Images in Clinical Urology: Complex open pyeloplasty in a pelvic kidney

A pelvic kidney occurs in between 1 in 2200 and 1 in 3000 people,1 due to failure of ascent during development. It is commonly asymptomatic and usually functions normally. Pelvic ureteral junction obstruction can either be congenital or acquired, and is characterized by intrinsic stenosis or extrinsic compression of the ureter at the junction with the pelvicalyceal renal system. This can cause symptomatic or asymptomatic hydronephrosis. We describe the complex case and management of a patient with a massive pelvic ureteral junction obstruction in a pelvic kidney

A survival analysis of ventricular access devices for delivery of cerliponase alfa

OBJECTIVE: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare autosomal recessive disease caused by tripeptidyl peptidase 1 enzyme deficiency. At the authors' center, the medication cerliponase alfa is administered every 2 weeks via the intracerebroventricular (ICV) route. This requires the placement of a ventricular access device (VAD) or reservoir and frequent percutaneous punctures of this device over the child's lifetime. In this study, the authors audited the longevity and survival of these VADs and examined the causes of device failure. METHODS: A single-center survival analysis of VAD insertions and revisions (January 2014 through June 2020) was conducted. All children received cerliponase alfa infusions through a VAD. Patient characteristics and complications were determined from a prospectively maintained surgical database and patient records. For the VAD survival analysis, the defined endpoint was when the device was removed or changed. Reservoir survival was assessed using Kaplan-Meier curves and the log-rank (Cox-Mantel) test. RESULTS: A total of 17 patients had VADs inserted for drug delivery; median (range) age at first surgery was 4 years 4 months (1 year 8 months to 15 years). Twenty-six VAD operations (17 primary insertions and 9 revisions) were required among these 17 patients. Twelve VAD operations had an associated complication, including CSF infection (n = 6) with Propionibacterium and Staphylococcus species being the most prevalent organisms, significant surgical site swelling preventing infusion (n = 3), leakage/wound breakdown (n = 2), and catheter obstruction (n = 1). There were no complications or deaths associated with VAD insertion. The median (interquartile range) number of punctures was 59.5 (7.5-82.0) for unrevised VADs (n = 17) versus 2 (6-87.5) for revised VADs (n = 9) (p = 0.70). The median survival was 301 days for revisional reservoirs (n = 9) versus 2317 days for primary inserted reservoirs (n = 17) (p = 0.019). CONCLUSIONS: In the context of the current interest in intrathecal drug delivery for rare metabolic disorders, the need for VADs is likely to increase. Auditing the medium- to long-term outcomes associated with these devices will hopefully result in their wider application and may have potential implications on the development of new VAD technologies. These results could also be used to counsel parents prior to commencement of therapy and VAD implantation

Intercomparison of tritium and noble gases analyses, 3H/3He ages and derived parameters excess air and recharge temperature

International audienceGroundwater age dating with the tritium-helium (3H/3He) method has become a powerful tool for hydrogeologists. The uncertainty of the apparent 3H/3He age depends on the analytical precision of the 3H measurement and the uncertainty of the tritiogenic 3He component. The goal of this study, as part of the groundwater age-dating interlaboratory comparison exercise, was to quantify the analytical uncertainty of the 3H and noble gas measurements and to assess whether they meet the requirements for 3H/3He dating and noble gas paleotemperature reconstruction. Samples for the groundwater dating intercomparison exercise were collected on 1 February, 2012, from three previously studied wells in the Paris Basin (France). Fourteen laboratories participated in the intercomparison for tritium analyses and ten laboratories participated in the noble gas intercomparison. Not all laboratories analyzed samples from every borehole. The reproducibility of the tritium measurements was 13.5%. The reproducibility of the 3He/4He ratio and 4He, Ne, Ar, Kr and Xe concentrations was 1.4%, 1.8%, 1.5%, 2.2%, 2.9%, and 2.4% respectively. The uncertainty of the tritium and noble gas measurements results in a typical 3H/3He age precision of better than 2.5 years in this case. However, the measurement uncertainties for the noble gas concentrations are insufficient to distinguish the appropriate excess air model if the measured helium concentration is not included. While the analytical uncertainty introduces an unavoidable source of uncertainty in the 3H/3He apparent age estimate, other sources of uncertainty are often much greater and less well defined than the analytical uncertainty

Separate episodes of capillary leak syndrome and pulmonary hypertension after adjuvant gemcitabine and three years later after nab-paclitaxel for metastatic disease

Background: Systemic capillary leak syndrome is a rare disease with a high mortality rate. This syndrome is characterised by generalised edema, hypotension, hemoconcentration, and hypoproteinemia. The cause is the sudden onset of capillary hyperpermeability with extravasations of plasma from the intravascular to the extravascular compartment. We present the case of a patient who experienced two episodes of systemic capillary leak syndrome and pulmonary hypertension; the first after gemcitabine in an adjuvant setting and the second three years later after treatment with nab-paclitaxel for metastatic disease.Case presentation: A 65-year-old patient underwent a pancreatectomy in January 2010 for ductal carcinoma (pT3 N0 M0, stage IIa), followed by adjuvant chemotherapy. Seven days after the last cycle, she developed dyspnea associated with orthopnea and cough. A transthoracic cardiac ecocolordoppler was performed, with evidence of pulmonary hypertension (58 mmHg). Blood tests showed an increase in creatinine, pro-BNP and D-Dimer. She began high-dose diuretic therapy combined with cortisone. After a month, the patient was eupneic and the anasarca had resolved. We decided gradually to reduce the steroid and diuretic therapy. After ten days of the reduction, the patient began to re-present the same symptoms after treatment with gemcitabine. Corticosteroid therapy was restored with rapid clinical benefit and decreased pro-BNP after a week of treatment. After two years, the disease returned. As a first line treatment, it was decided to use nab-paclitaxel 100 mg/m2 weekly. After two doses, followed by approximately 14 days of treatment, the patient developed acute respiratory distress syndrome. The clinical suspicion was a relapse of capillary leak syndrome and treatment with a high-dose diuretic (furosemide 250 mg daily) was started combined with cortisone (40 mg methylprednisolone). The patient showed a progressive clinical benefit.Conclusions: In patients treated with gemcitabine and nab-paclitaxel who experience a sudden onset of diffuse edema with respiratory distress, capillary leak syndrome should be suspected. Immediate treatment with corticosteroids may be life-saving. © 2013 Casadei Gardini et al.; licensee BioMed Central Ltd

Tobacco-specific and combustion pollutants in settled house dust in Malta

Aim: Most of the carcinogenic pollutants coming from tobacco smoking or other combustion processes tend to accumulate in settled house dust (SHD) over time. This study evaluated the load of these pollutants in smokers and non-smokers’ houses from relatively fresh SHD collected in five different districts on the island of Malta. Methods: An improved, efficient extraction method to obtain three fractions from a 200 mg of SHD was developed. It was validated for the analysis of nicotine and polycyclic aromatic hydrocarbons (PAH) by GCMS/ MS and nicotelline and TSNA by LC-MS/MS. Kruskal-Wallis H tests were used to evaluate differences across districts, while a Mann-Whitney U test was used to check differences between smokers and non-smokers’ houses. Diagnostic ratios were used to evaluate the carcinogenicity of PAH in SHD in Malta. Results: For all analytes, no statistical difference was observed across different districts, but, in smokers’ houses, 97.9% of the total concentration of all target analytes found in SHD is nicotine, 0.1% is TSNA, and 2.0% is PAH. In non-smokers’ houses, nicotine represents 16.8% of the load, while 0.4% and 82.8% are TSNA and PAH, respectively. The carcinogenicity of the PAH mixture in Maltese SHD, expressed as the mean benzo(a)pyrene equivalent (BaPeq) is 371 ng/g. Conclusion: Indoor activities, ventilation practices, and infiltration of outdoor pollutants contribute to a complex SHD composition. Although the BaPeq is on the lower end of carcinogenicity, the effects of a mixture including tobacco-related potent carcinogens in SHD are largely unknown. In view of indoor, continuous exposure to SHD through several pathways, further research is warranted.peer-reviewe

Origin of fluids and related barite deposits at vent sites along the Peru convergent margin

The venting at the northern Peru convergent margin, unlike at other margins, has produced large barite deposits, which have not been observed outside the vents. The 87Sr/86Sr isotopic ratios of the fluids are more radiogenic than seawater. To explain these elevated values, we propose either the influence of a fluid characterized by a more radiogenic signature originating from the continent, or a reaction between seawater and the underlying continental metamorphic basement. The presence of this nonlocal radiogenic component is marked more strongly on the 87Sr/86Sr ratios measured in the barite deposits. We assume that the fluid sampled at the venting site and the fluid responsible for the barite deposit sampled at the same site originated from the same source, i.e., the Paleozoic metamorphic basement of the Andean continental margin

The trajectory taken by dimeric Cu/Zn superoxide dismutase through the protein unfolding and dissociation landscape is modulated by salt-bridge formation

Native mass spectrometry (MS) is a powerful means for studying macromolecular protein assemblies, including accessing activated states. However, much remains to be understood about what governs which regions of the protein (un)folding funnel are explored by activation of protein ions in vacuum. Here we examine the trajectory that Cu/Zn superoxide dismutase (SOD1) dimers take over the unfolding and dissociation free energy landscape in vacuum. We examined wild-type SOD1 and six disease-related point-mutants by using tandem MS and ion-mobility MS as a function of collisional activation. For six of the seven SOD1 variants, increasing activation prompted dimers to transition through two unfolding events and dissociate symmetrically into monomers with (as near as possible) equal charges. The exception was G37R, which proceeded only through the first unfolding transition, and displayed a much higher abundance of asymmetric products. Supported by the observation that ejected asymmetric G37R monomers were more compact than symmetric G37R ones, we localised this effect to the formation of a gas-phase salt-bridge in the first activated conformation. To examine the data quantitatively, we applied Arrhenius-type analysis to estimate the barriers on the corresponding free energy landscape. This reveals a heightening of the barrier to unfolding in G37R >5 kJmol-1 over the other variants, consistent with expectations for the strength of a salt-bridge. Our work demonstrates weaknesses in the simple general framework for understanding protein complex dissociation in vacuum, and highlights the importance of individual residues, their local environment, and specific interactions in governing product formation

International forum. an investigation of iron status in blood donors

No abstract availabl