 g/kg body wt). The percentage of ingested 13C recovered during the 6 h after the meal increased with age in the healthy children (range 15-53%). Three children with cystic fibrosis had negligible 13C recoveries, and the other two had lower recoveries than expected for their age. The addition of enzymes did not consistently improve 13C recovery. We conclude that the 13C breath test based on corn has potential for investigating starch digestion in young children. Initial results suggest that starch digestion is impaired in some children with cystic fibrosis and that enzyme supplements do not improve digestion consistently or completely.

Breath Tests↗

Prevalence and treatment of giardiasis in chronic diarrhoea and malnutrition.

To determine the prevalence of giardiasis in Gambian children with chronic diarrhoea and to assess their response to treatment, 31 children with chronic diarrhoea and malnutrition were investigated for giardiasis using a combination of serology (specific antigiardia IgM antibody) and microscopy of faeces and jejunal biopsy specimens. Fourteen of 31 children with chronic diarrhoea had giardiasis compared with only four of 33 healthy age and sex matched control children. Four of 15 malnourished children without diarrhoea were giardia positive. Twenty-three children with chronic diarrhoea were reinvestigated after treatment with metronidazole; giardia was found in 11 of them. These results show that giardia is highly prevalent in children with chronic diarrhoea and malnutrition and that the infection does not respond to standard therapeutic measures.

Animals↗

Breast-milk amylase activity in English and Gambian mothers: effects of prolonged lactation, maternal parity, and individual variations.

Breast milk contains an amylase that may contribute to carbohydrate digestion in infants. The aim of our study was to determine whether mothers differ in their breast-milk amylase activity and whether the activity is maintained during prolonged lactation. This was investigated by measuring breast-milk amylase activity by hydrolysis of maltotetraose in 63 English mothers of parity 1-5 and 107 Gambian mothers of parity 1-12 who were at various stages of lactation (0.5-27 mo). Amylase was present in all samples and showed a great range of activity from 0.08 to 3.53 IU/mL. Amylase activities did not vary during a feed nor over 24 h, and each mother had a characteristic level of activity in her milk. Amylase activity was higher in the 1st trimester of lactation, and decreased by 35% (p less than 0.001) to a plateau at 6-27 mo. Gambian mothers of very high parity (parity 11-12) had 54% of the activity of primiparous mothers (p less than 0.001), after adjustment for stage of lactation. Using community data on milk volume, the estimated breast-milk amylase intake by breast-fed children was on the order of 800-1000 IU/24 h in the 1st trimester and 400 IU/24 h in the 2nd year of lactation. Individual measurements emphasized the great differences in this intake among children of the same age. Our study showed that breast milk is an important source of amylase both in developed and developing countries, but there are large variations in intake among children.

Adult↗

Viable starter culture, beta-galactosidase activity, and lactose in duodenum after yogurt ingestion in lactase-deficient humans.

Ten lactose malabsorbers were intubated and given fresh or heated yogurt to which polyethylene-glycol (PEG) and spores of Bacillus stearothermophilus (SBS) had been added as internal standards. In duodenal samples taken after fresh yogurt ingestion, viable starter culture was detected for 60 min in 6 of 7 subjects and the ratio of microbial beta-galactosidase activity to SBS remained similar during this period to its value in the preingested yogurt. In the two groups ingesting fresh and heated yogurt respectively, ratios of lactose to PEG remained similar to preingested values for 90 min and duodenal pH remained less than 5.1. In vitro, at pH 5.0, beta-galactosidase activity in yogurt dropped by 80%. These data clearly show that after fresh yogurt ingestion, viable starter culture reaches the duodenum and contains beta-galactosidase activity. However, the buffering capacity of the yogurt that protects bacteria from acidic gastric secretion also prevents microbial beta-galactosidase from hydrolyzing lactose in the duodenum.

Adult↗