Erratum: Ultrafast Doublon Dynamics in Photoexcited 1T-TaS_{2} [Phys. Rev. Lett. 120, 166401 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.120.166401.

Ultrafast Doublon Dynamics in Photoexcited 1T-TaS_{2}.

Strongly correlated materials exhibit intriguing properties caused by intertwined microscopic interactions that are hard to disentangle in equilibrium. Employing nonequilibrium time-resolved photoemission spectroscopy on the quasi-two-dimensional transition-metal dichalcogenide 1T-TaS_{2}, we identify a spectroscopic signature of doubly occupied sites (doublons) that reflects fundamental Mott physics. Doublon-hole recombination is estimated to occur on timescales of electronic hopping ℏ/J≈14 fs. Despite strong electron-phonon coupling, the dynamics can be explained by purely electronic effects captured by the single-band Hubbard model under the assumption of weak hole doping, in agreement with our static sample characterization. This sensitive interplay of static doping and vicinity to the metal-insulator transition suggests a way to modify doublon relaxation on the few-femtosecond timescale.

Contrast-enhanced spectral mammography versus MRI: Initial results in the detection of breast cancer and assessment of tumour size.

OBJECTIVES: To compare mammography (MG), contrast-enhanced spectral mammography (CESM), and magnetic resonance imaging (MRI) in the detection and size estimation of histologically proven breast cancers using postoperative histology as the gold standard. METHODS: After ethical approval, 80 women with newly diagnosed breast cancer underwent MG, CESM, and MRI examinations. CESM was reviewed by an independent experienced radiologist, and the maximum dimension of suspicious lesions was measured. For MG and MRI, routine clinical reports of breast specialists, with judgment based on the BI-RADS lexicon, were used. Results of each imaging technique were correlated to define the index cancer. Fifty-nine cases could be compared to postoperative histology for size estimation. RESULTS: Breast cancer was visible in 66/80 MG, 80/80 CESM, and 77/79 MRI examinations. Average lesion largest dimension was 27.31 mm (SD 22.18) in MG, 31.62 mm (SD 24.41) in CESM, and 27.72 mm (SD 21.51) in MRI versus 32.51 mm (SD 29.03) in postoperative histology. No significant difference was found between lesion size measurement on MRI and CESM compared with histopathology. CONCLUSION: Our initial results show a better sensitivity of CESM and MRI in breast cancer detection than MG and a good correlation with postoperative histology in size assessment. KEY POINTS: • Contrast-enhanced spectral mammography (CESM) is slowly being introduced into clinical practice. • Access to breast MRI is limited by availability and lack of reimbursement. • Initial results show a better sensitivity of CESM and MRI than conventional mammography. • CESM showed a good correlation with postoperative histology in size assessment. • Contrast-enhanced spectral mammography offers promise, seemingly providing information comparable to MRI.

Detection of microcalcifications in women with dense breasts and hypoechoic focal lesions: comparison of mammography and ultrasound.

PURPOSE: Microcalcifications in the breasts can point to breast cancer. However, there is great morphologic variety, and microcalcifications do not always correlate with malignancy. We conducted a prospective study to compare ultrasound and mammography in the detection of microcalcifications following sonographic diagnosis of a hypoechoic focal lesion in women with dense breast composition. MATERIALS AND METHODS: A total of 104 lesions potentially associated with microcalcifications (82 malignant and 23 benign lesions) were included in the study. The breast was examined by ultrasound (9 MHz, Aplio XG/500) with additional use of MicroPure imaging for the demonstration and evaluation of microcalcifications. The presence of a focal lesion was verified and microcalcifications were counted at ultrasound and mammography by blinded readers. The sensitivity and specificity were determined, and ROC analysis and AUC analysis were performed. RESULTS: The women had a median age of 51 years. The average number of microcalcifications detected by sonography (2.12 ±â€Š2.77) and mammography (3.59 ±â€Š6.35) was not significantly different (p > 0.05). Correlation of the techniques was adequate (Pearson's r = 0.616, p < 0.0001; Spearman's rho = 0.654, p < 0.0001). The intraclass correlation coefficient was K = 0.382 ±â€Š0.072 (p < 0.0001), also indicating adequate agreement of both techniques. The sensitivity and specificity were 70%/30% for MicroPure and 45%/55% for mammography. The positive predictive value of mammography was superior to that of MicroPure (88% vs. 78%). CONCLUSION: The sonographic detection of microcalcifications with MicroPure imaging in breasts with a hypoechoic focal lesion correlates well with digital mammography.

Diagnostic performance of a Near-Infrared Breast Imaging system as adjunct to mammography versus X-ray mammography alone.

OBJECTIVES: Radiologist reader performance for breast cancer detection using mammography plus Near-Infrared Breast Imaging (NIBI) was compared with mammography alone. METHODS: Two hundred seventy-six consecutive patients with suspected breast lesions underwent both mammography and NIBI. Four blinded radiologists independently first reviewed the mammograms alone. Readers subsequently reviewed the mammograms in combination with NIBI. The diagnostic benefit of NIBI as an adjunct to mammography was determined by performing receiver operating characteristics (ROC) analyses for each reader based on BI-RADS categories (Breast Imaging Reporting and Data System) and LOS (level of suspicion) scores. Additionally, a multireader-multicase (ROC) analysis of variance (ANOVA) was carried out. RESULTS: For the LOS-based analysis, the combination of mammography and NIBI resulted in a slightly larger area under the curve (AUC) for all four readers. The analysis based on BI-RADS categories also demonstrated a slight increase in AUC for three readers for the combination of mammography and NIBI compared with mammography alone. For the fourth reader, AUC was smaller for the combination compared with mammography alone. Neither for the separate ROC-analyses nor for the ANOVA, significant differences between the two methods were obtained. CONCLUSIONS: The combination of mammography and NIBI did not perform significantly better than mammography alone. KEY POINTS: The intrinsic contrast provided by optical breast imaging may be inadequate We found slightly (but nonsignificant) higher accuracy for optical imaging and mammography compared with mammography alone. Contrast agents might be necessary to improve the performance of optical breast imaging.

[Sonographic detection of microcalcifications - potential of new method]. / Sonografische Mikrokalkdetektion - Potenzial einer neuen Methode.

PURPOSE: Does the easier microcalcification detection (EMD) method enable sonographic visualization of microcalcifications in breast core biopsy specimens compared with mammography? MATERIALS AND METHODS: In a prospective randomized study, 105 core biopsy specimens obtained with stereotactic guidance were examined by mammography and ultrasound. EMD is integrated in a high-end ultrasound system and uses three level settings (0 - 2 blue, 3 - 5 violet, and 6 - 8 black-and-white; 14 MHz). Detection of microcalcifications per core specimen was determined for ultrasound and mammography. EMD image quality was rated on a scale of 1 - 9. ANOVA and Sidak post-hoc testing, Pearson regression analysis (r), and Spearman rank correlation (rho) were performed. The intraclass correlation coefficient (ICC) was calculated, and an ROC analysis was conducted. RESULTS: The blue color map 1 was assigned the highest mean score of 1.5 ± 0.7 (p< 0.05 compared with black-and-white and violet). There was good correlation between the two modalities (r= 0.708 and rho= 0.694) with detection of 3.5 ± 3.1 microcalcifications per specimen by ultrasound versus 4.3 ± 4.8 by mammography (p> 0.05). The ICC of 0.773 indicates little disagreement between the two modalities. ROC analysis showed mammography to be superior to ultrasound compared with histological detection of microcalcifications (AUC= 0.837 vs. AUC= 0.728). CONCLUSION: Sonographic detection of microcalcifications in stereotactic biopsy specimens using the EMD method correlates well with digital mammography. Mammography is slightly superior.

Significant differentiation of focal breast lesions: raw data-based calculation of strain ratio.

PURPOSE: We compared elastography, B-mode ultrasound and mammography to determine whether raw data calculation of strain ratios (SRs) can further improve the differentiation of focal breast lesions. MATERIALS AND METHODS: 201 women with histologically proven focal breast lesions (85 benign, 116 malignant) were included at two German breast centers. Patients underwent a standardized ultrasound procedure using high-end ultrasound system with a 9-MHz broadband linear transducer. Two experienced readers analyzed the B-mode scans and mammograms using the BI-RADS criteria, while elastograms were analyzed using the Tsukuba score. SRs were calculated from a tumor-adjusted ROI and a comparable ROI placed in the lateral fatty tissue. The sensitivity, specificity, and cutoff values were calculated for SRs (ROC analysis). RESULTS: The median age was 53 years. The sensitivity and specificity were 85 %/ 60 % for B-mode scanning, 85 %/ 68 % for elastography, 78 %/ 62 % for mammography, and 95 %/ 74 % for SRs. An SR cutoff value of 2.27 (AUC 0.907) allowed significant differentiation (p < 0.001) between malignant and benign lesions. The quantitative SR calculation was superior to subjective interpretation of B-mode scans and sonoelastograms with a positive predictive value of 83 % versus 78 % and 74 %, and equal to mammograms. CONCLUSION: Strain ratio calculation contributes to the standardization of sonoelastography with high sensitivity and allows significant differentiation between benign and malignant breast lesions with a higher specificity compared to B-mode, subjective evaluation of elastography and mammography.

Momentum-space signatures of Berry flux monopoles in the Weyl semimetal TaAs.

Since the early days of Dirac flux quantization, magnetic monopoles have been sought after as a potential corollary of quantized electric charge. As opposed to magnetic monopoles embedded into the theory of electromagnetism, Weyl semimetals (WSM) exhibit Berry flux monopoles in reciprocal parameter space. As a function of crystal momentum, such monopoles locate at the crossing point of spin-polarized bands forming the Weyl cone. Here, we report momentum-resolved spectroscopic signatures of Berry flux monopoles in TaAs as a paradigmatic WSM. We carried out angle-resolved photoelectron spectroscopy at bulk-sensitive soft X-ray energies (SX-ARPES) combined with photoelectron spin detection and circular dichroism. The experiments reveal large spin- and orbital-angular-momentum (SAM and OAM) polarizations of the Weyl-fermion states, resulting from the broken crystalline inversion symmetry in TaAs. Supported by first-principles calculations, our measurements image signatures of a topologically non-trivial winding of the OAM at the Weyl nodes and unveil a chirality-dependent SAM of the Weyl bands. Our results provide directly bulk-sensitive spectroscopic support for the non-trivial band topology in the WSM TaAs, promising to have profound implications for the study of quantum-geometric effects in solids.

Time- and momentum-resolved photoemission studies using time-of-flight momentum microscopy at a free-electron laser.

Time-resolved photoemission with ultrafast pump and probe pulses is an emerging technique with wide application potential. Real-time recording of nonequilibrium electronic processes, transient states in chemical reactions, or the interplay of electronic and structural dynamics offers fascinating opportunities for future research. Combining valence-band and core-level spectroscopy with photoelectron diffraction for electronic, chemical, and structural analyses requires few 10 fs soft X-ray pulses with some 10 meV spectral resolution, which are currently available at high repetition rate free-electron lasers. We have constructed and optimized a versatile setup commissioned at FLASH/PG2 that combines free-electron laser capabilities together with a multidimensional recording scheme for photoemission studies. We use a full-field imaging momentum microscope with time-of-flight energy recording as the detector for mapping of 3D band structures in (kx, ky, E) parameter space with unprecedented efficiency. Our instrument can image full surface Brillouin zones with up to 7 Å-1 diameter in a binding-energy range of several eV, resolving about 2.5 × 105 data voxels simultaneously. Using the ultrafast excited state dynamics in the van der Waals semiconductor WSe2 measured at photon energies of 36.5 eV and 109.5 eV, we demonstrate an experimental energy resolution of 130 meV, a momentum resolution of 0.06 Å-1, and a system response function of 150 fs.

Pyomyositis in a Patient with IgA Nephropathy and Kidney Transplant.

Infections are among the most common complications transplant physicians face when dealing with solid organ transplant recipients. We present a case of pyomyositis caused by Staphylococcus aureus in a patient with IgA nephropathy and a kidney transplant, under treatment with mTOR inhibitors and prednisone. This entity is a rare intramuscular infection, given the resistance of healthy muscle to colonization. We review the most frequent agents, the diagnostic algorithm, and therapeutic alternatives. We also comment on the role of mTOR inhibitors in this case as possible predisposing factor for the infection.

Predictive and Comparative Study Between Clinic Consensus Document for Pancreas Acceptance and Predictive Value of Preprocurement Pancreas Allocation Suitability Score (P-PASS).

The strict selection of pancreas for transplant has forced the development of different documents to select the suitable organ in order to minimize the risks and complications of the transplant. In 2008, Eurotransplant published the Preprocurement Pancreas Allocation Suitability Score (P-PASS) for pretransplant selection. In 2001 the Hospital Clinic of Barcelona developed a Clinical Consensus Document (CCD). OBJECTIVES: We aimed to analyze the predictive decision of the pancreas acceptance to offers received in the hospital, according to the CCD criteria and compare it with the recommended value of suitability for accepting the pancreas according to the P-PASS value. MATERIAL AND METHODS: We performed a retrospective comparative study between the criteria of selection of the CCD for pancreas from 2016-2017 in comparison with the values obtained if the P-PASS had been used: ≤ 17, acceptance criteria and P-PASS; > 17, risk criteria. We defined the organ reported as rejected or accepted. The accepted organ could be procured and transplanted or discarded. RESULTS: With the CCD criteria, 7 more organs were transplanted than if we only applied the potential P-PASS criteria. In contrast, P-PASS would have ruled out an additional 9% of pancreases in relation to CCD criteria. CONCLUSIONS: According our experience, it is difficult to find an adequate prediction model to select pancreas for transplantation. The application of the DCC criteria increases the number of organs valid for transplantation. At present, new criteria should be re-evaluated within multicenter studies.

Late Onset Graft Plasmacytoma-Like PTLD Presenting as Acute Hyperglycemia in a Kidney-Pancreas Transplant Recipient.

Allograft infiltration has been described in up to 20% of all patients with posttransplant lymphoproliferative disorder (PTLD), most representing EBV-positive B-cell lymphomas. Plasma cells are often observed in humoral rejection biopsies, but graft infiltration by plasmacytoma-like PTLD is rare. We report the case of a 54-year-old simultaneous pancreas-kidney transplant recipient (immunosuppression: OKT3, methylprednisolone, cyclosporine, and azathioprine), diagnosed with an IgG-kappa monoclonal gammopathy of undetermined significance eighteen years after transplant. Nine months later, pancreas allograft biopsy performed due to new-onset hyperglycemia (HgA1C 8.6%, C-peptide 6.15ng/mL and anti-GAD 0.9UI/mL) revealed a monotypic plasma cell infiltrate, CD19, CD79a, CD138 positive, with IgG-kappa light chain restriction, and EBV negative. PET-scan FDG uptake was limited to pancreas allograft. Tumor origin could not be established (using DNA microsatellite analysis). Despite treatment with bortezomib and dexamethasone, patient eventually died one month later. This is the first report of a late onset extramedullary plasmacytoma involving a pancreas allograft.

[Mammography screening in Germany]. / Mammographiescreening in Deutschland.

Available data suggest that early detection of breast cancer by mammography screening can reduce mortality by about 25%. Intensified monitoring of women with a family history of breast cancer and regular general screening have recently been introduced in Germany. The screening program is expected to be fully established by 2008. Following its successful introduction (participation rates between 65 and 80%), the German screening program will be conducted and evaluated in accordance with the European guidelines. At least in the screening trials that were conducted prior to the now established screening program the quality criteria were more than fulfilled (e.g. cancer detection rate in Bremen 8.7, Wiesbaden 9.4, Weser-Ems region 8.3/1000). Additional parameters that can be taken into account for quality assurance are the overdiagnosis bias, lead time bias, length bias and selection bias. Moreover, there are some factors that are specific to the German program compared with the breast cancer screening programs already established in other countries. One of these is the intensified screening program for high-risk women (ca. 5% of all carcinomas) and as a result fewer women with an increased genetic risk of breast cancer will be represented in the general screening program. The German screening program involves only a few university centers and hospital-based physicians, which may have adverse effects on research and development as well as mammography training in the future. Therefore, the screening program should also provide for the investigation of new techniques or emerging techniques (e.g. CAD systems in screening mammography) in the future.

Modularity and Blended Methodology on Master Education for Donation and Transplantation.

Transplant Procurement Management and the University of Barcelona has offered a Master of Donation and Transplantation degree since 2004. The aim of this study is to analyze the number of participants, their profiles, and scores to evaluate improving measures introduced since 2011, when the modular structure was stablished. The data is organized in 3 groups: number of participants, profile, and scores in each module. The variables for the profile are gender, nationality, and background. According to the number of participants, 127 professionals were trained since 2011, with a decrease in the last classes (21; 20; 15). Regarding their profiles, from 2011 until 2016 the proportion of women was higher (63.13%). The background heterogeneity was an average of 4 different backgrounds in each edition, and medicine was most frequent background for students (58.27%). Participants were from 37 countries, mostly from the United States (45.6%) and Europe (40.9%). As for the scores, participants were evaluated in 4 modules (Donation, Transplantation, Management, and Tissue Banking), an internship, and a final master dissertation. The Donation module presented the lowest score (7.45/10) and the Transplantation module the highest (8.22/10). Considering that the main characteristics of the master's degree are the participants' internationality and heterogeneity, improvement measures must continue focusing on flexibility in the module selection and promoting the online modality.

Sirolimus monotherapy as maintenance immunosuppression: single-center experience in 50 kidney transplant patients.

INTRODUCTION: Chronic allograft nephropathy, cardiovascular mortality, and posttransplant malignancy are complications of conventional immunosuppression after kidney transplantation. We reported the feasibility of maintenance monotherapy with sirolimus (SRL) in a pilot experience. The aim was to study safety and feasibility of SRL maintenance monotherapy in 50 kidney transplant patients. METHODS: All patients from our center with at least 6 months follow-up on SRL monotherapy were included. During the first month after start of SRL monotherapy, follow-up visits were performed weekly, then each month for the following 2 months. Each follow-up visit included a physical exam and laboratory screening. RESULTS: Mean follow-up on SRL monotherapy was 34.7 +/- 14.9 months. The time between transplantation until start of monotherapy was 7.7 +/- 3.3 years. No rejections occurred. During follow-up, two patients died of cardiovascular disease (already diagnosed before monotherapy); one, of previously diagnosed posttransplant malignancy and one, of hepatitis C-related liver failure. Glomerular filtration rate (GFR) was 53 mL/min x 1.73 m2 at start of monotherapy and 50 mL/min x 1.73 m2 after 4 years. Proteinuria was 632 +/- 562 mg/24 hours at 4 years. During the follow-up, no significant changes in the lipid profile, glycemia, or hemoglobin occurred. CONCLUSIONS: Sirolimus monotherapy is safe in a selected group of immunological low-risk patients without increasing the risk of rejection.

Conversion from calcineurin inhibitors to sirolimus in kidney transplant patients reduces the urinary transforming growth factor-beta1 concentration.

INTRODUCTION: Chronic allograft dysfunction (CAD) is the main cause of late transplant failure. Although several etiologies have been postulated, toxicity for calcineurin inhibitors (CNIs) is one of the most important causes of CAD, characterized by arteriolar hyalinosis, luminal narrowing, increased glomerulosclerosis, and tubulointerstitial damage. It's known that in transplant patients with CAD, fibrogenic mediators such as transforming growth factor beta (TGF-beta) are increased. Sirolimus is an immunosuppressive agent with a distinct mechanism of action compared with CNI. AIM: This study assessed variations in levels of fibrogenic mediators among CAD patients treated with CNIs, before and after conversion to sirolimus. PATIENTS AND METHODS: We studied twelve renal transplant patients with CAD on CNI treatment. TGF-beta in plasma and urine, endothelin-1, and vascular endothelial growth factor (VEGF) were studied before and 8 months after conversion to sirolimus treatment. RESULTS: TGF-beta urine levels decreased from 24.7 +/- 11.2 to 12.8 +/- 5.1 ng/24 h (P = .049). In plasma, a similar decrease trend was observed (22.2 +/- 32 to 10.3 +/- 3 ng/mL), although it was not significant (P = .079). Endothelin-1 showed a decrease (8.1 +/- 3 to 5.2 +/- 1.1 pmol/L; P = .1) and VEGF in plasma increased from 34.3 +/- 37 to 92.2 +/- 86 pg/mL (P = .051). CONCLUSIONS: Patients undergoing conversion from CNI to sirolimus treatment for CAD presented a significant decrease in TGF-beta urine levels, representing a decreased mediator of the CAD fibrogenic process.

Association of Brain-Dead Donors' Terminal Inflammation With Delayed Graft Function in Kidney Transplant Recipients.

BACKGROUND: Systemic inflammation affects kidney function in a wide range of diseases. Even in kidney transplant recipients, higher levels of C-reactive protein (CRP) are invariably associated with both worse short- and long-term graft outcomes. However, little is known about systemic inflammation in kidney donors and, notably, brain death causes a strong systemic inflammatory response. OBJECTIVE: To analyze the role of systemic inflammation of brain-dead donors on short-term kidney graft outcomes (ie, delayed graft function [DGF], defined as the need of dialysis during the first week after transplantation). MATERIALS AND METHODS: Retrospective analysis of clinical and biochemical characteristics of all brain-dead kidney donors generated in the Hospital Clínic of Barcelona in the 2006 to 2015 period (n = 194). Donors who were tested for CRP in the 24 hours before BD declaration were included (n = 97, 50% of initial population). Clinical and biochemical features of their respective recipients (n = 165) were analyzed, comparing recipients who developed DGF (n = 30) with recipients who did not (n = 135). RESULTS: Donors whose recipients later developed DGF had much higher CRP values (10.58 [5.1-18.21] vs 4.81 [1.42-12.2] mg/dL, P = .025). Other characteristics associated with the development of DGF were renal biopsy score and recipient dialysis vintage (P = .025 and P = .002, respectively). In logistic regression analysis, PCR maintained significance in the non-expanded criteria donor (ECD) group (odds ratio [OR], 1.102; P = .027), but it lost significance in the ECD group (P = .67). CONCLUSIONS: Terminal donor CRP was associated with DGF in kidney transplant recipients and proved to be mostly significant in younger donors.

Inhibition of JAK3 and PKC via Immunosuppressive Drugs Tofacitinib and Sotrastaurin Inhibits Proliferation of Human B Lymphocytes In Vitro.

BACKGROUND: Antibody-mediated response in solid organ transplantation is critical for graft dysfunction and loss. The use of immunosuppressive agents partially inhibits the B-lymphocyte response leading to a risk of acute and chronic antibody-mediated rejection. This study evaluated the impact of JAK3 and PKC inhibitors tofacitinib (Tofa) and sotrastaurin (STN), respectively, on B-cell proliferation, apoptosis, and activation in vitro. METHODS: Human B cells isolated from peripheral blood of healthy volunteers were cocultured with CD40 ligand-transfected fibroblasts as feeder cells in the presence of interleukin (IL) 2, IL-10, and IL-21. The cocultures were treated with immunosuppressants Tofa, STN, and rapamycin (as a control), to analyze the proliferation and apoptosis of B cells by means of Cyquant and flow cytometry, respectively. CD27 and IgG staining were applied to evaluate whether treatments modified the activation of B cells. RESULTS: Tofa and STN were able to inhibit B-cell proliferation to the same extent as rapamycin, without inducing cell apoptosis. After 6 days in coculture with feeder cells, all B cells showed CD27 memory B-cell phenotype. None of the immunosuppressive treatments modified the proportion between class-switched and non-class-switched memory B cells observed in nontreated cultures. The high predominance of CD27+CD24+ phenotype was not modified by any immunosuppressive treatment. CONCLUSIONS: Our results show that Tofa and STN can suppress B-cell antibody responses to an extent similar to rapamycin, in vitro; therefore these compounds may be a useful therapy against antibody-mediated rejection in transplantation.

Evolution of proteinuria after conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) in renal transplant patients: a multicenter study.

Conversion from calcineurin inhibitors (CNI) to sirolimus (SRL) has become an option in patients with chronic allograft nephropathy or other conditions. However, in some cases an increase of proteinuria has been reported after such therapeutic intervention. The aim of this study was to characterize the clinical course of this so far unexplained proteinuria after conversion. We performed a retrospective analysis evaluating 94 renal transplant patients from various Spanish centers. Proteinuria (629 determinations) and clinical developments were analyzed between 6 months before and 6 months after conversion. Patients were divided into three groups according to mean proteinuria before conversion (group A: <300 mg/d; group B: 300 to 2000 mg/d; and group C: >2 g/d). The mean proteinuria level was 1.69 g/24 h (n = 312 determinations) before and 2.36 g/24 h after conversion (n = 317 determinations; P = .006), which corresponds to an overall increase of 25% (1.55 to 1.69 g/24 h considering only determinations of 1 month before and 1 month after conversion; P = NS). We could not detect any clear correlation between proteinuria and serum creatinine nor between changes of proteinuria and changes of serum creatinine. A variance analysis for repeated measures showed an increase in proteinuria compared to the preconversion values (P = .003), and when the three groups of preconversion proteinuria were evaluated separately it could be observed that this change in the evolution of proteinuria was almost completely dependent of an increase in the group C (preconversion proteinuria greater than 2 g/d; P = .03), whereas in the other two groups changes were almost irrelevant. Finally, the switch to SRL in renal transplant recipients is followed by an increase in the level of proteinuria predominantly dependent of an increase in patients with high levels of preconversion proteinuria, whereas it seems to be irrelevant in patients without or with light or moderate proteinuria. These results suggest that this might not be a direct effect of SRL.

Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats.

OBJECTIVE: The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. METHODS: We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. RESULTS: In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 +/- 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 +/- 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 +/- 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (-18.6 +/- 2.1 and -19 +/- 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+2.8 +/- 0.5 and +3.1 +/- 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY. CONCLUSIONS: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.