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Biomedical subjects

R Hultcrantz

Publications and source records attributed to R Hultcrantz.

At least 73 records · Page 4Linked to original sources
PubMed1993

Patients with persistent elevation of aminotransferases: investigation with ultrasonography, radionuclide imaging and liver biopsy.

Eighty-three patients, submitted for investigation of the liver due to persistently elevated activities of serum aminotransferases were included in a study in order to compare the relative merits of liver biopsy, ultrasound and radionuclide imaging. From the liver biopsy it was found that 45 patients had fatty liver, 14 had cirrhosis and 11 had chronic inflammation, 3 had haemochromatosis and 10 had unspecific changes or normal findings. An investigation with ultrasound yielded pathological findings in 65% of the patients. The sensitivity was highest in patients with fatty liver (82%) and more than 10% fat in the liver always resulted in increased echogenicity. Alterations in the liver due to cirrhosis and chronic inflammation were detected with ultrasound in only 50% and 57% of the cases, respectively. Radionuclide imaging was positive in 44% of the patients with fatty liver. 64% of those with cirrhosis and 21% of the patients with chronic inflammation. It was only possible to distinguish fatty liver from cirrhosis in those patients who had an increase in the size of the spleen (four patients). The study demonstrates that in patients with a persistent elevation of serum aminotransferases ultrasound has a high sensitivity for detecting more than 10% fat in the liver. However, both the ultrasound and a liver scintigram had a rather low sensitivity and a very low specificity for making a diagnosis for this group of patients. With the aid of a liver biopsy it was possible to establish a diagnosis in 90% of the patients.

Adult↗
PubMed1993

Lack of concomitant expression of ICAM-1 and HLA-DR on bile duct cells from patients with primary sclerosing cholangitis and primary biliary cirrhosis.

In both primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) prominent infiltrates of lymphocytes surround the bile ducts, on which an abberrant expression of major histocompatibility complex class II antigens has been found, suggesting that the immune system is involved in the biliary destruction. Since the lymphocytes presumably must adhere to the bile ducts to initiate a cell-to-cell-mediated destruction, we have studied the expression of the lymphocyte function-associated antigen-1 (LFA-1) together with its ligand, the intercellular adhesion molecule-1 (ICAM-1), and the expression of HLA-DR, using immunoperoxidase staining of cryostat sections from patients with PBC (n = 10), PSC (n = 13), and normal healthy controls (n = 6). Most lymphocytes expressed LFA-1. ICAM-1 expression was found on hepatocytes from 9 of 10 PBC and 10 of 13 PSC patients but was not seen on hepatocytes from the controls. Hepatocytes expressing HLA-DR were only found in one patient with PBC. None of the septal bile ducts expressed ICAM-1, and only one PSC patient and three PBC patients expressed ICAM-1 on their interlobular bile ducts. The bile ducts in 22 of 23 patients, however, expressed HLA-DR. Proliferating bile ductules from two PBC patients and three PSC patients showed a concomitant expression of ICAM-1 and HLA-DR. None of the bile ducts from the controls expressed ICAM-1 or HLA-DR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Growth-regulatory effects of sensory neuropeptides, epidermal growth factor, insulin, and somatostatin on the non-transformed intestinal epithelial cell line IEC-6 and the colon cancer cell line HT 29.

A non-transformed small-intestinal cell line from the rat (IEC-6) and a human colon cancer cell line (HT 29) were examined for their trophic response to sensory neuropeptides. Substance P, neurokinin A (NKA), calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), and peptide YY (PYY) were tested. Epidermal growth factor (EGF), insulin, and somatostatin-14 were also used. Interaction studies were performed on IEC-6 cells by combining EGF or insulin with somatostatin-14. The sensory neuropeptides had no effect either on IEC-6 cell growth and DNA synthesis or on HT29 cell growth. EGF and insulin stimulated cell growth and DNA synthesis in IEC-6 cells and cell growth in HT 29 cells in a dose-dependent fashion. Somatostatin-14 had no effect either alone or in combination with EGF or insulin on IEC-6 cell growth and DNA synthesis. HT 29 cell growth was inhibited by somatostatin-14 only in the presence of serum with a maximal and significant response at 10(-7) M. Our observations suggest that the sensory neuropeptides do not exert a direct growth-regulatory effect either on IEC-6 cells or on HT 29 cells. Somatostatin, however, inhibits serum-induced HT 29 cell growth but does not interfere directly with the proliferative effect of serum, EGF, or insulin on IEC-6 cells in this model.

Animals↗
PubMed1992

Rectal cancer risk in patients treated for familial adenomatous polyposis. The Leeds Castle Polyposis Group.

Total colectomy with ileorectal anastomosis (IRA) in familial adenomatous polyposis (FAP) leaves patients at risk for rectal cancer. To assess this risk, the rectal cancer incidence in 297 patients with FAP undergoing IRA since 1951 was determined in the population-based registers of Denmark, Finland and Sweden. At the same time, detailed data on 50 patients with FAP and invasive rectal cancer were obtained from 11 international polyposis registries. The cumulative incidence of rectal cancer was 13.1 per cent at 25 years. The 5-year survival rate of patients with FAP developing rectal cancer was 71 per cent. Combining both studies, the risk of dying from rectal cancer after IRA was 2.0 per cent at 15 years of follow-up. These results justify IRA as primary treatment for most patients; restorative proctocolectomy is preferred for some subgroups. The high all-cause mortality rate observed in this relatively young population necessitates lifelong surveillance of patients with FAP.

Adenomatous Polyposis Coli↗
PubMed1992

Bile-duct destruction and collagen deposition: a prominent ultrastructural feature of the liver in cystic fibrosis.

To study the liver disease of patients with cystic fibrosis, percutaneous liver biopsies were performed in 10 patients with cystic fibrosis aged 6 to 22 yr. Nine of 10 patients had high Shwachman scores, eight had normal serum levels of transaminases. Light-microscopical examination showed steatosis in seven cases and in five slight or moderate inflammatory infiltration. Eight patients showed varying degrees of fibrosis and even cirrhosis. Six patients had bile-duct proliferation and, in one case a bile plug was found. Other signs of cholestasis were not seen. Electron-microscopical investigation showed no specific signs of cholestasis such as ductal plugs or intracellular bile pigments. The canaliculi were not dilated, except in one case. Most patients had bile-duct cells with irregular shapes, protruding into the lumen, and some cases even had necrotic cells. Around the bile ducts and ductules, collagen was deposited and fat-storing cells were a common finding. Our findings do not support the view that cholestasis is the pathogenetic factor in liver disease in cystic fibrosis. A cytotoxic influence on the biliary cells, stimulating collagen deposition, seems more likely.

Adolescent↗
PubMed1992

Liver damage from flucloxacillin, cloxacillin and dicloxacillin.

We describe a case of severe cholestatic liver disease, which persisted for 7 years, and was probably induced by flucloxacillin. We also report a survey of 77 liver reactions which were probably or possibly induced by penicillinase-resistant penicillins and spontaneously reported to the Swedish Adverse Drug Reactions Advisory Committee. The reactions were usually cholestatic with a tendency to a protracted course. There is some evidence for an immunoallergic idiosyncratic reaction. The incidence of reported liver reactions was estimated from sales data to be 1.6-2.9 per million DDD (defined daily doses) or, for flucloxacillin 1:11,000-1:30,000 prescriptions. Female sex, age and high daily doses seemed to be associated with higher risk of liver reactions from flucloxacillin.

Chemical and Drug Induced Liver Injury↗
PubMed1991

Iron mediates production of a neutrophil chemoattractant by rat hepatocytes metabolizing ethanol.

Ethanol metabolism in hepatocytes is accompanied by release of a potent lipid chemoattractant for neutrophils. Production of the factor may initiate the inflammation associated with alcoholic hepatitis. In previous studies with a cytosol system from liver, production was blocked by iron chelators as well as by catalase and superoxide dismutase, suggesting the involvement of oxyradicals in formation of the chemoattractant. These studies have examined the role of iron in intact hepatocytes using cells from rats fed an iron-deficient diet, a control diet or a diet containing 3% carbonyl iron. The iron content averaged 1.4 nmol/mg protein in iron-deficient cells, 6.3 in controls and 135.3 in iron-loaded cells. Hepatocytes from all groups were established in primary culture and incubated with ethanol (10 mM); the medium was assayed for chemoattractant activity for human neutrophils. Cultures from chow-fed or iron-loaded animals produced chemoattractant as previously reported. By contrast, chemoattractant production was undetectable in the iron-deficient cultures. Addition of ferric citrate (10 microM) restored chemoattractant production while increasing cellular iron in the deficient cells less than 50% (to 2.3 nmol/mg protein). Addition of desferrioxamine mesylate to cultures of iron-loaded cells ablated chemoattractant production. The data provide evidence for the importance of hepatocellular iron in production of this alcohol-related lipid chemoattractant and suggest that a small intracellular pool of "free" iron plays a critical role.

Animals↗
PubMed1990

Liver cell damage and lysosomal iron storage in patients with idiopathic hemochromatosis. A light and electron microscopic study.

Eleven patients with idiopathic hemochromatosis were subjected to percutaneous liver biopsy, and seven were rebiopsied after repeated phlebotomies. The liver tissue was examined by light and electron microscopy. Ultrastructural morphometry was also performed and iron content was determined. Initially, all biopsies displayed large iron-laden lysosomes in the hepatocytes. Lysosomal volume density was increased and correlated well with liver iron content (r = 0.84, p less than 0.005). Neither mitochondria nor the endoplasmic reticulum showed any ultrastructural changes, except in the necrotic cells of biopsies with the highest liver iron content. In these cases, iron-laden lysosomes were also encountered in the Kupffer cells. Following treatment, liver iron content and lysosomal volume density were normalized. More specifically, iron content was 14.1 +/- 2.1 micrograms Fe/mg protein before and 1.3 +/- 0.3 micrograms Fe/mg protein after treatment (p less than 0.001). Lysosomal volume density was 6.1 +/- 0.8% before and 1.8 +/- 0.2% after treatment (p less than 0.001). Hence, in the precirrhotic stage of idiopathic hemochromatosis, the first evident ultrastructural changes are in the lysosomal compartment. These changes correlate well with the iron overload, also in advanced stages of the disease, and are reversed after iron removal.

Adult↗
PubMed1990

Increased turnover of very low density lipoprotein triglyceride during treatment with cholestyramine in familial hypercholesterolaemia.

Kinetics of very low density lipoprotein (VLDL) triglyceride were determined in seven patients with heterozygous familial hypercholesterolaemia, using a 3H-glycerol technique. The study was repeated after 5-7 weeks of therapy with the bile acid-binding resin, cholestyramine. The rate of synthesis of VLDL triglyceride was increased by 85% (P less than 0.05) during resin therapy. Simultaneously, the fractional catabolic rate of VLDL was increased by 40% (P less than 0.02), so that only a moderate increase in plasma concentration was observed. Repeated measurements of VLDL size by electron microscopy (before, 1 week, and 5-7 weeks after initiation of therapy) indicated that a transient increase in VLDL size occurred in response to cholestyramine. The results are consistent with a stimulatory effect of bile acid sequestrants on VLDL triglyceride production and indicate that, in most subjects, a compensatory increase in VLDL triglyceride removal occurs.

Adult↗
PubMed1990

Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests.

Hepatobiliary disorders are well known complications in patients with ulcerative colitis but it is not possible to predict those patients with ulcerative colitis who will eventually develop liver disease. In this study, liver biopsies from 74 patients with ulcerative colitis have been reevaluated. None of the patients showed clinical or biochemical signs of liver disease at the time of biopsy. Thirty seven (50%) had a completely normal liver biopsy. The others showed minimal portal inflammation or fatty infiltration. The biopsies of three patients displayed concentric, periductular fibrosis, or so called 'onion skin' lesions. None showed other signs of fibrosis or cirrhosis. The histological findings were unrelated to either activity or extent of colitis, except for the onion skin lesions which were seen exclusively in biopsies of patients with involvement of the total colon. Sixty eight of the 74 patients were reviewed after a mean interval of 18 years. The majority had no symptoms of hepatobiliary disorders and only two had developed liver disease; one suffered from cryptogenic cirrhosis, possibly due to non-A, non-B hepatitis and the other of an autoimmune liver disease and later developed a bile duct carcinoma. Both were women with total colonic involvement. At the time of the first liver biopsy one showed no histological abnormalities and the other only minor fatty infiltration. Thus, minor abnormalities in liver tissue are common in patients with ulcerative colitis without biochemical evidence of liver disease. The morphological changes are of little help in predicting the future risk of a patient with ulcerative colitis developing a clinically relevant hepatobiliary complication. The absence of biochemical parameters for liver disease during the early years of ulcerative colitis predict a favourable longterm diagnosis as regards hepatobiliary complications.

Adolescent↗
PubMed1990

Studies with the haeme oxygenase inhibitor Sn-protoporphyrin in patients with primary biliary cirrhosis and idiopathic haemochromatosis.

Sn(tin4+)-protoporphyrin, a potent competitive inhibitor of haeme oxygenase, the rate limiting enzyme in the degradation of haeme to bile pigments, was given intravenously to six patients with primary biliary cirrhosis and to four patients with idiopathic haemochromatosis. Serum bilirubin concentrations decreased in all patients after administration of 1-2 mumol/kg body weight of the metalloporphyrin, given in two doses eight to 24 hours apart. This reduction lasted approximately four to five days after injection of the compound. Excretion of endogenous haeme in bile increased (mean increase approximately two to threefold) in parallel with the decrease in serum bilirubin concentrations in both patient groups, and the highest biliary haeme concentrations were found during the first 48 hours after treatment. Sn-protoporphyrin was cleared rapidly from plasma with a half-life of 3.4 hours. Biliary bilirubin concentrations decreased (mean decrease, 49%) in the haemochromatosis patients after Sn-protoporphyrin administration. No decrease in biliary bilirubin concentrations could be detected in the primary biliary cirrhosis patients under the same conditions. Thus, Sn-protoporphyrin treatment resulted in a decrease in serum bilirubin concentrations and an increase in biliary haeme excretion in patients with haemochromatosis and primary biliary cirrhosis, as has previously been shown in normal subjects. The results indicate that the synthetic haeme analogue inhibits haeme oxidation activity in the two patient groups studied, as it does in normal people and in experimental animals. The lack of effect of Sn-protoporphyrin on biliary bilirubin excretion in primary biliary cirrhosis may be related to a differently affected hepatic clearance system or to a different distribution of tissue bilirubin pools in this condition.

Adult↗
PubMed1990

Distribution of HLA-DR, HLA-DP, HLA-DQ antigens in liver tissue from patients with primary sclerosing cholangitis.

This study describes the distribution of the major histocompatibility class II antigens HLA-DR, HLA-DP, and HLA-DQ in liver tissue from eight patients with primary sclerosing cholangitis, by means of the immunoperoxidase technique on cut cryostat sections. HLA-DR was expressed on the bile duct epithelium and vascular endothelium from all patients. HLA-DP showed an expression much like HLA-DR on the bile duct epithelium, but the vascular endothelium mostly did not stain for HLA-DP. HLA-DQ was generally more weakly expressed, and only three of the patients expressed HLA-DQ on the bile ducts. None of the hepatocytes expressed any of the MHC class II antigens.

Adult↗
PubMed1989

Biliary excretion of iron and ferritin in idiopathic hemochromatosis.

The role of biliary excretion of iron and ferritin in iron overload was studied and evaluated. Ten patients with idiopathic hemochromatosis and two groups of controls (14 gallstone patients and 16 healthy subjects) were included. Liver tissue (obtained by percutaneous or operative biopsy) was investigated with light microscopy and transmission electron microscopy in combination with x-ray microanalysis. Fasting bile samples were obtained through duodenal aspiration or at cholecystectomy. Iron was determined in liver tissue and bile using atomic absorption spectroscopy, and ferritin was determined in serum and bile with a radioimmunoassay technique. All patients with hemochromatosis had iron-positive staining as seen in light microscopy. Electron microscopy showed iron-containing proteins in the lysosomes and cytosol of liver parenchymal cells, and this observation was supported by x-ray microanalysis. Hepatic iron concentration was increased about eightfold in the patients with hemochromatosis (p less than 0.001). Biliary iron concentration, expressed per millimole of bile acid, was increased about twofold (p less than 0.05) and biliary ferritin concentration about fivefold (p less than 0.001) in hemochromatosis. Four of the patients with hemochromatosis were reexamined after completed treatment with venesection; this resulted in normalized biliary concentrations of iron and ferritin. We conclude that biliary secretion of ferritin occurs in humans and that both iron and ferritin excretion are enhanced in hepatic iron overload. The apparently limited capacity of biliary iron excretion may be of importance for the hepatic iron accumulation in hemochromatosis.

Adult↗
PubMed1989

Prevalence of a haemochromatosis among men with clinically significant bradyarrhythmias.

Cardiac involvement in haemochromatosis includes development of congestive heart failure and/or cardiac arrhythmias. To elucidate the importance of this disorder among patients with severe cardiac bradyarrhythmias necessitating treatment with a permanent pacemaker, such patients were screened for evidence of iron overload. Serum ferritin was determined in 232 men treated with a permanent pacemaker. In six patients (2.6%) the serum ferritin values were twice the upper normal limit. In three of these, causes other than iron overload were found (liver cancer, myeloma and amiodarone treatment), while in three (1.3%) iron overload was suspected. All the latter three had atrioventricular block of second to third degree. In these patients percutaneous liver biopsy was performed. The specimens were examined by light and electron microscopy and the iron content was determined by atomic absorption spectrophotometry. The results of these investigations showed iron overload in the liver. The prevalence of iron overload (2.0%) among this male pacemaker-treated population with AV block II-III is significantly higher than the rates previously found in urban populations in Sweden. The present data indicate that screening for haemochromatosis is of importance among males with second and third degree atrioventricular-block of unknown etiology.

Bradycardia↗
PubMed1989

The source of serum alkaline phosphatases in liver-tumour-bearing rats.

Patients with hepatic tumours have increased serum activities of alkaline phosphatases. In order to clarify the origin of the increased enzyme activity, two experimental models of rat liver carcinogenesis were studied. In one model, the resistant hepatocyte model, the process was initiated by diethylnitrosamine (DEN, 200 mg/kg), and preneoplastic liver nodules were selected for by 2 weeks of 2-acetylaminofluorene (2-AAF, 0.02%) feeding and partial hepatectomy (PH). High activities of serum alkaline phosphatases were found in these rapidly growing nodules harvested at the peak time of nodular mass expansion. In the other model in which nodules were induced with long-term intermittent feeding of a diet containing 0.05% 2-AAF and harvested in a late stage with a low increase of nodular liver cell mass, no such increase in serum alkaline phosphatase activity was found. A similar difference was also noted when measuring the activities of the enzyme in the nodular tissue. Thus the first model showed high activities of the enzyme in the nodular tissue, while the second model had similar activities to those of the control animals. The serum levels reflected the nodular enzyme activity in both models. The tissue surrounding the nodules did not show increased enzyme activity. No difference was noted in the serum or tissue activity of transaminases. In both models the liver nodules occupied 30-50% of the liver volume. The experimental models were selected to emphasize the importance of the rate of intrahepatic mass expansion for the levels of serum alkaline phosphatase activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗