The utility of a specific hepatic CYP-3A4 probe (C14-Erythromycin breath test [EBT]) versus the general CYP-P450 probe (antipyrine clearance [ACL] test), for the prediction of docetaxel (D) pharmacokinetics (PK)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2523-2523
Author(s):  
M. Michael ◽  
R. J. Booth ◽  
A. Milner ◽  
A. Hatzamihallis ◽  
P. Francis ◽  
...  
Keyword(s):  
Breath Test ◽  
Drug Disposition ◽  
Serum Levels ◽  
Individual Variability ◽  
Exhaled Breath ◽  
Antipyrine Clearance ◽  
Advanced Malignancy ◽  
Erythromycin Breath Test ◽  
The Individual ◽  
Clearance Test

2523 Background: BSA-based cytotoxic dosing does not account for the individual variability in drug disposition. In the case of D, CYP 3A4 probes such as the EBT have been assessed to individualise dosing, but inconsistently. This report is the first study comparing the EBT directly with the widely available general P450 probe, the ACL test, for the prediction of D PK when given either q 21 days or weekly. Methods: Patients (pts) with pre-treated advanced malignancy suitable for D therapy, Se bilirubin≤1.0xUNL, AST≤1.5xUNL & ALP≤2.5xUNL, were entered. Prior to D therapy, pts underwent EBT and ACL test. Pts were given IV 14C N-methyl-erythromycin and exhaled breath samples were captured for 14CO2 from 5–120 mins post. The EBT parameters determined: 14CO2 flux at 10 min (CO2f10), & 20 min (CO2f20), (iii) terminal rate constant kCO2 (iv) AUCCO2,(0-∞) & AUCCO2,(0–60). For the ACL test, pts was given oral antipyrine 10mg/kg, blood samples were collected from 0, 4 & 24 hrs post, and serum levels measured: ACL was calculated as per Farrell et al.(Br J Clin Pharmacol 18:559). D was given 75mg/m2 q21 days or 35mg/m2 weekly. Samples taken for D PK in course 1 day 1, parameters included: half life (tD1/2), & clearance (CLD). Correlations were sought between EBT parameters, ACL values and D PK parameters. Results: 20 pts accrued, M:F= 12:8, Median age= 65. Mean BSA = 1.77m2 (1.44–2.07). D q21 days:D weekly= 13:7. EBT parameters (N= 19) (Mean, [CV%]): CO2f10 (%/min) 0.051 (106), CO2f20 0.052 (82), kCO2 (min- 1) 0.007 (22), AUCCO2,(0-∞) 7.9 (85), AUCCO2,(0–60) 2.64 (81). ACL (N=19) (ml/min); 35.8 (37). No significant differences observed for EBT parameters and ACL between the q21 days vs weekly dosing. D PK parameters (N=19): CLD (l/hr) 57.2 (36), tD1/2 (hrs) 12.7 (33). No correlations were observed between the D PK and EMBT parameters for all pts and regardless of the regimen given. For D weekly pts, a significant linear relationship was observed between CLD and ACL (P =0.007, R2= 79.47%). Conclusions: The utility of EBT for the prediction of D PK was not confirmed in this study. The Antipyrine Clearance test may be superior in this regard for D, but regimen dependent and hence warrants further evaluation. No significant financial relationships to disclose.

THE STUDY OF THE INDIVIDUAL VARIABILITY OF THE LINEAR DIMENSIONS OF THE SPHENOID SINUS

2019 ◽  
Vol 21 (1) ◽  
pp. 64-70
Author(s):  
O.V. Mareev ◽  
◽  
G.O. Mareev ◽  
M.E. Gutynina ◽  
D.A. Maksimova ◽  
...  
Keyword(s):  
Sphenoid Sinus ◽  
Individual Variability ◽  
Linear Dimensions ◽  
The Individual

scholarly journals Untargeted Molecular Analysis of Exhaled Breath as a Diagnostic Test for Ventilator-Associated Lower Respiratory Tract Infections (BreathDx)

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217362
Author(s):  
Pouline MP van Oort ◽  
Tamara M Nijsen ◽  
Iain R White ◽  
Hugo H Knobel ◽  
Timothy Felton ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Infections ◽  
Breath Test ◽  
Gas Chromatography Mass Spectrometry ◽  
Exhaled Breath ◽  
Lower Respiratory Tract Infections ◽  
Exhaled Breath Analysis ◽  
Registration Number ◽  
Tract Infections

Patients suspected of ventilator-associated lower respiratory tract infections (VA-LRTIs) commonly receive broad-spectrum antimicrobial therapy unnecessarily. We tested whether exhaled breath analysis can discriminate between patients suspected of VA-LRTI with confirmed infection, from patients with negative cultures. Breath from 108 patients suspected of VA-LRTI was analysed by gas chromatography-mass spectrometry. The breath test had a sensitivity of 98% at a specificity of 49%, confirmed with a second analytical method. The breath test had a negative predictive value of 96% and excluded pneumonia in half of the patients with negative cultures. Trial registration number: UKCRN ID number 19086, registered May 2015.

scholarly journals Individual variation of the masticatory system dominates 3D skull shape in the herbivory-adapted marsupial wombats

2019 ◽  
Author(s):  
Vera Weisbecker ◽  
Thomas Guillerme ◽  
Cruise Speck ◽  
Emma Sherratt ◽  
Hyab Mehari Abraha ◽  
...  
Keyword(s):  
Individual Variation ◽  
Principal Component ◽  
Individual Variability ◽  
Shape Variation ◽  
Mandibular Ramus ◽  
Geometric Morphometric ◽  
Skull Shape ◽  
Marsupial Species ◽  
Masticatory System ◽  
The Individual

AbstractBackgroundWithin-species skull shape variation of marsupial mammals is widely considered low and strongly size-dependent (allometric), possibly due to developmental constraints arising from the altricial birth of marsupials. However, species whose skulls are impacted by strong muscular stresses – particularly those produced through mastication of tough food items – may not display such intrinsic patterns very clearly because of the known plastic response of bone to muscle activity of the individual. In such cases, shape variation should not be dominated by allometry; ordination of shape in a geometric morphometric context through principal component analysis (PCA) should reveal main variation in areas under masticatory stress (incisor region/zygomatic arches/mandibular ramus); but this main variation should emerge from high individual variability and thus have low eigenvalues.ResultsWe assessed the evidence for high individual variation through 3D geometric morphometric shape analysis of crania and mandibles of thre species of grazing-specialized wombats, whose diet of tough grasses puts considerable strain on their masticatory system. As expected, we found little allometry and low Principal Component 1 (PC1) eigenvalues within crania and mandibles of all three species. Also as expected, the main variation was in the muzzle, zygomatic arches, and masticatory muscle attachments of the mandibular ramus. We then implemented a new test to ask if the landmark variation reflected on PC1 was reflected in individuals with opposite PC1 scores and with opposite shapes in Procrustes space. This showed that correspondence between individual and ordinated shape variation was limited, indicating high levels of individual variability in the masticatory apparatus.DiscussionOur results are inconsistent with hypotheses that skull shape variation within marsupial species reflects a constraint pattern. Rather, they support suggestions that individual plasticity can be an important determinant of within-species shape variation in marsupials (and possibly other mammals) with high masticatory stresses, making it difficult to understand the degree to which intrinsic constraint act on shape variation at the within-species level. We conclude that studies that link micro- and macroevolutionary patterns of shape variation might benefit from a focus on species with low-impact mastication, such as carnivorous or frugivorous species.

A low dose (6.5 mg) of intravaginal DHEA permits a strictly local action while maintaining all serum estrogens or androgens as well as their metabolites within normal values

2017 ◽  
Vol 29 (2) ◽  
Author(s):  
Fernand Labrie ◽  
Céline Martel
Keyword(s):  
Sex Steroids ◽  
Low Dose ◽  
Normal Values ◽  
Serum Levels ◽  
Local Action ◽  
Serum Concentrations ◽  
Efficacy And Safety ◽  
Vulvovaginal Atrophy ◽  
Clinical Program ◽  
The Individual

AbstractObjective:Serum concentrations of estradiol (EMethods:Serum EResults:No biologically significant change in the individual serum concentrations of EConclusion:While the clinical program on vulvovaginal atrophy has shown the efficacy and safety of intravaginal 6.5 mg of DHEA (prasterone), the present data illustrate in detail the serum levels of the individual sex steroids and their metabolites derived from DHEA. The data obtained are in line with the physiology of intracrinology and confirm an action limited to the vagina as the serum concentrations of all sex steroids are maintained within the normal values of menopause, thus protecting the uterus and most likely other tissues.

scholarly journals Comparison of urinary 6-β-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity

1992 ◽  
Vol 52 (3) ◽  
pp. 265-273 ◽  
Author(s):  
Paul B Watkins ◽  
D Kim Turgeon ◽  
Paul Saenger ◽  
Kenneth S Lown ◽  
Joseph C Kolars ◽  
...  
Keyword(s):  
Breath Test ◽  
Cyp3a Activity ◽  
Erythromycin Breath Test

Diagnosis of Helicobacter pylori Infection by Means of Reduced-Dose 13C-Urea Breath Test and Early Sampling of Exhaled Breath

2013 ◽  
Vol 57 (5) ◽  
pp. 607-611 ◽  
Author(s):  
Sylmara L.M. Pacheco ◽  
Silvio K. Ogata ◽  
Rodrigo S. Machado ◽  
Francy Reis da Silva Patrício ◽  
Mario L.E. Pardo ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Breath Test ◽  
Urea Breath Test ◽  
Helicobacter Pylori Infection ◽  
Exhaled Breath ◽  
Reduced Dose ◽  
13C Urea Breath Test

scholarly journals GENDER FEATURES OF THE ALVEOLAR PROCESS OF THE UPPER JAW

2020 ◽  
Vol 19 (4) ◽  
pp. 10-14
Author(s):  
Z. Masna
Keyword(s):  
Morphological Characteristics ◽  
Individual Variability ◽  
Functional Restoration ◽  
Occlusal Plane ◽  
Dental Arch ◽  
Alveolar Process ◽  
Dental Examination ◽  
Upper Jaw ◽  
The Individual ◽  
Alveolar Arch

The individual face shape, the ratio of its proportions, the articulation capabilities of each person to a significant extent depend on the characteristics of occlusion and occlusion, in turn, are determined by the size, shape and ratio of dental, alveolar and basal arches. Two of them - alveolar and basal - pass at the corresponding levels of the alveolar areas of the jaws, which means that it is almost impossible to correct them, therefore they play the role of landmarks for setting the dental arch during dental prosthetics. A full-fledged aesthetic and functional restoration of the maxillofacial region after prosthetics largely depends on the dentist taking into account the individual morphological characteristics of the jaws, their cellular areas and specifically the morphometric parameters of the collar and basal arches. In order to determine the possible variants of the shape of the alveolar and basal arches of the upper jaw and the patterns of their ratio during the routine dental examination, 55 people (27 men and 28 women) aged 21-60 years with preserved maxillary dentition were examined. It has been established that the alveolar and basal arches of the upper jaw can have the shape of five geometric shapes: an oval, a semicircle, an ellipse, a trapezoid or a square. In this case, the shape of the collar and basal arches can coincide or be combined in various combinations. The analysis of the obtained results showed that in men the alveolar arch most often had the shape of an oval (70%), in women - an oval or semicircle (43%, respectively). With the aim of possible variants of the alveolar and basal arches form determination and peculiarities of their correlation 55 individuals (27 men and 28 women) in age of 21-60 years with the preserved teeth row were examined during planned dental examination. All examined were patients of the “Dental clinic of dr. Dakhno” (Kyiv). Computer tomographic investigation was made to these patients according to medical indications, scanning was made parallely to the occlusal plane. Image reconstruction was conducted with the use of highly dimentional bone algorithm. Alveolar and basal arch form of the upper jaw were determined on the images. It was established that alveolar and basal arches of the upper jaw can have a form of five geometrical figures: oval, semicircle, ellipse, trapeze or square. Form of the alveolar and basal arches can match or can combine in different combinations. Received results analysis testified that alveolar arch has a form of the oval in men and oval or semicircle – in women. Basal arch in men also most frequently has a form of oval, less often – semicircle, square and trapeze. In women basal arch more often has a form of trapeze or semicircle, less often – oval or square. In men alveolar and basal arches form matched in 41% of cases, in women – only in 31% of cases among total amount of all examined individuals. Most often alveolar and basal arches matched in the form of oval and semicircle, only in one case arches of the trapeze form matched in man, in woman – square form. Maxillary alveolar and basal arches form variants analysis let to determine areas, where distance between alveolar crests was maximal. Most variable this index was in individuals with the oval form of the alveolar arch on the level of 16-26, 17-27 or 18-28 teeth. Peculiarities of the alveolar and basal arches form of the alveolar process of the upper jaw in male and female individuals are characterized with expressed individual variability. These peculiarities consideration during dental prosthesis let avoid series of complications connected with the pressure redistribution on the osseous tissue of the jaws during articulation. 

scholarly journals Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease

Toxins ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 520 ◽  
Author(s):  
Shanmugakumar Chinnappa ◽  
Yu-Kang Tu ◽  
Yi Chun Yeh ◽  
Griet Glorieux ◽  
Raymond Vanholder ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Dysfunction ◽  
Serum Levels ◽  
Significant Negative Correlation ◽  
Cross Sectional Study ◽  
Left Ventricular ◽  
Uremic Toxins ◽  
Cross Sectional ◽  
The Individual

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.

Biologic effects of recombinant human interleukin-3 in vivo.

1991 ◽  
Vol 9 (12) ◽  
pp. 2120-2127 ◽  
Author(s):  
A Lindemann ◽  
A Ganser ◽  
F Herrmann ◽  
J Frisch ◽  
G Seipelt ◽  
...  
Keyword(s):  
Interleukin 2 ◽  
Serum Levels ◽  
Immunoglobulin M ◽  
Acute Phase Reactants ◽  
Advanced Malignancy ◽  
Interleukin 3 ◽  
Reactive Protein ◽  
Biologic Effects ◽  
In Vivo Effects

The biologic in vivo effects of recombinant human interleukin-3 (rhIL-3) were assessed in a phase I clinical study of 30 patients with advanced malignancy. On day 1 rhIL-3 was administered by a single intravenous (IV) bolus injection, followed by subcutaneous (SC) injections once daily from day 2 to 15; at least three patients were treated at each dose level (60, 125, 250, and 500 micrograms/m2). A transient decrease of eosinophil and monocyte counts was observed immediately after IV injection of rhIL-3, whereas the neutrophil count remained unaffected. Total WBC counts and neutrophil counts increased dose dependently up to threefold, whereas a 10-fold to 50-fold rise was observed in levels of circulating eosinophils and basophils. Platelet counts increased up to twofold. Patients developed moderate increases of serum levels of soluble interleukin-2 receptors, beta 2-microglobin, and immunoglobulin M (IgM), and of the acute phase reactants, C-reactive protein (CRP), fibrinogen, and haptoglobin. An increase in interleukin-6 (IL-6) serum levels was detected in patients treated by IV bolus rhIL-3. The serum half-life of IV injected rhIL-3 was 20 +/- 3 minutes; after SC administration, 210 +/- 15 minutes. Administration of rhIL-3 was generally well tolerated, with mild fever, headache, and local reactions at the injection site being the most frequent side effects. The primary course of the underlying malignant diseases was not significantly altered by administration of rhIL-3. The results indicate that rhIL-3 acts in vivo as a multilineage hematopoietic growth factor and a weak inflammatory mediator that may be used successfully to improve states of hematopoietic failure.

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