194 research outputs found
Practicable determination of the glomerular filtration rate (GFR) in dogs with a two-step-method
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Inhaltsverzeichnis
AbkĂŒrzungsverzeichnis
Einleitung
LiteraturĂŒbersicht
Material und Methoden
Ergebnisse
Diskussion
Zusammenfassung
Summary
Literaturverzeichnis
Danksagung
Lebenslauf
SelbstĂ€ndigkeitserklĂ€rungEinleitung Die FrĂŒherkennung von renalen Funktionsstörungen beim Hund noch im
subklinischen Bereich ist anhand klinischer Symptome und labordiagnostischer
Daten bisher nicht möglich. Daher besteht die Forderung nach einer möglichst
frĂŒhzeitigen Diagnostik der renalen Malfunktion, z. B. bei der unheilbaren und
progredient verlaufenden chronischen Niereninsuffizienz. Bisher existieren zur
Feststellung einer AzotĂ€mie sehr unterschiedliche Angaben fĂŒr Grenzwerte der
Serum-[Kreatininendo]. Material und Methoden Es wurden insgesamt n = 331 Hunde
beiderlei Geschlechts (mÀnnlich: n = 162 (48,9 %), weiblich: n = 169 (51,1 %))
im Alter von 7 (3,0 - 9,1) Jahren in die Untersuchungen einbezogen. Die Tiere
gehörten 57 verschiedenen Rassen an. Am hÀufigsten waren Mischlinge (n = 93
(28 %)) vertreten. FĂŒr die Ermittlung der Kreatinin - Wiederauffindungsrate
wurde das Substrat Kreatinin vergleichend entweder mit dem kinetischen
Farbtest nach Jaffé oder mit dem Enzym Kreatininase analysiert. Die Bestimmung
der GFR geschah mit dem renalen Funktionstest mittels P-CLterminal von
exogenem Kreatinin. Die Grenzwertbestimmung der Serum-[Kreatininendo] und die
qualitative GFR-Bestimmung erfolgten mittels der ROC-Analytik. Ergebnisse Im
Bereich bis 884 ”mol/l (10 mg/dl) betrug die Wiederauffindungsrate fĂŒr
Kreatinin im Hundeserum durchschnittlich 99,2 % bei der Jaffé-Methode und 99,4
% fĂŒr das enzymatische Verfahren. Im Bereich von 804 - 4.420 ”mol/l (9,1 - 50
mg/dl) wird die Kreatininkonzentration mit dem enzymatischen Verfahren um
durchschnittlich 1 - 2 % unterbewertet und mit der Jaffé - Methode
durchschnittlich um 3 - 4 % ĂŒberbewertet. Im Konzentrationsbereich von 804 -
4.420 ”mol/l ergaben sich bei der VerdĂŒnnung von 1:10 mit Aqua dest. eine
Wiederauffindungsrate fĂŒr die JaffĂ© - Methode von 87,7 % und fĂŒr das
enzymatische Verfahren von 97,7 %. Die mit einem renalen Funktionstest
ermittelte GFR der Probanden wurde mit insgesamt 25 verschiedenen
labordiagnostischen Blut- und Harnparametern verglichen (n = 89 Hunde). Erst
bei der stark reduzierten GFR auf †40 % der Norm bestanden fĂŒr einige
Parameter labordiagnostisch verwertbare VerÀnderungen vom jeweiligen
Referenzbereich. Von allen untersuchten Parametern korrelierte die
Serum-[Kreatininendo] am besten mit der GFR (n = 300 Hunde). Nach Ermittlung
der GFR der Tiere konnte der in der Literatur sehr unterschiedlich angegebene
Grenzwert fĂŒr die Serum-[Kreatininendo] neu festgelegt werden (n = 300 Hunde).
Er betrug 171 ”mol/l fĂŒr die Diagnostik der pathologisch erniedrigten GFR von
†30 % der Norm. Hierbei lagen die diagnostische SensitivitÀt bei
durchschnittlich 100 % und die SpezifitÀt bei 99 %. Als Kompromiss zwischen
der in der Praxis geforderten möglichst frĂŒhen Diagnostik der renalen
Malfunktion und einer noch ausreichenden diagnostischen QualitÀt wurde die GFR
†40 % der Norm gewÀhlt. Ab einem Grenzwert von 144 ”mol/l detektiert die
Serum-[Kreatininendo] diesen definierten Zustand der renalen Mafunktion. Die
diagnostische SensitivitÀt betrÀgt dann 89 % und die SpezifitÀt 97 %. Die
Verteilung von exogen zugefĂŒhrtem Kreatinin ist bei nierengesunden und
nierenkranken Hunden innerhalb von zwei Stunden abgeschlossen (n = 31
Hunde). Es wurde eine Vereinfachung des renalen Funktionstests zur
qualitativen Unterscheidung der Hunde in nierengesund (GFR > 70 %) und
nierenkrank (GFR †70 %) mit nur insgesamt zwei Blutproben untersucht (n =
89 Hunde). In den ZeitrÀumen 2 - 3 und 3 - 4 h nach der Applikation des
exogenen Kreatinins war eine qualitative Unterscheidung der Hunde nicht
möglich. Abweichend davon gelang mit den wesentlich spÀteren ZeitrÀumen, wie 6
- 7 und 7 - 7,5 h nach Markerzufuhr, die Bestimmung der beeintrÀchtigten
Nierenfunktion mit zufrieden stellender diagnostischer QualitÀt. Mit einer AUC
von 0,972 besaĂ die Serum-[Kreatiningesamt] im Zeitraum 7 - 7,5 h nach
Kreatiningabe die gröĂte diagnostische Sicherheit zur Unterscheidung der Hunde
in nierengesund und nierenkrank . Die Serum-[Kreatiningesamt] lieferte
eindeutig bessere Ergebnisse als die Serum-[Kreatininexo]. Eine
Blutprobenentnahme vor der Kreatininzufuhr ist bei dieser Art der
TestdurchfĂŒhrung ĂŒberflĂŒssig. Die ermittelte Grenze fĂŒr die
Serum-[Kreatiningesamt] liegt bei 270 ”mol/l. Zusammenfassend gilt fĂŒr Hunde,
deren Serum-[Kreatiningesamt] sich im Zeitraum 7 - 7,5 h nach entsprechend
dosierter Markerzufuhr noch im Bereich ĂŒber 270 ”mol/l befindet, dass sie eine
GFR von †70 % der Norm besitzen. Diese Tiere sind daher als nierenkrank zu
bezeichnen. Schlussfolgerungen \- Mit der Jaffé - Methode können
Kreatininkonzentrationen bis zu 2.600 ”mol/l (30 mg/dl) im Serum von Hunden
zuverlÀssig bestimmt werden \- Bei Serum - Kreatininkonzentrationen > 2.600
”mol/l (30 mg/dl) sollte die Bestimmung mittels enzymatischem Verfahren
erfolgen, eine VerdĂŒnnung der Probe ist nicht notwendig. \- Eine
FrĂŒhdiagnostik der renalen Malfunktion anhand der hier untersuchten 25
verschiedenen labordiagnostischen Parameter in Blut und Harn gelingt nicht mit
ausreichender diagnostischer Sicherheit und kann deshalb nicht empfohlen
werden. \- Zur Diagnose einer AzotÀmie mit der GFR von †40 % wird als obere
Grenze die physiologische Serum-[Kreatininendo] von 144 ”mol/l empfohlen.
Die diagnostische Sicherheit ist mit der SensitivitÀt von 89 % und der
SpezifitĂ€t von 97 % beachtlich hoch. \- Die Verteilung des exogen zugefĂŒhrten
Kreatinins ist sowohl bei nierengesunden als auch bei nierenkranken Hunden
innerhalb von zwei Stunden nach Markerzufuhr abgeschlossen. \- Zur
Vereinfachung der Bestimmung einer renalen Malfunktion können Hunde den Marker
exogenes Kreatinin in der Dosierung 2 g/m2 KOF i.v. bzw. s.c. oder in der
Dosierung 4 g/m2 KOF oral erhalten. Demnach ist im Zeitraum von 7 - 7,5 h eine
einmalige Blutprobe mit Bestimmung der Serum-[Kreatiningesamt] erforderlich.
Hunde mit einer Serum-[Kreatiningesamt] > 270 ”mol/l sind als nierenkrank
(GFR †70 % der Norm) einzustufen.Introduction The early determination of renal dysfunction in dogs on the basis
of clinical symptoms or laboratory diagnostic tests is difficult. There is
thus a need for a simple diagnostic test to determine renal dysfunction in the
early state, for instance in incurable and progressive renal failure.
Moreover, the establishment of an azotaemia in the dog has been difficult, due
to the variability of the upper reference value for the serum creatinine
concentration. Material and methods A total number of 331 dogs of both genders
(male: n = 162 (48.9 %), female: n = 169 (51.1 %)) and median age of 7 (3.0 -
9.1) years were included in the investigation. The dogs belonged to 57
different breeds; mixed-breed dogs (n = 93 (28 %)) were in the majority. For
the determination of the creatinine-recovery-rate, the substrate creatinine
was analysed either with the kinetic colour test of Jaffé or with the enzyme
creatininase. The GFR was determined with the renal function test using the
terminal plasma-clearance of exogenous creatinine. For the determination of
the limiting value and the qualitative determination of the GFR, the ROC-
analysis method was used. Results Up to 884 ”mol/l (10 mg/dl), the
determination rate for creatinine in the serum of dogs was on average 99.2 %
for the Jaffé-method and 99.4 % for the enzymatic method. In the range from
804 - 4,420 ”mol/l (9.1 - 50 mg/dl), the creatinine concentration was
underestimated by about 1 - 2 % with the enzymatic method and overestimated by
about 3 - 4 % with the Jaffé-method. If the serum was diluted 1 to 10 with
distilled water in the concentration range from 804 - 4,420 ”mol/l, there was
a determination rate of 87.7 % for the Jaffé method and 97.7 % for the
enzymatic method. The estimated GFR of each dog with the renal function test
was compared with 25 different laboratory blood- and urinary parameters (n =
89 dogs). Only when the GFR was reduced to below 40 % of the normal range were
there significant changes in some of the laboratory parameter. From all
measured parameters, the best correlation was between the endogenous serum-
creatinine concentration and the GFR (n = 300 dogs). These results for GFR in
the dogs allowed a new definition for the upper limit of the endogenous serum-
creatinine concentration. For GFR of 30% or less of the normal range this was
171 ”mol/l. The diagnostic sensitivity was 100% and the specificity 99%. As a
compromise between the earliest diagnosis of renal failure and a sufficient
diagnostic quality, a GFR of less than 40% of the reference range was chosen.
An upper limit of144 ”mol/l for the endogenous serum-creatinine concentration
detects this level of renal failure. The diagnostic sensitivity is 89% and the
specificity 97%. The distribution of exogenous creatinine is completed within
two hours in both normal and in dogs with renal disease. A simplification of
the renal function test to distinguish qualitatively between healthy and
diseased dogs using only two blood samples was tested (n = 89 dogs). In the
time interval between 2 - 3 h and 3 - 4 h after giving exogenous creatinine,
the qualitative differentiation between normal and diseased dogs was
impossible. However, the determination of reduced renal function is possible
with a satisfactory diagnostic quality at later times of between 6 - 7 h and 7
- 7.5 hours after giving creatinine. With an area under the curve (AUC) of
0,972, the total serum-creatinine concentration showed, in the time interval
between 7 - 7.5 h after giving creatinine the greatest diagnostic certainty in
the differentiation between healthy and diseased dogs. The total serum-
creatinine concentration showed better results than the exogenous serum-
creatinine concentration. For this test, a blood sampling before giving
creatinine is unnecessary. The estimated upper limit for the total serum-
creatinine concentration is 270 ”mol/l. In summary, dogs with a total serum-
creatinine of over 270 ”mol/l in the time interval 7 - 7.5 h after an exactly
dosed marker have a GFR †70 % of the normal range. These dogs have renal
disease. Conclusions \- With the Jaffé-method, creatinine concentrations up to
2,600 ”mol/l (30 mg/dl) can be measured reliably in the serum of dogs \-
Creatinine-concentrations over 2,600 ”mol/l should be determined with the
enzymatic method; a dilution is not necessary \- An early diagnosis of renal
dysfunction using 25 different laboratory parameters in blood and urine was
not possible with a sufficient diagnostic certainty.Such tests cannot be
recommended. \- For the diagnosis of an azotaemia with the GFR †40 %, the
physiological serum-creatinine concentration of 144 ”mol/l is recommended as
the upper limit. The diagnostic safety is high with a sensitivity of 89 % and
a specificity of 97 %. \- The distribution of the exogenous creatinine is
completed within two hours after marker application in both healthy and
diseased dogs. \- To simplify the determination of renal function, the dogs
received exogenous creatinine i.v. or s.c. in a dosage of 2 g/m2 body surface
area (BSA) or orally in a dosage of 4 g/m2 BSA. Only one blood sample for the
determination of the total serum-creatinine concentration in the time interval
between 7 - 7.5 h is necessary. Dogs with a total serum-creatinine
concentration > 270 ”mol/l are nephrologically sick (GFR †70 % of the
reference range)
The cultural adaptation of quantity judgment tasks in Ghanaian English and Akan
The phenomenon of mass and countability is multifaceted and has been controversially discussed in many disciplines. For linguistics, differences in the morphosyntactic marking of the distinction cross-linguistically, and its cross-cultural ontological-semantic conceptualization are particularly interesting. However, most studies into mass and countability have focused on (American) English, and, to some extent European and Asian languages. African languages and contexts have as yet been neglected by researchinto countability, and the methodological tools employed to study it do not account for the ambient cultural contexts. This paper presents the results of a quantity judgment task designed according to Barner and Snedekerâs (2005) experiment for American English speakers, conducted in Ghanaian English and Akan. The Ghanaian experiments reveal important concerns regarding the stimuli and their applicability, especially to Akan culture. Thus, inspired by other studies into the semantics of Akan, a new set of stimuli is suggested in order to investigate mass and countability contrastively in Ghanaian English and Akan. In this vein, they emphasize the insufficiency of translations with regard to (psycho)linguistic experiments and the importance of proper cultural adaptation
âFor explorers by explorersâ: A discursive analysis of cruise tourism in Norway
The Norwegian company Hurtigruten operates ships cruising along the Norwegian coast and has played an important role in tourism for over a century. This article provides a multimodal discourse analysis of the website advertising Hurtigrutenâs most popular journey, drawing on a critical tourism studies approach. It aims to answer the question as to what central themes emerge in tourism discourse on Norway, targeted at an international audience. Central characteristics of tourism discourse (Dann 1996), i.e., strangerhood, conflict, authenticity, and playfulness, are shown to be crucial in the analysed material. The paper discusses the notion of authenticity as a performative strategy in the promotion of Norwegian cruise tourism. One central aim of this paper is finding out what and how the notion of âauthentically Norwegianâ is advertised. The results imply that these topics, and especially the notion of authenticity, are aligned with general tourism imaginaries, which are similar globally.
 
Phonology of hunting signs in two Kalahari-Khoe speaking groups (Ts'ixa and ||Ani)
Phonology of hunting signs in two Kalahari-Khoe speaking groups (Ts'ixa and ||Ani
The presence of infection-related antiphospholipid antibodies in infective endocarditis determines a major risk factor for embolic events
AbstractOBJECTIVESThe impact of infection-associated antiphospholipid antibodies (APA) on endothelial cell activation, blood coagulation and fibrinolysis was evaluated in patients with infective endocarditis with and without major embolic events.BACKGROUNDAn embolic event is a common and severe complication of infective endocarditis. Despite the fact that APAs are known to be associated with infectious diseases, their pathogenic role in infective endocarditis has not been clearly defined.METHODSThe relationship among the occurrence of major embolic events, echocardiographic vegetation size, endothelial cell activation, thrombin generation, fibrinolysis and APA was examined in 91 patients with definite infective endocarditis, including 26 patients with embolic events and 65 control subjects without embolic events.RESULTSOverall, 14.3% of patients exhibited elevated APA levels. Embolic events occurred more frequently in patients with elevated levels of APA than in patients without (61.5% vs. 23.1%; p = 0.008). Patients with elevated levels of APA showed higher levels of prothrombin-fragment F1+2 (p = 0.005), plasminogen-activator inhibitor 1 (p = 0.0002), von Willebrand factor (p = 0.002) and lower levels of activated protein C (p = 0.001) than patients with normal levels of APA. Thrombin generation and endothelial cell activation were both positively correlated with levels of APA. The occurrence of elevated APA levels was frequently associated with structural valve abnormalities (p = 0.01) and vegetations >1.3 cm (p = 0.002).CONCLUSIONSInfection-associated elevated APA levels in patients with infective endocarditis are related to endothelial cell activation, thrombin generation and impairment of fibrinolysis. This may contribute to the increased risk for major embolic events in these patients
Involvement of the epidermal growth factor receptor in the modulation of multidrug resistance in human hepatocellular carcinoma cells in vitro
<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is a molecular complex tumor with high intrinsic drug resistance. Recent evidence suggests an involvement of the tyrosine kinase pathway in the regulation of ATP-binding cassette protein (ABC-transport protein) mediated multidrug resistance in cancer cells. The aim of this study was to examine whether EGFR inhibition sensitizes HCCs to chemotherapy and to elucidate its mechanism.</p> <p>Results</p> <p>Chemotherapeutic treatment induces multidrug resistance and significantly increases ABC-transport protein expression and function in a time- and dose-dependent manner in HCC cells. Furthermore, cytostatic treatment increases the mRNA expression of tyrosine kinases and induces the phosphorylation of ERK. EGF activation of the tyrosine kinase pathway up-regulated the ABC-transport protein mRNA expression and enhanced the survival of resistant HCC cells. Consistent with these effects, inhibition of the EGFR using siRNA decreased the ABC-transport protein mRNA expression and inhibited the proliferation of resistant cells. Additional treatment with Gefitinib, a clinically approved EGFR inhibitor, caused a dose-dependent reversal of resistance to conventional chemotherapy.</p> <p>Conclusion</p> <p>The present study demonstrates that the multidrug resistance of HCC is modulated through the EGF-activated tyrosine kinase cascade. Consequentially, the restoration of chemosensitivity by EGFR inhibition may lead towards new tailored therapies in patients with highly resistant tumors.</p
The Tinnitus Research Initiative (TRI) database: A new approach for delineation of tinnitus subtypes and generation of predictors for treatment outcome
Tinnitus, the phantom perception of sound, is a frequent disorder that causes significant morbidity and treatment is elusive. A large variety of different treatment options have been proposed and from most of them some patients benefit. However, a particular treatment that helps one patient may fail for others. This suggests that there are different forms of tinnitus which differ in their pathophysiology and their response to specific treatments. Therefore, it is a major challenge for tinnitus treatment to identify the most promising therapy for a specific patient
Development of a risk assessment tool for contact tracing people after contact with infectious patients while travelling by bus or other public ground transport: a Delphi consensus approach
Background: Tracing persons who have been in contact with an infectious patient may be very effective in preventing the spread of communicable diseases. However, criteria to decide when to conduct contact tracing are not well established. We have investigated the available evidence for contact tracing with a focus on public ground transport aiming to give guidance in what situations contact tracing should be considered. Methods: Relevant infectious diseases suitable for contact tracing in ground transport and a set of disease-specific epidemiological criteria were defined through literature search and structured multistep expert consultations. We developed continuous scales for each criterion to be rated for its relevance to contact tracing in ground transport. We used the Delphi method with an international expert panel to position the values of criteria on the respective scales. Results: The study led to the development of the âContact Tracing-Risk Assessment Profileâ (CT-RAP), a decision-making instrument, taking into account pathogen-specific as well as situation-specific criteria. This report describes the methodology of this instrument and presents two examples of ready-to-use CT-RAP for tuberculosis and for meningococcal disease in public ground transport. Discussion: The systematic and transparent use of the CT-RAP for tuberculosis and meningococcal disease is likely to facilitate reasonable, efficient and user-friendly decisions with respect to contact tracing. New CT-RAPs for additional pathogens and different settings such as schools and kindergartens are being planned
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