TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study

Background

Thromboelastography^® (TEG) utilizes kaolin, an intrinsic pathway activator, to assess clotting function. Recent published studies suggest that TEG results are commonly normal in patients receiving warfarin, despite an increased International Normalized Ratio (INR). Because RapidTEG? includes tissue factor, an extrinsic pathway activator, as well as kaolin, we hypothesized that RapidTEG would be more sensitive in detecting a warfarin-effect.

Methods

Included in this prospective study were 22 consecutive patients undergoing elective cardioversion and receiving warfarin. Prior to cardioversion, blood was collected to assess INR, Prothrombin Time, TEG, and RapidTEG.

Results

INR Results: 2.8?±?0.5 (1.6 to 4.2). Prothrombin Time Results: 19.1?±?2.2 (13.9. to 24.3). TEG Results (Reference Range): R-Time: 8.3?±?2.7 (2–8); K-Time: 2.1?±?1.4 (1–3); Angle: 62.5?±?10.3 (55–78); MA: 63.2?±?10.3 (51–69); G: 9.4?±?3.5 (4.6-10.9); R-Time within normal range: 10 (45.5%) with INR 2.9?±?0.3; Correlation coefficients for INR and each of the 5 TEG variables were insignificant (P?>?0.05). RapidTEG Results (Reference Range): ACT: 132?±?58 (86–118); K-Time: 1.2?±?0.5 (1–2); Angle: 75.4?±?5.2 (64–80); MA: 63.4?±?5.1 (52–71); G: 8.9?±?2.0 (5.0-11.6); ACT within normal range: 9 (40.9%) with INR 2.7?±?0.5; Correlation coefficients for INR and each of the 5 RapidTEG variables were insignificant (P?>?0.05).

Conclusions

TEG, using kaolin activation, and RapidTEG, with kaolin and tissue factor activation, were normal in a substantial percent of warfarin patients, despite an increased INR. The false-negative rate for detecting warfarin coagulopathy with either test is unacceptable. The lack of correlation between INR and all TEG and RapidTEG components further indicates that these methodologies are insensitive to warfarin effects. Findings suggest that intrinsic pathway activation may mitigate detection of an extrinsic pathway coagulopathy.     

Effects of the components of positive airway pressure on work of breathing during bronchospasm

Introduction

Partial assist ventilation reduces work of breathing in patients with bronchospasm; however, it is not clear which components of the ventilatory cycle contribute to this process. Theoretically, expiratory positive airway pressure (EPAP), by reducing expiratory breaking, may be as important as inspiratory positive airway pressure (IPAP) in reducing work of breathing during acute bronchospasm.

Method

We compared the effects of 10 cmH₂O of IPAP, EPAP, and continuous positive airwaypressure (CPAP) on inspiratory work of breathing and end-expiratory lung volume (EELV) in a canine model of methacholine-induced bronchospasm.

Results

Methacholine infusion increased airway resistance and work of breathing. During bronchospasm IPAP and CPAP reduced work of breathing primarily through reductions in transdiaphragmatic pressure per tidal volume (from 69.4 ± 10.8 cmH₂O/l to 45.6 ± 5.9 cmH₂O/l and to 36.9 ± 4.6 cmH₂O/l, respectively; P < 0.05) and in diaphragmatic pressure–time product (from 306 ± 31 to 268 ± 25 and to 224 ± 23, respectively; P < 0.05). Pleural pressure indices of work of breathing were not reduced by IPAP and CPAP. EPAP significantly increased all pleural and transdiaphragmatic work of breathing indices. CPAP and EPAP similarly increased EELV above control by 93 ± 16 ml and 69 ± 12 ml, respectively. The increase in EELV by IPAP of 48 ± 8 ml (P < 0.01) was significantly less than that by CPAP and EPAP.

Conclusion

The reduction in work of breathing during bronchospasm is primarily induced by the IPAP component, and that for the same reduction in work of breathing by CPAP, EELV increases more.     

Syntheses and Radiosyntheses of Two Carbon-11 Labeled Potent and Selective Radioligands for Imaging Vesicular Acetylcholine Transporter

Purpose

The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. The syntheses and C-11 labeling of two potent enantiopure VAChT inhibitors are reported here.

Procedures

Two VAChT inhibitors, (±)-2 and (±)-6, were successfully synthesized. A chiral HPLC column was used to resolve the enantiomers from each corresponding racemic mixture for in vitro characterization. The radiosyntheses of (?)-[¹¹C]2 and (?)-[¹¹C]6 from the corresponding desmethyl phenol precursor was accomplished using [¹¹C]methyl iodide or [¹¹C]methyl triflate, respectively.

Results

The synthesis of (?)-[¹¹C]2 was accomplished with 40–50 % radiochemical yield (decay-corrected), SA?>?480 GBq/μmol (EOB), and radiochemical purity >99 %. Synthesis of (?)-[¹¹C]6 was accomplished with 5–10 % yield, SA?>?140 GBq/μmol (EOB), and radiochemical purity >97 %. The radiosynthesis and dose formulation of each tracer was completed in 55–60 min.

Conclusions

Two potent enantiopure VAChT ligands were synthesized and ¹¹C-labeled with good radiochemical yield and specific activity.     

Evaluation of heated humidifiers for use on intubated patients: a comparative study of humidifying efficiency,flow resistance,and alarm functions using a lung model

Objective. Evaluation of humidification efficiency, flow resistance, and alarm functions of heated humidifiers (HH;(Kendall-Aerodyne-delta, Fisher&;Paykel-MR 730; Dräger-Aquapor; Puritan-Bennett-Cascade II) in accordance with ISO/EN-8185:1997 and on a ventilated lung model in accordance with ISO/EN-9360:2000. Methods. Humidification efficiency was evaluated by (a) measuring the water content of the inspiratory air on perfusion with different gas flows, (b) measuring the water loss of a lung model, and (c) simultaneous measurement of the in- and expiratory water content with a capacitive hybrid sensor. The resistance characteristics were measured, the data were compared with a mathematical approximation. The alarm functions were determined. Results. The humidification efficiency of HHs is a function of gas flow and design characteristics. In HHs with tube heating it is possible to make settings at which the inspiratory humidity falls below the minimal value of 33 mgH₂O/l stipulated by ISO/EN-8185:1997. The inspiratory resistances extend from 0.5 to 4.4 cmH₂O l^–1 s^–1; the expiratory flow resistances of the devices are low. The alarm functions of HHs with tube heating are inadequate for cases involving both "dry start" and "running dry." Conclusions. Efficiency data that allow a direct comparison with heat and moisture exchangers data according to ISO/EN-9360:2000 can also be determined for HH. HH do not prevent pulmonary water losses in intubated patients. These losses can exceed the physiological range. The airway resistance of the Cascade II prohibits its use in spontaneously breathing patients. The warning and shut-off features of HH are unacceptable and hazardous.     

In Vitro and In Vivo Characterization of Two C-11-Labeled PET Tracers for Vesicular Acetylcholine Transporter

Purpose

The vesicular acetylcholine transporter (VAChT) is a specific biomarker for imaging presynaptic cholinergic neurons. Herein, two potent and selective ¹¹C-labeled VAChT inhibitors were evaluated in rodents and nonhuman primates for imaging VAChT in vivo.

Procedures

For both (?)-[¹¹C]2 and (?)-[¹¹C]6, biodistribution, autoradiography, and metabolism studies were performed in male Sprague Dawley rats. Positron emission tomography (PET) brain studies with (?)-[¹¹C]2 were performed in adult male cynomolgus macaques; 2 h dynamic data was acquired, and the regions of interest were drawn by co-registration of the PET images with the MRI.

Results

The resolved enantiomers (?)-2 and (?)-6 were very potent and selective for VAChT in vitro (K _i ?35-fold selectivity for VAChT vs. σ receptors); both radioligands, (?)-[¹¹C]2 and (?)-[¹¹C]6, demonstrated high accumulation in the VAChT-enriched striatum of rats. (?)-[¹¹C]2 had a higher striatum to cerebellum ratio of 2.4-fold at 60 min; at 30 min, striatal uptake reached 0.550?±?0.086 %ID/g. Uptake was also specific and selective; following pretreatment with (±)-2, striatal uptake of (?)-[¹¹C]2 in rats at 30 min decreased by 50 %, while pretreatment with a potent sigma ligand had no significant effect on striatal uptake in rats. In addition, (?)-[¹¹C]2 displayed favorable in vivo stability in rat blood and brain. PET studies of (?)-[¹¹C]2 in nonhuman primates indicate that it readily crosses the blood-brain barrier (BBB) and provides clear visualization of the striatum; striatal uptake reaches the maximum at 60 min, at which time the target to nontarget ratio reached ~2-fold.

Conclusions

The radioligand (?)-[¹¹C]2 has high potential to be a suitable PET radioligand for imaging VAChT in the brain of living subjects.     

The efficiency of preoperative evaluation: A comparison of computerized and paper recording systems

Objective. We designed and implemented a preoperative evaluation record system with seven networked computers for use by physicians and other medical staff. This study compared the efficiency of the new computerized system with that of the paper system.Methods. We reviewed data from preoperative evaluations completed from November 1990 through December 1992. Data were analyzed automatically (Borland C program) for two intervals: (1) the waiting period, defined as the time the patient entered the waiting room until he or she entered the examination room; and (2) the examination period, defined as the time the patient entered the examination room until an evaluation form was printed. Data were obtained for 2,511 evaluations on paper and 8,342 by computer.Results. The average waiting period with the paper system was 56.1 ± 44.8 min; the average waiting period with the computerized system was 59.1 ± 47.0 min. The average examination period was nearly identical for both systems: 27.5 ± 23.6 min for the paper system; 28.5 ± 22.7 min for the computerized system.Conclusion. The computerized system required no more examination time than the manual system. In addition, we speculate that time is saved at other points of patient care by the legible, instantly retrievable preoperative evaluations that the computerized system produces.     

Quantification of Iron-Labeled Cells with Positive Contrast in Mouse Brains

Purpose

To quantify small amounts of iron-labeled cells in mouse brains with magnetic resonance imaging (MRI).

Procedures

Iron-labeled cells (from 500 to 7,500) were stereotaxically transplanted into the brain of living mice that were subsequently imaged with MRI at 4.7 T. We compared four quantitative methods: (1) T2 relaxometry, (2) T2* relaxometry, (3) the volume of the cloverleaf hypointense artifact generated on T2*-weighted images, and (4) the volume of the cloverleaf hyperintense artifact generated on positive contrast images.

Results

The methods based on relaxometry, whether T2 or T2*, did not correlate with the number of injected cells. By contrast, those based on measurement of cloverleaf artifact volume, whether using negative or positive enhancement, showed a significant linear relationship for the given range of cells (R [0.92?C0.95], p?<?0.05).

Conclusions

T2* artifact volume imaging (negative or positive) appears promising for the quantification of magnetically labeled cells following focal injection in the brain.     

Monitoring body-cors temperature from the trachea: Comparison between pulmonary artery,tympanic, esophageal,and rectal temperatures

Introduction. We designed an endotracheal tube (ETT) for acquiring body-tore temperature from the trachea. This ETT had two temperature sensors, one attached to the inside surface of the cuff, the other mounted on the ETT shaft underneath the cuff. The ETT was evaluatedin vitro and in dogs to determine: 1) optimal position of temperature sensors and 2) the responsiveness, accuracy, and resistance to ventilatory artifacts.Methods.In vitro. An artificial trachea assessed the response-time and accuracy of ETT temperature sensors to abrupt temperature changes and ventilatory flow-rates.In vivo. Body temperature in 5 dogs was lowered to approximately 26°C then elevated toward 39°C using a heat exchanger during carotid jugular bypass. ETT temperature measurements were compared simultaneously with those from the artificial trachea (in vitro) or from the pulmonary artery, tympanic cavity, esophagus, and rectum of dogs using dry and humidified gas.Results. Cuff temperature sensor responded quickly and accurately to temperature changes and was less prone than the tube sensor to ventilatory and humidity artifacts. During carotid-jugular bypass,in vivo tube and cuff mean temperatures averaged 1.4°C and 0.36°C lower, respectively, than pulmonary artery temperatures. There were no statistical differentes (P > 0.05) between cuff temperatures and those measured from the pulmonary artery, tympanic cavity, esophagus, and rectum. Heating and humidifying the inspiratory gas of dogs with a water-bath humidifer or heat moisture exchanger (HME) had minimal effects on the cuff temperature sensor. An in-line HME increasedin vivo tube temperature from baseline values by 1.13 ± 0.80 °C, while cuff temperature increased by 0.21 ±0.24°C.Conclusion. The cuff of the ETT is a reliable site for measuring body-tore temperature in intubated patients.     

Does impedance cardiography reliably estimate left ventricular ejection fraction?

Objective. The objective of our study was to evaluate impedance cardiography (IMP) as a noninvasive method to determine the left ventricular ejection fraction (LVEF).Methods. A total of 24 patients, 8 men and 16 women, aged 45.0 ± 12.9 years, participated in the study. They used cardiotoxic chemotherapeutic drugs or suffered from cardiac failure. LVEF was measured by means of IMP (LVEF_imp) and radionuclide ventriculography (LVEF_nuc). LVEF_imp was calculated in three ways. Capan and colleagues [13] proposed a formula in which LVEF (LVEF_Cap) can be calculated from the systolic time intervals, namely, left ventricular ejection time and preejection time. Judy and colleagues [14] described a systolic (S) and a diastolic (D) part in the first derivative curve of the impedance signal. The ratio S/D might equal the LVEF (LVEF_Jud). A new LVEF calculation was introduced (LVEFimp) in this study based on the first derivative of the impedance signal, the thoracic impedance, and heart rate.Results. Mean LVEF_Cap was 59.9 ± 8.4%, which did not differ from LVEF_nuc (59.9 ± 7.1%). However the correlation between both methods was not significant (γ = 0.29). Mean LVEF_Jud was 63.9 ± 17.4%, which was not significantly different from LVEF_nuc, with a fair correlation (γ = 0.55). Mean LVEF_imp was 59.2 ± 9.4%, with a better correlation with radionuclide ventriculography (γ = 0.75).Conclusions. The results of this study indicate that the equations that have been used until now can be improved. The new equation provides reliable LVEF values in this group of patients.     

Measurement of CO2 response with the breath-by-breath automatic acquisition of the breathing pattern and occlusion pressure

Objective. Our objective is to present a methodology for the automated acquisition and storage of BP and P_0.1 during a CO₂ rebreathing test.Methods. The system consists of a microcomputer with additional circuits and an automatic electronically controlled valve to occlude the inspiratory airway. Data collection and data processing are separate programs. Airway pressure and flow are digitized at a 100-Hz rate, whilePetCO₂ is determined and P_0.1 is measured on a breath-by-breath basis. Off-line processing calculates the BP variables, generates a correlation matrix (Ve/PetCO₂,Ttot/PetCO₂,Ti/PetCO₂,Te/PetCO₂, [Vt/Ti]/PetCO₂, [Ti/Ttot]/PetCO₂, P_0.1/PetCO₂), and edits graphic data. The accuracy of the volume and pressure measurements was tested by comparing known volumes provided by a syringe (n=100) and a series of pressures controlled by a water manometer (n=41) on the one hand, with volumes and pressures measured by the device. The accuracy of the time intervals and P_0.1 was assessed by comparing in 10 healthy subjects the values measured manually on a graphic recording with those provided by the device (n=170).Results. Volumes: V_measured=0.99×V_controlled,r=0.99,p<0.001. Pressures: P_measured=0.97×P_controlled+0.09,r=0.98,p<0.001. Inspiratory time:Ti _automatic=0.91×Ti _graphic+0.22,r=0.93,p<0.001. Expiratory time:Te _automatic=0.93×Te _graphic+0.34,r=0.95,p<0.001. Occlusion pressure: P_{0.1 automatic}=0.95×P_{0.1 graphic}+0.62,r=0.94,p<0.001. Reproducibility was assumed to be represented by the intraindividual coefficient of variation of the CO₂ response. The comparison of an automatic breath-to-breath method with a graphic manual recording revealed significantly less variability with the former (Ve/PetCO₂: 15.2±4.5% vs 22.5±6.3%,p<0.01; P_0.1/PetCO₂: 8.3±4.3% vs 19.7±7.2%,p<0.001; [Vt/Ti]/PetCO₂: 9.1±3.5% vs 14.5±5.3%,p<0.05).Conclusion. Our automated acquisition and storage of waveforms and breath-by-breath determination of BP and P_0.1 provide an easy and thorough analysis of the respiratory response to CO₂ and decrease the variability of the results.     

Synthesis and Evaluation of 13N-Labelled Azo Compounds for β-Amyloid Imaging in Mice

Purpose

The aim of the present study was to develop short half-lived tools for in vitro and in vivo β-amyloid imaging in mice, for which no suitable PET tracers are available.

Procedures

Five ¹³N-labelled azo compounds (1–5) were synthesized using a three-step process using cyclotron-produced [¹³N]NO₃ ^?. Biodistribution studies were performed using positron emission tomography–computed tomography (PET–CT) on 20-month-old healthy, wild-type (WT) mice. In vivo and in vitro binding assays were performed using PET-CT and autoradiography, respectively, on 20-month-old healthy (WT) mice and transgenic (Tg2576) Alzheimer's disease model mice.

Results

¹³N-labelled azo compounds were prepared with decay corrected radiochemical yields in the range 27?±?4 % to 39?±?4 %. Biodistribution studies showed good blood–brain barrier penetration for compounds 1 and 3–5; good clearance data were also obtained for compounds 1–3 and 5. Compounds 2, 3 and 5 (but not 1) showed a significant uptake in β-amyloid-rich structures when assayed in in vitro autoradiographic studies. PET studies showed significant uptake of compounds 2 and 3 in the cortex of transgenic animals that exhibit β-amyloid deposits.

Conclusions

The results underscore the potential of compounds 2 and 3 as in vitro and in vivo markers for β-amyloid in animal models of Alzheimer's disease.     

Fully Automated Radiosynthesis of 2-[18F]Fludarabine for PET Imaging of Low-Grade Lymphoma

Purpose

An efficient and fully automated radiosynthesis of 2-[¹⁸F]fluoro-9-β-d-arabinofuranosyl-adenine (2-[¹⁸F]fludarabine, [¹⁸F]-5) based on a GE TRACERlab? FX-FN module has been developed.

Procedures

A 2-nitro purine derivative 3 was developed as precursor for labeling with fluorine-18. The radiosynthesis of [¹⁸F]-5 was performed in two steps in a single reactor with an intermediary purification on Sep-Pak® silica which involved the addition of a three-way valve on the original module. After hydrolysis, [¹⁸F]-5 was purified by semi-preparative high-pressure liquid chromatography (HPLC) and a quality control was established.

Results

The labeling precursor 3 was obtained in 45 % overall yield. Nucleophilic substitution with K¹⁸F/K_2.2.2 afforded protected 2-[¹⁸F]fludarabine ([¹⁸F]-4) in 73?±?4 % , radiochemical yield (decay corrected to the end of bombardment (EOB)) and based on the initial [¹⁸F]F^? activity. An aqueous ammonia/methanol solution was used for the deprotection reaction and gave the desired [¹⁸F]-5 in 67?±?3 % yield after 20 min at 70 °C based on HPLC profile.

Conclusions

The process afforded pure 2-[¹⁸F]fludarabine in 48?±?3 % yield (decay corrected to the EOB) in 85 min, with a specific activity of 310?±?72 GBq/μmol at the end of synthesis (EOS) and a radiochemical purity up to 99 %.     

Effects of Chelator Modifications on 68Ga-Labeled [Tyr3]Octreotide Conjugates

Purpose

Somatostatin receptors (SSTR) have been reported as promising targets for imaging agents for cancer. Recently, ⁶⁸Ga-DOTATOC-based PET imaging has been used successfully for diagnosis and management of SSTR-expressing tumors. The purpose of this study was to evaluate the influence of chelator modifications and charge on ⁶⁸Ga-labeled peptide conjugates.

Procedures

We have synthesized a series of [Tyr³]octreotide conjugates that consisted of different NOTA-based chelators with two to five carboxylate moieties, and compared our results with ⁶⁸Ga-DOTATOC in both in vitro and in vivo studies.

Results

With the exception of ⁶⁸Ga-1 (three carboxylates), the increased number of carboxylates on the NOTA-based chelators resulted in a reduced binding affinity and internalization. Additionally, the tumor uptake for ⁶⁸Ga-2 (four carboxylates) and ⁶⁸Ga-3 (five carboxylates) was reduced compared to that of ⁶⁸Ga-DOTATOC (three carboxylates) and ⁶⁸Ga-NO2ATOC (two carboxylates) and ⁶⁸Ga-1 (three carboxylates) at 2 h p.i. suggesting the presence of an optimal charge for this compound.

Conclusions

Chelator modifications can lead to the altered pharmacokinetics. These results may impact further design considerations for peptide-based imaging agents.     

The assessment of transpulmonary pressure in mechanically ventilated ARDS patients

Purpose

The optimal method for estimating transpulmonary pressure (i.e. the fraction of the airway pressure transmitted to the lung) has not yet been established.

Methods

In this study on 44 patients with acute respiratory distress syndrome (ARDS), we computed the end-inspiratory transpulmonary pressure as the change in airway and esophageal pressure from end-inspiration to atmospheric pressure (i.e. release derived) and as the product of the end-inspiratory airway pressure and the ratio of lung to respiratory system elastance (i.e. elastance derived). The end-expiratory transpulmonary pressure was estimated as the product of positive end-expiratory pressure (PEEP) minus the direct measurement of esophageal pressure and by the release method.

Results

The mean elastance- and release-derived transpulmonary pressure were 14.4 ± 3.7 and 14.4 ± 3.8 cmH₂O at 5 cmH₂O of PEEP and 21.8 ± 5.1 and 21.8 ± 4.9 cmH₂O at 15 cmH₂O of PEEP, respectively (P = 0.32, P = 0.98, respectively), indicating that these parameters were significantly related (r ² = 0.98, P < 0.001 at 5 cmH₂O of PEEP; r ² = 0.93, P < 0.001 at 15 cmH₂O of PEEP). The percentage error was 5.6 and 12.0 %, respectively. The mean directly measured and release-derived transpulmonary pressure were ?8.0 ± 3.8 and 3.9 ± 0.9 cmH₂O at 5 cmH₂O of PEEP and ?1.2 ± 3.2 and 10.6 ± 2.2 cmH₂O at 15 cmH₂O of PEEP, respectively, indicating that these parameters were not related (r ² = 0.07, P = 0.08 at 5 cmH₂O of PEEP; r ² = 0.10, P = 0.53 at 15 cmH₂O of PEEP).

Conclusions

Based on our observations, elastance-derived transpulmonary pressure can be considered to be an adequate surrogate of the release-derived transpulmonary pressure, while the release-derived and directly measured end-expiratory transpulmonary pressure are not related.     

An optimized set-up for helmet noninvasive ventilation improves pressure support delivery and patient�Cventilator interaction

Objective

To test the effects on mechanical performance of helmet noninvasive ventilation (NIV) of an optimized set-up concerning the ventilator settings, the ventilator circuit and the helmet itself.

Subjects and methods

In a bench study, helmet NIV was applied to a physical model. Pressurization and depressurization rates and minute ventilation (MV) were measured under 24 conditions including pressure support of 10 or 20?cmH₂O, positive end expiratory pressure (PEEP) of 5 or 10?cmH₂O, ventilator circuit with ??high??, ??intermediate?? or ??low?? resistance, and cushion deflated or inflated. In a clinical study pressurization and depressurization rates, MV and patient?Cventilator interactions were compared in six patients with acute respiratory failure during conventional versus an ??optimized?? set-up (PEEP increased to 10?cmH₂O, low resistance circuit and cushion inflated).

Results

In the bench study, all adjustments simultaneously applied (increased PEEP, inflated cushion and low resistance circuit) increased pressurization rate (46.7?±?2.8 vs. 28.3?±?0.6?%, p?<?0.05), depressurization rate (82.9?±?1.9 vs. 59.8?±?1.1?%, p????0.05) and patient MV (8.5?±?3.2 vs. 7.4?±?2.8?l/min, p?<?0.05), and decreased leaks (17.4?±?6.0 vs. 33.6?±?6.0?%, p?<?0.05) compared to the basal set-up. In the clinical study, the optimized set-up increased pressurization rate (51.0?±?3.5 vs. 30.8?±?6.9?%, p?<?0.002), depressurization rate (48.2?±?3.3 vs. 34.2?±?4.6?%, p?<?0.0001) and total MV (27.7?±?7.0 vs. 24.6?±?6.9?l/min, p?<?0.02), and decreased ineffective efforts (3.5?±?5.4 vs. 20.3?±?12.4?%, p?<?0.0001) and inspiratory delay (243?±?109 vs. 461?±?181?ms, p?<?0.005).

Conclusions

An optimized set-up for helmet NIV that limits device compliance and ventilator circuit resistance as much as possible is highly effective in improving pressure support delivery and patient?Cventilator interaction.     

The influence of age and BMI on intervertebral disc height and oropharyngeal airway in Japanese men and women

Objective

Intervetebral disc height changes with both age and increasing body mass index (BMI), known risk factors for obstructive sleep apnea (OSA). We studied the relationship of body mass index (BMI) and aging in the neck structures to disc compression and oropharyngeal airway size and shape.

Materials and methods

The intervertebral disc (IVD), neck and airway volumes were measured at the C2 level only from Computerized Tomography scans using a semi-automatic segmentation tool. The change of intervertebral disc height/volume with age and BMI were examined in 38 consecutive Japanese patients (Male: 19, Female: 19), group matched for age (men: 52.2 ± 15.36 years; women: 52.4 ± 17.37) and BMI (men: 23.1 ± 2.97 m/kg²; women: 21.6 ± 4.03 m/kg²).

Results

In this study, the intervertebral disc volume as a percent of neck volume was larger in men than in women (P = 0.039), and the intervertebral disc volume (r = ?0.588; P = 0.013) and height (r = ?0.510; P = 0.037) decreased with increasing age-adjusted BMI in males only. Age was not significantly correlated with any of the volumes. The intervertebral airway volume significantly decreased with increasing age-adjusted BMI in our female subjects (r = ?0.588; P = 0.013).

Conclusion

In our Japanese volunteer population, the intervertebral disc is compressed vertically with the increase of BMI in males only, and the oropharyngeal airway volume decreases with increasing BMI in females only. These results may be useful in assessment of OSA risk.     

Evaluation of a fiberoptic system for airway pressure monitoring

Objective..Our objective was to evaluate the accuracy of a novel fiberoptic system for airway pressure measurement at the carinal end of the endotracheal tube in an in vitro pediatric lung model.Methods. A fiberoptic pressure measuring system was compared to the conventional method of measuring airway pressure with a pneumatic transducer using a test lung model. Pressure measurements were obtained using four endotracheal tubes of various internal diameters (ID) (3 to 6 mm) during simulated spontaneous and mechanical ventilation. Airway pressure was measured using both methods simultaneously and the results were compared by statistical analysis.Results. Airway pressure measured by the fiberoptic system was not significantly different from measurements obtained by the pneumatic transducer except when using the 3-mm and 4-mm ID endotracheal tubes during mechanical ventilation.Conclusions. We conclude that the fiberoptic system provides accurate and precise measurement of airway pressure during spontaneous and mechanical ventilation. Additionally, the statistically significant differences obtained for 3- and 4-mm tubes are not large enough to be clinically significant. The fiberoptic system offers advantages over the pneumatic system for measuring the airway pressure. These advantages include decreased chance of false pressure measurement secondary to occlusion with water or mucous, less chance of kinking, and, possibly, more rapid response to pressure changes due to the mechanical ventilator.     

A Grid-Based Hiv Expert System

Objectives.This paper addresses Grid-based integration and access of distributed data from infectious disease patient databases, literature on in-vitro and in-vivo pharmaceutical data, mutation databases, clinical trials, simulations and medical expert knowledge. Methods. Multivariate analyses combined with rule-based fuzzy logic are applied to the integrated data to provide ranking of patient-specific drugs. In addition, cellular automata-based simulations are used to predict the drug behaviour over time. Access to and integration of data is done through existing Internet servers and emerging Grid-based frameworks like Globus. Data presentation is done by standalone PC based software, Web-access and PDA roaming WAP access. The experiments were carried out on the DAS2, a Dutch Grid testbed. Results. The output of the problem-solving environment (PSE) consists of a prediction of the drug sensitivity of the virus, generated by comparing the viral genotype to a relational database which contains a large number of phenotype-genotype pairs.Conclusions. Artificial Intelligence and Grid technology are effectively used to abstract knowledge from the data and provide the physicians with adaptive interactive advice on treatment applied to drug resistant HIV. An important aspect of our research is to use a variety of statistical and numerical methods to identify relationships between HIV genetic sequences and antiviral resistance to investigate consistency of results.     

Assessment of Airway Distribution of Transnasal Solutions in Mice by PET/CT Imaging

Purpose

Transnasal administration is one of the most common routes for allergen challenge in mouse models of airway diseases. Although this technique is widely used, neither the amount of allergen that reaches the lung nor its airway distribution has been well established. We used positron emission tomography (PET) and computed tomography (CT) to examine the anatomical distribution of a solution containing a tracer immediately after transnasal delivery and to determine the possible influence of age and administered volume.

Procedures

Forty-six female BALB/c mice were divided into three groups according to instillation volume and age: (A) 15 μl, 8–10 weeks old (N?=?10), (B) 30 μl, 8–10 weeks old (N?=?20), and (C) 30 μl, 32 weeks old (N?=?16). Anesthetized animals underwent a dynamic scan in a dedicated small-animal PET scanner immediately after transnasal administration of a solution containing ¹⁸FDG. Regions of interest were used to obtain quantitative data. Animals were also imaged with a small-animal CT scanner to obtain complementary anatomical information.

Results

Mean?±?SD (5.69?±?4.51%) of the solution administered reached the lungs in group A, 41.84?±?8.03% in group B, and 36.65?±?16.15% in group C. A comparable percentage was delivered to the left and right lungs in all the groups. Analysis of variance revealed a significant difference between the groups in the proportion of the solution that reached the lungs depending on the injection volume (P?Conclusions In this first report on quantitative imaging by PET and CT in small animals, we confirmed the suitability of the transnasal route with an instilled volume of 30 μl delivering fluids into the lower airways, although only about 40% of the dose reaches the lungs.     

Effects of piroximone on the right ventricular function in severe heart failure patients

Objectives

To assess the effects of piroximone, a phosphodiesterase inhibitor, on right ventricular function in patients with heart failure.

Design

Randomized study: patients were randomly assigned to the piroximone infusion rate of 5 or 10 μg/kg/min.

Setting

Cardiologic intensive care unit.

Patients

12 consecutive patients with severe heart failure.

Interventions

Right heart catheterization was performed using a Swan-Ganz ejection fraction thermodilution catheter.

Measurements and results

Measurements of right ventricular ejection fraction (RVEF), end-diastolic and end-systolic right ventricular volumes were obtained using the thermodilution principle. To determine contractility indexes, the relationships between end-systolic pulmonary arterial pressure (ESPAP) over right ventricular end-systolic volume (RVESV) and ESPAP over RVEF were calculated during the infusion of prostacyclin at incremental infusion rates of 2, 4, 6 and 8 ng/kg/min. The slope of the relation between ESPAP over RVESV shifted during piroximone therapy from 7.635±1.632 to 1.975±0.432 (p<0.01) and from 6.092±1.99 to 1.028±0.853 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively. The slope of the relation between ESPAP over RVEF decreased from ?0.414±0.296 to ?0.821±0.257 (p<0.01) and from ?0.127±0.048 to ?0.533±0.135 (p<0.05) at 5 and 10 μg/kg/min piroximone infusion, respectively.

Conclusions

This study suggests a positive action of piroximone on right ventricular contractility at these 2 dosages. This approach using this type of catheter allowed us to determine right ventricular inotropic indexes.