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International audience; High-impedance surfaces (HIS) are investigated here for the above-IC integration of sub-millimeter-wave (350 µm here) detectors on CMOS electronics using standard thin film manufacturing processes and materials. We demonstrate theoretically and experimentally the efficient optical absorption of a resistive dipole array above an HIS at cryogenic temperature. More specifically, an absorption above 78% in linear polarization is obtained over a bandwidth of 100 µm around a center wavelength of 350 µm. These results confirm the promising performances of HIS structures in the perspective of future polarimetric bolometers in terms of absorption efficiency, bandwidth and cross-polarization discrimination.

Current flow in electronic devices can be asymmetric with bias direction, a phenomenon underlying the utility of diodes1 and known as non-reciprocal charge transport2. The promise of dissipationless electronics has recently stimulated the quest for superconducting diodes, and non-reciprocal superconducting devices have been realized in various non-centrosymmetric systems3–10. Here we investigate the ultimate limits of miniaturization by creating atomic-scale Pb–Pb Josephson junctions in a scanning tunnelling microscope. Pristine junctions stabilized by a single Pb atom exhibit hysteretic behaviour, confirming the high quality of the junctions, but no asymmetry between the bias directions. Non-reciprocal supercurrents emerge when inserting a single magnetic atom into the junction, with the preferred direction depending on the atomic species. Aided by theoretical modelling, we trace the non-reciprocity to quasiparticle currents flowing by means of electron–hole asymmetric Yu–Shiba–Rusinov states inside the superconducting energy gap and identify a new mechanism for diode behaviour in Josephson junctions. Our results open new avenues for creating atomic-scale Josephson diodes and tuning their properties through single-atom manipulation.

Contains fulltext : 249977.pdf (Publisher’s version ) (Closed access) BACKGROUND: It is important to evaluate whether a new treatment for heart failure with reduced ejection fraction (HFrEF) provides additive benefit to background foundational treatments. As such, we aimed to evaluate the efficacy and safety of empagliflozin in patients with HFrEF in addition to baseline treatment with specific doses and combinations of disease-modifying therapies. METHODS: We performed a post-hoc analysis of the EMPEROR-Reduced randomised, double-blind, parallel-group trial, which took place in 520 centres (hospitals and medical clinics) in 20 countries in Asia, Australia, Europe, North America, and South America. Patients with New York Heart Association (NYHA) classification II-IV with an ejection fraction of 40% or less were randomly assigned (1:1) to receive the addition of either oral empagliflozin 10 mg per day or placebo to background therapy. The primary composite outcome was cardiovascular death and heart failure hospitalisation; the secondary outcome was total heart failure hospital admissions. An extended composite outcome consisted of inpatient and outpatient HFrEF events was also evaluated. Outcomes were analysed according to background use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs) or angiotensin receptor neprilysin inhibitors (ARNIs), as well as β blockers and mineralocorticoid receptor antagonists (MRAs) at less than 50% or 50% or more of target doses and in various combinations. This study is registered with ClinicalTrials.gov, NCT03057977. FINDINGS: In this post-hoc analysis of 3730 patients (mean age 66·8 years [SD 11·0], 893 [23·9%] women; 1863 [49·9%] in the empagliflozin group, 1867 [50·1%] in the placebo group) assessed between March 6, 2017, and May 28, 2020, empagliflozin reduced the risk of the primary outcome (361 in 1863 participants in the empagliflozin group and 462 of 1867 in the placebo group; HR 0·75 [95% CI 0·65-0·86]) regardless of background therapy or its target doses for ACE inhibitors or ARBs at doses of less than 50% of the target dose (HR 0·85 [0·69-1·06]) and for doses of 50% or more of the target dose (HR 0·67 [0·52-0·88]; p(interaction)=0·18). A similar result was seen for β blockers at doses of less than 50% of the target dose (HR 0·66 [0·54-0·80]) and for doses of 50% or more of the target dose (HR 0·81 [0·66-1·00]; p(interaction)=0·15). Empagliflozin also reduced the risk of the primary outcome irrespective of background use of triple therapy with an ACE inhibitor, ARB, or ARNI plus β blocker plus MRA (given combination HR 0·73 [0·61-0·88]; not given combination HR 0·76 [0·62-0·94]; p(interaction)=0·77). Similar patterns of benefit were observed for the secondary and extended composite outcomes. Empagliflozin was well tolerated and rates of hypotension, symptomatic hypotension, and hyperkalaemia were similar across all subgroups. INTERPRETATION: Empagliflozin reduced serious heart failure outcomes across doses and combinations of disease-modifying therapies for HFrEF. Clinically, these data suggest that empagliflozin might be considered as a foundational therapy in patients with HFrEF regardless of their existing background therapy. FUNDING: Boehringer Ingelheim and Eli Lilly and Company.

When electrons populate a flat band their kinetic energy becomes negligible, forcing them to organize in exotic many-body states to minimize their Coulomb energy. The zeroth Landau level of graphene under magnetic field is a particularly interesting strongly interacting flat band because inter-electron interactions are predicted to induce a rich variety of broken-symmetry states with distinct topological and lattice-scale orders. Evidence for these stems mostly from indirect transport experiments that suggest that broken-symmetry states are tunable by boosting the Zeeman energy or by dielectric screening of the Coulomb interaction. However, confirming the existence of these ground states requires a direct visualization of their lattice-scale orders. Here, we image three distinct broken-symmetry phases in graphene using scanning tunneling spectroscopy. We explore the phase diagram by tuning the screening of the Coulomb interaction by a low or high dielectric constant environment, and with a magnetic field. In the unscreened case, we unveil a Kekul\'e bond order, consistent with observations of an insulating state undergoing a magnetic-field driven Kosterlitz-Thouless transition. Under dielectric screening, a sublattice-unpolarized ground state emerges at low magnetic fields, and transits to a charge-density-wave order with partial sublattice polarization at higher magnetic fields. The Kekul\'e and charge-density-wave orders furthermore coexist with additional, secondary lattice-scale orders that enrich the phase diagram beyond current theory predictions. This screening-induced tunability of broken-symmetry orders may prove valuable to uncover correlated phases of matter in other quantum materials., Comment: Main text + SI

Graphene's original promise to succeed silicon faltered due to pervasive edge disorder in lithographically patterned deposited graphene and the lack of a new electronics paradigm. Here we demonstrate that the annealed edges in conventionally patterned graphene epitaxially grown on a silicon carbide substrate (epigraphene) are stabilized by the substrate and support a protected edge state. The edge state has a mean free path that is greater than 50 microns, 5000 times greater that the bulk states and involves a theoretically unexpected Majorana-like zero-energy non-degenerate quasiparticle that does not produce a Hall voltage. In seamless integrated structures, the edge state forms a zero-energy one-dimensional ballistic network with essentially dissipationless nodes at ribbon-ribbon junctions. Seamless device structures offer a variety of switching possibilities including quantum coherent devices at low temperatures. This makes epigraphene a technologically viable graphene nanoelectronics platform that has the potential to succeed silicon nanoelectronics., File contains article and supplementary. Nature Communications (in print)

Topological Josephson junctions designed on the surface of a 3D-topological insulator (TI) harbor Majorana bound states (MBS's) among a continuum of conventional Andreev bound states. The distinct feature of these MBS's lies in the $4\pi$-periodicity of their energy-phase relation that yields a fractional ac Josephson effect and a suppression of odd Shapiro steps under $r\!f$ irradiation. Yet, recent experiments showed that a few, or only the first, odd Shapiro steps are missing, casting doubts on the interpretation. Here, we show that Josephson junctions tailored on the large bandgap 3D TI Bi$_2$Se$_3$ exhibit a fractional ac Josephson effect acting on the first Shapiro step only. With a modified resistively shunted junction model, we demonstrate that the resilience of higher order odd Shapiro steps can be accounted for by thermal poisoning driven by Joule overheating. Furthermore, we uncover a residual supercurrent at the nodes between Shapiro lobes, which provides a direct and novel signature of the current carried by the MBS. Our findings showcase the crucial role of thermal effects in topological Josephson junctions and lend support to the Majorana origin of the partial suppression of odd Shapiro steps., Comment: Revised article and Supplemental material

Endoscopic subureteral injection of bulking agents has become a widespread treatment for vesicoureteral reflux (VUR) in children. Various biological and plastic materials have been introduced for this purpose with different success and complication rates. Evaluations of this method in previous studies have focused on the success rate of eliminating VUR, whereas complications have been less frequently reported in detail. This report describes four children with VUR grade I to IV-V who experienced severe complications after endoscopic treatment with polydimethylsiloxane at the age of 5 months to 7 years. Three children developed urosepsis and two patients obstructive acute renal failure. These complications required repeated hospitalizations with extensive diagnostic and therapeutic procedures. Percutaneous nephrostomy was necessary in three patients and ureteroneocystostomy was eventually performed in all. These observations suggest that endoscopic treatment of VUR in childhood with polydimethylsiloxane can lead to severe postoperative complications and that a standardized follow-up should be an integral part of endoscopic procedures.

Worldwide, specific pediatric allocation schemes successfully try to minimize waiting time for children with end-stage renal disease (ESRD). The article is a review of current issues in pediatric kidney transplantation. The procedure is the treatment of choice for children and adolescents with ESRD, with 1- and 3-year graft survival rates of 95% and 90% and recipient survival after 5 and 10 years of 95% and 90%. Preoperative surgery is often necessary to minimize negative effects of congenital anomalies. No minimum age exists for pediatric transplantation, but most often the recipient body weight is ideally above 10 to 15 kg. Technical concepts should include extravesical anastomosis, stenting of the ureter, and potentially intraperitoneal placement of the graft. Immunosuppression has constantly improved. The aim is a tailored regimen to reduce side effects and improve compliance, which necessitates intense counseling of the child and the parents prior to, during, and after transplantation as many adolescents lose their graft due to noncompliance. Intense follow-up must also exclude infections, especially with herpes and polyoma viruses. For the future, age matching may be only one promising concept to improve results. As only a small number of children require the procedure in each country, multinational studies should be initiated to optimize outcomes in children and adolescents.

BACKGROUND: Within evidence-based practice in occupational therapy a hierarchy of external evidence methods is built up in order to assess the validity degree concerning practical problems. Occupational therapy research uses methods and approaches of clinical experimental research, (quantitative) health care research and qualitative research. Particularly methods of health care and qualitative research are more likely classified in lower ranks of the classical evidence hierarchy although their validity degree might be high depending on the way of problem posing. OBJECTIVE: In this respect the question arises what a model considering the external evidence of decision making should look like which takes into account the 3 research levels to the same extent and measures up to the hierarchy model. METHOD/RESULTS: The justifications of the 3 research levels’ validity, their pros and cons as well as their classification in classical evidence hierarchy are illustrated. Based on these considerations an assessment model for external evidence in occupational therapy research in terms of a triangular pyramid is being designed and put up for discussion. CONCLUSION: Evidence-based occupational therapy practice which meets the complex demands of clinical everyday practice can only be achieved by a systematic review of clinical-experimental, (quantitative) medical care and qualitative research.

Die Ursachen der terminalen Niereninsuffizienz im Kindesalter unterscheiden sich deutlich von denen des Erwachsenenalters. Die Therapie der Wahl besteht in der Nierentransplantation. In Deutschland wurden im Jahre 2003 117 Kinder und Jugendliche nierentransplantiert. Spezifische Probleme bestehen in der Immunsuppression und den daraus resultierenden Komorbiditaten im Kindesalter. Der vorliegende Beitrag gibt eine Ubersicht uber die Moglichkeiten und Probleme der Vorbereitung, der Transplantation und des weiteren Verlaufs von Nierentransplantationen im Kindesalter.

Sind ausreichend Erfahrungen mit der laparoskopischen Prostatektomie vorhanden, ist der Schritt zur laparoskopischen Zystektomie nicht mehr sehr gros. Die eigentliche Herausforderung besteht in der laparoskopischen Konstruktion der Harnableitung. Wir berichten in diesem Artikel uber Erfahrungen mit 11 laparoskopischen Zystektomien und der intrakorporalen Anlage eines Mainz Pouch II als kontinente Harnableitung bei Patienten mit einem muskelinvasiven Harnblasenkarzinom. Alle 11 Eingriffe konnten erfolgreich durchgefuhrt werden. Eine Konversion war nicht notwendig. Die mittlere Operationszeit betrug 6,7 h. Bis auf 2 Pouchfisteln wurden keine Komplikationen beobachtet. Sowohl die funktionellen als auch onkologischen Ergebnisse sind uberzeugend. Der wesentliche Vorteil des minimal invasiven Vorgehens ist die deutlich reduzierte Morbiditat mit kurzerer Rekonvaleszenz. Auserdem senkt der extrem niedrige Blut-, Elektrolyt- bzw. Flussigkeitsverlust den kardiovaskularen Stress enorm. Die laparoskopische radikale Zystektomie stellt derzeit die Grenze der technisch machbaren und sinnvollen Laparoskopie dar und sollte deshalb den Zentren mit entsprechender Expertise vorbehalten bleiben.

We present our experience with the first 5 patients who underwent radical cystectomy with bilateral pelvic lymphadenectomy and continent urinary diversion (rectal sigmoid pouch) performed with an intracorporeal laparoscopic technique at our center.There were 3 males and 2 females 59 to 65 years old with organ confined, muscle invasive transitional cell carcinoma of the bladder who underwent surgery. The procedure included pelvic lymph node dissection, radical cystectomy with prostate or uterus and tubal structures, creation of the rectal sigmoid pouch and bilateral stented antireflux implantation of the ureters into the pouch. Freehand laparoscopic suturing and in situ knot tying techniques were used exclusively. The mobilized specimens were removed in an endoscopy bag via the rectum or vagina. Laparotomy was not required.Operating time was 6.9 to 7.9 hours (median 7.4) and blood loss was 190 to 300 ml. (median 245). None of the 5 patients none needed blood transfusion. Oral intake was started on hospital day 3, ureteral stents were removed on day 8 and the pouch catheter was removed on day 9. The hospital stay was 10 days for all cases. Histopathological examination of the specimens revealed stage pT1 G3 urothelial carcinoma in case 1, pT2b G2 in cases 2 and 3, pT3a G2 in case 4 and pT3aG3 in case 5. The lymph nodes and resection margins were tumor-free. No intraoperative or postoperative complications were observed.To our knowledge, this is the first series of laparoscopic radical cystectomy with intracorporeal continent urinary diversion (rectal sigmoid pouch), and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with continent urinary diversion may become an alternative surgical method for treating select patients with localized muscle invasive bladder cancer.

Ermutigt durch die ersten erfolgreichen Berichte uber die laparoskopische radikale Prostatektomie haben wir diesen Eingriff im Juni 1999 in unser Operationsprogramm aufgenommen. Bis Ende November 2000 fuhrten wir insgesamt 145 dieser Eingriffe durch. Die Indikation zur laparoskopischen Prostatektomie entsprach genau der, die wir fur die offene Operation anwenden. Abdominelle Voroperationen, transurethrale Resektionen bzw. eine masige Adipositas sind keine Kontraindikationen. Eine Konversion zur offenen Operation war in keinem Fall erforderlich. Die postoperative Komplikationsrate betrug 11,7%, wobei es sich vorwiegend um Minorkomplikationen handelte. Auch hinsichtlich der Kontinenz und Potenz sind die Ergebnisse sehr gut. Unserer Meinung nach ist die laparoskopische radikale Prostatektomie eine echte Alternative zur offenen Operation, da sie eine Reihe von Vorteilen fur den Patienten und den Operateur aufweist.

Purpose: The laparoscopic access for radical prostatectomy offeres an alternative to the open surgical procedure with less morbidity. We report on our experience with 125 laparoscop

AIMS: Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time. METHODS AND RESULTS: In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosis > or = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors. CONCLUSION: Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare.

The aim of this study was to investigate if the concomitant administration of the positive inotropic drug enoximone (100 mg tid) has any effect on the morning through levels of the cardiac glycoside digoxin in 17 patients with congestive heart failure (NYHA II-IV). Plasma concentrations of digoxin were 1.05 +/- 0.37 ng/mL before enoximone, 0.95 +/- 0.31 ng/mL at the end of the enoximone treatment period of 1 week and 0.95 +/- 0.36 ng/mL 1 week after cessation of enoximone treatment. Thus, concomitant administration of enoximone had no effect on plasma concentrations of digoxin while on the other hand the hemodynamics as assessed by NYHA-classification and determination of the heart volume improved significantly.

Human parvovirus B19 is a common cause of benign erythema infectiosum (fifth disease) in otherwise healthy children. Immunocompromized patients are at risk of developing chronic infections leading to chronic hyporegenerative anemia. We report the case of a nine-year-old boy who presented five days after renal transplantation with seizures and signs of encephalitis on MRI. The clinical course was characterized by anemia and seroconversion for parvovirus B19 accompanied by a high viral load (>10(9) copies per milliliter). A transfusion of red blood cells that the patient required after transplantation was found to be negative for parvovirus B19, leaving the donated organ as the most likely source of infection. Reduction of the immunosuppressive regimen led to complete recovery of the patient with a stable RBC count upon discharge. Parvovirus B19 infections should be considered in the differential diagnosis of seizures after solid organ transplantation.

Background A 16-year-old white male with a history of obstructive uropathy presented to a pediatric outpatient clinic with a first syncope. At presentation, he had a hemoglobin level of 220 g/l, a serum erythropoietin level of 27.4 U/l and a serum creatinine level of 200.7 µmol/l (2.27 mg/dl). Investigations Physical examination, serum laboratory analysis, renal ultrasound, MRI, and 99mTc-MAG3 scintigraphy of the kidneys. Diagnosis Chronic renal insufficiency caused by obstructive hydronephrosis and accompanied by increased erythropoietin levels of renal origin and polycythemia. Management Serial phlebotomies and laparoscopic removal of the right hydronephrotic kidney.

We report on the observation of an anomalously high damping measured by a vibrating-wire resonator (VWR) immersed into superfluid at ultralow temperatures. The observed dissipation is orders of magnitude above that corresponding to friction with the dilute normal fraction and superfluid vortices. A clear pinning behavior is also observed, as well as a strong magnetic field dependence. Our analysis points to the interaction of the VWR with a planar topological defect, analogue to cosmological vacua defects, as proposed by Salomaa and Volovik.

Die laparoskopische Lebendspendernephrektomie (LDN) wurde vor 10 Jahren erstmals durchgefuhrt. Heute wird sie in vielen amerikanischen Zentren routinemasig praktiziert. In der vorliegenden Arbeit werden die verschiedenen Aspekte der LDN, deren Auswirkungen fur Spender, Organ, Empfanger und Operateur evaluiert. Es folgt die Literaturrecherche und -vergleich zum Thema laparoskopische Donornephrektomie und zu den verschiedenen Teilaspekten werden die Besonderheiten dieser Methoden und die eigenen Erfahrungen am aktuell grosten deutschen LDN-Zentrum Zentrum (Charite Berlin, Campus Mitte) dargestellt. Die laparoskopische Nierenentnahme beim lebenden Spender bietet die gleiche Sicherheit wie der offene Eingriff. Gleichzeitig bietet sie multiple Vorteile fur den Donor, wie verminderte Schmerzen und kurzere Rekonvaleszenz. Fur das gespendete Organ und den Empfanger sind keine Nachteile durch die neue Technik zu erwarten, sofern einige intra- und perioperative Masnahmen Anwendung finden. Technische Weiterentwicklungen bieten zudem dem Operateur ein mittlerweile breites Armentarium zur optimalen Durchfuhrung der LDN. Die LDN ist fur den Spender, das Organ, den Empfanger und den Operateur sicher. Kernpunkt einer optimalen LDN ist eine ausreichende Erfahrung in laparoskopisch-operativen Techniken und laparoskopischen urologischen Operationen.

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.

Once laparoscopic radical prostatectomy has been mastered, the step to performing a radical cystectomy is not that far. The challenge is to create the urinary diversion by laparoscopy. In this report we describe our experience with 11 laparoscopic radical cystectomies and intracorporeal construction of a continent urinary diversion (Mainz pouch II) as a treatment option in patients with muscle-invading bladder cancer. All 11 procedures could be performed successfully. A conversion to open surgery was not required in any case. The mean surgery time was 6.7 h. Except for two pouch fistulas we did not observe any intra- or postoperative complications. The functional as well as the oncological results are convincing. Less morbidity and faster recovery are the main advantages of this minimally invasive procedure. In addition, the low levels of blood loss, fluid shifts, and electrolyte loss considerably reduce cardiovascular stress. Radical cystectomy and construction of a continent urinary diversion represent the limit of technically feasible laparoscopy and should be done exclusively in specialized centers.

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

The laparoscopic access for radical prostatectomy offers an alternative to the open surgical procedure with less morbidity. We report on our experience with 125 laparoscopic prostatectomies, especially with respect to making the laparoscopic approach a routine procedure and with a view to the oncological and functional results.From June 1999 to September 2000, we performed 125 laparoscopic prostatectomies. These included only patients with cancer stages T1 or T2. The mean PSA concentration was 10.5 ng/ml. Forty-four percent of the patients had undergone previous abdominal and 19% previous transurethral surgery. For our laparoscopic prostatectomies we used the descending technique. Free-hand laparoscopic suturing and in situ knot-tying technique were used for the urethrovesical anastomosis. The mobilized specimens were removed in an endobag via a muscle splitting incision.All 125 procedures could be completed successfully. No case required conversion to open surgery. The average operating time was 255 min, the last 40 procedures taking 200 min only. Mean blood loss was 185 ml. Two patients (2%) required postoperative blood transfusion. After an initial learning curve, catheter remained in place for an average of 5.5 days, and the average postoperative stay in hospital was 8 days. Intraoperative complications were seen in 5 patients (4%). In 13 patients (10.4%) postoperative complications were observed. 86% of the patients are continent 6 months postoperatively. Preservation of the neurovascular bundle and sexual potency is possible.Laparoscopic radical prostatectomy is an ambitious procedure with a steep learning curve, especially for the laparoscopic dissecting and suturing technique. The excellent sight for dissection results in a reduced blood loss and faster convalescence with an overall lower morbidity. Also with regard to oncological and functional (continence) results the minimally invasive access is at least equivalent to the open procedure. In our opinion, laparoscopic prostatectomy will be the future method of choice for radical prostatectomy.

Encouraged by the groups in Paris, we performed 145 laparoscopic radical prostatectomies between June 1999 and the end of November 2000. The indication for laparoscopic prostatectomy is the same as for open surgery: an organ-confined cancer. Previous abdominal surgery, transurethral resection, and/or relative adiposity are not considered to be contraindications for this laparoscopic procedure. The mean operating time was 255 min; the last 60 procedures took an average of 200 min. In no case was it necessary to convert to open surgery. Worthy of note was the low blood loss of 185 ml on average so that in 98% of the patients no blood transfusion was required. After completing the learning curve, the average indwelling catheter time was only 5.5 days. The postoperative complication rate was 11.7%, consisting mainly of minor complications. Also with regard to continence and potency, the results were representative. Postoperatively, 75%, 86%, 92%, and 93% of the patients were continent after 3, 6, 9, and 12 months, respectively. In our opinion, laparoscopic radical prostatectomy is an alternative to open prostatectomy, offering a number of advantages for the patient and surgeon as well.

Technical and manual progress made in recent years now enables large uro-oncological procedures to be performed by means of laparoscopy. We report the first successful radical laparoscopic cystectomy and laparoscopic construction of a continent urinary diversion. Laparotomy can be avoided completely. The advantages are clear reduction of blood loss and postoperative morbidity with faster convalescence.

To evaluate the diagnostic utility of free prostate specific antigen (fPSA), alpha-1- antichymotrypsin-bound PSA (PSA-ACT), complexed PSA (cPSA), and including their associated ratios to total PSA (tPSA) in serum for discrimination between prostate cancer (PCa) and benign prostatic hyperplasia (BPH).A total of 166 white men (age: 65-88 years) with a tPSA between 2 and 20 microg/l were retrospectively analysed. Serum concentrations of tPSA, fPSA, PSA-ACT and cPSA were measured in 118 untreated PCa patients and 48 patients with BPH. The tPSA and cPSA concentrations were measured with the Bayer Immuno 1 system (Bayer Diagnostics, Tarrytown, USA). The Elecsys system 2010 (Roche Diagnostics, Mannheim, Germany) was used for determination of tPSA and fPSA. The PSA-ACT assay is a newly, developed prototype assay on the ES system (Roche Diagnostics, Mannheim, Germany).For statistical analysis only patients with tPSA between 2 and 20 microg/l were enrolled. The median concentrations of tPSA (Bayer: PCa 7.36 microg/l, BPH 4.03 microg/l; Roche: PCa 7.75, BPH 4.13), PSA-ACT (PCa 6.98, BPH 3.18) and cPSA (PCa 6.46, BPH 3.20) were significantly different. The median ratios of fPSA/tPSA (PCa 12.8 vs. BPH 22.4%), PSA-ACT/tPSA (PCa 89.8 vs. BPH 76.1%) and cPSA/tPSA (PCa 90.5 vs. BPH 81.7%) were significantly different between PCa and BPH patients. Using the areas under the curves, receiver operating characteristics analysis (tPSA: 2-20 microg/l) for discrimination between PCa and BPH showed that the ratios fPSA/tPSA (area under the curve: 0.77), PSA-ACT/tPSA (0.72) and cPSA/tPSA (0.78) were significantly different from tPSA (Bayer: 0.53; Roche: 0.55). PSA-ACT (0.64) and cPSA (0.59) alone were not significantly different from tPSA. The calculated ratios fPSA/tPSA, PSA-ACT/tPSA and cPSA/tPSA were not significantly different.The determination of PSA-ACT or cPSA and the associated ratios do not improve the diagnostic impact to discriminate between PCa and BPH compared to fPSA/tPSA ratio. The ratios PSA-ACT/tPSA or cPSA/tPSA can be considered to be alternative tools of fPSA/tPSA.

This study tests the hypothesis that abrupt reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass produces an unintended reoxygenation injury that: (i) nullifies the cardioprotective effects of blood cardioplegia; and (ii) is avoidable by adding the antioxidants, N-(2-mercaptopropionyl)-glycine (MPG) plus catalase to the cardiopulmonary bypass prime. Twenty immature piglets (aged 2-3 weeks) underwent 30 min of blood cardioplegic arrest (BCP) with standard clinical blood cardioplegia (hypocalcaemic, alkalotic, hyperosmolar, substrate-enriched). Six piglets remained normoxaemic (BCP). Fourteen others were made hypoxic (PO2 20-30 mmHg) for up to 2 h by lowering ventilator FiO2 (5-7%) before undergoing reoxygenation on cardiopulmonary bypass at PO2 400 mmHg. In eight animals, the pump prime was not supplemented with antioxidants (Reox + BCP), whereas MPG (80 mg/kg) and catalase (CAT; 5 mg/kg) were added to the pump prime in the other six (MPG/CAT). Myocardial function (end-systolic elastance, conductance catheter), oxidant damage (myocardial conjugated diene production), oxygen consumption and antioxidant reserve capacity were evaluated. Blood cardioplegic arrest caused no functional or biochemical changes in controls without preceding hypoxia. In contrast, hypoxia and reoxygenation in animals undergoing the same blood cardioplegic protocol (Reox + BCP) caused profound myocardial dysfunction, as end-systolic elastance recovered only to 21(2)% (P0.05 versus control) of baseline values. Additionally, it reduced antioxidant reserve capacity (malondialdehyde, MDA at 4.0 mM of t-BHP: 1342(59) (P0.05 versus control) versus 788(53) mmol/g protein), and led to significantly greater production of conjugated dienes during warm induction (42(4.4) (P0.05 versus control) versus 3.3(1.4) A233 nm/100 g per min) and reperfusion (22(2.7) (P0.005 versus control) versus 2(0.6) A233 nm/100 g per min). Conversely, supplementation of MPG plus catalase to the pump prime reduced lipid peroxidation (conjugated diene production during warm induction: 22.3(7) A233 nm/100 g per min P0.05 versus Reox + BCP), restored antioxidant reserve capacity (MDA at 4.0 M of t-BHP: 975(139) mmol/g protein P0.05 versus Reox + BCP) and allowed almost complete functional recovery (80(8)%). Abrupt reoxygenation of hypoxaemic immature hearts on cardiopulmonary bypass causes oxidant damage, nullifies the cardioprotective effects of blood cardioplegia, and leads to reduced myocardial contractility. Antioxidant supplementation of the cardiopulmonary bypass prime avoids these detrimental effects, and results in improved biochemical and functional status.

Angiographic studies on the natural course of both focal and diffuse coronary atherosclerosis have not been performed before, but can both be assessed by quantitative coronary angiography. The objective of this study was to describe the natural course of focal and diffuse coronary atherosclerosis over time.In 129 patients with mild coronary artery disease, but not on lipid-lowering medication, three coronary angiograms were made each 2 years apart. Nine hundred and sixty five angiographically diseased and non-diseased segments were analysed by quantitative coronary angiography. Mean lumen diameter and minimal lumen diameter were used as measures of diffuse and focal coronary atherosclerosis. Mean lumen diameter and minimum lumen diameter decreased by 0.02 and 0.03 mm per year. The rate of progression was similar in the angiographically non-diseased, as in the mildly and moderately diseased segments. Progression of diffuse coronary atherosclerosis was largest in severely stenosed lesions (percentage diameter stenosisor = 50%) and in the right coronary artery with a loss of 0.19 mm and 0.16 mm in mean lumen diameter. Progression of focal disease was most prominent in new and mild lesions and the right coronary artery, with a decrease in minimum lumen diameter of 0.34 mm and 0.22 mm. In most subgroups, progression occurred gradually over time. On a per segment level, progression and the occurrence of new lesions occurred in 4.4% and 4.2%. Regression and disappearance of a lesions was found in 2.3% and 1.9%. On a per patient level, 36% were progressors, 12% had a mixed response, 36% were stable, and 16% were regressors.Diffuse and focal coronary atherosclerosis progressed at the same rate in the first and second 2 years in stenosed and non-stenosed segments. The rate of coronary atherosclerosis progression was small, but was higher for focal than for diffuse disease. A minority of lesions progressed and spontaneous regression was rare.

About three and a half years after direct suture of a secundum atrial septal defect (ASD) the now 72-year-old patient developed heart failure with pulmonary congestion and pleural effusion which responded to medical treatment. The electrocardiogram showed atrial fibrillation with an irregular ventricular rate and right bundle branch block. Right heart catheterization established recurrence of the ASD with a left to right shunt of 60% (Qp/Qs = 2.5) and a pulmonary artery pressure of 45/12 mmHg. Because of the clinical state, the risk of re-operation and the suitable anatomy, non-operative percutaneous transvenous catheter closure of the defect with a double-umbrella device was indicated. Following this procedure the cardiomegaly regressed, while colour-Doppler echocardiography demonstrated a minimal residual left to right shunt. The pulmonary artery pressure had fallen to 32/13 mmHg. Three months later the patient was without symptoms and resumed her usual activity. The ECG now showed sinus rhythm, and there was no evidence of a shunt. Anticoagulation with acetyl salicylic acid (100 mg daily) was continued for 3 months.

The aim of this study was to clarify a) whether the behaviour of functional dead space ratio (VD/VE), alveolo-arterial difference of oxygen tensions (AaDO2) and the venous admixture ratio (QVA/Qt) differed at rest and during submaximal exercise, between patients with pulmonary emphysema and interstitial pulmonary fibrosis as well as from the respective findings in healthy controls, and b) whether a differentiation between these two diseases could be achieved by investigations of complex pulmonary gas exchange. Eleven patients with pulmonary fibrosis (F), which had been diagnosed by pulmonary biopsies, 11 patients with pulmonary emphysema (E) and 11 healthy controls (C) were subjected to conventional pulmonary function tests (PFTs: spirometry, bodyplethysmography, DCO) immediately followed by examinations of pulmonary gas exchange conducted at rest and during an incremental submaximal cycle spiroergometry (ERGO). With normal PFTs for C, vital capacity was diminished in F and the 1" timed vital capacity (FEV1) as well as Tiffeneau's index were reduced in E, while air way resistance and functional residual capacity were augmented in the latter group. In all patients the CO-diffusing capacity was lower compared to C, however, without differences between F and E. In both E and F, the arterial O2 tension were lower at rest as well as during ERGO when compared to C, whereas VD/VE, QVA/Qt and AaDO2 as well as the specific ventilation for O2 were higher, respectively. Alveolar ventilation was similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The identification of disease genes via molecular DNA cloning has revolutionized human genetics and medicine. Both the candidate gene approach and positional cloning have been used successfully. The defects causing Huntington's disease, facioscapulohumeral muscular dystrophy, piebaldism, Hurler/Scheie syndrome, one form of autosomal recessive retinitis pigmentosa, and a second locus for autosomal dominant polycystic kidney disease have recently been localized to chromosome 4. In addition to the rapid progress in the cloning of the 203-megabase chromosome, the presence of more than 60 closely spaced microsatellites on this chromosome will undoubtedly lead to the localization of additional disease genes. In order to consider cloned genes as potential candidates for disorders assigned to chromosome 4, it is important to collect and order all genes with respect to their chromosomal localization. Analysis of cytogenetically visible interstitial and terminal deletions should also be helpful in defining new disease gene loci and in mapping novel genes. These data represent the status quo of the integrated molecular map for chromosome 4.

To elucidate the mechanism of anti-ischaemic and anti-anginal action of angiotensin-converting-enzyme inhibitors, a randomized double-blind study was undertaken in 30 consecutive patients (27 men, 3 women; mean age 58 [28-70] years) with stable angina and at least 50%, angiographically well demonstrated, stenosis of one of the main coronary artery branches. They received an intracoronary infusion of either 0.5 mg captopril (n = 16) or of a placebo (n = 14) to see whether in this form of application the drug could cause an acute dilatation of a coronary stenosis. The diameter before captopril administration was 1.40 +/- 0.63 mm, while 1, 5 and 10 min after infusion it was 1.49 +/- 0.58 mm, 1.30 +/- 0.54 mm and 1.41 +/- 0.59 mm (not significant). There was also no significant difference between captopril and the placebo. The absence of effect with captopril may be due to insufficient liberation of endothelium-derived relaxing factor in an arteriosclerotic coronary segment.

We analysed the case histories of 149 patients who had been given hospital treatment for psychic disorders. Among them we found nine patients (6%) with stress factors caused by the radical historical upheavals in the former GDR, which had played a main role in the pathogenesis of the psychic disorders. In these cases it was above all stress factors which indirectly affected the child through the family situation.

Three patients developed left main stem stenosis within some months after aortic valve replacement. In all of them diagnosis was confirmed by angiography and bypass surgery was performed successfully. Left main stem stenosis is a rare complication of aortic valve replacement and is due to cannulation and perfusion of the coronary arteries. The mechanism is probably injury of the vessel wall due to the perfusion-catheter, followed by intimal hyperplasia. A similar mechanism is assumed for restenosis after transluminal coronary angioplasty.

Sixteen patients undergoing PTCA of a significant lesion of the left anterior descending coronary artery received either 0.3 mg nisoldipine or placebo intravenously. Immediately before and during balloon inflation the following parameters were measured: aortic pressure, post-stenotic pressure, coronary occlusion pressure, diastolic pulmonary artery pressure, coronary sinus flow (thermodilution), and intracoronary ECG. After placebo there were no statistically significant changes. Nisoldipine led to a decrease in aortic pressure from 109 +/- 12 to 93 +/- 11 mm Hg (p less than 0.05) before, and from 103 +/- 14 to 92 +/- 8 mm Hg (NS) during balloon inflation. In contrast, coronary occlusion pressure remained unchanged. Heart rate increased from 80 +/- 13 to 96 +/- 16/min before (p less than 0.05), and from 87 +/- 18 to 97 +/- 17/min during balloon inflation (NS). Coronary sinus flow was increased from 95 +/- 16 to 116 +/- 13 ml/min before balloon inflation (p less than 0.01), and from 70 +/- 25 to 86 +/- 26 ml/min during balloon inflation (NS). ST-segment depression or elevation, severity of angina pectoris, and the diastolic pulmonary artery pressure remained unchanged. Thus, 0.3 mg nisoldipine led to a peripheral vasodilatation. While the aortic pressure decreased, coronary occlusion pressure remained unaffected. This could be explained by a marked dilatation of collateral vessels due to nisoldipine. However, myocardial ischemia remained unaffected as a result of the constant coronary occlusion pressure.

A 6-month double-blind study was conducted in 26 patients suffering from a severe obstructive disturbance of ventilation and respiratory insufficiency to find out the behaviour of blood gases and pulmonary haemodynamics under Almitrin treatment compared with placebo. The acute administration of 75 mg Almitrin resulted in a significant increase of PaO2 by 11.7 mmHg, as well as of PAPR by 4.4 mmHg. Statistical significance was seen only for the systolic pressure of the a. pulmonalis. After subsequent 6-month treatment with 3 x 25 mg Almitrin, a significantly higher PaO2 is seen at T6 than in the control group. Another additional administration of 75 mg Almitrin results in a further increase of PaO2 by 7.7 mmHg. At T6 the behaviour of pulmonary haemodynamics is identical in both groups A and P.