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Biomedical subjects

N Tygstrup

Publications and source records attributed to N Tygstrup.

At least 91 records · Page 5Linked to original sources
PubMed1983

Insulin sensitivity in alcoholic cirrhosis.

The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the 'glucose clamp technique'. Fasting glucose and insulin were 5.4 +/- 0.3 mmol/l and 187 +/- 50 pmol/l (mean +/- SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/l) the glucose metabolic rate (divided by body mass) was 27 +/- 4 mumol X min-1 X kg-1 at an insulin concentration of 998 +/- 158 pmol/l. Thus the insulin sensitivity of the tissue glucose metabolism was 22 +/- 7 m3 X min-1 X kg-1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574 +/- 72 pmol/l. The resulting glucose metabolic rate was 20 +/- 4 mumol X min-1 X kg-1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783 +/- 172 pmol X min-1 X m-2. Fasting glucagon was 32 +/- 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.

Aged↗
PubMed1982

A simple method for determination of antipyrine clearance.

Antipyrine clearance (Cl(AP)) is widely used for assessment of microsomal liver function. The usual procedure involves collection of 4 to 7 samples of plasma or saliva obtained during 24 to 48 hr. To determine whether this procedure could be simplified it was compared with one based on a single sample (sCl(AP)) and an estimated volume of distribution (V(D)) in 142 persons. VD was estimated from body weight, in kilograms (BW), height, in centimeters (BH), age in years, and sex, or assumed to be 40 l. The agreement between values of Cl(AP and sCl(AP) increased with the time of the single sample and the two clearance estimates were nearly identical in all cases when the sample was taken after 18 hr. The method used for assessment of V(D) had only a small influence on the agreement. It is suggested that antipyrine clearance (in ml/min) is estimated as (formula: see text) where D is the dose of antipyrine (in mg), c(t) the concentration of antipyrine (in mg/t) at sampling time t (in min), t should be about 1440 min (24hr), and V(D) (in l) is calculated as 0.2363 X BW + 0.1962 X BH - 0.0272 X age - 10.26 (women) or 0.3625 X BW + 0.2239 X BH - 0.1387 X age - 14.47 (men). Little information is lost, however, if a fixed volume of 40 l is used. Then, if the dose is l gm, c(t) is expressed in milligrams per liter, and the sampling time is 24 hr, sCl(AP) = (3.28 - ln c(t)) X 28 ml/min.

Adult↗
PubMed1982

Prednisone treatment of chronic liver disease. I. Chronic aggressive hepatitis as a therapeutic marker.

A liver biopsy material comprising 477 biopsies from 477 patients included in a prospective, unblinded, randomized trial of treatment of cirrhosis with prednisone has been re-evaluated using new and more restrictive histological criteria for the diagnosis of cirrhosis and chronic aggressive hepatitis (CAH). The material was divided according to the likelihood of cirrhosis being present: (A) cirrhosis (287 patients), (B) probably cirrhosis (101 patients) and (C) compatible with but not diagnostic for cirrhosis (89 patients). Each group was further divided according to the presence (I) or absence (II) of CAH. A total of 98 patients fulfilled the histological criteria for CAH. The effect of prednisone concerning survival was evaluated in each group. In the total group of patients with CAH a significant beneficial effect of prednisone was found (p = 0.04). Among these patients the subgroup with cirrhosis in addition (group I A) also showed a significant effect of prednisone, while groups I B and I C only had a trend towards a beneficial effect (p = 0.44 and p = 0.36, respectively). In patients without CAH in the biopsy (Group II, A + B + C), no effect of prednisone was seen although a trend towards a harmful effect was found in patients with cirrhosis (Group II A). Control patients with CAH in all three subgroups had an insignificantly shorter survival than patients without CAH. All the CAH groups significantly more often included female patients with no history of alcoholism and a lower frequency of spider naevi. In addition, the CAH groups were more active as judged by biochemical and histological variables. It was further disclosed that the presence of large piecemeal necroses indicated a favourable effect of prednisone treatment, while alcoholism, ascites and male sex acted as indicators for an unfavourable treatment effect.

Biopsy↗
PubMed1982

Prednisone and chronic liver disease. II. Clinical versus morphological criteria for selection of patients for prednisone treatment.

A prospective, unblinded, randomized trial of treatment of cirrhosis and chronic aggressive hepatitis (CAH) with prednisone included 484 patients who were divided using both the clinical criteria: non-alcoholic females without ascites, and the morphological criterion: presence of a liver biopsy showing CAH. A total of 164 patients (34%) satisfied the three clinical criteria and biopsies from 95 patients (20%) showed CAH. By a cross-tabulation method between the two sets of criteria, four groups were formed. Evaluation of the treatment effect by means of relative death rate showed that the clinical criteria identified both a group of patients with a beneficial effect of prednisone (p less than 0.05) and a group with a harmful effect of the treatment (p less than 0.05). Patients with CAH also had a significant beneficial treatment effect, but patients without CAH showed only an insignificantly harmful effect of treatment. Patients fulfilling both sets of criteria had a beneficial effect of prednisone (p less than 0.05) and patients lacking both sets had a significantly harmful treatment effect. A significantly better survival was found in patients satisfying the clinical criteria without CAH in the biopsy than in patients with CAH and not fulfilling the clinical criteria (p = 0.03). In both the groups of patients with disagreement between the two sets of criteria, a trend towards a beneficial effect of prednisone was found. It is concluded that the simple clinical criteria in comparison with the histological criteria identify a larger group of patients with a beneficial effect of treatment.

Chronic Disease↗
PubMed1981

Clinical relevance of restrictive morphological criteria for the diagnosis of cirrhosis in liver biopsies.

Material obtained by needle biopsy of the liver from 532 patients with cirrhosis who had previously been examined has been re-evaluated using new and more restrictive histological criteria for the diagnosis of cirrhosis. The material was divided into four main groups: (A) cirrhosis, 287 biopsies; (B) probably cirrhosis, 101 biopsies; (C) compatible with but not diagnostic for cirrhosis, 89 biopsies; and (D) probably not cirrhosis, 11 biopsies. Group E consisted of 44 cases where no or insufficient material was available. The survival curves of the groups were significantly (P less than 0.05) different, with group D having the best survival followed by C, B and A. Clinical and laboratory manifestations of cirrhosis (more than five spider naevi, presence of ascites, daily alcohol intake of more than 50 g) were found significantly (P less than 0.05) more often among patients from group A, followed by patients from groups B, C and D. It is concluded that the more restrictive histological criteria for the diagnosis of cirrhosis in liver biopsies have clinical relevance, due to the prognostic and therapeutic implications of the diagnosis. The study also underlines the importance of specifying the criteria used when studies of patients with cirrhosis are reported.

Biopsy↗
PubMed1981

Continuous reaction time in patients with hepatic encephalopathy. A quantitative measure of changes in consciousness.

In 14 patients with encephalopathy due to cirrhosis of the liver levels of consciousness were assessed by clinical ratings and continuous reaction time measurements. The observations were compared with similar measurements made in patients with chronic brain syndrome, patients sedated with diazepam, and hospitalized controls. Patients with hepatic encephalopathy were characterized by having slower reaction times than patients from the other groups. Furthermore, the performance of several liver patients was decreasing during the test. This phenomenon was not seen in the other groups. The continuous reaction times in the liver patients were correlated with the clinical ratings, but the reaction times appeared to be more sensitive, since on several occasions this test became abnormal before the clinical rating. Patients dying within 3 months after the test had more abnormal reaction times than patients surviving this period, indicating a relation between this test and the severity of the liver disease.

Adolescent↗
PubMed1981

Aspects of the natural history of gastrointestinal bleeding in cirrhosis and the effect of prednisone.

The natural history of gastrointestinal bleeding in cirrhosis has been studied using prospectively collected data of 532 patients included in a randomized clinical trial with a regular follow-up of up to 12 yr. Of the total 199 patients who experienced gastrointestinal bleeding, 95 (48%) bled from esophageal or gastric varices, 67 (34%) bled from peptic ulcer or gastritis, and 37 (18%) had either insufficient evidence of the source (33) or mixed sources (4). In the total group of patients the cumulative percentage of patients in whom varices had been demonstrated of patients in whom varices had been demonstrated by radiography increased from 12 to 90 in 10 yr, while that of bleeding from varices increased from 7 to 40. In 104 patients who bled for the first time during the trial period (trial bleeding patients) the median number of bleeding episodes was one (range 1-8). In these patients the fatality from bleeding from varices was 82%. The risk of rebleeding from varices was 81%, and 4 yr after the first bleeding the cumulative survival had decreased to less than 10%. Rebleeding was significantly less frequent and survival significantly higher in patients bleeding from sources other than varices. Prednisone reduced the occurrence rate of varices, bleeding from varices, and death from bleeding varices in nonalcoholic females without ascites, 40% of whom fulfilled the histologic criteria of chronic active hepatitis. Prednisone significantly increased the occurrence rate of varices inpatient with ascites and of bleeding from varices in alcoholic patients. Prednisone significantly increased the occurrence rate of peptic ulcer in males and in patients without chronic active hepatitis.

Clinical Trials as Topic↗
PubMed1980

Azathioprine in primary biliary cirrhosis: a preliminary report of an international trial.

The effects of azathioprine on the course of primary biliary cirrhosis were studied prospectively in a multinational, double-blind randomized clinical trial involving 236 patients, of which 124 received azathioprine and 112 placebo. No significant effects were seen on survival, clinical course, hepatic histologic features, hepatic tests, or immunologic abnormalities after a median follow-up period of 18 mo, but most of the trends observed were in favor of azathioprine. The results obtained so far indicate that the effect of azathioprine as a single treatment is limited and probably of little clinical importance, but more years of follow-up will be needed to provide a definite conclusion.

Actuarial Analysis↗
PubMed1980

Clinical pattern and course of disease in primary biliary cirrhosis based on an analysis of 236 patients.

A prospective study of the clinical pattern and course of primary biliary cirrhosis based on the data of 236 patients (211 females, 25 males) in an international randomized trial has been performed mainly using life-table technique. The median follow-up period has been 18 mo. After the entry into the study, at which time the median duration of symptoms was 2.1 yr, the estimated 5-yr increase in the cumulative percentage of patients was for pruritus from 75% to 95%, jaundice 59% to 82%, hepatomegaly 54% to 86%, pigmentation 54% to 85%, xanthomas 27% to 50%, GI bleeding 17% to 46%, ascites 7% to 49%, and vertebral collapse 3% to 20%. The frequency of cirrhosis increased from 30% to 82% in 4 yr. The mitochondrial antibody titer showed a high rate of progression with time. In analysis of subgroups, age, histologic stage, and particularly the serum bilirubin level were important prognostic factors. Sex, duration of symptoms, and character of first symptom or sign had no independent prognostic influence. The most important indication of seriously progressive course was rapid development of severe cholestasis independent of the histologic stage.

Adult↗
PubMed1979

The physiologic basis for clearance measurements in hepatology.

Three hepatic clearance regimes (flow-limited, general, and enzyme-limited) can be defined from a model of hepatic perfusion-elimination relationships. Substances that can be used for clearance measurements can thus be classified into three categories according to the relation between their kinetic elimination constants (Vmax, Km) and hepatic blood flow. The pathophysiologic and clinical importance of the clearance regimes is discussed with special emphasis on the effect of changes in hepatic blood flow and liver function. The criteria for choosing test substances within each regime are stated. This choice depends on the object of study for a clearance measurement (blood flow, drug elimination, liver function). Only the enzyme-limited clearance regime is suited for direct assessment of quantitative liver function ('true clearance'), while the other regimes depend more or less on blood flow.

Animals↗