Pierre Arhan

Segmental colonic transit time

Mean segmental transit time of radiopaque markers through the right colon, left colon and rectosigmoid areas of adults and children has been calculated from their distribution on consecutive plain films of the abdomen. Overall mean transit does not differ significantly in the large bowel between adults and children. However, there are regional differences within the colon in relation to age. Mean transit time in the right colon is 13.8 hours in adults and 7.7 in children (p<0.01). Corresponding values in the left colon are 14.1 and 8.7 hours (p<0.02) and, in the rectum, 11 and 12.4 hours (p=NS). The percentage of the mean total large bowel transit time spent in the right colon, left colon and rectosigmoid area are respectively for adults and children 33±4 and 28±3 per cent (p=NS); 39±4 and 32±4 per cent (p=NS); and 28±4 and 41±4 per cent (p<0.05), indicating a relative stagnation in the rectosigmoid area of children. These physiologic differences may have implications in diseased states.

What is the meaning of colorectal transit time measurement

This study was done to understand the different available methods used to calculate colorectal transit times. A single abdominal radiograph is taken following six successive daily ingestions of the same number of identical radiopaque markers. This method correlates well (P< 0.001) with that using a single ingestion of markers with daily x-ray films until total expulsion. In techniques used to measure colorectal transit time with multiple ingestion of markers, the number of days of ingestion depends on the kinetics of marker defecation. This was found to differ markedly in various groups of control subjects and constipated patients (P< 0.001) and can be used to obtain reliable data, even in subjects with severe constipation. When they ingest 20 markers, constipated patients are found to retain eight or more markers three days after ingestion, and taking a plain film of the abdomen on that day is sufficient to make a diagnosis of constipation. Transit time studies are reproducible from month to month in patients with an irritable bowel syndrome. Control subjects who claim that their bowel habits are not modified by stress have shorter transit times, similar in both sexes, than those who say they are (P<0.001). This may explain why a large percentage of constipated patients have been found by most authors to have “normal” colorectal transit times. The choice of control subjects is thus a key element in studies of functional bowel motor disorders. Stool frequency and consistency, in health, correlate only to rectosigmoid transit time.

Comparative Esophageal and Anorectal Motility in Scleroderma

Esophageal and anorectal pressures were recorded in 26 patients (4 men and 22 women) with scleroderma. Eleven patients suffered from a localized form of the disease and 15 from progressive systemic sclerosis. The latter only had marked functional abnormalities in esophageal and anorectal motility. Mean resting pressure at the lower esophageal sphincter of patients with progressive system sclerosis and controls was, respectively, 6 +/- 2 and 25 +/- 1 mmHg (p less than 0.001); mean closing pressure was 5 +/- 5 and 48 +/- 3 mmHg (p less than 0.001); coordination of opening the lower esophageal sphincter with the oncoming contraction in the distal esophagus was 0% and 68% +/- 5% (p less than 0.001); and relaxation (fall of the lower esophageal sphincter pressure to resting levels in the stomach) was 18% +/- 12% and 98% +/- 1% (p less than 0.001). The rectoanal inhibitory reflex was of lesser amplitude than normal in 74% of patients with progressive system sclerosis and was absent in 13%. Quantitative analysis demonstrated a significant reduction in response to rectal distention with 20 or more ml of air (p less than 0.001). There was a correlation between the amplitude of the lower esophageal sphincter relaxation and the amplitude of the rectoanal inhibitory reflex in response to rectal distention with 30-50 ml of air (p less than 0.05 to p less than 0.025). Our data show that in systemic sclerosis, anorectal motility is as frequently abnormal as esophageal motility.

Milk proteins and iron absorption: contrasting effects of different caseinophosphopeptides.

Clusters of phosphoserine residues in cow milk caseins bind iron (Fe) with high affinity. Casein inhibits Fe absorption in humans, but protein hydrolysis lessens this effect. Phosphopeptides from different caseins gave conflicting results on Fe absorption; release of phosphate residues by intestinal alkaline phosphatase could be a key point of that metabolism. The objectives of this study were to compare the absorption of Fe complexed to caseinophosphopeptides (CPP) of the main cow milk caseins β-casein (β-CPP) and αs-caseins (αs1-CPP) and to assess the role of alkaline phosphatase on this absorption. Two experimental models were used: an in vivo perfused rat intestinal loop and an in vitro Caco-2 cell culture model. In addition, we determined the effect of an intestinal phosphatase inhibitor on these various forms of Fe. Gluconate Fe was used as control. In both models, uptake and net absorption of Fe complexed to CPP from αS1-caseins were significantly lower than from Fe complexed to β-CPP. Inhibition of the intestinal phosphatase significantly increased the uptake and the absorption of Fe complexed to β-CPP without effect on the other forms of Fe. These results confirm the enhancing effect of β-casein and its CPP on Fe absorption. The differences between CPP could be explained by their structural and/or conformational features: binding Fe to αS1-CPP could impair access to digestive enzymes, whereas β-CPP–bound Fe is better absorbed than its free form. The differences in protein composition between cow and breast milk, which does not contain α-casein, could explain some of their differences in Fe bioavailability.

Mechanisms of absorption of caseinophosphopeptide bound iron.

Binding iron (Fe) to the 1-25 caseinophosphopeptide obtained from enzyme hydrolysis of beta casein (beta CPP) improves Fe bioavailability in the rat. To assess the mechanisms involved in its absorption, a perfused, vascularized duodenal rat loop model was used in controls and in Fe-deficient (bleeding of 25% blood volume) rats. Inhibitors of oxidative phosphorylation [2-4 dinitrophenol (DNP)] and/or of endocytosis [phenylarsine oxide (PAO)] were added to the perfusion solution containing 50 microM Fe as beta CPP bound Fe (Fe-beta CPP) or gluconate (Fe Gluc). Fe-beta CPP enhanced Fe uptake, reduced mucosal storage, and improved net absorption both in controls and in deficient animals. DNP reduced uptake, mucosal storage, and net absorption by the same percentage in Fe-beta CPP and Fe Gluc perfused rats in both control and Fe-deficient animals. PAO decreased uptake, mucosal storage, and net absorption of Fe-beta CPP but not of Fe Gluc. At the end of the experiment Fe serum levels were increased only in Fe Gluc animals. These results confirm the improved bioavailability of beta CPP bound Fe. They suggest that at least part of its absorption can occur by a different pathway than usual Fe salts. Fe-beta CPP can be taken up by endocytosis and absorbed bound to amino acids or peptides.

Aluminium increases xanthine oxidase activity and disturbs antioxidant status in the rat.

The mechanisms responsible for the neurotoxic effects of Al remain poorly understood. In order to determine whether Al promotes oxidative stress in vivo, we measured the enzymatic activity of xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione-S-transferase (GST) and glutathione reductase (GR) in four groups of rats after eight days of intraperitoneal administration of variable concentrations of Al (0, 5, 10, and 15 mg/kg body weight, respectively). XO activity was measured in both plasma and liver samples, and the activities of the remaining enzymes were further determined in the brain and red blood cells (RBC). The most significant changes were observed in XO and GPX activities, that were enhanced and depressed, respectively. In both instances, the enzyme activities were correlated with Al concentrations, either positively (XO) or negatively (GPX). Enhancement of XO and inhibition of GPX activity may lead to the accumulation of intermediate toxic compounds such as hydrogen peroxide and hydroxyl radicals, since SOD activity is increased as well. The latter finding must be taken with some caution because previous studies have shown contradictory results in this field. Our data suggest that Al toxicity could be mediated by its action on both pro- and anti-oxidant enzymes. The biological significance of these findings remains to be established.

Quantitative analysis of anorectal pressures in Hirschsprung's disease.

Anorectal motility was investigated in 146 children with Hirschsprungs disease and 89 normal control subjects. Pressures were recorded in the rectum and anal canal at rest and during rectal distention. The rectoanal inhibitory reflex was absent in all but four patients. Intraluminal rectal pressure was higher than normal (16.5 vs. 14.6 cm H2O,P<0.03), with more frequent (41 per cent vs. 18 per cent,P<0.01) pressure waves. In the upper anal canal, there were more frequent (62 per cent vs. 18 per cent,P<0.001) spontaneous variations of pressure of lower frequency (9.5 vs. 12.8 cycles/minP<0.001) and greater amplitude (5.2 vs. 3.6 cm H2O,P<0.001) than normal. The rectoanal contractile reflex occurred in 47 per cent of the patients but in only 21 per cent of the control subjects (P<0.001). Aganglionosis was associated with the presence of a rectoanal inhibitory reflex in three patients. This study confirms the value of anorectal manometry in diagnosing Hirschsprungs disease in a large group of patients, and demonstrates other abnormalities that may be useful in cases in which histologic and manometric data are in conflict.

Ischemic Fecal Incontinence and Rectal Angina

In 36 patients who consulted for fecal incontinence or rectal pain, or both, there was grossly visible scarring of the rectum and biopsy revealed mucosal atrophy and fibrosis. A steal from the hemorrhoidal arteries to the iliac vessels was demonstrated in 3 subjects. Maximum tolerable volumes within a rectal balloon were smaller than in control subjects, both in men (192 vs. 273 ml) and in women (142 vs. 217 ml) (p less than 0.01). The rectoanal inhibitory reflex was abnormal in all but 1 patient. Specific abnormalities were a decreased amplitude or a prolonged duration of the reflex. It was totally absent in 2 patients. This study is compatible with the hypothesis that chronic ischemia of the rectum may cause fecal incontinence or rectal pain.

Different segmental transit times in patients with irritable bowel syndrome and "normal" colonic transit time: is there a correlation with symptoms?

AbstractBackgroundThe Rome criteria serve as gold standard for establishing a diagnosis of irritable bowel syndrome (IBS), but only represent a cluster of symptoms. On the other hand, measurement of colonic transit time (CTT) with radiopaque markers is a solid and more objective method to quantify functional abnormalities. The goal of this study was to investigate whether the IBS symptoms, as defined in the Rome II criteria, correspond to objective physiological parameters, i.e. CCTs.MethodsThe study enrolled 148 healthy control subjects and 1385 consecutive IBS patients. Transit times were measured for the whole rectocolon (overall CTT) and for 3 segments (right colon, left colon, rectosigmoid area); segmental distribution of markers and diffusion coefficients were also assessed. In order to analyze homogeneous groups, we restricted analysis to subjects with “normal” CTT (≤70 hours).ResultsSix hundred forty four IBS patients (46%) and 14 control subjects (9%) had CTT >70 h and were eliminated. In subjects with CTT ≤70 h, CTT did not follow a normal (Gaussian) distribution. We identified 3 different CTT clusters in healthy controls and 4 clusters in IBS patients. Even if CTT was not significantly different between clusters, each cluster was characterized by a specific pattern of segmental colonic transit. There was a marked gender difference: women had longer overall CTT values than men, both in control and IBS patient groups (p<0.001). However, female IBS patients had significantly shorter colorectal transit times than female controls (p<0.001), as well as faster transit than in men through the left colon and rectosigmoid area. There were no significant differences in transit time between male IBS patients and male controls with the exception of a faster rectal transit in IBS patients (p<0.01). There was no association between segmental colonic transit values and sign or symptoms comprising the Rome II criteria.ConclusionsIn subjects with CTT ≤70 h, CTT does not follow a normal distribution but is clustered in subgroups that can be distinguished only by measuring segmental colonic transit. Within these subgroups, there is a marked difference in transit times between IBS patients and normal subjects, suggesting that IBS patients with “normal” CTT are not “normal”. The Rome II criteria do not reflect differences in segmental transit times in IBS patients with “normal” CTT. We therefore propose to evaluate segmental transit times in IBS patients with “normal” CTT, before and after treatment, in order to correctly interpretate variations in signs and symptoms. These findings have important implications in evaluating the effect of drugs on bowel function and should help define better inclusion criteria for studies evaluating new drugs for the treatment of IBS.

Comparison of fat oxidation during exercise in lean and obese pubertal boys: clinical implications

Objective: To examine fat oxidation rates during exercise in lean and obese pubescent children. Design: A graded leg cycle ergometry test was performed by two groups of pubescent boys (13 lean: mean (SD) age 12.0 (0.5) years, body mass index (BMI) 18.56 (1.12) kg/m2; 17 obese: mean (SD) age 12.1 (0.1) years, BMI 26.68 (3.37) kg/m2; p<0.001). The first step of the test was fixed at 30 W and power was gradually increased by 20 W every 3.5 min. The mean ventilatory gas measurement was obtained during the last 30 s of each step for calculation of fat oxidation rate vs exercise intensity. Results: At low intensity (0–30% of peak oxygen consumption) when fat-free mass is considered, the fat oxidation rate was identical for the two groups. At higher intensities (40%, 50% and 60% of peak oxygen consumption) the fat oxidation rate was significantly higher in lean boys than in obese boys. Conclusion: These results confirm that obese pubertal boys have fat-free mass decreased capacities to use fat during moderate exercise. The findings suggest that obese boys need to practise physical activity at a lower intensity than healthy boys to enhance lipolysis and diminish adipose tissue and the consequences of obesity.