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Biomedical subjects

A Eberhard

Publications and source records attributed to A Eberhard.

At least 19 recordsLinked to original sources

[Mechanisms of resistance to sexual transmission of HIV-1].

Sexual transmission is the most common pathway for HIV-1; nevertheless some individuals remain seronegative despite repeated high risk sexual exposure. These were grouped in cohorts of "highly exposed but persistently seronegative" individuals, mostly prostitutes and flailing couples. Three lines of defence were observed in these cohorts. The first one is the mucosal barrier, the determining factors of which are the type of epithelium (monolayer or multilayer), epithelial integrity, and the pre-existing microflora. The second one is linked to innate immunity directly related to the genetic and/or immune predispositions of the individual: mutations affecting the CCR5 chemokine receptor, secretion of protective soluble factors, and particular HLA alleles. The third one is acquired immunity via the mechanisms of humoral and/or specific cellular immunity. These studies suggest anti HIV-1 vaccinal strategies aiming at a local immunization combining the different types of responses observed in these individuals.

HIV Infections↗

Positive end expiratory pressure and expiratory flow limitation: a model study.

Patients suffering from chronic obstructive pulmonary diseases, frequently exhibit expiratory airflow limitation. We propose a mathematical model describing the mechanical behavior of the ventilated respiratory system. This model has to simulate applied positive end-expiratory pressure (PEEP) effects during expiration, a process used by clinicians to improve airflow. The proposed model consists of a nonlinear two-compartment system. One of the compartments represents the collapsible airways and mimics its dynamic compression, the other represents the lung and chest wall compartment. For all clinical conditions tested (n=16), the mathematical model simulates the removal of expiratory airflow limitation at PEEP lower than 70-80% of intrinsic end-expiratory pressure (PEEPi), i.e. the end-expiratory alveolar pressure (PAet) without PEEP. It also shows the presence of an optimal PEEP. The optimal PEEP contributes to decrease PAet from 7.4+/-0.9 (SD) to 5.4+/-0.9 hPa (p < 0.0001; mild flow limitation) and from 11.8+/-1.1 to 7.8+/-0.7 hPa (p < 0.0001; severe flow limitation). Resistance of the collapsible compartment is decreased from 53+/-7 to 8.2+/-5.9 hPa.L(-1).s (p < 0.0001; mild flow limitation) and from 80+/-11 to 6.9+/-5.4 hPa.L(-1).s (p < 0.0001; severe flow limitation). This simplistic mathematical model gives a plausible explanation of the expiratory airflow limitation removal with PEEP and a rationale to the practice of PEEP application to airflow limited patients.

Airway Resistance↗

Highly sensitive and rapid detection of antibody catalysis by luminescent bacteria.

A highly sensitive, inexpensive, and facile bioluminescent assay for the detection of catalytic antibodies has been developed. This assay may be used for the early detection of antibody catalysis. The efficiency of this technique was exemplified by the use of the luminescent bacterium VhM42 for monitoring an antibody-catalyzed retroaldol fragmentation reaction with aldolase antibodies 38C2 and 24H6.

Aldehydes↗

Heterogeneity of angiogenesis and blood vessel maturation in human tumors: implications for antiangiogenic tumor therapies.

Microvessel density (MVD) counting techniques have been widely used to assess the vasculature in tumors. MVD counts assess the presence of blood vessels but do not give an indication of the degree of angiogenesis and the functional status of the tumor neovasculature. To analyze angiogenesis and the functional status of the tumor vascular bed, we have quantitated endothelial cell proliferation and the recruitment of pericytes in human tumors [glioblastomas (n = 30), renal cell carcinomas (n = 22), colon carcinomas (n = 18), mammary carcinomas (n = 24), lung carcinomas (n = 15), and prostate carcinomas (n = 19)]. These findings were compared to the physiological angiogenesis in the cyclic bovine ovarian corpus luteum. Tissue sections were examined applying double-labeling immunohistochemical techniques to detect proliferating endothelial cells and to colocalize endothelial cells and pericytes. The following parameters were quantitated: (a) MVD count; (b) proliferating capillary index (PCI); (c) proliferating tumor versus endothelial cell index; and (d) microvessel pericyte coverage index (MPI). Based on endothelial cell proliferation, angiogenesis was found to be present in all tumors with characteristic and significant differences between the tumor types (glioblastomas, PCI = 9.6 +/- 6.1%; renal cell carcinomas, PCI = 9.4 +/- 5.2%; colon carcinomas, PCI = 7.8 +/- 5.2%; mammary carcinomas, PCI = 5.0 +/- 4.8%; lung carcinomas, PCI = 2.6 +/- 2.5%; prostate carcinomas, PCI = 2.0 +/- 1.4%). There was a considerable degree of heterogeneity in the intensity of angiogenesis within each tumor group, as indicated by large standard deviations. Even in the most angiogenic tumors, angiogenesis was found to be 4 to 20 times less intense as compared with the physiological angiogenesis in the growing ovarian corpus rubrum (PCI = 40.6 +/- 6.2%). Varying degrees of pericyte recruitment to the tumor microvasculature were determined in the different tumor types (glioblastomas, MPI = 12.7 +/- 7.9%; renal cell carcinomas, MPI = 17.9 +/- 7.8%; colon carcinomas, MPI = 65.4 +/- 10.5%; mammary carcinomas, MPI = 67.3 +/- 14.2%; lung carcinomas, MPI = 40.8 +/- 14.5%; prostate carcinomas, MPI = 29.6 +/- 9.5%). The data demonstrate distinct quantitative variations in the intensity of angiogenesis in malignant human tumors. Furthermore, the varying degrees of pericyte recruitment indicate differences in the functional status of the tumor vasculature in different tumors that may reflect varying degrees of maturation of the tumor vascular bed.

Animals↗

[Clinical evaluation of alarm efficieny in intensive care].

OBJECTIVE: To evaluate the efficiency of haemodynamic and respiratory monitoring system by a clinical analysis of the alarms. STUDY DESIGN: Observational prospective study. PATIENTS: 25 patients who presented acute respiratory distress syndrome and who were monitored with haemodynamic and respiratory monitoring. METHODS: Each minute, a bedside clinical observer analysed alarms from the monitoring according to detection or absence to clinical events. Four situations were defined to statistical descriptive analysis: a) false positive (FP); b) true positive (TP); c) false negative (FN); and d) true negative (TN). True positive alarm which induced consequences on patients care were also analysed. RESULTS: 15,013 minutes allowed the recordings of 3,665 alarms, 44% from arterial pressure, 17% from SpO2 and 12% from airways maximal pressure. 46% were false positive alarms inducing a noisy pollution. The positive predictive value PPV = TP/(TP + FP) of these alarms were respectively 51% for arterial pressure, 18% for SpO2 and 100% for Paw. Only 5% of true positive alarms induced consequences on patients care. CONCLUSION: This protocol allowed the evaluation of monitoring efficiency. This kind of evaluation may help to improve monitoring capacity with reducing noisy pollution from false positive alarms.

Adolescent↗

Time-dependent pressure distortion in a catheter-transducer system: correction by fast flush.

BACKGROUND: Distortion of the pressure wave by a liquid-filled catheter-transducer system leads most often to an overestimation in systolic arterial blood pressure in pulmonary and systemic circulations. The pressure distortion depends on the catheter-transducer frequency response. Many monitoring systems use either mechanical or electronic filters to reduce this distortion. Such filters assume, however, that the catheter-transducer frequency response does not change over time. The current study aimed to study the changes with time of the catheter-transducer frequency response and design a flush procedure to reverse these changes back to baseline. METHODS: An in vitro setup was devised to assess the catheter-transducer frequency response in conditions approximating some of those met in a clinical environment (slow flushing, 37 degrees C, 48-h test). Several flush protocols were assessed. RESULTS: Within 48 h, catheter-transducer natural frequency decreased from 17.89 +/- 0.36 (mean +/- SD) to 7.35 +/- 0.25 Hz, and the catheter-transducer damping coefficient increased from 0.234 +/- 0.004 to 0.356 +/- 0.010. Slow and rapid flushing by the flush device built into the pressure transducer did not correct these changes, which were reversed only by manual fast flush of the transducer and of the catheter. These changes and parallel changes in catheter-transducer compliance may be explained by bubbles inside the catheter-transducer. CONCLUSIONS: Catheter-transducer-induced blood pressure distortion changes with time. This change may be reversed by a manual fast flush or "rocket flush" procedure, allowing a con. stant correction by a filter.

Anesthesiology↗

Cardiorespiratory interactions during resistive load breathing.

The addition to the respiratory system of a resistive load results in breathing pattern changes and in negative intrathoracic pressure increases. The aim of this study was to use resistive load breathing as a stimulus to the cardiorespiratory interaction and to examine the extent of the changes in heart rate variability (HRV) and respiratory sinus arrhythmia (RSA) in relation to the breathing pattern changes. HRV and RSA were studied in seven healthy subjects where four resistive loads were applied in a random order during the breath and 8-min recording made in each condition. The HRV spectral power components were computed from the R-R interval sequences, and the RSA amplitude and phase were computed from the sinusoid fitting the instantaneous heart rate within each breath. Adding resistive loads resulted in 1) increasing respiratory period, 2) unchanging heart rate, and 3) increasing HRV and changing RSA characteristics. HRV and RSA characteristics are linearly correlated to the respiratory period. These modifications appear to be linked to load-induced changes in the respiratory period in each individual, because HRV and RSA characteristics are similar at a respiratory period obtained either by loading or by imposed frequency breathing. The present results are discussed with regard to the importance of the breathing cycle duration in these cardiorespiratory interactions, suggesting that these interactions may depend on the time necessary for activation and dissipation of neurotransmitters involved in RSA.

Adult↗

The phenolic vir gene inducer ferulic acid is O-demethylated by the VirH2 protein of an Agrobacterium tumefaciens Ti plasmid.

Some or possibly all Ti plasmids of Agrobacterium tumefaciens encode a bicistronic operon designated virH, which encodes two proteins, VirH1 and VirH2, that resemble a family of cytochrome P450-type monooxygenases. Expression of this operon is induced by a family of phenolic compounds that induce all other operons within the vir regulon. We hypothesized that either or both of these proteins might metabolize some or all of these phenolic compounds. We therefore tested induction of a vir promoter by a variety of phenolic compounds in isogenic strains that express or lack virH1 and virH2. Although some compounds were equally effective inducers regardless of the virH status, other compounds induced vir expression far more effectively in the virH mutant than in the virH-proficient host. For all tested compounds, VirH2 appeared to be solely responsible for this effect. One such compound, ferulic acid, was chosen for biochemical analysis. Ferulic acid was degraded by a VirH-proficient host but not by a VirH mutant. The wild-type strain released large amounts of a more hydrophilic compound into the cell supernatant. This compound was tested by mass spectroscopy, nuclear magnetic resonance and UV spectroscopy and found to consist of caffeic acid. This indicates that wild-type strains convert virtually all added ferulic acid to caffeic acid, and that VirH2 is essential for this O-demethylation reaction. Ferulic acid was far more toxic than caffeic acid to the wild-type strain, although the wild-type strain was more resistant to ferulic acid than was the virH mutant. Caffeic acid was slowly removed from the broth, suggesting further metabolic reactions.

Agrobacterium tumefaciens↗

New statistical method for detection and quantification of respiratory sinus arrhythmia.

A statistical method with the advantages of 1) enabling graphical representation of within-respiratory cycle heart rate variations, 2) detecting the presence of respiratory sinus arrhythmia (RSA) in a moving window, and 3) providing breath-by-breath RSA amplitude and phase obtained from the fitting of a sinusoid to the instantaneous relative heart rate is presented.

Adolescent↗

Effects of resistive loading on the pattern of breathing.

In order to determine changes in breathing patterns brought about by resistive loading, ventilation was recorded in 11 healthy subjects with four linear resistances (3.57, 5.75, 8.76 and 13.13 cmH2O L(-1) sec) added in a random order throughout the entire breath. At steady state, a breath-by-breath analysis of airflow was used to quantify the pattern of breathing in terms of respiratory variables: TI, TE, Tt, VT, VT/TI, TI/Tt, and by taking TI, TE, VT all together (TRIAD) and also the shape of the entire airflow profile quantified by harmonic analysis (ASTER). Group analysis using ANOVA showed significant changes in all variables. There were increasing changes with increasing loads in all variables, the smallest changes being in TI/Tt. Within to between-individual comparisons between two loads showed that only TI/Tt and the ASTER were more similar within than between-individuals for all comparisons. It was concluded that at steady state mechanisms of load compensation come into play inducing changes in the pattern of breathing proportional to the loads while maintaining some of the individual characteristics.

Adaptation, Physiological↗

Respiratory mechanics during laparoscopic cholecystectomy: the effects of the abdominal wall lift.

UNLABELLED: The abdominal wall lift (AWL) has been proposed for laparoscopic cholecystectomy to reduce hemodynamic effects caused by carbon dioxide (CO2) and high intraabdominal pressures (IAP). Data concerning effects of AWL on respiratory mechanics are scant. We therefore used a noninvasive method to evaluate whether the AWL could offset these effects. The PETCO2, airflow, and airway pressure were continuously measured in nine patients undergoing laparoscopic cholecystectomy using an AWL with minimal CO2 insufflation. We used a least-squares method to calculate maximal airway pressure (Pmax), elastance (Ers), and resistances (Rrs) of the respiratory system. After CO2 insufflation, the initiation of AWL resulted in a significantly decreased IAP (from 13 to 6 mm Hg; P < 0.001) and Rrs (from 20.6 to 17.8 cm H2O.L(-1).s(-1); P = 0.029), whereas Ers was partly modified (34.0 to 33.3 cm H2O/L; not significantly different). With AWL, we hypothesized that the diaphragm remained flat and stiff, outweighing the beneficial effect of the decrease of IAP on Ers. PETCO2 significantly increased after AWL and at the end of the procedure. We conclude that AWL partly reverses the impairment of the respiratory mechanics induced by CO2 insufflation during laparoscopic surgery. IMPLICATIONS: The abdominal wall lift (AWL), acting on the abdominal chest wall, had some benefits during laparoscopic surgery by limiting CO2 peritoneal insufflation and several side effects, such as hemodynamics. We examined the consequences of this technique on respiratory mechanics in nine patients undergoing laparoscopic cholecystectomy. Our findings suggest that the AWL decreases intraabdominal pressure and respiratory resistances without a significant effect on respiratory elastance.

Abdomen↗

Analogs of the autoinducer 3-oxooctanoyl-homoserine lactone strongly inhibit activity of the TraR protein of Agrobacterium tumefaciens.

The TraR and TraI proteins of Agrobacterium tumefaciens mediate cell-density-dependent expression of the Ti plasmid tra regulon. TraI synthesizes the autoinducer pheromone N-(3-oxooctanoyl)-L-homoserine lactone (3-oxo-C8-HSL), while TraR is an 3-oxo-C8-HSL-responsive transcriptional activator. We have compared the abilities of 3-oxo-C8-HSL and 32 related compounds to activate expression of a TraR-regulated promoter. In a strain that expresses wild-type levels of TraR, only 3-oxo-C8-HSL was strongly stimulatory, four compounds were detectably active only at high concentrations, and the remaining 28 compounds were inactive. Furthermore, many of these compounds were potent antagonists. In contrast, almost all of these compounds were stimulatory in a congenic strain that overexpresses TraR and no compound was a potent antagonist. We propose a model in which autoinducers enhance the affinity of TraR either for other TraR monomers or for DNA binding sites and that overexpression of TraR potentiates this interaction by mass action. Wild-type A. tumefaciens released a rather broad spectrum of autoinducers, including several that antagonize induction of a wild-type strain. However, under all conditions tested, 3-oxo-C8-HSL was more abundant than any other analog, indicating that other released autoinducers do not interfere with tra gene induction. We conclude that (i) in wild-type strains, only 3-oxo-C8-HSL significantly stimulates tra gene expression, while many autoinducer analogs are potent antagonists; (ii) TraR overexpression increases agonistic activity of autoinducer analogs, allowing sensitive biodetection of many autoinducers; and (iii) autoinducer stimulatory activity is potentiated by TraR overproduction, suggesting that autoinducers may shift an equilibrium between TraR monomers and dimers or oligomers. When autoinducer specificities of other quorum-sensing proteins are tested, care should be taken not to overexpress those proteins.

Agrobacterium tumefaciens↗

[Correction to the airflow measurement in the presence of a leak between the trachea and endotracheal tube].

PURPOSE: To estimate the leak between the endotracheal tube and the trachea in newborns in order to compensate for errors in airflow measurement and to monitor mechanical variables from pressure and flow signals. METHODS: Assuming that the leak resistance (Rf) is constant during a respiratory cycle, the resistive properties of the endotracheal tube were evaluated. The method was validated in the intensive care unit with a mechanical test lung and assessed on recordings of three newborns during mechanical ventilation for RDS. We have used a least squares method for the estimation of positive end expiratory pressure (PEEP) on both newborns and simulated data. RESULTS: Direct measurements of simulated leak resistances on the mechanical lung are in agreement with our estimation of leak resistances. In newborns, the success of flow correction is evidenced on end inspiratory pauses: corrected flow drops to zero while raw data show a constant nonzero flow. On the simulated lung, the PEEP underestimation with uncorrected flow ranges from 10 to 20 cm H20 while the corresponding, underestimation with corrected flow is less than 2 cm H2O. In newborns, the flow correction shifts the estimated PEEP from negative values (-0.3 +/- 1.3 cm H2O before correction) to positive values (3.6 +/- 0.7 cm H2O after correction) higher than the imposed PEEP (2 cm H2O). CONCLUSIONS: The efficiency of this simple method has been demonstrated. It could be used successfully on adult patients, as there will not be flow correction in the absence of leaks.

Humans↗

Evaluation of respiratory inductive plethysmography: accuracy for analysis of respiratory waveforms.

OBJECTIVE: To assess the accuracy of respiratory inductive plethysmography (RIP) waveforms to those obtained with whole body plethysmograph (BP) as this device gives a plethysmographic signal and a pneumotachograph (PNT). DESIGN: Randomized controlled trial. SETTING: Physiologic laboratory in a university hospital. PARTICIPANTS: Eleven subjects from the laboratory staff. INTERVENTIONS: This study was achieved during four consecutive periods in subjects breathing spontaneously and through different added resistive loads. Using the least square method calibration, two RIP waveforms, VRIP.BP(t) and VRIP.PNT(t), were simultaneously calculated with coefficients obtained from BP and from PNT volume waveforms, respectively VBP(t) and VPNT(t). For each recording, to compare volume waveforms, we calculated their differences in term of distances, DRIP-BP and DRIP-PNT, between the normalized RIP volume signal (respectively, VRIP.BP[t] and VRIP.PNT[t]) and its normalized reference (respectively, VBP[t] and VPNT[t]). We also calculated the distance DPNT-BP between the two normalized references VBP(t) and VPNT(t). RESULTS: No significant effect of load or time on the distance occurred. Including all the recordings, the mean distance DRIP-BP (3.4+/-1.1%) appears significantly lower than both the mean distance DRIP-PNT (4.5+/-1.3%; p<0.04) and the mean distance DPNT-BP (4.6+/-0.9%; p<0.008). For each period or load level, DRIP-BP appears to be lower than DRIP-PNT and DPNT-BP. CONCLUSION: The RIP seems reasonably accurate for analysis of respiratory waveform while subjects subsequently breathe against resistive loads.

Adult↗

Enzymatic synthesis of a quorum-sensing autoinducer through use of defined substrates.

Many bacteria, including several pathogens of plants and humans, use a pheromone called an autoinducer to regulate gene expression in a cell density-dependent manner. Agrobacterium autoinducer [AAI, N-(3-oxo-octanoyl)-L-homoserine lactone] of A. tumefaciens is synthesized by the Tral protein, which is encoded by the tumor-inducing plasmid. Purified hexahistidinyl-Tral (H6-Tral) used S-adenosylmethionine to make the homoserine lactone moiety of AAI, but did not use related compounds. H6-Tral used 3-oxo-octanoyl-acyl carrier protein to make the 3-oxo-octanoyl moiety of AAI, but did not use 3-oxo-octanoyl-coenzyme A. These results demonstrate the enzymatic synthesis of an autoinducer through the use of purified substrates.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗