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Biomedical subjects

L Ranek

Publications and source records attributed to L Ranek.

At least 19 recordsLinked to original sources

DNA polymorphism of HLA class II genes in primary biliary cirrhosis.

We investigated the DNA restriction fragment length polymorphism of the major histocompatibility complex class II genes: HLA-DRB, -DQA, -DQB, DPA, -DPB, the serologically defined HLA-A, B, C, DR antigens, and the primed lymphocyte typing defined HLA-DP antigens in 23 Danish patients with primary biliary cirrhosis (PBC) and in healthy Danes. The following genetic markers were found with increased frequencies in PBC: HLA-B8 (relative risk, RR = 2.4, P less than 0.05, 'corrected' P greater than 0.05), HLA-DR3 (RR = 3.4, P less than 0.01, 'corrected' P less than 0.05), the DRB3*01/02/03 (DRw52) associated DRB Bgl II 9.1 kilobase (kb) fragment (RR = 2.9; P less than 0.05, 'corrected' P greater than 0.05), the DQA1*0501 associated DQA Taq I 4.8 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05), the DQB1*0201 (DQw2) associated DQB Hin dIII 11.5 kb fragment (RR = 3.1; P less than 0.05, 'corrected' P greater than 0.05). No DNA fragments specific for DRB1*0301 (DR3) could be identified. The frequencies in PBC of other genetic markers including DRw8, DRB1*08, HLA-DP antigens, DPA, and DPB genes did not differ significantly from those in controls. The associations between PBC and B8, DR3, DQA1*0501, and DQB1*0201, which are frequently found together on the same haplotype, are at variance with recent reports on associations between PBC and Drw8. The discrepancy suggests that PBC is genetically heterogenous.

Genes, MHC Class II

Glutathione treatment of hepatocellular carcinoma.

This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth status of the tumor (progression, stagnation or regression). All the patients, except a male with a fibrolamellar type of HCC, died within 1 year after diagnosis. Two women with moderately advanced tumors survived almost 1 year, tumor growth stopped or regressed and in one of the women an initially abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue this hypothesis.

Adult

The influence of disulfiram on acetaminophen metabolism in man.

1. Acetaminophen clearance and its partial clearance to its major metabolites has been determined before and after 5 days treatment with the anti-alcohol abuse agent disulfiram (200 mg daily). The study was conducted in 10 subjects, five without liver disease and five with alcoholic cirrhosis of the liver. Acetaminophen was given i.v. at a dose of 500 mg. Plasma samples were obtained up to 8 h after injection and urine collected for 24 h. 2. Across all subjects acetaminophen plasma clearance was reduced from 0.249 +/- 0.061 to 0.217 +/- 0.066 l/min after disulfiram treatment (mean +/- SD, P less than 0.05). Thus no change in acetaminophen dosage would be required in patients treated with disulfiram. 3. The partial clearance of acetaminophen to its glucuronide, sulphate and glutathione derivatives (i.e. cysteine and N-acetyl cysteine) was not significantly changed by disulfiram treatment. Thus it seems unlikely that the previously observed protective effects of disulfiram against acetaminophen-induced hepatotoxicity in animals due to inhibition of metabolism will be seen in man.

Acetaminophen

Halothane hepatitis.

Halothane (2-bromo-2-chloro-1:1:1-trifluoroethane) is a volatile, nonflammable anaesthetic agent which has been widely used for the last 20 years. Halothane hepatitis has been a matter of continuing controversy, but now it seems to be generally accepted as a clinical entity. Characteristically the halothane hepatitis occurs after multiple exposures to halothane within short time. The pathogenesis of the liver cell damage is obscure. It is estimated that the incidence of halothane hepatitis is about one per 8000 halothane anaesthesias and the lethality about one per 40000. Prophylaxis consists of avoiding repeated halothane anaesthesias within short time and to avoid re-exposure to halothane if otherwise unexplained liver damage has occurred after halothane.

Chemical and Drug Induced Liver Injury

Encephalopathy in patients with cirrhosis of the liver. A neuropsychological study.

Neuropsychological tests and clinical ratings of the level of consciousness were performed in 30 patients with encephalopathy due to cirrhosis of the liver. Compared to the test norms for patients with diffuse cerebral lesions, the state of encephalopathy in patients with cirrhosis has a qualitatively different pattern of cerebral affection, since disturbances of attention were found independently of general intellectual function. Eight cirrhotic patients without portacaval anastomosis were matched in clinical rating with 8 patients with portacaval anastomosis. The course of cerebral affection after portacaval shunts showed defects characteristic of intellectual impairments in diffuse cerebral lesions, which were not found in the non-operated matched controls.

Adult

Splanchnic blood flow in patients with abdominal angina before and after arterial reconstruction. A proposal for a diagnostic test.

The diagnostic value of determining the splanchnic blood flow (SBF) and oxygen uptake before and after a test meal in patients suspected of abdominal angina was investigated in 15 patients with unexplained abdominal pain. Six patients with typical abdominal angina and occlusive lesions of two or three splanchnic arteries were investigated before and after successful arterial reconstruction. Five patients with less severe arterial lesions were classified as suspected of abdominal angina and four patients with eventual normal arteriography served as controls. No significant difference was found in fasting SBF between the three groups. Postprandial SBF rose in the controls and in the abdominal angina suspected group, but not in the patients with abdominal angina. After arterial reconstruction fasting SBF was higher than before and postprandial SBF rose to the level of the controls. No difference in oxygen uptake before or after test meal was seen in any of the groups or after arterial reconstruction.

Abdomen

Increased transcapillary escape rate of albumin in patients with cirrhosis of the liver.

The transcapillary escape rate of albumin (TERalb), i.e. the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected 125I-labelled human serum albumin during the first 60 min after injection in nine patients with cirrhosis of the liver. Six of the patients had ascites. The wedged hepatic venous pressure or splenic pulp pressure ranged from 20 to 30 mmHg, mean 26 mmHg. Plasma albumin concentration was low, but plasma volume was slightly enlarged, and thus the intravascular mass of albumin was only moderately reduced. The transcapillary escape rate of albumin was significantly elevated in all the cirrhotics, mean 10.2%/h, range 8.8 to 12.3%/h, in comparison to values for twenty-eight normal subjects 5.4%/h, range 3.5-7.2%/h. Our results can best be explained by increased filtration out of the vessels in the portal system, due to the increased portal venous pressure. The increased TERalb probably contributes to the formation of oedema and ascitic fluid.

Adult

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

Cytophotometric studies of the DNA, nucleic acid and protein content of liver cell nuclei from patients with virus hepatitis.

Cytophotometric studies of the DNA, nucleic acid and protein content of liver cell nuclei from patients with virus hepatitis. Acta path. microbiol. scand. Sect. A, 84: 1-8, 1976. With a view to investigating some of the causes why the size of liver cell nuclei increase in virus hepatitis, the nuclear size and the nuclear contents of DNA, nucleic acid and protein were measured by cytophotometry. The liver cell nuclei could be grouped in classes according to their contents of DNA, nucleic acid, and protein and, as in control livers, diploid nuclei were always most frequent. Nuclei with intermediate DNA values, probably S-phase nuclei, were more frequent in hepatitis livers than in controls. The average size of nuclei from patients with hepatitis was significantly larger than that from controls, whereas the DNA content was the same. A significant, positive correlation between nucleic acid content, protein content and nuclear area was found. The high correlation between nuclear protein content and nuclear size simultaneously with the increased nuclear size during hepatitis is assumed to reflect an increased nuclear function.

Acute Disease

Galactose elimination capacity as a prognostic index in patients with fulminant liver failure.

In 25 patients with fulminant hepatic failure the prognostic value of a quantitative liver function test, the galactose elimination capacity, was assessed and comapred with routine liver function tests and clinical features. The galactose elimination capacity was significantly higher (P less than 0-05) in the five patients who survived than in the 20 patients who died. None of the other liver function tests, was significantly different. The values of the galactose elimination capacity overlapped considerably between survivors and non-survivors, but all patients with a galactose elimination capacity below 12-8 mumol galactose/min and kg body weight died. The disease among most patients who died having a galactose elimination capacity greater than 13 mumol ran a subacute course. It is suggested that quantitative liver function tests be included when new treatments of fulminant hepatic failure are investigated.

Adolescent

Liver impairment during chronic hemodialysis and after renal transplantation.

Liver impairment has been evaluated in a consecutive series of 79 patients with chronic renal failure of whom 23 were treated with hemodialysis alone and 37 with hemodialysis and renal transplantation alone. In half of the chronic hemodialysis patients and half of the patients receiving a renal allograft elevation of serum alanine aminotransferases was observed for a shorter or longer period during the study. In half of these cases from both groups the clinical course, laboratory data and liver histology were consistent with virus hepatitis and four patients died from fulminant hepatic failure. In the other half of the patients with elevated transaminases, this was either asymptomatic and unexplained or due to other causes such as septicaemia or urinary leakage. Liver biopsy showed unspecific changes. Renal transplantation was not performed in patients suffering from virus hepatitis, but 12 of the 37 patients who received a renal allograft had elevated aminotransferases at the time of transplantation. In seven of them a marked increase in aminotransferase was observed postoperatively, but none developed clinical sign of liver disease. It is concluded that elevated aminotransferase activity per se is no contraindication to surgical procedures, including renal transplatation, in these patients. However, a liver biopsy should be performed to detect a possible liver disease.

Alanine Transaminase

A morphometric study of normal human liver cell nuclei.

Using the projecting method, measurements were made of the size of nuclei of liver cells in liver biopsies taken from ten patients with normal liver histology and normal liver function tests and from two patients with acromegaly. For the statistical analysis a parametric model of the distributions of the nuclear radii, the chi distributions, was used, making an estimation of the frequencies of di-, tetra- and octaploid nuclei possible. The distribution of the lengths of the nuclear radii was consistent with normal distributions corresponding to the different ploidy classes. Diploid nuclei constituted 84 to 99 per cent of the liver cell nuclei, and the frequency of polyploid nuclei increased with increasing age. Samples of nuclei within the same biopsy revealed significant differences in the mean radius of diploid nuclei and in the frequency of polyploid nuclei. This biological variation must be taken into account in the interpretation of karyometric data. One of the patients with acromegaly had a higher frequency of polyploid nuclei than seen in normal patients, and in both patients with acromegaly the size of diploid nuclei was large compared with normals. The frequency of binuclear nuclei was unrelated to age and frequency of polyploid nuclei, but males were found to have more binuclear liver cells than females.

Acromegaly

Karyometry of liver biopsies in virus hepatitis.

Liver biopsies from ten patients with clinically mild or moderate acute virus hepatitis, taken in the acute phase of the disease and in the recovery phase or later, were assessed for the size of liver cell nuclei and the number of binuclear nuclei. A parametric model of the distributions of the nuclear radii was used to estimate the mean nuclear radius of diploid nuclei and the frequencies of di-, tetra- and octaploid nuclei. During the acute phase of virus hepatitis the liver cell nuclei were often larger, with greater variation in size, than in the recovery phase. This pleomorphism was not only due to pyknotic and necrotic nuclei as these were not measured. It is assumed that the enlargment of the nuclei was due to increased metabolic activity of the nuclei. The frequencies of polyploid nuclei and binuclear liver cells were higher in the first biopsies, probably reflecting regenerative activity. No correlation was found between the severity of the disease as judged by liver histology or routine liver tests and the degree of nuclear changes with respect to size and frequency of polyploid or binuclear liver cells.

Acute Disease

Liver failure and drug metabolism.

The hepatic microsomal metabolism of antipyrine, as measured by its metabolic clearance, was investigated in 18 patients either before, during, or after hepatic encephalopathy. The antipyrine clearance measured in 13 patients during hepatic encephalopathy (4.6 ml/min. S.D. 14) was significantly lower than that of 5 patients investigated 4 weeks before or after hepatic encephalopathy (9.6 ml/min. S.D. 1.9). The clearance of antipyrine as a measure of a quantitative liver function is substantiated by the present observations, and its use as a prognostic indicator of acute liver failure is suggested.

Adolescent

The nuclear dry weight of liver cells from patients with virus hepatitis and from controls.

Interferometric investigations were performed at liver cell nuclei isolated in 70 per cent glycerol. In 11 patients with virus hepatitis and seven patients without liver disease the nuclear dry weight of liver cells obtained by liver biopsy was determined by interferometry. The average nuclear dry weight of diploid liver cells from controls was 39.9 pg while an average value of 45.4 pg was found for patients with hepatitis. The corresponding nuclear volumes were 241 and 274mu3 respectively. The dry mass and volume of tetraploid nuclei was twice as big as that of diploid nuclei in both materials. The nuclear water content was neither significantly different between diploid and tetraploid nuclei nor significantly different between nuclei from controls and patients with hepatitis.

Cell Nucleus