In vivo and in vitro percutaneous absorption of [(14)C]di-N-butylphthalate in rat.

This study evaluated the toxicokinetics of [(14)C]di-n-butylphthalate ([(14)C]DBP) after an intravenous administration (1 and 10 mg/kg, in Cremophor) or a topical application (10 microl/cm(2); 10 cm(2), neat) in haired male Sprague-Dawley rats. Additional in vivo and in vitro percutaneous penetration studies of [(14)C]DBP were conducted on male and female haired rats and male hairless rats. After intravenous administration, unchanged DBP disappeared rapidly from the plasma, following a two-exponential function (T1/2beta = 5-7 min). The peak levels of monobutylphthalate (MBP) and its glucuronide conjugate (MBP-Gluc) occurred 1 to 2 and 20 to 30 min after administration, respectively. These metabolites were intensively and rapidly excreted in urine (57% of the dose). However, about 35% of the dose recovered in urine was primarily excreted in bile (mainly as MBP-Gluc) and underwent hepatobiliary recycling. Unchanged DBP was barely detectable in excreta. DBP rapidly penetrated the skin, which constituted a reservoir. The absorption flux determined for 0.5 to 8 and 8 to 48 h of exposure were 43 and 156 microg/cm(2)/h, respectively. The higher flux may be due to radial diffusion of DBP in the stratum and/or epidermis. The in vivo and in vitro experiments revealed that DBP was intensively metabolized into the skin. In vivo percutaneous absorption flux was very similar in male and female haired rats. In contrast, the percutaneous absorption determined in vivo and in vitro was higher in hairless than in haired male rats. Absorption flux was accurately estimated from urinary excretion rate of MBP or MBP-Gluc.

Dipyridamole stress echocardiography and exercise testing for risk stratification after uncomplicated myocardial infarction.

BACKGROUND: Risk stratification for subsequent cardiac events after an acute infarction can be obtained by exercise testing or dipyridamole stress echocardiography. It remains to be determined whether these modalities are equivalent and provide incremental information on top of clinical evaluation. The aim of our study was to compare the prognostic information obtained early after an acute uncomplicated myocardial infarction of high dose dipyridamole coupled with echocardiography (stress echo) or maximal symptom-limited exercise testing. METHODS AND RESULTS: Ninety patients underwent dipyridamole stress echo and exercise testing at a mean +/- SD of 9 +/- 4 days after admission for acute uncomplicated first myocardial infarction. All patients were prospectively followed for 22 +/- 16 months. There were 9 hard events (3 cardiac deaths and 6 acute myocardial infarctions) and 12 soft events due to post MI angina (6 angioplasty and 6 bypass surgery procedures). Univariate predictor of hard events was rest-stress wall motion score index variation (p = 0.009); univariate predictors of all events (hard + soft) were: positive exercise testing (p = 0.001), positive stress echo (p = 0.001), rest-stress wall motion score index variation (p = 0.002), extent of ischemia at echo (p = 0.008). Multivariate analysis by Cox selected a non-Q wave infarction and rest-stress wall motion score index variation as predictors of death or reinfarction (overall chi-square for the model 12.2, p = 0.0022). CONCLUSIONS: Stress echo is superior to ergometric variables for predicting events after uncomplicated myocardial infarction.

[Combined use of bicycle ergometry test and echo-dipyridamole in stratification of risk after thrombolysed myocardial infarct]. / Uso combinato di test al cicloergometro ed eco-dipiridamolo per la stratificazione del rischio dopo infarto miocardico trombolisato.

AIM: Verify the value of the combined use of Dipyridamole Stress Echocardiography (DSE) and Exercise Testing (ET) for predicting cardiac events after Thrombolysed Myocardial Infarction (TMI). STUDY DESIGN: Prospective, with a medium follow-up of 221 days (range 30-446). CLINICAL SETTINGS: Coronary Care Unit with Cardiology Service. PATIENTS: 32 consecutive patients, 24 men and 8 women, mean age 61 years (range 39-72) with acute myocardial infarction. INTERVENTIONS: Systemic thrombolysis with PTPA. DSE and ET in therapeutic wash out 12 +/- 3 days after admission to the Coronary Care Unit. RESULTS: 9 patients had positive ET, 18 patients had negative ET, 5 patients did not perform ET. 19 patients had positive DSE, 13 patients had negative DSE. Patients with positive DSE had in 6 cases (group 1) WMA remote from the infarction area (WMAR), in 13 cases (group 2) WMA appeared in the infarct related area. Cardiac events occurred in 15 patients: 1 cardiovascular death, 1 myocardial re-infarction, 13 cases of unstable angina. 2 patients with negative DSE had cardiac events. All patients in group 1 had events, 1 patient with a previous positive ET, 3 patients with previous negative ET. 2 patients in this group didn't perform ET. 7 patients in group 2 had cardiac events, in all cases with a previous positive ET. 1 single patient in this group with negative ET had events. CONCLUSIONS: 1) Patients without WMA at DSE are at low risk for cardiac events after thrombolysed myocardial infarction. 2) Presence of WMAR appears to be associated with a higher risk, whatever the result of ET may be. 3) Patients without WMAR can be further stratified by ET in therapeutic wash out. High risk patients seem to be those with positive DSE and positive ET. 4) Combined use of DSE and ET seem to allow optimal risk stratification after thrombolysed myocardial infarction.

Relationship between plasma levels of factor VIII related antigen and reticulo-endothelial function in chronic uremia.

The plasma levels of factor VIII related antigen (F VIIIR:Ag; determined by rocket electrophoresis) and reticulo-endothelial function (measured by means of the removal kinetics of human albumin millimicrospheres) were studied in a group of patients with chronic renal failure. F VIIIR:Ag plasma levels were increased, median 304% (interquartile ranges 211-443%) compared to the controls, median 112% (interquartile ranges 100-144%); P less than 0.01. Reticulo-endothelial function was decreased, median 8.3 micrograms/min/kg body wt (interquartile ranges 6.2-10.1 micrograms/min/kg body wt) compared to the controls, median 15.0 micrograms/min/kg body wt (interquartile ranges 11.9-19.0 micrograms/min/kg body wt); P less than 0.02. A significant inverse relationship was found between plasma levels of F VIIIR:Ag and the reticulo-endothelial function rs = 0.075; P less than 0.01). As the main site of catabolism of F VIIIR:Ag is the reticulo-endothelial system, the impairment of its function appears to be a possible explanation for the elevated plasma levels of the F VIIIR:Ag found in patients with end stage renal disease.