Fetal liver and pancreas transplanted as a composite improves islet graft function.
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Biomedical subjects
Publications and source records attributed to L Tafra.
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Recently, composite grafts of hepatocytes and islets have been shown to improve the survival of hepatocytes. The possibility of a reciprocal effect of hepatocytes on islet function was investigated. Diabetic Lewis rats were isografted with (1) fetal pancreas and fetal liver (FP/FL), (2) fetal pancreas alone (FP), and (3) fetal pancreas and fetal spleen (FP/FS). Grafts were transplanted to the small bowel subserosa. All (6/6) FP/FL recipients were cured (glucose less than 250 mg/dl for greater than 30 days), whereas only 72% (13/18) of FP alone and 60% (3/5) of FP/FS recipients were cured. The amount of time to normoglycemia for FP/FS recipients was less (26 +/- 15 days) compared with FP (50 +/- 29 days) or FP/FS recipients (71 +/- 40 days). Mean glucose levels at 6 weeks were 166 +/- 78 mg/dl, 237 +/- 97 mg/dl, and 355 +/- 81 mg/dl in cured FP/FL, FP, and FP/FS recipients, respectively. Glucose tolerance test results were not significantly different from those of nondiabetic control rats. In contrast to FP alone, FP/FL recipients had well-granulated hyperplastic islets and hepatocytes on histologic examination. When new isograft recipients were treated with cyclosporine, all FP recipients remained hyperglycemic; however, 75% (6/8) of FP/FL recipients were cured. In conclusion, FL in a composite graft with FP resulted in better engraftment, earlier isograft function, and protection from cyclosporine islet toxicity.
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Topographically, there are both morphological and biochemical differences in the articular cartilage of the tibial plateau of normal adult dogs when the cartilage covered by the meniscus is compared with that more centrally placed and not covered by meniscus. Histologically, differences are present in the surface morphology, in intra- and extracellular lipid content, and in the morphology of the mineralization front. Electron microscopy shows, in the covered cartilage, variability in collagen fiber size, with evenly spaced fibers apparently randomly distributed and an orderly relationship between the proteoglycans and collagen, whereas in the uncovered area, the collagen is aggregated into bundles and appears to be dissociated in large part from the proteoglycans. The most striking feature in the biochemistry of the two regions is an increased water content in the uncovered cartilage, as compared with the covered. In addition, there is an increased amount of proteoglycans that can be extracted in the uncovered cartilage. The heterogeneity of the cartilage on the tibial plateau should be taken into account when considering both the histologic and biochemical variations found in osteoarthritic cartilage; and when reflecting on the pathogenesis of osteoarthritis.
BACKGROUND: Lymphatic mapping with sentinel node biopsy is becoming a standard diagnostic test for melanoma and is being extensively investigated for use with other soft tissue tumors. Both filtered and unfiltered technetium sulfur colloid (Tc 99) have been used for preoperative lymphoscintigraphy, as well as intraoperative lymphatic mapping, and it is not clear if one is preferable over the other. The purpose of this study was to compare these two preparations to determine whether the form of Tc 99 used affects the results of lymphatic mapping. METHODS: Mock skin sites were placed on each extremity of 12 domestic pigs totaling 48 skin sites. Twenty-four of the lesions were injected with unfiltered Tc 99; the remaining 24 were injected with Tc 99 passed over a 0.2-microm filter. Both preparations of Tc 99 were mixed with 1 mL of isosulfan blue before injection. Sentinel node dissection was performed using a gamma probe, with counts recorded over a 10-second period and timed to begin 5 minutes after injection. RESULTS: Sentinel nodes were identified in all 48 lymph node basins draining the mock sites and characterized as hot (10x background), blue, or both. Significantly more sentinel nodes were found in the filtered (105 total, X = 4.4/basin), than in the unfiltered group (total 53, X = 2.2/basin, P <.0001). The filtered group had both a higher number of nodes that were hot (35 vs. 6) and more nodes that were hot and blue (69 vs. 43). In addition, hot secondary level lymph nodes (iliac and deep cervical) were found in 11 of 24 of the basins (46%) in the filtered group compared to 1 of 24 (4%) in the unfiltered group (P <.003). There was no significant difference in injection site or residual basin counts between the two groups, but in vivo counts over the sentinel node sites were significantly lower in the unfiltered group (X = 2670+/-1829 vs. X = 6027+/-4333; P = .003). CONCLUSION: Use of filtered Tc 99 results in more sentinel nodes (both hot/blue and hot non-blue) and a higher proportion of secondary lymph nodes. These findings indicate that the Tc 99 preparation used is a significant variable in the results of lymphatic mapping. It is critical that future clinical studies document which preparation of Tc 99 was used. Only large clinical trials will be able to determine whether the additional nodes found with filtered Tc 99 increase the sensitivity of the technique or merely increase the number of nodes that must be removed unnecessarily.
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