[False safety with homeopathic agents. Swedes became ill with malaria in spite of prophylaxis].
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Publications and source records attributed to L Bergqvist.
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BACKGROUND: Conflicting results have been obtained regarding blood flow distribution to liver tumors. The emphasis on portal vein perfusion has had a great impact on the design of treatment protocols. METHODS: Double microsphere technique with reference organ sampling was used for the measurement of hepatic artery and portal vein blood flow of an implanted liver tumor in 42 rats after permanent dearterialization and repeated dearterialization (2 hours/day) compared with untreated sham-operated controls. RESULTS: Portal venous blood flow constituted 16% of total tumor blood flow and slightly increased after permanent and repeat dearterializations, though the elevation was not statistically significant as compared with sham-treatment (P > 0.05). In another 3 groups, the treatment was extended to 10 days, and tumor blood flow was measured in central and peripheral parts separately. Arterial blood flow further decreased in tumor periphery and was still lower in the tumor center (P < 0.01 versus tumor periphery), and portal blood flow declined concomitantly to 4% of total tumor blood perfusion. However, no difference in portal blood flow between the tumor center and periphery could be demonstrated (P > 0.05). Furthermore, portal supply increased neither in tumor periphery nor in tumor center after both permanent and repeated dearterialization (P > 0.05). CONCLUSION: The authors' results showed that portal blood flow did contribute to tumor circulation, but made up only 16% of blood flow when tumors were small and declined to 4% of entire tumor blood supply when tumors became large. Portal perfusion also declined as tumors grew larger and did not compensate for the withdrawal of tumor arterial blood supply after dearterialization.
Repeat dearterializations seem to be a means to prevent collateral formation, which is partly responsible for the failure of hepatic artery ligation (HAL) or permanent dearterialization when used to treat liver tumors. In this study restoration of tumor blood flow was evaluated after various procedures: HAL (n = 12), permanent dearterialization (n = 18), repeated dearterializations for 2 hr/day (n = 12), and sham dearterialization (n = 12). Tumor blood flow was measured 10 days after sham dearterialization, permanent dearterialization, and repeated dearterializations for 2 hr in order to further illustrate the effect of prolonged dearterialization on tumor rearterialization. Hepatic and tumor arterial blood flow was measured using the reference organ method (NEN, 141Ce microspheres with diameter 15 microns). Our results showed that during a transient dearterialization blood flow decreased to 1% (0.01 +/- 0.01 ml/min/g) of the flow in the controls (0.82 +/- 0.10 ml/min/g) (P < 0.01). After HAL tumor blood flow recovered to initial levels after 48 hr (0.73 +/- 0.17 ml/min/g). Even in rats subjected to a permanent dearterialization blood flow was reestablished at Day 6 (0.59 +/- 0.21 ml/min/g). In contrast, after repeat daily 2-hr dearteralizations blood flow remained significantly very low during the 6th transient dearterialization (0.11 +/- 0.03 ml/min/g) compared with both sham-operation and HAL as well as permanent dearterialization (P < 0.01). During the 10th daily dearterialization tumor blood flow was still significantly low compared with both controls (P < 0.001) and permanent dearterialization (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
In many nuclear medicine applications a well defined particle size and stability of administered colloids is of great importance. A fast and reliable sizing technique for routine quality control is therefore essential. This paper evaluates autocorrelation spectroscopy with an instrument capable of analysing several peaks simultaneously. A total of nine 99mTc-labelled colloids and one 99Y-labelled colloid were studied. The autocorrelation spectroscopy measurements were compared with the standard sizing technique of microfiltration. A good agreement between the sizing techniques was found for most of the colloids. The reproducibility of successive measurements was within +/- 12% and +/- 40% when using unimodal analysis and SDP analysis, respectively. Autocorrelation spectroscopy was found to be well suited for particle sizing and stability tests of radiolabelled colloids.
The scintigraphic technique to investigate the lymphatic system is based on a good knowledge of basic criteria in order to correctly interpret the findings. This article penetrates these criteria, updates the present knowledge, and covers basic science work and clinical applications. The anatomy, physiology, and pathology of the lymphatic system are covered. Basic criteria for the radiopharmaceuticals to be used are described as well as their quality control. The principles for lymphoscintigraphy are described. The dosimetry in lymphoscintigraphy as well as radiation risk is estimated for different procedures. Experimental animal studies are summarized. Clinical applications cover staging procedures for breast cancer, malignant melanoma, pelvic neoplasms, and lymphoma. Lymphadenoectomy follow-up studies are also included. The use of lymphoscintigraphy in radiotherapy dose planning is described as well as lymphatic function studies in, e.g., edema and lymph transplantations.
Hepatic reticuloendothelial function was measured in 6 experimental groups of rats with various portasystemic shunts or total liver arterialization by computer calculation of the hepatic uptake rate of intravenously injected 99mTc-sulphur colloid. Marked reduction of the hepatic reticuloendothelial system (RES) function was found both 1 and 3 weeks after the construction of a mesentericocaval or conventional end-to-side portacaval shunt. Hepatic RES function was also lowered both 1 and 3 weeks after a modified portacaval shunt, but the reduction was much less pronounced. Total liver arterialization produced a similar mild reduction of hepatic RES function after 1 week; however, there was no longer any significant reduction after 3 weeks. This study concludes that total liver arterialization ameliorates the negative effect that portasystemic shunting has on hepatic RES function.
The [99mTc]sulfur colloid distribution in rat organs was investigated after the administration of different amounts of colloid particles. Saturation of the liver and spleen was not observed. Blood clearance was significantly reduced 15 min after injection above approximately 3 X 10(9) particles per kg body weight. With an increasing number of injected particles, lung uptake increased and bone marrow uptake decreased. Microfiltration studies showed that the colloid is unaffected by dilution with saline but may be affected after incubation in normal rat plasma. We conclude that the distribution of [99Tc]sulfur colloid in organs varies with the number of injected particles and therefore, is not dependent upon the blood flow to the reticuloendothelial organs alone. The "critical colloid dose" may differ among the reticuloendothelial organs and cannot, therefore, be evaluated by blood clearance measurements alone. The considerable influence of the number of injected colloid particles on bone marrow uptake should also be recognized when carrying out dosimetric calculations.
Studies of the activity uptake of radiolabelled 99mTc2S7 colloid in different tissues showed a moderately increased uptake in the lung 1 week and a greatly increased uptake 3 weeks after permanent bile duct occlusion. Three weeks after bile duct occlusion the activity uptake was also slightly increased in the spleen and moderately reduced in the liver. In pulmonary tissue of cholestatic rats, the levels of alkaline and acid phosphatase, beta-glucuronidase, and beta-hexosaminidase were determined after 6 weeks. The pulmonary contents of beta-glucuronidase was increased tenfold, and that of beta-hexosaminidase was increased fourfold in cholestasis. Histochemical investigation showed that the lysosomal enzymes were located in the macrophages, which in cholestasis were abundant in alveolar walls and inside alveoli. Macrophages were also frequently seen to engorge pulmonary veins.
Reticulo-endothelial function was evaluated by measuring the biokinetics of a standardized 99mTc-sulphur colloid using scintillation camera technique in rats with biliary obstruction. There was no difference in the uptake of the colloid in the liver (K1) between sham operation and biliary obstruction at 1 week and 3 weeks. However, when corrected for changes in liver volume, the corrected colloidal uptake rate (cK1) of the liver was significantly decreased in 1 week's biliary obstruction (P less than 0.005 compared with sham operation) and 3 weeks' biliary obstruction (P less than 0.025 compared with 1 week obstruction). Colloidal uptake rate of the extrahepatic reticulo-endothelial system (K2) was significantly increased (P less than 0.005) in rats with 3 weeks' biliary obstruction. Activity distribution of 99mTc-sulphur colloid in 3 weeks' biliary obstruction was significantly decreased in both total organ basis and per gram basis (P less than 0.005). The results demonstrated a depression of RE activity of the liver in biliary obstruction.
Reticuloendothelial (RE) function was evaluated by measuring the biokinetics of a standardized 99Tcm-sulphur colloid. Methyl palmitate was administered intravenously on two consecutive days. A statistically significant reduction in the colloid uptake rate of the liver was registered after methyl palmitate administration. Histological examination revealed no signs of destruction of RE cells or microembolization. Inoculation of an experimental nitrosoguanidine-induced transplantable adenocarcinoma to the liver was performed in 16 rats one day after methyl palmitate administration and in 16 controls. Tumor size was significantly larger in methyl-palmitate-treated animals at 7 and 14 days after inoculation. Survival was significantly decreased in methyl-palmitate-treated rats. These rats showed signs of fatty vacuolization and necrosis of liver parenchyma earlier than controls. Analyses of beta-hexosaminidase and lactate dehydrogenase revealed no deviation of enzyme levels either before or after tumor inoculation. The results indicate that a temporary suppression of RE function at the time of tumor inoculation may influence subsequent tumor growth.
Lymphoscintigraphy using 99mTcSb2S3 colloid was performed in 32 patients with malignant melanoma. Subcutaneous injections were made peritumorally in 20 patients and dorsopedally in 12 patients. Regional lymph node dissections were carried out on the following day in 16 patients and the resected lymph nodes were weighted, measured for radioactivity, and examined by light microscopy. Lymph flow to regional lymph nodes was shown in all but 2 patients. Twenty-nine of 239 lymph nodes contained metastases. Radioactivity was demonstrated in 17 of these nodes. In 5 of 11 patients with metastatic disease, the highest uptake was found in cancerous lymph nodes. The specific activity-uptake distribution in isolated ilio-inguinal lymph nodes after a dorsopedal injection was log-normal with a mean of 0.05%/g indicating a good saturation of colloid particles. This investigation concludes that the observed lymph flow directions in patients injected peritumorally are of value for the follow-up. Quantitative lymphoscintigraphy in patients with melanoma of the lower extremities is, however, of no value for excluding ilio-inguinal lymph node metastases.
Plasma levels of a lysosomal enzyme, beta-hexosaminidase (beta-N-acetylglucosaminidase, EC 3.2.1.30) were studied in Wistar rats after administration of 99mTc -sulfur colloid, 198Au colloid, gelatine (Haemaccel), alcohol, methylpalmitate and zymosan. The activity of beta-hexosaminidase was increased 10, 30 and 60 min after the zymosan injection. After 24 and 48 h, enzyme levels had returned to those at outset. The transient release of beta-hexosaminidase probably occurred only during the phagocytosis of zymosan which was evaluated by histological examination of lung, liver and spleen. After the injection of all other agents tested, no significant aberration of beta-hexosaminidase levels was seen. Activity distribution of the radio-labeled colloids revealed differences in organ uptake which were attributed to a difference in colloid particle size. Although the colloids tested have been used extensively for determination of reticuloendothelial function and histological studies suggest phagocytosis of the particles, their administration did not affect plasma beta-hexosaminidase levels. Since lysosomal enzymes are cleared from the blood predominantly by liver macrophages, the primary location of particle phagocytosis may explain the present findings.
The bone-imaging agents MDP, DPD and HDP were compared radiochemically (only minor differences were found) in 12 patients with prostatic and 12 patients with breast carcinoma. Each patient received both MDP and either DPD or HDP. The scintigraphic examinations were compared visually and quantitatively. The uptake ratio normal bone/soft tissue was higher for DPD and HDP than for MDP. The ratio pathologic bone/normal bone was highest for MDP, particularly for prostatic carcinoma. The differences in this ratio for breast carcinoma were in general non-significant. The observed differences were minor and of little practical importance.
The function of the reticuloendothelial system (RES) was evaluated after the inoculation of an experimental tumor in rats. Four groups were studied according to tumor size and site. Reticuloendothelial function was evaluated by measuring the biokinetics of a standardized [99Tcm]-sulfur colloid. Estimation of the uptake rate of the labeled colloid into the liver and other parts of the RES was performed through the use of a two-compartment model. Animals with small liver or subcutaneous tumors showed an increased activity of both the hepatic and the extrahepatic RES. Animals with large retroperitoneal tumors showed a significant decrease in the RE function of the liver. In these animals the function of the extrahepatic RES was not changed compared to controls but was, however, significantly decreased compared to animals with smaller tumors. The findings may reflect a difference in the impact of tumor size on RE function extra- and intrahepatically.
The biokinetics of inert lymphoscintigraphic agents strongly depends on their particle size. Different techniques for characterization of colloids are discussed. Experiments have been performed on eight different colloids. The particle size has been investigated with scanning electron microscopy. Activity distributions have been obtained with ultrafiltration and gel-column scanning technique. The colloids suggested for lymphoscintigraphy were found to have a median size of about 40-50 nm except one minimicro-aggregated human serum albumin colloid which has a median particle size around 10 nm. The biokinetics were studied with a scintillation camera in rabbits after a subcutaneous injection. Time-activity curves were generated. After 5 hr the rabbits were dissected and the activity content in different tissues measured. A compartment model for the biokinetics was designed and rate constants evaluated. The total and specific activity uptake in parasternal lymph nodes was highest for the small-particle colloids. The compartment model showed a good fitting to the experimental data.
A quantitative kinetic technique using a scintillation camera has been developed for investigating lymph drainage and the uptake in the lymph nodes of 99mTcSb2S3 colloid injected subcutaneously. Twenty-two patients with primary malignant melanoma were examined. Lymph-node dissection was performed and 185 lymph nodes were individually measured for radioactivity. The kinetics of colloid uptake in individual nodes can be expressed by a simple two-compartment model. The outflow of colloid from the injection site was found to be monoexponential, and the tissue volume containing the injected colloid at the injection site increased asymptotically with time. A model has been developed for calculating absorbed doses at the injection site and in organs with colloid uptake. The following absorbed doses were estimated (muGy/MBq): whole body 0.7-4.5, gonads 0-22, liver 1.0-3.9, lymph nodes up to 1000 and injection site about 10,000. Possible biological effects in the skin and effective dose equivalents have been estimated when using other lymphoscintigraphic agents.
Increased fecal blood loss was produced in healthy volunteers by the administration of two nonsteroidal anti-inflammatory drugs (NSAID), naproxen or fenflumizole. Basal as well as drug-induced gastrointestinal blood loss was measured using 51Cr erythrocyte labeling. Median rise in daily fecal blood loss was 432%. All subjects were endoscoped at the initiation and at the completion of the study. Endoscopic findings were assessed quantitatively by two observers in two different ways. All subjects but three had gastric mucosal lesions at follow-up endoscopy. There was a good correlation between the endoscopic assessments but no statistical correlation between the endoscopic assessment and the increase in fecal blood loss. The data suggest that factors other than gastric mucosal lesions have to be taken into account when investigating NSAID-induced gastrointestinal bleeding.