Evidence of ochratoxin A conjugates in urine samples from infants and adults.

Ochratoxin A (OTA), a mycotoxin with nephrotoxic and carcinogenic properties, is an important contaminant of food and feed. Analysis of OTA in human biological fluids (blood, urine, or breast milk) has documented frequent exposure to this mycotoxin, yet at quite variable levels in different population groups across the world. Urine is the preferred matrix in biomonitoring since sample collection is non-invasive and better accepted by study participants. As only a small fraction of the ingested OTA is excreted in urine, determination of urinary OTA requires sensitive analytical techniques, and phase-II-metabolites should be also considered as biomarkers of exposure. Yet, data published so far on the presence of OTA-glucuronide/sulfate in human urine have been contradictory. In this study, urines (n = 38) from two groups of breastfed infants (German and Turkish) and from German adults were now analysed for the presence of OTA glucuronides or sulfates by an indirect method, i.e. by comparing the levels of OTA (aglycone) in urines without and after enzymatic hydrolysis with ß-glucuronidase/arylsulfatase. Additionally, ochratoxin A-8-ß-glucuronide and open lactone ochratoxin A-8-ß-glucuronide were synthesized to serve as reference materials for metabolite analysis. Attempts for definitive confirmation of glucuronides of OTA via direct identification in LC-MS/MS analysis were hampered by the lower ionizability of the conjugates compared to the parent compound. Considerable increases in OTA levels were found after enzymatic hydrolysis in several (not all) urine samples and provide clear evidence for the excretion of OTA-conjugates. The latter observation is of importance, since OTA phase-II-metabolites may escape detection when direct methods are applied for urinary biomarker analysis. In conclusion, enzymatic hydrolysis of urine samples is highly advisable in order to avoid an underestimation of the OTA-exposure.

[Validation of a short test (3MS-R) for detecting Alzheimer's disease]. / Validierung eines kurzen Testverfahrens (3MS-R) für die Erkennung der Alzheimer-Demenz.

BACKGROUND: The Modified Mini-Mental State Examination-revised (3MS-R) is a brief cognitive test designed to detect cognitive impairment, which is often used in Canada and USA. OBJECTIVE: To assess the accuracy of the 3MS-R in identifying Alzheimer's disease (AD) in comparison with the conventional Mini-Mental State Examination (MMSE) in a German-speaking population. SUBJECTS: The study refers to 31 patients with early AD and 5 patients with moderate dementia of AD etiology, as well as to 46 age-matched cognitively normal participants. METHOD: The 3MS-R and the MMSE were validated against an expert diagnosis based on a comprehensive diagnostic workup. The 3MS scores were adjusted for educational attainment. Statistical analysis was performed using the Receiver Operating Characteristics (ROC). RESULTS: ROC curves demonstrated the superiority of the ACE over the MMSE in identifying AD (Area under the Curve: 3MS-R vs. MMSE: 0.995 vs.0.953). The optimal cut-off score for the 3MS for detecting AD was 88 and had a sensitivity of 98% and a specificity of 94%. The German version of the 3MS-R is a short and practical but accurate test battery for the identification of AD. The effectiveness of the German version of the test in detecting other forms of dementias or mild cognitive impairment could be a task for future studies.

Syringolin A, a new plant elicitor from the phytopathogenic bacterium Pseudomonas syringae pv. syringae, inhibits the proliferation of neuroblastoma and ovarian cancer cells and induces apoptosis.

Syringolin A is a new plant elicitor produced by the plant pathogen Pseudomonas syringae pv. syringae. The goal of this study was to investigate whether syringolin A exhibits anti-proliferative properties in cancer cells. The treatment of human neuroblastoma (NB) cells (SK-N-SH and LAN-1) and human ovarian cancer cells (SKOV3) with syringolin A (0-100 microm) inhibited cell proliferation in a dose-dependent manner. The IC(50) (50% inhibition) for each cell line ranged between 20 microm and 25 microm. In SK-N-SH cells, the treatment with 20 microm syringolin A led to a rapid (24 h) increase of the apoptosis-associated tumour suppressor protein p53. In addition, we found that the treatment of SK-N-SH cells caused severe morphological changes after 48 h such as rounding of cells and loss of adherence, both conditions observed during apoptosis. The induction of apoptosis by syringolin A was confirmed by both poly (ADP-ribose) polymerase (PARP) cleavage and annexin V assay. Taken together, we show for the first time that the natural product syringolin A exhibits anti-proliferative activity and induces apoptosis. Syringolin A and structurally modified syringolin A derivatives may serve as new lead compounds for the development of novel anticancer drugs.

[Validation of a Short Telephone Test (T3MS) for the Diagnosis of Cognitive Impairment]. / Validierung eines kurzen telefonischen Tests (T3MS) für die Erkennung kognitiver Störungen.

The identification of cognitive impairment in general practice requires short but accurate tests. For epidemiologic surveys and genetic family studies cognitive tests are desirable which can be administered over the telephone. We assessed the ability of a telephone version of the Modified Mini Mental State Examination (T3MS) to identify mild cognitive impairment (MCI) and mild dementia in Alzheimer's disease (AD) and compared it with the diagnostic accuracy of the conventional Mini Mental State Examination (MMSE). The study refers to 34 patients of the outpatient clinic for cognitive disorders of the technical university of Munich of whom 18 had MCI and 16 had mild dementia in AD, respectively. The study also included 14 cognitively unimpaired age-matched probands. The T3MS and MMST were validated against an expert diagnosis base on a comprehensive diagnostic workup. Statistical analysis was performed using the receiver-operator-characteristics (ROC) method. The T3MS outperformed the MMST in the distinction between MCI patients and cognitively unimpaired individuals. In the separation between cognitively unimpaired probands and patients with mild AD the T3MS achieved a sensitivity and specificity of 100 %. The T3MS is a short and practical but accurate telephone test for the identification of mild dementia in AD for use in epidemiological surveys and genetic family studies. The interview achieves higher diagnostic precision than the MMSE and contributes to a valid assessment of cognitive performance. For the identification of mild cognitive impairment, however, the T3MS was less appropriate.

Transient neurological symptoms with subarachnoid lidocaine: effect of early mobilization.

BACKGROUND AND OBJECTIVE: Although lidocaine has been used extensively for spinal anaesthesia since 1949, it has been associated with transient neurological symptoms only in the past 10 yr. It has been suggested that early ambulation after spinal anaesthesia, as opposed to traditional 24 h recumbency, might be the causative factor for the development of transient neurological symptoms. The purpose of this study was to examine the effect of early ambulation on the incidence of transient neurological symptoms after single injection spinal anaesthesia with lidocaine 2%. METHODS: Sixty patients undergoing minor surgery under spinal anaesthesia were included. All patients received lidocaine 60 mg. After the establishment of successful subarachnoid block, patients were randomly allocated to two groups of 30 patients. Patients in Group 1 were ambulated as soon as possible, whereas patients in Group 2 were kept recumbent until 6 h after subarachnoid injection. Two days after surgery patients were contacted by a blinded observer and interviewed of transient neurological symptoms using a standardized questionnaire. Patients were asked to express the intensity of pain/discomfort on a verbal rating scale from 0 (no pain) to 10 (worst pain imaginable). RESULTS: There was no significant difference in the incidence of transient neurological symptoms (23% vs. 27%). In all patients, symptoms resolved completely within 6-24 h. The median pain score was 5 (range 2-8) in Group 1 and 7 (range 1-8) in Group 2. CONCLUSIONS: Under the conditions of this study, there is no correlation between the time of ambulation after spinal anaesthesia with lidocaine and the incidence of transient neurological symptoms.

[Comparison of time-oriented cost accounting catalogs to control a department of radiology]. / Vergleich zeitorientierter Leistungskataloge zum Controlling einer radiologischen Abteilung.

PURPOSE: Within a hospital, the radiology department has taken over the role of a cost center. Cost accounting can be applied to analyze the costs for the performance of services. By assigning the expenditures of resources to the service, the cash value can directly be distributed to the costs of equipment, material and rooms. Time-oriented catalogs of services are predefined to calculate the number of the employees for a radiology department. Using our own survey of time data, we examined whether such catalogs correctly represent the time consumed in a radiology department. Only services relevant for the turnover were compared. MATERIALS AND METHODS: For 96 primary radiological services defined by the score-oriented German fee catalog for physicians (Gebuhrenordnung fur Arzte), a ranking list was made for the annual procedures in descending frequency order. According to the Pareto principle, the 11 services with the highest frequency were chosen and the time consumed for the technical and medical services was collected over a period of 2 months. This survey was compared with the time-oriented catalogs TARMED and EBM 2000plus. RESULTS: The included 11 relevant radiological services represented 80.3 % of the annual procedures of our radiology department. When comparing the technical services between the time-oriented catalogs and our own survey, TARMED gives a better description of the time consumed in 7 of the 11 services and EMB 2000plus in 3 services. When comparing the medical services, TARMED gives a better description of the time consumed in 6 of the 11 services and EBM 2000plus in 4 services. When averaging all the radiological services, TARMED overestimates the current number of physicians necessary for primary reading by a factor of 10.0 % and EBM 2000plus by a factor of 2.6 %. CONCLUSION: As to the time spent on performing the relevant radiological services, TARMED is slightly superior to describe the radiology department of a hospital than EBM 2000plus. For calculating the number of physicians necessary for primary reading, EBM 2000plus is superior to TARMED.

[Computer simulation of a clinical magnet resonance tomography scanner for training purposes]. / Computersimulation eines klinischen Magnetresonanztomographen für Ausbildungszwecke.

PURPOSE: The idea for this project was born by the necessity to offer medical students an easy approach to the theoretical basics of magnetic resonance imaging. The aim was to simulate the features and functions of such a scanner on a commercially available computer by means of a computer program. MATERIALS AND METHODS: The simulation was programmed in pure Java under the GNU General Public License and is freely available for a commercially available computer with Windows, Macintosh or Linux operating system. The graphic user interface is oriented to a real scanner. In an external program parameter, images for the proton density and the relaxation times T1 and T2 are calculated on the basis of clinical examinations. From this, the image calculation is carried out in the simulation program pixel by pixel on the basis of a pulse sequence chosen and modified by the user. The images can be stored and printed. In addition, it is possible to display and modify k-space images. RESULTS: Seven classes of pulse sequences are implemented and up to 14 relevant sequence parameters, such as repetition time and echo time, can be altered. Aliasing and motion artifacts can be simulated. As the image calculation only takes a few seconds, interactive working is possible. CONCLUSION: The simulation has been used in the university education for more than 1 year, successfully illustrating the dependence of the MR images on the measuring parameters. This should facititate the approach of students to the understanding MR imaging in the future.

[Development of a secure and cost-effective infrastructure for the access of arbitrary web-based image distribution systems]. / Entwicklung einer sicheren und kostengünstigen Infrastruktur zum Zugriff auf beliebige webbasierte Bildverteilungssysteme.

PURPOSE: To build an infrastructure that enables radiologists on-call and external users a teleradiological access to the HTML-based image distribution system inside the hospital via internet. In addition, no investment costs should arise on the user side and the image data should be sent renamed using cryptographic techniques. MATERIALS AND METHODS: A pure HTML-based system manages the image distribution inside the hospital, with an open source project extending this system through a secure gateway outside the firewall of the hospital. The gateway handles the communication between the external users and the HTML server within the network of the hospital. A second firewall is installed between the gateway and the external users and builds up a virtual private network (VPN). A connection between the gateway and the external user is only acknowledged if the computers involved authenticate each other via certificates and the external users authenticate via a multi-stage password system. All data are transferred encrypted. External users get only access to images that have been renamed to a pseudonym by means of automated processing before. RESULTS: With an ADSL internet access, external users achieve an image load frequency of 0.4 CT images per second. More than 90 % of the delay during image transfer results from security checks within the firewalls. Data passing the gateway induce no measurable delay. CONCLUSION: Project goals were realized by means of an infrastructure that works vendor independently with any HTML-based image distribution systems. The requirements of data security were realized using state-of-the-art web techniques. Adequate access and transfer speed lead to a widespread acceptance of the system on the part of external users.

v-Src phosphorylation of connexin 43 on Tyr247 and Tyr265 disrupts gap junctional communication.

The mechanism by which v-Src disrupts connexin (Cx)43 intercellular gap junctional communication (GJC) is not clear. In this study, we determined that Tyr247 (Y247) and the previously identified Tyr265 (Y265) site of Cx43 were the primary phosphorylation targets for activated Src in vitro. We established an in vivo experimental system by stably expressing v-Src and wild-type (wt) Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout mouse cell line. Wt and mutant Cx43 localized to the plasma membrane in the absence or presence of v-Src. When coexpressed with v-Src, the Y247F, Y265F, and Y247F/Y265F Cx43 mutants exhibited significantly reduced levels of tyrosine phosphorylation compared with wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in vivo. Most importantly, GJC established by the Y247F, Y265F, and Y247F/Y265F Cx43 mutants was resistant to disruption by v-Src. Furthermore, we did not find evidence for a role for mitogen-activated protein kinase in mediating the disruption of GJC by v-Src. We conclude that phosphorylation on Y247 and Y265 of Cx43 is responsible for disrupting GJC in these mammalian cells expressing v-Src.

[Biogeochemical processes of methane cycle in the soils, swamps and lakes of Western Siberia]. / Biogeokhimicheskie protsessy tsykla metana v pochvakh, bolotakh i ozerakh Zapadnoi Sibiri.

The biogeochemical processes of methane production and oxidation were studied in the upper horizons of tundra and taiga soils and of raised bogs and lake bottom sediments nearby the Tarkosalinsk gas field in western Siberia. Both in dry and water-logged soils, the total methane concentration (in soil particles and gaseous phase) was an order of magnitude higher than in the soil gaseous phase alone (22 and 1.1 nl/cm3, respectively). In bogs and lake bottom sediments, methane concentration was as high as 11 microliters/cm3. Acetate was the major precursor of the newly formed methane. The rate of aceticlastic methanogenesis reached 55 ng C/(cm3 day), whereas that of autotrophic methanogenesis was an order of magnitude lower. The most active methane production and oxidation were observed in bogs and lake sediments where the delta 13C values of CO2 were inversely related to the intensity of bacterial methane oxidation. Methane diffusing from bogs and lake bottom sediments showed delta 13C values ranging from -78 to -47@1000, whereas the delta 13C value of carbon dioxide ranged from -18 to -6@1000. In these ecosystems, methane emission comprised from 3 to 206 mg CH4/(m2 day). Conversely, the dry and water-logged soils of tundra and taiga took up atmospheric methane at a rate varying from 0.3 to 5.3 mg CH4/(m2 day). Methane consumption in soils was of biological rather than of adsorptive nature. This was confirmed by the radioisotopic method and chamber experiments, in which weighting of methane carbon was observed (the delta 13C value changed from -51 to -41@1000).

Contrast-enhanced magnetic resonance angiography of mammary artery grafts after minimally invasive coronary bypass surgery.

BACKGROUND: The aim of the study was to investigate the application of the contrast-enhanced magnetic resonance angiography (CE-MRA) for the visualization of left internal mammary artery (LIMA) bypass. METHODS: A total of 30 patients with LIMA bypass (22 men, 8 women, 35 to 77 years) received a CE-MRA 4 to 20 days after surgery. The non-ECG-triggered CE-MRA was performed during expiration using a body array coil at a 1.5 Tesla scanner (Magnetom-Vision). A three-dimensional gradient-echo sequence with slice interpolation technique was applied. For the three-dimensional visualization, single coronal slices were postprocessed with maximal intensity projection. Of 30 patients 22 agreed to a comparative coronary angiography. RESULTS: Five bypasses were identified up to the end-to-side anastomosis. A total of 80% of the bypass course was detectable in 13 patients and 60% in 11 patients. In two LIMA bypasses only 30% of the proximal part could be viewed; one was found by conventional coronary angiography to be occluded. The other conventional coronary angiography showed the LIMA bypass to be patent. CONCLUSIONS: The complete course of the LIMA bypass to the left anterior descending coronary artery can be visualized by the MRA technique. The most reliable imaging of the distal anastomosis can be realized by reducing the negative influence of the beating heart.

Cisterna magna clot and subsequent post-hemorrhagic hydrocephalus.

BACKGROUND: Posthemorrhagic hydrocephalus (PHH) is an ominous complication of intraventricular hemorrhage (IVH) in premature infants. Previous studies have correlated lateral intraventricular clot with subsequent PHH, but there are no studies assessing the outcome of clot in the cisterna magna (CM). OBJECTIVE: The purpose of this study was to determine if the identification of clot in the CM on the initial positive cranial ultrasound for intraventricular hemorrhage increased the risk of subsequent PHH. MATERIALS AND METHODS: A review of ultrasound records over a 4-year period identified 41 neonates with at least grade 2 IVH who had specific CM views prospectively performed. RESULTS: Thirty-six survived more than 3 months. Overall, 22 (61%) developed hydrocephalus. On the initial positive cranial ultrasound, CM blood was identified in 21 (58%). Of these 18 (86%) developed hydrocephalus [odds ratio (OR) 16.5, confidence interval (CI) 2.5-125.7, P < 0.001] and 14 (67%) required intervention or remained dilated (OR 28.0, CI 2.8-1265.8). All patients that required permanent shunt placement had initial CM clot (P < 0.01). Initial ventriculomegaly was not a significant predictor of subsequent hydrocephalus, but a dilated third ventricle (> or = 8 mm) was (OR 9.0, CI 1.2-103.3, P < 0.04). Asymmetric intraventricular clot filling of more than 50% was not predictive of hydrocephalus, but symmetric clot of more than 50% was (OR 10.8, CI 1.4-61.6, P < 0.01). Nine neonates had concomitant parenchymal damage with varying outcomes (three shunted, two persistent ventriculomegaly, four resolved with normal sized ventricles). CONCLUSION: In this study CM clot significantly increased the risk and was a better predictor of posthemorrhagic hydrocephalus than initial hydrocephalus.

v-Src-mediated phosphorylation of connexin43 on tyrosine disrupts gap junctional communication in mammalian cells.

It is not clear how the v-Src oncoprotein disrupts gap junctional communication (GJC) established by connexin43 (Cx43) in mammalian cells. In this study, an experimental system was established to stably express v-Src and wild type (wt) Cx43, or Y247F, Y265F, or Y247F/Y265F Cx43 mutants in a Cx43 knockout (KO) mouse cell line. When co-expressed with v-Src, the levels of phosphotyrosine (pTyr) from Y247F, Y265F, and Y247F/Y265F Cx43 mutants were reduced to approximately 57%, 10%, and 2% of the level of pTyr from wt Cx43, indicating that Y247 and Y265 were phosphorylation targets of v-Src in vivo. These data also implied that phosphorylation of Cx43 at Y265 was required for efficient phosphorylation of Cx43 at Y247. Most importantly, our measurements of GJC demonstrated that, in contrast to the wt Cx43 gap junction channels, the Y247F, Y265F, and Y247F/Y265F Cx43 channels were resistant to the disruption by v-Src. In conclusion, our studies support a model for processive phosphorylation of Cx43 on tyrosine, at the Y265 site followed by the Y247 site, in mediating the disruption of GJC induced by v-Src in mammalian cells.

[Depression in the child]. / Les dépressions chez l'enfant.

Since Spitz's description of anaclitic depression in 1945, it has been widely recognized that children, even very young, suffer from depression. Recent research suggests that depression persists during the developmental stages and depressed children are more likely to become depressed adults than their peers. This underlines the importance of diagnosing and treating depression at a young age. Pediatricians should be fully aware of the signs and symptoms of depression as they are first in line to identify and prevent it. This article covers clinical description of depression in infants and young children, as well as its etiology and treatment.

Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and language phenotypes.

This is the first clinical description of a detailed psychological, speech, and language phenotype of four young children (< 5 years) with Velo-Cardio-Facial syndrome (VCFS) due to a deletion on chromosome 22 (22q11.2). The reported elevated risk of developing schizophrenia or bipolar disorder in adolescence for individuals with this chromosomal deletion led us to examine the psychiatric and cognitive status of young children with VCFS. Our observations suggest a phenotype comprised of a borderline to mildly retarded level of intellectual functioning, a language delay, a general deficit in social initiation, difficulties with attention/concentration, and a perturbed train of thought.

Kyphomelic dysplasia: a rare form of semilethal skeletal dysplasia.

Kyphomelic dysplasia is a rare form of generalized skeletal dysplasia with about 15 cases described so far in the literature. We present the clinical, radiological, and pathological findings of an antenatally detected female fetus affected with this disorder. The differential diagnoses of prenatal and perinatal semilethal skeletal dysplasias and salient features of documented cases of kyphomelic dysplasia are presented.