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Biomedical subjects

I C Roberts-Thomson

Publications and source records attributed to I C Roberts-Thomson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Placebo-controlled trial of dexamethasone for chronic biliary pain after cholecystectomy.

Activation of the sympathetic nervous system appears to be relevant in some patients with unexplained pain after cholecystectomy, particularly those who show increases in plasma transaminase activity after challenge with morphine (morphine responders). In this study, the hypothesis that dexamethasone would improve chronic biliary pain, perhaps by suppressing activation of the sympathetic nervous system, was tested in a double-blind, placebo-controlled, cross-over trial in 20 patients, 10 morphine responders and 10 nonresponders. Before treatment with dexamethasone and placebo, urinary excretion of norepinephrine (NE) was significantly higher (p less than 0.05) in morphine responders than in nonresponders. During treatment with dexamethasone, 1 mg each night for 4 weeks, neither morphine responders nor nonresponders showed a significant improvement in pain or nausea or a significant reduction in sympathoadrenomedullary activity as assessed by urinary excretion of catecholamines. At the dose administered, dexamethasone was unhelpful for chronic pain after cholecystectomy and did not result in suppression of the sympathetic nervous system as assessed by urinary excretion of NE.

Biliary Tract Diseases↗
PubMed1991

Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis.

Substantial amounts of phenols are produced in the human colon by bacterial fermentation of protein. In the colonic mucosa of animals, phenols are inactivated predominantly by conjugation with sulphate. The purpose of this study was to confirm sulphation of phenols by isolated colonocytes from man and to evaluate mucosal sulphation in inflammatory bowel disease using the phenol, paracetamol, in rectal dialysis bags. The incubation of paracetamol with colonocytes isolated from resected colon specimens (n = 7) yielded a mean (SE) value of 7.0 (0.9) mumols/g dry weight of paracetamol sulphate after 60 minutes but virtually undetectable values of paracetamol glucuronide. Paracetamol sulphate was detected in rectal dialysates from all control subjects, with a mean (SE) value of 4.2 (0.8) nmol/hour. Sulphation was significantly impaired (p less than 0.01) in 19 patients with active ulcerative colitis (0.6 (0.2) nmol/hour) and in 17 patients with ulcerative colitis in remission (1.1 (0.4) nmol/hour). Sulphation in eight patients with Crohn's colitis (4.3 (2.1) nmol/hour) was similar to that in control subjects. Impairment of the capacity of the mucosa to sulphate phenols in quiescent and active ulcerative colitis may pose a metabolic burden on colonic epithelial cells, which are continuously exposed to endogenous phenols from the colonic lumen.

Acetaminophen↗
PubMed1990

Pyruvate sparing by butyrate and propionate in proliferating colonic epithelium.

1. The effects of fasting and fasting followed by refeeding on the relative activities of the pyruvate dehydrogenase (PDH) complex and the tricarboxylic acid (TCA) cycle in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]pyruvate and [3-14C]pyruvate, respectively. 2. Decarboxylation of pyruvate by the PDH complex exceeded that by the TCA cycle in both fasted and fasted/refed colonocytes, was higher in distal than in proximal colon, and was stimulated by refeeding following a fast. 3. Oxidation of pyruvate by both the PDH complex and the TCA cycle was inhibited by butyrate. 4. Propionate alone had no effect, but synergized with butyrate to further reduce pyruvate decarboxylation by the TCA cycle. 5. Preferential utilization of butyrate by proliferating colonic epithelial cells is postulated to maximize the energy yield and spare pyruvate and its precursors for alternative synthetic roles necessary for active cell division.

Animals↗
PubMed1990

Sympathetic activation: a mechanism for morphine induced pain and rises in liver enzymes after cholecystectomy?

In patients with biliary type pain after cholecystectomy, morphine often precipitates pain and may induce rises in plasma concentrations of liver enzymes because of exaggerated or prolonged rises in intrabiliary pressure. In this study, changes in plasma concentrations of catecholamines and histamine were determined after the administration of morphine in patients with and without a two-fold or greater rise in the plasma concentration of aspartate aminotransferase at four hours. Those showing rises in aminotransferase had higher concentrations of noradrenaline at 40 and 60 minutes after morphine and higher concentrations of dopamine at 40 minutes after morphine. The two groups had similar concentrations of adrenaline and histamine. Attempts to inhibit rises in aminotransferase after morphine by pretreatment with histamine, serotonin and alpha-receptor blockers were largely unsuccessful, although inhibition was observed with phenoxybenzamine in two of five patients. Higher plasma concentrations of noradrenaline and dopamine before and soon after induction of pain in patients showing rises in aminotransferase are consistent with sympathetic activation but heterogeneity appears to exist in the response to alpha-receptor blockade.

Adult↗
PubMed1990

The effects of enterotoxins and short-chain fatty acids on water and electrolyte fluxes in ileal and colonic loops in vivo in the rat.

The effect of cholera toxin (CT) and Escherichia coli heat-stable enterotoxin (ST) on the ileum and colon was examined in vivo in the rat in an attempt to clarify the effects of enterotoxins on colonic mucosa and to determine if these effects were influenced by short-chain fatty acids (SCFA). Both CT and ST induced similar changes in water and electrolyte fluxes, and the magnitude of these changes in loops of colon was similar to that observed in loops of ileum. The addition of luminal SCFA, acetate, propionate and butyrate did not influence the effect of either toxin in loops of ileum. However, in loops of colon exposed to CT, luminal butyrate (40 mM) largely reversed the effect of CT by converting net water secretion (mean +/- SE, -363 +/- 154 nl.cm-2.min-1) to net water absorption (470 +/- 194 nl.cm-2.min-1) and by significantly reducing the net secretion of sodium ions. In loops of colon exposed to ST, similar effects were observed although net water secretion (-784 +/- 114 nl.cm-2.min-1) was only partially reversed by butyrate (-318 +/- 102 nl.cm-2.min-1). In contrast to butyrate, acetate and propionate did not influence changes in colonic fluxes of water and sodium induced by enterotoxins. Oxidation of butyrate and glucose was observed to be depressed in colonocytes pre-exposed to CT but not to ST. In this model, colonic secretion induced by enterotoxins is similar to that observed in the ileum but differs from ileal secretion in its modulation by luminal butyrate.

Animals↗
PubMed1990

Pentose phosphate pathway in rat colonic epithelium.

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.

Animals↗
PubMed1989

An assessment of proliferative and enzyme activity in transitional mucosa adjacent to colonic cancer.

The mucosa within 2 cm of cancers of the large bowel (transitional mucosa) shows histologic and histochemical changes which may indicate premalignant change. In this study, the authors used specimens from resected colonic tissue to compare morphometric, proliferative, and enzyme markers in transitional mucosa with those in cancer tissue and with those in uninvolved mucosa at least 10 cm from the cancer. Proliferative activity was assessed using the Ki 67 monoclonal antibody technique whereas a variety of methods were used to determine enzyme activities in mucosal homogenates. When compared to uninvolved mucosa, crypts in transitional mucosa contained greater number of cells, were significantly deeper and wider and were more likely to be branched. However, crypts in transitional mucosa had a significantly lower labelling index using the Ki 67 technique and there was no evidence of a shift in the proliferative zone towards the bowel lumen. The activities of ornithine decarboxylase, thymidine kinase, alkaline phosphatase, and lactate dehydrogenase were similar in transitional and uninvolved mucosa. Cancer tissue showed significantly higher levels of activity for ornithine decarboxylase and lactate dehydrogenase. Transitional mucosa showed morphometric changes but there were no proliferative or enzyme markers to suggest a higher than expected risk for malignant change.

Alkaline Phosphatase↗
PubMed1989

Estimation of phenolic conjugation by colonic mucosa.

Conjugation of phenol by the colonic mucosa was assessed in vivo using dialysis tubing containing 1.5 ml of 1 mmol/l acetaminophen (paracetamol) and 10 mmol/l butyrate. These were allowed to equilibrate in the rectum for one hour. The glucuronidated and sulphated conjugates of acetaminophen were measured by high pressure liquid chromatography and bicarbonate concentrations by gas analysis. In 21 subjects without colonic disease sulphate conjugation was observed in all cases, with a mean (SE) of 3.86 (0.66) nmol/hour, while glucuronide conjugation was found in seven of 21 cases. Mean (SE) bicarbonate output of 42.9 (3.9) mumol/hour (n = 21) indicated healthy colonic mucosal metabolism and phenolic sulphation in dialysate and agreed with published sulphation rates obtained with cultured cells of colonic epithelium. Acetaminophen sulphation suggests that the colonic mucosa has an important role in the conjugation of phenols, and the method reported here would be useful in assessing the detoxification capacity of the colonic mucosa in diseases of the rectal mucosa.

Acetaminophen↗
PubMed1988

Zinc deficiency is associated with suppression of colonocyte proliferation in the distal large bowel of rats.

As zinc status may influence susceptibility to colon cancer, we examined the effect of dietary zinc deficiency on the proliferation of epithelial cells (colonocytes) in the large bowel of rats. When compared to feed-restricted rats, those with zinc deficiency showed a significant reduction in proliferation in the distal colon as assessed by accumulated metaphase arrest and crypt cell production rates in vivo. Zinc deficiency had no apparent effect on thymidine kinase activity in colonocytes but was accompanied by minor changes in fecal mass and fecal pH. In rats, zinc deficiency is associated with a reduction in the rate of proliferation of colonocytes in the distal colon.

Animals↗
PubMed1988

Proliferative activity in the proximal and distal colon of the rat after fasting and refeeding.

Several methods were used to assess proliferation of colonocytes in the proximal and distal colon of the rat after fasting and refeeding. Those applied in vivo included metaphase arrest, labelling with bromodeoxyuridine and uptake of tritiated thymidine. The latter two techniques were also applied after isolation of colonocytes in vitro. Methods applied in vivo showed similar proliferation in the proximal and distal colon after fasting and enhanced proliferation in both regions after refeeding. However, the degree of enhancement was greater in the distal colon than in the proximal colon. In vitro, proliferation was enhanced in both the proximal and distal colon after refeeding but the degree of variability was greater than after assessment in vivo. Methods applied in vivo are preferred for assessment of proliferative activity in the rat colon, and major changes in proliferation in both proximal and distal colon can be induced by fasting-refeeding.

Animals↗
PubMed1988

Circadian rhythms in patients with abdominal pain syndromes.

Circadian rhythms for cortisol, 6-sulphatoxy melatonin and core body temperature were compared in control subjects and patients with functional abdominal pain. There were 20 patients with biliary pain after cholecystectomy, ten with biliary pain without cholecystectomy and 14 with irritable bowel syndrome. Rhythms were determined by urine collections at intervals of 4 h for 48 h and by overnight monitoring of core body temperature using the Vitalog system. Data were fitted to a sine curve to yield the time of maximal urinary excretion/lowest temperature and the amplitude of each rhythm. Urinary excretion of free cortisol was similar in patients and control subjects. For urinary 6-sulphatoxy melatonin, the timing (phase) of rhythms was similar in patients and controls but those with pain had a lower urinary excretion of 6-sulphatoxy melatonin (p less than 0.05) and a rhythm of lower amplitude (p less than 0.02). The amplitude of the temperature rhythm was also lower in patients with biliary pain with and without prior cholecystectomy (p less than 0.05). Functional abdominal pain is associated with 6-sulphatoxy melatonin and temperature rhythms of low amplitude, presumably because of suppression of circadian oscillators.

Abdomen↗
PubMed1987

Evidence against an immunogenetic basis for diabetes in chronic pancreatitis.

A possible immunogenetic basis for diabetes in chronic pancreatitis was explored by studying 19 patients with both disorders, most of whom required treatment with insulin. In contrast to patients with insulin-dependent (Type 1) diabetes, patients with diabetes and chronic pancreatitis had residual beta cell function but blunted C-peptide responses to intravenous glucagon, absence of circulating islet cell antibodies, and HLA-DR types similar to control subjects and patients with chronic pancreatitis without diabetes. Diabetes complicating chronic pancreatitis is therefore not associated with the biochemical or immunogenetic markers characteristic of Type 1 diabetes.

Adult↗
PubMed1986

Assessment of bile flow by radioscintigraphy in patients with biliary-type pain after cholecystectomy.

Scintigraphy of the biliary system using 99mTc di-isopropyl iminodiacetic acid (DIDA) was performed in 65 subjects who had previously undergone cholecystectomy. Of the 65 subjects, 20 were free of pain and 45 had biliary-type pain both with (group I) and without (group II) features of sphincter of Oddi dysfunction. This dysfunction comprised dilatation of the bile duct, a transient rise in serum levels of liver enzymes after episodes of pain, or both abnormalities. After computer acquisition of images at intervals of 60 seconds for at least 90 minutes, time/activity curves were generated for five regions of interest: liver, common hepatic duct, common bile duct, duodenum, and background. The time at which counts in the common bile duct reached 50% of maximum (CBD T50) and the time of first entry of isotope into the duodenum (TD) were used to compare asymptomatic subjects with those with biliary-type pain. Patients in group I, but not those in group II, showed significant prolongation of CBD T50 (p less than 0.002) and TD (p less than 0.02) when compared to values in asymptomatic subjects. Six patients had a second scan at six to 12 months after endoscopic sphincterotomy and all showed a reduction in values for CBD T50 and TD. In patients with pain, a significant correlation was shown between bile duct diameter and CBD T50 (p less than 0.01) and between bile duct diameter and TD (p less than 0.02) but results from scintigraphy were independent of responses to morphine-neostigmine and motility in the sphincter of Oddi as assessed by endoscopic manometry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Sphincter of Oddi motility disorders in patients with idiopathic recurrent pancreatitis.

Motor disorders of the sphincter of Oddi (SO) may play a role in the pathogenesis of idiopathic recurrent pancreatitis. We have compared manometric records from the SO in 28 patients with idiopathic recurrent pancreatitis with those from 10 control subjects. Patients with idiopathic recurrent pancreatitis had presented with episodes of upper abdominal pain associated with abnormal serum levels of amylase on at least two occasions, in the absence of alcohol abuse and biliary disease. Retrograde pancreatography was either normal or showed only minor changes in pancreatic ducts. A triple lumen low compliance manometric system was used to obtain a 5 min recording of spontaneous SO motor activity. From this recording were determined the SO basal pressure, SO phasic contraction amplitude, SO wave frequency and direction of wave propagation. The SO response to intravenous cholecystokinin-octapeptide (CCK-OP) 20 ng/kg was then recorded for at least 3 min. Twenty-five of the twenty-eight patients demonstrated one or more manometric abnormality when compared with data from the ten controls. The most frequent abnormality was an elevated SO basal pressure in 16 patients. In addition, excess of retrograde contractions in nine patients, high frequency of SO phasic contractions in nine patients, absence of phasic contractions in three patients, and paradoxical response to CCK-OP administration in two patients were recorded. This study has demonstrated a spectrum of sphincter of Oddi manometric disorders in patients with idiopathic recurrent pancreatitis and suggests that motility disorders of the sphincter of Oddi may be associated with episodes of pancreatitis.

Adult↗