PubMed Health⌕ Search

Biomedical subjects

D P Maudgal

Publications and source records attributed to D P Maudgal.

At least 19 recordsLinked to original sources
PubMed1991

A practical guide to the nonsurgical treatment of gallstones.

Until recently, cholecystectomy was the only treatment available for symptomatic gallstone disease. During the past 20 years, better understanding of the pathogenesis of cholesterol gallstone disease has led to alternative nonsurgical methods for treating gallstones in selected groups of patients. Use of 2 naturally occurring bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), was reported in 1972 and 1975, respectively, for successful dissolution of cholesterol gallstones in humans. Both these bile acids act by reducing cholesterol secretion in bile, thus enabling it to solubilise more cholesterol from the stone surface. Micellar solubilisation is involved, together with liquid crystal formation in the case of UDCA. Having been extensively studied in clinical trials to assess efficacy and safety, both these compounds are now available for general use. The efficacy of CDCA can be enhanced by single bedtime dose administration and by taking a low cholesterol diet. Bedtime administration also enhances the effect of a suboptimal dose of UDCA. CDCA induces dose-related diarrhoea and hypertransaminaemia, and UDCA can induce calcification of gallstones, thus rendering them resistant to medical dissolution. A combination of the 2 bile acids at half the recommended dose for each has become an accepted practice for reducing adverse effects, and this may also enhance efficacy. One of the main problems of bile acid therapy is that dissolution of gallstones is a very slow process. Use of extracorporeal shockwave lithotripsy (ESWL) to break the stones into smaller fragments, with concurrent use of bile acids, has been shown to speed dissolution rate and to achieve complete gallstone dissolution in 78% of selected cases within 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Chenodeoxycholic Acid↗
PubMed1986

Gallstone recurrence after medical dissolution. An overestimated threat?

We assessed gallstone recurrence rate in 42 patients diagnosed as having complete gallstone dissolution on bile acid therapy. By contrast with most previous studies, this diagnosis was based on ultrasound as well as on radiology, and only patients having their first gallstone recurrence were included in the study. Patients were followed for periods varying from 6 months to 7 years (median 30 months). Eleven patients had recurrences, giving an overall recurrence rate of 26%. A life analysis table was constructed by an actuarial method to compensate for the different lengths of follow-up in individual patients. Corrected recurrence rates by life table analysis were 15%, 21%, 25%, 36%, 45%, 45% and 45% at 1, 2, 3, 4, 5, 6 and 7 years respectively; for the same time intervals, cumulative recurrence rate overestimated the risk of gallstone recurrence (14%, 22%, 31%, 50%, 61%, 79% and 92%). We conclude that previous figures for recurrence rate have been an overestimate; but recurrence rate remains substantial over the first 5 years, and then levels off.

Actuarial Analysis↗
PubMed1985

Quantification of temocillin biliary excretion and gallbladder bile concentration in healthy subjects.

The techniques of duodenal perfusion with polyethylene glycol as a nonabsorbable marker, and cholescintiscan using 99Tc HIDA as a gallbladder bile marker, were used to measure the total duodenal output and gallbladder bile concentration of temocillin after administration of an intravenous bolus injection to each of 6 healthy subjects. We carried out 8 studies. 3 with 0.5g temocillin and 5 with 1g temocillin. The plasma half-life of temocillin was 177 (+/- 25) minutes [mean (+/- SD)] and 196 (+/- 29) minutes with the 0.5g and 1g doses, respectively. Urinary excretion accounted for 38% of the total dose given during the study period of 6 hours, and total biliary excretion was recorded as 2.2% of the given dose for both doses. The mean concentration of temocillin in gallbladder bile was 314.7 (+/- 273.2) mg/L after the 0.5g dose and 474.5 (+/- 307.3) mg/L after 1g dose. It was concluded that temocillin is highly concentrated in the normal gallbladder in man.

Adult↗
PubMed1985

Nutritional assessment in patients with chronic gastrointestinal symptoms: comparison of functional and organic disorders.

We assessed the nutritional status of 119 patients with chronic gastrointestinal symptoms due to organic disorders (inflammatory bowel disease, IBD; peptic ulcer, PU; malabsorption syndrome, M; and malignant gastrointestinal tumours, T), by standard anthropometry and marker proteins (albumin; retinol-binding protein, RBP; and thyroxine-binding prealbumin, TBPA). We also studied 31 patients with irritable bowel syndrome (IBS) and 75 age-matched healthy controls (C). Compared with healthy controls, patients with organic bowel disease had significant abnormality of two or more anthropometric measurements (P less than 0.05). Plasma albumin was reduced in patients with IBD, M and T (P less than 0.001), but RBP and TBPA measurements were lower in all patient categories (P less than 0.01) including IBS. Stepwise discriminant analysis of the patient data alone, using three to six parameters, correctly separated 65 per cent PU patients, 66 per cent IBD and M, 72 per cent IBS and 88 per cent patients with T from other disease categories. We conclude that patients with chronic gastrointestinal symptoms often have some nutritional disturbances and that simple anthropometric and protein measurements might help us to distinguish patients with functional bowel disease from those with organic bowel disease.

Adolescent↗
PubMed1984

Gallbladder abnormalities in acute infectious hepatitis. A prospective study.

We have studied the gallbladder and its contents by ultrasonography in 31 patients with acute viral hepatitis and 23 age-matched controls. Liver cell necrosis was assessed by raised transaminase levels within 24-48 hr of ultrasonography in all patients. Gallbladder wall (GBW) measured 5.16 +/- 0.4 mm (mean +/- SEM) in patients and 2.0 +/- 0.06 mm in controls (P less than 0.001). GBW was thickened (greater than 3 mm) in 21 patients (68%), with double wall appearance in 5 (16%), and sludge was seen in the gallbladder cavity in 7 (23%). GBW thickness was significantly related to serum albumin (r = -0.45, P less than 0.01) and bilirubin (r = 0.50, P less than 0.004), but not to the serum transaminase levels. On repeat measurements after recovery in 13 patients, GBW thickness fell from 5.84 +/- 0.49 mm during acute hepatitis to 2.46 +/- 0.21 mm (P less than 0.001).

Acute Disease↗
PubMed1983

Factors affecting gall-stone dissolution rate during chenic acid therapy.

Gall-stone dissolution rate was measured in 52 patients with radiolucent gall stones in a functioning gall bladder receiving chenic acid 15 mg/kg/day. Percentage reduction in gall-stone area at six months was inversely related to initial gall-stone diameter (n = 52; r = -0.53; p less than 0.001), and to cholesterol saturation index of fasting gall-bladder bile during treatment (n = 28; r = -0.61; p less than 0.001). The duration of treatment required for complete dissolution was directly related to initial gall-stone diameter (r = 0.47; p less than 0.02). We conclude that the rate of gall-stone dissolution depends not only on gall-stone size but also on the degree of unsaturation of gall-bladder bile achieved during chenic acid treatment.

Adolescent↗
PubMed1983

Subclinical protein malnutrition in irritable bowel syndrome: assessment by retinol-binding protein (RBP) and thyroxine-binding pre-albumin (TBPA).

We have assessed the nutritional status of 31 patients with irritable bowel syndrome (IBS) and 75 control subjects by anthropometry (height, weight, mid-arm circumference, biceps, triceps and subscapular skinfolds) and three plasma proteins: albumin, retinol-binding protein (RBP), and thyroxine-binding pre-albumin (TBPA). There was no significant difference between the patients and controls for any of the anthropometric measurements, but mean (+/- s.d.) plasma concentrations of RBP and TBPA were significantly lower in patients with IBS, 7.21 +/- 2.77 mg/dl (P less than 0.01); and 26.57 +/- 7.33 mg/dl, (P less than 0.001) respectively than in the control group, 8.85 +/- 2.56 mg/dl and 32.71 +/- 6.30 mg/dl. We conclude that patients with IBS may have subclinical protein deficiency in the absence of demonstrable organic bowel disease.

Adult↗
PubMed1982

Duodenal intubation as a source of typhoid fever.

Typhoid fever developed in three patients during a period of 13 weeks. Although each of these patients was admitted to a different London hospital, the patients became ill approximately 10 days after undergoing duodenal intubation in one gastroenterology unit. All other patients who had undergone duodenal intubation in the unit during that period of time were investigated. Salmonella typhi was isolated from bile and feces of two out of the 20 other patients (carriers). In each of the three patients who developed typhoid fever, intubation followed within two days of intubation of one of the carriers. After use in each patient, the polyvinyl tubes had been thoroughly washed with disinfectant and detergent. There were no further cases of typhoid fever when a new tube was used for each patient.

Adolescent↗
PubMed1982

Gallstone dissolution rate during chenic acid therapy. Effect of bedtime administration plus low cholesterol diet.

We have studied the dissolution rate of radiolucent gallstones from validated measurements of gallstone area derived from standardized oral cholecystography in 48 patients receiving chenodeoxycholic (chenic) acid, 15 mg/kg/day. Patients were matched in pairs according to gallstone size and randomly allocated to one of two treatment groups. Group A was given chenic acid in three divided doses at mealtimes with an unrestricted diet (the conventional regimen), and group B was given bedtime chenic acid with a low cholesterol diet. In the 24 matched pairs, the mean reduction in gallstone area at 6 months on regimen A was 36% and on B 60%. Median reductions in area were 20% and 57%, respectively (P less than 0.02). Of these matched pairs, 20 were followed at 6 month intervals for 42 months. There was a significant correlation between percentage reduction in gallstone area at 6 months and length of treatment necessary for complete dissolution (P less than 0.001). Fifty percent achieved complete dissolution by 30 months on regimen A, and by 12 months on regimen B (NS). We conclude that gallstone dissolution rate during chenic acid treatment is approximately doubled by bedtime administration plus a low cholesterol diet, thus reducing the duration and cost of treatment.

Chenodeoxycholic Acid↗
PubMed1982

Biliary excretion of amoxycillin and ceftriaxone after intravenous administration in man.

1 Plasma and biliary concentrations of amoxycillin and ceftriaxone were measured after bolus intravenous administration (500 mg) in four subjects with normal hepato-biliary and renal function. 2 The mean plasma elimination half-life for ceftriaxone (t 1/2 = 330 +/- 30 min) was considerably longer than that for amoxycillin (t 1/2 = 60 +/- 9 min). 3 The biliary concentration of ceftriaxone was above plasma concentration of the drug throughout the study period, whereas amoxycillin concentration in the bile was lower than that in plasma. 4 Both plasma and biliary concentrations of ceftriaxone were substantially higher than previously determined minimum inhibitory concentration (MIC) values for E. coli (and several other common biliary tract pathogens) for over 6 h following drug administration. Amoxycillin concentration in plasma fell below MIC by 2 h, and did not reach inhibitory concentrations in bile.

Adult↗
PubMed1982

Minimum effective dose of chenic acid for gallstone patients: reduction with bedtime administration and low cholesterol diet.

The aim of this study was to determine whether bedtime administration and a low cholesterol diet reduce the minimum effective dose of chenodeoxycholic (chenic) acid, defined as the dose giving a mean cholesterol saturation index of 0.8. Dose response studies were carried out in 10 patients with radiolucent gallstones in a functioning gallbladder during three different treatment regimens. On each regimen, all patients received three different doses of chenodeoxycholic acid in random order for one month each. Bedtime chenic acid plus a low cholesterol diet gave the greatest reduction in saturation index. A significant dose/response relationship was found on each regimen. On the conventional regimen of mealtime chenic acid, the minimum effective dose was 14 mg/kg/day; on bedtime chenic acid it was 12.4 mg/kg/day; and on bedtime chenic acid plus low cholesterol diet it was further reduced to 8.4 mg/kg/day (p less than 0.01). There was a dose-related increase in bowel frequency, which was absent at 10.6 mg/kg/day and below. We conclude that administration of chenic acid at bedtime with a low cholesterol diet enables the minimum effective dose for gallstone dissolution to be approximately halved, thus preventing diarrhoea and reducing the cost of treatment.

Adult↗
PubMed1980

Postprandial gall-bladder emptying in patients with gall stones.

Gall-bladder emptying in response to a standard meal was assessed in 34 patients with radiolucent gall stones and 34 matched controls. Percentage gall-bladder emptying, derived from volume measurements made on standardised oral cholecystography, was significantly higher at 15 minutes in the patients than the controls (mean +/- SE of mean 38.0 +/- 3.7% v 28.0 +/- 3.8%). This difference was maintained at 30 and 60 minutes. It is concluded that postprandial gall-bladder emptying is increased in patients with cholesterol gall stones, and that this may be the cause of the small bile-acid pool found in these patients.

Cholelithiasis↗
PubMed1980

Gall-bladder sensitivity to cholecystokinin in patients with gall stones.

Gall-bladder sensitivity to cholecystokinin (CCK) was determined by dynamic cholescintigraphy in 18 patients with radiolucent gall stones and 18 matched controls during an infusion of CCK in which the rate of infusion was increased. In 10 of the matched pairs the patient was more sensitive than the control, in one the control was more sensitive, and in seven no difference was detected (p = 0.012). It is concluded that patients with cholesterol gall stones have increased gall-bladder sensitivity to CCK, and that this may be important in the pathogenesis of this disease.

Cholecystokinin↗
PubMed1979

Optimal timing of doses of chenic acid in patients with gall stones.

Sixteen patients with gall stones were treated with chenic acid (14-16 mg/kg/day) given at three different times in random order for one month each. Before treatment the mean (+/- SE of mean) cholesterol saturation index (SI) of fasting gall-bladder bile was 1.28 +/- 0.06. During bedtime administration of chenic acid the mean SI fell to 0.78 +/- 0.04, which was significantly lower than that obtained with administration in the morning (0.92 +/- 0.05) or with three divided doses at mealtimes (0.92 +/- 0.04). The bile remained supersaturated in seven patients when they received a single morning dose, in five patients when they received mealtime doses, but in only one patient when a single bedtime dose was given. There was no significant difference in side effects between the three different dose timings, or in the proportion of bile acids present in the bile as chenic acid. This enhanced effect obtained with bedtime administration may be due to the enterohepatic circulation of bile acids being maintained during overnight fasting.

Adult↗
PubMed1979

Intestinal bacterial metabolism of protein and bile acids: role in pathogenesis of hepatic disease after jejuno-ileal bypass surgery.

Jejunal bacterial colonization and intestinal metabolism of bile acids and protein by bacteria have been investigated in 12 patients with abnormal liver histology following jeujno-ileal bypass surgery for obesity. Aerobic and/or anaerobic colonic flora was present in jejunal aspirates from 8 of 12 bypass patients, but in none of the controls. Intestinal protein metabolism and bile acid deconjugation (measured by urinary indican excretion and 14C-glycocholic acid breath test) was significantly enhanced in bypass patients. Intestinal bacterial overgrowth, with abnormal intestinal metabolism by bacteria of ingested nutrients and bile acids, could contribute to hepatic disease after bypass surgery via the production of endogenous hepatotoxins.

Adult↗
PubMed1979

Cimetidine: effect on pancreatic and biliary function in man.

1 Pancreatic and biliary function were studied in eight patients taking oral cimetidine (1.6 g/day for 6 weeks) for endoscopically confirmed active peptic ulcer disease. 2 Postprandial jejunal tryptic activity and bile acid concentration were unchanged during cimetidine given for 1 and 6 weeks. 3 Postprandial gallbladder emptying was also unchanged. 4 Direct examination of postprandial upper jejunal aspirate for deconjugated bile acids was negative in all patients; but the more sensitive [14C]-glycocholate bile acid breath test showed a significant increase in breath 14CO2, indicating increased bacterial deconjugation of bile acids in the gastrointestinal tract.

Adult↗