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C O Record

Publications and source records attributed to C O Record.

At least 55 records · Page 3Linked to original sources

Normal splanchnic but impaired peripheral insulin-stimulated glucose uptake in cirrhosis.

The site of impaired glucose uptake in cirrhosis is uncertain. We therefore performed hyperglycemic clamps (glucose 10 mmol/L) in 10 patients with compensated alcoholic cirrhosis and impaired glucose tolerance and in six control subjects. Muscle glucose uptake was estimated in patients and controls with the forearm technique. In the cirrhotic subjects splanchnic glucose uptake was measured with hepatic vein catheterization and primed continuous infusions of indocyanine green and [6-3H]glucose. To assess insulin-independent glucose uptake and the effects of elevated nonesterified fatty acid levels on glucose uptake, we repeated the study with somatostatin to induce insulin deficiency and a nicotinic acid analog, acipimox, to inhibit lipolysis. Substrate disposal was assessed on indirect calorimetry. Despite similar stimulated insulin levels, total glucose utilization was lower in the cirrhotic subjects (3.9 +/- 0.3 vs. 8.8 +/- 1.7 mg/kg/min, p = 0.006). This deficiency was accounted for by lower nonoxidative glucose disposal (1.2 +/- 0.2 vs. 5.8 +/- 1.6 mg/kg/min, p = 0.002). Forearm glucose uptake was lower in the cirrhotic subjects (0.39 +/- 0.06 vs. 1.21 +/- 0.3 mg/100 ml/min, p = 0.001). However, splanchnic glucose uptake at 1.59 +/- 0.14 mg/kg/min was similar to that reported in other studies of normal subjects. Insulin-independent glucose uptake was normal, and acipimox had no effect on total or forearm glucose utilization. Glucose intolerance in cirrhosis is characterized by impaired peripheral insulin-stimulated non-oxidative glucose disposal. The high nonesterified fatty acid levels seen in cirrhosis most likely do not contribute to this defect. Splanchnic glucose uptake is normal in cirrhosis.

Adult↗

A method of enhancing verocytotoxin production by Escherichia coli.

The number of verocytotoxin producing Escherichia coli (VTEC) present in the faeces during an infection may be very low, making their detection difficult. We report a method for enhancing toxin production by VTEC using mitomycin C as an inducing agent with the aim of improving the detection of VTEC. In pure culture, mitomycin C enhanced toxin production up to 100-fold. When applied to mixed faecal culture, toxin could be detected in mitomycin C treated samples when standard cultures were negative and when substantially fewer verocytotoxin-producing bacteria were present. Use of this method may aid in the detection of VTEC and is appropriate for use in the routine diagnostic laboratory.

Animals↗

Limitations of laser treatment for malignant dysphagia.

Of 86 patients with inoperable malignant dysphagia, 68 (79 per cent) underwent successful palliation by endoscopic laser therapy, of whom 24 remained well palliated until the time of death. In 18 patients laser treatment was unsuccessful and nine of these underwent intubation, eight successfully. After successful laser therapy, dysphagia recurred in 44 patients a mean of 7.8 weeks later. Of these, 31 received palliation until death by dilatation with or without laser therapy, and 13 required intubation. The overall laser-related complication rate was 12 per cent with a mortality rate of 4 per cent. The intubation-related mortality rate was 9 per cent.

Adenocarcinoma↗

Effect of acute inhibition of lipolysis on operation of the glucose-fatty acid cycle in hepatic cirrhosis.

Hepatic cirrhosis is frequently associated with glucose intolerance and insulin resistance, but the mechanisms underlying the insulin insensitivity are unknown. Plasma concentrations of nonesterified fatty acids (NEFA) are typically elevated in cirrhosis, and the glucose-fatty acid cycle provides a mechanism by which fatty acids may play a role in regulating glucose metabolism. We have therefore investigated the effect of acute inhibition of lipolysis, using the nicotinic acid analogue, acipimox, in 10 male patients with cirrhosis. All subjects were studied in the postabsorptive state after a 10- to 12-hour fast and were given either acipimox 250 mg or a placebo orally 2 hours before a 75-g oral glucose tolerance test (OGTT) and an infusion of insulin (50 mU/kg/h) and glucose (6 mg/kg/min) (insulin sensitivity tests [IST]). The drug was taken in a double-blind crossover design for each test. During the 2 hours following acipimox, there were rapid decreases in plasma NEFA, glycerol, and 3-hydroxybutyrate, confirming inhibition of lipolysis, while there were significant decreases in glucose, insulin, and C-peptide (P less than .001) compared with patients receiving the placebo. Acipimox blunted the increase in glucose after oral glucose loading and decreased incremental glucose concentration (from 579 +/- 76 to 445 +/- 65 mmol/min/L, P less than .02) and incremental insulin concentration (from 13.4 +/- 2.5 to 9.0 +/- 1.4 U/min/L, P = .056) in the OGTT. Improvements in classification of glucose tolerance were seen in five subjects. During the IST, significant reductions occurred in steady-state blood glucose (to 8.8 +/- 1 mmol/L, P less than .02) and C-peptide (to 3.0 +/- 0.5 nmol/L, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results.

The results of a 3-year, placebo-controlled trial of prednisolone treatment in primary biliary cirrhosis (PBC) are presented. The active (n = 19) and placebo (n = 17) arms were initially well matched for age, menopausal status and disease severity. At 3 years hepatic symptoms were relatively improved in the prednisolone group. Hepatic mortality was 3/19 (prednisolone), 5/17 (placebo) (p = n.s.). For all liver blood tests the trend favoured prednisolone treatment, though the differences were only significant for alkaline phosphatase and protein. All immunoglobulins fell significantly. Quantitative ELISA determination of antimitochondrial antibody showed a significant fall in the prednisolone group compared with placebo (p less than 0.001 at 1 year, p less than 0.05 at 3 years). Deterioration in histology (appearance of cirrhosis) was more common in the placebo group. Overall hepatic function (hepatic mortality, doubling in bilirubin, 6 milligrams fall in albumin, de novo appearance of cirrhosis or symptoms of portal hypertension) was significantly worse in the placebo group (p less than 0.01). After 3 years no significant differences could be detected in bone mineral content (single photon absorptiometry of radius and femur) between the two groups or in comparison with other PBC patients. Thus, after 3 years, prednisolone treatment was associated with a better overall hepatic outcome and little evidence of increased bone loss.

Absorptiometry, Photon↗

Morphometric studies in duodenal biopsies from patients with coeliac disease: the effect of the steroid fluticasone propionate.

Morphometric measurements have been performed on small intestinal biopsy specimens from patients with untreated coeliac disease before and after six weeks oral treatment with a steroid of low systemic bioavailability (fluticasone propionate). Measurements were obtained by point counting and also by a computer-aided measuring system with reference to a constant area of the muscularis mucosa. Fluticasone propionate led to a parallel reduction in the intraepithelial lymphocyte count within the surface (P less than 0.001) and crypt epithelium (P less than 0.01). The intra-epithelial lymphocyte count assessed by reference to constant areas of the muscularis mucosa and surface epithelium were decreased two-fold (P less than 0.01) and seven-fold (P less than 0.001) respectively. Fluticasone propionate treatment also led to significant increases in the absorptive surface epithelium as shown by an increase in the villus:crypt ratio (P less than 0.01), the epithelial cell height (P less than 0.01) and two- to three-fold increases in the area and length of the surface epithelium (P less than 0.001). Short-term fluticasone propionate treatment appears to exert a powerful beneficial effect upon duodenal morphology in patients with coeliac disease. Whether the alterations seen are comparable to a similar period of gluten withdrawal is not yet known.

Adult↗

Is topical therapy necessary in acute distal colitis? Double-blind comparison of high-dose oral mesalazine versus steroid enemas in the treatment of active distal ulcerative colitis.

Thirty-seven patients suffering an attack of acute distal ulcerative colitis of mild or moderate severity were randomized in a double-blind, double-dummy fashion to receive either 800 mg oral mesalazine four times daily (18 patients) or steroid enemas twice daily (19 patients) for 4 weeks. Both treatments were well tolerated with no adverse effects. Three patients in each group were withdrawn because of clinical deterioration but both treatments produced significant clinical improvement with decreases in stool frequency and scores for urgency, bleeding and tenesmus. There were no significant differences between the treatments although there was a slight trend in favour of the enemas for reduction in rectal bleeding. Activity of the colitis as graded at sigmoidoscopy also decreased significantly with both treatments and there were corresponding improvements in histological parameters of inflammatory activity assessed with the aid of a computerized morphometric system. Little correlation was seen between clinical, sigmoidoscopic and histological changes.

Acute Disease↗

Morphometric studies in rectal biopsy specimens from patients with ulcerative colitis: effect of oral 5 amino salicylic acid and rectal prednisolone treatment.

Morphometric measurements were performed on rectal biopsy specimens from 10 normal control subjects and 33 patients with a relapse of distal ulcerative colitis before and after treatment for four weeks in a double blind controlled trial with oral eudragit S coated 5 amino salicylic acid (n = 12) or rectal prednisolone enemas (n = 15). Measurements were assessed using a computer aided measuring system and a counting technique. When untreated patients were compared with the control group there were significant decreases in the area and height of the surface epithelium, in the area of crypt epithelium, and in the ratios of goblet cells to epithelial cells and of surface epithelium to lamina propria. The vascular and lamina propria areas and the number of intraepithelial polymorphs were increased. Treatment with 5 amino salicylic acid and corticosteroids resulted in similar morphological improvements: there was an increase in the area and height of the surface epithelium and the ratios of surface epithelium to lamina propria and of surface to crypt cell height. The ratio of goblet cells to epithelial cells also increased after treatment, while the numbers of polymorphs in the surface and crypt epithelium and lumen decreased. In conclusion, computerised morphometry is valuable for the assessment of the treatment of patients with ulcerative colitis and that in the doses used both treatments were of similar efficacy.

Aminosalicylic Acids↗

A pilot study of fluticasone propionate in untreated coeliac disease.

Although gluten withdrawal is likely to remain the mainstay of treatment for adult coeliac disease, many patients find the diet inconvenient and unpalatable and compliance among asymptomatic patients is often poor. Oral corticosteroids have been used for patients who seem to be resistant to gluten withdrawal but preparations with low systemic bioavailability might be preferable. We have given a new glucocorticoid (fluticasone propionate) to 12 adults with untreated coeliac disease for six weeks while they were on a normal diet. One patient defaulted and one suffered a relapse in a pre-existing neoplasm. Excluding these, there was an improvement of symptoms, a mean weight gain of 2 kg, and a rise in albumin of 5.4 g/l. There was a significant improvement in the lactulose/mannitol excretion ratio (p less than 0.05) and in all histological variables examined in paired biopsy specimens (surface and crypt intraepithelial lymphocyte/enterocyte and goblet cell/enterocyte ratios and enterocyte height, p less than 0.01 or better). In six paired specimens sucrase and alkaline phosphatase activity increased in all (p less than 0.05) and lactase in five of six. No appreciable side effects were observed, but two patients had suppressed cortisol values and synacthen responses at six weeks. A further three, with normal pretrial results, had a blunted tetracosactrin response at six weeks. Fluticasone propionate seems worthy of further assessment in the treatment of coeliac disease as an adjunct to gluten withdrawal.

Adult↗

Effect of protein and lactulose on the production of gamma-aminobutyric acid by faecal Escherichia coli.

The value of lactulose treatment in hepatic encephalopathy is widely recognised but its mode of action remains controversial. Much evidence supports a role for gamma-aminobutyric acid in hepatic encephalopathy, and lactulose could alter its bacterial production in the gut. Using the rat synaptic membrane assay and gas chromatography mass spectrometry, the production of gamma-aminobutyric acid by faecal Escherichia coli, with and without the addition of albumin, haemoglobin, whole blood, and lactulose under aerobic and anaerobic conditions was determined. Using an inorganic medium, maximal gamma-aminobutyric acid production occurred after a culture period of between 25 and 50 hours. The concentration after 30 hours of aerobic culture at 37 degrees C by a single strain was mean (SEM), 101 (5) mumol/l (99% confidence intervals 87-114 mumol/l; n = 8; interassay coefficient of variation 14.7%). gamma-aminobutyric acid production was significantly increased by the addition of albumin and haemoglobin. Under anerobic conditions, it was one fifth of that produced aerobically, but the addition of albumin and haemoglobin increased production by greater than 700%. Lactulose did not significantly attenuate gamma-aminobutyric acid production under aerobic or anaerobic conditions. gamma-aminobutyric acid determined by the rat synaptic membrane assay showed a highly significant correlation (r = 0.99) with that detected by gas chromatography mass spectrometry. These data confirm that gamma-aminobutyric acid is produced by faecal E coli and that protein enhances its production considerably, and suggest that lactulose does not exert its therapeutic effect by attenuating gamma-aminobutyric acid production.

Aerobiosis↗

Primary and secondary malignant disease of the liver and fulminant hepatic failure.

The association and presentation of malignant disease of the liver with fulminant hepatic failure has been described sporadically, but the absence of a large series has meant that malignancy is rarely considered in the differential diagnosis of such hepatic failure. We describe three cases and review the best documented reports in the literature. Review of 25 patients shows that in most cases, excluding lymphoma, the liver is massively replaced by tumor that often spreads in an intrasinusoidal pattern. The diffuse nature of malignant spread results in a relative failure of diagnostic imaging and thus the diagnosis is frequently made after death, which occurs a mean 7.8 days after hospital admission. Review of the clinical features and investigations in these cases shows that, when hepatomegaly and ascites are present in middle-aged or older patients at the time of admission, malignancy should be considered as the cause. Why the liver should be massively replaced in such patients remains obscure.

Adult↗

A pilot, double-blind, controlled 1-year trial of prednisolone treatment in primary biliary cirrhosis: hepatic improvement but greater bone loss.

A randomized, double-blind, 1-year pilot study of prednisolone treatment for primary biliary cirrhosis was undertaken. Nineteen patients received 30 mg prednisolone per day initially, with a maintenance dose of 10 mg per day. Seventeen patients received placebo. The groups were matched for age, menopausal status, hepatic histological stage and bilirubin. Treatment was well tolerated without dropouts. Two patients receiving prednisolone developed diabetes, one a duodenal ulcer and one depression. One patient receiving placebo died for liver failure after 3 months. Cholestatic symptoms (itch and fatigue) improved on prednisolone. There was significant (prednisolone vs. placebo) improvement in transaminase (p = 0.0214), alkaline phosphatase (p = 0.0032), procollagen III peptide (p = 0.0103), immunoglobulin G (p = 0.0012) and liver histology (p = 0.016); these changes were greatest among noncirrhotic patients. No patient developed skeletal symptoms. Fifty-seven per cent had abnormal triolein breath tests prior to treatment, and 65% had abnormally low calcium absorption tests. Calcium absorption increased significantly in the treated group vs. placebo at 2 weeks (p less than 0.02), but not at 1 year. Femoral photon absorptiometry fell in the prednisolone group after 1 year (-3.5% vs. placebo +0.5%, p less than 0.05), as did trabecular bone volume (-6% vs. -2.8%, p less than 0.005) and resorption surface (-11% vs. +2%, p less than 0.02) on serial bone biopsy. Prednisolone seems to exert a favorable hepatic effect in primary biliary cirrhosis but at the expense of increased bone loss to approximately twice the expected rate. Prednisolone treatment merits further assessment in primary biliary cirrhosis over a longer period, with attention to selection of patients most likely to benefit and continuing observation of bone mass to better establish the "cost/benefit" ratio.

Adult↗

Placebo-controlled trial of terlipressin (glypressin) in the management of acute variceal bleeding.

In a double-blind trial 60% of acute variceal bleeding episodes were controlled with terlipressin (glypressin) compared with 37% in patients given placebo (NS). Rebleeding was more common in the placebo group so that at 5 days bleeding remained under control in 54% of patients treated with terlipressin compared with only 19% after placebo therapy (p less than 0.025). Blood transfusion requirements were similar in the two groups. Terlipressin appeared to be the most effective in those patients with severe hepatic dysfunction.

Acute Disease↗

Is a persistent adenovirus infection involved in coeliac disease?

Recent evidence has implicated adenovirus 12 in the aetiology of coeliac disease so that persistent infection by this virus must be considered. We have undertaken a search for adenovirus DNA in duodenal biopsy samples from a total of 26 coeliac and non-coeliac patients. We could find no evidence of persistent virus DNA by Southern blot techniques even under conditions which approach a sensitivity of one copy of virus genome per cell, and use either adenovirus 12 or 41 DNA.

Adenoviridae Infections↗