Effects of Intra-and Interindividual Variation on the Appropriate Use of Normal Ranges

1974 ◽  
Vol 20 (12) ◽  
pp. 1535-1542 ◽  
Author(s):  
Eugene K Harris

Abstract Normal ranges based on the distribution of single samples from a large number of individuals reflect both intra- and interindividual variation. If the average ratio of these two sources of variation is small, then, assuming gaussian distributions, the conventional normal range will usually include a larger than expected proportion of an individual's distribution of values. When the average ratio exceeds 1.4, the normal range will include a proportion either larger or smaller than expected, depending on whether the individual's variability is less than or greater than average intra-individual variation. Investigation of multivariate normal regions in certain cases where calculations are feasible produced similar results. With these numerical guidelines, data from recent blood-chemistry studies indicate that conventional normal ranges are likely to be less sensitive than desired to significant changes in an individual's biochemical state. This analysis supports the continued development and use of cumulative (in time) systems for reporting laboratory test results for individuals.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4199-4199
Author(s):  
Sabine Geiter ◽  
Markus Graf ◽  
Elin Tschokert ◽  
Agnes Veyradier ◽  
Martine Wolf ◽  
...  

Abstract Abstract 4199 INTRODUCTION In recent years, diagnostic tests for ADAMTS-13 and respective autoantibodies became available and are routinely used to support thrombotic thrombocytopenic purpura (TTP) diagnosis and therapy. ADAMTS-13 abnormalities have also been described in other pathological situations such as liver cirrhosis (Uemura, 2008), sepsis- induced DIC (Ono, 2006) or inflammatory bowel disease (Feys, 2009), where the relationship between ADAMTS13 parameters and state of disease is less clear than in TTP. A clear-cut distinction between normal and pathologic levels of ADAMTS-13 parameters (activity, antigen and autoantibodies) is only available in most TTP, with ADAMTS-13 activity levels < 10% and antibody titers well above normal levels. Pathological ranges for other diseases are not yet well defined. As normal ranges for ADAMTS-13 levels seem to be very broad, differentiation between normal and pathologic levels in cases other than TTP will depend on the size of the population used to establish the normal range and presumably also on age, gender, and likely also on other parameters present in this population. AIM The aim of this study was therefore to establish normal values for ADAMTS-13 parameters by analyzing normal populations in five different European laboratories using the same commercial assays. Material and Methods ADAMTS-13 autoantibodies were measured using the TECHNOZYM®ADAMTS-13 INH ELISA (anti-IgG). ADAMTS-13 activity and antigen concentrations were measured using TECHNOZYM®ADAMTS-13 ELISA, a combined assay for activity and antigen. Samples were frozen citrated plasma samples used in the respective laboratories as normal controls (approximately 40 in each laboratory; all together 193 normal controls). RESULTS The normal range for anti-ADAMTS-13 IgG was compared between the 5 different labs. For ADAMTS-13 INH, the median in these different populations varied between 6 and 9 U/ml which is well below the previously defined borderline value of 12 – 15 U/ml in this assay. The median for all samples was 6.7 U/ml; the number of “false-positives” (>15U/ml) varied from 5 to 10%. To analyze a possible age dependency, three groups were considered : <30 y.o., 31-50 y.o. and >50 y.o. No age dependent differences between these groups could be found (p>0.6). No significant differences were either found between male and female controls (p=0.55). For ADAMTS-13 activity and antigen only data from 140 normal subjects and 60 TTP patients are currently available. For normal subjects, the median for ADAMTS-13 activity was 103%, for antigen 101%. Both parameters showed a wide distribution of values between 53% and 205% for activity and 34% and 217% for antigen. In comparison, the median values in TTP patients were significantly lower (activity 12%, antigen 49%). Conclusion We can show that a substantial variation in normal values for ADAMTS-13 activity and antigen exists in normal subjects, while the range for ADAMTS-13 autoantibodies is rather narrow. All values in normal subjects are well separated from those obtained in TTP patients. The broad range of ADAMTS-13 activity and antigen in normal subjects has to be considered when these parameters are measured in diseases other than TTP. Disclosures: Geiter: Technoclone GmbH: Employment. Graf:Technoclone GmbH: Employment. Tschokert:Technoclone GmbH: Employment. Vetr:Technoclone GmbH: Employment.


1972 ◽  
Vol 18 (3) ◽  
pp. 244-249 ◽  
Author(s):  
Eugene K Harris ◽  
David L DeMets

Abstract When healthy individuals are surveyed to estimate the "normal range" of some measured variable, generally only a single determination of the variable is obtained for each person. The distribution of such values reflects intra-individual variations, (including analytic deviations) as well as the differences among individuals with respect to such parameters as mean or variance. These underlying sources of variation have been expressed in a conditional probability model from which general equations have been derived showing the effects of these variations on the shape parameters (skewness and kurtosis) of a single-sample distribution. These results may help to explain the shape of a given distribution. More generally, they imply that methods of calculating normal ranges would benefit from a study of various mathematical transformations that could convert distributions of almost any shape to approximately gaussian form. Data from recent blood-chemistry studies are used to compare observed shape statistics with those calculated from the model.


2019 ◽  
Vol 12 (2) ◽  
pp. 53-58
Author(s):  
S. Singh ◽  
BR Sharma ◽  
M. Bhatta ◽  
N. Poudel

Aim: The aim of this study is to assess the anteroposterior diameter of brainstem (midbrain, pons and medulla) of normal Nepalese people to establish normal ranges and to correlate the measurement with pa­tient’s age and gender. Method: The study is a cross-sectional prospective study which is per­formed in Gandaki Medical College, Pokhara. The data is collected over the period of 5 months from May 2018 to September 2018. The data of total 103 patients are collected who underwent (Magnetic Resonance Imaging) MRI head. Measurements of sagittal diameter at predefined levels i.e. distance between upper border of pons to midway between superior and inferior colliculi (A) for midbrain, distance between an­terior surface of pons to the floor of fourth ventricle (B) for pons and anteroposterior diameter perpendicular to the long axis of medulla just above the posterior kink at cervicomedullary junction for medulla ob­longata were made and noted. Result: The mean anteroposterior diameter of midbrain, pons and me­dulla oblongata was found to be 1.7048 ± 0.12 cm, 2.27 ± 0.13cm and 1.3 ± 0.088 cm respectively. The average ratio of sagittal diameter of pons to sagittal diameter of midbrain was 1.34 ± 0.099 cm and average ratio of sagittal diameter of pons to medulla oblongata was 1.75 ± 0.123 cm. Conclusion: There was no statistically significant correlation of the sagittal diameter of midbrain, pons and medulla with patient’s gender. The sagittal diameter of brainstem reached maximum at the age 20 and stopped increasing. The sagittal diameter of midbrain and medulla ob­longata decreased slightly after the age of 50 and decreased significant­ly after the age of 70. There was no decrease in the sagittal diameter of pons after age.


PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 622-623
Author(s):  
Robert Ellis

Objective. Lumbar punctures in children are generally performed in a flexed position. Published normal ranges for cerebrospinal fluid (CSF) opening pressure require measurement in an extended position, and flexion is known to increase lumbar CSF pressure. This study sought to determine a normal range (mean ± 2 SD) for lumbar CSF opening pressure measured in a flexed lateral decubitus position in children. Methods. Opening pressure was measured in 33 children receiving diagnostic lumbar punctures or prophylactic intrathecal chemotherapy. Measurements were performed in a flexed lateral decubitus position. Patients with medical conditions affecting CSF pressure were excluded. Results. Opening pressure (mean ± SD) was 19.0 ± 4.4 cm H2O. Opening pressure was not significantly affected by patient age or sex. Intrathecal chemotherapy and sedation also did not affect CSF pressure. Conclusions. The normal range for lumbar CSF opening pressure measured in a flexed lateral decubitus position in children is 10 to 28 cm H2O.


1992 ◽  
Vol 73 (3) ◽  
pp. 1040-1046 ◽  
Author(s):  
G. M. Barnas ◽  
D. Stamenovic ◽  
K. R. Lutchen

We evaluated the effect of pulmonary edema on the frequency (f) and tidal volume (VT) dependences of respiratory system mechanical properties in the normal ranges of breathing. We measured resistance and elastance of the lungs (RL and EL) and chest wall of four anesthetized-paralyzed dogs during sinusoidal volume oscillations at the trachea (50–300 ml, 0.2–2 Hz), delivered at a constant mean airway pressure. Measurements were made before and after severe pulmonary edema was produced by injection of 0.06 ml/kg oleic acid into the right atrium. Chest wall properties were not changed by the injection. Before oleic acid, EL increased slightly with increasing f in each dog but was independent of VT. RL decreased slightly and was independent of VT from 0.2 to 0.4 Hz, but above 0.4 Hz it tended to increase with increasing flow, presumably due to the airway contribution. After oleic acid injection, EL and RL increased greatly. Large negative dependences of EL on VT and of RL on f were also evident, so that EL and RL after oleic acid changed two- and fivefold, respectively, within the ranges of f and VT studied. We conclude that severe pulmonary edema changes lung properties so as to make behavior VT dependent (i.e., nonlinear) and very frequency dependent in the normal range of breathing.


2016 ◽  
Vol 73 (9) ◽  
pp. 877-880 ◽  
Author(s):  
Andrijana Kulic ◽  
Zorica Cvetkovic ◽  
Vesna Libek

Introduction. A bleeding syndrome in the setting of primary hyperfibrinolysis in a prostate cancer patient is only 0.40? 1.65% of cases. The laboratory diagnosis of primary hyperfibrinolysis is based on the increase of biomarkers like D-dimer, fibrinogen split products, plasminogen, and euglobulin lysis test. These tests are not specific for primary hyperfibrinolysis. We reported a rare case of hemorrhagic syndrome caused by primary hyperfibrinolysis as the first clinical symptom of metastatic prostate cancer. Case report. A 64-year-old male was admitted to our hospital with large hematomas in the right pectoral and axillary areas (20 x 7 cm), right hemiabdomen (30 x 30 cm) and the left lumbal area, (25 x 5 cm). The patient had no subjective symptoms nor used any medication. Initial coagulation testing, prothrombin time (PT), and activated partial thromboplastin time (APTT) were within the normal range, while fibrinogen level was extremely low (1.068 g/L) (normal range 2.0?5.0) and the D-dimer assay result was high 1.122 mg/L (normal range < 0.23). The results obtained by rotation thrombelastometry pointed to primary fibrinolysis. Further clinical and laboratory examination indicated progressive malignant prostate disease. First line treatment for the patient was a combined administration of tranexamic acid (3 x 500 mg iv) and transfusion of ten units of cryoprecipitate (400 mL). Next day, fibrinolytic function measurements by rotation thrombelastometry were within the normal ranges. Fibrinogen level was normalized within two days (2.4 g/L). There were no newly developed hematomas. Conclusion. This case report shows primary hyperfibrinolysis with bleeding symptoms, which is an uncommon paraneoplastic phenomenon within expanded prostate malignancy. Rotation thrombelastometry in this severe complication helped to achieve the prompt and proper diagnosis and treatment.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4010-4010
Author(s):  
Emma Arthur ◽  
Andrea Cortese Hassett ◽  
Franklin A. Bontempo

Abstract Closure times (CTs) have replaced the limitations of the previous testing methods. However, the clinical utility of detecting abnormal CTs remains poorly defined, with the differential diagnosis including von Willebrand’s disease (vWD), aspirin or NSAIDs, uremia, liver disease, or congenital defects. Ristocetin cofactor (RCoF) measures the functional activity of the vW molecule and when low, most often suggests vWD. CTs are frequently done in patients suspected by history of having vWD with some laboratories preferring to perform the collagen/epinephrine (Col/Epi) CT alone, while others additionally include the collagen/ADP (Col/ADP) CT. METHODS: We analyzed 1480 consecutive CTs from a large reference laboratory done on a PFA-100 (Dade-Behring) and correlated the CTs with RCoF levels done on a BCS analyzer (Dade-Behring). Normal ranges were: Col/Epi CT 84-175 sec.; Col/ADP CT 65-117 sec.; RCoF 0.5-1.5 U/ml. Calculated means for CT of ≥ 300 sec. used a level of 300. TABLE Of the 260 studies with abnormal closure times, 131 (50%) had normal RCoF values, 47 (18%) were high and 18 (32%) were low. All studies with low RCoFs had at least one abnormal CT with 78/82 (95%) having both CTs prolonged, 2/82 (≫2%) with a long Col/EPI only, and 2/82 (≫2%) with a long Col/ADP only. Mean CTs in patients with low RCoFs and both CTs abnormal were 252 seconds for Col/EPI and 174 seconds for Col/ADP, both well above the upper limits of the normal range. Mean CTs in patients with low RCoFs and one abnormal CT were 180 seconds for Col/EPI and 123 seconds for Col/ADP, both just slightly above the upper limits of the normal range. CONCLUSIONS: These findings suggest that when RCoF is low, both Col/EPI and Col/ADP CTs are prolonged, usually markedly, and the chances that a low RCoF will be missed is low, particularly if both CTs are used. RESULTS: Total CTs analyzed: 1480 No.≥ 1 Abnormal CT 260/1480 (18%) Number (%) Both CTs Abnormal Col/Epi ONLY Abnormal Col/ADP ONLY Abnormal Total Abnormal CTs 260 (100%) 203 (78%) 42 (16%) 15 (6%) Total Low RCoFs 82 (100%) 78 (95%) 2 (≈2%) 2 (≈2%)


1983 ◽  
Vol 40 (4) ◽  
pp. 420-425 ◽  
Author(s):  
W. Roscoe Miller III ◽  
Albert C. Hendricks ◽  
John Cairns Jr.

Wytheville strain rainbow trout (Salmo gairdneri) were used in an 11-mo study designed to establish normal ranges for several hematological and blood chemistry characteristics. Two nonparametric techniques, percentile estimation and tolerance interval, were used and produced comparable ranges to those based on the Gaussian distribution. Serum glucose levels appeared to coincide with the condition of the gonads; low glucose levels corresponded with approximate spawning times at the hatchery. Total serum protein and gonadal condition were similarly related. High variability of the serum enzymes LDH and SGOT was partially explained by a positive linear relationship between enzyme activity and acclimation temperatures. In addition to physiological significance, determination of normal ranges for rainbow trout has promise in diagnosis of pathological, disease, and toxicant-induced stresses.


1973 ◽  
Vol 44 (3) ◽  
pp. 185-196 ◽  
Author(s):  
G. E. Levin ◽  
C. K. McPherson ◽  
Patricia M. Fraser ◽  
D. N. Baron

1. Plasma aspartate transaminase and alkaline phosphatase activities were measured weekly for approximately 30 weeks in a group of healthy males and females. 2. The magnitude of variation of the enzyme activities within any individual was studied with respect to four criteria: (a) the individual's normal range, (b) the normal range calculated for each sex separately, (c) the clinically accepted normal ranges, (d) the distribution of a derived term which excluded the variation of the predominant enzyme activities between individuals, and the between-batch variation. 3. The main conclusions were: (a) Normal variation for both these enzymes is small. (b) Most of the variability is contributed by analytical variation. Within-individual variation is very small, this applying particularly to the male subjects' activity of alkaline phosphatase, and the aspartate transaminase activity of female subjects. (c) Elevation of the two enzyme activities above clinical normal ranges was infrequent, never of great magnitude, and occurred almost exclusively in males. When elevations of enzyme activity occurred, they tended to be associated either with particular males, or to occur on certain weeks. (d) When the latter effects were allowed for, and a new set of criteria calculated, the resulting ‘abnormal’ values now appeared to be more randomly distributed.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
MohammadBagher Shamsi ◽  
Korosh Veisi ◽  
Loghman Karimi ◽  
Javad Sarrafzadeh ◽  
Farid Najafi

Background. Although there are frequent studies about normal range of thoracic kyphosis, there is still a controversy about the exact values of this curve. In nine reported studies on 10 to 20 years of age boys, the value ranged from 25.1° to 53.3°. Objective for the Study. The aim of the present research was investigation of normal ranges of thoracic kyphosis in school children in Kermanshah, western Iran. Methods. 582 male students aged 13 to 18 years old using cluster random sampling were recruited from schools in Kermanshah city, 97 students for each age. Thoracic curves were measured using the flexicurve method. Results. Mean thoracic kyphosis for whole population was 35.49° SD 7.83 and plus or minus two standard deviations ranged from 19.83° to 51.15°. It increased gradually from 13 to 16 and then there was a little decrease to 18 years. Mean values for each age (13–16) were 13 (34.41 SD 7.47°), 14 (34.86 SD 8.29°), 15 (35.79 SD 7.93°), 16 (36.49 SD 7.85°), 17 (35.84 SD 8.33°), and 18 (35.55 SD 7.07°). Conclusions. Our results are in agreement with previous reports and can be used as normal values for local and regional purposes.


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