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Biomedical subjects

Andreas R Huber

Publications and source records attributed to Andreas R Huber.

At least 19 recordsLinked to original sources

Time-course of quantitative urinary leukocytes and bacteria counts during antibiotic therapy in women with symptoms of urinary tract infection.

BACKGROUND: Urinary tract infections are generally diagnosed by test strips and microscopic semi-quantitative sediment analyses. However, results are uncertain because of lacking standardisation and limited sensitivity in low-count-bacteriuria. Flow cytometry UF-100 was used to analyse particles quantitatively in urine in women with urinary tract infections during the period of antibiotic therapy. The aim was to follow the courses of leukocytes and bacteria during infections and to gain information about the reasons for successful or unsuccessful outcomes. METHOD: Quantitative leukocytes and bacterial counts in urine of 16 symptomatic women were performed at presentation and each day during the antibiotic treatment by flow cytometry UF-100. RESULTS: Leukocytes in urine were between 30 and 15,000 (x10(6)/L) at presentation (cut-off 20x10(6)/L). Bacteria counts from flow cytometry were mainly 5x10(9)/L-100x10(9)/L (cut-off of 3x10(9)/L). The deepest decreases in cell counts were noted during the first 24 h after initiation of therapy and gained normal values at the end of treatment in successful outcomes. A slower or no decrease was noted in unsuccessful treatments. CONCLUSION: The precise leukocyte and bacteria counting by flow cytometry and their follow-up during urinary tract infections gave early information about outcomes of therapy.

Adolescent↗

Effective control of persistent hyperparathyroidism with cinacalcet in renal allograft recipients.

BACKGROUND: Cinacalcet rapidly normalizes serum calcium and reduces intact parathyroid hormone (PTH) levels in renal transplant patients with hypercalcaemia and persistent hyperparathyroidism. The aim of this study is to evaluate the 6 months efficacy of cinacalcet and the effect of cinacalcet withdrawal on serum calcium and PTH in such patients. Furthermore, the impact of cinacalcet on bone turnover and quality of life was assessed. METHODS: Twelve renal allograft recipients with hypercalcaemia due to persistent hyperparathyroidism were treated with cinacalcet for 26 weeks. Cinacalcet was then withdrawn to check for recurrence of hypercalcaemia. RESULTS: Cinacalcet maintained normocalcaemia in all patients from week 4 to 26, and PTH significantly decreased and remained suppressed. Serum phosphate increased, whereas the serum calcium-phosphate product remained unchanged. The excretion of calcium and phosphate in the 24 h urine had tendency to decrease. After cinacalcet was withdrawn, hypercalcaemia recurred rapidly and PTH increased to baseline values. Renal function remained stable, proteinuria was unchanged and no allograft rejection was observed. During treatment with cinacalcet, total and bone-specific alkaline phosphatase increased, whereas the urinary deoxypyridinoline-creatinine ratio did not change significantly, suggesting enhanced bone formation. Quality of life assessed at weeks 10 and 26 remained unchanged compared with baseline. CONCLUSIONS: In conclusion, continued treatment with cinacalcet is required to maintain long-term normocalcaemia and to suppress the enhanced PTH production in renal transplant recipients with persistent hyperparathyroidism.

Aged↗

New "plasma referenced" POCT glucose monitoring systems--are they suitable for glucose monitoring and diagnosis of diabetes?

BACKGROUND: Results from portable glucose meters should be reported as plasma values as recommended by IFCC. Three new "plasma calibrated" blood glucose meters (Abbott Precision Xcceed, Bayer Ascensia Contour and Roche Accu-Chek Aviva) were compared against laboratory venous plasma glucose measurements to determine their suitability for patient monitoring and diabetes diagnosis. METHODS: 115 capillary blood samples were analyzed on each of the three meters and compared to venous plasma measurements on the Dade Behring RXL analyzer (Hexokinase method). RESULTS: We found a significant positive bias of all meters compared to the laboratory reference method. Deviations of more than 10% were seen in more than a third of all glucose values in all three devices. 13%, 8.7% and 10.4%, respectively, of the values from the Abbott, Bayer and Roche devices fell in zone B or C of the Parkes' error grid. CONCLUSIONS: Neither glucose meter met the ADA or the NACB goals and should therefore not be used as screening tests to diagnose diabetes but are well suitable for patient monitoring.

Adult↗

[Abdominal pain, indigestion and eosinophilia].

A 56 years old swiss man suffers of recurrent abdominal cramps with episodes of diarrhea and profuse expectorations. The routine laboratory shows principally a massive eosinophilia and elevated IgE in peripheral blood. After excluding the most frequent causes of eosinophilia, further laboratory investigations shows increased levels antinuclear and anti-SSA antibodies, elevated IgG4, increased pancreatic amylase and intestinal eosinophilia. We consider two etiologies: the hypereosinophilic syndrome, diagnostic of exclusion, and the autoimmune pancreatitis. Although we have not sufficient arguments in favour of an autoimmune pancreatitis, these two entities present some similar points.

Abdominal Pain↗

Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans.

UNLABELLED: In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that this peptide modulates fluid intake and increases renal sodium excretion in healthy volunteers and in patients with diabetes mellitus type 2. The effect of GLP-1 on thirst, water intake and on osmoregulation has, however, not been examined in detail in humans. METHODS: Seventeen healthy male subjects were enrolled in two double-blind, placebo-controlled studies. In study part A, 8 volunteers participated in a protocol with an intravenous salt load of 26.7 +/- 0.9 g comparing the effect of an infusion of GLP-1 (1.5 pmol/kg x min) to isotonic saline (placebo). Sodium excretion and water intake were measured. In part B, 9 volunteers were challenged with an oral salt load of 27.7 +/- 0.5 g; sodium excretion and water intake were determined comparing an infusion of GLP-1 (1.5 pmol/kg x min) to isotonic saline (placebo). In part C, intestinal biopsies along the gastrointestinal tract were obtained from 14 healthy subjects. Expression of human GLP-1 receptor mRNA was measured by real-time polymerase chain reaction. RESULTS: In study part A, an increase in renal sodium excretion was demonstrated: FeNa rose from 1.6 +/- 0.3 (placebo) to 2.7 +/- 0.2% (GLP-1; p = 0.0005). There was no difference in water consumption between the two treatments: 1,291 +/- 69 (saline) vs. 1,228 +/- 74 ml (GLP-1; p = 0.49). In part B, an oral salt challenge of 27.7 +/- 0.5 g led to an increased renal excretion of sodium during GLP-1: FeNa increased from 1.6 +/- 0.2% (placebo) to 2.0 +/- 0.2% (GLP-1; p = 0.012). In contrast to part A, oral water intake was reduced by 36% under GLP-1 treatment: 1,848 +/- 331 ml (placebo) vs. 1,181 +/- 177 ml (GLP-1; p = 0.0414). Three subjects in part B did not finish treatment with GLP-1 because of diarrhea. Human GLP-1 receptor mRNA expression was highest in the proximal human small intestine compared to terminal ileum and colon (p < 0.02). CONCLUSIONS: GLP-1 acts on renal tissue reducing sodium absorption, probably via similar sodium transporters, which also may be localized in the gastrointestinal tract. This hypothesis needs to be confirmed by further studies.

Adult↗

Increased sensitivity in detecting renal impairments by quantitative measurement of marker protein excretion compared to detection of pathological particles in urine sediment analysis.

BACKGROUND: Positive test strip results, pathological particles in urine and the presence of proteinuria are common findings in nephropathies. A comparison between these methods and renal biopsies became available with the introduction of quantitative measurement of marker proteins (albumin, transferrin, IgG, alpha(1)-microglobulin, retinol binding protein, alpha(2)-macroglobulin, Bence Jones proteins) and standardised urine sediment analysis by flow cytometry or microscopy. METHODS: A total of 400 urine samples were examined using marker protein patterns, test strips and quantitative sediment analyses. RESULTS: Results from standardised urine sediment analyses were compared with the excretion of renal marker proteins. Increased erythrocyte and leukocyte counts in urine were observed in only 29% and 39% of the samples for which pathological protein excretion was found. The sensitivity in detecting pathological particles in urine sediment, such as casts and/or dysmorphic erythrocytes, was only 19%. Renal biopsies from 65 patients who were classified as pathological were compared with proteinuria and sediment analyses. Increased excretion of marker proteins was found in all cases, whereas only 41% of the cellular urine sediments showed pathological results. CONCLUSIONS: Quantitative measurement of marker proteins from both the glomerular and tubular sides should be used upfront as screening parameters for the early detection of renal disorders.

Alpha-Globulins↗

Renal function--estimation of glomerular filtration rate.

Assessment and follow-up of renal dysfunction is important in the early detection and management of chronic kidney disease. The glomerular filtration rate (GFR) is the most accurate measurement of kidney disease and is reduced before the onset of clinical symptoms. Drawbacks to the measurement of GFR include the high cost and incompatibility with routine laboratory monitoring. Serum creatinine determination is a mainstay in the routine laboratory profile of renal function. The measurement of serum cystatin C has been proposed as a more sensitive marker for GFR. According to National Kidney Foundation-K/DOQ1 clinical guidelines for chronic kidney disease, serum markers should not be used alone to assess GFR. Based on prediction equations, clinical laboratories should report an estimate of GFR, in addition to reporting the serum value. In this article, information is presented on how best to estimate GFR using prediction equations for adults and for children. Using serum creatinine concentration with the Modification of Diet in Renal Disease (MDRD) study equation offers a suitable estimation of GFR in adults. The cystatin C prediction equation with the use of a prepubertal factor seems superior to creatinine-based prediction equations in children of <14 years.

Algorithms↗

Assessing glomerular filtration rate in renal transplant recipients by estimates derived from serum measurements of creatinine and cystatin C.

BACKGROUND: Assessing glomerular filtration rate (GFR) is of importance in the surveillance of renal transplant recipients. As serum markers alone are inaccurate for estimating GFR, several equations have been developed with the aim of translating a serum value into a corresponding and more accurate GFR. The present study investigated the diagnostic characteristics of GFR estimates obtained by the simplified MDRD formula and the cystatin C based estimate described by Larsson et al. METHODS: Prospective study in 29 stable renal transplant recipients. GFR was assessed with (125)I-Iothalamate clearance, creatinine was measured with a modified Jaffe method on Dimension RxL (Dade-Behring, Dudingen, Switzerland), cystatin C was determined by particle enhanced turbidimetric immunassay (PETIA; Dako, Glostrup, Denmark). Bias, precision and diagnostic accuracy of the two GFR estimates were assessed with Bland-Altman method and receiver-operating characteristics (ROC) analysis. The latter was performed at a GFR cut-off of 60 ml/min/1.73 m2. RESULTS: The cystatin C based GFR estimate normalized to a body surface area of 1.73 m2 exhibited a bias of -4.7 ml/min/1.73 m2, the 95% limits of agreement were -25.5-16 ml/min/1.73 m2 with an AUC of 0.87. The MDRD estimates obtained from the original creatinine revealed biased results. Thus, non-constant recalibration of creatinine was done. Recalibrated creatinine gave an MDRD GFR estimate with a bias of 1.7 ml/min/1.73 m2. The limits of agreement were -23.1-26.4 ml/min/1.73 m2. ROC analysis revealed an AUC 0.8 and was not significantly different from the cystatin C based GFR estimate. CONCLUSIONS: In renal transplant recipients, the cystatin C based GFR estimate exhibits similar diagnostic characteristics like the simplified MDRD formula. In contrast to cystatin C measurement, recalibration of creatinine might be necessary before implementing the simplified MDRD formula into clinical routine.

Adult↗

Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children.

Heparin-induced thrombocytopenia (HIT), a well-known side effect of heparin therapy, occurs with an incidence of 1-2% in certain pediatric patient groups. In affected children, HIT markedly increases the risk of venous and arterial thromboembolism. The use of alternative anticoagulation with danaparoid, lepirudin and argatroban in adults and children has demonstrated to be safe and could reduce morbidity and mortality also in affected pediatric patients. Thus, in children and neonates, an early diagnosis and accurate management is crucial to avoid the deleterious consequences of HIT. This review article will focus on the presentation of HIT in neonates and children. It reviews the pathophysiology of HIT and it summarizes epidemiological data. Finally important diagnostic and therapeutic issues are discussed.

Anticoagulants↗

Rapid, accurate and non-invasive detection of cerebrospinal fluid leakage using combined determination of beta-trace protein in secretion and serum.

BACKGROUND: beta-Trace protein (Btp) has been proposed as a valuable marker of cerebrospinal fluid (CSF) leakage overcoming the drawbacks of beta-2-transferrin (B-2Tr) determination. However, there is still controversy about the appropriate cut-offs to be used (range 0.35-6 mg/L). The aim of the study was to evaluate cut-offs of Btp determination for detection CSF leakage. Further, we assessed whether the Btp secretion to serum ratio (Btp-sec/ser-ratio) would add diagnostic value. METHODS: Prospective study in patients with suspected CSF leakage. Quantitative determination of Btp in secretion and serum (Dade-Behring) and qualitative measurement of B-2-Tr in secretion and serum. Results were assessed in view of clinical data. Cut-offs and diagnostic characteristics were determined by ROC analysis. RESULTS: A total of 176 samples were assessed originating from 105 patients. In 43 samples CSF leakage could be confirmed. Sensitivity of B-2-Tr was 84%, specificity amounted to 100%. The area under the curve (AUC) for Btp-measurement in secretion was 0.98. At a cut-off of 0.68 mg/L, sensitivity was 100% and specificity 91%. At a cut-off of 1.11 mg/L, the specificity was 100% with a sensitivity of 93%. The Btp-sec/ser-ratio has an AUC of 0.99. Combining a 0.68 mg/L cut-off in secretion with a Btp-sec/ser-ratio cut-off of 4.9 reveals a sensitivity of 99% and a specificity of 100%. CONCLUSIONS: Btp is a rapid and accurate marker for the presence of CSF leakage. Combining measurement of Btp in secretion together with determination of the Btp-sec/ser-ratio enhances the diagnostic characteristics of the Btp assay. Determination of Btp in both serum and secretion is thus recommended.

Adult↗

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 54x10(9)/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.

Anticoagulants↗

An automated 'bio-intact' PTH assay: a step towards standardisation and improved correlation with parathyroid function in renal disease.

BACKGROUND: Most methods for the determination of parathyroid hormone (PTH) show cross-reactivity with N-truncated forms of PTH. The analytic and diagnostic value of a recently developed automated PTH test without this cross-reactivity was examined. METHODS: The PTH levels of 73 patients undergoing hemodialysis were compared using the 'bio-intact' PTH (Nichols Institute Diagnostics) and 3 'intact' PTH tests (from Nichols, Roche Elecsys and Diagnostics Corporation DPC). Further, the (non 1-84) PTH fragment and the PTH ratio (bio-intact PTH/(non 1-84) PTH) were calculated. All results were then correlated with biochemical bone markers (bone-specific alkaline phosphatase and bone collagen C-terminal telopeptides in serum). RESULTS: 'Bio-intact' PTH values were lower than the PTH results generated by the 'intact' PTH assays. Results of all PTH tests were closely correlated (r=0.96-0.98, p<0.01). Correlations with biochemical bone markers were high (r=0.31-0.63, p<0.01), but no significant association between the PTH ratio and all other tests (r=-0.2 to 0.03) was found. CONCLUSIONS: In stable hemodialysis patients, the different PTH tests show a similar correlation with the bone markers. It is however desirable to measure PTH with assays devoid of any cross-reaction for a better comparability. In this study, the PTH ratio was not correlated with biochemical bone markers; the use of this ratio requires further investigation.

Aged↗

The predictive characteristics of D-dimer testing in outpatients with suspected venous thromboembolism: a Bayesian approach.

BACKGROUND: Despite the widespread use of quantitative methods to measure D-dimer, clinical decisions commonly are based only on binary test information (positive/negative). This study aimed to determine the significance of quantitative D-dimer results in the evaluation of venous thromboembolism (VTE) by means of a differentiated Bayesian approach. METHODS: Prospective study in 118 outpatients referred for workup of suspected pulmonary embolism (n = 75) or deep vein thrombosis (n = 43). The sensitivity and specificity of D-dimer results obtained by DD VIDAS (Biomerieux, France), STA Liatest (Diagnostica Stago, France), and D-dimer plus (Dade, US) were assessed for five different cut-offs. Further, predictive values and multilevel likelihood ratios were calculated in order to assess the operative test characteristics in excluding or confirming VTE. RESULTS: At a cut-off of 500 ng/ml and pretest probabilities < 47%, the VIDAS provides a negative predictive value (NPV) > 95%, whereas a positive predictive value (PPV) > 95% is obtained in patients with a D-dimer > 10,000 ng/ml and pretest probabilities > 50%. At a cut-off of 500 ng/ml and pretest probabilities < 33%, the Liatest exhibits a NPV > 95%, whereas a PPV > 95% is obtained in patients with a D-dimer >10,000 ng/ml and pretest probabilities > 37%. Finally, with the D-dimer plus, a NPV > 95% is seen at a cut-off of 150 ng/ml and pretest probabilities < 30%, whereas a PPV > 95% is obtained at a cut-off > 1000 ng/ml and pretest probabilities > 67%. CONCLUSIONS: D-dimer measurements in outpatients cannot only allow for exclusion but, in some situations, also for confirmation of venous thromboembolism. It is therefore advisable to conduct a quantitative interpretation of D-dimer results.

Aged↗

Quantitative monitoring of BCR--ABL transcript--suggestion of a simplified approach considering inaccuracy of measurement and calibration.

According to standard-protocols, real time quantitative RT-PCR (RQ-PCR) for quantification of BCR-ABL fusion transcripts in CML patients is performed with the construction of a standard curve for each run, each sample is analyzed at least in duplicate and 10-40 ml peripheral blood are processed. This approach is appropriate for a research laboratory, but is not suitable for a routine laboratory setting. We show that the calibration curve based on the common 5 dilution standards (between 10 and 10(6) copies) is strongly influenced by the large variability of the measurements below 100 copies of the gene. In other words, including a standard with 10 copies is a source of error, which cannot be reduced through the construction of a standard curve with each run. Adding additional dilutions between 10 and 100 copies to the standard curve, the variance of the obtained curve is much reduced. As a conclusion, it is unnecessary to construct a calibration curve with each run since only negligible inaccuracy of calibration is added to the inaccuracy of measurement. Running of the samples in duplicate seems unnecessary since the inaccuracy of the method can be correctly estimated. Finally, we propose a standardized collection and isolation of total RNA from only 2.5 ml blood using an integrated system, which allows RNA stabilization for up to 5 days and provides snapshots of BCR-ABL fusion transcripts with higher accuracy than with non-stabilized blood samples.

Calibration↗