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.     

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 %.     

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.     

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.     

Assessment of hypothermia with a new “tympanic” thermometer

Objective. Rapid and accurate core temperature measurement is vitally important in trauma patients, especially in those with accidental hypothermia. We tested a new aural thermometer to measure “tympanic” temperatures and assessed its accuracy during normothermic and hypothermic cardiopulmonary bypass.Methods. Tympanic, esophageal, and blood temperatures were compared in 10 patients undergoing open-heart surgery. In addition, the stability and reaction time of the tympanic thermometer was evaluated in 5 volunteers in a cold room, with and without facial fanning.Results. We observed a good linear correlation between tympanic and esophageal (r = 0.96) and blood (r = 0.81) temperature measurements during normothermia and hypothermia. There was no evidence of iatrogenic ear lesions in any of the patients. In the cold-room tests, stability was excellent and the time for adjustment of tympanic temperature measurement was about 2 min (with and without facial fanning).Conclusion. The new tympanic thermoprobe is a simple, fast, and reliable device for measuring core temperature. The device was designed particularly for, and may be useful for, patients suffering from accidental hypothermia.     

Thermoregulatory vasoconstriction increases the difference between femoral and radial arterial pressures

Objective. Thermoregulatory vasoconstriction locally increases arterial wall tension and arteriolar resistance, thereby altering physical properties of the arteries. The arterial pressure waveform is an oscillatory phenomenon related to those physical characteristics; accordingly, we studied the effects of thermoregulatory vasomotion on central and distal arterial pressures, using three hydraulic coupling systems having different dynamic responses.Methods. We studied 7 healthy volunteers. Central arterial pressure was measured from the femoral artery and distal pressure was measured from the radial artery, using 10.8-cm long, 20-gauge catheters. Three hydraulic coupling systems were used: (1) a 10-cm-long, 2-mm internal diameter connector; (2) a 150-cm-long, 1-mm internal diameter connector (Combidyn 520-5689, B. Braun, Melsungen, Germany); (3) a 180-cm long, 2-mm internal diameter connector (Medex MX564 and MX562, Medex Inc., Hillard, OH). Brachial artery pressure was measured oscillometrically. Core temperature was measured at the tympanic membrane. The vasomotor index, defined as finger temperature minus room temperature, divided by core temperature minus room temperature, was used to estimate the degree of vasoconstriction. Constriction was considered near maximal when the index was less than 0.1, and minimal when it exceeded 0.75. Measurements were taken every 3 min. Baseline readings were obtained when subjects were warm. They then were cooled by exposure to 20°C to 22°C room air and a circulating-water mattress set at 4°C until 4 index was less than 0.1. They then were rewarmed by increasing water temperature to 42°C and adding a forced-air warmer until the vasomotor index exceeded 0.75. Data were analyzed by ANOVA and linear regression.Results. Thermoregulatory vasoconstriction was associated with marked arterial pressure waveform changes. Radial pressure showed, in lieu of a dicrotic notch, large oscillations of decreasing amplitude. Femoral pressure showed a single diastolic oscillation of smaller amplitude. The waveforms appeared different, depending on the hydraulic coupling system used, artifact being more marked with the longer connectors. On the average, radial systolic pressure exceeded femoral systolic pressure during vasoconstriction; however, during vasodilatation, femoral systolic pressure exceeded radial systolic pressure (p < 0.05). Oscillometric measurements underestimated systolic pressure, and did so more markedly during vasoconstriction. There were no differences in the values of mean and diastolic pressures.Conclusion. Thermoregulatory vasoconstriction alters radial arterial pressure waveform, artifactually increasing its peak systolic pressure compared with the femoral artery. Poor dynamic responses of recording systems further distort the waveforms. Consequently, radial artery pressure may be misleading in vasoconstricted 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.     

Monitoring normal and aberrant electrocardiographic activity from an endotracheal tube: Comparison of the surface,esophageal, and tracheal electrocardiograms

Introduction. We designed an endotracheal (ET) tube with orthogonally spaced ECG cuff electrodes. This ET tube was evaluated in dogs and sheep to determine (1) whether ECGs recorded from our tube were sufficient to make accurate clinical decisions concerning heart rate and rhythm; and (2) whether metallic cuff electrodes in direct contact with the trachea could induce mucosal burn injury during episodes of defibrillation.Methods. Using experimental animals, we obtained ECGs from their tracheae and compared our findings with ECGs obtained from surface and esophageal electrodes. The electrical activity of the heart was modified by increasing the depth of anesthesia, occluding the left coronary artery, and administering beta-adrenergic drugs. Before the dogs were euthanized, they were subjected to episodes of transthoracic and intrathoracic defibrillation at energy levels of 200 to 400 J. A postmortem pathological examination of the trachea was performed to determine the incidence of mucosal burn injury.Results. Tracheal electrocardiography provided valid information on heart-rate monitoring and certain morphology profiles. The R-R, PR, QRS, and QT intervals measured from the trachea had a correlation of 1.0, 0.96, 0.83, and 0.98, respectively, when compared with the same intervals obtained from surface electrodes. Two tracheae subjected to intrathoracic defibrillation at >300 J revealed evidence of minor burn injury. Some localized epithelium loss was displayed in all tracheae; we attributed this to tracheal intubation.Conclusion. Tracheal electrocardiography may be useful in trauma patients who require intubation where injury precludes placement of chest ECG electrodes.     

Comparison of Transoral Power-Assisted Endoscopic Adenoidectomy to Curettage Adenoidectomy

Introduction

The aim of this prospective and randomized study was to compare patients who underwent curettage adenoidectomy (CA) or transoral power-assisted endoscopic adenoidectomy (PAEA) performed as isolated procedures by a single surgeon over a period of 7 years. The success of an adenoidectomy has been evaluated by assessing the amount of reduction in the adenoid size and the symptomatic improvement at the sixth postoperative month.

Methods

Patients?? nasal airway obstruction was graded by the parents of the patient on a visual analog scale (VAS), with a range from 0 to 10, with grade 10 representing total obstruction. The ratio of the choanal opening obstructed by an adenoid mass was measured and expressed in percentages as representative of the adenoid size. Preoperative and 6-month postoperative adenoid sizes were compared.

Results

Fifty-three patients (CA group 27 patients/PAEA group 26 patients) completed the study. In the CA group, VAS score improved from the preoperative score of 8.63 ± 0.88 to the 6-month score of 2.22 ± 1.01 (P < 0.0001); and in the PAEA group, the preoperative VAS score of 8.69 ± 0.84 improved to 2.08 ± 1.05 in the same period (P < 0.0001). No statistical significance was found when VAS score improvements were compared (P = 0.4569). The average ratio of choanal opening obstructed by an adenoid mass improved from the preoperative ratio of 89.41% ± 6.48% to the 6-month ratio of 7.85% ± 2.28% in the CA group; and the preoperative ratio of 90.19% ± 6.95% in the PAEA group improved to 3.65% ± 1.38% after 6 months. The reduction of adenoid size was significantly superior in PAEA than CA (P < 0.0001). The operative time in PAEA was significantly shorter than that in CA (P < 0.0001).

Conclusion

Although symptomatic improvement at the 6-month follow-up is statistically indifferent, PAEA has been shown to be superior to CA with its superior performance in providing a near-total elimination of the adenoid mass in a shorter operating time.     

Comparison of six methods to calculate airway resistance during mechanical ventilation in adults

Objective. A variety of methods are used to calculate indices of lung mechanics. We conducted this study to compare 6 methods of calculating airway resistance.Methods. Data were recorded from 20 adult mechanically ventilated patients. All were relaxed and breathing in synchrony with the ventilator, and an end-inspiratory pause sufficient to produce a pressure plateau (0.5–1.5 s) was used. Pressure and flow rate were measured at the proximal airway using a calibrated lung mechanics analyzer (VenTrak, Med Science, St Louis, MO). Flow rate, pressure, and volume were printed simultaneously. Airway resistance was calculated using 6 methods: Suter, Krieger, Neergard, Bergman, Comroe, and Jonson.Results. Mean calculated resistances (± SD) (cm H₂O/L/s) were 11.7 ± 4.8 (Suter method), 13.3 ± 5.0 (Krieger method), 14.9 ± 5.3 (Neergard method), 25.0 ± 6.6 (Bergman method), 24.7 ± 6.4 (Comroe method), and 26.9 ± 4.8 (Jonson method). By repeated measures analysis of variance, these differences were significant (p < 0.001). Using Scheffe analysis, no difference was found between the calculations using the Bergman, Comroe, and Jonson methods; these were significantly greater than the other 3 methods (p < 0.05).Conclusions. Methods that evaluate expiratory resistance (Comroe, Bergman, and Jonson) produce higher values than methods that evaluate inspiratory resistance (Suter and Neergard) or a combination of inspiratory and expiratory resistance (Krieger). Because of these differences, investigators should clearly describe their calculations when reporting airway resistance values.     

Magnetron-based inline microwave fluid warmer

Objective. To develop an in-line microwave fluid warming system that eliminates the difficulties of uneven heating that are characteristic of batch-mode microwave fluid warmers.Methods. Using a commercial microwave oven, we developed a method for warming fluid as it flowed through tubing along a defined path in the oven's cavity. Algorithms utilizing either proportional or adaptive control were used to control microwave heating cycles by varying the heating pulse-width during 3-second epochs. Methods of fluid entry and exit were devised to minimize microwave leakage. Heating performance was tested using icewater at multiple flow rates from 18 mL/min to 105 mL/min.Results. In all warming tests, the system achieved temperature control without exceeding the maximum temperature allowable based on American Association of Blood Banks requirements. The adaptive control maintained the set temperature, with peak-to-peak oscillations of 2°C or less. Microwave leakage was below the commercially required limit for home microwave appliances.Conclusions. The combination of proportional and adaptive control is successful in controlling the permanent magnet magnetron microwave energy to heat the icewater tested. The in-line microwave warmer has the potential to become a successful medical fluid warmer. More study is needed to determine the stability of the control system under clinical conditions, and to evaluate its utility for warming blood.     

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.     

An analysis of the effect of venous resistance on the performance of gravity-fed intravenous infusion systems

Objective. Our objective was to assess the effect of venous resistance in a clinically relevant range on flow rates through intravenous (IV) cannulae.Methods. Since resistances in series are additive, the sum of the resistance of the IV cannula and the vein equates to the total resistance to flow. Using resistance data from earlier work, the total resistance for various combinations of cannula and vein size was calculated, allowing a prediction to be made of the comparative flow rates between these combinations for a given driving pressure. Next, the clinical situation was simulated by measuring flow rates through IV cannulae connected in series to a variety of infusion devices with resistances known to be within the range of clinically relevant venous resistance.Results. The effect of venous resistance was greatest on largebore cannulae, with significant reductions in flow occurring when even low levels of venous resistance were added. Throughout much of the range of venous resistances encountered clinically, total flows through two small-gauge cannulae exceeded that through a single large-gauge cannula.Conclusion. To achieve maximum benefit from a large-bore cannula, a suitably large vein must be chosen. Further, where venous access is difficult and high flow potential from an infusion system is required, two separate infusions through small cannulae may be a preferable option to a single large bore.     

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.     

Entwicklung eines Migräneprophylaxe-Screeninginstruments (MPS)

The aim of the present study was to develop a screening tool to aid non-headache specialists, like general practitioners, in deciding whether migraine prophylaxis in the individual migraine patient is useful or not. The first step was the development of a questionnaire, consisting of 10 items, which was filled in by 132 migraineurs who called on neurologists or headache experts. Independently, the physicians filled in another questionnaire to answer the question of whether they decided to prescribe migraine prophylaxis and if they had, to give their reasons for doing so. Using logistic regression analysis, we identified the three questions which had the most influence on the decision regarding prophylaxis in the data set. As results, we identified the following three questions:

1. Do you suffer from migraine on more than 3 days/month?
2. Do you have to rest in bed while experiencing a migraine attack?
3. Do you have to take medication against migraine on more than 5 days/month?

Validation of this reduced questionnaire is currently ongoing and involves 150 migraine patients of general practitioners.     

Quantitative testing of sympathetic function with laser doppler flowmetry

Objective. The objective of this study was to develop an indirect technique for evaluating dynamic changes in sympathetic function in humans.Methods. We used laser Doppler to monitor sympathetic mediated vasoconstrictive responses (VRs) produced by 3 different provocative stimuli: 4-second inspiratory gasp (IG), ice-water immersion (Ice), and a spring-loaded pin prick (Pin). Skin perfusion on the thenar eminence was continuously monitored in 10 normal subjects (aged 25 to 36 years) using laser Doppler. Ten trials of the 3 stimuli were presented to each subject at 1-minute intervals. We determined the VR, the percent decrease in perfusion produced by each stimulus, and the 2 standard deviation variation in perfusion.Results. No subject found the IG maneuver uncomfortable. In contrast, the Pin and Ice stimuli were reported to be uncomfortable by 8 and 10 subjects, respectively. Five subjects found Pin and Ice stimuli overtly painful. Vasoconstrictive response was 54.1 ± 2.3% (mean ± SEM) with IG, 49.2 ± 2.0% with Ice, and 24.0 ± 1.8% with Pin. Baseline variation was approximately 15% in all trials.Conclusion. Inspiratory gasp vasoconstrictive response (IGVR) is a sensitive indirect technique for evaluating sympathetic efferent function. We observed that the magnitude of the VR elicited by the IG stimuli was similar to that induced by cold water. Unlike the VR induced by Pin or Ice, IGVR is not dependent on noxious input via somatic afferents; therefore, it can be used in patients with diseases that produce a peripheral neuropathy, such as diabetes mellitus. Present uses of this technique and speculation on future uses are presented.     

Erroneous mass spectrometer readings caused by desflurane and sevoflurane

Objective. Medical mass spectrometers are configured to detect and measure specific respiratory and anesthetic gases. Unrecognized gases entering these systems may cause erroneous readings. We determined how the Advantage 1100 (Perkin-Elmer, now Marquette Gas Systems, Milwaukee, WI) and PPG-SARA (PPG Biomedical Systems, Lenexa, KS) systems that were not configured to measure desflurane or sevoflurane respond to increasing concentrations of these new potent volatile anesthetic agents.Methods. Desflurane 0% to 18% in 3% increments or sevoflurane 0% to 7% in 1% increments in 5-L/min oxygen was delivered to the Advantage and PPG-SARA mass spectrometry systems. For each concentration of each agent, the displayed gas analysis readings and uncompensated collector plate voltages were recorded.Results. The Advantage 1100 system read both desflurane and sevoflurane mainly as enflurane and, to a lesser extent, as carbon dioxide and isoflurane. For enflurane(E) readings <9.9%, the approximate relationships are: %Desflurane=1.6E; %Sevoflurane=0.3E. These formulas do not apply if E >9.9% because of saturation of the summation bus. PPG-SARA read desflurane mainly as isoflurane(I) and, to a lesser extent, as nitrous oxide. PPG-SARA read sevoflurane mainly as enflurane(E) and, to a lesser extent, as nitrous oxide and halothane. The approximate relationships are: %Desflurane=1.11 (for I < 9%); %Sevoflurane=2.1E.Conclusions. Advantage 1100 and PPG-SARA systems not configured for desflurane or sevoflurane display erroneous anesthetic agent readings when these new agents are sampled. Advantage 1100 also displays falsely elevated carbon dioxide readings when desflurane is sampled.     

Secondary prevention in acute coronary syndrome patients: a comparison of behavioural medicine and medication randomised controlled interventions

Objective: To compare study quality and clinically meaningful effect sizes in behavioural medicine interventions and medication interventions for post-acute coronary syndrome (ACS) patients. Search strategy: MEDLINE search, supplemented by hand searches of meta-analyses. Selection criteria: All published randomised controlled trials of behavioural medicine interventions for post-ACS patients with mortality as an outcome. One intervention study for each of the eight major medication types randomly selected from meta-analyses of each medication type. Data collection and analysis: Data were independently extracted by two reviewers. The checklist for statistical assessment of randomised controlled trials of the British Medical Journal was applied to evaluate study quality. Clinical significance of effect sizes was estimated using a converted binomial effect size index. Main results: The average study quality of the medication trials was higher, and more reached statistical significance than the behavioural medicine trials. Conclusions: Behavioural medicine interventions need to improve methodological quality, increase power and accumulate sufficient studies within one intervention area so that an evidence-based conclusion about treatment efficacy can be formulated.