On the Estimation of the Proportion of True Recent Infections Using the BED Capture Enzyme

to be no substantive objection to implementing the sug-gestion by Favus(11)with45Ca as the tracer. However,whether a stable or a radioactive tracer is used,there is now a suitable algorithm for both men and women,requiring only a single serum sample and pro-viding results within1day.This study was supported in part by an agreement with the University of Pittsburgh,Graduate School of Public Health,by contracts with Roots,Inc.and DepoMed,Inc., by a grant from Health Future Foundation,and by Creighton University funds.References1.Nordin BEC,Need AG,Morris HA,Horowitz M,Chatterton BE,Sedgwick AW.Bad habits and bad bones.In:Burckhardt P,Heaney RP,eds.Nutritional aspects of osteoporosis’94(Proceedings of2nd International Symposium on Osteoporosis,Lausanne,May1994).Rome:Ares-Serono Symposia, 1995:1–25.2.deGrazia JA,Ivanovich P,Fellows H,Rich C.A double isotope method formeasurement of intestinal absorption of calcium in man.J Lab Clin Med 1965;66:822–9.3.Heaney RP,Recker RR.Estimation of true calcium absorption.Ann InternMed1985;103:516–21.4.Heaney RP,Recker RR.Estimating true fractional calcium absorption.AnnIntern Med1988;108:905–6.5.Ensrud KE,Duong T,Cauley JA,Heaney RP,Wolf RL,Harris E,et al.Lowfractional calcium absorption increases the risk of hip fracture in women with low calcium intake.Ann Intern Med2000;132:345–53.6.Jackson JD,Dunlevy JA.The orthogonal least squares slope estimator:interval estimation and hypothesis testing under the assumption of bivariate normality.American Statistical Association Proceedings of the Business and Economics Statistics Section1981;1:294–7.7.Barger-Lux MJ,Heaney RP,Recker RR.Time course of calcium absorption inhumans:evidence for a colonic component.Calcif Tissue Int1989;44:308–11.8.Geigy Pharmaceuticals.Documenta Geigy scientific tables,6th ed.Ardsley,NY:Geigy Pharmaceuticals,1962:538.9.Heaney RP.Evaluation and interpretation of calcium kinetic data in man.ClinOrthop1963;31:153–83.10.Heaney RP,Weaver CM,Barger-Lux J.Food factors influencing calciumavailability.In:Burckhardt P,Heaney RP,eds.Nutritional aspects of osteoporosis’94(Proceedings of2nd International Symposium on Osteo-porosis,Lausanne,May1994).Rome:Ares-Serono Symposia,1995:229–41.11.Favus M.Intestinal calcium absorption:have we absorbed enough fromresearch to have a test for the patient?J Bone Miner Res1989;4:461–2.som S,Ibbertson K,Hannan S,Shaw D,Pybus J.Simple test of intestinalcalcium absorption measured by stable strontium.BMJ1987;295:231–4.13.Sips AJAM,van der Vijgh WJF,Barto R,Netelenbos JC.Intestinal strontiumabsorption:from bioavailability to validation of a simple test representative for intestinal calcium absorption.Clin Chem1995;41:1446–50.14.Wasserman RH.Strontium as a tracer for calcium in biological and clinicalresearch.Clin Chem1998;44:437–9.15.Heaney RP.Absorbing calcium.Clin Chem1999;45:161–2.Sensitive Immunoluminometric Assay for the Detection of Procalcitonin,Nils G.Morgenthaler,*Joachim Struck, Christina Fischer-Schulz,and Andreas Bergmann(Research Department,B⅐R⅐A⅐H⅐M⅐S AG,Biotechnology Centre, D-16761Hennigsdorf/Berlin,Germany;*author for cor-respondence:fax49-3302-883-451,e-mail n.morgenthaler@ brahms.de)Procalcitonin(PCT)and other calcitonin precursors are detectable in various conditions leading to systemic in-flammatory response syndrome.Among them are pancre-atitis(1,2),burns(3),polytrauma(4),and most impor-tantly,bacterial infection(5).PCT reflects the severity of bacterial infection and has been used as a marker for the diagnosis and therapeutic monitoring of sepsis,severe sepsis,and septic shock of bacterial origin(6–10).The usual two-sided chemiluminescence assay[immunolumi-nometric assay(ILMA)]for PCT has a functional assay sensitivity(FAS)of300ng/L.This FAS is sufficient for the monitoring of septic patients in intensive care units,but the usefulness of the present ILMA in the usual hospital or outpatient setting is limited.Furthermore,except for an initial report on PCT and other calcitonin precursors in a few controls(8),it has not been possible to define the range of PCT in healthy individuals or to determine whether increased PCT exerts a pathophysiologic role (11–13).We developed a new PCT assay with aϾ30-fold lower FAS compared with the established ILMA and measured PCT values in500healthy controls.Samples were obtained from healthy blood donors(age range,18–62years;241males,259females)with no history of acute or chronic disease and with no symptoms of the common cold for the last7days.Written consent was obtained from all donors.For the PCT assay,tubes were coated with a monoclo-nal antibody specific for the katacalcin part of PCT.This antibody binds to amino acids102–111of PCT(ERDHR-PHVSM).Coating of the antibody was done for20h on polystyrene tubes(2.0␮g/tube)in0.3mL of buffer(10 mmol/L Tris-HCl,pH7.8,10mmol/L NaCl).Tubes were blocked with10mmol/L sodium phosphate buffer con-taining30q/L Karion FP,5g/L protease-free bovine serum albumin(Sigma),pH6.8,and lyophilized.A poly-clonal sheep antibody specific for the calcitonin part of PCT was used as tracer.This antibody was raised to peptide69–79(GTYTQDLNKFH)of PCT and was affini-ty-purified on a calcitonin-sulfolink column and subse-quently labeled with acridinium ester as follows:100␮g of antibody in20mmol/L sodium phosphate buffer,pH 8.0,was incubated for20min at room temperature with10␮l of acridinium ester(1g/L in acetonitrile;Hoechst AG). Labeled antibody was purified by HPLC using a Knauer hydroxyapatite column(buffer gradient,1–500mmol/L potassium phosphate,pH6.8;flow rate,0.8mL/min). PCT was measured in a coated-tube assay in which100␮L of a patient sample or calibrator was added in dupli-cate to each antibody-coated tube and incubated for30 min at room temperature;200␮L of tracer containing acridinium ester-labeled anti-PCT antibody was then added,followed by a2-h incubation at room temperature. Tubes were washed five times with2mL of standard LUMItest®washing buffer(B⅐R⅐A⅐H⅐M⅐S AG),and detec-tion was performed in a luminometer(detection time per sample,1s).This assay system was named B⅐R⅐A⅐H⅐M⅐S ProCa-S®to distinguish it from the similar LUMItest PCT®(B⅐R⅐A⅐H⅐M⅐S AG).Relative light units for the chemiluminescence assay were expressed in ng/L PCT as calculated from a calibration curve that was included in every analytical run.788Technical BriefsTo prepare calibrators,human PCT (amino acids 1–115)was overexpressed in Escherichia coli and purified by anion-exchange and reversed-phase chromatography as described previously (14).For the highest calibrator (S6),5000ng/L human recombinant PCT was added to horse serum (Sigma).This was calibrated by use of the LUMItest PCT and diluted to prepare calibrators S2to S5with final concentrations of 20,100,500,2000,and 5000ng/L.The lowest calibrator,S1(PCT-free horse serum),was defined as 5ng/L PCT to allow logarithmic plotting of the calibration curve.As controls,horse sera containing 50ng/L (control I)and 1000ng/L (control II)were added at the beginning and end of each run.The intraassay imprecision was determined by measur-ing 23human serum samples covering the range of the calibration curve in 10parallel determinations.The in-traassay CV was Ͻ8%in samples containing 8–4000ng/L PCT and Ͻ15%in samples containing Ͻ8ng/L PCT.The interassay imprecision was determined by measuring the same samples on 10different days (Fig.1A).The func-tional assay sensitivity (interassay CV Ͻ20%)was Ͻ7ng/L PCT.To compare this new assay with the established LUMI-test PCT,we measured 71serum samples from patients with sepsis who had PCT values between 250and 5000ng/L in both assays.The mean difference (SD)was 11.6(256.4)ng/L (15)(Fig.1B).In 500healthy individuals,the range was Ͻ7to 63ng/L PCT.The median was 13.5ng/L (95%confidence interval for the mean,12.6–14.7ng/L).The 97.5percentile of the population studied was 42.5ng/L (Fig.1C).There were no significant differences in the range and median PCT values between males and females or among age groups.Similar low concentrations were reported by Snider et al.(8),who used HPLC-extracted calcitonin precursors from pooled serum of healthy males.We conclude that the proposed assay can measure PCT in healthy individuals or patients without systemic in-flammatory response syndrome/sepsis.PCT values in healthy individuals are more than 10-fold lower than the clinical cutoff used for the diagnosis of severe systemic bacterial infection or sepsis (500ng/L).At present,PCT can not be used for the diagnosis or monitoring of local bacterial infections because the established ILMA does not detect PCT concentrations Ͻ300ng/L.The proposed assay may be useful to evaluate whether local bacterial infections increase PCT above the reference intervals.We thank Tao Chen,Uwe Zingler,and Elke Seidel-Mu ¨ller for excellent technical assistance.We also acknowledge Dr.Barbara Thomas for helpful discussions.References1.Rau B,Steinbach G,Gansauge F,Mayer JM,Grunert A,Beger HG.The potential role of procalcitonin and interleukin 8in the prediction of infected necrosis in acute pancreatitis .Gut 1997;41:832–40.2.Brunkhorst FM,Eberhard OK,Brunkhorst R.Early identification ofbiliaryFig.1.Characteristics of the ProCa-S assay for PCT.(A ),interassay CVs for the same samples on 10different days.(B ),Bland –Altman plot comparing difference between the results obtained with the LUMItest and ProCa-S assays as a function of the mean values obtained with both assays (15).(C ),frequency distribution of PCT values in 500healthy controls.Clinical Chemistry 48,No.5,2002789pancreatitis with procalcitonin[Letter].Am J Gastroenterol1998;93: 1191–2.3.Nylen ES,O’Neill W,Jordan MH,Snider RH,Moore CF,Lewis M,et al.Serumprocalcitonin as an index of inhalation injury in burns.Horm Metab Res 1992;24:439–43.4.Mimoz O,Benoist JF,Edouard AR,Assicot M,Bohuon C,Samii K.Procalci-tonin and C-reactive protein during the early posttraumatic systemic inflam-matory response syndrome.Intensive Care Med1998;24:185–8.5.Assicot M,Gendrel D,Carsin H,Raymond J,Guilbaud J,Bohuon C.Highserum procalcitonin concentrations in patients with sepsis and infection.Lancet1993;341:515–8.6.Dandona P,Nix D,Wilson MF,Aljada A,Love J,Assicot M,et al.Procalcitoninincrease after endotoxin injection in normal subjects.J Clin Endocrinol Metab1994;79:1605–8.7.Gendrel D,Assicot M,Raymond J,Moulin F,Francoual C,Badoual J,et al.Procalcitonin as a marker for the early diagnosis of neonatal infection.J Pediatr1996;128:570–3.8.Snider RH Jr,Nylen ES,Becker KL.Procalcitonin and its component peptidesin systemic inflammation:immunochemical characterization.J Invest Med 1997;45:552–60.9.Whang KT,Steinwald PM,White JC,Nylen ES,Snider RH,Simon GL,et al.Serum calcitonin precursors in sepsis and systemic inflammation.J Clin Endocrinol Metab1998;83:3296–301.10.Muller B,Becker KL,Schachinger H,Rickenbacher PR,Huber PR,ZimmerliW,et al.Calcitonin precursors are reliable markers of sepsis in a medical intensive care unit.Crit Care Med2000;28:977–83.11.Nylen ES,Whang KT,Snider RH Jr,Steinwald PM,White JC,Becker KL.Mortality is increased by procalcitonin and decreased by an antiserum reactive to procalcitonin in experimental sepsis.Crit Care Med1998;26: 1001–6.12.Muller B,White JC,Nylen ES,Snider RH,Becker KL,Habener JF.Ubiquitousexpression of the calcitonin-I gene in multiple tissues in response to sepsis.J Clin Endocrinol Metab2001;86:396–404.13.Domenech VS,Nylen ES,White JC,Snider RH,Becker KL,Landmann R,etal.Calcitonin gene-related peptide expression in sepsis:postulation of microbial infection-specific response elements within the calcitonin I gene promoter.J Invest Med2001;49:514–21.14.Wrenger S,Kahne T,Bohuon C,Weglohner W,Ansorge S,Reinhold D.Amino-terminal truncation of procalcitonin,a marker for systemic bacterial infections,by dipeptidyl peptidase IV(DP IV).FEBS Lett2000;466:155–9.15.Bland JM,Altman DG.Statistical methods for assessing agreement be-tween two methods of clinical ncet1986;1:307–10. Comparison of Cardiac Troponin I in Serum and Hep-arin Plasma with the Dimension RxL Assay,Alberto Cerutti,*Leonora Corsini,Roberto Finotto,and Carlo Perazzi (Clinical Laboratory,S.Biagio Hospital,28845Domodos-sola,Italy;*author for correspondence:fax39-0324-4961247,e-mail labanalisidomo@asl14.it.)Cardiac troponin[I(cTnI)and T(cTnT)]assays in blood have rapidly become alternatives to older methods for detecting myocardial damage(1,2).Furthermore,the re-cently redefined criteria for myocardial infarction that are used to classify patients with acute coronary syndrome have been established on the basis of increased serum/plasma cTnI or cTnT(3).The National Academy of Clinical Bio-chemistry has recommended the use of plasma rather than serum as the specimen of choice(4),citing improved turn-around times and potentially avoiding incomplete serum separation that may influence some methods to produce falsely increased results(5).However,some studies have shown lower cTnI and cTnT concentrations in plasma than in serum(6,7).Because heparin effects vary among different analytical methods,we performed a study to evaluate cTnI concentrations in plasma and serum specimens assayed on the Dimension RxL(Dade Behring).We evaluated assay imprecision using lyophilized controlsera with three different concentrations of cTnI(0.57,5,and15␮g/L)that were analyzed10times in one analytical run for the determination of within-run imprecision and24times on24different days for the determination of between-run imprecision.Our results confirmed the manufacturer’sclaims that within-and between-run imprecisions(CVs)were2.8–3.9%and2.9–4.1%,respectively.The analyticalsensitivity was0.04␮g/L,defined as the concentration corresponding to a signal that was2SD above the signaldetected for the0␮g/L cTnI calibrator(nϭ20).To compare plasma and serum cTnI,100paired ran-domized blood samples were obtained from patients admitted to the Division of Cardiology(nϭ64)or to the Emergency Room(nϭ36)of our hospital for acute myocardial infarction(AMI)or suspected AMI.The paired samples were drawn in parallel into tubes without anticoagulant(cat.no.367615;Becton Dickinson)and into tubes with lithium heparin(ϳ65IU of heparin/mL plasma considering an hematocrit of50%;cat.no.367684; Becton Dickinson).According to the consensus document of the European and American Cardiologists(3),blood was obtained from our patients on hospital admission,at 6to9h and again at12to24h if the earlier samples were negative and the clinical index of suspicion was high.We used a cTnI cutoff for AMI at0.6␮g/L as indicated by the manufacturer.The Dimension RxL assay,like all the other troponin assays(8),does not comply with the new consensus requirement(3)of aՅ10%CV at the99th percentile(0.07␮g/L)of a reference group.Within10–15 min after venipuncture,both tubes were centrifuged at 3000g for10min,and the serum and heparin-plasma samples were frozen atϪ20°C until cTnI determination. Before assay,the specimens were thawed,gently mixed by inverting the tubes five to eight times,and recentri-fuged at3000g for10min.The cTnI concentration ranges for serum and plasmawere0.24–48.5␮g/L and0.28–48.2␮g/L,respectively, well above the detection limit of the assay(0.04␮g/L as indicated above).No significant difference was foundbetween serum and plasma cTnI concentrations(101.7Ϯ2.4%;t-test for paired data,Pϭ0.90),with an excellentcorrelation(rϭ0.993;PϽ0.001;cTnI plasmaϭ1.00ϫcTnI serumϪ0.02).Whereas the ratio between plasma and serum cTnI concentrations was rather wide(range,53.8–125%),no significant correlation was found between thisratio and the mean plasma-serum cTnI concentration(Pϭ0.63).Interestingly,only one sample showed a high un-derestimate in plasma cTnI concentration compared withserum(ϳ46%).This sample gave the same result whenrepeatedly analyzed(three times)to exclude sporadicerror attributable to a small clot,bubble,or misidentifica-tion.For the other99samples,the plasma/serum cTnIratio was between0.76and1.25(Fig.1).To clarify this problem,we also carried out heparintitration experiments by adding increasing volumes ofheparin(5000IU/mL)to serum aliquots of10samples(with cTnI between0.24and20.2␮g/L)to final concen-790Technical Briefs。

CDC funds 33 areas to conduct incidence surveillance. These areas were to use one of three protocols in light of regulatory requirements regarding informed consent as applied to the STARHS testing (detuned assay).
FDA designates the BED assay as a surveillance, not a diagnostic, test. This designation sets the stage for population-based incidence surveillance. Additional level of consent to employ STARHS testing is no longer needed and all areas could implement one protocol.
HIV Incidence Methodology Timeline
1998
2001 (Feb)
2001 (Fall) 2001 (Oct)
2001 (Oct) 2002 (Dec) 2004 (Jan)
2005 (Mar)
2005
CDC publishes a description of the STARHS assay, a laboratory test that can distinguish recent HIV infections from long-standing ones on a population basis. (Janssen RS, Satten GA, Stramer SL, et al. New testing strategy to detect early HIV-1 infection for use in incidence estimates and for clinical and prevention purposes. JAMA 1998; 280:42-48.)

2022年考研考博-考博英语-全国医学统考考试预测题精选专练VII（附带答案）第1套一.综合题(共25题)1.单选题问题1选项A.The woman arrived ahead of schedule.B.The woman failed to meet her tennis appointment.C.The man did not play the tennis game by the rule.D.The man helped put the woman on the waiting list.【答案】B【解析】7. W: I reserved a tennis court. It’s taken over by someone else.M: Yes, mom. I understand. We have a policy that every party is more than 15 minutes late for a starting time. We scheduled the courts for other waiting guests.【试题解析】推理判断题。

题干为：从这段交谈中可以得出什么？由文中“We have a policy that every party is more than 15 minutes late for a starting time.（我们有规定，每场顶多迟到15分钟）”，推测可知B选项“The woman failed to meet her tennis appointment.（女士错过了网球场预约时间）”符合原文。

A选项“女士提早到了”；C选项“这个男人没有按规则打网球”；D选项“这个男人帮女士把她放在等候名单上”不符合原文。

2.单选题There are ill effects on the health of older people when their activities are restricted;（）, intervention that increases the range of their activities promotes their health.问题1选项A.in additionB.in contrastC.in turnD.in short【答案】B【解析】【选项释义】A. in addition 此外B. in contrast 与此相反C. in turn 依次；轮流；反过来D. in short 总之；简而言之【答案】B【考查点】词组辨析。

Inflammation, Tissue Damage and RepairWhen living tissues are injured, a series of changes, which may last for hours, days, or weeks, occurs in and around the area of injury. This response to injury is known as inflammation.The injury is abnormal but the body’s reaction, inflammation, is a normal, if complex, physiological reaction ----the only one possible in the circumstances of that particular injury. This reactive nature of inflammation was first recognized by John Hunter (1794), who, after his studies of war wounds, concluded: “Inflammation is itself not to be considered as a disease, but as a salutary operation consequent either to some violence or some disease”. The purpose of inflammation is to localize and eliminate the causative agent, limit tissue injury, and restore tissue to normality.The inflammatory response is usually beneficial, indeed it is essential in combating most infections and in limiting the harmful effects of many toxic agents. However it is not always of benefit. There are many situations when destruction of tissue or other untoward effects are due not to the damaging agent but to one or other aspect of the body’s response to injury. For example in acute inflammation of the larynx, there may be sufficient inflammatory swelling to obstruct the airway and cause death from asphyxia. Inflammation is best considered not as a single process but as a collection of distinct processes, each of which may have evolved for defence against injury, but each of which has also potentially deleterious effects.Inflammation can be divided into two types: acute and chronic. The division of inflammation is based according to the time course and cellular components involved. These categories are not mutually exclusive, and some overlap exists.Acute inflammation is the immediate and early response to an injurious agent and affects the vascular and connective tissue adjacent to the injured cells. There are three major components in the process of acute inflammation: increased blood flow (vasodilation), increased vascular permeability (exudation) and egress of white blood cells into the injured tissue (emigration). These three components are coordinated and interrelated by numerous chemical mediators produced or released at the site of injury.Vasodilatation. Vasodilatation occurs directly after injury. Normally blood flow to the capillary bed is limited by the precapillary sphincter. In acute inflammation, a phase of vasodilatation occurs when the arterioles and precapillary sphincters relax. This results increased blood flow to the injured area and increased hydrostatic pressure. But blood soon flow slowly, because a concomitant increase in vascular permeability and loss of plasma water raises the viscosity of the blood. In the slowly moving blood, the pattern of flow changes. Red cells tend to clump in the centre of the vessel lumen and leucocytes assume a more peripheral position near the vessel wall. This margination of leucocytes is an important initial step in the emigration process. If flow becomes very slow, the blood may clot and form a thrombus.Exudation. This is the increased passage of fluid and solutes, notably proteins, through the vessel wall. The mechanisms leading to increased vascular permeability are complex and incompletely understood. They include endothelial cell contraction or damage, the effects of mediators, local haemodynamic forces and the osmotic effects of proteins escaping into interstitial tissue. The leak of protein is roughly in proportion to their molecular size. Albumin is in the greastest amount, but if vascular permeability is extensive, large amounts fibrinogen may leak out. Exudation is an important local defence mechanism. The increase in interstitial fluid dilutes toxins, and proteins such as globulins are effective in neutralizing agents like bacteria. This increased fluid is sometimes called inflammatory oedema or simply oedema.Emigration. Emigration of white blood cells, principally neutrophils and monocytes, is also an important defence mechanism. These are phagocytic cells which engulf and digest foreign particulate matter such as bacteria and debris of dead cells. The emigration of leucocytes is an active process which occurs in two stages. The cells stick to the endothelial surface and then actively migrate through the gaps between the endothelial cellsand into the tissue spaces.Acute inflammation is the first step in a dynamic response to injury. The sequelae depend on the nature and extent of injury. Resolution means the complete restoration of normal condition after the cause of the acute inflammation is removed. This occurs when there is minimal cell death and tissue damage, rapid elimination of the causal agent, and local condition favouring the removal of fluid and debris by lymphatics and by phagocytosis.Some types of inflammatory reaction are of much longer duration than those so far described, persisting for weeks or months after the initial injury. Any prolonged inflammation in termed chronic, the term referring solely to the duration of the inflammatory process.There are two main types of chronic inflammation: chronic supervening on acute and chronic developing slowly with no initial acute phase.Chronic inflammation supervening on acute is almost always suppurative in type and presents as a persistent discharge of pus from an abscess which has ruptured or been drained surgically. Suppurative inflammation is usually caused by infection with pyogenic bacteria such as staphylococcus aureus and streptococcus pyogenes. There are two types of suppurative inflammation: superficial, e.g. a boil, and deep-seated, e.g. an abscess within a hollow viscus such the gall bladder.Chronic developing slowly with no initial acute phase. This type of response occurs after many types of injury. The injury may be physical, chemical, such as the response to talc or asbestos, or may result from poor local circulation. Certain micro-organisms, including those that cause tuberculosis and syphilis, characteristically induce chronic inflammation. In still other types of chronic inflammation, including rheumatoid arthritis and ulcerative colitis, the cause is not known but disturbances of immune mechanisms are believed to play an important aetiological role.炎症，组织损伤和修复当活组织受损时，损伤区及其周围会发生一系列的变化，这些变化可持续数小时、数天或数周。