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Biomedical subjects

R Everett

Publications and source records attributed to R Everett.

At least 19 recordsLinked to original sources
PubMed2005

Human papillomavirus 16 L2 inhibits the transcriptional activation function, but not the DNA replication function, of HPV-16 E2.

In this study we analysed the outcome of the interaction between HPV-16 L2 and E2 on the transactivation and DNA replication functions of E2. When E2 was expressed on its own, it transactivated a number of E2-responsive promoters but co-expression of L2 led to the down-regulation of the transcription transactivation activity of the E2 protein. This repression is not mediated by an increased degradation of the E2 protein. In contrast, the expression of L2 had no effect on the ability of E2 to activate DNA replication in association with the viral replication factor E1. Deletion mutagenesis identified L2 domains responsible for binding to E2 (first 50 N-terminus amino acid residues) and down-regulating its transactivation function (residues 301-400). The results demonstrate that L2 selectively inhibits the transcriptional activation property of E2 and that there is a direct interaction between the two proteins, although this is not sufficient to mediate the transcriptional repression. The consequences of the L2-E2 interaction for the viral life cycle are discussed.

Capsid Proteins↗
PubMed2001

Inductance plethysmography: an alternative signal to servocontrol the airway pressure during proportional assist ventilation in small animals.

During proportional assist ventilation (PAV), the ventilator pressure is servocontrolled throughout each spontaneous inspiration such that it instantaneously increases in proportion to the airflow (resistive unloading mode), or inspired volume (elastic unloading mode), or both (combined unloading mode). The PAV pressure changes are generated in a closed-loop feedback circuitry commonly using a pneumotachographic signal. In neonates, however, a pneumotachograph increases dead space ventilation, and its signal may include a substantial endotracheal tube leak component. We hypothesized that respiratory inductive plethysmography (RIP) can replace pneumotachography to drive the ventilator during PAV without untoward effects on ventilation or respiratory gas exchange. Ten piglets and five rabbits were supported for 10-min (normal lungs) or 20-min (meconium injured lungs) periods by each of the three PAV modes. In each mode, three test periods were applied in random order with the ventilator driven by the pneumotachograph signal, or the RIP abdominal band signal, or the RIP sum signal of rib cage and abdomen. Interchanging the three input signals did not affect the regularity of spontaneous breathing, and gas exchange was achieved with similar peak and mean airway pressures (ANOVA). However, the RIP sum signal worked adequately only when the relative gains of rib cage and abdominal band signal were calibrated. We conclude that an RIP abdominal band signal can be used to generate PAV, avoiding increased dead space and endotracheal tube leak problems.

Airway Resistance↗
PubMed2001

Proportional assist ventilation decreases thoracoabdominal asynchrony and chest wall distortion in preterm infants.

Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypothesized that application of positive airway pressure only during inspiration and in proportion to an infant's inspiratory effort should have a similar but more pronounced effect than CPAP alone. A ventilator providing airway pressure changes in proportion to flow and volume generated by an infant (proportional assist ventilation) was used to unload the respiratory pump during inspiration. Ten preterm infants were studied [birth weight, 745 (635-1175) g; gestational age, 26.5 (24-31) wk; postnatal age 3 (1-7) d; medium (range)]. TAA and CWD were determined by respiratory inductive plethysmography. TAA was expressed as the phase angle between the rib cage and abdominal motion and CWD as the total compartmental displacement ratio. In addition, we measured tidal volume with a pneumotachograph and esophageal and airway pressure deflections with pressure transducers. Measurements were obtained during alternating periods of CPAP and two different degrees of support (Gain 1 = 1.09 +/- 0.68, Gain 2 = 1.84 +/- 0.84 cm H(2)O/mL) that were provided by a proportional assist ventilator. Phase angle and the total compartmental displacement ratio decreased with increasing gain compared with CPAP alone. Peak airway pressure increased from 0.6 to 3.8 to 7.6 cm H(2)O above positive end-expiratory pressure (PEEP) with CPAP, Gain 1, and Gain 2, respectively, as tidal volume increased from 2.8 to 4.1 to 4.7 mL/kg. Esophageal pressure changes decreased only little with increasing gain. Chest wall excursion increased and abdominal movement decreased, indicating a redistribution of tidal volume between chest and abdomen. We conclude that proportional assist ventilation reduces TAA and CWD by generating a small increase in airway pressure that occurs in synchrony and in proportion to each inspiratory effort.

Abdomen↗
PubMed2001

Closed-loop controlled inspired oxygen concentration for mechanically ventilated very low birth weight infants with frequent episodes of hypoxemia.

BACKGROUND: Mechanically ventilated very low birth weight infants often present with frequent episodes of hypoxemia, and maintaining arterial oxygen saturation by pulse oximetry (SpO(2)) within a normal range by manual fraction of inspired oxygen (FIO(2)) adjustments is difficult and time consuming. OBJECTIVES: An algorithm for closed-loop FIO(2) control (cFIO(2)) to maintain SpO(2) within a target range was compared with continuous manual FIO(2) (mFIO(2)) adjustments by a nurse in a group of ventilated infants who presented with frequent episodes of hypoxemia. RESULTS: Fourteen infants (birth weight: 712 +/- 142 g; gestational age: 25 +/- 1.6 weeks; age: 26 +/- 11 days; synchronized intermittent mandatory ventilation rate: 24 +/- 10 b/m; peak inspiratory pressure: 17.5 +/- 2.0 cmH(2)O; positive end-expiratory pressure: 4.3 +/- 0.5 cmH(2)O) were studied for 2 hours on each mode in random sequence. Both modes aimed to maintain SpO(2) between 88% and 96%. There were 15 +/- 7 and 16 +/- 6 hypoxemic episodes/hour (SpO(2) <88%, >5 s) during mFIO(2) and cFIO(2), respectively; episode duration was 41 +/- 23 and 32 +/- 15 s, totaling 19 +/- 16% and 17 +/- 12% of recording time. There were 13 +/- 10 and 10 +/- 8 hyperoxemic episodes/hour (SpO(2)>96%, >5 s) during mFIO(2) and cFIO(2,) respectively; episode duration was 27 +/- 15 and 24 +/- 19 s, totaling 15 +/- 14% and 10 +/- 9% of recording time. Mean SpO(2) and FIO(2) levels were similar during both modes. The nurse made 29 +/- 17 adjustments/hour during mFIO(2). There was a significant increase in the duration of normoxemia (SpO(2) between 88%-96%) during cFIO(2) (75 +/- 13 vs 66 +/- 14% of recording time). CONCLUSION: In this group of infants, cFIO(2) was at least as effective as a fully dedicated nurse in maintaining SpO(2) within the target range, and it may be more effective than a nurse working under routine conditions. We speculate that during long-term use, cFIO(2) may save nursing time and reduce the risks of morbidity associated with supplemental oxygen and episodes of hypo- and hyperoxemia.

Algorithms↗
PubMed1999

Proportional assist ventilation in low birth weight infants with acute respiratory disease: A comparison to assist/control and conventional mechanical ventilation.

OBJECTIVES: To compare the physiologic efficacy and safety aspects of proportional assist (PA), assist/control (A/C), and intermittent mandatory ventilation (IMV) in very low birth weight infants with acute respiratory illness and to test the hypothesis that ventilatory pressure requirements are lower and arterial oxygenation is improved during PA when compared with IMV or A/C at an equivalent inspired oxygen fraction. STUDY DESIGN: Randomized, 3-period, crossover design. METHODS: Thirty-six infants were stratified by birth weight (600 to 750, 751 to 900, and 901 to 1200 g) and exposed to consecutive 45-minute epochs of the 3 modalities in a sequence chosen at random. Tidal volumes of 4 to 6 mL/kg were targeted during A/C and IMV. The IMV rate was matched to the rate during an A/C test period. PA was adjusted to unload the resistance of the endotracheal tube and the disease-related increase in lung elastic recoil. RESULTS: Compared with A/C and IMV, PA maintained similar arterial oxygenation with lower airway and transpulmonary pressures (15% to 44% reduction depending on the index variable). The oxygenation index decreased by 28% during PA. No adverse events were observed. The number and severity of apneic episodes and periods of arterial oxygen desaturations were similar with the 3 modes. Similar results were obtained within each birth weight subgroup. CONCLUSIONS: PA safely maintains gas exchange with smaller transpulmonary pressure changes compared with A/C and IMV. It may therefore offer a way of reducing the incidence of chronic lung disease in low birth weight infants.

Acute Disease↗
PubMed1998

Disruption of the 5' and 3' splice sites flanking the major latency-associated transcripts of herpes simplex virus type 1: evidence for alternate splicing in lytic and latent infections.

The herpes simplex virus type 1 (HSV-1) latency-associated transcripts (LATs) are the only viral gene products expressed within latently infected neurones. The most abundant (major) LATs consist of two collinear nuclear polyA- RNAs of 2 kb and 1.5 kb which it has been suggested represent stable introns derived from a less abundant primary transcript (minor LAT). Consistent with this proposition is the identification of consensus splice donor and acceptor sites flanking major LATs which are conserved between HSV types 1 and 2. Here we test the functionality of the predicted splice sites within the context of the virus genome during productive infection in vitro and latent infection in vivo. To this end viruses in which the LAT splicing signals were disrupted by site-directed mutagenesis were constructed. We report that mutation of the splice acceptor site abrogates 2 kb major LAT generation during productive infection but does not significantly influence major LAT synthesis during neuronal latency. Similarly, mutation of the splice donor site significantly reduces levels of 2 kb major LAT during productive infection but has no detectable effect on the generation of 2 kb major LAT during neuronal latency as assessed by Northern and in situ hybridization analyses of latently infected neuronal tissue. From these data it can be concluded that the proposed splice sites flanking the major LAT region are dispensable for 2 kb major LAT production in neurones latently infected with HSV-1 but constitute functional splicing signals in productively infected non-neuronal cells.

Alternative Splicing↗
PubMed1998

Examination of determinants for intranuclear localization and transactivation within the RING finger of herpes simplex virus type 1 IE110k protein.

The herpesvirus regulatory protein IE110k possesses a cysteine-rich, RING finger motif required for its role in transactivation and virus replication. IE110k also localizes to subnuclear compartments termed PODs (PML oncogenic domains). Localization to PODs induces redistribution of the proteins associated with this nuclear compartment, including the cellular RING finger protein, PML. Here we construct a series of deletions, RING domain swaps and point mutations to analyse specific requirements within the IE110k RING finger for subnuclear localization, redistribution of PML and transactivation and we examine the relationship between these activities. We find that IE110k localizes to distinct nuclear subdomains that are more numerous than the cellular PODs and that mutation of two residues within a predicted loop of the RING finger, or replacing the IE110k RING finger with a RING finger from a cellular gene abrogates the ability of IE110k to localize to these extra compartments and traps IE110k in the original PODs. We further demonstrate that RING fingers from the cellular genes mdm-2 and Bmi I, when placed within IE110k, alter the nuclear distribution of IE110k, do not transactivate, and do not redistribute PML. We also demonstrate that the majority of wild-type IE110k, like PML, is associated with the nuclear matrix. Although substitutions and deletions within the RING finger abolish transactivation, these mutant proteins remain tightly associated with the matrix. These results further dissect the determinants involved in different aspects of nuclear compartmentalization of IE110k and are discussed in relation to PML, PODs and the IE110k RING finger.

Amino Acid Sequence↗
PubMed1998

A new method to analyze lung compliance when pressure-volume relationship is nonlinear.

Changes in dynamic lung compliance during inspiration and expiration cannot be modeled accurately with conventional algorithms. We developed a simple method to analyze pressure-volume (P/V) relationships under condition of nonlinearity (APVNL) and tested it in a lung model with known resistance and nonlinear P/V relationship. In addition, pulmonary mechanics in 22 infants, 11 of them with nonlinear P/V relationships, were analyzed with the new method. The findings were compared with those obtained by a recently introduced algorithm, multiple linear regression analysis (MLR) of the equation of motion. The APVNL method described the changing compliance (C) of the lung model accurately, whereas the MLR method underestimated C especially in the first half of the breath. In infants the MLR method gave highly variable, often nonphysiological C values in the beginning of a breath. In contrast, the coefficient of variability of measurements obtained by the APVNL method was significantly smaller (p < 0.02), and the indices of model-fit showed better agreement between calculated and observed pressure than for the MLR method (p < 0.02). We conclude that the APVNL method accurately describes nonlinear P/V relationships present during spontaneous breathing or mechanical ventilation. The method may be helpful in identifying and preventing pulmonary overdistention.

Airway Resistance↗
PubMed1998

Effects of respiratory mechanical unloading on thoracoabdominal motion in meconium-injured piglets and rabbits.

Impaired pulmonary mechanics can cause chest wall distortion (CWD) so that work of breathing is dissipated in deforming the rib cage. We hypothesized that respiratory mechanical unloading as a technique of assisted mechanical ventilation would reduce CWD in animals with injured lungs. We studied five piglets and five adult rabbits to test across different ages and chest configurations. As a result of intratracheal meconium instillation, lung compliance decreased from 21 (median; range 17-35) to 9.5 (6.7-14) mL/kPa/kg in rabbits and from 26 (18-31) to 7.9 (4.9-11) in piglets. Airway resistance increased from 5.0 (4.6-6.1) to 6.9 (5.8-7.9) kPa/L/s in rabbits only. Respiratory inductive plethysmography was used to measure the phase shift between the rib cage and abdominal compartment movements and the total compartmental displacement ratio. We aimed at unloading at least three-fourths of lung elastance in all animals and 2.0 kPa/L/s of resistance in rabbits. Elastic unloading decreased the phase shift in all but one animal. It reduced the total compartmental displacement ratio from 1.27 (1.14-3.73) to 1.16 (1.02-1.82) in piglets and from 1.77 (1.45-5.24) to 1.37 (1.11-4.78) in rabbits. The inspiratory rib cage expansion increased, whereas abdominal expansion did not. The tidal esophageal pressure deflection decreased. Tidal volume increased, whereas respiratory rate remained unaffected so that the partial pressure of arterial CO2 decreased. Resistive unloading as an adjunct to elastic unloading further reduced CWD and induced a more rapid, shallower breathing. We conclude that respiratory unloading as a mechanical support to spontaneous breathing reduces CWD. We speculate that the decrease in CWD increases ventilatory efficiency for a given diaphragmatic effort.

Abdomen↗
PubMed1997

Increased incidence of sighs (augmented inspiratory efforts) during synchronized intermittent mandatory ventilation (SIMV) in preterm neonates.

A reflex resulting in a deep, sigh-like inspiratory effort (augmented breath) is frequently triggered during synchronized mechanical ventilation in preterm infants. We studied the incidence of augmented inspiratory efforts and their effect on ventilation and lung compliance during conventional IMV and synchronized IMV (SIMV) in 15 preterm neonates (GA 26.7 +/- 1.5 wks (mean +/- SD), BW 925 +/- 222 g, age 1-8 days). Augmentation of spontaneous inspiratory effort was defined as an esophageal pressure deflection occurring coincident with a synchronized mechanical breath and exceeding the previous unassisted spontaneous effort by more than 50%. The incidence of augmented breaths was higher during SIMV (11.1 +/- 7.7%; P < 0.01) than during conventional IMV (5.1 +/- 6.1%). However, when the synchronized breaths were triggered late (200-300 msec) after the onset of inspiration, augmented breaths occurred no more frequently than during conventional IMV (6.0 +/- 4.7%). The incidence of augmented breaths correlated inversely with dynamic lung compliance (P = 0.014), but was not significantly influenced by a change in PEEP. Although inspiratory effort increased nearly three times during the augmented breaths, tidal volume increased only 12%. The change in tidal volume was limited because the augmented effort reached its maximal negativity only approximately 500 ms after the beginning of the synchronized, mechanical breath and at a time when the mechanical breath had already ended. For this reason the augmented effort did not contribute significantly to minute ventilation, but only prolonged inspiration. Dynamic lung compliance did not change significantly after an augmented breath. The results indicate that augmented inspiratory efforts are more common in preterm neonates ventilated with SIMV than with conventional IMV, but do not contribute significantly to ventilation.

Cohort Studies↗
PubMed1997

Computer-controlled minute ventilation in preterm infants undergoing mechanical ventilation.

INTRODUCTION: Computer-controlled minute ventilation (CCMV) continuously adjusts the ventilator rate to changes in spontaneous respiratory drive and pulmonary mechanics to maintain a preset total minute ventilation. HYPOTHESIS: We hypothesized that CCMV would maintain ventilation and oxygenation with fewer mechanical breaths than conventional intermittent mandatory ventilation in very low birth weight infants. METHODS: Very low birth weight infants in clinically stable condition who were undergoing mechanical ventilation were enrolled. The number of mechanical breaths, total and mechanical expiratory minute ventilation, mean airway pressure, oxygen hemoglobin saturation by pulse oximetry, and transcutaneous partial carbon dioxide and partial oxygen tensions were obtained during intermittent mandatory ventilation and CCMV (45 to 60 minutes) and compared by paired t test. RESULTS: Fifteen infants were studied. Birth weight (median, range) was 700 gm (550 to 1205 gm), gestational age 26 weeks (23 to 34 weeks), age 21 days (3 to 50 days). When switched from intermittent mandatory ventilation to CCMV, the number of mechanical breaths was reduced (15 +/- 2.8 to 8.6 +/- 2.9 breaths per minute, p < 0.001), leading to lower airway pressure (3.97 +/- 1.00 to 3.45 +/- 1.00 cm H2O, p < 0.001) and lower expiratory minute ventilation generated by the mechanical ventilator (116 +/- 31 to 65 +/- 28 ml/min per kilogram, p < 0.001), while total expiratory minute ventilation remained unchanged. Mean transcutaneous partial carbon dioxide and oxygen tensions, oxygen hemoglobin saturation, and the time spent within different oxygen hemoglobin saturation ranges did not differ between both ventilatory modes. CONCLUSION: CCMV maintained adequate ventilation and oxygenation with lower mechanical ventilatory support than IMV. CCMV may reduce barotrauma and chronic lung disease during long-term use.

Down-Regulation↗
PubMed1997

Efficacy of imidacloprid for removal and control of fleas (Ctenocephalides felis) on dogs.

OBJECTIVE: To evaluate efficacy of a 9.1% (w/w) imidacloprid solution, applied topically, to remove fleas from dogs and the duration of residual flea control when dogs were exposed to continuing flea infestation. ANIMALS: 32 adult mixed-breed dogs. PROCEDURE: Dogs were allocated to 4 groups of 8 dogs each; dogs of 3 groups received a single dose of imidacloprid, and those of the fourth group received excipient. Each dog was infested with 100 adult fleas on study days -3, -1, 6, 13, 20, 27, and 33. Treatments were applied on day 0. Each dog was examined for live fleas on days -2, 1, 7, 14, 21, 28, and 34. Posttreatment efficacy was determined by comparing the mean number of live fleas remaining on the treated dogs with the mean number of live fleas remaining on the control dogs. RESULTS: All 3 imidacloprid dosages provided flea control > or = 96.9% one day after treatment. Maximal efficacy of all 3 dosages (99.1 to 100%) was observed at 7 days after treatment. Flea control with 3.75 mg of imidacloprid/kg of body weight ranged from 94.4 to 96.9% for days 14 to 28 and decreased to 91.6% by 34 days after treatment. Flea control with 7.5 and 10.0 mg of imidacloprid/kg was 97.8 to 100% through day 28. At day 34, dosages of 7.5 and 10.0 mg of imidacloprid/kg were 97.6 and 96.9% efficacious, respectively. CONCLUSION: 7.5 or 10.0 mg of imidacloprid/kg are equivalent and superior to 3.75 mg/kg for flea control over the course of a 34 day posttreatment period. CLINICAL RELEVANCE: Monthly imidacloprid application of 7.5 to 10 mg/kg will rapidly kill existing and reinfesting flea infestations on dogs and break the flea life cycle by killing adult fleas before egg production begins.

Administration, Topical↗
PubMed1996

Intrasubject variability of repeated pulmonary function measurements in preterm ventilated infants.

This study set out to describe the variability and assess the reproducibility of repeated pulmonary function measurements in ventilated preterm infants. We measured tidal volume (VT), lung compliance (CL), and resistance (RL) in 16 infants (mean +/- SD: birthweight 1222 +/- 343 g) during spontaneous breathing and during mechanical ventilation, suppressing breathing efforts by mild hyperventilation. CL and RL were calculated from the equation of motion using linear regression analysis (LR), and by the Mead and Wittenberger method (MW). Flow and transpulmonary pressure were recorded for at least two consecutive periods, after which the esophageal tube was removed and replaced 1 hour later for a second set of recordings. The mean percent change (% delta) between the initial and the repeated measurements with their respective 95% confidence intervals were calculated. Reproducibility was assessed by the intraclass correlation coefficient (ICC) (total agreement = 1, good reproducibility > or = 0.75). The mean % delta between initial and repeat measurements during spontaneous breathing ranged from 11% to 14% for CL and VT, and from 22% to 32% for RL. The variation for RL was even higher when the analysis was done separately for the inspiratory and expiratory phase. CL and VT had good reproducibility (ICC > 0.9), while RL was significantly less reproducible (ICC < 0.75). Measurements obtained from mechanical breaths had less variability than from spontaneous breaths, ranging from 8% to 15% for CL and VT, and from 13% to 21% for RL. Reproducibility assessed by the ICC was good for most measurements during mechanical breaths. The variability and reproducibility of measurements were similar for both methods of analysis during mechanical ventilation, but during spontaneous breathing variability was larger with the MW method than with LR analysis. We concluded that VT and CL were reproducible during spontaneous and mechanical breathing. However, RL measurements were reproducible only during mechanical ventilation. The high variability of RL in spontaneously breathing preterm infants may reduce the clinical usefulness of this measurement for individual patients.

Humans↗
PubMed1996

Patient-triggered ventilation: a comparison of tidal volume and chestwall and abdominal motion as trigger signals.

Patient-triggered synchronized ventilation requires reliable and early detection of the infant's inspiratory effort. Several trigger methods have been developed that frequently lack the sensitivity to detect inspiration in small preterm infants (trigger failure), or show a high rate of breaths triggered by artifacts in the respiratory signal (autotrigger). The purpose of this study was to determine the effectiveness of the following trigger signals: abdominal movement sensed by a newly developed induction technique, chestwall motion detected by changes in transthoracic impedance, and tidal volume measured by anemometry at the endotracheal tube connector. Ten preterm infants (birth weight, 580-1,424 g; median weight, 943 g; study weight, 535-1,415 g; median weight, 838 g; gestation age, 26-32 weeks, median gestational age, 28 weeks, study age, 1-50 days, median study age, 11 days) were included in the study. A Sechrist SAVI ventilator was triggered by one of three signals: chestwall or abdominal movement, or tidal volume generated by the infants. Response time between beginning of inspiratory flow, the occurrence of the trigger signal (signal delay), and the onset of the triggered breath (trigger delay) were determined for each of the three signals. The signal response time was -13.5 msec (95% CI, -33 to -2 msec) for the abdominal movement signal, indicating that it started before inspiratory flow; 0.0 msec for the volume signal; and 44.0 msec (95% CI, 29-73 msec) for the chestwall signal (P < 0.002); this long delay was secondary to chestwall distortion and a subsequent delay in outward ribcage movement in many infants. The trigger delay for the abdominal signal was 90.0 msec (95% CI, 55-104 msec), 135.5 msec (95% CI: 82-186 msec) for the volume signal, and 176.5 msec (95% CI: 165-232 msec) for the chestwall signal, indicating that there was a difference in the rise time of signal voltage between the three methods (P < 0.01). The rate of autotriggered breaths was 3.2% (95% CI, 0.3-9.3%) when using the abdominal signal, 0.55% (95% CI, 0.0-2.1%) for the tidal volume signal, and 11.25% (95% CI, 0.5-27.8%) for the chestwall signal (P < 0.05). The incidence of trigger failure was low with all three signals and was not significantly different between the techniques. In summary, the chestwall signal had a long trigger delay and was highly susceptible to false triggering. It is, therefore, not a reliable trigger signal for synchronized mechanical ventilation in preterm infants. In contrast, tidal volume and abdominal movement signals had an acceptable trigger delay and a low rate of autotriggering, making them useful clinical trigger signals.

Confidence Intervals↗
PubMed1996

Influence of different methods of synchronized mechanical ventilation on ventilation, gas exchange, patient effort, and blood pressure fluctuations in premature neonates.

We studied the effects of two methods of synchronized mechanical ventilation [synchronized intermittent mandatory ventilation (SIMV) and assist/control (A/C)] on ventilation, gas exchange, patient effort, and arterial blood pressure (ABP) fluctuations. SIMV and A/C were applied in random order in 12 preterm neonates (gestational age, 29.7 +/- 2.3 weeks; birth weight, 1,217 +/- 402 g). We measured total (Vetot) and mechanical (Vemech) minute ventilation, spontaneous (Vtspont) and ventilator supported (Vtmech) tidal volume, transcutaneous oxygen saturation (SpO2), transcutaneous PO2 (TcPO2), and PCO2, (TcPCO2), mean airway pressure (Paw), phasic esophageal pressure deflections (Pe) as an estimate of inspiratory effort, mean arterial blood pressure (ABP), and beat-to-beat ABP fluctuations. The measurements obtained during conventional intermittent mandatory ventilation (IMV) were compared with the recordings during SIMV and A/C. To make the measurement conditions comparable and to prevent hyperventilation, peak inspiratory pressure was reduced during the A/C mode so that Vetot remained in the same range as during the IMV mode. Whereas Vetot was similar in all three conditions by study design, Vemech was larger during SIMV and A/C than during IMV. Vtmech increased during SIMV and by study design was smaller during A/C than during IMV. Pe decreased during SIMV and A/C compared with IMV, and Paw was higher during A/C than during IMV or SIMV. Beat-to-beat ABP fluctuations were reduced during SIMV and A/C compared with IMV and showed a close positive correlation with Pe changes. We conclude that SIMV increases Vemech and reduces Pe compared with IMV, resulting in smaller intrathoracic and ABP fluctuations. During A/C, a substantial portion of the spontaneous respiratory effort is shifted to the ventilator, resulting in a further decrease in Pe and ABP fluctuations.

Blood Pressure↗
PubMed1996

Patient-triggered ventilation in neonates: comparison of a flow-and an impedance-triggered system.

We conducted a study with the objective of comparing the performance of two different systems for patient-triggered ventilation in neonates (impedance versus flow/volume-triggered) by measuring response time, autotrigger and trigger failure rates, ventilation, and gas exchange. The two ventilator systems were applied in random order in 10 preterm neonates (median gestational age: 30.5 wk; range: 27 to 34 wk; body weight: 1,266 g; range: 840 to 2,240 g) using identical ventilator settings. The median (range) response time was 169 (98 to 305) ms for the impedance system and 115 (79 to 184) ms for the flow/volume system (p < 0.01). The longer and more variable response time of the impedance system was secondary to a phase lag of the impedance signal caused by chest wall distortion. Although 13.1 (0.2 to 29.4)% of mechanical breaths were autotriggered with the impedance system, there were no autotriggered breaths using the flow/volume system (p < 0.01). The rate of trigger failures was not significantly different with the two systems, at 1.2 (0 to 4.4)% (impedance) versus 3.1 (0 to 6.4)% (flow/volume). Minute ventilation was smaller with the impedance system (p < 0.001), because of the larger number of breaths triggered late in inspiration or during expiration. We conclude that the flow/volume-triggered system is less prone to autotriggering and has a shorter and more consistent response time than the impedance-triggered system. The impedance-triggered system is more susceptible to artifacts and chest wall distortion.

Female↗
PubMed1995

Separation of sequence requirements for HSV-1 Vmw110 multimerisation and interaction with a 135-kDa cellular protein.

Herpes simplex virus type 1 immediate-early polypeptide Vmw110 (ICP0) is a general transactivator of gene expression in transfection assays and is required for the fully efficient onset of viral lytic replication. It has also been implicated in the process of viral reactivation from latency. Its mechanism of action is unknown, but any involvement in latency requires interactions between viral and host factors. We have previously shown that Vmw110 binds to a 135-kDa cellular protein. In this paper we define a short region towards the C-terminal end of Vmw110 that is required for the 135-kDa protein interaction in virus-infected cells and in vitro. We also confirm that the C-terminal region of Vmw110 contains residues that are responsible for the multimerisation of the protein; these sequences are at least partially distinct from those involved in 135-kDa binding. Both multimerisation and 135-kDa protein interaction are required for full viral infectivity, and elimination of these functions affects the normal interactions between Vmw110 and cellular nuclear structures that contain the PML protein.

Animals↗