Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vesse...Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vessels, heart, lungs, nervous system, and other organs. Methotrexate (MTX) is the anchor drug that treats RA. As renal and liver abnormalities are more common during disease conditions as well as during the treatment period, we tried to find out if there is any impact of MTX in these organs during the treatment of RA patients. Once the disease complications are developed, it is quite difficult to reverse the disease, and treatment in this situation is not very effective. Consequently, patients suffer a lot. So, early evaluation of renal and liver function is essential for the treatment of RA patients and it might also help prevent different complications which are usually very frequently observed. This was a cross-sectional study. A total of 150 RA patients treated with MTX were evaluated for the study where female and male respondents were 115 and 35 respectively. In this study, we found that 82% of RA patients had creatinine levels ≤ 1.1 mg/dL although the normal range of serum creatinine is below 1.4 mg/dL. Usually, a 15% increase in Serum creatinine level from the baseline is considered renal impairment. We found 4% of such cases. Moreover, 2% of RA patients had creatinine levels above the normal range of 1.4 mg/dL and those patients were hypertensive as well. So, a total (4 + 2 = 6)% had renal impairments. Among them, 5% had diabetes mellitus. On the other hand, the ultrasonogram (USG) of RA patients with kidney disease showed signs of renal parenchymal disease and 3% of RA patients having renal problems whose serum creatinine level was within the normal range showed signs of chronic kidney disease (CKD). On the other hand, 2% of RA patients showed signs of hepatic parenchymal disease. In this study, 69% of RA patients had ALT levels ≤ 50 mg/dL, 23% had 50 - 100 mg/dL, and 5% had 101 - 150 mg/dL. The remaining 3% of RA patients had ALT levels above 150 mg/dL. All those patients with ALT levels above 100 mg/dL used Nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly. Different parameters of liver and renal function should be monitored strongly in RA patients treated with MTX and NSAIDs. MTX should not be given for a prolonged period without monitoring renal and liver function. As MTX, Diabetes Mellitus, Hypertension, etc., may cause renal complications, we could not concretely conclude which one is the actual causative agent.展开更多
Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to eva...Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.展开更多
Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence ...Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.展开更多
Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than ...Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.展开更多
AIM:To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine(NAC),amifostine(AMF)and ascorbic acid(ASC)in methotrexate(MTX)-induced hepatotoxicity.METHODS:An MTX-...AIM:To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine(NAC),amifostine(AMF)and ascorbic acid(ASC)in methotrexate(MTX)-induced hepatotoxicity.METHODS:An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of20 mg/kg MTX.Eleven of the rats were left untreated(Model group;n=11),and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX+NAC group;n=11),50 mg/kg per single dose AMF(MTX+AMF group;n=11),or 10 mg/kg per day ASC(MTX+ASC group;n=11).Eleven rats that received no MTX and no treatments served as the negative control group.Structural and functional changes related to MTX-and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde(MDA),superoxide dismutase(SOD),catalase,glutathione(GSH)and xanthine oxidase activities and of serum levels of aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and total bilirubin.RESULTS:Exposure to MTX caused structural and functional hepatotoxicity,as evidenced by significantly worse histopathological scores[median(range)injury score:control group:1(0-3)vs 7(6-9),P=0.001]and significantly higher MDA activity[409(352-466)nmol/g vs 455.5(419-516)nmol/g,P<0.05].The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents,but only the reduction in hepatotoxicity scores reached statistical significance[4(3-6)for NAC,4.5(3-5)for AMF and 6(5-6)for ASC;P=0.001,P=0.001 and P<0.005vs model group respectively].Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues[control group:3.02(2.85-3.43)μmol/g and 71.78(61.88-97.81)U/g vs model group:2.52(2.07-3.34)μmol/g and 61.46(58.27-67.75)U/g,P<0.05];however,only the NAC treatment provided significant increases in these antioxidant enzyme activities[3.22(2.54-3.62)μmol/g and 69.22(61.13-100.88)U/g,P<0.05 and P<0.01vs model group respectively].CONCLUSION:MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress,and cytoprotective agents(NAC>AMF>ASC)may alleviate MTX hepatotoxicity.展开更多
Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bo...Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.展开更多
AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Pati...AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.展开更多
Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing c...Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.展开更多
Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(...Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.展开更多
We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Departme...We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.展开更多
AIM:To evaluate the effectiveness and corticosteroidsparing capabilities of methotrexate(MTX)in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients.METHODS:A retrospective chart review of a...AIM:To evaluate the effectiveness and corticosteroidsparing capabilities of methotrexate(MTX)in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients.METHODS:A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted.All patients received 10 to 15 mg/wk MTX orally,and corticosteroids(10 to 40 mg/d prednisolone or equivalent methylprednisolone)with slow tapering.Topical corticosteroid eye drops(1%prednisolone actate,0.1%dexmathosone or 0.1%fluoromethalone)were applied to control comorbid anterior uveitis at presentation or during follow up.The main outcomes were inflammation control and corticosteroid-sparing success,and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity(BCVA).RESULTS:Thirty-two eyes(22 patients)were included.The proportion of patients who achieved corticosteroidsparing success was 50.0%at 3mo and 77.3%at 12mo[8(36.4%)patients discontinued corticosteroid].The proportion of eyes that achieved inflammation control was 59.4%at 3mo and 78.1%at 12mo.The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo(P<0.01).BCVA maintained unchanged or improved in 29(90.6%)of all affected eyes.One patient discontinued MTX treatment because of an abnormal liver function test,and no other serious adverse effects were observed.CONCLUSION:According to this pilot study,low dose MTX appear to be a well-tolerated and effective treatment for chronic non-necrotizing anterior scleritis patients in the Chinese population.展开更多
BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that ofte...BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.展开更多
Introduction: Ectopic pregnancy is dreadful and can lead to the death of the patient if it is ignored. Diagnosed early, it offers the possibility of medical treatment with methotrexate. Objective: To describe the prog...Introduction: Ectopic pregnancy is dreadful and can lead to the death of the patient if it is ignored. Diagnosed early, it offers the possibility of medical treatment with methotrexate. Objective: To describe the prognosis of ectopic pregnancies treated methotrexate. Patients and Methods: Retrospective study of the management of ectopic pregnancy by Methotrexate at Senlis hospital from June 2020 to May 2021 were included in the study, patients with a Fernandez score of less than 13, and having received Methotrexate as first-line treatment. Data were collected using gynecological emergency admission registers, and telephone interviews. Results: 35 cases were identified. The average age of the patients was 32 years old. Forty-nine percent were smokers. The mean gestational age was 5 weeks + 2 days. The diagnosis was made in all of our patients with the combination of the kinetics of ß-hcg and vaginal ultrasound. The size of adnexal mass was less than 4 cm with an average size of 20 mm. The average value of ß-hcg was 1405 IU/L. All patients had received a single dose of methotrexate 1 mg/kg intramuscularly. A second dose was administered to 17.1% of patients for stagnation or re-ascension of the ß-hcg level. The success rate was 91.4%. Thirty percent were obtained spontaneous intra uterine pregnancy, the first year following methotrexate treatment. Conclusion: The success rate of medical treatment for ectopic pregnancy is high in terms of meeting the eligibility criteria for treatment. The subsequent prognosis of fertility is generally preserved.展开更多
Interstitial ectopic pregnancies are very rare, however, they are extremely dangerous. Treatment consists of either surgical or medical management. This patient presented with no prior pregnancies, an inappropriately ...Interstitial ectopic pregnancies are very rare, however, they are extremely dangerous. Treatment consists of either surgical or medical management. This patient presented with no prior pregnancies, an inappropriately rising b-hCG, and eventually had ultrasound findings consistent with interstitial ectopic pregnancy. She was seen through the Emergency Department and had no insurance. She strongly desired to avoid surgery, and was successfully given a multi-dose regimen of methotrexate. Contraindication to methotrexate management includes an inability to follow-up, so a close therapeutic alliance was maintained to enable safe resolution of this case. She has since successfully carried an uncomplicated intrauterine pregnancy to term.展开更多
Although high-dose methotrexate(HD-MTX)is the most effective drug against primary CNS lymphomas(PCNSL),outcome-de-termining variables related to its administration schedule have not been defined.The impact on toxicity...Although high-dose methotrexate(HD-MTX)is the most effective drug against primary CNS lymphomas(PCNSL),outcome-de-termining variables related to its administration schedule have not been defined.The impact on toxicity and outcome of the area under thecurve(AUC(MTX)),dose intensity(DI(MTX))and infusion rate(IR(MTX))of MTX and plsamatic creatinine clearance(CL(crea))was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-basedcombinations.Anticon-vulsants were administered in 31 pts(69%).Age>60 years,anticonvulsant therapy,slow IR(MTX)(</=800 mgm(-2)h(-1)),and reduced DI(MTX)(</=1000 mgm(-2)wk(-1))were significantly correlated with low AUC(MTX)values.Seven pa-展开更多
<strong>Introduction:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Cervico-isthmic pregnancy is rare, and serious bec...<strong>Introduction:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Cervico-isthmic pregnancy is rare, and serious because of its hemorrhagic complication. Its management varies according to the teams. </span><b><span style="font-family:Verdana;">Observation:</span></b><span style="font-family:Verdana;"> We report a case of cervico-isthmic pregnancy on a cesarean scar. This is a 35-year</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">old, G2P2, who consulted for bleeding from the 1st trimester of pregnancy. </span><a name="_Hlk80358912"></a><span style="font-family:Verdana;">The clinical examination found a minimal uterine bleeding. The diagnosis was made by a vaginal ultrasound which found a cervico-isthmic implantation of the pregnancy on the caesarean scar. A protocol of Mifepristone and Misoprostol followed by administration of a single dose of 1 mg/kg of Methotrexate was performed. Cure was obtained 1 month after treatment by negativation of plasma HCG. No bleeding complications were noted. A follow-up ultrasound performed 2 months later showed a uterine vacuity and the presence of an isthmocoele. It was in fact a pregnancy that had implanted in the isthmocoele. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Cervico-isthmic pregnancy is rare. His treatment is not codified. Drug management was successful</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span>展开更多
Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Th...Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.展开更多
The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats.A simple and efficient hig...The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats.A simple and efficient high performance liquid chromatography coupled with mass spectrometry(HPLC-MS)method was developed to determine methotrexate in rat plasma.Methotrexate and syringic acid(internal standard)were extracted from rat plasma samples by protein precipitation with acetonitrile.The analysis was performed on a CAPCELL PAK C18column(150 mm×4.6 mm,5μm)with acetonitrile and 5 mmol/l ammonium acetate aqueous(10:90,v/v).The linear range was 5.0×10-2to 100.0μg/ml for methotrexate.Other parameters were all within the acceptance criteria.The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups(with and without the pretreatment of piperazine ferulate).Compared with the methotrexate treated alone group,the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT(0-t),MRT(0-∞) and T1/2.Results suggested that methotrexate can be rapidly eliminated,cleared or metabolized in rat blood,which might be related to the pretreatment of piperazine ferulate.The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.展开更多
BACKGROUND Immunosuppression is effective in treating a number of diseases,but adverse effects such as bone marrow suppression,infection,and oncogenesis are of concern.Methotrexate is a key immunosuppressant used to t...BACKGROUND Immunosuppression is effective in treating a number of diseases,but adverse effects such as bone marrow suppression,infection,and oncogenesis are of concern.Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis.Although it is effective for many patients,various side effects have been reported,one of the most serious being methotrexate-related lymphoproliferative disorder.While this may occur in various organs,liver involvement is rare.Information on these liver lesions,including clinical characteristics,course,and imaging studies,has not been summarized to date.CASE SUMMARY We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain.She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate.Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3,CD4,CD8,and CD79a but negative for CD20 and CD56.Staining for Epstein-Barr virus-encoded RNA was negative.And based on these findings,the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders.A timedependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses.CONCLUSION The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.展开更多
文摘Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vessels, heart, lungs, nervous system, and other organs. Methotrexate (MTX) is the anchor drug that treats RA. As renal and liver abnormalities are more common during disease conditions as well as during the treatment period, we tried to find out if there is any impact of MTX in these organs during the treatment of RA patients. Once the disease complications are developed, it is quite difficult to reverse the disease, and treatment in this situation is not very effective. Consequently, patients suffer a lot. So, early evaluation of renal and liver function is essential for the treatment of RA patients and it might also help prevent different complications which are usually very frequently observed. This was a cross-sectional study. A total of 150 RA patients treated with MTX were evaluated for the study where female and male respondents were 115 and 35 respectively. In this study, we found that 82% of RA patients had creatinine levels ≤ 1.1 mg/dL although the normal range of serum creatinine is below 1.4 mg/dL. Usually, a 15% increase in Serum creatinine level from the baseline is considered renal impairment. We found 4% of such cases. Moreover, 2% of RA patients had creatinine levels above the normal range of 1.4 mg/dL and those patients were hypertensive as well. So, a total (4 + 2 = 6)% had renal impairments. Among them, 5% had diabetes mellitus. On the other hand, the ultrasonogram (USG) of RA patients with kidney disease showed signs of renal parenchymal disease and 3% of RA patients having renal problems whose serum creatinine level was within the normal range showed signs of chronic kidney disease (CKD). On the other hand, 2% of RA patients showed signs of hepatic parenchymal disease. In this study, 69% of RA patients had ALT levels ≤ 50 mg/dL, 23% had 50 - 100 mg/dL, and 5% had 101 - 150 mg/dL. The remaining 3% of RA patients had ALT levels above 150 mg/dL. All those patients with ALT levels above 100 mg/dL used Nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly. Different parameters of liver and renal function should be monitored strongly in RA patients treated with MTX and NSAIDs. MTX should not be given for a prolonged period without monitoring renal and liver function. As MTX, Diabetes Mellitus, Hypertension, etc., may cause renal complications, we could not concretely conclude which one is the actual causative agent.
基金supported by the National Natural Science Foundation of China(No.81700147 and No.82070172).
文摘Objective:Methotrexate(MTX)can be safely administered to most patients but may cause severe toxicity in others.This study aimed to summarize the characteristics of high-dose methotrexate(HD-MTX)chemotherapy and to evaluate whether the modified dose-adjustment program was able to improve the maintenance of sufficient MTX exposure levels while minimizing toxicities.Methods:We evaluated 1172 cycles of high-dose MTX chemotherapy from 294 patients who were treated according to the CCCG-ALL-2015 protocol(clinical trial number:ChiCTR-IPR-14005706)and analyzed the data of actual MTX dosage,MTX concentration,toxicity,and prognosis.We compared data between the dose-adjustment Program 1(fixed 20%reduction in dose)and the dose-adjustment Program 2(dose-individualization based on reassessment of the creatine clearance rate and the MTX concentration-monitoring point at 16 h),which were applied if the MTX clearance was delayed in the previous cycle.Results:The patients who used Program 2 had higher actual MTX infusion doses and infusion rates and were able to better maintain the MTX concentration at 44 h at the established target value than those on Program 1(P<0.001).No significant differences in toxicities were found between these two programs except that abnormal serum potassium levels and prolonged myelosuppression in intermediate-risk/high-risk patients were more frequently observed in patients using Program 2(P<0.001).No significant correlations were observed between the MTX dose,dose-adjustment programs,or MTX concentrations and relapse-free survival.Conclusion:Adjusting the MTX dose using Program 2 is more efficient for maintaining sufficient MTX exposure without significantly increasing the toxicity.
基金support of the Vice-Chancellor for Research,Shiraz University of Medical Sciences,Iran(project No.97-01-36-18308)
文摘Methotrexate(MTX)is a folate antagonist drug used for several diseases,such as cancers,various malignancies,rheumatoid arthritis(RA)and inflammatory bowel disease.Due to its structural features,including the presence of two carboxylic acid groups and its low native fluorescence,there are some challenges to develop analytical methods for its determination.MTX is metabolized to 7-hydroxymethotrexate(7-OH-MTX),2,4-diamino-N10-methylpteroic acid(DAMPA),and the active MTX polyglutamates(MTXPGs)in the liver,intestine,and red blood cells(RBCs),respectively.Additionally,the drug has a narrow therapeutic range;hence,its therapeutic drug monitoring(TDM)is necessary to regulate the pharmacokinetics of the drug and to decrease the risk of toxicity.Due to environmental toxicity of MTX;its sensitive,fast and low cost determination in workplace environments is of great interest.A large number of methodologies including high performance liquid chromatography equipped with UVevisible,fluorescence,or electrochemical detection,liquid chromatography-mass spectroscopy,capillary electrophoresis,UVevisible spectrophotometry,and electrochemical methods have been developed for the quantitation of MTX and its metabolites in pharmaceutical,biological,and environmental samples.This paper will attempt to review several published methodologies and the instrumental conditions,which have been applied to measure MTX and its metabolites within the last decade.
文摘Methotrexate is the first line drug treatment for anumber of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.
文摘AIM:To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine(NAC),amifostine(AMF)and ascorbic acid(ASC)in methotrexate(MTX)-induced hepatotoxicity.METHODS:An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of20 mg/kg MTX.Eleven of the rats were left untreated(Model group;n=11),and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX+NAC group;n=11),50 mg/kg per single dose AMF(MTX+AMF group;n=11),or 10 mg/kg per day ASC(MTX+ASC group;n=11).Eleven rats that received no MTX and no treatments served as the negative control group.Structural and functional changes related to MTX-and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde(MDA),superoxide dismutase(SOD),catalase,glutathione(GSH)and xanthine oxidase activities and of serum levels of aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and total bilirubin.RESULTS:Exposure to MTX caused structural and functional hepatotoxicity,as evidenced by significantly worse histopathological scores[median(range)injury score:control group:1(0-3)vs 7(6-9),P=0.001]and significantly higher MDA activity[409(352-466)nmol/g vs 455.5(419-516)nmol/g,P<0.05].The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents,but only the reduction in hepatotoxicity scores reached statistical significance[4(3-6)for NAC,4.5(3-5)for AMF and 6(5-6)for ASC;P=0.001,P=0.001 and P<0.005vs model group respectively].Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues[control group:3.02(2.85-3.43)μmol/g and 71.78(61.88-97.81)U/g vs model group:2.52(2.07-3.34)μmol/g and 61.46(58.27-67.75)U/g,P<0.05];however,only the NAC treatment provided significant increases in these antioxidant enzyme activities[3.22(2.54-3.62)μmol/g and 69.22(61.13-100.88)U/g,P<0.05 and P<0.01vs model group respectively].CONCLUSION:MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress,and cytoprotective agents(NAC>AMF>ASC)may alleviate MTX hepatotoxicity.
文摘Methotrexate has been used an immunomodulator in many autoimmune diseases,including inflammatory bowel disease. However,many physicians are unfamiliar or uncomfortable with its use in the management of inflammatory bowel disease. We summarize the data for use of methotrexate in common clinical scenarios:(1) steroid dependant Crohn's disease(CD);(2) maintenance of remission in steroid free CD;(3) azathioprine failures in CD;(4) in combination therapy with Anti-TNF agents in CD;(5) decreasing antibody formation to Anti-TNF therapy in CD;(6) management of fistulizing disease in CD; and(7) as well as induction and maintenance of remission in ulcerative colitis. An easy to use algorithm is provided for the busy clinician to access and safely prescribe methotrexate for their inflammatory bowel disease patients.
文摘AIM: To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology. METHODS: Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2. RESULTS: There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 gradeⅠ (MCD 2885 mg), 23 grade Ⅱ (MCD 1800 mg) and 7 grade Ⅲ (MCD 1500 mg). There was no grade Ⅳ or cirrhosis. The prevalence of liver fibrosis (grade Ⅲ) was 12%. Of the factors assessed, diabetes (P=0.001) and hypertension (P=0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n=15) were stable, 34.6% (n=9) had progression and 7.7% (n=2) had regression of histological grades. On univariate analysis, nonChinese ethnicity (P=0.031), diabetes (P=0.018), and hyperlipidemia (P=0.011) were predictive of progression of grades, but these were not significant on multivariate analysis. CONCLUSION: Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.
基金the financial support of research grants from the Hong Kong Polytechnic University(Q67H)and Higher Education Commission(HEC),Pakistan for the financial support during IRSIP。
文摘Methotrexate(MTX)is one of the most consumed anti-cancer drugs in the pharmaceutical market around the world.The widespread occurrence of MTX in aquatic environment through hospital effluent has attracted increasing concern due to its potential to induce water pollution.In the present study,the degradation of MTX in aqueous medium was investigated by UV-activated peroxymonosulfate(PMS).A significant improvement in degradation rate by increasing UV intensity and PMS concentration while the decrease in degradation efficiency with the increase of solution p H and initial concentration of MTX was observed.The proposed UV/PMS process could achieve more than 90%MTX degradation in 30 min with a good mineralization degree(65%).A pseudofirst order kinetic model was employed and successfully predicted the degradation of MTX.The effect of other operational parameters such as the initial concentration of the targeted compound,dosage of oxidant(PMS),solution p H and UV intensity on the degradation rate were investigated.At the last,the main transform intermediates were identified using LC–MS and possible degradation pathways were proposed.The results show that UV/PMS can be used as an efficient technology to treat pharmaceuticals such as methotrexate containing water and wastewater.
文摘Objective: To compare the degree of ameliorative effects of Melatonin(MEL), Ursodeoxycholic acid(UDCA) and Balanites aegyptiaca(BA) against hepatotoxicity induced by MTX for one month. Methods: Eighty adult male rats(Sprague Dawely) weighing(190±10g), were randomly divided into eight equal groups: Control, MTX, MEL, BA, UDCA, MTX+MEL, MTX+BA, MTX+UDCA. Liver function biomarker enzymes, liver tissue oxidative stress parameters, together with total antioxidant capacity and tumor necrosis factor(TNF-α) were determined. Histopathological and immunohistochemistry examinations for TNF-α were also done. Results: MTX showed significant increase in alanine transaminase(ALT), aspartate transaminase(AST), alkaline phosphatase(ALP), gamma glutamyl transferase(GGT), total and direct bilirubin, as well as TNF-α levels, oxidized glutathione(GSSG), malodialdehyde(MDA) and nitric oxide(NO). whereas, total protein, albumin, total antioxidant capacity, reduced glutathione(GSH), glutathione peroxidase(GPx), glutathione reductase(GR), glutathione S-transferase(GST), superoxide dismutase(SOD) and catalase(CAT) levels were significantly decreased in MTX treated group. These alterations were improved by MEL and BA treatment, whereas no improvement was noticed in UDCA treatment. Conclusions: BA may be as promising as MEL in the hepatoprotection against MTX toxicity through their antioxidant and radical scavenging activities. In addition, it is not recommended to co-administer UDCA with MTX as it enhanced inflammation and damage to the liver.
文摘We report the case of a cervical pregnancy successfully treated with intramuscular injection of methotrexate(MTX) and intramniotic administration of potassium chloride. A 41-year-old woman was admitted to our Department with the suspicion of ectopic pregnancy. Transvaginal ultrasound revealed empty endometrialcavity, gestational sac within the cervical canal and embryonic echo measuring crown rump length 1.5 mm. Serum beta human chorionic gonadotropine(β-HCG) was measured 28590 IU/L. No cardiac activity was detected. The diagnosis of a cervical pregnancy was made. Patient was treated with intramuscular administration of methotrexate(50 mg/m2) in combination with ultrasoundguided intramniotic injection of KCl(2 meq/mL). Gradual decrease of β-HCG levels as well as ultrasound observation of collapsed gestational sac was observed. No curettage was necessitated. Patient was discharged on day 10 th and was set in follow-up on a weekly basis. β-HCG values were measured < 10 IU/L on 56 th day after MTX administration. Intramuscular administration of MTX may be effective in treatment of cervical pregnancy without additional interventional measures.
基金Supported by The Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2018PT32029)。
文摘AIM:To evaluate the effectiveness and corticosteroidsparing capabilities of methotrexate(MTX)in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients.METHODS:A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted.All patients received 10 to 15 mg/wk MTX orally,and corticosteroids(10 to 40 mg/d prednisolone or equivalent methylprednisolone)with slow tapering.Topical corticosteroid eye drops(1%prednisolone actate,0.1%dexmathosone or 0.1%fluoromethalone)were applied to control comorbid anterior uveitis at presentation or during follow up.The main outcomes were inflammation control and corticosteroid-sparing success,and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity(BCVA).RESULTS:Thirty-two eyes(22 patients)were included.The proportion of patients who achieved corticosteroidsparing success was 50.0%at 3mo and 77.3%at 12mo[8(36.4%)patients discontinued corticosteroid].The proportion of eyes that achieved inflammation control was 59.4%at 3mo and 78.1%at 12mo.The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo(P<0.01).BCVA maintained unchanged or improved in 29(90.6%)of all affected eyes.One patient discontinued MTX treatment because of an abnormal liver function test,and no other serious adverse effects were observed.CONCLUSION:According to this pilot study,low dose MTX appear to be a well-tolerated and effective treatment for chronic non-necrotizing anterior scleritis patients in the Chinese population.
基金Supported by Special Research Project of Capital Health Development 2016,No.2020-2-2048.
文摘BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P<0.001)were correlated with survival.Multivariate analysis showed that KPS>60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.
文摘Introduction: Ectopic pregnancy is dreadful and can lead to the death of the patient if it is ignored. Diagnosed early, it offers the possibility of medical treatment with methotrexate. Objective: To describe the prognosis of ectopic pregnancies treated methotrexate. Patients and Methods: Retrospective study of the management of ectopic pregnancy by Methotrexate at Senlis hospital from June 2020 to May 2021 were included in the study, patients with a Fernandez score of less than 13, and having received Methotrexate as first-line treatment. Data were collected using gynecological emergency admission registers, and telephone interviews. Results: 35 cases were identified. The average age of the patients was 32 years old. Forty-nine percent were smokers. The mean gestational age was 5 weeks + 2 days. The diagnosis was made in all of our patients with the combination of the kinetics of ß-hcg and vaginal ultrasound. The size of adnexal mass was less than 4 cm with an average size of 20 mm. The average value of ß-hcg was 1405 IU/L. All patients had received a single dose of methotrexate 1 mg/kg intramuscularly. A second dose was administered to 17.1% of patients for stagnation or re-ascension of the ß-hcg level. The success rate was 91.4%. Thirty percent were obtained spontaneous intra uterine pregnancy, the first year following methotrexate treatment. Conclusion: The success rate of medical treatment for ectopic pregnancy is high in terms of meeting the eligibility criteria for treatment. The subsequent prognosis of fertility is generally preserved.
文摘Interstitial ectopic pregnancies are very rare, however, they are extremely dangerous. Treatment consists of either surgical or medical management. This patient presented with no prior pregnancies, an inappropriately rising b-hCG, and eventually had ultrasound findings consistent with interstitial ectopic pregnancy. She was seen through the Emergency Department and had no insurance. She strongly desired to avoid surgery, and was successfully given a multi-dose regimen of methotrexate. Contraindication to methotrexate management includes an inability to follow-up, so a close therapeutic alliance was maintained to enable safe resolution of this case. She has since successfully carried an uncomplicated intrauterine pregnancy to term.
文摘Although high-dose methotrexate(HD-MTX)is the most effective drug against primary CNS lymphomas(PCNSL),outcome-de-termining variables related to its administration schedule have not been defined.The impact on toxicity and outcome of the area under thecurve(AUC(MTX)),dose intensity(DI(MTX))and infusion rate(IR(MTX))of MTX and plsamatic creatinine clearance(CL(crea))was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-basedcombinations.Anticon-vulsants were administered in 31 pts(69%).Age>60 years,anticonvulsant therapy,slow IR(MTX)(</=800 mgm(-2)h(-1)),and reduced DI(MTX)(</=1000 mgm(-2)wk(-1))were significantly correlated with low AUC(MTX)values.Seven pa-
文摘<strong>Introduction:</strong><span><span><span style="font-family:""><span style="font-family:Verdana;"> Cervico-isthmic pregnancy is rare, and serious because of its hemorrhagic complication. Its management varies according to the teams. </span><b><span style="font-family:Verdana;">Observation:</span></b><span style="font-family:Verdana;"> We report a case of cervico-isthmic pregnancy on a cesarean scar. This is a 35-year</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">-</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">old, G2P2, who consulted for bleeding from the 1st trimester of pregnancy. </span><a name="_Hlk80358912"></a><span style="font-family:Verdana;">The clinical examination found a minimal uterine bleeding. The diagnosis was made by a vaginal ultrasound which found a cervico-isthmic implantation of the pregnancy on the caesarean scar. A protocol of Mifepristone and Misoprostol followed by administration of a single dose of 1 mg/kg of Methotrexate was performed. Cure was obtained 1 month after treatment by negativation of plasma HCG. No bleeding complications were noted. A follow-up ultrasound performed 2 months later showed a uterine vacuity and the presence of an isthmocoele. It was in fact a pregnancy that had implanted in the isthmocoele. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Cervico-isthmic pregnancy is rare. His treatment is not codified. Drug management was successful</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">.</span></span></span>
文摘Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.
文摘The present study was designed to investigate the influence of the pretreatment of piperazine ferulate on pharmacokinetic parameters of methotrexate in methotrexate-induced renal injury rats.A simple and efficient high performance liquid chromatography coupled with mass spectrometry(HPLC-MS)method was developed to determine methotrexate in rat plasma.Methotrexate and syringic acid(internal standard)were extracted from rat plasma samples by protein precipitation with acetonitrile.The analysis was performed on a CAPCELL PAK C18column(150 mm×4.6 mm,5μm)with acetonitrile and 5 mmol/l ammonium acetate aqueous(10:90,v/v).The linear range was 5.0×10-2to 100.0μg/ml for methotrexate.Other parameters were all within the acceptance criteria.The validated method was successfully applied the pharmacokinetic study of methotrexate between two methotrexate treated groups(with and without the pretreatment of piperazine ferulate).Compared with the methotrexate treated alone group,the pharmacokinetic parameters in the methotrexate with the pretreatment of piperazine ferulate group showed significantly lower MRT(0-t),MRT(0-∞) and T1/2.Results suggested that methotrexate can be rapidly eliminated,cleared or metabolized in rat blood,which might be related to the pretreatment of piperazine ferulate.The method provided deeper insights into rational clinical use of methotrexate with the pretreatment of piperazine ferulate on cancer patients with renal dysfunction.
文摘BACKGROUND Immunosuppression is effective in treating a number of diseases,but adverse effects such as bone marrow suppression,infection,and oncogenesis are of concern.Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis.Although it is effective for many patients,various side effects have been reported,one of the most serious being methotrexate-related lymphoproliferative disorder.While this may occur in various organs,liver involvement is rare.Information on these liver lesions,including clinical characteristics,course,and imaging studies,has not been summarized to date.CASE SUMMARY We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain.She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate.Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3,CD4,CD8,and CD79a but negative for CD20 and CD56.Staining for Epstein-Barr virus-encoded RNA was negative.And based on these findings,the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders.A timedependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses.CONCLUSION The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.
