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Biomedical subjects

J Saric

Publications and source records attributed to J Saric.

At least 73 records · Page 4Linked to original sources

[Hiatal hernia with intrathoracic gastric volvulus as a rare cause of biliary obstruction].

Gastric volvulus can complicate paraesophageal hiatal hernia. Acquired gastric torsion results in acute or chronic gastrointestinal symptoms. Biliary complications are possible but exceptional. A case of asymptomatic diaphragmatic hiatal hernia with intrathoracic gastric volvulus presenting as a cholestatic syndrome secondary to stretching and tension of the common bile duct in the diaphragmatic hiatus is reported. This observation emphasizes the possibility of direct relationship between two otherwise frequent diagnostics: hiatal hernia and biliary obstruction. Only one similar case has been reported to date.

Cholangiography↗

Changes in the alpha adrenergic system and increase in blood pressure with recombinant human erythropoietin (rHuEpo) therapy for renal anemia.

Recombinant human erythropoietin (rHuEpo) is effective in correcting renal anemia with the development of hypertension as the most frequent side-effect. Compared to hemodialysis patients with normal hemoglobin concentration, nine examined patients with transfusion-dependent renal anemia had low blood pressure in the context of high alpha 2-receptor densities and high plasma levels of catecholamines. This constellation can be explained by a defective receptor-ligand-interaction. During treatment with rHuEpo all patients showed an increase in blood pressure due to increased peripheral resistance, accompanied by a significant fall in plasma noradrenaline and alpha 2-receptor-density. There was a significant negative correlation between hemoglobin concentration and alpha 2-receptor density. We conclude that correction of renal anemia abolishes anemia-mediated disturbance of alpha 2-receptor function with the consequence of receptor down-regulation and increased vasoconstriction, which contributes to the rise in arterial blood pressure.

Adult↗

Characterization of liver-associated natural killer cells in patients with liver tumors.

The existence of a marginal lymphocyte population in rat liver sinusoids has already been demonstrated using the sinusoidal lavage method. We used the same technique to study the lymphocyte population in human liver obtained ex vivo after partial hepatectomy for benign or malignant tumors and compared it with peripheral and portal blood lymphocyte populations. Percentages of lymphocyte surface phenotypes were evaluated by flow cytometry. The lymphocyte population obtained from human liver is mainly made up of CD56+ (35%) cells. This percentage is three times greater than that found in peripheral and portal blood. Two-color flow cytometry analysis showed that within the CD56+ liver cell population, at least three distinct subsets could be found: (a) CD3+/CD56+/CD16-; (b) CD3-/CD56+/CD16-; and (c) CD3-/CD56+/CD16+. Although these subsets were also present in peripheral and portal blood, the percentage distribution was completely different because most CD56+ cells in peripheral and portal blood belonged to the CD3-/CD56+/CD16+ subset. These results show the existence of a heterogeneous natural killer cell population in human livers with tumors. The functional significance of this heterogeneity still needs to be explained.

Adult↗

Fine structure of hepatic sinusoids and sinusoidal cells in disease.

Liver sinusoids are special capillaries that are limited by fenestrated endothelial cells, without a genuine basement membrane, surrounded by perisinusoidal cells storing vitamin A, and harbouring Kupffer cells and pit cells, resident macrophages, and large granular lymphocytes, respectively. Each nonparenchymal cell and parenchymal cell of the liver interacts with all others and with the extracellular matrix. Therefore, the functional ability of each cell is constantly being modified by the metabolic activity of the others. Human liver biopsies (132), needle or surgical, perfusion-fixed with glutaraldehyde and processed for transmission electron microscopy (TEM), and occasionally for scanning electron microscopy (SEM), were examined. The study included liver diseases (such as alcoholic liver diseases, benign and malignant liver tumors, cholestasis of various origins, fulminant hepatitis, acute rejection after orthotopic liver transplantation, Budd-Chiari syndrome), as well as general or extrahepatic diseases (such as diabetes, hemochromatosis, hypervitaminosis A, various hematological disorders), and normal controls. Ultrastructural abnormalities are described and illustrated under two different headings: 1) elementary lesions of sinusoidal cells (endothelial, Kupffer, perisinusoidal and pit cells), nonsinusoidal cells (in the space of Disse and/or in the lumen), the extracellular matrix; and 2) the major pathological entities including perisinusoidal fibrosis, capillarization of sinusoids, sinusoidal dilatation, and peliosis. In the discussion, an overview of the major abnormalities reported in the literature is presented, and some specific questions regarding 1) perisinusoidal fibrosis in liver with normal histology, 2) the overload of perisinusoidal cells with lipids in non-hypervitaminosis A intoxication and 3) the etiological relationship of sinusoidal dilatation, peliosis, perisinusoidal fibrosis, or sinusoidal tumors with drugs and toxic compounds are discussed. In the event that lesions are not specific to any diagnosis, the knowledge of the ultrastructure of sinusoids is extremely useful from the perspective of the liver as an ecosystem.

Humans↗

Late recurrence of a hepatocellular carcinoma in a patient with incomplete Alagille syndrome.

In this study, the case of a patient presenting a second hepatocellular carcinoma 13 years after resection of a first tumor of the same type is reported. In this case, etiological investigations remained negative, but an incomplete form of syndromatic Alagille syndrome with paucity of bile ducts in the nontumoral tissue was detected and associated with nodular regenerative hyperplasia and foci of dysplasia. Malignant transformation in Alagille syndrome seems to be extremely rare. The fact that such tumors evolve very slowly could be an argument for partial hepatectomy and, if necessary, liver transplantation.

Bile Ducts↗

Nerves and perisinusoidal cells in human liver.

Unmyelinated nerve fibres are visible in the human hepatic lobule. They extend through the Disse space, surrounded by Schwann cell processes, often close to perisinusoidal cell processes. A few bare nerve endings or varicosities are found contiguous to either hepatocytes or perisinusoidal cells. These nerve endings or varicosities contain large and small granular vesicles and small clear vesicles. This heterogeneity probably corresponds to the presence of various neurotransmitters (noradrenaline, acetylcholine, various neuropeptides...). The effect of nerves on perisinusoidal cells has not yet been elucidated. However, the location, shape, morphology and origin of perisinusoidal cells would suggest that they play a role in the hemodynamic regulation of sinusoidal blood flow. It has recently been shown how important non-parenchymal-parenchymal communication is in the action of nerves on glucose release by hepatocytes; the cell to cell communications may also apply to nerves and sinusoidal cells for the hemodynamic regulation of sinusoidal blood flow.

Cell Communication↗

Chance discovery of hepatic fibrosis in patient with asymptomatic hypervitaminosis A.

A liver biopsy specimen was obtained from a 50-year-old patient whose clinical and functional liver tests showed no abnormalities but who had for some time a high vitamin A intake (109 X 10(6) IU over four years). Liver architecture was normal. Sinusoids were slightly dilated in zone 2. Perisinusoidal cells were numerous and enlarged. On Sirius red staining, there was mild fibrosis of the central veins, portal tracts, and terminal portal venules and perisinusoidal fibrosis in zone 1 of the acinus. Liver vitamin A level was increased. By electron microscopy, perisinusoidal cells filled with numerous lipid droplets had slightly dilated rough endoplasmic reticulum, numerous minute filament condensations below the plasma membrane, and stellate-shaped processes giving them the appearance of fibroblast-myofibroblast-like cells. Numerous collagen bundles, fibrils, amorphous material, and fragments of basement membrane-like material were identified in Disse's space. Immunocytochemistry showed increased amounts of collagen types I, III, IV, laminin, and fibronectin. This observation suggests that vitamin A per se, and not the cellular damage often seen in hypervitaminosis A, is responsible for fibrosis.

Biopsy↗

Removal of cellular debris formed in the Disse space in patients with cholestasis.

Using electron microscopy, we investigated how cellular debris, formed in the Disse space during cholestasis, was cleared. Ten patients with cholestasis of varied origin and severity were studied and compared with 10 controls without liver disease. In cholestatic patients, sinusoidal cells contained variable amounts of amylase PAS-positive material. In clean perfusion-fixed sinusoids the endothelial cells often appeared swollen and active, with few fenestrations. Hepatocyte blebs and cellular debris were sometimes seen in the Disse space. Two mechanisms were apparently involved in the clearing process: phagocytosis by macrophages either infiltrated into the Disse space, or forming the barrier; and the passage of debris from the Disse space into the sinusoidal lumen through the endothelial wall. Debris was either forced through enlarged pores or through the wall, with a progressive invagination followed by an outpouching in the lumen. The force, possibly provided by endothelial massage, may not be sufficient to push out cellular debris from the Disse space; morphological data seemed to indicate that endothelial damage may be a necessary factor. Debris present in the lumen was phagocytized by numerous active macrophages. Cellular debris was not observed in the Disse space of control patients.

Adult↗

Ultrastructure of sinusoidal cells in a benign liver cell adenoma.

A typical benign liver cell adenoma was removed from a 25-year-old female taking an oral contraceptive. The biopsy was perfusion-fixed, allowing good visualization of sinusoids and sinusoidal cells. Kupffer cells were seldom seen. Endothelial cells were of irregular thickness; most of them had few fenestrae and were attached to each other by well visible junctions. Normal perisinusoidal cells (PSC) were not seen but were replaced by myofibroblast-like cells with thick subendothelial processes. A basement membrane often underlaid endothelial cells and the processes of PSC. The enlarged Disse space with a flattened sinusoidal hepatocyte membrane contained occasional red blood cells and an abundant extracellular matrix but few collagen fibers. These sinusoidal abnormalities leading to the capillarization of sinusoids, either the cause or the consequence of the disease, indicated a loss of normal hepatocyte homeostasis.

Adenoma↗

Sinusoids ultrastructure of human hepatocellular carcinoma.

Sinusoids ultrastructure was studied in a case of hepatocellular carcinoma developed in the non cirrhotic liver of a 40-year-old man. The surgical biopsy was perfusion-fixed with 1.5% glutaraldehyde. The number of Kupffer cells was very low. Endothelial cells with signs of hyperactivity were very irregular; digitations were often attached by numerous well identified junctional complexes to their own cell processes or to adjacent cell processes. Perisinusoidal cells without lipids resembled fibro-myofibroblasts. Discontinuous basement membranes underlaid endothelial cells and perisinusoidal cells. In addition numerous strands of short basement membranes segments were seen in the Disse space. Well organized bundles of collagen were not seen. The sinusoidal membranes of hepatocytes were flattened. The perfusion-fixation revealed to be a very useful technique in the identification of all these changes which have also been reported to some degree in benign liver cell adenoma and in cirrhosis; these two conditions are known to be associated with hepatocellular carcinoma.

Adult↗

[Easily closed gun-barrel enterostomy. A new technique].

The availability of continuous low rate enteral and parenteral feeding has enlarged the indications of enterostomy, notably in patients with multiple operations. However, closing an enterostomy, which may be high up in the small bowel, rises technical problems and is not always without risk. In this study a new technique of gun-barrel enterostomy easily closed with automatic sutures and without reopening of the abdominal wall is presented.

Humans↗

Hepatocyte ultrastructure in rats with portacaval shunt. A morphometric study of acinar zones.

The principal reported morphological consequence of portacaval shunt in the rat is liver atrophy. The present study was designed to investigate ultrastructural changes in hepatocytes using electron microscopy morphometry. Two weeks following portacaval shunt, rat livers were fixed by perfusion and hepatocyte organelles from the two opposite zones of the acinus (zones 1 and 3) were quantified. Liver weight/body weight decreased by 50%, hepatocyte-specific volume decreased by 30% (28% in zone 1 nd 35% in zone 3). Estimated sinusoidal space increased, and estimated number of hepatocytes decreased by 50%. Hepatocytes had a normal ultrastructure except for mitochondria. Smooth endoplasmic reticulum-specific surface area was reduced by 65% (zone 3), and rough endoplasmic reticulum surface density was increased in zone 1 only. Mitochondria-specific volume was unchanged but decreased inner and outer membrane-specific surface area in zone 3 suggests in this zone a change in their conformation and possibly their number. Golgi-rich area surface density increased but not significantly. Hepatocyte loss and atrophy and rearrangement of organelles represent a new ultrastructural steady state following portacaval shunt that may help explain the new functional steady state.

Animals↗

Early patchy hepatic necrosis. Its appearance after bile-duct ligation in rats with a portacaval shunt.

We incidentally observed that rats with portacaval shunts (PCS) had patchy hepatic necrosis after bile-duct ligation (BDL). Rats with two weeks of PCS underwent BDL, then were killed after 0,5 or 20 hours, or two or four days; rats undergoing sham PCS were used as controls. Patchy hepatic necrosis distributed at random within the acinus was mainly lytic after five and 20 hours, then displayed inflammatory features after two days. The inflammation tends to disappear by four days, with a differentiation of new hepatocytes into neo-bile ducts. These necrotic areas were 60 times more severe after five hours, and 20 times more severe after 20 hours in rats undergoing PCS than in those undergoing sham PCS. In the former group, necrosis after five hours represented 1.92% of the total area examined. Histological characteristics and the high incidence with PCA suggest that necroses have vascular origin.

Animals↗

Liver arterialization improves hepatocytes ultrastructure in rats with portacaval shunts.

The effect of arterialization (ART) of the distal stump of the portal vein after portacaval shunt (PCS) on bile formation and liver ultrastructure was assessed. ART using the left gastric artery was performed in male Wistar rats. Animals were sacrificed 3 weeks later. ART prevented body and liver atrophy. However, the liver weight to body weight ratio was significantly decreased when compared to sham PCS (2.5 +/- 0.36 vs 3.22 +/- 0.15). Reduction in total bile secretion (microliter/min) seen following PCS is reversed by ART. ART partly corrected hepatocyte size atrophy and the major ultrastructural abnormalities, namely the irregularity of the nucleus and dilation of the nuclear envelope and of the rough endoplasmic reticulum appearing after PCS. However, mitochondria remained swollen, deformed and enlarged with scission figures. No lesions in connection with ART were seen. This result confirms, at the ultrastructural level, the beneficial effect of ART in PCS.

Animals↗

Chronic biliary drainage corrects liver atrophy induced by portacaval shunt in the rat.

Portacaval shunt induces a severe liver atrophy. The relative liver hypertrophy induced by chronic biliary drainage was studied by electron microscopy. Rats with either portacaval or sham portacaval shunt had a 4-day chronic bile fistula. Compared with rats not submitted to chronic bile fistula, liver weight/body weight ratio increased from 1.84 to +/- 0.12 to 3.54 +/- 0.48 (p less than 0.05) in portacaval shunt and from 3.52 +/- 0.15 to 3.64 +/- 0.40 (p less than 0.05) in sham portacaval shunt (controls). Chronic bile fistula stimulated bile acid synthesis in the two groups. Furthermore, the initial low bile flow observed in portacaval shunt (rats) reached control values after chronic bile fistula. Ultrastructural abnormalities observed in portacaval shunt: atrophy of the hepatocyte mainly related to the atrophy of the rough and smooth endoplasmic reticulum, irregularity of the nucleus, dilatation of the nuclear envelope and of the rough endoplasmic reticulum, and swelling of mitochondria, were greatly modified by chronic bile fistula. The hepatocyte size increased, mitochondria appeared smaller than normal, the nuclear envelope and the rough endoplasmic reticulum were not dilated, and the rough and smooth endoplasmic reticulum were expanded. Chronic bile fistula had no noticeable effect on the liver in sham portacaval shunt. Either stimulation of bile salts synthesis or removal of bile salts, which could be toxic for the atrophic liver, are possible explanations for the relative hypertrophy of the liver.

Animals↗