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Biomedical subjects

U Stenram

Publications and source records attributed to U Stenram.

At least 37 records · Page 2Linked to original sources

Interstitial laser treatment of malignant tumours: initial experience.

This is a prospective pilot investigation of interstitial laser treatment. Twelve patients were treated at 13 sites: seven patients had metastatic or primary liver cancer (with a total of 21 tumour nodules), two had pancreatic carcinoma and four patients had disease at other sites. Treatments were performed with an Nd-YAG laser, using a high power (6 or 10 W), short-time (5 min) technique or a feedback system for temperature regulation at low power (3 W) for 12-16 min. Treatment with high power invariably resulted in rapid carbonization of tissue, which may have contributed to the postoperative death in one patient. The local effect of treatment could be evaluated in 13 hepatic tumours (1.0-10 cm in diameter): 100% necrosis was seen in five and >50% necrosis in the remaining eight. Two tumours were eradicated, five became smaller, and six remained unchanged in size or showed continued growth. Treatment removed or alleviated symptoms in 7/8 symptomatic patients. The feedback system made it possible to avoid carbonization and allowed better control of the tissue temperature. The main problem with either method was to monitor tissue changes in real time, and ultrasonography was found to be of little help in this respect. It is concluded that interstitial laser treatment is a promising method for treatment of tumours. Further development should focus on real-time monitoring and increased volume effect without carbonization.

Aged↗

Photodynamic therapy using intravenous delta-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats.

The efficacy of photodynamic therapy (PDT) using delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour cells through the portal vein in rats. ALA at a dose of 60 mg kg(-1) b.w. was intravenously administered 60 min before PDT. PpIX accumulation in tumour, normal liver and abdominal wall muscle was detected by means of laser-induced fluorescence (LIF). Laser Doppler imaging (LDI) was used to determine changes in the superficial blood flow in connection with PDT. Histopathological examinations were performed to evaluate the PDT effects on the tumour and the surrounding liver tissue, including pathological features in the microvascular system. The accumulation of PpIX, as monitored by LIF, showed high fluorescence intensities at about 635 nm in both the hepatic tumour tissue and normal liver and low values in the abdominal wall. LDI demonstrated that the blood flow in the treated tumour and its surrounding normal liver tissue decreased immediately after the PDT, indicating an effect on the vascular system. A large number of thrombi in the irradiated tumour were found microscopically 3 h after the PDT. The tumour growth rate showed a marked decrease when evaluated 3 and 6 days after the treatment. These results show that the ALA-PDT is effective in the inhibition of growth of experimental hepatic tumours.

Aminolevulinic Acid↗

The effects of Lactobacillus strains and oat fiber on methotrexate-induced enterocolitis in rats.

BACKGROUND & AIMS: Administration of methotrexate to rats on an elemental diet results in severe enterocolitis and death. Lactobacilli, an integral part of the healthy gastrointestinal microecology, may provide therapeutic benefits to help the recovery from enterocolitis. The purpose of this study was to evaluate the effects of lactobacilli and oatbase on methotrexate-induced enterocolitis in rats. METHODS: Rats received continuous intragastric infusion of elemental diet or with supplementation of oatbase, Lactobacillus reuteri R2LC, and Lactobacillus plantarum DSM 9843, with and without fermentation, from the beginning of the study. Methotrexate (20 mg/kg) was injected intraperitoneally on day 3, and the sampling was performed on day 6. RESULTS: Lactobacilli and oatbase decreased body weight loss and intestinal permeability and increased bowel mucosal mass in enterocolitic rats. Administration of lactobacilli, but not oatbase, decreased the intestinal myeloperoxidase level, reestablished intestinal microecology, and reduced bacterial translocation to extraintestinal sites. Both lactobacilli and oatbase reduced plasma endotoxin levels. The effects of lactobacilli were greater with fermentation than without fermentation or oatbase alone, and L. plantarum was more effective in reducing intestinal pathogens than L. reuteri. CONCLUSIONS: Exogenous administration of lactobacilli, especially L. plantarum with fermentation, is helpful in reducing the severity of enterocolitis in rats.

Animals↗

Pectin-supplemented enteral diet reduces the severity of methotrexate induced enterocolitis in rats.

BACKGROUND: Administration of methotrexate (MTX) to rats fed an elemental diet results in a high mortality from severe enterocolitis. Previous studies have shown that pectin is an important precursor of substrates for intestinal structure and function and may facilitate intestinal recovery after enterocolitis. The aim of this study is to evaluate the effect of pectin on MTX-induced enterocolitis in rats. METHODS: Rats received intragastric infusion of either 1% pectin-supplemented or pectin-free elemental diet from the beginning of the study via a gastrostomy. On the 4th day animals received either MTX, 20 mg/kg intraperitoneally, or saline injection and were killed on the 7th day for sampling. RESULTS: Pectin supplementation significantly decreased body weight loss, organ water content, and intestinal myeloperoxidase levels and increased mucosal protein, DNA, and RNA content in enterocolitis rats. The intestinal permeability was increased by administration of MTX, and pectin supplementation significantly reversed the increased permeability in the distal small bowel and colon. Pectin supplementation also lowered the magnitude of bacterial translocation, decreased plasma endotoxin levels, and restored bowel microecology. CONCLUSIONS: Pectin significantly decreased MTX-induced intestinal injury and improved bowel integrity.

Animals↗

Tumour S-phase activity, nucleotide profile and RNA levels after hepatic artery occlusion and reperfusion in an experimental model of secondary liver carcinoma.

Rats with carcinoma of the colon implanted into the liver were subjected to hepatic arterial occlusion for 30-120 min. Regrowth of the tumour after reperfusion was evaluated by immunohistological determination of S-phase activity after injection of bromodeoxyuridine. Levels of RNA and nucleotides, and energy charge, were also examined. DNA synthesis was observed in the entire tumour except in necrotic areas of controls and after 30-min ischaemia with 2-h reflow. Almost all tumoral DNA synthesis was abolished by 2 h of ischaemia, except in a few cells in the tumour periphery, which after reperfusion for 22 and 40 h grew into a band-like concentric layer. Levels of energy charge, adenosine, uridine and guanosine 5'-triphosphates, and RNA were unchanged in liver tissue after hepatic arterial occlusion but decreased in the tumour. In conclusion 30 min of ischaemia did not damage the tumour cells substantially. Ischaemia for 2 h seemed able to kill the tumour cells except those in the periphery in areas nourished by the portal vein where tumour regrowth was seen. The liver tissue was not damaged.

Animals↗

Differential expression of uPA in an aggressive (DU 145) and a nonaggressive (1013L) human prostate cancer xenograft.

Prostate cancer has a slow growing noninvasive phase, but, in general, is invasive on diagnosis. An initial step in the invasion of surrounding normal tissue is the activity of proteolytic enzymes such as components of the plasminogen activator system (PA). In cell culture, the primary human prostate cancer cell line 1013L expressed no urokinase type-PA (uPA), while DU 145, a cell line derived from a metastatic lesion, expressed high levels of uPA. The DU 145 cells grew easily as xenografts but the establishment of 1013L in the SCID mice was possible only with the aid of a gelatin sponge (Spongostan). The latency period was 42-64 days, followed by a slow growth phase before a fast growth phase occurred. This fast growth phase was characterized by rapid degeneration of tumor tissue, while high proliferation occurred around the blood vessels. On serial transplantation of tumor material, the growth pattern was similar. Furthermore, the 1013L tumor was encapsulated by connective tissue and no invasiveness could be detected. We found that 1013L tumor homogenates had hardly detectable levels of uPA, i.e., 300-fold lower than we found in the invasive prostate xenograft DU 145. In addition, no expression of uPA was found in the plasma of 1013L tumor-bearing mice whilst uPA antigen was detected in the plasma of DU 145 tumor-bearing mice. In conclusion, the 1013L cell line, which exhibits a nonaggressive pattern, could be a good model for studying progression of prostate cancer to a more aggressive phenotype in vivo and in vitro.

Animals↗

Influence of zymosan (a non-specific macrophage stimulator) and of indomethacin on liver tumours--an experimental study in rats.

Zymosan--a non-specific macrophage-stimulating agent--reduces tumour take in the liver. The mechanism for this effect is not clear, but it may be mediated via the Kupffer cells and prostaglandins. On the other hand, the Prostaglandin-synthesis inhibitor, indomethacin, inhibits tumour growth. Pretreatment with zymosan (3 mg 100 g-1) for 3 days of two different strains of rats, inoculated in the liver with a hepatoma or an adenocarcinoma cell suspension respectively, reduced tumour take and also initial tumour growth. The effect on tumour take and initial growth was inhibited by concomitant administration of indomethacin (0.2 mg 100 g-1). When zymosan was administered after tumour cell inoculation the growth rate of the hepatoma was retarded, but this effect was not abrogated by indomethacin. Pretreatment with indomethacin had no significant effect on tumour take or initial growth. When given after the tumour was established in the liver, indomethacin reduced the growth rate of the hepatoma, but not of the adenocarcinoma. These results suggest that there are different mechanisms for the effects of zymosan on tumour take and on growth of an established tumour. In immunoincompetent nude mice the effect on the hepatoma was similar to the effect in the rat. In vitro both tumours were insensitive to zymosan and indomethacin. This study confirms that pretreatment with a non-specific macrophage stimulator (zymosan) diminishes tumour take and growth in the liver, that the effect of zymosan on tumour take in the liver is abrogated by indomethacin and that the zymosan effect on tumour take in the liver is at least partly mediated by the Kupffer cells and prostaglandins.

Adenocarcinoma↗

Intra-operative laser-induced photodynamic therapy in the treatment of experimental hepatic tumours.

OBJECTIVE: To examine the effect of photodynamic therapy (PDT) on experimental liver tumours in rats. DESIGN: An experimental liver tumour model was used. Each of a group of rats had two tumours simultaneously inoculated into its liver. The tumour located in the left hepatic lobe was used for PDT, and the other one, in the median lobe, as a control. The haem precursor delta-amino laevulinic acid (ALA), at a dose of 30 mg/kg body weight, was injected 60 min before laser irradiation. Rats in group I received ALA through a femoral vein. Those in group II received ALA through the portal vein. Group III had an injection of ALA solution through the portal vein plus hepatic inflow occlusion. Three and 6 days after the treatment, the rats were killed, and the tumours were measured, and ultrastructural changes were examined using scanning electron microscopy. SETTING: Lund University Medical Laser Centre, Lund, Sweden. RESULTS: The mean tumour volume of the treated tumours increased by factors of 1.9, 1.5 and 1.7 in groups I, II and III, respectively, compared with the pretreatment baseline value. However, the mean tumour volume in the control tumours increased by factors of 9.5, 4.3 and 4.8 in the respective groups. Under the light microscope, marked necrosis of the treated tumour and the surrounding liver tissue was observed. Scanning electron microscopy revealed heavy damage to the cells and vessels in the treated tumour. CONCLUSION: PDT with ALA is an effective treatment modality for rat liver tumours.

Aminolevulinic Acid↗

Influence of portal branch ligation on the outcome of repeat dearterializations of an experimental liver tumor in the rat.

It has been suggested that the portal vein should be occluded during intermittent hepatic dearterialization in order to induce a more complete ischemia of the tumor. In this experiment the influence of portal branch ligation in combination with repeat dearterializations on a liver tumor was investigated. Twenty-seven rats were randomly allocated to sham treatment (n = 6); portal branch ligation (PBL) (n = 7); 120 min of repeat dearterialization (n = 7); and portal branch ligation (PBL) in combination with 50 min of repeat dearterialization (n = 7) (once a day during 5 days). The results showed that portal branch ligation alone did not alter the tumor growth compared with sham treatment (P > 0.05), nor did portal branch ligation in combination with repeat dearterializations for 50 min (P > 0.05). However, tumor growth delay was achieved following 120 min of repeat dearterializations without occlusion of the portal branch (P < 0.01 versus all the other groups). There was a significant weight loss of the lobe undergoing PBL, whether dearterialization was added or not (P < 0.001). The liver nucleotide/DNA and RNA/DNA ratio significantly decreased as well. Histological examination showed that > 50% of tumor cells became necrotic after repeat dearterializations for 2 hr indicating a significant damage to tumor tissue. In contrast, PBL in combination with repeat dearterializations for 50 min induced extensive liver necrosis without having any influence on tumor growth.

Analysis of Variance↗

Early development of suture holding capacity in vascular anastomoses in the rat.

Early development of suture holding capacity (SHC) of end-to-end anastomoses in the infrarenal aorta and inferior vena cava (IVC) of the rat was studied by measuring the resistance to tensile forces at 0, 3, 5, 8, 11, or 14 days postoperatively. Comparable anastomoses were histologically evaluated. The SHC of the aortic wall decreased following anastomoses and did not regain the strength of nonanastomosed vessels during the first two weeks. The SHC of the IVC also decreased following anastomoses, but regained the strength of nonanastomosed vessels by the 5th day. The relative ultimate strain of the arterial and venous perianastomotic walls decreased slightly, while the relative compliance increased in the aorta and decreased in the IVC. Perianastomotic media necrosis was found exclusively in the arteries. The reduced perianastomotic SHC in the aorta indicates impaired healing, compared to the IVC. Changes in biomechanical properties of the aortic wall following anastomosis may increase its susceptibility to anastomotic complications such as pseudoaneurysms.

Anastomosis, Surgical↗

Photodynamic therapy of non-melanoma malignant tumours of the skin using topical delta-amino levulinic acid sensitization and laser irradiation.

Eighty basal cell carcinomas (BCCs) in 21 patients, 10 lesions of Bowen's disease in three patients, and four lesions of cutaneous T-cell lymphoma in two patients, were treated with photodynamic laser therapy (PDT), using topical application of the haem precursor delta-amino levulinic acid (ALA). The diagnoses were confirmed histologically prior to treatment. Fifty-five of the BCCs were superficial lesions, and 25 were nodular. Of the 80 BCCs, 39 (49%) were located on the trunk, 36 (45%) on the head and neck region, four (15%) on the leg and one on the arm. The two principal locations of the 10 Bowen's disease lesions were the leg (50%) and the trunk (40%). The T-cell lymphoma lesions were located on the shoulder and on the arm. A water-in-oil based cream containing 20% ALA was applied to the lesions, with a margin of about 10-20 mm beyond the visible tumour border, 4-6 h before the laser procedure. During this period of time the highly fluorescent and photodynamically active substance protoporphyrin IX (Pp IX) is synthesized via the haem cycle. Laser-induced fluorescence (LIF) was used for real-time monitoring of the Pp IX distribution in the tumour and in the normal surrounding skin, before and after treatment in all patients. Before laser treatment the Pp IX distribution demonstrated by LIF showed a demarcation between tumour and normal skin of about 15:1 for BCC and Bowen's disease, and 5:1 for T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Lysosomes and human liver disease: a biochemical and immunohistochemical study of beta-hexosaminidase.

Liver biopsies from 88 patients with different liver diseases were studied for beta-hexosaminidase activity. Liver specimens with normal light microscopical morphology showed no immunohistochemical reactivity for beta-hexosaminidase. Increased reactions were noted, mainly in hepatocytes, in biopsies from the patients with different liver diseases. A very large interindividual variation of biochemical liver beta-hexosaminidase activity occurred even within the same diagnostic group, and no group of patients showed any significant increase of liver beta-hexosaminidase activity compared with the patients with normal liver histology. Livers with positive immunohistochemistry showed increased biochemical values for beta-hexosaminidase. In patients with cholestasis due to alcohol abuse, the immunohistochemical reaction was intense and the biochemical beta-hexosaminidase activity was significantly increased compared with non-alcoholic cholestatic cases. Furthermore, blood samples taken from 50 patients at the same time as the liver biopsies. These patients showed significantly increased serum beta-hexosaminidase activity compared with normal controls, but no correlation was found between beta-hexosaminidase activities in the liver and serum of these patients.

Adolescent↗

The effects of tumour necrosis factor alpha on the vascular bed and blood flow in an experimental rat hepatoma.

The influence of TNF alpha on tumour growth rate has been attributed to its effects on the vascular bed and blood flow. The aim of our study was to investigate the effects of pharmacological doses of TNF alpha on the tumour vascular bed and to quantify blood flow in an experimental hepatoma during a more extended period after TNF-alpha exposure than hitherto reported. In Lister rats, a syngeneic rat hepatoma was implanted on the dorsum of the right hind foot. TNF alpha was given i.v. The injection was repeated after 24 hr. Tumour blood flow was estimated before and 1, 24, and 96 hr after TNF-alpha administration with the 133Xe-washout technique. The passage of microspheres through the tumour vascular bed (non-entrapment), as a measure of vascular occlusion, was estimated 4 and 96 hr after TNF-alpha administration. Tumour growth rate was measured. The tumours were subjected to histological examination and the sensitivity to TNF alpha in vitro was tested. A reduction of tumour blood flow was observed in TNF-alpha-treated groups. Tumour growth rate was equally increased after 96 hr in both the TNF-alpha groups as compared with controls. There was no significant change in non-entrapment for the TNF-alpha-treated rats as compared with controls. Histology revealed extensive necrosis and thrombosis in tumours. TNF alpha had no effect on the viability of the cloned hepatoma cell line in vitro.

Animals↗

Relation between the incorporation of 5-fluorouracil into liver carcinoma and normal tissue RNA at hepatic arterial administration in the rat is altered by overnight starvation.

The cytotoxicity of 5-FUra has been related to its incorporation into RNA. In a model of secondary liver cancer in the rat, the incorporation of 5-FUra into the acid-soluble fraction, RNA and DNA of several normal tissues and an adenocarcinoma of the colon transplanted to the liver was determined. A therapeutic labelled dose of the drug was infused via the hepatic artery for 2 hr and the rats killed 1 hr later. Half of the rats were starved overnight before treatment. The incorporation of 5-FUra into liver and intestinal RNA increased at starvation. It was unchanged in kidney and bone marrow. The incorporation into tumor RNA decreased insignificantly. The incorporation into tumor RNA was significantly higher than in hepatic, intestinal, and renal RNA at ad libitum feeding. This difference disappeared at overnight starvation.

Adenocarcinoma↗

Sclerotherapy of edematous gallbladders with different agents. An experimental study in pigs.

Different sclerosing agents were tried in experiments with 32 pigs to achieve ablation of gallbladders rendered edematous by mechanical lithotripsy with the Rotolith lithotriptor. In 16 pigs sclerotherapy was performed with 6% acetic acid, Carnoy's solution, 95% ethanol + 3% sodium-tetradecylsulfate (STS) and hot metrizoate, respectively. These animals were sacrificed immediately after the procedure. Histologic examination showed persistent surface epithelium and glandular epithelium in all specimens. In 6 pigs, the sclerotherapy was done with Carnoy's solution, 95% ethanol + 3% STS and hot metrizoate, respectively, and the pigs were killed 6 days later. Fibrosis of the gallbladder remnants was seen in these animals, but also remnants of surface and glandular epithelium. Hot metrizoate was used in another 10 pigs and these animals were sacrificed after 8 weeks. At histologic examination fibrosis was seen in the gallbladder remnants of 9 surviving animals, but also areas of preserved muscular layer, and development of mucinous cysts were found in more than 50% of the specimens. Thus, none of the sclerosants was able to produce a total ablation of the gallbladder mucosa.

Animals↗

Electrolytic stents to inhibit tumor growth. An experimental study in vitro and in rats.

Obstruction of metallic stents used in the management of malignant biliary strictures is common and in several cases due to tumor growth through the stent wall. In an experimental animal model in rats, a tumor was implanted subcutaneously adjacent to different metallic stents. Ingrowth of tumor through the wall of these stents was frequent. A stent generating direct electric current on the basis of electrolysis was developed and tested in vitro and in the experimental model. The study confirms that an "electrolytic" stent can inhibit ingrowth of tumor.

Animals↗