Evaluation of the combination of endothelin receptor antagonists (ERA) and phosphodiesterase-5 inhibitors for the treatment of pulmonary arterial hypertension (PAH) in pathologic human pulmonary arteries in an ex-vivo organ bath model.

PURPOSE: Medical combination therapy of pulmonary arterial hypertension (PAH) may alleviate the drawbacks of monotherapy by avoiding drug tolerance and by increasing effectiveness, as shown by the combination of ambrisentan and tadalafil (AMBITION trial). The present ex-vivo study evaluated the combination of the endothelin receptor antagonists (ERA) macitentan and bosentan with the phosphodiesterase-5 (PDE-5) inhibitor vardenafil in pulmonary arteries from patients suffering from terminal lung disease as a model of PAH. METHODS: Segments of the pulmonary vessels were excised from resected lungs of patients requiring lung transplantation (LTX). Contraction of pulmonary arteries (PA) was elicited by consecutive dose-response curves of endothelin-1 (ET-1) followed by norepinephrine (NE) to allow inhibition by different pathways. Forces were measured isometrically in an organ bath in the presence and absence of ERA and PDE-5 inhibitors and their combination. RESULTS: PA of 38 patients were examined between October 2016 and November 2019. Bosentan (1E-7 M) and macitentan (1E-8 M, 3E-8 M, 1E-7 M) inhibited ET-1 induced contractions, whereas vardenafil (1E-6 M, 3E-6 M, 1E-5 M) inhibited only the NE induced part of the contractions. Vardenafil enhanced bosentan-induced inhibition of vasoconstriction in a dose-dependent fashion. Combination effects exceeded single bosentan at 3E-6 M and 1E-5 M vardenafil, and they exceeded single vardenafil at the lower vardenafil concentrations. Macitentan showed a more pronounced inhibition than bosentan regardless of the lower concentrations. Accordingly, combination effects with vardenafil resembled those of macitentan alone. CONCLUSIONS: Macitentan and bosentan were potent antagonists of vasoconstriction in PA of LTX patients. The benefit of drug combinations was demonstrated at selected concentrations only owing to a narrow therapeutic range of vardenafil in this ex-vivo model. These results suggest the utility of drug combinations other than the established pair of ambrisentan and tadalafil in PAH treatment but also make a case for a further assessment of vasodilator properties of drugs complementing ERA.

[Organ Bath Experiments on Human Pulmonary Vessels: Assessment of Drug Efficacy for Treatment of Pulmonary Arterial Hypertension]. / Organbadversuche an humanen Pulmonalgefäßen: Beurteilung der Medikamentenwirkung zur Behandlung der pulmonalarteriellen Hypertonie.

Various vasodilator medications are used in the treatment of pulmonary arterial hypertension (PAH), such as endothelin receptor antagonists (ERA) or phosphodiesterase-5-(PDE-5-)inhibitors. In a human ex vivo model, we investigated whether the combination of two substance classes could achieve a higher effect or - without loss of vasodilatation - a lower dosage of the individual substances might be sufficient. We established an ex vivo organ bath model to evaluate the dose-dependent effects of ERA and PDE-5-inhibitors on pulmonary vessels harvested from patients who underwent surgery (lung resection/transplantation). We compared the combined use of both substance classes with administration of one class of drugs alone. Due to the limitations of the experimental design, it is not possible to extrapolate our results to the conditions in vivo. Nevertheless, organ bath proved to be helpful in evaluating the dose-dependent effects of ERA and PDE-5 inhibitors, which is not practical in everyday clinical practice. In this setting, the effectiveness of the combination therapy and the potential for dose reduction depended on the concentrations used and on the influence of previous illnesses on blood vessel function. This article describes the most important results of our experimental investigations and suggestions for future projects.

Neglected nano-effects of nanoparticles in the interpretation of their toxicity.

Nanoparticles with smaller diameters have larger surface areas. Unfortunately, this fact is often neglected in their biomedical characterization, e.g. in the evaluation of their toxicity with cell viability tests. We here point out the different scientific conclusions drawn in such tests when considering the traditional mass or concentration of nanoparticles, or their surface areas.

Do time of birth, unit volume, and staff seniority affect neonatal outcome in deliveries at ≥34+0 weeks of gestation?

OBJECTIVE: We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation. DESIGN: Population-based prospective cohort study. SETTING: Ten public hospitals in the Austrian province of Styria. SAMPLE: A total of 87 065 neonates delivered in the period 2004-2015. METHODS: Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. MAIN OUTCOME MEASURES: Neonatal composite adverse and severely adverse outcome measures. RESULTS: The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. CONCLUSIONS: Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. TWEETABLE ABSTRACT: Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.

[A Rare Cause of a Spontaneous Pneumothorax]. / Seltene Ursache eines Spontanpneumothorax.

A young patient presented himself to the emergency department with sudden-onset, breathing-dependent right-sided thoracic pain. The auscultation revealed diminished breath sounds on the right. The radiograph showed a pneumothorax which was immediately dealt with chest tube drainage. The CT scan of the thorax showed minuscule subpleural bullae. Video-assisted thoracoscopic surgery (VATS) was performed due to persistent fistulae formation through the drain. The subpleural, bullous and emphysematous changes were histologically confirmed. Investigations into the cause showed evidence of alpha-1-antitrypsin deficiency (AATD). The patient is a Pi MZ type. Few cases of spontaneous pneumothorax as the first manifestation of alpha-1-antitrypsin deficiency have been described. Conclusion: When diagnosing primary spontaneous pneumothorax, alpha-1-antitrypsin deficiency should be considered.

Neuroendocrine profiles associated with discrete behavioural variation in Symphodus ocellatus, a species with male alternative reproductive tactics.

The molecular mechanisms underlying phenotypic plasticity are not well understood. Identifying mechanisms underlying alternative reproductive tactics (ARTs) in species for which the behavioural and fitness consequences of this variation are well characterized provides an opportunity to integrate evolutionary and mechanistic understanding of the maintenance of variation within populations. In the ocellated wrasse Symphodus ocellatus, the behavioural phenotypes of three distinct male morphs (sneakers, satellites and nesting males), which arise from a single genome, have been thoroughly characterized. To determine the neuroendocrine and genomic mechanisms associated with discrete phenotypic variation and ARTs in S. ocellatus in their natural environment, we constructed a whole-brain de novo transcriptome and compared global patterns of gene expression between sexes and male morphs. Next, we quantified circulating cortisol and 11-ketotestosterone (11-kt), mediators of male reproductive behaviours, as well as stress and gonadal steroid hormone receptor expression in the preoptic area, ventral subpallial division of the telencephalon and dorsolateral telencephalon, critical brain regions for social and reproductive behaviours. We found higher levels of 11-kt in nesting males and higher levels of cortisol in sneaker males relative to other male morphs and females. We also identified distinct patterns of brain region-specific hormone receptor expression between males such that most hormone receptors are more highly expressed in satellites and nesting males relative to sneakers and females. Our results establish the neuroendocrine and molecular mechanisms that underlie ARTs in the wild and provide a foundation for experimentally testing hypotheses about the relationship between neuromolecular processes and reproductive success.

[Decortication in Pleural Empyema: Reasonable Effects on Lung Function?]. / Dekortikation bei Pleuraempyem: funktionell sinnvoll?

UNLABELLED: Parapneumonic pleural effusion (PPE) occurring in early-stage (stage I) pleural empyema (PE) can be managed by chest tube drainage, which should be performed as soon as possible, to achieve re-expansion of the pulmonary parenchyma. Chronic disease leads to fibrin deposits on both pleural surfaces (stage II), followed by a thickened pleura peel (stage III). A trapped or compressed lung can only be released by surgical decortication, which may be performed with a minimally-invasive approach (video-assisted thoracoscopy) or an open technique (thoracotomy). This article reviews effects on pulmonary function after decortication in chronic empyema patients. MATERIAL AND METHODS: Selective literature research using Medline (key words: pleural empyema, decortication, lung function). A comparative analysis was performed on functional parameters obtained before and after surgical decortication in patients with chronic pleural empyema. RESULTS: Decortication in chronic PE significantly enhanced spirometric parameters (FEV1, VC/FVC) in all analysed studies. Considerable differences were observed regarding the mean follow-up time (early postoperative to several months after surgery). Computed tomography scans were usually analysed after a minimum of 6 months postoperatively. Measurements of anterior-posterior and transverse diameters as well as volume quantification of the operated and non-operated lung were performed in pre- and postoperative imaging. Statistical comparison revealed a significant decrease in thoracic asymmetry. In addition to static and dynamic pulmonary performance, pulmonary perfusion improved significantly after decortication as demonstrated by lung perfusion scans performed immediately after surgery and during a period of 7 to 10 months thereafter. CONCLUSION: Surgical decortication in chronic pleural empyema improves lung function and increases perfusion. Besides a significant enhancement of spirometric parameters, re-expansion of the diseased lung leads to equalisation of thoracic asymmetry and may even prevent loss of volume in the affected lung.

[Outcomes of Stage-Adapted Surgical Treatment of Pleural Empyema]. / Ergebnisse der stadienadaptierten chirurgischen Therapie von Pleuraempyemen.

BACKGROUND: The surgical treatment of pleural empyema should be carried out depending on the stage of the disease and the patient's symptoms. The aim of this study was to evaluate the outcomes of surgical pleural empyema treatment. PATIENTS AND METHODS: Retrospective analysis of all patients with pleural empyema treated surgically between January 2008 and December 2013. The primary endpoint of the study was inpatient lethality. Secondary endpoints included duration of inpatient stay, type of treatment (surgical/conservative), proof of pathogen and type, alteration and duration of antibiotic therapy. RESULTS: Of 359 patients, 0.8 % (n = 3) had stage I empyema, 50.4 % (n = 181) had stage II and 48.7 % (n = 175) had stage III. The most frequent causes (32.4 %) included acute pneumonia (parapneumonic pleural empyema), surgery (usually thoracic) in 18.0 % of cases and previous pneumonia (postpneumonic pleural empyema) in 15.4 %. Surgery was performed in 86 % of cases (operative procedures: open thoracotomy 85 %, VATS 15 %). The average duration of inpatient stay was 20 days for stages II and III. Recovery following VATS was significantly shorter in stage II compared to thoracotomy (p = 0.022). Hospital lethality amounted to 7.0 % (25 patients). The lethality rate was 5.5 % (10/185) in stage II and 8.6 % (15/175) in stage III. Patients with confirmed pathogens had a significantly worse mortality rate across all stages (9.8 %) than patients with no confirmed pathogens (4.0 %, p = 0.034). Age, malignant underlying disease, multiple comorbidities, immunosuppression, a change in antibiotic regimens and sepsis were significant risk factors. CONCLUSION: The inpatient lethality of patients with pleural empyema correlates with the stage of the condition. Positive confirmation of pathogens, sepsis, a higher age, multiple comorbidities, malignant tumour disease, immunosuppression and a change of antibiotics are negative prognostic factors.

Radiotherapy with soft X-rays in Dupuytren's disease - successful, well-tolerated and satisfying.

BACKGROUND: Up to present no curative treatment is known for Dupuytren's disease (DD). Surgery remains the most common treatment but lack of long-term efficacy and complications limit this therapeutic option. OBJECTIVE: In a retrospective analysis, the results of radiotherapy with soft X-rays in the treatment of DD were evaluated. METHODS: A total of 206 patients (297 affected hands) with DD were included. Radiation therapy was carried out with soft X-rays. A structured questionnaire considering patient and disease characteristics and effects of radiotherapy was evaluated after a median follow-up time of 40 months. RESULTS: Ninety-three (45%) of the 206 treated patients were reported on a regression of symptoms after radiation. No further disease progression (including patients with regression) was present in 165 patients (80%). Satisfaction with the therapy was expressed with an average score of 7.9 points (visual analogue scale, 0 = not satisfied, 10 = extremely satisfied). Subjective therapeutic effects for 426 nodules and/or cords showed a reduction of 92 nodules and/or cords. CONCLUSION: In 206 DD patients further disease progression was stopped in most patients. Radiotherapy proved to be well-tolerated, successful and satisfying for the patients.

[Intrathoracic Vacuum-Assisted Closure in the Treatment of Pleural Empyema and Lung Abscess]. / Intrathorakale Vakuumtherapie beim Pleuraempyem und Lungenabszess.

BACKGROUND: Complex pleural empyema or lung abscesses are either characterised by long-standing treatment (including treatment failure) or by a bad general condition of the patient (multiple morbidity, sepsis). The operative rectification is often associated with increased morbidity and mortality rates in these cases. Traditionally, the therapeutic tendency for such patients was towards primary creation of a thoracic window including open wound treatment, but this was always also associated with a long sickness and restrictions in the quality of life. The intrathoracic vacuum treatment (VAC) offers here entirely new options in the treatment of complicated pleural empyema and lung abscesses. METHOD: We present an illustration of our own clinical experience associated with a selective literature research via Medline (keywords: VAC, vacuum-assisted closure, thoracic empyema). RESULTS: After the initial successes of the extrathoracic application of the VAC treatment, the procedure was also analysed for its intrathoracic/pleural use to treat pleural empyema and lung abscesses with and without bronchus stump insufficiency. Initially, the use of the intrathoracic VAC treatment was carried out via a thoracic window (with rib resection), later we developed a minimally invasive procedure (Mini-VAC) while relieving the osseous thorax. An additional intrapleural rinsing with antiseptics (Mini-VAC-Instill) is very practical in cases of proven germ populations. The benefits of the Mini-Vac/Mini-VAC-Instill are: immediate secretion suction with quick local cleaning, rapid germ eradication with a small risk of a fresh population, improvement of the expansion behaviour of the lung as well as short treatment times with quick reclosure of the thorax. In addition to many retrospective examinations, there has so far only been one cohort study in which the classic thoracic window was compared with the VAC treatment. The duration of the stomatic situation as well as the long-term survival in the VAC group were better here than those in the non-VAC group. CONCLUSION: The intrathoracic VAC treatment (Mini-Vac/Mini-VAC-Instill) is an innovative procedure that promotes wound cleaning and wound healing in complicated pleural empyema and lung abscesses. Due to the benefits of this procedure, including the improvement of the patient's comfort and the quality of life, the procedure has seen a rapid and broad clinical acceptance.

[Cleaning and disinfection of surfaces in hospitals: Data on structure, process and result in the Frankfurt/Main Metropolitan Area]. / Flächenreinigung und -desinfektion im Krankenhaus - Struktur-, Prozess- und Ergebnisqualität : Ergebnisse der infektionshygienischen Überwachung in Frankfurt am Main, 2014.

INTRODUCTION: In addition to hand hygiene and reprocessing of medical products, cleaning and disinfection of surfaces is also an important issue in the prevention of germ transmission and by implication infections. Therefore, in 2014, the quality of the structure, process and result of surface preparation of all hospitals in Frankfurt am Main, Germany, was monitored. METHODS: All 17 hospitals transferred information on the quality of structure. Process quality was obtained through direct observation during cleaning and disinfection of rooms and their plumbing units. Result quality was gained using the fluorescent method, i.e. marking surfaces with a fluorescent liquid and testing if this mark has been sufficiently removed by cleaning. RESULTS: Structure quality: in all hospitals the employees were trained regularly. In 12 of them, the foremen had the required qualifications, in 6 hospitals unclarity as to the intersection of the cleaning and care services remained. In 14 hospitals only visible contamination was cleaned on the weekends, whereas complete cleaning was reported to take place in 12 hospitals on Saturdays and in 2 hospitals on Sundays. The contractually stipulated cleaning (observations specified in brackets) averaged 178 m(2)/h (148 m(2)/h) per patient room and 69 m(2)/h (33 m(2)/h) for bathrooms. Process quality: during process monitoring, various hand contact surfaces were prepared insufficiently. Result quality: 63 % of fluorescent markings were appropriately removed. CONCLUSION: The need for improvement is given especially in the area of the qualification of the foremen and a in a clear definition of the intersection between cleaning and care services, as well as in the regulations for weekends and public holidays.

[Para- and Postpneumonic Pleural Empyema: Current Treatment Strategies in Children and Adults]. / Para- und postpneumonisches Pleuraempyem: aktuelle Behandlungsstrategien bei Kindern und Erwachsenen.

INTRODUCTION: Parapneumonic pleural effusions arise from pneumonia and may develop into pleural empyema (PE). PE is defined as collection of pus in the pleural space with secondary inflammation of the visceral and parietal pleura. This review article describes the current treatment strategies for para- and postpneumonic PE both in children and adults. MATERIAL AND METHODS: Selective literature research via Medline (key words: pleural empyema, pleural empyema in children, thoracic empyema) and presentation of our own clinical experience with therapy recommendations. RESULTS: The incidence of postpneumonic PE is increasing in both children and adults. PE is associated with a high morbidity and mortality if it is not treated early and adequate. Progression of PE follows a characteristic morphological course, which is classified in three stages: the exsudative, fibrinopurulent, and organizing phase. Treatment should be adapted to these three phases including systemic antibiotic therapy and drainage of the pleural space. Intrapleural fibrinolysis can be performed with good success independent of age in the transition of stage 1 and 2. In persistent PE (stage 2), thoracoscopic decortication is recommended to avoid progression into the organizing phase (stage 3) with the need of an open decortication. In debilitated elderly patients the increasing use of intrathoracic vacuum therapy (Mini-VAC/Mini-VAC-instill) offers an effective and less invasive therapy option. CONCLUSION: Para- and postpneumonic PE requires an individualized and stage adapted therapy using a combination of medical and surgical treatment strategies with the aims of removing the source of infection and ensuring re-establishment of lung expansion.

[Hygiene in endoscopy in clinic and practice 2013 in comparison with 2003--structure and process quality]. / Struktur- und Prozessqualität bei der Aufbereitung flexibler Endoskope in Klinik und Praxis in Frankfurt am Main--2013 im Vergleich zu 2003.

BACKGROUND: Endoscopy is an important part of modern medical diagnostics and therapy. The invasive procedures are however associated with a risk to transmit infections. Against this background the KRINKO has published the "Hygienic requirements for the reprocessing of flexible endoscopes and endoscopic accessories" in 2002 and has updated these recommendations in 2012. In 2003 and 2013 all gastroenterological facilities in Frankfurt am Main using flexible endoscopes were monitored for compliance with the recommendations. METHODS: The inspections were performed after prior notice by a staff member of the health authority using a checklist which had been developed on the basis of the current KRINKO recommendations. RESULTS: In both years all institutions performing endoscopic procedures were visited: 2003 15 hospitals and 23 practices; 2013 14 clinics and 10 practices. In 2013 (data for 2003 in brackets) 100 % (93 %) of the hospitals and 60 % (22 %) of practices reprocessed their endoscopes by automated methods. The appropriate reprocessing and filling of water bottles for rinsing the scope channels with sterile water and the sterilisation of accessories were satisfactorily performed in 2003 and 2013 by all hospitals. However in 2013 only 90 % (2003: 74 %) of the practices correctly reprocessed water bottles and 80 % (52 %) used sterile water for filling the bottle. In 2013 100 % (2003: 57 %) of the practices correctly sterilised accessory instruments, while 2 practices used disposable, i. e., single-use materials. In 2013 all institutions performed microbiological tests according to KRINKO recommendations, while in 2003 all hospitals but only 43 % of the practices could present such tests. DISCUSSION: While the gastroenterological departments of Frankfurt hospitals already complied with the KRINKO recommendations in 2003, the inspection of several practices in 2003 had revealed considerable shortcomings in the implementation of these recommendations. Subsequently the practices have improved their hygiene management.

[Perioperative antibiotic therapy in thoracic surgery]. / Perioperative Antibiotikatherapie in der Thoraxchirurgie.

INTRODUCTION: In Germany no official guidelines exist for a specific perioperative antibiotic prophylaxis (PAP) in thoracic surgery. In this review, data regarding the PAP as well as antibiotic therapy of the postoperative pneumonia (POP) in thoracic surgery are described. METHODS: Selective literature researches were carried out in Medline with consideration of the official recommendations of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) as well as Paul-Ehrlich-Gesellschaft für Chemotherapie e. V. (PEG). RESULTS: The PAP is defined as a short and single application of an antibiotic agent preoperatively or during a surgical intervention. A PAP with first-generation or second-generation cephalosporins could significantly reduce the rate of surgical site infections after thoracic surgery. However, these few randomised trials could not demonstrate a distinct effect on the rate of POP and postoperative empyema. The incidence of POP is approximately 20-25 % after major thoracic surgery. Antibiotic therapy of POP should be performed early and be based on antibiotic sensitivity. CONCLUSION: Based on the few prospective, randomised studies a single dose of intravenous PAP with a cephalosporin is recommended in thoracic surgery. Therapy of the POP should include general procedures combined with a specific antibiotic therapy according to antibiotic sensitivity.

Intraoperative sRAGE kinetics. A new age-related outcome predictor of cardiac surgery.

BACKGROUND: Glycated proteins (advanced glycation endproducts, AGE) in tissue are associated with degenerative diseases. This study evaluated the role of sRAGE (soluble receptor for advanced glycation endproducts), a decoy receptor of AGEs in blood, for the outcome of patients after coronary artery bypass grafting (CABG). METHODS: A total of 90 patients undergoing CABG were analysed in two centres. Perioperative blood samples were collected before surgery up to 1 week postoperatively. sRAGE was measured by ELISA. Patients were subdivided regarding age (< 64 versus > 70 years, 14 % versus 35 % female), euroSCORE (< 3 versus > 4, 14 % versus 29 % female) and sRAGE changes between sternotomy and end of the operation (< 30 % versus > 45 %, 33 % versus 33 % female) and subsequently analysed with respect of postoperative outcome parameters. RESULTS: Preoperative sRAGE values did not correlate with the outcome of the patients. sRAGE levels increase within 10 min from 1,539 ± 96 to 5,311 ± 187 pg/ml after sternotomy, then returning to baseline levels within 2 days after surgery. Comparing the analysed possible risk factors age, euroSCORE and sRAGE changes, no difference was observed regarding 30-day mortality. Age and the euroSCORE are superior with respect of tachyarrythmia, whereas sRAGE kinetics seems to be superior with respect of prolonged postoperative respiration time/stay in the intensive care unit or catecholamine support. CONCLUSION: A prolonged, increased intraoperative sRAGE level is a new outcome predictor for patients undergoing CABG surgery, mutually complementary to the euroSCORE.

Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.

BACKGROUND: Assessing the pharmacokinetics of intrapleurally administered cisplatin during hyperthermic intrathoracic chemotherapy perfusion (HITHOC) following pleurectomy/decortication in patients with malignant pleural mesothelioma or advanced thymoma with pleural spread. METHODS: Pharmacokinetic analysis (ICP-MS) of intrapleural cisplatin with a dosage of 100 mg/m(2) (n = 5) or 150 mg/m(2) (n = 5) at 42°C perfusate temperature. Simultaneous pleural perfusion fluid and serum samples were collected at the beginning and every 15 min. Serum samples were collected at the end of the operation, 6, 12, and 24 hr postoperative. RESULTS: Mean cisplatin levels in the perfusate slightly decreased during the HITHOC. The mean area under the curve ratios (AUC perfusate :AUC serum ) of cisplatin were nearly similar. The mean AUCs of cisplatin in the perfusate were approximately 58 and 55 times greater than detected in the serum. The mean peak of cisplatin in the serum was reached after 1 hr of HITHOC. The AUC of cisplatin in the serum did not significantly differ (P = 0.18) between both groups up to 24 hr after perfusion. CONCLUSIONS: HITHOC with cisplatin provides a pharmacological advantage of high local intrapleural cisplatin concentrations. Elevation of the cisplatin dosage to 150 mg/m(2) did not lead to a significant increase of the systemic cisplatin concentration.

Novel instruments for in situ continuous Rn-222 measurement in groundwater and the application to river bank infiltration.

There is little known about the short-term dynamics of groundwater-surface water exchange in losing rivers. This is partly due to the paucity of chemical techniques that can autonomously collect high-frequency data in groundwater bores. Here we present two new instruments for continuous in situ (222)Rn measurement in bores for quantifying the surface water infiltration rate into an underlying or adjacent aquifer. These instruments are based on (222)Rn diffusion through silicone tube membranes, either wrapped around a pole (MonoRad) or strung between two hollow end pieces (OctoRad). They are combined with novel, robust, low-cost Geiger counter (222)Rn detectors which are ideal for long-term autonomous measurement. The down-hole instruments have a quantitative response time of about a day during low flow, but this decreases to <12 h during high-flow events. The setup was able to trace river water bank infiltration during moderate to high river flow during two field experiments. Mass-balance calculations using the (222)Rn data gave a maximum infiltration rate of 2 m d(-1). These instruments offer the first easily constructible system for continuous (222)Rn analysis in groundwater, and could be used to trace surface water infiltration in many environments including rivers, lakes, wetlands, and coastal settings.

[Radical pleurectomy and hyperthermic intrathoracic chemotherapy for treatment of thymoma with pleural spread]. / Radikale Pleurektomie und hypertherme intrathorakale Chemotherapie zur Behandlung pleural metastasierter Thymome.

INTRODUCTION: Patients with pleural thymoma spread (Masaoka stage IV a) should be treated within a multimodal treatment regime. However, the extent of local surgical resection to achieve optimal tumour control remains controversial. PATIENTS AND METHODS: Prospective analysis between September 2008 and April 2013 of all patients with a Masaoka stage IV a thymoma, who underwent radical pleurectomy/decortication (P/D) followed by hyperthermic intrathoracic chemotherapy (HITHOC). RESULTS: A total of 11 patients (male n = 7; mean age 46.5 ± 11.4 years) with a primary stage IV a thymoma (n = 3) or thymoma with pleural relapse (n = 8) were included after successful transsternal thymoma resection. WHO histological classification was: B1 n = 1, B2 n = 6, B3 n = 3 and C n = 1. A radical P/D (5/11; 45 %) was extended with resection of the pericardium and diaphragm in 6/11 (55 %) patients. After surgical resection (91 % complete macroscopic R0/R1-resection) the HITHOC with cisplatin (100 mg/m2 body surface area (BSA) n = 7; 150 mg/m2 BSA n = 4) was performed for one hour at 42 °C. Operative revision was necessary in two patients (chylo- and hematothorax) with one patient also requiring temporary renal replacement therapy due acute renal failure (cisplatin 150 mg/m2 BSA). 30-day mortality was 0 %. Local recurrence (pulmonary n = 1, paravertebral n = 2) was documented in 3/10 (30 %) patients after R0/R1 resection. After a mean follow-up of 23 months the overall median survival was 27 months and 82 % (9/11) patients are still alive at the end of the study period. CONCLUSIONS: Masaoka stage IV a thymoma could be safely treated with lung-sparing radical P/D and HITHOC with cisplatin in a multimodality treatment regime. Early results with respect to recurrence and survival are encouraging, but further studies are warranted and we have to await long-term results.

Methane in aquifers and alluvium overlying a coal seam gas region: Gas concentrations and isotopic differentiation.

The detection and attribution of methane in aquifers overlying oil and gas reservoirs has recently gained increasing attention internationally. The Surat Basin, in the Great Artesian Basin (GAB), Australia, hosts a coal seam gas (CSG) reservoir, with feedlots, town water supply, mines and agriculture that extract groundwater from aquifers that underly and overly the gas reservoir. This study aimed to use a multi-isotopic approach to differentiate biogenic methane generated in situ in GAB aquifers and the Condamine Alluvium, from the biogenic CSG produced from the underlying Walloon Coal Measures reservoir, to understand if gas had migrated or not. Dissolved methane (0.001 to 160 mg/l) and total methane concentrations (up to 91,818 ppmv) were measured using closed sampling methods and were higher than from open direct fill sampling (<0.001 to 25.4 mg/l), especially in gassy bores that contain dissolved methane above 10 to 13 mg/l. The CSG production waters and a gassy overlying aquifer bore had the most depleted water isotopes, and also the most enriched δ13C-DIC indicating strong methanogenesis. The majority of aquifers have isotopic signatures (δ13C-DIC, CH4 and CO2) indicating in situ methane production by primary CO2 reduction or fermentation, distinct from secondary microbial CO2 reduction in the CSG reservoir. Fractionation factors support methane production mainly via CO2 reduction, with fermentation in a subset of aquifer samples. The gas wetness parameters (636 to 20,000) are consistent with mainly microbial gases, with low dissolved ethane (max 0.04 mg/l). The majority of aquifer and alluvium samples in this study are consistent with in situ methane production, not migration, however in several gassy bores the methane source could not be clearly identified. This study is broadly applicable to understanding methane sources in aquifers overlying CSG reservoirs.

Improved dynamic response assessment for intra-articular injected iron oxide nanoparticles.

The emerging importance of nanoparticle technology, including iron oxide nanoparticles for monitoring development, progression, and treatment of inflammatory diseases such as arthritis, drives development of imaging techniques. Studies require an imaging protocol that is sensitive and quantifiable for the detection of iron oxide over a wide range of concentrations. Conventional signal loss measurements of iron oxide nanoparticle containing tissues saturate at medium concentrations and show a nonlinear/nonproportional intensity to concentration profile due to the competing effects of T1 and T2 relaxation. A concentration calibration phantom and an in vivo study of intra-articular injection in a rat knee of known concentrations of iron oxide were assessed using the difference-ultrashort echo time sequence giving a positive, quantifiable, unambiguous iron signal and monotonic, increasing concentration response over a wide concentration range in the phantom with limited susceptibility artifacts and high contrast in vivo to all other tissues. This improved dynamic response to concentration opens possibilities for quantification due to its linear nature at physiologically relevant concentrations.