Cerebrospinal Fluid Protein Concentration in Healthy Older Japanese Volunteers

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in the older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in healthy older Japanese volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL). Conclusions: The reference interval of CSF-TP in the older population should be reconsidered for the precise diagnosis of neurological emergencies.

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Cerebrospinal Fluid Protein Concentration in Japanese Healthy Older Volunteers

10.20944/preprints202105.0558.v1 ◽

2021 ◽

Author(s):

Tatsuya Yoshihara ◽

Masayoshi Zaitsu ◽

Kazuya Ito ◽

Ryuzo Hanada ◽

Eunhee Chung ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Protein Concentration ◽

Reference Range ◽

Asian Population ◽

Reference Limit ◽

Older Volunteers ◽

The Mean ◽

Upper Reference Limit ◽

Age Range ◽

Cerebrospinal Fluid Protein

The concentration of cerebrospinal fluid total protein (CSF-TP) is important for the diagnosis of neurological emergencies. Recently, some Western studies have shown that the current upper reference limit of CSF-TP is quite low for older patients. However, little is reported about the concentration of CSF-TP in older Asian population. In this study, we retrospectively analyzed the CSF-TP concentrations in Japanese healthy older volunteers. CSF samples in 69 healthy Japanese volunteers (age range: 55–73 years) were collected by lumbar puncture, and the data of CSF were retrospectively analyzed. The mean (standard deviation) CSF-TP was 41.7 (12.3) mg/dL. The older group (≥ 65 years old) had higher CSF-TP concentration than the younger group (55–64 years old). The 2.5th percentile and 97.5th percentile of CSF-TP were estimated as 22.5 and 73.2 mg/dL, respectively, which were higher than the current reference range in Japan (10–40 mg/dL).

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Intra- and interindividual variability of carbohydrate-deficient transferrin, γ-glutamyltransferase, and mean corpuscular volume in teetotalers

Clinical Chemistry ◽

10.1093/clinchem/44.10.2120 ◽

1998 ◽

Vol 44 (10) ◽

pp. 2120-2125 ◽

Cited By ~ 30

Author(s):

Anders Helander ◽

Erling Vabö ◽

Klas Levin ◽

Stefan Borg

Keyword(s):

Mean Corpuscular Volume ◽

Iron Concentration ◽

Reference Interval ◽

Reference Intervals ◽

Mean Value ◽

Corpuscular Volume ◽

Mean Values ◽

Reference Limit ◽

Carbohydrate Deficient Transferrin ◽

The Mean

Abstract Blood samples for determination of the biochemical alcohol markers carbohydrate-deficient transferrin (CDT) in serum, γ-glutamyltransferase (GGT) in serum, and erythrocyte mean corpuscular volume (MCV) were collected once every 1–2 weeks over ∼5 months from 10 female and 4 male teetotalers. Mean values for serum CDT (using the CDTectTM assay) ranged from 9.9 to 29.4 units/L (median, 14.2 units/L), and the highest results were obtained in the women. The mean values for serum GGT ranged from 0.15 to 0.49 μkat/L (median, 0.30 μkat/L, or 18 U/L) except for one woman with a very high mean of 3.07 μkat/L. For MCV, the mean values ranged from 79.5 to 91.5 fL. Two women showed several CDT results above the upper reference limit (mean values, 27.6 and 29.4 units/L, respectively); however, their GGT and MCV values fell within the reference intervals. One of these women exhibited an increased total transferrin concentration (mean value, 5.38 g/L), which was possibly related to the use of oral contraceptives and/or a low serum iron concentration. When the CDTect value was expressed relative to total transferrin, a ratio within the reference interval was observed for this woman but not for the other woman with increased CDTect values. The present study demonstrates a considerable variation between individuals in CDT, GGT, and MCV without drinking any alcohol. The results also show that these baseline values are fairly constant over time within the same individual.

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Definition of the upper reference limit of glycated albumin in blood donors from Italy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0179 ◽

2017 ◽

Vol 56 (1) ◽

Cited By ~ 20

Author(s):

Chiara Bellia ◽

Martina Zaninotto ◽

Chiara Cosma ◽

Luisa Agnello ◽

Bruna Lo Sasso ◽

...

Keyword(s):

Blood Donors ◽

Glycated Albumin ◽

Specific Reference ◽

Reference Limit ◽

Percentile Method ◽

The Mean ◽

Definition Of ◽

Upper Reference Limit ◽

Mean Glucose

AbstractBackground:Glycated Albumin (GA) has been proposed as a short-term indicator of glycemic homeostasis. The aim of this study is to describe the distribution of GA in a large sample of blood donors from Italy to evaluate whether demographic features, namely age and sex, could influence GA levels and define specific reference limits.Methods:The study included 1334 Italian blood donors. GA was measured using an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The upper reference limit (URL) was calculated using the non-parametric percentile method.Results:A modest, although significant, increase of GA was observed in relation to age (p<0.001), especially in males, where the differences were more pronounced (p<0.001 in males, p=0.003 in females). Slight differences were documented based on sex (12% [11.3–12.8] in males; 12.2% [11.4–13.1] in females; p=0.01). After excluding individuals with fasting plasma glucose ≥7 mmol/L, the calculated GA URL was 14.5% (95% CI: 14.3–14.7). Subjects with GA>14.5% presented a mean age of 48.4±12.2 years, 66.7% were males and the mean glucose was 6.88±2.5 mmol/L.Conclusions:GA in Caucasians shows a similar increasing trend at older ages documented in other ethnicities. The definition of the URL in this population could be useful for both clinical studies, which will clarify the role of GA for diagnosing and monitoring diabetes, and will encourage the introduction of GA in clinical practice.

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Disappearance Rate of Catecholamines, Total Metanephrines, and Neuropeptide Y from the Plasma of Patients after Resection of Pheochromocytoma

Clinical Chemistry ◽

10.1093/clinchem/47.6.1075 ◽

2001 ◽

Vol 47 (6) ◽

pp. 1075-1082 ◽

Cited By ~ 43

Author(s):

Eric Grouzmann ◽

Marc Fathi ◽

Michel Gillet ◽

Antoine de Torrenté ◽

Claudia Cavadas ◽

...

Keyword(s):

Neuropeptide Y ◽

Plasma Concentrations ◽

Amperometric Detection ◽

Reference Interval ◽

Diagnostic Value ◽

Relative Increase ◽

Time Curve ◽

Reference Limit ◽

Upper Reference Limit ◽

Total Sulfate

Abstract Background: Plasma free metanephrines are a more reliable analyte to measure than catecholamines for the biochemical diagnosis of pheochromocytomas. We hypothesized that the long persistence of total (sulfate-conjugated plus free) metanephrines in the blood might have a significant diagnostic value. Methods: We measured plasma concentrations of catecholamines and total metanephrines (sulfate-conjugated plus free forms) by HPLC with amperometric detection, and neuropeptide Y (NPY) by an amplified ELISA in seven patients before and after removal of their pheochromocytomas. The results for catecholamine, total metanephrines, and NPY in each patient were analyzed for up to 120 min, starting from the time of tumor vessel clamping. The persistence of analytes was quantified as the area under the concentration–time curve over 120 min. Results: On the basis of the upper reference limit for each variable, plasma free norepinephrine (NE) and epinephrine (E) concentrations were increased preoperatively in at least one sample in seven and six patients, respectively. Total normetanephrine (NMN) and metanephrine (MN) were increased in all samples in seven and six patients, respectively. NPY was increased 2- to 465-fold. After removal of the tumor, MN and NMN showed a higher average relative increase above the upper limit of the reference interval than NE and E (P = 0.05), whereas NPY was intermediate. The persistence of increased values was significantly shorter for catecholamines than for metanephrines. The half-life estimated by nonlinear regression was 12.3 ± 7.8 min for NPY. Significant correlations were observed among NE, E, NMN, MN, and NPY concentrations, but parent markers (E and MN or NE and NMN) did not appear significantly intercorrelated. Conclusions: A larger increase and a longer persistence of total metanephrines (reflecting predominantly sulfo-conjugated metanephrines) than catecholamines and NPY in plasma may contribute to their greater diagnostic accuracy in pheochromocytoma.

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Cerebrospinal Fluid Protein Concentrations in Children: Age-related Values in Patients without Disorders of the Central Nervous System

Clinical Chemistry ◽

10.1093/clinchem/46.3.399 ◽

2000 ◽

Vol 46 (3) ◽

pp. 399-403 ◽

Cited By ~ 23

Author(s):

Daniel Biou ◽

Jean-François Benoist ◽

Claire Nguyen-Thi ◽

Xuan Huong ◽

Philippe Morel ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Reference Values ◽

Total Protein ◽

Age Groups ◽

Term Neonates ◽

Age Related ◽

The Central Nervous System ◽

Set Up ◽

Age Range ◽

Cerebrospinal Fluid Protein

Abstract Background: The published reference values for cerebrospinal fluid (CSF) total protein concentrations in children suffer from two major drawbacks: (a) the age-related range often is too broad when applied to the steeply falling concentrations in early infancy; and (b) no values have been published for widely used dry chemistry methods. Methods: We conducted a 2-year retrospective survey of CSF results obtained in a children’s hospital with a dry chemistry-based method set up on the Vitros 700 analyzer. Results: The data related to ambulatory children up to 16 years of age and term neonates with no clinical or biological signs of brain disease (n = 1074). Seven age groups with significantly different CSF protein values were identified, and their age-related percentiles (5th, 50th, and 95th) were determined. On the basis of the upper 95th percentile, from age 0 to 6 months the CSF protein concentrations fell rapidly from 1.08 to 0.40 g/L. A plateau (0.32 g/L) was reached from age 6 months to 10 years, followed by a slight increase (0.41 g/L) in the 10–16 years age range. Conclusions: These results imply that CSF total protein concentrations in the pediatric setting, particularly in infants, must always be interpreted with regard to narrow age-related reference values to avoid false-positive results.

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Choice of Statistical Tools for Outlier Removal Causes Substantial Changes in Analyte Reference Intervals in Healthy Populations

Clinical Chemistry ◽

10.1093/clinchem/hvaa208 ◽

2020 ◽

Vol 66 (12) ◽

pp. 1558-1561 ◽

Cited By ~ 1

Author(s):

Peter E Hickman ◽

Gus Koerbin ◽

Julia M Potter ◽

Nicholas Glasgow ◽

Juleen A Cavanaugh ◽

...

Keyword(s):

Statistical Methods ◽

Population Studies ◽

Large Population ◽

Large Body ◽

Reference Interval ◽

Reference Intervals ◽

Outlier Removal ◽

Reference Limit ◽

Statistical Measures ◽

Upper Reference Limit

Abstract Background Reference intervals are an important aid in medical practice as they provide clinicians a guide as to whether a patient is healthy or diseased. Outlier results in population studies are removed by any of a variety of statistical measures. We have compared several methods of outlier removal and applied them to a large body of analytes from a large population of healthy persons. Methods We used the outlier exclusion criteria of Reed-Dixon and Tukey and calculated reference intervals using nonparametric and Harrell-Davis statistical methods and applied them to a total of 36 different analytes. Results Nine of 36 analytes had a greater than 20% difference in the upper reference limit, and for some the difference was 100% or more. Conclusions For some analytes, great importance is attached to the reference interval. We have shown that different statistical methods for outlier removal can cause large changes to reported reference intervals. So that population studies can be readily compared, common statistical methods should be used for outlier removal.

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Rapid determination of serum myoglobin with a routine chemistry analyzer

Clinical Chemistry ◽

10.1093/clinchem/39.4.653 ◽

1993 ◽

Vol 39 (4) ◽

pp. 653-658 ◽

Cited By ~ 6

Author(s):

A J Bakker ◽

D A Boymans ◽

D Dijkstra ◽

J P Gorgels ◽

R Lerk

Keyword(s):

Predictive Value ◽

Rapid Determination ◽

Reference Interval ◽

High Dose ◽

Reference Limit ◽

Hook Effect ◽

Upper Limit ◽

Upper Reference Limit ◽

Serum Myoglobin

Abstract A turbidimetric immunoassay system (Turbitime system, Behringwerke AG) allows rapid determination of myoglobin in serum. We adapted the reagents for this myoglobin assay (Turbiquant myoglobin) for use with a Hitachi 717 analyzer. No high-dose hook effect was observed up to 15,000 micrograms/L. Interassay CVs were 4.6% (mean = 72.0 micrograms/L; n = 9) and 2.5% (mean = 365.6 micrograms/L; n = 11). The calibration curve was stable for at least 1 month. Hemolysis did not interfere, and turbidity from lipemia interfered only when absorbance exceeded 2.0 A. Results of this method (y) correlated well with those by the Turbitime method (y = 1.256x - 44.1 micrograms/L; n = 91; r = 0.991) and by a commercially available radioimmunoassay (Byk-Sangtec; y = 0.739x - 42.2 micrograms/L; n = 94; r = 0.991). The upper limit (95th percentile) of the reference interval for myoglobin was estimated at 57.9 micrograms/L. The positive predictive value for results of myoglobin at admission was 89% with this upper reference limit and 99% with 100 micrograms/L, whereas the negative predictive value was about 60% for both limits.

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Routine α-Amylase Assay Using Protected 4-Nitrophenyl-1,4-α-d-maltoheptaoside and a Novel α-Glucosidase

Clinical Chemistry ◽

10.1093/clinchem/46.5.644 ◽

2000 ◽

Vol 46 (5) ◽

pp. 644-649 ◽

Cited By ~ 14

Author(s):

Klaus Lorentz

Keyword(s):

Amylase Activity ◽

Reference Method ◽

Reference Interval ◽

Lag Phase ◽

Reference Limit ◽

Independent Constant ◽

Increased Sensitivity ◽

Upper Reference Limit ◽

Manual Performance ◽

Age And Sex

Abstract Background: In contrast to numerous methods for measuring α-amylase activity, the approved IFCC reference method offers an invariable time-independent constant product pattern, thus avoiding possibly changing stoichiometric calculations. However, reference methods do not lend themselves to routine use, so that such methods need to be modified. Methods: Ethylidene-blocked 4-nitrophenylmaltoheptaoside (EPS-G7) is degraded to glucose and 4-nitrophenol in a coupled assay with a bacterial α-glucosidase under the following measurement conditions: 3.5 mmol/L EPS-G7, 7.1 kU/L α-glucosidase, 70 mmol/L sodium chloride, 1 mmol/L calcium chloride, 50 mmol/L HEPES, pH 7.15, at 37 °C. The increase of absorbance is continuously monitored for 3 min at 405 nm after a lag phase of 2 min. Results: Catalytic concentrations up to 15-fold higher than the upper reference limit can be determined without dilution. Precision studies in manual performance show CVs of 1.4–2.6% (within-run) and 1.9–2.8% (day-to-day). There was no interference from 100 mmol/L glucose, 30 mmol/L triacylglycerols, 610 μmol/L bilirubin, and 2.95 g/L hemoglobin. The method closely correlates with other chromogenic assays. The preliminary 0.95 reference interval for adults, not dependent on age and sex, is 33.6–96.2 U/L. Conclusion: The procedure is a robust adaptation of the reference method to routine use at 37 °C with increased sensitivity, fewer interferences, and reduced cost.

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Albumin and calcium reference interval using healthy individuals and a data-mining approach

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563220944204 ◽

2020 ◽

Vol 57 (5) ◽

pp. 373-381 ◽

Cited By ~ 2

Author(s):

N Jassam ◽

A Luvai ◽

D Narayanan ◽

D Turnock ◽

G Lee ◽

...

Keyword(s):

Metrological Traceability ◽

Reference Interval ◽

Reference Population ◽

Reference Intervals ◽

Healthy Individuals ◽

Reference Limit ◽

Common Reference ◽

Age Related ◽

Upper Reference Limit ◽

Analytical Platforms

Background Harmonization of reference intervals for analytes that have a sound calibration and metrological traceability is a widely recommended practice. The UK Pathology Harmony has recently harmonized reference intervals for calcium and albumin. In this study, we have determined the reference intervals for calcium and albumin on the UK’s most commonly used analytical platforms. Method A prospective reference population of healthy individuals was recruited according to the IFCC CRIDL criteria. A second indirect population was collected from 14 primary care setting and measured in laboratories using various analytical platforms and methods (Roche, Abbott, Beckman and Siemens analytical platforms). Results In total, 299 subjects were recruited; the central 95th centile values for calcium for three out of four analytical platforms were in a close agreement with UK Pathology Harmony reference intervals of 2.2–2.6 mmol/L. Reference intervals of BCG methods from both cohorts and irrespective of analytical platforms were higher for both lower and upper reference limits than those for BCP. In comparison, the indirect study showed an age-related variation. The younger population reference intervals varied by up to 5.7% at the lower reference limit and up to 12% at the upper reference limit compared with Pathology Harmony reference intervals, and the older population showed a variation of up to 14% at both limits. Conclusion While calcium reference intervals can be a subject for harmonization, albumin reference intervals studied showed large variation which is unsupportive of embracing a common reference interval for albumin.

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Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0152 ◽

2017 ◽

Vol 56 (1) ◽

Cited By ~ 5

Author(s):

Anke Heida ◽

Anneke C. Muller Kobold ◽

Lucie Wagenmakers ◽

Koos van de Belt ◽

Patrick F. van Rheenen

Keyword(s):

Characteristic Curve ◽

Reference Value ◽

Reference Interval ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Children ◽

Healthy Controls ◽

Reference Limit ◽

School Aged Children ◽

Activated Neutrophils ◽

Upper Reference Limit

AbstractBackground:Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls.Methods:In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5–19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (InflamarkResults:The upper reference limit in healthy children was 0.75 μg/g (90% confidence interval: 0.30–1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 μg/g [interquartile range (IQR) 2.5–11.6] compared to healthy controls [0.22 μg/g (IQR<0.22); p<0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 μg/g (sensitivity 93%; specificity 97%).Conclusions:Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from non-organic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers.

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