Evolución clínica de la uveítis intermedia asociada a infección por el virus linfotrópico de células T humano tipo 1 (HTLV-1) / Clinical course of HTLV-1 infection associated intermediate uveitis

Objetivo: Describir las características asociadas a la presentación, tratamiento y seguimiento de una serie de casos de uveítis intermedia asociada al virus linfotrópico de células T humano de tipo 1 (HTLV-1).Pacientes y métodosEstudio retrospectivo, descriptivo y longitudinal. Se incluyó a pacientes con uveítis intermedia asociada a infección por HTLV-1 atendidos en una clínica oftalmológica de referencia de Lima (Perú), durante 2012-2018.ResultadosSe incluyó a 18 pacientes (28 ojos). La edad promedio a la presentación fue de 57,3 años; el 66,6% fueron mujeres. El tiempo de seguimiento promedio fue de 1.280 días. Los síntomas más frecuentes fueron visión borrosa o disminuida (78,6%) y visión de cuerpos flotantes (57,1%). La agudeza visual mejor corregida fue de 20/40 o mejor en el 53,6%. La presión intraocular inicial promedio fue de 14,95mmHg. Se observaron precipitados retroqueráticos en el 50% de ojos, siendo el tipo más frecuente el espiculado (17,9% de los ojos). El tratamiento más frecuente fue la inyección periocular de corticoides (en el 53,6% de los ojos). Se presentaron complicaciones como membrana epimacular (50%), catarata (21,4%) y glaucoma (7,1%). Al final del seguimiento, solo 2 ojos perdieron una línea de visión; la agudeza visual mejor corregida final fue de 20/40 o mejor en el 85,7%, y de 20/70 o mejor en el 96,4%. Los pacientes afectados en ambos ojos aumentaron de 33% a la presentación a 55,5%. El curso de la enfermedad fue crónico en el 60,7%.ConclusiónLa uveítis intermedia asociada a infección por HTLV-1 se presentó principalmente en la segunda mitad de la vida, con curso crónico y buen pronóstico visual. (AU)

Objective: To describe the clinical features at presentation, delivered treatment and follow-up of a case series of human T-cell lymphotropic virus type 1 (HTLV-1) associated intermediate uveitis.Patients and methodsRetrospective, descriptive and longitudinal study of patients with HTLV-1 associated intermediate uveitis treated at a reference ophthalmology facility in Lima, Peru, during the years 2012 to 2018.ResultsA total of 18 patients (28 eyes) were included, the average age at presentation was 57.3 years, 66.6% were women, and the average follow-up time was 1,280 days. The most frequent symptoms were blurred or diminished vision (78.6%) and floaters (57.1%). Best corrected visual acuity was 20/40 or better in 53.6%. The mean initial intraocular pressure was 14.95mmHg. Keratic precipitates were observed in 50% of eyes, 17.9% were of the stellate type. The most frequent treatment was periocular corticosteroid injections (53.6%). Complications such as epimacular membrane (50%), cataract (21.4%) and glaucoma (7.1%) occurred. At the end of follow-up, only 2 eyes lost one line of vision; the final best corrected visual acuity was 20/40 or better in 85.7%, and 20/70 or better in 96.4%. Patients with both eyes affected increased from 33% at presentation to 55.5%. The course of the disease was chronic in 60.7%.ConclusionHTLV-1 associated intermediate uveitis mainly occurred in patients in the second half of life, developing a chronic course and with good visual prognosis. (AU)

Clinical course of HTLV-1 infection associated intermediate uveitis.

OBJECTIVE: To describe the clinical features at presentation, delivered treatment and follow-up of a case series of human T-cell lymphotropic virus type 1 (HTLV-1) associated intermediate uveitis. PATIENTS AND METHODS: Retrospective, descriptive and longitudinal study of patients with HTLV-1 associated intermediate uveitis treated at a reference ophthalmology facility in Lima, Peru, during the years 2012 to 2018. RESULTS: A total of 18 patients (28 eyes) were included, the average age at presentation was 57.3 years, 66.6% were women, and the average follow-up time was 1,280 days. The most frequent symptoms were blurred or diminished vision (78.6%) and floaters (57.1%). Best corrected visual acuity was 20/40 or better in 53.6%. The mean initial intraocular pressure was 14.95 mmHg. Keratic precipitates were observed in 50% of eyes, 17.9% were of the stellate type. The most frequent treatment was periocular corticosteroid injections (53.6%). Complications such as epimacular membrane (50%), cataract (21.4%) and glaucoma (7.1%) occurred. At the end of follow-up, only 2 eyes lost one line of vision; the final best corrected visual acuity was 20/40 or better in 85.7%, and 20/70 or better in 96.4%. Patients with both eyes affected increased from 33% at presentation to 55.5%. The course of the disease was chronic in 60.7%. CONCLUSION: HTLV-1 associated intermediate uveitis mainly occurred in patients in the second half of life, developing a chronic course and with good visual prognosis.

Benazepril, an angiotensin converting enzyme inhibitor: drug interaction with salbutamol and bronchial response to histamine in normal subjects.

AIMS: To investigate the effect of the angiotensin converting enzyme inhibitor, benazepril, on pulmonary function. METHODS: We investigated the influence of benazepril, on lung function and the interaction with inhaled salbutamol (0.1 to 6.6 mg) and histamine (0.03 to 30.69 g l-1) in normal subjects. Benazepril 20 mg, salbutamol 8 mg, propranolol 160 mg, and placebo were given orally once daily over 10 days. RESULTS: On day 8, there was no difference in the area under the salbutamol dose-response curves between benazepril, placebo and oral salbutamol (P > 0.05), propranolol shifted the curves to the right (P < 0.05). On day 10, histamine challenge resulted in following PD35sGaw values (geometric mean and 95% CI): with placebo 1.02 (0.95-1.09) g l-1, benazepril 1.04 (0.99-1.08), salbutamol 1.19 (1.13-1.25), propranolol 0.57 (0.50-0.65). CONCLUSIONS: Benazepril had no influence on baseline lung function, caused no interaction with inhaled salbutamol and the bronchial response to histamine was similar to placebo. However, our findings in normal subjects cannot be extrapolated automatically to asthmatics.

Effect of solution and suspension type aerosol of formoterol on tremor response and airways in patients with asthma.

BACKGROUND: Aerosol delivery and deposition to the oropharynx and the lungs have been found to be different for solution-type and suspension-type metered-dose aerosols used for treatment of asthma. We investigated possible differences in clinical effects between solution and suspension metered-dose formoterol aerosols. METHODS: A total of 24 patients with asthma (forced expiratory volume in 1 second, < or = 70% predicted) inhaled single doses (12 micrograms or 24 micrograms) of formoterol solution and suspension so that we could investigate the immediate tremor, airway, and cardiovascular responses in a randomized, double-blind, crossover trial. Fenoterol suspension aerosol (400 micrograms) was used for comparison (single-blind, poststudy, nonrandomized administration). Fenoterol (400 micrograms) as a rescue medication was inhaled after 120 minutes on each of the 5 study days. RESULTS: The order of mean (+/- SEM) maximum tremor acceleration was as follows: 12 micrograms formoterol solution (67.92 +/- 4.54 cm x sec-2) < 24 micrograms solution (73.46 +/- 4.51 cm x sec-2) < 12 micrograms suspension (80.87 +/- 5.08 cm x sec-2) < fenoterol (84.13 +/- 4.21 cm x sec-2) < 24 micrograms formoterol suspension 88.54 +/- 6.26 cm x sec-2). Maximum increase in specific airway conductance ranged from 0.48 +/ 0.03 to 0.55 +/- 0.04 sec-1 x kPa-1 for all drugs (p > 0.05). No change in cardiovascular parameters occurred (p > 0.05). CONCLUSION: No difference in the bronchial response to either formulation of formoterol was found. Tremor response to suspension aerosol (24 micrograms > 12 micrograms) was higher than that to solution aerosol (24 micrograms > 12 micrograms), indicating possible differences in systemic absorption because of a different deposition pattern. Rescue medication demonstrated systemic effects on tremor that were additive to those of formoterol.

Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2-adrenergic receptors.

This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 micrograms) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P > .05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P < .05), whereas metoprolol was indistinguishable from placebo (P > .05). The median cumulative salbutamol concentrations causing a 50% increase in specific airway conductance were 416 and 384 micrograms (days 1 and 7, respectively) for placebo, 594 and 444 micrograms for metoprolol, and 562 and 1419 micrograms for atenolol. The median cumulative salbutamol concentrations causing a 35% increase in tremor were 732 and 706 micrograms for placebo, 812 and 1213 micrograms for metoprolol, and 797 and 1323 micrograms for atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on the bronchodilator, tremorogenic, cardiovascular and hypokalaemic effects of fenoterol dry powder in asthma.

1. The airway and tremor response and cardiovascular and hypokalaemic effects of single and cumulative doses of fenoterol given by dry powder capsules (DPC) and by metered dose inhaler (MDI) were studied in asthmatics in two randomized, crossover trials. 2. Single doses of fenoterol DPC and MDI (0.2 mg, 0.4 mg), investigated in 24 subjects, produced similar, dose-dependent increases in FEV1. Fenoterol DPC caused less tremor response and less hypokalaemic effects than fenoterol MDI. 3. Cumulative doses of fenoterol DPC and MDI (0.2, 0.6, 1.4, 3.0, 6.2 mg), investigated in 12 subjects, produced a comparable bronchodilatation (mean maximum increase in FEV1 was 0.53 +/- 0.06/0.52 +/- 0.081 for DPC/MDI) and a similar, dose-dependent rise in heart rate (35 +/- 3.81/41 +/- 2.25 beats min(-1)). The rise in tremor and the fall in plasma potassium were smaller after DPC than after MDI. The mean maximum changes were 51.58 +/- 6.41/95.83 +/- 6.75 cm s(-2) for tremor and -0.68 +/- 0.09/-0.96 +/- 0.10 mmol l(-1) for potassium. 4. Our findings may result from a difference in the pharmacokinetics of the dry powder and the aerosol formulation, particularly differences in distribution and absorption. 5. In conclusion, fenoterol DPC used in low therapeutic doses (0.2,0.4 mg), is preferable to the MDI. Fenoterol DPC used as rescue medication in high cumulative doses, do not suggest a greater safety margin than the MDI and the same restrictions should be considered for the fenoterol dry powder formulation as suggested for the MDI.

Assessment of beta-adrenergic receptor blockade after isamoltane, a 5-HT1-receptor active compound, in healthy volunteers.

This study investigated the effects of isamoltane on the changes induced by cumulative doses of inhaled albuterol (salbutamol) on bronchomotor tone, skeletal muscle, circulatory system, and metabolism after single (day 1) and multiple dosing (day 7) in 15 healthy subjects. The volunteers were given placebo, 4 mg isamoltane, 10 mg isamoltane, or 20 mg propranolol over a 7-day period in a randomized, double-blind, crossover design. The greatest attenuation in albuterol-induced beta-adrenergic receptor responses occurred with propranolol. The median provocative dose of albuterol causing a 50% increase in specific airway conductance was 337 and 315 micrograms (day 1 and day 7, respectively) for placebo, 336 and 322 micrograms for 4 mg isamoltane, 344 and 389 micrograms for 10 mg isamoltane, and 667 and 652 micrograms for propranolol. The provocative dose of albuterol producing a 35% increase in tremor was 464 and 539 micrograms (day 1 and day 7, respectively) for placebo, 1122 and 1270 micrograms for 4 mg isamoltane, 1612 and > 1612 micrograms for 10 mg isamoltane, and > 1612 and > 1612 micrograms for propranolol. On day 5 of each period an exercise test was performed. Propranolol reduced exercise heart rate by 11% (compared with placebo), 10 mg isamoltane reduced heart rate by 5%, and 4 mg isamoltane reduced heart rate by 1%. In conclusion, low-dose isamoltane caused measurable systemic effects on both beta 2- and beta 1-adrenergic receptors, and the dose-dependent blockade on beta 2-receptors of skeletal muscle was more clear than the attenuation of exercise heart rate.

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Assessment of bronchial effects following topical administration of butylamino-phenoxy-propanol-acetate, an oculoselective beta-adrenoceptor blocker in asthmatic subjects.

1. Butylamino-phenoxy-propanol-acetate (BPPA) is a new topical oculoselective beta-adrenoceptor blocker for the reduction of intraocular pressure (IOP) in man. Its potency on the airways of normal subjects was identical with that of placebo. A study was carried out to determine the potential of BPPA to cause bronchoconstriction in mild asthmatics (FEV1 greater than or equal to 60% predicted) with normal IOP. 2. Twelve nonsmoking outpatients who bronchoconstricted to 0.25 or 0.50% of timolol eye drops (fall in FEV1 23.33 +/- 1.20% (mean +/- s.e. mean), range 16-30) were investigated in this double-masked, randomized, 3-period, crossover study. On three different occasions six incremental concentrations of BPPA (range: 0.1-2%; maximum cumulative concentration 4%), timolol (0.1-1%; 2%), and placebo were administered bilaterally until bronchoconstriction (decrease in FEV1 greater than or equal to 20% and in specific airway conductance (sGaw) greater than or equal to 35% simultaneously) or the maximum cumulative concentration was reached. 3. Airway response was measured as change in FEV1 and sGaw and dose-response curves to timolol, BPPA and placebo were performed. IOP was measured 3 h after the highest concentration of each study day. 4. Timolol caused dose-dependent falls in FEV1 and sGaw as well as clinical symptoms of respiratory distress in all subjects. The median cumulative concentrations of timolol required to decrease FEV1 by 20% and sGaw by 35% were 0.98% and 1.53%. Neither placebo (P greater than 0.05) nor BPPA (P greater than 0.05) caused a significant change in sGaw. A fall in FEV1 by 20% not accompanied by a simultaneous fall in sGaw by 35% was found in four subjects following BPPA and in five subjects following placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of systemic effects of different ophthalmic beta-blockers in healthy volunteers.

Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.

Dose related protective effect of azelastine on histamine induced bronchoconstriction in extrinsic asthma.

The effect of single oral doses of the antiallergic agent azelastine hydrochloride (1.1, 2.2 and 4.4 mg) was compared to placebo on airway response to histamine challenge in 12 asymptomatic extrinsic asthmatics with proven bronchial hyperresponsiveness to inhaled histamine in a randomized double-blind crossover trial. All doses of azelastine resulted in a significant protection compared to placebo. The effects of 2.2 and 4.4 mg were equivalent and superior compared to 1.1 mg. A naturally small but statistically significant bronchodilator effect was observed 4 h after the two higher doses of azelastine. Tiredness was reported by two patients, the symptom occurred following each placebo and the active drug.

Pulmonary effects of long-term beta 2-blockade in healthy subjects: comparative study of metoprolol OROS.

The effects on airway response of metoprolol OROS (oral osmotic) and three other long-acting beta-adrenoceptor blockers were studied. This was a placebo-controlled, randomized, five-period, single-blind, crossover trial in 15 healthy volunteers. Bronchial beta-blockade was estimated as the displacement of the salbutamol bronchodilator response of specific airway conductance (SGAW) measured by whole-body plethysmography. Metoprolol OROS (14/190 mg), slow-release (SR) metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg), and placebo were given once daily for 7 days. Inhaled salbutamol was administered at peak drug levels in cumulative doses of 12.5 to 800 micrograms on day 5 and in a single dose of 400 micrograms on day 7. On day 5, salbutamol induced significant increases in SGAW in each treatment group. SGAW increased after the single dose of salbutamol on day 7 in all groups and then declined steadily. The highest values were found after placebo and metoprolol OROS, with smaller increases after SR metoprolol, atenolol, and LA propranolol, the latter showing the smallest increase. Therefore, it would appear that under steady-state conditions, beta 2-bronchial receptors are least blocked by metoprolol OROS, followed by SR metoprolol, atenolol, and LA propranolol.

[Clinico-pharmacologic study of a new sustained-release oral salbutamol preparation in patients with obstructive airway disease]. / Klinisch-pharmakologische Untersuchungen mit einem neuen retardierten oralen Salbutamol bei Patienten mit obstruktiver Atemwegserkrankung.

A new sustained release preparation of oral salbutamol (8 mg) was compared to salbutamol (8 mg) and placebo in 15 patients suffering from chronic obstructive airways disease in a randomized double-blind cross-over trial. Changes in airways resistance and amplitude of finger tremor as well as subjective assessment of side effects (tremors, unrest, palpitations) revealed a longer lasting effect following the sustained release preparation of salbutamol.

Cardioselectivity of cetamolol compared with atenolol and nadolol.

The selectivity of the beta-adrenoceptor blockade produced by single oral doses of cetamolol, atenolol, and nadolol was compared in normal male subjects. Study 1 established the dose at which each drug provides equivalent beta-1 blockade. Beta-1 blockade was estimated using the degree of inhibition of the increased heart rate (HR) response to graded exercise. Cetamolol (30 mg), atenolol (100 mg), and nadolol (80 mg) all attenuated the HR response to a comparable extent. This result established that the dose ratio of cetamolol:atenolol:nadolol of 1.00:3.33:2.67 provides equipotent beta-1 blockade. This ratio of doses was used in Studies 2 and 3 to evaluate the antagonism of beta-2-mediated responses to titrated doses of intravenous isoproterenol (ISO) by low and high doses of each drug. Beta-2 blockade was assessed using the attenuation of ISO-induced reductions in diastolic blood pressure (DBP) in Study 2 and ISO-induced increases in specific airway conductance (sGAW) in Study 3. For within drug comparisons, antagonism of the HR increase induced by ISO (a response mediated by both beta-1 and beta-2 receptors) was also examined. Treatments included cetamolol (15 and 60 mg), atenolol (50 and 200 mg), and nadolol (40 and 160 mg in Study 2; 40 mg only in Study 3). All drugs tested suppressed the HR, DBP, and sGAW responses to ISO, and this blockade was dose dependent. Cetamolol and nadolol produced approximately equipotent beta-1 blockade, whereas cetamolol at both doses produced a less potent beta-2 blockade. Atenolol antagonized ISO effects on all parameters less than either cetamolol or nadolol. Quantitative cardioselectivity indices revealed that cetamolol 60 mg was the most cardioselective and nadolol 40 mg the least. Data from the three studies demonstrate that cetamolol is cardioselective relative to nadolol and that, in contrast to atenolol, cardioselectivity appears to increase at the higher dose.

[Protective effect of forskolin in acetylcholine provocation in healthy probands. Comparison of 2 doses with fenoterol and placebo]. / Protektiver Effekt von Forskolin gegenüber Acetylcholinprovokation bei gesunden Probanden. Vergleich von 2 Dosen mit Fenoterol und Placebo.

Forskolin, a potent adenylate cyclase activating diterpene-derivative, isolated from the Indian plant Coleus forskohlii, was tested double-blind and cross-over in 12 healthy volunteers (nonsmokers) by whole body plethysmography. All drugs were administered by metered dose inhalers. The bronchodilating effect (after 5 minutes) was as good as following fenoterol. At the beginning (after 3 and 5 minutes) the protective effect against inhaled acetylcholine was as good as following fenoterol while later on (after 15 and 30 minutes) fenoterol resulted in a stronger action.

[A single dose of theophylline in the evening in chronic obstructive airway disease. Serum concentration and lung function parameter]. / Abendliche Theophyllin-Einmaldosis bei chronisch obstruktiver Atemwegserkrankung. Serumkonzentrationen und Lungenfunktionsparameter.

In 12 patients with long-standing obstructive respiratory disease, the nocturnal Theophylline plasma levels were investigated after the administration in the evening, of 600 or 800 mg respectively Theophylline given in the form of sustained-release tablets (Uniphyllin), measurements being made on the first, 4th and 5th day of the study. Hourly plasma level measurements were made in the critical period between 4.00 and 8.00 hours. Already on the first study day, Theophylline plasma concentrations were higher than 10 micrograms/ml 5 to 11 hours after medication; on days 4 and 5, corresponding values were achieved after 3 hours. On these days, the course of the curve was virtually identical. Only very small standard deviations were found. Seven hours after medication, the plasma levels of Theophylline were at a peak. On average, this was 14.4 micrograms/ml on day 1, 18.1 micrograms/ml on day 4, and 17.7 micrograms/ml on day 5. Prior to the next dose of Theophylline at 21.00 hours, Theophylline plasma levels of 6.6 and 6.4 micrograms/ml were measured on days 4 and 5, respectively. These figures were thus appreciably above 5 micrograms/ml even after 24 hours. Between 4.00 and 8.00 hours, the Theophylline plasma levels were particularly high, so that in this biorhythmically critical period, the therapeutic effect of Theophylline following an evening single dose of Uniphyllin, is optimally developed.

[Treatment of chronic obstructive respiratory disease with a new purified theophylline preparation in delayed-action form]. / Behandlung der chronisch obstruktiven Atemwegserkrankung mit einem neuen reinen Theophyllin-Präparat in retardierter Form.

The treatment of chronic obstructive respiratory diseases with sustained release theophylline is steadily gaining in importance. Body plethysmography is applied for evaluating the extent of bronchospasmolysis during therapy of a new sustained release formula. A traditional prolonged-action theophylline-ethylenediamine preparation was administered to obtain comparative data. The sustained release formula containing pure theophylline meets the standards of a modern theophylline therapy. The graduation of the film tablet allows individualized dosage without losing the sustained release action by slowly increasing the theophylline-serum-level during a dosage interval of 12 hours.

Time course of the bronchial response to salbutamol after placebo, betaxolol and propranolol.

The effects on specific airway conductance (sGaw) of placebo, betaxolol and propranolol following the inhalation of salbutamol were studied in 8 healthy volunteers by whole body plethysmography. Each subject received placebo and single oral doses of betaxolol 40 mg and 80 mg, and propranolol 160 mg, and 320 mg. sGaw was measured before dosing and after 2 h, just before salbutamol was inhaled. It was then measured again after 15 min and 0.5, 1, 2, 3, 4 and 6 h. sGaw 2 h after the beta-blockers did not differ from the value whilst on placebo. The peak response to salbutamol after placebo and both doses of betaxolol was almost identical, whereas it was significantly reduced after propranolol. The AUC of the response to salbutamol over 6 h showed a reduction of 11% after betaxolol and of 19% after propranolol (p less than 0.01 between beta-blockers). The results indicate that, after betaxolol and in contrast to propranolol, a proportion of the bronchial beta 2-receptor population remains available to a beta 2-agonist.