Berndt Zur

A novel hemoglobin, Bonn, causes falsely decreased oxygen saturation measurements in pulse oximetry.

BACKGROUND A 4-year-old boy and his father exhibited low oxygen saturation measured transcutaneously by pulse oximetry, a finding that could not be confirmed by arterial blood gas analysis. Both patients exhibited slight hemolysis in their blood, and the boy had a microcytic anemia. There was no evidence of hypoxemia or methemoglobinemia. Despite the normal results from the arterial blood gas analysis, a right-to-left-shunt was assumed in the boy until a cardiology examination excluded this diagnosis. Sleep apnea syndrome was suspected in the father and treated with nocturnal positive pressure respiration based on the low oxygen saturation values obtained with pulse oximetry. Only after consultation with our laboratory was a hemoglobin variant suspected and investigated. METHODS We performed hemoglobin protein analysis by HPLC, electrophoretic separation, and spectrophotometry and DNA sequence analysis of the alpha-globin gene. RESULTS Both HPLC chromatographic separation and alkaline electrophoresis revealed a unique hemoglobin peak. In both patients, alpha-globin gene sequencing revealed a mutation resulting in a histidine-to-aspartatic acid substitution at position alpha87. The low oxygen saturation measurement by pulse oximetry was due to hemoglobin Bonn oxyhemoglobin having an absorption peak at 668 nm, near the 660 nm measured by pulse oximeters. CONCLUSION Hemoglobin Bonn is a novel hemoglobin variant of the proximal alpha-globin that results in falsely low oxygen saturation measurements with pulse oximetry.

The prognostic value of acute and chronic troponin elevation after transcatheter aortic valve implantation

AIMS Myocardial injury occurs frequently following transcatheter aortic valve implantation (TAVI). The aim of this study was to assess timing, predictors, and prognostic value of periprocedural myocardial injury and chronic troponin elevation after TAVI. METHODS AND RESULTS Two hundred and seventy-six patients (logistic EuroSCORE 26.6±17.1%) underwent transvascular TAVI. Troponin, CK-MB, and NT-proBNP levels were measured before and after TAVI (1 hr, 4 hrs, 24 hrs, 48 hrs, 72 hrs, seven days, three, and six months). Myocardial injury (according to VARC-2 recommendation defined as ΔTroponin ≥15x URL) occurred in 143/276 patients (51.8%) during the first 72 hours following TAVI. Use of a self-expanding prosthesis (p=0.02), coronary artery disease (p=0.04), higher left ventricular ejection fraction (LVEF) (p<0.001), and procedure time (p<0.001) were independent predictors for the development of myocardial injury after TAVI. Thirty-day (4.2% vs. 6.1%; p=0.48) and one-year mortality (19.4% vs. 26.5%; p=0.15) were not related to the incidence of periprocedural myocardial injury. However, patients with chronic troponin elevation after TAVI had an increased one-year mortality risk (HR 4.5, 95% CI: 2.0-10.0; p<0.001). CONCLUSIONS Myocardial injury defined as ΔTroponin ≥15x URL after TAVI seems to be a procedure-related issue without impact on 30-day and one-year survival. However, monitoring of post-procedural troponin might be useful for prognostication after TAVI.

Factorial structure of the 20-item Toronto Alexithymia Scale in a large sample of somatoform patients

Although a strong association between alexithymia and somatization has been postulated in numerous studies, no systematic study has investigated the psychometric properties of the 20-item Toronto Alexithymia Scale (TAS-20) in a sample of patients with somatoform disorder yet. The purpose of this study was to ensure a valid assessment by the German version of the TAS-20 in somatoform samples. We investigated whether the original three-factor model proposed by Bagby et al. (1994a), which is widely used in clinical research and practice, is replicable in a large sample of somatoform patients (n=806). Using confirmatory factor analysis (CFA) the goodness-of-fit of the originally proposed factor structure was compared to three factor models generated with exploratory factor analysis (EFA) and other factorial solutions derived from the literature. Our results demonstrate that the original three-factor model is not replicable in somatoform patients. Instead, the four-factor model by Franz et al. (2001b) described the data best. However, none of the models met all criteria of confirmatory factor analysis. Our results indicate that the three-factor model is not robust in the German version of the TAS-20. At this state of research we recommend to use the TAS-20 sum-score as a measure of alexithymia in somatoform patients in clinical practice.

Effects of the flavonol quercetin and α -linolenic acid on n -3 PUFA status in metabolically healthy men and women: a randomised, double-blinded, placebo-controlled, crossover trial

Increased dietary intake and tissue status of the long-chain n-3 PUFA, EPA and DHA, is associated with cardiovascular benefits. Epidemiological and animal studies suggest that concomitant nutritive intake of flavonoids may increase the conversion of α-linolenic acid (ALA) to longer-chain n-3 fatty acids EPA and DHA. We investigated the effects of increased ALA intake on fatty acid composition of serum phospholipids and erythrocytes in metabolically healthy men and women and whether fatty acid profiles and ALA conversion were affected by regular quercetin intake or sex. Subjects (n 74) were randomised to receive at least 3·3 g/d ALA with either 190 mg/d quercetin (ALA+quercetin) or placebo (ALA+placebo) in a double-blinded, placebo-controlled, crossover trial with 8-week intervention periods separated by an 8-week washout period. A total of seven subjects dropped out for personal reasons. Data from the remaining sixty-seven subjects (thirty-four males and thirty-three females) were included in the analysis. Both interventions significantly increased serum phospholipid ALA (ALA+placebo: +69·3 %; ALA+quercetin: +55·8 %) and EPA (ALA+placebo: +37·3 %; ALA+quercetin: +25·5 %). ALA + quercetin slightly decreased DHA concentration by 9·3 %. Erythrocyte ALA and EPA significantly increased with both interventions, whereas DHA decreased. Fatty acid composition did not differ between sexes. We found no effect of quercetin. Intake of 3·6 g/d ALA over an 8-week period resulted in increased ALA and EPA, but not DHA, in serum phospholipids and erythrocytes. Neither quercetin supplementation nor sex affected the increment of ALA and relative proportions of n-3 PUFA in serum phospholipids and erythrocytes.

Melatonin concentration in umbilical cord blood depends on mode of delivery

BACKGROUND AND AIMS Melatonin (MT) is rapidly transferred from the maternal to fetal circulation in humans. There is little knowledge about factors which influence the MT concentration (MTc) in the umbilical cord (UC) blood during delivery. The aim of our study was to evaluate the MT status in the UC blood according to the time and mode of delivery. SUBJECTS AND METHODS Blood samples from umbilical artery (UA) and vein (UV) were collected from spontaneous vaginal deliveries (SVD, n=122) and cesarean section deliveries (CSD, n=188). MTc was measured using a commercially available radioimmunoassay. RESULTS The MTc was not significantly different between UA and UV blood both at daytime and at nighttime (p=0.216 and p=0.440, respectively). Both in UA and in UV, the MTc was significantly higher at nighttime than at daytime (p<0.0001). Compared with the CSD group, MTc in the SVD group was significantly higher both at night- and daytime (p<0.05). MTc both in UA and in UV was found to be not significantly different between patients with and without risk factors for stress including pregnancy complications (e.g., preeclampsia) and intrapartum complications (e.g., emergency section, pathological doppler, and pathological cardiotocography) (p>0.05). CONCLUSION Our study revealed for the first time that MTc both in UA and in UV depends on modus of labor. In agreement with other studies, we found a clear circadian MT rhythm in the UC blood of neonates. The results of our study may suggest to a physiological role of MT at the onset of labor.

Influence of Apnea-induced Hypoxia on Catecholamine Release and Cardiovascular Dynamics

Prolonged breath-hold causes complex compensatory mechanisms such as increase in blood pressure, redistribution of blood flow, and bradycardia. We tested whether apnea induces an elevation of catecholamine-concentrations in well-trained apneic divers.11 apneic divers performed maximal dry apnea in a horizontal position. Parameters measured during apnea included blood pressure, ECG, and central, in addition to peripheral hemoglobin oxygenation. Peripheral arterial hemoglobin oxygenation was detected by pulse oximetry, whereas peripheral (abdominal) and central (cerebral) tissue oxygenation was measured by Near Infrared Spectroscopy (NIRS). Exhaled O2 and CO2, plasma norepinephrine and epinephrine concentrations were measured before and after apnea.Averaged apnea time was 247±76 s. Systolic blood pressure increased from 135±13 to 185±25 mmHg. End-expiratory CO2 increased from 29±4 mmHg to 49±6 mmHg. Norepinephrine increased from 623±307 to 1 826±984 pg ml-1 and epinephrine from 78±22 to 143±65 pg ml-1 during apnea. Heart rate reduction was inversely correlated with increased norepinephrine (correlation coefficient -0.844, p=0.001). Central (cerebral) O2 desaturation was time-delayed compared to peripheral O2 desaturation as measured by NIRSabdominal and SpO2.Increased norepinephrine caused by apnea may contribute to blood shift from peripheral tissues to the CNS and thus help to preserve cerebral tissue O2 saturation longer than that of peripheral tissue.

METHOD COMPARISON FOR CA 15-3, CA 19-9, AND CA 125 DETERMINATION USING THE NEW LOCI TECHNIQUE OF DIMENSION VISTA 1500 AND IMMULITE 2000 XPI

We performed method comparison for the tumor markers CA 15-3, CA 19-9, and CA 125 measured by luminescent oxygen channeling immunoassay technology on the Dimension Vista 1500 and by classic luminescence technology on the Immulite 2000 XPI. Within-day and total imprecision were determined according to Clinical and Laboratory Standards Institute (CLSI) guidelines using three serum pools at different clinically relevant levels. In addition, parallel measurements on both systems were performed in a total of 738 routine serum samples (133 CA 15-3, 395 CA 19-9, and 210 CA 125). Total imprecision of serum pools for CA 15-3 ranged between 4.6% and 5.9%, for CA 19-9 between 4.4% and 7.8%, and for CA 125 between 3.3% and 4.3%. Marker values determined within the measurement range of both systems correlated well with each other (R = 0.88 for CA 15-3, R = 0.93 for CA 19-9, and R = 0.96 for CA 125). Slopes between the Vista and the Immulite method were 0.96 for CA 125, 0.72 for CA 15-3, and 0.87 for CA 19-9, indicating lower values for CA 15-3 and CA 19-9 when measured by the Vista method. This was particularly obvious for CA 19-9 levels in the lower measuring range of <100 U/mL (R = 0.85; slope 0.73).

A 14-Year-Old Boy with Chronic Cyanosis, Mild Anemia, and Limited Physical Resistance to Stress

In April 1997, a then 4-year-old boy suddenly fell ill with fever, cough, fatigue, and poor physical resistance to stress. Marked cyanosis of the lips and the nail beds was noted. During his 3-week hospital stay, mycoplasmosis of the lung and a respiratory syncytial virus infection were diagnosed by the detection of high-titer Mycoplasma agglutinins in serum samples and positive test results for the presence of respiratory syncytial virus in nasopharyngeal secretions. In addition, incipient exogenous allergic alveolitis was suspected because of the presence of budgerigars and cockatiels in the boys home and the finding of serum positivity for IgG precipitin. The boys condition gradually improved with cefuroxime and clarythromycin treatment and oxygen therapy. α1-Antitrypsin deficiency and cystic fibrosis were excluded. Because the patients oxygen saturation failed to improve during sleep and at times dropped to well below 90%, a cardiology examination was performed, and a cardiac defect was ruled out. The reticulocyte count and the curve of the absorption spectrum of oxyhemoglobin and deoxyhemoglobin were within the reference interval. Hemogram results were as follows: leukocytes, 5500/μL (reference interval, 5100–12 900/μL); hemoglobin, 11 g/dL (reference interval, 10.7–13.9 g/dL); thrombocytes, 319 000/μL (reference interval, 200 000–445 000/μL); mean corpuscular volume, 78 fL (reference interval, 74–89 fL); mean corpuscular hemoglobin, 26 pg (reference interval, 24.5–31 pg). At the same time, hemoglobin electrophoresis excluded hemoglobinopathy. One year later, the boy was electively readmitted to the pediatric clinic for assessment of continuous intermittent low oxygen saturation. Exogenous allergic alveolitis was excluded after bronchoalveolar lavage; sarcoidosis was also ruled out. Slight cyanosis of the lips was once again noted, however. Pulse oximetry showed normal oxygen saturation >93% during the day, but oxygen saturation repeatedly dropped to as low as 85% during sleep. Oxygen administration improved saturation immediately to >95%. These fluctuations in oxygen …

Evaluation of the appropriate time period between sampling and analyzing for automated urinalysis

Introduction Preanalytical specifications for urinalysis must be strictly adhered to avoid false interpretations. Aim of the present study is to examine whether the preanalytical factor ‘time point of analysis’ significantly influences stability of urine samples for urine particle and dipstick analysis. Materials and methods In 321 pathological spontaneous urine samples, urine dipstick (Urisys™2400, Combur-10-Test™strips, Roche Diagnostics, Mannheim, Germany) and particle analysis (UF-1000 i™, Sysmex, Norderstedt, Germany) were performed within 90 min, 120 min and 240 min after urine collection. Results For urine particle analysis, a significant increase in conductivity (120 vs. 90 min: P < 0.001, 240 vs. 90 min: P < 0.001) and a significant decrease in WBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), RBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), casts (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and epithelial cells (120 vs. 90 min P = 0.610, 240 vs. 90 min P = 0.041) were found. There were no significant changes for bacteria. Regarding urine dipstick analysis, misclassification rates between measurements were significant for pH (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), leukocytes (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), nitrite (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), protein (120 vs. 90 min P < 0.001, 240 vs. 90 min P<0.001), ketone (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), blood (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), specific gravity (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and urobilinogen (120 vs. 90 min, P = 0.031). Misclassification rates were not significant for glucose and bilirubin. Conclusion Most parameters critically depend on the time window between sampling and analysis. Our study stresses the importance of adherence to early time points in urinalysis (within 90 min).

Role of Neutrophil CD64 Index as a Screening Marker for Late-Onset Sepsis in Very Low Birth Weight Infants.

Introduction The role of CD64 in late onset sepsis (LOS) in preterm infants has been described in several studies. Aim of this study was to investigate whether CD64 expression is increased in the days before clinical manifestation of LOS. Methods Patients with birth weight below 1,500g were eligible for study participation. During routine blood sampling CD64 index was determined between day of life 4 and 28. Patients were allocated to one of four groups: (1) blood-culture positive sepsis, (2) clinical sepsis, (3) symptoms of infection without biochemical evidence of infection, or (4) patients without suspected infection. Kinetics of CD64 expression were compared during a period before and after the day of infection in the respective groups. Results 50 infants were prospectively enrolled and allocated to each group as follows: group (1) n = 7; group (2) n = 10; group (3) n = 8; and group (4) n = 25. CD64 index was elevated in 57% of patients in group (1) at least two days before infection. In contrast only 20% in the clinical sepsis group and 0% in group (3) had an elevated CD64 index in the days before infection. 10 of the 25 patients in the control group (4) presented increased CD64 index values during the study period. Conclusions The CD64 index might be a promising marker to detect LOS before infants demonstrate signs or symptoms of infection. However, larger prospective studies are needed to define optimal cut-off values and to investigate the role of non-infectious inflammation in this patient group.