[Current oncologic concepts and emerging techniques for imaging of head and neck squamous cell cancer]. / Aktuelle Standards und Fortschritte in der onkologischen Bildgebung von Kopf-Hals-Tumoren.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing and currently they account for 5% of all malignancies worldwide. Inspite of ongoing developments in diagnostic imaging and new therapeutic facilities, HNSCC still represents a multidisciplinary challenge. One of the most important prognostic factors in HNSCC is the presence of lymph node metastases. Patients with confirmed nodal involvement have a considerable reduction of their 5-year overall survival rate. In the era of individually optimised surgery, chemotherapy and intensity modulated radiotherapy, the main role of pre- and posttherapeutic imaging remains cancer detection at an early stage and accurate follow-up. The combined effort of early diagnosis and close patient monitoring after surgery and/or radio-chemotherapy influences disease progression and outcome prediction in patients with HNSCC. This review article focuses on currrent oncologic concepts and emerging tools in imaging of head and neck squamous cell cancer. Besides the diagnostic spectrum of the individual imaging modalities, their limitations are also discussed. One main part of this article is dedicated to PET-CT which combines functional and morphological imaging. Furthermore latest developments in MRT are presented with regard to lymph node staging and response prediction. Last but not least, a clinical contribution in this review explains, which information the head and neck surgeon requires from the multimodality imaging and its impact on operation planning.

[Complications of venous port systems : Radiological diagnostics and minimally invasive therapy]. / Komplikationen venöser Portsysteme : Radiologische Diagnostik und minimalinvasive Therapie.

INTRODUCTION: Documentation of a correct port placement is a routine investigation in radiology. This article describes typical complications of port catheters and minimally invasive treatment options which can guarantee further use without complications. MATERIAL AND METHODS: From January 2009 to May 2010 a surgical port placement was carried out on 174 patients at the University Clinic in Mannheim and of these, 52 patients were admitted to our institute for radiological imaging of the port. Minimally invasive treatment options are presented based on the observed port complications. RESULTS: Of the 52 patients 7 (13.5%) received a port catheter lysis. A successful port position correction was carried out in 3 (5.8%) patients with a malpositioned port catheter and port removal was recommended in 2 patients (3.8%) due to extensive arm venous thrombosis. A minimally invasive port catheter treatment allowed further use of the port system without operative revision in the corresponding patients. The measures were tolerated very well by the patients without postinterventional complications.

Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets.

We purified poly(A)+ mRNA from the spleen and lymph nodes at designated times after infection with Leishmania major in genetically susceptible BALB/c and resistant C57BL/6 mice. The steady-state levels of IL-2, IFN-gamma, IL-4, and IL-1 beta mRNA were determined using Northern hybridizations. IL-2 mRNA levels in the infected organs of BALB/c and C57BL/6 mice were comparable after infection, but IFN-gamma and IL-4 mRNA levels were reciprocally expressed. Levels of IFN-gamma mRNA in C57BL/6 draining nodes and spleen were significantly greater than in BALB/c mice except at 4 and 6 wk of infection, when splenic IFN-gamma mRNA levels were transiently comparable. In contrast, IL-4 mRNA was apparent only in BALB/c and not in C57BL/6 nodes and spleen. Tissue levels of IL-1 beta mRNA were 10-20-fold greater in BALB/c mice. BALB/c mice were pretreated with GK1.5 mAb, a manipulation that promotes healing of subsequent infection by transiently depleting L3T4+ cells. At 8 wk of infection, by which time lymphoid organs were repopulated with L3T4+ cells, GK1.5-pretreated BALB/c mice produced IFN-gamma, but not IL-4 message. Serum levels of IgE were markedly elevated in infected BALB/c, but not in infected C57BL/6 or GK1.5-pretreated BALB/c mice, consistent with in vivo biologic activity of IL-4 in nonhealing mice. Treatment of infected BALB/c mice with neutralizing anti-IL-4 antibody abolished the elevation of serum IgE and significantly attenuated the progression of disease as assessed by size and ulceration of the lesion, and by reduction in the number of tissue parasites. Both protective and deleterious responses to Leishmania infection have previously been shown to be L3T4+ cell dependent. Our findings are consistent with the differential expansion of protective, IFN-gamma-producing Th1 cells in healing mice, and the expansion of deleterious, IL-4-producing Th2 cells in nonhealing mice. The inverse relationship of IFN-gamma and IL-4 gene expression during leishmaniasis may underlie the divergence of cellular and humoral immunity that occurs during chronic infection with Leishmania and possibly other intracellular parasites.

Cure of murine leishmaniasis with anti-interleukin 4 monoclonal antibody. Evidence for a T cell-dependent, interferon gamma-independent mechanism.

BALB/c mice infected with Leishmania major develop fatal, progressive disease, despite an immune response characterized by expansion of CD4+ T cells in the draining lymph nodes. The immune response has been further characterized by a lack of IFN-gamma mRNA, but increased IL-4 mRNA in lymphoid tissues, and striking elevation of serum IgE. Treatment of infected BALB/c mice with rIFN-gamma at doses shown to be beneficial in other protozoan infections was insufficient to ameliorate L. major infection. In contrast, neutralization of IL-4 by six weekly injections of mAb 11B11 led to attenuation of disease in 100% of animals, and complete cure in 85%. Resolution of disease required the presence of T cells, and recovered mice remained resistant to reinfection at 12 wk. This immunity was adoptively transferable and was dependent on both CD4+ and CD8+ cells. Although administration of anti-IL-4 was associated with fourfold increase in IFN-gamma mRNA in lymph node cells draining the lesion, the coadministration of neutralizing R4 6A2 anti-IFN-gamma mAb had no effect on resistance to disease. This was in marked contrast to resolution of disease in both resistant C57BL/6- and GK1.5-pretreated BALB/c mice that was abrogated by in vivo treatment with anti-IFN-gamma. These data suggest a novel mechanism of cellular immunity established by interference with the development of Th2 cells during infection.

Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells.

To understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.

Release of interleukin 1 inhibitory activity (contra-IL-1) by human monocyte-derived macrophages infected with human immunodeficiency virus in vitro and in vivo.

Infection of monocyte-macrophages with human immunodeficiency virus may be central to the pathogenesis of the acquired immunodeficiency syndrome. The ability of infected macrophages to prime T cells through IL-1 production was investigated in vitro. Purified human monocytes maintained in suspension culture were infected with strain HIV-DV. Intracellular expression of virus p24 antigen increased from undetectable levels immediately after infection to 13-59% of cells by 10-14 d; infected macrophages remained viable for up to 60 d. Supernatants collected between 14 and 20 d after infection were examined in the murine thymocyte co-mitogenesis assay and demonstrated to contain a potent IL-1 inhibitor, designated contra-IL-1. Contra-IL-1 activity was present in all supernatants examined after 4 d of infection, and peaked coincident with peak p24 antigen expression. Inhibitory activity was not present in uninfected cells. Contra-IL-1 activity eluted after gel filtration with an approximate molecular weight of 9 kD. Inhibitory activity was removed by exposure to heat or acid pH, or by incubation with chymotrypsin or staphylococcal V8 protease. Contra-IL-1 did not inhibit IL-2- or IL-4-dependent proliferation of murine T cell lines. Despite its ability to inhibit IL-1 activity, contra-IL-1 did not interfere with the binding of recombinant IL-1 beta to a fibroblast cell line. Contra-IL-1 inhibited the proliferation of normal peripheral blood mononuclear cells to both concanavalin A and tetanus toxoid; inhibition could be attenuated by the addition of exogenous IL-1. Messenger RNA extracted from infected macrophages was examined by Northern analysis for the presence of message to IL-1 beta. No message was apparent, suggesting that the presence of contra-IL-1 was not obscuring the concomitant release of IL-1. Infected macrophages stimulated with endotoxin generated readily detectable message for IL-1 beta. Spleen macrophages purified from two patients with AIDS complicated by immune thrombocytopenia spontaneously expressed p24 antigen in vitro and released contra-IL-1 activity into the media. Contra-IL-1 may contribute to the immune dysfunction of AIDS.

[MDCT after balloon kyphoplasty: analysis of vertebral body architecture one year after treatment of osteoporotic fractures]. / MDCT nach Ballonkyphoplastie: Analyse der Wirbelkörperarchitektur 1 Jahr nach Behandlung osteoporotischer Sinterungsfrakturen.

PURPOSE: To evaluate the value of MDCT in the monitoring of vertebral body architecture after balloon kyphoplasty and observe morphological changes of the vertebral body. MATERIAL AND METHODS: During a period of 26 months, 66 osteoporotic fractures of the vertebral bodies were treated with percutanous balloon kyphoplasty. The height of the vertebral body, width of spinal space, sagittal indices, kyphosis und COBB angle, and cement leakage were evaluated by computed tomography before and after treatment and in a long-term follow up. Statistical analysis was performed by calculating quantitative constant parameters of descriptive key data. In addition, parametric and distribution-free procedures were performed for all questions. RESULTS: After kyphoplasty, the treated vertebral bodies showed a significant gain in the height of the leading edge (0.15 cm; p < 0.0001) and in the central part of the vertebral body (0.17 cm; p < 0.0001). The height of the trailing edge did not change significantly. A corresponding gain in the sagittal index was found. The index remained stable during follow-up. Treated vertebral bodies as well as untreated references showed a comparable loss of height over the period of one year. The shape of the vertebral bodies remained stable. In comparison to these findings, treated vertebral bodies showed a reduced loss of height. A significant change in kyphosis und the COBB angle was noted. In total, pallacos leakage was detected in 71 % of cases. CONCLUSION: MDCT is an accurate method for evaluating vertebral body architecture after treatment with balloon kyphoplasty. Morphological changes in the vertebral bodies, and complications such as pallacos leakage and progression of osteoprosis can be accurately documented. The significant increase in the vertebral body height after treatment is closely correlated with a gain in the sagittal index and reduced kyphosis and COBB angle.

[Whole-body MSCT of patients after polytrauma: abdominal injuries]. / Ganzkörper-MSCT beim Polytrauma: Abdominelle Verletzungen.

PURPOSE: The goal of this retrospective study was to evaluate the spectrum of abdominal injuries and the reliability of computed tomography-based diagnosis in patients after polytrauma. MATERIAL AND METHODS: CT findings and clinical reports for 177 patients after polytrauma were evaluated with regard to abdominal injuries. Clinical patient reports at the time of discharge from the hospital were utilized as the standard of reference. Abdominal injuries resulting from an accident, frequent additional traumas and following therapeutic procedures were recorded. In the case of discrepancies in the reports, the CT scans were viewed retrospectively. RESULTS: In 30 out of 177 patients, 42 abdominal injuries were detected. 69 % of the injuries were caused by traffic accidents while 31 % resulted from falls. Liver and spleen injuries were the most common. 50 % of the cases were treated surgically, and the other half of the cases underwent non-surgical conservative therapy. Massive chest traumas, pelvic injuries, cerebral traumas and injuries to extremities were commonly associated with abdominal injuries. Evaluation of the discrepancies in the clinical reports showed that injury to the pancreas and the small intestine were not successfully detected on CT, thus resulting in a false negative diagnosis. Early stages of organ parenchyma laceration were also initially misdiagnosed on CT. CONCLUSION: Contrast-enhanced whole-body MSCT is a reliable and rapid method for diagnosing abdominal injuries in patients after polytrauma. Only very few patterns of injury are not detected on CT. The appearance of fluid collection in the abdomen is an indicator of possible parenchyma injury and requires further evaluation in cases of clinically suspected organ trauma.

[Localization of bleeding using 4-row detector-CT in patients with clinical signs of acute gastrointestinal hemorrhage]. / Blutungslokalisation mittels 4-Zeilen-Spiral-CT bei Patienten mit klinischen Zeichen einer akuten gastrointestinalen Hämorrhagie.

PURPOSE: There is no gold-standard regarding the diagnostic work-up and therapy of an acute gastrointestinal (GI) hemorrhage. In most cases endoscopy provides the diagnosis but in a low percentage this modality is not feasible or negative. Purpose of this study was to evaluate the role of multi-phase Multi-Slice-Computertomography (MSCT) as a modality to diagnose and locate the site of acute GI hemorrhage in case of unfeasible or technically difficult endoscopy. MATERIALS AND METHODS: 58 patients, presenting with clinical signs of lower GI hemorrhage, were examined through a 24-month period. Preliminary endoscopy was either negative or unfeasible. Images were obtained with a four-detector row CT with an arterial (4 x 1 mm collimation, 0.8 mm increment, 1.25 mm slice width, 120 kV, 165 mAs) and portal venous series (4 x 2,5 mm collimation, 2 mm increment, 3 mm slice width, 120 kV, 165 mAs). Time interval between endoscopy and CT varied between 30 minutes and 3 hours. The results of the MSCT were correlated with clinical course and surgical or endoscopical treatment. RESULTS: 20 of the 58 patients (34 %) undergoing MSCT had a bleeding site identified, thus providing decisive information for the following intervention. In case of a following therapeutic intervention there was 100 % correlation regarding the bleeding site. In 38 of the 58 patients (66 %), a bleeding site was not identified by MSCT. Twenty of these 38 patients (53 %) were stable and required no further treatment. In 18 of these 38 patients further interventional therapy was required due to continuing hemorrhage and in all of those patients the bleeding site was detected by intervention. CONCLUSION: Compared to other diagnostic methods MSCT is a fast, widely-available and low-risk technique for the localization of active GI hemorrhage. The clinical use seems to be justified since in more than one third of the patients, MSCT demonstrates the site of bleeding and provides decisive information for further interventional therapy. Concerning those patients, in whom MSCT is negative (38 out of 58 patients), only every second patient requires any additional diagnostic work-up.

Binding protein-3-selective insulin-like growth factor I variants: engineering, biodistributions, and clearance.

Insulin-like growth factor I (IGF-I) is a potent anabolic peptide that mediates most of its pleiotropic effects through association with the IGF type I receptor. Biological availability and plasma half-life of IGF-I are modulated by soluble binding proteins (IGFBPs), which sequester free IGF-I into high affinity complexes. Elevated levels of specific IGFBPs have been observed in several pathological conditions, resulting in inhibition of IGF-I activity. Administration of IGF-I variants that are unable to bind to the up-regulated IGFBP species could potentially counteract this effect. We engineered two IGFBP-selective variants that demonstrated 700- and 80,000-fold apparent reductions in affinity for IGFBP-1 while preserving low nanomolar affinity for IGFBP-3, the major carrier of IGF-I in plasma. Both variants displayed wild-type-like potency in cellular receptor kinase assays, stimulated human cartilage matrix synthesis, and retained their ability to associate with the acid-labile subunit in complex with IGFBP-3. Furthermore, pharmacokinetic parameters and tissue distribution of the IGF-I variants in rats differed from those of wild-type IGF-I as a function of their IGFBP affinities. These IGF-I variants may potentially be useful for treating disease conditions associated with up-regulated IGFBP-1 levels, such as chronic or acute renal and hepatic failure or uncontrolled diabetes. More generally, these results suggest that the complex biology of IGF-I may be clarified through in vivo studies of IGFBP-selective variants.

Evaluation of breath-hold contrast-enhanced 3D magnetic resonance angiography technique for imaging visceral abdominal arteries and veins.

RATIONALE AND OBJECTIVES: To evaluate the diagnostic value of breath-hold contrast-enhanced 3D magnetic resonance angiography (MRA) for assessment of the visceral abdominal arteries and veins in patients with suspected abdominal neoplasms. METHODS: Twenty-one patients underwent MR imaging on a 1.5 T unit using a body phased-array coil. MRA was performed with a 3D-FLASH sequence (TR 3.8 ms, TE 1.3 ms, flip angle 25 degrees, acquisition time 20 seconds), 8 to 12 seconds after an intravenous bolus injection of Gd-DTPA. The acquisition delay between the arterial and the portal venous phase was 12 seconds. The image quality and the degree of vascular involvement were evaluated using coronal source images and maximum intensity projection reconstructions. Diagnosis was confirmed by surgery/histology. RESULTS: Image quality was optimal in more than 85% of the patients (19/21 arterial phase and 17/21 portal venous phase). MRA correctly predicted vascular status in 20 of 21 patients (95%), with complete concordance between MRA results and surgical findings. In one patient with chronic pancreatitis, MRA demonstrated a false-positive finding that could not be confirmed surgically. CONCLUSIONS. Breath-hold contrast-enhanced 3D-MRA is a valuable technique for assessing visceral abdominal arteries and veins.

[Bolus tracking and NaCl bolus in biphasic spiral CT of the abdomen]. / Bolustriggerung und NaCl-Bolus bei der biphasischen Spiral-CT des Abdomens.

PURPOSE: To optimise injection parameters in helical CT of the abdomen with individual bolus tracking and subsequent NaCl bolus injection. To investigate the effect of bolus tracking on image quality in the abdomen. METHODS: Patients were randomised into three examination protocols and underwent biphasic helical CT (Hi-Speed Advantage, GE). The effect of NaCl bolus on duration of aortic enhancement was investigated. Contrast enhancement in parenchyma and vessels was examined. The influence of body mass index, injection flow and contrast material volume on enhancement was evaluated. RESULTS: Subsequent injection of NaCl provided significant extension of contrast enhancement in the aorta. Optimal image quality for pancreas and abdominal arteries was achieved in the arterial phase and for liver, spleen, kidneys and abdominal veins in the portal venous phase. Body mass index, injection flow and contrast material volume showed a significant influence on the time intervals resulting from bolus tracking. CONCLUSION: Individual bolus tracking with subsequent injection of 20 ml NaCl bolus optimises intravenous contrast application.

Kinase receptor activation (KIRA): a rapid and accurate alternative to end-point bioassays.

We have developed a novel strategy for a rapid bioassay that is accurate, precise, sensitive, and high capacity. It is capable of quantifying ligand bioactivity by measuring ligand-induced receptor tyrosine kinase activation in terms of receptor phosphorylation. The assay, termed a 'kinase receptor activation' or KIRA, utilizes two separate microtiter plates, one for ligand stimulation of intact cells, and the other for receptor capture and phosphotyrosine ELISA. The assay makes use of either endogenously expressed receptors or stably transfected receptors with a polypeptide flag. KIRA assays for the ligands IGF-I and NGF were compared to their corresponding endpoint bioassays (3T3 cell proliferation for IGF-I and PC12 cell survival for NGF). The KIRA assays showed excellent correlation with the more classical endpoint bioassays. Further, they were highly reproducible, minimizing the requirement for repeat assays. The KIRA assay format has great potential as a rapid, accurate and precise bioassay, both for potency determination as well as stability-indicating analyses.

Antibody binding regions on human nerve growth factor identified by homolog- and alanine-scanning mutagenesis.

The binding specificities of a panel of mouse monoclonal antibodies (MAbs) to human nerve growth factor (hNGF) were determined by epitope mapping using chimeric and point mutants of NGF. Subsequently, the MAbs were used to probe NGF structure-function relationships. Six MAbs, which recognize distinct or partially overlapping regions of hNGF, were evaluated for their ability to block the binding of hNGF to the TrkA and p75 NGF receptors in various in vitro assays, which included blocking of TrkA autophosphorylation and blocking of NGF-dependent survival of dorsal root ganglion sensory neurons. Three MAbs (911,912,938) were potent blockers of all activities. Potent blocking of p75 binding occurs only with MAb 909, which recognizes an NGF region identified by mutagenesis as important for NGF-p75 binding. These results are consistent with recently proposed models of binding regions involved in NGF-TrkA and NGF-p75 interactions generated through mutagenic analysis and structure determination of the NGF-TrkA complex. These studies provide insight to the epitope specificities and potency of MAbs that would be useful for physiological NGF blocking studies.

[Results of balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures]. / Ergebnisse der Ballonkyphoplastie in der Behandlung von osteoporotischen Wirbelkörperfrakturen.

The aim of this study was to evaluate the reduction of pain, improvement of sagittal alignment, complications and intermediate term results of balloon kyphoplasty in the treatment of osteoporotic vertebral compression fractures (VCF). The study group consisted of 87 patients with 145 VCFs which were not responsive to non-operative treatment. All data were collected prospectively. Improvement of sagittal alignment (Cobb and kyphotic angles, anterior, middle and posterior height) was determined from CT scans. Pain was evaluated by means of a visual analogue scale (VAS). Postoperative CT scans revealed a significant reduction of the mean kyphotic angle of 5.7 degrees (range 2-24 degrees ) and a significant reduction of pain from 7.8+/-2.4 to 2.0+/-1.5 in the VAS (improvement of pain in 95.5% of patients). An asymptomatic leakage of cement was observed in 28 out of 145 vertebrae (19.3%). The outcome of 35 patients with 51 VCFs was evaluated after a mean of 13 (range 12-70) months (CT and VAS) and there was a persisting reduction of pain and no loss of reduction. In this group of patients new symptomatic fractures were evident in 4 and clinically asymptomatic (only seen on CT) fractures were detected in 5 out of 35 patients, 7 fractures were adjacent to and 2 fractures were remote from the initially treated level. In two patients an asymptomatic moderate loss of reduction was detected. These intermediate term results indicate that kyphoplasty reduces pain and improves sagittal alignment in patients with VCF. However, in 26% of patients new fractures occurred, predominantly in adjacent levels but approximately 50% of these fractures were clinically asymptomatic.

Plasma creatinine determination in mice and rats: an enzymatic method compares favorably with a high-performance liquid chromatography assay.

The use of the colorimetric Jaffé method for the measurement of creatinine in mouse and rat plasma has been criticized as prior studies have shown a dramatic overestimation. We compared a colorimetric picric acid, an enzymatic, and a high-performance liquid chromatography (HPLC) method to assess their appropriateness for routine measurements of creatinine in plasma of healthy and diseased mice (n=61) and rats (n=56). For the colorimetric Jaffé method a pronounced overestimation is confirmed. Additionally the method showed interference with hemoglobin already in a very low, non-visible concentration range in rat plasma. The enzymatic measurement demonstrated a hemoglobin interference in mice, only when hemolysis was visible. The comparison between HPLC and the enzymatic measurement gave a good agreement between both methods in both species. Therefore the enzymatic method fulfills the requirements for a routine screening test for plasma creatinine in healthy as well as diseased mice and rats Kiover a broad concentration range.

Efficacy and immunogenicity of novel erythropoietic agents and conventional rhEPO in rats with renal insufficiency.

Recombinant human erythropoietin (rhEPO) is used to treat anemia in chronic renal insufficiency. Erythropoietin (EPO) immunogenicity can lead to EPO-resistant anemia. Conjugating proteins with polyethylene glycol (PEG) can prolong elimination half-life and diminish protein immunogenicity. We investigated the efficacy of new erythropoietic agents, synthesized by single (Ro 50-3821) and multiple (MIX) integrations of PEG and succinimidyl butanoic acid with rhEPO, in rats with chronic renal insufficiency. Sprague-Dawley rats with surgically induced renal insufficiency received Ro 50-3821 or MIX subcutaneously (s.c.) over 4-12 weeks compared to rhEPO and NaCl. Hemoglobin and antibody levels served as primary efficacy and safety variables. Dosing intervals and dose-response characteristics were investigated. Ro 50-3821 (2.5 microg/kg once weekly) increased hemoglobin levels by 7 g/dl after 4 weeks compared to 1 g/dl in NaCl controls (P<0.05). MIX (2.5 microg/kg once weekly) and rhEPO (0.25 microg/kg three times weekly) increased hemoglobin levels by 3 g/dl. Ro 50-3821 administered for 12 weeks (0.75 microg/kg once weekly) increased hemoglobin levels (from 13 to 19 g/dl) more effectively than rhEPO (0.75 microg/kg once weekly, decline from 13 to 11 g/dl, P<0.05). No antibodies against Ro 50-3821 were detected after 12 weeks of treatment. Antibodies against rhEPO were seen in 69% of animals (P<0.00001). Ro 50-3821 increased hemoglobin levels with once weekly s.c. dosing. Multiple pegylated EPO is less effective. In rats, rhEPO failed to increase hemoglobin levels with once weekly long-term dosing. Antibody formation following rhEPO may explain this finding. Therefore, Ro 50-3821 may provide important clinical advantages compared to unpegylated EPO. It can be administered in longer dosing intervals and has a lower risk of unfavorable immunological responses.

Kinase Receptor Activation (KIRA): a rapid and accurate alternative to endpoint bioassays.

We have developed a novel strategy for a rapid bioassay that is accurate, precise, sensitive, and high capacity. It is capable of quantifying ligand bioactivity by measuring ligand-induced receptor tyrosine kinase activation in terms of receptor-phosphorylation. The assay, termed << Kinase Receptor Activation>> or KIRA, uses two separate microtiter plates, one for ligand stimulation of intact cells, and the other for receptor capture and phosphotyrosine ELISA. The assay makes use of either endogenously expressed receptors or stably transfected receptors with a polypeptide flag. KIRA assays for the ligands IGF-I and NGF were compared to their corresponding endpoint bioassays (3T3 cell proliferation for IGF-I and PC12 cell survival for NGF). The KIRA assays showed excellent correlation with the more classical endpoint bioassays. Further, they were highly reproducible, minimizing the requirement for repeat assays. The KIRA assay format has great potential as a rapid, accurate and precise bioassay, both for potency determination as well as stability-indicating analyses.

[Radiotherapy in advanced osseous destruction in chronic myeloid leukemia. A case report]. / Radiotherapie bei fortgeschrittener ossärer Destruktion bei chronischer myeloischer Leukämie. Ein Fallbericht.

PURPOSE: Chronic myelocytic leukemia is a disease of myeloproliferative disorder. In chronic myelocytic leukemia occasionally myelosarcomas occur as defined tumors which can cause localized symptoms. We report a case of successful palliative radiotherapy. PATIENT AND METHODS: A 44-year-old patient with total destruction of the left humerus caused by myelosarcoma of the bone in chronic myelocytic leukemia was treated with percutaneous megavoltage radiotherapy, the total applied dose was 40 Gy. After radiotherapy the patient was free of pain. The tumorous swelling of soft tissue subsided completely, there was total formation of callus in the affected humerus and the patient could be mobilized. CONCLUSIONS: This case report confirms the high effectiveness of palliative radiotherapy even in advanced cases of myelosarcomas which has been described in literature.