Tox Path Forum*
"Have You Seen This?"
Leukocyte Response Titanium implants were placed within the peritoneal cavities of 10 skeletally mature Sprague-Dawley rats to study the cellular biologic response to titanium. After 28 days the animals were sacrificed and the tissues surrounding the implants were digested and analyzed for titanium by electrothermal atomic absorption spectrophotometry (EAAS). Representative samples of the surrounding tissues were also examined by light microscopy following embedding in methylmethracrylate and staining with heTitanium concentrations matoxylin and eosin (H&E). within the surrounding capsular tissues ranged from 888 to 16,786 ng/g. Light microscopic examination of the H&E sections demonstrated a thin layer of fibrous tissue surrounding the implants with occasional leukocytic infiltrates. However, one animal developed focally severe mixed leukocytic infiltrate adjacent to the implant (Figs. 1 and 2). The titanium concentration in the capsular tissues of this animal was 888 ng/g. An intense histiocytic response to titanium, especially in the presence of wear debris with visible titanium pigments, and capsular tissue concentrations exceeding 50,000 ng/g, has been consistently reported in human tissues associated with total hip replacements (1-3). In tissues without wear debris or visible titanium pigments, published studies report capsular
to Titanium
concentrations of titanium similar to those in our laboratory animal tissues with a minimal leukocytic infiltrate as seen
monsanto.com or
in 9 of 10 animals in
our
study (3, 4).
DANIEL S. JORGENSON Walter Reed Army Institute
of Research D.C. JOSE A. CENTENO Armed Forces Institute of Pathology and Center for Environmental and Toxicologic Pathology, Washington, D. C. MICHAEL H. MAYER Oregon Health Sciences University Washington,
Portland, Oregon MICHAEL J. TOPPER Walter Reed Army Institute of Research Washington, D. C. FLORABEL G. MULLICK Armed Forces Institute of Pathology and Center for Environmental and Toxicologic Pathology, Washington, D. C. PAUL N. MANSON John Hopkins University School of Medicine
Baltimore, Maryland 1.
* Instructions to Authors Readers are invited to submit their own diagnostic challenges or unusual findings or to voice opinions and comments about the current lesion diagnosis or explanation. Cases for the &dquo;Tox Path Forum&dquo; should be sent to the Editorial Office with the following information: 1) species, sex, and age; 2) the nature/class of the test article (if any); 3) brief description and diagnosis; and 4) photographs or data. The information should not exceed two pages (including photographs). Submit both a hard copy and a diskette (Macintosh or PC) indicating version, to expedite rapid review and publication. Submissions will be reviewed for clarity and relevance to the journal readership. Comments and opinions may be sent to the editorial office or by e-mail to knkhan@searle.
Implants
REFERENCES Agins HJ, Alcock NW, Manjula B, et al (1988). Metallic wear in failed titanium-alloy total hip replacements. J. Bone Joint Surg. 70A:
347-356. 2. Dorr LD, Bloeman R, Emmanual BS, and Meldrum R (1990). Histologic, biochemical, and ion analysis of tissues and fluids retrieved during total hip arthroplasty. Clin. Orthop. 261: 82-95. 3. Jorgenson DS, Centeno JA, Mayer MH, Mullick FG, and Manson PN (1996). Analytical evaluation of local tissues surrounding titanium implants. In: Metal Ions in Biology and Medicine, Ph Collery, J Corbella, JL Domingo, JC Etienne, and JM Llobet (eds). John Libby Eurotext, Paris, 4: 583-585. 4. Jorgenson DS, Mayer MH, Ellenbogen RG, et al (in press). Detection of titanium in human tissues after craniofacial surgery. Plast. Re-
[email protected].
constr.
664
Surg.
665
FIG. with a
tissue demonstrating the thin connective tissue layer surrounding 1.-Photomicrograph of H&E-stained large collection of mixed leukocytes (upper left corner), located adjacent to the tissue capsule. X 100.
collection FIG. 2.-Photomicrograph of H&E-stained macrophages, predominate, with mast cells, eosinophils,
of mixed leukocytes found adjacent to a titanium and a few neutrophils seen. No titanium pigments
the
implant (lower right corner),
Mononuclear cells, primaril) visible within the tissues. x 1,000.
implant. are