bluuebunny/crossref_metadata_2025_split huggingface dataset:
The diagnostic and clinical impact of the genetic variability of the S (surface) gene of hepatitis B virus / Diagnostische und klinische Relevanz der genetischen Variabilität des S- (surface) Gens des Hepatitis B Virus
Authors: Weber B. 
Published: August 2004

Abstract
The genetic variability of hepatitis B virus (HBV) represents
a challenge for the sensitivity of immunodiagnosis,
especially for the detection of surface antigen (HBsAg).
There are two types of variants of HBV. Naturally occurring
variants are the results of random changes selected
over years of population pressure. These variants include
HBV genotypes and unusual sequences, which may be
poorly detected by immunoassays. The selected variants
are mutants that arise in individuals under medically (vaccine,
hepatitis B immune globulin and antiviral therapy)
or naturally (chronic hepatitis B) induced immune pressure.
HBV S-gene mutants have been identified in successfully
immunized people worldwide. Based on the
assumption that current vaccines containing S protein do
not cross-protect against S gene mutants, a mathematical
model predicts the disappearance of wild-type HBV
in areas with HBsAg endemicity and the emergence of S
gene mutants in approximately 100 years as a consequence
of universal HBV vaccination. Mutant viruses
may escape detection by commercial HBsAg kits. There
are several reports on HBsAg negative carriers (HBV-DNA
positive) of S gene mutants with immunosilent
infection or "unusual" serologic constellations. Although
S gene mutants have been found to be associated with
a more severe clinical course of HBV infection and hepatocellular
carcinoma, the clinical significance of the
genetic variability of HBV genotypes and HBsAg mutants
needs to be further investigated. Detection of HBsAg
needs to be improved by the introduction of new HBsAg
assays able to recognize S gene mutants described so
far and with a lower detection threshold than current immunoassays in order to detect smallest amounts of
HBsAg in low-level carriers. There is also a need for more
complete epidemiological data on the prevalence of
HBsAg mutants in Western Europe and assays for the
(differential) screening of mutants need to be developed
and evaluated.
Die Situation des Qualitätsmanagements in Österreich / Quality Management in Austria
Authors: Schweiger Ch. R. 
Published: August 2004

Abstract
This article deals with the situation of quality management
in Austrian medical laboratories. Starting in 1994
after several rounds of discussion, the Society for Good
Analytical und Laboratory Practise (GALP) was founded
by the two major societies for laboratory medicine und
clinical chemistry. This society had the purpose to work
out strategies for quality management for Austrian medical
laboratories. The major outcome of the activities was
the adoption of ISO 9002:1994 as the model for quality
management in medical laboratories and the publication
of a guideline for the implementation of ISO 9002:1994
in the medical laboratories. This guideline was the basis
for many medical laboratories in Austria to seek ISO
9001/2:1994 certification. Currently most medical laboratories
(except those in hospitals, where certification is
not so prevalent) are ISO 9000 certified.
The next major development in quality management
was the adoption of the third medical device guideline of
the European Union (IVD-Guideline) and its national
implementation in the Austrian Law on Medical Devices.
This law includes several clauses, which can be used by
the ministry of health to require quality management systems
in medical laboratories and to establish rules for
certification agencies in this field. However, the implementation
of these clauses in the law is weak due to the
lack of resources on side of the ministry. Nevertheless,
European Union demands will lead to more effective
measures as they did in the field of clinical studies. The
development of EN ISO 15189:2003, which will be published
in German language in December 2003, will lead
to a change from certification to accreditation, at least in
the high quality segment of medical laboratories. This will
bring Austria in line with the international situation.
Currently, quality does not have any impact on reimbursement
of medical laboratories in Austria, so quality matters only in terms of cost but not in terms of higher
earnings. Therefore quality is motivated by idealistic factors
which tend to lose when economic pressures rise.
In the future, changes in this field will be necessary too.
Proteolytic degradation of cardiac troponin I does not influence the TOSOH
AIA-PACK cTnI 2G assay, a second generation test for the determination
of troponin I / Der proteolytische Abbau des kardialen Troponin I hat keinen Einfluss auf den TOSOH AIA-PACK cTnI 2G Assays,
ein Test der zweiten Generation zur Bestimmung des Troponins
Authors: Brinkmann T. , Götting C. , Kleesiek K. 
Published: August 2004

Abstract
We have evaluated the cardiac troponin I (cTnI) enzyme
immunoassay AIA-PACK cTnI 2G (Tosoh Bioscience).
The interassay precision at different cTnI levels (0.30
6.70 ng/ml-1) showed coefficients of variation (CV)
between 5.00% and 4.71% on the AIA 600 II instrument.
These data are in accordance with the functional sensitivity
(0.04 ng/ml-1) and analytical sensitivity (0.02 ng/ml-1) specified by the manufacturers.
Comparative troponin I measurements in serum samples
were performed on the AIA-600 II analyser (Tosoh
Bioscience) and the Dimension RxL analyser (Dade Behring).
The cTnI concentration of serum samples (n=226)
ranged from 0 ng/ml-1 to 114 ng/ml-1. Regression analysis
of the cTnI values obtained showed a close correlation
between both results (RxL=0.96 AIA+0.38;
r=0.960).
To induce proteolytic in vitro degradation of the cTnI
molecule, patient serum samples (n=20) were incubated
at 37C for 24 h and the cTnI concentration was determined
before and after the incubation with both analysers.
The cTnI concentration measured with the AIA-600
II analyser showed nearly identical values before and
after the incubation period. However, cTnI measured with the Dimension RxL analyser showed decreased cTnI values
in a range of 10 to 50% after the incubation period.
The AIA-PACK cTnI 2G assay uses two different monoclonal
antibodies against two epitopes in the proteolytic
stable region of the cTnI molecule (between position 40
and 90 of the cTnI amino acid sequence). Therefore,
measurement of cTnI in serum remains precise and specific in spite of in vitro proteolysis.
Evaluation of total Hepatitis C virus core antigen quantification / Evaluierung eines Tests zur Quantifizierung des Hepatitis C Kern Antigens
Authors: Hass I. , Stelzl E. , Haas J. , Marth E. , Kessler H. H. 
Published: August 2004

Abstract
Infections with hepatitis C virus (HCV) are pandemic. The
WHO estimates a worldwide prevalence of 3%. For monitoring
of chronic hepatitis C, assays for direct virus
detection are employed. In this study, an improved version
of the Ortho® trak-C assay™ (Ortho-Clinical Diagnostics,
Raritan, NJ) for detection of the HCV core
antigen was evaluated. Precision, interassay, and intraassay
variation were determined and a total of 115 clinical
specimens were investigated. When precision of the
Ortho® trak-C assay™ was evaluated, the assay gave
positive results in those samples above the expected
detection limit. Interassay coefficients of variation ranged
between 6–25%, while intra-assay coefficients of variation
were found to be between 19%. When clinical samples
were tested with the Ortho trakC assay and
compared with results obtained with the Cobas Ampli
Prep/Cobas Amplicor HCV Monitor Test (Roche Molecular
Systems, Inc., Branchburg, NJ), 66% of all positive
values were found to be within a +-0.5 log difference of
the level obtained with the molecular assay. In conclusion,
the Ortho® trak-C™ assay showed a good test performance
and proved to be suitable for the
routine-diagnostic laboratory.
Can CA19-9 kinetics replace imaging procedures in response evaluation
of patients undergoing chemotherapy for metastatic pancreatic cancer? / Kann die Kinetik des CA19-9 bei der Response-Evaluation von chemotherapeutisch behandelten
Patienten mit metastasierendem Pankreaskarzinom bildgebende Verfahren ersetzen?
Authors: Stemmler H. J. , Stieber P. , Heinemann V. 
Published: August 2004

Abstract

Background: Response evaluation by standard imaging
procedures such as computed tomography (CT) may be
difficult in patients undergoing chemotherapy for
advanced and metastatic pancreatic cancer. The aim of
the study was to determine whether kinetics of CA19-9
levels can replace imaging procedures in evaluating the
response to chemotherapy in these patients.

Patients and methods: Patients with advanced or
metastatic pancreatic cancer were included in the study.
Patients received a combination chemotherapy consisting
of gemcitabine (1000 mg m−2 d1, 8, 15) and cisplatin
(50 mg m−2 d1, 15) repeated on day 29. Treatment was
continued until unacceptable toxicity or disease progression
occurred. CA19-9 levels were measured directly
before each cytotoxic treatment cycle. CA19-9 response
was defined by a ≥50% decrease in CA19-9 serum levels
within two months after treatment initiation.

Results: A total of 77 patients with initially elevated
CA19-9 levels were included for evaluation (f/m = 26/61;
stage 3/4 = 24/63). Out of 15 patients who had responded
to chemotherapy regarding imaging criteria (CR 4, PR
11, OR 19.5%), 14 patients were classified as CA19-9
responders. Although 62 patients had not responded to
chemotherapy by CT-imaging criteria, 29 patients fulfilled
the criterion of a CA19-9 responder. The low value of
CA19-9 kinetics in predicting imaging results (positive
predictive value 32.5%) seems to be clinically irrelevant
since CA19-9 responders, independent of imaging criteria,
have a significant improvement of survival time
compared to non-responders (295 days; 95%CI:
285–445 vs 174 days; 95%CI: 134–198; p = 0.022).

Conclusion: CA19-9 kinetics are unable to predict
tumor response regarding imaging criteria. However, the
kinetic of CA19-9 in a patient undergoing chemotherapy
for pancreatic cancer seems to be a reliable indicator in
predicting survival.
Ist die Tumormarker-Profilauswertung wirklich (fuzzy) logisch? / Is the analysis of tumor marker profiles (fuzzy) logical?
Authors: Bitterlich N. 
Published: August 2004

Abstract
Fuzzy-based procedures of multiparametric pattern recognition
have been established in technical diagnostics and industrial automation for more than 10 years. The
consideration of fuzziness has broken new ground in
computer-aided decision support which still goes on
successfully today. The capability of this methodology
significantly benefits from the inclusion of knowledge,
experience, and applied examples. A further advantage
of these procedures consists in the terminological transparency
and ease of comprehension. Instead of abstract
mathematical formulas, the algorithms are described by
verbal rules. This aspect particularly facilitates the interdisciplinary
cooperation between users and mathematicians,
and in this way facilitates a time- and cost-effective
system development as well.
However, the utilization of fuzzy systems is effectual
only if the problem is suitable for fuzzy treatment. As an
example, these requirements are examined in the analysis
of tumor marker profiles. The illustration of basic ideas
and principles provides the understanding of the
mathematical data evaluation without direct confrontation
with algorithms. As a result, an increase of sensitivity
on high specificity is achievable. The particular steps of
calculation seem to conform to the subjective decision
making when tumor markers are analyzed.
Diagnostik von Hypophysenadenomen / Diagnostics of pituitary adenomas
Authors: Klingmüller D. , Saller B. , Quabbe H.-J. 
Published: August 2004

Abstract
Pituitary adenomas are rare benign tumors with delayed
manifestation which can include headaches and symptoms
of nerve compression, such as visual field disturbances
or endocrine dysfunction. Endocrine abnormalities
can be the result of overproduction of pituitary
hormones, pituitary insufficiency, or a combination of
both. The evaluation of suspected pituitary tumors
should include the determination of the presence and
type of hormone hypersecretion as well as hyposecretion,
combined with pituitary imaging. Screening for pituitary
dysfunction is achieved by assessing the pituitary
and target hormone concentrations in blood, maybe followed
by dynamic tests of the pituitary function.
Diagnostik des Wachstumshormonmangels und des Wachstumshormonexzesses
(Akromegalie) / Diagnostics of growth hormone deficiency and excess (acromegaly)
Authors: Herrmann B. L. , Mann K. , Janssen O. E. 
Published: August 2004

Abstract
Growth hormone (GH) is synthesized in the anterior lobe
of the pituitary gland and has a plasma half-life of
19 minutes. GH-secretion is regulated by hypothalamic
releasing hormone (GHRH) stimulation and somatostatin
inhibition. The major effect of GH is the stimulation of
insulin-like growth factor-1 (IGF-1) synthesis and secretion
by the liver. However, GH also has other biological
effects through other mediators. Serum-IGF-1 is bound
to IGF binding protein-3 (IGFBP-3) and to acid-labile
subunit (ALS). The GH/IGF-1-axis is evaluated when
either GH-deficiency (GHD) or GH-excess (acromegaly)
are suspected. GHD is confirmed by a diminished GHresponse
to insulin-induced hypoglycemia (normal range
GH >5 μg/l) or to administration of GHRH+arginine
(normal range GH >9 μg/l). Acromegaly has distinct clinical
signs and is confirmed when GH can not be suppressed
below 1 μg/l by an oral glucose tolerance test
in combination with elevated IGF-1 levels adjusted for
age.
Primary aldosteronism: Diagnosis and differential diagnosis / Primärer Hyperaldosteronismus: Diagnose und Differentialdiagnose
Authors: Schirpenbach C. , Seiler L. , Beuschlein F. , Reincke M. 
Published: August 2004

Abstract
Primary aldosteronism, characterized by hypertension
and low-to-normal potassium levels, has lately been recognized
as a rather frequent cause of secondary hypertension.
The two principle reasons for primary
aldosteronism are bilateral adrenal hyperplasia and
aldosterone-producing adenoma. Screening for primary
aldosteronism is performed by measuring the aldosterone/
renin ratio, which has good accuracy even if the
patient is under medication. The diagnosis needs to be
confirmed by further diagnostic procedures and, since
the therapy of the subtypes varies, differential diagnosis
is required. Bilateral adrenal hyperplasia is treated
through medication, whereas hypertension due to adenoma
can be cured or improved by adrenalectomy.
Aviditätsuntersuchungen spezifischer IgG in Seren von Syphilispatienten / Investigations of avidity of specific IgG in sera of patients with syphilis
Authors: Blatz R. , Kruppa A. , Rodloff A. C. 
Published: August 2004

Summary

Background: Syphilis is among the infections that are
characterized best by serologic methods. Nevertheless,
in single cases evaluation may be difficult. The aim of
this study was to investigate the avidity of specific IgG
to achieve additional information.

Patients and methods: In 182 previously analyzed
sera from syphilitic patients the avidity of Treponema pallidum-
specific IgG was estimated by means of ELISA
(endpoint detection).

Results:
Treponema pallidum-specific IgG reached
postinfectious avidity values of 20% after about four
weeks and of 40% after six months without therapy. Values
above 60% could be detected only in special cases.
Between avidity and specific IgM–but not avidity and
Cardiolipin microflocculation test -, a reverse proportional
relationship exists. Persistence of specific IgM is evidenced
by the avidity values.

Conclusions: Avidity detection of specific IgG gives
evidence of the time of primary infection. The estimation
of avidity besides conventional diagnostics in syphilis
may confirm cases suspected of reinfections, give additional
information in problematic cases or in cases for an
expert's certificate.
Anwendung der HPLC-Tandem-Massenspektrometrie in der klinischen Chemie / The use of HPLC-tandem mass spectrometry in clinical chemistry
Authors: Vogeser M. 
Published: August 2004

Abstract
The technology of liquid chromatography-tandem mass
spectrometry opens the perspective of a more widespread
use of highly specific mass spectrometric assays
in a routine clinical laboratory setting as compared to gas
chromatography-mass spectrometry. After the first years
of routine application of liquid chromatography-tandem
mass spectrometry in a growing number of laboratories,
it has become evident that this technique will become a
substantial part of the methodological spectrum of laboratory
medicine. This is due to the very wide range of
potential analytes to be measured with no limitation by
molecular mass, the straightforward sample preparation
not requiring chemical derivatization and due to the rugged
instrumentation with limited maintenance requirements.
This review gives a survey of the technical
principles of liquid chromatography-tandem mass spectrometry,
describes the basics of method development
and typical routine applications, discusses strengths and
limitations of the technique, and highlights the perspectives
for future developments of the technology.
Genexpressionsanalysen bei akuten Leukämien: Diagnostik der Zukunft? / Gene expression profiling in acute leukemia: diagnostics of the future?
Authors: Haferlach T. , Kohlmann A. , Schnittger S. , Dugas M. , Kern W. , Schoch C. 
Published: August 2004

Abstract
A comprehensive diagnosis in leukemia relies on a
combination of several methods. Cytomorphology, cytochemistry,
cytogenetics, fluorescence in situ hybridization,
multiparameter flow cytometry, and molecular
methods are applied in parallel. Recently, gene expression
profiling using microarrays has made it possible to
measure the expression of thousands of genes in one
step. The respective specific signature leads to a molecular
fingerprint of the tumor sample. Therefore, gene
expression profiling may lead to a better molecular classification,
insights into pathophysiology of malignant and
benign diseases as well as to new treatment options.
This can be approached best by using well-defined
tumor subtypes. Thus, leukemias are a very informative
model system. Furthermore, gene expression profiling
may lead to new targeted therapies and can detect genes
to be used for minimal residual disease studies. Very
recent studies also mention the possibility of using gene
expression profiling for prognostication. In conclusion,
microarrays may lead to a single platform for leukemia
diagnosis with quick and very robust and even cheaper
results. Therefore, this new method should be further validated
in parallel to the standard work-flow and has to
be proven before substituting other methods in the
future.
Patientennahe Laboratoriumsdiagnostik (Point-of-Care-Testing): Empfehlungen zum Einsatz von unterschiedlichem Probenmaterial für die Diagnostik des Diabetes mellitus / Bedside testing in laboratory diagnostics (point-of-care testing): recommendations for the use of different testing materials in the diagnostics of Diabetes mellitus
Authors: Haeckel R. , Hänecke P. , Koschinsky T. , Luppa P. , Schlebusch H. , Wahl H. G. 
Published: August 2004

Abstract
Besides venous plasma exclusively recommended by the
WHO other five sample systems are used for the diagnostics
of glucose intolerance particularly at point-of-care
testing. It appears problematic to use conversion
factors for the calculation of different decision limits if
these are derived from those limits determined for
venous plasma. It therefore seems urgently required to
agree on only one sample system.
Qualitätssicherung der patientennahen Sofortdiagnostik (Point-of-Care-Testing) im Krankenhaus: Muster für eine hausinterne Richtlinie / Quality assurance in bedside testing at the hospital: sample guidelines for internal use
Authors: Hänecke P. , Haeckel R. , Koschinsky T. , Luppa P. , Schlebusch H. , Wahl H. G. 
Published: August 2004

Abstract
The following recommendations are based on the
instructions of the “Richtlinie der Bundesärztekammer
zur Qualitätssicherung quantitativer laboratoriums-medizinischer
Untersuchungen” according to the decision of
the executive board of the Bundesärztekammer (RiliBäk)
as of August 24th 2001. They have exemplary character
for hospitals in which the internal quality control of point-of-care testing is under the responsibility of the central
laboratory. The recommendations focus on blood glucose,
but are also applicable to other analytes with only
slight modifications.
Das pränatale/frühkindliche Immunsystem und Allergie – Ergebnisse humaner und tierexperimenteller Studien / Prenatal and early postnatal immune system and allergy – outcomes of human and animal studies
Authors: Blümer N. , Herz U. , Renz H. 
Published: August 2004

Abstract
Based on epidemiological and clinical observations there
is strong evidence for a prenatal and early postnatal
priming of allergic diseases. The pregnant mother in her
specific environment influences the allergic development
of her offspring considerably. Certain living conditions
(high microbial exposure, probiotic nutrition) during pregnancy
and in the early postnatal living period were identified
as protective for the development of allergies (hay
fever, asthma, atopic dermatitis). Nevertheless, these epidemiological
and clinical studies are only able to find
associations between the maternal environment and the
allergic phenotype of the child. It is not possible to show
a direct causal relationship between the maternal
immune status and the development of allergies in the
child. Therefore, it is mandatory to analyze this relationship
using animal experiments. First animal studies try to
implicate the maternal immunity in the allergic development
in the neonate. The development of the neonatal
immune system was analyzed after modulation of the
maternal immune system. Sensitized mouse mothers
influence the adaptive immune system of the neonate
essentially. This is true for the T-cell mediated immune
response as well as the B-cell mediated antibody
response. Maternal sensitization (OVA, Der p1) inhibits,
for example, a specific anti-IgE response in the neonates
to the same allergen. Treatment of these neonates of
sensitized mothers with a heterologous allergen does not
alter the specific anti-IgE response. Using this mouse
model it was possible to show that an experimentally
induced asthmatic phenotype of the mouse mother could
be transmitted to the neonate. These results of human
and animal studies clearly demonstrate that the maternal
immune status influences the development of the neonatal
immune system. For future therapeutical strategies
of allergy prevention, the described results could be very
helpful.
Topical immunomodulators in the treatment of atopic dermatitis / Topische Immunmodulatoren bei der Behandlung der atopischen Dermatitis
Authors: Breuer K. , Kapp A. , Werfel T. 
Published: August 2004

Abstract
Atopic dermatitis is a chronic inflammatory skin disease
that often begins in early infancy and runs a course of
exacerbation and remission. Over the last decades topical
corticosteroids have represented the therapy of
choice for the treatment of flares. However, due to potential
side effects, topical steroids are not generally accepted
by the patients and physicians. The macrolides
tacrolimus and pimecrolimus exert their immunomodulatory
effects via inhibition of the phosphatase calcineurin,
which normally dephosphorylates the transcription
factor NF-AT in T-lymphocytes. This leads to a decreased
transcription of several proinflammatory cytokines. Moreover,
the immunomodulators have shown to influence
also mast cells and antigen presenting cells. The proinflammatory
effect of Tacrolimus and Pimecrolimus
could be confirmed in various clinical studies on children
and adult patients with atopic dermatitis. Various reports
demonstrate a potential clinical effect also in other cutaneous
skin diseases.