3D versus 2D ultrasound: accuracy of volume measurement in human cadaver kidneys

RATIONALE AND OBJECTIVES: Comparison of the accuracy of 3D and 2D ultrasound in assessing the volume of human cadaver kidneys. MATERIALS AND METHODS: Before autopsy the volume of 22 kidneys was assessed from a 3D data set after manually tracing organ contours (3D volumetry) and by applying a 3D ellipsoid formula both on a 3D data set and 2D images. Measurements by water-displacement served as the gold standard. RESULTS: 3D volumetry showed a mean absolute deviation of 31 mL (18.5%) compared with the mean gold standard measurement (168 mL), yielding a concordance correlation (Lin's rho(c) ) of 0.71. Calculation based on the ellipsoid formula revealed a mean absolute deviation of 37 mL (22.0%) when applied on the 3D data set (rho(c) = 0.65) and of 42 mL (25.0%) when applied on 2D images (rho(c) = 0.61). CONCLUSIONS: 3D volumetry showed a satisfactory concordance correlation and is superior to volume calculation based on the ellipsoid formula either applied to a 3D data set or to conventional 2D images in assessing the volume of human cadaver kidneys.     

Neosordarin and hydroxysordarin,two new antifungal agents from Sordaria araneosa

Two novel antifungal agents belonging to the sordarin family have been isolated from fermentations of Sordaria araneosa by bioassay-guided purification and their structures elucidated by NMR techniques. Neosordarin (1) is closely related to the recently discovered hypoxysordarin (2), with only small differences on the aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose moiety. Hydroxysordarin (3) closely resembles sordarin (4), the only slight difference being the replacement of sordarose with altrose as the sugar unit.     

Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction

The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic double bond in the stabilization of Ras/Raf interaction was demonstrated. Variation of the size and the substituents of the cyclic system as well as the length of the carboxylic acid resulted in enhanced Ras/Raf interaction.     

Tumor M2 pyruvate kinase--determination in breast cancer patients receiving trastuzumab therapy

This study was designed to investigate the value of tumor M2 pyruvate kinase (tumor M2-PK) determination as an early marker for response to trastuzumab therapy in patients with metastasized breast cancer. Plasma samples of 20 trastuzumab patients were collected immediately after standard hematological investigations. The tumor M2-PK level was quantified using an enzyme linked immunosorbent assay (ScheBo Biotech) and CA 15-3 was measured automatically using the Bayer Immuno 1 immunoanalyzer and the corresponding assay. Each assay was performed in duplicate. The values were analyzed for correlation to the clinical course of each patient. Median observation time was 13 months with a range from 4 to 22 months. In 17/20 (85%) patients, tumor M2-PK determination was a marker for the clinical course of their disease. In this 'tumor M2-PK sensitive' group, 49 known clinical events (remission or progression according to UICC criteria) were recorded. The variation in tumor M2-PK level paralleled 63% of the clinical events (31/49). Our data suggest that tumor M2-PK determination in the plasma of patients with metastasized breast cancer could be a helpful tool for monitoring therapeutic success.     

Emerging therapeutic targets in chronic heart failure: part I

Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.     

Cellular senescence: a mechanism of the development of osteoporosis?

Osteoporosis is one of the most common diseases of the elderly. This leads to the hypothesis that the ageing of the organism is reflected as a cytogerontological effect in a specific loss of bone cell function. Three underlying pathogenetic mechanisms need to be considered: (1) cellular aging in general, (2) impairment of the systemic stimulation of bone formation by e.g. decreasing hormone levels, and (3) lower cellular effectiveness of cytokines and growth factors. Cellular aging consists of replicative and postmitotic senescence. While the replicative senescence limits only the number of cell cycles, the postmitotic aging is influenced by endo- and exogenous factors. These lead to genetic alterations known as delayed persistent genomic instability and to an increasing impairment of specific cellular functions. In the postmitotic phase, osteopenia caused by the decrease of systemically available sexual hormones is a major field of research. Osteopenia caused by a decreased activity of locally effective cytokines and growth factors is becoming increasingly understood. New therapeutic strategies, which modulate the local osteoblast activity, e.g. in bone defect healing, are under development. In conclusion, cellular senescence is considered to be one element in the development of bone loss. Potential therapeutic targets may open up an additional path in the treatment of local and systemic osteopenias.     

Mediastinale Hodgkin-Lymphome in der Computertomographie Vergleich von exakter CT-gestützter Volumetrie und Volumenabschätzung mit Hilfe einfacher geometrischer Modelle

BACKGROUND: The importance of the size of the primary tumor in lymphomas and its size after treatment is still uncertain. Assuming a prognostic relevance, an assessment of tumor volume before and after induction of chemotherapy has been performed in the pediatric Hodgkin's disease study (HD-90). Since an exact CT-scan-based volumetric tumor assessment is time-consuming and in some centers not possible, the tumor volume is often estimated based on simple geometric approximations. Aim of this study was the development of an easy to apply and nearly exact model of volume estimation compared to CT-scan-based tumor volume measurements. MATERIAL AND METHODS: Thirty computed tomographies (CT) of mediastinal Hodgkin lymphomas of children aged 5 to 16 years have been examined. The CT scans were digitalized using a CCD camera combined with a frame grabber. Applying the Global Lab image software, the true tumor volume was determined excluding local organs, which did not belong to the lymphoma. Subsequently, volumes were assessed using simple geometric models (block, ellipsoid, octaeder) by using the maximum diameters of the tumor. The differences between the volume of the geometric models and the true volume, based on the CT scan evaluation, were compared. RESULTS: The maximum diameters of a tumor can be used to calculate its volume based on simple geometric models. The model "block" overestimates the volume by 89 to 268%. The model "ellipsoid" overestimates the volume on average by 29%. The model "octaeder" underestimates the volume on average by 18%. A division of the block volume by 2.3 approximated the geometric closest to the true volume: the average volume was overestimated by 2% in tumors with a volume larger than 20 ml. No model was sufficient to approximate tumors with a volume of less than 20 ml. CONCLUSIONS: For the estimation of tumor volumes in mediastinal Hodgkin lymphomas exceeding 20 ml, the formula "block/2.3" results in the closest approximation compared to the true volume. In the course of clinical studies it might be helpful to apply this formula to determine the prognostic relevance of the tumor size and its development under therapy.     

Bioactive sesquiterpenes from the basidiomycete Resupinatus leightonii

1(10),4-Germacradiene-2,6,12-triol (1), a new germacrane sesquiterpene, and 1,6-farnesadiene-3,10,11-triol (2), a known nerolidol derivative, were isolated from submerged cultures of the basidiomycete Resupinatus leightonii. Both compounds inhibited cAMP-induced appressorium formation in Magnaporthe grisea and showed cytotoxic activity. The structure of 1 was determined by NMR and mass spectroscopic methods.     

Abnormal length of cilia—a cause of primary ciliary dyskinesia—a case report

A 7-year-old Turkish boy had suffered from chronic coughing from early childhood. Severe bronchiectasis in the right lung was confirmed by bronchography. Ciliary beat frequency determined in a bronchial mucosal biopsy was markedly decreased (5.7 Hz). Electron microscopy revealed cilia with a length of 15 m. No structural abnormality was found. A possible link between the abnormally long, slow beating cilia and the clinical symptoms is discussed.