Irreversible H2-antagonism of the four isomeric butyl analogues of mifentidine.

It has been hypothesized that bidentate hydrogen bonding plays an important role in the interaction of imidazolylphenylformamidines with the H2-receptor. The present study, in which the degree of pseudo-irreversible H2-antagonism of the four isomeric butyl substituted mifentidine analogues was determined on the spontaneously beating right atrium of the male guinea-pig, lends further support to this hypothesis. In solution the EE/EZ ratio is different for the four isomeric butylated mifentidine analogues. The rank order of the percentage of E,E conformation, which favors a bidentate interaction, of the formamidine moiety parallels the rank order of pseudo-irreversible H2-antagonism.

Alterations in thyroid function induced by chronic administration of amiodarone.

Thyroid function alterations induced by amiodarone treatment (200-400 mg/day for 5 days/week) were studied in 50 patients with heart disease (age 34-75 years, mean age 55.5 +/- 11.8) for 25.6 +/- 15.0 months. Statistical analysis was made of the results obtained from the 14 patients who underwent all of the schedule examinations during the same 16-month period. A reduction in T3 was observed after 7 days' treatment; this became statistically significant at 12 and 16 months. FT3 fell significantly only after 7 days; rT3 showed an opposite trend to that of T3 (low T3 syndrome), with significant increases at all observation times. TSH rose at 7 days, then fell gradually to below baseline values after 12 months. No evidence of clinical hyperthyroidism accompanied the significant increases of T4 and FT4 observed at 1, 3, 6, and 16 months; when this complication occurred (in 6% of the cases) it was associated with a rise or lack of reduction in T3 levels. In these cases treatment was withdrawn. Amiodarone was also discontinued in 2 other cases (4%) with elevated thyroid function indices but without clinical symptoms. Seven patients who showed an isolated increase of FT3 were carefully monitored; only in one case did clinical hyperthyroidism develop with a simultaneous rise in the T3 level. A diagnosis of hypothyroidism may be considered only if there is a reduction in T4 levels, since an isolated increase in TSH is not as reliable; treatment had to be suspended for this reason in 2 cases (4%), both without clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atrial septal defect of the ostium secundum associated with incomplete left bundle branch block]. / Difetto del setto interatriale tipo "ostium secundum" associato a blocco di branca sinistra incompleto.

The ECG in Ostium Secundum Atrial Septal Defect (O.S. ASD) shows typically a pattern of incomplete right bundle branch block with right axis deviation and a 12 year old boy suspected of having O.S. ASD on the basis of x-ray and echocardiographic findings showed an ECG pattern of incomplete left bundle branch block. Physical examination and a phonocardiogram revealed a single second heart sound. An ECG recorded at age five showed a typical pattern consistent with O.S. ASD. The angiographic examination confirmed the suggested diagnosis. This is, to our knowledge, the first case of O.S. ASD with incomplete left bundle branch block. The conduction disorder may have abolished the fixed splitting of the second heart sound.