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G A Meijer

Publications and source records attributed to G A Meijer.

At least 19 recordsLinked to original sources

Quantification of proliferative activity in colorectal adenomas by mitotic counts: relationship to degree of dysplasia and histological type.

AIM: Proliferative activity of tumours reflects their malignant potential. In colorectal adenomas, a subjective impression of the number of mitoses is a criterion often used to assess the degree of dysplasia. Since these subjective impressions of mitotic activity may lack reproducibility, the aim of this study was to perform an objective analysis. METHODS: Mitotic counts were conducted in tissue sections of 59 colorectal adenomas. Of these, 20 showed mild, 20 moderate, and 19 severe dysplasia, according to blind duplicate assessments by two pathologists. Forty three were classified as tubular adenomas and 16 as "villous" adenomas (tubulo-villous and villous). The number of mitoses, both per unit area of epithelium (area weighted mitotic counts, AWMC) and per colonic crypt (mitotic counts per colonic crypt MCCC), was scored in the most dysplastic area within the adenoma. Mitotic figures were counted using a light microscope (ocular x 10, objective x 40, NA 0.75), and the area of the glandular epithelium was measured using an interactive video overlay measurement system. Twenty glands per specimen were assessed. In the intra-observer reproducibility tests, the coefficients of error for the AWMC and MCCC were 4.5% and 7.4% respectively. RESULTS: For the AWMC a significant difference was found between mild and moderate as well as between mild and severe dysplasia, but not between moderate and severe dysplasia. The results of the MCCC showed the same trend, but the differences did not reach a significant level. Furthermore, cases classified as mild dysplasia were found that showed numerous mitoses, while cases classified as severe dysplasia were found with only very few mitoses. No significant difference in AWMC was found between tubular and villous adenomas. Thus the different malignant potential of tubular and villous adenomas was not reflected by a difference in AWMC. A seemingly strong difference for MCCC between tubular and "villous" adenomas appeared to depend completely on the difference in crypt size between these two groups. CONCLUSIONS: The area weighted mitotic count, rather than the mitotic count per colonic crypt, may be useful for assessing the proliferation rate in colorectal adenomas.

Adenoma, Villous

Free amino acids in plasma and muscle of high yielding dairy cows in early lactation.

Free AA in plasma and muscle were monitored in 36 dairy cows from 2 wk before until 15 wk after parturition. Cows were kept indoors and fed individually. The AA concentrations in plasma from 6 to 15 wk of lactation were compared with precalving concentrations. Plasma concentrations of Met, Phe, Glu, and Gln decreased by 16, 24, 25, and 25%, respectively. The ranking of the essential AA according to their decrease in plasma corresponded to the order in which they generally appear to be limiting for milk protein synthesis. The decrease of Glu and Gln in plasma exceeded that of the essential AA and contrasted strongly with all other nonessential AA. The change in the AA profile in muscle from pregnancy to lactation resembled that described for the catabolic state in mammals and suggests that muscle protein was degraded for supply of AA to the udder, despite excess protein and energy supply 15 wk into lactation. In muscle, the decrease in the pool of free Gln exceeds 25% and is higher than for any other AA. These observations support our hypothesis that Gln is potentially limiting for milk protein synthesis in the high yielding dairy cow.

Amino Acids

Body mass, body composition and sleeping metabolic rate before, during and after endurance training.

Metabolic rate, more specifically resting metabolic rate (RMR) or sleeping metabolic rate (SMR), of an adult subject is usually expressed as a function of the fat-free mass (FFM). Chronic exercise is thought to increase FFM and thus to increase RMR and SMR. We determined body mass (BM), body composition, and SMR before, during, and after an endurance training programme without interfering with energy intake. The subjects were 11 women and 12 men, aged 37 (SD 3) years and body mass index 22.3 (SD 1.5) kg.m-2. The endurance training prepared subjects to run a half marathon competition after 44 weeks. The SMR was measured overnight in a respiration chamber. Body composition was measured by hydrostatic weighing. Measurements were performed at 0, 8, 20, 40, and 90 weeks after the start of the training. The BM had decreased from a mean value of 66.6 (SD 6.9) to 65.6 (SD 6.7) kg (P < 0.01), fat mass (FM) had decreased from 17.1 (SD 3.9) to 13.5 (SD 3.6) kg (P < 0.001), and FFM had increased from 49.5 (SD 7.3) to 52.2 (SD 7.6) kg (P < 0.001) at 40 weeks. Mean SMR before and after 40 weeks training was 6.5 (SD 0.7) and 6.2 (SD 0.6) MJ.day-1 (P < 0.05). The decrease in SMR was related to the decrease in BM (r = 0.62, P = 0.001). At 90 weeks, when most subjects had not trained for nearly a year, BM and SMR were not significantly different from the initial value while FM and FFM had not changed since week 40 of training.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Stereological assessment of architectural changes in dysplastic epithelium of colorectal adenomas.

BACKGROUND: Against the background of developing quantitative prognostic indicators for the future risk of colorectal cancer in adenoma bearing-patients, the possibilities of stereological measuring techniques for providing objective measures of architectural changes in colorectal adenomas were examined. MATERIAL AND METHODS: The haematoxylin-eosin stained tissue sections of 59 adenomas, of which 20 showed mild dysplasia, 20 moderate dysplasis, and 19 severe dysplasia, were assessed. Using a projection microscope equipped with a coherent test system that was specifically designed to analyze anisotropic tissue, the volume density of stroma, epithelium and lumen, the outer and the inner gland surface density, and the length density lumen were determined. RESULTS: With respect to grading, significant differences in the means of the inner gland surface density and the length density lumen were found mainly between mild and severe dysplasia as well as between moderate and severe dysplasia. This was especially evident when considering the subgroup of tubular adenomas. Stepwise discriminant analysis resulted in an overall correct jackknifed classification of 81.3% when mild and moderate dysplasia cases were taken as one group, and were compared with the group of severe dysplasia cases. With respect to histological type, the volume density lumen and the outer surface density glands, were most favourable. These two features allowed for an 87.5% overall correct jackknifed classification of tubular adenomas, versus adenomas with villous components. The analysis time was roughly 30 minutes per polyp. Intra-observer reproducibility was satisfying, with CE-values < or = 5% for all variables. Inter-observer reproducibility tests were encouraging. CONCLUSIONS: The application of stereological techniques can be worthwhile in assisting in the classification of colorectal adenomatous polyps. Such techniques could therefore be a useful tool to estimate the prognostic value of adenoma morphology with respect to the development of metachronous colorectal tumours.

Adenomatous Polyps

Physical activity and energy expenditure in lean and obese adult human subjects.

We compared the physical activity of 11 lean and 11 obese men and women over a 7-day period. There were no significant differences in either the amount of movement recorded with an accelerometer (9.5 (SD 3.9) vs 9.9 (SD 2.6) kcounts.day-1), or in the energy expenditure due to physical activity reflected by the difference between the average daily metabolic rate measured by the doubly labelled water technique and the sleeping metabolic rate measured in a respiration chamber and adjusted for fat-free mass: 112 (SD 33) vs 118 (SD 22) kJ.kg-1.day-1. The obese showed a non-significant loss of body mass of 0.5 (SD 1.1) kg, probably due to reduced intake during the 7-day intake recording period.

Adult

Cytonuclear morphometry in the assessment of dysplasia in colorectal adenomatous polyps. A pilot study.

In order to objectify the degree of dysplasia, results of nuclear and cellular morphometry were compared with assessed grades of dysplasia in 32 colorectal adenomatous polyps. Of these adenomas 8 showed mild, 17 moderate and 7 severe dysplasia (according to blind duplicate assessments by two pathologists). Using a microscope video-overlay interactive digitizing measurement system, 100 nuclei were measured in each specimen according to a strict measurement protocol. In a stepwise discriminant analysis the best discriminating features appeared to be mean stratification index, N/C ratio, mean contour ratio and mean form AR. Overall with these features 65.6% correct jackknifed classification of the 32 cases could be achieved. On the other hand, a clear three-group distinction could not be obtained, even with the best set of discriminating features. Similarly to gastric dysplasia, the morphometric features might be used to design a two-grade (low, high) rather than a three-grade system to assess the degree of dysplasia. These findings make clear that objectifying the degree of dysplasia in adenomatous polyps is possible by means of interactive morphometric analysis.

Adenoma

Fat-free mass as a function of fat mass and habitual activity level.

The best predictor of energy expenditure in man is the fat-free mass of the body. Fat-free mass explains most of the variation in resting metabolic rate and even in total metabolic rate under sedentary conditions. We studied possible determinants of fat-free mass as routes to influence energy metabolism. Existing data sets were analysed with observations on height, fat mass (FM), fat-free mass (FFM), and habitual level of physical activity (PA). PA was calculated from average daily metabolic rate (ADMR) as measured over 1-4-week intervals with 2H2(18)O and basal metabolic rate (BMR): PA = ADMR/BMR. Ninety-six subjects, 66 females and 30 males, from 7 different studies were included. FFM and FM were adjusted for height by taking its ratio to the square of height, in analogy with the body mass index. Subsequently, all analyses were corrected for origin of the data. In a regression analysis FM explained 53 and 40% of the variation in FFM in females and males, respectively. Adding PA to the model raised the explained variation in FFM in females to 62%. In contrast with females (r = 0.10, n.s.), there was an independent relationship between PA and FM in males (r = -0.41, p less than or equal to 0.05), such that a higher PA was related to a lower FM. In conclusion, FFM is a function of FM and PA. The absence of an effect of exercise training on FFM, i.e. additional exercise in weight-reduction programmes, is discussed.

Adipose Tissue

Long-term effect of physical activity on energy balance and body composition.

We studied the effect of an increase in physical activity on energy balance and body composition without interfering with energy intake (EI). Sixteen women and sixteen men, aged 28-41 years, body mass index 19.4-26.4 kg/m2, not participating in any sport before the start of the experiment, prepared to run a half-marathon competition after 44 weeks. Measurements of body composition, EI and energy expenditure (EE) were performed before (0 weeks), and 8, 20, and 40 weeks after the start of training. Body composition was measured with hydrodensitometry and isotope dilution, and EI with a 7 d dietary record. EE was measured overnight in a respiration chamber (sleeping metabolic rate (SMR)) and in a number of subjects over 2-week intervals with doubly-labelled water (average daily metabolic rate (ADMR)). ADMR showed an average increase of 30% in both sexes from the start of training onwards while SMR tended to decrease. EI showed a tendency to drop from week 20 to week 40 in the men and a tendency to increase from week 20 to week 40 in the women. Body mass (BM) did not change in both sexes until the observation at 40 weeks when the median value of the change in men was -1.0 kg (P < 0.01; Wilcoxon signed-rank) while the corresponding change of -0.9 kg in the women was not statistically significant. Body composition changes were most pronounced in men as well. Based on changes in BM, body volume and total body water, men lost 3.8 kg fat mass (FM) (P < 0.001; Wilcoxon signed-rank) and gained 1.6 kg protein mass (P < 0.01; Wilcoxon signed-rank) while the corresponding changes in women were 2.0 kg (P < 0.05; Wilcoxon signed-rank) and 1.2 kg (P < 0.05; Wilcoxon signed-rank). In men the loss of FM was positively correlated with the initial percentage body fat (Pearson r 0.92, P < 0.001). In conclusion, body fat can be reduced by physical activity although women tend to compensate for the increased EE with an increased EI, resulting in a smaller effect on BM and FM compared with men.

Adult

Sleeping metabolic rate in relation to body composition and the menstrual cycle.

The relationship between sleeping metabolic rate (SMR) measured from 0300 to 0600 h in a respiration chamber and body composition was studied in 47 healthy adult subjects (23 men and 24 women). The effect of the menstrual cycle on SMR was examined in 16 of the 24 women. SMR increased in the postovulation phase of the menstrual cycle (estimated as days 18-29 after last menstruation) 7.7% on average (P less than 0.001). A stepwise regression showed that both fat-free mass (FFM), fat mass (FM), and the phase of the menstrual cycle contributed significantly to SMR. After adjustment for FFM and FM, no sex differences in SMR (men vs preovulation women) remained. The inclusion of FM in this model is an improvement that eliminates the sex difference in SMR/FFM that is usually found. A prediction equation is given that explains 85% of the variance in SMR among individuals.

Basal Metabolism

Syntactic structure analysis of the arrangement of nuclei in dysplastic epithelium of colorectal adenomatous polyps.

In search of new objective classifiers of the degree of dysplasia in colorectal adenomatous polyps, we conducted syntactic structure analysis on hematoxylin-eosin-stained tissue sections of 59 colorectal adenomas. The adenomas were subjectively graded as showing mild (n = 20), moderate (n = 20) or severe (n = 19) dysplasia in a double-blind examination by two pathologists. Using an interactive video-overlay measuring system, a minimum spanning tree was computed in 10 fields per specimen according to a strict measurement protocol. From each minimum spanning tree, such features as total line length, length of line segments, total number of points and number of points with one, two, three or four neighbors were derived. Simple descriptive statistics of these minimum spanning tree features were used to analyze differences between the three grades of dysplasia. Univariate analysis indicated that most of the variables used were suitable for discriminating between mild and moderate as well as between mild and severe grades of dysplasia. Only median minimum line length also showed significant differences between moderate and severe dysplasia. By means of a jackknifed stepwise discriminant analysis, an overall correct classification of mild versus moderate and severe dysplasia of 81.4% was achieved. It is concluded that syntactic structure analysis may have additional value in describing, in an objective and rapid way, the morphologic changes of dysplasia in colorectal adenomatous polyps.

Adenoma

The effect of a 5-month endurance-training programme on physical activity: evidence for a sex-difference in the metabolic response to exercise.

The effect of a 5-month endurance training programme on physical activity and average daily metabolic rate (ADMR) was studied. Subjects were 16 males and 16 females preparing for a half marathon. Total physical activity, measured using an accelerometer, had increased by 62% and 63% after 20 weeks in males and females, respectively. Physical activity during the non-exercise part of the day did not change although in males it tended to increase (15%, NS). The ADMR had increased significantly in males after 8 and 20 weeks (+2.3 and +3.3 MJ.day-1, respectively, P less than 0.05) and exceeded the net energy expenditure for endurance-training three to four times. In females no significant increase in ADMR was found (+1.5 and +1.3 MJ.day-1, after 8 and 20 weeks, respectively). In females the change in ADMR could be largely attributed to the net cost of running itself and a small increase (10%) in resting metabolic rate during the time of day they were awake. In males a discrepancy was observed between the increase of ADMR and the expenditure due to exercise and non-exercise activities. We suggest exercise stimulates habitual physical activity and diet-induced thermogenesis in males but not in females.

Adult

Body composition and sleeping metabolic rate in response to a 5-month endurance-training programme in adults.

This study examined the effect of exercise training on body composition and sleeping metabolic rate (SMR) in 15 men and 13 women who participated in a 20-week training programme aimed at running a half marathon. Body mass (BM) was measured after waking up, fasted and with an empty bladder. Body composition was assessed using densitometry. The SMR was measured from 0300-0600 hours during an overnight sleep in a respiration chamber. Assessment of SMR was at least 36 h after the last period of exercise training. After 20 weeks of endurance training no change in BM was observed. However, body composition changed significantly. On average men lost 2.4 kg body fat (P less than 0.01) and gained 1.7 kg fat free mass (FFM) (P less than 0.01). In women fat loss averaged 0.9 kg after 20 weeks (P less than 0.01), while FFM increased by 1.0 kg (P less than 0.05). Loss of fat mass was significantly larger in males (P less than 0.05). No changes in SMR were found, either in absolute terms, or when normalised for BM or FFM. Therefore, we have concluded that exercise training has no chronic, long-term effect on SMR. A possible explanation for this outcome in view of the different findings in similar studies is discussed.

Adult

Methods to assess physical activity with special reference to motion sensors and accelerometers.

Motion sensors may be applied for the assessment of physical activity. This paper reviews the evolution of these instruments from the mechanical pedometer to the electronic accelerometer. We conclude that for accurate assessment of physical activity under free living conditions the recently introduced accelerometer looks most promising, although little information was available regarding the reliability of these instruments. Subsequently, reliability of an accelerometer with a three-directional sensor was examined. Intrainstrument variation in a bench test was less than 8% during four measurements over a week. Interinstrument variation during treadmill experiments while subjects wore two accelerometers at the same time was on average 22% and was not improved after adjustment for differences found in the bench test. Reproducibility in the treadmill experiment was approximately 76, 85, and 95% at 3, 5, and 7 km/h, respectively. Bench testing revealed that the sensitivity of a piezoelectric element is prone to shifts, probably due to mechanical, electromagnetic, and/or temperature shock, which may be encountered during outdoor application. However, the relevance of the bench test in this study may be questioned, as results did not correspond with the findings in subjects. This needs further investigation.

Adult

Biomechanical vibration of the abdominal region during running and bicycling.

The incidence of gastrointestinal (GI) distress reported among long distance runners and not in practitioners of other sports with more gliding movements, such as bicycling, leads one to speculate that there is a difference in concussions and vibration of the GI region and that this may possibly be associated with the disparity in GI disorders. The present experiment was conducted to quantify the difference in vibration (accelerations/decelerations) of the GI region during running as compared to bicycling. An actometer was used which included a piezoelectric sensor. The sensor was placed on the abdomen of six subjects during identical trials of bicycling and running. Movement in three planes was detected by the sensor and recorded. The accelerometer output (AO) is an integral of these measurements. AO was used in making comparisons of the two types of movement, expressed as counts per minute. Mean AO was more than doubled in running, 859.5 +/- 130.1 (SD), versus bicycling, 425.8 +/- 149.5 (SD) (p less than .0001). The common assumption that running results in more body vibrations than bicycling has been substantiated and quantified. Although the differences are large, it can only be speculated that these differences explain the high frequency of GI symptoms among runners.

Abdomen

Physical activity and sleeping metabolic rate.

In the present investigation we determined metabolic rate during sleep (SMR) as a function of physical activity (PA) in normal daily life. Subjects were nine females and six males, with an average age of 30 yr (range 19-48) and an average Quetelet Index of 32 (range 14-62). The level of SMR was expressed as an index; SMI = SMR/BMR, where SMR was measured in a respiration chamber while subjects were asleep and basal metabolic rate (BMR) was calculated with the equation from Harris and Benedict. Physical activity, calculated from average daily metabolic rate (ADMR) and BMR, was expressed as an index: PAI = ADMR/BMR, where ADMR was measured with doubly labeled water and BMR was calculated as indicated above. Individual values of SMI were 0.8-1.2. SMI was positively correlated with PAI (r = 0.85, P less than 0.001). Subjects with either a high or a low Quetelet Index were concentrated in the lower range of PAI compared with normal-weight subjects. In conclusion, subjects with an extremely low or high body weight generally show a lower than expected SMR associated with a low physical activity.

Adult

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Anesthesia