STED properties of Ce3+, Tb3+, and Eu3+ doped inorganic scintillators.

Scintillator-based X-ray imaging is a powerful technique for noninvasive real-space microscopic structural investigation such as synchrotron-based computed tomography. The resolution of an optical image formed by scintillation emission is fundamentally diffraction limited. To overcome this limit, stimulated scintillation emission depletion (SSED) X-ray imaging, based on stimulated emission depletion (STED) microscopy, has been recently developed. This technique imposes new requirements on the scintillator material: efficient de-excitation by the STED-laser and negligible STED-laser excited luminescence. In this work, luminescence depletion was measured in several commonly-used Ce3+, Tb3+, and Eu3+ - doped scintillators using various STED lasers. The depletion of Tb3+ and Eu3+ via 4f-4f transitions was more efficient (Ps = 8…19 mW) than Ce3+ depletion via 5d-4f transitions (Ps = 43…45 mW). Main origins of STED-laser excited luminescence were one- and two-photon excitation, and scintillator impurities. LSO:Tb scintillator and a 628 nm cw STED-laser is the most promising combination for SSED satisfying the above-mentioned requirements.

Tb3+-doped LaF3 nanocrystals for correlative cathodoluminescence electron microscopy imaging with nanometric resolution in focused ion beam-sectioned biological samples.

Here, we report the use of rare earth element-doped nanocrystals as probes for correlative cathodoluminescence electron microscopy (CCLEM) bioimaging. This first experimental demonstration shows potential for the simultaneous acquisition of luminescence and electron microscopy images with nanometric resolution in focused ion beam cut biological samples.

Hyperacute Vasospasm After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Cerebral vasospasm after aneurysmal subarachnoid hemorrhage typically occurs 3-14 days after aneurysm rupture. We describe a series of patients who developed vasospasm within minutes of aneurysm rupture. This phenomenon, which we term, "hyperacute vasospasm," has been reported in animal models of SAH, but hitherto has been poorly described in humans. METHODS: Eleven patients were identified from an institutional registry who had aneurysmal rupture during catheter cerebral angiography between 1997 and 2009. We quantified the degree of vasoconstriction using vascular diameter index (VDI). The change in VDI (delta VDI or DVDI) was calculated by determining the difference in VDI before and after the procedure. We also examined the relationship between hyperacute vasospasm and delayed cerebral ischemia. RESULTS: Ten of eleven (91%) patients with intraoperative aneurysm rupture had cerebral vasoconstriction within minutes of intra-procedural aneurysmal rupture. Six of eleven patients (55%) with hyperacute vasospasm developed delayed cerebral infarction. CONCLUSIONS: Hyperacute vasospasm is likely common in patients with intraoperative aneurysm rupture and may be an unrecognized element of the natural history of aneurysmal subarachnoid hemorrhage. In this limited series, there was an association between hyperacute vasospasm and delayed cerebral infarction.

Master triathletes have not reached limits in their Ironman triathlon performance.

The purpose of this study was to analyze the participation and performance trends of male triathletes in the "Ironman Switzerland" from 1995 to 2010. Participation trends of all finishers aged between 18 and 64 years were analyzed over the 16-year period by considering four 4-year periods 1995-1998, 1999-2002, 2003-2006, and 2007-2010, respectively. The 3.8-km swimming, 180-km cycling, 42-km running times, and total race times were analyzed for the top 10 triathletes in each age group from 18 to 64 years. The participation of master triathletes (≥40 years old) increased over the years, representing on average 23%, 28%, 37%, and 48% of total male finishers during the four 4-year periods, respectively. Over the 1995-2010 period, triathletes older than 40 years significantly improved their performance in swimming, cycling, running, and in the total time taken to complete the race. The question whether master Ironman triathletes have yet reached limits in their performance during Ironman triathlon should be raised. Further studies investigating training regimes, competition experience, or socio-demographic factors are needed to gain better insights into the phenomenon of the relative improvement in ultra-endurance performance with advancing age.

Retrospective lifetime estimation of failed and explanted diamond-like carbon coated hip joint balls.

Diamond-like carbon (DLC) coatings are known to have extremely low wear in many technical applications. The application of DLC as a coating has aimed at lowering wear and to preventing wear particle-induced osteolysis in artificial hip joints. In a medical study femoral heads coated with diamond-like amorphous carbon, a subgroup of DLC, articulating against polyethylene cups were implanted between 1993 and 1995. Within 8.5 years about half of the hip joints had to be revised due to aseptic loosening. The explanted femoral heads showed many spots of local coating delamination. Several of these explanted coated TiAlV femoral heads have been analyzed to investigate the reason for this failure. Raman analysis and X-ray photoelectron spectroscopy (XPS) depth profiling showed that the coating consists of diamond-like amorphous carbon, several Si-doped layers and an adhesion-promoting Si interlayer. Focused ion beam (FIB) transverse cuts revealed that the delamination of the coatings is caused by in vivo corrosion of the Si interlayer. Using a delamination test set-up dissolution of the silicon adhesion-promoting interlayer at a speed of more than 100 µm year(-1) was measured in vitro in solutions containing proteins. Although proteins are not directly involved in the corrosion reactions, they can block existing small cracks and crevices under the coating, hindering the exchange of liquid. This results in a build-up of crevice corrosion conditions in the crack, causing a slow dissolution of the Si interlayer.

High dose methotrexate treatment in childhood ALL: pilot study on the impact of the MTHFR 677C>T and 1298A>C polymorphisms on MTX-related toxicity.

Methotrexate (MTX) is commonly administered in high doses for treatment of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to study the influence of 2 common MTHFR polymorphisms (MTHFR 677C>T and 1298 A>C) on MTX toxicity in children with ALL.Retrospective analysis of 129 MTX courses in 34 pediatric patients with ALL.677C>T variants (CT or TT) were found in 19 (14 heterozygous, 5 homozygous) and 1298A>C variants (AC or CC) in 20 (16 heterozygous, 4 homozygous) patients. The MTHFR 677C>T wild type was associated with an increased frequency of grade III and IV leukopenia (60% vs. 31%, p<0.05) compared to the variants. The rate of severe infections (21% vs. 0%, p<0.05) and grade III-IV anemia (26% vs. 5%, p<0.05) was increased in carriers of the MTHFR 677C>T wild type compared to patients with the TT variant. Grade III-IV anemia was more frequent in patients with the MTHFR 1298A>C CC variant compared to the wild type (56% vs. 21%, p<0.05). The differences were not significant in a patient-based analysis.MTX related toxicity might be influenced by the MTHFR 677C>T or the MTHFR 1298A>C polymorphisms. Differences in MTX toxicity are only partially explainable by these 2 polymorphisms.

Acute psychosis in an adolescent girl during treatment for advanced nodular lymphocyte-predominant Hodgkin's lymphom.

A 16,5 year old female adolescent was diagnosed with nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL), presenting bilateral inguinal and right iliac lymphadenopathy accompanied by B-symptoms. The patient was due to treatment according to the German Interim Guidelines of HD 2002-Pilot Study with 2x OPPA (vincristine, adriamycine, prednisone, procarbacine) and 2x COPP (cyclophosphamide, vincristine, prednisone, procarbazine) and radiotherapy. After 2x OPPA the patient presented a severe episode of a presumably prednisone-induced acute psychosis with need for psychiatric treatment and change of therapy regimen. She was successfully treated with a chimeric monoclonal anti-CD20 antibody (rituximab) and subsequent radiotherapy.

Management of oncology patients admitted to the paediatric intensive care unit of a general children's hospital - a single center analysis.

BACKGROUND: The improving prognosis of children with cancer has partially been attributed to the increasing importance of pediatric intensive care units (PICU). We analyze whether outcome of these patients on a PICU improved during the last decade and which factors may influence the outcome in our hospital. PATIENTS AND METHODS: The charts of all oncology patients admitted to the PICU between 1998 and 2009 have been reviewed retrospectively. The survival of patients admitted for life threatening complications has been correlated with basic data, organ failure and the PRISM score. The results of 2 consecutive treatment periods (1998-2003 and 2004-2009) were compared. RESULTS: 644 admissions of 226 patients were recorded. 79 admissions were performed because of potentially life threatening complications (Group A), 236 for monitoring (B) and 329 admissions for interventions (C). 62% of Group A patients and all Group B and C patients were discharged alive. Poor outcome was associated with admission >28 days after initial diagnosis, PRISM >10, organ failure >2 organs, sepsis, allogeneic stem cell transplantation, need for mechanical ventilation or for catecholamines. The PICU survival rate of Group A patients admitted between 2004 and 2009 (78%) was higher than in the period between 1998 and 2003 (48%). CONCLUSIONS: PICU provides essential services to support the pediatric oncology ward. Although children with cancer may have had benefit from advances in pediatric intensive care over the past decade, specific scoring systems for early identification of children with cancer needing PICU treatment are required. These systems might further improve PICU outcome in critical ill pediatric cancer patients.

[Immune tolerance induction with high-dose FVIII and pulsed intravenous immunoglobulin]. / Immuntoleranzinduktion mit hoch dosiertem FVIII und intravenösen Immunglobulin-Pulsen. Ein Patient mit Hemmkörper-Hämophilie A.

UNLABELLED: The development of neutralizing allo-antibodies against factor VIII (FVIII) or FVIII inhibitors is a severe complication in the treatment of haemophilia A. About 25% of the children with severe haemophilia A develop FVIII inhibitors. Here we report on a boy with severe haemophilia A and intron 22 inversion of the FVIII gene who was diagnosed at ten months of age. After 16 exposure days to FVIII (81 days after initial exposure) he developed a FVIII inhibitor (maximum: 9.76 BU/ml). THERAPY: We started immune tolerance induction (ITI) according to the Bonn protocol with high dose plasma derived FVIII concentrate (100 IU per kg body weight) twice daily. For additional inhibitor elimination treatment the patient received intravenous immunoglobulin (ivIg) at a dose of 1-2 g/kg body weight every 4 to 6 weeks. After start of treatment a rapid decline of the inhibitor level was observed, nevertheless low FVIII inhibitor levels persisted (<5 BU/ml). Furthermore, the FVIII half-life was still accelerated. However, after every course of ivIg the inhibitor level declined and FVIII half-life was prolonged. Currently, the FVIII half-life is approaching normal values after more than seven months of ITI duration. CONCLUSION: Additional application of immunoglobulin is beneficial for immune tolerance induction.

Cumulative radiation dose in patients admitted with subarachnoid hemorrhage: a prospective study using a self-developing film badge.

BACKGROUND AND PURPOSE: While considerable attention has been directed to reducing the x-ray dose of individual imaging studies, there is little information available on the cumulative dose during imaging-intensive hospitalizations. We used a radiation-sensitive badge on 12 patients admitted with SAH to determine if this approach was feasible and to measure the extent of their x-ray exposure. MATERIALS AND METHODS: After obtaining informed consent, we assigned a badge to each of 12 patients and used it for all brain imaging studies during their ICU stay. Cumulative dose was determined by quantifying exposure on the badge and correlating it with the number and type of examinations. RESULTS: The average skin dose for the 3 patients who had only diagnostic DSA without endovascular intervention was 0.4 Gy (0.2-0.6 Gy). The average skin dose of the 8 patients who had both diagnostic DSA and interventions (eg, intra-arterial treatment of vasospasm and coiling of aneurysms) was 0.9 Gy (1.8-0.4 Gy). One patient had only CT examinations. There was no effort made to include or exclude the badge in the working view during interventions. CONCLUSIONS: It is feasible to incorporate a film badge that uses a visual scale to monitor the x-ray dose into the care of hospitalized patients. Cumulative skin doses in excess of 1 Gy were not uncommon (3/12) in this group of patients with acute SAH. This approach could provide a measure of the cumulative dose and is a convenient tool to quantify the effect of dose-reduction strategies.

Endovascular treatment of unruptured intracranial aneurysms in the elderly: analysis of procedure related complications.

INTRODUCTION: The management of unruptured intracranial aneurysms in the elderly remains controversial. Treatment risks are thought to be higher in this group. Large series assessing endovascular treatment of unruptured intracranial aneurysms in the elderly are lacking. Our single center endovascular experience in treating unruptured intracranial aneurysms in the elderly is presented. METHODS: 77 patients, 70 years or older, were referred to the endovascular neurosurgery service for treatment of an unruptured intracranial aneurysm between February 2000 and May 2008. Hospital records, operative reports, angiograms and radiology reports were reviewed and analyzed retrospectively. RESULTS: 99 aneurysms were treated in 77 patients in 102 procedures. Mean patient age was 75±4 years, and the average aneurysm size was 11±7 mm. Adjuvant techniques were used in 66% of cases. Endovascular procedures included coiling alone (32%), balloon assisted coiling (19%), stent assisted coiling (37%), balloon assisted stent and coiling (8%), stent only (1%) and glue (2%). The permanent morbidity and mortality rates were 1% and 3%, respectively. Four adverse events were attributed to the patient's age. Posterior circulation aneurysms were associated with more adverse events (41%) than anterior circulation aneurysms (14%). Endovascular treatments using adjuvant techniques were associated with a higher complication rate than coiling alone. CONCLUSIONS: With only a 4% permanent rate of neurological morbidity and mortality, endovascular treatment of unruptured aneurysms can be performed safely in the elderly. Age should not be the limiting factor when considering endovascular therapy.

Successful treatment with voriconazole of Aspergillus brain abscess in a boy with medulloblastoma.

Invasive aspergillosis is an increasing problem in immuno-incompetent patients after prolonged steroid therapy, cancer radio-chemotherapy, and bone marrow or solid organ transplantation. Cerebral aspergillosis is a well-described complication of the invasive aspergillosis but only in rare cases, the brain is the sole site of infection. Despite increasing availability of antifungal drugs, the prognosis of cerebral aspergillosis is poor. We report on an 11-year-old boy with medulloblastoma in the area of the fourth ventricle. Following tumor surgery and radio-chemotherapy, several abscess-like structures occurred in the operating field. After incomplete abscess, resection histology and culture confirmed a localized Aspergillus fumigatus infection. The initial treatment of the Aspergillus fumigatus infection with conventional amphotericin B failed, and treatment with the triazole voriconazole was started. Intravenous treatment with voriconazole resulted in a reduction of the Aspergillus fumigatus abscess. After switching to oral ambulatory therapy, the Aspergillus fumigatus abscess increased in size. To improve treatment, voriconazole dosage was adapted to reach drug concentrations in cerebrospinal fluid (CSF) above the minimal fungicidal concentration and plasma specimens. During the concentration-controlled voriconazole therapy for a period of 18 months, a complete response was achieved.

[Pasteurella multocida as a rare cause of neonatal meningitis]. / Pasteurella multocida als seltener Erreger der neonatalen Meningitis.

Pasteurella multocida (P. multocida), a Gram-negative bacillus is a typical commensal in the oropharynx of animals such as dogs and cats. Human diseases caused by P. multocida are rare and include respiratory infections, sepsis and meningitis. P. multocida infections are described predominantly in patients with underlying chronic disorders, in elderly patients or in infants < or = 1 year. We describe the case of a 3-week-old boy with meningitis due to Pasteurella multocida. P. multocida was also identified in oral swab and stool cultures of the pet cat. A direct contact between baby and cat was negated by the parents. The patient recovered without any neurological sequelae.

Nutrition studies on protein and energy in domestic cats.

The effects of three diets varying in their protein, fat and carbohydrate contents and of physical activity on energy and protein metabolism were investigated in eight domestic cats. The diets were based on canned food with addition either of minced cattle heart, melted swine fat or polenta. The activity-induced heat production was measured in a respiration chamber using the Doppler effect of radio-waves reflected from moving bodies. In the group receiving the high-protein diet, urinary nitrogen concentration was higher which was reflected in higher urinary loss of energy without affecting the amount of energy retained. Nitrogen utilization was not significantly influenced by nitrogen intake. Mean daily total heat production ranged between 163 and 187 kJ/kg BW/day or 215 and 270 kJ/kg BW(0.75)/day. The daily crude protein requirement of adult cats was determined to be 2.7 g/kg BW/day. The daily requirement of metabolizable energy for maintenance was estimated to be 153 kJ/kg BW/day or 226 kJ/kg BW(0.75)/day. The activity-induced heat production was 25.1 kJ/kg BW/day which corresponded to 13.5% of the total daily heat production. The daily requirement for metabolizable energy was thus reduced by 20.9 kJ/kg BW/day or 13.7%. The activity pattern of the cats was not characterized by a circadian rhythm.

Deep cerebral venous sinus thrombosis often presents with neuropsychologic symptoms.

The outcome of cerebral venous sinus thrombosis (CVST) depends on rapid diagnosis and initiation of effective anticoagulation. We report seven cases of a subgroup with deep cerebral venous sinus thrombosis (DCVST) treated in our institution since 1990. Six of our seven patients presented with early neuropsychological deficits (mental obtundation, bradyphrenia or apathia). This clinical presentation, in combination with headache, and focal neurological deficits, aids the early diagnosis of DCVST. Thalamic hyperintensities on T2-weighted MRI images, previously considered infarctions, were fully reversible during treatment with heparin. This indicates that early in the course of the disease they correspond to vasogenic oedema.

Kaiser Permanente's "metadata-driven" national clinical intranet.

This paper describes the approach taken to build Kaiser Permanente's national clinical intranet. A primary objective for the site is to facilitate resource discovery, which is enabled by the use of "metadata", or data (fields and field values) that describe the various resources available. Users can perform full text queries and/or fielded searching against the metadata. Metadata serves as the organizing principle of the site--it is used to index documents, sort search results, and structure the site's table of contents. The site's use of metadata--what it is, how it is created, how it is applied to documents, how it is indexed, how it is presented to the user in the search and the search results interface, and how it is used to construct the table of contents for the web site--will be discussed in detail. The result is that KP's national clinical intranet has coupled the power of Internet-like full text search engines with the power of MedLine-like fielded searching in order to maximize search precision and recall. Organizing content on the site in accordance with the metadata promotes overall consistency. Issues currently under investigation include how to better exploit the power of the controlled terminology within the metadata; whether the value gained is worth the cost of collecting metadata; and how automatic classification algorithms might obviate the need for manual document indexing.