Willm Uwe Kampen

Mineralization and osteogenesis in the human first rib cartilage

Mineralization and osteogenesis in the human first rib cartilage were studied radiologically and by means of normal and polarized light microscopy. Onset of mineralization occurs at the end of puberty and is located directly beneath the perichondrium. Bone is formed in a typical spur-like pattern, arising medially from the upper edge of the manubrium sterni and laterally from the caudal rim of the bony part of the rib. From the middle of the second decade, large cartilage canals with several blood vessels and loose perivascular connective tissue are seen in central areas of the first costal cartilage. These parts are the last to be mineralized and ossified in old age. The type of osteogenesis cannot be classified according to common patterns. In spite of the subperichondral localization it cannot be intramembranous, because the new bone is separated from the perichondrium by a layer of mineralized cartilage. Osteogenesis cannot be called endochondral compared with the epiphyseal plate for the following reasons: there are no hypertrophied chondrocytes; an immunoreactivity for collagen type X is missing; areas where bone is formed directly on hyaline cartilage could be proved. Vascularization and onset of osteogenesis are separated in time and localization. Mineralization and osteogenesis in human first rib cartilage are physiological age-related changes, which cannot be regarded as degenerative processes. Ossification is not directly correlated with the invasion of blood vessels and cannot be classified as one of the classical concepts of intramembranous or endochondral osteogenesis.

Localization of collagens and alkaline phosphatase activity during mineralization and ossification of human first rib cartilage

The localization of type X collagen and alkaline phosphatase activity was examined in order to gain a better understanding of tissue remodelling during development of human first rib cartilage. First rib cartilages from children and adolescents showed no staining for type X collagen and alkaline phosphatase activity. After onset of mineralization in the late second decade, a peripheral ossification process preceded by mineralized fibrocartilage could be distinguished from a more central one preceded by mineralized hyaline cartilage. No immunostaining for type X collagen was found in either type of cartilage. However, strong staining for alkaline phosphatase activity was detected around chondrocyte-like cells within fibrocartilage adjacent to the peripheral mineralization front, while a weaker staining pattern was observed around chondrocytes of hyaline cartilage near the central mineralization front. In addition, the territorial matrix of some chondrocytes within the hyaline cartilage revealed staining for type I collagen, suggesting that these cells undergo a dedifferentiation process, which leads to a switch from type II to type I collagen synthesis. The study provides evidence that mineralization of the hyaline cartilage areas in human first rib cartilage occurs in the absence of type X collagen synthesis but in the presence of alkaline phosphatase. Thus, mineralization of first rib cartilage seems to follow a different pattern from endochondral ossification in epiphyseal discs.

Imaging of acute heart-transplant rejection using 99m-Technetium labelled oligonucleotides against interleukin-2 mRNA in rats

OBJECTIVES Today, acute cardiac rejection is detected by endomyocardial biopsy, which harbours many risks. Thus, there is a necessity for less invasive methods. Since interleukin-2 (IL2) is over-expressed in acute graft rejection, we use radioactive DNA-fragments complementary to the mRNA of IL2 to detect graft rejection scintigraphically. METHODS In a rat model of acute graft rejection, the oligonucleotide sequence complementary to the mRNA of IL2 is labelled with 99m-Technetium and injected intravenously. Scintigraphic and Geiger-counter activity of the transplants are evaluated and correlated with the current rejection classification of the International Society for Heart and Lung Transplantation (ISHLT). RESULTS From the fourth postoperative day onwards, the scintigraphic images show a significant increase of radioactivity (p<0.05) in the rejected organs than in the accepted grafts. While scintigraphy is not significantly correlated with the standard rejections classification of the ISHLT, there is significant correlation between the ISHLT classification and radioactivity in the Geiger-counter analysis. CONCLUSIONS Radioactively labelled anti-sense-oligonucleotides against mRNA of IL2 may be a promising approach for the detection of acute transplant rejection in vivo.

Limited sensitivity of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl ] benzamide whole-body scintigraphy in patients with malignant melanoma: a comparison with thallium-201 imaging.

Abstract. The aim of this prospective study was to assess the diagnostic value of iodine-123-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide (IBZM) whole-body imaging in comparison to thallium-201 scintigraphy in patients with metastatic malignant melanoma. Ten patients with suspected or proven locoregional metastases of malignant melanoma underwent whole-body scintigraphy both with 201Tl and 123I-IBZM prior to scheduled surgery. Whole-body scans and planar scintigrams were acquired at 5 min and 30 min after injection of 100 MBq 201Tl and at 10 min, 2 h, 4 h and 24 h after injection of 185 MBq 123I-IBZM. Ten out of 12 melanoma metastases, both melanotic and amelanotic as proven histologically, were detected by 201Tl with a sensitivity of 83%. 123I-IBZM showed tracer uptake only in 3 melanotic metastases (sensitivity: 25%) with a maximum tumor-to-background ratio within 4 h, while none of the amelanotic metastases was IBZM-positive. All lesions localized by 123I-IBZM showed tracer uptake of 201Tl as well, while 201Tl-negative lesions were also negative with IBZM. Because of the poor results of IBZM, the study was terminated after an interim evaluation of 10 patients. 123I-IBZM is a tracer with only moderate sensitivity in melanotic melanoma lesions, suggesting that this method has no clinical value as a routine investigation in melanoma patients. In comparison, our previous results with 201Tl whole-body scintigraphy yielded a significantly higher sensitivity of about 80% in patients with locoregional melanoma metastases and may thus offer considerable potential in non-PET melanoma imaging.

Myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186rhenium-(tin)1,1- hydroxyethylidene diphosphonate (186Re-HEDP).

The aim of this study is to investigate the myeloprotective effects of different amifostine regimens in rabbits undergoing high-dose treatment with 186Rhenium-(tin)1,1-hydroxyethylidene diphosphonate (186Re-HEDP) and to analyze the impact of amifostine on the bone uptake of the radiopharmaceutical. All animals were treated with 1000 MBq 186Re-HEDP. Group ReA received 500 mg amifostine prior to radionuclide therapy, group ReA3 received 3 x 200 mg amifostine 24 hours and 30 minutes prior to and 24 hours after radionuclide therapy. Group ReC served as control receiving no amifostine. Scintigrams were acquired to quantify the skeletal uptake of 186Re-HEDP, and platelet and leucocyte counts were measured. The mean decrease in platelets was 36% +/- 2%, 37% +/- 3%, and 61% +/- 5% for ReA, ReA3, and ReC, respectively. The decrease in ReC was significantly higher than in amifostine-treated animals with no difference between ReA and ReA3. For the leucocytes the mean decrease was 75% +/- 12%, 82% +/- 5%, and 73% +/- 4%, with no significant differences between the respective groups. Bone uptake of 186Re-HEDP was significantly reduced by 50% in ReA and ReA3 compared to ReC. Thus, the 3-day amifostine regimen had no advantage over the single dose regimen, with both regimens reducing bone uptake and yielding a platelet-protective but no leucoprotective effect.

Schmerztherapie von Skelettmetastasen mittels ionisierender Strahlung

Die perkutane Strahlentherapie ist eine wirksame Masnahme zur Reduktion der lokalen inflammatorischen Reaktion sowie zur Inaktivierung proliferativer Eigenschaften des Tumors. Daher verfugt sie uber eine messbare Effektivitat bei Schmerzen, die durch Knochenmetastasen hervorgerufen werden (Adamietz u. Diel 2003, Arcangeli et al. 1998, Blum et al. 2003).

LOCALIZATION OF TYPE I AND II COLLAGEN DURING DEVELOPMENT OF HUMAN FIRST RIB CARTILAGE

The localization of fibrillar type I and II collagen was investigated by immunofluorescence staining with specific antibodies in order to obtain a better understanding of tissue remodelling during the development of first rib cartilage. In childhood and early adolescence type I collagen was found to be restricted to the perichondrium of first rib cartilage, while type II collagen was localized in the matrix of hyaline cartilage. However, in advanced age type I collagen was also found in the territorial matrix of intermediate and central chondrocytes of first rib cartilage. The matrix of subperichondrial chondrocytes was negative for type I collagen. This suggests that some chondrocytes in first rib cartilage undergo a modulation to type I collagen-producing cells. The first bone formation was observed in rib cartilages of 20- to 25-year-old adults. Interestingly, the ossification began peripherally, adjacent to the innermost layer of the perichondrium where areas of fibrocartilage had developed. The newly formed bone matrix showed strong immunostaining for type I collagen. Fibrocartilage bordering peripherally on bone matrix revealed only a faint staining for type I collagen, but strong immunoreactivity to type II collagen. The interterritorial matrix of the central chondrocytes failed to react with the type II collagen antibody, in both men and women, from the end of the second decade. These observations indicate that major matrix changes occur at the same time in male and female first rib cartilages. Thus, our findings indicate that ossification in human first rib cartilage does not follow the same pattern as that observed in endochondral ossification of epiphyseal discs or sternal cartilage.

QM und Zertifizierung – eine Möglichkeit zur Verbesserung der Qualität in der Praxis?

This paper describes several general conditions, the content, both advantages and disadvantages as well as the realisation of a Quality Management System in a nuclear medicine practice. The aim is to facilitate the implementation and a naturally handling of QM in daily routine work. Such a system must be charged with content to assure both its reasonable application and continuous improvement; thus, several examples from daily practice are given. Single procedures of quality assurance are described as well as the handling of mistakes and complaints. Finally, advantages and disadvantages of an official certification in QM are discussed.