Low pressure radiofrequency balloon angioplasty: Evaluation in porcine peripheral arteries

AbstractObjectives. The purpose of this study was to evaluate the efficacy of radiofrequency-powered thermal balloon angioplasty in an in vivo porcine model.Background. Various modes of thermal energy used adjunctively during balloon angioplasty have demonstrated the potential to enhance the results of acute lumen dilation.Methods. In normal pigs, 75 peripheral arteries were dilated with a newly designed, radiofrequency-powered, thermal angioplasty balloon. All inflations were performed at 2-atm pressure for 85 s. Dilations were performed either with (hot) or without (cold) the application of heat. Lumen dimensions and vessel morphology were assessed with intravascular ultrasonography. At the end of each study, dilated arterial segments were harvested for histologic examination.Results. Single cold balloon inflations resulted in a 12.7% increase in arterial cross-sectional area whereas single hot inflations resulted in a 22.9% increase (p < 0.03). Similarly, when multiple cold inflations were compared with multiple hot inflations, two, three and four sequential hot inflations resulted in a significantly greater increase in cross-sectional area than an equivalent number of cold inflations (p < 0.03).Histologic examination demonstrated a temperaturedependent effect on the depth of medial necrosis and extent of arterial wall thinning (p < 0.001) as well as evidence for uniform alteration of elastic tissue fibers at temperatures of ≥60 °C (p < 0.03).Conclusions. Low pressure radiofrequency thermal balloon angioplasty results in a greater increase in cross-sectional area in porcine peripheral arteries than does nonheated conventional balloon angioplasty. The pathologic basis for this enhanced dilation may be a temperature-dependent effect on medial necrosis, thinning of the arterial wall or alteration of vascular elastic fibers, alone or in combination

A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPreviously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.info:eu-repo/grantAgreement/EC/FP7/21807

Quimbaya culture artefacts, Museo del Oro, Bogota, Colombia, 1977, [3] [picture] /

Condition: Good.; Title devised by cataloguer based on inscription on reverse.; Part of Wolfgang Sievers photographic archive.; Sievers number: EK-4560-add25 (devised number).; Inscriptions: "Quimbaya-CQ-38".; Also available in an electronic version via the Internet at: http://nla.gov.au/nla.pic-vn4189676

Increased substance P responses in dorsal root ganglia and intestinal macrophages during Clostridium difficile toxin A enteritis in rats

Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of toxin A into rat ileum causes a rapid increase in SP content in lumbar dorsal root ganglia (DRG) and mucosal scrapings 30–60 min after toxin A administration. Toxin A-mediated fluid secretion, mannitol permeability, and ileal histologic damage is significantly increased only after 2 hr. Toxin A also causes an increase in the abundance of SP mRNA in lumbar DRG and ileal mucosa as measured by reverse transcription–PCR. Lamina propria macrophages (LPMs) obtained from toxin A-injected loops release greater amounts of tumor necrosis factor α (TNFα) and SP as compared with LPMs isolated from buffer-injected loops (P < 0.01). Pretreatment of rats with the SP antagonist CP-96,345 inhibits toxin A-mediated TNFα release from isolated LPMs, whereas an inactive enantiomer (CP-96,344) of the SP antagonist has no effect. LPMs obtained from toxin A-injected ileal loops incubated in vitro with SP (10(−8) to 10(−9) M) show enhanced TNFα secretion, whereas LPMs isolated from buffer-injected loops do not respond to SP. In addition, LPMs obtained from toxin A-injected ileal loops incubated in vitro with CP-96,345 showed a diminished TNFα release. Our results indicate that activated LPMs secrete SP during toxin A enteritis that can lead to secretion of cytokines, suggesting an autocrine/paracrine regulation of cytokine secretion by SP from LPMs during intestinal inflammation

Genome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer

Genome-wide association studies (GWAS) of urinary bladder cancer (UBC) have yielded common variants at 12 loci that associate with risk of the disease. We report here the results of a GWAS of UBC including 1670 UBC cases and 90 180 controls, followed by replication analysis in additional 5266 UBC cases and 10 456 controls. We tested a dataset containing 34.2 million variants, generated by imputation based on whole-genome sequencing of 2230 Icelanders. Several correlated variants at 20p12, represented by rs62185668, show genome-wide significant association with UBC after combining discovery and replication results (OR = 1.19, P = 1.5 × 10(-11) for rs62185668-A, minor allele frequency = 23.6%). The variants are located in a non-coding region approximately 300 kb upstream from the JAG1 gene, an important component of the Notch signaling pathways that may be oncogenic or tumor suppressive in several forms of cancer. Our results add to the growing number of UBC risk variants discovered through GWAS

Sequence variant on 8q24 confers susceptibility to urinary bladder cancer.

Contains fulltext : 71044.pdf (publisher's version ) (Closed access)We conducted a genome-wide SNP association study on 1,803 urinary bladder cancer (UBC) cases and 34,336 controls from Iceland and The Netherlands and follow up studies in seven additional case-control groups (2,165 cases and 3,800 controls). The strongest association was observed with allele T of rs9642880 on chromosome 8q24, 30 kb upstream of MYC (allele-specific odds ratio (OR) = 1.22; P = 9.34 x 10(-12)). Approximately 20% of individuals of European ancestry are homozygous for rs9642880[T], and their estimated risk of developing UBC is 1.49 times that of noncarriers. No association was observed between UBC and the four 8q24 variants previously associated with prostate, colorectal and breast cancers, nor did rs9642880 associate with any of these three cancers. A weaker signal, but nonetheless of genome-wide significance, was captured by rs710521[A] located near TP63 on chromosome 3q28 (allele-specific OR = 1.19; P = 1. 15 x 10(-7))

European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene

Contains fulltext : 97884.pdf (publisher's version ) (Closed access)Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 x 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC