Lorenz Risch

Effect of volume loading with 1 liter intravenous infusions of 0.9% saline, 4% succinylated gelatine (Gelofusine) and 6% hydroxyethyl starch (Voluven) on blood volume and endocrine responses: A randomized, three-way crossover study in healthy volunteers

Objective: To study the changes in blood volume and hormones controlling sodium and water homeostasis after infusions of 0.9% saline, Gelofusine (4% succinylated gelatin in 0.7% saline, weight-average molecular weight 30 kD), and Voluven (6% hydroxyethyl starch in 0.9% saline, weight-average molecular weight 130 kD) in healthy volunteers. Design: Randomized, three-way crossover study. Setting: University teaching hospital. Subjects: Ten healthy adult male volunteers. Interventions: Volunteers received 1-L infusions of 0.9% saline, Gelofusine, and Voluven over 1 hr on three occasions. Body weight, hematocrit, serum biochemistry, and plasma concentrations of vasopressin, aldosterone, brain natriuretic peptide, and total renin were measured before infusion and hourly thereafter for 6 hrs. Changes in body water, blood volume, and extravascular fluid volume were calculated. Measurements and Main Results: Although changes in body weight (total body water) after the infusions were similar, blood volume expansion by the two colloids was significantly greater than that produced by 0.9% saline (p < .01). At the end of infusions, 68%, 21%, and 16% of the infused volumes of 0.9% saline, Gelofusine, and Voluven, respectively, had escaped from the intravascular space to the extravascular space. Over the 6 hrs, the magnitude and duration of blood volume expansion by the two colloids were similar (p = .70). There were no significant differences in urinary volume, osmolality, and sodium content after the three infusions. Hormonal changes were similar after the three infusions, with the increase in natriuretic peptide being transient. The reduction in aldosterone and total renin concentrations was more sustained. Conclusions: The effects of Gelofusine and Voluven were similar despite the 100 kD difference in weight-average molecular weight. Excretion of an acute fluid load containing sodium and chloride may be dependent on a sustained suppression of the renin-angiotensin-aldosterone system rather than on natriuretic peptides.

Stability of hematological analytes depends on the hematology analyser used : A stability study with Bayer Advia 120, Beckman Coulter LH 750 and Sysmex XE 2100

AIM With the availability of newer hematology analysers, novel measurement techniques are being introduced into daily routine. As analyte stability may differ according to the employed measurement technique, the aim of this study was to assess the stability of hematologic analytes on different hematology analysers. METHODS We investigated the effect of storage time and storage temperature on sample stability on three newer analytical systems (Advia 120, Bayer Diagnostics; XE 2100, Sysmex and LH 750, Beckman Coulter). Samples were obtained from 64 healthy volunteers and stored at room temperature as well at 4-8 degrees C in order to conduct analysis at different timepoints up to 72 h after blood was drawn. Sample stability was assessed by the graphical truncated normal sequential test. A parameter was considered stable, when its average change was smaller than one coefficient of variation CV (%) of the assessed method, allowing a 5% risk of error. RESULTS Red blood cell counts, mean corpuscular hemoglobin (MCH) and hemoglobin are least affected by storage temperature and showed stability for at least 48 h, depending on analyser utilized. While reticulocytes, mean corpuscular volume (MCV), hematocrit and leukocyte counts were more stable at 4-8 degrees C, thrombocytes exhibited a better stability at RT. The white blood cell (WBC) subpopulations changed over time with a decrease in eosinophils and lymphocytes and an increase in neutrophils at 4-8 degrees C. Further, the stability pattern of WBC subpopulations was significantly different among the 3 investigated analysers with some analytes only displaying a stability of 4 h. CONCLUSIONS Analyte stability of hematological parameters varies not only according to the investigated parameter but also according to storage temperature and the employed measurement system. Depending on the analyte sample stability differences among the different analytical systems are considerable.

Heparin-induced thrombocytopenia in paediatrics: clinical characteristics, therapy and outcomes

Objective: Reports on heparin-induced thrombocytopenia (HIT) in paediatrics are confined to isolated case reports. The objective was to systematically combine the published data. Design and setting: Cases were identified by MEDLINE search and review of bibliographies. Patients: We included subjects reported with HIT, collecting patient demographics, clinical and laboratory characteristics, therapeutic regimens and outcomes. Measurements and results: Reports on 70 patients were retrieved. In a majority of children, HIT occurred during hospitalisation in a paediatric ICU. In most patients, the typical onset pattern was reported, although rapid-onset-pattern HIT occurred in some. The median platelet-count nadir was 54×109/l; 11% of reported patients had nadirs in the normal range. Clinical symptoms included isolated thrombocytopenia and solitary or combined venous, arterial and intracardiac thromboembolism, sometimes catheter-related. Pulmonary embolism and major bleeding were rarely described. Confirmatory functional or antigenic testing of HIT antibodies showed a similar cumulative sensitivity of about 88%. An unfavourable outcome (death/limb amputation) was reported in 42.1% of patients without therapy and in 18% of patients treated with danaparoid, lepirudin, or argatroban. Conclusions: HIT in children mainly occurs in paediatric intensive care with diagnostic features and outcomes similar to those seen in adults. HIT cannot be ruled out based on normal platelet counts or occurrence after fewer than 5 days of heparin exposure. Children should be presumed to suffer from HIT based on clinical grounds and treated accordingly (immediate heparin withdrawal and alternative anticoagulation). Alternative anticoagulation with danaparoid, lepirudin and argatroban appears to improve outcomes.

Comparison of MALDI TOF with conventional identification of clinically relevant bacteria.

BACKGROUND A completely new approach to diagnose microbial agents at least one day earlier based on mass spectrometric analysis becomes possible in the microbiology laboratory: MALDI TOF: matrix-assisted laser desorption/ionisation time-of-flight. Comparison between results of the new procedure with those obtained by conventional testing is mandatory. METHODS 204 clinical isolates grown on agar plates were analysed both, by the MALDI TOF Bruker microflex apparatus and by conventional identification using the VITEK II and API systems, both from bioMérieux. RESULTS Of the identified isolates, 72 were gram-positive and 130 gram-negative; 2 were yeasts (candida). Concordance was seen with 61/72 (85%) of the Gram-positive bacteria and with 115/130 (88%) of the Gram-negative bacteria. In 27 samples (13.2%), a discrepancy of the species and/or genus was obvious. The discrepancy appeared with 16 gram-negative (12.2%) and with 11 gram-positive germs (15.3%, n.s.). In the latter group, 6 samples showed discordance with Streptococcus pneumoniae (MALDI) and Streptococcus mitis/oralis (conventional identification) constellation. Among gram-negative samples, most differences occurred on the species level only, e.g. Enterobacter cloacae versus Enterobacter kobei. In 5 cases, discordance was major and appeared on the genus level: Enterobacter/Raoultella, Streptococcus/Gemella, Pseumdomonas/Burkholderia, Microbacter/Sphingomonas and Candida/Cryptococcus. The most outstanding difference was Microbacterium arborescens (MALDI TOF) and Sphingomonas paucimobilis (conventional). Molecular biological identification of two Streptococcus mitis group bacteria confirmed the erroneous diagnosis by MALDI TOF of Streptococcus pneumoniae. CONCLUSION Good comparability between MALDI TOF analysis and conventional identification procedures (86.8%) but special caution is needed when identifying streptococcal species.

Age-specific differences between conventional and ambulatory daytime blood pressure values.

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.

The -11377 C>G promoter variant of the adiponectin gene, prevalence of coronary atherosclerosis, and incidence of vascular events in men.

No prospective data demonstrating an association between the –11377 C>G adiponectin gene promoter variant and cardiovascular risk are available.We therefore prospectively evaluated the cardiovascular risk associated with adiponectin gene single nucleotide polmorphisms (SNPs) including SNP –11377 in a consecutive series of men undergoing coronary angiography. We recorded vascular events over four years in 402 men undergoing coronary angiography for the evaluation of coronary artery disease. No significant associations of SNPs +276 G>T and +45 T>G with serum adiponectin,with significant coronary stenoses >50%, or with vascular events were observed. However, for SNP –11377 C>G, serum adiponectin levels significantly decreased (ptrend = 0.003), and the prevalence of significant coronary stenoses significantly increased from the CC over the GC to the GG genotype (ptrend = 0.004). Prospectively, the risk of vascular events significantly increased from the CC over the CG to the GG genotype of this SNP (adjusted hazard ratios 1.555 [0.957 – 2.525] and 2.309 [1.067 – 4.998],respectively;ptrend = 0.014).The –11377 C>G adiponectin gene promoter variant is i) associated with decreased serum adiponectin levels, ii) correlated with the presence of coronary atherosclerosis and iii) significantly predictive of vascular events among men undergoing coronary angiography.

Metabolic and anti-inflammatory benefits of eccentric endurance exercise – a pilot study

Background  Eccentric endurance exercise (e.g. hiking downwards) is less strenuous than concentric exercise (e.g. hiking upwards) but its potential to reduce cardiovascular risk is unknown.

Alanine aminotransferase and gamma-glutamyl transferase are associated with the metabolic syndrome but not with angiographically determined coronary atherosclerosis.

BACKGROUND Recently, elevated liver enzymes have attracted great interest as potential novel markers of cardiovascular risk. Their association with angiographically determined coronary artery disease (CAD) is unknown. METHODS We enrolled 1000 consecutive patients undergoing coronary angiography for the evaluation of suspected or established stable CAD. The metabolic syndrome (MetS) was defined according to ATP-III criteria; significant CAD was diagnosed in the presence of coronary stenoses with lumen narrowing >or=50%. RESULTS Serum alanine aminotransferase (ALT), the ALT/aspartate aminotransferase (AST) ratio, and serum gamma-glutamyl transferase (GGT) were significantly higher in patients with the MetS than in subjects without the MetS (34+/-21 vs. 29+/-20 U/l; p<0.001, 1.16+/-0.39 vs. 1.00+/-0.36 U/l, p<0.001; and 53+/-88 vs. 43+/-57 U/l, p=0.001, respectively) but were similar in patients with significant CAD as in those who did not have significant CAD at angiography (p=0.592; p=0.731, and p=0.716, respectively). Analysis of covariance after multivariate adjustment including alcohol consumption confirmed that ALT, ALT/AST ratio, and GGT were significantly and independently associated with the MetS but not with significant CAD. CONCLUSIONS ALT, the ALT/AST ratio, and GGT are associated with the MetS but not with angiographically determined coronary atherosclerosis.

Relation of Albuminuria to Angiographically Determined Coronary Arterial Narrowing in Patients With and Without Type 2 Diabetes Mellitus and Stable or Suspected Coronary Artery Disease

Albuminuria is associated with atherothrombotic events and all-cause mortality in patients with and without diabetes. However, it is not known whether albuminuria is associated with atherosclerosis per se in the same manner. The present study included 914 consecutive white patients who had been referred for coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Albuminuria was defined as a urinary albumin/creatinine ratio ≥ 30 μg/mg. Microalbuminuria was defined as 30 to 300 μg albumin/mg creatinine, and macroalbuminuria as a urinary albumin/creatinine ratio of ≥ 300 μg/mg. The prevalence of stenoses of ≥ 50% was significantly greater in patients with albuminuria than in those with normoalbuminuria (66% vs 51%; p <0.001). Logistic regression analysis, adjusted for age, gender, diabetes, smoking, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, body mass index, estimated glomerular filtration rate, and the use of angiotensin-converting enzyme inhibitors/angiotensin II antagonists, aspirin, and statins, confirmed that albuminuria was significantly associated with stenoses ≥ 50% (standardized adjusted odds ratio [OR] 1.68, 95% confidence interval [CI] 1.15 to 2.44; p = 0.007). The adjusted OR was 1.54 (95% CI 1.03 to 2.30; p = 0.034) for microalbuminuria and 2.55 (95% CI 1.14 to 5.72; p = 0.023) for macroalbuminuria. This association was significant in the subgroup of patients with type 2 diabetes (OR 1.66, 95% CI 1.01 to 2.74; p = 0.045) and in those without diabetes (OR 1.42, 95% CI 1.05 to 1.92; p = 0.023). An interaction term urinary albumin/creatinine ratio*diabetes was not significant (p = 0.579). In conclusion, micro- and macroalbuminuria were strongly associated with angiographically determined coronary atherosclerosis in both patients with and those without type 2 diabetes mellitus, independent of conventional cardiovascular risk factors and the estimated glomerular filtration rate.

The serum uromodulin level is associated with kidney function

Abstract Background: In chronic kidney diseases of various etiologies, the urinary excretion of uromodulin is usually decreased in parallel with the glomerular filtration rate. This study aimed to investigate whether serum uromodulin is associated with kidney function. Methods: Within the framework of the Seniorlabor study, a subset of subjectively healthy individuals 60 years of age and older were included in the study. Serum uromodulin was measured with ELISA. The relationship between serum uromodulin and different stages of kidney function (i.e., cystatin C-based 2012-CKD-EPI eGFRCysC>90 mL/min/1.73 m2, 60–89 mL/min/1.73 m2, 45–59 mL/min/1.73 m2, and <45 mL/min/1.73 m2) was investigated. Furthermore, the relationship between serum uromodulin and other markers of kidney function (i.e., creatinine, cystatin C, and urea) was assessed. Results: In total, 289 participants (140 males/149 females; mean age 71±7 years) were included in the study. There were significant differences in serum uromodulin among the four groups according to different kidney function stages (p<0.001). Serum uromodulin displayed inverse relationships with creatinine (r=–0.39), cystatin C (r=–0.42), and urea (r=–0.30) and, correspondingly, a positive relationship with eGFRCysC (r=0.38, p<0.001 for all). These associations remained intact when fitting a regression model that incorporated age, gender, body mass index, and current smoking status as covariates. Conclusions: Serum uromodulin behaves in a manner opposite that of the different conventional renal retention markers by displaying lower concentrations with decreasing kidney function. As uromodulin is produced by the cells of the thick ascending limb of the loop of Henle, lower uromodulin serum levels may reflect a reduction in number or function of these cells in chronic kidney disease.