Inappropriately low levels of gonadotrophins in amenorrhoeic women with alcoholic and non-alcoholic cirrhosis.

We investigated a group of 111 amenorrhoeic females with associated liver disease. These comprised alcoholic cirrhotics (N = 38), non-alcoholic cirrhotics (N = 12), non-cirrhotic alcoholics (N = 21) and those suffering from other chronic liver diseases (N = 40) admitted to our medical department from 1986 to 1991. The serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), oestradiol, testosterone, sex hormone binding globulin (SHBG) and prolactin were measured. Serum LH was decreased below the normal range in 50% of patients with alcoholic cirrhosis and in 42% of patients with non-alcoholic cirrhosis. One third of non-cirrhotic alcoholics also had decreased LH, in contrast to only 8% of patients with other chronic liver diseases (p < 0.01). A close correlation was found between LH and FSH when all patients were pooled (r = 0.91, p < 0.001). A gonadotrophin-releasing hormone (GnRH) injection elicited a clear LH and FSH response in 11 out of 14 patients with cirrhosis, indicating that the hypothalamus rather than the pituitary is the site of disturbance in gonadotrophin secretion. Serum SHBG was within normal limits and similar in all four groups. In nine females with alcoholic cirrhosis who abstained for 3 months, serum SHBG increased significantly from 39 +/- 18 to 70 +/- 25 nmol/l (p < 0.001), while LH increased in five of nine females and was unchanged in four. In conclusion, half of the amenorrhoeic females with alcoholic as well as non-alcoholic cirrhosis had inappropriately low serum LH and FSH levels, indicating dysfunction of the hypothalamo-pituitary axis.(ABSTRACT TRUNCATED AT 250 WORDS)

The ultrastructure of the interfollicular epidermis of the hairless (hr/hr) mouse. V. The cytoplasm of the horny cells.

The ultrastructure of horny cells in the interfollicular epidermis of the hairless mouse and in the mouse with hair has been studied with particular emphasis on changes in the cytoplasm through the horny layer. Horny cells from the two strains have a similar appearance, and the horny layer can be divided into three sublayers, each with a different ultrastructure. It is suggested that in vivo the same arrangement of densely packed filaments and fibrils which represents the keratin pattern in the basal sublayer is preserved throughout the horny layer. However, the filaments and interfilamentous substance seem to undergo a continuous transformation, which possibly results in a disintegration of the filaments when desquamation of the uppermost cell takes place.

The ultrastructure of the interfollicular epidermis of the hairless (hr/hr) mouse. IV. Lamellated bodies (Odland bodies, membrane-coating granules) and intercellular material in the upper part of the granular and horny layers.

The appearance of the lamellated bodies (Odland bodies, membrane-coating granules, keratinosomes) and intercellular material in the upper part of the granular and horny layers of the interfollicular epidermis of the hairless mouse was studied. In order to obtain more information about these structures various fixation procedures were used. The bodies displayed a lamellated pattern after osmication and uneven staining of the lamellae was seen after osmium zinc iodide fixation. Glutaraldehyde fixation made the bodies appear electron-empty except for some electron-dense material mainly at their periphery. These observations indicate that the bodies are mainly composed of lipids. The bodies were discharged to the intercellular space in tthe upper part of the granular layer where they disintegrated. The appearance of the intercellular space in the horny layer varied considerably with the fixation procedure indicating that artefacts were produced during the processing of the specimens. Based on the observations after various fixation methods it is suggested that the intercellular space in vivo is completely filled with a substance which stained weakly osmiophilic. In this substance very osmiophilic structures of various shapes and sizes may be present.

[Fulminating hepatitis after treatment with naproxen and/or disulfiram?]. / Fulminant hepatitt etter behandling med naproxen og/eller disulfiram?

A 49 year old female was started on disulfiram. Six weeks later she was given naproxen because of epicondylitis. After 5 days' treatment with naproxen she complained of nausea, anorexia and jaundice. At admission, bilirubin was 452 mumol/l, aspartate aminotransferase (ASAT) 1925 U/I, alanine aminotransferase (ALAT) 2815 U/I and prothrombin time measured as Normotest was 27%. The patient developed a fulminant hepatitis and died in hepatic coma almost four weeks after the introduction of naproxen. Postmortem examination disclosed a small liver (1,100 g) and histological examination showed massive necrosis and collapse of the lobules. The naproxen was the most probable cause of death, but it is impossible to exclude disulfiram as causative agent.

[Ulcerative colitis. Complications and sequelae in relation to the extent of the disease. A 10-year material]. / Ulcerøs kolitt. Komplikasjoner og følgetilstander i relasjon til utbredelse. Et tiårsmateriale.

Patients with ulcerative colitis in our catchment area were followed over a ten-years period with the focus on the relation between the extent of inflammation and complications. Total colitis was found in 180 out of 334 patients with known extension, while in 154 of the patients the inflammation was classified as left-sided colitis. The frequency of severe colitis, colectomy and cancer was more or less the same as stated in earlier reports. We observed a difference, however, between the patients with extensive colitis and those with left-sided colitis as regards the course of the disease and the complications related to ulcerative colitis. The risk of liver disease, severe colitis and colectomy were significantly higher among the patients suffering from extensive colitis. Extraintestinal manifestations, on the other hand, were equally distributed among both groups of patients. The reasons for the observed differences are unknown.

Treatment of mercuric chloride poisoning with dimercaptosuccinic acid and diuretics: preliminary studies.

The distribution and excretion of mercury were studied in mice given a single injection of HgCl2 with or without chelation treatment. DMS (2,3-dimercaptosuccinic acid) given intravenously (0.5 mmol SH/kg) to mice 24 h after the mercury injection reduced the kidney Hg level significantly, while NAPA (N-acetyl-DL-penicillamine) and BAL (2,3-dimercaptopropanol) did not. The effectivity of DMS to remove Hg from kidneys was comparable to that of BAL-sulph (2,3-dimercaptopropane-1-sulfonate), irrespective of whether these chelating agents were given orally or intravenously. Immediate chelation treatment with DMS or mercaptodextran reduced the renal Hg level to about 50% of control levels, as measured 3 d after the treatment. Combination of DMS with immediate intraperitoneal treatment with spironolactone was even more effective in reducing the renal levels, and acted both by increasing the fecal and urinary excretion. The DMS treatment, as well as DMS + spironolactone in combination, could protect against kidney damage following injection of 30 mumol HgCl2/kg. Such treatment was essentially nontoxic.

[Gonad function in men with alcoholic liver disease]. / Gonadefunksjonen hos menn med alkoholisk leversykdom.

The connection between alcoholic liver disease and hypogonadism has long been recognized. In this study of 112 males admitted to a medical department, altogether 87 had alcoholic liver disease. Serum testosterone was depressed (less than 12 nmol/l) in 47 out of 51 (92%) patients with alcoholic liver cirrhosis and in 13 out of 36 (36%) with alcoholic fatty liver (p less than 0.001). Primary hypogonadism was found in 8% of the patients with alcoholic fatty liver and in 16% of the patients with alcoholic cirrhosis and secondary hypogonadism in 28% of the patients with fatty liver and in 76% of those with alcoholic cirrhosis. Serum sex hormone binding globulin (SHBG) was increased (greater than 40 nmol/l) in 65% of the patients with fatty liver and in 67% of the patients with alcoholic cirrhosis. Serum testosterone was significantly correlated to liver function tests Normotest (NT), bilirubin and albumin. In conclusion, hypogonadism is very common in men with alcoholic liver disease.

Serum ferritin and transferrin saturation in patients with chronic alcoholic and non-alcoholic liver diseases.

OBJECTIVES: To compare serum ferritin concentration and transferrin saturation in patients with alcoholic and non-alcoholic chronic liver diseases. DESIGN: Consecutive patients with liver diseases. SETTING: The department of internal medicine in a teaching hospital. SUBJECTS: Three hundred and twelve patients with different liver diseases consecutively admitted between 1987 and 1992. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Fasting serum iron, transferrin and ferritin. RESULTS: Serum ferritin was increased above 200 micrograms L-1 in all 18 patients with haemochromatosis (range 310-6500 micrograms L-1), in 64 of 111 alcoholics (58%) and in 30 of 137 (22%) with chronic non-alcoholic liver diseases (P < 0.01). Twelve of 111 alcoholics (11%) had serum ferritin above 1000 micrograms L-1 compared with one of 137 (0.7%) with chronic non-alcoholic liver diseases. In 13 alcoholics who abstained after admission, serum ferritin decreased from 1483 micrograms L1 +/- 1134 to 388 micrograms L-1 +/- 237 (P < 0.001) after 1 1/2 to 6 weeks. The transferrin saturation was increased above 62% in 13 of 18 patients (72%) with haemochromatosis, in 16 of 105 alcoholics (15.2%) and in three of 132 (2.3%) with chronic non-alcoholic liver disease (P < 0.01). CONCLUSION: Serum ferritin is more frequently elevated in abusing patients with alcoholic liver disease than in patients with other chronic liver diseases such as autoimmune liver diseases and hepatitis C. Because serum ferritin decreases rapidly during abstinence, the measurement of ferritin for the detection of haemochromatosis in patients abusing alcohol should be postponed until the patients are abstaining. Most of the patients with increased serum ferritin have normal transferrin saturation values which can be used to separate them from haemochromatosis.

[Computer tomography in the detection of hemochromatosis]. / Computertomografi til påvisning av hemokromatose.

Computed tomography (CT) was performed to estimate the density of the hepatic and splenic parenchyma in 18 patients with hemochromatosis. The mean CT density was 79 +/- 21 Hounsfield units compared with 61 +/- 9 (p < 0.01) in 31 controls without hepatic disease. Increased density above 79 Hounsfield units was found in eight patients out of 18 (44%). The highest density (125 Hounsfield units) was found in a patient with a serum ferritin of 6500 micrograms/l. There was an association between CT density and serum ferritin (r = 0.72, p < 0.01). The difference in density between liver and spleen gave better discrimination between patients and controls: 12 of 18 (67%) showed an increased difference in density between liver and spleen. We conclude that CT represents a non-invasive alternative to liver biopsy in cases where the latter is contraindicated. However, CT is not sensitive when serum ferritin is below 1,000 micrograms/l.

The Cronkhite-Canada syndrome. Case report.

Polyps of the stomach, duodenum, colon and rectum were found in a 53-year-old man, who had severe diarrhoea, heavy protein loss from the gastrointestinal tract and shedding of hair and nails. The patient died after 9 months of treatment with drugs and periodic intravenous nutrition.

Massive ascites as a complication to subclinical perihepatitis and pelvic inflammatory disease.

A case report is presented of a 16-year old female who had a history of abdominal distention due to 5,000 ml ascites as a serious complication of pelvic inflammatory disease. She made an uneventful recovery after exploratory laparotomy and removal of the right inflamed and dilated Fallopian tube.

Protein C in patients with alcoholic cirrhosis and other liver diseases.

The coagulation inhibitor protein C was measured in 151 patients with various liver diseases. The protein C level was significantly decreased in patients with alcoholic cirrhosis (n = 73) compared to patients with steatosis (n = 24) (40 +/- 2%) vs. 88 +/- 4%, mean S.E., p less than 0.001). It was also decreased in cases of acute liver damage (n = 8) and in patients with non-alcoholic cirrhosis (n = 15) (35 +/- 7% and 36 +/- 4%, respectively). A significant correlation was found between protein C and Normotest, antithrombin, heparin cofactor II, (r = 0.83, r = 0.82, r = 0.81, respectively, p less than 0.001). There was also a significant correlation between protein C and serum concentrations of albumin (r = 0.61, p less than 0.001), but a negative association to bilirubin (r = -0.56). No significant association was found between protein C and aspartate aminotransferase, alaline aminotransferase, and gamma-glutamyltranspeptidase. In conclusion, protein C is low in advanced liver diseases and gives the same amount and type of information as Normotest, antithrombin and heparin cofactor II.

[Carbamazepine-induced hepatitis]. / Karbamazepinindusert hepatitt.

BACKGROUND: Hepatotoxic reactions associated with carbamazepine therapy are well recognised, and it is important that clinicians are aware of this adverse effect. MATERIAL AND METHODS: We present the clinical course in three patients with carbamazepine-induced hepatitis. RESULTS: All three patients had clinical and biochemical signs of hepatitis; improvement occurred immediately after carbamazepine therapy was discontinued. Other causes of hepatitis were excluded. INTERPRETATION: Previous reports concerning this adverse effect are reviewed. Focusing on the liver as the major organ for drug metabolism, we discuss possible pathophysiological mechanisms of drug-induced hepatic injury. A thorough medication history is mandatory in all patients with hepatitis and other liver diseases. The prognosis of carbamazepine-induced hepatitis is usually excellent, but fatal cases have been reported.

Serum procollagen III peptide in alcoholic and other chronic liver diseases.

Increased levels of serum procollagen III peptide (P-III-P) have been found in patients with alcoholic hepatitis and cirrhosis. Serum P-III-P was increased (greater than 15 micrograms/l) in 38 of 44 (86%) patients with alcoholic liver cirrhosis, in 6 of 20 (30%) with fatty liver, in 1 of 13 (8%) with non-alcoholic fatty liver, and in 3 of 14 (21%) with other chronic liver diseases. Median serum P-III-P was almost three times higher in alcoholic liver cirrhosis than in alcoholic fatty liver (p less than 0.001). Serum P-III-P was increased in three of six patients with alcoholic fatty liver and periportal fibrosis. In the total material (n = 91), a statistically significant negative correlation between serum P-III-P and albumin (r = -0.71, p less than 0.001) and Normotest (r = -0.63, p less than 0.001), respectively, and a positive correlation between serum P-III-P and bilirubin (r = 0.65, p less than 0.001) were found. The serum level of P-III-P had no prognostic value concerning the mortality in patients with alcoholic cirrhosis.

Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein.

This study comprised 62 outpatients with ulcerative colitis who underwent 64 colonoscopies. The disease activity was evaluated according to endoscopic and histological criteria. The results revealed a significant correlation between both the endoscopic as well as the histological gradings of disease activity and faecal calprotectin. The median faecal calprotectin levels in the control group (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were significantly different (p < 0.0001). The median calprotectin level among patients with active disease was 68 mg/l which was significantly different from the latter group (p < 0.0001). Furthermore, we suggest that the degree of inflammation rather than the extent of the disease determined the faecal calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be a marker of disease activity in patients with ulcerative colitis.

[Non-alcoholic steatohepatitis]. / Ikke-alkoholisk steatohepatitt.

BACKGROUND: There is a growing interest in nonalcoholic steatohepatitis (NASH), a disease entity which is quite similar to alcoholic liver disease. MATERIAL AND METHODS: We present three patients with nonalcoholic steatohepatitis, and review current opinion on this disease entity. RESULTS: Non-alcoholic steatohepatitis is very often associated with the insulin resistance syndrome. There is also an association with hepatic iron overload. In one of our patients, biochemical improvement occurred after treatment with phlebotomy. Insulin resistance, resulting in fat accumulation, seems to be an important first step in the pathogenesis. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage. In some patients, these events result in necroinflammation mediated by various cytokines and immunoactive cells. The prognosis in pure steatosis is usually good. Presence of necroinflammation or fibrosis indicates a risk of progressive liver disease, including cirrhosis.

[Primary sclerosing cholangitis. Illustrated by an unselected hospital material]. / Primaer skleroserende kolangitt. Belyst i et uselektert sykehusmateriale.

During the period from 1985 to 1993 primary sclerosing cholangitis was diagnosed in 16 patients, five females and 11 males, mean age 43 years. 12 of the patients (75%) had inflammatory bowel disease. Among 262 patients with ulcerative colitis, cholangitis was found in ten, whereas the disease was diagnosed in only two (1.9%) of the 108 patients with Crohn's disease. In eight patients (50%) no progression of the cholangitis was observed. However, six patients (38%) died during the observation period, three 19% due to cholangiocarcinoma and one due to liver failure. Cholangiocarcinoma is frequently found in patients with primary sclerosing cholangitis. A mortality of 38% indicates a serious clinical course in many patients.

[Clinical experience with early hemochromatosis]. / Klinisk erfaring med tidlig hemokromatose.

During the period 1986-93 22 patients were diagnosed as having primary hemochromatosis. Only 11 of them had elevated aminotransferases. Transferrin saturation was higher > 63% in 17 (77%) and serum-ferritin was higher in all the patients. (257 mumol/l to 6,500 mumol/l). A percutaneous liver biopsy was performed in 20 patients, all of whom showed a characteristic grading from 2 + to 4+ using Perls' stain. Two males had cirrhosis with simultaneous hepatocellular carcinoma, and another two had cirrhosis. One patient had diabetes mellitus type I. We conclude that fasting serum-iron and transferrin should be determined in all subjects over 40 years of age and in patients with chronic elevation of liver enzymes. If transferrin saturation is higher than 50% in females and 60% in males, serum ferritin should be determined. A percutaneous liver biopsy should be performed if both values are higher than normal. Screening of siblings is important because of the autosomal recessive pattern of inheritance.

Long-term prognosis of patients with alcoholic liver cirrhosis: a 15-year follow-up study of 100 Norwegian patients admitted to one unit.

BACKGROUND: Most follow-up studies in patients with alcoholic liver cirrhosis have been for a 5-year period or less. The aim of this study was to assess the long-term mortality and causes of death among patients with alcoholic liver cirrhosis and to identify predictors of mortality. METHODS: One hundred patients with alcoholic liver cirrhosis, consecutively admitted to one medical department, were included in the study from May 1984 until December 1988. All patients had a history of alcohol abuse of at least 100 g ethanol daily for several years. The study comprised 65 men and 35 women with a median age of 58 years (range 34-82). Percutaneous liver biopsies and/or autopsies were obtained on 89 patients. Sixty-seven had ascites at admission and 34% had bleeding oesophageal varices. All patients were followed prospectively until death or until October 2000. RESULTS: During the follow-up period 90% of the patients died, 68 of whom (76 %) had been autopsied. The cumulative actuarial mortality after 1, 3, 6 and 12 months was 18%, 28%, 36% and 49%, respectively and after 5, 10 and 15 years 71%, 84% and 90%, respectively. None of the patients underwent liver transplantation during the study. The causes of death were bleeding, liver failure or a combination of these two conditions in 52 of 90 patients (58%), while 9 (11%) died of hepatocellular carcinoma 0.5 to 73 months after inclusion in the study. Using the Cox regression analysis, age, alcohol abuse and alkaline phosphatase were independent and significant predictors of mortality, but Child-Pugh class was not. CONCLUSIONS: The mortality in a group of patients with advanced alcoholic cirrhosis was extremely high with 5 and 15 years' mortality in 71% and 90%, respectively. Independent predictors of a poor prognosis were high age, continuous alcohol consumption of more than 10 g ethanol per day and high levels of alkaline phosphatase.

Hepatitis C in the general adult population of Oslo: prevalence and clinical spectrum.

BACKGROUND: The prevalence of hepatitis C (HCV) in Northern Europe has not been well described. This study aimed to estimate the prevalence and spectrum of hepatitis C infection in the general adult population of Oslo, Norway. METHODS: The study was part of the Oslo Health Study 2000-2001 and included a random selection of individuals older than 30 years living in Oslo County. Sera from 11,456 participants were screened for anti-HCV (EIA-3), positive samples were confirmed (RIBA-3) and examined for HCV RNA (PCR). All anti-HCV positive patients were offered clinical evaluation. Routine biochemical liver tests were performed. Candidates for HCV treatment were asked to undergo a percutanous liver biopsy. RESULTS: Among 11,456 participants HCV RNA was detected in 62 (0.5%) and HCV RNA with raised serum alanine aminotransferase (ALT) in 46 (0.4%). Anti-HCV was detected in 78 (0.7%) with a peak prevalence of 1.5% among subjects 40 and 45 years old. Being anti-HCV positive was associated with being unmarried, unemployed and having low education. Anti-HCV prevalence was higher among subjects with alcohol-related problems compared to those without (4.4% versus 0.6%, P < 0.001). It was also higher among smokers compared to non-smokers (2.0% versus 0.2%, P < 0.001). In 33 liver biopsies, bridging fibrosis was seen in 8 (24%) and cirrhosis in 1 (3%). The route of transmission was injecting drug use in 67%, transfusion in 6% and unknown in 27%. CONCLUSION: In this population-based survey the prevalence of chronic hepatitis C was 0.5% and ALT was raised in 80% of those with chronic infection.