Diagnosis and management of upper tract urothelial carcinoma.

Urothelial carcinoma of the upper urinary tract (UTUC) is a rare disease, comprising only 5-10% of all urothelial malignancies. There is a paucity of high level evidence to guide treatment decisions due to the rarity of the disease. Through the creation of multi-institutional collaborations in recent years, our understanding of the natural history of UTUC and treatment algorithms has improved. However, our understanding of UTUC is mostly driven by extrapolation of findings and paradigms of urothelial carcinoma of the urinary bladder. With current imaging techniques and biopsy modalities, accurate diagnosis and staging remains difficult for this disease and prognostic models are limited in their ability to predict clinical outcomes. As such, over or under-treatment is common, highlighting the need for individualized treatment regimens which often require a multimodal approach. Endoscopic or radical resection represent the mainstays of treatment, while the role of intraluminal agents and systemic chemotherapy is yet to be clearly defined. Herein we review current concepts and management strategies as well as recent developments in UTUC.

Biochemical, molecular, and virulence characteristics of select Mycobacterium marinum isolates in hybrid striped bass Morone chrysops x M. saxatilis and zebrafish Danio rerio.

A panel of 15 Mycobacterium marinum isolates was characterized by biochemical tests, sequencing the ribosomal DNA intergenic spacer (ITS) region and the heat shock protein 65 gene (hsp65) and pulsed-field gel electrophoresis (PFGE). The biochemical characteristics of all isolates were similar, except for Tween 80 hydrolysis. DNA sequence of hsp65 for a subset of isolates were identical; however, at position 5 of the ITS rDNA, a single nucleotide polymorphism was identified. Isolates possessing a guanine residue at this position (G strains) were unable to hydrolyze Tween 80, while isolates that contained an adenine residue at this position (A strains) were positive for Tween 80 hydrolysis. PFGE successfully discriminated between the G and A strains; all G strains had identical AseI restriction enzyme-cutting patterns while the A strains exhibited a variety of cutting patterns. Eight isolates (4 G and 4 A strains) were further characterized for virulence by experimental infection of hybrid striped bass (HSB) Morone chrysops x M. saxatilis and zebrafish Danio rerio. Seven of the 8 strains produced cumulative mortality ranging from 13.3 to 83.3% in the HSB virulence trial. The M. marinum reference strain ATCC 927T did not produce mortality in HSB. HSB exposed to the G strains had significantly higher cumulative mortality than those exposed to the A strains. When these same isolates were tested in zebrafish, 6 of the 8 strains caused 100% cumulative mortality, with 2 of the A strains being the most pathogenic. In zebrafish, however, ATCC 927T was virulent and produced 28.5% mortality. Collectively, we conclude that the M. marinum G strains are unique and may represent a distinct virulence phenotype in HSB, but this trend was not consistent in zebrafish.

Media reporting of ProtecT: a disconnect in information dissemination?

BACKGROUND: Given the central role of the media in disseminating information to the public, we analyzed news coverage of the recent publication from ProtecT to assess views on treatment, the level of detail presented and degree of bias. METHODS: We applied a predefined search strategy to identify all news articles reporting on ProtecT within 30 days of its publication. Articles were independently assessed by two urologists and two lay persons using five-point Likert scales. Descriptive statistics and analysis of variance were used. RESULTS: Of 33 unique articles identified, 20 (61%) conveyed negative views on definitive treatment for localized prostate cancer (PCa), while 29 (88%) expressed favorable views of active surveillance/monitoring (AM). Nevertheless, fewer than half of the articles described what AM entails (n=15; 46%) or the rate of treatment in the AM arm (n=12; 36%). Moreover, while 32 (97%) articles highlighted the absence of a difference in cancer-specific mortality at 10 years, only 17 (52%) mentioned the need for longer follow-up. A total of 17 (52%) articles had a notable degree of perceived bias (⩾4/5 on Likert scale), with shorter articles (P=0.02), articles covering few content areas (P=0.03) and articles that did not detail what AM entails (P=0.003) containing significantly increased bias. CONCLUSIONS: The majority of news articles regarding ProtecT presented an adverse view of definitive treatment for localized PCa relative to AM, but failed to highlight key nuances of the trial. Healthcare professionals and the lay public should be cautious in acquiring medical news through the general media. Additionally, the urologic community must continue to improve the quality of disseminated information, for example, through proactively engaging with the media, through social media and/or through participation in continuing education lecture series, so as to guide the knowledge translation process, especially upon publication of such potentially influential studies.

Aquatic Francisella-like bacterium associated with mortality of intensively cultured hybrid striped bass Morone chrysops x M. saxatilis.

The present study identifies an emerging disease associated with an aquatic Francisella-like bacterium that can cause mortality in hybrid striped bass Morone chrysops x M. saxatilis reared intensively in freshwater. Clinically affected fish were lethargic, had scattered haemorrhagic cutaneous lesions and diffuse gill pallor. The head kidney and spleen were markedly swollen and contained numerous interstitial granulomas; histological examination revealed small, pleomorphic Gram-negative coccobacilli within vacuolated cells. The bacterium could not be cultured from head kidney homogenates either with standard or enriched microbiological media or following inoculation of a Chinook salmon embryo (CHSE)-214 cell line. No amplification product was obtained from head kidney DNA by polymerase chain reaction (PCR) assay using Piscirickettsia salmonis-specific primers. PCR analysis of infected head kidney homogenate with primers designed for the eubacterial 16S rRNA produced a single amplicon. Phylogenetic analysis of this DNA sequence demonstrated that the sequence aligned most closely with members of the genus Francisella, identified from tilapia Oreochromis spp. in Taiwan and an aquatic Francisella species that was recently isolated from the three-line grunt Parapristipoma trilineatum in Japan. This Francisella-like disease was transmitted to naive hybrid striped bass fingerlings by intraperitoneal injection of tissue homogenates prepared from a natural outbreak. All fish developed gross and histological lesions identical to those from natural outbreaks. Intracellular Gram-negative bacteria were observed within the cytoplasm of cells (presumably macrophages) within the granulomas, but bacteria were not recovered. The 16S DNA sequence of the bacterium obtained from tissues of experimentally infected fish was identical to that obtained from the fish used as infected donor tissue.

Structural analysis of glycosyl-phosphatidylinositol antigens of Leishmania major.

Three glycosyl-phosphatidylinositol glycolipids recognized by antibodies from patients with cutaneous leishmaniasis were extracted from Leishmania major promastigotes by hexane:isopropanol and then purified by thin layer chromatography and LH-20 gel chromatography. Structural analysis was carried out using chemical analyses, fast atom bombardment mass spectrometry, and 1H NMR. The major structures deduced can be summarized as follows: (formula: see text) where n = 0, 1, 2; R1 = (CH2)23-CH3; R2 = (CH2)14-CH3 or (CH2)16-CH3. Alkyl-acyl substitutions in the glycerol backbone showed considerable heterogeneity. These three glycolipids belong to a relatively new class of compounds and may represent sequential steps in the biosynthesis of glycosyl-phosphatidylinositols which anchor proteins or other glycoconjugates to Leishmania cell membranes.

Screening for reproductive toxicity in Fundulus heteroclitus by genetic expression profiling.

Abstract Potentially teratogenic agents enter the environment at a rate that greatly exceeds current capabilities to effectively evaluate their reproductive toxicities. This is due, in part, to costly, labour-intensive methodologies involving mammalian embryonic screening assays that are currently in use worldwide. Therefore, we sought to develop a rapid, less expensive screening system with which to identify molecular biomarkers of teratogenicity using a non-mammalian system. Embryos of the topminnow, Fundulus heteroclitus, offer several advantages in terms of reproductive toxicity screening efficiency as compared with mammalian embryonic systems. These embryos are easily manipulated and develop normally at ambient temperature in air, water, or air-saturated mineral oils, making them readily adapted for field studies. In the present study, developing f. heteroclhs embryos were exposed to teratogenic concentrations of sodium valproate (VPA) or arsenic acid (arsenate), and the frequency and types of induced malformations were evaluated. Using in situ transcription and antisense RNA (aRNA) amplification procedures (IST/aRNA), we attempted to correlate the teratogenic outcomes to specific alterations in the expression of a panel of developmentally regulated genes. Preliminary studies identified treatment concentrations of arsenate and VPA that induced abnormal development in 95 % of the surviving embryos. Among the F. heteroclitus embryos, the structural defects most commonly induced by these compounds were cardiac and neural tube malformations. The genetic expression profiles revealed a number of genes whose expression levels were significantly altered by exposure to the test compounds. Molecular analysis of f. heteroclitus embryonic development represents a novel, inexpensive approach to screen for potential teratogens, and identify genes whose expression patterns may be used as biomarkers, or indicators, of teratogenicity.