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Background: Basic knowledge of detailed spatiotemporal migration patterns is lacking for most migratory bird species. Using the smallest available geolocator, we aim to map autumn migration and wintering areas of north European wood warblers Phylloscopus sibilatrix and compare the spatiotemporal pattern with recoveries of individuals ringed across Europe. Results: A tracked wood warbler migrated south-south-east to sub-Saharan Africa in Sudan and then west-south-west to winter in Côte d'Ivoire. The timing and route fits well within the distribution of ring recoveries although the westward movement after the Sahara crossing is not revealed by the ring recoveries, but only few recoveries south of Sahara exist. Conclusions: The surprising westward movement south of the Sahara supplements the overall pattern revealed by ring recoveries and aids our understanding of the connectivity and site dependence in this generally declining species.

Protandry, the earlier arrival of males at the breeding grounds relative to females, is common in migratory birds. However, due to difficulties in following individual birds on migration, we still lack knowledge about the spatiotemporal origin of protandry during the annual cycle, impeding our understanding of the proximate drivers of this phenomenon. Here, we use full annual cycle tracking data of red-backed shrikes Lanius collurio to investigate the occurrence of sex-related differences in migratory pattern, which could be viewed as precursors (proximate causes) to protandry. We find protandry with males arriving an estimated 8.3 days (SE = 4.1) earlier at the breeding area than females. Furthermore, we find that, averaged across all departure and arrival events throughout the annual cycle, males migrate an estimated 5.3 days earlier than females during spring compared to 0.01 days in autumn. Event-wise estimates suggest that a divergence between male and female migratory schedules is initiated at departure from the main non-breeding area, thousands of kilometres from-, and several months prior to arrival at the breeding area. Duration of migration, flight speed during migration and spatial locations of stationary sites were similar between sexes. Our results reveal that protandry might arise from sex-differential migratory schedules emerging at the departure from the main non-breeding area in southern Africa and retained throughout spring migration, supporting the view that sex-differential selection pressure operates during spring migration rather than autumn migration.

Following ongoing technological advances, an increasing amount of full-year tracking data on individual migratory movements is becoming available. This opens up the opportunity to study how migration develops within individuals in consecutive years and the extent to which the migratory program is constrained. Such knowledge is essential for understanding the degree of individual flexibility during the annual cycle, which may help identifying potential bottlenecks, where the range of individual decisions is restricted. In this study, we investigate repeatability in time of a long-distance migratory songbird, the red-backed shrike Lanius collurio, tracked across consecutive years (n = 7). Furthermore, we explore the population variability and dependencies between consecutive events of departure and arrival throughout the annual cycle in this species (n = 15). We find that individuals show high repeatability in timing of departure from their two main non-breeding areas in sub-Saharan Africa. In contrast, low repeatability is found in timing of arrivals to stationary sites throughout the annual cycle. Population variation in timing of departure and arrival was similar across all events, ranging from 30 to 41 days, and was highly dependent on timing of preceding events. We conclude that timing of departures is the key event potentially controlled by the individual innate migration program, while arrivals are more flexible, likely dependent on the environmental conditions experienced en route in red-backed shrikes. Still, apparent flexibility in the individual schedule may be hampered by overall constraints of the annual cycle. The annual migration schedule of migratory animals is controlled by a combination of endogenous and exogenous factors. Understanding the temporal dynamics within and between individuals across the annual cycle is important to assess to which extent the migratory schedule is constrained in time. By using full-annual cycle tracking data of individual red-backed shrikes tracked across consecutive years, we find that individuals are highly consistent in their decision to depart from their main non-breeding areas in sub-Saharan Africa, whereas arrivals are less consistent throughout the annual cycle. Overall, the migration schedule is highly constrained across the annual cycle, with each arrival and departure event being dependent on the previous event. Our results suggest that departure decision is underlying endogenous control and that little flexibility is available throughout this complex migration system.

Species attributes are commonly used to infer impacts of environmental change on multiyear species trends, e.g. decadal changes in population size. However, by themselves attributes are of limited value in global change attribution since they do not measure the changing environment. A broader foundation for attributing species responses to global change may be achieved by complementing an attributes-based approach by one estimating the relationship between repeated measures of organismal and environmental changes over short time scales. To assess the benefit of this multiscale perspective, we investigate the recent impact of multiple environmental changes on European farmland birds, here focusing on climate change and land use change. We analyze more than 800 time series from 18 countries spanning the past two decades. Analysis of long-term population growth rates documents simultaneous responses that can be attributed to both climate change and land-use change, including long-term increases in populations of hot-dwelling species and declines in long-distance migrants and farmland specialists. In contrast, analysis of annual growth rates yield novel insights into the potential mechanisms driving long-term climate induced change. In particular, we find that birds are affected by winter, spring, and summer conditions depending on the distinct breeding phenology that corresponds to their migratory strategy. Birds in general benefit from higher temperatures or higher primary productivity early on or in the peak of the breeding season with the largest effect sizes observed in cooler parts of species' climatic ranges. Our results document the potential of combining time scales and integrating both species attributes and environmental variables for global change attribution. We suggest such an approach will be of general use when high-resolution time series are available in large-scale biodiversity surveys.

BACKGROUND: Colonic diverticular disease is a common disorder with increasing incidence in Western societies. The intestinal microbiome may be among etiological factors. Helicobacter pylori may protect against some intestinal diseases, and incidence of H. pylori is decreasing in Western societies. Thus, we aimed to determine whether H. pylori is associated to decreased prevalence of registered colonic diverticular disease.MATERIALS AND METHODS: In a historical cohort study, patients were enrolled from primary health care centers after urea breath test for H. pylori and then followed for a median of 6 years. The patient's diagnostic codes and country of birth were acquired from nationwide Danish administrative registries. We used logistic regression to compare prevalence and Cox regression to compare incidence of diverticular disease between H. pylori-positive and H. pylori-negative patients, adjusting for confounding variables.RESULTS: Patients infected with H. pylori had lower prevalence of colonic diverticular disease (0.87% vs 1.14%, OR=0.62, 95% CI: 0.50-0.78). This phenomenon was observed whether we studied all registered diagnoses or only cases registered as primary diagnoses at discharge. After urea breath test, we observed no statistical difference in incidence rates of diverticular disease.CONCLUSION: H. pylori is associated with reduced prevalence of colonic diverticular disease. The inverse association was absent after the urea breath test. Thus, we speculate that H. pylori may provide protection from colonic diverticular disease. Alternatively, H. pylori is a marker for other factors affecting disease development.

Background: Knowledge of spatiotemporal migration patterns is important for our understanding of migration ecology and ultimately conservation of migratory species. We studied the annual migration schedules of European nightjar, a large nocturnal insectivore and compared it with two other larger migratory insectivores, common swift and common cuckoo. All species breed in North Europe and winter in sub-Saharan Africa, but estimating their spatiotemporal non-breeding distributions from observations is complicated by the occurrence of similar local African species. We used geolocators to track the annual migrations of nightjars and swifts and compared these with satellite tracking of cuckoo migration. Results: Individuals of the three species migrated to wintering grounds centered in Central Africa, except some common swifts that remained in West Africa, crossing or circumventing the Sahara along different routes in spring and fall. Overall, all species showed similar regional and seasonal use of several stopover areas during migration. Among the three species, European nightjars and common cuckoos showed the most similar spatiotemporal migration patterns. The nightjars wintered in SW Central Africa and breeding and wintering made up by far the two longest stationary periods. Swifts were generally more mobile, and some individuals progressively visited areas further east in East Africa during winter and further west in West Africa on spring migration; this species also spent less time on stopovers, but more on wintering areas. Cuckoos were intermediate in their extent of movements. The speed of nightjar spring migration was equal to that of fall migration, in contrast to the two other species where spring return to breeding areas was faster. Conclusions: Ecological requirements are potentially useful for understanding spatiotemporal migration patterns and causes of declines in migratory species.

We describe a method and device (< 1.2 g) for recording, processing and storing data about activity and location of individuals of free-living songbirds throughout the annual cycle. Activity level was determined every five minutes from five 100 ms samples of accelerometer data with 5 s between the sampling events. Activity levels were stored on an hourly basis throughout the annual cycle, allowing periods of resting/sleep, continuous flight and intermediate activity (foraging, breeding) to be distinguished. Measurements from a light sensor were stored from preprogrammed key stationary periods during the year to provide control information about geographic location. Successful results, including annual actogram, were obtained for a red-backed shrike Lanius collurio carrying out its annual loop migration between northern Europe and southern Africa. The shrike completed its annual migration by performing > 66 (max. 73) nocturnal migratory flights (29 flights in autumn and > 37, max. 44, in spring) adding up to a total of > 434 (max. 495) flight hours. Migratory flights lasted on average 6.6 h with maximum 15.9 h. These flights were aggregated into eight travel episodes (periods of 4-11 nights when flights took place on the majority of nights). Daytime resting levels were much higher during the winter period compared to breeding and final part of spring migration. Daytime resting showed peaks during days between successive nocturnal flights across Sahara, continental Africa and the Arabian Peninsula, indicating that the bird was mostly sleeping between these long migratory flights. Annual activity and flight data for free-living songbirds will open up many new research possibilities. Main topics that can be addressed are e.g. migratory flight performance (total flight investment, numbers and characteristics of flights), timing of stationary periods, activity patterns (resting/sleep, activity level) in different phases of the annual cycle and variability in the annual activity patterns between and within individuals.

Background The use of biological therapy (biologicals) is established in the treatment of Crohn's disease. This study aimed to determine whether preoperative treatment with biologicals is associated with an increased rate of complications following surgery for Crohn's disease with intestinal anastomosis. Methods All patients receiving biologicals and undergoing abdominal surgery with anastomosis or strictureplasty were identified at six tertiary referral centres. Demographic data, and preoperative, operative and postoperative details were registered. Patients who were treated with biologicals within 2 months before surgery were compared with a control group who were not. Postoperative complications were classified according to anastomotic, infectious or other complications, and graded according to the Clavien–Dindo classification. Results Some 111 patients treated with biologicals within 2 months before surgery were compared with 187 patients in the control group. The groups were well matched. There were no differences between the treatment and control groups in the rate of complications of any type (34·2 versus 28·9 per cent respectively; P = 0·402), anastomotic complications (7·2 versus 8·0 per cent; P = 0·976) and non-anastomotic infectious complications (16·2 versus 13·9 per cent; P = 0·586). In univariable regression analysis, biologicals were not associated with an increased risk of any complication (odds ratio (OR) 1·33, 95 per cent confidence interval 0·81 to 2·20), anastomotic complication (OR 0·89, 0·37 to 2·17) or infectious complication (OR 1·09, 0·62 to 1·91). Conclusion Treatment with biologicals within 2 months of surgery for Crohn's disease with intestinal anastomosis was not associated with an increased risk of complications.

The migration strategies of smaller, south European, Mediterranean birds are less well known than those of northern and central European birds. We used geolocators to map individual spatiotemporal migration schedules of three species breeding in the Iberian Peninsula: the White-rumped Swift Apus caffer, rufous-tailed Scrub-robin Cercotrichas galactotes and Bluethroat Cyanecula svecica. The three species crossed the Sahara desert with a westward detour, to reach West African winter grounds in the Sahel (Bluethroats and Scrub-robins) or the rainforest belt (Swifts). Despite the proximity of the breeding grounds to the desert barrier, all but one individual stopped over before the desert crossing during autumn migration. After spending six months on average in sub-Saharan Africa with variable itinerancy, spring migration was faster overall and more direct than in autumn. Autumn migration was of similar duration to that found in related northern European migrants and therefore slower in southern birds. Spring migration was completed in less time than in the northern migrants (data only for Swifts and Scrub-robins). The shorter migration distance and proximity to the barrier potentially allow south European trans-Saharan migrants to migrate more slowly than northern migrants but only when less time-constrained in autumn.—Lomas vega, M., Willemoes, M., Arizaga, J., Onrubia, A., Cuenca, D., Alonso, D., Torralvo, C., Tottrup, A.P. & Thorup, K. (2019). Migration strategies of Iberian breeding White-rumped Swifts Apus caffer, rufous-tailed Scrub-robins Cercotrichas galactotes and Bluethroats Cyanecula svecica. Ardeola, 66: 51-64.

When patients present with malignant cologastric fistulas, the tumor stage is often advanced and management is only palliative. We report the case of a 75-year-old man with a symptomatic cologastric fistula arising from an advanced tumor in the transverse colon, previously stented owing to malignant obstruction. An 8-cm-long covered self-expanding metal stent (COMVI enteral colonic stent; Taewoong Medical) was placed inside the primary stent, which sealed the fistula and completely alleviated the symptoms. Considering the successful outcome, we propose that insertion of a covered stent be considered in the palliative management of patients with malignant cologastric fistulas.

Some species of long-distance migrant birds are thought to follow spatiotemporal patterns of high food availability during the non-breeding season, a strategy termed “itinerancy,” instead of being sedentary in one specific site. We tracked the migration of a small Eurasian songbird, the Common Redstart (Phoenicurus phoenicurus), using archival light-level geolocators. The birds showed a distinct counterclockwise loop migration from northern Europe. Fall migration passed west of the Mediterranean Sea and along the northwest African coast before the birds made an abrupt change of direction at the southern edge of the Sahara toward the winter area farther inland in the West African Sahel. Spring migration was more direct: north to the Iberian Peninsula and back to northern Europe. The birds spent more time in only one winter site than they do during the breeding season in northern Europe, and they generally showed no signs of itinerancy—except for one bird that probably avoided an exceptional droug...

Capsule Summer weather affects reproductive success in the Red-backed Shrike (Lanius collurio). Aims To investigate the relationship between reproductive success and weather conditions in the European breeding areas. Methods Using a Principal Component Analysis, we investigate how summer (July) weather affects reproductive success in two populations in northwestern Europe. Further, we assess the general relationship between reproductive success and weather in a review of published results. Results Weather is correlated with reproductive success in five out of six European populations, including the two populations at the northwestern range edge as well as three out of the four reviewed populations, all in central Europe. In general, sunny, warm and dry weather increases reproductive success, while rainy and cold weather has the opposite effect. Conclusion Our findings suggest that the warmer summers predicted under a future climate could increase the reproductive success of the Red-backed Shrike. Yet the ...

This study explores differences and consistencies between ring re-encounter and light-based geolocator data from Red-backed Shrike when used for studying three aspects of bird migration: departure direction and its relationship with longitude and latitude, non-breeding distribution, and timing of migration. Departure directions were consistent between the two methods. They indicate a funnel-shaped migration with individuals from southwest Europe taking a detour via the eastern Mediterranean rather than migrating via Gibraltar. This indicates that an original migration route has been retained after colonisation of the breeding range. Non-breeding distributions differed substantially between birds ringed and re-encountered and birds tracked by geolocators. This difference may be due to spatio-temporal heterogeneity in ring re-encounter probability and/or due to the two samples of birds belonging to different populations. The monthly average ring re-encounter location moved later southward during autumn and ...

Migratory birds track seasonal resources across and between continents. We propose a general strategy of tracking the broad seasonal abundance of resources throughout the annual cycle in the longest-distance migrating land birds as an alternative to tracking a certain climatic niche or shorter-term resource surplus occurring, for example, during spring foliation. Whether and how this is possible for complex annual spatiotemporal schedules is not known. New tracking technology enables unprecedented spatial and temporal mapping of long-distance movement of birds. We show that three Palearctic-African species track vegetation greenness throughout their annual cycle, adjusting the timing and direction of migratory movements with seasonal changes in resource availability over Europe and Africa. Common cuckoos maximize the vegetation greenness, whereas red-backed shrikes and thrush nightingales track seasonal surplus in greenness. Our results demonstrate that the longest-distance migrants move between consecutive staging areas even within the wintering region in Africa to match seasonal variation in regional climate. End-of-century climate projections indicate that optimizing greenness would be possible but that vegetation surplus might be more difficult to track in the future., K.T. thanks the Danish Council for Independent Research for support to the MATCH project (1323-00048B). K.T., A.P.T., M.W., M.L.V., M.B.A., and C.R. thank the Danish National Research Foundation for support to the Center for Macroecology, Evolution and Climate (DNRF96). H.P.D. and M.B.A. also acknowledge support from IC&DT Project (1/SAESCTN/ALENT-07-0224-FEDER-001755)., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

BACKGROUND: The potential advantages of robot-assisted laparoscopy are being increasingly investigated, although data on its efficacy in benign colorectal surgery are scarce.OBJECTIVE: We compared the early postoperative outcome in robot-assisted IPAA with open surgery procedures.DESIGN: This was an observational study based on prospectively collected data obtained from chart reviews.SETTING: The single-center data set covers patients operated on from January 13, 2004, to September 16, 2014, at a specialist center.PATIENTS: Patients with ulcerative colitis undergoing IPAA surgery were included.MAIN OUTCOME MEASURES: Study end points included the duration of operation, admission length, complications (Clavien-Dindo), reoperations, and readmissions.RESULTS: Eighty-one robot-assisted and 170 open IPAA procedures were performed. The duration of operation was significantly longer for robot-assisted laparoscopic procedures (mean difference, 154 minutes; CI, 140-170). During a mean follow-up of 102 days, no significant differences in the distribution of complications were found (Spearman p = 0.12; p = 0.07), and no postoperative deaths occurred in either group. Postoperative admission length was shorter following robot-assisted procedures (mean difference, -1.9; CI, -3.5 to -0.3), whereas 40% of patients were readmitted, compared with 26% of patients who had open surgery (OR, 1.9; CI, 1.1-3.4). Pouch failure occurred in 3 patients (1 following robot-assisted laparoscopy; 2 following open surgery). On multivariate regression analyses, robot-assisted laparoscopy was associated with a significantly longer duration of operation (mean difference, 159 minutes; CI, 144-174), and more readmissions for any cause (OR, 2; CI, 1.1-3.7).LIMITATIONS: This was a nonrandomized, single-center observational study.CONCLUSION: In this implementation phase, robot-assisted IPAA surgery offers acceptable short-term outcomes. The limitations of this observational study call for randomized controlled trials with long-term follow-up and exploration of functional results.

The small size of the billions of migrating songbirds commuting between temperate breeding sites and the tropics has long prevented the study of the largest part of their annual cycle outside the breeding grounds. Using light-level loggers (geolocators), we recorded the entire annual migratory cycle of the red-backed shrike Lanius collurio , a trans-equatorial Eurasian-African passerine migrant. We tested differences between autumn and spring migration for nine individuals. Duration of migration between breeding and winter sites was significantly longer in autumn (average 96 days) when compared with spring (63 days). This difference was explained by much longer staging periods during autumn (71 days) than spring (9 days). Between staging periods, the birds travelled faster during autumn (356 km d –1 ) than during spring (233 km d –1 ). All birds made a protracted stop (53 days) in Sahelian sub-Sahara on southbound migration. The birds performed a distinct loop migration (22 000 km) where spring distance, including a detour across the Arabian Peninsula, exceeded the autumn distance by 22 per cent. Geographical scatter between routes was particularly narrow in spring, with navigational convergence towards the crossing point from Africa to the Arabian Peninsula. Temporal variation between individuals was relatively constant, while different individuals tended to be consistently early or late at different departure/arrival occasions during the annual cycle. These results demonstrate the existence of fundamentally different spatio-temporal migration strategies used by the birds during autumn and spring migration, and that songbirds may rely on distinct staging areas for completion of their annual cycle, suggesting more sophisticated endogenous control mechanisms than merely clock-and-compass guidance among terrestrial solitary migrants. After a century with metal-ringing, year-round tracking of long-distance migratory songbirds promises further insights into bird migration.

Geographic variation in the population dynamics of a species can result from regional variability in climate and how it affects reproduction and survival. Identifying such effects for migratory birds requires the integration of population models with knowledge of migratory connectivity between breeding and nonbreeding areas. We used Bayesian hierarchical models with 26 years of Breeding Bird Survey data (1982-2007) to investigate the impacts of breeding- and nonbreeding-season climate on abundance of American Redstarts (Setophaga ruticilla) across the species range. We focused on 15 populations defined by Bird Conservation Regions, and we included variation across routes and observers as well as temporal trends and climate effects. American Redstart populations that breed in eastern North America showed increased abundance following winters with higher plant productivity in the Caribbean where they are expected to overwinter. In contrast, western breeding populations showed little response to conditions in their expected wintering areas in west Mexico, perhaps reflecting lower migratory connectivity or differential effects of winter rainfall on individuals across the species range. Unlike the case with winter climate, we found few effects of temperature prior to arrival in spring (March-April) or during the nesting period (May-June) on abundance the following year. Eight populations showed significant changes in abundance, with the steepest declines in the Atlantic Northern Forest (-3.4%/yr) and the greatest increases in the Prairie Hardwood Transition (4%/yr). This study emphasizes how the effects of climate on populations of migratory birds are context dependent and can vary depending on geographic location and the period of the annual cycle. Such knowledge is essential for predicting regional variation in how populations of a species might vary in their response to climate change.

Recent advances in tracking technology are based on the use of miniature sensors for recording new aspects of individual migratory behaviour. In this study, we have used activity data loggers with barometric and temperature sensors to record the flight altitudes as well as ground elevations during stationary periods of migratory songbirds. We tracked one individual of red-backed shrike and one great reed warbler along their autumn migration from Europe to Africa. Both individuals performed their migration stepwise in travel segments and climbed most metres during the passage across the Mediterranean Sea and the Sahara Desert and least metres during the first flight segment in Europe. The great reed warbler reached its highest flight altitude of 3950 m a.s.l. during the travel segment from Europe to west Africa, while the red-backed shrike reached 3650 m a.s.l as maximum flight altitude during its travel segment from Sahel to southern Africa. Both individuals used both lowlands and highlands for resting periods along their migrations. Furthermore, temperature decreased with increasing altitude during migratory flights for both individuals, highlighting the potential to determine flight duration from temperature measurements. Finally, we discuss how barometric data could be used to investigate birds’ responses to changes in air pressure as a cue for departures on migratory flights. This new technique, i.e. using a miniature data logger with barometric pressure sensor to estimate flight altitudes and ground elevations, will open up new avenues for research and importantly advance our understanding on how small birds behave during migratory flights. (Less)

Synopsis For many years, orientation in migratory birds has primarily been studied in the laboratory. Although a laboratory-based setting enables greater control over environmental cues, the laboratory-based findings must be confirmed in the wild in free-flying birds to be able to fully understand how birds orient during migration. Despite the difficulties associated with following free-flying birds over long distances, a number of possibilities currently exist for tracking the long distance, sometimes even globe-spanning, journeys undertaken by migrating birds. Birds fitted with radio transmitters can either be located from the ground or from aircraft (conventional tracking), or from space. Alternatively, positional information obtained by onboard equipment (e.g., GPS units) can be transmitted to receivers in space. Use of these tracking methods has provided a wealth of information on migratory behaviors that are otherwise very difficult to study. Here, we focus on the progress in understanding certain components of the migration-orientation system. Comparably exciting results can be expected in the future from tracking free-flying migrants in the wild. Use of orientation cues has been studied in migrating raptors (satellite telemetry) and thrushes (conventional telemetry), highlighting that findings in the natural setting may not always be as expected on the basis of cage-experiments. Furthermore, field tracking methods combined with experimental approaches have finally allowed for an extension of the paradigmatic displacement experiments performed by Perdeck in 1958 on the short-distance, social migrant, the starling, to long-distance migrating storks and long-distance, non-socially migrating passerines. Results from these studies provide fundamental insights into the nature of the migratory orientation system that enables experienced birds to navigate and guide inexperienced, young birds to their species-specific winter grounds.

Evidence for climate-driven phenological changes is rapidly increasing at all trophic levels. Our current poor knowledge of the detailed control of bird migration from the level of genes and hormonal control to direct physiological and behavioral responses hampers our ability to understand and predict consequences of climatic change for migratory birds. In order to better understand migration phenology and adaptation in environmental changes, we here assess the scale at which weather affects timing of spring migration in passerine birds. We use three commonly used proxies of spring-time climatic conditions: (1) vegetation "greenness" (NDVI) in Europe, (2) local spring temperatures in northern Europe, and (3) the North Atlantic Oscillation Index (NAO) as predictors of the phenology of avian migration as well as the strength of their effect on different subsets of populations and the dependence of correlations on species-specific migratory strategy. We analyze phenological patterns of the entire spring migration period in 12 Palaearctic passerine species, drawing on long-term data collected at three locations along a longitudinal gradient situated close to their northern European breeding area. Local temperature was the best single predictor of phenology with the highest explanatory power achieved in combination with NAO. Furthermore, early individuals are more affected by climatic variation compared to individuals on later passage, indicating that climatic change affects subsets of migratory populations differentially. Species wintering closer to the breeding areas were affected more than were those travelling longer distances and this pattern was strongest for the earliest subsets of the population. Overall, our results suggest that at least early subsets of the population are affected by local conditions and early birds use local conditions to fine-tune the date of their spring arrival while individuals arriving later are driven by other factors than local conditions e.g. endogenous control. Understanding what cues migratory organisms use to arrive at an optimum time is important for increasing our knowledge of fundamental issues like decision making in organisms during migration and is crucial for future protection of migratory organisms.

Loop migration among birds is characterized by the spring route lying consistently west or east of the autumn route. The existence of loops has been explained by general wind conditions or seasonal differences in habitat distribution. Loop migration has predominantly been studied at the population level, for example by analysing ring recoveries. Here we study loop migration of individual marsh harriers Circus aeruginosus tracked by satellite telemetry. We show that despite a generally narrow migration corridor the harriers travelled in a distinct clockwise loop through Africa and southern Europe, following more westerly routes in spring than in autumn. We used the Normalized Difference Vegetation Index (NDVI) to identify potential feeding habitat in Africa. Suitable habitat seemed always more abundant along the western route, both in spring and autumn, and no important stopover site was found along the eastern route. Observed routes did thus not coincide with seasonal variation in habitat availability. However, favourable habitat might be more important during spring migration, when the crossing of the Sahara seems more challenging, and thus habitat availability might play an indirect role in the harriers' route choice. Grid-based wind data were used to reconstruct general wind patterns, and in qualitative agreement with the observed loop marsh harriers predominantly encountered westerly winds in Europe and easterly winds in Africa, both in autumn and in spring. By correlating tail- and crosswinds with forward and perpendicular movement rates, respectively, we show that marsh harriers are partially drifted by wind. Thus, we tentatively conclude that wind rather than habitat seems to have an overriding effect on the shape of the migration routes of marsh harriers. General wind conditions seem to play an important role also in the evolution of narrow migratory loops as demonstrated for individual marsh harriers.

The onset of migration in birds is assumed to be primarily under endogenous control in long-distance migrants. Recently, climate changes appear to have been driving a rapid change in breeding area arrival. However, little is known about the climatic factors affecting migratory birds during the migration cycle, or whether recently reported phenological changes are caused by plastic behavioural responses or evolutionary change. Here, we investigate how environmental conditions in the wintering areas as well as en route towards breeding areas affect timing of migration. Using data from 1984 to 2004 covering the entire migration period every year from observatories located in the Middle East and northern Europe, we show that passage of the Sahara Desert is delayed and correlated with improved conditions in the wintering areas. By contrast, migrants travel more rapidly through Europe, and adjust their breeding area arrival time in response to improved environmental conditions en route . Previous studies have reported opposing results from a different migration route through the Mediterranean region (Italy). We argue that the simplest explanation for different phenological patterns at different latitudes and between migratory routes appears to be phenotypic responses to spatial variability in conditions en route .

Current climate change is affecting the timing of life-history events of birds, such as the timing of spring arrival at the breeding grounds. Interspecific differences in the advancement of spring migration have hitherto been attributed to differences in exposure to climatic variables in win- ter or on migration, without a more detailed consideration of sex-specific differences in the timing and extent of migration. Since males and females migrate during different times of the season or may segregate into different wintering grounds, we expect climate change to differentially affect the arrival timing of males and females. Furthermore, sexual selection theory predicts that the degree of protandry (i.e. the time difference between male and female arrival) should increase when the forces of natural selection opposing early arrival relax and the earliest males benefit from improved mating opportunities. Here, we explore whether the degree of protandry has changed during a period of climatic warming using long-term phenological data collected at 5 North European bird observato- ries. We show for 4 sexually dichromatic songbird species that spring migration has generally advanced, but that the degree of protandry has not changed. Moreover, we provide evidence that variation in large-scale weather conditions, as reflected in the North Atlantic Oscillation (NAO) index, have not affected the degree of protandry. We hypothesize that a parallel shift in the timing of male and female migration may be due to similar phenotypic plastic responses of males and females to climatic changes or reflect a correlated selection response in males and females. In addition, we discuss the possibility that the observed variation in protandry could result from seasonal shifts in local environmental conditions under which birds of both sexes 'fall out' and are sampled.

This study aims to investigate causes and mechanisms controlling protandrous migration patterns (the earlier breeding area arrival of males relative to females) and inter-sexual differences in timing of migration in relation to the recent climate-driven changes in phenology. Using standardised ringing data from a single site for eight North European migratory passerines collected throughout 22 years, we analysed sex-differentiated migration patterns, protandry and phenology of the entire populations. Our results show protandrous patterns for the first as well as later arriving individuals for all studied species. Males show more synchronous migration patterns compared to females and, hence, first arriving females followed males more closely than later arriving individuals. However, we found no inter-sexual differences in arrival trends as both sexes advance spring arrival over time with the largest change for the first arriving individuals. These findings seem in support of the “mate opportunity” hypothesis, as the arrival of males and females is strongly coupled and both sexes seem to compete for early arrival. Changes in timing of arrival in males and females as a response to climatic changes may influence subsequent mating decisions, with subsequent feedbacks on population dynamics such as reproductive success and individual fitness. However, during decades of consistent earlier spring arrival in all phases of migration we found no evidence of inter-sexual phenological differences.

Little is known about the factors influencing the breeding decisions of Arctic breeding seabirds and their behavior in a failed breeding year. Here we present the behavioral patterns observed in a year with late sea ice break-up and regular predator visits to the colony. We found that breeding initiation of Arctic Terns and Sabine’s gulls was delayed until the breeding attempt was given up and the colony abandoned. However, the birds did not leave the region but returned to the colony soon after sea ice break-up continuing bonding behavior although egg-laying was not initiated. In 2006, the period 11-15 July seemed important for the breeding decision, as birds gradually gave up breeding and left the colony during that period.

Dispersal is one of the key processes in shaping distributional ranges and community assemblages, but we know little about animal dispersal at the individual, population, or community levels, or about how dispersal correlates with the establishment and colonization of new areas. This is largely due to difficulties in studying individual movements at the relevant spatiotemporal scale, leading to a gap between the direct study of dispersal and our understanding of the build-up of larger-scale biodiversity. Recent advances in tracking technology make it possible to bridge this gap. We propose a way to link movement, dispersal, ecology, and biogeography. In particular, we offer a framework to scale-up from processes at the individual level to global patterns of biodiversity.

Males of most migratory organisms, including many birds, precede female conspecifics on their journey to the breeding areas. Several hypotheses have been proposed to explain the evolution of protandrous migration, yet they have rarely been tested at the interspecific level. Here, we provide correlational support for the “mate opportunity” hypothesis, which assumes that selection favours protandry in polygynous species where males gain significant fitness benefits from arriving earlier than females. Drawing on phenological data collected at two northern European stopover sites, we show that the time-lag in spring passage between males and females of five Palearctic migratory songbird species is positively associated with levels of extrapair paternity available from the literature. This suggests that males arrive relatively more in advance of females in species with high sperm competition where sexual selection through female choice is intense. Thus, protandry may arise from selection on the relative arrival timing of males and females rather than from selection within one of the sexes.

From 1976 to 1997 passerines were mist-netted and ringed on the island of Christianso, in the Baltic Sea. Here we present analyses of phenological changes (i.e. time of arrival) for 25 species based on the entire populations of mist-netted songbirds during spring migration. We used two approaches (least square and quantile regression) to test for changes in arrival time of first individuals and three different parts of the songbird populations (i.e. first 5%, 50% and 95% of the total number of trapped individuals corrected for trapping effort). Our results generally confirm earlier spring arrival of migratory passerines with an overall earlier arrival of 0.26 days per year. Changes in the arrival time of first individuals are often the only data available. They are typically analysed on the assumption that they are representative of their respective population. We found a unidirectional, significant change towards earlier arrival for all four measures of arrival timing which seem to support this. However, the four measures of arrival are changing at different rates. First individuals changed arrival time more rapidly than the first 5%, 50% and 95% of the spring total. Such differences are likely to be important for our understanding of population-dynamic changes in relation to climate change. These differences may also have long-term evolutionary consequences. Migration distance seems to affect the degree of change in arrival time, but we found no difference between species wintering in different regions of Africa.

We present a case of amoebic colitis, misdiagnosed as inflammatory bowel disease and treated with corticosteroids, leading to severe necrotizing enterocolitis. We review the literature on the epidemiology, pathogenesis, diagnosis, and treatment of amoebic dysentery, with special emphasis on the association between immunosuppressive treatment and the development of severe invasive amoebiasis.

Malignant atrophic papulosis (Degos' disease) is a very rare condition characterized by atrophic papular skin lesions and variable association of systemic involvement. We describe a 33-year-old man who presented with a widespread skin eruption consistent with malignant atrophic papulosis. During the course of the disease he even developed penile ulcerations, a symptom that has been reported only a few times previously. He subsequently died of multiple perforations of the small bowel 2.5 years after onset of the disease. Laboratory investigations revealed a mutation of factor V Leiden and the presence of lupus anticoagulant, but no anti-cardiolipin antibodies. The patient was treated with narrow-band ultraviolet (UV)B, prednisolone and, later, aspirin, pentoxifyllin and warfarin. Despite this very intensive anticoagulant and anti-platelet therapy, the treatment had no effect on the skin lesions and could not prevent systemic involvement.

Aim The study evaluated function and quality of life (QoL) in all patients having restorative proctocolectomy (RPC) in Denmark for ulcerative colitis (UC) from 1980 to 2010. Inclusion of all patients in one country has never previously been achieved. Method All patients who had had a RPC in Denmark, from the first case in 1980 to the last case in 2010, were studied. A cross-sectional questionnaire survey was performed, and function and QoL were assessed using a standardized questionnaire – the Short-Form 36 (SF36) – and the inflammatory bowel disease questionnaire (IBDQ). Results The median duration of follow up was 11 (range, 1–30) years. Apart from deaths, pouch failures and research protection, data on function and QoL were obtained from 1047 (85%) of 1229 patients who had a functioning pouch at the time of the investigation. More female patients than male patients experienced urgency (56% vs 44%, P = 0.0021). The median number of bowel movements per 24 h was 7 (range, 1–23) in female patients and 6 (range, 1–20) in male patients (P

The timing of migration is generally considered of utmost importance for reproduction and survival, and timing is furthermore considered to be under strong genetic control. The individual timing of migration is presumably a result of a combination of genetic, phenotypic and environmental factors as well as some degree of randomness. However, potential differences in consistency of timing between spring and autumn and between migration strategies are not well studied. Using long-term Danish ringing data, we study such differences by correlating date of ringing with date of recaptures for a suite of common migrating passerines in Denmark. We found that individuals marked early in one year tended to be recaptured early in the same season in a following year indicating that individuals time their migration in spring or autumn similarly between years. The relationship between spring and autumn migration was overall slightly negative, suggesting that birds arriving early in spring tended to depart late in autumn and vice versa. There were only weak effects of geographical location on timing, suggesting that the patterns found are not primarily caused by different populations being involved. Knowledge of individual consistency in migration timing is needed for understanding changes in migration timing. The consistent patterns of repeatabilities within and between seasons found here highlight the importance of timing of migration in songbirds.

Despite an overall advancement in breeding area arrival, one of the latest spring arrivals in northwest Europe since 1950 of several trans-Saharan songbird species occurred in 2011. Year-round tracking of red-backed shrikes and thrush nightingales revealed that the cause of the delay was a prolongation of stopover time during spring migration at the Horn of Africa, which was affected by extreme drought. Our results help to establish a direct link at the individual level between changes in local climate during migration and arrival and breeding condition in Europe thousands of kilometers further north.

1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit internal anal sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit internal anal sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum internal anal sphincter.

Left-sided colonic and rectal ischemia is commonly seen after surgery for ruptured abdominal aortic aneurysms (rAAAs) and is associated with increased mortality. Earlier studies have shown that flexible sigmoidoscopy (FS) may detect ischemia when performed postoperatively, and suggestions have been made that patients can be selected for FS based on clinical and biochemical parameters. We sought to perform FS in all patients surviving the first 24 hours after surgery for rAAA and to compare the findings of FS to clinical and biochemical parameters.All patients undergoing emergency surgery for rAAA and surviving the first 24 hours underwent FS to assess any degree of ischemia.During the study period, 41 patients survived the first 24 hours after surgery. In 9 (22%) patients, some degree of colonic ischemia was found. Segmental necrosis was only shown in 5% at first FS. Patients with ischemia received more blood transfusions intraoperatively than those with normal findings at FS. They also had longer periods with mean blood pressure60 mm Hg postoperatively, and lower arterial pH on the first postoperative day. Blood lactate levels did not differ between the groups. None of the parameters were sufficiently discriminative to be used for distinguishing between patients with and without ischemia.Severe colonic ischemia was less common than previously reported. All cases of colonic ischemia were identified by early FS, but none of the clinical and biochemical parameters were sufficiently reliable to distinguish between patients with and without ischemia. It is suggested that all patients initially surviving surgery for rAAA should be offered FS to screen for colonic ischemia.

The purpose of the study was to compare the effect of transmural field stimulation (TMS) on isolated smooth muscle strips from rabbit sphincter of Oddi (SO), duodenal circular layer (Dc) and duodenal longitudinal layer (D1). The strips were suspended in thermostatically controlled 5-ml organ baths containing Krebs solution constantly bubbled with 5% CO2 in O2. TMS was delivered through platinum electrodes (140 V, 0.4 ms, 5 s trains, 40 Hz). The TMS responses could be divided in two main responses: (1) contraction initiated after cessation of the stimulus train, preceded by an inhibitory phase during TMS ('off'); and (2) contraction initiated during TMS ('duration'). The 'duration' response was observed in one out of 20 strips in the SO and Dc compartments, whereas 11 D1 strips (55%) showed 'duration' responses (P

To what degree juvenile migrant birds are able to correct for orientation errors or wind drift is still largely unknown. We studied the orientation of passerines on the Faroe Islands far off the normal migration routes of European migrants. The ability to compensate for displacement was tested in naturally occurring vagrants presumably displaced by wind and in birds experimentally displaced 1100 km from Denmark to the Faroes. The orientation was studied in orientation cages as well as in the free-flying birds after release by tracking departures using small radio transmitters. Both the naturally displaced and the experimentally displaced birds oriented in more easterly directions on the Faroes than was observed in Denmark prior to displacement. This pattern was even more pronounced in departure directions, perhaps because of wind influence. The clear directional compensation found even in experimentally displaced birds indicates that first-year birds can also possess the ability to correct for displacement in some circumstances, possibly involving either some primitive form of true navigation, or ‘sign posts’, but the cues used for this are highly speculative. We also found some indications of differences between species in the reaction to displacement. Such differences might be involved in the diversity of results reported in displacement studies so far.

In human penile corpus cavernosum strips, pre-contracted by noradrenaline, electrical stimulation of nerves evoked non-adrenergic, non-cholinergic (NANC) relaxant responses which could be inhibited by tetrodotoxin 10-6 M, NG-nitro-L-arginine (L-NNA) 10-7-10-4 M, and oxyhaemoglobin 10-5 M, but not by methylene blue (MB) 10-5 M. Acetylcholine-induced relaxations were also inhibited by L-NNA 10-4 M and oxyhaemoglobin 10-5 M, but were unaffected by pyrogallol 10-4M, MB 10-6 M, and tetrodotoxin 10-6 M. MB 5 × 10-4-10-4 M significantly reduced the responses to both electrical stimulation and to acetylcholine. Nitric oxide (NO) 10-7-10-4 M and sodium nitroprusside 10-9-10-4 M caused concentration-dependent relaxations. The NO-induced relaxations were inhibited by oxyhaemoglobin 10-5 M, and the concentration-response curve for sodium nitroprusside was shifted to the right by MB 10-5 M. The response to sodium nitroprusside was unaffected by L-NNA 10-4 M, oxyhaemoglobin 10-5 M, and pyrogallol 10-4M. In circumflex veins, pre-contracted by noradrenaline, no NANC-mediated relaxation was found in response to electrical stimulation; acetylcholine caused endothelium-dependent relaxations, which were insensitive to L-NNA 10-4 M and oxyhaemoglobin 10-5 M. NO and sodium nitroprusside caused concentration-dependent relaxations; the concentration-response curves for NO and sodium nitroprusside were shifted to the right by oxyhaemoglobin 10-5 M. Removal of the endothelium left the NO- and sodium nitroprusside-induced relaxations unchanged. The results confirm previous observations that relaxations of human corpus cavernosum induced by both NANC nerve stimulation and exogenous acetylcholine involve an agent derived from L-arginine. No NANC response to electrical stimulation was found in circumflex veins, where acetylcholine induced an endothelium-dependent relaxation, apparently independent of the L-arginine/nitric oxide pathway.

The passive and active length-tension relations of the circular smooth muscle layer of the human distal rectum and the proximal and distal internal anal sphincter were investigated. Muscle strips were prepared and mounted in organ baths for recording of isometric tension. Resting lengths (LR) were measured, and the preparations were elongated stepwise. At each length, the corresponding values for passive tension, spontaneous active resting tension, and the submaximal active tension were recorded. Elongations of 200-380% of LR were possible before a sharp increase in passive tension occurred. None of the mean tension values measured at length for maximal active tension (LO) differed significantly among the three muscle types. All strips developed active resting tension. This tension was myogenic and contributed 10 +/- 3, 23 +/- 6, and 27 +/- 6% to the total active performance of rectal and proximal and distal sphincter preparations, respectively. Collagen constituted approximately 50% of smooth muscle biopsies, with highest contents in distal internal anal sphincter. This study provides an acceptable method for assessing the optimal experimental length by stretching the strips in an inactive state to 200% of LR, followed by individual adjustment of the passive tension to 5 mN/mm2 measured at 200% of LR

With great interest we have read the paper by Rungoe et al 1 describing a possible decrease rate in surgery in patients with IBD. The authors have identified all Danish patients with IBD by their first IBD diagnosis registered in the time period from 1979 to 2011. Data were extracted from the Danish National Patient Register, which contains information about all inpatient hospital contacts including diagnoses and surgical interventions, and outpatient diagnoses were not registered before 1995. Accordingly, Cohorts 1 and 2 represent only patients, who have had conditions requiring first time admissions, whereas Cohorts 3 and 4 represent a mixture of patients having first time diagnoses of IBD as inpatients or as outpatients (probably milder cases). Thus, Cohorts 3 and 4 might represent patients with less severe disease at …

Control of bowel effluents is imperative in cases of postoperative bowel perforation, and this is best achieved by stoma formation. When stoma formation is impossible, the surgeon is often left with less optimal choices. We have used a Foley catheter enterostomy to provide source control in difficult cases of bowel perforation, and the details are reviewed in this report.Three patients underwent reoperation for postoperative bowel perforation. Two patients had leaking ileocolic anastomoses, and one patient had a leak from a serosal tear. In all cases a Foley catheter enterostomy was constructed at the point of the leak. The balloon was filled with 3 ml of saline, and the affected bowel segment was fixed to the inside of the abdominal wall by a purse-string suture supplied with a few additional stitches. Moreover, gentle traction was applied to the balloon by external suture fixation of the catheter.Immediate control of bowel effluents from the leak was achieved in all cases. Early enteral feeding was possible in two of the three patients, and the catheter was removed after 17-28 days. Drainage of bowel contents from the catheter wounds stopped within 2 days.This report demonstrates an effective and safe technique for sealing a postoperative bowel perforation with a Foley catheter enterostomy. It is useful in cases where a stoma cannot be brought out. The technique provides immediate source control and enables early enteral feeding. The utility of the procedure may be limited when the defect is large, when the surrounding bowel wall lacks integrity, and when it is not possible to mobilize the affected bowel segment toward the inside of the abdominal wall without tension.

The presence of adult barnacles of Fistulobalanus pallidus (Darwin) and Fistulobalanus albicostatus (Pilsbry) attached to field-readable plastic leg rings on the Lesser Black-backed Gull Larus fuscus in Northern Europe is reported. L. fuscus is a long-distance palaearctic migrant, breeding in temperate areas spreading widely over inland and marine habitats outside the breeding season. The species is known to perform long-distance migration to Africa and the Middle East. Combining present knowledge on the birds' migratory pattern and the home range of the barnacle species, it is concluded that the cypris larvae of F. pallidus must have settled in African waters, whereas the area where F. albicostatus settled on the bird leg rings is less certain. The barnacles were of adult size and must thus have been attached for a period of no less than 2 months. More than 30 individual barnacles could occur together on a single field-readable plastic leg ring. The barnacles could therefore, if ported alive to a new area, reproduce successfully and thus either introduce the species or genetically affect other native populations. This may pose a new and wholly unexpected transportation pathway for barnacles as invasive species.

Smooth muscle strips representing the longitudinal and the circular muscle layers of the oesophageal body and the oesophagogastric junction of the human oesophagus were mounted in organ baths and isometric tension recorded. Transmural field stimulation was applied to strips from both layers of the oesophageal body and to strips from the longitudinal muscle layer of the oesophagogastric junction. This resulted in contractions after cessation of the stimulus train in circular muscle, and in contractions during stimulation in longitudinal muscle preparations. Indomethacin lowered active tension in strips from the circular muscle layer of the oesophagogastric junction, and decreased responses to transmural field stimulation in all strips from the longitudinal muscle layer. The response to transmural field stimulation was increased in strips from the circular muscle layer of the oesophageal body, suggesting an inhibitory function of endogenous prostanoids in this muscle layer. Prostaglandin (PG) F2 alpha and the thromboxane A2 mimic U-46619 increased the responses to transmural field stimulation in all muscle types and the active tension in circular muscle from the oesophagogastric junction. PGE1 and PGE2 increased the responses to transmural field stimulation strips from the longitudinal muscle layer. In circular muscle strips from the oesophageal body responses to transmural field stimulation were inhibited. PGE1 decreased active tension in circular muscle strips from the oesophagogastric junction, whereas PGE2 produced inconsistent effects. These results suggest a role of prostanoids in the regulation of neuromuscular function in the human lower oesophagus. Moreover, exogenous prostaglandins may modulate oesophageal motor function.

Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response.

Isolated smooth muscle preparations from the rabbit urethra precontracted with noradrenaline (10(-5) M), endothelin (10(-7) M), or arginine vasopressin (10(-7) M) responded to electrical field stimulation by frequency-dependent non-adrenergic, non-cholinergic relaxations, which could be blocked by tetrodotoxin (10(-6) M). Relaxation was more pronounced in preparations precontracted by endothelin than by noradrenaline or arginine vasopressin. The electrically induced relaxations were reduced in a concentration-dependent manner by pretreatment for 30 minutes with NG-nitro-L-arginine (10(-6) to 10(-4) M) and NG-monomethyl-L-arginine (10(-5) to 10(-4) M). At the highest concentration of NG-nitro-L-arginine used (10(-4) M), relaxation was abolished and/or changed into a contraction. The effect of NG-nitro-L-arginine was reversible. NG-nitro-D-arginine had no effect. Pretreatment for 30 minutes with L-arginine (10(-3) M) slightly, but significantly, enhanced the maximum relaxation to field stimulation in noradrenaline-precontracted preparations. L-arginine pretreatment also prevented the effects of low, but not high, concentrations of NG-nitro-L-arginine. In contrast, D-arginine had no effect. Electrically induced relaxations were not significantly affected by methylene blue (10(-5) M) or superoxide dismutase (20 U/ml). Addition of nitric oxide (present in acidified solution of NaNO2) caused transient and concentration-dependent relaxations in preparations precontracted by noradrenaline. At the maximum concentration used (10(-3) M), the relaxant response averaged 67% of the tension induced by noradrenaline. Nitric-oxide-induced relaxations were not affected by NG-nitro-L-arginine or L-arginine, but were significantly inhibited by methylene blue. In preliminary experiments, effects similar to those found in rabbit urethra were also observed in isolated urethral preparations obtained from three patients. It is suggested that in the urethra, nitric oxide is involved in the mediation of relaxation evoked by electrical stimulation of nerves.

Niels Christian Bjerregaard1, Anders Tøttrup1, Henrik Toft Sørensen2, Søren Laurberg11Department of Surgery P, Aarhus Sygehus, Aarhus University Hospital, Tage-Hansens Gade 2, 8000 Aarhus C, Denmark; 2Department of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, 8200 Aarhus N, DenmarkBackground: In 2002, a new diagnostic strategy in symptomatic outpatients without known established colorectal cancer risk factors aged 40 years or older was implemented in Denmark. Fecal occult blood test (Hemoccult Sensa®) was a part of that strategy in patients without visible rectal bleeding.Aims: The aim was to assess the validity of the Hemoccult Sensa® test in detecting colorectal cancer in the above-mentioned outpatients.Patients: Symptomatic outpatients without known established colorectal cancer risk factors and without visible rectal bleeding.Methods: Hemoccult Sensa® was performed before endoscopic examination. Colorectal cancer was identified at histopathological examination. Patients completed a questionnaire about their symptoms before their first hospital appointment.Results: Eight of 256 patients were found to have colorectal cancer. Median patient age was 63 years. The positive predictive value, negative predictive value, sensitivity, and specificity of Hemoccult Sensa® for colorectal cancer were 10.5% (95% confidence interval [CI]: 6.8–14.3), 99.0% (95% CI: 97.8–100.0), 75.0% (95% CI: 69.7–80.3), and 79.4% (95% CI: 74.5–84.4).Conclusions: Hemoccult Sensa® as the initial examination in symptomatic outpatients without known established colorectal cancer risk factors presenting without rectal bleeding has to be used with caution. We did not find Hemoccult Sensa® test to be an acceptable alternative to flexible sigmoidoscopy.Keywords: colorectal neoplasms, occult blood, diagnostic tests, sensitivity, specificity

1. The role of the L-arginine-nitric oxide pathway in lower oesophageal sphincter (LOS) relaxation and oesophageal peristalsis was investigated. 2. Twenty four adult opossums were anaesthetized and the right vagus nerve was isolated in the neck and sectioned. Electrical stimulation, applied to the peripheral end of the nerve, resulted in a frequency-dependent relaxation of the LOS, and peristaltic and non-peristaltic contractions in the oesophageal body. 3. N omega-nitro-L-arginine (L-NNA, 10(-8)-10(-5) mol kg-1), an inhibitor of the L-arginine-nitric oxide pathway, inhibited LOS relaxation in a dose-dependent manner, but did not affect resting LOS pressure. At the highest dose of L-NNA no relaxation of the LOS was elicited in response to vagal stimulation. The effect of L-NNA, (10(-5) mol kg-1) was fully reversed by infusion of 10(-4) mol kg-1 L-arginine. Peristaltic velocity and amplitude of contractions in the oesophageal body were unaffected by L-NNA. 4. Infusion of sodium nitroprusside reduced LOS pressure to zero, and the drug was equally potent in control animals (-log ED50:8.1 +/- 0.2 mol kg-1) and in animals pretreated with L-NNA (-log ED50:8.2 +/- 0.3 mol kg-1). This suggests that the effect of L-NNA was not directly on guanylate cyclase. 5. A significant elevation of blood pressure was recorded after administration of L-NNA (10(-5) mol kg-1). 6. It is suggested that the L-arginine-nitric oxide pathway plays an important functional role for relaxation of the LOS, but not for oesophageal peristalsis. Whether the active substance is nitric oxide or a related nitroso-compound remains to be settled.

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.

Circular muscle strips from the opossum esophageal body obtained 3–5 cm above the esophagogastric junction were suspended in organ baths for measurement of isometric tension. Stimulation of nonadrenergic, noncholinergic (NANC) inhibitory nerves was performed using transmural field stimulation (TMS). During TMS, no mechanical response was elicited. After cessation of the stimulus a short period, also without mechanical response, intervened, and this period is called latency. The latency was followed by the ‘off-contraction. In control preparations, the latency and the amplitude of the ‘off-contraction were 1.47 ± 0.17 s, and 3.8 ± 0.9 mN, respectively. The inhibitor of the L-arginine-nitric oxide (NO) pathway, NG-nitro-L-arginine (L-NNA) concentration-dependently reduced the latency at concentrations > 10-6M (n = 6-7). At the highest concentration of L-NNA (10-4M), ‘off contractions were no longer seen. In 5 out of 7 preparations exposed to L-NNA (10-4M), a small contraction was seen during stimulation, and this contraction was abolished by atropine (10-6M) in all strips. L-NNA concentration-dependently reduced the amplitude of contractions at concentrations > 10-6M (n = 6–7). At 10-4M, the amplitude was reduced to 3 ± 2% of that of the initial contraction. Preincubation with L-arginine (10-5M) had no influence on the latency. The effects of L-NNA on both latency and the amplitude of contraction were antagonized by preincubation with L-arginine (10-5M). Atropine (10-6M) had no effect on the amplitude of the ‘off-contraction in control preparations. In conclusion, the L-arginine-NO-generating pathway plays an important role in determination of latency and therefore in the timing of the ‘off-contraction. The ‘off-contraction seems to be a rebound phenomenon.