Search

Competing Interests: Intérêts concurrents: Aucun déclaré.

Introduction: Interstitial pregnancy accounts for 3 to 11% of ectopic pregnancy; these pregnancies are the more frequently non-tubal ectopic pregnancy. Medical treatment can be used in case of unruptured interstitial pregnancy and is used more and more frequently to avoid hemorrhagic risk and risk of conversion to radical surgery when a surgical management is decided. However, a larger use of methotrexate in interstitial pregnancy and conditions of use are not clearly defined. The aim of this study is to report a series of unruptured interstitial pregnancy managed by in situ injection of methotrexate., Women and Methods: This retrospective observational study included women treated for an interstitial pregnancy between 2010 and 2013 in a teaching hospital. Medical management used was an in situ injection of methotrexate (1mg/kg) guided by vaginal sonography plus an intramuscular injection of methotrexate (1mg/kg) in the 48hours following in situ injection and 600mg of mifepristone when progesterone blood rate was more than 9ng/mL. A great decrease of serum hCG without surgery was considered a success., Results: Fourteen women had an interstitial pregnancy during the study period. Six were managed surgically in 5 cases for suspicion of uterine rupture and one for pregnancy of unknown location. Eight women had a medical management and the success rate was 100%. Mean time for decrease of serum hCG until 2 UI/L was 54.4 days [34.0-74.8]. No uterine rupture or immediate complication was reported. Five women out of 8 had a spontaneous pregnancy after management of interstitial pregnancy., Conclusion: Medical management by in situ injection of methotrexate under sonographic guidance with an intramuscular injection within the 48hours following the in situ injection and mifepristone when ectopic pregnancy was active can be proposed in first-line therapy in case of unruptured interstitial pregnancy. This treatment has a great efficiency and low rate of complications., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Methotrexate is a folic acid analog, which is a thymidylate synthetase and dihydrofolate reductase inhibitor. It is used in oncology, dermatology and rheumatology and off labelling in the treatment of ectopic pregnancies. This paper is a review of methotrexate pharmacology with focus on data concerning ectopic pregnancies., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Unlabelled: Takayasu's disease is a nonspecific aortic arteritis that affects mostly young women and sometimes children. Usual treatment consists of early and prolonged steroids. Some patients do not respond to this treatment, become steroid-dependent or suffer from side effects. We report a case in which methotrexate proved to be effective., Case Report: A 6-year-old girl presented with Takayasu's disease with elevated blood pressure of renovascular origin. Corticosteroids controlled the inflammatory syndrome but not the renal involvement and stopped the growth. Methotrexate (10 mg/m2/week) resulted in the control of the disease, the reduction of steroids and normal growth., Conclusion: In Takayasu's disease, steroids should be given as first-line therapy. In case of failure, side effects or steroid dependency, small doses of methotrexate may facilitate the disease's control and weaning from the steroids.

High dosage methotrexate is currently used in the treatment of malignancies. When used at low- or moderate doses, methotrexate has antiproliferative and antiinflammatory effects and is a useful drug in skin diseases. The aim of this review is to describe pharmacology, indications, adverse effects and practical use in Dermatology. Pharmacodynamics of methotrexate is especially related to antifolic activity. Methotrexate is officially approved in the treatment of severe psoriasis, but many other proliferative or inflammatory diseases with cutaneous manifestations may benefit from this drug, usually in association with corticosteroids. The use of methotrexate needs some precautions and a precise follow-up to minimise the risk of severe adverse effects. However, efficacy of methotrexate was reported in open and retrospective small size studies. Prospective and comparative trials are required to confirm the indications, advantages and tolerance of methotrexate in dermatology.

Methotrexate is now being used in the treatment of unruptured ectopic pregnancy. Experimental studies have shown that methotrexate inhibits the proliferation of normal trophoblast cells and that it has nos deleterious effect on tubal epithelium and no long-term teratogenic effect. Its pharmacokinetics is about the same when it is administered systemically or by intratubal injection. The clinical results obtained are independent of the mode of administration, with an 80 percent success rate. Thus, in the treatment of unruptured ectopic pregnancy methotrexate is a good alternative to laparoscopic surgery. The fertility of women treated with this drug seems to be preserved, but the published data are still insufficient and fragmentary.

Successful treatment of four, non ruptured, cases of interstitial pregnancy are reported. Treatment consisted of in situ injection of methotrexate during coelioscopy. Dosage was 1.5 mg methotrexate per kilogram body weight. Negative plasma beta hCG levels were obtained 9 to 22 days after conservative medical treatment. No clinical or biochemical side effects were observed. Of two patients had no radiologically demonstrable cornual abnormality on the hysterosalpingographies effected at the 3 months evaluation after ascertained interstitial pregnancy, one have normal pregnancy. Two further patients had normal uneventful pregnancies 12 to 15 months later. Treatment of interstitial pregnancy by way of one in situ injection of methotrexate seems to be the currently preferred alternative to classical surgery.

Methotrexate (MTX) has been proved to be effective in rheumatoid arthritis (RA). The mechanism of action of MTX in this disease remains unelucidated but may involve inhibition of the enzyme 5-lipoxygenase. Arachidonic acid metabolites were studied in eight patients with active RA immediately prior to and 24 hours after the first intramuscular injection of 10 mg MTX. None of the patients were taking corticosteroids. Nonsteroidal antiinflammatory drugs were withdrawn four days before the study. Reverse phase high-performance liquid chromatography was used to quantitate metabolites produced by 5-lipoxygenase (5-LO) and 12-LO in plasma (full spectrum of blood cells) and purified neutrophils (PN) after stimulation with calcium ionophore A 21387 (50 microM for 30 minutes and 5 microM for 5 minutes, respectively). LTB4 production by PNs was significantly decreased (-32%, p < 0.01) 24 hours after MTX administration. A moderate (-17%), nonsignificant (NS) fall in LTB4 omega-oxidation products (wP) was seen. Production of 5-HETE was also slightly decreased (-15%, NS). Findings in plasma were comparable, with a significant decrease in total LTB4 (-29.8%, p < 0.01) and moderate falls in wP (-18.8%, NS) and in 5-HETE production (-17%, NS). Production of 12-HETE was unchanged. These findings suggest that MTX in a single dose is responsible for a decrease in the synthesis of LTB4 and 5-LO products in neutrophils and other blood cells in RA patients but does not affect 12-LO activity.

Methotrexate, at doses inhibiting cell growth without any lethal effect, alters oxygen consumption in L 1210 cells as soon as 3 hrs. after culture. After a 24 hrs. treatment with methotrexate, there is a close relationship between cellular oxygen uptake and growth inhibition. These two effects are reversible. With mitochondria from treated cells, an inhibition of respiration is observed in the presence of glutamate-malate. No effect occurs with succinate. These results in vitro are compatible with concentrations used in patients.

Sodium butyrate at a concentration of 1 x 10(-3) M or lower seems to decrease the rate of cellular proliferation through the cell cycle in G 1 phase. This effect makes them more sensitive to the cytotoxic action of moderate doses of methotrexate.

Methotrexate, at non lethal doses, alters the glycolysis of leukaemic L 1210 cells. Glucose uptake and lactate excretion are increased but lactate/glucose ratio remains constant. The activity of glycolytic enzymes in the cytoplasm is increased and the level of intracellular ATP is greatly enhanced.

A diminution of the mitotic index, proportionnal to the square of the dose of methotrexate, was observed in lymphocyte cultures. Six trisomy 21 patients were twice as sensitive as six controls. This highly significant result confirms the hypothesis of a disturbance of monocarbons' metabolism in trisomy 21.

The authors studied distraction osteogenesis in an animal subjected to prolonged anti-mitotic chemotherapy (Methotrexate and Doxorubicin). This chemotherapy decreased osteogenesis (essentially at the expense of external regeneration) though without inhibiting it totally. Distraction bone consolidation is thus possible in the animal, permitting reconstruction of limb segments by mobilization of an axial fragment in accordance with the Ilizarov technique.

Antigenic competition cannot be obtained in congenital athymic Nude mice, whatever the dose of inhibitor Ag used and the free interval between inhibitory Ag injections and the Ag test. On the other hand, competition is normal and even increased, in thymectomised, adult Swiss mice, used 10 to 30 days after thymectomy. In normal mice, the inhibitory mechanism induced by a first thymodependent antigen, may also occur with regard to certain thymo-independent antigens and thus act on the B cells. The antigens may also serve as inhibitory antigens for thymodependent antigens if the free interval between the two injections is small. Injection of hydrocortisone (25 mg/kg) or ALS a short time before the inhibitory antigens, suppresses competition. On the other hand, methotrexate is without effect. Thus the inhibitory TD mechanism does not require mitoses (methotrexate) and depends on corticosensitive T cells which are, no doubt, recirculated (Anti-lymphocyte serum) with a life span greater than 30 days (adult thymectomy). The previous results were obtained when two antigens were administered by intraperitoneal route and the PF cells sought in the spleen. The same experiment was carried out, injecting two antigens subcutaneously, in the same limb, and counting the PF cells in the appropriate lymph node; it shows the adjuvant effect exerted by the first antigen on the response with regard to the second antigen. On the other hand, inhibition is produced if the first antigen is injected intraperitoneally or into another limb. One may thus distinguish an inhibitory effect or an adjuvant effect depending on the experimental conditions. The inhibitory effect seems to be related to the T cells with an immunosuppressive function.

After confirming the increase of the fragility of the site Xq27 by methotrexate and its decrease by 5-formyltetrahydrofolate, it is observed that L-serine, 5-amino-levulinate and L-4-hydroxy-proline at millimolar concentrations, reduce considerably the frequency of the anomaly in lymphocyte cultures. The possible relationships between this chromosomal marker, the one carbon cycle,and mental deficiency of the patients, are discussed.

The perfusion of cytotoxic drugs in the treatment of inoperable tumours of liver is used even in children. The experiment described here was planned to study the effect of three cytotoxic drugs (5. Fluorouracil, Méthotrexate and S.P.I.) on the liver of healthy baboons. The drugs were introduced by perfusion through the hepatic artery. Liver biopsies were performed at the end of the treatment and 15 and 60 days later. In order to avoid acute toxic effects, low doses of the drugs must be given during the first five days. The therapeutic dose can then be increased and maintained for variable periods. Of the three products tested, the toxicity increases in the following order: S.P.I., 5 F U. and Methotrexate.