Images from the surface of asteroid Ryugu show rocks similar to carbonaceous chondrite meteorites.

The near-Earth asteroid (162173) Ryugu is a 900-m-diameter dark object expected to contain primordial material from the solar nebula. The Mobile Asteroid Surface Scout (MASCOT) landed on Ryugu's surface on 3 October 2018. We present images from the MASCOT camera (MASCam) taken during the descent and while on the surface. The surface is covered by decimeter- to meter-sized rocks, with no deposits of fine-grained material. Rocks appear either bright, with smooth faces and sharp edges, or dark, with a cauliflower-like, crumbly surface. Close-up images of a rock of the latter type reveal a dark matrix with small, bright, spectrally different inclusions, implying that it did not experience extensive aqueous alteration. The inclusions appear similar to those in carbonaceous chondrite meteorites.

COMETARY SCIENCE. The structure of the regolith on 67P/Churyumov-Gerasimenko from ROLIS descent imaging.

The structure of the upper layer of a comet is a product of its surface activity. The Rosetta Lander Imaging System (ROLIS) on board Philae acquired close-range images of the Agilkia site during its descent onto comet 67P/Churyumov-Gerasimenko. These images reveal a photometrically uniform surface covered by regolith composed of debris and blocks ranging in size from centimeters to 5 meters. At the highest resolution of 1 centimeter per pixel, the surface appears granular, with no apparent deposits of unresolved sand-sized particles. The thickness of the regolith varies across the imaged field from 0 to 1 to 2 meters. The presence of aeolian-like features resembling wind tails hints at regolith mobilization and erosion processes. Modeling suggests that abrasion driven by airfall-induced particle "splashing" is responsible for the observed formations.

A fixed-dose combination of low molecular weight heparin with dihydroergotamine versus adjusted-dose unfractionated heparin in the prevention of deep-vein thrombosis after total hip replacement.

The low dose heparin regimen (LDH) is not appropriate for prevention of intra- and postoperative thromboembolic complications in high risk patients, especially those undergoing elective hip replacement. Despite LDH prophylaxis, the incidence of deep-vein thrombosis (DVT) remains in a range of 20 to 35%. Adjusted-dose unfractionated heparin prophylaxis is thought to be one of the most effective regimens for thrombosis prophylaxis in this indication, but it requires two or three daily injections as well as precise monitoring of the activated partial thromboplastin time (aPTT). As an attractive alternative, we investigated the efficacy and safety of the low molecular weight heparin (LMWH) certoparin combined with dihydroergotamine (DHE) given once daily. In a randomised, open clinical trial, a total number of 305 patients undergoing total elective hip replacement were enrolled and divided into two groups, either receiving a fixed-dose combination of LMWH (3,000 IU) and DHE (0.5 mg) subcutaneously once daily, or adjusted-dose unfractionated heparin (UFH) subcutaneously every 8 h. The UFH dosage was adjusted daily to keep an aPTT of about 50 s. The aPTT was determined 3 h after the morning injection. During the study, the starting dose (15,000 IU/day) was increased to a plateau value of 28,800 +/- 7,150 IU/day (mean +/- SD) to maintain the aPTT in the prescribed range. The plateau value was achieved after 8 postoperative days. For analysis of efficacy 289 patients were evaluable. The occurrence of deep vein thrombosis was determined by bilateral ascending venography, which was performed on the same day in patients with clinical signs suggesting DVT; and in all remaining patients at the end of the prophylaxis period. Deep vein thrombosis was diagnosed in 17 of 142 patients (12.0%) treated with LMWH/DHE and in 13 of 147 patients (8.8%) treated with adjusted-dose UFH. Combined distalproximal thrombosis was more frequently in patients receiving UFH (n = 5; 3.4%) compared to the LMWH/DHE group (n = 2; 1.4%). These differences are statistically not significant. In the UFH group one case of non-fatal pulmonary embolism occurred. Both prophylaxis regimens were well tolerated; wound bleeding was observed in 8 (5.3%) patients in the LMWH group and in 6 (4.0%) patients in the UFH group. Intraoperative blood-loss volume (mean +/- SD) was 751 +/- 339 mL (LMWH/DHE) and 736 +/- 380 mL (UFH), whereas postoperative drain-loss volume (mean +/- SD) was found to be 523 +/- 333 mL (LMWH/DHE) and 581 +/- 404 mL (UFH). Whole blood transfusion volumes (mean +/- SD) were 570 +/- 202 mL (LMWH/DHE) and 748 +/- 455 mL (UFH). Additionally, red cell replacement volumes (mean +/- SD) were 804 +/- 435 mL (LMWH/DHE) and 720 +/- 328 mL (UHF). Revision of wound or additional drainage were necessary in 3 LMWH/DHE and 7 UFH patients. One patient needed reoperation due to bleeding, 3 (2.0%) had petechia and 1 exhibited an allergic exanthema, all of them in the UFH group. A slight erythema at the injection site was observed in 6 (3.9%) patients receiving LMWH/DHE. During the course of prophylaxis, injection hematomas were documented in 57.9% (LMWH/DHE) and in 61.4% (UFH) of the patients. All differences were statistically not significant. Single daily subcutaneous injections of LMWH/DHE appeared to be safe and efficacious compared to adjusted-dose UFH for prophylaxis of DVT in high-risk patients.

Ultrastructural calcium distribution and myocardial calcium content in human idiopathic dilated cardiomyopathy.

Myocardial calcium overload in chronic heart failure is still a debatable issue. The aim of this study was to investigate the myocardial calcium content and intracellular calcium distribution in end-stage dilated cardiomyopathy. The explanted hearts of 13 patients (9 male, 4 female, mean age 49 ± 12 years) undergoing heart transplantation because of end-stage dilated cardiomyopathy were examined. Samples were obtained from the right and left ventricular free wall and from the septum. Calcium and magnesium content were measured by atomic absorption spectrophotometry. Ultrastructural calcium distribution was examined in dilated cardiomyopathy using the phosphate-pyroantimonate method. Ultrastructural calcium distribution was also examined in left ventricular biopsies obtained from 3 patients (male, mean age 47 ± 3.6 years) with nonfailing hearts. The number of mitochondrial calcium precipitates was estimated morphometrically by a point counting method. Myocardial calcium and magnesium content in dilated cardiomyopathy did not differ significantly among the right and left ventricles and septum ranging from 8.5 to 10.8 mmol/kg dry weight. The phosphate-pyroantimonate method visualized calcium precipitates being confined to the sarcolemma, T-tubules, intercalated disks, and mitochondria in both nonfailing myocardium and dilated cardiomyopathy. Because mitochondria may act as buffers of cytoplasmic calcium, mitochondrial calcium precipitates served as a criterion for a possible cellular calcium overload. No differences in the amount of mitochondrial calcium deposits were observed between dilated cardiomyopathy and nonfailing hearts. The data suggest that there is no global myocardial calcium overload in human eng-stage dilated cardiomyopathy.

Calcium overload in human giant cell myocarditis.

Myocardial calcium overload was observed in a patient with giant cell myocarditis. The myocardial calcium content estimated by atomic absorption spectrophotometry amounted to 120 mEq/kg dry weight, and the von Kossa stain disclosed multiple foci with patchy calcifications of myocardial fibres. Cytochemical examination of the ultrastructural calcium localisation using the phosphate-pyroantimonate method showed considerable variation in the subcellular calcium distribution. In normal myocytes calcium precipitates were confined to the inner leaflet of the sarcolemma, T-tubules, intercalated disks, and sporadically to mitochondria. In contrast, extensive calcification of mitochondria and loss of sarcolemmal calcium was evident in necrotic myocytes. A number of grossly normal myocytes also showed an increase of calcium precipitates in slightly swollen mitochondria. These findings suggest that myocardial calcium overload in this case started in viable myocytes and was not merely a secondary phenomenon occurring after cell death.

Kinetics of melphalan leakage during hyperthermic isolation perfusion in melanoma of the limb.

The kinetics of melphalan leakage into the peripheral blood were studied in 21 patients undergoing hyperthermic isolation perfusion of the upper or lower limb as an adjuvant treatment in high-risk melanoma; in 5 patients cisplatin was added. The melphalan concentrations in the peripheral blood rose predominantly during the first 20 min of perfusion and levelled out to an apparent steady state of about 0.28 micrograms/ml in upper extremity perfusions, and 0.34 (without cisplatin) and 0.37 micrograms/ml (with cisplatin) in lower extremity perfusion. Erythrocytes labelled with technetium Tc 99m, which were added concomitantly with melphalan to the perfusion medium, appeared in the systemic circulation of the patients at an almost constant rate of 0.32% (lower and upper limb perfusions without cisplatin and 0.37% (with cisplatin) of total tracer/min. This perfusate flow rate indicated by labelled erythrocytes completely explained the leakage of melphalan from the perfusion circuit into the peripheral blood. Peak concentrations of melphalan in the peripheral blood were observed immediately after reconstitution of normal hemodynamic conditions once isolation perfusion had been terminated. This fraction of melphalan might originate from tissue-binding sites, but also from vascular compartments; therefore, a thorough washing-out procedure might minimize this effect.

Determination of erythrocyte-bound acetylcholinesterase activity for monitoring pyridostigmine therapy in myasthenia gravis.

Monitoring of pyridostigmine therapy in patients with myasthenia gravis is not routinely performed, since the daily pyridostigmine doses are adjusted to the patient's actual clinical status rather than to pyridostigmine plasma concentrations (PPC). Moreover, PPC determination is time-consuming and needs much technical equipment. Since pyridostigmine reversible blocks acetylcholinesterase (AChE) at the neuromuscular junction, we studied the correlation between the enzyme's blood activity (erythrocyte-bound AChE) and PPC, on the one hand, and between blood AChE activity and the clinical status of the individual patient, on the other. In five previously untreated patients with myasthenia gravis blood AChE activity decreased in accordance with the actual PPC after a single oral dose of 60 mg pyridostigmine (group A). Amelioration of the clinical status corresponded to the decrease of AChE activity in the same way. In another five patients, who were on stable pyridostigmine medication for at least 1 week, AChE activity and PPC were constant during the day (group B). Since it is easier to perform than PPC, our results suggest that the determination of AChE activity may be superior to measuring PPC for monitoring cholinesterase inhibitor therapy in selected cases.

Anticoagulant effects and tissue factor pathway inhibitor after intrapulmonary low-molecular-weight heparin.

The present study was designed to investigate the anticoagulant action of inhaled low-molecular-weight (LMW) heparin on the release of tissue factor pathway inhibitor (TFPI) and on antifactor Xa activity, Heptest, activated partial thromboplastin time (APTT) and thrombin clotting time (TCT) in healthy volunteers. 3000 IU (group 1), 9000 IU (group 2), 27,000 IU (group 3) or 54,000 IU (group 4) LMW-heparin were given to 20 healthy volunteers each at 4 weeks intervals by inhalation. For safety reasons a dose escalating design was chosen. APTT and TCT did not change after inhalation of any dose of LMW-heparin as well as all parameters in group 1. In group 2, Heptest coagulation times were prolonged from 18.7 +/- 2.0 s before to 26.1 +/- 5.2 s 6 h and 20.5 +/- 1.9 s 24 h after inhalation and the other parameters remained uneffected. In group 3, S2222 method and the protamine assay increased from 0.01 to about 0.1 IU/ml 6 h after inhalation and returned to normal values after 24 h. TFPI antigen increased from 74.1 +/- 13.9 to 80.5 +/- 14.2 ng/ml 3 h after inhalation. TFPI activity remained unchanged. Heptest coagulation values were prolonged to 42 +/- 7.6 s after 6 h and returned to normal within 72 h after inhalation. In group 4, the following changes were observed: antifactor Xa activity increased to 0.343 +/- 0.196 U/ml after 6 h and normalized after 72 h. The protamine assay detected 0.2 +/- 0.18 U LMWH/ml after 6 h, TFPI antigen increased to 103 +/- 17.9 ng/ml and TFPI activity to 1.14 +/- 0.23 U 3 h after inhalation. All tests were normal after 24 h. Heptest coagulation values increased to 77.5 +/- 11.8 s 6 h after inhalation and normalized after 144 h. The area under the activity time curve of the S2222 method and of the Heptest assay increased with increasing doses (r = 0.677 and r = 0.571), respectively. The calculated elimination half-life of the aXa-effect was 7.5 h using S2222-, Heptest- and protamine assays. The data demonstrate a resorption of LMW-heparin by intrapulmonary route in man. The dose to produce antifactor Xa levels, prolongations of Heptest coagulation values and in releasing TFPI is about ten-fold higher than after subcutaneous administration.

Comparison of 3,000 IU aXa of the low molecular weight heparin certoparin with 5,000 IU aXa in prevention of deep vein thrombosis after total hip replacement. German Thrombosis Study Group.

BACKGROUND: The aim of this randomized, double-blind and prospective clinical trial was to investigate whether an increase of the conventional daily dosage (3,000 IU aXa) of the low molecular weight heparin certoparin up to 5,000 IU aXa/day might lower the incidence of deep vein thrombosis (DVT) in patients undergoing elective hip surgery. METHODS: The main criterium of this trial was the incidence of DVT diagnosed by bilateral ascending venography, which was performed either if DVT was clinically suspected or in each remaining patient between the 12th and the 14th postoperative day. A total number of 172 patients were enrolled to receive the conventional dosage of 3,000 IU aXa (Mono-Embolex NM) and 169 patients to receive the high dosage form (5,000 IU aXa) once daily. The mean age (+/-SD) was 69.6+/-9.5 and 67+/-11.7 years. RESULTS: No relevant differences were found concerning predisposing risk factors. The duration of surgery was 93+/-25.2 and 88+/-21.4 min (mean+/-SD). Surgical type and approach were not different between the groups. Deep vein thrombosis was detected in 17 patients (9.9%) in the conventional dose group and in 16 patients (9.5%) in the high dose group (intent-to-treat analysis; n.s.). The rate of bleeding complications was not significantly different except the cell saver volumes (770+/-136 vs 475+/-186 ml; p<0.001). No significant difference was found in the serious adverse event reporting along the lines of EC-GCP (10 vs 8 events; p=0.65). CONCLUSIONS: This clinical trial confirmed that the conventional dosage (3,000 IU aXa/day) of certoparin ensures maximal antithrombotic activity.

COLUMBUS Orbital Facility and Automated Transfer Vehicle: a challenge for agency & industry.

Long term continuous operation of the COLUMBUS Orbital Facility (COF) flight- and ground segment requires continuous mission control and operations support capability to ensure proper operation and configuration of the COF systems in support of ongoing science and technology payloads. The ISS logistics scenario will be supported by the Automated Transfer Vehicle (ATV). These operational needs require the built-up of a new ground infrastructure in Europe and USA, enabling an efficient operations for preparation, planning and mission execution. The challenge for the European space community consists in the development and operation of a user friendly operational environment but keeping costs within budgetary constraints. Results of detailed definition studies performed by both agency and industry for the ground infrastructure indicate solutions to those technical and programmatic requirements by using of existing centers and facilities, re-use of C/D phase products (Hardware, Software) and COTS equipment to avoid costly new developments, using engineering expertise of the industrial personnel from flight element phase C/D. The concept for operations execution defines the task sharing between Operations Control Facilities (OCF), Operations Support Facilities and User Operations Sites. Operations support consists of on-line engineering support, off-line engineering support, payload integration, logistics support and crew training support performed by industry. DASA RI has made internal investments in organizational concepts for mission operations as well as in mission technologies and tools based on the standard COLUMBUS Ground Software (CGS) toolset and on knowledge based systems to enable an efficient industrial operations support. These tools are available as prototypes being evaluated in a simulated operational environment.

[Incidence and development of noticeable hip findings (the dysplasia complex) in newborn and young infants. Additional statistical analysis of the findings]. / Zur Häufigkeit und Entwicklung auffallender Hüftbefunde (Dysplasie-Komplex) bei Neugeborenen und Kleinkindern. Weitere statistische Analyse der Hüftbefunde.

Early signs of hip dysplasia in 7120 children (in the neonatal period asymmetry of the gluteal folds, Ortolani snap phenomenon and restricted abduction; subsequently, at about 6 weeks, asymmetry of the gluteal folds and restricted abduction) were statistically analyzed with regard to simultaneous occurrence and their prognostic value in confirming a hip dysplasia. The findings at 6 weeks were found to be more serious. Almost no significance can be attached to an isolated finding in the period following birth. Since the study covered several clinics, it was possible to compare findings from individual centers. It was found that they fell into four groups with different diagnostic preferences, despite the agreed uniform examination technique. Thus, almost all of the positive Ortolani findings were diagnosed at two of the 20 clinics taking part in the study. In the overall comparison the group of clinics which relied almost exclusively on asymmetry of the gluteal folds had the least prognostic success. The clinics with a higher proportion of positive Ortolani findings had better prognosis results, though the incidence of dysplasias was not increased.

[Incidence and development of noticeable hip findings (a dysplasia complex) in newborn and young infants]. / Zur Häufigkeit und Entwicklung auffallender Hüftbefunde (Dysplasie-Komplex) bei Neugeborenen und Kleinkindern.

Among 5338 infants in a DFG (German Research Association) priority program for prospective examination of pregnant women and neonates, asymmetry of the gluteal folds was found in approx. 12%. However this is of little diagnostic value for early diagnosis of hip dysplasia/luxation. The number of cases of restricted abduction found was even lower: in the period following birth it was 3.4%, from the 3rd to the 14th week. 12.7%. Ortolani's sign, including slightly positive and uncertain findings, was positive in 3.0% of the neonates; a hip dysplasia/luxation was diagnosed in 2.4% of the infants. The high percentage of suspected cases diagnosed, at 12.6%, is indicative of excessive diagnosis, even though this figure may already contain some oblique-presentation hips. Moreover, all the data are rendered relative by the differences in emphasis made by the 20 clinics taking part in the study; as a result the actual state and hence the uncertainty of early diagnosis of a hip dysplasia in practice are faithfully reflected. The results are compared with corresponding figures published by Barlow from a study of 9289 children.

Prospective study of suspected associations between certain drugs administered during early pregnancy and congenital malformations.

From 1964 to 1976, a cohort study was performed in West Germany to study the possible influence of various factors on pregnancy and child development. Results of the evaluation of 13,643 pregnancies are given with respect to possible teratogenetic effects of antiemetic drugs and sex hormones administered in early pregnancy. There was no evidence of an increased risk of major malformations following the intake of certain antiemetic drugs and progesterone. Also, the use of a hormonal pregnancy test was not significantly associated with an increase of major malformations.

[Quantitative determination of total urinary protein utilizing the principle of Coomassie Brilliant Blue G250 binding to protein (author's transl)]. / Quantitative Proteinbestimmung im Harn mit dem Proteinbindungsfarbstoff Coomassie Brilliant Blau G250.

Coomassie Brilliant Blue G250 was used for the determination of total urinary protein and compared with the biuret-procedure. In the Coomassie Brilliant Blue G250-assay 0.10 ml urine are added to 5.0 ml Coomassie Brilliant Blue G250 reagent and the sample is read against the reagent blank. The Coomassie Brilliant Blue G250 method seems to be superior to the biuret-procedure because of better reproducibility, higher sensitivity and simpler handling. The upper limit or urinary protein excretion in 49 healthy subjects was 120 mg/24 h. To evaluate the clinical significance of the Coomassie Brilliant Blue G250 method the urinary protein concentration of 134 patients with metabolic, systemic and organ diseases was compared with the biuret-procedure. The regression line was y = 0.827 X + 8.713 mg/l with a correlation coefficient of r = 0.966. The type of proteinuria (mixed, glomerular, tubular) had no influence on the protein value measured with the Coomassie Brilliant Blue G250 method. However in selective proteinuria, like Bence-Jones protein excretion, there is no correlation between the two methods, because the concentration of Bence-Jones protein is underestimated. Lower protein values were also frequently obtained for patients with diabetes mellitus. Some specimens from patients with chronic renal failure treated by haemodialysis showed elevated values. In spite of these limitations the Coomassie Brilliant Blue G250 method might become the method of choice for the determination of total urinary protein.

Rhabdomyolysis after suicidal ingestion of an overdose of caffeine, acetaminophen and phenazone as a fixed-dose combination (Spalt N).

Rhabdomyolysis without renal failure was noted after suicidal ingestion of 29 tablets of Spalt N containing 7.25 g of acetaminophen, 7.25 g of phenazone and 1.45 g of caffeine by a 29 year-old weighing 73 kg. The maximum serum creatine kinase was 1920 U/L, serum myoglobins were 49 to 167 ng/mL. Acetaminophen, phenazone and caffeine were quantified and identified in serum by gas chromatography and gas chromatography/mass spectrometry. It is suggested that rhabdomyolysis might have been caused by caffeine.

Sensitive determination of piritramide in human plasma by gas chromatography.

A selective and sensitive method for the determination of piritramide in human plasma is described. A 1-ml aliquot of plasma was extracted with 10 ml of hexane-isoamyl alcohol (99.5:0.5, v/v) (extraction efficiency 86%) after addition of 50 microliters of 2 M ammonia and 20 microliters of aqueous strychnine solution (100 ng per 10 microliters) as internal standard. Gas chromatography was performed with J&W DB-1, 30 m x 0.53 mm I.D. separation column, film thickness 1.5 microns, using an nitrogen-phosphorus-sensitive detector. The assay was linear in the concentration range 3.75-2250 ng/ml (r = 0.999), with a lower limit of detection of 1-2 ng/ml. The precision was determined using spiked plasma samples (10 and 50 ng/ml), with coefficients of variation of 3.5 and 3.1% (intra-day; n = 5) and 4.6 and 4.1% (inter-day; n = 4). In the range 3.75-150 ng/ml, the accuracy of the assay was 3.36%. The method was used for the determination of piritramide plasma concentrations in patients receiving intra- or post-operative analgesia.

[Extreme duration of action of diazepam as a cause of respiratory insufficiency in a female geriatric patient]. / Extreme Wirkungsdauer von Diazepam als Ursache einer Ateminsuffizienz bei einer geriatrischen Patientin.

A 77-year-old woman who had undergone surgery of a non-malignant extracerebral retro-orbital tumor suffered postoperatively from respiratory failure due to impaired respiratory drive and unconsciousness of unknown origin and required artificial ventilation for 14 days. After cerebral and endocrinological causes had been excluded, the residual effects of diazepam were taken into consideration, since the patient had received this substance for premedication and during 3 days postoperatively (total 165 mg). After the application of flumazenil (Anexate), a specific benzodiazepine receptor antagonist, she awoke immediately and was extubated with sufficient spontaneous breathing. The hypothesis that diazepam was the causative agent for the respiratory failure and impaired consciousness was supported by the detection of high serum concentrations of diazepam and its active metabolite desmethyldiazepam. During the following 3 days repetitive injections of flumazenil were necessary to counteract recurring depression of respiration and vigilance. Thereafter further application of flumazenil was not necessary.

Acetonitrile serum concentrations and cyanide blood levels in a case of suicidal oral acetonitrile ingestion.

Acute acetonitrile toxicity is mainly dependent on the release of cyanide via hepatic metabolism. Although evaluated in animals, few data are available concerning the toxicokinetic parameters of acetonitrile and acetonitrile-liberated cyanide in human. This paper reports a case of suicidal oral acetonitrile ingestion of about 5 mL without severe symptoms of intoxication in a previously healthy adult male with a body weight of 60 kg. Acetonitrile serum concentrations as well as cyanide blood levels were determined over the whole hospitalization. The elimination half-lives calculated from these data were 32 h for acetonitrile and 15 h for cyanide. After sodium thiosulfate bolus application, the cyanide blood level rapidly decreased to 10% of the initial value, indicating that sodium thiosulfate sufficiently detoxifies acetonitrile-liberated cyanide. Since cyanide levels again increased to maximal values about 4.5 h after sodium thiosulfate application, continued thiosulfate therapy is required as predicted by the long elimination half-lives of acetonitrile and acetonitrile-liberated cyanide. Determination of cyanide and acetonitrile concentrations is recommended for the estimation of optimal individual sodium thiosulfate dosage.

Determination of 3'-azido-3'-deoxythymidine, 2',3'-dideoxycytidine, 3'-fluoro-3'-deoxythymidine and 2',3'-dideoxyinosine in biological samples by high-performance liquid chromatography.

A simple and fast high-performance liquid chromatographic assay for the determination of 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxycytidine (ddC), 3'-fluoro-3'-deoxythymidine (FT) and 2',3'-dideoxy-inosine (ddI) in complex biological matrices is described. The method allows rapid nucleoside determination using a phenyl column within extra- as well as intracellular media without further sample pretreatment and extraction procedures. The lower limit of detection is ca. 0.05 micrograms/ml for each nucleoside, and the separation can easily be optimized for AZT, ddC, FT and ddI by variation of the methanolic part of the mobile phase and the detector wavelengths.