Search

Das Spektrum der Behandlungsmöglichkeiten für genetisch bedingte Seltene Erkrankungen hat sich durch technologischen und wissenschaftlichen Fortschritt im Bereich der Gen- und Zelltherapeutika, sogenannter Arzneimittel für neuartige Therapien, wesentlich erweitert. Gentherapeutika zielen darauf ab, die genetische Grundursache der Erkrankung zu behandeln. Neben dem zurzeit noch vorrangigen Konzept der Genaddition, des Einbringens funktionsfähiger Genkopien in die Zielzellen über Genfähren, kann mit der neuen Methode der Genom-Editierung die krankmachende Mutation direkt im Erbgut des betroffenen Patienten korrigiert werden. In diesem Beitrag werden regulatorische Anforderungen an die klinische Evidenz bei Zulassung erläutert und anhand der Zulassung von zwei der fünfzehn seit 2018 in der Europäischen Union zugelassenen Gentherapeutika für Seltene Erkrankungen exemplarisch dargestellt. Am Beispiel der Gentherapeutika Libmeldy (Atidarsagen autotemcel) zur Behandlung von Patienten mit metachromatischer Leukodystrophie und Roctavian (Valoctocogen roxaparvovec) zur Behandlung von Patienten mit Hämophilie A werden Aspekte der Nutzen-Risiko-Bewertung in der Zulassung aufgezeigt. Besonderheiten in der Bewertung von einarmigen Studien mit kleinen Fallzahlen und Anforderungen im Hinblick auf die Isolierung und kausale Zuordnung des Behandlungseffekts werden diskutiert. Die Rolle von unter Alltagsbedingungen gewonnenen klinischen Daten (Real World Data) zur unterstützenden Wissensgenerierung vor und nach Zulassung wird kritisch beleuchtet. Die bedingte Zulassung wird im Hinblick auf das Inverkehrbringen von dringend benötigten Arzneimitteln und den Patientenzugang beleuchtet, und es werden Erfahrungen mit registerbasierten Daten im Hinblick auf regulatorische Anforderungen dargestellt.

Purpose: The purpose of this paper is to examine the relative financial strength and endurance of several paired classes of farmers according to business maturity (beginning versus mature farm businesses), farm operators’ age/experience (young versus older, more experienced farm operators), and farm size (small vs large farm businesses) by utilizing random-effects ordered logistic techniques. Design/methodology/approach: This study uses a credit migration approach to analyze the factors that impact the probability of farm credit migration rates. An ordered logit model is used to assess the influence that factors have on a farm upgrading, staying same, or downgrading in credit rating. Findings: Results show that increasing farm size will lead to a higher probability of class upgrades. Being a young farm operator, meanwhile, decreases this probability. Positive changes in money supply and farm real estate values were found to increase the likelihood of credit upgrades. Results also show trend reversal of credit risk movement, where upgrades (downgrades) are more likely to be followed by downgrades (upgrades). Originality/value: With farms being dependent on capital for growth, knowing what factors affect the ability of a farm to obtain credit lends insight in the agricultural credit markets. This paper is also the first to assess the impacts of these factors on small farms which constitute 92 percent of farms in the USA per the US Department of Agriculture.

Background: Risk stratification of elderly patients presenting with heart failure (HF) to an emergency department (ED) is an unmet challenge. We prospectively investigated the prognostic performance of different biomarkers in unselected older patients in the ED.Methods: We consecutively enrolled 302 non-surgical patients ?70 years presenting to the ED with a wide range of cardiovascular and non-cardiovascular comorbid conditions. N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1), ultrasensitive C-terminal pro-arginine-vasopressin (Copeptin-us) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of HF after reviewing all available baseline data using circulating NT-proBNP levels. A final diagnosis of HF was found in 120 (40%) of the 302 patients. All patients were followed up for cardiovascular death within the following 12 months. In order to test the prognostic performance of the investigated biomarkers we used boosting models with age and sex as mandatory covariates. Boosting is a statistical learning technique with built-in variable selection developed to obtain sparse and interpretable prediction models.Results: Follow-up was 100% complete. During a median follow-up time of 225 days (interquartile range (IQR) 156–319 days), 30 (9.9%) of 302 patients (aged 81±6 years) had cardiovascular deaths. Of these 30 patients, 21 had HF and nine had no HF diagnosed prior to admission. The boosting model selected MR-proADM and hs-cTNT as predictors of cardiovascular deaths. The median values of MR-proADM and hs-cTnT at presentation were significantly higher in patients with cardiovascular deaths compared to surviving patients during follow-up (2.56 nmol/L (IQR 1.62–4.48) vs. 1.11 nmol/L (IQR 0.83–1.80), P<0.001 and 81 ng/L (IQR 38–340) vs. 17 ng/L (IQR 0.9–38), P=0.004). One unit increase in the log-transformed MR-proADM levels was associated with a 1.99-fold risk of death (95% confidence interval (CI) 1.61–2.45, P<0.001). The second marker, hs-cTnT, showed an increased predicted risk but was not significantly correlated to event-free survival (hazard ratio 3.22, 95% CI 0.97–10.68, P=0.056).Conclusion: Within different biomarkers, MR-proADM was the only predictor of cardiovascular deaths in unselected older patients presenting to the ED.

Context.The detailed physical processes that lead to the formation of massive stars are still unknown. Observations that probe linear scales as small as $100\,$AU are necessary for improving our understanding in this area.

We report on interferometric observations at 3.2 and 1.3 mm of the massive young stellar object IRAS 20126+4104 obtained in the C34S and CH3OH lines and in the continuum emission. The C34S data confirm the existence of a Keplerian disk, as already suggested by various authors. However, the mass of the central object is ~7 $M_\odot$, significantly less than previous estimates. We believe that such a discrepancy is due to the fact that the rotation curve is affected not only by the star but also by the mass in the innermost regions of the disk itself: this leads to an overestimate of the stellar mass when low-density tracers are used to study the velocity field over regions larger than a few seconds of arc (i.e. a few 0.01 pc). On the basis of the line profiles we speculate that accretion onto the star might be still occurring through the disk. This seems consistent with current models of high-mass star formation which predict an accretion luminosity equal to that of IRAS 20126+4104 for a 7 $M_\odot$protostar. The CH3OH lines trace both the disk and the bipolar outflow previously detected in other molecules such as HCO+, SiO, and H2. New H2images obtained at 2.2 μm confirm that the outflow axis is undergoing precession. We elaborate a simple model that suitably fits the data thus allowing derivation of a few basic parameters of the precession.

We present high angular resolution observations obtained with the Owens Valley and the IRAM Plateau de Bure millimeter-wave interferometers toward the hot core in G29.96–0.02. We observed the ground state (6–5), (6–5), vibrationally excited ($v_8=1$) (6–5), and the (1–0) rotational transitions, as well as the 2.7 mm continuum emission. Our continuum maps show evidence of a compact source barely resolved whose diameter we estimate to be about 0.06 pc and whose emission mechanism is dominated by thermal emission from warm dust. Both the ground state and the $v_8=1$methyl cyanide lines, as well as other serendipituosly detected molecular transitions, arise from a compact source at the same position as the 2.7 mm continuum emission. The  observations sample the structure and kinematics of the molecular surroundings of the hot core and from the  data we estimate a gas mass of about $1.1 \times 10^3$$M_\odot$in a region with a diameter of 0.32 pc, corresponding to an average number density of about 106cm-3. Our data show evidence of both a temperature and density gradient in the hot core and its molecular surroundings. The density gradient, in particular, is consistent with the infalling scenario suggested by the presence of an East-West oriented velocity gradient, which is however of opposite sign in  and . We tentatively interpret the  velocity gradient as associated with infall, whereas the  gradient, consistent with that measured in  by Cesaroni et al. ([CITE]), is likely to trace a massive rotating disk.

Aim: Biomarkers can help to identity acute heart failure (AHF) as the cause of symptoms in patients presenting to the emergency department (ED). Older patients may prove a diagnostic challenge due to co-morbidities. Therefore we prospectively investigated the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) alone or in combination with other biomarkers for AHF upon admission at the ED.Methods: 302 non-surgical patients aged = 70 years were consecutively enrolled upon admission to the ED. In addition to NT-proBNP, mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-endothelin-1 (CT-proET-1) and ultra-sensitive C-terminal pro-vasopressin (Copeptin-us) were measured at admission. Two cardiologists independently adjudicated the final diagnosis of AHF after reviewing all available baseline data excluding the biomarkers. We assessed changes in C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) for the multimarker approach.Results: AHF was diagnosed in 120 (40%) patients (age 81±6 years, 64 men, 56 women). Adding MR-ADM to NT-proBNP levels improved C-index (0.84 versus 0.81; p=0.045), and yielded IDI (3.3%; p=0.002), NRI (17%, p<0.001) and continuous NRI (33.3%; p=0.002). Adding CT-proET-1 to NT-proBNP levels improved C index (0.86 versus 0.81, p=0.031), and yielded robust IDI (12.4%; p<0.001), NRI (31.3%, p<0.001) and continuous NRI (69.9%; p<0.001). No other dual or triple biomarker combination showed a significant improvement of both C-index and IDI.Conclusion: In older patients presenting to the ED, the addition of CT-proET-1 or MR-proADM to NT-proBNP improves diagnostic accuracy of AHF. Both dual biomarker approaches offer significant risk reclassification improvement over NT-proBNP.

Supplemental Digital Content is available in the text.

In this paper we present high resolution images and spectra toward 21 H2O maser sources in the vicinity of ultracompact (UC) HII regions. This survey provides the basis for future studies with milli–arcsecond resolution, utilizing very long baseline interferometry (VLBI) techniques. Emission from the $6_{16}-5_{23}$masing transition of interstellar H2O is observed in the close vicinity of UC HII regions with a median angular distance of $2\hbox{$.\!\!^{\prime\prime}$}9$and a median linear projected distance of $0.1\,$pc from the continuum peak. We find that for UC HII regions with cometary morphology the water maser emission is located in front of the cometary arc whereas for non-cometary UC HII regions the water masers are often observed projected onto the contours of the ionized gas. Due to the large median distance of the water masers from the I-front of the UC HII region, it is unlikely, that the water masers are formed in the shocked layer of warm molecular gas in the interface between the ionized gas of the UC HII region and surrounding molecular gas which is predicted by the Bow Shock theory of UC HII regions. A comparison with maps in the NH3inversion transitions shows that in at least 7 cases, the water masers are associated with hot (T$ > 100\,$K), dense (n(H${_2}) \approx 10^{7}\,$cm-3) molecular clumps. For the UC HII regions G5.89-0.38 and G45.07+0.13 we find spatial and velocity correspondence between water masers and outflowing molecular gas. It is thus likely, that for these sources the H2O masers are taking part in the bipolar outflow.

Hintergrund: Eine Krebsdiagnose und die nachfolgende Behandlung bedeuten für die meisten Betroffenen eine hohe psychische Belastung. Fragestellung:Ziel der vorliegenden Studie war es, die prädiktive Bedeutung von Achtsamkeit und Körperachtsamkeit für die Entwicklung von depressiven Symptomen nach einer Krebsdiagnose zu untersuchen. Methode:Die Studienteilnehmerinnen waren 51 Frauen mit erstdiagnostiziertem Mamma-Karzinom. Mittels hierarchischer Regressionsanalysen wurde untersucht, inwieweit das Ausmaß von selbstzugeschriebener Achtsamkeit und Körperachtsamkeit kurz nach der Diagnose den psychischen Zustand der Patientinnen im Krankheitsverlauf über acht Wochen vorhersagen kann. Die Variablen soziale Unterstützung und Religiosität wurden hierbei statistisch kontrolliert. Ergebnisse:Die soziale Unterstützung ermöglichte eine Prognose der selbstbeurteilten Depressivität im Krankheitsverlauf. Darüber hinaus hatte weder Achtsamkeit noch Körperachtsamkeit oder Religiosität einen Vorhersagewert. Schlussfolgerung:In der vorliegenden Studie konnte kein Hinweis darauf gefunden werden, dass Achtsamkeit oder Körperachtsamkeit bei der Krankheitsverarbeitung von relevanter Bedeutung sind. Mögliche methodische Gründe für diese Ergebnis werden diskutiert.

We discuss high angular resolution observations of ammonia toward four candidate high-mass starless cores (HMSCs). The cores were identified by the Balloon-borne Large Aperture Submillimeter Telescope (BLAST) during its 2005 survey of the Vulpecula region where 60 compact sources were detected simultaneously at 250, 350, and 500 mm. Four of these cores, with no IRAS-PSC or MSX counterparts, were mapped with the NRAO Very Large Array and observed with the Effelsberg 100 m telescope in the NH3(1,1) and (2,2) spectral lines. Our observations indicate that the four cores are cold (T k < 16 K) and show a filamentary and/or clumpy structure. They also show a significant velocity substructure within [?]1 km s-1. The four BLAST cores appear to be colder and more quiescent than other previously observed HMSC candidates, suggesting an earlier stage of evolution.

We present high angular resolution ($\theta _{\rm syn} \lesssim 0\rlap.{^{\prime \prime }}2$) observations of the 23.1 GHz methanol (CH3OH) transition toward the massive star-forming region NGC 7538 IRS 1. The two velocity components previously reported by Wilson et al. are resolved into distinct spatial features with brightness temperatures (TB ) greater than 104 K, proving their maser nature. Thus, NGC 7538 IRS 1 is the third region confirmed to show methanol maser emission at this frequency. The brighter 23.1 GHz spot coincides in position with a rare formaldehyde (H2CO) maser, and marginally with a 22.2 GHz water (H2O) maser, for which we report archival observations. The weaker CH3OH spot coincides with an H2O maser. The ratio of TB for the 23.1 GHz masers to that of the well-known 12.2 GHz CH3OH masers in this region roughly agrees with model predictions. However, the 23.1 GHz spots are offset in position from the CH3OH masers at other frequencies. This is difficult to interpret in terms of models that assume that all the masers arise from the same clumps, but it may result from turbulent conditions within the gas or rapid variations in the background radiation field.

We report high-sensitivity subarcsecond angular resolution observations of the massive star-forming region DR21(OH) at 3.6, 1.3, and 0.7 cm obtained with the Very Large Array. In addition, we conducted observations of CH3OH 44 GHz masers. We detected more than 30 new maser components in the DR21(OH) region. Most of the masers appear to trace a sequence of bow shocks in a bipolar outflow. The centimeter continuum observations reveal a cluster of radio sources; the strongest emission is found toward the molecular core MM1. The radio sources in MM1 are located about 5'' north of the symmetry center of the CH3OH outflow, and therefore they are unlikely to be associated with the outflow. Instead, the driving source of the outflow is likely located in the MM2 core. Although based on circumstantial evidence, the radio continuum from MM1 appears to trace free-free emission from shock-ionized gas in a jet. The orientation of the putative jet in MM1 is approximately parallel to the CH3OH outflow and almost perpendicular to the large-scale molecular filament that connects DR21 and DR21(OH). This suggests that the (accretion) disks associated with the outflows/jets in the DR21-DR21(OH) region have symmetry axes mostly perpendicular to the filament.

Aims:High-mobility group box protein 1 (HMGB1), a late-acting proinflammatory cytokine, is secreted actively by inflammatory cells, and released passively from necrotic cells. From the aspect that both inflammation and necrosis are involved in the pathogenesis in acute pancreatitis, the aim of the study was a joint investigation of the plasma concentrations of HMGB1, its soluble receptor for advanced glycation end-products (sRAGE), and the circulating DNA as a marker of cell death. Methods:62 patients with acute pancreatitis (30 mild, 32 severe), 20 patients with sepsis, and 20 healthy controls were enrolled in the study. HMGB1 and sRAGE plasma levels were measured by means of ELISA. Plasma DNA concentrations were estimated by real-time quantitative PCR for the ß-globin gene. Results:The circulating HMGB1 level was significantly higher in patients with severe acute pancreatitis (13.33 ± 2.11 ng/ml) than in healthy controls (0.161 ± 0.03 ng/ml) or than in patients with mild pancreatitis (2.64 ± 0.185 ng/ml). The plasma concentration of sRAGE was highest in patients with sepsis (2,210 ± 252 pg/ml), while the levels of sRAGE correlated inversely with that of HMGB1 in patients with acute pancreatitis. The plasma DNA level was significantly elevated in patients with severe acute pancreatitis (2,206 ± 452 ng/ml). Conclusion:A complex study of the plasma levels of HMGB1, sRAGE and circulating DNA can be informative in evaluations of acute pancreatitis with different levels of severity.

AbstractAims:High-mobility group box protein 1 (HMGB1), a late-acting proinflammatory cytokine, is secreted actively by inflammatory cells, and released passively from necrotic cells. From the aspect that both inflammation and necrosis are involved in the pathogenesis in acute pancreatitis, the aim of the study was a joint investigation of the plasma concentrations of HMGB1, its soluble receptor for advanced glycation end-products (sRAGE), and the circulating DNA as a marker of cell death. Methods:62 patients with acute pancreatitis (30 mild, 32 severe), 20 patients with sepsis, and 20 healthy controls were enrolled in the study. HMGB1 and sRAGE plasma levels were measured by means of ELISA. Plasma DNA concentrations were estimated by real-time quantitative PCR for the β-globin gene. Results:The circulating HMGB1 level was significantly higher in patients with severe acute pancreatitis (13.33 ± 2.11 ng/ml) than in healthy controls (0.161 ± 0.03 ng/ml) or than in patients with mild pancreatitis (2.64 ± 0.185 ng/ml). The plasma concentration of sRAGE was highest in patients with sepsis (2,210 ± 252 pg/ml), while the levels of sRAGE correlated inversely with that of HMGB1 in patients with acute pancreatitis. The plasma DNA level was significantly elevated in patients with severe acute pancreatitis (2,206 ± 452 ng/ml). Conclusion:A complex study of the plasma levels of HMGB1, sRAGE and circulating DNA can be informative in evaluations of acute pancreatitis with different levels of severity.Copyright © 2009 S. Karger AG, Basel and IAP

Recent controlled studies that evaluated the efficacy of an adjuvant antithrombin (AT) III therapy in severe sepsis used a uniform AT-III dose and duration of therapy and did not adjust to the actual AT-III deficit. It was the aim of the present study to explore if surgical patients with severe sepsis might have a treatment benefit from an activity-guided AT-III therapy. We performed a retrospective cohort analysis using an intensive care unit (ICU) database. To examine the effect of AT-III on outcome and on red cell transfusion rate, multivariate generalized additive models (GAMs), Cox-type additive hazard regression models, and propensity score adjustments were used. Five hundred forty-five postoperative surgical patients requiring ICU therapy because of severe sepsis were analyzed. Antithrombin III was given to those patients believed to be at a high risk of dying. Antithrombin III therapy was guided by the individual AT-III activity and aimed at the maintenance of an activity of at least 100%. Antithrombin III supplementation was discontinued after the plasma AT-III activity had been persistently normal without simultaneous AT-III infusion. We found that patients receiving additional AT-III (n = 230) were sicker than those on standard therapy (n = 315; admission Acute physiology and chronic health evaluation II score, 19.8 ± 7.3 vs. 17.9 ± 7.1 mean ± SD; P< 0.005). Correspondingly, 28-day mortality was higher in patients who had an additional AT-III therapy than in those on standard therapy (46.3% vs. 36.9%; P< 0.03), as was the number of red cell units transfused during ICU stay (21.5 ± 26.7 vs. 9.3 ± 12.1; P< 0.001). At multivariate analysis, there was no significant effect of AT-III therapy on 28-day mortality (GAM odds ratio, 1.012; 95% confidence interval CI, 0.651 - 1.573; P= 0.957) and 90-day survival time (Cox-type additive hazard regression hazard ratio, 1.034; 95% CI, 0.779 - 1.387; P= 0.794). However, AT-III therapy was associated with a significantly higher frequency of red cell unit transfusion (GAM/zero-inflated Poisson estimate, 1.26; 95% CI, 1.15 - 139; P< 0.001). Our results suggest that there seems to be no relevant effect of an activity-guided AT-III therapy on the prognosis of surgical patients with severe sepsis. However, transfusion frequency rises by AT-III therapy.

VLA observations of large-scale H I and OH absorption in the merging galaxy of NGC 6240 are presented with 1'' resolution. H I absorption is found across large areas of the extended radio continuum structure with a strong concentration toward the double nucleus. The OH absorption is confined to the nuclear region. The H I and OH observations identify fractions of the gas disks of the two galaxies and confirm the presence of central gas accumulation between the nuclei. The data clearly identify the nucleus of the southern galaxy as the origin of the symmetric superwind outflow and also reveal blueshifted components resulting from a nuclear starburst. Various absorption components are associated with large-scale dynamics of the system including a foreground dust lane crossing the radio structure in the northwest region.

The nearby starburst galaxy NGC 253 was mapped in the ammonia $(J, K) = (1, 1), (2, 2)$, and $(3, 3)$lines in the 23 GHz region with the Very Large Array. The angular resolutions were about $4 {{}^{\prime \prime }} \times 3 {{}^{\prime \prime }}$. The distributions of the three lines were different from one another. The $(1, 1)$and $(3, 3)$lines were distributed along the bar mainly at the northeastern and southwestern regions from the center, but the $(2, 2)$line is distributed mainly at two clumps in the southwestern region from the center. In addition, the $(1, 1)$line showed absorption at the central region. The obtained rotational temperatures were $<15 \hbox{--} 28 \,\mathrm{K}$(lower limit), depending on the clumps. The ammonia distributions are generally consistent with estimates from our single-dish results already published. The distributions of ammonia were compared with those of continuum and several other molecular lines.

OBJECTIVE: To collect data on the consultation frequency and demographic profile of victims of violence attending an emergency department (ED) in Switzerland. METHODS: We undertook screening of all admitted adult patients (>16 years) in the ED of the CHUV, Lausanne, Switzerland, over a 1 month period, using a modified version of the Partner Violence Screen questionnaire. Exclusionary criteria were: life threatening injury (National Advisory Committee on Aeronautics score 4), or inability to understand or speak French, to give oral informed consent, or to be questioned without a family member or accompanying person being present. Data were collected on history of physical and/or psychological violence during the previous 12 months, the type of violence experienced by the patient, and if violence was the reason for the current consultation. Sociodemographic data were obtained from the registration documents. RESULTS: The final sample consisted of 1602 patients (participation rate of 77.2%), with a refusal rate of 1.1%. Violence during the past 12 months was reported by 11.4% of patients. Of the total sample, 25% stated that violence was the reason for the current consultation; of these, 95% of patients were confirmed as victims of violence by the ED physicians. Patients reporting violence were more likely to be young and separated from their partner. Men were more likely to be victims of public violence and women more commonly victims of domestic violence. CONCLUSIONS: Based on this monthly prevalence rate, we estimate that over 3000 adults affected by violence consult our ED per annum. This underlines the importance of the problem and the need to address it. Health services organisations should establish measures to improve quality of care for victims. Guidelines and educational programmes for nurses and physicians should be developed in order to enhance providers’ skills and basic knowledge of all types of violence, how to recognise and interact appropriately with victims, and where to refer these patients for follow up care in their local networks.

We report the results of the presently lowest frequency spectral line survey of the asymptotic giant branch carbon star IRC +10deg216. The entire Arecibo C band (4-6 GHz) was observed with a noise level of ~0.3 mJy (1 s). We report the detection of HC5N (J = 2-1), which is the lowest frequency transition of the HC5N molecule found in the envelope of IRC +10deg216. The HC5N J = 2 column density derived from our observations confirms the presence of two temperature components in the molecular envelope of IRC +10deg216. The HC5N J = 2-1 transition traces the cold molecular component characterized by an excitation temperature of ~13.8 K. We derive upper limits for several transitions of molecules that had previously been detected in IRC +10deg216 at higher frequencies. We also report the frequency ranges in the Arecibo C band that were affected by radio frequency interference.

BackgroundImmediate and long-term results after balloon dilatation of pulmonary valve stenosis in our unit. Methods and patientsAll 111 patients (1 day–18 years) who have had balloon dilatation of a pulmonary valvar stenosis between 12/1987 and 8/1997 were divided into 4 groups: Typical valvar pulmonary stenosis (group A; n=78), stenosis with dysplastic pulmonary valve (group B; n=10), critical pulmonary stenosis (group C; n=16) and pulmonary atresia after transcatheter or operative opening of the valve (group D; n=7). Patients with pulmonary stenosis and complex congenital heart disease were excluded. ResultsThe average systolic transvalvular gradient was reduced from 68.5 to 27.2mmHg (60%) immediately after balloon dilatation. After a follow up of 48.8±37 months 101 patients could be reevaluated. In group A (n=69 at FU) and C (n=16 at FU) 81% showed a systolic transvalvular gradient <30mmHg after one and 83% (A) respective 94% (C) after two balloon dilatations. In group B (n=9 at FU) 44% exhibited a systolic gradient <30mmHg after one and 56% after two balloon dilatations. In group D (n=7 at FU) 57% showed a systolic gradient <30mmHg with no further improvement by a second dilatation. Over all, 80% of our patients could be treated sufficiently by transcatheter means. The rate of major complications was 7.3% with no lasting residuals at follow up and no deaths. ConclusionBalloon dilatation of the pulmonary valve is secure and effective. Best results are obtained in patients with typical pulmonary valve stenosis and in newborns and infants with critical pulmonary valve stenosis. FragestellungUnmittelbare Ergebnisse und Langzeitverlauf nach Ballondilatation einer Pulmonalklappenstenose in unserer Klinik. Methode und PatientenAlle 111 Patienten (1 Tag bis 18 Jahre), die sich zwischen 12/1987 und 8/1997 einer Ballondilatation der Pulmonalklappe unterzogen, wurden in 4 Gruppen eingeteilt: Typische valvuläre Pulmonalstenose (Gruppe A; n=78), dysplastische Pulmonalklappe mit Stenose (Gruppe B; n=10), kritische Pulmonalklappenstenose (Gruppe C; n=16) und Pulmonalklappenatresie nach interventioneller oder operativer Eröffnung der Klappe (Gruppe D; n=7). Patienten mit Pulmonalstenose in Verbindung mit einem komplexen Herzfehler wurden ausgeschlossen. ErgebnisseDer mittlere systolische transvalvuläre Gradient wurde von 68,5 auf 27,2mmHg (60%) unmittelbar nach der Dilatation reduziert. Nach einer Nachbeobachtungszeit von 48,8±37 Monaten wurden 101 Patienten nachuntersucht. In Gruppe A (n=69 bei NU) und C (n=16 bei NU) zeigten je 81% einen systolischen transvalvulären Gradienten unter 30mmHg nach einer und 83% (A) bzw. 94% (C) nach zwei Ballondilatationen. In Gruppe B (n=9 bei NU) wiesen 44% einen systolischen Gradienten unter 30mmHg nach einer und 56% nach zwei Ballondilatationen auf. In Gruppe D (n=7 bei NU) zeigten 57% einen systolischen Gradienten unter 30mmHg, ohne weitere Verbesserung durch eine 2. Dilatation. Insgesamt konnten 80% unserer Patienten ausreichend durch interventionelle Maßnahmen behandelt werden. Die Rate an ernsten Komplikationen lag bei 7,3%, die alle bei der Nachuntersuchung keine dauerhaften Schäden hinterlassen hatten. Es traten keine Todesfälle auf. SchlussfolgerungDie Ballondilatation der Pulmonalklappe ist sicher und effektiv. Die besten Ergebnisse werden bei Patienten mit typischer valvulärer Pulmonalstenose und bei Neugeborenen und Säuglingen mit kritischer Pulmonalstenose erreicht.

Here we discuss the effects of large ambient pressures and decreasing density gradients on the observed properties of dusty UC hii regions. Dust absorption can effectively reduce the size of the photo ionized region, and density gradients can modify the spectral index of the emission. The effects of the density gradients seem to be present in both galactic and extragalactic HII regions.

We have observed the G9.62+0.19 region of massive star formation with the IRAM 30 m single-dish telescope in the HCO+(1-0), SO(43-32), and SiO(5-4) spectral lines, and with the IRAM Plateau de Bure interferometer in the 3 mm continuum and the HCO+(1-0) and CH3OH(153-144) A-spectral lines. We detect a high-velocity molecular ouflow with a total velocity extent of at least 60 km s-1. The orientation of the outflow axis is very close to the line of sight. Our estimates of the mass and energetics of the outflowing gas indicate that a massive object must be responsible for driving the flow, with the hot core region G9.62+0.19 F as the most likely candidate. We also detect emission from hot methanol coincident with the position of continuum component E, but CH3OH(153-144) A-is not detected at the position of the G9.62+0.19 F hot core region.

One of the major problems of children with severe congenital heart disease (CHD) is their poor nutritional status. Among other consequences, it influences the surgical outcome. Retrospectively we present our experience with percutaneous endoscopic gastrostomy (PEG) in 15 children with CHD. This technique allows enteral nutritional support without the disadvantages related to long-term nasogastric tube feeding. Major complications were absent, and minor complications were rare both at PEG insertion, which was performed under deep sedation, and during feeding via PEG tube. In 4 of the 8 children who were followed for at least 6 months the age-matched body weight increased more than one standard deviation. In 2 other patients it increased more than 0.5 standard deviations. In 7 children the tube was removed after 2.5 to 42 months since enteral support was no longer necessary. Apart from initial reservations the parental acceptance of PEG was good. We conclude that the PEG is a safe and reliable technique to support enteral nutrition in children with severe CHD.

Here we review some recent results on the observed properties of UCH IIregions, and on the new class of Super-ultra-compact H IIregions, and describe the theoretical scheme for H IIregion expansion, from star-forming cloud cores to the more diffuse external medium. High-pressure cores can stop the expansion on relatively short time scales, of the order of 3× 104yr, and the resulting pressure equilibrium UCH IIregions have small sizes and large ion densities. If the ionization front enters into the decreasing density gradient of the cloud core, the expansion is accelerated and the H IIregion“pops” out of the core and becomes a “blister”-like region. The properties of the outflows depend on the cloud density structure, and a variety of different shocks can be formed. Density inhomogeneities inside photoionized regions are smoothed out on short time scales, but new clumps are continuously created at the cool shell generated by the shock front. Instabilities in both the ionization and shock fronts cause the fragmentation of the shell, maintaining the presence of clumps during the whole evolution.

We have observed 16 regions of massive star formation in the J= 1-0, 2-1 rotational transitions of C17O and the J= 2-1 transition of C18O with the IRAM 30 m telescope. We have also observed the J= 2-1, 3-2 rotational transitions of C17O with the KOSMA 3 m telescope. The C17O-emitting clumps typically have sizes of 1 pc and average densities and temperatures of 105cm-3and 25 K, respectively. Clump masses from 103to 4 × 104M?are found, and most of the clumps are virialized in the sense that their gravitational energy is of the same order as bulk kinetic energy inferred from the line width. We also compare the derived masses with values obtained using measurements of the millimeter/submillimeter dust continuum emission and find that the dust continuum masses tend to be higher by about a factor of 2. We estimate the masses of early-type stars (more massive than 15 M?) embedded in the sources of our sample and conclude that the ratio of "O-star mass" to gas mass is roughly 1% in most cases.

We present observations of the 1.3 cm continuum and NH3(2,2) and (4,4) inversion lines toward the two ultracompact H II regions G45.12+0.13 and G45.47+0.05 with a resolution of about 3''. In G45.12+0.13 we find that the continuum emission from the ultracompact core is embedded in a larger region with an extent of about 20''x10''. Compact absorption in the NH3(2,2) and (4,4) lines is detected against the bright continuum core. The ammonia data indicate Trot=78 K and N(NH3)=1.4x1016 cm[?]2. The molecular gas traced by the NH3 absorption is blueshifted by about 5 km s[?]1 with respect to the ionized gas and the bulk of the molecular gas in the region. Possibly the ammonia absorption traces the molecular gas at the base of an outflow which originates very close to the ultracompact H II region. In the case of G45.47+0.05, we measure a deconvolved size of 1.''5x0.''8 for the region of 1.3 cm continuum emission. We detect extended emission in the NH3(2,2) line in the vicinity of the ionized gas. Compact absorption is detected in both the (2,2) and (4,4) line against the 1.3 cm continuum. The absorption line data indicate Trot=59 K and N(NH3)=1.8x1017 cm[?]2. The ammonia absorption occurs at a velocity redshifted by about 3.5 km s[?]1 with respect to the emission. This supports the hypothesis of a remnant infalling molecular core onto the ultracompact H II region.

We have conducted a 3.6 cm radio-continuum survey with the VLA in its compact D-array to look for extended radio-continuum emission around known ultracompact H II regions. We find extended emission in 12 out of 15 fields. The extended emission ranges in size up to 5', with typical diameters of 60'', or 2 pc. In some cases, the extended component produces an order of magnitude more flux than the ultracompact component. It is possible that the extended emission is from H II regions not connected with the ultracompact H II regions, but on the basis of the morphology of the emission, we believe that it is possible or even likely that the ultracompact and extended emission are directly connected in about half of the sources. The possible consequences of directly connected extended emission are profound. We may be forced to reconsider the definition of an ultracompact H II region and consider models in which dense, ultracompact ionized components are embedded in less dense, more extended regions.

Background: Neonatal alloimmune thrombocytopenia (NAIT) is in most cases due to pregnant women with HPA-1b platelet phenotype producing antibodies to HPA-1a platelets of the fetus, which may lead to intracranial haemorrhage with subsequent death or lifelong morbidity. The availability of sensitive, reliable, straightforward, and inexpensive assays would enable large-scale screening in pregnancy and may help avoid NAIT. Methods: A recently developed enzyme-linked immunosorbent assay (ELISA) was produced in kit form incorporating modified reagents and enabling distribution to 21 international Platelet Immunology and Blood Centres (see Acknowledgments). The kits were assessed using anticoagulated whole-blood samples stored up to 10 weeks at 4°C. Each centre tested its own blood samples most of which had been previously typed by established assays. Results: Of the 152 samples that were tested, all 31 HPA-1b phenotypes were correctly identified by the kit. The respective mean ± standard deviation of the specific absorbances of HPA-1b and HPA-1a samples were: 0.52±0.15 and 0.12±0.06 (p&lt;0.0005). In addition, the modified ELISA showed 100% concordance with PCR-SSP in the phenotyping of 93 donors. Finally, a comparison between freshly prepared and stored kits showed that the kit was stable for at least 2 years at 4°C. Conclusions: The international trial showed that the modified whole-blood ELISA kit is very well suited for wide-scale screening in pregnancy. Moreover, the ELISA kit could be used for large-scale phenotyping of blood donors, with HPA-1b-typed individuals getting invited to become apheresis platelet donors for patients with NAIT.

Factors inducing Fe-chlorosis in grape vines had been studied during a 2 years field review.Based on soil and leaf samples, taken consecutively every two weeks over the whole vegetation period, the variable parameters were determined. The comparison was achieved between chlorotic and nonchlorotic stands of grape vines, differing in rootstocks but grafted with the same cultivar.By means of different statistical methods, the influence of the sole parameters were tested.Chlorosis in its different intensities was'neither induced by an absolut Fe-deficiency (in leaf or soil) nor by a relative Fe-deficiency in the soil, as shown by the amounts of DTPA-extractable Fe.In spite of this fact, the concentration of water and citrate buffer-extractable Fe in leaves was in most cases lower, while the 0,5 n HCl- and 1,0 n HCl-extractable Fe was higher in chlorotic leaves compared with green ones.All of the applied statistical methods proved in accordance the important influence of water soluble phosphate in the soil layer between 20 and 60 cm. The comparison with additional results from field surveys primarily points to a complex acting through HCO3- -Pw on and energy status during the development of the physiologically induced iron-chlorosis.

In pot experiments the influence of bicarbonate and phosphate on the upset of chlorosis in grapevine grafted on two rootstocks with different Fe-efficiency was studied. Grapevine grafted with the susceptible rootstock showed severe symptoms of chlorosis in the bicarbonate trials, while those on Fe-efficient rootstock remained green during the whole experiment. Bicarbonate reduced the iron concentration in both the leaves and stems of the susceptible plants, but not in the resistent ones.The accumulation of iron at the root surface in these trials were more pronounced in the susceptible than in the non-susceptible rootstocks.The pH of the cytoplasm from chlorotic leaves was higher than from the green ones.The main effect of bicarbonate on the Fe-nutrition of grapevine is believed to be due to an alkalinisation of the rhizosphere and the cytoplasm as well as, disturbing the enzymatic Fe-reduction process.

In field experiments on three different locations it was looked for indicators inducing iron chlorosis on grape-vines grafted on two rootstocks: Couderc 3309 (susceptible) and Kober 5 BB (resistant). Investigating the soil it was found that the bicarbonate concentration in the rooted soil depth (20-60 cm) did not differ between chlorotic plants and the green ones, whereas the phosphate concentration under chlorotic plants is significantly higher. There exists no differences in the iron content of the soil.Calculating stepwise regression functions it was possible to discriminate between chlorotic and healthy plants. Under chlorotic plants bicarbonate effects the iron availability to 30% for resistant, and up to 52% for the susceptible rootstocks.Analyzing green and chlorotic leaves it could be shown that Ca and K content is significantly higher in chlorotic ones. Typical is also the significant increase in total iron content.

Purpose: We document changes in pressure-flow study parameters in patients treated by transurethral microwave thermotherapy. Materials and Methods: Pressure-flow study tracings before and after therapy from 75 patients with benign prostatic hyperplasia were analyzed. Patients were stratified according to the predominant type of obstruction at screening (constrictive or obstructive). Results: An improvement in Madsen score and flow rates was noted at 6 months in both groups. In contrast to compressive obstruction patients, however, those with constrictive obstruction also showed significant changes in pressure-flow study parameters, including detrusor pressure at maximum flow, maximum flow rate and urethral resistance factor. Conclusions: Patients with predominantly constrictive obstruction are the best candidates for microwave thermotherapy.

Purpose: We evaluated the urodynamic changes after high energy microwave thermotherapy in patients with lower urinary tract symptoms and benign prostatic enlargement. Materials and Methods: A total of 120 patients was available for analysis with urodynamic investigation and pressure-flow studies before and 6 months after treatment. Several obstruction parameters were used to evaluate treatment outcome. Results: A significant decrease (p less than 0.001) in all obstruction parameters was noted. Mean detrusor pressure at maximum flow decreased from 64.7 to 39.1 cm. water, urethral resistance factor from 41.8 to 23.5 cm. water and linear passive urethral resistance relation from 3.0 to 1.4. Analysis of subgroups showed better results in patients with greater degrees of obstruction. Conclusions: High energy thermotherapy results in a significant and substantial decrease in bladder outlet obstruction.

We investigated the international differences in the reporting of lower urinary tract symptoms and related bother in patients with symptoms suggestive of bladder outlet obstruction.

We attempted to identify any parameter that could possibly lead to a successful treatment outcome after transurethral microwave thermotherapy.

During recent years, thousands of patients with benign prostatic hyperplasia worldwide have been treated with transurethral microwave thermotherapy and various laser techniques. Last year's publications show developments in both technologies which define increasingly their indications with regard to clinical efficiency and morbidity. According to preliminary data published on high-energy transurethral microwave thermotherapy 2.5, as thermotherapy progresses towards thermoablation there is increased morbidity. Papers concerning laser treatment show the first long-term data comparing the latter with transurethral resection of the prostate, the studies being carried out over a period of 3 years. Results comparing visual laser ablation of the prostate with laser or electrovaporization have also been described, as well as increasing modification of surgical technique by combinations of various methods.

We documented the results of high energy transurethral microwave thermotherapy in the treatment of benign prostatic hyperplasia.