Kuldeep K. Bhargava

UNLABELLED: The objectives of this study were to investigate (18)F-FDG imaging, using a coincidence detection system, for diagnosing prosthetic joint infection and to compare it with combined (111)In-labeled leukocyte/(99m)Tc-sulfur colloid marrow imaging in patients with failed lower extremity joint replacements. METHODS: Fifty-nine patients--with painful, failed, lower extremity joint prostheses, 40 hip and 19 knee--who underwent (18)F-FDG, labeled leukocyte, and bone marrow imaging, and had histopathologic and microbiologic confirmation of the final diagnosis, formed the basis of this investigation. (18)F-FDG images were interpreted as positive for infection using 4 different criteria: criterion 1: any periprosthetic activity, regardless of location or intensity; criterion 2: periprosthetic activity on the (18)F-FDG image, without corresponding activity on the marrow image; criterion 3: only bone-prosthesis interface activity, regardless of intensity; criterion 4: semiquantitative analysis--a lesion-to-background ratio was generated, and the cutoff value yielding the highest accuracy for determining the presence of infection was determined. Labeled leukocyte/marrow images were interpreted as positive for infection when periprosthetic activity was present on the labeled leukocyte image without corresponding activity on the marrow image. RESULTS: Twenty-five (42%) prostheses, 14 hip and 11 knee, were infected. The sensitivity, specificity, and accuracy of (18)F-FDG, by criterion, were as follows: criterion 1: 100%, 9%, 47%; criterion 2: 96%, 35%, 61%; criterion 3: 52%, 44%, 47%; criterion 4: 36%, 97%, 71%. The sensitivity, specificity, and accuracy of labeled leukocyte/marrow imaging were 100%, 91%, and 95%, respectively. WBC/marrow imaging, which was more accurate than any of the (18)F-FDG criteria for all prostheses, as well as for hips and knees separately, was significantly more sensitive than criterion 3 (P < 0.001) and criterion 4 (P < 0.001) and was significantly more specific than criterion 1 (P < 0.001), criterion 2 (P < 0.001), and criterion 3 (P < 0.001). CONCLUSION: Regardless of how the images are interpreted, coincidence detection-based (18)F-FDG imaging is less accurate than, and cannot replace, labeled leukocyte/marrow imaging for diagnosing infection of the failed prosthetic joint.

To examine the distribution of intrasplenically transplanted hepatocytes, we used HBsAg-producing G7 HBV transgenic hepatocytes or cells labeled with 111In. Most hepatocytes translocated to the liver (55% +/- 7%; mean +/- S.D.); the spleen retained a smaller fraction (15% +/- 3%); and some transplanted cells localized in lungs (3%) or pancreas (1%). Transplanted hepatocytes were rapidly assimilated into the liver lobule. Morphometrical quantitation indicated that the numbers of transplanted hepatocytes in the liver at 48 hr and at 9 mo after transplantation were similar. Serum HBsAg was detected in recipients of the G7 HBV hepatocytes during the 1-yr experiment. These results indicate that a large number of hepatocytes can be reproducibly delivered to the liver by transplantation into the spleen. Transplanted hepatocytes engraft rapidly, assimilate into host liver, maintain normal function and survive permanently. Systems for safe delivery and localization of hepatocytes in the liver represent a critical step toward successfully accomplishing hepatocyte-directed gene therapy and repopulation of the acutely devastated liver.

After transplantation, hepatocytes entering liver sinusoids are engrafted, whereas cells entrapped in portal spaces are cleared. We studied whether hepatic sinusoidal dilatation will increase the entry of transplanted cells in the liver lobule, improve cell engraftment, and decrease microcirculatory perturbations. F344 rat hepatocytes were transplanted intrasplenically into syngeneic dipeptidyl peptidase IV (DPPIV)-deficient rats. Animals were treated with adrenergic receptor blockers (phentolamine, labetalol), a calcium channel blocker (nifedipine), and splanchnic vasodilators (nitroglycerine, calcitonin gene-related peptide [CGRP], glucagon). Transplanted cells were localized by histochemistry. The hepatic microcirculation was studied with in vivo videomicroscopy. Changes in cell translocations were analyzed by injection of (99m)Tc-labeled hepatocytes. Pretreatment with phentolamine and nitroglycerine increased transplanted cell entry in liver sinusoids, whereas labetalol, nifedipine, CGRP, and glucagon were ineffective. Increased deposition of transplanted cells in sinusoids resulted in greater cell engraftment. In vivo microscopy showed disruption of sinusoidal blood flow immediately after cell transplantation with circulatory restoration requiring more than 12 to 24 hours after cell transplantation. However, in nitroglycerine-treated animals, sinusoidal blood flow was perturbed less. Nitroglycerine did not meaningfully increase intrapulmonary cell translocations. In conclusion, these findings indicate that hepatic sinusoidal capacitance is regulated by alpha-adrenergic- and nitroglycerine-responsive elements. Sinusoidal vasodilatation benefited intrahepatic distribution of transplanted cells and restored hepatic microcirculation after cell transplantation. This shall facilitate optimization of clinical cell transplantation and offers novel ways to investigate vascular mechanisms regulating hepatic sinusoidal reactivity.