Antihypertensive efficacy and safe use of once-daily sustained-release diltiazem in the elderly: a comparison with captopril. The Dilcacomp Study Group.

The efficacy and safety of sustained-release diltiazem, 200-300 mg once daily was compared with that of captopril, 12.5-25 mg twice-daily, in 100 elderly patients (65-85 years old) with mild to moderate essential hypertension (supine diastolic blood pressure 95-115 mmHg). All patients received placebo for 2 weeks, followed by an 8-week double-blind period, and were randomized to either diltiazem (n = 50) or captopril (n = 50). Their blood pressure was measured at trough level at week 4 immediately before dosing, i.e. 24 h post diltiazem dose or 12 h post captopril dose. Also at week 4, in non-responders, diltiazem was increased from 200 to 300 mg once daily and captopril from 12.5 to 25 mg twice daily to achieve a target supine diastolic blood pressure reduction of at least 10 mmHg or a diastolic blood pressure below 90 mmHg. Supine diastolic blood pressure, at week 8, was significantly (P < 0.001) reduced from 102 +/- 1 to 90 +/- 1 mmHg with diltiazem and from 103 +/- 1 to 89 +/- 1 mmHg with captopril, bringing this parameter within normal limits for both groups. Supine systolic blood pressure was also significantly (P < 0.001) reduced. Target blood pressure was achieved in 68% of patients taking diltiazem and in 70% taking captopril. Distribution of adverse events was comparable in both groups; no significant changes in laboratory or electrocardiographic parameters occurred. Two serious events were reported with captopril: one sudden death and one cerebrovascular stroke. Sustained-release diltiazem once a day is a convenient, well tolerated, first line treatment for hypertension in the elderly, for whom the possibility of using two dose levels allows a close regimen adjustment, 200 mg being recommended as a starting dose.

Efficacy and safety of the 200-300 mg sustained release formulation of diltiazem administered once daily in patients with stable angina.

The aim of this multicentre randomised double blind study was to compare the efficacy and safety of the 200-300 mg sustained release diltiazem formulation administered once daily (200-300 SR) with standard diltiazem (D) given three or four times daily to patients with stable angina. Patients aged 59 years, with a reproducible exercise test on placebo, were randomised to 4 weeks of treatment with 200-300 SR (n = 70) or D (n = 74). The initial dosage was 200 mg in the 200-300 SR group and 60 mg t.i.d. in the D group, increased to 300 mg once daily or 60 mg q.i.d., respectively, if ergometric parameters, which were always measured at the end of the dosing period, had not improved after two weeks. After 4 weeks of treatment, the antianginal efficacy at rest was comparable in the 200-300 SR and the D group; there was a prolongation of the total duration of exertion of 14% and 18% respectively (P < 0.01 vs placebo for both groups with no intergroup difference). A dose-effect relation was found with both formulations. The 200-300 SR formulation gave full 24 hour anti-ischaemic protection when administered once daily. Its efficacy and safety were comparable to those of standard diltiazem t.i.d. or q.i.d. in patients with stable angina. The once daily administration should improve treatment compliance.

Acute effects of zolpidem, triazolam and flunitrazepam on arterial blood gases and control of breathing in severe COPD.

Patients with severe chronic obstructive pulmonary disease (COPD) commonly complain of insomnia, but hypnotic drugs are generally not recommended due to their depressant effect on the respiratory centres. The aim of this study was, therefore, to compare the effects of a single dose of the benzodiazepine hypnotics, triazolam 0.25 mg and flunitrazepam 1 mg, and a new imidazopyridine compound, zolpidem 10 mg, in hypercapnic COPD patients. Twelve stable COPD patients (mean +/- SD arterial oxygen tension (PaO2) 9.3 +/- 0.8 kPa and arterial carbon dioxide tension (PaCO2) 5.9 +/- 1.9 kPa) were included in the study. The following measurements were performed before and 2 h after drug administration: PaO2 and PaCO2, minute ventilation (VE), mouth occlusion pressure (P0.1), rebreathing CO2 tests with ventilatory response to carbon dioxide stimulation (delta VE/delta PACO2) and mouth occlusion pressure response to carbon dioxide stimulation (delta P0.1/delta PACO2). The measurements were performed in a randomized, double-blind fashion, each patient receiving a single dose of each drug on three different days, separated by a one week interval. No difference was noted between control measurements and those taken 2 h after administration of zolpidem in the following parameters: PaCO2, PaCO2, VE, P0.1, delta VE/delta PACO2 and delta P0.1/PACO2. Two hours after administration of triazolam and flunitrazepam, a significant difference was noted in VE for triazolam and for flunitrazepam. After flunitrazepam administration, a significant decrease in PaCO2 (6 +/- 1.8 at baseline versus 7 +/- 0.4 kPa), and delta VE/PACO2 (0.44 +/- 0.20 at baseline versus 0.31 +/- 0.21 l.min-1 x kPa) were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Bladder-neck opening test in spinal cord injury patients using a new i.v. alpha-blocking agent, alfuzosin.

A bladder-neck opening test using alfuzosin, a new alpha-adrenoceptor blocking agent, was carried out in 21 patients with spinal cord injury. The efficacy of alfuzosin was assessed with 4 simple urodynamic parameters: micturition, residual urine, posterior urethral pressure and diameter. Both mean urethral pressure and diameter were significantly affected after the administration of 5 mg i.v. alfuzosin. The test was clinically positive in 18 patients: 11 out of 13 patients using intermittent catheterisation or continuous drainage urinated and 6 out of 8 patients already tapping had reduced residual urine volumes. A decrease in posterior urethral pressure was also observed in 2 out of 3 patients who did not respond clinically to alfuzosin. Alfuzosin was well tolerated during this test. Oral alfuzosin should therefore be investigated in patients who gave a satisfactory response to such a test.

[Hemodynamic effects at rest and exertion of a new partial beta-agonist (cicloprolol) in moderated cardiac failure]. / Effets hémodynamiques au repos et à l'effort d'un nouvel agent bêta-agoniste partiel (cicloprolol) dans l'insuffisance cardiaque modérée.

The haemodynamic effects of cicloprolol, a new partial beta 1-adrenoceptor agonist, were investigated at rest and during exercise in 10 patients with moderate heart failure. At rest, cicloprolol (0.10 mg/kg i.v.) increased heart rate by 8 p. 100 (80.6 +/- 5.7 vs 74.7 +/- 11.9 beats/min; p less than 0.05), cardiac index by 17 p. 100 (3.74 +/- 0.57 vs 3.20 +/- 0.41 l/min/m2; p less than 0.001) and stroke index by 6 p. 100 (46.3 +/- 8.3 vs 43.7 +/- 8.8 ml/beat/m2; p less than 0.05). Left ventricular end-diastolic pressure was reduced by 35 p. 100 (9.9 +/- 5.0 vs 15.2 +/- 7.4 mmHg; p less than 0.01). There were no significant changes in aortic pressure. Systemic vascular resistance decreased by 15 p. 100 (1,030.8 +/- 234.6 vs 1,209.6 +/- 319.7 dynes.s.cm-5; p less than 0.01). During moderate exercise (114 +/- 13 watts) in supine position, cicloprolol induced a 10 p. 100 reduction of tachycardia (99.7 +/- 10.2 vs 112.2 +/- 16.5 beats/min; p less than 0.01), a 6 p. 100 decrease of mean aortic pressure (112.4 +/- 19.7 vs 119.5 +/- 19.2 mmHg; p less than 0.01) and an 8 p. 100 decrease of cardiac index (5.42 +/- 0.63 vs 5.88 +/- 0.75 l/min/m2; p less than 0.001). There were no significant changes in left ventricular filling pressure and stroke index. When data obtained at rest and during exercise were pooled, an inverse linear relationship (p less than 0.01) was found between heart rate before treatment with cicloprolol and cicloprolol-induced variations in heart rate and cardiac index.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial failure during Yersinia enterocolitica infection.

A case of severe cardiac failure during generalized Yersinia enterocolitica infection, in a previously healthy woman is described. It was possible to demonstrate the important role of coronary hypoperfusion in the late stages of septic shock. When beta stimulant drugs became ineffective, IABP improved cardiac function.

[Consequences of continuous positive airway pressure (CPAP) on left ventricular function. Assessment by M-mode echocardiography (author's transl)]. / Effets de la ventilation spontanée en pression positive permanente (CPAP) sur la fonction ventriculaire gauche. Appréciation par échographie en mode M.

The consequences of continuous positive airway pressure (CPAP) on left ventricular function are uncertain. Left ventricular function was assessed by M-mode echocardiography in 8 young normal subjects during CPAP via face mask. Heart rate and arterial pressure did not change. End-diastolic volume and stroke volume significantly decreased. Ejection fraction remained unchanged. The slight decrease of stroke volume induced by increasing positive airway pressure is in relation to decreased left ventricular preload.

[Starr-Edwards mitral valve prosthesis and secondary clinical deterioration. Hemodynamic study in 14 patients]. / Prothèse de Starr-Edwards mitrale et aggravation clinique secondaire. Etude hémodynamique de 14 malades.

The haemodynamic and angiocardiographic data of 19 patients with Starr-Edwards mitral valve prosthesis were analysed to determine the causes of secondary deterioration observed in 14 of them. This was shown to be due to: 1. Surgical complications or progression of pre-existing valvular lesions which were not, or only partially, corrected (3 cases) (adiastole due to pericardial effusion, aortic valve disease and severe tricuspid incompetence); average diastolic pressure gradient CPW-LV 4.7 +/- 1.5 mmHG, the functional valve surface area (FVA) 1.37 +/- 0.2 cm2, LVEDP 17.7 +/- 4 mmHg, LVEDV 57.5 +/- 11 ml/m2, and EF 73.5 +/- 8 p. 100; 2. Deterioration of left ventricular contractility with LVEDP greater than 13 mmHg, LVEDV greater than 100 ml/m2 and EF less than 45 p. 100 (4 cases); CPW-LV gradient 9.8 +/- 4 mmHG, FVSA 1.30 +/- 0.2 cm2, LVEDP 20.5 +/- 8 mmHG, LVEDV 212 +/- 168 ml and EF 38 +/- 21 p. 100; 3. Significant reduction of left ventricular volume (LVEDV 22 ml/m2 1 case); 4. Left atrial thrombosis (1 case); 5. Prosthetic valve dysfunction (5 cases) one paravalvular leak and 4 thromboses. In these 4 cases, the PCW-LV gradient was 15 +/- 5 mmHg, FVSA 0.95 +/- 0.1 cm2 LVEDP 8 +/- 2 mmHg, LVEDV 132.8 +/- 93 ml/m2 and EF 45 +/- 28 p. 100; these results were different to whose found in the other patients and those investigated systematically (PCW-LV gradient 8.2 +/- 3 mmHg, FVSA 1.38 +/- 0.3 cm2, LVEDP 11 +/- 4 mmHg, LVEDV 66.4 +/- 33 ml/m2, EF 53 +/- 13 p. 100). The significant haemodynamic criteria in favour of thrombosis of the prosthesis were: CPW-LV gradient greater than 12 mmHg under basal conditions or after exercise and a FVSA less than 1.1 cm2.

[Severe forms of imported malaria concerning three pernicious attacks and a black water fever (hemoglobinuria) (author's transl)]. / Formes graves du paludisme d'importation a propos de trois accès pernicieux et d'une fièvre bilieuse hémoglobinurique.

Four severe cases of imported malaria are reported here. Three of them are pernicious and the fourth is a black water fever (hemoglobinuria). The difficulties of initial diagnosis are exposed. There was no mortality in these four cases which represent the annual recruiting of a multipurpose intensive care unit. But the complications are severe in contradiction with easy effective chemoprophylaxis. The principles of treatment and prophylaxis are resumed in the light of these four observations.

[Late thrombosis of mitral valve prosthesis in 27 cases]. / Thromboses tardives sur prothèses mitrales a propos de 27 observations.

Twenty seven cases of late thrombosis of ball and floating or tilting disc prostheses were studied. All patients were on anticoagulant therapy which appeared to be well adapted in 33% patients. Signs suggestive of thrombosis were inconsistant and the diagnosis was made on the association of severl of the following features: -- systemic embolism (44%); -- radiographic signs of left ventricular failure (51%); -- absence of opening click, variable A2 -- opening click intervals, apparition or aggravation of a systolic regurgitant murmur or a distolic murmur suggestive of obstruction on the phonocardiogramme; -- delayed opening of the mobile component or the presence of abnormal echos between the ball and anterior cage echo on the echocardiogramme; -- a gradient of over 12 mmHg across the prosthesis. An isolated episode of systemic embolism when the rest of the work-up is negative may be managed by the addition of a platelet antiaggregant and reinforcement of the anticoagulant therapy; further investigaton is advisable in the face of progressive symptoms. Fibrinolytic treatment and/or surgery is justified when systemic emboli recur or if the work-up is positive.