Reference distributions for alpha2-macroglobulin: a comparison of a large cohort to the world's literature

The lack of satisfactory methods for quantifying serum levels and a credible reference material has limited bedside use of serum alpha(2)-macroglobulin (alpha2M) measurements. Great strides have been made in the last few years. The remaining barrier to more relevant and cost effective use of serum protein data for diagnosis and prognosis is the availability of reliable reference intervals from birth to old age for both males and females. A total of 40 publications reporting reference intervals have been identified that meet the criteria used in our prior five studies, and these have been analyzed statistically. On average, previous small studies of these individual proteins agree with our life-long reference ranges over their constrained age ranges. This meta-analysis provides support for our reference ranges and places them in the perspective of previous publications.     

Reference distributions for the positive acute phase proteins, alpha1-acid glycoprotein (orosomucoid), alpha1-antitrypsin, and haptoglobin: a comparison of a large cohort to the world's literature

Limiting bedside use of positive acute phase protein measurements (alpha1-acid glycoprotein (orosomucoid), alpha1-antitrypsin, and haptoglobin) has been the lack of satisfactory methods for quantifying serum levels and a credible reference material. Great strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis is the availability of reliable reference intervals from birth to old age for both males and females. Sixty publications reporting reference intervals have been identified which meet the criteria used in our prior two studies, and these have been analyzed statistically. Previous small studies of these individual proteins agree on average, over their constrained age ranges, with our life-long reference ranges. This meta-analysis provides support for our reference ranges and places them in the perspective of previous publications.     

Reference distributions for serum iron and transferrin saturation: a comparison of a large cohort to the world's literature

The appropriate clinical use of serum iron and transferrin saturation (TSAT) requires satisfactory reference intervals from birth to old age, and for males and females. This study identified 54 publications from 1974 to 2001 that met the criteria used in three prior meta-analyses, and these were analyzed statistically. A summary of our review is presented along with our reference population data on these measurements. This analysis places previous publications in perspective and suggests possible reasons for the observed differences. Previous studies of the individual analytes, serum iron, transferrin, and TSAT values agree with the reference ranges presented in this study, although the entire experience over time and between sexes has not been available before. Our 95% reference ranges are somewhat broader than those of the smaller studies, but they agree well with those of the larger ones.     

Reference distributions for complement proteins C3 and C4: a practical, simple and clinically relevant approach in a large cohort

The two serum proteins of the complement cascade in the highest concentrations, C3 and C4, respond to various conditions in much the same manner as do other positive acute-phase proteins. A major difference is that they are relatively sluggish in response to cytokine drive, requiring several days rather than hours to be detectably elevated by serial measurements. As with other acute-phase proteins, there are many processes that up- or down-regulate synthesis, including infection or inflammation, hepatic failure, and immune-complex formation. Clinicians may find it difficult to distinguish among these processes, because they often occur simultaneously. The situation is further complicated by genetic polymorphism, with rare instances of markedly reduced synthesis and circulating levels, and consequent vulnerability to infection. C3 and C4 are measured for clinical purposes to help define certain rheumatic and immunologically mediated renal diseases. Interpreting the measured blood levels of these two components requires one to consider the intensity of the inflammatory drive, the timing of the suspected clinical process, the production of complement-consuming immune complexes, and the possible existence of benign circumstances. In this fifth article in a series, reference ranges for serum levels of two complement proteins (C3 and C4) are examined. The study is based on a cohort of over 55,000 Caucasian individuals from northern New England, who were tested in our laboratory in 1994-1999. Measurements were standardized against certified reference material (CRM) 470/reference preparation for proteins in human serum (RPPHS), and analyzed using a previously described statistical approach. Individuals with unequivocal laboratory evidence of inflammation (C-reactive protein of 10 mg/L or higher) were excluded. Our results show that the levels of C3 and C4 change little during life and between the sexes, except that they increase slightly and then fall after age 20 in males and at about age 45 in females. When values were expressed as multiples of the age- and gender-specific median levels, the resulting distributions fitted a log-Gaussian distribution well over a broad range. When patient data are normalized in this manner, the distribution parameters can be used to assign a centile corresponding to an individual's measurement, thus simplifying interpretation.     

Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison of a large cohort to the world's literature

Limiting the clinical utility of apolipoproteins AI (apo AI) and B (apo B) and the apo B/AI ratios until the last decade has been the lack of satisfactory methods for quantifying serum levels and credible reference materials. Great technological strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis has been the availability of widely recognized reliable reference intervals from birth to old age for both males and females. A total of 82 publications reporting reference intervals have been identified that meet most of the same inclusion criteria used in our prior six studies. These have been analyzed statistically and compared to similar studies, i.e., sufficient number, listed subject criteria, method, and reference material, in general terms. Published smaller studies with constrained age ranges, agree on average with our large series of life-long reference intervals that range from less than one year to over 80 years. This study was performed to assess the degree of agreement between smaller reference interval studies to our large population analysis. This meta-analysis provides support and reassurance that many of the smaller reference intervals published previously fall within reasonable limits of out large population.     

Reference distributions for immunoglobulins A,G, and M: A comparison of a large cohort to the world's literature

Clinical interpretation of immunoglobulin measurements requires accurate and precise assays and widely accepted reference preparations, as well as reliable age- and gender-specific reference ranges. This last requirement, the topic of numerous publications, has not been addressed adequately. By a combination of computerized and hand searching of the literature from 1961 to 1997, we identified 109 publications presenting IgA, IgG, and/or IgM reference data in healthy individuals. After eliminating studies that lacked appropriate clinical, statistical, or reference material information, data from the 17 acceptable studies were converted to a common reference material, CRM 470/RPPHS. When median levels from our recently published large cohort study are superimposed on these published medians, they fall within the ranges of reported medians. The widths of published 95 percentile reference ranges (where each individual's health was verified) were also found to agree closely with the reference range widths found in our data (where inclusion was based on the reported diagnosis). The current combined study of narrowly applied reference ranges validates our recently published age- and gender-specific reference data for immunoglobulins A, G, and M. Those new data can now be considered as a source of reliable reference ranges to be used by laboratories when interpreting immunoglobulin measurements. J. Clin. Lab. Anal. 12:371–377, 1998. © 1998 Wiley-Liss, Inc.     

Reference distributions for serum iron and transferrin saturation: a practical,simple, and clinically relevant approach in a large cohort

The principal considerations driving iron status evaluation are clinical concern for anemia and the possibility of iron-storage disease. Most often, the circulating levels of transferrin (or total iron binding capacity) and serum iron are measured and the percentage of transferrin saturation (TSAT) is then computed. Optimally, reference ranges for these analytes should exclude the effects of the acute phase response, nutritional status, estrogen effect, specific genetic disorders, liver disease, and blood transfusion. The current study reports reference ranges for serum iron and TSAT within a cohort of over 55,000 Caucasians from northern New England, tested in our laboratory between 1994 and 1999. Measurements were standardized against serum reference material (SRM) 937 (for iron) and certified reference material (CRM) 470 (also called reference preparation for proteins in human serum (RPPHS)) (for transferrin), and analyzed using a previously published approach. Individual cases with evidence of inflammation (C-reactive protein > or =10 mg/L), or iron overload (TSAT >80% for males and >70% for females) or serum iron values <5 micro mol/L, were removed. Among the referent individuals, iron and TSAT levels rose slightly until the teen years, at which time levels in males increased while those in females remained essentially constant. Between 20 and 70 years of age, males had 10-15% higher iron levels and 15-20% higher TSAT levels than females. When values were expressed as multiples of the age- and gender-specific median levels, the serum iron and TSAT observations fit log-Gaussian distributions reasonably well from the 20th to 99th centile, and the 10th to the 99th centile, respectively. After normalization, the Gaussian parameters can be used to assign a corresponding centile to an individual's measurement, simplifying interpretation. These data provide new and more detailed reference ranges for serum iron and TSAT.     

Cystatin C reference values and aging

OBJECTIVES: The aim of this study was to determine the reference values for serum cystatin C (CysC) with a particular focus on the effect of aging. DESIGN AND METHODS: The study was performed on a consecutive series of subjects (258 men and 396 women). Laboratory parameters and a detailed personal and family medical history were collected. RESULTS: CysC showed a significant correlation with age in both sexes, which was confirmed with multivariate linear regression after adjustment for SCr (serum creatinine). Age-related reference intervals were established for cystatin C (<45 years, <0.95 mg/L and >45 years, <1.20 mg/L). CONCLUSIONS: The use of CysC reference values adjusted for age should be carefully taken into consideration.     

Intra-individual variation in the concentrations of IgA, IgG, IgM, and complement component C3 in serum of a normal adult population.

A recent study [Clin. Chem. 22, 1635 (1976)] reported intra-individual variation in 10 serum proteins to be much smaller than interindividual variation. We report results of a similar study involving about 700 apparently healthy adults in whom we estimated the relative magnitude of the intra- and interindividual variation in serum IgA, IgG, IgM and complement component C3. Specimens were collected from each subject weekly for as long as 10 weeks (average, four weeks). The four serum proteins were quantitated by radial immunodiffusion by the maximal-diffusion technique. Traditional 95% reference intervals were computed relative to WHO reference preparations for the immunoglobulins. For C3, the reference interval was computed relative to a commercial reference preparation. We, too, found the ratios of intra-individual to interindividual variation for adults to be so small that the traditional reference intervals do not have the assumed diagnostic sensitivities. Furthermore, these ratios did not change after dividing the study population into subgroups according to sex and age; evidently such subgrouping do not improve the diagnostic sensitivity. The relatively small intra-individual variations were also observed at the extremes of protein concentration ranges.     

昆明地区健康人群血清胱抑素C参考区间调查

目的调查昆明地区健康人群血清胱抑素C（CystatinC,Cys-C）水平,建立实验室诊断参考区间。方法应用颗粒增强免疫透射比浊法测定130例健康受检者血清胱抑素C浓度;用SPSS16．0软件对检测结果进行统计学处理。结果130例健康受检者的血清胱抑素C浓度与性别、体重指数无关。受检者的血清胱抑素c浓度1-60岁年龄段血清胱抑素C的浓度水平一致,95％的可信区间为0．500-1．120mg／L;大于60岁年龄段95％的可信区间0．670-1．290mg／L。结论胱抑素C的参考范围在不同年龄人群中是不一致的,昆明市健康人群1-60岁血清胱抑素C的参考范围是0．500-1．120rag／L;大于60岁年龄段95％的可信区间为0．670-1．290mg／L,因此在临床上评价肾小球滤过率应建立适宜的参考范围。     

辛伐他汀对急性心肌梗死患者基质金属蛋白酶和高敏C反应蛋白的影响

目的：探讨辛伐他汀对急性心肌梗死患者血浆高敏C反应蛋白和基质金属蛋白酶-9的影响。方法：60例急性心肌梗死患者随机分为两组,常规治疗组和辛伐他汀治疗组,治疗前后分别测定血浆高敏C反应蛋白和基质金属蛋白酶-9的浓度,并与对照组比较。结果：急性心肌梗死患者血浆高敏C反应蛋白和基质金属蛋白酶-9的测定值高于健康对照组（P〈0.05）;辛伐他汀治疗组治疗后血浆高敏C反应蛋白和基质金属蛋白酶-9的测定值分别低于治疗前水平（P〈0.05）。结论：辛伐他汀通过抗炎等机制对防治急性心肌梗死患者早期动脉粥样硬化及稳定斑块起着重要的作用。     

The existing interim consensus reference ranges and the future approach.

The release of the reference material for serum proteins, CRM 470/RPPHS, in 1993, has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. However, conversion to the new reference material has resulted in significant changes in reference values for some proteins. The establishment of new reference ranges is currently in progress; in the interim, several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies that were already undertaken.     

威海地区1300名健康成人血清胱抑素c参考值调查

目的：调查分析威海地区健康成人血清胱抑素C（Cysc）水平,探讨不同性别、年龄、健康成人Cysc水平的差异,并建立不同性别、不同年龄组威海地区健康成人Cysc的参考范围。方法：本研究为大样本流行病学调查,采用分层、随机抽样的原则,于2012年7月---2013年12月,从来我院健康查体的11600名18-90岁健康人群按年龄、性别分层进行随机抽样共有1300人入选,并对其进行体检和血清Cysc水平检测,剔除离群个体数据后共1295名受试者入选,其中男648人,女647人。采用t检验和方差分析比较不同性别及年龄组间Cysc水平的差异,LSD法进行组间的两两比较。采用百分位数（P2.5～P97.5）建立不同性别、不同年龄组健康成人血清Cysc的参考范围。结果：不同性别、不同年龄组间Cysc水平差异有统计学意义。根据方差分析结果,分别按性别、年龄建立参考范围,其中男性18-50岁、51-60岁、61-90岁参考范围分别是0.64～1.18、0.66～1.39、0.67～1.51mg/L;女性18-40、41-50、51-60、61-90岁参考范围分别是0.51～1.03、0.56～1.05、0.57～1.14、0.69～1.55mg／L。结论：初步建立了威海地区健康成人血清Cysc的参考范围,对临床医生判断和评估患者的肾功能有很好的参考价值。     

忻州地区健康成人血清总蛋白、清蛋白及清蛋白/球蛋白比值的参考范围调查

目的 了解并建立忻州地区健康成人血清总蛋白(TP)、清蛋白(ALB)以及清蛋白/球蛋白比值(A/G)的参考范围.方法 对2008年10月至2011年12月间来该院检查的4 014例健康成人血清总蛋白(TP)、清蛋白(ALB)进行测定,并计算A/G比值;对检测结果进行统计分析,计算参考值范围.结果 该地成人血清总蛋白(TP)、清蛋白(ALB)及A/G比值的平均值分别为71.51 g/L、43.66 g/L和1.60;参考范围分别为:TP(59.96～83.06)g/L,ALB(36.91～50.41)g/L,A/G(1.11～2.09);不同性别、不同年龄段人群之间血清TP、ALB、A/G水平存在不同程度的差异.结论 不同地区人群的血清总蛋白、清蛋白及A/G比值水平也不尽相同,各地区、实验室应建立当地不同性别、不同年龄段的参考范围,以供临床对检验结果的诊断作出正确判断.     

Evaluation of a quick test for C‐reactive protein in a pediatric emergency department

Objective. C‐reactive protein (CRP) is a reliable laboratory test that is useful in distinguishing between viral and bacterial infection. Although widely used, blood sampling and the need for a well‐organized laboratory are limiting factors. Recently, a rapid test for serum CRP (QuickRead CRP) has been developed that can use both venous and capillary blood. The aim of this study was to use QuickRead CRP in our Pediatric Emergency Department and to compare this method with the standard laboratory determination (CRP‐lab). Material and methods. All children with fever were given a quick CRP test simultaneously with venous (CRP‐V) and capillary blood samples (CRP‐C). A total of 127 children were included in the study (median age 2.5 years). Results. The QuickRead CRP test had an excellent correlation with the standard biochemical determination (CRP‐lab). More importantly, there was no difference in determination of CRP in the venous and capillary blood samples. Finally, there was no significant intra‐assay variability. Conclusions. The QuickRead CRP test is easy to use, provides reliable results and reduces the need for antibacterial therapy.     

Cystatin C as a marker of GFR--history, indications, and future research

OBJECTIVE: To summarize recent knowledge on the small molecular weight protein cystatin C (cys-C) and its use as a marker of the glomerular filtration rate (GFR). METHODS: A multinational expert meeting was held in April 2002 in Marburg, Germany. Contributors summarized their main findings. CONCLUSIONS: Cys-C is at least equal if not superior to serum creatinine as a marker of GFR. The independence from height, gender, age, and muscle mass is advantageous. Select patient groups such as children, the elderly, and patients with reduced muscle mass benefit in particular.     

半胱氨酸蛋白酶抑制剂C参考范围的设立及在糖尿病肾功能评价中的作用

目的确立本实验室半胱氨酸蛋白酶抑制剂C（CysC）的参考范围和界定肾功能不全分期的CysC水平。方法检测120名健康体检者CysC水平,确立本实验室CysC参考范围。选取200例血肌酐（Cr）为45～1001μmol／L的样本,进行血清Cr、尿素（Urea）、尿酸（UA）和CysC检测,了解CysC与cr的相关性;测定100例糖尿病患者的CysC,了解其CysC水平。结果本实验室健康人群CysC参考范围为≤1．02mg／L,CysC与cr的相关系数（r）为0．7346,CysC水平在2．18—3．15mg／L和≥3．16mg／L可分别作为界定。肾功能不全氮质血症期和尿毒症期的衡量标准,糖尿病患者的CysC水平明显高于一般人群。结论CysC是衡量糖尿病患者肾功能状况的理想指标。     

Reference ranges of electrolyte and anion gap on the Beckman E4A, Beckman Synchron CX5, Nova CRT, and Nova Stat Profile Ultra

The widespread use of ion-selective electrode causes the reference range of the anion gap (AG) to be lowered from 8-16 to 3-11 mmol/l. The use of the outdated reference range (8-16 mmol/l) leads to the misinterpretation of the value of the anion gap. To interpret the anion gap accurately, one must use an analyzer-specific reference range. This study established the reference ranges of the electrolyte and anion gap in four ion-selective electrode analyzers. We collected clotted and lithium-heparinized blood from 124 healthy volunteers. We determined the electrolyte in the Beckman E4A (serum), Beckman Synchron CX5 (serum), and Nova CRT (serum and plasma). The anion gap was calculated from the formula: [Na(+)-(Cl(-)+HCO3(-))]. Blood sodium, potassium and bicarbonate were determined using the Nova Stat Profile Ultra. We used the plasma chloride from the Nova CRT to calculate the value of the anion gap in the Nova Stat Profile Ultra. We established the reference ranges using the non-parametric percentile estimation method. Accuracy and precision of the electrolyte performances obtained from all analyzers were acceptable. Reference values of serum and plasma sodium, potassium, and chloride were similar in all analyzers. The value of blood sodium obtained from the Nova Stat Profile Ultra was slightly higher than the values for the serum and plasma sodium obtained from the other analyzers. The bicarbonate ranges obtained from the Nova analyzers were higher than the values obtained from the Beckman analyzers. For the anion gap, the reference ranges in this study were low but similar to other studies (3-11 mmol/l) using ion-selective electrode. However, our reference ranges were lower than the previous reference ranges obtained from the continuous-flow analyzer (8-16 or 9-18 mmol/l) incorporated with flame photometry and colorimetry techniques.     

血清半胱氨酸蛋白酶抑制剂C与肾脏病理改变的相关性分析

目的通过探讨半胱氨酸蛋白酶抑制剂C(Cys C)、血清肌酐(SCr)与一些重要肾脏病理改变及临床指标的相关性,为Cys C的临床应用提供更多的循证医学证据。方法随机抽取260例肾活检患者,分别分析患者的Cys C、SCr与肾脏病理损害程度(全球硬化、肾小管萎缩、间质纤维化)评分、年龄、血红蛋白(Hb)的相关性。将患者按全球硬化0～4分划分为5组;按肾小管萎缩0～3分划分为4组;按间质纤维化0～3分划分为4组,再分别比较各病理组间Cys C及SCr的变化。结果 Cys C与SCr、全球硬化、肾小管萎缩、间质纤维化、年龄均呈明显正相关(r分别为0.850、0.471、0.592、0.610、0.197,P均<0.01);SCr与全球硬化、肾小管萎缩、间质纤维化均呈明显正相关(r分别为0.501、0.595、0.607,P均<0.01),但SCr与年龄无相关性(r=0.118,P>0.05);Cys C、SCr均与Hb呈明显负相关(r分别为-0.448、-0.369,P均<0.01)。各病理组间Cys C及SCr水平差异均有统计学意义(P均<0.01),随着病理损害程度的增加,各组Cys C及SCr水平也随之增加;当病理损害程度达到1～2分(<50%)时,大多数患者Cys C水平达到或超出参考范围上限,而大多数患者SCr水平仍在参考范围内。结论 Cys C与SCr均能较好地反映患者的肾脏病理损害及肾功能状况,Cys C评价早期肾损伤的敏感性要优于SCr,但两者均存在影响因素。因此在选择评估肾功能的指标时应以患者存在的影响因素为参考,必要时可联合多项指标以提高评估肾功能的准确性。     

山西忻州地区居民血脂2项参考范围的建立

目的 了解并建立忻州地区不同年龄人群血脂2项的参考范围,规范本地区高脂血症的诊断标准,为研究本地区高脂血症、高血压、心脑血管疾病的预防和治疗提供帮助.方法 对2008年10月至2011年7月来解放军第五一七医院检查的4 474例健康人群的血清三酰甘油(TG)、总胆固醇(TC)进行测定,并分别按性别和年龄分组,对各组的检测结果进行统计分析并计算参考值范围.结果 本地人群血清TG和TC平均值分别为1.39 mmol/L和4.23 mmol/L,且女性平均值高于男性,差异有统计学意义(P<0.05);男性血清TG和TC水平随着年龄的增长而增高,然而在60岁以后会出现下降;女性血清TG和TC水平随着年龄的增长而一直增高.结论 不同地区人群的血脂水平也不尽相同,各地区、实验室应建立本地区不同性别、不同年龄组的血脂参考范围,以供临床对检验结果的诊断价值作出正确判断.