The impact of white matter lesions on the cognitive outcome of subthalamic nucleus deep brain stimulation in Parkinson's disease.

OBJECTIVES: White Matter lesions (WML) are a risk factor for cognitive impairment in Parkinson's disease. There is no clear evidence of reduced general cognitive function after DBS. However, a subgroup of patients develops dementia rapidly after DBS despite careful patient selection processes. The aim of this study was to evaluate the load of WML as a possible risk factor for cognitive decline following STN DBS. PATIENTS AND METHODS: 40 PD-patients receiving bilateral STN-DBS were followed at least three years after surgery to detect dementia. All patients underwent comprehensive neuropsychological assessment and MRI before surgery. The extent of WML was assessed using an automated approach. WML volume was correlated to the onset of dementia and the decline of a cognitive composite score retrospectively. RESULTS: Patients with a rapid onset of dementia within one, respective three following DBS showed significant higher WML volumes compared to cognitive normal and MCI patients (55.8cm3±18.836 vs. 9.3cm3±12.2; p=0.002). The same significant association was found in a multivariable model, including the covariables age, gender and PD disease duration (p=0.01). WML volume was associated to the rate of decline in cognitive composite score within three years after DBS surgery (p=0.006; R2=0.40) after correction for age. CONCLUSIONS: Damaged white matter may lead to a reduced compensation of disconnections in cognitive circuits caused by the implantation of the DBS electrodes or by chronic stimulation. The role of WML as a prognostic factor for the cognitive outcome after DBS may be underestimated. The WML burden should be taken seriously in preoperative risk stratification.

Single-crystal X-ray diffraction and resonant X-ray magnetic scattering at helium-3 temperatures in high magnetic fields at beamline P09 at PETRA III.

The resonant scattering and diffraction beamline P09 at PETRA III at DESY is equipped with a 14 T vertical field split-pair magnet. A helium-3 refrigerator is available that can be fitted inside the magnet's variable-temperature insert. Here the results of a series of experiments aimed at determining the beam conditions permitting operations with the He-3 insert are presented. By measuring the tetragonal-to-orthorhombic phase transition occurring at 2.1 K in the Jahn-Teller compound TmVO4, it is found that the photon flux at P09 must be attenuated down to 1.5 × 10(9) photons s(-1) for the sample to remain at temperatures below 800 mK. Despite such a reduction of the incident flux and the subsequent use of a Cu(111) analyzer, the resonant X-ray magnetic scattering signal at the Tm LIII absorption edge associated with the spin-density wave in TmNi2B2C below 1.5 K is intense enough to permit a complete study in magnetic field and at sub-Kelvin temperatures to be carried out.

A compact and low-weight sputtering unit for in situ investigations of thin film growth at synchrotron radiation beamlines.

In this work, we report on a highly variable, compact, and light high-vacuum sputter deposition unit designed for in situ experiments using synchrotron radiation facilities. The chamber can be mounted at various synchrotron beamlines for scattering experiments in grazing incidence geometry. The sample position and the large exit window allow to perform x-ray experiments up to large q values. The sputtering unit is easy to mount on existing experimental setups and can be remote-controlled. In this paper, we describe in detail the design and the performance of the new sputtering chamber and present the installation of the apparatus at different 3rd generation light sources. Furthermore, we describe the different measurement options and present some selected results. The unit has been successfully commissioned and is now available for users at PETRA III at DESY.

[Deep skin infection with Scedosporium apiospermum-infection in a renal transplant patient]. / Scedosporium-apiospermum-Infektion bei einem nierentransplantierten Patienten.

A 57-year-old immunosuppressed patient presented with multiple erythematous papules and pustules as well as isolated ulcerations on the right lower leg and subcutaneous nodules on the right thigh. The biopsy revealed granulomatous inflammation with numerous fungal hyphae, which were IDentified as Scedosporium apiospermum by PCR. He was treated with voriconazole 2 × 200 mg daily as well assurgical debridement. Scedosporium apiospermum is a rare pathogenic agent of deep mold fungus infections. Skin infections with Scedosporium apiospermum are underdiagnosed because of different clinical manifestations. In immunosuppressed patients, an infection represents a potentially life-threatening complication. Precise identification of the agent with introduction of antimycotic therapy appears to be pivotal to prevent fulminant disease.

[Guideline for antiretroviral therapy of HIV-infected children and adolescents]. / Leitlinie der Pädiatrische Arbeitsgemeinschaft AIDS (PAAD) e.V. zur antiretroviralen Therapie bei HIV-infizierten Kindern und Jugendlichen (2011).

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different. The above aspects and the decreased number of antiretroviral substances underline the need for specific guidelines for HIV-therapy in children and adolescents. The German Pediatric Working group AIDS (PAAD) has formulated this guideline in 2011 based on new study results, changes in international recommendations and newly available drugs.

Contained rupture of the aorta in acute Stanford type A aortic dissection causing right ventricular wall dissection.

We describe a rare case of an acute aortic type A dissection after previous aortic valve replacement and coronary artery revascularization complicated by a contained rupture and right ventricular wall dissection. Although preoperatively echocardiography and CT scan described a pericardial hematoma, intraoperatively no intrapericardial hematoma was found; instead an extended right ventricular wall dissection caused by a large thrombus formation within the right ventricular muscle layers was demonstrated. After replacement of the ascending aorta and removal of the thrombus as the sole treatment for right ventricular wall dissection, the two dissected layers of the right ventricular wall were contracting synchronously again.

Can elderly patients with colorectal cancer tolerate planned surgical treatment? A practical approach to a common dilemma.

AIM: Analysing the effectiveness of a surgical procedure is mandatory in every modern health-care system. The aging of the population stresses the need for a good standard of care. This study tests the hypothesis that porthsmouth-physiologic operative severity score for enumeration of morbidity and mortality (P-POSSUM) and colorectal-POSSUM (CR-POSSUM) would be useful clinical auditing tools in colorectal cancer surgery for aged patients. METHOD: One hundred and seventy-seven consecutive patients over 70 years of age underwent emergency or elective surgery from January 2003 to December 2005. Demographic, clinical and surgical information, score systems' prediction, complications and 30-day mortality data were prospectively entered in a comprehensive database. The observed over expected morbidity and mortality rate was calculated. RESULTS: Thirty-day observed mortality was 10.3% (19/177) while P-POSSUM and CR-POSSUM expected mortality were, respectively, 11.21% (P = NS) and 13.08% (P = NS). Overall observed morbidity was 42.7%, P-POSSUM prediction was 59.3% (P = 0.002). Morbidity and mortality data were analysed for specific subgroups of patients (resection and anastomosis/resection and stoma/palliative; emergency/elective). CONCLUSION: P-POSSUM and CR-POSSUM are useful tools to predict mortality in elderly patients. P-POSSUM significantly overestimated the risk of complications. A more accurate tool for preoperative assessment for aged patients is probably needed to predict the post-surgical outcome.

No association of the CD45 77C>G transversion with inflammatory bowel disease in German patients.

A 77C>G transversion in exon A of the CD45 gene was investigated in patients with inflammatory bowel disease (IBD) and controls. The distribution of the 77G allele was not significantly different between patients and controls. We found no evidence for the contribution of the 77C>G transversion in susceptibility to IBD.

Phosphorylation at Ser244 by CK1 determines nuclear localization and substrate targeting of PKD2.

Protein kinase D2 (PKD2), a member of the PKD family of serine/threonine kinases, is localized in various subcellular compartments including the nucleus where the kinase accumulates upon activation of G-protein-coupled receptors. We define three critical post-translational modifications required for nuclear accumulation of PKD2 in response to activation of the CCK2 receptor (CCK2R): phosphorylation at Ser706 and Ser710 within the activation loop by PKC eta leading to catalytic activity and phosphorylation at Ser244 within the zinc-finger domain, which is crucial for blocking nuclear export of active PKD2 by preventing its interaction with the Crm-1 export machinery. We identify CK1delta and epsilon as upstream activated kinases by CCK2R that phosphorylate PKD2 at Ser244. Moreover, nuclear accumulation of active PKD2 is a prerequisite for efficient phosphorylation of its nuclear substrate, HDAC7. Only nuclear, active PKD2 mediates CCK2R-induced HDAC7 phosphorylation and Nur77 expression. Thus, we define a novel, compartment-specific signal transduction pathway downstream of CCK2R that phosphorylates PKD2 at three specific sites, results in nuclear accumulation of the active kinase and culminates in efficient phosphorylation of nuclear PKD2 substrates in human gastric cancer cells.

Assuming exponential decay by incorporating viscous damping improves the prediction of the coefficient of friction in pendulum tests of whole articular joints.

A pendulum test with a whole articular joint serving as the fulcrum is commonly used to measure the bulk coefficient of friction (COF). In such tests it is universally assumed that energy loss is due to frictional damping only, and accordingly the decay of pendulum amplitude is linear with time. The purpose of this work was to determine whether the measurement of the COF is improved when viscous damping and exponential decay of pendulum amplitude are incorporated into a lumped-parameter model. Various pendulum models with a range of values for COF and for viscous damping were constructed. The resulting decay was fitted with an exponential function (including both frictional and viscous damping) and with a linear decay function (frictional damping only). The values predicted from the fit of each function were then compared to the known values. It was found that the exponential decay function was able to predict the COF values within 2 per cent error. This error increased for models in which the damping coefficient was relatively small and the COF was relatively large. On the other hand, the linear decay function resulted in large errors in the prediction of the COF, even for small values of viscous damping. The exponential decay function including both frictional and constant viscous damping presented herein dramatically increased the accuracy of measuring the COF in a pendulum test of modelled whole articular joints.

Surgical repair of the aortic coarctation combined with complete replacement of the ascending aorta and aortic arch.

We present a 63-year-old patient with aortic valve stenosis, ascending aorta aneurysm, aortic coarctation as well as atherosclerotic, elongated, and stenosed aortic arch. Surgical treatment consisted of a complete ascending aorta replacement with a valved composite graft and complete replacement of the aortic arch including the isthmus, and was performed simultaneously through median sternotomy.

Relative value of sliding-thin-slab multiplanar reformations and sliding-thin-slab maximum intensity projections as reformatting techniques in multisection CT angiography of the cervicocranial vessels.

BACKGROUND AND PURPOSE: To investigate image quality and vascular delineation of multisection CT (MSCT) angiography of the cervicocranial vessels with sliding-thin-slab (STS) maximum intensity projections (MIP) and multiplanar reformations (MPR). MATERIALS AND METHODS: Ten patients examined with a standardized protocol on a 16-section MSCT were included in the study. The data were reformatted as MIP and MPR in 3 planes for each subject; both reformatting techniques were applied in an STS technique with an increment of 3 mm. Images were evaluated independently by 3 blinded readers grading image quality parameters and vascular delineation of supra-aortic arteries and veins. An extension of the Mantel-Haenzel row mean score test was used to compare the distribution of scores for vascular delineation and image quality between STS MIP and STS MPR. RESULTS: STS MIP reformations were significantly superior to STS MPR in the delineation of all extra- and intracranial arteries and arterial segments and in the delineation of the cavernous sinus and the internal cerebral veins (P < .05). No significant differences were found for the large venous vessels, the visual assessment of vascular contrast, or the impact of imaging artifacts. CONCLUSION: Because STS MIP reformations were preferred to or equal to STS MPR in all aspects, we recommend STS MIP as the primary reformatting technique in MSCT angiography of the cervicocranial vessels in addition to viewing the source images.

[Comparison of biphasic spiral CT and MnDPDP-enhanced MRI in the detection and characterization of liver lesions]. / Vergleich von Doppel-Spiral-CT und MnDPDP-verstärkter MRT zur Erfassung und Charakterisierung von Leberläsionen.

INTRODUCTION: To evaluate the efficacy of biphasic spiral CT and MnDPDP (Teslascan, Nycomed Amersham) enhanced MR imaging to detect and classify liver lesions. MATERIALS AND METHODS: 39 patients with known or suspected liver lesions were included into this study and examined with biphasic spiral CT and MnDPDP-enhanced MRI. 25 histological reports and 1 extreme increased serum AFP value could be obtained from 22 patients, therefore only these 26 proven lesions were included into this analysis. RESULTS: From 39 patients CT revealed in 54% (14 lesions) and MRI in 54% correct (i.e., corresponding to the histology) diagnosis. Correct CT/wrong MRT diagnosis and vice versa was present in only 2 lesions each. Differentiating into benign versus malignant lesion was successful in 73% for MRI and 77% for CT. In 81% MRI revealed the correct type of lesion (hepatocellular or non-hepatocellular) vs. 77% with CT. Sensitivity/specificity for differentiation into benign/malignant lesions was 86%/70% (MRI) and 87%/77% (CT) and for differentiation of the lesions origin 100%/80% (MRI) and 80%/75% (CT), these differences were not significant. MnDPDP-enhanced MRI showed significantly more lesions than non-enhanced MRI. CONCLUSION: MnDPDP-enhanced MRI is better than CT in differentiating hepatocellular liver lesions from non-hepatocellular lesions. After contrast enhancement with MnDPDP significantly more lesions could be evaluated in MRI. MnDPDP improves, in combination with biphasic helical CT, the diagnosis of liver lesions.

Clinical predictors of endometritis in women with symptoms and signs of pelvic inflammatory disease.

OBJECTIVE: Careful detection and treatment of pelvic inflammatory disease are essential for the prevention of adverse sequelae. The purpose of this study was to evaluate the diagnostic test characteristics of clinical criteria for the diagnosis of pelvic inflammatory disease. STUDY DESIGN: We performed a cross-sectional analysis of the baseline characteristics of 651 patients enrolled in a multicenter randomized treatment trial for pelvic inflammatory disease. Clinical and laboratory findings were recorded for all patients, and endometrial sampling was performed. We calculated sensitivity and specificity and performed receiver operating characteristic curve analysis and multivariate logistic regression, using histologic endometritis as the criterion standard. RESULTS: The minimal criteria for pelvic inflammatory disease, as recommended by the Centers for Disease Control and Prevention, had a sensitivity of 83%, in comparison with a 95% sensitivity for adnexal tenderness (P =.001). Of the supportive clinical criteria, the finding most highly associated with endometritis was a positive test result for Chlamydia trachomatis or Neisseria gonorrhoeae (adjusted odds ratio, 4.3; 95% confidence interval, 2.89--6.63). A multivariate logistic regression model indicated that combinations of criteria significantly improve the prediction of endometritis. CONCLUSION: Sensitivity can be maximized by using the presence of adnexal tenderness as a minimal criterion for the diagnosis of pelvic inflammatory disease, and supportive criteria are helpful in estimating the probability of endometritis.

Heterologously expressed inner lipoyl domain of dihydrolipoyl acetyltransferase inhibits ATP-dependent inactivation of pyruvate dehydrogenase complex. Identification of important amino acid residues.

The activity of the pyruvate dehydrogenase multienzyme complex (PDC), which catalyses the oxidation of pyruvate to acetyl-CoA within the mitochondrion, is diminished in animal models of diabetes. Studies with purified PDC components have suggested that the kinases responsible for inactivating the decarboxylase catalytic subunits of the complex are most efficient in their regulatory role when they are bound to dihydrolipoyl acetyltransferase (E2) subunits, which form the structural core of the complex. We report that the addition of an exogenous E2 subdomain (inner lipoyl domain) to an intact PDC inhibits ATP-dependent inactivation of the complex. By combining molecular modelling, site-directed mutagenesis and biophysical characterizations, we have also identified two amino acid residues in this subdomain (Ile229 and Phe231) that largely determine the magnitude of this effect.

[Spiral computed tomography for treatment planning and quality assurance in radiotherapy]. / Spiralcomputertomographie zur Bestrahlungsplanung und Qualitätssicherung in der Strahlentherapie.

BACKGROUND: The possibilities of spiral CT for radiotherapeutic treatment planning and quality assurance have been systematically investigated. PATIENTS AND METHODS: The influence of parameters such as slice thickness, table speed and increment on geometric accuracy was studied. Ring-, spheric-, PMMA- and humanoid Alderson phantoms were used. Furthermore, patients with infradiaphragmatic irradiation of Hodgkin's disease or with mediastinal irradiation were studied using CT-angiography. Patients with carcinomas of the head and neck before HDR- and PDR-brachytherapy were examined as well. RESULTS: Spiral CT offers 3D volume data information with excellent reduction of breath and motion artefacts for virtual simulation. 2D multiplanar reconstructions with excellent local resolution may be obtained. 3D MIP (Maximum Intensity Projection), based on CT-angiographic imaging, is a good tool for infradiaphragmatic treatment planning of Hodgkin's disease, if small numbers for slice thickness, table speed and increment are used. SSD (Surface Shaded Display) offers good 3D visualization and good geometric control of intracavitary and interstitial brachytherapy applicators. High qualitative multiplanar reconstructions are useful for CT-based brachytherapy planning. CONCLUSIONS: Spiral CT is a precious tool for 3D treatment planning and virtual simulation in radiotherapy and superior to conventional CT data acquisition. Quality assurance is improved for dose-volume-histograms and for brachytherapy.

[Placebo-controlled double-blind study of the effectiveness of Ginkgo biloba special extract EGb 761 in trained patients with intermittent claudication]. / Placebokontrollierte Doppelblindstudie zur Wirksamkeit von Ginkgo-biloba-Spezialextrakt EGb 761 bei austrainierten Patienten mit Claudicatio intermittens.

This monocenter, randomized, placebo-controlled double-blind study with parallel-group comparison was carried out in order to demonstrate the efficacy of Ginkgo biloba special extract EGb 761 on objective and subjective parameters of the walking performance in trained patients suffering from peripheral arterial occlusive disease in Fontaine stage IIb. In total 60 patients were recruited (42 men; aged 47-82 years) with angiographically proven peripheral arterial occlusive disease of the lower extremities and an intermittent claudication existing for at least 6 months. No improvement had been shown despite consistent walking training and a maximum pain-free walking distance on the treadmill of less than 150 m was recorded at the beginning of the study. The therapeutic groups were treated with either Ginkgo biloba special extract EGb 761 at a dose of 3 times 1 film-coated tablet of 40 mg per day by oral route or placebo over a duration of 24 weeks following a two-week placebo run-in phase. The main outcome measure was the difference of the walking distance between the start of treatment and after 8, 16 and 24 weeks of treatment as measured on the treadmill (walking speed 3 km/h and slope of 12%). As secondary parameters the corresponding differences for the maximum walking distance, the relative increase of the pain-free walking distance, the Doppler index and the subjective evaluation of the patients were analyzed. The absolute changes in the pain-free walking distance in treatment weeks 8, 16 and 24 as against the treatment beginning (median values with 95% confidence interval) led to the following values for the patients treated with Ginkgo biloba special extract EGb 761:19 m (14, 33), 34 m (18, 50) and 41 m (26, 64). The corresponding values in the placebo group were as follows: 7 m (-4, 12), 12 m (5, 22) and 8 m (-1, 21). The advantage of the EGb 761-treated group as compared to the placebo group could be verified statistically at the 3 time points with p < 0.0001, p = 0.0003 and p < 0.0001. The test for the presence of a clinically relevant difference of 20% between EGb 761 and placebo also produced a statistically significant result (p = 0.008). The Doppler index remained unchanged in both therapeutic groups: A corresponding statistically significant advantage for the EGb 761 group was observed on a descriptive level for the other parameters tested. The tolerance of the treatment was very good. The results of this placebo-controlled study show that treatment with Ginkgo biloba special extract EGb 761 produces a statistically highly significant and clinically relevant improvement of the walking performance in trained patients suffering from intermittent claudication with very good tolerance of the study preparation.

AT-rich upstream sequence elements regulate spore germination-specific expression of the Dictyostelium discoideum celA gene.

Two members of a family of spore germination-specific cDNAs, celA and celB, are expressed coordinately, exclusively during spore germination. In the present study the regulatory sequence elements responsible for celA germination-specific expression have been identified. The very AT-rich 81 bp sequence between -664 and -584 upstream of the translation initiation site was required for proper temporal transcription of the celA gene. This sequence is comprised of two cis elements, each of which was active by itself in allowing celA expression. Electrophoretic mobility shift assays showed that a factor(s) in an extract prepared from germinating spores bound to the celA regulatory region. One of the three complexes formed was specific for the germinating spore extract. The results are consistent with the notion that the factor(s) that binds to this regulatory region is involved in expression of celA.