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Effects of topical anesthesia on upper airway resistance during wake-sleep transitions.

Deformation of the upper airway (UA) by negative transmural pressure alters the activity of UA mechanoreceptors, causing a reflex increase in UA muscle activity. Topical anesthesia of the UA mucosa, which greatly reduces this reflex response, causes an increase in UA resistance during stage 2 sleep. We hypothesized that topical anesthesia of the UA mucosa would predispose to UA instability at sleep onset and, therefore, examined the effect of UA anesthesia on pharyngeal resistance (Rph) in stage 1 sleep. Eleven normal, healthy volunteers were instrumented to record standard polysomnographic variables, respiratory airflow, and UA pressure at the nasal choanae and the epiglottis. Subjects were permitted to sleep until stable stage 2 sleep was reached and were then awoken. This procedure was repeated three times to obtain reproducible wake-sleep transitions. The UA mucosa was then anesthetized with 10% lidocaine to the oropharynx and laryngopharynx, and the pharyngeal mechanics were studied during the subsequent wake-sleep transition. Three subjects were excluded because of failure to resume sleep postanesthesia. Rph was significantly higher after anesthesia during stage 1 sleep [2.88 +/- 0.77 cmH(2)O.l(-1).s (mean +/- SE)] compared with control (0.95 +/- 0.35 cmH(2)O.l(-1).s; P < 0.05), but there was no difference during wakefulness. Furthermore, there was a significant rise in Rph at wake-to-sleep transitions and a significant fall in Rph at sleep-to-wake transitions after anesthesia (P < 0.05) but not in the control condition. We conclude that sensory receptors in the UA mucosa contribute to the maintenance of UA patency at wake-sleep transition in normal humans.

Administration, Topical↗

Spontaneous and artificial activation of neocortical seizures.

The aim of this study is to disclose the mechanisms underlying the recruitment of neocortical networks during slow-wave sleep oscillations evolving into spike-wave (SW) seizures. 1) We investigated the activation of SW seizures in a seizure-prone neocortex by means of electrical stimuli applied within the frequency range of spontaneous sleep oscillations. Stimuli were grouped in bursts of 10 Hz, similar to sleep spindles, and repeated every 2 s, to reproduce their rhythmic recurrence imposed by the slow (<1 Hz) sleep oscillation. Either cortical or thalamic stimuli, which were applied while the cortex displayed sleeplike activity, gradually induced paroxysmal responses in intracellularly recorded neocortical neurons, which were virtually identical to those of spontaneous seizures and consisted of a progressive buildup of paroxysmal depolarizing shifts (PDSs). 2) The ability of cortical networks to follow stimuli was tested at various stimulation frequencies (1-3 Hz) and quantified by calculating the entropy of the ensuing oscillation. Rhythmic PDSs were optimally induced, and the lowest entropy was generated, at a stimulation frequency around 1.5 Hz. Fast runs at 10-15 Hz, which often override PDSs, thus contributing to the polyspike-wave pattern of seizures, were induced by cortical stimuli, but were disturbed by thalamic stimuli. Spontaneous seizures generally evolved toward an accelerated discharge of PDSs. It is suggested that these accelerating trends during SW seizures act as protective mechanisms by provoking the uncoupling of cortical networks and eventually arresting the seizure.

Animals↗

Mechanisms of adrenomedullin-induced dilatation of cerebral arterioles.

BACKGROUND AND PURPOSE: Adrenomedullin is a recently discovered vasoactive peptide that is structurally related to calcitonin gene-related peptide (CGRP). Adrenomedullin is produced by vascular endothelium and smooth muscle and is present in the brain. The goals of this study were to determine (1) whether adrenomedullin produces dilatation of cerebral arterioles and whether this effect is mediated by activation of CGRP receptors and (2) whether vasodilatation to adrenomedullin was mediated by K+ channels. METHODS: Diameter of cerebral arterioles (mean +/- SE baseline, 46 +/- 1 microns) was measured using a closed cranial window in anesthetized rats. RESULTS: Application of rat adrenomedullin (10(-7) and 10(-6) mol/L) increased vessel diameter by 16 +/- 3% and 45 +/- 8% (n = 5), respectively. Vasodilator responses to repeated application of adrenomedullin were reproducible. Pretreatment of cerebral arterioles with the specific CGRP1 receptor antagonist CGRP-(8-37) (5 x 10(-7) mol/L) selectively inhibited the vasodilator responses to adrenomedullin without inhibiting responses to ADP (10(-5) to 10(-3) mol/L). Responses to adrenomedullin (10(-7) and 10(-6) mol/L) were 14 +/- 1% and 40 +/- 3% before and 2 +/- 2% and 6 +/- 1% after CGRP-(8-37), respectively (P < .01). Glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K+ channels, reduced the responses to adrenomedullin without attenuating responses to ADP. Responses to adrenomedullin were 19 +/- 4% and 35 +/- 6% before and 6 +/- 3% and 19 +/- 5% after glibenclamide, respectively (P < .05). Iberiotoxin (10(-7) mol/L), an inhibitor of calcium-dependent K+ channels, also significantly attenuated responses to adrenomedullin and did not inhibit vasodilatation to papaverine. Responses to adrenomedullin were 16 +/- 2% and 55 +/- 8% before and 12 +/- 4% and 26 +/- 3% after iberiotoxin, respectively (P < .01 for 10(-6) mol/L adrenomedullin). CONCLUSIONS: Adrenomedullin produces substantial dilatation of cerebral arterioles in vivo, and the response is mediated in large part by activation of CGRP1 receptors. Cerebral vasodilatation to adrenomedullin appears to be dependent on activation of K+ channels.

Adenosine Diphosphate↗

Standardization of inhalation provocation tests: two techniques of aerosol generation and inhalation compared.

Comparison of methods of aerosol generation and inhalation is required to improve standardization of inhalation provocation tests. We compared two widely used methods in 10 asthmatics, by measuring the dose and distribution of radiolabeled aerosol deposited in the throat and lung, and the provocation concentration of inhaled histamine required to reduce the FEV1 by 20% (PC20). In one method, aerosol was generated by a DeVilbiss 646 nebulizer attached to a dosimeter, and was inhaled by 5 inspiratory capacity breaths. The measurements with each method were repeated once to determine the reproducibility of results. Both methods deposited the same dose in the lung, but the distribution of the dose was different; the dosimeter method deposited more aerosol in the throat and central airways. The PC20 obtained with each method was the same. The reproducibility of all measurements in the same subject was similar. The lung dose deposited by each method in different subjects varied to the same degree. The results indicated that the bronchial response to inhaled histamine can be measured as reliably using a nebulizer and tidal breathing as by a more complex dose-metering device. They also suggested that, when the methods are regulated as described, the PC20 will have the same clinical significance.

Adolescent↗

Reference values of the provocative concentrations of methacholine that cause 6% and 20% changes in forced expiratory volume in one second in a normal population.

The provocative concentrations of inhaled methacholine that cause 6% (PC6) and 20% (PC20) falls in forced expiratory volume in one second (FEV1) were assessed in a population of 100 nonsmoking persons, equally distributed for sex, who ranged uniformly from 20 to 60 yr of age. These subjects had no respiratory symptoms, rhinitis, atopic history, or familial history of asthma. Single twofold dilutions of methacholine from 2 to 128 mg/ml were used; 81 and 34 subjects, respectively, showed PC6 and PC20 values less than 128 mg/ml. Eight subjects had PC20 values less than 16 mg/ml. In these subjects, the test had a good reproducibility (r = 0.92) when we repeated it, and serial measurements of peak expiratory flow rates did not suggest asthma. The fact that PC6 was related, although loosely, to baseline FEV, FEV/FVC, and forced expiratory flow during the middle half of the FVC (FEF) and that 4 of the 8 subjects with PC20 values less than 16 mg/ml had lower values of FEF might suggest that responsiveness to methacholine is partially linked with baseline airway caliber.

Adult↗

Bone tunnel enlargement after anterior cruciate ligament replacement.

Radiographic increase in the size of tibial and femoral tunnels has been observed. This retrospective study compared tibial tunnel diameter in 56 autograft and 87 allograft patellar tendon bone-tendon-bone anterior cruciate ligament replacements whose observed tunnel changes were correlated with clinical results at 1 year postoperatively. Tibial tunnel sclerotic margins were measured approximately 1 cm below the joint line. Exact tunnel dimension was calculated by using a magnification factor determined by the interference screw of known diameter within the same tunnel. Average allograft tunnel enlargement was 1.2 mm (-2.5 to 6.0) compared with the autograft tunnel enlargement of 0.26 mm (-2.5 to 2.7); the difference was significant (P > 0.0002). No significant difference was seen in KT-1000 arthrometer measurements between autograft or allograft groups, and no correlation was seen between increased tunnel size and clinical outcome as determined by the modified Hughston knee evaluation system. Tunnel measurement reproducibility was confirmed by independent repeated measurements. The significance of this tunnel enlargement is unknown and does not appear to adversely affect clinical outcome of allograft utilization. Possible explanations include an immune response with resorption, stress shielding proximal to the interference screw resulting in resorption, or an inflammatory response by synovium in the tunnel.

Adolescent↗

[Monitoring of adipocyte responsiveness by in situ microdialysis in lipodystrophy tissue: adjustment of a glycerol quantification method in small samples].

In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vivo. In the assessment of physiopathologic alterations seen in lipodystrophy, monitoring of glycerol release is pivotal. Indeed, it allows to quantify the pharmacological responsiveness of subcutaneous adipose tissue in humans. Until now, the small volume of microdialysate collected (5-15 microL/sample) restricted the assessment of glycerol level to the use of the radio-enzymatic method or the reference spectrophotometric microanalysis technique. The aim of this study was to adapt the method of glycerol measurement by iminequinone spectrophotometry colorimetric assay (520 nm) using the following reagent: 0.5 IU Glycerokinase, 1.23 IU glycerophosphate oxidase, 0.98 IU peroxidase, 4.6 mM Mg, 5.4 mM 4-chlorophenol, 0.25 mM 4-aminoantipyrine and 1.4 mM ATP. The assay was setup to run on Olympus AU 2700 automate (15 pL sample volume). The sensitivity of the method was improved by adding a 0.2 mmol triglyceride (TG) solution and 1.5 IU lipase to samples, reducing the limit of free glycerol quantification to 0.020 mmol/L. The analytical repeatability was 2.0% and the reproducibility was 7.9%. The present method thus demonstrated the feasibility of pharmacodynamic exploration of local cutaneous responsiveness in vivo in clinical trials.

Adipocytes↗

Charnley wear model for validation of hip simulators--ball diameter versus polytetrafluoroethylene and polyethylene wear.

Wear rates of polytetrafluoroethylene (PTFE) and polyethylene cups were compared in 9-channel and 12-channel simulators, using serum lubrication and gravimetric techniques for wear assessment. Cobalt-chromium (CoCr) and alumina ceramic femoral heads in 22-42 mm diameter range were used to validate simulator wear rates against clinical data. This was also the first study of three femoral head sizes evaluated concurrently in a simulator (with three replicate specimens) and also the first report in which any wear experiments were repeated. Fluid absorption artefacts were within +/-1 per cent of wear magnitude for PTFE and +/-8 per cent for polyethylene and were corrected for. Wear rates were linear as a function of test duration. Precision within each set of three cups was within +/-6 per cent. The wear rates from experiments repeated over 15 months were reproducible to within +/-24 per cent. However, the magnitudes of the simulator wear rates were not clinically accurate, the PTFE wear rates (2843 mm3/10(6) cycles; 22 mm diameter) were over three times higher than in vivo, the polyethylene 30 to 50 per cent on the low side (23 mm3/10(6) cycles; 22 mm diameter). Volumetric wear rate increased with respect to size of femoral head and a linearly increasing relationship of 7 8 per cent/mm was evident with respect to femoral head diameter for both PTFE and polyethylene. These data compared well with the clinical data.

Aluminum Oxide↗

Application of computer-aided image interpretation to the diagnosis of periapical bone lesions.

An image analysis system was developed for the computer-aided diagnosis of periapical bone lesions in dental radiographs. The system was designed to (1) identify the periapical region, (2) determine the presence of a periapical lesion and (3) estimate the size of the lesion in cases when a lesion had been found. To initiate the procedure, an observer indicates an arbitrary point on the root in a digitized radiograph. From this initial point, the location of the radiographic projection of the apex of the root is automatically computed. Next, the trabecular bone pattern is detected through texture analysis. A local absence of the trabecular bone pattern in the periapical region is marked as a periapical bone lesion. When a lesion has been identified, its size is estimated based on local edge properties. Observer interaction is only allowed to adjust the result of the apex localization procedure if the apex has not correctly been localized. In an experiment with randomly selected radiographs of 111 mandibular roots, the performance of the system was tested against the consensual diagnosis of four expert observers. The sensitivity of the system to identify a lesion was 83.3%, the specificity 75.6% and the diagnostic accuracy 80.2%. The correlation between the size of the lesions as estimated by the system and by the observers was 0.67 (P < 0.01). When the procedure was repeated, the percentage of correctly reproduced lesion sizes by the system was 92.8%. The determination of the presence of a lesion was reproducible in 98.2% of all the cases.

Alveolar Bone Loss↗

Dosimetry of 3 CBCT devices for oral and maxillofacial radiology: CB Mercuray, NewTom 3G and i-CAT.

OBJECTIVES: Cone beam computed tomography (CBCT), which provides a lower dose, lower cost alternative to conventional CT, is being used with increasing frequency in the practice of oral and maxillofacial radiology. This study provides comparative measurements of effective dose for three commercially available, large (12'') field-of-view (FOV), CBCT units: CB Mercuray, NewTom 3G and i-CAT. METHODS: Thermoluminescent dosemeters (TLDs) were placed at 24 sites throughout the layers of the head and neck of a tissue-equivalent human skull RANDO phantom. Depending on availability, the 12'' FOV and smaller FOV scanning modes were used with similar phantom positioning geometry for each CBCT unit. Radiation weighted doses to individual organs were summed using 1990 (E(1990)) and proposed 2005 (E(2005 draft)) ICRP tissue weighting factors to calculate two measures of whole-body effective dose. Dose as a multiple of a representative panoramic radiography dose was also calculated. RESULTS: For repeated runs dosimetry was generally reproducible within 2.5%. Calculated doses in microSv [corrected] (E(1990), E(2005 draft)) were NewTom3G (45, 59), i-CAT (135, 193) and CB Mercuray (477, 558). These are 4 to 42 times greater than comparable panoramic examination doses (6.3 microSv [corrected] 13.3 mSv). Reductions in dose were seen with reduction in field size and mA and kV technique factors. CONCLUSIONS: CBCT dose varies substantially depending on the device, FOV and selected technique factors. Effective dose detriment is several to many times higher than conventional panoramic imaging and an order of magnitude or more less than reported doses for conventional CT.

Humans↗

Two-fold interindividual variation in plasma protein binding of phenytoin in patients with epilepsy.

Plasma protein binding of phenytoin (diphenylhydantoin) in 63 epileptic patients was investigated with an ultrafiltration technique at room temperature using 14C-labelled phenytoin. A strong correlation was found between the total and the unbound drug concentration (r = 0.97, p less than 0.001). The unbound phenytoin fraction was 7.1 +/- 1.0% with a range of 4.9 to 10.2%. This variation is considerably less than that reported recently by different authors. Individual phenytoin binding was reproducible when the determination was repeated several weeks later. Salivary phenytoin concentrations in 33 epileptic patients were significantly correlated to the unbound (r = 0.83) and total concentrations (r = 0.82) of phenytoin in plasma. This study confirms that the clinical practice of monitoring total phenytoin plasma concentrations is sufficient, since the unbound phenytoin fraction has only a 2-fold interindividual variation in epileptic patients, provided that they do not suffer from renal or hepatic disease.

Adult↗

Quantitative determination of islet cell surface antibodies using 125I-protein A.

A quantitative method to measure islet cell surface antibodies in human patients has been developed using 125I-protein A. Isolated, dispersed, viable rat islet cells prepared by collagenase digestion were fixed in 4% paraformaldehyde to allow storage for up to 7 wk at 4 degrees C. Human sera, heat inactivated and adsorbed with rat liver and kidney powder (100 mg/ml), were incubated with the fixed cells (50 x 10(3)) for 60 min at 37 degrees C. Thereafter the cells were washed and exposed to 5 x 10(5) cpm 125I-protein A, which binds to IgG attached to the cell surface. Assay precision (14%) and reproducibility (16%) were established by repeated analysis of pooled sera from healthy individuals and IDDM patients using pooled batches of islet cells. Using this method, islet cell surface antibodies were detected in 35% of insulin-dependent diabetic patients.

Adult↗

A finger volume-oscillometric device for monitoring ambulatory blood pressure: laboratory and clinical evaluations.

A new portable device for the indirect measurement of ambulatory blood pressure in the finger was successfully applied to normotensive and hypertensive subjects in and outside a ward setting. The device uses the volume-oscillometric technique and, equipped with a microprocessor, permits long-term ambulatory monitoring of indirect systolic and mean blood pressure at desired intervals (once every 1-10 min). Systolic and mean blood pressures obtained by this method were well correlated with those measured by the direct (Oxford) and arm-cuff methods. Systolic and diastolic blood pressure obtained by the volume-oscillometric device were almost identical with those recorded by an arm-cuff. Systolic blood pressure obtained by the volume oscillometric method was, however, significantly lower than that measured by the direct method. The new device has also been used to measure blood pressure during treadmill exercise and ice-water immersion. Mean values of blood pressure and the SD of these averaged for 24 hours, or for every hour, were reproducible when the measurements were repeated under the same condition. The present device is portable, causes minimal noise, can detect rapid change in blood pressure and causes less discomfort when compared to the conventional arm-cuff method. Regular measurements can be made with minimal sleep disturbance. This fully automatic volume-oscillometric device allows reliable 24-hour monitoring of ambulatory blood pressure not only in but also outside a ward setting, and as such is useful for studies of hypertension.

Ambulatory Care↗

Comparison of ion-specific electrode and high performance liquid chromatography methods for the determination of iodide in milk.

Two methods for the determination of I- in raw and processed milk were examined. A simple ion-specific electrode (ISE) method was compared against a more complex HPLC reference technique. Accuracy and precision were evaluated both within and between the 2 methods. Both methods yielded good recoveries for Ion spiked samples, ranging from 87 to 114% for ISE and 91 to 100% for HPLC. Within-run repeatability and between-run reproducibility were superior with the HPLC method, but were still more than acceptable with the ISE technique. Overall agreement of paired results between ISE and HPLC methods was good (r2 = 0.85 on raw herd milk; r2 = 0.84 on processed milk). The ISE method had a significant positive bias relative to the HPLC reference method. Both methods lend themselves well to the measurement of I- in raw or processed milk. Given its relatively low cost and ease of use, the ISE method is well suited as a screening method. The impressive accuracy, precision, selectivity, and limit of detection of the HPLC technique make it an ideal confirmation method.

Animals↗

Distortions and fluctuations in topographic memory.

Two experiments dealing with the learning of a space by map or by navigation approached the questions of equivalency of the cognitive processes involved in spatial information and of response fluctuation. In the first experiment, 11 subjects were asked to situate, six times, 18 locations on a blank map. In the second experiment, the subjects were first given 3 min to learn a map with 12 locations marked, and then asked to reproduce it. The task was repeated six times, using three different maps. This gave us several trials per subject, so that distortion could be distinguished from response fluctuation. In Experiment 1, the range of values was the same for response inaccuracy and response fluctuation; in Experiment 2, the range was greater for response inaccuracy than for response fluctuation. The results showed that space learning by navigation and space learning by map involve different cognitive processes.

Adult↗

Comparison of bone mass in forearm, lumbar vertebra and hip by single and/or dual energy X-ray absorptiometry.

OBJECTIVE: Bone mineral density (BMD) was measured in normal Chinese women with single X-ray absorptiometry (SXA) and dual energy X-ray absorptiometry (DEXA). These two methods were compared to evaluate the sensitivity in reflecting bone loss. METHODS: Measurements were performed in 300 women aged 20 to approximately 79 (5 for each age). The 8mm distal, 1/4 distal, ultra distal site of the nondominant forearm were measured with SXA; the AP spine (L2-4), right femoral neck (Neck), Ward's triangle (Ward) and trochantor (Troch) were measured with DEXA. Ten women had 5 repeated measurements to evaluate the reproducibility of the equipments. RESULTS: The BMD peak for Neck and Ward was found between age 20 to approximately 29, for ultra distal and L2-4 at age 30 to approximately 39, for 8mm distal, 1/4 distal and Troch at age 40 to approximately 49. After reaching the peak values, BMD at all sites decreased with increasing age. The highest rate of yearly loss of BMD was at 8mm distal. Results of measurement showed significant correlation between SXA and DEXA. Comparing with premenopausal women, the bone loss rate in postmenopausal women was faster and highest up to 11 to approximately 15 years and the highest rate was at the Ward. CONCLUSION: The present study gives the normal values of BMD at seven sites for normal Chinese women. The ages of BMD peak were different at seven sites. The yearly loss of BMD was highest at 8mm distal, it seemed to be the sensitive region for bone loss with age. The postmenopausal women had highly significantly loss bone mass than the premenopausal women. Comparing with premenopause, postmenopause BMD for Ward's triangle with DEXA seemed to be most sensitive to the effect of menopause.

Absorptiometry, Photon↗

Comparison of Frank's and McFee's lead systems using multivariate statistics.

Two widely used orthogonal corrected 3-lead system - the Frank and the McFee systems - were studied in order to evaluate whether a significant difference in diagnostic performance could be observed; in the case of a positive answer, we would be able to advocate one system instead of the other. No such overall difference was noticed. Although +/- 17% discrepancies were found on the individual classification level (a patient correctly classified with system A and missed with system B and conversely), the practical implication is negligible since each system is responsible for +/- half of these discrepancies. Multivariate analysis, as already largely proved by Pipberger's group, drastically ameliorates the diagnostic results. Special caution has been given to the number of selected discriminators in order to enhance repeatability of the results; the reproducibility, using the approach developed by Cornfield, was found excellent. Some particular features as to the choice and location of the best discriminators were found somewhat puzzling by the autors but no deterministic explanation could be offered: the selection of the variables, indeed, rested on statistical bases and not on the (sometimes fragmentary) knowledge of what is going on in the heart and how these events relate to surface waveform patterns.

Adult↗

Quantitative determination of chloramphenicol in milk powders by isotope dilution liquid chromatography coupled to tandem mass spectrometry.

A method is described for the determination of residues of the illegal antibiotic chloramphenicol (CAP) in milk powders. The analyte is quantified by liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (LC-ESI-MS-MS) operating in negative ion multiple reaction monitoring mode (MRM) after a liquid-liquid extraction followed by a clean-up step on solid phase extraction (SPE) cartridge. Because of the presence of two chlorine atoms in the CAP molecule, four specific transition reactions of CAP were monitored by MS-MS in selecting m/z 321 --> 257, 321 --> 152 (35Cl2) and m/z 323 --> 257, 323 --> 152 (37Cl35Cl). Two calibration curves were constructed by plotting the area ratio of m/z 321 --> 152 versus 326 --> 157 and m/z 321 --> 257 versus 326 --> 262 against their corresponding amount ratio. Indeed, even if m/z 321 --> 152 was found to give a higher MS-MS response (calibration curve used by default), an interfering chemical substance was sometimes observed for some milk extracts and not for the transition m/z 321 --> 257. The quantitation method was validated according to the European Union (EU) criteria for the analysis of veterinary drug residues at 0.1, 0.2 and 0.5 microg/kg concentration levels using d5-CAP as internal standard. The decision limit (CCalpha) and detection capability (CCbeta) of CAP in milk were calculated for m/z 321 --> 152 at 0.02 microg/kg and 0.03 microg/kg, respectively, and for m/z 321 --> 257 at 0.02 microg/kg and 0.04 microg/kg, respectively. At the lowest fortification level (i.e. 0.1 microg/kg), repeatability and within-laboratory reproducibility were calculated for m/z 321 --> 257 both at 0.02 microg/kg and for m/z 321 --> 152 at 0.03 and 0.05 microg/kg, respectively. Moreover, the measurement of uncertainty of the analytical method was calculated at the same spiking levels and falls within the precision values of the within-laboratory reproducibility. This method can be applied to several types of milk powders (e.g. full cream, skim) and can serve as a monitoring tool to avoid that unacceptable levels of residues of CAP enter the food chain.

Animals↗