Yasushi Toda

SMALL BOWEL TRANSIT TIME AND COLONIC FERMENTATION IN YOUNG AND ELDERLY WOMEN

Small bowel transit time (SBTT) in 15 young and 13 elderly women was assessed by measuring breath hydrogen concentrations after they had consumed a solid test meal. The meal consisted of 200 g cooked rice, 50 mlmiso (made from fermented soy bean curd) soup, a boiled egg, and 95.5 g of cooked soy beans with mixed vegetables. This meal provided 17 g protein, 14.1 g fat, 92.9 g carbohydrate, 7 g dietary fiber, and 565 kcal total energy. The SBTT, calculated by a 3 ppm increase in breath hydrogen, was 19±14.9 (mean±SE) min in the young and 188.1±16.8 min in the elderly group; the difference was not significant. Breath hydrogen levels, however, were higher in the young than in the elderly group (39.1±6.3 ppm, vs 22.2±4.3 ppm,P<0.05). There was an initial peak of hydrogen concentration, reached almost immediately after the ingestion of the meal, and then a decline to baseline within 60 min. This initial peak was not as pronounced in the elderly subjects. A second peak, indicating the entry of the test meal into the cecum, was more pronounced in the young than in the elderly group. SBTT did not differ significantly between the two groups, but colonic fermentation was more pronounced in the young, both in the fasting and the postprandial state.

Milk is a useful test meal for measurement of small bowel transit time

To improve and standardize the measurement of small bowel transit time, milk was employed for the test meal instead of the conventional lactulose meal. Although 92% of the subjects were lactase deficient, only 2% were milk intolerant and 13% were lactose intolerant. Small bowel transit time with milk (milk breath hydrogen test) was 113±9 min (mean ± SE,n=20); the normal range calculated from the mean ±2 SD was 31–195 min. The coefficient of variation in the milk hydrogen breath test was 13 ± 4% (n=6), whereas in the lactulose hydrogen breath test, it was 39±16% (n=10). The frequency of non-hydrogen producers, the occurrence of discomfort, and the reproducibility were better, though not significantly so, in the milk hydrogen breath test than in the lactulose. Since lactase activity in the intestine is variable in lactase-deficient subjects, small bowel transit times for milk may change from subject to subject. However, individual reproducibility of the milk hydrogen breath test is good. It could be useful for pharmacological experiments using paired comparison, for screening tests, or for the follow up of diseases in which small bowel transit time is affected.

The excretion of 5,5-dimethyl-2,4-oxazolidinedione from the canine pancreas and liver

With administrations of maximal and supramaximal doses of secretin, the excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) into pancreatic juice and bile was studied in the dog. When flow rate and bicarbonate concentration in both of the digestive juices were kept relatively constant by continuous intravenous infusion of secretin (2 units/kg/hr), DMO appeared promptly in them after the intravenous administration; the concentration decreased exponentially, as it did in arterial plasma during a 30-minute period. Equilibrium was achieved within 1 hour in both plasma and pancreatic juice, and nearly attained in 1 hour in both plasma and bile. With single rapid intravenous injections of secretin (2 units/kg and 4 units/kg), pancreatic DMO excretion depended directly on flow rate, bicarbonate concentration, and even on plasma level of the compound, while biliary DMO excretion was dependent at least on flow rate.

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione in narmal subjects

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) was studied in 25 normal subjects using the technique of the traditional pancreatic secretory test. The pancreozymin-secretin test was performed 4 days after the oral administration of trimethadione (3,5,5-trimethyl-2,4-oxazolidinedione, the precursor of DMO) for 3 consecutive days. When a dose of 1 unit/kg of pancreozymin was administered intravenously, both DMO concentration and output of a 10-min fractional specimen were rapidly increased and then decreased gradually. When a dose of 1 unit/kg of secretin was injected 30 min after pancreozymin, DMO concentration in duodenal aspirate showed no significant alteration, while DMO output of the aspirate was remarkably increased and then diminished in parallel to flow rate. DMO concentration in plasma varied widely from subject to subject, but was fairly constant during the course of the test in the same subject. Total DMO output in the postpancreozymin 30-min and postsecretin 60-min periods was linearly related to plasma DMO concentration. The output of DMO, when expressed as the output at a level of 10 mg/100 ml of plasma DMO, was linearly related to secretory volume and bicarbonate and amylase outputs in the postsecretin period. These results led to the conclusion that the human pancreas was capable of excreting a weak organic acid of DMO with a molecular weight of 129.1 and that the excretion of DMO in normal subjects was a function of two factors: plasma DMO concentration and pancreatic secretory volume.

Pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione in patients with chronic pancreatitis

Abnormal pancreatic excretion of 5,5-dimethyl-2,4-oxazolidinedione (DMO) was demonstrated in 44 patients with chronic pancreatitis (14 with calcification and 30 without calcification). Pancreatic excretion of DMO in patients with chronic pancreatitis, as well as in normal subjects, depended on plasma DMO concentration and secretory volume. In the postsecretin 60-min period, almost all patients showed a decrease in total DMO output of duodenal aspirate over the observed range of plasma DMO concentration. More than half the patients without calcification gave a discordant pattern between the DMO output and volume, ie, decreased DMO output with normal volume secretion, while most of patients with calcification had low DMO output with decreased volume flow. The data of the pancreozymin-secretin test suggested that chronic pancreatic inflammation was moderate or minimal in patients without calcification and far advanced in those with calcification. From these results the hypothesis was advanced that DMO diffusion into the pancreatic ducts might be primarily impaired in the relatively early stage of chronic pancretitis, and as the inflammation progressed to the final stage, DMO outflow from the ducts to the duodenum would be disturbed with evolving diffusion impairment of the compound. Total DMO output, when expressed as the output at a level of 10 mg/100 ml of plasma DMO (standard DMO output), was significantly reduced in chronic pancreatitis during a 60-min period after secretin stimulation. DMO in duodenal content, when expressed in terms of maximal concentration ratio of duodenal juice/plasma for the compound (maximalJ/P ratio), was significantly low in chronic pancreatitis during the last 40-min period after secretin stimulation. These two parameters can therefore be used as indices of pancreatic excretion of DMO. The present technique may well become an effective diagnostic tool for early detection of chronic pancreatitis.

Circadian rhythm of breath hydrogen in young women

Abstract: Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of α-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21–23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, α-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 ± 3.9 ppm (mean ± SE), which did not differ from the value for the previous night. α-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 ± 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day.

Effect of gastrin-releasing peptide (GRP) on guinea pig gallbladder contrction in vitro

Few studies have reported the effects of gastrin-releasing peptide (GRP)/bombesin on the guineas pig gallbladder, and the results are contradictory. Because such contradictory results may, in part, be due to technical factors, we investigated the effect of GRP on guinea pig gallbaladder smooth muscle, using a improved horizontal organ bath. The guinea pigs were killed and the gallbladder was removed. Four longitudinal uscle strips (2×12mm) were suspended in Krebs-Ringer solution at 37°C and aerated with 95% O2 and 5% CO2. The mechanical activity of the strips was recorded isotonically by displacement-voltage transducers. via L-arms, to which a piezoelectric element with a frequency of 100Hz and movement of 50μm was applied. GRP contracted gallbladder muscle strips dose dependently, but the calculated maximal response was 22.4% and 20.1% of the acetylcholine-and cholecystokinin octapeptide (CCK8)-induced responses, respectively. The GRP-induced contraction was unaffected by the muscarinic blocker, atropine, or by the CCK receptor antagonist, loxiglumide. It is concluded that GRP weakly, but apparently directly, stimulates guinea pig gallbladder contraction.

Secretory characteristics of pancreatic ?-glutamyl transpeptidase

SummaryIn an attempt to identify the secretory mechanism of pancreatic γ-glutamyl transpeptidase (γ-GTP), constant intravenous infusions of secretin alone and in combination with caerulein were performed in anesthetized dogs prepared with a pancreatic fistula. Caerulein produced a marked increase in amylase concentration and only a slight increase in γ-GTP. γ-GTP concentration of the pancreatic juice varied from 12 to 490 mU per ml which ranged up to 188-fold higher than that of the serum. The enzyme concentration depended largely on the flow rate, revealing 3 characteristic curvlinear relationship, regardless of whether caerulein was added to the secretin infusion. No significant relation was demonstrated between amylase concentration and flow rate, amylase and γ-GTP concentrations, and γ-GTP and protein concentration. An inverse linear correlation between γ-GTP and chloride concentrations was obtained when flow rate was below 2.5 ml per 15 min. A significant linear relationship was demonstrated between γ-GTP and leucine aminopeptidase concentrations, and amylase and protein concentrations. The results presented clearly demonstrate that the mechanism of pancreatic secretion of γ-GTP is quite distinct from that of amylase.

Comparison of detectability of elevated amylase of serum and urine in pancreatic diseases by two amylase assay methods using starch substrates of different digestive rates to pancreatic amylase

SummaryDetectability of abnormally high serum and urine amylases was investigated on patients with pancreatic diseases using amylase assays with substrates of different digestive rates to pancreatic amylase. Ratios of amylase activities determined by a chromogenic assay using a Remazolbrilliant Blue R starch (RBB assay) to those by Caraway’s assay using a Lintner soluble starch (R/C ratio) were calculated on duodenal and salivary amylases obtained from 16 subjects undergoing a pancreozymin-secretin test. The R/C ratio of the duodenal amylase (M ±SD = 0.56 ±0.12) was significantly higher (p<0.01 by F test) than that of the salivary amylase (M ±SD = 0.36 ±0.10). Detectability of above-normal values of serum and urine amylases were compared with two assays in 77 pancreatic patients. The value for serum and urine amylases determined by the RBB and Caraway’s assays exceeded the upper limit of normal in 37 and 58% by the RBB assay and 24 and 26% by Caraway’s assay, respectively. Degrees of abnormality (ratio of the observed to the upper normal value) in serum and urine amylases were also significantly higher (p<0.05 for serum and p<0.01 upper for urine) by the RBB assay than by Caraway’s assay. The RBB assay was more sensitive than Caraway’s assay in detecting elevation of pancreatic amylase in serum and urine.

Panel Discussion: Treatment of acute pancreatitis

The purpose of this report is to study the conservative t reatment of acute pancreatitis in early stage and period of convalescence. Tile subjects are 120 cases of acute pancreatitis; 47 cases confirmed operatively and 73 cases diagnosed clinically. Results are as follows: 1) The extent of the involvement of pancreas appeared to parallel the t ime that has elapsed before t reatment with fluid and electrolytes transfusion. I t is suggested that inadequate treatment during 48 hours from onset may aggravate not only symptoms of patients, but also impairment of the pancreas itsself. 2) The dosis of trypsin-inhibitor during 48 hours was sixty thousands units of Trasylol per one liter 0ftransfusion fluid in sever cases with a good course. A large dosis of trypsin-inhibitor, therefore, may be effective on acute pancreatitis, provided that sufficient transfusion is put into practice. 3) In the majori ty of cases who was given even a small amount of l iquid food within the first 48 hours, the patient s condition obviously deteriorated. Any case who had taken only a little during 4 days, appeared to have a high risk to be worsen. Complete starvation is the most important in the treatment over this period. 4) Therapy in early period of 10 severe cases with a good course was complete starvation with gastric suction, adequate transfusion (mean value: 3190ml/day), and sufficient dosis of trypsin-inhibitor (mean value: 260,000 Trasylol units/day) and antibiotics (mean value: 5 g of Cephalothin/