Prezados Clientes,
Dando continuidade ao nosso informativo BN-NEWS,
anexamos o de numero 16 – Setembro de 2005 - onde
destacamos a V.S. o intenso menu de testes que dispõe o
sistema de nefelometria (BN-II/BNPS e BN 100) com
Nesta Edição
Menu Extenso
de Provas
calibradores, controles, diluente e tampão múltiplos, aonde
deixa sua prova por teste muito mais barato. Destacamos
nesta lista de produtos, os testes de Ferritina, IgE, Beta 2
microglobulina, SubClasses de IgG1-4, PCR ultrasensível,
Versatilidade em
Equipamentos
Soro Amilóide A (SAA)
e Proteína C Reativa
(PCR) e seus valores
diagnósticos nas Reações de Fase Aguda
Cistatina C, sTfR (Receptor Soluvel de Transferrina), , kappa
e lambda no soro e na urina, Ceruloplasmina, Haptoglobina,
Hemopexina, RPB, PreAlbumina, SAA, â Trace Proteinas e
HOMOCISTEÍNA como futuro lançamento, etc...
Anexamos também artigos cientificos sobre: Cistatina C ,
Beta Trace Proteínas e Microalbuminúria como marcador
cardíaco.
Aproveitamos para sugerir a oportunidade de
também enviar esses informativos á alguns médicos que
Comparison of B2 Transferrin and B - Trace
Protein for Detection of
Cerebrospinal Fluid in
Nasal and Ear Fluids
Cystatin-C and Mortality
in Elderly Persons With
Heart Failure
trabalham com V.S. para um melhor conhecimento da linha
de Plasma Proteínas com todas as novidades no mercado
mundial e também de saberem que o Laboratório de apoio
que utilizam já estão capacitados a realizar tais testes.
Atenciosamente
CLAUCUS MERCATELLI
Gerente de Produto
Extenso Menu
2
Código
OSAS
OSAR
OSAT
OQGA
OQGB
OQGC
OQGD
OSAP
OSAO
OSAL
OSAX
OSAV
OUVN
OUIE
OSAW
OSAZ
OWLA
OSAM
OSAY
OSCA
OSCB
OUND
OWHG
OWHH
OUIF
OUVO
OUED
OSAN
OQBA
OQDL
OQHL
OUUA
OQIY
OUSS
OWIA
OUWW
OQTH
OQNM
OQMP
OQTC
OWTI
OQTG
NCMH
PRODUTO
IgG–Soro/Urina/CSF
IgA-Soro/Urina/CSF
IgM-Soro/Urina/CSF
IgG 1
IgG 2
IgG 3
IgG 4
C3c
C4
Albumina-Urina/soro
Transferrina-Soro/Urina
Haptoglobina
Hemopexina
Ceruloplasmina
Alfa1Glicop.Ácida
Alfa1Antitripsina
Alfa1microglobulina
Alfa2macroglobulina
Antitrombina III
Fibrinogênio
Plasminogênio
Fibronectina
Kappa – Soro/Urina
Lambda Soro/Urina
Prealbumina
RBP
Apolipoproteína A1
Apolipoproteína B
Apolipoproteína AII
Apolipoproteina E
Lp(a)
Fator Rematóide - RF
PCR / PCR ultrasensível
ASL
Mioglobina
Beta2Microgl.Soro/urina
Ferritina
Cistatina C
Soro Amilóide A - SAA
STF-Receptor de Transf.
ADNase B
N Látex IgE
CIC
TESTES
125/50
125/50
125/50
37
37
37
37
125/50
125/50
125/50
125/50
125/50
125/50
125/50
166/66
125/50
125/50
125/50
125/50
125/50
125/50
40
166/66
50
125/50
125/50
125/50
125/50
50
50
105
300
150
300
75
105
210
90
105
90
105
135
100
teste
CAUSAS
Imunidade, mieloma, leucemia, lúpus
Imunidade, mieloma, cirrose, infecções
Imunidade, mieloma, hepatite, infecções
Imunodeficiência, sindrome nefrótica
Infecções respiratórias, nefrose,
Infecções respiratórias, asma
Dermatite, asma, doenças parasitárias
Lupus, imunidade, infecções, inflamações
Lupus imunidade, deficiência congênita
Desnutrição, infecções, cirroses, desidratação
Anemias, tumores, inflamações, infecções
Inflamações, tuberculose, doenças hepáticas
Artrites, mielomas, hemólise, inflamações
Tumores, infartos, hepatite, inflamações
Mielomas, inflamações, infecções
Tumores malignos, infecções, inflamações
Diabetes, insuficiencia renal, proteinúria
Doenças hepáticas, cardíacas, diabetes
Trombose, embolismo pulmonar
Mieloma, nefrose, cirrose, gravidez, infarto
Hiperfibrinólise, coagulação vascular
Marcador tumoral
Mielomas
Mielomas
Proteinúrias, desnutrições, inflamações
Ulceras, desnutrições, doenças hepáticas
Arteriosclerose, infarto –HDL
Infarto, arteriosclerose, angina, nefrose-LDL
Arteriosclerose, infarto
Degradação aterogenica dos quilomicrons
Arteriosclerose, aneurisma
Rematismo, artrites
Reumatismo, Infarto, infecções
Reumatismo, artrites, infecç
Infarto agudo do miocárdio
AIDS, leucemia, mieloma, imunidade, hepatite
Anemia, artrite, cirrose, mieloma, ictericia
Substituto da Clearence de creatinina
Infarto, marcador de inflamação
Anemias, marcador de eritropoetina
Estreptococos
Alergias, doenças parasitárias, etc
Complexo Imune Circulante
Dispomos também de calibradores, controles e tampões multiplos:
CÓDIGO
OQIM
PRODUTO
N Protein Standard SL
OUDI
N Protein Standard PY
OUPG
OQKZ
OQLV
N Apolip.Standard
N Rheumat. Std SL
N Protein Standard UY
TESTES
IgG,A,M,E SubClasses,C3C4,Alfa1Glic. Ácida,
kappa,Lambda,Ferritina,RPB,
Prealbumina,Ceruloplasmina, STF,
B2microglob.,Alfa1Antripsina,Albumina,
Alfa2macroglobulina
ATIII,Fibrinogênio, Fibronectina,
Plasminogênio e C1-inibidor.
ApoAI,AII,B e E
PCR, ASL e RF
Cystatina C e Alfa1Microglobulina
Extenso Menu
PADRÕES
CONTROLES
CÓDIGO
PRODUTO
TESTES
OQIO
OQIN
OQIP
N/T Protein Control SL/M,L,H
OWSY
N/T Protein Control PY
OUPH
OQDB
OQDC
OQLW
Control Apo
N/T Rheuma Control SL/1 e2
IgG,A,M,E SubClasses,C3C4,Alfa1Glic. Ácida,
kappa,Lambda,Ferritina,RPB,
Prealbumina,Ceruloplasmina, STF,
B2microglob.,Alfa1Antripsina,Albumina,
Alfa2macroglobulina
ATIII,Fibrinogênio, Fibronectina, Plasminogênio
e C1-inibidor.
ApoAI,AII,B e E
PCR, ASL e RF
N/T Protein Control LC
Valores para todas as provas com CSF e Urina.
CONSUMÍVEIS
CÓDIGO
PRODUTO
OUMT
N Diluent
OUMS
N Buffer
OQTD
N Sup.Reag. L
OUMU
N Reagente Suplementar
TESTES
IgE e sTfR
PreAlbumina, PCR, PCR ultrasensível, SAA,
Apolipoproteinas A1 e B, Fibrinogenio, ATIII,
Plasminogenio e Sub Classes de IgG2 e 4
teste
3
Versatilidade em equipamentos
Plasma Proteínas
Sistemas para análises de proteínas plasmáticas, com uma grande variedade de ensaios para auxílio
diagnóstico e monitoramento de riscos cardiovasculares; doenças inflamatórias agudas e crônicas; doenças
reumáticas; estado imune; estado nutricional; função renal e metabolismo de ferro.
BN II
Automação completa
O Nefelômetro BN II executa
automaticamente todos os passos dos
ensaios de proteínas plasmáticas desde a
leitura das etiquetas de códigos de barras
até a validação dos resultados.
O alto grau de automação, aliado à grande
capacidade de entrada de amostras e
reagentes no analisador (100 amostras
com acesso contínuo e 35 reagentes a
bordo) transformam o BN II no sistema
ideal para grandes rotinas, com capacidade
de até 225 amostras por hora.
BN ProSpec
O Nefelômetro BN ProSpec é um
analisador de proteínas plasmáticas,
flexível, com as seguintes
características:
Verifica excesso de antígeno;
Código de barras em todos os
líquidos;
SubClasses de IgG e imunoglobulinsas no idoso
Detecção de nível, amostras,
Acesso randômico;
Capacidade de 80 amostras por hora;
Operação de 24 horas;
Estação de refrigeração de reagentes.
reagentes padrões e controles;
Módulo de pré-reação, com acesso
4
contínuo de amostras, controles,
Capacidade de realizar urgências
padrões e reagentes;
(STAT);
teste
Plasma Proteínas
Testes
especiais de
Nefelometria
Cardiophase hsCRP - PCR ultrassenssível - Marcador cardíaco
Cistatina C - Filtração Glomerular (substituto da Clearence de
Creatinina) e agora também como marcador cardíaco
beta Trace Proteínas - Detecção de Meningite bacterianas, Lesão osséa
(Principalmente crânio) Problemas internos de ouvidos, Corrimento
Nasal - Sinusite
Inativador C1 - inibidor de esterase C1 - Leucemia linfática crônica,
mieloma múltiplo, linfomas malignos, inchaço dos tecidos.
ADNase B - Febre reumática, escarlatina, glomerulonefrite, etc..
Complexo Imune Circulante - CIC - Níveis elevados de CIC podem ser
encontrados em artrite reumatóide e doenças parasitárias.
sTfR - Deficiência de Ferro e monitorização de eritropoetina
IgE - Alergias, rinite, asma, doenças parasitárias
SubClasses de IgG1-4 - Asma, Infecções respiratórias, dermatite,
imunidade, etc.
Menu de Testes
Marcadores cardíacos
ApoA1, ApoB, Lp(a), Cardiophase hsCRP, Mioglobina, Fibrinogênio
Infecções cronicas, doenças autoimunes, deficiências imunológicas,
tumores, neurologias
IgA, IgG, IgM, SubClasses de IgG 1-4, kappa e lambda.
Lançamentos
previstos
para 2005
Doenças Reumáticas
ASL, PCR, FR, C3, C4 e ADNaseB
Inflamação
Alfa 1 Glicop.Ácida, Alfa1-Antitripsina, Ceruloplasmina, Haptoglobina,
Cardiophase hsCRP
Malnutrição
Prealbumina, Albumina, RBP, Transferrina, Ferritina, PCR
Nefropatias (renal)
N Látex Homocisteína*
para BN II e BNPS marcador cardíaco
Alfa1-Microglobulina, Alfa2-Macroglobulina, Beta2-Microglobulina,
Cistatina C, Albumina, Transferrina.
Atividade do Complemento
C3c e C4
Alergia
IgE
N Látex CDT*
Carbohidrato Deficiente de
Transferrina C - marcador
específico para o diagnóstico
e monitorização para
alcoolismo crônico
Anemias
Haptoglobina, Ferritina, sTfR, Transferrina
Coagulação
Antitrombina III, Fibrinogenio, Plasminogênio, C1
Meningite
Beta Trace Proteínas
*- Em fase de registro
5
Clinical Chemistry 50, No. 3, 2004
4. Matsushita M, Hijikata M, Ohta Y, Iwata K, Matsumoto M, Nakao K, et al.
Hepatitis C virus infection and mutation of mannose-binding lectin gene
MBL. Arch Virol 1998;143:645–51.
5. Zhao H, De BP, Das T, Banerjee AK. Inhibition of human parainfluenza
virus-3 replication by interferon and human MxA. Virology 1996;220:330 – 8.
6. Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K,
et al. A second series protease associated with mannan-binding lectin that
activates complement. Nature 1997;386:506 –10.
7. Ozsoz M, Erdem A, Kerman K, Ozkan D, Tugrul B, Topcuoglu N, et al.
Electrochemical genosensor based on colloidal gold nanoparticles for the
detection of factor V Leiden mutation using disposable pencil graphite
electrodes. Anal Chem 2003;75:2181–7.
8. Authier L, Grossiord C, Brossier P. Gold nanoparticle-based quantitative
electrochemical detection of amplified human cytomegalovirus DNA using
disposable microband electrodes. Anal Chem 2001;73:4450 – 6.
9. Patolsky F, Lichtenstein A, Willner I. Detection of single-base DNA mutations
by enzyme-amplified electronic transduction. Nat Biotechnol 2001;19:253–7.
10. Boon EM, Ceres DM, Drummond TG, Hill MG, Barton JK. Mutation detection
by electrocatalysis at DNA-modified electrodes. Nat Biotechnol 2000;18:
1096 –100.
11. Cha J, Han JI, Choi Y, Yoon DS, Oh KW, Lim G. DNA hybridization
electrochemical sensor using conducting polymer. Biosens Bioelectron
2003;18:1241–7.
12. Vagin MY, Karyakina EE, Hianik T, Karyakin AA. Electrochemical transducers
based on surfactant bilayers for the direct detection of affinity interactions.
Biosens Bioelectron 2003;18:1031–7.
13. Fan C, Plaxco KW, Heeger AJ. Electrochemical interrogation of conformational changes as a reagentless method for the sequence-specific detection
of DNA. Proc Natl Acad Sci U S A 2003;100:9134 –7.
14. Umek RM, Lin SW, Vielmetter J, Terbrueggen RH, Irvine B, Yu CJ, et al.
Electronic detection of nucleic acids: a versatile platform for molecular
diagnostics. J Mol Diagn 2001;3:74 – 84.
15. Hashimoto K, Ito K, Ishimori Y. Novel DNA sensor for electrochemical gene
detection. Anal Chim Acta 1994;286:219 –24.
16. Hashimoto K, Ito K, Ishimori Y. Sequence-specific gene detection with a gold
electrode modified with DNA probes and an electrochemically active dye.
Anal Chem 1994;66:3830 –3.
17. Hashimoto K, Ito K, Ishimori Y. Microfabricated disposable DNA sensor for
detection of hepatitis B virus DNA. Sens Actuators B Chem 1998;46:220 –5.
18. Hashimoto K, Ishimori Y. Preliminary evaluation of electrochemical PNA
array for detection of single base mismatch mutations. Lab on a Chip
2001;1:61–3.
19. Watanabe H, Enomoto N, Nagayama K, Izumi N, Marumo F, Sato C, et al.
Number and position of mutations in the interferon (IFN) sensitivity-determining region of the gene for nonstructural protein 5A correlate with IFN
efficacy in Hepatitis C virus genotype 1b infection. J Infect Dis
2001;183:1195–203.
DOI: 10.1373/clinchem.2003.023283
Comparison of ␤2-Transferrin and ␤-Trace Protein for
Detection of Cerebrospinal Fluid in Nasal and Ear
Fluids, Claudia Schnabel,1* Ercole Di Martino,2 Joachim M.
Gilsbach,3 Dieter Riediger,4 Axel M. Gressner,1 and Dagmar
Kunz1† (1 Institute of Clinical Chemistry and Pathobiochemistry, 2 Otorhinolaryngology and Plastic Head
and Neck Surgery, 3 Clinic of Neurosurgery, and 4 Oral
and Maxillofacial Surgery, University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany; * address correspondence to this author at: Institut für Klinische Chemie/
Zentrallaboratorien, Universitätsklinik Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany; fax 49-40428039037, e-mail [email protected]; † current address: DRK-Hospital Neuwied, Department for
Laboratory Medicine, Marktstrasse 104, 56567 Neuwied,
Germany)
Cerebrospinal fluid (CSF) fistulas occur mainly in basal
skull fractures or operations at the skull base entailing a
661
dural defect; up to 40% of CSF fistulas are spontaneous
(1 ). The treatment consists of surgical closure of the dural
defect. Complications such as intracranial abscess or bacterial meningitis may develop, with a mortality rate of
25–50%. Therefore, a simple and reliable diagnosis of CSF
fistulas is of great importance.
␤-Trace protein is synthesized mainly in the epithelial
cells of the choroid plexus and is found in CSF in
concentrations ⬃35-fold higher than in plasma (2 ). Thus,
␤-trace protein represents a potentially useful marker for
the diagnosis of CSF leakage (3 ), with immunoelectrophoresis having a specificity of 100% and a sensitivity of
91% for the diagnosis of CSF leakage (4 ).
␤2-Transferrin, the asialo form of transferrin, is produced by neuraminidase activity in the brain and is
usually detectable only in CSF, perilymph, and aqueous
humor. Thus, like ␤-trace protein, it is a potentially useful
marker to diagnose CSF leakage (3 ).
In the present work we compared the first two commercially available assay systems: a new, sensitive immunofixation method from Sebia GmbH for detection of
␤2-transferrin and an automatic, quantitative immunonephelometric assay from Dade Behring for detection of
␤-trace protein. We also established a cutoff value for
␤-trace protein and evaluated the potential of both markers as indicators of CSF leakage.
The ␤-trace protein assay is based on latex particle
enhancement using rabbit polyclonal antibodies against
␤-trace protein. Calibrators contain ␤-trace protein purified from CSF (N Protein Standard UY®; Dade Behring).
Imprecision was assessed by assaying N/T protein Control LC® (Dade Behring). Measurements were performed
on a BN II analyzer (Dade Behring). The assay covers a
range of 0.25–15.8 mg/L in the initial 1:100 dilution. The
within-day imprecision (CV) was 12% at 0.68 mg/L (n ⫽
10) in serum and 2.8% at 18.3 mg/L (n ⫽ 10) in CSF.
Between-day CV were 15% at 0.74 mg/L (n ⫽ 10) in
serum and 10% at 19.4 mg/L (n ⫽ 10) in CSF. At least 200
␮L (35-␮L sample volume) is required for a single measurement, which requires 20 min.
␤2-Transferrin was detected with the Hydrasys LC
(Sebia GmbH) electrophoretic system, which separates the
more cathodic asialo form of transferrin from an anodic
fraction containing the sialo forms. Both transferrin fractions are detected by immunofixation with anti-transferrin antibodies labeled with peroxidase. A patient’s
serum sample is investigated in parallel in a 1:100 dilution
to avoid false-positive results in case of alcoholism. The
assay required 10 ␮L and 120 –150 min.
For comparison of the detection limits for ␤2-transferrin
(Sebia GmbH Hydrasys LC) and ␤-trace protein (Dade
Behring BN II), both proteins were analyzed in samples
generated by dilution of a CSF pool (containing 16.3
mg/L ␤-trace protein). We measured ␤-trace protein and
␤2-transferrin in nasal fluids from 7 healthy volunteers
and ␤-trace protein in nasal and ear fluids from 26
patients (17 males and 9 females; age range, 5–74 years)
and ␤2-transferrin in samples from 25 patients. All were
admitted to the Otorhinolaryngology, Neurosurgery, or
662
Technical Briefs
Oral and Maxillofacial Surgery departments at our Hospital between July 2000 and August 2003. Laboratory
investigations were performed without information about
the clinical diagnosis.
Rhinoliquorrhea was suspected in 22 patients, otoliquorrhea in 2 patients, and subcutaneous and transcutaneous fistulas in 2 patients (Table 1 in the Data Supplement that accompanies the online version of this
Technical Brief at http://www.clinchem.org/content/
vol50/issue3/). Laboratory investigations were performed as a precaution or because the patients presented
with suspicious clinical symptoms or on computed tomography scans after surgical intervention, accidents, or
spontaneously. Evidence for a CSF fistula was obtained in
13 patients (9 males and 4 females) by typical clinical
symptoms, computed tomography, cysternography, or
intraoperative findings (Table 1 in the online Data Supplement). The CSF and serum samples were collected for
diagnostic workup.
Nose and ear fluid was collected in the gauze of
Salivettes (Sarstedt). The secretions were separated from
the Salivette gauze by centrifugation at 2000g for 10 min
and stored at 4 °C at most for 1 day. Serum was collected
into serum separator tubes (Sarstedt) and centrifuged at
2000g for 10 min immediately after arriving in our laboratory. CSF was centrifuged for 10 min at 2000g.
Statistical analysis was performed with SigmaPlot 2001
for Windows.
Parallel measurements of ␤-trace protein and ␤2-transferrin in samples from a CSF pool (16.3 mg/L ␤-trace
protein) diluted down to 0.1 mg/L ␤-trace protein (1:128
dilution) revealed linear quantification of ␤-trace protein
(r2 ⫽ 0.999; y-intercept, 0.0286 mg/L), whereas the detection limit for ␤2-transferrin was at the 1:32 dilution.
In nasal fluids from the seven volunteers, ␤-trace protein concentrations were ⬍0.25 mg/L, and ␤2-transferrin
was detected in none. In patients without CSF fistula,
␤-trace protein concentrations were ⬍0.25– 0.95 mg/L. In
one patient with nasal secretion during provocation test-
A
Fig. 1. Electrophoretic detection of ␤2-transferrin in
a CSF pool (A), and representative results of electrophoretic detection of ␤2-transferrin in nasal fluid/serum pairs from four patients suspected for
rhinoliquorrhea and CSF as positive control (B).
(A), the pool was variably diluted with saline from 1:1.5 to
1:128. (B), the numbering corresponds to that of Table 1
in the online Data Supplement. N, nasal fluid; S, serum.
B
ing (bowing during abdominal press), a typical symptom
for rhinoliquorrhea, no ␤2-transferrin was detected and
␤-trace protein tested 3 months later was ⬍0.25 mg/L
(patient 13 in Table 1 in the online Data Supplement).
These results might be attributable to collection of nasal
fluid without actual CSF leakage in an intermittent rhinoliquorrhea.
In 12 patients with confirmed CSF fistulas, ␤-trace
protein concentrations were 2.5–35 mg/L. At a cutoff of 1
mg/L, the sensitivity was 100% (statistical uncertainty,
78 –100%; P ⬎0.05), and the specificity was 100% (86 –
100%; P ⬎0.05) for the diagnosis of CSF leakage.
␤2-Transferrin was detected in 8 of 11 patients (73%)
with CSF leakage. In 37% of all investigated patients
(three patients with and six without CSF fistulas), no
interpretation of the immunofixation was possible because of an overlap of the transferrin band with the
␤2-transferrin band. The detailed data are presented in
Table 1 in the online Data Supplement and in Fig. 1B.
Diagnosing CSF fistulas is always challenging. Particularly in subclinical liquorrhea with a loss of small quantities of CSF, the fistula may not detectable by radiologic
imaging. Because of the risk of developing meningitis
from a CSF leak, a reliable diagnostic tool to identify trace
amounts of CSF is required. Chemical identification of
glucose and protein is obsolete for this purpose (5, 6 ), but
␤2-transferrin assays are widely used. This protein is
detected by immunoblotting (7 ) or immunofixation and
silver staining (8 ), both of which are time-consuming and
labor-intensive. The immunoblot assay on the Hydrasys
LC takes 2–2.5 h and requires many manual steps. Moreover, interpretation of ␤2-transferrin electrophoresis is
complicated by the overlap of the application area and the
detection point for ␤2-transferrin. Finally, the main disadvantage is the interference of higher concentrations of
transferrin with the ␤2-transferrin band, which prevents
interpretation. No improvement is achieved by sample
dilution because ␤2-transferrin is diluted to concentrations below the detection limit.
Clinical Chemistry 50, No. 3, 2004
␤-Trace protein has been identified by rocket immunoelectrophoresis, which has a reported sensitivity of 91% in
diagnosing CSF leakage (4 ). For the automated assay
from Dade Behring, a range of 0.22–1.69 mg/L for healthy
individuals was reported, and a cutoff at 1.31 mg/L (97.5
percentile) was proposed (9 ). At concentrations between
1.31 and 1.69 mg/L, however, there is overlap of individuals without and patients with CSF leakage (9 ). In our
study, ␤-trace protein measured without predilution was
⬍1 mg/L in individuals without CSF leakage. In the
earlier study, nasal fluids were partly prediluted 1:100. At
a cutoff of 1 mg/L, the Dade Behring assay had a 100%
sensitivity (78 –100%; P ⬎0.05) and specificity (86 –100%; P
⬎0.05) for diagnosing a CSF leakage. Thus, in our opinion
the nephelometric quantification of ␤-trace protein is
preferable, particularly because this method is less timeconsuming and labor-intensive than the electrophoretic
method.
We gratefully acknowledge the excellent technical assistance of Jutta Breidenich and Ursula Emmler.
References
1. Ramsden JD, Corbridge R, Bates G. Bilateral cerebrospinal fluid rhinorrhea. J
Laryngol Otol 2000;114:137– 8.
2. Melegos DM, Freedman MS, Diamandis EP. Prostaglandin D synthase
concentration in cerebrospinal fluid and serum of patients with neurological
disorders. Prostaglandins 1997;54:463–74.
3. Felgenhauer K, Schädlich HJ, Nekic M. ␤-Trace protein as marker for
cerebrospinal fluid fistula. Klin Wochenschr 1987;65:764 – 8.
4. Bachmann G, Nekic M, Michel O. Clinical experience with ␤-trace protein as
a marker for cerebrospinal fluid. Ann Otol Rhinol Laryngol 2000;109:1099 –
102.
5. Oberascher G, Arrer E. Efficiency of various methods of identifying cerebrospinal fluid in oto- and rhinorrhea. ORL J Otorhinolaryngol Relat Spec
1986;48:320 –5.
6. Steedman, DJ. CSF rhinorrhea: significance of glucose oxidase strip test.
Injury 18 1985;5:327– 8.
7. Delaroche O, Bordure P, Lippert E, Sagniez M. Perilymph detection by
␤2-transferrin immunoblotting assay. Application to the diagnosis of perilymphatic fistulae. Clin Chim Acta 1996;245:93–104.
8. Ritchie RF, Smith R. Immunofixation I: general principles and applications to
agarose gel electrophoresis. Clin Chem 1976;22:497–9.
9. Arrer E, Meco C, Oberascher G, Piotrowski W, Albegger K, Patsch W. ␤-Trace
protein as a marker for cerebrospinal fluid rhinorrhea. Clin Chem
2002;48:939 – 41.
DOI: 10.1373/clinchem.2003.024158
Use of the Fetal Fibronectin Test in Decisions to Admit
to Hospital for Preterm Labor, Ellen F. Foxman* and Petr
Jarolim (Clinical Laboratory, Department of Pathology,
Brigham and Women’s Hospital, 75 Francis St., Boston,
MA 02115; * author for correspondence: fax 617-731-4872,
e-mail [email protected])
Early delivery attributable to preterm labor remains a
significant cause of neonatal morbidity and mortality.
Obstetricians often face the challenge of deciding whether
to admit a woman to the hospital when she presents with
possible preterm labor. In recent years, there has been
much emphasis on developing laboratory tests that can
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help clinicians predict the likelihood of “true” preterm
labor. The fetal fibronectin (fFN) assay has attracted
interest because of its reported high negative predictive
value for preterm labor. We implemented the Rapid Fetal
Fibronectin lateral immunodiffusion assay on the TLiIQTM
System (Adeza Biomedical) in the Brigham and Women’s
Hospital clinical laboratory in October 2001. To determine
how the test results would influence clinical decisionmaking in our hospital, we created a survey to be completed by clinicians at the time of test requisition. In this
report, we compare the survey results, which reflect the
pretest intention of the ordering clinicians, to the clinical
course of tested patients.
fFN, a uniquely glycosylated form of the abundant
plasma protein fibronectin, is found in the placenta and
amniotic fluid, primarily at the uteroplacental junction,
and is released into the upper vagina near the onset of
labor (1 ). Although the presence of fFN in vaginal fluids
does not necessarily indicate the onset of labor (positive
predictive value, 15–25%), its absence rules out labor
within 7 days with a very high negative predictive value
(97–99.5%) (1–3 ). Therefore, a negative result indicates a
low likelihood of delivery, but a positive test should not
be interpreted as an indication of labor or a reason for
admission.
From January to June 2002, all physicians requesting a
fFN test at Brigham and Women’s Hospital were asked to
complete a brief survey with the test requisition. On this
survey, the physician was asked to record the gestational
age of the fetus and the number of fetuses and to answer
the following question by circling any or all of four
possible responses: “I am sending a fFN test on this
patient, because a negative result will help me to avoid
one or more of the following interventions that I am
currently considering: (1) antenatal corticosteroids, (2)
admit to observation, (3) tocolysis, and (4) other”.
Institutional Review Board approval was obtained from
the Human Research Committee at Brigham and Women’s Hospital to review the medical records of patients
who received a fFN test during the study period. A total
of 245 tests were performed during this time period.
Gestational age was between 22 and 34 weeks for all of the
patients, with a mean maternal age of 26 years. We were
able to obtain relevant clinical data for 175 tests. Only
patients with singleton gestations (152 of 175 tests; 139
patients) were included in subsequent analyses. Twelve of
these patients received more than one fFN test during the
study period; only the first fFN test result was included in
the analysis. Of the 139 patients studied, we were able to
obtain survey results for 58 (42%).
Positive test rates were similar in the overall patient
population, in the subset of patients with clinical data,
and in the subset of patients with data and survey results
(⬃22%; Table 1A). The proportion of patients who delivered within 7 days and the test performance were
similar in the patients with clinical data (n ⫽ 139) and in
the subset with data plus survey results (n ⫽ 58). These
observations suggest that the smaller patient subset with
survey results is representative of the larger subset. Data