Three-dimensional (3D) culture of adult murine colon as an in vitro model of cryptosporidiosis: Proof of concept.

Cryptosporidium parvum is a major cause of diarrheal illness and was recently potentially associated with digestive carcinogenesis. Despite its impact on human health, Cryptosporidium pathogenesis remains poorly known, mainly due to the lack of a long-term culture method for this parasite. Thus, the aim of the present study was to develop a three-dimensional (3D) culture model from adult murine colon allowing biological investigations of the host-parasite interactions in an in vivo-like environment and, in particular, the development of parasite-induced neoplasia. Colonic explants were cultured and preserved ex vivo for 35 days and co-culturing was performed with C. parvum. Strikingly, the resulting system allowed the reproduction of neoplastic lesions in vitro at 27 days post-infection (PI), providing new evidence of the role of the parasite in the induction of carcinogenesis. This promising model could facilitate the study of host-pathogen interactions and the investigation of the process involved in Cryptosporidium-induced cell transformation.

Prostate contours delineation using interactive directional active contours model and parametric shape prior model.

Prostate contours delineation on Magnetic Resonance (MR) images is a challenging and important task in medical imaging with applications of guiding biopsy, surgery and therapy. While a fully automated method is highly desired for this application, it can be a very difficult task due to the structure and surrounding tissues of the prostate gland. Traditional active contours-based delineation algorithms are typically quite successful for piecewise constant images. Nevertheless, when MR images have diffuse edges or multiple similar objects (e.g. bladder close to prostate) within close proximity, such approaches have proven to be unsuccessful. In order to mitigate these problems, we proposed a new framework for bi-stage contours delineation algorithm based on directional active contours (DAC) incorporating prior knowledge of the prostate shape. We first explicitly addressed the prostate contour delineation problem based on fast globally DAC that incorporates both statistical and parametric shape prior model. In doing so, we were able to exploit the global aspects of contour delineation problem by incorporating a user feedback in contours delineation process where it is shown that only a small amount of user input can sometimes resolve ambiguous scenarios raised by DAC. In addition, once the prostate contours have been delineated, a cost functional is designed to incorporate both user feedback interaction and the parametric shape prior model. Using data from publicly available prostate MR datasets, which includes several challenging clinical datasets, we highlighted the effectiveness and the capability of the proposed algorithm. Besides, the algorithm has been compared with several state-of-the-art methods.

Angiographic regression patterns after intravitreal ranibizumab injections for neovascular age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To investigate the relation between visual gain, injection frequency, and the angiographic regression patterns after intravitreal ranibizumab on an as-needed basis in exudative age-related macular degeneration (AMD). PATIENTS AND METHODS: Fifty-nine treatment-naïve patients (68 eyes) were retrospectively analyzed. All patients received three consecutive monthly injections (induction phase) of ranibizumab (0.5 mg/0.05 mL). Based on fluorescein angiography (FA), the choroidal neovascularization (CNV) was judged to present either complete regression (pattern 1), partial regression (pattern 2), stabilization of the lesion size without leakage (pattern 3), stabilization of the lesion size with persistence of leakage (pattern 4), or increased angiographic size (pattern 5). RESULTS: Mean visual acuity (VA) significantly improved from 48 to 54.3 letters at 1 year after a mean of 5.5 injections (P < .001). Multiple linear regression revealed baseline VA as a predictor of visual gain and the angiographic pattern as a predictor of number of injections. Analysis of variance revealed a significant interaction (F-test [1.67] = 25, P < .001) between the number of injections at 12 months and the regression patterns, as evaluated by FA 1 month after the induction phase. Eyes showing complete CNV regression needed significantly fewer injections than eyes without any angiographic sign of CNV regression (3.4 injections in pattern 1 vs 5.6 injections in pattern 3 [P = .03], and 7 injections in pattern 4 [P < .001], 4.4 injections in pattern 2 vs 7 injections in pattern 4 [P < .001]). CONCLUSION: FA may represent a useful tool to adapt the rhythm of visits and intravitreal anti-vascular endothelial growth factor injections in exudative AMD.

Factors of accuracy of transient elastography (fibroscan) for the diagnosis of liver fibrosis in chronic hepatitis C.

UNLABELLED: The purpose of this study was to assess the influence of success rate and interquartile range on the accuracy of transient elastography for the diagnostic of fibrosis in hepatitis C virus infection. Two-hundred fifty-four consecutive patients had liver stiffness measurements and liver biopsy of at least 15 mm. Discordances of at least two stages between transient elastography and histological assessment were observed in 28 cases (11%). Factors of discordance were assessed by comparing the 28 misclassified cases with the 226 others. In multivariate analysis, fibrosis stage (F0-F2 versus F3-F4) and the ratio interquartile range/median value of liver stiffness measurement (IQR/M) were associated with discordances (P or= 0.21, discordances of at least two stages of fibrosis were respectively observed in 10 of 135 cases (7.4%) versus 18 of 119 cases (15.1%) (P or= 0.21 versus IQR/M < 0.21, for the diagnosis of liver fibrosis F >or= 2, F >or= 3, F = 4, areas under the receiver operating characteristic curve (AUROCs) were 0.80 (95% confidence interval [CI], 0.73-0.89) versus 0.81 (95% CI, 0.70-0.90), (P = NS); 0.80 (95% CI, 0.72-0.88) versus 0.89 (95% CI, 0.83-0.95) (P = 0.04); and 0.86 (95% CI, 0.77-0.94) versus 0.95 (95% CI, 0.92-0.99) (P = NS). No association was found between success rate and discordance. CONCLUSION: IQR/M is a factor of overestimation of liver fibrosis, and the most discriminant cutoff value is 0.21. Success rate is not a factor of accuracy for the diagnosis of hepatic fibrosis.

Routine practice HCV infection screening with saliva samples: multicentric study in an intravenous drug user population.

OBJECTIVE: The purpose of this randomized multicentric study was to evaluate the diagnostic contribution of screening for HCV infection on saliva samples in day-to-day practice in the intravenous drug-user (IVDU) population. METHODS: Between January and May 2004, 274 presumably HCV-negative IVDU were screened for HCV infection in 15 centers in France (median age 29 years). After centralized randomization, screening tests were performed on blood samples (arm A) or saliva samples (arm B). Screening tests were performed in 78 subjects (28%) had never been screened before and in 196 subjects (72%) who had had a negative HCV screening test on average 12 months prior to the beginning of the study. In the event of a positive saliva test for anti-HCV Ab, a serum test for anti-HCV Ab was performed. In the event of a positive serum test for anti-HCV Ab, PCR was performed on serum to measure HCV-RNA. RESULTS: Fourteen individuals were positive for HCV RNA (7 in each arm). Six of these cases had not been detected before. In eight cases, the median time between the last negative screening test and study inclusion was 11 months (range 6-94 months). CONCLUSIONS: Viremia tests were positive in 5% percent of the target population, although one-third of the individuals in arm A (blood samples) were not tested. The saliva test may be a useful alternative in the event of refusal of a blood test or when poor venous conditions compromise venous puncture. A confirmatory blood test still remains difficult to obtain in nearly half of patients.

An analysis of the biochemical diagnosis of 66 pheochromocytomas.

OBJECTIVES: The aims of this study were to determine the performance of each variable, to define the optimal diagnostic thresholds and to determine the relative value of assaying chromogranin A (CgA). DESIGN: Prospective study. METHODS: Two groups of patients were studied: a control group of 71 patients and a group of 63 patients with a histologically-proven pheochromocytoma (52 pheochromocytomas and 14 paragangliomas). Fourteen of the patients had a family history of the disease. Eleven variables were assayed in each patient, i.e. the plasma and urinary concentrations of amines and their derivatives, and the CgA serum concentration. RESULTS: The study of the control group showed that all the serum assays gave false positive results (from 6 to 23%), as did four of the six urinary assays (from 2.9 to 12.3%). The areas under the receiver operating characteristic curves varied from 0.689 to 0.992. The variables relating to the epinephrine pathway were significantly less expressed in the hereditary diseases than in the sporadic cases. The diagnostic thresholds of the three most efficient variables have been raised. CONCLUSIONS: Plasma determinations of metanephrines are now an easy and convenient tool for the diagnosis of pheochromocytoma. However, in our study the best specificity was obtained with the urinary tests rather than with the plasma assays while the highest sensitivities were for the normetanephrine assays. The assay of CgA was highly efficient in diagnosing pheochromocytomas in the absence of renal insufficiency. By combining it with fractionated metanephrine assays, the sensitivities of the latter were increased.