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Biomedical subjects

L Ranek

Publications and source records attributed to L Ranek.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1989

Vitamin D, parathyroid hormone, and bone mineral content of lumbar spine and femur in primary biliary cirrhosis.

In order to elucidate the pathogenesis and degree of osteopoenia in primary biliary cirrhosis (PBC) we conducted a cross-sectional study of 47 non-selected female patients with biopsy-proven PBC. Bone mineral content (BMC) of the lumbar spine, femoral neck and femoral shaft was determined using dual photon absorptiometry. Compared to healthy females of corresponding decades the PBC patients exhibited significantly decreased mean BMC-values in lumbar spine (88%, P less than 0.05) and femoral neck (92%, P less than 0.05) but not in femoral shaft (96%, NS). Bone mineral content was not significantly associated with duration of liver disease, impairment of liver function (serum concentrations of albumin, clotting factors II + VII + X, bilirubin, alkaline phosphatase galactose elimination capacity or histology), variables reflecting calcium homeostasis (serum concentrations of ionized calcium, parathyroid hormone, vitamin D binding protein, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3) or previous treatment with glucocorticosteroids. In view of our negative findings we suggest that future studies in this field should focus on physical activity and female sex hormones as determinants for the prevention of osteopoenia in females with primary biliary cirrhosis.

Adult↗
PubMed1989

NcoI restriction fragment length polymorphism (RFLP) of the tumour necrosis factor (TNF alpha) region in primary biliary cirrhosis and in healthy Danes.

The restriction fragment length polymorphism of the human tumour necrosis factor (TNF alpha) region was investigated by means of 20 different restriction enzymes and a human TNF alpha cDNA probe. Only one of the enzymes, NcoI, revealed a polymorphic pattern consisting of fragments of 10.5 and 5.5 kb, which behaved as alleles. In a panel of 108 random, healthy, unrelated Danes, the phenotype frequencies of the 10.5 and 5.5 kb bands were 0.94 and 0.53 and the gene frequencies were 0.71 and 0.29, respectively. The test for Hardy-Weinberg equilibrium showed no significant deviation from the expected values. The 5.5 kb band was strongly positively associated with HLA-DR3, HLA-B8, and HLA-A1. In 22 patients with primary biliary cirrhosis a significantly (corrected P = 0.024) decreased frequency of the 10.5 kb fragment was found. Additional studies are in progress to substantiate this association.

Chromosome Mapping↗
PubMed1989

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases.

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range in healthy young subjects (age, 23-42 years) was 44-61 ml/100 g/min; in patients with grade I + II encephalopathy (mean +/- SEM) it was 32.8 +/- 3.6 ml/100 g/min in acute (n = 4; age, 28 +/- 8 years) and 37.0 +/- 3.3 ml/100 g/min in chronic liver patients (n = 10; age, 51 +/- 2 years). In grade III + IV encephalopathy it was 28.7 +/- 3.8 ml/100 g/min in acute (n = 8; age, 28 +/- 3 years) and 32.9 +/- 3.7 ml/100 g/min in chronic patients (n = 12; age, 49 +/- 3 years). CBF did not correlate with the liver function and was of no prognostic value. The liver function was markedly reduced in all the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.

Adult↗
PubMed1988

Delta infection and hepatitis B virus replication in Danish patients with fulminant hepatitis B.

The presence of hepatitis B virus and delta agent markers was investigated in 41 patients referred during the years 1970-1985 with fulminant hepatitis classified as type B or non-A non-B and compared to findings in patients with uncomplicated hepatitis B and chronic hepatitis B infection. 13 patients had no markers of hepatitis B and delta infection and were classified as non-A non-B hepatitis. The remaining 28 patients were all HBsAg and IgM anti-HBc positive and 14 (50%) had evidence of delta infection. In contrast, only 13/71 patients (18%) with acute benign hepatitis B had evidence of delta coinfection (p less than 0.005). This corresponds to an odds ratio of 4.5 for development of fulminant hepatitis among patients with hepatitis B and delta coinfection. In 100 chronic HBsAg carriers 29% were positive for delta markers. 12 of the delta infected patients with fulminant hepatitis were positive for total antibody to the delta antigen, and 2 were delta antigen positive. Three were HBeAg positive/anti-HBe negative. None had hepatitis B virus DNA. Among the 14 patients without delta infection, hepatitis B virus DNA was found in 2/4 HBeAg positive/anti-HBe negative patients and in 1/8 patients negative for both markers. The present data indicate that a high proportion of Danish patients with fulminant hepatitis B have hepatitis B and delta agent coinfection. Further, the findings suggest that hepatitis B and delta coinfection may be associated with an increased risk of development of fulminant hepatitis as compared to that of hepatitis B alone.

Adolescent↗
PubMed1978

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↗
PubMed1978

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↗
PubMed1977

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↗
PubMed1977

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↗
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↗
PubMed1976

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↗
PubMed1976

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↗