SARS-CoV-2 seroprevalence and determinants of infection in young adults: a population-based seroepidemiological study.

OBJECTIVES: Most SARS-CoV-2 seroprevalence studies have focussed on adults and high-risk populations, and little is known about young adults. The objective of the present study was to provide evidence on the SARS-CoV-2 seroprevalence among young adults in Germany and to explore determinants associated with seropositivity in general and, specifically, with previously undetected infections. STUDY DESIGN: This was a population-based SARS-CoV-2 seroprevalence study. METHODS: In November 2020, a population-based study on SARS-CoV-2 seroprevalence in young adults (aged 18-30 years) was conducted in a large German city. Serum samples were obtained to analyse the SARS-CoV-2 antibody status using the Elecsys Anti-SARS-CoV-2 immunoassay. Descriptive statistics and odds ratios (ORs) of seropositivity and of previously undetected infections in relation to different determinants were calculated. RESULTS: Among 2186 participants, SARS-CoV-2 antibodies were detected in 72 individuals, equalling a test performance-adjusted seroprevalence of 3.1% (95% confidence interval [CI]: 2.4-4.0). Based on reported COVID-19 cases to the public health authority, a moderate underascertainment rate of 1.7 was calculated. Seropositivity was higher among individuals who sought COVID-19-related information from social media (OR: 1.83, 95% CI: 1.2-3.1), and undetected COVID-19 infections were more prevalent among men and those not adhering to social distancing. CONCLUSIONS: The results show a substantial underascertainment of SARS-CoV-2 infections among young adults and indicate that seroprevalence is likely to be much higher than the reported COVID-19 prevalence based on confirmed COVID-19 cases in Germany. Preventive efforts should consider the heterogeneity of risk profiles among the young adult population.

Underascertainment of COVID-19 cases among first responders: a seroepidemiological study.

BACKGROUND: Providing frontline support places first responders at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIMS: This study was aimed to determine the anti-SARS-CoV-2 seroprevalence in a cohort of first responders (i.e. firefighters/paramedics), to detect the underascertainment rate and to assess risk factors associated with seropositivity. METHODS: We conducted a serological survey among 745 first responders in Germany during 27 November and 4 December 2020 to determine the anti-SARS-CoV-2 seroprevalence using Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Mannheim, Germany). As part of the examination, participants were asked to provide information on coronavirus disease 2019 (COVID-19)-like-symptoms, information on sociodemographic characteristics and workplace risk factors for a SARS-CoV-2 infection and any prior COVID-19 infection. Descriptive statistics and logistic regression analysis were performed and seroprevalence estimates were adjusted for test sensitivity and specificity. RESULTS: The test-adjusted seroprevalence was 4% (95% CI 3.1-6.2) and the underascertainment rate was 2.3. Of those tested SARS-CoV-2 antibody positive, 41% were aware that they had been infected in the past. Seropositivity was elevated among paramedics who worked in the emergency rescue team providing first level of pre-hospital emergency care (6% [95% CI 3.4-8.6]) and those directly exposed to a COVID-19 case (5% [95% CI 3.5-8.1]). Overall, the seroprevalence and the underascertainment rate were higher among first responders than among the general population. CONCLUSIONS: The high seroprevalence and underascertainment rate highlight the need to mitigate potential transmission within and between first responders and patients. Workplace control measures such as increased and regular COVID-19-testing and the prompt vaccination of all personnel are necessary.

Prognostic value of the coronary artery calcium score in suspected coronary artery disease: a study of 644 symptomatic patients.

AIM: The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. METHODS: We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. RESULTS: The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8­year survival was 95% with CAC score <100, 90% in patients with CAC score >100 and <400, and 82% with CAC score ≥400 Agatston units. Risk of mortality with a CAC score >100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23-5.54], and 4.6 (95% CI 2.1-9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. CONCLUSIONS: Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Clinical Evaluation of the First Automated Assay for the Detection of Stimulating TSH Receptor Autoantibodies.

Until recently, stimulating TSH receptor autoantibodies (sTRAbs) could only be measured by bioassays. A new assay system, which directly detects sTRAb in sera by applying bridge technology, has been established and is now available as automated chemiluminescence (bridge) immunoassay. We evaluated the automated bridge assay in clinical routine and compared it with a conventional automated TRAb assay (competition assay). Altogether, 226 Graves' disease (GD), 57 autoimmune thyroiditis, 74 non-autoimmune nodular goiter and 49 thyroid cancer patients, as well as 41 healthy controls were retrospectively evaluated. ROC plot analysis based on sera of newly diagnosed GD patients revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (100%) and specificity (99%) were seen at a cut-off level of 0.55 IU/l. The calculated positive predictive value was 94%, whereas the negative was 100%. Applying a ROC plot-derived cut-off of≥0.30 IU/l, derived from sera of GD patients already receiving antithyroid drug therapy for≤6 months, the sensitivity was 99% whereas the specificity was 98%. Detailed comparison of both assay systems used revealed a slightly different distribution of sTRAb and TRAb. Measurement of sTRAb during follow-up revealed a steady decline over one year of follow-up. In summary, our results demonstrate that the new automated bridge assay system for detecting sTRAb has a high sensitivity and specificity for diagnosing GD and to discriminate from other thyroid diseases, respectively. Our study, however, does not provide full evidence that the bridge assay is specific for sTRAb only.

Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia.

Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.

Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.

Diagnostic and prognostic value of absence of coronary artery calcification in patients with stable chest symptoms.

UNLABELLED: The aim of this study was to determine the prognostic value of a coronary artery calcium score (CACS) of 0 in patients with stable chest symptoms and to compare it as a first-line test with bicycle exercise testing (X-ECG). Altogether, 315 consecutive patients over 44 years of age, with stable chest symptoms and no previous diagnosis of coronary artery disease (CAD) visited the outpatient clinic of our community hospital and underwent both CACS and X-ECG. The mean age was 60.54 years (SD 9.7; range 45-88 years). Of these patients, 141 had no detectable coronary calcium (44.8%) We excluded patients who did not sign informed consent (n = 4). Three patients were lost to follow-up. The follow-up group therefore consisted of 134 patients. The mean follow-up period was 44.6 months (25th-75th percentile: 35.5-54.3 months), during which no major adverse cardiac events (MACE) occurred. The negative predictive value (NPV) was 100%. X-ECG was negative in only 89 patients, equivocal in 39 patients and false-positive in 6 patients requiring additional stress myocardial imaging in 45 patients. NPV as a first-line test was therefore 66.4%. IN CONCLUSION: patients over 44 years with stable chest symptoms and no detectable coronary calcium have an excellent prognosis. CACS performs better compared with X-ECG as an initial test in patients with stable chest symptoms.

Reproducibility of Elecsys anti-TSHR test results in a lot-to-lot comparison.

Most recently, a new rapid and fully-automated TSH receptor autoantibody (TRAb) assay has been established. This assay system uses the M22 human monoclonal antibody for competing against the patient's TSH receptor autoantibodies (TRAb) to be detected. The aim of our present study was to compare the reproducibility of TRAb values based on measurements with different TSH receptor preparations in a lot-to-lot comparison. For TRAb values > 2 IU/l the relative differences ranged from -9.0 to +10.0%. The mean difference was 0.28 +/- 8%. For TRAb values around the cutoff for positivity (1.75 IU/l) a higher range of relative differences from -20 up to +15% was obtained. The overall mean of differences was -0.8+/-14%. The data clearly demonstrate that the automated TRAb assay has a high stability in regard to TSH receptor preparations.

Comparison of a solid phase human- versus porcine- thyrotropin receptor-based immunoassay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases.

Thyrotropin receptor (TSHR) antibody (TRAb) assays based on human or porcine TSHR which are coated to a solid phase are the most commonly used detection methods in clinical practice for patients with thyroid diseases. Yet the difference of the diagnostic values of the two TRAb assays is largely unclear. The aim of our present study was to evaluate the clinical perfomance of a solid phase porcine TRAb assay based on an ELISA technique (TRAb-porcine) and a human TRAb assay based on a chemiluminescence signal detection procedure (TRAb-human). Of 158 patients enrolled in the study, 84 suffered from Graves' disease (GD), 34 had Hashimoto's thyroiditis (HT) and 40 had euthyroid nodular thyroid disease (NTD) without signs of autoimmunity. TRAb measurements were performed according to the manufacturer's instructions. The mean values of TRAb titers detected by the TRAb-human and TRAb-porcine assays in patients with GD were 12.14+/-10.80 IU/L and 15.27+/-13.65 IU/L, respectively. TRAb were detected in 80 and 78 out of 84 GD patients by the TRAb-human and TRAb-porcine assay, respectively. The diagnostic sensitivity of the TRAb-human and TRAb-porcine immunoassay was 95.2 and 92.9% respectively, by 100% specificity of both methods. TRAb values in GD patients detected by the TRAb-human and TRAb-porcine assays were significantly correlated (r=0.929, p<0.0001). Our results indicate that the second generation TRAb-porcine assay based on solid phase technology had a slightly lower diagnostic sensitivity compared to the TRAb-human assay.

Validity of S-100 B in patients after brain radiation.

BACKGROUND: S-100B is a calcium binding acute phase protein and a potential biomarker for brain injury. In prior studies elevated plasma S-100B levels were detected in stroke and severe head trauma. The aim of this study was to evaluate whether S-100 B is elevated during cerebral radiotherapy and whether that is associated with adverse outcomes. MATERIAL AND METHODS: In this prospective pilot study, 45 patients (25 males, 20 females, median age 58 (17-81)) underwent cerebral radiation therapy because of a primary or metastaic cerebral malignancy. 39 patients were included in the evaluation. 6 patients died during the study period. S-100 plasma concentrations were measured with an electrochemiluminescence immunoassay on admission and weekly during radiation therapy for the duration of 6 weeks. In 10 healthy young volunteers (5 males, 5 females, median age 32 (28-36)) S-100 B plasma levels were measured weekly for 6 weeks as a negative control. Furthermore, in an active control 10 patients (4 males, 6 females, median age 68 (64-76)) with stroke (7 = major stroke, 3 = lacunar infarct) S- 100 B plasma levels were measured for 7 consecutive days after the event. RESULTS: During radiotherapy S-100 B plasma concentrations increased from median baseline values of 0.030 microg/l to 0.044 microg/l. For the time of radiation therapy most patients showed a mild increase, but absolute plasma values were still within the normal range. In the control group of healthy volunteers S-100 B remained unchanged. In stroke patients S-100 B increased to maximum values of 1.7 microg/l three days after the event. In the 3 patients with lacunar infarcts no increase of S-100 B levels could be detected. CONCLUSION: Brain irradiation leads to a mild increase of S-100 B plasma levels. However, the absolute rise was far weaker compared to that seen in major brain injuries.

Comparison of M22-based ELISA and human-TSH-receptor-based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases.

Previously, a new procedure for measuring serum TSH receptor autoantibodies (TRAb) was reported in which the autoantibodies inhibit binding of a human monoclonal thyroid stimulating antibody M22 to TSHR-coated ELISA plate wells (TRAb ELISA). The aim of the present study was to evaluate the clinical performance of this assay in comparison to the second generation TRAb assay (TRAb LIA) based on the recombinant human TSH-receptor and chemiluminescence technology (TRAb LIA). Among the 158 patients, 84 patients suffered from Graves' disease (GD), 34 patients had Hashimoto's thyroiditis (HT), and 40 patients had euthyroid nodular thyroid disease (NTD) without signs of autoimmunity. TRAb measurements were performed according to the manufacturer's instructions. Out of 84 GD patients, 80 (95.2%) were TRAb positive as detected by the TRAb LIA. One GD patient had TRAb values within the grey zone (1.0-1.5 IU/l). All patients with HT and NTD were negative except in 6 (8.1%) cases whose TRAb values were within the grey zone. On the basis of the recommended cutoff value (TRAb 1.0 IU/l), the TRAb ELISA found 78 of 84 (92.9%) GD patients to be TRAb positive. None of the patients with HT, but two cases (5.0%) with NTD were TRAb positive. The diagnostic sensitivity of the TRAb LIA and TRAb ELISA assays was 95.2 and 92.9%, while the specificity was 100% and 97.3%, respectively. There was a close correlation (r=0.968, p<0.0001) between both assays in 84 patients with GD. Additionally, the between-run imprecision close to the cutoff limit was assessed. The calculated between-run coefficient of variation (CV) of the TRAb ELISA was 28.2% at the recommended cutoff value of 1.0 IU/l. Due to the evaluated imprecision data we propose a higher cutoff value correlating with a between-run CV of 20% (functional assay sensitivity). Our results indicate that due to a worse imprecision the TRAb ELISA has a slightly lower sensitivity and specificity compared to the TRAb LIA assay. These findings suggest that the M22 monoclonal antibody-based TRAb ELISA is not as reliable as other second generation TRAb assays in the diagnosis of Graves' diseases.

Circulating chemokines in patients with autoimmune thyroid diseases.

Chemokines are a group of small proteins that recruit different leukocyte subtypes to sites of inflammation and play important roles in initiating and maintaining immunological responses in autoimmune endocrine diseases including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Previous studies have found increased gene and protein expression of different kinds of chemokines not only within the thyroid gland but also within thyroid cells in GD or HT patients. A few studies have determined serum levels of chemokines, with conflicting results. We measured circulating concentrations of CCL2, CCL5, CXCL9, and CXCL10 in patients with GD, HT, and nontoxic nodular thyroid disease (NNT). While CCL2 and CXCL9 concentrations were comparable in patients with either AITD or NNT, CCL5 was significantly increased in GD patients compared with HT or NNT subjects. In contrast, CXCL10 levels were lower in patients with GD, but the difference was statistically significant only when compared with patients with HT (p=0.0018). Importantly, GD patients who relapsed or went into remission had significantly different levels of CXCL9 (p=0.0252). Serum levels of CCL2, CCL5, CXCL9, and CXCL10 did not reveal any correlation with thyroid volume; with the levels of thyrotropin (TSH), FT3, or FT4; or with the titers of TSH receptor antibody and thyroperoxidase antibody. These data suggest that the expression patterns of chemokines in various thyroid diseases differ from each other, which may reflect the distinct immune responses in HT and GD.

[Coronary calcium score using CT in the diagnosis of 2 patients with acute chest pain]. / Coronaire calciumscore met behulp van CT bij de diagnostiek van 2 patiënten met acute thoracale pijn.

A 38-year-old man presented with severe retrosternal pain that had persisted for several days. Physical examination, resting ECG and circulating levels of cardiac markers were normal. The patient had continuous pain during a bicycle test, but no signs of myocardial ischaemia were found. A CT scan was performed, and the resulting CT calcium score was 40 Agatston units (AU; > 90th percentile). Coronary angiography showed severe coronary artery disease. An arterial bypass operation took place. Recovery was uncomplicated and the patient remained free of symptoms. A 55-year-old man experienced midsternal pain that lasted 20 minutes before spontaneously subsiding. The ECG and troponine levels were normal. One week later, there were no abnormalities during a bicycle test and the CT calcium score was 0 AU. Therefore, there was no indication of coronary artery disease and a watchful waiting approach was taken. After 1 year of follow-up, the patient remained free of symptoms. For patients aged 45 years or more with acute chest pain and a CT calcium score of 0 AU, further cardiac evaluation is unnecessary. For patients aged less than 45 years, a CT calcium score greater than o is abnormal and requires additional cardiac evaluation.

Results from a multicenter evaluation of the 4th generation Elecsys Troponin T assay.

BACKGROUND AND OBJECTIVE: Discrepancies between serum and heparin plasma samples have been described for many commercial troponin assays including the cardiac troponin T (cTnT) assay. Using the current 3rd generation Elecsys Troponin T immunoassay, heparin plasma cannot be recommended for the determination of cTnT due to systematic lower test results caused by a direct interference of the immunoassay by heparin. The purpose of the multicenter study was to evaluate the analytical performance of an improved 4th generation Elecsys Troponin T immunoassay with a special focus on the comparability of cTnT results determined in heparin plasma and serum. METHODS AND RESULTS: The multicenter evaluation was performed in 10 clinical laboratories according to a standardized protocol (Roche Diagnostics, Penzberg, Germany, Study No. B05P008). The Elecsys Troponin T immunoassay was performed on the Modular Analytics E170 and Elecsys 2010 systems. Intraassay imprecision (n = 21) and total imprecision (2 runs/d, 10 days, triplicate measurements) were evaluated using 2 commercial controls (Roche Diagnostics) and 6 different serum pools (cTnT: 0.0140 - 4.102 microg/L). Intraassay CVs ranged from 0.73 to 3.22%. Total imprecision CVs ranged from 3.61 to 35.45% (cTnT < 0.1 microg/L) and 1.82 to 9.09% (cTnT > 0.1 microg/L), respectively. The cut-off for myocardial necrosis was determined to be 0.03 microg/L using the 10% total imprecision CV criteria. Linearity was assessed by serial dilutions of 6 different serum samples using cTnT negative serum pools. Linearity was proven up to 21.3 microg/L (recoveries: 90% - 110%). Regression data of all comparison studies were calculated according to the method of Passing and Bablok. The method comparison between the 4th generation and the commercially available cTnT immunoassay showed highly similar results across the whole measuring range (0.01 - 25.0 microg/L): y = 1.024x -0.001, r = 0.998; n = 988. Using the commercially available cTnT reagent, the serum to heparin plasma comparison yielded a systematic bias to approximately 8% lower cTnT results in heparin plasma. However, suitable comparability was obtained using the 4th generation Elecsys cTnT assay. The regression analysis (serum vs. heparin plasma) across the studied measuring range (cTnT: 0.01 - 14 microg/L) yielded the following equation: y = 0.975x + 0.001; r = 0.986; n = 403. However, rare individual serum to matched heparin plasma samples still yielded poor comparability (deviation > 20%) using the 4th generation Elecsys Troponin T immunoassay. CONCLUSION: Our data confirm an excellent analytical performance of the improved troponin T immunoassay. Most importantly, no systematic bias between cTnT results determined in serum and heparin plasma was observed from data obtained in 7 evaluation sites. The performance of the 4th generation Elecsys Troponin T assay is therefore comparable to other commercially available troponin immunoassays. Further studies are necessary to investigate the cause of poor comparability of cTnT results in rare individual serum to matched heparin plasma samples.

Urinary excretion of deoxypyridinoline in Perthes' disease: a prospective, controlled comparative study in 83 children.

Our aim was to investigate the relationship between urinary excretion of deoxypyridinoline (DPD) as a marker of bone resorption, and Perthes' disease. There were 39 children with Perthes' disease in the florid stage who collected first-morning urine samples at regular intervals of at least three months. The level of urinary DPD was analysed by chemiluminescence immunoassay and was correlated with the radiological stage of the disease as classified by Waldenström, and the severity of epiphyseal involvement according to the classification systems of Catterall and Herring. The urinary DPD levels of a group of 44 healthy children were used as a control. The median urinary DPD/creatinine (CREA) ratio was significantly reduced (p < 0.0001) in the condensation stage and increased to slightly elevated values at the final stage (p = 0.05) when compared with that of the control group. Herring-C patients showed significantly lower median DPD/CREA ratios than Herring-B patients (p = 0.03). The significantly decreased median DPD/CREA ratio in early Perthes' disease indicated a reduced bone turnover and supports the theory of a systemic aetiology. Urinary levels of DPD may therefore be used to monitor the course of Perthes' disease.

Serum cystatin C is a suitable marker for routine monitoring of renal function in pediatric cancer patients, especially of very young age.

BACKGROUND: Monitoring renal function is crucial in children undergoing chemotherapy. To date, a combination of routine serum creatinine (SCR) monitoring with occasional determination of creatinine clearance ratio (CCR) is widely used as clinical standard for this purpose. Both methods have their limitations regarding diagnostic value (SCR) or practicability (CCR), especially in young children. Diagnostic alternatives, such as glomerular filtration rate (GFR) estimation formulas have not been proved to be superior. The aim of the study was to evaluate whether serum cystatin C (CysC) may have a diagnostic impact on pediatric patients. PROCEDURE: CysC, SCR, several GFR estimation formulas (Counahan-Barratt, Ghazali-Barratt, Schwartz, Shull, Traub), and CCR were studied in 80 pediatric cancer patients (age range: 0.17-17.9 years) during their chemotherapy. Special attention was given to children under the age of 3 in whom accurate urine collection for CCR is difficult. RESULTS: All parameters correlated similarly well with CCR. Total accuracy was 66% and 67% for CysC and SCR, respectively. In very young children (<3 years), correlation with CCR was for CysC r = -0.74 with an area under the curve (AUC) of 0.646, and for SCR r = -0.27 with AUC = 0.594. Total accuracy was 60% for CysC, 50% for SCR. CONCLUSIONS: CysC represents a suitable marker for monitoring renal function in pediatric cancer patients. In young children (<3 years), CysC may have a better diagnostic value than SCR. Future studies should show if CysC can improve renal monitoring by replacing SCR, especially in very young children.

Effects of candesartan and perindopril on renal function, TGF-beta1 plasma levels and excretion of prostaglandins in stable renal allograft recipients.

AIMS: Although on account of their nephroprotective effects, ACE inhibitors and angiotensin receptor antagonists appear to be advantageous for patients after renal transplantation, their use in these patients has been limited up to now. This is in part due to the risk of inducing a decrease in the glomerular filtration pressure gradient with subsequent impairment of allograft function. The aim of the present study was to investigate the effects of ACE inhibitors and angiotensin receptor antagonists on renal function, excretion of prostaglandins as a parameter of glomerular hemodynamics and TGF-beta1 plasma levels during an 8-week withdrawal phase in pretreated patients. PATIENTS AND METHODS: Sixteen patients with stable long-term allograft function undergoing therapy with candesartan (group 1) and 16 patients with stable long-term allograft function undergoing therapy with perindopril (group 2) were included in the study. Any signs of chronic allograft dysfunction were defined as exclusion criteria. Renal function, albuminuria, TGF-beta1 plasma levels as well as the excretion of thromboxane B2 and 6-keto-prostaglandin-F-1alpha were monitored during an 8-week withdrawal phase of the angiotensin receptor antagonist or ACE inhibitor, respectively. Normotension was maintained throughout the study period through adjustment of other anti-hypertensive drugs. RESULTS: Creatinine clearance as well as TGF-beta1 plasma levels and the excretion of prostaglandins remained unchanged after discontinuation of candesartan or perindopril. However, after withdrawal of the substances a significant increase in albuminuria was noted in both patient groups throughout the observation period. After 8 weeks, median albuminuria had increased by 63% in group 1 and by 163% in group 2. CONCLUSIONS: We were able to demonstrate that the use of ACE inhibitors and angiotensin receptor antagonists in patients after renal transplantation is safe. Favorable effects of both substances on albuminuria were detectable in patients who showed no signs of chronic allograft dysfunction according to the usual criteria. Therefore, a nephroprotective effect of candesartan as well as of perindopril, is highly probable in patients after renal transplantation. Further investigations regarding routine use in these patients are therefore mandatory.

[Electrophysiologic effects of K+ and Mg2+ in the hypoxia model]. / Elektrophysiologische Wirkungen von K+ und Mg2+ im Hypoxiemodell.

The influence of Mg2+ and K+ on reoxygenation arrhythmias following 18 min of hypoxia (pO2 about 1 mm Hg, no glucose, 10 mmol/l2-desoxyglucose) has been investigated in isolated guinea-pig left atria (stimulation rate 1 Hz). Duration of reoxygenation arrhythmias was slightly reduced by increase in Mg2+ (0.6 to 4.8 mmol/l) and enhanced by decrease in Mg2+ (0.1 mmol/l), however, this effect was not significantly different from control (0.6 mmol/l). In contrast, low K+ (< 4 mmol/l) led to a significant (p < or = 0.05) prolongation and high K+ (> 5 mmol/l) to a significant abbreviation of reoxygenation arrhythmias. Increase in Mg2+ significantly attenuated the proarrhythmic effects of low K+ and enhanced the antiarrhythmic effects of high K+. Furthermore, the influence of Mg2+ and K+ on action potential parameters has been investigated in hypoxic guinea-pig papillary muscles (pO2 65 to 75 mm Hg). Action potential duration at 30% (APD30) and 90% repolarization (APD90) were increased by both electrolytes whereas resting potential, amplitude of the action potential and maximum upstroke velocity were not changed with the exception of a depolarization induced by elevated K+. 1 mmol/l Mg2+ increased APD30 to 145 +/- 16% (n = 6, p < 0.05) and APD90 to 117 +/- 9% (n = 6, p > 0.05) of control (0.6 mmol/l Mg2+). Increase of K+ from 2 mmol/l (control) to 4.7 mmol/l increased APD30 to 188 +/- 13% (n = 6, p < 0.05) and APD90 to 136 +/- 13% (n = 6, p < 0.05). The delay in repolarization observed already in therapeutic concentrations showed no inverse use dependence as it was not attenuated if stimulation rate was increased from 0.17 to 1 Hz which is in contrast to the effects of class 3 antiarrhythmic drugs (for example sotalol). Increase in concentration of both electrolytes led to an additive increase in action potential duration. Mg2+ (0.6 to 4.8 mmol/l) suppressed late afterdepolarizations and -contractions in K(+)-depolarized guinea-pig papillary muscles (27 mmol/l K+, 0.5 mmol/l Ba2+) induced by 2 x 10(-8) mol/l isoprenaline. The change in the triphasic contraction cycle by elevation of Mg2+ indicates that Mg2+ additionally increases stimulus-induced release of Ca2+ from the sarcoplasmic reticulum and reduces slow Ca2+ inward current. The described electrophysiological actions of the electrolytes represent mechanisms, which may explain their antiarrhythmic actions observed in clinical studies.