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Biomedical subjects

G Musch

Publications and source records attributed to G Musch.

16 recordsLinked to original sources

Positron emission tomography imaging of regional lung function.

Regional pulmonary perfusion and ventilation can be assessed by imaging, with positron emission tomography (PET), the pulmonary kinetics of [13N]nitrogen (13N2). Because of its low solubility in blood and tissues, 13N2 infused intravenously in saline solution evolves into the alveolar airspace at first pass, where it accumulates in proportion to regional perfusion during a short apnea. In contrast, infused 13N2 is not retained in non-aerated regions, which do not exchange gas. Robust estimates of regional perfusion and shunt are obtained by modeling the pulmonary kinetics of 13N2 infused as a bolus during a short apnea. Regional ventilation is measured by modeling the washout of 13N2 after breathing is resumed. Regional gas content and dead space ventilation can be measured with inhalation of 13N2. Application of this novel functional imaging technique can further the understanding of the pathophysiology of a variety of pulmonary processes. This review briefly describes the methodological aspects of PET imaging of regional perfusion and ventilation and then focuses on insights in the pathophysiology of acute lung injury and asthma that have been gained by imaging the pulmonary kinetics of 13N2 with PET.

Humans↗

Modeling kinetics of infused 13NN-saline in acute lung injury.

A mathematical model was developed to estimate right-to-left shunt (Fs) and the volume of distribution of 13NN in alveolar gas (VA) and shunt tissue (Vs). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes 13NN kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of 13NN-labeled saline was injected at the onset of apnea as PET imaging and arterial 13NN sampling were initiated. The model fit the tracer kinetics well (mean r2 = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. Fs derived from the model correlated well with shunt estimates derived from O2 blood concentrations and from PET images. Fs was higher for LS (54 +/- 18%) than for LP (5 +/- 4%) and NP (1 +/- 1%, P < 0.01). VA, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 +/- 0.09) than for LP (0.96 +/- 0.28, P < 0.01), whereas Vs, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 +/- 0.26) than for LP (0.05 +/- 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial 13NN kinetics and provides estimates of Fs, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position.

Algorithms↗

Reverse-thrust ventilation in hypercapnic patients with acute respiratory distress syndrome. Acute physiological effects.

Techniques of tracheal gas insufflation (TGI) have been shown to enhance CO(2) clearance efficiency in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Clinical studies have explored the effects of such techniques only at moderate intratracheal gas flow rates, with TGI superimposed to mechanical ventilation in a continuous fashion, or synchronized to the expiratory phase of the duty cycle. We examined the effects of intratracheal pulmonary ventilation (ITPV), delivering the entire tidal volume (VT) in the proximity of the tracheal carina, with all the gas flow supplied continuously through a reverse-thrust catheter (RTC). A potential limitation in the application of TGI is dynamic hyperinflation. Therefore, in a subgroup of patients, we also evaluated the effects of ITPV on end-expiratory lung volume (EELV) by respiratory inductive plethysmography (RIP). Eleven patients with ARDS under volume-cycled mechanical ventilation were subsequently switched to ITPV at the same baseline respiratory rate, I:E ratio, and VT. At the same minute volume, Pa(CO(2)) decreased from 70 +/- 12.3 to 59 +/- 9.5 mm Hg, with a percent reduction of 15 +/- 4% (range from 10 to 20%). The CO(2) decrease was greater in patients with higher baseline Pa(CO(2)) levels (DeltaPa(CO(2)) = 0.29 x Pa(CO(2)) - 9.48, r = 0.95). During transition from mechanical ventilation to ITPV, tracheal positive end-expiratory pressure (PEEP(tr)) decreased with a correspondent decrease in EELV. Both were restored by increasing the PEEP at the ventilator by 3.6 +/- 2.0 cm H(2)O. These data suggest that in patients with ARDS ITPV effectively reduces dead space ventilation and the employment of the RTC may limit or avoid dynamic hyperinflation.

Adult↗

Dysphagia following intrathecal local anesthetic-opioid administration.

We describe the case of a parturient who developed dysphagia shortly after the intrathecal injection of a local anesthetic-opioid combination for cesarean section. Dysphagia was the only symptom of cephalad spread of the spinal anesthetic, and it was not associated with a "high" motor or sensory block. Although it resolved spontaneously, the dysphagia was extremely distressing to the patient. We conclude that dysphagia, even in the absence of an overtly "high spinal," should be added to the possible side effects of intrathecal local anesthetic-opioid administration in parturients.

Adult↗

The resonant step frequency in human running.

At running speeds less than about 13 km h-1 the freely chosen step frequency (ffree) is lower than the frequency at which the mechanical power is minimized (fmin). This dissociation between ffree and fmin was investigated by measuring mechanical power, metabolic energy expenditure and apparent natural frequency of the body's bouncing system (fsist) during running at three given speeds with different step frequencies. The ffree requires a mechanical power greater than that at fmin mainly due to a larger vertical oscillation of the body at each step. Energy expenditure is minimal and the mechanical efficiency is maximal at ffree. At a given speed, an increase in step frequency above ffree results in an increase in energy expenditure despite a decrease in mechanical power. On the other hand, a decrease in step frequency below ffree results in a larger increase in energy expenditure associated with an increase in mechanical power. When the step frequency is forced to values above or below ffree, fsist is forced to change similarly by adjusting the stiffness of the bouncing system. However the best match between fsist and step frequency takes place only in proximity of ffree (2. 6-2.8 Hz). It is concluded that during running at speeds less than 13 km h-1 energy is saved by tuning step frequency to fsist, even if this requires a mechanical power larger than necessary.

Adult↗

Lung and chest wall mechanics in normal anaesthetized subjects and in patients with COPD at different PEEP levels.

In order to assess the relative contribution of the lung and the chest wall to the derangements of respiratory mechanics in chronic obstructive pulmonary disease (COPD) patients with acute ventilatory failure (AVF), we studied eight COPD patients undergoing controlled mechanical ventilation for AVF and nine normal subjects anaesthetized for surgery as a control group. With the use of the interrupter technique together with the oesophageal balloon technique we measured: static lung and chest wall elastances (E[st,L] and E[st,w], respectively), maximum (R[L,max]), minimum (R[L,min]) and additional (deltaR[L]) lung resistances, additional chest wall resistance (deltaRw) and, in the COPD group, total intrinsic positive end-expiratory pressure (PEEPtot). Measurements were repeated at 0, 5, 10 and 15 cmH2O of applied positive end-expiratory pressure (PEEP). We found that, in the COPD group: 1) both E(st,w) and deltaRw were higher than in the normal group; 2) R(L,max) was markedly increased due to an increase of both R(L,min) and deltaRL; 3) even low levels of PEEP increased PEEPtot; 4) PEEP did not reduce elastance or total resistance of either the lung or the chest wall. We conclude that chest wall mechanics are abnormal in chronic obstructive pulmonary disease patients with acute ventilatory failure undergoing controlled mechanical ventilation and that positive end-expiratory pressure does not seem to be effective in reducing either elastance or resistance of the lung or chest wall.

Anesthesia, General↗

Positive end-expiratory pressure prevents the loss of respiratory compliance during low tidal volume ventilation in acute lung injury patients.

STUDY OBJECTIVE: To study the effect of positive end-expiratory pressure (PEEP) on the decay of respiratory system compliance (Cpl,rs) due to low tidal volume (VT) ventilation in acute lung injury (ALI) patients. SETTING: General ICU in a university hospital. PARTICIPANTS: Eight ALI patients with a lung injury score greater than 2.5. INTERVENTION: Pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV), with an average VT of 8.5 +/- 0.4 mL/kg, were applied at three levels of PEEP (5, 10, and 15 cm H2O). Before each PCV and VCV period, lung volume history was standardized by manual hyperinflation maneuvers. MEASUREMENTS: We measured Cpl,rs at time 0 (start), 10, 20, and 30 (end) min from the beginning of each PCV and VCV period. Gas exchange and hemodynamic data were collected at end. RESULTS: At PEEP 5 and 10 cm H2O, we observed a progressive Cpl,rs decay with both PCV and VCV modes. At PEEP 5 cm H2O, we detected a higher Cpl,rs decrease during PCV, due to a higher Cpl,rs at start, compared with VCV. At PEEP 15 cm H2O, Cpl,rs did not decrease significantly. Cpl,rs values measured at end as well as oxygenation and hemodynamic data did not differ between PCV and VCV. At PEEP 15 cm H2O, PCV provided lower PaCO2 than VCV. CONCLUSIONS: A PEEP of at least 15 cm H2O was needed to prevent Cpl,rs decay. The progressive Cpl,rs loss we observed at lower PEEP probably reflects alveolar instability.

Adult↗

Small pore size microporous membrane oxygenator reduces plasma leakage during prolonged extracorporeal circulation: a case report.

Plasma leakage has been regarded as the main technical problem during prolonged extracorporeal circulation (ECC) with microporous membrane oxygenators (MMOs). We report the case of a 15 year old male who underwent long term ECC for ARDS and in whom, by using new MMOs with reduced pore size, we were able to achieve prolonged artificial gas exchange efficiency with minimal plasma leakage. We conclude that reduced pore size MMOs might represent a valuable technical advance in extracorporeal oxygenation therapy.

Adolescent↗

Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers.

1. The influence of a single oral dose of nicardipine 30 mg on the pharmacokinetics and pharmacodynamics of propranolol 80 mg was investigated in twelve healthy volunteers. 2. Co-administration of nicardipine significantly increased the AUC and the mean Cmax of propranolol. 3. Blood pressure and heart rate tended to decrease more when propranolol and nicardipine were administered together than when propranolol was given alone, but differences are of doubtful significance. 4. The results indicate that nicardipine alters the pharmacokinetics of propranolol by impaired hepatic 'first-pass' clearance, but pharmacodynamics were little affected.

Adult↗

Determination of pentoxifylline and its 5-hydroxy metabolite in human plasma by solid-phase extraction and high-performance liquid chromatography with ultraviolet detection.

The simultaneous determination of pentoxifylline and its 5-hydroxy metabolite in human plasma was performed: 10 ng/ml pentoxifylline and 15 ng/ml metabolite were determined at a signal-to-noise ratio of 3. The recoveries from plasma at a 100 ng/ml level were 98.0 and 86.9% for pentoxifylline and the metabolite, respectively. The intra- and inter-assay coefficients of variation were less than 5% for both pentoxifylline and the metabolite. This method shows advantages over many other published extraction procedures prior to high-performance liquid chromatographic analysis in terms of its speed and ease of manipulation.

Adult↗

A strategy for the determination of beta blockers in plasma using solid-phase extraction in combination with high-performance liquid chromatography.

This paper describes a general approach for the therapeutic drug monitoring of 13 different beta blockers in plasma. The chromatographic system contains a cyanopropyl-bonded phase as a stationary phase in combination with a mobile phase composed of acetonitrile and phosphate buffer (pH = 3, mu = 0.05). Two modes of detection are used, namely, UV detection and fluorescence detection. The sample pretreatment is performed with a nitrile-sorbent in combination with methanol-phosphate buffer (pH = 3, mu = 0.05) or with methanol containing 0.1% propylamine as eluent. Acceptable recoveries are obtained for practolol, acebutolol, pindolol, oxprenolol, mepindolol, atenolol, propranolol, prenalterol, alprenolol, metoprolol, sotalol and nadolol. For labetalol, however, the elution recovery has to be improved. Finally, this approach is illustrated by the assay of nadolol in the plasma of patients suffering from hypertension, who had received an oral formulation of the drug.

Adrenergic beta-Antagonists↗

Isolation of basic drugs from plasma using solid-phase extraction with a cyanopropyl-bonded phase.

The use of a CN sorbent for the isolation of basic compounds from plasma is described. Adsorption from water and plasma was investigated for a test set of 30 basic drugs. It was found that compounds with a carbon chain length greater than or equal to 11 are totally retained and that the competitive effect of the matrix on the adsorption is minimal. Methanol-phosphate buffer (pH 3, mu = 0.05) (50:50) yielded good recoveries for more polar compounds; apolar basic drugs can be efficiently eluted using methanol containing 0.1% propylamine. Water up to 3 ml can be used for the washing step. This approach was applied to the determination of eight drugs in plasma at therapeutic levels. The absolute recoveries (n = 6) obtained were 98.8 +/- 7.3% for papaverine, 82.3 +/- 3.9% for practolol, 83.4 +/- 2.6% for metoclopramide, 87.3 +/- 5.8% for imipramine, 82.8 +/- 3.3% for procaine, 82.7 +/- 4.6% for morphine, 87.5 +/- 7.2% for propranolol and 90.4 +/- 6.2% for yohimbine.

Adsorption↗

Feasibility study concerning the use of expert systems for the development of procedures in pharmaceutical analysis.

The feasibility of using expert systems for the development of analytical procedures is investigated. A system for the computer generation of procedures to determine active drug substances in commercial formulations is proposed. It is shown that in nearly 85% of the cases investigated the present system immediately yields a correct procedure or conclusion. It is concluded that selecting methods and developing procedures with the use of expert systems is difficult but feasible.

Journal Article↗

Expert system for pharmaceutical analysis. I. Selection of the detection system in high-performance liquid chromatographic analysis: UV versus amperometric detection.

The usefulness of amperometric detection in pharmaceutical analyses was investigated for different groups of drugs. The UV response at 254 nm and that at the absorption maximum of the solute were compared with the electrochemical signal obtained. The minimum detectable concentration (nanograms on-column) of each substance is reported for the three different detection systems. This comparison was performed for 72 drugs (local anaesthetics, antipyretics, tricyclic antidepressants, sulphonamides, sex hormones, beta-adrenoceptor blocking agents, phenothiazines, alkaloids, diuretics and penicillins). The median limit of detection of the amperometric detector (see definition in the text) is 1.0 ng on-column and the median gain in sensitivity, compared with UV detection is 22.5.

Adrenergic beta-Antagonists↗

Determination of benzalkonium chloride in drug formulations by capillary electrophoresis (CE).

A Capillary Electrophoresis method was developed and applied successfully to test the quality of different drug formulations for release and stability studies. In the method an uncoated fused-silica capillary was employed containing a phosphoric acid buffer electrolyte which was brought to pH by triethylamine. The benzalkonium chlorides (BAC-C12 and BAC-C14) present in the standard were completely separated from each other and from the peaks of the main compound. Performance results of the method in terms of system repeatability, precision and accuracy are discussed.

Benzalkonium Compounds↗