Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles (200 microm mean diameter) was most efficient with a simple emulsion technique that dispersed 122.5 mg/g of polymer. Scanning electron micrographs showed smooth or pitted particles. Dissolution studies were correlated with microparticle morphology, indicating higher release with pitted particles when vancomycin was encapsulated in a dissolved state. The cytocompatibility of these poly(epsilon-caprolactone) microparticles was demonstrated by a direct contact cytotoxic assay. This material can be considered as an efficient drug delivery system for bone implantation.

[Medical treatment of hypertrophic myocardiopathy. Comparison of propranolol and verapamil]. / Traitement médical de la myocardiopathie hypertrophique. Comparaison entre le propranolol et le vérapamil.

It remains difficult to make a reasoned choice between betablockers and calcium antagonists in the medical treatment of hypertrophic cardiomyopathy. In order to help in making this choice, we compared the effects of 320 mg of propranolol and 480 mg of verapamil, prescribed in a random order for an average period of 2.5 months in 24 patients. In 15 patients the two therapeutic sequences were preceded and followed by a clinical examination and an exercise stress test after withdrawal of all treatment. The overall functional status correlated to oxygen consumption was unchanged by the two drugs, but patients felt better more often with verapamil. These was no significant change in maximal power developed during exercise testing although verapamil increased it by 9 p. 100 throughout with a corresponding increase in oxygen consumption. Two parameters were significantly changed by both drugs: the maximal heart rate fell from 161 +/- 22 to 122 +/- 18 with propranolol, and to 145 +/- 28 with verapamil; the oxygen pulse (equivalent to the systolic index) increased from 10.9 +/- 2.2 to 14.8 +/- 3.9 with propranolol, and to 13.7 +/- 2.4 with verapamil. There were no changes in the blood pressure profiles during exercise. Side effects were observed with both drugs; muscular weakness was the biggest problem with propranolol and sinus node dysfunction with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experimental study of the subacute toxicity of mitoxantrone and doxorubicin in rats (subcutaneous and/or intraperitoneal route)]. / Etude expérimentale de la cardiotoxicité subaiguë de la mitoxantrone et la doxorubicine chez le rat. (voie sous-cutanée et/ou intrapéritonéale).

The aims of this study were to compare experimentally the subacute cardiotoxicity of a new anthracycline, mitoxantrone (MIT) with doxorubicin (ADM), the reference anthracycline drug. Seventy nine male rats were divided into 5 groups receiving one of the drugs or a placebo by subcutaneous (SC) or intraperitoneal (IP) injection, each week for 13 weeks. The surviving rats were sacrificed at the 21st week. Group I comprised 16 rats which received 2 mg/kg AMD-IP. The mortality rate was 50% between the 14th and 18th week. Twelve of the 16 cases had a haemorrhagic ascites. The heart was normal macroscopically and on light microscopy. However, electro microscopy showed moderate myocytic degeneration. Group II comprised 16 rats which received 0.6 mg/kg MIT-IP. Morality was 100% at the 11th week. Groups III and IV comprised 32 rats; half of the animals were given 0.6 mg/kg MIT-SC and the other half 0.4 mg/kg MIT-SC. The results were identical: good clinical tolerance, normal macroscopy. Three cases of lymphocytic myocarditis and in 4 out of 8 cases very mild myocardial degeneration on electron microscopy. Group V comprised 15 rats which were given NaCl 9% SC or IP; there were no complications. These results show that mitoxantrone given IP produced major peritoneal toxicity. On the other hand, it was well tolerated when given SC and only produced mild myocardial degenerative changes.

[Comparison of the cardiotoxicity of adriamycin and aclacinomycin A in the rat. Optical and electron microscopic study]. / Comparaison de la cardiotoxicité de l'adriamycine et de l'aclacinomycine A chez le rat. Etude en microscopie optique et électronique.

Adriamycin (ADM) is a very effective antimitotic agent but its use is limited by its cardiotoxicity. New anthracycline drugs such as aclacinomycin A (ACMA) have been developed and have to be compared with ADM after chronic experimental intoxication. Three groups of randomised rats were compared: the ADM group receiving 2 mg/kg/week X 13 by intraperitoneal injection; the ACMA group receiving 4 mg/kg/week X 13 and a control group: 7 rats. The rats were autopsied at the 20th week. The heart was stopped in diastole and fixed by aortic retroinfusion of glutaraldehide for electronic microscopy (EM). In the ADM group, mean weight fell from the 4th week and mortality was 11/16 at 20 weeks. Voluminous haemorrhagic ascites was associated with peritoneal fibrosis in 12/16. Cardiac failure was observed in 4 cases but on light microscopy (LM) myofibril degeneration was constant and focal without sarcoplasmic reticulum or mitochondrial changes on EM. In the ACMA group the loss of weight occurred at 10 weeks and mortality due to toxicity was nil. There was no cardiac failure; myocytolysis was absent on LM and slight in 4/13 cases on EM with a moderate dilatation of the sarcoplasmic recticulum and presence of numerous residual bodies in the striated skeletal fibres in 5/15 cases. In this study, the ACMA had very little cardio and general toxicity in comparison with ADM. The technique of fixing the heart by retrograde infusion prevents, as far as possible, artefacts on EM affecting mainly the mitochondria.

[Aortic stenosis in adults: contribution of catheterization to the study of associated lesions. Apropos of 137 cases]. / Le rétrécissement aortique de l'adulte: apport du cathétérisme pour l'étude des lésions associées. A propos de 137 cas.

The results of cardiac catheterisation in 137 cases of pure adult aortic stenosis considered to be isolated after non-invasive investigation (clinical examination, carotid pulse tracing, echocardiogramme) are reported. The authors analyse the reliability and risks of this examination to which they attribute a triple objective; evaluation of the severity of the AS, evaluation of LV and/or mitral valve dysfunction and the assessment of the coronary circulation in patients with angina or in all patients over 54 years of age or with coronary calcifications. The aortic valve was crossed in 89,8 p. 100 of patients. Coronary angiography was attempted in 128 cases (93,4 p. 100) and was successful in 110 cases (85,9 p. 100). The investigation was complicated by one death (0,73 p. 100) and one femoral artery thrombosis, and was complete in only 74 p. 100 of cases. The results showed the aortic stenosis to be isolated in only 84 cases (61,3 p. 100). In the other 53 cases (38,7 p. 100) there was unrecognised associated pathology: mitral valve disease was diagnosed in 14 cases (12,3 p. 100); significant coronary artery disease (greater than 50 p. 100 narrowing) was observed in 34 of the 110 patients in whom coronary angiography was successful (30,9 p. 100). In the last 5 cases, catheterisation showed: two ASDs, one partial abnormal pulmonary venous drainage, one fusiform aneurysm of the aortic isthmus, one abnormal origin of the left anterior descending artery in the right coronary sinus with a pre-pulmonary trajectory. The authors discuss the value of the various methods of preoperative assessment of AS. The relative reliability of the different non-invasive techniques is compared.(ABSTRACT TRUNCATED AT 250 WORDS)

The respective roles of gallium 67 citrate scanning and diagnostic ultrasound in detecting suppurations in renal allograft recipients.

The authors report their experiments relative to the advantage of using gallium 67 scanning in the diagnosis of suppurative lesions in renal allograft recipients. Nineteen cases suggesting abscess were analyzed. In 7 cases in which abnormal isotope uptake was noted, a suppuration was detected in the area where the gallium 67 had accumulated. In 2 cases, the abnormal image corresponded to the location of a healing drained abscess, and, in 1 case of pathological uptake at the level of the graft, it was determined that the cause was chronic rejection without suppurative lesion. In 9 cases in which no abnormal focus of uptake was noted, the symptomatology suggesting abscess was eventually attributed to nonsuppurative causes (rejection, urinary fistula, etc.). It is concluded that gallium 67 scanning is a useful means of detecting suppurations in immunodepressed patients undergoing treatment with steroids which prevent the usual signs of suppuration from appearing. Generally, it can be said that diagnostic ultrasound, performed with respect to the area of abnormal gallium 67 uptake, permits optimum determination of the possibilities of an abscess existing.