[Experiments in surgery at Landskrona hospital].
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Emergency Service, Hospital↗
Biomedical subjects
B Jeppsson
Publications and source records attributed to B Jeppsson.
[Medical information for administrators].
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Education, Medical↗
Repeated hepatic ischemia as a treatment for carcinoid liver metastases.
Hepatic ischemia has been used in the treatment of bilobar malignant carcinoid tumors in the liver. Hepatic artery ligation, hepatic dearterialization, and embolization with nondegradable micromaterial have been followed by collateral formation and are associated with a high complication rate. To reduce this, an implantable vascular occluder permitting intermittent occlusion of the hepatic artery was used in 3 patients with bilateral malignant carcinoid in the liver, with high urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA). Following a thorough dearterialization of the liver and division of all attachments, except for the hepatic artery, portal vein, and common duct, the vascular occluder was placed around the hepatic artery and connected to an implantable subcutaneous port. The hepatic artery was occluded by injecting a few milliliters of saline into the port and flow was released by withdrawal of the same amount of saline. Two patients had an anomalous blood supply to the right lobe and the arterial branch was transposed to the proper hepatic artery. One patient had the hepatic artery regularly occluded for 16 hours at 4-6 week intervals. Two patients managed to do the occlusions by themselves at home for 1 hour twice daily. Two patients had a normalization of the urinary excretion of 5-HIAA after 4 and 9 months. On follow-up with computed tomographic scanning, tumor regression was noted in one, however, there was no change in the other. The third patient has already had a 75% reduction of urinary excretion of 5-HIAA after 2 months of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Carcinoid Tumor↗
Oral arginine supplementation in acute liver injury.
Acute liver failure is accompanied by a high rate of bacterial and septic complications. Arginine has a potent effect on the immune system and modulates bacterial clearance in septic models. We studied the effect of oral arginine supplementation on the extent of liver injury and the associated bacterial translocation in an acute liver injury model in rats. Sprague-Dawley rats were divided into normal, liver injury, and arginine supplemented groups. In the arginine group, 2% arginine was supplemented daily through a nasogastric tube for 8 d. Acute liver injury was induced on the eighth day by intraperitoneal injection of D-galactosamine (1.1 g/kg body wt). Samples were collected 24 h after the liver injury. In the arginine-supplemented group, alkaline phosphatase, bilirubin, and aspartate aminotransferase were reduced significantly compared with the acute liver injury control group. The results of bacterial translocation in the arginine-supplemented group showed a significantly reduced number of translocated bacteria to the liver and mesenteric lymph nodes than occurred in the acute liver injury group. The histological study of the liver in arginine-supplemented group showed scattered areas of hepatocellular necrosis and inflammatory cell infiltration, and in the acute liver injury group there were more and widespread hepatocellular necrosis and inflammatory cell infiltration. Oral supplementation of arginine in an acute liver injury model improves significantly the state of the liver injury and reduces bacterial translocation to the liver and mesenteric lymph nodes.
Acute Disease↗
Identification of the translocating bacteria in rats with acute liver injury and their relation to the bacterial flora of the intestinal mucosa.
The bacterial flora of the intestine and the bacteria found in liver, mesenteric lymph nodes, portal and arterial blood after D-galactosamine-induced liver injury, with and without pretreatment with Lactobacillus plantarum DSM 9843, were studied in the rat. Dominating representatives were identified to species level by 16S rDNA sequencing and typed by randomly amplified polymorphic DNA (RAPD) and by restriction endonuclease analysis (REA) for strain definition. It was proven that bacterial strains from the intestine occur at extraintestinal sites after liver injury. Lactobacillus spp. dominated the intestinal flora and were also the most frequently found genus in the liver and the mesenteric lymph nodes. Some of the blood isolates, identified as Staphylococcus aureus, Proteus vulgaris and Bacteroides merdae, were not found as a dominating part of the mucosal flora. Treatment with L. plantarum before liver injury decreased translocation and made the intestinal flora increasingly dominated by lactobacilli.
Acute Disease↗
Isolated liver perfusion permits administration of high doses of chemotherapeutic agents. Comparison with hepatic artery infusion.
Tumor cells are dependent on glutamine metabolism and acivicin, which is a selective glutamine antagonist, has been shown to effectively retard tumor growth in several malignancies. However, systemic treatment with acivicin is associated with significant side effects. The purpose of the present study was to examine whether use of an in vivo isolated liver perfusion model may allow administration of lethal doses of acivicin and compare it to regional infusion of acivicin in the hepatic artery. Five days after tumor inoculation, acivicin was administered by an isolated liver perfusion model or by regional infusion via the hepatic artery. It was found that regional infusion of acivicin (5 and 10 mg/kg) via the hepatic artery caused systemic illness and diarrhea, and all animals in this group died within 3 days. In contrast, we observed no signs of systemic illness, diarrhea or hepatocellular injury in rats receiving isolated liver perfusion with or without acivicin (10 mg/kg) administration. Noteworthy, we found that isolated perfusion with acivicin reduced the glutamine content in liver tumors by 39% compared to perfusion with control medium. In line with this, it was found that isolated perfusion with acivicin (10 mg/kg) inhibited tumor growth in the liver. Taken together, this study suggests that application of the isolated liver perfusion model avoids the toxic and lethal effects of high doses of chemotherapy, herein acivicin, and may provide a useful approach to treat liver tumors in vivo.
Adenocarcinoma↗
Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor on intra-abdominal adhesions.
BACKGROUND: Formation of intra-abdominal adhesions depends, in part, on the activity of serine proteinases. Matrix metalloproteinases (MMP) are required for epithelialization of skin wounds but their involvement in mesothelialization of peritoneal wounds and in adhesion pathogenesis is not known. Early tumor necrosis factor-alpha (TNF-alpha) levels have been proposed to reflect propensity to adhesion formation. OBJECTIVE: The impact of MMP activity and secreted TNF-alpha on peritoneal adhesion formation and healing was investigated through systemic administration of the synthetic broad-spectrum MMP and TNF-alpha-converting enzyme (TACE) inhibitor GM 6001. METHODS: Female Sprague-Dawley rats of 4-6 weeks of age were injected subcutaneously daily with GM 6001 100 mg/kg (n = 12) or vehicle (n = 10) starting two days before surgery. In each rat, two standardized peritoneal wounds, 20 mm x 5 mm, were made. One peritoneal wound was sutured whereas the contralateral wound healed by secondary intention. Adhesion formation and peritoneal healing, cell proliferation, and hydroxyproline concentrations were evaluated on postoperative day 7. RESULTS: Total serum TNF-alpha levels increased in vehicle-treated rats (p = 0.019) while GM 6001 treatment effectively prevented the rise in the postoperative phase (p < 0.001). No significant differences were observed in the extent of adhesion formation (p = 0.67) between control (65.0%) and GM 6001-treated (61.5%) animals, or peritoneal wound healing or cell proliferation. Hydroxyproline levels increased in the wounds (p = 0.014) but were not different between the two groups (p = 0.14). CONCLUSIONS: Lack of a striking effect of the MMP and TACE antagonist GM 6001 on postoperative adhesions suggests that MMP activity and TNF-alpha might not be major adhesiogenic factors.
ADAM Proteins↗
Amino acids and indoleamines in the brain after infusion of branched-chain amino acids to rats with liver ischemia.
Rats with a portacaval anastomosis and ligation of the hepatic artery 2 days later were infused for 6 hr with a 10% glucose solution (group I) or the same solution combined with 0.24 M/liter branched-chain amino acids (BCAA, group II). Control animals with portacaval anastomosis and sham-operation (group III) or two sham-operations (group IV) were infused with a 10% glucose solution. The rats were killed by decapitation and indoleamines and amino acids were determined in the brain. Rats with liver ischemia were stuporous at the end of the experiment irrespective of treatment. The concentrations in the cortex of lysine, methionine, phenylalanine, threonine, alanine, glutamine, glycine, histidine, and tyrosine were significantly increased in group I compared to group IV. Infusion of BCAA to rats with liver-ischemia (group II) resulted in significantly lower concentrations of lysine, methionine, phenylalanine, threonine, histidine and tyrosine and increased concentrations of isoleucine, leucine, valine, and arginine compared to group I. The content of serotonin in the cortex and brain stem was significantly increased in group I compared with the BCAA-treated animals (group II) and the control groups III and IV. The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the cortex and brain stem were higher in group I than in group IV. Infusion of BCAA to rats with liver ischemia normalized the concentrations of 5-HIAA in the cortex and brain stem.
Amino Acids↗
Serotonin metabolism in the central nervous system in portacaval shunted rats infused with fat emulsion.
Increased brain concentrations of tryptophan, and presumably thereby increased brain serotonin metabolism, have been observed following liver impairment and implicated in the etiology of portal-systemic encephalopathy (PSE). Increased plasma-free tryptophan (ie, not albumin-bound) concentrations can be expected after exogenous fat administration. This might further increase the brain serotonin metabolism in liver failure and negatively influence the PSE. We treated rats 2 weeks after end-to-side portacaval shunt (PCS) with continuous intravenous infusion of fat emulsion (Intralipid 20%) for 24 and 72 hr, respectively. The regional serotonin turnover was determined in different regions of the central nervous system (CNS) by measuring 5-hydroxyindole concentrations after NSD 1015 decarboxylase inhibition. The results revealed no further increase of the CNS serotonin turnover after fat infusion to PCS rats, compared with PCS rats given equal amounts of glucose. Thus, continuous infusion of a fat emulsion caused no major alteration of the CNS serotonin metabolism in PCS rats.
Animals↗
Serotonin receptors in the brain following total hepatectomy in rats treated with branched-chain amino acids.
Serotonin concentrations and receptor binding characteristics were investigated in rats subjected to total hepatectomy, portacaval shunt (PCS) or sham-operation. The animals were infused for 5 hr with a 10% glucose solution or the same solution enriched with 0.24 M branched-chain amino acids (BCAA). Hepatectomized animals were in grade-two coma at the end of the experiment independent of infusion. Indoleamines in mesencephalon-pons and diencephalon were analyzed by high-pressure liquid chromatography with electrochemical detection. Serotonin receptors (5-HT1 and 5-HT2) were investigated in the cortex and hippocampus by radioligand binding studies using 3H-serotonin for analysis of 5-HT1-receptors and 3H-ketanserin for analysis of 5-HT2-receptors. Concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were significantly increased after hepatectomy compared with controls. Treatment with BCAA significantly decreased 5-HT and 5-HIAA levels in hepatectomized animals. The affinity and the number of binding sites for the 5-HT1 and 5-HT2 receptors were found to be similar in all groups. The present study indicates that PCS for 1 week and the anhepatic state for 5 hr in rats do not influence brain serotonin receptors in contrast to previous studies in pigs with liver ischemia or rabbits with galactosamine-induced liver damage. In addition, infusion of BCAA for 5 hr did not alter the binding characteristics.
Amino Acids, Branched-Chain↗
Gastrointestinal surface protection and mucosa reconditioning.
BACKGROUND: There is increasing evidence that preservation of the ecology of the gastrointestinal tract and the surface protection system--surfactants, mucus, and fiber--is important for the outcome in postoperative trauma patients, patients after bone marrow and liver transplantation, and patients with HIV or AIDS. Approximately 50% of the nourishment of the small intestine and > 80% of the nourishment of the large intestine comes from the lumen. This is especially deleterious to the large intestine. Within less than a week of intestinal starvation--even in the presence of intense parenteral nutrition--a mucosal atrophy is observed, promoting translocation of potentially pathogenic microorganisms. Enteral nutrition is crucial to the outcome in many of these conditions. If however, such a nutrition is based on simple carbohydrates, peptides, amino acids, or fatty acids, most of the nutrition administered will be absorbed in the upper gastrointestinal tract. Complex fibers and proteins can be regarded as nutrients especially destined to the lower gastrointestinal tract. They are fermented by the probiotic flora, normally colonizing the colonic mucosa, and the necessary nutrients: short-chain fatty acids and amino acids such as arginine and glutamine are produced at the level of the colonic mucosa. Careless antibiotic treatment reduces or eliminates this flora, induces local mucosal starvation, and makes the patients vulnerable to opportunistic infections and microbial intestinal translocation. METHODS AND RESULTS: In this review the role of the different ingredients of the surface protection system are discussed. A program to recondition the intestines, particularly the colonic mucosa by resupply of species-specific lactobacilli, surfactants, amino acids (especially glutamine), and oat fiber (beta-glucans) is suggested. Extensive experience in animal models and early experience in a patient population are summarized and discussed. Oat has been chosen as a substrate for fermentation because it contains 100 times more of membrane lipids (surfactants) than any other food, has a favorable amino acid pattern (rich in glutamine), and is rich in water-soluble, fermentable-fiber beta-glucans. More than 1000 isolates of human-specific lactobacilli have been studied. Some strains, especially those of plantarum type, have proven effective in colonizing the colonic mucosa, suppressing the potentially pathogenetic flora, and may have other probiotic effects as well. CONCLUSION: A totally new enteral formula has been designed based on probiotic bacteria and fiber and aimed at colonizing the intestinal mucosa with a local probiotic effect and fermentation of fiber.
Animals↗
The effect of pancreatic and intestinal venous blood on hepatic atrophy and compensatory hyperplasia in the rat.
Hepatotrophic effect of pancreatic and intestinal venous blood was studied in rats with mesocaval or distal splenocaval shunt following ligation of a branch of the portal vein supplying 70% of liver mass. Because 2/3 of liver mass was deprived of portal flow the nonligated liver lobes were not hypoperfused due to shunt procedure. During the first three postoperative days the DNA synthesis, mitotic index, and changes in relative weights were measured in both ligated (atrophied) and nonligated (compensatory hyperplasia) parts of the liver. It was found, that the restorative capacity of the liver existed in rats with selective portasystemic shunts. The stimulus to growth was greater in lobes supplied by intestinal venous blood compared to those perfused by pancreatic effluent. The increase in DNA synthesis occurred in lobes undergoing atrophy and the intensity of this response was also dependent on type of shunt since recirculation of intestinal blood by way of the hepatic artery inhibited atrophy to a greater extent than pancreatic venous effluent. Although the patency of arterial branches was confirmed the ligated lobes showed necrotic lesions. Systemic recirculation of intestinal venous blood far more inhibited necrosis than pancreatic venous blood.
Animals↗