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Biomedical subjects

D B Silk

Publications and source records attributed to D B Silk.

At least 73 records · Page 4Linked to original sources

Gastrointestinal carcinoid tumours in a district general hospital. Review of a three-year consecutive series.

A consecutive series of gastrointestinal carcinoid tumours presenting over a 3-year period at a district general hospital is reported. None were diagnosed at autopsy. Sites of origin from fore-, mid- and hind-gut were all represented. Sixty-three per cent of patients had tumour-related symptoms at presentation. Of these 90% had nodal metastases and 60% had liver metastases. Carcinoid syndrome developed in most patients with liver metastases. The presentation and management of carcinoid tumours is discussed.

Adolescent↗

Effect of cholecystectomy on mouth-to-cecum transit of a liquid meal.

Mouth-to-cecum transit and serum bile acid profile after ingestion of a lactulose-labeled liquid meal (440 kcal) were measured in eight patients with gallstones and a radiologically functioning gallbladder before and three to five months after cholecystectomy and in 15 controls. In the patients mouth-to-cecum transit was longer after the operation, 87.5 +/- 18.5 (mean +/- SEM) min vs 57.5 +/- 9.7 min (P less than 0.05). Mouth-to-cecum transit times before and after the operation were not different from controls (58.0 +/- 6.7 min). Serum bile acid AUCs were similar (P = NS) in patients and controls, while total bile acid and cholylglycine fasting concentrations were higher after cholecystectomy (P less than 0.05 and P less than 0.01 respectively). Cholecystectomy prolongs mouth-to-cecum transit of a liquid meal.

Adult↗

Assimilation of lactitol, an 'unabsorbed' disaccharide in the normal human colon.

The fate of orally ingested lactitol, a non-absorbed sugar, was measured in six healthy human subjects by following the three routes of disposal of universally 14C-labelled sugar. Lactitol was given as a 20 g daily dose to six healthy volunteers for 14 days and on the seventh day, 10 muCi of L-[U-14C]-lactitol was given with the unlabelled sugar and excretion of the 14C in breath, urine and faeces was followed. The peak of 14CO2 excretion occurred at six hours and total 14CO2 accounted for 62.9 (5.0)% of isotope given, whilst 6.5 (3.6)% and 2.0 (0.3)% of the label were recovered from faeces and urine respectively. These data suggest that lactitol is extensively metabolised in the human colon and that a significant proportion of the bacterial metabolites are available for colonic absorption. Calculation revealed that 54.5% of the theoretical energy content of this compound was utilised by the subjects. It is suggested that this sugar, and other soluble 'non-absorbed' sugars (lactulose, sorbitol, mannitol), may undergo a similar pattern of colonic metabolism and can be considered as reduced calorie compounds.

Adult↗

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions.

Adult↗

Adult acquired cytomegalovirus infection with gastric and duodenal ulceration.

Recent reports of cytomegalovirus associated colonic and oesophageal ulceration in immunosuppressed patients infected with the human immunodeficiency virus, have focused attention on the possibility that viral infections may in some cases be the initial insult which leads in susceptible subjects to gastrointestinal ulceration. In this case report we describe how systemic primary infection with the cytomegalovirus was associated with the development of multiple gastric and duodenal erosions.

Adult↗

Laxative abuse.

Two types of laxative abuse are described, namely habitual abuse and surreptitious abuse. Phenolphthalein and the anthraquinone derivatives have been most abused in this respect. Long-term anthraquinone use may lead to melanosis coli and cathartic colon, with typical histological and radiological features. Surreptitious abuse presents as a factitious illness with diarrhoea, hypokalaemia, abdominal pain and thirst, as well as melanosis coli. Over 90% of cases occur in women, many of whom work in a paramedical situation. Wider recognition of the range of normal bowel habit and a cultural change with rejection of Victorian mores and concepts of 'intestinal auto-intoxication' have led to a decrease in inappropriate laxative consumption. However, they are still widely prescribed and bought. Although it was as long ago as 1937 that Witts [108] drew attention to the dangers associated with the use of laxatives, his lesion still needs to be preached today.

Cathartics↗

Familial granulomatous hepatitis: a hitherto unrecognized entity.

Two West Indian parents and three of their seven offspring presented over a 12-yr period with identical systemic illnesses characterized by the development of granulomatous hepatitis. Granulomata were variably also found in muscle, lymph nodes, and pleura in some of these affected individuals. The usual causes of granulomatous hepatitis were absent, and this familial disease represents a hitherto undescribed entity.

Adolescent↗

Effect of peptide chain length on absorption of egg protein hydrolysates in the normal human jejunum.

The influence of the peptide chain length of partial enzymic hydrolysates of protein on nitrogen and amino acid absorption was studied in 12 subjects using a jejunal perfusion technique. Three hydrolysates of egg white and an equivalent amino acid mixture were perfused at 30 mmol/L and 100 mmol/L in two separate experiments. Two hydrolysates (OH1 and OH2) contained mainly dipeptides and tripeptides, whereas the third (OH3) comprised tripeptide to pentapeptides as judged chromatographically. Nitrogen absorption was significantly slower from the higher chain length mixture, OH3, than from the short chain mixtures, OH1 and OH2, at both concentrations. Similarly, several amino acid residues were absorbed less well from OH3 than from OH1 and OH2. These data demonstrate that the chain length of heterogeneous mixtures of peptides affects absorption of nitrogen and individual amino acid residues, and suggest that brush border hydrolysis of tetrapeptides and pentapeptides limits absorption from enzymic hydrolysates of protein which simulate the composition of the postprandial luminal contents.

Amino Acids↗

Delayed postprandial plasma bile acid response in coeliac patients with slow mouth-caecum transit.

Coeliac patients are known to have an expanded bile salt pool which recirculates slowly due, at least in part, to impaired gall bladder contractility. We have investigated the possibility that delayed small bowel transit of chyme and bile may also contribute to this sluggish recycling. Plasma cholylglycine, total bile acids and cholecystokinin concentrations were measured after a lactulose-labelled test meal whose mouth-caecum transit time (M-C TT) was assessed by the breath hydrogen technique. Overall there were no significant differences in plasma bile acid profiles between seven healthy controls and a group of 25 coeliac patients. However, when subjects were divided according to their M-C TT, the 10 with the slowest transit were found to have significant elevation of fasting levels when compared with the 10 with the fastest transit, fasting total bile acids being 3.4 +/- 1.3 versus 0.7 +/- 0.6 mumol/l (P less than 0.02) and fasting cholylglycine being 0.43 +/- 0.17 versus 0.06 +/- 0.04 mumol/l (P less than 0.05) respectively. Peak bile acid levels did not differ significantly between subjects with fast or slow transit. However, subjects with slow transit were found to have a delay in the return of plasma bile acid levels to fasting levels so that the 4 h postprandial levels were significantly elevated when compared with those observed in the subjects with fast transit (total bile acids 3.6 +/- 1.2 versus 0.19 +/- 0.1 mumol/l and cholylglycine 0.70 +/- 0.13 versus 0.24 +/- 0.07 mumol/l respectively, both P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Glucose absorption from maltotriose and glucose oligomers in the human jejunum.

The jejunal absorption of glucose from (1-4)-linked glucose oligomers including maltotriose has been compared with that from free glucose and sucrose in normal subjects. A steady-state perfusion technique in vivo was used to study proximal jejunal assimilation of isotonic sugar-saline solutions isocaloric with 140 mmol/l glucose. Endogenous alpha-amylase was excluded from the test segment by proximal balloon occlusion. The glucose oligomer mixture consisted mainly of maltotriose, maltotetraose, maltopentaose and maltoheptaose. Glucose absorption was significantly faster from maltotriose alone and from the glucose oligomer mixture than from 140 mmol/l glucose controls, whereas glucose absorption from 70 mmol/l sucrose was similar to that from 70 mmol/l glucose plus 70 mmol/l fructose. Hydrolysis in vivo of maltotriose, the oligomer mixture and sucrose were similar, indicating that capture of glucose released by brush border sucrose hydrolysis was less efficient than that associated with (1-4)-linked oligomer hydrolysis. This suggests that the stoichiometric relationship of the active hydrolysis sites for sucrose to the glucose transport system is less advantageous than that of active sites for maltose hydrolysis. Hydrolysis of oligomers larger than maltohexaose may be rate limiting for glucose absorption in the absence of luminal amylase activity.

Chromatography, Gel↗

Lactitol, a new hydrogenated lactose derivative: intestinal absorption and laxative threshold in normal human subjects.

In the first part of the study, the absorption of lactitol, a new disaccharide analogue of lactose, was studied using an in vivo jejunal perfusion technique in man. Intestinal uptake of lactitol from isotonic solutions containing 10, 30, 60, and 100 mmol lactitol/l was insignificant. In the second part of the study the laxative threshold of lactitol was determined and compared with that of sorbitol in a double-blind, randomized, cross-over study on twenty-one normal subjects. Laxative threshold was considered to be either the maximum dose tolerated without unacceptable diarrhoea or gastrointestinal side effects, or when the maximum dose in the study was reached. Increasing amounts of lactitol, sorbitol or placebo were administered in two divided doses each day until subjects developed diarrhoea or severe gastrointestinal side effects. The laxative threshold of lactitol (74 (SE 5) g/d) was similar to that of sorbitol (71 (SE 5) g/d). These findings indicate that lactitol is not absorbed by the human small intestine. Although diarrhoea or other gastrointestinal side effects occurred as the dose was increased, 40 g lactitol/d was well tolerated.

Adult↗

Bowel sounds.

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Enteral Nutrition↗

Delayed mouth-caecum transit of a lactulose labelled liquid test meal in patients with steatorrhoea caused by partially treated coeliac disease.

Mouth-caecum transit time (M-CTT) of a lactulose labelled liquid test meal has been measured in 27 coeliac patients and 10 healthy controls using the breath hydrogen technique. Although all patients were urged to maintain a gluten free diet, not all did, and there was, therefore, a wide range in the severity of fat malabsorption within the patient group. Gastric emptying of a 113Indium DTPA-labelled liquid test meal was also assessed in separate studies on six healthy controls and 11 of the coeliac patients. Fasting breath hydrogen concentrations and the response to lactulose, as assessed both by the rate of rise, and the peak breath hydrogen concentration reached, showed no difference between coeliacs and controls, regardless of the presence or absence of steatorrhoea. Mouth-caecum transit time in the 16 coeliac patients with steatorrhea (faecal fat greater than 7 g/24 h) was, however, significantly prolonged being 158 +/- 18 minutes (mean +/- SEM), compared with 70 +/- 9 minutes for the controls (p less than 0.02), and 83 +/- 15 minutes for the 11 coeliacs without steatorrhoea (p less than 0.002). Mouth-caecum transit time in the coeliac patients was linearly related to the 24 hour faecal fat excretion, r = 0.55, n = 27, p less than 0.01. Slow mouth-caecum transit in the coeliacs with steatorrhoea was not caused by delayed gastric emptying as the t1/2 for coeliacs with steatorrhoea was within the normal range. Coeliacs with delayed mouth-caecum transit had impaired insulin release but the postprandial profiles of the other peptides measured (cholecystokinin, GIP, secretin, motilin, neurotensin, enteroglucagon, and peptide YY) were all within the normal range in this group of partially treated coeliac patients.

Adult↗

Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy.

Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6.51 +/- 0.48 vs lactitol -5.63 +/- 0.50; lactulose -5.18 +/- 0.82, p less than 0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.

Colon↗

Jejunal water and electrolyte absorption from two proprietary enteral feeds in man: importance of sodium content.

Jejunostomy losses of Na+ and water during enteral nutrition after massive intestinal resection may be severe. We have attempted to analyse this practical problem by using an in vivo perfusion technique in healthy volunteers to study Na+, water and nutrient absorption from a short (25 cm) segment of jejunum during perfusion of an isotonic solution of the elemental diet Vivonex. Further solutions made from the amino acid and carbohydrate components of Vivonex were also perfused in part I of the study in order to determine the causes of the marked Na+ and water secretion seen during Vivonex perfusion. Low initial Na+ concentration was found to be the major determinant of net Na+ secretion, initial Na+ concentration correlating significantly with Na+ absorption (r = 0.95, n = 7 p less than 0.001). Water absorption correlated with net absorption of NaCl (r = 0.82, n = 7 p less than 0.01). There was, however, a better correlation with total absorption of NaCl plus amino acids (r = 0.99, n = 7, p less than 0.01). In part II of the study separate isotonic solutions of NaCl, glucose, and the polymeric diet, Ensure were also studied. Net sodium secretion occurred during glucose and Ensure perfusion, as predicted from their low Na+ concentration. Owing to rapid sucrose absorption from Ensure there was substantial luminal disappearance of osmotically active particles and hence marked water absorption, which was accurately predicted using the regression equation for water absorption derived in part I, substituting sucrose absorption for amino acid absorption. We conclude that the marked Na+ and water secretion observed during Vivonex perfusion is not a unique property of this amino acid based diet but is due to its low Na+ content.

Amino Acids↗