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N McIntyre

Publications and source records attributed to N McIntyre.

At least 55 records · Page 3Linked to original sources
PubMed1993

A comparison of transjugular and plugged-percutaneous liver biopsy in patients with impaired coagulation.

Patients with liver disease frequently have impaired blood coagulation. The optimal method for liver biopsy in this situation is not established. To investigate this issue we randomised 117 patients with impaired blood coagulation, in whom liver biopsy was required, to receive either transjugular or plugged-percutaneous biopsy. Seventeen patients were excluded prior to biopsy and a protocol biopsy was performed in 100 patients (44 transjugular, 56 plugged-percutaneous). Liver tissue was obtained in 97 (42 transjugular, 55 plugged-percutaneous). Plugged-percutaneous liver biopsy was quicker and easier than transjugular liver biopsy and the biopsies obtained were significantly larger (12 +/- 5 mm vs. 6 +/- 4 mm; p < 0.001). However, 2 of 56 (3.5%) patients who received plugged-percutaneous biopsy had haemorrhage which required transfusion, while none of the 44 patients who received transjugular biopsy had haemorrhage (not significant). Both methods of liver biopsy were associated with a high success rate and a low incidence of complications. Plugged-percutaneous liver biopsy provides larger biopsies but may be associated with an increased risk of haemorrhage.

Biopsy↗
PubMed1993

Energy expenditure and substrate metabolism after oral fructose in patients with cirrhosis.

There is little information on the metabolic response to ingested fructose in patients with cirrhosis. Glucose kinetics, plasma lipid and blood lactate levels, whole body substrate oxidation rates and energy expenditure were measured following ingestion of 75 g fructose, in 8 cirrhotic patients and 6 controls. Fasting plasma glucose levels and rates of glucose appearance (Ra) and disappearance (Rd) were similar. The basal rate of lipolysis was higher in cirrhotic patients (P < 0.05), but whole body lipid and carbohydrate oxidation rates and energy expenditure were similar. After fructose ingestion, plasma fructose levels were much higher in cirrhotic patients (P < 0.001) and the incremental area under the plasma glucose curve was twice that of controls (P < 0.05). The increase in glucose in patients with cirrhosis was due to an increase in glucose Ra and an initial reduction in glucose Rd. Plasma non-esterified fatty acid levels fell to similar low levels in both groups. Glycerol levels fell in controls (P < 0.05) but not in cirrhotic patients. Blood lactate levels, fasting and after oral fructose, were similar in cirrhotics and controls. The time course of suppression of lipid oxidation and stimulation of carbohydrate oxidation was more closely related to fructose levels than to serum fatty acid levels in both groups. The percent suppression and total quantity of lipid oxidized in 4 h after fructose were not significantly different, but the suppressed lipid oxidation rates and elevated carbohydrate oxidation rates were sustained for longer in the cirrhotics. The data suggest that fructose uptake and metabolism inhibits oxidation of intracellular lipid. There was a smaller increase in energy expenditure after fructose in cirrhotics (P < 0.001), but normal overall storage of fructose; the likely explanation is reduced first pass hepatic fructose uptake in cirrhotics making more fructose available to the periphery for incorporation into muscle glycogen. The energy cost of storing fructose as muscle glycogen is less than that of storing it as liver glycogen. Preferential incorporation of fructose carbon into muscle glycogen, with lower rates of hepatic glycogen and triglyceride synthesis, would therefore result in less energy expenditure after a fructose load in cirrhotics.

Administration, Oral↗
PubMed1993

Liver/spleen scintigraphy for diagnosis of splenic infarction in cirrhotic patients.

Splenic infarction is rare in cirrhotic patients. The diagnosis of the condition is based on clinical findings and splenic imaging. In recent years, ultrasonography and computed tomographic scan have gained popularity over the more classical scintigraphy as the preferred investigations for the diagnosis of splenic infarction. We report three cases of splenic infarction in patients with cirrhosis and portal hypertension. Computed tomographic scan, angiography and ultrasonography failed to identify the lesions and the diagnoses were finally made with the aid of liver--spleen scintigraphy. We suggest that scintigraphy is the investigation of choice if splenic infarction is suspected in patients with congestive splenomegaly secondary to liver cirrhosis.

Adult↗
PubMed1993

Metabolic handling of orally administered glucose in cirrhosis.

We used a dual-isotope method (oral [1-14C]glucose and intravenous [6-3H]glucose) to examine whether the oral glucose intolerance of cirrhosis is due to (a) a greater input of glucose into the systemic circulation (owing to a lower first-pass hepatic uptake of ingested glucose, or to impaired inhibition of hepatic glucose output), (b) a lower rate of glucose removal, or (c) a combination of these mechanisms. Indirect calorimetry was used to measure oxidative and nonoxidative metabolism. Basal plasma glucose levels (cirrhotics, 5.6 +/- 0.4[SE], controls, 5.1 +/- 0.2 mmol/liter), and rates of glucose appearance (Ra) and disappearance (Rd) were similar in the two groups. After 75 g of oral glucose, plasma glucose levels were higher in cirrhotics than controls, the curves diverging for 80 min despite markedly higher insulin levels in cirrhotics. During the first 20 min, there was very little change in glucose Rd and the greater initial increase in plasma glucose in cirrhotics resulted from a higher Ra of ingested [1-14C]glucose into the systemic circulation, suggesting a reduced first-pass hepatic uptake of portal venous glucose. The continuing divergence of the plasma glucose curves was due to a lower glucose Rd between 30 and 80 min (cirrhotics 236 +/- 17 mg/kg in 50 min, controls 280 +/- 17 mg/kg in 50 min, P < 0.05, one-tailed test). Glucose metabolic clearance rate rose more slowly in cirrhotics and was significantly lower than in controls during the first 2 h after glucose ingestion (2.24 +/- 0.17 vs 3.30 +/- 0.23 ml/kg per min, P < 0.005), in keeping with their known insulin insensitivity. Despite the higher initial glucose Ra in cirrhotics, during the entire 4-h period the quantity of total glucose and of ingested glucose (cirrhotics 54 +/- 2 g [72% of oral load], controls 54 +/- 3 g) appearing in the systemic circulation were similar. Overall glucose Rd (cirrhotics 72.5 +/- 3.8 g/4 h, controls 77.2 +/- 2.2 g/4h) and percent suppression of hepatic glucose output over 4 h (cirrhotics, 53 +/- 10%, controls 49 +/- 8%) were also similar. After glucose ingestion much of the extra glucose utilized was oxidized to provide energy that in the basal state was derived from lipid fuels. Glucose oxidation after glucose ingestion was similar in both groups and accounted for approximately two-thirds of glucose Rd. The reduction in overall nonoxidative glucose disposal did not reach significance (21 +/- 5 vs. 29 +/- 3 g/4 h, 0.05 < P < 0.1). Although our data would be compatible with an impairment of tissue glycogen deposition after oral glucose, glucose storage as glycogen probably plays a small part part in overall glucose disposal. Our results suggest that the higher glucose levels seen in cirrhotics after oral glucose are due initially to an increase in the amount of ingested glucose appearing in the systemic circulation, and subsequently to an impairment in glucose uptake by tissues due to insulin insensitivity. Impaired suppression of hepatic glucose output does not contribute to oral glucose intolerance.

Administration, Oral↗
PubMed1993

Clinical, biochemical and histological features in 102 patients with chronic hepatitis C virus infection.

The clinical, biochemical and histological features of 102 consecutively referred patients with chronic hepatitis C virus infection were analysed. Demographic, epidemiological, biochemical, haematological and histological details were catalogued for each patient. The mean follow-up was 49 +/- 6 months. Liver biopsies were obtained from 92 patients; a second biopsy was obtained from 35 patients. The average known duration of infection was 8.6 +/- 0.7 years. The most common risk factors that could be identified were past blood transfusion, surgery or intravenous drug abuse. Twenty-four of the 27 patients (85%) with past blood transfusion had received blood in countries outside of northern Europe. In contrast, 12 of the 16 former drug users were northern European. Patients were frequently diagnosed incidentally; one-quarter had no symptoms of liver disease and were generally asymptomatic or had presented with non-specific complaints and were found to have abnormal serum aminotransferase levels after routine screening. The mean serum aminotransferase levels were not significantly different in those presenting with fatigue compared to those diagnosed incidentally. The most common physical sign in these patients was a palpable liver, which was present in 52%. The mean serum albumin concentration in patients older than 40 years was significantly lower than that in younger patients. Splenomegaly and endoscopic evidence of varices was also more common in older patients. Cirrhosis was present in 37% of patients at presentation: 20% showed progression on rebiopsy, and 5% developed cirrhosis within 4 years of initial presentation. Of those treated, 27% showed histological improvement. Histological severity did not correlate with duration of disease, but did correlate with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Clinicopathological investigation of primary, uncomplicated maedi-visna virus infection.

Maedi-visna virus infection in a flock of sheep in Scotland was associated with respiratory disease, neurological disease, mastitis and lameness. The major clinical signs were dyspnoea (particularly on exercise), progressive fore- and hindlimb ataxia and balance defects, mammary induration and multilimb lameness, occasionally with enlarged carpal joints. Pathological examinations revealed lesions in the lungs, central nervous system, mammary glands and joints which were consistent with those induced by maedi-visna virus. The was no clinical or pathological evidence of concurrent sheep pulmonary adenomatosis, and pulmonary bacterial infections, when they occurred, were superimposed on the lesions due to maedi-visna virus.

Animals↗
PubMed1992

Genetic diagnosis of Gaucher's disease.

The inherited disorder Gaucher's disease can be caused by various mutations in the glucocerebrosidase gene. Some mutations may be associated with greater severity, and there is a need for methods of gene analysis that would facilitate screening and diagnosis. We have studied the molecular basis of Gaucher's disease in twelve unrelated patients of diverse ethnic origin by means of the amplification refractory mutation system (ARMS). Primers for the polymerase chain reaction were designed to discriminate between mutant and wild-type alleles of glucocerebrosidase and to allow separation from products of the related pseudogene. The nucleotide 1226 mutation (asparagine 370----serine) and 84GG (an insertional frameshift mutation) were found exclusively in five patients of Ashkenazi Jewish descent (7 and 2 of the 10 disease alleles, respectively). Two point mutations, at nucleotides 1448 (leucine 444----proline) and 1504 (arginine 463----cysteine), were found in 4 and 3 alleles, respectively; they were associated with rapidly progressive disease and neurological involvement in non-Jewish patients. The ARMS procedure for direct detection of common mutations in glucocerebrosidase will facilitate genetic counselling and screening programmes for individuals at risk of Gaucher's disease.

Adolescent↗
PubMed1992

Esophageal staple transection as a salvage procedure after failure of acute injection sclerotherapy.

It is not clear which therapy should be used in patients with bleeding esophageal varices that are not controlled by emergency sclerotherapy. This is a high-risk group with reported mortality rates of between 70% and 90%. We report our 7-yr experience with staple transection of the esophagus in this patient group. Of 168 patients (280 bleeding episodes) treated with sclerotherapy, 22 had emergency staple transection for failure to control bleeding. Bleeding was controlled in 20 patients (90%), and 10 patients (45%) survived to leave the hospital, including 4 of 10 patients (40%) with Pugh grade C liver disease. We suggest that emergency staple transection is an effective salvage treatment for this high-risk group.

Emergency Medical Services↗
PubMed1992

Bleeding from staple line erosion after esophageal transection: effect of omeprazole.

Esophageal staple transection effectively controls acute variceal bleeding, but up to 50% of these patients will have recurrent upper gastrointestinal bleeding. In our experience, most of these bleeding episodes are caused by total or partial circumferential ulceration at the level of the staple transection: staple line erosion. It caused rebleeding in 29 (40%) of our patients. Whereas the pathogenesis of this lesion is unknown, acid reflux is a consequence of transection surgery. Assuming that staple line erosion could be healed by acid suppression therapy, thereby preventing recurrent bleeding, an acid suppression regimen was evaluated prospectively in 24 patients. Only six (25%) healed with daily standard (300 mg) or high-dose (1,200 mg) ranitidine combined with sucralfate (4 gm). The remaining 18 (75%) healed after omeprazole administration (40 mg/day) for 1 mo. Maintenance ranitidine alone (300 mg/day) was introduced, but 11 (48%) had relapse of erosions. All 11 healed with omeprazole (40 mg/day) for 2 mo, but again on maintenance ranitidine, 10 relapsed. All healed with further omeprazole and healing persisted with long-term administration (20 mg/day). Fifteen rebleeding episodes occurred in eight patients on maintenance ranitidine. Whereas relapse of staple line erosions did occur in the absence of rebleeding, all rebleeding episodes were associated with the relapse of staple line erosion. Omeprazole is more effective than ranitidine alone and combined with sucralfate in healing staple line erosion. Omeprazole prevents rebleeding, which may enhance the long-term benefits of staple transection for acute variceal bleeding.

Adult↗
PubMed1992

Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.

Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.

Antigens, Viral↗
PubMed1992

Adult "idiopathic" extrahepatic venous thrombosis. Importance of putative "latent" myeloproliferative disorders and comparison with cases with known etiology.

The etiology of extrahepatic venous obstruction (EHVO) is unknown in 50% of cases. Recently the presence of a "latent" myeloproliferative disorder has been reported in adults with "idiopathic" EHVO. We evaluated the course of these patients to establish if any putative latent myeloproliferative disorder influenced the clinical course compared to those with a known cause. Among 132 EHVO patients, 78 (59%) had a known etiology, 7 (5%) with an overt myeloproliferative disorder. The "idiopathic" group had 54 patients; 24 (13 men, 11 women) were diagnosed after 15 years of age, (median 38 years, range 17-70) with a median follow up of 96 months (19-372). Only 2 (8%) developed an overt myeloproliferative disorder. These 24 had a similar pattern of bleeding and onset of ascites as those with known cause. In EHVO failure to diagnose a latent myeloproliferative disorder does not influence the course of variceal bleeding, and thus has little prognostic significance.

Adolescent↗
PubMed1992

The effect of an eucaloric high carbohydrate diet on circulating levels of glucose, fructose and non-esterified fatty acids in patients with cirrhosis.

Twelve cirrhotic patients and six controls were fed an eucaloric high carbohydrate (CHO) diet for 3 days. Fasting serum triglyceride (TG), non-esterified fatty acids (NEFA), glucose, insulin and glycerol were estimated daily. On the 3rd day of the study we measured NEFA, glucose, insulin, and fructose every 45 min from 07:45 h until 19:45 h, and then every 4 h until 07:45 h the next day. The patients were divided into two groups of six on the basis of plasma lecithin-cholesterol acyltransferase (LCAT) activity: group A cirrhotics (with good liver function--LCAT activity: 40.6-65.7 nmol.ml-1.h-1; mean 48.5), and group B (poor liver function--LCAT: 23.7-32.3; mean 27.4). On the high CHO diet there was an increase in the fasting serum TG with a peak after 2 or 3 days. The increase in serum TG in controls was greater (p less than 0.01) than in either group of cirrhotics. In the controls and in group A most of the extra TG was carried in VLDL; in group B only 39% of the TG increment was found in VLDL. Fasting NEFA fell with 3 days of CHO feeding in the control group (p less than 0.01); they were unchanged in group A, and rose in group B to a significantly higher level than in controls (p less than 0.01). During day 3 when a high CHO diet was fed plasma NEFA levels fell in cirrhotics, and for most of the day the mean NEFA concentration in group B patients was significantly (p less than 0.05) lower than in normals. On day 3 glucose and fructose levels rose after each meal--much more in cirrhotics than in controls (and more in group B than in group A), and for most of the day they were significantly higher in group B patients as compared to the controls (glucose p less than 0.01, fructose p less than 0.001). Our results supported the hypothesis that plasma NEFA would be lower following high CHO meals in cirrhotics than in controls. This suggests that a high NEFA utilisation, which occurs in fasting cirrhotics, is not present throughout the day. Following a CHO meal, we suggest that tissues derive energy directly from the dietary sugars which are present in high concentration during the period of absorption and that this reduces the post prandial requirement for NEFA.

Adult↗
PubMed1992

The effects of alcohol use on rebleeding and mortality in patients with alcoholic cirrhosis following variceal haemorrhage.

The effect of continued alcohol intake on prognosis in alcoholic cirrhotics who have already bled from varices is controversial. To investigate the effect of alcohol intake on prognosis we studied 189 consecutive alcoholic cirrhotics admitted, for the first time, to the Royal Free Hospital with variceal bleeding. Sixty-six died within 30 days of admission and 23 were excluded from the study for other reasons. Of the 100 remaining 15 remained 'probably abstinent' over long-term follow-up, 29 drank occasionally and 56 continued to misuse/abuse alcohol. The percentage survival probability at 2 years was 66% in the probable abstainers, 68% in the occasional drinkers and 63% in the alcohol abuse/misuse group. There were no significant differences in either mortality or rebleeding rates between the three groups. A rebleeding index (designed to take account of the number of rebleeds per patient and the total length of follow-up) also failed to show any significant difference between the three groups. The Cox proportional hazard model was used to study the effect of the following factors on rebleeding and mortality; age, sex, alcohol use, Pugh's score, acute treatment received for initial variceal bleed and long-term treatment received for prevention of recurrent variceal haemorrhage. Pugh's score was significantly related to risk of death during follow-up (p = 0.0122), but none of the other factors was significantly related to risk of rebleeding or mortality. Using conventional methods to determine alcohol use we were unable to demonstrate significant effects of alcohol intake on rebleeding or mortality in alcoholic cirrhotics who had bled from oesophageal varices.

Alcohol Drinking↗
PubMed1992

Twenty-four hour C-peptide and insulin secretion rates and diurnal profiles of glucose, lipids and intermediary metabolites in cirrhosis.

1. To examine the contributions of hypersecretion and decreased insulin clearance to the hyperinsulinaemia of cirrhosis, insulin secretion was calculated over the day from serum C-peptide concentrations and C-peptide metabolic clearance rate. The latter was measured during infusions of recombinant human C-peptide. In cirrhotic patients (n = 9) insulin secretion rate was twice that of normal control subjects (n = 10), both in the basal state [02.00-07.00 hours, 15.7 +/- 2.1 (mean +/- SEM) nmol/h (2.6 +/- 0.4 units/h) versus 7.0 +/- 0.9 nmol/h (1.2 +/- 0.2 units/h), P < 0.002] and over 24 h [787 +/- 93 nmol (132 +/- 16 units) versus 346 +/- 34 nmol (58 +/- 6 units), P < 0.001]. However, the area under the serum insulin concentration curve was approximately six times greater in the cirrhotic patients (24 h basal, 6.3 +/- 1.0 versus 1.1 +/- 0.3 nmol l-1 h, P < 0.001; 24 h total, 21.7 +/- 3.2 versus 3.7 +/- 0.7 nmol l-1 h, P < 0.001). Thus, despite impairment of insulin clearance there is continuing hypersecretion of insulin in cirrhosis. 2. The relationship of carbohydrate and lipid metabolism with insulin secretion was assessed. In cirrhotic patients, 24 h blood glucose profiles showed a worsening of glucose tolerance over breakfast, despite greater insulin secretion compared with other meals, suggesting that the insulin insensitivity of cirrhosis is worse at this time. 3. Cirrhotic patients showed impaired suppression of blood glycerol levels after meals but normal suppression of serum non-esterified fatty acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1992

Octreotide inhibits the meal-induced increases in the portal venous pressure of cirrhotic patients with portal hypertension: a double-blind, placebo-controlled study.

The aim of this study was to determine the effects of the long-acting somatostatin analog, octreotide, on portal venous pressure and collateral blood flow in cirrhotic patients with portal hypertension during fasting and postprandial states. In a double-blind, placebo-controlled study, we investigated the effects of octreotide on the hepatic venous pressures and azygos blood flow of 21 patients before and after a standard liquid meal containing 40 gm of protein in 250 ml. Octreotide significantly reduced azygos blood flow from a mean of 499 +/- 65 ml/min to a mean of 355 +/- 47 ml/min (p < 0.01), but it had no effect on the hepatic venous pressure gradient. The hepatic venous pressure gradient of patients in the placebo group increased significantly, from a fasting mean of 16.4 +/- 1.6 mm Hg to a mean of 20.0 +/- 1.7 mm Hg 30 min after the meal (p < 0.01). In a second protocol hepatic venous pressures were measured in 20 patients at 30-min intervals for 2 hr after ingestion of the mixed meal. Again the placebo group showed a significant increase in the hepatic venous pressure gradient 30 min after the meal (20.4 +/- 1.5 mm Hg vs. 18.2 +/- 1.2 mm Hg; p < 0.05), but the group receiving octreotide showed no significant changes during the 2 hr of observation. We conclude that octreotide significantly reduces azygos blood flow, with little effect on portal venous pressure, and that it appears to inhibit postprandial increases in portal pressure in cirrhotic patients with portal hypertension.

Blood Flow Velocity↗
PubMed1992

Increased Na(+)-dependent D-glucose transport and altered lipid composition in renal cortical brush-border membrane vesicles from bile duct-ligated rats.

Erythrocyte membranes of patients with liver disease are characteristically enriched in cholesterol, a change known to impair several carrier-mediated membrane transport functions. In the present study we have assessed whether experimental liver disease can affect the membrane lipid composition and transport function of kidney epithelial cells. Small (about 5%) but significant (P less than 0.01) increases were found in the cholesterol-to-phospholipid molar ratio (C/PL) of rat renal cortical brush-border membrane (BBM) vesicles 3, 8, and 15 days after bile duct ligation which correlated closely with increased fluorescence polarization, i.e., decreased membrane fluidity (r = 0.75, P less than 0.001; n = 27). A lipoprotein-mediated pathogenesis was suggested by the close relationship between BBM C/PL and plasma C/PL (r = 0.69, P less than 0.001). The mean high-affinity Na(+)-coupled D-glucose uptake by BBM vesicles was higher 1, 3, 8, and 15 days after ligation than in non-operated rats, significantly so at 3 and 8 days (611 +/- 37 and 593 +/- 22 vs. 507 +/- 21 pmol/mg protein per 4 sec; P less than 0.05), and was positively correlated with BBM C/PL (r = 0.58, P less than 0.01) and fluorescence polarization (r = 0.41, P less than 0.05). Brief incubation of BBM vesicles from normal rats with cholesterol-rich phospholipid liposomes simultaneously increased BBM C/PL and Na(+)-dependent D-glucose uptake. Stimulation of BBM Na(+)-glucose cotransport in ligated rats was not due to delayed dissipation of the Na+ gradient or to a more rapid development of membrane potential. High-affinity Na(+)-dependent D-glucose uptake kinetics in 3-day bile duct-ligated rats showed a lower Kt, without an alteration in maximum velocity, Vmax, compared to sham-operated animals (0.298 +/- 0.015 vs. 0.382 +/- 0.029 mM; P less than 0.05), whilst the binding dissociation constant, Kd of high-affinity phlorizin binding sites was reduced by ligation (0.453 +/- 0.013 vs. 0.560 +/- 0.015 microM; P less than 0.001). We conclude that an early effect of bile duct ligation is to enrich renal cortical brush-border membranes in cholesterol, thereby decreasing membrane fluidity and stimulating Na(+)-dependent D-glucose uptake by increasing the affinity of the carrier.

Animals↗