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Biomedical subjects

D Beaumont

Publications and source records attributed to D Beaumont.

At least 37 records · Page 2Linked to original sources

Treatment of bronchial asthma with terfenadine; a randomized controlled trial.

1. Terfenadine, a histamine H1-receptor antagonist, was studied in 52 patients with stable mild perennial asthma with an allergic basis. 2. After a placebo run-in period, patients were randomly allocated to either terfenadine 120 mg twice daily or placebo. After 2 weeks they were crossed over to the other treatment. Forty-six patients completed the study. 3. Terfenadine was significantly more effective than placebo as measured by peak expiratory flows and by symptom scores. 4. These results suggest that histamine may play a more significant role in asthmatic bronchoconstriction than is currently recognised.

Adolescent↗

[Asthma and synthetic antihistaminics].

Anti-histamines are considered weakly effective in the treatment of asthma whether in acute exacerbations or as basic therapy. However, there are numerous arguments which plead in their favour, and not only the recognised role of histamines as an important mediator of the immediate response. Besides, since 1948 when it was shown that the first anti-histamines (classical anti-histamines) possessed undeniable anti-histamine like actions, which showed them to have both broncho-dilator activity and a protective effect on bronchospasm induced by inhalation of histamine or allergens. Unfortunately, this efficacy in asthma is only achieved with high doses which are responsible for troublesome side-effects. This is why with the arrival of new anti-histamines specific for H1 receptors, without anti-cholinergic or sedative effects, one can envisage the day when high dose anti-histamines are evaluated in the treatment of asthma. Pharmacological studies in animals have clearly shown their bronchomotor action. Similarly, the first work carried out in men, confirms the anti-asthmatic potential by showing a protective action in the bronchial response, to isocapnic hyperventilation, to exercise and to allergens. As for anti-H2, their impact on asthmatic broncho-constriction is poorly defined: for some they potentiate, for others they inhibit.

Animals↗

A double-blind comparison of terfenadine and mequitazine in the symptomatic treatment of acute pollinosis.

This study was a double-blind, parallel group comparison of terfenadine (TRF) 60 mg b.i.d. and mequitazine (MQZ) 5 mg b.i.d. for 7 days in the symptomatic treatment of acute pollinosis. The trial took place in the same geographic area and during the same pollen season (May-July 85), to ensure homogeneity of the study population. The fourteen investigators participating in this multicentre trial recruited 141 patients (69 TRF; 72 MQZ) suffering from well-documented pollinosis, mainly hay fever and sometimes allergy to tree pollens. Symptoms (nasal itching, sneezing, rhinorrhoea, obstruction, conjunctivitis) and possible somnolence were rated daily using a 4-point rating-scale of 0 to 3 by the patient on a diary card. Assessment of over-all efficacy and tolerability - focusing on atropinic side-effects - was made at the end of the seven-days treatment period by the physician, after reviewing the diary card and questioning the patient. The means score profile of each symptom for the study period was similar with the two treatments. Both had a fast onset of action with the regression of the total symptoms' score being already significant at day 1. Over-all assessment of efficacy at day 7 showed no significant difference between the two treatments. The daily somnolence scores however showed a clear and significant difference between the two drugs: the frequency of moderate to marked somnolence from day 2 to 7 was around 15% with MQZ and around 5% on days 2 to 5 and 0% on days 6 and 7 with TRF, the difference being significant on days 2, 5, 6 and 7.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Controlled, eight-hour haemodynamic study of a sustained-release formulation of isosorbide dinitrate in moderate left ventricular failure.

The aim of the study was to assess the duration of the haemodynamic effects of a new sustained-release oral formulation of isosorbide dinitrate (ISDN). Twenty patients (17 men and 3 women; mean age 60 years) with acute myocardial infarction (10 anterior, 10 inferior) complicated by moderate left ventricular failure took part in a randomized controlled trial. Ten patients were randomly assigned to the placebo group and 10 to the ISDN group, who received 40 mg sustained release isosorbide dinitrate. Haemodynamic variables were measured before treatment, after 0.5 and 1 h and then every 2 hours up to the 8th hour after treatment. There was no significant change in any haemodynamic parameter in the placebo group, during the study period. In the ISDN group there was a significant fall in pulmonary artery diastolic pressure at 4 and 8 h, from 19.0 +/- 1.0 mm Hg to 16.5 +/- 1.2 mm Hg and 15.5 +/- 0.8 mmHg, respectively. The mean pulmonary capillary wedge pressure fell progressively from 17.9 +/- 1.0 to 12.5 +/- 1.2 mmHg at 2 h (p less than 0.001 in comparison with the placebo group. The fall remained significant up to 8 h. There was no statistically significant change in heart rate, cardiac index, systemic blood pressure or systemic and pulmonary vascular resistances. On the whole the cardiac index remained unchanged. There were numerous individual variations of cardiac index in relation to the initial mean pulmonary capillary wedge pressure and the magnitude of its fall following administration of ISDN. The change in cardiac index was inversely correlated with the control cardiac index (r = -0.69, p less than 0.02).

Delayed-Action Preparations↗

Synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines and their actions at adrenoceptors in vivo and in vitro.

An improved synthesis of 1-(aminomethyl)-1,2,3,4-tetrahydroisoquinolines has been developed by using aluminum hydride reduction of 1-cyano-1,2,3,4-tetrahydroisoquinolines. Three 1-(aminomethyl)-6,7-dihydroxytetrahydroisoquinolines were tested for actions at beta adrenoceptors in order to examine a proposed similarity between this series and the related phenylethanolamines. The aminomethyl, (isopropylamino)methyl, and (tert-butylamino)methyl derivatives all showed weak partial agonist activity at beta adrenoceptors and the first also showed weak alpha adrenoceptor agonist activity in vivo. Their low potency implies that the catechol group of THIQ sympathomimetics, such as trimetoquinol, binds differently from that of the natural catecholamines. The protonation behavior of representative aminomethyl-THIQ's was investigated by pKa measurement and 1H and 13C NMR, and the compounds were shown to be substantially monoprotonated, on the exocyclic nitrogen, at physiological pH.

Animals↗

[8-hour hemodynamic study of 2 sustained-release nitrate derivatives. Comparative double-blind study against placebo].

The aim of this study was to evaluate the duration of the hemodynamic effects of a new slow release preparation of isosorbide dinitrate and to compare its action with placebo and a slow release nitroglycerin preparation whose hemodynamic efficacity has already been demonstrated. The study was undertaken in 30 patients admitted to the intensive care unit during the acute phase of myocardial infarction complicated by left ventricular failure less than 12 hours after the onset of the chest pain. The patient population was uniform: 24 males, 6 females, mean age 61 years. Fifteen patients had anterior infarcts and 15 posterior infarcts. The drugs were administered double blind in a randomised fashion to 3 groups of 10 patients, the initial clinical and hemodynamic characteristics of which were comparable: 10 patients received placebo (placebo group); 10 patients received slow release nitroglycerin in a 7,5 mg gelule (NTG group) and 10 patients received 40 mg slow release isosorbide dinitrate (ISDN group). The following parameters were compared: heart rate, right atrial pressure, pulmonary artery and capillary pressures, systemic arterial pressure, cardiac index and systemic and pulmonary arterial resistances. These parameters were measured before therapy, half an hour, one hour and every two hours up to the 8th hour after drug administration. All patients were in moderate left ventricular failure with an initial mean capillary pressure of 18 mmHg +/- 1,3 mmHg. In the placebo group, none of the parameters studied changed significantly during the study. Pulmonary artery pressure fell significantly by 11 p. cent in the NTG group and 7,5 p. cent in the ISDN group. Mean pulmonary capillary pressure fell progressively in both treatment groups; the change was significant compared to the placebo group from the first hour for the ISDN group, and from the second hour for the NTG group. The fall remained significant at the 8th hour for the ISDN group but not in the NTG group. Cardiac index, systemic blood pressure, systemic and pulmonary arterial resistances did not change significantly. The cardiac index remained stable in the 30 patients, but with a number of individual variations depending on initial mean pulmonary capillary pressure and the importance of its fall after nitrate administration. The authors conclude that the hemodynamic effects of slow release NTG and ISDN in the acute phase of myocardial infarction complicated by moderate left ventricular failure are comparable. Pulmonary capillary pressure was the hemodynamic parameter which underwent the greatest variation in the two treatment groups. Its fall was more prolonged in the ISDN than in the NTG group.

Administration, Oral↗

Gallium-67 in the evaluation of sarcoidosis: correlations with serum angiotensin-converting enzyme and bronchoalveolar lavage.

Gallium-67 (67Ga) scanning was assessed for its usefulness in the evaluation and follow-up of 54 patients with sarcoidosis, both treated and untreated. Scans were repeated in 23 subjects. Serum levels of angiotensin-converting enzyme (ACE) were determined concurrently in all 54 patients and bronchoalveolar lavage was performed in 29 patients. Gallium-67 scan was effective in the detection and assessment of lesions not revealed by traditional methods of investigation, particularly those affecting the mediastinum, spleen, and salivary glands. The scan also enabled fibrotic lesions, which do not show uptake, to be distinguished from granulomatous lesions, which do--an advantage of prognostic interest particularly in patients with pulmonary lesions. Another merit of 67Ga scanning was that it offered a means of following disease progression in each site. In patients showing spontaneous clearing of disease or receiving treatment the scintigraphic method was more sensitive than serum ACE determination. Scan findings showed a rough correlation with serum ACE but not with bronchoalveolar lavage findings. This suggests that the three markers probably reflect different stages of the granulomatous process. On the strength of this study the indications for gallium scanning in sarcoid patients can be defined more clearly than has previously been possible.

Adolescent↗

[Serum level of angiotensin-converting enzyme in sarcoidosis. Attempted correlation with the clinical activity of the disease (author's transl)].

Serum levels of angiotensin-converting enzyme (ACE) were measured in 111 healthy subjects and in 117 adult patients with mediastinal and pulmonary sarcoidosis. The patients were followed up for 3 years. Detailed clinical investigations and ACE level measurements were performed every three months. The activity of the disease was assessed in 94 patients without treatment and in 23 patients under corticosteroid therapy. Mean ACE levels were significantly higher (p less than 0,0001) in all patients with sarcoidosis than in controls. They were also high (greater than 35 units/ml) in 32 patients with active forms of the disease. In 19 patients with inactive forms ACE levels were either moderately raised on normal, while considerable variations were observed in those with stable, persistent sarcoidosis. Complete spontaneous or therapeutically induced remission were accompanied by a return of ACE to normal values, but this was not the case for incomplete remission. There was no correlation between ACE levels and the radiological stages of the disease. Measuring ACE levels in patients with sarcoidosis may therefore contribute to diagnosis and surveillance and help to distinguish between complete and incomplete remissions.

Adolescent↗

[Evidence of junctional complexes between cells of monocytic origin in sarcoid granulomas (author's transl)].

Ultrastructural studies of lung and lymph nodes biopsies from twelve patients with sarcoidosis were performed. They consistently demonstrated junctional complexes between consistently demonstrated junctional complexes between granulomatous cells issued from the mononuclear phagocyte system. These inter-cellular contacts have a desmosome-like appearance but differ in some of their structural aspects. The role of these complexes appearing between cells of monocytic origin remains to be defined.

Granuloma↗

[Alveolar proteinosis and acute leucosis. One observation (author's transl)].

The authors observed a pulmonary alvelolar proteinosis in an 11 years old child with acute leucosis. They underlined the exceptional character of this association in a child, while it is known in the adult and almost always with a bad prognosis. A dysimmunity context linked to a hematological disease and/or its treatment, is favoured among the pathogenic hypotheses.

Child↗

Vigabatrin in the treatment of childhood epilepsies: a single-blind placebo-controlled study.

Sixty-one pediatric patients (12-229 months of age) with refractory epilepsy were treated with vigabatrin [gamma-vinyl GABA (GVG)] in a 16-week, single-blind, add-on, placebo-controlled trial. Twenty-three patients (38%) showed a reduction of more than 50% in seizure frequency; 12 patients (20%) experienced a seizure increase; and the remaining 26 did not show significant differences between placebo and GVG treatment. Among the 216 patients who entered the long-term phase after having experienced more than 50% decrease in seizure frequency, 14 continued with the same degree of improvement after 2-11 months of follow-up (mean 7.7). GVG was particularly efficient in cryptogenic partial epilepsy. Conversely, nonprogressive myoclonic epilepsy tended to be aggravated. Agitation was the most commonly observed side effect, mainly at onset of therapy in mentally retarded patients, but was easily reversed by dose reduction. GVG is a promising drug in the treatment of refractory epilepsies of childhood.

4-Aminobutyrate Transaminase↗

Multi-centre double-blind comparison of terfenadine once daily versus twice daily in patients with hay fever.

This double-blind, randomized multi-centre study was designed to compare efficacy and tolerability of 120 mg terfenadine taken once daily (in the morning) with the established regimen of 60 mg terfenadine taken twice daily in the treatment of seasonal rhinitis. Two comparable groups, a total of 191 hay fever patients, were treated for 1 week. Symptom severity was assessed by the investigators before and at the end of the treatment (visual analogue scale), and daily by the patient (four-point rating scale). All symptoms improved to a similar degree in both groups. Differences between the two groups were not statistically significant, except for nasal symptoms in three cases as assessed by the visual analogue scale in one centre (better relief in the group given 120 mg terfenadine once daily). Tolerability was good and similar in both groups. The data presented show that in the treatment of hay fever 120 mg terfenadine given once daily is an effective, convenient and well tolerated alternative to the regimen of 60 mg terfenadine given twice daily.

Adult↗