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Biomedical subjects

S H Thomas

Publications and source records attributed to S H Thomas.

At least 91 records · Page 5Linked to original sources

Delivery of ultrasonic nebulized aerosols to a lung model during mechanical ventilation.

Ultrasonic nebulizers may be particularly suitable for the administration of therapeutic aerosols to patients undergoing mechanical ventilation, but the amount of aerosol that reaches the patients' respiratory tract during ultrasonic nebulization has not been adequately studied. The delivery through an endotracheal tube of nebulized aerosols labeled with 99mTechnetium human serum albumin was therefore measured for five commercially available ultrasonic nebulizers using an in vitro model representing mechanical ventilation of an adult patient. Delivery of aerosol through the endotracheal tube ranged from 3.1 +/- 0.3% for Samsonic to 10.1 +/- 2.0% for Portasonic using 3 ml nebulizer solution. Increasing the volume of nebulizer solution to 18 ml (not possible for the Portasonic) increased delivery to 11.5 +/- 2.0 for the DP 100, 8.7 +/- 3.1 for Ultraneb, and 15.9 +/- 1.8% for Samsonic. Addition of a 600 ml aerosol storage chamber to the ventilator circuit increased delivery for the Samsonic (18 ml solution) to 22.3 +/- 5.0%. Aerosol delivery was also increased by reducing the respiratory rate and minute volume and by increasing the inspiratory time settings on the ventilator. These results confirm the potential value of ultrasonic nebulizers during mechanical ventilation and indicate that clinical trials in ventilated patients are warranted.

Adult↗

Differential cardiovascular effects of propranolol, atenolol, and pindolol measured by impedance cardiography.

We have evaluated Sramek's method of impedance cardiography as a non-invasive way of detecting the cardiovascular effects of drugs. We made cardiovascular measurements using the method during passive tilting and exercise 2 h after the oral administration of atenolol (50 and 100 mg), propranolol (40 and 80 mg), pindolol (5 and 10 mg), and placebo in seven separate studies involving eight healthy male volunteers. Equivalent doses of the pure antagonists atenolol (beta 1) and propranolol (beta 1, beta 2) produced similar reductions in heart rate, systolic blood pressure, and cardiac index, and increases in stroke volume and total peripheral resistance, particularly during exercise. In contrast the partial agonist pindolol produced increases in heart rate and cardiac index, and reductions in peripheral resistance at rest. During passive tilting and exercise pindolol reduced heart rate, but cardiac output and total peripheral resistance were unchanged except at the highest levels of exercise. The similar cardiovascular effects of atenolol and propranolol, but differing effects of pindolol, are consistent with reports using other methods of measurement. This suggests that impedance cardiography may have a place in the non-invasive assessment of the cardiovascular effects of drugs.

Adult↗

The haemodynamic responses to venesection and the effects of cardiovascular disease.

The haemodynamic effects of the venesection of one unit (450 ml) of blood over 9 min were measured using non-invasive techniques, in 14 healthy controls and 18 patients with coronary heart disease or hypertension. Venesection was associated with significant reductions in supine and standing systolic and diastolic blood pressure, stroke volume index and cardiac index, and increases in standing heart rate, in both patient groups. No significant differences were observed between the responses of subjects with and without cardiovascular disease. The authors conclude that, in contrast to established teaching, blood loss can be detected in its early stages by careful haemodynamic monitoring and that venesection can be performed safely without volume replacement in patients with stable cardiovascular disease.

Adult↗

Delivery of a nebulized aerosol to a lung model during mechanical ventilation. Effect of ventilator settings and nebulizer type, position, and volume of fill.

Several factors may affect the delivery of a nebulized aerosol to the lung through an endotracheal tube during mechanical ventilation. To study these factors in vitro, a model representing ventilation of an adult patient was constructed by linking a Servo 900C ventilator to a standard humidified circuit and an endotracheal (ET) tube positioned within a pipe representing the trachea. This was connected via a filter to a lung simulator. Nebulizers filled with 99mTc human serum albumin were positioned in the circuit, and the delivery of nebulized aerosol through the ET tube into the filter was measured using a gamma camera. With the use of an inspiratory phase-activated System 22 Acorn jet nebulizer, typical adult ventilator settings, and a 3-ml nebulizer solution volume, 5.4% of the nebulizer dose reached beyond the end of the ET tube. This was increased by increasing the inspiratory time, reducing the respiratory rate or respiratory minute volume, and by repositioning the nebulizer on the inspiratory limb of the Y-piece and was reduced by slowing the driving gas flow to the nebulizer. Under the same conditions, delivery was 3.1 and 4.4% using the Samsonic and Fisoneb ultrasonic nebulizers, respectively. Increasing the fill volume and the addition of an aerosol storage chamber increased delivery with all three nebulizers. These experiments suggest some simple ways of improving aerosol delivery during mechanical ventilation, including increasing the volume of nebulizer fill, repositioning the nebulizer in the ventilator circuit, adding an aerosol storage chamber, and adjusting ventilator settings to maximize delivery.

Adult↗

Impedance cardiography using the Sramek-Bernstein method: accuracy and variability at rest and during exercise.

1. Sramek and Bernstein's method of impedance cardiography is a simple, non-invasive and inexpensive computerised way of measuring stroke volume and systolic time intervals. In this study measurements made using the method were compared with those found simultaneously using established reference techniques. 2. In healthy volunteers there was no significant bias (d) and narrow 95% limits of agreement (d +/- 2s) when impedance and mechanophonocardiographic measurements of pre-ejection period (PEP, d = 0.3, d + 2s = 7.3, d-2s = -6.6 ms), ventricular ejection time (VET, d = 1.5, d + 2s = 17.7, d-2s = 14.6 ms) and PEP/VET ratio were compared. 3. In critically ill patients there was moderate agreement between impedance and thermodilution measurements of stroke volume (d = 8.1 (P < 0.05), d + 2s = 35.5, d-2s = -19.4 ml) and drug-induced changes in stroke volume were accurately detected. 4. In healthy volunteers agreement between impedance and dye dilution measurements of stroke volume was moderate, and similar at rest and during exercise (d = 3.4, d-2s = -31.1, d + 2s = 37.9 ml), however impedance underestimated exercise-induced increases in stroke volume (P < 0.05). 5. In patients with coronary heart disease impedance measurements correlated with angiographic left ventricular ejection fraction included the PEP/VET ratio (r = -0.81), stroke volume index (r = 0.65) and Heather index (r = 0.58, all P < 0.001), however the PEP/VET ratio could not be used to estimate the left ventricular ejection fraction with sufficient accuracy. 6. This impedance method provides reproducible semi-quantitative measurements of cardiac performance and blood flow. Its use for making pharmacodynamic measurements can be justified when invasive methods are considered inappropriate.

Adult↗

Factors influencing the ocular pulse--the heart rate.

Using pneumotonometry combined with a Langham ocular blood-flow system, measurements of pulsatile ocular blood flow (POBF) were performed in eight ocular normotensive patients with implanted cardiac pacemakers, with the subjects assuming both the erect and the supine postures. Sequential measurements of POBF were made at pre-set values of heart rate over the physiological range between 60 and 120 beats/min at intervals of 10 beats/min. With patients in the supine position, measurements of cardiac output and stroke volume indices were also recorded by impedance cardiography. The mean pulse amplitude of the intraocular pressure (the ocular pulse) decreased as heart rate increased, and this change was statistically significant in both postures according to repeated-measures analysis of variance (erect: f = 18.7, P less than 0.0001; supine: f = 18.8, P less than 0.0001). As measured in supine patients following an increase in heart rate, the pulse amplitude decreased in parallel with a decline in stroke volume index (f = 18.8, P less than 0.0001). Up to a level of 90 beats/min, the mean POBF increased with heart rate, but it declined above this rate in both erect and supine postures. At all heart rates, intraocular pressure was higher when subjects were supine than when they stood erect (f = 4.3, P less than 0.001). At lower heart rates of 70 and 80 beats/min, ocular pulse volume and POBF were significantly lower in supine patients than in erect subjects (70 beats/min: t = 3.89, P less than 0.01 vs; t = 3.87, P less than 0.01; 80 beats/min: t = 2.85, P less than 0.05 vs; t = 2.87, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Comparison of the cardiovascular effects of nifedipine and nicardipine in the presence of atenolol.

A placebo controlled double blind crossover study was performed in 12 healthy volunteers to compare the cardiovascular effects of single oral doses of nifedipine (5, 10 and 15 mg) and nicardipine (20 and 30 mg) in the presence of atenolol 100 mg. Haemodynamic measurements were made by transthoracic electrical bioimpedance cardiography (TEBC) 2 h following drug administration during passive tilting, graded bicycle exercise (30-150 W) and recovery from exercise. In the absence of calcium channel blockade, atenolol reduced mean blood pressure, heart rate, and cardiac index, and increased stroke volume, peripheral resistance, pre-ejection period, and ventricular ejection time, particularly during and after exercise. In comparison with atenolol alone, addition of nifedipine or nicardipine reduced peripheral resistance but did not produce significant changes in stroke volume, cardiac output, dZ/dt [max], pre-ejection period (PEP). Ventricular ejection time (VET), PEP/VET, or Heather index at any point in the experiment. Similar reductions in peripheral resistance were produced by nifedipine 10 mg and nicardipine 20 and 30 mg. These apparently equivalent doses of nifedipine and nicardipine had similar effects on stroke volume, cardiac index, PEP/VET and Heather index. Thus the increases in ventricular performance previously demonstrated in association with nifedipine and nicardipine therapy were not observed in the presence of beta-adrenoceptor blockade. Under these conditions no important differences have been observed in the cardiovascular effects of these two calcium channel blockers.

Administration, Oral↗

Role of bile acids in splanchnic hemodynamic response to chronic portal hypertension.

Previous studies from our laboratory suggest that humoral factors, namely glucagon, can account for approximately 30% of the splanchnic vasodilation in rats with prehepatic portal hypertension. A reduced vascular sensitivity to norepinephrine, vasopressin, and angiotensin II may contribute to the splanchnic vasodilation. However, neither glucagon nor an altered vasoconstrictor sensitivity can fully account for the splanchnic vasodilation observed in portal hypertensive subjects. Therefore, the present study was designed to examine the role of bile acids in the splanchnic hyperemia of portal hypertension since (1) serum bile acids are elevated in portal hypertensive subjects and (2) bile acids are potent intestinal vasodilators. Prehepatic portal hypertension was induced in Sprague-Dawley rats by surgical constriction of the portal vein. Ten to 14 days after the induction of portal hypertension, the enterohepatic circulation of control and portal hypertensive rats was surgically interrupted. The animals were placed in Bollman restraint cages and allowed to recover. Eighteen to 24 hr later, the rats were anesthetized with sodium pentobarbital and regional blood flow measured with radiolabeled microspheres. Normal and portal hypertensive animals without bile fistula served as controls. Plasma bile acid levels measured by radioimmunoassay were approximately 3.8 times higher in portal hypertensive animals than in control. Bile duct cannulation effectively depleted both normal and portal hypertensive animals of their circulating bile acid pool and significantly reduced portal venous inflow in portal hypertensive but not in control rats. A role for bile acids as partial mediators of the splanchnic hyperemia of portal hypertension is suggested since bile acid depletion did not completely abolish the gastrointestinal hyperemia.

Animals↗

Variability in the measurement of nebulized aerosol deposition in man.

1. This study was performed to determine the variability of two different scintigraphic methods of measuring pulmonary aerosol deposition, and to examine nebulizer particle size and drug output as potential sources of this variability. 2. A radioaerosol was produced from a 3 ml solution of 99mTc-labelled colloidal human serum albumin (0.05 mg, 37 MBq) using a standard jet nebulizer and air compressor. This was inhaled on three separate occasions by nine healthy male subjects. One one of these occasions, a further inhalation was performed to assess immediate repeatability using increased 99mTc activity (92 MBq). 3. Intrapulmonary aerosol deposition was measured with a gamma-camera and was corrected for tissue attenuation and geometric distribution by using two different methods. 4. Estimated mean pulmonary deposition was 4.3% of the nebulizer dose using a lung phantom correction method, and 6.1% using a tissue attenuation method. For these two methods respectively variability between subjects (coefficient of variation) was 54 and 47%. For both methods, within-subject variability (coefficient of variation) was 37% between occasions and 23% within occasions. 5. The particle-size output of several nebulizers was highly reproducible (coefficient of variation less than 4%), but the nebulizer mass and radionuclide output of two nebulizers was more variable (coefficient of variation 5-19%), and appeared to be an important contributor to the variability in pulmonary aerosol deposition. 6. The data presented here for pulmonary deposition, used with appropriate power statistics formulae, can be used to estimate the sample sizes required for comparative studies of lung aerosol deposition.

Aerosols↗

Pulmonary deposition of nebulised amiloride in cystic fibrosis: comparison of two nebulisers.

BACKGROUND Preliminary evidence suggests that regular inhalation of nebulised amiloride reduces sputum viscoelasticity, increases the clearance of sputum by mucociliary mechanisms and by coughing and reduces the rate of deterioration in lung function in patients with cystic fibrosis. These effects depend on adequate delivery of amiloride to the airways. This study was performed to quantify and compare pulmonary deposition of amiloride produced by two different nebuliser systems. METHODS The pulmonary deposition of nebulised amiloride (1 mg in 3 ml saline) was measured in eight patients with cystic fibrosis when given via a jet (System 22 with CR 60 compressor) and an ultrasonic (Fisoneb) nebuliser. Human serum albumin labelled with technectium-99m was used as an indirect marker for amiloride and its deposition in the lung was detected with a gamma camera. RESULTS Amiloride inhalation caused no side effects or changes in spirometric indices. The mean (SD) total pulmonary amiloride deposition was 57 (24) micrograms with the System 22 and 103 (53) micrograms with the Fisoneb nebuliser. Pulmonary deposition was completed more rapidly with the Fisoneb (4-5 minutes) than with the System 22 nebuliser (7-8 minutes) and the Fisoneb was preferred by the patients. CONCLUSIONS Both nebulisers appeared to deliver adequate amounts of amiloride to the lungs, but treatment with the Fisoneb nebuliser was quicker, more efficient, and more acceptable to the patients. Of the two nebulisers assessed, the Fisoneb would be preferred for clinical trials.

Administration, Inhalation↗

A comparison of the cardiovascular effects of phenylpropanolamine and phenylephrine containing proprietary cold remedies.

1. The cardiovascular effects of the proprietary cold remedies, Mu-cron and Boots Cold Relief tablets were compared with 'placebo' Boots Pain Relief tablets in a double-blind study involving 16 healthy volunteers. Measurements (impedance cardiography, forearm plethysmography) were made over 4 h after oral drug administration. 2. Two Mu-cron tablets (containing phenylpropanolamine [(1R,2S)- plus (1S,2R)-norephedrine] 50 mg) increased blood pressure (maximal effect 18 +/- 1/8 +/- 1 mm Hg (mean +/- s.e. mean), P less than 0.001), stroke volume (4.9 +/- 0.8 ml m-2, P less than 0.05), total peripheral resistance (243 +/- 27 dyn s cm-5 m2, P less than 0.001) and forearm vascular resistance (1.3 +/- 0.3 mm Hg ml-1 min, P less than 0.01) and reduced the ratio of pre-ejection period to ventricular ejection time (-0.031 +/- 0.003, P less than 0.05) and forearm blood flow (-2.6 +/- 0.5 ml min-1, P less than 0.05) but did not affect heart rate or cardiac index. 3. Two Boots Cold Relief tablets (containing phenylephrine 10 mg and caffeine 60 mg) caused a small and short-lived increase in total peripheral resistance but did not have consistent effects on other measurements. Two Boots Pain Relief tablets (containing caffeine 60 mg) did not have important cardiovascular effects. 4. The cardiovascular effects of phenylpropanolamine, including vasoconstriction and an increase in cardiac performance, are consistent with its alpha- and beta 1-adrenoceptor agonist action. While it may help the symptoms of rhinitis, its use in patients with heart disease or hypertension is hazardous.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Which apparatus for inhaled pentamidine? A comparison of pulmonary deposition via eight nebulisers.

Aerosolised pentamidine 300 mg in 5 or 6 ml solution was administered via 8 different nebuliser systems to 12 patients with acquired immunodeficiency syndrome. Using 99mTc human serum albumin as an indirect marker for pentamidine, pulmonary, extrapulmonary (gastric and oropharyngeal) and alveolar deposition of pentamidine were measured using a gamma camera. Side effects (visual analogue scales) and changes in lung function associated with each treatment were also quantified. Deposition was completed more rapidly with the ultrasonic than the jet nebulisers. Mean total pulmonary depositions (mg +/- SEM) were Respirgard II, 6.1 +/- 0.5; Centimist, 7.3 +/- 1.0, System 22 Mizer, 14.3 +/- 2.1; System 22 Mizer with particle separator; 4.5 +/- 0.4; System 22 Mizer with Optimist 2, 6.3 +/- 0.9; Fisoneb, 6.0 +/- 1.2; Pentasonic (Portasonic); 4.6 +/- 0.9; Samsonic, 2.9 +/- 0.4. Differences between the nebulisers for peripheral lung and alveolar deposition reflected this pattern. Side effects scores were largest with System 22 Mizer, Pentasonic (Portasonic), and Fisoneb, and these produced the greatest oropharyngeal and gastric deposition. The largest reductions in lung function were associated with System 22 Mizer. A 300 mg dose of pentamidine nebulised via Respirgard II is known to be effective prophylaxis for Pneumocystis carinii pneumonia when given once monthly. Our results show that equivalent pulmonary deposition can be produced by other nebulisers. System 22 Mizer gives over twice the deposition associated with Respirgard II, and used with a pentamidine dose of 150 mg is likely to produce an adequate lung dose for prophylaxis. This nebuliser, however, is associated with more marked side effects.

Acquired Immunodeficiency Syndrome↗

The cardiovascular effects of oral nifedipine and nicardipine: a double-blind comparison in healthy volunteers using transthoracic bioimpedance cardiography.

The cardiovascular effects of single oral doses of nifedipine (5 and 10 mg) and nicardipine (20 and 30 mg) were compared in a placebo controlled double-blind crossover study involving 8 healthy male volunteers. Two hours following drug administration stroke volume and cardiac index were measured non-invasively using transthoracic electrical bioimpedance cardiography during passive tilting, graded bicycle exercise, and recovery from exercise. Two separate experiments were performed in the absence of active drug to allow the reproducibility of the measurements to be assessed. Coefficients of variation (within experiment/between experiments) for cardiac index were 7.0%/19.9% at rest and 11.5%/9.3% at 180 W exercise. Both nifedipine and nicardipine increased stroke volume and cardiac index and reduced total peripheral resistance (mean blood pressure/cardiac index) at all times in the experiment. Reductions in peripheral resistance were similar for nifedipine 10 mg and nicardipine 20 mg but in these doses slightly larger increases in heart rate were produced by nifedipine, and in stroke volume and cardiac index with nicardipine. The study shows that the cardiovascular effects of nifedipine and nicardipine can be detected using impedance cardiography which is a simple, safe, and inexpensive technique. The differences between the effects of the two drugs were small. Although some were of statistical significance and are consistent with a less marked cardiodepressant effect for nicardipine, the clinical importance of these observations is uncertain. Further studies to examine the effect of oral nifedipine and nicardipine in patients with impaired ventricular function may be helpful in clarifying this tissue.

Administration, Oral↗

Does inhalation of pentamidine in the supine position increase deposition in the upper part of the lung?

To assess the effect of posture on the distribution of nebulized pentamidine isethionate deposition in the lung, ten patients with AIDS were studied. Two nebulizer systems, System 22 Mizer (MedicAid) and Respirgard II (Marquest) were modified by adding 40 cm of corrugated tubing (volume 150 ml) to allow the patients to be studied in both the sitting and supine posture. Modification of the nebulizers caused a reduction in lung deposition in the sitting position for the System 22 Mizer but increased deposition in the Respirgard II compared with the unmodified apparatus. The ratio of upper to lower zone deposition (corrected for 133Xe distribution) was increased in the supine position for both devices (p less than 0.01). The best upper zone deposition was achieved with the unmodified System 22 Mizer in the sitting position. Respirgard II had the lowest nonpulmonary deposition and the lowest incidence of adverse effects. The supine position was associated with a redistribution of deposition to the upper zones. To attempt to reduce upper zone recurrence of Pneumocystis carinii pneumonia, the supine posture is suggested for less efficient nebulizer devices, ie, the Respirgard II, but for more efficient systems, ie, System 22 Mizer, the sitting position is probably suitable. This postulate needs to be confirmed by a clinical trial.

Acquired Immunodeficiency Syndrome↗

Clinical versus biochemical assessment in thyroxine replacement therapy: a retrospective study.

A retrospective audit of a thyroid clinic revealed that only 67% of clinical assessments of thyroid status in patients receiving thyroxine replacement therapy were correct. The identification of patients on excessive doses of thyroxine appears to be the most difficult by clinical assessment alone, only 10% of those patients with a suppressed TSH level being identified. This study emphasises the importance of thyroid function tests in the assessment of patients on thyroxine replacement.

Adult↗