Cool birds: first evidence of energy-saving nocturnal torpor in free-living common swifts Apus apus resting in their nests.

Daily torpor is a means of saving energy by controlled lowering of the metabolic rate (MR) during resting, usually coupled with a decrease in body temperature. We studied nocturnal daily torpor under natural conditions in free-living common swifts Apus apus resting in their nests as a family using two non-invasive approaches. First, we monitored nest temperature (Tnest) in up to 50 occupied nests per breeding season in 2010-2015. Drops in Tnest were the first indication of torpor. Among 16 673 observations, we detected 423 events of substantial drops in Tnest of on average 8.6°C. Second, we measured MR of the families inside nest-boxes prepared for calorimetric measurements during cold periods in the breeding seasons of 2017 and 2018. We measured oxygen consumption and carbon dioxide production using a mobile indirect respirometer and calculated the percentage reduction in MR. During six torpor events observed, MR was gradually reduced by on average 56% from the reference value followed by a decrease in Tnest of on average 7.6°C. By contrast, MR only decreased by about 33% on nights without torpor. Our field data gave an indication of daily torpor, which is used as a strategy for energy saving in free-living common swifts.

Prevalence of disorders in preweaned dairy calves from 731 dairies in Germany: A cross-sectional study.

The objective of this cross-sectional study was to determine the prevalence of disorders in preweaned calves in 3 regions in Germany, exemplary for structural diversity in dairy farming. A farm visit was performed on a single occasion on 731 dairy farms in the northern, eastern, and southern regions of Germany between December 2016 and July 2019. Farms differed in herd size, geographical location, and management. In the northern region, the farms had a median of 90 milking cows and were often run as full-time family businesses, partly with external workers. The eastern region tended to have larger farms (a median of 251 milking cows), which were often large-scale agricultural enterprises with employees. In the southern region, the farms had a median of 39 milking cows and were often traditional family businesses, some of these being part-time businesses. Clinical examinations were performed on 14,164 preweaned dairy calves (median 12 calves per farm) by trained veterinarians. A complete data set was available for 13,656 calves. Almost half (42.0%) of the evaluated calves were classified as being affected by at least 1 of the common calf disorders. Omphalitis (O, 20.9%; n = 2,876) and diarrhea (D, 18.5%; n = 2,670) were the most frequently recorded diagnoses, whereas respiratory diseases (RD) were observed to a lesser extent (8.7%; n = 1,100). A striking feature was the fact that 7.1% (n = 987) of the calves were affected by more than 1 disorder at the same time (multimorbidity, M). The following combinations of disorders were frequently observed: O and D (n = 596), O and RD (n = 164), and D and RD (n = 140). Disorders such as O and D, as well as M, were predominantly observed in calves aged 2 wk. A gradual increase in the frequency of RD was observed with age. For all disorders except RD, male calves were more often affected than females. Omphalitis was predominantly diagnosed in the summer months, whereas RD, D, and M were more common in the fall. We detected several statistically significant differences in the prevalence of clinical signs and disorders in preweaned dairy calves between the 3 exemplary regions. The prevalence of RD was higher in the south (10.8%) than in the north (8.2%) and east (7.4%). In the north (33.2%), O was observed more frequently than in the other regions (east: 18.9%; south: 10.5%), whereas D was found less frequently in the north (13.8%) than in the east (21.6%) and south (20.0%).

[Imaging of chronic inflammatory bowel diseases in childhood and adolescence : Repetitorium]. / Bildgebung chronisch-entzündlicher Darmerkrankungen im Kindes- und Jugendalter : Repetitorium.

Chronic inflammatory bowel diseases can already occur in childhood and in contrast to affected adults, are more frequently manifested as unspecific symptoms. Therefore, at the time of diagnosis the gastrointestinal tract may already be severely affected. Both the diagnostic methods and the treatment concept, which is ideally carried out by pediatric gastroenterologists, differ from those used in adults. The primary diagnostics mainly include sonography and hydro-magnetic resonance imaging (MRI), whereby each modality offers certain advantages depending on the patient and the examiner but is also subject to limitations in terms of feasibility and evaluation. Imaging diagnostics contribute not only to finding the diagnosis but also to assessing the extent of the disease. They also serve to monitor the course of the disease in terms of treatment response or failure, to assess the activity and to detect and quantify possible complications, such as fistulas or abscesses.

Holding tight to feathers - structural specializations and attachment properties of the avian ectoparasite Crataerina pallida (Diptera, Hippoboscidae).

The louse fly Crataerina pallida is an obligate blood-sucking ectoparasite of the common swift Apus apus As a result of reduction of the wings, C. pallida is unable to fly; thus, an effective and reliable attachment to their host's plumage is of utmost importance. The attachment system of C. pallida shows several modifications in comparison to that of other calyptrate flies, notably the large tridentate claws and the dichotomously shaped setae located on the pulvilli. Based on data from morphological analysis, confocal laser scanning microscopy, cryo-scanning electron microscopy and attachment force experiments performed on native (feathers) as well as artificial substrates (glass, epoxy resin and silicone rubber), we showed that the entire attachment system is highly adapted to the fly's lifestyle as an ectoparasite. The claws in particular are the main contributor to strong attachment to the host. Resulting attachment forces on feathers make it impossible to detach C. pallida without damage to the feathers or to the legs of the louse fly itself. Well-developed pulvilli are responsible for the attachment to smooth surfaces. Both dichotomously shaped setae and high setal density explain high attachment forces observed on smooth substrates. For the first time, we demonstrate a material gradient within the setae, with soft, resilin-dominated apical tips and stiff, more sclerotized bases in Diptera. The empodium seems not to be directly involved in the attachment process, but it might operate as a cleaning device and may be essential to maintain the functionality of the entire attachment system.

Hemodynamic Consequence of Different Pacing Modes after Aortic Valve Replacement.

OBJECTIVES: Ventricular pacemaker stimulation may cause deterioration of hemodynamics in patients with left-ventricular hypertrophy following aortic valve replacement. Since the diastolic function is often impaired, it remains unclear which heart rate best optimizes cardiac output. Low heart rates are suggested to treat impaired diastolic function chronically, but it is possible that cardiac output may be augmented by increasing the heart rate in patients with a fixed stroke volume (SV). The aim of this study is the identification of the best pacing mode and heart rate for the surrogate parameter SV and cardiac index(CI) in patients with left ventricular hypertrophy. METHODS: Various pacemaker stimulation modes and different heart rates, as well as their influence on hemodynamics, were tested following aortic valve replacement in 48 patients with severe left-ventricular hypertrophy (Intraventricular septum (IVS)>1.5 cm) and aortic stenosis. SV and cardiac output were recorded by pulse curve analysis. Four modes of stimulation (right ventricular pacemaker stimulation (DDDright), left ventricular pacemaker stimulation (DDDleft), biventricular pacemaker stimulation (DDDbi), atrial pacemaker stimulation (AAI)) were documented at five different rates (60, 80, 100, 120, 140 beats/min) and three different postoperative time points (intraoperatively, 3h and 24h postoperatively). RESULTS: The highest CI was found at linear rates between 60 to 140bpm. AAI was the best mode of stimulation in the majority of cases (35%), but in others, either left, right and/or biventricular stimulation was found to be better (15%). SV showed a u-shaped trend with a peak at 100 beats/min. CONCLUSION: An increase in the heart rate does not lead to a notable drop in SV postoperatively in left-ventricular hypertrophy; hence a rise in cardiac output can be anticipated up to a rate of 100 beats/min. A standardized response in terms of an ideal pacemaker stimulation mode could not be identified.

Prospective, Randomized Un-Blinded Three Arm Controlled Study in Coronary Artery Revascularization with Minimal Invasive Extracorporeal Circulation Systems (MiECC): Surrogate Parameter Analysis of Biocompatibility.

OBJECTIVES: Minimal extracorporeal circulation techniques and systems (MiECC) may reduce the negative side effects of conventional extracorporeal circulation (ECC). However, it is still unclear as to what this is caused by, the reduced priming volume and hemodilution, or the avoidance of blood-air contact and dispersion of mediastinal debris into the systemic circulation. The aim of the trial was the comparison of MiECC to an open ECC setup (openECC) or a system with reduced blood air and debris interaction (closeECC). Methods: In a prospective randomized trial, 72 patients (73 ± 5.3 years; 83% male) referred for coronary artery bypass graft (CABG) were randomly assigned either to MiECC (priming volume 550mL), closeECC, or openECC (priming volume 1250mL). The laboratory surrogate endpoints (renal function, inflammatory response, ischemia, coagulation, and hemolysis) and clinical data were measured at six different time points (T1-6). Results: Patients were comparable for all preoperative variables. The operation times (MiECC 261 ± 79min; openECC 264 ± 75min; closeECC 231 ± 68min) and perfusion times (MiECC 115 ± 49min; openECC353 107 ± 37min; closeECC 99 ± 22min) revealed a trend of faster performance in the closeECC group (P < .05). Pro-inflammatory cytokines, ischemia, and coagulation markers were significantly elevated postoperatively in all cardiopulmonary bypass types, and decreased to pre-baseline levels at discharge (T5) without identifiable statistical differences between the three study groups. Free-hemoglobin was not significantly increased by centrifugal pump or cell saver procedures. Significant intraoperative hemodilution effects due to the different priming volumes were demonstrated only at the end of operation (T2) (MiECC Hb 9.6 ± 1.1g/dL; openECC Hb 9.0 ± 0.8g/dL; closeECC Hb 8.7 ± 1g/dL; P =. 01). CONCLUSION: Neither the hemodilution, suction technique (MiECC), nor blood-air interface (closeECC) could show sustainable benefits in this underpowered study, compared to conventional ECC systems (openECC) in a high volume series of surrogate parameters.

Real-time measurement of rectal mucosal microcirculation during cardiopulmonary bypass.

OBJECTIVES: Mesenteric ischemia is still a fatal event after cardiac procedures. No adequate intraoperative methods are available to monitor the gastrointestinal mucosal microcirculation in real-time conditions. The aim of the study was to assess a newly designed microprobe using laser Doppler flowmetry and remission spectroscopy. DESIGN: One-group, prospective, nonrandomized, open, pilot diagnostic study. SETTING: Monocenter university hospital. PARTICIPANTS: 50 patients (n = 38 males, 67±6 years) scheduled for cardiopulmonary bypass (CPB) were prospectively included. INTERVENTION: During anesthetic induction, the transrectal microprobe (30×15 mm) was positioned between the inferior and middle rectal valve (5-8 cm). Time periods were summarized at T1 = pre-CPB, T2 = CPB, T3 = post-CPB. MEASUREMENTS AND MAIN RESULTS: In 39 of 50 patients, data recruitment with the microprobe was successful. Measurement failures were due to fecal contaminations and probe dislocations. Rectal blood flow and velocity significantly decreased after bypass initiation (T2). Lowest flow rates were recorded after cross-clamp removal and did not recover at the end of bypass (T3). No side effects of the probe were noted. CONCLUSIONS: The new microprobe allows reproducible, safe, intraoperative, real-time evaluation of the rectal mucosal microcirculation. It could be a useful diagnostic tool to prevent mesenteric ischemia by optimizing extracorporeal circulation in future studies. However, first correlation of rectal blood flow and postoperative events (eg, ischemia, lactate) in a large cohort are necessary.

Associated factors for non-ischemic serum myoglobin release after cardiac surgical procedures.

BACKGROUND: Myoglobin has become established as a serum marker of myocardial injury. However, myoglobin levels can increase exponentially without any correlation to postoperative clinical ischemia symptoms. In this retrospective study, we analyzed the associated factors for a non-ischemic myoglobin release. METHODS: We performed a data analysis from 532 consecutive cardiac surgery patients (2010 to 2011, 73% males; age 65 ± 11 years). Non-ischemic myoglobin elevation was defined as CK-MB <50 U/l and/or the absence of any ischemic clinical events (eg, myocardial infarction, mesenteric vascular occlusion). RESULTS: Using a multifactorial model, predictive elements and associated factors for non-ischemic myoglobin increase were male sex, ejection fraction < 30%, BMI > 30 and transfusions. Serum myoglobin was not significantly different in patients with high muscle mass. CONCLUSIONS: A non-ischemic serum myoglobin release is rare, but could be associated in subgroups of patients. Further investigations should focus on clinical targets, for example, concomitant medications for which our study was not powered.

Long-term follow-up of minimally invasive cardiac surgery using an endoaortic occlusion system.

OBJECTIVES: We reviewed the initial patient series (n=116) of our institution performing minimally invasive coronary artery bypass grafting (CABG) (n=79), mitral valve surgery (n=1), or atrial septal closure (ASD) procedures (n=26) using an endoaortic occlusion system. With this technique relevant intra-aortic pressures are exerted on the aortic wall during the clamping time. This might lead to late aortic degeneration and aneurysm formation. Our study sought to evaluate postoperative aortic complications and the quality of life (modified SF-12). METHODS: One hundred sixteen patients (56% male; 54 years ± 14.5; range 19 years to 77 years) underwent a cardiac procedure using an endoaortic clamp. The endoaortic balloon clamp catheter was used to occlude the ascending aorta at pressures >300 mmHg. Patients were rescheduled for echocardiographic examination after a mean follow-up period of 8.8 years. RESULTS: The analysis performed among 78 patients showed no incidence of any structural damage to the ascending aorta at the intraoperative position of the endoaortic balloon. The physical and mental summary scores are equal to those of comparable patient groups. CONCLUSIONS: The endoaortic occlusion system causes no damage to the aortic wall. If the system causes any problems, they occur immediately during surgery. Patients treated with this minimally invasive technique exhibited the same quality of life as those undergoing conventional surgery.

MRI identification of pseudolesions in the distal tibia articular surface: Frequency and diagnostic criteria.

OBJECTIVE: Pseudolesions of joints are known as focal irregularities of chondral or subchondral bone in typical joint areas and occur frequent but without clinical relevance. This study aims to report the prevalence and describe MRI findings of a previously unreported chondral, mostly posterior located pseudolesion of the distal tibia, and to define criteria to distinguish it from pathologic osteochondral lesions, as well as from another known pseudolesion of this area - the so called "Notch of Harty". MATERIAL AND METHODS: A tri-centric retrospective case-control study included a total of 2,428 patients with ankle MRI examinations performed over a period of 6 years. MRI scans were evaluated by three radiologists in consensus for any cartilage irregularity of the distal tibial articular surface. For this purpose, the tibial articular surface was divided into 9 topographic regions. Proton-density weighted, fat-suppressed sequences in sagittal and coronal acquisition were used to assess the postero-medial articular surface of the tibia. Imaging features such as size and localization of cartilage irregularity and/or a cortical mould as well as presence of associated edema and/or subchondral cysts were reported. Demographic data (sex, age, and weight) was also recorded. Clinical data comprised presence of pain, movement impairment, and concomitant pathologies. RESULTS: A total of 68 patients (34 male, 34 female) with a lesion of the distal tibia were identified that had a new pseudolesion (prevalence of 3%). These lesions occurred most frequently (50 out of 68, 74%) in the postero-medial distal tibia plafond and were more commonly detected in the age group of 9-30 years (47%). In 13 of these 68 cases, the cartilage irregularity was the sole lesion without subchondral abnormalities. By defining these cases as definite pseudolesions, the prevalence was 1% and their age distribution was similar to that of the 55 other lesions with subchondral changes. Here with 11 of the 13 cases the majority (85%) were seen in the posterior part, especially in the postero-medial part (55%) of the distal tibia. The size of the cartilage defect ranged from 1 to 7 mm, and the majority (69%) sized from 2 to 3 mm. In 36 of 68 patients, we have seen subchondral alterations such as edema and/or cysts in addition to cartilage irregularity. 66% (n = 45) of these changes were edema and 37% (n = 25) were cysts. None of these 68 new pseudolesions with or without subchondral changes needed surgical or arthroscopic intervention. In the radiological and orthopaedic reports, clinical symptoms such as pain or instability were never associated with our observed lesions and there was no significant correlation between the presence of motion-related pain and imaging findings of cartilage irregularity, subchondral edema, and subchondral cysts. Thirteen patients had MRI follow-up examinations. Here the lesions did not show any MR morphological changes or clinical deterioration. Besides the new pseudolesion, which occured mainly in the posterior part of the tibia surface, we observed the "Notch of Harty" with a higher prevalence (25%) in our patient cohort. The typical localization was in the antero-medial tibial articular surface, without any edema or cysts. There were no coincidences of patients with both a new pseudolesion and the "Notch of Harty" CONCLUSION: A new pseudolesion is typically seen in the postero-central and postero-medial tibial articular surface with a prevalence of 3% and may be associated with only a small cartilage irregularity. In many cases, however, additional findings such as bone edema and/or an adjacent bone cysts were found, which impairs differentiation of these lesions from pathologic osteochondral lesions. The latter are obviously often associated with a larger cartilage defect and clinical symptoms. Due to the balanced age distribution between those pseudolesions with and without subchondral changes and the lack of clinical symptoms, we conclude that the here reported pseudolesions are not a predilection for a clinically manifest osteochondral lesion (OCL). At the very least, the apparent lack of clinical relevance increases the likelihood that we are dealing with a new true pseudolesion.

Mid-term follow up of a novel bioprosthesis in aortic valve surgery.

BACKGROUND AND AIM OF THE STUDY: The BioPhysio bioprosthesis (Edwards Lifesciences LLC, Irvine, CA, USA) was designed to further improve the hemodynamic performance currently achieved by stented valves. A flexible Nitinol stent that preserves aortic root dynamics, thus maximizing the effective orifice area (EOA), is a key innovation of this prosthesis. The study aim was to provide a clinical evaluation of this new device. METHODS: Between December 2004 and August 2005, a total of 50 patients (27 males, 23 females; mean age 75.8 +/- 5.1 years; range: 55-84 years) received a BioPhysio aortic bioprosthesis. Clinical outcomes, EOAs, mean gradients and regression of left ventricular hypertrophy were evaluated echocardiographically at discharge, and at six, 12, 24, 36, 48, and 60 months after surgery. RESULTS: The 60-month follow up was complete for all patients. No patients died within 30 days of surgery, but the late mortality was 14% (n = 6). There was one sudden unexplained death. One patient developed endocarditis at two years after surgery and underwent reoperation. There were no cases of stroke or renal failure. The BioPhysio prosthesis showed a good hemodynamic performance, with a significant fall in mean gradient to 15.1 +/- 8.3 mmHg, a mean EOA of 1.5 +/- 0.7 cm2, and a mean ejection fraction of 61 +/- 7.2%. There were no cases of aortic regurgitation. The NYHA functional class was improved in all patients, and there was a significant reduction in the left ventricular mass index to 185.7 +/- 49.6 g/m2 at 24 months. CONCLUSION: The clinical performance of the BioPhysio aortic bioprosthesis is comparable to that of regular stentless aortic valves. However, clinical approval for the widespread use of this bioprosthesis was not obtained.

No "carry-over" effects of tracking devices on return rate and parameters determining reproductive success in once and repeatedly tagged common swifts (Apus apus), a long-distance migratory bird.

BACKGROUND: To understand life-history strategies in migratory bird species, we should focus on migration behaviour and possible carry-over effects on both population and individual level. Tracking devices are useful tools to directly investigate migration behaviour. With increased use of tracking devices, questions arise towards animal welfare and possible negative effects of logger on birds. Several studies were conducted to address this question in birds that were tagged and tracked for one complete non-breeding season including migration but with mixed results. To detect individual-based decisions regarding migration strategy, we need to track the same individuals several times. So far, there are no studies investigating effects of repeatedly tagging on reproduction and life-history traits in individual migratory birds, especially in small birds. METHODS: We used long-term data of 85 tagged common swifts (Apus apus), a long-distance migratory bird, of a breeding colony in Germany to test whether carrying a geolocator or GPS logger once or repeatedly during non-breeding season affected return rate, apparent survival, and parameters determining reproductive success. Additionally, we checked for individual differences in arrival date and breeding parameters when the same individuals were tagged and when they were not tagged in different years. Further, we calculated the individual repeatability in arrival at the breeding colony and date of egg laying in repeatedly tagged swifts. RESULTS: Once and repeatedly tagged birds returned to the colony at a similar rate as non-logger birds and arrived earlier than non-logger birds. We found no effect of logger-type on return rate in logger birds. We detected no differences in apparent survival, time lag to clutch initiation, date of clutch initiation, clutch size, number of chicks and fledglings between logger and non-logger birds. We found neither an effect of loggers nor of logger-types on the arrival date and breeding parameter on individual-level. Arrival date was highly repeatable and date of clutch initiation was moderately repeatable within repeatedly tagged individuals.

Diffusing capacities and ventilation: perfusion ratios in patients with the clinical syndrome of alveolar capillary block.

Studies were performed on 10 patients with the clinical syndrome of alveolar capillary block while each patient was breathing four different inspired oxygen mixtures. The data were interpreted using the principle of the Bohr integral isopleth with which alveolar oxygen tension in the differently ventilated parts of the lung can initially be treated as unknown. It is then possible to determine the distribution of ventilation, of perfusion, of diffusing capacity, of lung volume, and of alveolar and end capillary blood oxygen tension in the variously functioning parts of the lung. In two patients shunts were the major factor interfering with oxygen transfer. In four others inequalities in ventilation: perfusion ratios and in diffusing capacity in different parts of the lung were the factors interfering with oxygen transfer. In four more patients ventilation: perfusion ratios were the same throughout the lung, the only disturbance of oxygen transfer being in the total diffusing capacity or in its distribution between the different parts of the lung.

Early changes in gene expression and inflammatory proteins in systemic juvenile idiopathic arthritis patients on canakinumab therapy.

BACKGROUND: Canakinumab is a human anti-interleukin-1ß (IL-1ß) monoclonal antibody neutralizing IL-1ß-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). METHODS: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA). Changes in pro-inflammatory cytokines IL-6 and IL-18 were assessed up to day 197. RESULTS: Microarray analysis identified 984 probe sets differentially expressed (≥2-fold difference; P < 0.05) in patients versus controls. Over 50% of patients with ≥50 aACR JIA were recognizable by baseline expression values. Analysis of gene expression profiles from patients achieving ≥50 aACR JIA response at day 15 identified 102 probe sets differentially expressed upon treatment (≥2-fold difference; P < 0.05) on day 3 versus baseline, including IL-1ß, IL-1 receptors (IL1-R1 and IL1-R2), IL-1 receptor accessory protein (IL1-RAP), and IL-6. The strongest clinical response was observed in patients with higher baseline expression of dysregulated genes and a strong transcriptional response on day 3. IL-6 declined by day 3 (≥8-fold decline; P < 0.0001) and remained suppressed. IL-18 declined on day 57 (≥1.5-fold decline, P ≤ 0.002). CONCLUSIONS: Treatment with canakinumab in SJIA patients resulted in downregulation of innate immune response genes and reductions in IL-6 and clinical symptoms. Additional research is needed to investigate potential differences in the disease mechanisms in patients with heterogeneous gene transcription profiles. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00886769 (trial 1). Registered on 22 April 2009; NCT00889863 (trial 2). Registered on 21 April 2009.

[Long term follow-up after intracranial vertebro-basilar artery stenting]. / Langzeitergebnisse nach Behandlung intrakranieller vertebrobasilärer Stenosen mit Stents.

PURPOSE: Recurrent ischemic symptoms attributable to intracranial high-grade vertebrobasilar artery stenoses are associated with a high risk of ischemic stroke, particularly if these occur in spite of aggressive medical treatment. Long term efficacy data for endovascular stent angioplasty of symptomatic intracranial stenoses are lacking. The purpose of this prospective study is to determine the rates of deaths, of ischemic events and of restenosis during long-term follow-up. MATERIALS AND METHODS: Between June 2001 and February 2004 twelve patients (11 male, 1 female; median 63 yrs; range, 46 - 75 yrs) with recurrent ischemic symptoms attributed to > or = 70 % intracranial vertebro-basilar artery stenoses, who had failed aggressive medical treatment, were included. Median follow-up was 24 months (range: 6 to 36 months). Intracranial stenoses were measured using 3D rotation angiography data sets and treated with balloon expandable stents. All patients were scheduled for follow-up including clinical (Barthel Index) and transcranial Doppler examinations and intraarterial angiography at 6 months after intervention. Clinical outcome was defined as the rate of stroke in any vascular territory or death during follow-up. Vascular outcome was determined by the rate of in-stent restenosis 50 % on follow-up as examined by intraarterial angiography at 6 months or by transcranial color-coded duplex sonography. RESULTS: Stent placement was technically successful in all patients. No patient had further cerebral ischemic symptoms; two patients died (1 myocardial infarct, 1 sudden death) during follow-up of median 24 months. The degree of stenoses was reduced from median 81 % (range 69 - 94 %) to 19 % (range 10 - 36 %) immediately after stent placement and to 32 % (range 22 - 48 %) after 6 months. No restenosis > or = 50 % occurred during follow-up. CONCLUSION: Based on this limited series, we believe that in patients, with recurrent symptoms despite aggressive medical treatment, endovascular stent placement in intracranial high-grade vertebrobasilar artery stenoses can be an effective and safe treatment option.

Leukocyte-endothelial cell adhesion in spontaneously hypertensive and normotensive rats.

Although the etiology of hypertension-related organ damage remains poorly understood, it has recently been proposed that activated and adherent leukocytes may contribute to the pathogenesis of progressive organ injury in hypertension. The objective of this study was to determine whether the adherence and emigration of leukocytes in microvessels differ between spontaneously hypertensive and normotensive rats. Leukocyte adherence, rolling, and emigration as well as vessel diameter and erythrocyte velocity were monitored in mesenteric venules of age-matched normotensive and hypertensive rats. Measurements were obtained under baseline conditions and during superfusion of the mesentery with either platelet activating factor, leukotriene B4, or NG-nitro-L-arginine-methyl ester, an inhibitor of nitric oxide synthesis. Tissue-associated myeloperoxidase activity, an index of the total tissue granulocyte population, was measured in various tissues of normotensive and hypertensive rats. Systemic arterial pressure and the circulating polymorphonuclear leukocyte count were elevated in hypertensive relative to normotensive rats. The number of adherent and emigrated leukocytes under baseline conditions did not differ between normotensive and hypertensive rats. Although the nitric oxide synthase inhibitor caused a similar rise in leukocyte adherence and emigration in both rat strains, the adhesive interactions elicited by either platelet activating factor or leukotriene B4 were significantly blunted in hypertensive relative to normotensive rats. Flow cytometric analysis of whole-blood samples revealed a lower surface expression of CD11b/CD18 on leukocytes from hypertensive rats under stimulated conditions. Myeloperoxidase activity in mesentery and small and large intestine was low, whereas lung, spleen, and stomach values were high in hypertensive compared with normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population-based Caucasian cohort.

The beta3-adrenergic receptor (3-BAR) is assumed to play a role in the regulation of energy balance by increasing lipolysis and thermogenesis. A recently detected allelic polymorphism (Trp64Arg polymorphism) has been suggested to contribute to the development of obesity and non-insulin-dependent diabetes mellitus. We examined the prevalence of the two 3-BAR alleles in Germany and looked for associations between 3-BAR genotype and metabolic disorders (obesity and type 2 diabetes mellitus). From over 6450 participants in the Diabetomobile Study, a nationwide epidemiologic study on the prevalence of metabolic disorders (carried out from 1993 to 1996 in Germany), 1259 participants were randomly chosen. The 3-BAR genotype status was determined by 3-BAR gene-specific genomic PCR and consecutive restriction fragment length polymorphism analysis. The frequencies of the different genotypes in the examined cohort were as follows: Trp64/Trp64, 88.3%; Trp64/Arg64, 10.8%; and Arg64/ Arg64, 0.8%. No significant differences between the different genotypes were found when comparing age, body mass index, weight, total and high-density lipoprotein (HDL) cholesterol, fasting insulin, HbA11, and blood pressure; neither did the type 2 diabetes mellitus participants in the different genotype groups differ significantly in terms of age of diabetes onset or HbA11. This is the largest population-based study on the Trp64Arg polymorphism reported yet. The Arg64 allele of the 3-BAR gene was found commonly in Germany. In our cohort, no significant associations between the Arg64 allele and metabolic disorders (e.g. obesity, type 2 diabetes mellitus, dyslipidemia, or hypertension) were detected.

Heteromeric nature of glucocorticoid receptors.

The wild-type and a mutant receptor of S49.1 lymphoma cells have been shown by photoaffinity labelling to contain steroid-binding polypeptides of Mr 94 000 and 40 000, respectively. We investigated the molybdate-stabilized forms of these receptors and obtained Mr 325 000 and 285 000, respectively, by gel filtration and sedimentation analysis. Mild chymotrypsin treatment of the large wild-type receptor resulted in a form of about Mr 290 000 which contained a steroid-binding polypeptide of Mr 40 000. The data suggest that the high -Mr forms of glucocorticoid receptors are heteromeric in nature and contain one steroid-binding polypeptide per complex.

Subunit dissociation and activation of wild-type and mutant glucocorticoid receptors.

Apparent molecular weights of wild-type and nti ('increased nuclear transfer') mutant glucocorticoid receptors were obtained from Stokes radii and sedimentation coefficients. At low salt concentrations molecular forms of Mr 328,000 and 298,000 of the wild-type and mutant, respectively, were predominant. Increasing ionic strength resulted in receptor dissociation. Dissociated forms of Mr 130,000 and 63,000 of the wild-type and mutant, respectively, were obtained at 300 mM KCl and above. Some metal oxi-anions prevented dissociation. Receptor activation to allow DNA binding produced the dissociated forms which could be separated from non-activated receptors by filtration through DNA-cellulose or by DEAE-cellulose chromatography. Non-activated wild-type and nti receptors eluted from DEAE-cellulose under identical conditions while activated wild-type and nti receptors eluted differently. Partially proteolyzed wild-type receptors behaved identically to nti receptors. We conclude that the large forms of wild-type and nti receptors are heteromeric and contain only one hormone-building polypeptide per complex.