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Biomedical subjects

G W Sybrecht

Publications and source records attributed to G W Sybrecht.

At least 109 records · Page 6Linked to original sources

Determination of theophylline in saliva, using fluorescence polarization immunoassay (FPIA).

Theophylline concentrations were determined by fluorescence polarization immunoassay (FPIA) in saliva, serum and serum water of healthy volunteers and outpatients after administration of single theophylline doses, and after the administration of several doses in order to establish a steady state. The FPIA allowed rapid and reliable theophylline determinations in saliva and serum water (between-days coefficients of variation: less than 3%; recovery: 95-03%). Salivary theophylline concentrations measured by FPIA in 30 samples agreed well with those determined by HPLC. Furthermore the results obtained by ultrafiltration for the concentration of unbound theophylline in serum water were in good agreement with those determined by ultracentrifugation. The binding of theophylline by serum protein rose by about 25%, when the pH of the samples was increased from 7.0 to 8.0. After adjusting the pH to 7.4, average values for theophylline binding to proteins at 25 degrees C ranged from 48.5 to 52.2% in serum samples from outpatients and healthy adults. Salivary theophylline concentrations correlated well with total and free serum theophylline concentrations in healthy adults and outpatients (r = 0.90-0.98). The theophylline concentration in saliva was on average about 20-30% higher than the unbound theophylline concentration in serum water. The saliva/serum concentration ratio of theophylline showed some intersubject variation (0.68 +/- 0.08; range: 0.50-0.85). Using the mean saliva/serum concentration ratio of the patient group, steady state serum theophylline concentrations were predicted from salivary levels with a mean error of 7.6% (range: 0.0-26.8%). The salivary theophylline concentration appears to be a suitable parameter for assessment of compliance, for identification of patients with inappropriate dosage, and for consequent dosage adjustment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nocturnal asthma: effect of a once per evening dose of sustained release theophylline.

In a double-blind, multiple-dose, cross-over study the therapeutic effects of an S-R theophylline preparation given once each night (mean 11.2 mg/kg/day) were compared to standard treatment with an S-R aminophylline preparation every 12 h (mean 10.3 mg theophylline/kg/day) in 9 patients with nocturnal asthma. On Day 5 of each treatment period, serum theophylline concentrations and PEF were measured every 2 h over a 24 h period. With the twice-daily regimen peak theophylline concentrations were lower at night than during the day (mean 9.4 +/- 0.9 vs 11.3 +/- 1.0 mg/1). With the single administration, serum theophylline concentrations were considerably higher at night (mean C max 16.3 +/- 1.4 mg/1). In spite of the high theophylline peak to trough difference (mean 12.0 +/- 2.1 mg/1) during the once daily regimen, the circadian variations of PEF were significantly reduced. Thus, greater airways' stability can be obtained by appropriate timing of theophylline administration.

Adult↗

Individualizing theophylline dosage: evaluation of a single-point maintenance dose prediction method.

A dosage prediction method to estimate theophylline clearance and dose requirement was evaluated in 22 outpatients with partly reversible obstructive airways disease. The steady state theophylline dose required to achieve a target concentration (Css) was predicted using a single serum theophylline determination 8 h after a single oral test dose. In 17 nonsmoking patients a mean absolute deviation of 8.2% (range 0.0-21.7%) between predicted and observed Css was found, and in 5 smoking patients the mean deviation was 34.0% (range 2.2-53.8%). In 17 healthy smokers the single-point method was found to predict theophylline clearance at a sampling time of 8 h with a prediction error of 11.3 (range 0.8-25.3%) compared to the clearance determination using the area under the curve. In addition, a numerical simulation program to assess the influence of absorption, elimination and sampling time on predictive accuracy showed that the method could be successfully applied to a patient population with elimination rate constants between 0.07 1/h and 0.25 1/h, allowing a mean prediction error of 15%.

Adolescent↗

Influence of brotizolam on the ventilatory and mouth-occlusion pressure response to hypercapnia in patients with chronic obstructive pulmonary disease.

Effect of 0.25 mg brotizolam on patients with chronic obstructive lung disease of moderate to severe degree was studied. There was no difference between the slopes of ventilation vs alveolar CO2 for brotizolam and placebo as compared with base line values. Mouth-occlusion pressures did not change under the influence of drug or placebo. Brotizolam (0.25 mg) is without adverse side-effects on respiratory centre output or on mechanics of ventilation.

Adult↗

[Peridural morphine-analgesia. II. Respiratory depression (author's transl)].

In nine healthy young patients ventilatory CO2-response curves and mouth-occlusion pressure were measured after peridural injection of 5 mg morphine hydrochloride diluted in 10 ml saline solution in the lumbar region. Patients were not premedicated. Prior to measurements lower extremity operations were performed under peridural anaesthesia. Five minutes after peridural morphine injection there was a slight reduction in ventilatory response to increasing CO2 (94.7% +!- 15%), which was even more pronounced one hour later (74.5% +/- 14.7%). Mouth occlusion pressure decreased to 86.7% +/- 27.4% after 5 min to 72.4% +/- 13.4% after 60 min. Changes in the relation of the central stimulus P100 to the resulting flow (VT/Ti) was 96.7% +/- 32.5% after 5 min and 95.0% +/- 31.4% after 60 min. These results demonstrate a central respiratory depression after peridural morphine injection with a consequent reduction in ventilatory CO2-response.

Adult↗

[Lung function, gas exchange and regulation of ventilation in patients with portocaval encephalopathy (author's transl)].

In 17 patients, breathing room air and pure oxygen, with histologically proven cirrhosis of the liver and portocaval encephalopathy grade I, static and dynamic lung volumes, closing capacity and arterial blood gases were determined. Furthermore, CO2, response curves were provided and mouth occlusion pressure measurements were carried out. The residual volume was found to be increased (130 +/- 8% of predicted) which resulted in decreased vital capacity (79 +/- 2% of predicted) with total lung capacity being normal (94 +/- 2% of predicted). Closing capacity was increased to 134 +/- 5% of the predicted value. Gas exchange for oxygen was impaired (AaDO2 = 262 +/- 30% of predicted). Arterial PO2, however, was within normal range PaO2 = 84 +/- 3.6 mm Hg) due to hyperventilation (PaCO2 = 28.1 +/- 0.8 mm Hg). Hypoxic ventilatory stimulation could be excluded because inspiration of pure oxygen caused no change of PaCO2 (PaCO2 = 27.3 + 0.7 mm Hg and PaO2 = 465 + 16.9 mm Hg with FIO2 = 1.0). The slope of the CO2 response curves was normal, the mouth occlusion pressures, however, were higher than the predicted value: up to PaCO2 of 55 mm Hg. The slope of these curves being smaller than predicted. The results show that in patients with portocaval encephalopathy the lung function is disturbed due to premature airway closure with consequently decreased regional ventilation: perfusion ratios and that regulation of ventilation is impaired by a loss of sensitivity for CO2 with high basal output of the respiratory centers not related to CO2.

Blood Gas Analysis↗

[Effect of potent analgesics on the ventilatory CO2 response and on the mouth occlusion pressure (author's transl)].

The depressant effects of four potent analgesics on the respiration were studied in 9 healthy young persons by determining the CO2 response (Read's method) and the mouth occlusion pressure (Whitelaw's method) before and after administration of the drugs and with or without interposition of additional inspiratory resistance (Rin). The analgesics tested were: Mr. 1268 = M1; pentazocine = M2; tramadol = M3; Mr. 1353 = M4. M1 and M2 induced a marked reduction in the ventilatory CO2 response (56.2 per cent +/- 21.8 for M1 and 53.8 per cent +/- 17.1 for M2). Interposition of Rin reduced the response to 43.9 per cent +/- 15.5 and 41.7 per cent +/- 17.3 respectively of the normal value. The occlusion pressure fell to 54.3 +/- 17 and 49.4 per cent +!- 22.2 respectively. After interposition of Rin the values were reduced 89 per cent +/- 27.3 and 79.9 +/- 29 respectively from the original value of 152.2 +!- 34.6. Administration of M3 or M4 did not significantly affect either the CO2 response or the occlusion pressure, nor had interposition of Rin any effect. M1 and M2 also induced changes in the ratio central stimulus P100/resultant flow (VT/Ti), viz.: M1 +/- SD: 77.1 per cent +/- 7.1; M2 +/- SD: 77.3 +/- 14.1. M3 and M4 had no significant effect M3 = 92.3 per cent +/- 9.1; M4 = 93.9 per cent +/- 13.3). The data indicate that the two methods make it possible to quantify that the two methods make it possible to quantify the respiratory depression induced by drugs and to differentiate between central respiratory depression and additional impairment of respiratory mechanics.

Adult↗

Monitoring of serum theophylline concentrations by a fully mechanized enzyme immunoassay (EMIT).

An evaluation of an enzyme immunoassay for the determination of theophylline in serum (EMIT, Syva Corp.) is presented. The EMIT assay was fully mechanized by the use of an Eppendorf analyzer 5010. The precision of this enzyme immunoassay was satisfactory (coefficients of variation from day to day ranged from 5--6%). The EMIT assay proved to be specific, rapid and easy to perform. A comparison of the results obtained by EMIT and ultraviolet spectrophotometry in a series of 100 patients showed a good correlation between both methods.

Cross Reactions↗

[The chest roentgenogram during artificial respiration (author's transl)].

Chest roentgenography of artificially ventilated persons not only reveals morphological changes in the lungs but may also provide information regarding their pathogenesis and prognosis. To safeguard against misinterpretation of the findings they should be supplemented by blood gas analyses and function tests (e.g. effective compliance of the respiratory system). The chest roentgenogram also apprises of the development, and consequently of the need for treatment, of such complications as interstital emphysema, pneumothorax, pneumomediastinum, pneumoperitoneum and subcutaneous emphysema.

Humans↗

Effect of chest strapping on regional lung function.

We studied lung mechanics and regional lung function in five young men during restrictive chest strapping. The effects on lung mechanics were similar to those noted by others in that lung elastic recoil increased as did maximum expiratory flow at low lung volumes. Chest strapping reduced the maximum expiratory flow observed at a given elastic recoil pressure. Breathing helium increased maximum expiratory flow less when subjects were strapped than when they were not. These findings indicated that strapping decreased the caliber of airways upstream from the equal pressure point. Regional lung volumes from apex to base were measured with xenon 133 while subjects were seated. The distribution of regional volumes was measured at RV, and at volumes equal to strapped FRC and strapped TLC; no change due to chest strapping was observed. Similarly, the regional distribution of 133Xe boluses inhaled at RV and strapped TLC was unaffected by chest strapping. Closing capacity decreased with chest strapping. We concluded that airway closure decreased during chest strapping and that airway closure was not the cause of the observed increase in elastic recoil of the lung. The combination of decreased slope of the static pressure-volume curve and unchanged regional volumes suggested that strapping increased the apex-to-base pleural pressure gradient.

Adult↗