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Biomedical subjects

S Bengmark

Publications and source records attributed to S Bengmark.

At least 163 records · Page 9Linked to original sources

Factors influencing the outcome of E. coli peritonitis in rats.

Substances that may influence the course and outcome of intra-abdominal sepsis were investigated in an experimental model of Escherichia coli peritonitis in rats. All rats received an intraperitoneal injection of E. coli. In the first set of experiments, substances commonly contaminating the abdominal cavity after trauma were intraperitoneally injected, and the following mortality rates were found: saline solution (controls) 27%, hemoglobin solution 80% (p less than 0.01), whole blood 20% (p greater than 0.05), whole blood together with bile 93% (p less than 0.001) and bile 87% (p less than 0.01). In the second set of experiments, intravenous injection of commonly used solutions gave mortality rates of 20% (controls) for saline solution, 80% for dextran (p less than 0.01) and 47% for Intralipid (p greater than 0.05). E. coli peritonitis in rats thus was aggravated by intraperitoneal hemoglobin, bile or whole blood plus bile, and also by intravenous dextran.

Animals↗

Islet transplantation to the renal subcapsular space in streptozotocin-diabetic rats. Long-term effects on insulin and glucagon secretion.

In previous studies on streptozotocin-diabetic rats, transplantation of 1,000 (but not of 400) pancreatic islets to the renal subcapsular space was followed within 10 days by near-normalization of the impaired insulin secretion and the hyperglycemia. The long-term effects were now studied by measuring insulin and glucagon secretion 3 months after transplantation of 1,000 collagenase-isolated islets in streptozotocin (70 mg/kg) diabetic rats. At this time, diabetic control rats showed marked hyperglycemia and hyperglucagonemia, whereas the basal glucose and glucagon levels had normalized in the transplanted rats. Furthermore, insulin secretion in response to glucose or arginine stimulation and glucagon secretion following arginine stimulation were normal in all transplant rats, but absent in all diabetic controls. Morphologically the transplanted islets in the renal subcapsular space appeared normal on hematoxylin-eosin staining and immunostaining with antisera directed against insulin, glucagon, somatostatin and chromogranin A/B. Thus the islet transplants normalized basal hyperglycemia and hyperglucagonemia and restored insulin and glucagon secretion on a long-term basis.

Animals↗

Insulin and glucagon secretion in streptozotocin-diabetic rats: influences of islets transplanted to the renal subcapsular space.

Two days after diabetes induction by streptozotocin 70 mg/kg i.v. in rats, 1,000 freshly hand-picked islets were transplanted to the renal subcapsular space. The insulin and glucagon secretory capacities were evaluated during the first 10 days after transplantation by the use of arginine infusion and glucose injection. Already at day 3 after transplantation, the basal hyperglycemia and hyperglucagonemia were markedly reduced. However, no plasma insulin response to arginine or glucose was observed in the transplanted rats, whereas the glucagon response to arginine exaggerated that both in the diabetic and in the healthy controls. At day 10 after transplantation, the plasma insulin response to arginine was significantly improved to that at day 3, but it was still lower than in controls. In contrast, the glucose-induced increase in plasma insulin levels was now normalized. Also the glucagon response to arginine was similar in the transplanted animals as in the healthy controls. In conclusion, (a) streptozotocin-diabetic rats transplanted with 1,000 freshly hand-picked islets to the renal subcapsular space had near-normal plasma insulin and glucagon responses to arginine and glucose already at 10 days after transplantation, (b) the insulin response to glucose seemed normalized prior to that of arginine, and (c) the basal hyperglucagonemia was normalized already at day 3 after transplantation, i.e., it was restored earlier than was the insulin response to arginine or glucose.

Animals↗

[Pathophysiologic principles of modern liver surgery].

Successful liver surgery depends on the regeneration of the liver. Most of our knowledge about regeneration stems from experimental studies in rats. While morphological regeneration occurs early more sophisticated functions such as bile salt production and bile salt conjugation takes a long time to normalize. A review is given of the many factors that contribute to regeneration. The object of most current interest is the role of fibronectin. After experimental hepatectomy the secretion of plasma fibronectin increases. This might be the single most important factor involved in hepatic regeneration.

Animals↗

Influence of splenectomy, partial splenectomy and splenic artery ligation on E. coli sepsis in rats.

Male Sprague-Dawley rats were allocated to four groups--sham operation, partial splenectomy, splenic artery ligation or total splenectomy, and 4 weeks after the operation 3 x 10(8) colony-forming units of Escherichia coli were injected intraperitoneally. Among the splenectomized rats the mortality was significantly (p less than 0.02) increased compared with the controls, while both partial splenectomy and splenic artery ligation did not influence survival. Blood clearance and organ (liver, spleen and lungs) uptake of intravenously injected, radiolabelled, heat-killed E. coli were determined 1 hour after the intraperitoneal challenge. Splenectomy caused a significant decrease in blood clearance. Splenic uptake of radiolabelled E. coli was significantly reduced following partial splenectomy and splenic artery ligation. The splenic operations increased hepatic uptake expressed per gram tissue. Splenectomy thus resulted in reduced blood clearance and increased mortality in Gram-negative sepsis, while the reduced splenic uptake following partial splenectomy or splenic artery ligation did not influence blood clearance of E. coli or mortality.

Animals↗

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↗

Surgery of hepatic metastases.

5-year survival after liver resection for colorectal liver metastases is 20-30%. Several factors contribute to a short survival: 4 or more liver tumours, a tumour free margin less than 10 mm and the occurrence of extrahepatic metastases. The prognosis is not significantly less in bilateral as compared in unilateral disease provided that 3 or less tumours, no extrahepatic spread at the tumour free margin more than 10 mm can be achieved. No prognostic difference is seen between synchronous and metachronous metastases.

Colonic 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↗

Major liver resection for hilar cholangiocarcinoma.

Between 1968 and 1984 liver resection with curative attempt was performed in 22 patients with hilar cholangiocarcinoma. Right lobectomy was performed in 4 patients, extended right lobectomy in 7, left lobectomy in 8, and excision of the median segment segment of the left lobe (segment IV) in 3. Bilio-enteric continuity was restored by hepatocholedochostomy in 17 patients and hepatojejunostomy in 4. (One patient had external transhepatic catheter drainage and no internal bile drainage.) Operative mortality rate was 27% and caused by excessive intraoperative bleeding, sepsis, or liver insufficiency. Postoperative complications occurred in 57% of patients surviving the operation and were due mainly to leakage from the hepatocholedochostomy. Median survival was 6 months, and one third of the patients survived 1 year. Three patients survived 10 years and were among the four patients in whom a tumor-free resection margin was obtained (one of them died in the postoperative phase). It is concluded that resection of hilar cholangiocarcinoma may give long-term survival if a free resection margin is obtained. The importance of a free resection margin indicates that surgery should be aggressive and include liver resection.

Adenoma, Bile Duct↗

The effects of pneumatic antishock garments in the treatment of critical abdominal injuries in rats.

Thirty rats were subjected to a standardized critical aortic injury and divided into six groups. In addition to controls, the animals were treated with a pneumatic antishock garment (PASG), massive intravenous or intra-aortic saline infusion, or PASG in combination with either massive intravenous or intra-aortic saline infusion. Twenty-six rats were subjected to a standardized hepatic injury and divided into four groups. In addition to controls, the animals were treated with PASG, massive intravenous saline infusion, or PASG in combination with massive intravenous saline infusion. These animals were allowed to bleed for 5 minutes before the treatment was started. The treatment with PASG alone prolonged the median survival time significantly from 7 min in the control group to greater than 120 min in the PASG group in rats with an aortic injury and from 33 to greater than 120 min in rats with a hepatic injury. Intravenous infusion of saline did not prolong the median survival time. Intravenous infusion in combination with PASG did not have any positive effects on median survival time or median mean aortic pressure and failed to prolong the median survival time significantly in rats with a liver injury, as six out of eight animals developed a lethal pulmonary edema.

Abdominal Injuries↗