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Biomedical subjects

B Jeppsson

Publications and source records attributed to B Jeppsson.

At least 109 records · Page 6Linked to original sources

Retarding liver cancer growth in the rat by transient repeated hepatic dearterialization.

The effect of repeated ischemic episodes to experimental liver tumors is studied in a group of inbred Wistar-Furth rats. A vascular occluder model was developed specially for the purpose of delivering intermittent compressions to the hepatic artery in the rat. With five daily 1-hr occlusions of the hepatic artery, rats benefited from significantly reduced tumor growth rates compared with controls that underwent sham operation (P less than 0.05). In contrast to results from previous pig experiments, it is demonstrated by angiographic studies that repeated transient dearterialization does not entirely overcome the problem of collateral vessel formation in the rat. Tumor neovascularization continues irrespective of whether the tumor is being dearterialized. It is also observed that in both normal and tumor rats, collateral channels from the left gastric artery temporarily open up when the hepatic artery is obstructed but disappear on reestablishment of flow. As such types of collateral flow are beyond our control, it is imperative that future developments in vascular occlusion therapy should aim at shortening ischemia time and combining with chemotherapy.

Adenocarcinoma↗

Organ sequestration of 65Zn during experimental sepsis.

Alteration in the metabolism of zinc during infections has been reported. We have studied the redistribution of endogenous zinc by making the animals physiologically stable by daily intra-gastric administration of 65Zn prior to the induction of sepsis. Organ uptake of exogenous zinc was studied by investigating the organ uptake of 65Zn after an intravenous injection during sepsis. Male Sprague-Dawley rats, were kept in metabolic cages to monitor the excretion of the radioisotope. They were made septic using a gelatine capsule containing E. coli, Bacteroides fragilis in a standardised mixture with sterile rat faeces and barium sulphate, implanted into the abdomen. The plasma radioactivity in the septic state was significantly lower when compared to control rats. In the septic state, there was an increased uptake of endogenous zinc after oral administration of radioactive zinc in the liver, pancreas, large intestine and testes. When administered intravenously in septic animals we found a decreased uptake of exogenous zinc in the pancreas, large intestine, small intestine, bone and testes. Thus the distribution of endogenous and exogenous zinc seems to differ during the septic state.

Journal Article↗

Status of ischemic therapy for hepatic tumors.

The use of hepatic artery ligation or permanent dearterialization as the sole procedure for the palliation of patients with malignant hepatic tumors has no proved value. The combination with cytotoxic drug administration via the portal route may offer some advantage. The use of transient dearterialization with one longer ischemic period has been successful in the treatment of metastatic carcinoid disease with carcinoid syndrome but ineffective in the treatment of other hepatic tumors. New knowledge of the effects of transient ischemia on the formation of arterial collaterals and the pathophysiologic mechanisms in cellular injury has led us to further refinement of this therapeutic principle. The first results of repeated short periods of ischemia are promising and give some hope for the future palliation of this group of tumor patients.

Combined Modality Therapy↗

Diagnostic cholangioscopy--comparison with conventional methods (radiology, ultrasonography).

The goals of surgery for calculous biliary disease are to explore as few normal bile ducts as possible and to remove all calculi. The most commonly used techniques to help eliminate residual stones are: exploration of all or most common ducts; operative cholangiography; intraoperative ultrasonography or choledochoscopy. Exploration of common bile ducts on clinical diagnoses leads to high number of negative explorations and has been abandoned. Operative cholangiography performed with modern technique with the use of fluoroscopy is very accurate with a diagnostic accuracy of well above 95%. Cholangiography can be performed preoperatively with the same diagnostic accuracy and thereby save operative time. Intraoperative ultrasonography has recently been introduced for the diagnosis of residual stones and seems to be superior to cholangiography. It is of limited use however, for intrahepatic stones. Intraoperative choledochoscopy finally is the most superior way of achieving intraoperative diagnosis of common bile duct stones. With the advances of ERC and other non-operative techniques, the consequences of leaving calculi in the bile duct are less severe today than before. Non-operative retrieval by percutaneous, endoscopic means or chemical dissolution are effective ways of dealing with residual stones.

Bile Duct Diseases↗

Superoxide production of peritoneal macrophages in experimental gram-negative sepsis; influence of in vitro and in vivo supplements of zinc.

Although zinc is essential for the optimum function of the immune system, there is some controversy regarding treatment with zinc during acute infections where low serum zinc levels are often recorded. The aim of the present study was to investigate the influence of in vitro and in vivo zinc supplementation on the potentially toxic metabolic activity of peritoneal macrophages during infection. Rats were made septic by implanting a gelatin capsule containing known amounts of E. coli, and Bacteroides fragilis into the abdomen. Peritoneal macrophages were harvested by peritoneal lavage 72 hours after the induction of sepsis. Superoxide release was measured after stimulation with phorbol myristate acetate (PMA) or serum treated zymosan (STZ). Macrophages from septic rats released significantly higher amounts of superoxide compared with macrophages from sham operated controls after stimulation with both PMA and STZ. Following in vitro supplementation, zinc inhibited the superoxide production of macrophages harvested from septic rats after stimulation with both PMA and STZ. In vivo supplementation with zinc resulted in increased superoxide production from septic macrophages when stimulated with STZ, whereas stimulation with PMA produced no significant changes. Thus, in vitro incubation inhibited the superoxide production of peritoneal macrophages in intraabdominal sepsis, whilst in vivo administration of zinc produced no such effect, and the effect seemed to vary depending on the stimuli used to initiate the respiratory burst.

Animals↗

Acute ischemic liver failure in the rat: a reproducible model not requiring portal decompression.

We report a model of acute ischemic liver failure which does not require temporary or permanent portal decompression. The model is induced by segmental ischemia of the median and left lateral lobes for 100 min by a vascular clamp applied on the afferent vessels. Declamping is followed by resection of the nonischemic right lateral and caudate lobes. No portal stasis occurs as blood flow to the right lateral and caudate lobes is maintained during the period of clamping. The 24-hour mortality is 76.5%. Evidence of severe liver damage is shown by histological and biochemical studies.

Acute Disease↗

Thioacetamide- and carbon tetrachloride-induced liver cirrhosis.

Two methods of inducing liver cirrhosis in the rat were studied. Intragastric administration of CCl4 for 16 weeks according to Proctor and Chatamra was compared to the administration of thioacetamide in the drinking water (0.3 g/l) for the same period. CCl4 administration induced micronodular cirrhosis in 6/8 animals with a 27% mortality. Thioacetamide induced cirrhosis in 6/8 animals without mortality. The histologic pictures differed somewhat in that the CCl4 group exhibited more necrosis and cellular swelling while the thioacetamide group had more nuclear atypias and proliferation. Biochemically both groups had elevated plasma levels of aspartate aminotransferase. The lysosomal enzyme beta-hexosaminidase (beta-NAG) showed a transient increase in the thioacetamide animals, while beta-glucuronidase decreased. CCl4-induced cirrhosis led to an increase in beta-NAG. Plasma zinc decreased in both groups as well as liver zinc content in the CCl4 group, while there was a continuous elevation of liver zinc in the thioacetamide group. We conclude that oral administration of thioacetamide is a simple and reliable method of inducing experimental liver cirrhosis. The differences in histological appearances and some biochemical parameters may be caused by the different mechanisms of action of thioacetamide and CCl4.

Acetamides↗

Enteral versus parenteral glucose as the sole nutritional support after colorectal resection. A prospective, randomized comparison.

Twenty consecutive patients undergoing resection for colorectal carcinoma were randomized to receive either a glucose polymer by nasojejunal tube or glucose by intravenous infusion as the sole postoperative nutritional support for 4 days. Identical amounts of glucose were given by the two routes. Brief infusions of insulin (10 mU kg-1) and glucose (25 g) were given before and 4 days after surgery for the purpose of metabolic evaluation. Blood glucose was consistently lower in the enteral than in the parenteral group (p less than 0.05). Glucose tolerance and the hypoglycemic response to insulin were impaired after surgery in the parenteral group (p less than 0.01 in both cases) but not in the enteral group. Clearance and release of insulin were similar before and after surgery and were similar in both groups. Patients receiving enteral glucose had less postoperative distress and required fewer doses of analgesic drug (p less than 0.05 in both cases). It is concluded that enteral infusion of glucose preserves insulin action and glucose tolerance after colorectal resection, whereas intravenous infusion of glucose does not. The favorable metabolic effects seen after enteral infusion are accompanied by a reduction of postoperative discomfort.

Adult↗

Biliary tract cancer--treatment options.

Cancers of the extrahepatic biliary tract are rare, but they pose great problems from diagnostic and therapeutic points of view. Surgical resection offers the only prospect of cure for patients with this type of cancer. The resectability rates vary from 50% for tumours in the lower common bile duct to only 10% for tumours in the upper third. For the first group of patients there is a 5-year survival rate of 20-30% in several reports and for the other 10-15%. The operative mortality is acceptable low. For tumours in the liver hilum a liver resection is recommended. Most patients can only be helped by a by-pass procedure. The operative by-pass procedure carries a significant morbidity and mortality and most patients should be drained by PTC or preferably endoscopically. The effects of radiotherapy and chemotherapy have so far been insignificant. The combined use of intraarterial chemotherapy combined with radiotherapy seems to offer some advantage and this treatment modality must undergo further trials.

Biliary Tract Neoplasms↗

Tumour calcification following repeated hepatic de-arterialization in patients: a preliminary communication.

A novel method of repeated hepatic de-arterialization is presented. A vascular occluder is placed around the hepatic artery and connected to an injection port. The hepatic artery can thereafter be occluded repeatedly. Patients with irresectable liver metastases from colorectal cancers were treated with occlusions of the hepatic artery for 1 h twice daily, in combination with intraperitoneal cyclic administration of 5-fluorouracil. The first three patients treated are presented. They all exhibited massive tumour calcifications in the liver reflecting tumour necrosis and resorption. This therapeutic principle must undergo further clinical trials.

Adult↗

Intraperitoneal infusion of 5-FU in liver metastases from colorectal cancer.

Intraperitoneal 5-fluorouracil (5-FU) was given to eight patients with unresectable colorectal liver cancer and to one patient after radical hepatectomy. A subcutaneous intraperitoneal access device was implanted, and treatment consisted of continuous infusion of 1,000 mg 5-FU/d for 5 days, repeated every 6 weeks. Evaluation of treatment was performed after every two cycles of therapy. A total of 32 infusion cycles were given. The mean steady-state concentration of 5-FU was 0.56 +/- 0.04 mumol/l (mean +/- SEM), and the total body clearance was 10.0 +/- 0.71/min mean +/- SEM). The levels of 5-FU in peripheral venous blood were stable and reproducible. When incubated in whole blood at 37 degrees C the concentration of 5-FU fell rapidly and after 2 h, only 22% of the starting level remained. When kept ice-cold, 5-FU samples were stable. Patient acceptance was excellent, and the therapy was free from complications except for slight abdominal discomfort, not enough to require alleviation by analgesic drugs. Computerized tomography (CT) scan showed stationary tumor volume after two cycles of therapy in four of eight patients who could be evaluated. It is concluded that continuous intraperitoneal infusion of 5-FU produces stable and reproducible levels of the drug in peripheral venous blood, that 5-FU is degraded by blood cells at 37 degrees C, that the use of a subcutaneous access device makes the delivery easy and safe, and that the efficacy of the therapy seems to be similar to that obtained with hepatic arterial infusion.

Abdomen↗

Combined intermittent dearterialization and intraperitoneal 5-fluorouracil administration for liver tumours in the rat.

Arterial occlusive therapy in the palliation of liver cancers has gone a long way since the first attempt at hepatic artery ligation. While efforts in permanent hepatic dearterialization have been frustrating in the face of fast developing collaterals, temporary inhibition of hepatic arterial blood flow appears to offer definite advantages. The effect of a single transient hepatic arterial occlusion with and without the addition of intraperitoneal 5FU was tested in Wistar-Furth rats bearing liver tumours. No advantage was observed in terms of tumour growth inhibition unless toxic doses of 5FU were used. A 5-day course of repeated treatment using intermittent dearterialization combined with intraperitoneal 5FU infusion was next tested and was found to be an efficient approach in reducing tumour growth rates. We prefer the intraperitoneal rather than the intraportal route for the infusion of oncolytic drugs because it avoids the problem of portal thrombosis and at the same time deals with any concomitant extrahepatic disease.

Animals↗

Influence of 2-deoxy-D-glucose and arterial ischaemia on glucose oxidation and growth of liver cancer in the rat.

Malignant tissues are known to exhibit a high rate of glucose oxidation. It could therefore be hypothesized that reduction of glucose oxidation could be of benefit for the treatment of malignancies. We tested this approach, and by using [UL14C]glucose, we showed that glucose oxidation in a transplanted adenocarcinoma in the rat liver was 2.81 +/- 0.23 times as high as that of the surrounding liver tissue (P less than 0.01). In vivo treatment with intra-arterial 2-deoxy-D-glucose (2DG) infusion at 800 mg/kg via the gastroduodenal artery reduced the tumour/liver ratio of glucose oxidation to 1.88 +/- 0.12 (P less than 0.01). A similar inhibition of tumour glucose oxidation was obtained by 1 h of hepatic arterial ischaemia (P less than 0.05), or by ischaemia combined with 2DG infusion at 400 mg/kg (P less than 0.01). A 5-day course of intermittent hepatic dearterialization combined with continuous intra-arterial 2DG infusion at 400 mg/kg/day produced liver tumour growth retardation (P less than 0.01). We conclude that intermittent dearterialization reduces not only tumour growth but also the high tumour glucose oxidation. Dearterialization reduced glucose oxidation as much as 2DG did, which could be a mechanism behind reduced tumour growth.

Adenocarcinoma↗

Trace element alterations in infectious diseases.

Trace elements like copper, zinc, iron and selenium have a significant influence on the function of the immune system. We studied plasma levels of trace elements in 53 patients with acute bacterial and viral infections. In bacterial infections (septicaemia, pneumonia, erysipelas and meningitis) the plasma concentrations of selenium, iron and zinc were decreased. Plasma copper was unchanged in patients with erysipelas, but increased in other types of bacterial infections. Although the patients with viral infections showed similar shifts of the trace elements as were observed in patients with bacterial infections, the changes were not as pronounced. A plasma selenium value below 0.8 mumol/l was found in only 6% of the patients with viral infections in contrast to 63% of the patients with septicaemia or 57% of the patients with pneumonia. Furthermore, in viral infections 60% of the zinc values were below the mean level of 12.8 mumol/l observed in healthy controls as compared with 90% of the values in patients with sepsis or 92% of the values in patients with pneumonia. The onset of change in trace elements occurred within a few days and persisted for several weeks. These changes seem to be non-specific and are independent of the agent causing infection. The different types of infections were followed by changes in most of the plasma proteins which are known to be associated with an inflammatory reaction. The changes in plasma proteins were most pronounced in patients with sepsis and pneumonia. Patients with sepsis having a high degree of inflammation did not show a positive correlation between the severity of the disease--as judged by plasma proteins--and the alterations of trace elements.

Bacterial Infections↗