Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI.

PURPOSE: PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). METHODS: Eight patients with gliomas were investigated simultaneously with 18F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B1 average power of 1µT. B0 field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTRasym) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test. RESULTS: A tumour-to-brain ratio derived from APT# and 18F-FET presented no significant differences, and no correlation was found between APT# and 18F-FET PET data. The distance between local hot spot APT# and 18F-FET were different (average 20 ± 13 mm, range 4-45 mm). CONCLUSION: For the first time, CEST images were compared with 18F-FET in a simultaneous MR-PET measurement. Imaging findings derived from18F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

Nuclear size and nuclear binding of tritiated actinomycin D into epithelial cells of colon cancer patients with apparently normal colorectal mucosa.

The nuclear binding of tritiated actinomycin ([3H]AM) is clearly linked to the structural organization of the chromatin. [3H]AM decreases in cells which differentiate and becomes very low in fully differentiated cells. [3H]AM nuclear binding and nuclear size were concomitantly measured in normal-appearing flat mucosa of 10 patients bearing a colorectal cancer and compared with the colon mucosa of 10 normal individuals. In the colon of these normal subjects, there is a decreasing gradient of labeling in the upper third of the gland, with heavy labeling in the lower two-thirds and light labeling in surface epithelial cells. The ratio (R) of grain count in cells in the bottom of the glands to grain count in the surface epithelial cell varies in normal subjects from 4 to 14. There is no correlation between nuclear size and [3H]AM binding. In normal-appearing flat mucosa of cancerous patients, there is no decrease of labeling [3H]AM in the upper third of the glands; superficial cells are as labeled as those at the bottom (R = 1). There is a correlation between nuclear size and [3H]AM in these cells. Normal-appearing cells of colorectal cancer patients are probably not involved in a normal process of differentiation.

Multimodal Imaging in Malignant Brain Tumors: Enhancing the Preoperative Risk Evaluation for Motor Deficits with a Combined Hybrid MRI-PET and Navigated Transcranial Magnetic Stimulation Approach.

BACKGROUND AND PURPOSE: Motor deficits in patients with brain tumors are caused mainly by irreversible infiltration of the motor network or by indirect mass effects; these deficits are potentially reversible on tumor removal. Here we used a novel multimodal imaging approach consisting of structural, functional, and metabolic neuroimaging to better distinguish these underlying causes in a preoperative setting and determine the predictive value of this approach. MATERIALS AND METHODS: Thirty patients with malignant brain tumors involving the central region underwent a hybrid O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET-MR imaging and motor mapping by neuronavigated transcranial magnetic stimulation. The functional maps served as localizers for DTI tractography of the corticospinal tract. The spatial relationship between functional tissue (motor cortex and corticospinal tract) and lesion volumes as depicted by structural and metabolic imaging was analyzed. RESULTS: Motor impairment was found in nearly all patients in whom the contrast-enhanced T1WI or PET lesion overlapped functional tissue. All patients who functionally deteriorated after the operation showed such overlap on presurgical maps, while the absence of overlap predicted a favorable motor outcome. PET was superior to contrast-enhanced T1WI for revealing a motor deficit before the operation. However, the best correlation with clinical impairment was found for T2WI lesion overlap with functional tissue maps, but the prognostic value for motor recovery was not significant. CONCLUSIONS: Overlapping contrast-enhanced T1WI or PET-positive signals with motor functional tissue were highly indicative of motor impairment and predictive for surgery-associated functional outcome. Such a multimodal diagnostic approach may contribute to the risk evaluation of operation-associated motor deficits in patients with brain tumors.

Carnocin UI49, a potential biopreservative produced by Carnobacterium piscicola: large scale purification and activity against various gram-positive bacteria including Listeria sp.

This paper describes a simple purification method for the purification of carnocin UI49, a potential biopreservative produced by Carnobacterium piscicola UI49. The protocol was also applicable for the isolation of nisin Z, which is a biopreservative produced by Lactococcus lactis SIK-83. The protocol consists of only two purification steps, XAD chromatography and cation exchange chromatography. It is quick, easy, and can be used for large scale purification of these lantibiotics. The bactericidal activity of carnocin UI49 against carnobacteria, lactococci and Listeria was compared with that of nisin Z. The carnobacteria showed similar sensitivity towards carnocin UI49 and nisin. The nisin producing L. lactis strains were very sensitive towards carnocin UI49, while the non-producing L. lactis strains were more sensitive to nisin. The Listeria strains were weakly sensitive to carnocin UI49, lower concentrations of nisin were needed to inhibit growth.

[Sexually-transmissible anorectal diseases]. / Maladies anorectales sexuellement transmissibles.

Several anorectal diseases are described. Most are sexually transmitted (gay bowel syndrome or heterosexual transmission). The clinical aspect of nearly all of them is similar. Thus, the diagnosis usually cannot be done on clinical grounds alone: one has to request the help of the laboratory. Amebiasis, giardiasis, chancroid and donovanosis are frequent in Africa but rare in our countries, except in male homosexuals. Shigellosis, salmonellosis, pediculosis, scabies and campylobacter infections are seen in male homosexuals because of orofecal contacts. Condylomata acuminata are frequent in our country. The typical clinical aspect leads to an easy diagnosis. Electrocoagulation is the treatment of choice. Anorectal gonococcal are also frequent in our country, both homosexually and heterosexually transmitted. The clinical aspect suggests the diagnosis, but this must be confirmed by the laboratory.

[Natural history and classification of HIV-virus infections]. / Histoire naturelle et classification de l'infection par le virus H.I.V.

Clinical concepts about the acquired immunodeficiency syndrome, are evolving constantly. Laboratory tests are used to prove the infection virologically and serologically, to quantify the importance of immunodeficiency and to give a tentative prognosis. We discuss three classification systems (CDC, Haverkos, Walter Reed). They are more or less precise and suitable. They may indicate the status of the disease, from seroconversion up to opportunistic infections and secondary cancers. Then we compare those different systems of classification, their advantages and disadvantages. These classification systems may change with evolving concepts about the syndrome.

[Acute mastoiditis: 16 clinical cases]. / Akute mastoïditis: 16 klinische gevallen.

Sixteen cases of acute mastoiditis were treated between 1980 and 1984. In infants the course of the mastoiditis was brief. An external retroauricular swelling soon occurred that was generally due to edema without abscess formation, and medical treatment resulted in rapid healing. For the older children, the acute mastoiditis occurred on an acute otitis media that had already been present for some time. Abscess formation occurred in half of the cases, and a mastoidectomy was generally required. For the adult patients, there was always an underlying chronic ear pathology, either a cholesteatoma or a chronic benign middle ear infection. Surgical intervention was always required both for the treatment of the underlying pathology and for the acute associated infection.

Membrane-associated proteins encoded by the nisin gene cluster may function as a receptor for the lantibiotic carnocin UI49.

Carnocin UI49, a lantibiotic produced by Carnobacterium piscicola shows bactericidal activity against many lactic acid bacteria. This paper describes the results of a study on the mode of action of carnocin UI49. It has previously been observed that nisin-producing Lactococcus lactis subsp. lactis strains are at least 10-fold more sensitive to carnocin UI49 relative to other lactic acid bacteria. Addition of carnocin UI49 to cells of L. lactis subsp. lactis NZ9700 resulted in a dissipation of the membrane potential and a rapid hydrolysis of internal ATP. These results suggest that carnocin UI49 may act at the cytoplasmic membrane. The correlation between production of and/or immunity to nisin and sensitivity to carnocin of L. lactis subsp. lactis strains was further investigated. Several transformed L. lactis subsp. lactis strains carrying a fragment of the nisin gene cluster were tested for their sensitivity to carnocin UI49 and their immunity to nisin. The results suggest that NisP, which is one of the membrane-associated proteins involved in the production of nisin acts as receptor for carnocin UI49. This may facilitate the binding and/or insertion of carnocin UI49 into the cytoplasmic membrane thus increasing its bactericidal activity. Lantibiotic-producing and non-producing mutants of Staphylococcus epidermidis and Lactobacillus sake did not show a difference in sensitivity to carnocin UI49. The proposed receptor-mediated action of carnocin UI49 at the cytoplasmic membrane therefore seems to be specific for the nisin-producing strains.

[On the enteral absorption of valproic acid (author's transl)]. / Zur enteralen Resorption von Valproinsäure

The absorption of valproic acid (dipropylacetic acid, DPA)--administered by capsules (free valproic acid) and dragees (valproate sodium)--has been studied. Regarding their bioavailability, both forms of administration examined are equivalent, which means that they are representing therapeutical alternatives.

Cell differentiation in human gastric gland as revealed by nuclear binding of tritiated actinomycin.

The nuclear binding of H3 actinomycin, which is closely linked to the differentiation phenomenon, was studied in human normal gastric mucosa. Actinomycin binding decreases in cells which differentiate and becomes very low in fully differentiated cells. In the gastric pits, there is a decreasing gradient of labelling from the deeper stem cells to the well-differentiated superficial cells. This indicates that migration and renewal of the surface epithelium occurs following a 'pipe-line' system. All the undifferentiated stem cells are labelled. Where the parietal cells are concerned all degrees of labelling are observed at various levels with a decreasing proportion of labelling from the surface to the bottom of the gland. With mucous cells and chief cells in the upper part of the gland a great number of poorly labelled mucous neck cells is observed. In the middle and lower part of the gland there is a new growth of heavily labelled cells. This means that in the normal human stomach chief cells probably do not originate from mucous cells.

Isolation and properties of a bacteriocin-producing Carnobacterium piscicola isolated from fish.

A facultative psychrotrophic lactic acid bacterium isolated from fresh fish was identified as Carnobacterium piscicola on the basis of carbohydrate utilization, G + C content and 16S RNA analysis. Its bacteriocin, designated carnocin UI49, is produced during the mid-exponential phase of growth at temperatures between 15 degrees C and 34 degrees C. Carnocin UI49 is active against a large number of closely-related lactic acid bacteria including carnobacteria, lactobacilli, pediococci and lactococci. Furthermore, the bacteriocin has a bactericidic mode of action which results in lysis of sensitive cells. Maximum bactericidal activity is observed at 34 degrees C with a decrease in activity down to 15 degrees C where it is completely abolished.

[Evaluation of cases with positive Toxoplasma IgM antibodies within the scope of prenatal care]. / Abklärung von Fällen mit positivem Toxoplasma-IgM-Antikörpernachweis im Rahmen der Schwangerenvorsorge.

Follow up sera from pregnant women were taken and examined according to the suggestions of the German Advisory Board "Toxoplasmosis and Pregnancy". The results gained support the guidelines of the board and additional advice for the clarification of cases are given.

Nuclear binding of tritiated actinomycin in surface epithelial cells from normal stomach and atrophic gastritis.

Triated actinomycin binding to DNA is closely linked to the degree of repression in chromatin. 3H-AM binding to DNA is the most pronounced in nuclei of cells committed into cycle. Inversely, in cells in the last steps of their differentiation or (and) in the resting state (non-dividing cells), 3H-AM binding for DNA is diminished down to a baseline since it is limited by the deoxynucleoproteins. Epithelial cells of stomach mucosa and duodenum demonstrate an increased cell uptake of tritiated actinomycin from the surface to the bottom of the pits. In severe gastritis and in intestinalysed metaplasia this was abolished: with a uniform enhancement of 3H-AM binding. These findings seem to indicate that these cells are derepressed.

[Biological disorders of alcoholic origin]. / Troubles biologiques d'origine alcoolique

Chronic alcoholism tends to alter the serum levels of numerous blood components. In comparing the serum levels of these elements in a noncirrhotic chronic alcoholic patient after withdrawal, the authors determined a characteristic biological table. The serum factors demonstrating a significant difference after the withdrawal of alcohol were as follows: total cholesterol, triglycerides, total lipids, total bilirubin, SGOT, SGPT, alkaline phosphatase, serum iron, uric acid, hematocrit and the number of red blood cells. It is noteworthy that these tests are those of routine and can be performed in any modestly equipped laboratory.