An unusual case of intrarenal coiled and ruptured guidewire.

OBJECTIVE: To the best of our knowledge there are only 3 reports of fractured guidewires inside the pelvicalyceal system, successfully removed with endourology techniques, and this is the first one presenting a tightly coiled intraparenchymal section. MATERIAL AND METHODS: A 59-year-old woman was hospitalized for surgical treatment of a right kidney of reduced size. Past history revealed pyelolithotomy for a staghorn stone 14 months earlier at another Institution with subsequent ureteral obstruction, one failed attempt at ureteral double-J catheter insertion and one failed attempt at percutaneous nephrostomy placement 5 months postoperatively. Another nephrostomy was placed, but left indwelling briefly. CT scan demonstrated a small-size kidney with residual stone fragments and presence of a "device" in the lower pole. The tapered distal extremity of an hydrophilic guidewire, with a tightly coiled central section wedged in the renal tissue was found inside the nephrectomy specimen. RESULTS: While the Radiologist who read the CT scan hypothesized that the "device" was a fragment of double-J ureteral stent or nephrostomy catheter, it consisted of the hydrophilic extremity of a guidewire, broken during a previous attempt at nephrostomy placement. Perirenal fibrosis and inappropriate angle between the needle and the lower calyx are the likely causes of guidewire coiling during its advancement and subsequent rupture during withdrawal. CONCLUSIONS: Urologists must be aware that, although percutaneous nephrostomy has a very high technical success rate, unusual complications like guidewire fracture may occur, and that modern imaging techniques can provide an accurate picture of this condition.

Delayed-onset ureteral lesions due to thermal energy: an emerging condition.

OBJECTIVES: To describe the risks of ureteral damage occurring during urological and gynecological procedures utilizing energybased surgical devices (ESD) during both laparoscopic and open procedures. MATERIALS AND METHODS: During the last 20 months we observed five cases of iatrogenic ureteral lesions caused by ESD which required open surgery. There were 3 lesions of the lower ureter occurring during gynecological laparoscopic or robotic procedures, and 2 lesions of the upper ureter occurring during open enucleation of low-stage renal cell carcinomas. RESULTS: In the laparoscopic gynecological lesions the cause was attributable to monopolar cutting and bipolar coagulation: they presented with urine extravasation after 20, 15 and 15 days respectively and required ureteral reimplantation in 2 out of 3 cases. In the upper ureteral lesions the causes were bipolar coagulation and LigaSure Impact TM used for perirenal fat dissection: they presented after 2 and 4 months respectively and required uretero-ureterostomy and inferior nephropexy in one case and nephrectomy in the other. In 3 out of 5 cases there was an unsuccessful attempt at placing an ureteral double J stent, and in the 2 cases where it was placed it did not prevent the formation of subsequent stricture in one. CONCLUSIONS: The widespread diffusion of ESD has the potential drawback of inadvertent thermal energy transmission to the ureter. Delayed presentation of ureteral lesions and difficulties in ureteral stent placement were the common features of the cases observed. Inadvertent ureteral damage by different thermal energy sources is an emerging condition, requiring awareness, prompt recognition and adequate treatment with the reconstructive urology principles.

Drug delivery research in the European Union's Seventh Framework Programme for Research.

This paper presents an overview of drug delivery research activities funded by the European Union's Seventh Framework Programme for Research and Technological Development (FP7). It gives a brief introduction of the main policies, structure and budget of FP7 with the four Specific Programmes 'Cooperation', 'People', 'Ideas' and 'Capacities' including the ten priority themes of the Specific Programme Cooperation. The priority themes HEALTH, 'Information and Communication Technologies' (ICT) and 'Nanosciences and nanotechnologies, multifunctional Materials and Production technologies' (NMP) and the 'Innovative Medicines Initiative' (IMI) are discussed since they are the main sources of funding for medical and pharmaceutical research. Further details are provided on drug delivery research, notably the funding for development of drug delivery technologies by the NMP priority theme in the context of its funding of nanomedicine research projects. The link is made to the rapidly developing field of biomaterials research for implants and regenerative medicine. The paper highlights the strategic importance of the Key Emerging Technologies (KETs) including nanotechnology for the competitiveness of the medical and pharmaceutical sectors. Finally, there is an outlook to the future Framework Programme for Research 'Horizon 2020'.

Polychlorinated trityl radicals for dynamic nuclear polarization: the role of chlorine nuclei.

Polychlorinated trityl radicals bearing carboxylate substituents are water soluble persistent radicals that can be used for dynamic nuclear polarization. In contrast to other trityl radicals, the polarization mechanism differs from the classical solid effect. DFT calculations performed to rationalize this behaviour support the hypothesis that polarization is transferred from the unpaired electron to chlorine nuclei and from these to carbon by spin diffusion. The marked differences observed between neutral and anionic forms of the radical will be discussed.

Hyperpolarized (13)C magnetic resonance detection of carboxypeptidase G2 activity.

Carboxypeptidase G2 (CPG2) is a bacterial enzyme that is currently employed in a range of targeted cancer chemotherapy strategies such as gene-directed enzyme prodrug therapy (GDEPT). Employing dynamic nuclear polarization (DNP) and natural abundance (13)C magnetic resonance spectroscopy (MRS), we observed the CPG2-mediated conversion of a novel hyperpolarized reporter probe 3,5-difluorobenzoyl-L-glutamic acid (3,5-DFBGlu) to 3,5-difluorobenzoic acid (3,5-DFBA) and L-glutamic acid (L-Glu) in vitro. Isotopic labeling of the relevant nuclei with (13)C in 3,5-DFBGlu or related substrates will yield a further factor of 100 increase in the signal-to-noise. We discuss the feasibility of translating these experiments to generate metabolic images of CPG2 activity in vivo.

[Laparoscopic approach in acute appendicitis: experience with 501 consecutive cases]. / Approccio laparoscopico nelle appendiciti acute: l'esperienza di 501 casi consecutivi.

Appendicitis is an acute disease requiring urgent surgical treatment. Acute appendicitis is the most common surgical emergency in children and young adults, with an incidence of about 100-140 cases per 100,000 people. In our study we analyse 501 consecutive appendectomies performed in our department. From June 2003 to December 2008 we performed 501 appendectomies, 287 in male and 214 in female patients. The average age was 27.99 years (range: from 4 to 94 years). We routinely perform a laparoscopic approach with a standard protocol for patient selection. Following a standard protocol, 429 patients were selected for the laparoscopic approach and 72 for an open appendectomy. In 411 patients (95.8%) the surgical procedure was completed in laparoscopy with a conversion rate of about 4.2% (18/429). The conversion rate in the simple appendectomy subgroup was 0.98%, as against about 12.1% in the complex appendectomy subgroup. The open appendectomy group comprised 72 patients, 27 patients treated with an open approach by choice, 26 for necessity and 19 for protocol violation. There were 9 post-appendectomy complications (2.1%) and 3 re-operations (0.5%); the mortality rate was nil. Although 20 years have passed since the first laparoscopic appendectomy, today it is still debated whether or not the laparoscopic approach is the correct surgical procedure for the treatment of acute appendicitis. Several studies have shown that laparoscopic appendectomy presents a number of advantages in terms of a shorter hospital stay, less postoperative pain and fewer wound infections. Some authors, however, have demonstrated that the laparoscopic approach for acute appendicitis is associated with increased operative times and risk of intra-abdominal abscesses (above all if the appendix is perforated). Our experience confirms that the routinely performed laparoscopic approach to treat acute appendicitis is associated with a low rate of abscess complications: in our series some of the complications could be attributed to the surgical learning curve.

Modulating the relaxivity of hyperpolarized substrates with gadolinium contrast agents.

Gadolinium contrast agents are known to affect the outer-sphere relaxivities of nuclei other than protons. We have investigated the heteronuclear relaxivities of four commercial gadolinium contrast agents (Magnevist, Omniscan, Dotarem and Gadovist) on the relaxation of (13)C in glycine, (13)C in pyruvate and (15)N in choline with long relaxation times. Marked differences in the relaxivities were found between different contrast agents and are attributed to electrostatic effects. This methodology may find applications in the field of hyperpolarized magnetic resonance and by way of example we show that injection of a bolus of contrast agent into an aqueous solution containing hyperpolarized (15)N labeled tetramethylammonium or (13)C labeled pyruvate leads to a predictable shortening of the lifetime of the hyperpolarized signal.

Modulation of choline kinase activity in human cancer cells observed by dynamic 31P NMR.

Choline metabolites are widely studied in cancer research as biomarkers of malignancy and as indicators of therapeutic response. However, endogenous phosphocholine levels are determined by a number of processes that confound the interpretation of these measurements, including membrane transport rates and a series of enzyme catalysed reactions in the Kennedy pathway. Employing a dynamic (31)P NMR assay that is specific to choline kinase (ChoK) we have measured the rates of this enzyme reaction in cell lysates of MDA-MB-231 breast, PC-3 prostate and HeLa cervical cancer cells and in solutions of purified human ChoK. The rates are sensitive to inhibition by hemicholinium-3 (HC-3), a competitive ChoK inhibitor, and to N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H-89), an agent commercialized as a specific cyclic-AMP-dependent protein kinase A (PKA) inhibitor.

Therapeutic target metabolism observed using hyperpolarized 15N choline.

Choline is a precursor of cellular phospholipid metabolism that provides Magnetic Resonance (MR) and Positron Emission Tomography (PET) biomarkers for cancer detection and response assessment. Employing Dynamic Nuclear Polarization we show that the MR signal of 15N in choline can be enhanced by at least 4 orders of magnitude with a relaxation time of ca. 4 min, providing a method to observe the action of choline kinase, an important target for novel cancer therapeutics.

Conformational exchange in pimonidazole--a hypoxia marker.

Pimonidazole is one of a series of nitroimidazole compounds that is widely used as a marker for qualitative and quantitative assessment of tumour hypoxia. We have observed a novel dynamic conformational exchange process in this molecule in aqueous solution. By a combination of 1H, 13C, two-dimensional 1H-1H EXchange SpectroscopY (EXSY) and spectral simulation, we unambiguously attribute the conformational exchange process to flipping of the six-membered heterocyclic ring.