Search PubMed⌕ Search

Biomedical subjects

P Christoffersen

Publications and source records attributed to P Christoffersen.

At least 55 records · Page 3Linked to original sources

Early alcoholic liver injury. Activation of lipocytes in acinar zone 3 and correlation to degree of collagen formation in the Disse space.

Acinar zone 3 areas in liver biopsy specimens from 23 alcoholics and 47 non-alcoholics were investigated by light microscopy and transmission electron microscopy to asses fibrosis in the perisinusoidal space and to evaluate the role of the lipocytes. Quantitative analysis by light microscopy on toluidine blue-stained sections showed a significant reduction in number of lipocytes--median values of 2.7 and 1.2 lipocytes per 100 hepatocytes in biopsies from chronic alcoholics showing no or varying degrees of zone 3 fibrosis, respectively, as compared to 3.6 lipocytes per 100 hepatocytes in non-alcoholic livers. By transmission electron microscopy, the reduction in number of lipocytes was related to a corresponding increase in number of cells rich in rough endoplasmic reticulum and microfilaments (activated lipocytes). The occurrence of activated cells was significantly correlated to fibrosis of the perisinusoidal space. Activation of lipocytes and collagenization of the perisinusoidal space appeared before light microscopic evidence of fibrosis and were topographically not related to Mallory bodies or alcoholic hepatitis.

Actin Cytoskeleton↗

Perfusion fixation of hepatic needle biopsies for scanning electron microscopy. A methodological study.

Perfusion fixation is essential for the examination of the hepatic microvasculature by scanning electron microscopy. No detailed study has previously been done on the perfusion of human hepatic needle biopsies. The present paper demonstrates two modifications of a simple technique by which needle biopsies can be perfused. Perfusion was performed either manually (n = 33) or with a constant perfusion pressure of 10-15 mm H2O (n = 54). No significant difference in the ultrastructural preservation was observed in the two groups. Manual perfusion, however, when done gently, was superior in cleaning the sinusoids, and thus larger areas could be investigated by this method. Topographical orientation was possible, allowing the identification of terminal hepatic veins and portal tracts.

Biopsy, Needle↗

The sinusoidal lining cells in "normal" human liver. A scanning electron microscopic investigation.

The scanning electron microscopic was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3 and acinar zone 1 areas. The porosity, i.e. fenestrated area relative to total area of the sinusoidal lining wall, was estimated on micrographs by using a Texture Analysing System (TAS). A zonal gradient was found with median 23.5 fenestrae per micron 2 in zone 3, as compared to 19.2 fenestrae per micron 2 in the zone 1 area (p less than 0.005). Increasing porosity towards the terminal hepatic vein was found (9.1% in zone 3 vs. 7.6% in zone 1 (p less than 0.05)). This was due to an increased number of fenestrae measuring 100 nm or less in diameter in zone 3 areas. The number of fenestrae measuring more than 100 nm but less than 300 nm was unchanged along the sinusoids. Fenestrae larger than 300 nm were rare and randomly distributed. The results suggest a different permeability along the sinusoidal lining, which may influence the transport between blood and hepatocytes and thus be of importance to hepatocellular function.

Adult↗

The blood hepatocytic barrier: a light microscopical, transmission- and scanning electron microscopic study.

The normal blood hepatocytic barrier (BHB), comprised by the endothelial lining cells and the perisinusoidal space, was investigated, and it was concluded that the BHB is a complex structure in which each individual part serves several functions. Immunohistochemical staining for factor VIII showed endothelial lining cells to be positive. By TEM and SEM the endothelial cells were seen to be fenestrated without a basal lamina. They possess numerous endocytotic vesicles. The perisinusoidal space contains the lipocytes and a matrix composed of fibrils, and a microfilamentous to granular material. The nature of these matrix components was poorly analyzable by conventional methods. Lipocytes were visualized by LM in: sections stained with oil red 0 after fixation in Baker's formol-calcium and following post-fixation in dichromate, and toluidine-blue-stained Epon-embedded sections. TEM revealed numerous cytoplasmic processes rich in microfilaments encircling the sinusoids.

Azo Compounds↗

Correlation between liver morphology and haemodynamics in alcoholic liver disease.

In 32 alcoholic patients the degree of hepatic architectural destruction was graded (preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) and related to portal pressure. A significant positive correlation was found between degree of architectural destruction and wedged-to-free hepatic vein pressure (W-FHVP) (p less than 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W-FHVP (p less than 0.01) and between degree of fibrosis and W-FHVP (p less than 0.001). In 22 of the patients, hepatic blood flow (HBF) was measured and in these patients hepatic resistance was calculated (W-FHVP/HBF). A significant positive correlation was found between fibrosis and hepatic resistance (p less than 0.01). Further, hepatic architectural destruction (p less than 0.01) was positively correlated to hepatic resistance. Necrosis, fatty change, occurrence of Mallory bodies or inflammation showed no significant correlation with hepatic resistance. Mean hepatocyte volume was calculated in 29 patients, but no correlation was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance.

Adult↗

Mortality of alcohol abusing men prospectively assessed in relation to history of abuse and degree of liver injury.

A prospective evaluation of mortality in relation to a broad range of alcoholic abuse and biopsy-assessed stage of alcoholic liver injury was carried out by following 315 men admitted to hospital for various medical disorders. During 10-13 years, 184 patients (58%) died, which, according to national mortality statistics, corresponds to a mortality ratio of 3.07. 43% of the excess mortality could be attributed to liver disease. Our results indicate that the alcohol abuse, irrespective of its magnitude and duration, is associated with a rather constant excess mortality and that the occurrence and severity of hepatic injury ranging from normal liver to active cirrhosis is directly associated with a subsequent liver-disease-related excess mortality.

Adult↗

Early alcoholic liver injury: changes of the Disse space in acinar zone 3.

One hundred and twelve consecutive liver biopsies were studied by transmission electron microscopy. In 18 out of 23 biopsies from chronic alcoholics showing preserved architecture by light microscopy, basal laminas were found in acinar zone 3 applied to endothelial cells as well as to hepatocytes. Basal laminas occurred independently of Mallory bodies and lipogranulomas, and were observed even in cases where light microscopy showed no fibrosis in zone 3. In addition to basal laminas, deposition of collagen and defenestration of the endothelial cells were observed. Basal laminas were seen only rarely in biopsies from non-alcoholics. We suggest that basal lamina formation in acinar zone 3 is initiated by changes in the perisinusoidal space and that it may contribute to impaired liver cell function and possibly initiate liver cell necrosis.

Biopsy↗

Prospective evaluation of alcohol abuse and alcoholic liver injury in men as predictors of development of cirrhosis.

258 alcohol-abusing men, free from cirrhosis on primary liver biopsy, were followed for 10-13 years during which cirrhosis developed in 38, corresponding to a rate of 2% per year. The likelihood of cirrhosis developing proved to be independent of duration of abuse and of daily consumption before the primary biopsy. This indicates that the effect of alcohol abuse is not cumulative over time, but rather establishes conditions for the development of cirrhosis. The rate of cirrhosis increased stepwise with degree of steatosis in the primary biopsy, and in those with alcoholic hepatitis was nine times higher than in those with no steatosis. This finding, together with the results on alcohol abuse, indicates that steatosis and alcoholic hepatitis, despite their reversibility, are causally associated with cirrhosis rather than epiphenomena of alcohol abuse. In the alcohol-abusing man, a liver biopsy provides more information than alcoholic history about the likelihood of future cirrhosis.

Alcoholism↗

Spleen and portal lymphnode pathology in fatal drug addiction.

Spleen and portal lymphnode sections from 86 drug addicts submitted for medico-legal autopsy at the Institute of Forensic Medicine in Copenhagen in the year 1979 were studied together with tissue sections from 24 "normal" persons. In 70% of the drug addicts the spleen weight was more than 200 g, and in 71% portal lymphnode hyperplasia was found. Birefringent foreign material was found in spleen tissue of drug addicts in 72% and in portal lymphnode tissue in 44%. Signs of antigen stimulation in both spleen and portal lymphnode tissue evaluated by the number of germinal centre and plasma cells were found in more than 80% of the drug addicts compared with about 20% of the "normal" persons. The results were related to anamnestic information of duration of drug abuse, to the spleen weight, to the occurrence of birefringent material and to the liver changes. Examination of lysozyme and immunoglobulin containing cells using the indirect preoxidase technique was performed in a total of 72 cases of spleen tissue, 59 cases of portal lymphnode tissue from drug addicts, 24 cases of spleen tissue and 18 of portal lymphnode tissue from "normal" persons. Lysozyme, IgM and IgG containing cells were found significantly more often among drug addicts than "normal" persons. The results indicate that the splenomegalia and the portal lymphnode hyperplasia often found in drug addicts are caused by continuous antigen stimulation due to repeated injections of various antigens.

Adolescent↗

Occurrence and significance of Mallory bodies in morbidly obese patients. An immunohistochemical study.

Liver biopsies from 61 consecutive patients with morbid obesity (less than 60% overweight) and from 48 patients with alcoholic liver disease were examined for the presence of Mallory bodies. For the detection both routine haematoxylin and eosin stained sections and sections exposed to an immunohistochemical technique were employed. The latter uses an antiserum which recognizes antigenic determinants in Mallory bodies. Using haematoxylin and eosin staining. Mallory bodies were not detected in any of the biopsies from the obese patients, but found to be present in 63% of the patients with alcoholic liver disease. Using the immunohistochemical technique, Mallory bodies were found in the liver of 2 obese patients (3%) and in 36 patients with alcoholic liver disease (75%). None of the Mallory body positive obese patients showed signs of diabetes mellitus, cholestasis or hypocholesterolemia, but both patients admitted previous excessive alcohol consumption. It is concluded that the immunohistochemical detection of Mallory bodies is more sensitive than routine staining. Further, Mallory bodies are rare findings in livers of obese patients and may be related to excessive alcohol consumption.

Adolescent↗

Plasma fibronectin concentrations in morbidly obese patients.

Plasma fibronectin concentrations and liver morphology were investigated in 45 morbidly obese subjects (median overweight 88%) and in 42 normal weight controls, matched for sex and age. A significantly (P less than 0.01) raised plasma fibronectin concentration (median 464 mg/l, range 276-862 mg/l) was found in the obese subjects when compared with concentrations in the controls (median 348 mg/l, range 164-536 mg/l). Plasma fibronectin concentrations of the obese patients correlated significantly to their degree of overweight (r = 0.33, P less than 0.05) as well as to the degree of fatty change found in their liver biopsies (r = 0.33, P less than 0.05). Significantly (P less than 0.05) elevated plasma fibronectin concentrations even in obese subjects without hepatic fatty change indicate that liver fat accumulation is no prerequisite of the obesity-related elevation of plasma fibronectin. Raised plasma fibronectin concentration in obesity may more readily be explained by an increased fibronectin formation by lipocytes.

Adult↗

The liver in consecutive patients with morbid obesity: a clinical, morphological, and biochemical study.

Liver morphology and biochemistry were investigated in 61 morbidly obese subjects selected by defined criteria. Median overweight was 82 per cent (range 61 to 170 per cent), and median duration of overweight was 20 years (range two to 45 years). No patient had more than a moderate alcohol consumption and only one was diabetic. Four biopsies (7 per cent) showed normal liver tissue, while fatty change was the main diagnosis in most cases (85 per cent). Increasing degrees of fatty change was significantly (P less than 0.02) associated with presence of lipogranulomas (found in 54 per cent of the biopsies), focal necroses (found in 28 per cent), slight parenchymal inflammation (found in 33 per cent), and Kupffer cell proliferation (found in 49 per cent). Slight portal inflammation was seen in 23 per cent but portal fibrosis in only 2 per cent of the biopsies. No case of cirrhosis was registered. Patients with moderate or severe fatty change, lipogranulomas , focal necroses or with parenchymal inflammation were significantly more obese than patients without these changes (P less than 0.05). Even in absence of fatty change, obese subjects showed a markedly decreased serum albumin concentration and an elevated serum alkaline phosphatase activity (P less than 0.0001) compared with non-obese controls. Serum lactate dehydrogenase and aspartate aminotransferase were significantly raised only in patients with fatty change. With respect to serum bilirubin and plasma cholesterol concentrations no significant differences were detected between patient subgroups and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

The effect of direct current, sodium hydroxide and hydrochloric acid on pig epidermis. A light microscopic and electron microscopic study.

Lesions in pig skin were induced by direct current, hydrochloric acid and sodium hydroxide, and the morphology of the lesions was compared in order to establish the influence of electrolysis in the electrical lesions. Both light microscopically and electron microscopically a pronounced similarity was found between cathode lesions and base-induced lesions including the presence of vesicular nuclei in both kinds of lesions. Some features were also common to anode lesions and acid induced lesions, but dissimilarities were present as well. From the results it is concluded that electrolysis in the tissue with the subsequent shift of pH, especially towards the alkaline side, is responsible for the formation of the vesicular nuclei which we repeatedly have found to be characteristic of electrical skin lesions. The shift of pH also induces the cytoplasmic feature called "white necrosis" which therefore is found more regularly in electrical lesions than in heat lesions.

Animals↗

Liver histopathology of the hepatitis A virus infection: a comparison with hepatitis type B and non-a, non-b.

Liver biopsies from 86 patients with serologically established acute hepatitis A were evaluated for quantitative and qualitative light microscopic features together with biopsies from 78 patients with acute hepatitis type B and 76 patients with acute hepatitis type non-A, non-B. Hepatitis A was characterised by more pronounced portal inflammation than hepatitis non-A, non-B (p less than 0.01) but less conspicuous parenchymal changes (focal necrosis, Kupffer cell proliferation, acidophil bodies, ballooning) than found in hepatitis type B (p less than 0.01). Steatosis occurred in 10% of the hepatitis A biopsies compared with 26% (p less 0.01) and 6% (not significant) in the hepatitis non-A, non-B and B groups, respectively. A comparison between the histological findings in women and men revealed that iron deposits occurred in more than half of the men compared to less than 20% of the women (p less than 0.01) irrespective of hepatitis type. Histological and biochemical follow-up was available in 36 patients with hepatitis A. For the majority of these patients the bilirubin concentration reached normal values within one month of the initial biopsy. The activity of serum transaminases showed good correlation with the degree of histological resolution. Non-specific reactive hepatitis with slightly raised serum transaminases were often seen during recovery from hepatitis A. These patients may be misinterpreted as cases of acute non-A, non-B hepatitis.

Adolescent↗

The long-term prognosis of non-transfusion-associated non-A, non-B hepatitis. A clinical, epidemiological, and histological investigation.

In a prospective study of the natural course of acute hepatitis, 157 of 1020 patients with biopsy-verified acute hepatitis could be classified as having hepatitis type non-A, non-B. We here report on the long-term prognosis for these 157 patients. The main type of exposure was drug addiction (40%), whereas 40% had no known hepatitis exposure. Only two patients had received blood products (blood transfusion and factor VIII). Follow-up liver biopsy (mean histological follow-up, 22 months) in 94 of the 157 patients showed chronic liver disease in 15-that is, cirrhosis in 6, suspicion of cirrhosis in 2, chronic aggressive hepatitis in 5, and chronic persistent hepatitis in 2. There was a striking predominance of elderly women with no known hepatitis exposure and with a high frequency of autoantibodies in serum among the patients with progression to chronicity, whereas chronic non-A, non-B hepatitis in drug addicts or after blood transfusions seems to be a limited problem. A comparison of histological features in the initial biopsies from patients with progression to chronicity or complete resolution showed piecemeal necrosis and abnormal bile duct epithelium to be of prognostic value.

Adolescent↗

Epidermal changes in heat and electrically injured pig skin. A light microscopic study of the influence of heat energy intensity and electrical current frequency.

Pigs were exposed to heat of low and high temperature and electricity of various frequences. Comparable amounts of energy were transferred in all experiments. In lesions induced by heat of low temperature granularity and/or fibrillarity of the cytoplasm were present in the epidermal cells. Lesions induced by heat of high temperature had a similar appearance, but occasionally "white necrosis", defects in the epithelium and light yellow material in stratum corneum were present. Lesions induced by 100.000 hz alternating current were segmental but otherwise microscopically often indistinguishable from lesions produced via transfer of heat of low temperature. Lesions induced by 8000 hz and 59 hz alternating current were segmental. Vesicular nuclei, "white necrosis" and yellow, clumped keratin were present in most lesions. Anode areas in direct current induced lesions showed a shrunken epidermis. The cytoplasm of the epidermal cells were often eosinophilic and homogeneous, and the nuclei were small with condensed chromatin. Occasionally, "empty" nuclei were noted. Yellow, clumped keratin was presented in all lesions. In cathode areas epidermis was of varying thickness and "white necrosis" and vesicular nuclei were present. The pathogenesis of the individual morphological features is discussed based upon theoretical concepts and the difference in morphology of the various lesions encountered in the present study as well as in other studies in this series of experiments. It is concluded that except for lesions produced via transfer of high frequency alternating current the morphology of electrical lesions is specific. Further, an alleged torture instrument was able to produce lesions similar to those observed in the experimental studies.

Animals↗

Light microscopic morphology of acute hepatitis non-A, non-B. A comparison with hepatitis type A and B.

Liver biopsies from a total of 240 patients with acute hepatitis A (86 patients), B (78 patients) and non-A, non-B (76 patients) were blindly evaluated for quantitative and qualitative light microscopic differences. No qualitative differences separate the three types of hepatitis, but the frequency and degree of some histological features seem to be characteristic of acute human non-A, non-B hepatitis. The degree of focal necrosis and portal inflammation was less pronounced in the non-A, non-B group as compared to the hepatitis A and B groups (P less than 0.01). Twenty-six percent of the non-A, non-B liver biopsies showed steatosis as compared with 10% and 6% in the hepatitis A and B groups, respectively (P less than 0.01). Bridging necrosis only occurred in liver biopsies from patients with non-A, non-B and B hepatitis. Abnormal bile ducts were detected in a total of five patients, three of whom were found in the non-A, non-B group. A comparison between histological findings in non-A, non-B patients with and without a possible intravenous exposure revealed that steatosis, cholestasis, large piecemeal necrosis and confluent necrosis occurred with the highest incidence in the patients without intravenous exposure, indicating that non-A, non-B hepatitis may be caused by more than one etiological agent.

Adolescent↗