Origin and evolution of the deep thermochemical structure beneath Eurasia.

A unique structure in the Earth's lowermost mantle, the Perm Anomaly, was recently identified beneath Eurasia. It seismologically resembles the large low-shear velocity provinces (LLSVPs) under Africa and the Pacific, but is much smaller. This challenges the current understanding of the evolution of the plate-mantle system in which plumes rise from the edges of the two LLSVPs, spatially fixed in time. New models of mantle flow over the last 230 million years reproduce the present-day structure of the lower mantle, and show a Perm-like anomaly. The anomaly formed in isolation within a closed subduction network ∼22,000 km in circumference prior to 150 million years ago before migrating ∼1,500 km westward at an average rate of 1 cm year-1, indicating a greater mobility of deep mantle structures than previously recognized. We hypothesize that the mobile Perm Anomaly could be linked to the Emeishan volcanics, in contrast to the previously proposed Siberian Traps.

In vitro and in vivo neo-cartilage formation by heterotopic chondrocytes seeded on PGA scaffolds.

Implantation of tissue-engineered heterotopic cartilage into joint cartilage defects might be an alternative approach to improve articular cartilage repair. Hence, the aim of this study was to characterize and compare the quality of tissue-engineered cartilage produced with heterotopic (auricular, nasoseptal and articular) chondrocytes seeded on polyglycolic acid (PGA) scaffolds in vitro and in vivo using the nude mice xenograft model. PGA scaffolds were seeded with porcine articular, auricular and nasoseptal chondrocytes using a dynamic culturing procedure. Constructs were pre-cultured 3 weeks in vitro before being implanted subcutaneously in nude mice for 1, 6 or 12 weeks, non-seeded scaffolds were implanted as controls. Heterotopic neo-cartilage quality was assessed using vitality assays, macroscopical and histological scoring systems. Neo-cartilage formation could be observed in vitro in all PGA associated heterotopic chondrocytes cultures and extracellular cartilage matrix (ECM) deposition increased in vivo. The 6 weeks in vivo incubation time point leads to more consistent results for all cartilage species, since at 12 weeks in vivo construct size reductions were higher compared with 6 weeks except for auricular chondrocytes PGA cultures. Some regressive histological changes could be observed in all constructs seeded with all chondrocytes subspecies such as cell-free ECM areas. Particularly, but not exclusively in nasoseptal chondrocytes PGA cultures, ossificated ECM areas appeared. Elastic fibers could not be detected within any neo-cartilage. The neo-cartilage quality did not significantly differ between articular and non-articular chondrocytes constructs. Whether tissue-engineered heterotopic neo-cartilage undergoes sufficient transformation, when implanted into joint cartilage defects requires further investigation.

[Accuracy of rotational positioning of the femoral component using the tibial-cut-first technique]. / Bestimmung der Rotationsgenauigkeit der Femurkomponente bei Tibial-Cut-First-Technik.

AIM: Problems with the patellofemoral joint are still one of the most common difficulties after total knee arthroplasty. One of the main reasons for these problems seems to be the rotatory malposition of the femoral component. We examined the rotation of the femoral component and the symmetry of the flexion gap of knee prostheses implanted using the tibial-cut-first technique. METHOD: The radiographs of 58 consecutive patients who underwent primary LCS total knee arthroplasty in 2008 were examined retrospectively. The rotation of the femoral component was determined intraoperatively using the femoral positioner and depended on the amount of tibial resection and the tension of the collateral ligaments. The position was then checked by means of three anatomic landmarks: the epicondylar axis, the posterior condyles and the Whiteside line. We used Kanekasu's technique for the radiographs. With this technique it was possible to ascertain the rotation of the femoral component after total knee arthroplasty easily and with a low level of radiation. It was also possible to determine the opening of the flexion gap. RESULTS: The radiographs showed a slight external rotation of the femoral component of 1.31°. The opening of the flexion gap was increased laterally, but only by 1.5°. CONCLUSION: In this study, determination of femoral rotation using the tibial-cut-first technique resulted in a slight external rotation of the femoral component. Furthermore, it is possible to create an almost symmetrical flexion gap with this method.

Differing in vitro biology of equine, ovine, porcine and human articular chondrocytes derived from the knee joint: an immunomorphological study.

For lack of sufficient human cartilage donors, chondrocytes isolated from various animal species are used for cartilage tissue engineering. The present study was undertaken to compare key features of cultured large animal and human articular chondrocytes of the knee joint. Primary chondrocytes were isolated from human, porcine, ovine and equine full thickness knee joint cartilage and investigated flow cytometrically for their proliferation rate. Synthesis of extracellular matrix proteins collagen type II, cartilage proteoglycans, collagen type I, fibronectin and cytoskeletal organization were studied in freshly isolated or passaged chondrocytes using immunohistochemistry and western blotting. Chondrocytes morphology, proliferation, extracellular matrix synthesis and cytoskeleton assembly differed substantially between these species. Proliferation was higher in animal derived compared with human chondrocytes. All chondrocytes expressed a cartilage-specific extracellular matrix. However, after monolayer expansion, cartilage proteoglycan expression was barely detectable in equine chondrocytes whereby fibronectin and collagen type I deposition increased compared with porcine and human chondrocytes. Animal-derived chondrocytes developed more F-actin fibers during culturing than human chondrocytes. With respect to proliferation and extracellular matrix synthesis, human chondrocytes shared more similarity with porcine than with ovine or equine chondrocytes. These interspecies differences in chondrocytes in vitro biology should be considered when using animal models.

IL-10 overexpression differentially affects cartilage matrix gene expression in response to TNF-alpha in human articular chondrocytes in vitro.

Cartilage-specific extracellular matrix synthesis is the prerequisite for chondrocyte survival and cartilage function, but is affected by the pro-inflammatory cytokine TNF-alpha in arthritis. The aim of the present study was to characterize whether the immunoregulatory cytokine IL-10 might modulate cartilage matrix and cytokine expression in response to TNF-alpha. Primary human articular chondrocytes were treated with either recombinant IL-10, TNF-alpha or a combination of both (at 10ng/mL each) or transduced with an adenoviral vector overexpressing human IL-10 and subsequently stimulated with 10ng/ml TNF-alpha for 6 or 24h. The effects of IL-10 on the cartilage-specific matrix proteins collagen type II, aggrecan, matrix-metalloproteinases (MMP)-3, -13 and pro-inflammatory cytokines were evaluated by real-time RT-PCR and immunohistochemistry. Transduced chondrocytes overexpressed high levels of IL-10 which significantly up-regulated collagen type II expression. TNF-alpha suppressed collagen type II and aggrecan, but increased MMP and cytokine expression in chondrocytes compared to the non-stimulated controls. The TNF-alpha mediated down-regulation of aggrecan expression was significantly antagonized by IL-10 overexpression, whereas the suppression of collagen type II was barely affected. The MMP-13 and IL-1beta expression by TNF-alpha was slightly reduced by IL-10. These results suggest that IL-10 overexpression modulates some catabolic features of TNF-alpha in chondrocytes.

Interleukin-10 modulates pro-apoptotic effects of TNF-alpha in human articular chondrocytes in vitro.

The aim of this study is to determine if there is an antagonistic effect between tumour necrosis factor (TNF)-alpha and the immunoregulatory interleukin (IL)-10 on chondrocytes survival. Serum-starved primary human articular chondrocytes were stimulated with either 10 ng/ml recombinant TNF-alpha, IL-10 or a combination of both (at 10 ng/ml each). Chondrocyte apoptosis was determined by measuring caspase-3/7, -8 and -9 activities using caspase assays. Mitochondrial apoptotic inducer bax, and the suppressor bcl-2 were evaluated using western blotting at 48 h. Results indicated that TNF-alpha increased caspase activities and resulted in a significant (p = 0.001) increase in bax/bcl-2 ratio. Stimulation with IL-10 did not alter caspase activities, while co-treatment with IL-10 and TNF-alpha inhibited TNF-alpha induced caspase activities and significantly (p > 0.004) impaired bax/bcl-2 ratio. At 24 h, mRNA levels for collagen type II, TNF-alpha and IL-10 were determined using real-time RT-PCR. Stimulation with TNF-alpha or TNF-alpha and IL-10 significantly inhibited collagen type II and increased IL-10 and TNF-alpha mRNA expression. IL-10 modulated the pro-apoptotic capacity of TNF-alpha in chondrocytes as shown by the decrease in caspase activities and bax/bcl-2 ratio compared to TNF-alpha stimulated chondrocytes, suggesting a mostly antagonistic interplay of IL-10 and TNF-alpha on mitochondrial apoptotic pathways.

Major Australian-Antarctic plate reorganization at Hawaiian-Emperor bend time.

A marked bend in the Hawaiian-Emperor seamount chain supposedly resulted from a recent major reorganization of the plate-mantle system there 50 million years ago. Although alternative mantle-driven and plate-shifting hypotheses have been proposed, no contemporaneous circum-Pacific plate events have been identified. We report reconstructions for Australia and Antarctica that reveal a major plate reorganization between 50 and 53 million years ago. Revised Pacific Ocean sea-floor reconstructions suggest that subduction of the Pacific-Izanagi spreading ridge and subsequent Marianas/Tonga-Kermadec subduction initiation may have been the ultimate causes of these events. Thus, these plate reconstructions solve long-standing continental fit problems and improve constraints on the motion between East and West Antarctica and global plate circuit closure.

[Right to health. Perspective of the statutory health insurance]. / Recht auf Gesundheit. Perspektive einer gesetzlichen Krankenkasse.

This essay is concerned with the topic 'right to health' from the perspective of a health insurance company. Following an outline of the legal foundation, aspects regarding benefit restrictions within the context of the contemporary political health discourse are discussed. The AOK's viewpoints and demands regarding patient sovereignty are represented under the rubrics of: information and transparency, consumer protection and self-help groups, quality of health care, treatment error management, doctor contract codification, error reduction management and expanding avenues for participation. The section "Health insurance companies fortify patient rights" exemplifies the efforts and activities of the AOK Berlin. These include the Disease Management Program Breast Cancer, a patient survey regarding home nursing care, and AOK Berlin's contributions to "A Healthy City" - a project based on the initiative of the WHO's Ottawa Charta. Furthermore, "prevention" and "setting" proposals, treatment error management, and complaint management are presented. In conclusion, the goals of deploying patient sovereignty, taking into consideration essential limitations of health insurance benefits, are redeveloped and linked with the demands for further development of patient rights.

Adenoviral transduction is more efficient in alginate-derived chondrocytes than in monolayer chondrocytes.

Gene transfer into cultured chondrocytes by using adenoviral vectors has potential applications in treating cartilage disorders. The present study was undertaken to compare and optimize two chondrocyte culture conditions for adenoviral transduction efficacy by using primary human articular chondrocytes cultivated either directly in a monolayer condition or as outgrowths from alginate-stored chondrocyte cultures. Isolated primary chondrocytes from human articular cartilage were either immediately transduced with an EGFP (enhanced green fluorescent protein)-gene-bearing adenoviral vector (1,000 and 3,000 virus particles/cell) or cultured in alginate before transduction. Immunohistochemistry and flow cytometric analysis were employed to determine the expression of extracellular matrix proteins and of the alphavbeta5 integrin receptor involved in adenoviral cell entry. Monolayer chondrocytes exhibited moderate transduction rates (mean 22.2% and 46.9% EGFP-positive cells at 1,000 and 3,000 virus particles/cell by 72 h post-transduction), whereas alginate-derived chondrocytes revealed significantly higher transduction efficacies (95.7% and 99%). Both monolayer and alginate-derived chondrocytes expressed alphavbeta5 integrin, type II collagen and cartilage proteoglycans. The mean fluorescence intensity of type II collagen was significantly higher in the alginate-derived chondrocytes, whereas that of alphavbeta5 integrin was higher in the monolayer chondrocytes. Our results indicate that transduction efficacy is independent of alphavbeta5 integrin expression levels in chondrocytes. Moreover, adenoviral transduction of alginate-derived chondrocytes is more efficient than that for monolayer chondrocytes and may be a suitable tool to achieve sufficient numbers of transduced and differentiated chondrocytes for experimental applications and cartilage repair.

[Intravenous contrast medium application in elderly patients -- evaluation of Iopentol (Imagopaque 300)]. / Intravenöse Kontrastmittel-Applikation bei älteren Patienten -- Anwendungsbeobachtung von Iopentol (Imagopaque 300).

PURPOSE: We examined the subjective compatibility of elderly patients who received the intravenous contrast medium Iopentol (Imagopaquetrade mark 300). In addition, objective data were aquired to show possible interactions between contrast media and organ systems in old patients. METHODS AND MATERIALS: A CT scan with intravenous application of contrast media was performed on 132 patients ranging in age from 75 to 96 years. The patients were questioned about their individual sensations. In addition, blood pressure, creatinine and CT-densitometry were acquired as objective data. RESULTS: The patients' individual sensations and clinical data show a very low rate of complications. Mild allergic reactions were noticed in two patients. No severe anaphylactic reactions were encountered. Statistically significant changes in blood pressure before and after administration of the contrast medium were not observed. The serum creatinine concentration was unchanged after application of contrast media. For CT-densitometry, the patients were divided into two groups, one group with patients 75 - 84 years and the other group with patients 85 - 96 years of age. CT-densitometry showed no age-related differences. The protocol of contrast administration resulted in excellent opacification of the examined regions, only the liver did not enhance in some cases before the opacification of the portal vein. CONCLUSION: It is shown that old age alone is no reason to withhold contrast media containing iodine when performing CT. For the evaluation of the liver, however, the peculiarities of old age have to be taken into account and the interval between injection of the contrast medium and beginning of the spiral-CT has to be extended.

Successful interventional treatment of renal insufficiency caused by renal artery pseudoaneurysm with concomitant arteriovenous fistula.

Asymptomatic arteriovenous fistulae and pseudoaneurysms are common after renal biopsy. We present a patient with a single kidney and symptomatic pseudoaneurysm of the renal artery with concomitant arteriovenous fistula as a rare complication following surgical embolectomy. The patient developed renal insufficiency because of a significant degree of vascular steal caused by the fistula. Dialysis was performed for more than 6 months until the fistula was diagnosed. The fistula and the pseudoaneurysm were successfully treated by superselective arterial embolization with metallic coils. Renal function improved within the next 2 weeks and no further dialysis was necessary.

SPIO-MR imaging versus double-phase spiral CT in detecting malignant lesions of the liver.

PURPOSE: To assess the diagnostic performance of superparamagnetic iron oxide MR (SPIO-MR) imaging compared with double-phase spiral CT in detecting liver metastases and hepatocellular carcinoma. MATERIAL AND METHODS: Thirty-eight patients with a total of 144 malignant lesions of the liver were examined by CT and SPIO-MR. After definition of a gold standard by a panel of experts, the patient images were randomized and presented to a blinded jury of 5 independent observers whose task was to identify as many lesions as possible. The results were tested for statistical significance using multifactorial analysis of variance (alpha=5%). RESULTS: SPIO-MR produced the highest detection rate and was significantly superior (p<0.05) to unenhanced MR imaging and double spiral-phase contrast-enhanced CT (DPS-CECT). Maximum performance in DPS-CECT was obtained during the portal venous contrast phase but was significantly inferior to SPIO-MR imaging. The scores for unenhanced CT and unenhanced MR were significantly lower than for the corresponding enhanced procedures. SPIO-MR imaging produced a higher incidence of false-positive findings (n=39). CONCLUSION: SPIO-MR produced a significantly better detection rate for malignant focal liver lesions compared with double-phase spiral DPS-CECT but was associated with a higher rate of false-positive findings.

Prophylactic cranial irradiation in locally advanced non-small-cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuropsychologic effects.

PURPOSE: Relapse pattern and late toxicities in long-term survivors were analyzed after the introduction of prophylactic cranial irradiation (PCI) into a phase II trial on trimodality treatment of locally advanced (LAD) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Seventy-five patients with stage IIIA(N2)/IIIB NSCLC were treated with induction chemotherapy, preoperative radiochemotherapy, and surgery. PCI was routinely offered during the second period of study accrual. Patients were given a total radiation dose of 30 Gy (2 Gy per daily fraction) over a 3-week period starting 1 day after the last chemotherapy cycle. RESULTS: Introduction of PCI reduced the rate of brain metastases as first site of relapse from 30% to 8% at 4 years (P =.005) and that of overall brain relapse from 54% to 13% (P <.0001). The effect of PCI was also observed in the good-prognosis subgroup of 47 patients who had a partial response or complete response to induction chemotherapy, with a reduction of brain relapse as first failure from 23% to 0% at 4 years (P =.01). Neuropsychologic testing revealed impairments in attention and visual memory in long-term survivors who received PCI as well as in those who did not receive PCI. T2-weighted magnetic resonance imaging revealed white matter abnormalities of higher grades in patients who received PCI than in those who did not. CONCLUSION: PCI at a moderate dose reduced brain metastases in LAD-NSCLC to a clinically significant extent, comparable to that in limited-disease small-cell lung cancer. Late toxicity to normal brain was acceptable. This study supports the use of PCI within intense protocols for LAD-NSCLC, particularly in patients with favorable prognostic factors.

[Low-dosage dental CT]. / Niedrigdosis Dental-CT.

PURPOSE: The intention of this study was to reduce patient dose during dental CT in the planning for osseointegrated implants. METHODS AND MATERIALS: Dental CTs were performed with a spiral CT (Somatom Plus 4, Siemens) and a dental software package. Use of the usual dental CT technique [1] (120 kVp; 165 mA, 1 s rotation time, 165 mAs; pitch factor 1) was compared with a new protocol (120 kVp; 50 mA; 0.7 s rotation time; 35 mAs; pitch factor 2) which delivered the best image quality at the lowest possible radiation dose, as tested in a preceding study. Image quality was analysed using a human anatomic head preparation. Four radiologists analysed the images independently. A Wilcoxon rank pair-test was used for statistic evaluation. The doses to the thyroid gland, the active bone marrow, the salivary glands, and the eye lens were determined in a tissue-equivalent phantom (Alderson-Rando Phantom) with lithium fluoride thermoluminescent dosimeters at the appropriate locations. RESULTS: By mAs reduction from 165 to 35 and using a pitch factor of 2, the radiation dose could be reduced by a factor of nine (max.) (e.g., the bone marrow dose could be reduced from 23.6 mSv to 2.9 mSv, eye lens from 0.5 mSv to 0.3 mSv, thyroid gland from 2.5 mSv to 0.5 mSv, parotid glands from 2.3 mSv to 0.4 mSv). The dose reduction did not lead to an actual loss of image quality or diagnostic information. CONCLUSION: A considerable dose reduction without loss of diagnostic information is achievable in dental CT. Dose-reducing examination protocols like the one presented may further expand the use of preoperative dental CT.

Prospective randomized study for an injection protocol for intravenous contrast media in abdominal and pelvic helical CT.

OBJECTIVE: To develop an injection protocol for intravenous administration of contrast media in abdominal and pelvic helical CT which provides optimal contrast enhancement of arterial and venous vessels. MATERIAL AND METHODS: For the study on a Somatom Plus 4 unit, a standard helical CT examination procedure of abdomen and pelvis consisted firstly of a native helical examination of the liver, a second one of the liver after intravenous injection of 120 ml nonionic contrast medium with a constant start delay of 50 s, and subsequently a third helical CT of the lower abdomen and pelvis. 125 patients were randomized for examination under different protocols, varying the injection flow from 2.0-4.0 ml/s and the time delay between the second and the third helical examinations from an additional 20-40 s. The efficacy of the contrast injection was checked by region of interest (ROI) measurements of HUs in aorta, inferior vena cava, and in femoral arteries and veins. The results were compared by t-test statistics. RESULTS: A slow flow rate of 2.0 ml/s led to a higher contrast enhancement in the aorta than a flow rate of 3.0 and 4.0 ml/s. The difference between 2.0 ml/s and 4.0 ml/s was statistically significant. In the inferior vena cava, a flow of 3.0 ml/s caused a better contrast than a flow of 2.0 ml/s or 4.0 ml/s, but the measurements did not reach statistical significance. The measurements in the femoral arteries and veins did not show any significant differences. Maximal enhancement in the pelvic vessels was achieved when the third helical examination was started immediately after the second one had ended. Adding any delay (20 s, 40 s) led to a reduced contrast in the pelvic vessels, with a significant reduction in aorta and femoral arteries. CONCLUSION: For routine abdominal and pelvic helical CT, we recommend an injection of 120 ml contrast medium with a flow rate of 3.0 ml/s. Contrast-enhanced examination of the liver should be started after 50 s, and examination of the lower abdomen and pelvis region should be performed without any further delay. This gives an appropriate contrast in the major vessels.

Impact of CT in patients with sepsis of unknown origin.

PURPOSE: To evaluate the diagnostic relevance of CT in patients with sepsis of unknown origin. MATERIAL AND METHODS: Sixty-three consecutive intensive care patients with suspicion of an abscess and negative or inconclusive previous radiological examinations were included. CT was performed using the helical technique. A total of 45 abdominal and 38 chest examinations were evaluated. RESULTS: 5/38 examinations of the chest revealed the source of sepsis (pleural empyema 2, lung abscess 1, mediastinitis 1, retrosternal abscess 1). 7/45 abdominal CT examinations showed the source of sepsis (intraabdominal abscess 2, hepatic abscess 3, intestinal perforation 1, gangrenous colitis 1). CONCLUSION: CT is useful for the evaluation of patients with fever or sepsis without a known source. Due to the detection of a septic focus by CT, 19% of the patients in our study could be immediately referred to causal therapy as percutaneous drainage or surgery.

[3D-computed tomography for spatial arrangement of the cranial bones of the human fetus]. / Die 3D-Computertomographie zur räumlichen Darstellung des Kopfskelettes eines menschlichen Feten.

Aim of the study was to assess the value of in vitro three-dimensional computed tomography (3D-CT) as a new method for the depiction of the fetal skull. 3D-CT images of a fetal head of 24 weeks gestational age were generated with the implemented software on the basis of contiguous CT slices of 1 mm thickness. 3D-CT gave real three-dimensional information about morphology and spatial arrangement of the cranial bones. Using cutting and rotating procedures fast evaluation of all imaged ossified structures in arbitrary views without disturbing superpositions was possible, thus allowing easy identification and accurate description of the cranial bones and making isolated examinations of particular macroscopic sections of the specimens unnecessary. Advantages of 3D-CT over other evaluation techniques for the fetal cranium and its limitations are discussed. In conclusion, 3D-CT promises to be an effective tool for the investigation of fetal cranial development.

[CT densitometry for the grading of subcutaneous fibrosis after the photon-neutron therapy of malignant salivary gland tumors]. / CT-Dichtemessungen zur Graduierung subkutaner Fibrosen nach Photonen-Neutronen-Therapie maligner Speicheldrüsentumoren.

BACKGROUND: To evaluate alternative treatment regimen e.g. neutron therapy determination of treatment efficacy as well as side effects is important. Sensitivity of computed tomography (CT) in detecting changes of connective tissue after neutron therapy was examined. PATIENTS AND METHODS: In the course of their follow-up period (median 45 months) 12 patients with malignant salivary gland tumors who had postoperatively received neutron (1/12) or photon/neutron therapy (11/12) were examined by means of CT densitometry on 3 representative scans in the area of radiotherapy. In 3 ROI (regions of interest) in subcutaneous fatty tissue the density at the irradiated and the non-irradiated side was determined according to Hounsfield units (HU) and the average density was calculated. The average density of both sides was compared and correlated with the clinical grade of fibrosis according to LENT SOMA. RESULTS: All CT measurements (216 ROI, 18 ROI per patient) showed higher density levels on the irradiated side than on the non-irradiated side. The average density on the irradiated side was -57.7 +/- 4.7 HU and on the non-irradiated side -69.4 +/- 5.8 HU (p = 0.002). In 3/12 patients a clinical fibrosis was not seen; however, the relative density measured on the irradiated and non-irradiated side deviated by up to 8%. This could have been caused by minimal changes not being noticed by either patient and examiner. In patients with determined fibrosis Grade 1 (8/12) the relative density deviation was 4 to 39%. In 1/12 patients with determined fibrosis Grade 2 the relative density deviation was 50% (Figures 1a and 1b). Fibrosis Grade 3 and 4 did not occur (Table 1). CONCLUSIONS: Fibrosis is correlated with an increasing value of HU of the tissue density in CT. With the described method it is possible to graduate radiation induced subcutaneous fibrosis in correlation to the clinical fibrosis grade according to LENT SOMA. In the patients we examined subcutaneous fibroses after photon/neutron therapy were moderate. Especially in characterising subclinical or slight changes of connective tissue after radiotherapy computed tomography is of value.