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Biomedical subjects

N Tygstrup

Publications and source records attributed to N Tygstrup.

At least 19 recordsLinked to original sources
PubMed1992

Who benefits from endoscopic sclerotherapy of bleeding oesophageal varices? Proposal for differential indications. The Copenhagen Esophageal Varices Sclerotherapy Project.

The value of early sclerotherapy for variceal haemorrhage remains unsettled, possibly because the treatment may be beneficial to some patients and harmful to others. On the basis of a randomized clinical trial of sclerotherapy in 187 patients presenting with their first variceal haemorrhage, we examined the relationship between clinical, endoscopic and biochemical characteristics at admission and the treatment effect on mortality. As previously published, sclerotherapy had no overall effect on the very high mortality during the first 6 weeks (47%), but thereafter the mortality and risk of rebleeding were reduced. The analysis showed that in the 48% of the patients with disturbed consciousness and/or elevated plasma creatinine, sclerotherapy considerably increased short-term mortality, and this was not compensated for by increased long-term survival. Among patients without these characteristics, sclerotherapy reduced mortality in the 25% with ascites, but did not affect short-term mortality in the 27% without. Sclerotherapy significantly improved the long-term survival of these patients. The results suggest that sclerotherapy should not be used in patients with disturbed cerebral or renal function, whereas it may be beneficial in patients without these characteristics.

Adult↗
PubMed1992

High volume plasma exchange in fulminant hepatic failure.

We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure > 110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Acetaminophen↗
PubMed1990

Effect of dietary protein on the capacity of urea synthesis in rats.

The in vivo capacity of urea nitrogen synthesis (CUNS) during alanine stimulation was measured within the blood amino acid concentration interval 7.3-11.6 mmol/l, where urea synthesis is at maximum and independent of substrate concentration. Three groups of rats were fed for 14 days, either a low protein diet (8%), a normal diet (17%), or a high protein diet (53%). Diet protein modified both CUNS and plasma glucagon concentration. CUNS was 5.86 +/- 2.93, 7.43 +/- 2.16, and 19.31 +/- 4.32 mumol/(min.100 g BW) (mean +/- SD, N = 6), respectively. The corresponding plasma glucagon concentrations after alanine stimulation were 222 +/- 400, 633 +/- 229, and 1700 +/- 627 ng/l, respectively. The in vivo kinetics of urea production is regulated by dietary protein, possibly via glucagon. This implies that the liver plays an active part in adaptation of whole body nitrogen homeostasis to dietary changes.

Alanine↗
PubMed1990

Galactose removal kinetics during hypoxia in perfused pig liver: reduction of Vmax, but not of intrinsic clearance Vmax/Km.

The galactose elimination kinetics was examined in five perfused pig livers of 1.2 kg during hypoxia induced by administration of 2, 4 or 7% oxygen in the oxygenator instead of 20% as used in nine control experiments, previously published. Galactose was given as four to five successive constant infusion rates so that successive steady-state period with galactose concentrations from 0.04 to 5 mmol l-1 were obtained in each experiment. From the relationship between the calculated elimination rate and the perfusate galactose concentration, values of the maximal elimination rate Vmax and the half saturation concentration Km were calculated. Both Vmax and Km were reduced by hypoxia: the lower the oxygen supply, the greater the reduction. Vmax was about 0.08 mmol min-1 kg-1 liver at 2% oxygen and about 0.18 mmol min-1 kg-1 liver at 4-7% oxygen; both being significantly lower than the value of 0.43 mmol min-1 kg-1 liver at 20% oxygen. Km was about 0.07 mmol l-1 at 2% oxygen and 0.13 mmol l-1 at 7% oxygen; both significantly lower than the value of 0.23 mmol l-1 at 20% oxygen. A nearly parallel reduction of liver ATP concentration and galactose Vmax indicates that the galactose Vmax may reflect the phosphorylation capacity of the liver cells. The Vmax/Km ratio (intrinsic hepatic clearance) was unchanged during hypoxia.

Animals↗
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↗
PubMed1978

Clinical aspects of drug-induced hepatitis.

The drug reactions of the liver may be classified as to (1) reproducibility, (2) severity, (3) localization and (4) duration of the lesion. Ad 1) Few drugs give a reproducible, dose dependent, hepatic reaction (e.g. acetaminophen), a greater problem is the unpredictable, dose independent reactions caused by "indirect" hepatotoxic drugs (e.g. imipramin). Ad 2) Drug reactions may be fatal (e.g. halothane), of limited clinical importance (e.g. clorpromazin) or clinically insignificant (e.g. iopanoic acid). Ad 3) Histologically, and to some extent clinically, hepatocellular (e.g. propylthiouracil) may be distinguished from cholestatic (e.g. tolbutamide) reactions, but overlapping (e.g. phenylbutazone) and individual variations are common. Ad 4) Most drug reactions are acute, but an insiduous course, developping to cirrhosis, is increasingly recognized (e.g. oxyphenacetin). Drug reactions are usually not clinically, biochemically and morphologically distinct from other common liver diseases and are only diagnosed if this possibility is constantly kept in mind. Treatment other than withdrawal of suspected or known etiologic agents is virtually lacking. The basis for prophylaxis is careful registration of all drug reactions. Potentially hepatotoxic drugs should only be administered after thorough cost/benefit considerations.

Chemical and Drug Induced Liver Injury↗
PubMed1978

Treatment of gastric ulcer. The randomized clinical trials from 1964 to 1974 and their impact.

Twenty-nine randomized clinical trials (RCTs) from the decade 1964-74 evaluating treatments of gastric ulcer have been analyzed. None of them ful-filled all criteria for an ideal RCT. The most frequent shortcomings were: short treatment or follow-up periods, incomplete description of the patients included, small patient samples, suboptimal experimental design, lack of double-blind testing, high number of drop-outs, less precise or less relevant types of evaluation of the treatment effect, uncontrolled ancillary treatment, or lack of statistical evaluation of the results. The most frequently tested drug was carbenoxolone, which has been shown to be clearly effective. Judged by the effect on the recommendations in standard medical textbooks the impact of the best RCTs have been small. This situation emphasizes the need for more well-planned and performed RCTs on treatments of gastric ulcer.

Adult↗
PubMed1977

Treatment of acute viral hepatitis with (+)-cyanidanol-3.

A double-blind trial of (+)-cyanidanol-3 (2 g/day) versus placebo tablets was carried out in 100 patients with acute viral hepatitis. 51 received the drug and 49 placebo. (+)-Cyanidanol-3 accelerated the disappearance of HBsAg from the blood, lowered serum-bilirubin, and relieved symptoms such as anorexia, nausea, and pruritus. The drug was well tolerated. None of the patients had a relapse of acute hepatitis. Chronic active hepatitis developed in 1 of the placebo-treated patients. Thus, (+)-cyanidanol-3 seems to be of benefit in acute viral hepatitis.

Adult↗
PubMed1977

The epidemiology of the gastrointestinal randomized clinical trial.

Has the randomized clinical trial (RCT), generally accepted as the method of choice for evaluation of most treatments, obtained a footing in gastroenterology? Among 35,228 citations on gastroenterologic therapy indexed in MEDLARS 1964-1974 306 (0.9 per cent) were RCT's. During the decade their frequency rose significantly (P less than 0.05) from 0.3 per cent in 1964 to 1.7 per cent in 1973. The "typical" RCT was a double-blind two-group comparison of a new and an established drug on the symptoms of peptic ulcer; 50 patients were followed for six weeks, and the number of dropouts was unknown. The new drug was found to be more effective. It is postulated that the RCT's in gastroenterology are quantitatively and qualitatively insufficient and that co-ordinated planning of RCT's and uninhibited publication of statistically proved negative results may help to ensure that the patient with gastrointestinal disease receives the best available treatment.

Europe↗
PubMed1977

Effect of sites of blood sampling in determination of the galactose elimination capacity.

The galactose elimination capacity was calculated from both arterial and capillary or peripheral venous curves in twenty patients. The capillary curves on the average were delayed 1.4 min in relation to the arterial curves. No significant difference was found between the calculated galactose elimination capacity from either curve. On the average the slope of the venous curves was smaller than that of the arterial curve, and their time delay was very variable (from 1.55 to 5.27 min). Galactose elimination capacity calculated from venous curves was smaller than those calculated from arterial curves, especially in patients with a high galactose elimination capacity. Capillary blood sampling may replace arterial puncture for routine use, whereas venous blood sampling introduces a significant bias.

Adult↗
PubMed1977

Significance of suspected "chronic aggressive hepatitis" in acute hepatitis.

Transition from acute to chronic hepatitis has important prognostic and therapeutic implications. In 17 patients with acute viral hepatitis, observed during a period of 7 years, a liver biopsy showed changes compatible with chronic aggressive hepatitis and superimposed acute hepatitis. Follow-up biopsies showed normal liver in 14 cases, chronic persistent hepatitis in 1, and cirrhosis in 2. In 12 cases the initial biopsy which showed changes suggestive of chronicity was taken 1 month after onset of symptoms of acute hepatitis, or later. Cases developing chronic liver disease showed no characteristic clinical, laboratory, or histological features at the time of the first biopsy. If the diagnosis of chronic active hepatitis is based on histological findings alone in patients with prolonged acute hepatitis, the incidence of this condition will be grossly overestimated. The transition from acute to chronic hepatitis cannot be recognized with any degree of certainty by presently available methods.

Acute Disease↗