Effects of different formulations of mitoxantrone (solutions, nanospheres, liposomes) on glaucoma surgery in rabbits.

Pharmacological blockade of fibroblastic proliferation after glaucoma filtration surgery by using antimitotic agents in different formulations (liposomes, nanospheres) is of great clinical interest. However, only limited comparative data are available on the effect of encapsulated drugs on intraocular pressure (IOP) after filtering surgery. Therefore we have studied the effect on IOP of liposomes, nanospheres and a solution of mitoxantrone (MTO), a well-known antimitotic, in rabbits before and after sclerectomy. MTO in solution form, as well as in a liposome formulation, improved the outcome of the surgery by reducing IOP when administered subconjunctivally just following surgery. This effect was similar to mitomycin-C application. In contrast, neither prior administration nor subconjunctival nanosphere injections induced a reduction in IOP. Liposome administration demonstrated no delayed action or promoting effect but reduced the occurrence of corneal opacity observed in groups treated with MTO in solution.

[Acute methotrexate poisoning: apropos of 16 cases reported to the Paris Poison Control Center and review of the literature]. / L'intoxication aiguë au méthotrexate: a propos de 16 cas rapportés au Centre Anti-Poisons de Paris et revue de la littérature.

16 cases of acute methotrexate (MTX) poisoning were reported to the Paris Poison Control Centre and 62 others were published between 1974 and 1995. Until 1992, MTX was mainly prescribed for neoplastic diseases. Clinical features involve acute renal failure, pancytopenia, and cutaneous or mucous injury. These cases emphasise major risk factors responsible for misuse and overdosage. Since 1992, MTX has been increasingly used in rheumatological or pulmonary diseases (rheumatoid arthritis, steroid-dependent asthma). Most of the overdosages were due to a medical misuse (in the dosage regimen or a misunderstanding of the prescription by nurse, pharmacist or patient). All patients had a bone marrow suppression. The treatment is based especially on early administration of folinic acid rescue.

Antiproliferative activity of a liposomal delivery system of mitoxantrone on rabbit subconjunctival fibroblasts in an ex-vivo model.

Wound healing is the main cause of the failure of filtering surgery in glaucoma. We developed a liposomal delivery system of mitoxantrone (MITX), an anthracyclin derivative, to allow a single adjuvant administration and to lessen ocular side-effects of the drug. In order to evaluate the antiproliferative activity of liposomal MITX, an ex vivo model consisting in the culture of subconjunctival tissue explants from rabbits pretreated with subconjunctival injections of free or liposomal MITX was used. We found that both forms of MITX decreased the growth rate as well as the explant proliferation surfaces 15 days or 1 month after a single administration of the drug in vivo. A morphometric analysis of the cells showed that the surface of the fibroblasts exposed to both forms of MITX was from 10 to 12 times as important as that of the control cells exposed to the empty liposomes and to the control buffer. A radioautographic study showed that more than 95% of the fibroblasts exposed to both forms of MITX were in the G1 phase of the cell cycle, while the control cell population was equally distributed among the different phases of the cell cycle.

[Acute toxicity of zidovudine. Analysis of the literature and number of cases at the Paris Poison Control Center]. / Toxicité aiguë de la zidovudine. Analyse de la littérature et des cas notifiés au centre Anti-Poisons de Paris.

13 cases of zidovudine overdosage have been previously published; 30 have been notified to Paris Control Poison Centre up to January 1991. This analysis shows that acute toxicity appears infrequent and mild when ingested dose is lower than 25 gr. However it appears from this series that an haematologic monitoring is needed because of the risk of myelosuppression.

[Drug-induced aseptic meningitis]. / Les méningites aseptiques d'origine médicamenteuse.

Aseptic meningitis is a very rare drug reaction involving non-steroidal antiinflammatory agents (ibuprofen and sulindac), antibiotics (cotrimoxazole, trimethoprim, ciprofloxacin) and miscellaneous drugs such as carbamazepine, human immune globulin and muromonab CD3. Meningeal symptoms occur a few hours after drug intake and resolve without sequelae within one or two days after drug withdrawal, mainly in young females with systemic lupus erythematosus or mixed connective tissue disease. Biological findings and radiological investigations are not suggestive of an infectious etiology or rheumatological/neurological disturbances. Diagnosis is simple when recurrent episodes coincide with drug ingestion.