[Clinical case of the month. Triple valvular dysfunction associated with long-term ergotamine therapy]. / Le cas clinique du mois. Insuffisance trivalvulaire associée à l'utilisation chronique d'ergotamine.

We report the case of a 48-year-old woman who present a tricuspid, mitral and aortic regurgitation after long term ingestion of ergot alkaloids. Tricuspid and mitral fibrosis associated with retraction of the aortic leaflets are the causes of heart failure. Replacement of the three valves will be necessary. This is one, not the least complication of long-term ergotamine therapy.

Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive heart failure (MERIT-HF). MERIT-HF Study Group.

CONTEXT: Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.

Cibenzoline in the prevention of recurrence of supraventricular arrhythmias.

Hundred and twenty-three outpatients were treated with oral cibenzoline for 3 months in order to test the efficacy and safety of the compound in the prevention of the recurrence of supraventricular arrhythmias. The dose was 260-390 mg/day for those under 70 and 130-260 mg/day for those over 70 years. All patients were converted to sinus rhythm before entry to the study and 95 patients had previously been treated with one or more drugs which had been discontinued due to lack of effect and/or poor tolerability. In 21 patients (17%) recurrence was documented by ECG or Holter monitoring, cibenzoline thus being effective in 83%. In 35 other patients there was a return of symptoms but no confirmation of recurrence. There were no relevant changes in blood pressure or heart rate. PR, QT and QTc intervals were stable but mean QRS interval increased slightly during the first week before stabilizing. Cibenzoline was discontinued because of adverse events in only 10 patients (8.1%). The most frequent complaints were nausea, vertigo and faintness. Seventy-two per cent of patients rated their well-being as "well/very well" at month one compared with 84% at month three. Cibenzoline is an appropriate first line choice in this indication.

Intrathoracic infections with bacteraemia due to Eikenella corrodens as a complication of peritonsillar abscesses: report of a case and review of the literature.

A 52-year-old man, without previous disease, presented with dysphagia, dyspnoea, high fever and sore throat after peritonsillar abscesses drainage. Physical and complementary examinations were consistent with pericarditis, mediastinitis, pneumonia and pleuritis. Blood cultures grew Eikenella corrodens resistant to clindamycin and amikacin. We emphasize the pathogenic potential of Eikenella corrodens. To the best of our knowledge, this is the first reported case of this organism as a pathogen in intrathoracic infections after peritonsillar abscesses drainage.

[Effects of sotalol on blocked suprahepatic pressure in cirrhotic patients]. / Effets du sotalol sur la pression sus-hépatique bloquée de malades cirrhotiques.

With the use of two balloon catheters inserted in the right jugular vein, the following parameters were measured before and after injection of sotalol (1.5 mg/kg): cardiac output with the thermodilution method, hepatic output with the indocyanin green perfusion method, free sub-hepatic pressure, blocked sub-hepatic pressure recorded at rest and during coughing. After 30 minutes, the following modifications were recorded: the cardiac output goes from 6.8 +/- 2.1 to 5.9 +/- 1.9 L/min (NS), the hepatic output goes from 1.9 +/- 1.1 to 1.5 +/- 0.6 L/min (NS), the hepatic pressure gradient goes from 18.2 +/- 6.1 to 11.5 +/- 5.4 mmHg (p less than or equal to 0.0005); the blocked sus-hepatic pressure at rest goes from 25.0 +/- 7.8 to 19.8 +/- 8.0 mmHg (p less than or equal to 0.025); the blocked sus-hepatic pressure during coughing goes from 92 +/- 32 to 82 +/- 39 mmHg (NS). This study demonstrates: a) that the drop in the hepatic pressure gradient induced by a dose of sotalol is more important than that observed by Westaby et al. with propranolol: 37% vs 31% (NS); b) that sotalol cannot lower the blocked sub-hepatic pressure during coughing. This result suggests that the potential protective effect of sotalol toward esophageal varices rupture disappears during coughing.

[The role of plasma alpha 1-glycoprotein acid in the binding of aminopyrine]. / Rôle de l' alpha 1-glycoprotéine acide plasmatique dans la fixation de l'aminopyrine.

Under certain pathological conditions the binding of various substances by serum proteins is altered. The plasma concentrations of alpha 1-acid glycoprotein, also known as orosomucoid are reported to be elevated in stressful situation and in certain disease states like acute myocardial infarction. The binding of aminopyrine to serum proteins and alpha 1-acid glycoprotein was determined using equilibrium dialysis. It appears that alpha 1-acid glycoprotein has specific binding sites for aminopyrine. Aminopyrine was also bound to other serum proteins. On addition the results indicate that an increase of alpha 1-acid glycoprotein to concentrations such as those seen in some pathological states does not really alter the percent of aminopyrine bind to serum proteins.

Serum creatine kinase isoenzyme MB concentration after endomyocardial biopsy.

Serum total creatine kinase (CK), CK-MB and myoglobin (Mb) were serially determined in 17 patients who underwent endomyocardial biopsy. Mean total CK levels increased from 36 +/- 27 U/l 30 min before biopsy to a maximum of 112 +/- 77 U/l 8 h following the procedure (p less than 0.05). Similarly, Mb concentrations rose from 57 +/- 55 micrograms/l to 119 +/- 57 micrograms/l 30 min after biopsy (p less than 0.05). Normalization of total CK and Mb levels occurred within 16 and 8 h, respectively. A new immunoenzymetric assay (IEMA) was used to measure the mass concentration of the CK-MB molecule. The initial CK-MB levels were 0.2 +/- 0.4 microgram/l; a small but significant elevation was recorded as early as 2 h after biopsy (1.6 +/- 1.5 micrograms/l, p less than 0.05). CK-MB returned to initial concentration 16 h after the beginning of the procedure. Comparison with the maximum CK-MB levels recorded in 16 myocardial infarction patients (258 +/- 172 micrograms/l, range 90-680 micrograms/l) indicated that the modest increase of CK-MB level detected after biopsy probably reflects a limited endomyocardium lesion at the sampling site, excluding any significant myocardial damage. Total CK and Mb, which showed more pronounced elevations than CK-MB, are likely to originate from other sources than the myocardium.

Cardiac tamponade as the first manifestation of cardiothoracic malignancy: a study of 10 cases.

Ten patients with cardiac tamponade as the first presentation of cardiothoracic malignancy were evaluated from May, 1976 to June, 1982. The best treatment of this particularly rare neoplastic manifestation is still being debated. The clinical data of our ten patients were compared to those previously described in the literature. They were first treated by pericardiocentesis and creation of a pericardial window, without recurrence of significant pericardial effusion. Our data suggest that the addition of radiotherapy to the other therapeutic methods (surgery and chemotherapy) may improve survival.

Differentiating muscle damage from myocardial injury by means of the serum creatine kinase (CK) isoenzyme MB mass measurement/total CK activity ratio.

We immunoenzymometrically measured creatine kinase (CK) isoenzyme MB in extracts of myocardium and in homogenates of five different skeletal muscles. CK-MB concentrations in the former averaged 80.9 micrograms/g wet tissue; in the skeletal muscles it varied widely, being (e.g.) 25-fold greater in diaphragm than in psoas. CK-MB in skeletal muscles ranged from 0.9 to 44 ng/U of total CK; the mean for myocardium was 202 ng/U. In sera from 10 trauma and 36 burn patients without myocardial involvement, maximum ratios for CK-MB mass/total CK activity averaged 7 (SEM 1) ng/U and 18 (SEM 6) ng/U, respectively. Except for an infant (220 ng/U), the highest ratio we found for serum after muscular damage was 38 ng/U. In contrast, the mean maximum ratio determined in 23 cases of acute myocardial infarction exceeded 200 ng/U. Among seven determinations performed 8 to 32 h after onset of symptoms, each infarct patient demonstrated at least one ratio greater than or equal to 110 ng/U. Ratios observed after infarct were unrelated to treatment received during the acute phase. We propose a CK-MB/total CK ratio of 80 ng/U as the cutoff value for differentiating myocardial necrosis from muscular injury.

[The effect of sotalol on cirrhotic portal hypertension. Results of a preliminary study of cardiac and hepatic hemodynamics]. / Effet du sotalol sur l'hypertension portale du cirrhotique. Résultats préliminaires d'une étude hémodynamique cardiaque et hépatique.

Using two balloon-tipped flotation catheters introduced through the jugular vein, systemic and hepatic hemodynamic measurements were made in nine cirrhotic patients before and 15, 30, 45 and 60 minutes after intravenous injection of 1.5 mg/kg of sotalol. At 30 minutes, the occluded sus-hepatic pressure fell from 23.6 +/- 6.4 mm Hg to 16.7 +/- 5.7 mm Hg (P less than 0.025); the sus-hepatic pressure gradient decreased from 16.2 +/- 3.8 mm Hg to 8.1 +/- 2.7 mm Hg (P less than 0.0005) whereas cardiac output failed to show any significant change (6.8 +/- 2.4 l/minute prior to drug versus 5.7 +/- 2.1 l/minute). These results suggest that sotalol, a non selective beta-adrenoceptor blocking drug with weaker negative inotropic effects than propranolol is effective in lowering portal pressure. The decrease of the sus-hepatic pressure gradient induced by the dose we used (50.2 +/- 20.0%) is statistically greater than that observed by Westaby et al. with intravenous propranolol (31.0 +/- 8.2%). The absence of hepatic metabolism of the drug which is excreted untransformed by the kidney should facilitate the selection of the optimal oral dose. The rather long half-life should also allow administration of one single daily dose which improves patients' compliance. The long term oral efficacy remains to be demonstrated in further studies, but in view of the advantages that sotalol possesses over propranolol, these studies are deemed justified.

Effects of age on the pharmacokinetics of mexiletine.

Mexiletine (1-methyl-2-(2, 6-xylyloxy)ethylamine hydrochloride) is an antiarrhythmic drug eliminated primarily by hepatic metabolism. The influence of age on the plasma pharmacokinetics of mexiletine was assessed in seven young and ten elderly healthy subjects. Mexiletine (50 mg) was administered orally three times daily for 10 days. The use of low doses of mexiletine was possible owing to the development of a new fluorescence high performance liquid chromatography method with a limit of sensitivity lower than 20 ng/ml. No differences in the pharmacokinetic parameters of mexiletine related to age were observed. At steady-state plasma concentrations were 0.121 +/- 0.033 microgram-ml in the young volunteers, and 0.135 +/- 0.150 microgram/ml in the older subjects. The elimination t 1/2 was 11.4 +/- 1.78 h in the young subjects and 10.48 +/- 3.06 h in the elderly. The data provide no justification for lowering the recommended dose of mexiletine for older patients.

Lack of defective cardiac oxidative metabolism in intact dogs subjected to a prolonged low-dose infusion of Escherichia coli endotoxin.

The aim of the present study was to determine possible direct adverse effects of a 2-hour Escherichia coli endotoxin infusion (50 ng kg-1 min-1) on myocardial oxidative carbohydrate metabolism. The experiments were performed in intact dogs to assay glucose and lactate cardiac uptake and relate them to oxygen consumption (MVO2), CO2 production, and myocardial hemodynamics. Coronary sinus blood flow (CSBF) was measured by thermodilution, and the arteriovenous differences in glucose, lactate, pyruvate, O2, and CO2 were determined by blood samples obtained simultaneously from the carotid artery and sinus coronary. The adequacy of CSBF in meeting cardiac oxygen needs was evaluated by calculating the percentage of anaerobic metabolic rate (% AMR). During endotoxin infusion, CSBF was significantly lowered by 33% while mean aortic blood pressure was decreased by 43%. Cardiac index exhibited a minimal reduction of 14%. Mean arterial blood glucose decreased 30% and arterial lactate increased 100%. Despite the progressively developing hypoglycemia, cardiac glucose uptake increased 140%. Although MVO2 was reduced to 70% of control value, lactate uptake increased 50%. Throughout the experimental period, the % AMR remained negative. Under endotoxin infusion, up to 78% of the cardiac CO2 production was derived from carbohydrate utilization, as compared to 40% prior to endotoxin infusion. Our findings suggest the absence of any toxic action by an endotoxin-sustained infusion on cardiac oxidative metabolism.

Hemodynamic effects of nifedipine on secondary pulmonary hypertension in man.

We evaluated the hemodynamic effects of the calcium antagonist nifedipine in 13 consecutive patients admitted to the intensive care unit with secondary pulmonary hypertension. Etiology of secondary pulmonary hypertension was: chronic obstructive pulmonary disease (n = 9), pulmonary emboli (n = 2), pulmonary fibrosis (n = 2). We obtained the resting hemodynamic parameters before, and 60, 120, 180 minutes after the sublingual administration of nifedipine 20 mg. All patients had normal pulmonary artery wedge pressure before nifedipine. After 60 minutes, systolic pulmonary artery pressure fell from 72.3 +/- 7 to 57.3 +/- 5.4 mm Hg (p less than 0.005) and mean pulmonary artery pressure from 44.6 +/- 4.0 to 33.6 +/- 3.2 mm Hg (p less than 0.001). Cardiac output rose from 6.36 +/- 0.56 to 7.65 +/- 0.64 l/min (p less than 0.005). The pulmonary vascular resistance fell from 431 +/- 58 to 238 +/- 36 dynes. sec. cm-5 (p less than 0.001). Heart rate, mean systemic arterial pressure, pulmonary artery wedge pressure, total systemic vascular resistance and arterial partial pressure of O2 (PaO2) remained unchanged. In this heterogenous population we were unable to reproduce the results of other authors, showing a correlation between PaO2 and fall of pulmonary vascular resistance. These findings confirm the pulmonary vasodilating effect of nifedipine in patients with secondary pulmonary hypertension.

The use of low doses of dopamine in intensive care medicine.

The dopamine alpha- and beta-adrenoceptor dose-response curves are investigated in four patients who are exempt from cardiovascular disease. A dose-related increase in CO, HR and SV is observed with infusion rates of up to 3 micrograms kg-1 min-1. With concentrations greater than 10 micrograms kg-1 min-1, both BP and SVR increase. Low-dose dopamine infusion less than 3 micrograms kg-1 min-1 is investigated in ten other patients. With this infusion rate, a selective renal vasodilation is induced without peripheral or cardiac beta-adrenoceptor activation. Dopamine is responsible for an increase in diuresis FENa, GFR and RBF. These properties are indicated in renal failure, and when haemodynamic support is required in cardiac failure, if an infusion rate of up to 10 micrograms kg-1 min-1 is able to reverse cardiac insufficiency.

Combined haemodynamic effects of low doses of dopamine and dobutamine in patients with acute infarction and cardiac failure.

The haemodynamic effects of an optimal dose of dobutamine (DUo) (6.7 +/- 4.2 micrograms kg-1 min-1) and the combination of this optimal dose minus 2.5 micrograms kg-1 min-1 of dobutamine (DU) plus dopamine 2.5 micrograms kg-1 min-1 (DA) were studied in a first group of 12 consecutive patients with acute myocardial infarction (AMI) and cardiac failure (CF). DUo decreased pulmonary wedge pressure from 23.5 to 16 mm Hg (P less than 0.01), systemic vascular resistance from 1 774 to 1 417 dynes s cm-5 (P less than 0.01). DUo increased cardiac output from 3.21 to 4.55 litres/min (P less than 0.01) and urinary flow (UF) from 20 to 68 ml/h (P less than 0.01). Heart rate and blood pressure did not change significantly. DUo - DU + DA significantly increased UF from 68 to 107 ml/h (P less than 0.05) while the other parameters remained unchanged with respect to DUo. The positive effect of DA on UF was confirmed in a second group of 12 consecutive patients by comparing the successive effects of DA + DUo and DUo + DU : all previously described parameters remained unchanged except UF which decreased from 107 to 65 (P less than 0.01). We conclude that in patients with CF and AMI, association of DA and DUo is useful in obtaining both inotropic and diuretic effects.

The new inotropic phosphodiesterase inhibitors.

Compounds with phosphodiesterase inhibitory activity stimulate myocardial contractility by increasing the intracellular cyclic AMP concentrations. They can also increase Ca2+ entry and inhibit Ca2+ sequestration by the sarcoplasmic reticulum. Xanthines produce bronchodilation with associated venous and arteriolar dilation. However, their use is limited by their positive chronotropic effect and other side effects at high plasma levels. New phosphodiesterase inhibitors have been perfected: they are more specific with little chronotropic effect. Increasing the sensitivity of the myofilaments to Ca2+, and other unclear mechanisms may be involved in the inotropic action of these drugs. These new promising active compounds are described and discussed. They augment cardiac performance and improve regional distribution of blood flow and symptoms. However, their influence on the long-term outcome of severe heart failure has yet to be determined.

[Development of urea, creatinine and creatinine clearance as a function of age and sex]. / Evolution, en fonction de l'âge et du sexe, de l'urée, de la créatinine et de la clairance de la créatinine.

Serum urea and creatinine concentrations were determined in 150 healthy subjects. The formula of Cockcroft and Gault was used in order to calculate creatinine clearance. Such estimation of creatinine clearance is widely used as a parameter for individualization of dosage of drugs secreted primary via the kidneys. The effects of age and sex were then assessed on serum urea, serum creatinine and on creatinine clearance.