A combination of atlas-based and voxel-wise approaches to analyze metabolic changes in autoradiographic data from Alzheimer's mice.

Murine models are commonly used in neuroscience research to improve our knowledge of disease processes and to test drug effects. To accurately study brain glucose metabolism in these animals, ex vivo autoradiography remains the gold standard. The analysis of 3D-reconstructed autoradiographic volumes using a voxel-wise approach allows clusters of voxels representing metabolic differences between groups to be revealed. However, the spatial localization of these clusters requires careful visual identification by a neuroanatomist, a time-consuming task that is often subject to misinterpretation. Moreover, the large number of voxels to be computed in autoradiographic rodent images leads to many false positives. Here, we proposed an original automated indexation of the results of a voxel-wise approach using an MRI-based 3D digital atlas, followed by the restriction of the statistical analysis using atlas-based segmentation, thus taking advantage of the specific and complementary strengths of these two approaches. In a preliminary study of transgenic Alzheimer's mice (APP/PS1), and control littermates (PS1), we were able to achieve prompt and direct anatomical indexation of metabolic changes detected between the two groups, revealing both hypo- and hypermetabolism in the brain of APP/PS1 mice. Furthermore, statistical results were refined using atlas-based segmentation: most interesting results were obtained for the hippocampus. We thus confirmed and extended our previous results by identifying the brain structures affected in this pathological model and demonstrating modified glucose uptake in structures like the olfactory bulb. Our combined approach thus paves the way for a complete and accurate examination of functional data from cerebral structures involved in models of neurodegenerative diseases.

Reduced and stable feature sets selection with random forest for neurons segmentation in histological images of macaque brain.

In preclinical research, histology images are produced using powerful optical microscopes to digitize entire sections at cell scale. Quantification of stained tissue relies on machine learning driven segmentation. However, such methods require multiple additional information, or features, which are increasing the quantity of data to process. As a result, the quantity of features to deal with represents a drawback to process large series or massive histological images rapidly in a robust manner. Existing feature selection methods can reduce the amount of required information but the selected subsets lack reproducibility. We propose a novel methodology operating on high performance computing (HPC) infrastructures and aiming at finding small and stable sets of features for fast and robust segmentation of high-resolution histological images. This selection has two steps: (1) selection at features families scale (an intermediate pool of features, between spaces and individual features) and (2) feature selection performed on pre-selected features families. We show that the selected sets of features are stables for two different neuron staining. In order to test different configurations, one of these dataset is a mono-subject dataset and the other is a multi-subjects dataset to test different configurations. Furthermore, the feature selection results in a significant reduction of computation time and memory cost. This methodology will allow exhaustive histological studies at a high-resolution scale on HPC infrastructures for both preclinical and clinical research.

Validation of MRI-based 3D digital atlas registration with histological and autoradiographic volumes: an anatomofunctional transgenic mouse brain imaging study.

Murine models are commonly used in neuroscience to improve our knowledge of disease processes and to test drug effects. To accurately study neuroanatomy and brain function in small animals, histological staining and ex vivo autoradiography remain the gold standards to date. These analyses are classically performed by manually tracing regions of interest, which is time-consuming. For this reason, only a few 2D tissue sections are usually processed, resulting in a loss of information. We therefore proposed to match a 3D digital atlas with previously 3D-reconstructed post mortem data to automatically evaluate morphology and function in mouse brain structures. We used a freely available MRI-based 3D digital atlas derived from C57Bl/6J mouse brain scans (9.4T). The histological and autoradiographic volumes used were obtained from a preliminary study in APP(SL)/PS1(M146L) transgenic mice, models of Alzheimer's disease, and their control littermates (PS1(M146L)). We first deformed the original 3D MR images to match our experimental volumes. We then applied deformation parameters to warp the 3D digital atlas to match the data to be studied. The reliability of our method was qualitatively and quantitatively assessed by comparing atlas-based and manual segmentations in 3D. Our approach yields faster and more robust results than standard methods in the investigation of post mortem mouse data sets at the level of brain structures. It also constitutes an original method for the validation of an MRI-based atlas using histology and autoradiography as anatomical and functional references, respectively.

Hair dosimetry following neutron irradiation.

Use of hair as a biological dosimeter of neutron exposure was proposed a few years ago. To date, the (32)S(n,p)(32)P reaction in hair with a threshold of 2.5 MeV is the best choice to determine the fast neutron dose using body activation. This information is essential with regards to the heterogeneity of the neutron transfer to the organism. This is a very important parameter for individual dose reconstruction from the surface to the deeper tissues. This evaluation is essential to the adapted management of irradiated victims by specialized medical staff. Comparison exercises between clinical biochemistry laboratories from French sites (the CEA and COGEMA) and from the IRSN were carried out to validate the measurement of (32)P activity in hair and to improve the techniques used to perform this examination. Hair was placed on a phantom and was irradiated at different doses in the SILENE reactor (Valduc, France). Different parameters were tested: variation of hair type, minimum weight of hair sample, hair wash before measurement, delivery period of results, and different irradiation configurations. The results obtained in these comparison exercises by the different laboratories showed an excellent correlation. This allowed the assessment of a dose-activity relationship and confirmed the feasibility and the interest of (32)P measurement in hair following fast neutron irradiation.

Development of a database: DACTARI for a radiotoxic element ranking methodology.

Dosimetric impact studies aim at evaluating potential radiological effects of chronic or acute releases from nuclear facilities. A methodology for ranking radionuclides (RN) in terms of their health-related impact on the human population was first developed at CEA with specific criteria for each RN that could be applied to a variety of situations. It is based, in particular, on applying physico-chemical criteria to the complete RN inventory (present in the release or in the source term) and on applying norms related to radiation protection and chemical toxicology. The initial step consisted in identifying and collecting data necessary to apply the methodology, with reference to a previous database of long-lived radionuclides (LLRN, with half-lives ranging from 30 to 10(14) y) containing 95 radionuclides. The initial results have allowed us to identify missing data and revealed the need to complete the study for both toxic and radiotoxic aspects. This led us to the next step, developing a specific database, DAtabase for Chemical Toxicity and Radiotoxicity Assessment of RadIonuclides (DACTARI), to collect data on chemical toxicity and radiotoxicity, including acute or chronic toxicity, the chemical form of the compounds, the contamination route (ingestion, inhalation), lethal doses, target organs, intestinal and maternal-foetal transfer, drinking water guidelines and the mutagenic and carcinogenic properties.

Recurrent chromosome aberrations in human lung squamous cell carcinomas.

Cytogenetic study of seven cases of previously untreated lung squamous cell carcinomas (SQC) is reported. Chromosome numbers vary from 38 to 538, with a majority of hypotriploid karyotypes with complex rearrangements. The numbers of recurrent imbalances were evaluated in considering the average number of chromosomes or chromosome segments in each analyzed metaphase and for each case. In decreasing order of frequency, deficiencies for 3p, 5q, 8p, Y, 5p, 10p, 13, and, to a lesser degree, for 8q, 9, 10q, 11pter, 14, 15, and 21 were observed; the excesses principally involve 1q, 3q, and 7q. In three tumors, homogeneously staining regions were observed at various chromosome sites. Most chromosome rearrangements occurred after breakage in constitutive heterochromatin, and no recurrent breakpoints were found in euchromatin except 11p15. The major consequences of these anomalies may be chromosomal imbalances, leading to hemizygosity and perhaps related to gene dosage, rather than to alterations of genes.

Cytogenetic study of five cases of lung adenosquamous carcinomas.

The cytogenetic study of five cases of untreated adenosquamous carcinoma of the lung allows us to propose a number of characteristic anomalies. All tumor cells were hyperdiploid, with a mean chromosome number ranging from 59 to 83, and had many clonal chromosome rearrangements. The chromosomes the most frequently affected by these rearrangements were, by decreasing order, 1, 3, and 15; 7 and 8; and 17. No recurrent breakpoints were observed in euchromatic regions, most breaks (45/66) involving juxtacentromeric heterochromatin or immediately adjacent regions. Although chromosome 3 was frequently rearranged, no recurrent deletions of its short arm were observed.

Radiation-induced chromosome damage in astronauts' lymphocytes.

The increased number of manned space missions has made it important to estimate the biological risks encountered by astronauts. As they are exposed to cosmic rays, especially ions with high linear energy transfer (LET), it is necessary to estimate the doses they receive. The most sensitive biological dosimetry used is based on the quantification of radiation-induced chromosome damage to human lymphocytes. After the space missions ANTARES (1992) and ALTAIR (1993), we performed cytogenetic analysis of blood samples from seven astronauts who had spent from 2 weeks to 6 months in space. After 2 or 3 weeks, the X-ray equivalent dose was found to be below the cytogenetic detection level of 20 mGy. After 6 months, the biological dose greatly varied among the astronauts, from 95 to 455 mGy equivalent dose. These doses are in the same range as those estimated by physical dosimetry (90 mGy absorbed dose and 180 mSv equivalent dose). Some blood cells exhibited the same cytogenetic pattern as the 'rogue cells' occasionally observed in controls, but with a higher frequency. We suggest that rogue cells might result from irradiation with high-LET particles of cosmic origin. However, the responsibility of such cells for the long-term effects of cosmic irradiation remains unknown and must be investigated.

Chromosomal aberrations induced by low-dose gamma-irradiation. Study of R-banded chromosomes of human lymphocytes.

The effect of low-dose (0-0.5 Gy) gamma-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas that of deletions decreases.

Aneuploidy in human lymphocytes: an extensive study of eight individuals of various ages.

Data on aneuploidy from a prospective study on a large number of lymphocyte metaphases (over 1000 in 72-h and 100 in 48-h cultures) per individual from eight healthy donors of various ages are reported. Chromosome losses were dependent on culture time, being significantly more frequent in 72-h than in 48-h cultures. All donors exhibited various degrees of aneuploidy which increased with age in women. This increase resulted essentially from X chromosome losses, as previously reported. Although the rate of aneuploidy limited to autosomes was similar in newborns and in adults, the distributions of the missing autosomes were different. In the two newborns studied, autosome aneuploidy was random. In the adults, a significant inverse correlation with autosome lengths was observed. The inverse correlation between chromosome lengths and losses may be explained by selective pressure against monosomic cells in the adults.

Study of uranium transfer across the blood-brain barrier.

Uranium is a heavy metal which, following accidental exposure, may potentially be deposited in human tissues and target organs, the kidneys and bones. A few published studies have described the distribution of this element after chronic exposure and one of them has demonstrated an accumulation in the brain. In the present study, using inductively coupled plasma mass spectrometry (ICP-MS) for the quantification of uranium, uranium transfer across the blood-brain barrier (BBB) has been assessed using the in situ brain perfusion technique in the rat. For this purpose, a physiological buffered bicarbonate saline at pH 7.4 containing natural uranium at a given concentration was perfused. After checking the integrity of the BBB during the perfusion, the background measurement of uranium in control rats without uranium in the perfusate was determined. The quantity of uranium in the exposed rat hemisphere, which appeared to be significantly higher than that in the control rats, was measured. Finally, the possible transfer of the perfused uranium not only in the vascular space but also in the brain parenchyma is discussed.

[Hemospermia]. / Hémospermie.

Haemospermia is a relatively frequent symptom in urology, especially in young subjects. It is often benign, but is important because of the anxiety it can cause to the patient. The predominant aetiology of haemospermia is prostatic and seminal vesicle disease. Iatrogenic aetiologies, generally without severity, are due to the development of instrumental diagnosis and treatment in urology. Recent progress in the field of medical imaging, particularly transrectal ultrasonography and magnetic resonance imaging, has greatly contributed to the diagnostic and therapeutic approach to haemospermia.

[Infection on foreign material: bacterial colonization of ureteral endoprostheses]. / Infection sur matériel étranger: colonisation bactérienne des endoprothèses urétérales.

Infection on foreign body: bacterial colonization of ureteric stents. The most frequent cause of the early removal of ureteric endoprostheses (double J) is generally due to bacterial colonization. In order to prevent or to restrict the prosthesis colonization, it is necessary to understand the major steps and the factors influencing the colonization. This is the reason why we aimed to extract the most relevant parameters influencing the bacterial colonization from the observations made in vivo thanks to in vitro analyses. We have studied in vivo the relationship between the bacterial colonization of the endoprostheses, the urinary infections and the antibiotherapy. In vitro, we have defined the conditions promoting the primary adhesion of the most frequently isolated bacteria on endoprostheses. Surface properties of bacteria and materials have been compared to:--the bacterial count of infected double J samples with respect to bacterial species,--the bacterial count of the infected samples with respect to pH and Ca2+, Mg2+ concentration. The results show a great variability of the biomaterial surface properties which could be optimized, the fact that the urinary medium acidification could lower the bacterial adhesion and the ambiguous role of Ca2+ and Mg2+ ions which is discussed in this paper. In the case of in vivo analyses, the conflicting results between leukocyturia and bacteriuria lead to the detection of the bacterial colonization under antibiotic treatment. The characterized urinary infection must warn the risk of pyelonephritis.

[Role of biofilm in urology]. / Rôle du biofilm en urologie.

The particular organization of bacteria as a biofilm on surfaces plays an essential role in urology because of the increasing use of prosthetic materials. Although the biocompatibility of the various materials used is now more effectively controlled, colonization of surfaces by microorganisms is frequent and the formation of a biofilm is responsible for difficulties encountered during treatment of prosthetic infections. The problems concerning the detection and eradication of biofilm led the authors to propose a brief review of the growing understanding of biofilm in urology over the last five years.

[Treatment of female stress urinary incontinence with cystocele by Gore Tex colpofixation and Burch operation]. / Traitement de l'incontinence urinaire féminine d'effort avec cystocèle par promontofixation utérine au Gore Tex et intervention de Burch.

OBJECTIVE: We treat female urinary stress incontinence (USI) with cystocele with or without associated genital prolapse by a combination of sacral colpopexy and Burch anterior colposuspension. We evaluated the results of a consecutive series of 77 patients completing a telephone interview after a mean follow-up of 40.6 months (range: 15 to 74 months). MATERIAL AND METHODS: From January 1991 to December 1995, 77 patients (mean age: 56.7 years) underwent Gore-Tex sacral colpopexy and Burch colposuspension for USI. Levator ani myorrhaphy was also performed in 53 severe cases. Incontinence was severe in every case, and associated with stage > or = 2 cystocele in 93% of cases. Urodynamic assessment revealed detrusor instability (DI) in 17.3% of cases and sphincter insufficiency (SI) < or = 35 cm H2O in 11.9% of cases. The main complications were: 4 haemorrhages requiring transfusion of one unit, 2 wound abscesses, one wall haematoma, and one small bowel obstruction at the 4th month, treated surgically. RESULTS: Six patients were lost to follow-up (good early results) and 2 files could not be analysed with sufficient follow-up (patients died from other diseases). Good results were defined by at least two of the following criteria: patient satisfied, no incontinence and no need for protective pads. We obtained 59 successes (85.5%) and 10 failures (14.5%). The results remained stable over time with 88.8% of success after a follow-up of more than 60 months (20 patients). Nine of the 10 failures occurred during the first year. They were demonstrated by the survey, while the post-operative follow-up at one month had been satisfactory. No specific treatment was therefore proposed. The two main factors of failures were DI and severe SI. Three times more failures were observed when the preoperative closure pressure were less than 30 cm H2O. CONCLUSION: Sacral colpopexy combined with Burch operation is a reliable solution for repair of USI with marked cystocele. It ensures good initial results which persist at one year and in the long-term.

[Primary renal chondrosarcoma: apropos of a case]. / Le chondrosarcome rénal primitif: à propos d'un cas.

The authors report a case of primary renal chondrosarcoma associated with subcapsular renal haematoma. The authors reviewed the four largest series of renal sarcomas reported in the literature and propose an analysis of the various clinical characteristics, complementary investigations and treatment modalities of this exceptional form of renal sarcoma.

[Current role of coagulase-negative staphylococci in urology]. / Place actuelle des staphylocoques à coagulase négative en urologie.

Coagulase-negative Staphylococci (CNS), considered for many years to be commensal bacteria of the skin are now recognized as major agents of nosocomial infection. Bacterial factors (increased resistance), host factors (immune status) and multiplication of the portals of entry (presence of foreign material) have contributed to the increased incidence of nosocomial infections. The importance of the role of NCS in urology is due to their great capacity to colonize catheters and most prostheses. The particular organization of these bacteria into a conglomerate called biofilm is responsible for prosthetic infections, which can impair renal function and can sometimes be life-threatening. The authors review the current increase of the number of CNS isolated in urology departments and describe the various therapeutic strategies that can be proposed to eradicate these bacteria.

[Prostatic abscesses: what treatment to propose?]. / Abcès prostatiques: quelles thérapeutiques proposer?

Microscopic abscesses of the prostate (< 1 cm) are usually treated by antibiotics with good prostatic diffusion, such as fluoroquinolones, for a minimum of 4 to 6 weeks. Complementary surgical drainage is generally required for larger abscesses or in case of an unfavourable course. The main points of discussion in the literature are the type of drainage and the incision that should be performed. Prostatic abscesses used to be drained via perineal incisions, but with a high mortality. The use of effective antibiotics has significantly improved the morbidity of prostatic abscesses. CT-guided percutaneous drainage (perineal or transrectal), or more frequently transrectal ultrasound-guided drainage, now allows rapid and effective evacuation of the abscess, without the need for general anaesthesia. The perineal route allows a simple J stent to be left in place for several days to ensure complete drainage, but it is not universally accepted. Transurethral exposure is indicated for periurethral prostatic abscesses.

[Improvement over time of oncological results after radical prostatectomy: what are the responsible factors?]. / Amélioration au cours du temps des résultats carcinologiques après prostatectomie radicale: quels en sont les facteurs responsables?

OBJECTIVES: The histological results after radical prostatectomy constitute one of the main prognostic factors. We studied the course of these results over time in order to assess their improvement and to identify the factors responsible. MATERIAL AND METHODS: 175 radical prostatectomies were performed between 1989 and 1996. The preoperative assessment for each patient comprised clinical examination, PSA assay, and histological examination of 6 ultrasound-guided transrectal biopsies. All radical prostatectomy specimens were analysed according to the Stanford technique by the same pathologist: the weight of the prostatectomy specimen, the Gleason score, existence of capsular effraction, seminal vesicle invasion, positive lymph node dissection and the presence of positive surgical margins were studied. The results were studied and compared year by year using Student's test and the Chi-square test. RESULTS: From 1989 to 1996, stages pT1-pT2 increased from 40 to 81.8%, while the positive resection margin rate decreased from 80 to 18.1%. No difference was observed over time for weight and Gleason score. Among the preoperative factors, no difference was observed for age of the patients, number of positive biopsies and Gleason score of these biopsies. Only the mean preoperative PSA level decreased from 52.2 to 12.2 ng/ml (t = 0.0001) and the number of stage T1c tumours increased from 13.3 to 59%. CONCLUSION: The preoperative PSA level is the main factor explaining improvement of the oncological results, especially as the tumours operated between 1988 and 1996 were identical in terms of aggressiveness (Gleason score). This improvement of the results reflects better patient selection, although this selection is performed case by case without exclusive factors.

[Feasibility and toxicity of a single fraction high-dose-rate brachytherapy followed by a course of EBRT for localized prostate cancer: a retrospective study. The Polyclinique Courlancy experience]. / Faisabilité et toxicité d'une séance unique de curiethérapie de haut débit de dose suivie d'une irradiation externe dans le cancer localisé de la prostate : étude rétrospective de la polyclinique de Courlancy.

PURPOSE: Evaluate the feasibility and toxicity of radiation dose escalation delivered with a single fraction high-dose-rate (HDR) brachytherapy boost followed by external beam radiotherapy for intermediate and high risk localized prostate cancer - a retrospective study. PATIENTS AND METHODS: Between December 2004 and December 2008, 61 patients with intermediate risk or high-risk localized prostate cancer received a single 10 Gy fraction of interstitial HDR brachytherapy followed by a 64 Gy course of external beam radiation therapy. Dose volume histograms, conformity index and side effects were systematically analyzed. RESULTS: HDR brachytherapy dosimetric criteria were respected. Early side effects (< or = 3 months after full treatment): 30 % reported grade 2 or grade 3 urinary toxicity and 26 % reported grade 2 or grade 3 bowel toxicity were reported. Late side effects (> 3 months): 12 % reported grade 2 or grade 3 urinary toxicity and 5 % reported grade 2 or grade 3 bowel toxicity were reported. No patients reported any grade 4 late toxicity events. Three months after treatment, 7 % grade 1, 25 % grade 2 and 39 % grade 3 erectile dysfunction were reported. CONCLUSION: Our monofractionation protocol is an easy technique to implement logistically. Acute and late toxicities are acceptable and comparable to those published by various teams mostly using multifractionation protocols. A longer follow-up is required to assess the effect of this dose escalation protocol on long-term biological control.