A guideline to frame stressor effects in freshwater ecosystems.

Environmental policies fall short in protecting freshwater ecosystems, which are heavily threatened by human pressures and their associated stressors. One reason is that stressor effects depend on the context in which they occur and it is difficult to extrapolate patterns to predict the effect of stressors without these being contextualized in a general frame. This study aims at improving existing decision-making frameworks such as the DPSIR approach (Driver-Pressure-State-Impact-Response) or ERA (Environmental Risk Assessment) in the context of stressors. Here, we delve into stressor-impact relationships in freshwater ecosystems and develop a guideline which includes key characteristics such as stressor type, stressor duration, location, the natural levels of environmental variables to which each ecosystem is used to, among others. This guideline is intended to be useful in a wide range of ecosystem conditions and stressors. Incorporating these guidelines may favor the comparability of scientific results and may lead to a substantial advancement in the efficacy of diagnosis and predictive approaches of impacts.

Multiple stressor effects on benthic macroinvertebrates in very large European rivers - A typology-based evaluation of faunal responses as a basis for future bioassessment.

Two factors complicate the ecological status classification of very large rivers in Europe according to the EU Water Framework Directive: First, current assessment methods do not fully consider the specific ecology of very large rivers (such as lateral connectivity and the role of floodplains for ecological status). Second, most of Europe's very large rivers have been severely altered by human activities such as flood protection, damming and navigation. The aim of our study is to develop an assessment method for very large rivers by identifying suitable biological metrics as the basis for multi-metric bioassessment using benthic invertebrates. Based on the pan-European typology of very large rivers by Borgwardt et al. (2019), we established a river type-specific assessment approach using invertebrate samples from 25 European countries and 94 very large rivers. The frequency and intensity of eight pressures jointly acting on the sampling sites were described, and a selection of suitable invertebrate community metrics were correlated with the pressure intensities to establish pressure-response relationships. The very large river types differ in terms of relevant pressures and pressure combinations, with the invertebrate communities distinctly responding to these pressure patterns. Neozoa dominance correlated strongly with 'navigation', being a major pressure at very large rivers, which entails severe hydro-morphological alterations such as channelization, riparian vegetation alteration and impoundment. Under combined pressures, a critical community turnover became evident in terms of neozoa outnumbering EPT taxa and the ratio of hemilimnic invertebrates decreasing. We propose ten bioassessment metrics, including measures of biological diversity as well as newly generated indicators, for the development of a European type-specific assessment method for very large rivers.

Catchment properties and the photosynthetic trait composition of freshwater plant communities.

Unlike in land plants, photosynthesis in many aquatic plants relies on bicarbonate in addition to carbon dioxide (CO2) to compensate for the low diffusivity and potential depletion of CO2 in water. Concentrations of bicarbonate and CO2 vary greatly with catchment geology. In this study, we investigate whether there is a link between these concentrations and the frequency of freshwater plants possessing the bicarbonate use trait. We show, globally, that the frequency of plant species with this trait increases with bicarbonate concentration. Regionally, however, the frequency of bicarbonate use is reduced at sites where the CO2 concentration is substantially above the air equilibrium, consistent with this trait being an adaptation to carbon limitation. Future anthropogenic changes of bicarbonate and CO2 concentrations may alter the species compositions of freshwater plant communities.

Bernese periacetabular osteotomy through a double approach : Simplification of a surgical technique.

OBJECTIVE: Reorientation of the acetabulum to normalize load transfer or avert femoroacetabular pincer impingement to prevent osteoarthritis of the hip. INDICATIONS: Persisting acetabular dysplasia after closure of growth plates or acetabular malrotation. CONTRAINDICATIONS: High dislocation of hip, secondary acetabulum, increased misalignment on functional X­ray, high-grade mobility restriction. Relative: degenerative changes, advanced age. SURGICAL TECHNIQUE: Bernese periacetabular osteotomy through two incisions; all bone cuts are carried out under direct vision. The osteotomies are equivalent to the classic Ganz method. In a slightly tilted forward lateral decubitus position, a posterior incision is applied for the ischium osteotomy and the caudal portion of the retroacetabular osteotomy. The pubis and ilium osteotomies are performed in a supine position through an anterior approach with subsequent reorientation and screw fixation. The rectus femoris is not dissected unless joint exposure is required. POSTOPERATIVE MANAGEMENT: Partial weight bearing with 20 kg for the first 6 weeks postoperatively, followed by stepwise transition to full loads after radiological control. RESULTS: In total, 34 patients (37 hips) were followed up for 20.4 ± 10.3 months. Tönnis osteoarthritis scale levels remained constant. The center-edge angle of Wiberg increased from 13.2 ± 7.5° to 26.5 ± 6.7°, the Tönnis angle (acetabular index) changed from 13.8 ± 6.5° to 3.4 ± 4.4°. At follow-up, the Merle d'Aubigné and Postel score was 16.5 ± 1.4; the modified Harris hip score 87.6 ± 13.9 and the International hip outcome tool (iHOT)-12 78.2 ± 20.3 points. The mean surgical time was 213 ± 29 min. Severe complications were not observed.

Pentraxin-3 level at admission is a strong predictor of short-term mortality in a community-based hospital setting.

BACKGROUND: The pattern recognition molecule pentraxin-3 (PTX3) is a novel potential marker of prognosis, as elevated levels are associated with both disease severity and mortality in patients with a wide range of conditions. However, the usefulness of PTX3 as a prognostic biomarker in a general hospital setting is unknown. PATIENTS AND METHODS: The study cohort consisted of 1326 unselected, consecutive patients (age >40 years) admitted to a community hospital in Copenhagen, Denmark. Patients were followed until death or for a median of 11.5 years after admission. The main outcome measure was all-cause mortality. Serum samples collected from patients at admission and from 192 healthy control subjects were quantified for PTX3 level by enzyme-linked immunosorbent assay. RESULTS: PTX3 was elevated in patients (median 3.7 ng mL(-1) , range 0.5-209.8) compared with healthy nonhospitalized subjects (median 3.5 ng mL(-1) , range 0.0-8.3; P = 0.0003). Elevated PTX3 levels, defined as above the 95th percentile of the concentration in healthy subjects, were associated with increased overall mortality during the study (P < 0.0001). This increase in mortality was greatest in the short term, with an unadjusted hazard ratio (HR) of 6.4 [95% confidence interval (CI) 3.8-11.0] at 28 days after admission, compared to 1.7 (95% CI 1.4-2.0) at the end of follow-up. These results were still significant after adjustment for age, gender and glomerular filtration rate: adjusted HR of 5.0 (95% CI 2.9-8.8) and 1.4 (95% CI 1.2-1.8), respectively. CONCLUSION: These results suggest that PTX3 could be a widely applicable marker of short-term mortality in hospitalized patients and may be useful in the initial risk stratification.

Single event time series analysis in a binary karst catchment evaluated using a groundwater model (Lurbach system, Austria).

The Lurbach karst system (Styria, Austria) is drained by two major springs and replenished by both autogenic recharge from the karst massif itself and a sinking stream that originates in low permeable schists (allogenic recharge). Detailed data from two events recorded during a tracer experiment in 2008 demonstrate that an overflow from one of the sub-catchments to the other is activated if the discharge of the main spring exceeds a certain threshold. Time series analysis (autocorrelation and cross-correlation) was applied to examine to what extent the various available methods support the identification of the transient inter-catchment flow observed in this binary karst system. As inter-catchment flow is found to be intermittent, the evaluation was focused on single events. In order to support the interpretation of the results from the time series analysis a simplified groundwater flow model was built using MODFLOW. The groundwater model is based on the current conceptual understanding of the karst system and represents a synthetic karst aquifer for which the same methods were applied. Using the wetting capability package of MODFLOW, the model simulated an overflow similar to what has been observed during the tracer experiment. Various intensities of allogenic recharge were employed to generate synthetic discharge data for the time series analysis. In addition, geometric and hydraulic properties of the karst system were varied in several model scenarios. This approach helps to identify effects of allogenic recharge and aquifer properties in the results from the time series analysis. Comparing the results from the time series analysis of the observed data with those of the synthetic data a good agreement was found. For instance, the cross-correlograms show similar patterns with respect to time lags and maximum cross-correlation coefficients if appropriate hydraulic parameters are assigned to the groundwater model. The comparable behaviors of the real and the synthetic system allow to deduce that similar aquifer properties are relevant in both systems. In particular, the heterogeneity of aquifer parameters appears to be a controlling factor. Moreover, the location of the overflow connecting the sub-catchments of the two springs is found to be of primary importance, regarding the occurrence of inter-catchment flow. This further supports our current understanding of an overflow zone located in the upper part of the Lurbach karst aquifer. Thus, time series analysis of single events can potentially be used to characterize transient inter-catchment flow behavior of karst systems.

Intercalibrating classifications of ecological status: Europe's quest for common management objectives for aquatic ecosystems.

Halting and reversing the deterioration of aquatic ecosystems requires concerted action across state boundaries and administrative barriers. However, the achievement of common management objectives is jeopardised by different national quality targets and ambitions. The European Water Framework Directive requires that quality classifications are harmonised via an intercalibration exercise, ensuring a consistent level of ambition in the protection and restoration of surface water bodies across the Member States of the European Union. We outline the key principles of the intercalibration methodology, review the achievements of intercalibration and discuss its benefits and drawbacks. Less than half of the required intercalibration has been completed, mostly due to a lack of national assessment methods. The process has fostered a scientific debate on ecological classification with important implications for environmental management. Despite a significant level of statistical abstraction, intercalibration yielded a fundamental and unified vision of what constitutes good ecology across Europe, in principle ensuring greater parity in the funds invested to achieve good ecological status.

[Dislocation of voice prostheses. Interdisciplinary management of diagnostics and treatment]. / Dislokation von Stimmprothesen. Interdisziplinäres Vorgehen bei Diagnostik und Therapie.

Tracheoesophageal voice prostheses after total laryngectomy are infrequently the cause of severe complications. We report on a patient with threefold dislocation of a Provox prosthesis, each with suspected oesophageal loss. The patient came to our hospital with acute dyspnoea. An urgent bronchoscopy showed two prostheses in the right and one in the left main bronchus, which had caused inflammation with extensive occlusion of the bronchus. All three prostheses could be recovered.

Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders.

Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine. However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 microg kg(-1) min(-1)) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by (133)Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial Doppler and the diameter of peripheral arteries by transdermal ultrasound (C-scan). ADM did not induce significantly more headache or migraine compared with placebo (P = 0.58). CBF was unaffected by ADM infusion (global CBF, P = 0.32 and rCBF(MCA), P = 0.38) and the same applied for the V(MCA) (P = 0.18). The superficial temporal artery dilated compared with placebo (P < 0.001), and facial flushing was seen after ADM administration (P = 0.001). In conclusion, intravenous ADM is not a mediator of migraine headache and does not dilate intracranial arteries.

The headache-inducing effect of cilostazol in human volunteers.

We have previously shown that nitric oxide (NO) and cyclic guanosine monophosphate (GMP) may cause headache and migraine. However, not all findings in previous studies can be explained by an activation of the NO-cGMP pathway. Calcitonin gene-related peptide (CGRP) causes headache and migraine in migraine patients, but CGRP receptor activation causes an increase in cyclic adenosine monophosphate (cAMP). In order to investigate the role of cAMP in vascular headache pathogenesis, we studied the effect of cilostazol, an inhibitor of cAMP degradation, in our human experimental headache model. Twelve healthy volunteers were included in a double-blind, randomized, crossover study. Placebo or cilostazol (200 mg p.o.) was administered on two separate study days. Headache was scored on a verbal rating scale (0-10) and mechanical pain thresholds were measured with von Frey hairs. The median peak headache score 0-16 h postdose was 0 (range 0-2) after placebo and 3.5 (range 0-7) after cilostazol (P = 0.003). The median headache curve peaked at 6-9 h postdose. The headaches induced were usually bilateral and pulsating. Nausea occurred in two volunteers, photo- and phonophobia were not seen. Two volunteers had a headache that fulfilled International Headache Society criteria for migraine without aura after cilostazol. No change in mechanical pain thresholds in the forehead was seen (P = 0.25). The headache after cilostazol was equal to or more severe than headache induced by glyceryl trinitrate in previous experiments. The present study thus indicates that increased levels of cAMP may play a role in headache and migraine pathogenesis.

Vasoactive intestinal polypeptide evokes only a minimal headache in healthy volunteers.

The role of the parasympathetic nervous system in the pathogenesis of migraine is disputed. The headache-eliciting effect of the parasympathetic neurotransmitter, vasoactive intestinal polypeptide (VIP), and its effect on cerebral arteries and brain haemodynamics has not been systematically studied in man. We hypothesized that infusion of VIP might induce headache in healthy subjects and cause changes in cerebral haemodynamics. VIP (8 pmol/kg per min) or placebo (0.9% saline) was infused for 25 min into 12 healthy young volunteers in a crossover, double-blind design. Headache was scored on a verbal rating scale from 0 to 10, regional cerebral blood flow (rCBF) was measured with single-photon emission computed tomography and (133)Xe inhalation and mean flow velocity in the middle cerebral artery (V(meanMCA)) was measured with transcranial Doppler ultrasonography. The headache was very mild with a maximum score of 2 and described as a pressing or throbbing sensation. Five participants developed headache during VIP and one during placebo. During the infusion, a significant drop in V(meanMCA) was seen for VIP compared with placebo (P < 0.001), but the effect quickly waned and no difference was found when comparing the time between 30 and 120 min. In addition, no significant difference in the diameter of the MCA could be found during the infusion. No significant differences in rCBF (P = 0.10) were found between VIP and placebo. A marked dilation of the superficial temporal artery was seen (P = 0.04) after VIP in the first 30 min but no difference was found when comparing the time between 30 and 120 min. We found no difference in mean arterial blood pressure between VIP and placebo days but the heart rate increased significantly on a VIP day compared with a placebo day (AUC(0-30 min), P < 0.001). Plasma VIP was significantly higher on a VIP day compared with placebo (AUC(0-80 min), P < 0.001). These results show that VIP causes a decrease in V(meanMCA) without affecting rCBF. In spite of a marked vasodilator effect in the extracranial vessels and increased plasma VIP, healthy subjects developed only a very mild headache.

The effect of circulating adenosine on cerebral haemodynamics and headache generation in healthy subjects.

Adenosine is an endogenous neurotransmitter that is released from the brain during hypoxia and relaxes isolated human cerebral arteries. Many cerebral artery dilators cause migraine attacks. However, the effect of intravenous adenosine on headache and cerebral artery diameter has not previously been investigated in man and reports regarding the effect of intravenous adenosine on cerebral blood flow are conflicting. Twelve healthy participants received adenosine 80, 120 microg kg(-1) min(-1) and placebo intravenously for 20 min, in a double-blind, three-way, crossover, randomized design. Headache was rated on a verbal scale (0-10). Regional cerebral blood flow (rCBF) with 133Xe inhalation and single-photon emission computed tomography (SPECT) and MCA flow velocity (V(MCA)) with transcranial Doppler, were measured in direct sequence. Six participants developed headache during 80 microg kg(-1) min(-1) and six during 120 microg kg(-1) min(-1) compared with none on placebo (P = 0.006). The headache was very mild and predominantly described as a pressing sensation. When correcting data for adenosine-induced hyperventilation, no significant changes in rCBF (P = 0.22) or V(MCA) (P = 0.16) were found between treatments. A significant dilation of the superficial temporal artery (STA) was seen (P < 0.001). These results show that circulating adenosine has no effect on rCBF or V(MCA), while it dilates the STA and causes very mild headache.

The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers.

BIBN4096BS is a CGRP-antagonist effective in the treatment of migraine. Blocking the receptor of a strong vasodilator involves a theoretical risk of causing cerebral vasoconstriction, a probability not previously investigated with BIBN4096BS. Seven healthy volunteers completed this double-blinded placebo-controlled crossover study. The volunteers received randomly 10 min infusions of either placebo, 2.5 mg or 10 mg of BIBN4096BS on 3 separate days. Transcranial Doppler was used to measure the middle cerebral artery blood flow velocity (V(MCA)); global and regional cerebral blood flow (rCBF(MCA)) was measured by 133-Xenon inhalation SPECT. The diameter of the temporal and radial artery was measured by high-resolution ultrasound. Systemic haemodynamics and partial pressure of CO(2) (P(et)CO(2)), and adverse events were monitored regularly. BIBN4096BS had no influence on global or regional cerebral blood flow, or on the blood flow velocity in the middle cerebral artery. There was no effect on systemic haemodynamics and adverse events were minor. We conclude that there is no effect of CGRP-receptor blockade on the cerebral or systemic circulation in humans. Circulating CGRP is therefore not likely to exert a vasodilatory activity in the resting state and the use of BIBN4096BS for acute migraine seems to be without risk of cerebral vasoactivity. These data suggest that BIBN4096BS is the first specific antimigraine drug without vasoactive effect.

Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache.

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP) degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12 migraine patients and in healthy subjects it induced significantly more headache than placebo. The aim of the present study was to determine whether the pain-inducing effects of sildenafil would be reflected in plasma levels of important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate (cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four women, six men) and 12 patients (12 women) suffering from migraine without aura were included in two separate double-blind, placebo-controlled, cross-over studies in which placebo or sildenafil 100 mg was administered orally. Plasma levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein. Despite the ability of sildenafil to induce headache and migraine, no significant differences in plasma levels of CGRP, cGMP and cAMP were detected after sildenafil compared with placebo. In conclusion, plasma levels of CGRP, cGMP and cAMP remain normal during sildenafil-induced headache or migraine. However, since previous studies indicate an important role of these signalling molecules, the present study questions whether cAMP and cGMP in peripheral blood can be used for monitoring pathophysiological events in headache and migraine mechanisms.

[The therapeutic results and early and late toxicities of the treatment of anal canal carcinoma by radiotherapy or chemoradiotherapy]. / Therapieergebnisse, Früh- und Spättoxizität der Behandlung des Analkanalkarzinoms durch Strahlentherapie oder Chemoradiotherapie.

From 1975 to 1989 114 patients with anal canal carcinoma were treated, 81 of these with radiotherapy (RT) alone and 33 with chemoradiotherapy (CRT), 80% respectively 82% of the patients were colostomy-free at the onset of therapy. RT was given to a total dose of 60 Gy in six weeks, for CRT additional simultaneous 5-fluorouracil (500 mg/m2 days 1 to 5 and 8 to 12) and mitomycin C (5 mg/m2 days 5 and 12) was administered. 67% respectively 82% of the patients had UICC stage II to IIIB disease predominantly with G2 and G3 squamous cell carcinomas. Local control after three years was 79% for the RT group vs. 82% for the CRT group. Three-year survival rate was 68% and 71%, respectively. These differences were not significant. Only for G1- compared to G3-tumors there is a significantly higher survival rate. Acute and late damage was slightly lower for the RT treatment group (77% and 25%) compared to the CRT group (79% and 30%). In both treatment groups there was one patient needing a permanent colostomy due to radiation induced proctitis. In conclusion, RT or CRT should be the primary form of treatment in patients with and canal carcinoma and abdominoperineal resection should only be performed in case of local recurrence or tumor persistence. The final decision about the indications for RT or CRT can only be made with the results of a prospective randomized trial.

The effects of two years of mestranol treatment on carbohydrate metabolism.

Twenty-nine menstrual age women who had a hysterectomy and oophorectomy were treated cyclically with 80 micrograms of mestranol per day for 2 yr. Their carbohydrate metabolism was evaluated prospectively by doing a 3 hr oral glucose tolerance test after a 100 g glucose load and measuring both blood glucose and plasma insulin levels. The tests were performed before drug treatment and after 2 yr of drug use. Those women that had a "normal" predrug test had some carbohydrate metabolism changes at the 2 yr test with significant elevations of the fasting, 1 and 2 hr blood glucose values, and also significant elevations of the 2 and 3 hr plasma insulin values. Those women with a "borderline abnormal" predrug test had no significant change in either parameter of carbohydrate metabolism however a trend toward similar changes was noted.

PIP: 29 menstrual age women who had hysterectomy and oophorectomy were treated cyclically with 80 mcg of mestranol/day for 2 years. Their carbohydrate metabolism was evaluated prospectively by doing a 3 hour oral glucose tolerance test after a 100 g glucose load and measuring both blood glucose and plasma insulin levels. Tests were performed before a drug treatment and after 2 years of drug usage. Those women who had normal predrug tests had some carbohydrate metabolism changes at the 2 year test with significant elevations of the fasting, 1, and 2 hour blood glucose values, and also significant elevations of the 2 and 3 hour plasma insulin values. Those women with a borderline abnormal predrug test had no significant change in either parameter of carbohydrate metabolism; however, a trend toward similar changes was noted.

Gonadotropin responses to graded GNRF injections in women with prior twin pregnancies.

Fifteen women with prior twin pregnancies and 20 women with prior singleton pregnancies were investigated in the luteal phase of their menstrual cycles. Measurements were made of their basal LH, FSH, estradiol, progesterone, testosterone and dihydrotestosterone levels as well as their LH and FSH responses to serial graded (0.5 microgram, 5.0 micrograms and 50.0 micrograms) intravenous injections of gonadotropin-releasing factor. The women with prior twin pregnancies were heavier and had a higher parity. Their basal serum progesterone and testosterone levels were not different, but they had lower basal serum estradiol levels and higher basal serum dihydrotestosterone levels. No differences were noted between either the basal or the stimulated gonadotropin (LH and FSH) levels. Thus, no identifiable pituitary trophic factors associated with or causing twinning could be identified in the population studied.

Carbohydrate metabolism studies in women using Brevicon, a low-estrogen type of oral contraceptive, for one year.

A prospective study of carbohydrate metabolism was done in 12 normal women over 1 year's time while they were using the low-estrogen type of oral contraceptive Brevicon, which contains 0.035 mg of ethinyl estradiol and 0.5 mg of norethindrone. The women had a 3-hour oral glucose tolerance test before starting the drug and then in 12 months, both blood glucose and plasma insulin levels were measured. After 1 year, there was no significant change in weight, blood pressure, or plasma insulin levels. There was a slight decrease in the fasting blood glucose value after 1 year's use (67.5 +/- 1.5 versus 63.2 +/- 1.3 mg/dl). The other glucose values were unchanged. The importance of these data in terms of mechanisms of action of the steroids on metabolism and the safety of oral contraceptive usage is discussed.