The role of nuclear medicine in oncology

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the “tumor-specific” radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 cloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatine-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.     

Recombinant human stem cell factor stimulates growth of a human glioblastoma cell line expressing c-kit protooncogene.

The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications.     

DIALLELIC POLYMORPHISM MAY EXPLAIN VARIATIONS OF THE BLOOD CONCENTRATION OF MANNAN-BINDING PROTEIN IN ESKIMOS,BUT NOT IN BLACK AFRICANS

Mannan-binding protein (MBP) is a lectin which, upon binding to certain carbohydrates, activates the classical pathway of complement without the involvement of antibody or C1q. Deficiency of the MBP is associated with an opsonic defect and recurrent infections during early life. An amino acid substitution in the exon 1 at codon 54 in the MBP gene (GGC [glycine] to GAC [aspartic acid]) has been shown to be closely associated with low MBP concentration in Caucasoids. The gene frequency of the mutant allele in this population has been estimated at 0.13. In the study described here, we investigated the association between the mutant allele and MBP protein concentration in Eskimos from East-Greenland and black Africans from the Baringo District in Kenya. The frequency of the GAC allele was identical in Eskimos and Caucasoids (0.13). No overlap with regard to MBP concentration between the genotypes was found in the Eskimos. In contrast, the Africans revealed a low frequency of the GAC allele (0.009). However, the median MBP protein concentration was approximately 5 times lower among the Africans than the Eskimos. In 12.6% of the Africans and in 2.5% of the Eskimos, MBP was undetectable. Thus, MBP deficiency is the most frequent immunodeficiency so far described. The high prevalence of MBP deficiency among healthy individuals indicates that MBP deficiency also confers some selective advantages. We advance the hypothesis that MBP deficiency is maintained in populations because MBP deficiency decreases the infectivity of some intracellular micro-organisms which are dependent on opsonization.     

Recurrent locking of knee joint caused by intraarticular migration of bioabsorbable tibial interference screw after arthroscopic ACL reconstruction

Two cases are reported in which, after ACL reconstruction with autologous hamstring grafts, tibial polylactide interference screws migrated into the knee joint. Clinically, both patients presented with recurrent locking of the joint. In one case, a broken 15 mm-long tip of the screw was found intra-articularly. In the other case, the whole screw had migrated into the joint cavity. The degradation process of polylactic acid, operative technique and bone quality are discussed as possible reasons for these complications.     

Die Intensivierung der gerichtlichen Kontrolle des Einheitlichen Bewertungsmaßstabs und das Ende der Praxisbudgets

Ohne Zusammenfassung     

Kammerflimmern bei einem 27-j?hrigen Patienten mit Contusio cordis

Zusammenfassung Hintergrund: Bei Patienten mit stumpfem Thoraxtrauma muss mit einer Contusio cordis gerechnet werden. Das Spektrum der Symptomatik variiert von einer leichten regionalen myokardialen Funktionsstörung bis hin zur Ruptur und zum plötzlichen Herztod. Fallbeschreibung: Ein 27-jähriger Patient wurde nach einem Fußtritt gegen die Brust bei Kammerflimmern reanimiert. Das EKG sowie das Enzymmuster entsprachen denen eines akuten Myokardinfarkts, echokardiographisch zeigte sich eine Hypokinesie apikal und anteroseptal bei mittelgradig reduzierter Pumpfuktion. Die 10 Tage nach dem Trauma durchgeführte Koronarangiographie und Lävokardiographie ergaben einen unauffälligen Befund. Schlussfolgerung: Als Ursache des primären Kammerflimmerns und der initialen elektro- und echokardiographischen Befunde muss aufgrund der Anamnese eine Contusio cordis diskutiert und in der Therapie berücksichtigt werden. Abstract Background: Patients with a blunt chest trauma often sustain myocardial contusion. The spectrum of symptoms varies from regional myocardial dysfunction to myocardial rupture of sudden cardiac death. Case Report: After a kick against his chest, a 27-year-old patient was resuscitated because of ventricular fibrillation. ECG and enzymatic pattern corresponded to an acute myocardial infarction, the echocardiogram revealed an apical and anteroseptal hypokinesia. 10 days after the acute event, coronary arteriography and ventriculography did not show any abnormalities. Conclusion: On the basis of the anamnesis, a myocardial contusion must be discussed as reason for the ventricular fibrillation and the pathologic findings in ECG and echocardiogram. This has to be considered in the therapy.     

An Assay for Mannan-Binding Lectin-Associated Serine Protease 3, MASP-3

In analogy to DNA microarrays, protein microarrays offer a new distinct possibility to perform sensitive high-throughput global proteome analysis. However, the development of the protein microarray technology will place high demands upon the design of both probes and solid supports. The analysis of thousands of heterogeneous proteins on a single microarray requires the use of uniform probes, such as antibodies, directly designed for protein microarray applications. We have recently generated a human recombinant single-chain Fv antibody library, genetically constructed around one framework, the nCoDeR-library, containing 2 × 1010 clones. Single framework antibody fragments (sinFabs) selected from this library were successfully applied as probes for microarrays providing sensitive detection in the 600 attomol (mass spectrometry) and the 300 zeptomole range (fluorescence). However, the choice of framework is critical. We have shown that the selected nCoDeR framework displayed excellent functional on-chip stability and arrayed dehydrated probes retained their activity for several months. Furthermore, we have addressed the issues of biocompatibility of the solid support and immobilization strategies for our microarray setup. An in-house-designed substrate, macroporous silicon coated with nitrocellulose (MAP3-NC7), displayed properties equal to, or better than, those of five commercially available supports used as reference surfaces. We have also evaluated different coupling strategies, such as adsorption, covalent coupling, diffusion and affinity coupling. Using a novel affinity tag, the double-(his)6-tag, we increased the binding efficiency of sinFab-molecules to Ni2⁺-coated solid supports, thereby allowing nonpurified probes to be directly applied.     

DSA—Control of implanted devices for arterial hepatic perfusion

In contrast to conventional film angiography, the perfusion pattern of hepatic arterial chemotherapy was consistently visualized by DSA in 40 patients with implanted Infusaid pump or Port-A devices. Incomplete perfusion of a liver region by the cytotoxic agent was recognized by DSA as accurately as by nuclide scintigraphy. Furthermore, DSA appeared to be more sensitive in determining aberrantly perfused extrahepatic regions; this was especially true when there was a nonligated right hepatic artery. Specific details of vascular lesions and associated complicating events also could be satisfactorily analyzed by DSA only.