Publications by authors named "Bettina Jung"

29 Publications

  • Page 1 of 1

Sleep apnoea and incident malignancy in type 2 diabetes.

ERJ Open Res 2021 Apr 4;7(2). Epub 2021 May 4.

Dept of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.

Background: Sleep apnoea and type 2 diabetes (T2D) have been linked to malignancy. The aim of the present study was to evaluate the association between sleep apnoea and incidence of malignancy in patients with T2D.

Methods: The DIACORE (DIAbetes COhoRtE) study is a prospective, population-based cohort study in T2D patients. In the sleep disordered breathing substudy, the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and percentage of night-time spent with a peripheral oxygen saturation of <90% ( ) were assessed using a two-channel ambulatory monitoring device. Malignancy diagnoses were gathered using self-reported medical history data validated by medical records. Hazard ratios (HRs) for incident malignancy were derived by Cox regression adjusting for sex, age, body mass index, smoking status, alcohol intake, socioeconomic status and HbA1c.

Results: Of 1239 patients with T2D (mean age 67 years, 41% female, mean body mass index 30.9 kg·m), 79 (6.4%) were first-time diagnosed with a malignancy within a median follow-up period of 2.7 years (interquartile range 2.2-4.5 years). AHI, ODI and were not associated with incident malignancy. In subgroup analysis, females showed increased cancer risk per AHI unit (adjusted HR 1.03 per AHI unit, 95% CI 1.00-1.06; p=0.028) and severe sleep apnoea (defined as AHI ≥30 events·h; adjusted HR 4.19, 95% CI 1.39-12.77; p=0.012). This was not seen in males, and a significant interaction was observed (interaction terms p=0.048 and p=0.033, respectively).

Conclusion: Sleep apnoea was not associated with incident malignancy in T2D patients. However, stratified analysis revealed a significant association between sleep apnoea and incident malignancy in females, but not in males.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00036-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093486PMC
April 2021

Periodic breathing is associated with blood pressure above the recommended target in patients with type 2 diabetes.

Sleep Med X 2020 Dec 7;2:100013. Epub 2020 May 7.

Department of Internal Medicine II, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.

Background: Due to its prognostic importance for patients with type 2 diabetes (DM2), current guidelines recommend a systolic <130 mm Hg and diastolic <80 mm Hg blood pressure target. Periodic breathing, a form of sleep-disordered breathing, acutely causes repetitive hypoxia, sympathetic nervous system activation as well as oscillations of heart rate and blood pressure. However, limited data on the association of periodic breathing and control of blood pressure (BP) in patients with DM2 are available. Thus, the aim of the present study was to assess whether there is an association between periodic breathing and increased BP above the recommended target in DM2.

Methods: Cross-sectional data of 679 patients with DM2 from the DIACORE-SDB sub-study were analysed for association of periodic breathing with BP. Sleep-disordered breathing was assessed with a 2-channel ambulatory monitoring device including validated automatic pattern recognition for periodic breathing. BP values were determined in a standardized manner with three repeated measurements at rest.

Results: Of the 679 analysed individuals (61% male, age 66 ± 9 years, Body Mass Index [BMI] 31.0 ± 5.4 kg/m), 11% had periodic breathing. Patients with periodic breathing had significantly higher systolic BP values (144 ± 19 mm Hg vs. 137 ± 18 mm Hg, p = 0.003). Multivariable regression analysis revealed that periodic breathing was associated with higher systolic BP (B [95% confidence interval, CI] = 4.4 [0.1; 8.7], p = 0.043) and not meeting the recommended BP target for patients with diabetes (<130/80 mmHg) (odds ratio, OR [95%CI] = 2.1 [1.1; 4.0], p = 0.026) independent of sex, age, high density lipoproteins, renal function, coronary heart disease and antihypertensive treatment.

Conclusion: Periodic breathing is associated with higher systolic BP in patients with DM2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleepx.2020.100013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041113PMC
December 2020

Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline.

Kidney Int 2021 04 31;99(4):926-939. Epub 2020 Oct 31.

Division of Nephrology, University of Washington, Seattle, Washington, USA; Kidney Research Institute, University of Washington, Seattle, Washington, USA.

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m at follow-up among those with eGFRcrea 60 mL/min/1.73m or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.09.030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010357PMC
April 2021

Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

Nat Genet 2019 10 2;51(10):1459-1474. Epub 2019 Oct 2.

Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden.

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0504-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858555PMC
October 2019

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria.

Nat Commun 2019 09 11;10(1):4130. Epub 2019 Sep 11.

Department of Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT, USA.

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-11576-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739370PMC
September 2019

A catalog of genetic loci associated with kidney function from analyses of a million individuals.

Nat Genet 2019 06 31;51(6):957-972. Epub 2019 May 31.

Diabetes and Cardiovascular Disease-Genetic Epidemiology, Department of Clincial Sciences in Malmö, Lund University, Malmö, Sweden.

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0407-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698888PMC
June 2019

Poor risk factor control in outpatients with diabetes mellitus type 2 in Germany: The DIAbetes COhoRtE (DIACORE) study.

PLoS One 2019 21;14(3):e0213157. Epub 2019 Mar 21.

Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.

Introduction: Patients with diabetes mellitus type 2 (DM2) are at high risk for micro- and macrovascular disease. Here, we explore the degree of traditional risk factor control in the baseline visit of a cohort of DM2 outpatients.

Methods: DIACORE (DIAbetes COhoRtE) is a prospective cohort study of 3000 adult DM2 outpatients. Here, we present results from the baseline visit. Sociodemographic and anthropometric variables, cardiovascular risk factors, comorbidities and medication were assessed by interview and medical exams. Serum-creatinine based estimated glomerular filtration rate (eGFRcrea) and urinary albumin-creatinine ratio (UACR) were determined for classification of chronic kidney disease (CKD). The proportion of patients with adequate control of traditional risk factors (blood pressure<140/90mmHg, HbA1c<7.5%, LDL<100mg/dl) was calculated in 2892 patients with non-missing data in 9 relevant variables within each KDIGO 2012 CKD class.

Results: In the analyzed baseline data (n = 2892, 60.2% men), mean (standard deviation) values for age, DM2 duration and HbA1c were 65.3 (9.3) years, 10.3 (8.4) years and 6.9% (1.1) respectively. Of these 2892 patients, 18.7% had CKD stage 3 or higher, 25.7% had UACR≥30mg/g. Adequate blood pressure, HbA1c and LDL control was achieved in 55.7%, 78.5% and 34.4%, respectively. In 16.4% of patients (473), all three risk factors were below recommended targets. The proportion of adequate risk factor control was similar across KDIGO eGFRcrea classes. Adequate blood pressure and HbA1c control were significantly associated with lower UACR category without and with controlling for other risk factors (p<0.0001, p = 0.0002, respectively).

Conclusion: In our study of patients with diabetes mellitus type 2, we observed a low level of risk factor control indicating potential for risk reduction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213157PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428304PMC
December 2019

Daytime napping and diabetes-associated kidney disease.

Sleep Med 2019 02 25;54:205-212. Epub 2018 Nov 25.

Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany. Electronic address:

Background: Diabetes-associated Kidney Disease (DKD) is a common comorbidity in patients with type 2 diabetes. The present study investigates whether daytime sleeping duration in patients, ill with type 2 diabetes, is associated with DKD.

Methods: A total of 733 outpatients of the cross-sectional baseline survey of the DIACORE study were analyzed with respect to their self-reported daytime sleeping duration, assessed by a standardized questionnaire. DKD was defined as eGFR <60 ml/min/1.73 m and/or urinary albumin-to-creatinine-ratio (UACR) > 30 mg/g.

Results: Mean daytime sleeping duration was 17 ± 27 min. With increasing daytime sleeping duration a statistically significant decrease in eGFR (p = 0.002) and increase in UACR (p < 0.001) were found, respectively. Prevalence of DKD was significantly higher in patients with longer daytime sleeping duration (31% in patients not napping, 40% in patients napping less than 30 min, 47% in patients napping 30-60 min, 56% in patients napping 60 min or more; p = 0.001). After accounting for known modulators (Age, sex, BMI, waist-hip-ratio, systolic and diastolic blood pressure, physical activity, diabetes duration, HbA1c, homeostasis model assessment (HOMA-Index), nighttime sleeping duration, apnea-hypopnea-index (AHI), Epworth Sleepiness Scale (ESS)), longer daytime sleeping duration was significantly associated with impaired eGFR [B (95% CI) = -0.05 (-0.09; 0.00), p = 0.044] and increased UACR [B (95% CI) = 0.01 (0.01; 0.02), p < 0.001], respectively.

Conclusion: Increased daytime sleeping duration is significantly associated with reduced eGFR and higher UACR, independent of known modulators of DKD. The direction of this relationship remains unclear.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2018.10.034DOI Listing
February 2019

Excessive dietary lipid intake provokes an acquired form of lysosomal lipid storage disease in the kidney.

J Pathol 2018 12 5;246(4):470-484. Epub 2018 Nov 5.

Pathology Department, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

Obesity and dyslipidaemia are features of the metabolic syndrome and risk factors for chronic kidney disease. The cellular mechanisms connecting metabolic syndrome with chronic kidney disease onset and progression remain largely unclear. We show that proximal tubular epithelium is a target site for lipid deposition upon overnutrition with a cholesterol-rich Western-type diet. Affected proximal tubule epithelial cells displayed giant vacuoles of lysosomal or autophagosomal origin, harbouring oxidised lipoproteins and concentric membrane layer structures (multilamellar bodies), reminiscent of lysosomal storage diseases. Additionally, lipidomic analysis revealed renal deposition of cholesterol and phospholipids, including lysosomal phospholipids. Proteomic profiles of renal multilamellar bodies were distinct from those of epidermis or lung multilamellar bodies and of cytoplasmic lipid droplets. Tubular multilamellar bodies were observed in kidney biopsies of obese hypercholesterolaemic patients, and the concentration of the phospholipidosis marker di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate was doubled in urine from individuals with metabolic syndrome and chronic kidney disease. The enrichment of proximal tubule epithelial cells with phospholipids and multilamellar bodies was accompanied by enhanced inflammation, fibrosis, tubular damage markers, and higher urinary electrolyte content. Concomitantly to the intralysosomal lipid storage, a renal transcriptional response was initiated to enhance lysosomal degradation and lipid synthesis. In cultured proximal tubule epithelial cells, inhibition of cholesterol efflux transport or oxysterol treatment induced effects very similar to the in vivo situation, such as multilamellar body and phospholipid amassing, and induction of damage, inflammatory, fibrotic, and lipogenic molecules. The onset of phospholipidosis in proximal tubule epithelial cells is a novel pathological trait in metabolic syndrome-related chronic kidney disease, and emphasises the importance of healthy lysosomes and nutrition for kidney well-being. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/path.5150DOI Listing
December 2018

Association of sleep-disordered breathing with severe chronic vascular disease in patients with type 2 diabetes.

Sleep Med 2018 08 14;48:53-60. Epub 2018 May 14.

Department of Internal Medicine II, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. Electronic address:

Background: Severe chronic vascular disease (CVD) is a major cause of co-morbidity and mortality in patients with type 2 diabetes (DM2). Sleep-disordered breathing (SDB) has been linked to CVD in the general population due to enhanced sympathetic activation, oxidative stress, endothelial dysfunction, and hypertension; however data for DM2 patients is scarce. Therefore, the aim of the present analysis to assess whether SDB is associated with CVD in patients with DM2, independent of other known associated factors.

Methods: We analyzed cross-sectional data of 679 patients with DM2 from the DIACORE-SDB sub-study for association of SDB with CVD. SDB was assessed with a validated 2-channel ambulatory monitoring device. CVD was ascertained as a previous diagnosis of peripheral artery disease (PAD), coronary artery disease (CAD), or stroke via medical records and general practitioners.

Results: Of the analyzed 679 patients, 228 (34%) had SDB (respiratory event index [REI] ≥15/hour); and were significantly more often affected by CVD than patients without SDB (38% vs. 23%, p < 0.01; PAD 7% vs. 2%, p = 0.01; CAD 27% vs. 18%, p = 0.01; stroke 11% vs. 6%, p = 0.07). Regression analysis accounting for known modulators of CVD, such as age, body-mass index, systolic blood pressure, duration of DM2, HbA1c, smoking status, and low-density lipoprotein showed that the REI was independently associated with CVD (OR 1.099 per 5 REI points; 95%CI = [1.024, 1.179]).

Conclusions: In patients with DM2, SDB is significantly associated with CVD, independent of other known modulators of atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.sleep.2018.05.001DOI Listing
August 2018

Analysis of Luminex-based Algorithms to Define Unacceptable HLA Antibodies in CDC-crossmatch Negative Kidney Transplant Recipients.

Transplantation 2018 06;102(6):969-977

Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.

Background: HLA-specific antibodies detected by solid phase assays are increasingly used to define unacceptable HLA antigen mismatches (UAM) before renal transplantation. The accuracy of this approach is unclear.

Methods: Day of transplant sera from 211 complement-dependent cytotoxicity crossmatch-negative patients were retrospectively analyzed for donor-specific anti-HLA antibodies (DSA) using Luminex technology. HLA were defined as UAM if DSA had mean fluorescence intensity above (I) 3000 (patients retransplanted and those with DSA against HLA class I and II) or 5000 (all other patients), (II) 5000 for HLA-A, -B, and -DR and 10 000 for HLA DQ or (III) 10 000 (all HLA). We then studied the accuracy of these algorithms to identify patients with antibody-mediated rejection (AMR) and graft loss. UAM were also determined in 256 transplant candidates and vPRA levels calculated.

Results: At transplantation, 67 of 211 patients had DSA. Of these, 31 (algorithm I), 24 (II) and 17 (III) had UAM. Nine (I and II) and 8 (III) of 11 early AMR episodes and 7 (I), 6 (II) and 5 (III) of 9 graft losses occurred in UAM-positive patients during 4.9 years of follow-up. Algorithms I and II identified patients with persistently lower glomerular filtration rate even in the absence of overt AMR. Of the waiting list patients, 22-33% had UAM with median virtual panel reactive antibody of 69.2% to 79.1%.

Conclusions: Algorithms I and II had comparable efficacy but were superior to Algorithm III in identifying at-risk patients at an acceptable false-positive rate. However, Luminex-defined UAM significantly restrict the donor pool of affected patients, which might prolong waiting time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000002129DOI Listing
June 2018

Renal allograft rejection, lymphocyte infiltration, and de novo donor-specific antibodies in a novel model of non-adherence to immunosuppressive therapy.

BMC Immunol 2017 Dec 19;18(1):52. Epub 2017 Dec 19.

Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauß Allee 11, D-93053, Regensburg, Germany.

Background: Non-adherence has been associated with reduced graft survival. The aim of this study was to investigate the immunological mechanisms underlying chronic renal allograft rejection using a model of non-adherence to immunosuppressive therapy. We used a MHC (major histocompatibility complex) -mismatched rat model of renal transplantation (Brown Norway to Lewis), in which rats received daily oral cyclosporine A. In analogy to non-adherence to therapy, one group received cyclosporine A on alternating days only. Rejection was histologically graded according to the Banff classification. We quantified fibrosis by trichrome staining and intra-graft infiltration of T cells, B cells, and monocytes/macrophages by immunohistochemistry. The distribution of B lymphocytes was assessed using immunofluorescence microscopy. Intra-graft chemokine, chemokine receptor, BAFF (B cell activating factor belonging to the TNF family), and immunoglobulin G transcription levels were analysed by RT-PCR. Finally, we evaluated donor-specific antibodies (DSA) and complement-dependent cytotoxicity using flow cytometry.

Results: After 28 days, cellular rejection occurred during non-adherence in 5/6 animals, mixed with humoral rejection in 3/6 animals. After non-adherence, the number of T lymphocytes were elevated compared to daily immunosuppression. Monocyte numbers declined over time. Accordingly, lymphocyte chemokine transcription was significantly increased in the graft, as was the transcription of BAFF, BAFF receptor, and Immunoglobulin G. Donor specific antibodies were elevated in non-adherence, but did not induce complement-dependent cytotoxicity.

Conclusion: Cellular and humoral rejection, lymphocyte infiltration, and de novo DSA are induced in this model of non-adherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12865-017-0236-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735914PMC
December 2017

Biomarker-guided Intervention to Prevent Acute Kidney Injury After Major Surgery: The Prospective Randomized BigpAK Study.

Ann Surg 2018 06;267(6):1013-1020

Department of Nephrology, University Hospital Regensburg, Germany.

Objective: To determine the impact of renal biomarker-guided implementation of the Kidney Disease Improving Global Outcomes (KDIGO) care bundle on the incidence of acute kidney injury (AKI) after major noncardiac surgery in a single-center unblinded randomized clinical trial.

Background: Early optimization of volume status and discontinuation of nephrotoxic medication before the occurrence of AKI may be the crucial step to reduce preventable AKI.

Methods: The urinary biomarker-triggered KDIGO care bundle (early optimization of fluid status, maintenance of perfusion pressure, discontinuation of nephrotoxic agents) was compared to standard intensive care unit (ICU) care in 121 patients with an increased AKI risk after major abdominal surgery that was determined by urinary biomarker (inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7) >0.3. Incidence of overall AKI, severity of AKI, length of stay, major kidney events at discharge, and cost effectiveness were evaluated.

Results: The overall stages of AKI were not statistically different between the 2 groups, but in patients with inhibitor of metalloproteinase-2 × insulin-like growth factor-binding protein 7 values of 0.3 to 2.0 a subgroup analysis demonstrated a significantly reduced incidence of AKI 13/48 (27.1%) in the intervention group compared to control 24/50 (48.0%, P = 0.03). Incidence of moderate and severe AKI (P = 0.04), incidence of creatinine increase >25% of baseline value (P = 0.01), length of ICU, and hospital stay (P = 0.04) were significantly lower in the intervention group. Intervention was associated with cost reduction. There were no significant differences regarding renal replacement therapy, in-hospital mortality, or major kidney events at hospital discharge.

Conclusions: Early biomarker-based prediction of imminent AKI followed by implementation of KDIGO care bundle reduced AKI severity, postoperative creatinine increase, length of ICU, and hospital stay in patients after major noncardiac surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0000000000002485DOI Listing
June 2018

Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

PLoS One 2016 10;11(6):e0156900. Epub 2016 Jun 10.

Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.

Objective: Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation.

Results: Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival.

Conclusion: The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust relationship between macrophage infiltration, accompanying antigen-presentation and resulting allograft function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156900PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902310PMC
July 2017

Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.

Transpl Immunol 2013 Jan 23;28(1):24-31. Epub 2012 Dec 23.

Department of Internal Medicine II, University Medical Center Regensburg, Franz-Joseph-Strauss-Allee 11, 93042 Regensburg, Germany.

The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs. Data were correlated with the corresponding kidney function as well as with histopathological classification. The information provided by the morphometric software programs on the infiltration of the specific cell types after renal transplantation was in accordance with the manual analysis. Morphometric methods were solid to analyze reliably the induction of cellular infiltrates after renal transplantation. By manual analysis we could clearly demonstrate the detailed localization of the specific cell infiltrates in the different kidney compartments. Besides infiltration of CD3 and CD68 infiltrating cells, a robust infiltration of CD20 B-cells in allogeneically transplanted rats, even at early time points after transplantation was detected. Additionally an MHC class I expression could reliable be seen in allogeneically transplanted rats. The infiltration of B-cells and the reliable antigen presentation might act as a silent subclinical trigger for subsequent chronic rejection and premature graft loss.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trim.2012.12.001DOI Listing
January 2013

Toll-like receptor 4 in experimental kidney transplantation: early mediator of endogenous danger signals.

Nephron Exp Nephrol 2012 21;121(3-4):e59-70. Epub 2012 Nov 21.

Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.

The role of toll-like receptors (TLRs) has been described in the pathogenesis of renal ischemia/reperfusion injury, but data on the expression and function of TLR4 during renal allograft damage are still scarce. We analyzed the expression of TLR4 in an experimental rat model 6 and 28 days after allogeneic kidney transplantation in comparison to control rats and rats after syngeneic transplantation. On day 6, a significant induction in TLR4 expression--restricted to the glomerular compartment--was found in acute rejecting allografts only. TLR4 expression strongly correlated with renal function, and TLR4 induction was accompanied by a significant increase in CC chemokine expression within the graft as well as in urinary CC chemokine excretion. TLR4 induction may be caused by an influx of macrophages as well as TLR4-expressing intrinsic renal cells. Fibrinogen deposition in renal allografts correlated with renal TLR4 expression and may act as a potent stimulator of chemokine release via TLR4 activation. This study provides, for the first time, data about the precise intrarenal localization and TLR4 induction after experimental kidney transplantation. It supports the hypothesis that local TLR4 activation by endogenous ligands may be one pathological link from unspecific primary allograft damage to subsequent chemokine release, infiltration and activation of immune cells leading to deterioration of renal function and induction of renal fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000343566DOI Listing
December 2013

Traditional and nontraditional cardiovascular risk factors and estimated risk for coronary artery disease in renal transplant recipients: a single-center experience.

Nephron Clin Pract 2011 18;119(3):c227-35. Epub 2011 Aug 18.

Klinik und Poliklinik für Innere Medizin II, Nephrologie, University of Regensburg, Regensburg, Germany.

Background/aims: The prevalence of cardiovascular disease in renal transplant recipients is markedly higher than in the general population due to the high prevalence of traditional cardiovascular risk factors, renal transplant function impairment and treatment with immunosuppressive drugs that affect blood pressure, cholesterol and blood glucose levels.

Methods: Cross-sectional analysis using our renal transplant clinic cohort investigating (1) the cardiovascular risk factors present in this cohort, and (2) estimating their impact on the risk of coronary artery disease (CAD) by using the Framingham algorithm.

Results: Control of modifiable cardiovascular risk factors in 231 renal transplant recipients is suboptimal, i.e. 47.2% of patients are hypertensive, 10.3% actively smoke, 39.4% have serum cholesterol concentrations >200 mg/dl, and 19.7% have diabetes mellitus. Blood pressure, age, hyperlipidemia, smoking and diabetes modulate the estimated CAD risk in males and females. Furthermore, a short time period (less than 1 year) since transplantation and increased serum creatinine levels negatively influenced the CAD risk in this patient population.

Conclusion: According to current guidelines, the control of modifiable cardiovascular risk factors in renal transplant recipients is suboptimal. The decreasing CAD risk over time after transplantation may be due to the reduction of immunosuppressive drugs with time and survival bias.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000327616DOI Listing
April 2012

Kidney injury molecule-1 and N-acetyl-β-D-glucosaminidase in chronic heart failure: possible biomarkers of cardiorenal syndrome.

Eur J Heart Fail 2011 Oct 16;13(10):1104-10. Epub 2011 Aug 16.

Departments of Cardiology and Nephrology, Klinik und Poliklinik fuer Innere Medizin II, Universitätsklinikum Regensburg, Regensburg, Germany.

Aims: Patients with chronic heart failure are often characterized by impaired renal function, also referred to as cardiorenal syndrome (CRS). The aim of this study was to assess whether novel markers of kidney injury are elevated in chronic heart failure and CRS.

Methods And Results: The new renal biomarkers kidney injury molecule-1 (KIM-1), N-acetyl-ß-d-glucosaminidase (NAG) and neutrophil gelatinase-associated lipocalin (NGAL) were assessed from urine samples of 173 individuals. Patients with chronic heart failure (n= 150) were characterized by decreased ejection fraction (32 ± 9% vs. controls 62 ± 4%, P < 0.001) and increased plasma N-terminal pro-brain natriuretic peptide (median 1460 pg/mL, interquartile range (IQR) 630-3000 pg/mL vs. controls 56, IQR 25-64l pg/mL, P < 0.001). Urinary analysis showed that KIM-1 was significantly elevated in heart failure patients compared with healthy controls (1100, IQR 620-1920 vs. 550, IQR 320-740 ng/g urinary creatinine, P < 0.001). Further, KIM-1 increased significantly with decreasing left ventricular function (r = -0.37, P < 0.001) and severity of New York Heart Association (NYHA)-class (r = 0.5, P < 0.001). N-acetyl-ß-d-glucosaminidase showed a weaker response but correlated significantly with left ventricular dysfunction (r = -0.18, P= 0.015) and more severe clinical condition (r = 0.22, P= 0.04). In contrast, NGAL showed no significant correlation. Kidney injury molecule-1 and NAG were also predictors of all-cause mortality and the composite of all-cause mortality and rehospitalization for heart failure (all P < 0.05).

Conclusions: Kidney injury molecule-1 and NAG are elevated in symptomatic heart failure. This finding may be present in patients with apparently normal kidney function and indicates tubular injury in chronic heart failure. Kidney injury molecule-1 and NAG are potential markers of CRS with additional prognostic value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurjhf/hfr102DOI Listing
October 2011

Hypertonic stress promotes the upregulation and phosphorylation of zonula occludens 1.

Nephron Physiol 2011 7;119(2):p11-21. Epub 2011 Jul 7.

Department of Internal Medicine II, University Medical Center, Regensburg, Germany.

Tight junction molecules form a barrier between adjacent cells and mediate the cells' ability to develop membranes that constitute boundaries of different compartments within the body. Membranes with selective ion and water passage are important for the electrolyte and water homeostasis in the kidney. Due to their role in the urinary concentration process, renal medullary cells are exposed to hyperosmotic stress. Therefore, we were interested in the question of how mouse inner medullary collecting duct cells (mIMCD3) manage to maintain their cell-cell contacts, despite hypertonicity-induced cell shrinkage. Employing mRNA expression analysis, we found that the zonula occludens type 1 (Zo-1), multi-PDZ domain protein 1 (MUPP1) and cortactin mRNA levels were upregulated in a tonicity-dependent manner. Using Western blot analysis, immunoprecipitation and immunofluorescence, we show that the Zo-1 protein is upregulated, phosphorylated and linked to the actin cytoskeleton in response to hypertonic stress. After cell exposure to hypertonicity, rearrangement of the actin cytoskeleton resulted in a stronger colocalization of actin fibres with Zo-1. Urea, which generates hyperosmolality, but no transcellular gradient, did not induce changes in Zo-1 protein expression or actin rearrangement. This data indicates that Zo-1 is a response protein to inner medullary tonicity and that extracellular stressors can promote Zo-1 protein expression, tyrosine phosphorylation and cytoskeleton association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000327567DOI Listing
February 2012

Impact of Toll-like receptor 2 expression in renal allograft rejection.

Nephrol Dial Transplant 2011 Mar 13;26(3):1080-7. Epub 2010 Jul 13.

Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, Germany.

Background: An important role of TLR2 has been shown in various experimental models of renal ischaemia/reperfusion injury. To study the expression of TLR2 in renal allograft rejection systematically, we established an experimental rat transplantation model.

Methods: TLR2 expression was analysed in 99 human renal allograft biopsies, and in rat allografts at Day 6 and 28 after experimental renal transplantation. To discriminate whether regulation of TLR2 was following immunological processes after allogeneic transplantation or was a consequence from ischaemia/reperfusion injury, control animals subjected to syngeneic transplantation or to ischaemia/reperfusion damage were also investigated.

Results: TLR2 mRNA was significantly elevated in rat allografts with acute rejection on Day 6 and decreased spontaneously towards Day 28. TLR2 induction correlated with renal function and TLR2 excretion in the urine of transplanted rats. TLR2 staining was also significantly increased in human allografts with acute rejection. TLR2 protein could be localized in tubular epithelial cells and vascular endothelial cells, and in CD68- and CD4-positive infiltrating cells.

Conclusions: TLR2 is markedly up-regulated in both experimental and human acute renal allograft rejection. Our data suggest a role for TLR2 during allogen-dependent graft damage after renal transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfq420DOI Listing
March 2011

Synthesis and pharmacological evaluation of SNC80 analogues with a bridged piperazine ring.

ChemMedChem 2009 Dec;4(12):2111-22

Institut für Pharmazeutische und Medizinische Chemie, Universität Münster, Hittorfstrasse 58-62, 48149 Münster, Germany.

To discover novel delta-opioid receptor ligands derived from SNC80 (1), a series of 6,8-diazabicyclo[3.2.2]nonane derivatives bearing two aromatic moieties was prepared, and the affinity toward delta, mu, and kappa receptors, as well as sigma receptors, was investigated. After removal of the 4-methoxybenzyl and 2,4-dimethoxybenzyl protecting groups, the pharmacophoric N,N-diethylcarbamoylbenzyl residue was attached to the 6,8-diazabicyclo[3.2.2]nonane framework to yield the designed delta receptor ligands. In a first series of compounds the benzhydryl moiety of SNC80 was dissected, and one phenyl ring was attached to the bicyclic framework. In a second series of delta ligands the complete benzhydryl moiety was introduced into the bicyclic scaffold. The determined delta receptor affinities show that compounds based on an (R)-glutamate-derived bicyclic scaffold possess higher delta receptor affinity than their (S)-glutamate-derived counterparts. Furthermore, an intact benzhydryl moiety leads to delta receptor ligands that are more potent than compounds with two separated aromatic moieties. Compound 24, with the same spatial arrangement of substituents around the benzhydryl stereocenter as SNC80, shows the highest delta receptor affinity of this series: K(i)=24 nM. Whereas the highly potent delta ligands reveal good selectivity against mu and kappa receptors, the sigma(1) and/or sigma(2) affinities of some compounds are almost in the same range as their delta receptor affinities, such as compound 25 (sigma(2): K(i)=83 nM; delta: K(i)=75 nM). In [(35)S]GTPgammaS assays the most potent delta ligands 24 and 25 showed almost the same intrinsic activity as the full agonist SNC80, proving the agonistic activity of 24 and 25. The enantiomeric 4-benzylidene derivatives 15 and ent-15 showed selective cytotoxicity toward the 5637 (bladder) and A-427 (small-cell lung) human tumor cell lines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cmdc.200900358DOI Listing
December 2009

Reduced exposure to calcineurin inhibitors in renal transplantation.

N Engl J Med 2008 Jun;358(23):2519; author reply 2519-20

View Article and Find Full Text PDF

Download full-text PDF

Source
June 2008

Synthesis and pharmacological evaluation of bicyclic SNC80 analogues with separated benzhydryl moiety.

Bioorg Med Chem 2008 Mar 10;16(6):2870-85. Epub 2008 Jan 10.

Institut für Pharmazeutische und Medizinische Chemie, Westfälische Wilhelms-Universität, D-48149 Münster, Germany.

Directed by molecular modeling studies the pharmacophoric benzhydryl moiety of the delta opioid receptor agonist SNC80 was separated and the two phenyl residues were attached to different positions of the conformationally constrained 6,8-diazabicyclo[3.2.2]nonane framework in order to find novel delta agonists. The crucial reaction step in the chiral pool synthesis was the establishment of the three carbon bridge by a Dieckmann analogous cyclization of the allyl and propyl derivatives 6 and 7 to yield the mixed methyl silyl acetals 8 and 9, respectively. Stereoselective Grignard reaction, dehydration, and introduction of the pharmacophoric (N,N-diethylcarbamoylbenzyl) residue led to the designed delta receptor agonists 3, ent-3, and 20 with a double bond in the bicyclic framework. Hydrogenation of the allyl derivative 14 was performed with ammonium formate and Pd/C to yield the saturated ligands 24a and 24b. Removal of the allyl substituent with RhCl(3), hydrogenation of the ring system, and re-attachment of the allyl moiety provided the allyl derivatives 4a and 4b. In receptor binding studies with the radioligand [(3)H]-deltorphine II only ent-3 showed considerable delta receptor affinity (K(i)=740 nM). Since ent-3 also interacts with mu receptors (K(i)=250 nM) it belongs to the very interesting compound class of mixed delta/mu ligands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmc.2008.01.004DOI Listing
March 2008

Autoimmunity as a result of escape from RNA surveillance.

J Immunol 2006 Aug;177(3):1698-707

Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

In previous studies, we detected a frame shift mutation in the gene encoding the autoantigen La of a patient with systemic lupus erythematosus. The mutant La mRNA contains a premature termination codon. mRNAs that prematurely terminate translation should be eliminated by RNA quality control mechanisms. As we find Abs specific for the mutant La form in approximately 30% of sera from anti-La-positive patients, we expected that mutant La mRNAs circumvent RNA control and the expression of mutant La protein could become harmful. Indeed, real-time PCR, immunostaining, and immunoblotting data of mice transgenic for the mutant La form show that mutant La mRNAs are not repressed in these animals and are translated to mutant La protein. In addition to the mutant La protein, we detected a minor portion of native human La in the mutant La-transgenic mice. Therefore, ribosomal frame shifting may allow the mutant La mRNA to escape from RNA control. Interestingly, expression of the mutant La mRNA results in a lupus-like disease in the experimental mice. Consequently, escape of mutant La mRNA from RNA control can have two effects: it 1) results in the expression of an immunogenic (neo)epitope, and 2) predisposes to autoimmunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2206679PMC
http://dx.doi.org/10.4049/jimmunol.177.3.1698DOI Listing
August 2006

Molecular modeling directed synthesis of a bicyclic analogue of the delta opioid receptor agonist SNC 80.

Arch Pharm (Weinheim) 2005 Jun;338(5-6):281-90

Institut für Pharmazeutische und Medizinische Chemie, Münster, Germany.

In order to find novel delta opioid receptor agonists, the pharmacophoric benzhydryl moiety of the lead compound SNC 80 (1) was dissected and the phenyl residues were attached to different positions of the 6,8-diazabicyclo[3.2.2]nonane core system (4). The position of the carboxamido group, the stereochemistry, the C3/C4 bond order and the kind and length of the spacer X were considered. The resulting compounds were compared with the four energetically most favourable conformations of SNC 80 by a multifit analysis. These calculations led to the structures 5-10, which fit best to SNC 80. Herein the synthesis of one of these compounds (9) is described. Starting from (S)-glutamate two alternative routes are detailed to obtain the key intermediate 14. A variation of the Dieckmann cyclization, which uses trapping of the first cyclization product with ClSiMe(3) provided the mixed acetal 20, which was carefully hydrolyzed to yield the bicyclic ketone 17. Stereoselective addition of phenylmagnesium bromide, dehydration, LiAlH(4) reduction and exchange of the N-6 residue afforded the designed compound 9. The affinities of 9 towards delta, mu, kappa and ORL1 receptors were determined in receptor binding studies with radioligands. Only moderate receptor affinity was found.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.200400994DOI Listing
June 2005

Is postcontrast trueFISP imaging advantageous?

Invest Radiol 2004 Sep;39(9):517-23

Department of Diagnostic Radiology, University of Technology, Aachen, Germany.

Rationale And Objectives: Contrast of trueFISP images depends mainly on the T2/T1 ratio. Consequently, there is a potential gain in signal intensity after administration of paramagnetic contrast medium despite the strong T2 weighting. The purpose of this study was to analyze signal intensities of abdominal organs after applying contrast medium and to determine whether this yields an improved contrast for pathologies compared with precontrast trueFISP.

Materials And Methods: Fifty patients underwent an abdominal examination, including the trueFISP sequence before and after the administration of contrast medium. All images were obtained with a 1.5 T system. The mean signal-to-noise ratio before and after contrast medium was assessed for abdominal organs, vessels, muscle, and fat. The contrast-to-noise ratio (CNR) of pathologic lesions was calculated.

Results: The trueFISP sequence yielded a higher signal-to-noise ratio after application of contrast medium for all organs except for fat and the aorta. CNR of solid lesions (angiomyolipoma, liver adenoma, liver hemangioma, hepatocellular carcinoma) increased whereas contrast of cysts decreased.

Conclusions: TrueFISP imaging after application of contrast medium led to better CNR for many solid lesions while cysts showed a diminished contrast. We advise trueFISP imaging sequences before and after contrast medium application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.rli.0000131476.52176.44DOI Listing
September 2004

A new algorithm for metal artifact reduction in computed tomography: in vitro and in vivo evaluation after total hip replacement.

Invest Radiol 2003 Dec;38(12):769-75

Department of Diagnostic Radiology, Aachen University of Technology, Germany.

Rationale And Objectives: To evaluate a newly developed algorithm for metal artifact reduction (MAR) in Computed Tomography (CT).

Methods: A projection interpolation algorithm for MAR with threshold-based metal segmentation was developed. First, the algorithm was tested with a simulated hip phantom. On demand, the presence of metallic inserts was simulated, representing total hip endoprostheses. Second, CT data of 20 patient with total hip endoprosthesis were reconstructed with and without application of the MAR algorithm. Image quality was independently assessed by 2 experienced radiologists using a qualitative score. The results of the in vitro study were evaluated with the Student's t test. Results of the in vivo study were analyzed using a repeated-measure analysis of variance.

Results: Applying the MAR algorithm the phantom study showed no significant difference between images with and without simulated metal contributions. The patient study revealed improved image quality using the MAR algorithm. Results were statistically significant for fat (P=0.0097), vessels (P=0.0091), and bone (P=0.0005). Improvement of the image quality for muscle was not statistically significant (P=0.0287).

Conclusions: A new algorithm for metal artifact reduction was successfully introduced into clinical routine. The algorithm led to a robust reduction of metal artifacts. The MAR algorithm may serve for an improvement in image quality in patients with metallic implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.rli.0000086495.96457.54DOI Listing
December 2003

Measurement of cardiac output from a test-bolus injection in multislice computed tomography.

Eur Radiol 2003 Nov 6;13(11):2498-504. Epub 2003 Aug 6.

Department of Radiology, University Hospital, Aachen University of Technology, Pauwelsstrasse 52, 52074, Aachen, Germany.

The aim of this study was to assess the feasibility of non-invasive determination of cardiac function from test-bolus data in multislice spiral computed tomography (MSCT). In 25 patients enhancement data gathered from a standardized test-bolus injection were analyzed. The test-bolus examination was performed prior to a retrospectively ECG-gated MSCT of the heart. A time-attenuation curve was obtained in the ascending aorta at the level of the pulmonary arteries. A gamma variate fit was applied to the curve in order to exclude recirculation and get pure first-pass data. Using the known amount of iodine injected, cardiac output (CO), and stroke volume (SV) were determined from integration of the fitted contrast enhancement curve using a reformation of the Stewart-Hamilton equation. Results were compared with CO and SV calculated from the geometric analysis of the retrospectively gated MSCT data using the ARGUS Software (Siemens, Forchheim, Germany). The CO and SV determined from test-bolus analysis and from geometric analysis correlated well with Pearson's correlation coefficients of 0.87 and 0.88, respectively. The standard deviation of the difference between both methods was 0.51 l/min for CO (8.6%) and 11.0 ml for SV (12.3%). Non-invasive quantification of CO seems to be feasible from a standard test-bolus injection. It provides valuable information on cardiac function without additional radiation or application of contrast material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-003-2054-xDOI Listing
November 2003

[An unusual cause of pulmonary fibrosis in a 71-year-old patient].

Med Klin (Munich) 2002 Mar;97(3):165-9

Case Report: A 71-year-old woman, suffering from spinal stenosis presented interstitial lung disease, albinism, and severe loss of visual acuity. On physical examination she showed tic-like automatism predominantly periorbital in the face and in the fingers. A computed tomography of the chest revealed typical findings of interstitial lung disease and additional mediastinal lymphomas and ground-glass attenuation in the lower regions of the lung. The findings of a transbronchial lung biopsy, presenting alveolar macrophages with ceroid-like material and platelet function studies proving slightly impaired platelet aggregation confirmed the clinical diagnosis of Hermansky-Pudlak syndrome. Sufficient pain control could be achieved without surgery and the patient was discharged home. 11 months after discharge, severe dyspnea and fever developed and finally the patient died of respiratory failure.

Conclusion: The Hermansky-Pudlak syndrome is a rare cause of interstitial lung disease. In general, the lung disease presents in younger patients, but it may emerge in the elderly as well. Alveolar macrophages containing ceroid-like material are typical findings in BAL or lung biopsy. Furthermore impaired platelet aggregation and bleeding diathesis may be present. Both findings are useful to identify this rare disorder.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00063-002-1141-0DOI Listing
March 2002
-->