Increasing chloride concentrations in Lake Constance: characterization of sources and estimation of loads

The chloride concentration in Lake Constance, by volume the second largest lake in Europe, has increased by a factor of 2.4 during the past 40years. Based on a chloride budget for the year 2006, we estimated total chloride imports to the catchment at 101ktyear−1. Road deicing salts contributed 52%, waste water 23%, farming 11%, soil weathering 9%, precipitation and solid waste incineration 3% to this import. River monitoring programs in Switzerland, Germany, and Austria in 2006 traced an average total chloride export from the catchment into Lake Constance of almost 70kt and an export from the lake of 56kt. About one-third of this load to the lake originated from the Alpine Rhine catchment (Switzerland), and about 60% from various smaller tributaries in Austria and Germany. The average annual import of chloride to Lake Constance for the years 1995-2007 was 60kt, the export almost 57kt. This budget is in good agreement with the observed increase in the chloride content of the lake and thus confirms the appropriateness and quality of the long-term monitoring program conducted by Swiss, German and Austrian laboratories. For the year 2006, we estimated that about 65% of the chloride spread onto roads for deicing and manure on cultivated land reached the lake within the year of their application. The missing 35% remained transiently in the soil and groundwater of the catchmen

Radiolysis of [1.1.1] propellane and of aziridines: fate of their molecular ions

Bei der Ionization von [1.1.1]Propellan (PRP+.) in Tieftemperaturmatrizen entsteht eine photolabile Spezies, die eine breite, schwache Bande im NIR Bereich (λmax = 1440 nm) und ein Triplett von 5.4 G eines Quintetts von 14.8 G im ESR Spektrum aufweist. Nach Bestrahlung mit NIR Licht wird diese Spezies in das Radikalkation von Vinylidencyclopropan (VCP+.) umgewandelt, welches unabhängig durch Ionisation von VCP nachgewiesen wurde. Quantenchemische Rechnungen zeigen, dass die spektroskopischen Eigenschaften des photolabilen Zwischenproduktes vergleichbar sind mit jenen des Radikalkations von Dimethylenallen (DIA+.). DIA+. wird auch bei der Ionisation von Dimethylencyclopropan (DMC) gebildet was darauf hinweist, dass DMC+. bei der Bildung von DIA+. aus PRP+. ein Intermediat darstellt. Die Potentialfläche, welche DIA+. und PRP+. verbindet, wurde untersucht und auf dem CCSD(T)/cc-pVDZ// B3LYP/6-31G* Niveau vollständig charakterisiert. Dabei wurde festgestellt, dass vibronische Wechselwirkungen beim Mechanismus des spontanen Zerfalls von ionisiertem PRP nach DIA+. eine wichtige Rolle spielen. Optische Spektren weisen auf die Bildung zusätzlicher Produkte bei Ionisation von PRP, DMC oder VCP in Freon- and Argonmatrizen hin; insbesondere jene von Vinylallen (VIA+.) , das ebenfalls durch Ionisation von VIA hergestellt und charakterisiert werden konnte. Experimente in Argonmatrizen zeigten ein weiteres Zwischenprodukt A, welches photochemisch zum Radikalkation von Cyclopentadien (CP+.) umgelagert werden konnte. A konnte nicht identifiziert werden, aber verschiedene Spezies, welche für die beobachteten Spektren verantwortlich sein könnten, wurden vorgeschlagen. Weiterführende Arbeiten werden nötig sein, um die unbekannten Intermediate, welche bei den erwähnten Umlagerungen auftreten, zu identifizieren. Der zweite Teil dieser Arbeit beschreibt die Bildung von Azomethinylid, Y, und des entsprechenden Radikalkations. Die experimentelle Untersuchung der Kraftkonstanten der C-N Bindungen in Y und der Vergleich mit jenen des Allylradikals sind von theoretischem Interessen. Durch das Hinzuziehen von Y-d1 und Y-d4 sollte es durch Skalierung des Kraftfeldes der drei Isotopomere möglich sein, diese Kraftkonstanten zu ermitteln. Weiter wird gezeigt, dass Substituenten - im besonderen Phenylgruppen - beim Verhalten der Aziridine unter Bedingungen von photoinduziertem Elektronentransfer (PET) eine wichtige Rolle spielen. N-Phenylringe stabilisieren das Aziridin-Radikalkation während C-Phenylringe bevorzugt das ringgeöffnete Azomethinylid Kation stabilisieren. Das Mass dieser Stabilisierung kann ermittelt werden indem der Energiebedarf für die Rotation der Phenylgruppe in eine senkrechte Position berechnet wird, in der die Resonanz zwischen der Phenylgruppe und dem Aziridinring bzw. dem Azomethinylid unterdrückt wird. Experimente und Berechnungen zeigten, dass das N-Phenylaziridin Radikalkation, NPA+, derart stark stabilisiert wird, dass es weder durch Ionisation noch durch anschliessende elektronische Anregung des Radikalkations zur Ringöffnung gebracht werden kann. Methylgruppen an den C-Atomen von NPA bewirken ein gewisses Absenken des Übergangszustandes der Ringöffnung, aber der Effekt ist zu gering, um die Überwindung der thermischen Barriere zu ermöglichen. Im Gegensatz dazu bewirkt C-Phenylsubstitution eine ausgeprägte Stabilisierung des Übergangszustandes der Ringöffnung relativ zum Edukt (und dem Produkt). Damit erleiden N-H- und N-Alkyl-C-Phenylaziridine unmittelbar nach Ionisierung Ringöffnung. Die Frage, welcher der beiden Effekte im Falle des C,N-Diphenylaziridins "gewinnt", konnte nicht befriedigend beantwortet werden. Jedoch genügte im Falle von ionisiertem Triphenylaziridin, TPA, eine kurze Photolyse, um eine Ringöffnung zu induzieren. Damit ist der Gebrauch von Aziridinen, die durch Ionisierung geöffnet werden, um mit A=B Dipolarophilen [3+2]Cycloadditionen einzugehen, auf jene Derivate beschränkt, bei denen die ring-geschlossene Form nicht zu stark von den Substituenten stabilisiert wird.On ionization of [1.1.1]propellane (PRP+.) in cryogenic matrices a photolabile species with a broad, weak NIR band (λmax = 1440 nm) and an ESR spectrum consisting of a 14.8 G quintet of 5.4 G triplets is formed. On NIR irradiation this species is converted into the radical cation of vinylidenecyclopropane (VCP+.), which was generated independently by ionization of VCP. Quantum chemical calculations show that the spectroscopic features of the photolabile intermediate are compatible with its assignment to the radical cation of dimethylene allene (DIA+.). DIA+. is also formed on ionization of dimethylenecyclopropane (DMC) which suggests that DMC+. is an intermediate in the formation of DIA+. from PRP+. The potential energy surface connecting DIA+. and PRP+. is explored and fully characterized at the CCSD(T)/cc-pVDZ//B3LYP/6- 31G* level. Thereby it is found that vibronic interactions play an important role in determining the mechanism for the spontaneous decay of ionized PRP to DIA+. Optical spectra indicate the formation of additional products on ionization of PRP, DMC, or VCP in Freon and Argon matrices, notably the radical cation of vinylallene (VIA+.) , which was also generated independently by ionization of VIA. Argon matrix experiments reveal also the presence of an intermediate A+. which can be transformed photochemically into the radical cation of cyclopentadiene (CP+). Intermediate A could not be identified, but several species which could be responsible for the corresponding spectroscopic manifestations are proposed. Further work will also be needed to shed more light on some other species which were observed during the above transformations. The second part of this work describes the generation of azomethine ylid, Y, and its radical cation. It is of theoretical interest to investigate experimentally the force constants for the symmetric and asymmetric stretching deformation of the C-N bonds of Y and to compare them to those of the allyl radical. By investigating also Y-d1 and the Y-d4 it should be possible to determine these force constants by fitting the force field of the three isotopomers. Furthermore we showed that substituents - particularly phenyl groups - play a very important role in determining the behavior of aziridines under photoinduced electron transfer (PET) conditions. N-phenyl rings stabilize the aziridine radical cation, whereas C-phenyl rings stabilize preferentially the ring-opened azomethine ylid cation. The extent of this stabilization can be assessed by calculating the energy increase on rotating the phenyl ring to a perpendicular position, so that resonance between the phenyl and the aziridine or the azomethine ylid moieties, respectively, is suppressed. Experiments and calculations showed that N-phenylaziridine radical cation, NPA+, is so strongly stabilized that it cannot undergo ring-opening on ionization (nor on subsequent electronic excitation of the radical cation). Methyl groups on the C atoms of NPA cause some lowering of the ring-opening transition state but the effect is too weak to allow a thermal crossing of the barrier. In contrast, C-phenyl substitution leads to a pronounced stabilization of the ring-opening TS, whereas the stabilization of the reactant and of the product are quite similar. Therefore N-H and N-alkyl-C-phenylaziridines undergo immediate ring-opening on ionization. The question which effect "wins" in ionized C,Ndiphenyl aziridine could not be answered satisfactorily. However for triphenylaziridine, TPA, short photolysis suffices to induce ring-opening. Thus, the use of aziridines, opened by ionization to perform [3+2]cycloadditions with dipolarophiles A=B, is limited to derivatives where substituents do not stabilize the ring-closed form too much

Procalcitonin and pneumonia: Is it a useful marker?

An ideal biomarker for pneumonia should allow an early diagnosis and differential diagnosis from noninfectious conditions and should inform about the course and prognosis of the disease. Procalcitonin (PCT) covers these features better as compared to more commonly used biomarkers like C-reactive protein or leukocyte count. PCT complements and improves the assessment of pneumonia based on careful patient history, dedicated physical examination, and appropriate cultures. Importantly, a PCT-based therapeutic strategy can safely and markedly reduce antibiotic courses in community-acquired pneumonia. However, as is the cast with all diagnostic surrogate markers, PCT can be increased in noninfectious conditions and may remain low in bacterial infections, especially localized infections. This stresses the importance of follow-up measurements, because PCT levels in these patients often show a gradual increase during follow-up. Although PCT is better than more common biomarkers for the prognosis of pneumonia and to predict survival and outcome, novel biomarkers show an even better prognostic accurac

When once is not enough – further evidence of procalcitonin-guided antibiotic stewardship

Every day, critical care physicians around the world face the same challenge of the optimal timing of antimicrobial administration: when to start and when to stop antibiotics. Duration of antibiotic therapy for sepsis is mostly based on expert opinion, but its reduction is arguably the most promising approach to decrease emergence and selection of antibiotic resistance. The study by Hochreiter and colleagues presents another piece of evidence suggesting that procalcitonin may indeed be a valuable diagnostic parameter to guide antibiotic treatment duration, despite the ongoing controversy about the diagnostic accuracy of pro-calcitonin

Copeptin: a new and promising diagnostic and prognostic marker

The study conducted by Seligman and coworkers included in the previous issue of Critical Care demonstrates that copeptin is a promising marker to predict outcome in patients with ventilator-associated pneumonia. In recent years, copeptin has emerged as a new prognostic marker in a variety of diseases, such as sepsis, community-acquired pneumonia, chronic obstructive pulmonary failure, heart failure and myocardial infarction. What is the pathophysiological basis for these findings? Copeptin together with vasopressin is co-secreted from the posterior pituitary and therefore mirrors the amount of vasopressin in the circulation. Vaso-pressin is a main secretagogue of the hypothalamo–pituitary–adrenal axis, thereby mirroring the individual stress level. Furthermore, vasopressin is an important hormone in salt and volume regulation. In this context, copeptin is also a diagnostic marker in patients with diabetes insipidus and in patients with disordered water states

Outcome of radioiodine therapy without, on or 3days off carbimazole: a prospective interventional three-group comparison

Purpose: Carbimazole ameliorates hyperthyroidism but reduces radioiodine uptake and adversely affects the outcome of simultaneous radioiodine therapy. We explored whether withdrawal of carbimazole for 3 days can restore the outcome of radioiodine treatment without concurrent exacerbation of hyperthyroidism. By generating three groups with comparable radioiodine uptake, we also investigated whether the effect of carbimazole depends on the radioiodine uptake. Methods: Stratified by a radioiodine uptake >30%, 227 consecutive adult patients were prospectively assigned to radioiodine therapy (target dose 200Gy) without, on or 3days off carbimazole. Patients were clinically (Crooks-Wayne score) and biochemically (T3, fT4, TSH) followed up after 3, 6 and 12months. Primary endpoint was outcome 12months after radioiodine therapy. Results: A total of 207 patients completed follow-up (toxic nodular goitre, n=117; Graves' disease, n=90). The overall success rate was 71.5%. Patients without and 3days off carbimazole had similar biochemical (81.4% and 83.3%, respectively; p=0.82) and clinical outcomes [median (range) Crooks-Wayne score 0 (0-16) and 1 (0-10), respectively; p=0.73], which were both higher than in patients on carbimazole [42.6%, p<0.001; Crooks-Wayne score 3 (0-30), p<0.03]. Time to achieve cure was delayed on carbimazole. No changes in thyroid hormone levels occurred after 3days' discontinuation of carbimazole. Logistic regression revealed that all observed cure rates were independent of entity, sex, age, thyroid volume, radioiodine uptake, radioiodine half-life, fT4, T3 and TSH. Conclusion: Patients under carbimazole treatment can be referred for radioiodine therapy after withdrawal of carbimazole for only 3days. Three days of carbimazole withdrawal is long enough to restore the success of radioiodine therapy and short enough to avoid the risk of exacerbation of hyperthyroidis

Severe Hyperkalemia and Bilateral Adrenal Metastasis

Adrenal metastases are a common finding in metastatic lung and breast cancer. Often there are no clinical symptoms suggesting them. In this paper, we present a case of a 66-year-old man with metastatic lung cancer suffering from severe hyperkaliemia due to hypoaldosteronism as a result of bilateral adrenal metastasis

Impact of bisphosphonate wash-out prior to teriparatide therapy in clinical practice

Concurrent use of bisphosphonate therapy reduces the anabolic effect of teriparatide. Consequently, in clinical practice bisphosphonates are discontinued and teriparatide therapy held for a few months to allow bone turnover to increase. We aimed to evaluate the effect of prior bisphosphonate exposure and the effect of bisphosphonate wash-out on the treatment response to teriparatide. Thirty-nine patients with primary osteoporosis (mean age 63.6±14.0years), including 26 patients previously treated with oral bisphosphonates (median duration 53months) and 13 bisphosphonate-naïve patients were started on teriparatide (20μg daily) and followed prospectively over 12months. The primary study outcome was change in bone formation markers (PINP, bone ALP, osteocalcin). Secondary outcomes included changes in bone resorption (βCTX) and 12-month changes in BMD. Markers of bone formation increased early during teriparatide therapy and were followed by an increase in βCTX (p<0.001). The magnitude of the increase in bone markers was comparable in both patient groups irrespective of prior bisphosphonate exposure; similarly, increases in BMD after 12months were not significantly different between bisphosphonate-pretreated and bisphosphonate-naïve patients (lumbar spine 7.1 vs. 8.9%, p=0.58; total hip 4.1 vs. 1.1%, p=0.48). The response of teriparatide was not related to the duration of bisphosphonate wash-out (median duration 4.2months). This study confirms that beneficial effects of teriparatide on intermediate bone endpoints can be translated into clinical practice with less constringent methodological circumstances than in RCTs. Furthermore, as bisphosphonate wash-out does not appear to influence the treatment effect, teriparatide therapy can be started immediately after ceasing bisphosphonate therapy and wash-ou

Procalcitonin: Importance for the diagnosis of bacterial infections

In contrast to calcitonin which is primarily synthesized in the thyroid, procalcitonin is a prohormone which is synthesized in many different tissues of infected organs. To diagnose mild, localized, or early infections an assay needs to have a functional assay sensivity of approximately 0.02μg/L. We demonstrated that procalcitonin modifies the outcome of respiratory infections with regard to minimizing the use of antibiotics and duration of antibiotic treatment. High concentrations, especially over time, indicate high risk of a severe outcome. In this respect, procalcitonin is superior to other infection markers, such as C-reactive protein. High procalcitonin levels can also be found in non-bacterial diseases, such as malaria, severe trauma, burns, and medullar carcinoma of the thyroid. Procalcitonin, as a marker, has improved the diagnosis of bacterial infections. However, procalcitonin needs to be used in conjunction with other laboratory markers, clinical examination, and medical histor