Long-term follow-up and quality of life in patients with intracranial germinoma.

Intracranial germinomas are fairly rare tumors occurring mostly in children or young adults with a comparatively good prognosis. Radiation is the preferred treatment of choice for this diagnosis. It has been thoroughly studied to what extent radiation doses and fields can be limited in order to avoid side effects in these young patients. The role of chemotherapy remains unclear, whereas surgery is limited to biopsy for proof of histology. Regarding the good overall survival rate, quality of life is a significant aspect to consider in these patients. We present a single institution analysis of patients with intracranial germinoma and analyze the long-term outcome with special regard to quality of life. Thirty-three patients with intracranial germinomas were analyzed by chart review, telephone interview, and neurological assessment. Additionally, a survey on quality of life was performed. The 10-year overall survival rate was 82.1 % at a mean follow-up of 141 (22-306) months. Three quarters (76 %) of the patients reached a favorable neurological outcome on the Modified Rankin Scale (mRS 0-2). However, the self-reported quality of life was significantly worse in germinoma patients compared with a healthy control group (p < 0.001). Surgical resection of the tumor led to no improvement regarding overall survival, neurological outcome, and quality of life. In terms of cognitive functioning, patients with tumor resection were significantly more impaired than biopsied patients (p = 0.04). Although germinomas are efficiently treatable tumors, the restrictions in quality of life in these often young patients are considerable, including financial difficulties. There seems no justification for tumor resection in newly diagnosed cases suspicious for germinoma as the cognitive outcome is worse than in biopsied patients, and there is no effect on overall survival.

Meso-Rex shunt using deep femoral vein conduit: first report.

The Meso-Rex shunt (MRS) procedure was first described in 1992 by de VILLE et al. for the treatment of extrahepatic portal vein obstruction (EHPVO) in paediatric liver transplant patients. This technique provides more physiological relief of portal hypertension compared to the porto-systemic shunts, which can lead to long-term complications such as hyperammonaemia and hepato-pulmonary syndrome. Different conduits as autologous and cryopreserved veins or prosthetic grafts have been previously reported. We present herein the first case of a MRS using the autologous deep femoral vein in a 17-year-old female patient affected by EHPVO from unknown reasons.

Skeletal spread of an anaplastic astrocytoma (WHO grade III) and preservation of histopathological properties within metastases.

BACKGROUND: The incidence of extraneural metastases of glioma is low. Metastases occur at different sites and, infrequently, as diffuse bone marrow infiltration. Direct contact of a glioma with extrameningeal tissues might be a reason for extraneural metastases. However, the role of haematogenous spread remains unclear. METHODS: We report on a young patient who suffered from a left frontal anaplastic WHO grade III astrocytoma, which was treated with gross total resection and irradiation (60 Gy). No local relapse occurred during the following course, but a diffuse infiltration of the bone marrow was diagnosed 12 months after the initial diagnosis. The patient died 6 months later, as a result of hypercalcaemia and pancytopenia. The histopathological properties of the tumour and its bone metastases were analysed, as well as the mutations of the isocitrate dehydrogenase 1 gene (IDH1). To study the route of tumour dissemination, the peripheral blood of the patient was analysed for circulating tumour cells (CTCs). RESULTS: This study describes a rare case of an extraneurally metastasised WHO grade III anaplastic astrocytoma. The occurrence of bone marrow infiltration coinciding with the finding of a stable intracranial tumour is a notably unusual situation. The properties of the primary tumour were maintained within the metastases in our patient. No CTCs were found in the peripheral blood at one random time point after the diagnosis of bone metastases. CONCLUSIONS: Despite young patient age, a stable intracranial course with a single location and mutations in the IDH1 gene, the patient's overall survival was short at 18 months after diagnosis. This finding illustrates the therapeutic dilemma in patients with bone marrow involvement complicating the use of alkylating agents, such as temozolomide. Repeated and systematic blood sampling in a large cohort of patients is needed for the detection of CTCs in glioma patients with systemic tumour spread. Future studies investigating how intrinsic factors in glioma cell biology cause rare metastases in these tumours are needed.

Impact of protein content on proton diffusibility in intracranial cysts.

PURPOSE: The physical background of diffusion phenomena in intracranial cysts is unclear in some cases. To evaluate a potential dependency of proton diffusion on the concentration of proteins in cystic lesions we investigated the correlation of diffusion weighted imaging (DWI) and magnetization transfer ratio imaging (MTR) in intracranial cystic pathologies in vivo and in vitro with protein solutions. MATERIALS AND METHODS: 21 patients (14 male/7 female) with intracranial cystic lesions underwent preoperative MRI (1.5T) including MTR and DWI sequences. For comparison a series of samples with declining concentration of albumin was investigated in vitro with a 7T animal scanner. RESULTS: In the patients examination mean ADC values were 1.93×10-3mm2/sec and mean MTR values were 0.2. Mean ADC value of the albumin solutions was 0.22× 0-3mm2/sec and mean MTR was 0.12. ADC and MTR values showed a strong negative correlation in the patients (Spearman's rank correlation rs=-0.80, p<0.01) and a very strong negative correlation in the in vitro examinations (rs=-1.0, p<0.01). CONCLUSION: The strong negative correlation of ADC and MTR values suggest a strong influence of proteins on proton diffusion in intracranial cysts. The phenomena can be explained by macromolecules that bind nearby protons in their vicinity.

Enteroliths in Crohn's disease: a case report.

Bowel wall inflammation in Crohn's disease can be the cause of strictures along the small and large bowel. Frequently there is an accompanying prestenotic bowel dilation. This creates stasis of bowel fluids, which can eventually lead to the formation of enteroliths. These are hard dense masses inside the bowel that may be responsible for (sub)obstruction, ulceration and even perforation. The latter is caused by mechanical stress on an already weak and inflamed bowel wall. We present a rare case of a Crohn's disease patient in her early thirties who was seen at the emergency department with acute abdominal pain. Radiographs and CT examination showed the appearance of enterolithiasis. Furthermore, we provide diagnostic and therapeutic options.

The anterolateral thigh flap for complicated abdominal wall reconstruction after giant incisional hernia repair.

In the management of giant incisional hernias with loss of domain several surgical obstacles have to be addressed. Adequate coverage of the defect using mesh, sufficient local tissue advancement and prevention of wound and mesh infections are prerequisites for success. We present a case of a complicated giant incisional hernia repair after oncologic surgery, in which we chose for an intraabdominal mesh repair using a composite mesh. The patient developed a wound dehiscence and mesh infection, successfully treated with negative pressure therapy followed by a free ALT perforator flap. Several surgical techniques are discussed to manage these complicated hernias, such as progressive pneumoperitoneum, the component separation technique and the importance of soft tissue coverage (e.g. anterolateral thigh flap). In cases of wound complications, negative pressure therapy and new soft tissue coverage are discussed.

Treatment of symptomatic mobile aortic thrombus.

BACKGROUND: Mobile thoracic or abdominal aortic thrombi are a potential source of embolism to visceral organs or lower limbs. Detection levels of this type of aortic pathology after any embolic event have increased considerably. Nevertheless, therapeutic management of an intraluminal mobile thrombus of the aorta remains controversial. The aim of this study is to describe the treatment modalities for symptomatic mural aortic thrombi based on three cases diagnosed at our institution and to review the literature. METHODS: During the last decade, several patients with peripheral embolisation were diagnosed with an intraluminal mobile aortic thrombus. Three patients who were treated differently were selected and reviewed. In addition a literature search was performed on PubMed and Medline from their inception to the present for all English language articles using the following keywords: blue toe syndrome, peripheral arterial embolisation, mobile thrombus and aorta. The advantages and drawbacks of medical management, open and endovascular treatment are described. RESULTS: Three particular patients with embolisation due to a floating aortic thrombus were reviewed. The first patient underwent a thoracotomy with replacement of the descending thoracic aorta. Another case was treated successfully by implanting an endovascular stent graft in the descending thoracic aorta. The last patient was treated medically because of the involvement of the visceral vessels. When reviewing the literature, no randomised controlled trials were found but several case reports have described both open and endovascular techniques. No long-term follow up of this rare pathology is available. CONCLUSIONS: In the literature there is no consensus how to treat a symptomatic floating aortic thrombus. This report shows that therapeutic strategies are influenced by the localisation of the thrombus, the co-morbidities of the patient and the physician' s preferences. Endovascular treatment in combination with high dose statins has become the preferred treatment method although long-term data are lacking.

Intracranial aneurysms in childhood: report of 8 cases and review of the literature.

OBJECTIVE: Subarachnoid haemorrhage (SAH) due to ruptured cerebral aneurysms is a rare diagnosis in childhood and is believed to differ from that in adults with regard to sex, aneurysm size and location, clinical appearance as well as outcome, suggesting that aneurysms in childhood are a distinct entity. PATIENTS AND METHODS: Seven children and young adults with a mean age of 13.6 years suffered from aneurysmal subarachnoid haemorrhage. On admission two patients were Hunt & Hess (HH) grade I, four were grade III and one was grade V. In addition, there was one 14-year-old boy who presented with seizures and was found to have a non-ruptured aneurysm of the basilar tip. Overall, there were two female and six male patients. Anterior circulation aneurysms were diagnosed in five patients whereas three patients suffered from posterior circulation aneurysm. Five large (10-25 mm) aneurysms and three smaller than 10 mm were found. Surgical clipping of the aneurysms was performed in all patients. RESULTS: Six patients showed no significant disability or no symptoms at all when evaluated with the modified Rankin Scale (mRS 0 or 1). One patient suffered from persisting nerve palsies (mRS 2) and one 6-year-old boy, admitted with HH grade V, died due to the initial poor clinical condition followed by severe brain oedema and secondary complications. CONCLUSIONS: Reviewing the literature, a male predominance, low rate of SAH, high percentage of complex aneurysms and of aneurysms located in the posterior circulation are characteristic features of aneurysms in childhood. Once a cerebral aneurysm is diagnosed in the younger age group, definite therapy should be performed soon as the outcome is expected to be more favourable than in adulthood.

Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines.

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.

Deficiency of regulatory B cells increases allergic airway inflammation.

OBJECTIVE: To investigate the effect of the X-linked immunodeficiency (Xid) B cell defect on the response to the cockroach allergen in mice. METHODS: Two cockroach allergen immunization and challenge protocols were employed to sensitize CBA/J wild-type and CBA/CaHN-btk(-/-)xid/J (Xid) mice. Blood and tissue samples were collected 24 and 48 hrs after the last intratracheal antigen challenge and were analyzed for several parameters of allergic inflammation. RESULTS: Nearly equivalent amounts of serum IgE were detected in Xid and CBA/J mice after short-term antigen challenge despite the B cell deficiency in Xid mice. A decreased concentration of IgE was detected in CBA/J mice after repeated allergen challenges but not in the Xid mice. Correlating with the discrepancy in serum IgE levels, higher levels of IL-13, IL-5, IL-10 and CCL5 were measured in whole lung homogenates from allergen-challenged Xid mice compared to CBA/J mice. In addition, draining lymph node cells from Xid mice expressed elevated levels of IL-4, IL-5, IL-10 and IFNgamma mRNA compared to cells from CBA/J mice after in vitro culture with cockroach antigen. An increase in lung inflammation, interstitial eosinophilia and mucus production was also observed in allergen-challenged Xid mice. CD95L expression increased on B-1a cells following allergen challenge, which was accompanied by an increase in lung CD4(+) Th cell apoptosis in wild-type CBA/J mice. In contrast, Xid mice did not have an increase in CD4(+) T cell apoptosis following allergen challenge. CONCLUSIONS: These data suggest a regulatory role for B-1a cells in reducing cytokine production, pulmonary inflammation, and CD4(+) T cell survival during cockroach allergen-induced airway inflammation.

Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration.

The primary cardiac response to ischemic insult is cardiomyocyte hypertrophy, which initiates a genetic program culminating in apoptotic myocyte loss, progressive collagen replacement, and heart failure, a process termed cardiac remodeling. Although a few cardiomyocytes at the peri-infarct region can proliferate and regenerate after injury, no approaches are known to effectively induce endogenous cardiomyocytes to enter the cell cycle. We recently isolated, in human adult bone marrow, endothelial progenitor cells, or angioblasts, that migrate to ischemic myocardium, where they induce neovascularization and prevent myocardial remodeling. Here we show that increasing the number of angioblasts trafficking to the infarct zone results in dose-dependent neovascularization with development of progressively larger-sized capillaries. This results in sustained improvement in cardiac function by mechanisms involving protection against apoptosis and, strikingly, induction of proliferation/regeneration of endogenous cardiomyocytes. Our results suggest that agents that increase myocardial homing of bone marrow angioblasts could effectively induce endogenous cardiomyocytes to enter the cell cycle and improve functional cardiac recovery.

Anodic oxidation of ifosfamide and cyclophosphamide: a biomimetic metabolism model of the oxazaphosphorinane anticancer drugs.

The electrochemical oxidation of anticancer drugs ifosfamide and cyclophosphamide produced in high yield methoxylated analogues of the key hydroxy-metabolites of these oxazaphosphorine prodrugs. The cytotoxicity of these compounds was evaluated, and found to be as high as the hydroxy-metabolite.

Early Permian bipedal reptile.

A 290-million-year-old reptilian skeleton from the Lower Permian (Asselian) of Germany provides evidence of abilities for cursorial bipedal locomotion, employing a parasagittal digitigrade posture. The skeleton is of a small bolosaurid, Eudibamus cursoris, gen. et sp. nov. and confirms the widespread distribution of Bolosauridae across Laurasia during this early stage of amniote evolution. E. cursoris is the oldest known representative of Parareptilia, a major clade of reptiles.

Influence of continuous veno-venous haemodiafiltration and continuous veno-venous haemofiltration on the pharmacokinetics of fluconazole.

OBJECTIVE: To compare the elimination of fluconazole by continuous veno-venous haemodiafiltration (CVVHD) and continuous veno-venous haemofiltration (CVVH) at different dosages. INTERVENTION: Patients received doses of 400 mg (n=3), 600 mg (n=1) or 800 mg (n=2) fluconazole as a short-time infusion once a day. Patients underwent CVVHD the first day and CVVH the second day. CVVHD and CVVH were performed using an acrylonitrile hollow-fibre filter at a constant blood flow of 90 ml/min and a substitution flow of 1000 ml/h (predilution). During CVVHD, the dialysate flow was 1000 ml/h. Ultrafiltration rates were 1158+/-90.5 ml/h during CVVHD and 1167+/-81.6 ml/h. Serum and ultrafiltrate/dialysate concentrations of fluconazole were determined on nine occasions over 24 h. PARTICIPANTS: Six critically ill patients with acute renal failure (ARF) and serious fungal infection. RESULTS: Extracorporeal clearance (CVVHD 30.5+/-6.0 ml/min, CVVH 17.5+/-4.0 ml/min) and total clearance of fluconazole (CVVHD 37.9+/-4.4 ml/min, CVVH 25.3+/-6.5 ml/min) were significantly higher during CVVHD (P < 0.05). During CVVHD, the sieving coefficient (S(CVVHD)) was 0.88 (range 0.54-1) and the elimination half-life (t1/2) was 14.8-35.1 h. During CVVH, the S(CVVH) was 0.96 (range 0.56-1.02) and t1/2 was 24.0-51.6 h. CONCLUSIONS: A daily dosage of 400-800 mg fluconazole is recommended in the treatment of life-threatening fungal infections in critically ill patients undergoing CVVHD since the clearance of CVVHD may considerably exceed the clearance in patients with normal renal function, which is about 20 ml/min. Drug monitoring is highly recommended for these patients.

[The relationship between the perceived threat of environmental problems and the formation of action intentions]. / Der Zusammenhang von wahrgenommener Bedrohung durch Umweltgefahren und der Ausbildung von Handlungsintentionen.

The results of a study using questionnaires at two measuring points in high schools in North Germany are reported and discussed. This article analyzes the students' reasons and motivation for more or less environmentally friendly behavior. An integrated theoretical concept of motivation for human action formed the theoretical basis. The action genesis process was subdivided into the phases of forming motives, intentions and volition. Following a presentation of this theoretical concept and its definition with regard to competing and compatible theoretical hypotheses, the methodological procedure is described whereby the various motivation structures of the pupils questioned were analyzed. Mixed distribution models were used which allow modelling of complex multivariate relationships (latent class analysis and mixed Rasch models). The results show strong positive relationships among the variables of the motivation, the intention and the volition phases, but with isolated area-specific motivation patterns and moderator effects of certain cognitive variables.

An in vitro osteotomy method to expose the medial compartment of the human knee.

This study was conducted to validate a new in vitro method to expose the medial compartment of the knee to be used in subsequent studies aimed at examining the load bearing capabilities of medial meniscal allografts. The new method involves an osteotomy and reattachment of the medial femoral condyle. The primary hypothesis was that the new method does not alter tibio-femoral contact pressure and area. To validate this method, the baseline contact pressure of the intact medial compartment was measured using a new nondestructive procedure for inserting pressure measurement film into the intact medial hemijoint. A secondary and related hypothesis was that incising the coronary ligament, a destructive method used by previous investigators to position pressure measurement film, alters the normal tibio-femoral contact pressure. To test these hypotheses, Fuji Prescale pressure-sensitive film was used to measure both tibio-femoral contact pressure and area within the medial compartment of the (1) intact knee, (2) the knee after osteotomizing and reattaching the medial femoral condyle, and (3) the osteotomized knee with an incised coronary ligament, using seven cadaver specimens. Measurements were taken at a compressive load of approximately two times body weight with the knee in 0, 15, 30, 45 deg of flexion. No significant differences between the intact and osteotomized knee were detected. Likewise, no significant differences were observed between the osteotomized knee and the osteotomized knee with an incised coronary ligament. These results confirm the utility of the new method in exposing the medial compartment for manipulation and placement of medial meniscal allografts in future studies examining the load-bearing characteristics of meniscal allografts.

Predictive microbiology in a dynamic environment: a system theory approach.

The main factors influencing the microbial stability of chilled prepared food products for which there is an increased consumer interest-are temperature, pH, and water activity. Unlike the pH and the water activity, the temperature may vary extensively throughout the complete production and distribution chain. The shelf life of this kind of foods is usually limited due to spoilage by common microorganisms, and the increased risk for food pathogens. In predicting the shelf life, mathematical models are a powerful tool to increase the insight in the different subprocesses and their interactions. However, the predictive value of the sigmoidal functions reported in the literature to describe a bacterial growth curve as an explicit function of time is only guaranteed at a constant temperature within the temperature range of microbial growth. As a result, they are less appropriate in optimization studies of a whole production and distribution chain. In this paper a more general modeling approach, inspired by system theory concepts, is presented if for instance time varying temperature profiles are to be taken into account. As a case study, we discuss a recently proposed dynamic model to predict microbial growth and inactivation under time varying temperature conditions from a system theory point of view. Further, the validity of this methodology is illustrated with experimental data of Brochothrix thermosphacta and Lactobacillus plantarum. Finally, we propose some possible refinements of this model inspired by experimental results.

Safety aspects of "sous vide" products and prevention of microbial risks.

The diversity and quantities of vacuum packed and vacuum cooked prepared meals and menu components are rapidly growing on the European market. Because of the minimal heat processing, high water activity, absence of preservatives, and the use of many different often exotic ingredients, these products have a high risk potential. For this reason, Anglo-Saxon governments and industries are very sceptical about the safety of "sous vide" products. Industrial practice, as well as parallel tests and recent studies on inoculated packs have shown that, in many cases, it is more a potential than a real risk. Quality is the primary concern for "sous vide" products, and safety must be guaranteed by the application of the Hazard Analysis Critical Control Point (HACCP) concept, along with an adequate combination of different inhibitory factors (temperature of heating and cooling, pH, incorporation of starter cultures, bacteriocins and some particular enzymes).

Computer aided microbial safety design of food processes.

To reduce the time required for product development, to avoid expensive experimental tests, and to quantify safety risks for fresh products and the consequence of processing there is a growing interest in computer aided food process design. This paper discusses the application of hybrid object-oriented and rule-based expert system technology to represent the data and knowledge of microbial experts and food engineers. Finite element models for heat transfer calculation routines, microbial growth and inactivation models and texture kinetics are combined with food composition data, thermophysical properties, process steps and expert knowledge on type and quantity of microbial contamination. A prototype system has been developed to evaluate changes in food composition, process steps and process parameters on microbiological safety and textual quality of foods.

Ditiocarb: decomposition in aqueous solution and effect of the volatile product on its pharmacological use.

The kinetic profile for the decomposition of ditiocarb sodium salt in aqueous solution was achieved with UV-visible absorption spectrometry. The kinetic profile indicates that the decomposition reaction is hydrogen ion-catalyzed over the entire 4-10 pH range and enables the determination of the value of the acid-base equilibrium constant (Ka = 4.0.10(-4) at 5 degrees C). Decomposition of ditiocarb produces volatile carbon disulfide, exclusive of hydrogen sulfide, as shown with electrochemical methods. This feature is of interest from a toxicological point of view.