Monitoring isotretinoin therapy in thyroid cancer using 18F-FDG PET.

Treatment with isotretinoin (13-cis-retinoic acid, 13-cis-RA) is a recent additional option in advanced, otherwise intractable differentiated thyroid cancers. The aim of this study was to evaluate fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) in the prediction and the monitoring of response to 13-cis-RA therapy. Twenty-one patients with advanced differentiated thyroid cancers were investigated using 18F-FDG PET and iodine-131 whole-body scans before and 3, 6 and 9 months after initiation of 13-cis-RA therapy. After 9 months, 13-cis-RA treatment was discontinued and imaging procedures repeated 3 months later. Average 18F-FDG uptake (SUV) decreased significantly during 13-cis-RA therapy but subsequently increased in five of eight patients after withdrawal of 13-cis-RA. 18F-FDG uptake (SUV) 3 months after onset of 13-cis-RA therapy was significantly lower in patients who developed increased 131I uptake in their tumour sites than in patients with no subsequent increase in 131I uptake. There was no relationship between serum thyroglobulin level on the one hand and simultaneously measured 131I or 18F-FDG uptake on the other hand. There was a tendency towards lower 18F-FDG uptake in tumour manifestations with a better outcome. Therefore, 18F-FDG PET at 3 months after the start of treatment promises to differentiate between those patients who will eventually benefit from 13-cis-RA and those who will not. In conclusion, these data indicate that 18F-FDG PET is a useful tool for the evaluation and monitoring of adjuvant therapy with 13-cis-RA in thyroid cancer.

Digital selenium radiography: detection of subtle pulmonary lesions on images acquired with and without an additional antiscatter grid.

OBJECTIVE: the objective of this ROC-study was to evaluate the diagnostic efficacy of images acquired with a grid in digital selenium radiography compared to that on images obtained with the integrated air gap only. MATERIALS AND METHODS: seven types of simulated lesions were superimposed onto an anthropomorphic chest phantom. Selenium radiography images were obtained either with or without an additional antiscatter grid. For images acquired with a grid either a similar or increased exposure level was used. Both normal and obese patients were simulated. RESULTS: When a grid was used with an equivalent detector dose and a higher exposure, diagnostic performance was significantly improved as compared to images obtained with only the air gap. ROC curve areas for mediastinal nodules and catheters were substantially higher for images acquired with a grid and the same exposure level compared to images obtained without a grid. However, detection of linear, net-shaped and reticulonodular structures in peripheral lung regions was significantly worse when a grid was used with an equivalent exposure level. Concerning the interpretation of images obtained from the normal and obese phantom models, no substantial differences were observed. CONCLUSION: a marked improvement in diagnostic performance could be achieved by means of the use of an additional antiscatter grid and an equivalent detector dose. However, when the same exposure was used, images acquired with the grid allowed a better detection of mediastinal structures although a worse performance was evident in radiolucent lung regions. Therefore, the routine use of a grid without increased exposure is not recommended.

Lipoprotein lipase in rats fed fish oil: apparent relationship to plasma insulin levels.

To investigate the role of lipoprotein lipase (LPL) and hepatic lipase in the triacylglycerol lowering effects of fish oil, rats were fed lard (L), corn oil (CO) or menhaden oil (MO) as the primary fat source in otherwise identical diets. After 2 weeks, soleus muscle LPL differed between groups (MO greater than CO greater than L). Hepatic lipase did not differ between CO- and MO-fed rats but was elevated in L-fed rats. Adipose LPL did not differ between diet groups. Total epididymal fat weight was reduced in MO-fed rats. There was a significant positive correlation between adipose tissue weight and plasma free fatty acids. MO-fed rats had lower plasma insulin levels. Insulin was directly correlated with plasma triacylglycerol and glucose, consistent with a hyperinsulinemic, insulin-resistant state in CO- and L-fed rats, and a protective effect with MO feeding. In addition, insulin was directly correlated with adipose LPL. A negative relationship between soleus muscle LPL and insulin approached significance. Soleus muscle LPL was significantly inversely correlated with triacylglycerol. The data indicate that increased skeletal muscle LPL, in response to MO or a MO-induced decrease in insulin, may contribute to the triacylglycerol-lowering effects of fish oil. Decreased fat weight and adipose LPL and increased soleus muscle LPL and decreased plasma triacylglycerol suggest a shift from fat deposition to oxidation with MO feeding. The lack of response of hepatic lipase to MO feeding suggests that this enzyme does not contribute to the fish oil-stimulated lowering of plasma triacylglycerol via hepatic reuptake of very low density lipoproteins or other triacylglycerol-rich lipoproteins.

Apparent inhibition of hepatic triacylglycerol secretion, independent of synthesis, in high-fat fish oil-fed rats: role for insulin.

Rats were fed Chow (C; low-fat control) or a purified high-fat (30% of calories) low cholesterol diet containing menhaden oil (MO), corn oil (CO) or lard (L) for 2, 4 or 6 weeks. Rats were killed after an overnight fast. MO-fed rats had a larger weight/body weight that was accompanied by a lower mg liver DNA/g liver but unchanged liver DNA/body weight, indicating that hepatomegaly in the MO-fed rats was due to cellular hypertrophy. MO-feeding prevented the rise in plasma triacylglycerol and cholesterol observed with the other high-fat diets. There was a marked progressive accumulation of total liver triacylglycerol in the MO- and CO-fed rats. Plasma insulin was reduced in the MO-fed rats relative to all other groups. There were strong positive relationships between plasma insulin and triacylglycerol and between insulin and cholesterol in the high-fat-fed rats. Total liver glucose-6-phosphate dehydrogenase and malic enzyme activities were reduced by MO-feeding and were directly correlated with plasma cholesterol and insulin. These data are consistent with an apparent inhibition of hepatic triacylglycerol secretion by high-fat fish oil-feeding that is independent of the inhibitory effects on triacylglycerol synthesis. These data suggest a role for insulin in regulating the plasma triacylglycerol and cholesterol concentrations in MO-fed rats.

Improved survival of heterotopic cardiac allografts in rats with dietary n-3 polyunsaturated fatty acids.

A heterotopic cardiac transplant model, with male Fischer 344 rats as donors and Long Evans rats as recipients, was utilized to investigate the effect of dietary n-3 polyunsaturated fatty acids on acute rejection. Both donor and recipient rats were fed purified diets high in either n-3 polyunsaturated fatty acids (from concentrated n-3 ethyl esters [EE] or fish oil [FO]) or n-6 polyunsaturated fatty acids (from corn oil [CO]) for either 2-3 or 3-4 weeks before transplant. The recipient rats continued on their diets until rejection. The AIN-76A-based diets (with 30% of calories as fat) had adequate essential fatty acids and were balanced for sterols and antioxidants. Allograft survival was significantly increased by 45% when recipient rats were fed EE as compared to the control (CO diet fed to both donor and recipient), regardless of the diet fed to the donor. There was a slight but significant increase in allograft survival when only donor rats were fed the EE diet 2-3 weeks before transplant. With the FO diet (containing one third of the n-3 fatty acids in the EE diet), only the group fed FO to both donor and recipient (starting 2-3 weeks before transplant) showed a significant increase in allograft survival over the control. However, if the FO diets were fed for 3-4 weeks before transplant, increased survival was seen in groups fed FO to either the donor or recipient alone. In this case, allograft survival with FO feeding to both donor and recipient was not different from recipient treatment alone. In all the studies there was a significant and direct correlation between allograft survival and the donor heart phospholipid n-3/n-6 fatty acid ratio and the n-3 fatty acid content (at rejection). There was an indirect relationship with the n-6 fatty acid content. There was no detectable 20:3 (n-9) in the cardiac phospholipids, indicating the absence of essential fatty acid deficiency. Recipient diets were the strongest determinant of the fatty acid composition in the transplanted donor heart. The data indicate that providing dietary n-3 polyunsaturated fatty acids before and after cardiac transplant to recipient animals provides a significant protection against acute rejection.

Basic fibroblast growth factor promotes in vitro survival and cholinergic development of rat septal neurons: comparison with the effects of nerve growth factor.

The effects of basic fibroblast growth factor and nerve growth factor on survival and transmitter expression of cultured rat embryonic (E18) septal neurons were studied. Two different culture media were used: (i) a horse serum-containing Leibowitz L-15 medium and (ii) a serum-free N1-supplemented Dulbecco's modified Eagle's medium. Addition of basic fibroblast growth factor to either culture medium enhanced neuronal survival in low density cultures after 4 days. The effects of basic fibroblast growth factor were dose-dependent and blocked by anti-basic fibroblast growth factor antibodies. In serum-containing L-15 medium nerve growth factor also promoted neuronal survival. Basic fibroblast growth factor and nerve growth factor supported neurons comprised both cholinergic and GABAergic subpopulations. The effects of basic fibroblast growth factor and nerve growth factor were not additive. In high density cultures using serum-containing L-15 medium survival of septal neurons was four times higher than in low density cultures after 4 days. Addition of basic fibroblast growth factor or nerve growth factor did not further augment neuronal survival in high density cultures. Maintenance of septal neurons at high density was not affected by antibodies to basic fibroblast growth factor and/or nerve growth factor. Addition of basic fibroblast growth factor or nerve growth factor to serum-containing L-15 medium at high cell density significantly enhanced choline acetyltransferase activity 3- and 7.5-fold, respectively, without affecting cell survival. In conclusion, next to nerve growth factor, basic fibroblast growth factor, which has been located in the hippocampal target area of septal neurons, appears to be another potent trophic factor for septal neurons.